MEDICAL Gift of Panajna-Pacific Intern 1 Exposition Company. TEXT-BOOK or HUMAN PHYSIOLOGY TEXT-BOOK OF HUMAN PHYSIOLOGY INCLUDING HISTOLOGY AND MICROSCOPICAL ANATOMY WITH ESPECIAL REFERENCE PRACTICE OF MEDICINE DR. bf LANDOIS FKOFESSOR OF PHYSIOLOGY AND DIRECTOR OF THE PHYSIOLOGICAL INSTITUTE IN THK UNIVERSITY OF GKEIFSVVALD TENTH REVISED AND ENLARGED EDITION EDITED BY , ALBERT P. . GY M4< ^GUtT-lk IN\Tl4*E ANIA COLLEGE OF DENTAL IN THE r'tBXn.*:. inSTITUTE OF 1 ART r "S?MrWcE'AM> IMHSIK-v, IHILA :' :. ' --.- r : v ,r:- : - I-KOFKSSOK OF PHYSIOLOGY M4< ^GUtT-lk IN\Tl4*E OTMSfelp^c^kKf;*: ; PROFESSOR OF PHYSIOLOGY IN THE PENNSYLVANIA COLLEGE OF DENTAL SURGERY ; LECTURER ON PHYSIOLOGY AND HYGIENE DELPHIA TRANSLATED BY AUGUSTUS A. ESHiNER, M.D. FRDFESSOR OF CLINICAL MHUICINE IN T^ KiLADE|miArFC,Y( I IM' : I'1I\^I IAN TO THE PHILADELPHIA HOSPITAL; Assi ICINE IN T^ iyLADE|miArFC,Y( I IM' : I'1I\^I IAN TO THE P iSir4T PH.gA(ULm. to imM. PHM ADI 1.1 m.\ )-w ?>< L. LANDOIS. TABLE OF CONTENTS. INTRODUCTION. The Scope and Aim of Physiology and its Relation to Allied Branches of Physical Science, 17 Matter, 18 Forces, 19 Law of the Constancy of Energy, 23 Animals and Plants, 25 Kinetic Energy and Life, 28 PHYSIOLOGY OF THE BLOOD. Physical Properties of the Blood, 29 Microscopic Examination of the Blood, 31 The Red Blood-corpuscles (Erythrocytes) , 34 Preservation of Red Blood-corpuscles, 36 Permeability of Erythrocytes. Isotonia (Hyperisotonia and Hypisotonia) . Demonstration of the Stroma. Lake coloration of the Blood, 37 Form, Size, and Number of Erythrocytes in Different Animals, 40 Development of Red Blood-corpuscles, 41 Destruction of Red Blood-corpuscles, 43 The White Blood-corpuscles (Leukocytes) , the Blood-plates and Elementary Granules, 45 Abnormal Changes in the Red and White Blood-corpuscles, 50 Chemical Constituents of the Red Blood-corpuscles, 51 Preparation of Hemoglobin-crystals, 52 Quantitative Estimation of the Hemoglobin _ 52 Employment of the Spectroscope for Hemoglobin Examination; Oxygen- combinations of Hemoglobin: Oxyhemoglobin and Methemoglobin, ... 55 Carbon-monoxid Hemoglobin and Carbon-monoxid Poisoning, 58 Other Hemoglobin-combinations, 59 Decomposition of Hemoglobin, 60 Hemin (Hematin Chlorid) ; Identification of Blood by Means of the Hemin- test, 61 Hematoidin, 63 The Colorless Proteid of Hemoglobin, 63 Proteid Bodies in the Stroma 63 Remaining Constituents of the Red Blood-corpuscles, 64 Chemical Constituents of the Leukocytes, 64 The Blood-plasma and Its Relation to the Serum, 65 Fibrin: Its General Properties; Coagulation, 65 General Phenomena Attending Coagulation, 67 Nature of Coagulation, 68 Source of the Fibrinogenous Substances, 70 Relations of the Red Blood-corpuscles to Fibrin-formation, 71 Chemical Constitution of the Blood-plasma and the Serum, 72 THE GASES OF THE BLOOD. Absorption of Gases by Solid Bodies and by Fluids, 74 Diffusion of Gases: Absorption of Gaseous Mixtures, 75 Separation of the Gases of the Blood, 7 6 Quantitative Estimation of the Gases of the Blood, 77 Special Facts Concerning the Gases of the Blood 78 xi Xll TABLE OF CONTENTS. . PAGE As to the Presence of Ozone in the Blood, 79 Carbon Dioxid and Nitrogen in the Blood, 80 Estimation of the Individual Constituents of the Blood, 81 Arterial and Venous Blood, 82 The Amount of Blood : 83 Abnormal Increase in the Amount of Blood or of Its Individual Parts, .... 84 Abnormal Diminution in the Amount of Blood or of Its Individual Con- stituents, 86 PHYSIOLOGY OF THE CIRCULATION. Cause, Purpose, Division, 88 The Heart, . 89 Arrangement of the Muscle-fibers of the Heart and Their Physiological Sig- nificance, 89 Arrangement of the Musculature of the Ventricles, 90 Pericardium; Endocardium; Valves, 91 The Coronary Vessels; Automatic Regulation, Nutrition, and Isolation of the Heart 93 The Movements of the Heart. Variations in Tone, 96 Pathological Disturbance of the Function of the Heart, 99 The Apex-beat. The Cardiogram, 100 The Time-relations of the Movements of the Heart, 104 Pathological Variations in the Heart-beat, 107 The Heart-sounds, no Abnormalities in the Heart-beat, 112 Duration of the Movement of the Heart, 113 The Cardiac Nerves, 114 Irritability of the Automatic Motor Centers in the Heart and of the Heart- Muscle 115 The Cardiopneumatic Movement, 121 Influence of the Respiratory Pressure on the Dilatation and Contraction of the Heart, 122 THE MOVEMENT OF THE BLOOD IN THE CIRCULATION. Toricelli's Theorem on the Velocity of Escape of Fluids, 125 Propelling Force, Velocity and Lateral Pressure, 126 Movement through Capillary Tubes, 128 Continuous and Undulatory Movement in Elastic Tubes, 128 Structure and Properties of the Blood-vessels, . . . 129 Pulse-movement. Technic of Pulse-examination, 133 The Pulse-tracing, the Recoil-elevation and the Elasticity-elevations, 138 The Dicrotic Pulse 142 Differences in the Time-relations of the Pulse, 143 Variations in the Strength, the Tension, and the Volume of the Pulse, 145 Sphygmographic Tracings from Different Arteries, 146 Phenomena of Anacrotism, 147 Influence of the Respiratory Movements on Sphygmographic Tracings, .... 149 The Influences of Pressure on the Shape of Sphygmographic Tracings, 152 Velocity of Propagation of Pulse-waves, 153 Propagation of Pulse-waves in Rubber Tubes, 153 Propagation- velocity of the Pulse-waves in Man, 154 Other Pulsatory Phenomena, 156 Vibration of the Body Due to the Action of the Heart and the Course of the Blood-waves, 157 The Movement of the Blood, 158 Schematic Reproduction of the Circulation, 160 Capacity of the Ventricles, 161 Methods for Measuring the Blood-pressure, 162 The Blood-pressure in the Arteries, 165 The Blood-pressure in the Capillaries, 168 The Blood-pressure in the Veins, 169 The Blood-pressure in the Pulmonary Artery, 169 Measurement of the Velocity of the Blood-current , 171 TABLE OF CONTENTS. xiii The Velocity of the Current in the Arteries, Capillaries, and Veins, ...... 1*7*5 Estimation of the Capacity of the Ventricles from the Current-velocity by the Method of Carl Vierordt, ................................. ... I7 6 The Duration of the Circulation,. ... I77 The Work of the Heart, ......................... '.'.'.'.'.'.'.'.'.'.'.'.'.'.'.}'.'.'.-. 178 The Movement of the Blood in the Smallest Vessels, ..................... 178 The Migration of the Blood-corpuscles from the Vessels; Stasis; Diapedesis, 180 The Movement of the Blood in the Veins, ....................... 182 Sounds and Murmurs in the Arteries, .................................. 183 Acoustic Phenomena within the Veins, ................................. 184 The Venous Pulse. The Phlebogram, ................................. 185 The Distribution of the Blood, ....................... !88 Plethysmography, .................................................. X 8 9 Transfusion of Blood, ................................................ X Q O The Ductless Glands. Internal Secretions, ............................. 193 Comparative ............ ............................................ jgS Historical .......................................................... X PHYSIOLOGY OF RESPIRATION. Objects and Subdivisions, ............................................ 201 Structure of the Air-passages and the Lungs, ........................... 201 Mechanism of the Respiratory Movements. Abdominal Pressure, ......... 204 Respiratory Volumes, ............................................... 205 The Rate of Respiration, ............................................ 207 The Time Relations of Respiratory Movements. Pneumatography ........ 207 Types of Respiratory Movements, ..................................... 210 Pathological Variations in the Respiratory Movements, .................. 210 Summary of the Muscular Mechanism Concerned in Inspiration and Ex- piration, ...................................................... 2 12 Action of the Individual Respiratory Muscles, .......................... 213 Dimensions and Expansibility of the Thorax, ........................... 217 Respiratory Excursion of the Lungs, ................................... 218 Variations from the Normal Percutory Conditions in the Thorax, ......... 220 The Normal Respiratory Sounds, ..................................... 221 Pathological Respiratory Sounds, ..................................... 222 Pressure in the Air-Passages during Respiration, ........................ 223 Mouth-breathing and Nasal-breathing, ................................. 224 Modified Respiratory Acts, ........................................... 225 Chemistry of Respiration, .................................. 226 Quantitative Estimation of the Carbon Dioxid, the Oxygen, and the Aqueous Vapor in Gaseous Mixtures, ...................................... 226 Methods of Investigation, ............................................ 227 Composition and Properties of Atmospheric Air, ........................ 229 Composition of Expired Air, .......................................... 231 Extent of the Daily Interchange of Gases, .................. ... 232 Factors Influencing the Extent of the Respiratory Exchange of Gases, . . 232 Diffusion of Gases within the Respiratory Organs ....................... 237 Interchange of Gases between the Blood in the Pulmonary Capillaries and the Air in the Alveoli, ............................. ... 238 The Respiratory Gaseous Exchange as a Dissociation Process.. . 240 Cutaneous Respiration, .............................. 241 Internal Respiration or Tissue-respiration, ............................. 241 Respiration in a Closed Space, or with Artificial Changes in the Amounts of Oxygen and Carbon Dioxid in the Respired Air, ...... 244 Respiration of Foreign Gases, .............. 245 Other Injurious Substances in the Inspired Air ................. 245 Renewal of the Air in Living-rooms (Ventilation). Examination of tin- Air, 246 Normal Secretion of Mucus in the Air-passages. The Expectoration (Sputum) , ............................................ 249 Effects of Atmospheric Pressure, ...................................... 251 Comparative. Historical, ......................................... 254 XIV TABLE OF CONTENTS. PHYSIOLOGY OF DIGESTION. PAGE The Mouth and Its Glands, 256 The Salivary Glands, , 257 The Secretory Activity of the Salivary Glands, 259 The Nerves of the Salivary Glands, 259 The Influence of the Nervous System on the Secretion of Saliva, 260 The Saliva from the Individual Glands, 262 The Mixed Saliva, the Secretion of the Mouth, 263 Physiological Actions of the Saliva, 264 Tests for Sugar, 267 Quantitative Estimation of Sugar, 268 The Mechanics of the Digestive Apparatus, 270 The Prehension of Food, 270 The Movements of Mastication, 270 Structure and Development of the Teeth, 272 Movements of the Tongue, 276 The Act of Swallowing (Deglutition) , '. 277 The Movements of the Stomach. Vomiting, 280 The Movements of the Intestines, 282 The Evacuation of Feces (Defecation), 283 Nervous Influences Affecting the Intestinal Movements, 286 The Structure of the Gastric Mucous Membrane, 289 The Gastric Juice, 292 The Secretion of the Gastric Juice, 293 Methods of Obtaining the Gastric Juice. The Preparation of Artificial Digestive Fluids; Demonstration and Properties of Pepsin, 295 The Process and the Products of Gastric Digestion, 297 The Gases of the Stomach, 301 Structure of the Pancreas, 302 T.he Pancreatic Juice, 303 The Digestive Activity of the Pancreatic Juice, 304 The Secretion of the Pancreatic Juice, 307 The Structure of the Liver, 308 Chemical Constituents of the Liver-cells, \ 311 Diabetes Mellitus, 313 The Constituents of the Bile, 315 Secretion of Bile, 319 Excretion of Bile, 321 Resprption of Bile, 322 Action of the Bile, 324 Final Fate of the Bile in the Intestinal Canal, 325 The Intestinal Juice, 326 Fermentative Processes in the Intestines Due to Microbes; Intestinal Gases, 329 Processes in the Large Intestine. Formation of the Feces, 335 Morbid Alterations in Digestive Activity, 339 Comparative Physiology of Digestion, 343 Historical, 346 PHYSIOLOGY OF ABSORPTION. Structure of the Organs of Absorption, 348 Absorption of the Digested Food, 351 Absorptive Activity of the Wall of the Alimentary Canal, 354 Influence of the Nervous System, 359 Nourishment by Means of "Nutritive Enemata," 359 System of Lacteal and Lymphatic Vessels, 360 Origin of the Lymph-channels. Lymphatics 361 The Lymph-glands, 363 Properties of the Chyle and the Lymph, 366 Quantitative Relations of Lymph and Chyle, 368 Origin of Lymph, 369 Circulation of Chyle and Lymph, 371 Absorption of Parenchymatous Effusions, 373 Lymph-stasis and Serous Effusions, 374 TABLE OF CONTENTS. XV PAGE Comparative 375 Historical, 375 PHYSIOLOGY OF ANIMAL HEAT. Sources of Heat 377 Animals with Constant and with Variable Temperature, 381 Methods of Estimating the Temperature: Thermometry, 382 Temperature-topography, 385 Influences Affecting the Temperature of Individual Organs, 387 Measurement of the Volume of Heat: Calorimetry, 389 Heat-conduction of Animal Tissues. Expansibility of Animal Tissues by Heat, 390 Variations in the Mean Bodily Temperature, 391 Regulation of the Temperature, 394 Heat-balance, 399 Variations in Heat-production, : 400 Relation of Heat-production to the Work Performed by the Body, 400 Accommodation to Variations in Temperature, 402 Accumulation of Heat in the Body, 403 Fever, 404 Artificial Elevation of the Bodily Temperature, 406 Employment of Heat, 407 Post-mortem Elevation of Temperature, 407 The Influence of Cold upon the Body, 408 Artificial Reduction of the Bodily Temperature in Animals, 409 Employment of Cold, 411 The Temperature of Inflamed Parts 411 Historical. Comparative 41 * PHYSIOLOGY OF METABOLISM. Scope of Metabolism, 413 SYNOPSIS OF THE MOST IMPORTANT SUBSTANCES USED AS FOOD. Water. Examination of Drinking-water 413 Structure and Secretory Activity of the Mammary Glands, 417 Milk and Milk-preparations, 4*9 Eggs, ; 423 Meat and Meat-preparations, 4 2 3 Vegetable Foods, 426 Condiments: Coffee, Tea, Chocolate, Alcoholic Drinks and Spices, 428 PHENOMENA AND LAWS OF METABOLISM. Metabolic Equilibrium, 43 Metabolism in the State of Starvation, 439 Metabolism with an Exclusive Diet of Meat, Albumin or Gelatin 442 An Exclusive Diet of Fats or Carbohydrates, 443 Laws Governing Metabolism on a Mixed Diet of Meat and Fat or Carbohy- drates, 443 Origin of the Fat in the Body, 444 Deposition of Fat and Flesh in the Body (Hypernutrition) . Corpulence and the Means for its Correction, 445 The Metabolism of the Tissues, 44$ Regeneration, 45 I Transplantation and Adhesion, 454 Increase in Size and in Weight in the Process of Growth, 455 SUMMARY OF THE CHEMICAL CONSTITUENTS OF THE ORGANISM. Inorganic Constituents, 45 6 Organic Constituents. The Proteid Bodies or Protein-Substances. The True Albuminous Bodies, 457 The Albuminoid Bodies, Nitrogenous Glucosids, 462 XVI TABLE OF CONTENTS. PAGE Nitrogenous Pigments, 462 Organic Non-nitrogenous Acids, 462 The Fats, 462 The Alcohols, 464 The Carbodyhrates, 464 Ammonia-derivatives and Their Combinations, 467 Aromatic Bodies, 468 Historical 468 THE SECRETION OF URINE. Structure of the Kidney, 469 The Urine. The Physical Characters of the Urine, 472 THE ORGANIC CONSTITUENTS OF THE URINE. Urea, 475 Qualitative and Quantitative Estimation of Urea, 478 Uric Acid, -.-. 479 Qualitative and Quantitative Estimation of Uric Acid, 482 Kreatinin, Xanthin-bases, Oxaluric, Oxalic, and Hippuric Acids, 482 Coloring-matters of the Urine, 485 Substances Forming Indigo, Phenol, Kresol, Pyrocatechin , and Skatol. Other Substances, 487 THE INORGANIC CONSTITUENTS OF THE URINE. Spontaneous Alterations in the Urine on Standing; Acid and Ammoniacal Urinary Fermentation, 493 Albumin in the Urine: Protein uria, Albuminuria, 494 Blood and Hemoglobin in the Urine: Hematuria, Hemoglobinuria 497 Biliary Constituents in the Urine: Choluria, 500 Sugar in the Urine: Glycosuria, 501 Cystin, 503 Leucin and Tyrosin, 503 Sediments in the Urine, 503 Schematic Resume for the Recognition of all of the Sediments in the Urine, 506 Urinary Concretions, 507 The Physiological Process of Urinary Secretion, 509 The Preparation of the Urine, 513 The Passage of Various Substances into the Urine, 514 Influence of the Nerves upon the Secretion of the Kidneys, 514 Uremia; Ammoniemia; Uric-acid Dyscrasia, 516 Structure and Functions of the Ureters, 517 Structure of the Urinary Bladder and the Urethra, 519 Collection and Retention of the Urine in the Bladder. Evacuation of the Urine 520 Morbid Derangement of Urinary Retention and of Micturition, 523 Comparative. Historical, 524 FUNCTIONS OF THE EXTERNAL INTEGUMENT. Structure of the Skin, 525 The Nails and the Hair, 527 The Glands of the Skin, 531 The Skin as an External Covering, 532 Cutaneous Respiration. Cutaneous Secretion. Sebum. Sweat. Pigment- formation, 533 Influences Affecting the Secretion of Sweat ; Nervous Control Affecting the Secretion of Sweat, 536 Nervous Control Affecting the Secretion of Sweat, 536 Physiological Care of the Skin. Pathological Abnormalities in the Secre- tion of Sweat and Sebum, 538 Absorption through the Skin. Galvanic Conductivity, 539 Comparative. Historical, * 540 TABLE OF CONTENTS. Xvii PHYSIOLOGY OF THE MOTOR APPARATUS. PAGE Structure and Arrangement of the Muscles, 542 Physical and Chemical Properties of Muscular Tissue, 547 Metabolism in Muscle. The Source of Muscular Energy, 549 Muscular Rigidity (Cadaveric Rigidity, Rigor Mortis) 552 Irritability, Stimulation, and Death of the Muscle, 555 Change of Shape in Active Muscle 558 The Time-relations of Muscular Contraction. Myography. Simple Con- traction. Tetanus. Isotony. Isometry, 560 Rapidity of Propagation of Muscular Contraction 568 Muscular Work, _ 569 The Elasticity of Passive and Active Muscle. Myotonometry, 572 Heat-production in Active Muscle, 576 The Muscle-murmur, 578 Fatigue of Muscle, 579 Mechanism of the Bones and Their Attachments, 581 Arrangement and Function of the Muscles in the Body, 583 Gymnastic Exercises and Therapeutic Gymnastics. Pathological Varia- tions in the Motor Functions 587 SPECIAL MOVEMENTS. Standing, 589 Sitting, _ 592 Walking, Running, Jumping, 592 Comparative Study of Motion, 596 VOICE AND SPEECH. Scope of the Voice. Preliminary Physical Considerations Concerning the Production of Sound in Reed-apparatus 599 Arrangement of the Larynx 600 Examination of the Larynx 606 Conditions Influencing the Sounds of the Vocal Apparatus, 609 Range of the Voice, 6 10 Speech. The Vowels, 6 1 1 The Consonants, 615 Pathological Variation in Voice and Speech,. . . 617 Comparative. Historical, 618 GENERAL PHYSIOLOGY OF THE NERVOUS SYSTEM AND ELECTRO-PHYSIOLOGY. General Conception of the Nervous System. Structure and Arrangement of the Elements of the Nervous System, , 621 Cheniistry of Nervous Tissue. Mechanical Properties of Nerves, 626 Metabolism in Nerves, 628 Irritability of Nerves. Stimuli 629 Diminished Irritability; Death of the Nerve. Nerve-degeneration and Nerve-regeneration, 633 ELECTRO-PHYSIOLOGY. Preliminary Physical Considerations. The Galvanic Current. Electro- motors. Conduction-resistance. Ohm's Law. Conduction through Animal Tissues. The Rheocord, : 638 The Action of the Galvanic Current upon the Magnetic Needle. The Multi- plicator, . 6 4 J Electrolysis. Transition-resistance. Galvanic Polarization. Batteries and Unpolarizable Electrodes. Internal Polarization of Moist Conductors. Cataphoric Action of the Galvanic Current. Sec- ondary Resistance, ; 643 Induction. The Extra Current. Magnetization of Iron by the Galvanic Current. Voltaic Induction. Unipolar Induction-effects. Magneto- induction, 645 XV111 TABLE OF CONTENTS. PAGE Du Bois-Reymond's Sliding Induction-apparatus. Pixii-Saxton's Magneto- induction Machine, 646 Electrical Currents in Resting Muscle and Nerve. Cutaneous Currents. Glandular Currents, 648 Currents of Stimulated Muscles and Nerves and of Secretory Organs, 652 Currents in Nerves and in Muscles in the Electrotonic State, 656 Theories and Currents in Muscles and Nerves, 657 Altered Irritability of Nerve and Muscle in Electrotonus 660 The Development and the Disappearance of Electrotonus. The Law of Contraction. The Law of Polar Stimulation, 663 Rapidity of Conduction of the Stimulus in Nerves, 667 Double Conduction in Nerves, 669 Employment of Electricity for Therapeutic Purposes. Degenerative Reac- tions of Muscle and Nerve, 669 Comparative. Historical, 675 PHYSIOLOGY OF THE PERIPHERAL NERVES. Classification of Nerve-fibers According to Function, 677 THE CEREBRAL NERVES. Olfactory Tract and Bulb, 678 Optic Nerve and Tract, 679 Oculomotor Nerve, 680 Trpchlear Nerve, 682 Trigeminal Nerve, 683 Abducens Nerve, 693 Facial Nerve, 694 Auditor}^ Nerve, 699 Glossopharyngeal Nerve, 703 Vagus Nerve 704 Accessory Nerve of Willis, 712 Hypoglossal Nerve, 713 The Spinal Nerves, 713 Sympathetic Nervous ^ System, 718 Comparative. Historical 721 PHYSIOLOGY OF THE NERVOUS CENTERS. General Considerations, 723 THE SPINAL CORD. The Structure of the Spinal Cord, 723 The Spinal Reflexes, 728 Inhibition of Reflexes, 731 Centers in the Spinal Cord, 734 Irritability of the Spinal Cord, 736 Conducting Paths in the Spinal Cord, 738 THE BRAIN. General Outline of the Structure of the Brain, 741 The Medulla Oblongata, 748 Reflex Centers in the Medulla Oblongata, 748 The Respiratory Center and the Innervation ;of the Respiratory Apparatus, 750 The Center for the Inhibitory Nerves (Diminishing the Frequency and the Strength) of the Heart and the Fibers Passing to the Vagus, 758 The Center for the Accelerator and Augmenting Cardiac Nerves and the Fibers to which it Gives Rise, 760 The Vasomotor Center and Nerves, 762 The Vasodilator Center and Nerves, 771 The Spasm-center. The Sweating Center, 773 Psychic Functions of the Cerebrum, 774 The Motor Cortical Centers of the Cerebrum 780 The Sensorial Cortical Centers, 785 TABLE OF CONTENTS. xix The Cortical Thermic Center, 788 Physiological Topography of the Surface of the Cerebrum in Man 791 The Basal Ganglia of the Cerebrum, The Midbrain. Forced Movements. Other Cerebral Functions, 802 Functions of the Cerebellum, 807 Protective and Nutritive Apparatus of the Brain 809 Comparative. Historical, 811 PHYSIOLOGY OF THE ORGANS OF SPECIAL SENSE. Introductory Remarks 813 THE VISUAL APPARATUS. Preliminary Anatomical and Histological Observations. The Intraocular Pressure, 815 Preliminary Dioptric Considerations, 823 Application of Dioptric Laws to the Eye. Construction of the Retinal Image. The Ophthalmometer. Erect Images, 829 Accommodation of the Eye, 83 1 Refractive Power of the Normal Eye. Anomalies of Refraction, 835 Measure of the Power of Accommodation, 837 Spectacles, 839 Chromatic and Spherical Aberration. Defective Centering of the Refracting Surfaces. Astigmatism 840 The Iris, 841 Entoptic Phenomena. Subjective Optical Manifestations 844 Illumination of the Eye, and the Ophthalmoscope, 847 The Function of the Retina in Vision, 850 Perception of Colors, 856 Color-blindness: Its Practical Importance, 860 Time-relations of Retinal Stimulation. Positive and Negative After- images. Irradiation. Contrast, 862 Ocular Movements and Ocular Muscles, 866 Binocular Vision, 870 Single Vision. Identical Retinal Points. Horopter. Suppression of Double Images, 871 Stereoscopic Vision. Judgment of Solidity, 873 Estimation of Size and of Distance. False Estimates of Size and Direction, 877 Organs for the Protection of the Eye 879 Comparative. Historical, 881 THE AUDITORY APPARATUS. Plan of the Structure of the Ear, 885 Preliminary Physical Considerations, ... 886 Auricle. External Auditory Canal, 887 The Tympanic Membrane, 888 The Auditory Ossicles and Their Muscles 890 Eustachian Tube. Tympanic Cavity 894 Sound-conduction in the Labyrinth, 896 Structure of the Labyrinth and the Terminations of the Auditory Nerve, . . 897 Quality of Auditory Perceptions. Perception of the Pitch and Intensity of Tones, 899 Perception of Timbre. Analysis of Vowels, . 903 Function of the Labyrinth in the Act of Hearing, 907 Simultaneous Action of Two Tones. Harmony. Beat. Discord. Differ- ential Tones and Summation -tones, 908 Auditory Perception. Fatigue of the Ear. Objective and Subjective Hearing. Associated Sensations. Auditory After-sensations. .. 910 Comparative. Historical, 9 12 THE OLFACTORY APPARATUS. Structure of the Olfactory Apparatus 913 Sensation of Smell, . 9i4 XX TABLE OF CONTENTS. THE GUSTATORY APPARATUS. Situation and Structure of the Organs of Taste 916 Gustatory Sensations, 917 THE TACTILE APPARATUS. Terminations of the Sensory Nerves, 920 Sensory and Tactile Sensations, 922 Sense of Space, 924 The Pressure-sense, 927 The Temperature-sense, . . 930 Common Sensation. Pain, 934 The Muscular Sense. Power-sense, 936 PHYSIOLOGY OF REPRODUCTION AND DEVELOPMENT. Varieties of Generation, 938 The Seminal Fluid, 942 The Ovum, 946 Puberty, . 951 Menstruation, 951 Erection, 955 Ejaculation. Reception of the Seminal Fluid, . . 957 Impregnation of the Ovum, 958 Cleavage, Morula, Blastula, Gastrula, Formation of the Germinal Layers. First Rudiments of the Embryo, 961 Formations from the Epiblast, 966 Formations from the Hypoblast and the Mesoblast, 969 Folding Off of the Embryo. Formation of the Heart and the First Circu- lation, 970 Further Development of the Body, 972 Formation of the Amnion and the Allantois, 974 Human Fetal Membranes. Placenta. Fetal Circulation, 975 Chronology of Human Development. Fetal Movements, 980 Development of the Osseous System, 983 Development of the Vascular System, 990 Development of the Alimentary Canal, 993 Development of the Urinary and Sexual Organs, . . 995 Development of the Central Nervous System, 1000 Development of the Organs of Special Sense, 1001 Parturition, 1002 Comparative. Historical, 1004 LIST OF ILLUSTRATIONS. FIG. p AGE 1. Human and Amphibian Colored Blood-corpuscles 32 2. Apparatus of Abbe and Zeiss for Counting the Corpuscles 33 3. The Melangeur Pipet or Mixer, 33 4. Red Blood-corpuscles, 34 5. Formation of Red Blood-corpuscles within " Vaso-formative Cells," from the Omentum of a Rabbit Seven Days Old, 42 6. White Blood-corpuscles of Man and Frog, 45 7. Human Leukocytes, showing Ameboid Movements, 47 8. Various Forms of Leukocytes and Erythrocytes, 48 9. " Blood-plates" and their Derivatives, 49 10. Hemoglobin-crystals, 52 1 1 . V. Fleischl's Hemometer, 53 1 2 . Diagrammatic Representation of the Spectroscope for Study of the Ab- sorption-spectra of the Blood, 55 13. 14. The Absorption-spectra of Oxyhemoglobin, and of Gas- free Hemo- globin with Increasing Concentration, 56 15. The Various Absorption-spectra of Hemoglobin, 57 1 6. The Absorption-spectra of Hematoporphyrin, 60 1 7 . Hemin-crystals 62 1 8. Hemin-crystals Prepared from Blood-stains, 62 19. Hematoidin-crystals 63 20. Diagrammatic Representation of Pfluger's Pump for the Extraction of the Gases of the Blood, 77 21. Diagrammatic Representation of the Circulation, 88 22. Course of the Muscle-fibers in the Left Auricle (Joh. Reid). Distribu- tion of Transversely Striated Muscle-fibers on the Superior Vena Cava (Flischer), 90 23. Course of the Muscle-fibers in the Ventricles (C. Ludwig) , 91 24. Semilunar Valves Closed and Opened, 93 2 5 . Diagrammatic Representation of the Auricular Systole with Ventricular Diastole, and of Auricular Diastole with Ventricular Systole, 96 26. Plaster Cast of the Ventricles of the Human Heart, Viewed from Behind and Above, 98 27. The Closed Pulmonary Semilunar Valves of Man, Viewed From Below, . 99 28. Curves of the Apex-beat, 101 29. Changes of the Heart during Systole, and Sections of the Thorax, 102 30. Contraction-curves from the Ventricle of a Rabbit Registered on a Plate Attached to a Vibrating Tuning-fork, 105 3 1 . Curves Showing the Movements of the Separate Portions of the Heart (Chauveau and Marey) , 1 06 32. Simultaneous Record Showing Cardiogram, the Curve of the Ventric- ular Pressure and that of the Aortic Pressure from the Dog (K. Hurihle) , 107 33. Various Forms of Pathological Apex-beat Curves, 109 34. Topography of the Thorax and of the Thoracic Viscera (v. Luschka and v. Dusch) , in 35. Landois' Cardiopneumograph, and Cardiopneumatic Curves Obtained with its Aid, 122 36. Apparatus for the Demonstration of the Influence of Respiratory Ex- pansion and Contraction of the Thorax on the Heart and the Cir- culation, 124 37. Pressure-vessel Filk'm- tner) , 94 XXV111 LIST OF ILLUSTRATIONS. FIG. PAGE 352. Heads of Taenia solium and Tcenia mediocanellata and Mature Pro- glottids of Each 941 353. Seminal Crystals, 942 354. Spermatozoa, 943 355. Spermatogenesis (semidiagrammatic) , 945 356. A Fresh Ovum from the Ovary of a Woman Thirty Years Old, 947 357. Mature Rabbit Ovum (Waldeyer) , 948 358. Ovary and Polar Globules, 949 359. Diagrammatic Representation of a Mesoblastic Ovum (Waldeyer), 950 360. White and Yellow Yolk-globules 950 361. Diagrammatic Longitudinal Section of a Hen's Egg, 950 362. The Ovary and the Fallopian Tube (Henle) , 952 363. Sagittal Section through the Normal Endometrium, Together with a Portion of the Contiguous Muscular Layer, 953 364. Horizontal Section of the Normal Endometrium (Orthmanri), 953 365. Fresh Corpus luteum (Balbiani) , 953 366. Lutein-cells from the Corpus luteum of the Cow (His) , 954 367. Corpus luteum of the Cow, enlarged one and one-half times (His) , 954 368. Anterior Pelvic Wall with the Urogenital Diaphragm (Henle), 956 369. Ovum of Scorpaena scrofa, ; 959 370. Ovum of a Starfish (asteracanthion) , 959 371. Four Stages of Division of an Impregnated Ovum of Echinus saxatilis, 960 372. Development of the Hypoblast (Kupffer) , 962 373. Ovum of the Rabbit (van Beneden) ...... 963 374. Germinal Plate of Bird's Egg, 964 375. Stages of Nuclear Division (Rabl) , 965 376. Schemata of Development, ._ 967 377. Lateral View of the Brain of a Human Embryo (His) , 968 378. Scheme of the Formation of the Chorda and the Coelom through Eva- gination of the Hypoblast, 970 379. Isolated Portion of Villi from a Human Placenta, 977 380. Section through the Uterus and the Attached Placenta at the Thirtieth Week (Ecker), 978 381. Left-sided Hare-lip, 985 382. Formation of the Face and Developmental Defects of the Face, 986 383. Ossification of the Innominate, 988 384. Development of the Heart (in part diagrammatic), 990 385. Development from the Aortic Arches, 991 386. Veins of the Embryo, 992 387. Development of the Veins of the First and the Second Circulation, and of the Portal System, 993 388. Development of the Intestine, 994 389. Development of the Lungs, 994 390. Development of the Great Omentum, 994 391. Transverse Section through the Primitive Kidney, the Rudimentary Duct of Muller, and the Sexual Gland in a Chick at the Fourth Day (Waldeyer) , 996 392. Development of the Internal Organs of Generation, 997 393. Development of the External Genitalia, 998 394. Development of the Eye, 1001 INTRODUCTION. THE SCOPE AND AIM OF PHYSIOLOGY AND ITS RELATION TO ALLIED BRANCHES OF PHYSICAL SCIENCE. Physiology is the science of the vital phenomena of organs, or, briefly, the study of life. In accordance with the classification of organisms the following divisions are made, namely, Animal Physiology, Vegetable Physiology, and the Physiology of the Lowest Forms of Life, which occupy the boundary between animals and plants, the protists, micro- organisms or microbes, and the elementary organisms or cells occupying the same plane. It is the aim of physiology to establish these phe- nomena, to determine their regularity and their causes, and to correlate these with the general fundamental laws of natural science, especially those of physics and chemistry. The relation of physiology to allied branches of natural science is shown in the following scheme : BIOLOGY, The science of organized beings or organisms (animals, plants, protists, and ele- mentary organisms). MORPHOLOGY. The study of the form of organisms. General Morphology. Special Morphology. The study of the formed elementary The study of the parts and organs constituents of organisms (Histology) : of organisms (Organ ology, Anatomy) : (a) Histology of plants. (a) Phytotomy. (b) Histology of animals. (b) Zootomy. PHYSIOLOGY. The study of the vital phenomena of organisms. General Physiology. Special Physiology. The study of vital phenomena in The study of the functions of indi- general: vidual organs: (a) Of plants. (a) Of plants. (b) Of animals. (b) Of animals. EMBRYOLOGY. The study of the generation and development of organisms. Morphologic division i . Developmental his- Physiologic division of the study of develop- tory of the individual of the study of develop- being (for instance, man) from its germ, germinal history (Ontogeny): (a) In plants. (6) In animals. 2. Developmental his- tory of entire species of organisms, from the low- est forms of creation up- ward, family history (Phytogeny) : (a) In plants. (b) In animals. 17 ment, that is, the study of the conformation at dif- ferent stages of develop- ment: (a) General. (6) Special. ment, that is, the study of functional activity during development: (a) General. (b) Special. 1 8 MATTER. If it be desired to give a special position in the system of organisms to those beings that occupy the lowest plane of development and that, representing to a cer- tain degree the prototype in the family history, have as yet not been differentiated into animal and vegetable, the so-called protists (Haeckel), these likewise would occupy a distinct place in the foregoing arrangement by the side of animals and plants. Morphology and physiology are coordinate branches of biology. A knowledge of morphology is a prerequisite for the comprehension of physiology, inasmuch as the functions of an organ can be correctly understood only if its external form and its internal structure are pre- viously known. The developmental history occupies an intermediate position between morphology and physiology. It is a department of morphology in so far as it has to do with a description of the parts of the developing organism ; it is a physiologic study in so far as it investi- gates the functions and vital phenomena during the period of develop- ment of the organism. In all the branches of biologic science it is neces- sary to enter upon a consideration of physical and cbemical principles. MATTER. The entire visible world, including all organisms, consists of matter, that is, of the material or substance that occupies space. A distinction is made between ponderable matter (in ordinary language often desig- nated simply matter), which can be weighed upon the scales; and im- ponderable matter, which cannot be weighed upon the scales. The latter is designated ether (also luminiferous ether or light-ether). Ponderable matter or bodies possess form (or shape), that is, the outline of their limit- ing surfaces; also volume, that is, the amount of space they occupy; and finally an aggregate condition, which takes a solid, liquid, or gaseous form. The ether fills the space of the universe, at any rate, with certainty to the most remote visible stars. This light-ether, notwithstanding its imponderability, possesses quite definite mechanical properties. It is infinitely more attenuated than any other known form of gas, and never- theless its behavior corresponds rather with that of a solid body than with that of a gas. It more nearly resembles a gelatinous mass than air. It takes part in the vibrations of the atoms of the most distant stars associated with the luminous phenomena of the latter, and it is thus the carrier of light, which through its vibrations it conducts to the visual apparatus with inconceivable rapidity (300,000 kilometers in the second). Imponderable matter (ether) and ponderable matter (substance) are not sharply delimited from each other; on the contrary, the ether pene- trates the interstices present in the smallest particles of ponderable matter. If ponderable matter be conceived to be divided into gradually smaller and smaller parts, in the process of progressive subdivision parts would eventually be reached whose aggregate condition would still be recognizable. These are designated particles. Particles of iron would still be recognized as solid, those of water as fluid, and those of oxygen as gaseous. If it be conceived that the process of division of the parti- cles be carried to a further degree, a point will finally be reached beyond which further division cannot be effected either by mechanical or by physical means. In this way the molecule is obtained. A molecule, MATTER. 19 accordingly, is the smallest portion of a body that is capable of existence in a free state, and that, further, as a unit no longer exhibits the aggre- gate condition. The molecule is, however, not the ultimate unit of the body. On the contrary, every molecule consists of a collection of the smallest units, which are known as atoms. An atom is incapable of occurring alone in a free state, but atoms unite with other atoms of the same or of different character to form atom-complexes, desig- nated molecules. Atoms are unconditionally insusceptible of division; whence the name. Atoms, further, are conceived to be of constant size and solid in themselves. From the chemical standpoint the atom of an elementary body (element) is the smallest amount of an element that is capable of entering into chemical combination. Just as ponderable matter consists in its ultimate parts of ponderable atoms, so also does the ether, imponderable matter, consist of analogous particles of smallest size, namely, ether-atoms. Within ponderable matter the ponderable atoms are arranged in quite a definite order with relation to the ether-atoms. The ponderable atoms are drawn mutually toward one another (attraction) ; the pon- derable atoms likewise attract the imponderable atoms; but the ether- atoms mutually repel one another. It thus comes about that in the ponderable mass ether-atoms are collected about every ponderable atom. These collections, designated "dynamids" by Redtenbacher, tend, in accordance with the powers of attraction of the ponderable atoms, to approach one another, but only so far as permitted thus to do by the repellent power of the surrounding ether-atoms. Therefore the pon- derable atoms can never cohere without interstices, but the entire mass of matter must be considered as loose in texture in consequence of the interposed ether-atoms, which prevent immediate contact between pon- derable atoms. The aggregate condition of the body depends therefore upon the mutual arrangement of the molecules (namely, those small particles of matter that may still occur isolated in a free state). Within solid bodies, which are characterized by constancy of volume, as well as independence of form, the molecules are arranged in a fixed and unchangeable relation with one another. In fluid bodies, which are characterized by constancy of volume, though by variability of form, the molecules are in constant movement, just as in a mass of moving worms or insects the individual animals are incessantly changing their place with relation to one another. If this movement of the molecules attains such proportions that the individual molecules scatter in all directions (just as the moving collection of insects separates into its constituent parts), the body becomes gaseous, and is characterized in this form both by its inconstancy of form and its variability in volume. The study of molecules and their motor phenomena is the part of physics. FORCES. Gravitation; Work of a Force. All phenomena appertain to matter. They are the appreciable expression of the forces inherent in matter. The'forces themselves are not appreciable ; they are the causes of the phenomena. The first of the forces to be considered is gravita- tion. According to the law of gravitation every particle of ponderable matter in the universe attracts every other particle with a certain degree 2O FORCES. of force. This force diminishes inversely as the square of the distance between the two bodies. The power of attraction is further directly proportional to the quantity of the attracting matter, though without any relation to the quality of the body. The intensity of the force of gravitation can be measured by the extent of the movement that it communicates to a freely falling body previously supported in a vacuum but deprived of its support. This figure is 9.809, because the force of gravity operating for one second upon the freely falling body imparts to this a velocity of 9.809 meters. The final velocity of the freely falling body at the end of the first second (deter- mined experimentally) is designated thus, g = 9.809 meters. The velocity, v, of the freely falling body is in general proportional to the time, t, occupied in falling. Therefore v = gt (i) , that is, at the end of the first second v = g, i = g = 9.809 meters. The distance through which the body falls, s = ^t 2 (2) ; that is, the distance through which a body falls is as the square of the time occupied in falling. From (i) and (2) there follows (by eliminating t) v = \I 2 8 S ($}- The velocity is as the square root of the distance traversed in falling. v^ thus = s (4) A freely falling body, and also in general every mass in movement, possesses kinetic energy (actual energy) ; it is to a certain degree a reposi- tory of force. The kinetic energy of a body in movement is always equal to the product of its weight (determinable by scales) and the height to which it would rise from earth if it were raised from the earth with the velocity peculiar to it. If the kinetic energy of the moving body be designated W and its weight P, then W = P, s; then, from (4), W = P (5). The kinetic energy of a body is therefore proportional to the square of its velocity. If an accelerating force operating on a body ^(pressure, traction, or tension) drives it for some distance in the direction of its activity, the force thus expends work. This is equal to the product that is obtained if the amount of pressure or traction that propels the body is multiplied by the length of the path traversed. If K represents the pressure or the traction with which the force operates upon the body and S the path, then the work A = KS. In the same way the attraction between the earth and a body raised above it (as, for instance, a ram) is a source of work. It is customary to express the value of K in kilograms, but, on the other hand, that of S in meters. Accordingly the unit of work is the kilogrammeter (according to some the grammeter), that is, the force that is capable of raising i kilo (according to some i gram) to the height of i meter. Potential Energy. Transformation of Potential Energy into Kinetic Energy, and the Reverse. In addition to the kinetic energy referred to, bodies may possess also mechanical potential energy. By this' designation is understood an aggregation of forces that are still inhibited in their free evolution, and that, further, are causes of movement, without FORCES. 21 themselves being movement. The wound clock-spring prevented from unwinding by a catch, the stone resting upon the cornice of a tower, are illustrations of bodies possessing potential energy. Only an impulse is required to evolve actual from potential energy or to convert the poten- tial into kinetic energy. The stone resting upon the cornice of the tower was raised to that place by means of work (A). A = p, s, p representing the weight and s the height, p = m, g, thus the equivalent of the product of the mass (m) and the force of gravity (g) ; therefore A = m, g, s. This is at the same time the expression for the potential energy residing within the stone. This elastic energy may readily be converted into kinetic energy by causing the stone to fall from the edge of the tower by means of a slight push. The actual energy of the stone is equal to the terminal velocity with which it reaches the ground. = \/2~gs (see 3). v* = 2 gs mv 3 = 2ings m , v a = mgs m, g, s represents the potential energy residing within the stone at rest in its elevated position; v 2 is thus the kinetic energy correspond- ing to this potential energy. Actual energy and mechanical potential energy can be transformed into each other under most varied conditions; they can also be con- veyed from one body to another. Of the first statement the movement of a pendulum furnishes a striking illustration. The pendulum-bob, located at the highest point of the excursion, and which must be considered to be in a state of absolute rest at this point for a moment, is, exactly as the resting stone in the previous illustration, provided with potential energy. In the free movement that now takes place this potential energy is, converted into kinetic energy, which is greatest when the bob with greatest movement is in the vertical plane. Rising again from this point, the kinetic energy, with diminution in the free movement, is transformed into poten- tial energy, which again attains its maximum at the resting-point at the height of the excursion. In the absence of constantly operating resistances (resistance of the air, friction) this play of the alternate transformation of kinetic energy into potential energy and the reverse taking place in the pendulum would continue uninterruptedly (as in a mathematical pendulum). If it be conceived that the swinging pendulum-bob encounters exactly in the vertical plane a movable body resting at this point, such as a sphere, then (assuming perfect elasticity on the part of the pendulum-bob and the sphere) the kinetic energy of the pendulum-bob would be transmitted directly to the sphere: The pendulum would come to rest, while the sphere would continue in movement with equal kinetic energy (again providing there is no resistance). This is an instance of the transmission of kinetic energy from one body to another. Finally it may be conceived that a coiled clock-spring in unwinding causes another to become coiled. This would be an instance of the transmission of potential energy from one body to another. From the illustrations given the general proposition may be deduced : If in a system the individual moving masses approach a final condition of equilibrium, the sum of the kinetic energies in the system will be increased; and if the particles are removed from the final condition of equilibrium, then the sum of the potential energies is increased at the expense of the kinetic energies; that is, the kinetic energies diminish. 22 HEAT. The pendulum approaching the vertical plane (the position of equilibrium for a resting pendulum) from the highest point of its excursion possesses in this position the greatest amount of kinetic energy ; and ascending to the highest point of its excursion on the other side it attains, at the expense of the progressively diminishing movement and thereby also the kinetic energy, again gradually the maximum of potential energy. Heat : Its Relation to Kinetic Energy and to Potential Energy. If a leaden weight be thrown from the summit of a tower to the earth and there encounter an unyielding surface, its movement in mass will come to rest, but the kinetic energy, which to the eye appears dissipated, is transformed into an actively vibratory movement of the atoms. On striking the ground heat is generated, the amount of which is proportionate to the kinetic energy that is transformed by the impact. At the moment of contact on the part of the falling weight the atoms are set into vibration by the concussion. They impinge upon one another and then rebound in consequence of the potential energy that tends to prevent their immediate apposition; they separate to a maxi- mum degree in so far as the power of attraction of the ponderable atoms permits and they oscillate to and fro in this manner. All atoms oscillate like a pendulum until their movement is transmitted to all the surrounding ether- atoms, that is, until the heat of the heated mass is radiated. Heat is a vibratory movement of the atoms. As the amount of heat generated is proportionate to the kinetic energy that is transformed by the impact, it must be possible to find an adequate measure for both forms of force. The heat-unit (calory), that is, the energy that raises the tempera- ture of i gram of water i C., serves as the measure of the amount of heat. This heat-unit corresponds to 425.5 grammeters; that is, the same amount of energy that raises the temperature of i gram of water i C. is capable of raising a weight of 425.5 grams to a height of i meter; or, a weight of 425.5 grams falling from the height of i meter would in its impact generate so much heat as would raise the temperature of i gram of water i C. The mechanical equivalent of the heat-unit is therefore 425.5 grammeters. It is evident that from the impact of masses in motion an amount of heat of immeasurable degree may be generated. If this statement be applied to the planets, their impact would result in the production of an amount of heat greater than could be generated by any form of earthly combustion. If the earth were suddenly checked in its course and if through the force of gravitation it plunged into the sun [in the course of which it would eventually have acquired a terminal velocity of 630.7 kilometers in a second] an amount of heat would be generated in consequence of the collision equivalent to that produced by the combustion of more than 5000 equally heavy masses of pure carbon. In this manner the dem- onstration can be made scientifically, that even the sun's heat may have been produced by the impact of cold matter. If the cold matter of the universe were thrown into space, and there left to the attraction of its particles, the impact of these masses would eventually extinguish the light of the stars. In the same way numerous cosmic bodies still collide in space, and innumerable meteors constantly plunge into the sun (from 9400 to 188,000 billions of kilos in each minute). Thus, the action of the force of gravitation is in fact perhaps the exclusive origin of all heat. The following is an instance of the transformation of kinetic energy into heat: The smith makes a piece of iron hot by hammering. The fol- lowing is an instance of the transformation of heat into kinetic energy: The hot steam of the steam-engine causes the piston to rise. The following is an illustra- tion of the transformation of potential energy into heat : The unwinding of a coiled metallic spring, rubbing upon a rough surface, produces heat by friction. Exam- CHEMICAL AFFINITY OF ATOMS. 23 pies of like character, as well as of other transformations, could be readily given in any number. Chemical Affinity of Atoms : Relation to Heat. While the force of gravitation acts upon the particles of matter without reference to the character of the body, still another form of force is found in the realm of atoms, which is effective between the atoms of chemically different bodies, namely, chemical affinity. This is the force by means of which the atoms of chemically different bodies unite in chemical combination. The energy itself is extremely variable between the atoms of different chemical bodies. A distinction is made between strong chemical affinities (or rela- tions) and weak affinities. Just as it is possible to determine the kinetic energy of a body in motion from the amount of heat that it generates in its impact upon an unyielding surface, so the degree of chemical affinity can be determined from the amount of heat that is produced, as the atoms of chemically different bodies unite in chemical combina- tion; for if a complex body is formed from individual, chemically different atoms heat is, as a rule, generated. If as a result of the force of affinity the atoms of i kilo of hydrogen and 8 kilos of oxygen unite to form the chemical combination water, an amount of heat is generated that is equal to that developed by the impact of a weight of 47,000 kilos in falling from a height of 300 meters above the surface of the earth. One gram of hydrogen converted into water by addition of oxygen yields 34,460 heat-units (calories). One gram of carbon con- verted into carbon dioxid yields 8080 calories. Whenever in the course of chemical processes considerable affinities are satisfied heat is set free, that is, generated from the force of affinity. The force of affinity is a form of potential energy acting between the various atoms that in the course of the chemical process is transformed into heat. It is thus likewise explicable that in the course of those chemical processes through which strong affinities are dissolved, in which the chemically united atoms are again separated, cooling takes place, or, as is commonly stated, heat becomes latent. That is, the energy of the heat rendered latent is transformed into chemical poten- tial energy, and this in turn, after disintegration of the complex chemical body, appears between its isolated, individual atoms as chemical affinity. LAW OF THE CONSTANCY OF ENERGY. Julius Robert v. Mayer (1842) and Hermann Helmholtz (1847) have 'established the important law that in a system that receives no influ- ence or impression from without the sum of all the contained kinetic energies is always equal. The energies may be transformed one into another, so that the potential energy may be converted into kinetic energy, and the reverse, but never is even the slightest amount of the energy lost. The transformation that takes place in the energies occurs in a definite manner, so that from a definite measure of a given force an equally definite measure of the new-appearing force always results. . The forces occurring in the animal organism appear in the following modifications : i. As movement in mass (generally designated simply movement), 24 LAW OF THE CONSTANCY OF ENERGY. such as the movement of the entire body, of the extremities and many of the viscera; also appreciable even microscopically in cells. 2. As movement of the atom: in the form of heat. As is well known, the vibration of atoms results in the production of heat or of light or in chemically active waves in accordance with the number of vibrations in the unit of time. The smallest number of vibrations are those of heat, the highest those that are chemically active, and between the. two are the vibrations of light. In the human body only heat-waves have of these three been observed, but some lower forms of life are capable of causing also luminous phenomena. In the human organism movements in mass are constantly trans- formed in certain organs into heat, as, for instance, the kinetic energy in the circulatory organs, and which is transformed into heat by the resistance within the vascular apparatus. The measure of these trans- formations also is the unit of energy = i grammeter, and the unit of heat = 425.5 grammeters. 3. In the form of potential energy (latent energy) the organism con- tains many chemical combinations characterized especially by great complexity of constitution and imperfect saturation of the contained affinities, and, therefore, by their great tendency to break down into simpler bodies. The body is capable of generating both heat and kinetic energy from potential energies; kinetic energy, however, is always in combination with heat, while heat may be produced alone. The simplest measure of the potential energies is the amount of heat that can be obtained by the combustion of the chemical bodies in question representing the potential energy. As a secondary matter the number of equivalent units of energy can be determined in turn from the amount of heat generated. 4. It is known that the phenomena of electricity, magnetism and diamagnetism, may make themselves manifest in two directions, namely, in the form of movement of minutest particles, which may be recog- nized in the incandescence of a thin wire (the seat of great resistance) traversed by a strong current; and also in the form of movement in mass, as exhibited in the attraction or repulsion of the magnetic needle. In the body electric phenomena appear in the muscles, nerves, and glands ; but as compared with other forms of energy they are of subordinate importance. It is not improbable that the electric energy of the body is transformed almost wholly into heat. The endeavor to obtain a measure for electric energy, the unit of electricity, as a means of direct comparison with the heat-unit and the unit of energy, has likewise been attended with definite success. Luminous phenomena do not occur in the bodies of the most highly developed animals. The significant investigations of Hertz have shown that the phenomena of light exhibit the greatest analogy with those of electricity in the most important connections, so that the relations be- tween the two forms of energy must accordingly be admitted. It is certain that in the body also the different forms of energy can be transformed one into another in a definite and constantly invariable degree, and that new energy never develops spontaneously in the body, while that present is never destroyed ; and thus also the organisms are a theater in which the law of the constancy of 'energy is in unceasing operation. ANIMALS AND PLANTS. 25 The original statement of Julius Robert v. Mayer may be appropriately quoted at this point: "There is but one energy, which operates with unceasing change in dead and in living things, and nowhere in either does any change take place without alteration 'in the form of energy. Physics has but to investigate the metamorphoses of energy, as chemistry has to investigate the transformations of matter. The generation as well as the destruction of energy is beyond the range of human thought and action: Nothing comes from nothing, nothing can give rise to nothing. If chemistry teaches the immutability of matter, then it is the obliga- tion of physics to demonstrate the quantitative immutability of energy notwith- standing all variability in form. Gravitation, motion, heat, magnetism, electricity, chemical difference, are all but varying modes of manifestation of one and the same natural force that reigns throughout the universe, for any one can under special conditions be converted into another." (Lucretius Carus, born 95 B. C., had already said: "Nullam rem a nihilo gigni, .... neque ad nihilum interimat res.") ANIMALS AND PLANTS. Locked up in the constituent elements of the animal body is an aggregation of chemical potential energies (Lavoisier, 1789). The total amount of these in the human body could be measured if the entire cadaver were completely burned in a calorimeter and the number of heat-units generated were noted as a result of its combustion. The chemical combinations in which are bound up the potential energy are characterized by complexity in the arrangement of their atoms, by imperfect saturation of the affinities of the atoms, by a relatively small oxygen-content, and by a great tendency to and readiness of disintegra- tion. It may be conceived that food is withheld from an individual. The fasting person loses hourly 50 grams of body- weight; the tissues in which his potential energy is bound up are thus consumed. Through the taking up of oxygen combustion continually takes place, and as a result of this process the complex elements of the body are converted into simpler ones, whereby the potential energy forming the connecting link between them is transformed into kinetic energy. It is a matter of indifference whether the process of combustion takes place rapidly or slowly; the same amount of chemical matter always yields the same amount of kinetic energy, as, for instance, heat. After the lapse of a certain time the fasting person becomes conscious of the state of threatened exhaustion of his stored potential energy, and the condi- tion of hunger sets in. The hungry person takes food; all food for the animal kindgom is derived either directly or indirectly from the vege- table world. Even carnivorous animals, which eat the flesh of other animals, consume in the final analysis organized material formed from vegetable food. Thus, the existence of the animal kingdom necessarily implies unconditionally the previous existence of the vegetable king- dom. Vegetable structures thus contain all of the nutritive materials necessary for the animal body. In addition to water and inorganic matters, vegetables contain, among other organic combinations, espe- cially also the three principal representatives of nutrient bodies, namely, fats, carbohydrates, and proteids. All of these are the seat of abundant potential energy in accordance with the complexity of their chemical constitution. 26 ANIMALS AND PLANTS. Fats contain- { Cn H > (OH) == fatt ^ adds ^ 1 + C 3 H 5 (OH),= glycerin J ( C 7 6. 5 Animal fats contain : H 12.0 (. O 11.5 Carbohydrates contain: C 6 H 10 O 5 p ^50-55 H e .e- 7 .3 Proteids contain in percentages : N 15 _ 19 19 - 24 0.3-2.4 Man, who partakes of a certain amount of these nutrient materials, adds to them through the respiratory process the oxygen of the air, whence there results a process of combustion, in the course of which chemical potential energy is converted into heat. It is evident that the products of this combustion must be bodies of simple constitution, bodies with uniform arrangement of their atoms, with most complete saturation of the affinities of their atoms, of great constancy, partly rich in oxygen and possessing slight or no chemical potential energy. These bodies are carbon dioxid (CO 2 ), water (H 2 O), and, as the most important representative of the nitrogen-containing derivatives, urea (CO(NH 2 ) 2 ), which, while endowed with a small measure of potential energy is, outside of the body, readily transformed into CO 2 and ammonia (NH 8 ). Thus, the animal body is an organism in which, through the inter- mediation of oxidation-phenomena, the complex nutritive matters of the vegetable world, representing high potential energy, are trans- formed into simple chemical bodies, in the course of which the potential energy is transformed into an equivalent amount of kinetic energy (heat, work, electric phenomena). The question naturally arises, How do plants, which, as the first products of creation, found for their nourishment no preexisting mate- rials endowed with potential energy, and still suffer from no lack thereof how do plants form the complicated nutrient matters mentioned, rich in stored-up potential energy? This potential energy of vegetable life must obviously have been derived from some other form of energy, for it cannot be created out of nothing. This kinetic energy is furnished plants through the light of the sun, whose chemical rays they absorb. Without sunlight there can be no vegetable life. From the air and the earth the vegetable organism obtains CO 2 , H 2 O, NH 3 , and N, of which carbon dioxid, water, and ammonia (from urea) constitute also the excrementitious matters of the animal body. The plant obtains from the rays of the sun the kinetic energy of its light and converts it into potential energy, which, as in all vegetable matter, so also in the nutrient material produced, accumulates in the process of the growth of the plant. This formation of complex chemical combinations takes place in asso- ciation with elimination of oxygen. The Papillonacese, as, for instance, peas, beans, lupines, acacias, are capable of assimilating the free nitrogen of the air in the tissues of their root-bulbs, through the agency of symbiotic micro-organisms lodged upon these, Rhizobium legumino- sarum. Thus, these plants are capable of building up their nitrogen-containing tissues even in soil entirely free from nitrogen. In this way they play an im- portant fertilizing role in agriculture (lupine) and forestry (acacia). Also lower ANIMALS AND PLANTS. 27 forms of vegetable life, as, for instance, the anaerobic bacterium, Clostridium pasteurianum, is capable of assimilating free nitrogen. At times plants also exhibit free kinetic energy such as it is customary to encounter in the case of animals. Certain plants, as, for instance, the aroids and others, develop considerable amounts of heat during the flowering-period. It is also to be borne in mind that, in the development of the solid parts of plants, the transformation of formative fluids into solid matter causes heat to be set free. Absorption of oxygen and elimination of carbon dioxid have also been observed in plants. These processes are, however, so insignificant as compared with those described as typical in the vegetable kingdom, that they may be considered as of little or no importance. Thus, plants are, on the whole, organisms that through the agency of reduction-processes convert simple stable combinations into complex ones, with the transformation of kinetic solar energy into the chemical potential energy of vegetable matter. Animals are living organisms in which through the agency of processes of oxidation the atom-groups of complex construction furnished by plants are split up, the potential energy being transformed into kinetic energy, which makes itself mani- fest in the animal. Thus a circulation of materials and a constant interchange of energy take place between animals and vegetables. All of the energy of animals is derived from plants and all of the energy of plants is derived from the sun. Therefore, the latter is the cause, the ultimate source of all of the energy of organism, that is, of life as a whole. As the generation of the sun's heat and light can be explained by the gravitation of masses, so it is possible that the force of gravita- tion is the sole ultimate form of energy for all living things. "The sun is the constantly bent spring that brings about the activity in the atmosphere, that raises the waters to the clouds, that causes the tides. Light, the most mobile of all forms of force, intercepted by the earth in flight, is transformed by plants into a rigid state, for plants produce upon it a continuous sum of chem- ical difference, constitute a reservoir in which the fugitive rays of the sun are fixed and, adapted for useful purposes, are deposited. Plants take one form of energy, light, and reproduce another, chemical difference. In the course of the processes of life, but one transformation, both of matter, as well as of energy, takes place, but never is the one or the other produced " (Julius Robert v. Mayer, 1845). ("Omnia mutantur, nihil interit." Ovid.) The generation of kinetic energy in the animal body from the poten- tial energy of the plant can be ma'de readily comprehensible by means of a comparison. The atoms of the matter generated in organisms may be conceived to be simple small bodies, spherules or blocks. So long as these lie in a single layer or at least arranged in a few layers upon the ground, a condition of rest and constancy will prevail in consequence of this simple and stable arrangement. If, however, an artificially arranged formation of unstable construction is built up from the small bodies, there will be required (i) the motor force of the constructing agency, which raises and combines the units. As soon, however, as (2) an impulse from without acts upon the completed unstable structure, the atoms collapse and the impact of their fall generates heat (eventually also kinetic energy in the course of other complicated transformations), that is, the energy applied by the constructing agency is transformed into the form of energy last named. In plants the complicated unstable construction of the atom-groups takes place, the sun being the con- structing agency. In the animal body, wherein the plant is consumed, the atomic structure is disintegrated into simpler elements, with the generation of kinetic energy. 28 KINETIC ENERGY AND LIFE. KINETIC ENERGY AND LIFE. The forms of kinetic energy that are active in organisms, namely, plants and animals, are precisely the same as those that are recognizable in inanimate matter. A so-called ''vital energy," which is supposed to act as a special form of force of peculiar character and cause and control the vital phenomena of living organisms, does not exist. The forces of all matter, both organic and inorganic, are bound up in their smallest particles, the atoms. As, however, the smallest particles of organ- ized matter are generally united in a most complex manner, in con- trast to the ordinarily much simpler constitution of inorganic bodies, the forces inherent to the smallest particles of organism will appear in much more complicated phenomena and combinations, and as a result the explanation of the vital phenomena in the organism by the simple principles of physics and chemistry is rendered extremely difficult and in many respects appears impossible. Metabolism as an Index of Life. A special form of interchange in matter and energy appears peculiar to the living organisms of the earth. This consists in the ability to adapt themselves to the materials of their environment, and to assimilate them, so that for a time they represent integral parts of the living being, later again to be given off. The complete chain of these phenomena is designated "metabolism,' 1 which consists accordingly in ingestion, assimilation, reduction and excretion. It has already been suggested that metabolism differs in character in animals and in plants. As a matter of fact, this is, as has been shown, actually the case in animals and plants typically and characteristically developed. There is, however, a large group of organisms that in their complete organization exhibit such atypical development that they must be considered as undifferentiated fundamental forms of organisms. They cannot be recognized as either plants or animals, but represent the simplest form of animate matter. These organisms, as the earliest and most primitive forms, have been designated protists. It must be assumed absolutely that these also have a simple metabolism as a condi- tion of life, but with respect to this adequate observations are wanting. PHYSIOLOGY OF THE BLOOD. PHYSICAL PROPERTIES OF THE BLOOD. The color of the blood varies from bright scarlet-red in the arteries to the deepest dark bluish-red in the veins. Oxygen, therefore also the air, makes it bright red, while deficiency in oxygen renders it dark. The oxygen-free venous blood is dichroic, that is, it appears dark red in reflected light and green in transmitted light. In thin layers the blood is opaque, as one can readily convince himself, if blood be poured upon a glass plate and be permitted to flow off, by attempting to read printed matter through it. The blood thus behaves as a covering pigment, as its coloring matter is suspended in the plasma in the form of small granules, namely, the red blood-corpuscles. For this reason the granular coloring matter of the blood can be separated from the blood-plasma by nitration. This, however, is possible only after admix- ture of the blood with fluids that render the blood-corpuscles rough or viscid. If mammalian blood is mixed with one-seventh of its volume of concentrated sodium sulphate, or if frog's blood is mixed with two per cent, solution of cane sugar, and then filtered, the blood-corpuscles will remain upon the filter. The reaction of blood is alkaline from the presence of disodium phosphate (Na 2 HPO 4 ). The alkalinity rapidly diminishes in intensity after escape from the vessel, and the more rapidly the greater the pre- vious alkalinity. The change depends upon the development of an acid, in which the red blood-corpuscles take part in consequence of a decomposition of as yet undetermined origin. This generation of acid is increased by high temperature and the addition of alkali. The alkalinity of the blood is diminished (A) by active muscular exercise, in consequence of the development of acid in the muscular tissue. (B) By coagulation. Fresh clot has a more intensely alkaline reaction than blood-serum. (C) After the persistent use of soda the alkalinity of the blood is increased, and after the use of acid it is diminished. (D) Old blood or blood dissolved with water from dry- places generally has an acid reaction. The blood of children and women exhibits a lesser degree of alkalinity than that of men, and that of nursing women a lesser degree of alkalinity than that of pregnant women. The alkalinity is less also dur- ing digestion than during fasting. Method of Examinat^on. As in consequence of the normal color of the blood red litmus-paper cannot be employed directly in testing the reaction, the following plan is pursued: Blood is mixed with an equal volume of concentrated solution of sodium sulphate, and the mixture is placed upon highly porous and sensitive lilac- tinted litmus blotting-paper. The blood-corpuscles remain upon the surface while fluid is taken up by the paper and gives rise to the reaction. For the quantitative estimation of the alkalinity dilute tartaric acid is added to a volume of blood (7.5 grams of crystalline tartaric acid to i liter of water, i cu. cm. of which saturates 3.1 mg. of soda) until the blue paper is reddened. One hundred cu. cm. of human blood contains the alkaline equivalent of from 260 to 300 mg. of soda (in guinea-pigs 150 mg., in carnivora 180 mg. of soda). Landois' method for the quantitative determination of the alkalinity of the blood with only a few drops of blood : Tartaric acid in the concentration already stated is employed to neutralize the alkalinity of the blood. Of this the following mix- tures are made by addition of concentrated solution of neutral sodium sulphate: (i) 10 parts of tartaric-acid solution and 100 parts of concentrated sodium- 29 30 PATHOLOGICAL. sulphate solution; (2) 20 parts of tartaric-acid solution and 90 parts of sodium- sulphate solution; (3) 30 parts of tartaric-acid solution and 80 parts of sodium- sulphate solution; (4) 40 parts of tartaric-acid solution and 70 parts of sodium- sulphate solution; (5) 50 parts of tartaric-acid solution and 60 parts of sodium- sulphate solution; (6) 60 parts of tartaric-acid solution and 50 of sodium-sulphate solution; (7) 70 parts of tartaric-acid solution and 40 parts of sodium-sulphate solution; (8) 80 parts of tartaric-acid solution and 30 parts of sodium-sulphate solution; (9) 90 parts of tartaric-acid solution and 20 parts of sodium-sulphate solution; (10) 100 parts of tartaric-acid solution and 10 parts of sodium-sulphate solution. To each glass an excess of crystallized sodium sulphate is added to the point of insolubility. Of the blood to be examined i drop is mixed in a graduated tube prepared for the purpose with an equal-sized drop of the acid-sulphate mixture. Into a glass tube with a diameter of i mm. and drawn out at one extremity mercury is sucked to a height of about 8 mm. so that the tube is filled to the tip. The upper extremity of the thread of mercury is marked by the scratch of a file. The mer- cury is now drawn into the tube until its lower border reaches the file-mark. The upper border of the mercury is now marked with another file-scratch. In this way the small measuring apparatus is improvised. In order now to test the blood, one drop of the tartaric-acid sodium-sulphate mixture is sucked up to the lower mark, and then, after scrupulously drying the tip, the blood is drawn up until the fluid reaches the upper mark. After again cleansing the tip of the tube its contents are blown into a watch-glass, are well stirred and then tested with reagent-paper. Successively the mixtures 2, 3, 4, etc., are treated in the same way. The reagent-paper is cut into strips 3 mm. wide, and these are partially dipped in the blood-specimens in the respective watch-glasses. The blood-corpuscles collect about the immersed extremity of paper, while the fluid is sucked up beyond and indicates the reaction. If the test has been made successively in this manner with the mixtures from i to 10 it will be readily seen when the blue tint of the alkaline reaction ceases and the red tint of the acid reaction begins. In human beings the blood can always be obtained directly from a small needle-puncture. Exact suction into the tube can be effected with certainty and convenience if the upper extremity of the meastiring glass is connected by means of a short rubber tube with a hypodermic syringe, the movement of whose piston through a twisting motion facilitates an exact degree of suction. All of the tests must be completed with equal rapidity and at the same temperature. The degree of alkalinity in the adult will in general be satisfied by mixture 5 or 6, and in the child by mixture 4. If all parts of the blood are uniformly dis- solved previously by addition of water this solution, which obviously can no longer be designated blood, exhibits a somewhat higher degree of alkalinity. If blood is tested slowly by the method described the alkalinity will be that of such a solution. Pathological. Persistent vomiting and chlorosis are attended with increased alkalinity, while diabetes, as well as cachectic states, rheumatism, uremia, leuke- mia, profound anemia, high fever, cholera, carbon-monoxid poisoning, and degen- eration of the liver are attended with diminished alkalinity. Poisons that cause destruction of red blood-corpuscles likewise bring about reduction in the alkalinity. Blood has a peculiar odor. This "halitus sanguinis" differs in human beings and in animals, and depends upon the presence of volatile fatty acids. If sulphuric acid be added to blood, and these acids are in consequence set free from their combination with the alkali of the blood, the characteristic odor appears more distinctly. The blood possesses a salty taste, derived from the salts dissolved in the blood-plasma. The specific gravity of the blood is 1058 (from 1046 to 1067) in men, and from 1051 to 1055 i n women, while the blood of children has a lower specific gravity. The specific gravity of the red blood-corpuscles is 1105, that of the plasma from 1027 to 1028.3. This fact explains the tendency of the former to sink to the bottom. Method of Determination. For clinical investigation the following method (a modification of that described by Roy) can be recommended. In a glass tube, MICROSCOPIC EXAMINATION OF THE BLOOD. 31 narrow at the bottom and covered with a rubber cap, a fresh drop of blood ob- tained by puncture with a needle is permitted to enter from below. The tube is at once immersed in a glass vessel filled with a solution of olive-oil in chloroform, and by pressure upon the rubber cap the drop of blood is expelled into the fluid. Various concentrations of the latter with a specific gravity between 1050 and 1070 are prepared, and that solution in which the drop remains suspended indicates the specific gravity of the blood. The specific gravity is dependent principally upon the hemoglobin-content of the blood, much less upon the number of erythrocytes. It is high in the newborn, namely, 1066. The drinking of water and hunger will reduce the specific gravity temporarily, and it falls also after loss of blood and is lower in the presence of anemia, chlorosis, marasmus, and nephritis (down to 1025). It is increased by thirst, the digestion of solid food, by sweating, acute loss of water through the intestines and the kidneys, as well as cyanotic stasis (down to 1068). The entrance of an increased amount of salts into the blood is shortly followed by dilution, while the salts of the biliary acids, on the other hand, exert a concentrating influence. The specific gravity is increased by vasomotor contraction of the vessels and, con- versely, it is diminished by vascular dilatation. The blood-serum of women is heavier than that of men. If blood is made artificially to pass repeatedly through an organ its specific gravity increases in consequence of the taking up of dis- solved substances and the giving off of water. For the determination of the specific gravity of the red blood-corpuscles, these must be isolated by sedimentation. This takes place rapidly in the case of horses' blood. The erythrocytes are said to be somewhat heavier in women and to con- tain more hemoglobin than those of men. The freezing-point of the blood is about 0.56 C. It increases as the oxygen-content diminishes. MICROSCOPIC EXAMINATION OF THE BLOOD. The red blood-corpuscles or erythrocytes (Fig. i) were discovered in man by Leeuwenhoeck in 1673 and in the frog by Swammerdam in 1658. Physical Properties. Human erythrocytes are coin-shaped discs with biconcave surfaces and rounded margins. The diameter is 7.5 //, the thickness of the edge 2.5 /;., and the central thickness from 1.8 to 2 , (Fig. i). In health the diameter varies from 6 to 9 // ; the average being from 7.2 to 7.8 fi. The corpuscles are diminished in size by inanition, elevation of the bodily temperature, carbon dioxid and morphin, and increased in size by oxygen, a watery state of the blood, cold, ingestion of alcohol, quinin, hydrocyanic acid. [Pathological conditions are discussed on p. 50.] The volume of an erythrocyte equals 0.000000077217 cu. mm., the superficies 0.000128 sq. mm. If the total volume of the blood in man be assumed to be 4400 cu.cm., all of the contained blood-corpuscles have a superficies of 2816 square meters, that is, the equivalent of a square with, sides of 80 paces. In a second 176 cu.cm. of blood are driven into the lungs and whose blood-corpuscles exhibit a superficies of 81 square meters, that is, a square with sides 13 paces. The volume of all of the erythrocytes can be approximately determined by introduc- ing the blood into a narrow graduated glass tube ("hemokrit" of Hedin), either unmixed or defibrinated or mixed with an equal amount of a preservative fluid capable of preventing coagulation, as, for instance, 2.5 percent, potassium-bichrom- ate solution or 0.86 percent, sodium-chlorid solution with some ammonium oxalate, and subjecting 'it to centrifugation. Treated in this manner healthy human blood is found to contain from 42 to 48 per cent, of corpuscles (anemic blood 30 per cent, and less). The erythrocytes, however, undergo changes in vol- ume, at least after escape of the blood, by the taking up or giving off of fluid material, as exhibited beyond doubt by shrunken and distended forms. Venous blood contains a greater volume of erythrocytes than arterial blood. The iveight of an erythrocyte can be determined by multiplying its volume by its specific gravity (1105) = 0.000000085325 mg. 32 MICROSCOPIC EXAMINATION OF THE BLOOD. Alexander Schmidt determined the weight of the red blood-corpuscles in 100 parts of blood in the following manner: He ascertained (i) the percentage of dry residue of the blood = T; (2) the percentage of dry residue of the corresponding blood-serum = t; (3) the dry residue of the erythrocytes contained in 100 grams of blood = r; the dry residue of the serum obtained from 100 grams of blood is then T r, the corresponding amount of serum - ; further, the weight of the erythrocytes in 100 parts of blood = 100 - ; the latter equals 48 grams in 100 grams of blood from a man and 35 grams in the same amount of blood from a woman. Number. In men the number of red blood-corpuscles is more than 5,000,000, while in women it is about 4,000,000 in i cubic millimeter, making 25 billions in 5 kilos of blood. The number is in inverse pro- portion to the amount of the plasma, and from this fact it will be seen FIG. i. A, human colored blood-corpuscles: i, on the flat; 2, on edge; 3, rouleau of colored corpuscles. B, amphibian colored blood-corpuscles: i, on the flat; 2, on, edge. C, ideal transverse section of a human colored blood-corpuscle magnified 5000 times linear: ab, diameter; cd, thickness. that the number must vary in accordance with the state of contrac- tion of the vessels, conditions of pressure and diffusion - currents and the like. The number of red blood-corpuscles is increased in venous blood (at times in small cutaneous veins and in the presence of stasis) , after the ingestion of solid food, after rest at night, after marked loss of water through the skin, the intestine or the kidneys, during inanition (in consequence of the consumption of blood- plasma), in the blood of the newborn, at times after late ligation of the umbilical cord (from the fourth day the number again becomes reduced) , in persons of vigorous constitution and in residents of the country. The number is dimin- ished during pregnancy and after copious libations. The capillaries contain relatively few blood-corpuscles. Apparent increase or diminution must also ac- company variations in the amount of plasma, and to this fact special attention should be given in investigating the effect of certain influences upon the number of erythrocytes. Thus, for instance, the increased number observed in those re- siding at a high altitude may depend, wholly or in part, upon a greater or lesser reduction in the plasma. In the earlier stages of fetal life the number is from J to i million in i cu. mm. Method of Counting Blood-corpuscles. An exact mixing apparatus for the dilution of the blood is the first requirement. For this purpose the mixer of Potain will answer (Fig. 3). This is a carefully calibrated, pipet-like glass instru- METHOD OF COUNTING BLOOD-CORPUSCLES. 33 merit, whose tip is dipped into the blood, which by suction through a rubber tube is drawn into the pipet either to the mark \ or to the mark i. The tip carefully dried is then immersed in 3 per cent, sodium-chlorid solution, which is sucked up until it reaches the mark 101. By shaking the mixer a spherule (a) in the bulbous enlargement of the apparatus is moved about so as to effect a homogeneous mix- ture. If the blood be sucked up to the mark \ the mixture will be as i to 200, and if up to the mark i as i to 100. For the enumeration of the cells a small amount of the blood-mixture is intro- duced into the Abbe-Zeiss counting-chamber (Fig. 2) , the first few drops being thrown away. Upon a slide is cemented a glass cell, o.i mm. deep, upon whose floor are etched a series of squares and which is surrounded by a groove or depres- sion and is provided with a cover-glass to be placed over it. The space overlying each square has a capacity of ?7T Vo cu. mm. The number of cells in each square is estimated and this multiplied by 4000 gives the number of corpuscles in each FIG. 2. Apparatus of Abbe and Zeiss for Counting the Cor- puscles: A, in section; C, surface view without cover- glass; B, microscopic appearance with the blood-cor- puscles. FIG. 3. The Melangtur, pipet or mixer. cu. mm. The result thus obtained must be multiplied by 100 or 200, according as the blood has been diluted 100 or 200 times. To ensure greater accuracy the contents of a large number of squares should be counted and the average take Vierordt, Malassez, Gowers, and others have devised similar forms of apparatu for the same purpose. To count the white blood-corpuscles alone in the chamber the blood i with 10 parts of a per cent, solution of acetic acid, which dissolves out the red corpuscles. It is advisable to stain the leukocytes in the blood-mixer, and can be done with some such solution as the following: 50 cu. cm of a I per c of solution of sodium chlorid with 5 drops of a 5 per cent, alcoholic s gentian-violet or hexamethyl-violet. 3 34 THE RED BLOOD-CORPUSCLES. The red blood-corpuscles are characterized by their great elasticity, flexibility, and softness. THE RED BLOOD-CORPUSCLES (ERYTHROCYTES). Individually the red corpuscles are of a yellowish color with a greenish tint. They are unprovided with either capsule or nucleus, but consist throughout of a homogeneous mass. This consists (i) of a framework of exceedingly pale, soft protoplasm, the stroma or cytoplasm, and (2) of the red blood coloring-matter, the hemoglobin, which impregnates the stroma (like paraplasm), in the same way as a sponge takes up fluid. INFLUENCES AFFECTING THE VITAL PHENOMENA OF RED BLOOD- CORPUSCLES. Blood-corpuscles retain in unimpaired degree their vital and func- tional activities in shed blood and even in defibrinated blood subse- quently returned to the circulation. Heat has an influence upon their vitality. If blood be heated to a temperature in the neighbor- hood of 52 C. the vital activity of the erythrocytes is destroyed. This fact is evident from the circumstance that the corpuscles in such blood are soon dissolved when returned to the circulation. Kept in FIG. 4. Red Blood-corpuscles: a, b, normal human red corpuscles, the central depression more or less in focus; c, d, e, mulberry, and g, h, crenated forms; k, pale corpuscles decolorized by water; 1, stroma; f, frog's blood- corpuscle acted on by a strong saline solution. the cold in a flask exposed to the influence of ice-water mammalian blood may retain its functional activity for 4 or 5 days. Removed from the body for a longer period of time and then returned to the cir- culation the red corpuscles rapidly undergo destruction an evidence that they have lost their vital activities within this time. The erythrocytes in blood recently removed from a vessel frequently exhibit changes in form that result in their assuming a mulberry-like appearance. These have been attributed to active contraction on the part of the stroma. Nevertheless, it must as yet be considered doubtful whether this is to be looked upon as an obvious vital phenomenon. It is true, however, that Max Schultze has observed active contractility and motility in the red blood-corpuscles of quite young embryo chickens. In support of the vital activity of the red corpuscles the fact may be cited that certain substances dissolved in the plasma are INFLUENCES AFFECTING PHYSICAL RED BLOOD-CORPUSCLES. 35 not capable of diffusing into the red blood-corpuscles, as, for instance, solutions of potassium, of iron, and of manganese, although other sub- stances do enter, as, for instance, sugar and chloroform. Nucleated erythrocytes are undoubtedly cells, while the non-nucleated ery- throcytes cannot properly be so considered. The latter have, therefore, been designated blood-plastids. INFLUENCES AFFECTING THE PHYSICAL PHENOMENA OF RED BLOOD- CORPUSCLES. The color of the red corpuscles is changed characteristically by a number of gases. Thus, oxygen, therefore also the air, renders the blood scarlet red, deficiency of oxygen renders it dark bluish red, carbon monoxid renders it cherry red, nitrogen monoxid renders it violet red. All agents that cause marked contraction of the erythrocytes induce a bright scarlet-red color; as, for instance, concentrated solution of sodium sulphate, from the action of which the corpuscles become mulberry- shaped or distorted into the shape of a key, and in a measure attenu- ated. The color thus produced is brighter than is ever observed in the arteries. Those agents that make the corpuscles globular, as particu- larly water, cause the color of the blood to become darker. If a dry preparation of blood be treated with concentrated solution of methyl- ene-blue diluted half with water some of the erythrocytes, particularly degenerated ones, become stained. It is the larger ones that are especially numerous in the presence of anemia and leukemia. Change in Position and Form. A phenomenon frequently observed in recently shed blood is the arrangement of the corpuscles like rolls of coin (Fig. i, A, 3). The conditions that increase the coagulability of the blood favor this phenome- non, which is to be attributed, in addition to the attraction of the discs, to the formation of a viscid substance. The condition is favored by warming moderately the slide upon which the fresh drop of blood is received. If under such circum- stances agents are added to the blood capable of causing the corpuscles to swell, the rolls separate as the individual corpuscles are transformed into globules. The adhesive substance uniting the erythrocytes, and which not rarely is drawn out into filamentous threads, is derived from the peripheral layer of the corpuscles. It consists of the stroma-fibrih, formed on the surface of the corpuscles in conse- quence of the inception of an injury at the periphery, and which has become viscid. The changes in shape that the erythrocytes may gradually undergo after leaving the body, up to the point of dissolution, are of especial interest. Some agents bring this series of changes about in rapid suc- cession. If, for instance, blood is exposed to the action of the spark of a Leyden jar, all of the corpuscles become at first mulberry-shaped, that is, the surface becomes rough and soon covered with at times small, at other times large, round nodules (Fig. 4, c d e). If the action be more pronounced the blood-corpuscles become almost globular, with many projecting points, thorn-apple-like (gh); this is probably an indication of the death of the corpuscle. At a further stage the action causes the corpuscles to assume a perfectly globular shape (ii). In this form they appear smaller than normal, as their disc-shaped mass is contracted into a sphere with a lesser diameter. The globules thus formed are viscid, and adjacent corpuscles readily adhere to one another 'and like fat-globules they may unite to form larger spheres. If the 36 PRESERVATION OF RED BLOOD-CORPUSCLES. action be continued for a still longer time, the blood coloring matter eventually separates from the stroma (k), and the blood-plasma con- sequently becomes reddened, while the stroma is recognizable only as a faint shadow (i). The changes in shape described represent the effects also of a number of other injurious agents causing dissolution of the red blood-corpuscles. Thus, for instance, all of the changes in shape can be observed also in putrid fluid. Influence of Heat. If a blood-preparation be heated upon a warm stage the corpuscles will be seen to undergo remarkable changes in shape when the temperature reaches 52 C. They become in part globular, in part drawn out into the shape of a biscuit, at times per- forated, or larger or smaller drops of the substance of the body are com- pletely constricted off. and float about in the surrounding fluid. This is an evidence that considerable degrees of heat destroy the histological individuality of the corpuscles. If the temperature be high and its influence long continued, the erythrocytes are finally entirely dissolved. In the case of burns the blood-corpuscles may undergo the same changes within the vessels. The addition to blood of a concentrated solution of urea acts in the same way as heat. Blood-corpuscles can be broken into fragments in microscopic preparations by strong pressure. The disintegration of blood-corpuscles into frag- ments may be designated erythrocytotrypsy, in contradistinction from their dis- solution, which is known as erythrocytolysis. If a finger moistened with blood be passed over a hot glass plate so that the thin layer of fluid is rapidly dried, the most remarkable forms of long drawn-out distorted blood-corpuscles can be seen. This ex- periment demonstrates in a striking manner their marked softness and elasticity. If blood be mixed with a concentrated solution of mucilage and if, while being examined under the microscope, concentrated solution of sodium chlorid is added, the corpuscles become drawn out into longitudinal masses (dragon-shaped) . The same change is observed if blood be admixed with an equal amount of liquid gela- tin at a temperature of 36 C., and sections are made after the gelatinous mass has hardened. PRESERVATION OF RED BLOOD-CORPUSCLES. The following are admirable preservative fluids for red blood-cor- puscles : Pacini's Mixture. Hayem's Fluid. Mercuric chlorid, 2. Mercuric chlorid, 0.5. Sodium chlorid, 4. Sodium sulphate, 5. Glycerin, 26. Sodium chlorid, i. Distilled water, 226. Distilled water, 200. To be diluted with two parts of dis- tilled water before being used. In order to avoid all influence of the air in the examination of fresh blood the following procedure is recommended: A drop of Pacini's fluid is placed upon a portion of the skin, which is then punctured with a fine needle through the fluid. In this way the blood rises into the preserva- tive fluid without having at any time come in contact with the air and the form of the corpuscles is at once fixed. In examining blood for medico-legal purposes the microscope is naturally always employed. Dried spots are carefully softened by PERMEABILITY OF ERYTHROCYTES. 37 means of concentrated or 30 per cent, solution of potassic hydrate, or with some preservative fluid, without friction. By softening them with the aid of concentrated tartaric-acid solution the leukocytes appear with especial distinctness. Often, however, search for the presence of blood-corpuscles will be fruitless. Red, suspicious fluids are examined directly. If the blood-corpuscles in the fluid have possibly already become pale, or if they are present only as stroma, the addition of a wine-yellow aqueous solution of iodin-potassium-iodid to the micro- scopic preparation will at times render them much more distinct. Saturated solution of picric acid, 20 per cent, solution of pyrogallic acid and 30 per cent, solution of silver nitrate have also been recom- mended for this purpose. PERMEABILITY OF ERYTHROCYTES. ISOTONIA (HYPERISO- TONIA AND HYPISOTONIA). DEMONSTRATION OF THE STROMA-LAKE COLORATION OF THE BLOOD. All substances soluble in water attract water with a certain intensity. The energy by means of which this attraction takes place is known as hygroscopic energy or osmotic tension. The manner in which this behaves with regard to living cells was discovered by de Vries (1884). A vegetable cell consists of a membrane, which is permeable to salts and to water. This membrane is in contact by its inner surface with the adjacent cell-protoplasm, which likewise is permeable to water, but not to salts. If fresh vegetable cells are placed in distilled water, this passes through the cell-membrane and through the cell-protoplasm, and causes the cells to swell. If, however, the cells are placed in a strong saline solution, the cell-contents shrink, because water is abstracted from them. The shrinking of the cellular protoplasm is shown by the fact that the protoplasm contracts upon all sides and becomes detached from the cell-membrane. This detachment of the shrunken cell-body from the cell-wall in consequence of loss of water is designated plasmolysis by de Vries. Plasmolysis is the more pronounced the more concentrated the saline solution surrounding the vegetable cell. The saline concentra- tion that brings about the first signs of plasmolysis can be determined experimentally for every variety of cell. The different salts must be employed in various concentrations, in order to bring about the same degree of plasmolysis. Solutions of different salts that exert the same effects in the process of plasmolysis are designated isotonic solutions. The necessary concentrations are to each other as the molecular weights of the different salts. For instance, a 0.58 per cent, solution of sodium chlorid causes the beginning of plasmolysis in the same way as a i.oi per cent, solution of potassium nitrate, or as a 1.5 per cent, solution of sodium iodid. The molecular weights of the three substances are 58, 10 1 , and 150 respectively. Isotonic solutions have the same freezing- point, which always becomes lower with increasing concentration; and also the same boiling-point, which becomes higher with the degree of concentration. There is thus for the red blood-corpuscles a given concentration for certain but not all substances in which they neither shrink nor swell. For mammalian erythrocytes this is a 0.9 per cent, solution of sodium chlorid for the frog 0.6 per cent. If the equally effective degree of 38 PERMEABILITY OF ERYTHROCYTES. centration is determined for other salts, the isotonic solutions will be established. Obviously the blood-plasma likewise is such an isotonic solution, as the erythrocytes retain their form perfectly within it. Those solutions are hyper isotonic, that is, of greater concentration, that abstract water from the erythrocytes and therefore cause them to shrink; while those solutions are designated hypisotonic, that is, of feebler concentration, that yield up water to the erythrocytes and there- fore cause them to swell. Although the erythrocytes preserve their form in isotonic solutions, nevertheless an interchange may take place between the soluble sub- stances in their interior and those of the surrounding fluid. Thus, chlorids, phosphates, and proteids, for instance, pass from one to the other. Under such circumstances, however, the isotonia is preserved. If, therefore, substances pass from the erythrocytes into the surrounding blood-plasma, other substances must, conversely, pass into them in order to preserve the isotonia. The red corpuscles thus possess the property of maintaining a constant degree of osmotic tension with refer- ence to certain substances. If, for instance, small amounts of an acid, and also carbon dioxid, be added to blood, albumin and phosphates pass from the corpuscles into the plasma, while, conversely, chlorids pass from the latter into the erythrocytes to maintain the isotonia. In consequence, the corpuscles become somewhat globular and their diam- eter diminishes in size. The blood-corpuscles exhibit the reverse inter- change and effect in shape after addition of small amounts of alkali. Van 't Hoff discovered in 1887 the law that the interchange of sub- stances in solution takes place according to the same laws as those applicable to gases, namely, the osmotic pressure corresponds entirely to the tension of a gas. The laws of gases laid down by Boyle- Mariotte are, therefore, applicable also to substances in solution. Ac- cordingly, and by reason of the diversity of the soluble substances con- tained within the cells and in the surrounding fluids currents must arise between the two in consequence of the osmotic pressure. If, therefore, erythrocytes, which behave like sacs filled with saline solutions, are placed in another saline solution, phenomena appear entirely analogous to those that occur when a sac filled with gas is introduced into another gas. The erythrocytes floating in a solution retain their volume only if the fluid is isotonic; that is, if it exerts the same osmotic pressure and if the substances dissolved in the surrounding solution cannot enter the corpuscles. If the osmotic pressure in the surrounding fluid is dimin- ished the corpuscle swells until it becomes completely dissolved in water, whose osmotic pressure is zero. The blood then becomes lake- colored. Exactly the same effect as is produced by distilled water must be produced also by the solution of a substance, quite independ- ently of the degree of its osmotic pressure, if the substance in solution readily penetrates the blood-corpuscles, and therefore can exert no pressure upon its wall. Under such circumstances also the corpuscle will undergo dissolution and the blood become lake-colored. The phenomenon of the blood becoming lake-colored, which is easily recognizable, indicates, therefore, that the blood-corpuscles are either in a solution of low osmotic pressure or in a solution whose osmotic pressure is not manifest because the wall of the corpuscles is impervious PERMEABILITY OF ERYTHROCYTES. 39 to the substance in solution. Among those solutions in which the blood- corpuscles are dissolved, independently of the degree of osmotic pres- sure of the solution, urea occupies the first place. The ammonium salts, with the exception of the sulphate, behave in the same manner. Certain exceptions to which the laws of osmotic pressure for the blood- corpuscles do not appear to apply H. Koeppe has been able to explain according to the theory of solutions of van 't Hoff. The circumstance must be taken into consideration, as Ostwald was the first to point out, whether, in accordance with the concentration of their solution, the dissolved substance has or has not completely dissociated itself into its ions. Many agents separate the coloring-matter from the stroma. In consequence the hemoglobin is dissolved in the blood-plasma, and the blood becomes transparent, as it contains the coloring-matter in the form of a transparent pigment. It is, therefore, designated lake- colored. Lake-colored blood is dark red. In the dissolution of the erythrocytes the change does not affect the aggregate condition, but it consists only in a transposition of the hemoglobin, which leaves the stroma and passes over into the blood-plasma. Therefore, no reduction in temperature takes place. Method. For the microscopic demonstration of the stroma it is recommended that a one per cent, solution of tartaric acid blood mixed with an equal volume of concentrated sodium sulphate be carefully added. In order to obtain an abundance of stroma for chemical examination, denbrinated blood is mixed with 10 volumes of a solution of sodium chlorid containing i volume of the concentrated solution and from 1 5 to 20 volumes of water. In this the stromata are precipitated as a whitish sediment. The following agents effect separation of stroma and hemoglobin: (a) Physical agents: (i) Heating of the blood to a temperature of 60 C. The degree of heat differs, however, in different animals. (2) Repeated freez- ing and thawing. (3) The static spark, although not after salts have been added to the blood, and the constant and induced currents. (b) Chemically active substances generated within the body: (4) Bile or bile-salts. (5) Serum from other species of animals. Thus, for instance, the serum of dogs' blood and of frogs' blood dissolves the blood-corpuscles of the rabbit in a few minutes. According to Rummo, Maragliano, and Castellino the blood-serum in cases of acute infectious disease and chronic dyscrasias is said to be destructive to the erythrocytes of healthy individuals. (6) Lake-colored blood from a number of other species of animals. (c) Other chemical reagents: (7) Water. (8) Exposure to the vapors of chloroform, ether, amylene; small amounts of alcohol, paraldehyd, thymol, nitrobenzol, ethylic ether, acetone, petroleum ether, and others. (9) Antimony hydrid, hydrogen arsenid, carbon disulphid. (10) Solutions of certain salts may be mixed with blood in a definite concentration without causing change in the red blood-corpuscles. If the saline solution is made either more dilute or more concentrated, dissolution of the corpuscles takes place. This is the case, for instance, with sodium chlorid. Traces of alkali render the erythrocytes more resistant to such solutions, while traces of acid exert an injurious effect.' Accord- ing to Bernstein and Becker salts cause an increase in the resistance to physical solvents, but a reduction to chemical solvents. (n) Addition of boric acid, i per cent., to amphibian blood causes the red mass, which at the same time sur- rounds the nucleus when present and is designated zooid, to escape from the stroma, which is designated ecoid, to withdraw from the periphery to the inte- rior of the corpuscles, and often entirely to pass out. Briicker, therefore, consid- ers the stroma to a certain degree a repository within which is lodged the remain- ing substance of the blood-corpuscles especially endowed with vital phenomena. (12) Strong acid solutions dissolve the blood-corpuscles, while weaker solutions cause precipitates in the hemoglobin. This can be distinctly observed in the case of carbolic acid. (13) Alkalies in moderate concentration cause sudden dis- solution. Addition of potassic-hydrate solution of about 10 percent, to the blood 40 FORM, SIZE, AND NUMBER OF ERYTHROCYTES IN ANIMALS. from the margin of a cover-glass permits the process of dissolution to be readily observed microscopically. At first the corpuscles abruptly become globular in jerks and thus apparently smaller; later they swell up like soap-bubbles. The influence of the gaseous content of the red blood-corpuscles upon their solubility is remarkable. The corpuscles in blood containing much carbon dioxid are dissolved most readily; those in blood containing much oxygen are much less readily dissolved; while between the two are the corpuscles containing much carbon monoxid. Total removal of the gases of the blood causes of itself the devel- opment of a lake-color. The erythrocytes possess a certain degree of resistance to the action of solvents. The following method may be employed to determine this degree readily. A drop of blood is mixed with an equal amount of a 3 per cent, solution of sodium chlorid, and then as much distilled water is added as is required to dissolve all of the red blood-corpuscles. The method is carried out as follows with human blood: With the aid of the blood-mixer of the blood-corpuscle counting-apparatus (Fig. 3) blood is collected from a puncture of the skin up to the mark i, and is expelled for microscopic examination into a concave glass cell, in which previously an equal amount of a 3 per cent, solution of sodium chlorid had been placed. Well admixed, all of the erythrocytes will be preserved. Now, by means of the same apparatus, distilled water is added, and the changes observed under the microscope until all of the red corpuscles are dissolved. The glass cell is covered after each addition in order to prevent evaporation. The erythrocytes of some persons are more readily dissolved than is normal, being soft and plastic and under- going striking changes. In addition, reference may be made to the following states: All blood-mixtures that jeopardize the normal condition of the erythro- cytes, such as cholemia, intoxications with substances that cause dissolution of the blood-corpuscles and high grades of venosity. Interesting observations may be made further in the presence of blood-diatheses and infectious processes, hemo- globinuria, and burns. The resistance appears diminished in case of anemia and of fever. FORM, SIZE, AND NUMBER OF ERYTHROCYTES IN DIFFERENT ANIMALS. All mammals, with the exception of the camel, the llama, the alpaca, and related animals, as well as the cyclostomata among fish, for instance the lamprey, have coin-shaped circular erythrocytes. The mammalia excepted have oval erythrocytes without nuclei, while birds, reptiles, amphibia (i, B) and fish, with the exception of the cyclostomata, have similarly shaped erythrocytes with nuclei. Size M = o.ooi Millimeter. Coin-shaped Oval Blood-corpuscles. Blood-corpuscles. Short Diameter. Long Diameter. Elephant, 9.4 // Llama, 4.2 // 7.5 /u Man, 7.5 Dog, 7.2 Rabbit, 7.16 Cat, 6.2 Sheep , 5.0 Goat, 4-25 Musk-deer, 2.5 Pigeon, 6.5 " 14.7 Frog, 16.3 " 23.0 ' Triton, 19.5 " 29.3 ' Proteus, 35.6 " 58.2 ' The corpuscles of the amphiuma are about a third larger than those of proteus. Among vertebrates, the blood of the amphioxus is colorless. The large blood- corpuscles of many amphibia can be seen with the naked eye. In those of the frog a nucleolus is demonstrable. It is readily explicable that the larger the blood-corpuscles the smaller must be their number and their total superficies in a given volume of blood. Only in birds is the number relatively larger than in other classes of vertebrates, notwithstanding the greater size of the corpuscles. This probably depends upon the fact that in them metabolism exhibits the greatest energy. Among mammals carnivcra have a larger number of blood- DEVELOPMENT OF RED BLOOD-CORPUSCLES. 41 corpuscles than herbivora. In goats the blood contains 19,000,000 blood-corpus- cles in the cubic millimeter; in the llama, 13,186,000; in the bull finch, 3,600,000; in the lizard, 1,292,000; in the frog, 408,900; in the proteus, 33,600. During the sleep of winter Vierordt observed the number of blood-corpuscles in the mar- mot diminish from 7,000,000 to 2,000,000 in a cu. mm. In invertebrates the blood is generally colorless, with colorless cells. In some invertebrates, for instance the earth-worm, the larva of the large gnat, and others, the plasma is red and contains hemoglobin, but the blood-corpuscles are colorless. Red, violet, brownish, greenish, opalescent blood, with colorless corpuscles (ame- boid cells), is found in some mussels. In the cephalopods and in certain snails and crabs a bluish, globulin-like coloring-matter is present in the blood, containing copper and combining with oxygen, hemocyanin, which is decolorized by a defi- ciency of oxygen. Certain round-worms have a green respiratory pigment, chloro- cruorin, while other animals have a yellow, red, or brown pigment of similar function . DEVELOPMENT OF RED BLOOD-CORPUSCLES. A. The embryonal development of the blood-corpuscles begins in the chicken as early as the first day. The corpuscles develop in groups within large globules of protoplasm that detach themselves from the walls of the vascular spaces resulting from the apposition of the forma- tive cells. At first they are globular, rough, nucleated, larger than the permanent cells and unpigmented. At a later period they take up the coloring-matter and attain their definite form, with reten- tion of the nucleus. Only when the vessels enter into communication with the heart, are the corpuscles swept away or isolated in groups, and then become set free in the circulation. Remak demonstrated all stages of their multiplication by division. Cells dividing by mitosis are observed most abundantly between the third and the fifth day of incubation, but no longer after their escape. Multiplication takes place by division also in the larvae of amphibia, as well as during fetal life in mammals in the spleen, the bone-marrow and the liver, and in the circulating blood. Neumann, further, found in the liver of the embryo, protoplasmic cells descendants of the vas- cular endothelium or of the liver-cells enclosing red blood-corpuscles. Besides, there were found in the liver cells with large nuclei, in part con- taining hemoglobin, in part free from hemoglobin, which divided by mitosis and then, with shrinking of the nucleus, became transformed into definitive blood-corpuscles. Foa and Salvioli observed endogenous formation in the lymphatic glands, in addition to the liver and spleen, also within large protoplasmic cells. The spleen also is considered a seat for the formation of the red blood-corpuscles, though only during embryonal life. Here the red corpuscles are believed to be formed of yellow, round, nucleated cells, representing transitional forms. From the embryonal bodies (erythroblasts), always at first nucleated, there result, in the later stages of embryonal life, the characteristically shaped and at the same time non-nucleated corpuscles; the nucleus, together with a portion of the protoplasm, disappearing. In the human embryo only nucleated corpuscles are present in the fourth week. In the third month they constitute only from one-eighth to one-quarter of all the erythrocytes, while at the end of fetal life nucleated corpuscles are found only with great rarity (Fig. 8). According to some observers, mammalian erythrocytes contain a nucleus-like central body, which Lavdowsky considers as the remains of nuclear substance. According to J. Arnold, the central body sometimes observed consists of a gran- 42 DEVELOPMENT OF RED BLOOD-CORPUSCLES. ular-filamentous transformation of the previous nucleus. This body, designated nucleoid, is surrounded by a zone of paraplasm, enclosing hemoglobin and gran- ular and hyaline matter "in a filamentous framework. Nucleoid and paraplasm may under certain conditions be extruded from the erythrocytes. Perhaps these contribute to the formation of blood-plates. B. Development of Vessels and Blood-corpuscles in the Earliest Pest- embryonal Period. Following J. Arnold, Golubew believes that the blood - capillaries present in the tail of frog -larvae form in various situations at first solid buds that grow more and more deeply into the tissues, enter into anastomotic union with adjacent buds and finally become hollow, with disappearance of their protoplasmic contents. The capillaries would thus like an intricate branched network make their way into the tissues and spread like a foreign intruder. Ranvier observed the same process of growth in the omen turn of newborn cats. The development of the capillaries and at the same time of the blood- corpuscles in their interior has been observed in an especially instruc- tive manner in the large omentum of the young rabbit. .When a week old, the omentum in these animals exhibits dull- white spots in whose in- terior lie so-called vessel- forming or vaso-formative cells (Fig. 5), that is, strongly refracting cellular elements varying widely in shape, and provided with protoplasmic processes (a). The protoplasm of these cells resembles that of the lymph-cells, particularly with respect to its mark- FlG. 5. Formation of Red Blood-corpuscles within "Vaso-forma- ^^1 1 Tr rp.ft-a r>-rin cr r>li a t-a r>t Ar five Cells," from the Omentum of a Rabbit Seven Days Old: r, r, the formed corpuscles; K, K, nuclei of the yaso-forma- in the interior OI these capuiariis."' a> pr cesses which ultimatdy unite to form cellular structures can be seen rod-shaped nuclei ar- ranged longitudinally (K K) and red blood-corpuscles (r r), both sur- rounded by protoplasm. From the vessel-forming cells protoplasmic shoots and processes arise, which in part terminate free and in part unite to form a delicate network. In some places nucleated connec- tive-tissue corpuscles arranged longitudinally lie upon the structures. These constitute the beginning of the connective-tissue perivascular sheath. The vessel - forming cells appear in various shapes, either longi- tudinally cylindrical, with pointed extremities, or round or oval, rather resembling large lymph -cells or connective-tissue cells. These cells are always the seat of origin of non-nucleated erythrocytes, which thus arise in the protoplasm of the vessel-forming cells, as the chlorophyl- grains or starch-granules arise in the protoplasm of vegetable cells. Only after the blood-corpuscles have thus formed within their interior do these cells unite through their processes with the vascular system. Their tubular arrangement becomes connected with adjacent vessels and the blood-corpuscles are washed away. In rabbits from four to six weeks old these areas contain fewer and fewer corpuscles. If it be DESTRUCTION OF RED BLOOD-CORPUSCLES. 43 borne in mind that Schafer observed similar formative processes in the subcutaneous connective tissue of young rats, the question must arise whether such blood-forming stations do not exist in many parts of the body and constitute seats for the regeneration of the blood. For purposes of demonstration it is only necessary to observe omentum of suitable age in a fresh state in peritoneal fluid, evaporation being prevented by applying paraffin to the edges of the cover-glass. Landois saw preparations of this highly interesting developmental process in the laboratory of Ranvier at Paris with such a degree of distinctness as to leave in his mind no doubt as to the accuracy of the observation. Neumann saw analogous formations in the embryonal liver, Wissotzky in the amnion of the rabbit, Nicolaides in the mesen- tery of the guinea-pig, Klein in the amniotic sac of the chicken's egg, Bayerl in the cartilaginous capsules of ossifying cartilage, Leboucq and Hayem in other situations, all indicative of the fact that the blood-cells develop endogenously in certain cellular structures of considerable size whose protoplasm serves at the same time for the formation of the vessel-wall. C. At a later period of life the red blood-corpuscles develop from special nucleated cells, the erythroblasts. It is believed that the latter gradually assume the form and color of perfect erythrocytes. Accord- ing to Neumann they possess blood coloring-matter from the outset. In caudate amphibia and fish the spleen, and in all other vertebrates, the bone-marrow constitutes the seat for the formation of those juve- nile forms that multiply by division. Particularly in the latter all stages of the transformation may be seen, especially pale, contractile cells resembling white blood-corpuscles, and later on red nucleated corpuscles that must be considered as the progenitors of the red corpuscles and that are capable of undergoing multiplication by mitosis. After copious loss of blood the process of transformation and the entrance into the blood-stream is said to be observed in especially marked degree. J. Arnold found in the protoplasm of the nucleated erythrocytes of bone-marrow granules resembling those of hemo- globin-free cells. In the process of transformation into red blood- corpuscles these granules become invisible through transformation. The products of the mitotic division of the pale cells especially are to be considered as the progenitors of the nucleated erythrocytes. In the red bone-marrow, perhaps also in the spleen, the small veins and most of the capillaries have no definite wall. The formed erythrocytes accord- ingly can at any time be swept into the circulation from these parts. The bones of the skull and most of those of the trunk contain red (blood- forming) marrow, while the extremities contain only fatty marrow, or only the upper portions of the femur and the humerus contain red marrow. When active regenerative processes are taking place in the blood the fatty marrow may be transformed into red marrow, and indeed from the upper portion of the bones named downward, even through all the bones of the extremities. Red, blood- corpuscle-forming marrow may develop even in the ossitk-d laryngeal cartilages and in pathological bony tumors. DESTRUCTION OF RED BLOOD-CORPUSCLES. As erythrocytes are being constantly formed, it must be assumed that they are being constantly destroyed. Further, the situations are known in which this occurs especially. Among these is first the liver, as the elements of the bile are formed from blood coloring-matter and the blood of the hepatic veins contains a smaller number of red blood-corpuscles. The splenic pulp also contains cells indicative of 44 DESTRUCTION OF RED BLOOD-CORPUSCLES. disintegration of erythrocytes. These are the blood-corpuscle-con- taining cells described in connection with the spleen. The investigations of Quincke have rendered it probable that the red blood-corpuscles whose span of life may cover more than three or four weeks if they are to be eliminated are taken up by the white blood-corpuscles of the liver-capillaries and by perhaps identical cells of the splenic pulp and of the bone-marrow, and preferably deposited in the liver-capillaries, the spleen, and the bone-marrow. The erythrocytes taken up are, without having previously been dissolved, converted in part into yellow and in part into colorless iron-albuminates, hematosiderin, which can be demonstrated microchemically in part in granular, in part in soluble form, giving rise to a greenish discoloration on addition of ammonium sulphid. In the spleen and in the bone-marrow, in part perhaps also in the liver, these are again employed for the regeneration of red blood-cor- puscles, while another portion of the iron is eliminated through the liver. Latschenberger has found pigmented and colorless plates in the blood, the latter at times in flakes of fibrin, and these he considers as the terminal prod- ucts of the disintegration of all morphological blood-elements. The pigmented plates are derived from the erythrocytes and exhibit in part the iron-reaction of hematosiderin, and in part that of biliary coloring-matter. These plates are retained and further transformed in the spleen and in the bone-marrow. As a sign of the degeneration of the erythrocytes that may precede their death Ehrlich mentions their property of staining violet with eosin-hematoxylin or blue with methylene-blue. The rarity with which cells containing blood-cor- puscles are found in the general circulation justifies the conclusion that corpuscles are taken up within the spleen, the liver, and the bone-marrow, being favored by the slowness of the circulation in these parts. Pathological. Among pathological conditions there may be quantitative dis- turbances in the processes of blood-destruction and blood-formation. Accumula- tion of iron-containing materials from red blood-corpuscles may take place in the spleen, the bone-marrow, and the liver-capillaries: (i) if the destruction of red blood-corpuscles is increased, as, for instance, in cases of anemia; (2) if the for- mation of new red elements from old material is retarded. If elimination through the liver-cells is interfered with, the iron accumulates in them, and it is then present in the blood-plasma also in increased amount, and it may be eliminated by other glands, although a deposit of iron may take place in these (cortex of the kidney, pancreas) within the glandular cells and in the tissue-elements of other organs. After abundant regeneration of blood in dogs the leukocytes of the liver- capillaries are in the course of four weeks enormously rich in iron-containing granules; likewise the cells of the spleen, of the bone-marrow, of the lymphatic lands, further the liver-cells and the epithelium of the cortex of the kidney. he iron-reaction in the two situations last named takes place also after intro- duction of hemoglobin or of iron-salts into the blood. Within thrombi and also in extravasations of blood that diffuse into the sur- rounding living tissue hematosiderin likewise develops, in addition to hematoidin, which forms when not in contact with the tissues. The stage of iron-reaction of the products of the disintegration of the erythrocytes is, however, not of con- sequence, as in the progress of time the residuum no longer exhibits this reaction. V. Recklinghausen designates as hemochromatosis a brownish discoloration of the tissues dependent upon abnormal dissolution of erythrocytes or local extrava- sations of blood, and which is caused by the iron-containing hematosiderin and the iron-free hemofuscin derived from it. Landois observed these conditions after extensive transfusion. If it be remembered that after repeated copious loss of blood and after every menstruation the blood is regenerated within a relatively short period of time, it is evident that an active process of regeneration must take place. As to the amount of corpuscles destroyed daily the amount of biliary and urinary pigment formed from the blood coloring- matter affords some idea. THE WHITE BLOOD-CORPUSCLES. 45 THE WHITE BLOOD-CORPUSCLES (LEUKOCYTES), THE BLOOD- PLATES AND ELEMENTARY GRANULES. Through the lymph-stream colorless cells, designated white blood- corpuscles or leukocytes, are swept into the blood. In addition to the blood they are found in the lymph, in adenoid tissue, in bone-marrow and as wandering cells in the connective tissues of various parts, as well as between glandular and epithelial cells. They consist of globular masses of viscid, bright or granular, highly refracting, soft, motile, unencapsulated protoplasm (Fig. 6). In the fresh state (A) they exhibit no nucleus, which appears only after addition of water or acetic acid (B), and in consequence of which also the definition becomes more distinct. Water, besides, renders the contents more granular and more turbid, while acetic acid causes them to clear up. The nucleus contains one or more nucleoli. The diameter of the cells varies from 4 to 13 //. The leukocytes are dissolved by peptone. In accordance with their form and size leukocytes are differentiated as follows: (i) Small lymphocytes, approximating erythrocytes in size, with a large, round, deeply staining nucleus and a thin margin of proto- plasm. (2) Large cells, with an extensive oval, feebly staining nucleus and a heavy cortical layer of protoplasm. " ^. (3) Cells resembling those jg^ HP last described except that the nucleus is constricted. (4) Somewhat smaller cells, con- stituting about three-quar- FlG 6 _ A) human white ^00^0^,^, wit hout any re- terS Of the total number, agent; B, after the action of water; C, after acetic acid; . , , , 111^-1 D. frog's corpuscles, changes of shape due to ameboid with polymorphous, lobulated movement, or variously convoluted nu- clei, or nuclei separated into from one to four parts. The last three forms of cells have a genetic connection. The leukocytes increase by division, in part by mitosis, in part by amitosis especially in their germ-centers, that is, the lymphatic glands and adenoid tissues. Division has not as yet been observed in the small lymphocytes found in the lymphatic glands (Fig. 8,00). Perhaps these represent juvenile forms. Also sessile cells in the^ connective tissue may undergo multiplication by division and send their offspring into the blood through the lymph-stream. The number of leukocytes in a given division of the vascular system may differ widely. At times they may be found increased in one place or another, as, for instance, as a result of chemotaxis, while at other times a large number may be sent into the blood-stream from the lymphatic apparatus. The increase is designated leukocytosis. The number of leukocytes is considerably less in shed blood than in circulating blood. Immediately after removal from the vessels nine- tenths of all of the leukocytes are destroyed (fibrin-formation). Local heat diminishes, and cold increases, the number of leuko- cytes in the vessels of the part of the body treated, as they are re- strained in the blood-vessels contracted by cold. 4 6 THE WHITE BLOOD-CORPUSCLES. NUMBER OF LEUKOCYTES IN PROPORTION TO THE RED BLOOD- CORPUSCLES IN SHED BLOOD. UNDER NORMAL CONDITIONS. IN VARIOUS SITUATIONS. UNDER VARIOUS CONDITIONS. i 335, Welcker, i 357, Moleschott, i 500-800, v. Jaksch, (In children the number is said to be somewhat greater than in adults.) Splenic vein, i : 60, Splenic artery, i : 2260, Hepatic vein, i : 170, Portal vein, i : 740, The number is in general greater in the veins than in the arteries. The number is increased by digestion, blood-let- ting, long-continued suppuration, menstru- ation, the puerperium, the death-agony, tonic medicaments (quinin, bitters) , ingestion of nuclein, gout. The number is dimin- ished by hunger and impaired nutrition. The movement of the leukocytes observed by Wharton Jones in 1846 in the ray, and by Davaine in 1850 in man which has been desig- nated ameboid, because it corresponds entirely with that of the ameba, is due to alternate contraction and relaxation of the protoplasm surrounding the nucleus. It can be recognized especially from the fact that processes are sent out from the surface and withdrawn (Fig. 7) like the pseudopods of the ameba. At the same time the protoplasm has an internal current, which can be seen particularly in the polymor- phonuclear cells. Movement has been seen also in the nucleus itself. The movement is attended with two sets of phenomena: (i) The migra- tion of the cells, inasmuch as they draw themselves along by means of protrusion and retraction of their viscid processes. In this way they may migrate even through the interstices of intact vessels. Arnold considers the capability of certain wandering cells to develop into epithelioid or giant cells as demonstrated. (2) The taking up of small granules, such as fat, pigment, foreign bodies, which at first adhere to the surface and through the internal current are drawn into the interior of the leukocytes and which filially may be again extruded, in the same way as amebae take up food. Thus they take up fat-globules, peptones and albuminous bodies that have gained entrance into the blood-stream and which they may later deposit elsewhere. Metschnikoff dwells upon the activity of the leukocytes in retrogressive pro- cesses, the parts to be broken down being taken up in the forms of particles and therefore in a measure devoured. He designates the cells with these activities as devouring cells phagocytes. Thus they act as chondroclasts and osteoclasts in the absorption of cartilage and bone respectively. Cells of similar activity are found in the tails of batrachia, and which take up portions of the tissue, as, for instance, fragments of fibrils, in the disappearance of the tails during the process of metamorphosis. (See also absorption of the deciduous teeth.) Thus, schizomycetes or particles of other substances that have gained entrance into the blood have been found taken up in part by leukocytes. Later, the leu- kocytes yield up these substances to the endothelial cells of the capillaries of the liver and the lungs, less commonly of the spleen. The motility of the leuko- cytes is destroyed by quinin. The leukocytes exhibit still another interesting peculiarity, namely that of chemotaxis (chemotropism) , which consists in the attraction of freely motile cells like some lower organisms by certain substances, and their repulsion by certain others. Especially the metabolic products of pathogenic and non-path- ogenic microorganisms exert a strong attractive influence upon the leukocytes. HUMAN LEUKOCYTES, SHOWING AMEBOID MOVEMENTS. 47 If, therefore, colonies of staphylococcus (bacteria of suppuration) collect at a given part of the body their metabolic products attract the leukocytes from the neighbor- ing vessels, and in this way inflammatory reaction and suppuration result. The poison is either eliminated with the pus or is destroyed by the phagocytic activity of the leukocytes. The leukocytes also secrete special chemical substances that destroy the injurious microorganisms. These substances are known as alexins. In warm-blooded animals the leukocytes exhibit movement for a long time upon a warm stage at a temperature of 40 C. for about two or three hours; a temperature of 47 C. induces rigidity: heat-rigidity and death. The lowest degree of temperature at which ameboid move- ment is possible is 14 C. In cold-blooded animals, such as the frog the leukocytes can be seen to make their way out of a small coagulated blood-clot in a moist chamber and move about in the express- ed serum, v. Reck- linghausen observed motile phenomena on the part of leukocytes in a moist chamber for as long as three w r eeks. Oxygen is necessary for the moA r ement. Induc- tion-currents cause the leukocytes sud- denly to become round, like irritated amebae through re- traction of all of their processes. If the electric current be not too strong, the leuko- cytes resume their movements in the course of a short time. Strong and long-continued currents destroy them, causing them further to swell and undergo complete disintegration. The dissolution of white blood- corpuscles is known as leukocytolysis . It occurs as a normal phenom- enon in the circulating lymph and in the blood in limited degree. With regard to the -source and the functional significance' of the different varieties of leukocytes complete knowledge is as yet wanting. An attempt has been made to obtain a sharper differentiation of the leukocytes through the property of the smallest granules within the protoplasm of the cells to stain only with acid or with basic or with neutral pigments. Method. Recently shed blood is spread in a thin layer upon a cover-slip, dried in the air, then placed in an air-bath at a temperature of i25C. for two hours. Next it is stained, washed with water, dried in the air and enclosed in Canada balsam. The granules of the oxyphile or eosinophile cells (Fig. 8, a,b, with unstained nucleus; "in c the nucleus is stained violet with hematoxylon) are stained only by acid pigments, such as a saturated solution of eosin in 5 per cent, carbolglycerin. The source of these cells is the bone-marrow. In normal human blood they con- stitute only about 10 per cent, of all of the leukocytes, but in cases of leukemia they pass in large number from the bone-marrow into the blood-stream -myel- ogenous leukemia. The fine granules of the large mononuclear cells of normal blood are stained only by basic pigments, such as a concentrated watery solution of methylene-blue (f, g), as well as those of the majority in lymphemic blood. The cells known as mast-cells contain basophile granules of other size (d, e). These cells are rare in normal blood, but they often occur in large number in leukemic blood. Mast- FIG. 7. Human Leukocytes, Showing Ameboid Movements. 4 8 VARIOUS FORMS OF LEUKOCYTES AND ERYTHROCYTES. cells may be found also in the connective tissue of other organs in the vicinity of the epithelial layer, as, for instance, in cutaneous areas the seat of chronic inflammation, and from which they then find their way into the blood. Fine neutrophile granules are rendered visible by neutral stains, as, for instance, acid fuchsin neutralized with methylene-blue. These cells exhibit peculiarly sharp, polymorphous nuclear figures (h) or apparently several small nuclei. They are encountered in abundance in normal blood and in the presence of leukocytosis (i is such a cell in the fresh state, while in k and 1 the nucleus alone is stained). The smaller number of neutrophile cells contain a large nucleus, surrounded by a thin layer of protoplasm (m n) . They are derived from the spleen and the bone- marrow. Between these two forms (h and m n) there are transitional varieties. The leukocytes h i migrate in the presence of inflammation. In cachectic states the mononuclear cells (m n) preponderate, while both forms are increased in num- ber in association with acute leukocytosis. The lymphocytes o o, with a large reticulated nucleus, are derived from the lymphatic glands. Neusser found numerous granules of nucleoalbumin in the leukocytes in cases of gout as the forerunners of uric-acid formation. The leukocytes exhibit the reac- tion for glycogen in the presence of progressive suppuration. FIG. 8. Various Forms of Leukocytes and Erythrocytes. X 1000. [All figures are drawn after the same scale: i, a normal erythrocyte drawn into the scale; i = i /u-.] The blood-plates of Bizzozero (Fig. 9) deserve especial consideration as a third morphological constituent of the blood. These are pale, color- less, viscid, biconcave discs of varying size, averaging 3 P. in diameter. One cu. mm. contains 245,000 plates. Bizzozero has observed them in the circulating blood in the mesentery of the guinea-pig and the wing of the bat. They collect in large numbers upon a thread immersed in fresh blood. They can be obtained from escaping blood after ad- mixture with one per cent, solution of osmic acid or with Hay em's fluid (Fig. 9, 3). In shed blood they rapidly undergo transformation into varied shrunken forms (5), disintegrating into small particles and THE BLOOD-PLATES. 49 being finally dissolved. Where they are collected together they readily cohere into masses (7), and pass over into aggregations resembling stroma-fibrin, which in coagulated blood may be united with shreds of fibrin (6, 8). Bizzozero believes that they furnish the material for the fibrin in the process of coagulation, and he, as well as Eberth and Schimmelbusch, attribute the initial formation of white thrombi to them. According to Lowit they are formed from disintegrated leukocytes, and according to Lilienfeld from the nuclein and albumin of the nuclei of these cells. According to Wooldridge they are globulin-precipi- tates from the plasma. J. Arnold followed their extrusion and detachment from ery throcy tes ; in smaller measure they are derived from leukocytes. Halla found them increased in pregnant women, Mosen after hemorrhage, Afanassiew in the presence of regenerative states of the blood, Cadet in association with hunger, Hayem after the crisis of certain infectious diseases, and Fusari in cases of afebrile anemia. They are diminished in the presence of fever, as well as of severe infec- tions and blood-stasis, and also after injection of leech-extract. The blood of cold-blooded animals and of birds contains also small spindle-shaped, nu- cleated cells. FIG. 9. "Blood-plates" and Their Derivatives: i, a red blood-corpuscle on the flat; 2, on the side; 3, unchanged blood-plates; 4, lymph corpuscle, surrounded by blood-plates; 5, altered blood-plates; 6, lymph corpuscle with two heads of fused blood-plates and threads of fibrin; 7, group of fused blood-plates; 8, small group ot partially dissolved blood-plates with fibrils of fibrin. Demonstration in Mass. If 10 parts of blood are mixed with i part of a 0.2 per cent, solution of ammonium oxalate in 0.7 per cent, solution of sodium chlorid, and the mixture is centrifugated, a grayish-red layer principally of leukocytes will form above the ery throcy tes, and over this a white layer consisting almost solely of blood-plates, while above all is the clear plasma. In addition, a few small granules, so-called elementary granules, occur in the blood. These are irregular masses of protoplasm derived from disintegrated leukocytes or blood-plates. According to H. F. Miiller there are constantly present also, especially after the ingestion of food, minute, globular, highly refracting granules, which are not fat, and which he designates blood-dust, or nemokonien. Coagulated blood contains delicate threads of fibrin (Fig. 9, 6, 8), strung like a spider's web between the corpuscles. They become iso- lated after dissolution of the corpuscles. Where many such threads occur together a nodular accumulation takes place. 50 ABNORMAL CHANGES IN RED AND WHITE BLOOD-CORPUSCLES. ABNORMAL CHANGES IN THE RED AND WHITE BLOOD- CORPUSCLES. Loss of blood is always followed by diminution in the number of erythrocytes in proportion to the extent of the hemorrhage, and the number may fall to even less than 400,000 in the cu. mm. The loss is soon made good by the absorp- tion of lymph from the tissues. Menstruation furnishes an indication that moderate loss of red blood-corpuscles may be replaced in twenty-eight days. In case of considerable loss of blood, causing a reduction in all of the formative processes, this period may be prolonged to five weeks. In cases of acute febrile disease the elevation of temperature is generally attended with a reduction in the number of red blood-corpuscles, though with an increase in the number of white corpuscles. Chronic diseases diminish the number and often the hemoglobin-con- tent of the erythrocytes in still greater degree. In some individuals, in whom the red blood-corpuscles are deficient in resistance, these undergo dissolution in consequence of the action of profound cold upon peripheral portions of the body, as, for instance, from the application of ice-water, while the blood-plasma becomes reddened and hemoglobinuria may even develop. Diminished regenerative activity on the part of new erythrocytes will also cause reduction in their number, as blood-corpuscles are constantly undergoing destruction. If with this there be associated direct loss of blood, as, for instance, menstruation, the reduction may become considerable. In the case of chlorosis a congenital deficiency in the development of the blood-forming and blood-pro- pelling apparatus, that is the vascular system, appears to constitute the cause. The heart and the vessels are small, and the absolute number of blood-corpuscles may be reduced even one-half. In the blood-corpuscles themselves, whose relative number may be either maintained or even reduced as much as one-third, the hemo- globin is reduced about one-third. The total volume of erythrocytes has been found diminished. The iron-content of the blood has been reduced, even to one- half. Courses of treatment with iron again increase the amount of hemoglobin and iron in the blood. So-called progressive pernicious anemia, which is char- acterized by the fact that the progressive impoverishment of the blood may even finally terminate fatally, is probably dependent upon some profound derange- ment of the blood-forming organs. In the presence of this disease the erythro- cytes are reduced in number, while their hemoglobin-content is increased. Invo- lution-forms, disintegrat ing-products (microcytes and poikilocytes) and earlier developmental stages of erythrocytes (nucleated erythrocytes of normal and of excessive size : normoblasts and megaloblasts) are also present . Numerous chronic intoxications, as with lead, swamp -miasm or syphilis, are likewise attended with reduction in the number of blood-corpuscles. The size of the corpuscles varies in disease between 2.9 and 12.9 //, with an average size of from 6 to 8 //. Dwarf blood-corpuscles (6 i* and below, microcytes) have been considered as juvenile forms and are found in abundance in almost all forms of anemia (Fig. 8, 6). Giant corpuscles (megalocytes, 10 n and above) are found constantly in cases of pernicious anemia, occasionally in cases of leuke- mia, chlorosis, and cirrhosis of the liver (Fig. 8, 4, 5, represents a nucleated megalocyte as the forerunner of a non-nucleated megalocy te) . If the erythrocytes exhibit marked variation in form and size, they are designated poikilocytes (Fig. 8, 6). Abnormalities in the form of the red blood-corpuscles have been observed after severe burns. The corpuscles appear much reduced in size and the thought sug- gests itself that under the influence of the heat accompanying the burn droplets of the corpuscles have become detached, in the same way as this can be ob- served in microscopic preparations on application of heat. Disintegration of blood-corpuscles in many such droplets (erythrocytotrypsy) has been observed in connection with various disorders, as, for instance, severe malarial fevers. These particles represent fragments of blood-corpuscles and not independent, intact, small, individual corpuscles. From these fragments there result dark pigment-particles closely related to hematin and which at first float about in the blood (melanemia) . This condition can be developed artificially in rabbits by introducing carbon disulphid (7 parts to 90 parts of oil) subcutane- ously. The leukocytes take up a number of these particles, which later on are found deposited in various tissues, particularly the spleen, the liver, the brain, and the bone-marrow. In some cases the red blood-corpuscles exhibit abnormal softness, so that they CHEMICAL CONSTITUENTS OF THE RED BLOOD-CORPUSCLES. 51 undergo marked changes in form as the result even of slight extraneous influences. With regard to lessened, resistance on the part of the erythrocytes, reference may be made to p. 35. The nitrogen-content of the erythrocytes is diminished in cases of secondary anemia, and it is increased in cases of pernicious anemia. In the interior of the erythrocytes of birds, frogs, turtles, etc., low forms of animals develop at times in the form of round pseudovacuoles, and out of which free blood-worms subsequently develop. Also in cases of malarial infection in human beings microbes of varying form (hemameba, Lavcran) have been observed within the erythrocytes, and which probably are conveyed by stinging insects (mos- quitos) in the same way as Texas fever is conveyed by ticks. They destroy the red blood-corpuscles and in turn are destroyed by quinin. The white blood-corpuscles are generally increased 1 in all acute diseases in which exudation takes place. They exhibit excessive increase in association with so-called leukemia. In this disease the proportion of red to white blood- corpuscles may be as 2 to i. In consequence, the blood acquires an appear- ance as if it were mixed with milk. At the same time the number of erythrocytes is diminished. Leukemia depends upon hyperplasia of the lymphoid tissue or the bone-marrow. These causes are responsible for lymphatic and myelogenous leukemia respectively. Lymphocytes and myelocytes are to be carefully differentiated. The enlargement of the spleen is only secondary; there- fore a pure variety of lienal leukemia is not accepted. Myelogenous leukemia belongs probably among the active forms of leukocytosis. An active leukocytosis is one that results through movement or migration of leukocytes into the blood- current. This may involve the polynuclear neutrophile or eosinophile or the mixed cells the latter with involvement of mononuclear elements containing granules: myelemia. The passive form of leukocytosis comprises the various forms of lymphemia. CHEMICAL CONSTITUENTS OF THE RED BLOOD-CORPUSCLES. The blood coloring-matter hemoglobin abbreviated Hb causes the red color of the blood. It is found besides in muscular tissue and in traces, probably only as a contamination through dissolved cells, in the blood-plasma. In the spectroscope it exhibits an absorp- tion-band in the green (Fig. 15, 4). Its percentage-composition ac- cording to Hiifner is for the blood of swine, as compared with that for the ox, in parentheses, C, 54.71 (54-66); H, 7.38 (7.25); N 17.43 (17.70); S, 0.479 (o-447); Fe, 0.399 (0.336); O, 19.602 (19.543). For one atom of iron there are two atoms of sulphur in the horse, and three in the dog. According to Hufner, the formula is C 6 3 6 H 1025 N 164 FeS 3 O 181 ) ; the molecular weight is 14,129. Hemoglobin is soluble in water; when heated it coagulates only with decomposition, retaining the sulphur in firm union. Although it is a colloidal substance, it nevertheless undergoes crystallization in all classes of vertebrates from which it has thus far been obtained, in figures belonging to the rhombic system, principally in rhombic plates or prisms, and from the guinea-pig in rhombic tetrahedra. The squirrel, however, forms an exception, in- asmuch as its crystals appear as hexagonal plates. The crystals simply separate in all classes of vertebrate after slow evaporation of blood rendered lake-colored, though with varying degrees of readiness. It is to be inferred that the variations in the form of the crystals in different animals are dependent upon slight changes in chemical constitution. The hemo- globin is readily crystallized from the blood of man, the dog, the mouse, the guinea- pig, the rat, the marmot, the cat, the leech, the horse, the rabbit, birds, and rish; and with difficulty from the blood of sheep, oxen, and swine; and not at all from the blood of the frog. Rarely the hemoglobin of a single blood-corpuscle can be seen to form a small crystal with inclusion of the stroma, as Landois also ob- served in the case of rabbits' blood that had stood for a long time. Within the large blood-corpuscles of fish the small crystal lies at times within the stroma by the side of the nucleus. In this class of vertebrates colorless crystals also have at times been observed. 5 2 PREPARATION OF HEMOGLOBIN-CRYSTALS. The crystals of hemoglobin are doubly refracting and pleochromatic, that is, they appear bluish red in transmitted light and scarlet red in reflected light. The crystals, which contain from 3 per cent, to 9 per cent, of water of crystallization and therefore become disintegrated from es- cape of this water on exposure to the air, are always soluble in water, though different varieties dissolve with varying degrees of facility. They are more readily soluble in dilute alkali. The solutions are dichroic, that is, they ap- pear red in reflected light and greenish in transmitted light. They are insolu- ble in alcohol, ether, chloroform, and fats. As a result of the process of crystalliza- tion the hemoglobin itself appears to under- go an internal change. Previous to crystal- lization it does not diffuse as a true colloidal body;, but it actively decomposes hydrogen dioxid. Dissolved in the form of crystals, however, it is slightly diffusible, and does not decompose hydrogen dioxid, through the action of which it is decolorized. The crys- tals of hemoglobin collect like an acid at the positive pole of an electric current. As the hemoglobin thus exhibits alterations after its separation from the erythrocytes, Hoppe- Seyler believed that the oxyhemoglobin was united with lecithin within the erythrocytes, and also the hemoglobin. The former 'combination he designated arterin and the latter phlebin. FIG. 10. Hemoglobin-crystals: a b, from hu- man blood; c, from the cat; d, from the guinea-pig; e, from the marmot; and f, from the squirrel. PREPARATION OF HEMOGLOBIN-CRYSTALS. Method of Rollett. Defibrinated blood, made lake-colored by freezing and thawing, is poured into a shallow vessel, whose bottom is covered therewith to a height of only i mm. Evaporation is permitted to take place slowly in a cool place and as a result the crystals separate. Method of Hoppe-Seyler. Defibrinated blood is mixed with 10 volumes of a solution of sodium chlorid or of sodium sulphate (i volume of a concentrated solution to 9 volumes of water) and permitted to stand. After the lapse of two days the clear supernatant layer is removed with a pipet, while the thick sediment of blood-corpuscles is washed with water into a glass flask, and shaken with an equal volume of ether until the blood-corpuscles are dissolved. After standing for a short time the supernatant ether is removed, and the lake-colored fluid filtered in the cold; then one-fourth volume of cold (o) alcohol is added. This mixture is permitted to stand for several days at a temperature of 5 C. The crystals that will thus have formed in abundance can be collected upon a filter and dried by pressure between blotting-paper. Through the gradual action of the alcohol upon the hemoglobin-solution, by introduction into a dialyzer, it is possible to obtain crystals several millimeters long. Method of Gscheidlen. Gscheidlen obtained the largest crystals, several centi- meters in length, by melting in small glass tubes defibrinated blood that had been exposed to the air for 24 hours, and preserving for several days at a tem- perature of 37 C. Spread upon a glass plate the crystals readily appear. QUANTITATIVE ESTIMATION OF THE HEMOGLOBIN. (a) From Its Iron-content. As in the dry state (100 C.) hemoglobin contains 0.42 per cent, of iron by weight, the amount of hemoglobin can be estimated from the amount of iron in the blood. If m represents in percentage the weight QUANTITATIVE ESTIMATION OF THE HEMOGLOBIN. 53 of metallic iron found, the percentage of hemoglobin in the blood will be as 100 m : 0.42. The mode of procedure is as follows: A measured amount of blood is reduced to ash and this is exhausted with hydrochloric acid for the preparation ot tcrnc chlond. Next the ferric chlorid is converted into ferrous chlorid and this is titrated with a solution of potassium permanganate. (6) Colorimelric Method. A dilute watery solution of crystallized hemoglobin is prepared, the exact strength of which is thus known. With this are compared watery dilutions of the blood to be examined, water being added to the latter until the color is the same as that of the hemoglobin-solution. The specimens to FIG. ii. -V. Fleischl's Hemometer. To wash out the graduated pipet the larger tube held over it is employed. be compared are contained in similar vessels of exactly the same thickness (hema- tinometer). Hoppe-Seyler has recently devised a colorimetric double pipet for this purpose. The blood-specimens are saturated with carbon monoxid. For clinical purposes v. Fleischl's hemometer is recommended (Fig. n). This consists of a cylinder mounted upon a metallic plate and divided into two equal parts, which are closed at one extremity by a disc of glass. Each half is filled with water, and then a measured amount of blood, obtained with a pipet of deter- mined capacity from a punctured wound, is introduced into the one half and dissolved. The color of the red solution thus produced is compared with that of a ruby-red glass wedge viewed through the clear water in the other half of the cylinder and capable of being moved forward and backward by a screw, until 54 EMPLOYMENT OF THE SPECTROSCOPE. the color appears the same in both. The illumination of the blood-solution and the red wedge takes place from below by means of the light of a lamp. The glass wedge is provided with a scale, and when the colors in the two halves of the cylinder are alike the number on the wedge indicates the amount of hemo- flobin in terms of percentage of the normal blood; thus, for instance, the figure o indicates that the examined blood contains 80 per cent, of the hemoglobin in normal blood. (c) With the aid of the spectroscope Preyer found that a solution of 0.8 per cent, of pxyhemoglobin in water i cm. thick yielded in addition to red and yellow the first band of green in the spectroscope (Fig. 15, i). Of the blood to be examined about 0.5 cu. cm. is taken and is diluted with water until the identical of effect in the spectroscope is obtained. In addition to having the layers of fluid equal thickness namely i cm. the width of the slit in the spectroscope and the dis- tance between this and the vessel, as well as the intensity of the source of light (stearin candle), must be the same. If k represents the amount of hemoglobin in percentage that permits the passage of the green color (0.8 per cent.), and b the volume of blood to be examined (about 0.5 cu. cm.), and w the amount of water necessary for dilution, then x equals the amount of hemoglobin in the blood to be examined expressed in percentage, that is x =k (w+b) : b. It is advantageous to add a trace of potassic hydrate to the blood and to saturate it with carbon monoxid. The amount of hemoglobin is in men 13.77 per cent, of the total volume of blood, in women 12.59 per cent., in pregnant women with progressive diminution from 12 to 9 per cent. According to Lichten- stern and Winternitz the hemoglobin is most abundant in the blood of the newborn, but this is no longer the case after the age of ten weeks. Between six months and five years of age it is smallest in amount and reaches its second maximum between twenty-one and forty-five years, after which it falls again. The hemoglobin in female blood grows less after the tenth year. The ingestion of food is followed by transitory diminution in the amount of hemoglobin in consequence of the dilution of the blood. The amount of hemoglobin in different animals is as follows: 9.7 per cent, in the dog; 9.9 per cent, in cattle; 10.3 per cent, in sheep; 12.7 per cent, in swine; 13.1 per cent, in the horse, and from 1 6 to 17 per cent, in birds. In moist erythrocytes Hoppe-Seyler found the hemoglobin to con- stitute 40.4 per cent, of all the organic elements, while in the dry cor- puscles the amount was 95.5 per cent., the amount being smaller in the nucleated corpuscles of animals. Pathological. A reduction in the amount of hemoglobin in the blood takes place during convalescence from febrile diseases, as well as in the presence of pulmonary tuberculosis, carcinoma, ulcer of the stomach, diseases of the heart, chronic disease, chlorosis, leukemia, pernicious anemia, and in conjunction with vigorous mercurial treatment for syphilis. In the presence of hunger the hemo- globin is more resistant than the remaining solid elements of the blood. EMPLOYMENT OF THE SPECTROSCOPE FOR HEMOGLOBIN EXAMINATION. The spectroscope (Fig. 12 and Fig. 161) consists (i) of a tube A, having at its peripheral extremity a slit S, which can be made larger and smaller. At the other extremity is a double convex lens C, known as a collimator, so adjusted that the slit is placed exactly at the focus of this lens. Light, from the sun or a lamp, illuminating the slit, passes therefore in parallel lines through C. (2) The prism P, by means of which parallel rays are refracted and broken up into the spectral colors, r-v. An astronomic telescope, inverting the image, is directed toward the spectrum r-v, which appears magnified from 6 to 8 times to the view of the observer B with the aid of the telescope. (3) The tube O contains a delicate scale M etched upon glass, and the image of which when illuminated is thrown upon the surface of the prism, whence it is in turn reflected to the eye of the OXYGEN-COMBINATIONS OF HEMOGLOBIN. 55 observer. In this way the observer can see the spectrum and in or over it the scale. To exclude extraneous, disturbing light, the prism and the inner extremities of these tubes are enclosed within a metallic capsule whose interior is colored black. Absorption-spectra. If a colored medium, as, for instance, a solution of blood, be placed between the slit of the spectroscope and a source of light, the interposed solution does not permit the passage of all of the rays of white light, but some of these are absorbed. Therefore, that portion of the spectrum whose rays are not permitted to pass appears dark to the observer. FIG. 12. Diagrammatic Representation of the Spectroscope for Study of the Absorption-spectra of the Blood. Flame-spectra. If combustible substances are permitted to burn before the slit in a non-luminous (gas) flame at the extremity of a platinum wire the elements of the ash yield bands of a special color occupying a definite position. Thus, sodium gives rise to a yellow, potassium to a red and a violet line, which are found on combustion of the ash of almost all organs. If sunlight alone is permitted to pass through the slit the spectrum exhibits a large number of lines (Fraun- hofer's lines) occupying definite positions within the colors and according to which different parts of the spectrum can be localized. These are designated A, B, C,|D, etc., a, b, c, etc. (Fig. 15). OXYGEN -COMBINATIONS OF HEMOGLOBIN: OXYHEMOGLOBIN AND METHEMOGLOBIN. Oxygen-hemoglobin or Oxyhemoglobin abbreviated to O-Hb is read- ily developed when hemoglobin comes in contact with oxygen or with air (details on p. 78). Oxyhemoglobin is somewhat less readily soluble than hemoglobin. On spectroscopic analysis it exhibits two dark absorption-bands in the yellow and the green, whose position and width in an 0.18 per cent, solution are shown in Fig. 15 (2). Oxyhemoglobin is contained within the erythrocytes in the circu- lating blood of the arteries and capillaries, as may be demonstrated by spectroscopic examination of the ear of the rabbit and of the thin layers of skin between two fingers placed in apposition. It is an exceedingly unstable chemical combination, yielding its oxygen even through the influence of such agents as release absorbed gases, as, for instance, setting free of gas through the action of an air-pump or the passage of other 56 OXYGEN-COMBINATIONS OF HEMOGLOBIN. gases, particularly carbon monoxid, and heating to the boiling-point. Also in the circulating blood the oxygen is readily given up to the tissues of the body, so that in animals dead from suffocation only gas-free reduced hemoglobin is found in the veins. Also con- stituents of the serum and sugar remove the oxygen. By addition of reducing substances to a solution of oxyhemoglobin, as, for instance, ammonium sulphid, the two bands of oxyhemoglobin disappear and reduced gas-free hemoglobin results (Fig. 15, 4). This is recognizable from its wide ill-defined absorption-band. Agitation with air, how- ever, at once restores both bands through the formation of oxyhemo- globin. Solutions of oxyhemoglobin are readily distinguished by their scarlet color from the wine- violet-red tint of reduced hemoglobin. The yellowish-green color of the solar spectrum thrown isolated upon the closed upper eyelid causes a sensation of dark. If the base of two fingers be ligated to the point of interrupting the circulation it will be seen on spectro- scopic examination of the intervening red cutaneous seam that the oxyhemo- (X9 aBC Eb F FIGS. 13 and 14. The Absorption-spectra of Oxyhemoglobin (Fig. 13) and of Gas-free Hemoglobin (Fig. 14 ) with Increasing Concentration. The letters of the lower line indicate the Fraunhofer lines. The figures at the side indicate the percentage-strength of the solutions (after Rollett). globin is soon transformed into reduced hemoglobin. This reaction is delayed under the influence of cold; it is accelerated in youth, during muscular activity or with suppression of breathing and generally also in the presence of fever. A beating heart also exerts a reducing influence upon oxyhemoglobin. The absorp- tion-spectra naturally vary with the concentration of the solution ; in the presence of a greater amount of hemoglobin the bands are wider and may become confluent, and finally the largest part of the spectrum may thus become dark. Figs. 13 and 14 show how the absorption -bands appear in solutions of varying strengths: from a i per cent, solution (above) the concentration progressively diminishes down- ward by gradations of o.i per cent., until at O O the fluid is without hemo- globin. The thickness of the layers of fluid is placed at i cm. Spectroscopic examination of small blood-spots, possibly for medico-legal purposes, may be of the greatest importance. Often a minute spot is sufficient. Dissolved with one or two drops of distilled water it may be introduced longitu- dinally in a thin glass tube before the narrow slit of the spectroscope, and the two bands of oxyhemoglobin appear. Preserved in alcohol, oxyhemoglobin is transformed into a modification in- soluble in water but otherwise identical, namely parahemoglobin. OXYGEN-COMBINATIONS OF HEMOGLOBIN. 57 A second oxygen-containing isomeric, but chemically more stable crystallizable combination is methemoglobin, whose molecule contains the same amount of oxygen as oxy hemoglobin, but in different ar- rangement. Its spectrum closely resembles that of hematin in acid solution (Fig. 15, 5). The band toward the red is the heaviest, while the others are narrow and are in part designated as not characteristic. Demonstration. i. By oxidizing substances, such as ozone, potassium iodid, chlorates, nitrates. 2. By reducing substances, such as nascent hydrogen and pyrogallol. 3. By indifferent influences, such as prolonged heating or slow desic- cation of the blood. Potassium permanganate, potassium ferrocyanid and ferri- cyanid exert an intense effect, while nitrites transform the oxyhemoglobin into Red. Orange. Yellow. Green. Cyanid Blue. 110 Oxyhemoglobin 0.18 per cent. Oxyhemoglobin 0.18 per cent. Carbon-monoxid hemoglobin. Gas-free or reduced hemoglobin. Methemoglobin ; also hematin in acid solution. Hematin in alkaline solution. Hemochromogen in alkaline solution; also reduced hematin. A a FIG. 15. The Various Absorption-spectra of Hemoglobin. In all of the spectra the various Fraunhofer lines and a scale in millimeters are drawn. a mixture of methemoglobin and nitrogen-monoxid hemoglobin. Not alone lake-colored blood, but also the hemoglobin of intact erythrocytes may be transformed into methemoglobin, as, for instance, by potassium chlorate, antifebrin and other substances, and also by intoxication with these sub- stances. Often both conditions are present in combination. The occurrence of methemoglobin in solutions in the blood-plasma of a poisoned individual is designated methemo plasm ia, and the -occurrence of the methemoglobin in the pre- 58 CARBON-MONOXID 'HEMOGLOBIN. served blood-corpuscles methemacytosis. Lesser degrees of the latter may recede spontaneously in the body without destruction of the erythrocytes. Profound influences resulting in the production of methemoglobin destroy the blood- corpuscles and require transfusion. Preparation of Crystals. To the solution of isolated erythrocytes described on p. 37 is added double its volume of a concentrated solution of ammonium sul- phate, and evaporation is permitted to take place in the cold. There form brown- ish-red needles, prisms or plates with marked pleochroism. Methemoglobin develops in part spontaneously in the body, as, for instance, in bloody urine, in the sanguinolent contents of cysts, in old extravasates and in dried blood- crusts. The addition of a trace of ammonia to a solution of methemoglobin pro- duces an alkaline solution of methemoglobin, which exhibits two bands similar to those of oxyhemoglobin, but of which the first is the wider and extends the more toward the red. If a reducing solution of ammonium sulphid be added to solu- tions of methemoglobin, reduced hemoglobin develops. CARBON-MONOXID HEMOGLOBIN AND CARBON-MONOXID POISONING. Carbon-monoxid hemoglobin is a more stable combination than the preceding and is produced when carbon monoxid is brought into con- tact with hemoglobin or oxyhemoglobin. It is cherry-red in color, not dichroic, and it exhibits in the spectrum two absorption-bands that closely resemble those of oxyhemoglobin, but are somewhat closer together and more toward the violet (Fig. 15, 3). It can be readily recognized, however, from the fact that reducing substances, which influence the oxyhemoglobin, do not dissolve these bands, that is, do not transform the carbon-monoxid hemoglobin into reduced hemoglobin. A further means of recognition consists in the sodium- test: a 10 per cent, solution of sodium hydroxid added to carbon-mon- oxid hemoglobin and heated gives rise to a cinnabar-red color. The same solution added to oxyhemoglobin produces a black-brown- greenish mass. The spectrum-analytical examination and the sodium- test permit the recognition of three-tenths carbon-monoxid hemoglobin mixed with seven-tenths oxyhemoglobin. Carbon-monoxid hemoglobin reactions : Modified sodium-test: The blood is diluted 20 times and an equal amount of sodium hydroxid of a specific gravity of 1.34 is added in a test tube. Carbon-monoxid blood assumes a beauti- ful red color after addition of ammonium sulphid 2 grams of sulphur being added to 100 grams of yellow ammonium sulphid and 30 per cent, acetic acid, while normal blood assumed a greenish-gray coloration. Both kinds of blood exhibit also differences in color when treated as follows: Dilute potassic hydrate is added, and then a few drops of a watery solution of pyrogallic acid; the mixture is shaken at once and permitted to stand protected from the air. For the purpose of the test, blood made lake-colored with water may be used, as well as blood in which the erythrocytes are preserved by addition of concentrated solution of sodium sulphate. Three cu. cm. of blood are diluted with 1 1 oo cu. cm. of water; 10 cu. cm. of this are mixed with 2 cu. cm. of 2 per cent, solution of grape-sugar and 2 cu. cm. of saturated solution of barium carbonate or lime-water, and the whole is heated almost to the boiling-point. From 4 to 5 volumes of lead acetate added to the blood cause a distinct differ- ence accordingly as oxygen or carbon-monoxid blood is present. Oxidizing substances, as, for instance, solutions of potassium permanganate 0.025 per cent., potassium chlorate 5 per cent., and dilute chlorin-water, render solutions of carbon-monoxid hemoglobin cherry-red, while they render solutions of oxyhemoglobin pale yellow. Both varieties of hemoglobin thus treated acquire the bands of methemoglobin, the carbon-monoxid hemoglobin considerably later. Subsequent addition of ammonium sulphid transforms the forms of hemoglobin thus altered back again into oxyhemoglobin and carbon-monoxid hemoglobin. By reason of its greater constancy carbon-monoxid hemoglobin resists putre- faction for a long time, as well as the action o hydrogen sulphid. POISONING WITH CARBON MONOXID. 59 If carbon monoxid be inspired it gradually displaces, volume for volume, the oxygen of the hemoglobin, and death finally results; 1000 cu. cm. of carbon monoxid will kill human beings if breathed at once. Small amounts of carbon monoxid in the air (TTro~Trnnr) how- ever, suffice to generate comparatively large amounts of carbon-monoxid hemoglobin within a short time. As by means of long-continued treatment of carbon-monoxid hemoglobin with other gases, particularly oxygen, passing them through the carbon monoxid may be grad- ually again separated from the hemoglobin, with the re-formation of oxy hemoglobin, so in the body also the carbon monoxid is eliminated through the respiratory process in the course of a few hours, a por- tion of the carbon monoxid apparently being oxidized into carbon dioxid. Poisoning with Carbon Monoxid. Carbon rnonoxid results from incomplete combustion of carbon, as, for instance, through premature closure of stove-valves and badly smoking lamps. It occurs in illuminating gas in a proportion of from 12 to 28 per cent. As carbon monoxid has 200 times as great an affinity for hemoglobin as oxygen, more and more of the latter is displaced from the blood by the breathing of air containing carbon monoxid, and life naturally can continue only so long as sufficient oxygen is conveyed by the blood as is necessary to main- tain the processes of oxidization essential to life. Death occurs amid peculiar phenomena, even before all of the oxygen is expelled from the blood; under the most unfavorable circumstances one-fifth of the oxygen will be retained in the blood. Applied directly to nerve and muscle the gas has no influence whatever. Acting through the blood, however, phenomena appear that are indicative primarily of stimulation, but secondarily of paralysis of the nervous system. Thus, there occur at first severe headache, great restlessness, excitement, increased cardiac and respiratory activity, salivation, tremor, twitching, and spasm. Later, mental confusion, exhaustion, drowsiness, and paralysis set in, and even loss of consciousness, labored stertorous breathing, finally complete loss of sensibility, cessation of breathing and of the heart-beat and death. The tem- perature at the beginning exhibits an elevation of perhaps a few tenths of a degree C.; then there follows a decline of about i C. and more. The pulse-beat at first exhibits increased energy, while later the pulse becomes small and frequent. Garland-like constrictions of the vessels, followed later by marked dilatation, with hyperemia of the viscera, accompanied by a fall in the blood-pressure, indicate primary stimulation and secondary paralysis of the vasomotor center. The change in temperature mentioned is to be referred to the same cause. This would also explain the appearance of sugar in the urine sometimes observed in dogs only after abundant feeding of proteid. After the intoxication has ter- minated the excretion of urea is said to be increased, because the albuminates exhibit a greater tendency to disintegration. In cases of poisoning the great hyperemia of the viscera with fluid cherry-red blood and the dilatation of the vessels are conspicuous. Further, there are friability and softening of the brain, marked catarrh of the respiratory organs and granular degeneration of the muscles. Liver, kidneys, and spleen appear hyperemic, large, flabby, in a state partly of granular and partly of fatty degeneration. All of the muscles and viscera exhibit an exquisite cherry-red color. The spots of postmortem lividity are bright red. Poisoned persons if still living should be at once brought into the fresh air. High degrees of intoxication demand transfusion. After recovery from the poisoning, sometimes paralysis, rarely anesthesia, trophic disorders and derange- ment of cerebral activity persist. If mixed with pure oxygen carbon nionoxid acts less rapidly. OTHER HEMOGLOBIN-COMBINATIONS. Nitric-oxid hemoglobin is formed when nitric oxid enters into com- bination with hemoglobin. As this gas in contact with oxygen is at once transformed into nitrous acid, 6o DECOMPOSITION OF HEMOGLOBIN. all of the oxygen must first be removed from the blood and the apparatus, possibly through the passage of hydrogen, in the preparation of nitric-oxid hemoglobin. For this reason it cannot be formed within the body. Nitric-oxid hemoglobin is a still more active chemical combination than carbon-monoxid hemoglobin. It is of a bluish-violet color and in the spectrum it exhibits two absorption-bands, pretty much like those of the two other gas-combinations, but less intense, and not dissolved by reducing substances. The three combinations of hemoglobin with oxygen, carbon monoxid and nitric oxid just considered crystallize like gas-free hemoglobin. They are isomorphous and their solutions are not dichroic. All three gases unite in equal amounts with hemoglobin and they can be ex- pelled in a vacuum. Hydrocyanic acid also forms readily decomposed combinations with hemo- globin. These develop in cases of hydrocyanic-acid poisoning, and they exhibit two bands that are situated somewhat nearer the violet than those of oxyhemo- globin and are slowly obliterated by reducing substances. This hydrocyanic-acid hemoglobin appears to consist of hydrocyanic acid plus oxyhemoglobin. There is, besides, a further combination of hydrocyanic acid with oxygen-free hemo- globin. DECOMPOSITION OF HEMOGLOBIN. Hemoglobin can be decomposed into: (i) iron-containing, pig- mented hematin and (2) albuminoid, colorless globin, containing sul- phur: (a) by addition of all acids, even feeble carbon dioxid in the presence of much water; (b) by strong alkalies; (c) by all agents that coagulate albumin, as well as by heat at a temperature of from 70 to 80 C. ; (d) by ozone. Hematin. C 32 H 32 N 4 FeO 4 represents about 4 per cent, of the hemo- globin in the dog. It is of blackish-blue color in reflected light, brown in transmitted light, insoluble in water, alcohol and ether, but soluble in dilute alkalies and acids, as well as in alcohol containing sulphuric acid or ammonia. It does not occur within the body. Hematin thus developed appears in an amorphous form, although it has also been possible to produce it crystallized in needles and rhombic plates. i. 2. 700 650 600 BO D 550 500 Eb F 450 FIG. 16. The Absorption-spectra of Hematoporphyrin, with the Fraunhofer Lines and a Scale Whose Figures Indicate the Wave-lines of Light in Millionths of a Millimeter. In the decomposition of hemoglobin containing oxygen hematin at once results, oxygen being bound. On the other hand, oxygen-free hemoglobin yields in a similar process of decomposition, at first a forerunner of hematin deficient in oxygen, namely purple-red hemochromogen (C 34 H 36 NFe 4 O 5 ) . This, however, is transformed into hematin in the presence of oxygen by taking up the latter. Hematin therefore represents an oxidization-stage of hemochromogen. The latter IDENTIFICATION OF BLOOD. 6l substance is soluble, with exclusion of oxygen, in dilute alkalies, with the formation of a cherry-red color, and exhibits two absorption-bands, namely, one between D and E, and another and narrower between E and b (Fig. 15, 7). Hemochromogen can be prepared in crystalline form by mixing upon a glass slide one drop of defibrinated blood with one drop of pyridin and covering the whole. The preparation exhibits the absorption-bands and at times also small crystals arranged in the form of stars or sheaves. In the bloody extract of spirit-preparations no longer fresh putrefaction often produces the beautiful red hemochromogen in alkaline solution. Dilute acids in alcoholic solution withdraw the iron from the hemochromogen and there thus results hematoporphyrin C 16 H 18 N 2 O 3 , which is isomeric with bilirubin, and is permanent in the air. This can also be prepared from hematin by means of strong sulphuric acid. It exhibits in acid solution a small absorption- band in the orange and a wider band in the yellowish-green (Fig. 16, i). The spectrum of the same substance in alkaline solutions is shown in Fig. 16, 2. Hematin occurs in solution as (A) Hematin in acid solution. If acetic acid be added to a solution of hemo- globin the latter becomes mahogany-brown in color, as hematin in acid solution develops and is recognized by four absorption-bands in the yellow and the green (Fig. 15, 5)- (B) If this solution be over-saturated with ammonia hematin in alkaline solution develops, exhibiting an absorption-band at the junction between the red and the yellow (Fig. 15, 6). (C) Addition of reducing agents causes disappearance of this band and pro- duces tw r o wide bands in the yellow, due to the reduced hematin thus formed (Fig. 15, 7), and which, according to Hoppe-Seyler, is identical with the hemo- chromogen in alkaline solution. Hematin is prepared in substance by precipitation from a solution of hemin in a weak alkali by addition of a dilute acid. Hemoglobin is transformed into green sulphur-methemoglobin by hydrogen sulphid. This substance also causes the green coloration of putrid portions of the cadaver. Hematin when reduced in alkaline solution with tin and hydrochloric acid yields urobilin. The latter results likewise through the action of hydrogen dioxid on acid hematin. Urobilin is occasionally found in cysts, exudates, and transudates. It forms likewise in sterile blood kept at the temperature of the body. HEMIN (HEMATIN CHLORID); IDENTIFICATION OF BLOOD BY MEANS OF THE HEMIN-TEST. Teichmann prepared in 1853 from the anhydrid of hematin crystals that Hoppe-Seyler recognized as hematin chlorid C 3 2H 30 N 4 O 3 FeHCl. As these may be obtained in characteristic form even from traces of blood they play an important role in forensic medicine. The demonstra- tion of their presence depends upon the fact that the hemoglobin dried and heated with an excess of water-free acetic acid so-called glacial acetic acid, which must burn on a glass rod held in the flame and addition of sodium chlorid yields hemin-crystals (Figs. 17 and 18). These appear in the form of small rhombic plates, columns, or rods, although they probably belong to the monoclinic system. Not rarely they take the form of hemp-seeds or shuttles or paragraph- signs. At times some lie crossed or in tufts. In crystalline form the hemin-crystals of all varieties of blood examined are identical. They are doubly refracting, appearing yellow and glistening under the polarization-microscope, in contrast with their dark surroundings, with marked absorption of the light parallel with the longitudinal axis of the crystal. They are pleochromatic, that is, bluish-black and glisten- 62 IDENTIFICATION OF BLOOD. ing like polished steel in reflected light and mahogany-brown in transmitted light. (1) Preparation from Dry Blood-stains. Several particles of the dry mass are placed upon a glass slide, two or three drops of glacial acetic acid and a minute crystal of sodium chlorid are added, and after the cover-slip has been placed in position heat is carefully applied some distance above a spirit-lamp until a number of small bubbles form. On cooling the crystals will be visible in the preparation (Fig. 1 8). (2) Preparation from, stains upon porous bodies, from which the hemoglobin cannot be scraped. The stained object fabric, wood is extracted with a dilute solution of potassic hydrate and then with water. To both filtered solutions a solution of tannic acid is added, and finally acetic acid until an acid reaction is pro- duced. The resulting precipitate is washed upon a filter, then to a portion thereof upon a glass slide a crystal of sodium chlorid is added, and the whole is dried. Finally, the dried object is treated according to the method just described. (3) Preparation from Liquid Blood. The blood should always have been pre- viously dried slowly and carefully. Then the process is continued as in the first method. 4 -A ^ ^ FIG. i"j. Hemin-crystals: i, from a human being; 2, from a seal; 3, from a calf; 4, from a pig; 5, from a lamb; 6, from a pike; j, from a rabbit. FIG. 18. Hemin-crystals Pre- pared from Blood-stains. (4) Preparation from Dilute Solutions Containing Hemoglobin. To the fluid is added ammonia, next tannic acid and then acetic acid until the reaction is acid. A blackish precipitate of hematin tannate forms rapidly. This is washed upon a filter with distilled water, then dried and heated in the same way as accord- ing to the first method, except that instead of sodium chlorid a crystal of ammo- nium chlorid is added. Not rarely at least small hemin-crystals can be obtained from putrid and lake- colored blood, but under such circumstances the test often fails. Dried with iron- rust, as upon weapons, blood usually no longer yields the reaction. Under such cir- cumstances the matter is, according to Heinrich Rose, scraped away and boiled with dilute potassium-hydrate solution. If blood be present the dissolved hematin forms a fluid that in thin layers presents a bile-green color, but in thick layers a red color. Hemin-crystals have been demonstrated in all classes of vertebrates, as well as in the blood of the earth-worm. From some kinds of blood, as, for instance, that of cattle and of swine, only irregular masses, scarcely recognizable as having crystalline form, at times develop. Hemochromogen , hematoporphyrin, blood rubbed with sand or animal charcoal, addition of certain salts of iron, lead, mercury, and silver and lime prevent the development of the reaction. The crystals of hemin are insoluble in water, alcohol, ether, and chloroform. They are dissolved by concentrated sulphuric acid, with expulsion of hydrochloric acid and the development of a violet-red color. They are dissolved by dilute alkalies. If a solution of hemin-crystals in ammonia is evaporated, then heated to 130 C., next treated with boiling water, which removes the ammonium chlorid formed, HEMATOIDIN. 63 hematoporphyrin results. This is a bluish-black, amorphous powder, becoming brown when rubbed. Its solutions in caustic alkalies are dichroic: that is brownish- red in reflected light, garnet-red in a thick layer with transmitted light and olive- green in a thin layer. The acid solutions are monochromatic brown. For the preparation of hemin-crystals in large amount, it is advisable to heat dry horses' blood with 10 parts of formic acid until bubbles form. If the hemin- crystals are suspended in methyl-alcohol, they dissolve after addition of iodin and application of heat, with the development of a purple color, which becomes brown after addition of bromin and green after the passage of chlorin-gas. All of these exhibit a characteristic appearance in the spectroscope. The glacial acetic acid may be replaced by an alcoholic solution of oxalic or tartaric acid, and the sodium chlorid by salts of iodin or bromin. In the latter event bromin-hematin or iodin-hematin is formed. HEMATOIDIN. An important derivative of hemoglobin is sorrel-colored hematoidin- C3 2 H 36 N 4 O 6 (Fig. 19), which forms in the body from hematin through loss of iron and taking up of water when- ever blood stagnates [outside of the circula- tion and undergoes decomposition, as, for instance, in apoplectic extravasations of blood, in coagulated plugs in blood-vessels (thrombi). It develops regularly in every Graafian follicle from the drop of blood poured out at the menstrual rupture of the follicle. It is free from iron, crystallizes in clinorhombic prisms, and is soluble in FIG. 19. Hematoidin-crystais. chloroform and in warm alkalies. Probably it is identical with the biliary coloring-matter, bilirubin. Pathological. After extensive dissolution of blood in the vessels, as, for instance, after transfusion with foreign blood, hematoidin-crystals have been ob- served in the urine. THE COLORLESS PROTEID OF HEMOGLOBIN. This is designated globin and is closely related to histon. Demonstration. A solution of hemoglobin is made feebly acid with hydro- chloric acid, then one-fifth volume of alcohol is added and the mixture is shaken with ether. The coloring-matter is taken up by the ether and the globin is precipitated by the ammonia. Hydrochloric or nitric acid likewise precipitates the globin, which, however, is redissolved on boiling. Hematin and globin are probably not the sole products of the decomposition of hemoglobin. As hemoglobin-crystals can be decolorized under special conditions, it is most probable that they owe their form to the proteid body. On introducing hemoglobin-crystals with alcohol in a dialyzer surrounded by ether acidulated with sulphuric acid Landois succeeded in decolorizing the crystals. PROTEID BODIES IN THE STROMA. These constitute from 5.10 to 12.24 per cent, of the dry red blood-corpuscles of man, including a globulin participating in fibrin- formation and possible traces of a sugar-forming ferment. Under special conditions it has been observed that the stromata, coherent in masses, form a substance stroma-fibrin resembling fibrin. L. Brunton has found in the nuclei of nucleated red blood-corpuscles a mucin- containing body, Miescher nuclein and Kossel histon united with the latter. 64 REMAINING CONSTITUENTS OF THE RED BLOOD-CORPUSCLES. THE REMAINING CONSTITUENTS OF THE RED BLOOD- CORPUSCLES. The red corpuscles contain further: Lecithin, 1.867 P er cent, in dry erythrocytes; urea, equally divided between erythrocytes and serum; cholesterin, 0.151 per cent.; no fats; lactic acid, in the dog. Lecithin and cholesterin can be obtained by agitating considerable amounts of stroma or isolated blood-corpuscles with ether. If the ether is permitted to evaporate the characteristic globular myelin-forms of lecithin and the crystals of cholesterin will be recognized. Water, 631.63 in the thousand. After abstraction of considerable quantities of blood the amount of water diminishes and the amount of dry substance, as well as the nitrogen of the ery- throcytes, increases. The opposite effect is brought about by infusion of physio- logic salt-solution. Inorganic matters, 7.28 in the thousand, particularly combinations of potassium and phosphoric acid. The phosphoric acid is derived only from consumed lecithin, the sulphuric acid in large part from the hemoglobin consumed in the analysis. Some manganese also is present. Blood-analysis. One thousand parts by weight of horses' blood are made up as follows : 344.18 parts blood-corpuscles, with 128 of solids 383 in the dog, 655.82 parts plasma, with 10 per cent, of solids 617 in the dog. One thousand parts by weight of moist blood-corpuscles are made up as follows : Solids, 367.9 (swine), 400.1 (cattle), 435 (horse), Water, 632.1 (swine), 599.9 (cattle), 565 (horse). The solids include : Hemoglobin, 261 (swine) 280.5 (cattle) Albumin, 86.1 107 Lecithin, cholesterin and other organic matters, . . 12.0 Inorganic matters, 8.9 Including potassium, 5-543 magnesium, 0.158 chlorin, 1.504 phosphoric acid, 2.067 sodium, o 7-5 4.8 0.747 0.017 0.703 2.093 CHEMICAL CONSTITUENTS OF THE LEUKOCYTES. Leukocytes from the plasma of lymphatic glands, as well as pus- corpuscles contain proteids as follows: little albumin, alkali- albuminate and an albuminate resembling myosin and coagulating at 48, two globulins coagulable at 48.5 and 75 C. respectively, together with serum-globulin, peptone and a coagulating ferment, further consider- able nucleins from the nuclei, nucleo-histon, little glycogen, lecithin, cerebrin, cholesterin, fats, protagon, inosite, amidovalerianic acid. Lymphocytes contain 11.5 per cent, of dry matter. In 100 parts by weight of dry pus there are 0.416 earthy phosphates, 0.143 sodium chlorid, 0.606 sodium phosphate, 0.202 potassitmi, in part in the form of monopotassium phosphate. THE BLOOD-PLASMA AND ITS RELATION TO THE SERUM. 65 THE BLOOD-PLASMA AND ITS RELATION TO THE SERUM. The unmodified fluid of the blood is known as plasma. In this, how- ever, there separates, generally soon after escape of the blood from the vessels, a nbrillated substance, namely fibrin. After this separation, the remaining clear fluid, which no longer undergoes coagulation spon- taneously, is known as serum. The plasma is a clear, transparent, somewhat consistent fluid, which in most animals is almost colorless, but in human beings is yellowish and in the horse of citron-yellow color. DEMONSTRATION OF PLASMA. (A) Without admixture. As plasma cooled to a temperature of o C. does not undergo coagulation, the blood flowing from a vein particularly of the horse, which is peculiarly suitable on account of the slowness of coagulation and the rapidity with which sedimentation of the blood-corpuscles takes place-; is received into a narrow, graduated cylinder standing in a cold mixture. In the blood, which remains fluid, the erythrocytes sink to the bottom within a few hours, and the plasma forms above a clear fluid, which can be removed with a cooled pipet. If this is further passed through a filter upon an ice-cold funnel the plasma will also be freed from leukocytes. The amount can be read from the graduated cylinder, but only approximately, because of the presence of plasma between the sedimented corpuscles. If heated, the plasma, in so far as it contains leukocytes, is transformed, through the forma- tion of fibrin, into a tremulous jelly. If, however, it be whipped with a rod the fibrin will be obtained as a stringy mass. Plasma free from leukocytes is not capable of coagulation. If the amount of fibrin in a volume of plasma isolated by whipping (varying between 0.7 and i.o per cent.) and in the same manner the amount in a volume of blood be determined the two results afford a basis for estimating the amount of plasma in the blood. (B) With saline admixture. If the blood flowing from a vein into a graduated cylinder be mixed with agitation with } volume of concentrated solution of sodium sulphate or with a 25 per cent, solution of magnesium sulphate (i volume to 4 volumes of blood), the cells sink to the bottom in a cool place, while the clear supernatant saline plasma, which can be measured, is pipetted off. If the salt be removed from the plasma by means of the dialyzer coagulation takes place. The same result is brought about by dilution with water. FIBRIN: ITS GENERAL PROPERTIES; COAGULATION. Fibrin is the substance that brings about coagulation in shed blood as well as in plasma and likewise in lymph, and in the chyle, by solidification. If the fluids mentioned are placed at rest and left to themselves the fibrin forms innumerable microscopically delicate (Fig. 9) doubly refracting filaments, which hold the blood-cells together like a spider's web, and with the cells form a mass of gelatinous consistency that is known as blood-clot (placenta sanguinis}. At first this is quite diffluent and it is only in the course of from two to fifteen minutes that a number of filaments appear upon the surface that can be removed with a needle, while the interior of the blood-mass is still liquid. In a short time the filaments extend throughout the entire mass. The blood in this stage of coagulation has been designated cruor. Later, in the course of from twelve to fifteen hours, the threads of fibrin contract more and more firmly about the corpuscles, and there then results the more solid, gelatinous, tremulous substance, which can be cut with a knife, and which has expressed a clear fluid, known as blood-serum (serum sanguinis}. The blood-clot takes the shape of the vessel in which 5 66 FIBRIN. the blood has been received. By solution with water of the blood- corpuscles in the broken-up blood-clot the fibrin can be isolated. If the blood-corpuscles sink rapidly in the blood, and if the advent of coagulation be delayed, the upper layer of the blood-clot is only stained yellow on account of the absence of enclosed erythrocytes. This is the rule with horses' blood, but it has been observed in the case of human blood, particularly when inflammation was present in some part of the body. Therefore, this layer has also been designated crusta phlogistica. Such blood is richer in fibrin and therefore coagulates more slowly. The crusta forms also under other conditions, but the cause of its formation is not always clear. Thus it occurs when the specific gravity of the blood-cor- puscles is increased or that of the plasma is diminished, as in cases of hydremia and chlorosis, in consequence of which the corpuscles sink more rapidly, and during pregnancy. The taller and narrower the vessel, the higher is the crusta. It can be readily understood why the blood-clot undergoes greater contraction and appears more contracted in the neighborhood of the unpigmented layer free from corpuscles. If freshly shed blood is whipped with a rod the filaments of fibrin that form collect about the rod, and in this way the fibrin is obtained as a fibrous, grayish-yellow mass from the blood now become defi- brinated. The plasma exhibits analogous phenomena, but it forms only a soft, tremulous jelly, by reason of absence of the resistant blood-corpuscles. The plasma undergoes coagulation only when it contains leukocytes. If these be removed by filtration the plasma is no longer coagulable. Although the fibrin appears voluminous, it constitutes only from o.i to 0.3 per cent, of the mass of the blood. In this connection, it is noteworthy that in two different specimens of the same blood the amount of fibrin may vary considerably. Fibrin is insoluble in water or ether. Alcohol causes it to shrink by dehydration, while hydrochloric acid causes it to swell and assume a vitreous appearance, with transformation into syntonin. In the fresh state fibrin is tough and elastic. If dried, it becomes horn-like, trans- lucent, brittle, and pulverizable. Fresh fibrin is capable of actively decomposing hydrogen dioxid into water and oxygen, just as other fresh animal or vegetable tissue is likewise capable of doing. Boiled or preserved in alcohol it loses this power. In the fresh state it is soluble in from 6 to 8 per cent, solutions of sodium nitrate or sodium sulphate, with the formation of globulin; and in dilute alkalies and ammonia, with the formation of alkali-albuminate. These solutions are not coagu- lated by heat. Also weak solutions of haloid salts (sodium chlorid, ammonium chlorid, potassium iodid, sodium iodid, sodium fluorid, ammonium fluorid) dis- solve fibrin at a temperature of 40, as, for instance, sodium-chlorid solution, from 7 to 20 parts in the thousand, with the production of globulin-bodies and pro- peptone. Fibrin from swine is dissolved by 0.5 per cent, hydrochloric acid and also by malic, oxalic, butyric, acetic, citric, and lactic acids; fibrin from cattle, with greater difficulty. Fibrin exposed to air for a considerable time is not soluble in nitric acid, although it is soluble in neurin. As a result of putrefaction it likewise undergoes solution, with the formation of albumin. Fibrin contains lime, iron, and magnesium. According to Schmiedeberg the fibrin obtained from plasma has the elementary formula C 108 H 162 N 30 SO 34 , while blood-fibrin has the following composition: C 112 H 16 gN 30 SO 35 -f- ^H 2 O. GENERAL PHENOMENA ATTENDING COAGULATION. 67 GENERAL PHENOMENA ATTENDING COAGULATION. Blood does not undergo coagulation in immediate contact with the living and unaltered vessel-wall. Therefore, Bnicke was able to preserve unco- agulated for eight days blood cooled to o in the still beating heart of dead turtles. The blood coagulates rapidly within the dead heart or vessels (but not in the capillaries) or within other channels, as, for instance, the urethra. If blood stagnates in a living vessel, coagulation takes place in the central axis, because it is here not in contact with the living vessel- wall. Coagulation is of the greatest importance in the control of hem- orrhage from injured vessels, which otherwise might terminate fatally. The injured and necrotic tissues of the wound and the vessel-wall lead to the formation of the occluding thrombus by coagulation. If the vessel-wall is altered by pathological processes, as, for instance, rough or inflamed in consequence of a lesion of the intima, coagulation may take place in such a situation even though the circulation be maintained". Coagulation of the blood is prevented or retarded: (a) By addition of alkalies or of ammonia, even in small amounts; further, of concentrated solutions of neutral salts of alkalies and earths alkaline chlorids, also sulphates, phosphates, nitrates, carbonates ; disodium phosphate in 3 per cent, solution, soluble salts of calcium, strontium and barium dissolved in the blood to the extent of 0.5 per cent. Simultaneous addition of sodium chlorid inhibits coagulation in still further degree. Magnesium sulphate i volume of a 28 per cent, solution to 3^ volumes of horses' blood acts most effectively in inhibit- ing coagulation. (b) By precipitation of the calcium by means of oxalic acid. Feeble acids also exert an inhibiting effect. Thus, coagulation ceases after addition of acetic acid to the point of producing an acid reaction. The presence of a large amount of carbon dioxid likewise retards coagulation; therefore, venous blood and also the blood after asphyxiation coagulates more slowly than arte- rial blood. (c) By addition of egg-albumin, sugar-solution, glycerin, soaps or much water. If uncoagulated blood be brought in contact with a layer of already separated fibrin coagulation is retarded. (d) Cold (o C.) retards coagulation for as long as an hour. If blood be permitted to freeze at once, it will still be liquid on thawing, when it undergoes coagulation. Coagulation is retarded also when the shed blood is exposed to high pressure; likewise when it is brought in con- tact with foreign substances to which it does not adhere, as, for instance, anointed substances. (e) The blood of embryo birds does not coagulate at all before the twelfth or fourteenth day on account of the absence of fibrin-forming cells, and that of the hepatic veins but slightly. Blood from the dog passed only through the heart and the lungs does not coagulate for a long time. Blood from the renal vein, also blood cut off from circulation through the liver and intestines, does not coagulate at all. Fetal blood at the moment of birth coagulates early, but slowly, as the amount of fibrin it contains is small. Menstrual blood exhibits a slighter tendency to undergo coagulation if admixed with a considerable amount of alkaline mucus from the genital canal. 68 COAGULATION IS ACCELERATED. (/) In cases of bleeders' disease hemophilia coagulation appears to be want- ing on account of deficiency in the fibrin-generators, in consequence of which wounds of the vessels are not occluded by fibrinous thrombi. The peptic ferment of the pancreas dissolved in glycerin and injected into the blood inhibits its coagu- lation, as does also the diastatic ferment. Schmidt-Mulheim noted the same result after injection of pure peptone into the blood of dogs 0.5 gram to i kilo of dog, and 1.5 of rabbit. This is effective, however, only in the presence of the liver. The buccal secretion of the leech, the poison of vipers and the highly toxic substance in the serum of eels' blood likewise inhibit coagulation. Coagulation is accelerated: (a) By contact with foreign substances to which the blood adheres, as, for instance, threads and needles introduced into the veins. Also the entrance of air-bubbles into the vessels or the passage of other indifferent gases, as, for instance, nitrogen and hydrogen, exerts an accelerating effect. Removed from the vein, the blood coagulates quickly on the walls of the container, on its surface exposed to the air, on the rod with jvhich it is whipped, etc. (6) Many products of the retrogressive metamorphosis of albuminates, including uric acid, glycin, taurin, leucin, tyrosin, guanin, xanthin, hypoxanthin (not urea), as well as the biliary acids, further lecithin, cholin hydrochlorate, protagon, accelerate coagulation through in- creased ferment-formation. Added in excess, however, they exert an inhibiting effect. Solutions of gelatin injected into the veins cause the blood to coagulate almost instantly after escape from the vessels. (c) If hemorrhage takes place rapidly the last amounts of blood coagulate earliest. Fresh fibrin, if permitted to remain for a consider- able time in blood, is again dissolved in part. (d) Heating to a temperature of from 39 to 55 C. accelerates coagulation. In the shed blood of man coagulation begins in the course of three minutes and forty-five seconds; in that of woman after two minutes and thirty seconds. Hunger exerts an accelerating effect. Among vertebrates the blood of birds coagulates almost instantly, that of cold-blooded animals distinctly more slowly, while the blood of mammals occupies an intermediate position. The blood of invertebrates, which mostly is colorless, forms a soft, white fibrinous coagulum. As the process of coagulation involves a change in the aggregate state, heat demonstrable with the thermometer must be set free. In blood removed from a vein the degree of alkalinity diminishes up to the point of completed coagulation, probably from the formation of acid in the blood as a result of decomposition-processes. In the process of coagulation a diminution in the amount of oxygen in the blood has been observed, although this takes place also in blood that has not yet undergone coagulation. There is, likewise, elimination of traces of ammonia. Both processes, however, appear not to stand in causal relation with the formation of fibrin. NATURE OF COAGULATION. Alexander Schmidt discovered in 1861 that coagulation is a fermen- tative process that consists in the transformation of the soluble albumin of the plasma into the solid substances of the fibrin through the activity of an enzyme that is designated fibrin-ferment or thrombin. This pro- teid is nothing but fibrinogen. NATURE OF COAGULATION. 69 The enzymes or hydrolytic ferments behave in common in the organism in such a manner that they break up the bodies upon which they act into two other substances by taking up water. It, therefore, appears probable that as a result of the action of thrombin decomposition of the fibrinogen into fibrin and a lesser amount of a globulin-body that remains liquid and that Hammarsten has designated fibrin- globulin, takes place, with the taking up of water. Demonstration of Fibrinogen C 112 H 168 N 30 SO 35 . Pulverized sodium chlorid is added to lymphatic transudate to the point of saturation. The fluid poured out into the serous sac surrounding the testicle (hydrocele) is especially useful for this purpose. The precipitated fibrinogen is collected upon a filter. This substance is found also in the lymph and in the chyle. Saline plasma also is capable of precipitating fibrinogen by admixture of equal volumes of plasma and a concentrated solution of sodium chlorid. For purposes of purification it may then be dissolved rapidly and repeatedly in a dilute 8 per cent. solution of sodium chlorid and again precipitated by a concentrated solution of sodium chlorid. The fibrinogen contained in the sodium-chlorid solu- tion is precipitated by addition of water and is rapidly changed so that it resembles fibrin. Fibrinogen in saline solution coagulates at a temperature of from 52 to 55 C. Solutions free from salt do not coagulate if quickly brought to the boiling-point. Fibrinogen behaves like globulin. It is soluble in dilute alkalies and it is precipitated from such solutions by the passage of carbon dioxid. It is further soluble in dilute solution of sodium chlorid, while addition of large amounts of sodium chlorid causes its precipitation as a soft, viscous, tough mass. It is dissolved also by dilute hydrochloric acid, although it is soon transformed into a body resembling syntonin (acid albuminate) . In the fresh state it actively decomposes hydrogen dioxid. Its specific rotatory power is 52.2. Demonstration of Fibrin-ferment Thrombin. Blood-serum from cat- tle, which contains a larger amount of ferment than the serum of carnivora, is admixed with twenty times its volume of strong alcohol. The result- ing precipitate is collected upon a filter after the lapse of from two to four weeks. It contains the coagulated albumin and the ferment. It is dried over sulphuric acid and reduced to powder. One dram of this powder is stirred for ten minutes in 65 cu. cm. of water. If the mixture is not filtered, (the ferment, dissolved in water, alone passes through the filter. X Thrombin is formed from a forerunner, a zymogen, which is present within the leukocytes and is designated prothrombin. Both are soluble with greater difficulty in an excess of acetic acid than globulins. Even small amounts of the ferment may cause coagulation of fluids containing fibrinogen and most readily at a temperature of 40 C. Prothrombin is destroyed at a temperature of 65 , thrombin at a temperature between 70 and 75. The amount of ferment formed in the blood is the 'greater the longer the time that has elapsed between the escape and the coagulation of the blood. Blood flowing directly from the vein in alcohol yields no ferment. Coagulation. If the separate solutions (i) of the fibrinogenous sub- stance and (2) of the ferment are admixed fibrin-formation takes place at once. The most favorable temperature for this is that of the body. A temperature of o C. prevents coagulation, while the boiling tem- perature destroys the ferment. The amount of ferment is a matter of indifference. Larger amounts cause more rapid, but not increased, separation of fibrin. For the formation of fibrin the presence of a certain amount of salt in the fluid is requisite one per cent, sodium chlorid. Otherwise the process takes place but slowly and is only partial. The presence of a calcium-salt favors coagulation. If the 70 SOURCE OF THE FIBRINOGENOUS SUBSTANCES. calcium is precipitated by alkali-oxalate this prevents coagulation, although it is true that the presence of a large amount of ferment in the blood is capable of neutralizing the influence of the calcium. Fibrin- ogen and fibrin contain equal amounts of calcium. Probably the action of the calcium bears some relation to -the formation of the fibrin- ferment, for the plasma contains a substance that exerts a marked coagulative effect after addition of calcium-salts. According to Kossel and Lilienfeld the leukonuclein contained in the nuclei of the leukocytes, and the nucleinic acid resulting from its decomposition, accelerate coagulation. If coagulation has taken place in the plasma of the blood, all of the fibrinogenous material in the serum is utilized for the formation of fibrin. On the other hand, fibrin-ferment will still be present in the serum in sufficient amount. Therefore, if blood-serum be added to a fluid containing fibrinogen, as, for instance, hydrocele-fluid, coagulation will at once take place anew. SOURCE OF THE FIBRINOGENOUS SUBSTANCES. Alexander Schmidt has found that both fibrin-factors are formed from the destruction of leukocytes. In the circulating blood of man and of mammals, the fibrinogenous substance is already dissolved in the plasma as a soluble product of the physiologic involution-processes of the white cells. The circulating blood, however, contains a much larger number of leukocytes than was previously believed. As soon as the blood is shed, large numbers of white blood-corpuscles are dissolved according to Alex. Schmidt 71.7 per cent, in the horse. The decom- position-products dissolve in the blood-plasma, and as a result the fibrin- ferment develops, to a certain extent as a cadaveric product, causing the separation of fibrin. Accordingly the fibrin-ferment does not preexist within the uninjured corpuscles. Also the so-called transitional forms between colorless cells and erythrocytes in mammalian blood furnish the fibrin-factors as a result of their destruction, which takes place immediately after escape of the blood ; likewise perhaps also the blood- plates. The ferment develops with the escape of the blood, and its formation reaches the maximum during the process of coagulation itself. The influence of adhesion in favoring coagulation depends upon the fact that as a result the blood-corpuscles are caused to give up a portion of their contents phosphoric acid and alkaline phosphates to the plasma, to combine with salts of calcium and magnesium present principally in the plasma. If the calcium be precipitated from the blood by means of oxalic acid i gram of potassium oxalate to i liter of blood coagulation no longer takes place. If, how- ever, calcium chlorid be again added to this mixture coagulation will result. In the blood of amphibia and birds it is the red blood-corpuscles that after escape undergo destruction in large numbers and furnish the fibrin-forming mate- rials. In the blood of these animals Alex. Schmidt convinced^ himself at the same time that also the fibrinogenous substance was originally a constituent of the blood- corpuscles. It is thus clear that as soon as the fibrin-factors pass into solution in consequence of dissolution of the blood-corpuscles the separation of fibrin must take place through the combination of the two substances. If considerable amounts of leukocytes are introduced into the circulation of an animal they are quickly dissolved in large numbers in the blood, so that even RELATIONS OF THE RED BLOOD-CORPUSCLES. 71 death may take place in consequence of widespread coagulation. If the animal survive immediate death by reason of the moderate extent of coagulation, the blood subsequently will be wholly incoagulable in consequence of the absence of leukocytes. All protoplasmic structures may in combination with plasma set the fibrin-ferment free. The nitrogenous metabolic products of proteids are likewise capable of producing fibrin-ferment in plasma free from cells. These latter active substances can be extracted from the tissues cells of the liver, the spleen, the lymph-glands, red and white blood-corpuscles, frog-muscle by means of alcohol. If after alcoholic extraction the residue of such tissues is extracted with water, this watery extract absolutely inhibits coagulation. The substance thus extracted by water is designated by Alex. Schmidt cytoglobin, which is the forerunner of fibrinogen and also of serum-globulin. In accordance with the preponderance in the plasma of either of the substances capable of extraction with alcohol or cytoglobin, coagu- lation is induced or inhibited respectively. Within the living body the inhibitory action of the cells preponderates, while outside the body the coagulating effect is operative. Those substances, such as the cytoglobin, that inhibit coagulation within the circulation furnish out- side of the body the material for the formation of fibrin. As Alex. Schmidt, after addition of cytoglobin to filtered plasma, induced coagu- lation by addition of extractives in large amount, the amount of fibrin was more than doubled. The blood retains its fluidity in the circulation as long as the amount of cytoglobin exceeds that of the proteid metabolic products of the tissues. The blood may, however, remain fluid also because both of these do not pass over into the plasma. Pathological. From the investigations of Alex. Schmidt in collaboration with his pupils Jakowicki and Birk, it has been shown that even healthy functionating blood contains some fibrin-ferment from the destruction of white blood-corpuscles normally undergoing dissolution, and in greater amount in venous than in arterial blood. Nevertheless, it is always more abundant in shed blood. The fact, how- ever, is particularly noteworthy that the amount of fibrin-ferment in the blood in cases of septic fever may increase to such a degree that spontaneous coagulation- thrombosis takes place and even terminates fatally. After injection of putrid matters leukocytes are dissolved in large number, but the ferment is present rather abundantly also in the blood of febrile patients generally. Also injection of pep- tone, of hemoglobin and in lesser degree of distilled water is followed by dissolution of numerous leukocytes. There are thus true blood-diseases in which the products of the dissolution of the leukocytes accumulate in the blood-plasma. In conse- quence, spontaneous coagulation naturally occurs within the circulatory organs, and as a result death may even be brought about. At least febrile elevation of tempera- ture usually takes place. At the termination of such conditions the coagulability of the blood is naturally diminished. Wooldridge showed that a fibrinogen tissue- fibrinogen occurs in the chyle and in the lymph as a product of the lymphatic glands. In human beings in whom blood-stasis exists in any part of the body, coagulation may take place, with the formation of thrombi, through admixture of lymph, as a certain amount of ferment is already present in the blood. The intestinal mucosa, the skin, and the lungs also appear to produce small amounts of fibrinogen constantly, while the liver and the kidneys constantly destroy it. RELATIONS OF THE RED BLOOD-CORPUSCLES TO FIBRIN- FORMATION. After it had been determined by a number of investigators that also the erythrocytes of birds, of the horse, of the frog, may contribute to the 72 CHEMICAL CONSTITUTION OF BLOOD-PLASMA AND SERUM. production of fibrin, Landois was able in 1874 to follow directly under the microscope the transformation of the stromata of the red blood-cor- puscles of mammals into fibrin-fibers. If a drop of defibrinated rabbit's blood be introduced into frog's serum, without agitation, it will be observed that the erythrocytes attach themselves to one another. They become viscous upon the surface, and on pressure on the cover-slip it will be seen the adhesion can be broken up only with a certain amount of force, the adjoining surfaces of the swollen, globular corpuscles often being drawn out into threads. Even after the process has been in operation for a short time, all of the corpuscles are transformed into globules of lesser diameter and those lying nearest the periphery permit their hemoglobin to escape. The decolorization progresses from the periphery of the drop to the center, and finally only a coherent mass of stroma remains. The substance of the stroma exhibits great tenacity. At first the round contours of the individual blood-corpuscles can still be recognized, but as soon as a current is set up in the surrounding fluid by pressure upon or movement of the cover-glass, the stroma-mass becomes agitated to and fro and the stromata lying close together and adherent to one another become drawn out into delicate filaments and bands, with simultaneous disappearance of the previous contour of the cells. In this way the formation of fibrin-filaments from the stro- mata of the red blood-corpuscles can be followed step by step. Erythro- cytes from human beings and from animals undergoing dissolution in the serum of different animals often exhibit the same phenomena. Stroma-fibrin can be prepared also in the following simple manner: A one per cent, solution of sodium chlorid is shaken in a reagent-glass with ether and a few drops of defibrinated blood. The mixture soon becomes lake-colored. Put aside, the ether, which rises to the tpp, carries with it the filamentous stroma- fibrin to the surface of the fluid. Stroma-fibrin and Plasma-fibrin. Landois has designated stroma- fibrin that which arises directly from the stroma of the erythrocytes. On the other hand, the fibrin that is produced through the combination of the fibrin-factors dissolved in the coagulating fluid plasma is plasma- fibrin, or ordinary fibrin. Both designations are fully justified, if only to indicate the mode of origin of the fibrinous mass. Substances that cause rapid dissolution of the erythrocytes bring about extensive coagulation, as, for instance, injection of bile or salts of the biliary acids, or of lake-colored blood into the veins. The effective agent under these circumstances is the stroma, through the development of the ferment, and in lesser degree the hemoglobin. As foreign blood after injection often undergoes rapid disintegration in the blood-stream of the recipient, extensive coagulation is often observed under such circumstances, while at the same time the individual smaller vessels are often occluded by plugs of stroma-fibrin . CHEMICAL CONSTITUTION OF THE BLOOD-PLASMA AND THE SERUM. The proteids constitute about 8 or 10 per cent, of the plasma. Of these only about 0.2 per cent, are bodies producing fibrin. If these be eliminated through the process of coagulation, the plasma is trans- formed into serum. The specific gravity of human serum is between 1027 and 1029. The blood-plasma contains, besides, the following proteids: SERUM-ALBUMIN, SERUM-GLOBULIN. 73 (a) Serum-albumin C 78 H 120 N 20 SO 24 from 3 to 4 Per Cent. Its per- centage-composition is C 53.1, H 7.1, N 15.9, S 1.9, O 22, Ash 0.22. Its coagulation-temperature is from 51 to 53 C.; its specific rotatory power 61. In the horse and the rabbit it crystallizes in hexagonal prisms, with a pyramid upon one side. The crystals are doubly refracting, up to i cm. in length, and are coagulable by heat. It is a remarkable fact that serum-albumin is absent from the blood of starving snakes and it makes its appearance only after feeding. (b) Serum-globulin also known as fibrino plastic substance or para- globulin and also as serum-casein from 2 to 4 per cent. If magne- sium sulphate in substance is added to serum to the point of saturation, serum-globulin is precipitated at a temperature of 35 C. It is washed upon a filter with concentrated solution of magnesium sulphate. It is soluble in a 10 per cent, solution of sodium chlorid, and coagulates at a temperature of from 69 to 75 C. Its specific rotatory power is 47.8, and its formula is C 117 H 174 N 3 oSO 38 . After precipitation of the serum-globulin from the serum by means of mag- nesium sulphate the serum-albumin is precipitated by further saturation with so- dium sulphate. Neutral ammonium sulphate, added to the point of saturation, precipitates all of the proteids of the blood-serum, arid also those of egg- albumin and of milk ; further, propeptone, but not peptones. Globulin can be precipitated also by dialysis of the serum, as it is insoluble in solutions free from salt. During hunger the amount of globulin increases, while that of albumin dimin- ishes. After abstraction of blood the amount of globulin in the blood increases. Paraglobulin occurs also in erythrocytes, as well as in the fluids of the connective tissue and the cornea. According to von Jaksch, 100 cu. cm. of blood contain 22.62 grams of albumin, while an equal amount of serum contains more than 8 grams. The latter figure varies under pathological conditions. Fats from o.i to 0.2 Per Cent. Neutral fats stearin, palmitin, olein occur in the form of minute microscopic droplets, whose presence often renders the serum of a milky turbidity after abundant ingestion of fat and also of milk. They are more abundant during hunger and in drunkards. There occur, besides, soaps, lecithin, and its decompo- sition-product, glycerin-phosphoric acid, and cholesterin. Hiirthle found cholesterin oleate and palmitate 0.17 per cent. According to Hanriot a ferment, known as lipase, occurs in blood and which breaks up neutral fat into glycerin and fatty acids. Lipase is found also in the pancreas and in the liver, and traces also in some other parts of the body. A certain amount of grape-sugar from o.i to 0.15 per cent., some- what more in the blood of the hepatic veins, derived from the liver and the muscles and increased after loss of blood ; some glycogen increased in cases of diabetes; a trace of animal gum, a reducing substance, insusceptible of fermentation and soluble in ether, jecorin, which is a combination of dextrose and lecithin ; a dextrose-forming diastatic fer- ment, inactive at a temperature of 65 C. For a discussion of the sugar- destroying power of the blood reference may be made to the section on the liver. The amount of sugar in the blood is increased by absorption of sugar from the intestinal tract, and in greatest degree in the blood of the portal and hepatic veins. It is increased also in arterial blood, although here it is rapidly changed. For purposes of demonstration blood is coagulated by boiling after addition of sodium sulphate, and the amount of sugar in the expressed fluid is determined with the aid of Fehling's solution. Pavy digested the blood thrice successively 74 ABSORPTION OF GASES BY SOLID BODIES AND FLUIDS. with six times its volume of alcohol, then boiled and expressed the product. The extract, which is evaporated, contains all of the sugar. Kreatin, urea during hunger 0.035 per cent., in the stage of maxi- mum formation 0.153 per cent. ; at times succinic acid, hippuric acid, and uric acid (i : 6000 in gouty individuals); guanin (? carbamic acid); in the blood after death also sarcolactic acid. All of these are present in exceedingly small amount. Inorganic matters 0.85 per cent.; principally sodium-combina- tions. The amount of salts is increased by a meat-diet, while it is dimin- ished by a vegetable diet. Ammonium is present in the proportion of i mg. to 100 cu. cm., and three or four times as abundantly in the blood of the portal vein. Human blood-serum contains the following salts : Sodium chlorid, 4.92 in 1000. Sodium sulphate, 0.44 Sodium carbonate, 0.21 " Sodium phosphate, o^S " Calcium phosphate, 1 , ( Magnesium phosphate, / -73 The alkaline reaction of. the serum depends principally upon the sodium car- bonate present. It is only half that of the blood. The serum of blood containing carbon dioxid in large amount exhibits a more pronounced alkaline reaction and the amount of chlorin contained is diminished. This is dependent upon the fact that hydrochloric acid and water enter the blood- corpuscles, while the alkali remains behind. If salts in considerable amount are introduced into the blood, the larger amount disappears in the course of a few minutes, diffusing principally into the tissues. Gradually they are eliminated from the body through the kidneys. The same statement is applicable to sugar and peptone. Water about 90 per cent. Yellowish pigments. One pigment can be separated by agitation with methyl-alcohol. It exhibits two absorption-bands of lipochrome, like lutein. Hydrobilirubin was found by Maly, and choletelin by MacMunn. Blood, and also blood-serum free from cells, as well as lymph, possess bacter- icidal properties, which are augmented by increase in the alkalinity, but, on the other hand, disappear on addition of water, on heating to a temperature of 55 C., on exposure to diffuse daylight, and likewise if mineral matters are removed by dialysis. Egg-albumin and fresh milk exhibit the same properties. The corpuscle- destroying globulicidal action of fresh serum is peculiar to the latter, in con- junction with its bactericidal effect after bacterial invasion. Both properties are due to certain proteid bodies known as alexins. The serum of an individual rendered immure by inoculation to any infectious disease exerts an antitoxic effect against the poison of the corresponding infectious agent, and it can there- fore be employed against the latter for curative purposes. Large numbers of microbes may gain entrance into the blood-stream during the death-agony. The serum of individuals suffering from typhoid fever contains a substance of diagnostic importance, designated agglutinin, which causes agglutination of typhoid bacilli in cultures. THE GASES OF THE BLOOD. ABSORPTION OF GASES BY SOLID BODIES AND BY FLUIDS. Between the particles of solid, porous bodies and gaseous substances there exists a marked attraction of such a character that the gases are attracted by the solid bodies and condensed within their pores; that is, the gases are absorbed by the solid bodies. Thus, for instance, one volume of boxwood charcoal, at a tern- DIFFUSION OF GASES. 75 perature of 12 C. and a pressure of 760 mm. of mercury, absorbs 35 volumes of carbon dioxid, 9.4 volumes of oxygen, 7.5 volumes of nitrogen, 1.5 volumes of hydrogen. The absorption of the gases is invariably attended with the generation of heat, which is in proportion to the energy with which absorption takes place. Non-porous bodies are in an analogous manner surrounded intimately upon their surface by a layer of condensed gas. Fluids are in like manner capable of taking up or absorbing gases. In this connection it has been learned that a given amount of fluid at different pressures nevertheless always absorbs an equal volume of gas. Whether the pressure be great or small, the volume of gas absorbed is always the same. It is, however, known, according to the law of Boyle-Mariotte, governing the compression of gases, that with twice, thrice or greater amounts of pressure, twice, thrice or greater amounts of gas by weight are contained within an equal volume of gas. From this there is formulated the law that while at varying pressures the volume of gas absorbed remains the same, the amount of gas by weight contained within the same volume is directly proportional to the amount' of pressure. If, therefore, the pressure is zero the amount of the absorbed gas must likewise be zero; whence it follows that fluids under the air-pump in a vacuum may be deprived of their absorbed gases. The coefficient o absorption represents that volume of gas that is absorbed by i volume-unit of a fluid at a given pressure and temperature. From what has been said with regard to the volume of absorbed gases the coefficient of ab- sorption must be wholly independent of the pressure. The temperature has an important influence upon the coefficient of absorption. When the temperature is low the coefficient is highest, declining at a higher tem- perature and becoming zero when the fluid boils. From this it follows that ab- sorbed gases can also be expelled from fluids by heating the latter to the boiling- point. The coefficient of absorption increases, however, for various fluids and gases with increasing temperature in a peculiar, and by no means uniform, manner, which must be determined empirically for each. At the temperature of the body the coefficient of absorption of carbon dioxid is 0.5283, of nitrogen 0.0119, of oxy- gen, at a pressure of 699 mm., 0.0231. DIFFUSION OF GASES; ABSORPTION OF GASEOUS MIXTURES. Gases that do not enter into chemical combination with one another are capable of forming a uniform mixture. If, for instance, the necks of two flasks are connected of which the lower contains carbon dioxid and the upper, placed vertically and inverted above the other, contains hydrogen, both gases combine, independently of differences in specific gravity, within each flask so as to form identical mixtures. This phenomenon is known as the diffusion of gases. If a porous membrane be previously interposed between the two gases the interchange of gases takes place just the same. Nevertheless different gases pass through the interstices of the membrane with unequal rapidity in the same way as in the case of fluids in the process of endosmosis, so that at first a larger amount of gas will be present upon the one side than upon the other. According to Graham the rapidity with which gases pass through the interstices is inversely as the square root of their specific gravity, but according to Bunsen, not exactly so. Gases mutually exert no pressure upon one another. Therefore a gas escapes from a space containing another gas as from a vacuum. If, accordingly, the sur- face of a fluid in which a gas is absorbed be placed in communication with a large amount of another gas, the absorbed gas passes over into the other gas. Therefore, absorbed gases can be removed if the fluids containing them are treated with other gases by agitation or by passing them through. If two or more gases in mixture lie over a fluid within a closed space the separate gases will be absorbed, and according to weight in proportion to the pressure to which each gas would be exposed if it were alone present in the space. This pressure is known as partial pressure. The amount of gas absorbed from mixtures is therefore proportionate to the partial pressure. The partial pressure of a gas in a space partially filled by a fluid is at the same time an expression of the ten- sion of the absorbed gas in this fluid. The air contains 0.2096 volume of oxygen and 0.7904 volume of nitrogen. If, therefore, one volume of air is present at a pressure P over water, the partial pressure under which oxygen is absorbed is 0.2096 x P, and that for nitrogen equals 0.7904 x P. At a temperature of o C. and at 760 mm. pressure i volume 76 SEPARATION OF THE GASES OF THE BLOOD. of water absorbs 0.02477 volume of air, consisting of 0.00862 volume of oxygen and 0.01615 volume of the nitrogen. It accordingly contains 34 per cent, of oxygen and 66 per cent, of nitrogen. Water, therefore, absorbs from the atmos- pheric air an amount of gas that is by percentage richer in oxygen than the air itself. SEPARATION OF THE GASES OF THE BLOOD. The expulsion of the gases of the blood and their collection for chemical .analysis are effected by means of the mercurial air-pump. The Pfluger pump for the extraction of gases is illustrated diagrammatically in Fig. 20. It consists of a blood-receptacle (A), a glass flask with a capacity of from 250 to 300 cu. cm., drawn out above and below into tubes, each of which can be closed by means of a stop-cock (a b). The cock b is an ordinary stop-cock, while the cock a has a channel passing through its longitudinal axis and opening at x in such a manner that in accordance with its adjustment it leads either into the receptacle (position x a) or downward through the lower tube (position x' a') . This receptacle is first completely deprived of air by application to a mercurial air-pump and is then weighed. Next, the extremity x' is tied in an artery or a vein of an animal and by placing the lower cock in the position x a the blood is permitted to flow into the receptacle. When the desired amount has been col- lected the lower cock is again placed in the position x' a', the exterior is carefully cleaned and the receptacle is weighed in order to determine the weight of the blood collected. The second portion of the apparatus is the froth-vessel chamber (B) , likewise drawn out above and below into tubes, which can be closed by means of the cocks c and d. The purpose of the froth-chamber is to take up the froth formed in consequence of the active escape of the gases from the blood. Below, the froth- chamber is connected with the receptacle by means of a ground-glass tube and above likewise through a well-fitting tube with the drying apparatus (G). This consists of a U-shaped tube expanded below into a glass bulb. The latter is half filled with sulphuric acid, while each arm contains bits of pumice-stone saturated with sulphuric acid. In passing through this apparatus, which likewise may be closed by means of the two stop-cocks e and f, the gases of the blood yield up their watery vapor to the sulphuric acid, so that they may be conveyed through the cock f in a perfectly dry state. The short tube D is similarly connected with the prolongation from f by means of a properly ground surface, and it is provided with a small manometer from which the degree of vacuum can be read. The tube D communicates with the pump -apparatus proper. This consists of two large glass flasks, E and F, terminating above and below in open tubes, the lower of which, Z and w, are connected by means of a rubber tube G. Both flasks and the tube are filled with mercury to about half the height of the flasks. The flask E is secured, while the flask F can be raised and lowered by means of a pulley-apparatus attached to a stand. When F is raised E becomes filled, and when F is lowered E is emptied. The upper extremity of E divides into two tubes, g and H, of which g is connected with D. The tube h, passing upward, becomes greatly narrowed and further on is so curved that its free extremity, i, dips into a basin containing mercury, v, with its opening below the tube for the reception of the gases, J (eudiometer- tube) completely filled with mercury. At the junction of g and H there is a cock with a double channel, which in the position H connects the flask E with A B G D, and in the position K closes A B G D and connects the flask E with the tube J. In the first place, B G D is completely exhausted of air by the following steps: The stop-cock is placed in the position K; and F is raised until globules of mercury pass from the free tube i, which is as yet not placed below J, into the basin. Then the stop-cock is placed in the position H, when F is depressed. Next, the cock is placed again in the position K, and so on, until the manometer y indicates that evacuation has taken place. Now, J is placed over i. If the cocks c and b are opened, so that the receptacle A communicates with the remainder of the apparatus, the gases of the blood pass actively into B, with the generation of foam, and through G, dried, to E. The depression of F brings them principally into E. Finally, the cock is placed in the position K, while F is raised, and the gases are conveyed to J above the mercury. Repeated depression and elevation of G with appropriate adjustment of the cock will finally bring all of the gases into J. The removal of the gases from the blood is materially facilitated by placing the recipient A in a vessel containing water at a temperature of 60 C. It is QUANTITATIVE ESTIMATION OF GASES OF THE BLOOD. 77 advisable in the analysis of the gases of the blood to evacuate at once the blood discharged from the vein into the receptacle, because on standing outside of the body the amount of oxygen undergoes a diminution. Mayow, in 1670, was the first to observe gases arise from the blood in a vacuum, and Priestley demonstrated the presence of oxygen and Davy that of carbon FIG. 20. Diagrammatic Representation of Pfliiger's Pump for the Extraction of the Gases of the Blood. dioxid. Magnus, in 1857, investigated the percentage-composition of the gases of the blood. The important recent investigations have been made principally by Loth. Meyer, in 1837, and by C. Ludwig and Pfliiger and their pupils. QUANTITATIVE ESTIMATION OF THE GASES OF THE BLOOD. The evacuated gases consist of oxygen, carbon dioxid, and nitrogen. The gases of the blood obtained with the aid of the pump will be found in the eudiometer-tube (Fig. 20, J), an accurately graduated glass tube in w r hose 78 THE GASES OF THE BLOOD. closed upper portion two platinum wires, p n, are soldered. The eudiometer is closed below by mercury. Estimation of the Carbon Dioxid. A globule of potassic hydrate fused to a platinum wire and moistened on its surface is brought from below through the mercury into the gaseous mixture. The carbon dioxid unites with the potassium hydrate to form potassium carbonate. After remaining in place for a considerable period of time, the globule is removed in the same way. The diminution in the volume of the gases indicates the volume of the carbon dioxid removed. Estimation of the Oxygen. In the same way as in estimating the carbon dioxid a globule of phosphorus is introduced into the eudiometer-tube by means of a platinum wire and which takes up the oxygen for the formation of phosphoric acid; or a dry globule of coke or papier mache saturated with a solution of pyro- gallic acid in potassic hydrate, which eagerly takes up oxygen. After removal of the globule the diminution in volume of the gases indicates the amount of oxygen. The oxygen can be determined most accurately and most rapidly, according to Volta and Bunsen, by explosion in the eudiometer. An abundance of hydro- gen, whose volume is carefully determined, is introduced into the eudiometer- tube. Then an electric spark is made to pass through the tube between the wires p and n. The oxygen and the hydrogen combine to form water. In consequence a reduction in the volume takes place in the eudiometer, of which a third represents the oxygen required for the formation of the water. Estimation of the Nitrogen. If the carbon dioxid and the oxygen are removed from the gas-container according to the methods described the remainder consists of nitrogen. SPECIAL FACTS CONCERNING THE GASES OF THE BLOOD. Oxygen is present in arterial blood from the dog on an average to the amount of 18.3 volumes per cent., at a temperature of o C. and i meter of mercurial pressure. Arterial blood is saturated, according to Pfltiger, to T 9 Q-, according to Hiifner that of the dog to |i> with oxygen. By means of thorough artificial respiration in animals in the state of apnea or by active agitation of the blood with air the amount of oxygen can be brought up to 23 volumes per cent. Venous blood con- tains on the average 8.15 volumes per cent, less of oxygen than arterial blood, although the amount of oxygen varies widely in accordance with the tissues and the circulatory conditions. Sczelkow found 6 volumes per cent, in the blood of resting muscles. Only traces are present in the blood after asphyxiation. In the more highly colored blood of active glands, such as the salivary glands and the kidneys, oxygen is undoubtedly present in larger amount than in ordinary, darker venous blood. The oxygen occurs in the blood as follows: (a) From o.i to 0.2 volume per cent, are in a state of simple absorp- tion in the plasma thus only a minimal portion, not exceeding that which distilled water at the temperature of the blood and at the partial pressure of oxygen in the air of the lungs would take up. (b) Almost all of the oxygen of the blood is combined chemically, and with the hemoglobin of the erythrocytes, with which it forms oxy- hemoglobin ; it is therefore not subject to the laws of absorption. The total amount of blood acts with regard to the chemical absorption of oxygen like a gas-free solution of hemoglobin, except that the absorp- tion of oxygen by the blood takes place more rapidly than by a solution of hemoglobin. At a temperature of o and at moderate atmospheric pressure 760 mm. of mercury i gram of hemoglobin takes up from 1.6 to 1.8 cu. cm. of oxygen according to Hiifner 1.592 cu. cm. OZONE IX THE BLOOD. 79 The absorption of oxygen on the part of the blood is thus independent of the pressure. This is seen also in shed blood, which, on the one hand, permits more abundant escape of the chemically combined oxygen only when the pressure becomes reduced to about 30 mm. of mercury (at a temperature of 12 C. with increasing temperature at a lower pressure), while, on the other hand, it takes up only little more oxygen even if the air-pressure be enormously high, up to six atmospheres. The same phenomenon is exhibited by the blood in the living body, for both on the highest mountains as well "as in the deepest valleys it takes up oxygen in accordance with its requirements. Also, animals breathing in a closed space are capable of abstracting the oxygen from the surrounding air down to the minutest trace. In spite of the chemical combination existing between the hemo- globin and the oxygen, the total amount of oxygen in the blood can be driven out by those agents that set free absorbed gases: (a) by evacuation ; (b) by boiling ; (c) by the passage of the gases ; because the chemical union of oxyhemoglobin is so feeble that it is broken up by the physical procedures named. Among chemical agents, reducing substances, such as ammonium sulphid, hydrogen sulphid, solutions of alkaline subsalts, iron filings, etc., extract oxygen from the blood. The amount of iron present in the blood 0.55 in 1000 parts is in direct proportion to the amount of hemoglobin, this to the number of erythrocytes and the latter in turn approximately to the specific gravity of the blood. The amount of oxygen taken up by the blood has been shown to be almost proportional to the specific gravity of the blood. It is, therefore, also proportional to the amount of iron in the blood. According to Hoppe-Seyler i atom of iron may combine with 2 atoms of oxygen in the blood. According to Bohr the combination is said to be an unstable one. The latter investigator even differentiates, several varieties of com- bination between oxygen and hemoglobin, in accordance with the amount of bound oxygen namely, 0.4 or 0:75 or 3 cu. cm. of oxygen, at a temperature of 15 C. and an oxygen-pressure of 150 mm. to i gram of hemoglobin. Also carbon monoxid is believed by Bohr to be taken up in varying amounts in an analogous manner. Immediately after escape of the blood a slight loss of oxygen takes place as a physiological manifestation of tissue-respiration within the living blood. After having been outside the circulation for some time the amount of oxygen is found to undergo progressive diminution, and after a long time and at a high temperature the oxygen may have wholly disappeared from the blood. This latter loss of oxygen is due to decomposition within the shed blood, in consequence of which reducing substances form and these take up the oxygen. Not all varieties of blood act .in this connection with equal energy in the destruction of oxygen. The venous blood of active muscles acts most energetically, while the blood of the hepatic veins is scarcely at all active. In place of the oxygen that has dis- appeared carbon dioxid makes its appearance in the blood, whose color becomes dark. At times the amount of carbon dioxid is even larger than that of the oxygen destroyed. AS TO THE PRESENCE OF OZONE IN THE BLOOD. On account of the varied and in part active oxidation-processes that take place through the intermediation of the blood, the question has been raised whether the oxygen in the blood may not be present in the form of ozone (O 3 ). However, neither in the blood itself nor yet in the gases evacuated from the blood can ozone be found. Nevertheless, the red blood-corpuscles, as well as the hemoglobin, have a definite relation to ozone. The hemoglobin acts as a conveyer of ozone, that is, it is capable of taking away the ozone from other bodies, and conveying it to other oxi Hzable substances. 80 CARBON DIOXID AND NITROGEN IN THE BLOOD. Oil of turpentine that has been exposed to the air for a considerable time always contains ozone. Among reagents for ozone are potassium-iodid paste, which becomes blue, as the ozone releases the combination of iodin and potassium, and the iodin causes the starch-paste to become blue; further, freshly prepared solution of guaiac-resin in alcohol, which also is made blue by ozone. A solution of guaiac is dropped in water, the resin forming a milky precipitate, and oil of turpentine is added. At first no reaction occurs, but if blood or hemoglobin be added, with agitation, a bluish discoloration appears, that is, the blood takes the ozone from the oil of turpentine and conveys it to the guaiac-resin. It has been stated that hemoglobin acts as an ozone-producer; that is, it is capable of generating ozone from the inactive oxygen of the air with which it comes in contact. For this reason, red blood-corpuscles alone also cause guaiac to become blue. The reaction is most successful if the solution of guaiac is per- mitted to dry upon blotting-paper and then several drops of blood diluted from 5 to 10 times are added. That under these circumstances the condition is one of stimulation of the surrounding oxygen through the hemoglobin, is shown by the observation that even red blood-corpuscles containing carbon monoxid bring about the blue coloration, naturally not when the extraneous oxygen of the air is excluded. According to Pfluger these reactions take place only with decompo- sition of the hemoglobin, and for this reason it is believed that the blood-corpus- cles as such do not act as producers of ozone." Also hydrogen sulphid is decomposed by the blood, as by ozone itself, into sulphur and water. Hydrogen dioxid likewise is decomposed by the blood into oxygen and water. This can be prevented by the addition of a small amount of hydrocyanic acid. Crystallized hemoglobin does not bring this result about, and hydrogen dioxid can be cautiously injected into the veins of animals. From this it would appear that unaltered hemoglobin has no ozone-producing effect. There are three varieties of oxygen: (i) Ordinary or inactive oxygen (O 2 ) , as, for instance, that of atmospheric air. (2) Active or nascent oxygen (O), which can never occur in the free state, but which on its development at once enters into chemical combination as a most powerful oxidizing agent. This is capable of oxidizing water into hydrogen dioxid, the nitrogen of the air into nitrous and nitric acids, and also carbon monoxid into carbon dioxid which ozone is not capable of doing. This gas certainly plays an important role in the organism. (3) Ozone (O 3 ) forms through the breaking up of certain molecules of ordinary oxygen (O 2 ) into two atoms each (O), and union of each of these atoms with an undecomposed molecule of oxygen. Ozone is a form of oxygen compressed to two-thirds of its volume. CARBON DIOXID AND NITROGEN IN THE BLOOD. Carbon dioxid is present in arterial blood in from 34 to 38 volumes per cent., at a temperature of o C. and a pressure of i meter; in venous blood on the average in 9.2 volumes per cent, more than in arterial blood, varying greatly in accordance with the situation and the circulatory conditions. The total amount of carbon dioxid in the blood does not equal even one-half of that which the blood would actually be capable of taking up. Thus, the blood after asphyxi- ation may contain as much as 52.6 volumes per cent. The amount of carbon dioxid in the lymph after asphyxiation is less than that in the blood. The carbon dioxid can be completely pumped out of the total volume of blood without the formation of acids in the process of evac- uation in consequence of decomposition of the constituents of the blood which might take part in driving out the carbon dioxid. The Carbon Dioxid of the Plasma or the Serum. (a) This is absorbed in smallest part simply by the blood-plasma. (b) The largest part of the carbon dioxid is combined chemically with the blood-plasma, independently of the pressure. This combi- nation may take place in the following manner: i. A portion of the carbon dioxid is loosely combined with sodium carbonate, forming sodium bicarbonate, one equivalent of carbon dioxid being taken up by INDIVIDUAL CONSTITUENTS OF THE BLOOD. 8l the simple carbonate: CO 3 Na 2 -f CO 2 4- H 2 O =2CO 3 NaH. In this way considerable amounts of carbon dioxid may be bound. As the sodium bicarbonate releases the carbon dioxid but slowly in a vacuum, while blood releases it with violence, it must be borne in mind that perhaps sodium combined with a proteid (serum- globulin alkali) contains the carbon dioxid in a complex combination, from which it readily separates in a vacuum. 2. A minimal portion of the carbon dioxid of the plasma might be combined chemically with neutral sodium phosphate: One equivalent of this salt may combine with one equivalent of carbon dioxid, so that acid sodium phosphate and acid sodium carbonate result: PO 4 Na 2 H + CO 2 + H 2 O = PO 4 NaH 2 + CO 3 XaH. In the process of evacuation the carbon dioxid escapes, with the formation of neutral sodium phosphate. As, however, the sodium phosphate formed in blood- ash has resulted almost wholly from the combustion of lecithin and nuclein, only the small amount of this salt already present in the plasma can be taken into consideration. The Carbon Dioxid in the Blood-corpuscles. The erythrocytes also contain carbon dioxid in loose chemical com- bination. In denbrinated human blood 31.12 volumes per cent, of carbon dioxid have been found in the serum, and only 4.5 in the blood- corpuscles. The combination of the carbon dioxid is effected in part, through the hemoglobin, therefore through the formation of carbohem- oglobin, in part from the globulin-alkali combinations of the erythro- cytes. The leukocytes also combine with carbon dioxid in accordance with the character of the constituents of the serum, and in about the proportion of from T ^ to \ of the absorptive power of the serum. According to Bohr there are three varieties of carbon-dioxid combination with hemoglobin, which, while closely resembling one another, take up different amounts of carbon dioxid namely 1.5, 3 and 6 cu. cm. of carbon dioxid respec- tively to i gram of hemoglobin, at the same partial pressure for the carbon dioxid and at the same temperature. Spectroscopically, carbon-dioxid hemoglobin re- sembles reduced hemoglobin, except that its absorption-band lies somewhat nearer the violet, and it absorbs more light in the green. Hemoglobin can take up oxy- gen and carbon dioxid at the same time, and each independently of the other. Therefore it is probable that oxygen and carbon dioxid unite with different con- stituents of the hemoglobin. The amount of carbon dioxid in the blood is diminished by alcoholic intoxica- tion, while it is increased by inhalation of ether, w r hich reduces the amount of oxygen. Subcutaneous injection of morphin or chloral diminishes the amount of oxygen. After administration of iodin, mercury, sodium oxalate and nitrate there is a reduction in the amount of carbon dioxid in arterial blood. The same result is brought about in the blood of animals by injection of peptone into the veins, and also in the febrile state on account of the lessened alkalinity of the blood. Nitrogen is present in the blood in the proportion of from 1.4 to 1.6 volumes per cent, in a state of simple absorption. For every 100 parts of nitrogen there are 2.1 parts of argon, which, however, is present only in the plasma. The blood contains more nitrogen when the number of erythrocytes is larger than when the number is smaller and when the blood is lake-colored. Jolyet and Sigalas believe, therefore, that the erythrocytes, like solid bodies, absorb nitrogen at their surface. On standing outside the body,, the blood yields small amounts of ammonia, particularly with access of oxygen and application of heat, perhaps in consequence of decomposition of an as yet unknown ammonium-salt. ESTIMATION OF THE INDIVIDUAL CONSTITUENTS OF THE BLOOD. Estimation of the Water and of All of the Solid Constituents of the Total Blood or of the Serum. About 5 grams of serum or defibrinated blood are evaporated in a crucible of known weight over a water-bath and dried in a drying chamber 6 82 ARTERIAL AND VENOUS BLOOD. at a temperature of no C. The loss of weight represents the amount of water that was present. The dry residue is determined by subtracting the weight of the crucible. For clinical purposes Stintzing weighs a few drops of blood in a Hight, covered glass dish. This he dries for six hours at a temperature of 65 C. -raaid weighs the residue. The amount of water was found to be in men 78.3, Tin women 79.8. The dry residue corresponds approximately with the amount of rproteids contained in the blood and it declines in the presence of anemia. Estimation of the Fibrin. A measured volume of blood is whipped with a rod. After complete separation, all of the fibrin is collected upon a satin filter and washed with water; then placed in a dish and again washed with water, alcohol and ether; next dried in a drying chamber at a temperature of 110 C., and finally weighed. Kossler and Pfeiffer estimate the amount of nitrogen in the serum and in the plasma according to the method of Kjeldahl; the difference represents the amount of nitrogen in the fibrin. The fibrin in 100 cu. cm. of plasma contains 39 mg. of nitrogen (from 30.8 to 45). The fibrin is increased in cases of pneumonia, acute articular rheumatism, erysipelas, scarlet fever, peritonitis (to between 80 and 152 mg.). Estimation of the Fats (Ethereal Extract} in the Serum or the Total Blood. About 15 grams of defibrinated blood or serum are dried in a dish at first over a water-bath, then in a drying chamber at a temperature of 120 O., rubbed up, and placed in a flask with ether, which is repeatedly renewed. The method just described is followed in preparing an alcoholic extract from the total blood or the serum. Estimation of the Inorganic Salts in the Total Blood or Serum. About 25 grams are dried in a weighed platinum crucible and then reduced to ash over a free flame at red heat. The amount of ash is determined by weighing. If this ash be repeatedly extracted with hot water, and the latter be entirely evaporated in a weighed dish, the weight of the salts soluble in water will be obtained. Estimation of the Total Proteids in Blood or Serum. E. Salkowski precipitates all albuminates by means of sodium chlorid and acetic acid. For this purpose he places 20 grams of pulverized sodium chlorid and 50 cu. cm. of blood in a dry flask and adds 100 cu. cm. of a mixture of 7 volumes of concentrated solution of sodium chlorid and i volume of acetic acid, agitating for 20 minutes and filtering- The filter is dried and weighed. V. Jaksch takes i gram of blood from a cupping glass, estimates the amount of nitrogen contained by the method of Kjeldahl, and multiplies the result obtained by 6.25. Estimation of the Proteids of the Blood-corpuscles. If the proteids contained in one part by weight of the total blood and also of the serum have been deter- mined, and if the amount obtained for the serum be deducted from that obtained for the total blood in the proportion in which red blood-corpuscles and serum are present in the total blood, the result will represent the proteids of the blood-corpus- cles, although only approximately. Estimation of the Red Blood-corpuscles by Weight. Defibrinated blood is mixed with thrice its volume of a concentrated solution of sodium sulphate and filtered. The blood-corpuscles remaining upon the filter are coagulated by immersing the filter in boiling concentrated solution of sodium sulphate. Then the filter can be washed out with distilled water, after which it is dried and weighed. The increase in the weight of the previously weighed filter is due to the presence of the blood- corpuscles. ARTERIAL AND VENOUS BLOOD. Arterial blood contains in solution all those materials that are neces- sary for the nutrition of the tissues, many that are to be employed in secretion and in addition the larger amount of oxygen. Venous blood need contain less of these matters, while the waste materials of the tissues, the products of retrogressive metamorphosis, will be present in greater amount, including a larger quantity of carbon dioxid. As, however, the interchange through the blood takes place rapidly, no great difference in many of these substances can be looked for at a given moment. In many respects analysis fails to furnish conclusive evidence. A little consideration, further, will show that the blood from THE AMOUNT OF BLOOD. 83 some veins must be characterized by special peculiarities, such as the blood from the portal vein and the hepatic veins. The essential differ- ences between the two kinds of blood may be summarized as follows : ARTERIAL BLOOD CONTAINS More Less Oxygen, water, fibrin, extractives, Carbon dioxid, blood-corpuscles, pro- salts, at times chlorids, sugar, fat; teids, alkali, urea, and the temperature is on an average i C. higher. The bright red color of arterial blood is due to oxy hemoglobin, to which it is peculiar; while the dark color of venous blood is due to a deficiency in oxyhemoglobin and an abundance of reduced hemoglobin. The larger amount of carbon dioxid in venous blood is not responsible for the dark color, for if equal amounts of oxygen be added to two portions of blood and to the one also carbon dioxid, the latter effects no change in color. THE AMOUNT OF BLOOD. The amount of blood in the adult equals y 1 ^ of the body- weight, in the newborn --$. According to A. Schiicking the amount of blood in the infant when the umbilical vein is ligated immediately after birth is j^, while that in the infant when ligation is practised later is as much as ^ of the body- weight. Immediate ligation, therefore, causes a reduction of the amount of blood in the newborn child of about 100 grams. Further, the number of red corpuscles is less in the blood of the newborn child after immediate ligation than in that of infants in which ligation is practised later. For the estimation of the amount of blood, first practised by Valen- tine in 1838 and by Ed. Weber in 1850 by unreliable methods, the fol- lowing may be employed : Welckefs Method. Blood from the incised carotid of a previously weighed animal, with a cannula tied in the vessel, is received into a weighed flask, in which it is defibrinated by agitation with pebbles. It is then measured. A portion of the defibrinated blood is made cherry-red by the passage of carbon monoxid, because ordinary blood possesses varying coloring power in accordance with the amount of oxygen present. Now a \- shaped cannula is tied in both extremities of the divided carotid and a 0.9 per cent, solution of sodium chlorid is permitted to flow steadily from a pressure- vessel, while the resulting wash- water that escapes from the divided jugular veins and the inferior vena cava is collected until it becomes as clear as water. Then the entire body is minced, and with the exception of the weighed contents of the stomach and intestines, whose weight is deducted from that of the body, the mass is extracted with water and expressed after the lapse of 24 hours. This water and the sodium-chlorid wash- water are mixed and weighed. A portion of this mixture is likewise saturated with carbon monoxid. Of this a specimen is placed in a glass chamber with parallel walls, i cm. apart a so-called hema- tinometer, while in a second chamber water is added to the undiluted blood from a buret until both fluids exhibit the same shade of color. From the amount of water that is necessary to make the dilution of the blood of the same tint as the wash-water the amount of blood present in the latter can be estimated. In mincing the muscles alone the coloring-matter yielded by them can be considered as muscle-pigment and need not be taken into account. By multiplying the volume of blood by its specific gravity the absolute weight of the blood can be determined. As the differences in the color of the specimens can be esti- mated most accuratelv this method is to be commended. 84 ABNORMAL INCREASE IN THE AMOUNT OF BLOOD. The weight of the blood of mice has been found to be from y^ to -^ of the body-weight, exclusive of gastric and intestinal contents; of guinea-pigs - 1 (from -^ to - 1 ) ; of rabbits ^ (from ~ to -^-) ; of dogs 1 3 (from 4 to ^); of cats ~; of birds from ^ to ^- of frogs ^ to ~; of fish from ^ to ^. Vierordt's method, which is based upon the determination of the amount of blood by indirect means, is discussed under circulation time. The specific gravity also should be determined in a study of the blood. In states of inanition the amount of blood has been observed to be reduced. Obese individuals have relatively less blood. After hemorrhage the blood lost is readily replaced by water, while the blood- corpuscles are only gradually regenerated. After extensive, deple- thoric transfusion with defibrinated blood Landois, as well as Panum, observed the amount of blood and its specific gravity to be maintained. In the living animal Grehant and Quinquaud permitted a measured amount of carbon dioxid to be inspired, then withdrew a quantity of blood and estimated the amount of carbon monoxid present. From this the amount of blood can be readily determined. A quantity of carbon-monoxid blood could also be transfused and shortly thereafter the proportion of shed blood containing carbon monoxid, and that free from carbon monoxid, be estimated. The estimation of the amount of blood in individual organs is made after sudden ligation of their veins during life. The organs are cut up into small pieces and the amount of blood contained in the wash-water is determined by comparison with a specimen of blood to be diluted. The estimation after death in a state of freezing is to be rejected. ABNORMAL INCREASE IN THE AMOUNT OF BLOOD OR ITS INDIVIDUAL PARTS. An increase in the total mass of blood uniformly in all its parts is known as polyemia or plethora. It may occur as a morbid manifestation in individuals with excessive nutritive and assimilative activity. A marked bluish-red color of the external integument, with swollen veins and large arteries and a hard and full pulse, injection particularly of the capillaries and smaller vessels of the visible mucous membranes are the readily explicable signs, accompanied by cerebral hyperemia, which may give rise to attacks of vertigo, and hyperemia of the lungs, which may give rise to dyspnea. Also after amputation of large portions of the extremities, with avoidance of loss of blood, a relative increase in the amount of blood has been described (plethora apocoptica) . Polyemia can be induced artificially by injection of blood from the same species. If the normal amount of blood be increased up to 83 per cent, no ab- normal condition develops; in particular, the blood-pressure does not become permanently raised. The blood finds its way especially into the greatly distended capillaries, which as a result become stretched beyond their normal elasticity. An increase in the amount of blood, however, up to 150 per cent, jeopardizes life directly, with considerable variations in blood-pressure, and which Landois has observed to terminate fatally in consequence of direct rupture of vessels. Following upon the injection of blood the formation of lymph rapidly in- creases. Then the serum is disposed of in the course of one or two days, the water being eliminated principally through the urine, and the proteids in part converted into urea. Therefore, the blood at this time appears to be richer in red blood-corpuscles. The red blood-corpuscles undergo destruction much more slowly and the materials furnished by them are converted in part into urea and in part into the biliary pigment, though not constantly. Nevertheless an excess of red blood-corpuscles may be observed for as long as a month. That as a matter of fact the blood-corpuscles are slowly destroyed in the process of metabolism is shown from the circumstance that the formation of urea is greater when the animal ingests the same amount of blood than if it receives an equal amount by transfusion. In the latter event a moderate increase in ABNORMAL INCREASE IN THE AMOUNT OF BLOOD. 85 the amount of urea persists often for a number of days as a sign of slow destruc- tion of the red corpuscles. Marked plethora is attended, further, with loss of appetite as well as a tendency to hemorrhages from the mucous membranes. Serous polyemia is the name given to that condition of the blood in which the amount of serum or plasma is increased. The condition can be produced artificially by injecting into the veins of animals serum from the same species. Under such circumstances the water is soon excreted with the urine, while the albumin is decomposed into urea, without passing over into the urine. An animal forms more urea from a given amount of injected serum than from an equal amount of blood an indication that the blood-corpuscles are capable of being preserved for a longer time than the serum. If, however, an animal be injected with the serum from another species, in which the blood-corpuscles of the recip- ient undergo solution, as, for instance, if dogs' serum be injected into a rabbit, the blood-cells of the recipient are dissolved and hemoglobinuria develops, and even death may take place if the dissolution be extensive. Simple increase in the amount of water in the blood, aqueous polyemia, occurs as a transitory phenomenon after copious ingestion of fluid, but increased diuresis soon restores the normal conditions. Disease of the kidneys attended with de- struction of the secreting parenchyma of the glands induces, together with aqueous polyemia, often general anasarca through the leakage of water into all of the tissues. Ligation of the ureter likewise gives rise to an increase in the watery elements of the blood. Stint zing and Gumprecht found the dry residue of small amounts of blood after evaporation of the water to be from 19.8 per cent, in women to 21.6 per cent, in men, while in cases of anemia it falls to 8.5 per cent. An increase of the red blood-corpuscles beyond the normal mean polycy- ihemic plethora or hyperglobulia has been thought to be present in robust individ- uals when hemorrhages that have regularly taken place cease and in general all of the symptoms of polyemia are present. The cessation of menstrual, hemorrhoidal, and nasal hemorrhages is considered as a cause, as well as the omission of venesection previously employed systematically. Nevertheless, the poly- cythemia under such circumstances is only inferred and not established by enu- meration. On the other hand, a condition of polycythemia has been positively observed. Thus, after transfusion of blood from the same species a portion of the blood-plasma is soon consumed, while the blood-corpuscles are preserved for a longer time. An increase in the number of red blood-corpuscles up to 8,820,000 in a i cu. cm. in case of severe heart-disease, with marked stasis, in which more water escapes from the vessels by transudation, is a remarkable fact. The num- ber is for the same reason greater also in cases of hemiparesis upon the paralyzed side presenting phenomena of stasis. After attacks of diarrhea that cause a reduction in the amount of water in the blood there is likewise an increase in the number of red corpuscles, and it is probable that the same result is brought about by profuse sweating and by polyuria. Agents that influence the caliber of the vessels, such as alcohol, chloral hydrate, amyl nitrite, give rise to an increase in number when they cause con- traction of the vessels and to a diminution when they cause relaxation. A transitory increase in the ancestors of the red blood-corpuscles is encountered as a reparative process after profuse hemorrhage or after acute disease. In cachectic states the increase is permanent on account of interference with the transformation into red corpuscles. In the last stages of cachectic states the number progressively diminishes, as at this time the production of the ancestral forms also ceases. The designation hyper albuminous plethora has been applied to an increase of the albuminates in the plasma such as it may be inferred occurs after abundant absorption from the digestive tract. The same condition may be induced experi- mentally by injection of serum from the same species of animal, the elimination of urea increasing at the same time. Injection of egg-albumin induces albu- minuria. Melitemia or an excess of sugar in the blood. The sugar of the blood is eliminated in part with the urine, in marked degree up to i kilo daily, and the amount of urine may be increased to 25 kilos. To replace this loss an abundance of nourishment and much fluid are necessary, and in this way the amount of urea may at the same time be increased threefold. The marked pro- duction of sugar also induces destruction of proteid tissue, so that the amount of urea is increased, even if the supply of albumin be insufficient. The patients emaciate, all of the glands, particularly the testicles, undergo atrophy or degenera- 86 ABNORMAL DIMINUTION IN THE AMOUNT OF BLOOD. tion, the skin and the bones become thin, while the nervous system resists the longest. The crystalline lens becomes turbid in consequence of the presence of sugar in the fluids of the eye, which abstract water from the lens. Wounds heal badly on account of the abnormal constitution of the blood. If a drop of blood be spread upon a glass slide, then treated with a solution of Bieberich's scarlet or alkaline methylene-blue and heated for ten minutes at a temperature of 35, it will not take the stain if derived from a case of diabetes, while normal blood is stained. Instead of grape-sugar excessive accumulation of inosite or of milk-sugar has also been found in the blood and in the urine. Lipemia. Increase in the amount of fat in the blood occurs normally after the ingestion of food rich in fat, as, for instance, in nursing kittens, so that the serum itself may acquire a milky turbidity. Pathologically, this is observed in still more marked degree in drunkards and in obese individuals. In conjunction with marked destruction of proteids in the body, therefore, in a large number of wasting diseases, the amount of fat in the blood is increased; likewise after abundant administration of easily digestible carbohydrates, together with much fat, in the food. V. Jaksch found traces of fatty acids in the blood of febrile and leukemic patients. After injuries to bones involving the marrow large numbers of fat-globules often pass from the vessels of the marrow, in part unprovided with walls, into the blood-stream, so that fat may even find its way into the urine, and may give rise to dangerous fat-emboli in the lungs. The salts are usually preserved with great tenacity. If sodium chlorid be withheld, albuminuria results; and if salts in general, paralytic phenomena. Excessive administration of salty food, as in the form of pickled meat, has not rarely been followed by death through fatty degeneration of the tissues, par- ticularly of the glands. Withdrawal of calcium and phosphoric acid brings about softening or atrophy of the bones. In the presence of infectious diseases and of anasarca the amount of salts in the blood has often been found increased, while in the presence of inflammation (sodium chlorid is wanting in the urine in cases of pneumonia) and of cholera the amount is diminished. The amount of fibrin in the blood is increased in the presence of inflamma- tion, particularly of the lungs or the pleura. Therefore venesection under such circumstances is followed by the formation of the so-called buffy coat. The fibrin may be increased also in other diseases attended with blood-destruction. Sigm. Mayer observed an increase likewise after repeated venesection. Blood rich in fibrin usually coagulates more slowly than blood deficient in fibrin, although exceptions to this statement are not wanting. ABNORMAL DIMINUTION IN THE AMOUNT OF BLOOD OR OF ITS INDIVIDUAL CONSTITUENTS. Reduction in the mass of the blood as a whole true oligemia occurs after every direct loss of blood. In the newborn a hemorrhage of even a few cu. cm., in children a year old a hemorrhage of 250 cu. cm., and in adults a loss of one- half of their blood may prove dangerous. Women withstand better than men even considerable loss of the blood. In them the regeneration of the blood appears to take place more readily and more quickly in consequence of the periodic restoration of the blood lost at each menstrual period. Obese persons, as well as the aged and the debilitated, are less tolerant to loss of blood. The hemorrhage is the more dangerous the more rapidly it takes place. General pallor and coldness of the skin, a sense of fear and oppression, relaxation, the appearance of spots before the eyes, roaring in the ears and vertigo, loss of voice and syncopal attacks usually accompany profuse hemorrhage. Dyspnea ("and breathing rapidly he exhales life in a purple stream:" Sophocles' Antigone), cessation of glandular secretion, profound loss of consciousness, then dilatation of the pupils, involuntary discharge of urine and feces, and finally general convulsions are the positive premonitions of rapid death from hemorrhage. In the state of greatest danger life can be saved only by transfusion. As much as one-quarter of the normal amount of blood can be withdrawn from animals without permanently lowering the blood-pressure in the arteries, because the latter by contraction adapt themselves to the smaller volume of blood in consequence of the anemic irritation of the vasomotor center in the medulla oblongata. Loss of blood up to one-third of the volume of blood causes marked reduction in the blood-pressure. Dogs recover after loss of one-half of the volume ABNORMAL DIMINUTION IN THE AMOUNT OF BLOOD. 87 of blood. If two-thirds be removed one-half of the animals die, while the remaining half recover spontaneously. If the hemorrhage does not terminate fatally, the water of the blood, with the dissolved salts, is first replaced through absorption from the tissues, with gradual increase in the blood-pressure; and later the proteids. Considerable time is required for the regeneration of the blood-corpuscles. The blood, there- fore, contains for a time an abnormal amount of water hydremia; and finally it exhibits an abnormal deficiency in cells oligocythemia, hypoglobulia. With the increased lymph-stream toward the blood the leukocytes are soon considerably increased above their normal number. Also fewer red blood-corpuscles appear to be consumed during the period of restitution, as, for instance, in the formation of bile. After moderate venesection in animals Buntzen observed the volume of blood restored in a few hours, and after severe hemorrhage in the course from 24 to 48 hours. The red blood-corpuscles, however, were, after venesection of from i.i to 4.4 per cent, of the body-weight, fully restored to the normal only after the lapse of from 7 to 34 days. The commencement of the regenerative process could be recognized in the course of 48 hours. During this period of reorganization the number of the embryonal forms of the blood-corpuscles was increased. The newly formed blood-corpuscles appear at first to contain less hemoglobin than normal. Also in human beings the duration of the period of regeneration ap- pears to be dependent upon the amount of hemorrhage. The reduction in the amount of the hemoglobin of the blood after venesection is approximately pro- portional to the amount of the blood removed. Of especial significance is the state of metabolism in the body of an anemic patient. The decomposition of proteids is increased, and as a result the elimina- tion of urea is increased. The combustion of fats in the body is, however, correspondingly diminished, and the amount of carbon dioxid given off is cor- respondingly reduced. Anemic as well as chlorotic patients therefore readily put on fat. The same significance is to be attached to the lipomatosis of anemic convalescents after acute diseases interfering with blood-formation. The fattening of animals is, accordingly, favored by occasional venesection. The same statement is applicable to intercurrent hunger. Aristotle had already pointed out that swine and birds readily take on considerable fat after days of intercurrent hunger. Anemia results also from failure on the part of the blood-forming organs. The alarming anemia from the presence of the bothriocephalus, which may pursue a course similar to pernicious anemia is remarkable. It is probably dependent upon a toxic effect induced by the parasite, which impairs the vitality of the blood-corpuscles. Excessive concentration of the blood through loss of water is designated dry oligemia. This condition has been observed in human beings after copious, watery diarrhea, particularly in cases of cholera, and the thick, tarry blood stag- nates in the veins. Probably copious loss of water through the skin as a result of diaphoretic treatment, particularly in association with restriction of fluids, may give rise to dry oligemia, even though only in moderate degree. If the proteids of the blood are diminished in abnormal degree a condition of hy palbuminous oligemia is present. The proteids may be diminished more than half. In their place an excessive amount of water usually finds its way into the blood, so that the salts of the plasma are likewise diminished. Loss of proteids from the blood is due directly to albuminuria, which may furnish even 25 grams of proteid daily; to long-continued suppuration, extensive weeping cutaneous sur- faces, excessive loss of milk, albuminous diarrhea (dysentery). Frequent and copious hemorrhage, also, induces at first hypalbuminous oligemia, as the loss primarily is principally made good by the taking up of water into the vessels. V. Jaksch found that the amount of proteids failed to decline in correspondence with the reduction in the number of blood-corpuscles. PHYSIOLOGY OF THE CIRCULATION. CAUSE, PURPOSE, DIVISION. The blood maintains itself within the vascular system in an unin- terrupted circulating movement that, proceeding from the cardiac ven- tricles through the largest arterial trunks k arising therefrom (the aorta and the pul- monary artery) to the furthermost branches of these vessels, then through a system of capillary vessels, from which it is collected into the venous channels, which progressively increase in size by coalescence, terminates finally in the auricles. The cause of this circulatory movement resides in the difference in pressure to which the blood is exposed in the aorta and the pulmonary artery, on the one hand, and the two venae cavae and the four pulmonary veins on the other. The blood naturally flows continuously toward that portion of the closed system of tubes where the pres- sure is lowest. The greater this difference in pressure the more active will be the move- ment of the stream. Abolition of this differ- ence in pressure, as after death, will natur- ally cause a cessation of the flow. The purpose of the circulation is, on the one hand, to carry nourishment through the blood to all the tissues of the body, while on the other, the blood carries away from the tissues to the organs of excretion the waste products of their metabolism. The circulation of the blood is divided into: 1. The greater circulation, comprising the pathway from the left auricle and the left ventricle through the aorta and its branches, the capillaries and the veins of the body, to the termination of the two venae cavse in the right auricle. 2. The lesser circulation, comprising the pathway of the right auricle and the right ventricle, the pulmonary artery, the pulmonary capillaries and the four pulmonary veins arising therefrom up to their point of entrance into the left auricle. 3. The portal circulation is occasionally considered as a separate circulatory system, although it is only a second capillary ramification 88 FIG. 21. Diagrammatic Representa- tion of the Circulation: a, right auricle; A, right ventricle; b, left auricle; B, left ventricle; i, pulmonary artery; 2, aorta, with semilunar valves; 1, lesser cir- culation; k, greater circulation, including superior vena cava, o; G, greater circulation, including inferior vena cava, u; d d, intesti- nal tract; m, mesenteric arteries; q, portal vein; L, liver; h, hepa- tic veins. THE HEART. 89 inserted into a venous pathway. It is composed of the portal vein, which represents the union of the veins of the abdominal viscera the superior gastric, the superior and inferior mesenteric, and the splenic veins and which breaks up in the liver into capillaries that again unite to form the hepatic veins, which empty into the inferior vena cava. Strictly speaking, this differentiation of the portal system into a separate circulation is not justifiable. In many animals similar conditions are found in still other organs, as, for example, the suprarenal of the snake and the kidney of the frog. When an artery breaks up into numerous small branches that shortly reunite, without the intervention of capillaries, to again form an artery, the cluster of branches thus formed is called a "wonderful network," rete mirabile, such as is seen in apes and edentates. Microscopical networks of this character are found in the mesentery of man. The glomerulus of Bowman's capsule in the kidney also is an example of this peculiar arterial division. Analogous formations in the veins are called venous "wonderful networks." THE HEART. The mammalian heart-muscle (Fig. 184, 8) is composed of short, closely and finely striated, unicellular elements which are devoid of sarcolemma and, in man, from 50 to 70 // long and from 15 to 23 /u wide. The ends are rather blunt and generally split, and by these split ends the fibers are joined together anastomotically to form a network. The individual muscle-cells are united by a cement-substance, which is soluble in 33 per cent, potassium-hydrate solution and is stained black by silver nitrate. Each cell at its center contains a nucleus, rarely two smaller nuclei, 14 u- long by 7 // wide, in its central axis. The transversely striated sub- stance frequently contains molecular granules arranged in rows. The fibrils are placed side by side and are divided by the perimysium into bun dies, which, after solution of the connective tissue by boiling, may be isolated. The shape of the bundles on transverse section is rather circular in the auricles, while in the ventricles it is rather flat and laminated; here also several of the smaller bundles may unite to form a thicker band. The interstices between the bundles serve to carry the lymph-vessels. ARRANGEMENT OF THE MUSCLE-FIBERS OF THE HEART AND THEIR PHYSIOLOGICAL SIGNIFICANCE. Musculature of the Auricle. The study of the embryonal heart furnishes the key to the understanding of the complicated arrangement of the muscle-fibers. The simple heart-tube of the embryo exhibits an outer circular and an inner longitudinal layer of muscle-fibers. The septum is formed later, so that it is obvious that both in the ventricles as well as in the auricles the fibers belong, in part at least, to both halves, as they originally enclose only a single cavity. On the other hand, the fibers of the auricles are generally separated from those of the ventricles by the fibrous ring; nevertheless certain of the muscle-bundles pass from the auricles to the ventricles. In the auricles the embryonal arrange- ment of the fibers remains fundamentally unchanged. In the ventricles the arrangement is obliterated because during the process of development the fibers here undergo a peculiar bending and looping, as in the stomach, together with a spiral rotation. The musculature of the auricles is in general arranged in two layers: an outer transverse, which is continuous over the two auricles, and an inner longitudinal. The outer fibers can be traced from the entering veins upon the anterior and posterior walls. The inner fibers are especially prominent where they are attached vertically to the fibrous rings, but in certain parts of the anterior wall in particular they are not arranged continuously. On the septum of the auricles the ring-like muscular layer surrounding the oval fossa, the opening of the oval foramen in the embryo, is especially prominent. Around the openings of the veins emptying into the auricles are found circular muscle-bundles; these are least well marked around the inferior cava, while- around the superior cava they are well developed and extend upward around the vessels for 2.5 cm. (Fig. 22, II). At the entrance of the four pulmonary veins in man and in some mammals, transversely striated muscle-fibers, arranged in an inner circular and an outer longitudinal layer, ex- 90 MUSCULATURE OF THE VENTRICLES. tend upon the pulmonary veins as far as the hilus of the lung; in other animals (apes, rats) they extend even into the lung itself; indeed, in some mammals (mouse, bat) this muscular layer penetrates the lung so far that in the small veins the entire wall is composed almost wholly of striated muscle-fibers. Muscle- fibers, chiefly circular, are also found at the termination of the great cardiac vein and in the coronary valve of Thebesius. Many elastic fibers are present in the perimysium of the auricles. From the physiological standpoint the foregoing anatomical data explain the following facts with relation to the contractions of the auricles. The auricles are able to contract independently of the ventricle's; this is particularly manifest in the cessation of the heart's activity, as under such circumstances two or more contractions of the auricle alone are often seen to take place, followed now and then by a single con- traction of the ventricle. However, when the action of the heart is n FIG. 22. I, Course of the Muscle-fibers in the Left Auricle: the outer transverse and the inner longitudinal fibrous layer are visible and in addition the circular fibers of the pulmonary veins, v.p. V, left ventricle (Joh. Reid). II, Distribution of Transversely Striated Muscle-fibers on the Superior Vena Cava (Elischer): a, entrance of the azygos vein; v, auricle. unimpaired the auricles in their contraction transmit the motor impulse to the ventricles. Whether this stimulation is brought about through nerve-fibers or, as is more probable, through connecting muscle-bundles, has not yet been decided with certainty. The two chief layers of fibers (transverse and longitudinal), which cross each other, serve to effect uniform contraction of the auricular cavity from all sides, as is the case likewise with most hollow muscular organs. The circular fibers surrounding the entering venous trunks, through their contraction, which occurs in unison with that of the auricles, cause in part an emptying of blood into the auricle and in part a hin- drance to a return of the blood in any considerable measure. ARRANGEMENT OF THE MUSCULATURE OF THE VENTRICLES. The Muscle-fibers of the Ventricles. Beneath the pericardium there is first met an outer longitudinal layer (Fig. 23, A), consisting of only occasional bundles on the right ventricle, while on the left it comprises a compact layer of about one-eighth of the entire thickness of the wall. A second layer of longitu- dinal fibers lies on the inner surface of the ventricles, being especially well marked at the orifices, as well as inside the perpendicularly placed papillary muscles, PERICARDIUM; ENDOCARDIUM; VALVES. 91 while in other situations it is replaced by the irregularly running fibers of the muscular trabeculae. Between the two longitudinal layers lies the most powerful transverse layer, the fibers of which are separable into individual, leaf -like, ring-shaped bundles. The three layers, however, are not wholly independent and separated from each other, but rather there is a gradual transition between the transverse and the outer and inner longitudinal layers by means of oblique fibers. The common assumption is that the entire outer longitudinal layer passes gradually into the transverse and this in turn wholly into the inner longitudinal, as is shown diagrammatically in Fig. 23,0. This is not justifiable, and is negatived by the great preponderance in the thickness of the middle layer. In general the outer longitudinal fibers pursue such a course as to intersect the course of the fibers of the inner longitudinal layer at an acute angle. The intervening trans- verse layer constitutes the medium for a gradual transition between these courses. FIG. 23. Course of the Muscle-fibers in the Ventricles: A, course upon the anterior surface; B, view of the apex with the "whirl" (Henle); C, diagrammatic representation of the course of a muscle-fiber within the wall of the ventricle: D, course of such a fiber into the papillary muscle (C. Ludwig). At the apex of the left ventricle external longitudinal fibers, uniting in the so-called "whirl" (B), pass in a curved direction inward and upward within the muscle-substance and extend into the papillary muscles (D). Nevertheless it is an error to consider that all of the ascending fibers in the papillary muscles are derived from these vertical muscle-bundles of the outer surface, as many arise independently from the wall of the ventricle. Neither can the origin of these longitudinal fibers on the outer surface of the heart be traced solely to the fibrous rings or to the roots of the arteries. Finally, mention should be made of the special circular layer of fibers that surrounds the left orifice like a sphincter. Numerous lymph-vessels are present in all the interstices between the muscle-fibers and the blood-vessels. These eventually empty into the lymph- vessels and nodes of the mediastinum. PERICARDIUM ; ENDOCARDIUM ; VALVES. The pericardium, which includes between its two layers a lymph-space the pericardial cavity containing a small amount of lymph, exhibits the structure of a serous membrane; that is, it is composed of connective tissue containing delicate 92 PERICARDIUM; ENDOCARDIUM; VALVES. elastic fibers, and is covered on its free surface with a single layer of irregular polygonal, flat, endothelial cells. A rich network of lymph-vessels lies within the pericardium itself, as well as more deeply toward the muscle-mass of the heart. Stomata are wanting in both layers of the pericardium. In the subserous tissue of the pericardium, especially in the sulci for the coronary vessels, are deposits of fat, and lymphatics. The endocardium presents all of the characteristics of a vessel-wall. Facing the cavity of the heart, there is first a single layer of flat, polygonal, nucleated endothelial cells. Then there comes, as the true groundwork of the whole mem- brane, a layer of delicate elastic fibers (more marked in the auricles, and even forming a f enestrated membrane) , in the midst of which but little connective tissue occurs. The latter, much more loosely arranged and intermixed with elas- tic fibers, is present in larger amount toward the heart-muscle. Scattered bundles of unstriated muscular fibers, usually arranged longitudinally, are found between the elastic elements (in smaller amount in the auricles) . These obviously have the task of combating the pressure and the tension exerted on the endocar- dium during the cardiac contraction; for wherever throughout the body a wall composed of soft parts is exposed to repeated high pressure muscular elements are found, and never elastic tissue alone. The endocardium is non- vascular. The valves both the arterial (semilunar) and the venous (mitral and tricuspid) also are a part of the endocardium. The venous and arterial orifices on the right side are separated from each other in the wall of the ventricle, while the two orifices on the left are united into a single large opening. The valves are attached to their basal margins by means of resistant fibrous rings composed of connective-tissue and elastic fibers. They consist of two layers: (i) The fibrous, which is a direct continuation of the fibrous ring, and (2) a layer of elastic elements. The elastic layer of the auriculo-ventricular valves is a direct prolongation of the endocardium of the auricle, and is therefore directed toward that cavity. At their bases the valves are united by their adjacent margins. The tendinous cords are inserted on the free margin and on the under surface of the valves. The semilunar valves possess a thin, elastic layer, thickened at their base and turned toward the arteries. The auriculo-ventricular valves contain also striated muscle-fibers. Radiating fibers, arising from the auricles, extend into the valves, and it is their function in part to retract the valves toward their bases during the time of auricular systole, and thus to enlarge the passage-way for the flow of blood into the ventricles. Paladino describes still other longitudinal fibers derived from the ventricles. Besides these, there is directed rather [toward the ventricular aspect, a con- centric muscular layer, following the basal attachment of the valves, which appears to have a sphincter-like action drawing the bases of the valves together during the period of ventricular contraction when the valves are under tension, and thus preventing excessive distention. The larger of the tendinous cords also contain striated muscle-fibers; and the Thebesian and Eustachian valves like- wise contain a delicate muscular network. The name "Purkinje's fibers" has been applied to a grayish network of muscular elements found in mammals and in birds chiefly beneath the endocar- dium of the ventricle, but occurring also in the muscular mass itself. These appear to represent a stage of embryonal development (on account of the partial striation) . They are absent in man and in the lower vertebrates. Blood-vessels occur in the auriculo-ventricular valves in considerable number only where there are muscle-fibers. In children delicate vessels extend to the free margin of the valve. The semilunar valves are devoid of blood-vessels except under pathological conditions. A network of lymphatics extends from the endo- cardium to the middle of the valves. Weight and Size of the Heart. According to W. Muller, the weight of the heart in children and in older persons having a body- weight up to 40 kilos, is 5 grams for every kilo of body-weight ; in individuals having a body-weight of from 50 to 90 kilos, the proportion is 4 grams of heart for each kilo; in individuals having a body-weight of 100 kilos, 3.5 grams of heart for each kilo of body-weight. The auricles become stronger with increasing age. The right ventricle weighs half as much as the left. In man the heart weighs 309 grams; in woman, 274 grams. Blosfeld and Dieberg found the heart in man to weigh 346 grams; in woman, from 310 to 340 grams. The thickness of the left ventricle in man aver- ages 11.4 mm.; in woman, 10.15 mm.; the thickness of the right ventricle, 4.1 and 3.6 mm. respectively. THE CORONARY VESSELS. 93 THE CORONARY VESSELS; AUTOMATIC REGULATION, NUTRI- TION, AND ISOLATION OF THE HEART. With reference to the origin of the coronary arteries the question at once arises whether the orifices of these vessels are closed by the eleva- tion of the semilunar valves during systole as a result of the application of the valve-leaflets to the walls of the vessels or whether such occlusion does not take place. Anatomical. The two coronary arteries arise from the region of the sinus of Valsalva. The point of origin varies: (i) It is either within the concavity of the sinus; or (2) the mouths of the vessels are not completely within the range of the margin of the valve, and this is frequently the case with the left coronary of man and the ox; or (3) the orifices project beyond the margins of the valve (this is rare). These findings alone make it improbable that closure of the mouths of the coronary arteries by the semilunar valves during ventricular systole is a constant physiological phenomenon. AUTOMATIC REGULATION OF THE HEART. According to Briicke the openings of the coronary arteries are covered by the semilunar valves during systole, so that they can be filled only during diastole. The advantage of this arrangement resides in the fact that (a) the diastolic distention of the ventricular vessels stretches the muscular fibers of the ventricular wall and thus corre- spondingly dilates the ventricle for the reception of the blood that pours in from the auricle during diastole. (6) On the other hand, the systolic distention of the coronary arteries would be useless because the dilatation of the ventricular wall (due to the distention of the arteries already mentioned) would resist the systolic contraction, and because the systolic distention of the coronary arteries and the expulsion of the blood from them would unnecessarily diminish the power of the ventricle. Accordingly, the diastolic distention of the coronary arteries* would be most consistent with the mechanical conditions present. This mechanism Briicke has designated the "auto- matic regulation of the heart." FIG. 24. Semilunar Valves, Closed. Semilunar Valves, Opened. This theory and its underlying principles are untenable, for 1. The filling under high pressure of the coronary arteries of a dead heart not only is followed by no dilatation, but actually causes a contraction of the cavity of the ventricle. 2. The chief branches of the coronary arteries lie in the sulci of the heart embedded in the loose subpericardial fatty tissue, where their dilatation and con- traction could scarcely have any effect upon the size of the cavities of the heart. 3. Brown-S6quard found in animals and v. Ziemssen in a woman with a large deficiency in the wall of the left thorax that the coronary pulse was synchronous with that in the pulmonary artery. Newell-Martin and S'edgwick, by introducing manometers into the coronary and carotid arteries of a large dog, obtained simul- 94 AUTOMATIC REGULATION OF THE HEART. taneous pulsatory elevations. In accordance with these observations is the fact that an incised coronary artery spurts continuously, with systolic exacerbations, as do all other arteries/ 4. If a strong stream of water is passed intermittently through a sufficiently large tube introduced into the left auricle of a fresh pig's-heart, and it is forced, through the auriculo-ventricular orifice on into the aorta; and if the aorta beyond its arch is connected with a large tube directed upward (in order to establish pressure in the aorta) , the water will be seen to spurt continuously from the divided coronary artery, with systolic exacerbations. 5. There is constantly present in the sinuses of Valsalva an amount of blood sufficient to fill the arteries in question during systole. 6; The valves when elevated are not applied closely against the wall of the aorta, even with the greatest amount of pressure that can be exerted by the ventricle. On the contrary, there remains between each valve-leaflet and the aortic wall a semilunar space filled with blood, as is shown in Fig. 24. 7. Undoubted cases of extensive destruction of the semilunar valves that with certainty render closure of the mouths of the coronary arteries impossible are directly opposed to this theory. 8. Observations on muscle have shown that during contraction its small vessels undergo dilatation and the blood-stream through it is accelerated. It is, therefore, difficult to believe that in the contracted heart-muscle the movement of the blood should cease. As, during the systole, the small arterial branches lying close to the ventricular cavity are exposed to a pressure greater than that of the aorta a systolic compression of their lumen occurs, with a forcing out of their contents in the direction of the veins. The ventricular con- traction thus aids the flow of the blood in the coronary vessels ; marked dilatation of the heart diminishes it. The capillary vessels of the myocardium are numerous in correspond- ence with the energetic activity of the heart; they, like the small vessels generally, lie within the muscle-bundles in contact with the muscle- cells. With their transition into veins several of them coalesce almost at once to form a large vein, from which the extremely easy passage of the blood into the veins is readily understood. The veins are provided with valves. As a result it happens that (i) with 'the systole of the right auricle (therefore during the ventricular diastole) the venous stream is interrupted; (2) with contraction of the ventricle the flow of blood in the cardiac veins is accelerated in the same way as it is in the veins of the muscles. This systolic acceleration of the venous flow permits of the conclusion that the arterial circulation is not interrupted at this time. The coronary arteries, between which no anastomoses occur, are characterized by the great thickness of their elastic and connective-tissue intima, and this per- haps explains the frequency of calcification in these vessels. Many of the lower vertebrates have no vessels in the heart-substance (anangiotic hearts) for example, the frog; but this statement is disputed. The motor disturbances and even the complete cessation of action that have been observed in the heart after partial or complete occlu- sion of the coronary vessels are of importance, particularly as analogous conditions are observed in man in consequence of occlusion or narrowing of the coronary arteries (for example, as a result of calcification). Method. In rabbits, under the influence of curare and with artificial respira- tion, or after previous section of the vagi (in order to exclude the inhibitory influence of this nerve), it is possible to clamp off the coronary arteries close to their origin from the aorta with a spring clamp. Ligation is less satisfactory, as it cannot be accomplished without wounding the heart. In dogs it is possible to push a glass rod provided with a button-like extremity from the subclavian AUTOMATIC REGULATION OF THE HEART. 95 artery into the mouth of a coronary artery. Injections of various substances capable of causing occlusion have also been tried. In 1867, v. Bezold noted in rabbits after clamping off the coronary artery that the heart-beat grew rapidly smaller and smaller; then the contractions occurred in groups, periodically; later on the regular movement of the ventricle ceased entirely, and in its place the muscle- wall exhibited a peculiar fibrillary contraction; finally the heart stood still. As the circulation was reestablished after removal of the clamp, the phenomena appeared in reverse order until the heart regained its normal beat. If in a dog the right descending coronary artery and the circumflex artery, together with the artery of the septum, are occluded, the heart soon ceases to beat. The closure of only two of the three arteries caused a cessation of contraction in 9 out of 14 animals; while closure of the septal artery or of the right coronary artery alone had no effect. In almost all instances the auricles likewise cease beating. The heart of a dog that has once ceased to beat recovers only with great difficulty. It appears that the fibrillary contractions are due to irritative injury in- flicted during the operation, and not alone to the stasis of the blood. If in rabbits only the left coronary artery is occluded the beat of the left heart is slowed and weakened, while the right heart pulsates without change. As a result it occurs that the left half of the heart can no longer empty itself completely, so that particularly the left auricle becomes filled to distention with blood, while at the same time the unaffected right heart continues to drive blood into the lungs. In consequence edema of the lungs develops as a result of the high pressure in the lesser circulation which is transmitted from the right heart through the pulmonary vessels into the left auricle. According to Sig. Mayer persistent dyspnea has a similar effect, with earlier weakening of the left than of the right ventricle; the pulmonary edema preceding death can be explained in this manner. The heart in the higher animals can maintain its activity only when the circulation of blood through its walls is maintained. The heart from which the blood is completely removed rapidly ceases to con- tract. The coronary circulation must convey the necessary oxygen and nutritive materials to the myocardium, as well as remove the metabolic products from it. The excised "isolated" mammalian heart, which is fed at body-heat through the coronary vessels with bright-red blood, remains active. Langendorff maintains the circulation in the isolated heart by allowing the coronary arteries to be filled from the aorta. Other fluids, for example, lake- colored blood or serum, are incapable of maintaining the heart's activity. At most, such solutions (as, for example, alkaline salt-solution mixed with egg-albu- min 1000 albumin diluted with water, o.i sodium chlorid, o.i calcium chlorid, 0.075 potassium chlorid), in so far as they exert a slightly irritating effect, are capable of stimulating the heart for a time. If the heart is placed in pure oxygen the pulsation may be maintained for a considerable time by passing serum through the cardiac vessels. Also the isolated frog's heart can be included in a circulation by means of suitable tubes. To maintain its contractions oxygen and nutritive fluid are necessary to distend its cavities. This object is best fulfilled by arterial blood; indifferent fluids (0.6 percent, sodium chlorid) quickly bring about a condition of "apparent death," from which, however, the organ can be revived by nutritive fluids. 9 6 THE MOVEMENTS OF THE HEART. The frog's heart is less readily exhausted than that of the higher vertebrates.- Serum-albumin, alkaline salt-solutions of blood, or of milk, made slightly viscid with albumin or gum arabic and sattirated with oxygen, are capable of main- taining the activity of the heart for a long time. Pathological. In the presence of so-called sclerosis of the coronary arteries in old age there occur acute or chronic attacks of cardiac disability. Weakness of the heart, alterations in rhythm and frequency (to 8 in a minute), constitute, together with dyspnea, syncope, stasis, attacks of pulmonary edema, the most characteristic phenomena ; and they may terminate in death from so-called heart- failure. In a case of occlusion of the left coronary artery in a man Hammer saw the pulse fall from So to 8, the beats being interrupted by spasmodic vibra- tion. THE MOVEMENTS OF THE HEART. VARIATIONS IN TONE. Method. In addition to direct observation, the kinematograph may be used to great advantage for recording and projecting the movements of the heart, par- ticularly at a slow rate. S.a.-D.v. D.a.-S.v. FIG. 25. Diagrammatic Representation of the Auricular Systole with Ventricular Diastole, and of Auricular Diastole with Ventricular Systole. The movement of the heart is appreciable as alternate contraction and relaxation of the heart- walls. The entire motor phenomenon designated the cardiac cycle consists of three parts: contraction of the auricles (auricular systole); contraction of the ventricles (ven- tricular systole), and the pause, during which the auricles and the ven- tricles are relaxed (diastole). During the contraction of the auricles the ventricles are at rest, during the contraction of the ventricles the auricles are relaxed. The following phenomena can be noted successively during a cycle of the heart : (A) The blood streams into the auricles, which in consequence are- distended. The cause for this resides in: THE MOVEMENTS OF THE HEART. 97 1. The pressure of the blood in the venae cavae (on the right) and the pulmonary veins (on the left), which is greater than the pressure within the auricles. 2. The elastic traction of the lungs, which after the completed con- traction tends to separate the relaxed yielding walls of the auricles lying in contact with each other. The auricular appendages are distended coincidently with the auricles. The appendages serve in a measure as reservoirs for the auricles, to accommodate the large amount of blood flowing in from the veins. (B) The Auricles Contract. There occur in rapid sequence: 1. The contraction and evacuation of the auricular appendages in the direction of the auricle. Simultaneously, the entering veins are con- stricted by the contraction of their circular muscular layers, especially the superior vena cava and the site of entrance for the pulmonary veins. 2. The walls of the auricles contract rapidly in a wave-like manner from above downward, particularly toward the auriculo-ventricular orifices, in consequence of which 3. The blood is forced downward into the relaxed ventricles, which now become considerably dilated. As a result of the auricular con- traction there occur: (a) A slight stasis of the blood in the large venous trunks, such as can be readily observed particularly in rabbits on exposure of the point of junction of the jugular and subclavian veins after division of the muscles of the chest. There is no actual reflux of the blood, but only a slight stasis due to partial interruption of the flow into the auricle, because, as has been stated, the sites of entrance for the veins are nar- rowed; because, further, the pressure in the superior vena cava and in the pulmonary veins soon counteracts the tendency to regurgitation ; and, finally, because in the further ramifications of the inferior and to some extent also of the superior cava and of the cardiac veins, valves prevent the reflux. In the blood thus stagnated in the venae cavae the movement of the heart causes a regular pulsating phenome- non that, when abnormally increased, may give rise to the appearance of a venous pulse. (6) The principal motor effect of the auricular contraction is the distention of the relaxed ventricles, which in small measure are dilated by the elastic traction of the lungs. Earlier and later investigators have attributed the distention of the ven- tricles in part to the elasticity of the muscular walls. It has been thought that the strongly contracted ventricular walls, like a compressed rubber bulb, in re- turning to their resting normal shape, through their own elasticity, aspirate the blood with negative pressure. Such suction-power on the part of the ventricle is, however, effective only in slight degree, if at all. (c) With the distention of the ventricles the auriculo-ventricular valves at once float upward (Fig. 26), being in part forced up by the counter-stroke of the blood from the wall of the ventricle; in part they are capable, by reason of their lower specific gravity, to spread out and float horizontally; in part, finally, they are drawn upward by the longi- tudinal muscular fibers passing from the auricles upon the valves. (C) The ventricles now contract and the auricles relax. In this phase i. The muscular walls contract on all sides and reduce the size of the ventricular cavity. 7 9 8 THE MOVEMENTS OF THE HEART. 2. At the same time the blood presses against the under surface of the auriculo- ventricular valves, the inverted margins of which interdigitate and become hermetically applied to one another (Fig. 26). The valve-leaflets are prevented from being forced back into the auricular cavity, because the tendinous cords hold their under surface and margins firmly like an inflated sail. The approximation of the edges of adjacent valves is favored further by the circumstance that the tendinous fibers always pass from one papillary muscle to the edges of two opposed valves. To the extent that the lower ven- FIG. 26. Plaster Cast of the Ventricles of the Human Heart, Viewed from Behind and Above. The walls are removed, only the fibrous rings and the auriculo-ventricular valves being retained: L, left; R, right ventricle; S, situation of the septum; F, left fibrous ring, with closed mitral valve; D, right fibrous ring, with closed tri- cuspid valve; A, aorta, with the left (ci) and the right (c) coronary artery; 5, sinus of Valsalva; P, pul- monary artery. tricular wall approaches the valves during contraction and thus might render possible a bulging backward of the valves into the auricle, com- pensation is provided by the shortening of the papillary muscles and of the large muscle-containing tendinous cords themselves. The valves when closed present an approximately horizontal surface. There re- mains, therefore, in the ventricles, even at the height of contraction, always a remnant of blood, the so-called residual blood. 3. When the pressure in the ventricle exceeds that in the arterial PATHOLOGICAL DISTURBANCE OF FUNCTION OF HEART. 99 vessels, the semilunar valves are opened, become stretched like tendon above their concave sinuses (Fig. 24), without becoming applied to the arterial wall, and allow the blood to enter. Goltz and Gaule found, by means of maximal and minimal manometers, a negative pressure in the ventricles during a certain phase of the heart's con- traction amounting in the dog to 23.5 mm. of mercury in the left ventricle. They suspected that this phase coincided with the diastolic dilatation and for which they thus assumed a considerable power of aspiration. Moens is of the opinion that this negative pressure prevails in the ventricle shortly before the systole has reached its maximum. He explains the aspiration as being produced by the formation of a vacuum in the ventricle, which must develop as a result of the active movement of the blood, through the aorta and the pulmonary artery, behind the circulating mass of blood, therefore in the ventricle. Gaule and Mink believe that the systolic enlargement of the aorta must at the same time cause a dilatation of the conus arteriosus of the left ventricle. (D) After the ventricular contraction has attained its height and relaxation has commenced, the semilunar valves close with an audible sound (Fig. 27). The diastole of the ventricle is followed by the pause. Under normal conditions the two halves of the heart contract and relax simultaneously and uniformly. The heart-muscle exhibits in its activity certain variations in tone, that is, it does not with every systole contract from the same degree of relaxation to the same degree of contraction, but, rather, there follow in rhythmical periods series of contractions that arise from a considerable degree of relaxation of the heart-muscle, alternating with series of contractions that begin in a less com- plete degree of relaxation. With the latter the degree of contraction is greater than with the former. These variations in tone have been found especially in the auricle of the tortoise-heart. When the arterial blood- pressure is moderately increased, the heart expels a larger amount of blood; if, however, the arterial pressure is greatly increased, the amount of blood expelled at each systole becomes less. Extracts of testicle, suprarenal gland, pituitary gland and spleen in 0.7 per cent, sodium-chlorid solution added to blood exert a tonic effect upon the heart; the extent of the contractions increases and the beats become more regular. Under the influence of alcohol the heart FIG. 27. The Closed Pulmonary exhibits a marked degree of relaxation and a low v^'i 11 ^ Valv f s * Man degree of contraction. The influence of various poi- sons is variable. Heat increases the variations in tone. Whether the relaxation of the heart-muscle is an active dilatation or not has been decided in the affirmative by some investigators. Stimulation of the vagus (likewise digitalis and strychnin) is said to increase the active dilatation; while section of the vagus (likewise atropin) is said to diminish it. PATHOLOGICAL DISTURBANCE OF THE FUNCTION OF THE HEART. All obstructions to the blood-flow through the different portions of the heart or of the vessels connecting them give rise to a permanent increase in the work of that portion of the heart especially concerned with relation to the affected section of the circulation, and in consequence to an increase in the thickness of the muscular walls, with dilatation of the cavity. Should the resistance affect not alone one section of the heart, but consecutively other parts further on in the course of the blood-stream, these also will undergo secondary hypertrophy. If, in addition to increasing the muscle-substance of the affected portion of the heart, its cavity is at the same time dilated, as is often the case, the condition is designated excentric hypertrophy, or hypertrophy with dilatation. The obstructions under consideration in the domain of the vascular channels are: constriction (stenosis) of the arterial 1 or venous orifipes arid likewise defective IOO THE APEX-BEAT. THE CARDIOGRAM. closure (insufficiency) of the valves. The latter causes resistance to the blood- flow by permitting regurgitation of a portion of the blood already propelled onward. In this way there results: 1. Hypertrophy of the left ventricle from hindrances to the blood-flow in the territory of the greater circulation, chiefly in the arteries and capillaries, not in the veins. In this category belongs stenosis of the aortic orifice and of the aorta further on; also calcification and loss of elasticity in the large arteries, irregular dilatations of the arterial walls (aneurysm) ; insufficiency of the aortic valves, as a result of which the left ventricle is continually subject to the aortic pressure; finally, affections of the kidney, in consequence of which a greater arterial pressure is required in order that the urine may be excreted. In the presence of mitral regurgitation also, hypertrophy of the left ventricle is necessary for compensation, and a similar enlargement occurs in the left auricle in conse- quence of the heightened pressure in the lesser circulation. 2. Hypertrophy of the left auricle results from mitral stenosis and from mitral regurgitation, and also consecutively to aortic regurgitation because the auricle must overcome the uninterrupted aortic pressure that is present in the left ventricle. 3. Hypertrophy of the right ventricle results from (a) hindrances to the blood-flow in the territory of the lesser circulation. These are : (a) atrophy of vascu- lar areas of considerable size in the lungs in consequence of destruction, contrac- tion or compression of the lungs and from loss of numerous capillaries in emphysematous lungs. (/?) Overdistention of the lesser circulation with blood in consequence of stenosis of the mitral orifice or of insufficiency of the mitral valve ; also consecutively to hypertrophy of the left auricle resulting from aortic regur- gitation. (b) Hypertrophy of the right ventricle must occur also in conjunction with insufficiency of the pulmonary valves, which permits the blood to regurgi- tate into the ventricle, so that the pressure of the pulmonary artery prevails continually in the cavity. This condition is exceedingly rare. 4. Hypertrophy of the right auricle develops consecutively to the condition last mentioned, likewise in association with stenosis of the right auriculo-ventricu- lar orifice, or from insufficiency of the tricuspid valve. This condition is un- common. When several obstructions in the circulation occur together there is a combination of the resulting phenomena. O. Rosenbach has investigated the manner and method by which the heart maintains its activity after the occur- rence of valvular lesions. If the aortic valves were perforated, with or without simultaneous injury to the mitral and tricuspid valves, the heart performed first an increase of work, which counteracted the physical defects, so that the blood- pressure did not fall. The heart, therefore, possesses reserve powers, which are brought into play only when they are required. In consequence of the valvular insufficiency dilatation first develops as a result of the regurgitation of blood into the affected chamber of the heart. Then follows hypertrophy, but until this is completed the compensation must be effected by the reserve power. Under the conditions that especially render diastole difficult there should yet be mentioned : large effusions into the pericardial sac or pressure on the heart from tumors. The systole is greatly interfered with by adhesions between the heart and the connective tissue of the mediastinum. Under such circumstances the surrounding tissues, even the thoracic wall, must be drawn upon with each con- traction of the heart, so that systolic retraction and diastolic projection occur in the situation of the apex-beat. THE APEX-BEAT. THE CARDIOGRAM. By the term apex-beat (ictus s. impulsus cordis) is understood the visible and palpable elevation of a circumscribed area of the fifth (less commonly the fourth) left intercostal space, caused by the action of the heart. At times the apex-beat is less distinct, especially when the heart strikes against the fifth rib itself. Changes in the position of the body alter somewhat the situation and the force of the apex-beat. A graphic representation of this movement can be obtained by means of a registering apparatus the apex-beat tracing or the cardiogram. Method. To obtain a tracing of the apex-beat the cardiograph of Marey may be.employed. ,The iitstrume,nt has beentmodified by various investigators. The THE APEX-BEAT. THE CARDIOGRAM. 101 pansphygmograph of Brondgeest is essentially the same as Marey's apparatus, with unimportant changes. Marey's sphygmograph can also be used. In animals the cardiogram can be registered by ligating the tube of the pansphygmograph in the pericardium. In the normal tracing of the apex-beat of man (A) or of the dog (B) the following details are distinguishable : a b corresponds to the period of the pause and of the contraction of the auricles. As the auricles con- tract in the direction of the heart's axis from the right and above to the left and downward it is not surprising that the apex of the heart advances toward the intercostal space. In this portion of the tracing there can be seen generally two or even three slight elevations which may be due to the rapidly successive contractions of the venous endings, the auricular appendages, and the auricles themselves. Kill FIG. 28. A, Normal apex-beat tracing from man. B, from a dog; C, tracing of an accelerated apex-beat from a dog; D and E, normal apex-beat tracings from man recorded upon a vibrating tuning-fork plate. Each serration represents 0.01613 second of time. In all of the tracings a b indicates the auricular contraction, b c, the ventricular contraction; d, the closure of the aortic valves; e, the closure of the pulmonary valves; e f, relaxation of the ventricles. Naturally the last, occasionally distinct, elevation, occurring shortly before b (corresponding to B v and C v in Fig. 31), will be looked upon as the true auricular contraction; v. Ziemssen and Ter Gregorianz were able to register the elevation of the auricular appendix preceding the auricular contraction in a woman with an exposed heart. The line b c is caused by the ventricular contraction. It is this alone that is appreciable to the palpating finger as the apex-beat. The first sound of the heart commences with the beginning of the ventricular contraction. 102 THE APEX-BEAT. THE CARDIOGRAM. The cause of the ventricular impulse resides in the following factors : 1. The base of the heart (the junction of auricles and ventricles), which in diastole presents the form of a transverse ellipse (Fig. 29, I, F G), is contracted to a rather circular figure (a b). In this way, the large diameter of the ellipse (F G) is naturally diminished and the small diameter (d c) is increased, and in consequence the base is brought nearer to the chest-wall (e). This alone, however, does not produce the apex- beat, but the base of the heart, thus brought somewhat nearer the chest- wall, and hardened during systole, affords the apex the possibility of making the movement that constitutes the apex-beat. 2. The ventricles, which during the period of relaxation have their apex (Fig. 29, II, i) directed obliquely downward in the line of their long FIG. 29. I. Horizontal Section through the Heart and the Lungs, Together with the Chest-walls, for the Demon- stration of the Change in the Shape of the Base of the Heart during the Contraction of the Ventricles: F G, transverse diameter of the ventricles during diastole; c, position of the anterior ventricular wall; a b, transverse diameter of the ventricles during systole with e, the position of the anterior ventricular wall during systole. II. Lateral View of the Position of the Heart: i, the apex-beat during diastole; p, during systole (in part after C. Ludwig and Henke). diameter, so that the angles (b c i and a c i) formed by the junction of the ventricular axis with the diameter of the base are unequal, represent a symmetrical cone, with its axis perpendicular to its base. Accordingly, the apex (7) must be elevated from below and behind for- ward and upward (p) (W. Harvey: "Cor sese erigere"), and it thus thrusts itself, hardened during systole, into the intercostal space (Fig. 29, II). 3 . During the systolic contraction the ventricles of the heart undergo a slight spiral rotation about their long axes ("lateraleminclinationem," W. Harvey), so that the apex is carried from behind slightly forward, THE APEX-BEAT. THE CARDIOGRAM. 103 while at the same time a considerable area of the left ventricle is turned forward. This rotation is due to the fact that many of the fibers of the ventricular muscles that arise from the portion of the fibrous ring that is turned toward the chest-wall at the junction of the right auricle and ventricle pass obliquely from above and to the right downward and to the left, in part to the posterior aspect of the left ventricle. Thus, they draw the apex of the heart upward in the direction of their course, and its posterior aspect slightly toward the anterior wall of the thorax. This rotatory movement is favored by the circumstance that the aorta and the pulmonary artery, which are applied to each other in a slightly spiral manner, effect a rotation of the heart in the same direction at the time of systolic tension. According to an earlier opinion the cardiac impulse was held to be produced or at least increased by : 4. The recoil that the ventricles are supposed to experience (like a dis- charged firearm) at the instant when the column of blood empties itself into the aorta and the pulmonary artery. The apex would, of course, be driven in the opposite direction by this recoil, that is, downward and a little outward. Landois, however, has pointed out that the blood-column is discharged into the vessels 0.08 second after the beginning of the ventricular contraction, while, on the other hand, the apex-beat begins simultaneously with the first sound. As, however, the apex-beat is observed in bloodless hearts taken from animals after death, and as the apex of the heart is not, as it would be on the theory of the recoil, displaced downward and to the left during systole, but upward and to the right (as has been confirmed by v. Ziemssen in a woman whose heart was exposed), the recoil cannot be regarded as a factor in the problem. After the ventricles by their systolic movement have traced the greatest part of the apex-beat curve, as far as its apex (c), the curve rapidly descends and the ventricles pass from a state of extreme con- traction to one of relaxation. Soon, however, two small elevations appear in the descending limb of the curve at d and e. These are due to the abrupt closure of the semilunar valves, which, being effected with a certain degree of force, is transmitted along the axis of the ventricles as far as the apex, and through the latter even causes concussion of the intercostal space; d corresponds to the closure of the aortic valves, e to that of the pulmonary valves. The valves, therefore, do not close at the same time, there being an interval of about from 0.05 to 0.09 second on the average. Owing to the greater pressure of the blood in the aorta the aortic valves close earlier than those of the pulmonary artery. While investigators are agreed that the first sound of the heart begins at the point b of the cardiogram, various statements have been made with regard to the point at which the registration of the second sound of the heart takes place. Martius designates the depression between c and d (Fig. 28, E) as the point that corresponds to the second heart-sound; Landois the apices d and e, when the tension of the semilunar valves is increased; Hiirthle, Einthoven and Geluk 0.02 second after e; Marey and Fredericq about midway between e and f ; and, finally, Edgren at a point immediately in front of f . Method. In order to determine the time when the heart-sounds are heard, their vibrations are transmitted to a microphone attached to the thorax. The instrument, which is thrown into vibration by each sound of the heart, opens and closes an electric circuit with each vibration and thus attracts an electromagnet, or sets a capillary electrometer (Fig. 229) in motion. If by means of another contrivance the cardiogram is made to register at the same time, the points on the latter at which the heart-sounds are heard can be seen. From the point e to the foot of the curve (at f) comprises the time during which complete diastolic relaxation of the ventricles takes place. 104 TIME-RELATIONS OF THE MOVEMENTS OF THE HEART. THE TIME-RELATIONS OF THE MOVEMENTS OF THE HEART. Method. The time-relations of the individual phases of the movements of the heart can be most reliably discerned in the curves of the apex-beat : When the distance traversed at a uniform rate in a unit of time is known for the registering surface, the time corresponding to each portion of the curve can be ascertained by direct measurement (as in the case of pulse-curves) . Landois determined the time by having the curves traced on a tablet vibrating on the arm of a large tuning-fork (Fig. 60) . The curve then contains in all of its segments small undulations due to the vibrations of the tuning-fork. In Fig. 28, D and E represent apex-beat curves of healthy students registered in this way (in D the elevation d is not distinct). A complete vibration of the tuning-fork (from the apex of one undulation to that of the next) corresponds to 0.01613 second; by counting the number of undulations and multiplying by the factor the time is obtained. Although there is a certain regularity in the time of the individual phases of the movement, the readings nevertheless vary between wide limits even in healthy individuals. The value of a b, which is equivalent to the pause plus the auricular contraction, is subject to the widest variations and depends chiefly on the frequency of the pulse ; for, the more rapidly the heart-beats follow one another, the shorter, naturally, will be the pause, until it finally disappears altogether. Even when the rate of the heart is slow, it is often impossible to distinguish in the curve the portion corresponding to the pause, which, owing to the gradual filling of the heart and the resulting slight bulging of the intercostal space, has a gently ascending form, from that due to the auricular contraction and appearing as a hillock. In one case in which the heart-beats were 55 in a minute, Landois found the pause to be 0.4 second and the auricular contrac- tion 0.177 second. In Fig. 28, A, the pause plus the auricular con- traction, when the heart beats 74 times in a minute, is found on measurement to be 0.5 second. In D the corresponding period a b is equivalent to from 19 to 20 vibrations, or 0.32 second; in E the period is equivalent to 26 vibrations, corresponding to 0.42 second. The ventricular systole is estimated from b, the beginning of the contraction, to e, the completed closure of the semilunar valves of the pulmonary artery. It, therefore, extends from the first to the second heart-sound. This period is also variable, though considerably more constant. When the action of the heart is accelerated, the period becomes less, when the action is slower the period increases; in E it is 0.32 second, in D 0.29 second; when the heart-beats were only 55 Lan- dois found it to be 0.34 second; but when the frequency is exceedingly great it declines to 0.199 second. Landois was able to ascertain the interesting fact that when the left ventricle is enormously hypertrophied and dilated, the duration of the ventricular contrac- tion does not materially exceed the normal. That the ventricle contracts more slowly when the action of the heart is weakened is shown when the registering instrument is placed on the ventricle of an animal that has been killed, and the heart-beat is recorded. In Fig. 30, from the ventricle of a rabbit the slow heart-beats (B) are at the same time of longer duration. This affords an opportunity to determine accurately the length of the period to be allowed for the ventricular systole. Landois thought it wise, in order to avoid misunderstanding, to distinguish the following three separate factors: 1. The interval between the two heart-sounds, that is, from the beginning of the first to the end of the second sound (Fig. 2 8 , b e) . 2. The time occupied by the blood in entering the aorta: This evidently ter- minates at the depression between c and d (Fig. 28, E) ; its beginning, however, TIME-RELATIONS OF THE MOVEMENTS OF THE HEART. 105 does not coincide with b, as from 0.085 to -73 to 0.06 second elapses between the beginning of the ventricular contraction and the opening of the semilunar valves of the aorta. According to this calculation the entrance of the blood into the aorta (aortic inflow) would occupy from 0.08 to 0.09 second. Landois arrived at this result by the following calculation: The interval between the first sound of the heart and the pulse at the axillary artery is 0.137 second. The propagation of the pulse-wave along the distance from the root of the aorta to the axillary artery, which is equivalent to 30 centimeters, cannot occupy more than 0.052 second of this time (corresponding to the analogous velocity in the distance -50 cm. from the axillary to the radial artery = 0.087). Hence, the pulse-wave in the aorta cannot take place earlier than 0.137 minus 0-052 =0.085 second after the beginning of the first sound of the heart. Landois found in agreement with Hurthle that in some cardiograms the point that marks the beginning of the flow of blood into the arteries, or, what is the same thing, the time of the opening of the semilunar valves, is indicated in the ascending limb by a small interval between b and c. The current in the pulmonary artery is not interrupted until the point e is reached. 3. Finally, the time occupied by the muscular contraction of the ventricle may be considered. The contraction begins at b, reaches its greatest degree at c, and is not followed by complete relaxation until f is reached. The apex of the curve c may, however, be higher or lower, according as the intercostal space yields more or less; the position of c is, therefore, variable. The time that elapses between d and e, that is, between complete closure of the semilunar valves and of the pulmonary artery, is greater in proportion as the pressure within the aorta exceeds that within the FIG. 30. Contraction-curves from the Ventricle of a Rabbit Registered on a Plate Attached to a Vibrating Tuning- fork (one vibration m 0.01613 second): A, soon after death; B, taken while the ventricle was in process of dying. pulmonary artery, as the closure of the valves is effected by the pres- sure from above. This interval may vary from 0.05 second to more than twice that length of time; in the latter event the second sound of the heart is also duplicated. If, however, the tension in the aortic system diminishes and the pressure in the pulmonary artery rises, the interval between d and e may be diminished to such a degree that the two coincide at one point in the curve. The time occupied by the ventricles in relaxing (e f ) after closure of the pulmonary valves is also subject to a certain degree of variation; in healthy adults the average may be given as o.i second. When the action of the heart is greatly accelerated, the time occupied by the pause is the first to become shortened, as Bonders and Landois have found; then the time occupied by the auricular and ventricular systole also is shortened, in lesser degree, though quite distinctly. With the highest degree of pulse-frequency the beginning of the auricular systole coincides with the closure of the arterial valves of the preceding heart-beat, a phenomenon that is strikingly illustrated in the tracing from a dog (Fig. 28, C). As during the registration of apex-beat curves the heart is separated from the registering instrument by the soft parts of the intercostal space, which vary in thickness and in resistance and cannot in every case follow the movements of the heart with entire ease, it cannot be expected that the various portions of the curve shall coincide with mathematical accuracy with the corresponding phases of the heart's movements. io6 TIME-RELATIONS OF THE MOVEMENTS OF THE HEART. Gibson had the opportunity of taking cardiograms from a case of fissure of the sternum in a man, and obta'ined the following: time-values: Auricular contrac- tion (a b) =0.115, ventricular contraction (b d) =0.28, interval between the closure of the valves (d e) = 0.09, ventricular diastole (e f) = o.u, pause = 0.45 second. In large mammals (horses) Marey and Chauveau, in 1861, by a most thorough method obtained records of the phases of the movements of the heart in the following manner: Long catheter-like tubes, provided at their lower ex- tremity with a closed and compressible rubber bulb, were connected by means of a flexible piece of tubing attached to the other end with the registering drum of the cardiograph (Fig. 44, KS). It is evident that with every compression of the Aorta. Apex of the Heart. FIG. 31. Curves Showing the Movements of the Separate Portions of the Heart (Chauveau and Marey). rubber bulb the stylus connected with the registering drum of the instrument will be elevated. Fig. 31 shows a number of curves: In making A the rubber bulb was in the right auricle, having been introduced through the jugular vein and the superior vena cava; in making B the bulb was introduced into the right ventricle through the tricuspid orifice; in making D it was introduced through the carotid as far as the root of the aorta; in making C, through the semilunar valves of the aorta into the left ventricle; and, finally, in making E the bulb was applied externally to the apex of the heart between this and the inner aspect of the chest-wall. In all of the curves v indicates the auricular contraction, V the ventricular contrac- tion, s the closure of the semilunar valves (which occurred earlier in B than in C), and P the pause. As the recording surface moves at a uniform rate and the PATHOLOGICAL VARIATIONS IN THE HEART-BEAT. 107 scale for the distance covered in each second is given, the individual periods of time can be measured. It seems probable, however, that the introduction of the tubes into the heart is not without influence on the regular, undisturbed course of its activity. In order to determine the conditions present coincidently with the pressure in the ventricle and in the aorta in the dog, Hiirthle employed his blood-pressure recorders (Fig. 67), which were connected by means of tubes with the interior of the ventricle and of the aorta. A cardiogram was taken at the same time. The vertical lines o, i, 2, 3 indicate conditions identical in time in the three curves. The point o corresponds with the beginning of the ventricular contraction and the first sound of the heart ; while the entrance of the blood into the aorta occurs after an interval, namely at the point i. The points 2 and 3, according to Hiirthle, indicate the closure of the semilunar valves (second sound of the heart). Fred- ericq obtained similar results by means of other experiments. One point remains to be cleared up, namely, whether the auricle and the ventricle work in exact alternation, in such a way that the auricle relaxes at the instant when the ventricle begins to contract, or whether the ventricle begins to Cardiogram. Aorta > Time-Recorder. Ventricle FIG. 32. Simultaneous Record Showing Cardiogram, the Curve of the Ventricular Pressure and that of the Aortic Pressure, from the Dog. Each division of the time-curve = o.oi second (K. Hiirthle). contract while the auricle still remains contracted for a short time, so that for a short period of time at least the entire heart is contracted. Heart-beat curves taken from human subjects appear to show that the ventricular contraction begins as the auricular contraction ends; v. Ziemssen and Ter Gregorianz, who made curves directly from the auricle of the exposed heart of a woman, are likewise in accord with the view that the auricular contraction continues for a time while the ventricles are beginning to contract; and also Heigl, on the strength of a similar observation. A. Fick, who believes that the contractions alternate, considers this alternation as a means for maintaining the pressure in the large venous trunks approximately constant. As the auricle relaxes at the instant when the ventricular systole begins, there is no impediment to the flow of venous blood into the auricle; whereas if the auricular contraction were to persist, the blood would be dammed back. As, further, the auricle contracts at the instant of ventricular relaxation, there will be no abnormal pressure in the veins. In this way the pressure within the auricle may remain more uniform and the blood-stream in the ends of the veins more constant. PATHOLOGICAL VARIATIONS IN THE HEART-BEAT. The position of the heart-beat is altered: (i) By the accumulation of fluid ^serum, pus or blood) or of gases in one pleural cavity. Copious effusions into the pleural cavity, which at the same time compress the lung and force it upward, may displace the heart as far as the right nipple. Effusions into the right pleura cause displacement of the heart to the left. As the right heart is forced IO8 PATHOLOGICAL VARIATIONS IN THE HEART-BEAT. to greater exertion in order to propel the blood through the compressed lung, the apex-beat under such circumstances is usually accentuated. Marked disten- tion of the lungs (emphysema), which depresses the diaphragm, also causes down- ward and inward displacement of the apex-beat. Conversely, elevation of the diaphragm, as a result of contraction of the lungs or of pressure by the abdominal organs, has the effect of displacing the apex-beat upward sometimes as far as the third intercostal space and a little to the left. Thickening of the muscular wall of the heart with dilatation of the cavities (hypertrophy and dilatation) , when it affects the left ventricle, causes an increase in the length and breadth of the chamber, and the accentuated apex-beat becomes palpable to the left of the nipple-line, sometimes in the axillary line in the sixth, seventh, or even eighth intercostal space. Hypertrophy and dilatation of the right ventricle cause an increase in the width of the heart: the apex-beat is felt further to the right, sometimes even to the right of the sternum, but at the same time also a certain distance beyond the left nipple-line. In the rare cases of transposition of the viscera, in which the heart is situated in the right half of the thorax , the apex-beat is of course found in exactly the corresponding situation on the right side of the thorax. Landois was the first to take an apex-beat curve from a heart of this kind and found that it presented all of the normal features. When the heart-beat extends to the left beyond the nipple-line or to the right beyond the parasternal line, the area of cardiac impulse is enlarged transversely, a condition that always indicates hypertrophy of the heart. When this transverse enlargement is unusu- ally great, the apex-beat may extend over several intercostal spaces or over both sides of the thorax. The apex-beat appears abnormally weak in association with atrophy and degeneration of the heart-muscle, or when the innervation of the controlling nerves is impaired. The cardiac impulse may be weakened or even completely obliterated also when the heart is forced away from the chest-wall by an accumulation of fluid or of gas in the pericardium, by a greatly distended left lung, or by an effusion into the left pleural cavity. The same condition results either when the left ventricle is imperfectly filled during contraction (in consequence of marked stenosis of the mitral orifice) or when, owing to extreme narrowing of the aortic orifice, it can empty itself but gradually and slowly. An increase of the apex-beat is observed in the presence of hypertrophy of the walls of the heart, as well as in association with the most diverse irritative conditions (psychic, inflammatory, febrile, toxic) affecting the heart and its con- trolling nerves.' Extreme hypertrophy of the left ventricle causes a heaving apex- beat, so that a portion of the chest-wall is elevated, with systolic concussion. In some cases the apex-beat is quite distinct or even abnormally distinct, while the pulse is quite small. This phenomenon is due to insufficient emptying of the ventricles (spurious contraction of the heart) . Systolic retraction is not infrequently observed on the anterior chest -wall in the third and fourth intercostal spaces on the left side under normal conditions, especially when the action of the heart is accentuated and when there is excentric hypertrophy of the ventricles. As the apex is somewhat displaced with each ventricular contraction and the ventricles at the same time diminish in size, the yielding soft parts of the intercostal space are drawn in to fill the vacuum thus formed. When the heart is adherent to the pericardium and the surrounding connective tissue, movement of the heart during systole becomes impossible and the apex-beat is replaced by systolic retraction of the apical area. Under such circumstances the chest-wall bulges during diastole, in a measure representing a kind of diastolic apex-beat. The changes in the apex-beat that occur in association with functional dis- orders of the heart are best studied by tracing apex-beat curves, as has been done by a number of clinicians since Landois first published his method in 1876. In the curve shown in Fig. 33, P, in reduced size and obtained from a case of marked hypertrophy and dilatation of the left ventricle, the ventricular contrac- tion as a rule is exceedingly large (b c) , although the time occupied in contraction by the greatly increased muscular mass of the ventricular wall is not materially longer than under normal conditions. The curves P and Q were obtained from a man with a high grade of excentric hypertrophy of the left ventricle, resulting from insufficiency of the semilunar valves of the aorta. The curve Q was taken purposely at a point near the epigastrium where systolic retraction was present. Although the position of the individual portions of the curve is changed, the individual phases of the heart's action are nevertheless well shown. PATHOLOGICAL VARIATIONS IN THE HEART-BEAT. 109 Fig. E represents the apex-beat in a case of stenosis of the aortic orifice. The auricular contraction (a b) is quite brief, the ventricular contraction is visibly prolonged and after a short rise (b c) exhibits a series of indentations (c e) caused by the mass of blood forcing its way through the stenotic and roughened entrance to the aorta. Fig. F represents the apex-beat in a case of insufficiency of the mitral valve; a b is well marked in consequence of the increased activity of the left ventricle; the shock (d) caused by the closure of the aortic valves is slight on account of the diminished tension in the arterial system. On the other hand, the shock of the accentuated pulmonic second sound (e) stands like a huge accent high upon the summit of the curve. In consequence of the tension in the pulmonary artery FIG. 33. Various Forms of Pathological Apex-beat Curves. In all of these curves a b indicates the auricular contraction; b c, the ventricular contraction; d, the close of the aortic semilunar valves; e, that of the pul- monary valves; e f, the time occupied by the relaxation of the ventricles. the pulmonary second sound may be so accentuated and it may follow so quickly after the second aortic sound (d) that the two almost or quite coincide (H and K) . The curve in a case of stenosis of the left auriculo-ventricular orifice (G) presents first of all a long, irregular, indented auricular contraction (a b) , due to the fact that the blood is forced through the narrow orifice with considerable agitation and friction. The ventricular contraction (b c) is feeble on account of the imperfect filling of the left chamber. The closures of the two valves d and e are separated by a comparatively long interval and the ear distinctly hears a duplicated second heart-sound. The aortic valves close rapidly because the aorta receives only a small amount of blood, while the more abundant flow of blood into the pulmonary artery causes retarded closure of the pulmonary valves. When the heart-beats are rapid and weak and the tension in the aorta and the pulmonary artery is low, the signs of closure of the valves in the latter 110 THE HEART-SOUNDS. may be entirely obliterated, as in curve L taken from a girl with exophthalmic goiter who suffered from nervous palpitation of the heart. In rare cases of mitral insufficiency a condition in which the right ventricle is greatly overfilled with blood, while the left contains but little, so that the right has to work harder to empty itself than does the left a peculiar action of the heart has been observed, both ventricles appearing at times to contract together and then again the right ventricle alone (Fig. M after Malbranc) . Curve I , which appears in every respect like a normal apex-beat curve, was taken when the entire heart was active; there was present an arterial pulse corresponding to this apex- beat. Curve II, on the other hand, appears to have been recorded by the right heart alone, and it accordingly lacks the closure of the aortic valves (d) ; nor was there an arterial pulse corresponding to this contraction. With respect to the cases just considered Landois expressed the opinion as early as 1879 that the phenomenon could not be explained on the mere supposition that the right ventricle alone is active during the phases in question, without any parallel action on the part of the left. He regarded such a condition as impossible, if for no other reason because of the common arrangement of the muscles in the two ventricles and their equally common innervation. The period of apparent rest of the left ventricle is probably no more than a period of exceedingly feeble action, not strong enough to record itself in the apex-beat curve by the closure of the aortic valves and by a pulse in the arteries. This supposition has in fact been confirmed by Riegel and Lachmann, Eger, Eichhorst, Stern, H. E. Hering, and others. THE HEART-SOUNDS. On listening over the region of the heart, either directly with the ear applied to the thorax, or with the aid of the stethoscope, or in ani- mals to the exposed heart, two sounds are audible that really do not deserve the name of tones, but which in contradistinction from pathologi- cal heart-murmurs are designated heart-sounds. As they possess a cer- tain tonal color, it has been possible to determine their musical pitch. The first sound of the heart is somewhat duller, longer, and lower in pitch by a third or fourth, fluctuating between d sharp and g, not clearly denned, especially at the beginning, and synchronous with the ventricular systole. The second sound of the heart is clearer, more valvular, shorter, and therefore more distinctly marked, varying between f sharp and b flat, clearly defined, and synchronous with the closure of the semilunar valves. The first sound is separated from the second by a short interval, and the second sound from the succeeding first sound by a longer interval. In musical parlance the first sound appears as a rising beat to the second, which is then followed by the pause. The vibration-values and the rhythm may accordingly be expressed as follows : Y Bu - tup (lub-dup) Bu'- tup (lub-dup) The first sound is caused by two factors. As it is heard, though faintly, in excised hearts in which the auriculo- ventricular valves are prevented from being stretched and relaxed, and as it is heard also when the movement and closure of the valves are prevented by means of a finger introduced into the auriculo- ventricular orifice, the principal cause of the sound is to be sought in the muscular murmur, produced by the contracting muscular fibers of the ventricles. THE HEART-SOUNDS. Ill The sound is augmented and reinforced by the tension and vibra- tions of the auriculo-ventricular valves and their tendinous bands at the instant of ventricular contraction. Wintrich, in 1873, succeeded by the use of suitable resonators in dis- tinguishing one sound from the other; the clearer and shorter valvular sound from the deeper and more protracted muscular tone. FIG. 34. Topography of the Thorax and of the Thoracic Viscera: a. d., right auricle; o. s., left auricle; v. d., right ventricle; I, left ventricle with I t apex of the heart; A, aorta; II, pulmonary artery; C, superior vena cava; L L, boundaries of the lungs; P P, boundaries of the parietal pleura (v. Luschka and v. Dusch). Under pathological conditions, such as typhoid fever and fatty heart, in which the heart-muscle is greatly enfeebled, the first sound of the heart may be inaudible. In the presence of insufficiency of the aortic valves, when, owing to the regurgita- tion of the blood from the aorta into the ventricle, the mitral valve is made tense gradually and before the ventricular systole begins, the first sound of the heart is also not infrequently absent. Both of these pathological instances prove that the cooperation of muscle-tone and valve-tone is required for the production of the first sound of the heart and that when one of these elements is lost the heart- sound may become inaudible. It should further be mentioned that the vibra- tions of the semilunar valves before or during their closure and the vibrations of the fluid elements of the blood itself have been adduced as contributory factors in the explanation of the first sound of the heart. 112 ABNORMALITIES OF THE HEART-BEAT. The cause of the second sound of the heart, according to the gener- ally accepted view, is the abrupt closure of the semilunar valves. It is, therefore, said to be chiefly a valvular sound. It is, however, in part due also to a sudden concussion of the fluid particles in the large arterial vessels. Landois has shown from apex-beat curves taken from healthy in- dividuals that the semilunar valves of the aorta and those of the pul- monary artery do not close at the same time. As a rule, however, the difference in time is so slight that the two sets of valves generate only one sound. On the other hand, if, owing to increase of the difference in pressure in the aorta and in the pulmonary artery, this interval be- comes greater, a duplication or splitting of the second sound may become quite perceptible. This may occur in perfectly healthy individuals, especially at the end of inspiration or at the beginning of expiration. It is important to remember, however, that although the second sound corresponds with the closure of the semilunar valves, it appears proved that the closure itself gives rise to no sound ; it is only an instant later, when the tension of the valves becomes greater, that the second sound becomes audible. It is generally believed that the points on the chest-wall at which the heart- sounds are heard most distinctly on auscultation correspond to the points in the neighborhood of which they are produced. The first valvular sound produced at the right auriculo-ventricular orifice is heard most distinctly at the junction of the fifth rib with the sternum on the right side, and is transmitted from that point somewhat inward and obliquely upward along the sternum (Fig. 34, i). As the left auriculo-ventricular orifice is directed more posteriorly, toward the interior of the thorax, and is covered in front by the arterial orifices, the first mitral valvular sound is heard best at the apex or immediately above it, where a strip of the left auricle is in immediate contact with the chest-wall (1^ I) . As the orifices of the aorta and pulmonary artery are so close together, it is advisable to listen for the aortic second heart- sound in the prolongation of the axis of the aorta, that is, at the right border of the sternum, at the inner extremity of the right costal cartilage (at 2). The pulmonic second heart-sound is heard most distinctly in the second left intercostal space a little to the left and beyond the edge of the sternum (at II). The aortic second sound is clearer, sharper, and shorter, and is heard over a larger area than the pulmonic second sound. To determine the intensity of the heart-sounds quantitatively H. Vierordt inserts between the chest-wall and the ear a series of solid rubber plugs, which are poor conductors of sound, placed one upon the other in the form of a column. ABNORMALITIES IN THE HEART-BEAT. Accentuation of the first sound of the heart in both ventricles indicates a more powerful contraction of the ventricular muscle and a consequent, sudden, and increased tension of the auriculo-ventricular valves. Accentuation of the second sound is a sign of increased tension in the interior of the corresponding large vessels. Hence accentuation of the pulmonic second sound, which is such an important diagnostic sign, always indicates hyperemia and excessive tension in the lesser circulation. Feeble heart-sounds are caused by sluggish, weakened heart-action or abnormal ischemia; they are observed particularly in cases of morbid degeneration of the heart-muscle. The cause of weakness of individual heart-sounds can be deduced from the foregoing explanation. The term embryocardia is used when the two sounds of the heart are exactly alike with respect to strength and the intervals between heart-beats, resembling the ticking of a clock; the phenomenon indicates weakening of the heart-muscle. Irregularities in the structure of individual valves may render the heart- sounds impure by causing irregular vibrations. When pathological cavities filled with air are present in the immediate neighborhood of the heart, they may act as DURATION OF THE MOVEMENT OF THE HEART. 113 resonators and reinforce the heart-sounds, so that the latter often assume a metallic, ringing character. Both the first and the second heart-sound may be duplicated or split. Duplication of the first sound of the heart is explained by failure of the tricuspid and mitral valves to contract at the same time. Some- times a sound may be heard that is caused by the contraction of a well-developed auricle and precedes the first sound like a presystolic murmur. As the closure of the aortic valves does not coincide exactly with that of the pulmonary valves, duplication or splitting of the second sound merely represents an exaggeration of physiological conditions. All factors that cause acceleration in the closure of the aortic valves such as ischemia of the left ventricle and retardation in the closure of the pulmonary valves such as the presence of an excessive quantity of blood in the right ventricle, and both' factors together when there is stenosis of the left auriculo- ventricular orifice favor duplication of the second sound. When the valves of the heart are the seat of irregularities in association with either stenosis or insufficiency, throwing the blood-stream into eddies or oscilla- tions or producing friction, the heart-sounds are replaced by murmurs, that is, sounds produced by the fluids and always associated with "circulatory disturb- ances and the valvular changes referred to. It is rare for deposits and new-growths projecting into the ventricle to give rise to murmurs in the absence of valvular lesions or circulatory disturbances. Heart-murmurs are always associated with the systole or diastole. As a rule, systolic murmurs are louder and more accentu- ated than diastolic. Sometimes they are so loud that even the thorax is thrown into vibration purring tremor. Diastolic murmurs always depend on structural changes in the mechanism of the heart, such as insufficiency of the arterial valves or stenosis of the venous orifices (usually on the left side only). Systolic murmurs are not always due to disturbances of the cardiac mechanism. In the left heart systolic murmurs may be caused by insufficiency of the mitral valve, stenosis at the aortic orifice and by calcification or abnormal dilatation affecting the ascending aorta. Systolic murmurs in the right heart, which are much more rare, are due to insufficiency of the tricuspid valve or stenosis at the pulmonary orifice. Systolic murmurs are often present, although never so loud, in cases without any valvular lesion, being caused by abnormal vibration of the valves or of the walls of the arteries. They are heard most frequently at the pulmonary orifice, next at the mitral, and more rarely at the aortic and tricuspid orifices. Anemia and acute febrile affections are the causes of these murmurs. Heart-murmurs are sometimes produced by the friction of opposed roughened surfaces of the inflamed pericardium (friction-murmurs) . The friction-sound may be both audible and palpable. DURATION OF THE MOVEMENT OF THE HEART. The excised heart continues to beat independently for a time: in cold-blooded animals for a long period, even for days, in warm- blooded animals for a much shorter time. The last vestige of cardiac action has, however, been observed in the rabbit after 15^ hours, in the mouse after 46^ hours, in the dog after 96^ hours, and in a three-months- old human embryo after 4 hours. The contraction of the excised heart may be reinforced and accelerated by irritation. The contraction of the ventricle first becomes enfeebled, and it is further observed that the contraction of the auricle is not always followed by a ventricular systole, two or more auricular contractions being succeeded by only one feebler ventricular movement. The contractions of the ventricles, in addition to being more infrequent, require a longer time for their completion, and give the impression of being labored and sluggish (Fig. 30). Later, the ventricles cease to contract altogether and only the auricles continue to beat feebly. Direct irritation of the ventricles, however, as by a prick, is followed by a single contraction. Still later the left auricle ceases while the right auricle continues to beat, and it is the right auricular appendage that continues to beat the longest, being accord- ingly known to the ancients as "ultimum moriens." The same obser- 8 114 THE CARDIAC NERVES. vation has been made in executed criminals. In the opened heart the papillary muscles fail to contract synchronously with the auricular wall after from two to three minutes. Engelmann made the interesting observation that the muscles of the auricle may lose their power of contracting, in response to irritation of the vagus or as a result of immer- sion and swelling in water, without losing the power of conducting stimuli. An analogous phenomenon has been observed- with respect to the nerves. After the heart has ceased beating altogether, it can be temporarily roused by direct stimulation, especially by heat; and again the auricles and auricular appendages are the last to react. As a rule, when the heart has been temporarily stimulated to greater activity it ceases to beat the earlier; before the orderly succession of beats ceases altogether tremu- lous, "undulating" movement of the muscle-bundles usually takes place. In mammals, when the irritability of the heart has ceased, it can be temporarily restored by injecting arterial blood into the coronary vessels. In the frog the heart, which at first becomes rigid, may be revived by filling its cavities with fresh blood. As the heart uses up oxygen and eliminates carbon dioxid, it is quite conceivable that it should beat longer in oxygen than in nitrogen, hydrogen, carbon dioxid, hydrogen sulphid or in a vacuum, even when, to avoid desiccation, aqueous vapor is generated in the vacuum. When the heart, after it has ceased to beat, is returned to a medium containing oxygen, it begins to beat again. THE CARDIAC NERVES. The cardiac plexus is formed by : i . The cardiac branches of the trunk of the vagus nerve ; these include cardiac branches from the external branch of the supe- rior laryngeal nerve, the inferior laryngeal nerve, and sometimes the pulmonary branches of the vagus, in larger number on the right than on the left side. 2. The superior, middle, inferior, and lowest cardiac branches from the three cervical ganglia and the first thoracic ganglion of the sympathetic nerve, which frequently vary in number and in size (sometimes one of the branches accompanies the descending branch of the hypoglossus for a part of its course) . The branches of the plexus are the deep and the superficial nerves; the latter usually contain a ganglion at the bifurcation of the pulmonary artery beneath the arch of the aorta. The following structures are regarded as belonging to the cardiac plexus: (a) The right and left coronary plexuses, which convey the vasomotor nerves of the coronary vessels through the vagus portion and the dilators through the sympathetic; and in addition contain sensory fibers derived from the vagus and passing principally to the pericardium. In patients suffering from disease of the heart the presence of sensory nerves is indicated by the occurrence of constant or paroxysmal pain. In the frog, reflex phenomena may be induced from the ventricle in the various portions of the heart, and they probably have their reflex center in the medulla oblongata. (6) The nerves embedded in the heart-muscle and in the furrows, which are richly supplied with ganglia and which have been designated the automatic motor centers of the heart. The heart contains a circle of nerves richly supplied with ganglia at the edge of the interauricular septum and another at the junction of the auricles and the ventricles. Wherever the two meet they exchange fibers. The ganglia are for the most part found near the pericardium. In mammals the two larger ganglia are situated close to the orifice of the superior vena cava; in birds the largest node of nerve-tissue, containing thousands of ganglia, occupies the posterior point of decussation of the longitudinal and transverse sulci. These nodes of nerve-tissue send smaller branches into the muscular walls of the auricles and ventricles, and these branches in turn are the seat of smaller ganglia. In the frog a large collection of ganglia, Remak's ganglion, is situated, together with the vagus fibers, within the wall of the sinus of the vena cava (the dilated orifice of the venag cavas in the right auricle whose independent movement pre- IRRITABILITY OF THE AUTOMATIC MOTOR CENTERS. 115 cedes that of the auricles). From this ganglion the vagus fibers pass as the anterior and posterior septal nerves, each of which is provided with a ganglion at the auriculo-ventricular junction, the ventricular ganglion, or Bidder's ganglion. The nerve-fibers, which are for the most part non-medullated, can be traced further in connection with the ganglia. The motor fibers terminate with slightly clubbed extremities in each muscle- cell; the sensory, which are derived from medullated fibers, in flat, expanded terminal plexuses, which are quite abundant in the endocardium and the peri- cardium. All ganglion-cells are bipolar or multipolar. In the frog most of them are surrounded by a network of fibers; in Bidder's ganglion spindle-shaped cells with two processes, one at each extremity, predominate. In the rabbit and in the frog the ganglion-cells belonging to the sympathetic system have two nuclei, while the vagus ganglia have only one. After division of the vagus branches (in the frog) the spiral process and the pericellular network from which it originates undergo degeneration. The straight process gives off the muscle-nerves. The bulb of the aorta contains numerous nerves for its muscle-fibers; but whether it contains ganglia also is doubtful. IRRITABILITY OF THE AUTOMATIC MOTOR CENTERS IN THE HEART AND IN THE HEART-MUSCLE. There are at the present time only two theories with regard to the irritability of the heart and its spontaneous rhythmic action. 1. The older theory teaches that the "automatic centers" that excite the movements and maintain an orderly rhythm are situated within the heart and that this function resides in the ganglia. 2. It is assumed that not one but several such centers are present in the heart and are connected with one another by conducting paths. So long as the heart is intact the various centers are stimulated to rhythmic activity in a definite order from the principal center, the impulse being conveyed through the conducting paths from that center. The forces that excite these regular continuous movements are not known. If, however, diffuse stimuli, of which the simplest is a strong electrical current, are applied to the heart, all of the centers are thrown into action and a spasmodic contraction of the heart takes place without any rhythm of movement. The dominating center is situated in the auri- cles (in the frog), whence, therefore, the regular progressive movements usually proceed. When its irritability is reduced, as by applying opium to the septum with a cotton pledget, a different set of centers appears to gain control, and the movement may then be propagated from the ventricles to the auricles. 3. The nerve-centers of the auricles are more irritable than those of the ventricles; hence they continue to beat independently for a longer time when the heart is left to itself. 4. All stimuli of moderate strength acting directly on the heart cause primarily an increase in the rhythmic heart-beats; stronger stimuli cause, in a short while, diminution progressing to paralysis, often pre- ceded by spasmodic tremulous "undulation or flickering." Increased activity on the part of the heart exhausts its strength the more rapidly. 5. Individual weak stimuli, such as are insufficient to exert any effect on the heart, may be rendered efficient by repetition, as the heart is capable of summation of the individual stimuli. 6. Even the feeblest stimuli that are at all capable of exciting a contraction always excite an active contraction, that is, "the minimal stimulus has a maximal effect." Il6 IRRITABILITY OF THE AUTOMATIC MOTOR CENTERS. 7. Each contraction of the heart is followed by a short period during which the heart is less susceptible to subsequent stimuli (Marey's re- fractory period) and the conducting-power of the muscle-substance is reduced. 8. Stimulation of the heart-centers, apparently reflex, takes place on the inner surface of the heart. Feeble stimuli from this surface are more effective in accelerating and exciting the action of the heart than stimuli from the external surface of the heart. Stronger stimuli, which cause arrest of the heart, also act more readily from the internal than from the external surface of the heart; under such conditions also the ventricular portion is always first to be paralyzed. 9. Portions of the heart that are devoid of ganglia are incapable of independent movement unless a stimulus be applied ; they contract only once to a single direct stimulus, or they may beat rhythmically if the stimuli are applied continuously. Such a stimulus may be provided by the continuous pressure of fluid within the cavities of the heart or by means of chemical agents brought in contact with the heart. 10. The pulsations of stimulated portions of the heart devoid of ganglia indicate that the ganglia are not absolutely necessary for the production of rhythmic contractions ; but the ganglia are more irritable than the muscle itself. They control also the regular alternating action of the various portions of the heart, so that normal cardiac action must be regarded as under the control of the ganglia. 11. If the heart be cut in such a way that the individual pieces remain in communication, the regular contractions beginning in the auricles and propagated in peristaltic or undulating movements to the ventricles persist for some time. When, however, the heart is completely divided into two pieces, auricle and ventricle, the movements of both continue separately naturally, no longer in orderly succession, but quite independently. The principal experiments on which the foregoing propositions are based are as follows: Experimental Division and Ligation of the Heart. These experiments have been performed chiefly on frogs' hearts. Ligation differs from division in the fact that the physiological connection is destroyed by drawing a ligature tightly around the parts and loosening it again, while the anatomical continuity of the heart -wall and the integrity of the cavities of the heart are maintained. i. Stannius' Experiment. After separation in a frog's heart of the sinus of the venae cavae from the auricle, either by incision or by constriction, the heart is arrested in diastole, while the sinus continues to beat independently. If the heart be again divided at the auriculo- ventricular junction, the ventricle, as a rule, begins at once to beat again, while the auricles continue in diastolic arrest. In accordance with the position of the second line of division the auricles may continue to beat in association with the ventricles, or the auricles alone may contract, while the ventricles remain at rest. The experiment has been interpreted in the following manner: The sinus of the venae cavae contains Remak's ganglion, which is remarkable for its extreme irritability, while Bidder's ganglion, which is situated at the auriculo-ventricular junction, possesses a lesser degree of irritability. In the normal heart the latter receives its motor impulses from the former. W nen the sinus of the venae cavse is severed, the stimulating Remak's ganglion is without any influence on the heart. The latter becomes arrested for two reasons: because Bidder's ganglion by itself does not possess .sufficient power to set the heart in motion, and because the division stimulates the inhibitory nerves of the heart (vagus), which are situated at this point. Pulsation can, however, be induced in a heart that has been ar- rested in this way by irritation of Bidder's ganglion, as by gently pricking the auriculo-ventricular junction, or by the passage of a moderately strong constant IRRITABILITY OF' THE AUTOMATIC MOTOR CENTERS. 117 current. In the latter event the ventricular beat sometimes precedes that of the auricles. If, now, the auriculo-ventricular junction be divided, the ventricle begins to pulsate, partly because the procedure stimulates Bidder's ganglion, and partly because the heart is no longer under the influence of the vagus, which had been stimulated by the first division. If the division at the auriculo-ventricular junction is made in such a way as to leave Bidder's ganglion in the auricle, the latter would pulsate and the ventricle remain at rest; if the ganglion is divided into two halves, both the auricles and the ventricles pulsate, because each is stimulated by its own half of the ganglion. 2. When the ventricle alone is divided in the frog's heart by ligature or in- cision at the auriculo-ventricular furrow, the sinus and the auricles continue to beat undisturbed, while the ventricle is arrested in diastole; the ventricle responds to a local irritant with a single contraction. If the incision is made in such a way as to leave the lower edge of the interauricular septum attached to the ventricle, the latter also continues to pulsate. In the case of the rabbit's heart, also, the ventricles continue to pulsate if a small strip of the auricles is preserved, separated from the auricular nerves. 3. Experiments performed by A. Fick in 1874 first showed that the irritative process in the contractile tissue of the frog's heart is propagated in all directions and that the entire frog's heart acts in a measure like a single continuous muscle- fiber. Thus, for example, a transverse incision, involving the ventricle of the frog's heart, does not prevent the appended flap from taking part in the systolic contraction. This is shown also by the following experiments of Engelmann. If the heart is cut into strips, as by zigzag incisions, in such a manner that the individual pieces remain in connection with one another by means of muscle- substance, the strips pulsate in regular succession, in whatever way they may be connected with one another, as a result of the direction of the incisions. The velocity of propagation, under such circumstances, is from ten to thirty millimeters in the second. These experiments also confirm the observation that the continuous stimulus that propagates the contraction is not conducted by nerve-paths but by the substance of the contractile mass. 4. When the apex of the heart has been separated from the rest of the organ by a ligature it ceases to take part in the contraction of the heart, which continues to pulsate; a direct stimulus, such as a stab of the apex, is followed' by only a single contraction. If the heart is filled with saline solution under pressure (both of which act as stimuli) , the apex will continue to pulsate. The same thing is observed after poisoning with delphinin or quinin. If a cannula is tied in the ventricle from a point above the auriculo-ventricular junction to the apex, the latter is likewise arrested; if, however, the apical portion is filled through this cannula with oxygenated blood under steady pressure, the apex will pulsate. The excised apex of the heart resting spontaneously, when stimulated by induction-currents, responds to the weakest efficient stimulation by a maximal contraction; but the application of tetanizing currents is not followed by true tetanus. Closing and opening the constant current applied to the severed apex give rise only to the ordinary closing and opening contractions. 5. When the point of ligation is within the auricles, the pulsations of the heart occur in successive periods (group -f ormation) , and the contractions often increase in strength by regular gradations (stair-case ascent) . 6. When the bulb of the aorta, which is devoid of ganglia, is isolated by con- striction (frog), it continues to pulsate when the internal pressure is moderate; after it has ceased beating, a single stimulus will give rise to a series of renewed contractions. The number of contractions is increased by raising the temperature to 35 C. and by increasing the internal pressure. 7. The isolated venae cavae and their sinuses exhibit normal contractions. If they are still connected with the heart they will control the movements of the heart, that is, contraction of the entire heart may be induced from the position of each of the large veins and the rhythm of the heart may be thus influenced. Conduction takes place only through the muscle-substance and not through the nerves. Porter maintains with regard to the hearts of the dog and the cat that any part of the heart that is excised may continue to pulsate if only it be suffi- ciently nourished. In opposition to the doctrine that has just been expounded, namely that the stimulating influence is sent out by the cardiac ganglia, it may be observed that this theory has recently begun to waver. In view of the Il8 DIRECT STIMULATION OF THE HEART. fact that the embryonal heart, in which it has been impossible to dem- onstrate the presence of ganglia, pulsates like the heart of certain inverte- brates, some recent investigators assert that the automatism of the cardiac action resides in the muscle itself. Similarly, His, Jr., and Romberg, on developmental grounds, teach that the ganglia belong really to the sensory nerves of the heart, and that, therefore, there are no automatic nerve-centers at all. When Krehl and Romberg isolated portions of the rabbit's heart devoid of ganglia by crushing, but in such a way that, so long as the circulation was maintained, they represented anatomical portions of the heart, they found that these pieces continued to pulsate for hours. It is said that even excision of the entire septum of the frog's heart, including Remak's ganglion, has no disturbing effect on the heart-beat. The propagation of the contraction from the auricles to the ventricles is said to take place through the muscle-fibers that pass from the former to the latter. That the conduction of the stimuli from auricle to ven- tricle, which does not take place continuously, but periodically in the same rhythm as the heart-beats, is not transmitted through the nerve- paths is proved by the slow rate at which it is effected, the conduction being 300 times slower than in motor nerves. Engelmann expresses his views upon these questions as follows : The muscle-cells of the heart itself and not a system of nerve-ganglia constitute the excito-motor central organ ; as such they generate the motor stimuli that cause the heart to beat. As those muscle-cells that surround the large veins emptying into the heart are most susceptible to the irritating influence of automatic move- ment, the systolic contraction occurs first at this point, to spread then in a peris- taltic manner successively to the auricles, the ventricles, and the bulb of the aorta. The motor stimulus is propagated directly from muscle-cell to muscle-cell. All of the muscle-cells of the entire heart form together a single physiologically conducting contractile mass. Within each individual portion of the heart-^- venous trunks, venous sinuses, auricles, ventricles, bulb of the aorta the motor stimulus is propagated rapidly, in a manner comparable to the contraction of a striated muscle. Those muscle-cells, on the other hand, that form the connecting bridges between the individual portions of the heart conduct slowly, in a manner comparable to unstriated or embryonal muscles. Consequently every individual portion of the heart contracts practically at the same time as a whole; while, on the other hand, the systole of each portion of the heart situated farther on in the course of the blood-stream can take place only after an actual interval, long enough for the blood to be carried from one part of the heart into the next. As the fibers of the heart-muscle, in the act of contraction, temporarily lose their contractility and conducting power, as a sort of fatigue-phenomenon, they contain within themselves the periodicity of contraction and relaxation systole and dias- tole. A cycle of the entire heart may be induced from any point in the large veins. When the cardiac stimuli succeed one another slowly, each individual car- diac cycle becomes shorter, but more powerful. The blood is then propelled in larger quantities and with greater force; while if the succession is more rapid, less blood is propelled with a lesser degree of force. Direct Stimulation of the Heart. All direct cardiac stimuli act much more vigorously from the internal than from the external surface of the heart. When the stimulation is severe or protracted, the ventricular portion is always paralyzed first. (a) Thermic Stimuli. Descartes had already observed in 1644 that the eel's heart could be made to pulsate more rapidly by the application of heat. Alex. v. Humboldt explained the acceleration of the pulse that takes place in man in a hot medium in the same way. As the temperature continues to rise, the heart- beats at first often reach a considerable frequency. They then become more infrequent again, and finally cease altogether, and the muscle is found to be con- tracted. As a rule, the ventricular portion is arrested before the auricles, some- times after a period of tetanic undulatory spasm. At a temperature of 25 C. and above, the ligated frog's heart immersed in a 0.6 per cent, saline solution, MECHANICAL STIMULI. ELECTRICAL STIMULI. 119 soon becomes arrested, and continues at rest if kept at this temperature. Up to 38 C. Landois has seen it recover if removed quickly. The inner surface of the heart reacts much more readily to all degrees of temperature than the external surface. If the heart, after having been arrested, is removed from the warm bath, it begins to beat rapidly after a pause, which may be interrupted by one or two beats, the frequency gradually diminishing until the normal rate is attained. If the ventricle alone is heated, the frequency of pulsation is not increased. The volume and the extent of the cardiac contractions increase up to a tem- perature of about 20 C., and beyond that point they begin to diminish again. The functional power increases between 8 and 33 C.; but the frequency increases more than the efficiency of the pulsations. The duration of the contraction at 20 C. is only about one -tenth of what it is at 5 C. The heated heart reacts to rapidly intermittent stimuli, the cold heart only when the intervals are of consid- erable length. The mammalian heart ceases to beat at from 44.5 to 45 C. As the heat of the blood diminishes, the heart pulsates more slowly. When a frog's heart is placed on ice between two watch-glasses, its rate diminishes considerably; between 4 C. and o C. the pulsations of the frog's heart cease. When a frog's heart is suddenly removed from warm water and placed on ice, the beat is accelerated; conversely, when it is transferred from ice to warm water, the beat is at first slowed and only after a time accelerated. (b) Mechanical Stimuli. Pressure applied to the outside of the heart causes an acceleration of the cardiac action. In man also light pressure applied to the auriculo-ventricular junction of an exposed heart gave rise to a secondary shorter contraction of both ventricles following each heart-beat. Heavy pressure causes an irregular, undulatory contraction of the muscle, such as may be produced by compressing the excised heart of a warm-blooded animal between the fingers. Increase of the blood-pressure in the interior of the heart effects a similar accelera- tion, and decrease of the pressure a corresponding diminution in the number of heart-beats. When the intracardiac pressure is excessive, the overstimulation results in irregularity or even slowing of the heart-beat. A resting heart that is still irritable will react by a single contraction to a mechanical impulse (prick). (c) Electrical Stimuli. A moderately strong constant current passing continu- ously through the heart produces an increase in its rate. Ziemssen succeeded in accelerating the beat of an exposed heart two-fold or three-fold by passing a strong galvanic current uninterruptedly through the ventricles. Exceedingly strong constant currents, as well as tetanizing faradic currents, produce tetanic undulatory contractions of the heart-muscle, with lowering of the blood-pressure. If the ventricle of the frog's heart has been permanently relaxed by being clamped at the auriculo-ventricular junction, and one electrode of a constant current is applied to the ventricular wall, and the other to any portion of the trunk, systolic contraction of the ventricle takes place when the 'current is closed only if the kathode is placed in contact with the ventricle; conversely when the current is opened only if the anode is in contact with the heart-wall. The feeblest faradic currents accelerate the heart-beat; stronger currents produce irregularities, which may go on to fibrillation. A single induction-impulse applied to the ventricle in systolic contraction has no effect either in the frog or in the mammal. When, however, it is applied to the ventricle in diastolic relaxation, the succeeding systole takes place earlier. The auricles and the apex of the heart, which is devoid of ganglia, but may be excited to activity by suitable stimulation, react in the same way. During their systole an induction-impulse is ineffective, but in diastolic rest the impulse gives rise to a contraction, which is followed by a ventricular contraction. Even strong tetan- izing induction-currents applied to the heart are unable to produce tetanus of the entire musculature. There develop between the electrodes localized, white, cylin- drical elevations, as in the muscles of the intestines, which may persist for several minutes. After severe and continued tetanization the undulatory contractions outlast the stimulus. Also the isolated apex of warm-blooded animals may exhibit this undulatory contraction only so long as the stimulus lasts. The heart of a previously warmed frog, as well as the isolated apex, reacts to electric stimuli by flickering. The fibrillating or flickering rabbit's heart often returns spontaneously to its normal contractions, the dog's heart with greater difficulty. After the contractions of the frog's heart have become weak and irregular, they can be made regular and isochronous with the rhythm of the stimulus by means of elec- tric stimuli applied in rhythmical succession. The feeblest stimuli that are at all efficient act as well in this connection as the strongest; even with the weakest 120 CHEMICAL STIMULI. stimulus the contraction of the heart is the most vigorous possible. Hence, this minimal electrical heart-stimulus is as effective as a maximal stimulus. V. Ziemssen was unable even with strong induction-currents to cause a variation in the rate of the beat of the exposed human heart. The ventricular diastole alone appeared to be no longer complete, and in addition certain minor irregularities were observed in the contractions. By opening and closing or by reversing a strong constant current applied to the heart of a woman, it was possible to increase the number of heart-beats, and the increased number of pulsations cor- responded with the number of the electrical impulses. For example, from a normal of 80 the number of heart-beats was raised to from 120 to 140 to 180 by the application of from 120 to 140 to 180 electrical impulses. Conversely, it was possible also to reduce the normal number of pulsations from 80 to 60 or 50 by applying an equal number of powerful stimuli. In the healthy subject also v. Ziemssen found that he could influence the rhythm and the strength of the heart by applying an electrical current through the chest-wall. (d) Chemical Stimuli. Many chemical agents, particularly when applied in a state of dilution to the inner surface of the heart, increase the number of pulsa- tions, but when applied in concentrated form or when allowed to act for some time diminish the number or paralyze the heart. Bile and biliary salts diminish the number of heart-beats, as does also absorption of the bile into the blood. In dilute solution, however, both accelerate the action of the heart. The same effect is produced by acetic, tartaric, citric and phosphoric acids. Chloroform and ether when applied to the inner surface of the heart have a distinctly retarding or even paralyzing effect; in small amounts ether accelerates the heart-beats. Opium, strychnin, alcohol, and chloral hydrate have an analogous action. Klug caused blood impregnated with various gases to pass through the frog's heart and found that sulphurous acid, chlorin-gas, nitrous-oxid gas, hydrogen sulphid and carbon monoxid acted as heart-poisons. In the same way, blood saturated with carbon dioxid exhausts the heart, which, however, may recover if the carbon dioxid escapes. A deficiency of oxygen produces a grouped rhythm, in the same way as the phenomena of asphyxiation manifest themselves in the respiratory apparatus in grouped movements. Rossbach found that local irritation of a circumscribed area of the frog's ventricle by means of mechanical, chemical, or electrical stimuli during contraction causes immediate relaxation in partial diastole of the part to which the stimulus is applied. The immediate after-effect of this form of irritation is a permanent shrinking of the irritated portion of the heart-fibers, and this is likewise strictly confined to the area of irritation. The shrunken portion ceases to functionate and remains permanently robbed of its vital properties. If the same stimuli are applied during diastole, the irritated portion relaxes earlier than the portion that has not been irritated, and the diastole of the irritated portion lasts longer than that of the non-irritated portion. If the weakest stimuli are allowed to act for a considerable length of time on any part of the frog's ventricle, the irritated portion always relaxes earlier than the non-irritated, and the diastole of the irritated portion lasts longer than that of the non-irritated. Heart- poisons comprise such substances as have a special effect in diminishing or abolishing the movements of the heart. In this respect the neutral salts of potassium are most remarkable. In small doses they accelerate the heart-beat. Yellow potassium ferrocyanid, when injected into a frog's heart, will cause systolic arrest of the ventricles, even when greatly diluted. If blood subsequently enters the ventricle as the result of the contraction of the auricle, the ventricle may again take part in the contraction. Under such conditions, the ventricular muscles sometimes relax in areas after first undergoing reddening. The contraction of the ventricle, which is exceedingly sluggish, later travels from the auriculo- ventricular junction in a peristaltic wave to the apex. The Javanese arrow-poison, antiar, causes systolic arrest of the ventricles, with diastolic arrest of the auricles; mus- carin causes diastolic arrest of the heart, which can be overcome by means of atropin. Some of the heart-poisons in small doses cause slowing and in larger doses not infrequently acceleration of the heart -beat: digitalis (and the toxic substances of oleander and the mayflower, which are similar to it), morphin, and nicotin. Others in small doses cause acceleration and in large doses slowing: veratrin, aconitin, camphor. THE CARDIOPNEUMATIC MOVEMENT. 121 THE CARDIOPNEUMATIC MOVEMENT. As the heart during systole occupies a smaller space in the interior of the thorax than during diastole, air must enter the thorax as the heart contracts if the glottis is open. When, however, the heart relaxes in diastole, air must escape through the open glottis as the heart enlarges. A similar influence must be due to differences in the degree of fulness of the intrathoracic vascular trunks. This cardio pneumatic movement is, in animals in which during hibernation the respiratory movements are suspended, of the greatest importance for the maintenance of metabolism, which continues in moderate degree. The interchange of carbon and oxygen in the lungs is greatly facilitated by agitation of the pulmonary gases, and this interchange suffices to aerate the blood passing slowly through the lungs. Method. The movement may be demonstrated by means of: 1. The manometric flame, the trachea of a curarized animal being opened and connected with a bifurcated tube, one branch of which leads to the gas-tubing and the other to a small gas-flame. As in this manner a free communication is established between the organ of respiration and the gas-supply, the movements of the heart will be transmitted to the gas-flame. In man it is possible, after a little practice, to transmit the movement in an analogous manner to the gas- flame through one nostril after closure of the other nostril and the mouth, or through the mouth after closure of the two nostrils. 2. By acoustic means, namely by introducing an exceedingly sensitive whistle constructed from a hollow sphere, in animals into the trachea divided transversely, in man especially when the heart's action is stimulated into the mouth, after closure of the nose, it is possible to demonstrate the cardiopneumatic movement, particularly if the whistle is blown continuously and with extreme softness. 3. By means of the cardiopneumograph (Fig. 35). This consists of a tube, which is held between the lips (D), while respiration is suspended, the glottis is opened and the nostrils are closed. The extremity of the tube, which is bent upward, perforates a small plate (T) , over which a delicate membrane consisting of a mixture of collodion and castor-oil is stretched with moderate force. From the center of the membrane a glass thread (H) passes over the free edge of the plate and is provided at its extremity with a delicate hair, which registers the movements of the membrane on a tablet (S) moved by clockwork. Every ex- piratory movement of air causes depression and every inspiratory movement elevation of the recording point. Attached to the side of the tube is a valve with a sufficiently large opening (K) and which may be opened to allow the indi- vidual to breathe freely during a pause. The periodic movements of the respiratory gases propelled by the heart-beat cause associated movements in the delicate collodion membrane, and these are in turn transmitted to the recording lever. The graphic curve (Fig. 35, A and B) exhibits the following details: 1 . The respiratory gases undergo a sudden expiratory movement coincidently with the first sound of the heart because at the instant of the ventricular systole the blood from the ventricles has not yet left the thorax, while venous blood is pouring into the right auricle through the venae cavae, and because in the same instant of systole the dilating branches of the pulmonary artery must cause approximately the same quantity of air to escape from the nearest air-passages in the lungs. In fact, the blood contained in the right auricle does not leave the thorax at all; it is only transferred to the lesser circulation. This expiratory movement would often be greater if it were not limited by two factors, namely: (a) because the muscular mass of the ventricle occupies a somewhat smaller vol- ume during contraction, and (6) because the thoracic cavity in the region of the fifth intercostal space is somewhat enlarged outwardly by the apex-beat. 2. There follows immediately a marked inspiratory movement of the respira- tory gases, in consequence of which the large ascending limb of the curve is re- corded. As soon as the blood- wave has advanced from the root of the aorta to those portions of the large arteries that lie at the boundaries of the thoracic cavity, a much larger quantity of arterial blood begins to leave this cavity, because venous blood is at the same time being poured into it through the venae cavae. 122 INFLUENCE OF RESPIRATORY PRESSURE ON THE HEART. This inspiratory movement would also be larger were it not for a slight diminution in the volume of the oral and nasal cavities, attended with an expiratory move- ment that takes place at the same time on account of the filling of its arteries oral pulse, nasal pulse. 3. After the second sound of the heart (at 2), which at times causes a slight depression at the apex of the curve, the blood is dammed back in the thorax, in correspondence with the retrograde wave. As a result a second expiratory movement manifests itself in the descending portion of the curve. 4. The subsequent secondary wave-movement of the blood from the heart immediately again causes an inspiratory movement of gases, which produces the recoil elevation in the arteries of the body. 5. More blood now begins to flow into the thorax through the veins with slight fluctuations, and the next heart -beat takes place. FIG. 35. Landois' Cardiopneumograph, and Cardiopneumatic Curves Obtained with its Aid. A and B, from man; i and 2 correspond to the period of the first and second heart-sounds; C, curves from the dog; D, showing the instrument in use- Pathological. In the healthy human subject a crepitating sound is not rarely heard close to the heart, resulting from the movement of the air in the lungs, brought about by the movement of the heart. If there are near the heart abnor- mally narrow places in the bronchi, through which the respiratory gases are forced, so that they generate a sound or murmur, a fairly loud, sibilant or whistling murmur, known as the pathological Cardiopneumatic murmur, is heard in rare cases. In the presence of cardiac lesions characterized by considerable fluctuations in the quantity of blood in the vessels of the lesser circulation, the cardiopneumatic movement must be quite marked, as, for example, in cases of insufficiency of the pulmonary and mitral valves. INFLUENCE OF THE RESPIRATORY PRESSURE ON THE DILA- TATION AND CONTRACTION OF THE HEART. The variations in pressure to which all the parts within the thorax are subjected by its inspiratory expansion and expiratory contraction exert a visible influence on the diastole and systole of the heart. The conditions in various positions of the resting thorax with the glottis open will be considered first. The diastolic dilatation of the cavity of the heart is brought about by the elastic traction of the lungs, as well as by the inflow of venous blood and the elastic stretching of the relaxing muscular walls. This traction is greater in proportion as the INFLUENCE OF RESPIRATORY PRESSURE ON THE HEART. 123 lungs are more fully expanded (inspiration), and become less effective in proportion as the lungs have already been contracted (expiration). From this it follows : 1. That in the most extreme expiratory position of the thorax, with the greatest possible contraction of the pulmonary tissue, when, there- fore, what is left of the effective elastic traction of the lungs is exceedingly slight, but little blood enters the cavities of the heart; the heart during diastole is small and contains but little blood. Accordingly, the systolic contractions will be small, that is, a small pulse results. 2. In the most extreme inspiratory position, when the elastic lungs are distended to their utmost, the force of the elastic traction of the lungs is, naturally, greatest, being in fact equivalent to 30 millimeters of mercury. The effect of this traction may be great enough to counter- act the contractions of the thin-walled auricles and auricular appendages and prevent these structures from emptying their contents completely into the ventricles. In cases of cardiac weakness it would even appear as if the ventricular activity were impaired by the strong elastic pulmo- nary traction, as the diminution in the strength of the heart-sounds that is sometimes observed attests. The heart, therefore, is greatly distended in diastole and filled with blood ; nevertheless the resulting pulse-waves may be small in consequence of the limitation of auricular activity. Thus, Bonders often found the pulse smaller and slower. 3. When the thorax is in the position of moderate rest, a condition in which the elastic traction of the lungs is of moderate strength only, namely, 7.5 millimeters of mercury, the conditions for the action of the heart are most favorable. On the one hand, diastolic distention of the cavities of the heart is adequate, and, on the other hand, their complete evacuation during systole is not impeded. A much greater influence on the action of the heart is exerted by the increase or diminution in the intrathoracic pressure produced voluntarily by muscular action. 1. If the thorax is first brought into the position of deepest inspira- tion, then the glottis is closed, and now the space within the chest is greatly reduced with the aid of the expiratory muscles; the cavities of the heart may be so greatly compressed as to cause momentary sus- pension of the movement of the blood within them. In this position the elastic traction is greatly diminished, and in addition the pulmonary air, which is under high tension, exerts pressure on the heart and the intrathoracic vessels. As no venous blood can enter the thoracic cavity from without, the visible veins become enlarged, the blood is driven more rapidly into the left heart, and the latter empties itself into the circulation as quickly as possible. The lungs are, as a result, anemic and the cavities of the heart empty. Therefore, there is plethora in the greater circulation, associated with anemia in the lesser and in the heart. The heart-sounds cease, the pulse disappears. 2. If, conversely, the glottis is closed, while the thorax is in the position of most extreme expiration, and the thoracic cavity is now for- cibly dilated in inspiration, the heart is strongly dilated; for the cavities of the heart are distended not only by the elastic traction of the lungs, but also on account of the extreme rarefaction of the pulmonary air. The contents of the veins are poured copiously into the right heart, and in proportion as the right auricle and the ventricle are capable of 124 INFLUENCE OF RESPIRATORY PRESSURE ON THE HEART. overcoming the outward traction, the blood-vessels of the lungs will be distended with blood. Much less blood will be driven out of the left heart, so that the pulse may even be temporarily arrested. The result is an overdistended, enlarged heart and ' the presence of an increased amount of blood in the lesser circulation, as compared with the greater. As, when the breathing is normal, the tension of the pulmonary air is diminished during inspiration and increased during expiration, this normal alternation of pressure tends to assist the circulation: inspira- tion hastens the venous and lymphatic flow through the venae cavae (if the axillary or the jugular vein is opened during an operation, air may be sucked in and cause death) and thus favors complete diastole ; FIG. 36. Apparatus for the Demonstration of the Influence of Respiratory Expansion (II) and Contraction (I) of the Thorax on the Heart and the Circulation. expiration hastens the movement of blood into the arterial system and favors systolic emptying of the heart. At the same time the val- vular arrangement of the heart secures a constant direction to the accelerated blood-current. The elastic traction of the lungs also exerts a favorable influence on the lesser circulation, which is contained entirely within the thorax; for the blood within the pulmonary capillaries is under the same pres- sure as the pulmonary air, while that of the pulmonary veins is under lower pressure, as the elastic traction of the lungs by distending the left auricle necessarily hastens the flow of blood from the pulmonary veins into the left auricle. On the other hand, the elastic traction of MOVEMENT OF THE BLOOD IN THE CIRCULATION. 125 the lungs is prevented from interfering to any marked degree with the action of the right ventricle and, therefore, with the movement of blood through the pulmonary artery, because of the sufficient resistance of the blood, right ventricle and the pulmonary artery against the elastic pulmonary traction. The apparatus illustrated in Fig. 36 shows clearly the influence of inspiratory and expiratory movements on the expansion of the heart and on the current of blood in the large vascular channels leading to and from the heart. The large glass bottle represents the thorax, and its bottom has been replaced at D by an elastic rubber membrane, which represents the diaphragm. ' P P are the lungs; L the trachea, the entrance to which (glottis) may be closed by means of a stop- cock; H is the heart; E represents the course of the venae cavae; and A the aorta. When the tracheal stop-cock is closed and the expiratory position, as shown at I, is established by elevating the membrane D, with diminution in the size of the thoracic cavity, the air in P P is condensed, while at the same time the heart H is compressed; the venous valve closes, while the arterial valve is opened and the fluid is driven out through A. The manometer M, inserted into the flask, shows the increased intrathoracic pressure. Again, when the stop-cock 1 is closed (in II), and the membrane is strongly depressed, the lungs pp expand, and with them the heart h. The venous valve opens, while the arterial valve closes, and the venous blood enters the heart through e. Thus, inspiration always hastens the venous and inhibits the arterial flow, while expiration inhibits the venous and hastens the arterial flow. If the glottis (L and 1) remains open, the air in P P and p p naturally is changed as the thorax passes from the inspiratory to the expiratory position (D and d). Accordingly, the effect on the heart (H and h) and on the blood-vessels is smaller, but even under such conditions it must persist in small measure. THE MOVEMENT OF THE BLOOD IN THE CIRCULATION. TORICELLPS THEOREM ON THE VELOCITY OF ESCAPE OF FLUIDS. According to Toricelli's law, the velocity (v) with which a fluid escapes, for example, through an opening in the floor of a hollow cylindrical vessel, is equal to the velocity that a freely falling body would attain in falling from the level of the fluid to the level of the open- ing (the height of the propelling force h) . Hence v = 1/2 g h; in which g = 9.8 meters. The velocity of outflow increases, as has been shown experimentally, as the height of the propelling force (h) increases, and it preserves the ratio of i, 2, 3 as the propelling force increases in the ratio of i, 4, 9; that is, the velocity of outflow is proportionate to the square root of the height of the propelling force. It thus follow r s that the velocity of outflow depends solely on the distance between the level of the fluid and the opening, and not on the nature of the escaping fluid. Whenever a fluid is found escaping with a definite velocity, the force that causes the flow may be expressed by the height of a column of fluid (h) in a vessel the height of the pro- pelling force. Toricelli's law, however, is applicable only when all FIG. possible resistance that may be offered to the escape of the fluid is left out of account. As a matter of fact, certain resisting forces are present in any physical ex- periment of this kind. Hence, the force that is ex- pressed by the height of the propelling force (h) not only causes the escape of the fluid, but also overcomes the sum of all the resist- ances. These two forces may be expressed by the heights of two columns of water superposed the one upon the other ; namely, by the height of the velocity 37. Pressure- v e s s e 1 Filled with Water: h, height of the column of fluid; F, height of the velocity; D, height of the resistance. 126 PROPELLING FORCE, VELOCITY AND LATERAL PRESSURE. F (which effects the velocity of escape) and the height of the resistance D (which overcomes any resistance that may be present) : hence h = F -f- D. PROPELLING FORCE, VELOCITY AND LATERAL PRESSURE. If a fluid passes through a tube (which it completely fills) , the first thing to determine is the propelling force h with which the current flows at different points in the tube. The degree of the propelling force depends on two factors: 1. The velocity of the current, v; 2. The pressure (resistance-height) to which the fluid is subjected at different points in the tube, D. 1. The velocity of the current v is determined: (a) from the lumen of the tube 1, and (6) from the quantity of fluid q, that passes through the tube in a given unit of time. Then v = q : 1. Both values, q as well as 1, can be deter- mined directly by measurement. The circumference of a circular tube, the diameter of which is d, is 3.14 X d. The cross-section (the lumen of the tube) is 1 = - - X d 2 . After the value of v has been determined in this way, the so-called velocity- height F (of hydraulic engineers) can be estimated from v; that is, the height from which a body would have to fall in a vacuum in order to acquire the velocity of v. This is F = (in which g indicates the distance through which the body falls in one second, or 4.9 meters). 2. The pressure D (resistance-height) is measured directly at various points in the tube by inserting manometer- tubes (Fig. 38). The propelling force at any selected point in the tube will thus be: For experimental investigation the large cylindrical pressure- vessel (Fig. 38, A) may be used, within which by a suitable arrangement water can be maintained at a constant level h. The rigid tube a b, passing off from the bottom of the vessel, and of uniform size, is provided with a number of vertical tubes (i, 2, 3) consti- tuting a piezometer, for the measurement of the pressure; at the extremity b the tube is provided with an opening di- rected upward. From the lat- ter the water, providing the level at h remains the same, will be thrown to a constant height, and this distance is equivalent to F, the velocity- height. As the pressure D lt D 2< D 3 in the manometric tubes 1,2,3 can be read off directly, III * " ' ' FIG. 38. A Pressure-vessel, A, with Outflow Tube, a b, and Manom- eters, Di,D 2 D 3 , Inserted at Different Points. it follows that the propelling force of the water at the posi- tion of the tubes I, II, III is respectively h = F -f D t ; F + D 2 ; F + D 3 . At the extremity of the tube (at b) where D t =o,h = F + o, hence h = F. Within the pressure- vessel itself, it is the constant force h .that influences the movement of the fluid. It is, therefore, at once apparent that the propelling force of the water has become progressively smaller from the point where the fluid enters the tube from the pressure- vessel to the end of the tube b. The water in the pressure-vessel falling from h rises at b only to the height F. This diminution in the propelling force is due to the resistances encountered by the current in the tube, which neutralize a part of the kinetic energy (that is, convert it into heat). As, when the water has reached b, the motor power h in the vessel has been re- duced to F, the difference having been neutralized by the resistances, the sum of these resistances must be D = h - F, from which it follows that h = F -}- D, METHOD OF ESTIMATING THE RESISTANCES. 127 METHOD OF ESTIMATING THE RESISTANCES. When a fluid passes through a tiibe of uniform caliber throughout its entire length, the propelling force h diminishes progressively in consequence of the resistances that operate uniformly at every point. The sum of all the resistances in the tube is, therefore, directly proportional to its length. In a tube of uniform caliber the fluid passes through each transverse section at a constant velocity; hence v (and, therefore, F) is the same at any point in the tube. The diminution that takes place in the propelling force h can, therefore, be due only to a diminution of the pressure D, as F remains the same everywhere (and h "= F -f D). The experiment with the pressure- vessel shows, in fact, that the pressure progressively diminishes toward the discharging extremity of the tube. In a tube of uniform width the pressure-height found to prevail in the manometer-tube is the expression of the sum of the resistances that must be overcome by the current in its course from the point examined to the free discharge-opening of the tube. Forms of Resistance. The resistances encountered by a stream of fluid reside first of all in the cohesion of the fluid-particles. The outermost parietal layer of the fluid, which is in contact with the tube, remains absolutely quiescent during the passage of the current. All the other layers of the fluid, which may be concerned as a series of concentric cylinders one within the other, move with a progressively increasing velocity from the periphery to the axis of the tube, while the axial thread itself finally represents the most rapidly moving portion of the fluid. In the displacement of these cylindrical layers of fluid at their surfaces of contact, the particles of fluid in juxtaposition must naturally be pulled apart and a portion of the active propelling force will be lost. The degree of resistance depends essentially on the degree of cohesion between the particles of fluid; the more intimate the cohesion between the fluid-particles, the greater will be the resistance; and conversely. It is thus evident that the resistances encountered by the viscous blood in its passage must be greater than those that would be encountered, for example, by water or ether. Four and one-half times as much pressure would be required to drive the same quantity of blood as of water through a tube. Heat diminishes the cohesion of the particles and it is, therefore, a means for diminishing the resistance encountered by the current. It is also evident that the resistances are only the result of movement, as the forcible separation of the fluid-particles does not begin until the column is set in motion. It is, further, obvious that the greater the velocity of the current the greater the number of fluid-particles that are torn apart in a unit of time the greater will be the sum of the resistances. The parietal layer of fluid in contact with the surface of the tube remains, as has been said, in absolute quiescence; it follows, therefore, that the material composing the walls of the tube has no influence on the resistances. INFLUENCE OF INEQUALITIES IN THE SIZE OF THE TUBE. When the velocity of the current remains the same, the intensity of the resistances depends on the diameter of the tube; the smaller the diameter the greater the resistance, and the larger the diameter the less the resistance. The resistances, however, increase more rapidly in narrower tubes than the diameter of the tubes increases. This has been proved by experimental investigation. In tubes that exhibit inequality in size in their course, the velocity of the current varies, being naturally slower in the wide portions and more rapid in the narrower portions. In general the velocity of the current in tubes of unequal caliber is inversely proportional to the transverse section of the different portions of the tube, that is, if the tubes are cylindrical inversely proportional to the square of the diameter of the circular transverse section. While in tubes of uniform size the propelling force of the moving fluid dimin- ishes uniformly section by section, the diminution is not uniform in tubes of unequal width; for since, as has just been shown, the resistance is greater in a narrow than in a wide tube, the diminution in the propelling force must naturally be greater in the narrow places than in the wide places. At the same time, i't has been shown that the pressure in the wider places is greater than the sum of the resistances still to be overcome; while, on the other hand, at the narrower places it is smaller than the sum of these resistances. Curvature and tortuosity of the vessels give rise to new resistances. In con- sequence of centrifugal force the fluid-particles cling more closely to the convex 128 MOVEMENT THROUGH CAPILLARY TUBES. side of the arch and thus encounter a greater resistance to their progress than on the concave side. When the tube divides into two or more branches, the propelling force is also diminished on account of the creation of additional resisting forces. When a current is divided into two smaller currents, some fluid-particles will be retarded, while others will be accelerated on account of the unequal velocity of the various layers of the fluid. Many particles that in the main current, as a part of the axial stream, had the greatest velocity will in the secondary currents when situated in the parietal layers move more slowly; while, conversely, many parietal layers in the main current become more centrally situated in the secondary current with increased velocity. As a result of the resistance thus produced a part of the propelling force is naturally lost. The separation of the fluid-particles as the current divides has a similar effect. If, on the other hand, two tubes join to form a single tube, additional resistance acting in a manner opposite to that described must lessen the propelling force. The sum total of the mean velocity in both branches of the current is independent of the angle formed at the point of division. The opening of a lateral branch that forms part of a tube accelerates the main current to the same degree, irrespective of the size of the angle formed by the lateral branch with the main tube. MOVEMENT THROUGH CAPILLARY TUBES. The movement of fluids through capillary tubes is, in accordance with the capillary attraction prevailing in capillary vessels, and in contravention of the laws that have just been developed, governed by certain rules, for the formulation of which credit is due Poiseuille. These rules are as follows: 1. The quantity of fluid that escapes from a capillary tube is proportional to the pressure. 2. The time necessary for the escape of a like quantity of fluid (the pressure, the diameter of the tube, and the temperature remaining the same) is propor- tional to the length of the tube. 3 . The products of the outflow (all other conditions remaining the same) vary with the fourth power of the transverse diameter. 4. The velocity of the current is proportional to the pressure-height and to the square of the diameter, and inversely proportional to the length of the tube. 5. The resistances in the capillary tubes are proportional to the velocities of the current. CONTINUOUS AND UNDULATORY MOVEMENT IN ELASTIC TUBES. If an uninterrupted, uniform stream of fluid is permitted to flow through an elastic tube, the movement of this current is subject to the same laws that govern its passage through rigid tubes. If the propelling force increases or diminishes, the elastic tubes are either dilated or constricted, and their relation to the column of fluid is, therefore, simply like that of wider or narrower rigid tubes. If, however, successive amounts of fluid are introduced at intervals into an elastic tube entirely filled with fluid, the initial portion of the tube will be suddenly distended in accordance with the amount of fluid introduced. The impact imparts to the fluid-particles an oscillatory movement, which rapidly communicates itself to all the fluid-particles from the beginning to the end of the tube ; there results a positive wave, which rapidly propagates itself through the entire tube. If the elastic tube be closed at its peripheral extremity, the positive wave will rebound at the point of closure; it becomes a positive recurrent wave and it may even pass backward and forward repeatedly, becoming gradually smaller and smaller, until it finally subsides. Hence, in a closed tube of such character, the sudden periodic impulsion of a mass of fluid produces only a wave-like movement, that is, merely an oscillatory movement or the movement of a form. 3. If, however, additional amounts of fluid are at intervals pumped into the initial portion of an elastic tube entirely filled with fluid already in continu- ous movement, the continuous movement is combined with the undulatory movement. In such a case the continuous movement of the fluid, that is, the displacement or movement of the fluid in mass through the tube, must be rigidly distinguished from the undulatory or oscillating movement, the movement of the change in form of the column of fluid. The former is a translatory, the latter an oscillatory movement. The continuous movement is slower in elastic tubes v while the undulatory movement is more rapid. STRUCTURE AND PROPERTIES OF THE BLOOD-VESSELS. I2Q The conditions in the arterial system are the same as those just described. The blood in the arteries is already engaged in continuous motion from the root of the aorta to the capillaries (continuous movement) ; and the injection at inter- vals of a mass of blood into the root of the aorta with each systole of the left ventricle produces a positive wave (pulse) , which propagates itself with great rapidity to the end of the arterial system, while the constant movement progresses much more slowly. It is of great importance to compare the movements of fluids in rigid tubes with the movements of fluids in elastic tubes. When a certain quantity of fluid is forced into a rigid tube under a certain pressure, an equal quantity of fluid will at once escape from the end of the tube, unless such a result is prevented by the development of special resistances. The conditions are, however, different in the case of an elastic tube. Immediately after the injection of a definite quantity only a relatively small quantity of fluid escapes at first, the escape of the re- mainder taking place only after the injecting force has subsided. If equal quantities of fluid are injected at intervals into a rigid tube, a corre- sponding amount escapes with each impulse and the discharge continues as long as the impulse, and the pause between each two periods of escape is always equal to the period between two impulses. In the case of elastic tubes the conditions are different. As the escape of the fluid continues for some time after the cessation of the impulse, it will always be possible to establish a continuous outflow through elastic tubes by making the interval between two injections shorter than the duration of the outflow that takes place after the impulse has been completed. Thus, the periodic injection of fluid into a rigid tube produces an isochronous, sharply limited outflow of fluid, which can become permanent only when fluid enters the tube in a continuous stream. In the case of elastic tubes, on the other hand, intermittent introduction of fluid produces under the same conditions a continuous outflow with systolic reinforcement. Hamel's investigations have shown that elastic tubes permit the passage of more fluid when they are supplied in a rhythmical pulsatory manner than when the fluid enters in an uninterrupted stream under constant pressure. The advan- tage of the rhythmical impulse for the propulsion of the circulating fluid, as com- pared with a uniform pressure, appears to reside in the fact that the alternating movement preserves the elasticity of the arterial walls. STRUCTURE AND PROPERTIES OF THE BLOOD-VESSELS. The large blood-vessels in the body are designed solely for the purpose of acting as conducting canals for the mass of blood, while the thin-walled capillary vessels effect the interchange of substances between the blood and the tissues and in the opposite direction. The Arteries differ from the veins in the possession of thicker walls in con- sequence of the considerable development of muscular and elastic elements, as well of a greatly developed middle tunic, with a relatively thin adventitial coat. The walls of the arteries consist of three coats (Fig. 39) : The intima is lined on its inner surface by a nucleated endothelium (a) consisting of flat, irregular, oblong cells. External to the endothelium is a thin, finely granular layer containing more or less distinct fibers and numerous spindle-shaped or stellate protoplasmic cells embedded in a corresponding system of plasma-canals. To the outer side of this is the inner elastic layer (b), which in the smallest arteries is represented by a structureless or fibrous, elastic mem- brane and in the medium-sized arteries by a fenestrated membrane; while in the largest it assumes the appearance of a stratified, fibrous or fenestrated, elastic membrane consisting of two or three layers and united by connective tissue. All of the larger and medium-sized arteries contain longitudinal fibers situated between two elastic plates. Acting together with the circular fibers they are capable of narrowing the caliber of the vessel ; but they possess also the faculty of widening the lumen and maintaining it at a uniform width. On the other hand, it is im- probable that they are capable of independent action or that such independent action is capable of dilating the vessel. The middle coat has for its most characteristic constituent unstriated muscle- fibers (c). In the smallest arteries this appears to be composed of scattered, transverse, smooth muscle-fibers occupying an intermediate position between the intima and the adventitia. The connecting material consists of a finely granular tissue traversed by a few delicate elastic fibers. Passing from the smallest to the 9 130 STRUCTURE AND PROPERTIES OF THE BLOOD-VESSELS. smaller arteries, the number of unstriated muscle-fibers increases progressively until they form a strong layer of circular muscle-fibers with almost complete dis- appearance of the connecting substance. The outer elastic layer forms the bound- ary between the media and the adventitia. In the large arteries the connecting substance greatly predominates over all other tissues: Separated by layers of delicate fibrous tissue there are numerous (as many as 50) thick, elastic, fibrillated or fenestrated membranes arranged in concentric layers and chiefly in the trans- verse direction. Scattered here and there between these membranes are occa- sional smooth muscle-cells arranged transversely, less commonly obliquely, or longitudinally. The initial portions of the aorta and pulmonary artery, the arteries in bones and the retinal arteries are devoid of muscle-tissue. The descending aorta and the common iliac and popliteal arteries possess oblique and longitudinal muscle- fibers lying among the transverse fibers. The renal, splenic and internal sper- matic arteries contain longitudinal bundles at the inner surface of the media; the umbilical arteries, which are exceedingly rich in muscle- tissue, contain longitudinal bundles both on the inner and on the outer surface. The external or adventitious coat in the smaller arteries is a delicate, structureless membrane containing a few protoplasmic cells. In somewhat larger vessels there is an additional layer of elastic tissue of delicate fibers containing strands of fibrillated con- nective tissue (d) . In the medium-sized and largest arteries the greater part of the ad- ventitia consists of bundles of fibrillated connective tissue containing connective-tissue cells, and not infrequently an admixture of fat-cells, running obliquely and crossing each other at numerous points. Among them and chiefly toward the media are found fibrous or fenestrated elastic layers. At the boundary between the adventitia and the media the elastic elements in the smaller and medium- sized arteries fuse to form a more indepen- dent elastic membrane (Henle's outer elastic membrane). Longitudinal unstriated mus- cle-fibers in scattered bundles are found in the adventitia of the arteries of the penis, of the descending aorta, the renal, splenic, in- ternal spermatic, iliac, hypogastric, and superior mesenteric arteries. Bonnett suggests the following natural division of the layers of the arterial wall: i . The intima embraces the endothelial tube and the tissues as far as the inner elastic layer. 2 . The media contains all those parts that are situated between the inner and the outer elastic layer. 3. The adventitia includes the layers found to the outer side of the elastic membrane. The Capillaries, which undergo frequent division without suffering diminu- tion in caliber, and in their subsequent course unite again, have diameters varying from 5 to 6 fj, (retina, muscles) to from 10 to 20 // (bone-marrow, liver, choroid) The tubes are formed of a single layer of nucleated endothelial cells, with protoplasmic cell-bodies, which in the smaller tubes are spindle-shaped and in the larger vessels are more polygonal (as is the case with the cells ot serous cavities); they are connected by numerous intercellular bridges in the depths of the cell-substance (like epithelial cells). The boundaries of the cells are demonstrable as black lines by injection of a solution of silver nitrate stained cement-substance exhibits in some places intercalated areas of larger size. Whether these are to be regarded as true openings or stomata, through which it is possible for red and white cells to escape, or merely as denser aggre- gations of the stained cement-substance is still an undecided question. Delicate FIG. 39. Small Arterial Twig Showing the In- dividual Layers of the Arterial Wall: a, endothelium; b, elastic inner coat; c, layer of circular muscle-fibers; d, con- nective-tissue adventitia. STRUCTURE AND PROPERTIES OF THE BLOOD-VESSELS. anastomosing fibrils derived from non-medullated nerves terminate by small end-plates in the capillary walls. Ganglia in communication with the nerves of capillary vessels are found only in the distribution of the sympathetic nerves. The minute blood-vessels that communicate directly with the capillaries possess, in addition to endothelium, an entirely structureless investing membrane. The Veins differ from the arteries in the main in the fact that they have a larger caliber than the corresponding arteries and thinner walls on account of the much feebler development of the elastic and muscular elements. Among the latter longitudinal fibers are much more commonly found than transverse. Veins are also distinctly more distensible with the same degree of traction. The adven- titia is as a rule relatively the thickest coat. The presence of valves is limited to certain areas of the body. The intinia or internal coat is provided with short endothelial cells, beneath which, in the smallest veins, is a structureless layer, which in the somewhat larger vessels is composed principally of longitudinal elastic fibers (always thinner than in the arteries). In the large veins this layer may assume the character of a fenestrated membrane, which here and there in the femoral and iliac veins is even duplicated. It is held together by a delicate connective tissue containing spindle-cells. The intima in the femoral and popliteal veins contains a few scattered muscle- fibers. The media or middle coat in the larger veins is constituted of alternate layers of elastic and muscular elements, with a fairly abundant fibrillar connective tissue. The media is always thinner, however, than in the corresponding arteries. The number of these alternating layers becomes progressively smaller in the following veins, in the order of their enumera- tion: popliteal vein, veins of the lower extremity, veins of the upper extremity, superior mesenteric, the remaining veins of the abdominal cavity, the hepatic, pulmonary, and coro- nary veins. The following veins are altogether devoid of mus- cle-tissue: the veins of bones, muscles, the central nervous system and its membranes, the retinal veins, the superior cava with the large trunks that empty into it, and the upper portion of the inferior cava. In these vessels the media is much more feebly developed. In the smallest veins the media consists merely of a delicate fibrillar connective tissue in which a few scattered longitudinal and transverse unstriated muscle-cells make their ap- pearance as the center of the circulation is approached. The adventitia or external coat of the veins is, generally speaking, thicker than that of the corresponding arteries. It always contains more abundant connective tissue, usually consisting of longitudinal fibers, and on the other hand fewer large- meshed networks of elastic elements. Some veins, however, contain also longi- tudinal muscle fibers: the renal vein, the portal vein, the inferior cava in the hepatic region, the veins of the lower extremity. The valves consist of finely fibrillated connective tissue in which stellate cells are embedded; the convex surface of the valves is covered with a network of elastic fibers, and both surfaces are invested with endothelium. The valves contain many muscle-fibers. The sinuses of the dura mater are spaces lined with endothelium between duplicatures, or cleft-like invaginations of this membrane. Cavernous spaces may be regarded as having been produced by numerous divisions and anastomose's of fairly large veins of unequal size, closely following one another. The vessel-wall frequently appears cribriform or like a sponge the FIG. 40. Capillary Vessels, the Boundaries of the Cells (Cement- substance between the Endothelial Cells) have been Stained Black with Silver Nitrate and the Nuclei of the Endothelial Cells Made Prominent by Staining. 132 STRUCTURE AND PROPERTIES OF THE BLOOD-VESSELS. interior traversed by trabeculae or threads. The surface directed toward the blood is covered with endothelium. The investing wall consists of connective tissue, which is often quite firm and tendinous, as in erectile tissue. It not infre- quently contains unstriated muscle-fibers. An example of an analogous cavernous formation in arteries is found in the coccygeal gland of man. This mysterious structure, which is richly supplied with sympathetic nerve-fibers, consists of nucleated connective tissue and represents a convolution of ampulliform or spindle-shaped dilatations of the median sacral artery, traversed and surrounded by unstriated muscle-fibers. The vasa vasorum do not differ in structure from other vessels of similar caliber. Intercellular blood-channels devoid of walls are present in the granulation-tissue of wounds. At first nothing but blood-plasma is found between the constituent cells, and it is not until later that blood-cells are driven through the channels by the blood-current. In the incubated egg the primary basis of the blood-vessels is formed in a manner similar to that of the formative cells of the germinal layer. The blood-vessels without walls in the bone-marrow and in the spleen are con- sidered on p. 43. Among the properties of blood-vessels their contractility should be mentioned first, that is, the ability to contract by virtue of the unstriated muscle-fibers contained in their walls. The intensity ' and force with which this contraction takes place are proportional to the degree p of development of the muscle-tissue. Heat causes contraction of the blood-vessels (in the mesentery of the frog) . Excised arteries contract when filled with dilute alkaline solutions, digitalin, atropin, and antiarin. The isolated apex of the heart also beats more freely in alkaline solutions. When the vessels are filled with a dilute solution of lactic acid they dilate, and the apex of the heart when immersed in such a solution also beats more rapidly. According to Roy, blood-vessels undergo shortening under the influence of heat, if precautions are taken to prevent evaporation and the load remains the same. If blood containing an admixture of certain substances such as amyl nitrite, chloral hydrate, morphin, quinin, and atropin is allowed to flow through the vessels of a recently excised, living organ, dilatation takes place; urea and sodium chlorid have the same effect on the renal vessels; while digitalin and veratrin cause contraction. The capillaries also possess the power of dilating and contracting, derived from the protoplasmic granules of the cells of which they are composed. The capillaries have been designated "protoplasm in tubular form," and motor phenomena have been observed in them, especially after irritation in the living animal. Strieker observed this chiefly in the capillaries of young frog- spawn. At a later period of the animal's life the reaction of the capillaries to stimuli is much less distinct. Rouget observed the same phenomena also in new- born mammals. Similar observations have been made by Golubew and Tarchanoff. Accordingly, the shape of individual cells varies with the quantity of blood con- tained in the vessels. In greatly distended vessels the cells are flat; but when the vessel is collapsed, the cells are more cylindrical and project into the lumen. Among the physical properties of blood-vessels their elasticity should next be mentioned. The elasticity is slight, that is, the vessels offer little resistance to the distending forces, such as pressure or trac- tion; but it is, at the same time, complete, that is, after the distending force has ceased to act, the vessels regain their previous form. According to Ed. Weber, Wertheim and A. W. Volkmann, the length of blood- vessels (like that of moist portions of the animal body generally) does not increase in proportion to the weight employed to extend it, but the elongation is considera- bly less with progressive increase in the weight. Hence the extensibility of the dead artery is greatest when it has been slightly distended by intravascular pres- PULSE-MOVEMENT. sure. After repeated experiments, however, Wundt was led, as a result of ex- perimental observations, to the conclusion that blood-vessels also are subject to the general law of elasticity mentioned. He maintains that it is necessary to take into consideration not only the first distention that occurs after the application of the load, but also the "elastic after-effect" that follows gradually. This terminal distention, which often proceeds slowly, is so gradual during the last moments that observation with a magnifying lens is necessary to determine when the condition of definitive distention is completed. Deviations from the general law occur; for when a certain load is exceeded, lesser degrees of distention and at the same time permanent changes not infrequently result. A normal vein may be stretched at least 50 per cent, without exceeding the limit of elasticity. Pathological. Nutritive disturbances modify the elasticity of the arteries. When death has been preceded by marasmus, the arteries are found relatively more dilated than under normal conditions. Beginning connective-tissue forma- tion in the intima, combined with fatty degeneration, at first increases the dis- tensibility and diminishes the strength of the wall. As the development of the connective tissue progresses in cases of arteriosclerosis, the elasticity and firmness of the arteries are again augmented. Diminished distensibility is found also in connection with atheroma, in cases of nephritis and in the arteries of drunkards. A property peculiar to the walls of the blood-vessels is their power of cohesion, which enables them to resist rupture, even when the in- ternal tension is considerable. It has been found that the carotid artery does not rupture until the internal pressure has been raised artificially to fourteen times the normal. The resistance of veins to rupture is relatively greater than that of arteries with the same thick- ness of wall. According to Grehant and Quinquaud the carotid and iliac arteries in man resist a pressure up to eight atmospheres and the veins more than half of this amount. Pathological. Diminished power of cohesion of the blood-vessels, especially the arteries, is not uncommon in old age. PULSE-MOVEMENT. TECHNIC OF PULSE-EXAMINATION. The physicians of antiquity devoted more attention to abnormal excitation of the pulse than to the normal pulse. Thus, Hippocrates (460-377 B. C.) speaks only of the former condition and applies to it the term ojvyptf. Later, Herophilus (300 B. C.) in particular compared the normal pulse (Trafy6fi with the abnormally excited pulse. He laid especial stress on the time-relations existing between dilatation and contraction of the arterial tube and defined more accurately the properties, volume, fulness (a^vy^ raxvg) and frequency (a 46. Dudgeon's Sphygmograph. twice in the descending limb, the sphygmo- graphic curve is called dicrotic or tricrotic. When, as happens if the pulse- beats follow one another in rapid succession, the succeeding beat cuts off the recoil-elevation of the preceding curve, the curve is called monocrotic. Method of Making Sphygmographic Tracings. The tracings are recorded on smooth glazed paper like that used for visiting cards, which has been covered with a delicate translucent layer of soot by exposure over burning camphor or a smoking lamp. The tracing is fixed by immersing the paper in a solution of shellac and alcohol, after which it is allowed to dry. Mensuration of Sphygmographic Tracings. When a tablet is made to move at a uniform rate by means of clockwork, the vertical height and horizontal length of individual portions of the tracing can be measured with a fine rule. The distance traversed by the tablet in a second being known, it is possible by actual measurement to compute the duration of the individual portions of the pulse-movement. Accurate measurements of this kind must be made under the microscope with the aid of an ocular micrometer, a low magnification and direct illumination being employed. The sections to be measured are placed be- tween two lines that, in the case of sphygmographs like Marey's, which make a curved tracing, must be arcs of a circle (of which the writing lever is the radius) , and in the case of the angiograph must be vertical. An especially convenient method consists in recording the curve on a tablet attached to one end of a vibrating tuning-fork (Fig. 60). Another less accurate method consists in recording the vibrations of a tuning-fork on the tablet of the sphygmograph at the same time that a Sphygmographic tracing is being recorded, the latter being above the tuning-fork record. The Gas-sphygmoscope. To meet the objection that has frequently been urged against instruments for registering the pulse, namely that the secondary elevations observed in the sphygmogram are due to the after- vibrations of the apparatus from inertia, Landois constructed a gas-sphygmoscope, in which the movement of solid bodies is excluded and any after-vibration of inert masses that have been set in motion is, therefore, impossible. The superficial arteries, whose movement is communicated to the overlying skin, will, naturally, through the movement imparted to this layer of the skin, cause also a movement in the contiguous layers of air. The thin layer of air above the pulsating cutaneous area (Fig. 48) a is excluded by means of a shallow 138 INSTRUMENTS FOR INVESTIGATING THE PULSE. metallic gutter b, which is placed on the skin so that its concavity covers the artery like a small tunnel. The narrow space between the wall of the tunnel and the skin is filled with illuminating gas. To this end one extremity of the metallic tunnel is connected with the gas-tube g, while the other extremity com- municates by means of a short rubber connecting piece x q with a small tube t, bent upward at an angle and the point of which is drawn out to a minute opening for the escape of the gas. The gas is allowed to pass through the metallic tunnel, under low pressure, the inflow being regulated so that the flame v is not more than a few millimeters long. It is readily seen that the flame increases in height synchronously with each pulse-beat and that the descent is interrupted by a distinct after-beat, von Kries photographed the image of the flame. The measurements of the accompany- ing curve are as follows : 1-2 = 7.5 = 0.121 sec. 13 = 16 = 0.258 1-4 = 22.5 = 0.363 i-5 = 39-5 = - 6 3 8 FIG. 47. Sphygmographic Tracing from Radial Artery Made with Landois' Angiograph the Attached 5 to a Vibrating Tuning-fork, indentation corresponds to 0.01613 sec. Each Hem-autography. If a freely exposed artery be divided in an animal so that the blood-stream spurts forth and is allowed to impinge on a glass plate or a sheet of paper moved vertically at some distance, the resulting tracing will coincide almost perfectly with the normal curve of the artery as recorded by the sphygmo- graph. In addition to the primary elevation (Fig. 49, P), the recoil-elevation (R) and the elasticity-elevations (e e) are appreciable. This self-registration of the FIG. 48. Landois' Gas-sphygmoscope. blood-wave furnishes a convincing proof that the movement is produced in the blood itself and is communicated as an undulatory movement to the arterial wall. By determining the quantity of blood contained in the several portions of the hemautographic tracing it is found that the quantity of blood that escapes from the divided artery during systole is to the quantity that escapes during diastole (that is during contraction and dilatation of the vessel) approximately as 7 : 10. The quantity of blood that escapes during a unit of time while the artery is di- lating is equal to a little more than twice the quantity that escapes during a unit of time while the vessel is contracting. THE PULSE-TRACING, THE RECOIL-ELEVATION AND THE ELASTICITY-ELEVATIONS. The sphygmogram presents an ascending limb, recorded during the distention (diastole) of the artery; the apex (Fig. 50, P); and the de- scending limb, which corresponds to the contraction (systole) of the ORIGIN AND PROPERTIES OF THE DICROTIC ELEVATION. artery. The most conspicuous features of the sphygmographic tracing are the two entirely distinct elevations in the descending limb of the curve. The more prominent of the two occupies approximately the center of the descending limb, where it appears as a distinct elevation (R); it is known as the dicrotic after-beat or, with reference to its origin, as the recoil-elevation. The sphygmographic tracing reproduces the chronological course of the pressure exerted by the undulatory movement of the blood on the arterial wall, the pad of the sphy gmograph , which is supported on a spring, rising and falling with the variations in pressure; the instrument therefore records "pressure- pulse." ORIGIN AND PROPERTIES OF THE DICROTIC ELEVATION. The recoil-elevation (also designated secondary or dicrotic) is pro- duced in the following manner: After the column of blood propelled into the arterial system by the ventricular systole has generated a positive wave, which, beginning at the aorta, extends rapidly to all of the arteries, even to the minutest arterial branches, in which it disappears, the arteries contract as soon as closure of the semilunar valves prevents the further entrance of blood. The elasti- city and the active contraction of the blood-vessels thus exerts a counter pressure on the blood-column. The blood is forced to seek an outlet. In its progress toward the periphery it finds no obstacle in its path, but the portion that escapes toward the center of the circulation recoils from the already closed semilunar valves. The impact of the blood sets up another posi- tive wave, which is again propagated into the arteries and disappears as before in the remotest minute branches. If, how- ever, there is sufficient time for the com- plete development of the sphygmographic tracing, a second reflected wave is pro- duced in the proximal arteries (especially in the short course of the carotids, but also in the arteries of the upper ex- tremities, but not in those of the lower extremities because of their great length) in the same way as the first. Just as the pulse appears somewhat later in the more peripheral arteries than in those nearer the heart, so the secondary wave, produced by the recoil of the blood from the aortic valves, also appears later in the more distant arteries. Both kinds of waves, the primary and the secondary pulse-wave, and possibly also the tertiary recoil -wave, originate at the same point and are propa- gated in the same way. The longer the distance to be traveled before they reach a given point in the artery, the later will be their arrival at that point. The following laws with regard to the recoil-elevation have been determined experimentally : FIG. 49. Hemautographic Tracing from the Posterior Tibial Artery of a Large Dog: P, primary pulse-wave; R, re- coil-elevation; e e, elasticity-eleva- tions. 140 ORIGIN AND PROPERTIES OF THE DICROTIC ELEVATION. i. The dicrotic elevation appears later in the descending limb of the curve the longer the artery, measured from the heart to the peripheral termination of the artery. (The curves in Figs. 47, 53 and 57 may be measured to confirm this point.) XIV xv FIG. 50. I, II, III, Sphygmographic tracings from the carotid artery; IV, from the axillary; V . IX, from the radial; X, bigeminate pulse from the radial; XI, XII, sphygmographic tracings from the femoral; XIII, from the posterior tibial; XIV, XV, from the dorsalis pedis. In all of the tracings P indicates the apex of the curve; R, the dicrotic elevation; e e, the elasticity-elevations; k, the elevation caused by the closure of the aortic semilunar valves. The shortest accessible arterial course is that of the carotids, where the dicrotic elevation attains its greatest height about 0.35 or 0.37 second after the beginning of the pulse. The next shortest accessible arterial course is that of the upper extremity, where the apex of the dicrotic elevation is traced about 0.36 or [0.38 or 0.40 second after the beginning of the pulse. The longest ORIGIN AND PROPERTIES OF THE ELASTICITY-ELEVATION. 141 course is that of the arteries of the lower extremity, in which the apex of the recoil-elevation is formed about 0.45 or 0.52 or 0.59 second after the beginning of the curve, in accordance with the size of the individual. In children and in small individuals the recoil-elevation occurs accordingly earlier in all of the arteries. If a rubber tube be connected with the carotid or the femoral artery of a dog, the sphygmographic tracing may be recorded also from this tube. Under such circumstances the interval between the beginning of the curve and the dicrotic elevation will naturally be directly proportional to the length of the tube. 2. The dicrotic elevation in the descending limb of the curve will be the lower and the more indistinct the greater the distance of the artery from the heart. It is not surprising that the secondary wave becomes smaller and more indistinct the further it must travel in the arterial tube. 3. The dicrotic elevation in the pulse will be more distinct the shorter and the more vigorous the primary pulse- wave. It is, there- fore, relatively largest with a short, powerful systole of the heart. 4. The dicrotic elevation is greater the greater the tension in the arterial tube. In Fig. 50 IX and X are recorded with low, V and VI with moderate, and VII with high tension of the arterial wall. Influences Affecting Vascular Tens-ion. A number of influences are known that affect the tension in the arterial tube. The tension is diminished by beginning inspiration, vasomotor paralysis, venesection, intermission of the heart's action, heat, and elevation of a part of the body. The tension is increased by beginning expiration, accelerated heart-action, stimulation of the vasomotor nerves, inter- ference with the flow of blood to the periphery (as by conditions of inflammatory stasis), certain poisons (such as lead), compression of other large arterial trunks, the effect of cold and of electricity on the small vessels of the skin, and inter- ference with the venous flow. Likewise, exposure of the arterial trunks is followed by increased vascular tension on account of the stimulation caused by the atmos- pheric air coming in contact with the arterial wall. Increased arterial tension is observed also in association with a variety of morbid conditions. When the ten- sion is high, the entire sphygmographic tracing is, as a rule, lower. In conformity with the conditions named, increased tension will be indicated by a lower, more indistinct dicrotic elevation; and diminished tension in the arterial tube, on the other hand, by an enlarged and more distinct dicrotic eleva- tion. A consideration of the laws governing the dicrotic elevation is of great practical significance in the study of the pulse. Moens asserts that the interval elapsing between the primary elevation and the dicrotic wave increases directly as the diameter of the vessel, and that the thickness of the wall diminishes as the coefficient of elasticity becomes smaller. ORIGIN AND PROPERTIES OF THE ELASTICITY-ELEVATION. In addition to the dicrotic elevation a series of more numerous, though much less distinct, often almost imperceptible, movements are appreciable in the sphygmographic tracing. These (marked e e in Fig. 50) are produced by the vibrations of the elastic vessel, which behaves like a tense elastic membrane when it is rapidly and vigorously stretched by the pulse-wave, just as a relaxed elastic sheet of rubber undergoes a series of oscillations when it is suddenly and vigorously stretched and made tense. Similarly, the elastic tube will exhibit oscillatory movements when it passes suddenly from a condition of tension to one of relaxation. These minor elevations produced in the sphygmographic tracing by the elastic vibrations of the arterial wall are known as elas- ticity-elevations. As the elasticity-elevations are due to the vibrations of the stretched coat of the blood-vessel, the following facts will be readily understood: 142 THE DICROTIC PULSE. 1. In the same artery the variations in elasticity increase in num- ber as the tension of the arterial wall increases. Especially high tension has been encountered chiefly during the cold stage of malarial fever (intermittent fever), and precisely in this connection has the most obvious increase in the elevations also been observed. 2. If the tension of the arterial wall is greatly diminished, the elas- ticity-elevations may disappear. As diminution in the tension favors the development of a dicrotic elevation, the two kinds of elevations have, with respect to their magnitude, an inverse relation to each other. 3. In the presence of diseases of the vessel-wall that diminish or even destroy its elasticity, the elasticity-elevations are either greatly diminished 'in size or altogether abolished. 4. The greater the distance of the artery from the heart, the greater will be the elasticity-elevations in the descending limb of the curve. 5. When the mean pressure in an artery is heightened on account of interference with the flow of blood in the arteries, the elasticity-eleva- tions are nearer the apex of the curve. 6. The elasticity-elevations vary in number and position in the sphygmographic tracings from the different arteries in the human body. When the arm is held in the vertical position, relaxation and diminution in the elastic tension appear in the course of five minutes in the arteries of the upper extremity, which at the same time contain less blood. The elevations that are designated elasticity-elevations are believed by Moens to owe their origin to numerous small waves that appear to be superadded to the dicrotic elevation. Grashey thinks them only in part due to elastic vibrations. The laws governing the movement of the pulse may be most readily demon- strated by means of investigations in regard to the undulatory movements in elastic rubber tubes, as has been done by Marey, Landois, Moens, Grashey, G. v. Liebig, and others, THE DICROTIC PULSE. Under the influence of excessive elevation of temperature the pulse in man is sometimes observed to be composed of two beats (Fig. 50), the first being large and the second small and apparently secondary to the first. A couple of these beats always correspond to a single systole of the heart. By the sense of touch it is quite possible to feel the two unequal beats separately. The study of the pulse with the sphygmograph has taught that the dicrotic pulse is only an exaggeration of the normal pulse. The palpable secondary beat is only a greatly magnified dicrotic elevation, which under normal conditions cannot be recognized by the palpating finger, but which, when increased by some morbid condition, becomes recognizable by the sense of touch. As regards the causes that are responsible for this increase in the size of the dicrotic elevation, Landois' investiga- tions have yielded the following results : 1. The production of a dicrotic pulse is favored by a short primary pulse- wave, such as occurs usually in the presence of fever, a condition in which the contractions of the heart are comparatively rapid and unproductive. 2. The dicrotic pulse is favored by reduction of the tension in the arterial system. A short systole combined with diminished arterial tension offers the most favorable condition for the production of the dicrotic pulse. Sometimes the dicrotic pulse is felt only in a certain arterial distribution, while in all the others the pulse-beat is single. This happens especially in the brachial artery on one or other side of the body. Under such circumstances the conditions for the production of dicrotism in the corresponding arterial area must be especially favorable. These conditions will be found in the local diminution of vascular tension in this area in consequence of paralysis of the vasomotor nerves con- trolling it. If the tension be increased, as can readily be done by compressing adjacent or other arterial trunks of considerable size or the corresponding veins, the dicrotic pulse is converted into a single pulse. In the presence of fever, dicro- tism appears to be due to the elevation of temperature (from 39 to 40 C.), which causes greater distention of the artery and shorter and quicker heart-beats. DIFFEREXCES IN THE TIME-RELATIONS OF THE PULSE. 143 3. It is absolutely indispensable for the production of the dicrotic pulse that the arterial wall possess its normal elasticity. In old persons with calcined arterial walls dicrotism does not appear. In Fig. 51, A, B, C illustrate the gradual transition from the normal radial curve (A) to the dicrotic pulse (B, C), in which the recoil-elevation (r) appears as an independent elevation. FIG. 51. Normal Pulse-production of the Dicrotic Pulse. P. caprizans P. monocrotus. If in the presence of dicrotism of febrile origin the pulse becomes more and more frequent, the next succeeding pulse-beat may begin before the descending portion of the recoil-elevation is completed (Fig. 51, D, E, F), or it may even begin at the apex (G) P. caprizans. Finally, if the next succeeding beat begins in the depression (z) between the primary elevation (p) and the recoil-elevation (r) , the latter disappears altogether, and the curve (H) assumes the monocrotic form. DIFFERENCES IN THE TIME-RELATIONS OF THE PULSE. FREQUENT AND INFREQUENT PULSE. In accordance with the number of pulse-beats in one minute, the pulse is designated either frequent or infrequent. Under the influence of fever or other agencies the number of pulse-beats may be considerably increased until they reach 120 or more. Reduction of the pulse-beats to about 40 is observed under certain normal conditions (during the puerperium, in states of hunger, and as an idiosyncrasy in some individuals) . In rare cases these limits may be exceeded in either direction. In periodic attacks as many as 250 pulse-beats have been counted. Such attacks must be designated pyknocardia (the term tachycardia is incorrect because rn^i^ is equivalent to quick). Abnormal infrequency or spanicardia (the term bradycardia is incorrect because fipafivf is equivalent to slow) also occurs; 15, 10, and even 8 beats in the minute have been counted. Under such conditions, disease of the cardiac nerves or of the muscle from over- exertion or disorders in the coronary circulation should be thought of. Deepening of the respiration without acceleration usually causes some increase in the frequency of the pulse. Accelerated but superficial' breathing is without effect, while deep, rapid respirations increase the number of pulse-beats. QUICK AND SLOW PULSE. When the development of the pulse-wave is such that the distention of the arterial tube goes on slowly to its maximum and collapse of the distended artery likewise occurs gradually, the slow pulse is produced; while under opposite conditions the quick pulse results. Among the factors that increase the quickness of the pulse are: slowness of cardiac action; greatly diminished resistance of the arterial coats; dilatation of the smallest arteries, diminishing the resistance to the flow of blood; greater proximity to the heart. The curve in a sphygmo- graphic tracing from a quick pulse is high and the apex pointed; a slow pulse yields a low sphygmographic curve, the ascending portion being particularly short, while the apex is broad. 144 CONDITIONS INFLUENCING THE FREQUENCY OF THE PULSE. CONDITIONS ^INFLUENCING THE FREQUENCY OF THE PULSE. In the normal adult male the number of pulse-beats is 71 or 72 in the minute, in the female about 80. Other factors that influence the frequency are : (a) Age: Beats in the Beats in the Minute. Minute. New-born 130140 ioth-1 5th year 78 1 year 120130 i5th-2oth . 70 2 years 105 2oth-25th 70 3 100 25th~5oth 70 4 97 6oth year 74 5 94 90 8oth year 70 10 years about 90 8oth~9oth year over 80 (b) The length of the body stands in a definite relation to the frequency of the pulse. Volkmann gives the formula p l == j^~ 1 in which P and P! represent the pulse-frequency and L and L 1 the body-length. Rameaux suggests the following formula: N x = Nj/j^' f in which N and N\ represent the ptilse-fre- quency and D and D x the body-length. By means of this formula the pulse- frequency has been calculated from the body-length in a number of healthy individuals with the following results: Length of the Body Pulse: in Units of 10 Cm. Estimated Observed. 80-90 90 103 90100 86 91 IOO HO 8l 87 no 120 78 84 120-130 75 78 130-140 72 76 140-150 69 74 150160 67 68 160170 65 65 170180 63 64 Over 180 60 60 As it is possible to determine the pulse-frequency from the body-length, it must also be possible to calculate the body-length from the pulse-frequency. For this purpose the following is deduced from the foregoing formula: D - DN2 D '-NT These calculations, naturally, have only a theoretical interest, and it is obvious that for purposes of comparison none but perfectly healthy individuals of the same age and sex and living under absolutely identical conditions must be selected. (c) Of other factors that influence the frequency of the pulse, it has been observed that muscular activity, heightening of the arterial blood-pressure, in- gestion of food, elevation of temperature, pain, unpleasant sensations in the alimentary tract, nausea, and psychic or sexual excitement accelerate the pulse. Further, the pulse is somewhat more frequent in the standing position (also when the body is raised passively) than in the recumbent posture. Music accel- erates the heart-beat in man and in animals and at the same time raises the blood-pressure. Exposure to increased atmospheric pressure diminishes the pulse-frequency. In the latter condition the first elasticity-elevation more nearly approaches the summit. ^ (d) The diurnal periodicity of the pulse-frequency is of especial interest. The variations rarely exceed a few beats and in a general way they correspond with the course of the temperature-curve. According to Haun the pulse is most fre- quent with the advent of winter and is least frequent with that of summer. (e) Frequency of the pulse in various animals: Elephant 28, high-bred stallion about 30 (in mares and work-horses it is a little higher), neat cattle about 50, sheep and swine 75, dog 95, cat 130, rabbit from 120 to 150 in one minute. VARIATIONS IN THE RHYTHM OF THE PULSE. 145 VARIATIONS IN THE RHYTHM OF THE PULSE (ALLORRHYTHMIA) . When the finger is applied to the normal artery no special rhythm is observed, the beats apparently succeeding one another at regular intervals, although small differences may be observed in the intervals between the 'pulse-beats; any more complicated rhythm must be considered an abnormal pulse-movement. Some- times a beat is suddenly dropped from the normal succession omission of the pulse. When this is due simply to weakness of the systole, the pulse is designated intermittent; when due to the absence of systole, the pulse is designated deficient. The latter occasionally occurs in the obese and has no pathological significance. More rarely a series of pulse-beats is characterized by the successive diminution of individual beats, followed after an interval by a return to the original strength P. myurus. Sometimes a supernumerary pulse-beat appears to be interpolated in the normal series intercurrent pulse. These forms of pulse are not infre- quently produced reflexly through the gastro-intestinal tract, or they are observed in cases of neurasthenia after psychical disturbances, often after intoxi- FIG. 52. Alternating Pulse. cation with alcohol or tobacco, in the absence of any changes in the heart. Occasionally an intereurrent systole of the auricles takes place in conjunction with the deficient or the intermittent pulse. The regular alternation from a high to a low pulse is known as alternating pulse. The peculiarity of the bigeminate pulse consists, according to Traube, in the circumstance that the pulse-beats always occur in pairs, so that the second beat always begins close to the descending limb of the curve of the first. In the same way a tr {geminate or a quadri- gciuinate pulse may be produced. Knoll found in experiments on animals that these varieties of the pulse occur whenever greater resistances develop in the circulation, increasing the demands on the heart. In man also their occur- rence points to a disproportion between the strength of the heart-muscle and the work to be performed. Absolute irregularity of the heart is designated arrhythmia or delirium cordis. VARIATIONS IN THE STRENGTH, THE TENSION, AND THE VOLUME OF THE PULSE. The relative strength of the pulse-beat (strong and feeble pulse) may be deter- mined by observing the weight the pulse is capable of raising. For this purpose a weighted sphygmograph may be used, the pad of which is applied to a section of the artery that must be constant in extent. The writing lever naturally ceases to act as soon as the pressure on the artery exceeds the strength of the pulse- beat. The load directly indicates the strength of the pulse. According to G. v. Liebig the pulse in a man with a tendency to pulmonary tuberculosis is readily compressed (feeble) and it has at the same time a tendency to dicrotism. The pulse appears hard or soft when the artery, in conformity with the mean blood-pressure but independently of the strength of the individual beat, offers a greater or lesser resistance to the palpating finger hard and soft pulse. The pulse is said to be full when the artery is greatly distended and over- filled, irrespective of the size of the pulse itself, and empty when the artery is thin and poorly filled. In determining the tension of an artery and of the pulse, that is, whether the latter is hard or soft, it should always be noted whether the artery exhibits that quality only during the pulse-wave or also while the vessel is at rest. All arteries are harder during the pulse-beat than in their resting state, but an artery that during the pulse-beat is quite hard may during the pause between the beats appear hard, or under other circumstances soft, as, for example, in cases of aortic i n - io 146 SPHYGMOGRAPHIC TRACINGS FROM DIFFERENT ARTERIES. sufficiency, in which, after the contraction of the left ventricle, a large quantity of blood flows back into the ventricle through the leaky semilunar valves of the aorta, and the arteries consequently become relatively bloodless. The pulse-ten- sion is lowest in the standing, higher in the sitting, and highest in the recumbent position. Other things being equal, the volume of the pulse-waves may be directly determined from the size of the sphygmographic tracings. Thus, the following types of pulse are distinguished: the large and the small pulse; the unequal pulse; the extremely weak pulse, which is felt only as a succession of faint tremors (tremulous pulse); and the indistinct, scarcely appreciable pulse (filiform and insensible pulse). A large soft pulse is designated a dilated pulse; a small hard pulse a contracted pulse ; a small pulse of great frequency a vermicular pulse ; a large, hard, frequent pulse a serrate pulse; a large, extremely hard pulse a vibrant- pulse ; and a pulse that is different in two corresponding arteries on opposite sides of the body (due to stenosis, compression or kinking on one side) a different pulse. SPHYGMOGRAPHIC TRACINGS FROM DIFFERENT ARTERIES. SPHYGMOGRAPHIC CURVE FROM THE CAROTID ARTERY. (Fig. 50, I, II, III; Fig. 57, C and C t .) The ascending limb is exceedingly steep, the apex of the curve (Fig. 50, 1, P), traced with a minimum degree of friction, being pointed and prominent. The first elevation below the apex is a small one, the valve-closure elevation (Fig. I, K) ; this is due to the positive wave, which is produced during the abrupt closure of the semilunar valves at the root of the aorta and is propagated with but little loss of force into the carotid artery. Close to this elevation and visible only in curves traced with a minimum of friction is the highest elasticity- elevation, which is small (Fig. 50, II, e). Further down, but still above the middle of the descending limb, is the dicrotic elevation (R), which is usually larger and is produced by the recoil of the positive wave from the already closed semilunar valves. Relatively, that is, in comparison with the remaining portions of the curve, the dicrotic elevation is slight, in consequence of the high tension prevailing in the carotid artery. After the dicrotic elevation has been formed, the descending limb falls at first abruptly to about the upper third and from this point, in well-traced curves, the writing lever in its downward movement usually traces two more small elevations, the upper of which is an elasticity- elevation, while the lower, which under favorable conditions appears much larger (Fig. 50, III, Rj) , represents the second dicrotic elevation. We have here a true tricrotism, which is the more readily recorded in the carotid, because that artery is shorter than the arteries of the extremities. SPHYGMOGRAPHIC TRACING FROM THE AXILLARY ARTERY. (Fig. 50, IV.) The ascending limb of the curve is exceedingly steep. Not far from the apex there is a small valve-closure elevation (K) , not unlike that seen in the carotid tracing. Below the middle is found the dicrotic elevation (R), which is fairly high, higher than in the carotid tracing, because in the axillary artery the reduc- tion in arterial tension permits of a greater development of the dicrotic wave. Further down, between the apex of the recoil-elevation and the foot of the curve, two or three smaller elasticity-elevations (e e) are seen. SPHYGMOGRAPHIC TRACING FROM THE RADIAL ARTERY. (Fig. 47; Fig. 50. V-X; Fig. 57, R and R'.) The ascending limb (Fig. 50, V) is of medium height; the ascent is moderately abrupt and suggests the shape of the letter f. The apex (P) is usually well marked. Below the apex there appear, when the tension is considerable, two (V, e e) , when the tension is slight, only one elasticity-elevation (VI, IX, e). There then follows at about the middle of the descending limb the recoil-elevation (R), which is usually well marked. This is the more distinct and the better pronounced the larger the number of factors present that favor the development of the secondary wave. It is smallest when the pulse is small and hard, and the artery is greatly distended (Fig. 50, VII, R) ; larger when the tension is moderate; greatest in the SPHYGMOGRAPHIC TRACINGS FROM DIFFERENT ARTERIES. 147 dicrotic pulse. In the remaining portion of the descending limb, down to the base of the curve, two or three lesser elevations are encountered, the first two being elasticity-elevations (e e) and the lowest appreciable only in rare cases and probably indicating a second recoil-wave. The sphygmographic curve of the brachial artery at the bend of the elbow is somewhat larger, but does not differ materially from the radial curve. SPHYGMOGRAPHIC TRACING FROM THE FEMORAL ARTERY. (Fig. 50, XI, XII.) The ascending limb is steep and high; on the apex of the curve, which is quite frequently somewhat flat and broad, there is recorded the closure of the semilunar valves (K) . From that point the curve falls in an abrupt manner to about the lower third. The recoil-elevation (R) appears late after the beginning of the curve, and beyond that point the curve is interrupted in both its ascending and its descending portion by small elasticity-elevations (e e) . and Fig. 53.) pedis artery the signs indi- apparatus (the heart) are SPHYGMOGRAPHIC TRACINGS FROM THE DORSALIS PEDIS ARTERY AND FROM THE POSTERIOR TIBIAL ARTERY. (Fig. 50, XIV, XV.) (Fig. 50, XIII, In the sphygmographic tracing from the dorsalis eating the great distance from the wave-producing obvious. Thus, the ascending limb of the curve exhibits a gradual ascent and is low, while the re- coil-elevation takes place late. In the descending limb two elasticity-elevations are found so near the apex (Fig. 50, e e x ) that the upper one usually occupies a point close to the latter. The elasticity- elevations in the lower portion of the descending limb are, as a rule, poorly developed. The tracing from the posterior tibial artery in many respects resembles the preceding, especially with regard to the time-relations. The tracing shown in Fig. 53 was taken from a medical student, whose height was 180 cm., with the aid of the angiograph, a moderate weight being used and the tracing being recorded on a tablet attached to a vibrating tuning-fork. FIG. 53. Tracing from the Pos- terior Tibial Artery, Recorded on the Tablet Attached to a Vi- brating Tuning-fork by means of Landois' Angiograph. By measurement it is found that 1-4 1-6 9-5 . 20 3 -5 ,61 One vibration is equivalent to 0.01613 second = 0.153 second = o-3 2 3 = 0.492 = 0.984 PHENOMENA OF ANACROTISM. As a rule, the ascending limb in the sphygmographic tracing presents the shape of the letter f, with a rather abrupt rise. The pulse-beat throws the arterial wall into elastic vibration, as has been explained, the number of vibrations de- pending largely upon the degree of arterial tension. In general the distention of the artery, or the tracing of the ascending limb of the curve, which is the same thing, is completed so rapidly that the time is equivalent to a single elastic vibration. The long-drawn-out f-shaped figure is practically nothing but a long-drawn-out elastic vibration. When, however, the number of elastic vibrations is small, and the evolution of the ascending limb of the curve is relatively prolonged, two long-drawn-out hump-like curves are some- times seen in the ascending limb of the tracing. A condition of this kind, however, is still to be regarded as normal. (See the elevations in Fig. 50, VIII, at i and 2 ; and at X i and 2.) If, however, a number of closely set elastic vibrations are produced toward the upper portion of the ascending limb of the sphygmographic tracing, so that the apex appears cut off obliquely from the ascending limb and indented, there results the phenomena of anacrotism (Fig. 54, a a), which, like the dicrotic pulse, belong in the domain of pathology. Anacrotism is observed: i. When the time occupied by the inflow of blood 148 PHENOMENA OF ANACROTISM. is longer than the duration of the elastic vibration, for example in cases of dilatation and hypertrophy of the left ventricle. This is illustrated in Fig. 54, A, which represents the radial curve from a patient with contracted kidney. Under such conditions the great mass of blood propelled with each systole requires an ab- normally long time to effect distention of the already greatly distended artery. 2. When the distensibility of the arterial tube is diminished, a quantity of blood, which in itself is not increased, will require a longer time to effect distention of the walls. Such a condition is observed in old persons whose arterial walls have acquired great rigidity. As cold tends to contract the arteries, so that they are reduced to a condition of diminished distensibility, it is not difficult to under- stand that the pulse is likely to assume the characters of anacrotism within an hour after a cool bath (Fig. 54, D). The carotid pulse in the rabbit becomes anacrotic after irritation of the vasomotor nerves. 3. When, owing to blood-stasis as a result of extreme retardation of the blood- current, such as occurs in paralyzed limbs, the quantity of blood injected into the arterial system with each systole is incapable of effecting normal distention of the arterial wall, anacrotic elevations are seen in the sphygmographic tracing (Fig. 54, B). 4. When, after ligation of an artery, the blood can enter the peripheral segment through the relatively small collateral circulation only within a comparatively long time, the distention of the arterial coat will be marked by several elastic vibrations. Wolff succeeded in producing these in tracings from the radial artery not yet possessing distinct anacrotic characters by applying compression above the brachial artery and thus retarding the flow of blood into the radial artery. Also in cases of aortic stenosis, a condition in which the blood can enter the arteries but slowly through the aorta, anacrotism has frequently been observed (Fig. 54, C). FIG. 54. Anacrotic Tracings from the Radial Artery: a a, anacrotic notches. In the same category belongs also the phenomenon of the so-called recurrent pulse. When the radial artery is compressed at the wrist, the pulse at once reappears at a point situated peripherally from the site of compression, being transmitted by the arterial palmar arches. The tracing from such a pulse ex- hibits anacrotism and in addition (as is readily understood) a diminished recoil-elevation, as well as more numerous and more distinct elasticity- elevations. 5. A peculiar form of anacrotism is observed in connection with high grades of aortic insufficiency. The most characteristic sign of this lesion is the permanent patency of the aorta. Hence, not only will waves be propagated in the root of the aorta by the movements of the ventricle, but also the contraction of the hypertrophied left auricle will cause a wave-movement in the ventricular blood that is at once propagated through the patulous orifice of the relatively flaccid aorta and its branches. This is followed by the true pulse- wave, which is pro- duced by the contraction of the ventricle. It is obvious that not only is the wave produced by the contraction of the auricle smaller, but it also precedes the principal wave. The peculiarity of the anacrotism in sphygmographic tracings from large vascular trunks, taken from cases of insufficiency of the aortic valves, is that the auricular wave occurs before the ventricular wave in the ascending limb. This anacrotism manifests itself in curves taken from the larger vascular trunks because the wave, in itself but small, gradually disappears as it advances peripherally toward the smaller vessels. Fig. 55, I, represents a sphygmographic tracing from the carotid of a man. It exhibits an abrupt ascending limb, caused by the force of the hypertrophied heart. At the apex of the curve there appear quite constantly two sharp inden- tations, the more anterior of which, having a narrower base, requires less time for INFLUENCE OF THE RESPIRATORY MOVEMENTS. 149 its development than the second. The anterior (A) is the anacrotic auricular wave, the second (V) the ventricular wave. Fig. 55, II, represents a sphygmographic tracing from the subclavian artery of the same individual. It is recognized at once by the peculiarity that the anacrotic notch (a) occupies approximately the junction of the lower and middle thirds of the ascending limb. The recoil-elevation (R) in this curve also is rela- tively small, for the same reason as in the carotid curve. Below the recoil-eleva- tion are seen feebly developed elasticity-elevations. Tracings from the femoral artery made with a minimum of friction on the part of the writing stylus exhibit an indentation (Fig. 55, III, a) immediately preceding the ascending limb of the curve, which is blurred in coarse curves. A comparison of this indentation with the anacrotic notch at the lower portion of the ascending limb of the curve from the subclavian artery (Fig. II) will convince the observer that the anacrotic auricular notch must be sought in this well-marked elevation. It should be mentioned at this point that sphygmographic tracings from cases of aortic insufficiency are characterized further by the following peculiarities: FIG. 55. I, II, III, Curves Exhibiting Anacrotic Elevation, a, in Association withflnsufficiency of the Aortic Valves. i , the great height of the curve ; 2 , the rapid fall of the writing lever from the apex. Both of these peculiarities are due to the fact that a large quantity of blood is thrown into the arteries by the enlarged and hypertrophied ventricle, a considerable portion of which flows back into the ventricle after the completion of the systole. In accordance with observations i and 2 the pulse is therefore a quick one. 3, A distinct notch is not rarely found at the apex representing an elastic vibration of the greatly distended arterial wall. 4, In tracings taken from cases of aortic insufficiency, as, for example, in that shown in Fig. 55, I, the recoil-elevation (R) is moderate as compared with the size of the curve, because, owing to the lesion of the aortic valves, the pulse-wave in its recoil does not impinge upon a suffi- ciently large surface. When the destruction of the semilunar valves is considerable, the recoil-elevation must be produced by the impact of the recurrent wave against the opposite ventricular wall. Below the recoil-elevation the curve presents two or three faintly marked elasticity-oscillations (i, 2, 3). The enormous height of the entire curve is sufficiently explained by the massive column of blood injected into the arterial system by the greatly hypertrophied and dilated ventricle. INFLUENCE OF THE RESPIRATORY MOVEMENTS ON SPHYG- MOGRAPHIC TRACINGS. The respiratory movements exert a distinct influence on the move- ments of the pulse by virtue of two different factors: (i) the purely physical diminution of arterial pressure that accompanies each inspira- tion, and the increase attendant upon each expiration; (2) the variations in blood-pressure, due to excitation of the vasomotor nerve centers, which attend the respiratory movements. 150 INFLUENCE OF THE RESPIRATORY MOVEMENTS. When it is remembered that during inspiration, owing to the dila- tation of the thorax, the arterial blood is retained in larger quantities within the chest-cavity, while the venous blood is more actively drawn into the right auricle by aspiration, it is evident that the tension within the arteries must at first dimmish during inspiration. The expiratory diminution in the size of the thorax, on the other hand, favors the flow of arterial blood into the vascular trunks and dams the venous blood back toward the venae cavae, two factors that tend to heighten the tension in the arterial system. Furthermore, the expiration that immediately precedes an inspiration allows less blood to enter the heart, so that systolic contractions at the beginning of inspiration throw a somewhat smaller quantity of blood into the aorta; the opposite result attends the inspiration that immediately precedes an expiration. These variations in tension explain the differences in the size of sphygmographic tracings taken during inspiration and during expira- tion, as seen in Fig. 56, and in Fig. 50, I, III, IV, in which / indicates the inspiratory, and E the expiratory curve. The differences are as follows: (i) the greater tension in the arteries during expiration causes a general heightening of the level of all curves coinciding with expira- tion; (2) during expiration the ascending limb is prolonged because the expiratory movement of the thorax tends to increase the force of the wave produced during expiration; (3) the magnitude of the recoil-ele- vation must be less on account of the increase in pressure during ex- FIG. 56. Influence of Respiration on the Sphygmographic Tracing (after Riegel). piration; (4) for the same reason the elasticity-elevations are more distinct and approach more nearly the level of the apex of the curve. During the stage of expiration the pulse is somewhat more frequent than during the stage of inspiration. This purely mechanical effect of the respiratory movements is modi- fied by the stimulation of the vasomotor center that takes place at the same time. Owing to this nervous influence the arterial pressure which, it is true, is lowest during inspiration begins to rise during inspiration and continues to increase until the end of that phase, reaching its maximum at the beginning of expiration. During the remainder of expiration the blood-pressure falls, and again reaches its lowest level at the beginning of inspiration. These influences leave their imprint upon the sphygmographic curves, which, accordingly, present the signs of increasing or diminishing arterial tension, in accordance with the phases of respiration. There is thus to a certain extent a displace- ment of the pressure- curve to correspond with the respiratory curve. The statements of different observers vary with regard to the effect of strong expiratory pressure and of forced inspiration on the shape of the pulse- waves. The simplest way of producing strong expiratory pressure is by means of Valsalva's experiment. During this procedure there is at first an increase in the blood-pressure, with the formation of pulse-waves resembling those produced during ordinary expiration INFLUENCE OF THE RESPIRATORY MOVEMENTS. 151 the recoil-elevation particularly being distinctly less pronounced. If, however, the forced pressure is maintained, the sphygmographic curves begin to exhibit signs of diminished tension. This is due to the influ- ence of the vasomotor center, acting reflexly through the pulmonary nerves. It must be assumed that forced pressure such as is produced in Valsalva's experiment when continued, exerts a depressing effect on the vasomotor center. Coughing, singing, and reciting act in a manner similar to Valsalva's experiment; the pulse-frequency being at the same time increased. On the conclusion of Valsalva's experi- ment the blood-pressure rises until it exceeds the normal by almost as much as it had before been diminished, to return again to the normal after a few minutes. Conversely, when the circulation is more completely emptied by means of J. Miilier's experiment, the sphygmographic curve at first exhibits the characteristic signs of diminished pulse-tension, particularly a higher and more distinct recoil-elevation. After a time, however, FIG. 57. The Effect of Marked Expiratory and Insoiratory Pressure on Sphygmographic Curves: C and R, tracings made from the carotid (C) and the radial (R) during Miilier's experiment; Q and Rj, similar tracings made during Valsalva's experiment. The curves were recorded on a tablet attached to a vibrating tuning- fork. likewise owing to nervous influences, increased tension may manifest itself. In Fig. 57, C and R represent carotid and radial curves recorded during Miilier's experiment, in which the great recoil-elevation clearly shows the diminished tension in the vessels; C l and Rj represent curves taken from the same individual during Valsalva's experiment and clearly show the opposite condition. Expiration into a vessel like a spirometer (Waldenburg's respiratory apparatus, for example) filled with compressed air has the same effect as Valsalva s experi- ment, causing after a time a slight lowering of the blood-pressure and a simulta- neous increase in the frequency of the pulse. Conversely, inspiration of rarefied air from the same apparatus acts like Muller's experiment, heightening the effect of inspiration, and it may after a time increase the blood-pressure, which, as the experiment is continued, may remain high or fall again. Inspiration of compressed air lowers the mean blood-pressure, and the after- effect is maintained. The pulse during and after the experiment is increased in frequency. Expiration into rarefied air increases the blood-pressure. These last-mentioned alterations emanate from the nervous system; they are not produced as readily and are not equally marked in all individuals. Exposure to compressed air (in the pneumatic chamber) lowers the pulse- curve: the elasticity-oscillations become correspondingly more distinct, as the recoil-elevation diminishes and finally disappears. At the same time the heart's 152 INFLUENCES OF PRESSURE ON SPHYGMOGRAPHIC TRACINGS. action becomes slower and the blood-pressure is raised. Exposure to rarefied air has the opposite effect as the sign of diminished tension in the arterial system; but only when as a result the breathing is enfeebled and the pulse is accelerated. Pathological. In the presence of adhesions between the heart and the large blood-vessels, on the one hand, and the surrounding structures on the other, the FIG. 58. Paradoxical Pulse (after Kussmaul). pulse may be much diminished in size and otherwise altered during inspiration r or it may even disappear altogether. This phenomenon has been called the paradoxical pulse. It is due to flattening of the subclavian artery in consequence of elevation of the first rib. Varieties of this pulse can be produced also in healthy individuals by voluntary alteration of the breathing during inspiration. THE INFLUENCES OF PRESSURE ON THE SHAPE OF SPHYG- MOGRAPHIC TRACINGS. The changes induced in the movement of the pulse by increasing the pressure upon it affect both the shape of the sphygmographic curves and their time-rela- tions. Fig. 59 shows at a, b, c, d and e a series of radial curves; a was taken with a minimal pressure and the remainder with a pressure of 100, 200, 250 and 450 grams respectively. The curves A and B, on the other hand, show the time-relations of curves taken when the pressure was progressively increased. A study of these curves yields the following results : FIG. 59. Variations in the Shape of Sphygmographic Curves Produced by Increasing the Pressure. 1. With a small load the recoil-elevation is relatively indistinct; the entire curve appears high. 2. With a moderate load, about from 100 to 200 grams, the recoil-elevation is most distinct; the entire curve appears somewhat smaller. 3. As the load is increased, the height of the recoil-elevation diminishes. 4. The smaller elasticity-oscillation immediately preceding the recoil-elevation manifests itself only when the load becomes considerable (from 200 to 300 grams). 5. The quickness of the pulse varies as the load is increased, the time required for the development of the ascending limb being shortened, and that required for the descending limb prolonged. 6. The height of the entire curve diminishes as the load increases. These points sufficiently emphasize the importance of taking the load of the registering instrument into consideration and the necessity of indicating the actual VELOCITY OF PROPAGATION OF PULSE-WAVES. 153 weight employed, in order to form a correct interpretation of the shape of the pulse-waves. It appears from an examination of the radial curves A and B, the former of which was taken with a weight of 100 grams, and the latter with a weight of 220 grams, from the same individual and at the same time (i vibration = 0.01613 second) , that changes in the load may produce differences also in the chronological develop- ment of the sphygmogram. When the pressure on an artery is continued for a considerable period of time, the force of the pulse gradually increases. If the greater load is then removed and a smaller one substituted, the sphygmographic curve not infrequently assumes the form of a dicrotic pulse-wave and the recoil-elevation becomes distinctly marked. During the high pressure the blood is forced to make a passage for itself by dilating the collateral vessels. If, then, the main channel is again thrown open, the entire bed of the stream, of course, suddenly becomes much wider. In consequence, there results a greater development of the recoil-elevation. Tracing X in Fig. 50 represents such a dicrotic series, taken after the application of a heavy weight. VELOCITY OF PROPAGATION OF PULSE-WAVES. As the pulse-wave passes from the root of the aorta into all the arteries toward the periphery, the pulse is felt earlier in the arteries nearer the heart than in those at a greater distance. This phenomenon was variously confirmed and variously disputed until E. H. Weber determined the movement of rapidity of the pulse- wave from the difference in time of the pulse in the external maxillary artery and in the dorsalis pedis artery and found it to be 9.240 meters in a second. With such great velocity of the pulse-wave, says this investigator, it cannot be regarded as a short wave traveling along the arteries, but so long that a single pulse-wave cannot find room in the entire distance from the beginning of the aorta to the artery of the big toe. PROPAGATION OF PULSE-WAVES IN RUBBER TUBES. As it is possible by the intermittent injection 6f water into rubber tubes to produce waves similar to those produced by the pulse, it is important to learn the results that have been obtained from a study of this undulatory movement. According to E. H. Weber, the propagation-velocity of these waves is 11.259 meters in one second. Positive and negative waves are propagated with equal velocity and the velocity of the waves is the same whether they have been pro- duced slowly or rapidly. 2. According to Bonders, the velocity of the waves is directly proportional to the coefficient of elasticity of the walls of the tubes. It is proportional to the square root of the coefficient of elasticity of the walls of the tubes, with the same lateral pressure. 3. The velocity of the waves increases with the thickness of the walls; it is proportional to the square root of the thickness of the walls, with the same lateral pressure. 4. The velocity is inversely proportional to the square root of the diameter of the tubes, the pressure remaining constant. 5. According to Marey, the velocity diminishes as the specific gravity of the fluid increases. It is inversely proportional to the square root of the specific gravity. Experiments with Rubber Tubes. In determining the time-relations Landois employed the following method. He recorded the waves by means of the angio- graph on a recording surface attached to a vibrating tuning-fork (Fig. 60). After measuring a certain distance on a long rubber tube, the extremities a and b are placed under the pad of the sphygmograph . B is a compressible bulb, by com- pression of which a positive wave is thrown into the tube, Q is a portable mercu- rial manometer, which indicates the pressure in the apparatus. As the pulse- wave first passes through at a and then at b, two elevations, i and 2, are recorded. Each small indentation is equivalent to 0.01613 second. The time-relations can be determined by simply counting these indentations. Propagation-velocity of Water-waves and Mercury-waves within Elastic Tubes. Landois' experiments, published in 1879, yielded a propagation-velocity of 11.809 meters in i second, with an internal pressure of 75 millimeters of mercury. 154 PROPAGATION-VELOCITY OF THE PULSE-WAVES IN MAN. Landois was unable to find any difference in the propagation-velocity whether the waves were produced rapidly or slowly, or whether they were large or small. In order to determine whether the material of which the elastic tube is made has any influence on the propagation- velocity of pulse- waves, Landois employed a rather rigid, slightly distensible tube made of gray vulcanized rubber. It was found that the propagation-velocity of the waves in this tube is greater than in a softer and more distensible elastic tube. This observation is in accord with the fact that the intravascular pressure FIG. 60. Method of Recording the Pulse-curves Obtained from an Elastic Tube on a Tablet Attached to a Vibrat- ing Tuning-fork. Each indentation is equivalent to 0.01613 second. exerts a demonstrable influence on the propagation- velocity of the pulse- waves; for when the pressure was raised, the waves were propagated with a somewhat diminished velocity. This phenomenon is due to the fact that the distensibility of rubber tubes increases with the pressure, whereas in the arteries the distensibility of the walls diminishes under the same conditions. The influence exerted by the specific gravity of the fluid was determined by Landois for mercury, the waves of which move with about one-fourth the velocity of waves produced in water. PROPAGATION- VELOCITY OF THE PULSE-WAVES IN MAN. Method of Examination. Landois attached to two different arteries long levers consisting of reeds and so arranged that they both recorded their pulse- curves simultaneously on the same recording surface attached to a vibrating tuning- fork. A quick tap on the fork noted the identical moment on both curves, and by counting the indentations from this point to the beginning of each curve the difference in time was obtained. In this way Landois developed the following values from a student 174 cm. PROPAGATION-VELOCITY OF THE PULSE-WAVES IN MAN. 155 in height: The difference between the carotid and the radial was 0.074 second (the distance being estimated as 62 cm.) ; between the carotid and the femoral, 0.068 second; between the femoral (at the fold of the groin) and the posterior tibial, 0.097 second (the estimated distance being 91 cm.). Results.' The foregoing observations yield a propagation-velocity for the pulse- waves in the distribution of the arteries of the upper extremities of 8.43 meters in i second, and for the arteries of the lower extremities 9.40 meters in i second. It appears that in the less distensible arteries of the lower extremities the propagation-velocity is greater for the same distance than in the arteries of the upper extremities. For the same reason it is less in the peripheral arteries and in the more yielding arteries of the child. Modifying Influences. Increase in blood-pressure accelerates, reduction in blood-pressure diminishes, the propagation-velocity of the pulse-wave. Hence, in animals, hemorrhage, slowing of the heart-beat through stimulation of the vagus, division of the spinal cord, dilatation of the vessels (by heat, profound morphin- narcosis or amyl nitrite) cause retardation; while, on the other hand, irritation of the spinal cord causes an acceleration in the movement of the pulse-wave. The length of the pulse-waves is found by multiplying the time occupied by the entrance of the blood into the aorta, which is from 0.08 to 0.09 second, by the propagation- velocity of the pulse-waves. A more convenient method is to apply the two tambours of Brondgeest's pan- sphygmograph (Fig. 44) to the two points on the artery to be examined and have one writing-lever record its tracing above that of the other on a plate at- tached to a tuning-fork. The method may be made quite trustworthy by con- structing both apparatus with leaden pipes and filling these with water, in which the propagation of the pulse-wave is quite uniform. A short tap on the tuning- fork (at points indicated by the arrows in Fig. 61) marks the identical instant FIG. 61. Tracings from the Carotid and Posterior Tibial Arteries, Made Simultaneously with Brondgeest's Pan- sphygmograph on a Tablet Attached to a Vibrating Tuning-fork. The arrows indicate identical moments. in the two curves. The difference in time is determined by simply counting the vibrations. Fig. 61 shows the curves from the carotid and the posterior tibial taken at the same time from a tall healthy student. The time-difference is 0.137 second. If the arteries are widely separated or if the observation is made on the heart and on an artery, it is possible to connect the two pads by means of a forked tube with a single writing-lever, and the two pulse-curves, when traced one into the other, can be recognized in the sphygmogram. In Fig. 62, A is the curve of the ulnar artery, B the same, together with the curve produced by the contraction of the ventricle v H p running through it, and obtained by means of a forked tube. In the curve B, H indicates the apex of the ventricular contraction, P the primary pulse-apex of the ulnar curve; v indicates the beginning of the ventricular contraction, p that of the ulnar pulse. t appears from these curves that the interval between the beginning of the ventricular con- traction and the beginning of the pulse in the ulnar artery, in the individual examined, was equivalent to 9 vibrations =0.15 second. Grashey applied two sphygmographs to two different arteries and caused the writing-levers to strike sparks into their respective curves from a spark-inductor, so that the sparks marked the identical instant of time in each curve. way he determined the propagation-velocity (from the difference between the radial pulse and that of the dorsalis pedis) to be 8.5 meters in i second. Pathological. In cases presenting diminished elasticity of the arteries, as, for 156 OTHER PULSATORY PHENOMENA. instance, due to calcification, the propagation of the pulse-wave must be more rapid. Local dilatation of the arteries, such, for example, as has long been known in the form of aneurysms, cause a retardation of the pulse-wave ; local steno- sis has a similar effect. Relaxation of the vessel-walls during high fever retards the movement of the pulse- wave. In Accordance with what has been said concerning the course of the recoil- wave, its time of appearance must also be affected by the differences mentioned. FIG. 62. Tracing from the Ulnar Artery on a recording surface Attached to a Vibrating Tuning-fork (i = 0.01613 sec.): P, the apex of the curve; e e, elasticity- vibrations; R, recoil-elevation; B, curves from the same ulnar artery, taken at the same time with v H P = the ventricular contraction of the same individual. It must appear earlier when the blood-pressure is raised, and also in atheromatous than in healthy arteries; but relatively late in the elastic arteries of the child. The latter point was determined by Landois by mensuration. While in a man, 30 years of age and 172 cm. in height, the apex of the recoil-elevation was reached 0.387 second after the beginning of the radial curve, Landois found that the apex in a girl, 8 years old and 103 cm. in height, occurred at the end of 0.387 second, evidently indicating a relative delay. OTHER PULSATORY PHENOMENA. Oral and Nasal Pulse; Tympanic Pulse. In consequence of the pulsatory movement in the arteries of the soft tissues, the air contained within the oral and nasal cavities is also set into pulsating movement when the glottis is closed, and which can be registered with the aid of the cardiopneumograph. The tracings obtained in this way, and which must closely resemble the sphygmographic tracings from the carotid artery, are of course relatively small, but they can be made larger by increasing the force of the heart. This pulse may be considerably intensified in the presence of pathological enlargement of the heart, dilatation of the left ventricle and thickening of its walls. If a ring containing a soap- bubble be inserted hermetically between the lips, the light-reflex in the bubble (seen in a mirror) reproduces almost perfectly the oscillations of the oral pulse. As a result of the systolic swelling of the vascular soft parts in the tympanic cavity analogous pulsation may be observed in the intact drumhead, or possibly in small bubbles of froth accidentally adherent to openings in a perforated membrane. If the visual field be darkened, each pulse-beat during violent exertion is often accompanied by a pulsatory illumination. Conversely, if the visual field be brightly illuminated, a corresponding obscuration of the field may take place. Pulsation is sometimes observed in the retinal arteries with the ophthalmoscope, especially in cases of aortic insufficiency. The orbicularis palpebrarum muscle under similar conditions contracts syn- chronously with the pulse. This contraction appears to be due to the fact that the beat of the pulse excites the sensory nerves and reflexly causes a contraction. In this connection attention should be called to an observation made by the brothers Edward and William Weber, which seems to be in accord with this point. They found that, in walking, the pulse and the step not infrequently coincide. Landois believed that this phenomenon may be explained by assuming that the pulse-beat stimulates the muscular mass of the thigh into contraction, to which gradually all the muscles of the thigh accommodate themselves at each step. As the blood-vessels dilate while the muscles are contracting and the movement of the venous blood is accelerated, the coincidence of pulse and step has the addi- tional advantage that the mass of blood to be moved, which is greater during the pulse-beat, is thereby better enabled to pass through the masses of muscle-tissue. VIBRATION OF THE BODY DUE TO ACTION OF THE HEART. 157 When the legs are crossed, the pulse-beat and the recoil-elevation are dis- tinctly recognized in the supported limb. If with the body at rest in the recumbent position the lower and upper incisors are brought gently in contact and kept so, a double beat of the teeth against each other will become audible, as the pulse-wave in the facial arteries elevates the lower jaw. The rapidly succeeding second impact is not due to the recoil- elevation, however, but to the concussion produced by the closure of the semilunar valves. A pulsatory movement is communicated to the brain by the large arteries at its base and in which all the individual features of sphygmographic tracings made from the cerebral arteries are recognized. Among the pathological phenomena of the arterial pulse must be mentioned the systolic pulsations in the epigastrium, which are produced in part by the heart in cases of hypertrophy of the right or left ventricle when the diaphragm is depressed, and in part by the forcible pulsation of the abdominal aorta or of the celiac axis, which is usually dilated under such conditions. Abnormal dilata- tions (aneurysms) of the arteries also occasion abnormally strong pulsations in other situations, as, for example, in the trachea in cases of aneurysm of the ascend- ing or transverse position of the aorta. Hypertrophy and dilatation of the left ventricle may cause marked pulsation in the arteries lying nearest the heart. In the presence of similar conditions in- volving the right ventricle the pulsation of the pulmonary artery in the second left intercostal space is intensified and becomes both visible and palpable (Fig. 34). In cases of aortic insufficiency with good compensation in vigorous individuals when the spleen is swollen and palpable (acute infection), this organ also pulsates. Pulsation is visible also in the penis. In cases of exophthalmic goiter the spleen may pulsate for months. VIBRATION OF THE BODY DUE TO THE ACTION OF THE HEART AND THE COURSE OF THE BLOOD-WAVES. The movement of the heart and of the pulse communicates a vibration to the body as a whole. When a person stands erect on the platform of a spring- scales, the pointer instead of assuming a position of rest plays up and down in accordance with the phases of the heart's action. In his observations (Fig. 63, I) Landois employed a low box open at the top (K), with a number of rubber bands, close together, stretched across, not far from one of the narrow sides at a b. A quadrangular board (B) was then placed with one extremity resting on the rubber bands and the other on the narrow edge of the box. The subject to be experimented with (A) takes his position on this board and stands erect and steady. In order to determine the cause of the individual indentations in the curve, the vibration-curve and the curve of the apex-beat were recorded at the same time for the same individual. For this purpose one box (p) of Brondgeest's pan- sphygmograph (Fig. 44) is applied to the vibrating board, and the pad of the other box to the situation of the apex-beat in the person to be examined. Both writing-levers record their curves on the plate attached to the vibrating tuning- fork: the upper is the vibration-curve, the lower the curve of the apex-beat. As it is impossible to exclude the marked vibrations in the apparatus itself, the information obtained with regard to the mode of production of the vibrations is only approximately accurate. At the instant of ventricular systole there occurs a short depression, corresponding to the greater pressure of the body on the elastic support ; then the body rises suddenly in response to the upward impulse of the blood- wave in the carotid and subclavian arteries. After the closure of the semilunar valves, which is registered by a slight elevation, the blood-wave, as it courses down the body again, causes increased pressure on the platform. The upward movement that now follows may be due to the centripetal wave that precedes the dicrotic wave. The number of inertia-oscillations of the vibrating base that take place until the next heart-beat will depend on the duration of the individual heart-beats. Pathological. In cases of insufficiency of the aortic valves the vibration com- municated to the body by the action of the heart is marked (Fig. 63, III). The highest apex of the curvet as well as the characteristic drop immediately preceding the ascending limb, corresponds to the ventricular systole. Below the apex of the 158 THE MOVEMENT OF THE BLOOD. highest elevation is a small notch, which is produced by a slight vibration com- municated to the blood by the partly destroyed semilunar valves in their ineffective effort at closure. The enormous wave of blood that passes through the descending aorta to the iliac artery after the closure of the semilunar valves is the cause of FIG. 63. I. Elastic Platform for Registering Vibration-curves. II. Vibration-curves Taken from the Body of a Healthy Individual. III. Vibration-curves Taken from a Man Suffering from Aortic Insufficiency and a High Degree of Cardiac Hypertrophy. the lowest drop of the elastic platform. This is followed by a rise caused by the centripetal movement of the wave. The third rise, which then follows and which is relatively low, appears to correspond with the development of the dicrotic wave in the portion of the arterial system that is directed downward. THE MOVEMENT OF THE BLOOD. The closed system of blood- vessels with its many branches, endowed as its walls are with elasticity and contractility, is not only completely filled with blood, but it is in fact overfilled. The volume of the entire mass of blood slightly exceeds the available space within the entire vascular system. It follows, therefore, that the mass of blood everywhere exerts a pressure on the vessel-walls that causes a corresponding distention of the elastic coats. This is true, however, only during life. After death the muscles of the blood-vessels relax and blood-plasma escapes into the tissues, so that the vessels after death are found partially empty. If the volume of blood be conceived as equally distributed in the entire vascular system, and as everywhere subject to the same pressure, it would be in a condition of passive equilibrium, as is the case shortly before death. If, however, the pressure to which the blood is subjected be heightened at one point of the system of tubes, the blood will escape from this point of increased pressure to some point where the pressure is less; the movement (displacement of the blood-column) is, therefore, the result of the existing difference in pressure. If the venae cavae or the aorta in a living animal be suddenly occluded, the blood will continue to flow at a gradually diminishing rate until the differences in pressure in the entire circulation have been equalized. The velocity of the blood-stream is directly proportional to the THE MOVEMENT OF THE BLOOD. 159 difference in pressure and inversely proportional to the resistance en- countered by the blood-current. The difference in pressure that produces the movement of the blood is created by the heart. In the greater as well as in the lesser circulation the point of highest pressure is at the root of the arterial system, and the point of lowest pressure at the terminal portions of the veins. Hence, the blood, constantly flows from the arteries through the capillaries and into the large venous trunks. The heart maintains the difference in pressure necessary for the circulation of the blood by throwing a certain quantity of blood into the root of the aorta at each systole, after first withdrawing a like quan- tity of blood from the terminations of the venous trunks by means of the diastole of the auricles. To these laws relating to the causes of the movement of the blood- mass, and which were formulated chiefly by E. H. Weber, must be added an important one by Bonders. That investigator demonstrated that the heart, by the work it performs, not only produces the difference in pressure necessary for the movement of the blood, but it also increases the mean pressure existing in the circulatory system. The terminal portions of the large veins that empty into the heart are larger and more elastic than the initial portions of the arteries; and if the heart transfers the same mass of fluid from the veins into the beginnings of the arteries, the arterial pressure must be increased in greater degree than the venous pressure is diminished, and the pressure as a whole must be raised. The movement of the blood-mass would be jerky or intermittent ( i ) if the walls of the tube were rigid ; for pressure exerted on the fluid contained in rigid tubes is propagated at once throughout the entire length of the tubes, and the movement of the fluid ceases simultaneously with the impact that causes the increase in the pressure. (2) The move- ment would be intermittent also within elastic tubes if the interval between two successive systoles were longer than the duration of the movement of the column necessary to equalize the difference in pressure produced by the systole. If, however, this interval is shorter than is necessary for equalizing the pressure, the current becomes continuous. The more rapidly systole follows upon systole, the greater will be the difference in pressure, the elastic walls of the arterial tubes at the same time undergoing greater distention. In the continuous current thus produced the sudden increase in pressure caused by the systolic injec- tion of a mass of blood corresponding to the size of the ventricular cavity can always be recognized as an intermittent, jerky acceleration of the current (pulse). This intermittent acceleration of the current is propagated along the arterial pathway with the velocity of the pulse- wave, as both are due to the same cause. Each pulse-beat is therefore attended with a tem- porary, rapidly advancing acceleration of the fluid-particles. Just as the form of the pulse-movement, however, is not simple, so also is this pulsatory acceleration of the current not simple. The latter appears in the complicated form of the current pulse-curve, which likewise exhibits the primary elevation and the recoil-elevation like a (pressure-)sphygmo- graphic curve. Every up-stroke in the limb of the curve corresponds to an acceleration and every down-stroke to a retardation of the moving particles of fluid. l6o SCHEMATIC REPRODUCTION OF THE CIRCULATION. Physical Explanation. The conditions detailed may be illustrated by means of simple physical experiments. If a rigid tube be connected with the nozzle of a syringe, every movement of the piston will be followed by an intermittent expulsion of water, which will correspond in time exactly to the movement of the piston. The effect of the intermittent injection of fluid into an elastic system of tubes is best exemplified in a fire-hose. Here the air contained in the air- chamber which is under elastic tension takes the place of the elasticity of the tubes themselves in the circulatory apparatus. With slow intermittent strokes of the pump, the stream of water is interrupted; but if the movements of the pump are more frequent, the compressed air in the air-chamber effects a continuous outflow, although a distinct acceleration of the stream is seen in correspondence with each stroke of the pump. Landois was able without difficulty to demonstrate that the particles of water in an elastic tube are set in motion during the passage of the current by every pulsatile wave, in correspondence with the picture presented by the sphygmo- graphic tracing, by introducing in the course of a long elastic tube, in which both a continuous and an undulatory movement could be produced by intermittent pumping, a short glass tube containing a thread passing through an opening in the side and floating to and fro in the stream. Immediately in front of the thread a sphygmograph was connected with the tube. Each pulse-beat caused a synchronous movement of the sphygmograph and of the thread, each upward stroke of the writing lever corresponding to a more marked oscillation of the thread toward the periphery (acceleration) , while each downward stroke was marked by a slight diminution in the oscillatory movement (retardation) . In the capillary vessels the pulsatory acceleration of the current ceases with the disappearance of the pulse-wave. The two movements are gradually extinguished by the marked resistance encountered by the blood in the capillary system. It is only when the capillary vessels are greatly dilated and the pressure in the arterial system increases that both pulse and pulsatory acceleration of the current are sometimes communicated to the initial portions of the veins through the capillaries. Such conditions are observed in the vessels of the salivary glands after stimulation of the facial nerve, which dilates the vascular channels. After constriction of the finger with an elastic band, which impedes the return flow of venous blood, and causes an increase in the arterial pres- sure, with dilatation of the capillaries of the finger, the swollen skin is seen to become intermittently more deeply red isochronously with the well-known throbbing sensation. This is the capillary pulse. Pathological. The capillary pulse is found sometimes when the action of the left ventricle is greatly increased, for example in cases of aortic insufficiency and of exophthalmic goiter, and often in cases of jaundice. SCHEMATIC REPRODUCTION OF THE CIRCULATION. The arrangement of the circulation as described permits a reproduction by physical means, of the most essential conditions, in the so-called model of the circu- lation. Weber's model will be briefly described here. The arterial system and the somewhat larger venous system are represented by portions of animal intestine (Fig. 64). The system of capillaries between the two is formed by a glass tube of sufficient size, the lumen of which, however, is occupied by a piece of sponge. A short section of intestine into each extremity of which a piece of glass tube is tied represents the heart. The glass tube directed toward the arterial trunk is provided with the necessary valves, which are reproduced by having a piece of small intestine project beyond the edges of the glass tube and securing its free margins with three threads. Through this piece of intestine water can enter only in the direction from the glass tube toward the free intestine, but not in the opposite direction, as the free edges would then come together and close the lumen. From the venous side a similar valve, mounted on the extremity of a separate piece of tube, is inserted into the glass tube directed toward CAPACITY OF THE VENTRICLES. l6l the heart. The two valves open in the same direction. The entire apparatus is moderately distended with water by means of a funnel. By compressing the heart-piece the contents are made to flow through the arterial valve into the arterial portion. When the compression ceases, the contents return from the venous portion through the venous valve into the heart. By means of this apparatus the blood-current becomes continuous when the heart is com- pressed in rapid succession, and the movement of the pulse can be demon - Arterial Valve. Capillaries. FIG. 64. Model of the Circulation by Ernst Heinrich Weber. strated. The latter does not extend beyond the capillary region because the great resistance offered by the many pores of the sponge destroys the force of the pulse-waves. More complicated models of the circulation, which, however, do not essentially illustrate more than this primitive model by E. H. Weber, have been designed by numerous investigators. CAPACITY OF THE VENTRICLES. As the heart creates the difference in pressure necessary for the circulation of the blood by throwing a definite quantity of blood into the roots of the two large arteries every time the ventricles are emptied by systolic contraction, it is desirable to determine this quantity of blood. As the right and left ventricles must contract simultaneously, and as, in addition, the same quantity of blood must pass through the lesser circulation as through the greater, it follows that the capacity of the right ventricle must be equal to that of the left. It must be remembered, however, that a moderate quantity of blood always remains in the ventricle, as this does not empty itself completely, even at the height of its contraction. Methods. i. The capacity of the ventricles is determined directly by filling the chambers of the flaccid heart after death with a coagulable material and measuring the coagulated mass. This is an uncertain method, because the pressure in the living ventricles during their diastole, following the contraction of the auricles,* is not known. 2. Indirect Estimation. A. W. Volkmann, in 1850, estimated the capacity of the left ventricle in the following manner. The cross-section of the aorta and the velocity of the blood-current in the vessel are determined. From these data the quantity of blood that passes through the aorta in a unit of time is cal- culated. As the total quantity of blood in the body (jV f the body-weight) is known, the time required for the passage of this quantity through the aorta can easily be calculated. Finally, if the number of systoles that occur during the time of circulation be known, the quantity of blood for each systole will correspond to the capacity of the ventricle. On the basis of numerous animal experiments Volkmann estimated the ventricular capacity to be equal to ^ of the body- weight; or 187.5 grams f r a rnan weighing 75 kilograms. The accuracy of this method also leaves much to be desired, because the velocity of the current in the aorta, which according to C. Ludwig and Dogiel is subject to considerable ii l62 METHODS FOR MEASURING THE BLOOD-PRESSURE. fluctuations, can only be determined approximately. Tigerstedt considers Volk- mann's figure much too high. He determined the quantity of blood expelled by the left ventricle with each systolic contraction in the rabbit by introducing in the continuity of the aorta an instrument resembling a current-meter. From animal experiments he estimates that in man only 69 cubic centimeters are ex- pelled at each ventricular contraction. Place calculated as follows: A man uses about 500 liters of oxygen in 24 hours. In order that the venous blood, which contains on the average 7 volumes per cent, less of oxygen than arterial blood, may take up this quantity of oxygen, about 7000 liters of blood must be driven through the lungs in 24 hours. Allowing 100,000 heart -beats for the 24 hours, only 70 cubic centimeters are propelled with each systole. Other more recent investigators also have calculated that the quantity of blood expelled with each systole is equal only to $ of the capacity of the dead ventricle, or 60 cubic centimeters. METHODS FOR MEASURING THE BLOOD-PRESSURE. A. In Animals. i. Hales' Tube. Stephen Hales, in 1727, first fastened a long glass tube in the lateral wall of a vessel and determined the blood-pressure by measuring the height of the vertical column of blood in the tube. Hales' tube was fitted at its lower extremity with a short copper tube, bent at a right angle and directed toward the heart ; it therefore really represented a so-called Pitot's tube. Pitot, in 1731, used a similar tube to determine the velocity of the current in rivers. The water entering the horizontal portion of the tube, which is directed up-stream, rises in the vertical portion, which projects above the water, to a level proportional to the velocity of the current. This level represents the "velocity-altitude" and it indicates that the water flows with a velocity equivalent to that attained by a body falling freely from a height equal to the velocity-altitude. If a Pitot tube (Fig. 70, II, o p x) be introduced into a closed tube through which flows a fluid under pressure, and an ordinary manom- eter (x y) be introduced at the same time, the latter will register only the tension of the wall; but in a Pitot tube the fluid will rise to a higher level, for this column of fluid indicates not only the tension of the blood, but also its velocity-altitude. In arteries, however, the latter is extremely small as compared with the former. 2. Poiseuille's Hematodynamometer. Poiseuille, in 1828, used a U-shaped man- ometer-tube filled with mercury, which he inserted laterally by means of a rigid connecting piece into the wall of the vessel. A I shaped tube may also be used to connect the blood-vessel with the manometer, the short continuous extremities being inserted into the open vessel (Fig. 65, I, a a) and the vertical limb being connected with the manometer (M) by means of a leaden tube. 3. Ludwig's Kymograph. Carl Ludwig, in 1847, placed a float (Fig. 65, I, d s) on a column of mercury (as James Watt had already done for the manometer of the steam-engine) . To the float was attached a vertical wire carrying a writing- contrivance, which records not only the height of the blood-pressure, but also the variations in the pulse-waves on the drum (C) , which is made to rotate by clock- work. A. W. Volkmann gave the name of kymograph (wave-tracer) to this instrument. The difference between the levels of the mercurial columns (c d) in the two parts of the tube indicates the pressure within the vessel (the height of the column of mercury multiplied by 13.5 gives the pressure-altitude of the corresponding blood-column) . Setschenow added a stopcock at the center of the lower bend of the tube (at b) . When this stopcock is turned so as to leave only a narrow orifice of communication, the pulse-waves cease to manifest themselves and the instrument records only the mean pressure. In this form the instrument is the most reliable for this purpose. The pulsatory variations in pressure are recorded by the kymograph as simple elevations (Fig. 65, III) and, therefore, they do not in the least correspond to the curves obtained with the sphygmograph. After the mercury has once been set in motion by the pulse-beats, it simply undergoes movements up and down by virtue of its own oscillations and all the finer shades of the pulse are completely obliterated. For this reason the kymograph can be used only for recording the blood-pressure, and never for pulse-tracings. In order to determine the mean pressure from a long blood-pressure tracing presenting numerous elevations and depressions, the planimeter is employed. This instrument is carried over the entire outline of the surface occupied by the curve METHODS FOR MEASURING THE BLOOD-PRESSURE. ^3 namely the curved line, the abscissa {base) and the initial and terminal ordin obtained by counting the squares. A. W. Volkmann cut out the cuTe-ar^a and weighed it, and then compared with it the rectangle made from the and havinp- the samp Kac^-lin^ m +v,~4- ,> ~-n.:.. j_ & , 1 1 to which is frequently attached to steam-engines A hollow spring bent in the shape of the 'letter C (F) and filled with alcohol FIG. 65. I, Carl Ludwig's Kymograph; II, Adolph Pick's hollow-spring kymograph; III, blood- pressure curves (above) and respiratory curves (below), traced at the same time (after C. Ludwig and Einbrodt). is brought into connection at its lower extremity (a) with the lateral wall of the artery (x x) by means of a suitable cannula, while the other extremity of the spring is closed. As soon as the internal pressure is increased, the bent spring is straightened out. The closed extremity (b) is connected with an upright rod (g), which acts on a system of writing-levers (hike) composed of delicate pieces of reed, which records the variations in pressure on a moving recording surface. Both the blood-pressure and the variations in the pulse are recorded; the latter, however, without their characteristic peculiarities. Hiirthle reduced the apparatus to one-fourth of its original size, in which form the results recorded are quite accurate because of the slight displacement of fluid. 5. A. Pick's Flat-spring Kymograph (Fig. 66) has been used in preference to any other by its inventor since 1885. A tube, i mm. thick and filled with air (Fig. 66, a a), communicates with the blood-vessel by means of a cannula (c), and ends in an excavated expansion covered with a rubber membrane, from which a point (s) projects downward. The latter presses upon a tightly stretched hori- 1 64 METHODS FOR MEASURING THE BLOOD-PRESSURE. zontal steel spring (F), which articulates by means of a connecting piece (b) through two joints (d i} with a writing-lever (H} . The parts of the instrument are held in a metallic frame (R K). In order to determine the absolute values of variations in pressure the apparatus must first be graduated empirically by com- paring it with a mercurial manometer. 6. Hurthle's Manometer (Fig. 67) is a similar instrument. A small metallic drum (Fig. 67, d) is intercalated in the course of an artery (c c) by means of tubes. The drum is covered with a thin rubber membrane, from the center of which a process (e) projects. The latter is supported by a spring (F), to which,. Fio. 66. Adolph Pick's Flat-spring Kymograph. at some convenient point that can be varied at will (v), the writing-lever is at- tached. The whole contrivance is attached to a stationary rod (i i) by means of a carrier (T). This apparatus also, like the preceding one, must first be gradu- ated empirically in order to determine in advance the height to which the point (s) of the writing-lever gradually rises with increasing pressure (from o to 100 mm. of mercury). Hiirthle also constructed a torsion-manometer according to the plan of Rov, the pressure being measured by the torsion of a steel spring. B. In man the blood-pressure within an artery can be measured in the sim- plest manner by means of a graduated sphygmograph. The weight that just FIG. 67. Hurthle's Kymograph. suffices to arrest the movement of the writing-lever corresponds to the tension of the vessel. The radial artery of healthy students examined in this way under Landois' direction and loaded for a distance of i cm. exhibited an average blood- pressure of 550 grams. Manometric Method. v. Basch determined the blood-pressure by a mano- metric method, applying his sphygmomanometer to the pulsating vessel. The hollow, air-containing cushion applied to the artery communicates with an aneroid barometer, the pointer of which indicates the pressure. As soon as the pressure indicated by the latter slightly exceeds the pressure in the artery, the latter is THE BLOOD-PRESSURE IN THE ARTERIES. 165 compressed and pulsation beyond the point of compression is abolished. In the temporal artery the pressure is from 80 to 1 10 mm. of mercury. Both of the foregoing methods not only demonstrate the blood-pressure within the arteries, but the pressure exerted by the cushion must exceed the arterial pressure to a degree sufficient to compress the empty artery (which in itself repre- sents a gaping tube). As compared with the blood-pressure, however, the resist- ance of the artery is extremely slight, being only 4 mm. of mercury, although naturally greater in cases of arteriosclerosis. In the same way the resistance offered by the soft parts superposed upon the artery must also be overcome and in individuals of firm fiber with an abundance of fat this resistance is not incon- siderable. In this way v. Basch found in adults a pressure of from 135 to 165 mm. of mercury in the radial artery; from 80 to no mm. in the superficial tem- poral. Federn thinks it is lower, namely from 80 to 100 mm. of mercury. In children the blood-pressure increases with age, size, and weight. In the superficial temporal it was found to be 97 mm. between 2 and 3 years of age, and 113 mm. of mercury between 12 and 13 years of age. The blood-pressure rises immediately after exercise; it is higher in the recumbent than in the sitting posture, and in the latter than in the erect posture. After a cold, as well as after a hot, bath the blood-pressure is at first raised and the flow of urine is increased. Hurthle employs the plethysmograph (Fig. 73) in the following manner for measuring blood-pressure. The glass cylinder communicates with a mercurial manometer. The forearm, first rendered bloodless by firmly bandaging it, is introduced into a cylinder containing water and closed in hermetically. When the blood is allowed to flow freely into the arm, the fluid in the cylinder is dis- placed and enters the manometer. The blood continues to flow into the arm until the manometric pressure is equivalent to the blood-pressure. The mean pressure in the arm is said to be about 100 mm. of mercury. Sphygmomanometers have been constructed by Marey and Mosso on similar principles. THE BLOOD-PRESSURE IN THE ARTERIES. The blood-pressure in the arteries is quite considerable, varying within fairly wide limits. In the larger arteries of large mammals and probably also of man it is between 140 and 160 mm. of mercury. Examples : Carotid of the horse, i6imm.(Poiseuille). Aorta of the frog, 22-29mm.(Volkmann). 212-214 mm. (Volk- Brachial artery of the pike, 35-84 mm. mann) . (Volkmann) . dog, 151 mm. (Poiseuille) . Brachial artery in man (after operation) " 130-190 mm. (Lud- 110-120 mm. (Faivre) ; perhaps a wig). little too low on account of the goat, 118-135 mm. (Volk- traumatism and the disease. mann) . ' ' rabbit , 9 o mm . (Volkmann) . > " chicken, 88-171 mm. (Volk- mann) . In patients about to be subjected to amputation of the thigh E. Albert, with the aid of a manometer, found the blood-pressure in the anterior tibial artery above the ankle to be between 100 and 160 mm. of mercury. The pulsatory elevation of the column of mercury was from 17 to 20 mm. Coughing caused an increase of between 20 and 30 mm.; firm bandaging of the healthy leg an increase of 15 mm.; passive elevation of the body, in consequence of which the length of the hydrostatic column of blood was augmented, an increase of 40 mm. of mercury. The pressure in the aorta of large mammals is estimated to be between 200 and 250 mm. of mercury. In general, the blood-pressure is lower in large than in small animals because, on account of the greater length of the blood-channels, a greater resistance is to be overcome. In exceedingly young and exceedingly pic animals the pressure is lower than in individuals at the height ^of their vital In embryos the arterial pressure is scarcely one-half as great as in the new- born, but the venous pressure is greater. The difference between the arterial and the venous pressure in embryos was found to be scarcely one-half as great as in full-grown animals. l66 THE BLOOD-PRESSURE IN THE ARTERIES. Within the large arteries the blood-pressure undergoes relatively slight diminution toward the periphery, because the differences in the resistance in various sections of the large tubes are inconsiderable. As soon, however, as the arteries undergo frequent division and their caliber accordingly becomes greatly diminished, the blood-pressure rapidly diminishes, because the propulsive power of the blood is weakened by the effort to overcome the increased resistances produced in this way. The arterial pressure increases directly with the quantity of blood present in the arteries, and conversely. The pressure, therefore, Increases Diminishes 1. As the heart's action becomes stronger i. As the heart's action becomes feebler and more rapid. and slower. 2. In plethoric individuals. 2. In anemic individuals. 3. After considerable increase in the 3. After profuse hemorrhage or loss from quantity of blood by the direct in- the blood in some other way, as jection of blood, and also after cop- for example, by profuse sweating ious ingestion of food. or copious diarrhea. The increase and decrease in blood-pressure is not directly proportional to the increase and decrease in the quantity of blood. By virtue of their muscular libers the blood-vessels possess the faculty of adapting themselves within fairly wide limits to the variable volume of blood. The blood-pressure, therefore, does not rise at once when the quantity of blood is moderately increased. The cir- cumstance that fluid rapidly transudes from the blood into the tissues also assists in maintaining a constant blood-pressure. Moderate venesection, in the dog up to 28 per cent, of the body-weight, is not followed by any noteworthy diminution in the blood-pressure. After slight hemorrhages the pressure may even rise, but the removal of a large quantity of blood is followed by a considerable fall in the blood-pressure, and the loss of from 4 to 6 per cent, of the body-weight reduces it to zero. Increased pressure within the vessels produced by engorgement tends to dilate the cutaneous and muscular vessels, especially those of the extremities, and affects the arteries in the viscera but little. After the pressure has fallen, the visceral blood-vessels return to their original caliber much more promptly than do the cutaneous and muscular blood-vessels. The arterial pressure rises as the capacity of the arteries is diminished, and conversely. This is accomplished by contraction or relaxation of the unstriated muscle-fibers of the arterial wall. The pressure within a certain area of the arterial system rises or falls accordingly as the blood-vessels in neighboring areas undergo contraction or even become impermeable from compression or ligation or dilatation. The application of heat or cold to a circumscribed portion of the body, also of pressure or diminution of pressure (the latter by introducing an extremity into a closed space containing rarefied air, as, for example, Junod's cupping boot), and the effect of stimulation or paralysis of certain vasomotor areas, furnish striking proofs of the cor- rectness of this statement. The respiratory movements produce regular variations in the arterial pressure, known as respiratory pressure- variations the pressure falling with each deep inspiration and rising with each expira- tion. These variations are readily explained by the fact that at each expiration the blood in the aorta is subjected to the increased pressure of the compressed air in the thorax, while with each inspiration the blood undergoes a diminution in pressure, in consequence of the influence of the rarefaction of the air in the lungs, on the aorta. In addition, the in- spiratory expansion of the thorax tends to draw the blood from the venae cavae into the heart, while during expiration the blood stagnates, and THE BLOOD-PRESSURE IN THE ARTERIES. 167 in this way influences the blood-pressure. The changes are greatest in the arteries nearest the thorax. The respiratory variations in blood-pressure are in part dependent upon changes in the nervous impulses sent out by the vasomotor center, which coincide with the respiratory movements, and by virtue of which the arteries contract and thus increase the arterial pressure (Traube- Hering's pressure-variations). Fig. 65 III shows a respiratory curve (heavy line) and a blood-pressure curve traced at the same time. This figure shows that at the instant when expiration begins (at ex), the blood-pressure curve rises along with the expiratory pressure, and, con- versely, that both curves fall from the instant that inspiration begins (at in) ; yet the blood-pressure curve begins to rise a little earlier (at c) than expiration itself has begun, that is, during the last part of inspira- tion. This is due to the contraction of the arteries, which begins a little earlier in obedience to impulses sent out by the vasomotor center. The effect of the arterial contraction is reinforced by the circumstance that during the inspiratory stage the heart is more completely emptied on account of the increased venous flow. The respiratory variations in blood-pressure are observed also during artificial respiration ; if this be suddenly interrupted (in curarized animals), the resulting irritation of the medulla oblongata due to the dyspnea causes a considerable rise in the blood-pressure. In accordance with the depth of the respirations and the corresponding pres- sure-variations of the air within the thorax, great inequalities are observed" in the respiratory fluctuations. This is evident. from the fact that in man during quiet inspiration the diminution of pressure in the trachea is equivalent to only i mm. of mercury, while during the deepest possible inspiration (with the respiratory canal tightly closed) the diminution is 57 mm. Conversely, quiet expiration in man is attended with an increase in the pressure in the trachea of only 2 or 3 mm., while vigorous contraction of the abdominal muscles causes an increase of 87 mm. of mercury. Kronecker and Heinricius attribute the variations to mechanical causes, namely to the compression of the heart that accompanies respiration (because, according to them, rhythmical injections of air into the pericardium, which com- press the heart, also give rise to analogous variations in blood-pressure). Any interference with the diastole of the heart lowers the blood-pressure; as soon, therefore, as the lung has been distended during inspiration sufficiently to displace the heart, diastole is interfered with and the tension in the aortic system is in consequence lowered. As soon as the air can escape from the lungs and these organs contract, a greater quantity of blood enters the heart, and the arterial pressure rises. The movements of the pulse cause intermittent variations in the mean arterial pressure, the so-called pulsatory pressure-variations. The column of blood injected into the aortic system by the ventricle at each systole, acting in conjunction with the positive wave, produces an in- crease of pressure in the arterial system corresponding to this positive wave. The increase in pressure finds corresponding expression in the various elevations of the sphygmogram ; it also travels along the arteries with the same velocity as the pulse-waves. In the larger arteries of the horse Volkmann found the pulsatory increase of pressure to be T ^, and in the dog T V of the total pressure. Hurthle/with the aid of his hemodynamometer, found that the pulsatory increase of pressure in the rabbit was equal to almost one-third of the pressure during the interval between pulse-beats. None of the pressure-recording instruments described shows the form of these pressure-variations with sufficient accuracy; most of them merely record elevations l68 THE BLOOD-PRESSURE IN THE CAPILLARIES. and depressions. Hiirthle's kymograph, however, furnishes sufficiently accurate pictures of the pressure-variations in the arteries : these resemble sphygmographic tracings. Hence, the sphygmographic pulse-tracing is at the same time a faithful expression of the pulsatory variations in blood-pressure. Muscular exertion increases the blood-pressure. At the beginning of a muscular contraction the pressure sometimes undergoes a tempo- rary fall. When the heart's action is interrupted by continuous stimulation of the vagus or a high positive respiratory pressure, the blood-pressure diminishes enormously in the arteries; while, on the other hand, it increases in the venous trunks because the blood flows from the arteries into the veins in order to equalize the difference in pressure. This experi- ment shows that when the difference in pressure is (almost) abolished, the resting blood continues to exert some pressure on the blood-vessel walls ; that is, in consequence of distention with blood, even in the resting state, a lower pressure is exerted on the walls. Pathological. In man it has been found that the blood-pressure, as determined by v. Basch's method, is increased in association with chronic inflammation of the kidneys, arteriosclerosis, lead-colic, after injections of ergotin, and in cases of cardiac hypertrophy with dilatation. It is diminished in the presence of cardiac insufficiency. Digitalis often raises the blood-pressure in cases of cardiac disease ; after the injection of morphin the pressure falls. During fever the blood-pressure usually falls, as the shape of the pulse-curves also indicates; in cases of cardiac insufficiency, chlorosis and pulmonary tuberculosis the blood-pressure is also low. If the pressure falls to about 75 mm. in cases of diphtheria (children) , the prognosis is grave. THE BLOOD-PRESSURE IN THE CAPILLARIES. Method. Owing to the minute diameter of the capillaries the pressure within these vessels cannot be determined directly. By applying a small glass disc of known dimensions to the vascular substratum and weighting it in a suitable manner until the capillaries become pale, the degree of pressure that just over- comes the pressure within the capillary region is determined approximately. The calculation is made as follows : The pressure (expressed in centimeters of a column of water) is obtained by dividing the number that represents the compressing weight (weight + the weight of the glass disc) by the number of square centi- meters contained in the surface pressed upon. In the capillaries of the finger, when the hand is held up, this pressure is 24 mm. of mercury, and with the hand dependent, 62 mm. ; in the ear it is 20 mm. ; in the gums of the rabbit 32 mm. Roy and Graham Brown press the vascular area to be examined from below against a rigid glass disc by means of an elastic bladder provided with a manom- eter; the microscope can then be focused on the glass disc. The tension of the blood in the capillaries of a circumscribed area is increased by: (i) Dilatation of the small arteries supplying the area. If the latter are dilated, the blood-pressure can be propagated from the large trunks with less loss. (2) Increase of pressure in the small arteries supplying the area. (3) Constriction of the veins draining the capil- lary area. Occlusion of the veins causes a fourfold increase in the pressure. (4) Increased pressure in the veins, as, for example, by change of position (hydrostatic pressure). Diminution of the blood- pressure in the capillaries is brought about by the opposite conditions. Also, changes in the diameter of the capillaries must have some influence on the internal pressure. The inherent power of movement (movement of the proto- plasm) of the capillary cells, as well as the pressure, swelling, and consistency of the surrounding body-tissues must be considered in this connection. As the THE BLOOD-PRESSURE IN THE VEINS. 169 resistance to the blood-current is greatest in the small arteries and in the capillary system, the blood especially in long capillaries must be subject to different degrees of pressure at the beginning and at the end of such capillaries. In the middle of the capillary system the pressure may not be much less than one-half the pressure prevailing in the main arterial trunks. The capillary pressure exhibits many variations in different parts of the body. Thus, in the erect position, the pressure in the capillaries both of the intestine and of the glomeruli of the kidneys, as well as in those of the lower extremities, will be greater than in those of other regions of the body; in the former case on account of the two-fold resistance offered by the duplicate arrangement of the capillaries; in the latter case, from purely hydrostatic influences. THE BLOOD-PRESSURE IN THE VEINS. In the large venous trunks near the heart (innominate, subclavian, and common jugular veins) the blood is under a negative pressure, which is on the average equivalent approximately to o.i mm. of mercury. This enables the lymph-stream to empty itself freely into the large venous trunks. As the distance from the heart increases, the lateral pressure in the venous trunks gradually increases. In the external facial vein of the sheep it is +0.3 mm., in the brachial 4.1 mm., in branches of the brachial 9 mm.; in the femoral 11.4 mm. The following conditions influence the pressure in the veins : 1. All factors that tend to diminish the difference in pressure exist- ing between the arterial and the venous system, which maintains the circulation of the blood, necessarily increases the pressure in the veins, and conversely. 2. General plethora increases the pressure in the veins, while anemia diminishes it. 3. A special influence on the tension in the large trunks situated near the heart is exerted by the respiration; for during each inspiration the pressure diminishes and the blood rushes toward the thoracic cavity; while with each expiration the pressure increases and the blood stag- nates. This effect is intensified in proportion to the depth of the res- pirations, and when the respiratory passages are closed it must be par- ticularly great. 4. The slight stagnation of the blood in the venae cavae that accom- panies every contraction of the right auricle has already been discussed in the section devoted to the movements of the heart The respiratory, as well also as the cardiac, fluctuations can sometimes be detected in the common jugular vein of healthy individuals. 5. Changes in the position of the limbs or of the body through hydrostatic influences modify the pressure in the veins in various ways. The highest pressure is found in the veins of the lower extremities, and they are accordingly most abundantly supplied with muscle-tissue. When the muscles and valves in these veins become insufficient, dila- tation is likely to develop (varices). THE BLOOD-PRESSURE IN THE PULMONARY ARTERY. Method. Direct estimation of the pressure in the pulmonary artery was made in 1850 by C. Ludwig and Beutner, who opened the left pleural cavity and con- nected the tube of a manometer directly with the left pulmonary artery, artificial respiration being resorted to. In this way the lesser circulation of the left lung was interrupted completely in cats and rabbits and almost completely in dogs. In addition to this disturbance, the normal flow of the venous blood into the right 170 THE BLOOD-PRESSURE IN THE PULMONARY ARTERY. heart ceases as soon as the thoracic cavity is opened, because the elastic traction of the lungs is abolished and the right heart itself is exposed to the full pressure of the air. The pressure was found to be in the dog 29.6, in the cat 17.6, and in the rabbit 12 mm. of mercury (in the dog 3 times, rabbit 4 times, and in the cat 5 times less than the pressure in the carotid) . Faivre and Chauveau, in 1856, introduced a catheter into the right ventricle through the jugular vein and connected it with a manometer. Knoll reached the pulmonary artery through the anterior mediastinum, with- out opening the pleural cavities, and introduced a cannula laterally into the trunk of the vessel. By this method he was able to observe the pressure in the artery during spontaneous breathing without restricting the lesser circulation and with- out displacing the heart. He thus found a mean pressure of 12.2 mm. of mercury in the rabbit. Indirect estimation can be made by comparing either the muscular walls of the right with those of the left ventricle, or the thickness of the walls of the pul- monary artery and of the aorta, for it must be assumed that there is a definite relation between the thickness of the walls and the pressure within the vessels. Beutner and Marey estimate the relation of the pulmonary pressure to the aortic pressure as i : 3 ; Goltz and Gaule, as 2 : 5. Pick and Badoud, in the dog, found the pressure in the pulmonary artery to be 60 mm., and in the carotid in mm. of mercury. According to Knoll the pul- monary pressure in the rabbit is 6.8 times less than the pressure in the carotid. In a child the pressure in the pulmonary artery is relatively greater than in the adult. The pulmonary pressure exhibits certain rhythmical variations due to varia- tions in the tone of the heart's action. When the air-pressure in the lung falls, the pressure in the lesser circulation also falls, and conversely. The expansion of the lungs in the thoracic cavity is maintained by the nega- tive pressure on their outer pleural surface. When the glottis is open, the inner surface of the lungs and the walls of the alveolar capillaries traversing the lungs are exposed to the full pressure of the air. The heart and the large vascular trunks of the thorax, however, are subject not to the full pressure of the air, but to the pressure of the air minus the pressure corresponding to the elastic traction of the lungs. The trunks of the pulmonary artery and veins are accordingly subject to the same pressure-conditions. The elastic traction of the lungs is proportional to the degree of expansion of the lungs. The blood in the pul- monary capillaries will thus have a tendency to flow from these capillaries into the large vascular trunks. As the elastic traction of the lungs affects chiefly the more delicate pulmonary veins, and as re gurgitation of the blood is prevented by the semilunar valves of the pulmonary artery, as well as by the contraction of the right ventricle, it follows from these pressure-conditions that the capillary blood in the lesser circulation is drained into the pulmonary veins. Thin-walle'd tubes embedded within the substance of the walls of an elastic, distensible sac suffer a modification of their lumen, in accordance with the manner in which the sac is distended; for, if the sac is directly inflated so that the air- pressure in its interior increases, the lumen of the tubes is diminished; if, however, the sac is distended by rarefying the air in the closed space surrounding it, the tubes embedded in the wall dilate. When the distention is brought about in the latter way, namely by the negative pressure of aspiration, the two pulmonary sacs within the thoracic cavity are maintained in a state of distention; therefore the vessels of air-containing lung are more dilated than the vessels of collapsed lung. Consequently, more blood flows through the lungs when they are distended within the thorax than when they are collapsed. Inspiratory distention has a similar effect and increases the flow of blood. The negative pressure prevailing in the lungs during inspiration causes a considerable dilatation particularly of the pulmonary veins, into which vessels, therefore, the pulmonary blood readily flows; whereas the blood of the pulmonary artery, flowing through thick-walled trunks under high pressure, undergoes scarcely any alteration. The velocity of the blood in the pulmonary vessels is, therefore, increased during inspiration. The blood-pressure in the lesser circulation is higher also when the lungs are in a state of distention. Contraction of the vessels, which causes an increase of MEASUREMENT OF THE VELOCITY OF THE BLOOD-CURRENT. 171 pressure in the greater circulation, has the same effect in the lesser circulation because more blood flows into the right heart. The vessels of the lesser circulation are exceedingly elastic and their tonicity is slight; hence impermeability even of large pulmonary branches is readily compensated for. Forcible contraction of the abdominal muscles (straining) causes at first a marked increase in the flow of blood from the pulmonary veins, which, however, gradually ceases, because the blood finds difficulty in entering the pulmonary vessels. When the abdomen is relaxed, the blood again enters the pulmonary vessels in large quantities. Noteworthy in this connection are the experiments of Severini, who found that the flow of blood through the pulmonary vessels is freer and more rapid when the lungs are filled with air rich in carbon dioxid, than with air containing a larger percentage of oxygen. He believes that these gases affect the vascular ganglia in the lesser circulation that control the size of the vessels. According to Morel, electrical and mechanical stimulation of the abdominal organs causes a considerable increase of the blood-pressure in the pulmonary artery (dog). According to v. Basch, increase of blood-pressure in the capillaries of the lungs produces greater rigidity and, therefore, diminished elasticity of the alveolar walls. Pathological. The pressure in the pulmonary area is increased in man in connection with many morbid disturbances of the circulation and always produces accentuation of the second pulmonic sound, which is such an important pathogno- monic sign. It also causes an increase in size and an earlier appearance of the corresponding elevation in the apex-beat curve. But little has been determined with regard to the effect of physiological conditions; temporary suspension of breathing is said always to be followed by an increase in pressure. The influ- ence of the vasomotor nerves on the vessels of the lesser circulation is not so great as that upon those of the greater circulation. Influences that cause a rise or a fall in the blood-pressure in the greater circulation through the agency of the vasomotor or vasodilator nerves have no effect whatever on the pressure in the lesser circulation. Plethora of the pulmonary capillaries is followed by enlargement of the lungs, with more complete distention of the alveoli. The causes may be a diminished flow from the pulmonary veins or disturbances in the left heart. The development of pulmonary edema is discussed on p. 224. MEASUREMENT OF THE VELOCITY OF THE BLOOD-CURRENT. The following instruments are used for determining the velocity of the blood- current in the vessels : i. Alfred Wilhelm Volkmann's hemodromometer measures directly the progress of the blood-column through a glass tube in a blood-vessel. A glass tube shaped like a hairpin, 130 cm. long and 2 or 3 mm. wide and mounted on a scale (Fig. 68, A), is fastened to a metallic basal piece (B) in such a manner that each limb passes to a stopcock perforated all the way through in one direction and halfway through in the other. The basal piece is perforated lengthwise and the two extremities are provided with short cannulae (c c), which are tied into the two ends of the divided blood-vessel. The entire apparatus is next filled with a 0.6 per cent, sodium-chlorid solution. The stop- cocks, which are provided with an arrangement of cogs so that they always turn together, are first placed as shown in Fig. I : the blood then simply flows length- wise through the basal piece; that is, in the same straight direction as the artery. If at a given moment the stopcocks are turned as shown in Fig. 68, II, the blood is forced to flow through the longer channel represented by the glass tube. The blood will be seen pushing the paler column of water before it and the instant should be noted at which it reaches the extremity of the limb of the tube. The length of the tube being known and the time occupied by the blood in passing through it being determined, the velocity for the unit of time and the unit of length of the course is readily obtained. Volkmann found the velocity of the current in the carotid of the dog to be between 205 and 357 mm. ; in the carotid of the horse, 306; in the facial of the horse, 232 ; and in the metatarsal artery, 56 mm. The observation occupies only a few seconds. The tube is narrower than the 172 MEASUREMENT OF THE VELOCITY OF THE BLOOD-CURRENT. blood-vessel; nevertheless the blood is said not to flow more rapidly through it than through the larger, uninjured blood-vessel. The intercalation of the tube offers additional resistance to the blood-current, in consequence of which increased retardation must be produced. The apparatus is evidently imperfect; for the larger respiratory and pulsatory variations of pressure in the arterial system do not produce any perceptible changes in pressure. i FIG. 68. A. A. W. Volkmann's Hemodromometer. B. C. Ludwig's Rheometer. 2. Carl Ludwig's rkeometer measures the velocity of the blood-stream from the amount of blood that passes from the artery into a communicating graduated glass bulb. Two communicating glass bulbs (Fig. 68, B, A and B), of the same capacity and accurately graduated, are attached by their lower extremities to metallic discs e 6j by means of tubes c and d. Each disc can be turned about the axis x y in such a way that after it has been turned the tube c communicates with f and the tube d with g; f and g are, in addition, provided with horizontal cannulae h and k, which are tied into the extremities of the divided artery. When the instrument MEASUREMENT OF THE VELOCITY OF THE BLOOD-CURRENT. is in the position shown in the figure, h is tied in the central, and k in the peripheral extremity of the vessel (for example, the carotid). The bulb A is filled with oil and the bulb B with defibrinated blood. At a given moment the blood-current is permitted to enter through h ; the oil is displaced by the blood and passes over into B, while the defibrinated blood flows out from B through k into the peripheral portion of the vessel. As soon as the oil reaches m, the time is again noted, and the entire apparatus A B is turned about the axis x y, so that B occupies the place of A. The phenomenon is thus repeated, and the observation may often be con- tinued for some time. By observing the time required by the inpouring blood to fill one of the bulbs the quantity for each unit of time (second) can be cal- culated. 3. Carl Vierordt's hemotachometer measures the velocity of the blood-cur- rent by means of a device modeled after Eitelwein's velocity- quadrant, which is constructed on the principle that a pendulum suspended in a moving fluid is deflected by the current in proportion to the velocity. The apparatus consists of a small metallic box (Fig. 69, I. A) with parallel glass sides and provided at the narrow extremities with two cannulae (e, a) for the . iG. 69. Vierordt's Hemotachometer: II, Chauveau's and Lortet's dromograph; III, the dromographic curve according to Chauveau. entrance and exit of the blood. Within the box, opposite the entering blood- current, hangs a small pendulum (p) , the oscillations of which are read off on a curvilinear scale and which increase with the velocity of the current. Before making an observation, water is allowed to flow through the instrument for the purpose of determining the velocity of the fluid that corresponds to each degree of deviation of the pendulum. 4. Chauveau's and Lortet's dromograph is constructed on the same principle, and is in addition provided with a recording contrivance. A sufficiently wide tube (Fig. 69, II, A B), provided with a lateral tube C, which can be connected with a manometer, is introduced into the divided artery (carotid of the horse) . At a there is a small linear opening closed with a rubber plate through which a light pendulum a b projects into the tube. The pendulum is prolonged upward as a thin indicator (b), which makes excursions proportional to the velocity of the current, and which can be read off on the scale S S. G repre- sents a handle for fixing the instrument. The apparatus is first tested with water to determine the excursions corresponding to the various velocities. As the indicating pendulum is exceedingly light it records the slightest changes in velocity. 174 MEASUREMENT OF THE VELOCITY OF THE BLOOD-CURRENT. i. The velocity-curve (Fig. 69, III) is recorded by permitting smoked paper to pass slowly before the tip of the indicator in the direction of its long axis. The apparatus is of value because it registers the characteristic variations in the veloc- ity of the blood-current that accompany each beat of the pulse. The dromographic curve resembles a pulse-curve, and, like the latter, it possesses a primary (P), as well as a secondary, recoil-elevation (R) . 5. Cybulski s photoheniotachometer is constructed on the principle of Pitot's tube. When fluid flows through a tube d e (Fig. 70, //) in the direction indicated by the arrows, the column of fluid stands at a higher level in the manometer p than in the manometer m. While m y indicates only the lateral pressure, p x indicates the lateral pressure and in addition the velocity-height of the fluid. The velocity of the current in the tube may then be de- termined from the difference in the two levels. Fluid may be per- mitted empirically to pass through the tube II d e with varying ve- locity and the difference in level between the two tubes p m that corresponds to the different de- grees of velocity at the current be determined. The form of Pitot's tube em- ployed by Cybulski is somewhat different, being bent at a right angle (/, c p}. The extremity c is tied into the central, and the ex- tremity p into the peripheral, por- tion of the divided artery. When the blood is allowed to flow freely, the fluid rises to a higher level in the manometer a, which lies in the direction of the current, than in b. In order to avoid excessive length in the manometers a and b and thus to render the apparatus practically useful, Cybulski con- nects the manometers a and b by a tube shaped like a hairpin, which is filled with air and can be closed by means of a stopcock (i) applied above the bend. The fluid is allowed to rise to the points i and 2. If the stopcock (i) is then closed, the tubes represent an air-manometer ,u f ba CybU ' Ski S j" ^ich the difference between the levels i and 2 is sharply defined. As the surfaces of the columns of fluid i and 2 continually alter their position with respiration and pulse-beat, that is, as the manometers record the respiratory and pulsatory variations in the velocity of the fluid passing through the tube c p, the fluctuations of the two levels may be advantageously photographed with a camera provided with a rapidly moving background, K. Fig. C is a reproduction of the curves obtained from the carotid artery of the dog. During the time represented by the interval between i l and i the velocity was 238 mm.; in the phase between 2jand 2, 225 mm.; and, finally, between 3 t and 3,177 mm. The velocity is greatest at the end of inspiration and at the beginning of expiration. Asphyxia at first increases the velocity. It is increased by paraly- sis of the sympathetic and becomes smaller when the nerve is stimulated. Divi- sion of the vagus increases the velocity, while stimulation of the nerve naturally diminishes it. FI - 7 VELOCITY OF THE CURRENT. 175 THE VELOCITY OF THE CURRENT IN THE ARTERIES, CAPILLARIES, AND VEINS. In analyzing the results of observation on the velocity of the blood it must be constantly borne in mind that the sectional area of the arterial system beginning with the trunk of the aorta increases pro- gressively by subdivision of the branches, so that in the capillary system the sectional area of the blood-channel is increased yoo-fold and more. From this point, owing to the reunion of the venous trunks, the sectional area again diminishes, but it is still greater than at the beginning of the arterial system. Exceptions are found in the common iliac arteries, which, taken together, are narrower than the trunk of the aorta. The cross-section of the four pulmo- nary veins, taken together, is also somewhat smaller than that of the pulmonary artery. An equal quantity of blood must pass through each successive trans- verse section of both the greater and the lesser circulation. Therefore, the same quantity of blood must flow through the aorta and the pul- monary artery in spite of the great difference between the pressure in the two vessels. The velocity of the blood-current in the individual transverse sections of the blood-channel must, thus, be inversely proportional to the lumen or their sectional area. Hence, there is a marked progressive diminution in the velocity from the root of the aorta and pulmonary artery to the capillaries; so that in mammals it is only 0.8 mm. a second (in the frog 0.53 mm.), and in man from 0.6 to 0.9 mm. According to A. W. Volkmann the velocity of the blood in mammals is 500 times less in the capillaries than in the aorta. Therefore, the total cross-section of all the capil- laries must be 500 times greater than that of the aorta. In the small afferent arteries Bonders found that the velocity was still 10 times greater than in the capillary vessels. In the venous trunks the velocity again becomes accelerated, being, in the large trunks, from 0.5 to 0.75 times less than in the correspond- ing arteries. The velocity of the blood-current does not depend on the height of the mean blood-pressure, and it may accordingly remain the same both in anemic and in plethoric vessels. On the other hand, the velocity in a given section of the circulation is determined by the difference between the pressure in the cross-section at the beginning and that at the end of the section. It will, therefore, depend on, i, the vis a tergo (heart's action) and, 2, the amount of resistance at the periphery (dilatation or narrowing of the smaller vessels) to the arterial current. In accordance with the slight difference in pressure in the arterial and venous systems in the fetus the velocity here is low. In the arteries every pulse-beat causes an acceleration in the move- ment of the current (as well as an increase in the blood-pressure) corre- sponding to the form of the pulse-curve. In large vascular trunks C. Vierordt found the pulsatory increase of velocity to be from i to ^ of the velocity during the diastole. These pulsatory variations in the veloc- ity of the current have been recorded by Chauveau by means of his 176 ESTIMATION OF THE CAPACITY OF THE VENTRICLES. dromograph. Fig. 69 III shows the velocity-curve taken from the carotid of a horse and which corresponds with the pulse-curve in indicating the primary elevation (P), as well as the dicrotic elevation (R). Examination of an extremity with the plethysmograph also discloses this velocity-pulsation or volume-pulsation. In the small arteries an additional pulsatory acceleration is observed, which occurs more rapidly in the first phase than in the later ones. The small trunks themselves are not visibly distended under such circumstances. As the capillary region is approached this phenomenon, ..like the pulse- movement in general, disappears. In the arteries the velocity must be retarded by each inspiration and increased by each expiration; but the differences here are exceed- ingly small. If what has been said in the foregoing concerning the influence of the respira- tory pressure on the dilatation and contraction of the heart, and, therefore, on the movement of the blood, be compared, it will be evident that the respiration must also have an accelerating influence on the blood-current. Likewise, artificial respiration has the same effect: When artificial respiration is suspended in a curarized animal, the blood-current at once becomes slower. If, however, the suspension is continued for some time, the current becomes again accelerated in consequence of the resulting dyspneic irritation of the vasomotor center. In the veins many derangements in the uniform flow of the blood occur : i . Regular fluctuations caused by respiration and the movements of the heart at the points where the large trunks empty into the heart. 2. Irregular effects due to pressure, friction in the direction of the current or in the opposite direction, changes in the position either of the body or of the limbs, a pump-like action in the iliac vein due to walking, etc. During extension and outward rotation of the thigh the crural vein relaxes and collapses in the iliac fossa and the internal pressure becomes negative; while when the thigh is flexed and elevated, the vein becomes filled to distention and the pressure rises. By means of this pump-like action the blood (with the aid of the valves) is forced upward. A somewhat similar phenomenon takes place during walking. ESTIMATION OF THE CAPACITY OF THE VENTRICLES FROM THE CURRENT- VELOCITY BY THE METHOD OF CARL VIERORDT. There may be considered at this point Vierordt's attempt to estimate the capacity of the ventricles, which is based on the velocity of the blood-current in the innominate artery, in the aorta immediately before the origin of this trunk ^ as well as in the coronary arteries; although his ^premises are exceedingly uncertain. (a) The velocity of the current in the right carotid is 26.1 cm. in a second; the cross-section of the vessel is 0.63 square cm.; hence, the quantity of blood that flows through it is 26.1 X 0.63 = 16.4 cu. cm. (i). (&) The velocity of the current in the right subclavian artery is 26.1 cm. a second; the cross-section of the vessel is 0.99 square cm.; hence, the quantity of blood that flows through it is 26.1 cm. X -99 = 2 5-8 cu - cm - ( 2 ) By adding i and 2 the quantity of blood that flows through the innominate artery is obtained: 16.4 + 25.8 = 42.2 cu. cm. The cross-section of this artery is 1.44 square cm. (c) The cross-section of the aorta immediately before the origin of the in- nominate artery is 4.39 square cm.; the velocity of the current in the aorta is estimated to be about one-fourth greater than in the innominate, that is, 36.6 cm.; hence, the quantity of blood that flows through it is 161 cu. cm. (3). (d) The quantity of blood that flows through the two coronary arteries may be assumed to be 4 cu. cm. (4). Hence, the entire quantity of blood that flows THE DURATION OF THE CIRCULATION. 177 through the cross-section of these vessels is (1 + 2 + 3 + 4) 207 2 cu cm As the left ventricle must furnish this quantity of blood in a second, and as, in addition one and one-fifth of the systole corresponds to i second, the quantity of blood thrown into the aorta at each systole must be 172 cu. cm., or 180 grams of blood which is the capacity of the left ventricle. THE DURATION OF THE CIRCULATION. The question as to the time required by the blood to make the entire circuit of the circulation was first investigated by Edward Hering, in 1829, in horses by injecting a solution of potassium ferrocyanid into the external jugular vein and noting the time when this substance first appeared in blood withdrawn from the corresponding vein on the opposite side of the neck. Carl Vierordt, in 1858, per- fected the technic of these experiments by having a number of cups on a rotating disc pass at uniform intervals beneath the opened vein on the opposite side of the body. The first appearance of the 2 per cent, solution of potassium ferro- cyanid is recognized by adding ferric chlorid to the serum separated from the specimen of blood and the development of a Prussian-blue reaction. The duration of the circulation was found to be as follows: In the horse 31.5 sec. In the goose 10.89 se c. dog 16.7 ' duck 10.64 " rabbit 7.79 " buzzard 6.73 " hedge-hog 7.61" " cock e 17 " cat 6.69 " A comparison of these values with the normal pulse-frequency of the same animals yields the following laws: 1. The average duration of the circulation corresponds with 27 con- tractions of the heart. Applying this figure to man, the duration of the circulation is 22.5 seconds, with 72 pulse-beats in the minute. If, therefore, the entire quantity of blood passes through the heart in 22.5 seconds, ^ of the entire quantity must pass through in i second. This quantity is designated the second-volume of the circulation. The latter multiplied by 60 gives the minute-volume, and as there are 72 heart-beats in the minute, the minute- volume divided by 72 represents the amount of blood propelled at each beat of the heart, that is, the pulse-volume of the ventricles. The last calculations, how- ever, are exposed to serious sources of error. 2. In general the mean duration of the circulation in two species of warm-blooded animals is inversely proportional to the pulse-fre- quency. Of the influences that affect the duration of the circulation there may be mentioned: 1. A greater length of the vascular channel (for example, from the metatarsal vein of one foot to that of the other) requires a longer time than a shorter channel. This excess in time may be equivalent to about 10 per cent, of the diameter of the circulation. 2. Young animals, with shorter vascular channels and greater pulse-frequency, have a shorter circulation-time than old animals. 3. Rapid and effective contractions of the heart, as during muscular exertion, shorten the time. On the other hand, rapid but ineffective contractions (as after division of both vagi) , and slow but correspondingly larger contractions (as with slight irritation of the vagus) , appear to have scarcely any effect. Carl Vierordt has, further, attempted to determine the quantity of blood in man from his investigations in the following manner: In all warm-blooded animals the circulation is completed by 27 contractions of the heart; hence, the entire quantity of blood must be equal to 27 times the ventricular capacity; therefore, in man, 27 times 187.5 grams, or 5062.5 grams. This quantity of blood, estimated as T V of the body-weight, would correspond to a body-weight of 65.8 kilos. In 1879 Landois called attention to the fact that potassium ferrocyanid, being a neutral potassium-salt, is a heart-poison, which, in small doses, accelerates, and in large doses paralyzes, the heart. These experiments, in the course of which 178 THE WORK OF THE HEART. numerous animals die, thus, of themselves, cause disturbances in the circulation. It was therefore suggested that the experiments be repeated with a substance that truly is chemically indifferent, or perhaps with the microscopic demonstra- tion of particles introduced into the circulation (such as heterogeneous blood- corpuscles, milk-globules or pigment-granules) . Accordingly, L. Hermann, in 1884, selected the innocuous sodium ferrocyanid. Wolff, thus found the duration of the circulation in the rabbit to be 5^5 seconds, and it is therefore probable that in other animals also the time is shorter than that given by Vierordt. Landois injected mammalian blood-corpuscles into the lateral abdominal vein of frogs and searched for them microscopically on the opposite side. In this way he found the time from 7 to 1 1 seconds, v. Kries has recently expressed some doubt as to the general applicability of the method even from a physical standpoint. The substances first encountered .are carried along only in the axial stream of the blood-vessels, and no conclusion, therefore, can be drawn from their appearance as to the circulation of the entire mass of the blood. Stewart employed a different method. If the electrical resistance offered by an unopened artery is first determined with a galvanometer, and at a given moment some saline solution is injected into the circulation, the galvanic resistance will be diminished when the saline blood passes through the section in communication with the galvanometer. The instant when this takes place is also noted. In this way Stewart found for the lesser circulation about one-fifth of the entire duration of the circulation ( = 10.4 seconds, in the rabbit and in the dog). The duration of the circulation in the kidney was 8 seconds, in the liver 3.8 seconds. A venous state of the blood increases the duration of the circulation. Pathological. In the presence of fever the duration of the circulation appears to be increased. THE WORK OF THE HEART. Following the method of Johann Alfons Borelli and Daniel Passavant, Julius Robert v. Mayer estimated the work of the heart according to physical principles. The work performed by a motor is expressed in kilogrammeters, that is, the num- ber of kilos that the motor is capable of raising to the height of i meter in the unit of time. Robert v. Mayer calculated that the left ventricle propels with each systole 0.188 kilo of blood, and, in order to raise it into the aorta, has to overcome the pressure existing in that vessel, corresponding to a column of blood 3.21 meters in length. The work of the ventricle at each systole is, therefore, equivalent to 0.188 X 3-21 = 0.604 kilogrammeter. Allowing 75 systoles for each minute, the work of the left ventricle in 24 hours is equal to 0.604 X 75 X 60 X 24 = 65,230 kilogrammeters. The work of the right ventricle is only about of that of the left, or, in other words, about 21,740 kilogrammeters. The work of the two ventricles taken together is, therefore, 86,970 kilogrammeters. The work per- formed by a laborer during 8 working-hours equals 300,000 kilogrammeters, thus not quite four times as much as that of the heart. As all of the kinetic energy of the heart is converted by the resistance encountered within the circula- tion into heat, the work of the heart must result in supplying the body with heat: 425.5 grammeters correspond to i unit of heat, that is, the same force that is capable of raising 425.5 grams to a height of i meter is also capable of raising the temperature of i cu. cm. of water i C. The body, therefore, acquires by the conversion of the kinetic energy of the heart about 204,000 units of heat. As i gram of coal yields 8080 units of heat when consumed, the working heart accomplishes as much for the body as if more than 25 grams of coal were burned in it for the production of heat. The values given would be much smaller if the capacity of the ventricles were assumed to be smaller; for example, 60 cubic centi- meters; on that basis the work of the heart would be equivalent only to 20,000 kilogrammeters, or -^ of the entire muscular work of the body. THE MOVEMENT OF THE BLOOD IN THE SMALLEST VESSELS. In the study of the movement of the blood in the smallest vessels microscopic observation of transparent portions of living animals is the THE MOVEMENT OF THE BLOOD IN THE SMALLEST VESSELS. 179 most important method, and it has been repeatedly employed by various investigators since the time of Malpighi, who was the first to observe the circulation of the blood in the pulmonary vessels of the frog. Method. Suitable objects for study with transmitted light are the tails of tadpoles and young fishes; the web, the tongue, as well as the mesentery stretched and secured by means of pins on a strip of wax pasted to the object- carrier, or the lung of a curarized frog; in mammals the wing of the bat and the nictitating membrane, drawn out from the orbit and spread out by means of threads over a vertical glass slide ; and much less advantageously the mesentery. The following objects can be examined with a low power by reflected light: the blood-vessels of the frog's liver, of the pia mater in the rabbit, of the frog's skin, and of the mucous membrane on the inner aspect of the lip in human beings, as well as of the palpebral and bulbar conjunctivas. With respect to the form and arrangement of the capillaries in the various tissues, the following points are worthy of note: 1. The diameter of the smallest vessels, which permits the passage of the blood-corpuscles only in single file, may, however, vary from 2 to 5 //, and in the larger vessels naturally permits the passage of several corpuscles abreast. 2. The Length is, on the average, about 0.5 millimeter; beyond this limit the vessels either originate by the division of small arteries, or unite to form veins. 3. The number of capillaries is extremely variable, being largest in tissues in which metabolism is most active, as the lungs, the liver, and the muscles; and smaller in others, like the sclera and the nerve-trunks. 4. The presence of numerous anastomoses is particularly striking, with the formation of plexuses, the shape of which depends principally on the form and structure of the basal tissue. Thus, the capillaries are arranged simply in loops in the papillae of the skin; as polygonal, retiform meshworks in the serous mem- branes and on the surface of many glandular acini; as longitudinal tubes running close together between the muscles and the nerve-fibers and between the straight uriniferous tubules; in a radiating manner, converging to a central point in the liver; and in the form of arcade-like loops at the free border of the iris and at the corneo-scleral junction. With regard to the transition of the smallest arteries into the capillaries, a distinction should be made as to whether the minute arterial twigs are end- arteries that is, such as do not anastomose with other arterial twigs of the same order, but break up directly into capillaries, and communicate with neighboring arterial twigs only by means of capillaries; or whether before breaking up into capillaries the neighboring arteries communicate by liberal anastomoses, large enough to be called arterial. The presence or absence of arterial anastomoses is important with respect to the nutrition of the region supplied by the vessels. In observing the blood-current itself it will be seen at once that the red blood-cells progress only along the center of the vessel in the axial stream, while the parietal, transparent layer of plasma remains entirely free from them. The latter, designated Poiseuille's space, is recognizable especially in the smallest arteries and veins, in which the axial stream occupies three-fifths, and the light layer of plasma one-fifth, of the entire width of the vessel. It is less distinct in the capillaries. Accord- ing to Rud. Wagner, Poiseuille's space is wholly absent in the smallest vessels of the lungs and the gills. The red blood-cells pass through the smallest capillaries in single file. In larger vessels they move close to- gether, frequently turning and twisting in their course. On the whole, the rate of 'progress in the larger vessels is uniform; occasionally, how- ever, as when there is a sharp bend in a vessel, the movement is at times somewhat retarded, at times again accelerated. Wherever the stream divides, a blood-cell occasionally remains attached to the projecting ridge at the point of division, bending at its edges on each side into the bifurcation of the capillary, and appearing somewhat thinned at the center. Often it may adhere in this way for a long while, until, the cur- l8o MIGRATION OF THE BLOOD-CORPUSCLES FROM THE VESSELS. rent becoming accidentally stronger on one side, it is set free, whereupon it rapidly regains its former shape by virtue of its inherent elasticity. When two vessels join to form one, the elasticity of the red blood-cells is again put to proof. Cells at such points are not infrequently heaped up and pushed together in one direction or another. Occasionally, an accumulation of this kind causes a temporary stagnation first in one of the branches and then in the other; the obstruction is then removed, and for some time both capillaries continue to pour their contents into the collecting tube, during which process the corpuscles are shaken up, like dice in a box. The movement of the white blood-cells is entirely different. They roll along the walls of the blood-vessels, their peripheral zone bathed by the plasma of Poiseuille's space and their inner spherical surface pro- jecting into the procession of red blood- cells. The explanation of this peculiar property on the part of the leukocytes of keeping close to the vessel-wall has been furnished by Schklarewski, who dem- onstrated by certain physical experiments that in capillary tubes in general (as, for example, glass tubes), containing artificial mixtures of different kinds of granular bodies, those possessing the lowest specific gravity are forced to the wall when a current is set up in the tube, while those having a higher specific gravity move along in the middle of the stream. Thus, when once forced against the wall, the leukocytes must keep on rolling, partly on account of the viscosity of their surface, which causes them to adhere readily to the vessel- wall, and partly because the surface directed toward the axis of the vessel, where the current is swiftest, receives the most effective impulse, often by the direct impact of red corpuscles driven against it. The rolling movement is not rarely intermittent, probably because different parts of the leukocytes adhere with equal tenacity to the vessel- wall. The viscosity of the leukocytes is also in part responsible for their slower movement, which is from ten to twelve times slower than that of the red blood-cells; this is, however, in part also due to the fact that, owing to their parietal position, the larger portion of the body of the leukocyte projects into the peripheral layers of the cylindrical stream, where the current is least rapid. It is an interesting observation that in the vessels first formed in the incu- bated egg, as well as in young tadpoles, the movement of the blood from the heart is intermittent. The velocity of the stream is influenced also by the diameter of the vessels at a given point. The latter is subject to periodical variations, not only in vessels provided with muscular tissue, but also in the capillaries in the latter in conse- quence of spontaneous contraction of the protoplasmic cells that form their walls. In the pulmonary capillaries the blood-stream is more rapid than in those of the greater circulation, whence it may be concluded that the total sectional area of the pulmonary capillaries must be smaller than that of all of the capillaries of the body (of the greater circulation) . THE MIGRATION OF THE BLOOD-CORPUSCLES FROM THE VESSELS ; STASIS ; DIAPEDESIS. If the circulation be observed in the mesenteric vessels it is not rarely possible, especially if, after the application of a mild irritant to this vascular tissue (the contact of the air alone is sufficient), an inflammatory process begins to develop, to see the migration of leukocytes in varying numbers through the vessel-wall. Instead of rolling along in a jerky manner in the plasmatic zone, the cells gradually move more and more slowly, accumulate in increasing numbers and adhere firmly MIGRATION OF THE BLOOD-CORPUSCLES FROM THE VESSELS. l8l to the wall; soon they begin to penetrate into the wall and ultimately they make their way completely through it and wander for some distance further into the peri- vascular tissue. It is still a matter of doubt whether the corpuscles force their way through interendothelial stomata, supposed to be present, and then enter the lymphatic vascular system, or whether they simply pass through the cement- substance between the endothelial cells. Several successive steps can be distin- guished in this process of migration, which is known as diapedesis ; (a) adhesion of the leukocytes to the inner surface of the vessel (after gradual retardation in their progress along the wall up to that point) ; (b) extension of processes into and through the vessel-wall; (c) withdrawal of the cell-body, which appears con- stricted at the instant of its passage through the wall of the compression; (d) com- plete passage through the vessel-wall and the further progress of the leukocyte by virtue of its ameboid movement. Hering observed that, even under normal conditions, the leukocytes in larger vessels, which are surrounded by lymph-spaces, pass into the lymph-spaces. This observation explains why cells may be found even in such lymph as has not yet passed through any gland. The cause of the migration from the vessels resides, in part, in the independent power of movement on the part of the leukocytes; in part it is a physical phenomenon, namely filtration of the colloid mass of the cell- bodies through the force of the blood-pressure, and in the latter connection, there- fore, essentially dependent upon the intravascular pressure and the velocity of the blood-current. Hering regards the migration of leukocytes and even of a few red blood-cells from the small vessels into the lymphatics as a normal process, which he was able to observe in the mesentery of the frog. The red blood-cells escape from the vessel in the presence of obstruction to the venous flow, which causes, first, escape of blood-plasma through the vessel-wall, and with the plasma the erythrocytes are also forced through, undergoing a marked change of shape on account of the torsion to which they are subjected at the moment when they pass through the vessel-wall, but regaining their shape again after the passage is completed. The migration of blood-cells had already been described in 1824 by Dutrochet and in 1846 by Waller; the phenomenon was next more carefully studied by Cohnheim. According to the latter, the migration is a sign of inflammation, and the leukocytes, which accumulate in considerable numbers in the tissue, are to be regarded as true pus-cor- puscles, which may later multiply by division. It should, however, be distinctly stated that, in addition, the connective-tissue cells are also capable, by multiplication, of produc- ing pus-corpuscles, which differ by their greater size from the migrated leukocytes found in pus. When a vascular part is sub- jected to severe irritation, hyper- emic reddening and swelling of the part are at once observed. It has been shown by microscopic examina- tion of transparent parts that both the capillaries and the smaller ves- sels become dilated and engorged with blood-cells; sometimes dilata- tion is preceded by a temporary contraction of brief duration. At the same time, a change in the ve- locity of the blood-stream is observed in the vessels. Rarely, and, as a rule, only for a short time, the blood-stream is accelerated; but generally it is retarded. If the irritation be continued, the retardation soon becomes so great that the current only advances intermittently, and a to-and-fro movement of the blood- column is observed, a sign that obstruction has already taken place in peripherally situated vascular areas. Finally, the current in the distended vessels comes to a complete standstill (stasis) . Bonders points out the greater number of leukocytes in stagnating blood, and believes correctly that this accumulation of leukocytes is a greater obstacle to their progress, as compared with the erythrocytes. FIG. 71. Small Mesenteric Vessel from a Frog Show- ing the Migration of Leukocytes: w w, vessel-wall; a a, Poiseuille's space; r r, red blood-corpuscles; 1 1, leukocytes moving along the wall, at c c in various stages of migration; f f, migrated cells. While 182 THE MOVEMENT OF THE BLOOD IN THE VEINS. these processes are going on, the migration of the leukocytes and rarely also of the red cells takes place. Under favorable conditions the stasis may be relieved, generally with a reversal in the order of the phenomena that have attended its development. The escape of blood-corpuscles through the intact wall of the vessel is designated diapedesis. The swelling of inflamed parts is due in part to the dilatation of the vessels, but chiefly to the escape of plasma into the tissues. THE MOVEMENT OF THE BLOOD IN THE VEINS. In the smallest veins, which are formed by the union of capillaries, the velocity of the blood-current is greater than in the capillaries, but slower than in the smallest arteries. At the same time, the current is everywhere uniform, and according to hydrodynamic laws the venous current would continue with absolute regularity to the heart, if it were not subject to other disturbances. Such disturbances, however, are operative in various directions. Among special peculiarities of the veins to which interference with the uniformity of the current is attrib- utable the following may be mentioned: i. The relative relaxation, the great distensibility and compress- ibility of even the larger trunks; 2, the incomplete distention, which does not increase to any considerable degree the elastic tension of the walls; 3, the numerous and at the same time free anastomoses among neighboring trunks, both in the same tissue-plane and from above down- ward. By this means it is possible for the blood, when the venous area is partly compressed, to escape through numerous readily distensible channels, and thus the occurrence of actual stasis is prevented; 4, the presence of numerous valves, which permit the blood-current to move only in a centripetal direction. These are wanting in the smallest veins, and they are most numerous in the medium-sized veins. The valves are of great hydrostatic significance, inasmuch as they divide long columns of blood, as, for example, in the crural vein when the body is in the erect position, into sections, thus preventing the entire column from exerting its hydrostatic pressure down to the lowest portions of the vein. As soon as pressure is exerted on a vein, the nearest valves below the point of pressure close and those next above open, thus leaving a free passage for the blood to the heart. The pressure on the veins may be of varied character: in the first place from without, by contact with various objects. Further, thickened and contracted muscles may com- press the veins, especially in the movements of the extremities. That the blood escapes in a stronger stream from an opened vein when the muscles are moved at the same time can be seen whenever venesection is practised. If the muscles are permanently contracted, the venous blood, escaping from the muscles, collects in the parts that are not moved, especially in the cutaneous veins. The pulsatory pressure in the arteries accompanying the veins also tends to accelerate the venous current. Direct observations have been made as to the velocity of the venous blood- current with the hemodromometer and the rheometer. Thus, Volkmann found a velocity of 225 mm. in a second for the jugular vein; but in view of the low pressure that prevails in the venous system, the employment of instruments for measuring the velocity is necessarily attended with marked deviations from the normal. Reil observed that the quantity of blood escaping from an opening in an artery was two and a half times as great as the quantity of blood escaping from a similar opening in a vein. SOUNDS AND MURMURS IN THE ARTERIES. 183 As the smaller venous branches unite to form larger ones, the lumen gradually diminishes toward the venae cavae : hence the velocity of the current must increase in the same proportion. The velocity in the venae cavae may be half as great as that in the aorta. Borelli estimated the capacity of the venous system as four times as large as that of the arteries. According to A. v. Haller the proportion is as 9 14. As the pulmonary veins are narrower than the pulmonary arteries, the blood moves more rapidly through the former than through the latter. SOUNDS AND MURMURS IN THE ARTERIES. The acoustic phenomena observed in the arteries must, from a strictly physical standpoint, be designated as murmurs. Nevertheless it is customary in medical nomenclature, following the example of Skoda, to apply the term sound to those acoustic phenomena that are of short duration and sharp definition, like the heart- sounds; while those that are of longer duration and are not distinctly delimited are designated murmurs in the narrower sense. In many cases a sharp distinction between the two is, therefore, impossible. In the carotid, and more rarely in the subclavian, two distinct sounds are heard in approximately four-fifths of all healthy individuals. These sounds cor- respond in duration and pitch to the two sounds of the heart and must be inter- preted as due to propagation of the sound from the heart by means of the blood as far as the carotid, and they are, accordingly, designated transmitted heart- sounds. Sometimes the second sound of the heart alone is heard, as the site of its production is nearer the carotid. The second sound of the pulmonary artery, which is in close contact with the aorta, may also be transmitted to the point mentioned. Sounds and murmurs occur either spontaneously or only after the application of external pressure, by means of which the lumen of the vessel is narrowed. Accordingly a distinction is made between (i) spontaneous sounds and murmurs and (2) pressure-sounds and pressure-murmurs. Arterial murmurs are developed most easily by exerting pressure on a circum- scribed portion of a large artery, for example, the femoral. The pressure must be so regulated that only a small portion of the lumen remains open for the passage of the blood (stenotic murmurs}. As a result, a small stream of blood will pass through the stenotic point with great rapidity and force, and enter the wider por- tion of the artery beyond the site of compression. This so-called pressure-stream throws the fluid-particles into active oscillatory and rotatory movement and thus produces the murmur in the wider, peripheral portion of the vessel. Analo- gous conditions prevail wherever there is a kink, a sharp bend or a tortuosity in the course of the artery. The phenomenon is, therefore, as a rule a pressure- murmur generated within the fluid. With regard to the question as to the origin of these murmurs, Geigel takes the stand that they are due to static transverse vibrations of the vessel-walls. Below the point of compression a thrill is felt in the walls of the large arteries synchronously with the pressure-murmur. In cases of aortic insufficiency, exophthalmic goiter, and circumscribed arteriosclerosis this thrill is much more marked than in normal cases, and it is also appreciable over smaller arteries. A murmur of like character is that at times heard over the subclavian artery synchronously with the pulse and designated subclavian murmur. This is pro- duced by adhesions of the two layers of the pleura at the apices of the lungs, especially in association with tuberculosis and other diseases of the lungs, and in consequence of which the subclavian artery, as a result of torsion and kinking, undergoes local stenosis, which sometimes manifests itself by diminution or absence of the pulse-wave in the radial artery (paradoxical pulse) . Pathological. It is evident that murmurs will develop in the human body likewise: (a) When, owing to morbid conditions, the arterial tube is dilated at some point where the blood-current is forcibly introduced from a normal portion of the artery. Such dilatations (aneurysms) quite generally give rise to murmurs (bruits) . (6) Pressure-murmurs will be generated whenever an organ exerts pres- sure on an artery, as, for example, by the greatly enlarged uterus during preg- nancy, and by a pathological tumor pressing upon a large artery. 184 ACOUSTIC PHENOMENA WITHIN THE VEINS. In all cases in which there is no external pressure, it is found that the pro- duction of spontaneous acoustic phenomena is greatly facilitated if, during the period of arterial diastole, the arterial wall is as relaxed as possible and, therefore, becomes suddenly and greatly distended at the time of the pulse-wave, that is, when the systolic minimum of tension of the arterial wall is rapidly displaced by the diastolic maxirmim of tension. This is particularly the case with aortic in- sufficiency, a condition in which the arteries are often the seat of widespread murmurs. If even during arterial rest the minimum of tension of the arterial wall is relatively high, the acoustic phenomena are faint and may even disappear altogether. The following factors favor the development of arterial murmurs: (i) A suffi- cient degree of delicacy and elasticity of the vessel-walls; (2) a low peripheral resistance, that is, accelerated and unobstructed escape of the blood from the end of the vascular channel; (3) a material difference between the pressure ot the fluid in the stenotic portion and that of the fluid in the peripheral dilatation; (4) large size of the artery. Murmurs may be heard also in normal pulsating arteries, especially when the vessel is the seat of sharp bends or tortuosities. In almost all cases in which arterial murmurs are heard, one or several of the foregoing factors can be demon- strated. It is evident that murmurs of this kind will be most marked when two or three large arteries are found in close apposition. Hence the rather loud murmur generated in the many tortuous and dilated arterial trunks of the gravid uterus (uterine or placental souffle) and the much less distinct funic souffle in the two umbilical arteries. In this category belongs also the so-called cerebral murmur heard in almost one-half of all infants with thin skulls, as well as the murmur heard over the morbidly enlarged spleen, and the thrill in the thyroid gland in cases of exophthalmic goiter. When auscultation is practised over the ulnar artery under the favorable conditions mentioned, especially in lean individuals, every pulse-beat is found to be accompanied by two acoustic phenomena, which coincide with the primary and the dicrotic elevation. In old persons especially, and in individuals with a bigeminate pulse, the two sounds are quite distinct. Friedreich believes the first sound to be produced by the vessel-wall, that is, the sudden tension of the artery distended during diastole. The second murmur naturally is feebler, in correspond- ence with the lesser degree of distention of the artery by the dicrotic elevation. Occasionally a third sound is heard between the other two, which corresponds to the elasticity-oscillations between the apex of the curve and the dicrotic elevation. In the radial artery and in the dorsalis pedis only a single murmur is, as a rule, heard synchronously with the pulse-beat. In cases of aortic insufficiency characteristic acoustic phenomena are present in the femoral artery. When the vessel is compressed, there is heard a double blowing (murmur) , the first element of which is due to the fact that a large mass of blood is driven to the periphery synchronously with the pulse, and the second to the fact that during the contraction of the artery a large quantity of blood flows back into the ventricle. On the other hand, if the artery is not compressed, two feebler sounds are heard, which are due to the fact that the auricle and the ven- tricle send a wave of blood into the arterial system in rapid succession (Fig. 55, III) . Gerhardt similarly heard, in cases of insufficiency of the pulmonary valves, two dull sounds over every portion of the pulmonary surface. In other cases (when there is also tricuspid insufficiency) the second sound is produced by the sudden snapping closure of the valves in the femoral veins, caused by the rebound of the venous blood. Also, when the arteries are rigid (atheroma) a double sound is sometimes heard synchronously with the pulse- wave. This sound is attributed to the anacrotism of the pulse observed under such conditions. ACOUSTIC PHENOMENA WITHIN THE VEINS. The Venous Hum. Above the clavicle, in the fossa between the origin of the two heads of the sternocleidomastoid muscle, most commonly on the right side, there is heard in many individuals (40 per cent.) a sound that may be continuous, or synchronous with the diastole of the heart, or even with inspiration, and of a roaring or buzzing, sometimes hissing or singing, character. This sound is generated within the bulb of the common jugular vein and is called a venous hum. If present even when no pressure is exerted with the stethoscope, it is a pathological symptom. The phenomenon may be heard in almost any subject if pressure be THE VENOUS PULSE. THE PHLEBOGRAM. 185 exerted and the head is at the same time turned to the opposite side and slightly upward. The pathological venous hum occurs chiefly in young anemic individuals in whom also a thrill is felt over the vessel; it is present also in cases of goiter, at times in youthful individuals, but it becomes less common with advancing age The cause of the venous hum resides in the whirling entrance of the blood from the relatively narrow portion of the common jugular vein into the dilated bulb situated below. It appears to be generated chiefly when the walls of the thinner portion of the vein are in fairlv close apposition, so that the blood-stream is obliged to force its way through. This explains the fact that the occurrence of the phenomenon is favored by pressure and by turning the head to the side and slightly upward. The intensity of the sound depends upon the velocity of the blood as it passes through the narrow portion of the vein, and for this reason the act of inspiration and the diastole of the heart, both factors accelerating the venous flow, intensify the venous hum. The same is true with regard to the favorable influence of the erect posture. In rare cases a sound similar to the venous hum is heard in the subclavian, axillary, thyroid (in cases of goiter), facial and innominate veins, the superior vena cava, the crural vein, and the inferior vena cava at the blunt margin of the liver. Regurgitant Murmurs. The expiratory murmur heard at times in the crural vein after sudden efforts at bearing-down is produced by a centrifugal current of blood passing through the vein at the bend of the knee, the valves being incompetent or entirely absent. When the valves in the bulb of the jugular vein are incompetent, a regurgitant murmur may be produced either during expiration (expiratory jugular- valve murmur) or during the systole of the heart (systolic jugular- valve murmur) . In the presence of insufficiency of the tricuspid valve a systolic murmur has been heard in the crural vein when its valves were incompetent. Valvular Sounds in the Veins. Forced expiration may give rise to valvular sounds in the crural vein, as the valves close with a snap under the pressure of the blood forced back. In the presence of insufficiency of the tricuspid valve a large quantity of blood is thrown back into the venae cavae at each ventricular systole. Under such circumstances also the venous valves may close suddenly with the production of a sound. The phenomenon occurs both in the bulb of the jugular vein and in the crural vein at the bend of the knee, but only when the respective valves are competent. THE VENOUS PULSE. THE PHLEBOGRAM. Method. If the movements of a vein are recorded by means of a lightly weighted sphygmograph a heavy load would compress the vein or at least obliterate the delicate details of the curve a characteristic form will be observed in a successful venous pulse-curve or phlebogram (Fig. 72). In the proper interpretation of the details of the phlebogram it is especially important to determine its chronological relations to the phases of the heart's action; hence, it is advisable to record a cardiogram and a phlebogram simulta- neously (on a recording surface attached to a vibrating tuning-fork) . The begin- ning of the carotid pulse coincides approximately with the apex of the cardiogram, that is to say, with the descending limb of the phlebogram. The venous pulse within the common jugular vein is a normal phenomenon. A pulsating movement synchronous with the movements of the heart is frequently observed in the course of this vein. (Compare Fig. 34.) The movement may extend only to the lower portion of the vein, the so-called bulb, or higher up to the trunk of the vein itself. When the valves of the common jugular vein above the bulb are incompetent, a condition that is not at all rare, even in healthy per- sons, the phenomenon is particularly marked. The undulating movement ad- vances from below upward; as a rule, it is observed only when the subject lies quietly in the horizontal position; it is more common on the right than on the left side, because the course of the right vein is straight and the vessel is nearer the heart than the left vein. The movement is propagated more slowly than the arterial pulse-wave. The venous pulse possesses the peculiarities of the movement of the heart. The tracing exhibits in a marked degree all of the details of tin- a] u-x-bcat curve, especially in connection with the pathological conditions to be discussed presently, and it there- fore closely resembles such a curve, as is shown beyond a doubt by a comparison of the venous pulse-curve (Fig. 72, i) with the apex-beat curve (Fig. 28, A). i86 THE VENOUS PULSE. THE PHLEBOGRAM. If it be considered that the distended jugular vein, in which the blood is subject only to slight pressure, communicates directly with the auricle, it will be readily understood that a contraction of the auricle will be propagated peripherally into the jugular vein as a positive wave. In Fig. 72, 9 and 10 represent the venous pulse from healthy individuals : the section a b corresponds to the auricular contraction. Landois has occasionally seen this composed of two slight elevations, corresponding to the contraction of the auricular appendage and the auricle. As the blood of the right auricle is subsequently thrown into agitation by the sudden tension of the tricuspid valve, the closure of the latter, which is synchronous with the systole of the right ventricle, sends a positive wave into the jugular vein, and this appears in 9 and 10 as the section b c. Finally, the sudden closure of the pulmonary valves may even be propagated through the blood in the ventricle as far as the auricle and still further up in the jugular vein, and be registered by the production of a small positive wave (e) . As the aorta is in immediate contact with the pulmonary artery, a delicate wave may, on sudden closure of the aortic valves (in 9 at d), be generated at this point in a similar manner. During the FIG. 72. Various Forms of Venous Pulse, Chiefly after Friedreich: 1-8, with tricuspid insufficiency; 9 and 10, venous pulse from the jugular vein of a healthy individual. In all of the curves a b indicate contraction of the right auricle; b c, that of the right ventricle; d, closure of the aortic valves; e, closure of the pulmonary valves; e f, diastole of the right auricle. diastole of the auricle and of the ventricle blood flows freely toward the heart, and in consequence the vein collapses and the writing-lever makes a down-stroke. According to Knoll the normal jugular pulse is due partly to the positive wave caused by the contraction of the right auricle and partly to the negative wave caused by the dilatation of the ventricle ; while, the increase in the venous pressure that takes place between these two phases is brought about by interference with the flow of venous blood to the heart during the auricular pause. In the sinuses of the skull the blood likewise exhibits pulsatory movement, because blood flows freely into the heart during diastolic relaxation. Under favorable conditions this pulsatory movement may be propagated as far as the veins of the retina and thus give rise to the retinal venous pulse, which was familiar to the earlier investigators. Pathological. The venous pulse may be much larger and much more pro- nounced in all its characteristic parts in cases of tricuspid insufficiency. A mo- ment's reflection will show that under such circumstances every contraction of the right ventricle must cause regurgitation of a certain quantity of blood into THE VENOUS PULSE. THE PHLEBOGRAM. 187 the veins, by which a marked wave may be produced. As a rule, the common jugular vein pulsates quite strongly in cases of tricuspid insufficiency; but when the valves at the bulb of the jugular vein are still competent, the pulse is not propagated into the vein itself. The jugular pulse is, therefore, not a necessary sign .of tricuspid insufficiency, but only a sign of insufficiency of the valves of the jugular vein. The ventricular systole, however, is always propagated into the inferior vena cava, which is without valves, and there it produces especially the so-called liver-pulse. Each ventricular contraction throws a large quantity of blood as far as the hepatic veins and thus the liver undergoes systolic swelling and distention due to injection. The figures from 2 to 8 represent tracings from the common jugular vein. In all the curves, a b indicates the auricular contraction; the contracting auricle throws a positive wave into the veins. This portion of the curve appears at times as a simple anacrotic basal elevation (3). Not infrequently (as particularly in i, representing a curve from one of the thyroid veins) two or three small notches make their appearance at this point, and these may be compared with the analo- gous elevations in the cardiogram. In accordance with the tension of the vein, as well as with the freedom of the flow of blood from the vein to the heart, and also with the respiratory position of the thorax, the auricular notch may appear in the descending portion of the foregoing curve, as in 5 and 8; at times alternately as in 3 and 8 (see 7) ; at other times, a portion of the auricular wave may be in the descending portion of the foregoing curve, while the remainder is found in the ascending portion of the same curve, as in 6, 2 and 4. When the action of the auricle is exceedingly feeble, the auricular wave may even be entirely abortive as in 7 at f . The ventricular elevation is caused by the large blood-wave thrown back into the vein by the evacuation of the ventricle. The apex of this wave (c) is at times higher, at other times lower, in accordance with the tension in the vein and the pressure of the sphygmograph. It is usually followed by at least one notch (4, 5, 6 e), produced by the sudden closure of the semilunar valves of the pulmonary artery. It is not surprising that the closure of these valves produces an undulatory movement in the ventricle that is propagated through the constantly open tricuspid valve into the auricle and the veins. The adjacent aorta may even produce a small wave next to e by the closure of its valves (as in i and 2 d) . When the valve-closure becomes feebler in consequence of diminished tension in the large arteries, the aortic-valve wave d is the first to disappear (as in 4 and 5) ; later also the elevation due to closure of the pulmonary valves e disappears (as in 3 and 7). After the closure of the valves the curve falls, in correspondence with the diastole of the heart, as far as f. An especially distinct venous pulse may be produced also when the right auricle is greatly overdistended, as in cases of mitral insufficiency or stenosis. In rare instances other veins pulsate in addition to the common jugular, such as the external jugular, some of the facial veins, the anterior jugular vein, the thyroid, the external thoracic, and the veins of the upper and lower extremities. Landois on one occasion saw extensive venous pulsation in a moribund woman without any cardiac lesion, in whom the autopsy revealed an enormous, white, fibrinous clot extending from the right ventricle into the auricle and making closure of the tricuspid valves impossible; even the cutaneous veins on the anterior surface of the thorax could be seen pulsating strongly. It is evident that pulsations similar to those produced in the veins of the greater circulation in cases of tricuspid insufficiency must also be produced in the pulmonary veins in cases of mitral insufficiency. Such pulsations are, however, not directly visible; although it may be possible to demonstrate their presence by observing the cardiopulmonary movement. In rare cases the veins on the backs of the hands and the feet are seen to pulsate, because the arterial pulse is propagated to the veins through the capillaries, or possibly through some direct communication between the arterial branches and the veins. This phenomenon may occur even under normal conditions, espe- ciallv when the peripheral extremities of the arteries are dilated and relaxed, or when the pressure within them becomes high and falls rapidly again, as in cases of aortic insufficiency. Diastolic collapse of the veins of the neck is observed in association with heart- disease at the instant when the tricuspid valve opens. It is due to deficiem traction of the right auricle. In cases in which the interior of an artery c municates directly with the interior of a vein as a result of traumatism or rupture, the arterial pulse is propagated into the venous channels. l88 THE DISTRIBUTION OF THE BLOOD. THE DISTRIBUTION OF THE BLOOD. The metkods employed for determining the quantity of blood contained in individual organs and members must unfortunately as yet be regarded as inade- quate, (i) The quantity of blood contained in the part may be determined after death in frozen cadavers. This method is inaccurate, because after death, par- ticularly through the stimulation of the vasomotor center, the quantity of blood contained in any given part undergoes profound changes in consequence of the fact that different parts of the body die and freeze at different times. (2) A part may be forcibly ligated off from an animal during life, then be at once severed, and the quantity of blood in the tissues be determined while they are still warm. This method is, unfortunately, inapplicable to many internal organs. J. Ranke determined in this way the distribution of the blood in the living rabbit at rest. He found one-fourth of the entire quantity of blood in (a) the resting muscles, (b) the liver, (c) the circulatory organs (heart and large arterial trunks), (d} the remaining organs taken to- gether; of the last the lungs contained between 7 and 9 per cent. The amount of blood is influenced by: (i) The anatomical distribution of the vessels in general, that is, the number o'f vessels in individual parts of the body; (2) especially the size of the vessels, which is dependent upon physiological causes: (a) the blood-pressure within them; (b) the state of irritability of the vasocon- strictor or vasodilator nerves; (c) the condition of the tissues in which the vessels are situated, for example, the intestinal vessels during the absorption of alimentary juices; the muscular vessels during the contraction of the muscles (vessels in in- flamed parts). The most important factor influencing the quantity of blood in an organ is the activity of the latter. In this connection the ancient dictum "ubi irritatio, ibi affluxus" is applicable. Examples are afforded by the salivary glands, the stomach, and the muscles during activity. As, however, under normal conditions of the body, the individual organs in many ways relieve one another, one organ may in the course of a day be found in a condition of greater plethora at one time and another organ at another time. The variations in the dis- tribution of the blood coincide with the alternations in the functional activity of the organs. Thus, while one organ is in a state of increased activity, the remainder often are resting: the process of digestion is attended with muscular lassitude and mental relaxation; severe mus- cular exertion delays digestion; when the skin is reddened and secreting freely, the action of the kidneys is temporarily in abeyance. Some organs (the heart, the respiratory organs, and certain nerve-centers) appear to maintain a constant level of activity and contain the same quantity of blood at all times. While an organ is active, the amount of blood present may increase up to 30 per cent, or even to 47 per cent. The organs of locomotion in young and vigorous individuals are likewise relatively more plethoric than those of older individuals with a feebler muscular system. During mental activity the carotid is dilated, and the dicrotic elevation of the carotid curve is increased, while the radial exhibits reverse conditions, and the pulse is accelerated. In this condition of greater activity the increased amount of blood usually undergoes more rapid renewal at the same time; for example, after muscular exertion the duration of the circulation is diminished. This circumstance may be affected by a great variety of influences that govern the movement of the blood. PLETHYSMOGRAPHY. 189 The development of the heart and the large blood-vessels is responsible for certain differences in the distribution of the blood in children and in adults. From childhood to puberty the heart is relatively small and the vessels are relatively large. After puberty, on the contrary, the heart is large and the arteries are comparatively small. Accordingly, the arterial blood-pressure in the greater cir- culation must be lower in a child than in an adult. The pulmonary artery is relatively large in childhood, the aorta relatively small; after the onset of puberty both arteries are approximately of the same 'size. Hence, it follows that the blood-pressure in the pulmonary vessels of the child must be relatively higher than in the adult. PLETHYSMOGRAPHY. The plethysmograph is an instrument employed to determine and register the amount of blo'od in an extremity and its variations. It is a perfected apparatus, modeled after the " box-sphygmometer" described by Chelius in 1850 (Fig. 41). It consists of a long container (G), designed for the reception of an entire extremity. The opening around the introduced part is made air-tight by means of rubber, and the interior of the vessel is tilled with water. In the lateral wall of the receptacle is a communicating tube, which also is filled with water to a certain level. As each pulse-beat causes an enlargement of the extremity as a result of the increased flow of arterial blood, the water in the tube will indicate the magnitude of this positive variation in the quantity of blood, which will be transmitted to the drum (T), covered with an elastic membrane, and with which is connected a writing lever moving in a horizontal direction. The cylinder G may also be filled with air. v. Kries connects the tube with a gas-burner instead of with the registering drum (T) , so that the variations in the size of the arm are reproduced in the flame, the flickerings of which may be photographed. FIG. 73. Mosso's Plethysmograph: F, communicating flask, by elevation of the level of which the hydrostatic " pressure may be increased; T, the inscribing apparatus. Individual organs (spleen, kidney) may be enclosed in a box-like apparatus in a similar manner for the purpose of observing fluctuations in their size: onco- graph. The fluctuations of the plethysmograph permit recognition of the following phenomena: i. Pulsatory fluctuations in volume. As the venous current in the resting extremity may be regarded as uniform, any rise in the volume-curve must indicate a greater velocity in the movement of the arterial blood-current toward the periph- ery, and the reverse. The curves registered by this apparatus represent volume- pulsations and resemble a dromographic curve" (Fig. 69, III). A rise in the limb of the curve indicates a greater flow of arterial blood, while a fall indicates a diminution in the flow. If the level of the curve remains the same, it is to be inferred that the arterial inflow of blood is equal to the venous outflow. At first sight the plethysmographic tracing (volume-curve, current-pulse) presents a great similarity to" the sphygmographic tracing (pressure-pulse), espe- cially from the fact that" both exhibit the dicrotic elevation. More careful ex- amination, however, reveals several differences: In the plethysmographic tracing (current-pulse) the curve descends to a much lower level after the primary apex. TRANSFUSION OF BLOOD. This marked fall, which is not accompanied by a corresponding fall in the pressure, is attributed by v. Kries to a peripheral reflection, that is, one in which a positive wave is reflected as such. The dicrotic elevation (secondary wave) appears, further, somewhat earlier in the plethysmographic curve (current-pulse) than in the sphygmographic curve; although it also has a centrifugal course, as in the sphyg- mo graphic curve. 2. The respiratory fluctuations, which correspond to the respiratory fluctua- tions in blood-pressure. Active breathing and cessation of breathing produce a diminution in volume. Further, the part has been observed to undergo enlarge- ment in consequence of effects at bearing down and coughing, and reduction in size during sobbing. 3. Certain periodic fluctuations, dependent upon periodic- regulatory movements of the vessels, particularly of the smaller arteries. 4. Vari- ous fluctuations due to accidental causes that bring about alterations in the blood-pressure, such as change of position producing hydrostatic effects; dilatation or contraction of other large vascular areas. 5. Muscular movements in the ex- tremity introduced into the plethysmograph cause a reduction in volume, because the venous pulse is accelerated, and in addition the musculature itself is somewhat reduced in size, in spite of the fact that the intramuscular vessels are dilated. 6. High (from 33 to 36 C.) and low (from 4 to 8 C.) temperature, when applied to the skin of the arm, increase the volume of the member in consequence of paresis of the muscular coat of the blood-vessels caused by the thermic stimuli. 7. Mental exertion diminishes the volume of the extremity; sleep has the same effect. 8. Compression of the afferent artery causes diminution, while constriction of the veins naturally causes an increase in the volume. 9. Irritation of the vaso- motor nerves is followed by a decrease, that of the vasodilators by an increase, in volume. TRANSFUSION OF BLOOD. Transfusion is the physiological introduction of blood into the vascu- lar system of a living being. The first mention of direct exchange of blood between two individuals from vessel to vessel takes us back to the time of Cardanus. After the discovery of the circulation of the blood, Potter in England again called attention to the prac- ticability of transfusion. Numerous experiments were made on animals. Attempts were made by the introduction of fresh blood particularly to resuscitate animals that had bled to death. The physicist, Boyle, as well as the anatomist, Lower, took an especially active part in these experiments. The blood of the same or of another species was used. The first transfusion in man was practised by Jean Denis in Paris in 1667 with lamb's blood. (a) The erythrocytes are the most important constituents to which the re- suscitating power of the blood is due. They retain their functions even after the blood has been defibrinated. The changes in the red blood-cells produced by time and by prolonged exposure to high temperatures have been described on p. 36. (6) With respect to the gases contained in the blood, it is to be remembered that oxygenated blood under no circumstance is injurious. Venous blood can, however, be infused into the blood-vessels of a living being without injury, provided the respiration is sufficient to arterialize the infused blood in its passage through the pulmonary capillaries. Under such circumstances the carbon dioxid contained in the blood is replaced by oxygen in the process of respiration. If the respiration, however, is arrested or if it is not carried on with sufficient activity, the blood, still rich in carbon dioxid, will be conveyed to the left heart and on through the arteries of the medulla oblongata. In consequence there results violent irritation of the centers in that region, followed later by paralysis and even by death. (c) The fibrin or the substances forming it take no part in the resuscitating activity of the blood. Therefore, defibrinated blood is capable within the body of assuming with equal success all of the functions that belong to non-defibrinated blood, (d) Investigations, especially by Worm-Muller, have shown that the vascular system (dog) is capable of taking up an excess of foreign blood up to 83 per cent., TRANSFUSION OF BLOOD. 19! without injurious consequences. It follows that the vascular system possesses to a certain degree the power of accommodating itself to large quantities of blood, just as it is known to possess the power of adapting itself to a diminished volume of blood, as, for example, after hemorrhage. Transfusion is practised: i. In cases of acute anemia, especially after a hemorrhage when it is sufficiently great to threaten the life of the patient. The object under such circumstances is to replace directly with new blood (from 150 to 500 cu. cm.) that which has been lost and is necessary to main- tain life. 2 . In cases of poisoning in which the blood has been vitiated by the admix- ture of a toxic substance and has thus become unfit to maintain the vital functions, a large quantity of this vitiated blood may be removed by copious venesection under suitable conditions and normal blood be introduced into the vessels in place ,of the blood withdrawn (depietory transfusion). The chief form of intoxication amenable to this treatment is that with carbon monoxid. Also the admixture of other poisons with the blood, especially those that dis- solve the erythrocytes or that cause marked methemoglobinemia, as, for ex- ample, potassium chlorate, as well as other toxic substances (ether, chloroform, chloral hydrate, opium, morphin, strychnin, snake-venom), may likewise furnish an indication to replace the poisoned mass of blood with normal blood. 3. Under certain morbid conditions, abnormal states of the blood may develop in the body and threaten its integrity; these may affect both the mor- phological elements, and the composition of the blood. The morbid alterations in the constitution of the blood include poisoning with urinary constituents (uremia) , with biliary constituents (cholemia) and with carbon dioxid. If severe they may cause death. Therefore, in desperate cases of this kind, especially when the cause is a temporary one, the vitiated blood may be in part replaced by normal blood. Whether hydremia, oligocythemia and pernicious anemia are indications for transfusion will depend on the correct interpretation of the under- lying disease. Between a quarter-hour and a half-hour after transfusion, in accordance with the amount of blood introduced, a more or less violent febrile reaction takes place. The operative procedure varies accordingly as defibrinated or non-defibrinated blood is employed. When a defibrination is to be practised, the blood obtained by venesection from a healthy human being is collected in a vessel and beaten with a small rod until the fibrin has been completely removed. The blood is then filtered through an atlas-filter, without pressure, is heated to .the tem- perature of the body by placing the vessel in warm water, and it is conveyed into the opened vessel with the aid of the buret-infuser of Landois or a syringe. The vessel selected may be a vein, as, for example, the basilic at the bend of the elbow, or the long saphenous vein at the internal malleolus. Under such circumstances the blood is injected in the direction toward the heart. The blood may be injected also into an artery (the radial or the posterior tibial), either in the centrifugal or in the centripetal direction. In any event, care must be exercised, especially when the blood is injected into the veins, to guard against the entrance of air, as such an accident might even cause death. Death occurs when the air that has entered the right heart is churned up into froth by the movements of the heart and in this form is pumped into the smaller branches of the lesser circulation, thus arresting the flow of blood through the lungs. After the injection of air into the arterial system a few small bubbles of air may possibly pass through the capillaries of the greater circulation and thus be found every- where in the vessels. They disappear at once, however, because the oxygen enters into chemical combination and the nitrogen is absorbed. If defibrinated blood is not to be infused the divided vein of the donor is connected by means of a tube with the vessel of the recipient, so that direct trans- fusion takes place. The blood may also be taken up with an oiled syringe, to which the blood does not adhere, and transfused at once without defibrination. The latter procedure, however, is attended with the great danger that coagula- tion may take place during the operation, in consequence of which blood-clots may readily be introduced into the circulation of the recipient. The resulting obstruc- tion and even more so the possible conveyance of coagula to the heart and into the lesser circulation, may even threaten life. Landois has transfused without injury into animals the non-coagulable blood that has been sucked by leeches after removal from them by stripping. From IQ2 TRANSFUSION OF BLOOD. the cephalic extremity of the leech hardened in alcohol, dried and pulverized, a decoction can be prepared by admixture with 0.9 per cent, saline solution (one head is boiled for ten minutes with 6 cu. cm. of a saline solution, and then filtration is practised). This decoction, when mixed in the proportion of 6 cu. cm. to 15 cu. cm. of blood obtained by venesection, suffices to maintain the latter in a fluid state. The mixture will not coagulate for some time and can be used without fear of injury. By this means the dreaded effect of the fibrin-ferment may be avoided. In Man the Infection of Animal Blood is Unjustifiable under Any Circumstances. Direct transfusion of blood from the carotid of a lamb into the brachial vein of a man was formerly employed not infrequently for therapeutic purposes. It is to be remembered, however, that the erythrocytes of the sheep are rapidly dissolved in human blood, and in consequence the most efficient constituents of the transfused blood are destroyed. In a general way, it is found that the blood- serum of many mammals has a rapid hemolytic effect upon the blood-cells of other species of mammals. Thus, the serum of dog's blood has a rapid and intense hemolytic action, while that of the horse and of the rabbit is relatively slow in action. The erythrocytes of mammals possess a variable power of resistance to the sera of other species of mammals. Thus, the erythrocytes of the rabbit, when mixed with the blood of another species, are readily dissolved; while the cells of the cat and the dog exhibit much greater resistance. The rapidity with which erythrocytes are destroyed in the blood of another species is proportional to the rapidity with which the blood-cells of the blood of the other species are dissolved in the blood-serum of the recipient. Thus, for instance, rabbit's blood and lamb's blood disintegrate within a few minutes in the circulation of a dog. When there is a difference in the size of the blood-corpuscles of the two species, the hemolysis can readily be observed in small specimens of blood obtained by puncture. As the erythrocytes dissolve, the blood-plasma is stained red by the liberated hemo- globin. A portion of this liberated material may supply the demands of metabo- lism in the body of the recipient and be utilized for katabolism and anabolism, while part of it is used up in the formation of bile. When, however, the quantity of hemoglobin liberated by the erythrocytes is considerable, hemoglobin is excreted in the urine, and to a less extent in the intestine, in the ramifications of the bron- chial tree and into the serous cavities. In the last the hemoglobin may subse- quently undergo absorption. Thus, in man hemoglobinuria has been observed after the injection of more than 100 grams of lamb's blood. When blood from another species is transfused into an animal, the blood-cor- puscles of the latter may undergo partial disintegration. This is the case when the erythrocytes of the recipient are readily soluble in the serum of the trans- fused blood. Upon this fact depends the great danger of transfusing a consider- able quantity of heterogeneous blood into the rabbit, whose erythrocytes so readily undergo solution. The same thing would happen if a dog's blood were transfused into the veins of a man. In animals whose erythrocytes readily un- dergo solution, as, for example, the rabbit, the injection of many kinds of sera, as, for example, that of the dog, of man, of the pig, of sheep, and of the cat, is followed by alarming symptoms, in accordance with the quantity of blood in- troduced, namely: acceleration of respiratory frequency to the point of dyspnea, convulsions, and even death from asphyxia. Under such circumstances all the stages of hemolysis can be seen in a specimen of blood obtained by puncture. Animals possessing more resistent erythrocytes, such as dogs, tolerate the injec- tion of heterogeneous sera, as, for example, from sheep, neat cattle, horses and pigs, without exhibiting such marked symptoms. The injected foreign serum, being of feeble potency, is disposed of in the circulation of the recipient, before it has time to attack, not to say dissolve, the blood-cells to any great extent. The process of hemolysis is accompanied by two other phenomena, which render the transfusion of heterogeneous blood especially dangerous: i. Before the erythrocytes are dissolved, they usually adhere together tenaciously and form small masses, consisting of from 10 to 20 or more blood-cells, which are obviously capable of obstructing large capillary areas. When these masses have been present in the blood for some time they yield up their hemoglobin, leaving only the fused remains of stroma. This forms a viscid, tenacious, stringy mass (stroma-fibrin) , which likewise may occlude the smaller vessels. 2. The sudden appearance of large quantities of dissolved hemoglobin in the blood of an animal may cause extensive coagulation, principally in the venous system, but also in the larger vessels throughout a considerable extent. The processes described may produce death either suddenly or after a protracted course. Dissolved hemoglobin causes THE DUCTLESS GLANDS. INTERNAL SECRETIONS. 193 in the circulation the dissolution of numerous leukocytes, from whose disintegration the fibrin-factors result. It is curious that hemoglobin exposed to the air gradually loses this property; also fibrin-ferment in contact with hemoglobin is gradually destroyed or rendered inactive. As numerous small vessels are occluded as a result of the processes described, the signs of impeded circulation and of stasis will be encountered in the different organs of the body. In man, the injection of lamb's blood is followed by a bluish-red dis- coloration of the skin. The obstacles encountered by the blood-current in the lungs cause dyspnea or even laceration of the small vessels in the air-passages and bloody expectoration. The dyspnea may increase if interference with the free circulation of the blood develops at the respiratory center. The digestive organs, for the same reason, exhibit increased intestinal peristalsis, diarrhea, evacuation of the bowels, tenesmus, vomiting and abdominal pain. These phenomena are explained by the fact that any disturbance of the circulation in the abdominal vessels is followed by increased peristaltic movements. In the kidneys secondary degeneration of the glandular substance takes place in consequence of occlusion of the vessels. The uriniferous tubules are occluded by casts consisting of coagulated albuminous material. In the muscles the occlusion of numerous vessels may 'cause stiffness, or even rigidity from coagulation of myosin, just as in Stenson's experiment, together with increased heat-production. Also the nervous system, the organs of special sense and the heart may exhibit various disturbances, all of which can be attributed to the occlusion of vessels and the resulting interference with the circulation. It is interesting to note that the transfusion of foreign blood is followed as a rule within half an hour by the development of active fever. Finally, it should be mentioned that lacerations of the vessel-walls have also been observed. These explain the obstinate hemorrhages that may occur not only on the free surfaces of mucous and serous membranes, but also in the parenchyma of organs, as well as in surgical wounds. The blood itself coagulates slowly and imperfectly. By far most of the facts bearing on the transfusion of heterogeneous blood that have been mentioned were discovered through Landois' investigations. Attempts to inject other substances instead of blood are not to be commended: from 0.75 per cent, to 0.9 per cent, saline solution, while capable of improving the circulatory conditions in a purely mechanical way, and thus exerting a favora- ble influence, is obviously incapable of supporting life in cases of severe anemia, in which the quantity of blood remaining in the body is insufficient to maintain the vital processes. THE DUCTLESS GLANDS. INTERNAL SECRETIONS. Within comparatively recent times there has been attributed to the ductless glands, whose activity is still, for the most part, shrouded in obscurity, a special and important function, namely, the production of substances that enter the circulation and there in some peculiar way excite certain activities, or render innocuous certain poisonous sub- stances generated in the process of metabolism, either by destroying these or by manufacturing an antidote. In a similar manner it has been asserted of a number of other organs in the body that, in addition to their special function, they exert an important influence on the economy- by means of such internal secretion. Thus, Brown-Se"quard and d'Ar- sonval asserted that the kidneys are in part concerned in rendering innocuous the toxic substances that accumulate in the body after nephrectomy; Tigerstedt and Bergman, that the kidneys produce a substance renin that increases the blood-pressure and has a powerful influence on the peripheral nerve-centers. The substances under consideration can be obtained from the corresponding organs in the form of extracts and their action can then be tested upon the animal body. The spleen is contained in a firm fibrous capsule, which at the hilus gives off an investment for the entering blood-vessels. From the inner surface of the cap- 13 194 THE DUCTLESS GLANDS. INTERNAL SECRETIONS. sule and the surface of the vascular sheaths there pass off numerous intersecting and branching trabeculae (the trabeculae of the spleen) , which form a rich mesh- work in the interior of the viscus, comparable to the cavities of a sponge. Fibril- lated connective tissue, mixed with elastic and unstriped muscle-fibers, forms the foundation of this portion of the viscus. The interior of the meshes contains a delicate reticulum of adenoid tissue (Fig. 131), which, together with the cellular elements contained in the meshes, is designated the splenic pulp. The smaller arterial branches, which gradually lose their fibrous sheath, ulti- mately break up into brush-shaped terminal twigs without anastomoses (peni- cils) . The points of division of the small arterial branches serve for the lodgment of the whitish Malpighian vesicles, which may attain the size of a pinhead and the structure of which in every respect resembles that of solitary lymph-follicles. The Malpighian bodies are found on examination to be spherical, lymphatic masses that have partially separated from the vascular sheath. In some animals, instead of exhibiting a spherical form, they appear as loose arterial sheaths, in a measure as perivascular lymphatic sheaths, so to speak, which may extend to the smallest arterial twigs. According to Tomsa, lymphatic vessels coming from the Malpigh- ian vesicles are found in the subsequent course of the arterial sheath as far as the hilus of the spleen. Other lymphatics form a network in the capsule. With regard to the connection between the ends of the arteries and the veins, it is supposed that there is no continuous channel between the smallest capillary ar- terial twigs and the smallest venous branches and that the meshwork of the pulp- reticulum represents an intermediate vascular area devoid of walls. The blood, accordingly, passes through the meshwork of the spleen traversed by the reticu- lum, just as the lymph-stream passes through the spaces of the lymphatic glands. According to another view, there is really a closed vascular channel connecting the ultimate arterial and the corresponding venous capillaries, which, however, con- sists of dilated spaces (like the cavernous spaces in erectile tissues) . These inter- mediary spaces are, however, completely surrounded by spindle-shaped endothe- lium. Within the meshes of the reticulum are found cellular elements of various kinds: (i) White blood-corpuscles of various sizes, some swollen and filled with a granular material; (2) leukoblasts or embryonal forms of leukocytes, which multi- ply by division; (3) erythrocytes ; (4) embryonal forms of the latter, also desig- nated erythroblasts, which multiply by mitosis; (5) so-called blood-corpuscle-con- taining cells. The numerous nerves of the spleen consist of so-called Remak's fibers; they are sensory, motor, and vasomotor. Of the chemical constituents there should be mentioned globulin and nucleo- albumin, nucleinic acid, leucin, tyrosin, xanthin, hypoxanthin, taurin; further lactic, butyric, acetic, formic, succinic, uric, and glycero-phosphoric (?) acids; as well as fats, cholesterin, a gluten-like body, glycogen, inosite, iron-containing pigments, and even free iron oxid. The pulp becomes black on addition of ammo- nium sulphid. The ash is rich in phosphoric acid and iron, but poor in chlorin- combinations. With respect to the function of the spleen, the following points are note- worthy : 1. The spleen may be removed without injury to the individual, as has been proved both in animals and in man (more than QO cases, with about 40 recoveries). After removal of the spleen the hematopoietic activity of the bone-marrow appears to be increased. In frogs, extirpation of the spleen has been observed to be fol- lowed by the appearance of brownish-red nodules in the intestine, which have been regarded as vicarious spleens. Tizzoni speaks of splenic neoplasms in the omentum (horse, dog) after obliteration of the parenchyma and blood-vessels of the spleen. In extremely rare cases total absence of the spleen has been observed in man. 2. By virtue of its unstriped muscle-fibers the spleen is capable of undergoing change in volume. Irritation of the spleen or of its nerves (by heat or electricity, by quinin, eucalyptus, ergot, and other agents) causes diminution in the size of the viscus, with anemia and granular change. As the spleen is found to be en- larged a few hours after digestion, at a time when the digestive organs have per- formed their work and contain less blood, the spleen has been regarded as an apparatus for the regulation of the vascularity of the digestive organs. According to Roy the circulation in the spleen is dependent not alone upon the blood-pressure in the splenic artery, but in marked degree on the contraction THE DUCTLESS GLANDS. INTERNAL SECRETIONS. 195 of the unstriped muscle-fibers of the capsule and the trabeculae, and which manifests itself in rhythmical movements lasting one minute. Paralysis of the splenic nerves, as in connection with certain febrile intoxica- tions (malarial fever, typhoid fever), causes enlargement of the organ. Division of the nerves has the same effect. After extirpation of the small nerve-trunks scattered in the hilus Landois has observed circumscribed enlargement of the organ, with bluish-red discoloration. 3. The spleen has been regarded as a hematopoietic organ. In favor of this view is the fact that after extirpation the erythrocytes are diminished; further, the fact that a splenic infusion (or decoction, also an infusion of bone-marrow), when injected under the skin or into the peritoneal cavity, causes an increase of the erythrocytes. The spleen is also a breeding-place for leukocytes. The blood from the splenic vein always contains numerous leukocytes, many of which are subse- quently destroyed in the circulation. Bizzozero and Salvioli discovered that a few days after great loss of blood the spleen became swollen, and the parenchyma was found to be rich in nucleated embryonal erythrocytes. 4. Other investigators regard the spleen as an organ for the destruction of blood-corpuscles, the presence of so-called "blood-corpuscle-containing cells" par- ticularly supporting such a view. These cells are large leukocytes that have taken up red blood-corpuscles after the manner of phagocytes (similar cells are found also in extravasations of blood) . The red blood-cells gradually undergo degenera- tion within the leukocytes and yield as derivatives of hemoglobin iron-containing pigments resembling hematin. The spleen, therefore, contains more iron than can be accounted for by the amount of unaltered blood it contains. If with this fact there be yet compared the occurrence in the spleen of disintegration-products and of higher oxidation-products of the albuminous bodies, the spleen may prop- erly be regarded as an organ for the destruction of erythrocytes. Additional sup- port for this view is found in the appearance of the salts of the red blood-corpuscles in the splenic juice. According to Schiff, extirpation of the spleen has no effect on either the absolute or the relative quantity of the red and white blood-cor- puscles. Even in the normal state the spleen exhibits frequent changes in size in the course of the day, particularly in conformity with varying activity of the digestive organs. In this respect the spleen resembles the arteries. Its vasomotor nerves have their center in the medulla oblongata. Stimulation of that center, especially by asphyxia, causes contraction of the spleen. From the center fibers pass through the spinal cord (which is said to contain between the first and fourth cervical verte- brae ganglionic cells that likewise influence the contraction of the spleen) , further through the left splenic nerve and the semilunar ganglion into the splenic plexus. Irritation of the nerves, as well as the direct application of cold to the spleen or even to the splenic region, causes contraction of the viscus. Paralysis of the nerves, by curare or by protracted narcosis, causes enlargement of the spleen. Apparently only the peritoneal investment contains sensory nerves. Pressure on the splenic vein causes slight enlargement of the spleen. In har- mony with this fact is the observation that increased blood-pressure within the splenic vein (in the presence of portal congestion or after the cessation of hemor- rhoidal or menstrual bleeding) is frequently attended with splenic enlargement. The injection of splenic extract has an effect opposite to that of injection of suprarenal extract. The thymus gland is relatively well developed during fetal life and continues to grow during the first two years of life; but about the tenth year it becomes stationary in size and later degenerates to form the so-called thymic fat-body, the tissues of which still contain the remains of the lymphoid thymus-parenchyma. As long as it persists, the thymus appears to have the function of a lymph-gland; for in the embryo, which possesses no lymph-glands, it is functionally active, and in reptiles and amphibia, which also possess no lymph-glands, it is a permanently functionating organ. The thymus consists of acini varying in size from 0.5 to 1.5 mm. and possessing the structure of simple lymph-follicles. The lymph-cells lying within the reticulum may exhibit various stages of disintegration. In addition, there are found scattered through the organ peculiar and mysterious concentric bodies, especially during the time of involution. Numerous small lymph- vessels in part traverse the interior of the organ and in part spread out upon its surface. Blood-vessels are relatively numerous. Among the chemical constituents there should be mentioned in addition to 196 THE DUCTLESS GLANDS. INTERNAL SECRETIONS. gelatin, albumin, sodium albuminate, sugar and fat leucin, thymus-nucleinic acid r xanthin, hypoxanthin; formic, acetic, butyric, lactic, and succinic acids. In the ash, potassium and phosphoric acid preponderate over sodium, calcium, magnesium (ammonium ?) , chlorin, and sulphuric acid. Extirpation of the thymus gland in the frog is fatal. According to Svehla the infusion of thymus juice causes a fall of blood-pressure and acceleration of pulse, while large doses are fatal. The thyroid gland is an organ provided with vasomotor and secretomotor nerves, and composed of a richly cellular connective-tissue framework, containing closed circular or oval acini (from 0.04 to o.i mm. in diameter), which in the embryo and the new-born are lined with a single layer of nucleated, granular, cuboidal cells. In 50 per cent, of all subjects accessory thyroid glands, up to four, are associated with the main gland; a small detached gland is occasionally found in front of the descending aorta. In addition, accumulations of epithelial cells are found in the acini and, in embryos, also beneath the common capsule. From birth the cells secrete a colloid substance by a transformation of their proto- plasm, at the same time undergoing morphological changes. Some of the cells are destroyed in this process of colloid degeneration. The acini of the thyroid gland evacuate their contents in part by rupture, with destruction of the epithelium, in part, in the process of pure colloid-produc- tion, by secretion into the intercellular interstices; and in this way the secretion reaches the interfollicular lymph-spaces and then the blood. Blood-vessels of considerable size and importance enter the organ. Lymph- vessels partly begin in the interior among the acini, and partly form a network in the capsule that surrounds the entire organ. The constituents of the thyroid gland are colloid, nucleoalbumin, iodothyrin, leucin, xanthin; lactic, succinic, and volatile fatty acids. According to Schiff, Zesas, J. Wagner and others, extirpation of the thyroid gland is followed by death, with the symptoms of chronic intoxication. Dysphagia, vomiting and digestive disturbances, acceleration of the breathing; later dyspnea, alteration of the action of the heart, somnolence, slow and hesitating movements with fibrillar twitchings, which may go on to intermittent tonic convulsions (tetany) , palsies, alterations in cutaneous sensibility, desquamation of the skin, lowering of the body-temperature and of the blood-pressure, are the symptoms that precede death. Albuminuria, reduction of the amount of oxygen in the arterial blood and degenerations in the central and peripheral nervous system were observed by Albertoni and Tizzoni, Langhans, Kopp and Capobianco. In man, also, total extirpation of the thyroid gland (cachexia strumipriva) is a serious matter and often terminates fatally from tetany. The morbid phenomena may be counteracted, at least temporarily, by the internal administration of fresh or dry thyroid-gland substance, or by the sub- cutaneous injection of thyroid-gland extract or iodothyrin. The symptoms may be prevented by grafting a thyroid gland successfully in some other portion of the body, and permitting the organ to form adhesions. These facts prove that the thyroid gland produces a substance that is indispensable for normal metabo- lism. Stated more accurately, the function of the thyroid gland is to neutralize a substance produced in the body, the accumulation of which has a toxic influence on the nervous system. The accessory thyroid glands and the hypophysis appear to possess similar functions: they undergo compensatory hypertrophy after extirpation of the thy- roid gland. Other investigators attribute the condition known as myxedema, that is, mucoid infiltration of the subcutaneous tissues of the head and neck, with profound disturbances of the nervous system, to the point of idiocy, to loss of the function of the thyroid. Especially noteworthy is the enlargement of the thyroid gland, together with the palpitation of the heart and protrusion of the eyeballs, in the condition known as exophthalmic goiter, which appears to be due to simultaneous (toxic ?) irritation of the accelerator nerve of the heart, the sympathetic fibers of the unstriated muscles in the orbit and in the eyelids, as well as of the dilator nerves of the vessels of the thyroid gland. Myxedema and exophthalmic goiter seem to stand in a certain antagonistic relation to each other, the former depending on diminished, the latter on augmented, activity of the thyroid gland (hence extirpation has been recommended in cases of exophthalmic goiter). Landois observed in dogs that had been fed on thyroid glands a marked increase in the number and force of the cardiac contractions. The ingestion of thyroid gland causes an increased con- THE DUCTLESS GLANDS. INTERNAL SECRETIONS. 197 sumption of oxygen and therefore a more rapid breaking down of the tissues (for which reason it is a familiar therapeutic procedure for reducing weight) . According to Schondorff the body-fat is first transformed, the albumin not being attacked until the fat has been reduced to a certain minimum. The substance (solely?) active in this connection is iodothyrin, a body prepared in 1896 by Baumann, and con- taining nitrogen, phqsphorus, and iodin. In some localities marked enlargement of the thyroid gland (goiter) is quite common, and is not infrequently associated with idiocy and cretinism. In those cases in which the goiter is designated a follicular hyperplasia of the thyroid gland, the condition can be made to disappear by the administration of preparations of the thyroid gland. Fr. Hofmeister found, after extirpation of the thyroid gland in rabbits, degeneration in the cartilages and disturbances in the growth of the bones. According to Gegenbaur the thyroid gland is an actively functionating organ in some of the remote orders of animals (for example, among the tunicates, in which it appears as a groove and secretes a digestive juice) , which in vertebrates has undergone involution. The suprarenal bodies consist of a medullary and a cortical layer, and contain compartments formed by connective tissue and bounded by blood-vessels. In the cortical layer the compartments are oblong and radiate, while in the medullary layer they are rather circular. The former contain (embedded in a reticulum) polyhedral, nucleated, protoplasmic cells without walls, the substance of which contains pigment and fat-granules, and is darker and more resistent than that of the medullary cells. The medullary layer contains also small and multipolar, large sympathetic nerve-cells. Both cortex and medulla are richly supplied with nerve-fibers. The blood-vessels are relatively abundant. The suprarenal bodies contain the constituents of connective and of nervous tissue, besides leucin, hypoxanthin, benzoic and taurocholic acids, taurin, inosite, fat and pigment-forming bodies. Of inorganic substances potassium and phos- phoric acid preponderate. The function of the suprarenal bodies is practically unknown. After extirpa- tion of one suprarenal body, the other undergoes hypertrophy to double its original size. Bilateral extirpation is followed by death, with the symptoms 'of poisoning and paralysis. These symptoms, however, do not develop if a small piece is allowed to remain. It appears, therefore, that the suprarenal bodies also are designed to destroy a poisonous substance in the body, which exhibits its injurious effects after extirpation of the glands. The injection of a watery extract of supra- renal body is said to arrest temporarily the toxic symptoms that make their appearance after extirpation. Injection of the extract obtained from the medullary substance of healthy animals (and which does not contain albumin and is soluble in alcohol) gives rise to marked contraction of the arteries and increase in blood-pressure, slowing of the pulse by central stimulation of the vagus, or even arrest of the auricles. After section of the vagi the heart again becomes more rapid and stronger, owing to the action of the drug on the substance of the heart itself. The extract has the same constricting effect on small blood-vessels and hence raises the blood-pressure. The splanchnic nerve contains vasodilator and secretory fibers for the organ. The breathing is superficial and accelerated. Large doses injected intravenously cause death through enfeeblement of the central nervous system, dyspnea, and cardiac paralysis. In frogs muscular paralysis results. Brown-Se"quard believed that one of the functions of the suprarenal bodies is to inhibit excessive pigment-formation. In agreement with this view, Tizzoni found, after extirpation of the organs (in rabbits), abnormal pigmentations, espe- cially on the lips, and Boinet in the blood and subcutaneous cellular tissues (of rats) . In conditions in which erythrocytes are dissolved and converted into pig- ment the suprarenal bodies are found to be especially rich in pigment. In the medullary layer a substance is formed that becomes brown when exposed to the air or brought in contact with alkaline tissues. In man the skin often presents a bronzed pigmentation (bronzed skin, Addison's disease) when the suprarenal bodies and their capsules have undergone (tuberculous) degeneration. _ In hemi- cephalous monsters the organs are atrophic, even when only the anterior halves of the hemispheres are absent. Hypophysis Cerebri. CoccygeaL Gland. Carotid Gland. But little is known concerning the function of the pituitary body. The posterior portion belongs to the infundibulum, and here the nervous elements are, to a large extent, displaced by connective tissue and blood-vessels; while the anterior portion represents a 198 COMPARATIVE. constricted off and modified part of the invaginated mucous membrane of the pharynx and contains glandular ducts with clear or dark cells. The extract ob- tained from the pituitary body contains iodin and causes an increase in the blood- pressure, which, however, is less than that caused by an extract of suprarenal gland; the heart-beat becomes slower and more forcible. The function of the coccygeal gland, which is situated at the extremity of the coccyx, is unknown. The carotid gland, which occurs in man and mammals, and contains a con- voluted plexus consisting of intricately anastomosing capillaries within an epithe- lioid cellular mass, supported by a reticulum, has been compared by Stilling to the suprarenal bodies. Its function is unknown. COMPARATIVE. The heart in fishes (Fig. 74, /) and in the gill-bearing larvae of amphibia is a simple venous organ, consisting of auricle and ventricle. The latter sends the blood to the gills, where it is arterialized, and passing to the aorta it is dis- I. FIG. 74. Diagrammatic Representation of the Circulation. 7. In Fish: A, auricle with the sinus venosus (5); V, ventricle; B, bulb of the aorta-, c, branchial arteries; i i, branchial vessels; D, branchiales veins; E, circulus cephalicus aortae; F, common aorta; G, caudal artery; H, ductus of Cuvier; /, anterior cardinal vein; K, posterior cardinal vein; 7_, caudal vein; M M, kidneys. II. In the Frog: 7, sinus venosus; 77, right auricle; 777, left auricle; IV, ventricle; V, common trunk of the aorta and bulb, giving off the following: i, pulmonary arteries; 2, arch of the aorta; 3, carotid arteries; 4, lingual arteries (5 carotid gland); 6, axillary arteries; 7, common aorta; 8, celiac artery; 9, cutaneous arteries; y, pulmonary veins; p p, lungs. 777. In Saurians: 7, right auricle with venae cavar, 77, right ventricle; 777, left auricle; IV, left ventricle; V, anterior common aorta; i, pulmonary artery; 2, arch of the aorta; 3, carotid arteries; 4, posterior common aorta; 5, celiac artery; 6, subclavian arteries; 7, pulmonary arteries; 8, lungs. IV. In Turtles: 7, right auricle with venae cavae; 77, right ventricle; 777, left auricle; 7 F, left ventricle, i, right aorta; 2, left aorta; 3, posterior common aorta; 4, celiac artery; 5, subclavian arteries; 6, carotid arteries; 7, pulmonary arteries; 8, pulmonary veins. tributed to all parts of the body, returning finally through the capillaries and the veins to the auricle. The amphibia (frog, II) have two auricles and one ven- tricle. From the latter there arises a single vessel, which, after giving off the HISTORICAL. 199 pulmonary arteries, becomes the aorta and supplies all the organs of the body. The veins of the greater circulation empty into the right, those of the lesser circu- lation into the left, auricle. Fishes and amphibia possess a dilated bulbus arterio- sus at the beginning of the aorta; and this is partly covered with strong muscular tissue. Among reptiles the saurians (///) possess' two separate auricles, but the two ventricles are only imperfectly divided. The aorta and pulmonary artery arise separately from the latter. The venous blood of the greater and the lesser circulation, which flows separately into the right and the left auricle, becomes mixed in the cavity of the ventricle. In some reptiles, however, the opening in the ventricular septum appears to be capable of (voluntary or reflex?) closure. The complete separation of the two halves of the heart in turtles is shown in Fig. IV. The lower vertebrates possess valves at the orifice of the vena cava, which are rudimentary in birds and in some of the mammals. All birds and mammals, like man, possess two separate auricles and two separate ventricles. In the halicore, a graminivorous marine animal resembling the whale, the ventricular portion of the heart is divided by a deep cleft into two halves. In bats the veins of the wings pulsate. The lowest of all vertebrates, the amphioxus, has no heart at all, but rhythmically contracting vessels. Of the ductless glands, the thymus and the spleen are found constantly in vertebrates. The latter is wanting only in the amphioxus and in a few fishes. Among invertebrates closed blood-channels with pulsating movements are only found occasionally, as, for example, in the echinoderms (sea-urchin, star-fish, holothurians) and in the higher worms. Insects possess in the dorsal region a central circulatory organ (the "dorsal vessel"), a contractile, longitudinal duct, capable, by virtue of its muscle-fibers, of dilating, and provided with valves which propels the blood rhythmically into the interstices of all the organs. Insects have no closed circulation. Shell-fish and snails have a heart and lacunar blood- channels. Cephalopods (sepia, cuttle-fish) have three hearts: an arterial, simple body-heart, and two venous, simple branchial hearts, one at the base of each gill. The circulation in most of these animals is closed. The lowest animals have either (multiple) pulsating vacuoles, which propel the colorless (blood-) juice into the soft body-parenchyma, like the infusoria; or they are totally devoid of any kind of vascular apparatus, the circulation of the juices being effected by the movements of the body (gregarines) . In the group of celenterates (polyps, jelly- fish) there is a "water-vascular system," which conveys the nutritive juice directly from the digestive cavity, and, at the same time, acts as a respiratory organ, as the water (which contains oxygen) passes through the system of tubes. HISTORICAL. The ancients (Empedocles, born 473 B. C.) were familiar with the movement of the blood, but were ignorant of the "circulation." According to Aristotle (384 B. C.) the heart, the acropolis of the body (which is present in every blood- animal), prepares the blood within its cavities and sends it through the arteries as a nutrient fluid to all the different parts of the body, like a system of constantly dividing brooks, irrigating the land and moistening and fertilizing it. The blood however, never flows back to the heart. Praxagoras (341 B. C.) named the "arteries" (as well as the trachea); he was the first to distinguish arteries from veins. Together with Herophi-lus and Erasis- tratus (300 B. C.) , trje famous physicians of the Alexandrian school, he is responsible for the erroneous view, based on the fact that arteries are empty after death, that the arteries contain air conveyed to them through the respiration (hence the name "artery"). Galen (131-203 A. D.) refuted this error by vivisection. "When- ever,", he says, "I injured an artery I saw blood escape. And when I tied a portion of an artery by means of two" ligatures at either extremity, I showed that the included portion was full of blood." Even then the theory of the exclusively centrifugal movement of the blood was maintained; it was erroneously supposed that communicating orifices existed in the septum between the right and the left heart. Miguel Serveto (a Spanish monk, who was burned as a heretic in Irene va i: 1553 at Calvin's instigation) was the first to show that the septum of the heart has no openings. He, therefore, searched for a communication between the right and the left heart and thus succeeded, in 1546. in discovering the lesser circulation: "fit autem communicatio haec non per parietem cordis medium (septum), ut vulgo 200 HISTORICAL. creditur, sed magno artificio a cordis dextro ventriculo, longo per pulmones ductu, agitatur sanguis subtilis; a pulmonibus praeparatur, flavus efficitur et a vena arteriosa (Arteria pulmonalis) in arteriam venosam (Venae puimonales) trans- funditur." Almost a quarter of a century later, in 1589, Caesalpinus traced the course of the greater circulation. He was the first to use the word "circulation." Later, Fabricius ab Aquapendente (Padua, 1574) also recognized and confirmed the centripetal movement of the blood in the veins (which until that time was almost universally believed to be centrifugal, although Vesalius was familiar with the centripetal current in the main trunks) from the position of the valves in the veins, of which he made an accurate study, although they had been men- tioned in the middle of the fifth century after Christ by Theodoretus, Bishop of Syria, also by Sylvius, by Vesalius (1534) and by Canani (1546) . William Harvey, a pupil of Fabricius (until 1604), finally constructed, between the years 1616 and 1619, partly from his own investigations and partly from the results of former observers, the picture of the circulation of the blood, the greatest physiological achievement, which was published in 1628 and marks a new epoch in physiology. With respect to individual features of the vascular system, the following is yet worthy of mention: According to Hippocrates the heart is a fleshy organ and the root of all the vessels ; he was familiar with the large vessels originating from the heart, the valves, the chordae tendineag, the auricles, and the closure of the semilunar valves. Aristotle first named the aorta and the venae cavae, the school of Erasistratus the carotid; the latter also explained the function of the venous valves. In Cicero mention is made of the distinction between arteries and veins. Celsus, in the fifth century after Christ, pointed out that the veins, when opened below a compressing bandage, bleed. Aretaeus (50 A. D.) knew that arterial blood is bright red and venous blood dark. Pliny (died 79 A. D.) described the pulsating fontanel in man. The presence of a bone in the septum of large mam- mals (ox, stag, elephant) was known to Galen (131203 A. D.). In his opinion the veins ultimately communicate with the arteries by means of the finest tubes, and this view was later confirmed by de Marchettis (1652) and Blancard (1676) with the aid of injections, and by Malpighi, who made microscopic observations of the circulation of the blood in cold-blooded animals, as well as by William Cowper (1697) , who made similar observations on warm-blooded animals. Stenson, who was born in 1638, first demonstrated the muscular nature of the heart, al- though a statement to like effect had already been made by the Hippocratic and Alexandrian schools. Cole demonstrated the progressive increase in the width of the arterial area as the capillary region is approached. Joh. Alfons Borelli (1608 1679) was the first to estimate the power of the heart according to the laws of hydraulics. Craanen, in 1685, described systolic contractions in the pulmonary veins;. Leeuwenhoeck (1694) the anatomical arrangement of the heart-muscle fibers among themselves. Chirac, in 1698, ligated a coronary artery of the heart in a dog, without, it is true, producing any result. According to Aristotle, turtles can live for a short time after the heart has been removed. Many of the ancients (the Israelites, Empedocles, Kritias, Lucretius) believed that the vital principle of the body, and even the soul (Aristotle and Galen) , had its seat in the blood. Aristotle was familiar with the poisonous effects of the vapor of burning charcoal; Porcia voluntarily chose to die by inhaling it. Vene- section was practised by Greek physicians soon after the Trojan war. The iron in the red blood-corpuscles was discovered by Menghini in 1746. PHYSIOLOGY OF RESPIRATION. OBJECTS AND SUBDIVISIONS. The purpose of respiration is to convey to the body the oxygen necessary for its oxidation-processes, as well as to remove the carbon dioxid resulting from the combustion processes. The activity required for this purpose is most effectively rendered by the lungs. A distinction is made between external and internal respiration. The first embraces the exchange of gases between the outer air and the gases of the blood contained in the respiratory organs (lungs and skin) ; the second in- cludes the exchange of gases between the capillary blood of the systemic circulation and the body tissues. STRUCTURE OF THE AIR-PASSAGES AND THE LUNGS. The lungs are compound tubular (grape-like?) glands that secrete carbon dioxid, and each of which sends its excretory duct (bronchus) to the common air- passage, the trachea. The trachea has for its foundation a number of C-shaped, superposed, hya- line, cartilaginous arches, held together by a rigid fibrous membrane of closely woven elastic network, intermixed with connective tissue, arranged principally in a longitudinal direction. The cartilages serve the function of keeping the lumen of the tube patulous under the varying pressure-relations. They subserve a similar purpose in the bronchi and their branches. They do not occur in air- passages having a diameter of i mm. or less; and even in bronchioles of greater size they are less numerous and more irregular, occurring especially at the bifurca- tions in the form of irregular platelets. An outer layer of connective and elastic tissue covers the air-passages and branches of the bronchial tree. On the side toward the esophagus this layer is reinforced by additional elastic elements and a few bundles of longitudinal un- striated muscle-fibers. The trachea contains unstriated muscle-fibers, especially arranged transversely, connecting the ends of the cartilaginous arches posteriorly and being inserted into the cartilages by means of elastic tendons. This transverse layer is again covered by longitudinal bundles. The mucous membrane, besides containing connective tissue and leukocytes, is especially rich in longitudinal elastic fibers, which attain their greatest size immediately beneath the epithelial basement membrane. The outer, narrow, scarcely separable submucosa is com- posed principally of connective tissue, and attaches the mucous membrane to the cartilages with their connecting fibrous membrane. The epithelium of the trachea is a stratified, ciliated epithelium, with the cilia waving toward the glottis, and with many interspersed goblet-cells. Numerous branched, tubular, mucous glands, with larger, brighter cells and smaller, darker ones (Gianuzzi's crescents) are founxl beneath the muscular layer of the trachea and bronchi. These glands are of a mixed type and have secretory ducts connected with their serous alveoli, but not with the mucous tubules. They secrete the viscid mucus that catches the dust -particles of the inspired air and is then removed from the bronchial tree and larynx by means of the ciliated epithelium. The air-passages are richly supplied with lymph-vessels and lymph-follicles, but are rather poor in nerves and blood- vessels. Ganglia are found on the nerve-trunks. The direction in which the branches of the bronchi penetrate into their respec- tive lobes corresponds with the inspiratory movement of the chest-wall covering each lobe; for example, the direction of the bronchi in the upper lobe is upward, forward, and outward. The small bronchi are distinguished from the larger ones by a diminution in 201 2O2 STRUCTURE OF THE AIR-PASSAGES AND THE LUNGS. the amount of cartilage, and by the presence of a complete layer of circular muscle- fibers; mucous glands are wanting, and the epithelium is less developed. Goblet- cells secreting mucus are found as far as the smaller air-passages. After the small bronchi have by repeated branching become diminished in diameter to from 0.5 to 0.4 mm., they are succeeded by the smallest bronchi, which already bear a few alveoli on their walls. The smallest bronchi still possess ciliated epithelium and unstriated muscle-fibers. The respiratory bronchioles are the direct continuation of the smallest bronchi. In the bronchioles the cylindrical epithelium is gradually replaced, at first on one side only, by small, squamous cells, and later by a mixed epithelium of large plates and small, squamous cells. At the same time the mural alveoli become more numerous. FIG. 75. Cross-section of Several Pulmonary Alveoli: A, alveolus with the blood-capillaries (c) that arise from larger vessels (g g) bounding the alveoli. B, the epithelium of an alveolus: i, nucleated cells; 2, non-nu- cleated platelets; 3, large, fused, non-nucleated plates. C, section of an alveolus with its epithelium and subjacent capillaries. D, alveolus, with its border covered by pulmonary epithelium and plates. E, alveolus whose boundary is indicated only by elastic fibers (f f). From these respiratory bronchioles there arise, finally, the blind, alveolar ducts, which are completely lined with mixed epithelium, containing the small, squamous cells only in small nests. The alveolar ducts subdivide further, and still contain a few isolated muscle-fibers in their walls. These subdivisions are entirely surrounded by numerous closely packed, hemispherical or spheroidal air-sacs (alveoli) . Concerning the structure of the alveoli, the following is to be noted (Fig. 75): (i) The supporting membrane of the sac is structureless, elastic, with enclosed nuclei. Fine pores in the walls of the septa connect neighboring alveoli. (2) Networks of numerous, fine, elastic fibers surround the air-sacs, and give to the pulmonary tissue its great elasticity. As the elastic fibers are characterized by STRUCTURE OF THE AIR-PASSAGES AND THE LUNGS. 203 considerable power of resistance, they are often found retaining their characteristic arrangement in the expectoration of patients suffering from pulmonary diseases. This is an infallible sign that the pulmonary tissue is undergoing destruction. (3) The branches of the rich capillary network pass rather toward the lumen of the alveoli. The respiratory epithelium of the alveoli is a single layer of squamous epithelium. In it may be found scattered nucleated, protoplasmic cells (i) , which are transformed later into small (from 7 to 15 //), non-nucleated, bright (2) or dark platelets. Finally, several of the latter unite to form larger (from 22 to 45 //) , non-nucleated plates. (3) Here and there incomplete fissures may be seen in these plates, which indicate previous interspaces between the platelets. The plates have been transformed from original cuboidal cells by the stretching of the lungs during respiration. See estimates the number of alveoli at 809^ millions, and their respiratory area at 81 square meters (54 times as great as the surface of the body). The alveoli are grouped together by connective tissue into distinct pulmonary lobules. The blood-vessels of the lungs belong to two distinct systems : A. The system of the pulmonary vessels (the lesser circulation) . The branches of the pulmonary artery follow those of the air-passages, and are so closely applied to the latter that their pulsations may be communicated to the contained air. The capillaries arising from these branches form a rich network of moderately fine tubules. The pulmonary veins, whose branches likewise accompany the air- passages, are collectively narrower than the pulmonary artery, as a result of the loss of water that the blood undergoes in the lungs. B. The system of the bronchial vessels conveys the nutrient material for the respiratory organs. The bronchial arteries, following the bronchi, give to them branches, as well as to the lymphatic glands at the hilus of the lungs, the large trunks of the pulmonary vessels (vasa vasorum), and the pulmonary pleura. Numerous anastomoses occur between the branches of the bronchial and pul- monary arteries. Part of the vessels arising from the capillaries communicate with the beginnings of the pulmonary veins ; and for this reason any considerable stagnation of blood in the lesser circulation causes a like stagnation in the circula- tion in the bronchial mucous membrane, with resulting bronchial catarrh. An- other part of the bronchial capillaries forms special veins, which, as bronchial veins, traverse the posterior mediastinum, and empty into the trunks of the azygos veins, the intercostal veins, or the superior vena cava. The veins from the smaller bronchi, and even from the bronchi of the fourth class, empty collectively into the pulmonary veins ; and the anterior bronchial veins also communicate with the pulmonary vessels. The interstitial tissue of the lungs is rich in lymphadenoid tissue and is traversed by a network of fine lymph-channels. A coarser, irregular system of lymph- vessels surrounds the pulmonary lobules, larger bronchi, and blood-vessels. These lymph-channels and vessels become injected when animals are made to inhale powdered, soluble dyes. The coloring-matter penetrates the viscid inter- stitial substance between the epithelium, though according to Klein through small pores that are present. In the walls of the pulmonary alveoli the finest lymph-tubules form a delicate system of canals lying in the spaces between the blood-capillaries. These canals exhibit enlargements at the points of intersection. Lymph- vessels extend along the bronchi, forming a dense, longitudinally meshed network in the mucosa and submucosa, and finally reaching the lymphatic glands at the roots of the lungs. The rapidity with which fluids are absorbed in the lungs, even when introduced in considerable quantities, is remarkable. Landois has often seen this after in- jecting water into the trachea of living animals, and Peiper has demonstrated it for many other substances. Even blood is taken up in like manner, Nothnagel having found blood-corpuscles in the interstitial pulmonary tissue from three to five minutes after injection into the trachea. In the pulmonary pleura, which is exceedingly rich in elastic fibers, the net- works of superficial pulmonary lymph-vessels begin as free stomata. In like manner the lymph-vessels of the parietal pleura communicate by means of sto- mata in many places (on the diaphragm only in certain localities) with the pleural cavity; according to Klein even with the free surface of the bronchial mucous membrane. The lymph, vessels of the veins of the lesser circulation lie between the media and the adventitia. The nerves of the lungs, bronchi, trachea, and larynx have ganglia. It appears that the function of the unstriated muscle-fibers in the trachea and 204 MECHANISM OF THE RESPIRATORY MOVEMENTS. in the entire bronchial tree is to offer resistance within the air-passages to the increased pressure that occurs in all forced expirations, as in speaking, singing, blowing, straining. According to the testimony of many investigators the vagus is the motor nerve ; upon it depends the so-called pulmonary tone when the tension within the air-passages is increased. Irritation of the vagus, or of the lung directly, does not induce sudden, expiratory movements (as can be seen by fastening a manometer in the trachea) . The only result of irritation of the vagus is an increase in the resistance of the air passing through the small bronchi that have been nar- rowed by the irritation. Section of the vagus also is said to increase the volume of the lungs. Atropin paralyzes, pilocarpin stimulates, the bronchial muscles of the dog, while reflex stimulation takes place through sensory branches of the vagus. During deepest inspiration the unstriated muscles of the air-passages con- tract, and during forced expiration they are relaxed. Pathological. Irritation of the unstriated muscles, causing spasmodic narrow- ing of the smaller bronchi, may give rise to asthmatic attacks. If the escape of air from the alveoli is thus made difficult or obstructed, an acute inflation of the lungs acute emphysema may result. According to Sandmann a reflex effect may be produced upon the bronchial muscles from the mucous membrane of the nose and the larynx. This would explain the occurrence of asthma attending nasal affections, such as polypoid growths of the mucous membrane. In addition to the elements of the connective, elastic, and muscular tissues, and of the mucous membrane, the lungs contain lecithin, inosite, uric acid (taurin and leucin in the ox; guanin (?), xanthin, hypoxanthin in the dog), also sodium, potassium, calcium, magnesium, iron oxid, considerable phosphoric acid, also chlorin, sulphuric acid, silicic acid, and carbon. In cases of diabetes sugar has been found; in the presence of purulent infiltration glycogen and sugar; in that of renal degeneration urea, oxalic acid, and ammonium-salts; in that of autointoxications leucin and tyrosin. MECHANISM OF THE RESPIRATORY MOVEMENTS. ABDOMINAL PRESSURE. The mechanism of breathing consists in an alternating dilatation and contraction of the thoracic cavity. The dilatation of the cavity is termed inspiration, and the narrowing expiration. The whole outer surface of both elastic lungs is, by means of its smooth, moist covering of pleura, intimately and hermetically applied to the inner surface of the chest- wall, which in its turn is covered by the parietal pleura. Hence, it is evident that every expansion of the thorax is accompanied by a corre- sponding expansion of the lungs, and every contraction compresses those organs. These movements of the lungs are, therefore, wholly passive, being dependent on the thoracic movements. By reason of their complete elasticity the lungs are able to follow every change in the capacity of the thorax, without causing the two layers of the pleura ever to separate. The cavity of the unexpanded thorax is greater than the volume of the collapsed lungs when removed from the body; therefore, the lungs in their natural position within the chest must be stretched, and they are, to a certain degree, in a state of elastic tension. This tension varies directly with the size of the thoracic cavity. If the pleural cavity be opened by a perforation from without or by a wound of the lungs from within, the elasticity of the lungs causes them to collapse, and there arises an air-space between the outer surface of the lungs and the inner surface of the thorax (pneumothorax). The affected lung is incapacitated for respiration. Double pneumothorax is accordingly fatal. The degree of the elastic traction of the stretched lung may be measured by introducing a manometer through an intercostal space into the pleural cavity of a dead body. The elastic tension here is the same as that in the living body dur- ing a state of quiet expiration, and is equal to 6 mm. of mercury. In a patient RESPIRATORY VOLUMES. 20 5 with perforation of an intercostal space Aron found the elastic tension to be from 4.5 to 6.8 mm. If, however, the thorax is, by force applied from the outside, brought into the expanded position assumed during inspiration, the elastic trac- tion will be increased to 30 mm. If the glottis be closed during inspiratory dilatation of the thorax, the elastic lungs also will expand, and there will be produced a rarefac- tion of the air within the lungs, as this air must expand to a greater volume. If the glottis is now suddenly opened, the atmospheric air will enter the lungs, until the density of the air within equals that of the atmosphere. On the other hand, if the chest and the lungs be com- pressed by expiratory efforts, with a closed glottis, the air in the lungs will become denser, that is, compressed into a smaller volume. If the glottis now be opened, air will escape from the lungs, until the internal and external pressures are equalized. As the glottis is open during ordinary respiration, the adjustment of the diminished or increased air-pressure during inspiration and expiration will occur gradually. It is certain, however, that there exists in the air within the lungs a slight negative pressure during inspiration and a slight positive pressure during expiration. This may be measured in the trachea of persons having wounds of this tube, and equals i mm. during inspiration and from 2 to 3 mm. during expiration. According to J. R. Ewald the total figures are only o.i mm. and 0.13 mm. respectively. The so-called abdominal pressure within the abdomen is generally increased during expiration, and declines during inspiration in man and in dogs, while in rabbits it is increased during inspiration. Moderate increase of the abdominal pressure increases somewhat the arterial blood-pressure, as well as the action of the heart; more pronounced increase of abdominal pressure diminishes both. RESPIRATORY VOLUMES. The lungs never completely empty themselves of air. Therefore, in filling and emptying the lungs during inspiration and expiration, only a part of the contained air is subjected to change, the amount depending on the depth of the respirations. Hutchinson in this connection established the following distinctions : i. Residual air is the volume of air that remains in the lungs after complete expiration. This can be estimated approximately after death by collecting over water the air from the lungs after ligating the trachea. H. Davy and Grehant estimated the amount during life in the following man- ner: The subject makes a forcible expiration, and then breathes for a while from and into a spirometer, filled with a measured quantity of hydrogen. If it can be assumed that the residual air has been completely admixed with the hydrogen, the percentage of air in the spirometer after forced expiration will indicate the quantity of residual air. The observers named found the amount to be from 1200 to 1700 cu. cm. Berenstein, by a similar method, estimated the residual air to be equal to from one-fifth to one-fourth of the vital capacity. The following wholly different method has also been employed to determine the residual air: The amount of an unknown volume of air x can be calculated from the increase in volume that it undergoes when the pressure upon it is lessened, for this increase in volume is directly proportional to the quantity of gas, and to the diminution in the pressure upon it. If Pj is the original pressure to which the gas is exposed, P 2 the other, lessened pressure, and d the measurable increase in volume of x, then x = (P 2 Xd) : (P! P 2 ). For carrying out this experiment Pfltiger constructed his pneumometer. The sub- 206 RESPIRATORY VOLUMES. ject is placed in a large, hermetically sealed chamber (human cabinet) , in which at first the pressure equals that of the atmosphere (P^. The contained air is then rarefied by means of a pump, until the pressure P 2 is obtained, as indicated by a manometer inserted in the chamber. In this process a part of the residual air (x) will naturally escape during quiet expiration. This is collected and meas- ured (d) by means of a spirometer connected in an air-tight manner with the air-passages. In this way Pfliiger found x to be from 400 to 800 cu. cm. Gad, working with different apparatus based on the same principle, estimates the residual air to be half the vital capacity; Schenck gives the proportion of the former to the latter as i to 3.7. 2. Reserve air is the additional volume of air that can be forced out after a quiet expiration. It measures from 1248 to 1804 cu. cm. The procedure of H. Davy and Grehant may also be applied to the estimation of reserve air. 3 . Respiratory or .tidal air is the volume of air that is taken in and given off during quiet respiration. In adults under normal conditions it amounts to about 507 cu. cm. between 367 and 699 cu. cm., according to Vier- ordt; in the new-born about one-quar- ter of this amount. 4. C omplemental air is the term ap- plied by Hutchinson to the additional volume of air that may be taken in during a forced inspiration immediately succeeding a quiet one. 5. Vital capacity indicates the vol- ume of air that escapes from the lungs between the highest phase of inspiration and the lowest phase of expiration. For Germans it amounts to 3222 cu. cm. on an average, and for Englishmen to 3772 cu. cm. From the foregoing it follows that after a quiet inspiration both lungs contain about from 3000 to 3900 cu. cm. of air ( i -f 2 -f- 3 ) ; after a quiet expi- ration from 2500 to 3400 cu. cm. (i -f- 2). From this, as from 3, it follows that during quiet respiration only about one-sixth or one-seventh of the air in the lungs is changed. If, during a series of quiet respirations, a solitary inhalation of hydrogen be made, and if the expired air be examined to determine how long the hydrogen may be detected in it, it will likewise be found that the air in the lungs com- pletely renews itself (becomes free of hydrogen) in from 6 to 10 respirations. Donders estimates that the combined bronchial tree and trachea contain about 500 cu. cm. of air. The vital capacity is determined by means of Hutchinson 's spirometer (Fig. 76). The determination is of importance in persons suffering from disease of the thoracic organs. The vital capacity may be influenced by consolidation, destruc- tion, or emphysema of the pulmonary tissue; by the presence of fluids, blood, air, or new-growths in the thoracic cavity; by diminished mobility of the chest; by weakness of the respiratory muscles ; by enlargement of the heart or pericardium ; or by distention of the abdomen. By means of a large tube provided with a mouth-piece, the subject (holding his nostrils closed) blows his expiratory air into a graduated gasometer bell- jar that is suspended over water and evenly balanced by a system of weights rand pulleys. FIG. 76. Hutchinson's Spirometer. THE RATE OF RESPIRATION. 207 After complete expiration the tube is closed, and the increase of air within the jar indicates the vital capacity, provided the water outside and that inside the jar are at the same level. It is also advisable to allow the expired air to cool, until it is of the temperature of the surrounding air. Of the factors that influence vital capacity the following are known: 1. Stature. Every inch of additional height between 5 and 6 feet is accom- panied by about 130 cu. cm. increase in the vital capacity. 2. The volume of ike trunk is, on the average, seven times that of the vital capacity. 3. The Body-weight. An increase in weight of 7 per cent, above the normal is accompanied by a diminution in the vital capacity of 37 cu. cm. for every additional kilogram. 4. Age. The vital capacity reaches its maximum at thirty-five years; from this up to the sixty-fifth year, and backward to the fifteenth year, 23.4 cu. cm. must be deducted for each year. 5. Sex. Arnold found the average to be 3660 cu. cm. for men, and 2550 cu. cm. for women. For the same stature and chest-measurement, the relation of the vital capacity of men to that of women is as 10 to 7. 6. Social position and occupation have a decided influence on the physical condition and nutrition, and hence also on the vital capacity. Arnold established three classes, of which each preceding class exceeds the one following by 200 cu. cm. greater vital capacity: (a) soldiers and sailors; (b) artisans, compositors, police; (c) paupers, the nobility, and students. 7. Miscellaneous. The vital capacity is greatest in the standing position, and when the stomach is empty. It is diminished after great effort, and also in de- bilitated conditions of the body. It is greater in advanced pregnancy than in the puerperium. To a certain extent practice with a spirometer can increase the vital capacity. THE RATE OF RESPIRATION. The rate of respiration varies in adults between 12, 16, and 24 in a minute. Four pulse-beats on an average thus occur with every respira- tion. Many factors influence the rate: 1. The Position of the Body. In adults Guy noted 13 respirations to the minute in the recumbent posture, 19 in the sitting posture, and 23 in the standing posture. 2. Age. In 300 individuals Quetelet found the rate of respiration to be as follows: Age. Respirations. Age. Respirations. Up to i year 44 Between 20 and 25 years 18.7 At 5 years 26 25 and 30 years 16 Between 15 and 20 years 20 3 and 5 years 18.1 In the new-born the rate is between 62 and 68. 3. Activity. In children between two and four years old, Gorham counted 32 respirations to the minute in the standing posture, and 24 during sleep. As a result of bodily exertion the rate of respiration increases before that of the heart-beat. The increase in respiratory movements is incited by metabolic products furnished by the muscles engaged in activity. In connection with violent muscular activity the pulse-rate is increased principally by excitation of the center for the cardio-accelerator nerves. 4. Increase in the surrounding temperature, also febnle elevation c the bodily temperature, will increase the rate of respiration, which may even assume a dyspneic character. THE TIME RELATIONS OF RESPIRATORY MOVEMENTS. PNEUMATOGRAPHY. In order to obtain information with regard to the periodic relations of the various phases of the respiratory movements, it is necessary 1 20 8 THE TIME RELATIONS OF RESPIRATORY MOVEMENTS. trace respiratory curves (pneumatograms) by means of recording in- struments. Method. The graphic method can be applied in three different ways : i . The representation of the range of motion in the individual parts of the thorax may be obtained in the following manner: (a) K. Vierordt and Ludwig arranged an instrument in which the movement of a definite part of the thorax was communicated to a lever, whose longer arm traced the curve on a rotating drum. In like manner Riegel constructed his double stethograph on the principle of the lever. It consisted of two levers on the same support, arranged for use on a patient in such way that one lever was applied to a certain spot on the healthy side of the chest, and the other lever to the corresponding spot on the affected side. A sphygmograph may be em- ployed for recording the respiratory curve, the instrument being placed free outside of the chest upon a stand and applied in such manner that only the pad of the elastic stylus touches the chest-wall at one point. J. Rosenthal constructed a lever to register the movements of the diaphragm in animals (phrenograph) ; it FIG. 77. A, Brondgeest's Air-cushion for Recording the Respiratory Curves. B, A Respiratory Curve of a Healthy Individual, Recorded on a Plate Attached to a Vibrating Tuning-fork (i vibration = 0.01613 sec.), to Deter- mine the Time-relations. was inserted through an opening in the abdomen, and rested against the dia- phragm. (b) The air-cushion of Brondgeest's pan sphygmograph (Fig. 77, A) is con- structed on the principle of air-transference. This instrument consists of a saucer- shaped brass vessel (a), over which is stretched a double-layered rubber mem- brane (b c) . Between the layers of this covering there is enough air to make the outer membrane bulge. This cushion is placed on a certain part of the thorax, and fastened with bands (d d) that pass around the chest. Every enlargement of the thorax presses against the membrane c, producing a diminution of the air- space within the capsule. The latter is connected by means of the tube S with the recording chamber that is pictured in Fig. 44 . Instead of this capsular arrangement, Marey, in the construction of his pneu- mograph, uses a piece of thick, cylindrical, elastic rubber tubing. This is fastened by bands like a girdle around the chest, and is connected by a tube with the recording drum. 2. The variations in the volume of the chest or in the exchanged respiratory gases may be graphically recorded as follows: For this purpose E. Hering places an animal in an air-tight, closed chamber, THE TIME RELATIONS OF RESPIRATORY MOVEMENTS. 209 with two openings in its walls. The trachea of the animal having been previously cut across, a cannula is fastened in the pulmonary end, and is attached to a tube passing through one of the openings in the chamber (respiration being conducted undisturbed through this tube) . Through the other opening passes a manometer- tube, filled with water, and pro- vided with a recording float. The same experiment may be conducted with a human subject, provided the breathing tube be placed in the mouth and the nose be held closed. Gad (Fig. 78) has succeeded in re- cording graphically the variations in the volume of the respired air by means of an apparatus: the expired air lifts a light, balanced box, which is closed off by water. In rising, this box moves a recording lever. During inspiration the box sinks. 3. The variations in the rapidity FIG. 78. Air-volume Recorder (Pneumoplethysmograph) with which the respiratory gases are (after Gad), changed may be recorded as follows : A tube is fastened in the trachea of an animal, or in the mouth of a human subject (holding the nostrils closed), in the same way as with the dromograph (Fig. 69) . The pendulum (made broader for this purpose) will swing to and fro during inspiration and expiration, and will record the velocity of the currents of air entering and leaving the lungs. FIG. 79.-Pneumatograms Recorded by Means of Riegel's Stethograph: /, normal curve; {. ]nsflrr , with emphysema; a, inspiratory limb, b t summit, c, expiratory limb of the curve. The small elevations are due to the pulsations of the heart. The curve in Fig. 77 B was drawn upon a vibrating tuning-fork plate, by means of the air-cushion of Brondgeest's pansphygmograph, applied to t form process of a health v man. The inspiration (ascending limb) beg moderate rapidity, is accelerated in the middle, and again becomes slower towar 14 210 TYPES OF RESPIRATORY MOVEMENTS. the end. The expiration begins with moderate rapidity, is then accelerated, and finally becomes much slower in the last part. Inspiration is somewhat shorter than expiration ; in adult males the proportion is 6 : 7, according to Sibson; in women, children, and old persons it is 6 : 8 or 6 : 9. Vierordt found the relation 10 : 14.1 (up to 24.1); J. R. Ewald found it n : 12. Cases in which inspiration and expiration are of equal length, or in which the latter is even the shorter, are observed only exceptionally. Small irregularities may be observed occasionally on various parts of the curve. These are due to the fact that the thoracic movements are at times the result of successive contractions of the respiratory muscles. Now and then power- ful heart-beats also cause vibrations of the thoracic wall (Fig. 79). If respiration proceeds uninterruptedly and quietly, there is usually no real pause, i. cd. On the left side of the figure it may be seen that when the rods are elevated, the line g h, representing the external intercostal muscles, is shortened (i k < gh) , while 1 m, representing the internal intercostals, is lengthened (1 m < o n). Fig. 81, II, shows that the intercartilaginous muscles, designated by g h, and the external intercostal muscles, designated by 1 k, are shortened by elevation of the ribs. The latter position of these muscular fibers may be represented by the shortened diagonals of the dotted rhomboids. The controversy over the mechanism of the intercostal muscles dates back to ancient times: Galen (131-203 A. D.) regarded the external intercostal muscles as inspiratory and the internal as expiratory muscles. Hamburger (1727), fol- lowing Willis' investigations, agreed with this view, and also recognized the inter- cartilaginous muscles as inspiratory muscles. A. v. Haller, who was Hamburger's direct opponent, considered both internal and external intercostals as muscles of inspiration; while Vesalius (1540) regarded them both as expiratory muscles. Masoin and R. du Bois-Reymond admitted the latter view, but only for forced respiration. Finally, Landerer, who observed that the upper two or three inter- costal spaces became narrower during inspiration, believed that both sets were active during both inspiration and expiration. As they hold the ribs together, they have the sole function of transmitting the traction imparted to them simply through the chest-walls. They would, therefore, remain active even when the distance between their points of insertion becomes greater. After mature consideration of all the conditions, Landois was unable to accept any of these views unconditionally. It is obvious that the external intercostal and intercartilaginous muscles can" act together only during inspiration, while the internal can be active only during expiration (the latter statement having been confirmed by Martin and Hartwell in dogs by means of vivisection) ; but elevation and depression of the ribs are not the chief results attained by the action of these muscles. It was rather Landois' opinion that the chief purpose of the external and intercartilaginous muscles is to counteract the inspiratory widening of the intercostal spaces and the synchronous increase in the elastic traction of the lungs. The function of the internal intercostal muscles is to offer resistance to the ex- piratory distention that occurs during, forced expiratory efforts, as in coughing. Without muscular resistance the intercostal tissues would be so stretched through the uninterrupted traction and pressure that regular respiratory movements would become impossible. The lesser pectoral (and the greater anterior serratus ?) is capable of assisting in the elevation of the ribs only when the shoulders are held in a fixed position, partly through a firm propping up of the arms, and partly by the rhomboid muscles, as is instinctively done by dyspneic patients. 216 ACTION OF THE INDIVIDUAL RESPIRATORY MUSCLES. 3. Muscles Acting upon the Sternum, the Clavicle, and the Spinal Col- umn. If the head be held in a fixed position by the muscles of the back of the neck, the sterno-cleido-mastoid can enlarge the thorax in an upward direction by raising the manubrium, together with the sternal extremity of the clavicle, thus assisting the scalene muscles. In like manner, but to a lesser extent, the clavicular insertion of the trapezius .may become efficient. A stretching of the dorsal portion of the vertebral column must result in an elevation of the upper ribs and a widening of the intercostal spaces, by means of which the inspiratory capacity is substantially in- creased. During deep inspiration this stretching is effected involuntarily. 4. In forced respiration every inspiration is accompanied by a descent of the larynx and a widening of the glottis. At the same time the palate is raised, in order to allow the air to enter with the least possible resist- ance. 5. Forced respiration is first made evident in the face by an inspiratory dila- tation of the nostrils (horse, rabbit). During marked dyspnea the cavity of the mouth is enlarged with each inspiration by a dropping of the jaw (gasping). B. Expiration. Quiet expiration is accomplished without muscular effort. It is, first of all, dependent principally upon the weight of the thorax, which has a tendency to fall back from its elevated position to the lower expiratory position. This is assisted by the elas- ticity of the various parts. When the costal cartilages are elevated, their lower borders are slightly rotated from below forward and up- ward, and their elasticity is thus brought into play. Hence, as soon as the inspiratory forces are relaxed, the cartilages return to their lower and no longer distorted expiratory position. At the same time, the elasticity of the distended lungs draws the thoracic walls, as well as the diaphragm, together on all sides. Finally, the tense, elastic ab- dominal walls, which become stretched and pushed forward, especially in men, return to their non-distended state of rest when the pressure of the diaphragm from above is released. It is self-evident that when the body is in an inverted position, the effect of the weight of the thorax is removed, and is replaced by the weight of the abdominal viscera pressing upon the diaphragm. Among the muscles that are brought into action only during forced ii FIG. 81. I, II. Diagrammatic Representation of the Mechanism of the Intercostal Muscles. DIMENSIONS AND EXPANSIBILITY OF THE THORAX. 217 respiration, the abdominal muscles stand foremost. They dimmish the size of the abdominal cavity, and thus press the viscera upward against the diaphragm. The triangular muscle of the sternum draws downward the sternal extremities of the united cartilages and bones of the ribs from the third to the sixth, which have been elevated during inspira- tion. The posterior inferior serratus depresses the four lowest ribs, the others necessarily following, being assisted by the quadratus lumborum, which is capable of depressing the last rib. According to Henle, how- ever, the posterior inferior serratus fixes the lower ribs so as to with- stand the pull of the diaphragm, thus aiding inspiration. Landerer even asserts that in the lower parts of the chest the movements of the ribs enlarge the thoracic cavity downward. In the erect posture and with a fixed spinal column, deep inspiration and expiration are accompanied by a displacement of the bodily equilibrium. During inspiration the center of gravity is moved slightly forward by the protrusion of the chest and the abdominal walls. In deep inspiration the straightening of the spinal column and the consequent throwing back of the head act as a compensation for the projection of the anterior trunk- wall. DIMENSIONS AND EXPANSIBILITY OF THE THORAX. It is of considerable importance for the physician to know the dimensions of the thorax, as well as the extent of its expansion in various directions. With inspiration the thorax is enlarged in all its diameters. The diameters of the thorax are determined by means of calipers; the circumference is measured by means of the centimeter tape-measure. In well-built men the upper circumference of the chest, close under the arms, measures 88 cm.; in women it is 82 cm. The lower circum- ference, at the level of the en- siform cartilage, is 82 cm. in men and 78 cm. in women. When the arms are held hori- zontally the measurement taken during expiration just below the nipples and the angles of the scapulae equals half the body-length, that is, 82 cm. in men; during deepest inspira- tion it is 89 cm. At the level of the ensiform cartilage the circumference is about 6 cm. less. In old persons the upper circumference is diminished, being smaller than the lower measurement. Usually the right half of the thorax is some- what larger than the left, on account of the greater muscular velopment. The longitudinal diameter of the thorax, from the clavicle to the lowest edge of the ribs, varies considerably. The transverse diameter (distance between the lateral surfaces, in men, from 25 to 26 cm., above and below; in women, from 23 to 24 cm. Above the nipples it is about i cm. greater. The antero-posteno diameter (measured from the anterior surface of the sternum t of a spinous process) is 17 cm. in the upper part of the thorax, and 19 cm. FIG. 82. Cyrtometer-curve from a Case of Left-sided Retraction of the Thorax in a Twelve-year-old Girl (after Eichhorst). 2l8 RESPIRATORY EXCURSION OF THE LUNGS. FIG. 83. Sibson's Thoracometer. in the lower part. Valentin found that during deepest inspiration in men, the circumference of the thorax at the level of the ensiform carti- lage increased between yV and y; Sibson found this increase to be yV at the level of the nipples. Various instruments have been devised to determine the degree of movement (elevation or depression) made by a definite part of the thorax during respiration. The cyrtometer of Woillez is quite useful : A measuring chain with stiffly movable links is applied to the outer sur- face of the thorax in a definite direction, for example, trans- versely at the level of the epi- gastrium or the nipples, or per- pendicularly through the mam- millary or the axillary line. In two places the links are loosely movable, permitting a removal of the chain without changing its form as a whole. The inner out- line of the chain is traced on a sheet of paper, and the form of the thorax is thus obtained (Fig. 82). If the instrument is first applied in the state of expiration, and then during inspiration, there is obtained a diagrammatic repre- sentation of the extent of move- ment in the various parts of the thorax. The same purpose is served by shadow-diagrams or photograms taken at the various periods of respiration. A compli- cated apparatus has also been constructed of numerous little rods, which rest on the thorax and rise and fall with the respiratory movement and can be fixed in a given position. The tkoracometer of Sibson (Fig. 83) measures the elevation of selected parts of the sternum. It consists of two metal rods, joined at right angles, of which one (A) is applied to the spinal column. On B is the movable arm C, which carries at its end the toothed bar (Z) directed perpendicularly downward. The latter is supplied with a spring, and ends below in a ball, which rests upon that part of the sternum to be investigated. The toothed bar, by means of a small cogwheel, moves the indicator (o) , which shows the excursions of the sternum on an enlarged scale. RESPIRATORY EXCURSION OF THE LUNGS. The boundaries and the size of the lungs in a state of rest on the ante- rior surface of the thorax are shown in Fig. 34. The shaded bounda- ries L L indicate the borders of the lungs, while the dotted lines P P show the extent of the parietal pleura (boundaries of the pleural cavity). In the living subject the extent of the lungs can be determined by percussion, that is, by striking the chest- wall (through an interposed thin plate of horn: Piorry's plessimeter) by means of a small cushioned hamrner (Wintrich's percussion-hammer). Wherever pulmonary tissue containing air lies in contact with the chest- wall, a sound is obtained like that produced by striking a vessel containing air (resonant per- cussion-note). Where the underlying parts contain no air, the sound is like that produced by striking the thigh (flat percussion-note). If the parts containing air are thin, or are partly deprived of their air, the note is dull. Fig. 84 in connection with Fig. 34 shows the boundaries of the lungs RESPIRATORY EXCURSION OF THE LUNGS. 2I 9 on the anterior chest-wall. The apices of the lungs extend above the clavicles anteriorly to a distance of from 3 to 7 cm. ; on the posterior surface they extend above the spines of the scapulae to the level of the seventh spinous process. On the right side the lower border of the lung, in a position of rest, begins at the right edge of the sternum at the insertion of the sixth rib, and extends horizontally outward to about the upper edge of the sixth rib in the mammillary line, and the upper edge of the seventh rib in the axillary line. On the left side (apart from the position of the heart) the lower border of the lung extends downward for the same distance. In Fig. 84 the line at b indicates the lower boundary of the lungs in a state of rest. Posteriorly, both lungs extend to the tenth rib. [Fio. 84. Topography of the Boundaries of the Lungs and the Heart during Inspiration and Expiration (after v. Dusch). During the deepest possible inspiration the lungs descend anteriorly below the sixth rib as far as the seventh ; posteriorly as far as the eleventh rib. At the same time the diaphragm withdraws from the wall of the thorax. During forced expiration the lower borders of the lungs rise almost for the same distance as they sink during inspiration. In Fig. 84 the line m n shows the limit of the border of the right lung during deep inspiration, and h 1 indicates the same border during complete expiration. The relation between the border of the left lung and the heart de- serves especial attention. In Fig. 34 may be seen an almost triangular space, extending to the left of the sternum from the middle of the inser- tion of the fourth rib to the sixth rib. This space represents that part of the heart which lies in direct contact with the chest-wall when the 220 NORMAL PERCUTORY CONDITIONS IN THE THORAX. thorax is at rest. Within these limits, represented by the triangle t t' t" in Fig. 84, percussion yields the cardiac dulness ; that is, a flat per- cussion-note is obtained here. In the larger triangle d d' d" a relatively thin layer of pulmonary tissue separates the heart from the chest-wall, and a dull note is obtained on percussion. Only outside this triangle is the so-called pulmonary resonance obtained. On deeper inspiration the inner border of the left lung passes completely over the heart, as far as the mediastinal insertion (Fig. 34), and thus the flat percussion-note is confined to the small tri- angle t i i'. On the other hand, during forced expiration the edge of the lung recedes so far that the cardiac dulness embraces the space t e e'. VARIATIONS FROM THE NORMAL PERCUTORY CONDITIONS IN THE THORAX. The investigation of the normal percutory conditions and their pathological variations is of the greatest importance for the physician. Suggestions of percus- sion (also of the abdomen) are found as far back as Aretaeus (81 A. D.). The real discoverer, however, is Auenbrugger (d. 1809), whose fundamental work was elaborated especially by Piorry and Skoda; the latter developed the physical theory of percussion (1839). Over the area of the lungs the otherwise clear, resonant percussion-note is impaired when the lungs have to a greater or lesser extent lost their normal air- content; an airless space of 4 sq. cm. on the outer surface of the lungs will yield a dull note. The note is impaired also when the lung is compressed from without. The percussion-note is louder or hyperresonant in lean individuals with thin chest- walls, or after deep inspiration, or in the condition of permanent expansion that occurs in emphysematous persons. It should also be noted whether the percussion-note is of high or of low pitch ; this quality being dependent to a certain extent on the degree of tension in the elastic pulmonary tissue, but especially on the tension of the thoracic wall. As this tension is increased during inspiration, and diminished during expiration, there should be recognized a corresponding difference in the pitch of the note. Deepest inspiration produces a higher pitch, on account of the increased tension of the chest-wall and the lungs ; but at the same time the note diminishes in dura- tion and intensity, as the more highly stretched parts possess a diminished ampli- tude of vibration. Sometimes in the terminal phase of the deepest possible in- spiration there occurs still another change in the percussion-note, in that there is produced, a certain restoration of the depth and intensity, falling short, however, of the original volume. During complete expiration the intensity is lessened and the pitch lowered. Percussion of the larynx and the trachea yields a clear tympanitic note, whose pitch depends upon the size of the cavity. The note is highest when the mouth and the nose are open, or when the tongue is protruded, or when straining efforts are made with closed glottis; it becomes lower when the head is extended back- ward, or during the act of swallowing, as well as during intonation. It is higher at the end of deep inspiration than during expiration. Affections of the lungs that lessen the normal tension lower the pitch of the note. When the percussion-note partakes of a drum-like character, approaching a musical sound, with distinguishable high and low pitch, it is termed tympanitic. If a hollow rubber ball applied to the ear be tapped with the finger, a typical tympanitic sound will result, the pitch of which is higher the smaller the diameter of the ball. Tapping the trachea in the neck will also yield a tympanitic note. The tympanitic note consists of a primary tone, together with several harmonic overtones, arising from an air-space surrounded by relaxed and movable walls (the non-tympanitic tone consists of the membrane-tone of a tightly stretched wall). The tympanitic note in the chest is always of pathological origin. It is found in the presence of a cavity within the lung-substance (when the mouth is closed, and especially when the nose is closed at the same time, the note becomes deeper), also in the presence of air in a pleural cavity, as well as in association with dimin- ished tension of the pulmonary tissue. The tympanitic note is closely allied to metallic tinkling, which arises in large, pathological, pulmonary cavities, as well THE NORMAL RESPIRATORY SOUNDS. 221 as when the pleural cavity contains air, when the conditions are suitable for a more uniform reflection of the sound-waves within the cavity. When a percussion- stroke is made over cavities, especially in the upper anterior part of the lung, the air at times escapes with a peculiar ringing and hissing sound the cracked- pot sound (or coin-sound). In practising percussion it should be observed by the sense of touch whether the underlying parts offer a feeling of greater or lesser resistance to the stroke ; and at the same time the vibratory power may be noted. Under normal conditions small vibratory power is associated with a well-developed bony framework, thick soft parts, and tense muscles. Pathologically, lessened vibration always occurs in connection with an airless condition of the lungs, and is associated with a dull percussion-note. Diminution of the resistance to the percussion-stroke is found normally in slender chests. Pathologically, it occurs when there is a considerable amount of air under the chest-wall, hence in the presence of pneumothorax and of abnormal expansion of the lungs by means of air. If the handle of a tuning-fork be placed upon the chest-wall, the fork will sound loud over spaces rilled with air, and will yield a weak note over spaces containing little or no air (Baas' phonometry). THE NORMAL RESPIRATORY SOUNDS. By listening over the chest- wall, either directly or by means of a stethoscope, the vesicular murmur can be heard during inspiration, wherever the lungs are in contact with the walls of the thorax. The character of this sound can be imitated if the mouth be placed in the position necessary for the act of sipping, and a sound between f and v be softly emitted. The sound is a sipping, rustling, hissing one. It is due to the sudden expansion of the pulmonary vesicles by the entrance of inspired air (hence the term vesicular) and also to the friction of the air passing through the alveoli. The sound is at times softer, at times louder. It is constantly louder in children under the age of twelve years, as the air- vesicles are one-third narrower than in adults, and cause greater friction with the entering air. During expiration the air, when leaving the vesicles, gives rise to a weak puffing sound of an uncertain soft character. The cardiopulmonary murmur heard in the vicinity of the heart when the latter contracts during systole likewise has a vesicular character. Bronchial breathing may be heard in the larger air-passages during inspiration and expiration, and resembles the sound of a loud, sharp h or sh. Outside of the neck (larynx and trachea) it may be heard be- tween the shoulder-blades at the level of the fourth dorsal vertebra (point of bifurcation), especially during expiration. It is somewhat louder to the right, on account of the larger caliber of the right bronchus. In all other parts of the thorax it is obscured by the vesicular murmur. The bronchial breathing arises entirely in the larynx, from the forma- tion of air- vortices, by reason of the marked constriction of the air- passage at the glottis. This laryngeal stenosis-sound causes a resonance of the tracheo-bronchial air-column, and thus produces the specific character of bronchial breathing, which the listener hears transmitted along the large tubes of the bronchial tree. It has been maintained that, if the air-filled lungs of an animal be applied to the neck over the larynx or trachea, the bronchial breathing produced there will become vesicular. In that case it must be supposed that vesicular respiration arises from a weakening and acoustic transformation of tubular respiration by r transference through the air- vesicles. Added to this is the fact that it is impos to produce any sound by forcibly driving air through narrow straws. 222 PATHOLOGICAL RESPIRATORY SOUNDS. During forced respiration rustling sounds often arise at the mouth and nostrils; with these sounds the primary tone of the oral cavity (usually the vowel-sound ah) is often mingled in mouth-breathing. PATHOLOGICAL RESPIRATORY SOUNDS. The recognition of the succussion-sound, the friction-sound, and many catar- rhal sounds dates back to Hippocrates (460-377 B. C.). The actual foundation of auscultation on a physical basis was laid by Laennec (1816), and its classical development is due to Skoda (1839). Bronchial breathing arises over the entire area of the lungs, either when the air-vesicles have become airless (through exudation) or when the lungs are com- pressed from without. In both cases the condensed pulmonary tissue conducts the bronchial respiration to the walls of the thorax. Bronchial breathing will also be heard over pathological cavities of considerable size that communicate with a large bronchus, provided the cavities lie sufficiently near the thoracic wall and have walls of considerable resistance. If there is no movement of air in the cavity, the sounds may be wholly conducted out through the trachea ; or during expiration a stenosis-sound (like that at the glottis) may arise in the communicating bronchus, and may be rendered amphoric by the resonant cavity. Amphoric breathing resembles the sound produced by blowing across the mouth of a bottle. It may arise when there occurs in the lungs a cavity at least the size of a fist, through which the air passes in such a manner that there is pro- duced the characteristic sound with a peculiar metallic echo. If the lung is partly expansible and contains air, and the pleural cavity also contains air, the resonance of the latter, together with the exchange of air in the lung, will also produce the amphoric sound. If the respiratory sounds have no definite character, so that they oscillate between vesicular and bronchial breathing, they are termed indefinite respiratory sounds. Frequently a deep respiration or expectoration of mucus will make the character of the sound more evident. If the air meets with resistance in its passage through the lungs, various phenomena may result: (a) At times the air- vesicles are not all filled simultane- ously, but intermittently. This occurs (especially at the apices) when partial swelling of the walls of the air-passages obstructs the steady interchange of air; cogwheel respiration is the result. Occasionally this is heard in perfectly normal lungs, when the muscles of the chest contract in an intermittent fashion, (b) If a bronchus leading to a pulmonary cavity is narrowed in such manner that the air meets with a temporary resistance, the inspiratory sound is at first like that of a loud G, and then goes over during the latter two-thirds of inspiration into a bronchial or amphoric sound. This is termed a metamorphosing sound, (c) Rales are produced in the larger air-passages when the air causes bubbling of the con- tained mucus. In the smaller air-spaces rales arise either when the walls of the latter are separated from the fluid contents during inspiration, or when their walls are in contact and are suddenly separated from each other. Rales are distinguished as moist (arising in watery contents) or as dry (in tough, tenacious contents) ; further, as inspiratory or expiratory, or continuous; also coarse, fine, or irregular rales, the high-pitched crepitant rales, and finally the metallic tinkling rales produced by the resonance of large cavities, (d) If the mucous membrane of the bronchi is so swollen or so covered with mucus that the air must force its way through, there arises frequently in the larger passages a deep humming purr sonorous rhonchus; and in the smaller tubes a clear whistling sound sibilant rhonchus. In cases of widespread bronchial catarrh a thrill may often be felt in the chest- wall bronchial fremitus caused by the numerous rales. When the lung is collapsed and the pleural cavity contains fluid and air, a sound may be heard on shaking the chest, similar to that produced by shaking a large bottle containing water and air the succussion-splash of Hippocrates. Rarely a higher-pitched similar sound may be heard in pulmonary cavities the size of a fist. When the opposed layers of the pleura are roughened by inflammatory processes, and rub against each other in the act of respiration, a friction- phenomenon is produced. This may be partly felt (often by the patient himself) and partly heard. The sound is usually creaking, and may be compared to that produced by bending new leather. Friction-sounds are produced also by the heart's action between the two layers of the diseased roughened pericardium. PRESSURE IN THE AIR-PASSAGES DURING RESPIRATION. 223 During loud speaking or singing the chest-wall vibrates vocal fremitus as a consequence of the propagation throughout the bronchial tree of the vibrations of the vocal bands. This vibration naturally is most pronounced in the region of the trachea and the large bronchi. If the ear be applied to the chest-wall the voice can be heard only as an unintelligible hum. If the pleural cavity contains air or a large effusion, or if the bronchi are occluded by large quantities of mucus the vocal fremitus is weakened or entirely absent. On the other hand all factors that cause bronchial breathing will increase the vocal fremitus. Hence the latter will be more marked also in those localities where bronchial breathing is heard even under normal conditions. The ear under such circumstances will hear the sounds conducted to the chest-wall with increased intensity. This is termed bronckopkony. If a pleural effusion or a pulmonary inflammation causes a flattening of the bronchi, the sound of the voice in the chest sometimes assumes a peculiar bleating quality egopkony. Doubtless the gradations of increased or diminished fremitus could be readily demonstrated by means of the sensitive flame (observed in a rotating mirror) or by the use of the microphone. For the former there should be employed an appa- ratus similar to the gas-sphygmoscope, with the lower part widened in the shape of a funnel. PRESSURE IN THE AIR-PASSAGES DURING RESPIRATION. If a manometer be fastened in the trachea of an animal in such a manner that respiration is not interfered with, the instrument will show a negative pressure 3 mm. of mercury) during inspiration, and a positive pressure during expira- tion. Donders has modified this experiment for man by introducing a U-shaped manometer-tube through one nostril, and instructing the subject to breathe quietly through the other nostril with the mouth closed. He found that during each quiet inspiration the mercury showed a negative pressure of i mm., and during each expiration a positive pressure of 2 or 3 mm. Aron experimented with patients having a tracheal fistula as the result of operation, and found during inspiration a pressure of from 2 to 6.6 mm. of mercury, during expiration from +0.7 to + 6.3 mm. of mercury. In speaking, the corresponding fluctuation was from 6 to + 7 , and when coughing from 6 to +46.1. As soon as the air is drawn in and expelled with greater force, the fluctuations of pressure become more marked, especially in the acts of speech, singing, and coughing. If forced respiration be practised with the mouth and one nostril closed, so that the respiratory canal communicates only with the manometer, the greatest inspiratory pressure is 57 mm. (between 36 and 74), and the greatest expiratory pressure is +87 (between 82 and 100) mm. Notwithstanding the higher expiratory pressure, it must not be inferred that the expiratory muscles are stronger than those of inspiration ; for during the latter act a series of resisting forces must be overcome, leaving a much diminished supply of force for the aspiration of the mercury. These resisting forces are: (i) The elastic tension of the lungs, which amounts to 6 mm. during complete ex- piration, but reaches 30 mm. during deepest inspiration. (2) The lifting of the weight of the thorax. (3) The elastic torsion of the costal cartilages. (4) The depression of the abdominal viscera and the elastic distention of the abdominal walls. All these resisting forces aid the expiratory muscles during expiration. With these facts in view, there is no doubt that the combined strength of the inspiratory muscles is greater than that of the expiratory muscles. As the lungs, by reason of their elasticity, have a tendency to collapse, they naturally exert a negative pressure within the thoracic cavity. In dogs this amounts to from 7.1 to 7.5 mm. of mercury during inspiration, while in expiration it is naturally less, namely only 4 mm. The analogous values obtained by different investigators on the dead body vary; Hutchinson fixes them at 4.5 mm. and 3 mm. The greatest pressure during inspiration and expiration seems small when compared to the blood-pressure in the large arteries. If, however, the pressure- values obtained for the respired air be estimated for the entire superfices of the thorax, considerable results are obtained. To measure the muscular respiratory power in case of illness, a U-shaped mercurial manometer may be employed, provided with an attachment suitable for introduction into a nostril or the mouth (Waldenburg's pnciimatomctcr} . The in- spiratory pressure alone may be reduced (in the presence of almost all diseases 224 MOUTH-BREATHING AND NASAL BREATHING. impairing the expansion of the lungs), or only the expiratory pressure may fall (in cases of emphysema and of asthma) , or both may be weakened (as occurs in feeble persons) . If a forced inspiration rarefies the air in the air-passages, the trachea and bronchi become narrowed and shortened; the reverse occurs during expiration. If a lung be inflated, air will steadily escape through the walls of the alveoli and trachea. The same thing takes pla'ce during violent expiratory efforts (cuta- neous emphysema attending whooping-cough) , so that pneumothorax, entrance of air into the blood-vessels, and even death may result. If a dog be made to breathe through Muller's valve, by means of which the resistance to respiration may be increased at will, it is found that a pressure of 40 cm. of water is still readily overcome, that a higher pressure can be overcome for a short time, and one of 70 cm. not at all. Until birth the airless lungs lie collapsed (atelectatic) in the chest-cavity, and fill it, so that pneumothorax is not produced if the thorax be opened in a dead fetus. Even in children that have lived for eight days and have breathed normally, the lungs do not collapse when the pleural cavity is opened, but remain in contact with the chest-wall. It is only after further growth that the thorax becomes so large that the lungs must expand under elastic tension; only then will opening of the thorax cause the lungs to contract into a smaller volume. Hermann calls attention to the fact that a lung containing air cannot be emptied by pressure from without. The reason for this is that the small bronchi will be closed by the pressure before the air can leave the alveoli. The muscles of expiration, therefore, have not the power to compress the lungs until they are airless; but, on the other hand, the inspiratory muscular power is sufficient to expand the lungs beyond the state of elastic equilibrium. Hence, the physical attributes of the lungs limit, to a certain extent, the mechanism of respiration: the muscles of inspiration expand the lungs and at the same time increase their elastic tension, while the expiratory muscles can only diminish the tension, without being able to abolish it altogether. MOUTH-BREATHING AND NASAL BREATHING. Quiet respiration is usually performed with the mouth closed, pro- vided the nose be unobstructed. The current of air passes through the naso-pharyngeal cavity, and there undergoes certain changes: (i) Its temperature is increased to the extent of -f of the difference between its original temperature and that of the body. (2) At this increased temperature it is saturated with aqueous vapor. These changes are made so that the cold, dry air does not irritate the lining of the lungs. (3) Dust-particles may cling to the mucus covering the irregular walls of the air-passages, and are again conveyed outward by the ciliated epithelium. The nasal secretion possesses qualities harmful to many bacteria (for example, anthrax-bacilli), thus demonstrating the salutary effect of nasal breathing when there is danger of contagion. (4) Finally, by means of the sense of smell bad air and air impregnated with injurious admixtures can be recognized. When the mouth is open no current of air passes through the nose during respiration. Pathological. Permanent obstruction of the nose, leading to exclusive mouth- breathing, may result in a long series of harmful effects; namely, catarrhal condi- tions of the pharynx, the air-passages, and the middle ear, abnormal formations in the bones of the mouth and the nose, pains in the facial muscles, changes in speech, disturbances of intellect (difficulty in fixing the attention). Another important phenomenon is the appearance of edema of the lungs; that is, an exudation of serum from the blood into the pulmonary alveoli. The causes of this condition are: (i) marked obstruction to circulation in the aortic system; for example, after ligation of all of the carotid arteries, or of the arch of the aorta in such a position that only one carotid remains pervious; (2) occlusion of the pulmonary veins; (3) cessation of action in the left ventricle (following mechanical injury), while the right ventricle still continues to beat. All of these causes will produce at the same time anemia of the brain, resulting in anemic MODIFIED RESPIRATORY ACTS. 22 5 irritation of the vasomotor center, and consequent contraction of the small arteries This will cause an increased amount of blood to enter the veins and the right heart, whose driving power increases the pulmonary edema. v. Basch believes that an overfilling of the pulmonary capillaries diminishes the elasticity of the alveoli, thus making the latter to a certain extent more rigid The expansibility, therefore, of the lungs is diminished. MODIFIED RESPIRATORY ACTS. There are a number of characteristic, partly involuntary, partly voluntary, variations of the respiratory movements, to which the not altogether suitable term abnormal respiratory acts has been applied. Coughing consists in a sudden violent expiratory effort, usually succeeding a deep inspiration and closure of the glottis, during which effort the glottis is sprung open, and any solid, fluid or gaseous substance that may be irritating the respiratory mucous membrane is expelled. The lips are parted during this act. It may be a voluntary or a reflex act, in the latter case being subject to the will only to a certain degree. Hawking consists in a rather long expiratory effort through the narrow space between the root of the tongue and the depressed soft palate for the purpose of removing foreign bodies. If the hawking be accomplished in an intermittent fashion, it is accompanied by a springing open of the glottis (mild, voluntary coughing) . This act is performed only voluntarily. Sneezing consists in a sudden expiratory effort through the nose, accom- panied by a sudden opening of the naso-pharynx, previously closed by the soft palate. The purpose is to expel mucus or foreign bodies. It is very seldom per- formed with the mouth open, and is preceded by a single or by repeated spas- modic inspiration. The glottis is always wide open. This act occurs only as a reflex through irritation of the sensory nerves of the nose, or as a result of a bright light suddenly falling upon the retina. The reflex may be to a certain extent inhibited by marked excitation of sensory nerves, such as rubbing the nose, or pressing the hyoid bone forcibly upward. Habitual use of nasal irritants, such as snuff, blunts the sensory nerves against reflex excitation. Coughing and sneezing rarely occur simultaneously. Snorting and Blowing the Nose ; Snuffing ; Sniffing. Noisy, forced breathing through the nose is designated snorting. Blowing the nose consists in a strong, noisy, expiratory effort made through nostrils that have been narrowed, either by the fingers or by the muscles of the nose and the upper lip, the object being to remove either foreign bodies or mucus. Snuffing consists of drawing substances up into the nose by a noisy inspiration, the mouth being closed, and the nostrils often being narrowed by the action of the muscles of the nose and the upper lip. Sniffing consists in drawing air up into the nose by a succession of short inspiratory efforts, for the purpose of smelling. The act is frequently accompanied by rustling noises and movements of the nostrils, while the mouth is held closed. All these actions are voluntary. Snoring results from breathing with the mouth open, the current of air during both inspiration and expiration causing noisy, vibrating movements of the relaxed soft palate. It usually occurs involuntarily during sleep, but it may also be produced voluntarily. Gargling consists in the noisy slow escape of the expired air in the form of bubbles through a mass of fluid held between the root of the tongue and the soft palate, while the head is thrown back. The act is voluntary. Crying is called forth by the emotions, and consists in short, deep inspira- tions, with prolonged expirations, the glottis being narrowed, and the muscles of the face and jaw being relaxed (with contraction of the zygomaticus minor) ; tears are secreted, and lamenting, inarticulate sounds are often emitted. In conjunction with intense, prolonged crying there often arise sudden, spasmodic, involuntary contractions of the diaphragm, which, when attended with valve-like approxima- tion of the vocal bands, give rise to the inspiratory sound known as sobbing. This act is purely involuntary. The sobbing that occurs so frequently during the agonal period may be explained by the electrical influence of the contraction of the heart on the phrenic nerves, which become highly irritable in the act of dying. Sighing is a prolonged respiratory movement, usually accompanied by a mournful sound, often aroused involuntarily by painful emotions. Laughing consists in a quick succession of short expirations through vocal 15 226 CHEMISTRY OF RESPIRATION. bands that are stretched for high notes, and are alternately approximated and separated, while characteristic, inarticulate sounds are emitted from the larynx, with vibrations of the soft palate. The mouth is usually open, and the face is drawn into a characteristic position by the zygomaticus major (not the risorius muscle). Laughing is usually aroused involuntarily by agreeable conceptions, or by feeble, sensory irritation, such as tickling. It may to a certain extent be repressed by the will, as by forcibly closing the mouth and holding the breath; also by painful irritation of sensory nerves, as by biting the tongue or the lips. Yawning consists in a prolonged, deep inspiration, with the mouth, the palatal arch and the glottis widely open, successively calling into play numerous inspiratory muscles. Expiration is shorter, and both are often accompanied by a prolonged, characteristic sound. There also occurs frequently a general stretching of the bodily muscles. The act is always involuntary, being usually incited by sleepiness or monotony. CHEMISTRY OF RESPIRATION. The problem here is to estimate qualitatively and quantitatively the gases expelled during respiration. If the results be compared with the gaseous composition of inspired, atmospheric air, a picture may be obtained of the interchange of gases occurring during respiration. QUANTITATIVE ESTIMATION OF THE CARBON DIOXID, THE OXYGEN, AND THE AQUEOUS VAPOR IN GASEOUS MIXTURES. Estimation of the Carbon Dioxid. The volume of carbon dioxid may be estimated by means of Vierordt's antkracometer (Fig. 85, II). The gaseous mixture is received and enclosed in a graduated tube r r, previously filled with water, and provided at one end with T[ FIG. 85. I. Apparatus for the Collection of Expired Air (after Andral and Gavarret). II. Carl Vierordt's Anthracometer. a bulb of known capacity. The bottle n, filled with a solution of potassium hydrate, is then screwed on the end-piece h. The stop-cock is opened, and the potassium-solution is allowed to run up into the tube, the latter being agitated METHODS OF INVESTIGATION. 22 7 until all the carbon dioxid is absorbed by the potassium, with the forma- tion of potassium carbonate. Then the solution is allowed to run back into the bottle, the stop-cock is closed, and the potassium-bottle is removed. The end of the tube is dipped into water, and the latter is allowed to rise in the tube. The volume of water thus admitted is equal to the volume of carbon dioxid removed by the potassium-solution. Determination by Weight. A considerable volume of the gaseous mixture is passed through Liebig's bulbs, filled with a solution of potassium hydrate and arranged in a combination such as that of Scharling's apparatus (Fig. 86, e, f, g). Determination by Titration. A considerable volume of the air to be exam- ined is conducted through a definite quantity of a known solution of barium hydrate. The carbon dioxid combines to form barium carbonate. The solution is then neutralized with a titrated solution of oxalic acid. The quantity of oxalic acid necessary to neutralize the remaining barium hydrate varies inversely with the amount of barium already combined with the carbon dioxid. Estimation of the Oxygen. The volume of oxygen may be determined in two ways: (a) By combining the gas with potassium pyrogallate. Vierordt's anthracometer may be employed for this purpose, substituting a solution of potassium pyrogallate for that of potassium hydrate. (6) By explosion in an eudiometer. Estimation of the Aqueous Vapor. The volume of air to be examined is allowed to pass either through a bulb- apparatus containing concentrated sulphuric acid, or through a tube filled with pieces of calcium chlorid. In both cases the water is energetically abstracted, and the increase in weight will give the amount of water in the air examined. METHODS OF INVESTIGATION. Collecting the Expired Air. If only the gases exhaled from the lungs are to be collected, the bell-jar of the spirometer (Fig. 76) may be used, suspended in a concentrated solution of sodium chlorid to limit the gas-absorption. Andral and Gavarret permitted several successive expirations to be made into a large bell- jar (Fig. 85, I, C). For this purpose a mouth-piece M was applied in an air-tight manner over the mouth, the nostrils being closed; the direction of the air-current was regulated by FIG. 86. Respiration Apparatus of Scharling. means of two so-called Muller's mercurial valves (a, b), which allowed the air to pass only in the direction of the arrows. If the gases given off from the skin during perspiration are to be investigated, as well as those from the lungs, then the subject must be placed in a closed cham- ber, from which the gases may be withdrawn for experimental purposes. The Most Important of the Respiration Apparatus. (a) The apparatus of Schar- ling (Fig 86) consists primarily of a closed chamber A, capable ot contain: a human being. The chamber has an afferent opening z, and an efferent opening b. The latter is connected with an aspirating contrivance C, consisting of a g< sized barrel filled with water. It is evident that when the water flows out ot the 228 METHODS OF INVESTIGATION. barrel, an uninterrupted stream of fresh air enters the chamber A, and the air in the chamber, mixed with the respired gases, escapes toward the barrel. Con- nected with the afferent opening z is a set of Liebig's bulbs d, filled with a solution of potassium hydrate through which the entering air passes and is deprived of its carbon dioxid, so that the subject breathes air completely free of carbon dioxid. Upon leaving the efferent opening b the air is first conducted through the tube e, in which the aqueous vapor is absorbed by sulphuric acid, and its amount may be determined by the increase in the weight of the tube. Then the air passes through the potassium-bulbs f, where all the carbon dioxid is absorbed. The tube g, filled with sulphuric acid, is intended for the purpose of absorbing the aqueous vapor conveyed by the air from f . The increase in weight of f -f- g represents the weight of the absorbed carbon dioxid. The volume of air inter- changed may be estimated from the contents of the barrel. (6) Regnault and Reiset's apparatus (Fig. 87) consists of a bell- jar R, in which is placed the animal (dog) to be experimented upon. Surrounding this CaCh FIG. 87. Diagrammatic Representation of Regnault and Reiset's Respiration Apparatus. jar is a cylinder g g, which may be used for calorimetric observations, a thermometer t being introduced for this purpose. The bell-jar has leading into it the tube c, through which is introduced a measured quantity of oxygen (Fig. 87, O), which (Fig. 87, CO 3 ) has given off to the potassium hydrate any remaining admixture of carbon dioxid. The oxygen in the measuring vessel O is forced toward the bell-jar R by a solution of calcium chlorid, coming from a basin pro- vided with large bottles (Ca C1 2 ). From R pass the tubes d and e, connected by rubber tubes with the communicating potash-bottles (K OH, k o h), which may be alternately raised and lowered by means of the scale-beam w. By these means the air is aspirated from R, and the carbon dioxid is absorbed by the solution of potassium hydrate. At the end of the experiment the increase in weight of the bottles represents the quantity of carbon dioxid expired. The amount of oxygen inspired is measured directly in the measuring vessel O. Finally, the manometer f shows whether there is a difference between the air-pressure within the jar and that on the outside. (c) The most complete apparatus is that of v. Pettenkofer (Fig. 88) . A cham- ber Z, made of metal and provided with a door and a window, has an opening for the entrance of air at a. A double suction-pump P P 1( driven by steam, renews COMPOSITION AND PROPERTIES OF ATMOSPHERIC AIR. 229 continuously the air in the chamber. This air is first conducted into the vessel b which is tilled W1 th pumice-stone saturated with water. Here the air becomes saturated with aqueous vapor, and then passes through the gasometer c, which indicates the total volume of the interchanged air; tht latter is then discharged into the outer atmosphere. The main tube x, leading from the chamber, carries a mercurial manometer q 9 r the detection of possible variations in pressure within the room This tube gives off a branch tube n, through which the air passes for chemical examination I he air in this tube is driven by a suction-apparatus M M 1? constructed on the principle of Muller s mercurial valve, and worked by the same steam-engineias .FiG. 88. Diagram of v. Pettenkofer's Respiration Apparatus. the pump P Pj. Before entering the pump the air passes through the sulphuric- acid bulbs, from whose increase in weight the amount of aqueous vapor can be estimated. After leaving the pump the air passes through the tube R, filled with baryta-water, which absorbs the carbon dioxid. The quantity of air passing through the branch tube n is then measured by the gasometer u, after which it finally passes into the atmosphere. The second branch tube N provides for^an examination of the air before entering the chamber, by an apparatus identical with that placed on the tube n. The excess of carbon dioxid and water found in n over that in N is due to the respiratory activity of the subject placed in the chamber. COMPOSITION AND PROPERTIES OF ATMOSPHERIC AIR. The dry atmosphere contains: Percentage in Percentage in Gas. Weight. Volume. 23.015 20.922 Including i per cent, in N 76.985 79- 02 volume of argon, together CO 2 0.029-0.034 with helion, and i part of krypton in 20,000 parts of air. The air contains likewise xenon, neon, coronium (lighter than hydrogen), and less than one-millionth part of aetherium (which latter possesses a specific 230 COMPOSITION AND PROPERTIES OF ATMOSPHERIC AIR. gravity only T o and the absorption of oxygen to V of the respective amounts during the waking state. Therefore, much less carbon dioxid is given off than there is oxygen absorbed, so that the body weight may even increase in consequence of the excess of oxygen taken up. 5. Influence of the Surrounding Temperature. The bodily tempera- ture of cold-blooded animals is easily raised by an increase in the sur- rounding temperature. Under such circumstances the animals give off more carbon dioxid than in a cooler state. For example, a frog exposed to a surrounding temperature of 39 C. excreted almost three times as much carbon dioxid as when the temperature was 6 C. Warm-blooded animals behave in a varying manner with changes in the surrounding temperature, accordingly as the bodily temperature remains constant, or is correspondingly raised or lowered. In the latter case, as in cold- blooded animals, a considerable decrease occurs in the excretion of carbon dioxid, when the body is cooled under the influence of cold surroundings. Conversely, elevation of the bodily temperature (also in the presence of fever) gives rise to increase in the excretion of carbon dioxid. The behavior is exactly the reverse when the bodily tempera- ture remains constant on exposure to varying surrounding temperature. With increasing cold of the surrounding medium, the consequent reflex stimulation causes an increase in the oxidation-processes of the body, as well as in the number and depth of the respirations. As a result, more oxygen is taken up and more carbon dioxid is given off. The involuntary muscular movement that occurs when the body is cooled has the most obvious influence on the increase in the gaseous inter- change. The season of the year also has an influence on the interchange of gases; in January a man consumed 32.2 grams of oxygen hourly, in July only 31.8 grams. In animals the carbon-dioxid excretion was found to be about one-third higher with a surrounding temperature below 8 C. than with a temperature above 38 C. When the tempera- ture of the air increases (without change in the bodily temperature), EXTENT OF THE RESPIRATORY EXCHANGE OF GASES. 235 the respiratory activity and the excretion of carbon dioxid diminish, while the pulse remains nearly constant. It has been shown that when there is a sudden change from cold to warm surroundings, the carbon- dioxid output diminishes considerably; and, conversely, when the change is from warm to cold, the excretion increases considerably. 6. Muscular Exertion produces a considerable increase in oxygen- consumption and carbon-dioxid elimination, which, for instance, may be three times as great in walking as in a quiet, recumbent position. Every kilogrammeter supplies 3^ milligrams of carbon dioxid; therefore, each additional gram of carbon dioxid formed is the equivalent of 300 kilogrammeters. The establishment of a certain degree of tension in the muscles requires more metabolic change than the maintenance of this tension. The increase in the interchange of oxygen and carbon dioxid begins almost immediately after the work commences. In a few minutes it attains a constant height of at most from seven to nine times the amount during rest. After the work is finished, the consumption of oxygen falls in from 3 to 15 minutes to the rate during rest. The respiratory quotient remains essentially unchanged during work. During light work there is relatively a little more oxygen consumed than during heavy labor. The production of carbon dioxid is diminished with practice, that is, with a more economically applied exertion of the muscles. The gaseous exchange is to a certain extent under the influence of the vagus nerve, which in part inhibits and in part accelerates the heart's activity. Irrita- tion of this nerve may produce a diminution in metabolism, characterized by a more pronounced fall in the absorption of oxygen than in the excretion of carbon dioxid; or it may call forth an increase in metabolism, distinguished by a greater rise in the output of carbon dioxid than in the oxygen taken in. 7. Ingestion of Food causes a not inconsiderable increase in the carbon-dioxid excretion, which is in general governed by the quan- tity of food. Hence, the increase is generally most pronounced (about 25 per cent.) from one-half to one hour after the chief meal (dinner). The increase in the consumption of oxygen that follows the intro- duction of food into the stomach depends in part upon the increased muscular activity of the alimentary canal; nevertheless, the increased exhalation of carbon dioxid cannot be attributed to this alone. It is also, and to a greater extent, dependent on the heat-producing activity of the digestive glands as in the case of the salivary glands. In addition, some of the carbon dioxid is derived from oxidation, in the course of urea-formation, of a part of the carbon contained in the proteids. The quality of the food also has some influence. According to Magnus-Levy a proteid diet causes a much greater increase in the con- sumption of oxygen (about from 70 to 90 per cent.) than does carbo- hydrate food (which increases the consumption about 39 per cent.), or a fat-diet (which causes an increase of only 15 per cent.), as experiments on dogs show. A fasting adult weighing 50 kilos inspires in one hour eight liters of air for each kilo; he consumes 0.45 gram of oxygen, and forms 0.5 gram of carbon dioxid. The ingestion of food raises these figures to nine liters of air, 0.5 gram of oxygen and 0.6 gram of carbon dioxid. The deposition of fat following a carbohydrate diet, is attended with an increase in the amount of carbon dioxid given off. results partly from combustion of the carbohydrates, and partly from their trans- formation into fat, during which process carbon dioxid is separated, tory quotient is also increased as a result of fat-formation following an abundant carbohydrate diet; the quotient under such conditions may even rise above 1.2. The absorption of oxygen is uninfluenced by direct injection into the 236 EXTENT OF THE RESPIRATORY EXCHANGE OF GASES. blood either of non-nitrogenous or of nitrogenous substances. The output of carbon dioxid changes to a certain extent in correspondence with the combustion of these substances by means of a constant quantity of oxygen. Hunger greatly reduces the combustive processes in dogs; but in guinea-pigs it produces at most a small reduction in the consumption of oxygen. 8. The Number and the Depth of the Respirations have practically no influence on the formation of carbon dioxid, or on the oxidation- processes in the body, the latter being regulated rather by the tissues themselves through a mechanism as yet unknown. These factors, however, have been observed to exert an evident influence on the removal of the carbon dioxid already formed in the body. An increase in the number of respirations, the depth remaining the same, as well as an increase in their depth, the number remaining the same, results in an absolute increase in the output of carbon dioxid. The quantity seems relatively diminished, however, when viewed with reference to the amount of gases interchanged. Example: NUMBER OF RESPIRATIONS IN EACH MINUTE EXCHANGED VOLUME OF AIR. CONTAINED C0 2 PER CENT. CO 2 . DEPTH OF RESPIRATION. CONTAINED C0 2 PER CENT. C0 2 . 12 6,000 258 cu.cm. = 4-3 P-C. 500 21 cu.cm = 4-3 P.C. 24 12,000 420 = 3-5 ' 1000 36 = 3-6 " 48 24,000 744 = 3- 1 1500 5i = 3-4 96 48,000 1392 = 2.9 ' 20OO 64 = 3- 2 3000 72 = 2 -4 Deep respirations, and also artificial respiratory movements, increase the absorption of oxygen into the blood to the point of saturation. Limitation of the supply of oxygen diminishes its consumption in the body in considerably greater measure than does hunger. Naturally, increased activity of the respiratory muscles causes in itself a greater interchange of gases. 9. Exposure to Light causes an increase in the excretion of carbon dioxid in frogs, mammals, and birds, even in frogs deprived of their lungs or of their cerebral hemispheres, or in those in which the spinal cord has been divided high up. At the same time the consumption of oxygen is increased. The same processes occur in individuals without eyes, though to a more limited extent. Rodents and birds show the maxi- mum in red light, toads in violet light. According to Aducco starving pigeons lose weight more quickly in the light than in the dark. Quincke demonstrated that certain tissues, such as leukocytes and parts of fresh tissues, attract more oxygen to themselves under the influence of light than in the dark. The nitrogenous metabolism of animals remains unchanged during exposure to light. The increased output of carbon dioxid is, therefore, to be attributed to an increased transformation of fat; hence, animals accumulate more fat when kept in the dark. 10. Blood-letting produces no diminution in the respiratory exchange of gases, but does cause an increase in the nitrogenous excretion. Pro- found anemic conditions diminish the interchange of gases. 11. Changes in the Atmospheric Pressure produce a slight diminu- tion in the interchange of gases if breathing is made easier; but if DIFFUSION OF GASES WITHIN THE RESPIRATORY ORGANS. 237 breathing is made more difficult, there is a slight increase. By inspira- tion of compressed air the absorption of oxygen is increased to an ex- ceedingly small extent. In order to give off one gram of carbon dioxid, a smaller amount of air is needed at a low atmospheric pressure than with a high barometer. There is no diminution in the excretion of carbon dioxid on high mountains. The effects of artificially rarefied air and of the rarefied atmosphere of high altitudes are not the same. A rare- faction of air to 450 mm. of mercury still has no effect, the metabolic changes proceeding unaltered. In the air of high altitudes metabolism is increased, and respiration becomes more frequent and deeper. Ac- cording to A. and J. Loewy and Zuntz the greater amount of light at high altitudes is the exciting factor. 12. In the presence of artificially induced dyspnea, as by tightly compressing the thorax, the proteid metabolism is increased the amount of urea being increased and there is an increase in the excretion of oxalic acid, acetone, ammonia, and sulphur in the urine. Pathological. According to the experiments of Grehant on {logs, it -appears that intense inflammation of the bronchial mucous membrane will diminish the output of carbon dioxid, even if there be fever. In cases of diabetes the body is able to take up the necessary amount of oxygen, but the quantity of carbon dioxid given off is diminished, and the respira- tory quotient is low. Among the poisons, thebain increases the output of carbon dioxid, while mor- phin, codein, narcein, narcotin, and papaverin diminish it. Curare lowers the metabolism enormously, the absorption of oxygen falling about 35.2 per cent., and the excretion of carbon dioxid about 37.4 per cent. Section of the spinal cord has a similar effect. DIFFUSION OF GASES WITHIN THE RESPIRATORY ORGANS. In the pulmonary alveoli the air is richest in carbon dioxid and poorest in oxygen. Further on, from the smallest bronchioles to the larger ones and then onward to the bronchi and the trachea, the respired air becomes, step by step, gradually more like the atmospheric air. Hence it is that if the expired air of a respiration be collected in two halves, the first half (coming from the larger air-passages) contains less carbon dioxid (3.7 volumes per cent.) than the second half (5.4 volumes per cent.). This inequality in the proportion of the gases at various levels of the respiratory organs necessarily causes a continuous diffusion of gases between the various levels, and also, finally, between the gases in the larynx and nasal cavities and the outside atmosphere. The carbon dioxid constantly diffuses from the depths of the air- vesicles toward the outer air, while the oxygen of the latter diffuses toward the gaseous mixture in the pulmonary alveoli. This diffusion is doubtless assisted materially by the constant shaking of the respiratory gases by the cardio-pneumatic movements. During hibernation, and also in cases of apparent death of long duration, this must be the only means for the exchange of gases within the lungs. Ordinarily, however, this mechanism is insufficient for the respiratory process; so that the ex- change of air produced by inspiration and expiration must be added to it. By this latter means atmospheric air is introduced into those parts of the lungs lying nearest to the large air-passages, from which and into which the diffusion-currents of oxygen and carbon dioxid pass more readily, on account of the greater differences in the tension of the gases. 238 INTERCHANGE OF GASES. If the inspired air contains a diminished quantity of oxygen, the necessary amount of oxygen can still be supplied to a certain extent by more rapid and deeper respirations. INTERCHANGE OF GASES BETWEEN THE BLOOD IN THE PUL- MONARY CAPILLARIES AND THE AIR IN THE ALVEOLI. This interchange of gases is accomplished almost exclusively by chemical processes, independently of the diffusion of gases. For the determination of the gaseous interchange it is first necessary to ascer- tain the tension of the oxygen and the carbon dioxid in the venous blood of the pulmonary capillaries. Pfluger and Wolffberg have accomplished this by cathe- terization of the lungs. An opening is made in the trachea of a dog, and an elastic catheter (Fig. 90, a) is introduced into the bronchus leading to the lower lobe of the left lung. In order to have the bronchus fit closely around the catheter, the latter is made to pierce a rubber sac inflated by means of a communicating rubber-ball pump c. In this way no air from that part of the lung can escape at the side of the catheter. The tube is at first closed at its outlet, and the dog is allowed to breathe independently and as quietly as possible. After four minutes the alveolar air in the closed-off part of the lungs is in complete equilibrium with the blood- gases. By means of a mercurial air-pump the air in the lungs is sucked out of the catheter (at 6) and analyzed. The tension of the carbon dioxid and the oxygen in this air will indicate in an indirect way the tension of these two gases in the venous blood of the pulmonary capillaries. For the direct estimation of the gases in various specimens of blood, these gases are removed by shaking the blood with another kind of gas. The composi- tion of the mixture will indicate the proportions in which the blood-gases have been mixed, and will thus serve to determine their tension. It is desirable to use as much blood as possible with a small quantity of gas; the amount of the latter should be about the same as that supposed to be present in the blood. In the following table are shown the tension and the percentage of oxygen and carbon dioxid in arterial and venous blood, as well as in the atmosphere and the air of the closed-off alveoli : I. V. Tension of O in arterial blood = Tension of O in the alveolar air of 29.6 mm. of mercury; increased by the catheterized lung = 27.44 mm. of warming; corresponding to a gaseous mercury; corresponding to 3.6 vol. per mixture containing 3.9 per cent, of O. cent. II. VI. Tension of CO 2 in arterial blood = Tension of CO 2 in the alveolar air 21 mm. of mercury; corresponding to of the catheterized lung = 27 mm. of 2.8 vol. per cent. mercury; corresponding to 3.56 vol. per cent. III. Tension of O in venous blood = 22 VII. mm. of mercury; corresponding to 2.9 Tension of O in the atmosphere = vol. per cent. 158 mm. of mercury; corresponding to 20. 8 vol. per cent. IV. Tension of CO 2 in venous blood = VIII. 41 mm. of mercury; corresponding to Tension of CO 2 in the atmosphere = 5.4 vol. per cent. 0.38 mm. of mercury; corresponding to from 0.03 to 0.05 vol. per cent. If the tension of the oxygen in the atmosphere (VII) be compared with that in venous blood (III) or in the alveoli (V) it will be seen that the absorption of oxygen into the blood during respiration can occur in the form of an equalization of tension. Likewise a comparison of the tension of the carbon dioxid in the atmosphere (VIII) with that in venous blood (IV) or with that in alveolar air (VI) might explain the INTERCHANGE OF GASES. 239 excretion of that gas in a similar manner. Nevertheless, the respiratory interchange of gases is a chemical process. According to v. Fleischl the concussion to which the venous blood is subjected on being pumped into the pulmonary arteries provides for a more ready escape of the carbon dioxid, a point that is of the greatest importance with respect to the respiratory process. The absorption of oxygen from the alveolar air for the purpose of oxidation of the venous blood in the pulmonary capillaries is a chemical process, as the gas-free hemoglobin in the lungs takes up oxygen to form oxy hemoglobin. That this absorption depends, not on diffusion of the gases, but on the atomic combination pertaining to the chemical process, is shown by the fact that the blood does not take up more oxygen when the pure gas is respired than when atmospheric air is respired; further, that animals that are made to breathe in a small, closed space will absorb into their blood all of the oxygen but traces, to the point of suffocation. If the respiratory absorption of oxygen were a diffusion-process, much more oxygen would have to be taken up in the first case in accordance with the partial pressure of the gas; while in the latter case such an extensive absorption could not take place. FIG. 90. Pulmonary Catheter. Even in highly rarefied air (high balloon-voyages) the absorption of oxygen remains independent of the partial pressure. However, in a space containing rarefied air a longer time and a more vigorous shaking are required for the absorption of oxygen by the blood at the tempera- ture of the body; that is, the absorption of oxygen is not diminished, but is retarded. In this way is explained the death, for example, of the aeronauts Sivel and Croce*-Spinelli, during an ascension to a height where the atmospheric pressure is only one-third the normal. The laws of diffusion come into play in connection with the absorption of oxygen only to the extent that the oxygen, in order to reach the red puscles, must, first of all, diffuse into the plasma, where it immediately ente: chemical combination with the erythrocytes. The excretion of carbon dioxid from the blood into the alveolar air could also be well represented in the form of an equalization of sion (diffusion) ; but here again chemical processes are operative al they have not yet been investigated in many details, of oxygen by the erythrocytes produces at the same time an expulsioi 240 RESPIRATORY GASEOUS EXCHANGE AS A DISSOCIATION PROCESS. of the carbon dioxid. This is proved by the fact that the whole of the carbon dioxid is more easily expelled from the blood if oxygen be at the same time introduced than if all gases are withdrawn. The result is different in the case of the serum, which when subjected to a vacuum will give up only a part of the carbon dioxid, while from 5 to 9 volumes per cent, are still retained ; the latter can be released only by the addition of acids. As this carbon dioxid, which exists in firm chemical combina- tion, also escapes on addition of erythrocytes, the corpuscles must contain a substance that acts like an acid in expelling the carbon dioxid. THE RESPIRATORY GASEOUS EXCHANGE AS A DISSOCIATION PROCESS. Some forms of gas enter into true chemical combination with other substances] when associated at a certain high degree of partial pressure of the gas in question. This chemical combination, however, is again dissolved as soon as the partial pressure diminishes and reaches a certain low level. Hence, by alternately raising and lowering the partial pres- sure, a chemical combination of the gas can be formed and again broken up. This process is called dissociation of gases. The minimal partial pressure is constant for the various substances and gases in question; but still the temperature, as in the case of the absorption of gases, has a marked influence ; namely, increase in temperature diminishes the partial pressure at which dissociation occurs. Calcium carbonate may be taken as an example to illustrate the dissociation of gases. When this substance is heated in the air to 440 C., carbon dioxid escapes from the chemical combination; but it is gradually taken up again by the calcium, after cooling has taken place. The chemical combinations containing carbon dioxid, and also those containing oxygen, namely, the oxy hemoglobin and the carbon-dioxid compounds, behave in a similar manner within the blood-stream; these also exhibit the process of dissociation. If these gaseous combinations are placed under conditions in which the partial pressure of these gases is exceedingly low (that is, when they are present in small amounts), the compounds are dissociated; that is, they give off carbon dioxid or oxygen, as the case may be, to the surrounding medium. If, however, they are now again brought into a medium in which, on account of an abundance of these gases, the partial pressure of the oxygen or the carbon dioxid is high, they are again taken up in chemical combination by these gases. The hemoglobin of the blood in the pulmonary capillaries finds a plentiful supply of oxygen in the alveoli; therefore, it combines with the oxygen, under the high partial pressure of that gas, forming the chemical compound oxy hemoglobin. On its way through the capil- laries of the greater circulation, the hemoglobin comes in contact with tissues poor in oxygen; the oxy hemoglobin is dissociated, its oxygen passes to the tissues, and the blood, with gas-free or reduced hemoglobin, returns to the right heart and thence to the lungs, in order to take up oxygen anew. The carbon dioxid meets the circulating blood in largest amount in the tissues. The high partial pressure of the gas in this situation causes the constituents of the blood to enter into chemical combination with the carbon dioxid. In the lungs, however, the partial pressure for carbon dioxid is low, the gas is dissociated, and it is excreted. It is CUTANEOUS RESPIRATION. 241 thus evident that, as concerns the blood, the giving up of oxygen and the absorption of carbon dioxid in the tissues, and, conversely, the absorption of oxygen and the giving up of carbon dioxid in the lungs, are processes that take place simultaneously. CUTANEOUS RESPIRATION. Method. If a human being or an animal is placed in the chamber of a respira- tion-apparatus (such as Scharling's or v. Pettenkofer's) , and the gases passing to and from the lungs are conducted through a respiratory tube, so that none of the gaseous interchange of the lungs enters the chamber, but only the transpiration of the skin, information can thus be obtained concerning the cutaneous respira- tion. The procedure of leaving the whole head of the subject outside the chamber, the neck being fixed air-tight in its wall, is less correct. The cutaneous respiration of a circumscribed part of the body for instance, of an extremity -may be studied by enclosing the part in an air-tight cylinder similar to that used for the arm in employing the plethysmograph. In twenty-four hours a healthy man loses through his skin which contains the respiratory organ in the moist sweat-glands, richly supplied with blood-vessels QT of his entire body- weight, which is greater than the loss through the lungs, since it bears a ratio to the latter of 3:2. Of this large loss of weight only from 8 to 10 grams are referable to the carbon dioxid given off. The remainder is comprised in the evaporation of water. Elevation of the surrounding temperature is attended with an increase in the amount of carbon dioxid given off. The excretion at between 29 and 33 C. amounts to 8 grams in twenty- four hours; above 33 C. it is 20 grams (sweating begins at this point); and at 38.4 C. the amount is 27.5 grams. Active muscular exercise likewise produces an increased excretion. Absorption of oxygen by the skin has also been demonstrated, the amount absorbed being either equal to the volume of carbon dioxid given off, or a little less. As the excretion of carbon dioxid by the skin is only about -^ of that by the lungs, and as the absorption of oxygen is only about T fo of that by the lungs, it is evident that the respiratory activity of the skin is in any event but slight. It is uncertain whether or not the skin gives off gaseous nitrogen or ammonia. According to Funke the skin secretes hourly 0.0824 gram of soluble nitrogen, this quantity being increased in the presence of renal disease. According to Rohrig, the excretion of carbon dioxid and of water exhibits certain daily variations. It is increased during digestion, after the application of cutaneous irritants, in the presence of obstruction to pulmonary respiration, of hyperemia of the skin, and when the blood contains an increased number of erythrocytes. In warm-blooded animals, with thick, dry epidermoid structures, the cuta- neous interchange of gases is still less than it is in man. In frogs and other am- phibia, with a constantly moist skin, cutaneous respiration becomes highly impor- tant. The skin here supplies from two-thirds to three-fourths of the total quantity of carbon dioxid excreted, and in hibernating frogs the proportion is still greater. The skin is, therefore,, a more important respiratory organ than the lungs. Im- mersion in oil will, consequently, kill these animals more readily than will hgatic the lungs. INTERNAL RESPIRATION OR TISSUE-RESPIRATION. The terms internal respiration and tissue-respiration are used to desig- nate the interchange of gases between the capillaries of the greater cir- 16 242 INTERNAL RESPIRATION OR TISSUE-RESPIRATION. dilation and the tissues. Those organic constituents of the tissues that contain carbon are subjected during their vital activity to a process of gradual oxidation, with the formation of carbon dioxid. Hence, the following inferences may be drawn : r. The chief seat for the absorption of oxygen and the formation of carbon dioxid is to be found within the tissues themselves. That the oxygen rapidly penetrates from the capillary blood into the tissues is shown by the fact that this blood rapidly becomes richer in carbon dioxid and poorer in oxygen, while oxygenated blood, kept warm out- side the body, changes much more slowly and incompletely. Further, if fresh pieces of tissue be placed in defibrinated blood rich in oxygen, the oxygen rapidly diminishes. Also, the circumstance that frogs de- prived of their blood exhibit almost as great an interchange of gases as do normal animals indicates that the gaseous interchange takes place in the tissues themselves. Moreover, if the chief seat of oxidation lay, not in the tissues themselves, but in the blood, then, if oxygen were withheld from the blood (during suffocation), those reducing substances that consume the oxygen in the process of oxidation should accumulate in the blood. This is not the case, for even the blood of suffocated animals contains only a trace of reducing substances. The absorption of oxygen into the tissues may occur in the form of a temporary storing of the gas, perhaps with the formation of intermediate lower oxida- tion-products. This is followed by a period of more rapid separation of carbon dioxid. Thus, the absorption of oxygen and the excretion of carbon dioxid in the tissues do not necessarily proceed on parallel lines and to the same extent. A clear picture of the development of carbon dioxid in the tissues is furnished by the fact that a larger amount of this gas is found in the cavities of the body and in their gases and fluids than in the blood of the capillaries. Pfliiger and Strassburg found the tension of the carbon dioxid (in millimeters of mercury) as follows : In arterial blood, 21.28 mm. In bile, 50.0 mm. " the peritoneal cavity, .... 58.8 ' hydrocele-fluid, 46.5 " acid urine, 68.0 The abundance of carbon dioxid in these fluids, as compared with that in the blood, can arise only from the addition to them of the carbon dioxid generated in the tissues. In the lymph of the thoracic duct the tension of the carbon dioxid (from 33.4 to 37.2 mm. of mercury) is, indeed, greater than in the arterial blood, but it is still considerably less than in the venous blood. This fact does not, however, justify the conclusion that only a small quantity of carbon dioxid is formed in the tissues from which the lymph is collected. It rather permits the inference, either that the lymph possesses less attraction for the carbon dioxid formed in the tissues than does the capillary blood, where chemical forces are active in the production at least of a partial combination of the gas; or that in the course of the slow lymph-current the carbon dioxid is partially given back to the tissues by equaliza- tion of tension; or, finally, that carbon dioxid is formed independently in the blood. Furthermore, it is to be pointed out that those muscles that are known to be the principal producers of carbon dioxid furnish this gas abundantly to the blood, their tissues being relatively poor in lymph- vessels. The amount of uncombined, free carbon dioxid, capable of being pumped out, in the fluids and gases mentioned indicates that the carbon dioxid passes over from the tissues into the blood in an uncombined free state. However, Preyer believes that the gas is carried over into the blood of the veins also in chemical combination. The interchange of oxygen and carbon dioxid varies considerably in the differ- ent tissues. In the first rank belong the muscles, which in a state of activity INTERNAL RESPIRATION OR TISSUE-RESPIRATION'. 243 excrete a large amount of carbon dioxid and consume much oxygen. The inter- change of gases in tissues is increased during their activity. The secreting salivary glands, kidneys, and pancreas are no exception to this rule; for although, in the secreting state, bright red blood flows away from them through the dilated vessels, still this apparently relative diminution in the carbon dioxid of the venous blood is more than compensated for by its absolute increase through the marked increase in volume of the blood passing through these organs. Active reduction-processes take place in most tissues. If coloring-matters, such as alizarin-blue, indophenol-blue, or methylene-blue, be introduced into the blood of animals, the tissues will soon be stained. Those organs that have an especially strong affinity for oxygen (such as the liver, the cortex of the kidneys, and the lungs), abstract oxygen from these coloring-matters, and change them into colorless reduction-products. The pancreas and the submaxillary gland have almost no reducing power. 2. The blood itself, like all of the tissues, is a seat for the consumption of oxygen and the formation of carbon dioxid. This is proved by the fact that blood removed from the body quickly becomes poorer in oxygen and richer in carbon dioxid; further, by the circumstance that in the oxygen-free blood of asphyxiated persons and in the blood-corpuscles there are always found small quantities of reducing agents, which become oxidized on the addition of oxygen. At all events, this gaseous inter- change is but slight as compared with that occurring in all the other tissues. It is incontestable that the walls of the blood-vessels, by means of their contained muscular fibers, also consume oxygen and produce carbon dioxid, although this process is so insignificant that the blood undergoes no visible change in color throughout its arterial course. C. Ludwig and his pupils have proved by specially adapted experiments that transformation into carbon dioxid can actually occur within the blood. If sodium lactate, which is easily oxidized, be mixed with blood, and this mixture be sent through the blood-vessels of a recently excised organ that is still alive (such as the kidney or the lung) , a more abundant consumption of oxygen and formation of carbon dioxid will occur in this mixed blood than would occur in pure blood similarly transfused. 3. It may in advance be concluded as probable that the living pulmonary tissue also consumes oxygen and generates carbon dioxid. By passing arterial blood through lungs that have been deprived of air, C. Ludwig and Miiller succeeded in demonstrating a diminution in the oxygen and an increase in the carbon dioxid. Bohr and Henriques con- cluded further from their experiments, in which they restricted to a considerable degree the circulation of blood through the bodily tissues, and found no significant diminution in the excretion of carbon dioxid from the lungs, that the pulmonary tissue is not limited to a mere excretion and absorption of gases, but that it besides possesses the prop- erty of forming carbon dioxid from substances that are derived from the other tissues. In like manner they assumed that oxygen is actively taken up by the lungs; that is, the lungs secrete carbon dioxid and absorb oxygen like a secreting gland. As the total amount of carbon dioxid and oxygen in the whole volume of blood at any one time is only about 4 grams, while the amount of carbon dioxid excreted daily is 900 grams, and the amount of oxygen absorbed is 774 grams, it is evident that the interchange of gases pro- ceeds with great rapidity, that the absorbed oxygen must be consumed and the carbon dioxid formed must be excreted quickly. As a result of an increased introduction of acids into the body there is a diminution in the consumption of oxygen (and in the production of heat), which in a high degree may give rise to an internal asphyxia of the tissues. 244 RESPIRATION IN A CLOSED SPACE. RESPIRATION IN A CLOSED SPACE, OR WITH ARTIFICIAL CHANGES IN THE AMOUNTS OF OXYGEN AND CARBON DIOXID IN THE RESPIRED AIR. Respiration in a closed space results in (i) a gradual diminution of the oxygen, (2) a simultaneous increase of the carbon dioxid, and (3) a diminution in the volume of gas. If the space is only of moderate size, the animal consumes the oxygen almost completely, the blood becomes almost free of oxygen, and death finally results, accompanied by asphyxial convulsions. The absorption of oxygen occurs, therefore, through chemical combination, independently of the laws of absorption. In larger closed spaces considerable accumulation of carbon dioxid takes place before the oxygen is diminished to such an extent that life is threatened. As the carbon dioxid can be excreted from the body only when its tension is greater in the blood than in the surrounding air, there will be retention of the gas as the amount expired into the enclosed space increases; and, finally, a return of the carbon dioxid into the body may take place. This occurs while the oxygen is still sufficient to support life. Death results, therefore, directly from poisoning by carbon dioxid, with the symptoms of dyspnea of short duration, to which are added stupor and subnormal temperature. This manner of death has been ob- served in rabbits, after they had reabsorbed some of the carbon dioxid that had been excreted previously by them. In pure oxygen, or in an atmosphere rich in oxygen, animals breathe in a per- fectly normal manner. A little more oxygen is absorbed, but still the amount of carbon dioxid excreted is not increased. In closed spaces filled with oxygen, animals finally die through the reabsorption of their excreted carbon dioxid. Rabbits have thus been observed to die after they had absorbed an amount of carbon dioxid equal to half the volume of their body, although the enclosed air still contained over 50 per cent, of oxygen. Human beings and animals can still breathe an air-mixture containing only 9 per cent, of oxygen; deepened respirations set in at 10 per cent., and discomfort at 8 per cent. Animals breathe with difficulty and lose consciousness at 7 per cent.; pronounced dyspnea makes its appearance at 4.5 per cent., and quite rapid suffocation at 3 per cent. The air expired by man under normal conditions still contains between 14 and 18 per cent, of oxygen. Mammals placed in a gaseous mixture poor in oxygen consume slightly less oxygen. The metabolism of animals is unchanged by variations in the amount of oxygen in the respired air between the limits of 10.5 and 87 per cent. If the oxygen falls below 10.5 per cent., there is an increase in the excretion of nitrogen, carbon dioxid, lactic acid, and oxalic acid through the urine. If the amount of carbon dioxid in the inspired air be increased, the respiratory movements are increased, but the excretion of carbon dioxid and the absorption of oxygen are diminished. Inspiration is actively stimulated by a deficiency of oxygen, as well as by an excess of carbon dioxid. The dyspnea that is induced under the condition first stated is prolonged and severe, while under the second condition the respiratory activity soon diminishes. A deficiency of oxygen further causes a greater and more prolonged rise in the blood-pressure than does an excess of carbon dioxid. Finally, the consumption of oxygen by the body is less restricted by a diminution of the oxygen in the air than by an excess of carbon dioxid. Death from limitation in the supply of oxygen is preceded by violent irritative phenomena and convul- sions, which are absent in case of death from excess of carbon dioxid. Finally, in conjunction with poisoning by carbon dioxid, the excretion of this gas is greatly diminished. If animals be supplied with a gaseous mixture similar to the atmosphere, but in which the nitrogen is replaced by hydrogen, they breathe quite normally; the hydrogen of the mixture does not undergo any noteworthy change in volume. Increase or diminution in the amount of nitrogen in the air simply causes a greater or lesser absorption of the gas by the fluids of the body. Cl. Bernard found that if an animal be made to respire in a closed space, it became, up to a certain point, accustomed to the successive deterioration of the air. If he placed a bird under a glass bell-jar, it lived for several hours; but if, before its death, another bird were added from the fresh air, the latter imme- diately died in convulsions. RESPIRATION OF FOREIGN GASES. 245 It is remarkable that frogs, when placed in air free from oxygen, will for several hours give off just as much carbon dioxid as in air containing oxygen, and this without any obvious disturbances. Hence, the formation of carbon dioxid must be independent of the absorption of oxygen, and the carbon dioxid must be set free in the decomposition of other compounds. Finally, however, complete motor paralysis sets in, while the circulation for a time remains undisturbed. RESPIRATION OF FOREIGN GASES. No gas is able to support life without a sufficient admixture of oxygen. Hence, without oxygen, all other gases will quickly cause suffocation (in two or three minutes) , even though they be in themselves harmless and indifferent. Completely indifferent gases are represented by nitrogen, hydrogen, and marsh-gas (CH 4 ). The blood of an animal breathing any of these gases yields no oxygen to it. Poisonous Gases. (a) Those displacing oxygen: (i) Carbon mpnoxid (CO). (2) Hydrocyanic acid (CNH) displaces (?) oxygen from the hemoglobin, with which it forms a more stable compound, and it thus kills with great rapidity. Further, it prevents the forma- tion of ozone from the oxygen in the blood. Blood-corpuscles charged with hydro- cyanic acid lose the property of decomposing hydrogen dioxid into water and oxygen. (b) Narcotic gases: (i) Air containing o.i per cent, of carbon dioxid has been designated as "bad air"; still, the discomfort experienced in such an atmosphere (for example, in overcrowded rooms) arises rather from offensive exhalations of unknown character than from the carbon dioxid itself. Air containing i per cent, of carbon dioxid produces marked discomfort; with 10 per cent, life is endangered, and with a higher percentage death ensues, accompanied by symptoms of coma. (2) When nitrous oxid (N 2 O) is respired, mixed with one-fifth its volume of oxy- gen, it causes in from one and one-half to two minutes a short, evanescent, especially pleasurable state of intoxication (laughing-gas) , which is followed by an increased excretion of carbon dioxid. (3) Pure ozonized air produces similar effects; it also causes short, agreeable excitement, then drowsiness and rapidly transient sleep. (c} Reducing gases, (i) Hydrogen sulphid (H 2 S) rapidly deprives the erythro- cytes of all oxygen, forming sulphur and water by oxidation; death occurs quickly, even before the gas can effect any change in the hemoglobin, with the formation of sulphur-methemoglobin. In addition, hydrogen sulphid forms in the blood sodium sulphid from sodium carbonate, the new compound rapidly causing death. (2) Hydrogen phosphid, phosphin (PH 3 ), is oxidized in the blood to form phosphoric acid and water, with decomposition of the hemoglobin. (3) Hydrogen arsenid, arsin (AsH s ), and hydrogen antimonid, stibin (SbH 8 ), act like hydrogen phosphid, but in addition they allow the hemoglobin to pass out of the stroma, so that the excreta, as the urine, contain hemoglobin. (4) Cyanogen (C 2 N 2 ) withdraws oxygen and further decomposes the blood. Irrespirable gases cannot be inspired at all, as they cause reflex spasm of the glottis on entering the larynx. If introduced forcibly into the air-passages, they give rise to violent inflammatory processes, followed by other disturbances and death. Included in this class are hydrochloric acid (HC1) , hydrofluoric acid (HF1), sulphurous acid (SO 2 ), nitrous acid (N 2 O 4 ), nitric acid (N,O 5 ). ammonia (NH 3 ), chlorin, fluorin, iodin, bromin, undiluted ozone, and pure carbon dioxid. OTHER INJURIOUS SUBSTANCES IN THE INSPIRED AIR. Particles of dust are among the impurities of the atmosphere that are harmful in large quantities and after long-continued action. Most of these particles are expelled externally by means of the ciliated epithelium of the respiratory organs, whose cilia wave toward the larynx. Some of the dust-particles, however, pene- trate the epithelium of the air- vesicles, and thus reach the interstitial pulmonary tissue, from which they frequently pass through the lymph- vessels to the lymphatic glands of the lungs. For this reason coal-dust is found deposited in the lun, of all elderly persons, blackening the alveoli. In moderate amounts stances are harmless in the tissues; but if the deposits become large, they may cause pulmonary diseases that may finally lead to disintegration of the lungs. The particles penetrate between the alveolar epithelium into the i monary tissue, and then into the lymphatic vessels and glands. In many trades 246 RENEWAL OF THE AIR IN LIVING-ROOMS. the work must be done in a dusty atmosphere, and they are thus rendered detri- mental to health. Charcoal-burners, grinders, stone-cutters, file-cutters, weavers, spinners, tobacco-workers, sawyers, millers, bakers, and others suffer from various affections of the lungs, induced by the dust of their trades. During a year's work a workman in a horse-hair mill inhales 15 grams of dust, in a saw-mill 27 grams, in a woolen mill 30 grams, in a grinding mill 37.5 grams, in an iron-foundry 42 grams, in a snuff-factory 108 grams, in a cement-factory 336 grams. The ciliated epithelium is exceedingly sensitive to mechanical excitation. The coordinated, continuous movement of the cilia on a larger surface does not depend wholly upon an external (mechanical) conduction of the stimulus, but also upon an internal conduction (as in the nervous system). There is no doubt that with the inspired air the germs of infectious diseases are often taken into the respiratory organs, whence they gain entrance into the body. Thus, the diphtheria-bacillus becomes localized in the pharynx and the larynx, the glanders-bacillus in the nose, the germ of whooping-cough in the bronchi, the microbes of hay-fever and ozena in the nose, the influenza-bacillus in the air- Outer layer Intermediary forms Inner layer Squamous cells FIG. 91. Stratified Ciliated Cylindrical Epithelium of the Larynx (Horse) (after Toldt). passages, the pneumonia-bacilhis in the air- vesicles. The cause of tuberculosis, the bacillus tuberculosis, enters the air-filled pulmonary tissue with the dust of tuberculous sputa, and may spread from that focus through all of the tissues. In a similar manner leprosy arises from the bacillus lepras. The cause of malaria, the plasmodium malariae possessed of ameboid movement, reaches the blood partly through the respiratory organs, changes the hemoglobin within the red corpuscles into melanin, and causes their destruction. In the same way the blood is invaded by the exciting agents of smallpox (micrococcus vaccinas), the spirillum of relapsing fever, the still little known microbe of measles, and the as yet undiscovered germ of scarlet fever, etc. Many disease-germs enter the mouth with the air, others with the food, and are swallowed, so that they undergo development in the intestinal tract. This is true of cholera (comma-bacillus), dysentery, typhoid fever (bacillus typhosus), and amebic enteritis (amceba coli; the amceba coli mitis is less virulent, and the amceba intestina vulgaris is harmless). In cattle, anthrax arises in the same way from bacterium anthracis. RENEWAL OF THE AIR IN LIVING-ROOMS (VENTILATION). EXAMINATION OF THE AIR. Fresh air is one of the most necessary conditions for salutary existence on the part both of the healthy and of the sick. It may be assumed that a sufficient renewal of the air in living-rooms will be assured, if 800 cu. ft. of space be allowed for every inmate of a room, and about 1000 cu. ft. for every sick person. The neces- sary space for the inmates of dwellings, schools, barracks, penal institutions, and hospital-wards should be measured accordingly, and the allotment of space to the individuals should be made only in this proportion. However, this standard has been materially departed from in various countries. In overcrowded spaces the amount of carbon dioxid at first increases. The normal amount in the air (0.5 in 1000) has been found increased in comfortable living-rooms to from 0.54 to 0.7 in 1000; in badly ventilated sick-rooms to 2.4 in 1000; in overcrowded auditoriums to 3.2 in 1000; in pits to 4.9 in 1000; in school-rooms to 7.2 in 1000. Although it is not the amount of carbon dioxid RENEWAL OF THE AIR IN LIVING-ROOMS. 247 that makes the air of crowded spaces injurious, but rather the exhalations from the outer and inner surfaces of the body, which at the same time render the air offensive to the sense of smell, still the amount of carbon dioxid is an indication of the degree of vitiation of the atmosphere. To determine whether or not the ventilation is sufficient in spaces crowded with individuals, the carbon dioxid of the air should be estimated quantitatively at the time of occupation; hence, in school-rooms, if possible, shortly before the close of the school-session , or in sick- wards or dormitories (barracks) shortly before daybreak. As a good, comfortable room-atmosphere contains less than 0.7 of carbon dioxid in 1000, the ventilation of a space must be considered insufficient if more than i.o in 1000 is found. The atmosphere contains only 0.0005 cubic meter of carbon dioxid in i cubic meter of air, and an adult produces hourly 0.0226 cubic meter of carbon dioxid. Therefore, it will be found on calculation that ventilation must supply 113 cubic meters (for a child 60 cubic meters) of fresh air hourly for each person if the carbon dioxid in the living-room is to be kept below 0.7 in 1000 0.7 : 1000 = (0.0226 -f x X 0.0005) : x ' hence, x = 113. If the amount of carbon dioxid in the air of a room be allowed to reach i.o in 1000, then an hourly ventilation of 45 cubic meters is sufficient for an adult, and 24 cubic meters for a child. The following method is employed to determine whether a living-room has sufficient ventilation. A large quantity of carbon dioxid is generated in the room, as much as i or 2 liters hourly for every cubic meter of space. The burning of stearin-candles may be employed as the source of carbon dioxid, each candle producing 12 liters of gas in one hour; a gas-burner supplies 100 liters an hour; an adult man produces 22.6 liters by respiration, and a school-child 12 liters hourly. If sufficient carbon dioxid has been produced at the end of an hour, the generator is removed, and the first estimation of carbon dioxid in the air is made, according to the method described later on. At the end of another hour, during which the windows and doors are kept closed, the second estimation of carbon dioxid is made. The amount of fresh air that has entered by ventilation during this hour is calculated by the following formula: C = 2.3 X m X log. - --*, in which C represents the volume in cubic meters of fresh air that has entered by ventilation in one hour, m the volume of room-space in cubic meters, p the amount of carbon dioxid contained in i cubic meter of the air in the room at the first estimation, expressed in cubic meters, q the amount of carbon dioxid in each cubic meter, found at the second estimation and expressed in cubic meters, a the carbon dioxid in atmospheric air = 0.0005 cubic meter in i cubic meter of air. Example: In a school-room, containing 40 children, the first estimation of car- bon dioxid is made shortly before the close of school. If the result be 2 in 1000, it will indicate the presence of 0.002 carbon dioxid in i cubic meter of air. After the children have gone, the windows and doors are again closed, and the second analogous estimation is made at the end of an hour. If the result be i in 1000, there will be o.ooi carbon dioxid in i cubic meter of air. The size of the school- room is 600 cubic meters. The quantity of fresh air that has entered the space during the hour can be estimated according to the foregoing formula: C = 2-3X 600 X log. 0.002-0.0005 = I3 8oX log. ^^ = 1380 X log. 3 - 1380 X o.ooi 0.0005 0.0005 0.4771213 = 658.3 cubic meters. Hence, 658.4 cubic meters of fresh air have entered the school-room by ventilation. As one child requires 60 cubic meters of fresh air hourly, the 40 pupils require 40 X 60 = 2400 cubic meters of fresh air in one hour; but, as a matter of fact, the ventilation of this space amounts to only 658.4 cubic meters; therefore, 1741.6 cubic meters are still wanting. Hence, either a better ventilation must be provided, or fewer children should be allowed to attend the school. A ventilation that amounts to more than three times the room-space hourly will be found to give rise to an unpleasant draft, and is, there- fore, often directly harmful in winter. For the school-room in question containing 600 cubic meters of space, only 1800 cubic meters of ventilation hourly would be permissible; hence, there is only space in that room for at most 30 pupils (30 >< 60 = 1800). As the space receives only 658 cubic meters of ventilation hourly, provision must be made by better ventilation for the addition of 1 142 cubic meters more of fresh air; but without further ventilation place could be found in the school for only u children (658 -r- 60). In ordinary living-rooms,' in which the necessary space (800 cu. f for every inmate, the air is sufficiently renewed by the numerous pores pos^ by the walls of the rooms, as well as by the going in and out, and further, in win- 248 RENEWAL OF THE AIR IN LIVING-ROOMS. ter, by stoves (a well-heated stove providing a ventilation of from 40 to 90 cubic meters of air hourly). That this ventilation is sufficient is proved by the fact that the amount of carbon dioxid in the room remains constant. When there is a more considerable difference between the temperature in the room and that outside (as in winter) , the ventilation is more than sufficient. If, however, the cubic space allotted to each inmate is too small, as in over- crowded hospitals, narrow ship-quarters, etc., then the necessary change of air must be provided for by means of contrivances for artificial ventilation. The same must be done if noxious exhalations are given off by the sick. Above all, however, it is to be noted that the natural ventilation through the pores of walls is greatly limited if they be damp. At the same time, damp walls are prejudicial to health by reason of their greater conduction of heat, and also because the germs of infectious diseases can develop in them, as in moist ground generally. Ventilation may be accomplished either by aspiration, the exchange of air being brought about by suction-power; or by pulsion, the fresh air being pumped into the room. The carbon dioxid contained in the air of a living-room may be estimated as follows: A baryta-solution is prepared, containing 10 grams of crystallized barium hydrate and 0.5 gram of barium chlorid in i liter of water. A large, dry, accurately graduated, 6-liter flask is filled with air from the room to be in- vestigated, by blowing the air for some time down to the bottom of the flask by means of a bellows. Then, by means of a pipet 100 cu. cm. of the baryta-solution are allowed to run into the flask, naturally displacing 100 cu. cm. of the air. The flask is then closed with a rubber cap, and is allowed to stand for two hours, being shaken occasionally. In this way all the carbon dioxid is absorbed by the baryta-solution. Then, 25 cu. cm. of the clear, supernatant fluid are withdrawn into a medicine-bottle, and are titrated with a normal oxalic-acid solution from a graduated buret, until a drop of the mixture, when placed upon turmeric paper, does not form a brown stain, that is until the reaction is neutral. A few drops of a' solution of 0.2 gram of rosolic acid in 100 cu. cm. of dilute alcohol may also be added to the baryta-solution in the medicine-bottle, producing a red coloration. When oxalic acid is added, the mixture is decolorized by the slightest excess of this acid. To prepare the normal oxalic-acid solution, 2.8636 grams of pure, crystallized, undecomposed oxalic acid, dried by having stood over concentrated sulphuric acid under a glass bell- jar for four hours, are dissolved in i liter of water; i cu. cm. of this solution is equivalent to i mgm. of carbon dioxid. The number of cubic centimeters of acid-solution added to the baryta-solution is noted. Now, 25 cu. cm. of the original baryta-solution, with which nothing has been done, are titrated in like manner with the normal acid-solution to the point of neutralization; here also the amount of the acid-solution added is noted. By subtraction the difference is found between the amounts of normal acid-solution added in both titrations. Each cubic centimeter of this difference is equivalent to i mgm. of carbon dioxid, and the resulting value must be multiplied by 4, in view of the fact that only 25 cu. cm. of the 100 cu. cm. of baryta-solution were titrated. The result gives the milligrams of carbon dioxid in six liters minus 100 cu. cm. of air. The milligrams of carbon dioxid thus determined are converted into cubic centimeters by multiplying them by 0.508 (as 0.508 cu. cm. of carbon dioxid, at o C. and 760 mm. of barometric pressure, weighs i mgm.). The volume of the air is further reduced to o C. and 760 mm. of barometric pressure. This is done according to the formula V, = v - B , in which V, represents the re- 760. (i + 0.003665.0 ' duced volume desired, V the volume of air taken in the flask for the experi- ment, B the barometer-reading taken at the time of the experiment, and t the temperature in the investigated room. By this reduction-procedure the results can be obtained in percentages for possible comparisons. Example: Twenty-five cu. cm. of the baryta-solution are neutralized by means of 24.6 cu. cm. of the oxalic-acid solution; 25 cu. cm. of the baryta-solution after the absorption of carbon dioxid (taken from the experiment-flask) are neutralized by means of only 21.5 cu. cm. of the oxalic-acid solution. The difference between them, 24.6 21.5 =3.1, represents 3.1 mgm. of carbon dioxid, which have been absorbed in the 25 cu. cm. of baryta-solution. Accordingly, there are contained in the 100 cu. cm. of baryta-solution employed 12.4 mgm. of carbon dioxid (4 X 3-i). If it be assumed that the large flask of air contains 4100 cu. cm., of which 100 cu. cm. have been displaced by an equal volume of baryta-solution that has been run in, so that there remains a volume of air equal to 4000 cu. cm.; NORMAL FORMATION OF MUCUS IN THE AIR-PASSAGES. 249 and if, at the time of the experiment, the temperature of the living-room was 20 C., and the barometer-reading 750 mm., then the reduced volume of air corre- sponding to the 4000 cu. cm. is V l = __^^J^_>^ = 3678 cu. cm., in which are contained 12.4 mgm. carbon dioxid. One mgm. of carbon dioxid, how- ever, equals 0.508 cu. cm.; hence, there were in 3678 cu. cm. of air 6.299 cu. cm. of carbon dioxid (12.4 X 0.508). In 1000 cu. cm. air this amounts to 1.7 cu. cm. (according to the formula x : 1000 = 6.299 : 3678), or 1.7 of carbon dioxid in 1000. NORMAL SECRETION OF MUCUS IN THE AIR-PASSAGES. THE EXPECTORATION (SPUTUM). The mucous membrane of the respiratory tract is covered by a thin layer of mucus. This mechanically hinders further formation of mucus by preventing the usual irritation of the air and dust. Additional mucus is secreted only in so far as it is rendered necessary to replace that lost by evaporation. As a rule, increased circulation of blood in the tracheal mucous membrane is attended with increased secretion. Division of the nerves on one side (in the cat) gives rise to redness on the same side, with increased secretion. On "catching cold" (for instance, as a result of covering the abdomen with ice) the mucous membrane first becomes completely pale, and then deep red, with marked increase in the secretion. Injection of sodium carbonate and ammo- nium chlorid restricts the secretion. The local application of alum, silver nitrate, or tannic acid dries the mucous membrane, so that the epithelium is cast off. Apomorphin, emetin, and pilocarpin actively stimulate the secretion; atropin and morphin limit it. Even under normal conditions hawking and coughing will cause the expectoration of slimy, viscid material, which may be derived from the entire respiratory tract, and is always mixed with a little saliva. In the presence of catarrhal conditions or of more serious disease the expectoration becomes more profuse, and is often mixed with charac- teristic products. It contains: 1. Epithelial cells, especially squamous cells from the mouth and the throat (Fig. 92, 8), more rarely alveolar epithelium (2), still more rarely ciliated epithelium (7) from the larger air-passages. Not rarely changes are found in the epithelium as a result of maceration, including the cylindrical cells that have already lost their cilia (6) and contain swollen nuclei. Alveolar epithelium (2), with a diameter from two to four times that of a leukocyte, is found especially in the morning-sputum, but only in that from per- sons over 30 years of age. In younger persons its presence indicates diseased conditions of the pulmonary parenchyma. Alveolar epithelium is found also in a state of fatty degeneration and filled with pigment-granules (3); also in the form of myelin-degenerated cells (4), that is, cells filled with clear refractive droplets of varying size, some being colorless, and some having absorbed pigment- granules (dust-particles). Also mucin in myelin-forms, that is, in the form of coagulated nerve-substance, is found constantly in the sputum (5). Mucus is stained yellow by safranin, while albumin is stained red. 2. Leukocytes (9) are present in large number in yellow sputum, and in smaller number in clear sputum. They are to be looked upon as white blood-corpuscles that have wandered from the blood-vessels. They also are often found in changed forms and in a state of dissolution ; they may be shrivelled up, filled with fat-granules, or they may appear as conglomerations of granules; and, finally, isolated nuclei indicate the destruction of their cell-body. 2 5 NORMAL FORMATION OF MUCUS IN THE AIR-PASSAGES. Eosinophile cells are found in the sputum from cases of asthma, and also in the nasal secretion from cases of acute coryza and of nasal polyps. Leukocytes containing hemosiderin are found after capillary hemorrhages in the air-passages. The fluid substance of the sputum contains much mucus, derived from the mucous glands and the goblet-cells, also some nuclein and lecithin, and the constituents of the saliva, according to the amount mixed with the sputum. Albumin is found in the sputum only in cases of inflammation of the air-passages; its amount increases with the degree of inflammation. Urea has been found in the sputum in cases of advanced nephritis. Pathological. In the presence of catarrhal conditions the sputum is usually at first glairy and slimy (sputa cruda) ; later, it becomes more consistent and yellow (sputa cocta) . FIG. 92. Objects Found in the Sputum: i, detritus and dust-particles; 2, pigmented alveolar epithelium; 3, fatty degenerated and partially pigmented alveolar epithelium; 4, alveolar epithelium showing myelin-de- generation; 5, free myelin-forms; 6, 7, desquamated ciliated epithelium, partly changed and deprived of its cilia; 8, squamous epithelium from the mouth; 9, leukocytes; 10, elastic fibers; n, fibrinous cast of a small bronchus; i 2 leptothrix buccalis, together with cocci bacilli, and spirochetae; a, fatty-acid crystals and free fatty granules; b, hematoidin; c, Charcot's crystals; d, cholesterin. Under pathological conditions there may be found in the sputa : (a) Erythrocytes, always from rupture of a blood-vessel. (6) Elastic fibers (10) from destroyed pulmonary alveoli. Usually they occur in small bundles of delicate fibers, which at times suggest the rounded walls of the alveoli by their curved arrangement. Naturally, they always indicate destruction of pulmonary tissue. (c) Much more rarely, in the presence of rapid and extensive disintegration of the lungs, there occur larger fragments of pulmonary debris, embracing several alveoli ; likewise small pieces of fibro-cartilage or unstriated muscle-fibers from the small air-passages. (d) Colorless coagula of fibrin (n) may be found, and are usually to be recog- nized as casts of the smaller or larger air-passages. They are formed in connection with inflammatory processes in the lungs or bronchi that are attended with a fibrinous exudation into the tubules. They are thus found frequently in cases of pneumonia in adults, in cases of bronchial croup, and also, rarely, in cases of severe influenza. EFFECTS OF ATMOSPHERIC PRESSURE. 251 (e) Crystals of various kinds : Fatty-acid crystals (a) , arranged in bundles of fine needles, usually lying in whitish, cheesy, fetid lumps of sputum. They indi- cate a more profound process of decomposition affecting the stagnating secretion and the underlying tissue. Crystals of leucin and tyrosin are rarely found as decomposition-products of the albuminates. Tyrosin is found more abundantly after rupture of an old abscess into the lungs. Colorless, octahedral or rhombic platelets with elongated points Charcot's crystals (c) have been found in the expectoration in cases of asthma, hang in and on peculiar, spirally wound plugs of exudate from the narrow air-passages; they have also been found in connection with other exudative affections of the bronchi. These structures, also called Curschmann's spirals, are produced when the respiratory air, in passing by, draws out parts of the secretion into threads, and rolls them spirally to and fro. Hema- toidin-crystals (6), from old effusions of blood in the lungs, occur rarely; likewise cholesterin-crystals (d) , arising from broken-up collections of pus. (/) Fungi and other low organisms are found in the sputum, being taken in during inspiration. The threads of leptothrix buccalis (12) occur frequently, having been detached from deposits on the teeth. Mycelial threads and spores are found in the sputum in cases of thrush, which occurs frequently in the mouths of nursing infants as white, spreading deposits (oidium albicans). Among the bacteria, the mucous-membrane streptococci (mostly diplococci) are constantly found, and frequently the micrococcus albus liquefaciens and harmless saprophytes; pyogenic cocci usually occur only in cases of pulmonary tuberculosis. In the presence of gangrene of the lungs monads and cercomonads have been found, in cases of pneumonia at times the bacillus pneumonias of Friedlander, in cases of influenza the influenza-bacillus of Pfeiffer and Canon, in cases of whooping-cough a minute diplococcus (according to Czaplewski and Hensel a non-motile bacillus), in cases of mumps a bacterium similar to the gonococcus, in cases of measles the bacillus causing that disease, in cases of pulmonary tuberculosis without exception the tubercle-bacillus. Rarely the sarcina is found; this is encountered more fre- quently in the stomach in the presence of gastric catarrh, and also in the urine. With regard to its external appearance sputum may be described as mucous, muco-purulent, or purulent. When heated at 60 C. all sputa are reduced to a uniform degree of fluidity. The sputum may have an abnormal coloration. Thus, it may be red from blood-pigment; if it remains long in the lungs, the blood-pigment may run through a whole scale of colors (as in external, visible blood-tumors), and it may thus give the sputa a dark-red, bluish-brown, brownish-yellow, deep-yellow, yellowish-green, or grass-green color. The sputum is sometimes yellow in cases of jaundice. Colored dust, if accidentally inspired, may also color the expectoration. The odor of the sputa is usually stale, and more or less unpleasant. It be- comes ill-smelling when it has remained for some time in pathological cavities in the lungs; it is stinking in the presence of gangrene of the lungs. EFFECTS OF ATMOSPHERIC PRESSURE. At the normal pressure of the atmosphere, with the barometer regis- tering 760 mm. of mercury, a pressure is exerted on the entire surface of the body amounting to from 15,000 to 20,000 kilos, corresponding to the extent of surface 103 kilos to each square decimeter. This pressure acts on the body equally from all sides, and in those internal air-spaces as well which are in direct communication with the outer air either constantly as the respiratory tract, the sinuses of the frontal, superior maxillary, and ethmoid bones or only temporarily as the digestive tract and the tympanic cavity. If an air-filled space, for example the tympanic cavity, be closed off from the outer air for some time, a rarefaction of the gases in the space occurs, as a result of the consumption of oxygen and its replacement by a smaller volume of carbon dioxid. As the fluids of the body (blood, lymph, secretions, parenchymatous juices) are practically incompressible, their volume may be regarded as unchanged by the prevailing pressure, however, absorb gases from the atmosphere in accordance with the pre- 252 EFFECTS OF ATMOSPHERIC PRESSURE. vailing pressure that is, the partial pressure of the several gases and also with their temperature. The solid constituents of the body are composed of innumerable and minute elementary parts, such as cells and fibers, of which each presents only a microscopic extent of surface to the influence of the pressure. Hence, the prevailing atmospheric pressure for every cell can be estimated only at a few milligrams, a pressure under which even the most delicate histological structures develop with ease. As an example of the action of atmospheric pressure on larger masses, attention may be called to the fact that, as a result of the adhesion of the smooth, sticky, articular surfaces of the shoulder- joints and the hip-joints, the arm and the thigh are supported without the aid of muscular activity; so that, for example, the thigh is still held in^ the acetabulum after all of the soft parts around the neck of the femur, including the articular capsule, are divided. An ordinary increase in barometric pressure has an influence on the respiratory activity in that it stimulates slightly the respiratory movements, while a fall in barometric-pressure has the opposite effect. The absolute amount of carbon dioxid remains the same; but in connection with the lessened frequency of respiration attending a low barometer, the percentage is naturally somewhat increased. Marked diminution in the atmospheric pressure, such as occurs in ascending mountains or in balloon-voyages (the highest known ascension, without loss of con- sciousness having been made by Berson of Berlin, to a height of 9145 meters at a temperature of 47.7 C.), causes a series of characteristic phenomena: (i) As a result of great diminution in the pressure on surfaces in direct contact with the air, they undergo marked congestion. Hence, there occur redness and swelling of the skin and exposed mucous membranes, even to the extent of causing hemor- rhages from the more delicate parts, as the nose, the lungs, the gums; turgidity of the cutaneous veins, profuse sweating, marked secretion from the mucous mem- branes. The arteries become more empty; at one-half the atmospheric pressure the blood-pressure in the radial artery begins to fall. (2) Other direct effects of diminished pressure are a feeling of weight in the legs, as the atmospheric pres- sure alone is not sufficient to keep the head of the femur in the acetabulum ; bulg- ing of the tympanic membrane by the air in the tympanic cavity, until the differ- ence in tension is equalized through the Eustachian tube, and as a 'consequence pain in the ears and even impairment of hearing. (3) The diminution in the tension of oxygen in the surrounding air causes difficulty in breathing and oppres- sion of the chest, as a result of which the respirations become more rapid (also the pulse), deeper, and irregular. At an elevation of from 3000 to 4000 meters the respiration and pulse are increased one-fourth ; when the atmospheric pressure is reduced from one-third to one-half, the blood loses oxygen, and in consequence there is incomplete removal of the carbon dioxid from the blood and a considerable diminution in the oxidation-processes in the body. When the atmospheric pres- sure is one-half or less, the amount of carbon dioxid in the arterial blood is dimin- ished, and the amount of nitrogen decreases in proportion to the diminution in atmospheric pressure. Rabbits kept under a pressure of from 300 to 400 mm. of mercury die on the third day, and present widespread fatty degeneration, espe- cially of the heart. In men and in animals, residence in high, mountainous regions appears to increase in the course of a few days the amount of hemoglobin in the blood and the number of red corpuscles. This effect should be favorable for the absorption of oxygen. A noteworthy phenomenon is the appearance of numerous microcytes in the first few days. Dyspnea from various causes also has a similar effect in man. (4) In consequence of the diminution in the density of the air, the latter is not able to produce loud tones in the larynx through the vibrations of the vocal bands; hence, the voice appears faint and altered. (5) In consequence of the determination of blood to the external parts in contact with the air, the internal parts become relatively poor in blood ; hence result diminution in the secretion of urine, muscular weakness, digestive disturbances, dulness of the senses, fainting spells, all of which phenomena are intensified by the conditions mentioned in EFFECTS OF ATMOSPHERIC PRESSURE. 253 paragraph (3) . According to the observations made by Whimper on himself during the ascent ot the highest peak in the Andes, the body can, to a certain extent accustom itself with respect to these latter phenomena. At an elevation of from 7000 to 8000 meters loss of consciousness occurs at times; the aeronauts Croce- bpmelli and Sivel lost their lives at a height of 8600 meters, where the rarefied air contains only 72 per cent, of oxygen (the air-pressure being 241 mm of mer- cury). In dogs a marked fall in the blood-pressure occurred first at 200 mm of mercury, accompanied by a small, slow pulse. The inhabitants of high, mountainous regions are sometimes attacked by an illness (mountain-sickness), which consists essentially of symptoms similar to those described, especially anemia of the internal organs, and which is accompanied bv a diminution in the amount of hemoglobin in the blood. Alexander von Hum- boldt found remarkable roominess of the thorax in the inhabitants of the high Andes. This phenomenon has been attributed to a diminution in the carbon dioxid of the blood, which serves as a stimulant to the respiratory center At an elevation of from 6000 to 8000 feet above the sea, water contains only about one- third the amount of air absorbed; therefore fish cannot longer live in it. Animals can be subjected to a still greater rarefaction of the atmosphere under the receiver of an air-pump. Under such conditions birds die when the air-pressure is reduced to 120 mm. of mercury; mammals at 40 mm. of mercury. Frogs endure repeated evacuation, and as a result they become much distended by escaping gases and aqueous vapor; after the entrance of air, however, they col- lapse completely. Hoppe-Seyler ascribes the cause of death in warm-blooded animals to the development of gas in the blood, the bubbles obstructing the capil- laries. Landois has often been able to confirm this phenomenon, and as far back as 1879 he suggested that the development of gas-bubbles in the parenchymatous juices, especially of the nervous system, might act injuriously through mechanical laceration of the tissues. Sudden reduction of a previously high air-pressure may act in a similar manner. The free gas that forms in the blood is almost pure nitrogen. The presence of air in the arteries of the spinal cord produces anemic paralysis, and later local destruction of the nerve-elements. Redi and Wepfer, in 1685, were the first to observe death from blowing air into the veins, as a result of mechanical obstruction to the circulation. Local diminution of the air-pressure results in marked congestion and swelling of the tissues in the affected part ; this is shown in the simplest manner by cupping. Under the name of the ' ' cupping-boot ' ' Junod described an apparatus for the rare- faction of air, made to include a whole extremity; this apparatus rendered possible a reduction to one-third in the air-pressure surrounding the leg. By this means from 2 to 3 kilos of blood may be aspirated into the leg, thus producing a temporary withdrawal of blood from other parts of the body, without causing a permanent loss of blood to the body. The energetic application is exceedingly painful, and the after-effects persist for 48 hours. Marked increase of the atmospheric pressure is accompanied by phenomena that may for the most part be explained as the reverse of those described in the dis- cussion of diminution of the air-pressure. They have been observed many times, partly in so-called pneumatic cabinets, in which, for therapeutic purposes, the pressure is gradually increased to one and one-fifth, two and two-fifths atmos- pheres and more; partly in closed reservoirs used in construction under water, and out of which the water is forced by pumping air in. Under such conditions men work at times even under a pressure of four and one-half atmospheres. The fol- lowing phenomena are worthy of attention: (i) Pallor and dryness of the external surfaces, collapse of the cutaneous veins, reduction in perspiration and the secretions from mucous membranes, greater supply of blood to the abdominal organs. (2) Pressing inward of the tympanic membrane (until the Eustachian tube allows the compressed air in the tympanic cavity to escape, often with a noise) ; considerable pain in the ears and even impairment of hearing. (3) A feeling of lightness and freshness during respiration. The respirations become slower (from 2 to 4 in a minute), inspiration is made easier and shortened, expiration is lengthened, and the pause is distinct. The capacity of the lungs is increased, owing to freer move- ment of the diaphragm, in consequence of diminution in the gases contained in the intestine. G. v. Liebig has noted an increase in the absorption of oxygen; Panum found that with the same volumes of air interchanged, the excretion of carbon dioxid is increased; the venous blood appears to be reddened. (4) Diffi- culty in speaking, a nasal metallic tone to the voice, inability to whistle. (5) In- creased secretion of urine; on account of the more rapid oxidation in the body, 254 COMPARATIVE. HISTORICAL. there is increased activity of metabolism, increase in muscular energy, increased appetite, subjective feeling of warmth. The pulse is slower, and the pulse-curve lower. On account of the invigorating and stimulating effect of a sojourn in moder- ately compressed air, the employment of the latter has been practised for thera- peutic purposes ; and it has been found that repeated applications have produced favorable after-effects of considerable duration. Unduly rapid increase of pressure is to be avoided and likewise unduly rapid removal of the pressure. Waldenburg and others have constructed apparatus in the form of a spirom- eter; either compressed air maybe inspired from its bell-jar, or the bell- jar may be filled with rarefied air, into which the expirations are made. Both methods are used in suitable cases for therapeutic purposes. Paul Bert has found at an excessively high, artificial atmospheric pressure, over 30 vol. per cent, oxygen in the arterial blood of animals (investigated at 700 mm. of mercury). If the amount of oxygen reaches 35 vol. per cent., death occurs, accompanied by convulsions. At a somewhat lower point the bodily tem- perature falls, the oxidation-processes in the body are reduced, strange to say, and as a result of this the formation of carbon dioxid and urea is diminished. Greatly compressed oxygen also produces the effect of a relative deficiency of oxygen; animals die in it, exhibiting signs of suffocation with greatly reduced metabolic processes. Frogs exhibit in compressed oxygen (up to 14 atmospheres) the same phe- nomena as they would in a vacuum or in pure nitrogen. There occurs paralysis of the central nervous system, at times preceded by convulsions. Then the heart stops beating (but not the lymph-hearts) , and at the same time the motor nerves lose their irritability; finally, the direct muscular irritability disappears. Under exceedingly high pressure of oxygen (thirteen atmospheres) an excised frog's heart beats scarcely one-fourth the time that it remains active in the air. If the quiet heart be brought into the air, the pulsations may return. Under a pressure of 100 atmospheres the frog's muscles still contract normally, and only at 400 atmospheres do they become paralyzed. Phosphorus ceases to be luminiferous under high pressure of oxygen, but not, however, the phosphorescent organisms, for example, the lamprey, or the phos- phorescent bacteria, such as those of meat (micrococcus Pflugeri). Exceedingly high atmospheric pressure is injurious to plants also. COMPARATIVE. HISTORICAL. Mammals have lungs similar to those of man. Those of birds exhibit a spongy structure; they are fused with the inner surface of the chest-wall, and have, on their outer surface, openings that lead into large, thin- walled air-sacs, lying among the viscera. These air-sacs further communicate with the cavities in the bones, which contain air instead of marrow, in order to provide greater lightness (pneu- maticity of the bones). There is no diaphragm. In reptiles the lungs are divided into larger and smaller divisions of vesicles; in snakes one lung atrophies, while the other becomes greatly drawn out and elongated, in accordance with the form of the body. Frogs pump air into their lungs by contraction of the pharyngeal sac, the nostrils being closed and the larynx opened. Turtles fill their lungs with air by a sucking movement. Amphibia (frog) possess two simple lungs, each of which in its structure to a certain extent represents an enormous infundibulum with its alveoli. When young (until their metamorphosis) they live as aquatic animals, and breathe by means of gills; the perennibranchiates (proteus) indeed, like the fishes, breathe in this manner throughout life. Among fishes the dipnoi, besides their gills, possess a swimming-bladder, abundantly supplied with afferent and efferent vessels, constituting an internal respiratory organ remotely comparable to the lungs. By the term "gills" is meant an organ for respiration in water, constructed in the form of numerous, vascular, plate-like diverticula. Among the fishes, the mud-fish (cobitis) exhibits an intestinal respiration, when there is lack of water and it buries itself in mud; in this process air is swallowed on the upper surface of the water, the oxygen is abstracted in the intestines, and carbon dioxid is discharged through the anus. Insects and centipedes respire through tracheas, which consist of numerous air-canals distributed throughout the body and com- municating with the atmosphere on the outer surface of the body by means of openings (stigmata) that can be closed. As insects possess no true circulatory movement of the blood, the air conducted through tubes penetrates from all sides COMPARATIVE. HISTORICAL. 2 55 into the blood-filled body-cavities; while in the lung-breathing vertebrates the blood conducted through tubes is brought from the whole body to the respiratory organ. The stigmata on the outer surface of the body, constituting the entrances to the tracheas, are provided with peculiar contrivances for closing, and can be employed for the emission of sounds. Arachnids respire by means of tracheas and lung-like air-sacs (tracheal pouches) ; crabs, by means of gills. Mussels and cephalo- pods possess fully developed gills; snails have partly gills, partly lungs. Among the lower animals, gill-like formations are still found among the round worms and in the echinoderms ; intestinal respiration occurs in the tunicates and many of the mites. Respiration by means of a water- vascular system, a system of canals through which water flows, is peculiar to the medusas and the flat worms. The lowest animal forms protozoa, sponges, polyps do not possess a special respiratory organ; in them the surfaces in contact with water carry on the respiratory interchange of gases. Historical. Aristotle (384 B. C.) regarded the object of respiration to be the cooling of the body, in order to moderate the internal heat. He observed cor- rectly that the warmest animals also respire most actively, but in the interpretation he reversed cause and effect; for the warm-blooded animals do not respire on account of their heat (for cooling purposes) , but they are warm as a result of their more active respiration (combustion). Galen (203-131 B. C.) already observed the purifying action of the respiratory organ, assuming that the "soot" was removed from the body with the expired air, together with the expired water. The most important experiments concerning the mechanics of respiration date from Galen. He maintained that the lungs passively follow the movements of the thorax, that the diaphragm is the most important respiratory muscle, that the external intercostals are inspiratory mus- cles, and the internal intercostals expiratory. He divided the intercostal nerves and muscles, and observed that loss of voice followed. After dividing the spinal cord at progressively higher levels, he found that successively higher thoracic muscles became paralyzed. Theophilus Philaretus taught that the circulation could be improved by loud crying, singing, or speaking. Oribasius (360 A. D.) observed that both lungs collapsed in the presence of double pneumothorax. Vesalius (1540) first described artificial respiration as a means of reanimating and stimulating the heart's action. Malpighi (1661) described the peculiar structures of the lungs. Lower (1669). saw the blood become bright red in the lungs. Borelli (died 1679) first explained most thoroughly the mechanism of the respira- tory movements. The chemical processes attending respiration were already suspected by Mayow (1679): "Ignis et vita iisdem particulis aereis sustinetur." However, more accurate knowledge could be obtained only after the discovery of the several gases coming under observation. J. B. van Helmont (died 1644) discovered car- bon dioxid, and found that the air was vitiated by respiration; but Black (1757) first discovered the excretion of carbon dioxid during respiration. In 1774 Pristley and Scheele discovered oxygen. Lavoisier, in 1775, found the nitrogen, and at the same time ascertained the composition of the atmosphere. The same investi- gator also represented the formation of carbon dioxid and water during respiration as being the result of combustion within the lungs. J. Ingenhousz (1779) dis- covered the respiration of plants the absorption of carbon dioxid and the giving off of oxygen during that process. Senebier (1785) found that this exhaled oxygen arose from decomposition of the carbon dioxid. Vogel and others definitely proved the existence of carbon dioxid in venous blood. Hoffmann and others demon- strated the presence of oxygen in arterial blood. Lavoisier with Seguin, in 1789, made the first communication concerning the quantitative absorption of oxygen and excretion of carbon dioxid during respiration. More complete insight into the interchange of gases during respiration could be obtained only after Magnus ex- tracted and analyzed the gases from arterial and venous blood. PHYSIOLOGY OF DIGESTION. THE MOUTH AND ITS GLANDS. The mucous membrane of the mouth contains sebaceous glands at the red edge of the lips. It consists of fibrillar connective tissue intermixed with fine elastic fibers. Toward the free surface it forms papillae, of which the largest (0.5 mm.) are found on the lips and the gums, including some with double points twin papillae. The smallest are on the palate and in the fold-like duplica- tures of the mucosa. The submucous tissue, which passes directly over into the mucosa, is thickest and most dense where the mucous membrane is immovably attached to the periosteum of the maxilla and the palate, and also in the vicinity of glandular involutions; while it is most delicate over movable and folded parts. The surface is lined by stratified nucleated squamous epithelium (Fig. 92, 8), and it is, as a rule, strongest and consists of the largest number of layers in regions where the papillae are longest. A diplosoma is found in the deeper cells of the surface of the tongue. All of the glands of the mouth, in- cluding the salivary glands, are divided, with reference to their secretion, into three groups: (i) albuminous or serous glands, whose secretion contains albumin; (2) mucous glands, whose ropy secretion contains mucin, together with some albu- min; (3) mixed glands, whose acini secrete partly albumin and partly mucin, as, for example, the submaxillary gland in man. For a description of their structure refer- ence may be made to page 258. Numerous mucous glands termed buccal, palatine, lingual or molar muciparous glands, in accordance with the region in which they occur are present in the tissue of the mucosa, their bodies appearing macroscopically as tiny white nodules. They represent the type of simple branched tubular glands. The con- tents of their secreting cells are partly mucus, which is expelled at the time of secretion. The excretory duct, formed of connective and elastic tissues, with a narrow outlet, is lined by a single layer of cylindrical epithelium. One duct often receives that of a neighboring gland. The labial glands are mixed glands. The small glands of the tongue deserve special consideration. Two morpho- logically and physiologically distinct glands can be distinguished, namely (i) mucous glands (E. H. Weber's glands), situated especially near the root of the tongue; compound alveolar glands, with bright, transparent, secreting cells and mural nuclei, and a rather thick membrana prbpria; and (2) serous glands (von Ebner's glands) , situated about the circumvallate papillae (and the foliate papillae in animals), and consisting of convoluted and branched tubules, characterized by small, narrow cells, filled with droplets of secretion, containing a centrosome and yielding an albuminous secretion. Halfwav up between the cells the intercellular secretory ducts are found. (3) The Blandin-Nuhn glands, within the tip of the tongue, consist of glandular lobules secreting mucus and saliva, and are, therefore, mixed glands. Delicate varicose nerve-fibers pass up to the cells. 256 FIG. 93. Section through Lymph-folli- cles of the Root of the Tongue (after Schenk): B, lymph-follicles; V, depression; A, adenoid connec- tive tissue; S, mucous glands; E, epithelium. THE SALIVARY GLANDS. 257 Of the blood-vessels, which are abundant, the larger lie in the submucosa, while the smaller penetrate into the papillae, in which they form either capillary networks or simple loops. Of the lymph-vessels the larger trunks, which form a coarse meshwork, lie in the submucosa, while the smaller, forming a finer network, pass through the mucous membrane itself. The cutaneous follicles or lymph-follicles constitute a part of the lymphatic apparatus. They form an almost coherent layer on the back of the tongue at its root. Several of these lymph-follicles always collect into a round mass, surrounded by connective tissue, and raising . the mucous membrane somewhat. In the center of every such collection is a depression (Fig. 93) into the bottom of which mucous glands empty and fill thesmall crater with mucous secretion. The tonsils exhibit on the whole the same formation, crypt-like depressions, into the sinuses of which small mucous glands empty, and surrounded by masses of from 10 to 20 lymph-follicles. Layers of firm connective tissue form a sheath about the tonsils. The pharyngeal and tubal tonsils exhibit a similar structure. Many medullated nerve-fibers, coming from the submucous tissue, ramify in the mucous membrane and terminate in part in separate papillas in the form of Krause's end-bulbs, in larger number on the lips and the soft palate, in smaller number on the cheeks and the floor of the mouth. Probably the nerves also spread out in the form of fine terminal nodules between the epithelial cells, accord- ing to the Cohnheim-Langerhans mode of distribution. Functionally these are sensory nerves and nerves of touch. THE SALIVARY GLANDS. The salivary glands and also the pancreas are compound tubular glands. The excretory ducts, formed of connective and elastic tissues (Wharton's duct contains also unstriated muscle-fibers) are lined with Fio. 94 .-Histolo g y of the Salivary GUu: J^J j ti^S^^^^ Into the structureless membrane of the acinus incorporated a layer V^ cells (Fig. 94, D). Next to the outer wall of the acinus 17 258 THE SALIVARY GLANDS. lymph-cavities, and beyond these the blood-capillaries run in a net-like meshwork. The lymph- vessels leave the gland at the hilum. The secreting cells are of varying structure, accordingly as the sali- vary gland secretes mucus (sublingual gland in man, submaxillary gland in the dog) or albumin (parotid gland in man), or is a mixed gland (submaxillary gland in human beings). Two kinds of cellular elements are found in the acini of the sub- maxillary gland of the dog and the sublingual gland of human beings: (i) The so-called mucous cells (Fig. 94, B, c), which bound the secretory cavity. They possess a membrane and are filled with a flattened nucleus turned toward the acinus- wall. Centrosomes are difficult to recognize. The cell-body is abundantly impregnated with mucin, which gives it a bright, highly refractive ap- pearance. On account of their mucous contents the cell-bodies hardly stain with carmine at all, while the nucleus takes up the stain. A process given off by the cell applies itself in a curved manner to the inner wall of the acinus. The true protoplasm of the cell is drawn out in a thread-like network from the nucleus through the mucin- mass. (2) The other variety of cellular elements form crescent-shaped complex bodies (Fig. 94, B, d) Gianuzzi's cres- cents, Heidenhain's composite marginal cells that lie in direct contact with the wall of the acinus. Each crescent con- sists of a number of small, closely packed, angular cells, with albuminous contents and nuclei and separated with difficulty. They are granular, darker, without mucous contents, easily impreg- nated by stains, and exhibit secreting spaces between the cells. The parotid gland (Fig. 95), secret- ing albumin in man and in mammals, contains but one kind of secretory cells, namely, cubical cells, with a coarse-meshed protoplasm, staining little with pigments, without a membrane, with serrated, readily stained, centrally situated, highly refractive nuclei, without nucleoli, with secre- tory ducts between them. The smaller cells of the salivary tubules bear a diplosoma near their free surface. The salivary glands of animals that secrete saliva free from mucus present similar features. By means of fine ducts, the so-called intercalary pieces, the terminal portions of the glands communicate with the thicker salivary tubules. The cells of these tubules, which, in their outer portions, appear fibrillated, and at times contain yellow granules (Fig. 94, E), bear a diplosoma near the surface. These salivary tubules empty into the excretory ducts. It is not improbable that these different portions of the gland also secrete different constituents of the saliva. FIG. 95. Diagrammatic Representation of a Salivary Gland: a, excretory duct; r, r, salivary tubules; s, intercalary portion; e, e, terminal portions. P, terminal por- tions of the parotid gland, with intercel- lular secretory ducts (stained black), passing over into the excretory duct (a) of the intercalary portion (s); r, parotid cell at rest; t, the same cell after secre- tion. THE SECRETORY ACTIVITY OF THE SALIVARY GLANDS. 259 THE SECRETORY ACTIVITY OF THE SALIVARY GLANDS. If the submaxillary gland of a dog is excited to active secretion by stimulation of its nerves, the mucous cells are after a while no longer seen but in their stead only smaller protoplasmic cells, devoid of mucus, within the acini. The mucous cells have discharged their mucus into the secre- tion of the gland, while their shrunken, dark-granular protoplasmic cell- bodies remain (Fig. 94, C). These are capable, after a certain period of rest, of producing new mucus. In regard to the crescents Stohr believes that they are produced mechanically by inequality in the secretory phases in adjacent acinus-cells. The cells reduced in size after having discharged their mucus are pressed to the wall by other cells filled with mucus and therefore much swollen, and thus the flattened composite marginal cells are formed. Recently R. Krause and others, differing from this state that the composite marginal cells secrete only serum and have no relation with the mucous cells. In the parotid gland of the rabbit, after secretion induced by stimula- tion of the sympathetic nerve, the gland-cells assume a more shrunken appearance, and their contents become more granular and more readily stained. The nuclei appear rounder and exhibit a nucleolus (Fig. 95). Ranvier observed in the secretion of the albuminous glands (submaxillary gland in the rat) that, after stimulation, many motile vacuoles were formed in the gland-cells. The water of the secretion is formed in the vacuoles, and in its excretion, carries with it the soluble ferment of the cells. A similar phenomenon occurs within mucous cells and also in goblet-cells. Morphological changes occur also in the cells of the salivary tubules. THE NERVES OF THE SALIVARY GLANDS. All the salivary glands derive their nerve-supply from two sources, namely from the sympathetic nerve and from a cranial nerve. The nerve-fibers, chiefly medullated, in part also non-medullated, pass in at the hilum and form a plexus rich in ganglion-cells between the lobules of the gland. The sympathetic nerve sends branches (a) to the submaxillary and sublingual glands, derived from the plexus surrounding the external maxillary artery (Fig. 243) ; (b) filaments pass to the parotid gland from the sympathetic plexus, which, piercing the parotid, surrounds the external carotid artery. Of the cranial nerves, (a) the submaxillary and sublingual glands are supplied by filaments from the chorda tympani branch of the facial nerve, (b) To the parotid gland fibers pass from the glosso-pharyngeal nerve in the dog, especially from its tympanic branch, which sends fibers through the tympanic plexus to the lesser superficial petrosal nerve. Together with the latter the former pass down- ward over the anterior surface of the petrous portion of the temporal bone, then through the sphenoidal fissure to the otic ganglion. With the latter they con- tinue through communicating branches to the auriculo-temporal nerve (from the third division of the trigeminal nerve) , which, covered by the parotid gland, on its way to the temple, sends the fibers to the gland. The submaxillary ganglion, which gives off fibers to the submaxillary and sublingual glands, derives its roots from the tympanico-lingual plexus, as well as from the sympathetic plexus about the external maxillary artery. With regard to the terminal distribution of the nerves to the salivary glands, two varieties are to be distinguished: (i) the vasomotor nerves, which give branches to the muscular walls of the blood-vessels, and (2) the true glandular nerves. According to Arnstein the latter form a surrounding network outside of the gland-tubules. From this plexus fine filaments pierce the membrana propria and terminate on the surface of the secreting cells with a peculiar end-apparatus: namely, branched twigs possessing tiny bulbs or mulberry-shaped masses. The same condition exists in the sebaceous, sudoriferous, and mammary glands and in the pancreas. 260 INFLUENCE OF NERVES ON THE SECRETION OF SALIVA. THE INFLUENCE OF THE NERVOUS SYSTEM ON THE SECRETION OF SALIVA. The Submaxillary Gland. Stimulation of the facial nerve at its root causes profuse secretion of limpid saliva deficient in the specific constituents. At the same time the blood-vessels of the gland undergo , dilatation. The capillaries, in the presence of increased blood-pressure in them, undergo such a degree of dilatation that the pulsating move- ment of the arteries is transmitted into the veins. More than four times as much blood flows back from the vein, which, besides, appears almost bright red in color and contains more than one-third as much oxygen as the venous blood of the unstimulated gland. In spite of the relatively large amount of oxygen in venous blood, the secreting gland consumes absolutely more oxygen than the inactive gland. The facial nerve contains two sets of functionally different fibers: (i) true secretory nerves and (2) vasodilatator nerves. It is not per- missible to regard the phenomenon of secretion as a simple result of increased circulatory activity. Stimulation of the sympathetic nerve causes the scanty secretion of a viscid, gelatinous, ropy saliva, containing the specific constituents, particularly mucus and the salivary corpuscles, in abundance, and having a specific gravity of from 1007 to 1010. At the same time, with de- crease in the blood-pressure, the blood-vessels of the gland undergo contraction, so that the small amount of blood escapes from the veins with a dark-blue color. The sympathetic nerve likewise contains two sets of functionally different nerve-fibers, (i) true secretory fibers and (2) vasoconstrictor nerves. Continued stimulation of the chorda tympani and the sympathetic nerve alters the secretions, making them more nearly alike, and thus teaches that, essentially, the saliva pro- duced by stimulation of the chorda tympani and that produced by stimulation of the sympathetic nerve differ not specifically, but only in degree. With increasing nerve-stimulation the secretion increases, and with it the amount of contained salts. The organic constituents depend, in addition to the intensity of the stimula- tion, upon the condition of the gland, whether at rest or exhausted. The constitution of the blood and the circulatory conditions in the gland likewise influence the composition of the saliva. That the secretion of the glands cannot be considered as a simple filtration as the result of changes in blood-pressure, but that it occurs as an independent function in conjunction with changes in the blood-vessels, will appear from the following considerations : 1. The secretory activity of the gland, on stimulation of the nerves, continues for some time even after all blood-vessels have been ligated. 2 . Atropin and daturin destroy the activity of the secreting fibers in the chorda tympani, but not that of the vasodilator fibers. 3. The pressure in the excretory ducts of the salivary glands, which can be measured by means of a manometer tied in the duct, may be almost twice as great as that in the arteries of the gland, having reached about 290 mm. of mercury in the excretory duct of the submaxillary gland. With increase in the pressure the amount of saliva diminishes, as does likewise the amount of work performed by the gland. 4. The salivary glands, in the same way as nerves and muscles, also fatigue, especially after injection of acids or alkalies into the excretory duct. This indi- cates that the secretory structure is independent of the circulation and under the influence of the nerves. 5. That in the secretion of saliva the cellular activity of the glands also is evident is shown by the researches of Zerner, who, after intravenous injection of indigo-carmine, found this substance within the mucous cells and the rod-cells. It must, therefore, be inferred that the nerves exert a direct influence on the INFLUENCE OF NERVES ON THE SECRETION OF SALIVA. 261 secreting cells of the glands, independent of any mediation on the part of the blood-vessels. As the direct anatomical connection between the nerve-fibers and the secreting cells appears proved, so, also, is the physiological connection to be accepted. During the process of secretion the temperature of the submaxillary gland rises about 1.5 C. The gland, as well as the venous blood leaving it, is not rarely warmer than the arterial blood. Between the irritation of the nerve and the beginning of secretion, from 1.2 to 24 seconds elapse. Paralytic Secretion of Saliva. By this term is understood the persistent secre- tion of limpid saliva from the submaxillary gland, which sets in twenty-four hours after division of the cerebral nerves, whether the sympathetic nerve is also injured or is preserved. It increases for perhaps eight days; then, with degeneration of the gland, it decreases. The injection of small amounts of curare into the artery of the gland also produces the condition, which is prevented by apnea, while dyspnea favors it. After a unilateral lesion both glands are said to take part in the secretion. According to Langley, after division of the chorda tympani, its central end acquires increased irritability. This exerts a centripetal effect upon the salivary center on both sides. At the same time, soon after the division, a ganglionic local secreting center, situated in the gland of the same side, also is stimulated, so that, if all of the nerve-fibers passing to the gland are!later'separated, the salivary secretion from the gland still continues. The Sublingual Gland. Probably the conditions existing here en- tirely resemble those found in the submaxillary gland. The Parotid Gland. Stimulation of the sympathetic nerve alone does not cause the secretion of saliva in the parotid in the dog. This occurs only when the branch from the glosso-pharyngeal nerve to the parotid, which is accessible in the tympanic plexus within the tympanic cavity, is also stimulated at the same time. Then a viscid saliva, rich in organic elements, is poured out. Stimulation of the cerebral branch alone produces a clear, watery saliva, with few organic constituents, but containing salivary salts. According to Langley, the sympathetic nerve also contains independent secre- tory fibers, which can be demonstrated only by stimulation soon after the termi- nation of the irritation of the tympanic nerve. After destruction of the tym- panic plexus, the parotid gland atrophies. Stimulation of the glosso-pharyngeal nerve in the rabbit causes secretion also in the glands of the tongue, with redness of the foliate papillae. In the intact body excitation of the nerves causing secretion of saliva occurs through reflex influences, a watery (cerebral) saliva being secreted under normal conditions. The nerve-fibers conveying the impulse cen- tripetally are: (i) the gustatory nerves; (2) the sensory fibers of the trigeminal and glosso-pharyngeal nerves of the entire buccal cavity. These seem also to cause the secretion of saliva by mechanical irritation through the movements of mastication. Pfliiger found that, on the side upon which mastication took place, one-third more saliva was secreted. Cl. Bernard observed the secretion to cease in horses while drinking. (3) The olfactory nerves, excited by certain exhalations. (4) The gastric branches of the pneumogastric nerve, especially in asso- ciation with strangling movements. (5) Even the irritation of distant sensory nerves, such as those of the conjunctiva, by the application of irritating fluids in carnivora. Further, stimulation of the central extremity of the divided sciatic nerve causes the secretion of saliva. In this category is probably to be included also the saliv tion sometimes observed in pregnant women. By irritation of distant nerves both centers are excited reflexly; when nearby nerves are irritated, the center on the same side is especially excited. 262 THE SALIVA FROM THE INDIVIDUAL GLANDS. The reflex center for the secretion of saliva is situated in the medulla oblongata, at the origin of the seventh and ninth cranial nerves. The center for the sympathetic fibers also is situated here. If the center is directly irritated mechanically, as by pricking, salivation occurs; suffocation has the same effect. This reflex may be inhibited by irrita- tion of certain sensory nerves, as by drawing forward loops of intestines. The reflex center is in direct communication with the cerebral hemi- spheres, as is evident from the fact that, with the thought of savory substances, especially during the state of hunger, watery salivation takes place. Irritation of the cerebral cortex, in the region of the cruciate sulcus (Fig. 258) also causes a flow of saliva in the dog. Also central disease in human beings may induce abnormalities in the secretion of saliva through their influence upon the intracranial center. As long as all nerve-irritation is suppressed, no secretion of saliva takes place, as, for instance, during sleep. Secretion likewise ceases immediately after division of all of the glandular nerves. Inflammations of the buccal cavity, neuralgia involving the nerves of the mouth, irruption of the teeth, ulcers of the mucous membrane, spongy conditions of the gums (as from the long-continued use of mercury) often induce active secretion of saliva (salivation, ptyalism), which rarely is unilateral. The parotid gland in the sheep (ruminant) secretes continually. Division of all of the afferent nerves does not affect this secretion. Perhaps this gland con- tains a center through which secretion is excited. Certain poisons also cause salivation by direct nerve-irritation, especially pilo- carpin. Some, particularly atropin, paralyze the cerebral salivary nerves, and thus cause a cessation of secretion. Administration of muscarin under these con- ditions causes resumption of the secretion. Pilocarpin acts by irritation of the chorda tympani. Administration of atropin during the resulting salivation causes this to cease. Conversely, in the condition of abolished secretion of saliva following the administration of atropin, pilocarpin or physostigmin causes a re- sumption of the secretion. Curare acts as a sialogog by irritation of the center. THE SALIVA FROM THE INDIVIDUAL GLANDS. Method. For obtaining the isolated saliva from the individual glands a thin metal tube is introduced into the excretory duct. If masticatory movements are then performed, or if a pungent substance be placed upon the tongue, the saliva will flow from the tube, drop by drop. Parotid saliva is not ropy, dropping readily, of alkaline reaction, with a specific gravity of from 1003 to 1006. It contains 6.84 per cent, of total solids, of which 3.40 per cent, are inorganic. On standing it be- comes cloudy and precipitates, together with some globulin, calcium carbonate, which is dissolved in fresh saliva as bicarbonate. Through the precipitation of calcium, salivary calculi may be formed in the excretory ducts; dental calculi likewise may form, enclosing leptothrix- threads and bacteria. Of the organic constituents of parotid saliva the most important is ptyalin; mucin is absent. Saliva contains, further, small amounts of a globulin-like body, alkali- albuminate and albumin, together with some urea, traces of volatile acid, and it appears never to be free from potas- sium or sodium sulphocyanid, which is wanting in some animals. This substance is recognized, after acidulating the saliva slightly with hydro- chloric acid, by adding a solution of ferric chlorid, when, with the formation of ferric sulphocyanid a dark red color results. Potassium sulphocyanid reduces THE MIXED SALIVA, THE SECRETION OF THE MOUTH. 263 hydriodic acid when added to saliva, with the development of a yellow color, and the formation of iodin, which can be recognized by the addition of starch. It is absent when the flow of bile into the intestine is prevented. It is formed through proteid metabolism, perhaps from the contained cyanogen. As potassium sulphocyanid is toxic for plants and microorganisms, it may be concluded that it acts, within certain limits, as a disinfectant for the buccal cavity. The inorganic elements in the saliva are mainly potassium and sodium chlorids, with calcium bicarbonate, and calcium and sodium sulphates, phosphates, and chlorates. The submaxillary saliva is alkaline, sometimes strongly alkaline. On standing for some time it precipitates fine crystals of calcium car- bonate, together with an amorphous, albuminoid substance. It always contains mucin, and it is, therefore, as a rule somewhat ropy; also ptyalin less than in the parotid secretion; and only 0.0037 P er cent, potassium sulphocyanid. In the submaxillary saliva of the dog there were found 1.755 of organic matter, of which 0.662 was mucin; from 2.604 to 3.662 of inorganic salts; and from 0.263 to 1.123 f soluble salts. Pfliiger investigated the gases of the submaxillary saliva and found, in 100 cu. cm. of saliva, 0.6 of oxygen, 64.7 of carbon dioxid, partly removable by exposure to a vacuum and in part capable of being expelled by phosphoric acid; and 0.8 of nitrogen; or of gases in 100 volumes 0.91 of oxygen, 97.88 of carbon dioxid, and i. 2 1 of nitrogen. Kiilz found in human parotid saliva as much as 1.46 volumes per cent, of oxygen and 3.2 of nitrogen, 4.7 of carbon dioxid removable by suction, and 62 of combined carbon dioxid. The sublingual saliva, more viscous and more coherent than the submaxillary saliva, is strongly alkaline in reaction. It contains much mucin, numerous salivary corpuscles and some potassium sulphocyanid; but its composition has, on the whole, not been determined accurately. THE MIXED SALIVA, THE SECRETION OF THE MOUTH. The buccal fluid is a mixture of the secretions of the salivary glands and the small glands of the mouth. Physical Properties. It is an opalescent, tasteless and odorless, somewhat ropy fluid, with a specific gravity of from 1002 to 1006, and an alkaline reaction, due to alkaline phosphates. Between midnight and morning the reaction may be faintly acid. The decom- position of epithelium, of salivary corpuscles or of remains of food by microbes may also cause the reaction to be acid temporarily, particularly after long fasting and after much talking. In the presence of digestive disturbances and of fever the reaction is not rarely acid, in consequence of stagnation and insufficient secretion; therefore, also, the mouth is dry. The amount in twenty-four hours is between 200 and 1500 grams, according to Bidder and Schmidt between 1000 and 2000 grams. The total solids in the secretion amount to 5.8 per cent. The solids are : 2.2 of epithelium and mucus, 1.4 of ptyalin and albumin, 2.2 of salts and 0.04 per cent, of potassium sulphocyanid in 1000. especially potassium, phosphoric acid and chlorin. Microscopical Constituents. (a) The salivary corpuscles, from 8 to n // m size, are nucleated, protoplasmic, spherical cells, without a limiting membrane exhibit as a vital phenomenon so-called molecular movements on the part of then numerous dark granules, which are embedded in the protoplasm, through whose internal flowing movement they are set into a tremulous, dancing locomotion, which ceases with the death of the cells. Salivary corpuscles can be easily brought into view by slight pressure upon the excretory ducts beneath the tongue. 264 PHYSIOLOGICAL ACTIONS OF THE SALIVA. (6) Desquamated squamous epithelium is never absent, and is present in abundance in association with catarrh of the buccal cavity (Fig. 92, 8). (c) Living organisms, which grow as saprophytes upon the buccal fluid and remains of food, at times in carious teeth, consist of the threads of the leptothrix buccalis (Fig. 92, 12), which turn blue, as a rule, on addition of iodin, and multiply with enormous rapidity. Leptothrix vegetations enter the dental tubules and cause caries of the teeth. The zooglea-form of the leptothrix appears as a cream- like, yellowish, smeary deposit on the teeth. Miller found in all healthy human beings, in addition to the ordinary leptothrix buccalis, another variety, the lepto- thrix buccalis maxima, also the iodococcus vaginatus, the bacillus buccalis maximus, the spirillum sputigenum and the spirochaeta dentium. Further, pathogenic bacteria may be present, as, for instance, those of pneumonia, of diphtheria, etc. Chemical Properties. (a) Organic constituents : a globulin-like albu- minous substance, mucin, ptyalin; fats and urea are present only in traces; about 130 mg. of potassium or sodium sulphocyanid in twenty- four hours. (b) Inorganic constituents: sodium chlorid, potassium chlorid, potas- sium sulphate, alkaline and earthy phosphates and ferric phosphate. According to Schonbein, saliva contains traces of nitrous salts, which are recog- nizable from the yellow color produced by metadiamidobenzol in saliva diluted five times with water after addition of a few drops of dilute sulphuric acid ; also traces of ammonia. Fresh saliva is said to contain hydrogen dioxid, which oxidizes the ammonia to nitrous acid; though when the reaction of the saliva is acid nitric acid is formed. Abnormal Constituents of the Saliva.. In cases of diabetes lactic acid has been found as a result of decomposition of the sugar. It dissolves the calcium of the teeth and may thus give rise to caries, as in cases of diabetes, v. Frerichs found leucin, and an increased amount of urea and albumin were observed in cases of nephritis, and uric acid in cases of uremia. Of foreign substances that are admin- istered there appear in the saliva mercury, potassium, metallic and free iodin and bromin, the last displacing an equivalent amount of chlorin from the salivary chlorids, lead, morphin, lithium, and sodium chlorid. Of the salivary glands in the new-born infant only the parotid contains ptyalin. In the submaxillary gland and in the pancreas the diastatic ferment appears to be formed not earlier than the end of the second month. Therefore the nourish- ment of infants with starches is not advisable. It is a remarkable fact that in new-born infants suffering from thrush (due to oidium albicans) no ptyalin is demonstrable in the saliva. For the infant that takes milk alone, the diastatic action of the saliva is not indispensably necessary. Therefore, the mucous mem- brane of the mouth appears to be but slightly moistened during the first two months, though an abundance of saliva is secreted later . Also, the glands usually attain a considerable size only after the first half-year of life. The irruption of the first teeth causes the secretion of much saliva in consequence of the irritation of the buccal mucous membrane. PHYSIOLOGICAL ACTIONS OF THE SALIVA. The most important action of the saliva is amylolytic or diastatic, that is, the conversion of starch into sugar and dextrin. This is due to the ptyalin, an unformed, hydrolytic ferment or enzyme which, even when present in small amounts, causes the starch to take up water and become soluble, with absorption of heat, although the ferment itself undergoes no material change. Ptyalin is not present in the saliva of true carnivora. According to Dubrunfaut, O' Sullivan, Musculus and v. Mering, maltose and dextrin, both soluble in water, are formed from starch (or glycogen) by the dias- tatic ferment of the saliva (and of the pancreas) : PHYSIOLOGICAL ACTIONS OF THE SALIVA. 265 io(C 12 H 20 10 ) + 8(H 2 0) = 8(C 12 H 22 U ) + 2 (C 12 H 20 O 10 ) Starch + Water = Maltose + Dextrin. The exact course of events is as follows: At first with liquefaction of the starch-paste amylodextrin is formed. This does not reduce Fehling's solution; it is colored blue by iodin and is the principal constituent of the preparation formerly called soluble starch or amydulin. It is transformed into three molecules of erythrodextrin, which reduces Fehling's solution feebly, and is colored red by iodin. The erythrodextrin is transformed into three molecules of achroodextrin, which reduces Fehling's solution, but is not stained by iodin. From this iso- maltose and maltose are formed, the latter being formed from the former by the action of ptyalin. Isomaltose undergoes fermentation with greater difficulty than maltose. Finally all the starch is changed into maltose and dextrose. When little ferment is present and the action is of short duration, the saliva or the pancreatic juice produces isomaltose principally; when much ferment is pres- ent and the action is of longer duration, the formation of maltose and of some dextrose is favored. The maltose subsequently may be changed in the intestine into dextrose, but the greater part is absorbed unchanged. Kirchof, in 1811, showed that dextrose is formed from starch, by boiling with dilute sulphuric or hydrochloric acid. Demonstration of Ptyalin. This depends, as in the case of all hydrolytic fer- ments, upon the fact that a voluminous precipitate formed in the saliva carries the FIG. 96. Potato Starch. ferment down with it mechanically, and from it the latter is then isolated by simple means. For this purpose the saliva is strongly acidulated with phosphoric acic lime-water is added until the reaction is rendered alkaline. As a res precipitate of basic calcium phosphate forms, carrying the ptyalin down w This precipitate is collected upon a filter and the ptyalin is dissolved out the aid of a little water. Alcohol precipitates the ptyalm in this watery e as a white powder. By repeated solution in water, and subsequent precipitatic with alcohol, the ptyalin is obtained in an absolutely pure The cells of the glands first contain ptyalin in a preliminary stage a ptyalinogenic substance, from which ptyalin is formed only during . * Ptyalin contains nitrogen, is free from ash, but yields no xanthoproteic react It is precipitated from solution by neutral or basic lead acetate. deC T P Wi?t S ich y taS "ptval- could be extracted with glycerin containing water from the salivary glands of human beings or swine, cleansed, minced, 266 PHYSIOLOGICAL ACTIONS OF THE SALIVA. placed in strong alcohol and then dried. After standing for several days, the glycerin is poured off and to it alcohol is added, precipitating the ptyalin. This is collected on a filter and then dissolved in water. In order to free it from any albumin that may be adherent to it, the aqueous solution is rapidly heated to 60 C., with the result that the albumin is precipitated, while the ptyalin remains unimpaired in solution in the filtrate. The following details are worthy of consideration with respect to the action of the saliva in the process of saccharification: (a) The process of saccharification is recognized: (i) from the disappearance of the starch. The addition of a little iodin to a thin solution of starch produces a blue color. If, now, saliva is added and the liquid is shaken, the blue color quickly disappears. (2) Directly by demonstration of the presence of sugar by appropriate tests. (6) The process pursues a most favorable course at a temperature between 35 C. and 46 C.; it is slower in the cold; at 55 C. the action of the ferment be- comes weaker, and at 75 C. it is destroyed. Ptyalin is distinguished from diastase, that is the diastatic ferment formed in germinating grain, by the fact that the latter exhibits its saccharifying action only at a temperature between 60 and 69 C. Ptyalin also breaks up salicin into "saligenin and grape-sugar. (c~) The ptyalin, as a ferment, remains unchanged in the process of sac- charification. Nevertheless, when once employed, it will not possess the same activity in a second experiment. (d) The diastatic activity is greatest in the morning. It then declines, rising again toward noon and falling once more toward evening. It declines also after every ingestion of food. (e) The action of the saliva is most intense when its reaction is feebly acid, though it takes place also when the reaction is alkaline or neutral. Ptyalin causes the production of sugar in the acid gastric juice of human beings only when the acidity is due to organic acids, such as lactic or butyric acid, but not when it is due to free hydrochloric acid. The production of dextrin occurs in either event. In the former case, therefore, saccharification may be con- tinued in the stomach, although the ptyalin is destroyed by the hydrochloric acid or digested by the pepsin. The presence of peptone is said to be necessary for the production of sugar. The production of butyric and lactic acids in consid- erable amount may exert an inhibitory effect on the formation of sugar. Neutral- ization of these acids, however, permits the process to begin anew. (f) The addition of sodium chlorid, ammonium chlorid, or sodium sulphate (in about 4 per cent, solution) increases the fermentative activity of ptyalin, as do also the acetates of quinin, strychnin, and morphin ; further, curare and 0.625 per cent, sulphuric acid. (g) Much alcohol and potassium hydroxid destroy the ptyalin; exposure to the air for a considerable time weakens it; sodium carbonate and magnesium sulphate delay its action; while salicylic acid inhibits saccharification, as does also much atropin. (Ji) Ptyalin acts but feebly and gradually on unboiled starch only after the lapse of 2 or 3 hours; while it acts rapidly upon starch swollen by boiling (starch-paste) . (i) The different kinds of starch are transformed with varying rapidity in accordance with the quantity of cellulose contained in each: unboiled potato- starch (Fig. 96) in not less than 2 or 3 hours; unboiled corn-starch within 2 or 3 minutes; wheat-starch more quickly than rice-starch. When rubbed up into powder or boiled, all starches act in the same way. (fe) The mixture of saliva from all of the -glands is more effective than that from any one gland alone; the mucus is inactive. Ptyalin produces free hydrogen sulphid from radishes, onions, garlic, and the like, which contain sulphur. This fact explains the presence of the gas named in the intestines after the ingestion of the foregoing substances. The saliva takes part in dissolving in the mouth articles of food soluble in water. The saliva moistens articles of food ingested in a dry state, renders possible, by its viscosity, the formation of the bolus and facilitates deglutition through the slipperiness afforded by the mucus it contains. The mucus is later evacuated with the feces. TESTS FOR SUGAR. 267 Recently the presence of peptone-producing ferments in the saliva has been discovered, but they are perhaps merely absorbed from the intestine and again excreted in the saliva (as occurs in the urine). TESTS FOR SUGAR. Trammer's test, like several others, depends upon the fact that sugar in hot alkaline solution acts as a reducing agent; here a metallic oxid is transformed into a suboxid. To one-half as much potassium-hydrate or sodium-hydrate solution, of a specific gravity of 1.25, is added the fluid to be tested. Then a weak solution of cupric sulphate is added drop by drop until the bluish precipitate that appears at first and consists of cupric oxid, is again dissolved by agitation. If sugar is present, the precipitate again forms a deep-blue solution after agitation. If heat is applied gradually almost up to the boiling-point a yellowish or reddish cloud is formed from above, which is finally precipitated as brownish- red cuprous oxid or as yellowish-red cupric oxid: 2CuO O = Cu 2 O. Cuprous oxyhydrate is dissolved also by other organic substances, though only certain sugars maltose, grape-sugar, fruit-sugar and milk-sugar, but not cane- sugar cause final reduction. Fluids previously turbid must be filtered and possibly treated with basic lead acetate. In the latter event the excess of lead is precipi- tated by sodium phosphate; then filtration is practised. When the amount of sugar is exceedingly small, concentration of the fluid over the water-bath may be necessary. If small amounts of sugar, less than 0:5 per cent., are present, to- gether with ammonia, uric acid, and kreatinin, instead of a yellow precipitate, merely a yellow solution of cuprous oxid may result. The addition of an excess of cupric sulphate, which should always be avoided, causes confusion by the precipitation of black cupric oxid. Bottger's test is made with an alkaline solution of bismuth oxid, best prepared according to Nylander as follows: Bismuth subnitrate 2 grams, sodio-potassium tartrate 4 grams, and sodium hydrate (8 per cent.) 100 grams. One cu. cm. of this mixture is added to 10 cu. cm. of the fluid to be tested. Upon boiling for several minutes the sugar present causes reduction to metallic bismuth, with the formation of a black precipitate. Moore's and Heller's test: Sufficient sodium or potassium hydrate is added to the fluid to give it a strongly alkaline reaction. On boiling, a yellowish, brownish or brownish-black color results from the formation of humus-substances. If, after cooling, one drop of concentrated sulphuric acid is added, the odor of burnt sugar (caramel) and formic acid develops. Mulder's and Neubauer's test: If a solution of indigo-carmin, made alkaline by sodium carbonate, is added to a fluid containing sugar until a pale-blue color is produced, and heat is applied, the color becomes successively green, purple, reel and yellow. Agitated with atmospheric air the fluid again acquires the blue color. Molisch's tests: To cu. cm. of the fluid to be tested, 2 drops of a 17 per cent, alcoholic solution of a-naphthol or of a solution of thymol are added ; with dilute solutions of sugar a small quantity of solid a-naphthol may be used instead of the solution. Then i or 2 cu. cm. of concentrated sulphuric acid are added and the fluid is rapidly shaken. In the presence of sugar the a-naphthol mix- ture becomes deep violet in color, the thymol-solution deep red. Subsequent dilution with water causes a precipitate of the same color, which is insoluble in concentrated hydrochloric acid. Albumin, casein and peptone also yield this reaction, but the precipitate appearing upon the addition of water is solubl< in concentrated hydrochloric acid. Phenylhydrazin test: To 7 cu. cm. of the fluid in a test-tube a small amoun of phenylhydrazin chlorid (0.2) and also of sodium acetate (0.3) are added. Heat is applied until solution takes place, water being added if necessary, kept in boiling water for an hour. The contents are then poured into a conical glass, at the bottom of which characteristic yellow, microscopical tufts of fine, long needles of phenylglucosazone are found, which are almost insoluble in water; while maltose produces an analogous substance, phenylmaltosazone, which is soluble in hot water. From all fluids to be tested for sugar, any albumin present should first removed; from the urine by boiling, after slight acidulation with acetic acid from the blood, by the method described on page 73; the alcohol is driven heat. 268 QUANTITATIVE ESTIMATION OF SUGAR. QUANTITATIVE ESTIMATION OF SUGAR. By Fermentation. (An illustration of yeast is given in Fig. 140.) For this purpose the apparatus illustrated in Fig. 97 is employed. In the glass flask a is measured a quantity (as, for example, 20 cu. cm.) of fluid containing sugar, to which yeast is added. The flask b contains concentrated sulphuric acid. The entire apparatus is weighed immediately after being filled. At ordinary tem- perature (between 10 and 40 C.), most energetically at 25 C., the sugar breaks up into 2 molecules of alcohol and 2 molecules of carbon dioxid : C 6 H 12 6 = 2 (C 2 H 6 0) Sugar = 2 Al 2(C0 2 ) 2 Carbon dioxid. FIG. 97. A In addition some glycerin and succinic acid are formed. The carbon dioxid escapes through the flask b, and returns to the sulphuric acid any water that it may have taken with it. If the decomposition is concluded in the course of about two days, the apparatus is again weighed. From the loss in weight the amount of sugar that was contained in the 20 cu. cm. of fluid is estimated, in accordance with the fact that 100 parts by weight of sugar free from water are equal to 48.89 parts of carbon dioxid, or that 100 parts of carbon dioxid by weight correspond to 204.54 parts of sugar. By Titration, with Fehling's alkaline cupric-oxid solution based on Trommer's test. The deep-blue titration-fluid, composed of cupric sulphate, potassium ace- tate, sodium hydrate and water, is so prepared that all of the cupric oxid in 10 cu. cm. of the solution will be reduced to yellowish-red cuprous oxid by just 0.05 gram of grape-sugar. For example, as in determining the amount of sugar in urine, 10 cu. cm. of Fehling's solution are placed in a porcelain dish, and gradually IPil diluted with 40 cu. cm. of water and heat > ^ ^. applied almost up to the boiling-point. The urine, previously diluted to from 10 to 20 times its volume, is dropped from a burette into the hot titration-solution, and stirred until every trace of blue color has disappeared or until one drop of the fluid no longer produces a red color on blotting-paper saturated with acetic acid and potassium ferrocyanid. The amount of urine needed is now read from the scale of the burette, making allowance for the dilution, and it will then be known that the amount of urine used for reduction contained 0.05 gram of grape-sugar. From this the amount of sugar in the entire quantity of urine excreted can be readily estimated. By Polarization. Sugar possesses the peculiarity of turning the plane of polar- ized light to the right, just as albumin turns it to the left. Specific polarizing power is the term applied to the degree of rotation that i gram of the substance in question, dissolved in i cu. cm. of water, forming a layer 10 cm. thick, the length of the tube of the apparatus, effects with yellow "light. For dextrose this is +56. As the rotatory power is directly proportional to the quantity of the substance dissolved in the fluid, the degree of deflection affords informa- tion as to the amount of the optically active substance contained in the fluid. In making the observation, the Soleil-Ventzke polarization-apparatus (Fig. 98) shows on its scale to the right directly the percentage of sugar; to the left, that of albumin. The light derived from the lamp encounters a crystal of calcspar at a. Two Nicol's prisms are placed at v and s; that at v can be rotated about the visual axis, while the other is fixed. The Soleil double plate of quartz is attached at m; one-half of this deflects the plane of polarized light as far to the right as the other deflects it to the left. At c the field of vision is covered by a plate of levorotatory quartz. At b c is placed a compensator formed of two dextrorotatory prisms of quartz, which can be moved laterally by means of the screw g in such a way that the polarized light sent through the apparatus must pass through a thinner or thicker layer of the dextrorotatory quartz in accordance with the degree of rotation. With these dextrorotatory prisms in a certain position, the deflection of the levorotatory quartz at n is exactly neutralized. In this position the scale and vernier placed upon the compensator will be exactly at O, and both atus for the Quantitative imation of Sugar. QUANTITATIVE ESTIMATION OP SUGAR. 269 halves of the double plate at m appear of the same color to the observer, who looks from v through the telescope introduced at e. By appropriate rotation of the Nicol s prism at v, a bright rose color is preferably selected fn this position the telescope must be so adjusted that the vertical dividing line of the double plate is plainly visible. Thus adjusted the instrument is ready for use The tube, 10 cm long, is filled with the fluid to be examined, which must be perfectly clearshould it contain albumin, this must be removed by boiling and filtering - and the tube is introduced into the apparatus between m and n. By rotating the Nicol s prism at v, the rose-red color is again brought into view. Then the com- FIG. 98. The Soleil-Ventzke Saccharimeter. pensator at g is turned until both halves of the field of vision are exactly of the same color. When this has been done, the number of divisions the zero-mark of the vernier has been moved to the right in the case of albumin to the left can be read directly from the scale. The number of divisions read off shows directly the number of grams of the rotatory substance in 100 cu. cm. of the fluid. Turbidity that persists in spite of filtering often disappears after addition of a drop of acetic acid or a few drops of a solution of sodium carbonate or lime- water, with subsequent filtration. For a description of other apparatus employed for the same purpose the polaristrobometer of Wild, the polarimeter of Zeiss, 270 THE MECHANICS OF THE DIGESTIVE APPARATUS. and the half-shadow apparatus of Laurent, Lippich, and others the text-books on physics and chemistry should be consulted. THE MECHANICS OF THE DIGESTIVE APPARATUS. The mechanism of the digestive apparatus comprises : 1. The prehension of the food, the movements of mastication and of the tongue, insalivation, and the formation of the bolus. 2. The movements of deglutition. 3. The movements of the stomach and the small and large intestines. 4. The expulsion of fecal matter. THE PREHENSION OF FOOD. Liquid food is taken into the mouth (i) by suction. While the lips are applied hermetically about the utensil containing the fluid, the tongue, moving downward and at the same time flattened, often in conjunction with depression of the lower jaw, causes the fluid to enter the buccal cavity. Herz found that the negative pressure produced by the suction of infants equals from 3 to 10 mm. of mercury. (2) The liquid is sipped when it is brought directly in contact with the lips, and then is drawn by aspiration into the buccal cavity, together with air, with a characteristic sound. (3) Liquid can also gain entrance into the buccal cavity by being poured, the lower lip, as a rule, being applied to the containing vessel. Among the solid articles of food, the smaller particles, supported by the lips, are picked up by the tongue; of the larger particles a piece is bitten off by the chisel-shaped incisor and sharp canine teeth, and then, for further comminution, it is brought between the rough surfaces of the bicuspid and molar teeth. THE MOVEMENTS OF MASTICATION, The articulation of the lower jaw is divided into two cavities, one above the other, by an interarticular cartilage, which also fulfils the duty of preventing mutual direct pressure of the articular surfaces during the energetic action of the muscles of mastication, in the act of chewing. The articular capsule, considerably strengthened by the external ligament particularly, is so capacious as to permit, in addition to elevation and depression of the lower jaw, also of displacement of the head of the inferior maxilla forward upon the articular tubercle, although the meniscus does not leave the head of the bone, which it covers like a cap. The movements of mastication include: (a) Elevation of the jaw, which is effected by the united action of the temporal, masseter and internal pterygoid muscles. If the inferior maxillary bone had pre- viously been greatly depressed, so that the condyles of the bone were moved forward upon the articular eminences, they now drop back into the articular cavity. If, in raising the lower jaw, the bone is maintained in a particular position, the action of the muscle that would move the maxilla from this position is lost, as is shown by the following: (i) In elevating the lower jaw when it is pushed as far forward as possible, the action of the temporal muscles is lost, because these, in raising the jaw, draw it backward at the same time. (2) When the lower jaw is pushed as far backward as possible, the temporal muscles alone exert an ele- THE MOVEMENTS OF MASTICATION. 271 vating action, because the other muscles would tend also to draw it 'forward at the same time. (3) When the lower jaw is displaced laterally, the elevating action of the temporal muscles is lost. (b) The downward movement of the lower jaw is partly due to its weight and partly to moderate contraction of the anterior bellies of the digastric and by the mylohyoid and geniohyoid muscles. These mus- cles act more powerfully when the mouth is opened widely and forcibly. The fixation of the hyoid bone necessary for this purpose is effected by the omohyoid and sternohyoid, as well as the combined action of the sterno thyroid and thyrohyoid muscles. As the articular heads of the bones move forward upon the articular tubercles when the inferior maxilla is greatly depressed, it has been assumed that, in this case, the external pterygoid muscles actively favor this displacement. When the mouth is opened to an especially marked degree, the head is bent backward, and, with the hyoid bone fixed, the posterior bellies of the digastric muscles, as well as the stylohyoid muscles, enter into action. Some animals possess upper jaws capable of movement upward and downward, as, for instance, parrots, croco- diles, snakes, and fish. (c) Displacement of one or of both articular heads of the inferior maxillary bone forward or backward, (i) Projection forward of the lower jaw is caused by the action of the external pterygoid muscles. As under such circumstances the articular head of the bone slips upon the articular tubercle, and therefore also moves downward, the surfaces of the lateral teeth must separate from each other in this position. (2) Backward displacement is caused by the action of the internal pterygoid muscles. (3) The articular head on one side is drawn for- ward and then backward again by the external and internal pterygoid muscles of the same side, a transverse movement of the inferior maxilla taking place at the same time. The more the lower jaw is depressed, the more ineffective are these movements. In the movements of mastication, with which both elevation and de- pression of the lower jaw, as well as with a transverse grinding movement are often combined, the food to be masticated is kept between the opposing surfaces of the teeth by the muscles of the lips (orbicularis oris) and the buccinators from without and by the action of the tongue from within. The sensibility of the masticatory muscles, together with the sensibility of the teeth and the mucous membrane of the mouth and lips, determines the amount of force to be expended by the muscles of the lower jaw for the purpose of mastication. By reason of simultane- ous insalivation, the divided particles cohere, so that they can be readily formed into an oval bolus on the dorsum of the tongue. The muscles of mastication, together with the mylohyoid and the anterior belly of the digastric, receive their motor nerves from the motor portion of the third division of the trigeminal nerve. The hypoglossal nerve innervates the geniohyoid, thyrohyoid, omohyoid, and sternohyoid muscles, as well as the sterno- thyroid. The buccinator, the posterior belly of the digastric, the stylohyoid and the muscles of the face that take part in opening and closing the mouth are sup- plied by the facial nerve. The common nervous center for the movements o mastication lies in the medulla oblongata. When the mouth is shut, the permanent position of the jaws in contact with each other is due to atmospheric pressure, as the buccal cavity is made completely free of air, while the entrance of air is prevented anteriorly by the lips and pos- teriorly by the veil of the palate. The pressure of the atmospheric air corresponds to a column of mercury of from 2 to 4 mm. high. 272 STRUCTURE AND DEVELOPMENT OF THE TEETH. STRUCTURE AND DEVELOPMENT OF THE TEETH. The tooth is to be regarded as a modified papilla of the mucous membrane of the jaw, of exceptional size and peculiar structure. In its simplest form it appears as a horny tooth, as, for instance, in the lamprey and the duck-bill, in which the connective-tissue framework of the papilla is covered externally with layers of hard, horny epithelium, comparable with the formation of hair and of bristles. In the formation of human teeth a thick layer covering the papillary cone is transformed into the firm layer of calcified dentine. The epithelium of the papilla produces the enamel, while an accessory deposit takes place around the base of the cone in the form of a thin covering of bone (cement) . The dentine, ivory, or tooth-bone, which surrounds the cavity of the tooth (Fig. 99) and the root-canal, is firm, elastic and brittle. It appears, when subjected to special treatment, to be composed of fibrils, which unite to form lamellae, and these in turn make up the dentine and are traversed perpendicularly by the dentinal tubules. These numerous, long, corkscrew-like, spiral dentinal tubules begin with free openings from 1.3 // to 2.2 u in diam- eter in the interior of the tooth, and traverse the dentine to its outermost layer. The tubtiles are bounded by an extremely resistent, thin cuticle-like layer, the dentinal sheath (Fig. 100), which is most unyielding to chemical agents. Within the cavities of the dentinal tubules and completely filling them lie soft fibers, the dentinal fibrils, which are to be con- sidered as enormously elongated processes from the superficial pulp-cells, the odontoblasts. The dentinal tubules, and also their con- tents, the dentinal fibrils, anastomose throughout their entire course by means of processes. Most of them terminate near the enamel, or they penetrate by means of delicate processes into the cement substance between the enamel prisms. Only a few bend over, forming an arch and joining one another (Fig. 102, A, c}, while others pass over into the interglobular spaces (Fig. 101). The latter are small, uncalcified areas of the ground-substance, or dilated tubules located in greater number particularly near the periphery of the dentine, and bound by spherical surfaces. With the naked eye peculiar lines can be seen in the dentine, particularly that of the elephant's tooth, running parallel with the contour of the tooth (Schreger's lines) , which depend upon the fact that, at these points, all of the dentinal tubules pursue a similar course as respects their main curves. A special canal- system, rising from the root, lies between the dentine on one side and the enamel and cement on the other, and communicates with the other cavities of the tooth. The enamel (vitreous substance), the hardest substance in the body, as hard as apatite or quartz, covers the free projecting crown of the tooth. It consists of perpendicular, hexagonal prisms (Fig. 102, B, C), arranged side by side like palisades, and united by cement-substance. These prisms are from 3 fi to 5 p wide, varying in thickness throughout their course, at the same time arching in different directions, and they exhibit, after the action of acids, a coarse, trans- verse striation, which, however, is absent in entirely fresh prisms. As regards their nature, the enamel-prisms are elongated and calcified cylindrical epithelium of the dentinal papilla. Retzius described, in enamel, the presence of dark, brownish bands, running parallel to the outer border of the enamel^ and due to the deposition of air in the enamel (Fig. 99). Fully formed enamel is in marked degree negatively doubly refracting and uniaxial, while developing enamel is posi- tively doubly refractive. The cuticula, the membranous capsule of the enamel, covers the free surface FIG. 99. Longitudinal Section through an Incisor Tooth: s, enamel; d, dentine; cd, tooth-cavity; c, cement. STRUCTURE AND DEVELOPMENT OF THE TEETH. 273 FIG. 100. Transverse Sec- tion through Dentine. The light rings are the dentinal sheaths, the dark centers with the bright points are the dentinal fibrils lying in the dentinal tubules. of the enamel as a structureless membrane, i /n or 2 fi thick, which, in the case of young teeth, exhibits an epithelium-like arrangement, and is derived from the outer epithelial layer of the enamel organ. The cement (osseous substance) consists of a thin bony layer covering the root of the tooth, with a nbrillated ground-substance and provided with Shar- pey's fibers (Fig. 103, a). Haversian canals and lamellae are found only in the thick layers of cement at the apex of the root, the former at times leading into the tooth-cavity. Thin layers of cement may even be unprovided with bone-corpuscles. Chemistry of the Solid Constituents of the Tooth. The teeth consist of a framework of calcareous sub- stance, infiltrated with calcium phosphate and car- bonate, like the bones, (i) The dentine contains of organic matter 27.7, of calcium phosphate and car- bonate 72.06, of magnesium phosphate 0.75, with traces of iron, fluorin and sulphuric acid, potassium, sodium, and carbon dioxid. (2) The enamel pos- sesses as its organic basis a substance resembling the proteid of epithelial cells. It contains of inor- ganic matter in addition to 3.60 of organic matter calcium phosphate and carbonate 96.00, magnesium phosphate 1.05, with traces of calcium fluorid, an in- soluble chlorin-combination, potassium, sodium, and carbon dioxid. (3) The composition of the cement is identical with that of true bone. The Soft Parts of the Tooth. The tooth-pulp in the adult tooth represents the remains of the dental papilla, about which the hard- ening layer of dentine has been deposited. It consists of connective tissue, at times not distinctly fibrous, and rich in capillaries, with connective-tissue cells and leukocytes. The most superficial layer of cells, which, not unlike epithelium, lie close together next to the dentine, is formed of unencapsulated odontoblasts, 25 // long by 2 fi wide, from which the production of the dentine proceeds. They send long processes into the den- tinal tubules, while the nucleated cell- body, resting on the surface of the pulp, forms a connection with the pulp and with neighboring odontoblasts by means of other processes. Numerous medullated nerve-fibers, becoming non- medullated after repeated division, penetrate between the odontoblasts and end beneath the dentine in free ex- tremities presenting nodular thickening in places. Other nerve-fibers lie partly in the dentinal tubules, in part in the substance of the dentine. Most of them appear to end free, in a brush-like radiation. A plexus of fine nerve-fibers lies beneath the enamel. The epidenti- nal canal-system is provided with a special nerve-apparatus, which in part penetrates into the enamel. The ar- teries of the tooth often lie in grooves in the nerve-branches. The capillaries even penetrate to the odontoblast-layer. The periosteum of the root of the tooth and, at the same time, of the alveolar cavity, is of a delicate structure, without elastic fibers, but rich in nerves and blood-vessels. The gums have no mucous glands and are characterized by their long, vascular papillae. The development of the teeth begins as early as the fortieth day (Rose). Throughout the entire length of the alveolar margin there is a projecting ridge, formed of a thick epithelial layer, the denial ridge (Ing. 104, a). From this epitne- 18 FIG. 101. Interglobular Spaces in the Dentine. 274 STRUCTURE AND DEVELOPMENT OF THE TEETH. lial layer a furrow, also filled with epithelium, forms in the jaw, the dental groove, which thus runs beneath the base of the dental ridge. The dental groove grows deeper throughout its entire length, acquiring a form resembling the transverse sec- tion of elongated formative epithelial cells; this is the enamel organ. From the depth of the jaw there grows toward the enamel organ a conical papilla, formed of mucous tissue, the dentinal papilla (Fig. 104, c), in such a way that its apex sup- FIG. 102. ,4, Section of a Tooth at the Junction (6) between Dentine and Enamel: a, enamel; c, dentinal tubules; B, enamel prisms greatly magnified ; C, the same prisms in transverse section. ports the enamel organ like a double cap. The connecting parts of the enamel organ, lying between the dentinal papillae of the separate teeth, now disappear, through hyperplasia of the connective tissue, which next gradually surrounds the dentinal papilla and its enamel organ as the dental sac (Fig. 104, d, Fig. 105). Of the epithelial cells of the enamel-organ those (Fig. 105, 3) that cover the head of the papilla as a continuous layer form cylindrical epithelium, which later, FlG. 103. Transverse Section of the Root: a, cement, with bone-corpuscles; &, dentine with dentinal tubules; c, junction between the two. a FIG. 104. a, Dental ridge; b, enamel orga.n; c, site of the beginning dentinal papilla; d, first trace of the dental sac. bv calcification, hardens into the enamel prisms. The layer of cells of the double cap however, which is turned upward toward the dental sac (Fig. 105, i), flatten! out softens down and through a process of horny metamorphosis becomes the cuticula while the epithelial cells lying between the two layers gradually under- go complete atrophy through a peculiar intermediary metamorphosis in which they resemble the star-shaped cells of mucous tissue (Fig. 105, 2). Accordi STRUCTURE AND DEVELOPMENT OF THE TEETH. 2 75 v. Brunn the enamel extends along down the entire root of the tooth during the process of development, but is subsequently lost in this situation. The dentine is formed on the uppermost surface of the protruding connective- tissue dentinal papilla, the odontoblasts (Fig. 105; Fig. 106, k) arranged here in a continuous layer becoming calcified, but in such a manner that uncalcified fibers, the dentinal fibrils, remain. "By means of the process of the pulp each odonto- blast is connected with the deeper lying, grad- ually growing cells of the young pulp, so that when an odontoblast is ossified down to the rudiment of its fibril another takes its place, without the continuity of the fibril being inter- rupted. Accordingly, each dentinal fibril with its anastomoses, must be considered as a rudi- ment of several communicating odontoblasts." In the hardening of dentine the same process occurs as in that of ossification by osteoblasts. The cement is derived from the soft connec- tive tissue of the alveolar process by ossification. This connective tissue arises from the entire base of the dental sac. The Shedding of the Teeth. Even during the development of the milk-teeth, a special enamel organ (Fig. 105, c) for the permanent teeth forms by the side of that for the temporary teeth ; but its growth is held in check until the FlG - 105. a, Dental ridge; 6, enamel or- time for the shidding of the teeth. The papilla ^^^S^^S of the permanent tOOth IS absent at the begin- a mel cell layer; c, dentinal papilla, ning. As the permanent tooth grows, its dental with blood-vessels and layer of elon- sae first breaks through the alveolar wall of the ffitSdtSfcS^ temporary tooth from below. The tissue of this dental sac, acting as an eroding granulation- tissue, causes absorption of the root of the temporary tooth and later also of its body, up to the crown, without its blood-vessels undergoing atrophy. The ameboid cells of the granulation-tissue engage in a process of undermining in the absorption of the temporary teeth by means of processes they send out, taking up, like phagocytes, calcareous fragments of the disintegrating tooth. From the ninth month to the second year the twenty temporary teeth appear in the following order: lower internal incisors, a upper internal incisors, upper external inci- sors, lower external incisors, first molar, canine and second molar teeth. The shedding of the teeth begins in the seventh year, in the same order (the decidu- ous molars being replaced by the bicuspids) . Then three new molars appear behind the bicuspid teeth, the most posterior at about the age of twenty years, therefore called "wisdom-teeth." They may, however, ap- pear as late as the eightieth year. Thus, the adult has thirty-two teeth. According to Zuckerkandl, epithelial re- mains are found in the gums behind the last molar teeth, which must be regarded as the rudiment of a fourth undeveloped molar tooth. An analogous condition has been noted in animals. The uninterrupted growth of the incisor teeth may be readily observed in rodents, replacing the free ends worn off by chewing. If the opposing incisor teeth of a rodent are extracted, the remaining teeth, no longer worn off by mutual attrition, grow from the jaw in the form of a long arch. That in human beings also a continual replacement of the teeth must occur canno be doubted. Landois has observed the advance toward the masticating si and the final disappearance in from 8 to 9 years of rachitic, atrophic, circul zones that must have formed on the permanent teeth of a boy even before FIG. 106. a, Dental ridge; b, enamel organ; c, dentinal papilla; /, enamel; g, dentine; h, gap between enamel organ and den- tinal papilla; k, odontoblast layer. 276 MOVEMENTS OF THE TONGUE. eruption. This proves the forward growth and the wear of the teeth at their free ends. Only when, in old age, the power of regeneration becomes diminished, do the teeth have worn-off surfaces. During the embryonal life of the baleen whale, dental sacs are noted in the jaws, which, however, undergo atrophy; in their place whalebone develops later. Tooth-bearing edentates, whose teeth are unprovided with enamel, nevertheless possess an enamel-organ, whose function it is, like a matrix, to insure for the developing tooth sufficient room for its forma- tion. The edentulous armadillo possesses an embryonal dental ledge, which has also been found in birds and turtles as the last rudiment of a former den- tition. MOVEMENTS OF THE TONGUE. The tongue keeps the food between the opposing surfaces of the teeth during mastication; it collects the finely divided particles of food, held together by the saliva and forms them into a bolus, and finally it trans- fers the bolus along its dorsal surface into the pharynx at the time of deglutition. The course of the muscle-fibers in the tongue is three-fold: longitudinal, from the tip to the root of the tongue; transverse, originating mainly from the septum of the tongue stretched longitudinally; and vertical, traversing the thickness of the organ. The muscles of the tongue are in part confined to this organ alone; in part they pass to the tongue from other fixed points, namely, the hyoid bone, the lower jaw, the styloid process and the palate. Microscopically the muscle-fibers are striated transversely, surrounded by deli- cate sarcolemma, and frequently divided like a fork at their extremities. The bundles interlace with one another to a considerable extent, and small deposits of fat are found in the spaces between them. The movements of the tongue give rise in part to changes in form, in part to changes in position. 1. Shortening and widening, through the longitudinal lingual muscle, aided by the hyoglossus. 2. Elongation and narrowing, through the transverse lingual muscle. 3. Excavation of the dorsum of the tongue in the form of a longitudinal furrow, through contraction of the transverse lingual muscle, with simultaneous action of the median vertical fibers. 4. Arching the dorsum of the tongue: (a) transversely, through contraction of the lowermost transverse fibers; (6) longitudinally, through the action of the lowermost longitudinal muscles. 5. Protrusion of the tongue, through the genioglossus, aided somewhat by the geniohyoid, passing from the hyoid bone toward the chin; at the same time the tongue usually becomes elongated and narrowed. 6. Retraction of the tongue through the hyoglossus, chondroglossus and stylo- glossus; also as a rule with shortening and widening of the tongue. 7. Depression of the tongue upon the floor of the mouth is effected in the median line by the genioglossus; at the sides by the hyoglossus. By depression of the hyoid bone the floor of the mouth can be made even much deeper. 8. Elevation of the tongue to the palate: (a) at the tip, through the anterior portions of the upper longitudinal fibers; (6) in the center, through elevation of the entire hyoid bone by the mylohyoid muscle (trigeminal nerve) ; and (c) at the root, through the styloglossus and palatoglossus muscles, as well as indirectly by the stylohyoid muscle (facial nerve) . 9. Lateral deflection of the protruded tongue is effected by the genioglossus (toward the opposite side) ; while similar deflection of the tongue, lying in the mouth, is effected by the styloglossus, hyoglossus, chondroglossus and palato- glossus muscles. Further lateral deflection of the tongue, so that the tip comes to lie behind the last bicuspid tooth, is effected through the combined action of the styloglossus and Hyoglossus muscles on one side and the genioglossus on the other side. The motor nerve of the tongue is the hypoglossal. In case of unilateral paralysis the tip of the tongue lying at rest in the mouth is directed toward the unaffected side, because the tone of the unparalyzed longitudinal fibers shortens the unaffected side to some extent. If, however, the tongue is protruded, the tip deviates toward the paralyzed side. This is dependent on the direction pursued by THE ACT OF SWALLOWING. 277 the genioglossus muscle from the middle line (internal mental spine) backward and outward, the direction of whose traction the tongue must naturally follow. The tongue in killed animals sometimes exhibits fibrillary twitchings for an entire day. THE ACT OF SWALLOWING (DEGLUTITION). The propulsion of the contents of the alimentary canal is effected by a motor process whereby the canal contracts upon the contained mass; and as this contraction progresses throughout the entire length of the tube, the contents are pushed on before it. This movement is called peristalsis. The first and most complicated act of this movement is deglutition, in which the following stages can be distinguished : 1. The mouth is closed by the orbicularis oris muscle (facial nerve). 2. The jaws are pressed together by the muscles of mastication (trigeminal nerve); in this way the lower jaw becomes a fixed point, permitting the action of the muscles passing from the lower jaw to the hyoid bone. 3. The tip of the tongue, the back of the tongue, and the root of the tongue are successively pressed against the hard palate, and in this way the contents of the mouth Hjolus or fluid) are forced toward the pharynx. 4. When the bolus has passe^j^e anterior palatine arches, having been made slippery by the mucus of the tonsillar glands, its return % the mouth is prevented by the contraction of the palatoglossus muscles lying in the anterior palatine arches, which bring these arches firmly in contact with each other, like the scenes in a theater, and by the back of the tongue, which is elevated by the styloglossus muscle. 5. The bolus now lies behind the anterior palatine arches and the root of the tongue, within the pharynx and exposed to the succes- sive action of the three constrictor muscles of the pharynx, which push it onward. The action of the superior constrictor muscle, which contracts first, is always combined with horizontal elevation, through the elevator of the veil of the palate (facial nerve), and tension of the soft palate, through the tensor of the veil of the palate (trigeminal nerve; otic ganglion). The superior constrictor, through the pterygo- pharyngeal muscle, presses the posterior and lateral pharyngeal wall firmly against the posterior edge of the veil of the palate horizontally elevated and made tense like a cushion (Passavant's cushion), while the edges of the posterior palatine arches are at the same time approximated through the palatopharyngeal muscles. In this way the nasopharyngeal cavity is closed, so that food is prevented from passing readily upward into the nasal cavity. In persons with congenital or acquired defects of the soft palate, food can enter the nose during the act of deglutition. The elevation of the veil of the palate can be readily demonstrated by intro- ducing a fine probe through one nostril, along the floor of the nasal cavity, until its posterior extremity rests upon the veil of the palate. With every movement of ~ from the nostril, is nected with a gas-pipe, the other with a burner. Every movement of deglutition is attended by movement of the flame. 278 THE ACT OF SWALLOWING. 6. Responding to the successive contractions of the superior, middle, and inferior constrictors of the pharynx and the esophageal muscles, the bolus is forced downward. During this time the entrance to the larynx must be kept closed, to prevent food from passing into the trachea. 7. According to Kronecker and Falk, semisolid foods and fluids in the mouth are forced through the pharynx and the esophagus by vigorous contraction of the muscles closing the mouth, particularly the mylo- hyoid muscles. If the act of swallowing is repeated several times in rapid succession, as in drinking, only the last is followed by movements of contraction in the pharynx and the esophagus, for every act of swallowing in the mouth exerts an inhibitory effect upon the lower portions of the esophagus, through stimulation of the glossopharyngeal nerve. That solid and semisolid articles of food are, however, pushed slowly through the esophagus, by peristalsis alone, has been demonstrated by the Rontgen rays on admixture of bismuth subnitrate with the bolus. According to Meltzer and Kronecker, the duration of the act of deglutition in the mouth is 0.3 second. Then the constrictors of the pharynx contract; 0.9 second later the superior, 1.8 seconds later the middle, and 3 seconds later the inferior constrictor of the pharynx. The constriction of the cardiac orifice, after the food has passed into the stomach, is th^Jinal movement of the series. On auscultation of the stomach two^^fcads are heard during deglutition: (i) the squirting sound, which is due to the^^^Pthat the material swallowed is forced irjgp the stomach, and (2) the squeezing !^md, due to peristalsis occurring at the end of deglutition forcing the contents of the esophagus through the cardia. The latter is a rale and, as such, is dependent on the presence of air in the mass swal- lowed. Closure of the larynx is brought about as follows: (a) The lower jaw being fixed, the larynx is drawn upward and forward beneath the root of the tongue, which is arched over it. This is effected by a movement of the hyoid bone forward and upward through the action of the geniohyoid, the anterior belly of the digastric, and the mylohyoid muscles together with an approximation of the larynx to the hyoid bone, through the thyro- hyoid muscle, (b) While the tongue, besides, is drawn somewhat backward by the styloglossus muscles, it presses the epiglottis over the entrance to the larynx, so that food can now slide over it. (c) The epiglottis, further, is pulled down over the entrance to the larynx by the action of the reflector epiglottidis and the aryepiglottic muscle. Intentional injuries of the epiglottis in animals, or destruction of the epiglottis in human beings, cause choking readily from the entrance of liquids into the larynx, while solid foods can be swallowed with scarcely any trouble. In dogs, however, colored liquids pass directly from the back of the root of the tongue downward into the pharynx, without necessarily staining the upper surface of the epiglottis, hidden under the overhanging root of the tongue. (d) Finally, closure of the glottis by the constrictors of the larynx prevents the entrance of swallowed substances into the larynx. This closure is brought about through reflex influences. In order that the pharynx itself shall not be drawn down with the de- scending bolus it is drawn upward by the stylopharyngeal, salpingo- pharyngeal and basopharyngeal muscles during the activity of the pharyngeal constrictors. Nervous Supply. The nerves of the pharynx are comprised in the pharyngeal plexus, formed by branches from the pneumogastric, the glossopharyngeal and the sympathetic. The act of deglutition' is voluntary- only in so far as it takes THE ACT OF SWALLOWING. 279 place in the mouth. The passage of the bolus through the palatine arches on ^ p ^^-^ e ^^ c ^-^^ nerves an question for the striated muscles lies in the medulla oblongata Degluti- rftSn'^LSS^ m rt Stat ? f unconsei usn ^s, as well as after destruction -,,ti .r P h P H,, m and pons. Irritation of the ninth cranial nerve prevents the S. Me. Within the esophagus (Fig. 107), the stratified squamous epithelium of which is kept slippery by the mucus from small mucous glands opening at the edges of the folds of mucous membrane, the downward movement takes place also involuntarily through a coordinated muscular act a peristaltic movement of the external (longitu- dinal) and the internal (circular) unstriated muscle-fibers. In the upper part of the esophagus, in which lie striated muscle-fibers, peris- talsis is much more rapid than in the lower portion. The movements of the esophagus never originate spontaneously, but they al- ways follow on a previous act of deglutition. Thus, if a bolus be introduced into the esophagus through an external wound, it re- mains where it was placed; it is carried downward only when movements of deglu- tition are initiated above. The peristalsis extends throughout the e h t i r e length of the esophagus, even if this be ligated or a portion has been excised. The peristalsis, likewise, continues downward in a dog, even after meat is with- drawn from the esophagus, though it has been halfway down. Exceedingly large and exceedingly small masses of food are swallowed with greater effort than those of medium size. Dogs are able to swallow a bolus weighing 450 grams. Deglutition becomes difficult in consequence of great dilata- tion of the thorax, as in Miiller's experiments ; likewise in consequence . of con- traction of the thorax, as in Valsalva's investigations. The motor nerve of the esophagus is the pneumogastric after division of which on both sides food remains in the esophagus, particularly its lower part. Goltz discovered the remarkable fact that the ganglionic plexuses situated in the esophagus and the stomach of the frog acquire greatly increased irritability when the brain and spinal cord or both pneumogastric nerves are destroyed. Esophagus and stomach contract vigorously like a string of pearls, even after slight irritation, while animals with an uninjured central nervous system swallow fluid introduced simply by peristalsis. It should be borne in mind that human beings with an enfeebled nervous system (hysteria) not rarely exhibit similar spas- modic contraction of the esophagus (globus hystericus). Schiff observed spas- modic contraction of the esophagus in dogs also after section of both pneumo- gastric nerves. The heart -beats are accelerated with each act of swallowing, while the blood- pressure falls, the need of respiration diminishes and some movements, such as labor-pains and erection, are inhibited. All of these movements are brought about through reflex influences. FIG. 107. Transverse Section through the Esophagus. E, epithe- lium ; St, mucous membrane ; Se, mucous gland ; Me, circular muscle-fibers ; Ml, longitudinal muscle-fibers ; G, capillaries ; B, connective tissue; S, submucosa. 280 THE MOVEMENTS OF THE STOMACH. THE MOVEMENTS OF THE STOMACH. VOMITING. Three methods are employed for determining the position of the stomach: (a) the introduction of a rubber bougie through the esophagus, whose passage along the greater curvature of the stomach can be palpated; (6) electric transillumina- tion of the stomach by means of a small round incandescent light attached to the extremity of a stomach-tube. The stomach is previously suitably dilated by the development of carbon dioxid from sodium bicarbonate administered; the interpretation requires great care ; (c) the Rontgen rays have also been em- ployed after filling the stomach with meat mixed with bismuth subnitrate, the latter being impervious to the x-rays. For registering the gastric ^ movements, a _ rubber bulb, introduced through an external gastric fistula in animals, and applied in various situations in the in- terior of the stomach, is employed. The bulb is connected with a writing-ap- paratus by means of a column of air. Einhorn has used the gastrograph in human beings. This consists of a metallic capsule attached to the extremity of a rubber tube, which is swallowed. With every movement of the stomach the metallic parts in the interior of the capsule are brought into contact, and thus employed to effect an electrical registration. A series of photographs taken with Rontgen rays also affords information as to the course of the movements and the evacuation of the gastric contents. The anterior surface of the empty stomach lies in a frontal position, with a slight tendency to the right and upward, while the posterior surface accordingly occupies the opposite position. When the stomach is moderately distended, the anterior surf ace . rises about the lesser curvature as an axis, so that it forms an angle of from 45 to 48 with the horizon. When the distention is more marked, the stomach comes progressively to occupy more nearly the horizontal position, so that its anterior surface gradually becomes the superior surface. The muscular coat of the stomach consists of an external or longitudinal layer of fibers, a middle or circular layer, and an internal or oblique layer, one layer passing, over into another in many places. At the pylorus the musculature forms a circular sphincter-rmiscle (sphincter of the pylorus) , whose fibers continue into the pyloric valve. At the cardiac orifice also the muscle-fibers are grouped into a sphincter muscle. The movements of the stomach are of two kinds : i . The rotatory- rubbing movement, by means of which the walls of the stomach lying in immediate contact with the ingesta move to and fro with a slow displacing action. These movements succeed one another periodically, each cycle occupying several minutes. These movements can be imitated by slowly rolling or mdlding a ball between the palms of the hands by means of rotatory movements of the hands in opposite directions. Indeed, hair swallowed by cattle and dogs is formed into a regular ball in the stomach. The object of this rotatory movement is thoroughly to moisten the surface of the stomach-contents with the secretion of the gastric glands, and at the same time to favor its escape by the pressure and the continu- ous passage of ingesta, as well as to detach the already loosened and softened superficial layers of the food. Further, the admixture of the ingesta with the gastric juice is effected in this way. This movement may be either diminished, in the presence of gastric disease, such as gastric ulcer, or increased, as when there is stenosis or dilatation. 2. The other kind of movement is a peristalsis of periodic recur- rence, in conjunction with rhythmic opening and closure of the pylorus, as a result of which the partly dissolved gastric contents are little by little propelled into the duodenum, commencing after an interval of fif- teen minutes and ending at about the fifth hour. Each wave lasts twenty seconds, with an interval of from fifteen to twenty seconds between waves. This peristalsis is most active from the pyloric antrum toward the pylorus. According to Rudinger, the longitudinal fibers passing toward the pylorus, in contracting, especially when the pyloric antrum is full, cause dilatation of the pylorus. THE MOVEMENTS OF THE STOMACH. 281 Evacuation of the stomach occurs only when the intestine is free from con- tents. The following experiment will serve to determine when the ingesta enter the intestine. In the presence of an alkaline reaction in the intestine, salol is decomposed into carbolic acid and salicylic acid; the latter can be recognized in the urine from the violet color produced upon adding ferric chlorid. In healthy persons this reaction begins in from half an hour to an hour and disappears after twenty-four hours; while in the presence of motor insufficiency of the stomach it is delayed from three to twenty-four hours. Liquids are rapidly propelled from the stomach into the intestine. The thick, muscular walls of the stomach in many grain-eating birds aid in triturating the ingesta. The energy of muscular action necessary for this purpose has often been measured by earlier investigators, who found that glass balls were broken, and lead pipes that could be flattened only by a pressure of 40 kilograms were compressed, in the stomach of the turkey. The masticating stomach of many insects also is capable of similar activity. Mechanical stimulation causes contraction of the muscular layers directly affected ; as does also application of potassium-salts, segmentary contraction of the circular muscles often taking place at the same time. Sodium-salts, on the con- trary, usually cause semicircular contractions or contractions progressing toward the cardiac orifice. At the pyloric antrum the stimulations as a rule spread more rapidly. Electrical stimulation of the internal surface of the stomach causes no movement. The contraction induced by stimulation of the intestinal mucous mem- brane is always less than that due to stimulation of the external surface of the in- testine. In human beings both endogastric and percutaneous electrical stimulation are without demonstrable effect on the evacuation and the secretion.of the stomach. Nervous Activity. Openchowski and his pupils make the following statements with respect to the influence of the nerves upon the movements of the stomach: The cardia contains automatic ganglion-cells, which are connected with the pneu- mogastric and the sympathetic nerves. A center for the contraction of the cardiac orifice is situated in the posterior quadrigeminal bodies, whence the paths pass downward, mainly through the pneumogastric, and in lesser degree through the splanchnic nerves. The center for opening the cardia lies in the corpus striatum, and in connection therewith one in the cruciate sulcus of the central cortex, in the dog; the pneumogastric nerves constitute the conducting paths. Dilatation centers are situated also in the upper portion of the spinal cord, whence the path passes through the sympathetic nerve (aortic plexus, lesser splanchnic nerve). Reflex opening of the cardiac orifice can be induced by irritation of the sensory splanchnic nerves, and of the sciatic also. The body of the stomach contains also automatic ganglia, connected with the pneumogastric and the sympathetic nerves. A center for contraction is situated in the corpora quadrigemina, whence paths pass through the pneumogastric nerves and the spinal cord, and from the latter into the sympathetic. The upper cord contains inhibitory centers; the paths pass through the sympathetic and the splanchnic nerves. The pylorus contains automatic ganglia. It exhibits a certain, varying degree of tone during closure: the splanchnic nerve may more fully open the pylorus, while the pneumogastric tends to close it. The center for opening the cardiac orifice inhibits the movement of the pylorus ; the path passes through the spinal cord and the splanchnic nerves. Inhibitory pyloric centers are situated in the corpora quadrigemina and the olivary bodies; the path passes through the spinal cord. The cortical center for opening the cardia causes simultaneous contraction of the pylorus; the path passes through the pneumogastric nerves. Centers for the contraction of the pylorus are situated in the corpora quadrigemina; the path passes through the pneumogastric nerves, a few fibers through the spinal cord and the sympathetic nerve. Stimulation of the peritoneum and also of the skin causes reflex of the pylorus and of the small intestine. Stimulation of the central of one pneumogastric, the other being intact, gives rise to immobility of the pylorus, contraction of the stomach and dilatation of the cardiac orifice, temperature to 25 C. causes movements in the excised empty stomach. Vomiting takes place in consequence of contraction of the walls of the s the pyloric sphincter being at the same time closed. It occurs most readily when the stomach is distended. Dogs usually distend the stomach greatly b vomiting, bv swallowing air. There is no doubt that in infants vomitl due principally to contractions of the walls of the stomach, though will 282 THE MOVEMENTS OF THE INTESTINES. the slightest spasmodic cooperation of abdominal pressure. When the act of vomiting is attended with straining, abdominal pressure comes energetically into play. The contractions of the walls of the stomach that cause a general diminution in the size of the viscus can be recognized when the stomach is exposed. The pylorus contracts ; then wave-like contractions appear from the pyloric extremity upward to the body of the stomach. The uppermost portion of the stomach, including the cardia, does not contract, but the cardiac orifice is opened by the con- traction of the longitudinal muscle-fibers, which pass toward the esophageal opening, and therefore must act as dilators when the stomach is full. The actual ejection of the contents of the stomach is immediately preceded by an eructation-like movement, dilating the intrathoracic portion of the esopha- gus. This takes place in such a manner that, with the glottis closed, violent, jerky inspiration suddenly occurs, causing the esophagus to be distended by gas rising from the stomach. At the same time the larynx and the hyoid bone are drawn forcibly forward by the combined action of the geniohyoid and sternohyoid, together with the stern othyroid and thyrohyoid muscles, with obliteration of the laryngeal angle. As a means of support the lower jaw is even moved horizontally forward; as a result air passes from the pharynx downward to the upper portion of the esophagus. At the same time the projection and the inclination of the head favor dilatation of the esophagus. If, now, sudden abdominal pressure is exerted, supported by the intrinsic movements of the stomach, the contents of the viscus will be ejected. If the vomiting be long continued, there may even be antiperis- talsis of the duodenum, as a result of which bile enters the stomach and becomes admixed with the vomited matters. Children, in whom the fundus of the stomach is not sacculated, vomit more readily than adults, in whom the fundus must contract forcibly. The center for the act of vomiting is situated in the medulla oblongata. It is connected with the respiratory center, as experience teaches that attacks of nausea can be overcome by rapid, deep respiration. The act of vomiting can be inhibited likewise in animals by means of artificial respiration. On the other hand, the administration of emetics does not permit the development of apnea. The act of vomiting may be excited by chemical or mechanical irritation of the centripetal nerves of the mucous membrane of the palate, the pharynx, the root of the tongue and the stomach; also, under certain conditions (pregnancy) by irritation of the uterus, of the intestines (peritonitis) , and also of the genito-urinary apparatus ; finally by direct stimulation of the vomiting center. The act of vomiting excited by repulsive conceptions appears to result from the transmission of stimuli from the cerebrum through conducting fibers to the vomiting center. The act of vomiting is also common in connection with cerebral disease. Irritation of the central stump of the pneumogastric nerve is capable of inducing vomiting. The ruminating process in ruminants resembles the act of vomiting. Also in human beings eructation of food resembling morbid rumination has been observed as the expression of a gastric neurosis. There exists under such circumstances relative insufficiency of the cardiac orifice of the stomach : with the glottis closed, the contents of the stomach on attenuation of the air in the thorax rise into the mouth. Forced expiratory pressure is capable of preventing this phenomenon. Emetics act (i) directly upon the vomiting center (as, for instance, apomorphin) . Central vomiting ceases after destruction of the corpora quadrigemina, or division of the anterior columns of the spinal cord or destruction of all the spinal sympa- thetic fibers that pass to the stomach. (2) Other emetics act upon the vomiting center through reflex influences from the stomach or the intestine (copper sulphate, tartar emetic). The irritation reaches the gastric musculature through the pneu- mogastric nerves. (3) Both of these modes of action may be combined. Emetics may also remove mucus from the respiratory organs. It would appear that emetics exert a favorable influence upon the respiratory movements, through irritation of the respiratory center, as, for instance, in small children. THE MOVEMENTS OF THE INTESTINES. For observing the peristaltic movements in animals, the abdominal cavity is opened under a 0.9 per cent, sodium-chlorid solution at blood-temperature in order to avoid the entrance of air ; or the observations may be made through the shaved and uninjured abdominal walls. THE EVACUATION OF FECES. 283 The small intestine exhibits peristaltic movements in a classical manner. The progressive constriction of the canal, which forces the contents before it, always passes from above downward. After death and on exposure of the coils of intestine to the air, peristalsis is often seen to develop in several parts of the intestine at the same time, and as a result the intestinal loops acquire the appearance of a mass of crawling worms. In addition to these movements, pendulum-like movements of the intestine also occur, by which the contents are moved some distance first in one direction and then in the other. The advance of new intestinal contents and the resulting increased distention of the tube due to solid contents or gas causes renewed movement. The large intestine exhibits less active and less extensive move- ments. When the abdominal walls are thin, or in the sac of a hernia, peristalsis may be felt and even seen. Herbivora exhibit more active peristalsis than carnivora. Perhaps the transmission of peristalsis takes place directly through the musculature, as in the heart and the ureter. The ileo-cecal valve, as a rule, does not permit the usually more con- sistent contents of the large intestine to pass back into the small intes- tine. During sleep, at night, the movements of the stomach and the intestines cease. If fluid material is gradually introduced into the rectum from a height of one meter of water-pressure through an intestinal tube, it may pass upward through the ileo-cecal valve into the small intestine, and, with great care, it may reach the stomach and esophagus, and even escape from the mouth and nose. In this way the entire intestinal tract in the living subject can be irrigated, and with cura- tive results ; as, for instance, in cases of cholera (i or 2 per cent, solution of tannic acid in 7.5 per cent, solution of sodium chlorid). Eight or nine liters are sufficient to fill the entire alimentary canal. A crystal of sodium chlorid applied externally to the intestine causes con- traction at that point, with upward peristalsis, while potassium chlorid induces only local contraction. Particles saturated with sodium-chlorid solution and in- troduced into the rectum are carried upward, in part even to the stomach, through the mediation 'of nervous irritation, perhaps of the muscularis mucosae. Pathological. -If an inflammatory or catarrhal condition of the intestinal mucous membrane develops rapidly in consequence of an acute inflammatory irritation, contractions of the inflamed portion, at first marked, occur in the full intestine. When the affected portion has been emptied the movements are no longer more marked than normal. If further contents reach the inflamed portion, the peristaltic downward movement takes place more rapidly than normal and diarrhea results. At times a greatly contracted piece of the intestine is pushed into a neighboring portion (invagination, intussusception). Reduction in the bodily temperature is followed by a decrease in the peristalsis. That antiperistalsis, that is a movement upward toward the stomach, occurs was formerly considered proved by the appearance of fecal vomiting in connection with intestinal obstruction due to stenosis in human beings with occlusion of the bowel. The investigations of Nothnagel, however, throw doubt upon this con- clusion, as he failed to observe effective antiperistalsis after artificial occlusion of the bowel. The fecal odor of the vomited matter may also depend upon its pro- longed sojourn in the duodenum, whence, as the well-known bilious vomiting shows, ingesta may be returned into the stomach. THE EVACUATION OF FECES (DEFECATION). The contents of the intestine remain in the small intestine about three hours, and for a further twelve hours in the large intestine, where they become inspissated, and in the lower portion formed into the fecal mass. Through the peristaltic movement, the feces are forced onward to a point somewhat above that portion of the rectum which 284 THE EVACUATION OF FECES. is surrounded by both sphincter-muscles, of which the upper or internal is formed of unstriated and the external of striated muscle-fibers. Immediately after the act of defecation the external sphincter (Fig. 1 08, S; Fig. 109) usually contracts, and remains contracted for some time. When the muscle relaxes, the elasticity of the parts surrounding the anal opening, particularly of both the sphincter-muscles, is sufficient to insure closure of the anus. In the interval of rest or until the pressure of the feces again occurs, there is no evidence of a permanent contrac- tion (tonic innervation) of the anal sphincters. As long as the fecal matters lie above the rectum, they give rise to no conscious sensation. FIG. 108. The Perineum and its Muscles: i, anus; 2, coccyx; 3, ischial tuberosity; 4, tuberososacral ligament; 5, acetabulum; B, bulbocavernosus muscle; Ts, superficial transverse perineal muscle; F, fascia of the deep transverse perineal muscle; J, ischiocavernosus muscle; O, internal obturator muscle; S, external sphincter ani muscle; L, levator ani muscle; P, pyriformis muscle. It is only their descent into the rectum that causes the feeling of tenesmus. At the same time the stimulation of the sensory nerves of the rectum causes reflex stimulation of the sphincters. The center for this reflex (Budge's anospinal center) is situated in the lumbar cord. In animals, after division of the spinal cord above this center, the anal opening closes actively when touched ; but soon after this reflex contraction the sphincters relax, and the anus may thus remain open for a time. This is due to the fact that the active voluntary contraction of the external sphincter-muscle, already mentioned, under the control of the will (cerebrum), which keeps the anus closed for some time after each evacuation of the bowel, is absent. In dogs, in THE EVACUATION OF FECES. 285 which the posterior roots of the lower lumbar and the sacral nerves were divided, Landois observed that, while recovery was otherwise normal, the anus remained open. Not rarely a portion of the fecal mass protruded for a considerable time, as the sensibility in the rectum and anus was lost in such animals. Neither was reflex contraction of the sphincters possible, nor could voluntary closure of the anus, induced by the sense of feeling alone, take place, although this would other- wise have doubtless been possible. An excitomotor as well as an inhibitomotor influence may be exerted upon the external anal sphincter, as upon any voluntary muscle, from the cerebrum. Nevertheless, closure can be maintained only for a certain time if the pressure from above is considerable. Finally ener- getic peristalsis overcomes even the strongest voluntary stimulation. FIG. 109. The Levator Ani and External Sphincter Ani Muscles. The evacuation of feces, which takes place habitually in human be- ings at a definite interval, once or twice daily, rarely oftener, begins with active peristalsis in the large intestine which passes downward to the rectum. In order that the sphincter muscles may not be excited to reflex activity by the advancing column of feces, it appears that an inhibitory center for the sphincter-reflex, capable of voluntary stimula- tion, must become active. This is situated in the brain (Masius poses in the optic thalamus), whence its fibers pass through the cere- bral peduncles to the anospinal center. During stimulation of inhibitory apparatus, the column of feces passes through t without causing its reflex closure. 286 NERVOUS INFLUENCES AFFECTING INTESTINAL MOVEMENTS. The active peristalsis necessary to cause defecation may be favored and to a certain extent excited, partly by pressure, partly by short voluntary movements of the external sphincter and the levator ani muscles, whereby the my enteric plexus of the lower portion of the large intestine is stimulated mechanically, with the result that active peris- taltic movements of the large intestine are soon set up. The expulsion of feces is favored by active, voluntary abdominal pressure, principally with inspiratory depression of the diaphragm. The soft parts of the pelvic floor are forced downward conically with a strong effort at stool, whereby the anal mucous membrane, which coincidently becomes filled with venous blood, is at times everted. It is the function of the levator ani muscle (Figs. 108 and 109) voluntarily to elevate the soft parts forming the pelvic floor and thus, in elevating the anus, in a measure to slide it over the descending column of feces. At the same time it prevents relaxation of the soft parts of the pelvic floor, particularly the pelvic fascia. As the fibers of both levator ani muscles converge down- ward, and mix with those of the external anal sphincter, they coinci- dently aid the sphincter when energetic contraction takes place, as they bear approximately the same relation to the anus that the strings of a tobacco-pouch bear to its opening. When the desire for stool is marked the closure of the anus can be made more secure by pressure from without through forcible rotation of the thighs outward and the action of the gluteal muscles. During the normal interval between evacuations of the bowel, the feces appear to descend only to the lower extremity of the sigmoid flexure. From this point to the anus the rectum normally is usually free from feces. The strong circular fibers of the muscularis, which Nelaton termed the third anal sphincter, appear, by their contraction, to arrest the further advance of the fecal matter. NERVOUS INFLUENCES AFFECTING THE INTESTINAL MOVE- MENTS. The automatic center for the movements of the intestinal canal is the greatly developed myenteric plexus, which is embedded between the longitudinal and circular layers of the muscular coat. It is this that is responsible for the movements that continue for some time in an excised portion of intestine, just as they occur in the heart. This plexus, constituted mainly of non-medullated nerves, distributes fibers that, after again forming a network, pass to the unstriated muscle-fibers. The cells of the plexus possess an axis-cylinder process and several protoplasmic pro- cesses. Nerve-fibers pass through the mass of ganglia, while others surround the ganglion-cells with their extremities. Special nerve - plexuses, containing ganglia, are found upon the blood-vessels and lymph- vessels of the intestinal wall. When this center is free from all stimulation, the intestine remains in a state of rest, resembling the apnea that occurs with absence of stimu- lation of the medulla oblongata. This occurs during intra-uterine life, as it does also with respect to respiration, in consequence of the large amount of oxygen in the fetal blood. This condition may be termed intestinal rest aperistalsis. It is observed also during sleep, perhaps in consequence of the greater amount of oxygen in the blood. The circulation through the intestinal vessels of blood containing NERVOUS INFLUENCES AFFECTING INTESTINAL MOVEMENTS. 287 the usual amount of gases gives rise to the quiet peristaltic movement of the healthy individual euperistalsis. All stimuli transmitted to the my enteric plexus increase peristalsis, which finally may progress to violent movement, with rumbling in the intestines (borborygmus), and may even cause involuntary discharge of feces and spasmodic contraction of the intestinal musculature. This condition, which corresponds to dyspnea, may be designated dysper- istalsis. This condition may be caused (a) by interruption of the circulation in the intestines, ft matters not whether anemia, as after compression of the aorta, or venous hyperemia is thereby induced. The exciting agent here is the deficiency of oxygen, or the excess of carbon dioxid. Even slighter circulatory disturbances in the intestinal blood-vessels, as, for instance, venous stasis in connection with abundant transfusion into the veins, whereby transitory overdistention of the venous system, and therefore stasis in the portal system occurs, give rise to in- creased peristalsis. This takes the form of noises and rumbling in the intestines, together with involuntary defecation, if, in consequence of transfusion of hetero- geneous blood, stasis becomes marked, as a result of thrombosis of the intestinal blood-vessels. Landois explains in this way the irresistible inclination to stool and the increased peristalsis that attend certain forms of cardiac weakness of acute onset and sclerosis of the coronary arteries, in consequence of which the circulation in the intestines suddenly ceases. A similar state of affairs is observed even under normal conditions. Landois believed that the persistent pressure in constipated individuals induces the evacuation that eventually takes place, as much by exciting peristalsis through the venous stasis in the intestines as by mechanical pressure upon the intestinal canal. Also the increased peristalsis that constantly attends approaching death depends, undoubtedly, upon circulatory disturbances and thus upon an alteration in the amount of gases in the blood in the intestines. The same statement is applicable to the increased intestinal movement that attends certain emotional disturbances, as, for instance, fear. Here the stimulation of the brain passes through the medulla oblongata (containing the center for the vasomotor nerves) to the intestinal nerves and causes circulatory disturbances in the intestines (coincidently with pallor). Restoration of the normal circulatory condition restores the intestines to quiet peristalsis. Salvioli caused blood to flow artificially through excised pieces of intestine by means of cannulas intro- duced into the blood-vessels, and found that blood rich in oxygen caused intestinal rest, while interruption of the circulation caused contractions of the intestines. B6kai was able to overcome the dysperistalsis induced by the introduction of carbon dioxid into the intestines by introducing oxygen into the intestinal cavity. (6) Direct irritation of the intestine causes movement not only of the part directly affected, but also of the neighboring part of the intestines, especially that lying toward the pylorus. The cumulative effect of stimuli is shown here ; that is feeble stimuli, which are too weak to excite movement when applied but once, do so on persistent repetition, as exposure of the intestines to the air, in more marked degree in the presence of carbon dioxid and chlorin, the introduction of certain irritating substances into the intestine, marked distention of the intestinal canal, especially with coincident difficulty in or obstruction to defecation (which occurs frequently in human beings), or direct irritation of different kinds, also inflammatory processes involving the intestine either from within or from without. In this connection, the observation is of interest that induced currents applied to a hernial sac containing intestine excite active peristalsis in the hernia. Local irritation of a portion of the intestine with a tetanizing induced current causes a circular constriction, which advances especially toward the stomach when the current is of considerable strength. The shortening of the longitudinal fibers that are stimulated at the same time extends in both directions. With increasing temperature intestinal rest first results from irritation of the splanchnic nerves; when the temperature reaches 43 C. intestinal movement is resumed. All persistent stimuli of moderate strength cause cessation of dys- peristaltic intestinal movement from overstimulation. This condition may be designated intestinal exhaustion or intestinal paresis. 288 NERVOUS INFLUENCES AFFECTING INTESTINAL MOVEMENTS. This state of rest of the intestine is thus widely different from that attending the condition of aperistalsis. Persistent stasis of blood in the intestinal vessels leads finally to intestinal exhaustion, as, for instance, when thrombosis occurs in the intestinal vessels after transfusion of blood from a different species. Distention of the vessels with indifferent fluids, after compression of the aorta had previously excited active peristalsis, likewise causes cessation of peristaltic movement. In the same category belongs also the condition of rest noted after the temperature of the intestine has been reduced to 19 C. Severe intestinal inflammation also has a similar effect. Under favorable conditions the intestine may recover from this stage of exhaustion after the irritation has ceased. This takes place, as a rule, through a transitional stage attended with active peristalsis. Thus the intro- duction of arterial blood into the vessels of the exhausted intestine causes at first active peristaltic movements, followed by normal peristalsis. The continuous application of strong stimuli finally causes complete paralysis of the intestine in human beings as seen after inflammations, traumatisms, incarcerations, and the like. The intestine becomes greatly distended, as the paralyzed muscularis is no longer able to offer any resistance to the gases expanded by the heat (meteorism). The Peripheral Intestinal Nerves. Of the nerves passing to the intestine the pneumogastric nerve increases the movements of the small intestine and the upper portion of the large intestine, either by conveying the stimuli applied to it to the myenteric plexus, or by causing contractions of the stomach, which, in turn, as true mechanical impulses, excite the intestine to movement. The pneumogastric nerves also contain several inhibitomotor fibers. The splanchnic nerve -the greater derived from the sixth to the ninth, and the lesser from the tenth and eleventh dorsal ganglia is (i) the inhibitory nerve for the intestinal movements, but only so long as the blood in the capillaries has not become venous while the circulation in the intestine remains undisturbed. If the latter condition has arisen, irritation of the splanchnic causes increased peristalsis. If arterial blood be introduced, the inhibitory action is prolonged. Irritation of the origin of the splanchnic nerve in the dorsal cord also produces the inhibitory effect under analogous circumstances, even in the presence of irritation of the spinal cord as a result of strychnin-poisoning, with the occurrence of general tetanic convulsions. O. Nasse believes that it may be concluded from the experi- ments that, in addition to these readily exhausted inhibitory fibers, paralyzed by venosity of the blood, there are present (2) motor fibers that are excitable for a longer time, inasmuch as stimulation of the splanchnic nerve after death always causes peristalsis of the stomach and intestines, as does stimulation of the pneu- mogastric nerve. (3) The splanchnic nerve is also the vasomotor nerve of all of the arteries and veins of the intestines, including the portal vein, thus controlling the largest vascular area of the body. Stimulation of the splanchnic nerve causes contraction, its division dilatation, of all of the intestinal blood-vessels possessing muscle-fibers. In the latter event an enormous accumulation of blood takes place in the intestinal vessels, so that anemia of other parts of the body results, and in consequence even death may take place from anemia of the medulla oblon- gata. (4) The splanchnic nerve is, finally, the sensory nerve of the intestines, and, as such, it is extremely sensitive. Almost all the cells of the solar plexus are included in the course of the fibers of the splanchnic nerve. Nicotin paralyzes these cells, while the peripheral fiber retains its irritability. Stimulation of the nervi erigentes causes contraction of the longitudinal mus- cular fibers and relaxation of the circular fibers of the rectum; while irritation of the hypogastric nerves has the opposite effect according to Fellner. Stimulation of the sigmoid gyrus on the cerebral cortex of the dog, as well as of parts lateral to and behind it, excites intestinal movements through the pneumogastric nerves, as does likewise stimulation of the optic thalamus. Inhibi- tory fibers pass from both of these situations through the spinal cord, from which they make their exit near the middle of the dorsal cord. The drugs that affect the intestine are (i) those that diminish the irritability of the myenteric plexus, and thus decrease peristalsis, even to the point of intes- tinal rest, like belladonna; (2) those that stimulate the nerves inhibiting peris- talsis, and paralyze in large doses, like opium or morphin. The drugs of these two classes cause constipation. Elevation of temperature (also during fever) THE STRUCTURE OF THE GASTRIC MUCOUS MEMBRANE. 289 diminishes intestinal peristalsis through irritation of the splanchnic nerve. (3) Other drugs stimulate the motor apparatus; such as nicotin, to the point of intestinal cramps, muscarin, caffein and some laxatives, which thus act as evacu- ants. The movement excited by muscarin can be neutralized by atropin. As, in consequence of the rapid movement of the intestinal contents, the contained fluid can be absorbed in but small measure, the frequent evacuations that follow are at the same time liquid. (4) Among purgatives, mention should be made of those that irritate the intestines directly, such as colocynth and croton-oil. It is supposed that agents of this kind cause a watery transudation from the blood- vessels into the intestine, just as croton-oil also causes vesicles on the external skin. (5) Certain laxative salts, sodium sulphate, magnesium sulphate and others, liquefy the intestinal contents by retaining for their solution in the intestine the water of the intestinal contents; if, therefore, they are injected into the blood- vessels of an animal, constipation may even result. (6) Calomel (mercurous chlorid) restricts the absorptive power of the walls of the intestine, and also putrefactive decomposition in the bowels. Therefore the fecal evacuations are thin, with little odor, and of a greenish color from admixture of unchanged bili- verdin. THE STRUCTURE OF THE GASTRIC MUCOUS MEMBRANE. The surface of the mucous membrane of the stomach exhibits numerous small depressions, the gastric crypts (foveolae gastricae, Fig. no), lined by a single layer of mucous goblet cells (Fig. 112, d). These cells are sharply delimited at the cardiac orifice from the stratified squamous epithelium of the esophagus; and at the pyloric extremity from the true cylindrical epithelium of the duodenum. The cells with almost homogeneous contents are provided with elliptical nuclei containing nucleoli. Between their narrowed, lower ends are scattered oblong or spindle-shaped, unencapsulated, nucleated elements, exhibiting mitosis, which are intended to replace desquamated cells. All cells are completely open upon their free surface, so that nothing prevents the escape of the mucus elaborated by mucous metamorposis from the cell-protoplasm. The simple tubular gastric glands, generally several in num- ber, empty into the bottom of the gastric crypts. They occur in two different forms : 1 . As true gastric glands, peptic glands of the fundus (Fig. 114), which number about five millions, the largest being present in the fundus. The structureless membrana propria of simple tubular form, has, on its internal surface, two different kinds of cells : (a) the chief cells (Fig. in, II, a), the adelomorphous ceils of Rollett; small, unencapsulated, nucleated, ^pale cells lying close together, lining the inner lumen of the glands, and (b) larger, mainly scattered, plainly projecting parie- tal cells (Fig. in, II, h), the delomorphous cells of Rollett, ovoid or crescentic, without a membrane, darkly granular, readily stained with osmic acid and aniline-blue, containing, at times, several nuclei. They cause bulbous projections of the mem- brana propria. In human beings the parietal cells are thought to reach to the lumen of the spaces within the gland. They are even found scattered under the epithelium of the crypts and the surface of the mucous membrane, as well as i isolated pyloric glands. Between the chief cells secretory spaces are present, and likewise between neighboring parietal cells, while, at the same time, with the latter delicate branching and anastomosing passages in part lead from the excrete duct of the gland into the interior of the parietal cells and in part form a network surrounding them. 2. Only in the vicinity of the pylorus, where the mucous membrane has a FIG. no. Sectional View of the Gastric Mucous Membrane, Showing the Crater-like Depres- sions of the Gastric Crypts: a, a, the most prominent projections of the mucous mem- brane (from a dog). 2QO THE STRUCTURE OF THE GASTRIC MUCOUS MEMBRANE. rather yellowish- white appearance, are the pyloric glands (Fig. 112, A) found, in general in smaller number. At their lower extremity their ducts are not rarely divided into two or more blind sacs. Their cellular contents consist, as a rule, FIG. in. I. Transverse Section through the Duct of a Fundus-gland : a. membrana propria; b, goblet-cells; c, reticular connective tissue. II. Sect-ion through the Glands of the Fundus: a, chief cells; h, parietal cells; r, reticular tissue of the mucous membrane between the glandular tubules; c, divided blood-vessels. FIG. 112.- Isolated goblet-cells; A, pyloric gland of the stomach. FIG. 113. M, Portion of a gastric gland with chief cells (h h) and parietal cells (b b); the latter exhibit intracellular secretory canals. Between the chief cells intercellular secretory ducts (z z) penetrate for some distance; a, excretory duct of the gland. THE STRUCTURE OF THE GASTRIC MUCOUS MEMBRANE. Ce " 8 ' 291 The scanty supporting structure of the gastric mucous membrane consists of reticular -connective tissue with leukocytes, mixed with fibrillary connective tissue and elastic fibers. The mucous membrane possesses a special muscular layer the musculans nrncosae This passes as a rather thick stratum under the base of the gland, often exhibiting an inner circular and an outer longitudinal layer From FIG. 114. Vertical Section through the Gastric Mucous Membrane: g g, the crypts of the surface; p, the mouths of the peptic tubules (fundus glands) with parietal cells (x) and chief cells (y); a v c c , artery, vein and capil- laries of the mucous membrane; i, capillary network for the passage of the mouth of the gland-duct; d d, the lymphatic vessels of the mucous membrane, passing over, at e, into a large trunk (semidiagrammatic representation). this stratum a number of bundles of fibers pass upward between the glands and around them. They appear to be intended for active evacuation of the glandular tubules. Numerous blood-vessels (Fig. 114) enter from the fibrillary connective tissue of the submucosa (a) , spread out into a longitudinal capillary network (c c) between the glands, and reach the free surface, where they again form a fine meshwork (i i) just under the epithelium, and through the meshes of which the mouths of the ducts (g) make their appearance. Collecting at this point the veins unite in the submucosa to form trunks of considerable size (v). 292 THE GASTRIC JUICE. The lymphatic vessels of the gastric mucous membrane begin rather close beneath the epithelium as bulbous or loop-like formations (d d) , then pass per- pendicularly to the submucosa, where they attain a considerable size (e) through the union of adjacent branches. The nerves are the same as those of the intestine. The submucosa consists of bundles of connective tissue with elastic fibers and embedded fat-cells. THE GASTRIC JUICE. The gastric juice is a fairly clear, colorless, levorotatory, readily filtered fluid, with a strongly acid reaction, an acid taste and a character- istic odor. From the presence of free hydrochloric acid, it counteracts putrefaction and, in part, fermentation. Its specific gravity, when the stomach is empty (fasting), ranges between 1004 and 1006.5; after the ingestion of food, from 1010 to 1020, and more than 1020 when the production of acid is diminished. Its amount was said by Beaumont, in 1843, from observations upon a human being with a gastric fistula, to be only 180 grams daily. According to Griinewald, in 1853, it was estimated in a similar case to be 26.4 per cent, of the body- weight in twenty-four hours. Finally it was placed by Bidder and Carl Schmidt, after comparative observations upon dogs, as 6| kilograms in the day, corresponding to y-Q of the body-weight. The gastric juice contains : 1. Pepsin, the characteristic, nitrogenous, hydrolytic ferment or enzyme that dissolves proteids: from 0.41 to 1.17 per cent. 2. Hydrochloric acid occurs free in the gastric juice: from 0.2 to 0.3 per cent. 3. Lactic acid may also be found, either from fermentation of carbo- hydrates (fermentation lactic acid) or from being dissolved out of the meat of the food (sarcolactic acid). Reactions. Hydrochloric acid alone, and in the free state, is identified by Gunzburg's reagent: To a few drops of filtered gastric juice an equal number of drops of a solution of 2 grams of phloroglucin and i gram of vanillin in 30 grams of alcohol are added, and the mixture is evaporated in a porcelain dish over the water-bath, with the development of a rose-red color. Resorcin, 2.5 grams, dis- solved in 50 grams of dilute alcohol, with addition of 1.5 grams of cane-sugar, may be employed in a manner analogous to the foregoing reagent, likewise giving rise to a red color. Reaction for Lactic Acid. A freshly prepared blue mixture of 10 cu. cm. of a 4 per cent, solution of carbolic acid, with 20 cu. cm. of distilled water and one drop of ferric chlorid, is colored yellow by lactic acid. To 5 cu. cm. of the gastric juice to be tested i or 2 drops of hydrochloric acid are added, and the mixture is evaporated over a free flame to the thickness of sirup. The residue is extracted with a little ether, is then poured into a reagent glass containing 5 cu. cm. of water, one drop of a 5 per cent, solution of ferric chlorid is added, and the mixture is shaken. A greenish-yellow color appears even when i part of lactic acid in 1000 is present. The gastric contents, evaporated to the consistency of sirup, to expel the alcohol, are extracted by shaking with ether. The filtrate, on addition of an alcoholic solution of iodin and being heated, yields iodoform, in consequence of the formation of acetaldehyd from the lactic acid. Hydrochloric acid and organic acids together yield the following reactions. To demonstrate the total free acids (those not combined with albumin), Congo- red is used, also in the form of reagent-paper. It indicates the presence of free hydrochloric acid or a considerable amount of free organic acids by becoming blue in color. The same information is afforded by dark-red benzopurpurin, which is changed to a violet color, and also by tropaeolin OO. A little of a concentrated alcoholic solution of the latter, heated with 4 drops of gastric juice in a dish, yields a bluish-violet stain. THE SECRETION OF THE GASTRIC JUICE. 293 4. For a consideration of the milk-ferment, reference may be made to page 300. 5. The large amount of mucus adherent to the surface of the mucosa is a secretion of the mucous goblet-cells. 6. Inorganic matters are present in percentages for human beings (and for dogs, in parenthesis) as follows: Water, 994.40 (973.06); hydro- chloric acid, 0.20 (2.84); calcium chlorid, 0.06 (0.96); sodium chlorid, 1.46^(2.82); potassium chlorid, 0.55 (1.09); ammonium chlorid (0.5); calcium, magnesium, and iron phosphates, 0.125 (2.7). Organic matters, principally pepsin, are present to the amount of 0.32 per cent. (1.71). Of foreign substances, the following appear in the gastric juice after introduction into the body: potassium sulphocyanid, iron lactate, potassium ferrocyanid, sugar, etc. Ammonium carbonate is found in the presence of uremia. THE SECRETION OF THE GASTRIC JUICE. During the course of digestion characteristic changes take place in the chief cells, and in the parietal cells of the fundus glands and in the cells of the pyloric glands. The chief cells contain granules that are consumed during the process of secretion. The granules contain the pepsin-forming substance, which is transformed into pepsin. The size of the chief cells diminishes also during secretion. At rest these cells take from the lymph, material for the production of the granules. The parietal cells, during the period of secretion, appear first to be swollen, then to become smaller. All of the cells, further, are darker, and the nucleus of the cells of the pyloric glands moves toward the center. The secretory ducts become more distended. In some animals the chief cells, during secretion, bear a fringe of short, hair-like processes (Tornier's "brush-fringe"!), directed toward the lumen of the gland. The pepsin is formed in the chief cells. If these are swollen, they produce much pepsin; if shrunken, they produce but little. The pyloric glands also secrete pepsin, though in much less amount. During the first stage of hunger the pepsin accumulates; while during the period of digestive activity it is eliminated, as it is also when hunger is pro- tracted. Klemensiewicz removed the pyloric portion of the stomach of a dog with two incisions; sutured the duodenum to the stomach, and allowed the pyloric portion, still in communication with its blood-vessels, to heal in the abdominal wound, after closure of its lower extremity by sutures. The secretion of this portion of the stomach was viscid and alkaline, containing 2 per cent, of solid matters, including pepsin. The glands themselves contain no pepsin, but only a zymogen, namely, the pepsinogenic substance or propepsin, which occurs in the granules of the chief cells. The zymogen, of itself, exerts no influ- ence upon proteids. If, however, it be treated with hydrochloric acid or sodium chlorid, it is transformed into pepsin. In addition to pepsin, the pepsinogenic substance may be extracted from the mucous membrane of the stomach by means of water free from acid. The milk-ferment also originates in the chief cells. The hydrochloric acid is formed by the parietal cells. It is found 294 THE SECRETION OF THE GASTRIC JUICE. on the free surface of the mucous membrane, as well as in the excretory ducts of the gastric glands. In the depth of the glandular tubules, however, the reaction is generally alkaline. The acid must, therefore, be advanced rapidly from the depth to the surface. Sarcolactic acid can be rapidly extracted as such from the chyme. For the production of lactic acid through fermentation in the stomach it is necessary that the carbohydrates have been present for a consider- able time. This does not occur in the healthy individual, but in asso- ciation with great diminution in the production of hydrochloric acid, stagnation of the ingesta in the stomach, and interference with gastric absorption, particularly in the presence of gastric carcinoma. Lactic-acid bacteria are always present in the stomach, though they exhibit no activity in the presence of healthy gastric juice on account of the anti-fermenta- tive influence of the hydrochloric acid. Lactic acid develops, however, only in the absence of free hydrochloric acid, which is particularly often the case in the presence of gastric carcinoma. The hydrochloric acid first secreted at once combines in the stomach with the proteids to form acid albumin ates. These do not yield the color-reactions of free acid. As the secretion progresses free hydro- chloric acid makes its appearance. If the secretion of gastric juice be enfeebled it may, therefore, happen that the production of hydrochloric acid is not sufficient to permit of the appearance of free hydrochloric acid. When the tests for hydrochloric acid in the stomach-contents are distinctly, even though feebly, positive, sufficient hydrochloric acid is present; an unusually strong reaction is indicative of abnormally increased production. If the reaction is wanting, a decinormal hydrochloric-acid solution is added to a measured amount of gastric contents until a distinct reaction is obtained by Giinzburg's test. The amount of hydrochloric acid consumed is then proportional to the degree of the hydrochloric-acid insufficiency present. In regard to the production of free acid, the following appears to be established. The parietal cells secrete hydrochloric acid from the chlorids that the mucous membrane takes up from the blood. There- fore, the production of hydrochloric acid ceases when the chlorids are withdrawn from the food, as well as in the state of hunger. The active agent in this connection has not been discovered; yet it is established that, if carbon dioxid acts continuously on the chlorids, nevertheless, hydrochloric acid is expelled by the much weaker carbon dioxid. Maly and others assume that the production of hydrochloric acid takes place within the parietal cells as follows : 2Na 2 HPO 4 +3CaCl 2 =Ca 3 (PO 4 ) 2 + 4 NaCl-f2HCl. The bases set free by the separation of the hydrochloric acid are excreted in the urine, with the development of a slightly acid reaction. When the stomach is empty the gastric juice contains some hydro- chloric acid, but a more abundant secretion is, according to Pawlow, brought about in a most striking manner by the appetite, and also by the stimulation of the food under natural conditions, as well as by water, meat-extractives, and even by indigestible matters when intro- duced into the stomach. Under these circumstances the mucous mem- brane is reddened from increased activity of the circulation, so that the outflowing venous blood is lighter in color. The excitation of the secre- tion is a reflex process. The sensory nerves of the pharynx and the METHODS OF OBTAINING THE GASTRIC JUICE. 295 stomach excite, in a centripetal direction, the medulla oblongata which contains the center for this reflex. The centrifugal path to the mucous membrane traverses the pneumogastric nerves, after the division of which the reflex is abolished. The mucous membrane subsequently furnishes a moderate amount of a feebly active, paralytic secretion. During sleep in the stage of digestion, the amount of acid increases. Heidenhain found in experiments upon dogs in which, in the same way as the pylorus, he isolated the fundus for the formation of a blind sac that mechan- ical irritation induced only local secretion. If, however, absorption of digested substances took place at the point of irritation, the secretion spread out over a larger surface. Small quantities of alcohol, introduced into the stomach, increase the secretion Of the gastric juice, while large amounts abolish it and enfeeble the movements ot the stomach. Fat inhibits the secretion of the gastric juice. Artificial digestion is somewhat disturbed by alcohol up to 2 per cent., and in greater degree by 10 per cent, alcohol; 20 per cent, alcohol retards, while still larger amounts abolish it. Beer and wine retard digestion, and undiluted they prevent artificial diges- tion. The administration of large amounts of sodium chlorid diminishes the secre- tion of hydrochloric acid, while the ingestion of much sugar only delays it After two days of fasting the secretion of hydrochloric acid ceases (in the dog). Gastric ulcers cause reflex increase in the production of hydrochloric acid; jaundice, nervous gastric affections and anemias, a reflex diminution. The gastric juice, which passes into the duodenum after digestion is completed, is neutralized by the alkalis of the intestinal and of the pancreatic juices. The pepsin is absorbed as such, and can be found in small amounts in the urine and in the muscle-juice. If the gastric juice is removed completely through a gastric fistula, the alkalies in the intestines become so abundant that the urine is ren- dered alkaline. The acid gastric juice in the new-born is quite intensely active. It most readily digests casein, and next in order fibrin and other proteids. In consequence of excessive acidity of the gastric juice, large masses of casein, difficult of digestion, form in the stomach of infants, and are especially tough after the ingestion of cow's milk. The following drugs are excreted by the gastric juice after introduction into the body-juices: Morphin, veratrin, caffein, quinin, antipyrin, chloroform, chloral hydrate, methyl-alcohol, ethyl-alcohol and acetone. Comparative. According to Klug, the parietal cells of grain-eating birds pre- pare also pepsin, in addition to hydrochloric acid. The gastric glands of the frog, which possess only parietal cells, likewise secrete pepsin; the pyloric glands of the dog, which contain only chief cells, nevertheless secrete acid. Accordingly both kinds of cells secrete hydrochloric acid. METHODS OF OBTAINING THE GASTRIC JUICE. THE PREPARATION OF ARTIFICIAL DIGESTIVE FLUIDS; DEMONSTRA- TION AND PROPERTIES OF PEPSIN. To obtain the gastric juice Spallanzani had fasting dogs swallow bits of sponge enclosed in perforated leaden capsules, and withdrew them after they had become saturated with the gastric juice. In order to prevent admixture with the secre- tions of the mouth, the sponge is best introduced through an opening made in the esophagus ligated above. Beaumont (1825-1833), an American physician, was the first to obtain gastric juice from a human being, in the case of the Canadian hunter, Alexis St. Martin, whose stomach had been opened by a bullet-wound, with the formation of a per- manent gastric fistula. Various substances were introduced directly into the stomach through the opening, and examined from time to time as to their digestion. Guided by this, Bassow, in 1842, was the first to establish an artificial gastric fistula in a dog. The wall of the stomach is opened below the xiphoid process, and the margins of the gastric opening are united by suture to the margins of 296 METHODS OF OBTAINING THE GASTRIC JUICE. the wound in the abdominal walls. A short tube with a terminal plate is placed in the fistula in such a manner that the plate lies in contact with the margin of the mucous membrane. The tube possesses a screw-thread, upon which an appro- priate cannula can be so screwed that the terminal plate lies upon the abdominal wall outside of the margins of the wound. The parts are joined in the following manner H -H. As a rule the opening of the cannula is corked. If in such dogs the excretory ducts of the salivary glands are additionally ligated, unmixed gastric juice is secured. According to C. A. Ewald and Leube, dilute gastric juice can be obtained from human beings by introducing water into the empty stomach through a tube that acts like a siphon, and withdrawing the fluid by siphonage after a short time. An important advance was made by Eberle, in 1834, who taught that artificial gastric juice could be prepared by extracting pepsin from the gastric mucous membrane by means of dilute hydrochloric acid. Dilute hydrochloric acid serves for the extraction of the triturated gastric mucous membrane 0.088 per cent, for the digestion of fibrin, 0.16 per cent, for the digestion of coagulated albumin being added anew, in quantities of a half liter every six or eight hours. The later extracts are even more active than the first. The fluid collected is filtered and in it are placed, at the temperature of the body, the substances to be digested. It is, however, necessary to add more hydrochloric acid from time to time. That degree of acidity affects digestion most ^ favorably that most causes the proteids to swell. According to Klug, gastric juice containing 0.6 per cent, of hydro- chloric acid and o.i per cent, of pepsin is most effective. Pepsin from dogs is especially active. Digestion pursues a favorable course between 37 and 40 C.; while it ceases in the cold, as well as at higher temperatures. The hydrochloric acid employed may be replaced, to a certain extent, by other halogen-acids, whose activity is inversely proportional to their molecular weight ; further by from six to ten times as much lactic acid; by nitric acid; in a much less effective manner, finally, by oxalic, sulphuric, phosphoric, acetic, formic, succinic, tartaric, and citric acids. In general, the acids with greater acidity act more powerfully, with the exception of sulphuric acid. The action of the different acids varies, however, accordingly as fibrin, casein, solid or liquid albumin is employed. v. Wittich showed that pure pepsin can be extracted from the gastric mucous membrane by means of glycerin also. After cleaning the mucous membrane, it is left in alcohol for twenty-four hours, then dried, pulverized and sifted, and then extracted for a week in glycerin. On addition of alcohol to the filtered extract pepsin is precipitated, and this, dissolved in dilute hydrochloric acid, yields active gastric juice. The preparation of perfectly pure pepsin has been effected by W. Kiihne by exposing comminuted pigs' stomachs to autodigestion with dilute hydrochloric acid at the temperature of the body. The mass, which is for the most part liquefied, is saturated with ammonium sulphate, by which pepsin and albumoses still present are precipitated. The residue collected on the filter is again and if necessary repeatedly digested in the incubator, after addition of dilute hydrochloric acid. If, finally, all of the albumin has been converted into peptone, the pepsin alone is precipitated by repeated saturation with ammonium sulphate, and is collected on the filter. It is dissolved in water, its salts are removed by dialysis and it is finally precipitated in a pure state by alcohol. Briicke had previously prepared pure pepsin by causing a voluminous precipitate in the digestive mixture including the pepsin, and separating the latter. Pekelharing found that a strongly active arti- ficial gastric juice, on dialysis with water, caused the separation of a precipitate of pepsin. In all the processes of extraction, the yield of pepsin is greatest when the mucous membrane, protected from putrefaction, is exposed to the air for some time, as subsequently propepsin and pepsin are formed in the gland-cells. Pure pepsin is a colloid substance. It does not yield the reactions of albumin to the following tests: It does not respond to the xantho- proteic test, is not precipitated by acetic acid and potassium ferrocyanid, by tannic acid, mercuric chlorid, argentic nitrate or iodin. In other respects it is to be included among the albuminoid substances. Pepsin, when heated to a temperature of from 55 to 60 C. or above, in acid solution, is rendered inactive. THE PROCESS AND THE PRODUCTS OF GASTRIC DIGESTION. 297 THE PROCESS AND THE PRODUCTS OF GASTRIC DIGESTION. The mixture of finely divided food and gastric juice is designated chyme. Upon this the gastric juice exerts its action. ACTION UPON PROTEIDS. The pepsin and the free hydrochloric acid are capable of transforming the proteids, at the temperature of the body, into a readily soluble modification that has been designated peptone. In this process the proteids are changed first into bodies possessing the character of synto- nins, and in this condition the solid proteids are swollen. Syntonin is an acid-albuminate. By neutralization, with cautious addition of an alkali, the albumin is precipitated. Then, by combination with water and division into numerous small molecules, a product results, which is, to a certain extent, an intermediary body between albumin and peptone the albumose of W. Kuhne and Chittenden (propeptone of Schmidt-Mulheim). This is soluble in water, readily soluble in dilute acids, alkalies and salts. These solutions are not precipitated by boiling, but by acetic acid and potassium ferrocyanid, as well as by acetic acid and saturation with sodium chlorid or magnesium sulphate. Albumose is precipitated by nitric acid, but it is redissolved, with the production of an intense yellow color when heated, and it is again precipitated on cooling. Some albumoses possess diffusibility. With the continued action of the gastric juice, the albumose passes over into soluble and readily diffusible peptone. The unchanged pro- teids behave toward the peptones as anhydrids with a large albumin- molecule. The production of peptone and its solution result, therefore, from decomposition with the taking up of water, brought about by the hydrolytic ferment, pepsin. This action takes place best at the tem- perature of the body. According to W. Kuhne, the proteid molecule contains two different substances, namely hemi-albumin and anti-albumin. By the action on these of hydrochloric acid syntonin is produced. This is next broken up into the two primary albu- moses: protalbumose, soluble in water, and hetero-albumose, soluble in salt- solutions. Both are then transformed into deutero-albumoses, which, in contra- distinction to the primary albumoses, are not precipitated in neutral solution by saturation with sodium chlorid. Deutero-albumose in contradistinction to pro- talbumose is not precipitated by copper sulphate. ^ The deutero-albumoses are then decomposed into peptones : hemipeptone and antipeptone. The pepsin enters into intimate relations with the proteid molecule. The greater the amount of pepsin present, the more rapidly, to a certain degree, does digestion take place. The pepsin itself undergoes almost no change, and if care is taken to keep the amount of hydrochloric acid always the same, it is able to digest new amounts of albumin (one part 'to about 500,000 parts). Nevertheless some pepsin is consumed in the process of digestion. The proteids are introduced into the stomach either in a liquid or in a solid form. Of the liquid proteids only casein is at once coagulated in solid form and precipitated and then redissolved. The other liquid proteids remain liquid, are converted into the condition of syntonms, and then immediately into albumoses and finally into peptones, that is, actually digested. Uncoagulated and coagulated proteids, globulins, fibrin, som 298 THE PROCESS AND THE PRODUCTS OF GASTRIC DIGESTION. of vitellin, chondrigen, collagen, and elastin, though with difficulty, are in the same way converted into albumoses and peptones; while neuro- keratin, keratin, and nuclein remain undigested. During the digestion of albumin, absorption of heat takes place, demonstrable by the thermometer. Accordingly the temperature of the chyme in the stomach falls, in the course of two or three hours, from 0.2 to 0.6 C. The coagulated proteids may be designated the anhydrids of the liquid proteids and the latter in turn the anhydrids of the peptones. Thus the peptones represent the highest possible stage of hydration of the proteid bodies. Peptones may also be obtained from proteids with the aid of such agents as usually cause hydration, particularly by treatment with superheated steam vapor, through the action of strong acids, caustic alkalies, ferments of putrefaction and some other ferments, as well as by ozone. The proteid anhydrids may be reconverted from this stage of hydra- tion by the abstraction of water. By heating with acetic-acid anhydrid at a temperature of 80 C. peptone is transformed into syntonin. Also by heating to a temperature of 170 C., through the action of the galvanic current in the presence of sodium chlorid, and through the action of alcohol together with salts, peptone is retransformed into albumin. Albumose was thus first seen to result from fibrin-peptone. Properties of Peptones. (i) They are readily and completely soluble in water. ( 2 ) They diffuse readily through membranes , more readily than propeptones. (3) They also filter much more readily than albumin through the pores of animal membranes. (4) From a mixture of pep- tone, propeptone, albumin and pepsin, first neutralized and then feebly acidulated with acetic acid, neutral ammonium sulphate added in excess precipitates everything except peptone. (5) Peptones are not precipi- tated by boiling, or by nitric acid, or acetic acid and potassium ferro- cyanid, or by acetic acid or by saturation with sodium chlorid. (6) They are precipitated by phosphotungstic, by phosphomolybdic acid, and by biliary acids; precipitated by tannic acid, they are redissolved in an excess. Other precipitating agents are mercuric chlorid and nitrate, mercuric iodid , potassium iodid . ( 7 ) They yield all of the color-reactions of albumin. (8) With sodium hydrate and copper sulphate in the cold, they give a purple-red color (biuret-reaction). The biuret-reaction is yielded also by propeptone, as well as by a proteid body, the so-called alkophyr, formed coincidently in the process of artificial digestion and soluble in strong alcohol. Gelatin-peptone and gelatin are precipitable by tri- chloracetic acid, while albumin-peptone is redissolved in an excess of this acid. This is a useful means of differentiating these peptones. The peptones of the various proteid bodies are distinguished by the amount of sulphur they contain, with some of which this substance is but* loosely combined, while with others it is firmly united. All have a disagreeable and bitter taste. In order to demonstrate the rapidity with which fibrin is digested by the gastric juice, Grunhagen places in a funnel the fibrin that has been saturated with 0.2 per cent, hydrochloric acid, moistens it with digestive fluid and notes the rapidity with which the fibrin gradually melts away, drop by drop, and finally is entirely dissolved. Grutzner stains the fibrin with carmine, saturates it with o.i per cent, hydrochloric acid, and places it in the digestive fluid. The more rapidly the latter becomes stained uniformly red, in consequence of digestion of the fibrin, the more energetic, naturally, is the digestive action. Quantitative Estimation of the Activity of Pepsin. Of a solution of egg-albumin (3 grams in 160 cu. cm. of 0.4 per cent, hydrochloric acid) two specimens of 10 THE PROCESS AND THE PRODUCTS OF GASTRIC DIGESTION. 299 cu. cm. are taken, 5 cu. cm. of gastric juice being added to the one and 5 cu. cm. of water to the other. The mixtures are poured into Esbach's tubes up to the mark U. Both tubes are then kept for one hour at a temperature of 37 C after which Esbach's reagent is added up to the level of the mark R, and the amount of the precipitate in both tubes is noted after the lapse of twenty-four hours. Pep- tone is not precipitated. Chronic gastric catarrh and carcinoma yield low digestive values, while hypersecretion of the gastric juice may increase the digestive in- tensity. Preparation of Pure Peptone. The diluted digestive solution, freed from albu- minates by boiling, and with an almost neutral reaction, is first saturated, while boiling, with ammonium sulphate, filtered when cool, again heated, after beginning to boil made strongly alkaline by adding ammonia and ammonium carbonate* again saturated in the heat with ammonium sulphate, -filtered after cooling, again heated until the odor of ammonia has disappeared, again saturated with the salt, hot, and acidulated with acetic acid. The fluid, filtered in the cold, contains pure peptone. The peptones are undoubtedly those modifications of proteids that are intended, after absorption from the digestive tract, and later through the blood, to be employed to replace the proteids consumed by the pro- cess of metabolism in the living organism. If much albumin has already been digested by the gastric juice, the pepsin is precipitated and becomes inactive if some hydrochloric acid is not again added from time to time. Admixture with bile in the test-tube impairs the activity of pepsin; nevertheless the entrance of bile into the stomach causes no permanent derangement, as renewed amounts of pepsin are at once secreted by the gastric mucous membrane. The stomach digests less well food that has not been thor- oughly masticated or properly insalivated. The presence of blood or of serum prevents the action of pepsin, as well as of trypsin and of the lab-ferment. Heated to a temperature of 65 C. the pepsin in the gastric juice becomes inactive, pure pepsin even at a temperature of 55 C. Concentrated acids, alum and tannic acid abolish the process of peptic digestion. Alkalinity of the gastric juice, as, for instance, from the presence of large amounts of saliva, also concentrated solution of alkaline salts, such as sodium chlorid, magnesium sulphate and sodium sulphate, have the same effect, as do also sulphurous and arsenous acids, and potassium iodid; while small amounts of sodium chlorid increase the secretion and favorably influence the action of the pepsin. The salts of the heavy metals, which form precipitates with pepsin, peptones and mucin, disturb gastric digestion. According to Langley and Eakins, alkalies rapidly destroy pepsin, and propepsin less rapidly. Acids (as lactic, acetic and hydrochloric) precipitate the gastric mucus and stimu- late the secretion of pepsin, while the salts of the alkalies have exactly the opposite effect. Alcohol precipitates the pepsin, although this is redissolved on addition of water, so that digestion can then proceed again undisturbed. Agents that hinder thorough saturation of proteids, as, for instance, binding them tightly, or concen- trated solutions of astringent salts, retard digestion. The ingestion of half a liter of cool water does not disturb gastric digestion in the healthy individual, though it does when the function of the stomach is de- ranged, while the ingestion of a larger amount impairs the digestive activity of the stomach. The same effect is brought about by strong muscular action. In the horse moderate movement (trotting) assists the digestion of starches in the first hour. Warm compresses over the epigastric region favor gastric digestion According to Penzoldt, the digestibility of various proteid articles of food by the stomach is given in the following order. Easily digestible: boiled brain and thymus, pike, sea-fish, carp, oysters, chicken, boiled pigeon, raw scraped beef or veal, wheat-bread, cauliflower, soft-boiled egg (casein, alkali-albuminate) . Digest ible with moderate ease: boiled beef and veal, duck, goose, pork, salt potatoes, rye- bread, rice, tapioca, asparagus, rape-cole, carrots, raw egg, pur6e of legumes. Digestible with difficulty: salmon, salt fish, highly salted caviare, string beans, hard- boiled egg. The digestibility of the different meats, from the more to the less readily digestible, is as follows: veal, lamb, mutton, pork, beef, rabbit, horse. 3OO ACTION UPON OTHER FOODS. ACTION UPON OTHER FOODS. Milk coagulates in the stomach, with the liberation of heat, as a result of precipitation of the casein, which encloses the fat globules. The free acid of the stomach is alone sufficient for precipitation, the alkali being withdrawn from the casein, which it holds in solution. Hammarsten, in 1872, discovered a special rennet-ferment in the gastric juice, which coagulates the casein in either neutral or alkaline solutions. On this fact depends the preparation of cheese by means of calf's stomach rennet. The rennet is formed in the chief cells of the gastric glands from a rennet-forming substance, by the action of an acid. The rennet-forming substance is present in the mucous membrane in much larger amount than rennet itself. One part of rennet-ferment is capable of precipitating 800,000 parts of casein. The addition of calcium chlorid hastens, while water retards, coagulation. An excess of alkali impairs the activity of rennet. The rennet-ferment is best assisted by hydro- chloric acid, followed, in order, by lactic, acetic, sulphuric and phosphoric acids. The casein, as well as the nucleo-albumin, is converted in the process of diges- tion, mainly into peptone rich in phosphorus; a residue poor in phosphorus, para- nuclein, remaining as an insoluble product. The rennet-ferment is destroyed by long-continued artificial digestion. To obtain rennet, Hammarsten agitates artificial gastric juice prepared from the calf's stomach, and after neutralization, with magnesium carbonate. The filtrate contains only rennet, which, after acidulation with acetic acid, is precipitated by the in- troduction of liquid stearic acid, to which it adheres. The acid is dissolved in ether, which can then be readily separated. Finally, sugar of milk is converted in the gastric juice into lactic acid, by fermentative activity lactic-acid ferment. Further, the milk- sugar in the stomach and intestines is, in part, transformed into grape- sugar. Cane-sugar is gradually converted into grape-sugar, in which process, according to Uffelmann the gastric mucus, according to Leube the gastric acid, plays the most important part. ACTION ON THE DIFFERENT TISSUES AND THEIR CONSTITUENT MATERIALS. ( i) The gelatin-yielding substance of the various supporting structures connec- tive tissue, fibrous cartilage and the matrix of bone as well as glutin itself, is pep- tonized and digested in the gastric juice. (2) The structureless membranes (mem- branae propriae) of the glands, sarcolemma, the nerve-sheath of Schwann, the capsule of the crystalline lens, the elastic layers of the cornea, the membranes of the fat-cells, are likewise digested, but scarcely the elastic, fenestrated membranes and fibers. (3) Striated muscular tissue forms after digestion of the sarcolemma and breaking up of the transversely striated contents into discs and fragments of fibrils, as well as unstriated muscular tissue, a true digested peptone, in consequence of hydration and the decomposition of the myosin. Remains of meat, however, always pass over into the intestine. (4) The proteid elements of the soft cellular structures of the glands, stratified epithelium, endothelium and lymphoid cells, are converted into peptone, while the nuclein of the nuclei cannot, apparently, be digested. (5) The horny portions of the epidermis, nails, hairs, as well as the chitin and the wax of lower animals, are indigestible. (6) The erythrocytes are digested, the hemoglobin decomposed into hematin and a globulin -like substance. The latter is peptonized; the former remains unchanged, and in part appears in the feces, and in part is absorbed and transformed into the coloring-matter of the bile. (7) The fibrin is easily digested into propeptone and fibrin-peptone by the taking up of water and the breaking up of the molecule. Mucin is digested in the stomach. (8) Of vegetable articles of food, vegetable fats are not changed by the gastric juice. The vegetable cells give up their protoplasmic contents for the production of peptone, while the cellulose of the cell-walls is undigestible in the stomach of human beings. THE GASES OF THE STOMACH. 301 That the stomach is also capable of digesting parts of a living body is shown by the fact that the thigh of a living frog or the ear of a rabbit, introduced into a gastric fistula in a dog, will be partly digested. The edges of gastric ulcers and fistulas in human beings are also eroded by the digestive activity of the gastric juice. The question was early asked, Why does the stomach-wall not digest itself? As, after death, the mucous membrane is, in fact, often rapidly softened by autodigestion (gastric softening), the opinion is justified that, so long as the circulation is maintained, the tissues are constantly protected against the action of the acid by the alkalinity of the blood. If the reaction of the gastric juice be alkaline, digestion cannot be inaugurated. Ligation of the blood-vessels of the stomach resulted, according to Pavy's investigations, in digestive softening of the gastric mucous membrane. In human beings morbid occlusion of the vessels causes, in an analogous manner, the development of gastric ulcers. Also the thick, firmly adherent layer of mucus may help to protect the uppermost layer of the mucous membrane against autodigestion. In general, however, the conditions, with respect to all peptonizing ferments, are such that fully living protoplasm, therefore also that of the epithelial cells of the stomach, possesses the property of being able to resist the action of enzymes, as it is capable of decomposing all, even the most complicated, molecules of inanimate substances. Amcebae, bacteria, worms, larvae and embryonal vegetable cells are not affected by artificial digestive juices, not even by trypsin. After extirpation of the stomach, digestion is continued by the pancreas, the liver and the intestines. The stomach is a protective apparatus with respect to the intestine, as it removes various injurious influences, particularly of bacterial origin. THE GASES OF THE STOMACH. The stomach always contains gases, derived in part from air directly swallowed, as, for example, with the saliva, and in part from gases that pass backward from the duodenum. If the larynx and the hyoid bone are suddenly drawn forcibly forward (as in vomiting), a considerable amount of air enters the space behind the larynx and when the latter returns to its position of rest, is carried down by the peristalsis of the esophagus. One can feel distinctly the downward passage of such a quantity of air. At times, even without any movement of deglutition, a number of small air-bubbles enter the stomach. These masses of air constantly undergo change, owing to the absorp- tion of oxygen into, and the elimination of carbon dioxid from, the blood. The rather abundant production of carbon dioxid in the stomach depends, however, on chemical processes resulting from the admixture of the pyloric secretion, containing sodium carbonate, with the secretion of the fundus, containing acid. According to Planer, the amount of oxygen is extremely small, while that of carbon dioxid is considerable. A portion of the carbon dioxid in the saliva is set free by the acid of the gastric juice. The quantity of nitrogen is indifferent. GASES OF THE STOMACH. VOLUMES IN PER CENT. (According to Planer.) HUMAN CADAVER AFTER VEGETABLE DIET. Doc. I. n. I. After a Meat diet. II. After a Diet of Legumes. CO 3 . H N O 20.79 6.71 72.50 33-83 27.58 38.22 o-37 25.2 32-9 68.7 6.1 66.3 0.8 302 STRUCTURE OF THE PANCREAS. Abnormal development of gases, in cases of gastric catarrh, occurs only when the reaction of the gastric contents is neutral. Thus, in the presence of butyric- acid fermentation, hydrogen and carbon dioxid are produced, while acetic-acid and lactic-acid fermentation generate no gases. Marsh-gas (CH 4 ) also is found; though this can reach the stomach only from the intestine, as it can be produced only in the absence of oxygen. Traces of hydrogen sulphid generated by the bacterium coli commune are formed, at times in connection with benign dilatation of the stomach and motor insufficiency. Yeasts and various bacteria are also found in the stomach. STRUCTURE OF THE PANCREAS. The pancreas is a compound tubular gland with terminal alveoli which constitute the chief portions of the gland. On the internal sur- face of the membrana propria, formed of fibrillar tissue, lie the some- what cylindrical-conical secreting cells, which consist of two layers: (i) the smaller, parietal layer, which is transparent, lamellated, stri- ated, and can be deeply stained by carmine, and (2) the internal layer (Bernard's granular layer), which is deeply granular, and stains but slightly. Between the two layers lies the nucleus. During the process of secretion a visible transformation takes place continually in the cell- substance ; the granules in the granular layer undergo solution and form constituents of the secretion, while in the external layer the homo- geneous substance is renewed, and is later again transformed into granu- lar matter. This, in turn, again moves inward toward the lumen of the alveolus. In detail there takes place in the first stage of digestion (from the sixth to the tenth hour) a consumption of the granular inner zone and a growth of the FIG. 115. Changes in the Cells of the Pancreas in the Different Stages ol Activity: i, in the state of hunger; 2, in the first stage of digestion; 3, in the second stage; 4, with paralytic secretion. striated outer zone (Fig. 115, 2). In the second stage (from the tenth to the twentieth hour) the inner zone of the swollen gland has increased greatly in size, while the outer zone is much diminished (Fig. 115, 3). In the state of hunger the latter again increases in size (Fig. 115, i). In the pancreas, yielding a para- lytic secretion, and reduced in size, the inner zone of shrunken cells is almost entirely lost. In consequence of increased secretion, some of the secreting cells undergo a change, so that the acini form irregular collections containing many granules, and have lost all resemblance to glandular acini. Entire cells are also destroyed during the activity of the gland and new ones are again formed. The finest excretory ducts of the acini begin as intercellular secretory spaces. With the alveolus there is connected an intercalary portion, constituted of flat cells, and which develops in the center of every acinus. Then a sort of salivary duct follows, without striated epithelium, as in the salivary glands. From the micro- center of the cells of the excretory-duct system a ciliated flagellum, the "outer thread," projects free into the lumen of the canal. The pancreatic duct, which possesses an axial course and as a rule empties into the dtiodenum in common with the bile-duct, while a smaller branch of the duct makes its entrance at a special papilla at a higher level, consists of an inner, denser, and an outer, looser, wall of connective and elastic tissue, together with THE PANCREATIC JUICE, 303 unstnatcd muscular fibers mainly pursuing a circular course, and lined internally by a single layer of cylindrical epithelium. Small mucous glands lie in the main duct and in its larger branches. Medullated and non-medullated nerves which in their course are connected with ganglia, pass to the glandular acini' but their terminations are unknown. Blood-vessels surround the acini, in part of large size and in abundance in part isolated. The fresh pancreas contains water , albummates ferments, fats and salts. The resting gland contains much leucin isoleucm and tyrosm; further, butalanin, often xanthin and guanhv lactic acid' formic acid, fatty acids; most of these from autodecomposition. THE PANCREATIC JUICE. To obtain the pancreatic juice Regner de Graaf, in 1664, tied in the excretory duct of a dog a cannula provided with an empty bag at its extremity, in which the juice collected Others passed the tube through the abdominal walls exter- nally and thus made a transitory cannula-fistula, which closed in the course of a tew days, with inflammatory expulsion of the extremity of the cannula that had been tied m place. In order to establish a permanent fistula, either a duodenal istula is made, like a gastric fistula, through which the duct of Wirsung is cathe- tenzed by means of a thin tube ; or the duct is opened in a dog and drawn toward the abdominal wound and an attempt is made to unite the wound in the duct with the abdominal wound so as to form a fistula. Heidenhain eliminates the portion of the duodenum in which the duct opens from the continuity of the intestine, incises it, and fixes it outside of the abdominal wound. From such a permanent fistula an abundant, feebly active, watery secretion, rich in sodium carbonate, is collected. From a freshly made opening and before the onset of inflammatory processes, a scanty viscid fluid is obtained which exerts energetic and characteristic physiological actions. Obviously, the scanty, viscid secretion is normal, while the watery, abundant secretion is abnormal and derived from the dilated blood-ves- sels, perhaps in consequence of paralysis of the vasomotor nerves, and as a result of increased transudation. The latter would thus in a cer- tain sense be a paralytic secretion. The amount must vary greatly, accordingly as viscid or watery secretion is produced. During digestion a large dog secreted from i to 1.5 grams of viscid secretion; Bidder and Schmidt obtained from a permanent fistula from 35 to 37 grams of watery secretion in twenty-four hours, for each kilogram of weight. While the resting, inactive gland is flabby, yellowish red in color, the secreting gland is turgescent and reddened from the dilatation of its blood-vessels. Normal pancreatic juice is transparent, colorless and odorless, with a salty taste, and a strongly alkaline reaction from the presence of 0.4 per cent, sodium carbonate, and therefore effervescent from escape of car- bon dioxid on addition of acid. It contains albumin and potassium albuminate (9.2 per cent.); like watery egg-albumin, it is viscid, flows with difficulty and coagulates at a temperature of 75 C. into a white mass. On standing in the cold a gelatinous coagulum of albumin sepa- rates, in which concentrated mineral acids, metallic salts, tannic acid, chlorin-water and bromin-water cause a precipitate; the precipitate produced by alcohol can be redissolved by water. The total solids in the pancreatic juice of human beings equal 13.6 per cent. Among the salts are sodium chlorid, 7.3; sodium bicarbonate, 0.4; sodium phos- phate, 0.45; sodium sulphate, i.i in 1000, together with some lime and traces of magnesia, potassium sulphate and ferric oxid. The more rapid and the more profuse the flow of the pancreatic 304 THE DIGESTIVE ACTIVITY OP THE PANCREATIC JUICE. juice, the more deficient is the secretion in organic constituents, the inorganic components remaining almost the same. Nevertheless, the total amount of solid constituents secreted is greater under such circum- stances than when the secretion is scanty. The freshly discharged juice ^contains traces of leucin and soaps. In pancreatic juice that is no longer fresh, chlorin induces a red color, as does crude nitric acid in the putrefying juice, by the production of indol. Rarely the juice forms concretions in the pancreas, principally of calcium carbonate. In cases of diabetes dextrose has been found in the pancreatic juice; in cases of jaun- dice, urea. THE DIGESTIVE ACTIVITY OF THE PANCREATIC JUICE. The presence of four hydrolytic ferments, or enzymes (an amyloly- tic, a proteolytic, a lipolytic, and a milk-curdling ferment), makes the pancreatic juice a most important digestive fluid. The amylolyiic activity is due to the ferment amylopsin, which ap- pears to be identical with the ptyalin of the saliva, though it acts more energetically, both upon raw and upon boiled starch and glycogen. At the temperature of the body almost immediately, but more slowly at a lower temperature, it converts the substances named into maltose, isomaltose and dextrin, as does the saliva. Even cellulose itself is said to be digested and gum to be transformed into sugar, but inulin remains unchanged. The amylopsin is precipitated by alcohol and it remains dissolved in glycerin without material enfeeblement. All agencies that disturb the diastatic activity of the saliva also abolish that of the amylopsin, although admixture of acid gastric juice, as its hydrochloric acid is in combination, or of bile, is without injurious effect. The ferment is isolated by the same method as that by which salivary ptyalin is obtained, but in this process the peptic ferment is at the same time precipitated with it. In addition to this diastase, the pancreatic juice contains a second diastatic ferment, by which maltose and isomaltose are transformed into dextrose. Saliva contains hardly a trace, and blood-serum more of this ferment than of diastase. The addition of bile, as well as of various neutral salts (in about 4 per cent. solution), increases the diastatic activity, and in the following order: potassium nitrate, sodium chlorid, ammonium chlorid, sodium nitrate, sodium sulphate, potassium chlorate, ammonium nitrate and ammonium sulphate. The proteolytic activity is due to the ferment trypsin, which at the temperature of the body transforms the albuminates, in the presence of an alkaline medium, without previous swelling, first into albu- moses (hemi-albumose and anti-albumose) , also designated propeptones, and finally into true peptones, also designated tryptones. Previous swelling of the proteids by means of hydrochloric acid, as well as an acid reaction in general, have a tendency to prevent this transformation. The albumoses of tryptic digestion have the character of the deutero- albumoses. Two kinds of peptones are formed, namely hemi-peptone, which later breaks up into the amido-acids, and antipeptone, which does not undergo further decomposition. Trypsin peptonizes all proteids, casein, vitellin, elastin, mucin, and nuclein, while neurokeratin, keratin and amyloid remain insoluble. Glutin and the gelatin-yielding substance, swollen by acids are changed into gelatin-peptone, and the latter is not further changed. Oxyhemo- globin decomposes into albumin and hemochromogen. Pancreatic ex- THE DIGESTIVE ACTIVITY OF THE PANCREATIC JUICE. 305 tract first affects milk-casein in such a manner that it is coagulated by heat, after which it is peptonized. In other respects, trypsin has an action like that of pepsin upon tissues containing albumin. Casein is almost wholly digested by trypsin. The tryptic ferment, which is also present in the pancreas of new-born infants, is carried down mechanically from the pancreatic juice diluted with water, by the production of a voluminous precipitate, with collodion. The precipitate is washed and dried, and then the collodion is dissolved out in a mixture of ether and alcohol. The residue is soluble in water, and represents the ferment. Kuhne further separates with especial care the albumin still combined with the ferment in the aqueous extract of the gland, and thus secures the ferment in a purer form. It is soluble in water, insoluble in alcohol and in pure glycerin. As trypsin is destroyed by hydrochloric acid, it is not advisable, as in the presence of weakened digestion, to administer trypsin by the mouth. In a dried state it can be heated to a temperature of 140 C. without injury; in a moist state, if pure, to 50 C.; and mixed with salts or with albumoses and peptones, to 60 C. Method: For testing trypsin, gelatin is especially useful, being liquefied in a test-tube at the temperature of the body: 7 grams of gelatin boiled with 93 grams of an aqueous solution of thymol. For antiseptic purposes thymol should be added also, after nitration, to the fluid to be tested for the presence of the ferment. Trypsin results through the taking up of oxygen within the pan- creas, from a mother- substance, zymogen, which collects in the interior of the secreting cells in smallest amount between the sixth and the tenth hour, and in largest amount, on the other hand, sixteen hours after eating. It can be extracted from fresh glands by glycerin or by water. In aqueous solution this body yields the ferment. Within the excised pancreas the same result occurs on treatment with strong alcohol. The addition of bile, sodium chlorid. sodium glycocholate and carbonate, as well as carbon dioxid, increases the activity of the ferment, while magnesium sul- phate and sodium sulphate enfeeble its action. With continued action of the trypsin upon the hemipeptone pro- duced, this is converted in part into the amido-acids: leucin (C 6 H 13 NO2), tyrosin (C 9 H U NO 3 ), aspartic or amidosuccinic acid (C 4 H 7 NO 4 ) in the diges- tion of fibrin and glutin, glutamic acid (C 5 H 9 NO 4 ), and butalanin or amidovalerianic acid (C5H n NO 2 ). Gelatin-peptone, according to Nencki, on further decomposition yields glycin and ammonia. The amido-acids produced may be partly absorbed as such and may be consumed in the circulation. The following bases also occur: xant bin-bases , lysin, lysatinin, argi- nin, together with ammonia and a body that becomes reddened by chlorin-water or bromin-water. If the action be continued still further, matters having a fecal odor result, and with especial rapidity when the reaction is alkaline, also indol (C 8 H 7 N), skatol (C 9 H 9 N), and phenol (C 6 H 6 O), volatile fatty acids with the development of hydrogen, carbon dioxid, hydrogen sulphid, marsh- gas and nitrogen. These products of decomposition, however, result wholly from putrefaction of the preparations. This can be prevented by the addition of salicylic acid or thymol, which destroys the putre- factive organisms that are always present. Prolonged boiling of the albuminates with dilute sulphuric acid, like the action of trypsin, produces first peptone, then leucin and tyrosin, and glycin from gelatin. Hypoxanthin and xanthin result in this way on boiling fibnn, the former als( from long-continued boiling of fibrin with wuti v r. Leucin, tyrosin, glutamic and aspartic acids, together with xanthm-bodies, 306 THE DIGESTIVE ACTIVITY OF THE PANCREATIC JUICE. result also in the germination of certain plants, by reason of which there is a resemblance between the transformation and the consumption of nutritive mate- rials in seeds and the digestive effects of ferments. The lipolytic activity depends on the presence of a ferment termed steapsin or pialyn, which exerts its action more especially on the neutral fats. This action is two-fold: (i) they are transformed into a fine, permanent emulsion, and (2), by taking up water, they undergo a cleav- age into glycerin and fatty acids. C57H 110 0. + 3 H 2 = C 3 H 8 3 + 3(CH,A) Tristearin + Water = Glycerin + Stearic Acid. The addition of bile increases this action in the rabbit very consid- erably. This cleavage action is due to a ferment, especially decomposed by acids, but which has not yet been isolated. Lecithin is split up by this ferment into glycerinphosphoric acid, neurin and fatty acids. After decomposition is complete, the fatty acids are in part united with the alkalies of the pancreatic juice and the intestinal fluid to form fatty-acid alkalies, or soaps; and in part emulsified in the alkaline in- testinal juice. Both the emulsion and the soap-solution are capable of being absorbed. After extirpation of the pancreas in the dog, the digestion and absorption of fats are correspondingly diminished. If the fat to be emulsified contains free fatty acids, as is the case with all of the fats of the food, and if the fluid at the same time has an alkaline reaction, emulsification takes place with extraordinary rapidity. A drop of cod-liver oil, which likewise always contains some free acid, placed in a 0.3 per cent, soda-solu- tion, is at once broken up into fine emulsion-granules. First a hard soapy mem- brane is formed on the surface of the oil-drop; this, however, is quickly dissolved and small drops are thereby torn away. The fresh surface becomes again covered with a layer of soap and the process is continually repeated. The soaps produced themselves in turn act as emulsifiers. If the amount of oleic acid contained in the oil and the concentration of the soda-solution are increased, so-called "myelin- forms" are produced, that is, forms like those that appear when fresh nerve-fibers are teased in aqueous liquids. Animal fats furnish an emulsion more readily than vegetable fats, castor-oil not furnishing any at all. The fatty acids also may undergo still further decomposition through the action of the fat-splitting ferment, with the production of carbon dioxid and hydrogen even, in the absence of microorganisms. Danilewsky isolated the four pancreatic ferments in the following manner: If an acid infusion of dog's pancreas is super-saturated with magnesium oxid, the precipitate carries the fat-ferment down with it. Collodion added to the filtrate precipitates the trypsin; the precipitate is collected; and the collodion is dissolved out by a mixture of ether and alcohol. The diastatic ferment is contained in the filtrate from the collodion-precipitate. For testing the digestive activity of the pancreas an extract of the swollen and reddened gland may be prepared after trituration with the aid of concentrated solution of sodium chlorid. Triturated pancreas, which has lain for a day, can also be extracted with glycerin or chloroform-water. Alcohol precipitates the fer- ments in these extraction-fluids. Kuhne renders the minced pancreas free from water and fat by means of alcohol and ether, and pulverizes it. The powder, to which 10 parts of o.i per cent, salicylic acid solution at blood-heat are added, exhibits the activity of the ferments. An extract of the pancreas, prepared rapidly and at a high temperature with a 0.7 per cent, solution of sodium chlorid, contains almost alone the sugar-forming ferment, which is absent from the gland in the state of hunger. After long-continued maceration at a later period trypsin prin- cipally is obtained. To demonstrate the effects of the pancreas Setschenow proceeds as follows: Minced calf's pancreas is infused with less than double its volume of water and is kept at a temperature of 38 C. for five hours. The decanted fluid is strained, shaken with ether, and alcohol is added until a precipitate forms. The latter is spread uniformly upon filter-paper by filtration, and the paper is dried at a tern- THE SECRETION OF THE PANCREATIC JUICE. 307 perature of 40 C A strip of this paper about the length of a finger immersed and fat 4 ^ ^ ^^ ^^ * L[d P * UQ f ^% U P n starfhes^umln The pancreas of new-born infants contains no diastatic ferment, but both peptic and fat-splitting ferments. Diseases of infants, diarrhea at times appear , h V h-t a Tt +1 6Ct V he aCtivity f the P ancre *s- Slight diastatic p P ower of the fir^ ear ^ m f Ufe> com P lete ac tivity only after the lapse The milk-curdling activity depends on the presence of a ferment according to W. Kuhne and W. Roberts, which can be extracted by means of a concentrated solution of sodium chlorid. The pancreas also prepares a sugar-splitting ferment. If a solution of sugar is digested with an aqueous or glycerin extract of pancreas, the amount of sugar diminishes. THE SECRETION OF THE PANCREATIC JUICE. In the case of the pancreas, a resting stage, in which the gland is flabby and pale yellow, and a stage of secretory activity, in which the organ appears swollen and pale red, can be distinguished. The latter occurs only after the ingestion of food, and results probably in consequence of reflex excitation through the nerves of the alimentary canal, and ap- parently in consequence of the moistening of the intestinal mucous mem- brane with the acid gastric contents, for acids are the most powerful excitants of this secretion. W. Kiihne and Lea found that all the lobules did not take part in the secretory activity at the same time. The pan- creas in herbivora secretes continuously. * According to Bernstein and Heidenhain, the secretion begins to flow with the entrance of the food into the stomach, the quantity reaching its maximum in the second or third hour. After this the amount de- creases between the fifth and the seventh hour; then, in consequence of the passage of all of the dissolved matters into the duodenum, it rises again between the ninth and the eleventh hour, and finally falls gradually between the seventeenth and the twenty-fourth hour, to the point of complete cessation. ^ During the act of secretion the blood-vessels behave like those of the salivary gland after stimulation of the facial nerve; they are dilated, the venous blood being bright red. It is, therefore, probable that a similar nervous mechanism is active here. In general, the activity of the gland is in large measure dependent upon an adequate blood-supply; anemic conditions impair the secretory processes. The secretion, in the rabbit, is under a secretory pressure of over 17 mm. of mercury. The nerves are derived from the hepatic, splenic and superior mesenteric plexuses, to which the pneumogastric and splanchnic nerves send branches. The secretion of the gland is excited by stimulation of the medulla oblongata, of the splanchnic nerves (feebly), of the peripheral stump of the pneumogastric nerve, in consequence of which the amount of ferment in the juice is increased, as well as of the gland itself by means of induction-currents. Reflex increase in the secretion is brought about by stimulation of the central stump of the lingual nerve, at times also by that of the central stump of the pneumogastric nerve. The secretion is suppressed by atropin, by excitation through the act of vomiting, as well as by stimulation of the pneumogastric nerve or its central stump, as well as of other sensory nerves, as, for example, the crural and sciatic nerves. Destruction of the accessible nerves of the pancreas surrounding the blood-vessels renders the stimulation mentioned ineffective. On the other hand the secretion of a watery, paralytic, slightly active secretion becomes permanent; and the amount is then no longer modified by the ingestion of food. 308 THE STRUCTURE OF THE LIVER. Fat and water, further pilocarpin and physostigmin, excite pancreatic secre- tion. Solutions of neutral and alkaline salts of the alkaline metals exert an in- hibitory action. Animals tolerate ligation of the pancreatic duct. It is a remark- able fact that the duct may regenerate spontaneously. This operation may, how- ever, be followed by cyst-formation in the ducts and atrophy of the glandular structure. After total extirpation of the pancreas, the digestion of albumin, fat and starches is impaired. The severe diabetes that develops immediately after extirpation of the pancreas and which has been observed also in human beings after degeneration of the pancreas, is of obscure origin. THE STRUCTURE OF THE LIVER. The liver is included among the compound tubular glands. Its development shows that with its excretory ducts it evolves in the form of a reticulated tubular gland. The globular, polygonal hepatic acini (lobules, islands), flattened one against the other, from i to 2 mm. in diameter, are considered as the ultimate macroscopic units of the gland. They show the following histological peculiarities: The liver cells (Fig. 116, II, a), 34 or 35 ^in diameter, are irregularly polyhedral, consisting of soft, friable protoplasm, filled with pigment-grantiles. They have no membrane, and contain one or more spherical nuclei, with nucleoli, and are so arranged that they radiate from the centre of the acinus in longer or shorter con- nected lines toward the surface of the lobule. Thus arranged they are in part surrounded by the more delicate bile-ducts (Fig. 116, I, x), in part separated one from the other in rows by the coarse network of blood-capillaries (d d) . In the state of hunger the liver-cells are finely granular and deeply clouded (Fig. 117, i). About thirteen hours after suitable nourishment the cells contain coarse, glistening flakes of glycogen (2). At the same time the protoplasm is condensed on the surface, whence a network extends toward the center of the cells, in which the nucleus is suspended. The liver-cells often contain fatty granules. The Blood-vessels of the Lobule. (a) Ramifications of the venous system. If the branches of the portal vein, well supplied with muscular fibers, and entering through the transverse fissure, be followed, small vessels will finally be found, after free dendritic branching, that, approaching from various directions, converge at the limits of the acini, and here enter into communication through capillary anasto- moses, forming the interlobular veins (Fig. 116, V, i). From these veins capillary vessels (c c) pass from the entire periphery of the acinus toward its center. They are relatively large (from 10 to 14 // in diameter) and form a longitudinal network in a radiating direction; and between them rows of connected hepatic cells, liver-cell columns (d) , are always lodged. The capillaries are so arranged that they run along the edges of the rows of cells, and never between the surfaces of two adjacent rows. The radiating course of the capillaries necessarily brings it about that these vessels must unite at the center of the acinus to form the beginning of a larger vessel. This is the central or intralobular vein (V. c) which, m turn, piercing the lobule vertically, makes its exit at one point and, reaching the surface unites, as the sublobular vein (V. a), with similar vessels from neighboring acini, to form larger trunks that (100 // in diameter) represent the roots of the hepatic veins. The trunks of this great system of venous radicles leave the gland at the blunt edge of the liver. (6) Ramifications of the Hepatic Artery. The branches of the hepatic artery, throughout their entire course, accompany the larger branches of the portal vein, to which, as well as to the adjacent larger bile-ducts, they supply nutrient capillaries. These branches enter into numerous anastomotic communications among them- selves. The small capillaries pass mainly from the periphery of the acinus into the capillaries of the portal system (Fig. 116, i i). Those arterial capillaries, how- ever, that lie in the thicker connective tissue upon the larger venous and biliary branches (rr) pass over chiefly into two venous trunks that, accompanying the corresponding arterial branches for some distance, empty into branches of the portal vein. Individual arterial branches pass up to the surface of the liver, where they form a wide-meshed nutritive network, particularly under the peritoneal covering. The small venous radicles collecting from this point also reach the ramifications of the portal vein. The Biliary Passages. The finest biliary passages, bile-capillaries, originate from the center of the acinus, and likewise within its entire interior, as membrane- less, regularly anastomosing straight ducts, i or 2 ^ in diameter. They form a THE STRUCTURE OF THE LIVER. 309 polygonal mesh about each liver-cell (Fig. 117, 3 ). The ducts almost always lie midway between the surfaces of two adjacent liver-cells (Fig. 116, II, a) as true intercellular passages or secretory spaces. When the cells fall apart in the process of maceration, they retain only semicircular depressions. The finest ducts of the bile-capillaries have been observed to penetrate the interior of the liver-cells and to communicate here with roun -s to communicate here with round, secretory vacuoles containing bile (Fig 117 7) along the edges of the rows of liver-cells, while the As the blood-capillaries run e rows o ver-ces, we te biliary ducts run along the surfaces of the cells, both systems of ducts are always at a definite distance from one another (Fig. 118). " In human beings individual bile-ducts sometimes run also along the edges of the cells, so that they must then act as intercellular ducts of 3 or 4 cells This arrangement is said to predominate in the embryonal liver. In addition to in- jection, the capillaries can be made visible by staining by Golgi's method V.i V. FIG. 116. I. Diagrammatic Representation of an Hepatic Lobule: V. i., V. i, interlobular veins; V. c, central vein; c, capillary between the two; V. s, sublobular vein; V. v, vascular vein; A A, branches of the hepatic artery, approaching the capsule of Glisson and the larger blood-vessels at r r, and forming the vascular vein further on, entering the capillaries of the interlobular veins at i i; g, branches of the bile-duct, dividing at x x between the liver-cells; d d, situation of liver-cells in the capillary network. II. Isolated liver-cells, at c lying upon a capillary blood-vessel and forming a fine bile-duct at a. Within the peripheral, cortical portion of the lobule the ducts, without walls, increase in size by anastomosis of neighboring ducts. They then leave the acinus, in order, from this point, uniting between the lobules (Fig. 116, g) with adja- cent ducts, to form larger bile-ducts, with numerous anastomoses. These, in com- pany with the branches of the hepatic artery and the portal vein, finally leave the transverse fissure of the liver as a collecting duct, the hepatic duct. The finer interlobular bile-ducts possess a structureless membrana propria with low epithe- lium. The larger (Fig. 119) exhibit a double membrane constituted of connective tissue and elastic fibers, the internal layer being c-sjuvially supplied with blood- capillaries and bearing a single layer of cylindrical epithelium. Only in tin- largest branches, and in the gall-bladder, does this internal layer Kv<>me an independent mucous membrane, with submucosa. Unstriped muscle-fibers are found in isolated 3 io THE STRUCTURE OF THE LIVER. FIG. 117. A, Liver-cell, in the state of hunger; 2, filled with masses of glycogen; 3, sur- rounded by bile-capillaries. bundles in the main ducts (longitudinal and circular especially in the lower portions of the bile-ducts), as well as in a delicate longitudinal and circular layer in the gall-bladder. The movements here are slowly rhythmic and peristaltic. The mucous membrane of the gall-bladder is provided with folds and comb-like de- pressions. The epithelium is a single layer of cylindrical epithelium with a basal membrane and intervening mucous goblet-cells. Small mucous glands are found in the mucous membrane of the large bile-ducts and of the gall-bladder. The connective tissue of the liver enters the portal fissure as a sheath (capsule of Glisson) for the vessels, and, mixed with elastic tissue, finally reaches the periphery of the acini, where in the pig, the camel and the polar bear it forms a clearly demonstrable capsule, but in human beings is in- conspicuous. Delicate elements can, however, be followed even into the acinus, nucleated star-cells and a network of delicate reticular fibers, which effect the fixation of the elements. The connective tissue of the acini not rarely undergoes considerable increase in drunkards, and its hyperplasia may even cause destruction of the contents of the acinus by pressure (cirrhosis of the liver). In this thickened, interacinous connective tissue newly formed bile-ducts have been found, and likewise in the cicatricial connective "tissue of the "corset-liver." The lymph-vessels begin as pericapillary ducts in the interior of the acinus. Further on they run within the walls of the hepatic veins and the branches of the portal^vein; then they surround the venous branches. The larger vessels, formed from the union of the inter- lobular passages, leave the organ in part at the trans- verse fissure, in part with the hepatic veins, and in part at different points on the surface. At the blunt edge of the liver they form a close meshwork and pass through the triangular, he- pato-renal and suspensory ligaments. The nerves of the hepatic plexus, constituted in part FIG. 118. Blood-capillaries, Finest Biliary Ducts, and Liver- cells, in Their Mutual Relations in the Rabbit's Liver (after E. Hering): B, blood-vessel; D, finest biliary duct, in cross-section; F, finest biliary duct; K, nucleus of liver-cell. C. FIG. 119. Interlobular Bile-duct from the Human Liver (after Schenk) : R, circular fibrous layer; C, cylindrical epithelium. of Remak's fibers, in part of medullated fibers fiom the sympathetic and pneu- mogastric nerves, follow the ramifications of the hepatic artery. Ganglia are placed in their course in the interior of the organ. The nerves are in part vasomotor in nature. According to Pfliiger, other nerve-fibers enter into direct connection with the liver-cells, as is the case in the salivary glands. The muscle-cells of the bile-ducts contain motor filaments. CHEMICAL CONSTITUENTS OF THE LIVER-CELLS. 311 The celiac plexus sends trophic and vasomotor nerves to the liver. Destruc- tion of this plexus therefore causes degeneration of the liver-cells, and dilatation of the hepatic artery. The pneumogastric nerve supplies dilator-fibers to the vessels, and the greater splanchnic motor branches to the muscles of the bile- ducts. CHEMICAL CONSTITUENTS OF THE LIVER-CELLS. Proteids. The fresh, soft liver-parenchyma has an alkaline re- action. After death, coagulation takes place, with cloudiness of the cell-contents ; the tissue becomes friable and gradually acquires an acid reaction. This process is suggestive of rigor mortis, and is due to a myosin-like, post-mortem coagulating albuminous substance. The liver contains, further, a proteid body coagulable at 45 C., another coagulable at 70 C., and one slightly soluble in dilute acids and alkalies. The nuclei contain nuclein. The connective tissue yields gelatin. Glycogen, 6C 6 H 10 5 + H 2 O, or animal starch, from 1.2 to 2.6 per cent., is a carbohydrate closely allied to inulin, soluble in water, and diffusible with difficulty, which surrounds the nuclei of the liver-cells in amorphous granules (Fig. 117, 2), though not always present and not always found in equal amounts in all parts of the liver. The glycogen in the liver represents the excess of carbohydrate material, which, after the ingestion of suitable foods, is temporarily stored like the starch in the plants. It is subsequently transformed into sugar and consumed by the tissues. t Qualitative Determination. Glycogen is stained deeply red by iodin (best dis- solved by means of potassium iodid in a concentrated solution of sodium chlorid) , like inulin, even in microscopic sections hardened in alcohol. Organs containing ?lycogen, boiled with an excess of sodium sulphate, yield an opalescent filtrate, f the organs, as, for example, the liver, still contain diastatic ferment, the glycogen, after being kept warm for several hours, will be converted into sugar, and, as already stated, the resulting filtrate remains clear. Quantitative Estimation. According to Kulz's modification of Brucke's method, the coarsely minced liver is thrown into boiling water immediately after death and boiled for half an hour. It is then crushed and potassium hydrate (4 grams to 100 grams of liver) is added. Evaporation over a water-bath to double the weight of the piece of liver employed is permitted to take place until in the course of three hours all is dissolved. After cooling, the mixture is neutral- ized with hydrochloric acid, and the albumin, together with the lime, is precipitated by means of hydrochloric acid, and potassio-mercuric iodid. Filtration is now practised, the precipitate being taken from the filter four times, mixed with a few drops of hydrochloric acid and potassio-mercuric iodid in water to the consistency of broth and filtered. All of the glycogen is now contained in the filtrate, to which, with stirring, double the volume of 96 per cent, alcohol is added. The glycogen deposited in the course of twelve hours is placed upon the filter, washed with 62 per cent, alcohol, then with absolute alcohol, with ether, again with absolute alcohol and dried at 110 C. Should the fluid remain cloudy after addition of hydrochloric acid and potassio-mercuric iodid, two parts of 98 per cent, alcohol are added and the filtered precipitate is dissolved in 2 percent, potassium hydrate, then neutralized with hydrochloric acid and now all of the albumin can be precipitated by repeated addition of hydrochloric acid and potassio-mer- curic iodid again. According to Seegen, dextrin is present in the liver in addition to glycogen. Rabbit's liver contains about three times as much glycogen in winter as in summer. The following are to be considered as the sources of glycogen in the liver: (i) The carbohydrates of the food, after they have been con- verted into dextrose in the alimentary canal; only the sugars ferment- able by yeast form glycogen, and not those incapable of fermentation; 312 CHEMICAL CONSTITUENTS OF THE LIVER-CELLS. and (2) the proteids, including gelatin. If the proteids are a source of glycogen, it must result from a non-nitrogenous derivative of them. Pfluger considers the formation of glycogen from albumin a synthetic process. The molecular group CH 2 , found in albumin, as well as in the fatty acids, must be transformed by oxidation into CHOH. The cells taking part in the formative process may, however, also utilize this group CHOH wherever it is found already prepared, as in sugar or in glycerin. Also fats (olive-oil), glycerin, taurin and glycin (the latter through decomposi- tion into glycogen and urea) , have been designated as the source of glycogen. In rabbits, the production of glycogen is increased by the administration of asparagin, ammonium carbonate or urea. The excessive production of acid in cases of diabetes, demonstrated by Stadelmann, fixes the ammonia and thus materially diminishes the production of glycogen. Ligation of the common bile-duct results in diminution of the glycogen in the liver. The liver after this operation appears to have lost the property of form- ing glycogen from suitable material brought to it. Also ligation of the hepatic artery renders the liver free from glycogen. After excluding the portal circulation the amount of sugar contained in the blood decreases. With reference to the occur- rence of glycogen elsewhere reference may be made to p. 466. If large amounts of starch, grape-sugar, cane-sugar, levulose and maltose are added to the proteids of the food, the amount of glycogen in the liver is greatly increased, while on a pure albuminous or fatty diet it is considerably decreased ; the state of hunger may cause it to dis- appear entirely. Injection of grape-sugar or of glycerin into a mesen- teric vein of a fasting rabbit causes the appearance of glycogen in a liver previously free from it. The living liver-cell is capable of producing glycogen in considerable quantities only from the two kinds of sugar capable of direct fermentation, namely dextrose and levulose. The non-fermentable sugars are not converted into glycogen, and cane-sugar and maltose only in so far as they are transformed in the intestine into dextrose. As the infant consumes milk-sugar, it must form glycogen from albu- min. Forced muscular movement rapidly renders the liver of the dog free from glycogen. Reduction of temperature .diminishes the amount of glycogen in the liver. The rigid liver after death contains dextrin and grape-sugar. Glycogen is also present in the liver for a considerable time after death, as well as in the muscles. Under normal conditions, the glycogen in the liver is gradually transformed in small amounts into grape-sugar. The amount of sugar normally present in the blood is from 0.5 to i in 1000. The blood in the hepatic veins may contain somewhat more. Increased transforma- tion into sugar occurs only in connection with marked circulatory dis- turbances in the liver, as a result of which the blood of the hepatic veins comes to contain a larger amount of sugar. The glycogen undergoes this transformation, likewise, soon after death, when the liver is always found to contain a larger amount of sugar and a smaller amount of gly- cogen. The active ferment necessary for this process can be obtained from an extract of the liver-cells, by the method employed to obtain ptyalin. Nevertheless, it is said not to be formed in the liver-cells, but only reaches the liver to be quickly stored up, through the blood, within which the ferment is always formed with rapidity so soon as the move- ment of the blood undergoes marked disturbance. This transforming ferment develops also as a result of the solution of red blood-corpuscles ; and as a constant slight destruction of red blood-corpuscles must surely be assumed to take place within the liver, a source is thus provided DIABETES MELLITUS. 313 for the production of the ferment through the action of which small quantities of sugar are continually formed in the liver. As the liver is thus the seat for the production of sugar, extirpation of this organ or ligation of its vessels is followed by disappearance of the sugar con- tained in the blood. The grape-sugar formed in the liver is destroyed in part in the blood- stream, on its way through the tissues, in part by a special ferment, which appears to be derived principally from the pancreas, and to be carried by the blood-corpuscles. A portion of the sugar in the blood is converted in the muscles into glycogen. According to Kiilz and Vogel, the same process takes place in the liver in the formation of sugar from glycogen as results from the action of the saliva and the pancreatic juice, with the production likewise of maltose and isomaltose. According to E. Cavazzani, irritation of the celiac plexus causes the production of sugar in the liver, in connection with which the liver-cells undergo morphologic change. Further, /a/5 are observed in the liver-cells, in the form of granules, as well as free in the bile-ducts ; occasionally when the diet is rich in fat (in greater amount in drunkards and tuberculous patients), olein, pal- mitin, stearin and volatile fatty acids are found. Further, sarcolactic acid, traces of cholesterin, jecorin, finally small amounts of urea (in increasing amount in the warm, "surviving" liver), uric acid; and leucin, ty rosin (guanin?), sarcin, xanthin, and cystin pathologically in conjunction with putrefactive disorders, may be present. The liver-cells contain pigments, which are partly soluble in feebly alkaline water, partly in chloroform. The pigment soluble in water, designated ferrin, varies from yellow to red in color and contains almost all o the iron of the liver. The latter can be demonstrated directly by means of potassium ferrocyanid or ammonium sulphid. The pigment soluble in chloroform, designated chofechrome, can be extracted from pulverized dried liver. It stands midway between bile-pigment and the lipochromes. The inorganic constituents of the liver are potassium, sodium, calcium, magnesium and manganese. Iron in organic combination with albumin (in ferratin) is present in the liver to the amount of about 6 per cent. Abstraction of blood together with albumin-hunger causes its disappear- ance. It is utilized in the production of new blood. Chlorin, phosphoric, sulphuric, carbonic and silicic acids may also be present ; and copper, zinc, lead, mercury and arsenic have been found deposited in the liver acci- dentally. DIABETES MELLITUS. The formation of large amounts of grape-sugar by the liver and their entrance into the blood and into the urine (glycosuria, diabetes melhtus) have been brought into relation with the normal conditions already mentioned. Extirpation of the liver in. the frog or destruction of the liver-cells (fatty degeneration from phos phorous or arsenical poisoning) does not cause the appearance of this phenomenon. It occurs a few hours after injury to a particular spot (center for the vasomotor nerves of the liver) on the floor of the lower portion of the fourth ventricle Bernard's sugar-puncture, piqure) ; further, after division of the vasomot paths in the^ spinal cord from above downward to the exi for the liver that is to the lumbar portion, in the frog to the fourth vertebra. Division or paralvsis of the vasomotor conducting paths from the ceni the liver results in glvcosuria. According to recent researches 1 >y I- ranjois I- ranck and Hallion, the vasomotor nerves of the liver (for the hepatic artery anc portal vein) arise between the sixth dorsal and the second lumbar nerves am 314 DIABETES MELLITUS. pass through the communicating branches into the splanchnic nerves. According to the opinions of earlier investigators, all of the paths, however, do not pass through the spinal cord alone. A number of vasomotor fibers for the liver leave the spinal cord at a higher level, and pass further on in the course of the sym- pathetic nerve to the liver. Thus, destruction of the uppermost, as well as of the lowest, cervical ganglion, and of the first dorsal ganglion, of the abdominal ganglia, often also of the splanchnic nerves, is followed by glycosuria. The paralyzed, dilated vessels render the liver exceedingly vascular, and the blood-stream in them is slowed. This disturbance of the circulation gives rise to the presence of a large amount of sugar in the liver, as the blood-ferment has time to effect transformation of the glycogen. Irritation of the sympathetic nerve at the last cervical and first dorsal ganglia causes contraction of the hepatic vessels at the periphery of the acini, with anemia. It is a remarkable fact that glycosuria when present can be removed by division of the splanchnic nerves. This is explained by the cir- cumstance that the enormous hyperemia of the intestines occurring after this operation renders the liver anemic. Also a number of poisons that paralyze the vasomotor nerves of the liver cause diabetes in the same manner, namely curare, when artificial respiration is not maintained; carbon monoxid, amyl nitrite, orthonitrophenyl-propionic acid and methyldelphinin ; less constantly morphin, chloral hydrate "and others. The toxic products of some of the infectious diseases also act in the same way at times. Blood-stasis of other sort in the liver also appears capable of caus- ing glycosuria, as, for example, after mechanical stimulation of the liver. In this category probably belongs the glycosuria following the injection of dilute saline solutions into he blood, as a result of which the changes in the shape of the red corpuscles cause stasis. Also the fact that repeated venesection makes the blood richer in sugar may, perhaps, be explained by the slowing of the circulation. Persistent irritation of peripheral nerves may also be active through a reflex influence upon the center for the vasomotor nerves of the liver. The appearance of sugar in the urine has sometimes been observed as a result of irritation of the central stump of the pneumogastric nerve, likewise after irritation of the central stump of the depressor nerve. Even division and central irritation of the sciatic nerve may cattse the appearance of sugar from the urine ; in this way is explained the occurrence of glycosuria in cases of sciatica and other nervous disorders. According to Schiff, stagnation of the blood in various extensive portions of the body is said to increase the development of the ferment in the blood to such a degree that diabetes results. Qf this character must be considered the glycosuria that occurs after compression of the aorta or the portal vein, although the pressure exerted under such circumstances may, perhaps, paralyze nerve- paths concerned. According to Eckhard, injury to the vermis of the cerebellum, in the rabbit, is said to bring about diabetes. In human beings, also, affections of the nervous structures mentioned may cause diabetes. Various explanations have been assigned in elucidation of the ultimate cause of these symptoms: (a) The glycogen of the liver may without interference be converted into sugar, as ferment may be conveyed to the liver-cells from the blood-mass, in consequence of its stagnation. Therefore the normally functionating vasomotor system of the liver, and especially its center, is, in a certain sense, to be designated an inhibitory system controlling the production of sugar. (6) If it be assumed that, under normal conditions, a certain, even though small, amount of sugar flows continually from the liver into the blood, through the hepatic veins, diabetes might be explained as depending on the abolition of those metabolic processes (deranged combustion of sugar) that constantly remove this sugar from the blood under normal conditions. The following experiments appear to confirm this latter view: Independently of one another, v. Mering and Minkowski, as well as de Dominicis, observed that dogs become diabetic after total removal of the pancreas. According to Min- kowski, it is the function of the pancreas to consume the sugar of the blood. Lepine and Barral state that a ferment is produced in the pancreas that destroys the sugar in the blood; so that after extirpation of the pancreas, sugar must accord- ingly accumulate in the blood. The ferment is contained in abundance within the leukocytes in the portal vein; some is derived from the lymph, perhaps also from other abdominal glands. After extirpation of the pancreas, the blood con- tains little sugar-destroying ferment. Kolisch and von Stejskal found much jecorin. THE CONSTITUENTS OF THE BILE. 315 Pfluger expresses himself as follows as to the development of diabetes mellitus: The sugar formed by the liver in excessive amount, in consequence of abnormalyl increased nervous excitation, stimulates the pancreas for it is possible that this gland takes part in the synthetic production of fat from sugar or the fat-forming organs to the production of an increased amount of fat, so that often fat-formation takes place at the beginning of the disease. As soon as the fat-producing organs, exhausted and paralyzed from over-activity, are no longer capable of disposing of the sugar wholly or in part (which may also be the result of excessive ingestion of sugar) , this is excreted by the kidneys, because even the healthy body cannot assimilate the greater portion of the sugar as such, but only after it has been transformed into fats or into soaps. The living body strives to make good the resulting great loss in nutritive material by the assimilation of larger amounts of albumin and fat. Naturally a variety of diabetes is conceivable without hepatic disease as the result of paralysis of the pancreas, or of the fat -producing organs. Lepine's discovery of a glycolytic ferment yielded to the blood by the pancreas, which decomposes the sugar in the blood in some as yet unknown manner, and which is absent or diminished in cases of diabetes, would readily accord with the foregoing hypothesis. In the presence of pancreatic diabetes, puncture of the floor of the fourth ventricle increases the excretion of sugar; likewise, remarkably, the addition of raw pancreas to the food. (c) Phloridzin, a glucosid from the bark of the roots of cherry-trees and apple- trees, after ingestion causes the sugar normally present in the blood to pass rapidly over into the urine, so that the latter contains a larger and the former a smaller amount of sugar. (d) According to Biedl, diabetes occurs after ligation of the thoracic duct in the dog. The enormous need of food and drink, together with the signs of consumption of the bodily tissues, is characteristic of diabetic patients. Not rarely, in severe cases, collapse-like coma is observed, which has been designated also diabetic coma, and during the existence of which the breath often smells of acetone, which can also be demonstrated in the urine. Diabetic patients living on an exclusive meat- diet exhibit diacetic acid in the urine, in addition to acetone. Neither acetone nor its antecedent, diacetic acid (which can be recognized by the reddening of the urine when dilute ferric chlorid is added drop by drop) , after the administration of which the urine contains much acetone, is, as direct feeding-experiments show, the cause of this coma; which is perhaps the result of excessive acid-production in the body, therefore an acid intoxication. To neutralize the acid, increased elimination of ammonia takes place from the body. The urinary tubules often ex- hibit signs of coagulation-necrosis, which can be recognized by a bright and swollen appearance of the necrotic cells of the tubules, v. Frerichs found, further, glyco- genic degeneration in Henle's loops, in the liver, the heart, the leukocytes and the lungs. The urine of diabetic patients is discussed on p. 501. THE CONSTITUENTS OF THE BILE. The bile is a transparent fluid varying from yellowish brown to dark green in color, of a sweetish, bitter taste, feeble musk-like odor, and feebly acid or neutral reaction. The specific gravity of human bile from the gall-bladder is between 1026 and 1032, while that collected from a fistula varies from 1010 to ion. The constituents of the bile are as follows : Mucus and in addition a considerable amount of mucoid nucleo- albumin, which together make the bile ropy, are products of the mucous glands and the goblet-cells of the mucous membrane of the bile-ducts. They are precipitated by alcohol, or dilute hydrochloric acid or dilute acetic acid. They cause rapid putrefaction of the bile. The two biliary acids : glycocholic acid and taurochplic acid, the called conjugate acids, combined with sodium (and with potassium in traces) to form sodium glycocholate and taurocholate, have a bitter taste and are dextrorotatory. In human bile, as in that of cattle, 316 THE CONSTITUENTS OF THE BILE. glycocholic acid predominates; in carnivora, the sheep, the goat, tauro- cholic acid. (a) Glycocholic acid, C 26 H 43 NO 6 , is decomposed by boiling with potas- sium or barium hydrate or with dilute mineral acids, and by taking up water splits into C 2 H 5 N0 2 + C 24 H 40 5 = C 26 H 43 N0 6 + H 2 O Glycin (glycocoll, + Cholalic or = Glycocholic Acid -f- Water, gelatin-sugar, amido- cholic Acid acetic acid) (b) Taurocholic acid, C 26 H 45 NSO 7 , decomposes with similar treatment and addition of water into C 2 H 7 NS0 3 + C 24 H 40 5 C 26 H 45 NSO ? + H 2 O Taurin (amido-ethyl- + Cholic Acid = Taurocholic Acid + Water. sulphuric acid, pris- matic crystals) Demonstration of the Biliary Acids. The bile is evaporated to one-fourth its vol- ume, triturated to a pasty mass with animal charcoal to remove the coloring- matter, and dried at 100 C. The black mass is extracted with absolute alcohol, which passes colorless through the filter. After a portion of the alcohol has been driven off by evaporation, the addition of an excess of ether causes at first a resinoid precipitate of salts of the biliary acids, which later pass over into a crys- talline mass of brilliant needles (Platner's crystallized bile) . The alkaline salts of the biliary acids obtained in this way are readily soluble in water or alcohol, but are insoluble in ether. From the solution of both salts neutral lead acetate pre- cipitates a portion of the glycocholic acid as lead glycocholate. The latter is collected on a filter, dissolved in hot alcohol, and lead sulphid is precipitated by hydrogen sulphid. After removal of the precipitate, the addition of water causes separation of the isolated glycocholic acid. If, after precipitation of the lead glycocholate, basic lead acetate is added to the filtrate, a" precipitate of lead taurocholate forms, uncontaminated, however, by lead glycocholate, from which the free acid is subsequently obtained by analogous treatment. According to Schotten and others, human bile contains, in addition to cholic acid, still another acid, fellic acid (C 2 ,H M O 4 ) ; the bile of cattle contains cholic acid(C 24 H 40 5 ). Of the products of decomposition of the biliary acids, glycin does not occur as such in the body, but only in the bile in combination with cholic acid, in the urine in combination with benzoic acid as hippuric acid, and finally in gelatin in. complete combination. Cholic acid is dextrorotatory, insoluble in water, soluble in alcohol; it is soluble with difficulty in ether, separating out in prisms. Its crystalline alkaline salts are readily soluble in water, like soap. With iodin, in direct light, it yields a yellow, in transmitted light a blue, crystalline combination. It occurs free only in the intestine. Cholic acid is replaced in the bile of some animals by a related acid, as, for example, in the bile of swine, by hyocholic acid; in the bile of geese, chenocholic acid is present. By boiling with concentrated hydrochloric acid or heating, dry, to 200 C., cholic acid is changed into an anhydrid dyslysin. Dyslysin is only an artificial product and never occurs in the intestines. When fused with potassium hydrate, it is changed back to potassium cholate. Pettenkofer's Test. The biliary acids, the cholic acids and their anhydrids, when dissolved or broken up in water, and on addition of two-thirds concentrated sulphuric acid (drop by drop, without permitting the temperature of the fluid to rise above 70 C.), and a few drops of a 10 per cent, solution of cane-sugar, yield a purplish-red transparent color, which shows two absorption-bands in the spec- trum, at E and F. Before examining a solution for the presence of biliary acids, the albumin must always be first removed, as the latter yields a similar reaction, although the red solution here is characterized by only one absorption-band. If only small amounts of biliary acids are present, the fluid must first be concentrated by evaporation. Cholesterin, stearic and oleic acids, as well as phenol and pyrocatechin, exhibit a similar reaction. Pettenkofer's test, therefore, is absolutely reliable only when THE CONSTITUENTS OF THE BILE. 317 the salts of the biliary acids in alcoholic extract are precipitated and thus isolated. It depends on the production, from the reaction between sugar and sulphuric acid, of furfurol, which is stained red in the presence of the biliary acids. Instead of sugar a o.i per cent, aqueous solution of furfurol may be employed with advan- tage for this reaction. The biliary acids are formed in the liver, as extirpation of this organ is not followed by their accumulation in the blood. The manner in detail in which the production of the nitrogenous biliary acids takes place, is unknown, although they are supposed to result from albumin. A generous proteid diet increases the secretion of bile. Taurin contains the sulphur of the proteid; the biliary acids contain from 4 to 6 per cent, of sulphur. Probably the substance of the red blood-corpuscles broken up in the liver takes part in their production. The Biliary Pigments. Fresh human bile and that of some animals is yellowish brown in color, due to the bilirubin present which is combined with an alkali. Under the influence of oxygen, heat and light, bilirubin is transformed by oxidation into a green pigment, biliver- din. This predominates in the bile of herbivora and of cold-blooded animals, and likewise often in the state of hunger. (a) Bilirubin, C 32 H 36 N 4 O 6 , from 0.15 to 0.25 percent, in human bile, according to Stadeler and Maly in combination with an alkali, crys- tallizes in transparent, sorrel, clinorhombic prisms. It is insoluble in water, but soluble in chloroform, by means of which it can be separated from biliverdin, which is insoluble in chloroform. It combines with alkalies as a monobasic acid and is thus soluble. It is identical with hematoidin. It is most easily prepared from red gall-stones formed of bilirubin and lime, which are triturated, the lime being dissolved out by means of hydrochloric acid. On agitation with chloroform the bilirubin is taken up. The derivation of bilirubin from hemoglobin is not to be doubted, on account of its identity with hematoidin. Probably red blood-corptiscles are broken up in the liver, and their hemoglobin is converted into bilirubin. In normal bile from a dog, a pigment is not rarely present having the spectral properties of methemoglobin, and which perhaps represents a body intermediate be- tween the hemoglobin and the coloring-matter of the bile. ' (b) Biliverdin, C 3 2H 36 N 4 O 8 , is an oxidation-stage of bilirubin, from which it can be obtained by various oxidizing processes. It is readily soluble in alcohol, with great difficulty in ether, and not at all in chlo- roform. It is present in large amount in the placenta of the dog. It has not as yet been possible to reconvert it into bilirubin by means of reducing agents. Gmelin's Test. Bilirubin and biliverdin, which, in addition to the bile, are occasionally found also in other fluids, at times in the urine, are demonstrated by Gmelin's test. If to the fluid containing the substances named are added several cubic centimeters of nitric acid and one drop of nitrous acid, which are permitted to flow carefully from the edge down the sides of a conical glass, without agitation, a play of colors results as follows: green (biliverdin), blue, violet, red and yellow. (c) If the addition of acid is stopped when the- color becomes 1>lue. thus pre- venting further oxidation, a stable transformation-product remains, name' cyanin. This has a blue color in acid solution, a violet color in alkaline solution, and it exhibits two ill-defined absorption-bands at D. Haycraft and Schofield were able to change this back by reduction with ammonium sulphid. Fluids containing biliary pigment, if boiled for from three to five minutes with one-third formalin, acquire an emerald-green color, which is changed to amethyst violet on addition of hydrochloric acid. (d) Small amounts of bilijuscin (bilirubin + water) have also been found in gall-stones and putrid bile. 318 THE CONSTITUENTS OF THE BILE. (e) Biliprasin (bilirubin + water + oxygen) has also been found under like conditions. (/) The yellow pigment finally obtained by the continued oxidizing effect of the nitric-acid mixture upon all of the biliary pigments is the choletelin of Maly, C 16 H 18 N 2 O 6 ; it is amorphous, and soluble in water, alcohol, acids and alkalies. (g) With addition of hydrogen and water in the intestine through the agency of bacteria bilirubin passes over into the hydrobilirubin of Maly, C 3 2H 40 N 4 07. The same result can be brought about artificially by treating an alkaline aqueous solution of bilirubin with actively reducing sodium-amalgam. Hydrobilirubin is but slightly soluble in water, more readily in salt-solutions or alkalies, alcohol, ether and chloroform, and it exhibits an absorption-band at F. This body, which, according to Hammarsten, occurs even in normal bile, is a constant pigment of the feces, from which, after acidulation with sulphuric acid, it can be extracted by absolute alcohol. Probably it is identical with the pigment of the urine, the urobilin of JafTe. Hydrobilirubin is formed in the intestine from ingested bile, being in part absorbed and excreted from the portal circulation through the bile. Hydrobilirubin to which a drop of sulphuric acid and some potassium nitrate are added again yields Gmelin's reaction. Fresh fecal matter, broken up in a porcelain dish in a concentrated solution of mercuric chlorid, yields a red color as the reaction of hydrobilirubin, while admixture of bilirubin causes a green color. Cholesterin forms transparent rhomboid plates (Fig. 92, d), is in- soluble in water, but soluble in hot alcohol, in ether or chloroform. In the bile it is kept in solution by the salts of the biliary acids. Choles- terin is not a secretory product of the liver, but a product of the disinte- gration of the epithelial cells of the biliary passages. It is most easily obtained from the so-called white gall-stones, which not rarely consist principally of almost pure cholesterin, by boiling the triturated cal- culi with alcohol. The crystals that separate on evaporation of the alcohol become red in color from the edges on addition of sulphuric acid (five volumes to one volume of water), and blue, like cellulose, on addition of sulphuric acid and iodin. Dissolved in chloroform, one drop of concentrated sulphuric acid produces a deep-red color. Moistened with a deep wine-yellow, alcoholic solution of iodin, the crystals exhibit green, blue and red coloration after addition of sulphuric apid. Dissolved in glacial acetic acid, addition of sulphuric acid produces first a rose- red, then a blue color. Other Organic Substances. Lecithin, or its decomposition-products, neurin and glycerin-phosphoric acid; palmitin, stearin, olein, as well as their sodium-soaps; . diastatic ferment; traces of urea, at times ethereal sulphuric acids ; acetic and propionic acids and traces of myris- tinic acid in the bile of cattle. Fat reaches the bile from the liver and, conversely, fat is in turn absorbed from the bile in the biliary passages (epithelial cells of the gall-bladder). Fresh unboiled bile decomposes hydrogen dioxid. Bacteria introduced into the blood- stream are in part eliminated by the bile. The inorganic constituents of the bile (from 0.6 to i per cent.) include sodium chlorid, potassium chlorid, 0.2 per cent, soda, alkaline sodium phosphate, calcium and magnesium phosphate, and an abundance of iron. The last yields the usual reactions of iron even in fresh bile, so that iron must be present in the bile in one of its oxygen-combinations. Finally, some manganese and silica are present. Freshly secreted bile from the dog contains more than 50, from the rabbit 109, volumes per cent, of carbon dioxid, in part combined with alkalies, in part absorbed, the latter being almost completely absorbed within the bladder. SECRETION OF BILE. 319 Analysis of Human Bile. Water, from 82 to 90 per cent., salts of the biliary acids, from 6 to n per cent., fats and soaps, 2 per cent.; cholesterin, 0.4 per cent.; lecithin, 0.5 per cent.; mucin, from i to 3 per cent.; ash, 0.6 per cent. The amount of sulphur contained in dry bile from a dog is from 2.8 to 3.1 per cent.; the amount of nitrogen, from 7 to 10 per cent. The sulphur of the bile is not oxidized into sulphuric acid, but it appears in sulphur-containing compounds in the urine. SECRETION OF BILE. The secretion of bile is not a simple nitration of already prepared materials from the blood through the liver, but a chemical production, attended with oxidation, of the characteristic biliary matters in the liver-cells, which exhibit histological change during the process of diges- tion, and to which the blood of the gland only supplies the raw material. It takes place continuously, the bile being in part temporarily stored in the gall-bladder, and only discharged in considerable amount at the time of digestion. The higher temperature of the blood in the hepatic veins, as well as the large amount of carbon dioxid in the bile, indicates the occurrence of oxidation-processes in the liver. Even the water of the bile is not simply filtered out, since the pressure in the biliary pas- sages may exceed that in the portal vein. It appears that the bile is derived from proteid only, and that the excretion of carbon dioxid in the act of respiration bears a certain relation to its production. In animals (birds) deprived of their livers the constituents of the bile are not produced. After an albuminous diet the liver-cells undergo increase in size, and in still greater degree after administration of carbohydrates, in connection with which they contain glycogen ; while after ingestion of fat they likewise become larger and contain fatty granules, principally at the periphery of the liver-lobules. Irritation of the celiac plexus causes reduction in the size of the cells, with deficiency in glycogen, and it appears to spur them on to secretion. The experiments of Kallmeyer and Jul. Klein, performed under the direction of Alex. Schmidt, have yielded the interesting result that a paste of fresh, "sur- viving" liver-cells produces the glycin and the taurin of the biliary acids from a mixture of hemoglobin (or serum) and glycogen (or dextrose) and that addition of soda or 0.6 per cent, sodium-chlorid solution favors this production. In addition to this production, a body resembling urea is formed. It is now established that the source of the latter is to be referred to the liver. Anthen, under Alex. Schmidt's direction, found that ''surviving" liver-cells possess the ability to take up dissolved hemoglobin in their cell-bodies, and, in the presence of glycogen, to transform this into a pigment closely related to the biliary coloring-matter. The Amount of Bile. Copemann and Winston found the amount of bile to be from 700 to 800 cu. cm. in twenty-four hours, in a small woman with a biliary fistula, in whom the common bile-duct was completely closed, so that no bile could flow into the intestine; Mayo Robson found the amount to be 862 cu. cm. in a similar case; Paton found it to be as much as 680 grams, with 2.2 per cent, solid matter. Older estimates are: 533 cu. cm. by v. !Wittich ; from 453 to 566 grams by Westphalen; 652 cu. cm. by Ranke, in 24 hours. Analogous estimates for animals are, to one kilogram of dog 32 grams (1.2 per cent, solid matter) one kilogram of rabbit 137 grams (2.5 per cent, solid matter); t of guinea-pig 176 grams (5.2 per cent, solids). The flow of bile into the intestine exhibits two maxima during a digestive period, one from the second to the fifth, and the other from the thirteenth to the fifteenth hour after the meal. The cause resides in reflex stimulation of the hepatic vessels, which in consequence become greatly distended with blood. 320 SECRETION OF BILE. The influence of the food is most striking. The most abundant secre- tion takes place after free ingestion of meat ; on addition of fat or carbo- hydrates scarcely any more is formed. In a state of hunger the quantity is reduced from one-third to one-half, and even more with a pure fat-diet. The ingestion of water increases the amount, with simultaneous relative reduction in the solid constituents. The influence of the circulation. The portal vein furnishes especially the material for the production of the bile, and in greater degree than the hepatic artery. The latter is at the same time the nutrient vessel of the tissues of the liver. This is shown by the following observations : (a) Simultaneous ligation of the hepatic artery (diameter, 5^ mm.) and of the portal vein (diameter, 16 mm.) abolishes the secretion of bile. (b) If the hepatic artery is ligated, the portal vein alone maintains the secre- tion. According to Kottmeier, Betz, Cohnheim and Litten, ligation of the artery or of one of its branches is said, further, to result in necrosis of the parts supplied, and possibly of the entire liver, as the artery is the nutrient vessel of this organ. After ligation of the artery the production of urea diminishes greatly; while after ligation of the portal vein this is said to remain almost normal. (c) If the branch of the portal vein for a lobule of the liver is ligated, only slight secretion takes place in this lobule through the agency of the artery. Thus neither exclusive ligation of the hepatic artery nor exclusive gradual obliteration of the portal vein (rarely observed as a morbid condition) results in cessation of the secretion. Only diminution in the secretion takes place. The observation that the secretion ceases after sudden ligation of the portal vein (which, besides, is rapidly fatal) is to be explained by the fact that, in addition to the diminution in the secretion, the enormous blood-stasis in the abdominal viscera after this operation makes the liver intensely anemic and therefore unsuited for secretion. (d) If the blood of the hepatic artery is introduced directly into the lumen of the opened portal vein, ligated peripherally, the secretion continues. (e) The passage as rapidly as possible of large amounts of blood through the liver acts most favorably upon the secretion. In this connection the pre- vailing blood-pressure is not of primary importance, for after ligation of the in- ferior cava above the diaphragm, in consequence of which the highest degree of blood-pressure due to stasis develops, the secretion ceases. The transfusion of considerable quantities of blood always increases the production of bile, although excessive pressure in the portal vein, from the introduction of blood from the carotid artery of another animal restricts the production. (f) Profuse loss of blood has a tendency to cause cessation of bile-production before the function of the muscular and nervous apparatus is abolished. A more abundant blood-supply to other organs, as, for example, to the muscles of the body engaged in hard labor, diminishes the secretion. (g) The influence of the nerves. All procedures that cause contraction of the arteries of the abdomen, such as irritation of the valve of Vieussens, of the inferior cervical ganglion, the hepatic nerves the splanchnic nerve, the spinal cord, whether directly, as by strychnin, or reflexly, by irritation of the sensory nerves, diminish the secretion. All procedures that induce stagnation of blood in the hepatic vessels, such as division of the splanchnic nerves, diabetic puncture, divi- sion of the cervical cord, have a like effect. Paralysis (ligation) of the hepatic nerves is said at first to increase the secretion of bile, with reddening of the liver. (h) With regard to the raw material brought to the liver by the blood-vessels for the production of bile, the difference in the composition of the blood in the hepatic veins and that in the portal vein is noteworthy. The blood in the hepatic veins contains somewhat more sugar, lecithin, cholesterin, and blood-corpuscles, but, on the contrary, it is deficient in albumin, fibrin, hemoglobin, fat, water and salts. The liver is capable of excreting unchanged in the bile biliary pigments circulating in the blood. The production of bile is dependent preeminently upon the trans- formation of the red blood-corpuscles, as they furnish the material for the formation of some of the constituents. EXCRETION OF BILE. 321 All procedures, therefore, that induce increased destruction of red blood- corpuscles make the liver rich in hemoglobin and, as a result, cause increased production of bile, also pathologically, as, for example, in the presence of malaria and blood-degenerations. Naturally, a normal condition of the liver-cells is necessary for normal secretion. For observing the secretion of bile in animals, a biliary fistula is established, the fundus of the gall-bladder being opened somewhat to the right of the xiphoid process, and then being sutured into the abdominal wall, with the aid of a cannula kept constantly open. As a rule, all of the bile will then be discharged externally. If absolute certainty in the latter connection be desired, the common bile-duct should be ligated in two places and divided. Soon after the establishment of a fis- tula, the secretion of bile diminishes. This is dependent upon the removal of the bile from the body. Introduction of bile in the body from some other source again increases the secretion. Various investigators have been able to observe directly biliary fistulas developed pathologically in human beings. In dogs regeneration of the divided bile-duct may take place. EXCRETION OF BILE. This takes place : 1. Through the constant advance of fresh amounts of bile from the seat of production toward the excretory ducts. 2. Through the periodic compression of the liver by the diaphragm from above, with each inspiration. In addition, each inspiration accel- erates the blood-current in the hepatic veins ; each respiratory increase in abdominal pressure hastens the blood-current in the portal vein. Whether the diminution in the secretion of bile following bilateral division of the pneumogastric nerves is to be explained in this manner has been decided in the affirmative. Nevertheless it is to be borne in mind that the pneumogastric nerve sends branches to the hepatic plexus. Whether the excretion of bile is also decreased after paralysis of the phrenic nerves and relaxation of the abdom- inal pressure is undetermined. 3. By the peristaltic contraction, every fifteen or twenty seconds, of the unstriped muscle-fibers of the large biliary ducts and the gall-bladder, the secretion is forced onward. Stimulation of the region of the spinal cord, from which the motor nerves for these structures are derived (through the splanchnic nerves), for this reason induces acceleration of the discharge, which is later followed by retardation. Under normal circumstances this stimulation appears to be due to reflex action, ex- cited by the entrance of the ingesta into the duodenum, in conjunc- tion with stimulation of the movement of this portion of the intestine. The movement of the biliary ducts can be in part excited, in part inhibited reflexly by stimulation of the central end of the pneumogastric or of the sciatic nerve. According to Oddi, the common bile-duct is provided with a sphincter at its duodenal orifice, which is affected by reflex influences: gastro-intestinal irritation is believed to cause spastic contraction, which would not be unimportant in the explanation of attacks of jaundice of nervous origin. 4. Direct stimulation of the liver or reflex stimulation of the spinal cord retards the excretion. On the other hand, extirpation of the hepatic plexus, as well as injury to the floor of the fourth ventricle, has no dis- turbing influence. The splanchnic nerve is the motor nerve of the bile- ducts and the gall-bladder. Stimulation of its central extremity causes relaxation of ducts and bladder, while stimulation of the central end of the pneumogastric nerve causes their contraction, together with relaxa- tion of the sphincter of the duodenal orifice. 322 RESORPTION OF BILE. 5. Stasis of bile occurs in the bile-ducts even from relatively slight resistance. A manometer fastened in the gall-bladder of a guinea-pig balanced a column of water more than 200 mm. high. Up to this pressure, therefore, secretion took place. If this pressure were increased or maintained for an excessively long time, absorption of the water of the bile into the blood took place on the part of the liver, up to about four times the weight of the liver, as a result of which solution of red blood-corpuscles by the bile absorbed took place at the same time, with the passage of hemoglobin into the urine. Various substances that enter the circulation readily pass over into the bile, particularly the metals, which are also deposited in the hepatic tissue. Further, potassium iodid, bromid, and ferrocyanid, potassium chlorate, arsenic, oil of turpentine, bile injected into the blood (also that from other animals), indigo- carmine and xanthophyllin pass over; less readily, cane-sugar and grape-sugar, sodium salicylate and carbolic acid. Sugar has been found in cases of diabetes, leucin and tyrosin in cases of typhoid fever, altered hemoglobin in the presence of blood-degeneration, lactic acid and albumin under other pathological con- ditions. Some substances promote the secretion of bile, olive-oil most intensely; further, oil of turpentine, sodium salicylate, alkalies and laxatives, bile and salts of the biliary acids (particularly from other species of animals), which, after ab- sorption, are again secreted by the liver. Pilocarpin and atropin diminish the secretion. The so-called lymphagogues induce marked secretion of bile in conse- quence of increased hepatic activity; the increase of lymph, on the part of the liver, is thought to depend upon the latter. RESORPTION OF BILE. Symptoms of Jaundice (Icterus; Cholemia). If an obstruction occurs to the dis- charge of bile into the intestine, as, for example, a plug of mucus or a gall-stone occluding the common bile-duct, or a tumor or pressure from without, rendering the duct impervious, the biliary passages become distended, and, through their distention, cause enlargement of the liver. The pressure in the biliary passages is naturally increased under such conditions. As soon as this pressure has reached a certain point, in the dog up to 275 mm. of a column of the excreted bile as must soon take place with the continued production of bile resorption of the bile from the greatly distended bile-ducts of larger size into the lymph-vessels (not into the blood-vessels) of the liver occurs. In this way the biliary acids and the biliary coloring-matter enter the blood. Ligation of the thoracic duct therefore prevents the entrance of the substances into the blood. Also when the pressure within the portal vein is abnormally low, it is thought that bile can pass over into the blood without occlusion of the bile-ducts. This is said to be partly the case in the presence of icterus neonatorum, as blood no longer enters the portal vein from the umbilical vein after the umbilical cord has been tied; further, in the presence of the " hunger - icterus " observed during the state of hunger, as in the stage of inanition, the distribution of the portal vein is relatively empty, on account of deficient absorption from the intestine. Cholemia may, however, result also from the excessive production of bile (hypercholia) , which cannot be completely discharged into the intestine, and thus is resorbed. This takes place when erythrocytes, which furnish the material for the manufacture of the bile, are destroyed in excessive amount. From this material only the liver can elaborate bile. Under such circumstances a plug of inspissated secretion at times forms in the bile-ducts, as a result of which, in consequence of the stagnation of the bile, its resorption is in turn favored. The transfusion of heterogeneous blood acts in this way, in consequence of destruction of the red blood-corpuscles. Therefore icterus is a frequent symptom under such conditions. The author has encountered the same phenomenon after excessive transfusion of blood from the same species, the blood being in part likewise dis- solved later. Such a solvent effect upon the erythrocytes is exerted also by the injection of some heterogeneous sera, of salts of the biliary acids, of water, of vari- ous acids, as, for example, phosphoric acid, and by the administration of large amounts of chloral, chloroform, and ether. Further, injections of hemoglobin in solution into the blood-stream or into the intestine, from which it is absorbed, have the same effect. (The subject is further considered on p. 34 1 .) RESORPTION OF BILE. 323 If, as a result of compression of the placenta in the uterus, too much blood has been carried to the new-born infant, a portion of this excess of blood in the body may be dissolved during the first days of life, the hemoglobin being trans- formed into bilirubin, with symptoms of icterus. Under such circumstances also there is excessive destruction of erythrocytes, as, indeed, of all of the tissues, because in the new-born infant, with insufficient nourishment the metabolic processes must be more active for the maintenance of respiration, heat-production and digestive activity. The jaundice that is exemplified by the foregoing symptoms is also designated hepatogenic, or resorption-icterus, because it is due to the absorption of bile already prepared in the liver. Cholemia is accompanied by a series of characteristic symptoms: 1. Biliary coloring-matter' and the biliary acids enter into the tissues of the body, giving rise to the most striking objective symptom (and therefore designated also jaundice). The external integument, particularly the sclera, ac- quires an exquisitely yellow color. In pregnant women the fetus also is discolored. Hematoidin-crystals have been found in the kidneys, the blood and the fatty tis- sue of icteric children. In exceptionally rare cases, as in the presence of hemi- plegia, only one-half of the body has been found jaundiced. 2. The biliary acids and the biliary coloring-matters appear in the urine, though not in the saliva, the tears or in mucus. When the coloring-matter is present in large amount the urine acquires a deep yellowish-brown color, while its foam is intensely lemon-yellow. Immersed strips of paper or linen are stained the same color. Occasionally crystals of bilirubin are present. 3. The feces become clay-colored, because of the absence of hydrobilirubin derived from the bile-pigment; extremely hard, because the diluting bile does not reach the intestine; rich in fat, because the fats, particularly the more solid, are not sufficiently digested in the intestine in the absence of bile (so that even as much as 78 per cent, of the fat ingested passes out in the feces; principally fatty acids and soaps appear in the feces, and but little neutral fats) ; and highly offensive, because, under normal conditions, the bile poured out into the intestine inhibits putrid decomposition of the intestinal contents. The evacuation of the feces takes place sluggishly, partly on account of their hardness, partly because of the absence of bile, which excites peristaltic movements in the intestines. 4. The heart-beats are reduced to about 40 in the minute. This is due to the salts of the biliary acids, which at first stimulate the heart and then enfeeble it. Injection of the salts of the biliary acids into the heart causes, therefore, at first, transitory increase in the heart-beats, followed by slowing. The same result is brought about if these substances are injected directly into the blood, although under such circumstances the brief stage of stimulation is much less marked. Division of the pneumogastric nerve has no influence on this phenom- enon. In addition to the action on the heart, there is marked dilatation of the smallest blood-vessels, slowing of the respiration and lowering of the tem- perature. 5. An influence on the nervous system, either through the salts of the biliary acids or through the cholesterin accumulated in the blood, perhaps also upon the muscles, is shown by the great general relaxation, fatigue, weakness and somnolence, finally deep coma; at times by insomnia, pruritus, even delirium and convulsions. In experiments on animals Lowit observed symptoms, after injections of bile, indicative of stimulation of the respiratory, cardio-inhibitory and vasomotor centers. Direct application of bile or its salts to the cerebrum causes convulsions. 6. Jaundice of marked degree is attended with yellow vision, in consequence of impregnation of the retina with yellow biliary coloring-matter. 7. The biliary acids in the blood dissolve the erythrocytes, and this leads to the further formation of bile. The dissolved hemoglobin is transformed into new bile-pigment, while the globulin-body of the disintegrated hemoglobin mav form casts in the renal tubules, which later are washed into the urine. Should dissolution not take place, the erythrocytes become swollen and exhibit increased solubility. After ligation of the bile-duct, the protoplasm of the liver-cells disappears, and according to some observers partial necrosis of the hepatic tissue occurs, with secondary reactive inflammation, connective-tissue hyperplasia. cell-multiplica- tion of the epithelial cells of the biliary passages. The stagnating bile diminishes in amount and exhibits further an increase of mucus and cholestenn, but on the other hand a reduction in taurocholic acid (in the dog)- 324 ACTION OF THE BILE. ACTION OF THE BILE. The bile is a metabolic product largely destined for excretion, and participating in but small measure in the digestive process. Bile plays an important part in the absorption of fat. It forms a fine emulsion of the neutral fats, in consequence of which the fatty granules, in addition to chemical division, are especially rendered capa- ble of passing through the cylindrical epithelium of the small intes- tine. It does not effect the chemical decomposition of the neutral fats into glycerin and fatty acids, as does the pancreatic juice, but it is capable of dissolving the fatty acids through the salts of the biliary acids. The soaps present in the intestine are soluble in the bile and are capable in turn of greatly increasing the emulsifying power of the bile. The bile itself, however, is capable of converting the fatty acids directly into an acid solution that exerts an active emulsifying influence. As the bile, like a soap solution, bears a certain relation to aqueous fluids as well as to fats, it may conduce to diffusion between the two, as the membrane can be moistened and can imbibe both fluids. From the foregoing it follows that the bile is of great importance for the preparation and absorption of fats. This can also be demonstrated by experi- ments on animals, in which the bile is entirely conveyed externally through a fistula. Dogs thus treated absorb, at the most, 40 per cent, of the fat ingested, while normal dogs absorb 99 per cent. The chyle of such animals is, accord- ingly, deficient in fat, and is not white, but transparent. The feces, however, contain more fat and are greasy. The animals eat greedily; the tissues of the body show great deficiency of fat, even when the nutrition in general has not suffered much. In human beings suffering from derangement in the secretion of bile, a diet rich in fat is, for this reason, contraindicated. Fresh bile contains some diastatic ferment, as starch and glycogen are converted into sugar. This ferment is, however, absorbed from the walls of the alimentary canal and is then excreted as ptyalin by the bile, as by the urine also. The bile acts as a stimulant to the intestinal musculature and thus contributes to absorption in general. Perhaps through its biliary acids, acting as irritants, it causes the muscles of the intestinal villi to contract from time to time, in consequence of which these propel the contents of their lymph-spaces into the larger lymph-trunks, and thus are capable of absorbing renewed amounts. Also the musculature of the intestinal wall itself appears to undergo excita- tion, probably through the agency of the myenteric plexus. In favor of this view is the fact that intestinal peristalsis is greatly impaired in animals with biliary fistulas and in the presence of obstruction of the biliary passages, as well as the fact that the salts of the biliary acids, administered by the mouth, cause diarrhea and vomiting. As, however, intestinal contractions aid absorption, the bile is, in this connection also, active in taking up the dissolved food. The presence of bile is necessary for the normal vital activity of the intestinal epithelium in the absorption of the fatty globules. Through its excretion the bile supplies a sufficient amount of water for the feces. Animals with biliary fistulae and human beings with obstructed biliary passages are markedly constipated. Besides, the slippery mucus of the bile facilitates the advance of the ingesta through the intestinal canal. FINAL FATE OF THE BILE IN THE INTESTINAL CANAL. 325 The bile diminishes putrefactive decomposition of the intestinal con- tents, especially with a fatty diet. On the entrance of the strongly acid gastric contents into the duo- denum, the glycocholic acid is precipitated by the acid of the stomach and carries the pepsin with it. Further, the albumin and the gelatin, still in solution, but not the peptones and propeptones, are precipitated by the taurocholic acid, salts of the biliary acids having already been de- composed by the acid of the stomach. If, however, the mixture is again rendered alkaline by the pancreatic and the intestinal juice and the alkali of the bases derived from the salts of the biliary acids, the pancreatic ferments enter energetically into action. If bile enters the stomach, as, for instance, in the act of vomiting, the acid of the gastric juice combines with the bases of the salts of the biliary acids. There thus results principally sodium chlorid and free biliary acids. At the same time the acid reaction is diminished. The biliary acids are not effective as acids in gastric digestion, in place of the combined hydrochloric acid, the neutralization causing also precipitation of the pepsin and the mucin. As soon, however, as the wall of the stomach secretes additional acid, the pepsin is again dissolved. The bile entering the stomach has a disturbing effect on gastric digestion also, by causing contraction of the albuminates, as these can be peptonized only when swollen. FINAL FATE OF THE BILE IN THE INTESTINAL CANAL. Of the constituents of bile, some are evacuated with the feces, while others are again absorbed through the intestinal walls. The mucin passes into the feces unchanged. The biliary coloring-matters are mostly reduced in the large in- testine and are partly evacuated with the feces as hydrobilirubin ; a small portion of them is absorbed and finds its way into the urine as urobilin. The reduction may proceed beyond the formation of hydro- bilirubin to that of a colorless material, which may, however, upon ad- mission of oxygen, be again oxidized to hydrobilirubin. Hydrobilirubin is absent from meconium, but bilirubin and biliverdin are present together with an unknown red oxidation-product derived from them. Therefore the process that takes place in the fetal intestine is not a reducing but an oxidizing one. Cholesterin is in part evacuated with the feces; in part it is re- duced to the form of hydrocholesterin (coprosterin), crystallizing in needles. The biliary acids are, for the most part, again absorbed through the walls of the jejunum and the ileum, and are utilized anew in the pro- duction of bile. Tappeiner found them in the thoracic duct; small amounts find their way from the blood into the urine. Only a small portion of glycocholic acid appears unchanged in the feces. Taurocholic acid, in so far as it is not absorbed, is readily decomposed in the intestine by putrefactive processes into cholic acid and taurin. The former is found in the feces, the latter is not infrequently absent. Cholic acid is, however, in part resorbed and may again unite in the liver with glycin or taurin. As putrefactive decomposition is absent from the fetal intestine, unchanged taurocholic acid is accordingly present in the meconium Grlycocholic acid, when administered, is found again in the bile from animals (< mally excrete but little thereof. The feces certainly contain merely traces of lecithin. 326 THE INTESTINAL JUICE. As, therefore, the largest part of the biliary acids is returned to the blood, it is clear that animals from which all the bile is lost through a biliary fistula, without their licking it up, lose considerably in weight. This is due partly to the impaired digestion of fat, in part to the direct loss of the biliary acids. If dogs are nevertheless to maintain the same weight, they must consume almost double their former nourishment. Under such conditions, carbohydrates are especially serviceable as a substitute for fat in the diet. If their digestive ap- paratus is in other respects intact, the animals may, by reason of their voracity, even gain in weight. Under such circumstances, however, it is the muscles almost alone and not the fat that is increased. The fact that bile is secreted during fetal life, while none of the other digestive fluids are produced, indicates that the bile is in part a product of retrogressive tissue-metamorphosis, and is intended for the constant elimination of certain excrementitious matters. The cholic acid, which is absorbed through the intestinal wall, is finally burned up in the body into carbon dioxid and water. The glycin gives rise to the production of urea, as well as hippuric acid, as, after the ingestion of that substance, the amount of urea is greatly increased. The fate of the taurin is not known. Considerable amounts administered to human beings by the stomach appear 'again in the urine principally as taurocarbamic acid, together with a small amount of unchanged taurin. When injected subcutaneously into a rabbit, it almost all appears in the urine. THE INTESTINAL JUICE. The human intestine is ten times as long as the length of the body from the vertex to the anus. In this it resembles that of fructivorous apes. It is relatively longer than that of omnivora. Its minimum length is 507 cm.; its maximum length, 1149 cm. Its capacity is relatively greatest in children, in whom also it is relatively longer. The intestine is somewhat longer in males than in females. The intestinal juice is the digestive fluid secreted by the numerous glands of the intestinal mucous membrane. The largest amount is fur- nished by Lieberkuhn's glands; the duodenum receives, besides, the scanty secretion of the compound alveolar grands of Brunner. B runner's glands, which occur singly in human beings, but in the sheep constitute a continuous layer in the duodenum, are present, in part, at the pylorus. Their cylindrical cells have a middle, darker zone'; the flat nucleus lies near the base of the cell, with a diplosome nearer its free surface. During the state of hunger, the cells are turbid and small, and, like the pyloric glands of the stomach, they contain fatty granules, while during digestive activity they are large and clear. The glands contain nerve-filaments from Meissner's plexus in the mucous membrane. The Secretion of Brunner' s Glands. The usually granular contents of the secretory cells consist, in addition to albuminous materials, of mucin and ferment-substances of unknown nature. It is not improbable that these glands are related to the pancreas, and perhaps are even to be regarded as detached portions of the pancreas. Their activity seems to favor this view. An aqueous extract (i) dissolves albumin slowly and feebly, at the temperature of the body. (2) It possesses diastatic activity. The secretion appears to have no effect on fats. It should be especially emphasized that, as on account of the small size of the glands they must be viewed individually, \vith a magnifying glass, from the under surface of the intestinal mucous membrane, digestive experiments are exceedingly difficult. Lieberkuhn's crypts or glands are simple tubular glands, resembling the finger of a glove, that lie close to one another in the intestinal mucous membrane, and in greatest number in that of the large intestine (on account of the absence of villi). They possess a membrana propria, constituted of most delicate fibrils, THE INTESTINAL JUICE, 327 and a single layer of cylindrical protoplasmic cells, between which goblet-cells also occur, in small number in the small, and in large number in the large intes- tine. The glands in the small intestine yield a watery secretion principally; those of the large intestine, from their numerous goblet-cells, ropy mucus. Both kinds of gland-cells multiply by mitosis, and the new products move from situ- ations where active division is going on to places where the production is less active. The mucus in the goblet-cells encloses usually a single central body. The secretion of Lieberkiihn's glands is, from the duodenum down- ward, the chief source of the intestinal juice. The intestinal juice is obtained, by Thiry's method, in the following manner: From a loop of the in- testine of a dog, withdrawn from the abdomen, a piece of the length of a hand is so divided by two inci- sions that only the continuity of the intestinal canal is severed but not the mesentery. Then one end of this piece is ligated; the other, left open, is sutured in the abdominal wound, after the ends of the intestine, be- tween which the piece has been re- moved, have been carefully united by suture. Vella permits both ends of this horseshoe-shaped portion of intestine to open on the abdominal wall. In this way, after the opera- tion has been completed, the animal can continue to live with its but slightly abbreviated intestine. The intestinal fistula, with a free exter- nal opening, yields, however, an in- testinal juice that is not contamin- ated by any other digestive secretion. The intestinal juice derived from such a fistula flows spon- taneously in very small amount ; during digestion it is largely increased. Mechanical, chemi- cal and electrical stimulation increase the secretion, especi- ally of mucus, with reddening of the mucous membrane, so that 100 square centimeters yield from 13 to 18 grams of juice in an hour. The adminis- tration of pilocarpin also in- creases the secretion. The juice is light yellow in color, opal- escent, watery, strongly alkaline, effervescing on addition of acids, and has a specific gravity of 1010. It contains, in human beings, proteid (0.80 per cent.), ferments, mucin, especially in the large intestine (0.73 per cent.), and salts (0.88 per cent.), of which 0.34 per cent, is soda and 0.5 per cent, sodium chlorid. The amount of intestinal juice secreted is least with the presence of dissolved grape-sugar in the intestines, greater with the presence of cane-sugar, and still greater with the presence of starch and peptone. It increases in the second hour of digestion. G. FIG. 120. Longitudinal Section through the Small Intestine of a Dog: B, connective-tissue layer; Z, intestinal villi covered with cylindrical epithe- lium; L, Lieberkiihn's glands; Mm, muscularis mucoss; G, crowded lymph-follicles; Me, circular muscular layer; Ml, longitudinal muscular layer. 328 THE INTESTINAL JUICE. Biedermann found the production of mucus in the goblet-cells of the intestine, in the frog, to take place in such a manner that droplets of mucus first appear in the cell-contents. These enlarge into vacuoles, which soon become confluent; then the mucus escapes from these and is discharged from the cell. The digestive activity of the juice of the small intestine is still in many respects unexplained. The juice has been found most active in the dog, while it is more or less inactive in other animals. It possesses less diastatic activity than the saliva and the pancreatic juice. It forms maltose, which rapidly passes over into dextrose. The glands of the large intestine are said to be wanting in this property, von Wittich has extracted the ferment by means of glycerin diluted with water. The intestinal juice is capable of transforming maltose into grape- sugar. It, therefore, continues the diastatic action of the saliva and the pancreatic juice, which principally are active only up to the pro- duction of maltose. According to Bourquelot, this action is due to intestinal bacteria, and not to the intestinal juice as such, nor to the saliva, the gastric juice or the invertin. The larger part of the maltose, however, seems to undergo absorption unchanged. No action upon proteids is recognizable, or, at least, only traces. The peptonizing properties described are in part dependent upon putre- factive processes. According to earlier statements, fibrin is slowly peptonized by trypsin and pepsin; albumin, fresh casein, raw or cooked meat and vegetable albumin less readily. Gelatin is probably also brought into solution by a special FIG. 121. Transverse Section through Lieber- ferment. kuhn's Glands: H, cavity of the glandular The intestinal JU1C6 is Capable of tubule; D, glandular epithelium; B, connec- . % . - . . ... tive tissue; G, blood-vessels. acting on tat, which it partially emulsifies in the presence of free acid. Whether the neutral fats are also decomposed, in small measure, has not as yet been determined with certainty. The intestinal juice contains invertin, an unorganized ferment, which decomposes disaccharids (cane-sugar, milk-sugar and maltose) into monosaccharids (dextrose, levulose and galactose), with the taking up of water and the production of heat : C 12 H 22 O n 4- H 2 = C 6 H 12 6 + C 6 H 12 6 Cane-sugar + Water = Dextrose Levulose. Milk (casein) is coagulated. With regard to the ferments of the alimentary canal, Langley upholds the view that they undergo destruction: the diastatic ferment of the saliva is de- stroyed by the hydrochloric acid of the gastric juice ; pepsin and the rennet-ferment succumb to the action of the alkaline salts of the pancreatic and intestinal juices and the trypsin; the diastatic and peptic ferments of the pancreas are rendered inert by the acid fermentation in the large intestine. Nevertheless some ferment is absorbed and passes over into the urine. Of the influence of the nerves upon the secretion of the intestinal juice but little has been ascertained with certainty. Stimulation or division of the pneumo- gastric nerves is without apparent effect. On the other hand, destruction of the nerve-filaments passing to the intestinal loops and accompanying the blood-ves- sels is followed by distention of the intestinal canal with an abundance of watery BACTERIAL FERMENTATION IN THE INTESTINES. 329 fluid. This result is explained in part by paralysis of the vasomotor nerves of the intestinal tract. As the nerve-filaments for a limited portion of intestine, ligated in two places, can be completely separated, the watery intestinal contents will be found only in the corresponding loop of intestine. According to Hanau, the condition in this experiment of Moreau is one of paralytic secretion, which, with regard to time, pursues a typical course. The following substances are after ingestion excreted by the intestinal mucous membrane of isolated fistulas : iodin, bromin, lithium, metallic ferrocyanogen, salts of iron and others. FERMENTATIVE PROCESSES IN THE INTESTINES DUE TO MICROBES; INTESTINAL GASES. Wholly different from the peculiar digestive processes just described, which are brought about by definite unorganized ferments or en- zymes, are those processes which are to be considered as fermentative or putrefactive decompositions. These are caused by microbes, the so- called excitants of fermentation or putrefaction, or organized ferments; and they may, therefore, take place outside of the body, in suitable media. Lower forms of organisms, which maintain fermentative pro- cesses in the intestinal tract, are often swallowed with food and drink, as well as with the buccal fluid. Upon the introduction of these the processes of decomposition begin, with simultaneous production of gas. On a pure milk-diet intestinal putrefaction is much less marked. Fermentation, therefore, cannot occur in the intestine during fetal life. For this reason gases are always absent in the intestine of the new-born. The first bubbles of air reach the intestine through frothy saliva swallowed, even before food is taken. As, however, micro- organisms may enter the intestinal tract with the air swallowed, the development of gas by fermentation must soon follow. The development of the intestinal gases thus goes hand in hand with the fermentative processes. As, however, gases from the air swallowed are exchanged in the intestinal canal, the composition of the intestinal gases will be found to be dependent upon various factors. Kolbe and Ruge collected intestinal gases from the human anus and found in 100 volumes: Food. C0 2 . H. CH4. H,S. Milk ................. 16.8 43-3 -9 Meat ................ -.4 ai Peas ................. 21.0 4.0 55.9 3.3 ) 18.9 ) Moreover, it should be noted: i. That oxygen is rapidly absorbed by the walls of the canal from the air-bubbles swallowed with the food, so that, in the lower part of the large intestine, even traces of oxygen are absent. In exchange the blood-vessels of the intestinal wall give up into the intestine carbon dioxid, so that, therefore, a portion of the car- bon dioxid in the intestines is derived from the blood by diffusion. 2. Hydrogen, carbon dioxid and ammonia, as well as marsh-gas, are also developed from the intestinal contents by fermentation, which may take place even in the small intestine. Bacteria as Excitants of Fermentation. The organisms that especially cause fermentation, putrefaction and other forms of decomposition are bacteria (schizo- mycetes), namely, minute, unicellular structures, chiefly having the shape < sphere (micrococcus) , or a short rod (bacterium) , or a long rod (bacillus) , or a spiral thread (vibrio, spirillum, spirochasta) . Their power of reproduction is beyond all conception. Through their vital phenomena they cause profound 330 BACTERIAL FERMENTATION IN THE INTESTINES. chemical changes in the matters containing them. As for their growth and metabolism, they abstract certain substances from the nutritive fluid in which they live, they decompose the chemicals contained therein. In this process some of them form certain substances that may subsequently act as ferments upon matters in the nutritive fluid. The microbes are destroyed by antiseptics, such as carbolic acid, salicylic acid, etc., although the ferments are not destroyed. Therefore, these substances afford a means of distinguishing and separating the fermentative from the micro- biotic decompositions. The bacteria consist of a capsule and protoplasmic contents. Some possess flagella as organs of locomotion, which, perhaps, are possessed by all capable of motion. The organisms multiplying by division are sometimes collected together in extensive colonies, united by a gelatinous mass, often visible to the naked eye, and which are designated zoogleae. These appear in the form of nodules, branches, patches, flakes, layers of mold, or ropy, creamy or greasy deposits. In the case of some micro-organisms, principally bacteria, multiplica- tion takes place by spore-formation, especially if the nutritive fluid becomes deficient in nutrient material. The rods then grow into threads of considerable size, which become jointed; and globular, strongly refractive granules, from i to 2 /u in size, develop in the individual parts (Fig. 122, 8, 9). In the case of some, as FIG. 122. A, bacterium aceti, in the form of cocci (i), diplococci (2), short bacilli (3), and jointed threads (4, 5). B, bacillus butyricus: i, isolated spore; 2, 3, 4, germinating stage of the spore; 5, 6, short and long bacilli; 7, 8, 9, spore-formation in the bacteria. the butyric-acid germ, the bacilli, before spore-formation, acquire the shape of an enlarged spindle, within which the spores form. After death of the mother- cells, the spores become free, and from them, transplanted to a suitable soil, the newly formed cells of the microbes again germinate. The processes of spore- formation (7, 8, 9) and of germination of the butyric-acid micro-organism (1,2, 3, 4) are illustrated in Fig. 122, B. The spores are extremely resistant, being capable, in the dry state, of surviving for a long time, and some even withstanding boiling. Among bacteria, a distinction is made between those that exhibit their vital activity in the presence of oxygen, aerobes, and others that thrive only when oxygen is excluded, anaerobes. In accordance with the products to which they give rise by decomposition in their nutrient media, they may be divided into those that induce decomposition in the form of fermentations (zymogenic schizo- mycetes) , those that form pigments (chromogenic) , those that generate bad odors, as in the putrefactive processes (bromogenic) , and, finally, those that, developing in the living tissues of other organisms, cause morbid conditions, even death itself (pathogenic) . Some also elaborate poisons (toxicogenic) . All of these have been found in and upon the human body. If it be borne in mind that a large number of bacteria are introduced into the alimentary canal with foods and drinks, as well as, in part, also with the in- spired air; that, further, the temperature of the intestine is especially favorable BACTERIAL FERMENTATION IN THE INTESTINES. 331 to their development ; and, finally, that sufficient material of the most varied kind not entirely disposed of by the digestive processes, furnishes nutrient matter for the vegetation of the germs, it is not surprising that a rich formation of these organisms is found in the alimentary canal and that they cause numerous forms o decomposition in the intestinal contents. Knowledge of these processes is at the present time, still highly deficient; and the formula* proposed for the de- compositions can, therefore, only approximately explain the processes. For this reason, the following statements can only be considered provisionally as aphorisms in the study of the mycotic intestinal decompositions. Fermentation of Carbohydrates, which takes place principally in the small intestine, i. Bacillus acidi lactici (bacterium lacticum), whose biscuit-shaped ^ cells, from 1.5 to 3 /^ in length, are arranged in groups or rows or are isolated, causes fermentative decomposition of sugar into inactive lactic acid : C 6 H 12 6 2(C 3 H 6 3 ) i Grape-sugar = 2 Lactic acid. Milk-sugar (C 12 H 22 O n ) may be decomposed by the same bacterium, with the addition of water, first into two molecules of grape-sugar, 2(C 6 H 12 O 6 ), and this in turn into four molecules of lactic acid, 4(C 3 H 6 O 3 ). This micro-organism, whose germs float in the air everywhere, causes the spontaneous souring and curdling of milk. It develops further in sour-crout, sour pickles, and the like. It induces fermentation of cane-sugar, mannite, inosite, and sorbite, as of the sugars mentioned. In addition to lactic acid, carbon dioxid also results. There are, besides, other lactic-acid-producing bacteria that are capable further of transforming starch into sugar, van de Velde obtained lactic, butyric and succinic acids as products of the fermentative activ- ity of the bacillus subtilis (Fig. 123), and mannite as a reduction-product. 2. Bacillus butyricus, which is often stained blue by iodin in a starch-containing medium, transforms lactic acid into butyric acid, together with carbon dioxid and hydrogen. 2(C S H 6 3 ) - C 4 H 8 2 + 2CO, + 4 H. 2 Lactic Acid = i Butyric Acid + 2 Carbon Dioxid + 4 Hydrogen. This bacterium (Fig. 122, B) is a true anaerobe, which vegetates only in the absence of oxygen. The lactic-acid bacillus, which actively consumes oxygen, is therefore its natural predecessor. Butyric-acid fermentation completes the transformation of many carbohydrates, chiefly starch, dextrin and inulin. It takes place constantly in the feces. There are a number of other bacteria with similar activity. The butyric-acid bacillus produces also dextrin from starch. 3. Certain micrococci are capable of developing alcohol as the chief product from sugar. In the human small intestine there are present besides: bacterium Bischleri (short rods) , which produces alcohol, inactive lactic acid and acetic acid from sugar; bacterium ilei (short rods), which transforms sugar into alcohol, succinic acid and some active paralactic acid, together with carbon dioxid and hydrogen; bacterium ovale ilei (almost spherical), which transforms sugar into alcohol, paralactic acid and traces of the fatty acids; bacillus gracilis ilei (delicate long rods), which has a similar action; bacterium lactis acrogenes, which transforms sugar into alcohol and succinic acid, together with lactic acid and some acetic acid. The presence of yeast also may result in the production of alcohol in the intestine, in both instances likewise from milk-sugar, which at first passes over into dextrose. Only traces are found in the intestine. 4. Bacterium aceti (Fig. 122, A) is capable, outside of the body, of transforming alcohol into acetic acid. C 2 H 6 + O = C 2 H 4 + H 2 Alcohol + Oxygen = Aldehyd Water. 332 BACTERIAL FERMENTATION IN THE INTESTINES. Aldehyd is changed by oxidation into acetic acid (C 2 H 4 O 2 ). Accord- ing to Nageli, the same micro-organism is capable of producing small amounts of carbon dioxid and water. As acetic fermentation ceases at 35 C., it will not take place in the intestine, so that the acetic acid con- stantly met with in the feces must result from other fermentative pro- cesses. Thus, it is produced in considerable amount in herbivora as a product of the fermentation of cellulose; being, after absorption, burned up in the fluids of the body. Acetic acid is formed also as a result of the putrefaction of albuminates with exclusion of air. 5. Also partial solution of starch and of cellulose is caused by schizo- mycetes (bacillus butyricus, bacterium termo, vibrio rugula) in the intestines; for cellulose, mixed with cloacal discharge or the intes- tinal contents, is transformed into a sugar-like carbohydrate, which then breaks up into equal volumes of carbon dioxid and marsh-gas. The neurin produced by the pancreas also yields marsh-gas (CH 4 ), in addition to carbon dioxid. The solution of the cellulose of the cell-walls then permits the action of the digestive juices upon the enclosed digestible portions of the n 34 FIG. 123. Hay-bacillus (Bacillus subtilis): i, spore; 2, 3, 4, germination of the spore; 5, 6, short bacilli; 7, jointed filament with spore-formation in each cell; 8, short bacilli, in part with spore-formation; 9, spores in individual short bacilli; 10, bacteria with flagella. vegetable food. In human beings the metabolism of cellulose is always slight, while in herbivora it is digested in considerable amounts. 6. Bacillus subtilis, cheese-spirilli and others are capable of trans- forming starch into sugar. 7. Micro-organisms (lactic-acid bacilli?) that produce invertin also occur in the intestinal canal. This substance can be obtained also from brewer's yeast by agitation with water and ether and subsequent fil- tration. Fermentation of Fats. Putrefaction is capable, with the aid of as yet unknown micro-organisms, of decomposing neutral fats into glycerin and fatty acids, after taking up water. Glycerin is susceptible of varied fermentations with different microbes, as, for example, the bacillus Fitzianus. When the reaction is neutral, hydrogen and carbon dioxid are formed, together with succinic acid and a mixture of fatty acids. Fitz observed alcohol, together with caproic, butyric and acetic acids, develop as a result of the action of the hay-bacillus (bacillus subtilis, Fig. 123), while in other cases butyl-alcohol principally resulted, van de Velde found butyric and lactic acids, together with traces of succinic acid, and also carbon dioxid, water and nitrogen. BACTERIAL FERMENTATION IN THE INTESTINES. 333 The fatty acids yield, chiefly as calcium-soaps, material suitable for fermentation. Calcium formate, in fermentation with cloacal discharge, yields calcium carbonate, carbon dioxid and hydrogen; calcium acetate yields calcium carbonate, carbon dioxid and marsh-gas. Of the oxy- acids, the fermentation of lactic, gly eerie, malic, tartaric and citric acids is known. According to Fitz, lactic acid, in combination with calcium, yields propionic acid, acetic acid, carbon dioxid and water. Valerianic acid in considerable amount is produced by other excitants of fermentation. Glyceric acid yields especially acetic acid, in addition to alcohol and succinic acid. Malic acid forms succinic acid and some acetic acid; as a result of other fermentative processes, propionic acid, and of still other fermentative processes, butyric acid, together with hydrogen; or it is decomposed into lactic acid and carbon dioxid. Tartaric acid breaks up into acetic acid, propionic acid, carbon dioxid and water; as a result of the action of other microbes, into butyric acid; and of that of still others, into acetic acid, together with some butyric and succinic acids and alcohol. Citric acid yields finally acetic, with some butyric and succinic acids. Fermentations of Proteids. In the fermentation of the undigested proteids in the intestine and their derivatives, which takes place princi- pally in the large intestine, micro-organisms likewise appear to take part. In the first place it should be emphasized that some schizomycetes are capable of producing peptonizing ferment, as, for example, the bacillus subtilis, bacillus liquefaciens ilei, the cheese-spirilli, the micro-organisms of pickled herring, etc., so that assistance to the peptic enzyme, even though slight, on the part of these microbes appears to be not wholly ex- cluded. It has been found that pancreatic digestion of albuminates does not proceed beyond the production of amido-acids : leucin, tyrosin and others. Putrefactive fermentation in the large intestine causes still further and more profound decompositions. Leucin (C 6 H 13 NO 2 ), by taking up two molecules of water, forms valerianic acid (C 5 H 10 O 2 ), ammonia, carbon dioxid and four molecules of hydrogen. Glycin behaves in a similar manner. Tyrosin (CgHuNC^) breaks up into indol (C 8 H 7 N), which is constantly encountered in the intestine, together with carbon dioxid, water and hydrogen. If the admission of oxygen is possible, still other decompositions take place. These products of putrefaction are wanting in the intestine of the fetus and the new-born. In the putrefactive de- compositions of proteids, as well as upon boiling them with alkalies, carbon dioxid and hydrogen sulphid develop, together with hydrogen and marsh-gas. Under such circumstances, gelatin yields, in addition to abundant leucin, much ammonia, carbon dioxid, acetic, butyric and valerianic acids and glycin. Mucin and nuclein undergo no decomposi- tion. Artificial digestive experiments with the pancreas disclose an extraordinary tendency to putrefactive decomposition. The body giving rise to the fecal odor, which likewise results from putre- faction, has not as yet been discovered. It is intimately related to indol and skatol, but these are odorless when prepared in the pure state. Among the solid matters in the large intestine produced only by putrefaction, indol (C 8 H 7 N) is especially to be pointed out. substance that results also from heating albuminates with alkalies, or in small amount by superheating them with water to 200 C. forerunner of indican in the urine. If the products of the digestion of albuminates, the peptones, are rapidly absorbed in the intestine, only a 334 BACTERIAL FERMENTATION IN THE INTESTINES. small amount of indol is formed. If, on the other hand, with a lesser degree of absorption, the putrefactive process can exert a profound effect chiefly upon the products of pancreatic digestion still present in large amount, considerable indol will be formed, and much indican subse- quently appears in the urine. Thus Jaffe found an abundance of indican in the urine in the presence of in- carcerated hernia and obstruction of the bowel. After transfusion with hetero- geneous blood, in connection with which the walls of the intestine are often the seat of extravasation of blood and thrombosis, and paralytic conditions of the intes- tinal vessels and musculature itself are not rarely encountered, the author has often found the amount of indican contained in the urine to be large. Test for indol: The fluid to be tested is acidulated with considerable hydrochlo- ric acid and is well shaken after addition of a few drops of oleoresin of turpentine. If an intense red color results, the pigment is removed by agitation with ether. The pigment resulting from fibrin in the process of tryptic digestion, and becom- ing violet with bromin-water, can be isolated by agitation with chloroform. In addition to the latter pigment, there is still a second pigment that passes over in the process of distillation, and can be extracted from the distillate by ether. Both appear to belong to the indigo-group. A. v. Bayer was able to produce indigo-blue artificially from orthonitrophenol- propionic acid by boiling with dilute sodium hydrate and after addition of some grape-sugar. From indigo-blue he obtained skatol, in addition to indol. G. Hoppe-Seyler observed an abundance of indican in the urine after feeding rabbits upon sodium orthonitrophenol-propionate. Further, some phenol (C 6 H 6 O) is formed in the intestine by the putre- factive process. Baumann observed the same substance as a result of the putrefaction of fibrin with pancreas outside of the body, and Brieger found it constantly in the feces. It appears to undergo an increase under conditions analogous to those attending an increase in the amount of indol, as an increase in the amount of indican in the urine is accompanied by an increase in the amount of phenyl-sulphuric acid. Amidophenyl-propionic acid also can be obtained from putrefying meat and fibrin as a product of the decomposition of tyrosin. Part of this is changed by putrefactive ferments into phenylpropionic acid (hydrocinnamic acid) , which is com- pletely oxidized in the organism to benzoic acid, and appears in the urine as hippuric acid. In this way is explained the formation of hippuric acid when a pure proteid diet is taken. Skatol (C 9 H 9 N, methylindol), a constant constituent of human feces, has been prepared artificially by Nencki and Secretan by protracted putrefaction of egg-albumin under water. In this way results skatol- carbonic acid, which, when heated, readily decomposes into skatol and carbon dioxid. Skatol also appears in the urine in combination with sulphuric acid. Milk inhibits the decomposition of albumin and intestinal putrefaction through the presence of casein and thus also diminishes the amount of ethereal sulphates in the urine. According to the brothers Salkowski, both skatol and indol result from a common substance preformed in albumin, which, when decomposed, at one time yields a larger amount of indol, and at another time a larger amount of skatol, accordingly as to whether the hypothetical indol-bacterium or the skatol-bac- terium active under such conditions prevails in the development. It is of great importance in the process of putrefactive fermentation whether this takes place with the exclusion of oxygen or not. In the former case reduc- tion occurs: oxy-acids are reduced to fatty acids, and there are developed, especially hydrogen, but also marsh-gas and hydrogen sulphid; the hydrogen, in turn, may cause further reduction. If, however, oxygen is still present, the nascent hydrogen divides the molecule of ordinary free oxygen into two atoms of active oxygen; there forms, thus, on the one hand, water, and on the other hand, the second atom of oxygen brings about active oxidation. PROCESSES IN THE LARGE INTESTINE. 335 The remarkable fact should yet be mentioned here that the putrefactive processes, after the development of phenol, indol, and skatol, and also of cresol, phenyl-propionic and phenylacetic acids, are again inhibited, and after a certain concentration in their production cease completely. Thus, the putrefactive pro- cess itself generates antiseptic substances even to the point of causing the death of the micro-organisms; for, as with highly organized beings, the excremen- titious products of the bacteria themselves are poisons for them. It is, there- fore, to be inferred that, in the intestinal canal also, the formation of the sub- stances mentioned in turn inhibits the putrefactive decompositions to some ex- tent. Ptomains are not formed normally in the intestines. The reaction of the contents of the small intestine is alkaline, due principally to carbonates, and in less degree to phosphates. The con- tents are, however, rich in carbon dioxid, the presence of which causes, on one hand, the acid reaction of the indicators reacting to carbon dioxid, while, on the other hand, it ensures the maximum efficiency on the part of the ferments in the intestine. In the large intestine' the reaction is generally acid, in consequence of the acid fermentation and decomposition of the ingesta and the feces. PROCESSES IN THE LARGE INTESTINE. FORMATION OF THE FECES. Within the large intestine the putrefactive and fermentative decom- positions of the ingesta greatly exceed the fermentative or true digestive transformations, as only small amounts of the ferments of the intestinal juice are found in it. In addition, the absorptive activity of the walls of the large intestine is greater than the secretory activity, whence the consistency of the contents, which at the commencement of the large intestine are still semi-liquid, but become more consistent in the further course of the intestine. The absorption includes not only the water and the products of digestion in solution, but also, under certain circum- stances, even unchanged fluid proteids. Also toxic substances are de- cidedly more readily absorbed here than from the stomach. The feces begin to be formed only in the lower portion of the large intestine. The cecum in some animals, as, for example, the rabbit, is of considerable size ; fermentative decompositions appear to take place in it with great activity, with the development of an acid reaction. In human beings the cecum is principally an organ of absorption, as the abundance of lymphatic follicles indicates. From the lower portion of the small in- testine and from the cecum onward, the ingesta acquire the fecal odor. Observations on Thiry's intestinal fistulae permit the conclusion that a considerable portion of the feces is derived from the secretion of the mucous membrane and from epithelial desquamation. The amount of feces evacuated equals, on an average, 170 grams in twenty-four hours (from 60 to 250 grams), although, when large amounts of food, especially if difficult of digestion, are taken, even more than 500 grams may be discharged. After a diet of animal food the amounts of feces and of solid residue therein are less than after a vegetable diet. The consistent feces are broken up by the development of gas, and there- fore float on water. The consistency of the feces depends on the amount of water con- tained in them, which usually reaches 75 per cent. A pure meat- diet causes rather dry feces; food rich in sugar, rather watery feces; while the amount of fluid ingested is without influence. The more 336 PROCESSES IN THE LARGE INTESTINE. rapidly peristalsis takes place, however, the more watery are the feces, because there is not sufficient time for the absorption of fluid from the rapidly advancing ingesta. Paralysis of the intestinal blood-vessels and lymph- vessels, after transection of the nerves, is likewise accompanied by liquefaction of the feces. The reaction of the feces is often acid, particularly in consequence of lactic-acid fermentation of large amounts of carbohydrates ingested. Numerous other acids generated by fermentation are also present. If, however, considerable amounts of ammonia are produced in the lower portion of the intestine, a neutral and even an alkaline reaction may preponderate. The secretion of large amounts of mucus in the intestine favors a neutral reaction. E. St. G. SI. Mm B. Lm. FIG. 124. Longitudinal Section through the Large Intestine: E, epithelium; St, mucous membrane; G, blood- capillaries; SI, solitary follicles; C, circular muscular layer; Ms, muscular layers; Lm, longitudinal muscular layer; Ld, Lieberkiihn's glands; Mm, muscularis mucosEe; B, connective tissue. The odor of the feces, which is more pronounced with a meat-diet than with a vegetable diet, is dependent upon the fecal-smelling products of putrefaction not yet prepared in an isolated state ; further upon the volatile fatty acids, as well as upon traces of methylmercaptan. The last-named substance can be prepared from proteid by means of fused potassium hydroxid, and it develops in traces on boiling varieties of cabbage, and it is also formed from hydrogen sulphid (as from eggs). The color of the feces varies in accordance with the amount of altered biliary pigment present, hence shades vary from light yellow to dark brown. PROCESSES OF THE LARGE INTESTINE. 337 In addition, the color of the food has considerable effect. Thus the presence of much blood in the food renders the feces almost brownish black, from hematin; green vegetables render them brownish green, from chlorophyll; bones, in dogs, render the feces white, from the calcium contained; bluish-red vegetable juices render them bluish black; iron-preparations stain them black in part, from the production of iron sulphid. The feces contain (Fig. 125): i. The secreted juice of the intestinal mucous membrane, together with desquamated and digested epithelial cells. After almost complete absorption of the digested food, the feces still contain from 8 to 9 per cent, of nitrogen, from 12 to 18 per cent, of ethereal extract and from ii to 15 per cent, of ash. Certain articles of food stimulate these excre- tions more vigorously than others. If a loop of the lower portion of the small intestine and the upper portion of the large intestine be excluded, as in a Thiry's fistula, and it be replaced in the FIG 125. Feces: a, muscle fibers; b, tendon; c, epithelial cells; d, leukocytes; e-i, various forms of plant-cells, among which everywhere large numbers of bacteria (i) are scattered; between h and b are yeast-cells; *, ammoniomagnesium phosphate. abdominal cavity after being closed by a circular suture, a mass of fecal char- acter will be found in it. A loop of colon, thus excluded, will contain only a watery transudate, rich in salts. 2. The indigestible residue of the tissues of animal or vegetable food: hairs, horny tissue, elastic tissue; most forms of cellulose, wood-fibers, fruit-stones, spiral vessels from plant-cells, gum. 3. Fragments of otherwise readily digestible substances, particularly when they were ingested in excessive amount, or when not sufficiently comminuted by mastication; thus, the remains of meat (up to i per cent.), pieces of ham, shreds of tendon, bits of cartilage, flakes of fatty tissue, small pieces of hard albumin; further, plant-cells, starch in vegetable cells, firm-walled cells of ripe pulses, unground adhesive cell of grain, and the like. The presence of meat and starch is suggestive of an existing intestinal catarrh. Of all articles of food certain remnants pass over into the feces: of wheat- bread, 3-7 Per cent.; of rice, 4-1 per cent.; of meat, 4.7 P^ cent.; of potc es, 9.4 per cent.; of cabbage, 14.9 per cent.; of rye-bread, 15 per cent.; of carrots, 20.7 per cent. 338 PROCESSES OF THE LARGE INTESTINE. 4. The metabolic products of the biliary coloring-matter, which are especially abundant in all diseases that cause increased destruction of erythrocytes, and which now no longer yield the Gmelin-Heintz reaction, as well as the altered biliary acids. In diarrhea! stools, as, for example, the green stools, the reaction, however, can often be readily demonstrated. It indicates accelerated peristalsis. The meconium contains unaltered bilirubin, biliverdin, glycocholic and taurocholic acids. 5. Unaltered mucin and nuclein and, as a metabolic product of the latter, xanthin-bases ; nuclein especially after a diet of bread ; in addition, cylindrical epithelial cells from the alimentary tract in various stages of digestion; further, fat-globules at times. Crystals of cholesterin and of coprosterin are rare. The less intimately the mucus is admixed with the feces, the lower down in the intestine is its source. 6. After the ingestion of a large amount of milk, as well as after a diet of fat, crystalline needles of calcium-salts of the fatty acids, thus calcium-soaps, are found constantly in the feces, even in infants. When courses of treatment with milk have been pursued undigested masses of casein and fat have besides been observed to be present. Further, com- binations of ammonia with the acids resulting from putrefaction already mentioned are among the substances constantly present in the feces. Larger masses of fat in the feces indicate accelerated peristalsis. 7. Among the inorganic residue, the readily soluble salts, which therefore are readily diffused, are rare in the feces; thus sodium chlorid and other alkaline chlorids, the phosphoric as well as the sulphuric com- binations. On the other hand, the insoluble combinations, principally ammoniomagnesium phosphate, neutral calcium phosphate, yellow- colored calcium-salts, calcium carbonate and magnesium phosphate, constitute 70 per cent, of the ash. The large amount of alkalies and earths contained- in the feces is noteworthy, three-quarters of which are in combination with carbon dioxid and organic acids. These are derived only in smallest part from the secretions of the intestinal mucous mem- brane. By far the greatest part of the ash, however, is derived from the constituents of the food. According to Rey, from 20 to 50 per cent, of solutions of calcium-salts, injected into the blood or subcutaneously, is excreted by the glands of the large intestine in the dog; 0.2 gram of iron is present daily. In the presence of a fistula in the large intestine, Robert and Koch observed, in the feces: sodium, calcium, magnesium, iron; phosphoric, sulphuric, hydro- chloric acids; soaps, neutral fat, fatty acids, mucin, albumin, epithelium, traces of ethereal sulphates, together almost one gram daily. At times the excretion of inorganic substances is so abundant as to form incrustations upon other fecal matter. Under such circumstances either ammoniomagnesium phosphate is present alone, in large crystals, or magnesium phosphate is mixed with it. Par- ticularly the ingestion of rye-bran, in bread, which contains these substances in large amount, causes this result. Charcot's crystals are found in the presence of entozoa. 8. Bacteria are present in abundance; yeasts are seldom absent. For the identification of the individual bacteria, Escherich has developed pure cultures from the intestinal contents of infants, Bienstock from those of adults. In the intestine of infants, fed upon mother's milk exclusively, the bacterium lactis aerogenes (Fig. 126,2) produces, particularly in the upper portion, where milk-sugar is still unabsorbed, acetic acid, together with carbon dioxid, hydrogen and marsh-gas. Lactates are transformed into butyrates. The bacterium also produces acetic acid from starch. A characteristic feature of the MORBID ALTERATIONS IN DIGESTIVE ACTIVITY. 339 feces is the slender bacterium coli commune (Fig. 126, i), provided with from one to three flagella, which forms lactic and formic acids, together with acetic acid, and at times exerts a pathogenic action. In the feces of adults Bienstock found first of all two varieties of large bacilli pig. 126 3, 4) resembling the bacillus subtilis in size and appearance, differing from the latter only in the form of its pure culture, by its manner of sporulation and by an absence of independent movement. These two bacilli are distinguish- able macroscopically only by the form of this culture, which takes the shape A ^ 2 a ra P e > or of a mesentery. Neither possesses any fermentative activity A third, micrococcus-hke, small, slowly multiplying bacillus (bacillus coprogenus parvus) was present in three-quarters of all of the stools. The fourth variety is the specific bacterium of proteid decomposition (bacillus putrificus coli) which is wanting in the feces of infants, and which with the production a fecal odor gives rise to the putrefactive products of proteids. Only this and no other causes these processes in the intestine; yet it does not decompose casein and alkali- % 3 < / FIG. 126. i, Bacterium coli commune-, 2, Bacterium lactis aerogenes; 3, 4, the two large Bienstock bacilli with partial endogenous spore-formation; 5, the various stages of development of the bacillus of proteid outre- faction. albuminate. The evolution of this bacterium is represented in Fig. 126, 5, a-g; of which the stages c and g are, however, wanting in the feces and are encoun- tered only in artificial cultures. If the feces are simply examined microscopically, without special precautions, the following are found as normal saprophytes: the bacterium coli commune, the staphylococcus aureus; frequently, also, varieties of proteus, at times with infective properties; in addition, other bacteria, whose entrance in part through the anus is possible: the bacillus butyricus, often staining blue with iodin, in feces rich in starch, and other small, spherical and rod-shaped schizomycetes, staining similarly. After the ingestion of uncooked food of various kinds, Lembke was able to verify the presence of as many as 73 different bacteria in the intestine. In human beings, with accidentally acquired intestinal fistulas or an artificial anus (intestinal fistula involving the colon), opportunity is afforded to study the changes in the intestinal contents with greater precision. MORBID ALTERATIONS IN DIGESTIVE ACTIVITY. The ingestion of food may be prevented by spasm of the muscles of mas- tication (usually as a symptom of general convulsions), by strictures of the esophagus, either from corrosive cicatrices (after the swallowing of caustic fluids) or from neoplasms, especially carcinoma. Inflammatory affections of any kind in the mouth and pharynx may also seriously interfere with the ingestion of food. Inability to swallow occurs as a symptom of disease of the medulla oblongata, in consequence of paralysis of the center for the motor nerves (facial, pneumogastric and hypoglossal) and of that for the sensory nerves through which pass reflex impulses (glossopharyngeal, pneumogastric and trigeminal). Irritation or ab- normally heightened stimulation of this area may cause spasmodic swallowing and a feeling of constriction in the throat (globu's hystericus). The secretion of saliva is diminished in conjunction with inflammation of the salivary glands, occlusion of their ducts by concretions (salivary calculi) , etc.; further, under the influence of atropin and daturin, in consequence of which the secretory (not the vasomotor) fibers of the chorda tympani appear to become paralyzed. Slight fever may increase the amount of saliva, though the amount of ferment may be lessened; fever of more marked degree diminishes both, while 340 MORBID ALTERATIONS IN DIGESTIVE ACTIVITY. in the presence of high fever no saliva at all is secreted. The saliva secreted with lower grades of fever is cloudy, viscous and it usually becomes acid. With increase in fever the inertness of the diastatic action also increases. After the crisis the amount of saliva and the activity of the ferment become subnormal; likewise in the presence of diseases of the kidneys. After chronic illness of long standing the production of ferment frequently diminishes. The secretion of saliva is increased by morbid irritation of the nerves of the mouth, as from in- flammations, ulcers, trigeminal neuralgia, so that enormous quantities may be poured out. Mercury and jaborandi-leaves cause salivation, the former with the simultaneous occurrence of a stomatitis that induces reflex secretion of saliva. Diseases of the stomach also may increase the secretion of saliva, in conjunction with paroxysms of nausea and retching. Viscid, ropy saliva, due to irritation of the sympathetic nerve, is secreted, together with some vascular disturbance, in consequence of active sexual excitement, but also as a result of certain psychical impressions. The reaction of the buccal secretion becomes acid in the presence of catarrhal conditions of the mouth and, further, as a result of the decomposition of accumulated epithelial cells in the mouth during the prevalence of fever, as well as in cases of diabetes mellitus, in consequence of acid fermentation of the sugar contained in the saliva. Diabetic patients therefore suffer frequently from carious teeth. The secretion of the mouth in infants also has a slightly acid reaction unless the greatest cleanliness is observed. Disturbances in the activity of the gastric musculature may appear, as a paralytic phenomenon, with distention of the stomach, and a protracted sojourn of the ingesta. With more marked grades of the disorder decomposition and the production of gas take place. Diminution in muscular activity may give rise to dilatation of the entire stomach. Incompetency of the pylorus represents a special form of gastric paralysis. Derangement of innervation, central or periph- eral in nature, may be the cause; further, actual paralysis of the pyloric sphinc- ter or anesthesia of the mucous membrane of the pylorus, which exerts a reflex effect upon the sphincter muscle; finally, also, interference with the transmission of the reflex within the center. Abnormally increased activity of the gastric musculature will, as gastric diarrhea, hasten the ingesta into the intestine; often vomiting occurs. In nervous individuals so-called peristaltic unrest of the stomach is at times present, in conjunction with dyspeptic disorders. Spasm of the cardiac orifice or paresis of the inhibitory nerves of the cardia also occurs. Rarely, in the presence of stricture of the pylorus, true antiperistalsis of the stomach has been observed. Gastric digestion is delayed by all severe physical and mental exertion and, if this be of more marked degree, digestion may even be inhibited. Also sudden emotional disturbance, as well as reflex influences from other organs (uterine dyspepsia), may have this effect. Probably these factors exert an influence upon the vasomotor nerves of the stomach. Impairment and abolition of the secretion of the gastric juice may, under certain conditions, be purely nervous in nature, as in cases of nervous dyspepsia and gastric neurasthenia. Complete absence of the gastric juice is found in connection with atrophy of the mucous membrane, prin- cipally in cases of pernicious anemia. Also excessive secretion of the gastric juice, continuous flow of the juice, and likewise excessive production of acid may depend upon derangement of nervous activity: nervous gastroxynsis, chiefly observed in women. Excessive production of hydrochloric acid occurs in asso- ciation with round ulcer of the stomach. Inflammatory or catarrhal affections of the stomach, as well as ulcers and neoplasms, disturb normal digestive activity, as does also the excessive ingestion of foods difficult of digestion, of sharp spices in considerably amount, or much alcohol. Griitzner observed in a dog that the mucous membrane secreted con- tinuously under the influence of a chronic gastric catarrh, but the gastric juice was deficient in pepsin, cloudy, viscous, less acid, even alkaline. The introduc- tion of food did not modify the secretion; the stomach, therefore, never actually comes to rest. At the same time the chief cells of the gastric glands are turbid. Accordingly it would seem o: advantage for patients suffering from gastric catarrh to eat frequently, but only a little at a time, and in addition use a 0.4 per cent, hydrochloric-acid solution as a beverage. Small doses of sodium chlorid appear to aid gastric digestion. In the presence of enfeebled digestion, the cause may be deficient formation either of hydrochloric acid or of pepsin. Both substances may therefore be administered as remedial agents. In the presence of enfeebled gastric digestion MORBID ALTERATIONS IN DIGESTIVE ACTIVITY. 341 and motor insufficiency decomposition of the contents of the stomach into lactic, butyric and acetic acids often takes place as a result of the action of lower organ- isms. Small doses of salicylic acid are advisable under such circumstances, together with some hydrochloric acid (notwithstanding possible heart-burn or acid eructation). The administration of pepsin probably is but rarely imperative, as this ferment is only seldom absent even from the diseased gastric mucous membrane. In the presence of marked dilatation and a protracted sojourn, the proteids in the stomach, notwithstanding the hydrochloric acid, undergo putre- faction, which, however, does not as a rule have an injurious effect. In cases of gastric catarrh and cholera, albumin has been observed to appear in the gastric juice. Gastric Digestion in Patients with Fever and Anemia. Beaumont, from obser- vations made upon the man with the gastric fistula examined by him, found that only scanty secretion of gastric juice takes place in the presence of fever. The mucous membrane was deficient in secretion, red and irritable. Dogs, which Manassein had made febrile from septicemia or profoundly anemic by venesection, elaborated a fairly active gastric juice, characterized especially by a deficiency of hydrochloric acid. Hoppe-Seyler examined the gastric juice from a patient with typhoid fever in which disease van de Velde found no free hydrochloric acid (for the parietal cells are destroyed under such conditions) ; as well as in cases of gastric carcinoma also, in which disease there is, as a rule, no excess of free hydrochloric acid and found it absolutely inactive for artificial digestion, even after hydrochloric acid had been added. This investigator properly emphasizes the fact that the diminution in hydrochloric acid after such conditions favors the development of a neutral reaction of the gastric contents, by reason of which, on the one hand, digestion in the stomach can no longer take place; while, on the other hand, abnormal fermentative processes must take place, with the aid of developing micro-organisms and sarcinae ventriculi (?). Uffelmann found that, in patients with fever, the secretion of a peptone- forming gastric juice ceases if the fever sets in violently, if a condition of great weakness develops, or if a high temperature persists for a long time. In any event, also the amount of gastric juice secreted is diminished. In the presence of fever the irritability of the mucous membrane is increased, so that vomiting is readily induced. Also the increased excitability of the vasomotor nerves of patients with fever is evidently detrimental to the secretion of active digestive juices. Gluzinski found an absence of hydrochloric acid in the acute febrile infectious diseases. Beaumont observed that fluids were rapidly absorbed from the stomach of a febrile patient, while, on the other hand, the absorption of pep- tones was diminished, on account of the frequently accompanying gastric catarrh and the disturbed activity of the muscularis mucosas. Many salts disturb gastric digestion, if added in considerable amount, par- ticularly the sulphates. Of the alkaloids, morphin, strychnin, digitalin, narcotin and veratrin likewise have a disturbing influence. A small amount of quinin ac- celerates gastric digestion. As the digestive activity of the stomach can be replaced by the pancreas, it is evident that dogs may continue to live without profound disturbance of nutrition after extirpation " of the stomach. Langenbach observed a similar result in human beings after operation. The secretion of bile undergoes a change in the presence of acute disease, as, for example, fever, in that it becomes scanty and at the same time more watery, and that it is poorer in its specific constituents. Should the liver undergo profound structural changes as a result of the morbid process, the secretion of bile may cease completely. As a result of the decomposition of bile (acid fermentation?) gall-stones form within the gall-bladder or biliary passages. These calculi may be white or brown. The former consist almost entirely of laminated cholesterin-crystnls. They are generally about i cm. in diameter, but they may be the size of a walnut or even larger. The brown gall-stones consist of bilirubin-lime, together with biliverdin, bilicyanin and choletelin, and also calcium carbonate and phosphate, often mixed with iron, manganese, copper and other precipitated heavy metals. All gall-stones, like urinary calculi, possess an organic supporting structure. Some are rather spherical, often studded with mulberry-shaped nodules. Those packed together in the gall-bladder become polished, from mutual attrition in consequence of the contraction of the walls of the gall-bladder. The white gall- stones often contain lime and biliary coloring-matter as a nucleus, together with 342 MORBID ALTERATIONS IN DIGESTIVE ACTIVITY. a nitrogenous residue, probably derived from desquamated epithelium, mucus, salts of biliary acids and some fat. Gall-stones may cause obstruction of the bile-ducts and then give rise to symptoms of cholemia. Smaller stones, impacted in the ducts, may cause intense pain (biliary colic) and, by means of their sharp edges, they may even bring about fatal rupture of the ducts. The formation of biliary calculi is probably due ultimately to local stagnation and decomposition of bile in the gall-bladder, caused, for example, by tight lacing, in consequence of which kinking of the gall-bladder takes place. Cholemia and jaundice have already been discussed. In the presence of high fever the pancreatic secretion appears to be dimin- ished and its activity enfeebled. Cessation of secretion is attended with the appearance of fat in the form of globules and crystalline fatty acids in the feces. Degeneration of the pancreas may cause diabetes. Among the disturbances in the activity of the intestinal tract, constipation (obstipation) is first to be considered. The causes of this condition may reside in: (1) Obstructions that occlude the normal passage. In this category belong constrictions of the intestinal canal, due to cicatricial strictures, as, for example, in the colon often after dysentery; neoplasms; further, axial torsion of a loop of intestine (volvulus), or invagination of one portion into another (intussuscep- tion) , or into a hernial sac (hernia) ; also the pressure of tumors or exudates from without. Finally, congenital absence of the anus may constitute the cause. (2) Excessive dryness of the intestinal contents may cause obstipation. Under such circumstances the following factors may be operative: Excessive dryness of the food; further, diminution of the digestive juices, as, for example, of the bile in cases of icterus ; or in consequence of great loss of fluid through other organs of the body, as after profuse perspiration or secretion of milk, or, finally, during fever. (3) Derangement of the activity of the muscles and of the motor nerve- apparatus of the intestine may induce constipation through insufficient peristal- sis. This is caused especially by paralytic conditions, as in the presence of in- flammation, degeneration, chronic catarrh and peritonitis. Spinal paralysis is generally attended with sluggish defecation; central affections often also. Whether the phenomena of mental impairment and hypochondriasis are the ac- companiment or the sequel of constipation has not yet been demonstrated. Spasmodic contraction of certain portions of the intestine may give rise to transi- tory retention of the intestinal contents, with great pain (colic) ; as may also spasm of the anal sphincter, which may also take place reflexly, from irritation of the lower portion of the intestine. The feces are almost always hard and deficient _in water, when constipation exists, because during their long sojourn in the in- testines fluid is absorbed from them. In consequence, the fecal masses form large pieces (scybala) within the large intestine and these may, in turn, constitute a new obstacle to the onward movement (coprostasis) . Diminution in the intes- tinal and gastric secretion occurs also as a sign of general nervous affections (hys- teria, hypochondria, mental disorders), although increased secretion may also take place under such circumstances. The agents that cause constipation are, in part, those that paralyze the motor apparatus temporarily, such as opium or morphin; and, in part, those that dimin- ish the secretions of the intestinal mucous membrane, and exert a constringent effect upon the blood-vessels and the mucous membrane, such as tannic acid, alum, lime, lead acetate, argentic and bismuth nitrates. Increase in the intestinal discharges is usually accompanied by a greater degree of fluidity of the feces (diarrhea). The causes are as follows: 1. Unduly rapid propulsion of the contents through the intestinal canal, particularly through the large intestine, so that absorption from this part cannot take place in a normal manner. The increased peristalsis is due to irritation of the motor-nerve apparatus of the intestine, and is principally reflex in character, Rapid passage of the ingesta through the intestinal canal results in the presence in the discharges of substances that could not be completely or at all digested in the short time afforded (lientery) . This will also occur if portions of the in- testine, situated high up, communicate with lower portions of the intestine, through abnormal openings. 2 . The feces may be of the consistency of paste from the admixture of water, mucus and fat, in considerable amount; further, from the residue of fruits and vegetables. In rare cases in which the feces contain a good deal of mucus, so- called Charcot's crystals are present (Fig 92, c). In the presence of ulceration of the intestine, leukocytes (pus-cells) are found. COMPARATIVE PHYSIOLOGY OF DIGESTION. 343 3. Diarrhea may develop in consequence of disturbances of the processes of diffusion through the intestinal walls. Affections of the epithelial cells should be mentioned in this connection: swelling in association with catarrhal or in- flammatory conditions of the mucous membrane. As, further, in the process of absorption independent activity on the part of the cylindrical cells is to be taken into consideration, controlled, perhaps, by the nervous system, it is plain how sudden agitation, from fright, anxiety, etc., may cause diarrhea. 4. Diarrhea may be the result of increased secretion. In its simplest form this occurs through capillary transudation, when salts, as, for example, magne- sium sulphate, introduced into the intestine, remove water from the blood by endosmosis. In this category belong the copious watery discharges that take place in consequence of alteration of the intestinal epithelium, as in cases of cholera, in which such excessive transudation takes place into the intestine that the blood becomes inspissated and may even stagnate in the veins. In addition, transudation into the bowel may take place in consequence of paralysis of the yasomotor nerves of the intestine. The diarrhea due to cold appears to belong in this group. Certain substances appear directly to irritate the secretory organs of the intestine or their nerves ; among these are the drastic purgatives. Pilocarpin injected into the blood also induces marked secretion. In the presence of febrile disorders, the secretion of the intestinal glands appears to undergo quantitative and qualitative changes, with simultaneous derangement in the activity of the intestinal musculature and the organs of absorption and increased irritability of the mucous membrane. With respect to fermentations in the intestine, the fact should be emphasized that all, in excess, as, for example, the butyric or the acetic, give rise to patho- logical manifestation. With regard to the pathogenic schizomycetes acting from the intestinal canal (cholera, typhoid, dysentery, and others) reference may be made to p. 246 Flagellated trichomonads are exceedingly rare. Finally, attention should be directed to the fact that, in consequence of abnormal decompositions in the intestinal canal, substances may be formed that exert a toxic effect upon the organism and thus give rise to auto-intoxications. COMPARATIVE PHYSIOLOGY OF DIGESTION. Among mammals, herbivora possess larger salivary glands than carnivora, while omnivora occupy an intermediate position. Whales have no salivary glands at all; the pinnipeds have a small parotid, the echidna none at all. The dog, like some carnivora, has an additional zygomatic gland situated in the orbit. In birds the salivary glands empty at the angle of the mouth; the parotid gland is wanting. Among snakes the parotid glands are in some species transformed into poison-glands; tortoises have sublingual glands; in addition, reptiles have labial glands at the margin of the lips. Amphibia and fish have only small, disseminated buccal glands. In insects the salivary glands are widely distributed, partly unicellular (as, for example, two pairs in lice), partly com- pound; several pairs of them are usually present. In some the secretion contains formic acid, for which reason the stings of these animals cause burning and in- flammation; in others the secretion is strongly alkaline, as that from the large salivary glands of the bed-bug. In bees and ants the lower salivary glands secrete a sort of cement-substance. The web-glands on the lower lip of caterpillars secreting the silky material, principally those of the silk-worm, should not be confounded with the salivary glands. Among vermes, leeches have unicellular salivary glands. In snails the salivary glands are also widely disseminated, and the saliva from dolium galea contains more than 3^ per cent, sulphuric acid, which also is present in murex. cassis, and aplysia. Cephalopods have a double set of salivary glands. In the octopus the saliva digests fibrin, but not starch, and it is poisonous. Crop-like formations are wanting in all mammals; the stomach appears to be single, as in human beings, or divided into halves, as in many rodents, into a cardiac portion and a pyloric portion. The stomach of ruminants consists of four portions: the first and largest is the paunch (rumen), the next the honeycomb-bag (reticulum). In these two portions, principally in the paunch, the ingesta undergo maceration and fermenta- tion. They are now returned to the mouth by the action of the voluntary mus- cular fibers passing to the stomach, again thoroughly masticated, and, by the closure of a special semicircular groove (esophageal groove), the bolus is carried 344 COMPARATIVE PHYSIOLOGY OF DIGESTION. into the third stomach, the manyplies (psalterium) , which is absent in camels,. and thence to the true, fourth stomach, the rennet-stomach (abomasum). In the two first stomachs starch and cellulose are digested, the sugar formed in part passing over into lactic acid. The third stomach performs chiefly mechanical work, while the fourth really digests albumin. In the small intestine proteids and carbohydrates are further digested. The intestine is divided into the small and the large intestine. It is short in carnivora, and considerably longer in herbivora. The cecum, which in her- bivora attains considerable size as the most important organ of digestion, and in some rodents is even multiple, represents in human beings an insignificant, typical remnant, and is wholly absent in carnivora. In birds the esophagus, especially in birds of prey and granivora, often possesses a diverticular appendix, the crop, for the maceration of the food. In the crop of pigeons there occurs, at the breeding-season, the secretion of crop-milk, the product of a special gland r which is also used as food for the young. The stomach consists of the proven- triculus well supplied with glands, and the thick-walled muscle-stomach, which, with the aid of the inner horny plates, effects the crushing especially of grain. In the intestine, at the junction with the short large intestine, there is almost con- stantly present a pair of ceca shaped like a glove-finger. The intestinal mucous membrane exhibits principally longitudinal folds. The alimentary canal of fish is usually simple. The stomach frequently represents only a dilatation. Less commonly the pylorus possesses one, more frequently a large number of divertic- ular appendices, containing a large number of glands (appendices pyloricae, as, for example, in the salmon). The mucous membrane of the usually short intes- tine exhibits longitudinal plication, as a rule, or the so-called spiral valve, as in the sturgeon, resulting from a spiral arrangement. The alimentary canal of fish, from the esophagus to the rectum, possesses peptonizing power. The short rectum is provided, in sharks and rays, with a diverticular appendage (bursa entiana). In amphibia and reptiles the stomach is generally a simple dilatation. The intestine is longer in herbivora than in carnivora. Especially interesting in this connection is the fact that the vegetable-eating frog-larvas acquire a much shorter intestine with the metamorphosis that makes them carnivorous, terrestrial animals. The intestinal mucous membrane of reptiles exhibits numerous plications. The liver is not wanting in any vertebrate, and is especially large in fish. The amphioxus has only a diverticulum indicative of the liver. The gall-bladder is wanting occasionally in all classes, in accord with which is the experimental observation that extirpation of the gall-bladder is unattended with appreciable influence on digestion and absorption. The pan- creas is wanting only in some fish. One opening (in the amphioxus) or two open- ings (in the shark, the ray, the sturgeon, the eel and the salmon) lead from with- out freely into the abdominal cavity; the same conditions prevail also in crocodiles. Among the molluscs, snails and cephalopods only have true organs of mastication. Some herbivorous land-snails have a movable, horny grinding plate situated in the upper pharyngeal wall. Horizontal maxillary plates, with hard edges working one upon the other, are present particularly in carnivorous snails with uncovered gills. A horny grinding plate, placed like a tongue, whose peculiar form serves for the systematic differentiation of various snails, is fre- quently present in others. Cephalopods possess a strong biting apparatus in the form of a large, horny pair of jaws, resembling a parrot's beak in shape. They also have a grinding plate upon a tongue-like prominence, studded with spines. The alimentary canal is divided into esophagus, stomach and intestine, at times provided with diverticula. In many mussels the rectum pierces the heart and the pericardium. In snails the anus is usually in the vicinity of the respiratory organs. The liver is, as a rule, large. The vineyard-snail has a cellulose- splitting ferment in the secretion of the liver. In the cephalopods the ink-bag opens into the rectum or near the anus. Among vertebrates crustaceans have a masticating apparatus transformed from feet; in some, true masticating feet are still present; in parasitic crabs there are also sucking mouth-organs. Among arachnids the mites have sucking mouth- organs; in true spiders, there are, in addition to the sucking mouth-organs, horizontally acting clutching jaws, in part connected with poison-glands. Centi- pedes possess a strong pair of jaws, acting horizontally. Of insects, those provided with masticating mouth-organs possess, between the upper and lower lips, two pairs of jaws, acting horizontally against each other, of which the upper (man- COMPARATIVE PHYSIOLOGY OF DIGESTION. 345 dibulae) exceed the lower (maxillae) in strength. In sucking-insects the four jaws are transformed into a long tube with a longitudinal slit (the stinging pro- boscis of the bed-bug), which lies in the semicircularly grooved lower lip as in a case. The proboscis of the butterfly consists of the greatly prolonged lower jaws, lying side by side, and capable of being rolled up, while the development of the upper jaws has been arrested. Bees have a sucking tongue, which lies in a groove formed in the lower jaws; in addition, the feeble upper jaws still per- sist as organs of mastication. In crustaceans the esophagus is short; in some the stomach is a simple dila- tation, in others it possesses diverticula, in which are situated the bile-producing glands. The fresh- water crab and its relatives possess a strong chitinized in- tima in the stomach, which is capable of acting as a masticating organ. This membrane is expelled when the skin is shed. Among arachnids, scorpions have a simple alimentary canal. True spiders possess a narrow esophagus and a circular stomach; in addition diverticula on all sides, at the base of which liver- tissue is present, and which may extend even down into the feet. In insects, in addition to the esophagus and the chyle-stomach, generally rich in glands, and at times serrated, there are present various portions, such as the crop in the cricket for instance, the sucking stomach in the butterfly, the masticating stomach in the beetle, in varying manner. The intestinal canal is usually shorter in carnivorous than in herbivorous insects. In the intestine of the flour- worm (tenebrio) ferments are present resembling those of the pancreatic juice. It is remarkable that, in the larval state, as, for example, of most bees, the tract is closed below the chyle-stomach. The rectum, with its auxiliary apparatus, exists by itself and empties, as an excretory duct, into the anus. Peculiar long, tubular excretory organs, the Malpighian vessels, several of which are present, open at the junction of the small and the large intestine. Of the vermes, tape-worms, as well as the acanthocephala (echinorhynchus) among round worms, have no special digestive organ, but are nourished byendos- mosis, through absorption on the part of the skin. The anus is wanting in trematodes (distomum), thread-worms, and almost all turbellaria. In the first, as well as in leeches (sanguisuga) , the buccal orifice is surrounded by a sucking- cup, which, in leeches, possesses, in its depth, three dentated cutting organs. Some leeches, as well as the planaria, have a protrusile proboscis. The intestine of turbellaria, unprovided with an anus, is shaped simply like a glove-finger. It is variously branched in liver-flukes (distomum) . In the annulate worms the in- testine extends from the anterior to the posterior extremity of the body; both mouth and anus are present. Among them, the earth-worms possess a muscular pharynx, while leeches have a highly distensible stomach, provided with many lateral diverticula, which, when the animal has sucked itself full, can be incised through the skin of the back, so that the blood flows continuously from the wound, while the animal continues to take up blood through its sucking mouth (bdel- lotomy) . All vermes are unprovided with a liver. All echinoderms possess an intestinal canal. The mouth is often provided with a biting mechanism, which appears in sea-urchins in the form of five enamel- teeth connected with a movable, complicated maxillary apparatus (Aristotle's lantern) . Many of the starfish are unprovided with an anus ; a bile-like secretion is found in diverticula of their stomach. Salivary glands have been found in sea-urchins. The aquatic celenterates possess no intestinal tract provided with independent walls. The abdominal cavity is the digestive cavity; mouth and anus are repre- sented by the same central orifice, which often is surrounded by tentacles (med- usae, polyps)! A system of canals, passing through the body (medusa?), and con- nected with the digestive cavity, conveys the nutritive fluid and, at the same time, the oxygen-containing water. It is, therefore, the water- vascular-system, and at the same time the nutritive, respiratory and excretory organ. Among the protozoa, the gregarines are nourished by endosmosis through the skin. Infusoria possess mouth and anus, although their abdominal cavity is bounded only by the protoplasm of their body-substance. Rhizopods surround their food with their body-substance and excrete the indigestible material at another portion of the body. In sponges this process takes place from the in- terior of their numerous canals, which penetrate the colonies of their protoplasmic bodies. Digestive Phenomena in Plants. The observations upon the digestion of proteid on the part of a number of plants are highly remarkable. The sundew 346 HISTORICAL. (drosera) possesses, upon the surface of its leaves, numerous tentacle-like processes, provided with glands. As soon as an insect lights upon the leaf, the former is suddenly seized by the tentacles. The glands discharge a juice of acid reaction and digest the animal with the exception of its insoluble chitinous remains. The juice contains a pepsin-like ferment and formic acid. The secretion, as well as, later, the absorption of the dissolved substances, takes place in conjunction with movement of the protoplasm of the leaf-cells. Venus' fly-trap (dionea) and butter-wort (pinguicula) exhibit similar processes, as well as the cavities of the transformed leaves of the nepenthe. Altogether, about 15 species of .such carnivorous dichotyles are known. The juice escaping from incisions in the green fruit of the papaw-tree (carica papaya) possesses peptonizing properties due to a ferment closely allied to trypsin. The milky sap from the fig-tree is likewise active, exerting a diastatic effect and also coagulating milk at 50 C. Albumin is dissolved also by some fungi (boletus, tuber) , lichens (parmelia) and the sap of taraxacum, lactuca, agave and portulac. Artichokes, yellow or lady's bedstraw and other plants contain rennet-ferment. The sap of aloes and of sugar-cane, as well as dried figs, coagulates milk and has a peptonizing action; as does also ordinary flour-dough on admixture; further, the juice (containing peptone at the same time) from the seed of wheat, barley, poppy, beets and corn, after the addition of organic acids. Potatoes and rice have feeble, flour, grain and corn marked sugar-forming activity. HISTORICAL. Digestion in the Mouth. The vessels of the teeth were known to the Hippo- cratic school. Aristotle ascribed an uninterrupted growth to the teeth. In addition, he directed attention to the fact that those animals that exhibit a devel- opment of horns and antlers, cloven-hoofed animals, possess an imperfect denture (absence of the upper incisor teeth) . It is a remarkable fact that, in human beings with excessive formation of horny substance, in consequence of the presence of superfluous hair, imperfect development of the teeth (absence of the incisors) has also been observed. The muscles of mastication were recognized early. Vidius (died 1567) described the maxillary articulation, with the meniscus. The epiglottis, according to Hippocrates, prevents the entrance of food into the larynx. The ancients considered the saliva only a solvent and a means for moistening the food. In addition, in consequence of a knowledge of the saliva of rabid animals and the parotid secretion of venomous snakes, various poisonous properties were ascribed to the saliva, especially from fasting animals a view that Pasteur again confirmed in part, referring the action to pathogenic bac- teria in the secretions of the mouth. Aretasus (81 A. D.) emphasizes the muscular nature of the tongue. The salivary glands had been discovered in ancient times. Galen (131-203 A. D.) was familiar with Wharton's duct and ^tius (270 A. D.) with the submaxillary and sublingual glands. Regner de Graaf established salivary fistulas in dogs in 1663, by tying tubes in Stenon's duct. Hapel de la Chenaye obtained in 1780 for examination large amounts of saliva from a salivary fistula established in a horse. Spallanzani in 1786 stated that insalivated articles of food are more readily digested than those moistened with water. Hamburger and Siebold investigated the reaction, consistency and specific gravity of the saliva and found mucus, proteid and salts present. Ber- zelius introduced the term ptyalin for the characteristic substance in the saliva, though Leuchs in 1831 first discovered its diastatic fermentative action. Gastric Digestion. The ancients compared digestion to cooking, through which solution is effected. Aristotle supposed that, through this "pepsis" chyle (ichor) first developed from the food, and then reached the heart. He also knew of the rennet-action of the stomach. According to Galen, only dissolved masses pass through the pylorus into the intestine. He described the movement of the stomach and the peristalsis of the intestines. ^Elian recognized the four stomachs of ruminants and gave their names. Vidius (died 1567) observed the numerous small glandular openings in the gastric mucous mem- brane, van Helmont (died 1644) expressly mentions the acid of the stomach. He as well as Sylvius (died 1672) compared the action of the stomach with fermentation, in connection with which, according to Descartes (died 1650) and Willis (died 1675), the action of the acid predominates. Reaumur (1752) recognized that a juice was secreted by the stomach that effects solution and with which, together with Spallanzani (1777), he undertook digestive experi- HISTORICAL. 347 ments outside of the stomach. Carminati (1785) then found that the stomach of carnivora, especially when engaged in digestion, secretes an actively acid juice. Prout discovered in 1824 the hydrochloric acid of the gastric juice and Sprott and Boyd in 1836 found the glands of the gastric mucous membrane, among which Wassmann and Bischoff distinguished the two different kinds. After Beaumont (1825-1833) had made his observations upon a man with a gastric fistula, Bassow (1842) and Blondlot (1843) established the first artificial gastric fistulae in animals. Eberle subsequently (1834) prepared artificial gastric juice. Mialhe designated the albumin modified by digestion as albuminose; while Lehmann, who examined this more thoroughly, introduced the name of peptone. Schwann (1836) first prepared pepsin and defined its activity in com- bination with hydrochloric acid. Pancreas, Bile, Intestinal Digestion. The pancreas was known to the Hip- pocratic school. Moritz Hofmann demonstrated in 1641 its excretory duct in the turkey to Wirsung, who (1642) described it in human beings as his dis- covery. Regner de Graaf collected in 1663 pancreatic juice from fistulae, and which Tiedemann and Gmelin found to be alkaline, while Leuret and Lassaigne found it to resemble saliva. Bouchardat and Sandras in 1845 discovered its diastatic, Eberle in 1834 its emulsifying, Purkinje and Pappenheim in 1836 its peptic, and Cl. Bernard in 1846 its fat-splitting properties, to the last of which Purkinje and Pappenheim had already directed attention. Aristotle designates the bile as a useless excrementitious product. Ac- cording to Erasistratus the bile is conveyed from the liver to the gall-bladder through most minute, invisible ducts. Aretaeus attributed the cause of icterus to occlusion of the bile-ducts. Benedetti in 1493 described gall-stones. According to Jasolinus (1573) the gall-bladder is emptied by its own contraction. Sylvius de le Boe (1640) observed the hepatic lymph- vessels, Walaeus (1641) the connective tissue of the so-called capsule of Glisson. Albr. v. Haller pointed out the utility of the bile in the digestion of fat. Henle, Purkinje and Dutrochet (1838) de- scribed the liver-cells. Heynsius discovered urea, Cl. Bernard (1853) sugar, in the liver, and with Hensen (1857), ne found glycogen in the liver. Kiernan (1834) described the blood-vessels more thoroughly. Beale injected the lymph- vessels, Gerlach (1854) the finest biliary passages, Schwann (1844) established the first biliary fistula. Gmelin discovered cholesterin, taurin and the biliary acids. Demarcey pointed out the combination of the biliary acids with sodium (1838). Strecker found the sodium-combinations of both biliary acids and isolated them. Corn. Celsus mentioned nutritive enemata (3-5 A.D.). Laguna (1533) and Rondelet (1554) knew of Bauhin's valve. Fallopia (1561) described the folds and villi of the intestinal mucous membrane, as well as the nerve-plexuses of the mesentery. J. Conrad Brunner (1687) discovered the duodenal glands that bear his name. Severinus (1645) knew of the agminated follicles (Peyer's patches, 1673) and Galeati (1731) knew of Leiberkuhn's (1745) glands in the intestine. PHYSIOLOGY OF ABSORPTION. STRUCTURE OF THE ORGANS OF ABSORPTION. The mucous membrane of the entire intestinal tract, so far as it is lined by a single layer of cylindrical epithelium, that is, from the cardiac orifice to the anus, is capable of absorption. The buccal cavity and the esophagus can take part in this process only to an exceedingly limited extent, on account of their thick, many-layered squamous epithelium. Nevertheless, poisoning, as, for example, with potassium cyanid, may take place by absorption from the mouth alone. The capillary blood- vessels, as well as the chyle- vessels, of the mucous membrane act as the absorbing channels of the intestinal tract. The former convey the materials absorbed almost wholly through the portal vein to the liver, while the latter, uniting in their further course with lymph- vessels, dis- charge the absorbed chyle or milky juice through the thoracic duct into the blood at the junction of the subclavian and internal jugular veins. From the stomach are absorbed aqueous salt-solutions (within six minutes), sugar (namely, grape-sugar, milk-sugar, cane-sugar and mal- tose) in aqueous solution in moderate amount, in alcoholic solution in somewhat larger amount; dextrin and peptone, chiefly in concentrated solutions, in lesser amount; and poisons, especially when dissolved in alcohol. Klemperer and Scheurlen observed that, in the dog, neither fat nor the fatty acids were absorbed. The empty stomach absorbs more rapidly than that filled with food. Diseases of the stomach and fever cause delayed absorption. In addition to absorption, an active secretion of water into the stomach, takes place, in general, in greater degree in proportion as the amount of absorbed substances is greater. The small intestine constitutes the principal field of absorption, pre- senting, especially in its upper half, through its many folds of mucous membrane and through the innumerable cone-shaped villi projecting from them, an extraordinary expanse of surface for absorption. The villi are close together at their bases, so that the entire surface of the mucous membrane appears to be covered with them. In the spaces between their bases the numerous simple tubules of Lieberkiihn's glands empty. Each villus is to be regarded as a projection of the entire mucous mem- brane, for it contains all of the elements comprised within it. The cloak-like covering of the villi consists of a single layer of cylin- drical epithelium with intervening isolated mucous goblet-cells. The surface of the cells directed toward the lumen of the intestine is poly- gonal (Fig. 127, D) and, viewed from the side (C), exhibits a broad seam-like outline, which was formerly considered the thickened wall of the cell-membrane and was designated by the term "lid-membrane." This seam exhibits a delicate longitudinal striation, which was inter- preted in part as the expression of the constitution of the lid, of rods 348 STRUCTURE OF THE ORGANS OF ABSORPTION. 349 arranged as a mosaic, in part as pore-canaliculi, intended for the passage of the finest fat-granules. As a matter of fact, however, this seam belongs only to the longitudinal surfaces of the epithelial cells and is comparable to the thickened edge of a cylindrical vessel, open above. The protoplasmic cell-contents, which enclose a large elliptical nu- cleus with nucleolus in the lower portion of the cell, end approximately on a level with this edge, although at the same time, they contain, at the level of the thickness of this marginal seam, many pseudopod-like proto- plasmic processes, which, standing side by side, and arranged in bundles, are surrounded by the edge of the marginal border. Thus, when viewed from the side, the lid-membrane appears striated, while, as a matter FIG. 127. Structure of the Absorption-apparatus of a Villus: A, transverse section of a villus, in part ; a. cylindrical epithelium, with thickened border (b); c, a goblet-cell; i, i, framework of the adenoid tissue of the villus; d, d, cavity within this, in which lie lymphoid cells (e, e); f, central lymph-space in transverse section. B, two cylindrical epithelial cells with extended pseudopod-like processes of the cell-protoplasm, participating in absorption of the fat-granules. C, cylindrical epithelium after absorption of the fat-granules has been com- pleted. D, cylindrical epithelium of the villus, viewed from the surface, with a goblet-cell in the center. of fact, neither the lid nor the mosaic plates or pores attributed to it exist. The cells are, therefore, open toward the intestinal surface. The protoplasmic processes, standing close together, and resembling the cilia of ciliated epithelium, are directed from the interior of the cell toward the periphery of the intestine. In their midst, near the free sur- face, lies a diplosoma.' These protoplasmic processes are rapidly extended from the cell-body beyond the edge of the cell-membrane, and in a manner comparable to the pseudopods of amoebae, they seize the finely granular fat and draw it into the cell-body. Moistening with bile appears especially to promote their activity, as the movement is not observed in villi not moistened with bile. 35 STRUCTURE OF THE ORGANS OF ABSORPTION. In addition, the medulla oblongata, the spinal cord or the dorsal nerves must have been divided for about a day previously. This apparently depends upon the fact that, in the preparation of an uninjured animal (frog), the fresh division of nerves that becomes necessary acts as an irritant, as a result of which the cells settle down to rest, like irritated amoeba? or like the corneal cells after irrita- tion of their nerves. This fact points to an influence of the nerves upon absorp- tion. When the epithelial cells are filled with fat -granules, the processes are withdrawn into the interior of the cell. The border then appears unstriated, and a transparent zone lies between it and the cell-proto- plasm. The goblet-cells appear to be engaged principally in the secre- tion of mucus; although small fat-granules are also occasionally seen within them. Pathological: In cases of cholera, as well as after poisoning with arsenic and muscarin, enormous desquamation of intestinal epithelium takes place. According to the views of Eimer, Heidenhain, v. Than- hoffer and others, the con- stricted root-ends of the epithe- lial cells communicate with anastomosing connective-tissue corpuscles of the villous tissue. Into these the fat-granules are believed to migrate from the interior of the epithelial cells. The soft connective-tissue cells, finally, are thought to com- municate with the central lymph- vessel ; and in this man- ner a communication is estab- lished between the epithelium and the latter. Thus, the fat- granules would migrate through the body of the connective- tissue cells, as through lymph- canaliculi, to the central lymph- vessel. The author is able to agree with this conception with a modification, which approaches the views of His, Briicke and v. Basch. As a result of his investiga- tions he believes that the epithelial cell narrows toward its lower extremity, like a funnel; the cell-membrane entering, in various direc- tions, directly into communication with the supporting cells of the adenoid tissue of the villus, as well as with the subepithelial branching layer of the villus, which, accordingly, must be perforated in many places. The supporting cells of the villous tissue surround a spongy system of cavities within which lie protoplasmic, nucleated stroma-cells (Fig. 127, A) of varying appearance. The latter at times contain fat- granules in suspension. According to v. Davidoff , these cells are formed by constriction from the lower extremities of the epithelial cells, which, in time, develop a nucleus within themselves. These cells, like ameboid cells without capsules, communicate with one A. FIG. 128. Blood-vessels of an Intestinal Villus: Cn, capillaries; A, artery; Cl, cylindrical epithelium; O, surface of the epithelium; V, vein. ABSORPTION OF THE DIGESTED FOOD. 351 another and with the protoplasm of the epithelial cells, and in them, through active movement of the protoplasm, wander the fat-granules, which the cells take up and again give up within the villus. Thus, the epithelial sheath, with the connective-tissue corpuscles of the villus, forms the supporting apparatus ; the contents of the epithelial cells and the numerous stroma-cells are the active propellers of the fat-granules taken up. Through appropriate interstices in the tissues the cavities containing the stroma-cells communicate with the axial lymph-vessel, which is lined by endothelial cells. It is not improbable that leukocytes frequently migrate from the capillary blood-vessels of the villus into the tissue of the villus and, in part containing absorbed fat-granules, pass over into the central lymph-vessel. According to Schafer, Zawary- kin, Wiedersheim, Stohr, Preusse, Heidenhain and others, the ameboid cells probably migrate from the parenchyma of the villi toward the epithelial layer and perhaps even between the epithelial cells, and return toward the axis of the villus, laden with the substances absorbed. A small artery enters every villus and, lying excentrically, passes to the summit of the villus without division, to give off branches from this point. In human beings this division begins at the middle. The ramifications form a dense capillary network, which lies superficially in the parenchyma of the villus, almost directly beneath the epithelial layer, and from which, either at the apex of the villus or further downward, a vein, running backward, is constituted. The villus is provided with unstriated muscular fibers, both deep- seated, their bundles accompanying the central lymph- vessel longitu- dinally, and also superficial, running rather transversely. The connective tissue of the small intestine has two layers, a deeper, composed of thick, interwoven, mainly collagenous fibers (stratum fibrosum), and lying above this a reticular layer intermixed with elastic fibers (stratum granulosum) , entering into the villi also. Nerves enter the villi from Meissner's mucous-membrane plexus, are provided with small, granular ganglion-cells in their course, and end in part in the muscles of the villi and of the arteries, while in part they appear to communicate with the contractile protoplasm of the epithelial cells. Nerve-filaments pass from Meissner's mucous-membrane plexus to the vessels of the submucosa. Meissner's plexus communicates, by numerous fibers, with a nerve-plexus that spreads throughout the entire thickness of the mucous mem- brane, extends into the villi and supplies the muscularis mucosae, the vessels of the mucosa and Lieberkuhn's glands. The epithelial cells of the large intestine possess no seam-like mar- ginal thickening. The serous coat of the alimentary tract is provided with special lymph- vessels, at first distinct from the chyle- vessels. ABSORPTION OF THE DIGESTED FOOD. PHYSICAL FORCES: ENDOSMOSIS, DIFFUSION, FILTRATION. Endosmosis and diffusion take place between two liquids that are capable of admixture, as, for example, hydrochloric acid and water, but never between two fluids that are opposed to admixture, as, for instance, oil and water. If two miscible dissimilar liquids are separated from each other by a membrane provided with physical pores, such as may be present even in apparently homo- geneous membranes, an interchange of the constituent parts takes place through the pores of the membrane, until finally both fluids have the same composition. This process is designated endosmosis or diosmosis. The endosmptic passage of a substance through the membrane takes place if a solvent liquid having an attraction for the substance is present on the other side of the membrane. 352 ABSORPTION OF THE DIGESTED FOOD. If both miscible fluids are simply placed over one another in a vessel, without the intervention of a porous septum, an interchange of particles of the liquids also takes place, until the entire mass has undergone homogeneous admixture. This interchange is designated diffusion. The rapidity of diffusion is influenced: i. By the nature of the fluids. Acids pass over most rapidly, alkaline salts more slowly; liquid albumin, gelatin, gum, dextrin, and starch-solutions most slowly. The latter, in part, do not crystallize, and also in part do not represent true solutions, but only suspensions. 2. The more concentrated the solutions, the greater is the diffusion. 3. Heat promotes, cooling retards, diffusion. 4. If the solution of a body difficult of diffusion is mixed with a readily diffusible solution, the former diffuses with even greater difficulty. 5. Dilute solutions of various substances diffuse into one another without difficulty, while concentrated solutions mutually retard diffusion. 6. Double salts, of which one constituent diffuses more readily, and the other with greater difficulty, may even be separated chemically by diffusion. In the endosmotic interchange of fluids, the passage of the fluid-particles takes place independently of the hydrostatic pressure. Fig. 129 is a simple illustration of endosmotic exchange. A glass cylinder is filled with distilled water (F). A flask (J) is kept immersed in the water to a suitable height, and closed by a membrane (m) replacing its broken bottom. From the neck of the flask, in which it is tightly corked, projects a glass tube (R) . The flask is filled with concen- trated salt-solution up to the level of the lower extremity of the tube. The flask is introduced into the glass cylinder to such a distance that both fluids stand at the same level (x). In a short while the fluid rises in the tube (R), because particles of water pass through the membrane into the concentrated salt-solution in the flask, and independently of the hydrostatic pressure. The fluid rises in the tube as high as the attraction of the water causes it to. The height of the fluid thus indicates the osmotic pressure. Conversely, also, particles of the concentrated salt- solution pass from the flask into the interior of the cylinder, mixing with the water (F) . This interchange of current continues until an entirely uniform mixture is present in the flask and in the cylinder. Under these circumstances the level of the fluid will to the last always have risen higher in the tube (to y). The circumstance that the level of the liquid within the tube can rise so high and be kept at such a height depends upon the fact that the pores of the membrane are too fine to permit of the action of hydrostatic pressure through them. Therefore endosmosis is defined as an interchange of par- ticles of fluid independently of the hydrostatic pressure. Reflection will show that if, in an endosmosis-experi- ment of similar kind, the water in the cylinder is renewed from time to time, the solution in the flask must become progressively more dilute, until, finally, the flask (J) and the cylinder (F) contain only pure water. Endosmotic Equivalent. It has been found that in endomosis-experiments, equal parts by weight of different fluids or soluble substances (which soon coalesce on the moist surface of the membrane within the flask to form concentrated solu- tions, as, for example, sodium chlorid) being present in the flask, a varying amount of distilled water passes through the membrane, so that, finally, if the water in the cylinder is constantly renewed, a variable amount of distilled water will be pre- sent in the flask. In other words, it has been found that a definite part by weight of a soluble substance in the flask has been exchanged by endosmosis for a definite part by weight of distilled water. The figure that indicates how many parts by weight of distilled water pass over in the endosmosis-flask for a definite part by weight of a soluble substance has been designated by Jolly as the endosmotic equivalent. For i gram of alcohol, 4.2 grams of water are exchanged; for i gram of sodium chlorid, 4.3 grams of water. The endosmotic equivalents for the following substances are: FIG. 129. Apparatus for Diosmosis. ABSORPTION OP THE DIGESTED FOOD. 353 Acid potassium sulphate = 2.3 Magnesium sulphate .. . = n 7 Sodium chlond = 4 . 3 Potassium sulphate = 12.0 Sugar = 7.1 Sulphuric acid = T.Q Sodium sulphate = n.6 Potassium hydrate = 215.0 The amount of the substance passing through the membrane into the water of the cylinder within an equal time is proportional to the degree of concentra- tion of the solution. If, therefore, the water within the cylinder is frequently renewed, the course of the endosmotic equalization is the more rapid. Further, the larger the pores of the membrane and the smaller the molecules of the sub- stance in solution, the more quickly endosmosis takes place. It thus results that the rapidity with which endosmosis takes place varies for different substances. Thus the rapidity for sugar, sodium sulphate, sodium chlorid and urea is, as i : i.i : 5 : 9.5. The endosmotic equivalent for each substance, however, is not constant. It is influenced by: i. The temperature, with increase in which, in general, the endosmotic equivalent increases. 2. C. Ludwig and Cloetta have demonstrated that the endosmotic equivalent varies with the degree of concentration of the penetrating solutions; it is larger for dilute solutions of substances. Should a solution of another substance be present in the cylinder instead of water, an endosmotic current takes place from both sides, until complete equaliza- tion is effected. In this process it is seen that these counter-currents of concen- trated solutions have a disturbing influence on each other. If, however, two sub- stances in, solution are present in the flask at the same time, both diffuse toward the water, without interfering with each other. 3. The endosmotic equivalent varies with the employment of different membranes of different porosity. Sodium chlorid, which has an endosmotic equivalent of 4.3 when pig's bladder is used, possesses an equivalent of 6.4 when a cow's bladder is employed; 2.9 with a swimming-bladder, and 20.2 with a collodion membrane. There are a number of fluids that, on account of the considerable size of their molecules, are capable of passing with difficulty, if at all, through the pores of a membrane impregnated with gelatinous substances, diffusible with difficulty. These consist in part of fluids that contain substances, not in true solution, but in a greatly diluted state of imbibition. Among such substances are the liquid albuminates, solutions of starch, dextrin, gum, mucus and gelatin. They are capable of gradually passing over into and mixing with other fluids by diffusion, in the absence of an intervening porous membrane-wall ; they pass by endosmosis with difficulty, if at all, through the pores of membranes impregnated with gelatin. Nevertheless, the nature of the outside liquid must be taken into consideration; egg-albumin, it is true, passes through membranes into salt-solutions, but not into water; the transudate, under such conditions, becomes more concentrated. Graham has designated the substances in question colloids, because in consider- able concentration they become gelatinous. They also possess the property of not crystallizing, as a rule, while crystalline substances, designated crystalloids, are exchanged by endosmosis. The endosmotic apparatus thus constitutes a mechanism for effecting a separation from mixtures of crystalloids and colloids, which by Graham is designated dialysis. If mineral salts are added to the colloid substances, their ability to pass through membranes is increased. That endosmosis takes place within the alimentary canal, through its mucous membrane and the delicate membranes of the capillary blood-vessels and lymphatics, cannot be denied. On the one side of the membrane, within the tract, there are relatively concentrated aque- ous solutions of salts, sugar, soaps, and peptones, all of which possess slight diosmotic power. On the inner side of the vessels is the colloid, albuminous solution of the blood and the lymph, practically incapable of osmosis, and deficient in the matters in solution within the ali- mentary canal, particularly in the state of hunger. The vital proper- ties, however, probably in consequence of the motility of the proto- plasmic structure within the membranes, also appear to exert some influence upon endosmosis. Thus, Reid observed that the exfoliated frog's skin is less permeable than living skin, and the latter, in turn, more so after irritation had been applied. 23 354 ACTIVITY OF THE WALL OF THE ALIMENTARY CANAL. Filtration is the passage of fluid through the coarser intermolecular pores of a membrane dependent upon pressure. The higher the latter and the larger and more numerous the pores, the more rapidly will the nitrate pass through the pores of the membrane. Increase in temperature likewise accelerates nitra- tion. Further, those fluids filter most readily that most rapidly soak into the membrane in question. Therefore, different fluids vary in the readiness with which they pass through different membranes. Further, the greater the con- centration of the solutions, the more slowly, in general, is their passage. The filter has the property of retaining in part matters from the solutions passing through, either substances dissolved in the fluid (particularly colloid substances) , or water (from dilute solutions of potassium nitrate) . In the former case the filtrate is more dilute, in the latter more concentrated, than the fluid was before its passage through the filter. Other substances pass through without material change in concentration. Should the filtrate enter another fluid, the concen- tration of the transudate increases with the pressure under which filtration takes place. Some membranes exhibit a difference according as filtration takes place from their different surfaces; thus the membrana testacea of the egg per- mits of filtration only in the direction from without inward. The mucous mem- brane of the stomach and intestine also exhibits a difference in this respect. It was formerly believed that filtration of substances in solution could take place from within the digestive canal into the vessels: i. If the intestine contracted and thereby exerted pressure directly on the contents. This alone, however, could scarcely have any noteworthy influence, even in case the canal were contracted in two places and the intervening musculature, through contraction, compressed the fluid intestinal contents. 2. Filtration under negative pressure may be effected through the villi, which on contracting forcibly evacuate the contents of the blood-vessels and lymphatics in a centripetal direction. The latter particularly will remain empty, as the chyle in the fine lacteals is prevented from passing backward by numerous valves. When the villi are again relaxed, they will by suction be able to fill themselves with the fluids of the digestive tract capable of filtration. On the other hand, the fact must especially be emphasized that, according to Spee and Heidenhain, the muscles of the villus actively dilate the central lymph- vessels. ABSORPTIVE ACTIVITY OF THE WALL OF THE ALIMENTARY CANAL. The process of digestion prepares from the food in part true solutions, in part finely divided emulsions, whose small globules are surrounded by an albuminoid capsule. Absorption of Solutions. It cannot be denied that true solutions can pass over into the blood and the lymph of the intestinal canal by endosmosis, but some observations indicate that the cellular elements of the digestive tract also participate in the process of absorption through the functional activity of their protoplasm. It has not as yet been possible to refer the forces effective in this connection to simple physical or chemical processes. When Heidenhain introduced methylene-blue in solution into the intestine, he was convinced that the path of its absorp- tion was in part through, in part between, the epithelial cells. The Inorganic Substances: Water, and the dissolved salts necessary for nutrition, are generally easy of absorption, and in large measure by the blood-vessels. In the absorption of salt-solutions by endosmosis, water must naturally pass from the intestinal vessels into the intestine, while the salt-solutions enter the vessels. The amount of water, how- ACTIVITY OF THE WALL OF THE ALIMENTARY CANAL. 355 ever, is but slight on account of the small endosmotic equivalent of the salts to be absorbed. Salts are absorbed in larger amount from con- centrated than from dilute solutions. If, however, considerable amounts of salts with a high endosmotic equivalent are introduced into the in- testine, as, for example, magnesium or sodium sulphate, these salts retain the water for their solution, and in addition more fluid escapes from the vessels of the intestinal wall, and diarrhea results. Conversely, it is evident that, on injecting these substances into the blood, a large amount of water passes from the intestine into the blood, so that con- stipation results, in consequence of the great dryness of the interior of the intestine. It should, however, especially be pointed out that the absorption of solutions of various salts, isotonic with one another, takes place differently. The epithelial cells of the intestine behave like the erythrocytes with respect to the permeability of the solutions. Water is absorbed from the stomach only in small amount. The absorption of fluids takes place best at moderate pressure within the intestinal canal (from 80 to 140 cm. of water-pressure), in connection with which the surface of the mucous membrane is best smoothed out. A greater degree of pressure would compress the intestinal vessels and would accordingly allow absorption to diminish. During digestion, on account of the dilatation of the blood-vessels, absorption takes place rapidly. For this reason warm solutions also are more quickly absorbed from the stomach than cold, the latter causing contraction of the vessels. The fact that a 0.5 per cent, sodium-chlorid solution is better ab- sorbed than water, further a potassium-solution less well than sodium- solutions, and also the extensive absorption of dog's serum in the dog's intestine, are opposed to the view that only physical forces (endosmosis) are concerned in absorption. Some other inorganic substances also, which are not, as such, constituents of the body, are absorbed by endosmosis: potassium iodid, potassium chlorate, potassium bromid; further, iron-salts, as well as dilute sulphuric acid, etc. Carbohydrates in solution have their chief representatives in the different varieties of sugar and principally in dextrose and maltose, which have relatively high endosmotic equivalents, as cane-sugar is gen- erally transformed by a ferment into invert-sugar. Absorption appears to take place relatively slowly, as, at this time, only small amounts of grape-sugar are found in the intestinal vessels and in the portal vein. According to v. Mering, the sugar is absorbed from the intestine by the portal vein. Dextrin is also present in the blood of the portal vein, as boiling with dilute sulphuric acid increases the amount of sugar in this blood. The amount of sugar absorbed depends upon the concen- tration of its solution in the intestine. Therefore, the amount of sugar contained in the blood is increased after a diet rich in sugar, so that it may even pass over into the urine. To this end approximately a 0.6 per cent, solution of sugar in the blood is necessary. Also cane- sugar in small amount has been found in the blood. When a large amount of sugar-solution is present in the intestine, a portion also enters the lymph- vessels. In a girl with a fistula of the receptaculum chyli, not more than J per cent, of the sugar introduced into the alimentary canal was found to be absorbed by the lacteals. The sugar is in part consumed in the blood and in metabolism, perhaps principally in the muscles. 356 ACTIVITY OF THE WALL OF THE ALIMENTARY CANAL. Peptones have an endosmotic equivalent, more than four times smaller than that of dextrose. They can be rapidly absorbed, on account of their ease of diffusion and filtration. Absorption takes place through the blood-vessels, unless excessive amounts are present in the intestine, as after ligation of the thoracic duct, ingested proteids are as well, absorbed as under normal conditions. Peptones have been recovered from the blood, with certainty, in small amounts only. It is, therefore, to be inferred that they are quickly retransformed into true proteids. The mucous membrane possesses the property of retrans- forming peptone into albumin. Heidenhain regards the epithelial cells of the villi as the seat of this transformation. Peptone gains entrance into the blood unchanged only in minimal amount and it disappears from this after its passage through the tissues. If blood containing peptone is kept warm in the presence of a small piece of small intestine, while air is passed through the mixture, the peptone soon disap- pears from the blood. The peptones undoubtedly represent the principal contingent of the albuminates destined for absorption. Of all the proteids they alone suffice to maintain the body equilibrium, as animals fed upon peptone only (in addition to the necessary fat or sugar) are able to maintain their nutrition. They can do the same when fed with propeptone. According to Pfeiffer, the diffusion of the peptones is promoted by a i per cent, solution of sodium chlorid or sulphate. The absorption of grape-sugar and peptone in the stomach and intestine is increased by the addition of certain sub- stances, as, for example, sodium chorid, pepper, alcohol or ethereal oils. In dogs a peptone-solution (5 cu. cm. of a 20 per cent, solution in 0.6 per cent, sodium- chlorid for an animal weighing 8 kilograms) introduced into the blood, causes death. Unchanged Proteids. In spite of their slight power of filtration and (on account of their great endosmotic equivalent) of diffusion, it has been demonstrated with certainty that unchanged proteids, such as liquid casein and the proteids of milk, meat-juice, dissolved myosin, alkali- albuminate, egg- albumin mixed with sodium chlorid, syntonin, gelatin, can be absorbed; their absorption takes place, in part, even from the mucous membrane of the large intestine. The amount of absorbed unaltered albumin is, however, smaller than that of the peptones. Egg- albumin without sodium chlorid, serum-albumin, hemoglobin and fibrin are not absorbed. Many years ago the author made the observation in a young man that after the ingestion of the white of between 14 and 20 raw eggs, with sodium chlorid, albumin was excreted in the urine after from 4 to 10 hours. The amount of albumin thus excreted increased up to the third day, then becoming less and ceasing on the fifth day. The more albumin ingested, the earlier the albuminuria appeared and the longer it lasted. In this case the condition was evidently one in which considerable absorption of unchanged egg-albumin took place into the circulation. If egg-albumin be injected directly into the blood- stream of animals, it likewise passes, in part, into the urine. The soluble soaps form only a part of the fats absorbed, the largest portion of the fat being taken up in the form of a finely granular emulsion. Absorbed soaps have, on the one hand, been found in the chyle; on the other hand, from the circumstance that the blood of the portal vein is richer in soaps at the time of absorption than during the state of hunger, it has been inferred that absorption of the soaps takes place, to some extent, through the intestinal capillaries. Nevertheless, only a small portion of the soaps enters the blood. ACTIVITY OF THE WALL OF THE ALIMENTARY CANAL. 357 The experiments of Lenz, Bidder and Schmidt render it probable that the organism can take up only a limited amount of fat within a certain time, and this may, perhaps, bear a definite relation to the quantity of bile and pancreatic juice. Beyond that amount no more fat is absorbed. Thus, in cats, 0.6 gram of fat an hour was found to be the greatest amount absorbed for every kilogram of body weight. I. Munk and Rosenstein found the absorption of fat greatest from 5 to 8 hours after ingestion, and earlier or later accordingly as the fat was more or less readily liquefiable. The greater part of the soaps in the intestine, transformed into neutral fat, passes over into the chyle. It seems as if the soaps are capable of uniting with glycerin in the parenchyma of the villus to form neutral fat. Perewoznikoff and Will found neutral fat after the injection of both of these ingredients into the intestinal canal, and also C. A. Ewald observed fat to form when he brought soap and glycerin in contact with the fresh, living intestinal mucous membrane. Blood and chyle contain no free fatty acids. In the blood the fat is subsequently decom- posed in the presence of oxygen. Of other organic matters in solution that are introduced into the intestinal tract, some are absorbed, as, for example, alcohol, and many others. Other bodies may be in part absorbed, in part fermented: tartaric acid, citric acid, malic acid, lactic acid, glycerin and inulin ; gum and vegetable mucin, which give rise to the formation of glycogen in the liver; and it is probable that unknown products of metabolism are also absorbed. Of pigments, alizarin, alkanna and indigo-carmine are absorbed; others are in part absorbed, such as hematin; chlorophyll is not absorbed. Metallic salts appear, in part, to be held in solution by an excess of albuminates, and to be absorbed at the same time with these (iron sulphate has been found in the chyle) , and, in part, to be conveyed to the liver through the blood of the portal vein. Numerous poisons undergo rapid absorption, prussic acid in the course of a few seconds; potassium cyanid has been found in the chyle. Moreover, the purely physical conception of the absorption even of true solutions by endosmosis and filtration alone is not sufficient. Here, also, the protoplasm of the cells takes at least an active part, for only in this way is it possible to explain how even a slight derangement in the activity of these cells, as, for example, after cold or excitement, may be followed by sudden serious disturbances of absorption, even the escape of fluid into the intestine. Only in this way, also, can the fact be explained that the presence of different spices, in small amount, actively increases absorption in the stomach. If, further, absorption took place solely and alone by endosmosis, water would pass over into the intestine after the injection of alcohol; but this never occurs. Further, salt is absorbed in the intestine from a solution that has less osmotic energy than blood-plasma. Moreover, Brieger observed, after the injection of from 0.5 to i per cent, solutions of metallic salts into ligated loops of the intestine, that transudation of water into the bowel failed to take place; although this occurred when injections of 20 per cent, solutions were made. Absorption of the Smallest Granules. The largest amount of the neutral fats and at the same time also of the fatty acids is absorbed in the form of a milky emulsion prepared by the bile and by the pancreatic juice and composed of minute granules. The individual fat-granules appear to be surrounded by a delicate albuminous membrane, the hap- togenic membrane, which is derived in part from the pancreatic juice. In the absorption of fat-emulsions, the villi of the small intestine par- ticipate primarily and in greatest degree; but the epithelial cells of the 358 ACTIVITY OF THE WALL OF THE ALIMENTARY CANAL. stomach also, as well as those of the large intestine, take part in this process. In the villi the fat-granules are seen: (i) Within the epithe- lial cells, the protoplasm of which is dotted with them. The nucleus remains free from them, yet it is so beset by the innumerable fat-granules as to escape observation. (2) Within the tissue of the villus itself, the granules traverse in large numbers the intercommunicating course of the spaces in the reticular tissue. Not rarely, when absorbed in smaller amount, the granules arrange themselves in connected reticular paths. At times they appear to be collected in undivided, band-like lines; at other times, the entire parenchyma of the villus is completely filled with innumerable granules. (3) At a later period the central lymph- vessel in the axis of the villus appears filled with fat-granules. The amount of fat in the chyle varies in the dog, after generous feeding of fat, from 8 to 10 per cent. The fat disappears from the blood within thirty hours. If chyle, rich in fat, is mixed with blood (even if lake-colored), and is agitated with air, the amount of fat in the mixture diminishes as a result of the action of a lipolytic substance present in the blood, in consequence of which a body, insoluble in ether, is formed. The fat-granules are taken up out of the blood by the various tissues, particu- larly by the liver, and in smallest measure by the muscles. The consumption of fat in the tissues begins with a division into glycerin and fatty acids, which is followed by the final combustion. With regard to the forces that effect absorption of the fat-gran- ules, it appeared conceivable from observations made by v. Wisting- hausen that moistening of the porous membranes with bile is capable of facilitating the passage of fat-granules ; but this does not adequately explain the abundant and rapid absorption. It appears most probable that the protoplasm of the epithelial cells of the alimentary tract seizes the fat-granules by an independent movement, and then actively draws them within itself. The protrusion of delicate protoplasmic filaments from the cell-body would take place in a manner similar to that in which the absorption and the inclusion of granular articles of food takes place in the lower organisms, the amoebae. Absorption is possible on the part of the goblet-cells also, because the entrance to the cell remains open. The protoplasm of the epithelial cells communicates directly with the protoplasmic lymphoid cells present in large number within the reticulum of the villus. Thus, the granules may be conveyed to these cells and finally from them, through the stomata between the endothelial cells, into the central lymph- vessel of the villus. The process of the absorption of granules and perhaps the same is in part true of proteids is thus established as a wholly active, vital one. This view receives adequate support from the investigations of Briicke and of v. Thanhoffer and others, as well as the observation of Griinhagen that the absorption of fat-granules in frogs takes place most rapidly at a temperature at which the motile phenomena of the protoplasm are most active. In fact, the conception of a simple physical filtration of the granules into the tissue of the villus is scarcely any longer permissible. This is to be concluded also from the fact that the number of fat-granules present in the chyle is independent of the amount of water present in it. If absorption took place essentially through filtration, the constancy of a direct relation between the amount of fat and the amount of water INFLUENCE OF THE NERVOUS SYSTEM. 359 present would at least be highly probable. The fatty acids, in their passage through the intestinal wall, are retransformed with fixation of glycerin into neutral fats. They pass, in part, through the blood-vessels. The intestine of distomum hepaticum may be considered as a truly classical object-lesson for a study of the cells of the intestine in their functional activity and of the manner in which they accomplish the absorption of solid substances by means of their pseudopod-like processes. Sommer has admirably depicted the conditions, and the author convinced himself of the accuracy of the represen- tation by personal observation of the preparations. Metschnikoff noted similar conditions in celenterates, Du Plessis in turbellaria, Greenwood in earth-worms. If carmine or India-ink is mixed with the food of rabbits, a deposition of either granular pigment takes place in Peyer's patches and in the lymph-cells. Pathological. In the presence of severe intestinal disease, injury to and al- teration in the epithelial cells of the intestine appear to be caused .by a poison elaborated in the bowel, as, for example, in cases of cholera and cholera infantum. INFLUENCE OF THE NERVOUS SYSTEM. Little is known with certainty concerning the influence of the nervous system upon the processes of absorption in the intestinal tract. After division of the mesenteric nerve-filaments, the intestinal contents be- come abundant and watery. This may be due, in part, to deficient absorption, as well as to an increased, paralytic secretion of the intestinal juice, although it is as yet impossible to determine with certainty to what extent transudation into the intestine on the part of the vessels participates in this process. After extirpation of the sympathetic ganglia of the abdomen, symptoms of paralysis of the intestine appear, with exhausting diarrhea, finally terminating fatally; acetone is also present in the urine. Of especial interest is the observation of v. Than- hoffer, who noted the protrusion of filaments from the protoplasm of the epithelial cells of the small intestine only when the medulla oblongata or the dorsal nerves had been divided some time previously. NOURISHMENT BY MEANS OF "NUTRITIVE ENEMATA." In those desperate cases in human beings in which administration of food by the mouth is impossible, c. g., in the presence of stenosis of the esophagus or of persistent vomiting, resort has been had to the procedure adopted by Corn. Celsus, namely, rectal alimentation. As the large intestine is capable of scarcely any digestive activity it is best to introduce fluid material capable of absorption, which is permitted to flow slowly, by its own weight, into the anus, preferably through a long tube provided with a funnel. The recipient must endeavor to retain the material for as long a time as possible. By means of slow and gradual injection, the fluid at times may even pass beyond the ileo-cecal valve. Particles of proteid substances, saturated with a solution of sodium chlorid, may even pass through the small intestine into the stomach, where they may be digested. Nitrogenous substances are to be recommended for this purpose: eggs rubbed up into an emulsion with an aqueous solution of sodium chlorid, peptone or pro- peptone; less well, milk and egg-albumin with sodium chlorid. The commercial preparations of peptone are made by digestion with pepsin, by vegetable ferments or by superheated water, and they often contain much propeptone. An adult should receive daily 120 grams, a child 50 grams of meat-peptone; Leube ad- vises from 50 to 80 grams dissolved in 250 cu. cm. of water. In addition, as a stimulant and as food-sparer, tea with wine may be given. Leube introduces into the rectum a pasty mixture consisting of 150 grams of meat with 50 grams of reddened pancreatic tissue and 100 grams of water, and it is believed that proteids are peptonized and absorbed here. In addition, as much as 50 grams of grape-sugar dissolved so as to make 300 cu. cm., or starch-paste and dilute lake- colored blood may be employed; also fat-emulsions (not more than 10 grams of fat daily) ; mixed with pancreatic paste, as much as 50 grams of fat can be given. 360 SYSTEM OF LACTEAL AND LYMPHATIC VESSELS. Whether thin soap-solutions are advisable, however, has not as yet been deter- mined. This mode of administering nutriment by means of nutrient enemata, must, however, always remain imperfect; at best only one-quarter of the amount of proteids necessary for the maintenance of the metabolic equilibrium is absorbed. SYSTEM OF LACTEAL AND LYMPHATIC VESSELS. Within the tissues of the body, and even in those without special blood-vessels (cornea) or with but a poor supply, there is present a system of vessels conveying fluid, and within which the movement is only centripetal. These vessels begin within the parenchyma of the organs in widely different ways, and unite in their course to form delicate, then thicker tubes, which empty into two trunks of considerable size at the junction of the common jugular and subclavian veins: the tho- racic duct on the left side, the lymphatic trunk on the right. The importance of the lymph and of its movement in the various organs is apparent in different ways at different points, (i) In some tissues the lymphatics represent the nutrient channels through which the nutrient fluid given off by adjacent blood-vessels is distributed, as in the cornea particularly and often within the connective tissues. (2) In some tissues, as in the glands, for example the salivary glands and the testicles, the lymph-spaces constitute the chief reservoirs for fluid, from which, at the time of secretion, the cellular elements derive their necessary fluid. (3) In addition, the lymphatic vessels everywhere have the task of collecting the fluid with which the tissues are saturated and of conveying it back again to the blood. If the network of capillary blood-vessels be regarded, from this standpoint, as an irrigation-system, which supplies the tissues with nutrient fluid, the lymphatic system can be considered as a drainage-mechanism, which, in turn, conducts away the excess of the transuded fluids. Metabolic products from the tissues, the products of retrogressive metamorphosis, are added to this return- current. The lymph-channels are thus, at the same time, absorbent vessels: substances that would otherwise be carried to the parenchyma of the tissues are thus also absorbed by the lymphatic system. A consideration of these circumstances shows that the system of the lymph-channels represents in reality an appendix to the blood- vascular system ; therefore, further, the lymphatic system cannot be active at all if the circulation of blood is totally interrupted; it operates only as a part of the whole and with the whole. If the lacteals are contrasted with the true lymph- vessels, this is done chiefly for anatomical reasons, because the important and con- siderable paths of the former, which are derived from the entire intes- tinal tract, have especially attracted the attention of investigators since antiquity and are to a certain extent an almost independent division of the lymphatic system, with conspicuous absorptive activity. In addi- tion their contents, of white color from the generous admixture of fat- granules, as chyle or lacteal fluid, appeared at first sight to be essen- tially distinct from the clear and watery fluid of the true lymphatics. From the physiological standpoint, however, the lacteals cannot be given an independent position. They are, functionally and structurally, lym- phatics, and their contents are true lymph, mixed with a large amount of absorbed materials. ORIGIN OF THE LYMPH-CHANNELS. LYMPHATICS. 361 ORIGIN OF THE LYMPH-CHANNELS. LYMPHATICS. Development by Means of Secretory Spaces. Within the supporting sub- stances (connective tissue, bone) numerous star-shaped or polymorphous spaces are found that are connected with one another by means of delicate tubular processes. This system of communicating spaces contains the cellular elements of the tissues. The cells, however, by no means completely fill the spaces, an interval often existing between the cell-body and the wall of the space, FIG. 130. Origin of the Lymph-channels: I, from the central tendon of the rabbit (semi-diagrammatic); s, secretory spaces, communicating with the lymphatic at x; a, commencement of the lymphatic fromlthe confluence of secretory spaces. II, perivascular lymphatics. III. lymph-stomata. and varying in size, in accordance with the state of motility of the protoplasmic cells. These spaces are the so-called secretory spaces, or secretory canals, and they represent the commencement of the lymphatics. As adjacent spaces inter- communicate, the propulsion of the lymph is provided for. The eel the secretory spaces are capable of ameboid movement. In part they remain permanently in their spaces (fixed connective-tissue cells, bone-corpuscles); in part they are capable of engaging in active migration through the secretory canal- 362 ORIGIN OF THE LYMPH-CHANNELS. LYMPHATICS. system (wandering-cells). At greater or lesser distances, these secretory clefts are connected with minute tubular lymphatics, which are designated lymph- capillaries (Fig. 130, I, L). Their commencement results from the more intimate approximation of secretory spaces (I, a). The lymph-capillaries, generally exceeding the capillary blood-vessels in caliber, lie principally in the space midway between the arched loops of the blood- capillaries (B). They are composed of delicate nucleated endothelial cells (e), whose characteristic sinuous edges can be stained black by means of a solution of silver nitrate. Between the endothelial cells scattered spaces, stomata, are present. The endothelial cells constituting the wall are often united by bridges of protoplasm. According to Kolossow, the cells may recede from one another at their edges, and thus form spaces between them, while the connecting bands of protoplasm are capable, subsequently, of drawing them together again. Thus, the stomata would develop temporarily and again close. It is to be inferred that the blood-vessel system communicates with the lymph-spaces ; that the blood-plasma finds its way into the lymph- spaces from the thin- walled blood-capillaries through their stomata. In the lymph-spaces this fluid maintains the nutrition of the tissues, inasmuch as the necessary constituents are taken up independently by the tissues. The materials consumed are returned to the lymph- spaces and later reach the lymph-capillaries, which finally deliver them to the venous system. To what extent the cellular elements within the lymph-spaces exert any action upon the discharge of blood-plasma and later upon its propulsion into the lymphatics can only be surmised. It can be conceived that, through con- traction and diminution in size of their cell-bodies, as well as through partial change in position from the group of secretory spaces closer to the blood-vessel to that directed toward the lymph-capillary, they might exert suction upon the blood- plasma transuded. If the cells, themselves, then take up the transuded fluid, the conception is permissible, further, that by subsequent contraction they ex- press this fluid in a certain direction, namely from secretory space to secretory space, toward the lymph-capillaries. In consequence of the independent migra- tion of the cellular elements through the secretory spaces into the larger lymph- paths, small particles that may be contained in the secretory spaces (as, for ex- ample, pigment-granules that have been rubbed into the tissue of the irritated, horny skin in the process of tattooing, and also minute fat-granules, bacteria and the like), and which the lymph-cells are capable of taking up through ameboid movement, may be propelled onward. After what has been said concerning the migration of leukocytes from the blood-stream through the stomata between the endothelial cells of the capillaries, or through the walls of smaller vessels, the migra- tion of cellular elements from the blood-vessel system into the com- mencement of the lymph-channels may be regarded as a normal process. Granular pigments pass from the blood into the protoplasmic bodies of the cells in the lymph-spaces. Only when the granular substance is present in large amount is it distributed into the ramifications of the lymph-spaces as a granular injection. The origin of the lacteals within the villi has been outlined in their descrip- tion as organs of absorption. Commencement of the Lymphatics in the Form of Perivascular Spaces. In the tissue of bony substance, of the central nervous system and of the liver, the smallest blood-vessels are surrounded by wider lymph- vessels, so that the blood-vessels lie in the lymph- vessels like a finger in a glove. In the brain these lymph- vessels are in part constituted of delicate connective-tissue fibrils, which, partly traversing the lumen of the lymph-canal, are supported upon the sur- face of the blood-vessel. Fig. 130 II, B represents in transverse section a small blood-vessel (B), with a peri vascular lymph-vessel, from the brain; p is the tra- versed lumen of the lymph- vessel. In addition to these so-called peri vascular spaces of His, the cerebral vessels are provided also with lymph-spaces within THE LYMPH-GLANDS. 363 the adventitia (Virchow- Robin spaces). In part these possess a well-developed endothelmm. In their further course, where the vessels increase in caliber, the blood-vessel penetrates the wall of the lymph-vessel at one spot, and both continue separately side by side. Wherever the lymph-vessels serve as peri vascular sheaths, the passage of blood-plasma and lymph-cells into the lymph-stream is greatly facilitated. It should be especially mentioned that, in tortoises, even the larger vessels are often covered by the lymph- vessels as a sheath. In Fig. 130, II, A, the bifurcation of the aorta, with the peri vascular lymph- vessels, is shown according to Gegenbaur. The animals referred to exhibit macroscopically the same relations that warm-blooded animals present microscopically; ancl thus the illustration may serve also as the microscopical picture of small peri- vascular lymph- vessels in warm-blooded animals. Commencement in the Form of Interstitial Spaces Within the Viscera. In the testicles the lymphatics commence simply in the form of numerous spaces, which occur between the multifarious coils and convolutions of the seminiferous tubules. They will, therefore, here present the form of spaces bounded by the arched, cylindrical surfaces of the tubules. The limiting surfaces are, however, lined with endothelmm. The lymphatics acquire independent tubular walls only beyond the parenchyma of the testicle. Similar conditions are found in the kidneys. In many other glands the glandular substance is likewise sur- rounded by lymph-spaces. Into these the blood-vessels first pour lymph, from which the secreting cells remove the material for the formation of the glandular secretion, as, for example, the salivary glands. Commencement by Means of Free Stomata upon the Walls of the Larger Serous Cavities (Fig. 130, III). From the investigations of v. Recklinghausen , C. Ludwig, Dybkowsky, Schweigger-Seydel, Dogiel and others, it has been found that the old view of Mascagni, that the serous cavities communicate freely with the lymphatics, is correct. Upon examining serous membranes (most readily the peritoneal lining of the large lymph-cavity in the frog) , best after moistening them with argentic nitrate, followed by exposure to the action of light, disseminated, relatively large, free openings of the stomata are found lying between the endo- thelial cells. Groups of the latter include a stoma among them. A portion of motile protoplasm lies in the cells surrounding the stoma, close to the edge of the opening. Upon the state of contraction of this protoplasm appears to depend the fact whether the stomata are widely open (a) , half closed (b) , or com- pletely closed (c). These stomata are thus the beginnings of the lymph-capil- laries. Fluids, introduced into the serous cavities, therefore readily reach the path of the lymphatics. The cavities of the peritoneum, the pleurae, the peri- cardium, and the serous covering of the testicle, further the arachnoid space, the chambers of the eye, and the -labyrinth of the ear have shown themselves to be true lymphatic cavities; the fluid in them is thus to be designated lymph. Fluids in the peritoneal cavity are absorbed, in part, also by the veins. The endothelial cells of the serous membranes are capable of movement and communicate with one another by means of connecting bridges of protoplasm. In the animal king- dom the free surfaces of the cells are frequently provided with cilia. Even upon the free surface of a number of mucous membranes, it is stated, open pores have been observed as the commencement of the lymphatics: in the bronchi, in the nasal mucous membrane and in the larynx. The larger lymphatics arising from the lymph-capillaries closely resemble veins of equal size in the structure of their walls. Especial stress is to be laid upon the presence of a large number of valves, which are placed so closely behind one another that the distended lymphatic is not unlike a string of pearls. THE LYMPH-GLANDS. The so-called lymph-glands are peculiar to the lymphatic apparatus. They are inappropriately designated glands, because they really represent only many- branched, lacunar, labyrinthine spaces, constituted of adenoid tissue, interposed in the course of the lymphatics. Simple and compound lymph-glands can be distinguished. The simple lymph-glands, more correctly designated simple lymph-follicles or cutaneous follicles, are present either isolated (solitary follicle) , as in the intes- tine, the bronchi, the spleen; or collected in masses (conglobate follicle), as in the tonsil, Peyer's patches, the follicles of the tongue. They are small, spherical vesicles, attaining approximately the size of a pin's head, and they consist through- 364 THE LYMPH-GLANDS. out of delicate elements of the reticular connective tissue intermixed with elastic fibrils and arranged in a network (Fig. 131, C). In the meshes of this network, lymph and lymph-cells are present in abundance. Upon the surface the tissue becomes condensed into a somewhat more independent, conspicuous sheath, which, however, is variously traversed by small spongy spaces in the reticular tissue. Small lymphatics advance everywhere directly up to these lymph-follicles, often keeping considerable areas of their surface covered with a rich network. Fre- quently, also, the surface of the follicle is incorporated into the wall of the vessel, at times throughout a slight, at other times throughout a considerable, extent, so that the surface of the follicle is directly irrigated by the lymph of the vessel ; and, if no direct canal-orifice of considerable size leads from the lumen of the lymphatic into the interior of the spherical follicle, a communication must, never- theless, be assumed to exist between the small lymphatic and the lymph-follicle, and this is adequately provided by the innumerable spaces between the fol- licles. Thus, the lymph-follicle is a true lymphatic structure, whose fluid and lymph-cells can pass over into the stream of the adjacent lymphatics. The follicles are provided, upon their surfaces, with a network of blood-vessels, which also send numerous delicate ramifications and capillaries through the interior of the follicle (A) , within which they are supported by the reticulum (B) . It is to be inferred that leukocytes can pass from these capillaries into the follicle. It should be mentioned as of special importance in connection with these follicles that, in the lymph-glands, the solitary as well as the FIG. 131. A, blood-vessels of the follicle; B, the reticulum and a branch of a blood-vessel; C, lymph-follicle with reticulum and sheath. conglobate glands, an enormous migration of the leukocytes normally takes place uninterruptedly during life through the epithelium be- tween the cells. The leukocytes insinuate themselves between the epithelial cells, but, by their enormous migration, as well as by the divisions that take place during this process, they impair the functions of the epithelium and may even destroy it. Thus, in a measure, physio- logical injuries result, which prepare the way for invading microorgan- isms. The cells that have thus migrated later undergo disintegration. The compound lymph-glands (incorrectly designated lymph-glands) repre- sent to a certain extent an aggregation of lymph-follicles of altered shape. Every lymph-gland is surrounded externally by a connective-tissue capsule traversed by numerous unstriated muscle-fibers, and from whose inner surface numerous septa and bands (Fig. 132, a a) penetrate into the interior of the body of the gland, and divide it into a large number of small compartments. The latter possess within the cortical substance of the gland a rather rounded shape (alveoli), in the medulla, a rather longitudinal sausage-shaped form (medullary spaces) . All, however, are of the same significance and all are connected by communicating orifices. Thus, a rich network of cavities, connected in all directions, is formed within the lymph-gland by the septa. These spaces are traversed by the so- THE LYMPH-GLANDS. 365 called follicular bands (f f). The latter represent to a certain extent the inner- most contents of the spaces, but in such a manner that they are smaller than the spaces and nowhere touch the walls of the cavities themselves. If the cavities of the gland be conceived as injected with a substance that at first has filled them all, but later, by contraction, is reduced to half its size, one will have an approxi- mate picture of the spatial relations of the follicular bands to the cavities of the gland. The follicular bands contain the blood-vessels (b) of the gland within them. About these there is deposited a rather thick cortex of reticular connective tissue, whose meshes (x) are extremely delicate and fine, whose spaces are rich in*lymph-cells and whose surface (o o) is so constituted of the condensed reticulum- cells that a communication between the narrow meshes is still possible. Between the surface of the follicular bands and the inner wall of all the cavities Fio. 132. Part of a Lymph-gland: A, afferent vessel; B, B, lymph-path within the cavity of the gland; a, a, column and septa bounding the cavity of the gland; f, f, follicular band of the cavity; x, x, its reticulum; b, its blood-vessels; o, o, delicate reticular junction between the follicular band and the lymph-pains. of the glands lie the paths of the lymphatics (B B) . Perhaps they are lined by an endothelium; their lumina are traversed by a rather coarse reticulum. The afferent-vessels (A), which spread out upon the surface of the gland, penetrate the external capsule and pass over into the lymph-paths of the glandular cavities (C). The efferent vessels, which exhibit large, almost cavernous anasto- moses and dilatations in the vicinity of the gland, arise at other parts of the gland directly from the lymph-paths. The latter, thus, to a certain degree represent a dense interlacing network of capillary vessels, lying within the glandular cavi- ties, arranged between the afferent and efferent vessels. The movement of the lymph on its way through the many-branched and tortuous lymph-paths of the gland will be retarded and, on account of the resist- ance to the current that the cellular elements, arranged in the paths, must offer, will possess feeble propulsive power. The lymph-corpuscles, lying 11 366 PROPERTIES OF THE CHYLE AND THE LYMPH. of the reticulum, are carried onward by the lymph-stream, so that, after flowing through the glands, the lymph is richer in cells. The lymph-cells lying in the range of the follicular bands may again migrate through the narrow meshes of the reticulum (o) into the lymph-paths, to make good the loss. The formation of the lymph-cells in the follicular bands either takes place locally by division, or new cells migrate from the capillary blood-vessels into the follicular bands. Further on, the muscular activity of the capsule and of the trabeculae should not be underestimated in the movement of the lymph through the glands. Such muscular contraction will express the gland like a sponge. The direction of the fluid thus discharged is governed by the presence of valves within the related lymphatics. Of the chemical substances in the lymph-glands, in addition to those of the lymph, leucin and the xanthin-bodies are worthy of mention. PROPERTIES OF THE CHYLE AND THE LYMPH. Both chyle and lymph are colorless, albuminous, clear fluids, contain- ing lymph-cells. The latter are in reality the same elements that enter the circulation with the lymph-stream, and within the former are desig- nated white blood-corpuscles. The source of the lymph-cells is dis- cussed on p. 370. As, in rare cases, isolated red blood-corpuscles also pass out through the walls of the vessels and into the commencement of the lymph- vessels again, the presence of erythrocytes in the lymph, rarely in the chyle, is readily explained. Red blood-corpuscles can also pass over from the veins into the central extremities of the large lymph- trunks when the pressure in the veins is high. Lymph and chyle con- tain also molecular granules, and fragments of disintegrated leukocytes; chyle contains, in addition, numerous fat-granules. In the lymph a distinction is made between the lymph-plasma and the contained lymph-cells or leukocytes, whose chemical constituents are considered on p. 64. The lymph- plasma contains both of the fibrin- factors, derived from disintegrated lymph-cells. They cause coagulation of the lymph after withdrawal from the body, and in this process the soft, gelatinous, scanty lymph-clot, which forms but slowly, includes the still surviving lymph-cells within it. The fluid remaining, the lymph-serum, contains alkali-albuminates, serum-albumin and some diastatic ferment derived from the blood. Of the coagulable albumi- nates about 37 per cent, consist of paraglobulin. The chyle, which is the sole fluid contained in the lymphatic vessels of the digestive tract (lacteals), can be obtained only in small amounts, before its admixture with the lymph, and it can, therefore, be examined only with great difficulty. A small number of lymph-cells are already present in the first beginnings of the lacteals in the villi; beyond the intestinal wall and, still more, after passing through the mesenteric glands, their number increases. On the other hand, the amount of the solid constitu- ents of the chyle, which is increased after abundant good digestion, is decidedly diminished after the chyle has become mixed with lymph. After the ingestion of food rich in fat the chyle contains many fat-drop- lets (from 2 to 4 /* in diameter), which, however, decrease conspicuously in the further course of the current. The amount of fibrin-factors in the chyle increases with increase in the number of lymph-cells. In addi- tion, chyle contains sugar (up to 2 per cent.), glycogen, peptone adherent to the leukocytes, diastatic ferment absorbed from the intestine, and lactates after ingestion of starches, traces of urea and leucin. PROPERTIES OF THE CHYLE AND THE LYMPH. 367 The chyle from the body of an executed person contained, together with 90.5 per cent, of water: ( fibrin ....... a trace Carl Schmidt found the following inorganic constituents in 1000 parts of chyle from a horse : Sodium chlorid ...... 5-84 Sulphuric acid ..... 0.05 Magnesium phosphate 0.05 Sodium ............ 1.17 Phosphoric acid. . . .0.05 Iron ............. a trace Potassium .......... 0.13 Calcium phosphate. 0.20 The lymph, at the beginnings of the lymphatics, is likewise deficient in cells, and clear and colorless. The fluid from the serous cavities and synovial fluid exhibit similar features. A variation in the lymph, in accordance with the tissues from which it is derived, can with certainty be assumed, although, up to the present time, this has not been estab- lished. After passing through the lymph-glands, the lymph becomes richer in cellular elements and, probably in consequence of this, also richer in solid constituents, particularly proteid and fat. In one cu. cm. of lymph from a dog, 8200 lymph-corpuscles were counted. Hensen and Dahnhardt succeeded in collecting for examination pure lymph in considerable amount from a lymphatic fistula on the thigh of a human being. It had an alkaline reaction and a salty taste. The relative composition of pure lymph, cerebrospinal fluid and pericardial fluid is as follows : Pure Lymph. Cerebrospinal Fluid. Pericardial Fluid. (Hensen and Dahnhardt.) (Hoppe-Seyler.) (v. Gorup-Besanez.) Water ................ 98.63 98.74 95.51 Solids ................. 1.37 1.25 4-48 Fibrin ................. o.n 0.08 Albumin .............. 0.14 0.03 0.06 2.46 Alkali- albuminate ....... 0.09 Extractives ............ 1-26 Urea, leucin ............ 1.05 Salts .................. 0.88 Absorbed carbon dioxid, The cerebrospinal lymph contains a substance to 70 per cent, by volume, that reduces Fehling's solution, and that Naw- of which 50 per cent, could ratzki determined to be dextrose. This, how- be obtained by extraction ever, disappears soon after death. and 20 per 'cent, was ob- tained by addition of acid. 100 parts of lymph-ash contain: Sodium chlorid ____ 74.48 Calcium ........... 0.98 Sulphuric acid ....... 1.28 Sodium ........... 10.36 Magnesia .......... 0.27 Carbon dioxid ........ 8.21 Potassium ......... 3.26 Phosphoric acid ---- 1.09 Iron oxid ............ 0.06 Just as in the case of the blood, potassium and phosphoric acid, of the inorganic constituents, predominate in the cells; while in the lymph-serum, sodium preponderates, principally as sodium chlorid. Only in the cerebrospinal fluid are the potassium-combinations and the phosphates said to predominate. The amount of water in the lymph rises and falls in correspondence with that in the blood. Of gases, dog's lymph contains carbon dioxid in abundance (over 40 per cent, by volume, of which 17 per cent, can be pumped out and 23 per cent, can be removed by acids), traces of oxygen and 1.2 volumes per cent, of nitrogen. 368 QUANTITATIVE RELATIONS OF LYMPH AND CHYLE. QUANTITATIVE RELATIONS OF LYMPH AND CHYLE. It is estimated that the total amount of lymph and chyle introduced into the circulation through the large lymph-trunks in twenty-four hours equals the total volume of the blood. Of this one-half will be contributed by the chyle, the other half by the lymph. The secretion of lymph in the tissues takes place without interruption. From a lymphatic fistula on a woman's thigh, about 6 kilograms of lymph were collected in twenty- four hours. In young horses, the amount of lymph collected from the large lymph-trunk of the neck in from one and one-half to two hours measured between 70 and more than 100 grams. The following influ- ences affect the amount of chyle, as well as that of lymph. The amount of chyle increases considerably during digestion, espe- cially if the quantity of food taken has been large, so that the vessels of the mesentery and the intestine will at this time be constantly found filled with white chyle. In the state of hunger the vessels are collapsed and can be recognized with difficulty. The amount of lymph increases especially with the activity of the organ from which it flows. Thus it was found that active and passive muscular movements increase the amount of lymph considerably, almost five-fold in the horse. Lesser obtained more than 300 cu. cm. of lymph in this manner from fasting dogs, in consequence of which, with inspis- sation of the blood, the animals became exhausted, to the point of death. All agencies that increase the pressure to which the parenchymatous fluids of the tissues are subjected increase the amount of lymph secreted, and conversely. Of this the following observations are illustrative : (a) An increase in blood-pressure, not alone in the entire blood-vessel system, but also in the vessels of the part in question, causes increase in the amount of lymph, and conversely. (b) Ligation or compression of the efferent veins causes considerable increase in the amount of lymph given off by the parts in question, even more than double, because the escape of fluid is confined to the lymphatic vessels. The applica- tion of tight bands is also a cause for swelling of the parts to the peripheral aspect of the application, as copious effusion of lymph takes place into the tissues hypo- static edema. (c) An increased supply of arterial blood acts in a similar manner, but less powerfully. In this connection paralysis of the vasomotor or irritation of the vaso- dilator fibers may cause an increase in the amount of lymph by creating marked hyperemia. The process of dilatation favors the production of lymph in greater degree than permanent distention of the blood-vessels. Contraction of the arterial paths as a result of irritation of the vasomotor nerves or from other causes will naturally have the opposite result; but even after ligation of both carotids, the lymph-current in the large cervical trunk of the dog by no means ceases, as the head is still supplied with blood in small amount by the vertebral arteries. If, after unilateral division of the sympathetic nerve, the blood-vessels of the ear are dilated, indigo-carmine, injected into the blood, enters earliest and in greater degree into the lymph of this ear; the latter also becomes decolorized earlier than the healthy ear. In this way the rare instances of unilateral or partial icterus are to be explained. An increase in the total volume of blood as a result of injection of blood or serum into the veins causes increased formation of lymph, as, in consequence of the increased tension thus induced, blood-plasma passes over into the tissues in large amount. If water or a hypotonic salt-solution be infused, water passes out into the tissues. After death and complete rest of the heart, the formation of lymph still goes on for some little time, although in slight degree. If fresh ORIGIN OF LYMPH. 369 blood be then passed through the animal's body, still warm, increased lymph will in turn flow from the large lymph-trunks. It thus appears that the tissues are still capable of taking up plasma from the blood for the production of lymph for some time after cessation of the circula- tion. This fact may explain the circumstance that some tissues, as, for example, _the connective tissue, appear to contain more fluid after death than during life, while, at the same time, the blood-vessels have after death given up much of the plasma from their interior. Under the influence of curare an increase in the secretion of lymph takes place ; the amount of the solid constituents of the lymph increasing. In the frog large amounts of lymph collect in the lymph-sacs, and this may be due in part to the fact that the lymph-hearts are paralyzed by curare. The production of lymph is increased also in the tissues of inflamed parts. ORIGIN OF LYMPH. SOURCE OF LYMPH-PLASMA. The lymph-plasma is, in part, a filtrate from the blood-vessels, passing over into the tissues, in accordance with the prevailing blood-pressure. In this process, the salts (penetrating membranes most readily) pass through admixed in approximately the same proportions as the salts in the blood-plasma; the fibrin-factors, to about two-thirds; the albumin, about one-half. As in the case of filtration in general, the filtration of lymph also must increase with increased pressure. C. Ludwig and Tomsa were able to demonstrate this by permitting blood- serum to pass through the blood-vessels of an excised testicle under varying pressure, with the result that the transuded fluid from the lymph-vessels was increased or diminished in amount. This artificial lymph exhibited a composi- tion similar to that of natural lymph. The albumin contained in the lymph also increased with increasing pressure. In addition, the metabolic products of the tissues, concerning whose qualitative and quantitative conditions little is known, naturally undergo admixture with the lymph-plasma in the different tissued. In part, however, the formation of lymph must be regarded as a secretory process of the cells of the blood-capillaries. In favor of this view is the fact that materials injected into the blood (sugar, egg- albumin, peptone, urea and sodium chlorid) pass in concentrated form into the increased lymph ; further, that the blood is capable of maintaining the osmotic tension of its plasma. As a result of this secretory property on the part of the endothelium of the vessels, substances that would disturb the isotonia between the blood-corpuscles and the blood-plasma are quickly eliminated from the blood, including superfluous water. After the injection of peptone, the blood-pressure falls enormously, so that the passage into the lymph cannot be dependent upon this pressure. With increase in the lymph-current, the secretion of urine also is later increased. The lymph-paths may thus be considered as a reservoir that temporarily takes up out of the blood the substances to be eliminated, whence they are then gradually further consumed or excreted. According to Heidenhain, there are materials that increase lymph-production, lymphagogues, which are in part effective by causing the passage of fluid from the blood into the lymphatic radicles. Among such agencies are injections into the blood of a decoction of leeches, crab-muscles, mussels, solution of nuclcin, tuberculin, bacterial extracts, bile, physostigmin , pilocarpin and extract of helian- thus. In part they increase the amount of lymph by causing the passage of water from the tissues into the lymph. In this category belong injections into the blood of sugar, urea and salts. Atropin diminishes lymph-production. 24 370 SOURCE OF THE LYMPH-CELLS. Muscular activity causes increased lymph-production, as well as a more rapid escape of the lymph. The tendons and fasciae of the skeletal muscles, which possess numerous small stomata, absorb lymph from the muscular tissue. With alternate contraction and relaxation of these fibrous tissues, their lymph-ducts suck themselves full and propel the lymph onward. Even passive movements are effective in this direction. If solutions are injected beneath the fascia lata, they can be propelled onward by passive movements, contraction and relaxation, into the thoracic duct. SOURCE OF THE LYMPH-CELLS. A considerable portion of the lymph-cells are derived from the lymph- glands, out of which the lymph-stream washes them into the efferent ves- sel. Therefore it happens that the lymph-stream, after passing through the lymph-glands, is always found richer in lymph-cells. Within the lymph-glands there are large and small lymphocytes, the -latter being the daughter-cells of the former, and arising by mitosis. In addition, new leukocytes are constantly migrating from the blood-capillaries of the follicular bands into the reticulum. The lymphatic follicles permit cellular elements to enter through the meshes of their limiting layer into the adjacent small lymph- vessels. A second seat of lymph-cell production is found in the organs contain- ing adenoid tissue as a basis, in the meshes of which lymph-cells are found in large number, such as the entire mucous membrane of the intestinal tract, the bone-marrow and the spleen. The cells reach the radicles of the lymph- vessels in these organs by ameboid movement. Just as the lymph-cells reach the circulation through the large trunks and are there encountered as white blood-corpuscles, so, likewise, numerous leukocytes migrate in turn from the blood-capillaries into the lymph- vessels, especially in their small beginnings, and partly by active ameboid movement, partly by being forced by filtration-pressure exerted by the blood-column. In rare cases even a return movement of lymph- cells from the lymph-spaces into the blood-vessels has been observed. Also particles of cinnabar or milk-globules introduced into the blood reach the lymph- vessels from the blood-capillaries in a short time; the nerves of the vessels having no influence in this condition. In case of venous stasis, in analogy with the processes attending diapedesis, this passage takes place more freely than when the circulation is unembarrassed. Inflammatory changes in the vessel- wall also favor the passage. The vessels of the portal system prove especially permeable. New lymph-cells result also through multiplication by division of the lymph- corpuscles, and likewise of the so-called fixed connective-tissue cells, as has been demonstrated with certainty especially in the pres- ence of inflammation of certain organs. If irritants which excite inflam- mation are applied to the excised cornea, kept in a moist chamber, a large increase in the wandering cells in the anastomosing lymph- passages of the cornea will be noted ; and as, in the inflamed cornea, the corneal cells permit the recognition of a reproduction of their nuclei by division, the conclusion is probably justified that a division of the corneal corpuscles (fixed connective-tissue cells) is responsible for the increase in the wandering cells. That a new-formation of leukocytes must take place by division, as well as by the setting free of divided connective-tissue cells, is shown by their often CIRCULATION OF CHYLE AND LYMPH. 371 enormous production in the presence of inflammations (pus-formation), particu- larly in the case of extensive phlegmons and purulent effusions in the serous cavities, when by reason of their enormous number, they cannot be regarded as having resulted solely by migration from the circulation. The destruction of the lymph-cells appears to take place in part at the seats of origin of the vessels and in the vessels themselves. The occurrence in the lymph of the fibrin-factors, which are derived from disintegrated leukocytes, tends to support this view. Particularly in the presence of severe inflammation, especially in connective tissue, the new-formation of numerous lymph-cells appears to be attended with their increased destruction. Therefore the lymph under such circum- stances becomes especially rich in fibrin, and, naturally, also the blood, through the lymph. According to Hoyer, the lymph-glands are also filtering apparatus in which degenerating leukocytes are intercepted and subjected to a destructive meta- morphosis. CIRCULATION OF CHYLE AND LYMPH. The cause for the movement of the chyle and the lymph depends ultimately on the difference in pressure prevailing between the lymphatic radicles and the points at which the lymphatics empty into the venous system. In detail the following facts are noteworthy : In the onward movement of the lymph, forces are primarily active that are of influence at the points of origin of the lymphatics. These forces must vary in accordance with the character of the points of origin, (a) The lacteals receive the first motile impulse through the contraction of the muscles of the villi. Inasmuch as these grow shorter and smaller, they constrict the axial lymph-space, whose contents must move in a centripetal direction. With the succeeding relaxation of the villus, the numerous valves prevent the chyle from flowing backward. With con- striction 7 of the lumen of the intestine, through contraction of the in- testinal muscles, the villi are forced more closely together longitudinally, the evacuation of the central lymph- vessel being likewise favored, (b) Within those lymph- vessels that originate as peri vascular spaces, every dilatation of the blood-vessels must cause a movement of the surrounding lymph-stream in a centripetal direction, (c) Lymph enters the open lymph-pores of the pleura with each inspiratory movement, which excites suction upon the thoracic duct. A similar condition exists at the orifices of the lymph- vessels on the abdominal aspect of the diaphragm- atic peritoneum. The blood-vessels participate principally in absorption from the abdominal cavity, the lymphatics relatively little. If serous fluid or a solution of salt or sugar is introduced into the abdominal or pericardial cavity, it will be absorbed, and, if isotonic with the blood- plasma, without change; if it is not isotonic, it will first be made isotonic by elimination from the blood. Accordingly, osmosis cannot be alone the active agency in the process of absorption, as imbibition contributes some influence. If the intra-abdominal pressure increases, the blood-vessels absorb more freely, but with excessively high pressure less freely, in consequence of compression of the abdominal veins. In this manner is explained the clinical observation that, in the presence of ascites, absorption is often promoted after the abdominal tension is 372 CIRCULATION OF CHYLE AND LYMPH. diminished through removal of a moderate amount of fluid, (d) In those vessels that arise by means of fine secretory canaliculi, the move- ment will depend directly on the tension of the parenchymatous fluids, and the latter, in turn, upon the tension in the blood-capillaries. Thus the blood-pressure will still be active as a force from behinde ven into the lymphatic radicles. In the lymph-trunks themselves, the contractions of their mus- cular walls propel the current onward. Heller noted, in the lymphatics of the mesentery of the guinea-pig, that this movement was peristaltic in an upward direction. The large number of valves prevent a back- ward current. In addition, the contractions of the surrounding muscles, further, any pressure upon the vessels and the tissues as the seat of origin of the lymphatic radicles will force the current onward. If the escape of blood from the veins is rendered difficult, lymph is poured out more abundantly from the tissues in question. The interposed lymph-glands offer considerable resistance to the current, as the lymph must flow through numerous spaces, traversed by fine meshes and partially filled with cells. Nevertheless the obstacles thus presented are in part compensated for by the numerous unstriated muscles that are present in the sheath and the trabeculae of the glands. By means of these, compression of the glands (as of a sponge) can take place, the presence of the valves again determining the centripetal direction of the current. From this point of view electrical stimulation of swollen lymph-glands might be successful. With the union of the vessels into a few of considerable size, and finally to form the main trunk, the sectional area of the current becomes diminished, and the velocity of the current correspondingly increased. Nevertheless, the velocity under such circumstances is always low, reaching only from 238 almost to 300 mm. in a minute in the main cervical lymph-trunk in the horse, a fact that is indicative of the exceedingly slow movement of the lymph in the small vessels. The lateral pressure in the same situation was from 10 to 20 mm.; in the dog only from 5 to 10 mm. of a dilute soda-solution, but in the tho- racic duct of a horse it was 12 mm. of mercury. . The time required for the passage of the lymph through the walls of the capillaries of the abdomen or of the lower extremity, is about 2 minutes in the dog; for the propulsion of the lymph through the lymphatics of the lower ex- tremity and of the trunk, 3.2 seconds. The respiratory movements have an important influence upon the lymph-stream in the thoracic duct and the right lymphatic duct, as each inspiration conveys the current of lymph, together with venous blood, to the heart, and as a result the tension in the thoracic duct may even become negative. Lymph-hearts. The lymph-hearts containing valves found in some ani- mals, particularly cold-blooded animals, are deserving of consideration. The frog possesses two axillary hearts (above the shoulder near the vertebral column) and two sacral hearts (above the anus near the apex of the sacrum) . They beat, though not synchronously, about 60 times in the minute and contain about 10 cu. cm. of lymph. They contain striated muscle-fibers and are provided with .special ganglia. The posterior hearts pump the lymph into the branches of the communicating iliac vein, the anterior into the subscapular vein. Their pulsation depends in part on the spinal cord, for, as a rule rapid de- struction of trie cord causes cessation of the heart-beat, but pulsations are not rarely observed to continue after removal of the cord. A second normal source ABSORPTION OF PARENCHYMATOUS EFFUSIONS. 373 of excitation of the lymph-hearts is to be sought in Waldeyer's ganglia. Irrita- tion of the skin, the intestine and the blood-heart gives rise to a reflex influence, partly acceleration, partly retardation of the beat, which does not affect the sacrai heart if the coccygeal nerve, which connects the posterior lymph-heart with the spinal cord, is divided. Strychnin-convulsions accelerate the beat, as does also irritation of the spinal cord by heat, while it is diminished by cold. The heart that has ceased to beat in consequence of exposure or of the action of muscarin, but not resting in consequence of destruction of its nerves, can be excited to renewed pulsation by increased filling. Antiar paralyzes the lymph-hearts and the blood- heart; curare, the former only. In other amphibians, two lymph-hearts have been found; and one or two in the ostrich and the cassowary, in some web-footed birds, as well as in the chicken-embryo; in fish they have been found in the tail, as, for example, in the eel, where their pulsation visibly affects the adjacent veins. The nervous system has a direct influence upon the movement of the lymph through innervation of the muscles of the lymphatics, the lymph-glands, and, when they exist, the lymph-hearts. In addition, there are still other special effects of the nerves upon the absorptive activity of the lymphatic radicles. Kiihne noted, after irritation of the corneal nerves, that the corneal cells contracted within their secretory canaliculi. The following observation by Goltz is also interesting in this connection. When this investigator injected a dilute solution of sodium chlorid subcutaneously into the lymph-spaces, he saw that it was rapidly absorbed; it remained unabsorbed, however, after destruction of the central nervous system. Division of the nerves to the extremities also resulted, temporarily, in retarding the absorption. If inflammation was excited in both posterior extremities of a dog, marked edema, together with acceleration of the lymph-stream, appeared in the one in which the sciatic nerve had been divided. If the thigh of a frog is tightly constricted until the circulation ceases, the nerve being preserved, and the part is immersed in water, it becomes greatly swollen (the dead thigh does not swell) ; whence it follows that absorption takes place independently of the existence of the circulation. Division of the sciatic nerve or crushing of the spinal cord (though not mere transverse section or separa- tion of the brain) abolishes absorption. ABSORPTION OF PARENCHYMATOUS EFFUSIONS. Fluids that transude into the tissue-spaces from the blood-vessels, or those that are injected into the parenchyma through a needle, undergo absorption. In this process the blood-vessels participate primarily, and the lymphatics also secondarily. Into the latter, there pass from the clefts and secretory spaces in the connective tissue, even small particles, as, for example, granules of cinnabar and India ink after tattooing of the skin, blood-corpuscles from hemorrhagic extravasations and fat-droplets from the marrow of fractured bones. If all the lymphatics of a part be ligated, absorption still takes place just as rapidly as before. Therefore, the absorbed fluid must have passed through the delicate membranes of the blood-vessels. The opposite observation, that no absorption of parenchymatous fluids takes place after ligation of all the blood-vessels, does not exclude a participation of the lymphatics in the process. of absorption, because, after ligation of all of the blood-vessels, naturally all formation of lymph in the tissues, and consequently any lymph-current, must cease. The absorption of fluids introduced into the tissues artificially, particularly in the subcutaneous cellular tissue (parenchymatous and subcutaneous injection), generally takes place rapidly, as a rule more rapidly than after administration by the mouth. There- fore, subcutaneous injections of drugs in solution are much employed for thera- peutic purposes. Naturally the substances to be injected should not have a destructive, corrosive or coagulating effect upon living tissues. In addition to the great rapidity of absorption, subcutaneous injection has the further advantage over the administration of a drug by the mouth that some agents that are ingested undergo decomposition in the stomach and intestine as a result of the digestive 374 LYMPH-STASIS AND SEROUS EFFUSIONS. process, so that they cannot at all be absorbed unchanged. Thus, particularly poisons that act through ferments, such as snake-venom, ptomains and putrid poisons, are destroyed by the stomach. Emulsin also behaves in the same manner. If this ferment is introduced into the stomach while amygdalin is injected into a vein of the same animal, poisoning by hydrocyanic acid does not take place, because the emulsin is destroyed by the digestive process. If, however, emulsin is injected into the blood and amygdalin into the stomach, hydrocyanic-acid poison- ing takes place rapidly, because amygdalin is absorbed unchanged from the stomach. Amygdalin is a glucosid (C 20 H 27 Np n ) that breaks up as a result of the fermentative activity of fresh emulsin with the taking up of water, 2 (H,O) , into hydrocyanic acid (CHN), oil of bitter almonds (C 7 H 6 O) and sugar, 2(C 6 H 12 O 6 ). For observations on animals on the absorption of solutions from the parenchyma- tous structures, either poisons whose action gives rise to conspicuous tonic symp- toms, or such harmless substances as are readily discoverable in the blood and subsequently especially in the urine are employed, as, for example, potassium ferrocyanid. The author, in 1878, demonstrated that serum, injected into the subcuta- neous tissue, is rapidly absorbed. The serum, which must be obtained from an animal belonging to the same species or at least as indifferent as possible, undergoes decomposition in the circulation, so that the production of urea in- creases. Infusions of serum may, therefore, be given for nutritive purposes. Febrile reaction is observed after such injections, as in the case of transfusion. Solutions of albumin and peptone, oil, butter, dextrose, levulose, galactose and maltose in solution have also been observed to undergo absorption. LYMPH-STASIS AND SEROUS EFFUSIONS. If obstruction to the efferent venous and lymphatic paths of an organ arises, stasis results, and later abundant effusion of lymph into the tissues. This is most distinctly recognizable in the skin and the subcutaneous tissue, where the soft parts become swollen; while, without redness and pain, tumefaction develops, with a doughy feeling, and pressure with the finger causes pitting. These are the signs of lymph-stasis, which, if the fluid is especially rich in water, is designated by the term edema. Also within the serous cavities, under like conditions, a similar collection of lymph takes place. If numerous leukocytes migrate from the delicate blood- vessels into such serous cavities and undergo multiplication, the fluid, richer in cells, becomes more and more like pus. The multiplication of these cells gives rise to the presence of a considerable amount of albumin, which may subsequently be increased by absorption of water from the effusion. The latter will be made particularly easy when the pressure in the fluid exceeds that in the small blood- vessels. These sero-purulent effusions not rarely undergo a change in constitu- tion later on, for which no reason has been found. The substances present are in part products of the decomposition of albumin, such as leucin and tyrosin, in part products of the retrogressive metamorphosis of nitrogenous substances, such as xanthin, kreatin, kreatinin (?), uric acid (?) and urea. Further, endo- thelial cells from the serous cavities; sugar in pathological serous and chylous effusions and edematous fluid have been found; in the latter also diastatic fer- ment, often cholesterin; and in the fluid of serous hydrocele and echinococcus- cysts, succinic acid. f Not only the pressure from without upon the lymphatics, but, in general, resistance of any kind that is present in the lymph-path may give rise to lymph- stasis and serous effusions. Thus, lymph-stasis results from occlusion of the lymph- atics in consequence m of inflammation and thrombosis (lymph-coagulation) ; further, as a result of impermeable, swollen, inflamed or degenerated lymph-glands. In these cases, however, the formation of new lymph-vessels is frequently ob- served,' reestablishing the former communication. An effusion of lymph may also take place into the serous cavities of the abdomen or the thorax, from rup- ture of large lymph-paths, especially of the thoracic duct chylous ascites or chylothorax. Interference with or even removal of all those factors that have been found active in propelling the lymph onward will be capable of inducing lymph-stasis. If stagnation of lymph can develop in this manner also on the part of the lymphatic apparatus, the appearance of considerable amounts of watery lymph, in the form of edema or anasarca, as well as of serous effusions, is often at the same COMPARATIVE. 375 time due to the fact that a copious transudate is furnished on the part of the blood- vessels. Obstruction in the distribution of the lymph-stream may then further increase such a collection of fluid. Particularly the vessels of the abdomen and, further, those that furnish a watery exudation also under normal circumstances appear, above all others, to be especially adapted to transudation. Such increase in transudation is favored by (i) any considerable degree of venous stasis. These hypostatic transudates are, as a rule, deficient in albumin and leukocytes, but, on the other hand, the richer in erythrocytes the greater the interference with the flow of venous blood. Ranvier induced hypostatic edema artificially in the lower extremity by ligation of the inferior vena cava and simultaneous division of the sciatic nerve. The paralytic dilatation of the vessels of the posterior extremity, induced by the latter, causes an increase in the amount of blood present and a rise in the blood-pressure, which, in turn, promotes edematous exudation. (2) Further, as yet unknown physical changes in the protoplasm of the endothelial cells of the blood-vessels and capillaries may render these capable of permitting the abnormal passage of albumin, hemoglobin and even blood-cells. This takes place when foreign matters are present in the blood in considerable amount, as, for example, hemoglobin in solution; further, when the blood is deficient in oxygen or albumin. Also after exposure to abnormal heat, a similar condition has been observed, and the tumefaction of the soft parts in the vicinity of inflamed tissues likewise appears to be due to an exudation of lymph through altered vessel-walls. Perhaps a nervous influence, which makes itself felt in a certain vascular area (by contraction or relaxation of the protoplasm of the blood-capil- laries ?) , may even be capable of causing such a transitory change in the vessel- walls. Lymphatic transudates of this character are generally rich in cells and consequently also in albumin. (3) Further, the presence of a large amount of water in the blood will increase its capacity for transudation. Nevertheless, the fact should be considered in this connection that the large amount of water contained in the blood acts, in turn, by inducing changes in the protoplasm of the endothelium of the blood-vessels and capillaries, so that it is itself, when long continued, a factor that increases the permeability of the vessel-walls. Debilitated, poorly nourished, flabby individuals particularly exhibit watery lymphatic exudations from watery blood cachectic edema. There is no doubt that lymph-stasis (hydrops) may develop also under cer- tain circumstances, and even through the action of microorganisms (bacterium lymphagoguni) , in consequence of the fact that irritation of the cells of the blood- capillaries (as by the products of metabolism of that organism) gives rise to increased exudation of fluid. COMPARATIVE. Extensive lymph-spaces, lined with endothelium, are present in the frog, beneath the entire external integument. In addition, a large lymphatic space, the cysterna lymphatic magna of Panizza, extends in front of the vertebral column, separated from the abdominal cavity by the peritoneum. Tailed amphibia, as well as many reptiles, have large lymph-spaces beneath the skin, occupying the entire length of the trunk in the lateral regions of the back. Further, all reptiles and the tailed amphibia possess, in the course of the aorta, large, longi- tudinal lymph-reservoirs. Tortoises likewise have an extensive lymphatic ap- paratus (Fig. 130, A, II). The bony fish have longitudinal lymph-trunks in the lateral regions of the back, from the tail to the anterior fins, and these are connected with dilated lymph-spaces at the root of the tail and the fins of the extremities. Within the interior of the body the extensive lymph-sinuses attain their greatest development in the region of the gullet. Many birds possess a sinus-like dilatation of a lymph-space in the region of the tail. In the carnivora the mesenteric lymph-glands are united to form a large, compact mass, the so- called pancreas of Aselli. Naturally the lymph-spaces (provided with valves) always communicate with the venous system, and usually with the territory of the superior vena cava. HISTORICAL. Although the lymph-glands were known to the school of Hippocrates, espe- cially through their morbid enlargement, and although Herophilus and Erasistratus had observed the milk-white chyle-vessels in the mesentery, Aselli (1623) was the 376 HISTORICAL. first to study the mesenteric chyle-vessels more thoroughly, together with their valves. Pecquet (1648), as a student, found the receptacle for the chyle, Rudbeck and then Thorn. Bartholinus the clear, watery lymph-vessels (1650-1652). Eus- tachius (1562) was familiar with the thoracic duct, which Gassendus (1654) later claimed to have been the first to discover. Lister noticed that chyle was colored blue after the injection of indigo into the intestine (1671). Rudbeck (1652) observed the separation of fibrin in the lymph; Reuss and Emmert(iSoy) were the first to observe the lymph-corpuscles. The chemical examinations date from the first quarter of the nineteenth century, and were made by Lassaigne, Tiedemann, Gmelin and others, of whom the latter also recognized the fact that the white color was dependent upon the fat-granules. PHYSIOLOGY OF ANIMAL HEAT. SOURCES OF HEAT. The heat of the body is a form of kinetic energy appearing without interruption and must be conceived as depending upon vibrations of the atoms of the body. In the last analysis every source of heat is contained in the mass of potential energy taken into the body as food, in combination with the oxygen obtained from the air in the act of respiration. The amount of heat liberated depends upon the amount of potential energy transformed. The potential energy of nutrient matters may be appropriately desig- nated as latent heat, inasmuch as it may be conceived that in their consumption in the body, which is essentially a process of combustion, kinetic energy is transformed only in the form of heat. As a matter of fact, mechanical energy and electricity are also developed from the potential energy supplied. However, in order to obtain a uniform measure for the forces transformed, it is advisable to express all potential energy in terms of heat-units. The calorimeter is an apparatus with the aid of which the amount of potential energy contained in food-stuffs can be converted experimentally into heat and the units of the latter can at the same time be measured. Favre and Silbermann employed the so-called water-calorimeter (Fig. 133). A cylindrical box, the so-called combustion-chamber (K), serves for the recep- tion of the substance to be burned. This box is suspended in a larger, cylindrical vessel (L), which is filled with water (w), so that the combustion-chamber is completely surrounded thereby. Three tubes enter into the upper portion of the chamber: one (O) is intended for the passage of air containing oxygen, which is necessary in the process of combustion. The second tube (a) in the middle of the cover is closed above with a thick glass plate, upon which is mounted at an angle a mirror (s) , which permits the observer (B) to look into the interior of the chamber from a lateral point of view in the direction b b. in order to observe the process of combustion at c. The third tube (d) is employed only when it is desired to consume combustible gases in the chamber and through it these are then passed. Generally this tube is closed by a cock. A lead pipe (e e) also passes out of the upper portion of the chamber and in a convoluted arrangement traverses the volume of water, finally reaching the surface at g. Through this the gases of combustion escape, being cooled in the convoluted tube to the tem- perature of the water. The cylindrical vessel containing the water is covered with a lid having open- ings for the four tubes that pass through it. The water-cylinder stands upon legs within a larger cylinder (M), which is filled with a poor conductor of heat. Finally this is placed in a still larger cylinder (N), which again contains water (W) . This last layer of water is intended to prevent any heat from the exterior from raising the temperature of the water in the interior. A definite amount of the material to be examined is burned in the combustion-chamber. After com- bustion has been completed, during the progress of which the water in the interior is repeatedly stirred, the temperature of the water is determined by means of a delicate thermometer. If the amount of increase in temperature is noted, and if the amount of water in the inner cylinder is known, the number of heat-units furnished by the combustion of the measured amount of the substance under examination can be readily estimated. 377 378 SOURCES OF HEAT. Instead of the water-calorimeter the ice-calorimeter may be employed. In this instrument the inner container is surrounded with ice instead of with water. Around this in a second container is still more ice, which prevents any heat from without acting upon the ice in the interior. The body in the interior cham- ber gives off heat and causes a portion of the surrounding ice to melt, while the ice-water passes off below through a tube and is measured. In this connection it should be noted that 79 heat-units are required to melt i gram of ice into i gram of water at a temperature of o C. For animal experimentation the calor- imeter has probably reached the highest grade of perfection at the hands of Rubner. The air-calorimeter of d'Arsonval permits of measurement in human beings within a few minutes. A rigid cylinder of woolen material, within which a man may stand, is provided above with a chimney. If the man heats the air in the interior, this will escape through the chimney and set in motion a small wind- mill contained therein, whose revolutions can be counted. The amount of heat given off is proportional to the square of the velocity of the escaping cur- rent of air. A man in the nude state yielded 124, and in the dressed state 79 calories in an hour. Just as in the calorimeter, though much more slowly, nutrient mat- ters are consumed in the human body with a supply of oxygen, and as a consequence there takes place a transformation of potential into kinetic energy, which in a person at rest appears almost wholly as heat. Favre and Silbermann, Frankland, Rechenberg, Stohmann, B. Danilewsky, Jlubner and others have made calorimetric observations as to the amount of heat yielded by the combustion of many nutrient substances. One gram of water- free substance yields in heat-units as follows: CARBOHYDRATES. Proteids on the average, ........ S7 11 Galactose, .................... 37 22 Serum-albumin, ............... 5918 Cane-sugar, ................... 3955 Egg-albumin .................. 5735 Milk-sugar, .................... 395 2 Syntonin, ..................... 598 Maltose, ...................... 3949 Hemoglobin, ..... .............. 5885 Glycogen, ..................... 4191 Milk-casein, ................... 5858 Starch, ....................... 4183 Yolk of egg, . . . : ............... 5841 Cellulose, ..................... 4185 Vitellin, ....................... 5745 Cow's milk, ................... 5613 M _ af f 5663 Woman's milk .................. 5786 \ 5641 Rye-bread ..................... 4471 Peptone, ...................... 5 2 99 Wheat-bread, ................. 43 5 1 Fibrin, ........................ 5637 Peas .......................... 4889 Vegetable fibrin, ............... 594 2 Buckwheat, ................... 4288 Legumin, ..................... 5793 Maize, ........................ 5188 Conglutin, .................... 5479 Alcohol, ...................... 6980 Muscle-extractives, ............. 4400 Animal fats on the average, ..... 9500 Liebig's meat-extract ........... 3216 Butter 9 2 3i (Principally according to Stoh- Olive-oil, '.'.'.'.'.'.'.'.'.'. '.'.'.'.'.'.'.'.'.'.'/ 9*7 mann >- ' ( 900 T> ., Ra P e - 011 ' 9627 Urea ......................... 2 537 9759 Glycin, ................... .... Stearic acid, ................... 2712 Leucin, ....................... 6533 Oleic acid, .................... 2682 Hippuric acid, ................. 5678 Palmitic acid, ................. 2398 Kreatinin, ..................... 4275 Glycerin, ..................... 397 Uric acid, ........... . ......... 2 74* Alcohol, ...................... 7 100 As the proteids in the body are not transformed beyond urea the amount of heat resulting from the combustion of urea is to be deducted from that resulting from the combustion of the proteids. As one gram of proteids (average calories 5711) yields 0.3428 gram of urea, and i gram of urea yields 2537 calories, 870 calories are to be deducted. Isodynamic food-stuffs, namely, those that yield the same amount of heat in the process of combustion, are as follows: 100 grams of animal proteid, after deduction of the heat resulting from the combustion of urea, equal 52 grams of fat, 114 grams of starch, 128 grams of dextrose. One hundred grams of fat are SOURCES OF HEAT. 379 isodynamic with 243 grams of dry meat or 225 grams of dry syntonin, or with 256 grams of dextrose. According to Pfliiger, i gram of nitrogen in meat equals 2.79 grams of fat; i gram of animal fat equals 0.364 gram of nitrogen in meat; i gram of starch equals 0.424 gram of fat or 0.154 gram of nitrogen in meat; i gram of grape-sugar equals 0.390 gram of fat or 0.42 gram of nitrogen in meat; too grams of vegetable albumin likewise equals 55 grams of fat or 121 grams of starch or 137 grams of dextrose. Rubner estimates in human beings on a mixed diet the available heat -pro- ducing energy for i gram of proteid at approximately 4100 calories, for i gram of fat 9300 calories, for i gram of carbohydrate 4100 calories. For the dog Rubner determined that i gram of nitrogen in the excreta of the fasting animal had caused the production of 25,000 calories; further, that i gram of nitrogen in the excreta with a meat-diet had produced 26,000 calories; and i gram of carbon, formed from 1.3 grams of fat, had yielded 12,300 calo- ries. If it be known, therefore, how many parts by weight of the foregoing substances a human being takes up with his food during twenty-four hours, the calculation can be made as to how many heat- units he may generate there- from through oxidation. In this connection the utiliza- tion of the nutrient materials must be taken into consider- ation, in accordance with which a certain, even though small, percentage of the food cannot be disposed of by the digestive and absorptive or- gans, and therefore is ex- creted unused. Rubner found that, however abundant the administration of food, a larger amount of heat can be shown to be produced immediately on the first day of feeding, as compared with the preceding days of fasting. The bodily temperature under such circumstances remains unaltered. The greatest amount of heat is produced as a result of excessive administration of proteids, less from carbohydrates and least from fats. In detail the sources of heat are as follows : i. The transformation of chemical combinations of foods with high potential energy into those of lesser or completely exhausted potential energy. As the organic articles of food, exclusive of the inorganic accompaniments, consist of C, H, N and O, it is especially through (a) the combustion of C into CO 2 and of H into H 2 O that heat is produced. In this connection it is to be noted that the combustion of i gram of C into C0 2 yields 8080 heat-units, while that of i gram of H into H 2 O yields 34,460 heat-units, though the C and H in the molecules of the food-stuffs must not already be saturated with O. The amount of necessary for this purpose is taken up in the act of respiration. There- FIG. 133. Water Calorimeter (after Favre and Silbermann). 380 SOURCES OF HEAT. fore an approximate estimate may be made as to the quantity of heat produced by an organism from the amount of oxygen consumed in a unit of time. An equal consumption of O corresponds with an equal production of heat, whether it served for the oxidation of H or of C. As a matter of fact, a relation exists between heat-production in the animal body and the consumption of O, as between cause and effect. Thus, cold-blooded animals, which consume little O, have a low bodily temperature. Among warm-blooded animals i kilogram of living rabbit takes up 0.914 gram of O within an hour and by this means maintains its bodily temperature on the average at 38 C.; i kilogram of living hen, on the other hand, consumes 1.186 grams of O in an hour and maintains as a result an average temperature of 43.9 C. The amount of heat produced is equally large whether the combustion takes place slowly or rapidly. The activity of metabolism has, accordingly, an in- fluence only upon the rapidity, but never upon the absolute amount, of heat-formation. Also, the combustion of inorganic substances in the body, such as that of sulphur into sulphuric acid, that of phosphorus into phosphoric acid, constitutes a source of heat, although it be but slight. According to Rubner this amounts to but 0.47 per cent, of the heat. (b) In addition to the processes of combustion, however, all of those chemical processes in the human body, as a result of which the total amount of potential energy present is diminished, in consequence of greater saturation of affinities of the atoms previously present, are attended with the development of heat. Wherever the atoms combine with saturated affinities for greater stability in their ultimate position of rest, chemical potential energy is transformed into kinetic thermal energy, as, for instance, in the alcoholic fermentation of grape-sugar and other similar processes. Heat is produced also in the following chemical process : () The union of bases with acids. Here the character of the base determines the amount of heat formed, while the character of the acid is without any influence. Only when the acid, as, for instance, carbon dioxid, is not capable of neutraliz- ing the alkaline reaction, is the production of heat smaller. Also, the forma- tion of chlorin-combinations, as in the stomach, generates heat. (-3) The transformation of a neutral into a basic salt. In the blood the sulphuric and phosphoric acids resulting from the combustion of sulphur and phosphorus combine with the alkalies of the blood to form basic salts. The decomposition of the carbonates of the blood by lactic and phosphoric acids constitutes a double source of heat, namely through the formation of a new salt, as well as through the release of carbon dioxid, which is in part absorbed by the blood. (>-) The combination of hemoglobin with oxygen. According to Berthelot the amount of heat produced in this way is equal to one-seventh of the total amount formed in the body. In the chemical processes through which the body is provided with heat there not rarely occur heat-absorbing intermediate transformations of the bodies. At times, in order to bring about more complete saturation of the affinities, inter- mediary atom-groups in themselves firmly united must first be broken up. In this process thermal energy is consumed. Also in the breaking up of stable aggregate states in processes of retrogressive metamorphosis heat is bound up. All of these intermediary losses of heat, however, are extremely slight as compared with that due to the development of the end-products. 2. Physical processes may be mentioned as a second source of heat, (a) The transformation of the kinetic mechanical energy of the viscera furnishes heat, as the work done cannot be conveyed to the outside. ANIMALS WITH CONSTANT AND VARIABLE TEMPERATURE. 381 Thus, all of the kinetic energy of the heart is transformed into heat through the resistance opposed to the blood-stream. The same may be said of the kinetic energy of certain muscular viscera. Thus, the torsion of the costal cartilages and the friction of the current of air in the respiratory organs and of the contents of the digestive tract yield a certain amount of heat. Small amounts of the mechanical energy of the heart are transmitted through the apex-beat and the superficial pulse to surrounding parts, but these are ex- ceedingly small. Also, in the respiratory movement, in the expulsion of the respiratory gases, the expectorated and other matters, a small amount of energy is conveyed to the outside, which is not converted into heat. Joule has attempted to determine the amount of heat generated in consequence of the kinetic energy lost by a flowing fluid. According to him the amount of heat produced in this way as a result of the friction must stand in a relation to the product of the difference between the initial and the terminal pressure in the weight of the flowing fluid mass. If it be assumed that the daily work of the circulation equals more than 86,000 meter-kilograms, it will be seen that the resulting amount of heat in 23 hours will be about 204,000 calories, which is suffi- cient to raise the temperature of the body of a medium-sized person about 2 C. (6) If the body through muscular activity does work transmitted to the outside, as, for instance, if an individual throws a heavy weight or ascends a tower, a portion of the kinetic energy is converted into heat through the friction of the muscles, the tendons, the articular surfaces, further through concussion and pressure of the ends of the bone upon one another. (c) The electrical currents generated in muscles, nerves and glands, apart from the small amounts that pass outside of the body with suitable conduction, are most probably transformed into heat. Thermogenic chemical processes also generate electricity, which likewise is trans- formed into heat. This source of heat is, however, quite insignificant. (d) As a further slight source of heat from physical causes there should yet be mentioned heat-production through absorption of carbon dioxid, through the condensation of water in its passage through membranes, and in the process of imbibition, the formation of stable aggregate states, as, for instance, of cal- cium in the bones. It is true, heat is again in part lost through the involution of solid parts at advanced age. After death, at times also under pathological conditions during life, coagulation of blood and the rigidity of muscles constitute in this manner a source of heat. ANIMALS WITH CONSTANT AND WITH VARIABLE TEMPERATURE. Instead of the older division of animals into cold-blooded and warm- blooded (mammals and birds), it is advisable to base their classification upon another characteristic, namely, the uniformity or the variability of the bodily temperature with respect to external influences. For the class of warm-blooded animals the name homoiothermic animals has been introduced by Bergmann, because they are capable of maintaining their bodily temperature with remarkable uniformity notwithstanding consid- erable variations in the surrounding temperature. He designated cold- blooded animals poikilothermic animals because their bodily temperature rises and falls within wide limits in accordance with the temperature of the surrounding medium. Accordingly, heat-production must be in- creased in homoiothermic animals if exposed for a long time in a cold atmosphere and diminished on exposure for a long time in a warm atmosphere. 382 METHODS OP ESTIMATING THE TEMPERATURE. An instance of this great constancy of the temperature in the human body was furnished by Fordyce, who died in 1792. After a man had been for ten minutes in a room filled with hot, dry air, the temperature of the interior of his closed hand, the cavity of his mouth beneath the tongue, as well as the urine, was raised only a few tenths of a degree. When Becquerel and Brechet were inves- tigating by means of the thermo-electric needle the temperature in the middle of the biceps muscle in a man whose arm had been immersed for a whole hour in ice-water, they found the temperature of muscular tissue reduced only 0.2 C. The same muscle exhibited either no increase in temperature or a reduction of only 0.3 C. after the man had immersed the arm in water at a temperature of 42 C. for a quarter of an hour. If marked alteration in temperature be brought about by powerful agents, namely, by vigorous abstraction of heat or by considerable addition of heat, great danger to the continuance of life results. Poikilothermic animals react differently, the bodily temperature following in general the surrounding temperature, though with varia- tions. On the basis of numerous observations Soetbeer therefore states that the poikilothermic vertebrates have no special temperature in the ordinary sense of the term, but their bodily temperature, like that of inanimate objects, is dependent upon that of the physical conditions of their surroundings. The following may suffice as illustrations of the bodily temperature in the animal kingdom: Birds: sea-gull, 37.8 C.; swallow and titmouse, 44.03; mam- mals: dolphin, 35.5, mouse, 41.1, echidna from 26.5 to 36; arthropods: from 0.1 to 5.8 above the surrounding temperature; in bees aggregated in the hive from 30 to 32, and in bees in swarms as high as 40. The following animals raise their temperature above the surrounding temperature: cephalopods 0.57, molluscs 0.46, echinoderms 0.40, medusae 0.27, polyps 0.21 C. METHODS OF ESTIMATING THE TEMPERATURE: THERMOMETRY. Thermometry. By means of thermometric apparatus information is obtained as to the temperature of the body subjected to examination. For this purpose there are employed: The thermometer (Galileo, 1603). Sanctorius was the first in 1626 to make thermometric measurements in human beings. It is advantageous to employ instruments ^ graduated in 100 parts according to Celsius, each degree being subdivided into ten parts. The apparatus should be compared with a nor- mal thermometer before being used. The column of mercury should be slender and the spindle neither too small nor too large, and preferably cylindrical in shape. A large bulb increases the sensitiveness and also the period of observation, because the large amount of mercury is influenced through and through by heat with greater difficulty. If the spindle be smaller the observation can be made more rapidly, but it is less trustworthy. The scale should be of porcelain. All thermometers acquire an error after use for a considerable time, regis- tering too high. Therefore, they should be compared from time to time with a normal instrument. At every observation the bulb should be completely sur- rounded and kept at rest for at least fifteen minutes and during the last five minutes no movement in the column of mercury should be noticeable. Minimal and particularly maximal thermometers, for the measurement of febrile tempera- ture, are of the greatest convenience to the physician. For delicate comparative measurements Walferdin's metastatic thermometer (Fig. 134) is especially useful. The tube is exceedingly narrow in proportion to the bulb. In order that on this account the instrument should not be drawn out to an extraordinary length, an arrangement is provided by which the necessary amount of mercury can be increased or diminished at will. So much mercury is taken that at the expected temperature the column reaches about to the middle of the tube. This end is attained by having at the upper extremity of the tube an expansion in which the superfluous mercury is received. If, for instance, a temperature is to be taken that is likely to be between 37 and 40 C., the bulb METHODS OF ESTIMATING THE TEMPERATURE. 383 X is first heated to somewhat above 40 C.; then it is copied quickly and at the same time shaken, so that the column of mercury is broken below the upper expansion. Thus the play of the column is from about 40 downward. The tube is so fine that i C. com- prises about 10 cm. in length, and yi^ C. is still i mm. long. A reading of even as little as T ^oo C. has been made possible. The scale is graduated arbitrarily. The value of the graduation must be determined by comparison with a normal thermometer, and also the temperature when the column of mercury reaches a certain level. Kronecker and Mayer caused small maximal thermometers to be passed through the digestive canal or through vessels of considerable size. The small instruments are so-called outflow thermometers, whose mercury escapes through the short open tube, and in greater amount naturally when the temperature is highest. After removal, examination is made by comparison with a normal thermometer for the purpose of determining the tem- perature at which the mercury rises exactly to the free extremity of the tube. The thermo-electric apparatus permits rapid and accurate measurement of the temperature (Fig. 135, I). The thermo-elec- tro-galvanometer of Meissner and Meyerstein employed for this purpose contains a circular magnet (m) suspended from a silk thread (c) to which by means of a hook a small mirror (s) is attached. Near this magnet another bar-magnet is fixed, with its poles similarly directed, and in such proximity that the free magnet is capable of turning to the north with the slightest de- gree of force. About the latter a thick copper wire (b b) is wound several times (in the diagrammatic representation but one turn is shown), and with the prolonged extremities of this two needle-like thermo-elements (a f , f a) made of different metals German silver and iron and soldered together, are connected. The free ends of these needles of similar name are, further, con- nected by means of a wire (b) . Thus the two thermo-elements are incorporated into the closed circuit. At a distance of three meters from the mirror a horizontal scale (K K) is fixed, the numbers on which are reflected in the mirror. The scale itself is supported upon a telescope (F) , which is directed toward the mirror. The observer (B), looking through the telescope, sees in the mirror the figures of the scale, which can be accurately adjusted. If the magnet swings out of the magnetic meridian, and with it the mirror, other figures on the scale appear to the observer in the mirror. If one of the thermo-elements is heated, an electric cur- rent results, which is directed in the warmer element from the German silver to the iron, and at the same time causes deflection of the movable magnet. If the observer conceive that he is swimming in the direction of the current within the conducting wire the north pole of the magnet is deflected to the left. The tangent of the angle, through which the freely movable magnet is deflected from its position of rest in the magnetic me- ridian by means of a galvanic current passed before it, is equal to the relation of the galvanic energy G to the magnetic energy. Therefore, the tangent is as G is to D. In order, thus, to keep the tangent as large as possible, while G remains the same, the magnetic energy must be reduced as much as possible. If the magnetism of the swinging magnet be designated m and the mag- netism of the earth T the magnetic energy D equals Tm. From this it appears that D can be diminished in two ways, namely (i) by reduction of the magnetic force of the swinging magnet, as may be done through the astatic pair of needles of the Nobili multiplicator, and (2) by lessening the magnetism of the earth by means of a fixed auxiliary magnet (Hauy bar) applied in the neighborhood of the swinging magnet with the same object. Of importance for the rapid and accurate adjustment of the magnet is the employment of the so-called damping arrangement of Gauss, which is not indicated in the illustration. This consists of a thick, FIG. 134 Wal- ferdin's Me- tastatic Ther- mometer. METHODS OF ESTIMATING THE TEMPERATURE. copper, hollow cylinder, upon which the wire of the coil is wound. This mass of copper may be considered as a closed multiplicator of a single winding with a large cross-section. The magnet set into oscillation induces in this closed copper mass a current whose intensity is greatest when the rapidity of oscillation of the magnet is greatest, and which takes the opposite direction as soon as the mag- net is reversed. In lesser degree the multiplicator itself as soon as it is closed operates in the same manner as a damper. The currents thus induced cause a reduction in the oscillations of the magnet in such a way that the arc of move- FIG. 135. Diagrammatic Representation of Thermo-electric Apparatus for the Measurement of Temperature. ment diminishes in rapid and almost geometric progression. The induced, damp- ing current is the stronger the less the resistance in the closed circuit, in the presence of the damper therefore the greater the transverse section of the copper ring. By means of this damping arrangement the monotonous oscillation of the magnet to and fro is limited and the latter comes to rest rapidly and promptly after three or four small oscillations while the observation is sharp and made without loss of time. So-called Dut rochet needles (II) are introduced as thermo-electric elements. These consist of German silver and iron and are soldered together longitudinally TEMPERATURE-TOPOGRAPHY. 385 at their points. Becquerel needles (III) also may be employed. These are made of the same metals, which are soldered together in continuity. The needles must be well covered upon their surface with brown varnish in order that the currents resulting from the moistening of different metals with the parenchymatous fluids may not interfere with the thermo-currents obtained. Before the investigations are undertaken the extent of deflection on the scale to which a definite difference in temperature in the needles gives rise, thus about i C., must further be deter- mined. In order to do this a sensitive thermometer is fastened by means of a loop to each of the thermo-needles, which are placed in separate oil-baths of a constant temperature, though differing by i C., as can be seen from the ther- mometers. If the circuit is now closed the deflection on the scale will naturally correspond to i. If, thus adjusted, the instrument exhibited a deflection of 150 mm., every displacement of the scale of i mm. would equal T i ff C. If this has been determined, either the two thermo-needles can be introduced into the different tissues or organs of animals at the same time, and in this way information be gained as to the prevailing differences in temperature in these portions of the body; or one of the thermo-needles is placed in a bath of constant temperature approximately that of the body in which at the same time there is a sensitive ther- mometer, while the other needle is introduced into the viscus to be examined. In this event the difference in temperature between the tissue and the constant source of heat is learned. For slight differences in temperature, such as usually exist in the tissues of the body, the thermo-electric energy is always proportionate to the difference in temperature between the two needle-elements. It is obvious that instead of one pair of needles a multiplicity may be em- ployed. By this means the delicacy of the apparatus naturally is materially in- creased. Thus, v. Helmholtz was able to increase the delicacy of the apparatus to the detection of differences of ^Vcr C. by the employment of 16 antimony- bismuth elements? Schiffer constructed a thermopile of four pairs of needle- elements in a simple manner (Fig. 135, IV) by soldering together alternately wires of iron and German silver. It is intended that four such elements should be introduced into two substances (A and B) to be examined for differences in tem- perature. Thermo palpation is the name given by Benczur and J6nas to the following method of examination : If the finger be moved over an uncovered portion of the trunk it will be found that the skin is warmer over parts containing air, such as lungs and intestines, than over parts, normal or pathological, not containing air. The boundaries are said to agree with those determinable by percussion, but this has been disputed. Naturally this difference can be established also by thermometric examination. TEMPERATURE-TOPOGRAPHY. Although a powerful influence must be ascribed to the blood, on account of its constant movement, in the equalization of the temperature in the different parts of the body, nevertheless an exact equalization is never attained, but noteworthy differences exist in different parts of the body. The temperature of the skin has been found to be as follows : In the middle of the sole of the foot 32 .26 C. J. Davy made these measure- In the vicinity of the Achilles tendon ... 33.85 C. ments immediately on In the middle of the anterior aspect of arising without dressing, the leg 33-5 C. with the temperature of In the middle of the calf 33 .85 C. the room at 21. Only In the popliteal space 35 C. the inferior surface of the In the middle of the thigh 34-40 C. bulb of a thermometer In the inguinal fold 35-8o C. otherwise covered came in Over the apex-beat of the heart 34-40 C. contact with the different On the face in a man 31 C. portions of the skin. At the tip of the nose and on the lobule of the ear from 22 to 24 C. In the closed axillary cavity, the temperature ranges, according to Wunderlich, from 36.49 to 37.25; according to C. v. Liebermeister it is 36.89 C. 25 386 TEMPERATURE-TOPOGRAPHY. The skin overlying muscles is warmer than that covering bones and tendons. The cutaneous temperature is somewhat lower in the aged, while in children it ranges between 25 and 29 C. The skin of the cranial vault fcas a higher temperature in the frontal and parietal regions than in the occipital region. Further, the left side is warmer than the right. The temperature of the skin is increased by dyspnea. v. Liebermeister employs the following method in taking the temperature of free cutaneous surfaces : The bulb of the thermometer is heated to a point slightly above that of the temperature expected. Then the fall of the column of mercury is observed as the instrument is held in the air, and then at the apparently appro- priate moment the bulb is applied to the surface of the skin. If the skin has the same temperature as the bulb, the mercury must remain stationary for a time. For the measurement of the cutaneous temperature, it is useful to employ a spe- cially constructed thermometer with a flat vessel. The temperature of the cavities of the body : Cavity of the mouth beneath the tongue 37- I 9 C. Rectum 38.01 C. Vagina . . 38.03 C. The temperature of the uterus is somewhat higher, while that of the cervical canal is somewhat lower. Urine 37.3oC. The temperature of the stomach falls during the process of digestion. Cold rectal injections (11 C.) rapidly lower the temperature of the stomach i C. The temperature of the blood is on the average 39 C. In the internal portions of the body venous blood is warmer than arterial blood, while the reverse condition prevails in the peripheral portions. Blood of the right heart 38.8 C. ] Blood of the left heart 38.6 C. [ P1 , R A Blood of the aorta 38.7 C. [Claude Bernard. Blood of the hepatic veins 39-7 C. J Blood of the superior vena cava 36.78 C. 1 Blood of the inferior vena cava 38.11 C. \ G. v. Liebig. Blood of the crural vein 37.20 C. J The lower temperature of the blood in the left heart is due to the fact that the blood is cooled in the lungs in the process of respiration. According to Heiden- hain and Korner the temperature of the right heart is somewhat higher because it lies upon the warm liver, while the left heart is surrounded by the air-containing lung. This fact, observed by Malgaigne in 1832 and by Berger and G. v. Liebig, is disputed by others, who attribute the somewhat higher temperature of the left heart to the fact that more active processes of combustion take place in arterial blood and that heat is generated in the formation of oxyhemoglobin. In adjacent veins or in those of the same name the temperature of the blood is generally lower than in the corresponding arteries, on account of the greater amount of heat given off in the slower movement. Thus, the temperature of the blood of the jugular vein is from 0.5 to 2 lower than that of the carotid; that of the blood of the crural vein is from 0.75 to i lower than that of the crural artery. Super- ficial veins, particularly in the skin, give off much heat and therefore the contained blood has a lower temperature. The hepatic veins contain the warmest blood, 39.7 C., not alone on account of the glandular activity of the liver, but also on account of the extraordinarily protected situation of the organ. The Temperature of the Tissues. The temperature of the individual tissues is the higher: (i) the more they contribute to the production of heat through the transformation of potential energy, that is, the greater their metabolic activity; (2) the more blood they contain; and (3) the more protected their situation. The muscles are the chief seat of heat-production, principally during contraction, but also during rest. The temperature of the blood in the TEMPERATURE-TOPOGRAPHY. 387 aorta is from 0.1 to 0.6 lower than that of muscle at rest. In the second place, the glands generate heat, especially during activity, par- ticularly the liver, the salivary glands, the glands of the stomach and the intestines. Berger took the temperature of different tissues in the sheep and obtained the following results : Subcutaneous connective tissue 37-35 C. Brain 40.25 C. Liver 4i.25C. Lungs 4 i . 4 o C. Rectum 40.67 C. The right heart 41.40 C. The left heart 40.90 C. In man, Becquerel and Brechet found the temperature of the subcutaneous connective tissue 2 . i C. lower than that of the adjacent muscles. The temperature of the cornea and of the aqueous humor depends in part upon the state of the iris. The smaller the pupil, the more heat must they receive from the vessels of the iris. INFLUENCES AFFECTING THE TEMPERATURE OF INDIVIDUAL ORGANS. The temperature of the individual organs is by no means constant, but there are numerous influences that at times cause it to rise and at other times cause it to fall. i. The more heat a portion of the body generates independently within itself, the higher will be its temperature. As the production of heat depends upon the metabolic changes in the organs, it follows that with the activity of the latter the degree of heat-production must keep pace. (a) The glands during secretion produce much heat, which they impart either to their secretion or to the outflowing venous blood. C. Ludwig found the temperature of the escaping saliva on irritation of the tympanico-lingual nerve 1.5 C. higher than that of the blood passing through the glandular artery to the secreting organ. The temperature of the venous blood in the secreting kidney is higher than that of the arterial blood. The secreting liver in particular produces a large amount of heat. Claude Bernard studied the temperature of the blood in the portal vein and of the blood in the hepatic veins during hunger, at the beginning of digestion and at the height of digestion, and found Temperature of portal vein 37 .8 C. ) After fasting for four days. Blood ot hepatic veins. . . . 38.4 C. j right heart during fasting 38.8 C. Temperature of portal vein . . . . 39.9 C. | A h beginning of digestion, hepatic veins 39-5 C. i Temperature of portal vein 39.7 C. ) At the height of digestion. Blood of hepatic veins. ... .41.3 C. I right heart during digestion 39.2 C. In dogs feeding or chemical or mechanical irritation of the gastric mucous membrane, and even the holding of food before the animal, brought about elevation of temperature in the stomach and the intestines. (6) The muscles produce heat in their contraction. J. Davy found the temperature of active muscle higher by 0.7. Becquerel observed in 1835, by means of the thermo-galvanometer, an increase of i C. in the temperature in the interior of a contracting muscle in man after five minutes. 388 TEMPERATURE-TOPOGRAPHY. Therefore the temperature in fast runners may rise above 40. The increase in temperature following vigorous muscular activity disappears about one and a half hours after the commencement of rest. The lower temperature of par- alyzed muscles is due only in part to the absence of muscular contractions. (c) With reference to the influence of the sensory nerves upon the temperature it should in the first place be noted whether the circu- lation is increased or diminished as a result of their stimulation, whether respiration is slowed or accelerated, and whether the muscula- ture of the body is relaxed, or is stimulated to activity through reflex influences. In the first place the temperature, in the interior of the body and the rectum, will be increased, and in the latter diminished. From this point of view the conflicting statements not rarely made can be reconciled. (d) The bodily temperature rises also (about 0.3) as the result of mental activity. The brain itself acquires a higher temperature in consequence of sensorial or sensory stimulation. (e) The parenchymatous fluids, the serous fluids and the lymph generate but little heat within themselves by reason of the slight metabolic changes that take place in them, and accordingly their tem- perature is that of their environment. The epidermoidal and horny tissues produce no heat at all, and therefore maintain their temperature from the subjacent tissues. 2. The temperature of an organ depends upon the amount of blood it contains, as well as upon the time within which the volume of blood is renewed. This is seen most distinctly in the differences in temperature between cold, pale skin, and warm, reddened skin. When Becquerel and Brechet compressed the axillary artery in a man, the temperature in the interior of the biceps muscle of the arm fell several tenths of a degree. After ligation of the crural artery and vein in dogs Landois observed the temperature decline several degrees. Long-continued elevation of the ex- tremities deprives them of blood and causes them to become colder. Attention should be called at this point to a difference between the internal and external portions of the body, which is especially emphasized by v. Lieber- meister. The external portions of the body give off more heat to the exterior than they generate within themselves. They will, therefore, be the cooler the more slowly the blood flows into them ; and the warmer the more rapid the blood- current. Acceleration of the blood-current, therefore, will cause greater uniformity in temperature between the peripheral portions and the interior of the body, while retardation of the blood-current causes greater uniformity in temperature between the peripheral portions of the body and the surrounding medium. The internal portions of the body react in exactly the opposite manner. Here active production of heat takes place, while heat-dissipation occurs almost solely through the blood-current. The temperature in these parts must, therefore, fall when the blood-current is accelerated, and the reverse. From this it follows that the greater the difference in temperature between the periphery and the interior of the body, the less is the rapidity of the circulation. 3. If the situation of an organ causes it to lose much heat by con- duction and radiation, or if other conditions bring about the same result, the temperature of the organ declines. In the first place the skin is again to be mentioned in this connection, as it must exhibit a different temperature accordingly as it is exposed to colder or warmer surroundings, or is covered or not, or is dry or moistened by perspiration (in the evaporation of which heat is lost) . The ingestion of considerable amounts of cold food and drink must cause the temperature of the stomach, and the inhala- tion of cold air must cause that of the respiratory tract down to the bronchial tree, to fall. MEASUREMENT OF THE VOLUME OF HEAT: CALORIMETRY. 389 MEASUREMENT OF THE VOLUME OF HEAT: CALORIMETRY. The calorimeter furnishes information as to the amount of heat that the body to be examined possesses or is capable of producing. The heat- unit or calory, that is the amount of kinetic energy that is capable of raising the temperature of one gram of water i C., is employed as the unit of measure. Experiment has shown that equal amounts of different bodies require unequal amounts of heat in order to attain the same temperature. For instance i kilo of water requires nine times as much heat as i kilo of iron to attain the same temperature. Wherever, therefore, different materials with equal temperatures are found, each will be endowed with different amounts of heat. The same amount of heat imparted to different bodies will, thus, also produce different temperatures in them. On the other hand, bodies naturally of different tempera- ture may possess equal amounts of heat. The amount of heat that a definite amount (as, for instance, i gram) of a body requires in order to have its tempera- ture raised a definite amount (as, for instance, i C.), is designated the specific heat of that body. The specific heat of water, which possesses the greatest of all bodies, is placed at i. Heat-capacity is the term applied to that property of bodies by means of which they are required to take up a varying amount of heat in order to maintain the same temperature. Calorimetry is employed : For the determination of the specific heat of the different organs of the body. But few observations in this connection have as yet been recorded. The specific heat of a number of animal parts, as compared with that of water as i , is as follows : Blood from man, on the average . 1.02 (?) Meat from man, on the average . . . 0.741 (it is in proportion to the num- Compact bone 0.3 ber of erythrocytes) Spongy bone.. ..0.71 Arterial blood, on the average. . 1.031 (?) Fat 0.712 Venous blood, on the average . .0.892 (?) Striated muscle 0.825 Cow's milk, on the average . . . .0.992 Defibrinated blood 0.927 The specific heat of the human body as a whole is thus only ap- proximately that of an equivalent weight of water. For the method of determining the specific heat of solid or liquid bodies works on physics should be consulted. More important is the employment of calorimetry for the estima- tion of the amount of heat that either the entire body or an individual portion is capable of producing in a definite period of time. Lavoisier and Laplace made the first calorimetric observations on animals in 1780, with the aid of the ice-calorimeter. A guinea-pig melted 13 ounces of ice in 10 hours. Crawford in 1779 and later Dulong and Despretz in 1822 employed for this purpose the water-calorimeter of Rumford after which that of Favre and Silbermann (Fig. 133) is modeled. Small animals were placed in the interior chamber (K) made of thin copper and this was immersed in a large volume of water surrounded by a poor conductor of heat. The amount of the surrounding water and its initial temperature were known. From the elevation of temperature at the termination of the experiment, which lasted several hours, the number of calories furnished could be directly estimated. The air for breathing was supplied to the animal through a special tube from a gasometer. The expired gases were examined chemically for carbon dioxid. According to Despretz, a small bitch generated 14,610 heat-units in an hour 393,000 in twenty-four hours. The taking of the temperature of the animal before and after the experiment was carelessly omitted. Assuming equal metabolic activity, a human being about seven times heavier would, on the basis of this observation, produce in the neighborhood of 2,750,000 calories in twenty-four 39 HEAT-CONDUCTION OF ANIMAL TISSUES. hours. Senator found that a dog weighing 6330 grams produced 15,370 calories, with a loss of 3.67 grams of carbon dioxid. An adult man produces at rest in twenty-four hours 2,400,000 calories, therefore 100,000 in an hour. One kilogram of body-weight produces in twenty-four hours approximately 34,000 calories, therefore 1417 in an hour. These figures increase with increase in the total metabolism and also with functional activity. The first calorimetric observations on man were made by Scharling in 1849. Leyden introduced the leg alone into the chamber of the calorimeter. This raised the temperature of 6600 grams of water i C. in an hour. If it be assumed that the total superficies of the body is about fifteen times as great as that of the leg the human body, assuming equal loss, would produce 2,376,000 calories in twenty- four hours. HEAT-CONDUCTION OF ANIMAL TISSUES. EXPANSIBILITY OF ANIMAL TISSUES BY HEAT. The heat-conduction of animal tissues is principally of importance in relation to the arrangement of the external integument and the sub- cutaneous fatty tissue. The latter especially serves as a protecting shield in warm-blooded animals living in cold water (whale, walrus, seal) and through this abstraction of heat by means of conduction from the interior of the body is practically impossible. Few investigations have been made upon this question. Greiss in 1870 determined the con- ductivity of the following tissues by noting the distance from a central source of heat introduced into the tissues at which was melted a layer of wax. He studied the stomach of sheep, the bladder of oxen, the skin of cattle, calves' feet, the hoofs of oxen, the bones of oxen, the horns of buffaloes, the antlers of deer, ivory, mother of pearl and haliotis-shell (sea-snail). He found that fibrous tissues conduct better in the direction of their fibers than at right angles to their course. The figures formed by the melting wax upon tissues spread out over a wide area were therefore generally elliptical. Landois has made observations upon a number of human tissues by determining the melting-distance of a layer of paraffin from a thin test-tube filled con- stantly with boiling water and applied intimately to tissues in layers of equal thickness, and subsequently applied on the flat and supported by threads. Desiccation was avoided, and also the effect of radiant heat. Landois was able to confirm the fact of the better conduction in the direction of the fibers. Next to bone the best conductor was found to be blood-clot; then there followed successively spleen, liver, cartilage, ten- don, muscle, elastic tissue, nails and hair, anemic skin, gastric mucous membrane, washed fibrin-fibers. The great thermic conductivity of the blood as compared with the much lower conductivity of bloodless skin is of particular interest. In this way is explained the fact that but little heat is dissipated by anemic skin, while hyperemic skin conducts and gives off a much larger amount of heat. Like all bodies the human body undergoes expansion at elevated temperatures. A man, weighing 60 kilos, will expand about 62 cu. cm. with an increase of his bodily temperature from 37 C. to 40 C. Of the different tissues, connective tissue (tendon) is expanded by heat, while elastic tissue and skin are contracted like rubber. VARIATIONS IN THE MEAN BODILY TEMPERATURE. 39 1 VARIATIONS IN THE MEAN BODILY TEMPERATURE. General Climatic and Somatic Influences. The bodily temperature remains on the whole constant within different climates. This is note- worthy if it be considered that a human being at the equator and in the polar regions is exposed to surrounding temperatures that differ from each other by more than 40 C. Further, it has been observed that when a person passes from a warm to a cold climate his temperature declines but little, but that when an individual passes from a cold to a hot region his temperature rises relatively in more considerable degree. In the temperate zone the bodily temperature in the cold winter-season is usually from o.itoo.3C. lower than on hot summer days . The elevation of a region above the level of the sea has no demonstrable influence upon the temperature. Race and sex cause no difference. Persons of vigorous constitution are believed to have a somewhat higher tempera- ture in general than debilitated, flabby, anemic persons. Influence of the General Metabolism. As the production of heat is related to the breaking up of chemical combinations, from which, in addition to the formation of water, carbon dioxid and urea finally result as the most important excrementitious products, the amount of heat generated will keep pace with the total production of those bodies formed. The increased metabolic activity that sets in after a heavy meal causes an elevation of several degrees in temperature. As the general metabol- ism is naturally much less on days of fasting than on days on which a normal amount of food is taken, it is clear that in human beings the temperature will be found to be on the average 36.6 on fasting days and 37.17 C. on ordinary days. Also Jiirgensen found in human beings on the first day of inanition a reduction in the temperature, although on the second day a transitory elevation occurred. In experiments on fasting animals it was found that the temperature declined much at first, then for a considerable time remained pretty constant, and finally in the last days declined still further. Schmidt subjected a cat to starvation, and found that up to the fifteenth day the temperature was 38.6 C.; on the six- teenth day it was 38.3, on the seventeenth, 37.64, on the eighteenth, 35.8, on the nineteenth, the day of death, 33 C. Chossat found the temperature of mammals and birds 16 C. lower on the day of death from starvation than under normal conditions. Influence of Age. The activity of the general metabolism must be in part responsible for the temperature of the body at different ages, but other influences of undetermined origin may also in part be contributory. ACE. MEAN TEMPERA- TURE AT ROOM- TEMPERATURE. NORMAL LIMITS. PLACE OF MEASUREMENT. New-born 17 4 for that of the adult, 12.31; for that of the dog' 49; for that of the rabbit, 33), then n = A^/g 2 . Age and Sex. In the earliest period of life, as well as in old age, the production of heat is less than at mature age. It is likewise so in women as compared with men. Daily Variation. The production of heat exhibits a course similar to that of the bodily temperature at different hours of the day. Bodily Functions. During waking, with physical and mental exertion, as well as during digestion (on account of the greater glandular activity) , the pro- duction of heat is greater than under the opposite conditions. RELATION OF HEAT-PRODUCTION TO THE WORK PERFORMED BY THE BODY. The potential energy supplied to the body can be transformed by the latter into heat and into kinetic energy. In the resting body almost the RELATION OF HEAT-PRODUCTION TO BODY WORK. 401 entire amount of potential energy is transformed solely into heat, for the work of the muscles of the circulatory, digestive, and respiratory organs is transformed within the body into heat, and therefore is not work transmitted outward. A man at work, however, in addition to the production of heat, transforms potential energy into work. An equiva- lent measurement will serve for the comparison of both activities, namely, i heat-unit, that is, the energy that will raise the temperature of i gram of water i C., which equals 425.5 grammeters. The following illustration will serve, first of all, to make clear the relation between heat-production and work. If a small steam-engine, in which a given amount of coal is burned, is placed within the inner chamber of a capacious calor- imeter, heat alone will be produced from the coal so long as the engine is not brought into working activity. The water in the calorimeter will indicate exactly through the elevation of its temperature the number of heat-units furnished by the burning coal. If this has been determined, the same amount of coal is burned in the steam-engine in a second experiment, but at the same time by means of a suitable device outside of the calorimeter work is performed by the engine, such as the raising of a weight. This work must naturally be furnished by the potential energy of the fuel and be transformed. If now the elevation of temperature at the end of the experiment is noted it will be found that a smaller number of heat- units have been transmitted to the water than in the first experiment, in which the engine was heated, but performed no work. Comparative experiments of this kind have demonstrated beyond doubt that in the second experiment the useful working effect is almost proportional to the heat-deficit observed. If the processes in the organism be compared with this illustration it will be seen that the resting human being generates between 2 J and 2-J million calories from the potential energy contained in the ingested food, while the amount of work performed by a laborer is estimated at 300,000 kilogram -meters. If the organism were exactly comparable with the engine, just so much less heat would have to be formed within the body as corresponds to the amount of work done. As a matter of fact, the organism naturally can transform only a lesser amount of heat from the same measure of potential energy when work is performed. One point, however, should be taken into consideration in which the laborer differs from the working engine. The laborer consumes in the same time a far larger amount of potential energy than the resting indi- vidual. A greater amount of combustion takes place in his body, and it therefore comes about that the loss through the increased combustion is not alone made good, but is even over-compensated. The laborer is, by reason of his greater muscular activity, warmer than the resting individual. The following may serve as an example of the relation in- dicated: Him in 1858 took up at rest in the calorimeter-chamber 30 grams of oxygen in an hour, and produced 155,000 calories. When subsequently he undertook in the chamber work transmitted outward, to the amount of 27,450 kilogram-meters, he consumed 132 grams of oxygen and furnished only 251,000 calories. In estimating the amount of work done only that transmitted outward as heat- equivalent is to be considered, as, for instance, the lifting of a load, the throwing of weights, the displacement of masses. Also the lifting up of the body is to be included here. In ordinary walking the overcoming of the resistance of the air and the activity of the muscles must be taken into consideration. In descending from a height an increase in heat of the body is not to be looked for, for muscular activity is required to prevent the body from falling down and from collapsing, and to avoid a too precipitate descent. 26 402 ACCOMMODATION TO VARIATIONS IN TEMPERATURE. The organism is superior to the engine in the fact that more work in proportion to heat is transformed from the same measure of potential energy. While the best gas-engine is capable of converting 10.82 per cent, of the potential energy of illuminating gas into work and the remainder into heat, the human being is capable of furnishing 35 per cent, of work in making ascents and in doing work of other character only 25.4 per cent. from the chemical transformation in its muscular tissue, Pfluger's experimental dog as much as 48.7 per cent., and an excised bit of frog's muscle even 50 per cent. Work alone, without simultaneous production of heat, can never be transformed from chem- ical potential energy in an inanimate or animate motor. ACCOMMODATION TO VARIATIONS IN TEMPERATURE. All bodies possessing great heat-conductivity, when brought in contact with the skin, appear much cooler or warmer respectively than poor conductors. The reason for this lies in the fact that they abstract more heat from the body or supply more heat to the body than the latter. Thus the water of a cold bath will always feel colder than the air at the same temperature, because it is a better conductor of heat. In the temperate zone, for example: AIR WATER At 1 8 C. feels moderately warm, Up to 18 C. appears cold, From 25 to 28 C., hot, From 18 to 29 C., cool, Above 28 C., extremely hot. From 34 to 35 C., indifferent, Above 35.5 C., warm, At 37.5 C. and above, hot. So long as the temperature of the body is higher than that of the surrounding medium, the body gives off heat, and in greater amount and more rapidly the better the conductivity of the surrounding medium. As soon, however, as the surrounding temperature becomes higher than that of the body, the latter takes up heat and in greater amount and more rapidly as the medium is a better conductor. Therefore, hot water appears to be of a higher temperature than air at the same tem- perature. A human being may remain for eight minutes in a bath at a tempera- ture of 4 5 . 5 C . , but not without risk to life . The hands tolerate immersion in water of a temperature of 5 o . 5 C . , but not of a temperature of5i.65C. At a temperature of 60 C. intense pain is felt in the integument. On the other hand, a human being may tolerate air at a temperature of 127 C. for eight minutes. Girls have remained for as long as twenty minutes in air at a temperature of 132 C. Under these circumstances the bodily temperature rises but little, namely, to 38.7 or 38.9 C. This depends upon the fact that the air, acting as a poorer conductor of heat, does not convey so much heat to the body as does water. Fur- ther, and this is the most important fact, the body exposed to hot air is capable of losing heat at its surface through abundant sweating and evaporation, and to this end the increased evaporation of water due to the increased activity of the lungs contributes. The enormous accel- eration of the heart-beat up to above 160 causes constantly renewed volumes of blood to be sent to the skin through its greatly dilated blood- vessels, for the secretion of sweat and evaporation. In the degree in ACCUMULATION OF HEAT IN THE BODY. 403 which these diminish the body becomes less capable of withstanding the surrounding heat, and thus is readily explained the fact that the human being is by far less able to withstand air rich in watery vapor than dry air at the same temperature, as heat must, under such circum- stances, accumulate within the body. Thus in the Russian steam -bath at a temperature of from 53 to 60 C. the normal rectal temperature rises to between 40.7 and 41.6 C. A human being is just able to work in an atmosphere at a temperature of 31 C. almost completely saturated with watery vapor. In water at the temperature of the body the normal bodily temperature rises i C. in one hour; about 2 C. in one and one-half hours . Gradual elevation of the temperature of the water from 38.6 to 40.2 C. caused an increase in the axil- lary temperature to 39 C. within fifteen minutes. ACCUMULATION OF HEAT IN THE BODY. As under normal conditions the constancy of the bodily temperature is the result of a constant relation between heat-production and heat- dissipation it is obvious that heat must be stored up in the body when heat-dissipation is lessened. The chief organ regulating heat-dissipation is the external integument. Contraction of the skin and its vessels diminishes heat-dissipation, while relaxation with dilatation of the ves- sels increases heat-dissipation. Accumulation of heat may, accordingly, be effected : (a) By intense and extensive cutaneous irritation, through which a transitory influence is exerted, causing contraction of the skin and its vessels. (6) Also through other forms of restriction of loss of heat through the skin, (c) Through increased activity of the vasomotor center, as a result of which contraction of all vessels, and naturally also those of the external integument, is brought about. In thi's way the elevation of temperature following transfusion of blood from an animal of the same species is to be explained direct transfusion of arterial blood from the crural artery into the adjacent vein in the same animal will suffice, as Landois was able to confirm by experiments on the carotid and the external jugular vein as well as that following venesection after a preceding decline in temperature. In both events abnormal blood-distribution takes place. In the first the venous system is abnormally overloaded, in the second abnormally empty. For the restoration of the normal distribution vigorous activity on the part of the musculature of the vessels is necessary, excited through the vaso- motor center. The marked contraction of the cutaneous vessels hereby brought about exerts an inhibitory influence on heat-dissipation and heat-accumulation thus takes place. The elevation of temperature observed after sudden abstraction of water from the body must appa- rently be explained in the same way. The inspissated blood requires less vascular space and the contracted vessels permit the escape of little heat into the skin, (d) If the circulation through the cutaneous vessels in considerable areas is retarded by mechanical means, as by occlusion of small vessels by viscous masses of stroma or coagula, which form after transfusion of blood from an animal of a different species, accumu- lation of heat takes place likewise in consequence of diminished dissipa- tion. Perhaps a number of other pyrogenic agents act in the same manner. In dogs in which both carotids and both axillary and crural 404 FEVER. arteries were ligated at one time, with or without the related veins, the temperature was observed to rise almost i C. within two hours. It is obvious that increased heat-production in the presence of normal heat-dissipation must give rise to accumulation of heat. In this category belongs the elevation of temperature following muscular and mental activity, and attending digestion. Finally, the elevation of temperature that appears several hours after a cold bath and is brought about by increased heat-production through reflex influences from the cooled skin is probably of the same character. If the temperature of the body as a whole is raised about 6 C. death results, as in the case of heat-stroke or sunstroke. At this tem- perature molecular decomposition of the tissues appears to take place. With long-continued, though less marked, elevation, distinct fatty de- generation of many tissues occurs. If animals whose temperature is raised artificially to 42 or 44 C. are subsequently placed in a cooler atmosphere, the temperature at first becomes subnormal (36 C.) and it may remain so for days. FEVER. In many ways related to the accumulation of heat largely confined within the limits of physiological phenomena fever occurs as the most common patho- logical derangement in the bodily economy and to it some reference may be made. Fever consists essentially in increased metabolism, chiefly in the muscles, together with elevation of temperature. Under these circumstances a disturbance in the regulation of the heat-balance must naturally take place, for if provision be made that with the increased heat-production also increased heat-dissipation shall take place, there can then be no elevation of temperature, or accumulation of heat. According to v. Liebermeister heat-regulation is placed upon a higher temperature- level during the febrile process. As in the state of fever the body appears to be in large measure incapacitated for mechanical activity, the transformation of this larger amount of decomposing potential energy in the body almost wholly into heat, and the failure to utilize this for mechanical activity, must moreover be especially emphasized as characteristic. Malarial intermittent fever may be considered as the prototype of fever. It is attended with severe paroxysms of fever lasting several hours in alternation with wholly afebrile periods, so that its symptoms may be readily analyzed. Among the individual phenomena of fever there are encountered: 1. Elevation of bodily temperature (to 38 or 39 C. constitutes mild, and from 39 to 41 C. and above, severe fever) . Not only the febrile patient with a burning, reddened skin (calor mordax), but also the shivering patient in a chill with an apparently cold skin may exhibit elevation of temperature. The reddened skin, however, is a good conductor, the pale skin a much poorer conductor of heat. Therefore, the former appears the warmer to the touch. 2. Increased heat-production, which had already been assumed by Lavoisier and Crawford, can be recognized indubitably by calorimetric measurement. This can be attributed only in smallest part to transformation of the increased circulatory activity into heat, but in largest part it is dependent upon heat generated in the processes of combustion. 3. Increased metabolism, to which the wasting character of fever is due. This was known to Hippocrates and Galen and was thus described by v. Barensprung in 1852 : "All so-called fever-symptoms indicate that during the febrile process tissue- consumption is abnormally increased. The increased metabolism is evidenced by augmented carbon-dioxid elimination (from 70 to 80 per cent.)- In addition to carbon-dioxid elimination there is increased absorption of oxygen, at most 20 per cent, in a patient with acute fever, while the respiratory quotient remains unchanged. According to D. Finkler the production of carbon dioxid is susceptible of greater variation than the consumption of oxygen. The state of the nutrition is an index of the size of the respiratory quotient. The increase in gaseous interchange is not the result, but the cause, of the increased bodily tem- perature. The former takes place also when the bodily temperature is reduced by FEVER. 405 a cold bath. The elimination of urea is increased between one-third and two- thirds. In dogs suffering from septic fever Naunyn observed increased elimina- tion of urea even before the temperature rose prefebrile elevation. At times, however, the urea is in part retained during the febrile process and is eliminated in large amount after the termination of the febrile attack epicritical elimination of urea. The uric acid also is increased. At the same time the urinary pigment derived from the hemoglobin may be increased twenty times and the elimination of calcium be increased seven times. The urinary water is diminished (in typhoid fever) and is excreted in greater amount during convalescence. The fact that the combustion-processes in the body of the febrile patient are exceptionally increased if he be placed in a warmer atmosphere appears especially noteworthy. During the febrile process there is also an increase in oxidation-processes under the influ- ence of colder surroundings, but the increase of combustion in warm surroundings is much greater than in cold. 4. Diminished Heat-dissipation. That in some cases febrile temperature may actually result from diminished heat-dissipation is shown, for instance, by the sudden attacks of fever that occur after catheterization or with the passage of a gall-stone through tire bile-duct. These are brought about solely through reflex irritation of the vasomotor center, which greatly interferes with heat-dissipation in consequence of contraction of the cutaneous vessels. In other forms of fever in man diminished heat-dissipation is only in part a causative factor, as the fol- lowing analysis will show: (a) The Stage of Chill, or the Cold Stage. Here the loss of heat through the pale, anemic skin, by conduction, radiation and evaporation of water, is diminished in greatest degree, but also heat-production is from one and one-half to two and one-half times greater. The rise of temperature in the febrile stage, which often is rapid and marked, alone establishes the fact that the diminished heat- dissipation is not the sole cause of the elevation of temperature. (6) In the hot stage loss of heat from the reddened, hyperemic skin is increased, but the in- creased heat-production still preponderates, v. Liebermeister estimates that a temperature-elevation of i, 2 , 3 or 4 C. corresponds with an increase in heat- production of 6 per cent., 12 per cent., 18 per cent., or 24 per cent., respectively. (c) In the sweating- stage heat-dissipation from the reddened, moist skin, and evaporation, are most pronounced, being more than two or three times the normal loss. Under these circumstances he at -production is either increased or normal or subnormal, so that under such conditions the temperature of the body likewise may become subnormal, down to 36 C. In case of fatal collapse the produc- tion has fallen to three-fourths or one-half of the normal, without simultaneous increase in heat-dissipation. Plethysmographic examinations of the vessels of the arm in febrile patients have shown, in accordance with the temperature- variations during the febrile process, that the blood-vessels begin to contract before any elevation of tem- perature is evident. With the progress of the contraction the temperature then rises, and both reach their maximum at the same time. The decline in tempera- ture is subsequently preceded by dilatation of the vessels, and with marked dilata- tion of the vessels the temperature again falls to the normal level. 5. Deranged Heat-regulation. High surrounding temperature may increase that of the febrile patient more than that of a non-febrile individual. The reduc- tion in heat-production that permits normal animals to maintain their normal temperature in warm surroundings is far less during fever. Among the accessory phenomena of fever the following are especially note- worthy: Increase in the intensity and number of the heart-beats, and respiration in adults to 40, in children to 60 in the minute. Both are compensatory phenomena of the elevated temperature. There are, further, diminished digestive activity and intestinal movement, derangement of cerebral activity, of the secretions, of muscu- lar activity, interference with elimination, as for instance of water, or of admin- istered potassium iodid, through the urine. Febrile pyrexia is by some con- sidered as having a curative influence on the body, it being reasoned that the body is cleansed and purified by the heat of the fever. In the presence of high fever molecular degeneration of the tissues has often been found. With respect to the blood-corpuscles during fever reference may be made to p. 50, i, to the amount of carbon dioxid in the blood on p. 81, to the vascular tension on p. 142, to the saliva on p. 339, to the digestion on p. 341 D. The utiliza- tion of the food throughout the entire tract has not been found interfered with in marked degree. In experiments on animals Krehl and Mathes found an increase of 10 per 406 ARTIFICIAL ELEVATION OF THE BODILY TEMPERATURE. cent, in heat-production in conjunction with elevation of temperature, and diminu- tion in heat-dissipation. At the height of the fever heat-production was likewise increased, while heat-dissipation was increased only when heat-production was considerable. With decline of temperature heat-production is generally diminished while heat-dissipation varies. According to Filehne, Hildebrand, Richter, Stern, and others, antipyretics act by restoring heat-regulation to a lower level. Quinin reduces temperature by limiting heat-production. Toxic doses of metallic salts act similarly, diminished carbon-dioxid formation being at the same time demonstrable. According to others the influence of antipyretics is exerted principally upon the increase of heat-dissipation through the dilatation of the vessels, while heat-production is but little diminished about 15 per cent. The course of heat-production in infected cold-blooded animals follows that in febrile warm-blooded animals. It rises at the height of the disease and falls during collapse. Even in plants injured bulbs Pfeffer observed phenomena analogous to fever. ARTIFICIAL ELEVATION OF THE BODILY TEMPERATURE. Elevation of the bodily temperature, in addition to causing disturb- ances of the general condition, influences, first of all, consciousness, so that mental confusion, vertigo, insomnia and loss of consciousness occur. The functions of the medulla oblongata and the spinal cord are affected only later. If mammals are kept constantly in air at a temperature of 40 C. escape of heat from the body ceases, and accordingly accumulation of the heat produced must take place. At first the bodily temperature declines somewhat for a short time, but later a distinct elevation sets in. Respiration and pulse are accelerated and the latter becomes weaker and irregular. Absorption of oxygen and elimination of carbon dioxid diminish in the course of from six to eight hours, and death takes place amid signs of great exhaustion, convulsions, salivation and loss of con- sciousness, even when the temperature of the body is not increased more than 4 or at most 6 C. Death is due not to the rigidity of the muscles, as the coagulation of their myosin does not take place in mammals at a temperature below 49 or 50 C., in birds at a temperature of 53 C., in frogs at a temperature of 40 C., but probably to a derangement of the heat-regulating functions of the nerves. If mammals are exposed suddenly to air of a high temperature, 100 C., death takes place amid similar phenomena, but much more rapidly in fifteen or twenty minutes. The temperature of the body rises only 4 or 5 C. under such circumstances. Under like conditions a loss of i gram in body- weight is observed in rabbits within a minute. Birds tolerate the high temperature somewhat better, dying only after the temperature of their blood reaches 48 or 50 C. Man also is capable of surviving for a short time in air having a temperature between 100 and 132, although the greatest danger to life sets in in the course of ten or fifteen minutes. At the same time the skin becomes burning red, copious sweating takes place, and the cutaneous veins are greatly distended and of a brighter red appearance. Pulse and respiration are greatly accelerated. Severe headache, vertigo, exhaustion and failure of sensor} 7 activity are in- dicative of great danger. At the same time the temperature taken in the rectum will have risen but i or 2 C. According to the observations of C. A. Koch, v. Voit and Simanowsky, artificial elevation of tempera- ture in man and animals is not followed by increased proteid metabolism, whence it is to be concluded that the increased proteid metabolism EMPLOYMENT OF HEAT. 407 attending the febrile process cannot be dependent upon the elevation of temperature, but must be brought about by the inadequate nutritive state of the tissues, or by bacterial poisons. Fever may also endanger life through elevation of the bodily temperature. If the temperature re- mains at 42.5 C. for a considerable time death is unavoidable. If the artificial elevation of temperature is not increased to the point of causing death, beginning in from thirty-six to forty-eight hours fatty infiltration and degeneration will take place in the liver, the heart, the kidneys and the muscles. In cold-blooded animals the temperature can be raised from 6 to 10 C. within a short time, by exposure to hot water as well as to hot air. As the heart of the frog ceases to beat at a temperature of 40, and as the muscles in the interior of the body begin to become rigid at the same temperature, the maximum tempera- ture for the continuance of Hfe is in this animal considerably lower. Actual death is preceded by a condition of apparent death, from which resuscitation is possible. Insects live in the desert at a temperature of 64 R. and arctisca and anguillulae die in water at a temperature of 45, while in a dry medium they can be heated to a temperature of 70, and rotifers, after careful desiccation, can be heated to 125 C. Most juicy plants die after exposure for half an hour to air at a temperature of 52 C. or to water at a temperature of 46 C. Desiccated seeds (oats) may retain their germinating activity after exposure for a considerable time to air at a temperature of 120 C. Lowly organized plants, such as the algse, can live in warm springs at temperatures up to 60 C. Some bacteria tolerate the boiling temperature. EMPLOYMENT OF HEAT. Brief and not intense heat applied to the surface of the body causes at first a transitory, slight reduction in the bodily temperature, partly because the pro- duction of heat is thereby diminished through reflex influences, partly because more heat is given off in consequence of dilatation of the cutaneous vessels and expansion of the skin. Baths at a temperature above that of the blood cause at once elevation of the bodily temperature. Following the bath a slight reduction in temperature takes place after a time. Apart from the changes in bodily tem- perature brought about by changes in circulation and in respiration, Oppenheimer estimates the elevation of temperature, t, brought about by a bath of 400 liters (kilos) at a temperature of 40 C. and of half an hour's duration (the time required to warm the body thoroughly), in a man weighing 75 kilos, with a bodily tem- perature of 37 C., assuming equal heat-capacity for the body and the water of the bath : (400 + 75) t = 400.40 + 75,37; therefore t = * !/ _ = 39.5. The temperature of the body, thus, rises from 37 to 39.5 C., an increase of 2.5 C., representing 187,500 heat-units. General application of heat to the entire body is indicated when the bodily temperature has fallen extremely low, or when danger is threatened thereby, as in the algid stage of cholera, and in the case of a premature human fetus. General supply of heat is effected by means of warm baths, packs (beds) , vapors, insolation, and copious hot drinks. Heat is applied locally by means of hot compresses, partial baths, placing of a part in hot earth or sand, introduction of a part into the body of a recently killed animal (animal bath) , introduction of injured parts into receptacles containing heated air. After removal of the heating agent, the greater amount of heat-dissipation caused by the dilatation of the vessels is to be taken into consideration. POST-MORTEM ELEVATION OF TEMPERATURE. R. Heidenhain found as a constant phenomenon in dogs that were killed that a transitory elevation of temperature took place before the cooling of the cadaver set in, and this slightly exceeded the normal temperature of the body. Similar, and in part remarkable, elevations of temperature had been observed 408 THE INFLUENCE OF COLD UPON THE BODY. previously in human bodies immediately after death, particularly when this re- sulted from violent muscular spasm. Thus, for instance, Wunderlich found a temperature of 45.375 C. in a body fifty-seven minutes after death from tetanus. The causes of post-mortem elevation of temperature reside : 1. In a transitory increase in heat-production after death, and especially through the conversion of the viscid contents of the muscles (myosin) into the solid form of coagulation (muscular rigidity). The muscle in the process of be- coming rigid produces heat. All causes that excite rapid and intense muscular rigidity including transitory spasm therefore favor post-mortem elevation of temperature. Rapid coagulation of the blood must also contribute to the produc- tion of heat. 2. Further, a series of chemical processes take place in the interior of the body soon after death that produce heat. When Valentin placed dead rabbits in a chamber at the temperature of the body, and in which loss of heat from the body was impossible, the internal temperature of the body rose constantly. The processes that thus give rise to the production of heat after death take place more rapidly in the first hour than in the second. The higher, further, the bodily temperature at the moment of death, the more considerable will be the post-mortem generation of heat. 3. Diminished heat-dissipation after death is a third cause. As the circulation is abolished within a few minutes, but little heat is given off from the cutaneous surface of the cadaver, because in order that rapid loss of heat should take place constantly renewed filling of the cutaneous vessels with warm blood is necessary. THE INFLUENCE OF COLD UPON THE BODY. Transitory slight cooling of the external integument causes either no change in the bodily temperature or a slight elevation. The latter is dependent upon the fact that both through reflex influences a more rapid molecular transformation for purposes of heat-production is stimulated, as well as through contraction of the small cutaneous vessels and the skin itself heat-dissipation is diminished. The long-continued action of more intense cold, however, causes reduction in temperature, particularly through conduction, in spite of increased heat-production at the same time. Thus, after cold baths the temperature may be 34 or 32 C., and even as low as 30 C. Cold baths at a temperature below 25 cause the cutaneous temperature to fall as low as 19. Within the interior of the body the temperature, after remaining stationary for a moment, declines in proportion to the intensity of the cooling. If the cooling be continued the body is placed in the condition of that of a cold-blooded animal. As an after-effect of marked abstraction of heat, it is found that the bodily temperature remains for some time lower than it had been before primary after- effect. It was, for example, only 22 C. in the rectum at the end of an hour. The designation secondary after-effect is applied to the elevation of temperature that takes place after the primary after-effect has been neutralized. This begins after cold baths at the end of from five to eight hours, and reaches in the rectum about 0.2 C. In an analogous manner Hoppe-Seyler observed in the course of a short time a decline in the bodily temperature after the action of heat upon the body. Catching Cold. If the body of a rabbit is suddenly cooled after exposure to a surrounding temperature of 35" C. transitory diarrhea occurs at times, in addition to shivering. In the course of one or two days the temperature rises 1.5 C. and albuminuria sets in. Kidneys, liver, lungs, heart, nerve-sheaths, exhibit micro- scopic traces of interstitial inflammation; the dilated arteries, particularly in the liver and the lungs, contain thrombi, and the adjacent veins migrated leukocytes. In pregnant animals even the fetus exhibited the same conditions. In explanation of the phenomenon the question may be discussed whether increased destruction of the cellular elements does not take place in the greatly cooled blood. Freezing. As a result of the long-continued action of high degrees of cold upon the skin , the musculature of the skin and its vessels contracts at first , in con- sequence of the stimulating influence of the cold, and pallor of the integument develops. If the action be maintained, paralysis of the walls of the vessels takes place, and the skin becomes reddened, with dilatation of the vessels. As the pas- sage of fluids through the capillaries is seriously embarrassed in consequence of the action of the cold, stagnation of the blood results. This soon makes itself manifest as livid discoloration, as the oxygen is almost consumed in the small ARTIFICIAL REDUCTION OF BODILY TEMPERATURE IN ANIMALS. 409 vessels in consequence of the slowness of the current. Thus the circulation at the periphery is slowed. If the intense effect of the freezing be continued the movement of blood at the periphery ceases entirely and principally in the thinnest parts, namely the ears, the nose, the toes and the fingers. The functions of the sensory nerves become impaired, and numbness and anesthesia develop. Later there may be even complete freezing throughout. If the peripheral parts become anemic, the internal organs naturally become hyperemic and the heart is distended with blood. As the retardation of the circulation must naturally be transmitted from the surface of the body to the other circulatory areas, increased venosity of the blood develops in consequence of diminished circulation through the lungs, notwith- standing the larger amount of oxygen in the cold, dense air, and as a result the activity of the nerve-centers is affected. Great disinclination to movement, a distressing feeling of fatigue, a peculiar irresistible tendency to sleep, an inability to think logically, uncertainty in sensorial activity, and finally complete loss of consciousness are the symptoms of this condition. At a temperature of 0.56 C. the blood freezes, while the fluids of the superficial portions of the body become rigid somewhat earlier. The protoplasm, as, for instance, of the muscles, may be cooled on careful^ experimentation down to a temperature of 18 C. without becoming solid. In making attempts at resuscitation or at thawing, all bending or breaking movements of the rigid parts is to be avoided, in order that the crystals of ice do not perforate the tissues. Further, too rapid heating is to be avoided, as hereby sudden expansion of the tissues might be brought about, and give rise to their molecular destruction. Simple rubbing with snow in order if possible to set the blood gradually in motion from the parts that are not frozen toward those that are rigid, with gradual warming, will yield the best results. Often complete freezing is followed by partial death of the affected part. ARTIFICIAL REDUCTION OF THE BODILY TEMPERATURE IN ANIMALS. In consequence of reduction of the temperature of the body the activity of the most highly developed nerve-centers (cerebrum) is diminished first and only later that of the medulla oblongata. If "the functions of the latter are beyond restoration death must result. Artificial reduction of the temperature in warm-blooded animals by exposure to a cold atmosphere, or to cold-mixtures, is followed by a series of characteristic phenomena. If the temperature of the animals rabbits is lowered to 18 C. rectal temperature they are overcome by great prostration, without abolition, however, of voluntary and reflex movements, although these are lost at a temperature of 17 C. The pulse is reduced in frequency from 100 or 150 to 20 beats in a minute, and at the same time the blood-pressure falls to a few millimeters of mercury. Respirations are infrequent and superficial, and breathing, therefore, becomes inadequate (at 25 C., in rabbits). Asphyxia is no longer capable of exciting convulsions ; the secretion of urine ceases ; and the liver exhibits excessive hyperemia. In this condition the animal may remain for twelve hours; then, after the muscles and the nerves exhibit signs of paralysis, coagulation of the blood has taken place fol- lowing the destruction of large numbers of blood-corpuscles, and the eye-ground has become pale, death takes place amid symptoms of paralysis of the heart, convulsions and asphyxia. If left to itself, an animal whose temperature has been reduced to 1 8 C. is incapable of recovery when the surrounding temperature is the same. If, however, artificial respiration is practised the bodily tem- perature rises 10. If in conjunction with the latter, heat is in addition supplied from without, the animals recover completely, even when they have been apparently dead for about forty minutes. Walther was 4IO ARTIFICIAL REDUCTION OF BODILY TEMPERATURE IN ANIMALS. in this way able to resuscitate full-grown animals whose temperature had been reduced to 9 C. and Howarth young animals even when the temperature had been reduced to 5 C. Mammals born blind and birds born without feathers, if left to themselves, suffer reduction in temperature more rapidly than others. Morphin, and in still greater degree alcohol, accelerate the reduction in the temperature of mam- mals, the gaseous interchange at the same time falling considerably, and for this reason drunken persons are more readily exposed to the danger of death from freezing. Knoll lowered the temperature of rabbits by means of intravenous infusion of an ice-cold indifferent solution of sodium chlorid. He found reduction in pulse-frequency, prolonged systole, paralysis of the cardiac branches of the vagus, primary increase -and secondary reduction in blood-pressure, accelerated, super- ficial breathing and later diminished frequency of breathing. Cl. Bernard made the remarkable discovery that the muscles of animals whose temperature had been reduced maintain their irritability for a longer time, with respect to direct stimuli, as well as to stimulation through the nerve. He found the same condition when the animals were asphyxiated through deficiency of oxygen. Artificial cold-bloodedness, that is, a condition in which the temperature of warm- blooded animals is reduced, with preservation of the irritability of muscles and nerves, can be developed in warm-blooded animals also by division of the cervical cord while artificial respiration is maintained, and further by application of a cool solution of sodium chlorid to the peritoneum. Hibernation, which is due essentially to the lowering of the temperature of the animals, exhibits a series of analogous phenomena. Valentin found that the marmot begins to be only half awake when the bodily temperature reaches 28 C. ; at a temperature of 18 C. it is soporose; at 6 it exhibits shallow and at 1 6 C. deep sleep. At the same time the heart-beats fall to 8 or 10 in a minute, with reduction in the blood-pressure. The respirations and the movements of the bladder and the intestine cease entirely, and only the cardio-pneumatic movement maintains the slight diffusion of gases in the lungs. The temperature does not fall as low as o, but the animals awaken before the temperature has fallen to this level. At a temperature of o C. no further dissociation of the oxy hemo- globin would take place. Hibernating animals, indifferently whether in the waking or in the sleeping state, may, however, survive an artificial reduction of temperature down to 1 C. and recover spontaneously. Hibernating animals, therefore, submit to a greater reduction of temperature than other mammals. Under such circumstances, they yield up their heat rapidly and they are able to renew their heat with rapidity even spontaneously. Newborn mammals more closely resemble hibernating animals in this respect than do adult animals. The animals can be awakened from their winter's sleep by sensory stimulation and in- creasing temperature through the agency of the nerve-centers. In cold-blooded animals exposed to great cold the temperature can be reduced almost to the freezing-point tenches can be frozen into ice. In the state of cold their metabolism is greatly lowered and the animals are apparently dead, although they recover rapidly when exposed to warmer surroundings. Under favorable con- ditions animals frozen into a mass of ice may be resuscitated the frog. If, for example, however, the fluids throughout the body have been frozen into ice, the animals will die, for the reason that with the formation of ice in the tissues, the gases are expelled in the form of bubbles and the salts separate in the form of crystals. The germs and ova of lower forms of animal life, as, for instance, the eggs of insects, survive long-continued, severe cold. A moderate degree of cold only retards their development. Snakes tolerate an external temperature of 25, frogs a temperature of 28, myriapods and infusoria a temperature of 50, snails for days a temperature of 120. Germs, grains of seed and spores of fungi exposed to a temperature of 200 are capable of germinating after EMPLOYMENT OF COLD. 4 H being again warmed, and also the seeds of wheat, oats, peas, etc., exposed for four or five days to a temperature of 192 C. The application of a coat of varnish to the skin gives rise to a series of condi- tions similar to those due to reduction in temperature. The varnished skin readily gives off heat outward through radiation, particularly as the blood-vessels of the skin are enormously dilated. Therefore the temperature of the animals falls greatly and some even die. If the reduction in temperature be prevented by applications of heat and of external coverings the animals survive. The blood of such animals as die contains no toxic substances and no retained excremen- titious matters that might have caused death, for other animals injected with such blood remain healthy. In human beings varnishing of the skin appears to have no injurious effect. EMPLOYMENT OF COLD. Applications of cold to a large part of the surface of the body may be made from the following points of view : (a) By means of cold baths or packs of considerable duration to remove large amounts of heat from the surface of the body when the temperature in the presence of fever has attained a dangerous elevation. This effect can be produced in a most lasting manner if the temperature of the bath is at first moderate and is gradually reduced, because the skin is rendered anemic and becomes contracted in consequence of low degrees of temperature, so that a marked obstacle to the dissipation of heat at once arises. Also, the gradually cooled bath is borne for a considerable time. The addition of stimulating substances, as, for instance, salt, which effects dilatation of the cutaneous vessels, favors heat-dissipation, chiefly because the salt-water acts as a better conductor of heat. The reduction in temperature is favored by simultaneous administration of alcohol internally. Also, evaporation of water from the skin, through spraying with aqueous vapor, is adapted for the reduction of the bodily temperature. (6) Local external reduction of temperature, as by means of an ice-bag, serves in the first place to cause contraction of the vessels and of the tissues, as in case of inflammation, with simultaneous local abstraction of heat. Whether, under such circumstances, the heat-generating molecular disintegration of potential energy is retarded locally or not is as yet undetermined. (c) Local abstraction of heat through the rapid evaporation of volatile sub- stances, such as ether and carbon disulphid, causes anesthesia of sensory nerves. The introduction of media of low temperature into the interior of the body, such as the inhalation of cold air, the ingestion of cold drinks, cold injections into the intestine, the bladder or the genital tract, in part acts locally and in part may cause general abstraction of heat if the action be long continued and intense. In connection with the action of cold it should be borne in mind that the contraction of the vessels and the collapse of the tissues after cessation of the effect are usually followed by increased fulness and turgescence. THE TEMPERATURE OF INFLAMED PARTS. Heat is considered one of the fundamental phenomena of inflammation, in conjunction with redness, swelling and pain. Nevertheless, the apparent increase in the temperature of inflamed parts is by no means dependent upon increase in the temperature above that of the blood, a condition that has never been observed. In consequence of the dilatation of vessels, which causes redness, and the increased amount of blood flowing through the inflamed parts, as well as through tumefaction of the tissues with well-conducting fluid, the external portions of the body, such as the skin, are usually of a higher temperature than normal, and at the same time they more readily give off heat through conduction. Whether or not increased heat-production takes place in the inflammatory focus itself, perhaps in accordance with the character of the inflammatory process, in consequence of accelerated molecular disintegration, has not as yet been de- termined. HISTORICAL. COMPARATIVE. Hippocrates born 460 B. C. considered the indigenous heat as the cause of life. According to Aristotle the heart prepares heat within itself and distributes it to all parts of the body, together with the blood. This doctrine, which is pre- 412 HISTORICAL. COMPARATIVE. sented in a similar manner also in the writings of Hippocrates and Galen, was for a long time the dominating one, and is found last in the writings of Cartesius and Bartholinus (1667, "Flammula cordis"). The iatromechanical school attributed the heat to the friction of the blood in the walls of the vessels. The iatrochemical school, on the other hand, looked for the source of heat in fermentative processes taking place in the blood through the entrance of absorbed articles of food. Lavoisier was the first, in 1777, to make the combustion of carbon in the lungs the source of heat. After the invention of the thermometer by Galileo, Sanctorius in 1626 made the first thermometric observations on the sick, while the first calorimetric observations were made by Lavoisier and Laplace in 1780. Compara- tive observations have already been recorded on p. 382, and also with respect to hibernation on p. 410. PHYSIOLOGY OF METABOLISM. SCOPE OF METABOLISM. By metabolism is understood the phenomenon common to all living organisms, sharply differentiating the organized from the unorganized, and consisting in the power of incorporating into their own tissues the substances obtained from food (in animals by means of digestion) and of forming them into component parts of their own animate bodies. This division of metabolism is designated assimilation. More- over, out of these assimilated substances, which constitute a reservoir of potential energy, the organism is, by means of transformation-processes, able to develop activities in the form of kinetic energy, which are mani- fested most strikingly among the higher animals as muscular work and heat. The resulting transformation of tissue-constituents, which ter- minates in the formation of excrementitious substances, is thus an in- direct object in the study of metabolism. Normal metabolism requires, accordingly, food-material suitable both qualitatively and quantitatively; a storing up within the body, in proportion to the consumption ; a regulated chemical transformation of the tissues ; and the preparation of the waste-products to be thrown off by the organs of excretion. SYNOPSIS OF THE MOST IMPORTANT SUBSTANCES USED AS FOOD. WATER. EXAMINATION OF DRINKING-WATER. When it is considered that the body contains in all of its tissues about 58.5 per cent, of water, that water is constantly being thrown off with the urine and the feces, as well as by the skin and the lungs, and that in the processes of digestion and absorption most substances must be dissolved in water, and likewise that numerous waste-products, especially in the urine, must leave the body in aqueous solution, the importance of a constant supply and continual renewal of water will be at once obvious. Hoppe-Seyler epitomized admirably the importance of water to life in the following words: "All organisms live in water, and indeed in running water," a saying that deserves a place by the side of the old one of "Corpora non agunt nisi fluida." Leaving out of consideration its presence as a constituent of fluid food, water is used as a drink in different forms: (i) As rain-water (in some countries, where it is collected in suitable reservoirs, cisterns, etc.) , which most closely approximates distilled (chemically pure) water, although it, nevertheless, always contains small amounts of carbon dioxid, ammonia, nitrous and nitric acids. (2) As well-water or spring-water, which is ordinarily rich in mineral matter, it results from atmos- pheric precipitations, which filter through the layers of earth rich in carbon dioxid, and with the aid of the absorbed carbon dioxid it is capable of dissolving out the alkalies, the alkaline earths and metals. These substances enter into solution as bicarbonates, for instance calcium carbonate and ferric carbonate. The water is either drawn from the wells by mechanical appliances or it gushes from the 414 EXAMINATION OF DRINKING-WATER. surface of the earth in certain localities in the form of springs. (3) The running water of streams, rivers and brooks is generally much poorer in mineral matter than that of wells or springs. Flowing on the surface spring- water soon gives off much of its carbon dioxid. As the solution of many minerals is possible only in the presence of carbon dioxid, insoluble precipitates of these substances must result. The water of wells and springs is poor in oxygen, and on the other hand rich in carbon dioxid. The latter gives it its refreshing and stimulating properties. For the same reason a generous vegetable life is possible about springs, while on the other hand the existence in spring-water and well-water of animal organisms requiring oxygen is extremely limited. Freely running water, however, absorbs oxygen from the air, while giving off carbon dioxid, and thus supplies the necessary conditions for existence to fishes and other aquatic animals. River- water contains about from ^ to oV f its volume of absorbed gases, which may be driven off by boiling or freezing. The water from wells and springs chiefly is used for drinking-purposes. River- water (with which, unfortunately, some large cities must yet content themselves) demands first a careful removal of the clay and other accidental impurities sus- pended in it. It may be cleared and purified by means of large filter-beds made of thick layers of sand mixed with charcoal. On a small scale the commercial charcoal-filter can be used with advantage to clarify the water, the charcoal being in addition disinfectant. In this connection it is a noteworthy fact that alum in a dilution of o.oooi per cent, is able to clarify turbid water. EXAMINATION OF DRINKING-WATER. Drinking-water (even when viewed in thick layers) should be perfectly color- less and clear, also without odor, which is best perceived by heating to 50 C., with or without addition of sodium hydroxid. Moreover, it should not be too hard, that is, not unduly rich in salts of calcium and magnesium. By the term degree of hardness is designated the content of compounds of cal- cium and magnesium in 100,000 parts of water. A water of 20 degrees of hardness contains, therefore, in 100,000 parts, 20 parts of calcium (calcium oxid) in com- bination with carbon dioxid, sulphuric and hydrochloric acids (the small amounts of magnesium need not be taken into consideration) . A good drinking-water should not greatly exceed 20 degrees of hardness. To determine the degree of hardness a titrated soap-solution may be used. This is shaken with the water to be exam- ined, and the later that foam appears the harder is the water. The degree of hardness exhibited by unheated water is designated its total hardness; that of heated water its permanent hardness. By means of boiling, the calcium carbonate principally is precipitated, as a result of the escape of the carbon dioxid. It is on this account that boiled water becomes softer. Turbidity of the water following the addition of hydrochloric acid and barium- chlorid solution indicates the presence of sulphuric acid, usually in combination with calcium. As chlorin (always in combination with a metal) appears only in small quanti- ties in pure spring-water, and as its presence in large amounts (apart from saline springs, the vicinity of the sea, or factory-sewers) generally indicates a commu- nication with water-closets or manure-heaps, the estimation of this is of especial interest. For purposes of demonstration, 20 cu. cm. of water are mixed with a few drops of nitric acid, and silver nitrate is added; a precipitate of silver chlorid results. For quantitative estimation by titration there are necessary a solution A of 17 grams of crystallized silver nitrate in i liter of water (i cu. cm. of this solution precipitates 3.55 mgm. of chlorin as silver chlorid) ; and also a cold saturated solution B of neutral potassium chromate. In testing, 50 cu. cm. of the water to be examined are placed in a beaker, 2 or 3 drops of the solution B are added, and then from a buret solution A is permitted to flow drop by drop until the precipitate, at first white, remains red, even after stirring. If the number of cubic centimeters of A used be multiplied by 7.1, the amount of chlorin con- tained in 100,000 parts of water will be obtained. Example: if 50 cu. cm. required 2.9 cu. cm. of silver-solution, then 100,000 parts of water contain 2.9 X 7-* = 20.59 parts of chlorin. In good drinking-water the chlorin should not exceed 15 mgm. in i liter. If 50 cu. cm. of water are acidulated with a little hydrochloric acid, then ammonia added in excess, and to this a solution of ammonium oxalate, the white precipitate obtained is calcium oxalate. According as the resulting turbidity is only slightly cloudy or markedly milky it is known whether the water is soft EXAMINATION OF DRIXKIXG-WATER. 415 (poor in calcium) or hard (rich in calcium). After this calcium-precipitate has settled, the clear fluid is poured off and mixed with a solution of sodium phos- phate and a little ammonia; the crystalline precipitate that now forms indicates the presence of magnesia. The feebler the reactions for sulphuric acid, chlorin, calcium and magnesium, the better is the water. Good drinking-water, should, moreover, contain only traces of nitrates, nitrites and ammonium-compounds, as their presence points to organic substances containing nitrogen in a state of decomposition. Nitricacid is indicated when 100 cu. cm. of water are acidulated with two or three drops of concentrated sulphuric acid, some bits of zinc are added and then a solu- tion of iodin, zinc and starch, and a blue tint appears. The following test is exceed- ingly sensitive : some fragments of brucin sulphate along with a drop of the water to be examined are to be placed in a watch-glass; then a few drops of concentrated sulphuric acid are added. A rose-red color appears. Diphenylamin sulphate mixed with a few drops of concentrated sulphuric acid yields in the presence of nitrates, even when in great dilution, a blue color. This test is, therefore, recom- mended for the demonstration of well-water in milk. Demonstration of^nitrous acid: To 100 cu. cm. of water a few drops of pure concentrated sulphuric acid and a solution of zinc iodid and starch are added: a blue color appears. In addition naphthionic acid and pure /3-naphthol, thor- oughly mixed in a mortar, are recommended as a reagent. To 10 cu. cm. of the fluid to be examined for nitrites two drops of a concentrated solution of hydro- chloric acid and as much of the mixture mentioned as can be taken up on the point of a knife are added and the whole is thoroughly shaken. If ammonia is added in a layer on top of this mixture a red ring appears. This test has a sensi- tiveness of i : 100 millions. Ammonium-compounds in considerable amount render the water suspicious. To 150 cu. cm. of water 0.5 cu. cm. of solution of sodium hydrate and i.o cu. cm. of solution of sodium carbonate are added and the precipitate is allowed to settle. Of the supernatant clear fluid a column 15 cm. high is introduced into a narrow graduated cylinder and mixed with Nessler's reagent (a solution of mercuric iodid and potassium iodid in an excess of potassium hydroxid) : Traces of ammo- nia in water thus yield a color between yellow and red, large amounts a brown precipitate of mercuric -ammonium iodid. The contamination of water by decomposed animal substances will be recog- nized by the amount of contained nitrogen. In most cases it is sufficient to determine the amount of nitric acid. For this two solutions are necessary: A, containing 1.871 gin. of potassium nitrate to a liter of water; i cu. cm. of this contains i gram of nitric acid; B, a dilute solution of indigo; i part of pulverized indigotin is slowly added with stirring to 6 parts of fuming sulphuric acid; the mixture is allowed to settle, the blue liquid is poured into 40 times its amount of distilled water and then filtered. Finally, the fluid is diluted with distilled water until it begins to be transparent in layers of from 12 to 15 mm. thick. To test the efficiency of B, i cu. cm. of A is mixed with 24 cu. cm. of water, some table-salt and 50 cu. cm. of concentrated sulphuric acid are added, and so much of B is now allowed to flow from a buret until a faint green tint appears. The number of cubic centimeters of B used corresponds to i mgm. of nitric acid. Twenty-five cubic centimeters of the water to be examined are mixed with 50 cu. cm. of concentrated sulphuric acid and titrated with B until the green color appears. This titration must, however, be repeated, and in the second observa- tion the number of cubic centimeters of indigo-solution be permitted to flow in a stream; a somewhat larger amount of fluid may be required to produce the green color. The number of cubic centimeters of solution B thus used (in proportion to the previously ascertained strength) indicates the amount of nitric acid present in 25 cu. cm. of water. In well-water as much as 10 mgm. nitric acid is found in the liter. Hydrogen sulphid is recognized, apart from its odor, through the brown color imparted to a piece of filter-paper that has been saturated in an alkaline solution of lead, and is held over the water boiling in a flask. If hydrogen sulphid is present in combination in the water, some sodium hydroxid and a dilute solution of sodium nitro-prussid are added; a reddish- violet color appearing It is of the greatest significance with respect to the excellence of drinking- water that it should be free from putrefying or decomposing organic matter. _ The latter, in conjunction with the lower organisms always to be found in it, when ingested with drinking-water, expose the body to serious dangers, as a number of infectious diseases,, especially cholera and typhoid fever, can be spread 416 EXAMINATION OF DRINKING-WATER. in this manner. The latter is especially the case if the wells in use lie near water- closets and manure-heaps, so that the products of decomposition can filter through into the reservoir for the water. Qualitative Demonstration. (i) A fairly large amount of water is evaporated in a porcelain dish to dryness, and is then subjected to greater heat. If large amounts of organic matter are present a discoloration between brown and black takes place. If the matters contain nitrogen the odor of 'burning hair appears at the same time. Good water, so treated, yields but a faint brown color. Micro- scopic examination may also be made to determine the presence of microorganisms in water. About i cu. cm. of water is allowed to evaporate upon a slide having an up-turned edge and kept in a place free from dust, and the dry spot is examined. (2) A solution of gold-pota % ssium chlorid added to water produces, after stand- ing for a long time, a black muddy precipitate. (3) A solution of potassium per- manganate added to the water placed under cover is gradually decolorized, with the formation of a brown muddy deposit. The precipitates from 2 and 3 are the more abundant the greater the amount of organic substances present in the drinking-water. Quantitatively the amount of organic substances is determined, according to Kubel, as follows. Two solutions are required: A, containing 0.63 gram of pure crystalline oxalic acid in i liter of distilled water; B, containing 0.33 gram of potassium permanganate in i liter of purest distilled water. For the determination of the efficiency of the latter 100 cu. cm. of distilled water are placed in a wide-necked bottle of 300 cu. cm. capacity, together with 5 cu. cm. of dilute sulphuric acid (i volume of acid to 3 volumes of water) and heated to boiling. Into this from 3 to 4 cu. cm. of solution B are allowed to flow from a buret provided with a glass stop-cock. The mixture is boiled for ten minutes, the heat is then removed and 10 cu. cm. of solution A are added. Finally, the fluid, which has become colorless, is mixed with solution B until a faint red tint appears. The number of cubic centimeters used corresponds to 6.3 mgm. of oxalic acid, which are present in the 10 cu. cm. of solution A, and contains exactly 3.16 mgm. of potassium permanganate, or 0.8 mgm. of oxygen available for oxidation, which is necessary for the transformation of the 6.3 mgm. of oxalic acid into carbon dioxid. In order to test a given water for the amount of organic matter present, 100 cu. cm. of the sample are placed in a flask of 300 cu. cm. capacity, 5 cu. cm. of dilute sulphuric acid are added and so much of solution B that the fluid becomes an intense red and remains so even when heated. After five minutes' boiling, 10 cu. cm. of solution A are added. The fluid, thus made colorless, is then titrated with solution B until a faint red tint appears. For purposes of calculation as many cubic centimeters of solution B as are necessary for the oxidation of 10 cu. cm. of solution A are subtracted from the total number of cubic centimeters of solution B used in the experiment. The difference in cubic centimeters is multiplied by 3.16 : x if the proportion of potas- sium permanganate, by 0.8 :x if the proportion of oxygen, necessary for the oxidation of the organic substances present in 100,000 parts of water is desired (x represents the number of cubic centimeters of solution B that corresponds to 10 cu. cm. of solution A). Example. Nine and nine-tenths cubic centimeters of solution B correspond to 10 cu. cm. of solution A. After acidulation with sulphuric acid, 100 cu. cm. of the water under examination is mixed with 15 cu. cm. of solution B and boiled. The red fluid is decolorized by the 10 cu. cm. of solution A. To restore a faint red tint 4.4 cu. cm. of solution B must be added. Estimation: 15 + 4.4 = 19.4; 19.4 9.9 = 9.5. Therefore, for the oxidation of the organic Substances in 100,000 parts of water (9.5 X 3-i6) : 9.9 = 3.008 of potassium permanganate, or (6.5 X 0.8) : 9.9 = 0.77 part of oxygen are necessary. Bad drinking-water, espe- cially when it contains much organic matter, should never be used in its native state, but particularly not at a time when epidemics of typhoid fever, of cholera or of dysentery prevail or threaten. It should be urgently advised that the water be thoroughly boiled previously, as by this means the germs of infection are destroyed. The resulting insipid taste can be readily improved by means of effervescent powder, sugar or fruit- juice. STRUCTURE AND SECRETORY ACTIVITY OF MAMMARY GLANDS. 417 STRUCTURE AND SECRETORY ACTIVITY OF THE MAMMARY GLANDS. About twenty milk-ducts open separately on the tip of the nipple, and just in advance of their mouth present an oval dilation, the lacteal sinus, generally ex- panded laterally. Each undergoes dendritic ramification and passes to a spe- cial lobe of the gland, which is bound together by loose interstitial connective tissue. Only at the time of lactation do all of the terminal branches of the milk- ducts lead to round glandular acini arranged in groups. Each vesicle has a membrana propria, upon which externally is a network of star-shaped connective- tissue cells, and internally a single layer of somewhat flattened, polyhedral and nucleated secretory cells. According to the degree of secretory activity of the acinus its lumen, at times narrow, at other times wide, is filled with a fluid in which float round, shining fat-granules (milk). Fibrillary connective tissue, principally arranged in a circular manner, and transversed externally by fine elastic fibers, forms the wall of the glandular ducts, which are lined by cylindrical epithelium. In the smallest of these a membrana propria can yet be recognized, which is continuous with that of the terminal vesicle. During the first days following delivery (as well as before it), the breasts secrete little milk of considerable consistency and yellowish color (colostrum) , in which large cells completely filled with fat-granules are present (colostrum-corpus- cles). The latter appear also later on, when the discharge of the milk has for a time been discontinued. Sometimes a nucleus is recognizable in the cells, FIG. 137. /, Acinus of the mammary gland, inactive; II, during the formation of milk: a, b, milk-globules; c d e, colostrum-corpuscles; /, pale cells (from the dog). rarely ameboid movement (Fig. 137, c, d, e). The normal secretion of milk, appearing in the course of three or four days, is a productive activity of the gland- cells. Heidenhain and Partsch found the secretory cells in the inactive gland (Fig. 137, 7) to be flat, polyhedral and mononuclear; on the other hand, in the active gland often polynuclear, cylindrical, higher, and richer in albumin and granules (Fig. 137, //). The free edge, turned toward the cavity of the acinus, undergoes characteristic changes during secretion. There are formed in this part of the cells fat-granules, which are thrown off during secretion, together with the de- tached cell-margin. In part the nuclei also, degenerate, their product likewise passing over into the milk (nuclein-content of milk). The same cells appear to be able to perform the secretory process repeatedly, undergoing regeneration during the period of rest. According to Bizzozero, Benda, Michaelis and Unger, the cells actively produce the fat-granules and throw them off. Leukocytes containing fat-granules are, further, found in milk, representing colostrum-corpuscles, and isolated, pale cells (/). Some' milk-globules still have shreds of cell-substance on their surface (6) . With respect to the formation of the individual constituents of milk, H. Thierfelder, who exposed fresh mammary t lands to digestive processes immediately after death, found that during the igestion of the gland at the temperature of the body a reducing substance, probably milk-sugar, was formed as a result of fermentative activity. The mother-substance (saccharogen) is soluble in water, but not in alcohol or ether; it is not destroyed by boiling and is not identical with glycogen. The ferment forming milk-sugar seems to be fixed in the glandular cell, as it does not pass over into the milk or into a watery extract of the gland. During the digestion 27 418 STRUCTURE AND SECRETORY ACTIVITY OF MAMMARY GLANDS. of the mammary gland at the temperature of the body casein also is formed as a result of a fermentative process, and probably from serum-albumin. This ferment is present in the milk. The mammillary areola and the nipple are characterized by pigmentary deposits in the cells of the rete Malpighii (during pregnancy more abundant and of greater extent) and by large papillae in the cutis, some of which contain tactile corpuscles. Numerous unstriated muscle-fibers in the deep layers of the corium and in the subcutaneous tissue (always free from fat) surround the milk-ducts of the nipples and in part also pass longitudinally to the tip of the nipple. The glands of Mont- gomery, about the size of a millet-seed, situated during lactation in the mam- millary areola, are small, nodular, prominent, subcutaneous milk-glands, with a special duct of evacuation at the summit of each nodule. Arteries enter the mammary gland from different directions. Their branches do not accompany the glandular ducts. Capillaries arranged in a network sur- round the glandular acini and anastomose by means of small arteries and veins with those of the neighboring vesicles. In the mammillary areola the veins are arranged in the form of rings (circles of Haller) . The nerves of the mammary gland arise from the supra-clavicular and the second, fourth and sixth intercostals. They pass in part to the skin of the gland and of the highly sensitive nipple, in part to the vessels, and in part to the unstriated muscle-fibers of the nipple and to the glandular vesicles themselves, in which their mode of termination is, however, as yet unknown. In connection with the investigations of the mammary glands great credit belongs to C. Langer. Lymphatics are found close about the alveoli, often distended to their utmost, and from them material for the formation of milk appears to be derived. Comparative. From ten to twelve nipples are found in rodents, insectivora and carnivora ; others among these animals have only four. Pachyderms and rumi- nants generally possess from two to four on the abdomen ; the carnivorous whale has two at the side of the vulva. Apes, bats, herbivorous whales, elephants and sloths resemble man; the half-apes have from two to four nipples. The duck-bill (ornithorhynchus paradoxus) possesses tubes arranged in groups (similar to skin- glands) , which open without nipples upon a hairless flat area of skin. The mar- supials carry their undeveloped young in a muscular duplicature of the skin of the abdomen, in which the nipples are situated. In them and in the duck-bill there is a compressor muscle of the mammary gland, which promotes the evacua- tion of milk. Development of the Breast. The first indication of the breasts consists on each side in a transitory elevation passing downward on the lateral aspect of the thorax, and of which subsequently there remain only punctate and nodular formations, the precursors of the breasts. The further development of the latter begins in both cases as early as the third month; between the fourth and fifth a number of simple tube-like glandular ducts arranged radially are already present beneath the hairless, excavated mammillary areola. In the new-born the ducts already exhibit two or three branches, and they are provided with dilated extremities. In both sexes the ducts divide in a dendritic manner until the twelfth year, though without the development of actual acini. In girls who have reached puberty this Branching proceeds rapidly and extensively, although also in them the gland, rich in connective tissue, exhibits the formation of acini only at ,the periphery, while only with the occurrence of pregnancy do characteristic acini develop also in the center of the body of the gland along with relaxation of the connective tissue. In the climacteric period all of the acini and numerous small milk-ducts dis- appear. In the adult man the mammary gland usually resembles that of the new- born, having undergone involution after puberty. Supernumerary nipples on the breast are of interest as representing independent openings of individual milk-ducts . Supernumerary glands and nipples (hypermastia and hyperthelid) arranged in part irregularly and in part regularly in rows, like the dugs of the sow, point to their original multiple beginning and are worthy of note as points of resemblance among animals. The situation of a breast in the axilla, on the back, on the acromion or on the tibia is a curiosity. A slight secretion from the breast of the new-born (witches' milk) is normal. On the other hand, suckling performed by a man is to be included among the greatest rarities. According to Aristotle buck- goats sometimes give milk (noted also by Schlossberger) , as do also calves after their dugs have been frequently sucked, and goats that have not been covered, when their udders are irritated by nettles. MILK AND MILK-PREPARATIONS. 419 The evacuation of milk (from 500 to 1500 cu. cm. in twenty-four hours) is due not alone to the purely mechanical act of suction, but also to the functional activity of the mammary gland. The latter consists primarily in erection of the nipple, the smooth muscle-fibers of which exerting pressure on the sinuses of the ducts, so that the milk may spurt forth in a stream. Moreover, the glandular structure itself is reflexly stimulated to more active secretion through irritation of the sensory nerves of the nipple. From the suddenly dilated glandular vessels a transudate pours abundantly into the gland, by which, admixed with the milk-corpuscles and transformed into milk, it is discharged. The amount of the secretion depends thus upon the degree of blood-pressure. Accordingly, not only the milk stored up in the breast is sucked out, but during the process of suction secretion is accelerated. "The breast is willing, ' ' as the nursing women say. Only in this manner can be explained the speedy arrest of the secretion of milk in connection with sudden emotional excitement .which (as anger, fright, etc.) acts, as is known from experience, on the vasomotor nerves. Laffont saw, following stimulation of the mammary nerve of a bitch, erection of the nipples, dilatation of the vessels and secretion of milk. After section of the external spermatic nerve in goats, Eckhard noted absence of erection of the dugs, although the formation of milk suffered no interruption, which appeared only after section of the nerves on both sides. Continued stimulation of sensory nerves diminishes the secretion. The rarely observed condition of galactorrhea is perhaps to be considered as a sort of paralytic secretion similar to the analogous secretion of saliva. Heidenhain and Partsch noted increased secretion in dogs when, following section of the glandular nerves, strychnin or curare was in- jected. Atropin decreases the amount of milk. The slight milk-fever appearing with the commencement of the secretion of milk is probably due to increased stimulation of the vasomotors, whose activity must further be considered in relation with the transposition of the mass of blood out of the pelvic cavity after birth. MILK AND MILK-PREPARATIONS. Milk must be designated a complete food, in which all of the constitu- ents are present in such proportion that the body can thrive upon it. Ac- cording to Johannessen the proportions in human milk are as follows: Albumin i, fat 2, sugar 4.2; in cow's milk: albumin i, fat i, sugar 1.43. Of the milk relatively more fat is absorbed in the intestine than albuminates. Human milk is utilized up to 91.6 per cent., cow's milk to 90 per cent. Milk is opaque, bluish white, with a sweetish taste and a characteristic odor, probably due to peculiar odoriferous bodies in the cutaneous secretion of the gland. It has a specific gravity of from 1.030 to 1.032. On standing numerous butter- globules collect on the surface as cream, beneath which is a watery bluish layer. Human milk has always an alkaline reaction; cow's milk is at times alka- line, sometimes acid, t and sometimes amphoteric. The milk of carnivora is always acid. Milk consists of the fluid (milk-plasma, plasma lactis) and the morphological constituents suspended in it, among which the milk-globules predominate. If the milk be clotted, the cheese-cake (placenta lactis), which consists of coagulated casein, containing milk-globules, separates from the whey (serum lactis). The latter contains some dissolved albumin, milk-sugar and most of the salts. Milk-globules or Butter-globules. Microscopically, milk contains innumerable small globules (Fig. 137). Colostrum-corpuscles and epithelium from the milk- ducts are not common in mature milk. The milk-globules and the swollen casein cause, on account of the reflection of light, the white color and the opacity of milk. The milk-corpuscles consist of butter-fat and are apparently surrounded by a thin layer of casein (haptogenic membrane) . That the milk-corpuscles are actually surrounded by a capsule of casein has lately been definitely denied. Formerly, the following observations were offered in support of the presence of the capsule: if acetic acid, which dissolves the casein- capsule, be added to a microscopic preparation, the milk-globules run together in fat-droplets. Further, if cow's milk be shaken with potassium hydroxid, which destroys the casein-capsule, and then be mixed with ether, the milk becomes clear and transparent, as the ether dissolves all of the fat-granules. Previously to the treatment with potassium hydroxid or acetic acid, the ether is incapable of setting free the fat in cow's milk from its capsule; in the case of human milk the addition of ether and shaking alone suffice. Other investigators, however, 420 MILK AND MILK-PREPARATIONS. deny the presence of the casein-capsule ; according to them milk is a simple emul- sion, permanently maintained as such by means of the colloid casein, which is simply swollen in milk-plasma. The treatment of milk with potassium and ether renders the casein of the plasma unfitted to maintain the emulsion of the milk permanently. The fats of the milk- globules (human) are the triglycerids of stearic, palmitic and oleic acids, in lesser amount of myristic, capric, caprylic, caproic and butyric acids. In addition there are found traces of formic acid and cholesterin. By means of long-continued beating of milk (churning) , and even more readily of cream, the fat of the milk-globules (after rupture of the casein-capsule) is ob- tained as butter in coherent masses. Butter is soluble in alcohol and ether, and is purified by melting at 60 C., or by washing with water at 40. On standing in the air it becomes rancid, from the glycerin of the neutral butter-fats being decomposed by the action of germs into acrolein and formic acid, which, with the volatile fatty acids, give the odor. The milk-fluid (plasma lactis) is clear, somewhat opalescent and contains proteids, chief among which is casein, together with a small amount of lact- albumin and lacto globulin and the opalescent opalisin, a little nuclein, phospho- carnic acid and a trace of diastatic ferment (in human milk) . Casein is retained in the filtration of milk by means of fresh animal membrane or by means of clay cylinders. It can also be completely precipitated out of human milk by means of saturation with magnesium sulphate, from cow's milk by means of a little acetic acid. Quantitative Determination in Cow's Milk: Twenty cubic centimeters of cow's milk are diluted with 60 cu. cm. of water, and 30 cu. cm. of a i in 1000 sulphuric-acid solution are added with stirring, precipi- tating the casein of cow's milk. After five hours filtration is practised, the filter is washed with water, twice with alcohol and fifteen times with ether, and it is then dried and weighed. The casein can be completely precipitated by addition of alum at a temperature of 37 C. Magnesium sulphate then precipitates the globu- lin in the filtrate. Globulin and albumin together are precipitated from the filtrate by means of tannic acid. The albumin in milk coagulates on boiling; in addition the free surface be- comes covered with a skin of insoluble casein. The plasma contains, further, milk-sugar, a carbohydrate resembling dextrin, lactic acid?, lecithin (if times as much as in cow's milk), urea, traces of kreatin, kreatinin, xanthin-bodies (potassium sulphocyanid in cow's milk) ; sodium chlorid, potassium chlorid, alkaline phosphates, calcium and magnesium sulphates, alkaline carbonates and in addition traces of iron, metallic fluorids and silica, carbon dioxid, nitrogen, oxygen and ammonia. Human milk contains numerous staphylococci. The curdling of milk consists of a coagulation of the casein. The latter is combined in the milk with calcium phosphate, and is therefore soluble. Acids, which remove the calcium phosphate from the casein, cause coagulation of the casein ; lactic acid acts most readily in this connection, then hydrochloric, nitric, sulphuric, acetic and phosphoric acids. Acetic and tartaric acids, when added in excess, re- dissolve the precipitated casein. Human milk is not curdled by all acids, but only by means of two or more drops of o.i per cent, hydrochloric or 2 per cent, acetic acid. Heating above 130 C. coagulates the milk, acids being formed from milk- sugar as a result of the action of heat and the contained casein becoming more coagulable. The spontaneous curdling of milk after standing for some time, especially in the heat, results from the formation of lactic acid by the bacillus acidi lactici, which transforms the neutral alkaline phosphate into acid phosphate, removes the calcium phosphate from the casein and thus precipitates it. The sugar is transformed into lactic acid and carbon dioxid. The bacillus furnishes the stimulation for this decomposition, while the casein of the milk is the actual fermenting body. By means of the lab-ferment milk of alkaline reaction may be coagulated (sweet whey) . This ferment decomposes the casein in the precipitated cheese and the scanty but readily soluble whey-albumin. The lab-coagulation is then quite different from the others. It takes place only when calcium-salts are dissolved in the milk. If these are precipitated by means of potassium oxalate, the lab- ferment no longer causes coagulation in the fluid; this latter, however, occurs again as soon as calcium chlorid is added. Boiling (by destroying lower organisms) , sodium bicarbonate ( T Vo o) ammonia, salicylic acid GfiW), also glycerin and ethereal oil of mustard, prevent spontaneous coagulation. Fresh milk renders tincture of guaiac blue; boiled milk does not. After standing for some time in the air milk gives off carbon dioxid and absorbs MILK AND MILK-PREPARATIONS. 421 oxygen. At the same time, as a result of the activity of germs that develop rapidly in the milk(?), an increase of the fat, together with that of the alcoholic and ethereal extracts at the expense of the casein, is brought about. Accord- ing to Schmidt-Mulheim some casein is transformed into peptone but onlv in unboiled milk. Milk-analysis. Every 100 parts of milk contain: HUMAN. Cow. GOAT. Ass. Water 88.3 88.0 86.25 89.01 Casein 0.9-1.2 \ 3.0 2.53 ) Albumin 0.3-0.5 f I ' 1 03 i 26 / 3>s ? jitter 3-21 3-5 4-34 1.85 Milk-sugar 4.67 4 .c * 78 1 Salts 0.2 0.7 0.65} 5-05 Colostrum contains much serum-albumin and little casein, but, on the other hand, all other solid substances in larger amount, especially the butter. Pfliiger and Setschenow found in 100 volumes of milk the following substances by volume: carbon dioxid from 5.01 to 7.60; oxygen from 0.09 to 0.32; nitrogen from 0.70 to 1.41. The carbon dioxid can in part be displaced only by means of phosphoric acid. Among the salts, those of potassium preponderate over those of sodium (as in the red blood-corpuscles and in meat) ; also a considerable amount of calcium phosphate is present, for the formation of the bones of the infant. Wildenstein found in 100 parts of ash from human milk sodium chlorid 10.73; potassium chlorid 26.33, potassium 21.44, calcium 18.78, magnesium 0.87, phosphoric acid 19, ferric phosphate 0.21, sulphuric acid 2.64, silica a trace. The amount of salts is influenced by that in the food. Milk exhibits no difference in the amount of albumin before and after nursing. The amount of sugar, however, diminishes after nursing, while the fat increases con- siderably. With the progress of lactation, albumin appears most abundantly in the first six months, in lesser amount in the second six months, and after the first year it decreases still more. The amount of fat varies, but rather increases after the first year. The sugar exhibits a pretty uniform, inconsiderable increase. In primiparae the amount of solid constituents (9.67 per cent.) is greater than in multipart (8.56 per cent.). Young mothers form more albumin and fat, older mothers more sugar. A starchy diet yields a fatter milk, while with a proteid and fatty diet the amount of albumin and of sugar increases. Camerer and Spldner found in milk a body resembling the basis of bone, together with hitherto unknown bodies consisting of carbohydrates combined with proteids. If it be necessary to employ the milk of animals, it should be noted that cow's milk (best when containing much fat) must be diluted with water and mixed with milk-sugar. Heubner and Hofmann recommend for children from one to nine months old, as a general rule, only one mixture, consisting of i part of cow's milk and i part of a solution containing 69 grams of milk-sugar in i liter of water. Soxhlet recommends a mixture of 2 parts of cow's milk and i part of a 12.3 per cent, solution of milk-sugar. The casein of cow's milk varies qualitatively; further, it appears in larger flakes and is, there fore, more difficult of digestion than the small-flaked casein of human milk. The casein of human milk does not split off paranuclein in the process of digestion, as does that of cow's milk. Boiled cow's milk is somewhat more difficult of digestion than unboiled cow's milk, but, never- theless, because sterilized, is to be preferred. The milk should be boiled for ten minutes, be cooled quickly to below 18 C. and be kept cool. In the case of chil- dren more than nine months old, the addition of water is progressively diminished. Cow's milk may also be diluted with advantage with beef-tea. For children that cannot take milk, v. Liebig has recommended especial soups prepared from cow's milk, water, wheat-flour, hop-flour and sodium bicarbonate. The starch is trans- formed, in the course of preparation, into sugar and dextrin. The more rapid the growth exhibited by mammals the richer is their milk in albumin. Milk-tests. The amount of cream is measured by permitting the milk to stand for twenty-four hours in a cool place in a high glass cylinder graduated into 100 parts. The cream that collects on the surface should amount to from 10 to 14 volumes per cent. The specific gravity of whole cow's milk is between 1029 and 1034, of skimmed milk between 1032 and 1040. It is determined by means of the areometer at a temperature of 15 C. Every degree Celsius more or less makes a difference of -0.1 or + 0.2 on the areometer. Should only an approximative 422 MILK AND MILK-PREPARATIONS. estimation be desired, the amount of sugar both in the whey as well as in the whole milk diluted with water can be titrated directly by means of Fehling's solution (i cu. cm. of which corresponds to 0.0067 gram of milk-sugar) ; or the amount in the whey may be determined by means of the polarization-apparatus. If the estimation is to be made with exactness, the proteid must be removed from the whey; and in addition the fat-globules dissolved out of the whole milk, and the fat extracted. The amount of water, as compared with the amount of milk-cor- puscles (fat) the latter should not be less than 3 per cent, in whole milk, and i$ per cent, in half-skimmed milk is determined by means of the lactoscope (the diaphanometer of Donne, modified by Vogel and Hoppe-Seyler) . This consists of a glass vessel i cm. in diameter with plane parallel walls. A measured quantity of milk is introduced into the vessel and water added from a graduate until the flame of a lighted candle placed about a meter behind the apparatus can be distinctly seen outlined (in a dark room) with the eye placed directly in front of the appara- tus. In such an experiment from 70 to 85 cu. cm. of water are needed for each cubic centimeter of good cow's milk. Feser's galactoscope also is serviceable in the examination of milk, even in the hands of the laity. The following substances pass into the milk: fat taken with the food, numerous odorous substances (anise, vermouth, garlic, etc.) ; chloral hydrate, opium, indigo, salicylic acid, iodin, iron, zinc, mercury, lead, bismuth and anti- mony. In cases of osteomalacia the amount of calcium in the milk is increased. Potassium iodid diminishes the secretion of milk. Abnormal admixtures include hemoglobin, biliary pigments, mucin, blood- corpuscles, pus, fibrinous clots, tubercle-bacilli and other bacilli. Numerous germs develop in evacuated milk, of which the bacillus cyanogenus, which occurs rarely, gives the milk a sky-blue color. It is the milk-serum that is blue, not the germ. There are also schizomycetes that produce bluish-black and green colors. Red and yellow milk are also observed as a result of similar action by other chromogenic schizomycetes. Red milk is due to the notorious micrococcus prodigiosus, which is itself colorless, and also to the bacterium erythrogenes ; yellow milk, to the bacillus synxanthus. Some of the pigments formed seem to be related to the aniline dyes and others to those belonging to the phenol-group. As the possibility of the entrance also of other pathogenic germs cannot be ex- cluded, the milk should be sterilized by boiling. The rennet-like activity of bacteria is widespread, so that they coagulate and peptonize casein and finally cause further decompositions. Thus the butyric- acid bacilli first cause the coagulation of the casein, which they then peptonize and later decompose, with the development of ammonia. Milk becomes viscous from the action of the bacillus lactis viscosus, perhaps in other ways, just as beer and wine may become "long." Preparations of Milk. i. Condensed Milk. Eighty grams of cane-sugar are added to each liter of milk, the mixture evaporated to one-fifth its volume and then sealed in tin cans while hot. For the use of nursing infants a teaspoonful is dissolved in a pint of cold water and then boiled. 2. As a food replacing albumin A. Salkowski recommends the following prep- aration of casein: Casein 20 parts, sodium phosphate 2 parts, water 200 parts, or the soluble ammonia-compound prepared by conducting ammonia over casein (eucasin) ; Rohmann advises acid casein-calcium 3 grams, milk-sugar 4.5 grams, di-sodium phosphate 0.375 gram, monopotassium phosphate 0.153 gram, calcium chlorid 0.04 gram, potassium chlorid 0.3 gram, magnesium acetate o.oi gram, water 100 grams. 3. Koumiss and Kefyr. The Kirghese are accustomed to produce alcoholic fermentation in mare's milk, and the Caucasian mountaineers do the same with cow's milk. As a result of the addition of sour milk, which contains the bacterium lacticum and the bacillus caucasicus, the unfermentable milk-sugar is transformed into fermentable glucose, and by the action of yeast, which is present in an ad- dition of completed koumiss, alcoholic fermentation of the glucose takes place, the mixture being vigorously stirred. Koumiss contains from two to three per cent, of alcohol. The casein, which is precipitated at first and later is partly dissolved again, is transformed into acid-albumin and peptone. The kefyr-fungus (dispora caucasica) also gives rise to a similar preparation, in part containing peptones. In addition to the kefyr-fungus, there is also found the bacterium lacticum and a schizomycete that peptonizes casein, as well as a streptococcus that forms lactic acid and another organism that ferments milk-sugar. Koumiss and kefyr are also prepared at some health-resorts. 4. Cheese is prepared by coagulating skim-milk (poor cheese), or whole milk EGGS. 423 (fat cheese), by means of rennet, permitting the whey to run off and well salting the coagulated mass. After some time the cheese ripens, the casein, probably with the formation of sodium albuminate, becoming soluble in water once more. In some kinds of cheese liquefaction occurs, with the formation of peptone and diastatic ferment as a result of the action of the cheese-spirillum (spirillum tyrogenum). On further decomposition, leucin and tyrosin appear. The amount of fat in the cheese increases, while that of casein diminishes. Later on, the fats decompose; the volatile fatty acids yield the characteristic odor. The formation of peptone, leucin, and tyrosin and the splitting up of the fats suggest the digestive processes. Cheese contains also saprophytic microbes. EGGS. Eggs also must be looked upon as a complete food, as the organism of the young bird is capable of developing from them. The yolk contains, as the characteristic albuminous body, vitellin; also an albuminate in the capsules of the yellow yolk-globules, the egg-casein, which is precipitated by means of a one per cent, solution of sodium chlorid, on combining with oxygen; nuclein from the white yolk; fats in the yellow yolk (palmitin and olein) ; cholesterin, much lecithin, and, as a product of decomposition, glycerophosphoric acid, grape-sugar; pigments (lutein), including one containing iron and related to hemoglobin; finally salts, qualitatively as in the blood, quantitatively as in the blood-corpuscles; gases. The white of the egg contains egg-albumin as the principal con- stituent, in addition to some globulin, mucin-matter and albumose, also small amounts of palmitin and olein, partly saponified by sodium; grape- sugar ; extractives ; finally salts that resemble qualitatively those of the blood and quantitatively those of the serum. There are, besides, traces of fluorin. On a diet of eggs and also on a diet of roast meat, relatively more of the nitrogenous constituents are absorbed than of the fats. MEAT AND MEAT-PREPARATIONS. In the form in which it is consumed, meat contains, in addition to the proper muscular tissue, an admixture in greater or lesser amount of the elements of fatty, connective and elastic tissues. Beef freed from fat and dried contains, according to Argutinsky, carbon 49.6, nitrogen 15.3, hydrogen 6.9, ash 5.2, oxygen and sulphur 23 per cent. According to H. Schulz the amount of sulphur present is i.i per cent, of the dried muscle. The chemistry of muscle is fully discussed on p. 548. The proteids of muscle are contained in the contractile substance and in part in the saturating fluid. The fats are derived for the greater part from the inter-fibrillary fat-cells, the lecithin and cholesterin chiefly from the muscle-nerves. The gelatin-yielding substance is supplied by the con- nective-tissue fibers of theperimysium, the perineurium, the vessel- walls and the tendinous parts. The red coloring-matter, which is present in varying amount even in the muscles of the same animal (red muscles and white muscles), is hemoglobin. In addition, some muscles, for example the heart, contain the related substance, myohematin. Elastin is present in the sarcolemma, the neurilemma and the elastic fibers of the perimysium and the vessel- walls. Keratin, in small amount, is de- rived from the endothelium of the vessels. The following are to be con- sidered as end-products of the retrogressive metamorphosis of the muscle- substance proper, in which also they occur in greatest amount: k;reatin 424 MEAT AND MEAT-PREPARATIONS. 25 per cent., kreatinin, sarcin, xanthin (especially in fasting pigeons), carnin (oxidizable into xanthin, present in meat-extract), uric acid (urea o.oi per cent.). There are present further inosite (abundant in the muscles of alcoholics), inosinic acid (inconstant), phospho-carnic acid, resembling nuclein and decomposing into carnic acid (C 10 N 3 O 5 H 15 ), and' a carbohydrate, and also some non-coagulable albumin, taurin (especially in cold-blooded animals), some grape-sugar, glycogen (0.43 per cent.) abundantly in fetal muscles. Further, meat contains lactic acids together with volatile fatty acids. Among the salts the potassium- compounds with phosphoric acid predominate; magnesium phosphate predominates over calcium phosphate. According to Schlossberger and v. Bibra 100 parts of meat contain the following: Ox. CALF. DEER. PIG. MAN. CHICKEN. CARP. FROG. Water Solids Soluble albu- ] 77-5 22.50 78.20 21.80 74.63 2 5-37 78.30 21.70 74-45 25-55 77-30 22.70 79.78 20.22 80.43 *9>S7 min . ! Coloring- mat- f 2. 2O 2.6o 1.94 2.40 *-93 3- 2-35 1.86 ter. ....... J Glutin I. 3O 1. 60 o ^o 0.80 o A *T i . 20 1.98 2 A8 Alcoholic extract * ' O 1.50 1.40 W 'O W 4.75 1.70 ^.U/ 3-71 1.40 3-47 4 .q.0 3.46 Fats I 3O o o n i ii O I O Insoluble albu- *JV 2.30 min, vessels, etc 17 CQ 16. 20 16.81 16.81 T C? A 1 6 ^o T T 2 T II 67 / *D W - 1 JO4 1 x 6 i zoo parts of meat-ash contain the following: HORSE. Ox. CALF. PIG. Potassium carbonate Sodium. 39-40 4 86 35-94 34.40 37-79 Magnesium 3 88 35 4 81 Calcium Potassium i. 80 o 1 i-73 e. e.6 x -4o 1.99 7-54 Sodium ) Chlorin f Iron oxid Phosphoric acid 1.47 1. 00 4.6 1 A. oo u 4.86 j 0.98 10.59 0.27 A& I? 0.40 0.62 0-35 Sulphuric acid. . . . O 3O o4-3 u 44-47 Silicic acid Carbon dioxid 61 2.07 Q fNrt 0.81 Ammonia * " * * 0.15 Potassium and sodium may partially replace each other. The flesh of the pike contains almost twenty times as much calcium as does beef. The amount of fat in meat is exceedingly variable in accordance with the state of nutrition of the animal. In 100 parts of human flesh, after the visible fat has been cut away, it is from 7 to 15; in beef from 11 to 12; in veal 10.4; in mutton 3.90; in wild goose 8.80; in chicken 2.50. The amount of extractives is most abundant in the flesh of those animals that exhibit vigorous muscular activity, therefore especially in game. After severe muscular exertion the extractives increase, and at the same time sarco- lactic acid is formed, the meat as a result becoming tender and more pleasant MEAT AND MEAT-PREPARATIONS. 425 to the taste. Among the extractives there are some that have a stimulating influence on the nervous system, such as kreatin, kreatinin, etc., and some that give to the flesh the pleasant characteristic taste (osmazome). The latter is due in part also to the various fats in the meat, and at times it appears distinctly only on preparation. In 100 parts of meat the amount of extractives is in man and in pigeons 3, in deer and in ducks 4, in swallows 7. Preparation of Meat. As a general rule the flesh of younger animals is more tender and more easily digested than that of older animals, because the sarcolemma. the connective tissue and the elastic constituents are less tough. Further, after being allowed to hang for a while, the flesh is still more tender, because the inosite is converted into sarcolactic acid, the glycogen into sugar, and the latter into lactic acid, so that the constituents of the meat undergo a sort of maceration. Meat is further always more easily attacked by the digestive juices when in a finely divided state than when in large pieces; and, finally, it should be noted that adequately boiled, steamed, broiled or roasted meat is easily digestible, although not so rapidly as raw meat. In the preparation the heat should not be too in- tense or too long continued, because in such an event the muscle-fibers become hard and much shrunken. On the other hand, those pieces of meat that are heated to about 60 or 70 C., such as the pieces from the middle of a large roast that yet have a rosy but not bloody appearance, are most easily digested, as this temperature is quite sufficient with the aid of the acid in the meat to transform the connective tissue into gelatin. Thus, the meat falls apart and the separate fibers are readily isolated in the stomach. To obtain a piece of good, readily digestible meat, a large cubical block is taken and its surface is suddenly exposed to strong heat by frying in fat or immersion in boiling water. In this manner a firmly coagulated layer of albumin forms on the surface, which no longer allows the juices of the meat to escape from the interior. The reddish, juicy parts from the interior of a piece of meat thus prepared are the most nutritious and the most readily digested, while the hard and much shrunken outer crust resists the digestive juices for some time. Meat-broth is most suitably prepared by permitting thoroughly chopped meat to stand for some hours in cold water and then boiling, v. Liebig found that out of 100 parts of chopped beef thus treated, but 6 parts pass over into the cold water. Of these, 2.95 parts are again precipitated as coagulated albumin and for the greater part skimmed off and thrown away, so that only 3.05 parts remain dissolved. Of 100 parts of chicken 8 parts are extracted, of which 4.7 are coagulated and 3.3 parts dissolved in the broth. By protracted boiling a part of the coagulated albumin may again pass into solution. The dissolved substances are: i. Inorganic salts of the meat, of which 82.27 P er cent, pass over into the broth. The boiled-out meat retains principally the earthy phosphates. 2. Kreatin, kreatinin, lactates and inosinates, which give to the meat-broth its stimulating and nerve-strengthening power, as well as a small amount of extract- ives of pleasant taste and some glycogen. 3. Gelatin, which is obtained in consid- erable amount from the flesh of younger animals. In accordance with the facts and figures presented, meat -broth is thus to be considered really as merely a highly valuable stimulant, acting as a re- storative to the muscles, but not as a food in the ordinary sense of the word, for the constituents of the meat-extract and the kreatin leave the body in the urine in a practically unchanged condition. From larger pieces of meat cooked in the broth even fewer constituents are obtained. Such cooked-out meat ac- cordingly, provided it is not much shrunken by excessive boiling and therefore rendered difficult of digestion, possesses a high nutritive value, which is usually underestimated by the laity. On the other hand, the preparation of meat-broth at home is a real luxury, its so-called strength in the sense of the laity being a pure illusion. J. v. Liebig' s Meat-extract is a fat-free meat-broth containing, however, some gelatin and glycogen, and also about 30 per cent, of albumoses and peptone. It is prepared from finely chopped beef or mutton, in parts of South America and Australia where beef is plentiful, and is evaporated in wide dishes on a water- bath to the consistency of an extract. By solution in water a cheap meat-broth can thus be readily obtained: i kilogram of beef yields 31 grams.. By boiling the solution with bones (gelatin), some beef-fat, pot-herbs and addition of salt a beverage completely replacing fresh broth is obtained. The so-called "bouillon- tablets" on sale consist almost entirely of desiccated gelatin, which is obtained to the extent of about 28 per cent, from bones boiled in Papin's pots under high pressure. These alone, when dissolved in hot water, naturally cannot replace 426 VEGETABLE FOODS. meat-broth; they can, however, be advantageously employed in conjunction with v. Liebig's meat-extract. In boiling, meat loses weight, principally through loss of water, as follows: beef 15 per cent., mutton _io per cent., chicken 13.5 per cent. In roasting the same kinds of meat the loss is respectively 19 per cent., 24 per cent., 24 per cent. J. v. Liebig's " Infusum carnis jrigide paratum" is prepared by mixing finely chopped meat with i : 1000 hydrochloric acid (3 cu. cm. of fuming hydrochloric acid to 1000 cu. cm. of water), stirring frequently and expressing after some hours. The almost tasteless fluid, which, in addition to the constituents of the broth, is also rich in albumin, is often useful in cases with enfeeble digestion. Albumin is, however, precipitated by the addition of sodium chlorid or by boiling. Leube and J. Rosenthal reduced such a mixture of hydrochloric acid and meat to a gelatinous spongy condition (containing but little peptone) by heating under high pressure in hermetically sealed vessels. The meat-solution thus obtained is employed advantageously in cases of weak stomach. Of other methods of preservation there are yet to be mentioned: the canning in its own juices of meat boiled at a temperature of 100; the drying of fat-free meat cut into long narrow strips (the pemmican of the Indians) ; dried, powdered, salted beef (carne pura). C. v. Voit discovered that the nutritive value of meat is not impaired to any great degree in the process of pickling. He found in pickled meat, in addition to increase in sodium chlorid, a loss of water of 10.4 per cent., of organic matters 2.1 per cent., of albumin i.i per cent., of extractives 13.5 per cent., of phosphoric acid 8.5 per cent. The practice of smoking is based upon the antiseptic action of the smoke. Poor quality and decomposition of meat may result from the development of the alkaloids of putrefaction (ptomains) , as well as from the action of bacteria. Such a condition should always cause rejection of the meat. Although it is often enough consumed without bad result, as the popularity of the "haut gout" or "gamey taste" demonstrates. At least, the meat, before being eaten, should always be thoroughly boiled. The decomposition of sausages and similarly pre- pared meat at times results in the development of a peculiar and even fatal poison, the sausage-poison. Occasionally the decomposition of meat, particu- larly also of fish, gives rise to a peculiar actively phosphorescent light, due to the development of lower organisms. The use of such meat, however, does not seem to be directly injurious. A knowledge of the occurrence of the trichina spiralis in pork is highly important; also of bladder-worms varying in size from a pea to a bean in pork and beef, the development of which into tapeworms is dis- cussed under Reproduction. The cysticercus of bothriocephalus latus is found in the pike. VEGETABLE FOODS. The nitrogenous constituents of plants are less readily absorbed than those of animal foods. Nevertheless the former may completely replace the animal proteids, provided they contain an equal amount of nitrogen. Carbohydrates, starch and sugar are quite completely absorbed and even some cellulose is digested. The greater the amount of fat in vegetable food the less the carbohydrates are digested and absorbed. Among the vegetable articles of food the cereals occupy the first place. They contain proteids, starch, and salts, together with water to about 14 per cent. The nitrogenous gluten is most abundant beneath the capsule, so that the use of finely ground bran in coarse bread seems plausible for good digestive organs; although the varieties of bread that contain a considerable amount of bran are digested with appreciably greater difficulty, as the cellulose-membrane of the gluten-layer is scarcely dissolved in the process of digestion. Rye-bread is assimi- lated with greater difficulty than wheat-bread. For commercial bread a mixture of both kinds of flour is advisable. Quantitative composition: ioo parts of dry flour contain: 100 parts of cereal ash contain: Albuminates. Starch. Red Wheat. White Wheat. Wheat 16.52% 56.25% 27.87 Potassium carbonate 33.84 Rye 11.92 60.91 15-75 Sodium .... Barley 17.70 38.31 1.93 Calcium 3.09 Corn 13-65 77-74 9.60 Magnesium 13. 54 Rice 7.40 86.21 1.36 Iron oxid 0.31 Buckwheat 6.8-10.5 65.05 49-36 Phosphoric acid 49.21 0.15 Silica .... VEGETABLE FOODS. 427 It is remarkable that in white wheat sodium is wanting and is replaced by other alkalies. Rye contains more cellulose and dextrin than wheat, but less sugar. Rye-bread is, as a rule, less porous. Barley and oats are much used as gruel, and in the North also mixed in bread. Oats contain a crystalline globulin (avenalin) , and a proteid soluble in alcohol and another soluble in alkalies. By admixture with water or neutral salts three other proteids are obtained as products of transformation. Rye and wheat yield one globulin (edestin) ; one albumin (leukosin) ; gliadin, forming gluten, and soluble in dilute alcohol; and glutenin (absent from rye), soluble in dilute acids and alkalies. Barley contains leukosin, edestin, hordein, corresponding to gliadin, and also other proteids. In the preparation of bread, flour is kneaded, together with water, to form dough, in which the gluten acts as a cementing substance, and to which salt and also yeast (saccharomyces cerevisiae) are added. Under the influence of heat the albuminates of the flour begin to undergo decomposition and the ferments act upon the swollen starch, which is partially transformed into sugar. The sugar undergoes further decomposition into carbon dioxid and alcohol, of which the first, forming bubbles in the stiff dough, causes this to become spongy. Certain bacteria also cooperate with the yeast to the same end. By the baking at 200 C. the alcohol is driven off and the dough is done. Much readily soluble dextrin is formed in the crust . In the preparation of sour bread, old sour dough, in which the sugar has partially undergone lactic- acid fermentation, is added instead of yeast, and as a re- sult, in addition to the alco- holic fermentation, the lactic- acid fermentation of the grape-sugar in the dough is also initiated. As in the transformation of starch into sugar, and the latter into car- bon dioxid and alcohol (which eventually escape) , material is directly lost; am- monium carbonate, which es- capes during the process of baking with the expansion of the dough, is added. This loss amounts to about one per cent.; with an average daily consumption of bread for each individual of 256 grams, the daily loss for 1,000,000 persons should equal 2500 kilograms of bread, or sufficient for 10,000 persons. J. v. Liebig proposes the use of sodium bicarbon- ate and hydrochloric acid for the same purpose ; then the dough will not have to be salted, because of the formation of sodium chlorid. Horsford's baking-powder (calcium phosphate and sodium bicarbonate) is also used. It permits the escape from the dough of the expanding carbon dioxid, the phosphoric acid of which is also useful to the body. The legumes contain much albumin. Beans contain two globulins readily soluble in salt-solutions the phaseolin of Ritthausen and phaselin. Peas and vetches yield in considerable amount a globulin, designated legumin by Braconnot, which is soluble in a solution of sodium chlorid, and also three other proteids. Legumes contain also starch, lecithin, and cholesterin, together with from 9 to 19 per cent, of water. Peas contain 28.02 per cent, of albumin and 38.81 of starch; beans 28.54 and 37.50; lentils 29.31 and 40 respectively. The last are richer in cellulose. Because of the deficiency in gluten no dough can be made from them, and therefore no bread. As a food for the mass of the people, these plants deserve the greatest consideration, because of the large amount of albumin they contain, although they may be a source of intestinal discomfort in consequence of the devel- opment of gas, as well as of the presence of indigestible cellulose. Leguminous flour, when mixed in different proportions with the flour of cereals (for instance in the form of Hartenstein's leguminose) , can be used with advantage in the feed- ing of children and debilitated persons. FIG. 138. Section through a Grain of Wheat: p, epidermis, with c, cuticula, m middle layer, qu transverse, sch tubular cells, br and n seed-membrane, Kl gluten, / starch. 428 CONDIMENTS. Maize contains three globulins, several albumins, and a proteid zein soluble in alcohol. Potatoes contain from 70 to 81 per cent, of water. In the juicy cellular tissue, which yields an acid reaction when fresh, from the presence of phos- phoric, malic and hydrochloric acids, there is present from 16 to 23 per cent, of starch, 2.5 per cent, of dissolved prpteids, consisting of one globulin (tu- berin), soluble in potato-juice, and some albumin, together with a trace of asparagin. The cell-capsules become swol- len when boiled, and are changed by dilute acids into sugar and gum. The "eyes" contain the poisonous sub- stance solanin. One hundred parts of potato-ash contain: potassium carbonate 46.96, so- dium chlorid 2.41, potassium chlorid 8.1 1, magnesia 13.58, calcium 3.35, phosphoric acid 11.91, sulphuric acid, derived from burned albuminates, 6.50, silica 7.17. Fruits contain as the prin- cipal food-constituents sugar and salts. Their characteristic taste is due to the organic acids. The gelatinizing substance of fruit-jellies is the soluble so- called pectin (CgjH^Og;;) , which can also be obtained artifici- ally by cooking from the pec- tose of unripe fruit, which is soluble with difficulty, and from carrots. Green vegetables are especially rich in salts that resemble the salts in the blood. For instance, unseasoned lettuce contains 23 per cent, of salts, spinach much iron. Of less importance in them are starch, dextrin, sugars and small amounts of albumin. FIG. 139. Section through Potato: k, cork; pi, plasma-containing cells, with small starch-granules; cr, protein crystalloid; s, starch. CONDIMENTS. COFFEE, TEA, CHOCOLATE, ALCOHOLIC DRINKS AND SPICES. Since the time of v. Bibra the term condiment has been applied to such articles of food as are used less because of their direct nutritive properties, than because of their agreeable action and stimulation, in part upon the organs of taste and in part also upon the nervous system. Coffee, tea and chocolate are prepared as infusions or decoctions of the familiar vegetables. They contain respectively an active constituent, caffein or thein (C 8 H 10 N 4 O 2 + H 2 O trimethylxanthin) or the closely related theobromin (C 7 H 8 N 4 O 2 dimethylxanthin) , which are classi- fied among the alkaloids, or vegetable bases. These have recently been prepared artificially from xanthin. These alkaloids and similar bodies in many other plants are present in the plants preformed. Their behavior is similar to that of ammonia. They have an alkaline reaction and with acids form crystalline, well-defined salts. All of these vegetable bases affect the nervous system, some feebly, as the preceding, or more actively stimulating, as quinin; others have a more powerful stimulating effect, to the point of paralysis, including active poisons, such as morphin, atropin, strychnin, curarin, nicotin, etc. The alkaloids of coffee, tea and chocolate confer upon the infusions of these substances generally used as popular beverages the pleasantly stimulating effect upon the nervous system, refreshing the mind, animating movement and stimu- CONDIMENTS. 429 lating to increased activity. In this respect they resemble the stimulating extractives of beef-broth. Coffee contains about per cent, of caffein, which is partially first set free in the process of roasting. Tea contains 6 per cent, of thein, green tea also i per cent, of ethereal oil, black tea \ per cent.; green tea 1 8 per cent., black tea 15 per cent, of tannic acid. Green tea yields on the whole about 46 per cent., black tea scarcely 30 per cent., of extract. In addition the inorganic substances in these beverages are to be considered, Tea contains 3.03 per cent, of salts, including considerable amounts of soluble compound of iron and manganese, which are important in the formation of hemoglobin! , and also sodium-salts. In coffee, which yields 3.41 per cent, of ash, potassium preponderates. In all three beverages, however, the remaining inorganic substances that are found in the blood are present in suitable propor- tions. Cocoa is only inadequately utilized as a nutritive agent: of 50 grams only 5 grams of albumin, 16 grams of fat and 6 grams of starch. Alcoholic beverages owe their activity primarily to the alcohol they contain. With regard to the latter the following is to be noted: i. Alcohol is decomposed in the body, principally into carbon dioxid and water. In this respect it does not differ essentially from other articles of food, and it is thus to be regarded as a source of heat. As alcohol readily undergoes this combustion in the body, its use can, therefore, diminish to a certain degree the consumption of the con- stituents of the body itself. It has, however, been shown that with a mixed diet alcohol is not capable of protecting the albumin from decomposition, but solely the fat. With a mixed diet alcohol is not able to replace any of the carbo- hydrate of the food. Only from i to 2.5 per cent, of the alcohol passes over into the urine, from 5 to 6 per cent, into the breath. The odor of the breath is due, in addition, to other volatile substances in the alcoholic beverage, such as fusel-oil and others. Traces pass into the cutaneous secretions. 2. In small amounts alcohol has a stimu- lating effect, in large doses, through over- stimulation, a para- lyzant effect upon the nervous system. By means of this stimu- lating effect it is therefore capable of spurring the body temporarily to greater functional activity for achievement, at the expense, it is true, of a subsequent depression. 3. When taken in small suitable doses before or after meals, it aids the digestion, while larger doses interfere with digestion. 4. It diminishes the sensation of hunger. 5. It induces more active respiratory movements, and stimulates the heart and the vascular system, and thus accelerates the circulation of bright-red blood, so that muscles and nerves become more capable of action. It also causes a subjective sensation of heat. In a larger dose, however, it paralyzes the vessels by overstimulation and they become dilated, for example, in the external integument. As a result heat is radiated in greater degree through the skin than it is generated in the body, and therefore the bodily temperature is lowered. Large doses also diminish the activity of the heart by the excitation of smaller, weaker and more rapid beats. In ele- vated regions the power of alcohol is greatly enfeebled, as, on account of the low atmospheric pressure, the alcohol is rapidly given off from the blood. From the foregoing remarks it is clear that alcohol, when taken in small amounts, can be of incalculable benefit in conditions of temporary privation and want of food, in conjunction with which resistance to fatigue and an extraordinary amount of work are yet required. In a similar manner it is capable of protecting the tissues of the sick from too rapid consumption, with the exception of the al- bumin. When taken habitually, however, and especially in large amounts, it causes derangement of the nervous system by overstimulation, and undermines the forces of mind and body, partly in consequence of its poisonous properties, chiefly due to its volatile constituents (fusel-oil) , affecting the nervous system permanently, partly through its direct action in causing injurious catarrhal and inflammatory conditions in the digestive organs, and partly finally through inter- ference with and impairment of the normal metabolism. Alcoholic beverages are prepared by fermentation of the sugar obtained from FIG. 140. i, Isolated yeast-cells; 2, 3, formation of buds; 4, 5, endogenous cell-formation: 6, germination and bud-formation. 43 METABOLIC EQUILIBRIUM. various carbohydrates, especially starch. Alcoholic fermentation is a result of the vital activity of a low order of fungus, namely the yeast-fungus the sac- charomyces cerevisiae (in the fermentation of beer) and the saccharomyces ellip- soideus (in the fermentation of wine), the fungus removing directly from the saccaharine mixture the substances necessary for its existence, namely carbo- hydrates, albuminates and salts, chiefly calcium phosphate, potassium phosphate and magnesium sulphate and causing their decomposition into alcohol and car- bon dioxid, together with some glycerin (from 3.2 to 3.6 per cent.) and succinic acid (from 0.6 to 0.7 per cent.)- The yeast-liquor alone, in the absence of yeast- cells, also causes fermentation, through the presence of a ferment known as zymase, which acts like a chemical agent. Yeast belongs to the budding fungi, which multiply both by budding and by sporulation (ascospores) . It is added directly to the fluids to be fermented, or its spores, which constantly float about in the air, fall into the uncovered mixture. Perfect exclusion of yeast-cells, or their destruc- tion, as by boiling the syrup in sealed vessels, therefore, prevents the occurrence of fermentation. Alcoholic fermentation is, therefore, a result of the vital activity of a lower form of organism. Wine contains on an average from 89 to 90 per cent, of water, from 7 to 8 per cent, of alcohol, together with the ethyl-alcohol, propyl-alcohol and butyl- alcohol. The color of red wine is derived from the skins during fermentation. If the skins be previously removed red grapes will yield whitish wine. The fine taste (flower, bouquet) develops during the storing of the wine. Enanthic ether is said to give rise to the characteristic odor of wine. The value of wine depends upon the as yet unknown stimulating, volatile substances that confer upon each wine its special character. Of great importance are, further, the salts, which in their composition resemble those of the blood. Beer contains from 75 to 95 per cent, of water, alcohol from 2 to 5 per cent, (porter and ale as much as 8 per cent.), carbon dioxid from o.i to 0.8 per cent., sugar from 2 to 8 per cent., gum, dextrin from 2 to 10 per cent., cholin, the con- stituents of hops, some residue of protein-substances (gluten), fat, lactic acid, ammonia-compounds, the salts of barley and of hops. In the ash the enormous amount of phosphoric acid and potassium carbon- ate, so important in the formation of blood, is noteworthy; one hundred parts of ash contain of potassium carbonate 40.8, phosphorus 20, magnesium phosphate 20, calcium phosphate 2.6, silica 16.6 per cent. The favorable influence of beer on the formation of blood, muscles and other tissues is due to the abundance of phosphoric acid and potassium carbonate. The obesity of the beer-drinker de- pends chiefly on the fat-sparing action of the alcohol. The potassium carbonate present in beer has a fatiguing effect after heavy drinking. Spices are not consumed because of their nutritive value, but in part on account of their taste, in part because of their stimulating effect, through which they arouse the digestive organs to increased activity. In a certain sense sodium chlorid must also be regarded as a spice, being withheld at present apparently from only a few savage tribes. A similar fact was recorded by Homer. Also certain as yet unknown substances that have a marked effect on the organs of taste, and that develop only in the course of preparation of some dishes, as in the crust of a roast, and in the crust of pastry, may be included among spices. PHENOMENA AND LAWS OF METABOLISM. METABOLIC EQUILIBRIUM. By metabolic equilibrium is understood that normal condition in which precisely the same amount of material for the maintenance and growth of the organism is taken up and assimilated from the digested nourishment as is removed from the body through the excretory organs in the form of waste-materials or end-products of retrogressive tissue- metamorphosis. The income must always balance the expenditure. During the period of growth of the body a certain excess of formative activity corresponding to the increase in size of the body must pre- dominate. Thus, growing portions of the body exhibit from 2.5 to 6.3 METABOLIC EQUILIBRIUM. 431 times as active a metabolism as parts of the body already formed. On the other hand, in the years of senile debility a certain excess of bodily expenditure is to be considered as a normal phenomenon. Method. The normal metabolic equilibrium in the organism may be recog- nized: i. By determining chemically that the sum of all the egesta, given off by the body within a certain period of investigation, corresponds to the sum of the ingesta furnished by the food. In this connection the amount of carbon, nitrogen, hydrogen, oxygen, and salts, together with the water of the food and the oxygen of the inspired air, must be equal to the carbon, nitrogen, hydrogen, oxygen, the salts and the water in the excretions (urine, feces, expired air, evaporated water) of the organism. 2. The physiological equilibrium of metabolism may further be recognized in a purely empirical way from the fact that with a suitably selected diet, the body performing its ordinary functions is able to maintain its normal weight. Thus, this simple procedure of weighing makes it possible for the phy- sician to inform himself quickly and with certainty concerning the metabolism of his patient or convalescent. The tedious method of elementary metabolic analysis was first successfully undertaken particularly by the Munich investi- gators, v. Bischoff, v. Voit, v. Pettenkofer and others. It was soon apparent that of all the elements the greatest importance was to be assigned to the passage through the body of carbon and nitrogen. The total amount of carbon taken with the food (which is ascertained by elementary analysis of a sample of each article of diet, or is calculated from re- liable analyses of the articles of food) must, in complete metabolic equilibrium, correspond to the carbon in the carbon dioxid contained in the expired air (90 per cent.) from the lungs and the skin. To this there should also be added the relatively small amount of carbon in the organic excrementitious matters of the urine and the feces (10 per cent.), which is to be determined by ele- mentary analysis. As all organic food and all the constituents of the body contain carbon, an increased loss of carbon (as compared with the income) in- dicates that organic matter in excess is being decomposed in the body; on the other hand, diminished excretion of carbon necessarily indicates an ad- dition to the substance of the body. For the exact determination of the car- bon dioxid in the expired air the Munich investigators employed v. Petten- kofer's respiratory apparatus. With regard to the nitrogen, which should be determined in the ingesta as well as the excreta by the method of Kjeldahl, it was found that almost all the nitrogen of the ingested food is excreted again in the urine within 24 hours, principally in the form of urea. The remaining nitrogenous urinary constituents (uric acid, kreatinin, etc.) furnish only about 2 per cent, of the nitrogenous elimination. In addition, the nitrogen-content of the feces is to be taken into account (from 4 to 5 per cent, in dogs). A small amount of nitrogen also escapes from the organism in the expired air; also a portion with the desquamated epidermal structures (about 50 mg. of hair and nails daily) and in the sweat. The opinion that practically all the nitrogen ingested with the food is excreted in the urine and the feces was established for carnivora by v. Voit and Gruber; for ruminants by Henneberg, Stohmann and Grouven, and for man by Ranke. Contrary to this view a number of the older as well as more recent investigators have made the assertion that the total amount of nitrogen cannot be recovered from the excretions mentioned, but that an appreciable nitrogen-deficit exists. According to Leo about 0.55 per cent, of the albumin decomposed in the body yields its nitrogen (which may be assumed to amount to 15 per cent.) in the gaseous state. In making exact analyses of metabolism this gaseous excretion of nitrogen must naturally be taken into account. In the food nitrogen occurs almost exclusively as a constituent of albu- minous substances. In the excretions it indicates decomposition of 'the albuminous constituents of the body. As proteids contain on the average 1 6 per cent, of nitrogen the amount of albumin corresponding to the amount of nitrogen excreted is determined by multiplying the latter figure by 6.25. Nitrogenous equilibrium thus indicates that the albuminous substances in the body are unchanged. If nitrogen is retained gain in weight takes place, principally in the form of muscle ; if there is an excess of nitrogenous excre- tion, consumption of the albuminous constituents of the body must ensue. 432 METABOLIC EQUILIBRIUM. The relative amount of nitrogen and carbon in albumin may be expressed as i : 3.3. Of the amount of carbon decomposed in the process of metabolism there are 3.3 parts for every part of nitrogen in the proteids subjected to the process. The excess is to be attributed to the decomposition of non-nitrogenous substances (fats or carbohydrates). It is believed that the greater portion of the 'proteids are decomposed in the tissues into carbamic acid, which is then transformed in large amounts, in the liver, into urea. The excretion of nitrogen after the taking of food is, in animals, not uniform from hour to hour, but it increases rapidly at once, reaches its maxi- mum after 5 or 6 hours and then gradually declines. The excretion of sulphur and phosphorus pursues a similar course, though the maximum excretion, on a meat diet, occurs as early as the fourth hour. On addition of fat to a meat- diet the excretion of nitrogen and of sulphur is more evenly distributed through- out the hours of the day. In human beings Rosemann found during the day an increase between 9 and n a. m., as a result of breakfast and the stimu- lation of all of the functions in the morning; a second increase between 3 and 4 p. m., as a result of dinner; a third, smaller one between 7 and 9 p. m., fol- lowing supper; and a final increase between 9 and n p. m. The excretion diminishes during the night. The nitrogenous constituents of the body become poorer in carbon as a result of the processes of metabolism, but richer in nitrogen and oxygen ; for there are, in the albumins, 4 atoms of carbon for each atom of nitrogen, in gelatin 3^ atoms of carbon, in glycocoll 2 of carbon, in kreatin i^ of carbon, in uric acid i of carbon, in allantoin i of carbon, in urea, finally, only \ atom of carbon. The oxygen furnished by respiration is either determined directly from the reduction in its amount in the air supplied to the animal, or it is calculated from other data. This inspired oxygen, as well as the oxygen of the food, makes its appearance principally in the form of carbon dioxid and water; a small amount leaves the body in the excrementitious products. The amount of oxygen absorbed in respiration is the measure of the entire process of combustion in the body, by which carbon is oxidized into carbon dioxid and hydrogen into water. The respiratory quotient indicates the amount of inspired oxygen that is required alone for the combustion of the carbon. If the volume of carbon dioxid produced by the combustion of pure carbon is exactly the same as the volume of oxygen consumed for this purpose, the respiratory quotient is i. This is the case in the decomposition of carbo- hydrates. As hydrogen and oxygen are present in these compounds in the proportion necessary to form water by combustion, practically all the oxygen is utilized for the oxidation of the carbon of the carbohydrates. For albumin the respiratory quotient is 0.8, for, on a purely albuminous diet, only 800 cu. cm. of carbon dioxid are excreted for every 1000 cu. cm. of oxygen. For fats the respiratory quotient is 0.7, for, on a diet of fat, only 700 cu. cm. of carbon dioxid are excreted for every 1000 cu. cm. of oxygen consumed. Thus for fats and albumin the respiratory quotient is smaller than for carbohydrates, the volume of carbon dioxid excreted is less than that of oxygen inspired, because in the combustion of albumin or fat a part of the oxygen taken up must be employed for the oxidation of hydrogen into water. In case a larger volume of carbon dioxid is excreted than the amount of oxygen absorbed, the respiratory quotient rises above i. This happens if, in addition to the inspired oxygen, a portion of the oxygen from the con- stituents of the food is converted into carbon dioxid in the process of com- bustion in the body. This is the case, for example, when nutritive materials rich in oxygen (for example, carbohydrates) are transformed in the body into those poor in oxygen (for example, fats). The respiratory quotient may also, under certain circumstances, become even smaller than it is after an exclusive fat-diet, if, for instance, a portion of the inspired oxygen is employed in the body for the formation and deposi- tion in the tissues of compounds rich in oxygen (for example, in the formation of glycogen) . ^ The respiratory quotient may, however, exhibit certain periodic varia- tions independently of the character of the diet. As the oxygen taken up is not always used in the formation of carbon dioxid immediately upon its entrance into the body, but as certain intermediate predecessors of carbon dioxid, rich in oxygen, may accumulate in the body and be excreted only NOURISHMENT FOR A HEALTHY ADULT. 433 later completely oxidized into carbon dioxid, it may happen that during one part of a period of dieting more oxygen may be taken up than is given off as carbon dioxid. Hydrogen leaves the body principally oxidized into water, but it may also leave the body combined with organic excreta. The water is given off with the urine, the feces, through the lungs and by evaporation from the skin. As hydrogen is oxidized into water the amount of water given off is naturally greater than that taken up. The salts are excreted in various ways, the most soluble of them passing out with the urine, a few, particularly potassium-salts, and those that are soluble with difficulty, with the feces, and some, like com- mon salt, in part also with the sweat. The salts contained in the ingesta and excreta are estimated by weight after incineration. If the sulphur and the phosphorus are to be estimated separately the amount of each in the ingested food is oxidized by combustion, by addition of sodium hydroxid and potassium nitrate into sulphuric and phosphoric acids respectively. The same method is followed for their estimation in the feces, as well as for sulphur in the epidermal structures. The sulphuric and phosphoric acids so obtained, as well also as the sulphur and the phosphorus excreted in the urine in an already oxidized form, are estimated according to the method described on p. 491. The sulphur is derived principally from the albuminous food; about half of it is excreted with the urine as sulphuric acid, half with the feces (as taurin) and through the epidermal structures. For every body, there is, according to its weight and activity, a minimum and a maximum limit of metabolic balance. If less food is supplied than is necessary for the first, loss of body- weight results. If, on the other hand, an excess of food is supplied, any amount exceeding the maximum limit will be passed unabsorbed as superfluous ballast with the feces, provided it cannot be utilized for increase of flesh. The more the body gains in weight on a generous diet, the higher the mini- mum limit rises. With marked increase of flesh, therefore, the necessary supply of food must be relatively much greater than in the case of thin persons, in order to cause a like increase in the tissues of the body. With continued increase in flesh there finally results a condition in which the digestive organs are able to prepare only sufficient material for the maintenance, but not for increase, of weight. QUALITY AND QUANTITY OF NOURISHMENT FOR A HEALTHY ADULT. The question as to the substances that are needed by man for his satisfactory nourishment, and the amount required, has naturally been answered in a purely empirical way by observation of the manner of nourishment of healthy individuals at different ages and with varying degrees of activity. As, for example, the infant flourishes and grows on a diet of milk, milk must undoubtedly include in its composition nutrient matter qualitatively and quantitatively appropriate. In accordance with his entire organization man beldngs to the omnivora, that is, to the class of beings that is adapted to a mixed diet. He possesses the canine tooth of the carnivora, but his intestine is shorter than that of the herbivora. For his continued existence man requires the following four principal nutritive substances, none of which can be spared from the diet for any length of time : i. Water; for an adult from 2700 to 2800 grams daily in food and drink. Withdrawal of water increases the disintegration principally of the albu- minous tissues. If thirsting cats are kept for a long time in hot air, a con- centration of the blood becomes manifest, which, through chemical injury, leads to a fatal central narcosis by poisoning of the vital centers. 28 434 NOURISHMENT FOR A HEALTHY ADULT. 2. Inorganic matters as integral parts of all of the tissues, without which their structure could not be formed. These substances are present in sufficient amount in all the usual articles of diet, so that it is unneces- sary to supply them separately (as the nutrition of animals shows). Increase in the supply of salt causes increase in the consumption of water, and this in turn causes increase of nitrogenous decomposition in the body. Withdrawal of certain necessary salts causes disturbances in the nutrition of the tissues containing them. Thus, the use of food free from calcium is followed by disturbance in normal bone-formation ; withholding common salt causes albuminuria. The body absorbs the iron required for the formation of blood in part in the form of complex organic compounds from the vegetable and animal kingdoms, but in part also in an inorganic form; phosphorus principally from proteids containing phosphorus. The alkaline salts derived from vegetable food serve to neutralize the sulphuric acid formed by oxidation of the sulphur of the proteids. Food that has been artificially deprived of all salts causes rapid death in animals by acid intoxication. Only as a matter of necessity does man occasionally resort to the use of considerable amounts of inorganic matter in order to obtain the organic nutrient material mixed with it, as A. v. Humboldt relates of the inhabitants along the shores of the Orinoco and the Meta, and who, in times of scarcity, when the catch of fish is low, are compelled to eat a certain kind of rich clay, containing an abundance of infusoria. 3. At least one animal or vegetable proteid. The albuminates are utilized to replace the consumed nitrogenous tissues, particularly the muscles. In addition, they are used as sources of energy and heat. The latter function of albuminous food can be fulfilled by non-nitrogenous food; the first, however, can not. The albuminates contain from 15 to 1 8 per cent, of nitrogen. Different tissues of the body contain proteids in the following proportions: Blood 20.56 per cent., muscles 19.9 per cent., liver 11.74 per cent., brain 8.63 per cent., blood-plasma 9.0 per cent., milk 3.8 per cent., lymph 2.4 per cent. According to Pfluger and Bohland a growing youth weighing 62 kilos decom- poses 89.9 grams of albumin daily. It is a remarkable fact that asparagin a nitrogenous amido-body, which is formed in sprouting plants from albumin and under certain circumstances may be again transformed into this in the plant combined with gelatin is capable of replacing the albumin of the food. Asparagin alone is capable (only in herbivora) of diminishing the decomposition of albumin. Salts of ammonia, glycocoll, sarcosin and benzamid increase the destruction of proteid. 4. At least one form of fat or digestible carbohydrate. These serve principally for the replacement of the decomposed fat and non-nitrog- enous constituents of the body. On account of the large amount of carbon they contain, they are, through their oxidation, the chief sources of heat-production. Fats and carbohydrates can replace each other in the diet in reciprocal amounts corresponding to the quantity of heat that they are able to produce by their combustion in the body. In the same way, the portion of the albumin of the food that does not serve for the restoration of the tissues can be replaced by equivalent amounts of fat or carbohydrates. In this connection 100 parts of fat are equivalent to 256 of grape-sugar, 243 of milk-sugar, 234 of cane- sugar, 221 of dry starch. In general the same amounts correspond to 227 parts of carbohydrate, as well as to 227 of albumin. NOURISHMENT FOR A HEALTHY ADULT. 435 The compound sugars in the organism must first be decomposed into monosaccharids before they are oxidized, just as they are decomposed into monosaccharids in the process of fermentation. If the organism is unable to split a compound sugar into its components, it cannot oxidize the sugar. This splitting, for example, of cane-sugar and milk-sugar, is carried out in the intestine. If these substances are introduced subcutaneously they are not split up, and therefore are not made use of; that is, they are excreted again in the urine. It is a remarkable fact that butter can be injected subcutaneously in considerable amounts and, thus introduced, is utilized either for combustion or for the deposition of fat. With regard to the relative proportions in which these various nutri- tive materials should be combined, experience has taught that for man, a diet in which the nitrogenous and non-nitrogenous elements are mixed in the proportion of one nitrogenous to 3^, or at the most 4^, parts of the non-nitrogenous elements, must be considered as the most advantageous. If the customary articles of diet be considered according to this standard, it can easily be seen to what degree they conform with the requirement mentioned, and, furthermore, that a suitable diet may often be formed by a mixture of several of them. The following table shows the proportion of nitrogenous and non- nitrogenous matters in various articles of food : Nitrog- Non-nitrog- enous. 1. Veal, 10 2. Hare, 10 3. Beef, 10 4. Lentils, 10 5. Beans, 10 6. Peas, 10 7. Mutton (fattened), 10 8. Pork 10 9. Cow's milk, 10 to enous. I 2 21 22 23 27 Nitrog- Non-nitrog- enous. enous. TO. Human milk, ..... 10 to 37 11. Wheat-flour, ..... 10 46 12. Oat-meal, ....... 10 50 13. Rye-flour, ....... 10 57 14. Barley-flour, ..... 10 57 15. White potatoes,. . . 10 86 16. Blue potatoes, . . . . 10 115 17. Rice , ............ 10 123 1 8. Buckwheat-flour, .. 10 130 This survey shows that in addition to human milk, wheat-flour lies within the normal limits with regard to its proportional composition. On the other hand the articles of diet from i to 9 require an addition of non-nitrogenous, those from 12 to 1 8 of nitrogenous, substances in order to maintain the proportions from 10:35 to 10 : 45. A man who attempted to live on meat alone would, there- fore, be just as irrational as one who took potatoes alone as food. Experience long ago impressed upon the mind of the people the fact that milk and eggs will indeed support life, but that a meal of meat requires potatoes or bread; a dish of beans a portion of bacon. It should also be especially mentioned that the proportions of the diet vary in accordance with climate and season. As with a considerable degree of cold the organism must produce more heat, the inhabitants of higher latitudes take relatively more non-nitrogenous food (fat and sugar or starches) , which, on account of its richness in carbon, is especially suited for the generation of heat in the body. The graphic representation of the composition of the most important articles of food in Fig. 141 (after A. Fick) is especially clear. If it be borne in mind that the nitrogenous bodies in the food must be in the proportion of i : 3$ to 4^ of the non-nitrogenous, a glance will show at once what articles of diet are suited for food without addi- tion, as well as which of them may be suitably combined to supplement one another. The absolute amount of food that an adult needs during twenty-four hours is influenced by various factors. As food represents the reservoir 436 NOURISHMENT FOR A HEALTHY ADULT. of chemical potential energy from which the body generates on the one hand heat and on the other kinetic energy, the absolute amount of food Explanation of the figures: Water. Proteids. ANIMAL FOOD. Albuminoids. Non-nitrogenous organic matter. Human milk 89 VEGETABLE FOOD. Explanation of the figures: Salts. Potatoes White tur- nips Water. Proteids. Digestible Undigestible Non-nitrogenous organic matter. 75 90,5 Salts. 0-5 Cauliflower Beer 80 90 FIG. 141. must be increased when the loss of heat from the body (winter) or its muscular activity (work) increases. On the average a man requires 130 grams of proteids, 84 grams of fat, and 404 grams of carbohydrates. NOURISHMENT FOR A HEALTHY ADULT. 437 The following figures are average values derived from many individual ob- servations : An adult requires in 24 hours: Resting Moderate Work Hard Work (v. Pettenkofer Air.ount of Food in Grams. (Playfair). (Moleschott). (Playfair). and v. Voit.) Proteids, 70-87 130 155.92 137 Fats, 28.35 84 70.87 117 Carbohydrates (sugar, starch, etc.) , 310.20 404 567.50 352 In an analogous example taken from C. v. Vierordt the elementary matters in the food will be estimated and at the same time the amounts ingested be com- pared with those excreted. An adult with moderate activity consumes: C H N O 120 grams of albumin, containing, 64.18 8.60 18.88 28.34 90 grams of fats, 70.20 10.26 9-54 330 grams of starch, 146.82 20.33 162.85 281.20 39.19 18.88 200.73 In addition: 744.11 grams of oxygen from the air by respiration. 2818 grams of water. 32 grams of inorganic compounds (salts). The whole amounts to about 3.2 kg. or about ^ of the body-weight. Over 6 per cent, of the water, about 6 per cent, of the fat, "about i per cent, of the albu- min and about 0.4 per cent, of the salts in the body are thus daily replaced. An adult with moderate activity excretes : Water C H N O With respiration, 330 248.8 . . ? 651.15 By transpiration, 660 2.6 . . . . 7.2 In the urine, 1700 9.8 3.3 15.8 n.i In the feces, 128 20.0 3.0 3.0 12.0 2818 281.2 6.3 18.8 681.45 In addition 296 grams of water not included in the 2818 grams of water in- gested are formed in the body by oxidation of the hydrogen of the food. These 296 grams of water contain 34.89 grams of hydrogen and 263.31 grams of oxygen. Further, 26 grams of salts are passed with the urine and 2 grams with the feces. An adult at rest consumes during twenty-four hours 96.5 grams of proteid equivalent to 1.46 grams for each kilogram; at hard work, 107.6 grams equivalent to 1.6 grams for each kilogram. Three or four times as much fat as albumin is transformed daily. Investigations, principally by the Munich school, have determined the fol- lowing minimum figures for the diet at various ages: Age. Nitrogenous. Fat. Carbohydrate. For a child up to i years, 20-36 gms. 30-45 gms. 60-90 gms. 250400 500 400 350 260 For a child from 6 to 15 years, 70-80 27-50 For a man, with moderate activity, 1 18 56 For a woman, with moderate activity, ... 92 44 For an old man 100 68 For an old woman, 80 50 It is frequently asserted that, in case of necessity, a considerably smaller amount of proteid (55 gms. for a man) would suffice, providing that the amount of food were sufficient to supply the requisite number of calories for the body, that is, 45,000 calories for each kilogram of body- weight. The diet of the Japanese contains, for example, a much smaller amount of nitrogen than that of the Euro- pean. Numerous experiments have demonstrated, however, that an adult weighing 70 kilograms can be sufficiently nourished only temporarily, and not for any length of time, on less than 80 grams of proteid. 438 NOURISHMENT FOR A HEALTHY ADULT. The minimum amount of proteid requisite for preserving the nutrition must be so large that the nitrogen it contains will be equal to the nitrogen excreted by the individual in question in a fasting condition. Small animals consume for each unit of body-weight decidedly more than large ones. This depends not so much on the fact, as was formerly believed, that the metabolism is more active in small animals, as on the fact that small animals, in proportion to their body-weight, possess a larger body-surface, and are, therefore, more exposed relatively to external influences, and especially to the cooling effect of the surrounding air. If the amount of the substances de- composed is compared, not to the body- weight but to the body-surface, for example to one square meter, almost the same values will be obtained for small is for large animals of the same species. On the other hand, the values for animals of different species are different. The absolute amount of food that an adult requires in twenty-four hours is most conveniently expressed in the form of units of energy that it is capable of supplying, that is, in calories. An adult, with a moderate amount of fat, requires daily, for each kilogram of body- weight : At complete rest from 32,000 to 38,000 calories. At light work 35,ooo " 45,000 At hard work 50,000 " 70,000 Therefore, a man weighing 70 kilograms at light work would require in the neighborhood of 70 X 40,000, or 2,800,000 calories. Any diet containing 2,800,000 calories is sufficient; but the diet must always contain proteid and in no event less than 80 grams daily. As i gram of proteid yields 4100 calories, i gram of carbohydrate 4100 calories and i gram of fat 9300 calories, the following dietetic combina- tions may be considered as sufficient: Grams. Calories. 80 of proteid = 328,000 300 of carbohydrate .... = 1,230,000 113 of fat = 1,237,000 2,795,000 80 of proteid = 328,000 265 of fat = 2,465,000 100 of proteid 280 of carbohydrate 133 of fat 2,793,000 = 410,000 = 1,148,000 = 1,237,000 2,795,000 Grams. Calories. 80 of proteid = 328,000 200 of carbohydrate .... = 820,000 177 of fat = 1,646,000 2,794,000 328,000 1,640,000 828,000 80 of proteid 400 of carbohydrate . . . 89 of fat For a short time also: 60 of proteid 320 of carbohydrate . 133 of fat 2,796,000 246,000 1,212,000 1,237,000 2,795,000 In most of the ordinary articles of food nitrogenous and non-nitrog- enous substances occur together, but, as the statements on page 435 show, in widely different proportions. Man requires a diet in which the proportion between nitrogenous and non-nitrogenous substances is between 1:3^ and i : 4^. If a person takes food in which this propor- tion does not hold, he must consume an excessive amount of it, in order to obtain a sufficient quantity of that substance in which the article of diet is relatively deficient. This, it is clear, must necessarily cause waste of the preponderating substance. Moleschott has, in this con- nection, grouped the principal articles of diet together. In order to METABOLISM IN THE STATE OF STARVATION 439 obtain the necessary 130 grams of proteid a laborer must consume the following amounts of various foods : Cheese 388 gms. Beef 614 gins. Rice 2562 gms. Lentils 491 Eggs 968 Rye-bread... 2875 " Peas .582 Wheat-bread. . 1444 Potatoes 10000 " It is quite evident that, in using the last-named substances, the laborer must consume a useless excess of non-nitrogenous food. In order to obtain from his food the necessary 448 grams of carbohydrate (or the equivalent amount of fat) required for his subsistence, such a laborer would have to eat : Rice 572 gms. Peas 819 gms. Cheese 2011 gms. Wheat-bread. . .625 Eggs 902 Potatoes 2039 " Lentils 806 Rye-bread 930 Meat 2261 " Thus, particularly with the exclusive use of cheese or meat, the laborer would be compelled to consume enormous quantities, which would be equivalent to a waste of nitrogenous material. Finally, attention should be drawn to the fact that not all of the food is digested or absorbed in the digestive tract, but that there is always a certain residue that is unutilized and is voided with the feces. Calculated as dry substance this amounts in percentages: in rice to 4.1, in white bread to 4.5, in meat to 5.2, in eggs to 5.2, in milk to 9, in potatoes to 9.4, in peas to n.8, in beans to 18.3, in black bread to 15. It is more advantageous to administer the amount of food required daily in several portions than to give it at infrequent intervals or all at once ; the distribution of the food over several meals diminishes proteid decomposition. For the herbivora a diet suffices containing one part of nitrogenous to eight or nine parts of non-nitrogenous material. METABOLISM IN THE STATE OF STARVATION. If a warm-blooded animal is deprived of all food, it must, naturally, decompose and utilize the energy stored in its own tissues in order to generate its bodily heat and to perform any mechanical labor demanded of it. Its body- weight, accordingly, steadily decreases till death from starvation occurs, the tissues and organs meanwhile becoming richer in water. Method. For an exact investigation of the state of inanition (i) the starving man or animal is weighed daily. (2) All of the carbon and nitrogen in the expired air, the urine and the feces is estimated daily. The nitrogen found can be derived only from the consumed proteids of the body, especially the muscles, and from the same source also a varying amount of carbon, in accordance with the composition of the muscles. The amount of carbon remaining after subtracting this amount is to be attributed to the decomposition of the non-nitrogenous tissues of the body, principally the fat. After the amount of muscle and fat broken down has been thus computed, the subtraction of this amount from the total loss of body- weight will yield the amount of water lost. The following example, which deals with a cat starved to death by Bidder and Schmidt, shows the various excretions on the successive days of starvation: 44 METABOLISM IN THE STATE OF STARVATION. DAY. BODY- WEIGHT. AMOUNT OF WATER TAKEN. AMOUNT OF URINE. UREA. INORGANIC CONSTITU- ENTS OF THE URINE. DRY FECES. EXPIRED CARBON. WATER IN URINE AND FECES. i .... 2464 98 7-9 J -3 1.2 13-9 91.4 2 .... 2297 n-5 54 5-3 0.8 1.2 12.9 50-5 3 .... 2210 45 4.2 0.7 I.I 13 42.9 4 .... 2172 68.2 45 3-8 0.7 I.I 12.3 43 5 .... 2129 55 4-7 0.7 i-7 II.9 54-1 6 2O24 44 4-3 0.6 0.6 ii. 6 41.1 7 .... 1946 40 3-8 o-5 0.7 ii 37-5 8 .... 1873 42 3-9 0.6 i.i 10.6 40 9 1782 !5- 2 42 4 o-5 !-7 10.6 41.4 10 .... 1717 35 3-3 0.4 !-3 10.5 34 ii .... 1695 4 3 2 2.9 o-5 I.I IO.2 3-9 12 .... 1634 22.5 30 2.7 0.4 I.I 19-3 29.6 I 3 !57o 7- 1 40 3-4 -5 0.4 IO.I 36.6 I 4 1518 3 4i 3-4 -5 o-3 9-7 38 15 1434 4i 2.9 0.4 o-3 9-4 38.4 16 1389 48 3 0.4 O.2 8.8 45-5 17 J 335 28 1.6 0.2 -3 7-8 26.6 i8f ... 1267 13 0.7 O.I 0.3 6.1 12.9 -1197 i3i-5 775 6 5-9 9.8 15.8 190.8 734-4 The cat before death had lost 1197 grams in weight. This loss may be dis- tributed, according to what has been said, as follows: Proteid 204.43 grams, or 17.01 per cent.; fat 132.75 grams, or 11.05 P er cent.; water 863.82 grams, or 7 1.91 per cent, of the total loss of weight. With regard to the general phenomena of inanition it is worthy of remark that strong, well-nourished dogs die of starvation only after four weeks, while man succumbs in twenty-one or twenty-two days. Six persons suffering from melancholia, who had taken water, lived for forty-one days, however. In recent years voluntary exhibitions of starvation have become the fashion. The most striking of these was given by the Italian painter, Merlatti, who, it is alleged, withstood starvation for a period of fifty days with the use of water only. Succi, according to unexceptionable testimony, fasted for thirty days. Under such" conditions the regulation of temperature, the circulation, the respiration, the muscular and the nervous activity were found to be within limits of normal variation; the secretions necessary for digestion were, on the other hand, almost abolished. Small mammals and birds succumb within nine days, but frogs only after nine months. Full-grown, vigorous mammals, on the contrary, have lost as much as T ^ of their weight (from i to |) before death. In man the decrease in weight is relatively greatest during the first few days. Young individuals die much earlier than adults. To outward appearance the emaciation is striking. The mouth is dry, the walls of the alimentary tract become remarkably thin, the digestive juices are no longer secreted, the action of the heart is enfeebled, the pulse, smaller and of lower tension, is less frequent, the respirations are increased in fre- quency and more superficial, the urine is highly acid on account of increase in sulphuric and phosphoric acids, and its chlorin-compounds soon disappear almost entirely. The blood is poorer in water, the plasma in albumin; the gall-bladder is greatly distended, a fact that points to uninterrupted destruction of red blood- cells in the liver. The liver is small and extremely dark. The muscles tire readily. Finally, great weakness of the wasted and friable muscles develops and death follows amid signs of the greatest prostration and coma. The conditions of metabolism are apparent from the foregoing table, accord- ing to which the decrease in the excretion of urea is much greater than that of carbon dioxid. From this it may be concluded that a correspondingly greater breaking-down of fats than of proteids takes place. According to the calculations a tolerably constant amount of fat is broken down daily, while the proteids undergo much slighter destruction with the progress of the days of fasting. Drinking of water hastens the destruction of the proteids. METABOLISM IN THE STATE OF STARVATION. 441 In the case of the fasting virtuoso, Cetti, Zunty and Lehmann found that the consumption of oxygen and the production of carbon dioxid, as calculated for the unit of body- weight, rapidly reach minimal values, below which they did not fall with continued starvation. On the average, the consumption of oxygen from the third to the sixth day of fasting amounted to 4.65 cu. cm. for each kilo- gram of body- weight and for each minute. Absolutely, as regards the individual, the respiratory interchange decreased slowly, but this decrease failed to keep pace with the decrease in the weight of the body. At the beginning of starvation the amount of carbon dioxid diminished more than the consumption of oxygen. The respiratory quotient was 0.67. The urea from the first to the tenth day of starvation decreased from 29 to 20 grams. In the case of another faster, Succi, Luciani found that a nitrogenous excretion of 16.23 grams had decreased on the first day of fasting to 13.8 grams, on the seventeenth day to 7.8 grams, on the twenty-second to 4-75 grams, on the twenty- eighth day to 5.6 grams. Also Johannson, Landgren, Sonden and Tigerstedt found that metabolic activity at first declined quickly and to a large degree, later slowly and slightly. A consideration of the relative loss of weight of the various organs is also of great interest, as shown by comparison with a similar animal killed without preliminary starvation. It should be stated, however, in this connection, that many organs lose weight proportionately, for example, the bones (and as a result phosphoric acid, calcium, and magnesium increase in the urine), while other parts exhibit a disproportionately marked decomposition, for example the fat. The latter are broken down with especial rapidity and from them other organs are in part nourished during starvation. Finally, certain organs, like the heart and the nerves, suffer slight loss, as they are able to maintain themselves on the de- composition-products of other tissues. In the breaking down of the tissues the nuclei also suffer and certain glands undergo fatty degeneration. A starved male cat lost, according to v. Voit: Percentage of the Percentage of the Amount Originally Total Loss of the Present. Body. 1. Fat 97 26.2 2. Spleen 66.7 0.6 3- Liver 53.7 4-8 4. Testicles 40.0 o.i 5. Muscles 30.5 42.2 6. Blood 27.0 3.7 7. Kidneys 25.9 0.6 8. Skin 20.6 8.8 9. Intestines 18.0 2.0 10. Lungs 17.7 0.3 n. Pancreas 17.0 o.i 12. Bones 13.9 5.4 13. Central nervous system 3.2 o.i 14. Heart 2.6 0.02 15. Remainingportions of the body together 36.8 5.0 The average resistance of the hemoglobin is increased by inanition. Allusion should be made also to an important difference between animals that have been liberally fed with meat or fat before the beginning of the period of inanition, and those that have been kept on a barely sufficient diet. Liberally fed animals suffer much greater loss in weight in the early days of starvation than in the later. Furthermore, fat individuals exhibit from the first a greater decom- position of fat in proportion to proteids than thinner individuals. Animals liber- ally fed with proteid continue to decompose much albumin in the early days of fasting. Animals fed with little proteid, on changing to a liberal albuminous diet, likewise continue to decompose only a limited quantity of albumin in the first few days. 442 METABOLISM ON A DIET OF MEAT, ALBUMIN OR GELATIN. METABOLISM WITH AN EXCLUSIVE DIET OF MEAT, ALBUMIN OR GELATIN. According to Pfliiger the higher animal (as has been demonstrated experi- mentally for the dog) can be nourished and maintained almost exclusively on proteids, without impairment of its functional activity. Proteids are, therefore, to be designated as foods of the first order, as fundamental foods. Pfliiger applies the term nutritive requirement to the smallest amount of lean meat that is capable of maintaining the metabolic equilibrium, without fat or carbohydrate of the body being utilized for decomposition. The amount of this nutritive requirement is determined by the weight of the flesh of the animal and increases with this on addition of flesh to the body. The decomposition of proteids increases also with the supply of proteid if the latter exceeds the nutritive requirement. Under such circumstances, however, a certain portion of the excess of proteid is conserved and deposited as flesh. The nutritive requirement of the dog is for i gram of animal nitrogen 0.0636 gram of nutrient nitrogen; or i kilogram of nitrogenous animal tissue requires 2.099 grams of nitrogen in the food. Human beings provided exclusively with meat free from fat are, however, not able to maintain the metabolic equilibrium. Compelled to adhere to such a diet permanently they would certainly succumb. The reason for this is obvious. In beef the proportion of nitrogenous to non-nitrogenous elementary nutritive constituents is as i to 1.7. The healthy person gives off daily in the carbon dioxid of the respiration, in the feces and in the urine, about 280 grams of carbon. If he desired to obtain these 280 grams of carbon from the carbon of an exclusively meat-diet, he would be compelled to digest and assimilate more than 2 kilos of pure meat in twenty-four hours. His organs, however, would by no means suffice to accomplish this permanently. The man would under such conditions soon be compelled to consume less meat. This result would require the decomposition of the constituents of his own body, first of all the fat and then also the proteids. Also in the following manner it can be clearly shown that a human being is unable to maintain himself on a meat-diet exclusively. A man weighing 70 kilo- grams and doing a moderate amount of work requires 40,000 calories daily for each kilo of body-weight, therefore a total of 2,800,000 calories. One thousand grams of lean beef yield 95,000 calories. Such a person would, therefore, be compelled to consume about 3 kilograms of beef, or 2,850,000 calories, daily, and this, natur- ally, is impossible. The carnivora (dog) , whose digestive organs are especially adapted to the digestion of meat, by reason of the short intestine and actively solvent in- fluence of the digestive fluids upon proteids, cannot be maintained permanently on chemically pure albumin, although this is possible with the leanest meat, which, however, always contains not less than 0.59 per cent, of fat. Under such circum- stances the animal consumes large amounts of meat, and as a result the elimina- tion of urea is increased correspondingly. If it eat still larger amounts, it may even put on flesh, and then, in accordance with the maintenance of the newly deposited flesh, it requires naturally a constantly increasing amount of meat. The herbivora are under no circumstances capable of subsisting upon a meat- diet exclusively, as their digestive apparatus, which is adapted for vegetable food, would by no means suffice for the disposal of the necessary amounts of meat. Of gelatin it has been shown that it may replace the proteids in the food, in so far as these serve as sources of energy and heat, but not if bodily tissue is to be replaced. Under such circumstances two parts of gelatin take the place of one part of proteid. The carnivora, which can maintain their metabolic equilib- rium with large amounts of meat, are capable of doing this with less meat and a corresponding addition of gelatin. According to Munk the dog is capable for a few days of replacing of its proteid requirement by gelatin. A diet of gelatin exclusively is, however, inadequate. In addition the animals soon lose their appetite for such food. In consequence of its solubility the addition of gelatin (calf's-foot jelly) to the food of convalescents has been recommended. The absorbed products of the digestion of gelatin are conveyed to the connective tissues, which constitute a re- pository for it. After a long-continued diet of chondrin, together with meat, glucose has been found in the urine. LAWS GOVERNING METABOLISM. 443 AN EXCLUSIVE DIET OF FATS OR CARBOHYDRATES. If fat alone is supplied, the body is unable to maintain itself. In consequence of the deficiency of nitrogen, the animal must necessarily perish. The symptoms occurring with this form of diet are as follows : The animal in question secretes less urea than in a state of hunger. Therefore, the consumption of fat must restrict that of the flesh of the animal itself. This is due to the fact that the fat, being a readily combustible substance, is more readily oxidized in the body than the less readily combustible nitrogenous albuminates. If the amount of fat taken is exceedingly large, not all of the carbon of the fat can be recovered in the excreta, or as carbon dioxid in the expired air. Accordingly the body must accumu- late fat, while naturally it destroys proteids in corresponding amount. The animal thus becomes fatter and at the same time poorer in flesh. The result of administration of carbohydrates alone, which must first be con- verted into sugar by the digestive processes, exhibits marked similarity to that obtained with a pure fat-diet. It should, however, be noted that the sugar in the body more readily undergoes destruction than the fat, and, further, that with reference to the nutritive value, 256 parts of glucose are the equivalent of 100 parts of fat. Accordingly, a carbohydrate-diet restricts the decomposition of proteids even more readily than a pure fat-diet. Just as it is necessary outside of the body for the fermentation of disaccharids and polysaccharids that these be first decomposed into monosaccharids, so also the combustion of sugar in the body can occur only on condition that a trans- formation into monosaccharids has previously taken place. LAWS GOVERNING METABOLISM ON A MIXED DIET OF MEAT AND FAT OR CARBOHYDRATES. If a dog in a state of metabolic equilibrium be given an amount of fat and starch exceeding its requirements, elimination through metabolism is not in- creased, but the excess of these non-nitrogenous foods administered is deposited in the body of the animal as fat. If a dog fed with the leanest possible meat, and in a state of metabolic equilib- rium, be given an additional amount of meat exceeding its requirements, the elimination through metabolism increases almost proportionately to the addi- tional amount administered beyond the requirements. Only a small portion of the addition is conserved and increases the body-weight as a deposition of flesh. This augmentation of metabolism not only causes an increase in the nitrog- enous excretion in general proportional to the supply of proteid, but also the carbon contained in the supply of proteid is again excreted, for of the proteid fed no portion is deposited in the body as fat or carbohydrate. From both of these statements it follows that neither fat nor carbohydrate is capable of in- creasing metabolism beyond the requirements, although proteid is. The seat of active proteid metabolism after a diet rich in proteids is, according to Pfliiger, not in the increased flow of fluid, but within the proteid- containing cells which have undergone a marked alteration (saturation) as a result of the entrance of the proteid into them. This view is confirmed by the experiments of Schondorff, who found that if the blood of a fasting animal be forced through the tissues of a generously nourished animal the urea in the blood of the latter increases, while, on the contrary, if the blood of a well-nourished animal be forced through the tissues of a fasting animal the urea in the blood of the latter diminishes. As, on providing an adequate amount of proteid, mus- cular activity takes place only at the expense of proteid, and as in the decomposi- tion of this proteid neither fat nor carbohydrate results, fat or carbohydrate cannot be the source of muscular activity (Pflugcr). Other investigators are of the opinion, however, that with adequate nitrogenous nourishment energy as well as heat can be generated from fat and carbohydrate. Nourishment with Carbohydrates and Meat. The organism is capable of gen- erating fat from carbohydrates. A deposition of fat in the body thus brought about takes place only if in addition to the proteid of the meat a nutritive excess of carbohydrates is present. Such an excess of starch may be present even when the supply of starch itself is small, while the excess may even be wanting when the supply of starch is large. The result depends upon the character of the food that is supplied in addition to the starch. The larger the amount of proteid, in 444 ORIGIN OF THE FAT IN THE BODY, addition to the starch, contained in the food, the more readily is an excess of starch to be attained without the necessity of supplying too much starch. If this condition of such an excess is not fulfilled, fat does not result even with generous administration of carbohydrates. The newly formed fat possesses the same potential energy as the nutritive excess resulting from the carbohydrates administered. Deposition of fat in the body does not take place, however large the excess of proteid food, if carbohydrates or fat be not supplied at the same time. On feeding with meat and starch, or in general with a mixed diet, the amount of newly formed fat depends in no wise upon the amount of proteid decomposed, but only upon the amount of nutritive excess due to carbohydrates. Deposition of fat from carbohydrates takes place even when no proteid at all is supplied and the metabolism, therefore, must be maintained in part at the expense of a portion of the body-proteid. While for the maintenance of the metabolic equilibrium on a pure meat-diet an enormous consumption (from 2 V to ^ of the body-weight in the dog) is required, a third of the amount of meat suffices with an adequate addition of fat or carbo- hydrate. For 100 parts of fat, added to the meat, 245 parts of dry meat or 227 of syntonin can be conserved. If carbohydrates are selected instead of additional fat, 100 parts of fat correspond to from 230 to 250 parts of carbohydrate. It should, however, be borne in mind that, at least for a short time, the carbohy- drates are superior to fat as a proteid-sparer, as the fat is less completely utilized in the process of metabolism than the carbohydrates. It appears that, instead of fat, a corresponding amount of fatty acids has the same effect in the process of metabolism. Glycerin is not capable of lessening the destruction of bodily proteid, although recently I. Munk has stated that moderate amounts of glycerin introduced into the circulation are consumed in the body and through their oxidation protect a portion of the bodily fat against oxidation. According to Lebedeff, v. Voit and Arnschink, glycerin, however, diminishes the decomposition of bodily fat and is therefore a food-material. ORIGIN OF THE FAT IN THE BODY. A portion of the bodily fat is derived directly from the food, being simply deposited in the tissues after absorption. In favor of this view is the observation that with a scanty proteid diet a generous addition of meat causes the deposition of large amounts of fat in the body. The administration of fatty acids alone may also contribute to the formation of fat, inasmuch as glycerin, formed by the body, must combine with them in the process of metabolism. As a result of fattening experiments with different warm-blooded animals (pig, goose, dog), in which, in addition to a large excess of starch, only a small amount of fat and proteid is supplied, the conclusion has been reached that a direct transformation of the absorbed carbohydrates, rich in oxygen, into fatty tissue, poor in oxygen, takes place. Pfluger found that the sugar-molecule of the food, given in excess of the requirements for the development of fat in the animal, is in part oxidized and in part reduced, so that, on the one hand, carbon dioxid, and, on the other hand, the group of atoms concerned in the formation of fat, result, inasmuch as the molecular groups CH OH are reduced to CH 3 . The carbon dioxid that is exhaled when fat-formation takes place in consequence of the administration of starch is thus derived from two sources, namely, in part from the process of decomposition described, and in part from the total combustion of starch. The excessive elimination of carbon dioxid in this process of fat- formation in consequence of an excessive starchy diet must naturally cause an increase in the respiratory quotient, even above 1.2. If the carbohydrates be considered as decomposing into fat, carbon dioxid and water, 100 grams of starch or in.i grams of sugar will yield at most 41.1 grams of fat, 47.5 grams of carbon dioxid and 11.4 grams of water. Also the circumstance that bees utilize the sugar of honey in the formation of wax is in favor of the production of fat from carbohydrates. According to Pasteur and E. Voigt, glycerin can be formed from carbohydrates. Does fat result from proteid metabolism ? v. Pettenkofer and v. Voit reached the conclusion, as a result of their experiments, that fat can be formed in the ani- mal body from proteids. They fed a dog with large amounts of meat, and although all of the nitrogen thereof was excreted in the urine and the feces, a portion of DEPOSITION OF FAT AND FLESH IN THE BODY. 445 the carbon of the meat could not be recovered from the excreta. They concluded, therefore, that this carbon had been transformed into fat for accumulation in the body. This statement is contradicted by Pfluger on the basis of his own investiga- tions, which lead him to the conclusion that the doctrine of the development of fat from proteids in the bodies of animals is entirely groundless. If it were assumed that fat could be formed from proteid, such formation is not possible through simple decomposition of the proteid molecule, but rather it w^ould be necessary for decomposition first to take place and then synthesis of the decom- posed parts. Earlier investigators, who accepted the formation of fat from proteids, be- lieved that the proteids administered broke up into a non-nitrogenous and a nitrogenous atom-complex. The former, in case it did not leave the body com- pletely decomposed into carbon dioxid and water when a rich proteid diet was taken, was believed to furnish the material for the formation of fat, while the latter was supposed to leave the body oxidized principally into urea. The following experiments support the view that fat can develop from proteid furnished as food: (i) Ssubotin and Kemmerich fed nursing bitches with meat almost free from fat, and found that the greater the amount of meat eaten, the greater was the amount of milk produced and thus also of fat. In these experi- ments, however, the possibility is not excluded that the bitches utilized the fat of their own bodies in the preparation of the milk. (2) Radziejewski gave a lean dog meat almost free from fat and in addition pure rape-oil, one of whose constituents, erucic acid, does not occur normally in the animal body. When the animal, after a period of feeding of considerable length, had accumulated fat, chemical examination demonstrated that the tissues contained, in addition to erucin, also fat which otherwise is normally present in the dog. In an analogous manner Lebedeff found in a dog after feeding with lean meat and linseed-oil con- siderable amounts of linoleic acid, together with normal dog's fat. In both experi- ments, however, the normal dog's fat could have been derived from the fat of the meat fed. (3) The fat found within organs in a state of pathological fatty degenera- tion had previously often been considered as derived from the proteid protoplasm of the tissues. Even though it be admitted, says Pfluger, that the fat of the de- generated organs has developed within them, and has not gained entrance from without, it would still first be necessary to believe that the cells everywhere con- tain carbohydrates or their derivatives, which it is known with certainty can be transformed into fat by synthetic processes. Also the fatty degeneration produced in the animal body by phosphorus-poisoning affords no support for the view that fat is developed from proteid, for although a small amount of fat is found in the body after such poisoning, its development from proteid has not yet been demon- strated. In the case of fatty degeneration, there is primarily an injury of proteid bodies and in place of these fat from other sources appears in the cells in a certain measure as a reparative procedure. (4) Nageli showed that lower forms of fungi, like other plants, are able to form proteid, fat and carbohydrates synthetically from various matters, in part exceedingly simple. Thus, for example, fungi generate fat synthetically in ripening cheese probably from the products of de- composed proteid. In the decomposition of entire cadavers and their transforma- tion into a mass consisting almost wholly of palmitic and stearic acids (adippcere) in the presence of fungi, it cannot be concluded that a simple transformation of albumin into these fats takes place. DEPOSITION OF FAT AND FLESH IN THE BODY (HYPER- NUTRITION). CORPULENCE AND THE MEANS FOR ITS CORRECTION. Hypernutrition results if more food is supplied than the body is capable of decomposing and again eliminating. The digestive apparatus (collectively and in common activity) is probably capable of digesting twice as much as the re- quirements demand. The absorbed excess of food that is not decomposed is accumulated and forms the superfluous tissue. Higher animals are capable, although not in the strict sense, of surviving on an almost exclusively proteid diet. Pfluger was able to keep a dog engaged in hard work alive for an indefinite time on a diet exclusively of meat and almost free from fat. All of the vital phenomena, therefore, can be carried on by means of proteid alone. Albumin may, accordingly, 446 DEPOSITION OF FAT AND FLESH IN THE BODY. wholly replace fat in the process of metabolism. The smallest amount of lean meat that thus maintains the metabolic equilibrium is designated by Pfluger as the nutritive requirement. The supply of fat or carbohydrates exclusively is never capable of maintaining life, as the animal under such circumstances is compelled to consume its own flesh. Therefore, a certain indispensable amount of proteid must absolutely be present in every diet. If an amount of proteid be added to the food that is sufficient in itself to. fulfil the requirement and if any desired amount of fat is added, almost all of the proteid will be decomposed and almost all of the fat will be deposited as such. The conditions are much the same if carbohydrate is supplied instead of fat, except that in this case the carbohydrate is transformed in the body into fat and is deposited as such. The greater the amount of non-nitrogenous food that is supplied in addition to the nutritive requirement of proteid the more favorable are the conditions for fattening, because all of the non-nitrogenous matters are transformed into bodily fat. If proteid is not supplied in sufficient amount the deficiency may be made good by fat or carbohydrate, and in such proportion that two-thirds of the nutritive requirement may be supplied by non-nitrogenous matters. Under such circum- stances the latter replace the deficiency of proteid in accordance with the amount of their potential energy as indicated by the number of calories yielded in their combustion. From these facts it follows that the greater or smaller amount of albumin supplied with such food is decomposed almost wholly in the process of metabolism, indifferently whether much or little fat or carbohydrate is sup- plied at the same time. In direct contrast to the proteid, the amount of fat or carbohydrate that is consumed in the process of metabolism is in nowise dependent upon the amount thereof contained in the food. Generally, the amount of carbo- hydrate or fat that undergoes decomposition is the smaller the larger the amount of proteid supplied. The nutritive requirement is satisfied first and foremost by proteid, but if the amount of proteid supplied is not sufficient, the fats and the carbohydrates are also utilized in so far as the requirements demand. In order to comprehend the laws of fattening by' means of proteid and starch, it should be borne in mind that for the satisfaction of the nutritive requirement, in addition to almost the entire amount of proteid supplied, so much carbohydrate is decom- posed as will wholly suffice for the nutritive requirement. The amount of carbo- hydrate left over is deposited as fat. In accordance with the foregoing statements, on supplying equal amounts of carbohydrate a proportionately larger amount will be conserved the larger the amount of proteid furnished. The amount of nutritive requirement, that is, the smallest amount of fat-free meat that alone establishes metabolic equilibrium, is governed by the flesh-weight of the animal and increases in direct proportion to this. A fat animal has, there- fore, apparently a smaller nutritive requirement only because the total amount of fat, acting as a similar amount of dead matter, consumes nothing. The decomposition in the process of metabolism of the proteid taken with the food increases with the supply, even when this far exceeds the requirement, but a portion of the excess is always conserved. In this manner there is a gradual deposition of flesh in the body. As the amount of proteid supplied with the food has practically no influence upon the deposition of fat in the body, and the carbohydrates are generally not so useful as proteid, fat will be produced most advantageously with the smallest amount of proteid possible, but with the largest possible amount of starch in the food. If an animal on a mixed diet in a moderate state of fattening be given a further supply of proteid, this will at once satisfy a portion of the nutritive requirement, which theretofore had been satisfied by non-nitrogenous matters. These therefore can be dispensed with and are deposited as fat. With a diet of meat exclusively deposition of flesh is possible only when the proteid of the food exceeds the requirement. The largest portion of the excess of proteid is decomposed and some is deposited. With increase in the weight of flesh, the consumption of proteid soon increases, and, accordingly, the amount of excess diminishes. It is, therefore, one of the properties of proteid food that it tends speedily to neutralize the conditions necessary for the deposition of flesh if these are present. With a mixed diet deposition of flesh can be attained only if the supply of proteid exceeds the amount indispensable. Under such circumstances only from 7 to 9 per cent, on the average, at most 16 per cent., of the proteid supplied, is conserved by the non-nitrogenous articles of food. The deposition of flesh is then the greater the larger the amount of proteid contained in the food. Of the proteid CORPULENCE AND THE MEANS FOR ITS CORRECTION. 447 consumed the body can deposit only one part of proteid, while nine parts are decomposed. In addition, for two parts of decomposing proteid one part of fat is formed from the carbohydrate supplied in excess. Excessive deposition in the body of man, corpulence, is to be considered an abnormal manifestation of metabolism, which to the subject may be a source not alone of inconvenience, but also of disorders or even of serious danger. With reference to the causes of obesity, a certain degree of congenital predisposition (in from 33 to 56 per cent, of the cases) cannot be denied, inasmuch as members of certain families increase more readily in weight (as is likewise true of certain breeds of animals) , while others, even when supplied with an abundance of food, which may reach enormous amounts, remain thin. The principal cause, however, is an habitually excessive supply of food beyond the normal metabolic average, although almost every corpulent person will with complacent self-deception main- tain that he really eats remarkably little. The mistake should be avoided of considering the corpulent individual as always excessively fat. The process of overfeeding results at first in the deposition both of fat and of flesh. On continuance of the process the development of muscular tissue diminishes, because in consequence of his clumsiness and helpless- ness the corpulent individual is rendered inactive. As a result, the nutrition of the muscular structures is secondarily impaired. Some active corpulent individ- uals, however, retain their large deposition of flesh throughout life. If, however, those factors become especially operative later on that favor the production of fat, corpulence may be transformed into obesity exclusively, as, naturally, is fre- quently the case. The following influences favor the development of corpulence: (i) An excessive diet of proteid, with a corresponding addition of fat or carbohydrate. The proteid of the food serves for the deposition of albuminates in the body, while the fat is produced by the ingestion of fat and carbohydrates. (2) Diminished consump- tion of nitrogen in the body, in consequence of (a) lessened muscular activity (little movement, much sleep), (b) Enfeeblement of the sexual functions, as shown by the fattening of castrated animals, as well as the circumstance that women readily become corpulent after cessation of menstruation, probably in consequence princi- pally of withdrawal of the stimulating influence of vascular activity, (c) Dimin- ished mental activity (obesity of idiocy), phlegmatic temperament, probably for the foregoing reason. Conversely, vigorous mental activity, an excitable tem- perament, anxiety and grief counteract the fattening process, (d) The corpu- lent individual need consume relatively less material for the generation of heat in his body, partly because his compact body, in consequence of the greater concentration of mass, gives off less heat from the external integument than a delicate slender body, and partly because of the thick layer of fat as a poor con- ductor of heat prevents direct loss of heat by conduction. As a result of the relatively lessened production of heat in the body thus required, there may be an increased deposition of tissue, (e) A reduction in the number of red blood-cor- puscles, which stimulate oxidation-processes in the body, is generally followed by an increase in the amount of fat. Corpulent persons are, therefore, not rarely fat because they are anemic. Women with a reduced number of red blood-cor- puscles are generally fatter than men. (/) The use of alcohol favors the conserva- tion of fat in the body, because, on account of the readiness with which it is oxidized, it protects the fat in the body from combustion (the obesity of drunkards) . In addition to the great inconvenience due to the weight of the body, cor- pulence, and particularly obesity, is attended with certain disadvantages and dangers. Among these are dyspnea, readiness of fatigue, the development of intertrigo in the folds of the skin and of so-called fat-hernia, and finally the danger of fatty degeneration, of cardiac paralysis and of apoplexy. For the correction of obesity the following measures should be adopted: (i) Uniform reduction of all of the articles of food to the proportions of the normal diet. The obese patient should weigh himself and his daily amount of food from week to week. So long as he observes no reduction in body- weight, the amount of food (in spite of the appetite) should be gradually and uniformly reduced. This course should be pursued slowly, without unduly sudden limitation. Almost all good resolutions fail in the face of the excellent appetite. A moderate reduction of the fat and the carbohydrates in the normal diet would at the same time result in consumption of the fat of the body itself. Such individuals as are still capable of muscular 'activity may be permitted 156 grams of proteid, 43 grams of fat, 114 grams of carbohydrates. Those in whom hypostasis, hydremia, and respira- tory difficulty have developed may be permitted 170 grams of proteid, 125 grams 448 THE METABOLISM OF THE TISSUES. of fat and 170 grams of carbohydrates. It is, however, not advisable to restrict a corpulent person excessively as to fats and carbohydrates alone, as is customary in the so-called cure of Banting. Such a violent modification of the normal diet is often attended with profound derangement of the entire metabolism. Many persons have suffered greatly in health as a result of this procedure. Every long- continued limitation of diet in one direction is deleterious and will accordingly result in emaciation, but not without danger, for it has a disturbing influence upon the entire metabolism and thus in a given sense is pathological. (2) It is advisable during the principal meals to avoid as much as possible the use of fluids of all kind (until about three-quarters of an hour later) , because by this means the absorption and the digestive activity in the intestine are rendered less effective. (3) Muscular activity should be increased by vigorous work, and also mental activity should be encouraged. (4) Heat-dissipation should be favored by cold baths of long duration, followed by vigorous friction of the skin to the point of bright redness. At the same time the clothing should be light. The patient should sleep in a cool room and for not too long a time. In this manner the increased ingestion of tea and coffee also is useful, actively stimulating the cuta- neous circulation and thereby the dissipation of heat. (5) Mild laxatives, such as acid fruits, cider, alkaline carbonates (Marienbad, Carlsbad, Vichy, Neuenahr, Ems, etc.), have a favorable influence in the correction of obesity by increasing the evacuations from the intestines and diminishing absorption. (6) If, in the pres- ence of marked deposition of fat, there is already danger of enfeeblement of the action of the heart an attempt should be made, with caution, by means of in- creased muscular activity (mountain-climbing and the like), to stimulate the heart and to strengthen its musculature. By this means the circulation is improved and metabolism becomes more active, so that recovery may even yet be brought about with the aid of a sensible diet. Entirely different from the process of fattening, which consists in the deposi- tion of large droplets of fat in the fat-cells of the panniculus and about the viscera, as well as in the bone-marrow (but never in the subcutaneous connective tissue of the eyelids, the penis, the red margin of the lips, the ears, the nose), is the con- dition of fatty atrophy or fatty degeneration, which occurs in the form of fatty granules in the albuminous tissues, for example, in muscle-fibers (of the heart), glandular cells (liver, kidneys), cartilage-cells, lymph-corpuscles and pus-corpus- cles, as well as in divided nerves. If this process increases in the tissues to such a degree that the albumin is as a result made to disappear without being again restored, the fatty atrophy or degeneration is marked. It is observed after severe fevers, marked (artificial) heating of the tissues, diminished absorption of oxygen into the body (as has been observed especially after phosphorus-poisoning), also in drunkards, after certain forms of intoxication (arsenic), and in connection with disorders of circulation and innervation. Finally, some organs exhibit fatty de- generation in connection with special diseases. In rare cases in the new-born the entire body may rapidly undergo fatty atrophy. THE METABOLISM OF THE TISSUES. All tissues require for their normal existence and for their functional activity the process of metabolism. The chief medium for this is the blood-current, which, acting as the principal traffic-carrier in the metab- olic process, conveys the material for the restoration of the tissues and re- moves the products of their vital activity. Those tissues that, like the cornea and cartilage, possess no vessels in their structure, must receive the nutritive plasmatic fluid from the adjacent capillaries through their cellular elements, which thus act as channels for the conveyance of the fluid. Therefore, interference with the normal circulation in the tissues, as, for example, through constriction or calcification of the walls of the vessels and the like, is attended with derangement of nutrition; com- plete occlusion, as, for example, by thrombosis, total compression, or artificially by ligature of all the afferent vessels, is followed by certain destruction of the tissues, which soon appears in the form of gangrene (necrosis). THE METABOLISM OF THE TISSUES. 449 Atrophy resulting from reduction in the normal supply of blood gradually dis- appears in the further course of time. In accordance with what has been stated a double current can be recognized in the fluids of the tissues, the afferent current, which brings the materials for the restoration of the tissues, and the efferent current, which removes the effete products of metabolic activity. The former will convey the albuminates, fats, carbohydrates, as well as the salts in solution, as they are taken up by the organs of absorption, for the formation of the tissues. It is clear that obstruction of any sort in the arterial system of the tissue in question will diminish this supply. The metabolism is as a result restricted, in consequence of deficient formative activity. This current can be recognized from the circumstance that after injection of a relatively indifferent, readily demonstrable substance, for instance potassium ferrocyanid, into the blood, that substance will be found in the blood within the tissues, whither it has been conveyed with the afferent current. The efferent current removes the products of metabolism, particu- larly urea, carbon dioxid, water and salts, in order to convey these with the utmost rapidity to the excretory organs. This current can be recognized from the circumstance that if a soluble sub- stance be introduced into the tissues themselves, as with a syringe for subcutaneous injection, for example potassium ferrocyanid, this will be found in the urine in the course of a few (from two to five) minutes. If the efferent current from the tissues is so strong and so large that the excretory organs are unable to eliminate the waste matters from it, these may again wander through the tissues. Such a condition is ob- served after subcutaneous injection of considerable doses of poisonous substances, which often enter the blood in such large amount that, before they can be eliminated, they are conveyed to other tissues, for example the nervous system, upon which they exert their effects before any considerable degree of elimination has taken place. If large amounts of foreign substances are injected they may even be temporarily de- posited partly in other tissues, particularly in the liver and the bone- marrow. As the afferent current traverses two canal-systems, the veins and the lymphatics, it is clear that obstruction of these paths will disturb the metabolism as a result of interference with the normal removal of effete matters. On tight constriction of a peripheral portion of the body, in consequence of which veins and lymphatics are compressed, stagnation of the current takes place to so marked a degree that even swelling of the tissues may result. In the propagation of the currents in the tissues the activity of the muscles is of great importance, inasmuch as not only do they favor the movement of the fluid in the vessels by pressure within the yielding tissues, but also where they are attached to the periosteum, the peri- chondrium and the joints they cause changes in the form of the inter- stices and thereby influence the movement of the fluid within the latter by alternate contraction and relaxation. H. Nasse found the specific gravity of the blood in the jugular vein 0.225 in a thousand higher than that of the blood in the carotid artery, and contain- ing 0.9 part more by weight in 1000 of solids. One thousand cu. cm. of blood yield in circulating through the head more than 5 cu. cm. of transudate to the tissues. 29 450 THE METABOLISM OF THE TISSUES. The activity of metabolism in the tissues and at the same time the in- tensity in the varying currents depends upon diverse factors : 1. Upon the activity of the tissues themselves. The increased activity of an organ can be recognized from the larger amount of blood contained in it and the increased activity of the circulation, which in turn are the media for the metab- olism. If an organ is subjected to complete inactivity, for example a paralyzed muscle or the peripheral extremity of a divided nerve, the amount of blood an'd its interchange soon diminish. The organism sends its fluids only to active tissues. The affected part becomes pale and flaccid and finally undergoes fatty degenera- tion. For some organs increased metabolism in association with their activity has been demonstrated, for example the muscles. Langley and Sewall have been able to observe microscopically the metabolism in thin lobules of glands during life. The cells both of the serous and of the mucous and peptic glands become filled in the state of rest with coarse granules, dark in transmitted and white in reflected light, which are consumed during the period of activity. During sleep, in which most of the organs are at rest, metabolism is restricted. It is likewise diminished by darkness, while it is stimulated by light (obviously through nervous influences). The variations in total metabolism will be reflected in the elimination of carbon dioxid and urea, which in conformity with the activity of the organism yields a curve that is fairly parallel with that for the daily variations in respiration, pulse and temperature. 2. Also the state of the blood has a distinct influence upon the currents in the tissues on which the metabolism depends. A highly concentrated blood deficient in water (such as is observed after profuse sweating, copious diarrhea, for example in cases of cholera) renders the tissues dry; while, conversely, the taking up into the blood of large amounts of water renders the tissue more succulent, even to the point of dropsy. The presence of a considerable amount of sodium chlorid in the blood and a reduction in the amount of oxygen in the red blood-corpuscles, the latter in association with muscular exertion causing dyspnea, give rise to increased disintegration of albuminates and thus to increased production of urea. Therefore, exposure to rarefied air causes increased elimination of urea. Certain abnormal changes in the blood are noteworthy: Thus, carbon-monoxid blood is not capable of abstracting oxygen from the air and conveying carbon dioxid from the tissues. The presence of hydrocyanic acid in the blood immediately interrupts the chemical oxidation-processes carried on through the blood; the tissues no longer remove oxygen from the bright-red blood overladen with oxygen, and there thus results asphyxia from interference with the internal respiration. Fer- mentative processes also are interfered with in the same way by hydrocyanic acid. A reduction in the total volume of blood causes, on the one hand, the passage of a larger amount of water from the tissues into the vessels, while, on the other hand, it retards the absorption of substances from the tissues (for example, poisons or pathological exudates) or from the surface of the intestine. If the substances derived from the tissues are rapidly eliminated from the blood, or transformed therein, subsequent absorption takes place the more rapidly. 3. The blood-pressure has an influence upon the fluid-current, inasmuch as marked increase of pressure renders the tissues richer in fluid, but the blood itself more concentrated (up to from 3 to 5 in 1000). That pressure upon the afferent vessels causes the escape of blood-plasma through the walls of the capillaries can be demonstrated on a surface of corium denuded of its epidermis, as, for example, in a blister. Reduction of the blood-pressure will have the opposite effect. After administration of phosphorus, copper, ether, chloroform, and chloral, the oxidation- activity in the animal body is diminished. 4. Elevation of the temperature of the tissues (for several hours during the day) does not cause increased destruction of proteid and fat. This subject is discussed also on pp. 404, 406 and 409. 5. An influence of the nervous system upon the tissue-metabolism has also been observed. Doubtless this influence is a double one. In the first place it may be exerted indirectly through the intermediation of the vessels, the vascular nerves causing contraction or dilatation of the vessels, and thus increasing or diminishing the amount of blood passing through the vessels. In this connection attention should be called especially to pathological conditions, abnormal stimulation or paralysis of the vascular nerves or their centers. Independently of the vessels, however, certain special nerves that have been designated trophic control the metabolism in the tissues. Atrophy caused by nerve-paralysis increases the longer it persists. Examples of metabolism in tissues excited directly through the nerves are the secretion of saliva on nerve-irritation after exclusion of the circulation REGENERATION. 451 and metabolism on contraction of bloodless muscles. Increased respiration and apnea are not followed by increased oxidation. REGENERATION. The power of regenerating parts that have been lost varies widely in different organs and tissues. It is much more marked in the low r er animals than in warm- blooded animals. Division of the fresh-water polyp (hydra) is followed by the development of two new individuals. An entire being may even develop from every excised portion of the trunk of the body; only exceedingly small pieces give rise to incomplete reproduction. No animal regenerates portions of the arm. Also the planaria exhibit similar powers of regeneration. From every portion of the umbrella of certain medusae (thaumantiades) , if it contain only a portion of the margin, a new medusa may develop. From the surface of a piece of the trunk of a turbellaria directed downward a pedal extremity develops, from the upper surface a cephalic extremity, and if attached horizontally heads develop at both extremities. Artificial division is possible also in rhizopods and infusoria. Divided infusoria regenerate only if the divided portion contains a part of the nucleus. Transversely divided earthworms (lumbriculus variegatus) regenerate entirely to whole individuals. The decapitated head has been observed to re- generate five times. In starworms the excised snout, together with the pharyngeal ring of the central nervous system, regenerates. Spiders and crabs regenerate feelers, legs and claws; snails, parts of the head, including feelers and eyes, providing the central nervous system is uninjured. Some fish are capable of replacing repeatedly destroyed fins, principally the caudal fin. Salamanders and lizards exhibit regeneration of the entirely lost tail, with bones, muscles and even the posterior extremity of the spinal cord. In young frogs amputated legs regenerate, but only when the bones also are divided, and not after ex- articulation. In tritons the lower jaw regenerates. In order, however, that this regeneration shall take place a stump at least must be left. Total extirpation of the parts mentioned destroys the power of regeneration. Loeb designates as heteromorphosis the phenomenon that occasionally after injuries supernumerary parts appear that otherwise do not belong in such situa- tions. Thus, for example, in young lizards lateral notching of the tail may cause the growth of a second tail from the wound; likewise supernumerary extremities develop in tailed amphibia after amputation. Planaria injured on the head exhibit the growth of a second head. In amphibia and reptiles the regeneration of organs and tissues follows, on the whole, the type of embryonal development, and the histological processes in the growing caudal extremity and in regenerating portions of the body of earth- worms take place in the same manner. In amphibia and reptiles only tissue of the same kind develops from injured tissue. The spinal cord regenerates from the epithelial cells of the central canal. In the process of tissue-formation the leukocytes assume only the function of nutrition and conveyance of material. It is a remarkable fact that tadpoles develop after destruction of the brain and the medulla and functional exclusion of the spinal cord. The power of regeneration is much more restricted in warm-blooded animals and in man. In these also it is confined principally to early life. True regenera- tion is exhibited by 1. The blood; first the plasma, then the white and finally also the red blood- corpuscles. 2. The epidermal structures and the epithelium of the mucous membrane re- generate by cell-division in the deepest layers after previous nuclear division. After direct loss they regenerate so long as the normal matrix upon which they grow and the deepest layer of cell-protoplasm capable of development is not also destroyed. In the latter event, regeneration ceases and restoration must take place from the margins of the deficiency. In the process of regeneration, there- fore, growth takes place always either from the deep layers, or, after their de- struction, from the margins. There develop under such circumstances proto- plasmic wandering cells that in part become detached and help to close the deficiency, and in part the deepest layer of cells develops into large, multinu- cleated protoplasmic cells, which multiply by division into polygonal flat nu- cleated cells. The nail grows from the posterior fold forward, on the fingers in the course of from four to five months, on the great toe in about twelve months (and more 452 REGENERATION. slowly in extremities with fractured bones). Its matrix extends as far as the lunula, and its total or partial destruction causes corresponding loss of the nail. The eyebrows are changed in from one hundred to one hundred and fifty days, the remaining hairs more slowly. Destruction of the papilla in a hair-follicle prevents regeneration. Cutting accelerates the growth of the hair, although cut hair does not grow longer than uncut hair. After attaining a certain length the hair falls out. The hair never grows at its free extremity. The epithelial cells of the mucous membranes and the glands appear to be subjected to a regular cycle in their utilization and in the regeneration of new cells. In the mammary gland and likewise in the sebaceous glands partial desquamation of secretory cells, and also their regeneration, are evident. The regeneration of spermatozoa takes place through spermatoblasts. In catarrhal conditions increased desquamation and regeneration of epithelial cells take place upon the mucous membranes, together with the appearance of indifferent cell-forms (leukocytes) in large number. The crystalline lens, which represents an invaginated epidermal sac that has become independent, regenerates like epithelial structures. Its matrix is the anterior wall of the capsule, with the single layer of cells present in this situation. If the lens is removed, but with preservation of these cells, regeneration takes place, the cellular elements becoming elongated into lenticular fibers and filling the entire cavity of the empty capsule. The removal of large amounts of water from the body may cause turbidity of the lens. 3. The blood-vessels exhibit extensive regeneration, which takes place in the same way as the formation of the vessels, but this has already been discussed. There always develop at first capillaries, about which, later on, the characteristic tissue-elements are deposited from without in places that subsequently are to become arteries or veins. In case of injury or permanent occlusion of a vessel, at least the portion to the next collateral vessel is always wholly obliterated, derivatives of the endothelial cells, connective-tissue corpuscles from the vessel- wall and wandering cells being transformed into the spindle-cells of the obliterating cicatrix. On the blood-vessels of young and adult animals blind and solid pro- cesses are present as an evidence of constant obliteration and regeneration of the vessels. The lymphatics behave in the same way as the blood-vessels. After removal of lymphatic glands regeneration may take place, especially when stasis of lymph is present. 4. The contractile substance of the muscular -fibers may undergo regeneration if destroyed by injury or degenerative processes. The contractile, transversely striated contents of the sarcolemma undergo granular or fibrillar degeneration, or break up into discs or plates, the latter being observed in connection with waxy degeneration of the abdominal muscles in cases of typhoid fever. At the same time nuclei in large number appear within the sarcolemma, as well as in this itself, and the previously contractile contents are converted into cell-proto- plasm. In the course of a few days mitotic cell-division is observed. The proto- plasm exhibits at first fine fibrillary longitudinal striation. From this fibrous tissue of myogenous origin, transversely striated, nucleated fibers may be devel- oped in the course of months. In case of considerable loss of muscular tissue or gaping wounds a fibrous cicatrix forms. In fibers injured through subcutaneous wounds Neumann observed, after from five to seven days, a budhke prolongation of the divided extremities, at first without transverse striation, which, however, appeared, later. Unstriated muscle-fiber may regenerate after injury. The nuclei of the injured fibers divide by karyokinesis and about each newly formed nucleus a new muscle-fiber develops in consequence of the differentiation of the surrounding protoplasm. The fibers divide in the middle of their length. 5. Immediate reunion of a divided nerve never takes place with immediate restoration of function. If a portion of a nerve- trunk be excised, the peripheral extremity of the nerve degenerates first, the medullary sheath and the axis- cylinder being transformed into cells. The deficiency is soon filled with juicy connective tissue. The process pursued later in the regeneration of nerve-fibers is fully considered on p. 636. It is an especially noteworthy fact that in the peripheral nerves a constant loss by fatty degeneration, associated with consecutive regeneration of fibers, takes place. Regeneration of peripheral ganglion-cells does not occur. On the other hand, v. Voit observed in a decerebrated pigeon, after the lapse of five months, a regenerated nerve-mass in the skull, consisting of medullated fibers and central ganglia. Also, Vitzou has reported the regeneration of destroyed cerebral ganglion-cells after the appearance of karyokinesis in the adjacent cells. Eichhorst and Naunyn found in young dogs in which the spinal cord was divided between the thoracic and the lumbar portion that an anatomical REGENERATION. 453 and functional regeneration takes place, so that voluntary movements again occur. Vaulair observed in frogs and Masius in dogs first motility, then sensi- bility, return. Regeneration of the spinal ganglia did not take place. According to Stroebe a formation of fibers takes place in a small, limited area at the site of injury to the spinal cord of the rabbit, but not complete regeneration of the actual spinal tissue. 6. In some glands the regeneration of their cells during normal activity is exceedingly active, for example the sebaceous glands, the mucous follicles of the stomach, the glands of Lieberkuhn, the uterine glands, the mammary glands during pregnancy; in others regeneration is less active. The removal of consider- able portions of various glands is not followed, as a rule, by regeneration, while after injury of glands regeneration of the affected parts does not take place if suppuration occurs. Regeneration of the biliary passages, the bile-duct, and of the pancreatic duct, is remarkable. After injury of the liver Tizzoni and Colluci, as well as Griffini, observed the regeneration of liver-cells and biliary passages even beyond the normal limits of the liver. Pisenti reports similar observations upon the kidney. After injury to the liver Podwisotzky observed the deficiency disappear com- pletely through partial multiplication of the liver-cells and partial hyperplasia of the epithelial cells of the biliary passages, which are likewise transformed into true liver- tissue (resembling the embryonal development of the liver) . Ponfick extir- pated even three-quarters of the liver, and regeneration set in within a few days after the operation and was complete in the course of a few weeks. According to Philippeaux and Griffini regeneration may take place after partial removal of the spleen, according to Laudenbach, in the dog, even after almost complete removal. After mechanical injury to the secretory cells of certain glands (liver, kidney, salivary, mammary, Meibomian) hyperplasia and division of adja- cent cells take place for the purpose of regeneration. The nipple of which half has been extirpated undergoes regeneration. 7. Of the connective tissues, cartilage, providing its perichondrium remains intact, appears to regenerate by division of the cartilage-cells, although, probably, loss of tissue is most frequently replaced by connective tissue. 8. After incised wounds of tendons reunion takes place through the agency of the tendon-cells themselves. These multiply considerably by utilizing the matrix for the formation of cells and by mitotic division of the latter. If the extrem- ities of the divided tendon are widely separated, granulation-tissue forms for the development of a cicatrix, as a result of marked reaction in the surrounding connective-tissue tendon-sheath. 9. The regeneration of bone is remarkable. If the articular extremity, together with the adjacent portion of the bone, be resected, it may be regenerated, although an appreciable shortening results. Pieces of bone that have been broken or sawed off reunite if replaced; likewise teeth that have been removed and replaced in the alveolus. An isolated piece of periosteum, even if transplanted to another bone, gives rise to a piece of bone of corresponding size. Defects in bone are readily filled by bony tissue if the periosteum be preserved. For this reason the surgeon in resecting diseased bones carefully preserves the periosteum, in the hope that the bone will regenerate from it. The medulla of bone may also regenerate. The internal medullary membrane is capable, if transplanted, of producing bony tissue in small amount from the osteoblasts present. If a bone, for example a long bone, has been fractured, a circular thickened deposit, at first of rather gelatinous, vascular and cellular, later of firmer car- tilaginous, character, forms from the periosteum upon the external surface at the site of fracture the external callus. A similar process takes place at the same time within the medullary cavity, which is thereby diminished in size internal callus. These formations are due to cell-multiplication, in part from the perios- teum, in part from the medulla and the bone-tissue itself. The callus generally resembles tissue, and is often cartilaginous. In the external and internal callus calcification of the cartilage later takes place, as well as the deposition of osseous lamellae, which, acting as rings, fix the fractured extremities. Later (up to the fortieth day) a thin layer of the same material forms between the fractured extremities, and this subsequently under- goes ossification intermediate callus. With the final solidification of the latter, the bony matter of the external and internal callus gradually disappears. Ex- ternally, the swelling disappears, internally the medullary canal becomes again of uniform size and the intermediate callus eventually acquires the same archi- tecture as the adjacent portions. Bone-fractures toward which the course of the 454 TRANSPLANTATION AND ADHESION. nutritive vessels of the bone is directed are said to heal relatively more readily and more rapidly. With reference to the growth and the metabolism of bones a number of in- teresting observations may be recorded: (i) Exceedingly small amounts of phos- phorus or arsenous acid, added to the food, cause marked thickening of the bones. This appears to be due to the fact that the portions of bone that undergo absorp- tion in the process of normal growth for example, the walls of the medullary cavity are not absorbed, but persist, while new growth continues to take place. Small doses of phosphorus are employed for the correction of rachitic softening of bone. In cases of osteomalacia Neumann found an increased elimination of phosphoric acid with the urine. (2) Complete exclusion of lime from the food does not impair the growth of the bones, but makes them thinner, all parts, even the organic matrix of the bone, undergoing uniform atrophy. (3) The ingestion of madder (rubia tinctorum) makes the bones red, the pigment being deposited in the osseous tissue together with the calcium-salts. In birds the egg-shell like- wise is stained. (4) Long-continued administration of lactic acid has a solvent influence upon the osseous tissue. The ashy constituents of the bones are dimin- ished. The changes in the bones in youth induced by the withdrawal of calcium- salts are increased by administration of lactic acid. The bones resemble rachitic bones. Osteomalacia in women can be relieved by castration. (5) Artificial hypostatic hyperemia is capable of increasing the growth of bone. The normal growth of bone is considered in connection with its embryological development. At all portions of the body where considerable amounts of tissue have been lost, with secondary inflammation, such defects heal by the formation of a cicatrix of the structure of connective tissue that fills the defect. After injury to permanent connective tissue there occurs in the course of three hours an abundant multiplication of the nuclei, which are derived from the matrix, followed by the formation of cells (awakened slumbering cells) , while the fixed connective-tissue corpuscles undergo increase in size. After the formation of the previously slumbering cells from elastic and gelatinous fibers has continued for one or two days, mitotic division is observed particularly early in the cells of the adjacent capillaries, then also in the tissue-cells themselves. This often per- sists for more than eight days. The spindle-cells form blood-vessels, which bridge over the wound-defect, and soon also bundles of fibers, that is, a young cicatrix. The larger the number of cells that become fibers, the firmer becomes the cicatrix; the vessels atrophy and the old cicatrix is firm and deficient in vessels. The formative process described occurs in all situations where lost tissue is replaced by connective tissue. On the free surface of the body the newly formed vascular tissue not rarely grows (from wounds and ulcers) above the adjacent level proud flesh. This soon returns, however, to the normal level (after the application of astringents to the vessels), becoming pale, and, finally, after a protecting layer of epidermal cells has developed upon the free surface, forms the cicatrix. If the continuity of a tissue has been severed by a wound, as, for example, an incision, the divided surfaces may, after careful apposition, unite directly, without inflammation union by primary intention. The surfaces are at first held together by blood-plasma, and later on direct union of the parts takes place. Divided blood-vessels, however, never reunite to form a blood-channel. The cut surfaces of nerves often unite directly, but direct physiological restoration does not take place. Wherever direct union does not take place, cicatricial connective tissue forms in the sequence of inflammation and suppuration union by secondary intention. TRANSPLANTATION AND ADHESION. Parts of the body, such as the nose, the ears, and even the fingers, if severed by means of a sharp and clean-cutting surface, may unite, even after the lapse of hours, an evidence that the life of severed tissues may persist for a time. As a matter of fact, some tissues detached from the body may continue to live for a considerable time, for example leukocytes for three weeks, ciliated epithelium for eighteen days. The transplantation of flaps of skin is often practised by surgeons to effect closure of existing defects. The flap of skin intended for transplantation, and detached from the subjacent tissues, is permitted to remain for a time attached by means of a pedicle in its original position, and its margins are united accurately INCREASE IN SIZE AND WEIGHT IN THE PROCESS OF GROWTH. 455 by suture to the freshened margins of the deficiency, the pedicle being divided only after the approximated margins have united firmly. In this way, a new cutaneous covering for the nose can be formed from the skin of the back from another person, or from the skin of the patient's own arm, or from the skin of the forehead. It is possible also to transplant even large, entirely detached flaps of skin, without a pedicle, even after they have been preserved for fifty hours in 0.6 per cent, sodium-chlorid solution at room-temperature. To form a cutaneous covering for large granulating (previously carefully cleansed) ulcerous surfaces Reverdin and Thiersch apply under pressure numer- ous rapidly detached bits of cutis the size of beans upon the granulations, or after removal of the latter upon the freshened wound-surface, where they become adherent. From the margins of these fragments newly formed layers of epidermis extend over the entire surface of the ulcer. Enderlin was able to employ successfully such fragments after preservation for four days moistened with physiological salt-solution. The excised spur of the cock can be made to grow upon the comb. Bert transplanted the denuded tails and feet of rats beneath the skin of the back of other rats. The transplanted parts became adherent and formed vascular communications with adjacent tissues, and even their bony parts increased in size. Parts excised as long as three days previously exhibited similar phenomena. Detached portions of periosteum transplanted to other situations likewise heal in place and even develop bone. Extracted teeth may be replaced and even in a second person, v. Hippel transplanted successfully a piece of a rabbit's cornea 4 mm. square in a defect in a human eye, the clear membrane of Descemet being preserved as a foundation, but the transplanted structure sub- sequently became turbid. Also blood and lymph can be transfused. All of the transplantations mentioned succeed almost solely between individuals of the same species. Most tissues, however, are not susceptible of transplantation, for example muscles, nerves, glands and organs of special sense. In the lower animals, even entire parts can be transplanted; for example two pieces of different earthworms may unite, and also of hydra. The union of two higher animals (rats and others) was successfully effected first by Bert in 1862, who divided the skin of the trunk and united the margins of the wounds in the respective animals by suture. Union had taken place in the course of five days. When atropin was administered to one of the animals the pupils of both dilated. Post-mortem injection demonstrated the exist- ence of anastomoses between the vessels of both. That such union may take place also in man is shown by the experiments related on p. 454. The procedure might be of therapeutic significance, as the possibility does not appear excluded that the union of the skin, for example along the extensor aspect of the two fore- arms, might result in an influence of the one individual upon the other, whether to the end of conveying nutritive juices, or for the removal of certain substances from the body of the one (as for example in case of insufficiency on the part of certain excretory organs), or for the transmission of antitoxins and the like. INCREASE IN SIZE AND IN WEIGHT IN THE PROCESS OF GROWTH. In the first period after birth the length of the body, which on the average is - 1 of that of an adult, exhibits the most rapid increase; in the first year about 20 cm., in the second 10 cm. more, in the third about 7 cm.; from the fifth to the sixteenth year the annual increase (about 5^ cm.) is pretty much the same. From the twentieth year on, only slight growth takes place. From the fiftieth year on, the size of the body diminishes, principally in consequence of attenuation of the intervertebral discs. The reduction may reach 6 or 7 cm. up to the eightieth year. The weight of the body (about ^ of tnat of the adult) diminishes constantly in the first five days or week after birth in consequence of evacuation of meconium and of the small amount of food taken at first, together with increased functional activity (generation of heat, respiration, digestive activity), as a result of which the metabolic products are considerably augmented. Not before the tenth day does the weight of the child again equal that of the newborn. Later on, the increase in weight exceeds that of the increase in length of the body during corre- sponding periods. In the first year the weight is trebled. In man, the maximum is reached at about the fortieth vear. At about the sixtieth year reduction in 456 SUMMARY OF THE CHEMICAL CONSTITUENTS OF THE ORGANISM. weight sets in, in consequence of the retrogressive nutritive processes of age, and this may reach about 6 kilos up to the eightieth year. The detailed figures are given in the following table : Age. Length Male. (cm.) female. Weight Male. (kilos) Female. Age. Length Male. (cm.) Female. Weight Male. (kilos) Female. 49.6 48.3 3-20 2. 9 I 15 155-9 I 47-5 46.41 41.30 I 69.6 69.0 IO.OO 9.30 16 161.0 150.0 53-39 44-44 2 79.6 78.0 12. OO 11.40 *7 167.0 154-4 57-40 49.08 3 86.0 85.0 13.21 12.45 18 170.0 156.2 61.26 53-10 4 93- 2 91.0 I 5-7 14.18 *9 170.6 63-32 5 99.0 97.0 16.70 I 5-5 20 171.1 I 57- 65.00 54.46 6 104.6 103.2 18.04 16.74 2 5 172.2 157-7 68.29 55-o8 7 III. 2 109.6 20. 16 18.45 3 172.2 *57-9 68.90 55- I 4 8 II7.0 II3-9 22.26 19.82 40 !7 J -3 I S6-5 68.81 56-65 9 122.7 120.0 24.09 22.44 50 167.4 153-6 67-45 58.45 10 128.2 124.8 26.12 24.24 60 163.9 151.6 65-50 56.73 ii I 3 2 -7 I2 7-5 27-85 26.25 70 162.3 i5 r -4 63-03 53-72 12 J 35-9 132.7 31.00 30-54 80 161.3 150.6 61.22 51-52 13 140.3 138.6 35.32 34.65 9 57.83 49-34 14 148.7 144.7 48.50 38.10 In the first three days the newborn child loses from 170 to 222 grams in weight. Nourished with mother's milk, the child doubles its weight in the first five months and trebles it in the first year. The weight of a five-year-old child is double that of a child one year old, and that of a twelve-year-old child double that of a child five years old. Between the twelfth and the fifteenth year, the weight and the size of girls are greater than those of boys, on account of the earlier advent of puberty in girls. Growth is most rapid in the last months of fetal life; then from between the sixth and the ninth year to between the thirteenth and the sixteenth year. At about the thirtieth year the length of the body is complete, while the weight is not. Normally developed individuals weigh as many kilos as their length measures in centimeters after subtraction of the first meter. As compared with the growth of the entire body, the individual parts exhibit wide variations. The brain grows least, namely, only to the third year, and from this time on scarcely at all. Also the liver and the intestines grow little, while the heart, the spleen and the kidneys grow only in slightly lesser measure than the entire body. Fat, and particularly muscles, grow more than the entire body. SUMMARY OF THE CHEMICAL CONSTITUENTS THE ORGANISM. INORGANIC CONSTITUENTS. OF Water constitutes 58.5 per cent, of the entire body and is present in the different tissues in widely varying amounts. The tissues of the kidneys contain the largest amount of water, namely 82.7 per cent., while the bones contain 22 Eer cent., the teeth 10 per cent, and the enamel at least 0.2 per cent. Schonbein Dund some hydrogen dioxid in the urine. Gases: Oxygen, ozone, hydrogen, nitrogen, carbon dioxid, methane, am- monia, hydrogen sulphid. Salts: Sodium chlorid, potassium chlorid, calcium chlorid, ammonium chlorid, calcium fluorid, sodium carbonate, sodium bicarbonate, calcium carbonate, sodium phosphate, alkaline disodium phosphate, acid monosodium phosphate, neutral potassium phosphate, acid potassium phosphate, tribasic calcium phos- phate, acid calcium phosphate, magnesium phosphate, neutral sodium sulphate, potassium sulphate, calcium sulphate. Free acids: Hydrochloric acid (and sulphuric acid in the saliva of some snails, for example dolium galea). Silicon (as silicic acid), manganese, iron in the blood (and combined with a proteid as ferratin, which aids in blood-formation), iodin (in the thyroiodin of the thyroid gland, diminished in the presence of goiter, increased after administra- tion of iodid) , copper ( ?) . THE TRUE ALBUMINOUS BODIES. 457 On the whole, a man weighing 70 kilograms consists of thirteen elementary substances, namely, 44 kilograms of oxygen, 7 kilograms of hydrogen, 1.72 kilo- grams of nitrogen, 0.8 kilogram of chlorin, o.i kilogram of fluorin, 22 kilograms of carbon, 800 grams of phosphorus, 100 grams of sulphur, 1750 grams of calcium, 80 grams of potassium, 70 grams of sodium, 50 grams of magnesium, 45 grams of iron. ORGANIC CONSTITUENTS. THE PROTEID BODIES OR PROTEIN-SUBSTANCES. THE TRUE ALBUMINOUS BODIES. The albuminous or proteid bodies, consisting of C, H, N, O and S, are the fundamental and principal constituents of the animal body, to which they are supplied through vegetable food. They are present in almost all animal and vegetable fluids and tissues, partly in liquid form, partly in more consistent, semi- solid form as constituents of the tissues. Their chemical constitution is unknown; their percentage-composition is described on p. 26. The nitrogen is combined in them in two different ways, in part loosely, in which form it can be separated on treatment with dilute hot potassium hydroxid, with the formation of ammonia; and in part firmly. According to Pfliiger a portion of the nitrogen of the living proteid portions of the body is combined in the form of cyanogen. Also the sulphur in the proteid molecule is combined in part firmly, in part loosely. The loosely combined sulphur can be split off by hot potassium hydroxid as potassium sulphid. With lead acetate it forms lead sulphid. The firmly combined sul- phur can be prepared only after destruction of the albumin. In serum-albumin the proportion of the loosely to the firmly combined sulphur is as 3 to 2 . The proteid molecule is exceedingly large, and is probably complex. A small portion of it belongs to the group of aromatic substances (which appear especially in connection with putrefaction) ; the larger portion of the molecule to the series of fatty bodies (in the oxidation of proteids, fatty acids especially develop). Also carbohydrates may appear as decomposition- products, not being entirely wanting in any form of albumin studied by Krukenberg. The decompositions in the process of digestion that are of physiological interest are discussed on p. 304, those occurring in the putrefactive processes on p. 333. The proteids form a large group of related substances, which perhaps represent only modifications of the same body. If it be borne in mind that the infant pre- pares from the casein of milk the majority of all the proteids of its own body this last view will be clear. The proteids are generally soluble in water or dilute salt-solutions, but with the exception of the peptones, are incapable of diffusing through membranes on account of the large size of their molecule. They are in- soluble in alcohol or ether. They are in general not crystallizable, so that they can be prepared in a pure state only with difficulty. They rotate the plane of polarized light to the left and in the flame they yield the odor of burned horn. They are transformed into a solid modification, that is coagulated, by heat and the long-continued action of alcohol, and are then insoluble in neutral sol- vents. Coagulated albumin is soluble only (i) in dilute alkalies, alkali-albuminate resulting, having lost a portion of nitrogen and sulphur; (2) in dilute mineral or strong organic acids, acid-albumin (syntonin) developing; and (3) by the process of digestion, albumoses and peptones being formed. By neutralization of alkali- albuminate and acid-albuminate, these substances are rendered insoluble. As a result of long-continued boiling with dilute mineral acids or alkalies, as well as of the action of steam under high tension, the proteids take up water and break up into amido-acids, with the formation of ammonia and hydrogen sulphid; on boiling with alkalies, splitting off also carbon dioxid, oxalic acid and acetic acid. Color-reactions: (i) Coagulated and heated with nitric acid proteids are stained yellow xanthoproteic acid. Supersaturation with ammonia makes the color orange. (2) If heated above 60 with Millon's reagent (mercuric nitrate with nitrous acid) a red color results. (3) Boiled with potassium hydroxid, then cooled and copper sulphate added, proteids become deep violet-blue. (4) Concen- trated hydrochloric acid (pure) dissolves them on boiling and produces a violet color. (5) Solid proteids are made blue by sulphuric acid containing molybdic acid. (6) The solution of thoroughly desiccated albumin in glacial acetic acid is made violet by concentrated sulphuric acid and exhibits the absorption-band of hydrobilirubin. (7) lodin may be employed as a microscopic reagent, staining 458 THE TRUE ALBUMINOUS BODIES. proteids brownish-yellow; also sulphuric acid and cane-sugar, which stain them purple- violet. Precipitation: (i) By boiling. (2) By strong alcohol. (3) By "salting." Most proteids are precipitated by the addition of neutral salts to their solutions to the point of complete saturation, especially if the reaction be acid. If the addition of salt be made gradually, some of the albumin can thus be separated in crystalline form. (4) Nitric acid precipitates albumin, as does also metaphos- phoric acid. (5) Further precipitants are the salts of the heavy metals (iron chlorid, lead acetate, copper sulphate, platinum chlorid, mercuric chlorid in solu- tion with hydrochloric acid). (6) Precipitation is caused by acetic acid and potassium ferrocyanid, also by tannic acid, picric acid or trichloracetic acid. (7) Mercuric-iodid, potassium-iodid on addition of hydrochloric acid, phosphotungstic and phosphomolybdic acids also precipitate albumin. Animal proteids. Albuminous bodies can be divided into several characteristic groups : The first group comprises albuminous substances in the strict sense, designated genuine albuminous substances or proteins, which are soluble in water or in dilute saline solutions and are levorotatory. This first group comprises the albumins and the globulins. The albumins are soluble in water and precipitable by complete saturation with ammonium sulphate, but not by means of sodium chlorid or magnesium sulphate. Serum-albumin has been prepared in crystalline form by Giirber. By diffusion almost all of its salts, and thereby its coagulability by heat, can be re- moved. It is precipitated by strong alcohol. It is readily soluble in concen- trated hydrochloric acid, acid-albumin, which is soluble in water, being precipitated on addition of water. Egg-albumin, C 80 H 122 N2 SO 24 + H 2 O, has been prepared in crystalline form by Hofmeister. It occurs in the white of birds' eggs and exhibits a specific rotation of polarized light of 37.8. After injection into the veins or beneath the skin, or even after introduction into the intestine in large amount, it appears partly unchanged in the urine. It is precipitated by agitation with ether. Its composi- tion is C^.zgHy.aeNisSj.og. Lactalbumin. Muscle-albumins, that is, the proteid bodies in the aqueous extract of muscle. The globulins are insoluble in water, the majority soluble in dilute salt- solutions. They contain less sulphur and yield a more marked xanthoproteic reaction than the albumins. In solution they are coagulated by a temperature of 75 C. and they are precipitated by abundant addition of water. Dilute acids con- vert them into acid- albumins. They are precipitated by saturation of the solu- tion with magnesium sulphate and also by semisaturation with ammonium sulphate, by very dilute acids, as well as by carbon dioxid. The globulins include : Serum- globulin, the presence of which in the urine is described on p. 496. Fibrinogen, from which fibrin results. The substances from which this is produced are described on p. 69. Stroma-fibrin is considered on p. 72. Myosinogen. Vitellin, which occurs in the yolk of birds' eggs and likewise in the crystalline lens, perhaps also in the chyle and in the amniotic fluid, is not precipitable by saturation of a neutral salt-solution with sodium chlorid. Crystalline vitellins occur as yolk-plates in the eggs of fish, frogs, tortoises. In the eggs of birds and in tissues the vitellins are amorphous. Alkali-albuminates. Potassium and sodium, also calcium hydroxid and barium hydroxid, form combinations with proteids, and the more rapidly the more concentrated the alkaline solution and the higher the temperature. These com- binations are designated alkali-albuminates. They exhibit especially marked cir- cumpplarization, are not coagulated on boiling and are precipitated from solutions by acids, which combine with the alkali. If, for example, egg-albumin be mixed with a solution of potassium hydroxid, potassium albuminate is formed as a gradually developing jelly, which is soluble in boiled water. Acid-albuminates. If proteids are dissolved in strong acids, for example hydrochloric acid, they acquire the properties of so-called acid-albumin, which ex- hibits great similarity to alkali-albuminate (also the specific rotation) . This body is insoluble in water and neutral salt-solutions, readily soluble in dilute hydrochloric acid. They are thrown out of solution by the addition of much salt (sodium chlorid or sodium sulphate). Also neutralization by alkali causes precipitation, though boiling does not. On cooling, the boiled (concentrated) fluid becomes VEGETABLE PROTEIDS. 459 gelatinous and again fluid when heated. The syntonin from muscle is an acid- albuminate. It is converted into myosin by milk of lime and ammonium chlorid. The second group comprises the complex albuminous bodies. These are pro- teins combined with bodies of complex composition and they are also designated proteids. They are precipitated by alcohol, which coagulates them after long- continued action. Heat does not cause coagulation. They are generally pre- cipitated from their solutions by slight acidulation. They are readily soluble in dilute alkalies. The second group comprises: Chromoproteids, that is combinations of protein with pigment. These in- clude : Hemoglobin, whose combinations and derivatives are described on pp. 55-63. Glycoproteids, that is combinations of protein with carbohydrates. These include : Mucin, probably present in various slightly different modifications. It is richer in oxygen, but poorer in nitrogen and carbon, than albumin, free from phosphorus, and contains up to 1.79 per cent, of sulphur and up to 13.5 per cent, of nitrogen. It is liquefied in water into a ropy mucous mass, but it is insoluble in water. On addition of alkali it is converted into a neutral ropy solution. It serves as a protecting substance against the entrance of injurious agents. It is precipitated by a small amount of acetic acid and is redissolved by a larger amount of the same acid. It is precipitated also by alcohol, the resulting precipitate being soluble in water. Acetic acid and potassium ferrocyanid cause no precipitation, although nitric acid and other mineral acids do. Mucin yields all the color-reactions of the albuminous bodies. It is present in saliva, bile, the mucous glands, the secretions from mucous membranes, in "mucous" tissue and in the tendons. In addition it is occasionally found pathologically in cysts (in the lower animals, especially in snails and in the skin of holothurians) . On boiling with water or on standing in alcohol it is transformed into coagulated albumin. Alkalies and lime-water transform it into alkali-albuminate, acids into acid-albuminate. On decomposition it yields leucin and 7 per cent, of tyrosin. The mucins react like glucosids. At high temperatures they break up under the influence of dilute mineral acids into a proteid and a carbohydrate, namely, animal gum. Peptone and propeptone are discussed on p. 298; their demonstration in the urine on p. 496. Peptone is found also in dry lupins, in oats, etc., and less in germinating seed. There may yet be mentioned proteic acid, precipitated from the meat-juice of animals (fish) by Limpricht with the aid of acids; and finally amyloid, encountered partly in the form of laminated granules on the brain and in the prostate gland, partly (pathologically) as a glistening infiltration of the liver, spleen, kidneys, coats of the vessels, and recognizable from the blue dis- coloration on addition of iodin and sulphuric acid (like cellulose), and the red discoloration on adding iodin. It can with difficulty be converted into albuminate by alkalies and acids. APPENDIX: VEGETABLE PROTEIDS. Plants contain, although in distinctly smaller amount than animals, proteids of various kinds. These occur either in liquid (swollen) form, particularly in the juices of living plants, or in solid form. They resemble the animal albuminates in composition and reaction. There are distinguished: I. The vegetable albumins. II. The vegetable globulins. Of the globulins forming crystals or spheroids that were formerly grouped together under the names conglutin and vitellin, together with legumin, the following may be mentioned: Edestin in grain, amandin in almonds, corylin in nuts, excelsin in the Para nut, avenalin in oats, conglutin in lupins. The globulins include as a decomposition-product glutin, an important constituent of wheat, whose glutinous property makes it possible to convert a mixture of flour and water into a coherent dough. Gluten can be obtained from wheat-flour, which may contain as much as 17 per cent., by washing the dough repeatedly with water. Thus prepared, it is viscid, gray, insoluble in water and alcohol, soluble in dilute acids (for example i in 1000 parts of hydrochloric acid) and in alkalies. Gluten results from a myosin-like globulin-substance, which is transformed by a ferment in the presence of water into gluten. III. The nucleins, which comprise a special group of readily decomposed complex proteids, containing phosphoric acid in firm combination. They form the chromatin-substance of the cell-nucleus (whence the name) , as well as the tingible 460 THE ALBUMINOID BODIES. constituents of the cell-body, and accordingly they are widely distributed in the animal and vegetable kingdoms. The nucleins have a strongly acid character. They are divided into the following two groups : 1. Paranucleins, which consist of albumin plus phosphoric acid. If more albumin is added to paranuclein, nucleoalbumin is formed. Casein is such a body, in which, besides, calcium, is present for the neutralization of the acid. It occurs in solution in the milk of all mammals, from which it can be precipitated by addition of acid or of rennet, but not by heat. In the process of gastric diges- tion nuclein is gradually separated from casein. On boiling casein with hydro- chloric acid and stannous chlorid lysatin, C 6 B. 13 N 3 O 2 , results, which yields urea when boiled with baryta-water. 2. The true nucleins, which consist of albumin plus nucleinic acid. Nucleinic acids are decomposed by hydration into phosphoric acid and xanthin-bases (nuclein-bases) . The latter include xanthin, guanin, adenin, hypoxanthin, cyto- sin. The true nucleins may combine with more albumin and yield nucleo- proteids. A carbohydrate is derived from nucleinic acid, namely pentose. The nucleins are insoluble in water or dilute acids, readily soluble in dilute alkalies, with which they unite by reason of their acid character to form neutral combinations. They swell in solution of sodium chlorid, and yield all the color- reactions of albumin. In alkaline solution they are readily decomposed into proteids and nucleinic acids (or phosphoric acid) . The nucleins resist the solvent action of the gastric juice, which is capable of dissolving and digesting only the proteids of the nucleoalbumins and nucleoproteids. Upon the latter property depends the possibility of isolating the nucleins. The nucleinic acids occur also uncombined with albumin in certain cellular structures of the animal kingdom (salmon-spawn). Nuclein-bases have been found free in animal and vegetable tissues. The yolk of the egg contains a nuclein-like body containing iron that is utilized in the formation of blood from the yolk (hematogen), and that also aids in hemogenesis on a diet of eggs. From a body, phosphosarcic acid, closely related to the paranculeins, can be prepared a ferruginous body, carniferrin, which contains iron in similar firm combination as in hematogen. Nucleohiston, a combination of nuclein and histon, which can be prepared from the erythrocytes of the goose, is readily decomposed into nuclein and histon. The latter prevents coagulation of the blood. Nucleoalbumin is prepared by Halliburton in the following manner: Kidneys are rubbed up with powdered sodium chlorid and some water. The expressed extract is poured into distilled water, in which the remains of tissue and the globulins fall to the bottom, while the mucoid nucleoalbumin floats on the surface. This is collected and washed repeatedly with distilled water. Injected into the veins nucleoalbumin causes coagulation. According to Pekel- haring, the zymogen of the fibrin-ferment is a nucleoalbumin. Histon, a base consisting of protamin and albumose, is present in the nuclei of the erythrocytes of birds and in leukocytes, thymus, spleen, testicles, in combination with nuclein. It is coagulable by ammonia, not by boiling, and can be extracted by means of dilute acids. Reticulin, the ground-substance of reticular connective tissue, is a related body. It contains phosphorus and sulphur, is indigestible and insoluble, and on heating with alkalies splits off the phosphorus-containing group, and is then soluble with difficulty. With hydrochloric acid it splits off amidovalerianic acid (but no tyrosin). Plastin is similar to nuclein and occurs in the nuclei and in the protoplasm of spermatozoa. It is formed in the process of peptic digestion, and is insoluble in sodium carbonate as well as in hydrochloric acid 4 to 3 of water. THE ALBUMINOID BODIES. These resemble the true albuminous bodies with reference to their composition and source. They are uncrystallizable ; some of them are free of sulphur; while most cannot be prepared in an ash-free state. Their reactions and decomposi- tion-products resemble those of the albuminous bodies. Some of them yield, in addition to much leucin and tyrosin, also glycin and alanin (amidopropionic acid), although in physiological, chemical and physical respects they exhibit considerable differences from albuminous bodies. They occur in the tissues both as organized constituents as well as in liquid form. Whether they are formed by oxidation from the albuminous bodies or by synthesis is not known. They are in part indigestible, in part digestible, although the products of their digestion can replace the decomposed albumin in the body not at all or but incompletely. They are THE ALBUMINOID BODIES. 461 contained principally in the connecting and protecting structures of the body. They can enter into combination with acids or alkalies. 1. Keratin is present in all horny and epidermal structures. It is soluble only in boiling caustic alkalies, while it swells in cold alkalies and in concentrated acetic acid. It contains from 2 to 5 per cent, of sulphur, a large part of which can be split off by alkalies. It is indigestible; decomposed by hydrolysis it yields 10 per cent, of leucin and 3.6 per cent, of tyrosin. Neurokeratin is described on p. 627. 2. Fibroin is soluble in strong alkalies and mineral acids, as well as in cupric- ammonium sulphate. Boiled with sulphuric acid it yields 5 per cent, of tyrosin, leucin and glycin. It is the principal ingredient of the web of insects and spiders. By long boiling silk-gelatin (sericiri) is obtained from silk. This body is richer in oxygen and water than fibroin. Treated with sulphuric acid it yields, in addition to leucin and tyrosin, also serin, a crystalline amidoacid. 3. Spongin, a body resembling fibroin, and derived from sponges, yields leucin and glycin as decomposition-products. 4. Elastin, the ground-substance of all elastic tissue-elements, is soluble only when boiled in concentrated potassium hydroxid. It yields from 36 to 45 per cent, of leucin, together with one-half per cent, of tyrosin. It yields the reactions of albumin and its decomposition-products. It contains sulphur only in loose combination. It is peptonized by trypsin, but not by the gastric juice. 5 . Glutin or bone-gelatin can be prepared from all connective or gelatin-yielding substances (which contain collagen) in the form of gelatin by boiling with water. This gelatin on cooling forms a jelly. Collagen is soluble by boiling with acids or alkalies. Glut in is strongly levorotatory. It is transformed by long boiling and digestion into a peptone-like state, in which it does not become gelatinous. A glutin-like body is present in leukemic blood and in splenic juice. Glycin, leucin and ammonia, but no tyrosin, result on hydrolytic decomposition. Glutin contains 0.7 per cent, of sulphur. 6. Chondrin or cartilage-gelatin is obtained by boiling hyaline cartilage. It becomes gelatinous in the cold. It is precipitated by acetic acid and by small amounts of mineral acids. It is dissolved in an excess of the latter as well as by neutral salts. The true characteristic substance of hyaline and elastic cartilage is a mono- basic acid, namely, chondroitin (Ci 8 H 27 Npi 4 ) , which as an ethereal sulphate, namely, as chondroitin-sulphuric acid, is contained in cartilage. This acid is present in cartilage only in exceedingly loose combination with albuminous or gelatinous substances. Alkalies separate the albuminous bodies from the chondroitin-sul- phuric acid by forming alkaline salts with the latter. The chondrin (of the earlier writers) is a gelatinizing solution consisting of a mixture of ordinary gelatin and the last-mentioned chondroitin-sulphates of the alkalies. It can, therefore, be prepared artificially from gelatin and potassium or sodium chondroitin-sulphate. True hyaline cartilage is, therefore, distinguished from (gelatin-yielding) osseous cartilage by the circumstance that the ground-substance of the former contains chondroitin-sulphates. On decomposition of chondroitin (as well as of chitin) glycosamin (C 6 H n O 5 NH 2 ) is formed, the latter on treatment with nitrous acid being transformed into glucose an example of the manner in which non-nitrogenous carbohydrates may be derived from nitrogenous albuminous bodies. 7. The hydrolytic ferments, also designated enzymes (in order to distinguish them from the organized ferments, for example yeast and bacteria). The charac- teristic of all organized ferments is that they are active only in the presence of water and in such a manner that they cause a decomposition of the body upon which they act as a result of which the latter takes up water. All of the ferments likewise decompose hydrogen dioxid into water and oxygen. Their activity is greatest at a temperature between 30 and 35 C. They are destroyed by boiling. In the dry state they may tolerate exposure to a temperature of 100 C. without attenuation. The addition in considerable amount of antiseptics that destroy lower organisms does not check their activity. During periods of protracted in- activity their solutions undergo destruction in greater or lesser degree. The fol- lowing hydrolytic ferments are distinguished: (a) Sugar-forming ferments in the saliva, the pancreatic juice, the intestinal juice, the bile, the blood, the lymph, the chyle, the liver, the urine, the milk, and invertin in the intestinal juice. Almost all dead tissues, organic fluids, and even albuminous bodies, may 462 FATS. exert a feeble diastatic action. Diastatic ferment is found also in grain and leguminous fruits, in hay and other vegetable foods. (6) Proteolytic ferments: In the gastric juice (pepsin), the muscles, also in germinated seeds, for example vetches, malted barley, and in the myxomycetes; in the pancreatic juice (trypsin), the intestinal juice, the urine. Pepsin and trypsin diffuse through membranes like peptone. (c) Fat-splitting ferments: in the pancreatic juice. (d) Milk-coagulating -ferments: in the stomach, the pancreatic juice, the urine. NITROGENOUS GLUCOSIDS. The following nitrogenous glucosids, which on hydrolytic treatment take up water and are decomposed into sugar and other atom-groups, may be considered here: Cerebrin, C 57 H 110 N 2 O 25 . Protagon in the medullary substance of nerves (C 66 . 30 N 2 . 39 H 10 . 69 P 1 . 068 per cent.) Chitin, 2 (C 15 H 26 N 2 O 10 ) , a nitrogenous glucosid or amin of a carbohydrate in the cutaneous covering of all arthropods, also in the intestine and the trachea of these animals; soluble in concentrated hydrochloric or nitric acid. The hyalin of the bladder-worms is closely allied to chitin. Among the glucosids of the vegetable kingdom are also solanin, amygdalin and salicin. NITROGENOUS PIGMENTS. These are of unknown constitution and occur only in animals. In all proba- bility they are all derivatives of hemoglobin. They are: (i) Hematin and hema- toidin. (2) The biliary pigments. (3) The urinary pigments. (4) Melanin or the black pigment contained partly in epithelial cells (choroid, iris, deep epidermal cells in colored races) , partly in connective-tissue corpuscles (lamina fusca of the choroid) , in hairs and in pathological neoplasms. Schmiedeberg produced melanin by boiling albumin for a long time with concentrated mineral waters. The melanin >repared from a melanosarcoma had the following composition: C 68 H 64 N 10 SO 26 + ORGANIC NON-NITROGENOUS ACIDS. The fatty acids, constructed according to the formula C n H 2n - 1 O(OH) f are present in the body in part free, in part combined. In the free state the volatile fatty acids are found in decomposing cutaneous secretions (sweat) , also in the large intestine. In combination, acetic acid and caproic acid will appear as amido-combinations in glycin (amido-acetic acid) and leucin (amido-caproic acid) . Particularly, however, the fatty acids are combined with glycerin to form neutral fats, from which, in the process of pancreatic digestion, the fatty acids are again decomposed. The acids of the acrylic-acid series, constructed according to the formula C n H 2 n- 3 (HO), yield the animal organism but one acid, namely oleic acid. This, also, forms with glycerin the neutral fat, olein. It will be advisable at this point to discuss the neutral fats, in the formation of which both the fatty acids and oleic acid are utilized. THE FATS. The fats occur abundantly in the animal body, but probably also in all plants, in the latter particularly in the seeds (nuts, almond, cocoanut, poppy), less commonly in the pericarp (olive) , or in the root. They are obtained by expression, by melting or by extraction with ether or boiling alcohol. They contain a smaller amount of oxygen than the carbohydrates. On paper they produce characteristic fat-spots; agitated with colloidal substances they yield an emulsion. If neutral fats are superheated with water or are heated with certain ferments or are permitted to undergo decomposition, they take up water and break up into glycerin and free fatty acids, of which the latter, if volatile, diffuse a rancid odor. Treated with caustic alkalies they likewise take up water and are decomposed into glycerin and fatty acids. The fatty acids form salt-like combinations (soaps) with the alkali, while the glycerin is set free. The soap-solutions in turn dissolve fats. Glycerin, a triatomic alcohol, C 3 H 5 (OH) 3 , combines (i) with the following mono- basic fatty acids: FATS. 463 Formic acid, CH 2 O 2 , Acetic acid, C 2 H 4 O 2 i. 2. , 242 , 3. Propionic acid, C 3 H 6 O 2 , 4. Butyric acids, C 4 H 8 O 2 , 5. 6. 7. 8. 9. 10. Valerianic acid, C 5 Hi O 2 , Caproic acids, C 6 H 12 O 2 , Enanthylic acids, C 7 H 14 O 2 , Caprylic acids, C 8 H 16 O 2 , Pelargonic acid, C 9 H 18 O 2 , Capric acid, C ]0 H 20 O 2 , Undecylic acids, CnH^O^ 12. Laurostearic acid, C 12 H 24 O fl , A j J. \SL \>CL*~L\^^y iiv* CU^XVl0f V^iciJ. 1 6. Palmitic acids, C, 6 H 32 O 2 , 17. Margaric acids, C 17 H 34 O 2 , 1 8. Stearic acids, C 18 H 36 O 2 , 19. Arachinic acid, C^H^Oj, 20. Hyenic acid, C 25 H 50 O 2 , 21. Cerotic acid, C 27 H 34 O 2 , 22. Melissic acid, C 30 H 60 O 2 , etc. The acids form an homologous series according to the formula C n H 2n - 1 O(pH). With each additional CH 2 the boiling-point is raised 19. The acids containing a larger amount of carbon are consistent and do not volatilize; those containing a lesser amount of carbon (to 10 inclusive) are oleaginous and volatile, with a pungent acid taste and a rancid odor. The earlier may be produced from the later in the series by oxidation, CH 2 disappearing, with the formation of CO 2 and H 2 O: for example, butyric acid results from propionic acid. Human and animal fat contain 16 and 18, in smaller amount and inconstantly 14, 12, 6, 8, 10, 4. Some are contained in the sweat and in the milk. Many develop from albumin and gelatin in the process of putrefaction. The majority, with the ex- ception of those from 19 to 22, are present in the contents of the large intestine. 2. In addition, glycerin combines with the monobasic oleic acids, which like- wise form a series and stand in an intimate relation to the fatty acids. Their general formula is C n H 2n - 3 O(OH) ; they all thus possess 2H less than the cor- responding members of the fatty-acid series. By suitable procedures the cor- responding fatty acids can be obtained from the oleic acids, and conversely oleic acids develop from the corresponding fatty acids. Oleic acid (elaic acid) , C }8 H 34 O 2 , is the only member found in the organism; combined with glycerin it yields fluid olein. The fat in the new-born contains more glycerids of palmitic and stearic acids than that of the adult, which contains more glycerids of oleic acid. In addition, oleic acid occurs in combination with alkalies (in soaps), and, like a number of fatty acids, in the lecithins. Lecithin is considered as a glycero- phosphate of neurin, in which two atoms of H in the radicle of glycero-phosphoric acid are replaced by two atoms of stearic, palmitic, or oleic acid. If barium hydrate is added to lecithins, insoluble barium stearate or oleate or palmitate + oleate is produced, together with neurin in solution and barium glycero-phos- phate. There appear to be different lecithins, of which those combined with the stearic-acid and that with the palmitic-acid + oleic-acid radicle are the most frequent. Lecithin is present in the blood-corpuscles, in larger amount in the semen, in the yolk of birds, in the nervous tissue, in traces in all animal cells. Neurin also is a constant constituent of bacteria and of the seeds of vetch and peas. The neutral fats, the glycerids of the fatty acids and of oleic acid, are triple ethers of the triatomic alcohol, glycerin. Fat in the ordinary sense of the word consists of palmitin (with a melting-point of 62), stearin (71.5), olein (o). Related to the neutral fats is glycero-phosphoric acid, an acid glycerin-ether, resulting from the combination of glycerin with phosphoric acid, with the giving off of i molecule of water C 3 H fl PO 6 ; it is a product of the decomposition of lecithin. Spermaceti (cetaceum) , obtained from the cranial cavity of certain whales, contains principally palmitic-acid cetyl-ether. 3. The glycolic acids, acids of the lactic-acid series, are constructed according to the formula C n H n - 2 O(OH) 2 . They result from the fatty acids by oxidation, if i atom of H in the fatty acids is replaced by OH (hydroxyl). Conversely also fatty acids can be obtained from the glycolic acids. Those fatty acids that (from propionic acid downward) contain more than 2 atoms of C may form various isomeric glycolic acids, in accordance with the C-atom in which the other hydroxl- group enters. There occur in the body (a) Carbonic acid, hydrooxyformic acid, CO(OH) 2 , in this form, however, forming only salts. Free carbonic acid is the anhydrid, namely CO 2 . (6) Glycolic acid, oxyacetic acid, C 2 H 2 O(OH) 2 , does not occur in the body in the free state. A combination of this, glycin glycocol, amido-acetic acid, gelatin-sugaroccurs as a conjugate acid, namely as glycocholic acid in the bile and as hippuric acid in the urine. Glycin exists in gelatin in complex combination. (c) Lactic acid, oxypropionic acid, C 3 H 4 O(OH) 2 , is contained in the body in two isomeric forms: (i) Ethylidene lactic acid, which occurs in two modifica- 464 THE ALCOHOLS. tions, namely as dextrorotatory sarcolactic acid, paralactic acid, a metabolic product of muscle and also in the thymus and thyroid glands ; it develops also from the action of bacteria on grape-sugar, and as ordinary optically inactive or fermentation-lactic-acid, which is present in the gastric juice, in sour milk, sour- crout, sour pickles, and can also be obtained from sugar by fermentation. (2) The isomer ethyl ene lactic acid is likewise present in muscle in small amounts. (rf) Leucic acid, oxycaproic acid, C 6 H 12 O 3 , does not occur independently, but only as a derivative, namely as leucin, amidocaproic acid, as a metabolic product in. certain tissues, as well as a product of pancreatic digestion. By treatment with nitrous acid leucic acid can be produced from leucin, and glycolic acid from glycin. 4 . A cids of the oxalic-acid or succinic-acid series , with the formula C n H 2n - 4 O 2 (O H) 2 , dibasic acids, which develop from fatty acids and glycolic acids as completed oxidation-products by taking up oxygen and giving off water. Their development from bodies rich in carbon, particularly fats, carbohydrates and proteids, is, there- fore, noteworthy. (a) Oxalic acid, C 2 O 2 (OH) 2 , results by oxidation from glycol, glycin, cellulose, sugar, starch, glycerin and many vegetable acids, and occurs normally in the urine in combination with calcium. (6) Succinic acid, C 4 H 4 O 2 (OH) 2 , has been found by some in small amounts in dead animal tissues and fluids, urine, echinococcus-fluid, hydrocephalus-fluid, hydrocele-fluid. It is present in large amount in the urine of the dog after a diet of fat and meat, in the urine of the rabbit when fed with carrots. It is gen- erated by micro-organisms and is wanting in fresh, living tissues. It develops in small amounts in the process of alcoholic fermentation. 5. The cholalic acids are present in bile and in the intestine. 6. Aromatic acids, containing the benzol-nucleus: benzoic acid (phenylformic acid) occurs in the urine in conjunction with glycin as hippuric acid. THE ALCOHOLS. Alcohols are bodies that develop from carbohydrates by the substitution of hydroxyl (HO) for one or more atoms of hydrogen. They can also be viewed as water, }O, in which half of the hydrogen is replaced by a CH-combination. Thus, for instance, C 2 H 6 , ethyl hydrid, is transformed into C2 g 5 }O, ethyl-alcohol. (a) Cholesterin, cJ^j-O, is a levorotatory alcohol that occurs in blood, yolk' brain and bile, and," besides, quite generally in vegetable cells. It is present also in tissues of man and animals containing keratin. Liebreich considers choles- terin as a necrobiotic fat. By oxidation cholesteric acid (C 8 H 10 O 5 ) is developed from cholesterin, appearing also as an oxidation-product of cholic acid. ( OFT (6) Glycerin, C,H,O^ OH, is considered as a triatomic alcohol. It occurs in I OH combination with fatty and oleic acids in neutral fats. It is formed in the process of pancreatic digestion by decomposition of the neutral fats. It is developed in small amount as a result of the fermentation of fats in the intestine, as well as in the process of alcoholic fermentation. (c) Phenol (phenylic acid, carbolic acid, oxybenzol). (d) Pyrocatechin (dioxybenzol) . (e) The sugars may be considered advantageously in connection with the alcohols, as they behave like polyatomic alcohols. Their exact constitution is as yet unknown. The sugars form, together with a series of closely related bodies, the large group of carbohydrates, which will be considered collectively. Although many of these do not occur in the animal body, their consideration is justified by the fact that they occur largely as constituents of vegetable food. THE CARBOHYDRATES. These bodies occur in the animal and vegetable kingdoms and have received their designation because they contain in their molecules, in addition to at least six atoms of C, the atoms of H and O always in the proportions present in water, namely, H 2 O. All are solid, chemically indifferent, without odor. They either have a sweet taste (sugars) or may at least be readily transformed into sugar by the action of dilute acids. They deflect the ray of polarized light either to THE CARBOHYDRATES. 465 the right or to the left. Heated dry they give off the odor of caramel. They stain red with thymol and sulphuric acid. According to their constitution, they may be considered as fatty bodies, as hexatomic alcohol in which 2 atoms of H are wanting. In small amounts the carbohydrates are constituents of almost all animal tissues. In the presence of special nutritive disturbances decomposition of complex organic constituents of the viscera appears to take place. Nitrogenous products that are readily decomposed into urea are split off from the albuminates, and in addition to these the non-nitrogenous portion appears as carbohydrate. The formation of carbohydrates (sugar) from fats occurs in the germination of seeds containing oil, with the taking up of oxygen. The carbohydrates can be divided into the following groups : 1. The monosaccharids or glucoses, which contain only one molecule of simple sugar: C 6 H 12 O 6 . i. Grape-sugar (glucose, dextrose, lump-sugar, starch-sugar, liver- sugar or urinary sugar) has been produced synthetically by E. Fischer. It occurs in the animal body in small amounts in the blood, chyle, muscle, liver, urine; in large amounts in the urine in cases of diabetes mellitus. It is formed in the process of digestion by diastatic ferments from other carbohydrates. In the vegetable kingdom it is distributed in the sweet juices of many fruits and flowers, and thence into honey. It is formed from cane-sugar, maltose, dextrin, glycogen and starch on boiling with dilute acids. It crystallizes in cauliflower-like, warty masses, with one molecule of water of crystallization, combines with bases, salts, acids and alcohols, but is readily decomposed by bases. It exerts a reducing action on many metallic oxids. Phenylglucosazone melts at a temperature of 204 C. As a result of its oxidation there develop first the monobasic glyconic acid and then the monobasic glucic acid. A fresh solution has a rotatory power of +106, which falls to +56. On fermentation with yeast it is decomposed into alcohol and carbon dioxid; by putrefactive bacteria it is broken up into two molecules of lactic acid. The qualitative and quantitative estimation of grape-sugar is discussed on pp. 267, 268, and 501. In alcoholic solution it enters into almost insoluble combinations with calcium, barium or potassium; also with sodium chlorid it crystallizes into a combination. 2. Galactose is formed by hydrolytic decomposition of milk-sugar (lactose), but also by hydrolysis of gum and mucoid substances; and as a decomposition- product of the glucosid, cerebrin. It forms needles and plates, soluble in water, is dextrorotatory + 88.08 and fermentable and yields the reactions of dextrose. Its phenylosazone melts at 193 C. When oxidized it forms galactonic acid and later mucic acid. 3. Levulose (levorotatory fruit-sugar, invert-sugar or mucous sugar) is formed from inulin by the action of acids together with levulin, which is the analogue of dex- trin. It occurs in the acid juices of some fruits and in honey as a colorless syrup, crys- tallizable with difficulty, fermentable with greater difficulty, insoluble in cold alcohol, with a rotatory power of 106. It reduces like dextrose and has the same osazone. It is formed normally in the intestine and is rarely found abnor- mally in the urine. II. Disaccharids or saccharoses contain two molecules of simple sugar, and hav- ing the formula C 12 H 22 O U , are the anhydrids of the members of the first division. 1. Milk-sugar (lactose = dextrose + galactose) occurs only in milk, crystal- lizes in crusts, with i molecule of water, from whey evaporated to a syrupy con- sistence, is dextrorotatory +52.5, soluble with greater difficulty than grape-sugar in water and particularly in alcohol. On boiling with dilute mineral acids it is decomposed into galactose and dextrose; it can be transformed directly into lactic acid only by fermentation, and the resulting galactose is, however, sus- ceptible of alcoholic fermentation with yeast (preparation of koumiss). Its quan- titative estimation is discussed on p. 422. It occurs rarely in the urine. Lacto- sazoiie melts at 200 C. 2. Maltose (malt-sugar), C 12 H 22 O 12 + H 2 O, contains one molecule of water less than two molecules of grape-sugar (C 12 H 24 O 12 ) and results in the diastatic decomposi- tion of starch. It is soluble in alcohol", but is precipitated from an alcoholic solution by ether in the form of needles (dextrose is not). It is dextrorotatory 138.4 and crystallizable, and 100 parts reduce equally with 66 of dextrose. Dextrose reduces cupric acetate, while maltose does not. Maltosazone melts at 208 C. Isomaltose is not susceptible of fermentation. 3. Saccharose (cane-sugar or beet-sugar = dextrose + fruit-sugar) is present in cane-sugar and a number of plants, but it does not reduce copper. It is soluble in alcohol with difficulty, is dextrorotatory and not fermentable. In the intestine, and also when boiled with dilute acids, it is transformed into a mixture of glucose 30 466 THE CARBOHYDRATES. and levulose. Oxidized with nitric acid it is decomposed into glucic acid and oxalic acid. III. Polysaccharids or amyloses, result, as anhydrids of members of the first division, from the union of many molecules of the monosaccharids. Many of them do not undergo fermentation. They yield colloid solutions, do not diffuse and do not crystallize. 1. Glycogen, with a rotatory power of +211, devoid of reducing action, occurs in the liver, the muscles, many embryonal tissues, the fetal membranes, the rudimentary embryo of the chick and in part in normal and pathological epithelium. It is present in small amounts in many organs: testicle, lung, skin, and in pus and inflammatory foci. It has been found in considerable amount in the body of the diabetic, in the brain, the pancreas, and cartilage. It occurs also in oysters and other molluscs, but it may be present in the cells of all of the tissues and of all classes of animals. Errera found glycogen in yeast. 2. Dextrin is dextrorotatory +138, forms a viscid solution with water, from which it is precipitable by alcohol and acetic acid, and is discolored feebly red by iodin. It results from scorched starch (and is therefore abundant in bread- crusts) through the action of dilute acids, and in the body through the action of ferments. It is formed from cellulose by treatment with dilute sulphuric acid. It occurs also in beer. In the vegetable kingdom it is present in most vegetable juices. 3. Starch is present in the mealy portion of many vegetables, partly con- sisting of organized granules in layers forming within the vegetable cells, with a generally excentric nucleus, and partly, though less commonly, occurring unformed in vegetables. The diameter of the starch-granule varies considerably in different plants. It is, for instance, from 0.14 to 0.18 mm. in the potato and only 0.004 mm. in the seed of the red beet. In water at a temperature of 72 C. it swells as a paste. It is stained blue by iodin only in the cold. The starch-granules contain further always more or less cellulose, as well as a body stained red by iodin (erythrogranulose) . The transformation of starch and glycogen takes place through the action of the saliva, the pancreatic and the intestinal juice; both are transformed into dextrose by dilute sulphuric acid. 4. Gum, C 10 H 20 O 10 , occurs in man in organs containing mucus, such as the salivary glands, the mucoid tissues, the lungs, and in bile, occasionally in albuminous fluids, and in small amounts in the urine. It is susceptible of fermentation and is decomposed by boiling with dilute acids into a body reducing copper oxid. In the vegetable kingdom gum is found in the juices particularly of acacias and mimosas, partly soluble in water (arabin), partly swelling up like mucus (bassorin). It is precipitated by alcohol. Wood-gum (pentosan, C 5 H S O 4 ) occurs abundantly in fibrous vegetable matters consumed by herbivora as food. On heating with dilute acids there result by hydration pentoses, in the same way as dextrose is formed from starch. There are two pentosans: xylan, which yields xylose, and araban, from which arabinose results. Pentosan results from the oxidation of cellulose and starch, i atom of C being transformed into CO 2 . 5. Inulin, a crystalline powder present in the root of chicory and dandelion, and in the bulbs of dahlia variabilis, is not stained blue by iodin. 6. Lichenin, lichen-starch, the intercellular substance of lichens, especially of Iceland moss (cetraria Icelandica), and of algae. It can be transformed into glucose by dilute sulphuric acid. 7. Cellulose, C 6 H 10 O 5 , the cellular tissue of all vegetables, is found also in the integument of tunicates, the exoskeleton of arthropods and the skin of snakes. It is soluble only in ammoniated cupric oxid and is colored blue by sulphuric acid and iodin. On boiling with dilute sulphuric acid dextrin and glucose are formed. It is transformed (cotton) by concentrated nitric acid mixed with sulphuric acid into nitro-cellulose (gun-cotton, C 6 H 7 (NO 2 ) 3 p 5) ), which, dissolved in a mixture of ether and alcohol, forms collodion. Tunicin, a body similar to cellulose, occurs in the integument of tunicates (molluscs). Cellulose is dissolved in the intestine of herbivora with the aid of bacteria. For the sake of completeness, inosite, C 6 H 12 O 6 , hexahydrohexaoxybenzol, muscle-sugar, phaseomannite, bean-sugar, may be discussed at this point. This is not a true sugar, but it has a sweet taste. It occurs in the muscles, the lungs, the liver, the spleen, the kidneys, the brain of the ox, and the kidneys of man; pathologically in the urine and in echinococcus-fluid. It is widely distributed in the vegetable kingdom, especially in beans (Leguminosae) and in grape-juice. It is optically inactive, generally crystallizes like cauliflower, with two molecules of water, in long monoclinic crystals, insoluble in alcohol or ether; it does not re- AMMONIA-DERIVATIVES AND THEIR COMBINATIONS. 467 spond to Trommer's test and is susceptible only of sarcolactic-acid fermentation. Evaporated to dryness with nitric acid, then with ammonia and calcium chlorid, it leaves a rosy-red stain. AMMONIA-DERIVATIVES AND THEIR COMBINATIONS. The ammonia-derivatives are products of proteids, decomposition-products of the tissue-metamorphosis of proteids. 1. Amins, that is compound ammonias, which may be derived from ammonia (NH 3 ) or from ammonium hydroxid (H 4 N, OH) by replacing one or all of the atoms of H by carbohydrate-groups (alcohol-radicles) . The amins derived from a single molecule of ammonia are designated monamins. Among these are methylamin, H IN, and trym'ethalamin, CH^N, known only as decomposition-products of CH 3 } CH 3 f cholin (neurin) and of kreatin. Neurin occurs in lecithin in complex combination. The lecithins are described on p. 463 and the diamins are discussed on p. 305. 2. Amids, that is derivatives of acids in which NH 2 is substituted for the hydroxyl (HO) of the acids. Urea, CO(NH 2 ) 2 , the diamid of CO 2 is the principal end-product of the tissue-metamorphosis of the nitrogenous constituents of the body. Carbon dioxid containing water is CO(OH) 2 , in which both OH-atoms are replaced by NH 2 , thus CO(NH 2 ) 2 . 3. Amido-acids, that is nitrogenous combinations exhibiting partly the character of an acid, and partly that of a feeble base, in which H-atoms of the acid-radicle are replaced by NH 2 or substituted ammonia-groups. (a) Glycin (amido-acetic acid, glycocol, gelatin-sugar) results on boiling gelatin with dilute sulphuric acid. It is present in the cornea, which contains, besides, chondrin. It has a sweet taste (gelatin-sugar), behaves like a feeble acid, but unites also as an amin-base with acids. It occurs as glycin + benzoic acid = hippuric- acid in the urine (it has also been prepared artificially) , and as glycin + cholic acid = glycocholic acid in the bile. (6) Leucin (amidocaproic acid) has been found pathologically in pus and in the atheromatous matter of sebaceous cysts, generally in combination with tyrosin. (c) Serin (amidolactic acid) is obtained from silk- gelatin, (d) Blood-alinin (amidovalerianic acid) . (e) A spartic acid (amidosuccinic acid) . (/) Glutamic acid (amidopyrotartaric acid) is obtained in the decomposition of albuminates. Aspartic acid can be obtained from asparagin by boiling with acids and the splitting off of ammonia. Asparagin is formed largely in the vegetable kingdom from albumin and has been prepared artificially, while in the animal body it is transformed into urea and uric acid, (g) Cystin (amidolactic acid), in which O is replaced by S, is strongly levorotatory. (h) Taurin (amido-ethyl- sulphuric acid) occurs, besides in a number of glands, particularly in combination with cholic acid as taurocholic acid in bile. It has also been prepared artificially. (i) Tyrosin (paraoxyphenylamidopropionic acid, prepared synthetically) occurs together with leucin in the presence of pancreatic digestion. It may occur patho- logically in the urine. It is abundant in dahlia-bulbs. There are related to the amido-acids further: (a) Kreatin, methylguanidin- acetic acid, CH 9 N 3 O 2 , which is present in muscle, brain, blood, and' urine, and has been prepared artificially. Boiled with baryta-water it takes up water and is decomposed into urea; (6) Sarcosin (C 3 H 7 NO 2 , methylamido-acetic acid). When boiled with water or heated with strong acids in the presence of decomposing substances kreatin is transformed into kreatinin with the loss of water; kreatinin occurs in the urine. This strong base can be retransformed into kreatin by the action of alkalies. 4. Ammonia-derivatives in Part of Unknown Constitution. Uric acid. Allan- loin results from the oxidation of uric acid by means of potassium permanganate. It has been found, together with guanin and sarcin, also in the buds of Platanaceae. Cyanuric acid has been found in dog's urine. Inosinic acid is present in muscle. Guanin (C 5 H 5 N 5 O), together with adenin, xanthin and hypoxanthin, a decomposi- tion-product of nuclein, occurs in traces in normal blood, in larger amount in leukemic blood, and in considerable amount in embryonal muscle, as well as in the liver, the spleen and the pancreas. It occurs, pathologically, in rapidly growing neoplasms rich in nuclei, and in the muscles of swine suffering from guanin-gout. It is transformed by nitrous acid into xanthin, by oxidation into urea and when fed to animals it increases the elimination of urea. It occurs, further, in guano, in the excrement of spiders, in the skin of amphibia and reptiles, in the silver gloss of some fish (for example the herring) . Hypoxanthin or sarcin 468 HISTORICAL. in association with xanthin occurs in many organs and in urine. Kossel suc- ceeded in preparing hypoxanthin from nuclein b)^ prolonged boiling. It can be obtained from fibrin by putrefaction and the action of gastric and pancreatic juice. Xanthin can be produced from hypoxanthin by oxidation and is con- vertible into caffein. Xanthin and guanin have been produced synthetically by Gautier. Paraxanthin and heteroxanthin occur in the urine; carnin, which re- sembles them, in meat. An intermediate stage between nuclein. and hypoxanthin is represented by the adenin (C 3 H 5 N 5 ) of Kossel, which has _ been found in the spleen, the pancreas, the thymus, the seminal fluid, and also in tea and in yeast. It appears to occur as an amorphous powder, or in six-sided columns disintegrating in the air, and as a decomposition-product of nuclein in all animal and vegeta- ble cell-tissues. AROMATIC BODIES. i. M anatomic phenols: (a) The phenol (hydroxl or benzol) in the intestine; phenylsulphuric acid in the urine. (b) Kresol in the form of orthokresol, meta- kresol and parakresol combines with sulphuric acid in the urine. (2) Diatomic phenols: (a) Pyrocatechin combined with sulphuric acid in the urine. (3)^ Aro- matic oxy acids: (a) Hydroparacumanc acid; (6) Paroxyphenylacetic acid in the urine. (4) Substituted carbohydrates: (a) Indol (also prepared artificially) and (b) skatol both occur in the intestine and combined with sulphuric acid in the urine. Stoehr has prepared skatol artificially by distillation of strychnin with calcium. HISTORICAL. According to Aristotle the body requires food for three purposes, namely for growth, for the generation of heat and to compensate for loss from the body. The generation of heat was thought to take place in the heart by a process of concoction, the heat being carried with the blood to all parts of the body, while the act of respiration was considered as a means for dissipating the excess of heat generated in the process of combustion. In a somewhat modified form also Galen held this view. According to him the metabolism is comparable to the conception of a lamp, the blood representing, to a certain degree, the oil, the heart the wick, and, finally, the lungs the draft. According to the view of the iatrochemical school, metabolism takes place in the body in the form of fermentative processes in which the substances introduced are decomposed in conjunction with the bodily juices. There thus result refined, useful juices, and fermentative waste products intended for excretion. Since the middle of the seventeenth century knowledge of the metabolic processes has progressed hand in hand with the devel- opment of chemistry. A. v. Haller ascribed the heat to chemical processes. He believed that the nourishment must make good to the body the constant loss of excrementitious matter. Anabolism takes place through a lymphatic fluid, which is poured out for the reconstruction of the used-up animal fibers between the latter. Mayow believed in 1679 that metabolism was essentially a process of combustion, the blood becoming bright red in the lungs. After the discovery of oxygen Lavoisier formulated the theory of combustion in the lungs, in which he believed carbon dioxid and water were formed. He compared the relatively slow course of physiological combustion with the heating of dung that takes place at a lower temperature. Mitscherlich compared the metabolic processes in the living body directly with putrefactive phenomena. Magendie first pointed out the difference between nitrogenous and non-nitrogenous foods and showed that the latter alone are not capable of sustaining life. Also gelatin alone is insufficient for this purpose. His results were less precise with respect to the nutritive value of albuminates, which he nevertheless gave foremost rank, and among which he was willing to recognize only meat as adequate as nutritive material. The greatest advance in the principles of nutrition is due to J. Liebig, who laid the foundation of the present knowledge of metabolism. According to his view food-stuffs subserve two purposes, namely as plastic, for the growth of the body, and, as respiratory, for the generation of heat. The former includes espe- cially the albuminates, the latter especially the non-nitrogenous carbohydrates and fats. Among recent investigators the Munich school deserves especial mention as advancing knowledge: v. Bischoff, v. Pettenkofer, v. Voit and others. Most recently Pfliiger has made important contributions. THE SECRETION OF URINE. 469 THE SECRETION OF URINE. STRUCTURE OF THE KIDNEY. The kidneys are compound tubular glands (Fig. 142). All of the urinary tubules arise within the cortex of the kidney from Bow- man's capsules, which are globular in shape, measure from 200 to 300 fi in diameter, are constituted of endothelioid cells (k), and whose inner surface is lined with a single layer of epithelial cells (Fig. 142, II). In the interior of the capsule lies the convolution of vessels known as the glomerulus or Malpighian body. Each capsule passes by means of a narrowed portion into the convoluted urinary tubule, which has a diameter of 45 p (I, x). This possesses a membrana propri'a constituted of extremely fine fibers and passes through the cortical structure in a devious course. It is lined by characteristic epithelium, the cells contain- ing a turbid protoplasm that swells readily and is occasionally filled with fat-globules. That portion of the protoplasm which. is directed toward the rela- tively narrow lumen of the tubule contains a distinct globular nucleus, while the portion adjacent to the membrana propria, and different also chemically, presents a fibrillated appearance, as if constituted of rods. Where the rods are in direct contact with the membrane they diverge like the bristles of a brush pressed against a surface. The free extremities of the rods of adjacent cells touch one another, so that the attached surface of the cells acquires an irregular radiating appearance. When secretion takes place the free surface has a brush- like margin. Landauer describes the cells of the convoluted tubules and of the wider portion of Henle's loop as provided with lateral folds (and not with the rod-like structure) , by means of which adjacent cells are brought in direct contact with one another. At the junction of the medullary and the cortical tissue the convoluted tubule becomes suddenly constricted and passes over as Henle's loop in the form of an elongated arch into the medullary structure (t, t). A distinction is made in the loop between the small descending limb, with a relatively large lumen (14 //) and clear, flat epithelium arranged in alternating order and bulged out at the middle by its nucleus (IV, S), and the wider, ascending limb. The transition from the one to the other takes place in man, as a rule, in the lowermost portion of the descending limb. The ascending limb becomes dilated to a diameter of from 20 //. to 26 u, its lumen is relatively large and its epithelium is essentially the same as that of the convoluted tubules, except that the rods are shorter. Where the ascending limb penetrates into the cortical structure the canal at first becomes smaller again. It then passes into the intercalated portion (n, n), which has a diameter of 40 u. and in structure most nearly resembles the con- voluted tubules, than which, however, it is shorter, though lined with similar cells. After a second constriction the intercalated portions pass over into the collecting tubules (o) , which within the medullary rays projecting into the cortex have a diameter of about 45 //. In their further course downward in the papilla adjacent collecting tubules unite and form tubes having a diameter of from 200 to 300 //, the papillary ducts or excretory tubes (O), of which from 24 to 80 open at the apex of each of the 1 2 or 15 papillae (foramina papillaria or cribrum benedictum). In the lowermost and widest portion the membrana propria of the duct is surrounded and fortified by a layer of delicate connective-tissue fibers. The cells are large cylindrical epithelia, with well-defined, spherical nuclei (VI) and dip- losomata. Further upward the constricted portion of the collecting tubules is lined by low, cylindrical, rather cubical cells, with large nuclei (V) supported upon a structureless membrana propria. Within the cortical structure the cells assume an inclined position, so that they overlie one another like the shingles on a roof. In the cells of all of the urinary tubules, excepting those of the collecting tubules, a ciliated process projects from the centrosoma into the lumen of the tubule. The same peculiarity is present in the epithelium of the seminal vesicles. The Blood-vessels of the Kidney. The renal artery with its branches reaches the junction of the medullary and the cortical structure after repeated division. From this point the interlobular arteries (a) arise at equal distances apart and traverse the cortex vertically. Throughout their entire course they give off laterally the afferent vessels (i) , each of which enters into a capsule formed by the urinary tubule at a point exactly opposite to that from which the tubule 470 STRUCTURE OF THE KIDNEY. itself passes off. By breaking up into numerous capillary loops the vascular tuft or glomerulus is formed within the interior of the capsule. The glomerulus is provided toward the wall of the capsule with a covering of flat, nucleated cells FIG. 142. Structure of the Kidneys: i, the vessels and urinary tubules in semi-schematic arrangement; A, cortical capillaries; B, medullary capillaries; a, interlobular artery; i, afferent vessel; 2, efferent vessel; r e, straight arterioles; c, straight venules; v v, interlobular veins; S, origin of a stellate vein; i i, capsule enclosing a glomerulus; x x, convoluted tubule; t t, Henle's loops; n n, intercalated portion; o, collecting tubules; O, excretory duct; II, capsule and glomerulus: a, afferent vessel; e, efferent vessel; c, capillary network of the cortex; k, endothelioid structure of the capsule; h, origin of the convoluted tubule; III, rod-cells from the convoluted tubules; 2, viewed from the side (g, internal area containing the nuclei); i, viewed from the surface; IV, cellular lining of Henle's loop; V cells in collecting tubule; VI, section of the excretory duct. (Fig. 142, II), which are present also between the capillary loops of the tuft. From the loops there passes, from the center of the tuft, the efferent vessel (2), which is always of smaller size and makes its exit from the capsule close by STRUCTURE OF THE KIDNEY. 471 the side of the afferent vessel and in structure and further course resembles a small artery. Throughout the entire cortex all of the efferent vessels enter into the formation of a line capillary network (A and II, c), which surrounds the urinary tubules. Within the range of the medullary rays of the cortex the fibers of the network, in accordance with the straight course of the urinary tubules, are arranged rather longitudinally, while in the remainder of the cortex their ar- rangement is polygonal. From this capillary network of the cortex venous radicles arise to form the interlobular veins (v). These originate just beneath the fibrous capsule of the kidney from the union of the radicles of the smallest venules arranged in a stellate manner (stellulae Verheynii or stellate veins) and then pass each in the company of an interlobular artery to the junction of the medulla and the cortex. The vessels of the medullary structure arise from the straight arterioles. These either begin at the junction of the cortical and the medullary structure of the kidney as individual, direct branches (r) of the interlobular arteVies, still provided with muscular fibers, or they are formed from those efferent vessels (e) that lie adjacent to the medullary structure of the kidney. The latter are said to be un- provided with muscular fibers. Finally it is stated that a number of these vessels are formed from the union of the capillaries of the medullary rays. All of the straight arterioles, accompanying the straight urinary tubules, pass into elongated brush-like capillary bundles, which surround the urinary tubules. From these capillaries there collect throughout the entire extent of the medulla loops curving upward and downward, representing the beginning of the veins. The latter pass back toward the junction between the medullary and the cortical structure and gradually constitute the straight venules (c), which empty into the lower portion of the interlobular veins. On the papillae the capillaries of the medulla communi- cate with vascular branches in garland-like arrangement surrounding the papil- lary ducts. The vessels of the fibrous capsule of the kidney are derived in part from pene- trating branches arising from the extremity of the interlobular arteries and in part from branches of the suprarenal, phrenic and lumbar arteries, between which anastomoses take place. The capillary network is a simple mesh-arrangement. The venous radicles pass over in part into the stellate veins and in part into veins of the same name as the arteries. A number of venous radicles also pass out of the cortex. The communication between the distribution of the renal artery and other arteries in the capsule explains the fact that after ligation of the renal artery within the kidney the blood-stream may enter from the capsule. Arterial blood also is sent to the kidney and this may even give rise to a slight secretion. Lymphatics are present within the fibrous capsule as a wide-meshed network and beneath the capsule in the form of spaces of considerable size. In the parenchyma of the kidney itself the lymph is said to circulate between the urinary tubules and the blood-vessels, in tissue-spaces without walls which are found in larger number around the convoluted tubules than around the straight tubules. The spaces reach to the surface of the kidney and are dis- tributed extensively beneath the capsule. Marked distention of the lymph-spaces compresses the urinary tubules and the vessels. Large lymphatics, provided with valves, are visible at the hilus of the kidney, while others pass through the fibrous capsule, both communicating with the lymph-spaces of the capsule of the kidney. Of the nerves, branches provided with ganglia accompany the afferent vessels. Non-medullated fibers penetrate to the surface of the capsule and between the urinary tubules. It is established physiologically that motor fibers are present for the unstriated muscular fibers, also vasomotor fibers and sensory branches in the capsule and the pelvis of the kidney. The existence of vasodilator and secretory fibers is also probable. The connective tissue of the kidney forms in the papillae fibrillated, con- centric layers about the excretory ducts (VI). Further upward star-shaped cells of reticular tissue appear in addition and these are found alone in the cortex. The outer layers of the fibrous capsule of the kidney are formed of dense bundles of fibrils, while the inner layers are looser and send processes into the cortical layer. The fatty capsule of the kidney is connected with the organ itself, in part through vessels and in part through bands of connective tissue. Unstriated muscular fibers are contained in the kidney in three forms: (i) A sphincter-like layer surrounding each papilla; (2) a wide-meshed net- work on the surface of the kidney; (3) fibers that arise from the depth of the pelvis of the kidney and pass through the pyramids with the blood-vessels 472 THE URINE. H. Kostjurin found at the junction of the cortical and the medullary structure, in the dog, a layer of muscle-fibers from which bundles pass in each direction. THE URINE.* THE PHYSICAL CHARACTERS OF THE URINE. The amount of urine in men is between 1000 and 1500 cu. cm. in twenty-four hours; in women between 900 and 1200. There is a min- imum between 2 and 4 a. m., a maximum in the morning and a second maximum between 2 and 4 p. m. The amount of urine is diminished by profuse perspiration, diarrhea, thirst, food deficient in nitrogen, reduction in the general blood-pressure, after profuse hemorrhage, as a result of the action of certain poisons, such as atropin and mor- phin, and in the presence of certain diseases of the structure of the kidney. The minimum that may still be considered normal is between 400 and 500 cu. cm. The amount is increased by increase in the blood-pressure in general, or in the distribution of the renal artery alone, by copious drinking, contraction of the cutaneous vessels from the action of cold, the elimination of soluble diuretic substances, such as urea, salts, and sugar through the urine, a diet rich in nitrogen, as well as by certain medicaments, such as digitalis, juniper, squill, alcohol, etc. Carbonated beverages increase the urine in the succeeding hour. The direct influence of the nervous system upon the amount of urine is also familiar. In this category belongs the polyuria suddenly developed after nervous perturbation, as, for instance, in hysterical persons, following epileptic attacks, and also after pleasurable excitement, and finally the remarkable increase in urinary secretion after injury of the floor of the fourth ventricle of the brain. Nocturnal polyuria occurs in persons suffering from disease of the heart and the kidneys, in cachectic states and in the presence of arterio-sclerosis. Neurasthenic anuria of neurotic origin lasting from twelve to fifty-six hours is extremely rare. The urine can be measured in graduated cylinders or flasks. The specific gravity of the urine varies between 1015 and 1025. The minimum is observed after abundant ingestion of water, 1002; the maximum after profuse sweating and marked thirst, 1040. In the new- born the specific gravity falls considerably in the first few days, in conformity with the progressive increase in the amount of nourishment taken. The adult discharges per diem on the average i gram of solids through the urine for every kilogram of body-weight. The determination of the specific gravity is made, with the urine at a tem- perature of 16 C., by means of the urinometer (Fig. 144). If but a small amount of urine is obtainable and it does not sufficiently fill the urinometer-cylinder the urine is diluted with twice or thrice its volume of distilled water, and then the last two figures on the urinometer are multiplied by two or three respectively. By means of the formula of Trapp or Haeser the amount of solids contained in 1000 parts of urine can be estimated approximately from the specific gravity. Of the number indicating the specific gravity, as, for instance, 1018, the last two figures are taken, in this instance therefore 18, and multiplied by 2.33. The estimation of the total solids can be made in a more trustworthy manner by evaporating about 15 cu. cm. of urine in a weighed porcelain-dish over the water-bath and subsequent complete drying in the air-bath at a temperature of 100 C. and cooling over concentrated sulphuric acid. In this way some urea is decomposed into carbon dioxid and escaping ammonia, in consequence of which the result is some- what too low. The specific gravity depends naturally upon the amount of water in the urine. The urine of the morning (urina noctis) is most concentrated, that is, heaviest, because water is absorbed from the bladder after the urine has been * The illustrations are taken in part from Ultzmann and Hoffmann's Atlas of Urinary Sediments. THE PHYSICAL CHARACTERS OF THE URINE. 473 .... 1000 .._10U .... mo .._1080 __J040 \ present for a considerable time during sleep and the urine thus becomes in- spissated. The most dilute urine is encountered after copious drinking (urina potus). Hunger and laxatives diminish, while physical exertion increases, the amount of solids in the urine. Among pathological conditions, highly concentrated and copious urine, up to 10,000 cu. cm., is observed in cases of diabetes mellitus (p. 313), when the specific gravity may be from 1030 to 1060. Concentrated, scanty urine is encountered in the presence of fever. Simple, for instance, ner- vous, polyuria is characterized by ex- tremely dilute and copious urine, and the specific gravity may be as low as 1001. The color of the urine exhibits various gradations principally in accordance with the amount of water contained. Highly diluted urine is likely to be pale yellow in color. Urine of watery clearness has even been observed in associa- tion with sudden polyuria as, for instance, the spastic urine of the hysterical. Concentrated urine, particularly after a generous meal, lo > varies from dark yellow to brown- ish red in color. Urine of similar tint in association with fever is commonly designated high-colored. Fetal urine, as well as that passed immediately after birth, is as clear as water. Admixture of blood gives rise, in accordance with the degree of disinte- gration of hemoglobin, to a color vary- ing from red to deep brownish-red; bili- ary pigment to a deep yellowish-brown color, with an intense yellowish foam; senna, taken by the mouth, causes the urine to have a deep-red color, rhubarb a brownish-yellow color, carbolic acid a black color. Urine in a state of am- moniacal decomposition may present a dirty-blue appearance from the forma- tion of indigo. For uniform estimation of the color of the urine a urinary color- scale has been devised empirically. The urine, especially if in a state of ammoniacal decomposition, exhibits fluorescence, which disappears on addi- tion of acid, and reappears on addition of alkali. Normal urine precipitates in the course of a few hours a cloud or nubecula of vesical mucus that settles slowly. The froth of normal urine is white and it disappears rather quickly, though persist- ing for a longer time when albumin is present. Not rarely the urine contains a number of epithelial cells. Normal urine flows in a limpid stream like water. The presence of considerable amounts of sugar, albumin or mucus diminishes its fluidity. So-called chylous urine from patients in the tropics may even present a white, gelatinous appearance. The taste of urine is saline and bitter, the smell characteristically aromatic, approximating that of beef-broth, particularly after the inges- tion of roast meat. FIG. 143. Graduated cylinder and Flask for measuring the Amount of Urine. FIG. 144. Urino meter. 474 THE PHYSICAL CHARACTERS OF THE URINE. Urine in a state of ammoniacal fermentation exhibits the odor of ammonia. Of substances taken by the mouth, turpentine gives rise to the odor of violets, copaiba and cubebs to an aromatic odor, and asparagus to a disgusting odor due to methylmercaptan. Valerian, garlic and castor yield up some of their odorous constituents to the urine. The reaction of normal urine is acid from the presence of acid salts, especially acid monosodium phosphate (PO 4 H 2 Na). The latter re- sults from alkaline disodium phosphate (PO 4 HNa 2 ), uric acid, hippuric acid, sulphuric acid and carbon dioxid each taking up one atom of so- dium, so that the phosphoric acid must be displaced to form the acid salt. After a meat-diet acid potassium phosphate especially causes the acid reaction. That the urine contains no free acid is shown by the fact that no precipitate takes place on addition of sodium hyposulphite. Night-urine exhibits the highest, morning-urine the lowest degree of acidity. Sometimes the reaction of the morning- urine is alkaline. The acid reaction becomes increased after ingestion of acids, such as hydro- chloric acid and phosphoric acid; as well as of ammonium-salts, which are trans- formed in the body into nitric acid; after active muscular exercise; after a milk- diet; and pathologically in the presence of hyperacidity of the gastric juice. The absolute elimination of acid is increased by marked diuresis, while the relative elimination is diminished. The acidity of the urine is lessened and its reaction may even be rendered alkaline: (i) By the ingestion of caustic alkalies, alkaline carbonates, or alkaline salts of the vegetable acids the last being oxidized in the body into alkaline carbonates. (2) By the presence of calcium or magnesium carbonate. (3) By admixture of blood or pus of alkaline reaction. (4) By drainage of the acid gastric juice outside the body through a fistula; further, in from one to three hours after digestion, in consequence of the formation of acid in the stomach. (5) By the absorption of alkaline transudates, such as serum or blood. (6) In con- sequence of profuse secretion of sweat and hot baths. If the surface of the body is kept at a temperature of 31 C. and 30 per cent, of relative humidity, alkaline urine will be excreted in the morning-hours, on account of the fixed alkaline carbonates, while the evening-urine exhibits a strongly acid reaction. (7) The urine has rarely been observed to be alkaline in anemic persons, from deficiency of phosphoric and sulphuric acids. The reaction is tested by means of strips of violet litmus-paper, which become red when dipped in acid urine and blue in alkaline urine. In order to determine the degree of acidity of the urine it is necessary to learn the amount of sodium hydroxid required to render exactly neutral the reaction of 100 cu. cm. of urine. For this purpose a solution of sodium hydroxid is employed of which each cubic centimeter contains 0.0031 gram of sodium; i cu. cm. of this solution neutralizes exactly 0.0063 gram of oxalic acid. From a graduated buret (Fig. 145) the sodium- solution is permitted to escape drop by drop into a beaker containing 100 cu. cm. of urine, with constant stirring, until violet litmus-paper no longer becomes either red or blue. The amount of sodium-solution in cubic centimeters is read from the scale of the buret, and as each cubic centimeter corresponds to 0.0063 gram of oxalic acid, the amount of oxalic acid that is the equivalent of the acid in the 100 cu. cm. of urine can be readily estimated. The degree of acidity of the urine is therefore expressed in terms of the equivalent amount of oxalic acid that is fully neutralized by the same amount of sodium hydrate. The urine of carnivora varies in color from pale to golden yellow. It has a high specific gravity and exhibits a strongly acid reaction. The urine of herbivora has an alkaline reaction and therefore exhibits precipitates of earthy carbonates (so that it effervesces on addition of acid) and of earthy basic phos- phates. In the state of hunger it acquires the character of the urine of carnivora, as under these conditions the animal in a certain measure lives upon its own tissues. THE ORGANIC CONSTITUENTS OF THE URINE. 475 THE ORGANIC CONSTITUENTS OF THE URINE. UREA: CO(NH 2 ) 2 . Urea, the diamid of CO 2 or carbamid must be considered as the principal end-product of the oxidation of the nitrogen-containing consti- tuents of the body. It has the following extremely simple composi- tion: i atom of carbon dioxid -f- 2 atoms of ammonia i atom of water. It crystallizes in silky-glistening, four-sided prisms, with oblique ends, be- longing to the rhombic system (Fig. 146, i, 2), without water of crystallization ; when rapidly crystallized it forms delicate, white needles. It has no in- fluence upon litmus, is odorless, and of a feeble bitter, cooling taste like that of potassium ni- trate. It is readily soluble in water and in alcohol, but almost insoluble in ether. It is isomeric with ammonium cyanate, from which it develops on evapora- tion through atomic displace- ment. Numerous other modes of artificial preparation are known. Heated to a temperature above 120 it is decomposed, with the de- velopment of vapors of ammonia, and leaving a vitreous mass of biuret and hydrocyanic acid. In the pro- cess of ammoniacal putrefaction and as a result of treatment with strong mineral acids, of boiling with alka- line hydrates and of heating with water at a temperature of 240 C., it takes up two atoms of water and yields ammonium carbonate: CO(NH 2 ) 2 + 2 H 2 O = CO(ONH 42 ). Brought in contact with nitrous acid it is decomposed into water, carbon dioxid and nitrogen. The last two forms of decomposition have been employed for the quantitative estimation of urea. The amount of urea in normal urine is between 2.5 and 3. 2 per cent. Adults excrete daily about from 30 to 40 grams; women less; children relatively more. In accordance with the more active metabolism in the latter, the amount of urea furnished by the weight-unit of the child's body, as compared with that of the adult, is as 1.7 to i. If the body is in a condition of metabolic equilibrium almost as much nitrogen is eliminated in the form of urea as is introduced into the body with the food. The amount of urea increases with the amount of proteids in the food, FIG. 145. Graduated Buret. 476 UREA. as well as with the degree of disintegration of the nitrogen-containing tissues in the body. As the latter is increased by withholding oxygen and by hemorrhage, these also cause an increase in the amount of urea. The administration of large amounts of water by more thorough washing out of the tissues and also of salts, frequent micturition and exposure to compressed air likewise increase the amount of urea. In diabetics who partake of large amounts of food, the amount of urea occasionally exceeds 100 grams daily, while in the state of hunger it falls to 5.6 grams. In the state of inanition a maximum of elimination has been observed toward noon, and a minimum toward morning. Daily variations in the amount of urea pursue a course parallel with the amount of urine. Three or four hours after digestion begins the forma- tion of urea reaches its maximum, subsequently falling again and reaching its minimum during the night. The excretion of urea, and in the same proportion that of the total nitrogen, with the urine is materially aug- mented in consequence of increased muscular activity. This excretion FIG. 146. i, 2, Prisms of pure urea; 3, rhombic plates; 4, hexagonal tablets; 5, 6, irregular scales and plates of urea nitrate. is less on the first working day, as observed in dogs, than on the second and third, but it is still increased on the two resting days succeeding the work. Pathological. In the presence of acute febrile inflammatory processes and of fever in general, the excretion of urea increases to the height of the morbid process, in association with which it again declines. After the cessation of the process the excretion is often subnormal. At times the formation of urea may be in- creased in association with high fever, but the excretion may be checked and retention of urea takes place. In the further course of the disorder the excretion may be greatly increased. In chronic diseases the amount of urea varies with the state of the nutrition, the metabolism of the patient and in accordance with the height of the accompanying fever. Degenerative disorders of the liver, as, for instance, from phosphorus-poisoning, may be attended with diminished excre- tion of urea and increased excretion of ammonia. Substances that increase the proteid disintegration in the body, as, for instance, arsenic, antimony-combinations, and small amounts of phosphorus, increase the formation of urea; while those that conserve proteids, as, for instance, quinin, diminish the production. Increased formation of bile in the liver gives rise at the same time to increased formation of urea. UREA. Urea represents the end-product of the metabolism of proteids. Next in order there stand, as lower stages of oxidation, uric acid, guanin, xanthin, hypo- xanthin, alloxan and allantoin. Uric acid administered as urates appears in the urine as urea, being transformed by the liver, with increase in the secretion of bile. Muscle-extractives have the same effect, and in general increased formation of bile is attended with augmented formation of urea. After administration of leucin, glycin, aspartic acid or of ammonium-salts an increase in the excretion of urea takes place. The liver is the principal, but not the sole seat of the formation of urea. The correctness of the supposition of Schmiedeberg that the urea is derived from ammonium carbonate through loss of water was demon- strated by v. Schroder, who found urea in large amount in blood to which ammonium carbonate had been added, and made to pass through a recently removed liver. It is, therefore, to be concluded that am- monium-combinations derived from nitrogen-containing tissues as meta- bolic products pass over into the circulation, through which they are conveyed to the liver for the formation of urea. The organism is capable of converting considerable amounts of ammonia, as, for instance, in the form of lactate or acetate, into urea. The liver forms urea also from the ammonia in the blood of the portal vein. In the metabolism especially of proteids there is formed in many organs by oxidation car- bamic acid, CO 2 NH 3 , which likewise is transformed principally in the liver into urea, and also the amido-acids. If acids are taken into the body before the ammonium-combinations are transformed into urea, there result ammonium-salts, with a corresponding reduction in the amount of urea in the urine. Under pathological conditions the urea-forming activity of the liver may be diminished. After extirpation of the liver, the urine no longer contains urea, and likewise after exclusion of the hepatic circulation, but on the other hand large amounts of ammonium- salts. Eck, in the dog, diverted the blood of the portal vein directly into the inferior vena cava, by establishing an artificial communication between the two vessels, and then ligated the portal vein close to the liver. The dogs were seized with severe nervous attacks and convulsions. As, according to v. Schroder, ammonium- salts are transformed in the liver into urea, this transformation is thus almost wholly prevented, and the substances named now exert a toxic effect upon the nervous system. By injection of a 6.2 per cent, solution of sulphuric acid into the bile duct, in the dog, all of the liver-cells became necrotic, and the animal died in one or two days with signs of prostration, mental derangement, loss of sensibility, central narcosis and finally convulsions. From this it has been concluded that the liver serves the purpose of converting a toxic metabolic product, carbamic acid, into an innocuous one, urea. In birds the liver thus produces the largest amount of uric acid from the ammonium supplied. As birds readily tolerate ablation of the liver, Minkowski observed after this operation reduction in the amount of uric acid and in- crease in the amount of ammonium-salts in the urine. Urea is present in the following parts of the body: Blood (i : 10,000) ; lymph, chyle (2 : 1,000); liver, lymphatic glands, spleen, lungs, brain, eye, bile, saliva, amniotic fluid; by Schondorff it was found in the muscles and the erythrocytes and in almost all of the organs of the dog; besides, pathologically, in the sweat, as, for instance, in cases of cholera, as well as in the vomitus and in dropsical fluids of uremic patients. The preparation of urea can be accomplished directly from dogs' urine, after generous feeding with meat, the fluid being evaporated to a syrupy consistency, extracted with alcohol, the filtered extract again evaporated, the crystals thus separated freed of the adherent extractives by means of alcohol and then dis- solved in absolute alcohol. Filtration is practised again and evaporation is per- mitted to take place until crystallization occurs. A given volume of human urine 478 QUALITATIVE AND QUANTITATIVE ESTIMATION OF UREA. is evaporated to one-sixth of its original volume, is reduced to a temperature of o and an excess of strong, pure nitric acid is added. Urea nitrate contaminated with coloring-matter is precipitated. The precipitate is filtered, expressed, dis- solved in a little boiling-water, mixed with animal charcoal for the removal of the coloring-matter, and filtered hot. On cooling, decolorized crystals of urea nitrate separate from the filtrate. These are again dissolved in hot water, and barium carbonate is added so long as effervescence takes place. Barium nitrate and free urea are thus formed. Evaporation to dryness is now practised, fol- lowed by exhaustion with absolute alcohol, filtration and evaporation, after which the urea separates in crystals. Combinations of Urea. Urea is capable of entering into combination with acids, as nitric, oxalic or phosphoric, or with bases, or with salts, as sodium chlorid, mercuric nitrate. The most important combinations are: 1. Urea nitrate: CH 4 N 2 O.NO 3 H, whose mode of preparation from the urine has just been described. The preparation of urea nitrate is employed with advant- age for the microscopic demonstration of urea. If there are but a few drops of watery fluid in which the presence of urea is suspected and this must be so prepared that the urea present is in concentrated watery solution one drop of this fluid is placed upon a glass slide, a thread is laid through the middle of the drop and over both is placed a cover-slip. From the extremity of the thread a drop of concentrated nitric acid is permitted to find its way beneath the cover-slip. The characteristic crystals appear upon either side of the thread (Fig. 146, 3, 4, 5, 6). Urea nitrate is readily soluble in water, soluble with difficulty in water acidulated with nitric acid. Less commonly, when crystallization takes place slowly, it yields six-sided prisms. 2. Mercuric-nitrate urea is obtained in the form of a white, cheesy precipitate, when mercuric nitrate is introduced into a solution of urea. If, on the develop- ment of the precipitate, the nitric acid set free is neutralized by sodium carbonate, all of the urea eventually combines with the mercuric salt. When this point has been reached, all excess of mercuric nitrate gives rise, on addition of sodium carbonate, to the production of sodium nitrate and yellow basic mercuric carbo- nate. The titration-method of J. v. Liebig for urea is based upon this reaction. QUALITATIVE AND QUANTITATIVE ESTIMATION OF UREA. The qualitative estimation of urea aims (i) at the preparation of this substance directly as such. If its presence be suspected in an albuminous fluid mixed with blood or pus, the following course is pursued: Three or four times its volume of alcohol are added to the fluid, and filtration is practised after the lapse of several hours. The filtrate is evaporated over the water-bath, and the residue is dis- solved in a few drops of water. (2) This aqueous solution is employed for the microchemic preparation of urea nitrate, which has important diagnostic signifi- cance. (3) By means of a solution of sodium hypobromite, the urea in the fluid submitted to examination is decomposed into carbon dioxid, water, and nitrogen. The nitrogen rises in the mixture in the form of small bubbles. The Knop- Hiibner method of quantitative estimation is based upon this reaction. (4) A crystal of urea is cautiously fused in a dry test-tube, and yields an odor of am- monia. On cooling, it is dissolved in a small amount of water, and sodium hy- drate, together with one drop of dilute copper sulphate, is added, with the develop- ment of a red-color biuret-reaction. Quantitative estimation of urea in the urine, according to the method of Morner and Sjoqvist: To 2.5 cu. cm. of urine are added 2.5 cu. cm. of baryta-mixture (i volume of a cold saturated solution of barium hydrate and 2 volumes of cold saturated barium nitrate) and 75 cu. cm. of ether-alcohol (the alcohol must be 70 per cent.). The mixture is preserved for a day sealed. It is now filtered, and the filtrate, which contains of the nitrogenous substances only the urea, is evaporated at a temperature of 55 C. after the addition of 0.5 gram of magnesium oxid. After the addition of 10 cu. cm. of sulphuric acid it is further evaporated upon a boiling water-bath, until no further reduction in volume takes place. Then it is placed in a Kjeldahl boiling-flask, and the examination is continued according to the Kjeldahl method. The method of Kjeldahl is employed for the estimation of the total amount of nitrogen in the urine. It is based upon the fact that all of the nitrogen is transformed into ammonia, and this is estimated quantitatively. Five cu. cm. of urine of moderate concentration are measured by means of a pipet and intro- URIC ACID. 479 duced into a flask having a capacity of about 200 cu. cm., with 20 cu. cm. of pure English sulphuric acid (to one liter of which 200 grams of phosphoric anhydrid are added) , and one drop of metallic mercury ; and this is boiled over the sand- bath until the fluid, which at first was dark, is entirely decolorized. On cooling, the fluid is rinsed with about 200 cu. cm. of water into a flask having a capacity of half a liter, and 100 cu. cm. of sodium hy- drate (of a sp. gr. of 1.34), a few cu. cm. of an aqueous solution of potassium sulphid, and some powdered zinc are added. The flask is then quickly closed with a stopper and the ammonia set free is distilled into a receiver containing 50 cu. cm. of one- tenth normal sulphuric acid. The extremity of the tube from which the ammonia escapes must be immersed in the normal sulphuric acid. In order to determine whether all of the am- monia is present in the receiver, the stopper of the receiver is cautiously removed, a strip of litmus-paper is placed by means of a pair of forceps in front of the tube conveying the ammonia. . and note is made whether the escaping distillate causes the strip to turn blue. The amount of sulphuric acid in the receiver not saturated by ammonia is determined by titration with one-tenth normal sodium hydrate. According to Pfliiger and Bohland, the amount of nitrogen in the urine can be estimated approximately by the following simple method: To 10 cu. cm. of urine, Liebig's urea-titrating solution is added from a buret, and the mixture is tested upon a dark glass plate with sodium bicarbonate drop by drop, as in the estimation of urea. If the stirred stain remains yellow, the number of cubic centimeters of titration-fluid employed is mul- tiplied by 0.04 and in this way the percentage of nitrogen present is obtained. The total amount of nitrogen in the urine is to the nitrogen in the urea approximately as 5 to 4. FIG. 147. Gradu- ated Pi pet. URIC ACID C 5 H 4 N 4 3 . Next to urea, the greatest amount of nitrogen is eliminated as uric acid, namely, 0.5 gram in 24 hours (in the state of hunger, 0.24 gram ; after a generous meat- diet, 2. ii grams). The amount of uric acid is to that of urea on the average as i to 46, though with many varia- tions. In the mammalian body the uric acid is formed from the nuclein of the disintegrating leukocytes. With increase in the latter, there is increase in the amount of uric acid formed. Ingestion of nuclein as, for instance, after the eating of thymus gland increases the number of leukocytes in the blood and the excretion of uric acid. Xanthin-bases (guanin, xanthin, hypoxan- thin) occur in the intestines as products of the digestion of nucleins. If they be increased in amount, an increase in the amount of uric acid results. In birds, reptiles and insects, uric acid is the principal nitrogenous excrementi- tious product; while it appears in but small amount in the urine of herbivora. The products of the decomposition of leukocytes present in surviving splenic pulp (nuclein) yield, when treated with fresh blood at the temperature of the body, an abundance of uric acid, together with xanthin and hypoxanthin. Also the nuclein of the nuclei of many other tissues has also shown itself to be a source of uric acid. In addition to uric acid, xanthin-bodies are formed in the same way. When animals are fed with nucleinic acid and hypoxanthin, the elimination of uric acid is increased. Uric acid fed to mammals passes into the urine in part further oxidized into urea, together with an increase in the amount of oxalic acid. In hens there is increased elimination of uric acid after the administration of leucin, glycin, aspartic acid, hypoxanthin, or ammonium carbonate. The urea administered to hens is, however, eliminated chiefly reduced to uric acid. 48o URIC ACID. Uric acid is dibasic, tasteless, odorless, and colorless, soluble with great difficulty in water (in 15,000 parts of warm, or 18,000 parts of cold water, though in 2,000 parts of a 2 per cent, solution of urea), insoluble in alcohol or ether. It crystallizes in various forms (Fig. 148), the basic type of which is the rhombic plate (i). Enlargement of the op- posed larger angles causes the formation of the whetstone-shape fre- quently observed (2). If the longer sides of the latter are flattened, six-sided plates result. Large, golden-yellow crystalline resets (6, 8) often separate spontaneously from diabetic urine. Precipitated by addition of hydrochloric acid (25 cu. cm.) to urine (one liter) or of acetic acid, the crystals usually assume the form of a barrel (9) or a bundle of spears that are tinged brownish violet by adherent urea. Uric acid is readily soluble in alkaline carbonates, borates, phosphates, lactates, and acetates. Removing a portion of the base from these salts, there result, on the one hand, acid urates; and on the other hand, acid salts from the neutral FJG. 148. Different Forms of Uric Acid: i, rhombic plates; 2, whetstone-shape; 3, quadratic shape; 4, 5. elon- gated forms with two pointed extremities; 6, 8, arrangement of several crystals in the form of a roset; 7, crystals drawn out into the shape of a lance; 9, so-called barrel-shape obtained from human urine by means of hydrochloric acid, in part darkly discolored. salts. Among alkalies, lithium (citrate) is especially noteworthy as a solvent of uric acid. According to v. Noorden and Strauss, a favorable composition of the urine will be obtained if calcium carbonate or calcium-salts of the vegetable acids (from 2 to 10 grams) are administered. Phosphoric acid leaves the body with the cal- cium through the intestines. In consequence, the monosodium phosphate in the urine is diminished, as it gives up the phosphoric acid and thus disodium phos- phate results. The latter, however, is capable of dissolving uric acid, inasmuch as sodium urate and monosodium phosphate are formed. Uric acid is soluble in concentrated sulphuric acid, from which it is reprecipitated by water. Plumbic oxid converts it into urea, allantoin, oxalic acid and carbon dioxid; ozone pro- duces the same substances, together with alloxan. Reduced by hydrogen in a nascent state, xanthin and sarcin are produced. Horbaczewski has prepared uric acid synthetically by fusing one part of glycin and seven parts of urea. In the urine, the uric acid is dissolved principally in the form of acid sodium and potassium urate. These salts are present also in urinary URIC ACID. 481 sediments, urinary sand, and urinary calculi. Ammonium urate is con- tained in lateritious sediment in but small amount, being formed in large amount only as a result of ammoniacal decomposition of the urine (Fig. 154). Free uric acid occurs in normal urine only in the smallest amount . It is, however, not rarely precipitated subsequently on standing (Fig. 153). and it is present, further, also in urinary sand and calculi. De- ficiency of neutral phosphates in the urine favors the formation of uric- acid sediment. The urine of the new-born is rich in uric acid (uric-acid infarct of the kidneys) . The uric acid, together with its salts, is increased by marked muscular activity attended with perspiration, also in the presence of catarrhal and rheumatic fevers and such as are attended with derangement of respiratory activity; further, in cases of leukemia with increased leukocyte-destruction and splenic tumor, granular liver; and, finally, quite generally in connection with gastric and intestinal catarrh following excessive indulgence in alcohol, after generous ingestion of cheese and salt fish or salt meat, after administration of glycerin, and a diet containing nuclein. Hypoxanthin fed to birds is eliminated in part transformed into uric acid. The amount of uric acid is diminished after generous ingestion of fresh fruits (strawberries, cherries, grapes) or of quinic acid or alkaline salts of the vegetable acids contained in them; further, after hot baths; also after ingestion of proteids in large amount and after the administration of caffein, potassium iodid, sodium chlorid, sodium carbonate, lithium carbonate, sodium sulphate, inhalations of oxygen, gentle muscular exercise, though not after copious ingestion of water. In cases of gout in which uric acid is deposited in the gouty nodules, its elimination is slight. In the presence of chronic splenic tumor, anemia, and chlorosis, it is diminished, particularly if no respiratory disorder is at the same time present; and likewise in cases of epilepsy in advance of an attack. The Urates. With various bases uric acid forms principally acid urates, which are soluble with difficulty in cold water and readily in hot water. Neutral urates are transformed by carbon dioxid into acid salts. Hydrochloric and acetic acids dissolve the combinations and the uric acid separates in the form of crystals. Acid sodium urate, sodium biurate, has a neutral reaction, and ap- pears as a uratic sediment (lateritious sediment) generally of a brick- red color from uroerythrin (according to Hoppe-Seyler from urobilin) less commonly it is between light gray and whitish in color in the presence of catarrhal digestive disorders and of rheumatic and febrile affections. Microscopically it appears as amorphous granules (Fig. 153, b). The sediment is dissolved by heating the urine. Not rarely the sediment contains also the potassium-salt, which is entirely similar Acid ammonium urate is soluble with difficulty in water, is always present, as a sediment, in ammoniacal urine, appears in reflected light in the form of yellowish spheres of thorn-apple or morning-star shape- in transmitted light of a darker color and is frequently accompanied by triple phosphates (Fig. 154, a). Acid sodium urate and acid ammonium urate are recognized by the separation of free uric-acid crystals in microscopic preparations, after addition of a drop of hydrochloric acid. Acid calcium urate, occasionally present in urinary calculi, is a white amorphous powder soluble with difficulty in water. Fused upon a platinum plate, it leaves a residue of calcium carbonate. Rarely magnesium urate occurs in urinary calculi. 3 1 482 QUALITATIVE AND QUANTITATIVE ESTIMATION OF URIC ACID. QUALITATIVE AND QUANTITATIVE ESTIMATION OF URIC ACID. Qualitative Estimation. i. The microscopic demonstration of uric acid and the urates is based upon the characteristics that have been described. Uric acid is precipitated from urine by addition of acetic or hydrochloric acid. 2. The murexid test. Uric acid or urates are heated in a shallow dish with nitric acid at a low temperature. Decomposition takes place, with the develop- ment of a. yellow color. Nitrogen and carbon dioxid escape, while urea and alloxan (C 4 H 2 N 2 O 4 ) remain behind. Evaporation is now cautiously carried further, and the resulting yellowish-red stain is permitted to cool. The addition of a drop of dilute ammonia produces a purple-red color (murexid = ammonium purpurate: alloxantinamid) . This red color becomes blue on further addition of potassium hydrate. If, at the outset, potassium or sodium hydrate is added to the stain, instead of ammonia, a violet color results. 3. If upon a strip of filter-paper saturated with a solution of silver nitrate is dropped uric acid or urate dissolved in an alkaline carbonate, a black stain at once appears through reduction of the silver. Quantitative Estimation. i. The method of Hopkins, by means of which the uric acid is precipitated as ammonium urate. If 100 cu. cm. of urine are thor- oughly saturated with ammonium chlorid (about 30 grams are necessary), all of the uric acid is precipitated as ammonium urate, particularly if some ammonia is added besides. After the lapse of two hours the precipitate is collected upon a filter, where it is washed several times with a saturated solution of ammonium chlorid. The precipitate is now rinsed from the filter with boiling water, and exposed to the action of hydrochloric acid with heat. The uric acid that sepa- rates is collected upon a dry filter, and is again dried and weighed. 2. The method of Salkowski, modified by E. Ludwig, is based upon the pre- cipitation of the uric acid by silver nitrate and its subsequent separation and weighing. The following solutions are necessary : A . Twenty-six grams of silver nitrate dissolved in water, and admixed with ammonia, until complete solution takes place; then addition of water to make i liter. B. Magnesia-mixture: 100 grams of crystallized magnesium chlorid dissolved in water; ammonia added until a strong odor is developed; then ammonium chlorid to the solution; and, finally, addition of water to make i liter. C. Ten grams of pure sodium hydrate dissolved in i liter of water. One-half of this is completely saturated with hydro- gen sulphid, and then both halves are mixed. Mode of Procedure. One hundred cubic centimeters of filtered non-albumin- ous urine (if necessary freed of albumin) are placed in a beaker. In another glass, 10 cu. cm. of the solution A are mixed with 10 cu. cm. of the solution B, and ammonia is added, if necessary also ammonium chlorid to the point of complete saturation. This solution is poured with stirring into the urine, and the mixture is permitted to stand for one hour. The precipitate is then collected upon a filter, is washed with water containing ammonia, and is brought, by means of a pipette and a glass rod, without injury to the filter, back again into the beaker. Now 10 cu. cm. of the solution C, diluted with 10 cu. cm. of water, are heated to the boiling-point, and this solution is passed through the used filter into the beaker which contains the silver-precipitate; the filter is then washed with hot water, and the beaker is heated for some time over the water-bath with stirring. On cooling, the solution is filtered into a dish; the filter is washed with hot water; the filtrate is acidulated with hydrochloric acid; and the product is evaporated to about 15 cu. cm., when 15 drops of hydrochloric acid are added, and the solution is permitted to stand for twenty-four hours. The uric acid separated out is col- lected upon a previously weighed filter, washed with water, alcohol, ether, and hydrogen sulphid; dried at a temperature of 100 and weighed. For every 10 cu. cm. of the watery filtrate, 0.00048 gram of uric acid are to be added. KREATININ, XANTHIN-BASES, OXALURIC, OXALIC, AND HIPPURIC ACIDS. Kreatinin (C 4 H 9 N 3 O 2 ) is derived in part from the kreatin present in the muscles by loss of water, and in part from the meat in the food. Its amount daily is from 0.6 to 1.3 grams. The amount of kreatinin is diminished in cases of progressive muscular atrophy, of tetanus, and of marantic, anemic, or paralytic conditions of the musculature. KREATININ, XANTHIN BASES, OXALURIC AND OXALIC ACIDS. 483 It is increased particularly by greatly augmented muscular activity, after the ingestion of food rich in nitrogen. It is wanting in the urine of infants. Kreatinin yields an alkaline reaction, is readily soluble in water and in hot alcohol, and it forms colorless, oblique rhombic columns. It combines with acids, but also with salts. Kreatinin-zinc chlorid is prepared for the detection of krea- tinin. Demonstration. A few drops of a slightly brown, watery solution of sodium nitroprussid and then dilute sodium hydrate added to 5 cu. cm. of urine cause a Burgundy-red color that soon disappears. Addition of acetic acid changes the color to yellow. Acetone yields a similar reaction, though in the case of this substance the red color becomes still darker, almost purple, after addition of acetic acid. Acetone can first be driven off from the urine by boiling, and then the reaction of kreatinin is certain. Xanthin-bases : Alloxuric Bases. Under the names xanthin-bases or nuclein- bases, or alloxuric bases, are comprised a group of bodies, including xanthin, hypoxanthin, adenin, guanin, carnin, which are related genetically to uric acid, and, together with it, are also designated alloxuric bodies. The mother-substance of all alloxuric bodies, including uric acid, is purin (C 5 N 4 H 4 ), from which are derived: hypoxanthin, as oxypurin; xanthin, as dioxypurin; uric acid, as trioxy- purin; adenin, as 6-aminopurin; guanin, as 2-amino-6-oxypurin. By the en- trance of one methyl-group into the xanthin-molecule, there result the isomers, i-methylxanthin, 3-methylxanthin, y-methylxanthin (heteroxanthin) . If two methyl-groups enter, there are formed theobromin, paraxanthin, and theophyllin. If 3 methyl-groups enter, caffein is formed. Salomon and Kruger found in the urine hypoxanthin, xanthin, adenin, hetero- xanthin, paraxanthin, i-methylxanthin, y-methylguanin; and of the foregoing, respectively, in 10,000 liters of urine, 8.5 grams, 10.1 grams, 3.5 grams, 22.3 grams, 15.3 grams, 31.3 grams, 3.4 grams. Alloxuric bases are prepared from the urine as combinations with silver or copper, and these are decomposed by hydrogen sulphid. The crude bases, treated with dilute hydrochloric acid, exhibit varying solubility. The vegetable alkaloids of coffee, tea, and cocoa are the antecedents of heteroxanthin. Paraxanthin is derived from caffein. Studies of the alloxuric bodies, therefore, are of value only after protracted abstinence from the beverages named. Xanthin, C 5 H 4 N 4 O 2 , is present in small amounts only; according to E. Sal- kowski, it may, however, under some circumstances, be as much as one-eighth of the weight of uric acid. It is an amorphous, yellowish-white powder, quite readily soluble in boiling water. It is said to be present in the urine in somewhat greater amount after courses of treatment with sulphur, in leukemic patients and in conjunction with nephritis in children. Rarely it forms urinary calculi. It represents an intermediate link between sarcin and uric acid. Guanin and hypo- xanthin can be converted into xanthin. In contact with water and ferments, xanthin is transformed into uric acid. Evaporated with nitric acid, it leaves a yellow stain that becomes yellowish red with potassium and violet red when further heated. Hypoxanthin, sarcin, C 5 H 4 N 4 O, can be prepared in the form of needles or exfoliating scales from meat, milk, bone-marrow, liver, blood from the cadaver. It is present in normal urine in smaller amount. Hypoxanthin exhibits great resemblance to xanthin, into which it can be transformed by oxidation. Hydrogen in the nascent state conversely reduces uric acid to xanthin and hypoxanthin. Evaporated with nitric acid, it yields a light-yellow stain, which becomes more intense on addition of sodium hydrate, but not reddish yellow. It is more readily soluble in water than xanthin, and a means of differentiating the two is thus af- forded. Guanin is wholly insoluble in water. Paraxanthin has proved toxic in moderate amount to dogs. Rachford found it in the urine in considerable amount in cases of severe migraine with convulsive conditions. Oxaluric acid, C 3 H 4 N 2 O 4 , occurs in the urine in but small amount as an ammo- nium-salt, is but slightly soluble in water and appears as a loose white powder. Ammonium oxalurate can be prepared from uric acid. Perhaps there is a physio- logical connection between uric acid and oxaluric acid. Oxalic acid, C 2 H 2 O 4 , occurs, though not constantly, as calcium oxalate, to an amount varying from 10 to 25 mg. daily. It is recognizable from its envelop- shaped clear octahedra (Fig. 153, J), which are insoluble in acetic acid; biscuit- shaped or hour- glass shaped crystals (Fig. 159, c) are less common. The genetic relation between oxalic acid and uric acid appears demonstrated by the fact that OXALIC ACID, HIPPURIC ACID. dogs after being fed with uric acid excrete much calcium oxalate. It should, how- ever, be pointed out that the oxalic acid may also result as an oxidation-product from derivatives of the fatty-acid series. Oxalic acid is formed from oxaluric acid by the taking up of water, together with the appearance of urea. Oxalic acid is wanting on a pure milk-diet. Almost all vegetable articles of food contain it. The ingestion of substances that contain a considerable amount of calcium oxalate, such as sorrel and tea, increases the excretion. Citric acid, treated with ozone, yields carbon dioxid and oxalic acid. The presence of calcium oxalate after the use of lemons is thus explained. Increased elimination of oxalic acid in the urine is designated oxaluria, and is considered in part a sign of retarded metabolism, as, for instance, from deficiency of oxygen, in the dog; and in part as dependent upon hyperacid- ity of the gastric juice. It may become dangerous in conse- quence of the formation of cal- culi. In conjunction with oxa- luria, the uric acid has often been found increased. The amount of oxalic acid is in- creased in the urine of jaun- diced persons. According to Neubauer, dissolved calcium oxalate, held in solution by acid sodium phosphate, also occurs in the urine. The elim- ination of this substance takes place in crystalline form the more completely, the more nearly the urine approaches a neutral reaction. Hippuric acid, C 9 H 9 NO 3 , benzoylamidoacetic acid, oc- curs in the urine of herbivora, and as the principal represen- tative of the nitrogenous prod- ucts of metabolism; and in human urine only in small amount from 0.3 to 3.8 grams in a day. It is an odorless, monobasic acid, with a bitter taste, crystallizing in color- less four-sided prisms; and it is readily soluble in alcohol, but only in 600 parts of water. It is a conjugate acid and results in the body from benzoic acid (or from the cuticular substance of plants, which is closely related to it) , or from oil of bitter almonds, cinnamic acid, quinic acid (in hay), which are readily transformed by reduction (quinic acid) or by oxidation (cinnamic acid) into benzoic acid, with which glycin combines with the giving up of water. C 7 H 6 O 2 + C 2 H 5 NO 2 = C 9 H 9 NO 3 + H 2 O Benzoic Acid Glycin Hippuric Acid Water. The formation of hippuric acid is, accordingly, dependent principally upon the food. It is, therefore, wanting in the urine of nursing calves, as well as after the ingestion of such vegetables as possess no cuticula; as, for instance, earthy bulbs and peeled vegetables. Similar syntheses of glycin occur in the organism also after ingestion of many other substances, as, for instance, after administration of substituted benzoic acids or of aromatic acids. As the albuminates also are capable of yielding benzoic acid and oil of bitter almonds through oxidizing agents, the hippuric acid may be formed in the body from disintegrating albuminates. This explains the fact that it is found also in the urine of fasting persons. In the dog, the conjugation of hippuric acid takes place in the kidneys; in frogs, also outside these organs. Kuhne and Hallwachs refer the formation to the liver, Jaarsfeld and Stokvis to the kidney, the liver and the intestines. The observation of Salomon that hippuric acid was present in the blood and in the liver of nephrectomized rabbits after injection of benzoic acid into the blood indicates that the formation does not take place exclusively in the kidneys. Fur- ther, the hippuric acid formed in human beings may, under pathological condi- tions, particularly when the reaction is alkaline and albuminuria is present, be again decomposed in the urine, in consequence of a fermentative process. Whether FIG. 149. Kreatinin-zinc Chlorid: a, spherical aggregations with radiate striation; b, groups after crystallization out of water; c, less common form from alcoholic extract. ALLANTOIN, COLORING-MATTERS OF THE URINE. 485 the hippuric acid formed is already decomposed in the blood and the tissues of man is doubtful. In the kidneys of swine and of the dog, fermentative decom- position of hippuric acid takes place. After ingestion of pears, prunes, cranberries, unpeeled apples, the amount of hippuric acid increases greatly. It is increased also in the presence of jaundice, diseases of the liver, and diabetes. If it be contained in the urine in large amounts, it appears in the sediment, from which it can be isolated by boiling with alcohol. Boiled in strong acids or alkalies, or in combination with putrid substances or the micrococcus ureae, it is decomposed again into benzoic acid and glycin, with the taking up of water. The urine of the dog contains, in addition to uric acid, kynuric acid, C 10 H 14 N 3 O 6 + H 2 O, and uroprotic acid, C 66 H 116 N 2rt SO 54 + H 2 O. Allantoin, C 4 H 6 N 4 O 3 , a constituent of the amniotic fluid of the cow, in lesser degree of that of human beings, is normally present in the urine in traces, especially after the eating of meat; in larger amount in the first week of life and in pregnant women, as well as after administration of thymus gland and pancreas. The amount increases after the ingestion of considerable amounts of tannic acid; in the dog, from the oxidation of uric acid fed. Allantoin forms glistening, pris- matic crystals. It crystallizes in transparent prisms from the urine of nursing calves on evaporation to a sirupy consistence, and standing at rest for a day. It is decomposed by ferments into urea, ammonium oxa- late and carbonate, and another sub- stance whose identity has not yet been established. It is readily sol- uble in water, with difficulty in alco- hol, and not at all in ether. For its preparation, the urine is precipitated by means of basic lead acetate, the lead being removed from the nitrate by means of hydrogen sulphid. The fluid is then evaporated to a sirupy consist- ence, and the crystals separate in the course of days. These are washed with water and recrystallized out of hot water. Oxyproteic acid is an oxidation-product of albumin containing nitrogen and sulphur. It can be prepared as a baryta-combination, is soluble in water but not in alcohol, and is precipitable by mercuric nitrate and sulphate. On a mixed diet, it constitutes from 2 to 3 per cent, of the total nitrogen, thus some- what more than the uric acid. It is greatly increased in cases of phosphorus-poison- ing, and perhaps also in conjunction with other forms of proteid decomposition. FIG. 150. Hippuric Acid. COLORING-MATTERS OF THE URINE. Urobilin is present in considerable amount in highly colored febrile urine, often also in normal urine, particularly after the ingestion of readily digestible food and after the termination of gastric digestion; in small amount in the state of hunger and during the process of gastric digestion. It is a derivative of hematin, or of the biliary coloring- matter resulting therefrom. It closely resembles the hydrobilirubin of Maly, from which, however, it differs in the greater amount of nitro- gen it contains. It gives the urine a red or reddish-yellow color, which becomes yellow after admixture with ammonia. Urobilin can be extracted from some urine by agitation after addition of an equal volume of ether or chloroform. The urobilin passes over into the latter, 486 COLORING-MATTERS OF THE URINE. and if this be permitted to evaporate, it remains as a residue. It is soluble in ammonia-water or in dilute soda-solution. If urobilin be dissolved in dilute sodium hydrate and a small amount of calomel be added, the yellow solution becomes rose-red (urorosein). If a chloroform-extract be prepared by agitation of urine containing urobilin, and if iodin be added, and be combined by agitation with dilute potassium-solution, the solution acquires a color varying from yellow to brownish yellow, with a beautiful fluorescence in green. This reaction can also be applied directly to any urine containing urobilin. At times the urobilin, on standing, undergoes a modification, and then the usual reactions fail. If sodium or potassium carbonate be added to the urine, the characteristic ab- sorption-band at F approaches b and becomes much darker and more sharply de- fined. According to Hoppe-Seyler and Saillet, urobilin develops in the urine only after evacuation by the taking up of oxygen on the part of another body forming urobilin (Jaffe's chromogen). If acetic ether be added to recently discharged urine acidulated with acetic acid and agitation be practised, the chromogen passes over into the ether. If the acetic ether be agitated in sunlight with water, uro- bilin is formed; and this can be again shaken out by means of chloroform. If zinc chlorid be added to urine containing urobilin and rendered alkaline by addition of ammonia, the urine exhibits marked fluorescence, with a distinct green luster, particularly in reflected rays of sunlight. The isolated urobilin is fluorescent also without addition of zinc chlorid. Phosphotungstic acid precipitates all urobilin as a rose-colored deposit, which is soluble in water, and, after addition of hydro- Red. Orange. Yellow. _-~~ B 40 Green. 70 SO 9O 10O 110 FIG. 151. Spectrum of Urobilin in Acid Urine. Red. Orange. Yellow. Green. Cyan-blue. ' -^ 110 A a JB C 40 50 D 60 El) F 70 80 00 100 FIG. 152. Spectrum of Urobilin in Alkaline Urine. chloric acid, also in chloroform. By the employment of reducing agents (sodium- amalgam) a colorless reduction-product is formed from urobilin; but this, on standing in the air, is retransformed into urobilin, with the taking up of oxygen. The colorless body is identical with the chromogen that Jaffe found in urine. In many cases of jaundice, in which, at times, Gmelin's test for biliary pigment fails to develop, urobilin is present, particularly when incomplete biliary stasis exists. This urobilin-icterus occurs especially after the absorption of considerable extravasations of blood. According to Cazeneuve, the urobilin is increased in all diseases that are attended with increased destruction of red blood-corpuscles. Urochrome is considered by Thudichum as the peculiar yellow coloring-matter of the urine. It can be isolated in yellow crusts that are soluble in water, as well as in dilute acids and alkalies. The watery solution oxidizes in the air, with the development of a red color through the formation of uroerythrin. Treated with acids, further decomposition-products appear; among them, uromelanin. The uroerythrin often gives the urates a red color, the urochrome a yellow color. The latter, however, is by many not considered a well-characterized chemical body. Human urine saturated with ammonium sulphate yields, on agitation with 90 per cent, phenol, all of its coloring-matter to the latter. If this solution of phenol be mixed with ether and water, the water is stained yellow (urochrome), the phenol-ether mixture red (urobilin and hematoporphyrin) . INDICAN. 487 In the presence of melanotic neoplasms, black urine has from time to time been observed, due to melanin or a pigment containing iron. A brown pigment containing iron is carried down by the uric acid precipitated on addition of hydrochloric acid. By repeated addition of sodium urate to urine and precipitation of the uric acid by hydrochloric acid, this pigment can be obtained in considerable amount. SUBSTANCES FORMING INDIGO, PHENOL, KRESOL, PYROCATE- CHIN, AND SKATOL. OTHER SUBSTANCES. Indican, or the indigo-forming substance, is derived from indol, C 8 H 7 N, the mother-substance of indigo, which is formed in the intestine as a result of the pancreatic digestion of proteids, and as a putrefactive product. The indol, conjugated with the sulphuric-acid residue, SO 3 H, and combined with potassium, represents the indican, or indigogen of the urine (C 8 H 6 NSO 4 K, potassium indoxylsulphate). It forms white glistening tables and plates, readily soluble in water, slightly in alcohol. By oxidation it forms indigo-blue : 2 indican -f- O 2 = C 16 H 10 N 2 O 2 (indigo-blue) -j- sHKSO 4 (acid potassium sulphate). Jaffe found between 4.5 and 19.5 mg. of indigo in 1500 cu. cm. of normal human urine. Indigo is more abundant in the urine of inhabitants of the tropics, less abundant on a milk-diet, and it is wanting in the new-born. The urine of horses contains 23 times as much as human urine. Subcutaneous injections of indol increase the amount of indican in the urine. E. Ludwig obtained indican by heating hematin or bilirubin with potassium hydrate and powdered tin. It has been found also in the sweat. Demonstration. One-half of a test-tubeful of urine is mixed with an equal amount of hydrochloric acid, and 2 drops of a freshly prepared solution of chlorin- ated lime are added. The mixture becomes at first clear, then grayish blue. Now a few drops of chloroform are added, and the mixture is persistently agitated, the pigment being dissolved by the chloroform. If the mixture is permitted to stand, the blue chloroform-layer is deposited at the bottom. For quantitative estimation, the indican is transformed into indigo and further into sulphoindigotic acid, and this is titrated with a solution of potassium permanganate. Certain bacteria may produce indigo-blue in the evacuated urine, but also in the urinary passages; therefore, a lustrous bluish-red coating of microscopic rhombic crys- tals of indigo-blue upon the surface of putrid urine, or a precipitate thereof, is occasionally observed (Heller's uroglaucin) . Pathological. Indican is increased in the urine when the formation of indol is increased in the intestines in consequence of active putrefactive fermentation; as, for instance, in cases of typhoid fever, lead-colic, trichinosis, gastro-intestinal catarrh, hemorrhage from the stomach or bowel, diseases of the small intestine, cholera nostras, carcinoma of the liver and the stomach, strangulated hernia, peritonitis. As indican is developed as a result of the decomposition of pus, an increased amount in the urine may indicate the presence of suppuration, when the intestinal conditions are normal. Urine boiled with hydrochloric acid yields to the ethereal extract, together with indigo-blue, a garnet-red pigment, crystallizing in rhombic plates, namely indigo- red, urorubin, urorosein, which is developed by oxidation from an unknown chromogen. Its amount depends upon the same conditions as does that of indican. The urine thus extracted yields a brownish-black pigment to amylic alcohol, namely, uromelanin. All urinary pigments that are produced through the activity of acids are contaminated by dark-colored, nitrogenous humin-sub- stances, which are formed, in part, from the carbohydrates of the urine. Reaction for* Indigo-red. One- quarter of a test-tubeful of urine is boiled con- tinuously, with addition of nitric acid, drop by drop, until a red color is produced; it is then cooled and rendered alkaline with ammonia. If now it be gently agitated with 2 cu. cm. of ether, indigo-red dissolved in the ether passes over. The red reaction takes place in the presence of insufficiency of the intestine and its glands, in conjunction with severe diarrhea and most profound nutritive disorders. 488 PHENOL, KRESOL, PYROCATECHIN, AND SKATOL. Phenol, C 6 H 6 O, carbolic acid, occurs, according to Baumann, like- wise united with sulphuric acid, as phenol-sulphuric acid, C 6 H 5 OSO 3 H, which is found in the urine in combination with potassium. It is present in large amount in horses' urine. Phenol results from the decomposition of albuminates through pancreatic di- gestion, and especially through putrefactive processes. The mother-substance is tyrosin. - The formation of phenol-sulphuric acid is, therefore, entirely analogous to the formation of indican. Phenol, as well as kresol, is increased in the urine in the presence of infectious and suppurative diseases, as well as of diabetes, If phenol is employed internally or externally, the amount of phenol-sulphuric acid in the urine increases greatly. Therefore, sulphuric acid must unite with it. For this reason, alkaline sulphate is decomposed in the body, so that it may be entirely wanting in the urine. Living muscular structure or liver, digested for seven hours in a current of air with blood, with addition of phenol and sodium sulphate, forms phenol-sulphuric acid. Likewise, under these circumstances, pyrocatechin forms ether-sulphuric acid. The dark discoloration of the urine often observed in human beings after the internal or external employment of phenol depends upon oxidation of the phenol into hydroquinone (orthodioxybenzol, C 6 H 6 O 2 ), which appears in the urine in large part as ether-sulphuric acid. Parakresol (hydroxyltoluol, C 7 H 8 O) is present in larger amount than phenol, together with the isomers, orthokresol and metakresol, the latter in traces; also these, combined with sulphuric acid as kresol- sulphuric acids. For the demonstration of phenol, and also of kresol, 150 cu. cm. of urine are distilled with dilute sulphuric acid. The distillate yields, with bromin-water, a precipitate of tribrom-phenol, which soon crystallizes; as well as a red color with Millon's reagent. The hydroxylbenzols pyrocatechin and hydroquinone are given off after protracted heating of urine to which hydrochloric acid is added. Resorcin, which is isomeric with hydroquinone, leaves the body in the urine as ether-sulphuric acid when ingested. Toluol and naphthalin react in a similar manner. When benzol is administered, it is first oxidized into phenol. Pyrocatechin, C 6 H 6 O 2 , metadihydroxylbenzol, is formed, together with hydroquinone, from phenol; and it is likewise isomeric with hy- droquinone. In an analogous manner to indol and phenol, it is united with sulphuric acid. Infinitesimal amounts occur normally. It has been observed in larger amount by Ebstein and Miiller in the urine of a dyspeptic child. It can be recognized by the dark discoloration of the urine that results from putrefaction. Possibly pyrocatechin is formed in the body from decomposed carbohydrates, from which Hoppe-Seyler observed it to develop by heating with water under high pressure, as well as by treatment with alkalies. Skatol, which appears in crystalline form in the presence of in- testinal putrefaction, likewise appears in the urine as an ethereal sul- phate. Brieger found potassium skatoxyl-sulphate after feeding dogs with skatol. Demonstration. -The skatol-combination can be recognized by addition of dilute nitric acid, in consequence of which a violet color results; or of fuming nitric acid, in consequence of which red flakes are precipitated. Its amount varies with the same causes as does that of indican. Also hydroparacumaric acid and paraoxyphenylacetic acid, which belong to the aromatic oxyacids, are encountered in the urine in increased amount, together with a large amount of indican, in the presence of urticaria, acne, and senile pruri- tus, as signs of increased intestinal putrefaction. The first is a putrefactive product of meat, while the second has been obtained by E. and G. Salkowski from putrid albumin. Demonstration. If the urine, to which a mineral acid has been added, is SKATOL, OTHER ORGANIC CONSTITUENTS. 489 agitated with ether, the latter then evaporated, and the residue dissolved in water, it will yield a red color with Millon's reagent. This is the reaction of the aromatic oxyacids. Baumann has named the following list of substances that result from tyrosin by decomposition and oxidation, of which most members develop both as a result of the putrefaction of proteids in the intestine, and pass thence into the urine. Tyrosin, C ft H u NO 3 -fH 2 = C 9 H 10 O 3 (hydroparacumaric acid) +NH 3 . C 9 H 10 O 3 = C 8 H 10 O (parethylphenol, not yet demonstrated) +CO . C 8 H in O+O 3 = C 8 H 8 O 3 (paraoxyphenylacetic acid) +H 2 O. C 8 H 8 3 = C 7 'H 8 (parakresol)+CO 2 . C 7 H 8 O+O 3 = C 7 H 6 O 3 (paraoxybenzoic acid, not yet demonstrated) +H 2 O. C 7 H 6 O 3 = C 6 H 6 O (phenol) +CO 2 . Potassium sulphocyanate or sodium sulphocyanate is present in the urine in the proportion of from 0.02 to 0.08 gram to the liter, in larger amount in the urine of smokers. It is derived from the saliva and can be recognized by the ferric-chlorid test after acidulation with hydro- chloric acid. Succinic acid, C 4 H 6 P 4 , occurs particularly after the ingestion of meat and fat, and in infinitesimal amounts after the taking of vegetable food. It occurs in considerable amount as a product of the decom- position of asparagin, after the eating of asparagus. Also, as a product of alcoholic fermentation, it finds its way into the urine through in- gestion of spirit; or, administered internally, it passes undecomposed into the urine. Lactic acid, C 3 H 6 O 3 , is a constant constituent of the urine. Fermen- tation lactic acid has been found principally in cases of diabetes, sarco- lactic acid in cases of phosphorus-poisoning and of trichinosis. Traces of volatile fatty acids are inconstant. They occur par- ticularly in connection with destructive diseases of the liver. Ferments. Diastatic, peptic, and rennet-like ferments have been found by Griitzner principally in urine of high specific gravity. Fat-splitting ferment is not present normally. Trypsin is much attenuated. Traces of grape-sugar occur up to between o.oi and 0.05 per cent. After the ingestion of milk-sugar, cane-sugar, or grape-sugar (50 grams and more), these varieties of sugar appear unchanged in the urine in small amounts. Baisch found some isomaltose. Reducing substances (yielding Trommer's reaction) are always present in the urine. Normal human urine effects reduction almost like a 0.3 or 0.4 per cent. solution of grape-sugar, in larger measure in the presence of fever. Almost five- sixths of these substances are probably combinations of glycuronic acid, while one-sixth "consists of uric acid and kreatinin. There is present a dextrin-like carbohydrate and one soluble in alcohol, as well as some animal gum. Bechamp's nephrozymose consists principally of gum. This substance is prepared by pre- cipitating the urine with thrice its amount of 90 per cent, alcohol. It is not a simple body, and it transforms starch into sugar at a temperature of between 60 and 70 C. Acetone, C 3 H 6 O, appears after an exclusive diet of meat and fat, according to v. Noorden only on digestion of the flesh of the body. As soon as carbohydrates are taken, it is no longer observed. Also the digestion of the muscle and fat of the body occasions its appearance. Vicarelli found it in pregnant women with dead fetuses. Demonstration. One-half liter of urine is acidulated with hydrochloric acid and is distilled. On addition of tincture of iodin and ammonia, iodoform appears in the distillate as a cloudiness and is recognizable by its peculiar odor. Optically inactive urine that becomes discolored brown or black on exposure to the air after addition of alkali, with the taking up of oxygen and a powerful reducing activity, contains alkapton, homogentisic acid, which occurs but rarely, 4QO THE INORGANIC CONSTITUENTS OF THE URINE. and is produced from tyrosin (by the action of microorganisms?) within the body and then passes over into the urine. THE INORGANIC CONSTITUENTS OF THE URINE. The inorganic constituents of the urine either are taken into the body as such with the food and pass unchanged into the urine, or they are formed independently, inasmuch as the sulphur and the phosphorus of the food are consumed and unite with bases to form salts. From 9 to 25 grams of salts are eliminated daily. During sleep, the chlorin, potassium, and sodium in the urine are greatly reduced, sulphuric acid and the solid constituents of the urine generally are some- what reduced, while the acidity is considerably increased. Sodium Morid, table-salt, 12 grams (from 10 to 13 grams) daily, is increased after meals as the result of movement, of the copious drink- ing of water, of increase in the amount of urine generally, of generous administration of sodium chlorid, but also of potassium-salts. It is diminished principally under the reverse conditions. Under abnormal conditions the elimination of sodium chlorid is diminished in large measure in association with pneumonia and other affections attended with inflammatory exudation; further, in conjunction with most febrile disorders, except malaria, as well as with persistent diarrhea and sweating; constantly also when the urine contains albumin and when dropsy is present. Destruction of red blood-corpuscles increases the chlorids in the urine, while, on the contrary, the amount of chlorin in the urine (as well as in the gastric juice) is diminished in the presence of anemia, although the blood contains more chlorin than normal. Qualitative Estimation. Urine is acidulated in a test-tube with nitric acid, and a solution of silver nitrate is added, with the result that a white, cheesy deposit of silver chlorid takes place. The albumin must first be removed from albuminous urine by boiling. On microscopic examination, attention should be given in the evaporated preparation to the terrace-like arrangement of the cubes of sodium chlorid; and, at the same time, also to the rhombic prisms of sodium-chlorid urea. Quantitative Estimation, according to the method of Habel and Fernholz: 15 cu. cm. of the mixture of urine and baryta are acidulated, after neutralization, with 10 drops of dilute nitric acid having a specific gravity of 1 1 19, and a solution of silver nitrate, of which i cu. cm. fixes 10 mg. of sodium chlorid or 6.065 of chlorin, is added so long as a precipitate of silver chlorid is observed to take place. Then a small portion is filtered into a test-tube, and a test is made to determine whether turbidity results from addition of one or two drops of the silver-solution. If this be marked, the whole amount is poured back into the beaker, p.i cu. cm. of the silver-solution is added, and the test is repeated until the turbidity produced by two drops of the silver-solution is no longer particularly distinct. Now an equal amount is filtered into a second test-tube, and two drops of a one per cent, solution of sodium chlorid are added. If the turbidity is equally marked with that produced by two drops of the silver-solution, the correct point has been reached. Next, exactly so many cubic centimeters of the silver-solution are added to a new specimen acidulated with 10 drops of the nitric acid; and the intensity of the turbidity in the filtrate induced by two drops of silver-solution is compared with that induced by two drops of the one per cent, solution of sodium chlorid. If the turbidity caused by the sodium chlorid is the greater, 0.05 cu. cm. less of the silver-solution is added, and the turbidity of the filtrates is compared. Then so much more or less of the silver-solution is aclded as represents the differ- ence between the two points last found; and this is continued until an equal amount of silver nitrate and sodium chlorid produce equal turbidity in the filtrate. Titration of the chlorids according to the Freund-Topfer modification of Mohr's method: Ten cubic centimeters of urine are diluted to 25 cu. cm., and 2.5 cu. cm. of a mixture of 3 parts of acetic acid, 10 parts of sodium acetate, and 100 parts of water are added. Next, a few drops of a 10 per cent, solution of potas- sium bichromate are added, and titration is practised with the silver-solution (14.63 grams in 500 cu. cm. of water), until the well-stirred yellow fluid retains THE INORGANIC CONSTITUENTS OF THE URINE. 491 a reddish tint. Every cubic centimeter of silver-solution used corresponds to 10 mg. of sodium chlorid, or 0.00607 gram of chlorin. Phosphoric acid, about 2 grams daily, occurs in the form of mono- potassium and monosodium phosphate, and acid potassium and mag- nesium phosphate. It is present in larger amount after the ingestion of animal than of vegetable food. Its amount increases from the mid- day meal till evening, and it then declines in the night until the next morning. It is increased by muscular activity. It is derived in largest part from the alkaline and earthy phosphates of the food; and it is in part a metabolic product of lecithin and nuclein. In the presence of fever, the increased elimination of potassium phosphate is indicative of consumption of blood and muscle. When abnormal destruction of blood takes place suddenly in the body, the phosphoric acid, together with the urea, is greatly increased. In the state of hunger, the phosphoric acid is derived principally from the breaking down of the bones, which contain thirty times as much as the muscles. Also in the presence of cerebral meningitis, softening of the bones, diabetes and oxaluria, the elimination of phosphorus is said to be in- creased; likewise, after administration of lactic acid, morphin, chloral, or chloroform. It is diminished during pregnancy, on account of the formation of bone in the fetus. It is diminished also in consequence of the ingestion of ether and alcohol, and likewise of inflammation of the kidney. Qualitative Estimation. Potassium hydrate is added to urine in a test-tube, and heat is applied. The earthy phosphates are thus precipitated in a cloud, while the alkaline phosphates remain in solution. For qualitative estimation, there are necessary a titrated solution of uranic acetate, of which i cu. cm. unites with exactly 0.005 gram of phosphoric acid. To 50 cu. cm. of urine are added 5 cu. cm. of a solution of sodium acetate containing 100 grams of the latter salt and 100 cu. cm. of strong acetic acid diluted to i liter with water; and the mixture is heated. The titrating solution is permitted to flow with stirring so long as precipitation is apparent. As soon as free uranium oxid is present in the fluid, one drop of the mixture, to which a solution of potassium ferrocyanid is added upon a porcelain plate, yields a brownish-red reaction of uranium ferrocyanid. In addition to phosphoric acid, phosphorus occurs in the urine in an incom- pletely oxidized form, namely as glycerin-phosphoric 'acid, about 0.05 gram daily, in larger amount in the presence of nervous diseases and after chloroform- narcosis. Sulphuric acid is united in part with alkaline metals, in part with indol, phenol, skatol, and pyrocatechin, in the form of aromatic ethe- real sulphates, both in the proportion of i to 0.1045 on the average. All factors that favor the formation of indol, phenol, skatol, or pyro- catechin increase the conjugate ethereal sulphates. The total amount of sulphuric acid eliminated is from 2.5 to 3.5 grams daily. It is in- creased after the ingestion of sulphur. The sulphuric acid is derived principally from the decomposition of albuminates. It is increased by muscular activity; and, therefore, its amount is always parallel to that of the urea eliminated. The amount of alkaline sulphates ad- ministered with the food is, as a rule, exceedingly small. Increased excretion of sulphuric acid in febrile urine indicates increased tissue-metabolism in the body. In the presence of inflammation of the kidney a diminution has been observed, in cases of eczema a marked increase in the amount of sulphuric acid in the urine. In rabbits, but not in carnivora and human beings, administration of taurin, which contains sulphur, causes the pres- ence of an increased amount of sulphuric acid in the urine. According to Ziilzer, the relative amount of sulphuric acid in the urine is small when the secretion of bile in the intestine is large. The qualitative demonstration is made by addition of barium chlorid to the urine, which yields a fine, white, insoluble precipitate of barium sulphate. For quantitative estimation, 50 cu. cm. of urine are strongly acidulated with acetic acid and an equal volume of water and barium chlorid is added. After 492 THE INORGANIC CONSTITUENTS OF THE URINE. three-quarters of an hour's warming upon the water-bath, the precipitate will have been deposited. This is collected upon an ash-free filter, first washed out with water, then with warm dilute hydrochloric acid, and finally again with water. The barium sulphate thus purified is fused and weighed. It contains all of the sulphuric acid united with salts. The filtrate and the wash-water contain besides the conjugate sulphates. The combined fluid is mixed with one-eighth of its volume of concentrated hydrochloric acid and heated for a considerable time. Barium sulphate and a resinous mass separate out. The fluid is filtered, and the resinous mass is dissolved and washed from the filter with hot alcohol, and finally, again washed with hot water, then dried and fused. One part of barium sulphate corresponds to 0.3433 sulphuric acid. In addition to sulphuric acid, sulphur (one-fifth) occurs in the urine in an incompletely oxidized form (potassium sulphocyanate, cystin, and a sulphurous substance derived from the bile). Sulphurous acid, constant in carnivora, occurs in normal human urine only when hydrogen sulphid is formed in the intestine in considerable amount. Hydrogen sulphid, which is less commonly observed, is abnormal. It is recognizable by the black discoloration of paper moistened with lead acetate and ammonia when held over the urine. It results principally through fermentation by bacteria (bacterium coli) , and is rarely absorbed from the intestine or from pathological putrid foci. Small amounts of silicic acid and nitric acid, derived from drinking- water, the latter, however, in part produced in the body itself, are present. In the fermentation of urine, the nitrates are reduced to nitrites. After the administration of salts of the vegetable acids, car- bonates appear in the urine, which then effervesces upon addition of an acid. Sodium in the urine is principally united with chlorin, and in lesser degree with phosphoric acid and uric acid. Potassium, equaling about one-third of the sodium, is combined principally with chlorin. During fever, more potassium is excreted than sodium, while the reverse occurs during convalescence. Calcium and magnesium are present in normal acid urine dissolved as chlorids or acid phosphates. If the urine be- comes neutral, neutral calcium phosphate and magnesium phosphate are precipitated. The latter has been found also in alkaline urine in association with disorders of the stomach, in the form of large, trans- parent, four-sided prisms. If the urine becomes alkaline, calcium car- bonate (Fig. 172, a), or amorphous tribasic calcium phosphate is pre- cipitated, the magnesium, however, in the form of ammonio-magnesium phosphate (triple phosphate). The calcium is derived from food, and its amount varies in accordance with the digestive and absorptive capability of the digestive tract. In the presence of pulmonary tuber- culosis and diabetes, the excretion of calcium is increased. Free ammonia, from 0.06 to 0.88 gram in the day, occurs also in quite fresh urine, and in larger amount with animal than with vegetable food. After administration of mineral acids, the excretion of com- bined ammonia likewise increases. The appearance of an increased amount of ammonia indicates a predominance of acids in the body and a deficiency of alkalies. Demonstration: A strip of red litmus-paper held over a mixture of urine and milk of lime in a covered glass becomes blue. The alkaline combinations of the organic acids diminish the excretion of ammonia. Inorganic ammonia-combinations are trans- formed into organic combinations, perhaps into an ammonium albu- minate. Iron is never wanting in the urine, from 2.5 to 10 mg. being excreted daily. Further, some hydrogen dioxid is present, and is recognized by discoloration of a solution of indigo on addition of an iron sulphate. ACID AND AMMOXIACAL URINARY FERMENTATION. 493 One liter of urine contains 24.4 cu. cm. of gases; TOO volumes of urinary gases obtained by exhaustion contain 65.40 volumes of carbon dioxid, 2.74 volumes of oxygen, and 31.86 volumes of nitrogen. After vigorous muscular activity the amount of carbon dioxid may be doubled. The act of digestion also causes an increase, while drinking in large amount causes a reduction. SPONTANEOUS ALTERATIONS IN THE URINE ON STANDING; ACID AND AMMONIACAL URINARY FERMENTATION. When kept in a cool place, normal urine often exhibits a forma- tion of newly developed acid acid urinary fermentation. This results in consequence of the development of peculiar fermentative microor- ganisms, both budding-fungi, as well as fission-fungi, and is ac- companied by excretion of uric acid (Fig. 153, c), acid sodium urate (b), and calcium oxalate (d). The nature of the fermentative process is not as yet entirely known. Ac- cording to Briicke, lactic acid is formed from the / v g*& ^/l -*/'$ ' yj.?; \^~ S-ftA* '* < X-*l f ^ d - ... b FIG. 153. Sediment due to Acid Urinary Fermentation: a, fer- mentative budding-fungi; b, amorphous acid sodium urate: c, uric acid; d calcium oxalate. sugar of the urine ; accord- ing to Scherer, the germs decompose the vesical mu- cus and some urinary pig- ment into lactic and acetic acids. According to Roh- mann, who observed acid fermentation develop only exceptionally, this is due to acids that result from the decomposition of sugar and of alcohol accidentally present. Also the occur- rence of butyric and formic acids as products of the decomposition of other constituents of the urine has been observed. These newly formed acids expel the uric acid from the simple sodium urate, so that free uric acid and neutral sodium biurate (acid sodium urate) must be formed. With the commencement of acid fermentation, the urine appears to absorb oxygen. Even while the urine has an acid reaction, it becomes turbid and exhibits the presence of nitrous acid, whose source is as yet undetermined. The presence of nitrites is dis- closed by the development of an intensely yellow color on addition of potassium ferrocyanid and acetic acid. According to v. Voit and Hoff- mann, phosphoric acid is detached from acid sodium phosphate, with the formation of the basic salt, and partly displaces uric acid from sodium urate and partly causes its transformation into biurate. On standing for some time, and more readily when exposed to heat, the urine eventually undergoes ammoniacal fermentation (Fig. 154), the urea being decomposed, with addition of water, into carbon dioxid and ammonia, as a result of the development of the micrococcus and the bacterium urese (Fig. 155), at times arranged like a string of 494 ALBUMIN IN THE URINE. pearls. The ammonia is recognizable both from its odor and from the vapor that forms when a rod moistened with hydrochloric acid is held over the urine. The capability of decomposing urea is possessed besides by various other bacteria, including the staphylococci and the pulmonary sarcinae, whose germs float everywhere in the air. These organisms produce a soluble ferment that decomposes urea. Miquel describes ten microorganisms that decompose urea and uric acid. In consequence of the presence of the ammonia formed in the urine, the latter becomes turbid because substances are precipitated that are no longer capable of being held in solution, namely amorphous tribasic calcium phosphate; acid ammonium urate (Fig. 154, a) in the form of thorn-apple or morning-star spherules; and, finally, the large, clear, coffin-lid shaped crystals of ammonio-magnesium phosphate (6). There are formed, also, volatile fatty acids, principally acetic acid (from the carbohydrates of the urine). In the presence of catarrhal and inflam- matory conditions of the bladder, the fermentative process may take place within this viscus. Under such circumstances, however, leukocytes (pus-corpuscles, Fig. 1 60), and desquamated epithe- lial cells are admixed in con- siderable amount. When pus is present in large amount, the urine becomes albuminous. Rarely, free gases form in the bladder (pneumaturia), as, for FIG. 154. Sediment due to Ammoniacal Urinary Fermen- tation: a, acid ammonium urate; b, ammonio-mag- nesium phosphate. FIG. 155. Micrococcus ureae. instance, in consequence of the entrance of the bacterium lactis aero- genes (Fig. 126, 2). A bacillus generating hydrogen sulphid (bacterium coli commune) and one generating methylmercaptan, have also been found. ALBUMIN IN THE URINE: PROTEINURIA, ALBUMINURIA. For the physician, albumin is a most important abnormal constituent of the urine. (i) Serum-albumin (whose properties are described on pp. 73 and 458) may appear in the urine in the absence of anatomical alteration in the structure of the kidney, and the condition has been designated by Leube as physiological albu- minuria. Albumin has often been found normally in the urine in minute traces, particularly in consequence of the presence of a considerable amount of albumin in the blood-plasma (as, for instance, when the secretion of milk is suppressed) and after a meal containing an excess of proteid. Albumin is common, also, in the urine of the fetus and the new-born. (2) When the pressure in the distribution of the renal vessels is increased (as, for instance, after a cold bath or after excessive ALBUMIN IN THE URINE. 495 drinking of fluids), either for a considerable time or as a transitory phenomenon, particularly in association with hypostatic hyperemia attending diseases of the heart, emphysema, chronic pleural effusions, infiltrations of the lungs; and after compression of the chest that causes stasis in the pulmonary circulation, and finally extends into the renal veins. (3) After division or paralysis of the vaso- mptor nerves of the kidney, in consequence of which intense hyperemia of the kidney is brought about. In this category belongs the albuminuria following severe and protracted painful affections of the abdominal viscera, as, for instance, strangulated hernia, in consequence of which reflex paralysis of the nerves of the renal vessels is induced. After severe muscular exertion, as in marches, parturi- tion, or convulsive seizures, in cases of epilepsy, eclampsia, the convulsions attend- ing suffocation and strychnin-poisoning. The albuminuria observed in conjunc- tion with concussion of the brain, apoplexy, and spinal paralysis, severe emotional disturbances, excessive mental activity, and morphinism, is possibly attributable to a disorder of the vasomotor centers. (4) Inability en the part of the epithelial cells to restrain the albumin may cause albuminuria; and, as it appears, in conse- quence of defective nutrition and functional debility of the secretory elements. In this category belongs the albuminuria attending ischemia, and that following hemorrhage and attending anemic conditions, scorbutus, icterus, diabetes, and the death-agony. (5) In association with many acute febrile diseases, especially the acute exanthemata (as, for instance, scarlet fever); further, typhoid fever, pneumonia, and pyemia. It is probable that under such circumstances the secre- tory apparatus of the kidney has undergone changes (cloudy swelling of the epithe- lial cells of the urinary tubules, inflammation of the glomeruli) ' that render these incapable of preventing the escape of the albumin. (6) Degeneration of the kidneys, such as contraction of the kidneys, amyloid degeneration, further inflammatory processes in their various stages, are generally attended with albuminuria. Sem- mola has shown that the albuminuria attending nephritis is not rarely dependent rather upon the state of the blood than upon the disease of the kidneys. He believed that the renal lesion occurs in general as a secondary phenomenon, while the albuminuria is primary, except the form that is a result of the inflammation of the kidney itself. (7) Finally, inflammatory and suppurative processes in the tirinary passages, from the pelvis of the kidney to the extremity of the urethra, may cause albuminuria. Under such circumstances, however, leukocytes are always found in the urine; not rarely, also, erythrocytes or the products of their solution, and fibrin-coagula. Certain substances that give rise to irritation and inflammation of the urinary apparatus should finally be mentioned, such as can- tharides and carbolic acid. (8) The appearance of albumin in the urine after sodium chlorid has been entirely eliminated from the food is noteworthy. The albumin disappears when the salt is resumed. Demonstration of Albumin in the Urine. (a) After strong acidulation with acetic acid, a few drops of a concentrated solution of potassium ferrocyanid causes a precipitate. (b) Urine to which is added one-third its volume of pure nitric acid exhibits a precipitate. A resulting turbidity may be due, apart from albumin, to the precipitation of urates. Slight heat, however, causes solution of the latter, while albumin remains turbid. (c) Urine to which a few drops of acetic acid are added and which is then mixed with an equal volume of concentrated sodium sulphate and boiled yields a precipitate. (d) The urine is acidulated with a few drops of concentrated acetic acid, and filtration is practised for the removal of mucin. The urine is then cautiously overlaid, drop by drop, in a test-tube held obliquely, by the following mixture: Mercuric chlorid, 8; tartaric acid, 4; glycerin, 20; water, 200. Turbidity results at the line of contact. Albumose is disclosed by the same reaction, but it is redissolved by heat. Jolles recommends the following mixture: Ten parts of mercuric chlorid, 20 parts of succinic acid, 10 parts of sodium chlorid, and 500 parts of water. Five cubic centimeters of filtered urine are acidulated with i cu. cm. of 30 per cent, acetic acid and 4 cu. cm. of the reagent described are added. (e) A few drops of 30 per cent, sulphosalicylic acid are added to filtered urine. This reaction discloses also the presence of albumoses, but the precipitate due to the latter is cleared up on heating. Boiling, by driving off the carbon dioxid. may cause a precipitate of earthy phosphates in alkaline urine, and this may simulate albumin. If. however, a small amount of acetic acid be added, the phosphates are redissolved, while albu- 496 ALBUMIN IN THE URINE. min would be coagulated. Only small amounts of clear urine should be employed in making the tests for albumin. Turbid urine, therefore, should first be filtered. The quantitative estimation of albumin is made as follows: 100 cu. cm. of urine, if necessary after addition of a small amount of acetic acid, are heated in a dish to the boiling-point, with the result that the albumin is precipitated as a flocculent deposit. The precipitate is collected upon a weighed, ash-free filter, dried at 110, and it is washed repeatedly with hot water, then with alcohol, and is thoroughly dried in the air-bath at 110. The dried filter is now weighed, and the weight of the filter is deducted. Finally, the filter with the albumin is reduced to ash in a weighed platinum crucible, and the weight of the ash is sub- tracted. For the estimation by the polarization-apparatus, reference may be made to p. 268. By means of Esbach's albuminimeter. A glass cylinder is filled with urine to the mark U, and with the albumin-precipitating reagent (20 parts of citric acid, 10 parts of picric acid, 970 parts of water) to the mark R, and is then closed with a stopper and agitated. After the lapse of twenty-four hours (at room-temperature) the coagu- lated albumin will have settled to the bottom. The divisions of the scale on the glass indicate the number of grams of albu- min in 1000 grams of urine. The urine must have an acid reaction, be fresh, and its specific gravity should not be too high. The presence of an excessive amount of albumin also may therefore require dilution of the urine with from 2 to 4 times as much water. The amount of albumin obtained is then naturally to be multiplied by 2 or 4. Globulin has been found almost exclusively in albuminous urine; and, indeed, in the majority of cases. To demonstrate its presence, 50 cu. cm. of albuminous urine are rendered feebly alkaline with potassium hydrate, and powdered magne- sium sulphate is added to an amount approximating some- what more than 24.11 per cent. If exposed to a warm tem- perature, all of the globulin is precipitated in the course of twenty-four hours, and it can be filtered out, dried, and weighed. With this the total amount of albumin should be compared. The presence of globulin is of unfavorable prog- nostic significance. Its amount is diminished by favorable circulatory conditions in the kidney. Propeptone (Albumose). Peptone does not occur in the urine. What has previously been described as such is pro- peptone. The latter occurs sometimes in acid, albuminous urine; rarely, also, in urine free from albumin. Maixner found it constantly in connection with all suppurative dis- orders, empyema, peritonitis, pneumonia, meningitis, ulcer- ative affections of the digestive tract, etc. pyo genie propcp- tonuria. Albumose is always present also in pus, and propep- tonuria is a sign of the destruction of pus-corpuscles. It oc- curs further in connection with increased retrogressive or de- structive processes in tissues rich in albumin; as, for instance, in the presence of carcinoma and of fever. In the same category probably belongs also its constant occurrence in the puerperium; often, also, during pregnancy, when the fetus has died and is undergoing putrefaction puerperal propcptonuria. Pro- peptone is found, also, when the urine contains semen. Demonstration. Ten cu. cm. of urine are heated with 8 grams of ammo- nium sulphate until the latter is dissolved. Then the hot fluid is centrifugated for a minute. The fluid is decanted, the residue rubbed up with 97 per cent, alcohol for the removal of the urobilin, then dissolved in a small amount of water, and boiled and filtered. The filtrate is subjected to the biuret-test. When the urine contains hematoporphyrin, it is advisable to precipitate this first with barium chlorid. Egg-albumin appears after generous ingestion of fluid egg- albumin, as well as after injection into the tissues or into the blood-stream. Mucus is present in association with catarrhal conditions of the urinary organs, particularly of the bladder. Microscopically, the presence of numerous leukocytes is noteworthy. As these contain albumin the intensity of the reaction for albumin will vary with their abundance. The characteristic reagent for mucus, however, FIG. 156. Esbach's Al- buminimeter. BLOOD AND HEMOGLOBIN IN THE URINE. 497 is acetic acid, which produces a flocculent sediment also in clear filtered urine. Mucin, however, is not precipitated by boiling. The mucoid substance, nucleo- albumin, which is precipitated by an excess of acetic acid in dilute urine, occurs as a sign of renal irritation. In the presence of disorders of the bladder, there rarely occurs in the urine an admixture of a peculiar ropy, gum-like substance, consisting of transformed mucus, which is thought to be the product of an anaerobic bacterium gliscro- genum. Nucleoalbumin also has been found, derived partly from the bladder, partly from the urinary tubules of the medullary structure; it is precipitable by acetic acid. Kolisch and Burian found histon in a case of leukemia, and Jolles nucleohiston. According to Morner, the urine contains substances that precipitate albumin, such as chondroitin-sulphuric acid, nucleinic acid, rarely taurocholic acid, in larger amount in association with jaundice. If acetic acid be added to normal urine, these substances are eventually precipitated out. BLOOD AND HEMOGLOBIN IN THE URINE: HEMATURIA, HEMOGLOBINURIA. In case of hematuria the blood may be derived from any portion of the urinary- apparatus. ( i) In case of hemorrhage from the kidney, the blood is generally admixed with the urine in small amount and is well distributed. The erythrocytes under such circumstances often exhibit peculiar alterations in shape, and processes of division, which may be brought about by the action of the urea, and which have been attributed by Friedreich to independent ameboid movement (Fig. 159). The blood-cylinders present in the sediment are pathognostic of renal hemorrhage, that is, elongated microscopic coagula of blood, which must be considered as actual casts of the collecting tubules of the kidneys, and which are washed thence into the urine (Fig. 166). (2) In case of hemorrhage from the ureters, long, worm- like strings of coagulated blood are occasionally observed in the urine as casts o o*r FIG. 157. Thorn-apple shaped Blood-corpuscles in FIG. 158. Peculiar Changes in the Shape of the Rod the Urine. Blood-corpuscles in Case of Renal Hematuria (after Friedreich). of the ureter. (3) Relatively the largest coagula of blood occur in cases of hemor- rhage from the bladder. (4) Blood is present in the urine as an admixture at every menstrual period. Urine containing blood should always be examined microscopically for blood- corpuscles. In addition, attention should be given to ribrin-coagula. In acid urine, erythrocytes can be recognized for as long as two or three days; though never arranged in rouleaux. If the hemorrhage has been considerable, the cor- puscles are generally normal in shape. If, however, the urine is concentrated, they appear mulberry or thorn-apple shaped (Fig. 157). The blood-corpuscles always settle gradually to the bottom in urine at rest. If the blood is slowly admixed with the urine and in small amount from ruptured capillaries, the erythrocytes appear of variable size, some not larger than between one-eighth and one-half of the normal (Fig. 159). At the same time, their pig- ment has become brownish yellow in color (methemoglobin) . If, in a case of hemorrhage of this kind, there exists catarrhal inflammation of the bladder, numerous leukocytes, at times adherent to one another (Fig. 160), which, 32 498 BLOOD AND HEMOGLOBIN IN THE URINE. FlO. 159. Red and White Blood-corpuscles of Varying Size. in fresh preparations, often exhibit distinct ameboid movement, are found among the erythrocytes, which often are greatly shrunken. If the urine, as is usual, is of alkaline reaction, crystals of ammonio -magnesium phos- phate will be present (Fig. 160) . If the erythrocytes have al- ready become pale, they are not rarely rendered more dis- tinct by addition of a wine- yellow solution of iodin and potassium iodid. Hemoglobinuria, that is, the elimination of hemoglobin through the urine, is entirely distinct from true hematuria. It occurs only when a consider- able amount of hemoglobin has already been set free in the vessels from dissolved red blood-corpuscles (hemocytoly- sis). This is observed in its purest form after transfusion of blood from an animal of a different species, and also from lambs' blood in human beings. The foreign blood-corpuscles are dissolved in the blood- stream of the recipient and the hemoglobin appears in the urine . In addition , microscopic casts of the urinary tubules of coagulated globulin-like substance, stained yellow by hemoglobin, are present. Hemoglobin has been found in the urine, also, after extensive burns; after decomposition of blood in the body in cases of pyemia, scorbutus, purpura, severe ty- phoid fever ; after the ingestion of unboiled toad-stools, and of lupins by sheep; after inhala- tion of hydrogen arsenid ; after the entrance of azobenzol, naphthol, pyrogallic acid, to- luylendiamin, potassium chlor- ate, chloral, phosphorus, or car- bolic acid, into the circulation, as these bodies dissolve the erythrocytes; and, finally, periodically in attacks (in the horse also) of as yet unex- plained nature, in which the condition appears to depend upon undue solubility of the erythrocytes, particularly from the action of external cold upon the skin. Demonstration of Blood in the Urine. i. The color of urine containing blood has been observed to be of all shades, from light red to dark FIG. 160. Greatly Shrunken Red Blood-corpuscles in the Urine from a Case of Catarrh of the Bladder, in the midst of numer- ous Leukocytes and small Crystals of Triple Phosphates. brownish-black, in accordance with the amount of blood present. Often the urine is turbid. 2. Urine containing blood or hemoglobin must always exhibit the reactions of album^n. 3. Heller's blood-test: To urine in a test-tube, one-third potassium hydrate is added and moderate heat is applied. The earthy phosphates are precipitated, BLOOD AND HEMOGLOBIN IN THE URINE. 499 and carry down with them hemochromogen, so that garnet-red flakes are de- posited. When the urine contains but a small amount of blood, these flakes appear red in reflected light and greenish in transmitted light, the distinction being clear when as little as one part of hemoglobin is present in a thousand. If the earthy phosphates are already precipitated in alkaline urine, deposition is effected artificially by addition of a few drops of magnesium sulphate and ammonium chlorid, and the same change in color is apparent. 4. From the earthy phosphates thus obtained, containing hemoglobin, and collected upon a filter, hemin-crystals can be prepared. For this purpose the same procedure may be followed as is described on p. 62. 5. The reaction may be tested, also, with tincture of guaiac and oil of tur- pentine, the blood acting as a carrier of ozone. The urine should not lose the property of developing a blue color as a result of previous heating. 6. Urine containing blood when examined with a spectroscope exhibits characteristic appearances. The arrangement of the apparatus is shown in Fig. 161. The urine is placed in the chamber D (hematinometer) i cm. thick, with parallel glass walls. Through this pass the rays of light from a lamp, E, while FIG. 161. Spectroscope for Examination of the Urine as to the Presence of Hemoglobin. another, F, illuminates a scale, and the observer makes his observation through the telescope, A. The examination yields the following results: (a) Fresh urine containing blood exhibits the spectrum of oxyhemoglobin (Fig. 15). Under some circumstances, it is necessary, in this connection, to dilute the urine with distilled water and to secure perfect clearness by filtration. To con- firm the observation, the oxyhemoglobin may be exposed to the action of reducing substances, which produce reduced hemoglobin. (6) If concentrated urine containing blood is permitted to stand for a some- what longer time, especially at the temperature of the blood, it acquires a deep, dark-brown color, like coffee-grounds, in the presence of an acid reaction. The hemoglobin is thus converted into methemoglobin. Methemoglobin in solution is, in contradistinction from oxyhemoglobin, precipitable by lead acetate. The acid solution of methemoglobin in urine thus resulting exhibits in the spectroscope a close resemblance to hematin in acid solution (Fig. 15). If the urine is now rendered alkaline, the absorption-bands of methemoglobin in alkaline solution appear. The spectra of oxyhemoglobin and methemoglobin are also found com- bined in the urine. When treated with reducing substances methemoglobin is transformed into hemoglobin. Later on, also hematin is present in acid solution in the urine. If such urine is treated with reducing substances, alkaline hematin appears. 500 BILIARY CONSTITUENTS IN THE URINE. Traces of hematoporphyrin are constant in the urine, btit in considerable amount this substance is, however, rare (in cases of lead-poisoning, intestinal hemorrhage, administration of sulfonal). Demonstration. To 500 cu. cm. of urine are added 100 cu. cm. of a ten per cent, sodium-hydrate solution. The precipitate is washed upon a filter, dissolved in hydrochloric-acid alcohol, and exhibits spectroscopically acid hematoporphyrin. (c) If urine containing blood is coagulated by boiling and the brownish-black coagulum is washed out and dried, and then extracted at gentle heat with alcohol containing sulphuric acid, a brown fluid is obtained, which, if sufficiently concen- trated, proves on spectroscopic examination to be hematin in acid solution (Fig. 15,5). BILIARY CONSTITUENTS IN THE URINE: CHOLURIA. The physiological factors that are of importance in connection with the pres- ence of biliary matters in the urine have been in part already discussed (p. 319). If bilirubiii is formed from hemorrhagic extravasations through the activity of the connective-tissue cells, bile-pigment may pass over into the urine, while the tissues acquire a yellow color. Cases presenting this peculiarity have been designated instances of hematogenous or anhepatogenous icterus. The biliary coloring-matters are demonstrated by the Gmelin-Heintz test (P 3 J 7-) ! the appearance of the green color-ring of biliverdin can be considered as characteristic. The method has received several modifications, (i) If a consid- erable amount of icteric urine is passed through filter-paper, one drop of nitric acid with nitrous acid yields the color-rings upon the inner surface of the yellow- colored, and, if necessary, warmed, filter. (2) If 50 cu. cm. of icteric urine, acidu- lated with acetic acid, be agitated with 10 cu. cm. of chloroform, bilirubin passes over into the latter. If bromin-water be added, beautiful color-rings appear. If to the chloroform-extract oil of turpentine containing ozone be added, together with a little dilute potassium hydrate, a green color due to biliverdin appears in the watery solution. (3) Tincture of iodin diluted ten times with alcohol and overlaid on the urine gives rise to a grass-green ring. (4) According to Jolles, the following procedure yields the most distinct results: To 50 cu. cm. of urine are added 5 cu. cm. of a ten per cent, solution of barium chlorid and 5 cu. cm. of chloroform, agitation being practised for four minutes in a vessel closed with a glass stopper. After the lapse of ten minutes chloroform and precipitate are pipetted into a dish, placed over the water-bath at a temperature of 80 until evaporation takes place. The mixture is then permitted to cool. Now one or two drops of concentrated nitric acid are permitted to flow upon the precipitate at several places, and the color- rings appear. (5) The urine is rendered alkaline with soda, and calcium chlorid is added drop by drop until the fluid overlying the precipitate appears normal. The precipitate is filtered off and washed, over it is poured alcohol, and it is dissolved by means of hydrochloric acid. If the solution be boiled, a color varying between green and blue develops. When cooled, it yields a play of colors from blue to violet to red with nitric acid. In the presence of protracted high fever, the urine at times contains only biliprasin. If it contains only choletelin, the urine, to which hydrochloric acid has been added, is examined with the spectroscope, and a pale absorption-band will be found between b and F. Hematoidin-crystals (Fig. 92, b) are present in the urine when erythrocytes are destroyed in the blood-stream in large number. After these had been found first by v. Recklinghausen and Landpis, after transfusion of heterogeneous blood, they were observed in conjunction with various infectious diseases that exercise a destructive effect upon the erythrocytes; in cases of scarlet fever; in lesser degree in cases of typhoid fever; ' and Landois with Strubing observed them in the urine in association with attacks of periodic hemoglobinuria. Landois refers the biliary acids often observed by him in the urine after solution of the erythrocytes to the hemoglobin of the destroyed corpuscles. If old collections of blood rupture into the urinary passages, as in cases of pyonephrosis or in conjunction with the perforation of necrotic areas, the appearance of the crystals is comparable to that in the sputa in analogous cases. In cases of hypostatic icterus, bilirubin, which is identical, was found in crystalline form. The biliary acids, which Dragendorff demonstrated to the extent of 0.8 gram in 100 liters of normal urine, appear in larger amount in connection with resorption- icterus, although even under such circumstances never in considerable amount. SUGAR IN THE URINE. 501 Landois observed them, also, in association with the passage of biliary matters in consequence of marked destruction of erythrocytes. Their properties and reaction have already been described (p. 315), a solution of cane-sugar 0.5 gram to one liter of water being employed for the latter. Urine of low specific gravity should be concentrated upon the water-bath. To insure absolute certainty, a portion of urine is evaporated over the water-bath almost to dryness, and the residue extracted with alcohol. The alcoholic extract is again carefully evaporated in a porcelain dish, and the residue dissolved in a few drops of water and sub- jected to Pettenkofer's test. If the test is applied directly to the urine, one must previously have convinced himself that the urine is free from albumin, as this substance yields a similar reaction. In such an event the albumin should be removed by boiling and filtration. If filter-paper is dipped into urine to which cane-sugar has been added, and the paper is dried and brought in contact with sulphuric acid, a violet-red color results, which is particularly pretty in transmitted light. SUGAR IN THE URINE: GLYCOSURIA. Normal urine contains traces of dextrose. Small amounts of sugar are present after ingestion of sugar in large amounts (alimentary glycosuria) , and also in the presence of fever, after the drinking of beer supplemente'd by alcohol, occasionally in the exceedingly obese, in neurasthenics, in association with cerebral disease, and in advanced age. Glycosuria occurs also as a result of failure in intestinal activity in ill-nourished individuals; and, artificially, after ligation of the mesen- teric arteries. Dextrosuria of considerable degree is a sign of diabetes mellitus. In this connection, the large amount of urine, up to 10,000 cu. cm., as well as the high specific gravity, from 1030 to 1040, are striking. The diabetic patient excretes a relatively larger amount of water through the kidneys; and, on the other hand, a relatively smaller amount through the skin (and the lungs?) than a healthy person. Also the elimination of the water ingested takes place later and more uniformly than in health. The urine is pale yellow in color, although the amount of coloring-matter is, in the aggregate, by no means diminished; and the nitrogenous matters are increased. A diet of carbohydrates generally in- creases the excretion of sugar; while a proteid diet may reduce it. Uric acid and calcium oxalate are often found increased at the commencement of the disease. On standing for a considerable time yeast-cells constantly develop in the urine. For quantitative estimation the tests for sugar already described (p. 268) are appropriate, although the urine must be free from albumin or be rendered so. The following tests are most to be recommended: (a) The fermentation-test is the most reliable. A test-tube inverted over mercury is filled with the saccharine urine and a piece of yeast, living and free from sugar, as large as a pea, and also one drop of tartaric acid, are added, and the mixture is kept in a warm place. Carbon dioxid collects at the bottom of the inverted tube, and disappears after the introduction of potassium hydrate. (b) A 2.5 per cent, solution of copper sulphate and a solution containing 10 parts of sodiopotassic tartrate in 100 parts of a 4 per cent, solution of sodium hydrate are employed. Five cubic centimeters of urine are boiled in a test-tube, and from i to 3 cu. cm. of the copper-solution and 2.5 cu. cm. of the tartaric- acid solution in a second test-tube. The boiling of both fluids is interrupted simultaneously, and after the lapse of from 20 to 25 seconds, the contents of the one tube are poured without agitation into the other; reduction then takes place spontaneously . (c) Bottger's test with Nylander's modification (p. 267). (d) In the application of the phenylhydrazin-test, 5 cu. cm. of urine are diluted with 5 cu. cm. of water, and 0.5 of phenylhydrazin hydrochlorate and i gram of sodium acetate are added. The mixture is boiled for two minutes over the water-bath, is permitted to cool slowly and to stand for four hours in the cold. Combinations of glycuronic acid form similar, though plumper, crystals, more like thorn-apples. (e) In applying Molisch's test, -naphthol dissolved in chloroform, instead of in alcohol, is employed. The test discloses the presence of all of the carbohy- drates in the urine, under normal circumstances 0.96 per cent, altogether, of which o. i is grape-sugar. Urine containing sugar should be diluted 100 times. (/) If to 10 cu. cm. of diabetic urine in a test-tube 0.5 mg. of powdered gentian- violet are added, the urine is colored, while normal urine is not. 502 SUGAR IN THE URINE. Quantitative estimation is made by fermentation or by the titration-method. The estimation by circumpolarization is, according to Worm-Muller, almost value- less for the estimation of the amount of sugar in diabetic urine, as the urine often contains in part as yet unknown optically active substances. If, however, it be desired to employ this method, the urine must be previously agitated with commercial animal charcoal and filtered, in consequence of which it becomes colorless. Small amounts of glycogen derived from urinary tubules that have undergone glycogenic degeneration have been found by Leube in diabetic urine. After ingestion, the sugars that are most readily decomposed pass with greatest difficulty, while those that are not at all decomposable pass most readily, into the urine. If, therefore, considerable amounts of dextrose are administered, a portion thereof passes into the urine; and a larger amount in cases of diabetes than in health. Ingested levulose does not increase the amount of sugar in the urine of a diabetic patient. The use of starch in considerable amounts never gives rise to the presence of sugar in the urine in health, although it increases the amount of sugar in cases of diabetes. The ingestion of cane-sugar or of milk- sugar in considerable amount causes the passage of small amounts of each into the urine during health. The diabetic, under such circumstances, excretes an increased amount of dextrose. According to Kulz, the cane-sugar ingested by a diabetic patient is decomposed into grape-sugar and fruit-sugar; the latter is consumed in the body, the former in part excreted. The same takes place with milk- sugar. Levulose is rarely present in the urine, constituting levu- losuria. In severe cases of diabetes mellitus, Kulz found levorota- tory fi-oxybutyric acid, the next higher analogue of lactic acid, in the urine, from the oxida- tion of which diacetic acid is produced. The latter, in its turn, is readily decomposed into carbon dioxid and acetone. /3-oxybutyric acid is never wanting when diabetic coma is present. Acetone is present in the urine of diabetics often in considerable amount, princi- pally in association with pro- gressive loss of strength, and often even in spite of admin- istration of carbohydrates. From oxybutyric acid there results, by dehydration, a-cro- tonic acid, which Stadelmann found in diabetic urine. As albuminuria results from administration of acetone, the complication of albuminuria with diabetes is clear. Milk-sugar lactosuria is present in the urine of puerperal women, together with glucose and isomaltose, chiefly in connection with milk-stasis. The condition is thus due to absorption from the breasts. Milk-sugar likewise appears in the urine of infants with derangement of digestion. Pentose has, on several occasions, been observed in the urine: pentosuria. This substance contains 5 atoms of carbon, is not susceptible of fermentation, and is capable of causing reduction. It may possibly be due to disease of the pancreas. Phloroglucin and hydrochloric acid yield a red color. Pentose is present in coffee, in many wines, and in varieties of milk and sugar. Ingested pentoses arabinose, xylose pass over into the urine. Reichart has called attention to the simultaneous appearance of dextrin in urine containing sugar. Inosite has been found both in cases of diabetes and in cases of polyuria and albuminuria. Traces of it are contained even in normal urine. _ Occasionally, "sugar-puncture" in animals is followed by the appearance of inosite instead of dextrose in the urine. For the detection of inosite, the dextrose is removed by fermentation, and albumin by boiling after addition of a few drops of acetic acid and sodium sulphate. Of the filtrate, a few cubic FIG. 162. A, crystals of cystin; B, of calcium oxalate; c, hour- glass shaped crystals of calcium oxalate. CYSTIN, LEUCIN, TYROSIN. 503 centimeters are evaporated in a porcelain dish. down to a few drops; then 2 drops of a solution of mercuric nitrate (titration-solution according to J. v. Liebig) are added. A yellow precipitate takes place. If this is spread out and further carefully heated to a point beyond desiccation, a dark-red color appears, which on cooling gradually disappears. The sugar may, in rare cases, also give rise to pneumaturia, fermentation by microbes causing the development of carbon dioxid. CYSTIN. Cystin, C 6 H 12 N 2 S 2 O 4 , is a levorotatory body that occurs normally in [traces in the urine and but rarely in considerable amount. It appears in the form of colorless, six-sided plates (Fig. 162, A), in children also forming concretions. Cystin is insoluble in water, alcohol, and ether; readily soluble in ammonia, after the evaporation of which it crystallizes out. According to Baumann and Preusse, there exist intermediary products of metabolism that contain the material necessary for the forma- tion of cystin. When the metab- olism is normal, these, however, undergo further change ; and their sulphur appears in the urine ox- idized as sulphuric acid. In rare cases this oxidation fails to take place; and then the sulphur ap- pears in the urine as cystin. In cases of phosphorus-poisoning the cystin is increased. LEUCIN, C 6 H 13 NOo, AND TY- ROSIN, C 9 H n N0 3 . Both of these bodies, whose development has been referred to in the consideration of pancreatic digestion, are present in traces in normal urine. They occur to- gether in somewhat larger amount in association with derangements in the function of the liver-cells (acute yellow atrophy of the liver, phosphorus-poisoning) . As the elimination of urea is generally diminished at the same time, it may be concluded that the liver is the seat of the formation of urea. Leucin, which separates either spontaneously in the precipitate or only after evaporation of an alcoholic extract of the inspissated urine, appears in the form of yellowish-brown spheres (Fig. 163, a a) , occasionally with concentric radiation or provided with fine points at the periphery. When heated dry leucin sublimes without fusing. Tyrosin forms silky, colorless sheaves of needles (Fig. 163, b 6). If a solution of tyrosin be boiled with Millon's reagent, there results at first a pretty red color, and shortly afterward a deep brownish-red precipitate. If tyrosin is gently heated with a few drops of concentrated sulphuric acid, it is dissolved with the development of a transitory deep-red color. If it now be diluted with water, and barium carbonate be added to the point of neutralization, the mixture boiled and filtered, and dilute iron chlorid added to the filtrate, a violet color appears. Dissolved in hot water, addition of quinone produces a red color. FIG. 163. a a, Lcucin-spheres; b b, tyrosin-sheaves; c, double spheres of ammonium urate. SEDIMENTS IN THE URINE. Both in normal, as well as in pathological urine, precipitates may form at the bottom of the vessel; and these are designated sediments. They are either organized or unorganized. 54 ORGANIZED SEDIMENTS. ORGANIZED SEDIMENTS. (A) Sediment of blood: derived from, erythrocytes and leukocytes (Figs. 157, 158, 159, 160), occasionally also shreds of tibrin (Figs. 6, 7). (B) Pus-corpuscles, in greater or lesser amount in association with catarrhal or inflammatory processes in the urinary passages, entirely resemble the leukocytes (Figs. 6, 7). Marked, persistent admixture of pus is indicative of profound parenchymatous suppuration; numerous mononucleated leukocytes, of disease of the kidneys. Demonstration. If the supernatant fluid be poured off and a bit of potassium hydrate be dissolved in the sediment, the pus is converted into a vitreous, ropy mass, later becoming more consistent (alkali-albuminate) . Mucus treated in this manner is dissolved into a thin fluid admixed with flakes. (C) Epithelial cells of varied shape and not always distinguishable as to the source whence they are derived. They are more abundant in the presence of catarrhal conditions in the parts in question. In the urine of women, pavement epithelial cells from the vagina are also present. The spermatozoids likewise are included among epithelial structures. (D) Lower forms of organisms. The freshly collected urine from healthy FIG. 164.-^, Molds; /, budding-fungi (yeast); d g, bacteria (micrococci and bacilli); a b c, uric acid (after v. Jaksch). FIG. 165. Epithelial Tube-casts. persons always contains many microorganisms, which, however, have probably been washed away from the urethral mucous membrane. They are principally large or small diplococci. In cases of gonorrhea, gonococci thus gain entrance into the urine. Lower forms of organisms may also appear in the urinary pas- sages, as, for instance, in the bladder, when their germs have been introduced by means of unclean catheters. The following varieties may be distinguished: 1. Schizomycetes (fission-fungi). In pathological cases bacteria may gain entrance into the urinary tubules and the urine from the blood. Bacterial cul- tures injected artificially into the vessels are in part eliminated through the kidneys. In urine undergoing alkaline fermentation, both micrococci and rod- shaped bacteria or bacilli appear (Fig. 164). The sarcinae are further included among schizomycetes. 2 . Saccharomycetes (fermentative germs) : (a) The germ of acid fermentation of urine (saccharomyces urinas) : small vesicular cells, arranged partly in groups, partly in rows (Figs. 153, a; Fig. 164, /). (6) Yeast (saccharomyces fermentum, Fig. 140) is present in diabetic urine. 3. Phycomycetes (molds) appear in putrid urine as mold-formations (Fig. 164, r). They are without significance. (E) Of great significance in the diagnosis of certain diseases of the kidney is the occurrence of so-called urinary cylinders, that is, casts of the urinary tubules. If these structures are relatively thick and rather straight, they are probably ORGANIZED SEDIMENTS. 505 derived from the collecting tubules of the kidney; while if they are thinner and tortuous, their source is suspected to be the convoluted tubules. ^ Various kinds of tube-casts can be distinguished: i. Epithelial casts (Fig. 165), which consist of coherent and desquamated cells of the urinary tubules. They indicate that no profound change has as yet taken place within the kidney, but that, as in catarrhal inflammatory states of mucous membranes, the epithelial cells are in process of desquamation. 2. Hyaline tube-casts (Fig. 171) are com- pletely homogeneous and transparent. They are most readily demonstrated by addition of a solution of iodin to the preparation. They are generally long and narrow; occasionally, they present fine disseminated points, or fat-granules (finely granular tube-casts, Fig. 169). They appear not to be derived from a transud.a- tion from the blood, but as a result of the secretory activity of the epithelial FTG. 166. Blood-casts. FIG. 167. Casts of Leukocytes (after v. Jaksch). FIG. 168. Acid Sodium Urate in the Form of Tube-casts. FIG. 169. Finely Granular Tube- casts. FIG. 170. Coarsely Granular Tube-casts (after v. Jaksch) FIG. 171. a. Hyaline tube-cast: b, hyaline tube-cast with leukocytes; c, hyaline tube- cast with renal" epithelium (after v. Jaksch). cells of the urinary tubules. 3. Darkly granular tube-casts (Fig. 170), brownish yellow, opaque, and consisting wholly of a granular mass, are usually somewhat wider than hyaline tube-casts. Marked variations of the latter occur. Not rarely, they exhibit fattily degenerated or atrophic epithelial cells of the urinary tubules. 4. Amyloid tube-casts occur in cases of amyloid degeneration of the kidneys. They have a waxy luster, are completely homogeneous (Fig. 171, u) and yield, with sulphuric acid and solution of iodin, the blue color of amyloid reaction. 5. Blood-casts, consisting entirely of coagulated blood, with distinct blood-corpuscles, occur in association with capillary hemorrhage into the tissue of the kidney (Fig. 166). These are allied to the casts found in connection with hemoglobinuria ; as, for instance, after transfusion of heterogeneous blood. They consist of hemoglobin or of its globulin tinged with hematin. The tube-casts stained yellow that have been observed in conjunction with icterus probably also result from the albumin of dissolved blood-corpuscles. Urine containing tube- casts is always albuminous. 506 SEDIMENTS IN THE URINE. Tube-casts of leukocytes are observed in connection with suppurative pro- cesses in the urinary tubules (Fig. 167). U rates arranged in the shape of tube- casts are without significance (Fig. 168); as well as cylindroids, formed of mucus, with which short strands of mucus arising in the ureter, the bladder, the prostate, the uterus, and the vagina, may be confounded. UNORGANIZED SEDIMENTS. The unorganized sediments, in part crystalline, in part amorphous, have already received consideration in the discussion of the individual constituents of the SCHEMATIC RESUME FOR THE RECOGNITION OF ALL OF THE SEDIMENTS IN THE URINE. I. In acid urine there may be found i. An amorphous crumbling sediment, (a) Which is soluble in the heat and is again precipitated in the cold, and which, on addition of a drop of acetic acid to the microscopic preparation, forms crystals of uric acid, which often has a reddish color (brick-dust powder) . This sediment consists of sodium or potassium biurate (Fig. 153). (6) The sediment is not dissolved by heat, but on addition of acetic acid, and without effervescence. This is probably tribasic calcium phosphate. (c) Highly refracting granules, occurring occasionally and soluble in ether. $ FIG. 172. a, Finely granular calcium carbonate; b and c, crystalline neutral calcium phosphate. are fat-globules. Fat occurs in the urine particularly in conjunction with the presence of a round-worm (filaria sanguinis hominis) in the blood (only in for- eigners or travelers) ; further, occasionally together with sugar in the urine, in tuberculous patients; in cases of phosphorus-poisoning, of yellow fever, of pyemia; after protracted suppuration; and, finally, after injections of fat or milk into the circulation. Fatty degeneration in some portion of the urinary apparatus, ad- mixture of pus from old abscesses, and severe injuries to bones, should further be taken into consideration. In this connection, attention should be given also to cholesterin and lecithin. Rarely, the amount of fat in the urine may be so marked as to give rise to a creamy appearance chyluria. 2 . A sediment consisting of crystals : (a) Uric acid (Fig. 148 and Fig. 153 whetstone-shaped crystals). (6) Calcium oxalate (Fig. 153, Fig. 162, B} envelop-shaped crystals, insolu- ble on addition of acetic acid. (c) Cystin extremely rare (Fig. 162, A). (d) Leucin and tyrosin of great rarity (Fig. 163). II. In alkaline urine there may be present: 1. The sediment is wholly amorphous and crumbling; it consists of tribasic calcium phosphate. It is soluble on addition of acids without effervescence. 2. The sediment is crystalline, or, at least, of characteristic form. URINARY CONCRETIONS. 507 (a) Ammonia-magnesium phosphate (Figs. 173, 160, 154): Large coffin-lid crystals, immediately soluble on addition of acids. (6) Small globules, yellowish in reflected light, dark in transmitted light, often provided with points; thorn-apple or morning-star shaped, together with amorphous granules (Figs. 154 and 175). These consist of acid ammonium urate. (c} Calcium carbonate: Small whitish globules, biscuit-shaped or arranged side by side in irregular masses, together with amorphous granules. Efferves- ft %.* FIG. 173. Ammonio-magnesium Phosphate. V # FIG. 174. Imperfectly Developed Crystals of Am- monio-magnesium Phosphate. FIG. 175. Acid Ammonium Urate (after v. Jaksch). FIG. 176. Basic Magnesium Phosphate. cence takes place on addition of acids, also in the microscopic preparation (Fig. 172, a). (d) Leucin and tyrosin are extremely rare (Fig. 163). Crystals of neutral calcium phosphate (Fig. 172, c), with their spear-shaped extremities in contact, are also rare, as well as plates of basic magnesium phosphate (Fig. 176). Organic sediments may occur both in acid, as well as in alkaline, urine. Among them, pus-corpuscles are present especially in alkaline urine, and the lower forms of vegetable organisms likewise predominate under such circumstances. URINARY CONCRETIONS. Urinary concretions vary in size from that of a grain of sand or a pebble to that of a fist. They are encountered in the bladder, also in the pelvis of the kid- ney, in the ureters, and in the prostatic sinus. All urinary concretions contain a framework of organic structure uniting the particles of the formation into a coherent mass. They are divided, according to Ultzmann, as follows: 1. Concretions whose nucleus consists of the sediment formed in acid urine primary calculus-formation. All of these arise primarily in the kidney and pass thence into the bladder, where they undergo enlargement in accordance with the development of the crystals in the urine. 2. Calculi that have for a nucleus either the sediments found in alkaline urine 508 URINARY CONCRETIONS. or a foreign body secondary calculus-formation. These develop in the bladder itself. Primary calculus-formation takes place from free uric acid in the form of sheaves as a nucleus (Fig. 148, 7), and surrounded by layers of calcium oxalate. Secondary calculus- format-ion takes place in neutral urine from calcium carbonate and crystalline calcium phosphate, in alkaline urine from acid ammonium urate, ammonio-magnesium phosphate, and amorphous calcium phosphate. Chemical examination next determines whether or not the particles of the concretion are combustible upon a platinum plate. I. Combustible concretions can consist only of organic matter. (a) If the murexid-test yields a positive reaction, the concretion contains uric acid. Uric-acid calculi are common, often of considerable size, smooth, rather hard, and in color from yellow to reddish brown. (b) If another specimen on boiling with potassium hydrate yields an odor of ammonia, and if moist turmeric-paper held in the vapor becomes brown, or a glass rod moistened with hydrochloric acid and held over the vapor yields fumes of ammonium chlorid, the concretion contains ammonium urate. If this test yields a negative result, the concretion contains pure uric acid. Calculi of ammonium urate are rare, generally small, of earthy consistence, and in color between clay- yellow and whitish. (c) Should the xanthin-reaction be positive, this substance is present, though it is rare. In one instance, indigo has been found in a calculus. (d) If cystin-crystals (Fig. 162, .4) are developed after solution in ammonia and evaporation of the latter, the presence of this rare substance is demonstrated. (e) Concretions composed of blood-coagula or fibrinous flakes, without any crystallization whatever, are rare. If burned, they yield an odor of singed hair. They are insoluble in water, alcohol, and ether. They are soluble in potas- sium hydrate, out of which they are reprecipitable by acids. (f) Urostealith is the name that has been given to the substance composing rarely found concretions which in the fresh state are soft and elastic, re- sembling India rubber. On drying, they become brittle and hard, and in color between brown and black. Warmth causes them to become softer again, and they melt when heated. Solution takes place in ether, the residue of the evapo- rated ethereal solution becoming violet in color on further heating. Urostealith is dissolved by heated potassium-hydrate solution, with saponification. Concre- tions containing fat or cholesterin are rare. II. If concretions are only in part combustible, with a residue, they contain organic and inorganic matters. (a) A portion of the calculus is reduced to powder, and this is boiled with water and filtered hot. Urates that may be present undergo solution. In order to determine whether the uric acid is combined with sodium, potassium, calcium, or magnesium, the filtrate is evaporated and fused. The ash is examined spectro- scopically (flame-spectra) , and by this means sodium and potassium are recognized. Magnesium urate and calcium urate are transformed by fusing into carbonates. In order to separate the two, the ash is dissolved in dilute hydrochloric acid, and filtration is practised. The filtrate is neutralized with ammonia; then again dis- solved with a few drops of acetic acid. Addition of ammonium oxalate precipi- tates calcium oxalate. Filtration is now practised, and to the filtrate are added sodium phosphate and ammonia. By this means the magnesia is separated as ammonio-magnesium phosphate. (b) Calcium oxalate occurs principally in children, either as small, smooth, pale hempseed-calculi, or in dark, nodular, hard mulberry-calculi. It is not affected by acetic acid, is soluble in mineral acids, without effervescence; and is reprecipitated by ammonia. When fused upon a platinum plate, the specimen becomes black; it is then burned white to calcium carbonate, which undergoes effervescence upon addition of acid. (c) Calcium carbonate occurs generally in whitish-gray, earthy, chalk-like, rather rare calculi that usually are multiple. It is soluble in hydrochloric acid with effervescence. . When fused, it becomes at first black, from admixture of mucus; but soon afterward white. (d) Ammonio-magnesium phosphate and basic calcium phosphate are usually united in soft, white, chalky stones, which at times attain quite considerable size. Such calculi imply a long sojourn in ammoniacal urine. The first substance yields an odor of ammonia when heated, and more distinctly when heated with potassium hydrate. It is soluble in acetic acid withotit effervescence, and is precipitated in crystalline form from this solution on addition of ammonia. When PHYSIOLOGICAL PROCESS OF URINARY SECRETION. 509 fused, the specimen melts to a white, porcelain-like mass. Basic calcium phos- phate does not effervesce with acids. The solution in hydrochloric acid is pre- cipitated by ammonia. The solution in acetic acid yields calcium oxalate on addition of ammonium oxalate. In order to isolate calcium and magnesium from such stones, the process described in paragraph (a) should be followed. (e) Neutral calcium phosphate is rarely found in calculi, but, on the other hand, not rarely in urinary sand. Such concretions resemble the earthy phos- phates in physical and chemical properties, except that they contain no magnesia. THE PHYSIOLOGICAL PROCESS OF URINARY SECRETION. The two older and most important theories of secretion will be mentioned: (i) Bowman held that the glomeruli secrete only water, and that the epithelial cells of the urinary tubules through their glandu- lar activity furnish the specific urinary elements, which the onflowing urinary water washes out of the cells. (2) C. Ludwig assumed that a dilute urine is secreted in the capsules. Passing through the urinary tubules, this, by endosmosis, returns water to the blood, which is more deficient therein, and to the lymph of the kidney, and thus becomes reduced to normal consistence. The secretion of the urine in the kidneys depends, however, not alone upon physically definable influences, but it must rather, in accordance with a series of acquired facts, be assumed that in addition the vital activity of special secretory cells plays a prominent role. The physical or chemical forces obviously underlying the latter have not as yet been determined. The secretion includes (i) the urinary water, and (2) the urinary elements dissolved therein. Both together constitute the totality of the secretion. The amount of urinary water secreted in the glomeruli determines principally the amount of urine, while the amount of substances dissolved in the urinary water determines the concen- tration of the urine. The amount of urinary water, which is secreted principally in the capsules, depends, in the first place, upon the blood-pressure in the distribution of the renal artery; and, accordingly, is governed by the laws of filtration. The amount of urinary water furnished is, however, not dependent upon the hydrostatic pressure alone, but the functional activity of the cells lining the glomerulus is also of influence. In ad- dition to the water, a certain amount of the salts occurring in the urine is secreted in the glomerulus; albumin, however, is retained. In consideration of the functional activity of the cells, the amount of urinary water must depend also in part upon the rapidity with which new blood conveying the material for secretion passes to the glomeruli; and, in part, upon the amount of urinary elements and water contained in the blood. The independent activity of the secretory cells is present only when their vitality is intact. It is paralyzed in consequence of transitory occlusion of the renal artery. For this reason, the kidney no longer secretes under such circum- stances, even when the circulation is restored after removal of the compression. The observation that the urine is not rarely found to have a higher temperature than the arterial blood is also indicative of this activity. The dependence of the secretion upon the blood-pressure will be made clear by the following observations : i. Increase of the total contents of the vessels, in consequence of which the tension in the -vascular system must increase, increases the 510 PHYSIOLOGICAL PROCESS OF URINARY SECRETION. amount of filtered urinary water. Injections of water directly into the vessels, or the ingestion of considerable quantities of fluid, operates in this direction. If the increase in blood-pressure exceeds a certain level, albumin may even pass into the urine. Conversely, loss of water in consequence of profuse sweating or diarrhea, or copious venesection, as well as prolonged thirst, will cause diminution in the amount of urinary secretion. The circumstance that the blood-pressure does not rise constantly after free drinking is evidence of the functional activity of the cells of the glomeruli, as is also the fact that the amount, of urine is not increased after large transfusions. 2. Diminution in the vascular capacity will operate in a similar manner: contraction of the cutaneous vessels under the influence of cold, stimulation of the vasomotor center or of considerable areas of the vasomotor nerves, ligation or compression of arteries of large size, envelopment of the extremities in tight bandages. Naturally the op- posite conditions will be followed by a reduction in the amount of urine : the influence of heat upon the skin to the point of redness and dila- tation of the vessels, enfeeblement of the stimulation of the vasomotor center, or paralysis of considerable areas of the vasomotor nerves. 3. Increased cardiac activity, in consequence of which the tension and the rapidity of the current in the arterial distribution are increased, augment the amount of urine. Conversely, enfeeblement of the heart's action (paresis of the motor nerves of the heart, disease of the heart- muscle, valvular lesions) diminishes the amount of urine. Artificial irritation of the vagi, in consequence of which, with slowing of the heart- beats, the average blood-pressure fell in animals from 130 to 100 mm. of mercury, with slowing of the pulse, was followed by a reduction in the amount of urine to about one-fifth. At 40 mm. of aortic pressure the secretion of urine ceases. 4. The amount of urine secreted rises or falls with increasing or diminishing fulness of the renal artery. Even moderate compression of the artery in animals is followed by distinct reduction. Pathological. In the presence of fever, there is diminished fulness of the renal vessels, with consecutive reduction in the amount of urine. The observation is of especial significance for the pathogenesis of certain diseases of the kidney that ligature of the renal artery, even if continued for only two hours, causes necrosis of the epithelium of the urinary tubules. In case of arterial anemia of longer duration, necrosis of the entire renal structure takes place. Ribbert found the epithelial cells of the convoluted tubules greatly altered after compression of the renal artery for some time. Most diuretic medicaments act in one or another of the directions indicated. In case of increased diuresis, the lumen of the urinary tubules is increased. The pressure within each afferent vessel must be relatively large, because (i) the duplicate capillary arrangement in the kidney offers considerable resistance, and because (2) the efferent vessel has a much narrower lumen than the afferent vessel. In accordance with these facts, an excretion from the blood into the capsules of the urinary tubules will take place from the capillary loops of the glomerulus in consequence of the filtration-pressure. Dilatation of the afferent vessels, as, for instance, from the action of the nerves upon the unstriated muscular fibers, will increase the filtration-pressure; while constriction will diminish the secretion. If the reduction in the pressure has become so considerable that the blood-current in the renal vein is distinctly slowed, the secretion of urine begins to diminish. It is a remarkable fact that occlusion of the renal veins completely suppresses the secretion. C. Ludwig has concluded from this that the secretion PHYSIOLOGICAL PROCESS OF URINARY SECRETION 511 of fluid accordingly can not take place from the true renal capillaries, because the blood-pressure in these must be increased by occlusion of the veins, and this would cause increased nitration. On the other hand, the observation mentioned would indicate that the secretion takes place from the capillaries of the glomerulus. The venous stasis in the efferent vessel distends this vessel, which arises in the center of the convolution, to such a degree that the capillary loops are pushed together against the wall of the capsule and compressed, so that no nitration can take place from them. Whether some fluid is given off through the urinary tubules, especially the convoluted tubules, is as yet undecided. The amount of urine and the amount of contained urea are diminished by venous stasis in the kidneys. The amount of sodium chlorid remains constant, while that of albumin in pathological urine increases. As the blood-pressure in the renal artery equals between 120 and 140 mm. of mercury, and the urine in the ureter is propelled under exceedingly slight pressure, so that it is no longer capable of escaping against a counter-pressure of from 10 to 40 mm. provided by a manome- ter introduced into the ureter divided transversely it must be clear that the blood-pressure is also capable, as a vis a tergo, of forcing the stream of urine through the ureter. The degree of concentration of the urine depends upon the amount of the constituents in solution passing out of the blood into the urinary water. The cells of the convoluted urinary tubules appear to take up these substances from the blood by means of an independent activity. The urinary water passing through the urinary tubules from the glomerulus, and containing only readily diffusible salts, later takes up these substances out of the cells of the convoluted tubules by a pro- cess of extraction. The independent activity of the cells is indicated by the following facts : i. Sulphindigotate of sodium (indigocarmin), which, when injected into the blood, passes into the urine, can be recognized in the interior of the cells of the urinary tubules, but not in the capsules. Further on, this substance is visible in the lumen of the urinary tubules, whither it is washed by the current of urinary water from the glomerulus. If, in such an experiment, the cortical layer containing the capsules has been removed two days previously by cauterization or with the knife, the blue pigment will have remained in the convoluted tubules. It will not have advanced onward, as the current of water from the de- stroyed glomeruli is wanting. This observation thus indicates that the glomeruli furnish principally the urinary water, and the convoluted tubules the specific urinary elements. Heidenhain and Sauer observed also urates (injected into the blood) secreted by the convoluted tubules. Nussbaum has also demonstrated that urea is not secreted by the cap- sules, but by the urinary tubules. Mobius found the same with respect to the biliary pigment, Glaevecke with respect to the iron salts of the vegetable acids when injected subcutaneously, and Landois first described the same condition with respect to hemoglobin. After in- fusion of milk into the vessels, Landois encountered numerous fat- globules within the cells of the urinary tubules. It appears that the capsules may also take part in the process only after abundant secretion. After infusion of large amounts of sodium sulphindigotate and after the observation has been continued for some time, the epithelium of the Malpighian capsules also exhibits the blue discoloration. Likewise in the presence of albuminuria, the abnormal elimination of albumin takes place first in the urinary tubules and later in the capsules. Also hemoglobin occurs in part in the capsules. Egg-albumin is believed by Nussbaum to be excreted through the capsules. 512 PHYSIOLOGICAL PROCESS OF URINARY SECRETION. Disse studied the alterations in the secretory cells during their activity. With the commencement of this activity the cells become larger, and bright areas of the protoplasm, infiltrated with secretion, appear as halos about the nucleus. The discharge of the secretion into the lumen of the tubules takes place through filtration. The brush- border indicates only the empty cell ; it disappears while the cell is being filled with secretion. Henle, H. Meckel, Leydig, and Bial observed in snails constituents of the urine (guanin) within the cells of the kidney. 2. Also when, either after ligation of the ureter or in consequence of marked reduction in blood-pressure in the renal artery (after division of the cervical cord or venesection), urinary water is no longer secreted, the substances named are, nevertheless, after introduction into the blood, seen to pass over into the urinary tubules. Injection of urea likewise again stimulates the secretion. This indicates that the secre- tory activity takes place independently of the filtration-pressure. The independent vital activity of the glandular cells of the urinary tubules not explainable by physical processes makes it impossible to consider the glandular tubules as a simple apparatus resembling physical membranes. This is shown also by the following experiment: Abeles permitted the circulation of arterial blood to continue artificially through fresh, living, extirpated kidneys. Pale urinous fluid escaped from the ureter drop by drop. If urea or sugar were added to the circulating blood, the vessels became dilated and the secretion contained the admixed substances in greater concentration. Thus, also the surviving kid- ney excretes, in concentrated form, substances that circulate in the blood in a dilute state. The same observation was made by I. Munk in analogous experi- ments with sodium chlorid, potassium nitrate, caffein, grape-sugar, and glycerin, with an increase in the total amount of the secretion. Addition of caffein or theobromin to the circulating blood induces an increase in the secretion, stimu- lates, thus, the secretory cells themselves to increased activity. The assumption of vital activity alone explains, also, why the serum-albumin of the blood does not pass into the urine, although egg- albumin or dissolved hemoglobin, intro- duced into the blood, does so rapidly. Among the salts that occur in the total blood, also in the blood-corpuscles, naturally only those in solution can pass over into the urine. Those that are united to proteids or in the cellular elements cannot pass over, or at least only after decomposition. This fact explains the difference between the salts of the total blood and those of the urine. The urine can, likewise, take up only the gases absorbed into the blood; and not those in chemical combination. Should stagnation of the secretion take place in the ureter, as after ligation, and, later, in the urinary tubules, a return of the secretion into the tissue of the kidney and, later, into the blood will be observed. The kidney becomes edem- atous, in consequence of distention of its lymph-spaces. The secretion is altered, inasmuch as, first, water is reabsorbed into the blood; then the sodium chlorid in secretion is diminished, likewise sulphuric acid and phosphoric acid, and, finally, also the urea. Kreatinin will still be present in considerable amount. A true secretion of urine, later on, no longer takes place. The circumstance, further, is noteworthy that the two kidneys never secrete symmetrically. The condition is one of alternation in activity and hyperemia. The one kidney secretes a fluid containing a larger amount of water, and, at the same time, more sodium chlorid and urea. It may even be more acid. v. Wittich observed that the excretion of uric acid in the kidneys of birds does not take place uniformly in all of the urinary tubules, but only in varying areas. The extirpation of one kidney or its morbid destruction in human beings does not diminish the secretion. There occurs increased activity, with enlargement of the remaining organ; and this is due to the increased functional demands upon the secretory cells of this kidney. THE PREPARATION OF THE URINE. 513 THE PREPARATION OF THE URINE. The question has often been raised, whether the urine is really se- creted through the kidney, or whether the urinary constituents are not in part prepared by the kidney itself. The following experiments will shed light upon this subject: 1. The blood already contains one part of urea in from 3000 to 5000 parts ; but the blood in the renal vein contains less urea than that of the artery. This fact indicates that urea is excreted from the blood. 2. After extirpation of the kidney nephrectomy or ligation of its vessels, urea accumulates in the blood and progressively with the lapse of time to between ^-g- and -g-J-g-. At the same time, fluids containing urea and ammonia are vomited and discharged with the stools. Ani- mals die after such profound operations, moreover, within from one to three days. 3. If the ureters are ligated, the actual secretion of the kidneys soon ceases. After this, the accumulation of urea in the blood likewise in- creases, and, indeed, as it appears, not in greater amount than after nephrectomy. Nevertheless, it is possible that the kidney, in its meta- bolic activity, does, like other portions of the body, prepare some urea in its tissues. 4. The blood of birds contains uric acid even under normal con- ditions. Ligation of the ureters, as well as of the renal vessels, or gradual destruction of the secreting renal epithelium by means of subcutaneous injections of neutral potassium chromate, is followed in birds by a deposition of uric acid in the joints and tissues; so that the serous membranes particularly acquire a whitish incrustation there- from. The brain remains free. Also acid combinations of uric acid with ammonia, sodium, and magnesium are thus deposited. Extir- pation of the kidneys in serpents gives rise to the same phenomena in lesser degree. From these experiments it may be concluded that the urea, and with it probably most of the organic constituents of the urine, are excreted principally through the kidneys, but are not prepared in them. The seat for the formation of all of these substances is probably to be re- ferred to the tissues. The urea is formed from decomposed proteid, and principally in the liver. As a result of experiments with birds and serpents, v. Schroder and Colasanti come to the conclusion that the formation of uric acid cannot be assumed to take place exclusively in any definite organ. Urobilin is formed from hemoglobin. Little is known concerning the physiological-chemical processes in the kidneys themselves. Hippuric acid is formed in part in the kidney, for the blood of herbivora contains no trace thereof; but the synthesis of this substance in rabbits takes place also in other tissues. If blood to which sodium benzoate and glycin have been added is passed through the vessels of a fresh kidney, hippuric acid is formed. If, further, phenol and pyrocatechin are digested with fresh renal tissue, the corresponding sulphuric-acid combinations that occur in the urine are formed. The latter, it is true, are formed also by similar digestion with hepatic and pancreatic tissue and with muscle. From these observations it may be con- cluded that in the body the substances in question are prepared w'ithin the kidneys and the organs named. The kidneys are extremely rich in water, and they yield an alkaline reaction. In addition to serum-albumin, globulin, iiucleo-albumin, albumin soluble in sodium carbonate, a gelatin-yielding substance, fat in the epithelial cells (principally after 33 514 PASSAGE OF VARIOUS SUBSTANCES INTO THE URINE. the ingestion of milk and meat) , the elastic sarcolemma-like substance of the membrana propria of the urinary tubules, and the tissue-elements of the vessels and their unstriated muscles, the kidneys contain leucin, xanthin, hypoxanthin, kreatin, taurin, inosite, cystin (the last is present in no other tissue) ; and of these, the majority pass into the urine either not at all or only in small amount. The presence of these substances indicates, probably, active metabolism in the kidneys; and this is suggested also by the great vessels of the kidney. During the secretion of the kidneys, the blood of the renal vein is said to become bright red, and to be deprived of its fibrin. If alkaline blood-serum be filtered through a layer of nucleo-albumin or lecithin-albumin, an acid filtrate passes through. Liebermann explains in a similar manner the development of acid urine on passing blood- plasma through the renal epithelium containing lecithin-albumin. THE PASSAGE OF VARIOUS SUBSTANCES INTO THE URINE. The following substances pass unchanged into the urine: Alkaline sulphates, borates, silicates, nitrates, carbonates; alkaline chlorids, bromids, and iodids; potassium sulphocyanate, potassium ferrocyanid; salts of the biliary acids; urea, kreatinin; cumaric, oxalic, camphoric, pyrogallic, sebacylic acids; further, many alkaloids, as, for instance, morphin, strychnin, curarin, quinin, caffein; among the pigments, sodium sulphindigotate, carmine, gamboge, madder, logwood, the color- ing-matter of huckleberries, mulberries, cherries, rhubarb; further, santonin; and, finally, the salts of gold, silver, mercury, arsenic, bismuth, antimony, iron (but no lead) , which, however, pass in largest amount into the bile and into the feces. Inorganic acids appear in human beings and carnivora as neutral ammo- nium-salts; in herbivora, as neutral alkaline salts. Certain substances that generally undergo decomposition, even when they gain entrance into the blood in small amounts, pass in part into the urine when they accumulate in the blood in considerable amount, because they are not com- pletely decomposed, such as sugar, hemoglobin, egg- albumin, alkaline salts of the vegetable acids, alcohol, chloroform. Many substances appear in the urine as oxidation-products: moderate amounts of alkaline salts of the vegetable acids as alkaline carbonates; uric acid in part as allantoin; sodium sulphite acid and hyposulphite in part as sodium sulphate; potassium sulphid as potassium sulphate. Many oxids appear as sub- oxids, benzol as phenol. Those bodies, such as glycerin and the resins, that are completely con- sumed, exhibit no special derivatives in the urine. Some substances undergo synthesis with metabolic products, and appear in the urine as conjugated combinations. In this category belongs the develop- ment of hippuric acid by conjugation, the formation of the conjugate sulphates, as well as the formation of urea by synthesis from carbamic acid and ammonia. After administration of camphor, or of chloral and butyl-chloral, a conjugated combination with glycuronic acid, an acid closely allied to sugar, appears in the urine. Taurin and sarcosin undergo conjugation with sulphamic or carbamic acid. Phenyl bromid, when administered, enters into conjugation with mercapturic acid, a body allied to cystin. Tannic acid, C 14 H 10 O 9 , takes up water, and is thus decomposed by hydro- lysis into two molecules of gallic acid 2C 7 H 6 O 5 . Potassium iodate and bromate are reduced to potassium iodid and bromid; malic acid, C 4 H 6 O 5 , in part to succinic acid, C 4 H 6 O 4 ; indigo-blue, C 16 Hi N 2 O 2 , takes up hydrogen to form indigo-white, C 16 H 12 N 2 O 2 . Finally, many substances do not pass into the urine at all, such as serum- albumin, oils, insoluble metallic salts, and metals. INFLUENCE OF THE NERVES UPON THE SECRETION OF THE KIDNEYS. As yet, only the influence of the vasomotor nerves upon the ni- tration of the urine from the renal vessels is known, and these nerves appear to be derived from both halves of the spinal cord for each kidney. In general, it should be borne in mind that dilatation of the branches of INFLUENCE OF NERVES UPON SECRETION OF KIDNEY. 515 the renal arteries, particularly of the afferent vessels, must increase the pressure in the glomeruli, and therefore the amount of filtered fluid increases. The greater the measure in which the dilatation of the vessels is confined to the distribution of the renal artery alone, the greater will be the amount of urine. The lower dorsal nerves, in the dog principally the twelfth and thirteenth, contain the largest number of the vasomotor fibers for the kidney. Division of the renal plexus is, as a rule, followed by increase in the amount of urine. Occasionally, in consequence of the increased pres- sure, albumin is observed to pass into the Malpighian capsules; and with rupture of the vessels of the glomeruli even blood may appear in the urine. The center for these renal vasomotor fibers is situated on the floor of the fourth ventricle, in front of the origin of the vagus. In- jury, as by puncture, in this situation is, therefore, followed by increase in the amount of urine (diabetes insipidus), occasionally with the simul- taneous appearance of albumin and blood. Naturally, any injury of the active nerve-path from the center to the kidney has a similar effect. The center for the vasomotor nerves of the liver is situated close to this center, and injury of the former gives rise to the production of sugar in the liver. Eckhard observed hydruria develop after irritation of the vermiform process of the cerebellum lying upon the medulla. A similar result is brought about in human beings also as a result of irrita- tion in this situation by tumors, inflammatory processes, and the like. If, in addition to the distribution of the renal artery, an adjacent extensive vascular area be paralyzed simultaneously, the blood-pressure in the distribution of the renal artery will be less high; as, at the same time, much blood finds its way into the other paralyzed area. Under such conditions, therefore, either a slight or only a transitory polyuria will be observed. In this way, there results a moderate increase in the amount of urine for a few hours after division of the splanchnic nerve, which contains the vasomotor fibers for the kidney. These leave the spinal cord in part through the first dorsal nerve, and pass into the sympathetic nerve. The splanchnic contains, at the same time, also the fibers for the extensive distribution of the intestinal vessels. Irritation of this nerve is, naturally, attended with the op- posite effect. If, with paralysis of the renal nerves, the overwhelming majority of all of the vasomotors of the body are at once paralyzed, the pressure throughout the entire arterial distribution falls in accordance with the extensive dilatation of all of these vascular paths. In consequence, the secretion of urine diminishes, even to the point of complete cessation. This last effect is seen after division of the cervical cord down to the seventh cervical vertebra. This fact explains the observation that the polyuria that occurs after injury to the floor of the fourth ventricle dis- appears as soon as the spinal cord down to the twelfth dorsal nerve is divided. The presence of a large amount of urea in the blood causes con- traction of the vessels of the body, but dilatation of the renal vessels. Contraction of the vessels, and, therefore, at the same time of the volume of the kidney, are caused by asphyxia and strychnin-poisoning; also irritation of sensory nerves has a similar reflex effect. Extirpation of the nerves of the kidney has the opposite effect. During fever, the vessels of the kidney are contracted, probably in consequence of irritation of the center by the abnormally heated blood. 5i 6 UREMIA; AMMOXIEMIA; URIC-ACID DYSCRASIA. Repeated inhalation of carbon monoxid is said occasionally to be attended with polyuria, perhaps in consequence of paralysis of the center for the vasomotor nerves of the kidneys. According to Cl. Bernard, irritation of the vagus at the cardia causes increased secretion of urine, with reddening of the blood in the renal veins. Possibly this nerve contains vasodilator fibers that behave similarly to the corresponding fibers in the facial nerve for the salivary glands. The vagus innervates the intrinsic unstriated musculature of the kidney. According to Arthaud and Butte and others, irritation of a peripheral ex- tremity of the vagus, conversely, diminishes the secretion of urine and the circu- lation in both kidneys. Atropin renders the experiment impossible. The vagus thus appears to be the vasomotor nerve of the kidney. According to Boeri, it possesses trophic functions, as albuminuria occurs after division of the vagus. Irritation of the cervical sympathetic likewise diminishes the secretion. This irritation appears to be reflex, being transmitted through the spinal cord to the splanchnic nerve. UREMIA; AMMONIEMIA; URIC-ACID DYSCRASIA. After extirpation of the kidneys, nephrectomy, or ligation of the ureters, which renders further secretion of urine impossible; further, also, in human beings, as a result of extreme urinary stasis, as well as in consequence of morbid alterations in the kidneys (inflammation, fatty degeneration, and desquamation of the epithe- lial cells of the urinary tubules, cicatricial contraction of the kidney, amyloid degeneration) , there develop a series of characteristic phenomena that resemble an intoxication, and, if of marked degree, cause death, with degeneration of the ganglia in the cerebral cortex and the spinal cord. This condition is designated uremic intoxication or uremia. Among the phenomena, the following are con- spicuous: Mental prostration, somnolence, even loss of consciousness to the point of deep coma, and, in addition, from time to time, the occurrence of twitching or even widespread, severe convulsions. Occasionally, there are delirium and feneral excitement. At the same time, the occurrence of the so-called Cheyne- tokes respiratory phenomenon is often observed. Occasionally, transitory^ in- variably bilateral, blindness occurs, from toxic paralysis of the psycho-optic center. There may, however, take place, quite independently, hemorrhagic extravasations into the retina, causing, rarely permanent, blindness apoplectic retinitis. Also impairment of hearing is observed. Vomiting and diarrhea are common. Ammonium carbonate, formed in the digestive tract from urea, as well as kreatin, causes uremip diarrhea. Also the breath and the emanation from the skin may exhale the odor of ammonia. The alkalinity of the blood and the amount of oxygen in the blood are diminished. The retention of substances that are normally excreted by the urine must be considered as the cause of these symptoms, although it has not, as yet, been possible to designate with certainty the substances that must be considered as the agents upon which the toxic phenomena depend. Suspicion was first directed to urea. v. Voit observed that even healthy dogs exhibited uremic manifestations when they partook of urea for a considerable time with their food if. at the same time, the use of water, which would have carried off the urea rapidly through the kidneys, was prevented. Further, Meissner found that death amid uremic manifestations could be hastened in nephrectomized animals, if urea was at the same time injected into the blood. An injection of moderate amounts of urea into the blood of entirely healthy animals was not, it is true, followed by uremic symptoms, although one or two grams caused a comatose state in rabbits. Dogs died after subcutaneous injection of urea to an amount equaling one per cent, of the bodily weight. Hippuric acid is said to have an entirely similar effect in frogs. Although urea, when introduced into the blood in large amounts, causes death with convulsions, this condition should not be confounded with uremic attacks of intermittent occurrence. As injection of ammonium carbonate causes symptoms similar to those of uremia, v. Frerichs and Stannius believed that the decomposition of urea in the blood causes the intoxication ammoniemia. However, after nephrectomy or ligation of the ureters, even on simultaneous injection of urea into the blood, careful chemical investigation fails to disclose the presence of ammonia in the blood. Therefore, spontaneous formation of ammonia in the blood cannot be the cause of the uremic symptoms. STRUCTURE AND FUNCTIONS OF THE URETERS. 517 As in birds and reptiles, which eliminate principally uric acid, ligation of the ureters likewise induces a comatose state, it was necessary to think of other sub- stances as possibly causing the toxic symptoms. Meissner observed prostration and twitchings develop in dogs after injection of kreatinin. Cl. Bernard, Traube, Ranke, Astaschewsky, Feltz and Ritter, and others attribute the phenomenon to an accumulation of the neutral potassium-salts; Schottin and Oppler suggest the accumulation of normal or abnormally decomposed extractives, Thudichum that of the oxidation-stages of the urinary pigment. Possibly many substances and their decomposition-products act in conjunction. R. Fleischer found a reduc- tion in the elimination of sulphuric and phosphoric acids in advance of the ure- mic attack in man. On placing various substances occurring in the urine kreatinin, kreatin, acid potassium phosphate, uratic sediment from human urine directly upon the sur- face of the cerebrum, Landois observed the development of all signs of uremia. There occurred, particularly, fully developed convulsive seizures, with intervals of rest, in dogs, with subsequent coma. Also, many other secondary phenomena of uremic eclampsia could be thus induced. Urea is inactive in this direction, ammonium carbonate, leucin, sodium carbonate, sodium chlorid, potassium chlorid, feebly active. After long-continued excessive ingestion of food, together with the use of spirit, and slight activity, there occurs, principally in conjunction with respiratory disorders, derangement of metabolism, and not rarely a marked accumulation of uric acid in the blood. The latter is deposited in the joints and their ligaments and cartilages, principally of the foot and the hand, and gives rise to inflammatory and painful attacks gouty nodules, uric arthritis. Rarely, the kidneys, the heart, and the liver are involved. In the vicinity of the foci, the tissues undergo necrosis. Food containing nuclein is to be avoided; also meat-broths, meat- extract, sodium chlorid; while cheese, peptone, legumins, and aleuronat are to be commended. As to the amins, piperazin, lysidin, v lycetol, urotropin, the in- vestigations are not as yet concluded. As uric acid is more readily soluble in solutions of urea, the administration of this substance has been advised. Uric acid introduced into the blood or into the lymphatic system causes changes in the renal epithelium, in the form of uric-acid spheroliths between and within the cells of the convoluted tubules. Administration of adenin, while it does not increase the excretion of uric acid, favors its deposition in the kidney amid in- flammatory symptoms. In birds, long-continued administration of oxalates, sugar, acetone, phenol, gives rise to deposition of urates in the urinary tubules, as well as in the serous and the synovial membranes, and these have disappeared after administration of piperazin. Human urine, when injected beneath the skin or into the veins of animals, has a toxic and even fatal effect, particularly in the case of infectious diseases, diseases of the liver, carcinoma, exophthalmic goiter, and, in accordance herewith, after extirpation of the thyroid gland. The toxic properties are due to organic (toxins) and inorganic constituents, principally potassium-salts. Pregnant ani- mals are especially susceptible to this poison. STRUCTURE AND FUNCTIONS OF THE URETERS. The pelvis of the kidney and the ureter possess a mucous membrane con- stituted of delicate connective-tissue fibers with many embedded cells, upon which a laminated transitional epithelium is situated. The deepest layer of the latter is provided with small, round, soft cells. Then follows a layer of more nearly vertical, club-shaped and bulbous colls, whose attenuated extremities ramify between the cells of the deepest layer; the free surface is covered by cubical cells, which finally are surmounted by a homogeneous cuticular border. Beneath the epithelium there is a layer of adenoid tissue, containing disseminated lymph- follicles. In the pelvis of the kidney, the mucous membrane contains isolated small grape-like mucous glands, which are present also in the ureter. The muscular coat consists of an internal somewhat thicker longitudinal layer and an external circular layer, to which, in its lower third, a number of disseminated bundles of longitudinal fibers are added. All of these layers are rather freely interwoven with connective tissue. The external connective-tissue sheath forms a sort of adventitia, in which the larger vessels and the nerves, together with the ganglia, are situated. The layers of the ureter may be followed upward to the pelvis of the kidney and to the calices. They finally line the pelvis itself only with mucous STRUCTURE AND FUNCTIONS OF THE URETERS. membrane, passing over upon the base of the pyramids, while the muscle-fibers cease at the foot of the pyramids, where they form a sort of sphincter about the pyramids by means of circular bundles. The blood-vessels supply the various layers and form a capillary network beneath the epithelium. The relatively scanty medullated nerves, in the vicinity of which ganglia are found, in part supply the muscles as motor fibers, while in part they penetrate toward the epithe- lium. These are reflex and sensory, as indicated by the severe pain attending impaction of calculi. The ureter penetrates the thickness of the bladder- wall, passing obliquely through it for a considerable distance. The internal opening is a slit in the mucous membrane directed obliquely inward and downward, and provided with a sharp, valve-like process (Fig. 177) . The propulsion of the urine through the ureter takes place (i) in consequence of the fact that the urine constantly secreted in the kidney under considerable pressure forces on- ward the urine in the ureter, which is under lower pressure. (2) In the erect posture, the urine flows by gravity d own the ureter . ( 3 ) The muscles of the ureter through their peristaltic movement propel the urine into the bladder. This movement occurs on- ly as a reflex phenom- enon in response to the entrance of the urine, a few drops every three-quarters of a minute, or in con- FIG. 177. Lower Portion of the Male Bladder, with the Commencement of the Ureter, Opened through a Median Incision in the Anterior Wall, and spread out (after Henle). The clear lines of the trigone, the slit- like openings of the ureters, the ureters divided above and the seminal vesicles can be recognized. On the colliculus seminalis there appear in the middle the large opening of the prostatic sinus, and on either side the small circular orifice of the ejaculatory duct, and below both the numerous punctate openings of the excretory ducts of the prostate gland. sequence of direct ir- ritation. It always passes downward with a velocity of from 20 to 30 mm. in a second. The greater the distention of the ureter by the urine, the more rapidly does this peristaltic movement take place. Asphyxia, venous hyperemia, and irritation of the splanchnic increase the number of contractions; while rapid ligation of the renal vessels, as well as ligation of the ureter, diminishes them. In case of local irritation, the contraction takes place in both directions. As Engelmann observed these movements also in excised portions of ureter in which neither nerve-fibers nor ganglia were visible, he believes that the move- ments are due to direct muscular conduction in the unstriated muscles, just as takes place in the heart. The stagnation of urine toward the kidney is prevented (i) by the fact that the secretion collecting in the pelvis of the kidney and in the calices under high pressure presses upon the pyramids from all sides, so that the urine cannot pass back into the urinary tubules closed by pres- sure. (2) If when the urine has accumulated in the ureter in consid- erable amount, as from occlusion by concretions, the musculature en- STRUCTURE OF URINARY BLADDER AND URETHRA. 519 gages in increased activity for the propulsion of the urine, the portion of the muscular fibers surrounding the pyramids so compresses the urinary tubules that the urine cannot pass back into the excretory ducts of the tubules. The return of urine from the bladder into the ureter is ren- dered difficult in part by the fact that with marked stretching of the bladder-wall the ureter, in so far as it is contained therein, is likewise com- pressed ; and in part by the fact that the stretching of the mucous mem- brane of the bladder firmly approximates the margins of the slit -like openings of the ureters (Fig. 177). In case of retention of urine in the bladder, a return of urine into the ureters may, it is true, take place. STRUCTURE OF THE URINARY BLADDER AND THE URETHRA. The mucous membrane of the bladder is not unlike that of the ureter. The laminated epithelium exhibits flatter cells in the upper layer. When the bladder is distended, the epithelial cells become stretched and thinner. The unstriated muscular fibers are arranged in bundles that form an external longitudinal layer and an internal circular layer. In addition, fibers pass in various directions and cross one another, forming a wide-meshed trabecular network. Between the mus- cular coat and the mucous membrane there is a layer of delicate, fibrillar, cellular connective tissue, with an intermixture of elastic fibers. An excessively minute dissection of the individual layers and bands of the musculature of the bladder has given rise to erroneous physiological interpretations. In this category belongs the establishment of a special detrusor urinas muscle, which is said to consist of fibers pursuing a vertical direction from the vertex to the fundus, principally upon the anterior and posterior surfaces. The conception of a special internal sphincter vesicse is likewise unjustified as constituted of a circular layer of un- striped muscles, from 6 to 12 mm. thick, surrounding the commencement of the urethra, and in its form helping to give rise to the funnel-shape of the outlet of the bladder. This layer, also designated annulus urethralis vesicae, is no sphincter at all. In the trigone of Lieutaud there are, at times, between the orifices of the ureters, numerous muscular bundles, attached in part to the circular, in part to the longitudinal fibers of the wall of the bladder. Waldeyer believes, par- ticularly of the trigone, that it facilitates the distention of the bladder, favors its complete evacuation and aids its closure. From the physiological standpoint, it should be borne in mind that the entire musculature of the bladder represents a continuous hollow muscle whose sole function it is, in contracting, to diminish the cavity of the bladder from all directions and to expel its contents. The vessels of the bladder resemble those of the ureter in their distribution. The nerve-fibers are provided with ganglia, as is the case generally at all parts of the urinary passages outside the kidney. These are situated in part in the mucosa, in part in the muscularis, and they communicate with one another by means of filaments. In the mucous membrane and its epithelium, the nerves terminate in end-bulbs. In accordance with their functions, the nerves are motor, sensory, reflex, and vascular. In women, the urethra serves only as the excretory duct of the urinary bladder. The mucous membrane, formed of a large amount of fibrillary con- nective and elastic tissue and supplied with papillae, is lined by laminated pavement epithelium. In addition, a number of Littre's mucous glands are embedded in it. Next to the mucous membrane is a layer of longitudinal unstriated muscular fibers, and next to the latter a layer of circular fibers. These layers contain an abundance of connective-tissue and elastic fibers, and, besides, extensive venous plexuses, suggestive in their structure of cavernous spaces. The true sphincter muscle of the bladder is a striated muscle, which undergoes contraction and relaxation under the influence of the will, and consists in part of transverse, completely circular fibers, which extend 520 EVACUATION OF THE URINE. downward to the middle of the urethra and lie next to the unstriated cir- cular fibers, and in part of longitudinal fibers, which pass upward to the base of the bladder only on the posterior wall of the urethra, and down- ward between the circular fibers. Additional circular fibers are situated below the middle of the urethra, and only in isolated distribution on its anterior surface. In the male urethra, the epithelium of the prostatic portion still resembles that of the bladder, in the membranous portion it becomes laminated, and in the cavernous portion a simple cylindrical epithelium. The mucous membrane beneath the laminated epithelium, provided with papillae, contains, principally in the posterior portion, the mucus-secreting glands of Littre. Unstriated muscle- fibers are present in the prostatic portion as a longitudinal layer, especially at the colliculus seminalis; while the membranous portion contains principally cir- cular fibers, with intervening longitudinal fibers. The cavernous portion contains posteriorly delicate circular fibers, anteriorly only isolated insignificant oblique and longitudinal fibers. With respect to the mechanism for closure of the male urethra, it should be pointed out that the so-called internal sphincter vesicse of the anatomists, which consists of unstriated muscular fibers, and, as an integ- ral portion of the musculature of the bladder surrounds the commencement of the urethra down to within the prostatic portion of the urethra, above the colliculus seminalis, is not a sphincter muscle at all. The true striated sphincter of the urethra, or external sphincter of the bladder, is situated below the former. It is a completely circular muscle, surround- ing the urethra, just above the entrance of the urethra into the urogen- ital septum, at the apex of the prostate gland, where its fibers anasto- mose with those of the subjacent deep transverse peroneal muscle. This sphincter muscle includes, also, longitudinal fibers, which pass downward from the bladder along the upper border of the prostate. Isolated transverse bundles are derived anteriorly from the surface of the neck of the bladder. The sphincter muscle includes, besides, certain transverse fibers that lie within the prostate even opposite the apex of the colliculus seminalis, passing like a thick transverse column in advance of the commencement of the urethra into the structure of the prostate prostatic muscle. In the male urethra, the blood-vessels form a rich capillary network beneath the epithelium, in the midst of which a wide-meshed lymphatic vascular net- work is situated. COLLECTION AND RETENTION OF THE URINE IN THE BLADDER. EVACUATION OF THE URINE. After the evacuation of the bladder, urine reaccumulates, with grad- ual distention of the viscus. As long as the amount of urine is but mod- erate, the elasticity of the elastic fibers surrounding the urethra and of the sphincter muscle of the urethra in men, in addition, that of the prostate suffices perfectly to retain the urine in the bladder. This is indicated by the fact that in the cadaver the urine does not escape from the bladder. The movements for the evacuation of the bladder, as well as for the retention of the urine in the bladder, exhibit, in many respects, an agreement with the motor mechanism at the rectum. In the first place, it should be pointed out that the walls of the bladder are capable of independent contraction. Whether these are due to the ganglion-cells in the bladder that are found in the course of the nerves has not been demonstrated. It is rather more likely that the muscula- ture of the bladder is capable of rhythmic movement without nervous aid. EVACUATION OF THE URIXE. 521 The urinary bladder, especially when considerably distended, exhibits the occurrence of intermittent slight contractions, which can be compared with the peristaltic movements of the intestines. Even the excised frog's bladder, and even portions thereof without ganglia, exhibit similar rhythmic contractions, which can be increased by heat. After division of all of the nerves of the bladder, bleeding with asphyxia is still followed by contractions as a result of direct stimu- lation of the muscles of the bladder. The contractions occur, further, more actively in the presence of derangement of the circulation in the bladder, or of venosity of the blood, in the same way as the movements of the intestine are brought about in marked degree by like influences. In this category belongs the evacuation of the urine when the action of the heart ceases in cases of sudden asphyxia or protracted suppression of respiration. As emotional disturbances also influence the contraction of the walls of the bladder, the evacuation of the urine in connection with sudden fear can be explained in this manner. In the state of apnea, as well as in apneic intervals after persistent deep respiratory movements, the independent contractions of the bladder cease. In order to comprehend the mechanism of the retention of the urine in the bladder, as well as of its evacuation, a description is necessary of the following nervous apparatus which participates in these processes : T . The sensory nerves of the walls of the bladder are derived from the first, second, third, and fourth posterior sacral roots. A number of sensory fibers pass into the spinal cord through the intermediation of the hypogastric plexus. The sensory nerves pass upward in the cord to the cerebral cortex. 2. The center for reflex stimulation of the unstriated musculature of the wall of the bladder vesicospinal center is situated in the neigh- borhood of the fourth lumbar vertebra, in the dog. 3 . The motor tracts pass from this center to the unstriated muscula- ture of the wall of the bladder through the nerves between the second lumbar by way of communicating branches of the sympathetic and the fourth sacral by way of the nervi erigentes. Irritation of the sensory nerves of the wall of the bladder causes reflex contraction of the bladder-wall. In addition to the sensory nerves of the bladder, the reflex described may be excited also by irritation of other sensory nerves; thus, active tickling, or warming of the region of the knee during sleep at times causes evacuation of urine, likewise the hearing of splashing and whistling sounds. In animals, stimulation of certain sensory nerves likewise causes contractions of the bladder. Omitting consideration of the sphincter muscle of the urethra, the sensation of a distended bladder will become apparent as soon as the bladder is moderately distended. Then the mechanical irritation of the sensory nerves of the bladder in the mucous membrane excites in* the vesicospinal center the reflex through the motor nerves of the unstriated musculature of the bladder, and in consequence of this the walls of the bladder undergo contraction . This constitutes the process as it takes place , for instance, normally always in infants, who do not as yet have control of the urethral sphincter. Also voluntary evacuation of the bladder, whatever the degree of distention, is always effected only through exci- tation of the reflex described. The will is incapable of influencing di- rectly the unstriated musculature of the bladder ; and this is emphasized particularly by the author, in opposition to the statements of many other observers. To induce reflex stimulation of this movement of the bladder, principally in the presence of considerable degrees of distention, the direction of the attention to the sensations in the urinary apparatus 522 EVACUATION OF THE URINE. alone suffices. When the distention of the bladder is only moderate or slight, the sensory, excito-reflex nerves of the bladder must first be stimu- lated, and either through irritation of the sensory nerves by voluntary contraction of the striated muscles of the urethra and the floor of the pelvis, or of the nerves of the bladder as a result of abdominal pressure. As electric stimulation from the cerebral peduncle downward through the motor paths of the spinal cord to the motor nerves of the unstriated musculature of the bladder causes contraction of the bladder, many investigators have concluded that the will is capable of exciting spon- taneous contractions of the bladder directly in this way. The author con- siders this view as incorrect. In his opinion, voluntary evacuation of urine is always induced by reflex influences, in the excitation of which the will participates only in a secondary manner. With the vesical center situated in the spinal cord still other nervous apparatus cooper- ates. As painful irritation of sensory nerves in different parts of the body also is capable of causing reflex contraction of the bladder the involuntary discharge of urine that occurs frequently in children suffer- ing from disorders of dentition may be of this character; as, further, as has already been pointed out, sensory nerves situated at a higher level, even cerebral nerves, are capable of exciting the vesical reflex, it must be concluded that the vesical center extends for a considerable distance up- ward, perhaps to the anterior portion of the optic thalamus, and that from these higher levels descend motor paths that are susceptible of possibly reflex stimulation in the spinal cord. Irritation of the medulla from the cerebral peduncle downward causes contraction of the walls of the bladder. With respect to the mechanism for the retention of the urine in the bladder through the sphincter muscle of the urethra, consideration should be given to the following facts : 4. The motor nerves for the striated sphincter muscle are con- tained in the pudendal nerve, derived from the anterior roots of the third and fourth sacral nerves. Irritation causes contraction of the muscle; paralysis, inability to close the urethra, with the result that dribbling or incontinence of urine takes place. The nerves maybe both stimulated voluntary interruption of the stream of urine and in- hibited through the action of the will. 5. The sensory nerves of the urethra pass into the spinal cord through the posterior roots of the third, fourth, and fifth sacral nerves. These stimulate, on the one hand, the reflex for the urethral sphincter, so that as soon as urine escapes from the bladder into the commencement of the urethra the sphincter muscle contracts; as, for instance, in adults, during sleep, when the bladder becomes distended. On the other hand, they transmit sensory impressions from the urethra, particularly also when urine forces its way into the canal. 6. The center for the urethral -sphincter reflex urethrospinal cen- ter is situated, in the dog, at the level of the fifth, and, in the rabbit, at the level of the seventh lumbar vertebra. 7. From the cerebral cortex the voluntary motor paths course down- ward through the spinal cord to the sphincter muscle of the urethra, within the pyramidal tracts. 8. The inhibitory paths for this muscle likewise pass from the brain through the spinal cord, and through them the muscle may voluntarily DERANGEMENT OF URINARY RETENTION AND MICTURITION. 523 be relaxed into inactivity. It has not yet been possible to stimulate this center experimentally. With respect to the mutual relations between the activity of the mus- culature of the bladder expulsion of urine and of the sphincter of the urethra retention of urine the action of the sphincter muscle pre- ponderates, as a rule, when the distent ion of the bladder is not excessive. In other words, as soon as urine is forced into the urethra by contraction of the musculature of the bladder, reflex closure of the urethra takes place. The action of the sphincter muscle, however, predominates only to a certain degree; and neither the reflex nor the voluntary con- traction of the sphincter is capable of resisting strong pressure by the urine. In the act of micturition, as it takes place when the bladder is moderately distended, the sphincter of the urethra must always be vol- untarily inhibited in its contraction during the contraction of the walls of the bladder. The foregoing description of the innervational conditions of the bladder is based upon the published experiments of Budge, all of which were performed in collaboration with Landois. Division of the sacral nerves, in the dog, causes degeneration of the nerves of the bladder and of the rectum, but not of the internal genitalia some fibers of the urethral and vulvar nerves undergo degeneration. Bilateral division renders micturition an'd defecation impossible, while unilateral division renders these difficult. In addition, there is complete anesthesia at the anus, of the vagina, and on the posterior aspect of the thigns, together with weak- ness at the ankle-joint. Normally, the bladder is completely evacuated. The residual urine that col- lects abnormally in greater or lesser amount is a source of danger, on account of the tendency to decomposition. The urine undergoes alterations during its sojourn in the bladder. According to Kaupp, retention is attended with an increase in the amount of sodium chlorid, and a diminution in the amount of urea and of water. The reduction in the latter is much more marked in con- junction with simultaneous sweating. The question whether the mucous mem- brane of the bladder absorbs soluble matters has been answered in the affirmative by Cl. Bernard, for the dog. Under such circumstances, water is again excreted into the bladder. Maas and Pinner noted absorption also on the part of the urethral mucous membrane, Lewin and Goldschmidt also on the part of the ureter, and the pelvis of the kidney, as well as the prostatic vesicle (strychnin). As the ureters empty rather toward the base of the bladder, the urine most recently secreted is always the lowermost. Under varying conditions of secretion the urine may therefore (in a resting posture) form layers in the bladder, so that when evacuated the different layers may be clearly distinguishable. In quiet dorsal decubitus, the pressure in the bladder is from 13 to 15 cu. cm. of a column of water. The pressure is naturally increased by increase of the intra-abdominal pressure, especially in consequence of coughing and expulsive efforts. The erect posture has a similar effect, in consequence of the pressure of the viscera from above. In the evacuation of the urine, the amount expelled is at first small; this increases later in the same interval of time, and toward the end of the act it again diminishes. In men, the last portions are expelled from the urethra through voluntary contraction of the bulbo-cavernous muscle. Adult dogs constantly accelerate the stream of urine rhythmically through the action of this muscle. MORBID DERANGEMENT OF URINARY RETENTION AND OF MICTURITION. Derangement in the mechanism of retention and evacuation of urine may be referred by the physician to its cause from a consideration of the physiological conditions described. Retention of urine ischuria results (i) from occlusion of the urethra by foreign bodies, concretions, strictures, prostatic enlargement; (2) from paralysis or exhaustion of the musculature of the bladder, the latter also following parturition in consequence of the pressure of the child's parts against the bladder; (3) primarily, after division of the spinal cord. Under such circum- 524 COMPARATIVE. HISTORICAL. stances, retention of urine takes place (a) because the division of the spinal cord gives rise to increased reflex activity on the part of the urethral sphincter, and (b) because inhibition of this reflex cannot take place. If, with increasing distention of the walls of the bladder, the urethral orifice is finally dilated mechanically, dribbling of urine takes place. Nevertheless, the urine escapes only drop by drop, as it overcomes the maximum tension at which the urethra still closes. Therefore, the bladder becomes more and more distended, as the tone of the continuously stretched walls lessens progressively, and the bladder may be distended to an enormous size. In consequence of the entrance of bacteria into the bladder, ammoniacal decomposition of the long-retained urine may readily take place; and, as a result, catarrhal and inflammatory conditions of the bladder may be excited. (4) From interference with the voluntary control of the inhibition of the reflex of the urethral sphincter, as well as from increased reflex excitability of the urethral center. Incontinence of urine stillicidium urinas occurs as a result (i) of paralysis of the urethral sphincter; (2) of anesthesia of the urethra, in consequence of which the reflex of the sphincter must be lost; (3) incontinence of urine is, sec- ondarily, always a result of division of the spinal cord or of abnormal degeneration. Strangury is observed as an excessive reflex of the walls of the bladder and the sphincter muscle, in consequence of irritation of the bladder and the urethra, as observed in association with inflammation, irritation, and neuralgia. So-called nocturnal enuresis, nocturnal involuntary discharge of urine, may be a result of increased reflex activity of the walls of the bladder, or of enfeeblement of the reflex of the sphincter muscle. Nothing of a definite nature is known as to the influence of deranged action of the will,. principally in connection with unilateral injury, apoplexy, and the like. In patients suffering from disease of the spinal cord, there is impairment of the sensation of a distended bladder, as well as of the contractile power of the walls of the bladder. In neurasthenic patients, the latter is diminished, while the sensation of distention is increased. In patients with prostatic disease, there is, at first, likewise increased sensitivity with a dis- tended bladder. COMPARATIVE. HISTORICAL. In vertebrates, with exception of the bony fishes, there is often a union of the urinary and the generative organs. The primitive kidney (Wolffian body), which serves during the first period of embryonic life as an excretory organ, assumes this function throughout life in fish and amphibia. The myxenoids (cyclostomata) possess the simplest kidneys : On either side there is a long ureter, upon which are situated capsules with short pedicles containing glomeruli, and arranged in rows. Both ureters empty into the genital pore. In the remaining fishes, the kidneys often extend longitudinally, lying as more compact masses on either side of the vertebral column. The two ureters unite to form the urethra, which always opens behind the anus, either united with the genital orifice or behind this. In the sturgeon and the shark the anus and the urethral orifice together form a cloaca. Bladder-like formations, which, however, do not resemble the urinary bladder of mammalia morphologically, occur in fish, either at each ureter (ray, shark) or at the junction of the two. In amphibia, the efferent vessels of the testicles unite with the urinary tubules. The testicular-renal duct unites, in the frog, with that of the other side; and both, united, open into the cloaca, while the capacious urinary bladder opens through the anterior wall of the cloaca. From the reptiles upward, the kidney in all vertebrates is no longer the per- sisting Wolffian body, but a newly formed organ. In reptiles, it is generally flattened longitudinally. The ureters open separately into the cloaca. Saurians and tortoises possess a bladder opening into the anterior wall of the cloaca. In birds, the ureters remain separate and open into the urogenital sinus emptying into the cloaca internally to the excretory ducts of the generative glands. The bladder is constantly wanting. In mammalia, the kidneys often consist of many small lobules, reniculi, as, for instance, in the seal, the dolphin, the ox. Among invertebrate animals, molluscs possess excretory organs in the form of canals provided with an external opening and an internal opening, communi- cating with the cavity of the body, and occasionally functionating also as oviducts. In mussels, this canal is expanded into a spongy organ (organ of Bojanus) , situated at the base of the gills, often possessing a central cavity of considerable size, and FUNCTIONS OF THE EXTERNAL INTEGUMENT. 525 provided with ciliated secretory cells. The internal (ciliated) excretory duct opens into the pericardial cavity; the outer, occasionally united with the sexual orifices, opens upon the external surface of the body. In the analogous, generally un- paired, often contractile organ of snails, guanin has been demonstrated. The organ is capable, in a remarkable manner, not alone of excreting water from the blood, but also of conveying water into the blood. Cephalopods possess sacculated ex- cretory organs, provided with glands and opening into the mantel-cavity lying on the vascular trunks of the gills. Insects, spiders, and centipedes have so-called Malpighian vessels, partly as uric-acid forming excretory organs; partly, also, as biliary organs. These vessels are long tubes that open into the commencement of the large intestine. In crabs, the blind tubes of the digestive tract probably have similar functions. In cestodes, the excretory organs are longitudinal tubes; in tape-worms two that extend throughout the entire chain, in the teniag anastomosing at the junction of the segments by means of a large communication. In trematodes (distomum) the branching organ opens at the posterior extremity of the body. Also in most round-worms the excretory organ is formed of tubes, which, united, open at a pore in the abdominal line. Earth-worms possess, almost in all segments of the body in pairs, the so-called nephridia-canals, that is, tubes, often much con- voluted, that commence in the abdominal cavity with an inner, ciliated orifice, and communicate upon the ventral aspect of the body with the external surface . In the sea-urchin, the star-fish, and the medusae, the water- vascular system is, at the same time, the excretory organ. Also in sponges, the canals passing through the body and conveying water may be considered as such. Historical. According to Aristotle the urine is derived from the blood passing through the kidneys, and then flows through the ureters into the bladder; the venous blood of the kidneys does not undergo coagulation. He pointed out the relatively large size of the human bladder. Berengar (1521) observed, on injecting water into the renal vessels, that fluid escaped from the papilla?. Massa (1552) discovered lymphatic vessels in the kidneys. Eustachius (died 1580) ligated the ureters and subsequently found the bladder empty. Cusanus (1450) studied the color and the specific gravity of the urine. Rousset (1581) pointed out the muscular nature of the walls of the bladder, in which Sanctorius (1631) was un- able to recognize any special sphincter muscle; while Vesling (1641) had already described the trigone of Lieutaud (1753). The first more important chemical investigations were made by van Helmont in 1644. He demonstrated the solid constituents of the urine, and found among them sodium chlorid. He noted the higher specific gravity of febrile urine, and explained the development of urinary calculi from the solid constituents of the urine. With respect to the discovery of individual urinary constituents, it may be noted that Scheele, in 1776, dis- covered uric acid; Bergmann calcium phosphate; Brand and Kunckel phosphorus; Rouelle, in 1773, urea, which was named by Fourcroy and Vauquelin in 1799; Berzelius lactic acid; Seguin albumin in pathological urine; J. v. Liebig hippuric acid; Heintz and v. Pettenkofer kreatin and kreatinin; Wollaston, in 1810, cystin; Marcet, in 1817, xanthin; Lindbergson magnesium carbonate. The more recent histological, physiological, and chemical investigations are discussed in the text. FUNCTIONS OF THE EXTERNAL INTEGUMENT. STRUCTURE OF THE SKIN. The external integument, from 2.3 to 2.7 mm. thick, with a specific gravity of 1057, is constituted of the cults rcni, corium, cutis, and the overlying epidermis. The corium (Fig. 178, I, C) forms upon the entire surface numerous papillae, from o.i to 0.5 mm. high, of which the largest are encountered upon the palmar aspect of the hand and the plantar aspect of the foot, as well as upon the nipple and the glans penis. The majority of the papillae contain loops of capillary blood-vessels (g) , and in circumscribed areas of the skin also so-called tactile corpuscles (Fig. 179, a). The papillae are arranged upon the skin in groups in the small areas bounded by the delicate furrows in the skin that are still macro- scopically visible. On the palmar aspect of the hand and the plantar aspect of the foot they follow the characteristic cutaneous lines. The horny skin consists 5 26 STRUCTURE OF THE SKIN. of a dense, uniformly woven network of elastic fibers, more delicate in the papillae, and coarser in the deeper layers, with which fibrillary connective tissue, with connective-tissue corpuscles and lymphoid cells, are intermixed. In the deepest layers, the connective tissue predominates, and, by the interlacing of its bundles, forms longitudinal-rhombic reticular spaces (a a), generally filled with fatty tissue, whose longitudinal expansion corresponds with that of the greatest degree of FIG. 178. Histology of the Skin and the Epidermoidal Structures: I, transverse section through the skin, with hair and sebaceous glands (T), corium and epidermis are shown in reduced size; i, external, 2, internal fibrous layer of the hair-follicle; 3, cuticula of the hair-follicle; 4, external root-sheath; 5, Henle's layer of the inner root-sheath; 6, Huxley's layer of the inner root-sheath; p, hair-root attached to the vascular hair-papilla; A, arrector pili muscle; C, corium; a, subcutaneous fatty tissue; b, horny layer; d, Malpighian mucous layer of the epidermis; g, vessels of the cutaneous papillae; v, lymphatics of the cutaneous papillae; h, horny substance; i, medullary canal; k, epidermis of the hair; K, sudoriferous gland; E, epidermal scales from the horny layer, viewed partly from the side, partly from the surface; R, prickle-cells from the Malpighian layer; n, superficial, deep nail-cells; H, hair, more highly magnified; e, epidermis; c, medullary canal with medullary cells; f f, fiber cells of the hair-substance; x, cells of Huxley's layer; i, cells of Henle's layer; S, transverse section through a sudoriferous gland of the axillary cavity; a, adjacent unstriated muscular fibers; t, cells of a sebaceous gland, in part with fatty contents. tension of the skin at the part of the body in question. Beneath the corium lies the subcutaneous connective tissue, which, however, is without fat-cells in some places. At certain points, firm fibrous bands of connective tissue unite the skin to the underlying fascia, ligaments, or bones (tenacula cutis). In other situations, principally over projecting bony parts, there are subcutaneous mucous bursae filled with a synovial-like fluid, their interior partly lined by endothelium. THE NAILS AND THE HAIR. 527 Unstriated muscle-fibers are present in the uppermost layers of the corium, principally on the extensor aspects; further, particularly on the nipple, the mam- millary areola, the prepuce, the perineum, and in especial abundance in the tunica dartos of the scrotum. The arteries of the skin in the palm of the hand and the sole of the foot, which must sustain the greatest amount of pressure, possess the thickest walls for the propulsion of the blood-stream. In silver- workers, the elastic fibers of the skin of the hands are discolored black in places from the deposition of reduced silver, and the same condition exists in cases of medicamentous argyria. The epidermis is a layer of pavement epithelium, from 0.08 to 0.12 mm. thick, united by cement-substance. The deepest layer, the mucous layer (d), rete Mal- pighii, consists of several layers of protoplasmic nucleated prickle-cells (R) , without membrane, pigmented in the colored races, as well as on the scrotum and at the anus, and of which the deepest are rather cylindrical and vertical. Among these cells scattered lymphatic wandering cells are encountered, which convey important constructive and nutrient material to the epithelial cells. On high -magnification the cells are found to be provided with a fibrillar structure. The interstices between the prickles serve as lymph-paths. The more superficial layers (b), stratum corneum, consist of flat, horny, non-nucleated, epidermic scales (E) that swell up in sodium hydrate. The division between these two layers is constituted by a layer especially distinct when the epidermis is thick of bright transitional forms of cells stratum lucidum (between b and d) . The uppermost layers of the epidermis are being continually desquamated, while new layers of cells resulting from division of the rete cells are constantly brought up from the depth. In this process, the cells that are elevated acquire the microscopic and chemical character of the horny layer, inasmuch as the nucleus un- dergoes atrophy. Wherever pigment is present in the epidermis itself and likewise in the epidermoidal structures, it is conveyed, in many situations, from the underlying connective tissue by the stellate wandering cells. In this way is explained the fact that pieces of epidermis trans- planted from a white person to a FlG - ' TO- Cutaneous Papillae Deprived of their Epidermis r^crrn cnrm Wv-nrnP rlarV TTI rpr and the Vessels Injected: a a a, tactile papillae, each con- taining a Meissner corpuscle. tain other situations, however as, for instance, on the mam- milla it can be shown that the pigment is formed in the deep epidermal cells themselves. Finally, the pigment in connective-tissue cells is said to be derived in part from that formed in the epidermal cells. In the layer of the epidermis in which the process of cornification takes place, therefore, from the upper layers of prickle-cells down to the actual cornified epidermis, the cells contain two varieties of granules the albuminoid, intracellular, hyaline granules, and the fat-like, extracellular granules of eleidin, which are exhibited in an analogous manner by all horny structures at the boundary of the process of cornification. The granules of eleidin can be stained with henna, the hyaline granules with hematoxylin. Both structures are said to be allied to chitin. Between the prickle-cells of the epidermis, and between the laminated epithelial cells of the mucous membrane, Herxheimer observed peculiar, spiral, solid fibers, which appeared to consist of fibrin-like masses. The elastic fibers of the horny .skin undergo hyaline swelling and scaly or granular disintegration as a phenom- enon of age. THE NAILS AND THE HAIR. The nails consist of numerous layers of firmly united cornified prickly epi- dermal cells, which can be isolated by caustic alkalies, and at the same time undergo swelling and display a nucleus (Fig. 178, n, m). The entire inferior surface of the nail rests upon the nail-bed. The posterior and the lateral borders are situated in a deep groove, the nail-fold (Fig. 180, called cell-bridges. The conduction of stimuli through unstriated muscles is at the same time thus explained. Where fibrils are visible in the fiber-cell (Fig. 189), they lie embedded in a rather homogeneous, granular substance, the sarcoplasm. According to Engel- mann, the disintegration of the substance of unstriated muscle into the separate spindle-shaped elements is a postmortem change in the tissue. The transverse, thickened areas occasionally observed are not due to transverse striation, but to partial contraction or fold-formation (Fig. 184, 10). Unstriated muscle-fibers also have tendinous insertions at times. The blood-capillaries pass in longitudinal meshes between the fibers, as do also the numerous lymph-capillaries that surround the cells. The motor nerves, according to J. Arnold, form a plexus of medullated and non-medullated fibers, partially supplied with ganglion-cells, and situated in the con- nective-tissue of the envelop surrounding the unstriated muscle-fibers the ground plexus. From this arises a second non-medullated plexus, with nuclei at the nodal points the intermediate plexus. This is situated either immediately upon the musculature or in the connective tissue between the individual bundles. The delicate fibrils (from 0.2 to 0.3 u) given off by this plexus unite to form still an- FIG. 190. Sensory Nerve in a Tendon. One fiber terminates in a Pacinian corpuscle (P), the other in a tendon- spindle of Golgi (G). other network, the intermuscular plexus, and pass to each fiber, running along its border and terminating in a pear-shaped thickening. According to Franken- hauser the fibrils terminate in the nucleolus; according to Lustig, in the vicinity of the nucleus; according to J. Arnold they traverse both fiber and nucleus and re-enter the plexus. P. Schultz describes also sensory nerves, connected with ganglion cells and provided with terminal nodules. In tendons the sensory nerves, after subdividing repeatedly, become non- medullated fibers (Fig. 190, a), which at the junction of muscle and tendon twine around or spread out over the bundles. This situation is covered with endothe- lium. The non-medullated fibers terminate finally in a tuft of delicate ramifica- tions, designated Golgi 's tendon-spindle. Terminations in the form of Pacinian corpuscles (P) or end-bulbs are also found in the tendons. PHYSICAL AND CHEMICAL PROPERTIES OF MUSCULAR TISSUE. The consistency of muscular tissue is similar to that of living proto- plasm; it is semi-solid, that is, not fluid to such a degree as to be diffluent, nor is so solid that confluence of separated parts would not be possible. The consistency, therefore, may be compared to that of a jelly at the moment of liquefaction. 548 PHYSICAL AND CHEMICAL PROPERTIES OF MUSCULAR TISSUE. The view expressed is supported by the following facts: (i) The analogy be- tween the function of the muscle-substance and that of the contractile protoplasm of cells, the latter surely possessing this semi-solid property, as must be inferred from the movement of the protoplasm. (2) The observation of the course of the contractile wave-movement through the length of the muscle-fiber. In the same category belongs the wave-like movement first observed by W. Kiihne, when a strong, constant current is passed through the muscle. The phenomenon depends upon the occurrence of slow contraction-waves within the fibers in the direction of the galvanic current, which are increased by heat, and disappear when the muscle is tightly stretched, or when its extremities are forcibly pushed together. (3) Under the microscope, the progression of a parasitic round-worm (Myoryctes Weismanni) has been observed to fake place by means of the serpentine move- ments through the contractile substance, the separated, semi-solid masses becom- ing again confluent behind it. Refraction of Light. The contractile substance refracts the light doubly (anisotropic) , while the ground-substance is singly refractive (isotropic). The contractile substance behaves like a doubly refractive, positively uniaxial body, whose optical axis corresponds with the longitudinal axis of the fiber. Under the polarization-microscope, with the Nicol's prisms crossed and the fiber so placed that the longitudinal axis intersects the vibration-planes of the Nicol's prisms at an angle of 45, the doubly refractive substance can be recognized by its ap- pearing bright in a dark field of vision, while in a colored field (purple-red from the interposition of a mica plate) it appears of another color (blue, yellowish-red, to yellow). Although the doubly refractive contractile substance undergoes change in form during contraction, its double refraction nevertheless persists unaltered. Catherine Schipiloff, A. Danilewsky, and O. Nasse believe that the contractile, anisotropic mass consists of myosin. According to the observations of Engelmann all contractile elements possess the property of double refraction, and the direction of shortening always corresponds with that of the optical axis. With respect to the actual cause of the anisotropy, the comprehensive investiga- tions of v. Ebner have demonstrated that as a result of the processes of growth in the tissue, tensions are produced (for example, the tension-phenomena of bodies subject to imbibition) that give rise to double refraction. During sustained contraction in degenerating muscle-fibers the refractive index of the muscle-substance is increased as a result of loss of water from the tissue and the consequent increased concentration of the dissolved parts of the muscle. The chemical composition of muscle undergoes rapid and profound changes after death. As, however, the muscles of the frog, when thawed after freezing, again become capable of contracting, they are, therefore, not altered chemically by the freezing. W. Kiihne cooled to 10 C. frogs' muscles rendered bloodless by means of a i per cent, sodium-chlorid solution, triturated them in an ice-cold mortar, and expressed the juice (which thaws at 3) through linen. The fluid thus expressed is filtered in the cold and appears as a slightly opalescent juice of a neutral or generally alkaline reaction and light yellowish tint, and designated muscle-plasma. In common with blood-plasma it coagulates spon- taneously. The muscle-plasma becomes at first uniformly gelatinous. Later, turbid, opaque, doubly refractive flakes and threads undergo con- traction in the jelly, and like the fibrin of the contracting blood-clot express a juice, muscle-serum, which has an acid reaction. Cold prevents the coagulation of muscle-plasma; above o it takes place but slowly, then more rapidly with increasing temperature, finally with great rapidity at 40 C. for the muscles of cold-blooded animals, or at 55 C. for those of warm-blooded animals. The addition of water or of a little acid to the muscle-plasma causes immediate coagulation. This coagulated proteid, the most abundant in the muscles, is derived from the doubly refractive substance, and is designated myosin. Its chemical formula is C 108 H 172 N 30 S0 33 . Myosin forms from 3 to n per cent, of moist muscular tissue. It can be METABOLISM IN MUSCLE. 549 extracted from muscle-juice by means of a 5 to 10 per cent, solution of ammon- ium chlorid. Myosin belongs to the globulins; Halliburton has prepared it also from the muscles of warm-blooded animals. It is precipitated from its solutions by saturation with sodium chlorid or magnesium sulphate. When dissolved in a 10 per cent, solution of sodium chlorid, it is coagulated by heat. It is dissolved by 2 per cent, hydrochloric acid, with the formation of acid-albumin (syntonin), and by alkalies or alkaline carbonates, with the formation of alkali- albuminate. Like fibrin, myosin actively decomposes hydrogen dioxid. A. Danilewsky has succeeded in reconverting syntonin in part into myosin. Myosin is not present in unstriated muscles. Muscle-serum contains further small amounts of myoalbumin (C 114 - H 17 4N 30 SO 30 ), which is coagulable at 73 C., but is not precipitated by sat- uration of the serum with magnesium sulphate ; also my o globulin, which is precipitated by this last procedure, and is coagulable at 63 C.; and a little nucleoalbumin. Halliburton distinguishes the following proteids in muscle: (i) Paramyosino- gen, or musculin, a globulin-like body, forming 20 per cent, of the total proteids, and coagulating at 47 C. (2) Myosinogen, forming 77 per cent, of the total proteids, coagulating at 55. Both of these bodies are coagulable spontaneously, forming myosin. (3) According to v. Furth myosinogen gives rise to myogen- fibrin, which is soluble, is coagulable at 35, and, like paramyosinogen, is readily transformed into a fibrin-like modification that is dissolved with difficulty. Cer- tain salts or organic substances (caffein, veratrin) accelerate this process, while it is inhibited by blood-serum, and also by egg-albumin. (4) Myoalbumin, which is similar to serum-albumin. The coloring-matter of muscle (myohematin) appears to be different from hemoglobin. The absorption-bands are situated somewhat nearer to the red end of the spectrum. According to Levy, myohematin is identical with hemochromogen. There is an oxidized and a reduced myohematin (by am- monium sulphid). The muscle-nuclei yield some nuclein. The sarcolemma con- tains a substance resembling keratin. Several ferments are present in traces: pepsin, diastatic, lactic-acid (?), glycolytic, and coagulating (fibrin-) ferments. Proteic acid is a proteid substance in the flesh of fish. The other chemical constituents of muscle have already been mentioned in the consideration of meat (p. 423). It will suffice to add a little more here, (i) In addition to volatile fatty acids (formic, acetic, and butyric acids), two isomeric lactic acids are found in muscle having an acid reaction : (a) Ethylidene-lactic acid in the modification of dextrorotatory paralactic or sarcolactic acid, (b) Ethylene- lactic acid in small amount, which Maly also observed develop as an occasional fermentation-product of carbohydrates (glycogen, etc.). The formation of lactic acid during the rigidity of death is discussed on p. 552. Acid potassium phosphate also contributes to the acid reaction. (2) Glycogen is found to the amount of i per cent, after an abundant meat-diet, and of 0.5 per cent, during fasting. During digestion it is stored up in the muscles, as well as in the liver, but it dis- appears in the state of hunger. It is formed in the muscles themselves, probably from albuminates. (3) Dextrose, 0.02 per cent. (4) Of gases, there are present carbon dioxid (from 15 to 18 vol. per cent., partly absorbed, partly in chemical combination, the latter probably being formed as a result of decomposition), some absorbed nitrogen; but no oxygen, although muscle continually absorbs oxygen from the blood. The muscles contain a substance that yields carbon dioxid on decomposition; exercise consumes this substance, so that muscles that are greatly fatigued are capable of generating less carbon dioxid. METABOLISM IN MUSCLE. THE SOURCE OF MUSCULAR ENERGY. The resting muscle continuously abstracts oxygen from, and returns carbon dioxid to, the capillary blood passing through it. Nevertheless, the muscle excretes less carbon dioxid than corresponds to the amount of oxygen it absorbs. Excised muscles deprived of blood exhibit an analogous but diminished interchange of gases. Further, as such muscles 550 THE SOURCE OF MUSCULAR ENERGY. retain their irritability longer in oxygen or in air than in indifferent gases free from oxygen, it is to be assumed that this gaseous interchange is a vital phenomenon connected with normal metabolism, and to which the functional activity of the muscle is due. The excised, resting, surviving muscle gives off carbon dioxid, which in part has been present in the muscle preformed, and in part is subsequently generated by processes of decomposition that accompany the development of rigidity. A small part of this carbon dioxid arises only when oxygen is supplied. Bacterial putrefaction of the muscles causes marked excretion of carbon dioxid. In active muscle the blood-vessels are always dilated, and the amount of blood passing through them is increased three or four times, a cir- cumstance that obviously indicates increased metabolic activity. Ac- cordingly, active is distinguished from passive muscle by a series of chemical changes: 1. The contents of living passive muscle have an alkaline, or, more correctly, a neutral reaction, changing red litmus to blue, but acid to turmeric paper. The reaction becomes acid in active muscle (not of the unstriated variety), and, indeed, the degree of acidity increases, to a certain limit, in proportion to the amount of work performed. The acidity is due to phosphoric acid resulting from the decomposition of lecithin and nuclein. The earlier view, that the acidity is due to the development of lactic acid produced from glycogen, has not been substantiated. Pfliiger and Warren, and also Astaschewsky and Heffter, even found the quantity of lactic acid in active muscles diminished, as compared with passive muscles. Other investigators, how- ever, still adhere to the theory of lactic-acid formation, especially if there is a deficiency of oxygen during the work. 2. The active muscle excretes considerably more carbon dioxid than the resting muscle: (a) Active muscular exertion in man or animals increases considerably the excretion of carbon dioxid from the body, (b) Venous blood flowing from the tetanized muscles of an extremity contains an increased quantity of carbon dioxid; and, indeed, under these conditions more carbon dioxid is excreted than corresponds to the amount of oxygen simultaneously absorbed, (c) Also, excised, con- tracted muscles excrete an increased amount of carbon dioxid. 3. Active muscle consumes a greater amount of oxygen: (a) During work the entire body takes up much more oxygen, even four or five times as much, (b) Venous blood flowing from the active muscles of an extremity contains a diminished amount of oxygen. Nevertheless, the increase in the consumption of oxygen by an active muscle is not so great as the increase in the excretion of carbon dioxid. The increase in the interchange of gases continues in the period of rest immediately following the activity. The consumption of oxygen can also be demonstrated volumetrically in excised muscles deprived of blood. It is true, oxygen is not absolutely necessary for muscular activity of short duration, as the excised muscle is capable of contracting for some time in a vacuum or in a gaseous mixture free from oxygen, and no free oxygen can be obtained from its tissue. The muscle must, therefore, contain a supply of oxygen in chemical combination, which is consumed during activity. Frogs' muscles ab- stract the oxygen from easily reducible substances; thus, they may de- colorize a solution of indigo. Muscles that have rested act less energet- ically than those that have been active. THE SOURCE OF MUSCULAR ENERGY. 551 4. An active muscle contains less extractives soluble in water, but, on the other hand, more of those soluble in alcohol. It also contains less of the substances that form carbon dioxid, less fatty acids, kreatin, krea- tinin, and sarcophosphoric acid. 5. During contraction the amount of water in muscular tissue is in- creased, while that in the blood is correspondingly diminished. The solid matters of the blood are increased, while those of the lymph (al- bumin) are diminished. 6. The question as to the extent to which the proteids of muscular substance generate the kinetic energy of muscular activity, by the trans- formation of their chemical potential energy, has been answered by Pfliiger with the statement that albumin, if given in sufficiently large amounts, may be the exclusive source of muscular force. This albumin represents a special variety, and is thought to be formed syn- thetically from ordinary living albumin by the absorption of alcohol-radicals, which may be withdrawn either from another proteid, or from fat and sugar if there is a deficiency of proteids. The living albumin is transformed into a readily decomposable, living proteid, which contains a greater amount of carbon, and represents the immediate source of muscular energy. If a lean dog, fed only with lean meat and in a state of metabolic equilibrium during muscular rest, is subjected to a period of several days' work, it must receive a definite excess of lean meat in order to maintain its bodily weight. During the period of activity, the animal, therefore, decomposes more proteid, in accordance with the extent of the activity, and the metabolic equilibrium is thus maintained. Undoubtedly the work performed is accomplished at the expense of an increased consumption of proteids. If the dog does not receive an increased quantity of proteids on beginning to work, it loses in bodily weight. Even though sufficient quantities of fat and carbohydrates, in addition to the proteid, be administered to the active dog, there will still be an increased con- sumption of proteids during work. As on administration of a sufficient amount of proteid the muscular work is performed with the aid of this alone, and as in the decomposition of this proteid neither fat nor carbohydrate results, the fat and carbohydrate cannot be the true source of muscular force (Pfliiger) . The carbon dioxid resulting from the decomposition of proteid leaves the body quickly through the pulmonary respiration; while the nitrogenous products of decomposition are excreted slowly, even for as long as two days after the com- pletion of the work. One and the same readily decomposable proteid is thus oxidized slowly and continuously in the muscular tissue, with the generation of heat, while under the influence of innervation it is consumed rapidly and in larger amount, and is then the source not only of heat, but also of kinetic energy. Pfliiger estimated that in his experimental dog one gram of nitrogen in the Sroteid, decomposed within the body, produced 7456 kilogrammeters of work. f the total supply of energy contained in the proteid (measured by means of the calorimeter in calories), the dog converted 48.7 per cent, into kinetic energy, the remainder being transformed into heat. This 48.7 per cent, represents the mechanical equivalent of the proteid. At an earlier period Fick and Wislicenus, as well as v. Voit and v. Pettenkofer, had reached the conclusion as a result of their experiments that the daily excretion of nitrogen is not increased to any considerable extent by forced work, whereas the consumption of oxygen and the excretion of carbon dioxid are increased, provided that the body' has at its disposal sufficient material containing carbon, such as glycogen and fat, in its tissues or in the food. Hence, the proteid cannot be the source of muscular energy. Increased elimination of nitrogen takes place only when the activity gives rise to dyspnea, for deficiency in oxygen causes decomposition of albuminates. Also the increased excretion of sulphuric acid resulting from work is indicative of 552 MUSCULAR RIGIDITY. a more active decomposition of albuminates. The excretion of sulphur is increased by muscular exertion, and indeed the non-oxidized sulphur is at first excreted more rapidly than the oxidized. The excretion of phosphoric acid also is in- creased. 7. In the muscles of animals the amount of glycogen (0.43 per cent.) has been observed to diminish as a result of activity, and even to dis- appear completely in consequence of strychnin-convulsions. The same observation has been made with respect to the glycogen of the liver. Luchsinger maintains that muscles can still contract when completely free from glycogen; so that the latter cannot be the source of muscular energy. Also, the sugar of the blood undergoes a decrease in the muscles as a result of activity. There is a difference of opinion as to whether the muscle-glycogen is carried by the circulation from the liver into the muscles, or whether it is produced in the muscular tissue itself as the result of an as yet unknown decomposition of the albuminates. Ktilz observed an increase in the amount of glycogen in the muscles of frogs that had been deprived of their livers after subcutaneous injections of sugar. Likewise, the muscles retained their glycogen for a much longer time than the liver during the state of hunger. These facts indicate the formation of glycogen in the muscular substance itself. In any event, the normal circulation is a requisite for the production of glycogen in muscle, for this diminishes after liga- ture of all of the vessels. Surviving muscle converts glycogen into sugar. Some investigators, however, assume also that not only proteid but, in part, also fat and carbohydrate may be the source of muscular energy in the body. MUSCULAR RIGIDITY (CADAVERIC RIGIDITY, RIGOR MORTIS). Excised muscles, striated as well as unstriated, and also the muscles of the intact body some time after death, pass into a state of rigidity, described more fully later on, that is designated muscular rigor. If the muscles of the dead body become involved, the entire cadaver be- comes completely stiff (cadaveric rigidity). The cause of this phenome- non resides in a spontaneous coagulation of the myosin within the muscle- fibers, with the development of a small amount of acid. During this process of coagulation, heat is liberated owing to the transition of the fluid myosin into the solid condition, and, also, owing to the thickening of the tissue that takes place at the same time. Myosin, dissolved in a 5 per cent, solution of magnesium sulphate diluted with water, separates after a time in the form of solid flakes, with the development of an acid reaction. Warming hastens this process. _ The rigid muscle exhibits the following properties: It is shortened, thickened, and somewhat denser; stiff, firm and solid; turbid and opaque, in consequence of the coagulation of the myosin; incompletely elastic, less extensible, and less readily torn. It is completely unresponsive to stimuli, and its electrical potential has disappeared. The amount of glycogen present is diminished. Striated muscle has an acid reaction, on account of increased formation of the two varieties of lactic acid (un- striated has not), and it develops free carbon dioxid. If incisions be made into rigid muscles, a fluid exudes spontaneously, the muscle- serum. The view was formerly held that during rigidity, partial or complete trans- formation of the glycogen occurred, first into sugar and then into lactic acid. This view, however, has been contested by Bohm, who asserted that during MUSCULAR RIGIDITY. 553 digestion a transitory accumulation of large amounts of glycogen takes place in the muscles, as in the liver; so that approximately as much can be found in the former as in the latter. Rigidity causes no diminution of glycogen, provided putrefaction is prevented; < hence, the lactic acid of rigid muscles cannot arise from glycogen, but probably from decomposition of albuminates. Heffter main- tains that lactic acid is not formed at all during postmortem rigidity. The amount of acid does not vary, whether the rigidity develops slowly or rapidly. With the onset of acidification, the rigidity becomes more marked, on account of the coagulation of the alkali-albumin in the muscle. The less carbon dioxid there is generated by the rigid muscle the more it had already given off previously during activity. Fibrin-ferment is present in muscle in a state of cadaveric rigidity. It is in general a product of protoplasm, and is never wanting where the latter is present. There is thus an analogy between coagulation of blood and muscular rigidity. Two stages of rigidity are to be distinguished: In the first stage the muscle is already somewhat stiff, but still excitable; the myosin in this stage acquires a gelatinous consistency. Restitution is still possible from this stage. In the second stage the rigidity is fully developed in all of the characteristics mentioned. Rigidity appears in man in from ten minutes to seven hours; the duration is likewise variable, from one to six days. After its disappearance, the muscles again become soft, owing to the onset of further decomposition and an alkaline reaction; the rigidity yields. The onset of rigidity is always preceded by a dis- appearance of nervous activity. Therefore, the muscles of the head and the neck are first affected, and then the others in a descending order. Likewise those muscles that usually degenerate earliest a are the first to become rigid; for example, in the frog the flexors before the extensors. Rigidity disappears earliest also in those muscles that first became rigid. Great muscular activity before death, for example during the convulsions of tetanus, cholera, strychnin-poisoning, or opium- poisoning, causes rapid and intense rigidity. Therefore, the heart becomes strongly rigid and with relative rapidity. White muscles become rigid later than red muscles. Wild animals, hunted to death, may become rigid in a few minutes. Usually the rigidity lasts the longer the later it sets in. Rigidity never occurs in the fetus before the seventh month. Frogs' muscles cooled to o C. become rigid only after from four to seven days. Stenson's Experiment. The influence of the amount of blood in the muscles upon the onset of rigidity is especially worthy of notice. Ligation of the muscular arteries in warm-blooded animals causes first increased irritability of the muscular tissue, lasting a few minutes, then rapid diminution in the irritability, followed by the onset of both stages of rigor in succession. If the arteries of the muscles were ligated, Stannius observed that the irritability of the motor nerves disap- peared in the course of an hour, that of the muscular tissue itself in from four to five hours; then rigidity sets in. Pathological. Thrombotic occlusion of the muscular vessels will also cause rigidity. Excessively tight bandaging may give rise to true rigidity in man by cutting off the circulation. The muscles become paralyzed and stiff, and later break up into flakes, and the contents of the fibers are subsequently absorbed. The circu- latory disturbances, arising in muscles under the influence of cold, also cause paralyses that are often designated rheumatic. Also in cases of trichinosis the affected muscle-fibers are the seat of rigidity, and the stiffness in the muscles is thus explained. The contractures occurring in cases of cholera should probably be included in the class of muscular contractions resulting from circulatory dis- turbances, the inspissated blood giving rise to stagnation; as should also certain contractions occurring in the presence of atheroma and in the agonal period. The sensory nerves in completely anemic extremities retain their irritability for from five to ten hours. If the circulation be restored in the first stage of rigidity, the muscle soon recovers. If, however, the second stage has set in, restitution is impossible. In cold-blooded animals rigidity does not set in for several days after ligature of the vessels. Brown-Sequard, by the injection of fresh blood containing oxygen, succeeded in restoring softness and irritability to a human cadaver in the first stage of rigidity even four hours after death. Heubel obtained the same result with the frog's heart as long as fourteen and one-half hours after death. On pass- 554 MUSCULAR RIGIDITY. ing blood containing oxygen through excised muscles, C. Ludwig and Al. Schmidt found that the onset of rigidity was retarded for a long time; this did not occur, however, with blood deprived of oxygen. After considerable loss of blood, rigidity sets in relatively early. If an artificial circulation be kept up in the dead muscles of a frog by means of feebly alkaline fluids, rigidity does not occur. Previous section or paralysis of the motor nerves results in delayed onset of rigidity in the relaxed muscles. The reason is found in the greater abundance of blood in these muscles, in consequence of associated paralysis of the vasomotors, the alkaline blood remaining in the muscles even after death, while the arteries in other parts of the body become empty. This view is supported by the fact that rigidity appears much later in fish whose medulla oblongata is suddenly destroyed than in those that die slowly. According to Ewald and Willgerodt the labyrinths of the ear, as organs controlling tone, likewise have an influence on the course of rigidity. Freezing and thawing cause rigidity to set in more rapidly, and it is favored likewise by mechanical injury. Continuous passive movements may retard the onset of rigidity, but on their cessation their rigidity sets in all the more rapidly. Rigidity that has already developed may be overcome by forced movements, but it may set in again. Rigidity may be induced artificially: 1 . By heat (heat-rigor) , which causes coagulation of the myosin in cold-blooded animals at 40, in mammals at from 45 to 47 C., and in birds at about 53 C. Under such circumstances there is marked excretion of carbon dioxid, but less after previous tetanization. Protoplasm, for example of the amoeba, is similarly subject to heat-rigor. The degree of heat required to bring about rigidity is the higher the longer the muscles have been excised. If the muscles of a frog in a state of cadaveric rigidity be heated, the remaining proteids undergo coagulation successively, and the muscle becomes still more rigid as a result of these coagulative processes. 2. Saturation with water induces water-rigor, with the development of an acid reaction, in consequence of the coagulation of the globulin-substances, the excretion of carbon dioxid not being increased. If the thigh of a frog be ligated, and the muscles, deprived of their skin, be immersed in warm water, they will become rigid. On loosening the ligature a slight degree of rigidity may disappear through restoration of the circulation. On the other hand, a more marked degree of rigidity can be removed only by placing the leg in a 10 per cent, solution of sodium chlorid, which will dissolve the myosin- coagulum. 3. Acids, even weak acids such as carbon dioxid, induce rapid acid-rigor. This is probably different from normal rigidity, as the muscle does not develop free carbon dioxid. Injection of from o.i to 0.2 per cent, solutions of lactic or hydrochloric acid into the vessels of frogs' muscles causes immediate rigidity, which can be overcome by 0.5 per cent, acid, and also by a neutralizing solution of sodium bicarbonate, or 13 per cent, solution of ammonium chlorid. The acids enter into combination with the myosin. 4. Among poisons and other substances, the following promote rigidity: Caffein, quinin, digitalin, veratrin, hydrocyanic acid, also oils of mustard, fennel, and anise, and, when placed in direct contact with the muscles, potassium sulpho- cyanid, ammonia, metallic salts, alcohol, ether, chloroform. Chloroform, acetic acid, and heat induce rigidity with shortening; ammonia, on the other hand, rigidity without shortening. The position of the entire body during rigidity is usually that which it occupied at death. The position of the limbs corresponds to the resultant of the various degrees of muscle-tension. If the limbs occupied another position before death, they are frequently seen to move during the onset of rigidity. The arms and fingers especially are readily flexed. If the rigidity develops with especial firmness and rapidity in certain groups of muscles, an unusual position may be assumed, for example the fencing attitude of cholera-cadavers. If the rigidity occurs rap- idly, the body at times remains in the same position that it occupied at the moment of death, for example on the battle-field. Under such circumstances, however, the contracted muscle never passes immediately into a condition of rigidity, a period of relaxation intervening, even though short. Muscles scalded by immersion in boiling water do not become rigid; neither do they become acid, nor evolve free carbon dioxid. Muscles coagulated by concentrated alcohol or by immersion in concentrated solutions of sodium chlorid , potassium nitrate, sodium and magnesium sulphate, do not yield an acid reaction. IRRITABILITY AND STIMULATION OF THE MUSCLE. 555 Attention has repeatedly been directed to the analogies between muscle in active contraction and in the state of rigidity- The form of the contracted and of the rigid muscle is shortened and thickened; both are denser, of changed elas- ticity, and evolve heat; the contents of the contracted as of the rigid muscle are negative electrically as compared with resting or non-rigid contents; both evolve free carbon dioxid and the remaining acid from the same source. A contraction may, therefore, be regarded as a temporary rigidity, disappearing physiologically, just as earlier investigators, and recently Bernstein, designated rigidity as being, to a certain extent, the final vital act of the muscles. A muscle in process of becoming rigid will lift a weight, like a living, con- tracting muscle. The height to which the weight is lifted by a rigid muscle is greater in the case of small weights and less for heavy ones than if the living muscle be stimulated to a maximum degree. If a muscle, in which heat-rigor has been induced, be at first prevented from contracting 1 , and if later (for example after ten minutes) it be set free, its elastic energy will cause it to contract, and it must lose heat at the same time. The disappearance of cadaveric rigidity takes place at first as a result of increased formation of acid in the muscle, by which the myosin is redissolved. Subsequently, with the development of micro6rganisms putrefaction sets in, with the associated evolution of ammonia, hydrogen sulphid, nitrogen, and carbon dioxid. The loss of irritability in the muscles that precedes the onset of rigidity occurs in the following order in man (beheaded criminal): Left ventricle, stomach, intes- tine (fifty-five minutes), urinary bladder; right ventricle (sixty minutes); iris (one hundred and five minutes) ; muscles of the face and the tongue (one hundred and eighty minutes) ; the extensors of the extremities about one hour before the flexors ; the muscles of the trunk (from five to six hours) . The esophagus remains irritable for a long time. IRRITABILITY, STIMULATION, AND DEATH OF THE MUSCLE. By the irritability of a muscle is understood, its ability to contract in response to stimuli applied directly to it (not to its nerves). Stimu- lation is the state of functional activity in which a muscle is placed by stimuli. At the moment of activity the stimulation causes the chemical potential energy of the muscle to be converted into work and heat; stimuli thus act as liberating forces. The mean temperature of the body is most favorable for the manifestation of irritability. Each muscle appears to possess a special degree of irritability peculiar to it- self, as do likewise the nerves. So long as the current of blood in the muscle is uninterrupted, stimu- lation first causes an increase in its functional activity, partly because the circulation becomes more active in association with dilatation of the vessels; later, however, the functional activity diminishes. This diminution in functional activity is a sign of fatigue. If the same stimu- lation be continued, the muscular activity will exhibit a periodic variation, in such manner that after a series of weaker contractions stronger ones will again set in, followed in turn by weaker, and so on. This phenomenon depends upon periodically recurring improvement in the nutrition of the muscle, as a result of analogous variations in its circulation. In excised muscles also, especially if the large nerve-trunks have al- ready undergone degeneration, the irritability is at first somewhat in- creased after each stimulation, so that with a uniform series of stimuli the contractions at first exhibit an increase in extent. Thus, it may happen that, while the first weak stimulus is still ineffectual, the second will give rise to a contraction. The unstriated muscles exhibit, under certain conditions, automatic and rhythmic movements without the intervention of nerves. 556 IRRITABILITY AND STIMULATION OF THE MUSCLE. Frogs' muscles that have been cooled, or those in which desiccation has begun, exhibit an excessively increased irritability, especially to mechanical stimuli. This fact may explain the remarkable muscular movements that often take place in cholera-cadavers. Cooled muscles from the frog or the tortoise may preserve their irritability for as long as ten days, but the muscles of warm- blooded animals often degenerate in from one and one-half to two and one-half hours. The irritability of the heart-muscle is considered on p. 118. Curarized, isolated frogs' muscles exhibit the least amplitude of contraction at o, the greatest at 30; if heated beyond the latter temperature, the contraction gradually dimin- ishes, until the point is reached where rigor sets in. The duration of contraction and the latent period are also shortest at 30. Since the time of Alb. v. Haller (1743) it has been thought necessary to attribute to muscle a peculiar irritability (even without the intermediation of the motor nerve) . In more recent times attempts have been made to adduce further support in favor of this specific muscular irritability: (i) There are chemical irritants that induce no movement when applied to the motor nerves, but cause contraction when applied directly to the muscle; for example ammonia, lime- water, carbolic acid. (2) The extremities of the sartorius muscle of the frog, in which no nerve-endings can be demonstrated by means of the microscope, never- theless react to direct stimulation by contractions. (3) Curare paralyzes the motor nerves, while the muscle itself remains irritable. The action of cold, or the arrest of the circulation in the muscle of an animal, will likewise abolish the irritability of the nerve, but not of the muscle at the same time. In general, the directly stimulated muscle will still contract for some time after its motor nerve has degenerated. (4) After section of the nerves, the muscles still remain irritable, even though the nerves have undergone total fatty degeneration. (5) At times electrical stimuli act only upon the nerves, and not upon the muscles them- selves. In lower animals (hydra, medusa) unicellular structures, neuro-muscular cells, have been found in which nervous and muscular tissue are represented in one and the same cellular structure. With regard to the stimuli that act upon the muscles, the following are to be noted: 1. The normal stimulus under ordinary circumstances acts upon the muscle by way of its nerve, as in voluntary movement, the automatic motor impulse, reflex excitation. Its nature is unknown. The irritation of a muscle through the intermediation of its nerve is designated indirect stimulation. Pseudomotor effects are considered on p. 559. 2. Chemical Stimuli. All chemical agents that alter the chemical constitution of muscular tissue with sufficient rapidity act as muscle-stimuli. According to Kuhne, the mineral acids (o.i per cent hydrochloric acid), acetic and oxalic acids, the salts of iron, zinc, copper, silver, and lead, bile, all act as stimuli to the muscle in dilute solution, and only on the nerves in much stronger solutions. Lactic acid and glycerin, when concentrated, excite only the nerve (?) ; when dilute, only the muscle. The neutral alkaline salts act equally on muscle and nerve. Alcohol and ether both act feebly. Water, especially if injected into the muscular vessels, causes fibrillary contractions. Solutions of sodium chlorid, from 0.6 to 0.9 per cent., or normal solutions of other sodium-salts, act indifferently toward the muscular substance, even after the latter is exposed to their influence for days; this is especially true after the addition of a trace of calcium chlorid or calcium phosphate. A 6 per cent, solution of sodium chlorid causes the sartorius, when deprived of its nerve, to contract much more strongly than when its nerve is preserved, and especially in its active, thick fibers. Acids, potassium-salts, and meat-extract diminish the irritability of the muscle, while other muscle-stimuli, such as alcohol, sodium-salts, some metallic salts, in small doses increase the irritability. Gases and vapors also have a stimulating influence on the muscles, either exciting simple contractions or immediately causing contracture. Pro- tracted exposure to the gases causes rigidity. Only the vapor of carbon disulphid has an irritating effect on the nerves, while most vapors (for example, of hydro- chloric acid) destroy without causing excitation. In comparative observations on the influence of chemically related substances, only chemically equal quantities, for example normal solutions, should be employed. Thus, among the halogens, sodium iodid, with its high molecular weight, has the strongest effect; while sodium chlorid, with its low molecular weight, has the feeblest effect. The combinations of the metals act in like manner; also the salts of the alkaline earths. Those with the highest molecular weight cause the IRRITABILITY AND STIMULATION OF THE MUSCLE. 557 greatest excitation and the least injury. The following substances cause injury in the order of their sequence, arranged from those with stronger to those with weaker effects: ammonia, potassium, sodium, hydrochloric acid, nitric acid, sulphuric acid, phosphoric acid (in accordance with their avidity) ; the fatty acids with larger molecules as compared with those with smaller; the higher alcohols as compared with the lower. In making experiments upon the chemical irritation of "muscles, it is inad- visable to immerse the transverse section of the muscle in the solution. The substance in solution should rather be applied to a limited area on the uninjured surface of the muscle. The stimulation will then be manifested in a few seconds by contraction or fibrillary motion of the superficial muscular layers. If the sartorius of a curarized frog be immersed in a solution of 5 grams of sodium chlorid, 2 grams of alkaline sodium phosphate, and 0.5 gram of sodium carbonate in i liter of water at 10 C., the muscle will be thrown into rhythmic contractions, which may persist even for days. These contractions suggest, to a certain degree, the rhythmic action of the heart (Biedermann). The following act as chemical irritants upon unstriated muscles: ergot, aloes, colocynth, the alkalies; atropin and nicotin paralyze the nervous elements in such muscles, as does also ether; chloroform also destroys the muscle-fibers them- selves. Carbon dioxid in small amounts acts as an irritant to the nerves, in larger amounts as a paralyzant, and in still larger amounts it irritates and finally paralyzes the muscle-fibers themselves. 3. Thermal Stimuli. If a frog's muscle be rapidly heated, a gradually in- creasing contraction begins at about 28 C., becomes more pronounced at 30 C., and attains its maximum at 45 C.; following this, further heating rapidly leads to heat-rigor. Local cooling of the muscle increases its irritability for all kinds of stimuli. Frog's muscle cooled to o is exceedingly responsive to me- chanical irritation, and it may be stimulated by degrees of cold below o, until freezing takes place. Heat has a relaxing effect on unstriated muscle (frog), while cold has a moderately stimulating effect. Variations in temperature, how- ever, also affect the nerves of these muscles, each fluctuation causing reflex con- traction, which does not occur if the nerves are paralyzed. Cl. Bernard made the remarkable observation that the muscles of artificially cooled animals retain their irritability for many hours after death. Heat causes rapid disappearance, with temporary increase of the irritability. 4. Mechanical stimuli of all kinds cause a contraction at each separate, sudden blow; and tetanus if repeated. Strong, local stimuli induce an elevated contrac- tion of considerable duration at the point of application. Moderate stretching of a muscle increases its irritability. Mechanical stimulation of a muscle poisoned with veratrin causes a heaving movement of its fibers, which may persist for as long as one minute. 5. Electrical stimuli are discussed in conjunction with nerve-stimuli (p. 631). Curare, the arrow-poison of the South American Indians, is the dried juice of the root of Strychnos Crevauxi. When introduced into the blood or injected subcutaneously, it first causes paralysis of the intramuscular termination of the motor nerves, the muscles themselves retaining their irritability, while the sensory nerves and those of the central organs and the viscera (heart, intestine, and ves- sels) remain for a time unaffected. In warm-blooded animals the paralysis of the respiratory muscles naturally causes early asphyxia, which is unattended with convulsions. Frogs, whose skin is their most important respiratory organ, on receiving a suitable dose, may recover completely, after remaining motionless for days, during which the poison is eliminated through the urine. Larger doses paralyze also the cardiac inhibitory and vasomotor nerves. In electrical fish paralysis of the nerve transmitting the electrical shock occurs. In frogs the lymph-hearts also are paralyzed. If the doses that are fatal when administered subcutaneously be given by mouth, poisoning does not result, because the poison is eliminated by the kidneys at the same rate that it is absorbed by the gastric mucous membrane. For the same reason the flesh of an animal killed by a poisoned arrow is harm- less. If, however, the ureters be ligated, the poison accumulates in the blood, and intoxication results. Large doses, however, will kill uninjured animals also by way of the intestinal tract. Atropin appears to be a specific poison for unstriated muscle-fibers, although different muscles are variously affected by it. The irritability of the muscles after lesions of the nerves deserves especial attention. After three or four days the irritability of the paralyzed muscle is diminished for direct or indirect (nerve) stimuli. There then follows a stage in 558 CHANGE OF SHAPE IN ACTIVE MUSCLE. which a constant current has an abnormally excessive effect, while induced cur- rents are almost or completely without effect; irritability to direct, mechanical stimuli is also increased. This increased irritability is observed at about the seventh week. It then diminishes gradually, until it completely disappears at about the sixth or seventh month. Beginning with the second week, the muscle begins to undergo progressive fatty degeneration, to the point of complete atrophy. In experiments on animals Schmulewitsch found, immediately after section of the sciatic nerve, that irritability was increased in the muscles innervated by it. After death the muscles degenerate (excised muscles more rapidly), and the earlier if they have been exhausted and exposed to stimuli of considerable intensity. Thick muscles "survive longer (in their inte- rior) than thin muscles. It would appear that there is a definite stage of early or late death for each individual muscle; for example, the extensors in man degenerate earlier than the flexors. The muscles of the frog degenerate in twenty-four hours at summer tem- perature, in the course of two or three days at moderate temperature, and only after about twelve days at o. The muscles of warm-blooded animals degenerate on an average in the course of from one-sixth to twelve hours. The degeneration of the heart is considered on p. 113. CHANGE OF SHAPE IN ACTIVE MUSCLE. Macroscopic Phenomena. i. Active muscle becomes shorter and at the same time increases in thickness. The degree of shortening, which in exceedingly irritable frogs may amount to as much as from 65 to 85 per cent, (on an average 72 per cent.) of the entire length of the muscle, depends upon various factors: (a) To a certain degree an increase in the strength of the stimulus gives rise to a greater amount of shortening. (6) With increasing exhaustion after continuous, vigorous activity, the same strength of stimulus causes less shortening, (c) Elevation of temperature up to 30 C. causes stronger contractions in the frog's muscles. If the temperature be further elevated the degree of shortening is again diminished. 2. The contracting muscle is somewhat diminished in volume. Con- sequently, the specific gravity of contracting muscle is somewhat in- creased, the ratio to that of non-contracting muscle (in the marmot) being as 1062 : 1061. The diminution in volume amounts to only T ^ T - Method. Swammerdam placed a frog's muscle in a glass tube containing air and drawn out into a thin tubule containing a small drop of fluid. The nerve was conducted to the exterior through a small lateral opening. Mechanical stimulation of the exposed nerve caused contraction of the muscle and descent of the small drop. In an analogous manner Ermann placed irritable fragments of an eel in a similar tube, filled with an indifferent fluid. The fluid rises to a certain level in a thin tubule communicating with the glass container. When the muscu- lature of the eel was made to contract, the fluid sank. Landois demonstrated the diminution in volume of contracted muscle by means of the manometric flame. The cylindrical glass vessel containing the muscle receives two electrodes passing through its walls in an air-tight manner. It communicates at one point with a gas-supply pipe, and at another point it gives off a thin tubule, at the extremity of which a small flame is ignited at low gas-pressure. The muscular contraction following each electrical stimulus causes a reduction in the size of the flame. If a pulsating heart, naturally containing no air, be placed in the gas- chamber, each pulsation will be attended with a reduction in the size of the flame. 3. Under normal conditions, all stimuli applied to the muscle, as well as to the motor nerve, will cause contraction in all of its fibers. The muscle thus conducts to all of its fibers the impulses communicated to it. Deviations from this rule are observed, however, in two direc- tions: (a) When the muscle is greatly exhausted, or when it is about CHANGE OF SHAPE IN ACTIVE MUSCLE. 559 to degenerate, a violent mechanical, and also a chemical or electrical stimulus, applied to a circumscribed portion of the muscle will cause contraction in this portion alone; so that an elevated thickening of the fibers (Scruff's idiomuscular contraction] is observed at this point. The same phenomenon may be induced in the muscles of a healthy person, and especially in weakened and poorly nourished individuals, if the fibers be struck with a blunt edge at right angles to their course, (b) Under certain conditions, as yet not fully known, the muscles will be seen to exhibit so-called fibrillary contractions, that is the various bundles of fibers in the muscle are from time to time traversed by short contractions. Such a condition is observed in the tongue -muscles of the dog after section of the hypoglossal nerve, and in the face-muscles after section of the facial nerve. According to Bleuler and Lehmann, section of the hypoglossal nerve in the rabbit is followed in the course of from sixty to eighty hours by fibrillar con- tractions that persist for months, even when stimulation of the healed nerve above the point of union again excites movements in the corresponding half of the tongue. Stimu- lation of the lingual nerve increases the fibrillar contractions. This nerve contains vasodilator fibers from the chorda tympani. Schiff believes that the cause of the contractions resides in the increased blood-supply to the tongue. Sigm. Mayer also observed contractions in the facial muscles in rabbits, after restoration of the cir- culation in the carotids and subclavians, pre- viously compressed. Section of the motor nerves in the face does not abolish the phenomenon, while repeated compression of the arteries does FIG. 191. The Microscopic Phenomena SO. The Cause Of the contractions resides, ac- of Muscular Contraction in the Indi- cordingly, in the musculature itself. This motor EnSSLS?* 8 f the Fibrils (after phenomenon is designated pseudomotor. It may be compared to the paralytic secretion of the salivary glands. Similar phenomena have been observed also in man under pathological conditions, but at times fibrillar contractions may be observed even in the absence of other evidence of pathological disturbances. Microscopic Phenomena. i. The separate fibrils of the muscle exhibit the same phenomena as does the entire muscle, in that they be- come shorter and thicker. 2 . The observation of the individual muscle- elements is attended with especial difficulties. In the first place, it is certain that during contraction they become collectively shorter and thicker, so that the transverse striations appear to be pushed more closely together. 3. Opinions are not fully in accord as to the behavior of the constituent parts of each muscle-element during contraction. Fig. 191,1 represents, according to Engelmann, on the left a muscular element at rest; from c to d extends the doubly refractive, contractile substance, in the middle of which the median disc a b is situated; h and g are the terminal discs. In addition, there is in each singly refractive light layer an accessory disc, f and e, which is doubly refractive in but slight degree, and occurs only in the muscles of insects. Fig. i shows on the right the same element in polarized light, the middle portion of the element, so far as the actual contractile substance extends, appearing light on account of the double refraction; while the remainder of the muscle-element appears black on account of the single refraction. Fig. 191, 2 represents the transition-stage, and 3, the actual contractile stage of the muscle- element, both on the left as viewed in ordinary light, and on the right in polarized light. According to Engelmann, during contraction (3) the singly refractive layer becomes on the whole more highly refractive, and the doubly re- 560 THE TIME RELATIONS OF MUSCULAR CONTRACTION. fractive layer less so. As a result, the fiber may with a certain degree of shortening (2) appear homogeneous and only faintly striated when observed in ordinary light, the homogeneous or transitional stage (Mer- kel's stage of dissolution). If the shortening be more pronounced (3), distinct dark striae again appear, corresponding to the singly refractive discs. At every stage of shortening, including, therefore, the transition- stage, the singly and doubly refractive layers may be demonstrated, by means of the polarizing apparatus, as sharply defined, regularly alternat- ing layers (in i, 2, 3, to the right). They do not exchange places in the muscle-compartment during contraction. The height of both layers is diminished during contraction, that of the singly refractive much more rapidly than that of the doubly refractive layer. The total volume of each element is not appreciably changed during contraction. There- fore, the doubly refractive layers increase in volume at the expense of the singly refractive layers. Hence it follows that during contraction fluid passes from the singly into the doubly refractive layer; the former shrinks, the latter swells. Method. The phenomena described can be best observed by instantaneously coagulating the living muscle-fibrils of insects in the various stages of rest or contraction by suddenly applying alcohol or dilute perosmic acid to the muscles, and thus fixing the different stages. The movement itself may be followed under the microscope, either by stimulating the thin, outspread muscle electrically, or, still better, by observing the independent muscular contractions in the trans- parent parts of an insect, for example in the head of the gnat's larva. A thin, extended muscle, for example the sartorius of the frog, yields a double spectrum (like a Nobert's glass screen), if light be allowed to pass through a narrow slit, held closely in front of the fibers and at right angles to them. If the muscle be made to contract, for example by mechanical stimulation, the spectrum broadens, an evidence that the intervals between the transverse stria? become smaller. At the same time the transparency of the muscle becomes greater than during rest. THE TIME-RELATIONS OF MUSCULAR CONTRACTION. MYOGRAPHY. SIMPLE CONTRACTION. TETANUS. ISOTONY. ISOMETRY. Isotonic muscular activity is the term applied to the contraction in which the tension of the muscle remains the same, while the fibers be- come shorter. Method. The time-relations of the contraction in the isotonic muscular act may be shown by v. Helmholtz's myograph (Fig. 192). The suspended muscle (M), fastened at its upper extremity (K), is attached by its lower extremity to a lever constructed like a balance, which can be weighted by means of the weights (W) as desired, and is raised by the shortening of the muscle. From the free extremity of the arm of the lever is suspended by means of a hinge- joint a style (F), which records the movement of the lower extremity of the muscle on the smoked surface of a cylinder made by means of clockwork to rotate at a uniform speed in front of the style. In this way the contracting muscle itself records its contraction-curve, in which the abscissas represent the units of time calculated from the known rapidity of rotation of the cylinder, and the ordinates represent the degree of shortening at any particular moment. Fick improved the myograph materially by making the writing lever ex- ceedingly light, and applying the weight close to the rotation-axis of the balance. In this way the swinging movement accompanying the muscular contraction is reduced to a minimum, as is also the change in tension brought about by such movements. The surface intended for the reception of the myogram must be moved rapidly, as the process of movement takes place rapidly. Therefore, either a plate fastened ISOTONIC MUSCULAR CONTRACTION. to the rod of a pendulum (Pick's pendulum-myograph) , or a surface set in motion by gravity (Jendrassik's gravity-myograph) or by means of a spring (Du Bois- Reymond) or a rotating convex surface (Rosenthal's rotating myograph) , may be employed. Under the myogram a time-curve is traced by means of a vibrating tuning-fork. The apparatus is, in addition, provided with an arrangement for indicating in the tracing the moment of stimulation. The curve may be traced advantageously on the vibrating plate of a tuning- fork (Fig. 194, I). The time-units are thus registered in all parts of the curve, each complete vibration being equal to 0.01613 second. The moment of stimula- tion coincides with the beginning of the vibration of the fork, which is at first moved to one side for a time, without vibrating. This is accomplished by re- leasing a clamp, which at the same time opens a galvanic circuit, and sends an induction (opening) shock of the secondary coil through the muscle. The tuning- fork can also be set in vibration by a blow on one of its prongs. If under such circumstances the nerve is so placed upon the fork as to be struck by the blow, the latter acts at the same time as a mechanical nerve-stimulus. The balance, together with the imposed weights, is jerked upward at the commencement of the contraction. As a result the curve is distorted, because the muscle is no longer weighted after the moment of occurrence of the jerk. For this reason the muscle has been made to draw up an elastic spring. In this way, however, a stronger pull must be made on the muscle as the spring is raised higher and higher. To avoid this Grutzner constructed a spring that exerts a steadily diminishing tension on the apparatus as the muscle pro- gressively contracts. If it be desired to record only the extent (height) of the contrac- tion, the tracing is made on a stationary surface, which is dis- placed slightly after each move- ment (Pfliiger's myograph) . Muscular contractions may also be recorded in the case of man. It is best to transfer the increase in thickness attending contraction either to a lever or to a drum covered with rubber, for example that of Brondgeest's pansphygmograph (p. 101). FIG. 192. Diagrammatic Representation of v. Helmholtz's Myograph: M, the muscle, fastened at K; F, the writing- style, suspended from the arm of the lever that is to be raised; P, a counter-weight for maintaining equilibrium; W, scale-pan for weighting the muscle as desired; S S, posts supporting the balancing lever. If a single stimulus of momentary duration be ap- plied to a freely movable mus- cle, the latter executes a simple contraction, that is it shortens rapidly and also returns quickly to the relaxed condition. Under such circum- stances the internal tension of the muscle remains the same during the course of the entire contraction, and for this reason the resulting curve is designated an isotonic myogram. The following details can be noted in an isotonic contraction-curve described by a muscle that has to lift only the light writing lever, and is not overweighted by any other attached weights: i. The stage of latent stimulation (Fig. 193, a b), which arises from the fact that the con- traction of the muscle does not begin at the moment of stimulation, but always somewhat later. If the momentary stimulus, for example an induction-shock, be applied directly to the entire muscle, the latent period is about o.oi second. In man the stage of latent stimulation varies from 0.004 to o.oi second. 36 562 ISOTONIC CONTRACTION CURVE. If provision is made in the experiment for the muscle to contract immediately, so that no time is lost between the act of the relaxed muscle becoming tense and the commencement of the contraction, the latent stage may fall below 0.004 second. For the excised frog's muscle, Bernstein and Engelmann found the shortest period to be 0.0048 second. If the animal's muscle remains attached to the body, protected as well as possible from external injuries and supplied with circu- lating blood, then the latent stimulation may be shortened to 0.0033 second, and even to 0.0025 second. Influences Affecting the Duration of the Latent Period. The latent period is diminished by increase in the strength of the stimulus and by heat, and increased by fatigue, cooling, and increase in the weight. The latent period of an opening contraction is also longer (even 0.04 second) than that of a closing contraction. Before the muscle contracts as a whole, individual muscle-elements within it must already have undergone contraction. It is, therefore, assumed that the latent period of the individual muscle-elements is shorter than that of the entire muscle. The latent period is shorter after direct muscle-stimulation than after indirect stimulation through the nerve, as the transference of the stimulus through the motor end-organ requires some time. The transmission of the nerve-stimulus is considered on p. 667. 2 . From the beginning of the contraction to the height of the short- ening (b d), the muscle contracts at first somewhat slowly, then more rapidly, and finally toward the end of the shortening more slowly again; so that the ascending limb of the curve has the form of an j . This is ./ termed the stage of increasing energy; it lasts about 0.03 or 0.04 second. FIG. 193. Myogram of an Isotonic Contraction. Its duration is the shorter the smaller the contraction (weaker stimulus), the smaller the weight to be raised, and the less fatigued the muscle. 3. After the height of contraction has been reached, the muscle again becomes extended, at first slowly, then more rapidly, and finally more slowly again ; so that the descending limb has the form of an inverted J . This is the stage of diminishing energy (d e) ; it is usually of shorter duration than that of increasing energy. 4. After the descending limb of the curve has been recorded, there fol- low several after-vibrations (from e to f), due to the elasticity of the muscle, and disappearing gradually. These constitute the stage of elastic after-vibrations. The latter are, however, regarded as factitious, and due to the after-vibrations of Helmholtz's apparatus. If the stimulus is applied to the motor nerve instead of the muscle, the contraction is the greater and lasts the longer the nearer to the spinal cord the nerve is stimulated. It has, until now, been assumed that the muscle is weighted only with the light writing lever that it has to raise in recording the curve. If, however, it be after-loaded, that is if additional weights be hung on the lever that, sup- ported during rest, must be lifted during contraction, then the commencement of the contraction is delayed as the after-loading is increased. This is due to the ACTION OF POISONS ON MUSCLE. 563 fact that the muscle, from the moment of stimulation on, must first accumulate so much contractile force as is necessary to raise the weight. The greater the weight the longer is the period of time that must elapse before the act of lifting begins. Finally, a degree of after-loading is reached at which it is no longer possible to raise the weight. This indicates the limit to which the lever-force may operate. If a muscle, during contraction, be subjected to a temporary increase in tension, it will be found that a short, quick, and considerable increase in tension immediately diminishes the contraction ; while a more prolonged and slow increase somewhat later increases the contraction. The temperature of the muscle also has some influence. The duration of the contractile force diminishes with increasing temperature, increasing with increase in weighting. The rapidity with which the contractile force develops increases with increasing temperature, diminishing with increased weighting. The height to which an unweighted muscle may lift a weight increases with its temperature. A frog's muscle, supplied with circulating blood, exhibits the greatest contraction in response to stimuli at o C. As the temperature rises, the extent of contraction diminishes progressively. If the muscle becomes fatigued as a result of repeated stimulation, the stage of latent stimulation becomes longer and the curve remains lower, because the contraction of the muscle is less; while the abscissa becomes longer, because the muscle contracts more slowly (Fig. 194, I). Cooling of a muscle has like effects. Also the muscles of the new-born behave in a similar manner. The con- traction-curve has a flat apex, and is considerably prolonged, especially in the descending limb. If the nerve of the muscle is stimulated by the closing or opening of a constant current, the muscular contraction corresponds exactly to that already described. If, however, the current is applied directly to the muscle itself, and is closed and opened, a certain degree of persistent contraction, though often but slight, takes place during the period of closure, so that the curve assumes the form shown in Fig. 194, IV, in which the current was closed at S and opened at O. According to Cash and Kronecker, the individual muscles have a special form of contraction-curve. Thus, the omohyoid of the tortoise contracts more rapidly than the pectoral. The flexors of the frog contract more quickly than the extensors. The muscles of tortoises, the adductors of mussels, the muscles of the bat, and the heart contract slowly. The muscles of flying insects contract with great rapidity, those of the fly 350 times, and of the bee 400 times in a second. There are, however, slowly contracting muscles among beetles also, for example in the water-beetle, hydrophilus. White muscle-fibers are more irritable, have a shorter latent period, and are more readily fatigued than red fibers ; their contraction -period is shorter. They are therefore more active, and the contraction -wave is propagated more rapidly in them. They also produce more acid and heat during their activity. The red fibers execute protracted, continuous movements; hence, moderate, physiological tetanus. They intermediate the adjustment of the muscular force to the resistance to be overcome. Red fibers, or those. rich in protoplasm, are further present, especially in the continuously active muscles respiratory, masticatory, ocular, and cardiac. The white fibers execute the rapid, single movements. Muscles that contain principally white fibers have a greater lifting capacity and a more marked absolute power in the single contraction, but they are inferior to the red muscles in tetanic contraction. The contraction-curves of a mixed muscle con- taining white and red fibers may exhibit two elevations in the ascending limb, the first being due to the contraction of the active white fibers, and the second to that of the more sluggish red fibers. These are observed especially after the action of veratrin on the muscle-substance. The nerves supplying the white and red muscles also exhibit differences in their irritability. Action of Poisons. Small doses of curare, as well as quinin and cocain, in- crease the size of the contractions induced by stimulation of the nerve; larger doses reduce the size to the point of complete paralysis. Suitable, small doses of veratrin likewise increase the size of the contractions, while the stage of re- laxation is conspicuously lengthened. Acids accelerate the relaxation. Veratrin, antiarin, and digitalin in large doses induce such changes in the muscle-substance that the contractions become greatly prolonged and similar to a continuous, tetanic contraction. In muscles poisoned with veratrin or strychnin, the latent stage of contraction is at first shortened, but later lengthened. The gastrocnemius of a frog will contract more rapidly if supplied with circulating blood containing sodium bicarbonate. Kunkel believes that the essential factor in the action of 564 THE DURATION OF A MUSCLE CONTRACTION. the muscle-poisons consists in their control of the imbibition of water by the muscle-substance. As the muscular contraction depends on imbibition, the form of contraction of the poisoned muscle will be influenced by the state of imbibition produced in it by the poison. The contraction-curves of unstriated muscles are similar to those of striated muscles, but the contraction takes place, after a latent period of as much as several seconds, visibly later and more slowly. The contraction in a preparation of a frog's stomach lasts 600 times as long as that of a striated muscle, and the latent stage amounts to 1.5 seconds. The curve ascends more steeply than it descends, and its apex is flattened. Warming increases the height of the curve, and shortens the latent period and the duration of contraction; above 39 C., however, the conditions are reversed. A muscle contracted as a result of stimulation returns to its original length only if a sufficient extending force is applied to it, as by weights suspended from it. Otherwise it will remain somewhat shortened for a considerable time, the resulting condition being designated contracture or contraction-remainder. This is especially well marked in muscles that have been previously subjected to strong, direct stimulation, or are greatly fatigued, or more strongly acid, or approaching FIG. 194. I, Contraction of a fatigued calf-muscle from the frog, recorded on a v: fork. Each dentation represents 0.01613 second; a b, latent irritation; b c, stage of increasing energy, c stage of diminishing energy. II, The most rapid writing movement of the right hand, recorded on the vibrating plate of a tuning-fork. Ill, The most rapid tetanic tremor-movement of the right forearm, recorded on the same plate. IV, Myographic curve on closing and opening a current applied to the muscle itself (after Wundt). a condition of rigor, or have been obtained from animals poisoned with veratrin. The phenomenon of contracture is also observed in man. In man, single twitching movements of the muscles may be executed with great rapidity. The determination of the time-relations of such movements may be made most simple by recording the movement in question upon the vibrating plate of the tuning-fork. Fig. 194, II, represents the most rapid movement that Landois could execute voluntarily with the right hand in writing the letters n n in succession. Each ascending and descending part of the movement comprises 3.5 vibrations (i = 0.01613 second) = 0.0564 second. In III the right arm was made to vibrate laterally to and fro on the tuning-fork plate in tetanic tremor; here the to-and-fro movement comprised from 2 to 2.5 vibrations from 0.0323 to 0.0403 second. v. Kries found that a simple muscular contraction excited by an induction- shock lasts longer than a single, momentary, voluntary movement. The direct registration of the muscular thickening during a single voluntary contraction shows that the contraction within the muscle lasts longer than the movement developed in the passive motor organ itself. This shorter duration of the resulting movement, which at first appears paradoxical, is due to the fact that, shortly after the primary voluntary muscular contraction, a contraction of antagonists takes place, and as a result a part of the intended movement is cut off. Even with the most rapid voluntary movements in man, v. Kries found that about THE EFFECT OF TWO SUCCESSIVE STIMULI. 565 four impulses in the muscle were effective, so that they really represented short tetanic contractions. Pathological. In the presence of secondary degeneration of the spinal cord following apoplexy, of atrophic muscles associated with ankylosed extremities, of muscular atrophy, of progressive ataxia, and of paralysis agitans of long standing, the latent period is increased. On the other hand, it is diminished in the presence of the contractures attending senile chorea and spastic tabes. The entire curve appears to be lengthened in cases of icterus and diabetes. In cases of cerebral hemiplegia in the stage of contracture the muscular contraction resembles the veratrin-curve, as it does likewise in cases of spastic spinal paralysis and amyo- trophic lateral sclerosis. In cases of pseudohypertrophy of the muscles, the as- cending limb is short and the descending limb greatly lengthened. In the presence of muscular atrophy following cerebral hemiplegia and tabes, the height of the curve is reduced, ascent and descent take place gradually, and the contraction of the atrophic muscle resembles that of a fatigued muscle. In cases of chorea the curve is short. The reaction of degeneration is described on p. 669. According to Goldscheider contraction takes place sluggishly also in conjunction with affec- tions of the nerves, without any change in the irritability of the muscles them- selves. In rare cases the observation has been made in man that spontaneous motor stimuli give rise to prolonged muscular contractions, followed by after- contractions (Thomsen's disease). The muscle-fibers of such patients are broad, the nuclei increased in number, and the fibrils hypertrophied ; it has been sug- gested that the white fibers are wanting. Fr. Schultze and others have observed a peculiar muscular undulation. If two momentary shocks be applied successively to the muscle in such a way that each would alone have induced a maximal contraction, that is the greatest possible contraction, the effect will vary in accordance with the time that elapses between the two shocks. If the second shock be applied after the muscle has already become relaxed from the contrac- tion of the first stimulus, then a second maximal contraction simply results. If, however, the muscle is still in a phase of contraction or re- laxation from the influence of the first stimulus, the second shock gives rise to a new maximal contraction from the phase of contraction existing at that time. If, finally, the second shock follows so quickly upon the first that both occur during the period of latent stimulation, only one maximal contraction results. If both stimuli are only of moderate strength, not sufficient to induce maximal contraction, a summation of the effects of both takes place. At whatever stage of contraction the muscle may be as a result of the first stimulus (Fig. 195, 7, 6), the second shock will have an effect (b c) as if the phase of contraction brought about by the first shock were the natural passive form of the muscle. Thus, under favorable conditions, the contraction may be even twice as large as that induced by the first stimulus alone. The most favorable condition is the application of the second stimulus ^V second after the first. The effects of both are also produced if the second shock is applied within the period of latent stimu- lation. The second contraction of a summated contraction reaches its height in a shorter period of time than the first contraction alone would have done. The time for b c (Fig. 195, /) is, thus, shorter than that for a b. If a series of shocks be applied to the muscle in rather rapid succession, the muscle will have no time to relax in the intervals. It, therefore, in accordance with the rapidity with which the stimuli follow one another, remains in a state of continuous, shock-like, tremulous contraction that is designated tetanus. The condition of tetanus, or rigid spasm, is, thus, not a state of continuous, uniform contraction, but a discontinuous 566 TETANUS. form of movement, resulting from accumulated contractions. If the stimuli succeed one another with only moderate rapidity, the separate shocks may still be recorded in the curve (//). If, however, the stimuli are applied in more rapid succession, the curve has an uninterrupted ap- pearance (///). As a single contraction takes place more slowly during fatigue, it is obvious that a fatigued muscle will be more readily thrown into tetanus by a smaller number of single stimuli than a fresh muscle. All movements of considerable duration excited in the human body are thus to be regarded as tetanic, for they are constituted of a series of single contractions in rapid succession. Accordingly, every movement, however steady, will on close observation be found to exhibit intermittent vibration, which reaches its climax in tremor and becomes so conspicuous in cases of paralysis agitans. The number of single impulses sent to the muscles of the body in the execution of voluntary movements varies considerably when the contractions are slow from 8 to 14 in a second, when the contractions are rapid from 1 8 to 20, the average being 12.5 in a second. Fig. 196, I, represents a myogram of the left flexor brevis pollicis and the abductor pollicis during a continuous contraction of moderate intensity, recorded on the vibrating plate of a tuning-fork. The wave-like eleva- tions indicate the separate impulses, each dentation being equal to 0.01613 second. II represents a similarly recorded curve made by the extensor digiti tertii. n FlG. 195. /, Two successive submaximal contractions. 77, A series of contractions induced by 12 induction- shocks in a second. 777 Marked tetanus induced by rapid shocks. By the summation of single stimuli, the muscle voluntarily excited slowly to contraction is gradually brought to the desired degree of shortening. It is cus- tomary to effect an exact adjustment of the extent of movement by the develop- ment of resistances through antagonistic muscles, as observations on lean, mus- cular persons show. The tetanic contraction that occurs under normal conditions in the intact body has also been shown to be composed of single, successive contractions, as secondary tetanus may result from it; the latter may be induced also from a muscle in a state of strychnin-tetanus. If a muscle be connected with a telephone whose wires are attached to two pins, one of which is inserted into the tendon and the other into the tissue of the muscle, a sound will be heard when the muscle is thrown into tetanus, indi- cating that periodic motor processes, that is, successive contractions, are taking place in the muscle. The sound is most distinct when the tetanizing Neef's hammer vibrates about fifty times a second. The rapidity with which the successive stimuli must follow one another in order to induce tetanic contraction varies for the different muscles of the body, as well as for those of different animals. In the case of the muscles of the frog 15 successive shocks in a second are required on an average to induce tetanus (in the hyoglossus muscle only 10, in the gastrocnemius 27 shocks). If the shocks are feeble, more than 20 in a second are required. The muscles of the tortoise are thrown into a state of tetanus by only 2 or 3 shocks in a second; the red muscles of the rabbit by 10, the white TETANUS. 567 muscles by more than 30, human muscles by from 8 to 12, the sluggish abductor minimi digiti of man by 6 shocks in a second. The muscles of birds are not thrown into a state of tetanus even by 70 shocks, and the muscles of insects not even by from 350 to 400 in a second. In the muscles of the crab's claw, rhythmic contractions or rhythmically interrupted tetanus (in the astacus and hydrophilus) are observed as a result of tetanic stimulation. O. Soltmann found that the white muscles of new-born rabbits are tetanized by 1 6 shocks in a second, and that the tetanus thus induced resembles that of fatigued adult muscles. This fact explains the readiness with which tetanus occurs in the new-born. Curarized muscles are at times thrown into a state of tetanic contraction by a momentary stimulus. The extent of shortening in a muscle in a state of tetanic contraction is, within certain limits, dependent upon the strength of the individual stimuli, and also upon their frequency. The steepness of the tetanus-curve increases with increase in the strength of the stimuli rather than with increase in the frequency of the individual stimuli. With feeble stimuli the muscle exhibits greater con- tinuity in its contraction; intensification of the stimuli then causes a greater discontinuity in the curve (tendency to clonic spasm) ; and if the intensity of the stimuli be still further increased the curve becomes again more nearly con- tinuous. The contracture that may remain after tetanus is the more marked the stronger and longer the stimulation and the weaker the muscle. The height of the contraction and that of tetanus are the same for an unweighted muscle. Only in the case of the weighted muscle is the height of the single contraction less FIG. 196. I, Fluctuations during a continuous contraction of the flexor brevis pollicis and the abductor pollicis. II, of the extensor digiti tertii. than that of the tetanic contraction. At times a stimulus applied immediately after tetanus has a greater effect than one applied before tetanus. The tetanized muscle cannot maintain the same degree of contraction in- definitely if the succession of shocks remains the same. On the contrary, it will lengthen somewhat as fatigue sets in, at first rapidly, but later more slowly. If the tetanizing stimulus is withdrawn, the muscle does not immediately regain its natural length, but a certain contraction-remainder persists for some time, especially after long-continued induction-shocks. Muscle may also enter into a state of permanent contraction, which has not been definitely determined to be due to fusion of single contractions ; for example the transient contraction induced by certain chemical agents (such as ammonia and others), the elevations attending idiomuscular contraction, and that induced by the passage of a constant current. If rapid, weak induction-shocks (more than 224 and 360, even as many as 5000 in a second for frogs' muscles) be applied to the muscle or its motor nerve, the tetanus may cease after the initial contraction. This occurs with the least frequency of stimulation when the nerve is cooled; the higher the temperature of the nerve the greater the frequency of stimulation that may still be effective in inducing a long-continued tetanus. This initial contraction is a short tetanus; increase in the strength of the current renders the tetanus continuous. On the other hand, Kronecker and Stirling, however, observed tetanus occur with more than 24,000 shocks in a second. According to these investigators, the upper limit of frequency for the muscle that will still cause tetanus appears to lie near the limit at which fluctua- tions in the current can no longer be appreciated, even with other rheoscopes. 568 ISOMETRIC MUSCULAR CONTRACTION. Isometric Muscular Activity. While the experiments discussed in the foregoing are concerned with the determination of the changes in the length of a muscle on stimulation and the movement of a weight sup- ported by it, Pick has investigated the changes that take place in the tension of a muscle under the influence of stimuli, when its length is kept constant. Pick designates this process the isometric muscular act. The following apparatus will serve to demonstrate the isometric muscular act (Fig. 197) : The angular frame R is provided at its base with a long writing- lever S (abbreviated in the illustration), which is movable at the hinge- joint p. The muscle M, suspended from above, is connected with the writing-lever near its point of attachment. A strong spiral spring F is connected with the other arm of the writing-lever, and during the activity of the muscle, permits only the slightest degree of shortening to take place. This, however, is sufficiently magnified by the great length of the lever. A momentary electric stimulus is applied to the muscle by means of two elec- trodes (r r), and the writing-lever records the isometric curve. The isometric . , x - - |>s contraction-curve is, X on the whole, similar to the isotonic curve, as a comparison of the curves in Fig. 197 will show. Nevertheless, the following differ- ences exist: (i) The contracting muscle attains its maximum tension in the isome- tric muscular act more rapidly than it attains its maximum shortening in the iso- tonic act. (2) The FIG. 197. Isometric Muscular Act. contracting muscle in the isometric act maintains the degree of highest tension somewhat longer, while in the isotonic act it recedes more rapidly from the highest degree of shortening. In the isometric muscular act in man, voluntary excitation gives rise to a higher degree of tension than electric stimulation. In the frog, the tension of the muscle in a state of tetanus is about twice as great as it is in a maximal con- traction; in human muscle it may be even ten times as great. During extension of the tetanized muscle, as during its contraction, equal degrees of tension cor- respond to smaller lengths. In the case of unstriated muscles, the entire curve is much shorter in the isometric act than during the isotonic act, and its form is almost symmetrical. RAPIDITY OF PROPAGATION OF MUSCULAR CONTRACTION. If a muscle of considerable length is stimulated at one extremity a contraction occurs at that point, and rapidly traverses in a wave-like manner the entire length of the muscle to its other extremity. The excitation is therefore communicated to each successive part of the muscle by virtue of a special conductive capacity on the part of the muscle to enter into a state of contraction. In the frog the wave of contraction has an average velocity of from 3 or 4 to 6 meters in a second, in the rabbit of from 4 to 5 meters, in the lobster of only i meter, in MUSCULAR WORK. 569 unstriated muscles and in the heart of only from 10 to 15 millimeters. These figures, however, apply only to excised muscles, for in the striated muscles of living human beings the rapidity of propagation is much greater, namely from 10 to 13 meters. Method. For the demonstration of this motor phenomenon, Aeby placed a writing-lever transversely across the origin of a muscle of considerable length and another across its insertion. Both were raised by the thickening resulting from the contraction of the respective parts of the muscle, and the movements were recorded one above the other on the drum of a kymograph. If one ex- tremity of the muscle is now stimulated, the contraction-wave that rapidly traverses the muscle lifts first the proximal and then the distal lever. As the velocity with which the drum revolves is known, the rapidity with which the contraction- wave is propagated through the portion of muscle under examination can readily be calculated from the distance between the elevations of the two levers. The time corresponding to the length of the abscissa of the curve in- scribed by each recording lever is equal to the duration of the contraction in that part of the muscle; according to Bernstein this is from 0.053 "to 0.098 second. By multiplying this value by the ascertained rapidity of propagation of the contraction-wave through the muscle, the wave- length of the contraction-wave is obtained; this equals from 206 to 380 millimeters. The rapidity and the height of the contraction-wave are diminished by cold, fatigue, gradual degeneration, and some poisons. On the other hand, the strength of the stimulus and the extent to which the muscle may be weighted have no influence on the rapidity of the wave. In ex- cised muscle the wave diminishes in size during its course through the muscle, but not in the muscles of a living human being or animal. The contraction-wave never passes from one fiber to an adjacent fiber; neither does it leap over an interposed tendon or a transverse tendinous septum. If a muscle of considerable length be stimulated locally at its middle, a contraction-wave is propagated from the point of stimulation toward both extremities, and in other respects possesses the properties pre- viously described. If two or more points in the muscle are stimulated at the same time, the wave-movement sets out from each, and one may even pass over another. If a stimulus be applied to the motor nerve of a muscle, it will be conducted to each muscle-fiber, whose contraction-wave must develop at the motor end-plate and be propagated thence in both directions along the fiber, which is only from 5 to 9 centimeters in length. In accord- ance with the obvious inequality in the length of the motor fibers from the nerve-trunk to the end-plates, the contraction will not commence at absolutely the same moment in all of the muscle-fibers, as the conduction through the motor nerves likewise occupies a certain amount of time. The difference, however, is so small that the muscle, stimulated through its nerve, appears to contract simultaneously as a whole. An absolutely simultaneous, momentary contraction of all of the fibers of a muscle can occur only if all are stimulated at the same time. MUSCULAR WORK. The muscles are most perfect machines not only because they utilize most completely the substances consumed in their activity, but be- 570 MUSCULAR WORK. cause they are distinguished from all machines of human construction by the fact that, as a result of repeated exercise, they become stronger, better developed, and capable of increased activity. According to the usual method of estimation, the amount of work performed by a muscle is equal to the product of the weight lifted (P) and the height to which it is lifted (s); hence, A = s P. From this it follows, first, that if the muscle is not at all weighted, therefore, if P equals o, then A must equal o ; that is, no work is performed if there is no weight- ing. Further, if the muscle is burdened with an excessively heavy weight so that it is no longer able to contract, therefore, s equals o, then, likewise, no work is performed. Between these two extremes the active muscle is able to execute work. Strictly speaking, the contracting muscle lifts, in addition to the suspended weight P, half of its own weight p, which should be added to P as % p; hence, A=(P + ip) S. With the strongest possible stimulation, or maximal stimulus, that is, a strength of stimulus that causes the maximum degree of contraction in the unweighted muscle, the work performed increases progressively with each contraction as the weight increases to a certain maximum. If, as the weight is increased, the muscle can raise it to a gradually dimin- ishing height, the amount of work diminishes progressively; and, finally, as already noted, it becomes o, when no elevation is effected. The following table will illustrate the work performed by a frog's muscle, according to Edward Weber: Weight Lifted, Height in Milli- Amount of Work Performed in Grams. meters. in Gram-millimeters. 5 27.6 138 i5 25.1 376 25 11.45 286 30 6.3 189 If the weight be increased at any given moment during the contraction of the muscle, more work can be performed, but only if the stimulus applied does not fall below a certain minimum. The duration of the contraction is longer. If a muscle has contracted as much as possible for the purpose of lifting a heavy weight, it can be made to perform still more work by gradually diminishing the weight. It contracts still further and performs additional new work by raising the diminished weight. If the amount of work performed by the muscle be diminished by raising the weight before the contraction to a part of the height to which it would have been lifted by the muscle stimulated to the maximum, then the muscle will raise the weight to a still higher level. The investigations concerning muscular work yield the following results : 1. The muscle is capable of lifting a greater weight the larger its transverse section, that is the more fibers it contains arranged side by side. 2. The muscle is capable of lifting a weight the higher the longer it is, that is the more muscle-fibers it contains arranged in succession. 3. The muscle is capable of lifting the greatest weight at the com- mencement of contraction; as the contraction progresses, it is capable of lifting only a progressively smaller weight, and near the maximum con- traction only a relatively light weight. 4. By the term absolute muscular energy is meant, according to Ed. Weber, the weight that the muscle stimulated to the maximum is no MUSCULAR WORK. 571 longer capable of raising while in its natural passive form, without being stretched by the weight at the moment of stimulation. In order to obtain a standard for the comparison of the absolute muscular energy in different muscles and also in different animals, an estimation is made of the absolute muscular force for one square centimeter of cross-section. The mean cross-section of a muscle is determined by dividing its volume by its length. The volume is equal to the absolute weight of the muscle in question divided by the specific gravity of muscle-substance (1058). Thus, the absolute muscular energy for one square centimeter of a frog's muscle is from 2.8 to 3 kilos; for one square centimeter of human muscle from 7 to 8 or even from 9 to 10 kilos. Analogous figures for crustaceans are from 1.8 to 3.2; for beetles from 3.4 to 6.9; for mussels from 4.5 to 12.4 kilos. The transverse section of the muscles tested in man is estimated from cadavers having the same constitution and muscular development as the person under observation. In conformity with proposition 3 it is evident that a muscle during contraction will develop the greater absolute muscular energy the more it is extended before contraction. 5. If a muscle in a state of tetanic contraction maintains a weight in an elevated position, it performs no work during the time, but only in the act of elevation. Nevertheless, the muscle in the state of tetanus requires continued stimuli, and it exhibits metabolic changes and fatigue. The transformation of its potential energy is applied to the generation of heat. When the maximal stimulus is applied, a muscle is not capable of lifting as heavy a weight at one contraction as when tetanic stimulation is applied. During tetanic stimulation, moreover, the muscle develops the greater energy (even as much as twice the ordinary) the more frequent the stimulation, as has been ob- served with increasing frequency up to 100 stimuli in a second. If only moderate stimuli that do not excite the maximal contraction are applied to the muscle two possibilities present themselves. If the feeble stimulus remains constant, while the weight changes, the amount of work performed follows the same law that is operative during maxi- mal stimulation. If the weight remains the same, while the strength of the stimulus varies, then, according to Pick, the height to which the weight is raised varies in direct proportion to the strength of the stimulus. The stimulus that sets a muscle into activity must, naturally, attain a certain strength before it becomes effective liminal intensity of the stimulus. This is independent of the weight attached to the muscle. With a minimal stimulus a small weight is raised to a higher level than a large one; but as the stimulus is increased, the contractions increase in greater proportion with a heavy weight. A contracting muscle is capable of performing considerably more work if the weight to be lifted is attached to an inert mass that acts like a fly-wheel, or if the weight is swung to a considerable height. Starke was able almost to quadruple the work corresponding to a maxi- mal contraction by a proper selection of materials for this purpose. Also the production of heat is increased under such conditions, although in much less degree, and it is much more quickly diminished on fatigue. If the resistance applied to prevent the movement of a limb whose muscles, strained to the utmost degree, be suddenly removed, the limb will, with the greatest energy and rapidity, assume the position brought about by the muscles. Such springing movements are observed especially in grasshoppers, leaping beetles, and cheese-mites. Under special conditions a muscle may perform considerable work through its increase in thickness. In the intact body the vessels of a muscle dilate during muscular contraction, 572 THE ELASTICITY OF PASSIVE AND ACTIVE MUSCLE. so that the amount of blood circulating through it is increased. Evidently the vasodilator nerve-fibers contained in the same nerve-trunks as the motor nerves are stimulated at the same time as the latter. In estimating the absolute muscular energy of single muscles or groups of muscles in man, close attention should always be paid to the physical relations, for example leverage, effects, direction of the traction, degree of shortening, and the like. The absolute energy of certain groups of muscles may practically be measured readily by means of the dynamometer. This is constructed in part on the principle of the spring-scales, upon which the pressure or pull of the muscles in question is allowed to act. Quetelet has determined statistically the strength of certain groups of muscles. The pressure of both hands in man equals 70 kilos. The pull amounts to double this weight. The strength of the hands of a woman is about one-third less. Further, a man can carry more than twice his own weight, a woman only half her weight ; boys are able to carry about one-third more than girls. In estimating the work done by man, not only the amount of work he is able to perform in any one moment should be taken into consideration, but also the number of times in succession he can perform this work. In accordance with practical experience, the mean value of the daily work performed by a man during eight hours' activity has been estimated at from 6.3 to 10 (at most from 10.5 to n) kilogrammeters in a second, hence a daily usefulness of 288,000 (in round numbers 300,000) kilogrammeters. The work performed by a horse in a second is assumed to be 75 kilogrammeters horse-power or dynamic horse. This average performance of work may, it is true, be temporarily increased, but, the organism then requires a prolonged rest after the work is done, so as not to suffer in health as a result of the overexertion. The amount of work performed in walking and in bicycling is discussed on p. 595. Some substances, when introduced into the body, impair and eventually abolish muscular activity; for example mercury, digitalin, helleborin, potassium- salts, apomorphin, and others. Others have been shown to increase the functional activity of muscular tissue; for example caffein. theobromin, veratrin, muscarin in small doses, glycogen, kreatin, and hypoxanthin; extract of meat likewise causes rapid recovery of the muscles after fatigue. Unstriated muscles are capable of performing a great amount of work, for example the uterus during labor, the craw of granivorous animals. The longitudinal musculature of the earth-worm is capable of raising more than 15 kilos, the frog's intestine of overcoming the pres- sure of a column of water of i meters. THE ELASTICITY OF PASSIVE AND ACTIVE MUSCLE. MYOTONOMETRY. Preliminary Physical Considerations. Every elastic body has its natural form, that is the outer form that it possesses when no external force (traction or pressure) operates upon it. Thus, the passive muscle also possesses a natural form, when no traction or pressure is exerted upon it. If traction in a longitudinal direction be made on a muscle its connected parts must be somewhat separated from one another, and the natural form will be stretched under the influence of the elastic energy. If the extending force be removed, the elastic body will return to its natural form. A body is said to be completely elastic if it returns entirely to its natural form after the tension ceases. By amount of elasticity (modulus) is meant the weight, expressed in kilograms, by which an elastic body having a cross-section of one square millimeter would be stretched the equivalent of its own length, provided it did not previously rupture, as, naturally, often it does. For passive muscle this equals 0.2734, for bone 2294, for tendon 1.6693, for nerves 1.0905, for the coats of the arteries 0.0726. The amount of elasticity of "passive muscle is, thus, small, as the latter yields readily to tractile force; hence its elasticity is not great. The coefficient of elasticity is that fraction of the length of an elastic body to which it is stretched by the unit of weight applied to it. This is large for muscle at rest. When the traction reaches a certain degree the elastic body finally ruptures. The carrying capacity of muscular tissue, THE ELASTICITY OF PASSIVE AND ACTIVE MUSCLE. 573 just short of the point of rupture, varies for youth, middle and advanced age approximately in the proportions 7 13 12. In the case of unorganized elastic bodies the amount of extension is always directly proportional to the extending weight. In that of organized bodies, therefore also of muscle, this is not the case, however, as with continued increase in weight in equal amount they are extended less and less in the further course of observation than at first. At the same time, they may for days or even weeks gradually undergo a still further increase in length after the primary extension, corresponding to the suspended weight, has been attained, if the same weight be continued. This is designated elastic after-effect. The elasticity of passive muscle is small but complete, and is com- parable to that of India rubber. The muscle can be greatly elongated by means of small weights. With the uniform addition of further units of weight, uniform extension, however, no longer takes place, but a slighter increase in length corresponds with equal increments of weight the greater the load. This phenomenon may also be expressed as follows : the amount of elasticity of passive muscle increases with its increased extension. Method. For the purpose of studying elasticity, the muscle is suspended free from a support provided with a scale, and the lower extremity is loaded successively with different weights placed in a small attached weighing-pan. The resulting elongation is measured in each instance. To construct a curve of elonga- tion, the units of weight added successively are taken as abscissas, and the lengths corresponding to each load as ordinates. The following is an example from the hyoglossus of the frog: Weight in Grams. 0-3 i-3 2-3 3-3 4-3 5-3 The curve of elongation is not a straight line, as in the case of unorganized bodies, but it resembles a hyperbola in form. The stretched muscle has a some- what diminished volume, as have the contracted and the rigid muscle. Muscles permitted to retain their connections in the living animal with their vessels and nerves are more extensible than excised muscles. Perfectly fresh muscles elongate at first proportionately to the weight if the increase in the latter be uniform and be kept within narrow limits, therefore like unor- ganized bodies. If the weights be heavy the observations are not made without consideration of the elastic after-effect. Dead, and especially rigid, muscle possesses a greater elasticity than fresh, living muscle; that is a greater weight is required to stretch the former than is needed to stretch the latter to the same length. On the other hand, the elas- ticity of dead muscle is less complete; that is, after being stretched, it regains its natural form only within narrow limits. In contradistinction from the elastic after-extension of muscle when weighted, after the tension has become constant, Blix recognizes an after-contraction of muscle, which comes into play after removal of the weight. Further, he dis- tinguishes an after-relaxation in muscle that has been stretched, its tension in- creasing with the increase in length, but diminishing when the length has become constant; and, finally, an after-tension in a previously stretched muscle, whose length is diminished, the previously low tension again increasing, when the length has become constant. In the intact body the muscles are already stretched to a slight extent, as indicated by the moderate retraction that usually takes place when the muscular insertion is detached. This slight degree of extension is of importance with the occurrence of contraction; as otherwise the muscle would first have to contract, without immediately entering into activity, before it could exert traction upon the bones. The elasticity of the muscles becomes evident on the contractions of Muscle-length in Millimeters. Elongation in Millimeters. Elongation in Percentages. 24.9 30.0 5-i 20 32.3 2-3 7 33-4 i.i 3 34-2 0.8 2 34-6 0.4 I 574 THE ELASTICITY OF PASSIVE AND ACTIVE MUSCLE. its antagonists. The position of a passive limb depends upon the resultant of the elastic traction of the various muscle-groups. The elasticity of active muscle is diminished as compared with that of passive muscle; that is it is lengthened by the same weight to a greater extent than is resting muscle. For this reason active muscle is softer, as can be demonstrated in an excised, contracted muscle. The appar- ently increased hardness of tense, contracted muscles is due only to their tension. When an active muscle becomes fatigued, its elasticity is still further diminished. During the latent period, in which the develop- ment of electrical phenomena and of heat points to metabolic activity in the muscle, no change in elasticity has as yet been demonstrated. Method. Ed. Weber made observations in the following manner. The hyo- glossus muscle of the frog was suspended vertically, and its length was measured in the passive state. The muscle was then tetanized by induction-shocks and again measured. Progressively increasing weights were then attached to it, in succession, and the amount of stretching of the passive and then the length FIG. 198. Blix's Elasticity Recorder. of the tetanized muscle (supporting the same weight) ascertained. The extent to which the active, weighted muscle contracted from the passive, weighted condition is termed the height of the lift. This becomes steadily less as the weight increases, until finally the heavily weighted, tetanized muscle can no longer con- tract; that is the height of the lift is zero. Indeed, if the weight be exceedingly heavy it may happen that the muscle, when stimulated, not only can contract no further, but it may even elongate. According to Wundt, however, the elas- ticity of the muscle does not change under such conditions. In these observations the length of the active, weighted muscle is equal to the length of the equally weighted, passive muscle, minus the height of the lift. Tracings of the length-curves recorded by passive or contracting muscle stretched by weights can be conveniently made by means of the apparatus of Blix, as shown in Fig. 198. The rectangular piece (A B C) is movable hori- zontally between two strips (R R). To the vertical portion of the former is attached the freely suspended muscle (m), which is connected with the writing- lever (S S), the latter being attached to the horizontal portion near C by means of a hinge- joint. The writing-lever is provided with a small movable rod (dd), from which a weight is suspended. When the rectangular piece (A B C) is moved in the direction of the arrow, the weighted rod (d d) more closely ap- proaches the muscle, which thus becomes constantly more and more heavily weighted. With the muscle at rest (m) the curve o a b c e is first recorded by means of the displacement described. Then a similar curve is recorded while the muscle THE ELASTICITY OF PASSIVE AND ACTIVE MUSCLE. 575 is tetanized (M) by electrical stimulation; and the curve h i k is thus traced. With the aid of the apparatus both the extension-curve with increasing weight and the contraction-curve with diminishing weight can be recorded. Both curves are necessarily analogous, except that their form is reversed. The elasticity of muscle may also be measured by its rate of oscillation when twisted about its longitudinal axis. Kaiser found that the elasticity of active muscle depends upon its length at the time. It is least when the muscle has the same length in the active as in the passive state. If shortening occurs in a muscle stretched by a weight, its elasticity is diminished, and this reaches its minimum when the muscle becomes of the same length as the passive, unweighted muscle. If the active muscle contracts still further, its elasticity increases. Under the influence of certain poisons the elasticity of the muscles is altered as a result of changes in the condition of the contractile substance. Potassium causes shortening of the muscle, with simultaneous increase in its elasticity. Digitalin causes elongation of the muscle, together with increased elasticity. Physostigmin also increases the elasticity, while veratrin diminishes it and inter- feres with its completeness. Tannic acid renders the muscles less extensible, but more elastic. Ligation of the vessels causes first a diminution, and later an increase in the elasticity. Separation of the nerves from the muscle results in a diminution of the elasticity. The influence of temperature on the extensibility is as follows: As the temperature increases from o to 30 the muscle elongates, as its extensibility increases. The increase in length is proportional to the load. At 34 contraction occurs as a result of the thermal stimulation; above 47 the muscle-proteid coagulates. Unstriated muscles possess an exceedingly small amount of elasticity; at the same time the elastic after-effect lasts much longer, and immediately follows the primary stretching. Fibrous connective tissue possesses the greatest elasticity, elastic tissue less, and unstriated muscular tissue the least. The elasticity of a complex organ, made up of these tissues, depends, accordingly, upon the relative abundance of these elements. As a result of his experiments Edward Weber has reached the following con- clusions as to the nature of the contractile energy of muscle. He assumes the existence of two states in muscular tissue the passive and the active. Each of these is characterized by a special natural form. The passive muscle possesses the longer, thinner form; the active muscle the shorter, thicker form. Both the active and the passive muscle tend to maintain their respective form. If, now, the passive muscle be thrown into activity, the passive form suddenly changes into the active form, by virtue of its elastic energy. It is this latter that is capable of performing the work of the muscle. Schwann has already alluded to the simi- larity between the energy of an active muscle and that of a long, elastic, tense spiral spring. Both are able to lift the greatest weight only from the form in which they are most stretched. The greater the shortening they have already undergone, the smaller is the weight that they are further able to raise. Observations on elasticity can also be made on the muscles of living human beings. Under such circumstances, however, not alone the simple physical law of elongation is to be taken into consideration, for the elongation at the same time causes in the muscle changes in its irritability and in the blood-supply, as well as direct or reflex stimuli, all of which must necessarily modify its extensi- bility. If the extremity of the foot in man be raised vertically by means of a cord passing over a pulley and having weights attached to it, the muscles of the calf will be stretched. Mosso and Benedicenti found that, as the weight increased, the muscles became longer at the same or at an increasing rate, if the weight were continuous and increasing. If, however, the muscle is completely released, before the new, heavier weight is applied, then the length of the stretched muscle diminishes as the weight is increased. Further, the curve of elongation exhibits individual differences; it exhibits fluctuations in association with the respiratory curves; it may exhibit after-extensions and after-contractions; it changes with frequent repetition, with heat and cold. Strong, sudden stretching, and previous voluntary contraction and fatigue likewise have an effect. Investi- gations of this sort are designated myotonometry. 576 HEAT-PRODUCTION IN ACTIVE MUSCLE. HEAT-PRODUCTION IN ACTIVE MUSCLE. Method. The increased temperature of a muscle during contraction may be determined either by means of delicate thermometers introduced between the muscles, or thermo-electrically. The passive muscle on the opposite side of the body, or the blood within a vein, will serve for purposes of comparison. As the resistance to conduction in metals (platinum wire, lead strips) is increased by heat, the observation may also be made in this way. After Bunzen, in 1805, had observed the development of heat during muscular activity, v. Helmholtz demonstrated in 1848 that also ex- cised frogs' muscles, tetanized for two or three minutes, exhibit a rise in temperature of from 0.14 to 0.18 C. R. Heidenhain even succeeded by thermo-electrical means in demonstrating an increase in temperature of from 0.001 to 0.005 C. for each individual contraction. A similar condition exists in the beating heart, whose temperature rises with each systole. The production of heat in the muscle exhibits a latent stage, which is, however, of shorter duration than the latent period of move- ment. A contraction of a frog's muscle, weighing one gram, will produce an amount of heat equal to about three microcalories, which will raise the temperature of three milligrams of water from o to i C. The following facts have been ascertained concerning heat -produc- tion: T . // bears a relation to the amount of work performed, (a) If the muscle during contraction carries a weight that during rest extends it again, it performs no work that is communicated externally. All of the transformed, chemical, potential energy is, therefore, converted into heat during this movement. Under these conditions the genera- tion of heat corresponds with the activity; that is it increases at first with the weight and the height of the lift to the maximum point , and then, as the weight is further increased, the generation of heat diminishes. The heat-maximum, however, is attained with a smaller weight than the maximum of work. (6) If the muscle at the height of its contraction is relieved of its weight, then it will have performed some active work communicated externally. Under such circumstances the amount of heat generated is less than in the previous case ; and, indeed, the amount of work performed and the lesser amount of heat evolved, are the same in accordance with the law of the conservation of energy. (c) If the same amount of work is performed in the one case by many small contractions, and in the other by fewer but larger contractions, the amount of heat generated is greater in the latter instance. This fact indicates that large contractions are attended with a relatively greater metabolism than smaller ones, and experience is in accordance with it. Thus, the ascent of a tower by steps with a high tread causes much more fatigue (that is requires more metabolism) than ascent by steps with a low tread. (d) If a weighted muscle executes single contractions in succession, by means of which it performs work, the amount of heat thus generated is greater than if it carries the weight constantly in tetanic contraction. The transition of the muscle into the shortened form thus develops a greater amount of heat than the maintenance of that form. Also sum- HEAT-PRODUCTION IN ACTIVE MUSCLE. 577 mated contractions are, accordingly, attended with the generation of a smaller amount of heat than corresponds to that developed by two single successive contractions. As the stimulus becomes stronger, heat-production increases, in the case of isometric contractions proportionately to the degree of tension; that of isotonic contractions at first more rapidly than the height of the lift, but with strong stimuli proportionately to the latter. Even if the height of the lift, the strength of the stimulus, and the tension of the contracting muscle remain the same during successive contractions, the muscle nevertheless generates more heat during the first than during the following contractions. The amount of heat generated also depends upon the character of the stimulus employed; thus, a muscle tetanized by slow shocks generates more heat than one contracted by rapid shocks. 2. The development of heat depends upon the tension of the muscle; it increases with increase in tension. If the muscle be prevented from con- tracting by fixation of its extremities, the maximum of heat-production takes place during stimulation, and the more quickly the more rapidly the stimuli succeed one another. Such a condition arises during tetanus, in which the violently contracted muscles mutually oppose each other. Therefore, a marked development of heat has been observed in con- nection with this disease. Dogs thrown into a state of continuous tetanus by electrical stimulation or by the induction of spasm die in consequence of elevation of their bodily temperature to a fatal height (44 or 45 C.). This large production of heat is attended with a con- siderable degree of acidity and the formation of alcoholic extractives in the muscular tissue. In the case of isometric tetanus the metabolism and heat-production increase more rapidly than the tension as the stimulus becomes stronger. The continuous maintenance of tension in the muscle on the one hand, as well as the contraction of the muscle with a small amount of work without considerable tension, never- theless requires only relatively little metabolism for the generation of heat, as compared with the work, which is essentially proportional to the consumption of combustible material. If the stimulated muscle be so fixed that it cannot con- tract, and if it then by releasing its lower extremity be permitted to contract and lift a weight, an additional amount of chemical potential energy will be trans- formed for the performance of this latter task. 3. Heat -production diminishes as fatigue increases, and it again in- creases during recovery. The muscle becomes fatigued earlier in its production of heat than in its performance of work. 4. In a muscle normally supplied with circulating blood the produc- tion of heat, and also the mechanical performance of work, takes place much more energetically than in a muscle whose circulation is inter- rupted. Recovery following fatigue also takes place under such con- ditions more rapidly and completely. The total amount of work and heat in a muscle must always be equivalent to the transformation of a corresponding amount of chemical potential energy. Of this the portion that is transformed into work will be the larger the greater the force that is opposed as a result of the contraction of the muscle. In the latter event this equals about one-fourth of the transformed potential energy. If the resistance be less, the work performed is a smaller fraction of the transformed potential energy. At a high temperature, therefore probably in the febrile state, muscle exhibits greater metabolism for the generation of increased amounts of heat, without increase in the work performed. In man, the production of heat in muscles made to contract by electrical stimulation can be appreciated through the skin. It was observed by Landois also when voluntary movements were executed. Venous blood flowing from a contracting muscle acquires a higher temperature than the arterial blood by as much as 0.6 C. as a result of energetic action. 37 578 THE MUSCLE-MURMUR. The statement made by some that a rise in temperature, amounting to about 3^ C., occurs also in a nerve in action is denied by others; but an increase in temperature does occur in a nerve in process of degeneration. 5. As the muscle is an elastic body, thermal phenomena will occur in it as a result of purely physical influences, as in inanimate, elastic bodies, such as India rubber. Thus, heat is set free on stretching living or dead muscle; and, conversely, the temperature of the muscle falls on elastic shortening. THE MUSCLE-MURMUR. If a contracted muscle be at the same time maintained in a state of tension by the application of resistance to it, a sound or murmur will be audible, arising from intermittent variations in tension within the muscle. Method. For purposes of observation, auscultation is practised either by means of the ear applied directly, or with the aid of a stethoscope, over a tetani- cally contracted muscle in another person. Some individuals are able to appre- ciate the murmurs of their own muscles of mastication on closing the external auditory canals, and pressing the jaws forcibly together. If one external auditory canal be closed, and into the other there be inserted a small rod from the end of which is suspended a tetanized, weighted frog's muscle, the sound of this isolated muscle can be readily heard. If the contracting muscle is attached to an elastic spring, whose rate of vibra- tion can be varied, and if the rate of vibration is determined that must be im- parted to the spring in order that it shall be energetically set into vibration by the sounding muscle, the rate of vibration of the muscle-sound can be readily deter- mined for each case after a few trials. A writing-style may be fastened to the tip of the vibrating spring, and record the vibrations upon a smoked surface. A muscle, thrown into contraction by the will, vibrates from 19.5 to 20 times a second. The deep tone corresponding to such a small number of vibra- tions is, however, not audible, but the first overtone, corresponding to twice this number, is heard. The sound has the same rate of vibration when the muscle is contracted in animals, by stimulation of the spinal cord, and also when the motor nerve of a muscle is irritated by chemical means. If, however, the motor center in the cerebral cortex be stimulated, the contracting muscle will generate a tone that is the higher the stronger the stimulus. If a tetanizing induced current be applied to the muscle (also in man), the rate of vibration of the muscular sound corresponds exactly with the rate of vibration of the spring-hammer in the induction-apparatus. The sound can, therefore, be raised or lowered by changing the tension of the spring. Loven found that the muscle-sound is relatively the strongest when the weakest current is employed that will induce tetanus. The sound will then have the vibration-rate of the next lower octave. As the current is increased in strength, the muscle-sound disappears, and with a strong current it reappears with the same rate of vibration as that of the interrupter of the induction-apparatus. If the induction-shocks are sent through the nerve, the sound is not so loud, but otherwise it is of the same vibratory duration. By means of rapid induction- shocks sounds have been produced up to 704 and 1000 vibrations in a second. The first sound of the heart is in part a muscle-sound. Landois, in 1873, first reported the observation that the rumbling murmurs emitted by many fish (Cottus, sea-scorpion) are due to the loud sounds generated by the spasmodically contracted muscles of the shoulder-girdle, and still fur- ther intensified by the resonance of their large oropharyngeal cavity sur- rounded by a firm bony framework. He found at that time that even a single induction-shock that excited the muscles was able to generate the muscle-sound. Herroun, Yeo, and Mac William also noted a like condition in the contracting mus- cles of man. It must, accordingly, be considered as doubtful whether the muscle- sound can be regarded as evidence that tetanus is made up of a series of fluctua- tions in the density of the muscle. According to Bernstein, the sound heard during contraction occurs in the latent period. Hence, the cause of the muscle-sound is not to be sought in a displacement of the mass of the muscle. FATIGUE OF MUSCLE. 579 which is stationary during the latent stage, but in molecular processes that are responsible also for the process of negative variation in the current. FATIGUE OF MUSCLE. The term fatigue is applied to that condition of diminished functional capacity in which the muscle is placed as a result of prolonged activity. This condition is recognized during life by a peculiar sensory perception localized in the muscles. In the intact body the fatigued muscle is capable of recovery, as is also the excised muscle to a slight degree. A muscle is more readily fatigued than its motor nerve. The cause of fatigue is the accumulation in the muscular tissue of the products of metabolism, fatigue-bodies, that are formed as a result of mus- cular activity. Among these products are : phosphoric acid, free or com- bined in acid salts; acid potassium phosphate; glycerin-phosphoric acid ( ?) ; and carbon dioxid. The accuracy of the foregoing explanation is indicated by the fact that the fatigued muscle becomes again more capa- ble of activity if the substances named are washed away by the passage of a normal solution (0.6 per cent.) of sodium chlorid or of a weak solu- tion of sodium carbonate through the blood-vessels of the muscle. The consumption of oxygen on the part of the active muscle also promotes fatigue; for the passage of arterial (but not venous) blood through the vessels removes the fatigue by replacing substances that have been con- sumed by the muscle. Conversely, a muscle that is capable of activity may be rapidly fatigued by the injection of dilute phosphoric acid, acid potassium phosphate, or dissolved meat-extract into its vessels. An animal may be fatigued also by the transfusion of blood from a com- pletely fatigued animal. A muscle fatigued by work absorbs less oxy- gen while in this condition, and it also generates only a small additional amount of acid and of carbon dioxid. The activity that gave rise to fatigue has thus induced considerable metabolic activity in the muscle. The fatigued muscle requires a stronger stimulus than the fresh muscle in order to perform the same amount of work, that is, to lift a weight the same distance. The fatigued muscle is no longer able to raise heavy weights; its absolute muscular energy is therefore diminished. If the muscle is loaded with the same weight throughout the experiment, and if the stimulus is a maximal one (strong induced opening shock), then, from one contraction to the other, the height of the lift steadily diminishes by a constant fraction of the shortening. The fatigue-trac- ing is, thus, a straight line. The more rapidly the contractions follow one another, the more marked is this diminution in the height of the lift, and conversely. The excised muscle becomes fatigued to the point of exhaustion after a certain number of contractions. Under such circumstances it is a matter of indifference whether the stimuli follow one another in rapid or in slow succession. Analogous conditions are also observed in connection with submaximal stimuli. The fatigued muscle requires, further, a longer period of time for its contraction, which, therefore, takes place more sluggishly. Finally, the period of latent stimulation is also lengthened in a state of fatigue. The fatigued muscle is said to be more extensible. If the muscle is loaded with a weight so heavy that it cannot be lifted at all when contraction takes place, the muscle, nevertheless, be- comes fatigued, and, indeed, in a still higher degree than if it were able 580 FATIGUE OF MUSCLE. to lift the weight. The metabolism and the formation of acid are, thus, greater in a stimulated muscle maintained in an extended position than in one that contracts when stimulated. If a muscle loaded with no weight is made to contract by stimulation, it becomes fatigued but gradually. If the muscle is weighted only during the contraction, but not during the extension, it tires more slowly than if it were continuously weighted; as it does also if it is required to lift its weight only in the course of its contraction, instead of raising it at once at the beginning of the contraction. The suspension of weights from a muscle that is con- tinually at rest does not cause fatigue. If the arteries of a warm-blooded animal are ligated, complete fatigue will result after from 120 to 240 contractions, in from two to four minutes, on irritation of the nerve. Direct irritation of the muscle, however, will still be able to excite an additional series of contractions. The fatigue-tracings in both cases are straight lines. If the circulation in the muscles of a warm-blooded animal be uninterrupted, the contractions first increase in height, and then diminish, to pursue a straight line on stimulation of the nerve. Accordingly, it is found in persons that have used their muscles to the point of fatigue that the muscles and their nerves respond more actively to galvanic and faradic stimulation in the beginning, but to a steadily diminishing degree in the further course of the work. Novi has demonstrated with greater detail the course of the contraction to the point of fatigue. According to him, the isolated muscle stimulated to the point of fatigue exhibits several phases in its action. The first phase exhibits a period in which the contractions occur rapidly and increase in size an indication that the repetition of the stimulus causes an increase in the irritability of the muscle. In the second phase, of longer duration, the rapidity of the contractions is maintained, but their height diminishes a sign that the irritability of the muscle is now decreasing. The third phase, again shorter, embraces contractions of slower course, the height remaining unchanged. In a fourth phase the con- tractions become still slower, but again increase in height. Finally the fifth phase exhibits uniform diminution in the height of the contractions and increase in their duration, until exhaustion occurs. Only this last phase corresponds to Kronecker's law. According to v. Kries a fatigued muscle tetanized in maximum degree behaves like a fresh muscle tetanized in submaximum degree. Both exhibit an incom- plete transition from the passive to the active state. Recovery from the condition of fatigue may be brought about by the passage of a constant galvanic current through the entire length of the muscle, likewise by the injection of fresh arterial blood into its vessels, or of small doses of veratrin. Relatively small amounts of sugar (30 grams) increase the muscular energy. Cocoa, coffee, tea, and other substances exert a stimulating influence on muscular activity. ^ Among the poisons, curare and the putrefaction-toxins (ptomains) cause the fatigue-curve to pursue an irregular course. A. Mosso and Maggiora made observations on living persons, by having a weight lifted by the flexors of the middle finger, with the arm in a fixed position. Mosso found that the muscle tires sooner when stimulated directly than when excited indirectly through its nerve. Only for medium weights is the fatigue-tracing a straight line; for smaller weights it is S~shaped, and for larger ones hyperbolic. If a tetanizing, electrical stimulus be continued until the muscular power is ex- hausted, there will still be left in the muscle a residue of energy that can be utilized by the will; and, conversely, a muscle finally exhausted by voluntary contractions can still perform some work when impelled by an electrical stimulus. If both forms of excitation be employed in immediate succession, they will exhaust the muscle completely. Mental exertion diminishes the muscular energy in a marked degree, as do likewise hunger and high temperature, especially in conjunction with marked humidity and diminution of atmospheric pressure; also local artificial elevation or diminution of the muscle-temperature. The strongest muscular con- MECHANISM OF THE BONES AND THEIR ATTACHMENTS. 581 traction induced by the will cannot be further increased by strong electrical stimulation of the motor nerve. On the other hand, if the motor nerve be stimu- lated so that a less powerful contraction results, the will is unable to strengthen this contraction. The work performed by a muscle already fatigued is much more exhausting than a greater amount of work performed when it has been rested. Anemia gives rise to symptoms similar to those of fatigue, up to the point of inability to contract; while an abundant supply of blood rapidly refreshes the muscle. Fatigue of the legs, as after marching, hastens fatigue in the arms. Long- continued watching and fasting favor fatigue. Massage exerts a favorable in- fluence on fatigued muscles. If a muscle be completely exhausted by voluntary movement, and if, never- theless, the will be allowed to act as if to excite a contraction, the muscle will actually begin to contract again after a period of rest, until it becomes again exhausted, and so on. Mosso and Brandis assume that involvement of the central nervous system, including the psychic centers, is, in part, to betaken into account in connection with fatigue in man. If a sensory stimulus be applied at the com- mencement of a voluntary contraction, the movement will be intensified and accelerated. Pathological. In rare cases a morbid increase in the liability to muscular fatigue (myasthenia) has been observed without muscular atrophy or sensory or reflex disturbances. MECHANISM OF THE BONES AND THEIR ATTACHMENTS. The bones exhibit in their spongy structure an internal architecture, consisting of lamellae arranged for pressure and traction exactly in accordance with those lines that would be constructed by graphic statics in the representation of the forces in weighted beams of the same form. This architecture is, therefore, so completely adapted to the function of bone that it combines the greatest capa- bility as a supporting apparatus with the least expenditure of material. The joints are covered with a layer of cartilage, which moderates, by means of its elasticity, the concussions communicated to the bones. The surface of the articular cartilage is smooth, and thus permits the articular extremities to move freely upon each other. At the outer boundary of the cartilage arises the capsule of the joint, which encloses the cartilaginous extremities like a sac. The inner surface of the capsule is lined by synovial membrane, which secretes the viscid, slippery synovial fluid, and this facilitates considerably the free movement of the surfaces. The outer surface of the capsule of the joint is covered with numer- ous fibrous bands, which act partly as fortifying and partly as restraining liga- ments. The bony processes also are included among the restraining contrivances, for example the coronoid process of the ulna, which permits the forearm to be flexed only to an acute angle; also the olecranon, which prevents hyperextension at the elbow-joint. The continuous apposition of the articular surfaces is made possible (i) by the adhesion of the smooth cartilaginous surfaces, covered with synovial fluid and sliding on each other; (2) by the external capsular ligament; and (3) by the elastic tension and the contraction of the muscles. The articular cavities must be regarded as cleft spaces, bounded by free con- nective-tissue surfaces, and unprovided with endothelium. The articular carti- lage and also the adjacent connective tissue are bare. The intima of the synovial membrane does not consist of endothelium, but of protoplasmic cells provided with processes, together with a fibrous interstitial substance. It is almost every- where separated from the articular cavity by a thin layer of fibrillar tissue. The synovial membrane is composed of delicate bundles of connective tissue intermixed with elastic fibers; it is provided on its inner surface in part with folds containing fatty tissue and in part with villi containing blood-vessels. The internal articular ligaments or cartilages are not lined by synovial membrane. The points of attachment of the synovial membrane to the bones are termed insertion-zones. The colorless, stringy, synovial fluid has an alkaline reaction and the compo- sition of transudates. In addition, it contains a substance resembling mucin, as well as albumin and traces of globulin, lecithin, cholesterin, fat, soaps, lutein, and also salts. Excessive movement diminishes its amount and increases its density and also the amount of mucin, but diminishes the amount of salts. With regard to the mode of movement, joints may be divided into the fol- lowing classes : 582 MECHANISM OF THE BONES AND THEIR ATTACHMENTS. 1. Joints with a Rotatory Movement about One Axis. (a) The hinge-joint or ginglymus. The one articular surface represents a section of a cylinder or cone, about one axis of which the other surface, with a corresponding concavity, moves on flexion or extension at the joint. Examples: the joints of the fingers and the toes. Strong lateral supporting ligaments are always present, to prevent lateral flexion of the joint. The screw-hinge joint is a modification of the hinge- joint. The humero-ulnar articulation belongs to this class. Strictly speaking, simple flexion and extension do not take place at the elbow-joint; but the ulna is rotated on the trochlea of the humerus like a nut on a bolt; on the right humerus the screw is wound to the right, and on the left humerus to the left. The ankle-joint also belongs to this class; the nut is the articular surface of the tibia; the right joint resembles a left-handed screw, the left joint the reverse. (6) The pivot- joint (rotatio) , with a cylindrical articular surface ; for example , the articulation between the atlas and the odontoid process of the axis, which represents the axis of rotation. The axis of rotation of the articulation at the elbow- joint for pronation and supination extends from the middle of the cotyloid cavity on the head of the radius to the styloid process of the ulna. Accessory joints for this pivot- joint are, above, the articulation between the articular cir- cumference of the head of the radius and the lesser sigmoid cavity of the ulna; and, below, the articulation between the head of the ulna and the sigmoid cavity of the radius. 2. Joints with a Rotatory Movement about Two Axes. (a) The joints exhibit in the two axes, which intersect at right angles, a curvature that is different in degree, but the same in direction: for example, the atlanto-occipital articulation, or the wrist-joint, in which both flexion and extension, as well as lateral inclination, are possible. (6) The joints have a surface of curvature that pursues a different direction in the two axes, which intersect at right angles. To this class belongs the saddle- joint, the surface of which is concave in the direction of the one axis, and convex in that of the other; for example, the' articulation between the tra- pezium and the metacarpal bone of the thumb. The principal movements, here are (i) flexion and extension, and (2) abduction and adduction. Further, move- ment is possible to a limited degree in all other directions, and a cone-shaped space can be circumscribed by the thumb. In this manner the saddle- joint re- sembles a limited arthrodial joint. 3. Joints with a Movement on a Spiral Articular Surface (Spiral Joints}. To this class belongs above all the knee-joint. The condyles of the femur, curved from before backward, exhibit, on sagittal section of their articular surface, a spiral the center of which lies toward the posterior portion of the condyle, and whose radius vector increases from behind downward and forward. The joint permits, first of all, extension and flexion. The strong lateral ligaments on both sides arise from the condyles of the femur, at a point corresponding to the center of the spiral, and are inserted on the head of the fibula and the internal condyle of the tibia respectively. When the knee-joint is strongly flexed, the lateral liga- ments are relaxed; they become tense as extension increases, and in complete extension they form tense bands, which ensure lateral fixation of the knee-joint. In accordance with the spiral form of the articular surface, flexion and extension do not occur about one axis, but the axis constantly shifts with the points of contact; the axis traverses a path that likewise is sp'iral. The greatest flexion and extension cover about 145. The anterior crucial ligament is made more tense during extension, and acts as a check-ligament for excessive extension; the posterior crucial ligament is made more tense during flexion, and is a check- ligament for excessive flexion. The movements of extension and flexion at the knee are, however, rendered more complex by the screw-like movement of the joint, with the result that the leg deviates outward during extreme extension. Accordingly, the thigh must be rotated outward during flexion, if the leg is fixed. Pronation and supination further are observed in the knee-joint, amounting to 41 in extreme flexion, but being entirely absent in extreme extension. They are due to rotation of the external condyle of the tibia about the internal condyle. In all positions of flexion the crucial ligaments exhibit a fairly uniform degree of tension, as a result of which the articular extremities are held in apposition. It is owing to their arrangement that with increase in the tension of the anterior ligament during extension the condyles of the femur must roll more on the anterior portion of the articular surface of the tibia; while with increase in the tension of the posterior ligament during flexion they must roll more on the posterior FUNCTION OF THE MUSCLES IN THE BODY. 583 portion. Braune and Fischer found in the course of their investigations that flexion at the knee-joint is attended with rotation of the tibia. The transition from a position of extension to one of flexion of 20 is attended with an internal rotation of 6. From this point further flexion is attended with an external rotation, which amounts to 6 at a flexion of 90. 4. Joints with Rotation about One Fixed Point. These are the freely movable ball-and-socket joints (arthrodia). Movement is possible about innumerable axes, all of which intersect at the point of rotation. The one articular surface has an approximately spherical shape, while the other has that of a hollow sphere. The shoulder- joint and the hip- joint are types of this articulation. Instead of the numerous axes, about which movement is possible, three may be substituted, intersecting at right angles in space. Therefore, these joints have also been designated tri-axial. The movements possible are : (i) pendulum-like movements in any desired plane; (2) rotation about the longitudinal axis of the extremity; (3) movements circumscribing the surface of a cone, the apex of which corre- sponds to the center of rotation of the joint, and whose surface is circumscribed by the extremity itself. Limited artkrodial joints are ball-and-socket joints with a more limited range of movement, and in which, moreover, rotation about the longitudinal axis is wanting; for example, the metacarpo-phalangeal joints. 5. Rigid joints (amphiarthrosis) are characterized by the fact that movement is possible in all directions, but is limited in extent, owing to short and unyielding external articular ligaments. The articular surfaces are usually of the same size, and are almost flat. Examples are afforded by the articulations of the carpal and tarsal bones with one another. With regard to the mechanical origin of the articular forms of two bones movable upon each other, it is to be noted that the articular extremity to which the muscles are inserted near the joint becomes the acetabulum; while that ex- tremity to which the muscles are inserted at a greater distance becomes the head. Symphyses, synchondroses, and syndesmoses represent the junction of bones without the formation of an articular cavity. They are movable in all directions, but only to an extremely limited extent. Physiologically, they are thus closely related to the amphiarthroses. Sutures unite bones without permitting any yielding. The physiological significance of sutures resides in the fact that the bones may grow at their mar- gins, so that distention of the cavity enclosed by the bones is possible. ARRANGEMENT AND FUNCTION OF THE MUSCLES IN THE BODY. The muscles form 45 per cent, of the total mass of the body. The musculature on the right side of the body is heavier than that on the left. If the muscles are considered with regard to their function from the mechanical standpoint, the following categories may be distin- guished : A. Muscles without Definite Origin and Insertion. T. The hollow muscles, enclosing spherical, oval, or irregular cavities, such as the urinary bladder, the seminal -vesicle, the gall-bladder, the uterus, the heart; or forming the walls of more or less cylindrical canals, such as the intestinal tract, the muscular ducts of glands, the ureters, the oviducts, the vasa deferentia, the blood-vessels, and the lymphatics. Under such circumstances the muscle-fibers frequently are arranged in several layers, for example in longitudinal, circular, and oblique direc- tions. During activity all of the layers contract to effect diminution in the size of the enclosed cavity. It is inadmissible to ascribe different individual mechanical effects to the various layers, for example to main- tain that the circular fibers of the intestine narrow the tube, while the longitudinal fibers dilate it. Both sets of fibers rather act together in diminishing the enclosed cavity, namely by narrowing and shortening it. If, however, the wall of a hollow organ is pushed or folded inward either 584 FUNCTION OF THE MUSCLES IN THE BODY. by pressure from without or by partial contraction of a number of circu- lar fibers, muscle-fibers that pass through the valley of the excavation to the surrounding borders may obliterate the depression by partial contraction, thus partially dilating the enclosed cavity, and converting the concave aspect of the depression into a smaller, plane one. The various layers are innervated from the same motor source, a fact that likewise supports the view of their homologous action. 2. The sphincters encircle an opening or a short canal, which is either narrowed or firmly closed by their action; for example the iris, orbicu- laris palpebrarum, orbicularis oris, sphincter pylori, sphincter ani, sphincter vulvae, sphincter urethrae. B. Muscles with Definite Origin and Insertion. 1. The origin is completely fixed when the muscle is in action. The course of the muscle-fibers to their insertion is such that during con- traction the insertion approaches the origin in a straight line; for ex- ample the attollens, attrahens, and retrahens auriculse, and the rhom- boids. In the case of some of these muscles, the insertion is lost in soft structures, which then follow the line of traction; for example the azygos uvulae, the elevator of the soft palate, most of the facial muscles arising from the bones and inserting into the skin, the styloglossus, stylophar- yngeus, and others. 2. Both Origin and Insertion are Movable. Under such circum- stances the movements of both points are inversely as the resistances that have to be overcome by the movement. In this connection it should be borne in mind that these resistances can often be voluntarily increased either at the origin or at the insertion. Thus, for example, the sterno-cleido-mastoid may act either as a depressor of the head, or, if the head be fixed, as an elevator of the chest ; the pectoralis minor may act either as an adductor and depressor of the shoulder or, if the shoulder be fixed, as an elevator of the third, fourth, and fifth ribs. 3. Some muscles with a fixed origin undergo a deviation from the straight line in the further course of their fibers or their tendons. This may be merely a slight curving, as in the occipito-frontal or the elevator of the upper eyelid; or it may be an angular deflection of the tendon around a firm prominence, so that the muscular traction is made in an entirely different direction, namely as if the muscle acted from this pro- cess directly on its insertion. Examples of the latter are the superior oblique muscle of the eyeball, the tensor tympani, tensor veli palatini, obturator internus. 4. Many muscles of the extremities act upon the long bones as upon levers: (a) The muscle may act upon a lever with a single arm, the insertion of the muscle and the weight being situated upon the same side of the point of support, or fulcrum, for example the biceps, the deltoid. The point of application of the force, under such circumstances, is often situated close to the fulcrum. By this means, the rapidity of the move- ment during contraction of the muscle is greatly increased at the ex- tremity of the arm of the lever; for example, in throwing, the hand may move at a rate exceeding 22 meters a second; but force is lost. This arrangement, however, has the advantage that with lesser contraction of the muscle its force is diminished less than it would be if the contrac- tion were more marked, (b) The muscles may act upon the bones as upon levers with two arms, the point of application of the force (muscu- lar insertion) being situated upon the other side of the fulcrum than the FUNCTION OF THE MUSCLES IN THE BODY. 585 point of application of the weight; for example the triceps, the muscles of the calf. In both instances the muscular force necessary to overcome a given resistance is calculated according to the laws of the lever. Equi- librium will be established when the static factors that is the product of the force in its vertical distance from the fulcrum are equal; or when the force and the weight are inversely proportional to their ver- tical distances from the fulcrum. In determining the amount of muscular force and the weight , especial attention should be given to the direction in which these act on the arms of the lever. Thus, it often happens that the direction that was perpen- dicular to the arm of the lever in a certain position may act obliquely upon it during movement. The static factor of a force or weight acting obliquely on the arm of the lever is obtained by multiplying the force by the perpendicular dropped from the fulcrum upon the line of direction in which the force is acting. I. 11 IK. p i p, V ft) I FIG. 199. Diagrammatic Representation of the Action of Muscles on the Bones. In Fig. 199, I, B x represents the humerus, and x Zthe radius; A y the direc- tion of traction of the biceps. If the biceps acted only in the rectangular position, as in holding horizontally a weight (P) attached to the forearm or the hand, then the force exerted by the biceps (A) could be determined by the formula A . y x = P . x Z; whence A = (P . x Z) : y x. It is evident that in the depressed position of the radius x C, the conditions are different; then the force of the biceps Aj = (P! . v x) : o x. In Fig. 199, II, T F represents the tibia, F the ankle-joint, M C the foot in the horizontal position. The force (a) of the calf -muscles necessary to neutral- ize a force p directed from below against the anterior extremity of the foot would be: a = (p . M F) : F C. If the position of the foot is changed to the direction R S, then the force of the calf-muscles a t = (pj . m F) : F c. From the foregoing the amount of force with which muscles that, like the coraco-brachialis, are stretched over the angle of a hinge-joint, act on the arms of their levers is also evident. Here also the static factor is equal to the force multiplied by the perpendicular dropped from the fulcrum upon the line of direction of the force. In Fig. 199, III, H E represents the humerus, E the elbow-joint, E R the radius, B R the coraco-brachialis muscle. The factor in this position is A . b E. 586 FUNCTION OF THE MUSCLES IN THE BODY. If the radius is raised to the position E R lf the factor is A . a E. It should, how- ever, be noted here also that B R t < B R; hence the absolute muscular energy must be less in the more flexed position, as every muscle is able to lift less weight with increasing contraction. What is thus lost in energy is made up in elongation of the arm of the lever. 5. Some muscles have a double motor effect, which they usually exe- cute combined; for example, the biceps muscle is a flexor and a supi- nator of the forearm. If one of these movements is prevented by other muscles, the muscle does not participate in the execution of the other movement. Examples. If the forearm be strongly pronated and then flexed, the biceps does not participate; or if the elbow be tensely extended, supination is effected by the supinator brevis alone, not by the biceps. The muscles of mastication furnish another example. The masseter raises the lower jaw and at the same time pulls it forward. If the depressed jaw, however, be kept drawn strongly backward, the masseter does not participate in the succeeding elevation of the jaw. The tem- poral muscle raises the jaw, and at the same time draws it backward. If the de- pressed jaw be raised when drawn forcibly forward, the temporal does not par- ticipate in its elevation. The muscles of this group execute this partial movement only on the strongest exertion, or when the position of the bones is specially in- fluenced by other mechanical factors. The flexors of the leg also exhibit interesting, analogous relations. A muscle connected with one joint as a rule causes in a neighboring joint a movement opposite to that to which it gives rise in the joint over which it passes. For example, the brachialis anticus causes, in addition to flexion at the elbow- joint, also backward extension at the shoulder- joint. 6. Diarticular or poly articular muscles are those that pass over two or more joints in their course from origin to insertion. In these muscles the tendons may deviate from a straight line in certain positions, for example the extensors and flexors of the fingers and toes in flexion of the latter ; or the direction remains constantly straight, for example the gastroc- nemius. The muscles of this group exhibit also the following interest- ing conditions: (a) The phenomenon of so-called active insufficiency. If the origin and insertion of a muscle are too closely approximated as a result of certain positions of the joints over which it passes, it may happen that the muscle is compelled to contract to such a degree before its action becomes effective that further active contraction is not possible beyond the point at which its effect may first become manifest. For example, when the knee is flexed at an acute angle, the gastrocnemius is no longer able to accomplish plantar flexion of the foot ; the traction on the Achil- les tendon is made by the soleus alone, (b) Passive insufficiency is exhibited by the polyarticular muscles under the following conditions: In certain positions of the joints a muscle may already be so stretched and made tense as from this position to limit certain movements of other muscles like a rigid restraining band. For example, the gastroc- nemius is too short to permit complete dorsal flexion of the foot when the knee is extended. The long flexors of the leg arising from the tuber- osity of the ischium are too short to permit complete extension at the knee-joint when the hip-joint is flexed at an acute angle. The extensor- tendons of the fingers are too short to permit complete flexion of the joints of the fingers when the wrist -joint is completely flexed. In the dependent upper extremity movement of the forearm at the elbow-joint is attended with a change in the position of the upper arm. The long head of the biceps tends to rotate the upper arm backward with the elbow-joint in a position between extension and flexion at a right GYMNASTIC EXERCISES AND THERAPEUTIC GYMNASTICS. 587 angle; with the elbow-joint in a position of greater flexion, however, the rotation is forward. A diarticular muscle when sufficiently contracted will move the bone situated between the two joints in the same manner as that on which it is inserted. This associated movement impairs the strength of the princi- pal movement; and, conversely, the latter is strongest when the former is inhibited. The muscles that effect this inhibition have been designated by H. E. Hering pseudo-antagonists. They take part involuntarily in every movement, in order to limit the associated movement. 7. Syner gists is the designation applied to those muscles that, collec- tively, serve to exercise a certain kind of movement; for example the flexors of the leg, the calf -muscles, and others. Also the abdominal muscles, including the diaphragm, in contracting to diminish the size of the abdominal cavity, as in the act of straining; also the inspiratory and the expiratory muscles may be regarded as synergists. The dif- ferent heads of a muscle, or the two bellies of a digastric muscle, may also be considered from this point of view. Antagonists, on the other hand, is the designation applied to those muscles that in contracting have an effect opposite to that of other muscles. Thus, flexors and extensors, pronators and supinators, ad- ductors and abductors, elevators and depressors, sphincters and dilators, inspirators and expirators, are antagonists. When it is desired to develop the action of a muscle in its full force, it is customary to place it involuntarily first in a state of greatest pos- sible extension, as it is from this condition that the muscle is really capable of developing the greatest amount of force. Conversely, in the execution of delicate movements, requiring the smallest possible amount of force, a position is chosen in which the muscle in question is already contracted to a considerable extent. All of the fascias of the body are attached to muscles, and are made tense by corresponding movements of the latter (tensors of fasciae). GYMNASTIC EXERCISES AND THERAPEUTIC GYMNASTICS. PATHOLOGICAL VARIATIONS IN THE MOTOR FUNCTIONS. Gymnastic exercises are of great importance in the development of muscular function and of strength, and they should be practised by both sexes from early youth. The systematic activity increases the size of the muscles, and renders them capable of doing more work; in addition, the bodily fat is consumed in greater degree. With the increase in the size of the muscles the amount of blood is in- creased, and at the same time the bones, tendons, and ligaments are rendered more resistent. As the circulation is greatly increased in active muscle, exercise causes a general improvement in the circulation and in cardiac activity. As a result a favorable influence is exerted on the movement of the fluids of the body in persons especially of sedentary habits, who suffer from stagnation of blood in the abdominal organs (hemorrhoids, etc.). As, further, active muscle consumes a good deal of oxygen and generates much carbon dioxid, respiration is thus actively stimulated by gymnastic exercises. The general increase of metabolism gives rise to the feeling of well-being and of vigor, limits abnormal irritability and the tendency to fatigue. The whole body becomes more solid, firmer, and of heavier specific gravity. Swedish therapeutic gymnastics are employed to strengthen systematically the muscles in persons suffering from weakness of certain muscles or muscle- groups, and in consequence not infrequently exhibiting deformities in the position of the skeleton. The movements of these muscles are practised especially, being opposed by suitable resistance, which should be overcome by the subject, or be opposed by him without overcoming them. 588 GYMNASTIC EXERCISES AND THERAPEUTIC GYMNASTICS. Kneading, pressing, and stroking the muscles (massage) also promote the circulation of blood through them. These procedures may, therefore, be applied with advantage to muscles that are so enfeebled by disease that independent, systematic training by exercises or gymnastics can no longer be successfully pur- sued. Derangement of normal movements may occur in the apparatus concerned in passive movements, namely the bones, joints, ligaments, and aponeuroses, or in apparatus concerned in active movements, namely the muscles with their ten- dons and motor nerves. Fractures, caries, and necrosis, and also inflammatory processes, which render movements of the bones painful, impair such movements or even render them wholly impossible. A similar result is caused by dislocations or inflammations of the joints, relaxation of the articular ligaments, or firm adhesions between the articular surfaces (ankylosis) or between the ligaments and soft parts surrounding the joint. Deviations from the normal function may further be caused by abnormal curvatures of the bones, enlargements (hyperostosis) , or outgrowths (exostosis). Among the abnormal positions of the skeletal parts that occur frequently are to be included curvature of the spinal column laterally (scoliosis) , backward (kypho- sis) , or forward (lordosis) . These also give rise to disturbances of the respiratory movements. In the lower extremities, which have to bear the weight of the body, genu valgum (knock-knee) develops, especially in flabby, tall, young persons engaged in trades requiring much standing. The opposite curvature of the legs, genu varum (bowlegs), is usually the result of rachitic disease. Flat-foot (pes valgus) is due to depression of the arch of the foot, which then no longer rests upon its three normal points of support. This condition is often due to the same causes as genu valgum. The ligaments of the small tarsal joints are stretched, and the longitudinal axis of the foot is usually directed outward in marked degree. The inner border of the foot is brought closer to the ground. Pains in the foot and the malleoli render walking and standing difficult. Club-foot (pes varus) is the condition in which the inner border of the foot is raised, and the point of the foot is turned upward and inward; it is caused by a fetal arrest of develop- ment. All children are born with a slight degree of this position. Pointed toe (pes equinus) is the condition in which the point of the foot touches the ground; pes calcaneus, that in which the heel touches the ground. Both are usually de- pendent upon contracture of the muscles causing these positions, or upon paralysis of their antagonists. Persistent absence of earthy salts from the food results in a deficiency of these in the skeleton; the bones become thin, transparent, and even flexible. Rickets in children and the identical lameness in young domestic animals are caused by the fact that the calcium-salts of the food cannot be absorbed, on account of persistent disturbances of digestion. Analogous disturbances of the motor functions develop if the fully developed bones subsequently lose their calcium-salts to the extent of one-third or one-half (halisteresis) , and thus become brittle and soft osteomalacia. A certain minor degree of fragility of the bones and halisteresis occurs in old age. With regard to pathological alterations in the muscles, it should first be pointed out that the normal nutrition of muscular tissue can only take place if a sufficient supply of sodium chlorid and of potassium-salts is provided in the food, as these are integral constituents of muscular tissue. Otherwise, the muscles atrophy, and their reconstruction is prevented. Under such conditions, further, the central nervous system and the digestive apparatus also suffer, and the animals perish. The extent to which the muscles suffer in a state of inanition is described on page 440. Muscles and bones that for any reason are thrown out of function also undergo atrophy. In the atrophic muscles associated with ankylosis there is often found an enormous proliferation of the muscle-corpuscles, occurring as an "atrophic proliferation" at the expense of the contractile substance. A certain degree of muscular atrophy takes place normally in old age. The great reduction (from 1000 to 350 grams) in the muscular structure of the uterus after parturition is especially noteworthy. This is due in part to the diminished vascularization of the organ. In cases of lead-poisoning the extensors and interossei especially undergo atrophy. Atrophy and degeneration of the muscles give rise to secondary shortening and thinning of the bones to which they are attached. Section and paralysis of the motor nerves cause inactivity and finally de- generation of the muscles. Inflammation, softening, and sclerosis of the ganglion- STANDING. 589 cells in the anterior horns or in the motor nuclei of the medulla oblongata also give rise to atrophy of the muscles connected with them. Spinal paralysis and acute bulbar palsy (paralysis of the medulla oblongata) thus have an acute onset, while progressive muscular atrophy and progressive bulbar paralysis pursue a chronic course. Under these conditions the muscles and their nerves become thin and wasted. The muscles exhibit many nuclei, their contractile substance is partly in a state of fatty degeneration, and later disappears altogether. The intramuscular connective tissue is increased, often also the interstitial fat. Ac- cording to Charcot, the central nerve-cells are also the trophic centers for the nerves arising from them and for the related muscles. According to Friedreich, however, progressive muscular atrophy is a primary disease of the muscles, a primary interstitial myositis resulting in atrophy and degeneration, the central nervous system becoming involved in the degenerative processes only secondarily ; just as after amputation of an extremity corresponding parts of the spinal cord degenerate secondarily. Finally, mention should be made of pseudo-hypertrophy or lipomatous mus- cular atrophy, in which the muscle-fibers are completely atrophied, in association with an abundant development of fat between the fibers, without, however, degeneration of the nerves or the spinal cord. The muscular substance may also undergo amyloid degeneration, the amyloid substance penetrating and infiltrating the tissue. At times atrophic muscles exhibit a deep brownish-red color, probably due to alteration of the muscle-pigment. Muscles constantly compelled to per- form a large amount of work, such as the heart-muscle, the bladder, the intestine, undergo hypertrophy. If the mechanism of the skeleton becomes altered, for example as a result of rigidity of a number of joints, the muscles adapt them- selves more or less completely to the altered mechanical conditions by changes in their growth, expenditure of energy, and manner of movement. SPECIAL MOVEMENTS. STANDING. Standing is the vertical position of equilibrium of the body, secured by muscular action, in which the line of gravitation that is a perpen- dicular dropped from the center of gravity of the body strikes the ground within the supporting area of the soles of both feet. Of the various posi- tions, that of "standing erect" will be analyzed here. In this position, muscular activity is exercised in two directions : ( i ) to fix the articulated body into an inflexible column (to "stiffen"); and (2) in case of a variation of the equilibrium to neutralize the disturbance by suitable muscular contractions. The following muscular activities are observed in standing: i. Fixation of the head on the vertebral column. The occiput may move in various directions on the atlas, whose two concave articular surfaces converge anteriorly. The act of nodding is the most readily performed. As the center of gravity of the head lies in front of the supporting points on the atlas, relaxation of the muscles, as in sleep or in death, causes the chin to fall upon the chest. The strong muscles of the neck, which pull from the spinal column upon the occiput, fix the head on the vertebral column. In addition to the nodding movement directly forward, a similar movement is also possible obliquely forward and to the side. Rotation of the head in the articulations of the atlas is possible only to an inappreciable extent around the sagittal axis, likewise around the vertical axis, the latter occurring only when the head is flexed. No special muscular activity is necessary to prevent these movements in standing. When the head is rotated to the side, the contralateral vertebral artery is compressed in the vertebral sulcus, while that on the same side is enabled to carry more blood. The chief rotatory movement of the head occurs about the vertical axis of 590 STANDING. the odontoid process of the axis. The articular surfaces on the pedicles of the first and second vertebrae are convex toward each other in the middle, becoming somewhat lower anteriorly and posteriorly. The head is, therefore, highest in the erect position; if it is rotated on the odontoid process, it undergoes a slight spiral movement downward. In this way distortion of the medulla is avoided when the head is strongly rotated. In standing, no muscular action is required to fix these vertebrae, as rotation cannot occur when the muscles of the neck and the flexors and extensors of the head are at rest. 2. The vertebral column requires fixation by muscles in those sec- tions where its mobility is the greatest ; these are the cervical and lumbar regions. Here fixation is secured by the numerous and strong muscles of the cervical vertebrae, especially those of the neck, and the lumbar mus- cles, especially the strong origins of the extensor dorsi communis, sup- ported by the quadratus lumborum. The least movable vertebras are those from the third to the sixth dorsal; the sacrum is completely immovable. For a definite length of the column the mo- bility depends upon the following factors: (a) The number and the thickness of the elastic intervertebral discs. These are most numerous in the cervical region, and are thickest in the lumbar region and relatively also in the lower cervical region. They permit movement in every direction. The intervertebral discs together form one-fourth the entire length of the spinal column. They are com- pressed somewhat by the weight of the body; hence, the body is longest in the morning and after recumbency of some duration. The smaller circumference of the bodies of the cervical vertebrae must be more favorable for their movement on the discs than is the greater size of the lower vertebrae. (6) The position of the processes also materially influences the mobility. The greatly depressed spines of the dorsal vertebras prevent hyperextension. The articular processes of the cervical vertebrae are so situated that their surfaces are directed obliquely from before and above backward and downward. By this means relatively free movement is rendered possible in rotation, lateral inclination, and flexion. In the dorsal region the articular surfaces of the superior articular processes are directed vertically and directly forward, while those of the inferior articular processes are directed directly backward; in the lumbar region the corresponding position is almost vertical and sagittal. In the act of bending backward as far as possible, the most movable points of the spinal column are the lower cervical vertebrae, from, the eleventh dorsal to the second lumbar vertebra, and the two lower lumbar vertebrae. 3. The center of gravity of the part of the body thus stiffened (the head and the trunk with the arms) is situated on the anterior border of the inferior surface of the eleventh dorsal vertebra. The perpendicular line dropped from the center of gravity passes behind a line joining both hip-joints. Hence, the trunk would fall backward at the hip-joints; but this is prevented by the ilio-femoral ligament, 14 mm. thick, stretched between the anterior inferior spine and the anterior intertrochanteric line, and also by the anterior tense layer of the fascia lata. As ligaments alone are never able to withstand continuous traction, they are mate- rially supported by the ilio-psoas muscle, which is inserted on the lesser trochanter, and also in part by the rectus femoris, whose origin extends upward over the acetabulum to the anterior inferior spine. A lateral movement of the hip-joint, in which one thigh would be abducted and the other adducted, is prevented especially by the large mass of the gluteal muscles, which fix the thigh on the pelvis posteriorly and lat- erally. When the thigh is extended, the ilio-femoral ligament also is able to prevent adduction, aided by the tense fascia lata. 4. The part of the body that has thus far been made rigid, including the head and the trunk, with the arms and the thighs, and whose center of gravity is situated somewhat lower and only to such a slight degree further STANDING. 591 forward that the line of gravity passes through the line connecting the posterior borders of the knee-joints, must now be fixed at the knee- joints. Falling backward is prevented by the strength of the quad- riceps femoris, supported by the tension of the fascia lata. Indirectly, the ilio-femoral ligament is believed also to aid in preventing falling backward, because in this act the thigh must be rotated outward, and this is prevented by the tension of the ligament named in the upright posi- tion. Lateral flexion at the knee-joint is impossible on account of the arrangement of the hinge -joint, strengthened by the strong lateral liga- ments of the knee. Rotation at the knee-joint is impossible in the ex- tended position. 5. The center of gravity of the entire body is situated 4.5 cm. in a vertical line below the promontory of the sacrum. A perpendicular dropped from this point strikes the ground a little in front of the line connecting both ankle-joints. The body would, therefore, fall forward at the latter joints. This is prevented by the muscles of the calf, aided by the muscles of the deep layer, namely the tibialis posticus, the flexors of the toes, and the peroneus longus and brevis. The following additional factors have also been considered worthy of mention : (a) As the longitudinal axes of the feet form an angle of 50 at the heels, falling forward can take place only if the feet have taken a position more nearly parallel to their longitudinal axes. (6) Falling forward is opposed also by the form of the articular surfaces of the foot, as under such circumstances the anterior, broader part of the astragalus would have to be pressed between the two condyles. This last factor is actually of little importance, as falling forward does not require such a marked change of position as would be necessary to bring this mechanism into play. 6. The tarsal and metatarsal bones, united by tense ligaments, form the arch of the foot. This touches the ground at three points, the tuber- osity of the os calcis, the head of the first metatarsal, and the head of the fifth metatarsal bone. Between the last two points, however, the heads of the other metatarsal bones also form points of support. .The weight of the body falls upon the highest point of the arch, the head of the as- tragalus. The arch of the foot is maintained only by ligaments. The toes are able materially to aid in balancing the body by means of their muscle-play. Standing erect causes more fatigue than walking. Braune and Fischer have recently distinguished the following varieties of station, for which, in contradistinction from the foregoing older exposition, a different form of muscular activity is required, (i) The "normal position" is characterized by the fact that the line of gravity passes downward through the lines connecting the central points of both hip- joints, knee-joints, and ankle- joints, and passes upward through the centers of gravity of the trunk and the head. Accordingly, the body need only be stiffened; no muscular activity at all is required to prevent falling forward or backward. (2) In the "comfortable position" the line of gravity strikes the ground in front of the line connecting the centers of both ankle-joints at a point corresponding approximately to the anterior border of the ankle-joint. Hence, muscular action is necessary to prevent falling forward at the ankle-joints. (3) In the "military position" the line of gravity falls in front of the knee-joints and ankle-joints, striking the ground at a point corresponding approximately to the middle of the sole. Hence, falling forward must be prevented at both joints, and this induces great fatigue on account of the considerable and continuous muscular exertion. The position of the center of gravity in the living person is determined as follows: The body is placed on a narrow board the length of the body. A balanc- ing edge is placed beneath the board, and first the upper and lower halves are balanced, then the right and left halves. Finally, the body is balanced when standing upright on a small 'board. The center of gravity is situated at the 592 SITTING, WALKING, RUNNING, JUMPING. intersection of the three planes, passing in each instance at right angles to and along the balanring edge. The center of gravity of individual parts of the body may be determined in a similar manner on sections of a frozen cadaver. Pathological. The security of firm station is recognized from the swaying of the body, which may be easily registered with the aid of a small rod placed verti- cally on the top of the head, the swaying being recorded by means of a pen or a brush on a surface stretched horizontally above the head. Disturbances of sensation, such as occurs in tabes and the like, cause marked swaying; as do also muscular weakness, tremor, fatigue, coldness of the feet, the action of an- esthetics on the soles of the feet. SITTING. Sitting is the position of equilibrium in which the body is supported on the tuberosities of the ischia, on which a to-and-fro rocking movement can take place, as upon the rockers of a rocking-horse. The head and the trunk together are made rigid so as to form an immovable column, as in standing. The essential purpose of sitting is to place the lower ex- tremities out of service from time to time, in order that their muscles may recover from fatigue. The following varieties of the sitting posture have been distinguished: i. The forward sitting posture, in which the line of gravity passes in front of the tuberosities. In this position the body is supported either against a firm object, for example by means of the arms on a table, or on the upper surface of the thigh, which is either held horizontally or is flexed to an acute angle at the hip by a support placed under the feet. 2. The backward sitting posture is characterized by the passage of the line of gravity behind the tuberosi- ties. Falling backward is prevented under such circumstances by the back of a chair (if the latter extends upward as far as the head the neck- muscles also may undergo relaxation during rest), or by the counter- weight of the legs, kept extended by muscular action. In the latter event the sacrum may serve as a further point of support, while the trunk is fixed on the thigh by the ilio-psoas and the rectus femoris, and the leg is kept extended by the extensor quadriceps. Usually the center of gravity is so situated that the heels form additional points of support. This latter sitting posture is naturally not adapted for resting the mus- cles of the lower extremities. 3. In the median sitting posture (sitting erect) the line of gravity passes between the tuberosities. The muscles of the lower extremities are relaxed ; the rigid trunk requires only slight muscular action to balance it, falling backward being prevented by the ilio-psoas and the rectus femoris, and falling forward by the lumbar portion of the strong dorsal muscles. Usually, the balancing of the head is sufficient to maintain equilibrium. WALKING, RUNNING, JUMPING. By walking is understood horizontal progression effected with the least possible muscular exertion by alternate activity of the two legs. Method. The brothers William and Edward Weber, in 1836, analyzed the various positions of the body during the movements of walking, running, and jumping, and recorded these positions in continuous series, which thus represent a true picture of all the successive phases of locomotion. Marey, in 1872, deter- mined the time-relations attending change of position by connecting the motor organs in man and animals with apparatus that registered by means of air-trans- ference. He also further developed Weber's original idea, and has recorded the various phases of movement in walking, running, and jumping, and in moving animals by means of complete series of instantaneous photographs taken by a camera working on the principle of the revolver. The duration of exposure in WALKING, RUNNING, JUMPING. 593 each instantaneous photograph equals T - ff V(j of a second. When placed in a stroboscope, these series reproduce the natural movements; and by projection with the aid of a kinematograph they may also be shown as "moving pictures." Figs. 201, 202, and 203 represent such series of instantaneous photographs ob- tained in the manner described. Braune and O. Fischer, between 1895 ano ^ I &99> introduced a new method of recording the motor process in walking by means of bilateral chronophotographic exposures on an extensive coordinating system. In the act of walking the legs are alternatively active. While one, the "supporting" or "active" leg, carries the body, the other, the "hang- ing," "swinging," or "passive" leg, is inactive. Thus, each leg in regu- lar alternation goes through an active and a passive phase. The motion of walking may be divided into the following acts : First Act (Fig. 200, 2). The active leg is vertical, slightly flexed at the knee, and supports alone the center of gravity of the body. The passive leg is fully extended, and touches the ground only with the tip of the great toe (z). This position of the legs corresponds to a right-angle triangle, in which the active leg and the ground form the two sides (catheti), and the passive leg the hypothenuse. FIG. 200. Phases of the Movement of Walking. The thick lines represent the active, the thin lines the passive leg: h, hip- joint; k a, knee-joint; / b, ankle-joint; c d, heel; m e, ball of the metatarso-phalangeal joint; z g, tip of the great toe. Second Act. To advance the trunk, the active leg tilts from its ver- tical position (cathetus) into an oblique position (3) inclined forward (hypothenuse). In order that the trunk may remain at the same height, it is necessary for the active leg to be lengthened. This is accomplished first by complete extension of the knee (3, 4, 5), then by elevation of the heel from the ground (4, 5), so that the foot rests on the ball formed by the heads of the metatarsal bone, and finally by elevation of the foot on the joint of the great toe (2, thin line). As both sections of the foot are successively raised from the ground, like the links of a measuring chain that is lifted from the ground ("unwound"), the elevation of the foot from the ground has also been termed "unwinding" of the foot. . During the extension and forward inclination of the active leg the tips of the toes of the passive leg have been compelled to leave the ground (3). While this leg now becomes slightly flexed at the knee for the pur- pose of shortening, it executes at the same time a "pendulum-like" movement (4, 5), by means of which its foot is moved just as far in front of the active foot as it was previously behind the latter. When it attains this position, the foot is placed flat upon the ground 38 594 WALKING, RUNNING, JUMPING. (i, 2, thick line). The center of gravity is transferred to this, the hence- forth active leg, which at the same time assumes a vertical position, somewhat flexed at the knee. The first act is now begun again. In walking, the trunk also exhibits some characteristic secondary movements : (i) It inclines each time toward the active leg, as a result of traction of the glu- teal muscles and the tensor vaginae femoris, with the object of transferring the center of gravity. In heavy, short persons with broad pelves this produces the "waddling" gait. (2) In order to overcome the resistance of the air, especially FIG. 201. Slow Walking, Photographed in Instantaneous Pictures (after Marey). Only the side direct toward the observer is represented. From the vertical position of the right active leg (7) the entire phase of the movement of this leg follows in six pictures (from / to VI); after VI the vertical position is again reached. The Arabic numerals denote the simultaneous corresponding positions of the left leg, thus i = /, 2 = 77, etc., so that, for example, during position IV of the right leg the left leg at the same time has the position 7. FIG. 202. Instantaneous Photographs of a Runner (after Marey). Ten pictures in a second; sents the distance traversed in meters. the base line repre- in rapid walking, the trunk is balanced at a forward inclination. (3) During the " pendulum. "-motion the trunk rotates slightly about the head of the active femur. This rotation is compensated, especially in rapid walking, by the arm on the same side as the oscillating leg swinging in the opposite direction; while that on the other side at the same time swings in the same direction as the oscil- lating leg. O. Fischer has accurately determined the movement of the center of gravity of the body. The external forces to be considered are the weight, the resistance of the ground, the friction on the latter, and the resistance of the air. The time-relations of walking are influenced by the following conditions: (i) The duration of the step. As the rapidity of the pendulum-motion depends upon WALKING, RUNNING, JUMPING. 595 the length of the leg, it is evident that each individual, in accordance with the length of his leg, has a certain natural time of oscillation, which especially in- fluences his accustomed rate of walking. In addition, however, the duration of the step depends upon the length of time during which both feet touch the ground simultaneously. Naturally, this can be increased voluntarily. With a "rapid pace" the period of time is zero; that is, at the same moment that the active leg is placed on the ground the passive leg is raised. (2) The length (or stretch) of the step, which amounts to six or seven decimeters on the average, must be the greater, the more the length of the hypothenuse of the passive leg exceeds the cathetus of the active leg. Hence, in the longest steps the active leg is markedly shortened by flexion at the knee, so that the trunk is carried at a lower level. Similarly, long legs are especially able to make greater steps. According to Marey, Carlet, and H. Vierordt the pendulum-movement of the passive leg cannot be regarded as a true pendulum-oscillation, because it possesses a more nearly uniform rapidity, owing to muscular action. During the pendulum- movement of the whole limb, the leg oscillates independently at the knee-joint, as is especially evident in women. According to Ed. and Wm. Weber the head of the femur of the passive leg is held in the acetabulum chiefly by air-pressure, so that no muscular activity is necessary to carry the whole extremity. If all the muscles and the joint-capsule be divided, the head still remains attached to the acetabulum. By pulling on the thigh the borders of the cartilaginous rim of the acetabulum are closely applied in a valve-like manner to the margin FIG. 203. Instantaneous Photographs of a High Jump (after Marey). The pictures partly overlap as soon as the velocity of the forward movement diminishes on the descent after the jump. In the upper, left-hand corner is a dial, the white radius of which has moved forward one division in one-twelfth of a second. The base line represents the distance traversed, in meters. of the cartilage on the head of the femur. According to the statements of the brothers Weber, the thigh is released from the acetabulum as soon as air is allowed to penetrate the articular cavity by perforating the bottom of the socket. The brothers Weber showed that in walking on level ground an appreciable amount of mechanical work is performed, as the weight of the body must be lifted several centimeters with every step. Marey and Demery estimated that the work performed by a person weighing 64 kilos, when walking slowly, is equal to six kilogrammeters in a second; when running rapidly, it amounts to 56 kilo- grammeters. The performance consists in raising the whole body and extremities, in imparting rapidity of motion to them, and in maintaining the center of gravity. According to Rziha the work performed in each second in walking slowly is 3.5 kilogrammeters, in walking at a medium gait 5.46, in walking rapidly 7.87, in a short run 21.87, in a brisk run 42.87, and in a fast run 87.50 kilogrammeters. A bicycle-rider going at the rate of two meters in a second, performs 1.12 kilogrammeters, at a four-meter pace 4.51 kilogrammeters, at a five-meter pace 7.05, and at a six-meter pace 10.15 kilogrammeters. The normal capability of 596 COMPARATIVE STUDY OF MOTION. a bicycle-rider is three and one-half minutes for each kilometer, or a rate of 4.73 meters a second, with a daily capability of from 90 to 100 kilometers. The normal capability of a workman is in this connection assumed by comparison to be 6.3 kilogrammeters a second. A bicycle-rider, going at an average rate, traverses the same distance in half the time and with half the expenditure of energy that a pedestrian requires. With the same metabolic consumption of muscular tissue, the exertion and the degree of fatigue are greater in walking than in cycling. In long-continued cycling, likewise in long marches, there is an increase in the consumption of energy for the successive units of distance covered; at a moderate pace this increase amounts to about 20 per cent. The pressure on the ground in walking is distributed in the following manner: The supporting leg always presses more firmly on the ground than the other; the longer the step the stronger the pressure. The heel attains the maximum pressure more rapidly than the point of the foot. The length of the step varies not inconsiderably even when a voluntary attempt is made to have the steps of equal length ; as do also the degree of spread- ing of the legs and the duration of the various phases of walking. Running (Fig. 202) differs from rapid walking in the fact that a mo- ment exists in which both legs are off the ground, so that the body hovers in the air. The active leg, in being forcibly extended from a more flexed position, must each time give the body the necessary impetus. In jumping (Fig. 203) the body is suddenly raised by the most rapid and powerful contraction possible of the muscles in the lower extremi- ties, care being taken at the same time to maintain the equilibrium by appropriate muscular action. Pathological. Variations in the walking movements depend primarily upon diseases of the bones, joints, ligaments, muscles, and tendons. Then the motor nerves must be taken into consideration, irritation and paralysis of which give rise to disturbances of the normal movements. The extent to which the sensory nerves and the reflex apparatus in the spinal cord influence the gait is pointed out on pages 716 and 728. H. Vierordt has applied the graphic method to the analysis of pathological varieties of gait. Among these are, for example, the spastic, the oscillating or zig-zag gait, the gait of tabes and that of paralysis agitans. Abasia and astasia are the terms applied by Blocq in 1888 to the inability to walk and stand, arising from cerebral affections (hysteria, hypochondria, violent emotions, imperative conceptions, vertigo), while all other movements, even those of the legs, can be executed with full force and coordination. COMPARATIVE STUDY OF MOTION. The absolute muscular energy in animals is not, generally speaking, appreciably different from that of man. The greater exhibitions of force encountered in the animal kingdom arise from the thickness and number of the muscles, as well as from differences in the arrangement of their leverage or in the means for the transference of force. Thus, for example, insects are" capable of exerting a great amount of force; some of them being able to drag 67 times their own weight, while a horse can scarcely drag its own weight. While further, for example, a man, by pressure on a dynamometer with one hand, overcomes a weight equal to 0.70 time his own body-weight, a dog by lifting his lower jaw can overcome a weight 8.3 times that of his body; a crab by closing its claw overcomes 28.5 times its weight; a mussel in closing its shell, 382 times its body-weight. Standing is made easier in quadrupeds by reason of the much greater sup- porting surface; the springing animals assume, besides, more of a sitting position, and often use the tail as an additional support (kangaroo, squirrel). Birds possess a mechanical arrangement by means of which, in perching, their toes are flexed; in this way they are able to retain their grasp on twigs when asleep. In the stork and the crane, prolonged standing on one leg is made easy by the fact that no muscular action is required to render the leg rigid; fixation is secured by a process of the tibia fitting into a depression on the articular surface of the femur. In walking, a gait can be distinguished in quadrupeds ; the four feet are moved COMPARATIVE STUDY OF MOTION. 597 at different times, and always diagonally one after the other; for example, in the horse, right fore, left hind; left fore, right hind. In trotting there is an accelera- tion of this gait, so that the legs are moved together diagonally at two different times, while the body is at the same time raised higher. In the interval between both hoof-beats the 'body is in the air half the time in ordinary trotting, longer in an extended trot. The gallop: When a (right) galloping horse moves horizontally through the air, the left hind foot comes down first. Shortly afterward the left fore foot and the right hind foot come down simultaneously; the right fore foot has not yet reached the ground, and is directed far forward. Up to this point the body has maintained its horizontal position. When, however, a few moments later, the left hind foot leaves the ground, it is at a higher level than the fore foot; at the same time, the right fore foot is also brought down and placed far forward; the right hind leg and the left fore leg are in extreme exten- sion. At the next moment these limbs also leave the ground, and the hind foot acquires such an ascendency over the fore foot that it comes to be situated much higher than the latter. The body, therefore, is thrown forward and downward until the right fore leg, which alone still touches the ground, contracts actively, and pushes the body forcibly from the ground. When this has occurred, the horse again soars in air with the body directed horizontally. In galloping the longitudinal axis of the horse's body is placed obliquely to the direction of the movement, forming an acute angle. In an extended gallop (carriere), which is really a continuous jumping motion, the right hind leg and the left fore leg, for example, do not reach the ground simultaneously, the former striking first. The rapidity of this movement in the horse is 82 feet a second. Most beasts of prey, hares, etc.. employ only the carriere for rapid movements. The amble is a modification of the gait that is peculiar to many animals, for example the camel, the giraffe, the elephant. It occurs also in dogs and in horses, but it is not a favorite gait with the latter. It consists in advancing both feet on the same side simultaneously or almost so. I.Iarey fastened compressible ampullae under the hoofs of the horse, connecting them with registering apparatus; and thus accurately recorded the time-relations of the various gaits. Muybridge, in 1872 , was the first to obtain series of instanta- neous photographs of running horses, which Schmidt-Mulheim placed together in the stroboscope. In snakes the progression of the body is secured by elevation and depression of the ribs in a manner resembling rowing. Swimming is an acquired art on the part of man. The specific gravity of the whole body is, on an average, somew r hat higher than that of river-water, though somewhat lower than that of sea-water. In the quiet dorsal decubitus, with only the mouth and the nose above the surface of the water, sinking can be prevented by slight downward pressing movements of the hands ; sometimes no movement at all may be necessary. In this position progression may be accom- plished by simple extension and adduction of the legs. The movement may be accelerated by oar-like strokes with the arms. Swimming on the abdomen is more difficult, because the head, being held above water, increases the specific weight of the body. The body is advanced and held above water by movements divided into the following three phases: First phase, horizontal rowing movement of the extended arms from before backward to the horizontal position (forward movement) ; second phase, downward pressure of the arms toward the depth, with subsequent adduction of the elbows to the bod}'' (elevation of the body) , together with a drawing up of the extended legs; third phase, forward thrust of the arms, in contact with each other, and at the same time extension and ad- duction of the legs obliquely backward and toward the depth, as a result of which both elevation of the body and forward progression are effected. Unduly rapid movements are exhausting and defeat their own purpose. Special attention should be paid to suitable respiratory movements. Many land mammals, whose bodies are specifically lighter than water, move through it with a walking motion, especially of the hind legs; at the same time the feet, being directed downward, assure the normal position of the body, as they are specifically the heaviest parts of the body. Those mammals that live much in the water, as well as reptiles and amphibia, possess webbed feet and a propelling tail partly resembling that of fish. Whales resemble fish in the external appearance of their bodies. Fish primarily make use of their tail as a motor organ, which is moved by 598 COMPARATIVE STUDY OF MOTION. the powerful lateral muscles. Usually the caudal fin is bent in two opposite directions above and below; in slight movements it is bent only in one direction. By sudden extension of the tail, the fish exerts a pressure against the water, and thrusts itself forward. Many fish, such as the salmon, can thus hurl them- selves up out of the water. The dorsal and anal fins maintain the vertical posi- tion. The pectoral and abdominal fins, corresponding to the extremities, effect the smaller movements, especially upward and downward; during sleep the ab- dominal fins are spread out. Most fish possess a swimming-bladder. This is wanting, however, in many cartilaginei (cyclostomi) , or is rudimentary, as in the shark. It either opens into the alimentary tract through the air-passage, or the latter is only a temporary structure that is later obliterated. The swimming- bladder is, in part, to be regarded as a respiratory organ with afferent and efferent vessels, while in part it serves for hydrostatic purposes. In the dipnoi the bladder is transformed into a lung. The body of swimming birds has a much lighter specific gravity than has water, while their feathers are lubricated by the coccygeal glands. They propel themselves forward with their webbed feet. Flying, in mammals, is confined to the bat and its allied species. The bones of the upper extremities, including the phalanges, are greatly lengthened. Be- tween the latter, as well as the hind limbs (except the feet) , is stretched a thin membrane, which also partially includes the tail. The flying movement of this membrane is effected by the powerful pectoral muscles, which arise in part from a ridge-like elevation of the sternum and the strong clavicles. The so-called flying lemurs, squirrels, and opossums have merely a duplication of the skin, stretched laterally between the larger bones of the extremities, and serving as a parachute in jumping. Man is unable to imitate flying movements successfully, for even though he were able to construct artificial wings, he would still lack the strength of the pectoral muscles that is necessary to effect elevation of the body. In birds the body specifically is exceedingly light. Large air-sacs extend from the lungs into the thoracic and abdominal cavities ; even the bones are connected with the lungs by special canals, so that all the spaces in the bones of the cranium, spinal column, bill, and extremities are filled with air instead of marrow. The upper extremities, transformed into wings, are supported by the powerful coracoid bone and the clavicles (furcula), the latter being fused in the middle. The wings are operated by the powerful pectoral muscles, which arise from the large crest of the sternum. In flying upward the wings are half closed, and are moved with the anterior border directed obliquely forward and upward. The plane of the wings, without offering resistance to the air, follows in the same direction as the edge of the wings. Then the latter are spread out in a large arc downward and backward, with their surfaces pressed downward. While the under surfaces of the wings press against the air from above and forward, downward and backward, the bird moves forward and upward. Birds can rise only against the wind, partly because the wind striking horizontally against their backs would press them down, and partly because it would disarrange their feathers. By means of a revolving photo- graphic camera, arranged in an apparatus resembling a musket, Marey obtained complete series of pictures of flying birds at which he directed the apparatus. Among invertebrates, all insects possess six legs. In addition some of them (butterflies, bees) have two pairs of wings on the second and third thoracic segments. In beetles and earwigs the first pair is merely a covering; in the strepsiptera it is entirely rudimentary. Conversely, in the flies the second pair of wings is reduced to small swinging bulbs. Lice, fleas, and bedbugs have no wings at all. All spiders have eight legs, the moths having six in their youth. In the centipedes the first three body-rings carry each one pair of legs, while all the rest have either one or two pairs. The crustaceans also possess numerous feet, as a rule, some of them undergoing peculiar transformations, for example in the river-crawfish into mandibles, claws, ambulatory feet, abdominal swimming feet and fin-foot. In the arthropods all of the muscles are inserted on the inner surface of the chitinous covering. The muscles themselves are highly developed and capable of a great amount of energy and rapidity of movement. Molluscs lack internal supporting organs, while external ones (shells) of simpler construction are present. The muscles, which are partly striated , form a musculo- cutaneous tube about the body that causes the changes in the form of the body. In mussels the strong single or double sphincter-muscle of the shells is noteworthy. In the pecten (scallops) this muscle effects a springing movement in the water VOICE AND SPEECH. 599 by rapidly bringing the shells together. The molluscs provided with shells possess strong retractors. In the worms likewise the integument forms with the muscles a musculo- cutaneous tube. The unstriated muscle-fibers pass either longitudinally only (round-worms) , or longitudinally and transversely (scratching worms) , or finally longitudinally, transversely and vertically through the body (flat-worms). Some worms possess muscular suckers, and others one or two pairs of motile stump- like feet. In round-worms the epidermal cells, and in some bristle-worms the intestinal epithelium, pass directly over into muscle-cells, both together being called "epithelio-muscular cells." In the echinoderms also the muscles are united with the integument; in the holothurians there is an external, continuous layer of circular fibers, beneath which is a longitudinal musculature, arranged in five separate bands. In the star-fish and the hair-stars special muscles move the limbs of the radiating parts of the body. The sea-urchin, surrounded by a firm lime-capsule, has special muscles that move its spines, and by means of which it is capable of locomotion. The ambulacral feet also aid in locomotion. In the celenterates the muscle-fibers are transformed sections of epithelial cells. Hence, there are present "epithelio-muscular cells," which are striated in the medusa, and unstriated in the anemone and hydroid polyp. The free epithelial part may be provided with cilia. In the medusa these elements lie partly on the umbrella and partly on the tentacles. Among the polyps, the actinia have a strong muscular base, and, in addition, longitudinal and circular fibers on the body and on the tentacles. In some polyps muscles also accompany the gastro- vascular apparatus. Among the protozoa, striated muscle-fibers have been found in some infusoria, for example in the pedicle of the vorticella; while, in addition, the movements are executed by the movable protoplasm of the body, or by voluntarily motile cilia. VOICE AND SPEECH. SCOPE OF THE VOICE. PRELIMINARY PHYSICAL CONSIDERATIONS CONCERNING THE PRODUCTION OF SOUND IN REED-APPARATUS. The current of expired air, and under certain circumstances also that of inspired air, can be employed to throw the tense true vocal bands of the larynx into regular vibration, as a result of which a sound is pro- duced. This is termed the human voice. The true vocal bands of the larynx are elastic, "membranous reeds." By "reeds" are meant elastic plates that almost completely fill the space (frame) in which they are spread out, leaving, however, a small space for their movement. If air be blown against the reeds from a tube below them (air-tube), they will yield at the mcment that the tension of the air overcomes the elastic tension of the reeds. In this way a considerable quantity of air suddenly escapes, its tension rapidly diminishes, and the reeds return to their former position, to repeat again the movement described. From the foregoing it results that 1. During the vibration of the reeds, alternate condensation and rarefaction of the air must take place. It is chiefly this that (as in the siren) produces the sound, not so much the reeds themselves. 2. The "air-tube," which conducts the air to the membranous reeds, consists in the human voice-apparatus of the lower section of the larynx, the trachea, and, below, the entire bronchial tree. The bellows is the thorax, diminished in size during expiration by muscles. 3. The air-passage above the reeds is called a "reinforcing tube," and consists of the upper section of the larynx, the pharynx, and also the oral and nasal cavities, which are arranged in two stories one above the other, and can be closed alternately. The pitch of the tone depends upon the following factors: (a) The length of the elastic plates. The pitch is inversely proportional to the length of the elastic plates; that is the fewer the units of length that enter into the elastic plates the more numerous will be the units of time (vibrations) entering into the tone produced. For this reason the pitch of the shorter vocal bands in children and in women is higher than that in adults and in men. (6) The pitch of the tone is, further, directly proportional to the square root 600 ARRANGEMENT OF THE LARYNX. of the elasticity of the elastic plates. In the case of membranous reeds, and also in that of silk, it is directly proportional to the square root of the extending weight, which in the larynx corresponds to the force of the tensor muscles. (c) In the case of membranous reeds a more powerful blast not only strengthens the tone by increasing the amplitude of vibration, but it also raises the pitch of the tone, because the greater amplitude of vibration increases the mean tension of the elastic membrane. Among physical influences the following further are to be noted: (d) The reinforcing tube, which is exceedingly variable in form, also resounds when the larynx is intonated ; its primary tone is mingled with the sound of the elastic reeds, and, thus, it is able to reinforce certain overtones of the latter. This subject will be discussed in greater detail in the section on voice-formation. The individual characteristics of the voice depend essentially upon the form of the reinforcing tube. In reed-instruments the pitch of the tones can undoubtedly be influenced by varying lengths of the reinforcing tube; but this is not taken into consideration in the case of the larynx. (e) During intonation of the reeds the strongest resonance takes place in the air- tube, as the latter contains compressed air. This causes the vocal resonance that is heard when the ear is applied to the chest-wall. Strong intonation may even cause an accompanying vibration of the thoracic wall. In weak individuals, and in cases of falsetto voice, the vocal resonance is exceedingly slight. (/) Narrowing or widening of the glottis has no effect on the pitch of the tone; but with the glottis wide open, disproportionately more air must pass through it, thus materially increasing the work of the thorax. ARRANGEMENT OF THE LARYNX. Cartilages and Ligaments of the Larynx. The fundamental framework of the larynx is formed by the cricoid cartilage, which is shaped like a seal-ring. The inferior cornu of the thyroid cartilage articulates with the cricoid in its postero- lateral region. This joint allows the plate of the thyroid cartilage to tilt forward, the inclination occurring as a rotatory movement about a horizontal axis connecting the two joints, the upper border of the cartilage moving forward and downward. The joints also permit a slight shifting of the thyroid cartilage on the cricoid upward and downward, forward and backward. The triangular, pyramidal arytenoid cartilages articulate on the upper border of the plate of the cricoid cartilage to one side of the median line, forming approximately a saddle-shaped joint with oval articular surfaces. The latter permit a double movement on the part of the arytenoids, namely rotation on their base about their vertical, some- what oblique, longitudinal axis, by which the vocal process directed forward is rotated outward and upward, and the muscular process directed outward and overlapping the border of the cricoid cartilage posteriorly is rotated inward and downward, or conversely. In addition, the arytenoid cartilages may be displaced somewhat inward or outward on their bases. The true vocal bands, or vocal ligaments, are composed principally of elastic fibers. They arise close together from about the middle of the internal angle of the thyroid cartilage, and are inserted on the vocal processes of the arytenoid cartilages directed forward. The "ventricles of Morgagni" allow free play for the vibrations of the bands, and separate them from the upper "false" bands, or ventricular ligaments, which are covered by a fold of mucous membrane. The latter take no part in phonation. Numerous mucous glands of the mucous mem- brane keep the vocal bands moist. In accordance with the functions of the laryngeal cartilages in connection with the voice-apparatus, C. Ludwig has called the cricoid the "foundation-carti- lage," the thyroid the "tension-cartilage," and the arytenoids the "position- cartilages." Owing to the oblique downward inclination of their under surfaces the vocal bands readily come together when the glottis is narrowed during inspiration (for example in sobbing) ; and if the glottis is already closed, inspiration makes this closure still firmer. The false vocal bands exhibit the opposite relation, for when in mutual contact they are readily separated during inspiration; while during expiration they readily close, owing to the inflation of the ventricles of Morgagni. Action of the Laryngeal Muscles. Dilatation of the glottis is effected by the posterior crico-arytenoid muscles. In drawing the muscular ARRANGEMENT OF THE LARYNX. 601 processes of the arytenoid cartilages backward, downward, and toward the median line (Fig. 208), these muscles cause the corresponding vocal processes (/, /) to separate and move upward (77, 77). A large isosceles triangle is thus formed between the vocal bands, and another between the inner borders of the arytenoid cartilages, having their bases in con- tact, so that the aperture assumes a rhomboidal form. Pathological. Paralysis of these muscles may cause intense inspiratory dyspnea, on account of the failure of the glottis to dilate. The voice remains unchanged. In a freshly excised larynx the dilators first lose their excitability. FIG. 204. Anterior View of the Larynx, with its Liga- ments and Muscular Insertions: O. h, hyoid bone; C. th., thyroid cartilage; Corp. trit., corpus triti- ceum; C. c., cricoid cartilage; C. tr., tracheal cartilages; Lig. thyr.-hyoid. med., median thyro- hyoid ligament; Lig. th.-h. Int., lateral thyrp-hyoid ligament; Lig. cric.-thyr. med., median crico-thy- roid ligament; Lig. eric, track., crico-tracheal liga- ment; M. sl.-h., sterno-hyoid muscle; M. th.- hyoid, thyro-hyoid muscle; M. st.-th., sterno-thy- roid muscle; M. cr.-lh., crico-thyroid muscle. FIG. 205. Posterior View of the Larynx, after Re- moval of the Muscles: , epiglottis with the cush- ion (IF); L. ar.-ep., ary-epiglottic ligament; M.m., mucous membrane; C. W., cartilage of Wrisberg; C. S., cartilages of Santorini; C. aryt., arytenoid cartilages; O. c., cricoid cartilage; P. m., mus- cular process of the arytenoid cartilage; L. cr. ar., crico-arytenoid ligament; C. s, superior cornu, C. i., inferior cornu of the thyroid cartilage; L. ce.- cr. p. i., postero-inferior kerato-cricoid ligament; C. tr., tracheal cartilages; P. m. tr., membranous portion of the trachea. Also in the presence of organic disease in the distribution of the recurrent nerve, the branch to the posterior crico-arytenoid muscle is the first to be paralyzed. Likewise, in cooling the exposed recurrent nerve, this branch is always the first to fail in its function. The constrictor of the entrance to the larynx is the transverse arytenoid muscle, which connects the two outer borders of the arytenoid carti- lages by transverse fibers throughout their length (Fig. 209). On the posterior surface of this muscle are situated the crossed bundles of the oblique arytenoid muscles (Fig. 206), which have a similar action. Pathological. Paralysis of these muscles renders the voice feeble and hoarse, as much air escapes between the arytenoid cartilages during phonation. 6O2 ARRANGEMENT OF THE LARYNX. The intimate approximation of the vocal bands is effected by bringing the vocal processes of the arytenoid cartilages close together. To this end the latter must be rotated inward and downward by a forward and upward movement on the part of the muscular processes affected through the vocal or internal thyro-arytenoid muscles. These muscles, which are applied to the elastic borders of the vocal bands, and in fact are embedded in their substance and whose fibers extend to the outer borders of the arytenoid cartilages, rotate the latter so that their vocal Corn Corn inf. FIG. 206. Posterior View of the Larynx, with the Muscles: E, epiglottis with the cushion (WO; C.-W., cartilages of Wrisberg; C.-S., cartilages of Santorini; Cart, eric., cricoid cartilage; Cornu sup., superior cornu, Cornu inf., inferior cornu of the thyroid cartilage; M. ar. tr', transverse aryte- noid muscle; Mm. ar. obi., oblique arytenoid mus- cles; M. cr. aryt. post., posterior crico-arytenoid muscle; Pars cart., cartilaginous portion of the trachea; Pars memo., membranous portion of the trachea. FIG. 207. Nerves of the Larynx: O. h., hyoid bone; C. th., thyroid cartilage; C. c., cricoid cartilage; Tr., trachea; M. th.-ar., thyro-arytenoid muscle; M. cr. ar. p. posterior crico-arytenoid muscle; M. cr. ar. 1., lateral crico-arytenoid muscle; M . cr. lh., crico-thyroid muscle; N. LAR. SUP. V., supe- rior laryngeal branch of the vagus; R. I., internal branch; R. E., external branch; N. L. R. V., recurrent laryngeal branch of the vagus; R. I. N. L. R., its internal branch; R. E. N. L. R., its ex- ternal branch. processes must move inward. The glottis between the vocal bands is thus narrowed to a slit, while a broad, triangular opening remains be- tween the bases of the arytenoid cartilages (Fig. 210). The lateral crico-arytenoid muscle is inserted into the anterior border of the articular surface of the arytenoid cartilage; hence, it can only draw the cartilage forward. Some investigators, however, believe that it also can effect a rotation of the arytenoid cartilage similar to that of the vocal or internal thyro-arytenoid muscle, with the difference that the vocal process are not brought so close together. Pathological. Paralysis of the muscles effecting approximation of the vocal bands results in loss of voice. ARRANGEMENT OF THE LARYNX. 603 The tension of the vocal bands is effected by the action of muscles in separating their two points of attachment from each other. To this end the thyroid cartilage is drawn forward and downward chiefly by the crico-thyroid muscles, the angle of this cartilage being at the same time somewhat enlarged. One can readily convince himself of this move- ment by feeling his own larynx during the emission of high tones. The same muscles also approximate the anterior arch of the cricoid cartilage to the inferior border of the thyroid cartilage ; and as a result the posterior plate of the cricoid cartilage undergoes a backward in- clination. At the same time the posterior crico-arytenoid muscles must draw both arytenoid cartilages somewhat backward, and hold them in that position. The tense vocal bands become longer and nar- rower. FIG. 208. Diagrammatic Horizontal Section through the Larynx: 7, /, Position of the arytenoid carti- lages during respiration, in horizontal section; from their anterior angles run the convergent vocal bands to the internal angle of the thyroid cartilage. The arrows indicate the direction of traction of the posterior crico-arytenoid muscles. //, //, Posi- tion of the arytenoid cartilages as a result of the action of these muscles. FIG. 209. Diagrammatic Horizontal Section through the Larynx, to Illustrate the Action of the Aryte- noid Muscle : /, /, Position of the arytenoid carti- lages during quiet respiration. The arrows indi- cate the direction of traction of the muscle. II, II, Positions of the arytenoid cartilages produced by the action of this muscle. The tension of the vocal bands is aided by the genio-hyoid and hyo-thyroid muscles, which together draw the hyoid bone, and thus indirectly the thyroid cartilage, upward and forward in the direction of the chin. According to Harless, Schech, Kiesselbach, Hooper, and others, the crico-thyroid muscle effects elevation of the arch of the cricoid cartilage toward the thyroid cartilage. In this way the plate of the cricoid cartilage is directed backward and downward, thus causing increased tension of the vocal bands. Pathological. Paralysis of the crico-thyroid muscles renders the voice harsh and deeper, on account of insufficient tension of the vocal bands. The tension thus induced is of itself by no means sufficient for pho- nation, for on the one hand the triangular aperture of the glottis between the arytenoid cartilages that would result from the isolated action of the internal thyro-arytenoid muscles must be closed. This is brought about by the transverse and oblique posterior arytenoid muscles. Then the vocal bands themselves, which, with the action of the crico-thyroid and posterior crico-arytenoid muscles, retain their concave border, so 604 ARRANGEMENT OF THE LARYNX. that the glottis between them appears as a space having the form of a myrtle leaf, must be fully stretched, so that the glottis assumes the shape of a linear slit (Fig. 214). This compensation likewise is brought about by the internal thyro-arytenoid muscle. It is this muscle, moreover, that effects those delicate gradations of tension in the vocal band itself that are necessary for the production of tones of slightly different pitch. It is especially adapted for this purpose, as it comes close to the edge of the vocal band and is firmly inserted into the elastic tissue of the latter. The contracting muscle in addition gives to the vibrating vocal band the resistance necessary for its vibrations. As some of the fibers of the vocal muscle terminate in the elastic tissue of the vocal band itself, they may impart increased tension to individual segments of the vocal band, as a result of which modifications in tone- formation are possible. It must, therefore, be assumed that the coarser variations in tension are caused by separation of the thyroid cartilage from the arytenoid cartilages, while the finer gradations of tension are induced by the vocal muscle. The usefulness of the elastic tissue in the vocal bands does not consist so much in its ex- tensibility, as in its property of shortening without forming folds or creases. Pathological. When these muscles are paralyzed the voice can be produced only by powerful blasts, as much air escapes through the glottis. At the same time the tones are deep and impure. Uni- lateral paralysis results in napping of the corresponding vocal band. Relaxation of the vocal bands occurs spontaneously when the stretching forces cease to act, the thyroid car- tilage drawn forward and the arytenoid cartilages fixed pos- teriorly returning to the posi- tion of rest in consequence of the elasticity that is peculiar to their arrangement. Relaxation of the vocal bands may result also from the action of the thyro-arytenoid and lateral crico-arytenoid muscles. From the foregoing it follows that tension of the vocal bands and narrowing of the glottis are necessary for phonation. The epiglottis, which becomes more erect with high tones and falls with low ones, has an influence on the timbre (clear or muffled) of the voice, but has no effect on the pitch. The mucous membrane of the larynx, as well as the submucosa, is rich in delicate, elastic networks of fibers. The submucosa is loose and yielding in the region of the entrance to the larynx and the ventricles of Morgagni, a fact that explains the enormous swelling that often occurs in connection with so-called edema of the glottis. A clear, even, limiting layer lies beneath the epithelium. The epithelium is stratified, cylindrical, and ciliated, interspersed with goblet-cells, except on the true vocal bands and the upper surface of the epiglottis, where a stratified, squamous epithelium covers the mucous membrane, which in this situa- FIG. 210. Diagrammatic Horizontal Section through the Larynx, to Illustrate the Action of the Internal Thyro- arytenoid Muscles in Narrowing the Glottis: //, //, Po- sition of the arytenoid cartilages during quiet respiration. The arrows indicate the direction of traction of the mus- cles. /, /, Position of the arytenoid cartilages brought about by action of these muscles. ARRANGEMENT OF THE LARYNX. 605 tion bears papillae. Racemose mucous glands are present in groups on the carti- lages of Wrisberg, the cushion of the epiglottis, and in the ventricles of Morgagni; and are scattered in the other situations, especially on the posterior wall of the larynx. The blood-vessels form a dense, capillary network under the limiting layer of the mucous membrane; beneath this are two more layers of vascular net- works. The lymphatics form a superficial, narrower network beneath the blood- capillaries, and a deeper, coarser network. The medullated nerves, which have B FIG. 211. -.4, Vertical section through the head and neck as far as the first dorsal vertebra: a shows the position of the laryngoscope in order to see the posterior part of the glottis, the arytenoid cartilages, the upper surface of the posterior laryngeal wall, etc.; b shows the position of the laryngoscope in order to obtain a view of the anterior angle of the glottis. B, Large (6) and small (a) laryngeal mirrors. ganglia on their branches, are numerous in the mucous membrane; their termina- tions are unknown. The cartilage is hyaline in the thyroid, the cricoid, and almost in the entire arytenoid cartilage, with a tendency to ossification. Fibro- cartilage is found toward the apex and the vocal process of the arytenoid cartilage, and also in all the remaining laryngeal cartilages. The larynx grows until about the sixth year, then rests, but rapidly increases in size again at puberty. 6o6 EXAMINATION OF THE LARYNX. EXAMINATION OF THE LARYNX. LARYNGOSCOPY. EXAMINATION OF THE EXCISED LARYNX. After Bozzini, in 1807, had given the first impulse toward illuminating and examining the internal cavities of the body by means of the mirror, and Babington, in 1829, had viewed the glottis in this way, the singing- teacher, Manuel Garcia, in 1854, made investigations, by means of the laryngoscopic mirror, on himself and other singers, concerning the movements of the vocal bands during respiration and phonation. Turck and Czermak rendered the greatest service in the applica- FIG. 212. Method of Making a Laryngoscopic Examination. tion of the laryngoscope to medical purposes, the latter being the first to use artificial light for illumination. Rhinoscopy was first attempted by Baumes in 1838, and was systematically developed by Czermak. The laryngoscope consists of a small mirror, attached to a handle at an angle (Fig. 211, B), the instrument being introduced with the mouth wide open and the tongue drawn out (Fig. 211, A). The position of the mirror must be changed in accordance with the region to be reflected ; and it may at times even be necessary to ele- vate the soft palate by means of the mirror (b) . The mirror receives the picture of the larynx in the direction of the dotted line, and reflects it at the same angle through the oral cavity to the eye of the observer, which has taken its position in the line of the reflected rays. The illumination of the larynx is ac- complished by collecting either sunlight or light from an artificial source in a concave mirror, and permitting the concentrated bun- dle of rays to fall on the laryngoscopic mirror held in the throat. The latter reflects the light against the larynx, which is thus illumi- nated. The observer looks in the same direc- tion as the rays of light, either under the edge of the illuminating mirror, or through a cen- tral perforation in the latter. The laryngoscope received an important improvement at the hands of Oertel, who showed how the movements of the vocal bands could be followed directly with the eye by means of rapidly intermittent illumination through the disc of a stroboscope (laryngo-stroboscope) . By replacing the eye by a photographic camera, Ssimanowsky was able to photograph the movements of the vocal bands in an artificial larynx. FIG. 213. The Laryngoscopic Image During Respiration. EXAMINATION OF THE LARYNX. 607 v. Ziemssen showed that long, thin electrodes could be introduced as far as the larynx under the guidance of the laryngoscope, and that the vocal bands could be stimulated to activity by irritation of the muscles. Rossbach succeeded in stimulating the muscles and nerves of the larynx externally through the skin. FIG. 214. Image of the Larynx when a Sound is Begun. FIG. 215. View of the Trachea as far as the Bifurca- tion. In this way physiological information may be gained, or therapeutic applications may be made to the parts. Autolaryngoscopy was first employed by Garcia, and then by Czermak espe- cially for the study of the movements of the larynx. If one introduce an illumi- nated laryngoscopic mirror into his own throat, while placing the mouth opposite a plane mirror, he may easily see the picture of his own larynx re- fleeted in the latter. The laryngoscopic picture (Fig. 213) exhibits the follow- ing details : L, the root of the tongue, from the middle of which the glosso-epiglottic ligament passes downward ; on each side of the latter are the so-called valleculae (V V). The epiglottis (E) appears as an arch, shaped like the upper lip; beneath it in quiet res- piration is seen the lancet- shaped chink of the glottis (R), and on either side the bright, yellowish vocal liga- ment (L. v.). This vocal band is from 6 to 8 mm. long in chil- dren, from 10 to 15 mm. long in women when relaxed, and from 1 5 to 20 mm. when tense. In men it measures from 15 to 20 mm. and from 20 to 25 mm. respectively. The whole chink of the glottis is 23 mm. long in men and 17 mm. in women; when the vocal bands are tense 27.5 and 20 mm. respectively. The width of the vocal bands varies from 2 to 5 millimeters. Ex- ternal to the vocal band is the entrance (rima vestibuli) to the sinus of Morgagni (S. M.), represented by a dark band. Still further outward, and on a higher plane, may be seen the fold of mucous membrane (plica FIG. 216. Position of the Laryngeal Mirror in the Practice of Rhinoscopy. 608 EXAMINATION OF THE LARYNX. .ventricularis) covering the false vocal band or the ventricular ligament (L. v. s.). On the lower, lip-shaped border of the entrance to the larynx may be distinguished the posterior lower notch of the ostium pharyn- geum laryngis (above P.); and on either side of this the apices of the car- tilages of Santorini (5. S.) are visible, resting on the apices of the aryten- oid cartilages; immediately behind is the adjacent pharyngeal wall (P.). In the ary-epiglottic ligaments (W . W.) are the cuneiform cartilages of Wrisberg, and finally, external to these, may be recognized the depres- sions of the sinus piriformes (5. p.). Special attention should be given to the condition of the glottis and the vocal bands during respiration and phonation. During quiet respira- tion the chink of the glottis (Fig. 213) appears as a lancet-shaped slit, which is wider during life than in the cadaver. If deep respirations are taken, the chink widens considerably (Fig. 215), and if the mirror is favorably placed, it may be possible to see the rings of the trachea, and even the bifurcation. When the voice is produced, the glottis closes each time to a narrow slit (Fig. 214). Appendix. Rhinoscopy. The nasal cavity has important relations to speech and to respiration. By the introduction of a mirror bent at an angle, with the reflecting surface directed upward, it is pos- sible gradually to survey a field such as is reproduced in Fig. 217. In the middle appears the nasal septum (5. .) , on either side the longitudinally oval choanae (CTt.), and further below the soft palate (P. m.} with the pendant uvula (/.) On the borders of the choanal openings may be recognized the posterior portions of the inferior (C. i.), middle (C. m.) and superior (C. s.} turbinated bones, with the corre- sponding nasal meatus beneath each one. Least distinct are the upper turbinated bone and the lower meatus. At the uppermost part a strip of the roof of the pharynx (O. R.) may yet be seen, with the more or less developed pharyngeal tonsil. This s !f te , r