R Reaming anb ICabor. ^ # LIBRARY f University of Illinois, f § CLASS. BOOK. VOLUME. § | .6.16 3 9b , | B Books are not to be taken from the Library. ^ § Accessions No..I3l5&S9. # Return this book on or before the Latest Date stamped below. Theft, mutilation, and underlining of books are reasons for disciplinary action and may result in dismissal from the University. University of Illinois Library M 20 26 ! OS? 367 L161— O-1096 THE URINE IN HEALTH AND DISEASE, AND URINARY ANALYSIS. THE URINE IN HEALTH AND DISEASE, URINARY ANALYSIS PHYSIOLOGICALLY AND PATHOLOGICALLY CONSIDERED. BY D. CAMPBELL BLACK, M.D., L.R.C.S. Edin., F.F.P. & S. Glas., PROFESSOR OF PHYSIOLOGY IN ANDERSON'S COLLEGE MEDICAL SCHOOL ; PHYSICIAN TO THE GLASGOW PUBLIC DISPENSARY (DEPARTMENT FOR KIDNEY AND URINARY DISEASES) ; FORMERLY SENIOR ASSISTANT-PHYSICIAN TO THE GLASGOW ROYAL INFIRMARY, ETC., ETC. PHILADELPHIA: LEA BROTHERS & 1 89 5. CO. PEEFACE. A large experience of medical students has impressed me with the conviction that the importance which they attach to the examination of the urine, so important in throwing light on many obscure phenomena of disease, is usually not such' as the subject merits. Nor are students altogether to blame ; they are rather to be sympathized with in the enormous amount of details, many of them totally irrelevant to the scientific practice of medicine and surgery, which are embraced in the short curriculum of study at their disposal, and which consequently render an accurate knowledge of them absolutely impossible. Withhrtecent years the department of urology has so developed as almost to constitute a distinct science. Many of its minutiae are devoid of practical bearing, and many of the constituents described as existing in the urine, not a few of which I believe to be manufactured in the so-called process of isolation, may be regarded as the curiosities of the chemist's laboratory. In the following pages I have aimed at conciseness and the treatment of the subject from the practical and clinical standpoint. I have endeavoured to incorporate the latest useful informa- tion, and I hope that the book may prove acceptable to such as are fully occupied in practice, and are without ready access to the extensive current and other literature of the subject. To my friend and colleague, Professor Eobertson Watson, I acknowledge my cordial obligations for his invaluable services in supervising the greater portion of the proofs. D. C. B. Glasgow, October, 1894. CONTENTS. PART I. CHAPTER I. ANATOMY AND PHYSIOLOGY OF THE KIDNEY. Pi Semeiology — Size of the Kidney — Weight of the Kidney — Base- ment Membrane or Stroma of the Kidney — The Malpighian Capsule — The Glomerulus — Circulation of Blood in the Kidney — The Renal Vein — Lymphatics of the Kidney — Nerves of the Kidney — Theories of Secretion of Urine — Relation between Urinary Secretion and Arterial Pressure — Transparency of Urine — Odour, Colour, Fluorescence, Temperature, Quantity of Urine — Hydrnria and Polyuria — Influence of Pathological States — Variation of Density and Solid Residue in Disease — Specific Gravity of Urine — Density of Urine — Estimation of Total Solids — Reaction of Normal Urine — Determination of the Degree of Acidity — Alkalinity of the Urine — Variations in Reaction of Urine — Chemical Composition- of the Urine — Toxicity of the Urine — Pathologi- cal Sediments and Concretions — Accidental Elements of the Urine — Reactions of Normal Urine and Significance - 1 PART II. CHAPTER II. NORMAL ELEMENTS OF THE URINE. History of Urea — Description — Physiological Conditions which modify the Amount of Urea — Chemistry — Artificial Pro- duction of Urea, etc.— Physical Properties — Combinations with Vlll CONTENTS. PAGE Acids — Extraction and Preparation of Urea — Quantitative Analysis of Urea — Process of Leconte — Process of Millon — Process of Liebig — Volumetric Analysis — Hypobromite Process — Pathological Significance — Uremia — Medicinal Agents which influence the Excretion of Urea — Therapeutic Indications ------- 42-70 URIC ACID. Natural State — Extraction and Preparation of Uric Acid — Pro- perties of Uric Acid — Urates — Acid Sodium Urate — Acid Potassium Urate — Acid Ammonium Urate — Acid Calcium Urate — Acid Magnesium Urate — Lithium Urate — Tests for Uric Acid — Quantitative Estimation of Uric Acid — Uric Acid in Albuminous Urine — Extraction of Uric Acid from Calculi and Sediments — Physiological Relations of Uric Acid — Pathology of Uric Acid — Therapeutic Indications - 70-83 HIPPURIC ACID. Extraction — Tests and Quantitative Analysis — Physiology and Pathology ------- 83-86 CREATINE AND CREATININE. Extraction — Tests — Quantitative Analysis — Physiology and Pathology ------- 86-90 XANTHINE AND HYPOXANTHINE. Xanthine — Hypoxanthine - - - - - 90, 91 OXALURIC ACID. Oxaluric Acid - - - - - - 91 ALLANTOINE. Extraction— Tests - - - - - - 91, 92 SUCCINIC ACID. Extraction— Tests - - - - - - 92, 93 BENZOIC ACID. Extraction - - - - - - - 93 OXALIC ACID. Oxalate of Lime — Detection and Isolation from Urine — Quantita- tive Analysis — Physiology and Pathology - - - 93-95 CONTENTS. ix VOLATILE ACIDS (PHENOLS). PAGE Phenic Acid — Detection in Urine — Hydroquinone — Pyrocatechin or Alkaptone — Indol - - - - - 96, 97 COLOURING MATTERS. Urobiline — Properties of Urobiline — Reaction — Pathology — Uro- chrome and Uroerythrine — Indican — Tests — Uroglaucine — Urrhodine ....... 97-101 PATHOLOGICAL SIGNIFICANCE OF URINE, As from Colour and Density .... 101, 102 TO ESTIMATE THE TOTAL NITROGEN OF THE URINE. Kjaldahl's Method ...... 102 CHAPTER III. NORMAL ELEMENTS OF THE URINE (continued). Inorganic Substances. — Chloride of Sodium — Qualitative and Quantitative Analysis— Pathological Significance — Sulphuric Acid and Sulphates — Analysis — Quantitative Analysis of Sulphuric Acid and of Sulphur — Pathological Significance — Phosphoric Acid and Phosphates — Phosphoglyceric Acid — Qualitative and Quantitative Analysis of Phosphoric Acid — Variations of Phosphoric Acid in Urine — Potash, Soda, Lime, and Magnesia — Qualitative and Quantitative Analysis — Ammonia, Iron, Nitric Acid, and Nitrates and Nitrites — Silica — Peroxide of Hydrogen — Gases in Urine 103-117 PART III. CHAPTER IV. ABNORMAL CONSTITUENTS OF THE URINE. Classification of Albumens — Properties of Albumen — Coagulation by Heat — Coagulation by Nitric Acid — Tests for Albumen — Fallacies in Heat Test — The Nitric Acid Test — Fallacies in X CONTENTS. PAGE Nitric Acid Test — Tanret's Reagent — Picric Acid Test — Ferrocyanide of Potassium Test — Nitro-prussiate of Soda Test — Sodium Tungstate Test — Spiegler's Test — Stutz's Test — Roch's Test — Jaworowski's Test — Other Tests for Albumen — Mixed Albuminuria — Relative Value and Delicacy of Various Albumen Tests — Quantitative Analysis — Process of Tanret and Troyes — Bodeker's Method — Process of Brandberg — Esbach's Process — Zahor's Method — Pathological Significance — Therapeutic Indications — Purulent Albuminous Urine 118-147 Globuline (Paraglobuline ; Fibrinoplastic Substance) : Quantita- tive Analysis — Process of Hammarstein— Pathological Sig- nificance -------- 147-150 Fibrine; Murine : Properties of Mucus— Analysis - - 150-151 Leucomaines and Ptomaines - - - - - 152 PEPTONES. Properties of Peptones — Analysis — Process of Hofmeister — Re- action with Tanrec's Solution — Reaction with Millon's Solution — Reaction with Tannin — Picric Acid Reaction — Pathological Significance — Hemi-albumose (Propeptone) — Properties — Analysis - - - - - - 152-154 Transitory Albuminuria : Pathological Significance - - 155-157 GLUCOSE (DIABETIC SUGAR). History — Chemistry of Sugar — Tests for Sugar in the Urine — Trommer's Reaction — Fallacies of Trommer's Test — Fehling's Reaction — Fallacies of Fehling's Test — Purdy's Method of Estimating Sugar in the Urine — Schmiedeberg's Solution — Crismer's Test — Bismuth Reaction of Bottger — Hoppe- Seyler's Reaction — Almen's Reaction— Indigo Reaction — Phenyl-Hydrazine Reaction — Agnosti's Reaction — Picric Acid Reaction — Fermentation Test— Specific Gravity of Diabetic Urine— Quantitative Analysis— Urine containing less than CONTENTS. xi PAGE 5 per cent. Sugar— Duhomme's Quantitative Analysis — Approximate Estimate of Sugar by Specific Gravity — Gerrard's Percentage Glycosometer — Optical Quantitative Analysis — Pathological Significance — Idiopathic Glycosuria — Thera- peutic Indications — Simulated Glycosuria - - 158-177 LEVULOSE, LACTOSE, INOSITE. Levulose — Lactose — Inosite ----- 177-179 CYSTINE. Characters and Properties — Analysis- - - - 179-180 TYROSINE AND LEUCINE. Properties — Pathological Significance — Leucine — Properties — Pathological Significance — Analysis - - - 180-182 ACETONE. History of Acetone — Properties — Chautard's Test — Orthonitro- benzaldehyde Reaction — Extraction of Acetone from Urine — Quantitative Analysis — Pathological Significance — Various Forms of Acetonuria ----- 183-187 MELANINE, DIVERSE ACIDS. Melanine — Diverse Acids - - - - - 187 BILE ELEMENTS. Bile Elements — Mucine of Bile — Biliary Pigments : Bilirubine, Biliverdine, Biliprasine, Bilifuscine, Bilihumine — Detection of Colouring Matter of Bile in Urine — Gmelin's Reaction — Analysis — Rosenbach's Modification of Gmelin's Test — Huppert's Reaction — Bile Acids : Choleic or Taurocholic Acid, Glycocholic Acid, Cholalic Acid — Reaction of Bile Acids (Pettenkofer's Reaction) -Cholesterine — Analysis — Pathological Significance - - - - 188-194 FATTY MATTER. Lipuria — Chyluria — Galacturia — Detection of Fat in the Urine — Pathological Significance - 195-196 Xll CONTENTS. TUBE-CASTS. TAGE Granular Cylinders — Granulo -Fatty Cylinders — Amyloid Casts or Cylinders— Hyaline Cylinders— Cylindroids (Pseudo-Cylin- ders) — Spermatic Cylinders — Epithelial Cylinders — Hemor- rhagic Casts — Pathological Significance and Diagnostic Value ....... 196-200 CHAPTER V. ABNORMAL CONSTITUENTS OF THE URINE (continued). Carbonate of Ammonia — Ammonio-Phosphate of Magnesia — Phosphate of Soda and Ammonia — Acid Ammonium Urate — Analysis of Ammonia Salts — Sulphuretted Hydrogen 201-203 ORGANIZED SUBSTANCES. Blood Corpuscles — Hematuria — Hemoglobinuria — Heller's Re- action — Guaiacum Reaction — Haemin Reaction — Lechine's Reaction — Microscopic Examination — Pathological Signifi- cance — Renal Hemorrhage — Spectrum Analysis — Leucocytes (Pus) — Day's Test for Pus — Mucus — Epithelial Cells — Sper- matozoa — Organisms found in Urine - - - 203-214 CHAPTER VI. SEDIMENTS. Examination of Sediments — Non-Oganized Sediments — Distinctive Characters — Sediments in Acid Urine — Sediments in Alkaline Urine — Uric Acid and Urates— Characters of Urates — Ammonium Urate — Uric Acid Sediments — Hippuric Acid — Oxalate of Lime — Triple Phosphates — Phosphate of Lime — Carbonate of Lime — Sulphate of Lime — Cystine — Xanthine — Tyrosine — Bilirubine — Uroglaucine, or Indigotine — Hema- toidine — Cholesterine ..... 215-225 CHAPTER VII. TO DETERMINE THE CHEMICAL COMPOSITION OF A CALCULUS .... - 226-229 CONTENTS. xiii CHAPTER VIII. MEDICAMENTS AND ACCIDENTAL ELEMENTS IN THE URINE. PAGE Alcohol — Antipyrine — Antifebrtne, or Acetanilide — Arsenic and Antimony — Alkaloids — Aristol — Bromides — Carbolic Acid — Chloroform — Chloral— Chlorate of Potash — Iron — Iodides — Iodoform — Kairine — Lithia — Lead and Copper — Mercury — Naphthaline — Naphthol and other Phenols — Bethol — Phenacetine — Salicylates — Salol — Saccharine — Strontium — Tannin — Turpentine — Rhubarb — Santonine — Thalline — Urethan — Filaments of Tissues ; Grains of Starch - 230-239 Appendix ------- 240, 241 Index ------- 242-246 THE URINE IN HEALTH AND DISEASE AND URINARY ANALYSIS PART I. CHAPTER I. ANATOMY AND PHYSIOLOGY OF THE KIDNEY. Semeiology — Size of the Kidney — Weight of the Kidney — Basement Membrane or Stroma of the Kidney— The Malpighian Capsule — The Glomerulus — Circulation of Blood in the Kidney — The Renal Vein — Lymphatics of the Kidney — Nerves of the Kidney — Theories of Secretion of Urine — Relation between Urinary Secretion and Arterial Pressure — Transparency of Urine — Odour, Colour, Fluor- escence, Temperature, Quantity of Urine — Hydruria and Polyuria — Influence of Pathological States —Variation of Density and Solid Residue in Disease— Specific Gravity of Urine — Density of Urine — Estimation of Total Solids — Reaction of Normal Urine — Deter- mination of the Degree of Acidity — Alkalinity of Urine — Variation? in Reaction of Urine— Chemical Composition of the Urine —Toxicity of the Urine— Pathological Sediments and Concretions — Accidental Elements of the Urine — Reactions of Normal Urine and Signifi- cance. By the department of medicine termed semeiology (arjuElov, a sign) is understood that which treats of the signs of disease as illustrating and explaining the nature of the departure from health with which these signs are associated, and of which they are the evidences. In this there is of necessity implied a know- ledge of the healthy functions and a valid process of deductive 1 2 THE URINE IN HEALTH AND DISEASE. reasoning. The functions of the kidney, and the significance attached to the modifications and varieties of its secretion and excretion as bearing upon disease and indicating rational treatment, have engaged attention from the birth of medicine as a science. Two organs, placed in the abdominal cavity, but outside the peritoneum, the kidneys are situated on either side of the vertebral column in the lumbar region. The right kidney is usually placed at a lower level than the left. The appearance of the kidney is so characteristic that the term reniform is usually employed to describe it and bodies of a similar form. It has not inaptly been compared in outline to that of a haricot-bean, the hilus, or depression, through which the ureter, the blood-vessels and nerves enter being directed towards the spine. As a rule, the two kidneys are identical in size ; but occasionally differences in size are encountered as abnormalities quite com- patible with health. In certain rare instances but one kidney exists, this abnormality arising from an intra-uterine coalescence of the two primitive glands. The Size of the Kidney varies with age, sex and general development of the individual. Ordinarily the kidneys measure about 4 inches in length, 2^ inches in breadth, and 1\ inches or more in thickness. The left kidney is sometimes the longer and thinner, the right being shorter and wider. The Weight of the Kidney likewise varies with age and development. In the adult male it usually weighs about 4J- ounces, being somewhat less in the female. According to Glendinning, the two kidneys of the male weigh on an average ounces, and those of the female 9 ounces. According to the observations of Eeid, the average weights of the kidneys are, in 160 observations by him, 4£ to 6 ounces in the adult male, and in the adult female (74 observations) 4 to ounces. The specific gravity of the renal substance is 1052. The superficial colour of the kidney is a deep reddish-brown. Chemically the kidney contains 83 per cent, of water, 1 per cent, of fatty matter, and the 16 remaining constituents almost exclusively represent albuminoid compounds. Like all other glands, the kidney may be structurally regarded as composed of a basement membrane or matrix ; a series of tubes ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 3 for depuratory purposes communicating directly or indirectly with the exterior ; a system of cells for separating and elaborating the ultimate products of waste ; a system of blood- vessels supplying nourishment to the organ and conveying to it the products to be secreted and excreted ; and a system of nerves regulating the circulation of the blood. Independently of these, the kidney possesses a lymphatic system. The functions performed by the kidney in the aggregate are simply those per- formed by the single cell, and may be classified as physical, vital, and chemical; the physical consisting of dialysis and taking place in the glomerulus and Malpighian capsule ; the vital in the special selection manifested by the glandular structure in the discharge of the function of excretion ; and the chemical in the elaboration and the separation of the ultimate products of oxidation in the body. The Basement Membrane or Stroma of the Kidney.— Externally the kidney is invested by a thin and strong fibrous coat, the tunica propria, which is loosely attached to its substance by a delicate areolar tissue and minute bloodvessels. Prolongations from the tunica propria extend inwards in the tissue of the organ, and are continuous with the connective tissue proper presently to be noticed. When the tunica propria is traced to the liilus, it is found to be continuous with the external surface of the infundibulum formed by the dilated portion of the emergent ureter, and the adherent nutrient bloodvessels which enter at this part. On making a section of the kidney from its outer to its inner border the fissure, or hilus, is found to extend some distance into the organ, forming a cavity termed the sinus, into the bottom of which the fibrous coat can be traced. The emergent ureter is greatly enlarged before it leaves the organ by the union of its primary subdivisions forming a chamber termed the pelvis. Into the substance of the organ prolongations of the ureter pass which terminate abruptly in cup-like depressions called the calyces, into which little conical protrusions depend — the Malpighian pyramids. The outer capsule of the kidney consists of connective tissue chiefly of the white fibrous variety, which, on being examined with a high power, is found to contain flattened connective tissue corpuscles. This tissue is most compactly arranged towards the periphery, 4 THE UKINE IN HEALTH AND DISEASE. becoming areolar in its deeper portion, the tenuity of its fibres increasing as it dips down and becomes continuous with the intertubular tissue of the subjacent cortex. Between the cortex and the capsule there is a system of bloodvessels and elongated cells, described by Eberth as a plexus of non-striated muscular fibres. The existence of connective tissue in the kidney, long dis- puted, was first maintained by Goodsir. This view was after- wards combated by Von Wittich, who maintained that the interstices of the secretory and excretory portions of the kidney were merely separated by capillary vessels. This opinion held ground, especially among German histologists, until Arnold Beer published the results of his investigations.* The connective tissue in the normal state is found in greatest abundance at the level of the hilus, and is distributed along the bloodvessels, and serves to support them in the same manner as that of the liver. As the connective tissue is traced inwards from the papillae it becomes less manifest. It contains cell elements, fibres, and, according to Ludwig, lacunar spaces in connection with the lymphatic system. Processes of the connective tissue, as we have seen, dip inwards from the capsule into the cortical substance, and, like the con- nective tissue in other glands, these enlarge on the supervention of interstitial change, and undergo contraction and other morbid changes, thus destroying the glandular tissue and abrogating its proper function, the whole process being the sequence of initial hyperaemia abnormally protracted. This multiplication and change of connective tissue is an important factor in a large class of diseases, not only in the kidney, but in the lungs, liver, and spinal-cord, etc. (cirrhosis). It is in it that abscesses form, and that the great bulk of neoplasms are developed. Axel Key first noticed that connective tissue exists .in the glomerulus, binding together the capillary loops, and becoming continuous with the tissue which surrounds the afferent arterioles, and the medullary substance of which they are branches. From there the tissue may be traced round the arteriolar rectae into the boundary layer between the medulla and the cortex, when it * 'On the Connective Tissue of the Human Kidney in its Physio- logical and Pathological Relations, ' 1859. ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 5 becomes scanty and assumes a hyaline, honeycombed, mem- branous aspect. According to Schweigger-Seidel, in this situa- tion the connective tissue may be branched or spindle-shaped and possess oval nuclei disposed transversely to the long axis of the tubules. On macroscopic (ftaicpug, great) examination a section of the kidney shows certain clearly-defined differentiation of structure. Fundamentally, the gland is seen to be com- posed of an external or cortical portion, and a medullary portion directed from the cortex towards the hilus. The cor- tical portion occupies the entire surface of the organ, is of a dark-brown chestnut colour, and forms a layer of about two lines in thickness. It is friable, easily lacerated, and when this does take place the laceration usually happens in a direc- tion vertical to the surface. The rupture presents an irregular appearance due to an admixture of straight and convoluted tubes and Malpighian bodies. From the cortical substance, and passing towards the hilus, prolongations are sent, which separate and form partitions between the pyramids of Malpighi. These septa terminate near the summit of the papilla, and are known as the columns of Bertini (septula renum). It is in the cortical substance and its prolongations that morbid changes are most frequently found. Between the septula renum another collection of tubes is seen, constituting the pyramids of Malpighi, the bases of which are directed towards the cortex of the organ, and their apices towards the hilus, terminating in the papillae which open into the calyces. The number of these pyramids varies from eight to eighteen. In ultimate structure these pyramids are composed of a series of straight tubes (tubes of Bellini) placed parallel to the axis of the pyramid, and presenting a striated aspect. Passing towards the cortex, these tubes divide and subdivide at very acute angles. At the base of the pyramids of Malpighi they unite with the convoluted tubes ; and it is this union of the collector with a convoluted tube which constitutes a pyramid of Ferrein. The Malpighian Capsule. — By the Malpighian capsule, or capsule of Bowman, is understood the dilated cortical extremity of the uriniferous tubule, whose other extremity terminates in 18 18 Fig. 1. — General View of the Structure of the Kidney (the tubes of Henle not represented). 1, Renal vein ; 2, Renal artery ; 3, Ureter, continuous with the open pelvis ; 4, Cut cortex of the kidney ; 5, Surface of the kidney ; 6, Cor- tical substance ; 7, A Malpighian pyramid with its arteries : 8 8, Papillae of pyramids which have not been divided ; 9, A divided calyx, embracing a pyramid ; 10, Branch of the renal artery between two pyramids ; 11, Malpighian capsule magnified 40 diameters ; 12, Vessels in the centre of the glomerulus ; 13 Efferent vessel of the glomerulus ; 14, Capillary network ; 15, Convoluted tube of the cortical substance x 20 ; 16, Tortuosities of convoluted tube ; 17, Tortuous tubes x 40 ; 18 18 18, Glomeruli x 10 x 20 ; 19, Tortuous tubes x 20 to 25 ; 20, Some tube3 cut. ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 7 the papilla. It embraces within its walls a tuft or network of bloodvessels, termed the glomerulus, from which vessels the urine, with certain of its diffusible salts, is secreted. In structure the capsule consists of a hyaline membr ana propria, thickened, according to Ludwig, externally by a greater or less proportion of a delicate fibrous tissue dipping inwards to form an invest- ment for the glomerulus. The inner surface of the capsule is lined by a layer of epithelial cells. These cells undergo certain physical changes, according to age. In early life they are some- what polyhedral in form, while as age advances they become flattened. They all possess well-marked oval nuclei, which may be distinctly revealed by injecting the renal bloodvessels with a solution of nitrate of silver. In like manner the glome- rulus is covered with its own special epithelial cells, which are considerably larger than those lining the capsule, and remain of Fig. 2. — Diagram showing the Relation of the Malpighian Body to the Uriniferous Ducts and Bloodvessels. (After Bowman.) a, One of the interlobular arteries ; d, Afferent artery passing into the glomerulus ; m, Vascular tuft formed within the glomerulus ; c, Capsule of the Malpighian body (capsule of Bowman) forming the termination of and continuous with t, the uriniferous tube ; e 6, Efferent vessels which subdivide into the plexus p, surrounding the tube, and finally terminate in a branch of the renal vein p. a polygonal shape (cubical). These two epithelial layers con- stitute thus a closed sac, containing an excreting gland. The Glomerulus. — The glomerulus is a tuft of bloodvessels composed of terminal branches of the renal artery and the Fig. 3.— Diagram- matic View of the Loops of Henle, showing their Con- nection with the Malpighian Capsule. {After Gross, of Stras- burg. ) 1, Surface of the papilla ; 2, Surface of the kidney ; 3, Commencement of the medullary portion (between 2 and 3 indicates the extent of cortical sub- stance) ; a a, Glomeruli of Malpighi ; b 6, Tubuli con- torti ; c c, Loops of Henle ; g g y Canaliculi, uniting to form the canal of Bellini — the latter unite with others to form a common canal opening on the summit of the papilla. ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 9 commencing branches of the venous system. On reaching the Malpighian capsule, the afferent artery pierces its homogeneous envelope and breaks up into smaller tortuous branches, which ultimately unite to form an efferent vein, which makes its exit from the capsule near the entrance of the artery, and unites with the intertubular venous plexus surmounting the convoluted tubes, all of which ultimately join the renal vein. At a point opposite to the entrance of the afferent artery and the exit of the efferent vein, the glomerulus becomes continuous with the canal of the convoluted tube. At the point of junction the canal is narrowed, and to this portion the term ' neck of the capsule ' has been applied. Commencing at this neck, the canal, situated in the cortical substance, becomes tortuous, of consider- able size, and is now designated the convoluted tube, in virtue of its appearance. After a short course as a convoluted tube, termed the proximal convoluted iubule, the canal becomes narrowed, and descends in the form of a straight tube towards the papilla. This portion is termed the descending branch, or the small branch of the loop of Henle. Within a variable distance of the papilla the canal abruptly bends upon itself, forming an ascending branch, or great branch of the loop of Henle, which runs parallel with the smaller one, and aga'n narrows into a spiral portion, then dilates into a tortuous tube, forming the distal convoluted tubule, which opens into a collect- ing or straight tubule. It is the junction of the distal convo- luted tubule with the straight tubule which constitutes the pyramid of Ferrein. The distal convoluted tubule is also known as the intercalated portion (S dials tuck, Schweigger- Seidel). As function is specialized in certain portions of the kilney, we accordingly find that the cells lining the secreting tubes differ correspondingly. (1) In che proximal convoluted tubule there is a single layer of epithelial cells, which reduces its lumen to about a third of its whole diameter. In general outline the cells of this section are somewhat cubical ; towards the neck they decrease very markedly in height, and have thus the appearance of ceasing abruptly there. They vary in size throughout the tubule, and their opposed sides are not straight, but slightly 10 THE URINE IN HEALTH AND DISEASE. Fig. 4.— Diagram of the Looped Uriniferous Tubes, and their connec- TION with the Cap- sules of the Glo- me r u l i. ( From Southey, after Lud- wig.) In the lower part of the figure one of the larger branching tubes is shown open- ing on a papilla ; in the middle part three of the looped small tubes are seen de- scending to form their loops (their relative size is not so well indi- cated here as in Gross's figure on page 8. The ascending branch is about thrice the size of the descending). In the upper, or cortical part, two of these tubes, after some enlargement, are represented as becom- ing convoluted, and dilated in the capsules of the glomeruli. curved, the convexity of the one side fitting into the concavity of that in juxtaposition with it. All the cells possess central spherical ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 11 nuclei. Klein describes the structure of these cells as consist- ing of a honeycombed network. (2) In the spiral tubule of Schachowa, the relative size, shape of the walls, and lumen resemble the proximal convoluted tubule. The cells at the commencement of this section are very irregular in shape, some of them being elongated columnar cells with concave sides, while others are broad with convex sides and convex free surfaces, thus resembling mushrooms, and called the fungoid cells of Schachowa. They all possess centrally-situated spherical nuclei. (3) In the descending limb of Henle's loop the epithelial cells become attenuated, and contain oval, flattened, centrally-placed nuclei. (4) In the ascending limb of the loop of Henle the epithelial cells become modified into polyhedral forms with a based rod-like striation. Each cell possesses a strongly-marked spherical nucleus, situated towards the free extremity, which projects into the lumen. (5) In the spiral portion of the ascending limb of Henle's loop the epithelial cells contain oval, irregular, and flattened nuclei placed towards the lumen, which is almost obliterated by the large size of the poly- hedral striated cells. (6) In the cortical portion of the ascend- ing limb of Henle's loop the cells show rod-like structure at their attached bases, and possess flattened or angular peripheral nuclei, occasionally with imbricated processes. (7) In the irregular tubule the epithelial cells are imbricated, and exhibit the rod-like structure more markedly than in any other portion of the renal tube. Each cell contains an oval or angular nucleus towards its periphery. (8) The intercalated section is identical in location and structure with the proximal convoluted tubule. (9) The straight section of the collecting-tube has a small but distinct lumen with a single layer of homogeneous cells, varying in shape from regular polyhedral to flattened or spindle-shaped elements. The cells possess ovoid or spherical nuclei, and may show imbricated processes. (10) The collecting- tube of the boundary layer is lined with epithelial cells of a short columnar variety, resembling those of the foregoing- portions. (11) In the collecting-tubes and ducts of the papillary portion the size of the lumen and its epithelial cells depends on the diameter of the tube, which increases by the successive Fig. 5.— Dia- ghammatic Re- presentation of a Part of the Straight and Convoluted Uriniferous Tubes with the Glomeruli. {From Frey, after a drawing by Midler.) b b, Two large straight tubes in the medullary substance of the pyramid ; c, Con- voluted tubes, several of their terminations in the Malpighian capsules, as in d ; a, Three arteries pass- ing up the pyramid, and dividing into branches to the glo- meruli ; the efferent ves els are also repre- sented, and the net- work of capillaries between them and the ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 13 union of smaller ducts, until it forms ths large duct of Bellini, which debouches on the papilla. Circulation of Blood in the Kidney. — The kidneys are abundantly supplied with blood through the renal arteries, which branch off from the aorta between the two mesenteric arteries. Each is directed outwards so as to form nearly a right angle with the aorta. Owing to the position of the aorta on the spine, the right renal artery, in order to reach the kidney, has a longer course than the left, and it runs behind the vena cava. Both arteries are covered by the renal veins. Kelatively to the size of the kidney the renal artery is large, and the organ is thus highly vascular. On reaching the hilus the renal artery enters the organ between the renal vein and the ureter, and usually divides into four or five primary branches, which may be seen in the sinus to pass in amongst the infundibula. These branches are usually surrounded by a large proportion of adipose tissue. The arteries now further divide and subdivide to enter between the Malpighian pyramids, that is to say, in the substance of the columns of Bertini. They are surrounded by longitudinal and circular bands of muscular fibres, and by a delicate connective tissue, which accompanies them in their course throughout the papillary region. A little before reaching the base of the pyramid they divide and anastomose between one another, the inter- communicating arterial network fo ming an arterial incomplete arch, whose convexity is towards the surface of the kidney. By its concavity this arch gives branches to the pyramids, and by its convexity it furnishes numerous branches proceeding per- pendicularly towards the cortical substance. In the course of these branches short, transverse off-shoots are distributed (in the cortical substance), one to each Malpighian capsule forming its afferent artery, and breaking up in the loop, forms terminal branches anastomosing with the efferent vein. Occasionally the afferent arterioles give off lateral branches before they reach the glomerulus, which ramify around the convoluted tubules. In the portion of the cortical substance which is devoid of Mal- pighian capsules, the interlobular arteries either terminate as afferent arteriolar, or continue towards the capsule, supplying the network of capillaries surrounding the convoluted tubes, or 14 THE URINE IN HEALTH AND DISEASE. anastomose with branches from the lumbar artery, with which the capsule is thus supplied. It is thus obvious that the kidney has a blood- supply independently of the renal artery ; and thus, if the renal artery be tied, the kidney may be injected through the aorta by means of these lumbar branches. From the larger Fig. 6. Semidiagrammatic Re- presentation OF A MALP1GHIAN Body in its Relation to the Uriniferous Tube. {From Kbl- liker. ) or, Capsule of the Malpighian body continuous with b, the mem- brana propria of the coiled ur ini- ferous tube ; c. Epithelium of the Malpighian body ; d, Epithelium of the uriniferous tube ; e, De- tached epithelium ; f t Afferent vessel ; g, Efferent vessel ; h, Con- voluted vessels of the glomerulus. Fig. 7. — Three Malpighian Capsules in Connection with the Bloodvessels and the Urinary Tubes of the Human Kidney. {From Koiliker, after Bowman ) a, Termination of an intertubu- lar artery ; b, Afferent arteries ; e, A denuded vascular glomerulus ; (Z, Efferent vessel ; e, Two of the glomeruli enclosed by the Mal- pighian capsules ; f, Uriniferous tubes connected with them. ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 15 arterial branches existing between the cortex and the medullary structure another system of branches arises. Those entering the boundary layer proceed towards the papilla in groups parallel with and between the renal tubules. These are the arteriohv rectcB, which impart the peculiar banded appearance to the medullary rays. As they approach the papilla they decrease in number owing to the lateral branches which they give off, and around the mouths of the ducts they terminate in a network of capillaries continuous with the vence rectce, which pursue an opposite direction directly parallel. The Renal Vein originates in the efferent vessel of the glomerulus and the capillary venous system of the kidney generally. The efferent vessel, as we have seen, considerably smaller than the afferent, originates in the Malpighian tuft. Penetrating in its outward passage the Malpighian capsule near the entrance of the afferent vessel, it breaks up into a dense network of veins, which surround the convoluted tubes and closely embrace them. The meshes of the labyrinth and peri- phery are smaller and more regular in disposition than those in the medullary structure, which become more elongated. The capillaries of the periphery of the cortex open into minute veinlets, which again empty into larger vessels forming rays, and hence termed vence stellatce. The vence stellatce become inter- lobular veins, and accompanying the interlobular artery between the cortex and the medulla, form a venous arch, hi which the vence rectce, commencing in the papilla, terminate. The blood in the efferent vein of the glomerulus is still red, and hence this vessel is sometimes termed an artery. The specific urinary constituents, such as urea, hippuric acid, etc., are not separated from it until it reaches the convoluted tubes. Unlike all the other venous blood of the body, it is not sur- charged with carbonic acid gas. That of the body in general con- tains 6 per cent, of oxygen, while that of the renal vein contains 16 per cent., or only 1 per cent, less than that of arterial blood. Lymphatics of the Kidney.— According to Sappey, the kidney possesses no superficial lymphatics, while the origin of the deep lymphatics is as yet undetermined. They are in free communication with the lymph spaces which surround the con- 16 THE URINE IN HEALTH AND DISEASE. ■ voluted tubes of the cortex. A plexus of lymphatic vessels exists around the larger bloodvessels which enter the medulla ; and, according to Ludwig and Zawarzkin, a system of intertubular lymph spaces communicates freely with a superficial capsular system. Nerves of the Kidney. — The nerves of the kidney are derived from the renal plexus and the lesser splanchnic. They pass into the renal structure with the bloodvessels ; and, according to Pfliiger, they terminate in the nuclei of the cells. The nervous system, in all parts of the body, controls and regulates the circu- lation of the blood, and thus impressions upon the fibres of the renal plexus which surround the tubuli contorti must influence the secretion of urine, and especially the excretion of urinary ) products. Moreau, in 1868, pointed out that section of the splanchnic nerve was followed, as in cholera, by an intestinal flux ; and Eckhardt, in experiments which he also performed on the splanchnics, found that their section induced hyperemia of the tubuli contorti, albuminuria and increased secretion of urine. Vascular tension, or blood pressure, is one of the physiological factors in the secretion of urine, and thus we have it artificially augmented to an abnormal degree. Hyperemia of the kidney occurs likewise in cases of spinal paralysis, and particularly when the ganglionic nerves are affected. Yulpian found, as the result of observations on a dog subjected to the influence of woorara, that division of the left splanchnic was followed by congestion of the corresponding kidney, the organ assuming a deeper hue, becoming enlarged, and polyuria and albuminuria supervening. The influence of the vaso-constrictor nerves is thereby suspended. The contrary condition, anuria, is brought about by an opposite physiological state, contraction of the arterioles. In Vulpian's experiment there was no extravasation of globules of blood nor desquamation of the tubes. What was especially interesting, the renal vein became larger and redder. On the peripheric end of the cut nerve being subjected to the action of electricity, the kidney and its capsule became pale. They progressively resumed their reddish hue as the current was suspended, while the size of the renal vein diminished. Mental impression may act on the splanchnics in a similar manner, and hence we may witness ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 17 polyuria, and even hematuria. According to Byrani section of the cervical sympathetic diminishes the quantity of urine, while its electric excitation, on the contrary, augments it. Section of the pneumogastric seems to have no influence over the urinary secretion. Bernard states, however, that he has noticed in some experiments an augmentation of urine and a congestion of the kidney from excitation of the pneumogastric below the diaphragm. Arthaud and Butteau, on the contrary, observed an arrest of urinary secretion from excitation of the peripheric end of the pneumogastric. Section of the spinal marrow in the cervical region, by causing a lowering of blood-pressure, arrests urinary secretion. Excitation of the lower portion of the spinal cord produces the same result by contraction of the renal arterioles through the vaso-motor nerves. It is interesting to note, how- ever, that if the splanchnics are previously divided, so as to eliminate vaso-motor action, excitation of the cord determines an augmentation of the secretion and an increase of arterial pressure. Pricking of the fourth ventricle causes polyuria and albuminuria, or glycosuria if the lesion be too high or too low. The physiological factors in the secretion of urine may be regarded as — (1) the function of the glomerulus— osmosis and dialysis ; (2) the circulation of blood hi the kidney — accelerated or slowed ; and (3) vascular tension. Generally speaking, the blood in the capillaries of the glomerulus is subjected to a greater pressure, and that of the interstitial or parenchymatous capillaries of the kidney to a lesser amount of pressure than the blood of ordinary capillaries. The intensity of the pressure is such that, as admitted by all physiologists, a purely mechanical filtration might take place, which would at least account for the first part of the urinary secretion ; but on the nature of the fluid secreted there is a disagreement among authorities. Many theories have from time to time been enunciated as to the urinary secretion. The three which at present find most acceptance are those of Bowman, Ludwig and Kuss. The Theory of Bowman. — According to Bowman, the glomerulus of Malpighi permits only the watery portion of the .urine to filter through, the solid parts of the urine formed in the 2 13 THE UKINE IN HEALTH AND DISEASE. kidney or taken from the blood being secreted by the cubical cells lining the convoluted tubes, and- absorbed by, or incorporated with, the water as it passes along the tubes. Kecognising the difficulty of comprehending how the very diffusible salts of the blood found in the urine did not pass through the tuft -walls and capsule with the water, Bowman himself and Yon Wittich and Donders so modified the theory as to include the nitration of the diffusible salines with the water, while the epithelial cells of the convoluted tubes only secreted the urea and the uric acid. Eecently Heidenhain has reverted to the opinion of Bowman, endeavouring to establish the independent elimination of the watery and the solid portions of the urine. These two processes seem really to take place in two different portions of the kidney. According to Heidenhain, the secretion of water by the kidney may be completely arrested without interfering with the elimina- tion of solid substances injected into the blood, such as indigo- tate and urate of soda. This elimination takes place through the epithelium of the convoluted tubes and the larger branch of the loop of Henle. If the cortical substance of the kidney be cauterized, the secretion of urine is suspended in the portion thus operated upon ; and even in the corresponding region of the medullary substance, whose canals in this case do not contain indigotate of soda. Under these circumstances, however, Heid- enhain has found the cortical canals to be filled with this colour- ing matter ; but the secretion of water having been arrested, the colouring matter was not drawn into the medullary canals. Hence, it is evident that the aqueous part of the urinary secre- tion transudes through the glomerulus, and presumably also from the convoluted tubes. Further, other considerations seem to point to the secretion of the watery portion of the urine by all portions of the kidney, the cortical as well as the medullary substance. In amphibious animals the glomeruli and the renal canaliculi have an absolutely distinct circulation, the glomerulus receiving its blood from the aorta, and the canaliculi from a portal system analogous to that of the liver, composed of venous branches proceeding from the inferior extremity, the oviduct and the dorso-lumbar vein. These are the afferent renal veins. If ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 19 the common aorta be tied, the glomeruli receive no blood, and consequently their function is brought to a standstill. Theory of Ludwig. — According to this theory, blood-pressure performs the principal role in the secretion of the urine. Under the influence of this pressure, the serum of the blood transudes through the walls of the capillaries of the glomerulus minus the albuminates and the fats. The fluid which escapes contains water, salts of the blood, and extractive matters. Having reached the canaliculi, this liquid finds itself in contact with the epithelium of the convoluted tubes, and with the lymph which surrounds the canals, and which is a more concentrated fluid. The lymphatics and the capillaries which surround the canaliculi take up a portion of the water and salts filtered, until the endos- motic equilibrium is established. Ludwig primarily ascribes no role to glandular activity, and the experiments of Goll tend to show that blood-pressure alone is the chief factor in the process of urinary transudation. The quantity of urine augments with pressure, and its concentration is in an inverse ratio to the rapidity of the secretion, and never exceeds a certain figure. All this notwithstanding, the proportion of the urinary principles and of the blood cannot be explained on purely physical laws. And hence, even admitting the theory of Ludwig, the element of glandular activity requires to be invoked. An outstanding diffi- culty of this theory is the question why the albumen of the blood does not pass through the glomerulus with the other constituents. Ludwig' s explanation of this is that the albumen diffuses with great difficulty in presence of the free acid of the urine which is formed in the kidney ; but it is not in the glomerulus that this acid is formed, and it is here that the filtration takes place. Normally the albumen does not transude under two circum- stances : Firstly, when the blood is healthy, the tissues being then consequently healthy ; secondly, when there is neither undue delay nor undue pressure in the capillaries (we know that albuminoids will traverse animal membranes under undue pressure) ; conversely albumen will pass through the glomerular epithelium and the Malpighian capsule under the opposite con- ditions. Otherwise it seems to me that we should simply regard this as one of the ultimate facts of the organism — as constituting 20 THE URINE IN HEALTH AND DISEASE. one of the vital correlations — for which we have no satisfactory explanation to offer. Another difficulty presented by the theory of filtration is the enormous quantity of liquid which must traverse and be taken into the blood in order to furnish the proportion of urea eliminated in twenty-four hours. Besides, if this theory were correct, there ought to be a parallelism between the quantity of urine and the amount of urea excreted ; but in certain cases this does not obtain. In diminishing, for instance, the calibre of the renal artery, the urea relatively diminishes in the urine. In fine, according to the theory of Ludwig, the transudation from the capillary vessels ought to cease when the concentration of the urine should become equal to that of the blood plasma. There would be thus a limit to the concentration of the urine, and it could never become more concentrated than the blood plasma. Hoppe-Seyler found, however, in putting the urine and the serum of the blood of a dog in an endosmometer, that the volume of the urine augmented by withdrawing water from the serum of the blood. It was thus more concentrated than the latter. In this case, however, any influence due to the fibrine is not taken into account. Ribbert, in order to determine whether the urine secreted by the glomerulus becomes concentrated in the convoluted tubes in rabbits, extirpated the medullary substance, and found that the amount of urine was greater. His experi- ments tended in favour of the resorption theory. The Theory of Kuss. — In some respects the theory of Kuss is similar to that of Ludwig, only he evades the difficulty which we have just seen to be presented by the theory of Ludwig, Kuss maintaining that the whole serum filters through the glomerulus, as in the case of ordinary serous transudation. Hence, as the fluid passes along the convoluted tubes, according to him, the albumen is reabsorbed. The urine then would consist of serum less albumen. This looks a particularly clumsy operation on the part of nature, in all things so conservative of material, of force, and of energy. This resorption Kuss holds would be due to the vital activity of the epithelial cells, aided by the feeble pressure of the blood in the pericanalicular capillaries. This theory is held to explain how cysts of the kidney, formed in consequence of obliteration of the convoluted tubes, are not found to ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 21 contain urine, but an albuminous serous fluid, and how in these cases, or when the epithelium of the kidney is diseased, it is unable to resorb the albumen and it thus appears in the urine. It has been found that when albumen has been injected into the blood of rabbits it is eliminated by the glomerulus, and that the same thing happens after temporary ligature of the renal artery. It must be borne in mind that here we are dealing with a patho- logical condition, and that we must not too hastily draw conclu- sions from such data as to normal states and functions. It is thus evident that all the three theories — the three most usually accepted — present difficulties. Pressure of blood is the main factor in determining the amount of the urinary secretion. In order that this secretion take place, the pressure, it is obvious, must be greater than the pressure in the convoluted tubes. It is thus the difference between the two pressures, and the excess of the former over the latter, which determines the secretion. When this difference of pressure is diminished or equalized, either by diminishing the blood-pressure by section of the cord, or by copious bleeding, or by augmenting the pressure in the canaliculi, as when the ureter is ligatured, the secretion of urine diminishes or is totally arrested. The inverse result is produced when the difference is increased, as when the blood-pressure is experimentally aug- mented by ligature of the aorta below the renal artery, the injection of water into the blood, and contraction of the cutaneous vessels, as from cold, etc. The pressure in the renal artery amounts to 120 to 130 millimetres of mercury. All causes which influence the pressure of blood in the renal artery act indirectly on the urinary secretion. Thus, the quantity of urine is augmented simply by increased cardiac activity, and by diminution of the total vascular area, by an augmented amount of blood, as from large draughts of water, injection of water into the veins, etc. The secretion is diminished by opposite causes, such as diminution of the activity of the heart, excitation of the pneumogastric, the action of heat upon the skin, copious sweating, etc. Augmentation of blood-pressure not only raises the amount of urine, but it likewise increases the amount of solid constituents of the urine, though in feebler pro- 22 THE URINE IN HEALTH AND DISEASE. portion. According to Heidenhain, and in this he is supported by Paneth and Munck, the augmented pressure acts by acceler- ating the passage of blood through the glomerulus. Epitome of the Relation between Urinary Secretion and Arterial Pressure.* A. Secretion of urine may be increased : (a) By increase of the general blood-pressure — by (1) Increase of the force or frequency of heart- beat (digitalis, alcohol, etc.), (2) Constriction of the small arteries in other areas than that of the kidney (skin from cold, etc.). (b) By increasing the local blood-pressure, by relaxa- tion of the renal artery ivithout compensating relaxation elseivhere : (1) Division of the renal nerves (causing poly- uria). (2) Division of the renal nerves and stimulation of the cord below the medulla (causing greater polyuria). (3) Division of the splanchnic nerves. As these nerves are distributed to other regions, other vessels are dilated besides the renal artery, and the polyuria is consequently less than in 1 and 2. (4) Puncture of the floor of the fourth ventricle, or mechanical irritation of the superior cervical ganglion of the sympathetic. The renal arteries are thus dilated. B. Secretion of urine may be diminished : (a) By diminishing the blood-pressure — by (1) Diminution of the force or frequency of the heart-beats. (2) Dilatation of vessels in other areas than the kidney (skin in hot weather). * Kirkes' 'Physiology.' ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 23 (3) Division of the cord below the medulla, causing vascular dilatation of the abdo- minal area and suppression of urine. (b) By increasing the blood-pressure by stimulation of the spinal cord below the medulla, when the constriction of the renal artery is not com- pensated for by general increase of the blood- pressure. (c) By constriction of the renal artery, by stimulating the renal or splanchnic nerves or the spinal cord. The condition of the blood exercises a not less marked influ- ence on the secretion of urine. In the normal condition the composition of blood oscillates within a certain range. Whenever this range is exceeded, that is to say, whenever any constituent is found in excess in the blood, even if it be a normal constituent, such principle is eliminated by the kidney, though not normally so eliminated. Thus, if an excess of albumen be taken into the blood, as may happen from an excessive indulgence, for instance, in raw eggs, albumen is found in the urine. What I have been in the habit of terming the vital correlation is disturbed, and qua this a pathological state is induced. If the theory of Kuss be the correct one, it is difficult to see why the albumen in this case is not absorbed by the epithelium of the convoluted tubes. It is in this manner that draughts of water augment the watery portion of the urine, the specific gravity of the blood being restored to its normal equipoise. Similarly, chloride of sodium, phosphate of soda, and most other salines, thus appear in the urine in proportion to the dose administered. Glycosuria shows itself when the glycose exceeds 0*6 per 100 in the blood. Finally, all diffusible substances introduced into the organism rapidly pass into the urine. As the nature of the urine thus depends on alimentation, why the secretion of herbivora and carnivora is different, and how, is apparent. The urine is thus a depuratory and antitoxic secretion. Hence, when nephrectomy or ligature of the ureter is practised, toxic manifestations appear more rapidly ; and, conversely, when the urinary secretion is active, poisonous manifestations are retarded and mitigated. When the 24 THE UEINE IN HEALTH AND DISEASE. urinary passages eliminate the poison to the extent that it is ingested, toxic phenomena do not appear at all. This happens, according to Bernard and Hermann, when curara is introduced into the stomach. The role of cellular activity on the secretion of urine is undoubted, as shown by experiments, and especially by artificial stimulation of the kidney. If the urinary secretion be arrested by diminishing the blood-pressure by section of the cord, or by retarding the venous circulation of the kidney, secretion may be re-established by the employment of certain diuretics, such as acetate of soda, urea, etc. Abeles found that when he added to the blood of the kidney blood unmixed with urea, not a drop of blood flowed from the ureter ; but when he added blood to which urea had been added, the blood flowed more quickly, and urine was secreted. Abeles therefore infers that urea paralyzes the vaso-constrictor nerves, and excites the vaso-dilators of the kidney ; but the subsequent experiments of Munck and Phillips seem to demonstrate that the effect is specially on the secretory cells. The influence of the epithelial cells is further demonstrated by the mode of action of the different salts of the urine. Senator and Munck have shown that if the venous circulation of the kidney be arrested at the same time that the quantity of urine diminishes, the proportion per cent, of urea diminishes, while the proportion per cent, of chloride of sodium does not vary. Lepine and Aubert found that by temporarily occluding the ureter of one side, and com- paring the secretion of the two kidneys, that of the side operated on was more concentrated and the phosphates were less perfectly eliminated, but the chloride of sodium was eliminated as well as on the sound side. Urine normally appears as a pale, straw-coloured and trans- parent fluid. It is an excrementitial liquid, representing the unutilized material introduced into the organism for the purpose of nutrition, as well as the products of organic disassimilation. The terms ' transparency ' and ' aspect ' of urine are often con- founded. ' Aspect ' obviously refers to the naked-eye appear- ance, and ' transparency ' to transmissibility of light. Transparency. — When passed, normal urine is usually clear and transparent. After a period of repose flakes of mucus ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 25 often appear, which, according to the density of the urine, either remain suspended in the fluid or are deposited. This mucus in the normal condition scarcely affects the transparency of the urine, but in certain affections of the urinary organs its amount may be so great as to render the urine opaque. This mucus is composed of epithelial debris from the bladder, the ureters, and the pelvis of the kidney. Frequently the urine becomes turbid when exposed to a low temperature, owing to the precipitation of bodies normally held in solution at a higher temperature. Again, loss of transparency may be due to the presence of adventitious chemical compounds only found in a pathological state, such as earthy phosphates of calcium and magnesium (in abnormal amount), and such constituents as pus and chyle. Odour. — In the normal condition fresh urine has a peculiar aromatic odour. The smell of urine is said to be due to the presence of phenylic, taurylic and damoluric acids. The urine in diabetes has a sweetish, hay-like smell. Urine containing cystin has a smell similar to that of sweetbriar, which afterwards becomes very disagreeable. Certain medicaments impart their odour to the urine, such as turpentine (which imparts to it the smell of sweet-violets), copaiba, cubebs, oil of santal-wood, asparagus and garlic. When the urine contains decomposing blood or pus it has a putrid odour ; and when it has undergone decomposition in the bladder it exhales an ammoniacal odour, and sometimes gives off sulphuretted hydrogen. Colour. — The colour of urine varies according to concentra- tion or dilution, to the presence of pathological pigments and to variations in dieting. It usually ranges from a pale straw-colour to a reddish yellow. The morning urine, which is called the urina sanguinis, is of a deeper colour than that emitted during the day or after the injection of large draughts of water — the urina potus. Occupying an intermediate place between these two in respect of colour, we have the urine evacuated some time after a repast — the urina chyli. The urine of the infant is generally paler than that of the adult, and during the first hours of existence it is entirely colourless. In acute febrile maladies, the colour of the urine is intensely deep, 26 THE URINE IN HEALTH AND DISEASE. varying from a deep yellow to the reddish-brown colour observed in certain chronic affections. In diabetes, hysteria, anaemia, and granular kidney, it is usually pale. Here there is polyuria ; and in the case of the granular kidney the urine is of low specific gravity, as the convoluted tubes are to so great an extent denuded of their epithelium, and the chief constituents of the urine are consequently not eliminated (Black's ' Lectures on Bright' s Disease,' p. 82). In nervous affections the urine is frequently colourless (urina spastica). In affections of the liver and biliary passages, the presence of bile pigments in the urine occasions a yellowish-green or brownish-green colour (icteric urine). It may also be observed that in being thus eliminated the bile pigments set up so much irritation as to cause the appearance of yellowish tube-casts in the urine. The pre- sence of blood gives to the urine a more or less intense red colour, as we find it in the early stages of acute nephritis, calculous nephritis, cancer of the bladder, etc. In the condition termed hemoglobinuria, haemoglobin exists in the urine, which is thus coloured red. In certain cases of melanotic cancer the urine is coloured black. Certain medicaments alter its colour. Thus, santonin, rhubarb (crysophanic acid) and senna impart to it a yellowish colour. Saffron causes it to become of a greenish colour. The coloration caused by the pigments of senna and of rhubarb is not unlike that occasioned by the presence of blood, but it is easy to establish the distinction. The urine coloured by the former becomes more limpid and clearer in contact with a mineral acid, while that by the latter does not become clearer, but rather becomes of a deeper colour. Further, urine containing pigments of rhubarb and of senna give with ammonia or with potash a purple colour. The yellowish coloration due to san- tonin oscillates from yellowish-red to a reddish-purple in pre- sence of an alkali. ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 27 Krukenberg gives the following table as to urine colours : Pathological and other Urine Colours. Colour of Urine. Cause of Colora- tion. Pathological Con- dition. Pa'e yellow to colour- less. Diminution of normal pigments. Anaemia, chlorosis, dia- betes, and other ner- vous attacks. Dark yellow to brown red, easily deposit- ing a sediment. Increase of normal or occurrence of patho- logical pigments. Acute febrile diseases. Yellowish and milky. Fatty drops floating in urine. Chyluria. Suspended pus cor- puscle?. Pyelitis, or other puru- lent disease. Green, or yellow green. Bile-colouring matter. Jaundice. Greenish-yellow; later greenish -brown, or approaching black. Decomposed haemo- globin and various chromogens. Car bolic acid urine is similar. Haemorrhage into the kidneys in long-con- tinued intermittent fever ; also melano- tic cancer. Red or reddish. Unchanged haemoglo- bin. Haemorrhage, or hae- moglobinuria. Pigments which are taken up with the food, such as madder, bilberries, logwood, fuchsin, etc. Brown. Bile- colouring matters and methaemoglobin. Brown-yellow to red- Substances which are introduced into the brown, becoming organism with senna, rhubarb, chelidonium, blood-red on adding etc. alkalies. Fluorescence, Temperature, etc. — Normal urine is slightly fluorescent. With pale urine the fluorescence is bluish ; with reddish-yellow it is green or yellow. Albuminous urine is more fluorescent than normal urine, and urine which has become * Grundriss d. Med. Chem. Analyse, 1884, S. 78. 28 THE URINE IN HEALTH AND DISEASE. alkaline more than undecomposed urine. All normal urines cause a right deviation of the plane of polarization. When the urine is albuminous the deviation is to the left. Saccharine urines cause a right : handed deviation proportionate to the quantity of sugar. When the urine is agitated, a froth appears which rapidly dis- appears on repose. With albuminous and saccharine urines the froth is more abundant and disappears more slowly. The normal temperature of urine is about 37° C. ; but in certain acute affections, such as pneumonia, scarlatina, rheumatism, etc., the temperature rises correspondingly with that of the body. In cases of idiopathic tetanus, it may rise as high as 44° C, and fall as low as 26° C. in cases of tubercular meningitis. According to Feltz, Eitter, Bouchard, etc., normal urine is toxic. If from 90 to 100 grammes be injected into the veins of a rabbit weighing 2 kilogrammes, the animal is poisoned by lower- ing of its temperature. The toxicity of the urine depends on various circumstances ; for example, cerebral activity, muscular activity, sleep, alimentation, etc. Pathological urines are not necessarily more toxic than the normal. They may even be less toxic. In nephritis the urine is not more toxic than distilled water, a circumstance doubtless due to the very small amount of urinary constituents contained in the urine, especially in that of the granular kidney. Quantity of Urine. — The amount of urine secreted in twenty-four hours averages in a healthy male individual from 1,400 to 1,500 c.c.,° or from 49 to 50 ounces. In the female the volume is less. It oscillates between 1,000 and 1,200 c.c. For obvious reasons, the amount is diminished when the skin is active, and vice-versa. Contraction of the cutaneous vessels, as from cold, etc., stimulates and augments the secretion of urine. The smallest amount is secreted between 2 a.m. and 4 a.m., and the greatest between 2 p.m. and 4 p.m. If the average quantity of urine secreted be compared with the weight of the body, we find that for each kilogramme there is eliminated, on an average, 1 c.c. of urine per hour. In the aged the volume is less. The quantity secreted by the infant at the * 100 c.c. — 3 \ ounces. ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 29 breast, compared with its body-weight, is three or four times greater than in the case of the adult. As a rule, the largest amount of urine is eliminated about two hours after a repast, the least during the night, and the medium amount in the morning. The secretion is augmented by abundant draughts, such as of ordinary water, beer, coffee, and water holding salines in solution. If after large draughts of water violent exercise be indulged in, the augmentation of the volume of the urine is less, as much of the fluid is eliminated by cutaneous transpiration. During winter, when the pulmonary and cutaneous exhalations are much less abundant than in summer, a greater quantity of urine is secreted and vice-versa. Excitable individuals secrete more urine, and in most people nervous excitement is attended with increased micturition. The urinary secretion is less when the amount of fluids ingested is diminished. After parturition, when the secretion of milk com- mences, the quantity of urine secreted diminishes. Hydruria and Polyuria. — Under certain circumstances patients pass from 10 to 12 litres of urine in twenty-four hours. There then exists polyuria, and of this state two varieties are recognised : First, Polyuria properly so called, which is divided into saccha- rine or diabetic polyuria, and the polyuria of diabetes insipidus, when there is no sugar in the urine. Second, Simple Hydruria. In the first case, the percentage of solid matters to the litre of urine is either normal, or sometimes augmented. In the second case the fluid matters are almost normal in relation to the amount passed in twenty-four hours, while feeble in proportion to the litre. In this case there is no hypersecretion of solid matters, but there is a dilution of them by the abnormal amount of water. Certain medicinal agents exercise a marked influence over the urinary secretion. The diuretics markedly augment the secre- tion, and of these the most important are alcohol, nitrous ether, nitrate and acetate of potash, squills, digitalis, broom, caffeine, etc. Certain other medicines diminish the urinary secretion, such as opium (and especially its alkaloid, codeia), belladonna, salts of iron and copper (especially the citrate of iron with 30 THE URINE IN HEALTH AND DISEASE. quinine), ammonia-citrate of iron, etc. Cantharides and arsenic may entirely suppress the urinary secretion. Pathological States influence the quantity of urine. In acute febrile affections, as in pneumonia, pleurisy, typhoid fever, and acute muscular rheumatism, the quantity is markedly diminished ; it then augments as the intensity of the disease diminishes, and during convalescence it becomes normal, and sometimes greater in quantity than in health. In cases of anaemia, profuse loss of blood, and in cholera the quantity is very much diminished. In cholera the diminution frequently amounts almost to anuria 9 and this condition may continue for days, to be followed by polyuria. The urine is likewise diminished in dropsies, gout, and atrophic cirrhosis of the liver. In the various forms of diabetes, as from glycosuria, phosphaturia, etc., the quantity of urine is always augmented. Variations of Density and of Solid Residue in Disease. — In most acute and chronic diseases, both the density of the urine and the amount of solid residue undergo great variations, which, from the point of view of diagnosis, are of primary importance. In the majority of acute affections the urine passed is markedly concentrated, sometimes attaining to a density of 1035. This is chiefly due to the augmented excretion of urea, sulphates, and alkaline phosphates. We find the same condition in chronic affections, where there is disturbance of normal metamorphosis,, as in diabetes, gout, etc. In diabetes the urine may attain a density of 1050. In certain forms of Bright's disease* (the cirrhotic kidney),, and in the amyloid forms of kidney disease, the specific gravity of the urine is very low. It sometimes descends to a specific gravity of 1005, or 1004. The excretion of urea is here diminished, owing to desquamation of the cells of the convoluted tubes. The specific gravity is also diminished in cases of poly- uria and simple hydruria, and likewise in most nervous affections attended with excitement. The Specific Gravity of the urine in the normal state ranges from 1015 to 1025. After excessive draughts of water it has * Vide 'Lectures on Bright's Disease,' by Aut! or. J. and A.. Churchill, London. ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 31 been known to sink as low as 1002 ; and according to Dr. W. G. Smith, it has risen after great sweating and forced marches from 1035 to 1040. The specific gravity in infants is as low as from 1003 to 1006. The average normal density may be taken as 1020. The average density in the female is somewhat less. It may be regarded as 1016. The density varies with the time of the day, and the nature of the alimentary substances ingested, muscular activity, etc. A healthy adult male excretes about 70 grammes, or 2^ ounces, of solids in his urine per diem. Determination of the Density of Urine. — In practice the determination of the density of urine is determined by means of the urinometer. This instrument is so graduated as to indicate to half a degree a density varying from 1000, that of water, to 1040, beyond which the density of urine rarely passes. Urinometer s are generally graduated for a temperature of 15° C. Where absolute accuracy is necessary, the urine must be of this temperature. If the urine be in quantity in- sufficient for the employment of the urinometer, the specific gravity may be obtained by weighing by means of a small flask, the picnometer. Let P be the weight of a given volume of urine, and_£? the weight of an equal volume of distilled water at the same temperature ; then P divided by p will give the density of the urine. P Weight of urine. ~~ p Weight of water. By means of the hydrostatic balance of Mohr the specific gravity may be obtained with greater precision and rapidity. Estimation of the Total Solids of the Urine. — An approxi- mate to the total solids of the urine may be obtained by means of what is known in this country as Christison's formula, and abroad as that of Haeser or Trapp. If the last two figures of the specific gravity as expressed in four figures be multiplied by 2*33 (Christison and Haeser), or by 2 (Trapp), the result will give in grammes the total solids in 1,000 c.c. The weight of the solid residue of the urine, or the amount of solids which the mine holds in solution, averages 47 grammes per litre in a healthy man, and 37 in the female. This residue is composed of organic 32 THE URINE IN HEALTH AND DISEASE and mineral substances. The former always exist, in the normal condition, in greatest abundance. In order accurately to deter- mine the amount of these solids, 10 c.c. to 15 c.c. of urine are ni3asured by means of a pipette, and are allowed to flow into a glass vessel, which is to be hermetically sealed, and whose weight has been previously determined. The capsule is then heated to desiccation. The capsule and contents are now weighed, after having been allowed to cool, in juxtaposition to sulphuric acid, under a glass shade. From the weight thus obtained that of the capsule is deducted, and the weight of the dry residue is then determined. This procedure, however, does not give absolutely accurate results, for in the process of evaporation at 100° C, and desicca- tion at 105° C, a certain amount of ammonia resulting from the decomposition of urea is given off. In order to obviate this, from 1 to 2 grammes of urine are to be weighed between two watch- glasses. The upper one is then removed, and the lower one, con- taining the urine, is placed in a vacuum in presence of sulphuric acid. After the space of twenty-four hours, a new weighing is made to determine the exact amount of the solid residue. If it is desired to determine separately the proportion of mineral sub- stances as apart from the proportion of organic substances con- tained in the residue of the urine, it suffices to destroy the latter by incineration. In this case a platinum crucible must be em- ployed, and careful weighing be resorted to. Reaction of Normal Urine. — Normal urine always possesses an acid reaction. It reddens blue litmus. This reaction is only rarely due to the presence of a free acid. It ought rather in most instances to be attributed to acid phosphate of soda. It may, however, be occasionally due to combinations of uric, hippuric, and lactic acids. In the normal condition the degree of acidity is not uniform. The urine secreted during the night is more acid ; that passed after a meal is less acid. Milk diet and alcoholic beverages augment the acidity, and vegetable diet and abstinence diminish it. Determination of the Degree of Acidity. — The degree of acidity of urine is determined by comparing the saturating power of urine with that of an acid, such as oxalic acid. With ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 33 this view we find out how much of the latter corresponds to the non- saturated acid contained in a measured quantity of urine by neutralizing it with an alkaline solution, of which each cubic centimetre represents a determined quantity of oxalic acid. An alkaline solution of caustic soda is employed so diluted that each c.c. corresponds to 10 milligrammes of oxalic acid. The acid solution is prepared by dissolving 1 gramme of non-effloresced pure oxalic acid in 100 c.c. of distilled water. Hence is obtained a liquor containing in each c.c. 10 milligrammes of oxalic acid. Of a given specimen of urine to be tested, 100 c.c. are placed in a glass vessel, and by means of a burette the soda solution is added drop by drop. After the addition of every demi- cubic centi- metre, the liquid is stirred with a glass rod, and one drop of the solution is then removed and placed on a piece of blue litmus paper. If the reaction is still acid, as manifested by a reddening of the paper, the soda solution is added until this reaction is no longer produced. The number of c.c. of the soda solution necessary to neutralize the urine is then noted. It is thus eas}- to calculate how much oxalic acid corresponds to the acidity of 100 c.c. of the urine, for we know that 1 c.c. of the soda solution corresponds to 10 milligrammes of oxalic acid. If, for example, 12 c.c. of the soda solution were required to neutralize 100 c.c. of the urine ; then *010 x 12 = 0'12 grammes of oxalic acid. Other- wise, the estimation of the acidity of the urine may be obtained by means of this standard solution, and a solution of phenol- phthalein, by which the point of neutralization is indicated. Phenol-phthalein, one of the coal-tar products, is devoid of colour in the acid and neutral states, but becomes of a deep magenta colour in presence of an alkali. The standard solution of soda is the normal volumetric solution of the British Pharma- copoeia, of which 100 c.c. are made up to a litre. The litre contains 40 grammes of pure caustic soda, and each c.c. of this solution represents an equivalent of *0063 grammes of crystallized oxalic acid. Mode of Estimation.— Place 10 c.c. of the urine to be examined into a porcelain dish, and add two or three drops of phenol-phthalein solution. This solution is made by dissolving 0*2 to 0*3 grammes in 100 c.c. of alcohol. From a 10 c.c. 3 34 THE URINE IN HEALTH AND DISEASE. measure graduated to tenths of a c.c, drop into the urine the soda solution, constantly stirring, until the permanent pink tinge has been produced, which indicates that the acidity has been overcome. Eead off the amount of the standard solution, each c.c. of which corresponds to *0063 grammes of crystallized oxalic acid; then the number of c.c. of the soda solution multi- plied by -0063 will represent the acidity expressed as grammes of crystallized oxalic acid per 10, and this result multiplied by 100 will represent the acidity per 1,000 of urine. ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 35 Table showing' the Amount of Acidity, expressed as Oxalic Acid in parts (by weight) per 1,000 (by volume) for the number of c.c. of decinormal Alkali required to neutralize 10 c.c. of Urine. C. C. to Neutralize Oxalic Acid grammes per 1,000 c.c. C. C. to Neutralize Oxalic Acid grammes per 1 ,000 c.c. C. C. to Neutraliza Oxalic Acid grammes per 1 ,000 c.c. o-i 0-063 4-6 2-898 9-1 5-733 0-2 0'12i 47 2-961 9 2 5-796 0-3 0-189 4-8 3-024 9-3 5-859 0'4 0-252 4-9 3-087 9-4 5-922 0-5 0-315 5-0 3-150 9-5 5-985 0-6 0-378 5-1 3-213 96 6-048 07 0-441 5 2 3-276 9-7 6-111 0-8 0-504 5-3 3-339 9-8 6-174 0-9 0-567 5-4 3-402 9-9 6-237 1-0 0*630 5-5 3-465 io-o 6-300 1-1 0693 5-6 3-528 10-1 6-363 1-2 0-756 57 3-591 102 6 426 1-3 0*819 5 8 3-654 10-3 6-489 1-4 0-882 5-9 3-717 10-4 6-552 1-5 0*946 6-0 3-780 .10-5 6-615 1-6 1-008 6-1 3-843 10-6 6-678 17 1-071 6-2 3-906 10-7 6-741 1-8 1-134 6-3 3-969 10-8 6-804 1-9 1-197 64 4-032 10-9 6-867 20 1-260 6-5 4-095 11-0 6-930 2-1 1 323 6-6 4-158 11-1 6-993 2-2 1-386 6-7 4-221 11-2 7*056 2-3 1-449 6-8 4-284 11-3 7*119 2-4 1-512 6 9 4-347 11-4 7*182 2-5 1-575 7-0 4-410 11-5 7*245 2-6 1-638 7-1 4-473 11-6 7-308 27 1-701 7-2 4-536 11-7 7-37L 2-8 1-764 7-3 4-599 11-8 7-434 2-9 1-827 7-4 4-662 11-9 7-497 3-0 1-890 7-5 4-725 12-0 7*560 3-1 1-953 7-6 4-788 12-1 7-623 3-2 2 016 7-7 4-851 12 2 - 7-686 3-3 2-079 7-8 4-914 12-3 7-749 34 2-142 7-9 4-977 12-4 7-812 3 5 2-205 8-0 5-040 12-5 7 875 3-6 2-268 8-1 5-103 12-6 7-938 37 2-331 8 2 5-166 12-7 8*001 3-8 2-394 8-3 5-229 12-8 8-064 : 3-9 2 457 8-4 5-292 12-9 8-127 4-0 2-520 8-5 5-355 13-0 8-190 4-1 2-583 8-6 5-418 13-1 8"253 ' 4-2 2 646 8-7 5-481 13-2 8-S16 t 4-3 2-709 8 8 5-544 13-3 8-379 4-4 2-772 8-9 5-607 13-4 8-442 4-5 2-S35 9-0 5*670 13-5 8-505 36 THE URINE IN HEALTH AND DISEASE. Or let a solution of oxalic acid be made containing 6*3 grammes per litre in distilled water. Put into a glass vessel 10 c.c. of this standard acid solution, adding three drops of an alcoholic solution, of phenol-phthalein, and determine the volume N of a dilute alkaline solution of potash or soda requisite to saturate the acid solution. The 10 c.c. of the oxalic acid solution contain 63 milli- grammes of oxalic acid, or an equivalent of 49 H 2 S0 4 . The alkaline solution is added by means of a graduated burette. Kead off the number N of c.c. used to neutralize the acid. This being ione, repeat the operation, putting into the glass vessel 10 c.c. of the urine, instead of the acid solution, and having added the alkaline solution until the earthy phosphates show a milkiness, add three drops of phenol-phthalein solution, and then con- tinue the addition of the alkaline solution until a persistent rose-tint appears. Then read off the number of c.c. of the alkaline solution required to effect this change ; hence N : 49 : : N" : x. Estimation of the Alkalinity of the Urine. — The estimate of the alkalinity of the urine is determined by its power of neutralizing a solution of oxalic acid, every 10 c.c. of which are equivalent to 17 milligrammes of ammonia. Place 10 c.c. of the acid solution in a glass jar, and from a burette add the urine. Variations in the Reaction of the Urine. — Certain medicinal agencies modify the reaction of the urine ; alkalies, alkaline carbonates, and vegetable acids (converted in the system into carbonates), render it alkaline. In typhoid fever the acidity is much above the normal. It augments with the intensity of the fever, and diminishes as the fever disappears, the urine be- coming alkaline during convalescence. The same thing obtains in cases of pneumonia, pleurisy, rheumatism, etc. In diabetes and rickets there is preternatural acidity. Mineral acids, being often eliminated without undergoing change, render the urine acid. In cases of general debility, chloro-angemia, and depressing affections of the nervous system, the urine is slightly alkaline. When the vegetable acids are taken in large quantity, the ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 37 earthy phosphates may be precipitated. In this case an alkaline reaction is imparted to reddened litmus. This blue colour per- sists after desiccation. It is otherwise, however, if the alkalinity be due to the decomposition of urea, and its transformation into carbonate of ammonia. In this case the litmus which has become blue becomes red if heated, owing to the volatilization of carbonate of ammonia, and a glass tube moistened with hydro- chloric acid evolves white vapour if held above the urine (chloride of ammonium). The alkaline fermentation of urea may take place in the bladder, and then the urine is alkaline when voided. It exhales a foetid odour, and usually contains a deposit of pus, with crystals of triple phosphates, urate of ammonia, and amorphous granulations of carbonates and phosphates of lime and magnesium. In cases of cystitis and paralysis of the bladder this is a frequent occurrence. Urine may be voided acid, and become alkaline on exposure to air. Chemical Composition of the Urine. — Normal urine con- tains substances which, having served their purposes in the organism, fall to be eliminated as refuse products. Of these substances the normal elements of the urine comprise two groups, the one formed of organic elements, which are the products of retrogressive metamorphosis, the other of inorganic elements. They may be thus enumerated : Organic Elements. — Urea, creatinine, creatine, xanthine, uric acid, allantoine, oxaluric acid, hippuric acid, benzoic acid, succinic acid, oxalic acid, phenols, sulphocyanic acid, colouring matters, mucine, and leucomaines. Inorganic Elements. — Soda, potash, lime, magnesia, iron, combinations of hydrochloric, sulphuric and phosphoric acids, phospho-glyceric acid, silicic acid, ammonia, nitric and nitrous acids, peroxide of hydrogen, carbonic acid gas, oxygen and nitrogen. The elements of the first group thus exist in greater abundance than the second. One kilogramme of urine contains these substances in the following proportions : 33 THE URINE IN HEALTH AND DISEASE. organic elements == 32*114 grammes, consisting of Urea 24*270 grammes. Uric acid 0*400 Hippuric acid ... ,.. ... 1*000 Creatinine and creatine ... ... 1*000 ,, Xanthine 0*004 ,, Colouring matter ... ... ... 5*440 ,, inorganic elements = 15*530 grammes. Chloride of sodium ... ... ... 10*231 grammes. Alkaline sulphates ... ... ... 3*100 ,, Alkaline phosphates .. . ... ... 1*431 ,, Alkaline phosphates of magnesia ... 0*455 Alkaline phosphates of lime ... 0*313 ,, Toxicity of the Urine. — By injecting urine into the veins, he observed the following results : myosis, acceleration of the respiration, difficulty of movement (akinesis), somnolency, polyuria, disappearance of the corneal reflexes, and convulsions. It is not probable that these results bear any relation to the amount of urine injected, for in the case of pure water 122 c.c. per kilogramme are required to kill a rabbit ; while the injection of 46 c.c. of normal urine causes death. The toxicity, therefore, is in the urinary constituents. Taking urea in an isolated form, Bouchard found that the intravenous injection of 6*43 gr. killed a rabbit. The mineral salts, and especially those of ammonia and potash, are very toxic. They cause convulsions. The toxicity of the urine is diminished by decolorization with carbon. It probably removes other constituents than pigments. That the toxicity of urine is not due to volatile principles is shown by its persistence after boiling. Bouchard has demonstrated that the matters soluble in water are less toxic than those which are soluble in alcohol. The latter cause coma, diuresis, and abundant ptyalism. The elements soluble in water cause convulsions and myosis. Urine secreted in the waking state is more toxic than that secreted during sleep ; the latter is convulsive, the former narcotic. According to Bouchard, urcemia is a poisoning re- ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 39 suiting from all the urinary constituents, although in unequal proportions, accumulating in the blood through interrupted elimination by the kidney. Pathological Sediments and Concretions.— The proportion of the normal constituents of the urine undergoes wide variation apart from that due to alimentation, age, sex, etc., in certain pathological conditions. Here there are found in the urine elements which it does not contain in the normal state, and which constitute an important diagnostic sign. Of these the most important are albumen, and other albuminoid bodies, such as globulin, hemialbumose, haemoglobin, and peptones, sugars (especially glucose), elements of the bile (biliary acids, cholesterine, etc.), acetone, tyrosine, and leucine, cystine, fats, etc. All the normal and all the pathological elements are usually found in solution in the urine, but sometimes they are precipitated more or less quickly after micturition, or even in the urinary passages. The urine is said then to contain sediments whose examination should be carefully made. Sometimes these sediments are composed of insoluble pathological elements, which are never found dissolved in the urine. When these sediments form in the urinary passages, they may, instead of being eliminated, increase by accretion in the bladder or kidney and constitute calculi. Accidental Elements of the Urine. — The greater portion of medicinal agents, either given as such or as poisons with criminal intent, are eliminated by the urine, and can be discovered there. These constitute the accidental elements which are of importance both to the physician and to the toxicologist. 40 THE UEINE IN HEALTH AND DISEASE. Eeactions of Normal Urine, and Significance. r The urin e is acid (acidity | due usually to acid phos- It reddens I phate of sodium, rarely to blue -I free acid). Occasionally litmus, j the acidity may be due to I acid combinations of uric, ^hippuric, and lactic acids. f It evolves a gas which lenders red litmus blue. The deposit contains triple phosphates (ammonio - phos- phate of mag- nesia). It ren- ders red litmus paper blue. The urine is alkaline. -On being • heated in a test- tube It ' does not' The £ r ine evolve gas. The alkaline deposit contains V triple phos-J T0 ^- • from the bladder. phate. The urine has become ammoniacal from decomposition of the urea (3CH 4 N 2 0 = H3C3N3O3+ 3NH 3 ) urea cyanuric ammonia acid 'Sufficiently con-^ centra ted , on be- Alkalinity ing treated with due to an acid it evolves V alkaline a gas which ren- carbon - ders lime-water ates. turbid. J ~\ Alkalinity Treated simi- due to larly, it does not \ alkaline evolve a gas. I phos- J phates. 1. A little hydrochloric acid added to a large quantity of urine (5 c.c. to 100) causes coloured crystals of uric acid of various shapes to separate out after ten or twelve hours. A large quantity of hydrochloric acid added to a little urine (3 to 1) causes the formation of indigo blue and indigo red, the urine becoming pale red, then brownish- red, or violet to deep blue. This coloration may be due to the oxidation of other chromogens, such as compounds of skatol and the reducing substances. 2. If some urine be gently poured on the surface of common red nitric acid, a garnet-red zone forms at the surface of contact (Hiller's 'urophaein' ring), which is better seen against a white background. (In urines rich in uric acid, just over the ring there may be a white layer caused by the separation of urates, which may be mistaken for albumen.) 3. Caustic soda as well as ammonia precipitates out the phos- phates of the alkaline earths, which separate partly in bunches of long needle-shaped crystals, partly in the amorphous form. 4. Warming with phospho-molybdic acid causes, after acidu- lation with nitric acid, a lively blue coloration, due to its action on the urates. ANATOMY AND PHYSIOLOGY OF THE KIDNEY. 41 5. Iodized starch is decomposed by urine (presence of H 2 0 2 ). 6. By adding mercuric nitrate in solution for some time a clouding arises, which disappears on agitation, due to the forma- tion of sodium nitrate and perchloride of mercury ([N0 3 ] 2 Hg-f 2NaCl=2NaN0 3 +HgCl 2 ) soluble in acid urine. After all the chloride of sodium is decomposed a permanent precipitate forms, due to a combination of the urea with a salt of mercury. (Basis of Liebig's method of estimating urea.) 7. Chloride of barium precipitates baric sulphate, BaS0 4 , and phosphate, Ba 3 (P0 4 ) 2 ; when this precipitate is dissolved in hydrochloric acid a cloudiness is left. 8. Nitrate of silver precipitates silver chloride, AgCl, and phosphate, Ag 3 P0 4 ; the latter first, afterwards all the chlorine in the urine, combines with the silver. 9. Lead acetate precipitates sulphate of lead, PbS0 4 , phos- phate, Pb 3 (P0 4 ) 2 , and chloride, PbCl 2 , besides other substances. 10. Ferric chloride precipitates, after previously acidulating with acetic acid, phosphate of iron, Fe 2 (P0 4 ) 2 . 11. An ammoniacal solution of cupric oxide is decomposed by boiling by the action of the urates. 12. Tannic acid produces no precipitate with normal urine. (Krukenberg, Grundriss d. Med. Chem. Analyse, 1884.) PART II. CHAPTEK II. NORMAL ELEMENTS OF THE URINE. History of Urea— Description — Physiological Conditions which modify the Amount of Urea — Chemistry — Artificial Production of Urea, etc. — Physical Properties — Combinations with Acids — Extraction and Preparation of Urea — Quantitative Analysis of Urea — Process of Leconte — Process of Millon — Process of Liebig — Volumetric Analysis — Hypobromite Process — Pathological Significance — Uraemia — Medicinal Agents which Influence the Excretion of Urea — Thera- peutic Indications. The normal constituents of the urine are divisible into : (1) Or- ganic Substances, (2) Inorganic Substances, and comprise the following : ORGANIC SUBSTANCES. Urea. Uric acid (urates). Hippuric acid. Creatine and creatinine. Xanthine and hypoxanthine. Oxaluric acid. Allantoine. Succinic acid. Benzoic acid. Oxalic acid (oxalate of lime). Volatile acids (phenols). Colouring matters. INORGANIC SUBSTANCES. Chloride of sodium. ,, of potassium. Sulphuric acid and sulphates. Phosphoric acid and phosphates. Phosphoglyceric acid. Potash, soda, lime, and mag- nesia. Ammoniacal salts. Iron, silica, nitrates and nitrites. Peroxide of hydrogen. Carbonic acid, oxygen and nitrogen. NOKMAL ELEMENTS OF THE URINE. 43 Nitrogenous Constituents (Organic). Urea, Percentage composition. CO(NH 2 ) 2 Carbon 12 Hydrogen 4 Nitrogen 28 Oxy gen 16 12x1=12 1x4= 4 14 x 2=28 16x1=16 20-00 6-66 46-67 26-67 60 = comb. wt. 100-00 History. — This substance, one of the most important con- stituents of the urine, was discovered by Boerhaave prior to 1720, but it seems to have attracted little attention until 1771, when it occurred to the younger Kouelle to extract with spirit of wine the * saponaceous matter ' or syrup obtained by the evaporation of urine. This extract he found to be crystallizable, and con- ceived that it contained hydrochloric acid as an essential in- gredient. Prior to this, Boerhaave succeeded in separating the chloride of sodium and the urea. In 1798 Cruikshank obtained this principle in the form of crystal, but it was not until 1799 that Fourcroy and Vauquelin obtained it in a pure form, and recognised it as the crystallized substance of Rouelle. Berzelius was the first to obtain it in a colourless form by means of oxalic acid, and Prout ultimately established its composition. Description. — Urea is one of the products of the perfect oxida- tion of nitrogenous tissue in the living body. Of the solid con- stituents of the urine it constitutes one half, while a fourth is made up of chloride of sodium. It exists in the urine of all the mammifera, birds, and reptiles, but it is in the urine of car- nivorous animals that it exists in greatest abundance. It is formed in the blood, or, more strictly speaking, it is a product of the interchange of blood constituents with the nitrogenous textures of the body, and it is simply filtered from the system by the kidneys. This is demonstrated by the fact that when struc- tural disorganization of the kidney supervenes on disease (as in Bright's disease), urea and other excrementitious substances accumulate in the blood, and give rise to the form of blood- poisoning termed uraemia. 44 THE URINE IN HEALTH AND DISEASE. In the serous effusions which attend diseases of the kidney and in the sweat a much larger quantity of urea is found than in the normal condition. In cholera, which is attended with sup- pression of the urine and deficient oxidation of tissue, urea, in consequence, is found correspondingly diminished in the blood. No trace of urea is found in the muscular tissue or juice of muscle, but there are other nitrogenous substances representing a lower form of oxidation, such as creatine and xanthine, and from which urea can be produced. That such transformation takes place in the organism is shown when, by introducing such substances as uric acid, allantoine, and creatine into the blood, the quantity of urea is forthwith augmented in the urine. This transformation is effected by means of the oxygen and the alkalies of the blood. Besides existing normally in the urine and in the blood (0*16 per 1,000, Picard), (0*177, Marchand), urea is found in the amniotic fluid, in the chyle, and lymph (2 per 1,000, Wartz), in the saliva (0'36 per 1,000, Picard ; 0*67 to 1 per 1,000, Kabuteau).* According to Eabuteau and Papillon, urea exists in notable quantity in the peritoneal cavity of flat fish under the form of trimethylurea, which, they point out, is decomposed under the influence of alkalies and ammonia into trimethylamine. Alimentation exercises a direct influence over the amount of urea excreted from the body ; for while upon a mixed diet 25 grammes per day may be eliminated (2*5 to 3*2 per cent.), the quantity may be increased to 50 grammes if a highly nitrogenous diet be indulged in. Lehmann found the quantity to amount to as much as 58 grammes in the twenty-four hours on a purely animal diet, and to decrease to 15 grammes on a non-nitro- genous diet. Urea does not disappear from the urine even when no food is taken. So strongly may the urine become im- pregnated with urea, that the mere addition of nitric acid to it, without evaporation, may determine the instant formation of nitrate of urea. The question has been propounded whether it is necessary for the production of urea from nitrogenous principles that they be previously incorporated with the organism. It has been * Comptes Itendus de la Socicte de Biol., 1871, p. 180. NORMAL ELEMENTS OF THE URINE. 45 maintained* that certain nitrogenous principles of food are con- vertible into urea by the system without previous assimilation, just as sulphates and phosphates appear rapidly in the urine after the ingestion of a diet rich in sulphates and phosphates. In this manner it was concluded that a portion of the urea found in the urine is directly traceable to the food. This opinion must be received with reservation, and for the following reasons : Urea is formed by the system even when no food whatever is taken, and its proportion diminishes but very little during the first days of fasting ; it is notably increased by muscular exertion, and it is with much difficulty artificially formed from nitrogenous materials which have been subjected to the physiological processes of the body. Admitting that it does appear in augmented proportion in the urine after food, it seems more reasonable to suppose that the alimentary principles which find their wa} T into the blood give a stimulus to the dis- integration and oxidation of tissue, and that there is an accele- rated circulation attendant on the process of digestion. It seems to me that it is in this relation that the augmented production of urea and alimentation ought to be regarded. In a paper on this subject Dr. Salkowskif remarks that the principal facts are that certain amido-acids, after their ingestion in the alimentary canal, appear in the urine in the form of uramid acids, or combinations of the amido-acids with the group COXH. Secondly, certain other amido-acids, such as glycocoll, leucin, asparaginic acids, which are products of the disintegra- tion of albumen, when administered with the food, lead to augmented excretion of urea, and after the ingestion of sal ammoniac the greater part of the nitrogen appears in the urine as urea. Physiological Conditions which modify the Amount of Urea. — In the condition of health, the amount of urea in the urine varies at different periods of the day, and with the nature and quantity of food and exercise. As we have seen, it is augmented by nitrogenous diet and exercise ; cold baths and intellectual activity (Byasson) are alleged to have a like influence. The * Comptes Rendus de la Socieie de Biol., 1871. p. 180. t Centralblatt, No. 53, 1875. 46 THE UKINE IN HEALTH AND DISEASE. quantity is diminished by repose and a vegetable diet. Kabu- teau* has made the interesting observation that during men- struation the amount of urea is diminished by 20 per cent. The diminution appears two days before the appearance .of the menses, and ceases a few days afterwards. During that time the pulse diminishes in frequency, and the temperature is lowered by about half a degree. This is a most interesting observation in view of the fact that while in man the amount of carbonic acid gas eliminated as he advances in life up to forty or fifty years of age augments, in woman, from the estab- lishment of menstruation to the menopause, the amount of carbonic acid eliminated by the system is not greater than in the girl of fifteen. During twenty days of each month the adult female eliminates much more urea and carbonic acid than the non-menstruating girl. The female who eliminates from 14 to 15 grammes of urea during the period of menstruation elimi- nates from 19 to 20 grammes before menstruation and five or six days after it has ceased. Now, physiological data show that a direct relationship exists between the quantity of blood dis- charged from the system at this period and the amount of carbonic acid and urea formed ; for, as we know, the red- blood corpuscles are the carriers of oxygen ; it is through their agency that the nervous centres are stimulated, and it is by their means, through their ox} 7 gen, that eremacausis is carried on, and carbonic acid and urea produced. Generally speaking, an adult man eliminates in his urine from 18 to 30 grammes per day ; a female, on an average, 25 grammes Some authorities give a higher figure. Neubauer, in the case of an individual on a mixed diet, gives from 22 to 35 grammes, and Beale from 25 to 40 grammes. Mehu gives the low average of from 15 to 20 grammes. Chemistry. Artificial Production of Urea.— To Wohler (1828) is due the credit of having first artificially produced urea. To accomplish this, ammonium sulphate and potassium cyanate are dissolved in water in equivalent proportions, and the solution evaporated to dryness. The following reaction takes place : (NH 4 ) 2 S0 4 +2KCNO=2NH 4 NCO + K 2 S0 4 . * Soc. de Biolog., 1870, pp. 75, 110, and Gaz. Heb. de Med. et de Chir., 1870. NORMAL ELEMENTS OF THE URINE. 47 On boiling the solution of ammonium cyanate a molecular change ensues, the latter becoming converted into isomeric urea, thus : NH 4 NCO=(NH 2 ) 2 CO. Potassium cyanate is easily made by the oxidation of potassium cyanide, and potassium cyanide is obtained by heating potassium ferrocyanide. Thus we have the preparation of urea on a large scale. Take 28 parts of K 4 Fe(CN) 6 and 14 parts of peroxide of manganese (Mn0 2 ), previously well mixed and dried, and subject the mixture to slow combustion. Cyanate of potassium is thus obtained. The mass is treated with cold water, and subsequently decomposed by the addition of 20^ parts of sul- phate of ammonia. The resulting compound is evaporated to dryness in a water-bath. Urea, sulphate of potash, and an excess of ammonium sulphate remain. Absolute alcohol is then added, which dissolves out the urea, leaving the other constituents untouched. By filtering and evaporation the urea is deposited in beautiful crystals of considerable size. This is the best method of preparing urea ; but it may also be prepared by the action of oxychloride of carbon (phosgene gas) on ammonia, (COCl 2 +2NH 3 =CO(NH 2 ) 2 +2HCl) ; of ethyl carbonate on ammonia, (C0 3 (C 2 H 5 ) 2 +2NH 3 =CO(NH 2 ) 2 -f2C 2 H 6 0), and of mercuric oxide on oxamide C 2 0 2 (NH 2 ) 2 +HgO=CO(NH 2 ) 2 +C0 2 +Hg). M. Bechampt has succeeded in producing urea by the oxida- tion with permanganate of potash of certain nitrogenous sub- stances, such as gluten, and these observations are confirmed by Kitter. Urea is also produced by the action of peroxide of lead upon uric acid, and also by the action of alkalies upon alloxan and creatine. Physical Properties. — From an aqueous solution urea crys- tallizes in the form of quadratic prisms with a rectangular terminal plane. From an alcoholic solution the planes are octahedral. It is of colourless appearance, and possesses a fresh odour like that of nitre. It is soluble in an equal weight of cold water, and in a much smaller quantity at a high tem- perature. It is easily soluble in alcohol, sparingly soluble in 48 THE URINE IN HEALTH AND DISEASE. ether, and quite insoluble in oil of turpentine. The crystals polarize with a faintish-blue colour. It possesses a somewhat bitter saline .taste. Urea constitutes a base which gives with most diluted acids well-defined crystalline salts. The principal salts of urea are : Fig. 8.— Crystals of Urea. First, the Nitrate. — When nitric acid is added to a sufficiently concentrated solution of urea, it forms a crystalline precipitate of nitrate of urea — CO(NH 2 ) 2 . HN0 3 . The precipitate presents on microscopic examination a characteristic appearance. The crystals consist of large, yellow, hexagonal, and sometimes rhomboidal laminae, overlapping one another at the angles. If this salt be heated, it decomposes towards a temperature of 140°, giving off carbonic acid and protoxide of nitrogen. It is less soluble in water than urea, and is very little soluble in water impregnated with alcohol or nitric acid. Second, Oxalate of Urea. — Oxalic acid added to a solution of urea acts similarly to nitric acid, and forms a precipitate of oxalate of urea — (CON 2 H 4 ) 2 . H 2 C 2 0 4 . This salt crystallizes in prismatic scales. It is soluble in water, but less soluble than the nitrate. It can be dried up to a heat of 100°, but at 150° it decomposes. Oxalic acid has a greater affinity for urea than nitric acid has, so that when added to a solution of nitrate of urea a precipitate results which is not very soluble in water contain- NORMAL ELEMENTS OF THE URINE. 49 ing nitric acid. If chlorine gas is passed over fused urea, hydrochloric acid and nitrogen are evolved, and there remains a mixture of sal ammoniac and cyanuric acid : 6CO (NH 2 ) 2 + 3C1 2 = 2C 3 H 3 N 3 0 3 + 4NH 4 C1+2HC1 + N 2 . But if a solution of urea be acted upon by a solution of chlorine gas or hypochlorous acid, the decomposition is totally different ; thus : CO(NH a ) a +3ClHO = 3HCl+C0 2 +2H 2 0+N 2 . Hydrochloric acid, carbon dioxide, water, and nitrogen are thus formed. If, instead of free chlorine, an alkaline hypo- chlorite be used, the reaction lis the same, only an alkaline chloride is formed, and the carbonic acid gas is not disengaged, but is retained by an excess of alkali. The more alkaline the medium, the more complete the reaction ; thus : CO(NH 2 ) 2 +3NaC10 = 3NaCl+2H 2 0 + C0. 2 +N 2 . The carbonic acid gas is retained in the form of carbonate of soda, and only nitrogen is given off. Fig. 9. — Crystals of Nitrate of Urea. Bromine and the alkaline hypobromites act in a similar manner, but more energetically. When a solution of urea is mixed with an excess of hypobromite of sodium, the former is rapidly decomposed, and evolves about 90 per cent, of its nitrogen : CO(NH 2 ) 2 +3NaBrO f 2NaOH = 3NaBr+Na 2 C0 3 + 3H 2 0+N 2 . 4 50 THE URINE IN HEALTH AND DISEASE. Heated with a solution of nitrate of silver, urea gives nitrate of ammonia and an insoluble cyanate of silver. From the clinical aspect, it may be observed that with the addition of water urea is transformed into carbonate of ammonia. This reaction is facilitated by heat, but in course of time it takes place at the temperature of the air or of the body : CO(NH 2 ) 2 +2H 2 0 = (NH 4 ) 2 C0 3 . Nitrous acid or nitric acid charged with nitrous vapour very rapidly decomposes urea. This reaction has been interpreted in various manners, but according to the excellent observations of Bojmiond, the urea is decomposed, giving off equal volumes of carbonic acid and nitrogen ; thus with nitrous acid : CO(NH a ) 2 +2HNO a = C0 2 +2N 2 +3H 2 0. On mixing a solution of urea with mercuric nitrate, a white precipitate consisting of CO(NH 2 ) 2 , 2HgO is obtained and nitric acid is set free. If the nitric acid be neutralized by the addi- tion of an alkali or baryta water, the whole of the urea may be thus removed. It is on this reaction that Liebig's process for the estimation of urea is based. Phosphoric acid combines with urea to form a soluble phosphate. This salt has been described and studied by Lehmann, who found it in the urine of the pig. Sulphuric acid does not combine with urea ; neither does uric, hippuric, nor lactic acid. Extraction and Preparation of Urea. — Urea may be extracted from the urine by various processes. The simplest is the method employed by Fourcroy and Vauquelin. This consists in evaporating the urine to a syrupy consistence, and in treating the residue with absolute alcohol. Urea as thus obtained is not, however, in a very pure form, and is difficult of crystallization. This process may be advantageously modified as follows : The alcoholic solution is evaporated, and the residue dissolved in water, filtered, and precipitated by nitric acid. The nitrate of urea thus obtaine 1 is collected, washed with water, and then decomposed by boiling with a solution of either bicarbonate of potash, carbonate of baryta, or carbonate of lead. The mixture is then evaporated and treated with concentrated alcohol, which dissolves the urea alone. This process has the following disadvantages : The NOKMAL ELEMENTS OF THE URINE. 51 nitrate of urea is not entirely insoluble in water, and con- sequently there is always loss. Further, a certain proportion of nitro-muriatic acid is formed with the chlorides of the urine. A better method consists in precipitating the sulphates and phos- phates of the urine by the addition of half its volume of a solu- tion of baryta, filtering, and evaporating to dryness on a sand- bath. The residue is dissolved by absolute alcohol and evaporated. Two crystallizations may be requisite. The urine of the dog is much richer in urea than that of man, and may thus be more conveniently employed for purposes of investigation and experi- ment relating to urea. Quantitative Analysis of Urea.— For few substances have more processes of volumetric analysis been employed than for urea. The following are the simplest and most reliable : First, the process of decomposition by the hypochlorites (Leconte). Second, the process of decomposition by means of nitric acid, on which are based the methods of Millon and Liebig. Third, the process of decomposition by alkaline hypobromites. Process of Ldconte.— We have already seen (vide p. 49) Fig. 10. A, Decomposing flask ; B, Graduated tube for reception of nitrogen, that urea is decomposed by chlorine into water, carbonic acid gas and nitrogen. This decomposition is similarly effected by 52 THE URINE IN HEALTH AND DISEASE. the hypochlorites, e.g. — the hypochlorite of soda. To prepare a solution for this purpose, dissolve 100 grammes of well- powdered ' chloride of lime ' in distilled or recently boiled and cold water ; then dissolve in the filtered fluid 200 grammes of crystal- lized carbonate of soda reduced to powder ; wash the resulting carbonate of lime, and make up to 2 litres. This solution should be preserved in a stoppered bottle. The figure on page 51 represents the apparatus of Leconte. Proceed as follows : Take from 10 to 20 grammes of the urine, which introduce into a flask of a capacity of from 120 to 200 cubic centimetres. Fill the flask with the hypochlorite solution, and close the orifice by means of a cork through which a glass tube communicates with a graduated receiver full of water. Decomposition at once ensues, especially at the summer tempera- ture. It is desirable, however, to apply heat by means of a spirit-lamp. The mixture is raised to the temperature of ebulli- tion, and thus maintained until no more gas is evolved. The carbonic acid is retained in the flask, and nitrogen alone is col- lected in the receiver. On examining the formula of urea it will be found that theoretically 10 centigrammes (0*10) correspond to 37 cubic centimetres* of nitrogen, measured at a temperature of 0° and the normal pressure of 760 millimetres; but Leconte has not been able to obtain more than 34 cubic centimetres by means of the hypochlorite of soda, and this figure (34) is adopted gener- ally as the basis of calculation, though some other authorities maintain that the nitrogen given off* is short of the absolute amount by 6 cubic centimetres. If 34 c.c. of nitrogen be, then, equivalent to 10 centigrammes (0*10) of urea, a simple proportion sum will give the urea corresponding to the volume of nitrogen collected in the receiver. In order to obviate errors which may arise in the * That one decigramme of urea will yield at a temperature of 0° and a pressure of 760 mill. 37 c.c. of nitrogen is evident from the following : 1 litre of nitrogen at 0° 760 m.m. = 1*2562 grms. Combining weight of urea = 60. Then, if 60 give 28 N by weight, what will 0'1 of urea give? (60 : 0*1 :: 28 : # = 0*046) — and, of course, 1 grm. of urea gives 0*46, or ten times as much as the decigramme. Now, 1 litre of nitrogen (1,000 c.c.) at 0° 760 m.m. =1*2562 grins. ; hence 1*2562 grms. : 0*46 grm. :: 1,000 : x = 371*48 c.c. nitrogen, and a decigramme 37*1 c.c. NOKMAL ELEMENTS OF THE UEINE. 53 course of this experiment from the presence of albumen and uric acid which may be partially decomposed by the chlorine, and thus evolve nitrogen, the urine ought previously to be purified as follows : To 20 grammes of urine, 3 grammes of subacetate of lead are added. The fluid is boiled, filtered, and the residue well washed ; then 3 grammes of crystallized carbonate of soda are added. This fluid is in turn boiled, filtered and the residue washed. As the volume of the fluid has been augmented by the washings, the half, which represents 10 grammes of urine, is sufficient for the purpose of experiment. Process of Millon. — This process is based on the decomposi- tion of urea by a solution of nitrate of mercury charged with nitrous vapour. Thus : 2CO (NH 2 ) 2 +N 2 0 3 +2HN0 3 = 2C0 2 +2N 2 +H 3 0+2NH 4 N0 3 . The nitric acid is here employed in the form of a nitrate and nitrite of mercury, with an excess of nitric acid. The reagent is prepared by dissolving 125 grammes of mercury in 168 grammes of nitric acid of a density of 1*44, and then diluting with twice the volume of water. Equal volumes of carbonic acid gas and nitrogen are given off. It is with the former alone that the process of Millon deals, and its amount is thus estimated : This gas is received in a tube containing a portion of caustic potash. Prior to the commencement of the experiment this tube is carefully weighed in a chemical balance. Subsequently the two gases pass over the caustic potash, but the carbonic acid gas alone is absorbed, and its weight is represented by the additional weight of the tube. This increased weight multiplied by 1*3636* gives the weight of urea contained in the specimen of urine operated on. Twenty grammes of urine should be introduced into a flask having a capacity of 200 cubic centimetres, and 50 cubic centimetres of the reagent of Millon should be employed. Process of Liebig. — This process consists in the successive employment of a solution of baryta, which separates the sul- phates and phosphates of the urine ; a solution of nitrate of * Combining weight of urea, 60 ; carbonic acid 44 .*. 60 -f 44 = 1*3636 ; hence C0 2 x T3636 = urea in the *20 grammes of urine submitted to analysis. ■ 54 THE URINE IN HEALTH AND DISEASE. mercury, which decomposes the urea ; and a solution of carbonate of soda, which indicates when the reaction is complete. The solution of nitrate of mercury is so prepared that 1 cubic centi- metre of it corresponds to 1 centigramme (0*01) of urea. The mercuric nitrate decomposes the chlorides into sodic nitrate, potassic nitrate and mercuric chloride, and then combines with urea as under. The precipitate varies in composition, according to the degree of concentration of the fluid. The composition is represented by one of the three following formulae : HN0 3 Ur-f2HgO HN0 3 Ur+3HgO HN0 3 + Ur+4HgO In a solution of chloride of sodium containing urea, a per- manent precipitate of urea and oxide of mercury is not formed by a solution of the nitrate of mercury until the whole of the chloride of sodium present has been decomposed and the nitrate thus converted into corrosive sublimate. Immediately on the chloride of sodium being thus decomposed, the next drop of the solution of mercury throws down a permanent deposit of oxide of mercury and urea, which is insoluble in water. Preparation of Liebigs Standard Solution.— Dissolve in strong nitric acid by aid of heat 77*2 grammes (1,196*6 grains) of dry oxide of mercury, so pure that on being heated on a platinum spatula no residue is left. Evaporate the solution to the con- sistence of a syrup, and then dilute up to 1,000 c.c. with distilled water. If any precipitate of basic salt form, add a few more drops of nitric acid. One c.c. of this solution is equal to 0*01 gramme (0*15 grain) of urea. Baryta Solution. — Mix 1 part of cold saturated solution of nitrate of baryta with 2 parts of a cold saturated solution of caustic baryta, and reduce the mixture to half its strength by addition of an equal amount of distilled water. Carbonate of Soda Solution. — A saturated solution, or about 1 gramme to 30 grammes of water, or 20 grains in 1 ounce of water. Dr. Harley has suggested for convenience the impreg- nating of white filter paper with the soda solution. The paper may be cut into strips of convenient size, and preserved in NORMAL ELEMENTS OF THE URINE. 55 a wide -mouthed stoppered bottle. A drop of the mixture to which a sufficient quantity of the nitrate of mercury has been added will stain this paper yellow (oxide of mercury). Volumetric Analysis. — With a graduated pipette, take, for example, 40 c.c. of the urine to be examined, to which add 20 c.c. of the baryta solution. Stir the resulting mixture, and filter. Of this liquid take 15 c.c, which obviously correspond to 10 c.c. of urine, and add a few drops of nitric acid. Place these 15 c.c. of the mixture in a glass flask or glass beaker, and to this quantity add drop by drop the nitrate of mercury solution. The first drops produce no precipitate, as they form with the chlorides of the urine a soluble bichloride of mercury. The chlorides having thus entered into a new combination, the next addition of the nitrate of mercury solution causes a permanent precipitate of urea and oxide of mercury (1 equivalent of the former to 2 equivalents of the latter, or more, according to concentration). The quantity of the nitrate of mercury solution necessary for the saturation of the chlorides is carefully noted, and sub- tracted from the total required to be added until a drop of the solution gives a yellow colour in contact with a drop of the solution of the carbonate of soda. The yellow colour does not appear with the carbonate of soda solution until 1 volume of the solution of mercury, containing 77 parts of the oxide has been added to every 10 parts of urea — that is, 4 equivalents of the mercury to 1 of urea.* If a bluish colour result with the soda solution, it is indicated that there is still free urea in the solution ; a yellow colour (HgO — ' yellow wash '), that there is no free urea, but that there is an excess of the nitrate of mercury. Every cubic centimetre or every fractional part of the mercurial solution required for the second part of the experiment corresponds to a centigramme (0*01), or a corresponding fractional part of urea. The amount of urea in 10 c.c. being thus ascertained, it is a question of simple proportion to determine the daily excretion of urea. Thus, sup- posing that 1 c.c. of the solution was required to saturate the * Theoretically, 100 parts of urea should require 720 parts of mercuric oxide, but the solution must be in excess to give the yellow colour. 56 THE URINE IN HEALTH AND DISEASE. chlorides, and that altogether 19 c.c. were used before the yellow coloration with the carbonate of soda solution was distinctly produced, then : 19 —1 = 18 = 18 centigrammes of urea (0*18). If the patient passed in24hou«rs 1,850 c.c. of urine, then 10 : 1,850 :: 18 : # = 3,330 centigrammes, or divided by 100 = 33*30 grammes. By another process the chlorides may be separated from the urine by a standard solution of nitrate of silver, of which 1 c.c. corresponds to a centigramme of chloride of sodium. To prepare this solution, take of Pure recrystallized nitrate of silver, 29*075 grammes : Distilled water to 1,000 c.c. Let 10 c.c. be taken, and the amount of chloride of sodium be determined by the silver solution, as by the method for determi- nation of chlorides (vide infra). If it is found that 15 c.c. ara required for this purpose, 0*15 centigrammes of sodium chloride are indicated. Then take 30 c.c. (containing 20 c.c. of urine) of the filtrate from the mixture of baryta fluid and urine, add a drop or two of nitric acid. Then if 10 require 15 of the silver solution, 20 must require 30. This should precipitate all the chlorides, which can now be removed by filtration. Additional Corrections. — The mercury solution is graduated for a solution of urea which contains 2 per cent, of urea ; hence 30 c.c. of the mercury solution are required for the complete precipitation of the urea in 15 c.c. of the urea solution. The mixture thus amounts to 45 c.c, in which there are 30 times 5*2 = 156 milligrammes of free oxide of mercury ; every c.c, there- fore, contains 3*47 milligrammes of oxide of mercury. If the 15 c.c of urea solution contain 4 per cent, of urea, and we add 60 of the mercurial solution, a mixture amounting to 75 c.c. is pro- duced, in which there are 312 milligrammes of the oxide of mercury (60x5*2), or 4*16 milligrammes in every c.c, being, therefore, an excess of 0*69 milligrammes (4*16— 3*47) of oxide in every cubic centimetre above what is required to produce the final reaction with carbonate of soda. It is, therefore, clear that in experimenting on urine containing a larger amount of urea than 2 per cent., the urea will appear smaller than it really is. If the urine, as in the example given, contain 4 per cent., we should not add 60 c.c, but only 59*37 c.c. of the mercury solution. NOEMAL ELEMENTS OF THE UKINE. 57 To avoid this error, as soon as it is found that the percentage of urea is higher than that for which the mercurial solution is graduated, add for every additional c.c. of this solution required a half of water before testing with the carbonate of soda. If, for ex- ample, we have used 20 c.c. more than 30, we add 10 c.c. of water. Modification when the Urea sinks below 1 per cent.— Should the quantity of the urea in the urine amount to only 1 per cent., we must add to 15 c.c. of urine, not 15 c.c. of the mercury solution, but 15*3 before the final test-point is reached. In consequence of this source of error, the amount of urea obtained is too great. In operating, then, on dilute urine, for every 5 c.c. of the mercury solution less than 30 which has been used, subtract 0*1 c.c. from the total amount employed. If, thus, for 15 c.c. of urine 25*0 c.c. of mercurial solution have been used, the real amount of urea, being 249 milligrammes, is ex- pressed by 24*9 c.c. of mercurial solution. The Urine contains Albumen. — In this case 50 c.c. of the urine are treated with 2 drops of strong acetic acid, and boiled to coagulate the albumen ; the precipitate is allowed to settle, and 30 c.c. of the clear urine are mixed with 15 c.c. of the baryta solution, filtered, and treated as already described. Liebig's process is thus a troublesome one, subject to errors requiring correction, and for simplicity and accuracy is of inferior value to one or other of the methods of determining the amount of urea by the alkaline hypobromites. Volumetric Analysis of Urea by Hypobromite Process. — This process is based upon the fact that hypobromous acid decomposes urea into carbonic acid, water and nitrogen. The decomposition is as follows : CO(NH 2 ) 2 + 3NaBrO - 3NaBr + C0 2 -r-2H 2 0 +N 2 . In this process the volume of nitrogen disengaged is the measure of urea. The hypobromite solution is best prepared by dissolving 100 grammes (3 J ounces) of common caustic soda in 250 c.c. (9 ounces) of water, and when cold* adding 25 c.c. (7 drachms) of bromine. * This is a necessary precaution, for unless the bromine be added to the soda solution when perfectly cold, the proper amount of nitrogen is not evolved when the experiment is conducted. 58 THE URINE IN HEALTH AND DISEASE. We have already seen (vide footnote, p. 52) that 1 gramme of urea yields 0*46 gramme of nitrogen by weight, and occupies a volume of 371*48 c.c.* at 0° and 760 m.m. It therefore follows that every cubic centimetre of nitrogen evolved, after a given quantity of urine is treated with the hypobromite solution, represents a corresponding fractional part of a gramme of urea. Supposing the tube for the recep- tion of the nitrogen to be graduated into cubic centi- metres, and that 37 '1 c.c. of nitrogen are evolved, it follows that this represents the tenth part of a gramme or Ol of urea. In this calculation the normal temperature and pressure are assumed. While 37*1 c.c. is absolutely the correct number, Leconte has never been able to obtain more than { « 34 c.c. of nitrogen from a decigramme of urea, and g consequently 34 is usually adopted, especially in o France, as the basis of calculation, and as being equivalent to Ol of urea at 0° and 760 m.m. There- in fore, supposing 25 c.c. of nitrogen have been evolved § f rom the urine experimented upon : |x 34 c.c. : 25 :: 0*1 : # = *073 gramme of urea. [ It will be obvious that, to ascertain the quantity rH of urea passed in twenty-four hours, it will be 2 necessary to know the volume of urine passed in ^ twenty-four hours, and of the urine operated upon. With a view to obviate the necessary corrections for temperature and pressure, Yvon has suggested the employment of this instrument. It consists of a glass tube of 40 centimetres in length. Towards its upper extremity it is traversed by a stop-cock, on either side of which the tube is graduated into tenths of a c.c. The instrument is inserted into a long narrow tube containing mercury, the stop-cock is opened, and the lower portion of it is thus filled with the mercury. The stop-cock is then closed and the instrument raised, and supported in the tube by means of * 371-48 c.c. N 2 : 1 c.c. N 2 :: 1 gr. : x = '002689 gr. urea. NORMAL ELEMENTS OF THE URINE. 59 Fig. 12. — Gerrard's Ureometer.* — This in- strument consists of two tubes of unequal diameter and length, and connected by a piece of indiarubber tubing. The longer tube is filled from the shorter with water, and is gradu- ated for the estimation of the nitrogen received from a bottle also connected with it by indiarubber tubing, and in which the decom- position of the urine takes place by means of the hypo- bromite solution. The top of the measuring- tube is connected with a tube of indiarubber, which may be closed by a clamp. Method of Using. — Pour into a test-tube 5 c.c. of the urine to be examined, and in the bottle (a) 25 c.c, or six fluid drachms, of sodium hypobromite solu- tion. Place the tube carefully inside the bottle, as shown on the illustration, taking care to avoid any spilling of the contents. Pill the glass tube (b c) with water, so that the level reaches the zero line, taking care that when this is done the tube (c) contains only a little water by being placed high — it having to receive what is displaced from (c) by the nitrogen evolved. The clamp at the top of the long tube having been open to relieve pressure, this is now shut. Then connect the indiarubber tubing to the bottle, note that the water is exactly at zero, and upset the contents of the test-tube into the hypo- bromite solution. Nitrogen is evolved, which depresses the water in (b). When this ceases, lower the tube (c) until the level of the water in both tubes is equal. The tube is graduated in per cents, of urea, and cooling for five or ten minutes should be allowed to take place before the readings are taken. The solution of hypobromite of soda is made by dissolving 100 grammes of caustic soda in 250 c.c. of water, and when cold 22 c.c. of bromine are added. To obviate the disagree- able smell and dangers of the bromine vapour, the bromine can be obtained in hermetically-sealed glass tubes containing 2 c.c. One of these, placed in the large bottle with 25 c.c. of the soda solution, gives, when broken with a sharp shake, the exact quantity of hypobromite for one estimation of urea. * Manufactured by Gibbs, Cuxson and Co., Wednesbury. 60 THE URINE IN HEALTH AND DISEASE. the arm of an ordinary stand. A kind of mercurial barometer is thus formed, into the chamber of which it is possible to introduce fluids without the admixture of air. A standard solution of urea is first prepared, containing 1 centigramme (O01) in 5 c.c, and this is measured in the upper Tig. 13. — Ukeometer of Dobemus.* — This simple instrument, originally designed by Dr. Charles Doremus, of New York, gives fairly accurate results. Directions for Use. — Fill the vertical tube with a solution of hypobromite of sodium, by pouring the solution into the bulb until it is about half full. The apparatus should then be inclined horizontally until the entire tube is filled, about one-third being left in the bulb. Then restore the apparatus to the vertical position. Draw into the pipette 1 c.c. of the urine to be tested, pass the pipette into the apparatus, the point being placed immediately under the long arm. Compress the indiarubber cap plowly, and the gas which is liberated will thus pass up the long tube. It now collects in the upper part of the tube, and its volume being read off, indicates the amount of urea from which it has been evolved. In cases where there is much urea, it is advisable to mix the urine with an equal amount of water before testing. In this case the result will be equal to one-half of that indicated on the scale. Each division of the instrument indicates •001 gramme of urea in 1 c.c. of urine. The percentage of urea is obtained by multiplying the result of the test by 100. To ascertain the total amount of urea voided in twenty-four hours, multiply the result by the number of c.c. of urine parsed during that period. The instrument is also graduated to the English scale, each division indi- cating one grain of urea per fluid ounce of urine. part of the tube, which is correspondingly graduated. Turning the stop-cock, the fluid descends into the lower portion of the tube, and the mercury descends correspondingly. The tube is then washed with a small quantity of a solution of caustic soda, which is mixed with the urea solution. Then from 5 to 6 c.c. of the hypobromite solution are introduced into the upper part of * Manufactured by Southall Bros, and Barclay, Birmingham. NORMAL ELEMENTS OF THE URINE. 61 the tube, communication with the lower part being meantime shut off. By turning the stop-cock admixture of the fluids takes place, and reaction immediately commences, but no gas escapes, the pressure being more feeble inside than outside. To facilitate the admixture of the fluids, the thumb is placed on the lower portion of the tube and the instrument shaken. It is now re- Fig. 14. — Ureometer of Noel. Mode of Uaing. — Fill the gauge E with water to within one or two centimetres below the zero mark of the graduated jar C. Then pour 15 c.c. of hypobromite solution into the tube H, and 2 c.c. of urine into the small graduated tube U, and about 2 c.c. of a saccharine solution. Establish the connections. Note that the level of the water in C is at zero. Incline the tube H. When the evolution of the gas has ceased read off the amount of nitrogen in the graduated tube C. placed in the receiving -tube until such time as the evolution of all the nitrogen has taken place. The fluid then becomes of a yellow colour, and the operation is terminated. The instrument is now introduced into a tube full of water, when the more dense hypobromite solution flows out, leaving the gas, the amount of which is read off. This operation demonstrates that under 62 THE URINE IN HEALTH AND DISEASE. the conditions in which the experiment is conducted a given quantity of nitrogen is evolved. Under the same conditions a Fig. 15. — Noel's Ureometer Modified by Mehcier. In this apparatus the tube E is filled with mercury instead of water, so that any error from solubility of the nitrogen in the water is obviated. C. Tube for reception of the nitrogen divided into one- tenth c.c. ; E, Tube containing mercury ; T, Empty tube ; U, gradu- ated urine-tube. NORMAL ELEMENTS OF THE UB1NE. 63 certain quantity of urine will give a relative amount of nitrogen gas. This comparison obviates the troublesome corrections as to temperature and pressure, the conditions being identical. Therefore, if 1 centigramme of urea register 40 divisions of nitrogen or 4 c.c, and if a c.c. of urine give 88 divisions, then 40 : 88 :: 1 : x = 2 centig. 2 mill, or 22 grammes per litre. Another source of error is further obviated by this process, viz., that arising from the fact that the hypobromite does not separate more than about 92 per cent, of the nitrogen, or about the same relative percentage between the theoretically correct number, 37 c.c, which a decigramme of urea ought to yield, and the 34 which practically Leconte found it to yield. Yvon used another ureometer, in which water takes the place of mercury, but as the principle is the same the process need not be here described. Should the urine be found to be rich in urea, it may be diluted with twice or four times its volume of water, and the result multiplied accordingly. Hypobromite of soda not only decomposes urea, but it like- wise decomposes creatine, creatinine, uric acid, and the urates. In very exact analysis allowance must be made for this. In order to eliminate the error in connection with the urates the following procedure should be adopted : Take 10 c.c. of urine, to which add 1 c.c. of a solution of subacetate of lead, then sufficient water to make up to 5 c.c, and filter. The urates are separated in the stats of urate of lead, and the excess of lead in the solution does not prevent the decomposition of urea by the hypobromite of soda. The oxide of lead at first formed is dis- solved in the alkaline fluid. The excess of subacetate of lead may be removed by carbonate of soda. For this purpose take 10 c.c of urine in a graduated tube, and add a solution of car- bonate of soda to make up to 50 c.c, shake, and filter. The urine is thus obtained free from lead. Speaking generally, an augmentation of nitrogen to an extent of 4*5 per cent, may be allowed as arising from other sources than urea, and for clinical purposes it will be sufficient to subtract 4 per cent, from the amount of nitrogen obtained. Hence, if 64 THE URINE IN HEALTH AND DISEASE. 1 centigramme of urea = say, 39 divisions of N, 1 cubic centimetre of urine = 68 ,, then 39 : 68 :: 0*01 : £=0'01743 and per litre 17'43 grammes, then 100 : 17-43 :: 4-5 : ^ = 0*78 and 17'43 gr. - 0*78 = 16*65 gr., which represents very nearly the quantity of urea contained in a litre. M. Mehu has made the very interesting and important ob- servation that with urine containing glucose the hypobromite separates all the nitrogen contained in the urea. Hence, in conducting a volumetric analysis of urea, a watery solution of glucose may be used, instead of distilled water for diluting the urine. Pathological Significance. — Urea represents the complete oxidation of the nitrogenous tissue of the body, and probably to some extent the transformation of nitrogenous constituents of food. It will follow that the amount of urea excreted will be in a direct ratio to the amount of tissue disintegration, and bear consequently a relative proportion to the combustion and temperature of the body. It is, therefore, notably increased in all febrile affections, in inflammations (such as pleurisy, pneumonia, meningitis), in eruptive fevers, in acute articular rheumatism, phthisis, etc. In typhus fever and pneumonia from 50 to 60, or even 80, grammes (double that of health) may be excreted during the twenty-four hours. Increase of urea in febrile affections is of graver import when the ingestion of nitrogenous matter is reduced to a minimum. As the fever abates its excretion diminishes, and the diminution is maintained by the small amount of food usually taken, or the impaired functional activity of the digestive organs. With recurring appetite and strength the amount of urea again increases. In intermittent fever the urea is considerably augmented during the accession of the fever, and Ringer and Chalet have made the notable observation that the urea is in excess before the thermometer indicates an elevation of temperature. In typhoid fever Parkes found as much as 57 grammes (883*5 grains) in the urin of NORMAL ELEMENTS OF THE URINE. 65 twenty-four hours, and Vogel in one case the large amount of 78 grammes (1,209 grains). According to Sigmund,* the urea is augmented from the commencement of typhoid fever. In jaundice, according to Bouchardat, the urea is considerably increased. In two severe cases of this disease, on the third and fourth day he found from 59 to 133 grammes of urea in twenty-four hours' urine. In a case of chronic cerebritis, Dr. Harley found the proportion as high as 57*42 grammes (890 grains), and as the patient recovered it fell to 46*5 grammes (720*7 grains), and still later to 37*1 grammes (574 grains), in twenty-four hours. In a case of pyaemia, Vogel found 80 grammes (1,240 grains) of urea. In diabetes the amount is greatly increased. Dr. Harley has found as large an amount as 70 grammes (1,085 grains) in the twenty-four hours' urine of a gentleman of nearly fifty years of age. The same authority states that the average of twenty-nine analyses of diabetic urine yielded 47 grammes (723*5 grains) — a quantity greatly in excess of the normal amount. To some extent he believed this to be due to a rich animal diet. In certain eruptive fevers the amount of urea is likewise augmented. Andral found in a case of urticaria with intense fever 30 per 1,000. In diabetes the amount of urea excreted per diem is augmented, though the percentage amount is diminished owing to the large quantity of urine secreted. Durante has observed a similar augmentation in varicella and erysipelas of the face. The Amount of Urea is diminished, conversely, when tissue metamorphosis is retarded, and there is deficient oxidation of tissue ; thus, in anaemia, with deficient red corpuscles, and consequently deficient oxidation, pulmonary emphysema, heart affections, cholera, uraemia, scorbutus, Addison's disease, etc. Thudichum states that the lowest amount of urea he has observed to be discharged by a patient during twenty-four hours was 5 grammes in 75 c.c. of pale, faintly alkaline urine. The patient was a lady suffering from anaemia, and an abdominal tumour caused by an accumulation of faeces which had escaped through an ulcerated portion of the intestine. * Archiv.fiir Physiol, unci Pathol. Ch. unci Mic. (Vienna, 1852) 5 66 THE URINE IN HEALTH AND DISEASE. According to Parkes, uric acid can always be found in the blood after all nitrogenous food is cut off ; and this is held by some to be fatal to the theory of deficient oxidation as the cause of an excess of uric acid. It is quite possible that all the urea is not derived from the uric acid, and that under any circumstances Fig. 16.— Ureometer oe Regnard. E K, Receiver of gas ; A, Bulb for the urine ; B, Bulb for the reagent ; /, Glass tube to diminish pressure. Mode of Using. — Into the bulb A place 2 c.c. of the urine to be examined ; into B about 10 c.c. of the hypobromite solution. Estab- lish the connections. The level of the water should be identical in K and in the gauge E. This is accomplished by lowering or raising the glass tube (I). Incline the tube so that the two liquids may come in contact, when nitrogen is evolved and the result may be read off. some of it must exist in the blood, and that thus no excess of oxygen would cause it entirely to disappear. Doubtless the other intermediate products, such as creatin and leucin and indican, contribute to the formation of urea. The fundamental prin- ciples of physiology point to oxidation as the process by which all the ultimate excreta are formed, and urea can be no exception. NORMAL ELEMENTS OF THE URINE. 67 In Addison's disease, while the amount of urea is diminished, the amount of indican is greatly augmented. Bosenstein,"* in two cases of this nature, found that the urea diminished to from 20 to 12 grammes, while the normal quantity of indican in- creased tenfold. In a case of cancer of the liver, Hirne found the proportion of urea as low as from 6 to 7 grammes in 700 grammes of urine. In cholera, where the coldness of the body and general collapse indicate an arrest of the vital functions and diminished oxidation of tissue, there is a notable diminution of urea and other extractive matters of a lower form of oxida- tion. In a case of this description Desnos and Chalvet found but traces of urea with 4 per 1,000 extractive matter. In the blood of the same patient urea existed in the proportion of 3*6 per 1,000, and extractive matter 19 per 1,000. During the period of reaction the patient eliminated 700 grammes of urine in twenty - four hours, and the urea amounted to 28*8 per 1,000, and the extractive matter to 22. It is inferred that the collapse in this disease may be due to the retention in the blood, to some extent, of the urea and extractive matter, and that the conditions may have some etiological relationship with uraemia. The sweats which supervene in cholera during the period of reaction contain, as well as the urine, a large quantity of urea, which had been retained in the blood by the ischuria. On spontaneous evapora- tion of the cutaneous transudation, a white crystalline powder of urea forms. In dropsy the proportion of urea in the urine is notably diminished; but it is contained in the fluid effused into the various cavities and tissues of the body. In these cases, under the influence of diuretics, urea appears in large quantity in the urine. Urea is found in the fluid of hydrocele to the extent of 25*62 grm. per litre ; and in dropsy the blood may be found to contain 0*365 grm. per litre, against 0*18 to 0 20, the normal quantity. In uraemia, that the diminution of urea is due to deficient oxidationf of tissue is shown by the greatly diminished temperature of the body. It is not clear, nor even probable, that the symptoms of uraemia are exclusively due to the retention of urea in the blood, but rather to other excremen- * Revue des Sciences Med., 1873, and Virchow's Archiv., Bd. lvi. t Vide 'Lectures on Bright' s Disease,' by Author (Churchills). 68 THE URINE IN HEALTH AND DISEASE. titious elements which have not yet been isolated. Urea maybe injected with impunity, in considerable doses, into the blood. In certain cases of albuminuria it is well known that there is a con- siderable diminution of urea. This seems to be due to arrested elimination, as well as to deficient formation. Into the latter question we cannot enter here, but on the former it may be remarked that this is characteristic of the ' small red granular kidney.'* In this condition we have large hyaline tube casts in the urine, which indicate that the convoluted tubes have been denuded of their epithelium, whose special function it is to separate the urinary solids ; and hence we have a low specific gravity of urine (1010 to 1005), and urea and extractive matter accumulating in the blood. Uraemia. — MM. Grehant and Quinquand have returned to the investigation of this subject by experimenting on animals. Subcutaneous injections of aqueous solutions of pure urea were employed in gradually increasing quantities on frogs, guinea-pigs, rabbits, pigeons and dogs. The result was constant for the different kinds of animals, and consisted in a more or less rapid death from tetanic convulsions, similar to those produced by strychnia. The most numerous experiments were performed on dogs. The toxic dose of urea in the blood was fixed with exacti- tude, and the influence of urea on muscular contractility was studied. Death always ensued when a dog received into its system 10 grammes of urea for every kilogramme of body weight. The proportion of urea in the blood, as estimated just before or after death, was 0*6 gramme for every 100 grammes of blood, and this relative proportion obtained in all other animals employed. In a case of azuria in a man, the proportion was •410 per 100 grammes, and in another case of retention of urine •278 ; in a case of interstitial nephritis, the patient suffering from uraemic dyspnoea, it was *210, and in a case of uraemic coma *215. Under the circumstances of the experiments all the tissues of the animals were impregnated with urea, so that 100 grammes of blood yielded 613 milligrammes of urea ; 100 grammes of liver, 580 milligrammes ; 100 grammes of cardiac tissue, 311 milli- grammes ; 100 grammes of spleen, 662 milligrammes. The * Vide 1 Lectures on B right's Disease,' by Author (Churchill's). NORMAL ELEMENTS OF THE URINE. 69 observers always noticed that the urea injected under the skin was never completely absorbed, even at the time of death, though death might have been delayed for ten hours. They also found that urgemia does not increase nor diminish muscular contrac- tility. The blood of dead animals, when submitted to distillation at a temperature of 40° C. in vacuo, furnished a liquid absolutely free from ammonia ; the conclusion drawn from the experiment is that urea does not act as ammonic carbonate. On the whole, it appears that leucomaines, ptomaines and other extractives participate in the production of uraemia. Medicinal Agents which influence the Excretion of Urea. — The medicinal agents which influence the excretion of urea are divisible into two groups, viz , those which increase, and those which diminish, the amount of urea. These substances may be thus tabulated : Medicinal Agents which in- Medicinal Agents which di- crease the Amount of Urea. minish the Amount of Urea. Urea itself. Digitalis. Uric acid. Alcohol. Common salt. Coffee. [ f Phosphoric acid. Tea. J Squill. Iodide of potassium and Glycin. sodium. Leucin. Bromide of potassium. Theobromine. Arsenic. Colchicum.* Turpentine. Cubebs. Nitrate of potash and soda. Atropine. Alkaline carbonates. Cantharides. Mercury. Vegetable acids. Antipyrin. Ferruginous preparations. Valerian. Hypophosphite of soda. Sulphate of quinine. Chloride of potassium. Benzoic acid. Chloride of ammonium. Coca. Permanganate of potash. Large quantities of water. Oxygen. * Vide Author's ' Observations on Therapeutics and Disease ' (Churchills). t 1 Aliments d'epargne.' 70 THE UKINE IN HEALTH AND DISEASE. Therapeutic Indications. — If an excessive excretion of urea indicate a preternatural disintegration of nitrogenous tissue, and the system appear to suffer thereby, then a diet rich in nitrogen is indicated, such as animal soups, eggs, milk, etc., and one or other of the moderators of disintegration above tabulated. In health a farinaceous diet, such as arrowroot, sago, tapioca, etc., will diminish the amount of urea. Should it appear that too little urea is formed by the system, then exercise ought to be enjoined in order that more oxygen may be inhaled, and one of the group of exciters of metamorphosis administered, such as preparations of iron, common salt, permanganate of potash, etc. Carbon ... Hydrogen Nitrogen Oxygen ... Water . . . UKIC ACID. C 5 H 4 N 4 0 3 = 168. 33-714 1-191 33-333 19-048 10-714 100-000 Natural State — Extraction and Preparation of Uric Acid — Properties of Uric Acid — Urates— Acid Sodium Urate — Acid Potassium Urate — Acid Ammonium Urate — Acid Calcium Urate — Acid Magnesium Urate— Lithium Urate — Tests for Uric Acid — Quantita- tive Estimation of Uric Acid — Uric Acid in Albuminous Urine — Extraction of Uric Acid from Calculi and Sediments — Physio- logical Relations of Uric Acid — Pathology of Uric Acid — Therapeutic Indications. Natural State. — After urea, uric acid is the most important normal element of the urine. It is found in all animals, even the lowest in the scale. Griffiths has found it in the green gland of the cray-fish ; and MacMunn in the Malpighian tubes of insects and the nephridia of snails. Mettlebach found from 8 to 45 milligrammes of uric acid per 100 c.c. of urine in oxen. The statement is therefore inaccurate that it is absent in the urine of herbivorous animals, and is here replaced by hippuric acid. The urine of birds contains a largo (mantity of uric acid, NOEMAL ELEMENTS OF THE URINE. 71 and that of serpents is almost entirely composed of pure uric acid. The urine of man contains a few decigrammes per diem. The blood contains it to a like amount, and here the proportion is largely augmented in cases of gout. It is likewise in all probability the materies morbi of rheumatism; and everything points to its being a product of suboxidation, as arising from an excessive proteid dietary, alcoholic and vinous indulgences, sedentary habits, and all such conditions as retard eremacausis, either directly or indirectly. It is found either free or as urate of soda in the articular concretions of gout and in calculi. In conformity with what has been just remarked, it is reduced in amount* by active exercise in the open air, by the inhalation of oxygen, by lime-juice, alkaline carbonates, and vegetable acids (which are in the system converted into carbonates), by large doses of quinine, by common salt, by salicylates and benzoates of soda, salts of lithium, and notably by colchicum, by which it is converted into urea. It may be obtained for purposes of study from guano, or the excrement of serpents, from uric acid calculi, or from urine. Extraction and Preparation.— Uric acid exists in the urine especially in the form of an alkaline urate. It is sometimes spontaneously deposited, in consequence of the reactions which accompany the cooling of urine ; it is then more or less coloured. In order to extract uric acid from urine, about 20 c.c. of hydro- chloric acid are added to a litre of urine, and the fluid is filtered. The urates are thus decomposed. The filtrate being allowed to stand for twenty-four hours, a precipitate of uric acid is found to have deposited on the bottom of the vessel. The precipitate is less coloured than that which spontaneously deposits in the urine ; still, it presents the appearance of cayenne pepper. In order to obtain crystals in a state of purity, the crystals obtained as above are dissolved in sulphuric acid, and then precipitated with water, when small characteristic crystals of great whiteness are obtained. If the urine be of low specific gravity, it is well to concentrate it by evaporation before treatment with the hytho- chloric acid. * Vide ' Observations on Therapeutie3 and Disease,' by D. Campbell Black, M.D., etc. (J. and A. Churchill). 72 THE URINE IN HEALTH AND DISEASE. Properties of Uric Acid. — Thus prepared, uric acid is found to be a weak dibasic acid, which furnishes both acid and neutral salts. The neutral salts are more soluble than its acid salts. It presents the appearance of light scales, soft to the touch, and of a great variety of forms of crystallization. The rhombic form, with two obtuse angles, is the predominating crystalline form of uric acid. These crystals are often designated the 1 lozenge ' form of uric acid. A ' dumb-bell ' form is also described, which frequently exists in sediments. It is well to note that oxalate and carbonate Fig. 17. — Typical forms ok Ukic Acid Crystals. of lime present the same form of crystallization. Few substances present a greater variety of forms than uric acid. This acid has neither taste nor odour, and it does not redden litmus. It is very insoluble in water, requiring from 1,800 to 1,900 times its weight of cold water, and 1,400 to 1,500 of boiling water, to dissolve it. It is insoluble in alcohol and in ether. It dissolves easily in a solution of phosphate of soda, in lixed alkalies, in carbonates, phosphates, and borates of the fixed alkalies, but not in the corresponding ammoniacal salts. It dissolves with difficulty in ammonia. Sulphuric acid dissolves it without decomposition, and it may be precipitated therefrom by the addition of water. Nitric acid dissolves it, but decomposes it in so doing. A ♦ NORMAL ELEMENTS OP THE URINE. 73 potassic solution of uric acid reduces Fehling's solution, and may thus be confounded with glucose. Heated in a tube, uric acid decomposes into urea and cyanuric acid. It forms at the same time hydrocyanic acid and carbonate of ammonia. Boiled with acetate of lead, uric acid is decomposed into carbonic acid> allantoi?ie, ttrea, and oxalic acid. Fig. 18.— Rarer Forms of Uric Acid Crystals. If one part of uric acid be treated with four parts of con- centrated nitric acid, there is decomposition with effervescence, and the liquid solidifies. The following represents the decom- position which takes place : 2C 5 H 4 N 4 0 3 + 2H 2 0 + 0 2 =2C 4 H 2 N 2 0 4 +2CO(NH 2 ) 2 . uric acid alloxan urea Uric acid may be decomposed by carbonic acid, a fact which accounts for the presence of acid urates, and their deposition in the urine. Alloxan which originates as above is remarkable for the beautiful red coloration which it gives with ammoniacal vapour. This is due to the formation of iso-alloxanate of ammonia which characterizes uric acid (murexide reaction).* By the action of caustic potash this coloration changes to purple - * From murex, a shell- fish of similar tint. 74 THE UEINE IN HEALTH AND DISEASE. blue. All the urates give the rnurexide reaction. As with uric acid, the urates do not affect litmus. Urates. — Uric acid forms with alkalies two series of salts — viz., the neutral urates and the acid urates, which are much more soluble than the free acid, and dissolve more easily in a hot than in a cold solution. Further, the neutral salts are more soluble than the acid salts ; neutral urates of potassium and lithium are the most soluble, and acid urate of ammonia the least soluble. When hydrochloric or acetic acid is added to urine for the purpose of decomposing the urates, the uric acid separates in a crystalline form ; and if the fluid is concentrated this takes place immediately, but if diluted a considerable interval will elapse before precipitation. Uric acid, being very insoluble in water, does not exist normally in the urine as such, but is always found in combina- tion in the form of acid sodium urate, acid potassium urate, acid ammonium urate, and, under rare circumstances, acid calcium urate. Acid sodium urate (C 5 H 3 NaN 4 0 3 ). — This constitutes the most common urate deposit, and presents a rose-colour when Fig. 19.— Groups of Acicular Crystals and Spherical Masses of Sodium Urate. it deposits in urine which has become cool. It is rendered soluble by the least elevation of temperature. Acid urate of sodium is soluble in about 1,200 parts of cold water, and in 125 NORMAL ELEMENTS OF THE URINE. 75 parts of boiling water. Under the microscope, it presents the appearance of spherical granules, which are more frequently in clusters than singly. With nitric acid and ammonia, this salt gives the murexide reaction, and calcination leaves a residue of carbonate of soda. Acid Potassium Urate (C 5 H 3 KN 4 03). — This urate is almost always found in combination with that of soda, and is more soluble in water. One gramme dissolves in 800 parts of water at 15° C, and in 75 of boiling water. It leaves on calcination a residue of carbonate of potash. Acid Ammonium Urate (C 5 H 3 (NH 4 )N40 3 ). — This urate is in- variably found in urine which has become ammoniacal. It is very insoluble, 1 part requiring 1,600 parts of water for its solution. It leaves no residue on calcination. It is distinguish- able from uric acid by the evolution of ammonia when heated with caustic soda. It presents the appearance of spheres, more or less voluminous, sometimes spiney. Two spheres are some- times united by a peduncle, and thus present a dumb-bell appearance. Fig. 20. — Ammonium Urate. Acid Calcium Urate. — This form of urate is found much more rarely in the urine. It is frequently found in calculi. On calcination it leaves a residue of carbonate of lime. It is very insoluble in water. It effervesces with acids, and gives in solution the reaction of the salts of lime. Acid Magnesium Urate is sometimes found in the urine 76 THE UKINE IN HEALTH AND DISEASE. under similar circumstances. In solution it gives with acids the reactions of magnesium salts. Urate of Lithium, the most soluble of all the urates, is sometimes found in urine. It dissolves in 116 times its weight of water at 39° C, and in 367 parts of water at 20° C. The salts of lithium are thus used therapeutically as eiiminants of uric acid.* In winter, owing to the cold, urates are found most frequently in the urine. When the urine is very acid, from containing a large proportion of acid phosphates, these appropriate from the neutral urates a portion of their base, and thus transform them into acid urates, which being less soluble than the neutral, are precipitated. Indeed, the acid phosphates may remove the whole of the base, and thus precipitate free uric acid. Hence the formation of deposits of urates and uric acid during the first period of the decomposition of urine on exposure to air. When heated, all the urates dissolve, and also on addition of caustic soda or potash, and when treated with acids they yield uric acid crystals. Corresponding to these acid urates, there are the normal urates of ammonium, sodium, potassium, calcium, and lithium. Being much more soluble than the acid urates, they remain in solution when precipitation of the latter takes place. The formation of carbonic acid in the urine may occasion the change from neutral to acid urates thus : 2C 5 ,H 2 ,Na 2 ,N 4 O 3 +H 2 0 + CO 2 =2C 5 ,H3.NaN 4 ,O 3 -fNa 2 ,CO3. normal sodium urate acid sodium urate Tests for Uric Acid. — Uric acid is recognisable by its characteristic microscopic appearances. If but a small quantity of fluid be available, from 2 to 3 grammes are placed in a test-tube with two or three drops of a solution of glacial acetic acid, a piece of linen of from 3 to 4 c.c. in length is immersed in it, and the fluid is allowed to repose in a cool place for about twenty-four hours. The uric acid is found to * Saturation of the urine with ammonium chloride precipitates all the urates. The murexide test can then be applied, and the quantity of uric acid in a given specimen of urine can thus be estimated by weighing. NORMAL ELEMENTS OF THE URINE. 77 have deposited on the linen, and the microscopic examination may then be made. It may also be separated by evaporating a small quantity of urine to dryness in a water-bath, any albumen having been previously removed. The residue is then treated with alcohol, to remove the urea and other constituents soluble therein. Then the fluid is treated with weak hydrochloric acid to remove the salts, and the uric acid alone remains. The result of microscopic examination may be confirmed by chemical tests. Thus, in a small porcelain capsule a little of the sediment, or of the residue obtained as above, is placed, and moistened with a drop or two of nitric acid. The uric acid dissolves with effervescence, giving off reddish vapours. Moderate heat is then applied to volatilize the excess of acid, a reddish- coloured residue being the result, and one or two drops of a solu- tion of ammonia added (1 gramme of ammonia to 9 grammes of water), when a purple coloration is obtained, which constitutes the murexide test (ammonium purpurate — C 8 H 4 (NH 4 )N 5 0 6 ). The same result is obtained by exposure to ammoniacal vapour. The addition of caustic potash or soda causes a violet-blue colora- tion. According to Magnier de la Source, the reaction may be better accomplished in the following manner : Instead of employing nitric acid, a few drops of bromine water (5 or 6 drops of bromine to 100 c.c. of water) are added to the residue operated on, and the whole evaporated on a water-bath. The ammonia is then added, when a purple coloration, which on the addition of potash passes into a violet-blue, is the result. These tests are of extreme delicacy. Scliijfs Test. — A little of the residue is dissolved in sodium carbonate, and a drop of the solution is then placed on a piece of filter-paper, previously moistened with a solution of nitrate of silver, when a brownish stain is produced, due to deposition of metallic silver. Bosenberg's Beaction. — If an equal volume of a solution of phosphotungstic acid be added to urine, with a drop of caustic potash, soda, or ammonia, a blue coloration, due to the presence of uric acid, results (Pharm. Centralhalle, xxxi., 1890). Beaction of Dietrich. — If a little uric acid solution be added to 78 THE URINE IN HEALTH AND DISEASE. an iodized solution of hypochlorite of sodium a rose coloration is produced, which disappears if the sodium solution be in excess. If an alkaline solution of uric acid or of urates be heated with the liquor of Barriswell,* a white precipitate of urate of copper and a red precipitate of urate of copper (cuprosum) result. This precipitate must not be confounded with the precipitate similarly caused by glucose. If a solution of uric acid in caustic soda be boiled with a small amount of Fehling's reagent, a grayish precipitate of urate of cuprous oxide is obtained. Should the copper salt be in excess, a red cuprous oxide is the result. Quantitative Estimation of Uric Acid. — Empirically, a rough estimate of the amount of uric acid in urine may be obtained by multiplying the two last figures of the density by 2, when the result would express in centigrammes the quantity of uric acid per litre. While the process is somewhat trouble- some, weighing alone gives the most accurate quantitative results. For this purpose the acid is precipitated as above by hydrochloric acid, and collected after sufficient repose in a cool place. One hundred c.c. of filtered urine (any albumen having been removed) are placed in a porcelain capsule, and 3 to 4 per cent, of hydrochloric acid added ; after from twenty-four t© thirty hours' repose the crystals are collected on a filter, whose tare has been obtained. The uric acid is washed with distilled water, which process is continued until the wash-water is no longer acid. The uric acid is then to be washed with alcohol to remove hippuric acid and any accidental colouring matters. It is then dried at a temperature of 100° C. until it ceases to lose weight ; from the final weighing the weight of the filter is deducted, the result being the weight of uric acid. Uric acid is not absolutely insoluble in water, nor in water acidulated with hydrochloric acid. Hence to obtain perfect accuracy of result, an allowance must be made for the portion dissolved by adding 0'0045 grm. for each c.c. of water employed in washing. Haycraft's Method.— This process requires (1) a centinormal * Cupro-potassic liquor. NORMAL ELEMENTS OF THE URINE. 79 solution of sulpho cyanide of potassium, to obtain which 8 grammes of this salt are dissolved in a litre of water : 1 c.c. two = 0*00168 of uric acid ; (2) a decinormal solution of nitrate of silver ; (3) a saturated solution of iron alum ; (4) a 20 to 30 per cent, solution of nitric acid; (5) a solution of ammonia; and (6) an ammoniacal solution of nitrate of silver, to obtain which 5 grammes of nitrate of silver are dissolved in 100 c.c. of water, a sufficiency of ammonia being added to produce a limpid solu- tion. Process. — To 25 c.c. of urine containing no albumen add 1 gramme of sodium bicarbonate, and from 2 to 3 c.c. of the ammoniacal solution ; then add from 1 to 2 c.c. of the silver solution, in order to precipitate the uric acid as urate of silver. Wash the precipitate with distilled water in order to remove the excess of the soluble silver salt ; dissolve the precipitate in a few c.c. of nitric acid solution, and precipitate the silver with the solution of sulphocyanide of potassium, the iron alum serving as an indicator, the number of c.c. of y|ro of the sulphocyanide solution, multiplied by 0*00168 gramme, indicating the quantity of uric acid. This process is based on the precipitation of uric acid in a state of urate of silver, insoluble in ammonia and soluble in nitric acid. Hay craft attributes the irregularity of the com- position of urate of silver, as indicated by Salkowski, in part to the precipitation of ammonio-phosphate of magnesium, and in part to the reduction of the silver, which varies with time and temperature. Salkowski-Ludwig Method. — If an ammoniacal solution of nitrate of silver be added to a solution of uric acid, to which has been previously added an ammoniacal mixture of chloride of magnesium and of chloride of ammonium, the uric acid is precipitated as a magnesio-silver salt. This is collected, washed, and decomposed by either sodium or potassium hydrosulphide, when the uric acid again passes into solution as a urate of the alkali. When an excess of hydrochloric acid is added to this solution, the urate is decomposed; the uric acid is separated out, and may thus be collected and weighed. Process of Bayrac. — Of the nitrogenous compounds of the 80 THE URINE IN HEALTH AND DISEASE. urine, urea, uric acid, and creatinine are alone decomposed by hypobromite of soda, evolving their nitrogen incompletely in the cold; and completely on being heated. The other nitro- genous constituents exist in urine in so small an amount as not to merit consideration. The principle of this process consists in separating the uric acid from the two other nitrogenous con- stituents by means of alcohol, and in acting on the isolated principle, by means of a concentrated solution of hypobromite of soda, at a temperature of from 90° to 100° C. Fifty c.c. of urine are concentrated on a water-bath, the uric acid precipitated by 5 c.c. or 10 c.c. of dilute hydrochloric acid, and washed with alcohol. This removes the creatinine, and the urea, leaving the uric acid ; the acid is then dissolved on a water-bath by 20 drops of caustic soda, and treated with 15 c.c. of a concentrated solution of hypobromite of soda, at a temperature of from 90° to 100° C. {Journal de Pharmacie et de Chimic, xxi., 1890, p. 611). Of other processes for the quantitative analysis of uric acid may be mentioned those of Arth* and Butte. f Uric Acid in Albuminous Urine.— When the urine con- tains albumen, as hydrochloric acid precipitates this body, it is necessary to employ a 6 per cent, solution of phosphoric acid, or an equal volume of glacial acetic acid, which pre- cipitates the uric acid to the exclusion of the albumen. In the case of a more or less considerable quantity of urine, the albumen may be coagulated by heat, and thus separated by pouring on a filter. The filtrate, plus the water employed to wash the albumen coagulum, being mixed and concentrated if necessary, the amount of uric acid may be determined in the ordinary manner. If a precipitate of urate or of free acid has already formed in a vessel, it must be vigorously agitated, and be rapidly poured into another vessel, a few drops of caustic soda being added to cause solution, and then the whole is filtered ; the filtered liquid, being exactly measured, is employed for the determination of the uric acid and the albumen. Instead of the soda solution * Comp. Rend, de VAcad. des Sciences, February 17, 1890. f Repertoire de Pharmacie^ 1890, p. 38. NORMAL ELEMENTS OF THE URINE. 81 a gentle heat, not sufficient to coagulate the albumen, may be employed to dissolve the urate deposit. Extraction of Uric Acid from Calculi and Sediments. — The calculi or sediments, finely pulverized, are dissolved in caustic potash, and after filtration the solution is acidified with hydrochloric acid. The uric acid is again dissolved in caustic potash and reprecipitated by the acid, until the product obtained be sufficiently pure. Instead of treating the potash solution with hydrochloric acid, M. Mehu advises the passing of a current of carbonic acid gas through the solution, whereby the free alkali becomes a carbonate, while the uric acid is deposited in the condition of a urate of potash. This deposit may be then collected, carefully washed, and decomposed by hydrochloric acid. Physiological Eelations of Uric Acid.— In common with urea, uric acid results from the metamorphosis of proteid elements in the economy ; but it is not an ultimate product of combustion, for when introduced into the system it undergoes further com- bustion, forming urea. The quantity of uric acid eliminated in twenty-four hours is much less than that of urea, varying from 0*30 gramme to 0*80 gramme, or an average of 0*55 gramme, or about one-tenth of the solid matters of the urine. This average varies according to circumstances. A proteid diet augments the amount of uric acid, while a non-nitrogenous dietary causes a diminution. A diminution also appears after indulgence in copious draughts. The greater portion of the uric acid is contained in the urine in the form of an alkaline urate ; sometimes the urine contains uric acid in a free state, which separates either after emission of the urine, owing to acid fermentation, or in the bladder. In all quantitative analyses of uric acid, the entire urine of twenty-four hours must be operated upon, owing to the feeble solubility of the acid. When the proportion of uric acid in the body may be quite normal, a very little diminution in the urinary secretion may suffice to cause an abundant precipitation. Pathology of Uric Acid. — Uric acid is excreted in augmented amount in all febrile affections, accompanied by embarrassment of respiration, such as pleurisy, pericarditis, capillary bronchitis, 6 82 THE UEINE IN HEALTH AND DISEASE. chronic emphysema, etc., there being obviously in these circum- stances a deficiency of oxidation. The same thing obtains in laucocythaemia, pernicious anaemia, and in the constitutional condition termed the uric acid diathesis, the cause being evidently the same. The blood being poor in iron, the organic combustion is less perfect. In the uric acid diathesis the acid separates in the urinary passages, and is eliminated with the urine in the form of little reddish particles, known as uric acid gravel. In cases of articular rheumatism, 0 the amount of uric acid is augmented during the period of greatest intensity of the fever, and diminishes during its decline. Its amount is also diminished in chronic rheumatism. It forms concretions of urate of soda in the joints in gout ; and before the attack its excretion is very feeble, while after the attack it augments, and finally diminishes. In chronic gout a diminution is observed. In cases of obesity and diabetes there is a diminution of uric acid. In a certain form of glycosuria, described by Bouchard as glycojwlyuric diabetes, there is, on the contrary, a consider- able augmentation of this body, amounting to as much as 3 grammes per diem, during which period the sugar diminishes in quantity or totally disappears. In cases of interstitial nephritis, where there is desquamation of the cells of the convoluted tubes, there is, for obvious reasons, a diminished amount of uric acid. The same obtains in grave cases of scarlet fever. In cases of typhoid fever the appearance of uric acid or of urates in the urine has been held as indicating a period of crisis. According to Bouchard, in cases of lead-poisoning the proportion of uric acid is diminished to about a half. Haig maintains that its presence in the blood augments vascular tension. Therapeutic Indications. — If an excess of uric acid represent an imperfect oxidation of proteidsin 11 ie body, and the full oxida- tion be represented by urea, then the dietary should be regulated accordingly, and the medicinal agents administered should be such as stimulate and augment eremacausis. Nitrogenous diet should be restricted, and vegetable and farinaceous diet be enjoined. Sulphate of quinine diminishes uric acid, as likewise bicarbonates, alkaline carbonates, and vegetable acids (which arc * Vide Author's 1 Observations on Therapeutics and Disease.' NORMAL ELEMENTS OF THE URINE. 83 converted in the system into carbonates), and all of which act as energetic oxidizing agents. Common salt, sulphate, carbonate, salicylate, and benzoate of soda, and inhalations of oxygen* act in a similar manner. The administration of colchicum is indicated, for there is sufficient scientific testimony to its augmenting the amount of urea by diminishing and transforming uric acid, which it appears to effect in the liver. The salts of lithium cause the speedy disappearance of uric acid,f and piperazine is said to possess a similar property. HIPPURIC ACID. Hippuric Acid (C 9 ,H 9 N0 3 ) is found especially in the urine of the herbivora, as the horse, the ox, etc. In the urine of the carnivora, and especially in that of man, it exists in but a very minute quantity. It occurs here, however, after the inges- tion of certain vegetables, such as asparagus, plums, whortle- berries, brambles, and generally a purely vegetable diet, and from the use of benzoic acid, cinnamic acid, essence of bitter almonds, quinine and analogous bodies. Its presence has been de- monstrated in the urine of new-born infants for some days after birth. Some authors maintain its existence in the blood, in the suprarenal capsules, * Vide Author's 1 Observations on Therapeutics and Disease.' j Lithium carbonate dissolves in 200 parts of boiling water. With an equal wt ight of uric acid half that quantity of water will suffice even at the temperature of the b-idy. The uric acid eliminates car- bonic a'iid from the carb nate. Salts of lithium are consequently pre- scribed in cases of gout and the uric acid diathesis. (a Fig. 21. — Hippuric Acid. Rhombic prisms ; (b) needle form. 84 THE URINE IN HEALTH AND DISEASE. and the sweat, but this is doubtful. In the urine, hippuric acid is found as a hippurate of soda or potash (urine of the horse). It is not probable that it exists in a free state in the urine in even the feeblest proportion. Hippuric acid is colourless, odour- less, and of a slightly bitter taste ; it crystallizes in the form of rhomboidal prisms, with pyramidal ends, and sometimes in the form of fine needles. These crystals are frequently arranged in groups, and present a semi-transparent or milky appearance. They dissolve in 600 parts of cold water, and in a much smaller amount of boiling water. They are easily soluble in alcohol and insoluble in petroleum-ether, and may be thus separated from benzoic acid, which is soluble in this reagent. Solutions of hippuric acid strongly redden litmus paper. Hippuric acid, when feebly heated in a test-tube, is transformed into an oily fluid, which solidifies on cooling ; at a higher temperature the mass becomes red, and evolves benzoic acid and an agreeable odour of hay, ultimately becoming of the odour of hydrocyanic acid. When it is evaporated with concentrated nitric acid it evolves an odour of nitro-benzene. Hippuric acid is monobasic and forms salts, with the exception of its iron salts, which are freely soluble in water. When boiled with con- centrated mineral acids, or heated for a long time with water at a temperature of 170° to 180° C, it is resolved into benzoic acid and glycocoll. When it undergoes the alkaline fermentation under the influence of the Micrococcus ureal, the same change ensues. Hence it is not found in putrid urine, where its place is taken by benzoic acid, which is one of the products of the change. It is formed in the body by the union of benzoic acid with glycin (glycocoll). Extraction. — To extract hippuric acid, the following is the most convenient process: Concentrate on a water-bath to an eighth of its volume a portion of the fresh urine of a horse ; add hydrochloric acid, and after a period of repose the hippuric acid separates in fine needles. It is preferable, however, to saturate the fresh urine with lime-water, which transforms the hippuric into a salt of lime ; the fluid is then filtered, evaporated to a syrupy consistence, and decomposed by hydrochloric acid. Cazeneuve recommends that a litre of urine be evaporated to a NOEMAL ELEMENTS OF THE URINE. 85 tenth of its volume, or 100 grammes, and then mixed with 200 grammes of ' plaster ' (CaC0 3 ) and 20 grammes of alum, and dried on a water-bath. The alum, whose reaction is acid, decom- poses the carbonates and sets the hippuric acid at liberty. The mixture is then placed in a digester and acted upon by boiling ether, which dissolves out the benzoic acid and fatty matter, and leaves crystals of hippuric acid of great brilliancy. It is easily traced in the urine after the administration of benzoic acid. Tests and Quantitative Analysis.— Submit the crystals obtained as above to microscopic examination, and in confirma- tion effect the above-mentioned reactions. Its quantity can be determined by weighing the crystals. Meissner advises that a kilogramme of fresh urine be operated on ; add to it a solution of baryta until a precipitate is obtained, filter, and to the filtered fluid add drop by drop dilute sulphuric acid, so as to leave no trace of baryta. Care must be taken not to add an excess of sulphuric acid. Filter anew, and exactly neutralize with hydrochloric acid ; evaporate on a water-bath to the consistency of a thick syrup ; pour into a wide -mouthed vessel containing 200 c.c. of absolute alcohol. The succinates and the chloride of sodium precipitate, and the hippuric acid remains in solution. After agitation and prolonged repose, re- filter, and evaporate the alcohol on a water-bath ; the residue is again placed in a wide-mouthed bottle, and treated with hydro- chloric acid and about 125 grammes of slightly alcoholized sulphuric ether. On being agitated the hippuric acid is set free, dissolving in the ether, and may be precipitated by evaporation, and then dried and weighed.* Physiology and Pathology. — Hippuric acid is found in normal human urine in very small quantities — 0*30 gramme to 1 gramme in twenty-four hours. Its amount varies according to alimenta- tion. After the ingestion of benzoic acid its amount is aug- mented ; on a flesh dietary, even, it may appear in the urine, being derived in this case from the decomposition of proteids. The change from benzoic acid into hippuric seems to be effected * One or two drops of a neutral solution of ferric chloride give a light red precipitate with hippuric acid. 86 THE URINE IN HEALTH AND DISEASE. by the cells of the convoluted tubes.* According to Salomon, after the excision of the kidneys in rabbits and injection of benzoic acid into the blood, hippuric acid could be detected in the blood, muscles, and liver ; on the other hand, in diseases of the kidneys, it was found that benzoic acid was no longer capable of being transformed into hippuric acid. It is stated that even in excised kidneys the injection of benzoic acid is followed by the appearance of hippuric acid in the blood which flows from the organ. It is said to be augmented in the urine in diabetes and chorea. Creatine and Creatinine. Creatine (C 4 H y N 3 0 2 )t exists normally in muscular tissue, both striated and unstriated, to the extent of 2 per cent. The urine does not normally contain creatine, that which is found in it originating in the transformation of creatinine. The physio- logical role of creatine is undetermined. It does not seem to act as an aliment, inasmuch as it too speedily transforms into excrementitial bodies, such as urea, creatinine, and sarcosine (C 8 H 7 N0 2 ). jo Fig. 22. — Creatine. Creatine occurs as rhomboidal, colourless, and very brilliant prisms. It has a sharp, bitter taste, and dissolves in 75 parts of cold water, in 9410 parts of alcohol, and not at all in ether. The solution has no action on vegetable colours, and evaporation transforms the creatine into creatinine. This transformation * Vide Beaunis's 'Physiology,' v^J. i., p. 282. t Methyl-guanidine acetic acid. NORMAL ELEMENTS OF THE URINE. 87 takes place rapidly in presence of concentrated acids, the r 3 suit being the loss of two molecules of water : Creatine. Creatinine. C 4 H 9 N 3 0 2 - H 2 0 = C 4 H 7 N 3 0. With chloride of zinc, concentrated solutions give a crystalline precipitate of chloride of zinc and creatine. When boiled with caustic alkalies and water, creatine is transformed into urea and sarcosine, the former being in great part in turn decomposed into carbonate of ammonia. Dilute mineral acids dissolve creatine without decomposing it, and crystallizable salts are thus obtained. At the boiling-point it reduces the salts of mercury. Extraction. — A portion of beef is minced and treated with one and a half its volume of alcohol at 90° C. ; it is then heated in a closed vessel on a water-bath. The same process is re- peated, with a fresh portion of alcohol. The two alcoholic liquids are united, the fluid passed through linen, and the alcohol removed by distillation. The residue of the distillation is then diluted with water and treated with an excess of acetate of lead, and the precipitate which forms is removed by nitration and rejected. The excess of lead is removed by a current of sulphuretted hydrogen ; and after a second nitration, to separate the sulphide of lead, the fluid is evaporated in a water-bath to the consistency of a syrup. After some hours' standing in a cool place crystals of creatine are deposited. These may be purified by boiling in water with animal charcoal, filtrated, and crystallized. Instead of minced beef, \ Liebig's Extract ' may be used, and the subsequent processes followed out as above. The quantitative analysis of creatine is made by weighing. By prolonged boiling, creatine reduces Fehling's solution without any separation of cuprous oxide ; and on boiling with an alkaline mercuric oxide, a transient red colour is obtained, and ultimately there is a separation of metallic mercury. Creatinine (C 4 H 7 N 3 0).— This substance, discovered by Liebig in the urine, is a powerful non- volatile, animal base. It dis- places ammonia from its salts. It forms prismatic, colour- less, and very brilliant crystals ; soluble in 11 parts of cold water, 100 parts of absolute alcohol, being still more soluble in THE URINE IN HEALTH AND DISEASE. these media when heated. Creatinine is but very sparingly soluble in ether. Its solutions are feebly alkaline ; with mineral acids it forms crystals, which are freely soluble. When concen- trated urine is treated with chloride of zinc, two double chlorides are formed — viz., a chloride of zinc and creatine, and a chloride of zinc and creatinine. Creatinine exists in the urine to the extent of 0*5 to 4*9 grammes per diem. Fig. 23.— Creatinine. The chloride of zinc and creatinine — (C 4 H 7 N a O),2ZnCL 2 — dis- solves sparingly in cold water ; it is more easily soluble in boiling water, and is insoluble in alcohol. The creatinine may be thus isolated. Nitrate of silver, bichloride, and nitrate of binoxide of mercury precipitate solutions of creatinine. In alkaline solutions creatinine is slowly transformed into creatine ; heat favours this change, which spontaneously takes place if a solution of creatinine be abandoned for a month or two. Fig. 24.— Double Chloride or Zinc and Creatinine. Extraction. — In order to extract creatinine from the urine, 300 c.c. of urine are precipitated with a mixture of lime-water and of chloride of calcium ; if the urine be albuminous, the albumen must be removed by coagulation, and if it contain sugar, this must be destroyed by fermentation. The liquid is to be concentrated to a syrupy consistence, and from 40 to 50 c.c. NORMAL ELEMENTS OF THE URINE. 89 of alcohol are to be added at a temperature of 95° C. After standing for eight hours, the liquid is filtered and washed with a little alcohol. If the solution occupy a volume of more than 60 c.c, it is to be concentrated in a water-bath ; on cooling, one- half a c.c. of a saturated solution of chloride of zinc is to be added, the fluid agitated, and allowed to stand for two or three days, at the end of which time creatinine is deposited on the walls of the vessel. In order to isolate the creatinine, the double salt is to be dissolved in boiling water, and then boiled during a quarter of an hour with hydrated oxide of lead. Decolorize the solution with animal charcoal and evaporate to dryness. The residue consists of a mixture of creatine and creatinine. Treated with alcohol, the creatinine is dissolved and the creatine left behind. On evaporating the alcoholic solution, the crea- tinine deposits in beautiful crystals ; and the creatine may be obtained by crystallizing from boiling water, or instead of extracting the creatinine from the urine, it may be obtained by the transformation of creatine. For this purpose the creatine is to be heated for about an hour with hydrochloric acid on a water-bath ; evaporate so as to remove as much as possible of the free acid, when chlorhydrate of creatinine crystallizes. Finally, these crystals are dissolved in about three or four times their weight of water, and decomposed by boiling with oxide of lead ; chloride of lead is formed, and the creatinine is set free. Tests. — The presence of creatinine is demonstrated by Weyl's test. Mix a few drops of a dilute solution of nitro-prussiate of soda and a few drops of diluted caustic soda with the urine ; the liquid assumes a beautiful ruby colour, which soon passes to yellow. If after decoloration a little acetic acid be added, a greenish-blue colour is produced. The presence of albumen in the urine does not prevent this reaction, and it is not caused by any other of the constituents of the urine. If the urine be of too deep a colour, this reaction fails. In this case it is necessary to isolate the creatinine in a pure state by the formation of a chloride of zinc and creatinine as above, and then submit the solution of one or other of these to the action of the nitro- prussiate of soda and the solution of soda. Creatinine may be recognised in the urine by its crystalline form. Creatinine 90 THE URINE IN HEALTH AND DISEASE. reduces Fehling's solution, and it gives a yellow crystalline precipitate when heated with a dilute solution of phosphomolybdic acid, being previously acidified with nitric acid. It renders red litmus blue, and nitrate of silver and bichloride of mercury precipitate it. Quantitative Analysis. — The crystals of chloride of zinc and creatinine which precipitate as above are collected on a tared filter, washed with alcohol, and dried at 100° C. Let_p represent the quantity of chloride of zinc and creatinine obtained from 300 c.c. of urine, then i 9 X^~ = «r, or the amount of creatinine con- tamed in the same volume. In order to obtain the weight of creatinine per litre, divide the result a? by 3, and then multiply by 10. Physiology and Pathology.— A healthy individual on a mixed dietary eliminates, on an average, 1 gramme of creatinine in twenty-four hours, or, according to Neubauer, 0*60 to 1*20. A highly nitrogenous diet augments the proportion. It is also augmented in acute febrile diseases, as in pneumonia, typhoid fever, intermittent fever, tetanus, etc. It diminishes, on the contrary, during convalescence from these diseases, and like- wise in anaemia, chlorosis, muscular atrophy, tuberculosis, paralysis, etc. Xanthine and Hypoxan- tiiine. Xanthine (C5H4N4O2) exists but in very small quantity in normal urine (1 gramme in 800 litres). It is found throughout the entire organism. Scherer has found it in the spleen, the pancreas, and the brain. It is found in certain forms of It is increased in the urine in Fig. 25. — Hydrochloratk and Nitrate of Xanthine. urinary calculi of rare form, leucocytheemia. NORMAL ELEMENTS OF THE URINE. 91 It appears in the form of a white waxy body, sparingly soluble in water, and insoluble in alcohol and in ether. It is soluble in ammonia, potash, and caustic soda. With hydrochloric and nitric acid it forms crystalline salts. It is precipitated from its ammoniacal solution by chloride of zinc, chloride of calcium, and acetate of lead, and from a hot aqueous solution by acetate of copper and binoxide of mercury. If xanthine be evaporated with nitric acid, a yellow residue is obtained, which on addition of potash becomes of a yellowish red when cold, and of a violet red on being heated. When a particle of xanthine is deposited on a mixture of caustic soda and a little chloride of lime, it encircles itself with a deep green zone, which soon passes into brown and disappears. Hypoxanthine (C 5 H 4 N 4 0), or Sarcine, is not regarded as a normal constituent of urine. It is a body closely resembling xanthine, and is found in different organs of the body, such as the liver, the spleen, and pancreas, and sometimes in the urine in cases of leucocythaemia. Hypoxanthine is changed into xanthine by oxidation. When evaporated with nitric acid, hypo- xanthine gives a yellow stain, which, on addition of caustic soda, does not become reddish-yellow. Oxaluric Acid. Oxaluric Acid (C 3 H 4 N 2 0 4 ). — This acid constitutes one of the derivatives of uric acid, and its presence has been demonstrated in normal urine. According to Schunck and Neubauer, it exists in small portions in the urine in the condition of an ammoniacal salt, and exhibits the form of a fine crystalline powder of acid taste, and very insoluble in water. Oxalurate of ammonia is, on the contrary, very soluble in water. It crystallizes in the form of long prismatic crystals united together in tufts or rosettes. Allantoine. Allantoine (C 4 H 6 N 4 0 3 ) is a characteristic constituent of the liquor amnii. It is found in the urine after the internal administration of uric acid, in fcetal urine, and in the urine of 92 THE UKINE IN HEALTH AND DISEASE. Fig. 26. — Allantotne. newborn children, in which it may continue for some days. It crystallizes in transparent, rhomboidal, colourless prisms, which are soluble in 160 parts of cold water, more soluble in boiling water and alcohol, and insoluble in cold alcohol or ether. Succinic Acid. Succinic Acid (C 4 H 6 0 4 ) has been found in normal urine by Meissner and Shepard. When benzoic acid is ingested its quantity is augmented. Succinic acid crystallizes in hexagonal tables, which are odourless and colourless, and remain unchanged in the air. One hundred parts of water dissolve 5*14 grammes at a temperature of 15° C, and at a temperature of 100° C. 100 grammes of water dissolve 120 of acid. It is not very soluble in alcohol, and less so in ether. With alkalies it forms soluble combinations. Extraction. — Precipitate the urine with baryta, eliminate the baryta with an excess of sulphuric acid, and evaporate. Then acidify strongly with a concentrated solution of sul- phuric acid, and agitate with ether. Eliminate the ether by distillation, treat the residue with water, heat to ebullition, and during the process add drop by drop pure nitric aeid until the liquid presents a permanent yellow colour. After concentration of the liquid, succinic acid separates in a crystalline form. The nitric acid destroys all the impurities without attacking the succinic acid. Fig. 27.— Succinic Am> NORMAL ELEMENTS OF THE UBINE. 93 Tests. — An aqueous solution of succinic acid accurately neutralized by an alkali gives, with perchloride of iron, a reddish precipitate, which is insoluble in mineral acids. A fragment of succinic acid heated in a test-tube evolves white vapours of a nature irritating to the tracheal mucous membrane. The solution, or that of its combination with potash or soda, gives a white precipitate with alcohol. Benzoic Acid. Benzoic Acid (HC 7 H 5 0 2 ) is not a normal constituent of urine, but is found in it during putrefaction, being derived from hippuric acid. It is found in the urine after the ingestion of benzoic acid, or of substances which are transformed in the organism into this acid, such as cinnamon, benzoin balsam, balsam of tolu, quinine, prunes, etc. Benzoic acid crystallizes in the form of fine colourless needles or brilliant scales. It sublimes at 240° C. without de- composition, and is very soluble in ether. It is difficult of solution in cold water, but dissolves more readily in boiling water. Alcohol, ether, acetic acid, and petroleum-ether dissolve it readily. Its solutions redden litmus, and with alkalies it forms salts soluble in water and in alcohol. Extraction. — In order to extract it from the urine, the liquid is concentrated to the consistence of an extract, and then treated with alcohol. The alcohol is removed by evaporation, and the aqueous residue is treated with hydrochloric acid, where- upon the benzoic acid separates. Oxalic Acid. Oxalic Acid — Oxalate of Lime (C 2 H 2 0 4 +2H 2 0).— The most important of the non -nitrogenous organic acids of the urine is oxalic acid. It is frequently found in the urine, but only in small quantity, amounting to about 2 grammes in twenty -four Fjg. 28. — Benzoic Acid. 94 THE UKINE IN HEALTH AND DISEASE. hours. It is found under the form of oxalate of lime, in which combination it forms the greater part of the ' mulberry calculus.' It crystallizes in rhomboidal colourless crystals, soluble in water and in alcohol. Oxalate of lime forms small square, brilliant, octahedral crystals, which are perfectly transparent, strongly refract light, and present the appearance of an ordinary letter envelope. At other times it presents a lozenge form, or that of a triangle with terminal pyramids, and is not unfrequently found in the ' dumb- bell ' form. Oxalate of lime is insoluble in water, sparingly soluble in acetic acid, but is easily soluble in hydrochloric and nitric acid. It also dissolves in acid phosphate of soda, which accounts for its being found in solution in the urine. Detection and Isolation from Urine.— Mix from 400 to 3 i._Tripie Phosphates (Phos- with the ammonia, and phates of Ammonia and Magnesia). being precipitated under the form of ammomo-phosphate of magnesium. It is thus that the earthy phosphates are fre- quently observed in the urine under pathologi- cal conditions. As the urine always contains at the same time phos- phate of calcium and phosphate of magne- sium, the sediment is usually composed of a combination of these two phosphates. Sediments wise produced the urine has rendered alkaline, or merely neutralized by Fig. a fixed alkali, such as potash or soda, for example, in consequence of the prolonged -Triple Phosphates (Feathery Form). 110 THE UKINE IN HEALTH AND DISEASE. use of alkalies as therapeutic agents. In this case the sediment usually consists of phosphate of lime. Phosphoglyceric Acid. — Phosphoric acid may be found in the urine in combination with glycerine, under the form of pliosplw glyceric acid. This acid is usually found in cases of leucocythaemia. According to Lepine and Egmonnet, it is found in normal urine to the extent of 15 milligrammes per litre, and its quantity is augmented after the use of chloroform as an anaesthetic. Qualitative Analysis of Phosphoric Acid. — The presence of phosphoric acid in the urine in combination with lime and magnesia is indicated by the precipitation of earthy phosphates by means of ammonia. In order to separate the phosphoric acid from the alkaline phosphates, filter the urine precipitated by the ammonia, and test the filtered liquid with magnesia mixture, or with a solution of uranium plus acetic acid, or with perchloride of iron, when a yellow precipitate of uranic phosphate and a white precipitate will be respectively produced. Quantitative Analysis of Phosphoric Acid. — Of the numerous processes recommended for this purpose, the most rapid is the volumetric method proposed by Neubauer. It is based on the following reactions : Acetate or nitrate of uranium gives with acetic solutions of phosphates a yellow flocculent precipitate of constant composition ; and when all the phosphoric acid is precipitated, the uranium salt added in excess gives with ferrocyanide of potassium a characteristic brown coloration. This process requires the following solutions : (1) A Standard Solution of Phosjrfioric Acid. — Dissolve in distilled water 3*087 grammes of dry acid phosphate of ammonia, and make up the solution to 1 litre. Fifty c.c. of this solution contain 0*1 gramme of phosphoric acid. (2) An Acetic Solution of Acetate of Soda. — In a little water dissolve 100 grammes of pure crystallized acetate of soda, add 50 c.c. of crystallized acetic acid, and a sufficiency of water to make up to 1 litre. (3) Solution of Ferrocyanide of Potassium. — A 10 per cent, solution. (4) A Standard Solution of Nitrateof Uranium. — Dissolve 20 NORMAL ELEMENTS OF THE UEINE. Ill grammes of pure and dry oxide of uranium in as little nitric acid as possible. Dilute to a litre and determine the titre as follows : Into a small beaker measure 50 c.c. of the phosphoric acid solution, then add 5 c.c. of the acetate of soda solution, and into the mixture, heated on a water-bath almost to ebullition, drop by means of a burette the solution of uranium until a pre- cipitate ceases to form. By means of a glass rod put one drop of the liquid on a fragment of porcelain, and with a pipette add a drop of the solution of ferrocyanide of potassium. If no color- ation is produced, add to the liquid ^ c.c. of the solution of uranium, and recommence the testing with the ferrocyanide and continue until a reddish-brown coloration is produced. This being obtained, measure again 50 c.c. of the phosphoric acid solution, and add 5 c.c. of acetate of soda solution, then add at once a volume of solution of uranium equal to that primarily employed, less | c.c. Heat to ebullition, add ^ c.c. of solution of uranium and test with ferrocyanide of potassium, continuing thus until the reddish-brown colour begins to manifest itself. Then read off from the burette the volume of the uranium solution employed to obtain the coloration. Supposing the volume to be 19*8, it is easy to determine to how much phosphoric acid 1 c.c. of the uranium solution corresponds. Since 50 c.c. of the phosphoric acid solution employed for the titration contain 0*1 gramme of this acid, 19*8 of uranium solution=0*l gramme of phosphoric acid, 1 C.C. = X, hence x=^-^ = 0*00505. Each c.c. of the uranium solution corresponds, therefore, to 0*00505 gramme phosphoric acid. To estimate the amount of phos- phoric acid in the urine, proceed in the same manner as for the standardization of the uranium solution. Measure 50 c.c. of the filtered urine, and add 5 c.c. of acetate of soda solution. Heat to ebullition, and add the uranium solution until a coloration is obtained with ferrocyanide of potassium. The number of c.c. employed multiplied by 0*00505 indicates the quantity of phos- phoric acid contained in 50 c.c. of urine, and this quantity multiplied by 20 gives the proportion per litre. 112 THE UEINE IN HEALTH AND DISEASE. Freund* proposes the following method for estimating the separate amount of monobasic and dibasic phosphates when the two exist together in the urine. The method is based on the property which monobasic phosphates possess of forming with chloride of barium an insoluble precipitate — acid phosphate of barium. With a liquid containing the two phosphates the amount of whose total phosphates is known, it suffices to add chloride of barium to obtain the monobasic phosphate precipitate. The phosphorus of the precipitate being estimated, subtract from the total to obtain the amount of the dibasic combination. Variations of Phosphoric Acid in Urine.— Phosphoric acid exists in the urine in combination with lime, magnesia and soda. It is the acid phosphate of soda which determines the acidity of the urine. An adult in good health using a mixed dietary eliminates on an average from 2 to 3 grammes of phosphoric acid in twenty -four hours. This quantity is augmented when animal food preponderates in the dietary, and also after the ingestion of phosphates or substances rich in phosphates. On the other hand, the phosphoric acid is diminished by fasting and by a vegetable dietary. The excretion of phosphoric acid is generally augmented simultaneously with that of urea and chlorides as the result of an abundant ingestion of fluids. Excessive intellectual or muscular exertion acts in a similar manner. Pathological Significance. — In acute febrile diseases, during the first few days there is generally a diminution of phosphoric acid in the urine, and towards the termination of their course, and when death is imminent, the diminution is still more pro- nounced. As the fever diminishes the excretion of phosphoric acid augments, and this continues during the whole of con valescence, especially when abundant nourishment is taken. In these cases, the amount may sometimes exceed the normal. In chronic diseases the elimination of phosphoric acid depends on the functional activity of the digestive organs. Generally speak- ing, the earthy phosphates diminish in cerebral affections, rheuma- * ' Ueber eine Method e zur Bestiminung von einfach -Saurem Phosphate neben Zweifach •Saurem Phosphate in Harn' (Centralb. /. Med. Wi88ehsch. 9 1892, No. 38, p. 689). NORMAL ELEMENTS OP THE URINE. 113 tism, mollities ossium, rickets, catarrh of the bladder, etc., while they are augmented in diseases of the spinal cord and kidneys, dropsy, atrophy of the liver, and glycosuria. In the last affec- tion the phosphaturia is frequently accompanied by azoturia. Tessier has described a condition to which he has given the name of ' diabetic phosphaturia,' or ' phosphaturia,' which is accompanied by disorders of the nervous system and pulmonary complications. He considers this state as symptomatic of tuber- culosis, or to indicate latent glycosuria. Bouchard has arrived at the following conclusions on this subject : (1) In the majority of cases of diabetic glycosuria, and especi- ally in cases of moderate gravity, with a small elimination of sugar and urea, phosphates are eliminated in a normal amount, or even to a less extent than normal. (2) The augmentation of the glycosuria may be accompanied by a parallel augmentation of phosphates. (3) When disassimilation is augmented in the diabetic, and the sugar is above the normal in quantity, this disassimilation takes place at the expense of the tissues which furnish the urea and the phosphoric acid, so that azoturia accompanies the phos- phaturia, and vice versa. (4) The parallelism between the elimination of the urea and that of the phosphates takes place only in the cases in which the elimination is above the normal. Anazoturia may be observed with a normal elimination of phosphates, an I hypophosphaturia with a normal excretion of urea. (5) It appears that phosphaturia is far from bein^ the rule in saccharine diabetes. When phosphates deposit in the urine, a short time after emission it assumes a milky appearance. At the moment of emission it is clear. Heat precipitates the phosphates, which are dissolved by a drop or two of acetic acid. Microscopic examination shows the characteristic forms of phosphates. Potash, Soda, Lime, Magnesia. These bases exist in the urine in tli3 form of chlorides, sul- phates, and phosphates. 8 114 THE UKINE IN HEALTH AND DISEASE. Potash and Soda. — A healthy man, on a mixed diet, elimi- nates in twenty-four hours 2 to 3 grammes of potash, and 4 to 6 grammes of soda. In febrile affections the excretion of potash is three or four times greater ; while that of the soda diminishes when the fever is at its height, but rapidly augments during its decline. After the ingestion of potash and soda salts, the urine presents a notable augmentation in fixed alkalies. Qualitative Analysis. — To 100 c.c. of urine add a little hydrochloric acid, and then two volumes of a clear mixture of. equal parts of alcohol and ether, with a little chloride of platinum. After a few hours there are deposited crystals of chloride of platinum and potassium, mixed with chloride of platinum and ammonia, whose octahedral form is characteristic. In the case of soda, evaporate the urine in a water-bath until crystallization takes place. A portion of the crystalline mass, introduced into gas-flame, imparts to it an intense yellow colour, whose spectrum exhibits a yellow ray coinciding with the line D of the solar spectrum. Quantitative Analysis. — The weight of the double chloride of platinum and potassium multiplied by 0*3051 gives the weight of the chloride of potassium ; the difference represents the weight of the chloride of sodium. To obtain the quantity of potash and soda multiply the weight of the chloride of potassium by 0*6317, and by 0*5302, the weight of the .chloride of sodium. Lime and Magnesia. — According to Neubauer, a healthy man excretes between 0*12 and 0*25 gramme of lime in twenty-four hours, and from 0*18 to 0*28 gramme of magnesia in the same time. Lime and magnesia exist in normal urine under the form of phosphates, and in pathological urine as sulphates, oxalates, and urates. The presence of lime and magnesia is thus demonstrated : Precipitate the urine by ammonia ; dissolve the precipitate, which is a mixture of basic phosphate of lime and of ammonio- phosphate of magnesia, in acetic acid ; then add a small portion of chloride of ammonium, and finally a solution of oxalate of ammonia, by which the lime is precipitated in the form of oxalate, while the magnesia remains in solution. To demon- NORMAL ELEMENTS OF THE URINE. 115 strate the latter, add ammonia to the filtered liquid, when a pre- cipitate of the triple phosphate results. Quantitative Analysis. — The weight of the triple phosphate precipitate multiplied by 0*3604 gramme gives the weight of magnesia. To ascertain the weight of lime, precipitate 100 c.c. of urine with ammonia. Eedissolve the precipitate in acetic acid, and add a sufficiency of amnionic oxalate to precipitate all the lime as oxalate. Allow the precipitate to settle, separate by nitration, ignite with the filter in a platinum crucible, when calcic oxide and carbonate result. Transfer to a flask by aid of a washing bottle, and add an excess of ^ nitric acid. Determine the amount of acid above what is required to saturate the lime by ^ caustic alkali, each c.c. of which is equal to 0*0028 gramme CaO. Ammonia. According to Neubauer, normal urine at the moment of emis- sion contains a small quantity of ammonia, in the form of carbonate, chloride, etc., amounting to 0*6 to 0*8 in twenty-four hours. This ammonia results from the food, the liquids ingested, and the inspired air. Qualitative and Quantitative Analysis. (See Abnormal Constituents of the Urine.) Variations in the Proportion of Ammonia in the Urine. — Ammonia is augmented in the urine by a dietary rich in animal food, and the ingestion of ammoniacal compounds, which pass, into the urine without undergoing alteration, such as the salts with mineral acids, or of vegetable acids which are transformed into carbonates. In disease the amount of ammonia in the urine is above the normal. In catarrh of the bladder the urine contains ammonia in the form of carbonate, arising from the • decomposition of urea in the bladder. 116 THE UKINE IN HEALTH AND DISEASE. Iron, Nitric Acid and Nitrates and Nitrites, Silica, Per- oxide of Hydrogen. Iron. — Iron is eliminated in healthy urine, according to Magnier, to the extent of 3 to 11 milligrammes per litre in twenty-four hours. Analysis. (See Medicaments and Accidental Elements of the Urine.) Nitrates and Nitrites. — The presence of nitrates, arising from certain principles of food, has been demonstrated by Schonbein in the urine. Potable waters, peas, salads, etc., contain small quantities of nitrates. Under the influence of putrefaction in urine undisturbed, the nitrates are transformed into nitrites. In order to demonstrate the presence of nitrates, evaporate a little urine to dryness with a little potash, and treat the residue with sulphuric acid. Nitrous vapours are evolved, which impart a blue colour to iodide — starch paper. If the urine be not fresh, and if the nitrates have been transformed into nitrites, the presence of the latter is demonstrated by adding to the urine a little solution of starch and iodide of potassium, and then a few drops of water acidulated with sulphuric acid, when a blue coloration results. Silica. To extract silica from urine, dissolve in a platinum crucible with an excess of carbonate of potassium and sodium the incinerated residue of from two to three litres of urine. Acidu- late with hydrochloric acid, and evaporate to dryness on a water bath. Treat the residue again with hydrochloric acid and water, when the silica is found to remain in the form of a white, taste- less, and odourless powder, soluble in a boiling solution of carbonate of soda. The quantity of silica voided with the urine in twenty-four hours varies from 0*02 to 0*03 gramme. Peroxide of Hydrogen has been shown by Schonbein to exist in normal urine. Its presence is demonstrated thus : Add to 200 c.c. of fresh urine a few drops of a solution of sulphate of indigo, so as to obtain a green coloration, and finally a small portion of a solution of the sulphate of protoxide of iron. If the NORMAL ELEMENTS OF THE URINE. 117 urine contains peroxide of hydrogen, the colour of the mixture changes from clear to brownish-yellow, in consequence of the discoloration of the indigo. Gases in the Urine. Carbonic Acid, Oxygen, Nitrogen. — The urine always con- tains in solution carbonic acid, oxygen and nitrogen. According to Morin, a litre of normal urine contains 15*957 c.c. of carbonic acid, 0*658 c.c. of oxygen, and 7*773 c.c. of nitrogen. All causes which accelerate respiration increase the amount of carbonic acid and nitrogen, and diminish that of oxygen. The com- bined portion of the carbonic acid is united to the alkalies and earthy salts in the form of bicarbonates. Its quantity is aug- mented in fevers pari passu with that of urea. Carbonic acid aids the solution in the urine of earthy phosphates. PART III. CHAPTER IV. ABNORMAL CONSTITUENTS OF THE URINE. ORGANIC SUBSTANCES — INORGANIC SUBSTANCES — ORGANIZED SUB- STANCES. Classification of Albumens — Properties of Albumen — Coagulation by Heat — Coagulation by Nitric Acid — Tests for Albumen — Fallacies in Heat Test — The Nitric Acid Test — Fallacies in Nitric Acid Test — Tanret's Reagent — Picric Acid Test — Feirocyanide of Potassium Test — Nitro-prussiate of Soda Test — Sodium Tungstate Test — Spiegler's Test — Stutz's Test — Roch's Test — Jaworowski's Test — Other Tests for Albumen— Mixed Albuminuria — Relative Value and Delicacy of Various Albumen Tests— Quantitative Analysis — Process of Tanret and Troyes — Bbdeker's Method — Process of Brandberg — Esbach's Process — Zahor's Method — Pathological Sig- nificance — Therapeutic Indications — Purulent Albuminous Urine — Globuline — Qualitative and Quantitative Analysis — Process of Hammarstein — Pathological Significance — Fibrine — Mucine— Pro- perties of Mucus — Analysis — Leucomaines and Ptomaines — Pep- tones — Properties of Peptoms -Analysis — Process of Hofmeister — Reaction with Tanret's Solution — Other Reactions— Pathological Significance — Hemi-albumose — Properties — Analysis — Transitory Albuminuria — Pathological Significance. The abnormal constituents of the urine may be considered as consisting of three groups, viz. : (1) Elements of an Organic Nature ; (2) Elements of a Mineral or Inorganic Nature ; and (8) Organized Substances. ABNORMAL CONSTITUENTS OF THE URINE. 119 ORGANIC SUBSTANCES. Albumen. Peptones. Glucose. Levulose. Lactose. Inosite. Cystine. Tyrosine. Leucine. Acetone. Melanine. Diverse acids. Bile elements. Fatty matter. Tube-casts. INORGANIC SUBSTANCES. Salts of ammonia (carbonate of ammonia, ammonio - phos- phate of magnesia, urate of ammonia). Sulphuretted hydrogen. ORGANIZED SUBSTANCES. Blood corpuscles (haemoglob- ine). Leucocytes (pus). Mucus. Epithelial cells. Spermatozoa. Infusoria. Organic Substances. Albumen. C 3 6H 56 N 9 0iiS (Lieberkhiin). Carbon ... ... ... ... 53 per cent. Hydrogen 7 Nitrogen ... ... ... ... 15*50 ,, Oxygen 23 Sulphur 1-50 „ 100-00 Albumen is primarily synthetically formed by plants. It is introduced into the animal organism as food, and there under- goes important and varied modifications before being in- corporated with, and forming part of, the living tissue. It exists in greatest abundance in blood-plasma. It likewise forms an important constituent of lymph and chyle, of serous fluids, and of the other textures of the body. It exists in large quantity in the egg, and this form of albumen is usually regarded as the standard of albuminous substances, other forms of albumen being classed in the degree of their constituent relationship to this variety. Other proteids exist in animal tissues,, which have 120 THE URINE IN HEALTH AND DISEASE. important relations to the pathology and diagnosis of disease. The entire group may be thus classified : Class I.-Native Albumen ... j \ ff^X^en. 1. Acid albumen or syntonin. Class II. — Derived Albumens { 2. Alkali albumen. 3. Casein. 1. Globulin (crystallin). 2. Paraglobulin (fibrinoplastin, serum globulin). Class III.-Globulins -^.Fibrinogen 4. Myosin. 5. Vitallin. Class IV. — Fibrin ( Mucin. Class V.— Coagulated Proteids ( Leucomaines, Ptomaines. Class VI.-Peptones \ P^apeptone-Hemialbu- mose or Propeptone Class VII. — Lardacein or Amyloid Substances.* According to Hoppe-Seyler, the composition of the foregoing varies from C 51*5, H 6'9, N 15'2, S 0*3, 0 209 to C 54*5, H 7'3, N 17*0, S 20, 0 23-5. Properties of Albumen. — Albumen exists in a soluble and in an insoluble form. In the former condition it exists in all the fluids and tissues of the body, and in vegetables. It is convertible into the latter form by boiling with water, by absolute alcohol, acids, and strong alkalies. On incineration it evolves nitrogen ; and heated in a tube with caustic potash, ammonia is given off, which may be recognised by its action on litmus paper, and the formation of white fumes on coming in contact with hydrochloric acid. Dried, it forms as an inodorous, insipid, and slightly yellow amorphous substance, soluble in water, but insoluble in alcohol. The presence of sulphur in albumen may be thus demonstrated. Boil albumen with a solution of caustic soda. A sulphide of soda is formed which gives a black precipitate with a salt of lead, or * For detailed relations of the foregoing the reader is referred to special works. ABNORMAL CONSTITUENTS OF THE UBINE. 121 by calcining a quantity of albumen with caustic potash and nitrate of potash in a porcelain crucible, a sulphate of potash is produced, easily recognised by the action of chloride of barium. From an aqueous solution albumen is precipitated by alcohol, which, according to the nature of the precipitate, may be redissolved in whole or in part. Albumen is coagulated by all the mineral acids with the exception of ortho- and pyrophosphoric acid. It is coagu- lated without combination by carbolic acid, picric acid, nitric acid, sulphuric acid, and tannic acid. Concentrated hydrochloric acid, especially with the addition of a little sulphuric acid, dissolves a small portion of the albumen, and imparts to the remainder an intense blue colour which persists a long time. Nitric acid causes serum-albumen to become yellow, and on the addition of ammonia a deep orange colour is the result. This is the xantJw- proteic reaction. A solution of mercurous and mercuric nitrates, made by dis- solving one part of mercury in two parts of nitric acid and four parts of water, imparts a deep-red colour to albumen in either the solid or liquid form when the mixture is warmed from 60° to 100° Cent. (Millon's reaction). As a test, this is not applicable to the urine, as four different precipitates are formed by it. Bichloride of mercury readily precipitates albumen from solution, the precipitate being soluble in an excess of albumen. It is likewise precipitated by nitrate of silver, acetate of lead, tannin, creosote, aniline, etc. It is not precipitated by formic acid, tartaric acid, nor acetic acid, the last of which separates proteine. Potash, soda, and the carbonates of these bases dissolve albumen, and prevent its coagulation by heat. Sulphuric ether coagulates egg albumen. The albumen of the serum is not so coagulated. Coagulation of Albumen by Heat.— If a solution of albumen, neutral or acid, be heated to a temperature of 62° Cent. (94° Fahr.), it begins to become cloudy owing to the separation of albumen ; at a temperature of 72° to 75° Cent. (104° to 107° Fahr.) the coagulation is complete. The more dilute the solution of albumen, the higher is the temperature required. The precipitate thus formed is insoluble in water or in a moderate quantity of nitric acid. The point of coagulation by heat is modified 122 THE URINE IN HEALTH AND DISEASE. by certain acid salts and some alkalies. Thus, sulphate of magnesia and sulphate of soda have jper se no effect upon albumen, but when the albuminous solution is saturated by them, the point of coagulation is lowered to 50° Cent. (82° Fahr.). It is important to keep this in view in testing for very minute quantities of albumen. Should the albuminous solution be alkaline, and especially if the quantity of albumen be small, coagulation on heating does not take place. It is, therefore, indispensable, under such circumstances, previously to acidulate the urine, or at least to render it neutral, and for this purpose it is necessary to employ an acid which does not coagulate albumen, such as acetic acid. "When the urine is alkaline, the acetic acid must be sparingly added, otherwise the albumen is not precipitated by heat. Sulphate of soda added to a solution of albumen, acidified by acetic acid, gives a precipitate of albumen on heating. Traces of albumen may thus be detected by satu- rating the urine with sulphate of soda, acidif3 T ing with acetic acid, filtering, and heating in a test-tube. It is important to note that urine containing semen, acidulated with acetic acid, gives a precipitate on being heated, the precipitate dissolving on the addition of an excess of the acid. Coagulation of Albumen by Nitric Acid. — Nitric acid coagulates albumen without combining with it. If it be added drop b}' drop to albuminous urine, a white cloud of albuminous substance is the result, which disappears on agitation. If in excess the precipitate is rcdissolved. If about a tenth or a fifth of the volume of urine be added of the acid, a copious and persistent white precipitate is the result. This precipitate par- takes sometimes of a colour derived from the oxidation — a pink colour — of uroerythrine, and sometimes, though rarely, of indigo. Tests for Albumen in the Urine. Coagulation of Albumen by Heat.— At a temperature of from 60° to 100° Cent, albumen contained in urine is coagulated. To ensure the greatest possible accuracy in testing for albumen by means of heat, the following precautions should be observed : The urine should be that passed after breakfast, as frequently ABNORMAL CONSTITUENTS OF THE UEINE. 123 the urine passed after resting and abstinence from food is free from albumen, while containing it after food and exercise. If the urine be acid, as it naturally is, it is not necessary to acidulate it ; but if it be alkaline, just sufficient acetic acid should be added to render it acid. In order to separate globulin, chloride of sodium or sulphate of magnesia should be added, and the urine filtered. A test-tube is then half filled with the clear urine, and the fluid is to be freely boiled. If albumen be present, and the circumstances of light, etc., favourable, the characteristic flaky albuminous precipitate is easily recognised. It is better to boil simply the upper stratum of the fluid, as in this manner the contrast between the two portions, especially against a dark background, reveals the smallest trace. This precipitate is unaffected by a small quantity of acetic or nitric acid, but is redissolved by an excess of them. Fallacies in the Heat Test. — A modification of albumen is met with occasionally which is not coagulated by heat.* Certain important precautions have to be observed in the treating of albuminous urine with acetic acid, in order to obtain a satisfac- tory precipitate by means of heat. If more acetic acid be added than is necessary to neutralize the free alkali and slightly acidu- late the fluid, boiling may produce a mere cloudiness. If more acid be then added, and the urine boiled, it becomes perfectly clear. If at first the acid be added in considerable quantity — for instance, to the extent of about a fourth— the fluid is unaffected by boiling, and then the addition of nitric acid does not cause precipitation of the albumen. Alkaline albuminous urine is not precipitated by heat, but the subsequent addition to it of nitric acid causes a precipitate of albumen. In alkaline urine the albumen exists as an albuminate of potash. Phosphates of lime or magnesia are thrown down by heat, and turbidity results from the escape of carbonic acid. This precipitate is distinguishable from albumen by being im- mediately dissolved by the addition of a few drops of acetic or nitric acid. Albuminous urine to which a drop or two of nitric acid may have been added accidentally, or purposely for the sake * Annal. des Malad. des Organ. Genit. Urin., 1888, p. 213, and Ibid., 1889, p. 703. 124 THE UKINE IN HEALTH AND DISEASE. of experiment, is not coagulated by heat. In this case the albumen had been converted into a nitrate of albumen. Urine containing pus is necessarily coagulated by heat. Urine containing mucin is not coagulated by heat, but the addition of acetic acid precipitates the mucin. Acetic acid also throws down cystin, and uric acid when in excess. The Nitric Acid Test. — In proceeding to test for albumen in urine by means of nitric acid, the urine should be rendered slightly acid by means of a few drops of acetic acid, and filtered. Cystin and mucin, if present, are thus separated. Two or three drachms of the filtered solution are then placed in a conical glass or test-tube. By means of a pipette, a small quantity of pure, colourless nitric acid is allowed to trickle down on the side of the glass, and thus mingle with the urine. The acid, having a higher specific gravity, passes under the urine, and at the junction of the two fluids a sharp white band or zone forms, varying in size with the quantity of albumen present. The acid may be first placed in the glass, and the urine subse- quently added, but the result is identical. The precipitate of albumen formed by the first few drops of acid is redissolved on shaking the fluid, but reappears and increases by further addition of acid, and does not disappear on being heated. Should the precipitate disappear on heating, it would be due to uric acid, urea, copaiba, etc. Not more than from a tenth to a fifth of nitric acid should be added to the urine. If the urine be rich in colouring matter, as in fever, at the line of junction of the fluids certain shades of colour may be formed, a red colour resulting from the presence of uroerythrine, a blue due to indigo, a rose-red to indican, a brownish-red to blood colouring matter, and a green to undecomposed biliary con- stituents. The albumen itself partakes to a greater or less degree of these colours, according to circumstances. Fallacies in the Application of the Nitric Acid Test. — With urine rich in urea, such as that of the dog, nitric acid gives a precipitate of nitrate of urea, which is much less soluble than urea, especially in acid solutions. The precipitate is distinguished from albumen by its crystalline form, by its solubility on the addition of a small quantity of water, by the fact that more or ABNORMAL CONSTITUENTS OF THE URINE. 125 less effervescence takes place when the nitric acid is added, arising from the partial decomposition of urea, that it is readily dissolved by heat, and, finally, that it forms higher up in the tube than the line of contact of the two liquids, and that the precipitate does not appear until after the lapse of a considerable interval. It first appears as a thin layer on the surface, and gradually thickens and extends from above downwards. Urates are decomposed by the addition of nitric acid, and a precipitate of uric acid is thus caused, which may be mistaken for albumen owing to its amorphous appearance. Slight heating causes the uric acid to disappear ; and on operating on a fresh specimen of urine, a precipitate is found to be occasioned by acids which do not coagulate albumen, such as phosphoric and acetic acid. If the urine contain a large quantity of carbonic acid, as arising from alkaline decomposition, and either in a free state or combined with ammonia, or potassium, or sodium, as from the administration of alkaline carbonates, or salts of the vegetable acids, such as citrates, tartrates, malates, etc., the addition of nitric acid causes its liberation with effervescence. "While under ordinary circumstances this does not interfere with the nitric acid test, it may so happen, as when, for instance, the quantity of carbonate of ammonia is very large, that the effervescence is such as completely to nullify the test. Again, in such a case, the amount of acetic acid necessary to neutralize and acidify is so large as permanently to hold the albumen in solution. Alka- line urines are always more or less opaque, owing to the presence of amorphous phosphates and bacteria, and cannot be sufficiently cleared by filtration. To obviate this difficulty, Hoffmann and Ultzmann recommend the following process : To the urine add about a fourth of its volume of liquor potassae ; warm the mix- ture and filter. Should the filtrate be not quite clear, a few drops of the following solution should be added: magnesium sulphate and ammonium chloride of each one part, distilled water eight parts, and pure liquor ammoniee one part. The fluid thus becomes clear, and the presence of albumen may be demon- strated by the use of acetic and nitric acid, or the ierrocyanide of potassium test. When the urine contains resinous substances. !6 THE URINE IN HEALTH AND DISEASE. such as copaiba or turpentine, the addition of nitric acid deter- mines a yellowish- white precipitate, which is dissolved by heating and excess of nitric acid. This substance is distinguished from albumen by its characteristic odour, by its solubility in alcohol, and by the fact that it is not precipitable by heat. If the urine be previously heated, the nitric acid does not precipitate the resin. Tanret's Reagent. — The double iodide of potassium and mercury, prepared as under, has been recommended by M. Tanret, of Paris, as a delicate test for albumen : Iodide of potassium ... ... ... ... 3*32 gr. Bichloride of mercury ... ... ... ... 1*35 gr. Acetic acid ... ... ... ... ... 20 c.c. Distilled water, q.s. ad ... ... ... 64 c.c. This test it employed in the ordinary manner, and is one of extreme sensibility. A weighty objection to it is that it precipi- tates alkaloids in the urine, and albumen, or some other albuminous substance, apart from any morbid process or mani- festation of ill-health. Thus, M. Chateaubourg, in 701 examina- tions of the urine of healthy persons, found ' albuminuria ' in no less than 592 instances, employing this test ; and Dr. Dickinson, in every one of 100 consecutive cases which presented them- selves in hospital and private practice, in many of which * there was no reason to doubt that the urine was absolutely natural.' Tanret's solution likewise causes a cloudiness in the urine when urates exist in excess. This disappears on heating, to reappear on cooling. If the urine be 'previously heated, Tanret's solution does not precipitate the urates. It precipitates peptones and globuline in the urine, and is a more delicate test for these than picric acid, but, unlike the precipitate with picric acid, that with mercuric iodide is not dissolved on the application of heat. Jaccoud* gives the following caution regarding Tanret's solution : ' I insist the more readily on the causes of error arising from the employment of Tanret's solution, seeing that it is so much used in France, and that I have been long struck with its drawbacks. It is too powerful or too delicate. It precipitates many other principles besides true albumen or serine, and I cannot help * Clinique Medical, 1886. ABNORMAL CONSTITUENTS OF THE URINE. 127 observing that it has been since its vulgarization (in France) that albuminuria in the apparently healthy has been so frequently discovered. Possessing the property of coagulating all proteic substances (not to speak of alkaloids), I am convinced that many of those cases presented, in reality, nothing in common with true albuminuria or serinuria. From this point of view, nitric acid and heat are the most certain reagents. Remove the globuline with sulphate of magnesia, filter, and treat the nitrate with heat and nitric acid or the acetic solution of ferrocyanide of potassium. If a precipitate result, it is certain to be one of serum albumen. The same fluid, treated by Tanret's solution, is as likely to give a precipitate of peptones as albumen.' The precipitate which Tanret's solution gives with albumen is not dissolved on heating. It is also insoluble in alcohol. It is thus distinguished from peptones and alkaloids. Picric Acid Test. — Picric acid was first suggested as an albumen test by M. Gallipe. A saturated solution of this acid added to urine is a delicate test for albumen. Such solution is slightly heavier than distilled water, so that, unlike nitric acid, it has a tendency to float on the surface of the urine. When the urine is alkaline, the addition of a drop or two of acetic acid renders the test more delicate. The precipitate so formed is insoluble by boiling. The coagulum formed with picric acid in cold urine requires a large excess of water for its solution. It is readily dissolved by caustic potash and ammonia, so that if the urine be alkaline, it should be acidified, or rendered neutral, before applying the test. The objections to the picric acid test are the following : It throws down creatinine, copaiba, peptones, mucin, quinine, cin- chonidine, morphia, atropia, and most other vegetable alkaloids ; but these precipitates, unlike that caused by albumen, disappear on the application of heat, and reappear as a cloud on cooling. On microscopic examination, as pointed out by Dr. George Johnson* the peptones present a homogeneous appearance, and are free from solid particles, while the precipitate of the vegetable alkaloids is finely granular. When peptones which have been dissolved by heat are precipitated on cooling, they contain, as Dr. Johnson remarks, exceedingly minute granules, which are 128 THE URINE IN HEALTH AND DISEASE. incessantly dancing about with so-called 1 Brownian movement.' The same authority states that ' there is no known substance occurring in either normal or abnormal urine, except albumen, which gives a precipitate with picric acid insoluble by the subse- quent application of heat. This is incorrect. Urine containing semen gives a precipitate with picric acid solution practically unaffected by heat. While the fluid is still warm the addition of a little nitric acid renders it quite transparent, and the transparency is permanent. If to the same urine before boiling nitric acid be added, after the precipitation by picric solution, the precipitate is dissolved, and the fluid becomes transparent, but the transparency soon passes off.' Uric acid is precipitated from normal urine by picric acid.* I have observed that the precipitate is very like albumen in appearance, and disappears on boiling, the fluid assuming a beautiful pink colour. This applies to urine containing potash in excess. In the case of urine containing an excess of urate of ammonia, the addition of picric acid, and exposure to air for a little time, causes the urine to assume a deep port- wine colour, but in my experience no precipitate. The deposit most readily and abundantly forms when the acid is employed in the form of fine powder, instead of the aqueous solution. Under the micro- scope the deposit appears as fine, needle-like processes, in the form of stars, and of more or less irregular prismatic crystals. Acted on by boiling water, part of the precipitate forms a com- bination of creatinine with pier ate of potassium. In using the aceto-picric test, or Tanret's solution and heat, according as the urine is rich in albumen, it appears in two forms. When but a small quantity of albumen is present, a mere cloud is produced, and this Professor Bouchard has proposed to term the non-retractile form of albumen. When present in larger quantity, distinct flakes are formed, termed by the same authority the retractile form. Dr. Dickinson considers the picric acid and the mercuric iodide tests as not sufficiently discriminating. Ferrocyanide of Potassium Test.— A solution of ferrocyanide of potassium acidulated with acetic acid forms a delicate test for * Zeit.fur Physiol. Chem., 1886, p. 39. ABNORMAL CONSTITUENTS OF THE URINE. 129 albumen. A preliminary objection to the use of all tests requiring acidulation by acetic, citric, or lactic acid is, that by either of these mucin is thrown down, and such acidulated tests are unsuitable for urines containing a small quantity of albumen. For ordinary purposes in practice, Dr. Pavy has suggested a most convenient contrivance for the application of this test ; pellets containing a sufficient quantity of citric acid and ferro- cyanide of potassium being formed and enclosed in an indiarubber capsule.* These are carried about in a small tube, and as no heat is required in testing with them, they are of easy appli- cation. Dr. Pavy's directions are as follows : About a drachm of urine is taken, an acid pellet is dropped into it, which a little agitation quickly dissolves. One of the ferrocyanide pellets is next dropped in, and the urine again shaken to facilitate solution. If albumen be present, a precipitate immediately occurs. Should the urine contain urates, it is to be clarified by heating. On the addition of the acid pellet alone a precipitate is sometimes formed, and this precipitate may be due either to mucin or to uric acid. In the latter case, dilution of the urine with an equal bulk of water prevents the appearance of the precipitate ; in the former case, the precipitate with both the acid and the ferrocyanide pellet should be compared with that resulting from the acii alone. A concentrated solution of ferrocyanide of potassium with acetic acid is, according to Hofmeister, the most delicate of all the albumen tests, and it precipitates all the albuminous bodies, but not peptones. Salkowski states that this test fails when a large amount of chloride of sodium is present, but the urine never contains this element in such quantity as to prevent the precipitation of albumen. Dr. Zouchlos recommends the following as convenient bedside tests for albumen in the urine : 1. Some drops of a mixture of 1 part of acetic acid and 6 parts of a 1 per cent, solution of subli- mate, when added to urine containing albumen, produce a slight cloudiness. Peptone, when mixed with acetic acid and sublimate in the above-mentioned proportions, causes no cloudiness, and * These pellets may be obtained from Mr. Cooper, 66, Oxford .Street, London. 9 130 THE UBINE IN HEALTH AND DISEASE. this is true also of uric acid, solution of urea, phosphates and sugar. When the urine is much concentrated, it does not be- come cloudy on the addition of sublimate and acetic acid. 2. Another method which is still more exact — even more so than that with the ferrocyanide of potassium and acetic acid — is the method with rhodanide of potassium and acetic acid in the cold. It is best to mix 100 c.c. of a 10 per cent, solution with 20 c.c. of acetic acid, and to add some drops of this mixture to the urine to be tested. When albumen is present in small quantities, a distinct cloudiness occurs immediately on the addition of the above-mentioned mixture ; when the amount of albumen is large, a thick white precipitate is thrown down. An excess of the fluid does no harm. Normal urine, when thus tested, invariably gives a negative result. The most convenient method is that with rhodanide of potassium and succinic acid, which can be carried about in the solid form in boxes. Equal parts of succinic acid and rhodanide of potassium are mixed together, and a small quantity is added to the urine. If even the smallest amount of albumen is present, cloudiness is produced. Nitroprussiate of Soda Test. — M. G. Nya* recommends a solution of nitroprussiate of soda as a test for albumen. It is to be employed in the same manner as ferrocyanide of potassium ; that is to say, before a solution of the reagent is added to the suspected urine, it must be previously acidulated by acetic acid. When precipitation of urates occurs, the urine must be clarified by heating. The nitroprussiate solution must be protected from light in order to prevent decomposition. Sodium Tungstate Test. — We are indebted to F. L. Sonnen- scheinf for the recommendation of sodium tungstate as an albumen test. J The solution of this salt must be acidulated with acetic or phosphoric acid. It precipitates peptones, acid urates, and mucin. In combination with strong acetic acid, sodium tungstate is a more delicate albumen test than with citric acid. With the latter it gives a marked mucin reaction. * Med. Chir. Rundschau, 1887, and Archiv de.r Pharm. xxv., 1887. t Journal of the Chemical Society, March, 1874. % Also as a delicate test for blood, producing, with ammonia, a green colour when blood is so diluted as not to be recognisable by the spectroscope. ABNORMAL CONSTITUENTS OF THE URINE. 131 Spiegler's Test.* — According to Spiegler, the following reaction discovers albumen when it exists in the urine in so small a pro- portion as 1 part in 250,000 : Corrosive sublimate 8 parts, tartaric acid 4 parts, distilled water 200 parts, glycerine 20 parts. A test-tube is filled to a third of its capacity with the reagent, to which a few drops of acetic acid have been added, by pouring along the tube wall, and the urine carefully added. When albumen exists, an opaque ring forms at the junction of the fluids. Should the urine at the same time contain iodine, the albuminous ring becomes of a yellow colour, the iodine yellow dissolving in alcohol. The added acetic acid separates almost all the mucin. With this reagent, Spiegler has been able to detect transitory albuminuria in from twelve to twenty-four hours after physical or intellectual exertion. Stutz's Test. — This consists of a mixture of bichloride of mercury, chloride of sodium, and citric acid. Added to albu- minous urine, this solution causes an abundant precipitate of albuminate of mercury. It is to be noted that it likewise precipitates uric acid in urines rich in this acid, and, therefore, in employing the test, the urine should be diluted with an equal quantity of water. Jaworowski (Wiadomosci Farmacentyezne, June, 1892) sug- gests, as a most delicate test for albumen, 1 part of molybdate of ammonia with 40 parts of water and 5 parts of tartaric acid. The presence of ^ooVoo °^ albumen is thus revealed. The urine must be limpid and acid. If necessary, it may be acidified with tartaric acid. The albumen may be completely removed by gradual addition of the reagent and filtration. An excess dissolves the albumen. Koch's Test— Sulphosalicylic Acid.— This acid, which is obtained by the action of sulphuric acid on salicylic acid, has been recommended as a most sensitive albumen test by M. Roch. When the acid is added to an albuminous solution, a white precipitate possessing an acid reaction results, which, on being treated with perchloride of iron, gives an intense red coloration characteristic of sulphosalicylic acid. The compound * ' Uber eine empfindliche Reaktion auf Eiweiss im Harn,' etc. (Centralblatt f. Klin. Medic, 1893, No. 3, p. 49). 132 THE URINE IN HEALTH AND DISEASE. thus formed with albumen is insoluble, and resembles that obtained with metaphosphoric acid. The whole of the albumen is precipitated, and 0*0005 gramme of albumen may be thus detected in 10 c.c. of albuminous urine. In employing the test a few crystals of sulphosalicylic acid are to be added to a small quantity of urine and the fluid shaken. The presence of albumen is revealed as above. The reaction is not interfered with by the presence of urea, uric acid, peptones, sugar or other substances. (ArcJiiv der Pharmacie, xxvii., 1889, 998; and L'Orose, xi., December, 1889, 413.) Other Tests for Albumen.— Of the other tests for albumen may be mentioned acidulated br ine, first suggested by Sir "William Koberts, and since abandoned by him ; alcohol, which, while it precipitates albumen, also coagulates mucus, and renders certain salts insoluble ; tannin, which also precipitates mucus, and other animal substances which the urine contains ; alum, which deter- mines precipitates in urine not albuminous ; corrosive sublimate, which seldom fails to precipitate urine whether it contains albumen or not, being decomposed by the sulphates, phosphates, and the organic matter in the urine ; carbolic acid, and Tidy's test, which consists of equal parts of carbolic and acetic acids, and acetate of uranium ; acetic acid, with sulphate or chloride of sodium (Panum, Heynsius) ; trichloracetic acid (Raabe) ; Millon's reagent ; biuret reaction ; reaction of Adamldevicz. Urine containing albumen, on being shaken, retains its froth for an indefinite period, sometimes for days. These tests are much less trustworthy than those described in detail, and do not merit further consideration.* Mixed Albuminuria. — Blood normally contains two coagu- lable albuminous substances, viz. : serum-albumen (serine) and globulin. In the majority of instances in which serum-albumen is found in the urine, globulin coexists with it. In a small number of instances, it sometimes happens that but one of these constituents is found, and thus we may have a pure case of serinuria or globinuria. Globulin is a more diffusible substance * Dr. Oliver, of Harrogate, has applied most of these tests to clinical purposes in the form of test-papers, after the manner first suggested by Professor de Luna, of Madrid {Lancet, October 14, 1882). ABNORMAL CONSTITUENTS OF THE URINE. 133 than serum -albumen, and when but one of these bodies exists, it is more likely to be globulin. When albumen reaches the stomach it is coagulated, and in this form insoluble in water. Here it is acted upon by the gastric juice, dissolved, and con- verted into peptone, though in this condition but slight traces of it are found in the blood ; yet, as with urea, uric acid, and kreatin, the kidney separates it from the blood, and it may exist in large quantity in the urine, constituting peptonuria. The conversion of albumen into peptone is by successive stages, and hence inter- mediate products may find their way into the blood, and ultimately into the urine. The most important of these compounds is hemi- albumose, or propeptone. According to Senator, the occurrence of propeptone in the urine is by no means a rare occurrence. Cases occasionally occur in which propeptone, serum-albumen, and globulin occur simultaneously in the urine, and to such the term * mixed albuminuria ' specially applies. Globulin is precipitated by sulphate of magnesia ; propeptone is not precipitated from its watery solution by boiling, but is precipitated in the cold state by acetic acid, and ferrocyanide of potassium, nitric acid, acetic acid, and a concentrated solution of chloride of sodium. Peptones are not precipitated by heat, nitric acid, nor the ferrocyanide test, but are precipitated by picric acid, the precipitate disappearing on the application of heat, to reappear on cooling, and by the mercuric-iodide and tungstate tests, the precipitant similarly disappearing and re- appearing. Fehling's solution, it may here be remarked, though in anticipation, gives a characteristic rose or pink-tinted colour with peptones. In all cases in which there is doubt as to the presence of pro- peptone, peptones, and albumen existing simultaneously in the urine, the following procedure should be adopted : (1) Acidify the urine with acetic acid, and then carefully add a concentrated solution of ferrocyanide of potassium. All the albuminous bodies are thus precipitated, but not peptones. (2) Add care- fully a little nitric acid to the non- warmed urine, and if cloudi- ness result, boil the urine. If the precipitate then partially or entirely disappear, the presence of propeptone is indicated. (3) A concentrated solution of chloride of sodium or sulphate of 134 THE URINE IN HEALTH AND DISEASE. magnesia added to urine acidulated with acetic acid or nitric acid gives a precipitate which disappears on heating; then prc- peptone is likewise indicated. Mucin is precipitated b} T citric or acetic acid, and may be removed by nitration. Hindenlang* recommends metaphosphoric acid as a delicate test for albumen, but it likewise precipitates peptones. A pre- cipitate caused by this acid, but not by acetic acid and ferro- cyanide solution, in the original urine, would indicate peptone to the exclusion of other substances. Should the urine give a precipitate with these two reagents, then by boiling and filtering the serum-albumen and globulin may be separated. The filtrate should not give a precipitate with acetic acid and ferrocyanide of potassium ; but if peptone be present, a precipitate would be given with metaphosphoric acid. Kelative Value and Delicacy of the Various Albumen Tests. — In view of the pathological importance which attaches to the early detection of albumen in the urine, and the vast number of details which fall to be, or are supposed to be, re- membered by the student, it is not desirable that equivocal albumen tests should be indefinitely multiplied, but rather, from the practical point of view, that the relative delicacy and conse- quent value of the best known of them should be determined. The following table exhibits the result of careful experiments undertaken by rue for this purpose. * Berlin Klinik Wochenschrift, 1881, No. 15. ABNORMAL CONSTITUENTS OF THE URINE. 135 Solution of sodium tungstate with citric acid. Well-markea instantaneous albumen preci- pitate. Distinct alDU- men reaction ; precipitate floating. Appreciable pre- cipitate. Not nearly so dis- tinct as in com- bination with acetic acid. AppreciaDie precipitate. No reliable precipitate. Solution of sodium tung- state with acetic acid. Copious and well- marked albumen precipitate. Well- marked albumen precipitate, clear super- natant disc. Distinct precipitate against clear super- natant disc. Distinct precipitate against supernatant fluid. No reliable precipitate. S 5 5; !3 e JrJf Distinct supernatant albumen precipitate, semi-trans- parent. Albumen precipitate ; more trans- parent, milky. No appre- ciable result. No result. 1 1 Coagulation by heat. Well-marked albumen pre- cipitate at boiling point. Distinct albu- men precipi- tate at boiling point ; less opaque. Distinct pre- cipitate at boiling point ; less copious. Appreciable precipitate at boiling point. Appreciable albumen reac- tion at boiling point. Albumen re- action at boiling point. Albumen re- action at boiling point. Faintest pos- sible reaction at boiling- point. Nitric acid, Heller s method. j Well-marked albumen pre- cipitate ; floc- culent and settling on repose. Well-marked albumen reac- tion ; more distinct on repose. Distinct pre- cipitate ; more mai'ked on repose. Distinct pre- cipitate, but only after an interval of 10 minutes. Distinct albu- men reaction after an in- terval of 15 minutes. Albumen re- action after 15 minutes. Faint albu- men reaction after 1 hour. No reliable result. Saturated solu- tion of -picric acid vnth citric acid. An abundant albumen preci- pitate of yellow- ish colour, occu- pying greater part of tube. Well-marked floating yellow- ish precipitate. Well-marked floating yellow- ish precipitate, less dense. Distinct super- natant yellow precipitate, t Very faint yellowish pre- cipitate. X Albumen reaction. § No appreciable reaction. 1 Saturated solu- tion of picric acid. A distinct opaque yellow- ish precipitate floating on the clear fluid underneath. Distinctly marked albu- men reaction ; yellowish supernatant precipitate. Yellowish supernatant albumen ; pre- cipitate more transparent. Marked yellow albumen reaction. Very faint yellowish preci- pitate. Albumen reac- tion slight. No appreciable reaction. 1 Tanret' 8 solu- tion with heat. A distinct precipitate, which settles and becomes flocculent on repose. Marked albu- men reaction ; precipitate flocculent and separating on repose. Marked albu- men reaction at boiling point. Distinct albu- men reaction at boiling point. Distinct albu- men reaction at boiling point. More distinct than 'Tanret' alone. Appreciable albumen reaction. Albamen reac- tion, but less marked than by No. 1. process. Negative result. Tanret's solu- tion, the urine poured drop by drov on it. A distinct opaque disc of albumen float- ing m a milky fluid. Distinct su- pernatant al- bumen preci- pitate, less opaque and more diffused. Distinct albu- men precipi- tate, less opaque and less copious. A delicate supernatant precipitate. Immediate but faint pre- cipitate. Supernatant pale albumi- nous disc. Faint super- natant albu- men reaction. Exceedingly faint albumen reaction. Fur- ther dilution negative. Quantity of albumen in 1,000 grms. & o o 3D iO © u bo iO 7* CN b & to p b h bo eo o b 0-015 gr. o p b 0-0035 gr. 136 THE URINE IN HEALTH AND DISEASE. The conclusions which these experiments impress upon me are : That the delicacy of the best albumen tests stands in the following order : Tanret's solution (open to the objections men- tioned above), heat, nitric acid, and aceto-picric solution. The foregoing table further shows (a result which is at variance with the statement of Hofmeister) that ferrocyanide of potas- sium with acetic acid proved in my hands the least delicate of the tests employed, ceasing to give any result with 1 part in 8,833 ; that tungstate of soda with citric acid is less delicate than with acetic acid, the latter ceasing to give a precipitate at 1 part in 33,333 ; that the aceto-picric solution ceases to give a reaction at 1 part in 148,857*5, but gives a reaction at 1 part in 66,666. Sir William Eoberts states that, in his hands, the picric acid tests gave a faint reaction in a watery solution con- taining 1 part in 100,000. I have been unable to confirm this.* Quantitative Analysis. — The most accurate, though certainly the most troublesome, method of determining the amount of albumen in solution in any fluid, is that by weighing. For this purpose coagulation is necessary, and this may be accomplished either by boiling the urine, or by coagulating the albumen by a chemical agent, filtering, collecting, and then weighing. If the former process be adopted, a certain quantity of urine is taken, * With reference to the heat test, Sir William Roberts ('Discussion on Albuminuria' at Glasgow Pathological and Clinical Society, 1884) remaiked : ' I gauged the delicacy of the test in the following manner : A moderately albuminous urine was diluted with 2,000 times its bulk of water. I could with certainty detect the presence of albumen in this dilution by the boiling test. Now, the urine operated on was found, on a careful weighing analysis, to contain 076 per cent of dry albumen. If you work out the sum which these figures furnish, you will get the astonishing result that the boiling test, with due acidula- tion, enables you to detect albumen in a watery solution which contains only one part in 250,000.' Sir William Roberts's calculation is slightly wrong. His data give one part in 263,158. Professor Grainger Stewart {Edin. Med. Jour., May, 1887) states it as his ( pinion that picric acid is the most delicate of all the reagents which we possess for albumen, the potassio- mercuric iodide ranking next to it ; whiie Dr. Unger Vetlesen, of Christiania, believes the relative delicacy to be represented by the following figures : Heller's test, 85 ; trichloracetic acid, 82 ; ferrocy. potass, and acid, acet., 82 ; metaphosphoiic acid, 72; picric acid in solution, 36 ; Glauber's salt and acetic acid, 25. ABNORMAL CONSTITUENTS OF THE URINE. 137 from 50 to 150 grammes being a convenient amount ; a few drops of acetic acid are added to it, so as to render it distinctly acid, and it is then filtered. According as the urine is rich in albumen, the nitration will be slowly accomplished. If rich in albumen, water should be added, so that from 25 to 100 cubic centimetres of the solution should contain from 0*30 gr. to 0*50 gr. of dried albumen, as judged by the qualitative analysis. The diluted urine is then put into a porcelain capsule, and gradually heated to ebullition, the fluid being stirred by means of a glass rod. The boiling should be continued from a quarter to half a minute, and the fluid then passed through a filter, whose weight has been previously determined. Filtration takes place rapidly ; the capsule is then washed with distilled water, the adherent particles of the precipitate being detached, and the fluid and the remaining precipitate is again thrown on the filter. Then, by means of a pipette containing boiling distilled water, the albuminous precipitate is washed, the jet being directed so as to convey the albumen towards the cone of the filter. The washing is to be continued until the albumen becomes perfectly white. The washing removes the chlorides from the albumen. Sometimes it is necessary to use hot alcohol for the purpose of washing. The filter and contents are now carefully placed in a stove, and exposed to a temperature of 100°C. Desic- cation takes from five to six hours, and the mass must be so arranged as to facilitate this. The desiccation is known to be complete when two weighings at an interval of from half an hour to an hour, in the stove, give an identical weight. From the whole weight that of the filter is to be subtracted, and the dif- ference represents the weight of the albumen. Two sources of error in this process are to be noted. In the first place, the albumen which passes into the urine is identical with that of the serum of the blood ; it contains serine and dis- solved fibrine. In the second place, the albumen retains always more or less of the colouring matter of the blood, and phosphates of lime and magnesia, especially if acetic acid has not been added. To obviate the former source of error, the albumen should be washed with alcohol, and to avoid the latter, the dried albumen should be incinerated, and the weight of the ash deducted. These 138 THE UEINE IN HEALTH AND DISEASE. sources of error are, however, so insignificant as to be clinically unimportant. Coagulation of Albumen by Carbolic Acid — Process of M^hu. — To the albuminous urine two or three drops of acetic acid are to be added, and the fluid filtered ; 100 c.c. of the filtrate are then taken, and 2 c.c. of ordinary nitric acid are added, with 10 c.c. of the following solution : Crystallized carbolic acid ... ... 10 grammes Commercial acetic acid ... ... ... 10 ,, Alcohol (90°C.) 20 The mixture being shaken, the albumen immediately coagulates, and the whole is thrown on a filter. Filtration takes place so rapidly that the uric acid is almost entirely found in the filtered fluid, where it gradually crystallizes. The albumen collected on the filter is washed with boiling water containing 1 per cent, of carbolic acid, and is then dried towards a temperature of 105° F. or C. ; any excess of carbolic acid, being volatile, disappears with the water. If the urine be rich in albumen, a preliminary experiment is made with from 25 to 30 c.c. It should be diluted with water, so that the volume will amount to 100 c.c. This process is not affected by the presence of sugar or such mineral substances as chloride of sodium, nitrate of potash, iodide of potassium, sulphate of magnesia, and ammoniacal carbonates. When the urine contains carbonate of ammonia, the precipitate has a creamy appearance. Process of Tanret and Troyes.— Tanret and Troyes have recommended, for the volumetric estimation of albumen, its pre- cipitation by a double iodide of mercury and potassium. For the precipitating solution the formula is : Potass, iodide 3 22 grammes, hydrarg. bichlor. 1*35 gramme, aq. destillat. ad 100 c.c. For the confirmatory solution : Hydrarg. bichlor. 1 gramme, aq. destill. ad 100 c.c. One drop of the precipitating solution given by a pipette of the above size precipitates 0*005 gramme of albumen, so that so many drops as it takes to precipitate all the albumen, so many times 0*005 gramme of albumen must have been in the solution. To save trouble in calculation, the same quantity ABNOKMAL CONSTITUENTS OF THE URINE. 139 of urine should always be taken, and the most convenient quantity to take is 10 c.c, as then the number of drops of the solution that it takes to precipitate all the albumen in this quantity of urine represents so many half -grammes to the litre. * Take then 10 c.c. of urine, add 2 c.c. of acetic acid, and stir with a glass rod ; add the precipitating solution drop by drop, stirring carefully each time, until the precipitate is no longer redissolved in the albumen in excess, i.e., as yet unaffected by the reagent ; after adding each drop of the solution, put a drop of the Urine on a porcelain dish and watch if a yellowish-red colour appears on adding a minute drop of the confirmatory solution. As soon as it does, all the albumen is precipitated and the process is finished, and the amount of albumen per litre will be at once arrived at by taking the number of drops employed of the pre- cipitating solution, subtracting three as having been used in excess to make the yellow colour perfectly apparent, and then considering the rest as so many half-grammes. The chemical reactions and data on which the above depends are 4KI + HgCl 2 = HgI 2 ,2KI-f 2KC1. When the double iodide of mercury and potassium thus formed is added to albuminous urine sufficiently acidified, all the albumen is precipitated in combination with the mercury and iodide of the reagent in the proportion of the equi- valent of HgI,KI (-=^HgI 2 ,2KI) weighing 393, to one equivalent of albumen C 36 H 56 N 9 0iiS weighing 1004, while the potassium is taken up by the acid of the urine. As long as any albumen remains in solution, the double iodide of mercury and potassium will not form red iodide of mercury when bichloride of mercury is added to it, but it does so as soon as all the albumen is preci- pitated. The solution formulated above is such that every drop of 0*05 gramme contains 0*00196 gramme of HgI,KI, and there- fore, in accordance with the equivalents given, will precipitate •005 of albumen, f Bodeker's Method. — Identical in principle with the fore- * Supposing it takes 10 drops of the precipitating solution to precipitate the albumen in 10 c.c. of urine, then 0*005 x 10 =*05 gramme of albumen, and 10 drops — 10 half-grammes to the litre ; for 10 : 1,000 :: *05 : 5. t 393 : -00196 :: 1004 : 0*005. 140 THE URINE IN HEALTH AND DISEASE. going process is that recommended by Bodeker. It is based upon the fact that potassic ferrocyanide completely precipi- tates albumen from an acid solution in the proportion of 211 ferrocyanide to 1612 albumen. The standard solution of ferrocyanide is made by dissolving 1*309 gramme of the pure salt in a litre of distilled water. One cubic centimetre of the solution thus prepared precipitates 0*01 gramme of albu- men.* Analytical Process. — Take 50 c.c. of the clear filtered urine, and mix with 50 c.c. of commercial acetic acid, and put the fluid into a burette. Five filters are then put into a corresponding number of funnels, a few drops of acetic acid being added, and filled up with boiling water. In this manner filtration takes place more rapidly. Ten c.c. of the ferrocyanide solution are then measured into a beaker with 10 c.c. of the ordinary fluid from the burette. The fluid is then shaken and poured upon No. 1 filter. If the fluid which passes through is bright and clear and of a yellowish colour, then the ferrocyanide will be in excess, and a drop of the urine added to it will produce a cloudi- ness. Otherwise, if not enough of the ferrocyanide has been added, the filtrate will be turbid, and pass slowly through. Fre- quently, in this case, both the ferrocyanide and the urine will produce a turbidity when added. The addition of too much urine in testing the filtrate for excess of ferrocyanide must be avoided, so that the precipitate of hydro-ferrocyanide of albumen may not be dissolved in the excess of albumen. According to the result obtained from the first filter, a second trial is made, increasing the quantity of urine or ferrocyanide half, or so, as much again, and so on until it is found that the solution first shown to be in excess is reversed. The mean is now taken between this quantity and the previous one, and the final test applied. f Example. — Fifty c.c. of urine containing albumen were mixed with a like quantity of acetic acid and tested as follows : * 211 : 1 :: 1612 : 7'6, and 1 : 1309 :: 7 '6 : 0*0099. f Sutton's 'Volumetric Analysis.' ABNORMAL CONSTITUENTS OF THE URINE. 141 Urine. Ferrocyanide. Tn filtrate urine gave In filtrate ferrocy- anide gave precip. 0 precip. faint precip. 0 (1) 10 c.c. (2) 10 c.c. (3) 10 c.c. (4) 10 c.c. (5) 10 c.c. 15 c.c. 0 17*5 c.c. 0 18 c.c. 0 20 c.c. precip. 10 c.c. 0 Hence 10 c.c. of the diluted urine=5 c.c. of the original secre- tion, contained 0*18 gramme albumen, or 36 parts per 1,000. This process is obviously more complicated and tedious than that of Tanret and Troyes, and possesses no superior advantages to commend it. Process of Brandberg. — This process consists in an applica- tion of Heller's method, and is based on the time necessary for the appearance of the albuminous principle in certain dilutions. According to Brandberg, Heller's reaction appears as follows : (a) Immediately, in a solution of one part of albumen in 10,000 of water (0*01 per cent.). (b) In from quarter to half a minute, in a solution of 1 in 20,000 (0-005 per cent.). (c) In about one minute and a half, in a solution of 1 in 25,000 (0*004 per cent.). (d) In from two and a half to three minutes, in a solution of 1 in 30,000 (0-0033 per cent.). (e) In about four minutes, in a solution of 1 in 35,000 (0*0028 per cent.). Basing the following procedure on (d), the urine is diluted with nine times its volume of water (one-tenth of urine), and Heller's test is applied as follows : By means of a pipette a little nitric acid is placed in a conical glass, and similarly the diluted urine, taking care not to mix the two. If after the lapse of three minutes an albuminous ring does not appear at the point of junction of the two fluids, it may be concluded that the quantity of albumen does not exceed 0*003 per cent., and consequently in the pure urine not more than 0*03 per cent. If, on the contrary, the reaction is established within three minutes, the urine must be further diluted in the following manner : Five glasses are taken ; into each glass are placed 2 c.c. of the urinary solution : 142 THE URINE IN HEALTH AND DISEASE. four c.c. of water are added to the first, to the second 13, to the third 28, to the fourth 43, and to the fifth 58 c.c. of water. To each of these solutions nitric acid is added with the precautions necessary in Heller's method. If one of them gives a reaction in from two and a half to three minutes, it is concluded that in that one the proportion of albumen is 1 in 30,000 or 0*0033 per cent. Knowing the number of cubic centimetres of water added, the quantity of contained albumen may be calculated by the following formula : 2 x 0-1 x x = (a + 2) x 0-0033,* in which a represents the number of c.c. of added water. The following table exhibits the proportion of albumen per cent., the number of c.c. of water added being known, and Heller's reaction being obtained in three minutes. * Supposing, for example, 8 c.c. of water have been added, then : 2 x 0*1 x x = (8 + 2) x 0*0033. 2 x 0-1 x x = (10) x 0 0033. 2 x 01 x x = -0.33. 0-2* = -033, and x = '033 -f- -2 = 0*165. ABNORMAL CONSTITUENTS OF THE URINE. 143 0.0. of Diluted Urine. C.C. of Water. Albumen per Cent. 2+ 4 = 0*049 = 0-099 2+ 2+ 2+ 8 10 13 = 0-165 = 0-198 = 0-247 2+ 2+ 2+ 2+ 2+ 16 19 22 25 28 = 0-297 = 0-346 = 0-396 = 0-445 = 0-495 2+ 2+ 2+ 2+ 2+ 31 34 37 40 43 = 0-549 = 0-594 = 0-643 = 0-693 = 0-742 2+ 2+ 2+ 2+ 2+ 46 49 52 55 58 = 0-792 = 0-841 = 0-891 = 0-940 = 0-990 2+ 2-h 2+ 2+ 2+ 2+ 61 64 67 70 73 88 = 1-039 = 1-089 = 1-138 = 1-188 = 1-237 = 1-485 Hammerstein has made experiments with a view to testing the accuracy of the above, and he has shown that with a little experience the amount of variation, as tested by weighing, does not exceed 0'05 per cent. Esbach's Process. — This method is based on the fact that picric acid precipitates albumen at the ordinary temperature, and that the precipitate deposits in a uniform state and degree of density. The apparatus employed consists of a tube, in appearance like a large-sized test-tube, but of greater thickness,. 144 THE UKINE IN HEALTH AND DISEASE. — R and graduated so as to indicate the amount of deposits. The graduation of the instrument represents in grammes the quantity of albumen contained in a litre of the urine operated upon, the interspaces diminishing towards the open extremity of the tube, the weight exercised by the reagent being greater on the portion of the deposit nearest it. The Reagent.— Take 10 grammes of chemically pure picric acid, and 20 grammes of citric acid dried in the air. Dissolve in 800 or 900 grammes of water, and, after cooling, add sufficient water to obtain 1,000 c.c, or 1 litre. The albuminous urine must be acid. If not acid, a few drops of acetic acid must be added. The urine is poured into the albumenimeter up to the mark U, and then the reagent is added up to the part of the tube indicated by the letter E. The fluids are then mixed without violent agitation, so as to prevent the formation of air-bubbles. This being accomplished, the open extremity is covered by means of a little gutta-percha sheeting or cork, and the instrument allowed to remain undisturbed in a vertical position for a period of twenty-four hours. At the expiry of this time, the figure indicat- ing the height of the deposit is noted, and shows in grammes the amount of albumen contained in a litre. The instrument is not graduated bej-ond 7 per 1,000. Hence, when the quantity of albumen exceeds this amount, it is necessary to dilute the urine, the result being multiplied by the amount of dilution, double or triple, as the case may be. The method is not adapted for minute quantities of albu- men, as it does not indicate less than 0*1 per cent. This process is suitable, from its simplicity, for clinical purposes ; and its accuracy is such that Graaf has found that, between the results obtained with it and the polarimeter, the variation did not exceed from 0*1 to 0*2 per cent. — U J Fig. 33.— Esbach's Albumeni- meter. ABNORMAL CONSTITUENTS • OF THE URINE. 145 Zohar's Method. — Zahor*has devised the following quick and ready method, which gives results accurate to the first decimal place. It depends on the difference in the specific gravity or density brought about in the urine by the removal of the albumen. The process, which is a densimetric one, is as follows : A preliminary examination of the filtered urine is made, in order to determine approximately the amount of dilute acetic acid necessary to precipitate all the albumen when boiled. This is ascertained by placing a small quantity of urine in a test-tube with acetic acid and boiling. The coagulum is then removed by filtration. The filtrate should yield no precipitate with acetic acid and potassium ferrocyanide. A convenient quantity of the filtered urine is now placed in a flask fitted with a cork, acetic acid having been added, and the flask is then placed in boiling water for ten or fifteen minutes. This brings about the coagulation of the albumen, w T hereupon the fluid is carefully filtered into a flask fitted with a perforated cork, through which a funnel is passed. The density of the urine and of the filtrate is then determined by means of a urinometer, graduated to the fourth decimal place. The difference between the initial density and the final density is now multiplied by the factor 400, the product giving the number of grammes of albumen present in 100 c.c. of the urine. Pathological Significance. — In the condition of perfect health albumen does not exist in the urine. From this stand- point, then, when it does so exist, it may be viewed as invariably possessing a pathological significance. It does not, however, follow that the appearance of albumen in the urine is neces- sarily due to structural change in the renal tissues, for, on the one hand, albumen may exist in the urine without any appre- ciable renal change, and, on the other, there may be considerable kidney change without the accompaniment of albumen in the urine. Two inferences seem to be justly deducible from these facts : on the one hand, conditions apart from the kidney may occasion albuminuria ; and, on the other, it is only when special portions of the kidney are affected that albuminuria results. * Zeitschrift fur Physiolog. Cliem. (12, 484-489). 10 146 THE URINE IN HEALTH AND DISEASE. Between the blood and the secretory apparatus of the kidney, as in the case of all the other secretory organs of the body, there is what may be called, for want of a better term, a vital correlation, whereby the cells separate from the blood the peculiar and special constituents of the urine. Why or how the cells of the various secretory organs secrete only their own peculiar secre- tions, to the exclusion of others, we cannot explain. We have to regard it simply as an ultimate fact. This correlation, in the case of the kidne} 7 , may be deranged from two opposite direc- tions — viz., structural change of the kidney, unfitting it for its work as a depurating organ, or change in the blood supplied to the kidney, poisoning, so to speak, the renal tissues temporarily, or leading to permanent change. Further, given perfectly healthy blood and perfectly healthy renal structure, the blood must pass through the gland at a certain rate of circulation and a certain degree of vascular tension. Hence albuminuria may be either of a pathological or physiological nature primarily, and its varieties may be thus classified : Pathological. Physiological. Structural change Blood changes, of the kidnej\ Conditions affecting blood in the the circulation of kidney. Excess of albumen in blood. Poisoning by phos- phorus, arsenic, mer- cury, and lead ; pneumonia, typhus, jaundice, scarlet fever, anaemia, leu- kaemia, diphtheria, diabetes, hyperp} 7 - rexia ; excessive alkalinity of the blood. Impressions on the nerves supplying the kidney (splanch- nics) ; spinal in- jury ; intestinal irri- tation ; masturba- tion; cutaneous exci- tation (cold bathing, etc.) ; asphyxia ; cerebral exhaustion (over - study, etc.) ; menstrual disorders. Diseases of the heart, lungs, liver, etc. ; atony of the renal bloodvessel; increased or dim- inished blood- pressure; tumours pressing on veins, pregnancy, etc. Further consideration of these various states does not fall within the province of this work. Therapeutical Indications. — In albuminuria arising from acute inflammation of the kidney, as in inflammatory affections of all complex organic structures, the great principle of physio- logical rest and vicarious action must be kept in view. Con- sequently the skin and bowels must be so acted upon as to spare the kidney and relieve it of as much work as possible. Hot baths and diaphoretics are therefore indicated, and such purga- ABNOKMAL CONSTITUENTS OF THE UBINE. 147 tives as remove the watery portion of the blood to the greatest extent, as elaterium, scammony, etc. Salines should on no account be administered, as they are eliminated chiefly by the kidney, and it is difficult to comprehend on what foundation in sense or reason the indiscriminate use of bitartrate of potash is advocated in acute nephritis. The same applies to large draughts of diluents, which simply increase arterial tension, induce renal embarrassment, and increased elimination of albumen. Small doses of bichloride of mercury with iodide of potassium have proved of signal benefit in my hands. Purulent Albuminous Urine. — Urine containing pus neces- sarily contains albumen, so that when microscopic examination reveals leucocytes or blood-corpuscles, the presence of albumen is to be anticipated. Should the leucocytes be in such quantity as to obscure the detection of albumen by heat, the urine should be acidulated with a few drops of acetic acid, filtered, and the usual tests applied. If the quantity of albumen be very minute after the addition of the acetic acid, a saturated solution of sulphate of soda should be added. By this means albumen may be detected in the urine of men suffering from gonorrhoea, or of females suffering from acute or chronic inflammation of the genital organs. In the case of purulent albuminous urine the question will arise, To what extent is the albumen derived from the pus alone '? or is this superadded to from a renal source ? The solution of these questions often rests on practical experience alone. The albumen due to pus is in relatively small proportion. In the case of a large quantity of pus with a small quantity of albumen, say lper cent., or a small proportion of pus with a large quantity of albumen (5 per cent., e.g.), the proper conclusion will be at once apparent. Confirmation must be sought in the presence in the urine of tube-casts, or renal epithelium, and in the indications afforded by clinical symptoms. Globuline (Paraglobuline ; Fibrinoplastic Substance). — The albuminous matter which exists in the blood-corpuscles has been termed globuline by Berzelius. It has been termed caseine of serum by Panum, and paraglobuline by Kuhne. In the urine globuline is most frequently found associated with true 10—2 148 THE UEINE IN HEALTH AND DISEASE. albumen (serine), but it may exist in an isolated condition, con- stituting the condition known as glohinuria. This substance may be conveniently extracted from the crystalline lens of the ox. The other globuline contained in the blood plasma (nbrino- plastic substance) may be found occasionally in the urine, but the former is the globuline especially eliminated with the urine. Urine containing globuline presents certain characters in common with albuminous urine. It is coagulated by heat, the fluid, however, remaining milky, and the coagulum does not become dense except in the presence of a sufficient quantity of a neutral salt (chloride of sodium or sulphate of soda). Globuline is in- soluble in water and alcohol and saturated solutions of neutral salts ; it is soluble in acetic acid and in dilute solutions of alkaline carbonates and phosphates. In moderately concentrated solutions of neutral salts it deviates the plane of polarization to the right. In presence of mineral acids and metallic salts it gives the reactions of albumen. The point of coagulation of albumen is 72°C. ; that of globuline is about 80°C. Globuline is coagulated by alcohol, by nitric acid, by potassium ferrocyanide with acetic acid, and by Tanret's solution ; so that it must be borne in mind that in albuminous urine submitted to these tests the globuline, if it exist, is also precipitated by them. The differential features of globuline as compared with albumen are as follow : (1) Ammonia and acetic acid separately employed do not precipitate globuline, but used successively they cause a pre- cipitate of globuline. It is immaterial which is first added, providing the latter be added in sufficient quantity to neutralize the former. (2) A solution of globuline is precipitated by passing a current of carbonic acid gas through it. This precipitate is redissolved by passing a current of air through the solution in like manner for a sufficient length of time. A concentrated solution of globuline feebly acid or alkaline is precipitated by chloride of sodium. Of all albuminous substances, sulphate of magnesia, precipitates globuline alone. To determine for clinical purposes the presence of globuline in the urine, a saturated solution of sulphate of magnesia is employed. To the urine previously filtered an equal quantity ABNORMAL CONSTITUENTS OF THE URINE. 149 of the solution is added. The combined fluids are to be well shaken and allowed to rest for twenty-four hours, when, if globuline is present, it appears as a floating coagulum. In rare cases it subsides. When the urine is distinctly acid, the sulphate of magnesia solution may be added at once. When, on the other hand, it is but feebly acid or alkaline, five or six drops of acetic acid should be added for 100 c.c. The precipitate thus obtained is easily dissolved by common salt. M. Pohl* gives preference to sulphate of ammonia over sulphate of magnesia. In testing serous liquids he adds it directly, and to acid urines after neutralization with ammonia, and separation of the phosphates by filtration. To urine thus rendered alkaline the solution of sulphate of ammonia is to be added. After an hour's repose, the precipitate is collected on a filter, washed with sulphate of ammonia, dried at 100° C, and weighed. The whole is incinerated, and the weight of the ash subtracted. Quantitative Analysis. — In estimating the quantity of globuline in any given specimen of urine, the albumen must be previously removed, and vice-versa. To determine primarily if urine contain globuline, a certain quantity of filtered urine should be diluted with fifteen or twenty times its bulk of water, and a few drops of acetic acid added, when, if globuline is present, a turbidity, or even a precipitate, results. Process of Hammar stein.— Filter 50 c.c. (or 100 if it contain no albumen). The reaction ought to be acid. Mix with an equal quantity of a saturated solution of sulphate of magnesia, and lay aside for twenty-four hours, when flakes of globuline will have separated. The precipitate is carefully collected, the filter paper washed, first with a saturated solution of sulphate of magnesia, and then with boiling alcohol acidulated with acetic acid, and finally with boiling distilled water, which does not dissolve the globuline by reason of the addition of the alcohol and the acetic acid. Dry and weigh. The globuline may be preferentially estimated by difference. Thus — the albumen and globuline may be estimated en masse by coagulation. Then the * Archiv. fur Kxper. Pathol, und Rundschau fur die Pharmacia, xiii., p. 369, 1887. 150 THE URINE IN HEALTH AND DISEASE. globuline may be separated by sulphate of magnesia, and the fluid containing only albumen filtered. A few drops of acetic acid are then added and the albumen coagulated. From the combined weight of the albumen and globuline that of the albumen alone is subtracted, and the result is the weight of the globuline. The amount of dilution by the sulphate of magnesia solution must be taken into account. Pathological Significance. — Globuline is almost invariably accompanied by albumen in the urine, and is usually much less abundant. In acute nephritis it becomes augmented* coin- cidently with the diminution of albumen, and considerable globinuria is of grave import, and a diminution of its elimina- tion of favourable augury. Fibrine. — When the urine contains blood, it necessarily contains fibrine. It may exist independently after acute in- flammatory affections of the genito-urinary tract and kidneys, and appears under the form of a gelatinous coagulum, or a flaky mass either at the moment of emission of the urine or shortly afterwards. It sometimes exists in such abundance as to form with the urine a gelatinous mass, so that the vessel containing it can with difficulty be emptied. This form of coagulable urine is more frequently met with in warm climates, where chyluria is associated with fibrinuria. Hoffmann and Ultzmann have noticed a transitory fibrinuria in certain cases of villous tumours of the bladder, the urine being of a reddish or pale yellow colour. In cases of poisoning by cantharides, especially, fibrine is apt to exist in the urine. In order to isolate this fibrine, the urine is filtered and the deposit remaining on the filter washed with water. This is in- soluble in alkalies and diluted acids. Mucine. — Murine exists in the secretions of all the mucous surfaces of the body. Normally, it exists to a small extent in the urine— 0*5 to 1*0 gramme per litre according to Meisner. Its proportion is increased when the mucous membrane of the urinary tract is irritated, as in catarrhal affections and febrile affections in general. The mucus normally found in the urine is probably secreted by itself by the glands at the Level of the * Estelle, Faveretj and Hoffmann. ABNORMAL CONSTITUENTS OF THE URINE. 151 trigonum vesicce ; when the secretion is abnormally abundant, it is probably derived from the ureters and secretory structure of the kidney. Mucus existing to an abnormal extent in the urine of females is often derived from the vagina. Mucus does not exist in the urine in a soluble form, and may therefore be separated from it by nitration. Properties of Mucus. — Mucus is an albuminous substance of a white, flaky appearance. It absorbs, and becomes swollen by the absorption of, water. Dried by heat, it forms a gelatinous mass, on which water has little effect. It is in reality insoluble in water, in which, however, when the quantity is larger, it is capable of being so diffused as to pass through a filter as if a solution. Mucine is precipitated by acetic acid, and the precipi- tate is unaffected by excess of the acid. Mucine is likewise precipitated by alcohol, in which it is insoluble. It is insoluble in ether, in organic acids, and in dilute mineral acids, while it is dissolved by the concentrated. Alkalies readily dissolve mucine, notably acetate of potash. Sulphate of magnesia, bichloride of mercury, neutral acetate and sub-acetate of lead also precipitate it. It is not coagulated by heat, and on heating, acid nitrate of mercury gives with it a bright rose colour. Analysis. — Microscopic examination does not reveal the presence of mucus, as it is so transparent as not to modify transmitted light. If acetic acid be previously added, micro- scopic examination reveals mucus as a delicate membrane which is coloured by tincture of iodine. Sometimes mucus appears in the form of filaments, which may be mistaken for tube-casts, and may appear opaque from a deposit on them of urate of soda. They are distinguished from casts by their size, their secondary ramifications, and their association with epithelial scales and mucous corpuscles. Acetic acid renders these filaments more apparent. Urine containing an excess of urates is precipitated by acetic acid, the precipitate being insoluble in an excess of acid, but on being heated the precipitate disappears. This dis- tinguishes the precipitate from mucus. When the urine is also albuminous, a few drops of acetic acid should be added, and then three or four times its volume of con- centrated alcohol. After standing for some time the fluid is 152 THE URINE IN HEALTH AND DISEASE. filtered to separate the albumen precipitated b}^ the alcohol, and the nitrate is mixed with an excess of acetic acid. Leucomaines and Ptomaines.— According to Pouchet and Gautier, the urine always contains in the state of health a small proportion of leucomaines, or physiological alkaloids. These are considerably increased in infectious diseases, such as typhus fever, and certain nervous affections. Eobin states that in typhus fever the urine also contains ptomaines, or cadaveric alkaloids, originating in perversion of disintegration or bacterian fermentation. PEPTONES. Peptones are the result of the complete action of the gastric juice on albuminous substances. By hem/i-albumose oy propeptone is understood one of the products of this transformation. These compounds may be artificially produced by means of pepsine and pancreatine, and both are found in the urine under certain con- ditions, either separately or in combination with albumen. Properties of Peptones.— Peptones are white, amorphous, and slightly bitter. They dissolve with facility in water, are crvstallizable, and sparingly soluble in alcohol. They are in- soluble in ether and chloroform. They are not precipitated by heat, like albumen and globuline, nor by ferrocyanide of potas- sium and acetic acid, like globuline, albumen and hemi- albumose ; they are precipitated by tannin, a weak solution of hydrochloric acid, phosphotungstic acid, phosphomolybdic acid, metaphosphoric acid, picric acid, bichloride of mercury, nitrate of mercury, iodide of mercury and potassium (Tanret's solution)) nitrate of silver, and acetate of lead in ammoniacaJ solution. On heating with nitric acid, like albumen, they give the coloured xanthoproteic reaction, and with caustic soda and sulphate of copper solution the characteristic red biuret reaction. "With Millon's solution a red colour is produced, as in the case of albumen, but of much greater intensity. Analysis. — The biuret reaction affords the best evidence of the presence; of peptones in the urine. Should the urine contain albumen, it should be acidulated with acetic acid, and boiled ABNORMAL CONSTITUENTS OF THE UBINE. 153 with a saturated solution of chloride of sodium. The albumen is separated by nitration and the biuret test applied to the nitrate. Process of Hofmeister. — To the urine 2 percent, of acetate of soda is added and perchloride of iron guttatim until the red colour is permanent. Neutralize the urine by an alkaline solution, and boil until all the iron is precipitated in the form of a basic acetate, carrying with it the albumen. The filtrate should be entirely free from albumen, and unaffected by the ferrocyanide of potassium test. The special peptone tests can then be applied. Otherwise, filter about half a litre of urine, after agitation with a little neutral acetate of lead in order to eliminate and decolorize mucine if present. To a portion of the filtered fluid add from 5 to 10 per cent, of concentrated hydrochloric acid and phosphotungstate of soda, thus : Phosphotungstate of soda ... ... 25 grammes. Hydrochloric acid 5 ,, Distilled water... 250 ,, Add so long as a precipitate is formed ; filter and wash the pre- cipitate with water containing 4 or 5 per cent, of concentrated sulphuric acid until the filtrate is colourless. Add an excess of solid hydrate of baryta, heat gently with a little water until the fluid, at first of a greenish colour, becomes yellow, filter and apply the biuret test.* Reaction with Tanret's Solution. — Tanret's solution gives a precipitate with peptones which disappears on the application of heat and reappears on cooling. If the hot test-tube be im- mersed in cold water the precipitate appears at the cooled part. Reaction with Millon's Solution. — Millon's solution gives a cherry -red colour with peptones. Reaction with Tannin, etc. — Tannin, bichloride of mercury and chlorinated water give an abundant white precipitate with peptones. Picric Acid Reaction. — Picric acid solution gives a precipi- tate with peptones which disappears on heating, Albumen may be thus separated from peptones by filtering the boiled fluid ; the * So called because the bicyanate of ammonia gives the same coloration when applied to the same principles. 154 THE URINE IN HEALTH AND DISEASE. peptones pass through, and leave the coagulated albumen on the filter. If the urine contain alkaloids, such as quinine, picric acid gives a similar precipitate, which dissolves on heating. If the urine contain mucine, as shown by its becoming cloudy on the addition of acetic acid, it should be separated by neutral acetate of lead. Pathological Significance.— Peptones are found in the urine in cases of fibrinous pneumonia, acute rheumatism, phthisis, tubercular meningitis, puerperal scepticaemia, and deep-seated abscesses of bone, and elsewhere, especially when a process of absorption has been established (pyogenic peptonuria of Von Jaksch) ; in pernicious anaemia,* progressive paralysis, and scor- butus (haematogenetic peptonuria of Von Jaksch) ; in carcinoma of the stomach and in typhoid fever (enterogenetic peptonuria of Maixner). Peptonuria is evidently caused by a destruction of leucocytes, or the regression of plastic exudation. Hemi-albumose (Propeptone). — Hemi-albumose, as its name implies, is a compound intermediate between albumen and peptone. It was first described by Bence-Jones as occurring in the urine in the case of osteo - malacia. Subsequently Kiihne and Salkowsky confirmed this observation. Leube found it in the urine in a case of urticaria, Neale in a case of haemoglobinuria, and Von Jaksch in a case of tuberculosis with nephritis and peritonitis. Properties. — Hemi-albumose gives most of the albumen re- actions, but it dissolves with difficulty in cold solutions, though rapidly on boiling, by which it is contradistinguished from albumen. Analysis. — If an excess of acetic acid be added to urine con- taining hemi-albumose (and neither albumen nor globuline), and fjuttatim a solution of ferrocyanide of potassium, a precipitate results, which disappears on heating. Urine rich in salts ought to be previously diluted. By saturating such urine with sea- salt, a precipitate of hemi-albumose is caused, which is increased by the addition of acetic acid, and entirely disappears on heating, reappearing on cooling. Should the urine simultaneously contain hemi-albumose, * Neurol Ctntralblatt (No. 5, 1894). ABNORMAL CONSTITUENTS OF THE URINE. 155 albumen, and globuline, the presence of hemi-albumose is determined as follows : Saturate the urine completely with a solution of marine-salt, add an excess of acetic acid, boil and filter. The albumen and globuline remain on the filter, and the hemi-albumose passes through, and separates on cooling. The acetic acid and ferrocyanide of potassium test may also be applied to the filtrate. Transitory Albuminuria.— The subject of transitory, or cyclical, albuminuria has of recent years received considerable professional attention, and various conflicting deductions have been drawn from the occurrence. The merit of having first directed attention to albuminuria independently of structural renal change is usually ascribed to Gubler, in 1865 ; but as long ago as 1852 Dr. Warburton Begbie, of Edinburgh, in a paper read before the Medico- Chirurgical Society of that city, drew attention to the subject, defining temporary albuminuria as 1 the manifestation and continuance of albumen in the urine during a limited period, and unconnected with any serious organic change in the kidney.' The literature of the subject has been largely added to since then by many well-known observers. The percentage in which albuminuria occurs in obviously healthy persons has been variously stated by authorities, one author (De La Celle) estimating it as high as 84 per cent. ; but in this case Tanret's test seems to have been relied upon for the detection of albumen, and its fallaciousness as an albumen test has already been referred to. Dr. Grainger Stewart (Brit. Med. Jour., 1887) believes that albuminuria exists in 30 per cent, of the community. In seeking for an explanation of albuminuria, the normal function of the kidney has to be kept in view. The function of the Malpighian body is that of filtration ; that of the cells of the convoluted tubes excretion — the separation of the urinary constituents from the blood. Accordingly, Bernard observed that the veins in the glomeruli contained less dark blood than the veins in general, the arterial blood not having yet parted with its vital constituents. Filtration being the function of the glomeruli, it is obvious that this function will be influenced by 156 THE URINE IN HEALTH AND DISEASE. the principles and conditions affecting osmosis ; hence an excess of water in the blood, and the presence of alkalies, will stimulate the act of nitration. According to Heidenhain, it is the external layer of the epithelium of the Malpighian capsule that offers resistance to the passage of albumen. If this layer be supplied with impure blood, or affected by certain poisonous substances introduced into the blood, it undergoes a change (fatty degeneration, for instance), and permits of the transuda- tion of albumen. The vaso-motor nerves keep the bloodvessels in a state of moderate contraction. If their ganglia are stimulated or irritated, their inhibitory power is impaired, and dilatation of the vessels ensues. Under these circumstances albuminuria (vide 1 Anatomy and Physiology of the Kidney ') is apt to occur. If the cutaneous capillaries are contracted, increased pressure takes place in the Malpighian bodies, and diuresis and albuminuria may result. Albuminuria, in the sense that albumen in the urine is not compatible with perfect health, must always be considered as of pathological significance, though not necessarily indicating structural renal change. From these and the foregoing observa- tions and facts the following conclusions may be drawn : (1) That the presence of albumen in the urine of apparently healthy persons is of frequent occurrence. (2) That position exercises an influence on the secretion of albumen, the horizontal position causing its diminution or total disappearance in the urine, it being apt to occur on rising, and especially after breakfast — a fact capable of three different explanations ; (a) The sudden dilatation of asthenic bloodvessels and interrupted circulation ; (b) the effects of digestion and gastro- intestinal irritation, and possibly an undue supply of albumen ; and (c) that the alkaline tide is highest during the morning hours (effect on osmosis). (3) That certain diseases (vide p. 146) so alter the com- position of the blood and its contained albumen that the vital relationship between it and the Malpighian capsule is changed, and albumen consequently transudes (dyscrasic albuminuria). In this case the albumen, according to Bouchard, forms a ABNORMAL CONSTITUENTS OF THE URINE. 157 uniformly cloudy mass, and is said to be non-retractile, in contradistinction to the flaky form of albumen (retractile), due to renal lesion, and coming directly from the blood. As a rule, the albumen in the urine arising from structural renal change is not precipitated by organic acids ; in cyclical albuminuria, on the other hand, the proteid matter is, as a rule, precipitated by organic acids. (4) Bodily exertion notably augments the proportion of albumen in cases of transitory albuminuria. (5) Cold bathing causes an increase of the albumen in the urine in transitory albuminuria by increasing the vascular renal pressure. (6) Nervous hyperexcitation of various kinds causes temporary albuminuria, such as protracted intellectual work (often in students), excessive irritation and exhaustion of the genital centres in the lumbar region, acting reflexly on the splanchnics, as from masturbation, excessive sexual indulgence, and men- struation and its disorders. Simple, mental emotion may produce a similar result, as in the case mentioned by Basham of a man subject to attacks of hematuria, Mayer's case of hema- turia as a sequel to a fit of passion, and the cases cited by Flirbringer of emotional albuminuria. (7) Transitory albuminuria is more frequent among children than in adults. (8) Albuminous urine is usually above the specific gravity of 1014. The quantity of albumen ehminated in various diseases ranges from 1 gramme to 20 or 30 in twenty-four hours. The albumen is said to be in small amount when it does not exceed 2 grammes, moderate from 6 to 8, and considerable when exceeding from 10 to 12 grammes. Pathological Significance. — As to prognosis, the absence of tube-casts and a high specific gravity justify a favourable prog- nosis. It is the retention of urinary products, and not the loss of albumen to the blood, that causes death in albuminuria. Cases have been known in which albuminuria existed for over thirty years. In all such cases the specific gravity of the urine continues high. 158 THE UKINE IN HEALTH AND DISEASE. GLUCOSE (DIABETIC SUGAR). History — Chemistry of Sugars — Tests for Sugar in the Urine — Trom- mer's Reaction — Fallacies of Trommer's Test — Fehling's Reaction — Fallacies of Fehling's Test — Purdy's Method of Estimating Sugar in the Urine — Schmiedeberg's Solution — Crismer's Test — Bismuth Re- action of Bbttiger — Hoppe-Seyler's Reaction — Almen's Reaction — Indigo Reaction — Phenyl-Hydrazine Reaction — Agnosti's Reaction — Picric Acid Reaction — Fermentation Test — Specific Gravity of Diabetic Urine — Quantitative Analysis — Urine containing less than 5 per cent. Sugar. — Duhomme's Quantitative Analysis — Ap- proximate Estimate of Sugar by Specific Gravity — Gerrard's Per- centage Glycosometer — Optical Quantitative Analysis — Pathological Significance — Idiopathic Glycosuria — Therapeutic Indications — Simulated Glycosuria. C 6 H 12 0 6 . Carbon ... ... ... ... 40'00 Hydrogen ... ... ... 6*66 Oxygen ... ... ... ... 58*34 100*00 According to the writings of Celsus, Aretaeus and Galen, the disease termed \ diabetes ' (cia, ' through,' j3alvo, 1 1 go ') seems to have been recognised in a general way by the ancients. The progressive emaciation characteristic of the malady was observed as being accompanied by inordinate thirst, voracious appetite, and excessive discharge of urine. It was not, however, until 1674 that the urine in certain cases was discovered to possess a sweet taste, and the honour of this discovery, on which followed the es- tablishing of the distinction between diabetes insipidus and glyco- suric diabetes, is due to Willis, an English physician. A hundred years subsequently, Dobson, of Liverpool, discovered that the blood as well as the urine contained sugar ; and he inferred therefrom that this sugar was separated from the blood, and not formed by the kidney. In 1778 Cowley separated the sugar from the urine in a free state. In 1815 Chevreul pointed out that the sugar existing in the urine in cases of diabetes mellitus was different from cane sugar and closely resembled that of the grape ; and in 1825 Tiedmann and Gmelin ascertained that during its passage along the alimentary canal starchy matter was transformed into sugar. ABNORMAL CONSTITUENTS OF THE URINE. 159 Normally, sugar is found in the small intestine, and in the chyle after the ingestion of saccharine or starchy matter, and in the blood. The hepatic vein (Claude Bernard) abounds in it, while it does not exist in the portal, a fact demonstrating the sugar- forming function of the liver. This sugar is formed from an intermediate albuminoid product called glycogen, belonging to the amyloid group. This is a white substance which iodine colours violet-blue, and nitric acid transforms into xyloidine, an explosive material like gun-cotton. Sugar is not burned off in the liver, but disappears in the capillary system, after under- going a series of changes, ultimately represented by water and carbonic acid. Temporary glycosuria may be occasioned, accord- ing to Frerichs, by (a) poisoning by carbonic oxide, curara, nitrate of amyl, and large doses of morphia, chloral, prussic acid, sulphuric acid and alcohol ; (b) by digestive derangements, catarrh of the stomach, cirrhosis of the liver, thrombosis of the portal vein ; (c) by derangements of the nervous system, neuralgia, sciatica, lesions of the spinal cord, cerebral excite- ment, disseminated sclerosis, apoplexy, etc. According to Worrh- Muller cane-sugar, grape-sugar and milk-sugar, taken in doses of from 50 to 250 grammes, pass directly into the urine, causing temporary glycosuria. Levulose, taken even in large doses, is never found as such in the urine. Milk-sugar sometimes appears in the urine after child-birth, and especially when the secretion of milk by the mammae is embarrassed. Hofmeister and Kaltenbach have also found it in the urine of infants exclusively fed upon milk. Bernard has caused the appearance of sugar in the urine by pricking the floor of the fourth ventricle. It is sometimes alleged that sugar exists normally in urine in very small quantity, but this has not been satisfactorily demonstrated. Chemistry. — Sugars are divided into the following groups : (Glucoses) C 6 H 12 0 6 (Saccharoses) C^H^On ( Glucose, or Dextrose, or Grape -Sugar. ( Levulose. { Cane-Sugar or Sucrose, Maltose. Lactose or Milk-Sugar. (Amyloses orAmyloids) C 6 H 10 O 5 160 THE URINE IN HEALTH AND DISEASE. Fig. 34. — Tabular Crystals of Grape-Sugar. Glucose (sugar of diabetes), in its perfectly pure state, is of white appearance. It most frequently presents a yellowish colour. Its crystalline character is quite different from that of cane-sugar. It crystallizes in four or six sided rhomboidal prisms, while grape-sugar occurs in small cubes or square plates. It is less sweet than cane sugar, and less soluble in water, but more soluble in alcohol. It is insoluble in ether. Sucrose and glucose possess right - handed rotation, and deviate the ray of polarized light from left to right according to the amount of sugar present, a fact by which its O amount in diabetic urine may be estimated. Glucose combines readily with caustic alkalies, forming gluco- sates. Thus it combines with lime, baryta and potash. If an alcoholic solution of potash and glucose be mixed, glucosate of potash immediately precipitates in white flakes. If the mixture be subjected to heat, it becomes of a yellow or dark-brown colour, owing to the formation of glucic and melassic acid, according to the quantity of glucose and potash present (Moore-Heller's Keaction). If to a soluble glucose an excess of potash or soda be added, and a solution of sulphate of copper, the result is a bluish alkaline liquor, which, on being heated, gives a yellowish-red precipitate of protoxide of copper (Cu 2 0) (reaction of Trommer, Fehling and Worm-Muller). Glucose is acted on by mineral acids, by which it is trans- formed into black or brownish products. Nitric acid oxidizes it, forming oxalic (H 2 C 2 0 4 , 2H 2 0) and saccharic acid (H 2 C 6 H 8 0 8 ). Acted upon by hydrochloric or sulphuric acid, cane-sugar is converted into grape-sugar. This is easily demonstrated in the following manner : Dissolve a few grains of cane-sugar in water in a test-tube. Add a few drops of a solution of sulphate of copper and a considerable quantity of a solution of potash, and heat the ABNOBMAL CONSTITUENTS OF THE URINE. 161 mixture to the boiling-point. No change occurs. To another portion of the sugar solution add a drop of sulphuric acid, and boil for ten or twenty minutes. Add the solution of sulphate of copper and potash as above, boil, and a yellowish-red precipitate of cuprous oxide (Cu a O) immediately falls. Here the acid has converted the cane-sugar (C ia H M O u ) into ' invert sugar ' (a mixture of dextrose and levulose), so-called because it rotates a ray of polarized light to the left, whereas cane-sugar is dextro- rotatory. C^H^On-f-HoO == C 0 H 12 O 6 -f C 6 H 12 0 6 Both cane-sugar, maltose and grape-sugar yield alcohol and carbonic acid by fermentation. The cane-sugar probably always passes into grape-sugar before the production of alcohol begins. C 6 H 12 0 6 = 2C 2 H 5 OH + 2C0 2 (Grape-sugar) (Alcohol) (Carbonic Acid) Extraction of Glucose from Diabetic Urine. — Evaporate the urine on a water-bath until it is of a syrupy consistence ; leave it to settle in a cold place, when, at the expiry of a few days, a crystalline deposit will have formed. By treating these crystals with absolute alcohol, urea and extractive matter are separated. They are then dissolved in boiling alcohol and the solution evaporated. TESTS FOR SUGAR IN THE URINE. Moore's Reaction. — Equal quantities of non - albuminous urine and a solution of caustic potash are to be mixed in a test- tube. The earthy phosphates are first precipitated, and may be separated by filtration. The fluid is then boiled, when, if it contain sugar, it assumes a colour passing from pale yellow to dark brown. The colour is due to the successive formation of glucic and melassic acids, and disappears on the addition of a few drops of nitric acid, the characteristic odour of caramel being evolved. For the purpose of comparison, it is better to confine the action of heat to the upper portion of the tube. Unless the urine contain a considerable quantity of sugar (3 per cent., or 1^ grains to the ounce), the test is not sufficiently discriminating. 11 162 THE URINE IN HEALTH AND DISEASE. Bouchardat prefers lime to the potash solution, as the latter colours many of the extractive matters of the urine. Fallacies of Moore's Test. —Urine containing the pigments of rhubarb and senna becomes reddish-brown on the addition of alkalies when cold. Urine containing pyrocatechin becomes brown on exposure to air, especially after the addition of an alkali. Trommer's Eeaction. — This test is based on the property which grape - sugar possesses of reducing oxide of copper in alkaline solutions by the aid of heat. To about 5 c.c. of filtered urine free from albumen (it is not necessary to remove the albumen if it does not exceed 0*2 per cent.), add from 1 to 2 c.c. of a 10 per cent, solution of potash or soda. A 10 per cent, solution of sulphate of copper is added drop by drop until the bluish precipitate of hydroxide of copper ceases to dissolve. If the urine contain sugar, a considerable quantity of the oxide of copper is dissolved, and the liquor assumes an azure blue appearance. Heat is applied to the boiling-point, when, towards the upper portion of the tube, a yellowish -red precipitate of protoxide of copper appears. The heat is then withdrawn, and the reaction continues to extend throughout the liquid. This reaction is sufficiently marked when the proportion of sugar is not under 0*2 to 0*3 per cent. Fallacies of Trommer's Test. — Trommer's test is not reliable when the quantity of grape-sugar is small. Uric acid, creatinine, and certain extractive matters, reduce the copper solution when the sugar is absent, and especially if the urine be concentrated. The reduction by these substances, generally speaking, takes place only at the boiling-point. Exception, however, is to be noted in the case of uric acid, a precipitate of oxide of copper often forming at 90° or 100° Fah. In consequence of this source of fallacy, too strong heat should not be employed, nor should its action be long continued. In some cases, secondary reduction of the copper takes place. This does not indicate the presence of sugar, as the action in this case is immediate. Trommer's test has thus to be performed with care. In doubtful cases, only a few drops of the solution of copper (1 to 3) should be added. If, on the application of heat, reduction is manifested ABNOKMAL CONSTITUENTS OF THE URINE. 163 by decoloration, more solution has to be added, until a decided reaction is produced. Fehling's Reaction. — This test is also based on the reduction of an alkaline solution of copper by glucose. The solution is prepared as follows : 34*65 grammes of pure dry crystals of ordinary sulphate of copper are dissolved in about 250 c.c. of distilled water ; 173 grammes of pure crystals of double tartrate of potash and soda (sel de Seignette) are dissolved in 480 c.c. of a solution of caustic soda of sp. gr. 1*14. The solutions are mixed, and water added to 1 litre. A clear, deep blue solution is thus obtained, Fehling's solution, of which 100 c.c. represent 3*464 grammes of sulphate of copper, and correspond to 0*5 of a gramme of pure anhydrous grape-sugar, 0*475 of cane-sugar, 0*82 of maltose, and 0*45 of starch. Place 5 or 6 c.c. of Fehling's solution in a test-tube, and boil. If there is no precipitate, which shows that the reagent is pure, the suspected urine is added by pouring it carefully along the tube, so as to be superimposed on the test solution. If sugar be present, on boiling a greenish layer first appears, rapidly passing, through yellow, to orange or red, the precipitate extending to the entire fluid. If the sugar be in small quantity, the fluid must be boiled for a few minutes. This method is preferable to adding tjie reagent to the boiling urine. Modification of Fehling's Solution, by Ost* — The solution recommended by M. Ost contains per litre, crystallized sulphate of copper 23*5 grammes, dry carbonate of potash 250 grammes, bicarbonate of potash 100 grammes. This solution offers the following advantages over Fehling's solution : It can be kept without undergoing change, and it less profoundly decomposes the sugars during determination. 50 c.c. of this solution corre- spond to 100 milligrammes of inverted sugar, 102*5 milligrammes of dextrose, 90 milligrammes of levulose, and 117 milligrammes of galactose. Fallacies of Fehling's Test. — If Fehling's solution be too long kept, it spontaneously undergoes a process of reduction. This is said to be due to the formation of racemic or paratartaric acid, into which exposure converts the tartaric acid. If no precipitate * Zeitschrift fur Anal. Chemie, xxxix. (1891). 164 THE UEINE IN HEALTH AND DISEASE. occur with Fehling's solution on boiling, its delicacy is unimpaired ; but if so, a little more potash or soda should be added, and the liquid filtered, when it is again available. It is sometimes recommended to keep the copper and the alkaline solutions separately, and mix only when required for use ; but this is quite unnecessary if the foregoing precautions be observed. The addition of glycerine to Fehling's solution has been recom- mended for longer preservation, but it must be remembered that the glycerine of commerce is almost invariably impure. In employing Fehling's solution, any albumen contained in the urine must be separated by coagulation by heat, or precipita- tion by subacetate of lead. If the urine contain albumen, the reduction is prevented, and the fluid becomes of a violet colour. The presence of ammoniacal salts also interferes with the reduction, a part of the soda of the ' Fehling ' being used up by the salts. Should the urine have undergone ammoniacal fermentation, it should be boiled with a solution of caustic soda so long as ammonia is given off. It may subsequently be tested for sugar. Uric acid and urates also cause a reduction of the copper, especially after protracted boiling and during the process of cooling. This source of error may be evaded by treating the urine with subacetate of lead, which removes albumen and urates. Any quantity of sugar exceeding 3 id 4 per 1000 is readily detected by Fehling's solution ordinarily employed. It sometimes happens that glucose in diabetic urine is replaced by dextrine. In this event, according to Bouchardat, the copper reduction takes place only after prolonged boiling. The urine of individuals taking turpentine, copaiba, chloroform, chloral, camphor and cubebs, reduces the copper solution. Pyro- catechin, benzoate of soda, and glycerine, also reduce 'Fehling.' The precipitate of the phosphates caused by the mixing of the two fluids sometimes persists in a state of fine division, and may be mistaken for copper reduction. The colour of the precipitate is, however, different, and after a few minutes' repose the phos- phates settle in the bottom of the tube, while the copper sub- oxide remains suspended for many hours. Purdy's Method of Estimation of Sugar in the Urine.— Instead of Fehling's solution, this author employs the following : ABNORMAL CONSTITUENTS OF THE URINE. 165 Pure sulphate of copper ... ... ... 4*15 grm. Pure mannite ... ... ... ... ... 10 Caustic potash ... ... ... ... ... 20*40 ,, Aramonia (D = 0*880) 30 „ Glycerine ... ... ... ... ... 50 c.c. Distilled water q.s. to ... ... ... ... 1000 The sulphate of copper is first dissolved in water, and the glycerine and mannite are then added ; the potash is separately dissolved in water, and after cooling the two solutions are mixed. The ammonia is added, the solution is carefully filtered, and distilled water is added to make the solution up to a litre. 25 c.c. of this solution are reduced by 15 milligrammes of glucose ; the deep blue coloration disappears, and the result is a perfectly clear, colourless liquid. The copper solution should be heated in a capsule to the boiling-point, and the urine added drop by drop at intervals of from two to three seconds. The results are very accurate. If the sugar is in great quantity, the urine should be diluted with water {Pliarm. Zeitsch.fur Buss., xix., 1890). Schmiedeberg's Solution.* — In Schmiedeberg's formula, mannite replaces the potassio-tartrate of soda. The solution is prepared as follows : Dissolve 34*632 parts of crystallized sulphate of copper in 200 c.c. of water, and 15 grammes of pure mannite in 100 c.c. of water. These two solutions are combined, and 480 c.c. of a solution of caustic soda, sp. gr. 1*145, added, and sufficient water to make 1000 c.c. According to Schmiedeberg, this solution keeps better than Fehling's. Crismer's Test.— M. Crismer has recently advocated the use of safranin as a test for sugar. If 1 c.c. of saccharine urine be heated to ebullition with 5 c.c. of a solution of safranin and 2 c.c. of caustic potash solution, discoloration of the safranin at once takes place. On cooling, the solution becomes turbid. This reaction has the advantage over Fehling's solution in not being decolorized by uric acid, creatinine, chloral, chloroform, peroxide of hydrogen, nor the hydroxylamine salts. Albumen decolorizes it but slowly. Bismuth Reaction of Bottiger. — If a solution of glucose with a concentrated solution of caustic soda or carbonate and * Journal de Pharmacie de 1' Alsace- Lorraine, January, 1886. 166 THE URINE IN HEALTH AND DISEASE. a little nitrate of bismuth be heated together to the boiling- point, metallic bismuth* is obtained as a fine black powder. This reaction demonstrates the presence of 0*1 per cent, of sugar. Nitrate of bismuth is neither reduced by uric acid nor creatinine, but it is reduced on prolonged heating by other indeterminate substances. In albuminous urines a sulphide of bismuth may be produced by this test. Albumen should, therefore, be previously separated. Hoppe-Seyler's Reaction, f — The following reagent is recom- mended by Hoppe-Seyler. The reaction is based on the forma- tion of O-nitrophenyl- propionic acid from indigo, when the latter is boiled with an alkali and a reducing substance. The process is as follows : Take 5 c.c. of a half per cent, solution of O-nitrophenyl-propionic acid in soda and water, and boil during thirty seconds with ten drops of the urine to be examined. If the mixture becomes of a deep blue, it contains a reducing substance equal to at least 0*5 per cent, of sugar. Normal urine thus treated becomes of a green colour. The presence of albumen in urine does not prevent this reaction, and the minutest quantity of sugar is thus detected. Almen's Reaction. — This reagent is made according to the following formula : 10 grammes of nitrate of bismuth, 40 grammes of crystallized nitrate of potash and soda, 62 grammes of caustic potash and distilled water to 500 c.c. About 5 c.c. of the urine are mixed with from 0*5 to 1 c.c. of Almen's liquor, and heated to boiling for one or two minutes. If the urine contain a moderate amount of sugar, it becomes of a dark colour, which deepens with the continuance of heat until it becomes brownish black. This test demonstrates the existence of from 0*1 to 0*05 per cent, of sugar. J After the ingestion of turpentine and rhubarb, it gives with the urine a similar black colour, in the latter case due doubtless to its action on chryso- phanic acid. Indigo Reaction. — In order to apply this test, any albumen * Probably mixed with Bismuth oxide. + 1 Ueber eine Reaktion ziim Nachweis von Zucker im Urin, Auf Indigobildung,' Zeitschrift f. Physiolocj. Chemie, 1892, t. xvii., p. 83. t Annal. de la Society Med. Chir. de Litye, et Repertoire de Pharmacie, March, 1889. ABNORMAL CONSTITUENTS OF THE URINE. 167 which the urine may contain must be removed by precipita- tion and filtering. It must then be rendered alkaline by a solution of bicarbonate of soda. A solution of indigo is then added to the extent of causing a well-marked blue colour. On being heated, the liquor, if it contains sugar, becomes almost completely decolorized, passing through violet, purple-red, red, yellow to pale yellow, and on exposure to the air it resumes its original colour, passing inversely through the foregoing shades of colour (Mulder's reaction). Phenyl-Hydrazine Eeaction. — This test is as follows: A small portion of hydrochlorate of phenyl-hydrazine with twice the quantity of sodium acetate is placed in a test-tube half filled with water, and warmed. After adding an equal volume of the solution to be tested, the mixture is boiled for twenty minutes, when, on cooling (sugar being present), yellow crystalline needles of a compound of glucose and phenyl-hydrazine (phenyl-gluco- sazine) are deposited. These crystals have a definite melting- point of 204° to 205° C. This is a very delicate test, and is applicable to the detection of very small quantities of sugar. In normal urine, in the hands of Von Jaksch, a negative result was always obtained with this reagent. Agnosti's Reaction. — To detect glucose in aqueous solutions Agnosti recommends the following : Five drops of chloride of gold (1 per 1,000) and two drops of a 5 per cent, solution of caustic potash are added to the suspected fluid. It is then boiled, when, on cooling, if it contain glucose, it assumes a violet colour if the solution be aqueous, and a port-wine colour if of urine. The other elements of the urine do not give this reaction. If albumen be present, it should be previously removed. Picric Acid Reaction. — A solution of potash and a few drops of picric acid solution added to saccharine urine cause a deep-red coloration, due to the formation of picraminic acid. Fermentation Test. — To apply this test two flasks are taken (Fig. 35) : Into the flask A from 20 to 30 centimetres of urine are introduced, with a little yeast and a pinch of tartaric acid. The neck of the flask is closed with a cork pierced by two tubes, the tube a passing to the bottom of the flask, and a second tube (c) connecting with B, and passing to an equal depth. The flask B 168 THE URINE IN HEALTH AND DISEASE. is half filled with a solution of lime or baryta, and the orifice (6) of the tube a is sealed with a piece of wax. The apparatus is placed in an atmosphere with a temperature of 15° to 20° C. (59° to 77° Fahr.). Within twelve hours fermentation will take place, as evinced by the evolution of carbonic acid gas from the flask A, and the formation of a precipitate of carbonate of lime or baryta in the flask B. To be certain that the carbonic acid does not proceed from the decomposition of the yeast alone, the experiment should be repeated, employing pure water instead of the fluid supposed to contain sugar. Theoretically, 48*89 parts of carbonic acid correspond to 100 of glucose ; but according to Pasteur, not only are alcohol and carbonic acid formed in the process of alcoholic fermentation, but likewise a little glycerine and succinic acid. Hence in practice it is found that 48*88 cor- respond to 100 parts of glucose. Sir William Koberts has shown that after fermentation ' the number of degrees of " density lost " indicated as many grains of sugar per fluid ounce.' Specific Gravity of Diabetic Urine.— While a high specific gravity does not absolutely demonstrate the presence of sugar in urine, when it exceeds 1036, in pale urine, the chances are largely in favour of the presence of sugar. Fig. 35. — Fermentation Apparatus. ABNOBMAL CONSTITUENTS OF THE URINE. 169 Quantitative Analysis. — The amount of sugar contained in any solution may be determined chemically or optically. In the former method, which is absolutely accurate, Fehling's solution is conveniently employed as a standard reagent. One c.c. of this solution is reduced by 0*005 of glucose (10 c.c. are con- sequently equal to 0*05). Into a porcelain capsule pour 10 c.c. of Fehling's solution, which dilute with 40 c.c. of water. Into a burette, graduated to tenths of a c.c, put, for example, 10 c.c, of urine, diluted with, say, five times its volume of water. The Fehling's solution is now completely boiled over a spirit-lamp ; and the diluted urine from the burette carefully mixed with it, until the decoloration is complete, and a red precipitate of oxide of copper, or a yellow one of the hydrated oxide, appears. On referring to the burette, suppose you find, for example, that 9 c.c. of the diluted urine have been used to effect this change, then 1*5 c.c. of pure urine reduces 10 c.c. of Fehling's solution ; and as 10 c.c. of Fehling correspond to 0'05 grammes of glucose, 1*5 c.c. of this urine must contain 0*05 grammes of glucose, = 33-33 gms. per litre (1-5 : 1000 : : 0'05 : 33*33). In order to obtain exact results in this experiment, the urine must be previously filtered, any albumen separated, and it ought to be so diluted as to contain not more than 5 per cent, of sugar, It is important to note when the blue colour has completely dis- appeared, and complete reduction of the copper has taken place. To determine this, the fluid is to be rapidly filtered, and one portion of it boiled with Fehling's solution, and another with diluted urine. No precipitate should result in either case. If in the first instance a precipitate forms, it is obvious that too much urine has been added, and in the second, not sufficient. The experiment should be repeated, and the mean of successive trials taken in order to obtain conclusive results. Or if to about 1 c.c. of the filtered fluid a few drops of a solution of ferrocyanide of potassium be added, and a brown colour results, it is shown that non-reduced copper still exists. Urine containing less than 5 per Cent, of Sugar.— While, on the one hand, if the urine be rich in glucose, it is better to dilute the solution so as to contain about 10 grammes per litre, on the other, if the proportion is below 5 per cent., the influence 170 THE URINE IN HEALTH AND DISEASE. of other substances, which interfere with the copper reduction, is more appreciable; hence it is necessary to purify the urine by treating it with basic acetate of lead in the following manner : To 10 c.c. of urine in a graduated burette, add a tenth of its volume of subacetate of lead ; shake well, and filter. To remove the lead, a weak solution of carbonate of soda should be added to make the volume equal to 50 c.c. ; mix well, filter, and apply the Fehling test. • Table indicating the Amount of Sugar per Litre in Urine estimated by Fehling's Solution. Quantity of Fehling's C.C. of Urine Amount Quantity of Fehling's C.C. of Urine Amount of necessary to of Glucose per necessary to Glucose per Solution. decolorize. Litre. Solution. decolorize. Litre. Gr. Gr. ro 50 12*5 4'00 1-5 33-33 13-0 3-84 2-0 25 ]4-0 3-75 2-5 20 15 0 3 33 3-0 16-66 16-0 3-12 c 3.5 14-275 C 170 2-94 .2 ".3 4-0 1250 .2 18-0 277 4'5 11-11 19-0 2 63 "o m 5-0 10 Ul 20-0 2-50 w 5-5 9-09 QQ 21*0 2-38 & 6-0 8-33 ~b0 .5 22-0 2 27 6-5 7*69 23*0 2-17 PR CM 7-0 7-11 24-0 2-08 7-5 6-66 25-0 2-00 o 8-0 6*25 o 30-0 1665 6 8-5 5-88 6 35-0 1-428 b o 9-0 5-55 6 40-0 1-25 i—i 9-5 5-25 o i— ( 45 0 111 10-0 5 50-0 1-00 30*5 4-76 60-0 0-83 11-0 4-54 70-0 071 11-5 4-34 80-0 063 12 4-15 90-0 100-0 055 0--50 Duhomme's Quantitative Analysis.— In this process the chemical principles are the same as in that by Fehling's solution, ABNORMAL CONSTITUENTS OF THE URINE. 171 but the apparatus and subsequent calculations are different, and both are exceedingly simple. This method is, therefore, admir- ably adapted for clinical purposes. The apparatus required consist of some ordinary test-tubes, and two of Limousin's pipettes graduated to 1 and 2 c.c. respectively. Like all other fluids of the economy, the urine varies in composition and specific gravity from time to time. With these varying conditions, the number of drops contained in a given amount of urine — say, 1 c.c. — will correspondingly vary. A pipette is filled to the extent of 2 c.c. with Fehling's solution, which are transferred to a test-tube, and diluted with an equal quantity of liquor sodae, or water, which does equally well. A centimetre of urine is drawn into another pipette, and the number of drops which it contains is estimated, in the first instance, by allowing the fluid to escape guttatim from the pipette, by exercising gentle pressure on its indiarubber cap. No further measurement is required for that urine, as with the same pipette the number of drops will always be the same. The number of drops in 1 c.c. being ascer- tained — say, e.g., 24 drops — the urine pipette is again filled, and the 2 c.c. of ' Fehling ' are boiled, and its decoloration produced drop by drop by the saccharine urine. If 8 drops, e.g., are found to have decolorized the 2 c.c. of ' Fehling,' then this amounts to ^ of a c.c, and 2 c.c. of 'Fehling' correspond to 1 centigramme of glucose. Rule : Multiply the number of drops contained in 1 c.c. of urine by 10, and divide the product by the number of drops required to decolorize 2 c.c. of ' Fehling,' and the quotient will represent the number of grammes and centi-. grammes of sugar per litre (8 : 24 : : 1 : 3, and 3 x 1000= 3000-^100=30 grammes; i.e., if 1 c.c. of urine contain 3 centi- grammes, a litre must contain 30 grammes). Approximate Estimate of Sugar by Specific Gravity.— According to Bouchardat, the amount of sugar in urine may be approximately determined as follows : The density of the urine being determined by the urinometer, the two final figures above 1000 are multiplied by 2, and the number thus obtained, by the number of litres of urine voided in twenty-four hours. From this deduct 60, which represents the average quantity of solid matter other than sugar, and the remainder will represent the 172 THE URINE IN HEALTH AND DISEASE. amount of sugar in the volume of twenty four hours' urine. Supposing 4 litres of urine have been passed in twenty-four hours of a specific gravity of 1036, then 36 x 2 x 4=288 grammes, which represents the total solids in twenty-four hours' urine ; then 288 — 60=228 grammes of sugar, or 57 grammes per litre. Allowance has to be made for temperature. Gerrard's Percentage Glycosometer. — This instrument consists of a burette graduated to read the percentage of sugar, or grains per ounce, in urine, without the need of any calculation. Analysis. — Take either 10 drachms or 10 c.c. of urine which is found to con- tain sugar, and dilute with water to 100 drachms or 100 c.c. Mix well. Then introduce 10 c.c. or 2 \ drachms of Feh- ling's solution, and 40 c.c. (10 drachms) of water into the porcelain dish and boil. While the reagent is boiling, run the urine from the burette into the dish in a slow stream until the blue colour of the ' Feh- ling ' has disappeared. The level of the urine in the burette shows the percentage of sugar present, and the equivalent in grains is given in the annexed table. As the instrument is graduated to read per- centages between 10 and 1 should the urine contain more than 10 per cent, of sugar, dilute 10 volumes to 200 with water, , proceed as before, and multiply the per- centage by 2. If the percentage be less Yig. 36. Gerrard's than 1> undiluted urine is to be used, and Percentage Gly- the reading divided by 10. COSOMETER. ABNORMAL CONSTITUENTS OF THE URINE. 173 Table showing the Percentage equivalent in Grains per Fluid Ounce. • (jr£iins per Gr iins per Percentage. Fluid Ounce. Percentage. Fluid Ounce. 100 ... ... 4375 1-9 ... 8.3 9*5 41-55 1-8 ... 7-9 90 ... 394 1-7 ... 7-45 8'5 ... ... 37-2 1-6 ... 7-0 8-0 ... ... 35*0 1-5 ... ... 6-55 75 ... .. 32-8 1-4 ... ... 6-1 7-0 ... ... 30-6 1-3 ... . . 5-7 6-5 ... ... 28-45 1-2 ... ... 5-25 6-0 ... ... 26-25 1-1 ... ... 4-8 5*5 ... ... 24-05 1-0 ... ... 4-4 5-0 ... ... 21-9 •9 ... ... 3-95 4-5 ... ... 19-7 •8 ... ... 3.5 4-0 ... ... 17-5 '/ ... 3-05 3-5 ... ... 15-3 •6 ... ... 2-6 3-0 ... ... 13-1 •5 ... ... 2-2 2'5 ... ... 10-95 •4 ... ... 1-75 2-0 ... ... 8-75 Optical Quantitative Analysis. — This process is based on the property which sugar possesses of deviating the plane of polarization to the right. For aqueous solutions of sugar it is well adapted, but not for urine. As the result of numerous analyses by Worm-Miiller, he found that when urine contained more than 5 per cent, of sugar the polariscope gave lower figures. This depends, according to Kutz, on the fact that in grave forms of diabetes the urine contains oxybutyric acid, which is levogyrate and non-fermentable ; and, according to Seegen, the urine may contain levulose. This process is therefore more suited to the chemical laboratory than for the purposes of the clinician. Pathological Significance.— Sugar exists normally in the blood of man, in all the mammalia, and in almost all the animal series. In the condition of perfect health it disappears in the tissues by undergoing a process of oxidation, being thus con- verted into water and carbonic acid. The presence of a small quantity of glucose in the urine is held by some authorities 174 THE URINE IN HEALTH AND DISEASE. to be quite compatible with perfect health (physiological glyco- suria), but the proportion, according to Worm-Miiller, does not exceed from 0*025 to 0*5 per cent. According to Bouchard,* glycosuria appears when the blood contains more than from 4 to 6 grammes of sugar per kilo- gramme. Temporary or physiological glycosuria may be occasioned by the ingestion of large quantities of sugar, or of substances such as milk, starch, etc., capable of being trans- formed into sugar in the process of digestion (alimentary glycosuria). Of this nature is likewise the glycosuria observed in females after child-birth, in females nursing, and in certain pregnant females. The physiological sympathy between the uterus and mammae is disturbed ; and notably, when the secre- tion of milk is arrested, glycosuria appears ; while, conversely, if the secretion of milk be abundant, it is rarely found. Glycosuria may be a symptom of transient impressions on the system (symptomatic and toxic glycosuria), and is thus found in cases of poisoning by phosphorus, arsenic, carbonic oxide, curara, turpentine, nitrate of amyl, morphia (in large doses), chloral, chloroform, alcohol, hydrocyanic acid, mercury, etc. It is also found co-existent with such independent diseases as pneumonia, phthisis, yellow atrophy of the liver, thrombosis of the portal vein, chronic gastritis, malaria, cerebral tumours, and haemor- rhage, lesions of the brain and spinal column, psychical hyper- excitation, etc. These several conditions resolve themselves finally into impressions on the nervous system, some ill-defined aberrant condition being the primary factor in their causation. Idiopathic Glycosuria. — The most prominent feature of this condition is polyuria, with progressive emaciation. While emaciation is the rule, exceptional cases are sometimes en- countered in which the patient does not lose much flesh, when, indeed, a certain amount of embonpoint exists. In these cases it is found that the amount of urea in the urine is diminished, while in the former it is much increased. In such cases Garrod has found as much as 70 grammes of urea in the daily excretion of urine, with 226*46 grammes of sugar. * Maladies par Reltntissement de la Nutrition, 2nd edition, Pari?, 1885. ABNORMAL CONSTITUENTS OF THE URINE. 175 Diabetic urine, in addition to being abundant, is usually of a pale straw-colour, of a saccharine odour, often compared to the smell of violets, musk, etc., and of a high specific gravity, as a rule ranging from 1025 to 1050. When the quantity of sugar is less abundant, the specific gravity may descend to 1010. Uric acid and earthy phosphates are sometimes found in saccharine urine. After the lapse of from two to three days such urine undergoes fermentation, and is found to contain the Penicillium glaucum, and spores analogous to the ferment of beer, which decompose the sugar into alcohol and carbonic acid. On the drying of clothes which may have been saturated with saccharine urine, a white powdery deposit is left, which is often the first thing to attract the attention of the patient. The amount of glucose contained in the daily discharge of urine varies from 80 to 100 grammes on an average. Jaccond places it as high as 500 grammes, while in exceptional cases it reaches the high figure of 1,200 to 1,375 grammes (Lecorche, Fereol). The proportion of glucose is found to vary in the same individual according to the time at which it is excreted ; thus, the urine of the day contains more (muscular exertion no doubt contributing to this) than that of the night. In advanced diabetes the reverse is the case. Glucose reaches its maximum in the urine after food, and especially so if starchy constituents have been partaken of. In order to estimate, therefore, the amount of glucose, a specimen of urine should be taken from the combined amount passed in twenty -four hours. Nitrogenous diet and abstinence diminish the a.mount of glucose in the urine, and cane-sugar and starch augment it. Glycerine, saccharine, lactose, and levulose seem to exert no influence over it. Diabetic urine sometimes contains albumen, and this is doubtless due to the transitory irritation and hyperemia, as in the case of bile and other substances, which cause even the formation of tube-casts. Levulose and inosite often co-exist with glucose in diabetic urine, and occasionally dextrine almost entirely replaces glucose. Oxybutyric acid, acetone, and alcohol may also be found in diabetic urine. Oxybutyric acid deviates the plane of polarization 176 THE UKINE IN HEALTH AND DISEASE. to the left, and the error which may thus arise should be corrected by the use of Fehling's solution. Chloride of sodium is often diminished in quantity in diabetic urine. Phosphaturia, oxaluria, and azoturia may co-exist with, and sometimes take the place of, glycosuria. Therapeutic Indications. — Glycosuria appears to be due to some obscure disease of the nervous centres not yet well defined, and death ensues from debility, progressive wasting, and exhaustion. Consequently tonic treatment is indicated — iron, strychnine, arsenic, and phosphorus may be administered singly or in some of their numerous forms of combination, Easton's syrup being one of the best. The diet should be chiefly nitro- genous, and all saccharine and starchy food should be withheld. There is no objection to the administration of dry sherry in moderate quantity. Theoretically, peroxide of hydrogen and permanganate of potash have found favour in the treatment of glycosuria. Two or three grains of codeia, especially in combination with about half a grain of extract of belladonna, most markedly diminish the amount of the urine secreted, while these agents do not, however, diminish the specific gravity. Antipyrin is said to diminish the amount of sugar. Simulated Glycosuria. — For purposes of deception in the case of hospital patients and others, glycosuria is not un frequently simulated by the addition of cane-sugar to the urine. This fraud is easily detected, as such urine does not reduce Fehling's solution. The cane-sugar is usually added in excess, and the density of the urine is thus suspiciously increased (1070 and beyond). By heating this urine for a few minutes with a dilute acid, the cane is transformed into grape sugar, and Feh- ling's test may be applied. Again, the saccharimeter in the former case shows a right deviation, while the latter is levc- gyrate. Sometimes grape-sugar (raisin) is added. In this case the fraud is more difficult of detection. Grape-sugar as existing in commerce is never chemically pure, and contains products inter- mediate between grape-sugar and dextrine, possessing a right rotation. In a case of genuine glycosuria, the results obtained by chemical and optical analysis vary but to a trifling degree, ABNORMAL CONSTITUENTS OF THE URINE. 177 while if grape-sugar has been added to the urine, the chemical method gives a higher result than the optical. LEVULOSE, LACTOSE, INOSITE. Levulose, or Invert Sugar (C 6 H 12 0 6 ), is sometimes found in the urine of diabetic patients. Its behaviour with reagents is almost identical with that of glucose. It is uncrystallizable, and deviates the plane of polarization to the left. It undergoes fermentation, but less readily than glucose. A saccharine urine with left rotation usually points to levulose. It must be borne in mind in this connection that the ingestion of chloral, camphor, and benzene gives to the urine a like property, while it reduces copper in alkaline solutions. Levulose is also indicated when Fehling's solution shows a greater proportion of sugar than polarization does. Lactose, or Sugar of Milk (Saccharum Lactis, B.P. — C12H22O11), as already noted, usually exists in the urine of pregnant and nursing females, and children at the breast. It is the sweet principle of the milk of animals, and does not undergo the alcoholic or vinous fermentation. It crystallizes in oblique prisms, soluble in water, but insoluble in alcohol and ether. Its solutions are dextrogyrate. It resembles grape-sugar in reducing alkaline solutions of copper with precipitation of suboxide, but it has no effect on Barfoed's re- agent.* In order to prove its presence in urine it must be sepa- rated in the following manner : The urine is precipitated by a mixed solution of acetate of lead 37.— Lactose. and ammonia. The precipitate obtained is decomposed by sulphuretted hydrogen, and the hydrochloric acid liberated is neutralized by oxide of silver. After nitration the excess of silver is precipitated by carbonate of baryta. A crystalline mass is obtained by further filtration and concentration, which can be * A weak solution of acetate of copper with 1 per cent, of acetic acid. 12 178 THE URINE IN HEALTH AND DISEASE. crystallized after washing with dilute alcohol. It is distinguished, as already indicated, by reducing 4 Fehling,' and having no influence on Barfoed's reagent. Inosite (C 6 H 12 0 6 +2H 2 0). — This substance is isomeric with glucose, and is found in the muscles, in the lungs, in the kidneys, liver, brain, etc. It sometimes co-exists with glucose in the light. It is precipitated by basic acetate of lead. If a solution of inosite with nitric acid be evaporated to dryness on a platinum plate, the residue moistened with a little chloride of ammonium and chloride of lime, and carefully again evaporated, a beautiful rose coloration is produced (Scherer). Mercuric nitrate solution gives with neutral solutions of inosite a yellow precipitate. By carefully evaporating the liquid the precipitate becomes more or less red, the colour disappearing on cooling. As albumen behaves similarly, care should be taken that the urine contains none of it. If sugar be present, the coloration is black ; it also must be removed. Analysis. — The urine is treated by neutral acetate of lead, which separates the sulphates, chlorides, etc., boiled and filtered. The filtered liquid is then evaporated to about a fourth ; basic acetate of lead is again added, and a precipitate is obtained containing inosite. This precipitate is collected, washed with distilled water, then suspended in a fresh quantity of water, and Fig. 38. — Inosite. urine. It crystallizes in a rhomboidal form or pris- matic needles. It is very soluble in water, but is in- soluble in ether or absolute alcohol. It does not under- go alcoholic fermentation, but in contact with proteid animal matter it is con- verted into lactic and buty- ric acid. It does not become brown on boiling with liquor potassae, it does not reduce Fehling's solution, and is without action on polarized ABNORMAL CONSTITUENTS OF THE URINE. 179 decomposed by sulphuretted hydrogen. The resulting sulphide of lead is separated by filtration, the filtered fluid is concentrated by evaporation, and the inosite precipitated by the addition of concentrated alcohol. After repose the deposit acquires more or less coherence. It is then redissolved in distilled water, evaporated, a little concentrated alcohol or ether added, and crystallization allowed to take place. The tests of Scherer and Gallois may then be applied. Pathological Significance.— Inosite is found in the urine in most cases of polyuria. In thirty cases of diabetes and twenty- five of albuminuria, Gallois found inosite in seven — viz., in five of the former and two of the latter. o Cystine. Cystine (C 6 H 6 NS 2 0 4 ), first discovered by Wollaston in 1810 is sometimes found in a state of solu- tion in the urine. It is most frequently found in a sedimentary form, often in combination with urate of soda, and in the majority of cases in the form of a calculus. Cystine is found in the sub- > stance of the liver and kidneys. It is a O ^ remarkable fact that it is sometimes Fig. 39. — Cystine. found in several members of the same family, so as to constitute a distinct diathesis allied to the rheumatic. Characters and Properties. — Cystine is a substance rich in nitrogen and sulphur. It is colourless, inodorous, and entirely transparent, and crystallizes in hexagonal scales. It is insoluble in water, alcohol, and ether, but readily soluble in ammonia, unlike the somewhat similar crystals of uric acid. It is likewise soluble in solutions of potash, the mineral acids, and oxalic acid, but insoluble in tartaric and citric acids. Heated on platinum it decomposes, evolving a foetid odour, and burns with a greenish- blue flame ; heated on silver it causes a black or brownish stain of sulphide of silver. Cystine dissolves with the aid of heat in nitric acid ; on the solution being evaporated, a reddish residue is left, which is not affected by caustic alkalies. The presence of sulphur in cystine can be demonstrated by 180 THE URINE IN HEALTH AND DISEASE. solution in caustic soda, boiling for a few minutes, and adding a solution of oxide of lead : a black precipitate of sulphide of lead is obtained. The presence of nitrogen is shown by heating in a tube with a fragment of potash, when ammonia is evolved. If cystine be dissolved in a strong solution of boiling potash, and a weak solution of nitro-prussiate of soda be added, a beauti- ful violet colour results. Urine containing cystine is characterized by its pale colour, tendency to alkalinity, and, during putrefac- tion, by the exhalation of an odour of sulphuretted hydrogen. If it contain much cystine the specific gravity is high. Analysis. — To separate cystine dissolved in urine it is precipi- tated by acetic acid ; the precipitate is collected on a filter, and dissolved by means of ammonia. By evaporation of the ammoniacal solution, or the addition of acetic acid, the cystine crystallizes in characteristic hexagonal scales, when the tests above mentioned may be applied. Tyrosine and Leucine. Tyrosine (C 9 H n N0 3 ) and leucine are products of imperfect oxidation of albuminoid sub - stances.* Both bodies are found normally in the liver, pancreas, lymphatic glands, etc., and wherever albumi- nous substances under- go putrefaction, as in old cheese. Properties. — Tyro- sine is sparingly soluble in cold water ; it dis- solves in 150 parts of boiling water, and is insoluble in ether. It is difficult of solution in pure alcohol, but dissolves in ammoniacal alcohol, in acids, and caustic alkalies and carbonates. * Vide * Lectures on Bright's Disease,' by Author, p. 63. Fig. 40. — Tyrosine. ABNORMAL CONSTITUENTS OF THE URINE. 181 It does not sublime when heated, being thus distinguished from leucine, and decomposes with an odour of burnt horn. It crystallizes in the form of elongated silky needles, uniting in radiate form (Fig. 40). Evaporated on a platinum plate, it assumes an orange colour, and leaves a deep yellow residue, transformed into red by soda. Evaporated anew, the liquid becomes brownish -black (Scherer's reaction). If nitrate of mercury be added to a boiling solution of tyrosine, a flaky red precipitate is obtained, and the solution assumes a rose colour. If a few drops of tyrosine be mixed with a few drops of concentrated sulphuric acid in a capsule, gently heated, and a little water be added, a liquid is obtained which, neutralized with carbonate of baryta, gives with neutral per- chloride of iron a beautiful violet-red coloration. Pathological Significance. — Tyrosine does not exist in healthy urine. With leucine, it is found in the urine in cases of yellow atrophy of the liver, typhus fever, and small-pox, and in cases of poisoning by phosphorus, where the blood is sub- oxidized. In pernicious anaemia it has also been found, and here there is likewise sub oxidation from a deficiency of red cor- puscles. Microscopic examination most easily reveals the pre- sence of tyrosine and leucine. Leucine (C 6 H 13 N0 2 ), like tyrosine, is derived from organic constitu- ents rich in nitrogen. It is found, in like manner, normally in the liver, pancreas and spleen. Properties. — Pure leucine crystallizes in the form of successive thin plates. When impure, as found in clinical research, it presents the form of Fig. 41. — Leucine. 182 THE UBINE IN HEALTH AND DISEASE. small spherules, usually coloured, striated, and with jagged projections. Gently heated to 170°, it sublimes in a flaky cloud, and is thus distinguished from tyrosine. If the tem- perature be elevated to 180°, the leucine is decomposed, leaving a liquid from which amylamine (C 10 H 13 N) crystallizes out on cooling. Evaporated on a platinum plate with nitric acid, leucine leaves a spare, colourless residue, which, treated with a few drops of caustic soda, dissolves on being heated, giving a colourless or yellow fluid, which, again, on evaporation, forms an oily globule, which rolls about, and does not tarnish the platinum. Pathological Significance. — Leucine exists in the urine in cases of yellow atrophy of the liver. Analysis. — Tyrosine and leucine are usually found in the urine in the state of solution. Leucine is always in smaller quantity than tyrosine. To separate these constituents from the urine, if it be albuminous, the albumen must first be removed by coagulation and filtration. The filtrate is then precipitated by basic acetate of lead. This is again filtered, and the excess of lead removed by a current of sulphuretted hydrogen. Filtration is again resorted to, and the filtrate evaporated. After a brief repose tyrosine deposits. This deposit may again be dissolved in boiling water, allowed to crystallize, and examined micro- scopically, or with the above-mentioned reagents. To separate leucine, the fluid from which the tyrosine has been obtained is evaporated to dryness, treated at first with cold and then with boiling alcohol. The alcoholic solution thus obtained is evaporated to a syrupy consistence, and after a short time's repose the leucine separates in its characteristic spherical form. The leucine is yet impure, and should be purified as follows before applying chemical tests : Dry the leucine between two sheets of filter paper, dissolve in ammoniacal solution, and precipitate the solution by neutral acetate of lead. Filter ; suspend the precipitate in water, and decompose by sulphuretted hydrogen. Concentrate the filtered fluid by evaporation, and set aside for crystallization. In the form of a sediment tyrosine is recognised in the following manner : The sediment is collected on a filter, washed with water, and dissolved in ammonia with the addition of a little carbonate of ammonia. Crystallize by evaporation, and examine microscopically and chemically. ABNOBMAL CONSTITUENTS OF THE URINE. 183 ACETONE. History of Acetone — Properties — ChautarcTs Test — Orthonitrobenzal- dehyde Reaction —Extraction of Acetone from Urine — Quantitative Analysis — Pathological Significance — Various forms of Acetonuria. Acetone (C 3 H 6 0) is often found in diabetic urine (acetonuria), being first discovered in this fluid by Peters.* It is most usually found in the urine in the advanced stages of diabetes. It is also found in a considerable number of febrile affections, as in scarlatina, pneumonia, and cancerous affections of the digestive organs ; and in leucocythaemia, pernicious anaemia, Addison's disease, etc. Urine containing acetone emits a peculiar odour like that of chloroform, is usually scanty, and of high specific gravity. In proportion to the abundance of acetone, that of glucose is inversely diminished. The breath also has the characteristic smell of acetone, especially in the last stages of diabetes. According to Jaksch, acetone exists in feeble quantity in normal urine (0*01 or more in twenty-four hours). Properties. — Acetone is a clear liquid of a density of 0*814, boiling at 56° C, inflammable, and of an agreeable odour (like acetic ether), and mixes in all proportions with alcohol and ether. Submitted to the successive influence of a concentrated solution of iodine in iodide of potassium and of caustic soda, it forms iodo- form, which separates in microscopic hexagonal tablets, or in stars of six arms, of a yellow colour and disagreeable odour (Lieben's reaction). Alcohol, according to Jaksch, gives the same reaction, but with it the iodoform forms much less rapidly than with the acetone. Acetone may be obtained by the distillation of acetate of soda, or a mixture of acetate of lead and of lime. The condensed liquid is brought under the action of chloride of lime, and then distilled on a water-bath. The distillate is collected. This is again brought in contact for several hours with lime, then dis- tilled anew, collecting only what passes at 56° C. Acetone com- bines with bisulphite of soda, forming a crystalline compound. In 1864 Gerhardtf demonstrated that certain urines containing * Vierteljahrschrift fur de Pract. HeilJcunde, Prague, 1857. f Gerhardt, Wiener Medicinische Presse, vol. iv., p. 28. 184 THE UKINE IN HEALTH AND DISEASE. sugar were coloured red by the addition of perchloride of iron. Until recently it was believed that this coloration was due to the acetone contained in the urine ; and certain of the phenomena of the comatose state, in cases of diabetes, were attributed to this principle. Von Jaksch subsequently arrived at different con- clusions from Gerhardt, and he proved that the reaction described by Gerhardt was produced by acetylacetic acid, while with re- gard to the acetone, it was necessary for its detection to employ a special method. Urine containing sulphocyanide of potassium is also coloured red by perchloride of iron. The reddish-brown colour produced by sulphuric acid in urine containing acetone is also equally fallacious, as it is likewise pro- duced in urines which do not contain this principle. The same applies to the reaction of Lieben. The following tests are, how- ever, reliable. Chautard's Test.* — Dissolve 0*25 gramme of fuchsine in 500 grammes of water, through which pass a current of sul- phurous acid until the yellow colour disappears. This solution (sulpho-rosanilinic reaction) may be kept indefinitely in stoppered bottles. With a tenth part of acetone, this reagent gives an intense violet colour, with 4^th a similar colour, and with iTnnrth a sufficiently appreciable colour. When the amount of acetone is small, 200 c.c. of the urine may be distilled, and the first 15 c.c. of the distillate may be tested. Orthonitrobenzaldehyde Reaction. — This test, of great sensibility, has been recommended by Baeyer and Drewsen. A few crystals of orthonitrobenzaldehyde, which, being explosive, must be carefully handled, are boiled with a little water, and the solution allowed to cool. To the first products of the distillation of the urine, rendered alkaline with a soda solution, some of the above solution is added. After about six minutes, if the urine contain acetone it becomes yellow, then green, and finally pre- cipitates indigo. If the acetone be only in small quantity, the yellow fluid is to be agitated with chloroform, and after a short time the indigo colour ensues. Otherwise, prepare ready for use a 5 per cent, solution of nitro-prussiate of soda and a 30 per cent, solution of caustic * Bu'letin de la Socie'U Ghimique, t. 45. ABNORMAL CONSTITUENTS OF THE URINE. 185 potash. To the first portion of the distillate a few drops of each of these solutions are added ; boil, and add a few drops of acetic acid by pouring gently along the tube wall so as to prevent admixture. At the point of junction of the fluids a beautiful red colour is produced. The successive addition of the foregoing solutions even without acetic acid causes a pronounced red colour with acetone. If then acetic acid be added and the fluid boiled, the red colour is changed into green. According to Weyl, creatinine gives the same reaction.* To extract Acetone from the Urine. — Von Jaksch recom- mends that almost a litre of this fluid should be acidulated with hydrochloric or tartaric acid, ether added and distilled. The acidulation prevents cloudiness, and the passing of carbonate of ammonia into the distillate. To the latter is added a small quantity of iodine, dissolved by means of iodide of potassium, and finally caustic potash. The result is, according to the amount of acetone, either a precipitate or an opacity due to the formation of iodoform (Lieben's reaction). Iodoform is recog- nised by its odour, by its volatilization on being heated, and by its crystalline form. In order to obtain it in this form the liquid containing the iodoform is agitated with ether, which spontaneously evaporates, and the crystals subside. Quantitative Analysis of Acetone. — Salkowskif and Taniguti employ the following process : To 300 c.c. of urine add 10 c.c. of concentrated sulphuric acid, and distil. To the distillate add soda or potash lye, then the iodine solution, and set aside for twenty-four hours. Filter, collect the iodoform, and weigh. J Pathological Significance. — It has been observed that the breath of diabetic patients is characterized by a vinous odour. This has in recent years been proved to be due to the presence of acetone (acetonemia) in the blood. According to Lieben,§ acetone exists to the extent of about 1 centigramme in the urine of twenty-four hours ; but in certain pathological states the * Acetone reduces Fehling's Solution. f Zeit.fur Physiol. Chemie, xiv., 1890, Heft 5. J Vide Annal. des Mai. des Organ. Genito-Urin., No. 9, 1892. § Lieben, Annates der Chemie und Pharmacie, p. 236, 1870. 186 THE UBINE IN HEALTH AND DISEASE. quantity amounts to as much as 50 centigrammes per diem. This pathological condition, to which the name of hyper- acetonuria has been given, was observed under four different conditions : First, fever, from whatever cause ; secondly, in diabetes ; thirdly, in certain cases of cancer ; fourthly, in patients suffering from an affection to which Kaulich and Cantani gave the name acetonemia. First Form. — If in any patient the fever attains to a high degree, hyper-acetonuria appears. The most varied affections present this phenomenon. Second Form. — Independently of numerous cases of diabetes in which acetone is not in excess, there are two varieties : First, the cases in which acetone is in excess ; secondly, the cases in which acetone is in excess, and in which the urine gives Gerhardt's reaction. In these cases the affection is grave, and death is usually ushered in by coma. Third Form. — Acetonuria occurs in certain cases of carcinoma. The cause is unknown. Fourth Form. — In the acetonuria of Kaulich and Cantani acetone is found in excess in the urine. Perchloride of iron in these cases invariably gives a red reaction. Gerhardt's reaction is seldom given in grave diabetic acetonuria. Acetone and acetylacetic acid are far from being independent in every case. Siefert* believes that the appearance of acetone in the urine is due to the ingestion of alcohol. Like Jaksch, he observed the reaction in various febrile disorders, and distinguished certain new features of it, differentiating it from other reactions of a similar kind. The constituent thus discovered in the urine would be, according to this authority, not acetylacetic acid, but acetylacetate of ethyl, which in decomposing gives origin to acetone, the accumulation of this substance in considerable quantity in the organism exercising, according to Siefert, a depressing action on the cerebral functions. Brieger has demonstrated that it required at least 2 grammes of acetylacetate of ethyl to a litre of urine to obtain the reaction of Gerhardt. In another series of experiments, 20 grammes of * Physikalisch- Medicinhche Getsellschaft, Wurzburg, vol. xvii., No. 4, i882. ABNORMAL CONSTITUENTS OF THE URINE. 187 acetylacetate of ethyl per diem were given to perfectly healthy men and to a diabetic patient without Gerhardt's reaction having been obtained.* Melanine. In certain cases of melanosis this pigment appears in the urine, which when emitted is clear, but gradually becomes of a deep brown, or even black, colour. Ordinarily melanine exists in solution in the urine, but some- times in the form of a brownish or black sediment, recognisable by microscopic examination. Melanine may possess a diagnostic significance, when the melanosis is beyond the reach of examina- tion by eye or touch. It may disappear from the urine when the disease is arrested, or remain stationary. Oxidizing agents, such as chromic acid and fuming nitric acid, transform the principle melanine, causing gradually with the first and imme- diately with the second a black coloration. According to Zeller, the most delicate test for melanine is bromine water. With melanine it gives at first a yellow precipitate, which gradually blackens. Urobiline gives a yellow precipitate with same reagent, but it does not blacken. Diverse Acids. The following acids are occasionally found in the urine : Lactic Acid (C 3 H 6 0 3 ) is found in the urine in cases of poisoning by phosphorus, yellow atrophy of the liver, and mollities ossium. It is probably derived from the fermentation of saccharine and amylaceous substances. Formic Acid (HCH0. 2 ), so called from the fact that it is ejected from the red ant when irritated, is found in the urine in cases of leucocy- thaemia. Valerianic Acid (HC 5 H 9 0 2 ) is found in the urine in cases of typhus fever, small-pox, and yellow atrophy of the liver. Acetic (HC 2 H 3 0 2 ) and Propionic Acid (C 2 H 5 COOH) are found in cases of diabetes after the urine has undergone fer- mentation. Lehmann found Butyric Acid (HC 4 H 7 0 2 ) in the urine of females after childbirth. * Vide 1 Considerationes sur le diabete Acetonemique,' par J. Cor- nillon et A. Mallat {Le Progres Medical, April, 1886). 188 THE URINE IN HEALTH AND DISEASE. BILE ELEMENTS. Bile Elements — Mucine of Bile — Biliary Pigments : Bilirubine, Bili- verdine, Biliprasine, Bilifuscine, Bilihumine — Detection of Colouring Matter of Bile in Urine— Gmelin's Reaction — Analysis — Rosen- bach's Modification of Gmelin's Test— Huppert's Reaction — Bile Acids : Choleic or Taurocholic Acid, Glycocholic Acid, Cholalic Acid — Reaction of Bile Acids (Pettenkofer's Reaction) — Cholesterine — — A nalysis — Pathological Significance. When secreted by the liver bile is a yellow fluid, of a density varying from 1020 to 1035. According to the length of time which it remains in the gall-bladder, it becomes of a deeper brown colour. It contains no albumen. On being treated with alcohol, the mucine which it contains is precipitated. Of all the fluids of the system it is the densest, a tenth of its weight consist- ing of solid matter — chiefly biliary pigments, acids, mucine, and cholesterine. Mucine of Bile. — In addition to its acting as a reservoir for bile, the gall-bladder adds to the bile its special secretion — mucine. Bile as it exists in the hepatic canals does not, there- fore, contain mucine. This constituent may be separated from bile by treating it with four or five times its volume of alcohol. Biliary Pigments. — The colouring pigments of the bile are : Bilirubine (Ci 6 H 18 N 2 0 3 ). Biliverdine (C 16 H 18 N 2 0 4 ). Biliprasine (Ci G H22N 2 0 G ) . Bilifuscine (C 16 H 2 oN 2 0 4 ). Bilihumine. — Atomic composition not yet determined. All the four latter of this group of substances appear to be derived from the former by oxidation. Bilirubine (C 16 H 18 N 2 0 3 ) is found in the bile in small quantity in combination with alkaline bases. It is almost the sole constituent of certain biliary calculi. It may be removed from bile or bilious urine by the addition of hydrochloric acid and agitation with chloroform. It may be obtained from calculi containing it by first treating them with ether to remove the fatty matter and cholesterine which they contain ; the salts are then dissolved out by boiling water, and the residue treated with hydrochloric acid and chloroform, in which the ABNOKMAL CONSTITUENTS OF THE URINE. 189 bilirubine is dissolved. This solution by evaporation deposits an mpure bilirubine. On this being treated with alcohol and ether, bilifuscine and fatty matter' are removed ; the remainder may then be crystallized from chloroform. Bilirubine appears in the form of an amorphous or ange - coloured powder. Crystallized from the chloro- form solution, it forms rhom- boidal microscopic prisms. It is insoluble in water, spar- ingly soluble in alcohol and ether, very soluble in chloro- form, benzene, and bisulphide of carbon. The solutions are yellow, and are precipitated by soluble metallic salts, the bili- rubine forming combinations with the oxides of the metals, which are insoluble in water and chloroform. Bilirubine is soluble in caustic alkalies, in which, by the absorption of oxygen, it is converted into biliverdine. Biliverdine (C 16 H 18 N 2 0 4 ) is a product of the oxidation of bilirubine. It may be obtained by exposure of an alkaline solution of bilirubine to the air in a wide-mouthed bottle, and shaking from time to time. Finally it transforms into bili- prasine. When the green colour due to oxidation has ceased, the solution is precipitated by hydrochloric acid. The precipitate is washed with boiling alcohol, which dissolves the biliverdine alone, from which it separates on evaporation as a greenish residue. Biliverdine is amorphous, of a deep green colour, in- soluble in water, ether, and chloroform, but soluble in alcohol and alkalies, the solution being of a green colour. Biliprasine (C 16 H 22 N 2 0 6 ) is derived from biliverdine by the addition of two molecules of water. It is found in small quantity in biliary calculi, from which it may be extracted by treatment with water, hydrochloric acid, ether, and chloroform, so as to remove the substances soluble in these agents, the biliprasine being left as a residue. From this residue it is dissolved by alcohol, in which it is easily soluble, the solution being of a green colour, becoming brown by the addition of Fig. 42. — Bilirubine. 190 THE URINE IN HEALTH AND DISEASE. ammonia. It is soluble in alkalies, and the brown solution is converted into green by the addition of acids. It is insoluble in water, ether, and chloroform. Bilifuscine (Ci 6 H 20 N 2 O4) is a deep-brown powder, amorphous, almost insoluble in water, ether, and chloroform, but readily soluble in alcohol, ammonia, and soda, giving a deep-brown solution. It accompanies bilirubine in biliary calculi, and is dissolved from them, or from bile, when they are treated with chloroform and hydrochloric acid. It separates from bilirubine on being treated with alcohol, in which bilirubine, as we have seen, is insoluble. Bilihumine, a constituent found only in biliary calculi, is of a brown earth {humus) colour. Its composition is not yet deter- mined. It remains as a residue when biliary calculi have been successively treated with w T ater, alcohol, ether, chloroform, and hydrochloric acid. It is therefore insoluble in these agents. It is soluble in caustic soda and ammonia, and is precipitated from their solutions by hydrochloric acid. Other products of the oxidation of bilirubine, such as bili- cyanine or choloverdine, and choleteline have been described. Detection of Colouring Matter of Bile in the Urine.— The mere aspect of bilious urine affords an indication as to the particular pigment present. Thus, if bilirubine predominates, the mine is yellow ; if biliverdine, it is greenish. Such urine stains linen or blotting-paper immersed in it, and on being agitated gives a yellow froth. Urine passed after the ingestion of senna, rhubarb, and santonine presents the same peculiarity, but these may be distinguished by their characteristic reactions. Gmelin's Reaction. — If to a solution of the foregoing con- stituents a little nitric acid be added, the liquid at first assumes a green colour, then blue, subsequently violet and red ; and at the end of some seconds, if the acid be in excess, the red colour disappears, and the liquid becomes yellow. If a solution of the pigments be poured on nitric acid so as to prevent mixing of the fluids, the various colours appear simultaneously in superposed layers, the green being uppermost. The green colour alone is characteristic of the bile pigments. Analysis. — Urine containing bile pigments is of a more or less ABNORMAL CONSTITUENTS OF THE UBINE. 191 yellow colour ; or it may be brownish, reddish-brown, or green, according to the predominating pigment. When the urine is yellow, bilirubine predominates ; when it is green, biliverdine. Linen and blotting-paper are stained by such urine, corresponding to the colour, and agitation causes a coloured froth. Into a conical vessel gently pour two or three c.c. of nitric acid which has been more or less exposed to air, then, by means of a pipette, place over it, without admixture, a little of the urine. If it contain bile pigments, there will be produced at the point of contact of the two liquids a green ring of more or less thickness, and below this violet, red and yellow rings. Indican gives with nitric acid the blue and red coloration ; but the green is characteristic of bile pigments. In order to identify bile pigments in sediments, such as urates, dissolve these sediments in carbonate of soda and test as above. The presence of albumen does not interfere with this reaction, if the colouring matter be not in very minute quantity. Rosenbach's Modification of Gmelin's Test. — Filter a given quantity of urine, then moisten the inner surface of the filter, still moist, with nitric acid. Concentric zones of green, blue, violet, and reddish-yellow then appear on the paper if bile salts be present. Bilious urine mixed with a drop of nitrate of soda solution and a little dilute sulphuric acid assumes a beautiful green colour. After some time the green disappears, and is replaced by yellow, without passing through the stages of red and blue. If a few drops of tincture of iodine be added to bilious urine, at the point of contact of the fluids a beautiful emerald- green colour appears. Bromine water produces the same result. Bilirubine may be isolated from bilious urine in the following manner : Into a small flask pour 100 c.c. of urine and 10 c.c. of chloroform, and gently mix the two liquids. Invert the flask, still closed, gently open the mouth of the flask, and allow the chloroform emulsion alone to pass out, and apply Gmelin's reaction. Huppert's Reaction. — Add to the urine a little ammonia and chloride of lime. If it contain bile pigment, a precipitate con- taining bilirubine is formed. This precipitate may be separated 192 THE URINE IN HEALTH AND DISEASE. by filtration, washed, and, while still moist, treated with strong alcohol containing sulphuric acid. On being heated the liquid will become of an emerald-green or greenish-blue colour. Ehrlich recommends the following process to identify bili- rubine alone : Mix a given quantity of urine with an equal volume of dilute acetic acid, and then add, drop by drop, a solution of sulphodiabenzol (one part of sulphanilic acid in 1,000 parts of water, with 15 c.c. of hydrochloric acid and 0*1 nitrate of soda). If the urine contains bilirubine, the mixture assumes the violet colour characteristic of this constituent. When the bile pigments are decomposed, exist only in small quantity, or when the urine contains indican, these processes are inapplicable. In such cases the bile pigment must be isolated ; to effect this render the urine alkaline by soda lye, then mix with chloride of barium or of lime, when a yellow precipitate forms. Filter, and boil the precipitate with alcohol containing a few drops of sulphuric acid, when the liquid assumes a beauti- ful blue colour. Bile Acids. According to Dragendorff, biliary acids are contained in normal urine in the proportion of 0*8 gramme to 100 litres.* These acids are, however, most frequently found in pathological states, united to the bile pigments. The two acids which exist in human bile under the form of soda salts, viz., choleic or tauro- cholic acid, and cholic or glycocliolic acid, are combinations of a third acid, cholalic acid, with taurine on the one hand, and glycochole on the other. Choleic or Taurocholic Acid (C^H^NSO-j) is a white amor- phous powder, soluble in water, alcohol, and chloroform, and insoluble in ether. Its solutions are dextrogyrate. Boiled with potash or hydrochloric acid for some hours, it is resolved into cholalic acid and taurine. Glycocliolic Acid (C^H^NO^) crystallizes in fine needle- prisms, which are colourless, and do not contain sulphur, by * Annal. des Mai. des Organ. Uenito-Ur'm., No. 8, 1892, p. 647. ABNORMAL CONSTITUENTS OF THE URINE 193 which they are distinguished from choleic acid. It dissolves with difficulty in cold, but readily in boiling, water and in alcohol. It is sparingly soluble in ether. On boiling with potash or hydrochloric acid it is resolved into cholalic acid and glycochole. Cholic Acid (C. 2 .iH 40 O 5 ) exists in the urine only in combination with taurine and gly- cochole, with which it forms the two pre- ceding acids. It crystallizes in four or six sided prisms. It is insoluble in water, very soluble in alcohol, sparingly soluble in ether. Its solutions are dextrogyrate. Boiled with mineral acids, it loses water Fig. 43. — Glycocholio and is transformed into dyslisine (CoiH^Ai). Reaction of Bile Acids (PettenJcofer'a Head Ion). — This is the test most frequently employed, and is as follows : To a solution of the foregoing acids add a few drops of a weak solution of sugar, a little concentrated sulphuric acid, and heat to a temperature not exceeding 60° C, when a violet -purple colour is obtained. Neukomm renders the reaction more delicate by the following procedure: Mix in a porcelain capsule a solution of bile-acids with a drop of dilute sulphuric acid, and a drop or two of sugar solution ; heat on a water-bath, when a beautiful violet- purple colour appears. The bile- acids may be isolated as follows: Evaporate a con- siderable quantity of urine on a water-bath almost to dryness. Then extract by alcohol, and with precaution evaporate anew. Dissolve the residue in a few drops of water and apply Petten- kofer's test. Kthe urine contain albumen it must be separated. Cholesterine. — The presence of cholesterine in the urine is very rare. It is found in cases of chyluria and fatty degenera- tion of the kidney, sometimes in the form of a sediment, and as a constituent of certain calculi. Cholesterine (C. 2 5H 43 HO), crystallizes in rhomboid scales, or in the form of fine needles. It is insoluble in water, dilute acids, alkalies, and cold alcohol, but soluble in boiling alcohol, ether, and chloroform. It may be extracted from gall-stones by boiling 13 194 THE UKINE IN HEALTH AND DISEASE. alcohol, from which it deposits on cooling. If a little choles- terine be dissolved in 2 c.c. of chloroform, and about the same volume of sulphuric acid be added, the liquid agitated, and then allowed to repose, the supernatant chloroform solution is found at first to be of a blood-colour, then cherry-red or purple, while the sulphuric acid becomes intensely green. If a little of the chloroform solution be put in a porcelain capsule, it undergoes rapid coloration from blue to green and yellow. Analysis. — To identify cholesterine in the urine, agitate with ether, decant the fluid, and evaporate. Treat the residue with Fig. 44.— Cholesterine. ammonia, to an ethereal solu- tion of cholesterine in a porcelain capsule, and a red coloration is the result. A solution of iodine and a drop or two of sul- phuric acid causes a greenish-blue coloration, changing to violet. Pathological Significance. — When bile is prevented from flowing into the intestines from any cause whatever, such as active or passive hyperemia of the liver, as from alcohol, obliteration of the biliary canals by calculi, catarrhal inflamma- tion of these canals, extending to the lobules of the liver, inflam- mation of the gall-bladder, its compression by a tumour, inter- stitial hypertrophy, as in phosphorus - poisoning, oedema of Glisson's capsule, etc., the bile is reabsorbed, and passes into the circulation. This is made manifest by the yellow colour im- parted to the various tissues of the body, and notably the con- junctiva. Bile elements are then eliminated by the kidney, and are found in the urine. alcohol, add a little potash, and boil for some time on a water- bath. Treat the residue with water, and agitate with ether. Evaporate the ethereal solution, redissolve the crystals in boiling alcohol, filter, and allow crystal- lization to take place. Add, drop by drop, strong sulphuric acid, or nitric acid and ABNORMAL CONSTITUENTS OF THE URINE. 195 Fatty Matter. Lipuria, Chyluria, Galacturia.*— Cases of chyluria may be grouped as follows : Chyluria properly so called, when it depends or not on parasites. The parasitic form of chyluria is found in tropical climates, and is caused by a round worm, the Filaria sanguinis hominis. The passing of the parasite from the blood to the kidney causes chyluria and hematuria. The urine necessarily contains albumen in — Advanced Fatty Degeneration of the Kidney, or of other portions of the urinary tract, as in cases of phosphorus-poison- ing. The bursting of an old abscess, and the consequent admixture of urine and pus may cause chyluria. Phthisis, prolonged suppurations, and all grave constitutional diseases, may cause chyluria. Chyluria has been observed after the ingestion of large quantities of aliment rich in fat, or after the experimental in- jection of oil into the bloodvessels. The fat presents itself under the form of more or less voluminous drops, which float to the surface (lipuria), or in a state of fine division, as in milk (galacturia). In the former case the urine appears as if it con- tained pus. In the case of pus, however, a deposit takes place, and a clear supernatant fluid remains, while the fatty urine retains its opacity. Detection of Fat in the Urine. — On microscopic examina- tion fat is observed in the form of fine granulations or small drops, of greater or less size, with dark contour, a brilliant centre, and very refractive. Chemically, the following reactions take place with fat : On being heated, a characteristic odour of acrolein is given off. On the addition of chloroform or ether, or sulphide of carbon, the urine becomes more or less clear. If the urine be poured on white paper, fatty stains may be observed. Lecithine and cholesterine, which are of a fatty nature, may also be found in the urine. * Vide ' Annal. des Mai. des Orgs. Genito-Urin.,' No. 2, 1893, p. 124. 196 THE URINE IN HEALTH AND DISEASE. Pathological Significance. — Lipuria most frequently occurs in fatty degeneration of the kidney, in cases of poisoning by phosphorus, in phthisis, pyaemia, gangrene, acute atrophy, and fatty degeneration of the liver, carcinoma, and prolonged suppurations, especially in connection with bones and joints. By tube-casts are understood microscopic moulds of the uriniferous tubes of the kidney, resulting from inflammation of the organ. This inflammation may be chronic and incurable, as in advanced Bright's disease, or may be due to transitory irritation of the organ from the elimination of certainirritants. These casts may be classified as : (1) True cylinders or casts (cylinders of destruction), comprising the following granular cylinders, viz., granular, granulo-fatty, fatty and mixed, amyloid tube-casts ; (2) Cylinders of exudation — hyaline cylinders ; (3) Tube-Casts. Fig. 45. —Fatty De- generation of Tubes from the Cortical por- tion of the Kidney in a Case of Phosphorus Poisoning (Phosphoric Steatose). — Ranvier. Fig. 46. — Longitudinal Sec- tion of the Tubular Substance of the Kidney in a Case of Albuminous Nephritis due to Poisoning by Phosphorus. The Loops of Henle are more altered than the straight tube be- tween them. ABNORMAL CONSTITUENTS OF THE URINE 197 Cylindroids — cylindroids, pseudo-cylinders, epithelial cylinders, hemorrhagic cylinders, and spermatic cylinders. Granular Cylinders. — This form of tube-casts presents an entirely granular aspect. They are less transparent than the amyloid and hyaline casts, and are generally larger. Some- times they are short, and of considerable diameter. They pre- sent either a regular or irregular outline. Their extremities are rounded, like the finger-tip, or serrated. They are composed of the debris of red globules, of leucocytes, and of epithelial cells, which have undergone more or less degeneration. Granulo -fatty cylinders may be regarded as the foregoing with fat globules superadded. They are found in Bright' s disease. Pure fatty granules are found only in cases of poison- ing by phosphorus. Mixed cylinders are combinations of the foregoing. Amyloid Casts or Cylinders.— These cylinders are of homo- geneous structure, are more refractive than hyaline cylinders, and are thus more denned in the microscopic field. They present a dull, waxy appearance. Ordinarily, they are short, and of greater diameter than the granular cylinders. Their contour is regular and smooth ; sometimes notched. They are sometimes twisted on themselves in the form of a corkscrew. They resist the action of acetic acid, and are insoluble in heated urine, and in distilled water. Osmic acid imparts to them a dark-brown colour. Iodine colours them yellow, and carmine imparts to them a deep red colour. Sulphuric acid renders them green. These cylinders seem to be composed of an altered protoplasm of the uriniferous tube-cells. Hyaline Cylinders. — These casts are homogeneous, pale, transparent, with ill-defined outline, flexible, of varying length, with defined or serrated extremities, and of a uniform diameter throughout their entire length as a rule. Sometimes they are broken into parts, and present the corkscrew appearance. Dilute acetic acid causes these cylinders to shrink, and they dissolve in strong acetic acid. Heated in the urine to 70° or 80° C, they dissolve, or heated to 30° or 40° C. in distilled water. They are soon destroyed in alkaline urine. The aspect 198 THE UEINE IN HEALTH AND DISEASE. of these casts is frequently altered by the deposition on them of diverse elements from the kidney, such as granulations of urates, of phosphates, crystals of oxalate of lime, fatty drops, round cells, blood- corpuscles, etc. Cylindroids (Pseudo- Cylinders).— These ele- ments (the mucous cylin- ders of Cornil and Ean- vier) appear as simple filaments, or as 1 ribbons ' of irregular outline and unequal diameter. Their surface is striated, and their extremities denti- lated. Their substance is transparent and colour- less, and they are' difficult to distinguish without the aid of staining agencies. Like other casts, their substance may have in- corporated with it other elements, such as fat- drops, albuminous granu- lations, blood-corpuscles, leucocytes, epithelial cells, etc. They present a wavy appearance. Dif- ferent salts, especially urates, are sometimes deposited in the uriniferous tubules, and are thus eliminated in the form of cylindrical masses. These may be readily distinguished by heating them on a glass slide, with a drop of hydrochloric acid, when crystals of uric acid will form. Spermatic Cylinders.— These are composed of casts from the prostatic ducts, and are found in cases of chronic prostatitis Fig. 47.— Hyaline Cylinders in a Case of Albuminous Nephritis. 1, Desquamated Renal Cells ; 2, Hya- line Cylinder with jagged edges ; 3, Hyaline Cylinder with fragments of cells adhering, and occasioning a granular ap- pearance ; 4, Hyaline Cylinder covered with fatty granulations ; 5, Hyaline Tube, of which the smaller portion seems to correspond to the intermediate, or canal of union. PLATE I. 4 6 Fig. 1. — Amyloid Cast treated with Osmic Acid. Fig. 2. — Colloid or Hyaline Cast without any Reagent. Fig. 3.— Colloid or Hyaline Cast treated with Osmic Acid. Fig. 4. — Mucous or Granulo-Fatty Cylinder. Fig. 5. — Fatty Casts treated with Osmic Acid. Fig. 6. — Granulo-Fatty Casts. [To face page 198. ABNORMAL CONSTITUENTS OF THE URINE. 199 and spermatorrhoea. These casts are hyaline, and resemble more or less renal cylinders.* Fig. 48. — Spermatozoa and Peostatic or Spermatic Casts. Epithelial Cylinders. — These cylinders, according to Lecorche, are formed of small polygonal cells, which can come only from the ' collector tubes ' of the kidney. They are com- posed of the desquamated surface of the straight tubes, and possibly of the descending limb of the loop of Henle. These casts are really very rare, and must not be confounded with mucous or granular casts, which present masses of epithelial cells. Their semeiological significance points to catarrhal irrita- tion of the straight tubes. Haemorrhagic Casts. — These casts are composed of red and white blood globules, united by fibrine, and are of medium dia- meter. It is rare to find the red globules intact. Generally they present an annular form, and have lost their colouring matter. Pathological Significance and Diagnostic Value. — The presence of tube-casts indicates inflammation more or less acute, acting especially upon the secretory structure of the kidney. This inflammation may be idiopathic, as in cases of Bright's disease, or may be due to the action of irritants and poisons on * Vide 6 Prostatic Casts,' by D. Campbell Black, M.D. (Lancet, January, 1866), and ' Annales des Malad. des Organes Genito- Urinaires,' 1887, p. 329. 200 THE URINE IN HEALTH AND DISEASE. the renal structure, such as cantharides, strong diuretics, bile, phosphorus, etc., or secondarily, from the elimination of the ' poisonous debris ' of such diseases as scarlatina, during the desquamative stage, small-pox, typhus, etc. Urinary cylinders are never wanting in acute nephritis and amyloid degeneration of the kidney. Casts are found in the urine of animals which have been covered with varnish and thus rendered albuminuric. Epithelial cylinders indicate desquamative nephritis. If pus corpuscles be found superadded, the prognosis will be less favour- able, as a greater intensity of inflammation is thus evident. Blood-casts indicate intense inflammation, or effusion of blood into the parenchyma, or calyces of the kidney. Granulo-fatty cylinders give evidence of fatty degeneration of the kidne} T , especially if associated with epithelial cells — Bright's disease in its second stage. Amyloid cylinders point to sclerosis of the kidney. Hyaline and granular tubes, especially if abundant, indicate chronic Bright's disease — the small red granular kidney. They are formed in tubes denuded of epithelium. The urine is often in excess of the quantity secreted in health, and as the solid constituents of the urine are inadequately eliminated, the specific gravity of the urine is as low as from 1010 to 1005.* In cases of cancer of the kidney the epithelial cells found in the urine are large, irregular, and present prolongations, or processes, with one or more nuclei. According to Aufrecht,f tube-casts may be due to an exudation from the blood, or be the product of the renal epithelium. He cites the following facts in favour of the latter view : (1) In certain experiments he tried one ureter, when the renal epithelium was seen to contain masses of a hyaline substance, which subsequently made its way into the lumen of the tubules to form casts ; (2) albuminuria may exist without casts ; (3) there may be casts in the urine without albuminuria ; (4) casts may be seen in the collecting tubes of a different colour, and of such a calibre that they could not pass through Henle's loops. The local origin of casts in the tubules has been un- doubtedly shown in the cholera kidney and in that of scarlatinal nephritis. * Vide Author's ' Lectures on Bright's Disease,' p. 62. t Ceutralh. f. inn. Med., May 12th, 1894. CHAPTEK V. ABNORMAL CONSTITUENTS OF THE URINE — Continued. Inorganic Substances. Compounds of ammonia are of frequent occurrence in the urine, and the carbonate of ammonia which, in the majority of instances, communicates its alkaline reaction to the urine, arises from the decomposition of urea, either before or after the emission of the urine. Carbonate of Ammonia arises from the decomposition of urea under the influence of a special ferment. This decomposi- tion takes place very rapidly in the presence of pus, or mucus, and especially when the temperature is elevated. Hence it is of frequent occurrence in cases of vesical catarrh. Ammonio-Phosphate of Magnesia. — The formation of this compound is consecutive to that of the carbonate of ammonia. It forms in the bladder, and constitutes a form of gravel. Phosphate of Soda and Ammonia. — In normal urine there exists a neutral phosphate of soda primarily ; and in consequence of the presence of uric acid this salt is transformed into acid phosphate. When ammonia forms through the decomposition of urea, the acid phosphate absorbs it and' transforms it into a double phosphate of soda and ammonia (NaNH 4 P0 4 ). Acid Urat9 of Ammonia (C 5 H 3 (NH 4 ) N 4 0 3 ) is found invari- ably in urine which has become ammoniacal. This urate is not very soluble. On incineration it leaves no residue, and in order to distinguish it from uric acid the ammonia must be separated by treating with soda. It occurs under the form of more or less voluminous spheres, which often present longish spines. Urates 202 THE URINE IN HEALTH AND DISEASE. of lime and magnesia are also found, but more rarely, in the urine. Analysis of Ammonia Salts. — Ammonia salts as existing in the urine are of two varieties, the one volatile at the ordinary boiling-point, the carbonate of ammonia ; the other only decom- posable at a more elevated temperature, and not evolving am- monia except through the agency of fixed alkalies. The following is the process of Schloesing, modified by St. Claire Deville : Put . a known quantity of urine, 50 to 100 grammes, for example, into a small capsule, suspended over a measured quantity of sulphuric acid, in a crystallizer whose base is immersed in mercury. The jar is closed by a plug, perforated by two tubes, the one curved, and closed by a stop-cock ; the other a pipette, also closed by a stop-cock. The pipette is filled with milk of lime in graduated quantity. The stop-cock of the smaller tube is now opened, and a little air is admitted into the jar. The stop -cock of the pipette is now opened, and a little of the milk of lime is permitted to fall into the urine. In about forty- eight hours all the ammonia is evolved, and is absorbed by the sulphuric acid. An alkalimetric analysis will now show the quantity of ammonia evolved. Forty-nine grammes of the standard acid correspond to 17 grammes of ammonia ; it is thus easy to calculate how much ammonia is represented by 10 c.c. of the standard acid. By means of caustic soda the amount of sulphuric acid remaining free may be determined. The dif- ference represents the quantity of acid saturated by the ammonia of the urine, and consequently its proportion. A more rapid process, and one sufficiently exact, consists in the decomposition of the ammonia salts by the hypobromite or hypochlorite of soda. For this purpose the uro-azetometer of Gautrelet-Vieilard may be employed. Sutton recommends the following process : 100 c.c. urine are exactly neutralized with decinormal (^y) soda or potash, as for the estimation of free acid ; it is then put into a flask capable of holding five or six times the quantity, 10 c.c. of normal alkali added, and the whole brought to boiling, taking care that the bladders of froth which at first form do not boil over. After a few minutes these subside, and the boiling proceeds quietly. When all ammoniacal fumes are ABNORMAL CONSTITUENTS OF THE URINE. 203 dissipated, the lamp is removed, and the flask allowed to cool slightly ; the contents are then emptied into a tall beaker, and normal acid delivered from the burette with constant stirring, until a fine glass rod or small feather dipped in the mixture, and brought in contact with violet litmus-paper, produces neither a blue nor a red spot. The number of c.c. of normal acid is deducted from the 10 c.c. of alkali, and the rest calculated as ammonia; 1 c.c. of alkali = 0-017 gramme of ammonia. Example : 100 c.c. of urine were taken, and required 7 c.c. of t n q alkali to saturate its free acid; 10 c.c. of normal alkali were then added, and the mixture boiled until a piece of moistened red litmus-paper was not turned blue when held in the steam ; 4*5 c.c. of normal acid were afterwards required to saturate the free alkali; the quantity of ammonia was, therefore, equal to 5*5 c.c, which, multiplied by 0*017, gave 0*0935 gramme in 1,000 of urine. Sulphuretted Hydrogen.— The urine may contain sulphu- retted hydrogen after the inspiration of this gas or after the ingestion of sulphur. Its presence is demonstrated by acetate of lead. Organized Substances. Blood Corpuscles (H^moglobine). Blood elements are found in the urine under two forms : (a) As Hematuria, in which the urine contains blood cor- puscles, which impart to it an intensity of colour corresponding to their quantity. (b) As Hemoglobinuria, in which the urine contains the colouring principle of the blood, and few or no blood corpuscles. Hematuria. — In this case the urine is of the colour of blood, or of a light brownish colour. It is opaque, and on standing deposits a grayish-red or grayish-brown sediment. Heller's Reaction. — To a few c.c. of urine containing blood, add a little caustic soda, so as to render the liquid strongly alkaline. Heat to boiling. If blood be present, a bottle-green colour results, and the phosphates are precipitated in fine flakes containing the colouring matter of the blood, of a brownish-red colour. 204 THE UBINE IN HEALTH AND DISEASE. Guaiacum Reaction. — Mix carefully 1 c.c. of tincture of guaiacum with an equal quantity of oxidized turpentine (' Sanitas'). Drop gently from a tube along the wall of the vessel containing the urine. A part of the resin of the guaiacum separates rapidly under the form of a whitish precipitate, which becomes of a greenish colour ; but if the urine contains the smallest trace of blood there forms below the resin an indigo- blue coloured zone, which on agitation gives a clear blue emulsion. Or add a few drops of tincture of guaiacum to the urine, and then an excess of ozonic ether — that is, a mixture of peroxide of hydrogen and ether. Shake the mixture : the ether separates, and if blood be present, a fine sapphire - blue colour results. As other substances besides haemoglobine reduce the guaiacum, this test can be regarded only as corroborative. Hseniin Reaction.— For this reaction the coagulum which is deposited from the urine is to be gently heated to dryness with a fragment of chloride of sodium. Treat the mixture with two or three drops of glacial acetic acid. Heat on a glass slide. On cooling, characteristic crystals of hae- min are found. These are small rhomboidal tablets of a reddish-brown colour. Lechine's Reaction. —Add one drop of acetic acid to 10 c.c. Fig. 49.- -Crystals of Haemo- globine. Fig. 50. — Crystals of Hkiwin. PLATE II. 4 Fig. 1. — Red Blood- Globules presenting different Degrees of Alteration. Fig. 2. — Red Blood-Globules presenting a rarer Form of Alteration, highly magnified. Fig. 3. — Leucocytes — Granular and Granulo-Fatty Changes. Fig. 4. — Mucous Cast with altered White Globules. Fig. 5. — Lining of Straight Tube, almost normal. [To face page 205. ABNORMAL CONSTITUENTS OF THE UEINE. 205 of urine, and agitate with 3 c.c. of chloroform. After a few minutes' repose the chloroform becomes red, if the urine contain the colouring-matter of the blood.* Fig. 51. —Red Blood Globules. 'decolorized in the Urine, with Double Contour. Microscopic Examination shows the blood-globules under the form of small discoidal corpuscles of a yellowish colour, slightly biconcave, with well-defined borders. In urine which has become alkaline, however, and in which the corpuscles have lain for a considerable time, the globules become swollen, and present serrated edges. Sometimes they present a double contour, and then become discoloured by the solution of the haemoglobine in the alkali. Hemorrhagic cylinders are frequently met with in the urine, and possess an important diagnostic significance in relation to renal haemorrhage. Rarely crystals of haematoidine are found in the urine. Pathological Significance. — To determine whether the blood be from the bladder or kidney, several points have to be considered. When at the commencement of micturition the urine does not contain blood, or only a minute quantity, and the maximum of blood colour appears in the last drops of urine ; when the colour of the urine is reddish, the reaction alkaline (ammoniacal), and the proportion of albumen is rela- * Pharm. Zeitung, 1887. 206) THE UBINE IN HEALTH AND DISEASE. tively feeble, there is reason to suppose that the haemorrhage is of vesical origin. Even isolated, each of these symptoms would point to this conclusion. Renal Haemorrhage, apart from traumatic lesions and cancer, is usually moderate. The colour of the urine is grayish-brown or reddish-brown. The mixture of the blood with the urine is intimate, the reaction is acid, and the amount of albumen relatively abundant. Elongated or vermiform coagula of from 5 to 10 c.c. in length frequently form in the ureters. They are whitish in appearance, sometimes of the size of a quill. They are most frequently found in cases of renal haemorrhage. Hemorrhagic cylinders can form only in the kidney. Spectrum Analysis. — Oxyhaemoglobine presents two well- marked absorption bands between the D and E Frauhenhofer lines (in the yellow and green). Methaemoglobine, a modifica- tion of haemoglobine containing as much oxygen as oxyhaemo- globine, presents a characteristic ray in the red. According to Hoppe-Seyler, urine in the fresh state never, or only very A 1 1 111 B 111 RED 0RANGJE YELLOW G REEN BLUE VIOL ET! C i Fig. 54.— (a) Spectrum of Haemoglobine ; (b) Spectrum of K educed Haemoglobine ; (c) Spectrum of Urobiline. exceptionally, contains oxyhaemoglobine, but always methaemo- globine. Putrefaction reduces methaemoglobine to haemoglobine, which by agitation with air produces oxyhaemoglobine. Fresh ABNORMAL CONSTITUENTS OF THE URINE. 207 urines, then, give the spectrum of methsemoglobine ; if long kept, the spectrum of haemoglobine or oxyhgemoglobine. Hemoglobinuria. — Hemoglobinuria is symptomatic of exan thematous fevers, certain cases of poisoning, and nervous maladies, etc. The colour of the urine varies from ruby red to black. In t}^pical cases the urine is clear, transparent, and approaches the colour of port-wine. Notwithstanding that chemical tests demonstrate the presence of the colouring matter of the blood, microscopic examination does not reveal blood Fig. 55.— The Spectroscope. corpuscles. Frequently hyaline and granular casts are found, with a brownish detritus. From the chemical point of view the reactions of such urine are simply those of a solution of haem o- globine. Heated to boiling, an albumen coagulum results, but this albumen is not coagulated as ordinary serum albumen in flakes which settle, but immediately forms a brownish coherent coagulum, which floats upon the surface, and can be lifted there- from, and decolorized with boiling alcohol and sulphuric acid. Leucocytes (Pus). Pus is found in the urine in cases of inflammation of some portion of the genito-urinary tract. When the amount is con- 208 THE UBINE IN HEALTH AND DISEASE. siderable, and the evacuation is accomplished in a brief space of time, the existence of an abscess may be inferred, either in the kidney or in the cellular tissue of some of the organs adjacent to the pelvis. In the female the urine may contain pus from the vagina or uterus. Urine containing pus is usually of a pale, grayish yellow, dirty colour. It presents a more or less con- siderable grayish sediment, which on microscopical examination is found to consist of or 7 /^x ^-^ pus-cells, or leucocytes. tents. These granulations conceal the nucleus of the pus-cell (one or two). The addition of acetic acid dissolves the granulations, and the nuclei become apparent. Like the blood, pus is formed of two parts — one liquid, or plasma ; the other solid, composed of the opaque whitish globules just mentioned. The plasma of pus may be separated by nitration. It is an amber-coloured, clear, alkaline liquid, coagulable by heat. It contains the following albuminoid compounds, viz., globulin c, serine, my o sine, and jpyine. The last is precipitated by acetic acid as mucine is ; but the precipitate is soluble in water, a circumstance which dis- tinguishes it from mucine. Purulent urine is most frequently ammoniacal, and its sediment forms a viscous filamentous mass. Sometimes it is entirely transparent, and then all its parts adhere so intimately that it may be emptied from the con- taining vessel as a coherent gelatinous mass. Sometimes, under the action of carbonate of ammonia, the cells undergo certain important modifications. They become clear, their contour fades, and the nuclei are distinguished with difficulty. In such speci- mens of urine there are usually found numerous crystals of ammonio-phosphate of magnesia (triple phosphate) and of urate of ammonia. If a concentrated solution of potash be added to These cells are round, often of crenated outline, have the same appear- ance as mucus-cells, are about twice the size of the red globules of the blood, and are entirely filled with granular con- Fig. 56. — Pus Cells. (a) Normal ; (b) Acted on by Acetic Acid. PLATE III. G 1 Fig. 1. — Overlapping Epithelial Cells from the Vagina. Fig. 2. — Vaginal Epithelial Cell with folded Edges. Fig. 3. — Altered Vaginal Cell (the Nucleus deformed). Figs. 4 and 5. — Normal Bladder Cells of the Rabbit (Super- ficial Layer). Fig. 6. — Normal Cell from Rabbit, Middle Layer. Fig. 7. —Bladder Epithelial Cells as appearing in Urine after^Twenty-four Hours. [To face page 209. ABNORMAL CONSTITUENTS OF THE URINE. 209 urine containing pus, a gelatinous coagulum results ; while in the case of mucus it is liquefied and dissolved under like cir- cumstances. In certain cases of gonorrhoea pus filaments may be found. Urine containing pus is necessarily coagulated by heat, and by filtration the pus globules and the albumen may be separated. Sediments of earthy phosphates which present a certain similarity to pus may be distinguished from it by their solubility in acetic acid. Day's Test for Pus. — The late Dr. Day, of Geelong, recom- mended the following test for pus. To the purulent urine add a drop or two of tincture of guaiacum, when a clear blue colour is produced. If the pus be dry, before applying this test it is necessary to moisten it with water. Eecently oxygenated water has been recommended as a test. It determines an effervescence due to oxygenation. Mucus. The appearance of mucus is usually characteristic. It forms a flocculent, cloudy, semi-transparent deposit of feeble coherency. Owing to its feeble density, it remains long sus- pended in the urine. It becomes fluid on the addition of ammonia, whereas pus becomes gelatinous. Urine containing mucus does not necessarily give an albumen precipitate. Day's test for mucus consists in the application, first, of oxidized tincture of guaiacum, which alone undergoes no change in con- tact with mucus, but on the addition of carbolic acid or creosote the colour of the guaiacum becomes bright blue. On micro- scopic examination mucus is found to consist principally of filaments, made more manifest by the addition of acetic acid, and some clear, round cells. Whenever the addition of acetic acid to urine causes a slight cloudiness, the urine contains mucus. If microscopic examination reveals leucocytes, and if albumen exist, there is muco-pus in the urine. Epithelial Cells. In the cloudy deposit which forms in normal urine most frequently exist epithelial cells from the bladder. The des- quamation of epithelium may take place from the kidney to the urethra, and the origin of the cells is determined by their special 14 210 THE UKINE IN HEALTH AND DISEASE. character. The epithelial covering of the genito-urinary tract comprises three layers : the superior layer, formed of large rounded or polygonal scales, with a nucleus ; the middle layer, composed of spindle cells, whose tapered extremity is insinuated into the inferior layer ; and the innermost layer, composed, of ovoid elongated cells, smaller than those of the surface. Des- quamation of the superficial cells is constantly taking place. The epithelial cells most frequently found are those of the bladder. They appear as transparent rectangular plaques, with rounded or elliptic angles, with a nucleus with a border more defined than that of the cells of the vagina. They are isolated, or aggregated together in plaques, of greater or less size. By their borders they are in apposition to one another, and some- times they are slightly imbricated. These cells are found in the urine of females as well as of men. In the former case vaginal epithelium may be found. These are abundant when the vagina is the seat of inflammation. They are of the same form as the cells of the bladder, but are larger, with thinner edges and a smaller central nucleus. These cells resemble those of the inferior portion of the ureter and prepuce. The cells of the neck of the bladder are caudate. They pro- bably represent the middle layer of the epithelial covering. The cells of the ureters and pelvis of the kidney are smaller than the preceding, and are club-form, having a nucleus in the head, or enlarged portion. The epithelium of the ureter is stratified pavement. The cells are long and cylindrical. They are granular, and above the oval nucleus there is found one, rarely two, brilliant drops, which resist the action of acetic acid. The cells which come from the pelvis of the kidney are fre- quently small, round, or oval, with large nuclei, and are generally united in plaques. This grouping is very significant, for if along with it there is acidity of the urine, we have here a pathog- nomonic distinction between pyelitis and cystitis. Kenal epithelium is formed of round or polyhedral cells, generally isolated, and with a granular or clear protoplasm, granular in the cells of the tubuli contorti, clear in those of the descending branch of the loop of Henle. The nucleus is large and distinct. PLATE IV. Fig. 1. — Cells from the Straight Tubes. Fig. 2. — Fatty Debris, without Nucleus, from the Convoluted Tubes. Fig. 3. — Irregular Fatty Mass from the same region. Fig. 4.— Overlapping Epithelial Cells from the Vagina. Fig. 5. — Normal Cells from Middle Layer of the Bladder. Fig. 6.— Nucleated Fatty Mass from the Convoluted Tubes. Fig. 7. — Normal Cells from the Deep Layer of the Bladder and Ureter. [To face page 210. ABNORMAL CONSTITUENTS OF THE URINE. 211 These cells undergo great modifications as the result of patho- logical processes. Thus, in cases of fatty degeneration of the kidney they contain small refractive fatty granulations, and their volume is much augmented. They are easily recognised. When they are found on tube-casts, or when united with other elements, they constitute epithelial casts. The epithelial cells of the urethra are elongated, cylindrical, and slender inferiorly. They are granular, and possess an oval nucleus. The presence of epithelial cells in the urine is of no patho- logical importance when in small quantity. If abundant, they indicate a corresponding amount of desquamation, and conse- quently inflammation of some portion of the genito-urinary tract. The form of the cell may indicate the seat of the disease. Abundant desquamation is almost invariably associated with the formation of pus, and leucocytes and albumen are then found in the urine. This applies more especially to cystitis, for in nephritis tube-casts take the place of epithelial cells. Spermatozoa. Spermatozoa are found in the urine after coitus, after involun- tary seminal emission ; usually in cases of spermatorrhoea ; after epileptic attacks ; may be passed from the urethra at stool, especially when the bowels are constipated, and when the prostatic ducts are relaxed and atonic ; in cases of chronic prostatitis, and during the course of several constitu- tional diseases, such as typhoid fever, and after apoplectic and epileptic attacks.* Like pus, the semen is composed of a fluid and a solid portion. Urine con- taining semen is not usually markedly cloudy. The liquid portion contains an albuminous principle, sjpermatine, which Fig. 57. — {a) [b) Spek- is precipitated by acetic acid, and matozoa laegely Mag- soluble in an excess, by which it is differentiated from mucine. Allowed to stand, however, for * Vide ' Prostatorrhoea/ by Author (Lancet, October, 1882), and ' The Functional Diseases of the Urinary and Reproductive Organs,' second edition (Churchills, London). 212 THE URINE IN HEALTH AND DISEASE. some time in a conical glass, the semen deposits in from six to eight hours, when it may be examined microscopically, and the characteristic appearance of the spermatozoa be demon- strated. Spermatozoa resemble the tadpole in form, com- posed as they are of a head, which is ovoid or triangular, and a long filiform tail. In semen recently ejaculated the spermatozoa exhibit great activity. Sometimes spermatozoa Fig. 58.— Spermatozoa, with Fig. 59. — Spermatozoa, Blad- Acid Urate of Ammonia, Blad- der Epithelium, and Prostatic der Epithelium, and fragments Casts (passed from Urethra at of Prostatic Casts (passed at stool), stool). are found in fragments in the urine, the tail especially being broken ; notwithstanding this, the head can be easily recognised. In the case of copious seminal losses, besides the spermatozoa, certain particles like sago grains (corpuscles of Lallemand- Trousseau) are found in the urine. According to Furbringer, they are composed of a substance analogous to globuline, and come from the seminal vesicles. In the absence of spermatozoa these bodies do not possess any diagnostic significance. If semen be allowed to dry on a glass slide, prismatic or pyramidal colourless or yellow crystals, grouped in a stellar form, are observed (crystals of Bottcher). According to Schreiner, these PLATE V. Fig. 1. — Gonococcus enlarged about 200 Diameters. Fig. 2. — Gonococci in Pus Cells, (d) Pus cell, (p) Cell proto- plasm contracted by alcohol, (y) Gonococci (12 immer. objective). Fig. 3. — Isolated Gonococci in Epithelial Cells, {a) Cell containing at each extremity a mass of gonococci. {b) A mass of gonococci upon an epithelial cell, (c) Cell with a few gonococci. {d) Gonococci outside the cell. [To face page 213. ABNORMAL CONSTITUENTS OF THE URINE. 213 crystals are a combination of phosphoric acid with an organic substance. Spermatic sediments frequently contain crystals of oxalate of lime, especially in cases of spermatorrhoea, leucocytes, epithelial cells, granules of urates, crystals of uric acid and of triple phosphate. Organisms found in Urine. The parasitic animal most frequently found in the urine, in Europe, is Echinococcus hominis. It is either found in sus- pension in the urine or in its sediments. It is easily distin- guished by its hooklets and stratified membranous scales. In hot countries, and notably in Egypt and South Africa, the urine is often found to contain the egg and ciliated embryos of the Distoma hcematobium or Bilharzia hcematobia. This worm is also found in the vena per tee and its branches, as well as in the venous plexus of the bladder. The eggs are deposited in great number by the female in the interior of the vessels, and within the vesical mucous membrane, and ultimately perforate the membrane, hematuria being the result. In this case the urine is bloody, and deposits a reddish flocculent sediment, containing blood-crystals, leucocytes, and eggs of the Distoma. In the East Indies there is found in the urine and in the b^ood of persons suffering from chyluria, embryos of the Filaria sanguinis hominis, which have also been observed by Bresil in endemic hematuria, this affection being due to their existence in the blood. Almost invariably chyluria is accompanied by haematuria (hsemato-chyluria). The so-called bacillus of tuberculosis is stated to be found in the urine of persons suffering from phthisis. It is thus held to constitute a valuable differentiating feature between typhoid fever and miliary tuberculosis of the genito- urinary system. Sometimes there is accidentally found in the urine Trichomonas vaginalis, a parasite living in the vaginal mucus ; the Bodo or Cercomonas urinarius described by Hassal in alkaline urine ; the Oxyuris vermicularis , whose habitat is the inferior portion of the intestine ; the Strongylus gig as from the kidney ; the Ascaridis lumbricoides and its eggs, passing through an abnormal communication from the intestine 214 THE UKINE IN HEALTH AND DISEASE. to the bladder. Of Saccharomycetes, the Saccharomyces urince, which is probably identical with the yeast fungus, Saccharo- myces cerevisice, has been found in diabetic urine. These cells are ovoid, and brilliant, and of about the size of a red blood- corpuscle. Sarcinoz may also be found in the urine, indepen- dently of their existence in the stomach. According to Pasteur, Tieghem, and Miguel, the Micrococcus and Bacillus urinai, which are the cause of the decomposition of urea, may also be found in the urine. In acute infectious maladies, such as diphtheria, typhoid fever, scarlet-fever, small-pox, etc., a large quantity of bacteria are often found in the urine, almost invariably with the presence of albumen. In cases of gonorrhoea the Gonococcus of Ncisser often exists in the urine. This element is by no means pathog- nomonic of gonorrhoea, as many cases of gonorrhoea have been observed where it was absent. This microphyte is found in the purulent deposit in the form of small round or oval grains, most frequently aggregated in groups. They are readily stained with methylene blue and fuchsine. PLATE VI. Fig. 1. — Bilharzia H^ematobia. The inferior extremity of the female protrudes from the gynsecophoric canal of the male. (6, c, d) Male, (a) Mouth-sucker. (e,f) Female in part free. Fig. 2. — Two Eggs of Bilharzia ILematobia. (a) With large segmentation of the vitellus. (b) With vitelline granulations. Fig. 3.— (a, b, c) Embryos of rilaria. {a) Head. (6) Tail, (e) Body (d) Egg containing an embryo, (e) Egg showing vitelline segmen- tation. [ To face page 214. PLATE VII. Fiji Kf 2 Fig. 1. — Sarcin^ Urin^e. (a) Group of sixteen, (b) Group of four. Fig. 2. — Micrococcus Ure,e. Fig. 3. — Ferment of Saccharine Urine, (a) Cells in opposi- sition to each other. Fig. 4. — Penicillium. (s) Spore in mycellium tube. Fig. 5. — Mass of Micrococci in Albuminous Urine. Fig. 6. — Yeast Cells. Fig. 7. — Vibrios. Fig. 8. — Bacilli, (a) Isolated bacillus. (b) Bacilli joined to- gether, (c) Chain of bacilli. Fig. 9. — Yeast Cells, {a) Oval cells. (6) Cells joined together, (c) Bacteria. [To follow Plate VI. CHAPTEK VI. SEDIMENTS. Under ordinary conditions the normal and pathological elements which have engaged attention in the foregoing pages are found in a state of solution in the urine. When, however, there happens to be either relatively or absolutely an augmentation of those constituents in the urine, they may, in consequence, undergo precipitation, either in the urinary passages or in the urine after it is voided from the bladder and has become cold. In the former case the urine is more or less milky when passed, while in the latter it is limpid and transparent. In other cases the urinary sediment is due to hyperacidity of the urine, or, on the contrary, to an absence of the normal acidity. There are certain urinary constituents which continue in solution in normally acid urine, but which undergo precipitation when the urine becomes either preternaturally acid or unduly alkaline, and this change may take place either before or after the emission of the urine. Sometimes new insoluble combinations are formed. Sediments may thus be composed of bodies which on account of their insolubility are only found in suspension in the urine, these constituents being always of an organized pathological nature, and designated organized sediments, in contradistinction to the non-organized sediments, which may be composed either of mineral or organic substances. Sediments may thus be frequently a combination of non- organized mineral bodies or of organized organic elements. When the sediments form in the urinary passages, and are detained there, they may become concretions of more or less 216 THE URINE IN HEALTH AND DISEASE. size. In small form they may be expelled with the urine as gravel ; in larger size they may become renal or vesical calculi. Examination of Sediments. — In order to determine the nature of urinary sediments, both microscopic and chemical examination are most frequently required. As a preliminary step, however, the sediment must be isolated. In order to accomplish this, the urine is decanted into a conical glass, and allowed to stand undisturbed until a deposit takes place. The clear, supernatant fluid is then poured off carefully, and a pipette introduced into the remaining portion. Holding the pipette in a vertical position, the deposit accumulates in its narrower portion, and it can now be transferred to an object- glass. Microscopic examination can then be made with a power varying from 200 to 400 diameters. A chemical examination may be made by allowing a drop or two of the reagent to penetrate between the slide and the cover-glass. Non-Organized Sediments. — The non-organized sediments most frequently met with are uric acid and urates, oxalate of lime and earthy phosphates (phosphate of lime and triple phosphate) ; and more rarely xanthine, hippuric acid, tyrosine, bilirubine, indigotine, haematoidine, and carbonate and sulphate of lime. Distinctive Characters. — The following table exhibits the differentiating features of the sediments of this group : I. The Urine has an Acid Keaction. A. The Sediment is Amorphous, 1. It is composed of small granules which dissolve on heating ; acetic acid dissolves them, and after some hours small rhomboidal tables of uric acid separate (crystals of uric acid and of oxalate of lime may also be contained in the sediment). The sediment is composed of urates (vide pp. 74 and 75). 2. The sediment presents the appearance of dumb-bell crystals , and is insoluble in concentrated acetic acid, but soluble in hydro- chloric acid without separation of crystals. The sediment consists of oxalate of lime (vide pp. 93 and 94). 3. The sediment is insoluble in acetic acid and concentrated hydrochloric acid. It consists of sulphate of lime. SEDIMENTS. 217 4. The sediment consists of round, refractive bodies of a pearly colour. It consists of fat (vide p. 195). 5. The sediment consists of yellow granular masses. It consists of bilirubine (vide p. 224). B. The Sediment is Crystalline. 1. Yellow or brown crystals of rhomboidal form, isolated or grouped in diverse manners, alone or accompanied with urates and oxalate of lime, soluble in soda ; and the addition of concen- trated hydrochloric acid gives after the lapse of a few hours small yellow rhomboidal plates. Uric acid, (vide p. 70). 2. Colourless octahedral crystals, yellow in the ' case of urine containing bile, transparent, very refractive, envelope form, sometimes of quadrangular prismatic forms, terminated by pyramids, insoluble in acetic acid, but soluble in hydrochloric acid. Oxalate of lime (vide p. 93). 3. Large crystals of the coffin-lid shape, in urine faintly acid, in appearance somewhat similar to oxalate of lime crystals, but soluble in acetic acid. Triple phosphates (vide pp. 222, 223). 4. Small tubular crystals, regular and six sided, insolmVe in acetic acid, but soluble in ammonia. Cystine (vide pp. 108 and 109). 5. Colourless needle-shaped crystals, insoluble in acetic acid and soluble in ammonia. The addition of hydrochloric acid causes the deposition of small hexagonal plates. Xanthine (vide p. 224). 6. Large rhombic crystals, strongly refractive, elongated, and very fine. Their angles are rendered opaque and de- stroyed by carbonate of ammonia ; frequently found in alkaline urine. Basic phosphate of magnesia (vide p. 114). 7. Isolated or grouped prisms, (a) Soluble in ammonia. Hippuric acid (vide p. 83). (b) Insoluble in ammonia and acids. Sulphate of lime. 218 THE URINE IN HEALTH AND DISEASE. 8. Cuneiform prisms terminating in points, isolated or grouped together in stellar form ; soluble in acetic acid and segregating in ammonia. Neutral phosphate of lime. 9. Tufts of fine needle-like crystals, insoluble in acetic acid, and soluble in ammonia and hydrochloric acid. Tyrosine {vide p. 224). 10. Small rhomboidal tables of a yellow colour, and accom- panied by amorphous granular masses of a similar colour, soluble in soda ; and on contact with acetic acid they surround themselves with a multicoloured areola, in which a green zone is observed. Bilirubine (vide p. 224). 11. Needle-formed crystals, sometimes rhombic, and yellow or brownish-yellow, becoming blue in contact with nitric acid. Hcematoidine. II. The Urine has an Alkaline Reaction. If the urine becomes alkaline only after emission, it may con- tain such sediments as uric acid, oxalate of lime, sulphate of lime, etc. If the urine, on the other hand, is eliminated with an alkaline reaction, or if it deposits a sediment while it is becoming alkaline, the following sediments may be found : A. The Sediment is Amorphous. 1. It is composed of small granules soluble in acetic acid : (a) Without evolving gases — Earthy phosphates. b) Evolving bubbles of gas — Carbonate of lime. 2. Masses in form of dumb-bells, soluble in acetic acid, with disengagement of gas bubbles. Carbonate of lime. 3. Spheroidal masses of a dark colour, with crystalline points, soluble in hydrochloric and acetic acids, with subsequent deposition of rhomboidal tables of uric acid. Urate of ammonia (vide p. 75). B. The Sediment is Crystalline. 1. Large colourless prisms of coffin-lid shape, very soluble in acetic acid. Ammonio- phosphate of magnesia (vide p. 109). SEDIMENTS. 219 2. Masses of blue needle-formed crystals, and small tabular blue crystals. Uroglaucine or indigotine. Uric Acid and Urates. — Sediments of urates are most fre- quently observed in acute febrile affections, such as in acute rheumatism, pneumonia, etc., or during exacerbations of chronic affections, especially in disorders of the digestive apparatus, such as dyspepsia and chronic gastric catarrh ; and in affections of the respiratory passages, such as dyspnoea, asthma, pulmonary emphysema, etc. The formation of urates in the urine is not always necessarily due to the excess of uric acid in the urine. In cases of rheumatism, for example, urates are found in abund- ance in the urine, while the amount of uric acid is usually normal. It is to the presence of acid phosphates in the urine that the precipitation of urates is most frequently to be ascribed, the neutral urates being thus transformed into acid salts, which are much less soluble ; or otherwise, the volume of urine elimi- nated being diminished, there is not a sufficiency of water to hold the urates in solution. Cooling of the urine also causes a precipitation of the urates, as they are much more soluble in hot than in cold solutions. Hence deposits of urates may be found in the urine of perfectly healthy individuals, especially after violent physical exertion, large ingestion of food, after abundant sweatings, and during winter, the urine being exposed to a low temperature. . Cylindrical masses composed of urates are not infrequently observed in the urine of infants, these being of a brown or reddish colour, and originating in the renal tubes. The decomposition of neutral urates by acid phosphates, during the earlier stages of the decomposition of urine, causes a deposition of acid urates and uric acid {vide p. 220). Sediments of free uric acid are of rarer occurrence. They are sometimes found alone, at other times accompanied by urates. In the former instance they are expelled with the urine in the form of uric acid gravel, in which case they originate in the urinary passages. Characters of Urates. — Deposits of urates, as we have already seen, are of yellow or brick-red colour, according as urinary or hepatic pigments predominate. They usually consist of a mixture 220 THE URINE IN HEALTH AND DISEASE. of various urates, most frequently of potassium and sodium, sometimes urate of ammonia, and more rarely of urate of lime Fig. 60. — Uric Acid. Fig. 61.— Uric Acid. and magnesia. Deposits of urates are not infrequently combined with free uric acid and oxalate of lime. Examined microscopically, these deposits present the appear- ance of fine amorphous granulations irregularly grouped, and of Fig. 62.— Urate of Sodium. Fig. 63.— Urate of Ammonia. easy solubility by heating, precipitating again when cooling takes place. Should the proportion of urates be so considerable as to SEDIMENTS. 221 render obscure the presence of other sediments, such as uric acid and oxalate of lime, separation may be effected by filtering the heated urine : the urates will pass through, and the uric acid and the oxalate of lime will remain on the filter. Treated with hydrochloric acid, deposit of urates yields uric acid. Urate of Ammonia.— This urate is most fre- quently found in alkaline urine, in combination with earthy phosphates, and in the form of fine granu- lations. Uric Acid Sediments present the form and characteristics already de- scribed (vide p. 70). Hippuric Acid. — Sedi- ments of hippuric acid are rare (vide, p. 83 et seq.). Hippuric acid crystals resemble in appearance certain forms of uric acid and of triple -phosphate. They are distinguished from the former by not giving the murexide re- action, and from the latter by their insolubility in hydrochloric acid. Oxalate of Lime. — Occasionally, in perfect health, oxalate of lime may be found in the urine. It may exist as a sediment, or be suspended in the mucus of the urine. It exists in considerable abundance in the urine in certain diseases, in connection with the oxalic acid diathesis, and after the ingestion of certain vegetables. Fig. 64. — Hippuric Acid. (a) Rhombic prisms ; (b) needle form. Oxalate of Lime. 222 THE URINE IN HEALTH AND DISEASE. Oxalate of lime precipitates from the urine simultaneously with acid urates and uric acid. Sometimes the crys- tals of oxalate of lime resemble certain forms of chloride of sodium and triple phosphate. From the former they are distinguished by their insolubility in water, and from the latter by their insolu- bilit} 7 in acetic acid. Earthy Phosphates. — Sediments of earthy phosphates are usually Fig. 66. — Triple Phosphates (Phos- found in chronic dis- phates of Ammonia and Magnesia). eases, such as phthisis, rickets, mollities ossium, etc. These phosphates are deposited from the urine in consequence of its becoming neutral or alkaline, and being thus incapable of holding the earthy phos- phates in solution. If the urine contain a sedi- ment of earthy phos- phates when voided, it is evident that the sedi- ment forms within the bladder, and is probabty associated with some inflammatory condition of the genito- urinary tract. Long persistence of earthy phosphates in the urine would pro- bably indicate vesical Fig. 67.— Triple Phosphates calculi. (Feathery Form ). Characters of Earthy Phosphates.— The triple-phosphate presents the above appearance (Fig. 66). The crystals are of considerable size, and SEDIMENTS. 223 are very soluble in acetic acid. When the deposition of earthy phosphates is the result of rapid evaporation, the crystals present the " feathery" form (Fig. 67). Phosphates of lime and magnesia deposit from urine which has become alkaline, or is voided as such. They present the form of amorphous, trans- parent, and rounded plaques, distinguishable from urates in not being dissolved by heating. These phosphates may exist alone, or be com- bined with ammonio- phosphate of magnesia. The deposit may be so thick as to be mistaken for pus. Phosphate of Lime Stellar Phosphates of Lime. Fig. 68. is found in the urine in the form of prismatic crystals, colour- less, and isolated or in tufts. It is distinguished from uric acid by its solubility in acetic acid. Phosphate of magnesia is sometimes found in neutral or con- centrated alkaline urines in the form of fine refractive rhom- boids. When the urine is not coloured by pigments to an ab- normal extent, the deposits of earthy phosphates present a white appearance. They are insoluble in water and in alkalies, but dissolve readily in mineral acids and acetic acid. Carbonate of Lime. — Sometimes crystals of carbonate of lime are found mixed with the earthy phosphate deposits of the dumb-bell variety. They are distinguished from oxalate of lime crystals of like form by their easy solubility in acetic acid. Sulphate of Lime. — In rare instances this salt is found in the urine under the form of colourless elongated needles or tubular crystals, insoluble in ammonia and acetic acid, and sparingly soluble in nitric and hydrochloric acids. Cystine {vide p. 179). — Deposits of cystine are rare in the 224 THE UKINE IN HEALTH AND DISEASE. urine. They may, however, persist a long time in the urine without any evident constitutional derangement. Xanthine. — The presence of xanthine in the urine was first demonstrated by Bence Jones in a case of nephralgia. Xanthine crystals are of two forms (Fig. a, and the form b). The latter are produced when the xanthine is dissolved by heating (thus contra-distinguished from uric acid), treated with hydrochloric acid, and evaporated. These crystals are then deposited. They are soluble in water. Tyrosine. — In cases of yellow atrophy of the liver tyro- sine has been found as a urin- ary sediment. Bilirubine. — In certain cases of jaundice and pyelitis, bilirubine has been found as a urinary deposit. It either presents in an amor- phous form or its character- Fig. 70.— Tyrosine. Fig. 71.— Bilirubine. istic crystalline form. It is of a yellow or brown colour, and is very soluble in alkalies and chloroform. With nitric acid it gives the special bile-pigments' reaction. SEDIMENTS. 225 Uroglaucine, or Indigotine.— In urine containing a large amount of indican, uroglaucine^ or indigotine, may be found as a deposit. It presents under the form of scales or needles of a bluish colour. Haematoidine. — Ebstein and other observers have found haematoidine in certain urinary deposits, especially in cases of pyelitis in pregnancy, in amyloid a degeneration of the kidneys, in Wk S crystals (Fig. 72). These crystals Fig. 72.— Crystals of Hjsma- surface of tube-casts, and bladder and renal epithelium. They are of a yellowish or reddish-brown colour, and are distinguished from bilirubine, with which they are apt to be confounded, by a transient blue colour which contact with nitric acid imparts to them. scarlatinal nephritis, in typhoid fever, in cancer of the kidneys, and cancer of the bladder. Haematoi- dine is the product of decomposi- tion of the blood,' and is found in cases of blood extravasation of long standing. Microscopic exami- nation shows it in the form of acicular, or sometimes rhomboidal, are often found deposited on the TOIDINE. Fig. 73. Cholesterine is sometimes found as a urinary deposit in cases of chyluria and fatty degeneration of the kidneys (vide p. 194). 15 CHAPTEE VII. TO DETERMINE THE CHEMICAL COMPOSITION OF A CALCULUS. Pulverize the calculus, and heat to redness in a platinum crucible. The powder burns completely, and leaves hardly any residue (A). The powder blackens, and leaves a considerable residue (B). A. The calculus is composed entirely of organic substances. The primitive cal- ' cuius is saturated (a) Treated with caustic with nitric acid, and potash, nothing is evolved, after evaporation is-< treated with am- (b) Treated with potash, monia (murexide ammonia is evolved, reaction). V / (a) The nitric solution evaporated gives a yellow residue on cooling, which is coloured by potash (cold) reddish-yellow, and heated, violet-red. (b) The nitric solution" evaporated gives a dark / brown residue ; the powder tion with ammonia, ( ,. , . 9 . r -. . Al • -, dissolves m ammonia and m gives the murexide , , • i 1 rea tion potash ; the ammoniacal solu- tion, acidified by acetic acid, deposits microscopic hexa- gonal tubules ; dissolved in potash,* with the addition of nitro-prussiate of soda, a \ beautiful violet coloration is \produced. The nitric solu- tion, after evapora- Uric acid. Urate of ammonia. -Xanthine. >Cystine. CHEMICAL COMPOSITION OF A CALCULUS. 227 The powder burns with a brilliant flame. Fibrine or blood clot. Bile pig- ments. r (a) It is insoluble in potash.^ Treated with ether it gives a solution which on evaporation rCholesterine. deposits pearly rhomboidal | scales. (b) During the heating it | evolves a burnt-horn odour ; it is insoluble in potash, and j ^precipitable by acetic acid. The powder treated with chloroform gives an orange-yellow colour, and on the addition of nitric acid gives the reaction of Gmelin. B. The primitive poivder, treated with nitric acid and ammonia, gives the murexide reaction ; it contains urates with fixed base (soda, potash, magnesia, lime), oxalate of lime, phosphate of lime, carbonate of lime, ammonio -phosphate of magnesia, (1) The residue is easily disintegrated by the blow-pipe. The primitive powder evolves ammonia on being treated with potash. Calcined alone, it gives off an ammoniacal odour. It dissolves in acetic acid, and ammonia} Ammonio . phos . Hmfform " * ! P hate of ma gnesia. (2) The residue is unaffected by the blow-pipe, (a) The residue is white/ The powder does not effervesce either before or after calcina- tion. It is soluble in hydro- chloric acid, and is precipi- tated from this solution by ammonia. It also dissolves in acetic acid; the acetic solution gives, with oxalate of ammonium, a precipitate of ^oxalate of lime. j (b) The primitive powder \ is unaffected by acetic acid; it is dissolved by mineral acids with effervescence, and is precipitated by ammonia. The alkaline residue effer- vesces with acids. (c) The powder, heated for white heat, develops an in- tense white flame ; before calcination it effervesces with acids. It is precipitated from a neutralized chlorhydric solu- Ition. Non - alkaline residue. Basic phos- phate of lime. Alkaline residue. Oxalate of calcium. Carbonate lime. of 228 THE UEINE IN HEALTH AND DISEASE. (3) The primitive powder gives with nitric acid and ammonia the uric acid reaction, but heated to redness it leaves a residue. Residue fusible by the blow-pipe. Residue non-fus- ible by the blow- pipe. (a) It communicates to the flame an intense yellow colour. (b) It imparts to the flame \ a violet colour, and chloride ( of platinum precipitates it f from a chlorhydric solution. ) f (a) After calcination reactions are those of carbon ate of lime. (b) It dissolves with feeble ^ effervescence on being treated with dilute sulphuric acid, and is precipitated from this solu- tion by phosphate of soda and ammonia. its] on- > Urate of soda. Urate of potassium. Urate of lime. Urate of magnesium. In the case of a mixed calculus, with different layers super- posed on one another, the following process is to be observed : Boil the calculus in a little distilled water ; filter, and separately collect the filtered portion (A) ; wash the residue with boiling water. Boil the washed residue in dilute hydrochloric acid, and if effervescence result, the presence of carbonate of lime is indicated. Then filter the acid liquid. Collect the filtered liquor (B), and wash the residue, if any, with water. Aqueous Solution (A). — The aqueous solution may contain urate of ammonium, urate of sodium, and urate of calcium. Evaporate a few drops of this solution on a watch-glass, and if but a small trace of residue be obtained, allow the remainder to repose, and regard the calculus as containing only an appreciable quantity of alkaline urates. If, on the contrary, an appreciable residue is obtained, boil about a fourth of the solution with a little caustic potash. Should the liquid contain ammonia, this gas is evolved, and may be recognised by its odour and other tests. The remainder of the solution is reduced by evaporation to a small volume, a little concentrated nitric acid is added, and evaporation to dryness is accomplished. A rose-coloured residue becoming red by the addition of ammonia indicates the presence of uric acid. The residue is incinerated and the ash dissolved CHEMICAL COMPOSITION OF A CALCULUS. 229 in water, the liquor being divided into two portions. Acidulate the one portion with acetic acid, and add a drop of oxalate of ammonia, which in presence of calcium produces a white pre- cipitate. The other portion is acidulated with hydrochloric acid and evaporated to dryness. The presence of chloride of sodium is manifested by small cubical crystals. Acid Solution (B).— This solution may contain chloride of sodium arising from the decomposition of carbonate or oxalate of calcium, of cystine, of phosphate of lime, or of ammonio- magnesium-phosphate. Add dilute ammonia so as to render the solution as neutral as possible without affecting its trans- parency, and then a little acetate of ammonium, which causes a white precipitate if the liquor contains oxalate of lime or cystine. The latter is rarely found in mixed calculi, and is easily separated from oxalate of lime by means of ammonia. If the acetate of ammonium precipitates, filter and add an excess of oxalate of ammonium to the filtered liquid; if the acetate of ammonium does not precipitate directly, treat the clear liquid with oxalate of ammonium without previous filtration. The presence of calcium is indicated by a white precipitate. If necessary, then filter and add ammonia in excess. The presence of phosphoric acid and magnesium is indicated by a white precipitate. If no precipitate is produced, add sulphate of magnesia. The presence of phosphoric acid is then indicated by the deposit of a white crystalline powder, after agitation of the liquid. Residue (C.) — This consists of uric acid, recognisable as above. Sand and Gravel are analyzed like calculi. They should previously be submitted to microscopical examination, as they may present physical appearances by which they may be dis- tinguished. CHAPTER VIII. MEDICAMENTS AND ACCIDENTAL ELEMENTS IN THE URINE. Alcohol. Antipyrine. Antifebrine (Acetanilide). Arsenic and Antimony. Alkaloids. Aristol. Bromides. Carbolic Acid. Chloroform. Chloral. Chlorate of Potash. Iron. Iodides. Iodoform. Kairine. Lithia. Lead and Copper. Mercury. Naphthaline. Naphthol and other Phenols. BethoL Phenacetine. Salicylates. Salol. Saccharine. Strontium. Tannin. Turpentine. Rhubarb. Santonine. Thalline. Urethan. Filaments of Tissues ; Grains of Starch. Alcohol. — The greater portion of the alcohol taken into the system is changed by oxidation into carbonic acid and water, and consequently, when imbibed in large quantities, is found only in diminished quantity in the urine. This portion, however, may be separated from the urine by a process of distillation. About 100 c.c. of urine are to be distilled in a glass retort with a refrigerating apparatus. If to a few drops of the product of distillation a few drops of a dilute solution of bichromate of potash and dilute sulphuric are added, and heat applied, if the urine contain alcohol, the original yellow colour passes into green in consequence of the reduction of chromic acid to chromic oxide, while simultaneously an odour of aldehyde is MEDICAMENTS AND ACCIDENTAL ELEMENTS IN URINE. 231 evolved. Otherwise (xanthogen reaction), the product of the distillation of the urine, once or twice rectified, is mixed with a little caustic potash and a few drops of sulphide of carbon ; after agitation, an equal volume of water is to be added, and a drop of sulphate of copper solution. If any alcohol is present, a yellow precipitate of xanthogenate of copper forms. The reaction of Leben may also be applied, as in the case of acetone (vide Acetone). Antipyrine. — The frequent use of antipyrine renders its presence in the urine of clinical significance, and especially in its behaviour towards the usual albumen and sugar reagents. Polarimetric Examination. — Feeble or concentrated solution of antipyrine does not affect the plane of polarization. It is otherwise with the antipyrine which has traversed the economy, and which has doubtless thus undergone some change ; it deviates the plane of polarization to the left. Nitric acid does not affect antipyrine, but Tanret's solution (vide Albumen, p. 126) gives a precipitate readily soluble in alcohol, and on being heated. The precipitate formed with peptones and alkaloids is even more soluble. EsbacJi's reagent likewise precipitates antipyrine. M elm's reagent gives a precipitate of antipyrine very soluble in alcohol, and on application of heat, reappearing when the liquid cools. F err o cyanide of potassium and acetic acid solution is without effect on antipyrine. To be absolutely certain of the presence of albumen, five tests must be applied, thus : Rota- tory Power. Nitric Acid. Tanret's Solution. Esbach's Solution. Menu's Reaction. Ferrocy. Potass, and Acet. Acid. Albumen - Stable Stable Precip. Precip. Precip. precip. precip. stable stable stable Antipyrine 0 Precip. Precip. Precip. 0 soluble soluble soluble («)by («) by («)by heat, heat, heat, (6) by (6) by (b) by alcohol alcohol alcohol Alkaloids 0 0 Do. Do. Do. 0 Peptones - 0 0 Do. Do. Do. 0 232 THE URINE IN HEALTH AND DISEASE. Having separated the albumen by heat, the presence of anti- pyrine may be demonstrated by means of perchloride of iron and Tanret's solution. The action of the perchloride of iron must not be confounded with the violet coloration due to the presence of salicylates in the urine (vide Salicylates, p. 237). Having proved the absence of salicylates, it may be concluded that the red coloration produced by the perchloride is due to antipyrine. In this operation it is indispensable that the urine be not treated with subacetate of lead, as the presence of acetates occasions with the perchloride of iron the same colour as does antipyrine. If the urine be decolorized by a 20 per cent, solution of nitrate of lead, and ferric chloride be added, a precipitate of chloride of lead is obtained. Antipyrine causes a partial decoloration of Fehling's solution, the colour of the reagent passing from yellow to violet-gray. Antipyrine therefore interferes with Fehling's test in the presence of sugar. On treating urine containing antipyrine, and adding a few drops of fuming nitric acid, a green coloration is produced, which becomes red with an excess of the acid. Antifebrine. — The presence of antifebrine is thus revealed : The urine is mixed with a fourth of its volume of concentrated sulphuric acid and boiled for a few minutes. On cooling, a few drops of carbolic acid or hypochlorite of lime are added. If antifebrine be present, the solution becomes red on the addition of nitric acid. Subsequently it becomes of a beautiful blue colour (iodophenol reaction). If the urine be agitated with chloroform, and evaporated, and the residue be heated with nitrate of mercury, a green coloration is the result, in which traces of acetanilide exist. Arsenic and Antimony. — Destroy the organic matters with chlorate of potash and hydrochloric acid. Evaporate until the complete expulsion of the chlorine ; wash the residue with water ; evaporate the filtered liquid to a third of its volume, and test for the metals by Marsh's method. Alkaloids. — The animal alkaloids found in the urine are of two varieties, viz.: (i) The ptomaines, which develop in dead MEDICAMENTS AND ACCIDENTAL ELEMENTS IN URINE. 233 matter on putrefaction ; (2) the leucomaines, which are ex- creted during life. These alkaloids are distinguished from alkaloids of vegetable origin by the Brouardel-Boutiny re- action (ferrocyanide of potassium and perchloride of iron). Vegetable alkaloids have no effect on this reagent, while leuco- maines on contact with it cause an intense blue coloration, morphia alone giving an intense reaction, and atropia a feeble one. The solution of Von Jaksch — Potass. Iod. ... ... ... ... 10 grammes Iodine 5 ,, Water 10 ,, — gives a green fluorescence on contact with leucomaines. Vegetable Alkaloids. — Tanret's solution forms the most delicate test for vegetable alkaloids. It gives a white precipi- tate, which disappears on the application of heat or the addition of alcohol. Trichloracetic Acid, which is sometimes employed as an albumen reagent, precipitates alkaloids when concentrated. This precipitate is dissolved by the addition of water, by heat, by the addition of alcohol, and by an excess of the reagent. The frequent administration of quinine as a therapeutic agent renders its presence in the urine important. When the residue of the evaporation with ether is treated with a drop of sulphuric acid, a marked blue fluorescence is an excellent test of quinine. The acid liquid gives the following further character- istic reactions of quinine : Chlorinated water and ammonia, a green colour ; chlorinated water with one drop of a solution of ferrocyanide of potassium and ammonia, a red colour. Instead of chlorinated water, which is very unstable, the liquor of Labarraque may be employed. Aristol is eliminated in the urine under the form of an alkaline iodide and of thymol. Its presence must be demon- strated by the tests employed for these agents. Bromides. — The action of chlorides on bromides being fre- quently obscured by organic matters, the following process recommended by M. Bruneau should be followed. Heat gently 234 THE UEINE IN HEALTH AND DISEASE. in a test-tube, and agitate. Chlorine gas is given off. To the aqueous solution add a little chloroform or sulphide of carbon ; agitate, and allow to repose. Bromine is indicated by the chloro- form which rests below the urine assuming a deep reddish- yellow colour, which disappears on agitation with potash or soda. Carbolic Acid appears in the urine after the internal administration of this drug in the form of phenyl-sulphate of potash. To demonstrate its presence, add a little hydrochloric acid to the urine and distil. To the distillate add bromine water, when a precipitate of tribromophenol is obtained. With perchloride of iron a blue coloration is produced. With Millon's reaction a red colour is obtained. A drop of aniline and a few c.c. of the liquor of Labarraque give a blue colora- tion, which appears slowly, but which lasts many weeks. Chloroform. — As the presence of chloroform in urine is a contested point, its mode of detection need not be described. Chloral. — Chloral is not naturally eliminated, nor in the form of chloroform. Its ultimate products are carbonic acid and urochloralic acid. The latter reduces Fehling's solution. Chlorate of Potash. — This salt is entirely eliminated by the urine. To demonstrate its presence, add to the urine a few drops of sulphate of indigo, dilute sulphuric acid, and a solution of sulphate of soda. The blue colour instantly disappears in presence of chlorate of potash. Iron. — The presence of iron is easily demonstrated in the urine. Add a few drops of nitric acid, and boil. Peroxide of iron is thus produced. Add a solution of ferrocyanide of potassium, when the characteristic coloration of Prussian blue appears. Iodides. — Iodides pass rapidly into the urine. To demon- strate their presence, add a few grains of starch. Agitate with freshly-prepared chlorine water, or one or two drops of fuming nitric acid. The iodine thus set free assumes a beautiful characteristic blue colour. An excess of nitric acid must be avoided. In place of nitric acid or chlorinated water, an alka- line hypochlorite, or perchloride of iron may be employed. Test for Iodine in Urine {Journal de Medicine de Paris, September 23, 1888).— To 10 c.c. of urine add 2 c.c. of dilute MEDICAMENTS AND ACCIDENTAL ELEMENTS IN UBINE. 235 sulphuric acid (one part to five of water) ; then add five drops of solution of starch freshly prepared. To this mixture add, drop by drop, a 1 per cent, solution of nitrate of potash, shaking the vessel. If the urine contain iodine, the addition of the first few drops will produce a violet or more or less intense blue coloration, which will disappear on the addition of a drop of 10 per cent, solution of hyposulphite of soda. The addition to the urine of a few drops of sulphuret of carbon intensifies the reaction. Iodoform may be found in the urine after the administration of this drug. Agitate the urine with ether ; spontaneous evapo- ration leaves iodoform as a residue. It is characterized by its odour, and, microscopically, by its hexagonal scales. Kairine. — A drop of perchloride of iron solution gives, with kairine, a violet colour, which rapidly turns into brown. Bichromate of potash gives a violet pigment which, with alcohol, gives a mauve solution. The addition, drop by drop, of a 10 per cent, solution of chloride of lime to urine acidified by acetic acid, and containing kairine, gives a fuchsine colour. Lithia. — Calcine completely a certain quantity of urine so as to obtain a white ash, which dissolve in dilute hydrochloric acid. Filter the liquid, evaporate to dryness, and dissolve in equal parts of ether and absolute alcohol. Evaporate the alcoholic liquor to dryness, and test the residue with the blow-pipe. If it contain lithia, a red flame is the result. Spectroscopic examin- ation reveals characteristic rays. Lead and Copper. — Evaporate the urine to dryness, and car- bonize the residue at as low a temperature as possible. Ignite in a porcelain capsule, and moisten from time to time with concen- trated nitric acid. On cooling treat the ash with water acidulated with a few drops of nitric acid, filter, and test the filtrate for lead and copper. With lead sulphuretted hydrogen gives a black or dark-brown precipitate, sulphuric acid a white precipitate, and chromate of potash a yellow precipitate. If the urine contain copper it presents a bluish colour, if the quantity is not ex- tremely feeble ; with sulphuretted hydrogen a black or brown colour results ; ammonia gives a greenish-blue precipitate, which dissolves in an excess of the reagent, giving an azure blue 236 THE UKINE IN HEALTH AND DISEASE. colour ; and ferrocyanide of potassium gives a brown or reddish- brown colour. Mercury. — Acidulate the urine with hydrochloric acid, and add powdered zinc, which precipitates all the mercury. Wash the precipitate with hot water, then with alcohol and ether, and treat after Ludwig's method. Secondly, acidulate the urine with hydrochloric acid and heat. Cool, and heat anew. Plunge into the liquid several times a thin metallic plate com- posed of copper and zinc, on which the mercury deposits. Wash the plate, and expose to iodine vapour, when iodide and biniodide of mercury are formed ; or treat the plate after Marsh's method. Naphthaline. — If to urine containing naphthaline a few drops of ammonia be added, or soda, a beautiful blue colour results. When naphthaline is administered as a drug the urine becomes of a characteristically dark colour. Naphthol and other Phenols. — Treat a given quantity of urine with half its volume of chloroform, agitate gently, and pour into a decantation apparatus. The decanted chloroform is received in a test-tube, and a pastil of caustic potash is added. Characteristic coloured spots result, varying with the nature of the phenol (Desquelle, Repertoire de Pharmacie, 1890, p. 101). With ordinary phenol, a rose colour. With thymol, a deep violet colour. With resorcine, a rose colour. With hydroquinon, a golden yellow colour. With naphthol (x), a sky-blue colour. With naphthol (b), a greenish-blue. With pyrogallol, a violet colour. With creosote, a violet colour. With guaiacol, a rose-violet colour. Yvon commends the subjoined as naphthol tests : (i.) Acid nitrate of mercury 5 grammes. Nitric acid ... ... ... ... ... 15 ,, (ii.) Saturated solution of nitrate of potash ... 10 ,, Sulphuric acid ... ... ... ... 5 ,, These two tests give with naphthol a red colour. MEDICAMENTS AND ACCIDENTAL ELEMENTS IN UEINE. 237 Bethol, or Salicylate of Naphthol. — Bethol is eliminated in the urine as naphthol, and salicylic and salicyluric acids. Grenouillet (Bepertoire de Pharmacie, 1890, p. 470) recom- mends the following process for its isolation : Eeduce 500 c.c. of urine to the volume of 150 c.c. ; after cooling, filter, and agitate the liquid with its volume of ether. Evaporate, and dissolve the residue in boiling water. After cooling, salicylic acid is revealed by perchloride of iron (vide Salicylates). Otherwise add to the urine 2 per cent, of sulphuric acid and distil. Agitate the distilled product with chloroform. This liquor gives with caustic potash the characteristic blue colour of naphthol. Phenacetine. — Strongly acidulate the urine with hydrochloric acid, and heat. On cooling add from one to two drops of a per- chloride of iron solution, when a reddish- brown coloration is produced. Or to 2 c.c. of urine of an acid reaction add from four to five drops of a solution of chromic acid (3 per cent.). At the point of contact of the two fluids a brown coloration appears. Salicylates. — A few drops of a solution of perchloride of iron cause a violet coloration in urine containing a salicylate ; but if the salicylate exist in feeble proportion, and the urine con- tain a large proportion of phosphates, a precipitate of phosphate of iron forms, which obscures the salicylate reaction. In this case the salicylic acid must be isolated. To accomplish this, add to 100 c.c. of urine from six to eight drops of hydrochloric acid, and agitate gently with 6 c c. of ether. After sufficient repose the ether is decanted and poured out on a saucer containing a few drops of a 10 per cent, solution of perchloride of iron. After evaporation of the ether a beautiful violet coloration ensues. Salol, or salicylate of phenol, is not normally voided with the urine. The derivatives of salol reduce Fehling's solution, and deviate the plane of polarization to the left. To distinguish glucose in presence of salol, the urine decolourized by a tenth part of its volume of subacetate of lead is placed in a tube with 5 centigrammes of hydrochlorate of phenylhydrazine and 0'20 of pure soda. The liquid becomes of a yellow colour, and is heated for half an hour on a water-bath. It is then poured into 238 THE URINE IN HEALTH AND DISEASE. a suitable glass vessel and cooled, when, if it contain sugar, a crystalline deposit results, recognisable by the microscope. "With salol the deposit is amorphous. Saccharine. — Agitate the urine with a few drops of sulphuric acid, and then with a mixture of ethylic and petrolic ether. Evaporate the ethereal liquid, and dissolve the residue in a little hot water. The solution possesses a sugary sweetness most marked in the case of saccharine. Neutralize the residue with carbonate of soda, and treat with a small excess of nitrate of mercury. A saccharinate of mercury results, which may after washing be collected and dried on a filter. Place this in a test- tube, and add twice its volume of resorcine. Add a few drops of sulphuric acid, and heat. Divers colours result, the mass becomes resinous, and gives off sulphurous acid. Allow the remainder to cool, dilute with water, and saturate with potash or caustic soda. There results a reddish-brown liquid with green fluor- escence. This fluorescence becomes manifest if a few drops of the liquid be added to a tube containing water. Strontium. — The urine concentrated to a tenth of its volume is filtered after cooling. To a portion of it which is perfectly limpid, a few drops of neutral chromate of potash solution are added. If there be no result, it may be inferred that no salts of barium are present. To another perfectly limpid portion of urine a few drops of sulphuric are added. A precipitate of sulphate of strontium is formed. Ignite with carbon, and a transformation into sulphide takes place. Dissolve the residue in hydrochloric acid, and examine for strontium spectroscopi- cally. Tannin. — Tannin is eliminated in the urine in the form of gallic acid. With perchloride of iron, gallic acid in urine gives a black-blue precipitate. Alkalies give a brown and black colour. Turpentine with protochloride of antimony gives a red colour; and M. Loison (Bejp. de Pharm., 1890) recommends the following test process : Evaporate 500 c.c. of urine on a water- bath to the consistence of an extract. To the residue add 10 c.c. of boiling alcohol, filter, and reduce by evaporation to 5 c.c. Add to these 5 c.c. a few drops of hydrochloric acid, and place MEDICAMENTS AND ACCIDENTAL ELEMENTS IN URINE. 239 in a fine tube containing some crystals of proto chloride of antimony.- Gently heat the tube, and after a minute's boiling, if the urine contain turpentine, an intense red colour appears. Rhubarb. — After partaking of rhubarb, a deep yellow colour is imparted' to the urine, sometimes resembling the urine of jaundice. The addition of an alkali to such urine causes a red colour. The following reactions distinguish rhubarb from santonine : In the case of rhubarb, senna, etc., the coloration produced by the alkali persists for more than twenty -four hours. The coloration appears promptly with soda or ammonia. Eeducing agents, such as powder of zinc and sodium, cause the colour to disappear. Baryta solution and lime-water precipitate the colouring matter. Santonine. — The coloration caused by alkalies does not persist beyond twenty-four hours, and is slow to appear. Eeducing agents do not cause the colour to disappear. Baryta and lime- water do not precipitate the pigment, and the liquid becomes limpid on repose, but the red colour persists. If the urine be acidified with sulphuric acid and agitated with amylic alcohol, no coloration results in the case of santonine, while in the presence of rhubarb a yellow colour is the result. Thalline. — Urine containing thalline exhibits a brownish tint with greenish reflection. To identify its presence, treat the urine with chloroform or with ether, decant, and evaporate in a porcelain crucible, when contact with perchloride of iron will give a beau- tiful green colour. Urethan. — Agitate 500 c.c. of urine with a sufficient quantity of ether. Decant, wash with distilled water, and completely evaporate. Add to from 10 to 20 c.c. an excess of potash. To this add a solution of perchloride of mercury, when a more or less abundant white precipitate is obtained. Filaments of Tissues ; Grains of Starch. — These bodies are easily recognised by their chemical and microscopic characters. Cotton fibres are coloured blue by iodine and sulphuric acid. Starch gives a characteristic blue colour with a solution of iodine. APPENDIX. Conversion of Grammes into Grains and Vice Versa. Grammes to Grains. 1 = 15-43235 2 = 30-86470 3= 46-29705 4 = 61-72940 5= 77*16175 6= 92-59410 7 = 108-02645 8 = 123-45880 9 = 138-89115 Grains to Grammes and Milligrammes. 1 = 0-6480 or 64-80 o -0-12958 „ 129-58 3 = 0-19437 „ 194 37 4 = 0 25916 „ 259-16 5 = 0-32395 „ 323-95 6 = 0-38874 „ 388-74 7 = 045353 „ 453-53 8 = 0-51832 „ 518-32 9 = 0-58311 „ 583-11 Comparison of Measures (English into Metric). 1 minim =0*5916 c.c. 1 fluid drachm = 3*5495 c.c. 1 fluid ounce =28*396 c.c. 1 pint =567*92 c.c. = 0*56792 litre. 1 quart =1'3584 litre. 1 cubic inch =16*386 c.c. Comparison of Weights (Metric into English). 1 milligramme =0*01543 grain ( = nearly the ^th) 1 centigramme = 0*15432 grain 1 decigramme =1*54323 grains 1 kilogramme =35*27395 ounces (Avoirdupois) or 2*2046213 lbs. (Avoirdupois) APPENDIX. 241 To convert grammes per litre into grains per gallon, multiply by 70. To convert grains per gallon into grammes per litre, multiply by 0-014286. To convert grammes per fluid drachm into grains per fluid ounce, multiply by 123-46. 1 millimetre = 0*03937 inch 25*4 mm. =1 inch Johnson's ' Analyst's Laboratory Companion.' To convert degrees of Fahrenheit's thermometer into those of the Centigrade scale, subtract 32 and multiply by % ; and conversely to convert Centigrade readings to Fahrenheit scale, multiply by § and add 32. 16 I N D E X. A. Acetanilide, elimination of, 232 Acetone, 183 pathological significance of, 185 properties of, 183 tests for, 184 Acetonuria, 185 forms of, 186 Acid, acetic, 187 acetylacetic, 184 benzoic, 93 butyric, 187 carbolic, 96 carbonic, 117 cholalic, 192 choleic, 192 cholic, 193 formic, 187 glycocholic, 192 hippuric, 83-86 lactic, 187 omicholic, 99 oxalic, 93 oxaluric, 91 phenic, 96 phosphoglyceric, 110 phosphoric, 107 propionic, 187 saccharic, 160 salicylic, 237 succinic, 92 sulphuric, 105 tannic, 41 taurocholic, 192 uric, 70 valerianic, 187 Acidity of urine, 32 Agnosti's reaction, 167 Albumen, 118 coagulation of, by heat, 121 coagulation of, by nitric acid, 123-125 nitro-prussiate of soda, test for, 130 picric acid, test for, 127 potassium ferrocyanide, test for, 128 Roch's test for, 131 Spiegler's test for, 131 Albumen, Stutz's test for, 131 Tanret's test for, 126 quantitative analysis of, 136-145 pathological significance of, 145-155 therapeutic indications of, 146 Alcohol, elimination of, 230 Alkalinity of urine, 36 Alkaloids, cadaveric, 152 Alkaptone, 96 Allantoine, 91 Alloxan, 73 Almen's sugar test, 166 Ammonia in urine, 115 Amylamine, 182 Antifebrine, elimination of, 232 Antimony, elimination of, 232 Antipyrine, elimination of, 231 Aristol, elimination of, 233 Arsenic, elimination of, 232 Ascaris lumbricoides, 213 B. Bacillus of tuberculosis, 213 Bacillus urese, 214 Bile, elements of, 188 Bilharzia haematobia, 213 Bilifuscine, 190 Bilihumine, 190 Biliprasine, 189 Bilirubine, 188 Biliverdine, 189 Biuret reaction, 152, 153 Blood-corpuscles in urine, 205 Bodo urinarius, 213 Bromides, elimination of, 233 Butyric acid, 187 C. Calculi, analysis of, 226 of carbonate of lime, 227 of cholesterine, 227 of cystine, 226 of oxalate of lime, 227 of phosphate of ammonia and mag- nesia, 227 INDEX. 243 Calculi of ammonium urate, 226 of calcium urate, 228 of magnesium urate, 228 of potassium urate, 228 of sodium urate, 228 of uric acid, 226 of xanthine, 226 urinary, 226 Cells, epithelial, of the kidney, 210 of the ureter, 210 of the urethra, 211 of the vagina, 210 Cercomonas urinarius, 213 Chloral, elimination of, 234 Chloride of sodium, 103 analysis of, 104 pathological significance of, 105 properties of, 103 Chloride of zinc and creatine, 87 of creatinine, 88 Chlorides, 103 ' of calcium, 103 of magnesium, 103 of potassium, 103 Chloroform, elimination of, 234 Cholesterine, 193, 194 analysis of, 194 calculi of, 227 Colour of urine, 25 Concretions, 215 Copaiba in urine, 126 Corpuscles of blood in urine, 205 Creatine, 86 Creatinine, 86 analysis of, 90 extraction of, 88 variations of, 90 Crismer's sugar test, 165 Cylinders or casts, 196 amyloid, 197 blood, 199 epithelial, 194 fatty, 197 granulo-fatty, 197 hyaline, 197 mucous, 198 prostatic or spermatic, 199 pathological significance of, 199 Cylindroids, 198 Cystine, 179 analysis of, 180 calculi of, 226 properties of, 179 sediments of, 217 sediments (gravel), 229 D. Day's test for pus, 209 Degree of acidity of urine, 32, 33 of alkalinity of urine, 36 Density of urine, 31 estimation of, 31 variations in, 30 Dextrine, 159 Dextrose, 159 Diabetes, 158 glycopolyuric, 82 insipidus, 158 saccharine, 156 toxic, 174 Diathesis, oxalic acid, 95 phosphatic, 113 uric acid, 82 Distoma haematobium, 13 Diuretics, action of, 22 Dumb-bell crystals, 94 Dyslisine, 193 E. Bchinococci in urine, 213 Ehrlich's reaction, 192 Elements, accidental, in urine, 230 of the bile in urine, 194 organic, in urine, 203-214 pathological, in urine, 196 200 Epithelium in urine, 209-211 Esbach's tubes, 144 Excretion of urine, 17 mechanism cf, 17-22 F. Fat, 195 Fehling's sugar test, 163 Ferrein, pyramids of, 9 Ferrocyanide of potassium test for albu- men, 128 Fibrine in urine, 150 Filaria sanguinis hominis, 195, 213 Fluorescence of urine, 27 G. Galacturia, 195 Gases in urine, 117 Gerrard's glycosometer, 172 Globinuria, 148 Globules of blood in urine, 205 of pus in urine, 208 Globuline, 147 analysis of, 148, 149 pathological significance of, 150 Glucose, 158 extraction of, 161 properties of, 160 tests for, 161, 168 Glycochole, 45, 192 Glycocholic acid, 192 Glycosuria, 159 alimentary, 159 pathological significance of, 173 physiological, 159 simulated, 176 therapeutic indications in, 176 toxic, 159 Gmelin's reactionjfor bile, 190 Gravel, forms of, 216-225 Guaiacum as a blood test, 204 244 INDEX. H. Haematoidine, 225 Hematuria', 203 Hsenrin, 204 Hsemoglobine, 204 Hemoglobinuria, 203 Hammorstein's process for estimation of globuline, 149 Haycraft's method for estimating uric acid, 78 Heller's test for albumen, 124 for blood, 203 Hemi-albumose, 154 analysis of, 154 properties of, 154 Hippuric acid, 83 extraction of, 84 quantitative analysis of, 85 physiology and pathology of, 85 tests for, 84 Hoppe-Seyler's sugar test, 166 Huppert's* reaction (bile), 191 Hydrobilirubine, 97 Hydrogen-peroxide in urine, 116 Hydroquinone, 96 Hydruria, 29 Hypobromite method for urea estima- tion, 57 Hypoxanthine, 91 I. Indican, 99 Indigo blue, 100 red, 100 sugar test, 166 Indirubine. See ' Urrhodine ' and 'In- digo red.' Indol, 97 Inosite, 178 analysis of, 178 properties of, 178 Iodine and iodides, elimination of, 234 Iodoform, elimination of, 235 Iron, elimination of, 234 J. Jaworowski's test for albumen, 131 K. Kairine, elimination of, 235 Kidney, circulation of blood in, 13-15 size of, 2 structure of, 3-13 weight of, 2 L. Lactic acid, 187 Lactose, 177 Lecithine, 195 Lechine's reaction (blood), 204 Leucocytes in urine, 208 Levulose, 177 Lieben's reaction (acetone), 185 Liebig's urea process, 53 Lime, estimation of, 114 Lipuria, 195 Lithia in uric acid diathesis, 83 M. Magnesia, 114 triple phosphate of, 109 Mechanism of urinary secretion, 17-21 Melanuria, 187 Mercury, elimination of, 236 Methsemog^obine, 206 Micrococci^ urine, 84-214 Milk sugar K 177 Millon's reaction (urea), 53, 153 Moore's test for sugar, 161 Mucine, 150 JVIurexide reaction, 73-77 Muscle sugar, 178 N. Naphthaline, elimination of, 236 Naphthol and other phenols, elimination of, 236 Neisser's Gonococcus, 214 Nitrates and nitrites in urine, 116 Nitric acid test for albumen, 124 Nitrogen, total elimination of, 116 O. Odour of urine, 25 Orthonitrobenzaldehyde reaction, 184 Ost's sugar test, 163 Oxalate of lime, 94 analysis of, 95 calculi of, 221 Oxaluric acid, 91 Oxyhemoglobin e, 206 Oxyuris vermicularis, 213 P. Paracresol, 96 Paraglobuline, 147 Penicillium glaucum, 175 Peptones, 152 analysis of, 152 properties of, 152 Peptonuria, 154 Peroxide of hydrogen in urine, 116 Pettenkofer's bile reaction, 193 Phenic acid, 96 Phenyl-hydrazine reaction, 167 Phosphates, 107-113 alkaline and earthy, 107 qualitative analysis of, 110 quantitative analysis of, 110 Phosphatic diathesis, 113 Phosphaturia, 113 Phosphogly eerie acid, 110 Phosphoric acid, 107-110 estimation of, 110 Picric acid test for albumen, 110 for sugar, 167 INDEX. 245 Pigments, biliary, 188 urinary, 97 Piperazine in uric acid diathesis, 83 Pohl's test for globuline, 149 Polyuria, 29 Potash, estimation of, 114 Process of Bod eker. (albumen), 139 of Brandberg (albumen), 141 of Esbach (albumen), 143 of Hammarstein (albumen), 149 of Leconte (urea), 51 of Liebig (urea), 54 of Millon (urea), 53 of Salkowski-Ludwig (uric acid), 79 of Tanretand Troyes (albumen), 138 Propeptone, 154 Prostatitis, urethral discharge in, 211 Ptomaines, 152 Purdy's sugar estimation, 164 Pus in urine, 208 Day's test for, 209 Pyrocatechin, 96 Q. Quantity of urine (normal\ 28 agencies influencing the, 29 R. Reaction of Adamkievicz (albumen), 132 of Agnotsti (sugar), 167 of Almen (sugar), 166 of Bayrac (uric acid), 79 of biuret (peptones), 152, 153 of Bottger (sugar), 165 of Chautard (acetone), 184 of Dietrich (uric acid), 77 of Ehrlich (bile), 192 of Fehling (sugar), 163 of Gmelin (bile), 190 of Hoppe -Seyler (sugar), 166 of Lieben (acetone), 183 of Millon (urea, albumen), 53, 121 of Moore-Heller (sugar), 160 of Mulder (sugar), 167 of murexide (uric acid), 73, 77 of Pettenkofer (bile), 193 of Rosenberg (uric acid), 77 of Scherer (inosite), 178 of Trommer (bile), 162 of Worm-Muller, 160 of Zahsr, 145 Residue, solid, of urine, 31 Rhubarb, elimination of, 239 Rosaniline test for acetone, 184 Rosenbach's bile reaction, 191 S. Saccharine, elimination of, 238 Saccharomyces of urine, 214 Safranin sugar test, 165 Salicylates, elimination of, 237 Salol, elimination of, 237 Santonine, elimination of, 239 Sarcine or ypoxan ne, 91 Sarcinse urese, 214 Schiff's test for uric acid, 77 Schmiedeberg's reaction, 165 Secretion of urine, theories of, 17-21 Sediments, 215 of bilirubine, 224 of carbonate of lime, 218 of cholesterine, 225 of cystine, 223 of hoematoidine, 225 of indigotine, 225 non-organized, 216 of oxalate of lime, 221 of phosphate of lime, 223 of triple phosphates, 222, 223 of tyrosine, 224 of urates, 219-221 of uroglaucine, 225 of xanthine, 224 Serum albumen, 120 Silica in urine, 116 Skatol, 97 Soda, estimation of, 114 in urine, 113 Sodium, chloride of, 103 ^Spectroscope, 206 Spermatozoa, 199, 211 Strongylus gigas, 213 Strontium, elimination of, 238 Succinic acid, 92 as an albumen test, 130 Sugar of diabetes, 160 of milk, 177 of muscle, 178 of raisin, 176 optical analysis of, 173 pathological significance of, 173 quantitative analysis of, 169-171 Sulphates, 105 Sulphuretted hydrogen in urine, 203 Sulphuric acid, 105 T. Tanret's solution, 126 Taurine, 192 Temperature of urine, 28 Thalline, elimination of, 239 Toxicity of urine, 38 Transitory albuminuria, 155 Transparency of urine, 24 Trominer's sugar test, 162 Tube casts in urine, 198 Turpentine, elimination of, 238 Tyrosine, ISO properties of, 180 sediments of, 218 tests for, 181 U. Uraemia, 68 Urate, acid ammonium, 75 acid calcium, 75 acid magnesium, 75 acid sodium, 74 246 INDEX. Urate, lithium, 76 Urates, 74 sediments of, 218 Urea, 43, 44 artificial production of, 46 chemistry of, 46, 47 modification of amount of, 45 nitrate of. 48 oxalate of, 48 physical properties of, 47 preparation of, 48 quantitative analysis of, 41 by Leconte's process, 51 by Liebig's process, 53 by Yvon's process, 58 Ureometer of Doremus, 60 of Gerrard, 59 of Mercier, 62 of Noel, 61 of Regnard, 66 Urethan, elimination of, 239 Uric acid sediments, 221 Urina chyli, 25 potus, 25 sanguinis, 25 Urine, accidental elements of, 39 colour of, 25 density of, 28 normal, 24 transparency of, 24 toxicity of, 38 Urinometer, 31 Urobiline, 97 Urochrome, 99 Uroerythrine, 99 Uroglaucine, 100 UrohsematoporphTrine, 98 Uromelanine, 99 Uropittine, 99 Urrhodine, 100 V. Volume of urine, 28 in health, 29 in disease, 30 Weyl's test for creatinine, 89 X. Xanthine, 90 calculi of, 226 sediments of, 224 Xanthogen reaction, 231 Xanthoproteic reaction, 121 Z. Zahor's method for estimation of albu- men, 145 Zeller's test for melanine, 187 Zouchlos's albumen test, 129 ERRATA. Page 38, line 15, for 1 he observed ' read_ ' Bonchard observed,' etc. ,, 145, ,, 1, for ' Zohar ' read 1 Zahor.' ,, 165, second line from bottom of page, for 1 Bottiger ' read 1 Bottger.' ,, 213, ,, ,, ,, ,, ,, for 'Ascaridis ' read 4 Ascaris.' ,, 214, line 8, for ' Bacillus urinae ' read ' Bacillus ureae.' THE END. BAILLIERE, TINDALL AND COX, KING WILLIAM STREET, STRAND. BY THE SAME AUTHOR. >»<00 Bright's Disease. London : J. & A. Churchill. Phila- delphia : Lindsay & Blakiston. I This volume comprises a series of six lectures on Bright's Disease of the Kidney, delivered at the Royal Infirmary of Glasgow, and afterwards published in the Medical Press and Circular. In the present form they have been revised and amplified, and cannot fail to be acceptable to every busy practitioner who has not time to consult a large treatise. The subject is very interestingly, comprehensively, and practically treated.' — New York Medical Record. I I have read your work (Lectures on Bright's Disease) with much pleasure, and consider the book will be most valuable to the student. The facts are put very lucidly, and the reasoning is in a concise form, showing that you must be a good teacher ; and T hope you have, or mean to obtain, a lectureship in some good school of medicine.' — George Owen Bees } M.D., F.B.S., Senior Consulting Physician to Guy's Hospital. Observations on Therapeutics and Disease. London: Churchill & Sons. ' Dr. Black is one of those thinkers who ought to be encouraged. . . . We have said that we think such an attempt as Dr. Black's is one to be encouraged. We think so because boldness of thought, and a dis- position to handle the problems of disease and of health in a large spirit, are very necessary to that great reform in therapeutics which we all hope to see. There is much ability in his pamphlet, and it will be an immense gain to practical medicine if he succeeds in stirring up our scientific therapeutists to look at questions of medication in a broad way, and in relation to the great physiological states, instead of merely ticketing remedies with specific titles, and inducing the hapless practi- tioner to discharge them at a supposed peccant organ, as a boy might aim a pea from a pop-gun.' — Practitioner. ( 2 ), ' * Dr. Black's essay displays an extensive knowledge of his subject, and though many of his views are necessarily open to controversy, they are well worth consideration.' — Brit, and For. Med.-Chir. Rev. ' The book shows that its author possesses considerable speculative ability, and that he entertains a healthy hatred of everything savour- ing of refinement in diagnosis, as well as of all those who, in the pursuit of new remedies and theories, neglect to exhaust the curative capacities of known drugs. ... It is suggestive, and written with considerable vigour.' — Edin. Med. Jour. ' We have a thoughtful and carefully written pamphlet from Dr. Black on " Therapeutics and Disease." . . . There is a great deal of hard reading in his pamphlet, and we shall not attempt to do justice to the author in tracing his observations throughout. His endeavour is to indicate certain conditions of the system which give, as it were, distinct opportunities for the attack of diseases, and then to show how remedies which will cure these diseases do so by restoring the system to its properly balanced state. We are compelled to place Dr. Black's classification thus vaguely, for there is too much in it to analyze it throughout.'— Chemist and Druggist. ' Your " Observations on Therapeutics and Disease " I have read with much pleasure.' — Sir Wm. S. Savory, F.R.S., Surgeon and Lecturer on Surgery, St. Bartholomew's Hospital, London. 1 There is no doubt that such an effort as yours will end in that con- summation so devoutly to be wished — the putting of the study of the physiological action of remedies on a more rational basis.' — T. E. Thorpe, Prof, of Chemistry, Anderson's University, Glasgow. * I have read, and re-read, your pamphlet, and find it excellent.' — J. Hjaltelin, M.D., Chevalier of the Legion of Honour, Knight of the Order of Dannebrog ; Chief Physician, Iceland. Urinary and Eeproductive Organs. Second Edition. London : Churchill & Sons. Philadelphia : Lindsay & Blakiston. 'This volume- -the expansion, as its author tells us, of a proposed article for the British Medical Journal — is evidently written by a gentleman of considerable practical experience, deep thought, and extensive reading. . . . The style of the author is^easy and agree- able. ... On the whole, his work is a valuable contribution to medical science, and being penned in that spirit of unprejudiced philosophical inquiry which should always guide a true physician, admirably embodies the spirit of its opening quotation from Professor Huxley.' — Philadelphia Medical Times. 1 We like the tone of the book, though it advocates many proposi- tions not accepted by the profession. Even these, we think, will • ; ( 3 ) .. provoke discussion, and so hasten the time when the functional .diseases of the male shall be. as carefully studied and treated as those of the female.' — Michigan Univ. Jour. ' There is so much cleverness, bonhomie, and frankness, and ap- parent honesty of purpose and distaste for quackery, that hostile criticism is disarmed. ... It is an interesting, original, and will probably prove a useful work. With Chapter IV. begins the real work of the author, on The Pathology and Treatment of Nocturnal Enuresis and Spermatic Incontinence. This is followed by a well- reasoned and manly discussion of the unsavoury subject. The practical observations on treatment are sensible. The book is nicely got up, and the Table of Contents and Index are admirably arranged.' — Edin. Med. Jour. 4 Dr. Black deserves all praise for the manliness, heartiness, honesty of purpose, and scientific zeal with which he has treated a subject which has become distasteful from its associations, which has been too much shunned by our profession, and which has unfortunately fallen almost altogether into the hands of charlatans. . . . Dr. Black's book contains much useful information, and will doubtless prove interesting to many readers.' — Birmingham Medical Review. c This is an important work, showing extensive research, and con- veying much information.' — The Doctor. 4 There are some points in reference to the functional disorders of the reproductive system that are continually forcing themselves upon medical men, but which few practitioners care to investigate. Some of these have been fully discussed in this and other medical journals, but, unfortunately, such topics are apt to be neglected, and hence fall into the hands of those least qualified to discuss them. We have had by us for a long time a volume by Dr. Campbell Black, in which the topics we have alluded to are freely discussed, and which is, perhaps, the best work of reference respecting them for medical men.' — Med. Press and Circular. ' There is a large amount "of useful information in the book. The author has evidently read a good deal, and can think for himself. . . . The work seems to have been written by a professional man for profes- sional men, not by a charlatan for the public. On the whole, we are disposed to regard the book as a good, well-intentioned one.' — Brit, and For. Med.-Chir. Rev, * I have read your very valuable work with the greatest pleasure and profit.' — Professor Louis A. Sayre, New York. mil