SAMUEL LILIENTHAL, M. D., 230 West 25th Street. THE PROPERTY OF l CnllecB of tie Pacific. MEDICAL A MANUAL OF CHEMICAL PHYSIOLOGY. A MANUAL CHEMICAL PHYSIOLOGY ITS POINTS OF CONTACT WITH PATHOLOGY. J. L. W. THUDICHUM, M.I). NEW YORK: WILLIAM WOOD & COMPANY, 27 GREAT JONES STREET. 1872. \ PREFACE. THE first part of this little treatise was written and printed as the introduction to my " Researches intended to promote an Improved Chemical Identification of Diseases," which have been published in several numbers of the annual " Report of the Medical Officer of the Privy Council." It has been found so useful in my experience as a teacher, that I have, with the permission of Mr. Simon, ventured to reproduce it in the present form. It is a complete but concise epitome of the branch of science commonly termed " physio- logical or animal chemistry," and will be found to contain its latest acquisitions. Any medical student who possesses the information which it contains will be enabled to meet the requirements, so far as concerns this particular subject, of any of the examining and licensing bodies in this country and abroad. To the student in Chemistry, Physiology, or Science, it offers a ready help to the acquisition of elementary know- ledge, upon the basis of which he can afterwards place the superstructure of more extended and detailed 13555 VI PREFACE. studies. To my colleagues of the Medical Profession it will afford an easy bird's-eye view of the chemical features of the field of their thoughts and action. Its perusal will involve no unreasonable tax upon the time of any reader or student, and occasional reference to particular points is facilitated by marginal notes and a short alphabetical index. The second part of the work is an Analytical Guide for the use of those who desire to make themselves practically acquainted with the phenomena and con- stituents of animal bodies. It is therefore not de- scriptive in the sense in which ordinary chemical text- books may be said to be so, but prescriptive in the style and manner of pharmacopoeias. It directs the student how to proceed in order to arrive at a certain result, leaving him in most cases to appreciate the result of his operation by his own reflection. The guide is perhaps the most elementary that could be written for any practical purpose, and yet I think it improbable that ordinary students of medicine will easily go through the whole of its matter in the laboratory. I hope, therefore, that teachers of chemistry who will make use of the Guide in their classes will select the reactions and analyses to be performed by each student according to his knowledge, ability, and intentions. This little treatise summarises much of the method PREFACE. Vll pursued, and many of the results arrived at in my laboratory during many years of patient inquiry. In the compilation of the Analytical Guide I have received much valuable help from my esteemed assistants, Mr. F. J. M. Page, and Mr. C. G. Stewart, for which I here express to them my sincere thanks. THE AUTHOR. 3, PEMBROKE ROAD, KENSINGTON, W. ; April, 1872. CHEMICAL PHYSIOLOGY, AND ITS POINTS OF CONTACT WITH PATHOLOGY. THE food of man, variously prepared by mechanical Digestion. processes and chemical operations (cooking), is com- minuted in the mouth by chewing. At the same time it is mixed with a variety of fluids, some of which have chemical powers and predispose the food to a change, while others serve mechanical objects only. The mixture of these fluids is termed saliva ; saliva. but however homogeneous may appear that mixture, the properties of its components are very various. For the secretion of every particular kind of glands, of which there are four, differs , and the secretion of one and the same gland or set of glands may vary according to the agencies which call them into action. Underneath the forepart of the tongue is secreted from one and the same duct the saliva of a gland which lies under the tongue (sublingual) , and that of two other glands which lie farther back on both sides of the tongue underneath the lower jaw (submaxillary glands). To collect either of these secretions little 1 2 CHEMICAL PHYSIOLOGY. tubes have to be carefully introduced into the respective ducts, which is a matter of some difficulty. For this reason the chemical composition of the secretions of the separate glands is very imperfectly known. Ex- periments upon animals have shown that these glands can give four different kinds of secretion, according to the nerves which are irritated for the purpose. One nerve, a branch of the facial, and a continuation of the chord of the tympanum, on irritation causes a clear, slightly ropy secretion from the submaxillary glands. sauTa dal ^is "chordal" saliva contains about 4 per cent, of solid matters, of which 1*5 are globuline, mucine, and coagulable albumen ; 2*5 per cent, are mineral, mainly alkaline chlorides and lime-salts ; of these latter the carbonate, dissolved in excess of carbonic acid, fre- quently decomposes in the mouth, and deposits crusts of lime carbonate upon the teeth, which are popu- ia7va athetic l ar ty called tartar. On irritation of the sympathetic nerve the submaxillary glands secrete an opaque very tough saliva. This contains from 15 to 28 per mille of solids, amongst which is mucine, and granules or roundish lumps of an albuminous matter, and much S! nic f ree alkali. The third kind of saliva is that which flows when the submaxillary ganglion is made the centre of a reflex action which works by way of the lingual nerve. This is the only secretory act without the intervention of cerebro-spinal influence that is known at present. The fourth kind of saliva is the paralytic " paralytic " or thin watery fluid which is secreted under the influence of nervous paralysis, caused either by degeneration, or poisoning, or wounds which separate CHEMICAL PHYSIOLOGY. 6 the secretory nerves. Its composition is not yet ascertained. The mixture of sublingual and submaxillary saliva in man (not in animals) contains rhodanate or sulpho- cyanate (also termed rhodanide or sulphocyanide) of potassium and sodium C N K S, and C N Na S, recog- nised by the red colour which iron-chloride imparts to saliva, or to the distillate obtained from it with acids. This phenomenon admits at present of no particular theory. The saliva which is secreted by the parotid glands can easily be collected by the introduction of canulae into the ducts. It is an alkaline, hardly viscous fluid, which contains a little albumen, some globuline, a particular ferment termed ptyaline, but no mucine. It contains much rhodanate, and is the most suitable material for preparing the distillate of rhodanic acid. It contains, water 995*3; solids 4*7; of these are organic 1*4; mineral 3*3 ; of the latter there is lime carbonate 1/2. The parotid saliva transforms starch into sugar by means of the ferment termed ptyaline. This is the only agent in saliva which has that power. It can be isolated by adding phosphoric acid and subsequently lime to saliva. Ptyaline adheres to the phosphate, is washed out by water, and precipitated by alcohol. It contains nitrogen but is not albuminous, refusing to yield the xanthoproteic acid reaction with nitric acid. The diastase of malt has a similar action used in trade fermentations. An interesting and important applica- tion has lately been made of diastase by Baron Liebig, for the production of a food for infants, which supplies 4 CHEMICAL PHYSIOLOGY. efficiently the want of alkali and ptyaline in the diges- tive juices of children who are being brought up with- out mother's milk, or with such as is not in a healthy state. Diastase acts best at 66 C, while ptyaline is destroyed at 60 C. An agent similar to ptyaline is emulsine, or synaptase of almonds, which has been recommended as a dietetic remedy in diabetes. But it does not seem to affect starch in any way, although decomposing amygdaline and salicine. Oil of bitter Prassic Amygdaline. "Water. almonds. acid. Sugar. Salicine. Water. Saligenine. Sugar. In these transformations sugar is a collateral pro- duct, while in that of starch by ptyaline or diastase it is the only product. starch. Starch consists of two bodies, which in the little granules are disposed in alternating layers. The first is granulose, and has the property of being coloured blue at once by free iodine. The second is cellulose, not coloured blue by iodine at once, but only after sulphuric acid or zinc-chloride has been allowed to act upon it. When unboiled starch is mixed and digested with saliva for days, the granulose is dissolved out of the corpuscles and transformed into dextrine and sugar, and the cellulose only is left. At higher temperatures this also is changed. Boiled starch is more easily transformed, as the granules are burst and admit the altering juices between their layers with CHEMICAL PHYSIOLOGY. 5 facility. The first symptom of the addition of saliva to boiled and cooled (to 40 C) starch or pap is increased fluidity, indicating the formation of soluble starch and dextrine. At a later period only sugar is formed, according to the following formulse : Starch (synonym = amylon) C 6 H IO 5 Soluble starch Dextrine . . Dextrine. Water. Sugar. C ) H?= C " The same formula as starch. 'Amongst the products of degeneration of the spinal marrow in locomotor ataxia, there are bodies resembling starch corpuscles, but consisting entirely of cellulose. I had an opportunity afforded me of examining such a case, in which the sense which in physiology we now term the sense of pressure was almost entirely lost, while the sense of pain and the sense of heat and cold persisted. On examining microscopically, and by means of sulphuric acid and iodine, thin sections of the spinal marrow, I found in various parts of it agglo- merations of blue bodies imitating in a remarkable manner wheat-starch coloured blue by iodine. The term amyloid is perfectly correct as applied to this particular degeneration. The reaction of these bodies, however like to that of amylum, is not that of amylum itself, for the latter is coloured blue by iodine alone, while these bodies require the concurrence of sulphuric acid and iodine. The secretion of the salivary glands mixed with Mixed Baliva - the mucus secreted by little follicles, in the mem- 6 CHEMICAL PHYSIOLOGY. branes of the cavity of the mouth, constitutes mixed saliva. This can be collected in quantity by irritating the fauces with a feather, and producing vomituritions. It does not reduce alkaline copper solution, but retains a little copper oxyde in solution when cupric salt and alkali only are added. It transforms starch into sugar, so that chewed pap after some standing, with cupric sulphate and caustic potash, at 70 C, yields red copper suboxyde. It does not change cane-sugar into invert sugar, and thus differs from yeast. The quantity of mixed saliva secreted by a man in 24 hours varies between 300 and 1500 grammes ; it may be greatly increased by excitants, and irritating medicines and poisons. sai^a in dia- Little is known of saliva in disease, but the investiga- tions of the future promise further results. In diseases, Anomalous , . . n ingredients, such as salivation under the innuence ot mercury, rhodanates disappear. The saliva then contains mercury. Many medicinal salts pass easily into the saliva from the blood, such as iodide and chlorate of potassium, and when used long in quantity produce slight salivation. In diabetes the saliva contains lactates, but no sugar. In the paralytic saliva of hysteric persons leucine has been found. Acid saliva seems to contain lactic acid, and is of course anomalous. The presence of urea has been alleged, but not proved with certainty. In hydrophobia the saliva is the bearer of the contact- poison by which the disease is propagated to other individuals. Digestion of While the saliva influences starch as indicated, and starch. does not lose its action by the admixture of acid of CHEMICAL PHYSIOLOGY. 7 the concentration of the gastric juice/it certainly, under ordinary circumstances, does not transform the whole of the starch into sugar. The gastric juice has no in- fluence on starch; the pancreatic juice a trifling influence in the same sense as saliva. Deducting all sugar and lactic acid to be met with, it is necessary to assume that other products are formed, which yet elude analysis. Do any of these products find their way into the liver, and are these transformed into glycogen ? G-lycogenis a kind of dextrine, which was discovered Sf nof in the liver by Bernard and Hensen. It occurs in three forms, of which one of the formula C 6 H 10 5 , is powdery, two others, C 6 H 12 6 , and C 6 H 14 7 , are gummy. It polarises to the right four times more intensely than dextrose sugar. "With a solution of iodine in iodide it gives a dark red colour. It dissolves copper oxyde without reducing it. By sulphuric and hydrochloric acids, saliva, pancreas juice, serum of blood, and cold prepared extract of liver, it is transformed into dextrine and ultimately into sugar. Many physiologists have endeavoured to explain the source and destination of this matter, but as yet without any very complete success. Regarding its origin, it has been found that it could not be formed from sugar, as the portal blood did not contain any. It was not formed from fats. Animal food enabled animals to form it, whence the conclusion was drawn that glycogen originated in albumen. Seeing that the liver decomposes albumen, as proved by the constitution of the bile, this idea has much in its favour, but the experiments upon which it is based admit of different interpretation. Muscle 8 CHEMICAL PHYSIOLOGY. frequently contains dextrine, always inosite (a particular kind of sugar), and lactic acid. All these might enable the liver of the animal which eats the flesh to form glycogen. At present it is uncertain from which material the liver forms glycogen ; possibly it is formed out of starchy and albuminous matters at the same time ; at least most of it is formed (up to 12 per cent, of the weight of the liver in fowls) when these two kinds of food are digested together in large quantity. As the dead liver was found to transform glycogen quickly into sugar, and as some sugar could be found in hepatic blood, it was concluded that glycogen is transformed into sugar, and passes into the blood, to be there oxydised or changed as required. This view, upon which was based an entire theory, called that of the glycogenetic function of the liver, was received for some years by physiologists in general, until one of its greatest admirers, Pavy, believed that he had discovered it to be erroneous. According to him no sugar is made in the liver in the living healthy body. I showed that his experiments admitted of such variation as to prove either his or Bernard's doctrine. At present the bulk of evidence goes to show that, as a portion only of the starch in the intestines is trans- formed into sugar and passes into the chyle, so a portion only of the glycogen of the liver is transformed into sugar and passes into the blood. Quantitative experiments on a large scale, combined with the chemolytic method of research, will alone be able finally to decide the matters under discussion. tfou"of 8 lSS" When sugar in considerable quantity exists in the CHEMICAL PHYSIOLOGY. 9 blood, the body cannot deal with it, and excretes the sugar unchanged. Such a condition constitutes the disease termed diabetes, which appears to be a much Diabetes - more complicated disease than its main symptom taken alone would seem to indicate. The oxydation of sugar only is diminished or not accomplished, that of the albuminous substance and fats is rather increased, sometimes enormously so ; therefore the carrying power of the blood- corpuscles for oxygen cannot be diminished as has been supposed lately, at least not in all cases of diabetes. There must be a perversion of chemical agency, as proved by the appearance of lactic acid in the saliva and of acetone in the stomach and the urine. On the whole there is at present neither a plausible theory nor a rational treatment of diabetes, as evidenced by the fact that noted physicians now maintain that diabetic patients eating promiscuously everything are better off than patients who abstain from starch and confine themselves to the anamylic diet so elaborately prescribed by Bouchardat. The sugar may be made in the liver or in the muscles, it may be the effect of a change of nervous influence (as suggested by the artificial diabetes of animals after wounds of the fourth ventricle of the brain), or of a failure in the supply of a ferment capable of transferring oxygen to it. The sugar when once in the diabetic blood appears not to be increased or decreased by standing of the drawn blood out of the body, the blood consequently contains perhaps no glycogen. This was ascertained by a special experiment, made upon the blood of a diabetic patient. 10 CHEMICAL PHYSIOLOGY. Se g fo S odTn?i f , e Tne comminuted food mixed with saliva arrives in the stomach and excites this organ to a mechanical and chemical action, termed digestion. The many- little rennet glands situated in the walls of the stomach Gastric juice, secrete a liquid termed the gastric juice, which in man contains 994*6 per mille of water and 5*39 of solid and permanently fluid ingredients other than water. Of these 3*0 are pepsine, 0*2 hydrochloric acid, with which perhaps a small quantity of lactic acid is mixed, and chlorides of the alkalies, with some phosphates of earths. Singular is the presence of some calcium- chloride in the juice. The juice has been examined mainly as obtained from persons who by accident had fistulous openings in their stomachs, and upon dogs upon whom such fistulas had been formed by operative interference. This led to the formation of artificial juice, which requires the addition of natural pepsine, and is therefore only in part artificial. It serves, however, for the purpose of studying stomach digestion upon many kinds of food, and of supplying a kind of remedy in diseased con- ditions in which the natural juice is supposed to be deficient. ic7ui?e gas " This gastric juice possesses the power of dissolving or reducing to a liquid state albuminous substances, which are either by preparation, such as boiling, or by nature, insoluble in water. Albumen, caseine, fibrine, syntonine, the albuminous substances of vegetables, gluten, and the collagene tissues or gristle, are under the influence of gastric juice, or of a mixture of pepsine and hydrochloric acid, dissolved to thickish CHEMICAL PHYSIOLOGY. 11 somewhat turbid matters, to which the name of peptones is given. Pepsine may be isolated by me- Peptone chanical precipitation in the same manner as ptyaline by adhesion to phosphate of lime. It is not itself destroyed during digestion, but is capable of trans- forming great quantities of solids into fluid by that mysterious influence termed contact action. When the juice is saturated with peptones it ceases to act, but an addition of dilute acid fluid enables digestion of newly introduced albuminous matters to be effected. The secretion of the hydrochloric (and lactic ?) acid from the stomach glands is a chemolytic process by which salts of alkalies are split up into acid and base. Of this action I shall show the completion of the circle in the biliary function immediately to be described. The origin of the pepsine is the blood, but which ingredient of this fluid yields this curious substance, which is so different from albumen, cannot be told. In the stomach digestion saliva by its ptyaline forms some sugar, the gastric juice fluidifies the albu- minous matters, the fats are made fluid and liberated from their tissue connections, vegetable structures are variously disintegrated, and the whole is mixed with water and a small amount of air carried down in the process of swallowing. Other decompositions, as yet imperfectly understood, also take place, as evi- denced by the strong odour of the digested matters, and at last the homogeneous mixture of substances, termed chyme, passes through the pylorus into the duodenum. The ingredients of chyme are starch, sugar, fat, chyme. and peptones, or if only animal food had been eaten, fat Peptones 12 CHEMICAL PHYSIOLOGY. and peptones alone. There are also undigested pieces of flesh, albumen, caseine, constantly present. It is at present impossible to say what these albuminous matters are. Some physiologists say there is only one substance, others that there are five and more, the statements as well as the experiments upon which they are based being quite irreconcileable with each other. None of these researches have as yet been carried out by means of the quantitative chemical method, excepting the comparison of the compo- sition of the peptones with the original matters. It was found to be almost unchanged. The pep- tone solutions are not coagulated by boiling, but are precipitated by absolute alcohol. They give Millon's reaction with nitrate and nitrite of mercury. They diffuse easily through parchment paper (dialyse) into water, exhibiting a property towards membranes of the utmost importance for absorption, which albumen possesses only in the very slightest degree. Optically they are characterised by turning the plane of polarisa- tion towards the left. The coagulation of milk in the stomach, or by rennet out of it, is supposed by some to be due not to pepsine, but to another ferment which transforms sugar of milk or lactose into lactic acid, and pre- cipitates the soda-albumen or caseine. This matter is problematical. The quantity of gastric juice secreted daily in the human stomach has been estimated at 10 per cent, of the body- weight, or 16 Ibs.; other direct observations, however, lead to 30 Ibs. CHEMICAL PHYSIOLOGY. 13 During digestion some gases, consisting of carbonic Gases. acid, hydrogen, and nitrogen, are not rarely formed from the digesting food. This may become a dis- tressing symptom in disease. Duodenal digestion is a continuation of stomach digestion under greatly complicated circumstances, since the chyme receives additions of bile and pancreatic juice. The physiology of these liquids has been studied upon fistulous openings occurring accidentally in man, or produced by art in animals. The secretory acts and influences are no doubt well known, particularly their variations under several conditions. But the employment of the secreted matters is by no means so elucidated as to be capable of satisfactory theoretical representation. The pancreatic juice has probably three functions, of which one is the completion of the 6 func " solution of the pieces of meat and albumen which issue from the stomach with the chyme ; another is the decomposition of fat into glycerine and fatty acid ; and a third the emulging of neutral fat, and the trans- forming of it into a subdivided condition, in which it may pass through the pores of the mucous membrane into the chyle-ducts. It also transforms a small quantity of starch into sugar. These properties are only possessed entire by juice which is abstracted from the pancreatic duct of an animal during full digestion, or from a reddened pancreas. Juice thus procured is tough or viscid, and contains 10 to 11 per cent, of solids, while juice obtained from a permanent fistula has only 5 per cent, of solids, and lacks the power of digesting albuminous fragments. It is probable that 14 CHEMICAL PHYSIOLOGY. this deficiency is caused by a degeneration of the gland consequent upon the operative interference. The juice contains an albuminous matter at present undefined, possibly some mucine, and generally leucine, which is present in the parenchyma of the gland in larger quanti- ties : it has a more or less alkaline reaction. Sf yfunc " ^ke liver has an obvious function, and that is to secrete bile. It seems almost superfluous to make such a statement, but the views of physiologists regarding this organ have so often been perverted that it is necessary to recur to elementary principles. The error regarding the function of the liver which has crept into physiology has mainly been caused by the discovery in it of a substance which has the capability of being transformed into sugar, namely, the above- described glycogen, also called hepatine, or liver- dextrine ; and in consequence of that in itself remark- able and interesting discovery it has generally been believed that the main function of the liver was that of forming sugar. We know now that such is not the case.* The main function of the liver is one of considerable intricacy, and essentially connected with the great features of the process of digestion. ?tom n a e c x hdi. of Digestion in the stomach is produced by a process fS S?e fiuic- in which of chemical ingredients hydrochloric acid tion. * See the articles of Pavy on this subject, ' Guy's Hosp. Rep./ 1858, iv, p. 291 ; ' Phil. Trans.,' 1860, p. 595, and my critical experiments in ' Brit. Med. Journ.,' vol. i, 1860. In these latter the analytical method now generally followed was first used and published ; it was afterwards adopted by Pavy, Bernard, Kiihne, and others. For confirmation of the variable results see Meissner, ' Jahresbericht fur,' 1862, p. 310 et seq. ; Bitter, ' Zeitschr. f , rat. Med./ 24, 65 ; Eulenburg, ' Journ. fur Pract. Chem./ 103, 108, 1868. CHEMICAL PHYSIOLOGY. 15 takes a main part. In the dog this hydrochloric acid is so strong that the hardest bones are absolutely dissolved. In man such a solution of bones cannot easily take place, but they are certainly corroded when introduced into the stomach. The acid which dissolves them in the dog is hydrochloric acid only ; in man it is probably a mixture of hydrochloric and lactic acid. But although we find in the economy chlorides everywhere, and lactates constantly in the chyle, yet we do not meet with these acids in the free state. We are therefore obliged to assume that in the walls of the stomach a chemical process is constantly taking place by which hydrochloric and lactic acids are formed. This process is very simple, consisting in the separation of the chlorine from sodium chloride (or common salt), and the combination with it of a certain quantity of hydrogen derived from the water. What takes place in the glands of the stomach may therefore be stated to be a splitting-up of water and sodium chloride, and a cross combination of the elements to hydrochloric acid on the one side and sodium hydroxyde on the other. H 2 + NaCl = HOI + NaHO -\ f -^ ( -^ f ^ Water. Common Salt. Hydrochloric acid. Sod. hydroxyde. The lactic acid is produced from lactates in a similar manner, and in the formula of its formation the place of chlorine in the foregoing formula would be occupied by the formula C 3 H 5 O 3 . This is simple and certain. But we find in the body no caustic soda, 16 CHEMICAL PHYSIOLOGY. or sodium hydroxyde, and we are therefore driven to inquire what becomes of it when so produced. Before it is carried away from the gastric glands by the blood, a part of this sodium hydroxyde has an important function to perform, namely, to protect the stomach against the corrosive action of its own secre- tion,* It keeps the blood and tissues more alkaline, and prevents the acids and pepsine, which have become more energetic after secretion and mixture with the peptones, from corroding the texture of the stomach. (Such corrosion immediately takes place in cases where the supply of blood to a part of the stomach is interrupted, or where food remains in the stomach undigested after the secretory energy has passed away ; gastric ulcer, hematemesis, chronic dyspepsia, or painful digestion with follicular erosion, and other pathological conditions, are produced in this way.) The sodium hydroxyde is soon transformed into carbonate in the blood, and passes through the gastric veins into the portal, and thus into the liver. When Bile - we analyse bile and add to it a quantity of acid, we precipitate certain matters, namely, the biliary acids formed by the liver, and the cholophaeine ; and if we evaporate the liquid we get a large quantity of sodium combined with the acid which we have added. Sup- posing now we take bile and add to it hydrochloric acid, we find at the conclusion of our experiment that sodium has been combining with chlorine and that we * This function was clearly developed and stated by me in ' Brit, and For. Med.-Chir. Review,' October, 1861, p. 429. At a later period it was made the theme of some interesting experimental inquiries by Pavy (' Phil. Trans.,' 1863). CHEMICAL PHYSIOLOGY. 17 have sodium chloride, and that the hydrogen of the acid has again combined with oxygen (hydroxyl) and formed water. NaHO + HOI = NaCI + H 2 O That is to say, by boiling bile with hydrochloric acid we reproduce the chloride of sodium which before has been decomposed in the walls of the stomach. In our food we take no salt of sodium combined with biliary acid, or any acid that can be transformed into it. We take many substances containing sulphur and nitrogen which can furnish the biliary or special organic part of the bile, but not the soda salts con- tained in it. Their production is just the function of the liver. The liver splits up or chemolyses albu- minous substances or albumen into products of which a part is at present unknown, another part, however, well known under the nsCme of biliary acids and coloured ingredients. They are taurocholic acid, glykocholic acid, cholophseine, bilifuscine, biliprasine, choline, lecithine, and cholesterine. Taurocholic acid (0 2a H 45 lf0 7 S) contains all the sulphur of the bile. By this ingredient it manifests itself as a derivate of albumen, which also contains sulphur. Glykocholic acid (C 26 H 43 N0 6 ) is nitrogenous only, and free from sulphur. Both acids yield by chemylosis an acid free from nitrogen and sulphur, cholic acid (C 24 H 40 5 ). But the sulphuretted acid yields as the second product a body containing all the sulphur and nitrogen of the original acid, namely, taurine= C 3 H 7 ]Sr0 3 S = dehydrated isaethionate of ammonia, and 2 18 CHEMICAL PHYSIOLOGY. producible from such ; while the other compound acid yields as the second product of its cleavage glykokoll or amido-acetic acid (C 3 H 5 N0 3 ), which is producible artificially by various processes. The rational con- stitution of the smaller nuclei is thus shown to be well known ; but the same could not be said of cholic acid. Glykokoll appears in an excretion as hippuric acid (in which it is coupled with benzoic) but it is at present uncertain whether this excreted glykokoll has previously taken any share in the composition of bile or not. Taurine, however, is consumed in the body, and its sulphur appears in the excretion as sulphuric acid. The coloured ingredients of bile are cholophaeine or bilirubine, C 9 H 9 N0 3 , and bilifuscine, probably C 9 H 11 N0 3 . By oxydation and loss of carbonic acid cholophasine easily passes into biliverdine, C 8 H 9 N0 3 , according to the formula, C 9 H 9 N0 2 + 20 = C 8 H 9 lSr0 3 + C0 2 . Cholesterine (C^H^O) occurring in the brain and blood is no doubt excreted by means of the bile. It is a polydynamic alcohol, capable of forming ethers analogous to fats. Coloured matters, such as cholo- nematine, boviprasine, fuscopittine, muscoprasine, and ethochlorine, all possessing characteristic pro- perties and spectra, and cholesterine are the main residues of certain diseased processes which terminate in the production of calculi. In a degeneration of the liver, called bacony, considerable quantities of chole- sterine remain stagnant in the parenchyma of that organ. The choline of the bile is an organic base of CHEMICAL PHYSIOLOGY. 19 the composition 5 H 15 N0 2 . It is closely related to neurine, C 5 H 13 N, a base obtainable, together with choline, from cerebric acid or lecithine, and we are justified in assuming that it is derived from the de- composition of that body. Lecithine consequently may be considered as a normal ingredient of bile. The biliary acids yield a particular test, called, after its discoverer, Pettenkofer's reaction. When mixed with sugar and sulphuric acid they produce a splendid purple colour. It has been found that other acids, such as lithofellic, also yield this test ; and I found, further, that cerebric acid yielded it with rare in- tensity. I therefore applied the spectroscope, and was glad to discover some means for the distinction of the various acids in the coloured test solution. The biliary acids show two bands, cerebric acid and vitelline only one. These spectra are, however, difficult to observe, and require sunlight or oxhydrogen light for their complete development. The quantity of bile secreted in the human body in a day has been estimated at 1200 grammes, or the bulk which would fill a wine bottle and a half. Con- clusions from quantities observed in animals can only be used with caution, as some animals, e. g., the guinea- pig, produce enormous quantities of bile relatively to their body weight, while dogs and sheep produce relatively small quantities. The production is more likely to stand in proportion to the size and weight of the liver (hitherto neglected as a physiological factor) than to the weight of the body, to which hitherto quantities were almost exclusively referred. 20 CHEMICAL PHYSIOLOGY. The biie inthe The function of the bile is evidently like its chemical intestine. constitution, very complicated. Stored during inter- vals between digestion, it is mainly secreted as well as expelled from the gall bladder during digestion, and a particular quantity of it during a peculiar episode at the end of the emptying of the stomach. On being mixed with the acid of the chyme, the biliary acids are set free, but not precipitated, as the soluble taurocholic acid holds the glykocholic in solution. But a pre- cipitate of peptones is nevertheless produced in the ?ones fpep ~ mixture of chyme and bile. This, mixed with the bile- acids and the biliary colouring matter, passes along the intestine as a resinous adhesive substance, to be altered and made absorbable by the many influences of intestinal reaction. It is soluble in alkali, and as much of the intestinal secretion besides gastric juice is alkaline, the transformation meets with no difficulty. The peptone then may pass into blood and chyle as albumen and fibrinogen and nbrinoplastic matter, but the bile is not so easily accounted for. The acids biiT ges ( certainly split up, taurine and glykokoll returning into the circulation, but the cholic acid mainly disappears, without leaving any trace in the blood or chyle; neither contain a trace of biliary matter. In the faeces only occurs a small proportion of the cholic acid, amounting in man to from two to three grammes, being perhaps one eighth or one twelfth of the entire amount secreted. The cholophaeine has been also changed and become insoluble in chloroform. We must therefore assume that the cholic acid is already split up or chemolysed in the intestine, and reaches CHEMICAL PHYSIOLOGY. 21 the circulation in the more simple form of products of its decomposition. The bile influences fats and fatty- acids in the manner of a soap. It communicates to the small absorbing tubes an attraction for fat, so that capillarity raises the fat to a higher point than the same vessel would do without bile. Bile then re- presents the accomplishment of a purpose which we term chemolysis of albumen. But the further uses of bile are numerous and important ; the excretion of cholesterine, intimately related to the chemistry of the nerves, and possibly a product of their action; the excretion of choline and probably lecithine, of which the objects are continuous ; the excretion of cholophgeine, eases. 11 of which the objects are at least obscure. Bile pre- cipitates pepsine, and when it regurgitates into the stomach arrests digestion completely. It therefore puts an end to pepsine digestion in the duodenum, and favours the alkaline pancreas-digestion. In disease the bile may be retained and cause jaundice, and slowness of the pulse ; or it may be decomposed in a peculiar mannner and produce concretions ; in man these consist of cholesterine and modified bile-acid, and bilifuscine, with cholophaBine and earths ; in oxen the cholophasinate of lime predominates, and modified bile-acids with lime-soaps are in lesser quantity. In pigs these calculi contain a peculiar lime salt which assumes a voluminous crystalline form, when the powder is digested with cold alcohol. The pancreas ?** has in diseases been observed to be degenerated and cancerous ; and as in these cases lumps of fat are stated to have been observed in the fasces, this ap- 22 CHEMICAL PHYSIOLOGY. pearance of fat has been ascribed to the failure in the supply of pancreas-juice. In lientery the pancreas as well as the stomach and pylorus is probably at fault. ^e digestion in the small intestine is very imper- fectly known, and requires particular and great re- searches in the future. In this part of the body is the constant and principal seat of diseased processes of the greatest importance, e. g. 9 typhus and typhoid fever, cholera, and others, not the least important amongst them the aestival and autumnal diarrhoea so fatal to many persons in every year without special epidemic influences. human f and Glycerine is a tridynamic alcohol, constructed ac- body ' cording to the type of water thrice condensed. In this type there are six atoms of hydrogen replaceable ; when three of these are replaced by the tridynamic radical glyceryl, glycerine is formed. Glycerine, therefore, has three atoms of typical hydrogen, which can be replaced by three atoms of a mono- dynamic body or one atom of a tridynamic body. It is not necessary to substitute all the hydrogen at once when we work synthetically, but in animal bodies all the hydrogen is always replaced by fatty acids. A fat is thus shown to be a body of the type of three atoms of water condensed to one, thus in which three atoms of hydrogen are replaced by one atom of glyceryl 111 and three others by three atoms of CHEMICAL PHYSIOLOGY. 23 fatty acid radical. 1 Tributyrine, a fat occurring in butter, has this formula : 3 monodynamic atoms of butyryl = (C^H^O) 1 (C 4 H 7 0)< L 1 tridynamic atom of glyceryl = (C 3 H 5 ) ni ^ held together by three didynamic atoms of typical oxygen. The Roman numeral to the right of the radical buty- ryl signifies that it is a monodynamic radical, and can replace only one atom of hydrogen ; but the Roman numeral to the right of glyceryl shows it to be a tri- dynamic radical, which by its one atom replaces three atoms of hydrogen. The other fats occurring in the human body and in animal food are tripalmitine 3(C 16 H 81 0) (C 3 H 6 )'" which is equal to the large formula of jo, tristearine, a fat abounding in mutton and beef, of the formula CsyHnoOg and trieleine, a more fluid fat, which abounds in the oils extracted from lower animals and vegetable seeds. Yellow animal fats contain luteine, a yellow coloured substance showing peculiar absorption phenomena (three bands) in the blue part of the solar spectrum. When these fats have passed through the stomach, 24 CHEMICAL PHYSIOLOGY. and after solution of all tissue by which they are held together in the parts of animals, arrive as fluid oils in the intestine, they are acted upon by the pancreatic juice and the bile. The former affects them in two ways. A small portion it decomposes, so that glycerine and fatty acid are formed, another portion it emulges, or makes fit to become subdivided into the very minu- test mechanical molecules, and in that state to pass through the small pores of the cylindric cells which cover the villi of the intestine. The fatty acids mostly combine with soda and pass as soaps into the venous blood, and with this to the liver ; while the emulged neutral fats pass into the lymphducts, and by them into the venous blood, without passing through the liver. After incorporation with the blood the fat is burned up in the system, particularly the muscles. emuff'of -^ u ^ ^ nere i g y e ^ a particular form in which fatty pXitic nd acid is found in the body, namely, emulged in phos- phate of sodium solution. When palmitic or stearic acid is boiled with common sodium phosphate, it forms a milky fluid ; the acid is so finely subdivided that the microscope can distinguish only the very finest mole- cules. When this process is applied to neutral fats, , or to oleic acid, no effect is produced. The emulsion is a very loose combination, inasmuch as ether extracts the fatty acids. This particular form of fatty acid emulsion occurs in lipohsemia, or fatty blood disease, in chylous urine, and in several effusions into internal cavities.* Its formation is a normal occurrence, the phosphate of sodium of the food (bread) yielding the * Compare on this subject my researches published in the ' Lancet.' CHEMICAL PHYSIOLOGY. 25 mineral ingredients for the carrying on of the process with the digested fat in the intestinal canal; if the phosphate be wanting in the food, the bile which always contains notable quantities, will supply it [and it is to this action of the phosphate in bile that any influence upon fatty acids which it possesses is due, the action upon neutral fats formerly ascribed to it being an erroneous conception]. The anomaly in the above- mentioned diseases is the persistence of the fatty emulsion in the arterial blood, whereby an obstruction of the circulation and consequent effusion (of blood, serum, fatty and fibrinous serum, as in apoplexy, dropsy, chylous urine, and other diseases) is produced. Fat having been frequently found in degenerating tissues, deposited in a visible manner, in parts where healthy structure shows no visible fat, microscopic anatomists admitted a particular fatty degeneration, in which fat in excess assumed the place of albuminous matters. The heart was supposed to be particularly subject to this disease, to which, however, all other tissues paid tribute. This doctrine, however, is at pre- sent in a very unsatisfactory state, and requires much elucidation by researches conducted upon mathematical principles. That fatty degeneration so called may be a very complicated chemical disorder, I showed many years ago by the demonstration of changes in the myochrome of the muscles of the heart, which produced a green granular pigment.* Chyle is the fluid which the lymphatic vessels of the cn y ie * See ' Trans, of the Path. Soc.,' vol. vi, 1856, p. 141, and ' Quart. Mic. Journ.,' vol. iv, 1856, p. 111. 26 CHEMICAL PHYSIOLOGY. villi of the intestine absorb from the digested food and carry to the blood. It contains much fat, to which it owes its white milky appearance. It further contains the ingredients for the formation of fibrine, and curdles soon after it is withdrawn from circulation. Then there is potassium-albumen, and the ordinary albumen of serum. There are also lactates, sugar, and urea contained in chyle, besides a certain amount of alkaline salts. Chyle is the material by means of which the blood is constantly renewed. It contains mostly some white and red blood-corpuscles, which leads to the idea that they might perhaps be formed in certain lymphatic glands through which the chyle has to pass. Before entering the blood, chyle is always mixed with a con- siderable quantity of lymph, which differs from chyle only by the absence of fat in emulsion. The lymph is transuded serum of the blood, which penetrates into the tissues and there performs its functions ; it is then reabsorbed and carried back to the circulation by the lymphatic vessels. There are many derangements of the lymph and chyle which occur simultaneously with diseased glands in scrophula, and in tuberculosis, and it is probable that improper nutrition has the main share in the production of these derangements in a great number of young children. ^ke peculiar shape of the blood corpuscles appears biooJf-cof- to be partly dependent upon their chemical constitution. This latter is the product of their own powers and their interchange with those of the surrounding serum. They have a certain specific gravity, which is main- tained or varied (in diseases, in different classes of CHEMICAL PHYSIOLOGY. 27 animals) by the quantity of certain chemical ingredients which are within them. Amongst these latter most notable by its red colour, and in the first place by its chemical constitution, is hematocrystalline.* This sub- stance contains carbon, hydrogen, nitrogen, iron, sul- -, -, . .'._._ phur, and oxygen, in the proportions indicated by the following formula : C 600 H 960 N 154 FeS 3 177 . This leads to an atomic weight of 13,280, or if it be deter- mined by the quantity of that most stable element, iron, an atomic weight of about 13,000. Persons who have not studied this branch of chemistry, and who perhaps in their handbook, do not read of atomic weights rising above 500, may wonder at the high atomic weight here assigned to hematocrystalline. But this body can now be obtained pure in quantity, and the analyses of crystals have always shown them to contain four tenths per cent, of iron. The crystals are mostly of the rhombohedric system, and appear in tetrahedra, octahedra, with and without prisms, or in prisms only. Their watery properly diluted solution, when examined in the spectroscope, shows two remarkable bands of absorption, and obscu- ration [of the blue and violet end of the spectrum. As the blood of all vertebrate animals, when viewed When the blood crystals were first discovered, and their various shapes and properties found out (Funke, Kunde), it was believed and stated (Lehmann) that they consisted of a colourless substance (hema- toglobuline) to which a coloured matter (hematine) adhered like a dye. As long as the researches on this subject moved on the microscopic field only, this idea was plausible ; for many crystals are actually so thin as .to appear colourless under the microscope. But the chemical and spectroscopical researches of the last few years have established the error of this conception and substituted the doctrine of the text. 28 CHEMICAL PHYSIOLOGY. within the living blood vessels, shows the same bands, we can assume that hematocrystalline is present in it as such, and not formed by the process of preparing the crystals. Hematocrystalline can be deprived of its oxygen, and then its spectrum changes to that of reduced hematocrystalline. Shaking with oxygen, restores the double-banded spectrum. The two bands up into albu- therefore belong to arterial blood, the one band to venous blood (Stokes). Hematocrystalline contains as proximate constituents an albuminous body, which after separation remains amorphous and colourless, and hematine, which retains the colouring power, the spectral influence upon light, and the iron of the original substance, though all varied in kind, proportion and quantity. Hematine has an atomic weight of about 620, and from 7*5 to 8 per cent, of iron. It occurs together with hematocrystalline in the urine in cruenturesis (paroxysmal hematuria). It yields many remarkable products of decomposition. Its spectra in various solvents and in the reduced state, and the spectra of the new derivates, are very charac- teristic. The optical and chemical phenomena of hematocrystalline and hematine are applicable to medico -legal research, as affording the most certain diagnosis of blood upon the smallest quantities of material. A diminution of hematocrystalline in the body constitutes the disease termed " chlorosis" or " anaemia." It is either a specific ailment, or a sym- ptom and consequence of chronic disorders, or acute, particularly tropical fevers. Tiood C -co C r- d Besides hematocrystalline the blood corpuscles con- puscles. CHEMICAL PHYSIOLOGY. 29 tain a quantity of cerebric acid or of lecithine. This has been variously called myeline (Virchow), protagon (Liebreich), and other names, but it is probably the same body as that which can be extracted from the brain. We further have in blood corpuscles a certain quantity of st what is called stroma. This is merely a name for a substance which is supposed to give them a shape. The stroma remains when the other bodies are extracted. It is a kind of chemical skeleton, and can be isolated (by freezing, for example) and investi- gated (Rollet). It seems to be very different from the albuminous matters combined in hematocrystalline, for it is soluble in ether, alcohol, and chloroform, when these agents are dissolved in serum. But it contains a small quantity of fibrino -plastic substance (Alex. Schmidt), namely paraglobuhne, sometimes also termed stroma con- globuline. This remains insoluble when the blood- buline> corpuscles, previously separated from serum by solu- tions of salt, are deprived of hematocrystalline by water. The gelatinous paraglobuline, after shaking with water and ether, is soluble in solutions of salt, dilute alkalies, and water containing one per mille of hydrochloric acid. Brought in contact with fibrino- genous solutions it frequently produces fibrine. The blood-corpuscles carry oxygen, which has great J]*faj