aps/-^'i Columbia ©nitJCi^ttp mtl)fCitpofi^ruig0rk COLLEGE OF PHYSICIANS AND SURGEONS LIBRARY (% ./^ ANIMAL CHEMISTEY LOSDOS : PRINTED BY EPOTTISWOODE ASD CO., SEW-STRKET SQCAaS ASD PAKLIAJIEST STREET ANIMAL CHEMIBTEY OB THE EELATIONS OF CHEMISTEY TO PHYSIOLOGY AND PATHOLOGY A MANUAL for MEDICAL MEN and SCIENTIFIC CHEMISTS CHAELES THOMAS KINGZETT, F.C.S. Member of Council of the Institute of Chfmistry of Great Britain and Ireland Author of ' History, Products, and Processes of the Alkali Trade ' &c. LONDON LONGMANS, GEEEN, AND CO. 1878 All rights reserved TO THE EEV. E. CAPEL CUEE, M.A. RECTOR OF ST. GEORGE, HANOVER SQUARE WHOSE KINDNESS AND GOODNESS ARE AMONG THE AUTHOR'S BRIGHTEST MEMORIES OP HIS CHILDHOOD S^l^is Wioxk is Insmbir IN AFFECTION AND GRATITUDE Digitized by tine Internet Arcliive in 2010 witli funding from Open Knowledge Commons (for the Medical Heritage Library project) http://www.archive.org/details/animalchemistryoOOking PEEFACE. For four tears I was occupied with the practical study of subjects comprehended in the following chapters, and during the whole of that time there were no fluctuations in the success attending the labours in which my services were involved. The field of research was a compara- tively new one, and in whatever direction the methods of science were applied, results of no doubtftd mean- ing were obtained. Simultaneously with these discoveries greater fields for research came to view ; so quickly, in- deed, that at every point the hand failed to keep time with the mind. It was therefore a matter of sincere regret with me that circumstances (which are said to be stronger than men) ultimately necessitated the discontinu- ance of my connection with work which had given me so much real pleasure. Pleasure is a different thing to different men. The poet, in contemplating the harmony of nature which he perceives beneath its rugged heterogeneity, and to whom every blossom and every bough shaken with the wind conveys a sense of the beautiful or the wild, finds his VIU PREFACE. gi'eatest pleasure in his own thoughts. So again, the artist gazing upon his handiwork; lost in the wonder- work of his skill, the lines of beauty ^v^ought by his hand, he sees therein the expression of his own fancy, and his cunning is pleasure to him. The scientist knows also his own pleasure. For if the poet, listening to the surge of seas, may hve over again an age that is buried, or may be reminded of another sound which was once dear to his heart, so surely the scientist may prolong his intellectual sight into the future wdth a corresponding emotion. As the excitation of a memory may hold the hand and the heart spell-bound, so the anticipation of a coming event may be a cause of equal pleasure, and with the scientist such anticipations, composed as they often are half of logical inference and half of intuitive assumption, are not of rare occurrence. The scientist is a greater philosopher than the senti- mentalist, for while the latter pays his addresses to heterogeneous nature as a whole, the former condescends to details, decomposing and reconstructing; and the in- nate perception of harmony lodged in the brain of the poet, becomes at the hands of the scientist an established law abidinsf with mathematical exactitude. Given a line of inductive reasoning based upon ex- perimental data, and its proper pursuit must lead sooner or later, rarely or more often, to discovery. The dis- covery may be of a substance, of a law, or better still, a generalisation ; and the imagination, ever quicker than PEEFACE. IX the hand, traces out the interworkings and connections of the discovery, perpetuating its effect into the future. But the attendant pleasure is reasonable, and may be alluded to without conceit. It was natural, then, that having experienced so much pleasure, I should be moved with equal regret in re- signing the practical study of physiological chemistry ; and in order to complete a well-remembered but brief connection with this subject, I determined to attempt a task which should prove of service to scientific men, namely, to collect and systematise, as far as could be, all the trustworthy work on record in relation to Animal Chemistry, so far as it concerns the human body. The task has proved heavy, because the hterature that had to be waded through was so enormous and was scattered broadcast. Moreover, the sifting of the good work from the bad was equally exhaustive. However, I have tried to do my work faithfully and to the best of my ability, and if I have wronged any investigator it has been done unconsciously. I may explain that it has not been my object to col- late every fact which may fairly be included in the sub- ject of physiological chemistry, nor to detail well-known methods of analysis, but rather to present, in as natural an order as possible, all those parts of the subject which, when properly arranged, present something like a system. In doing this, the various methods of research have been particularly described, and even researches published up to date have been included : further, I have endeavoured X PREFACE. to comprehend in the sclieme of the work, every known subject having a direct relation with the objects of Animal Chemistry. The proper understanding of the book will depend to a large extent upon the reader's knowledge of chemistry ; but this is inevitable ; and as pure chemistry is taught to some extent in our medical schools, and so well treated in many excellent text-books, I have not thought it necessary to enter into the subject except in an incidental manner here and there. I have availed myself freely of all existing treatises upon the subject of this work, and have given full references. In conclusion, I earnestly hope (as I also believe) that scientific chemists will find the volume useful as a guide to them in their researches ; and with this thought before me, I have given a category of subjects calling for further investigation at their hands ; while for medical men my object has been to present them with a comprehensive account of the most important subject included in their studies and profession. Charles T. Kingzett. 12 AxjRioL Road, The Cedars Estate, West Kensington, London, W. CONTENTS. PAET I. GENERAL. CHAPTEE I. INTEODUCTOBY, PAGE Boerliaave founds Organic Oliemistry — Other Early Labours in Physio- logy and its Chemistry — Discovery of Animal Electricity — Sjnithesis of Urea — Liebig establishes a New Method in Chemistry — Teach- ings of Liebig and of Mill — How Science progresses — Nature of Vital Force — Animal Chemistry; its Object and Pursuit — How Animal Chemistry is taught^ — The Republic of Science ... 3 CHAPTER II. LIFE : FROM A CHEMICAL POINT OF VIEW. Man is a Conscious Machine — Definition of the Human Body — Resume of Processes occurring in the Body — The share of Chemism in Life — Future Revelations of the Nature of Life Processes . . .18 CHAPTEE III. CHEMISTRY AS APPLIED TO PHYSIOLOGY AND PATHOLOGY. What Chemistry can teach about Life — Animal Chemistry concerns itself with Dynamics — The Structure Theory of Chemistry is not of primary importance to Animal Chemistry — Chemical Principles and Educts of the Body classified— Classification and Description of large Groups of Substances — Chemical Changes occurring in the Body, such as Hydration, Oxidation, &c. — Analytical, Synthetical, and Escretory Powers of Life ....... 25 xn CONTENTS. PAET II. ORGANS, FLUIDS, AND PROCESSES CONCERNED IN DIGESTION, ETC. CHAPTER IV. SALIVA, AXD ORAL DIGESTION. PAGE Mixed Saliva ; its Constituents and their Function — Chordal Saliva — Sympathetic Saliva — Ganglionic Saliva — Paralytic Saliva — Parotid Saliva — Saliva in Disease 47 CHAPTER V. GASTRIC JUICE AND GASTRIC DIGESTION. Resum^ of Gastric Digestion — Description and Characters of Gastric Juice — Analyses of Gastric Juice — Function of Gastric Jiuce — Nature of Pepsin — The Acid of Gastric Juice — The Function of this Acid — General Characters of Chyme and Peptones — Further Observations upon Pepsin — Abnormal Constituents of Gastric Juice 55 CHAPTER VI. THE BILE ; PANCREVTIC, INTESTINAL, AND SPLENETIC JUICES ; INTESTINAL DIGESTION, AND F^CES. General Characters of Bile — Analysis of Bile — Quantity and Composi- tion of BUe — The Ash of Bile — Biliary Concretions — The Pancreas — Pancreatic Juice and its Function — Intestinal Juice and its Func- tion — The Spleen and its Juice — Intestinal Digestion — Fteces and their Composition — Chemistry of Particular Constituents of Fasces — Faeces in Disease 65 CHAPTER VII. CHEMISTRY OF THE BILE. Glycocholic Acid — Taurocholic Acid — Cholic Acid — Choloidic Acid — Dvslysin — Some Generalisations — Glycocine — Taurine — Cholesteriue —Bilirubin — Bilifuscin— Other Biliary Pigments — Other Consti- tuents of Bile 84 CONTENTS. XIU CHAPTER VIII. THE LIVER ; ITS FUNCTIONS. GLYCOSURIA AND DIABETES. PAGE Description of the Liver — Its Constituents — Its Diseases — Function of the Liver — The Secretion of Bile — Liver Dextiine or Glycogen — Elaboration of Glycogen, and its Destiny — EoUo's Explanation of Diabetes — The Treatment of Diabetes — Researches on Diabetes — The Production of Glycosuria — Pavy's Researches on Glycosuria — Critical Remarks on various Researches — The Brain in Diabetes . 107 PAET III. NUTRITION; OR ' WORK AND WASTE: CHAPTER IX. CHYLE, LYMPH, AND BLOOD. Chyle is the Digested Fluid absorbed by the Lymphatics — Absorption of Chyle — Analyses of Chyle — Chyle as it en'ers the Blood — Lymph and its Characters — Blood — General Characters of Blood — Constituents of Blood — Amount of Blood — Composition of Blood — Serum and the Corpuscles — Cruor or Crassamentum — The Sugar present in Blood — Bernard's and Pavy's Researches on the Amount of Sugar in Blood — Blood Corpuscles and their Chemical Constitution — ^Heemato-crystalline — Hemiue — Paquehn and Jolly's Researches on the Colouring Matter of Blood — Thudichum and Kingzett's Researches — Hematine — ^^he Phosphorised Principle present in Blood Corpuscles — Supposed Relations between the Colouring Matters of Blood, Bile, and Urine — The Coagulation of Blood — The Natural Formation of Fibrin — Recent Researches on Coagula- tion — The Albuminous Principles contained in Blood — The Blood in Disease 123 CHAPTER X. NUTRITION OR ALIMENTATION. The sustaining of Body Weight — Matters removed from the Body — Food and its Pm-poses — The Necessity for taking Food — What becomes of Food — The Amount of Food required — Dietary Values XIV CONTENTS. TAGE of different Foods — The Animal Heat generated by Combustion of Food within the Body, and its Equivalent in Power— Relative amounts of Air inspired under varying Degrees of Exertion — The amount of Carbonic Acid evolved— Tlie Advisability of taking a Mixed Diet — Tables showing tlie Nutritive Values of Foods — Bio- plasm— Observations on Physiological Combustion . . . .151 CHAPTER XI. UESPIRATIOX, BREATH AND MUSCLE OXIDATION. The Blood conveys Nourishment to all Parts of the Body— Spectro- scopic Characters of Blood — The State in which Oxygen exists in Blood — The Corpuscles carry Oxygen — Carbonates in the Blood — Mill's Predictions about Respiration — The Oxidising Power of Blood— The Amount of Oxygen contained in Blood — Diffusion in the Lung Membrane — The expired Air and its Composition — Smith and others on Respiration — Food and Excreta compared — The Muscles store Oxygen in their Tissue — Poisonous Action of com- pressed Air or Oxygen — The Relation between the Supply of Oxygen and the Excretion of Urea — Further Observations on Physio- logical Combustion . • . 1G5 CHAPTER XII. ANIMAL HEAT, VITAL FORCE, AND MUSCULAR ACTION. Temperature of the Breath — The Mean Animal Heat— How Animal Heat is maintained— Clothing — Heat of Combustion — The Muscle transforms Force— Oxidation in the Lesser Circulation is the Source of all Muscular and Vital Force— The Metamorphosis of Force — The Electric Nature of the Force generated in the Blood — Force is stored in the Brain, and is transmitted from this Centre, being variouslv transformed according to the Nature of the Media through which it is manifested— The Nature of the Mind — The Dj-namics of Muscular Force 177 CHAPTER XIII. THE URINE AND ITS CHEMISTR?. The Blood which supplies the Kidneys— The Blood which leaves the Kidneys — The Secretion of Urine— General Characters of Urine — Average Amount of Urine — Average Composition of Urine — Urea —Uric Acid and its Constitution — Xanthine — Hypoxanthine — CONTENTS. XV PAGE Guanine — Kreatine— Kreatinine — Sarkosine — Hippuric Acid — Ee- ducine — Indigogen and Urrhodrtiogen — Indigo Blue — Pyrocatechin — Phenol and Oresol-producing Substances — Tlie Colouring Matters of Urine — Urerythrine — Urrhsematine — Uroclirome and its Decom- position Products — Kryptophanic Acid — Inorganic Constituents of Urine — Other Matters occurring in Urine — Urinary Sediments and Calculi — Other Morbid Conditions of the Urine .... 185 CHAPTER XIY. SWEAT. Sudoriparous Glands — Sensible and Insensible Perspiration — Amount of Sweat — Amounts of Water and Carbonic Anhydride exhaled by the Skin — The Constituents of Sweat — Analysis of Sweat — Sweat in Disease 256 PAET IV. OTHER ORGANS, TISSUES, AND FLUIDS OF THE BODY. CHAPTER XY. THE CHEMICAL CONSTITUTION OF THE BRAIN. The Literature of Brain Chemistry — Hensing discovers Phosphorus in the Brain — Spielmann examines Brain Ash — Monch obtains Oxalic Acid — Gurman on the Conservation of Brains — Burrhus compares the Brain to an Oil — Thouret considers it to be a Soap — Fourcroy obtains various Principles in an Impure State — Vauquelin makes a Great Advance — John confirms his Observations — Gmelin works on Cholesterine — Kiihn obtains a New Principle — Lassaigne analyses the Retina and Optic Nerve — Couerbe discovers Cephalote and is led to brilliant Results — Fremy criticises the Work of Couerbe — Chevreul on Fats — Gobley's researches on Eggs — Gobley's re- searches on Brain Matter— Liebig on Extractives — Bibra analyses impure Cerebrine — Miiller obtains pure Cerebrine, and examines the Extractives — Stadeler and Frerichs find Leucine — Liebreich's Work on Protagon and Neurine — Koehler recognises Hypoxanthine and Tnosite. and makes Observations on the Phosphorised Principles — XVI CONTENTS. PAGE Otto works with Cerebrine, and obtains Sugar — Diakonow studies Lecithine — Strecker's Research on Eggs : Lecithine — Baeyer works on Xeurine — A. W. Hoffmann on Ammonium Ba^s — Von Babo and Huschbrmiu discover Sinkaline — Petrowsky fails to advance Brain Chemistry — Gobley's Analysis of Brain Substance — Jaksch finds Nuclein in the Brain — Selmi experiments upon Braiu Putrefaction — How Brain Chemistry is treated in Modern Treatises — The Re- searches of Thudichum — The Water present in Brain Substance — Extraction of the Brain Principles — Separation of Brain Consti- tuents — Diagrams showing how to isolate the different Principles of Brain Substance — The Albuminoid Principles — The Phosphorised Principles — Thudichum and Eingzett on Glycerophosphoric Acid — Kephaline — Myelines — Lecithine — Glycerophosphoric Acid and its Salts — Xeurine and allied Bases — Critical Notes by Kingzett — The- Cerebrine Group of Substances, including Cerebrine, Phrenosine, and Kerasine — Cholesterine — The "Water Extracts — The Inorganic Principles — Copper in the Brain and other Tissues — Kingzett and Paul on the Physiological Action of Cupric Sulphate — The Physio- logy and Pathology of the Brain — Intercrauial Pressure — Brain Poisonir.g — Softening of the Brain — Delirium. Tremens — Percy, Marcet, Thudichum, Dupr^,Anstie,&c., on the Physiological Action of Alcohol — Kingzett on the Action of Alcohol on the Brain — The Brain in Typhus and other Diseases — Tumours in the Brain — Locomotor Ataxia — Chemical Examination of Diseased Brains • li63 CHAPTER XVI. OTHER AXIMAL ORGANS, TISSUES, AXD SOLIDS. The Thymus Gland — The Thyroid Gland — The Supra-Renal Corpuscles — The Ovaries — Muscular Tissue and Extract of Meat — Syntonin — Myochrome — Rigor Mortis — The Muscles in Disease — Inosic Acid — The Bones — Analyses of Bones — Bone considered to be a Che- mical Individual — Induced Modifications in Composition of Bones — Bones in Disease — Teeth — Analyses of Teeth — The Nails — The Hair — Haii* standing on End — Analysis of Hair — The Colour of the Hair — Pigmentum Nigrum — Cartilage — Connective and Elastic Tissue — Mucin — Ear "Wax or Cerumen 324 CONTENTS. XVll CHAPTER XVII. OTHER FLUIDS OF AJSTIMAL ORIGIN. PAGE JNIilk — Oream — Butter — Milk Sugar — Kouniis — Casein — Analyses of IVIilk — Colostrum — Seminal Fluid — Spermatozoa — Mucus — Nasal Mucus — Liquor Amuii — Allantoic Fluid — AllantoLn — Synovia — The Tears — Pus — Pyin — Antiseptic Treatment of Wounds — Pus in Disease — Pyocyanin 345 PAET V. CHEMICAL AND PHILOSOPHICAL SUBJECTS. CHAPTER XVIII. ALBUMINOUS PRINCIPLES, INCLUDING PEPSIN AND PEPTONES. General Description of Albuminoids — Nuclein — Criticism by Kiugzett and Hake — Different Sorts of Albuminous Matters — The Synthesis of Albuminoids — All Albuminoids are derived from a Common Type — The Hydration of Albuminoids — Schiitzenberger's Researches — Fibroin and Seracin — Cyanogen Compounds of Albumin — The Constitution of Albuminoids — The Oxidation of Albuminoids — The Bromination of Albumin — Indol from Albumin — Putrefaction of Albuminoids — Combinations of xAlbuminoids with Different Salts — Basic Compounds of Albumin — Acid Compoimds of Albumin — Analyses of Different Albuminoids — Gelatigenous Principles — General Properties of Albuminoids — Notes on Individual Albumi- noids — Seralbumin — Ovalbumin — Paralbumin — Metalbumin — Para- globulin — Globulin — Myosin — Vitellin — Acid Albmnin — Alkali- Albumins, or Albuminates — Casein — Legumin — Fibrin — Lardacein — Gelatin — Chondrin — Sericin and Fibroin — Elasticin — Keratin — Mucin — Pyin — Solubilities of Albuminoids — Pepsin and its Func- tion — Its Influence is like that of Acids — Imperfect Pesearches on Peptones — Criticism of Kingzett and Hake — Formulse of Peptones — Digestion of Ox Fibrin — Action of the Pancreatic Ferment — Pepsin and Pancreatin exercise a Hydrating Influence on Albumi- noids — Leucine and Tyrosine as produced from Albuminoids — Con- stitution of Leucine and Tyrosine — Oxidation of Leucine, Tyrosine, and Glycociue in the Organism — Preparation of Leucine and Tyro- sine — Pmification, Properties, and Decompositions of Leucine — Purification, Properties, and Decompositions of Tyrosine . . 359 a xvm CONTENTS. CHAPTER XIX. CHEMISTRY OF ANIMAL CARBOHYDRATES. PAGB General Account of Carbohydrates — The Constitution of Sugars — Phenose — Hexhydric Alcohols — Cai'bohydrates may be divided into Glucoses, Saccharoses, and Starches — Pi-incipal Reactions of dif- ferent Carbohydrates — Constitution of Starches .... 401 CHAPTER XX. ox THE FATS AM) FATTY ACIDS OF THE HUMAN BODY. Constitution of Fats — Stearic Acid — Margaric Acid — Palmitic Acid — Oleic Acid — Separation of Fatty Acids — A.cids from Cocoa Butter — Compound Fats — Saponification of Fats — Butyric Acid — Fat Cells — Analysis of Fat secreted by an enlarged Sebaceous Gland — Human Fat — Chemical Relations between Carbohydi-ates and Fats — Phosphorised and Nitrogenised Compounds derived from Fats — Adipocere — Formation of Fat in the Body 407 CHAPTER XXI. THE PETTENKOFER REACTION. Pettenkofer's Original Discovery of the Reaction — Other Substances besides Cholic Acid giving the Reaction — Researches of Kingzett and Hake — List of Substances which give the Reaction with SiU- phuric Acid and Sugar — Substances which exhibit the Test with Sulphuric Acid alone — Glucosides — Acetic Acid may replace Sugar in certain Cases — Piperin is (perhaps) a Glucoside — Special luvesti- oratiou of Camphor which gives the Test Avith Sulphuric Acid and Sugar — Theoretical Considerations — Relations between the Bile and the Brain 416 CHAPTER XXII. ON FERMENTATION, PUTREFACTION, AND THE GERM THEORY OF DISEASE ; ALSO ANTISEPTICS ANT) DISINFECTANTS. Fermentation of Sugar bj- Yeast — Fermentation as a Vital Act — Pasteur's Researches on Fermentation — Respiration of Yeast — Action of Individual Ferments — Bacteriu7n lactis — Liebig's Views CONTENTS. XIX PAGE of Fermentatiou — Berzelius' Notions of Catalysis — Liebig's Views explained — Pasteur's Doctrines re-considered — Lister's Researches on Blood — Tyndall's Observations on Germs — Biogenesis — Abiogenesis — Bastian's Researches on Spontaneous Generation — Cohn's Work on Bacillus subtilis and its Spores — Roberts on Oontagium-Vivuni — The Chemical Theory of Disease — Septicasmia — Splenic Fever — Relapsing Fever — Panum and Bui'don-Sanderson on Non-Li\ing Septic Poison — Enteric Fever and Micrococci — Creighton on Can- cerous Tumours — Survey of the Parasitic Theory of Disease — Typhoid and Scarlet Fevers — Artificial Typhoid Fever — Putrefac- tion — Putrefaction of Eggs — Explanation of the Putrefaction of Serum— Germs are not Contagium — Zymases or Soluble Ferments — A Chemical Means of indicating Putrefaction — The Definition of an Antiseptic and of a Disinfectant — ' Sanitas ' — Other Antiseptics and Disinfectants 424 CHAPTER XXIII. THE PHYSIOLOGICAL ACTION OF CHEMICAL SUBSTANCES. Chloroform and Chloral — Chemical Constitution and its Relation to Physiological Action — Stahlschmidt investigates the Action of Methyl-Strychnium Salts — Crum-Brown and Eraser's Researches — Richardson's Researches on Alcohol — M'Kendrick and Dewar's In- vestigations — M'Kendrick and Ramsay's Researches — Investigation of the Action of the different Phosphoric Acids by Gamgee and his Pupils — Emerson-Reynolds on Physiological Action — Critical Remarks 451 CHAPTER XXIY. CHARACTER. The Nature of Character — Connection of Character with the Body- — Man is a Conscious Machine— Imperfect Comprehension of Man's Character — The History of Life is a Dynamical Problem — Man a Cerebrating Creature — ' Genius ' — * The Fool ' — Man's Responsi- bility for his Actions — The Pathology of Intellect — Life and Cha- racter, and their Beginnings ........ 462 XX CONTENTS. CHAPTER XXV. SHOWING now animal chemistry might be advanced. PAGE Hospital Laboratories — Teacbiug of Physiological Chemistry—Investi- gation of Pathological Cases — Publication of Researches — Suggested Matters for Research 468 Index of Subjects . 47; I Ini>ex of Attthorities quoteh . 481 PART I. G E N E E A L B CHAPTER I. IJS^TRODUCTORY. In tlie village of Vorhout, near Leyden, in 1668, was born the man who in after life founded the science of organic chemistry, properly so called. Learned in medi- cine, chemistry, and botany, he constituted a type of men who in later days have stood out from the crowd of workers, not only as peculiarly qualified to undertake their self-set tasks in organic chemistry, but also as the most successful of workers, if the amount of success be judged by the weight and importance of the obtained results. As Professor in the University of Leyden, Hermann Boerhaave made its meclical school famous throughout the world. Guided by sound ideas of the nature of life, and devoted to the experimental phases of science, he attracted by his discoveries a crowd of students who after- wards became the leading men of their day. Beyond the assumption of a ' vital force ' and mys- terious notions regarding ' vital fluids ' which were sup- posed to exist in animals and plants, the alchemists of Boerhaave's time were without a thought as to the nature and composition of the various matters entering into their substance. It is true that the first observation of plant B 2 4 GENERAL. life was made by the wandering pliyt-ician, Van Helmont (born 1577), who nourished a small tree from a twig of willow by means, as he thought, of pure water. But the experiment was not understood, and Van Helmont said that the tree was developed out of the matter of the water by the agency of vital force. Indeed, it does not appear from the writings of that time that the constitu- ents of animal substances were viewed as partaking of an ordinary chemical identity. So absorbed were the metaphysicists and alchemists in problems incapable of solution by human efforts ; in imaginings outside reason ; and so carried away by fanaticism, that to condescend to the study of nature by ordinary observation was a thing of which they had no conception. It must not be supposed that all tlie labours since the days of Hippocrates and Aristotle, or even of Galen, the physician, had gone for nothing. Vesalius, Harvey, Malpighi, Grew, and others had slowly but accurately worked at the various organs of the body, and demon- strated many functions in the act of life. Boerhaave, however, was the first to apply the principles of experimental chemistry to the materials of which these organs were constituted, and to those exist- ing in plants, and by so doing he obtained various ex- tractives, essential oils, camphors, resins, and salts ; not merely this, but he also conducted investigations upon milk, blood, and bile, and sought to determine how they conveyed nourishment to the body. His contemporaries in pure chemical science were also working industriously, and out of the multiform discoveries of new elements and compounds, theories and specific laws were con- structed and established. Such advances gave to other THE LABOURS OP BOERHAAVE AND OTHERS. 5 men the cue whereby they in their turn increased the sum of knowledge of animal chemistry. Boerhaave not only ascertained the composition of some of the principles obtained from plants, but he went further, and extracted similar principles from the soil in which they grew, and then by beautiful experiments he showed that the rain-water dissolved many of these salts and other matters from the soil, and in this way enabled the plants to suck them up and absorb them. Those parts of the plants which he could not find in the soil he concluded came from the air, and, almost simultane- ously. Hales (a celebrated English chemist) gave, by the method of experiment, a striking confirmation of these views. He determined the amount of water absorbed by the roots and that given off' by the leaves of plants, and found it was through the agency of the little stomata or mouths, previously described by Grew, that plants breathe. It is outside the present purpose to describe in any detail the advances made at that time in pure physiolo- gical science, but so intimately related to what has gone before, and so necessary the whole before it was possible for a Liebig, aided by the great animal chemists, Four- croy and Yauquelin, to establish a new epoch in animal chemistry, was the work of Bonnet and Spallanzani upon annuals, and Haller and Hunter's anatomical investiga- tions, that it is most necessary at least that we should bear them in mind. About 1770, Priestley observed that if growing- plants were kept under a bell jar containing the bad air (carbonic anhydride) produced by burning or breathing, the air was thereby revivified and rendered fit for GENERAL. breathing again, and to support combustion. Although ].^hick had even tlien discovered ' fixed air ' or carbonic anhydride, Priestley did not understand the residts he himself liad obtained, and it was not until some time afterwards that the meaning of the process of plant- breathing was appreciated and understood. Tlie discovery of animal electricity by Galvani in 1789 lost nothing in importance by being accidental.^ It is 'mpossible to pay here even the most cursory attention to the toils of Scheele, Lavoisier, and Cavendisli, and the men who continued their Avork after tliem. It is sufficient for the present purpose to bear in mind that all advance in physiological chemistry depends upon an -ever- increasing acquaintance with pure chemical science, and that without those labours to which we have adverted, and the investigations of Nicholson, Davy, Dalton, and Gay-Lussac, Liebig's work would have been impossible. It is to a brief consideration of this work that we liasten. Since the days of Boerhaave nothing of any great importance beyond the facts we have mentioned was accomplished till the year 1828, when the celebrated German chemist, Wohler, constructed urea synthetically. This was a tremendous victory for the chemists, for it had been loudly maintained that the substances elabo- rated in animal tissues were outside the constructive power of the chemist ; it was said tliat although, the 1 Madame Galvani was skinning frogs for making a soup, while an elec- tric machine was in work at hand ; while the flow of electricity was considerable an assistant who was working the machine touched by accident with his knife the nerve of leg of a dead frog, whereupon the leg began to straggle and move ; these facts were communicated to Galvani, and led him to the discovery of animal electricity. (Buckley's History of Xatm-al Science, p. 259.) LTEBIG ESTABLISHES A IsTEW METHOD. 7 chemist could analyse, he could not synthesise ; he could destroy, but he could not create. But the artificial formation of urea showed how foolish are all precon- ceived opinions; indeed, it has been well said,^ 'that fallacy is the child of preconceived opinion. Precon- ceived opinion is the pretended assumption by man of godly attributes which he does not possess. Man has no foreknowledo;e.' Liebig followed Wohler, and gave extreme conviction by further discoveries to those previously effected. His earlier work was largely connected witJi a subject to which Davy had devoted nmch time and thought, namely, to the conditions upon which the growth of plants depend, and the relations of the composition of soils to such growths. It was not in these directions,, however, that Liebig's work achieved the greatest suc- cess. Hitherto there had existed no definite methods ot analysis by which the composition of carbon compounds could be determined with anything like accuracy, but in 1830, Liebig introduced the plan of heating them in contact with metallic oxides, by which means they are resolved into simple products of oxidation which are readily determinable. It is upon this advance in chem- ical manipulation that the great chemist's fame chiefly depends. By the elaboration of a general method suit- able to most compounds containing carbon and hydro- gen, he placed in the hands of investigators an instru- ment of research more potent and more important than any corresponding discovery in the history of chemistry. Other chemists were not slow to take up, improve, and ^ Thudichum. The Oration given at the 91st Anniversary of the Medi- cal Society of London. Medical Mirror, vol. i., Nos. 7 and 8. 8 gexp:ral. amplify these methods of analysis, and the results whicli have been achieved by their use constitute an epoch in science without a parallel. Through the agency we have described, the composition of most known substances has been determined, and chemists have been led to the discovery of hundreds, ay tliousantls of new com- pounds, many of which have been built up synthetically from their elements ; many, even of those substances hitherto supposed to be inseparable from that mysterious and human-effort-paralysing vital force. ' So great was the impulse communicated by this perfection of method, that from darkness it has led to darkness again ; for, in teaching us the composition of bodies, it has brought us to isomerism. When a new method of investiofation shall o impart a new impulse, we shall again emerge into hght.' ^ Chemical investigation can afford to pause so far as its development is connected with the sister science of physiology, which it has left far behind in the race of advancement. In the earlier days of Liebig, physiology scarcely merited its nairte, for up to that time physiolo- gists had concerned themselves only with the study of anatomy and life functions, so far as this was possible without the aid of chemistry. It w\as a science of observation and deductive reasoning, while metaphysical speculations entered largely into its narrow sphere. In his attempt to apply the processes of reasoning flowing out of chemical discoveries to the phenomena of life, Liebig experienced on all sides the resistance of that parent to fallacy, preconceived opinion, and, abandoning the opinions of his contemporaries, he devoted his teach- ^ Physiology, and its Chemistry at Home and Abroad, by C. T. Kingzett and H. W. Ilake, ' Quarterly Journal of Science,' January 1877. THE TEACHINGS OF LIEBIG AND OF MILL. 9 ings to a younger generation possessed of a more plastic mind. He saw how futile it was to struggle with a race of men of whom he was in apparent and such striking advance, and as for their metaphysical vieAvs, he argued that such must render men powerless in time to perceive the relations of cause and effect. He devoted himself with much earnestness of purpose to expose the unscien- tific methods of reasoning and research so prevalent at that time among physiologists, and ever advocated the principles of that inductive logic so ably interpreted by a man Liebig professedly admired, John Stuart Mill. Thus he gathered around him, in spite of all opposition — for truth was ever stronger than prejudice — a group of men who, by adopting and disseminating his teachings, gave rise by their labours to a new epoch in animal chemistry. It would be of the deepest interest to follow up the work thus originated ; to watch the ever-growing wave of knowledge in its resistless advance; to study those lines of thought and investigation whose pursuit has led by rapid although imperfect advances to the idea of the beginnings of life and the germ theory of disease. It is true that men have here and there lost sight of those principles underlying all sound research, and have oftener plunged wildly into the mazes of uncerebrated research, the results of which, by their interconfliction, have hindered rather than helped scientific advance. But this is a phase of modern times that we have no in- tention of dwelhng upon here ; unfortunately, there will be only too much opportunity and necessity for its revelation in future chapters. Here let us consider Liebig's philosophy somewhat more in detail. He as- sumed the existence of a vital force, or whatever we 10 GENERAL. choose to call it — say, an agency — powerful to develope from the seed the plant, and from an egg the bird ; but at the same time he acknowledged above all men, and insisted upon the truth of his admittance, that the actual ])rocesses of life, with all their complications of function, were based upon the same laws which operate between matter and force in the chemists' laboratory. The history of all science shows that it developes, first, by the accumulation of isolated facts ; secondly, by the discovery of determining influences, and of certain relations between those facts ; thirdly, by the deduction of general laws from larger series of observations than those upon which special laws depend. Finally, it be- comes possible from given conditions to predict the next states of certain forms of matter. To these rules physiological science makes no exception. The pheno- mena of life stand like those of dead or inorganic matter in certain co-relations which are determined by specific causes ; and it is only in the light of a knowledge of these causes and their nature, that the processes of life can be ascertained. Such a search constitutes the most important problem in physiology, for by it is to be dis- covered the mutual dependence of the vital phenomena. It is true that anatomy here is of great avail, but, un- aided by chemistry, its discoveries have comparatively little meaning ; not only is the anatomical method in- sufficient of itself, but it is subordinate to the chemical method. !Such were the opinions of Liebig. There are those who hold the opinion that in life there is something which renders negative all our con- clusions drawn from laboratory experiments, and nullifies all our hypotheses of functions, but they are men who THE NATURE OF VITAL FOECE. 11 fail to grasp thoroughly the conditions upon Avhicli life | depends. The vital force, compound by nature as it is, partakes in its component parts of the same character as the chemical force, inasmuch as it only acts when the particles are more or less at infinitively short distances from each other. Life itself is the expression of the metamorphoses of the animal tissues ; in other words, man lives by virtue of certain changes of matter in- cessantly going on in his body, and what is chemistry but the study of the laws of changes of matter ? Surely, it has no further meaning. The dogmatism of churches and ages, the unreason- ing and prejudice always associated with ignorance and untrained and unscientific minds, have done their worst and they have done their best, but what explanation of life, health, and disease have they given ? 'None ! They have told us that nervous force emanated from a nervous system, and that cooling substances are astringents ; they ? have invoked superstitions and conjured up groundless faith in an agency whose function they could not define, , and of which they thought it was blasphemous and ./ wicked to enquire. This dogmatism, this circumscrip- tion of language, received from Kant in his earlier writings long ago, what in more recent days it has received and merited at the hands of John Stuart Mill. And, although churches still boast their superstitions under a cloak of rehgious faith, and although men's minds are still tainted with that bias against improve- ment so common to tlie savage, the further pursuit of science will overpower and destroy it all in due time. We may not live to see it, but it is as inevitable as the daily setting of the sun. 12 GENERAL. But to return to our more immediate theme. Tlie object of physiological chemistry, then, becomes the re- duction to general laws of those phenomena which, in their multifarious co-relations, constitute the functions of life. To prosecute this study witli hope of success, it is essential that we should first become acquainted with the composition and constitution of those substances which are elaborated in the various tissues, organs, and fluids of the living body, and of which these are themselves consti- tuted. It is only by means of such knowledge that we can be enabled to trace out the intricate concatenations of the various parts of the animal body, and of those metamorphoses which are constantly in process in the living laboratory. Such studies are as necessary to phy- siology as it is to ascertain the composition of hydro- chloric acid and chalk, before we can explain any action they may have one upon the other. From what has gone before, it will be apparent that the method to be pursued in the study of pathology is identically of the same order as that requisite for use in physiology, and the results of these parallel investi- gations appear as the expressions of health and disease. Mr. John Simon has well expressed ^ this truth by describing pathological results as the 'morbid declen- sions' from the 'normal chemical standards' of Jjhysi- ology. While the method to be pursued in such studies is plainly visible, and when the results to be attained are so all-important to the prosperity and health of man, it is surely matter for deep regret that there are but very few ' Reports of the Medical Officer of the Privy Council, SjC. New Series, Ko. 3, p. 8. THE PURSUIT OF ANIMAL CHEMISTRY. 13 men availing themselves of it. Not only is this true of England ; it is true in a different measure of Germany, France, and other nations. The reason for this is not far removed. It is true that in the science of physiological chemistry there are pending matters for research which might fairly be undertaken by men of ordinary attain- ments at very httle expense ; but there are many ques- tions (and these are the most important of all) to be solved, which are much further removed from the abilities of the untrained mind, and which demand for their eluci- dation means and time at the command of but few private individuals. This is notorious and acknowledged. I contend, however, that even were there men who have the time and the means whereby to grapple with these problems in science, there is not, at least in our country, any system of training })y which such men find it easy to qualify themselves for such studies and researches. The result is, that the work is to a large extent neglected, or, when undertaken, from the reasons stated, the results at- tained are often lamentably worthless or deficient. The truth of this statement is not to be gainsaid ; it is a matter of everyday experience, and to those who are conversant with recent scientific literature, these remarks will furnish no matter for surprise. It were easy to substantiate these statements, but it is unnecessary, it having been already done.^ On the successful pursuit of the study of animal chemistry, all medicine rests. Diseased livers, brains, hearts, and lungs ; organic and chronic diseases ; cholera, typhus, and typhoid fevers ; all these and hosts of other ' See Essay in Qum-terly Journal of Science, bj C. T. Kingzett and II. W. Hake. January 1877. 14 GENERAL. diseases and disorders, no nuittcr wliat their causes or tlieir origin, liave something in common. All diseased organs and all morbid processes speak of chemical changes and processes different from those actuating and controlling the organs, tissues, and fluids in health, and of necessity, therefore, curative and preventive medicine must in the main have its basis in a knowledge of histo-chemistry. At present, medicine is rather an accu- mulation of experiences than a natural science, whereas it ought to occupy the leading place in science, in fact shine out as that ultimate focus in science upon which and towards which all other science sheds its rays of light, and to which human efforts should be above all things directed. Many are the medical men who saj^ and say with considerable show of reason, all this is very true, but if we stay in life to study animal chemistry and the chemical changes underlying pathological processes, our patients will die in the meantime. It is true we are terribly overmatched by disease, but still we can do something to stay its progress, and to that something we must devote ourselves. Who then is to prosecute the science, if the medical men will not or cannot? The chemists ? Unfortunately, physiological chemistry is not taught as an ordinary part of the science, and chemists who ordinarily devote themselves to research, fmd such labours too tedious or too unprofitable in results, and so the work is left undone for the most part, and in the meantime disease ravages mankind, and demonstrates in a terrible manner how futile are our strongest efforts to stay its progress. Still something might be done if the system of teaching at medical schools were improved. THE POSITION OP ANIMAL CIIEMISTEY AT HOME. 15 Animal chemistry finds no advocates at our Universities ' and public schools, and is not embraced in their curri- culum ; it is professedly taught, however, at our medical schools ; but if one takes the trouble to enquire into this teaching, one is rudely shaken in their beliefs. What is really taught is not animal chemistry, but a certain num- ber of facts. The students are made acquainted in an empirical manner witli the ordinary methods of separation employed in the qualitative analysis of substances, which, for the most part, do not occur, and have little to do with the animal body ; they are taught certain tests for poisons of various kinds, and are put through, it may be, a few exercises in quantitative analysis of inorganic sub- stances. Their learning is crowned by cramming a fur- ther number of facts regarding the blood, the urine, and bile, and imbued with this knowledge they enter on their medical career. This is not the way to teach animal ■ chemistry, and the teachers are to a large extent incom- petent to fulfil this task. To appreciate and to pursue this study, a previous knowledge of ordinary chemistry, and a wide one too, is requisite ; moreover, a more than superficial acquaintance with physics is required, and, for most purposes, an understanding of human physiology. Then, again, facts do not, constitute a science ; science is '-^'^"^'i U^ constituted of principles ; and from our teaching, and our text books, and our teachers, from none of these do medical students of to-day learn these principles. Of the teaching and the teachers we have already spoken ; as for most of the text books in use, not only in this country, but abroad also, they are the merest compilation of facts — facts picked up here and there and arranged together in chapters ' specially designed for the medical 16 GENERAL. student.' Alas ! for the medical student ; he finds no philosophy in them, but only a certain number of state- ments with which he must make himself familiar without understanding them ; a certain array of facts which he must learn as he learnt dates of historical events when a boy at school ; facts without a binding link ; statements possessing no exhibition of relation ; the whole devoid of connecting principles and a scientific philosophy. In the face of what has been shown, is a man having such knowledge as- he may acquire at our medical schools well fitted to understand the processes of health and disease? has he any power to add to our knowledge of these things ? Moreover, the books of the day have another grave fault ; they are not only imperfect so far as they go, but they do not go far enough. Recent and the most im- portant scientific researches find too often no mention, or when they do, the accounts are, not rarely, worse than useless; they mislead from their inaccuracy; they injure men by the prejudice they exhibit. It is quite true that one half of the world does not know how the other half lives. There are people who talk of the republic of science as others once talked of the repubhc of letters. Alas ! for the republic of science. In art, in hterature, in law, in medicine, in fact, probably nowhere at the present time is there so much bickering, jealousy, and conceit as in the infant republic of science. Not only is this true of private life ; there slander, machi- nations, and prejudice are exerted to the full. This is bad enough, but it is too bad to carry this sort of thing into public life and scientific literature, and yet it is done, and on a glaring scale too. The consequence is that our THE EEPUBLIC OF SCIEIsTE. 17 literature loses in value ; the teaching of the day is frus- trated by external politics ; the whole system of science receives a serious check. Boast is made of the rapid progress of science. Bah ! it is untrue. Science never did, does not, and never can make rapid strides. Eelatively, progress may be rapid, but it is only relative to times when progress was much slower. But if men would only throw aside, at least in certain w^alks of hfe, jealousy, prejudice, and partiality, and unite in a true and honourable republic of science, how much better would it be for science. There was never a finer example set by man than that taught to the disciples of alchemy, ' Ora ! Lege, Lege, Lege, Eelege, Labora et Invenies.' ^ ^ See Mr. Rodwell's Birth of Chemistry. 18 GEXliEAL. CHArTEK IT. LIFE : FROM A CHEMICAL POINT OF VIEW. For the purposes of the present work it is not requisite to enter at all deeply into the anatomy of the human body. In order to show the processes according to which man ' lives, moves, and has his being,' it is but necessary to regard him as a conscious machine or an automatic instrument. Nor is it necessary to have regard to man's place in nature beyond its enunciation. Pos- sessed of conscience, will, and power, he finds himself as the creature of a generation composed of beings like himself, exhibiting certain relations among each other. Of the individualities or character we shall have a little more to say later on ; it will sufiBce here to recognise the individuality of man. This individuality, controlling the w^hole life-actions, is unfortunately almost universally ignored, or where it is not ignored, it is not rarely mis- interpreted. The doctrines of evolution and survival of the fittest, and all those thousand minor laws which in view of the teachings of men hke Darwin, Spencer, Wallace, and others, we hold to be true of lower forms of animal life, are true also of man. He is the resultant of a thousand conflicting predestinations and emotions ; the focus of predispositions and circumstances that have been in action for ages. Wliere then lies the difference of individualities ? Partly in the brain power ; partly in MAX, AS A CONSCIOUS MACHINE. 19 the individual organs of the body ; partly in the general relations these bear to one another, and the whole of them to the brain power. For, in a general sense, all men are constituted alike ; the philosopher Aristotle, Homer the poet. Mill the logician, JSTapoleon, of iron will ; all these, and all men, are in their physiological form ahke. The characters and individual powers of these men are to be traced not so much to any individual difference of form of the various organs of the body, but rather to quahties possessed by some or all of those organs ; qualities which have a quantitative expression, but whose meaning is hidden deeply in the tissue of which the organs themselves are composed To return, however, to our consideration of man as a conscious machine having complicated functions, that is to say, a machine powerful to do muscular and mental work by viitue of a force generated in situ, and guided by will. It is a fact of the deepest meaning that the food which we eat takes part in that with which we think, and the body having once attained a full develop- ment of form and size, food henceforth represents one side of the equation of life ; on the other side is repre- sented the history of our life. It is not intended to study those processes of develop- ment and growth antecedent to maturity ; it is sufficient to bear in mind that there is a beginning, an embryo phase, and intermediate stages of life. But from the beginning there is an inherent power in the life substance, caU it protoplasm, bioplasm, or what we may, which determines the evolution out of its own elements, of tissues and organs, and which constantly regenerates itself, so to speak, from the food presented to it. c 2 20 GENERAL. Hence we may fairly say tliat tlie luiman body is a mere apparatus by the agency of which man lives in another sense, viz. the mental or intellectual sense. The -fc:,^ study of the construction, of that apparatus constitutes the science of physiology ; the life which is maintained in and by the human body is the result of chemical changes inces- santly occurring in the matter of which the tissues and organs and fluids of the body are constituted. The same life depends for its continuation upon the food which is taken into the body, and from which there are elaborated new fluids, and new tissue to replace that previously lost by the act of hfe. When the processes we have alluded to, follow an inherent determinated direction, they may be conveniently summed up under the title of physiological chemistry ; but when declensions arise the processes are morbid, and the result is disease : this study constitutes the science of pathological chemistry. Together, these two subjects are included in the expression ' animal chemistry.' Let it not be thought, however, that there is in this description any desire to hide away that which we cannot explain. In life, anatomy has its share and chemistry and physics have also their parts. All these subjects, however, cannot be considered together, and tliis state- ment is here made in order to avoid the stigma which Henle attached by his criticism to Liebig's work on ' Animal Chemistry.' Henle wrote : ' With consummate skill he (Liebig) draws a few crystalline threads out of the tissue of life, and holds them up to admiration as the share of chemism ; he then throws us tlie lump which he cannot unravel as the share of vitalism.' Kow according to the above showing, a man requires EfiSUME OF PEOCESSES OCCUREIXG IN THE BODY. 21 to take daily a given amount of food properly prepared by cooking and otherwise. This is comminuted in the mouth and is there mixed with saliva ; as it arrives in the stomach it is farther mixed with various fluids and secre- tions, including gastric juice, bile, pancreatic juice? and so on, and here digestion partly occurs ; it is completed in the smaller intestine, and the undigested and valueless part of the food is excreted as faeces. The chyme and chyle thus formed are conveyed by proper vessels to the blood system, and by means of the heart's action are dis- tributed throughout the body. As the blood circulates through the system, the various organs assimilate from it the nutriment they require to reconstruct themselves and keep in working order ; at the same time they yield to the blood the soluble effete products of life ; products result- ing from decomposition and change, upon the carrying out of which their very functions depend. In this way the blood passes on to the kidneys, through which it filters as it were, and allows the worthless part of it — that con- sisting of the excrement! tious products — to be removed as urine. Simultaneously with these processes occurs that of respiration, an act which depends upon the inspiration of air and its passage through the lung tissue into the blood. This oxidising effect is carried out by the blood in all parts of the body, and in return that fluid takes up carbonic acid — a product of oxidation — which is after- wards duly eliminated through the lung tissue also, viz. at the moment when the blood arrives there for a fresh supply of oxygen. It would also appear that man undergoes a cutaneous respiration, although in a smaller degree, much water and certain other matters being eliminated through the skin. Each and all of these 22 GENERAL. processes will be fully considered hereafter, and this re- sume is given merely to demonstrate, at the outset, how great a share chemistry takes in life. It concerns itself with the nature and composition of the food taken ; with sahvary, stomachic, and intestinal digestion ; not merely so far as these processes themselves are concerned, but also with the composition of the various ammal juices taking part in them, as well as with the very composition of the organs which secrete the said juices. Then again, chyme, chyle, lymph, blood, have each their chemistry and inter- relations, and, what is more important, the act of respira- tion is essentially a chemical one. This then has to be studied, as also the methods by which the organs and tissues of the body oxidise and repair themselves. That these organs, such as the brain and lungs, have a chemistry, is a matter which has only of late years received the atten- tion the subject merits, for, as previously stated, there were in past times not wanted men who denied, or at least did not recognise, the fact of their chemical compo- sition. Finally, there is the chemistry of bone and muscle, and of the various excrementitious matters, such as sweat, urine, faeces, and breath. Regarding the various subjects just enumerated, our chemical knowledge is both small and great ; that is to say, it is great in itself, but does not nearly represent the whole possible knowledge. The chemistry of digestion particularly is but little understood, whereas there can be no doubt that an increased knowledge of the com- position and properties of those specific ferments which take part in it, would lead to an immense gain, not only for human physiology, but also in our appreciation of the meaning of fermentation as a general phenomenon. THE SHARE OF CHEMISM IN LIFE. 23 With the subject of ferments is intimately connected one which of late years has attracted a predominating amount of attention, namely, the germ theory of disease and in- fective processes ; and, once arrived at this stage, we verge upon the beginnings of life. It cannot be doubted that for the future progress of our knowledge of these questions we must look more to chemical science than has been done in the past. It is too true that our slight know- ledge of the composition and inter-relation of bodies occurring in the human system, and of the processes by which they are built up from food and transformed into ultimate products after fulfilling the vital functions, only shows how much yet remains to be learnt. It is soon perceived that we stand but on the threshold of know- ledge, and many must be the thinkers and workers, and generations upon generations will pass away, before the processes of life shall stand forth entirely revealed ; before it shall be known how, from a few simple matters tolerably well known themselves and administered as food, is built up man with his marvellous and beautiful structure, with his power of thought, feeling, and action. That such a time will come scientific men have no doubt ; we shall know more to-morrow of the sun that shines to-day ! There is darkness around the vital phenomena, but that darkness exists only because science has not yet attacked nature and illuminated it sufficiently by its dis- coveries, waiting to be effected in these directions. There will always exist men who will doubt the possibihties of science ; who will call in question matters which have been established as truth for all time, just as men, even to Bacon, rejected the doctrines of Galileo, 24 GENERAL. and as Leibnitz spurned the philosophy of Newton on gravitation. But, in spite of all, the sun of science will dispel the morning cloud of ignorance and prejudice, and will unfold to us the laws of nature unbiassed by the poetry of man's mind and free from the superstitions of churches. WHAT CHEMISTEY CA^' TEACH US OF LIFE. 25 CHAPTEE ni. CHEMISTEY AS APPLIED TO PHYSIOLOGY AND PATHOLOGY. Although this work pre-supposes a certain knowledge of chemistry on the part of its readers or students, it may yet be desirable to make a few observations regarding the classification of carbon compounds, inasmuch as the greater part of the human body is made up of such sub- stances. In doing this, it is not proposed to consider the reasoning upon which the various systems of classifica- tion are based, nor to comment upon the relative values of them, but rather to supply an explanation, brief though it be, of terms and names which will be found in use throughout this work. Moreover, while a system of classification is all-important in certain branches of pure science, it serves a far minor although important service in a science like that of which we are treating, and for this reason ; that the function of physiological chemistry may be said to consist in the elucidation of those pro- cesses by which life with all its many side-issues and declensions is maintained. In this study, chemistry is competent to teach us how from certain substances given as food, the constituents of the body are produced ; and again, how these products sufier subsequent change, and give rise to other and excretory substances. In other words, the physiological chemist, having regard to his ultimate objects, seeks to determine the relations existing 26 GENERAL. between different substances supplied to, found in, and excreted by the body. It is upon a knowledge of such relations that he is enabled to understand the processes of life ; that, in fact, he is able to hope for the attainment of his object. In such a search it is not requisite, at least in the present state of the science, to consider the chemical constitution of bodies in greater degree than that which is requisite to show how this substance is produced from that substance, or this other compound may give rise to that other compound. In short, chemistry as applied to physiology is a means of working out dynamical equa- tions in which certain masses are dealt with on the one side, and on the other, lesser sums, the total of which is equal to the original mass. To instance our meaning, let us deal with a body like fat, which is known to yield glycerine and fatty acids when decomposed in a certain manner. The chemist has a particular interest in deter- mining, not merely the general properties of these sub- stances, but also in seeking to ascertain their actual constitution, or the manner in which the atoms entering into their composition are arranged. By the application of certain tests he can tell the general nature of sub- stances, and can place them by the side of others of similar characters, and believed by him to have a corre- sponding or comparable constitution. True that such a method has its meaning, even in physiological chemistry, but what is more directly important to the physiological chemist is the quantitative determinations of the total products obtained in the particular decomposition of fat referred to, and such other instances. The chemist may obtain one product upon which he may devote imhmited study to ascertain its properties, THE DYXAMICS OF ANIMAL CHEMISTRY. 27 general nature, behaviour to reagents, and constitution, whereas the physiological chemist should seek rather to devote his attention to all the products, until not only the individuality of each is established, but until their sum is equal to the mass of matter from which they are originally produced. Again, we shall see in another chapter that, chemi- cally considered, leucine is an amidated fatty acid, and chemists have made themselves well acquainted with it, its character and constitution ; they also know it to be obtainable from albuminous substances, and further know it, when thus prepared, to be identical with the leucine prepared by artificial synthesis. But this is not enough for the physiological chemist, who seeks to ascertain exactly its amount and the nature and quan- tities of all other substances by which it is accompanied when made from albumin. Further, it is important for him to know whether it can arise from other sources in the body, because, if not, he is at once able to indicate its origin under any particular set of circumstances, and, indeed, is in a position to make a sort of generalisation. Now, of late years, there has been introduced into chemical teaching the so-called ' structure ' hypothesis of carbon-compounds, under which these latter are repre- sented as structures comprised of constituent atoms ar- ranged graphically. This graphical arrangement is arrived at from a knowledge of the way in which substances decompose when subjected to particular processes. That is to say, if they yield by some process a particular sub- stance, this is considered as sufficient evidence that they contained in their structure a particular group of atoms ; and so far so good. But many chemists go further than 28 GENERAL. this, and say not only that such and such a group is present, but also that it is present in a certain position. It is this last-named assumption that is so extremely un- profitable and unmeaning, particularly for physiological chemistry. Being purely hypothetical, it has no place in true science or healthy logic. Let us try to indicate how far lomcal reasoning enables us to indicate the constitu- tion of substances. Glycocholic acid, when decomposed with dilute acids or alkalies, yields cholic acid and glycocine, and as the process employed is a mild one, and as these are the only products, it is inferred that in the original molecule of glycocholic acid, these sub- stances, or residues of them, were co-existent. But even this is mere inference, because if glycocholic acid be submitted to other processes it yields other products, and applying the same reasoning, we make the rediictio ad absurdum that this substance contains, as primary or proximate nuclei, such a number that the sum total of their elements is greater than the amount of substance operated upon. To say that because a certain substance yields certain other substances by a particular mode of decomposition, therefore residues of these latter must have been present in ihe parent molecule, is an assumption having ad mittedly more or less plausibihty and even usefulness, but it is an argument which must not be pushed too far, or at least must be limited by very clear definitions. This is so, because it appears equally good reason to say that, since by acting upon a particular substance with another substance a third one is produced, and is un- attended with other substances, therefore this new sub- stance contains groups or radicles previously contained THE STRUCTUEE-HTPOTHESIS IN CHEMISTRY. 29 in tlie two separate ones ; but sucli reasoning as this soon leads us into a fog, since very often the same sub- stance may be prepared in half-a-dozen different ways, and from substances of such different natures that ob- viously these could not contain a common group. The fact of a chemical reaction cannot be exceeded, and a chemical equation may or may not express the whole truth. When carefully thought out, it becomes clear that chemical constitution is a phrase of little mean- ing ; it is a something conceived to have a relation of some sort with the substances from which and the manner in which a body is produced, and again, the substances into which and the process by which it may be resolved. In short, and curiously enough, the chemists who most bravely defend the ' structure ' theory of carbon compounds, have latterly assumed a position which indicates its own indefensibihty. For example, benzene, when submitted to various processes, is capable of yielding hundreds of different substances. ' Structure ' chemists may write benzene as a graphical arrange- ment of carbon and hydrogen atoms, in which each carbon atom is directly united with a hydrogen atom, and continuously with all the other carbon atoms. But putting aside the illustration for what it is worth — the particular figure varying with the author — their structure amounts to the recognition of the fact that in benzene there are six carbons united with six hydrogens (CeHg) and amounts to nothing else. ' Structure ' chemists are not without a kind of reasoning in defence of their propositions, but it is a sort of reasoning not compre- hended in the science of logic. In fact, the structure theory of benzene amounts to nothing more or less than 30 GENERAL. the statement, made in a particular way, that benzene consists of two elements, and that if a certain quantity be taken and submitted to the action of a certain quan- tity of other substances, it may yield a number of sub- stances, but supposing that from these the benzene could be got back again, then the amount would be equal to the original quantity •taken. In other words, it is true that, given a mass it is possible to break it up into parts the sum of which equals the original mass. Vary the means employed to break it up, and with them the parts or products differ also. For the purposes of physiological chemistry, it is sufficient to understand the meaning of a chemical re- action, and it is desirable that a chemical equation illustrating such reaction should be as far as possible a mathematical equation in the sense that the other side should specify not one particular product, but embrace all and indicate their relative amounts. These amounts should be equal to the acting masses represented on the first side of the equation. The Chemical Principles and Educts of tlte Body. — It will be seen from the contents of the following chap- ters, that a large number of the substances found in the body are of huge molecular proportions, and do not admit, so far, of any reasonable classification. Thus it will be shown that there are reasons for regarding haamatocrystalUne, or the colouring matter of the blood, as a distinct chemical individual of probably greater com- plex constitution, than fibrin. So complex indeed must be its constitution that even one of its decomposition products hasmatin — is of undetermined structure. Again, the immense variety of albuminoids cannot be formulated CLASSIFICATION OF ANIMAL SUBSTANCES. 31 Upon a general type, while many of their decomposition products require much more study before they admit of classification. Chemical researches have already led to general formulse for many of the brain principles, in- cluding the phosphorised substances aUied to lecithine, C43H84NPO9, but of the constitution of the cerebrines and other substances, next to nothing is known with any degree of certainty. While, therefore, it is impossible to comprehend many principles and educts in any system of classification known to chemical science, the same cannot be well said of the better known simpler substances which are not peculiarly of animal origin, and they embrace represen- tatives of almost every type of chemical substance. The majority, however, of these classifiable bodies consist of alcohols, acids, amidated acids, and amines. Hydrocarbons, or compounds consisting exclusively of carbon and hydrogen, do not occur in the body, nor are they contained in the food ordinarily partaken of by man. One may well conceive that under the universal condition of oxidation which obtains in the living body, it would be, perhaps, impossible for any hydrocarbon to per- manently exist, even if elaborated therein. The alcohols, chemically considered, are substances containing replaceable hydroxyl (HO) ; or they may be regarded as substitution derivatives of the hydrocarbons ; thus ordinary ethylic alcohol may be written C2H5(HO), which signifies that it is the hydrate of ethyl. These compounds are the analogues of the metalhc hydrates, and extend to and embrace many carbohydrates be- longing to the groups of starches and sugars. Many alcohols, therefore, enter into the composition 32 GENERAL. of our food, and not onl)^ so, but they are also probably- elaborated witliin the body itself, in some cases by a pro- cess of hydration operating upon suitable originating substances. In this way all giucosides yield sugar, and many starches also yield sugar. Mercaptans, or thioalcohols, of which ethylic sulphy- drate (C2H5IIS) is an example, do not occur, so far as is known, within the body, nor is it possible to say whether the sulphur contained in some albuminous substances exists in combination in some such form. If any of the starches constitute ethers (as the anhy- drides of the alcohols are termed), then these form not only part of the food, but are also found in the body, as for instance, glycogen (CeHjoOa) in the liver. The ethers are converted into alcohols by heating witli water or alkalies, thus ethylic ether becomes ordinary alcohol as follows : (C2H5)20 + H20=2C2H5(HO). Glycogen under the same treatment takes up water and becomes sugar. But the true constitution of the bodies known as starches is far from being accurately determined, and in the chapter on carbohydrates, it will be sliown that some forms of starch are regarded as aldehydes, or compounds intermediate between the alcohols and the acids. The aldehydes are regarded as hydrocarbon derivatives in which hydrogen has been substituted by a monatomic radical group (C'^0"H)'. Thus ordinary alcohol gives rise to the formation of ethylic aldehyde when subjected to partial oxidation, CH3CH20H + 0=CH3(COH) + H20. By further oxidation acids are produced, as for ex- ample :—CH3(COH)+0=CH3CO.OH— this equation re- presents the oxidation of aldehyde into acetic acid. It is thus seen that in an ultimate sense, acids may be OKGANIC ACIDS OF ANIMAL ORIGIN. 33 regarded as oxidation products of hydrocarbons, in which hydrogen is replaced by a monad carboxyl group (CO. OH), and as there are different series of hydro- carbons, so there are various series of acids. They all furnish metalhc salts, haloid salts, ethereal salts, amides, and whole series of other compounds of more peculiar interest to the chemist. Of the acetic series, a large number of members occur in the body, and are obtained by processes of decomposition from various substances of animal origin. The acetic series is derived from the hydrocarbons of the general formula CJl2n+2^ f^nd is represented by the gene- ral formula CnH2ii+iC0(0H). It consists of homologous members, differing by CHg, as shown by the following examples. Methylic or Formic acid Ethylic or Acetic acid . Propylic or Propionic acid Tetrylic or Butyric acid Pentylic or Valeric acid Hexylic or Oaproic acid HOO(OH). CH3.00(OH). O^Hj.OOCOH). C3H-00(0H). O.HgOOCOH). 0,H,,00(OH). All these may be obtained from animal sources, and notably by the oxidation of albuminous and other sub- stances. The following are also of interest to the animal chemist, and belong to the same series. Palmitic acid . . .... CijHjiOOCOH). Margaricacid OieHjgOOCOH). Stearic acid Cj^Ha^OOCOH). The Acrylic, or CjiH2n_iC0(0H) series of acids, de- rived from the CnHgn hydrocarbons, is represented by oleic acid, with which we shall make ourselves acquainted in other chapters. D 34 GENERAL. The Benzoic, or CnH2„_7CO(OH) series of acids de- rived from tlie CnHjn.g series of liydrocarbons, is repre- sented by benzoic acid, CcH5C0(0H), and other sub- stances. Again, the Acetic series gives rise to a secondary series, known as the Lactic, and of the general formula CnHo„(OH).CO(OH) ; while from the Benzoic series, another secondary, Salicylic or CuHjn— 8(0H).C0(0H) series may be derived. The juice of flesh contains two isomeric lactic acids, one of which appears to be identical with ethylenic lactic acid, Avhile the other, sarcolactic or paralactic acid, as it is variously called, is distinguished by its power to direct polarised light to the riglit. Its products of oxidation are identical with those derived from ethylidenic lactic acid. Among the many derivatives of the acids, none are of so much interest to physiological chemistry as tlie amides. Artificially, these substances present no difficulty in formation ; thus they may be readily obtained by the action of ammonia on the acid chlorides, as for example : CH3COCI + 2NH3 = CH3.CO.NH2 + NH.Cl, or by distillation of the ammonium salts of the acids ; thus, CH3CO.ONII4 = c1i3.co.NH2 + on^. Of course each series of acids gives rise to its own amides, which may be viewed as compounds formed from the acids by replacement of the (OH) group in the carb- oxylic group by the monad residual radicle (NHg), (ami- dogen derived from ammonia, KEI3). Tlie monobasic acids yield only normal amides, while AMIDES' AM) AMINES. 35 dibasic acids give both normal and acid amides, or amic acids as they are termed. In the chapter on albuminous substances it is shown, that in the decomposition of these bodies by a process of hydration, a large number of amides and amic acids are obtained. There are representatives of these substances also in the urine, notable among them being hippuric acid (benz-amido acetic acid). The only other class of bodies we need notice here is the amines, which are viewed as being derived from ammonia by the substitution of hydrocarbon groups for hydrogen. The amines, or compound ammonias, as they are also termed, may be grouped into three classes, namely monamines, diamines, and triamines. Thus we have among others the following mon- amines : — Primary. Secondary. Tertiary. fOA nJo.h, H nJo,h, nJh H 0.H, Ethylamine. Diethylamine. Triethylamine. have also :- - Monamiae. Diamine. Triamine. NJH H nJ,h, |0,H3 N3JH3 H3 (H^ Amidohenzene. IHamidobenzene. Triamidobenzene. These amines are well represented in physiological chemistry by urea or carbamide CO(NH2)2, and the large number of derivatives to which it gives rise, as also by trimethylamine obtained from various animal substances by distillation. As another representative, although of a more complex kind, we may example D 2 36 GENERAL. neiu'in, or the ammonium base obtained in the decom- position of the phosphorised principles of brain matter. All these organic ammonias strongly resemble ammonia in their properties, combining directly with acids to form salts, by treatment of which with oxide of silver the corresponding hydrates are obtained. Tims — C2H5.XII2 + HCl = C2H5.XH3CI. and 2CjH,.NH3Cl + Ag,0 + H,0 = 2O2Hj.Nrr3.OH + 2Ag01. The hydrates obtained in this way are caustic substances, exhibiting many of the properties of their analogues, the caustic alkahes. Chemical Changes Occurring in the Body. — The chemical decompositions for ever occurring in the living body are all included in two processes, viz., those of hydration and oxidation, that is to say, they are decom- positions depending upon the assimilation by substances of the elements of water, or upon the action of oxygen. These processes occur of course separately, but they may be, and often are, associated in succession. They are of sufficient importance to merit some special con- sideration in this place, and glancing lightly over the ground which is covered more particularly in the various chapters, a number of instances of hydration and oxida- tion may be en passant referred to. For instance, the starch of food is, in the mouth and stomach, transformed into sugar by the assumption of water, an assumption directly caused by the unexplained ferment-like or contact-like power of ptyaline. Again, the amyloid- substance of the hver is supposed to undergo a similar change, or, yet again, fats in course of digestion are like- THE PROCESS OF HTDEATIOX. 37 wise split up by hydration into fatty acids and glycerine. In pathology, the hydration process is apparently of yet greater importance, thus, for example, in softening of the brain, one of its principles suffers disintegration in this way. The following equations show these changes, which are seen to depend upon the direct assimilation of water by the bodies thus changed. C3Hjoi3H3;o,' + 3H,0 = 0,H,(H0)3 + 30,3H3,0, (^18^3502 fOisHaaOj C3HJ0j,H3,O, + 3H,0 = G,-H,VO, + C.H^.NO + (H0(0P0)05Hi3N0 C18H34O2 + OiflHjoOg. This assumption of water takes place, in numerous instances, at the ordinary temperatures, but for other cases, a more or less elevated temperature is required. This latter condition is, of course, provided in the animal body also. Changes by hydi'ation may result from mere contact with water of the bodies to be changed ; in many other instances they occur by the intermediation of a third body, such as dilute acids or other substances, partaking of the nature of a ferment or zymase. The specific manner of this intermediation is undetermined. It is by a process of hydration that albuminoids in the stomach are changed into peptones, and again, it is by a similar process, perpetuated further, that these are decom- posed into such proximate nuclei as tyrosin, leucine, &c. Oxidation, as a process happening outside the body, or in the laboratory, is very well understood. There are 38 -GENERAL. degrees of oxidation as there are degrees of hydration, and these depend upon the nature of the oxidising agent and the conditions under whicli the process is efTected. Thus the products of the oxidation of turpentine, for example, differ according as the oxidant be air, or nitric acid, and so fortli. It is so-called ' limited ' oxidation that is of peculiar import in studying the chemistry of animal and vegetable processes ; in other words, it is oxidation by air Avhich chiefly concerns us here. In some cases hydrogen is removed, having com- bined with the oxygen of the air to form water ; this happens with alcohol as follows : — C.HsO + 02 = II^O + CjH^Oo ; or the reaction may go further in the body, perhaps, and give rise to water and carbonic anhydride only ; thus — 0,11,0 + 70 = 311,0 + 2002. Or, again, oxygen may not only remove hydrogen from substances in this way, but may also attach itself simul- taneously. It is doubtful whether such a state of things ever happens in the animal system, but it is quite con- ceivable, inasmuch as one may realise it in the labora- tory. Further, oxygen may resolve large molecules into simpler ones, with the elimination of water and the pro- duction of oxidised compounds. Thus — CjHoO + 3O2 = H2O + CjHeOa + 2O2H4O2. Here, triethylcarbinol is resolved into propionic and THE PKOCESS OP 'LIMITED' OXIDATIOJS". 39 acetic acids, whilst water is also formed. In other cases oxygen is simply added on to the substances ex- posed to its action, aldehyde becoming in this way acetic acid, C2H^o + o = 0,Hp2. As with hydration, so also with oxidation, it may be said that the milder the means resorted to, the more closely allied are the products to the original parent molecules. The remarkable thing to be noted here, however, is, that w^hereas out of the body it is difficult to make air or oxygen itself effect certain decompositions, stronger reagents being required, yet, in the body, oxygen is the only substance which is utilised for pur- poses of oxidation. There is this difference to be observed, which throws some light upon this curious fact, viz., that the substances which undergo oxidation in the body are probably the simpler molecules which have been first produced from larger molecules by hydration ; these larger molecules, being for the most part colloidal in nature, offer, as a rule, less resistance to processes of change than substances of a crystalline character, to which class most of the substances treated in the labora- tory belong. Moreover, the simpler nuclei, which undergo oxidation within the body, may be in statu nascendi, that is to say, just broken off from the parent substances, and scarcely settled down into their next forms, and it is notorious that bodies in this state of being are peculiarly liable to undergo oxidation under given conditions. No doubt, within the body these processes of hydra- tion and oxidation may occur successively so quickly as practically to occur together, or they may even literally occur together. We have an example of this in the 40 GENERAL. laboratory with acetylene, which, under these combined influences, becomes acetic acid, It is too often ignorantly imagined, and also stated sometimes, that the animal function is mainly or entirely one of analysis. The act of synthesis is conceived to reside almost exclusively in life of a vegetable character. This is erroneous, for we find most complicated syn- thetical acts going on in the animal body itself, and surely the very existence of brain matter and haemato- crystalline is sufficient proof of this. To appreciate the truth of this it is only necessary to bear in mind that life can be sustained upon food made up of albuminous com- pounds, fat, starchy matters, sugar, and water ; and hence it must be by reactions occurring between these sub- stances, or the products produced from these within the system, that the brain-matter and other principles are evolved. Not only is it so with brain principles, but also with many of the constituents of the bile and the blood, &c. But of the exact processes by which such syntheses are effected, we may be said to know next to nothing. One of the most evident of these synthetical acts is the formation of the solid tissues themselves, mainly composed as they are of albumin in one or Other form. Fibrin, or the flesh of animals, when eaten as food, suffers a kind of analytical change in the stom.ach ; it is changed, as we know, into soluble peptone-substance, which, by its solubility and ultimate state of division, admits of being absorbed into the circulating fluids of the body. By and by, however, the peptone-substance is synthetically changed into solid albumin "again, and, as such, goes to SYNTHETICAL ACTS IN THE LIVING BODY. 41 form muscle and so forth. Much more marvellous, how- ever, is the power existing in the protoplasm of brain matter — the power by which those constituents of the blood which are requisite are selected, and combined to make the solid principles entering into the brain compo- sition. One can conceive that this selective power seizes hold of a fat or similar principle, together with a suitable form of phosphoric acid, and also neurine, and these substances being thus more intimately brought in con- tact, they, through the synthetical influence residing in the protoplasm, combine, giving rise to those compli- cated substances with whose chemistry we shall else- where make ourselves familiar. Allowing that the lai'ger number of principles met with in the living body are excretory ; that is, products of analytical or destruc- tive change, there yet remain a scarcely inferior number of other principles which, as they do not exist in our food, must be regarded as the products of synthesis or construction elaborated in the body itself The proper pursuit of chemical enquiry has taught us somewhat of these various processes and products, and will in its perpetuation yield much more — almost an un- limited amount of information. It will be seen that the researches of chemists — such as those of Schiitzenberger — directed upon albuminous bodies, have thrown much light upon what may be called the excretory power in life, so that we may say with tolerable certainty, that this and that constituent of the urine have been derived from the decomposition of albu- min. So in the future, as this sort of knowledge shall increase, we may possibly be able to trace back all excre- tory substances, not only to their parent molecules, but 42 GENERAL. also to indicate the very processes which have led to their production. Schiitzenberger's method of procedure was one em- ployed beforehand by Strecker in many of his investi- gations, and is the same as that employed by Thudichura in his study of the constitution of brain principles. And this method is a proper method, because it is in imitation of that natural hydration process incessantly going on in the Hviug body. But it has been shown that oxidation by air also occurs within the body, and hence it is reason- able to expect that researches having for their object the study of the mild oxidising power, or that united with one of hydration, as applied to albuminous and other principles, woidd lead to even more important infor- mation than any of which mankind is now in possession. The blood may be viewed as a solution containing a variety of substances exposed to the action of dissolved and combined oxygen ; a similar process is going on at every point of the body reached by the blood currents. Hydration is also going on here and there, if not every- where, and the two processes often together. What wonder, then, that the multitude of substances thus elaborated and produced is so great. Even the sub- stances thus elaborated and produced act and react, and thus the number is increased till it becomes almost end- less. It is in the power of chemists to imitate such a state of things to some extent in the laboratory, but the power is one of which they have availed themselves as yet in a very small degree. Who can tell, for instance, what results might be obcained by studying the action of oxygen or air upon peptones, or upon the phosphorised matters of the brain, under conditions where hydration SUBJECTS EEQUIRI^'G THE CHEMIST's STUDY. 43 could not obtain, and also under other conditions where this process may precede or accompany that of oxidation? Such studies would probably throw much hght upon the relations existing between bodies found in the blood, the brain, the bile, and the urine, and it is principally upon a perfected knowledge of such relations that we can hope for a philosophy of chemical physiology to be constructed. At present there is no such philosophy, but only a number of oases of facts, between some of which certain probable relations are dimly visible. But the connection is broken at almost every point, and thus we are left with a semi- rational view of life, and a less rational art of medicine. PART II. ORGANS, FLUIDS, AND PEOCESSES CONCEENED IN DIGESTION, &c. MIXED SALIVA. 47 CHAPTER ly. SALIVA AST) ORAL DIGESTION. Befoee entering upon the study of foods and the nature of those best quahfied to meet the demands of the system, it will be best to consider what those demands are, and the methods by which food is assimilated in the body. Mixed Saliva and Oral Digestion. — The food is com- minuted in the mouth by chewing, and at the same time it becomes mixed with the saliva — a mixture of fluids secreted by different sahvary glands (the ducts of which discharge into the cavity of the mouth), and buccal mucus, or the secretion of the mucous membrane of the oral cavity, containing some few epithelial particles. Mixed human sahva is a turbid, opalescent, and somewhat viscid fluid, having a specific gravity of 1-004 to 1'006 generally; its specific gravity is very hable to variations, being dependent upon the amount of admixed mucus, and it not rarely rises as high as 1-025. According to Wright, saliva is denser after partaking of food than when observed under fasting conditions. It may be obtained in quantity by tickling the fauces with a feather. As thus obtained it presents a more or less alkaline reaction to test paper, and has the power of transforming starch into sugar, as first shown by Leuchs. This power possessed by ptyalin, as the active prin- ciple of saliva is termed, resembles that of diastase, a 48 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. ferment produced from malt, and one wlii eh Baron Liebig applied in the fabrication of a food for infants. Although we are unacquainted with the chemical identity of ptya- line, its action upon starch so far resembles that of many ferments and dilute sulphuric acid, in that it consists in determining the molecular addition of water to starch, thereby producing sugar. In a paper by Lefberg and Georgieski,^ it has been shown that all starches are not affected alike. Thus potato-starch is converted more easily than wheaten starch, while maize-starch occupies an intermediate posi- tion ; soluble starch behaves Hke potato-starch. Starch, as is well known, consists of an outer coating of cellulose enclosing alternating layers of granulose, and although these bodies present the same empiric composi - tion, there is a considerable difference of property betrayed by the two. Thus granulose is immediately coloured blue by iodine, whereas cellulose does not exhibit this reaction until it has been first exposed to the action of sulphuric acid or zinc chloride. Similarly, in the action of saliva upon starch it is the granulose which is first converted into dextrine and sugar, and only after some time, or at higher temperatures, is the cellulose likewise altered. Of these specific changes, however, we shall have more to say in another place. Ptyalin may be isolated in a measure, though not in a pure state (probably), by precipitating fresh saHva with phosphate of lime produced in situ, that is, by the addition of phosphoric acid and Hme water. In this way 1 Bull Soc. Chim. [2] xxv. 393. PTTALIN, AND ITS ISOLATION. 49 the ferment is carried down in a mechanical manner with the calcic phosphate, and may be afterwards extracted by water. From the aqueous solution it is precipitated by alcohol, and by continually repeating the solution in water and reprecipitation by alcohol, ptyalin is obtained in a snow-white form ; its composition has not yet been determined. As it fails to give the xanthoproteic reac- tion with nitric acid, it is not regarded as an albuminoid, although it is not improbably derived from some such substance. Its solution does not coagulate on heating, but its fermentive power is destroyed at 60°; it is also destroyed by strong acids and alkalies, and does not take place at 0°C. Ptyalin is most active at 40°C. Besides ptyalin, mixed saliva contains, as we have seen, mucus, a small quantity of undetermined fat or fatty acids, potassic and sodic sulphocyanides, calcium, and alkaline carbonates. According to E. Bottger,^ he has obtained indications of the presence of a nitrite in saliva by acidifying with sulphuric acid, and adding a mixture of cadmium iodide and starch, when a blue colour is said to be produced. The presence of sulphocyanogen in saliva is peculiar to man, and its function remains unexplained, although one author (Kletzinsky) has suggested that its presence resists the formation of fungi between the teeth. A tooth-brush would do this as well ! Sulphocyanides are recognised in saliva by the red colour which ferric chloride imparts to it, or to the distillate obtained by boihng it with acids. This colour disappears on adding mercuric chloride, and thus distinguishes it from that given by meconic acid. 1 aiem. Centr. 1872, 741. E 50 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. E. Bottger^ recommends, in preference to tins test, to impregnate a strip of Swedish filter paper with tincture of guaiacum, dry, and afterwards pass through a solution of cupric sulphate (1 in 2000) ; paper thus prepared instantly turns blue when moistened with saliva. Wright found the quantity of sulphocyanides to increase under medicinal treatment involving consumption of sulphur. Calcium exists in combination in saliva other than as carbonate, perhaps with ptyalin, for if it be allowed to stand in the air, a crust of calcic carbonate forms over the surface ; it is not improbable, however, that it exists as bicarbonate. The deposits of so-called tartar, which frequently are allowed to form upon the teeth, consist of calcic carbonate which is derived from saliva. Magne- sium is also found in saliva, and traces of phosphoric acid, alkaline chlorides, carbonates, and sometimes sul- phates, but their proportions, as also those of the other constituents, are by no means constant. Lehmann deter- mined the fixed solids in mixed saliva at 0-388 to 841 per cent. ; frequently, however, 1-5 per cent, is found. Ptyalin constitutes about one third of the soluble solids of saliva. The follo\ving analysis of mixed saliva ^ exhibits its general composition ' Ptyalin =1-4 Water 994 Mucus =1-5 SoUds 6 - Fat =1-3 = 1000 Sulphocyanides = 0-1 I Salts =1-7 Besides the previously enumerated constituents of ^ Zeitschr. Anal. Chem. xi. 350. "^ Taken from Ralfe's Physiological Chemistry, where source is not stated. CONSTITUENTS AND FUNCTIONS OF SALIVA. 51 saliva, albumin is invariably present in small quantity in the respective forms known as globulin and mucin. As hereafter we shall consider albuminous principles at some length, we need not refer more particularly to them in this place. The part taken by saliva in the great process of digestion is not thoroughly known, but there can be no doubt that one of the most important functions of saliva is exerted through the power of ptyalin to convert the starchy matters contained in food into sugar, as already described. It has been pretty well ascertained experi- mentally by Lehmann and others, that there is scarcely time for this process to complete itself in the mouth ; it is continued in the stomach and the smaller intestine. Saliva serves also to moisten the food, and thus it facilitates the act of deglutition ; this is, of course, an im- portant point, and from what we know, it appears to admit of experimental confirmation by the fact that dry foods cause a more abundant flow of sahva than wet foods or liquids. Liebig suggested, from the frothy nature of saliva, and the fact that it occurs full of air bubbles, that one of its purposes was to convey air to the stomach and intes- tinal canal. All that can be said, however, in favour of this view is that it has not yet been determined whether the presence of air is essential to the transformation of starch into sugar by means of ptyalin; probably it is not. The quantity of mixed saliva secreted by a man in 24 hours varies between 300 and 1500 grammes ; it is increased by excitants and certain medicines and poisons. Particular Salivary Secretions. — There are four kinds e2 52 ORGAN'S, FLUIDS, ETC., CON'CKRNED IN DIGESTION. of salivary glands, and the secretion furnished by each of these is distinct in character.^ The sublingual gland lies underneath the tongue, ^vhile the submaxillary glands are situated on the sides of the tongue underneath the lower jaw; all these glands, however, discliarge into the same duct, which lies under- neatli the forepart of the tongue. From these and the parotid glands the saliva is collected by the introduction of canulce into the ducts, but the secretion of one and the same gland or set of glands ma}' vary according to the acrencies which call them into action. For these reasons and the difficulty attached to the operation of collecting saliva, the chemical nature of the secretions of distinct glands is but little known. Four different kinds of secretion, however, are recognised, according to the nerves whose irritation has furnished the supply. Chordal saliva is secreted by the submaxillary glands on irritation of a nerve which is a brancli of the facial, and is termed ' chorda tympani.' Its composition is described by Thudichum as follows : — ( =1-5 Globulin, mucin, and coagulable albumin. Solid matters = 4 per cent.. ^2-5 mainly alkaline chlorides and lime I salts (chiefly bicarbonate). Sympathetic saliva is furnished on irritation of the sympathetic nerve, and is collected from the submaxillary cflunds. It is opaque and tough in character, contains from 15 to 28 per mille of solids and much free alkali. Ganglionic saliva flows when the submaxillary gan- 1 Lehmann's Physiological Chemistry, vol. ii. Also Thudichum's Physio- loyical Chemistry. PATHOLOGICAL ASPECTS OF SALIVA. 53 glion is made the centre of a reflex action working by way of the lingual nerve. Paralytic saliva is very thin, and contains but little solid matter ; it results under the influence of nervous paralysis, caused by degeneration, or poisoning, or wounds which separate the secretory nerves. Nothing- is known of its composition. Parotid saliva is alkaline and viscous, and has the following composition in 1000 parts : — Water =995-3 Organic matter — ptyalin, albumin, globulin . =1*4 Calcium carbonate . . . . = 1"2 Other mineral matters . . . . = 2"1 inoO-0 Pathological Aspects of Saliva. — The presence of lactic acid in saliva has been frequently asserted, but while there is great doubt about it, it is certain that during some diseases the saliva grows more or less acid ; thus, according to Donne,^ saliva is acid in inflammatory aflections of the primse viae, in pleuritis, encephalitis, &c., &c. Wright assumes the acid state sometimes observed in saliva to be referable to, among other diseases, rachitis. But all these and many similar observations are not worth much credit, being too vague, and admitting of no reduction to definiteness. It is also said that lactic acid is to be found in saliva in cases of diabetes, but the state- ment has as often been contradicted. In salivation pro- duced by mercury, the sulphocyanides ordinarily present disappear from saliva, and mercury appears. Many medicinal preparations, such as potassic iodide ^ Histoire physiol. et -pathol. de la Salive. Paris, 1836. 54 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. and chlorate, readily pass from the blood into the saliva, nnd may be detected there long before they appear in the urine. Leucine has been found in tlie paralytic sahva of hysteric persons, and in other diseases the presence of urea has been stated ; this is not surprising, lor in cases of cholera it appears in quantity in the brain also. According to Wright, biliary matters, and especially cholesterine, sometimes even pus, pass into the saliva, but Lehmann viewed Wright's work on saliva with considerable suspicion. Some of his work is, how- ever, of no mean value ; and, among other matters, he states that he was led by experiment to lend confirmation to the old opinion that the saliva of enraged animals, or men during violent anger, is capable of inducing sus- piciously morbid symptoms when introduced into the blood. Later experiments by Lehmann and Jacu- bowitsch have not supported the results obtained by Wrio;ht, although, as is well known, saliva is the carrier of the contact ferment-poison by which hydrophobia is propagated. GASTRIC JUICE AND ITS CHAEACTEES. 55 CHAPTEE V. GASTRIC JUICE AKD GASTRIC DIGESTION. Resume of Gastric Digestion. — The food, reduced to a pulp in the mouth and mixed with saHva and air-bubbles, arrives in the stomach and there undergoes what is termed gastric digestion. The mucous membrane lining the walls of the stomach is covered with multitudes of simple glands which open upon its surface, and among these there occur others which are more complicated, and have their blind ends subdivided. These latter are the peptic glands, which are excited by the presence of food in the stomach to excrete a thin acid fluid, called the gastric juice. The contractions of the stomach roll the food about and thoroughly incorporate it with this said juice, forming, in process of time, a matter of consider- able consistency called chyme. Description and Characters of Gastric Juice. — Gastric juice is an acid, glairy, shghtly yellowish fluid of varying specific gravity, according to the means adopted for causing its flow and the relative time of collecting it to that when food was last in the stomach, &c. At early stages in the process of digestion it has a specific gravity of I'OIO. It does not become turbid on boiling, and has no great tendency to putrefaction. Its composition, which is no doubt not a constant, has been variously given. 56 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. Thus Sclimidt,^ who made an analysis of a sample obtained from a woman suffering from gastric fistula, assigned to it the following constitution: — Specific gravity 1'020 Water = 954-13 Pepsin = 0-78 Sugar, albuminates, lactic and butyric acids, ammonia, &c = 38-43 Potassic chloride = 0-70 Sodic cliloride = 426 Potash = 0-17 Calcic phosphate ...... = 1-03 Magnesic phosphate = 0-47 Ferric phosphate = 0-01 From the presence of sugar, albuminates, &c., it will be seen that this analysis refers to gastric juice mixed with food which has been to some extent previously altered by saliva. This probably explains wdiy the fluid thus examined was slightly alkahue, a result which would be brought about by the presence of saliva. This is confirmed by the fact that when the gastric juice was made to flow by introducing peas into the stomach, it was obtained unmixed with saliva, and containing free hydrochloric acid. The amount of gastric juice secreted daily by the human stomach has been variously estimated. Gruene- waldt^ estimated it at 264 grms. for every kilogramme of body weight, or about 31 lbs. in twenty-four hours. Other determinations lead only to about 10 per cent, of the body weight, or 16 lbs. Schmidt determined the amount of free hydrochloric acid in dogs' gastric juice at from 0*245 to 0-423 per cent., and also found traces of chloride of ammonium. ' Lehmann's Physiological Chemistry, vol. 3, AppendLx, p. 503. ^ Sued yastrici humani Indoles physica et chemica, ed. Dorp. Li v. 1853. , THE COMPOSITION OF GASTRIC JUICE. 0/ L. Rabutem and F. Papillon^ have demonstrated the presence of hydrochloric acid in the gastric juice of the ray, and a metallic bromide, but no hydrobromic acid. Mr. Ealfe,^ without naming the source of his analysis, gives the following composition to human gastric juice. Specific gravity . , . . . . . 1-0010 Water = 97600 Organic matter and pepsin . . . . = 15-00 Free acid . = 4-78 Sodium chloride = 1'70 Potassic „ = 1'08 Calcic „ = 0-20 Ammonic „ = 0'65 Calcic phosphate = 1*48 Magnesic „ = 0*06 Ferric „ = 0-05 Thudichura expresses^ the composition of this juice as follows : — (1) Water 994-6 (2) Solid and permanently fluid ingredients, other than water 5*39 (3) Contains pepsine 3"0 Hydrochloric acid 0-2 Perhaps a little lactic acid. Chlorides of the alkalies. Phosphates of the earths. Ch. Eichet, in some observations* upon digestion, made through the agency of a gastric fistula, points out that the mean acidity of the gastric juice, whether pure or mixed with food, is nearly equivalent to 1'7 grm. of hydrochloric acid per 1000 grms. of liquid. The highest 1 Compt Rend. Ixxvii. 135-138. ^ Ralfe, Physiological Cliemistry, p. 128. ^ Thudichum, Chemical Physiology, p. 10. * Compt, Rend. Ixxxiv. 450, 452. 58 ORGANS, FLUIDS, ETC., COXCERNED IX DIGESTIOX. acidity observed was 3'2 grms., and the lowest 05. It appears, also, according to this author, that the acidity is not influenced by the quantity of fluid in the stomach, but is invariable, or almost so, whether the stomach be empty or full. The acidity is increased by alcoholic drinks, but diminished by cane-sugar. When acid or alkaline liquids are injected into the stomach, the gastric juice reassumes its normal acidity in about one hour. The gastric juice is more acid during digestion, and the acidity increases with the digestion. M. Ch. Eichet comes also to the conclusion that hunger does not result solely from emptiness of the stomach. Before going further, it should be stated that inas- much as the juice examined has been mainly obtained from persons sufiering from fl'stulas, or from dogs upon whom fistulas have been produced by certain operations, it is difficult to say how far the analyses are to be re- garded as representing normal gastric juice or morbid juice. These studies, however, led to the formation of what is termed artificial juice, and most of the properties possessed by gastric juice have been ascertained from a study of this preparation. We shall consider this matter further presently. For the moment, we may view gastric juice as a fluid containing dilute hydrochloric acid, and a ferment termed pepsin. Function of Gastric Juice. — Together, these sub- stances have the power of dissolving otherwise insoluble albuminous substances, such as white of egg, fibrin, casein, gristle, gluten, &c., thereby yielding thick turbid solutions of what are called peptones. Connective tissues are not so readily attacked by gastric juice, and fats do not appear to be altered by contact with it. FUNCTIONS OF GASTEIC JUICE : PEPSIN. 59 By being rendered soluble, the food henceforth becomes assimilable by the blood system, and the pro- duct, or chyme (a solution of peptones mixed with saliva and saccharine matter resulting from the action of saliva upon starchy matters) is, to some extent, absorbed by imbibition through the walls of numerous delicate vessels which convey it from the stomach to the blood, and thence to the vena portas. This absorption is no doubt effected by a process of dialysis. These peptone solutions, unlike albumin in its ordinary forms, easily dialyse through parchment paper. Part, however, of the chyme escapes through the pylorus and enters the duodenum, where a distinct kind of digestive process is carried on. This will be considered in another chapter. Let us here consider more fully the nature of the con- stituents of gastric juice and their functions. Nature of Pepsin. — Pepsin may be isolated by the same method described already for isolating ptyaline, viz., by its adhesion to phosphate of lime precipitated in situ. It may be also prepared by macerating the mucous membrane of the stomach of a recently killed animal (rejecting the pylorus) in dilute phosphoric acid. It is in this way dissolved, and the solution, on precipitation with lime water, yields a precipitate from which the pep- sin may be extracted by glycerine. Another method consists in the re-solution of the phosphate precipitate in very dilute hydrochloric acid and addition to this of a saturated solution of cholesterine, consisting of 1 part ether and 4 of alcohol. This latter is best added down a thistle funnel, and the whole mixture well agitated. The choles- terine thus separates, and as it rises to the surface it CO ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. attaches the pepsin to itself in a mechanical manner. The cholesterine may be subsequently removed after fil- tration, by means of ether, and tolerably pure pepsin i» thus left behind. Although pepsin is a ferment evidently of albuminous origin, it is not ordinarily considered as a form of albu- min, and mainly because it does not yield the xantho- protein reaction {see Albumin) with nitric acid. In a subsequent place, however, it will be shown that it possesses undoubted relations to albuminous substances. Pepsin is not itself destroyed during digestion, and thus far its functions appear to belong to what are termed ' contact actions ; ' that is to say, it is able to re- solve large quantities of solids into a soluble form in the presence of dilute acids — more particularly at 40°. This action is well exhibited by exposing some pieces of coagulated white of egg to a faintly acid solution of pep- sin; they are speedily and entirely dissolved. When, however, the liquor is saturated with peptones it ceases to act, just as yeast ceases to cause fermentation of sucrose solutions when the percentage of alcohol rises above a certain extent. An addition of acid fluid enables further digestion, however, to take place. As is well known, pepsin occurs now in various commercial forms, and is extracted chiefly from pigs' stomachs. Pepsin may be obtained in the form of a greyish powder by precipitation ; it is insoluble in alcohol and ether, but very soluble in dilute acids and glycerine. Its solutions are precipitated by alcohol, and coagulated by boiling; once boiled, its solutions lose their power of digesting, and the same ability is destroyed by a neutrali- sation of the acid solutions. Aqueous solutions of pepsin THE ACID OF GASTRIC JUICE. 61 are precipitated by corrosive sublimate, by lead salts, and by solutions of tannic acid. The Acid of Gastric Juice. — The nature of the acid in the gastric juice has been the subject of much dispute. Blondlot maintained that it consisted of phosphoric acid existing as acid phosphate of calcium. Others have re- garded the acidity of gastric juice as due to the organic acids contained in or developed from the food by means of pepsin and ptyalin. Yet others have asserted the acidity referable to the presence of lactic acid, many investigators having again and again detailed the means whereby they have established the presence of that acid, and others denying this statement on experimental data with equal enthusiasm. The matter appears, therefore, to be still somewhat unsettled so far as the normal occur- rence of lactic acid in gastric juice is concerned. This lactic acid has been supposed by some to be formed from carbohydrates by the action of ferments. Lehmann and others state to have found lactic acid in gastric juice, while Schmidt and Maly failed in their attempts to identify it. One thing, however, has gradu- ally become matter of certainty, that the main acidity of the gastric juice is due to free hydrochloric acid. E. Maly^ has recently made an investigation of the source of the acid of the gastric juice, the details of which are not without interest, confirming as they do in a singular manner the hypothesis first advanced by Thu- dichum, and described later on. Maly wished to find out whether the hydrochloric acid was derived from the dissociation of neutral chlorides or from their decompo- 1 Ann. Chem., clxxiii. 227-273. 62 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. sitioii by lactic acid formed from carbohydrates. From a numerous series of experiments upon dogs, he arrived at the conclusion that the source of the free hydrochloric acid is to be sought in the dissociation of chlorides with- out the aid of an acid ; and further, that the formation of lactic acid from carbohydrates is not a function of tlie living membrane of the stomach. Incidentally, several important facts were demonstrated ; first, that chlorides of sodium distilled with lactic acid yielded traces only of hydrochloric acid towards the end of the operation ; and, secondly, that when lactic acid was allowed to diffuse in presence of ferrous, sodium, calcium and magnesium chlorides, free hydrochloric acid was produced. In a series of experiments with the mucous mem- brane of pig's stomach, he found that at 40*' with 2 per cent, solutions of grape-sugar, cane-sugar, milk-sugar, and dextrin, lactic acid was formed; but he views this result as due to the presence of a special organised body, and not a soluble chemical ferment. Interesting as these experiments are, they leave a margin for doubt, but we pass on to consider Thudichum's hypotliesis above alluded to. The Function of the Acid. — Thudichum ^ assumes that in the walls of the stomach, chloride and lactate of sodium are split up into the free acids and caustic soda ; in tliis way the decomposition of salt would be repre- sented thus, NaCl + H20=NaH0-l-HCl. But inasmuch as we never meet with caustic soda in the animal economy, at first blush the above idea would appear to be nega- tived. Thudichum, however, supposes that before the ' Chemical Thysiology, pp. 14 and 15. CHYME AND PEPTONES. 63 soda enters the blood it has a distinct function to per- form, and that is the protection of the stomach against the corrosive action of its own excretion. Under certain abnormal conditions this corrosive action really obtains, and gives rise to gastric ulcer and other pathological processes. In the blood Thudichum supposes that the caustic soda is converted into carbonate, and passing through the gastric veins into the portal, enters the liver. There its function is completed, but its consideration must be left until we come to study bile and its influence upon the process of digestion. General Characters of Chyme and Peptones. — As above stated, the product of stomachic digestion is chyme, con- taining starch, sugar, fat, and peptones (if both carbohy- drates and animal matters have been eaten). It appears also that there are present a number (five or more) of albuminous substances more or less closely related on the one hand to peptones, strictly speaking, and on the other hand to unaltered albumin. It is probable that these but represent the various phases presented in the gradual change of ordinary albumin under the influence of hydrochloric acid and pepsin. The peptones, ciu-iously enough, mainly agree in general composition with the original matters from which they are produced, a result which shows that the change is more of an intermolecular nature than a sphtting-up. Peptone solutions are not coagulated by boiling, but are precipitated by absolute alcohol. With nitrate and nitrite of mercury they give Millon's reaction ; optically, they turn the plane of polarisation towards the left. The Specific Nature and Actions of Pepsin. — Liebig showed many years ago that if albuminous matters were 64 ORGANS, FLUIDS, ETC., CONCERNED IX DIGESTION. SO exposed to air and moisture as to undergo partial putrefaction, even if to a very slight extent, the whole would liquify and become a diffusible fluid of a composi- tion agreeing with that of the original unclianged matter. That is to say, in the change of a minute fraction some sort of ferment or agent is generated which has the power of acting upon tlie remaining quantity as pepsin acts on albumin. Moreover, Liebig said what we call pepsin is but a part of a mucous membrane which in its own particular composition is identical witli those albu- minous princii)les whose properties are changed by con- tact with it ; in fact, said he, the tendency to change inherent in the Hving tissue is communicated by contact to those similar but non-living matters outside. In the present day science has no better explanation than this to offer. In another place we give an account of some re- searches of Alex. Schmidt and of Erlenmeyer, which, taken in conjunction with the work of Schlitzenberger, promise to throw much light upon the general nature of chemical ferments in the human body, and their relation to that form of matter ordinarily called albumin. Abnormal Constituents of Gastric Juice. — Very Httle is known regarding the pathological phases of gastric juice. In cases of gastric catarrh the mucus of the stomach ap- pears to accumulate to an abnormal extent, and to induce processes which result in the formation of acetic, butyric, and lactic acids, thus increasing the normal acidity of the stomach. In uraemia, or after extirpation of the kidneys, urea is said to be secreted by the gastric glands. GENERAL CHAEACTERS OF BILE. 65 CHAPTEE VI. THE BILE ; PANCREATIC, INTESTINAL, AND SPLENETIC JUICES ; INTESTINAL DIGESTION AND F^CES. It has been shown in the last chapter, that while yet in the stomach a certain quantity of the chyme under- goes direct absorption into the blood system. Another part, however, passes through a further process called duodenal digestion, where bile and pancreatic juice play a prominent part. Before proceeding to the study of this and intestinal digestion, it is proposed to make our- selves acquainted with the general nature and properties of these fluids, beginning with the bile. Among the functions of the liver the most important is its secretion of bile ; it has other functions, whose study, however, is best postponed for a time. General Characters of Bile. — Bile is one of the most comphcated secretions of the human body, and has a most important chemistry. It accumulates probably continuously, but is expelled during digestion from the gall-bladder wherein it is stored, and a further quantity escapes during the emptying of the stomach. As taken from the gall-bladder, it often receives the name of gall or cystic bile ; and when warm smells like musk. It constitutes a viscid liquid of a yellowish-green colour, but which becomes strongly yellow on dilution ; it is heavier than water (sp. gr. 1"02), and owes its viscidity to the p 6G ORGANS, FLUIDS, ETC., COXCERXED IX DIGESTIOX. presence of a quantity of mucus derived from the gall- bladder. Until this mucus be removed, bile exhibits a tendency to undergo putrefactive change, but if the mucus be removed by dilution, addition of acetic acid (thereby producing coagulation), and filtration, it is readily preserved. Human bile has been studied, but not so intimately as ox bile, the former being obtained only from fistulous openings, whereas there is no difficulty in obtaining that from the ox ; this is of a green colour. Tlie following analysis given by Berzehus ^ is useful as representing, in a general way only, the composition of ox-bile. Water 90-44 Biliary and fatty bodies 8"(X) Mucus 030 Watery extract, chlorides, phosphates, and lactates . 0-48 Soda 0-41 The composition presented by the bile of various animals has been shown by Strecker^ to difier only in the varying proportions in wliich two of its constituents (taurocholic and glycochohc acids) exist therein. Thus he has stated that the bile of the dog is almost free from the sodium salt of glycochohc acid, without regard to the nature of the food ; while the bile of the sheep, and that of the goose (Marsson), contains chiefly taurocholate of sodium also. The bile of the pig is characterised by hyocholic acid. Somewhat chfierent estimates have been given of the amount of bile secreted in the human body, one fixing it at 1200 grms. per day, while others give varying quan- 1 Miller's Chemistry, Part iii. [1867] p. 883. « Ann. de Chem. mid Pharm., Bd. 70, S. 140-198. QUANTITY AND COMPOSITION OF BILE. 67 tities from about 30 to 800 grms. per 24 hours. Bile appears to be most actively secreted shortly after eating, when the solids constitute about 5 per cent. ; these in- crease up to about 10 per cent., and then decrease again to 5 per cent, during fasting. The quantity secreted by each animal seems to be pecuhar, and not to bear any definite relation either to the body weight, or, as Thu- dichum suggests, to the size and weight of the liver, but rather to the size and weight of the hver in relation to the weight of the blood, since, as we shall hereafter see, it is from this fluid that the liver elaborates the bile. It is a curious fact that most of the salts found in the bile of salt-water fishes have potassium as their base, while the bile of fresh-water fishes contains chiefly sodium salts. Most of the literature relating to the chemistry of the bile is without value ; Strecker's researches stand out, however, from the others before and since in a remark- able manner, and it is to his work that we owe most of our knowledge regarding its composition. Bile, then, contains taurocholate and glycocholate of sodium (resi- noid salts), and a number of colouring matters, the chief of which are bilirubin and bihfuscine ; a third colouring principle is termed biliprasine. Bile also contains leci- thine, chohne, and cholesterine, but is free from albumin. Ox bile is also said to contain a small amount of stearic, oleic, and lactic acids, in combination with potassium and ammonium. As bilirubin occurs in bile, it a]3pears to exist as lime salt, the brown granules of which may often be observed while examining bile microscopically. Phos- phates of sodium, calcium, and iron, sodic chloride and traces of copper, are also contained in bile. f2 OS ORGANS, FLUIDS, ETC., COXCERNED IX DIGESTION. 0. Jacobsen,^ in an analysis of the ash of bile obtained from an abscess, found the following quantities in 100 parts of dog bile — KOI 1-276 NaOl 24-508 Na.,C()3 4-180 NagPO^ 5-984 OaalPOJj 1-072 C. G. Lehmann^ claims to have demonstrated tlie presence of preformed alkaline carbonates in ox bile. Thus in one experiment he found 00046 per cent., and in a second 0"1124 per cent., normal sodic carbonate. This fact has a very important bearing upon our views of the great process of digestion, and is particularly in- structive when viewed in connection with Thudichum's hypothesis regarding gastric digestion. Biliary concretions, when they occur in man, consist of cholesterine, colouring matters, earthy salts, and other principles not so well ascertained. Corresponding con- cretions are liable to occur also in other animals. THE PANCREAS AND THE PANCREATIC JUICE. The pancreas is constructed in the main of albu- minous substances, but it contains also a considerable quantity of leucine, xanthine, hypoxanthine, and guanine. The ferments, to which further allusion will be made under pancreatic juice, may be extracted from it by suit- able means. The function of its secretion is entirely confined to the digestive processes. Its nature has been studied upon » Deut. CTiem. Ges. Ber , vi. 1026-1029. ^ Lehruann's Phys. Chem,, vol. ii. p. G7. Euglisli Translation. COMPOSITION OF PANCEEATIC JUICE. 69> the juice obtained from temporary or permanent fistulas, while the properties of the ferments contained in it have been ascertained by isolating them in an impure form from the pancreas itself. General Characters of Pancreatic Juice. — Pancreatic juice is a more or less tough, viscid secretion of alkaline reaction, and having a specific gravity of from 1-008 to 1*009, or somewhat greater. It contains from 10 to 11 per cent, of sohds, and is peculiarly liable to putrefactive change after removal from the body. According to Ealfe's 'Physiological Chemistry,' its composition is as follows : — Water 900-76 Organic matter ...,...,. 90" 38 Sodium chloride 7'36 Free alkali 0-32 Sodium phosphate 0-45 „ sulphate 0"10 Potassium „ ....... 0*02 Oomhinations of lime 0*64 „ magnesium . ... . . 0'05 „" iron 0-02 The organic matter of pancreatic juice contains soluble albumin and alkali-albuminate, ferment mat- ters, and often small quantities of fat, leucine, tyrosin, butyric acid, &c. According to Gmehn and Tiedemann, it sometimes contains as much as 4 per cent, soluble albumin, and it is not unlikely that this exists as an intermediate formation to be afterwards elaborated into ferment matters, or which has resulted from the action of the ferments upon fibrin. Kiihne states that the prolonged action of pan- creatic ferments upon peptones leads to the formation of leucine and tyrosin ; and, as we shall see in a future chapter, these bodies are known to result from a certain TO ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. decomposition of albumin. Basil Kistiakowsky^ has also observed that by the action of pancreatic juice on fibrin, leucine, tyrosin, and glutamic acid result. S. Eadzie- jewski and E. Salskowski,'-^ in the same process, have observed, moreover, the production of aspartic acid (viz., by digestion of fibrine at 40-50°). Although from time to time statements have been made relative to the isolation of the pancreatic ferments, yet so far as can be judged, they have never been isolated as chemical individuals, but always in a form associated more or less Avith foreign matters. Some writers speak of the existence of tliree ferments in pancreatic juice, and Dauilewsky has affirmed that he has separated two of these. Such preparations are obtained by various methods, the best of which is that recommended by Wittich, which consists in reducing the pancreas of the ox to a mince- meat, hardening by standing in alcohol for 24 hours, and extraction by glycerine. From the filtered extract, alcoliol precipitates the ferment-matter. In a more im- pure form it may be isolated also by rubbing down ox pancreas with sand or broken glass, extraction with water, and precipitation of the extract with alcohol. Of the amount of pancreatic juice secreted, many various estimates have been made, but little reliance can be placed upon them, since the observations have been effected under more or less deranged physiologi- cal conditions. From certain experiments upon dogs, Bidder and Schmidt have calculated that an adult man, weio-hincT 10 stone, secretes 150 grammes in 24 hours. 1 Pfliiger's Archiv. fiir Phjsiologie, ix. 438-459. * Dent. Chem. Ges. Ber., vii. 1050-1051. FUNCTIONS OF PANCREATIC JUICE. 71 According to Frericlis, it is only secreted during di- gestion. The pancreatic juice appears to exercise a number of fimctions, wMcli may be expressed as follows : — (a) The completion of the solution of imperfectly digested matters issuing with the chyme from the stomach ; so-called albuminoids being converted into albuminones, or substances soluble in alcohol and not coagulable by heat. (b) The emulging of neutral fats. Pancreatic juice makes perfect emulsions when agitated with neutral oils, and it was chiefly upon observations of this kind, backed up by certain physiological experiments, that Bernard came to the conclusion that one of the chief functions of pancreatic juice is to aid in the assimilation of fatty substances. Bidder and Schmidt and others, however, in more recent experiments, gave no support to these views. The emulsion of neutral fat transforms it into such a fine state of subdivision that it can pass through the pores of the mucous membranes into the chyle ducts. (c) Pancreatic juice is further supposed to have the power of splitting up neutral fats into free fatty acids and glycerine, and it appears certain that among other products of the decomposition of fatty matters, butyric acid has been well recognised. (d) It has also the property, in an intense degree, of converting starch into sugar, thus completing any change of this kind that may have been left imfinished by the saliva in the mouth and stomach. One of the few attempts that have been made to obtain precise chemical information regarding the 72 OEGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. changes undergone by albuminoid under the influences of pancreatic ferments, is by Basil Kistiakowsky (see his paper above referred to). He obtained pancreatic fer- ment matter by Wittich's process, and then investigated its action upon fibrin (from ox blood) by digesting the latter in an aqueous solution of the ferment during a number of hours. The original fibrin was not pure, yielding 0'625 per cent, ash, and on analysis it yielded numbers approximating to the formula C139H.226N37S O46. The peptone produced in the experiments described was also impure, yielding 1'186 per cent, ash, and on analysis it gave the composition CnsHassNggS Oee- Although these numbers and formulae can only be regarded as approxi- mately correct, yet this fact comes out, that the peptone contains less carbon and more oxygen than the oiiginal fibrin — a fact which may be related to the production of tyrosin, leucine, and similar bodies. A failure in the supply of pancreatic juice has been viewed as the acting cause of certain diseases in which undigested lumps of fat are stated to pass out with the faeces. In hentery, also, the pancreas appears to be affected. INTESTINAL JUICE, General Character of Intestinal Juice. — But very little is known either of the constitution or the functions of intestinal juice, although there can be small doubt that its influence upon the great process of digestion is by no means unimportant. From Frerichs's researches it would appear that Peyer's glands contribute but slightly to the formation INTESTINAL JUICE. 73 of intestinal juice, while on the other hand, Brunner's glands and Lieberkiihn's follicles are chiefly instrumental in its secretion. From what is known (and that is next to nothing), it would seem that in chemical composition the fluids secreted in the small and large intestines are identical. According to the researches of Lehmann, Bidder and Schmidt, and Frerichs, intestinal juice is a yellowish viscid, transparent, alkaline secretion, which coagulates on treatment with chlorides and sulphates of the alkalies. It has a specific gravity of about I'Ol, and contains from 2 to 2-5 per cent, solids, part of which is of a fatty nature. While Thierry and Frerichs have not succeeded in establishing the fact of any important change of food through the influence of intestinal juice, Bidder and Schmidt concluded that it behaves very much in the same manner as does pancreatic juice. These last-named observers calculated (on grounds not sufl&ciently precise or reliable, however, for absolute acceptance) that an adult man, weighing 10 stone, secretes about 300 grms. of intestinal juice in twenty-four hours. Intestinal juice would seem to combine in itself to some extent the powers both of the gastric and pancreatic fluids, for while bile and pancreatic juice interfere with the diges- tion of albuminous matters by gastric juice, such is not the case when albuminoids are in process of digestion by means of intestinal juice. It is in the small intestine, apparently, that certain diseased processes have their origin, such, for instance, as cholera, typhus, and typhoid fever, &c. 74 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. THE SPLEEN AND ITS JUICE. From a histological investigation of the spleen, Kolli- ker advanced the opinion that this organ was the seat of the solution and complete disintegration of the blood corpuscles, while it had been previously held that this organ was the seat of their formation. The opinion of Kolhker derived some support from a further study made by Ecker, but more especially from the researches of Scherer. This latter observer found in the splenic juice many characteristic decomposition products of the albu- minous and other nitrogenous matters said to include the blood pigment itself It was hence conjectured that the spleen accomplishes the destruction of those cor- puscles which are no longer able to carry out their original functions. Among other acids of the same series, Scherer detected formic acid in the splenic juice, and also in leucasmic blood. It cannot, however, be said even now that we are properly acquainted with the func- tions of the spleen, although later researches make it more probable that it is connected rather with the con- struction of certain constituents of the blood and with the processes of digestion. According to Thudichum ^ the spleen contains much blood, and hence it is difficult to procure its own juice in an unmixed state. The fresh spleen shows an alkaline reaction, but this becomes acid on standing. A water extract of the spleen contains liEematocrystallme, albumi- nous matters, cholesterine, hypoxanthine, xanthine, and uric, lactic, succinic, formic, acetic, and butyric acids, leucin, and inosite. ^ Chemical Fhysiolojij (Longmans & Co.), p. 49. THE SPLEEX : ITS JUICE A^'D FUJsCTIOKS. 75 Professor Schiff has recently published an important paper ^ upon the functions of the spleen, in which he shows that extirpation of this organ has no durable in- fluence on the absolute or relative quantity of the white or red corpuscles of the blood. During stomachic di- gestion the spleen prepares the ferment which, entering with the blood into the tissue of the pancreas, transforms in this gland an albuminoid substance into pancreato- pepsin or trypsin, or, in other words, into a substance capable of digesting albuminous foods. After removal of the spleen the pancreatic juice loses its digestive in- fluence upon such special substances, but otherwise re- tains its digestive properties. Although it is therefore evident from Schiff's and other researches that the spleen is actively employed in life, it yet appears that animals from which it has been removed by operation continue to live without any great disturbance. Thudichum points out that in leucocythsemia the spleen is frequently large, and weighs from nine to ten pounds ; when in that disease it is small, the lymphatic glands are always enlarged. Among diseases which affect the spleen one is particularly remarkable, namely, waxy or so-called amyloid degeneration. In such cases the spleen is indigestible in artificial gastric juice, and is not prone to change. Thudichum objects to the term ' amy- loid ' degeneration because the spleen in such disease gives no sugar on boiling with dilute sulphuric acid, which it would do if it contained any amyloid (starch - like) principle. M. G. Pouchet, in a recent communication to the ^ Read before the Medical Congress of Geneva, 1877. Gaz. Hebdoma- daire, Sept. 21, 1877. i ORGANS, FLUIDS, ETC., COXCERXED IX DIGESTION. Societe de Biologie, has shown tlmt in certain Selachian fislies the elements of the splenic parenchyma are undis- tinguishable from certain corpuscular elements contained in the blood, and hence he conjectures, in opposition to some views above stated, that the spleen is concerned in the genesis of the blood corpuscles. That the corpuscular elements in the blood of the fishes alluded to ultimately become transformed into red corpuscles appears beyond doubt, but M. G. Pouchet does not seem to have estab- lished this to be true of the splenic elements resembling them. INTESTINAL DIGESTION. After the completion of gastric digestion which has been already described, the chyme passes by way of the pylorus into the duodenum, and here the bile and pan- creatic juice come into play ; they flow through a com- mon aperture, and convert chyme into chyle. We have seen (in the chapter on gastric digestion) that the soda set free by the action of the stomach walls upon sodic chloride ultimately reaches the liver and combines with carbonic and certain biliary acids, forming sodium salts therewith. Now the first action of the bile, as it mixes with the chyme, consists in the decomposition of these same sodium salts by the free acid of the gastric juice, and this is attended consequently with the formation, but not the precipitation, of free biliary acids. Although Marcet held that the neutral fats are split np into fi'ee fatty acid and glycerine while yet in the stomach, no adequate evidence of such a change is forth- coming. Indeed we may view the action of bile and pancreatic juice (both of which are alkaline) to be one of INTESTmAL DIGESTION. 77 saponification, the chyme assuming, after admixture with these juices, the form of an emulsion. In this way the fat is rendered absorbable by being enabled to pass through the fine pores of the mucous membranes, ulti- mately reaching the blood system. While treating of this subject it is convenient to draw attention to the power of ordinary phosphate of sodium to emulsify certain fatty acids, and it is to the presence of this substance in bile that Thudichum (see his ' Chemical Physiology ') attributes its property of emulsification. , In the duodenum the bile also causes a precipitation of peptones, and these being passed down the intestines with biliary acids and colouring matters, are altered and absorbed by the digestive influence of intestinal juice. It is supposed that in the intestines the biliary acids split up, yielding taurine and glycocin, which return into the circulation, but the cholic acid (their complementary product) disappears for the most part. It is true a cer- tain part of it occurs in the fseces, but this by no means accounts for the whole quantity, and it is not improbable that a large proportion of it is likewise absorbed into the system. The pancreatic and' intestinal juices also complete the transformation of the starchy matters present in chyme into glucose, and so, in one way or the other, the food introduced into the alimentary canal is rendered soluble and absorbable so far as this is possible. The destiny of the bihary colouring matters is un- known, beyond the observation which has been made, that they are profoundly changed. By means of the peristaltic contractions, the chyle is thrust alono; the small intestine, and the vessels of the 7S ORGANS, FLUIDS, ETC., CONXERNED IN DIGESTION. villi absorb the dissolved matter, and admit of the pas- sage of the mimitely divided particles of fatty matter. At the same time much of the chyle enters the lacteals, and only reaches the blood system after travelling along the mesenteric lymphatics and the thoracic duct. Passing through the ileo-ca3cal valve, the digested matters enter the ccecum and the large intestine, and by this tmie they constitute a more consistent mass, owing to the removal of soluble and liquid matters. What remains is the insoluble residue of the food, and changed principles which have been of influence in its digestion. It is in the large intestine that the excrementitious matters assume an acid reaction and peculiar odour, both of which features become more marked as they approach the rectum. It has been supposed that the acid reaction alluded to is owing to processes of fermentation arising in starchy matter which has escaped conversion into glucose, but the grounds on Avhich this statement rests are far from satisfactory. THE FAECES. General Description of Fceces. — Faeces represents the undigested and altered portions of the food which have refused absorption ; its quantity and composition there- fore necessarily vary with the nature and amount of the food. It contains certain changed products derived from biliary matters and the juices involved in digestion. The faeces often have an acid reaction, which has been ascribed to the presence of lactic and butyric acids, though more often they are quite neutral and sometimes alkaline ; as for the colour, this depends largely upon the COMPOSITION OF F^CES. 79 nature of the diet, a flesh diet imparting a dark colour, while much milk causes them to be yellow. This last fact is probably connected with the observation of Thudichum, that the fseces of children at the breast contain a yellow matter, soluble in alcohol, and exhibit- ing an absorption band in its spectrum at the beginning of blue. Thudichum names this unknown substance ' intestino-luteine.' The fgeces are more solid, and of a paler colour, when a bread diet is more resorted to. Many chemical reagents taken as medicines have an influence upon the colour of the fasces ; thus it is well known that iron preparations give a black colour to the f^ces, while mercurial ones lend a green colour. Composition of Fceces. — Beyond the normal consti- tuents of feeces, many extraordinary ones are hable to be found present, and depend also upon the nature of the food,.&c. In illustration of this it may be stated that, in conjunction with Paul, the author has recently shown,^ that when the diet includes preserved peas containing copper, this substance is excreted for the most part in the fgeces. The copper exists in the form of an insoluble combination with the substance of the peas (albumin), and to a great extent resists digestion. E, Yogt^ found weighable quantities of morphine in the fseces of a man who had taken large quantities over a period of some years. Unchanged bile is never met with in fseces, and Schmidt has shown that one half of the bile efiiised into the intestinal canal is decomposed before it reaches the middle of even the small intestine. Several products, ^ Pharm. Journ. September 1877. 2 ^,.c^_ Pharm. (3), vii 23, 26. 80 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. liowever, derived from bile are to be found in the fseces, as will be hereafter shown. Meconium, or the matter found in the intestinal canal at birth, consists for the most part of biliary matters. Here it should be stated that Pettenkofer's test for bile is by no means reliable, and the explanation of this is given in a special chapter. At times certain matters are recognised to be present in fasces which admit of digestion and assimilation ; therefore, when these occur they must be regarded not as excrementitious matters in the proper sense of the term, but as materials which have escaped, from some extraordinary circumstances, the action of the stomachic and the various digestive influences. Such a state of things often indicates conditions of disease. As regards the odour of faeces, it in no way indicates any process of a putrefactive kind, but is merely a pro- perty of certain matters which are present, and which may otherwise be produced, as, for instance, by the action of alkalies (when fused) upon such bodies as casein, gelatin, and fibrin (Liebig). When out of the body, however, Liebig has shown that fseces are liable to putrefactive change, and have then the power to com- municate a state of fermentation to other substances, such as sugar solutions. The amount of water present in fasces is not a fixed quantity, but averages about 73 to 75 per cent.; it also contains about 26 per cent, matter, dry at 100°C., but this is the average of quantities ranging from 17 to 31 per cent. Faeces contains but little nitrogen ; Dr. Edward Smith has stated that on the average the daily elimination of nitrogen by the bowels amounts to about 3 grms. Liebig calculates that a healthy adult excretes about COMPOSITION' OF FiECES. 81 5^ ounces of feces in twenty-four hours, but it is a vary- ing quantity, and as often amounts to 7 or 8 ounces. Mucus is present to the extent of a few per cents., and it is by no means improbable that the habihty of f^ces to putrefaction exhibited after removal from the body resides in this substance, which is known to be remarkably prone to such decomposition. Fseces generally contains but small quantities of salts, consisting of phosphates of calcium, magnesium, sodium, and potassium ; traces of iron are also present, and some- times crystals of the ammonia-phosphate of magnesium. Chlorine and sulphuric acid occur only in traces. Small quantities of albumin in a soluble form, and fats are also often met with, as well as glucose. This last-named substance is supposed to result from the action of pancreatic juice upon starchy matter in the intestine. Among the altered biliary matters excreted in the fseces there occur dyslysin, cholalic acid, choloidinic acid, taurin, and other perfectly undefinable substances chiefly derived from the biliary colouring matters. The undi- gested matters present in fseces include fat of a waxy and partly unknown nature, starch granules, cellular and muscular fibres, cellulose, particles of bone, &c., &c. Gases are often occluded in the intestine, and more especially in cases of imperfect digestion ; they consist for the most part of carbonic anhydride, with variable quantities of marsh gas (CH^) and hydrosulphuric acid (HgS). These symptoms are often painfully increased in disease ; thus, in typhus fever, the stomach is often found distended with gas. Some years ago Marcet submitted fseces to an elabo- rate investigation which was attended by a number of in- 82 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. teresting results, the chief of which was the discovery of a nev/ organic substance of an alkahne reaction, and which he named excretin. It is very soluble in ether, but sparingly soluble in cold alcohol ; insoluble in water and crystallising in acicular forms. It fuses between 95° and 96° C, and burns away at higher temperatures leaving no ash. Ultimately, Marcet gave to this sub- stance the formula C^sHiggSOg. More recently F. Hinter- berger^ has re-investigated the matter, and found that Marcet's excretin was a mixture, the pure substance being free from sulphur and consisting of CaoHagO. It is obtained by exhausting fresh faeces with boiling alcohol, and allowing the extracts to stand over a week, filtering from the black precipitate which forms, and precipitation with milk of Ume. The precipitate thus obtained, after drying, yields the pure excretion to a hot mixture of ether and alcohol, and on cooling the extract below 0°, it deposits in the form of yellow needles. A hundred pounds of faeces yielded 8 grams of the pure material, which forms, with bromine, a crystalUne substitution pro- duct of the formula CgoHoiBrgO. Marcet also examined the deposit thrown down on standinjT from the alcoholic extract of fresh fseces, and describes it as a soft fatty body which he named ex- cretolic acid. This fuses between 25° and 26° C, and is not saponifiable by boiling potash. It is soluble in ether, but insoluble in water. It has never been analysed. Stercorin is the name given by Dr. Flint to a sub- stance which he found in faeces, and which he considers to be derived from cholesterine. It has not been ana- 1 Ann. Chem. Pharm., clxvi. 213-216. F^CES IN DISEASE. 83 lysed, but from its described characters it appears to be related in some way to, and is perhaps identical with, excretin or excretolic acid. Playfair found, in a sample of faeces which he ex- amined, as much as 15 per cent, of nitrogen and 45 per cent, carbon, and from the amount of nitrogen and phos- phates present, human fseces has often been recommended as a useful manure. Various plans for dealing with it have been from time to time discussed at the Society of Arts in London and elsewhere. Quite recently, H. Schwarz has proposed^ a process which consists in heat- ing human excrements with milk of lime, condensing the ammonia which is evolved, and separating and pressing the lime mud which is obtained ; it is this mud which is recommended as a manure, but it appears to be of small value. Fceces in Disease. — In the mucous evacuations from a case of intestinal catarrh, Liebig detected the presence of alloxan, an oxidation product of uric acid. Under abnormal conditions, uric acid, urea, leucine, &c., have also been observed present. These are facts which possess some sort of connection with the great process of oxidation which is constantly going on in the body, but the nature of the relation is quite unknown. In cholera and typhus it has been stated that the serous evacuations contain much soluble albumin. Thu- dichum has examined cholera evacuations, and has incor- porated the results in a report '^ on cholera. ^ Dingl. polyt. J., ccxx. 161-171. ^ Hepoi'ts of the Medical Officer of the Pi-ivy Council, Sj-c. q2 84 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION, CHAPTER VII. CHEMISTRY OF THE BILE. It is not intended in this place to discuss the function of the liver; that will come hereafter. Here it will suffice to state that beyond all doubt, the great purpose served by the liver is the production of bile, which it elaborates by unknown processes out of the matters contained in the blood which feeds it. The general characters of bile have been already described ; it is now necessary to study the chemistry, so far as it is known, of those constituents of bile with which we are acquainted. These may be said to be glycocholic and taurocholic acids (which exist as sodium salts), cholesterine, and the various biliary pigments. Glycocholic acid, C26H43NO6. — This acid constitutes the greater part of the resin of ox bile, but it is only present in small quantity in human bile. It is best obtained by fully extracting dry bile with absolute alcohol, and frac- tional precipitation of the extract with ether. The first precipitates consist for the most part of colouring mat- ters ; the latter ones are crystalline, and contain the sodium salts of glycocholic and taurocholic acids. The mixture last named is dissolved in water and precipi- tated by acetate of lead, when taurocholate of lead re- mains for the most part in solution. On decomposition of the lead glycocholate dissolved in hot alcohol, with GLYCOCHOLIC ACID. 85 sulphuretted hydrogen, the free acid is obtained, and is deposited as a white crystalline mass from the filtrate after removal of the sulphide of lead. It is obtained in a purer state if the bile be first decolorised by animal charcoal, and it then only requires washing with water to be quite pure. Gorup Besanez recommends the extraction of dry bile with alcohol of 90 per cent. ; distillation of the excess of alcohol ; dilution of the residual extract with water, and precipitation with milk of lime. In this way most of the colouring matter is thrown down in combination with the lime, and on neutralisation to faint acidity with sul- phuric acid, the filtrate gradually deposits crystals of glycocholic acid. Glycocholic acid forms long silky needles, which lose weight at 100° C; it is sparingly soluble in cold water, but dissolves freely in hot water. Eecrystallisation from water may therefore be resorted to as method of purifi- cation. It is sparingly soluble in ether. The salts which it forms with the metals of the alkalies and earths are crystalline, and are soluble in alcohol. Its aqueous solution is not precipitated by neutral lead acetate, mercuric chloride, or nitrate of silver, but the lead, copper, iron, and silver salts may be obtained by precipitation from its sodium salt held in solution. The sodium salt will not crystallise from water or al- cohol, but dries up to a varnish ; it exists in this form naturally in bile. The soluble glycocholates are decomposed by acetic and other acids, with the precipitation of glycocholic acid in a viscid form. SQ ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. When glycocholic acid is boiled with a solution of baryta water, it is decomposed as follows : — C,eH,3N0e + BaH,0, = Ba(0, JI3P5), + 2C,n,N0,. That is to say, the barium salt of cholic acid, and glyco- cine are produced. Acids decompose it in a somewhat different manner; a molecule of water is first removed, and cholonic acid, C26H41NO5, is produced ; this tlien decomposes into cho- loidic acid, C48H78O9, and glycocine ; finally the choloidic acid is resolved into dyslysin, C48H72O6. It is not at all unlikely that the dyslysin and other allied compounds, the presence of which has been re- marked in the faeces, results from a similar decomposition instituted by the acid of the gastric juice under condi- tions governing intestinal digestion. In that case glyco- cine would probably be reabsorbed into the system, and this view derives considerable support from some facts now to be mentioned. Hippuric acid, C9H9NO3, is not a normal constituent of human urine, but is found in that of the horse and cow. But when benzoic acid is being taken, hippuric acid is found in the human secretion, and, curiously enough, hippuric acid readily decomposes by the agency of acids, as follows : — O9H9NO3 + H5O = O^HgO, + C^ll^xo.,. That is to say, it spHts up into benzoic acid and glyco- cine, suggesting the probability that the hippuric acid, when found in man's urine, has resulted from a S3mthesis of these substances by the removal of one molecule of water. It will be seen in another place that glycocine TAUEOCHOLIC ACID. 87 also bears a decided relation to many other bodies found in urine. Taurocholic Acid, C26H4gNS07. — This constituent of bile, which is peculiarly characterised by the sulphur it contains, is less abundant in ox bile than the correspond- ing acid. In the human bile, however, the order of things is reversed, and taurocholic acid is the most abundant (in dogs it is the only one). It is prepared from the mother liquor resulting after the precipitation of the glycocholate of lead. As tauro- cholic acid is only precipitated by basic lead acetate, ammonia and more acetate of lead must be added to the mother liquor referred to. The precipitate is purified by dissolving in alcohol and reprecipitating by water, after which the alcoholic solution is decomposed with sulphuretted hydrogen, the sulphide of lead is removed, and the solution concentrated. The free acid may be obtained on evaporation, or by precipitation with ether, when it is deposited as a syrup which crystallises on continued standing. Heintz recommends the direct precipitation of bile with normal lead acetate, and the precipitation of the filtrate with basic lead acetate, until the precipitates are white and of a plaster-like consistence. The ultimate filtrate yields nearly pure taurocholate of lead, if now precipitated with a mixture of basic lead acetate and ammonia. The combinations of taurocholic acid with the alkali metals are very soluble in water and alcohol ; the basic lead salt is soluble only in boiling water. When decomposed by boiling with acids, it splits up much in the same way as glycocholic acid, yielding 88 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. cholic or choloidic acids, or dyslysiii ; glycocine (glyco- coll), however, it does not yield, but in its place taurin appears — CjeH^jNSO^ + up = CjH^NSOj + C^^H^oOs. Baryta water, when boiled with taurocholic acid, also decomposes it, giving cholate of barium and taurin. This same decomposition would ap]:)ear to take place in the small intestine, taurin being found in the intesti- nal canal to some extent ; most of it, however, gets into the circulation, and the sulphur it contains, representing the whole of that contained in bile, is excreted in the urine as sulphuric acid. Cholic Acid (C20H40O.5). — This acid may be obtained as already described under taurocholic and glycocholic acids. Although it is probably produced as a decom- position product in the body, it is nowhere met with, and hence it would api)ear to become burnt up in the circu- lation. It crystallises from alcohol in colourless glassy forms, but as obtained from its barium salt by decomposition with hydrochloric acid, it forms a resinous mass. Cholic acid is slightly soluble in water, more so in ether, and still more in hot alcohol. Its ethereal solution deposits the acid in rhombic tabular crystals, which contain one molecule of water of crystallisation wliich may be ex- pelled at a gentle heat. At a higher temperature it loses water of constitution, and successively becomes choloidic acid and dyslysiu. The potassium, sodium, and barium chelates are soluble in water and in alcohol, and from the latter CHOLIC ACID. 89 menstruum most of tlie salts crystallise, although in many characters they approach to the nature of soaps. On oxidation with nitric acid, cholic acid yields cholesteric acid (CgHioOg). Cholic acid fuses at 195° C„ and crystallises with 2J molecules of water, if we accept the C20 formula, but in all probabihty this formula will have to be multi- plied. F. Baumstark,^ by acting on an alcoholic solution of cholic acid wdth hydrochloric acid, has obtained an ether of the formula 0241139(02115)05, which splits up by caustic alkalies into cholic acid and ordinary alcohol, but when heated with alcoholic ammonia to 120° it is said to yield cholamide, O24H39O4H2N, which is identical with the amide obtained on heating ammonium cbolate. The same chemist has also obtained ethyl-benzoyl-cholate, 024H38(02H5)( 071150)05 by the action of ethyl-cholate upon benzoyl chloride. H. Tappeiner^ states that when cholic acid is oxidised by chromic acid (potassic chromate and sul- phuric acid), it yields acetic acid and a fatty acid which is either palmitic or stearic, and a second acid wdiich is crystallisable and melts at 250°. These facts remind forcibly of the relation of chohc acid to oleic acid, which splits up also into acetic and palmitic acids by the action of fused alkalies. In an attempt to ascertain the nucleus of cholic acid by distillation with alkali, F. Baumstark obtained a semi- fluid oil, the nature of which, however, was not ascer- tained.^ . 1 Deut. Chem. Ges. Ber., vi. 1185, 1187. 2 Deut. Oiem. Ges. Ber., vi. 1285. 3 Deut. Chem. Ges. Ber., vi. 1377, 1379. 90 OKGAXS, FLUIDS, ETC., CO^X'ERNED IN DIGESTION. When cholic acid is subjected to dry distillation it yields a volatile product said to exhibit the properties of phenol ; and when distilled with alkalies, it yields volatile products between 150° and 280°, which give the Pettenkofer reaction. Gorup Besanez states^ that by melting the acid with potassic hydrate, acetic and propionic acids are formed, and a substance resembling dyslysin. From these and other considerations, which will be insisted upon more particularly when treating of the Pettenkofer reaction, there is little doubt that between certain bile compounds and the fatty acids on the one hand, and certain benzene derivatives on the other hand, there exists some close relationship. By acting on cholic acid with phosphorous chloride, a phosphorised product has been obtained according to some such reaction as is here given — 30,,H,,o, + 2POI3 = 0,,H„,P,0,, + 6HCI. This phosphorised product has been compared to certain compounds also containing phosphorus, which exist in brain and nerve matters. As we come to study the chemical constitution of the brain, it will be seen that this comparison is to some extent justifiable. But there is this difference presented by all the phosphorised principles present in brain matter, that they are also nitrogenous. Attempts to produce amidated compounds from the above-mentioned artificial phosphorised com- bination would no doubt yield singularly nnportant and valuable results. Between the chemistry of the brain and bile compounds there is much in common. 1 Ann. Ch. Pharm. clvii. 282. CHOLOIDIC ACID : GENEEALISATION". 91 Choloidic Acid (C48H78O9). — This acid, so-named by Demarcay, is derived, as already explained, from two molecules of cholic acid by the removal of one of water. It is a resinous white, friable substance, freely soluble in alcohol, but shghtly so in ether, and altogether insoluble in water. The salts of the alkalies are soluble in water and alcohol, but do not crystallise. The barium salt is insoluble in water. Eedtenbacher .has determined that when the acid is distilled with nitric acid it yields volatile fatty acids of the series CnHsnOa, including acetic, butyric, caproic, oenanthylic, capryhc, pelargonic, and capric acids ; oxalic and cholesteric acids remain behind, and a third crystal- lisable acid termed choloidanic (C16H24O7). In the transformation of choloidic acid into dyslysin under the influence of acids, each molecule loses three of water and becomes C48H72O6, which is a body fusible at 140° C, and behaves like a resin. Generalisation. — Among many of the substances described in the preceding sections there are several rela- tions perceptible which are of great importance, both physiologically and chemically. Thus it has been shown that cholic, choloidic acid, and dyslysin each give, as an oxidation product, cholesteric acid. Choloidic acid yields also other products like to those given in a similar process by oleic acid. Moreover, all of these acids, and the conjugated glycocholic and taurocholic acids, as well as cholesterine, yield with sugar and sulphuric acid a re- action which Pettenkofer, at the time of his discovery, considered characteristic of bile compounds. Choles- terine (C26II44O) also yields cholesteric acid as an oxida- tion product. Now, in a subsequent chapter on the 92 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. Pettenkofer reaction, the relation of these bihary acids to oleic acid and the members of the ftitty acid series generally ^vill be still more fully developed ; in the meantime, that there is a connection between the bile acids and cholesterine on the one hand, and the whole of these to oleic acid on the other hand, seems evident. Again, the bile of the pig contains a resinoid acid termed hyocholic, of the formula C27H43NO6, and this splits up in a manner similar to glycocholic acid, yielding glycocine and hyocholahc acid, thus : — 0„H,3N0, + 11,0 = C,II,NO, + C,,H,A- Hyocholaho acid may furtlier split up into water and hyodyslysin, CsoHjgOe, a body which is homologous with ordinary dyslysin. Further, the sulphuretted acid of pig's bile, which is complementary to hyocholic acid, has the formula C27H45NSO6, and is related to taurocholic acid as hyocholic is to glycochohc acid. Glycocine or Glycocoll (C2H5NO2). — As stated while describing glycocholic acid, glycocine is produced by the decomposition of this substance into its proximate nuclei. It is also yielded as stated above by a similar decomposi- tion of hippuric acid. Most interesting is the derivation of glycocine from gelatin when boiled with dilute sulphuric acid, or with potash or soda — interesting, because, as will be shown hereafter, it is from albuminoids similar to gelatin that the liver elaborates the bile, one of whose constituents is glycochohc acid which yields glycocine. By evaporation of its aqueous solution the base may be obtained in hard, sweetish crystals. The artificial synthesis of glycocine has been effected by several methods. Thus, Perkin and GLYCOCINE AND ITS SYNTHESIS. 93 Diippa ^ obtained it by acting upon an alcoholic solution of ammonia with broraacetic acid at an elevated tempera- ture, the following reaction taking place : — O^HaBrOs + 2NH3 = O^HgO^NHa + NH^Br. That is to say, amido- acetic acid (glycocine) and am- monium bromide are produced. A. Emmerling ^ performed the synthesis by passing a current of cyanogen through a saturated boiling solution of hydriodic acid, thus : 2(0N) + 5HI 4 2H,0 = O^H^NO^ + NH J + 1,. Strecker found that by acting on uric acid with hydriodic acid, glycocine was also produced, and this fact led him to beheve that uric acid contained a glyco- cine residue ; Emmerhng, however, says the fact is due to the presence of a cyanogen molecule in uric acid. Glycocine is soluble in about 400 parts of cold water, but insoluble in alcohol or ether. It forms combinations with variable molecular proportions of hydrochloric, nitric, sulphuric, and oxalic acids ; and many of these, such, for example, as the nitrate CsHgNOgjHJSTOg, crys- tallise. It also behaves as an acid towards bases, forming many soluble compounds with metallic oxides which are also crystalline. Compounds of zinc, copper, lead, barium, calcium, and silver are known. It reduces merciu-ous nitrate and expels acetic acid from acetate of copper. Heated with strong potash solution, a transitory fiery-red colour is produced, ammonia is set free, and oxalic and hydrocyanic acids 1 Q. J. Chem. Soc, xi. 31. 2 2)eMiJ. Chem. Ges. £er., vi. 1351-1354. 94 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. are formed in the solution. Beyond behaving as an acid and as a base, it behaves also, in some respects, like an alkaloid, forming combinations with salts which are crystalline. A mixture of sulphuric acid and manganic dioxide gives, on distillation with glycocine, carbonic anhydride and hydrocyanic acid, thus — C2H5NO, + O, = CO., + 2H,0 + HON. By the passage of nitrous acid through its aqueous solution, glycocine is resolved into nitrogen and glycolic acid, as follows — O2H5NO2 + HNO, = C2HP3 + H„0 + N,. The glycolic acid may be extracted by ether. According to E. Dreschsel,^ an ammoniacal solution of glycocine, when treated with a solution of ammonium permanga- nate, yields carbonic, carbamic and oxamic acids ; dioxide of manganese being precipitated. He also states that the same products are given by similarly treating leucine, tyrosin, or albumin, and he concludes that carbamic acid is always formed when carbon dioxide and ammonia act upon each other in the nascent state. From his experiments (which are not, however, of absolute pre- cision) he infers that, in the formation of urea from albuminoids, glycocine, leucine, and tyrosin are first formed, and that these are subsequently oxidised into a carbamate, out of w^hich some ferment arranges urea. This must be regarded, however, as highly problematical, notwithstanding that Schiitzenberger has recently ob- 1 Journ.pr. CJiem. (2), xii. 417-426. GLYCOCINE : ITS EEACTIONS. TAUEIN. 95 tained decisive evidence of the production of urea from albumin. Of this more anon. E. Engel states/ the coloiur-reaction said to be yielded by glycocine and alkalies is due, when observed, to impurities, and that the reactions with mercurous nitrate and copper sulphate are not sufficient to characterise it. He gives two new reactions, which are as follows. With ferric chloride, glycocine gives an intense red colour, which disappears on the addition of acids, and is reproduced by ammonia. A drop of phenol and some sodium hypochlorite gives, with a solution of glycocine, a fine blue coloration ; other amines, however, behave similarly. Before concluding, it may be noticed that K. Kraut,^ in a study of glycocine derivatives, states that when silver glycocine acts upon methyl iodide, the methiodide of methylic dimethylamidacetate is formed, from which oxyneurine can be produced. This fact is interesting by bringing into plausible relationship bodies which occur in the animal organism, and which must have a common origin — namely in albuminoids. Taurin (C2H7NSO3). — This substance, which can be detected in the faeces, is obtained from taurocholic acid as described under that substance. Cloetta has detected it in small quantity in the lungs of the ox, and has estab- lished its identity with the substance named by Verdeil pneumic or pulmonic acid. It is isomeric with sulphite of aldehyd-ammonium (C2H40,NH3,S02), from which, however, it differs in its properties. Taurin appears to be dehydrated issethionate ^ Bull. Soc. Chim. (2), xxiii. 435-437 ; and Compt. Rend. Ixxx. 1168. 2 Liebig's Annalen, clxxxii. 172. 96 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. of ammonium, and was prepared synthetically by Strecker ^ as follows : — Isetliionic acid (prepared from olefiant gas and sulphuric anhydride) in aqueous solution is neu- tralised with ammonia, and the solution on evaporation yields crystals of the salt NH4C.2H5SO4, which, on heating to 230° C, loses water and yields taurin, thus — NH^O.HjSO^ = 11,0 + 0,II,NS03. E. Engol, however, points out^ that the body thus obtained differs from taurin proper in its fusion point and by the fact that it yields ammonia when boiled with potassic hydrate. From further researches, he concludes that taurin is not isethionamide, but a glycocine or acid amide which may be synthetically prepared by acting on ammonia wnth chlorethylsulphurous acid. Engel shows its further similarity to glycocine by having prepared a basic salt of the formula CgHeHgNSOa + HgO. Taurin crystallises in forms like quartz ; it is soluble in 16 parts of cold water, but is insoluble in absolute alcohol (although it dissolves in weak alcohol) and in ether. On burning in the air, it yields sulphurous anhydride. Potash dissolves it, and on evaporation am- monia is evolved, while potassic sulphite and acetate are formed. It is oxidised in the system, and the sulphur is excreted in the urine as sulphuric acid. Cholesterine (C26H44O). — This beautiful substance, entering into the composition of bile, occurs still more largely in brain and nerve substance ; it is also met with 1 CJiem, Gaz., 1854, 388 ; and Verh. d. phys.-med. Ges. zu Wiirzhurg, Bd. 2, S. 299. » Compt. Rend., Ixxx. 1398-1400. CHOLESTERINE. 97 in the yelk of egg, the seminal fluid, and in blood attached to the corpuscles. It has been found in milk, the spleen, the excrements of various animals, in the corpus luteum of the cow, in peas, and other vegetable substances, &c. In several morbid products, as gall-stones, the fluid of hydatid ovarian cysts, and pus, cholesterine also occurs, while it is a common product of putrefactive changes in muscular tissue. The quantity present in bile is variable, and is, according to Berzelius, one in 10,000, while, according to others, bile contains as much as 0*25 per cent. From its ready solubility in, and crystallisability from alcohol or ether, it is easily obtained in a pure state ; if required to obtain it free from fatty matters, this is best done by a process of saponification, by which the choles- terine is not attacked, and consequently may be readily extracted from the soap by ether. Cholesterine is practically insoluble in water, and crystallises in beautiful pearly plates somewhat resembling naphthahne. These crystals may be obtained in a form containing 5 per cent, water of crystallisation which is expelled at 100° C. It fuses at 137° C, and at a higher temperature may be distilled unchanged, if care be taken ; but at still higher temperatures it decomposes. By heating cholesterine during some hours in sealed tubes with various acids, certain compounds termed cholesterides are obtained (Berthelot), resembling saccha- rides in their general nature. These may be regarded as the ethers of cholesterine (itself a monobasic alcohol, C26H43HO, according to Gerhardt). Thus the following compounds have been obtained — butyrocholesterine, C26H43,C4H702 ', stearocholcstenne, C26H43,Ci8H3502 ; and H 08 OKGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. benzocholesterine, C26H43,C7H502 They are white fusible bodies, and but sparingly soluble in hot alcohol, but dissolving easily in ether. By the action of alcoholic solution of potash, they decompose, yielding cholesterine and the various acids from which they are relatively con- structed. Sodium cholesterate, CssH^jNaO, is produced by the action of metallic sodium upon cholesterine dis- solved in petroleum spirit. This body, when heated with ethyl iodide, gives cholesteryl oxide. Cholesteric acetate, C26H43(C2H30)0, is prepared by the action of acetyl chloride on sodium cholesterate or cholesterine. Cholesteryl chloride, C26H43CI, may be obtained by acting upon cholesterine with phosphorous pentachloride ; when decomposed with aqueous potash it yields choles- terine and potassic chloride. Cholesterylamine, C2CH43NH2, results when the body C26H43CI is digested with alcoholic ammonia ; it is crystal- line, and melts at 104° (Henry). The action of terchloride of phosphorus upon choles- terine yields neutral phosphorised bodies difficult of puri- fication, and resembling, according to Gorup Besanez,^ the so-called myelin ; this, however, is only partially true, as myelin is also nitrogenous in character. Strong sul- phuric acid removes water from cholesterine, and gives rise to the production of three hydrocarbons of the formula C26H42 named cholesterilin. Nitric acid oxidises cholesterine, and yields (like the biliary acids) cholesteric acid, CgHjoOg, which is a yellow, deliquescent substance readily soluble in alcohol ; other ' A7m. (7i. Pharm. clvii. 284, OXIDATION-PRODUCTS OF CHOLESTEEINE. 99 acids of tlie series CnHjnOs, and oxalic acid, accompany the cliolesteric acid. By oxidation of a milder character, such as is pre- sented by a mixture of sulphuric acid and potassic dichromate, a white amorphous acid, termed oxycholic, C23H40O6, is produced, and certain members of the fatty acid series. LatschinoJBf has studied^ the oxidising action of potassium permanganate upon cholesterine, and has obtained three different acids whose salts he has separated by the use of different solvents ; the acids are — cholesteric acid, C26H42O4 ; oxycholesteric acid, CsgH^sOs ; and dioxy- cholesteric acid, C26H42O6. By the action of bromine upon cholesterine dissolved in carbon disulphide, an additive product of the compo- sition C26H440Br2 is obtained. It crystallises in white needles, and is insoluble in water, but dissolves readily in ether. Sodium amalgam reconverts it into cholesterine. Cholesterine rotates a ray of polarised light to the left. When evaporated with a drop, of nitric acid at a gentle heat it leaves a yellow spot, which turns red when moistened with ammonia.. By heating with a mixture of 2 or 3 volumes of strong hydrochloric or sulphuric acid and 1 volume of moderately dilute ferric chloride solution, and evaporation to dryness, a reddish violet residue is obtained. In strong sulphuric acid, cholesterine dissolves to a reddish colour, and on the addition of sugar (concentrated solution) the Pettenkofer reaction is exhibited. E. Schulze has shown ^ that sweat contains, besides "• Budl. Soc. Chim., xxvii. 456. ^ Journ. Chem. Soc, vol. xi. (ser. 2), p. 513,; and J.pr. Chem. (2), vii. 163-178. H 2 100 OKGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. cholesterine, a modification of the same principle termed Ijy him isocholesterine. It is particularly distinguished by depositing from its alcoholic solution as a translucent jelly ; this was when it had been obtained from its ben- zoate by the action of potash, Tlie author of this treatise has often observed, however, cholesterine from normal sources to beliave similarly when recrystallised from benzene, and hence it appears doubtful whether more than one cholesterine really exists ; a surmise which is supported by the identity of reactions and properties pre- sented by cholesterine and so-called isocholesterine. BILE PIGMENTS. Bilirubin (C9H9NO2). — Of the biliary pigments, that M-hich has been best studied is bilirubin, also called cholophoeine. It is readily prepared by extracting in- spissated bile, or, what is better, crushed gall-stones,^ successively with water, alcohol, dilute hydrochloric acid, boiling alcohol, and ether ; the residue is dried and then extracted with boiling chloroform, which assumes a yellow colour as the bilirubin dissolves. The chloroform extracts when saturated, deposit minute crystals of bili- rubin on cooling, but it is best to concentrate the solution by distillation, and to precipitate the fioal extract with alcohol. ' Maly (Annalen der Chemie, clxxv. 70, 77) has given the following analysis of ox gall-stones : — Soluble portion . = 18-09 Ethereal extract (fat) . . = 5-28 Phosphates and bases . . = 1-41 Bilirubin .... . = 28-10 Residue and loss . . = 47-12 BILmUBlK 101 The reasons for using the above method are as fol- lows : — The water extracts whatever is soluble therein, such as mucus, salts, &c. ; the alcohol takes out cholester- ine, fatty and biliary acids ; the acid decomposes the lime salt of bilirubin (for it exists in combination in gall- stones), and removes the lime ; the alcohol and ether finally complete the extraction of soluble matters pro- duced by the previous use of the acid, and dissolves only traces of bilirubin, which is, however, easily soluble in chloroform. It is also soluble in bisulphide of carbon, turpentine, and benzene. In the form of powder, bilirubin is of a brilhant red colour; its crystals have a bluish shade over the red. The bihary calculi of oxen derive their yellow colour from the presence of bilirubin, and are much valued by artists for compounding pigments of a brilliant tint and durable character. Stadeler assigned to bilirubin the formula CigHigNaOs, but he afterwards withdrew this formula, and taking more extensive results obtained by Thudichum,^ constructed upon them the theory of bilirubin as a hexabasic acid. Thudichum, however, has protested^ against this, and indeed his work is entirely opposed to the conclusions drawn by Stadeler. Maly^ has also occupied himself with studies upon bilirubin; but as his results, so far as they have been estabhshed, are merely confirmative of those obtained ' lOtk Report Med. Officer of Privy Council, 1867, pp. 240-251 ; also Journ. f. pract, Chemie, 104 (1868) 4. ^ Journ. Chem. Soc, May 1875, * Maly's researches are summarised and criticised loj Thudiclium in an open letter to the Vienna Academy. See Chemical News of April 13 and 21, 1876. 102 ORGANS, FLUIDS, ETC., COXCEKXED IN DIGESTION. previously by Thiidichiim, we shall confine ourselves to the researches of the latter. He has shown that from a solution of bihrubin in very dilute ammonia, nitrate of silver precipitates the compound C;,H8AgN02,H20. Chlo- rides of barium and calcium, precipitate from a similar solution, compounds of a red colour and of the composi- tion 2(C9H8NO.,)Ba,C9H9N02 + 2HoO and 2(C3H8N02)Ca, C;)H9N02,2H20. Beyond these, the same chemist has also described the follow^iug preparations : — Basic silver salt Cgll^AgoNOj Neutral barium salt . . . 2(C9H8N02)Ba^2H,0 „ calcium salt . . 2(C9ll8NO,)Ca,2H.,0 Acid zinc salt . . 2(C9H8XO,)Zn,C9ll9NO,,2H",0 Basic lead salt CgH^PbNO.^ If bilirubin be dissolved in caustic or carbonated alkali, and the solution exposed to the air for some days, the product turns green, and on addition of hydrochloric acid, green flakes of biliverdin (CgHgNOa) are produced, and may be purified by regeneration from an alcoholic solution. By the action of nitric acid containing nitrous acid, upon bilirubin, a play of colours is produced, passing from green, blue, violet, and red to yellow. Briicke modified this test, and recommends the use of boiled pure nitric acid and the cautious addition of sulphuric acid to the bottom of the test-tube. E. Fleischl^ has simplified the test by using a concentrated solution of sodium nitrate instead of the freshly boiled nitric acid. If concentrated nitric acid be added to an ammo- nia cal solution of bilirubin, a blue precipitate is formed at a certain stage. This is soluble in alcohol, and has * Chem. Centr, 1875, p. 5G8, BEOMKs^ATION OF BILIRUBIN. 103 been termed cholocyanin ; it presents a characteristic spectrum. Concentrated sulphuric acid gives with bili- rubin a green solution, and this in contact with a moist atmosphere, or on the addition of water, gives, among other products, cholothalline, C9H11NO3. There is no established connection whatever between bilirubin or other biliary pigments and the colouring- matter of blood ; it is necessary to state this emphatically on account of the existence of erroneous statements and impressions to the contrary. Thus, Maly ^ obtained by heating bilirubin suspended in water with sodium amal- gam in excess, a body which he termed hydrobilirubin, and which he viewed as identical with the colouring- matter of urine ; but Thudichum ^ has demonstrated the inaccuracy of the latter proposition. When dry bilirubin is exposed to the dry vapour of bromine, it forms the substitution product C9H7Br2N02 : this is stable at 100° C, and constitutes a dark blue- black powder soluble in dilute acids to a blue colour, Thudichum has also described the following compounds : CgHgBrNO, and C9H8BrNO,C9HoN02. This chemist had by earlier experiment fixed the atomic weight of bili- rubin at 163, a figure which is confirmed by the direct bromination experiment leading to the production of CgHyBraNOs : the only doubt about this formula which now remains, attaches to the hydrogen ; this figure may possibly have to be increased.^ Iodine vapour has no action upon bilirubin, but chlorine gas seems to give several substitution products, among them C9HgCl4N02. ^ Ann. Chem. Pharm. 1872, No. 7, p. 77. * Journ. Chem. Soe., May 1875. ^ See analyses executed by tlie author for Tiudichum, ani described on p. 9- of Thudichum's open letter. 104 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. Bilirubin is the substance which is supposed to give ihe colour to the skin in ' yellow jaundice,' while ' black jaundice ' colour is due to the retention of biliverdin ; these principles may be extracted from the skin in jaun- dice (bilirubin by chloroform, and biliverdin by alcohol^). As before stated, the further history of the biliary pigments after they mingle with the contents of the in- testinal canal is practically unknown, Biliverdin (CgHgNOj). — As already explained under bilirubin, this substance is best produced by Heintz's process, wliich consists in passing a current of air through an alkaline solution of bilirubin and precipitation of the resulting solution by means of hydrochloric acid. Biliverdin is soluble in alcohol, benzene, and carbon disulphide, but insoluble in water, ether, and chloroform. In a fiu'ther investigation of the properties of bili- verdin, Thudichum^ has confirmed his hypothesis ac- cording to which it is produced from bilirubin by the reaction C9H9N02 + 02=C02 + C8H9N02. Stadeler's hy- pothesis, that in the change to biliverdin, bilirubin takes up one molecule of water and one of oxygen (CieHigNgOs HoO + O^CisHgoNoOj) is no longer tenable. By the action of dry bromine vapour upon dry biliverdin, and subsequent heating of the product to 100° in a current of dry air, Thudichum has obtained a monobrominated product, CgHsBrNOj. This compound is perfectly black, insoluble in ether, and only slightly soluble in alcohol. When biliverdin is dissolved in caustic soda and exposed to the action of sodium amalgam, a change is brought about which has not yet been precisely ascertained. 1 See Chem. News, May 12, 1876. ^ Journ. Chem. Soc, July 1876. BILIVEEDIN AND BILIFUSCIN. 105 The product, however, which is termed hydro-bihverdin, is distinct from a compound produced similarly from bilirubin. An ammoniacal solution of biliverdin is not precipi- tated by calcium or barium chloride ; but the acetates of lead, silver, and mercury yield precipitates in an alcoholic solution of the colouring matter. Bilifuscin (C9HnN03)(?). — To obtain this pigment, gall-stones may be powdered and extracted, first with ether, then with very dilute acid, as preliminaries to extraction by absolute alcohol. The bihfuscin dissolves in the boilins; alcohol to a brown colour. It is insoluble in water, ether, and chloroform, but is soluble in alkalies, and reprecipitated by hydrochloric acid in brown flakes. It furnishes calcium and barium combinations by precipitation of its ammoniacal solution with the respec- tive chlorides of these metals. Its precise formula is yet doubtful ; Stadeler regards it as bilirubin plus one molecule of water ; but as his formula for bihrubin is wrong, dependence cannot be placed upon that for bilifuscin. Other Biliary Pigments. — Bihprasin is said to be ob- tained by extracting inspissated bile or gall-stones succes- sively with ether, hot water, chloroform, dilute acid, and boiling chloroform ; the residue on extraction with alcohol takes up biliprasin to a green colour. Bilihumin is left in the residue after the extraction of the foregoing pigment. According to Thudichum a number of other colouring matters which may be spectroscopically identified are to be found in certain diseased processes terminating in the production of calculi. 106 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. Other Constituents of Bile. — The only remaining con- stituents of bile are lecithin and choline ; the one is a phosphorised and aniidated fat, the other is the ammo- nium-base it yields on decomposition. As we shall have to enter more fully into the study of these principles in treating of brain chemistry, their consideration is reserved till then. THE LIVER. 107 CHAPTEK VIII. THE LIVER ; ITS FUNCTIONS. GLYCOSURIA AND DIABETES. In Chapters YI. and VII. we have studied the nature and chemistry of that liquid the secretion of which con- stitutes the principal function of the liver, and in our present study it will be important to bear in mind what is taught in Chapter IX. regarding the presence of sugar in the blood. The liver is the largest glandular organ in the body, being from 50 to 60 ounces in weight, and consisting of cells Avhich seem to be the seat of its specific functions. It is supplied with blood vessels and bile ducts, inter- spersed with lymphatics and nerves. Fat and bilirubin may be contained in it, and it also furnishes albumin, mucin, glycogen, sugar and biliary acids. When re- cently extracted from the body, the liver presents an alkaline reaction, but becomes acid on standing. Boil- ing water extracts from the liver, lactic and volatile fatty acids, inosite, xanthine, hypoxanthine, uric acid, and leucine. Its ash furnishes potassium and phosphoric acid. There are various diseases of the liver, the best known being so called degeneration, or ' bacony liver,' but of the chemical causes underlying it, or of the chemical interpretation to be placed upon it, we are without knowledge. 108 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. There can be no doubt that the principal function performed by the liver consists in the elaboration of bile and its secretion. This elaboration is effected from the constituents of the blood which is presented to the liver, but we are totally ignorant of the profound changes which must constitute this important process. The whole process is controlled and regulated no doubt by the nervous system, a fact which A. Socoloff has brought to bear in explanation of some otherwise uninteresting experiments detailed^ by him. The author found that the secretion of bile is distinctly increased by tlie intro- duction of glycocholate of sodium into the stomach or blood, but from a further consideration of these and other results, he concludes that the phenomenon is one of peculiarly nervous origin, and due in the particular in- stance cited to the irritating properties of the biliary acids. Socoloff's paper is characteristic of many others of a like kind, and equally worthless ; so worthless indeed that we shall disregard them, and for this reason. Between the methods of experiment having themselves no safe warranty of employment, and the results, there is no direct connection ; it is impossible to reason from effects to causes, or vice versa, and as the methods of experi- ment are generally ill-considered, and the results misun- derstood or misinterpreted, it is best to leave them out of consideration. As regards, therefore, the production of bile from the elements of the blood we know at pre- sent no more than the fact. It has been thought that the Hver is one source of the colourless corpuscles of blood, but here again w^e are ^ Pfl tiger's Archiv.fur Physiologie, xi. 166-177. GLYCOGEN. 109 ■without absolute knowledge. We therefore pass on to consider a further function known to be resident in the liver. Bernard and Hensen discovered in the liver a kind of dextrin of the formula CgHioOg, and they concluded that it was produced through a decomposition of albumin exerted by that organ. Subsequently, it has been ascer- tained by Dr. M. Foster, Bernard, Pavy, and others, that a similar amyloid matter is found in other forms of life (Entozoa, larvse of flies, solidified lung of pneumonia, &c.) accumulated in structures having one feature in common with the Hver, namely a limited supply of oxygen, Pavy has used this fact as an argument in theories which we must hereafter consider, but for the present it cannot be regarded as decided whether this character in common is anything more than the utmost accident. More espe- cially must this precaution be observed since glycogen has been stated also to occur in the transversely striated muscles. Abeles found ^ this substance also in the spleen, lungs, and kidneys of dogs fed exclusively for some days previous on bread. The characters of glycogen are very simple ; when dry it is a yellowish-white powder, but it may take up one or two molecules of water, and become gummy. Its aqueous solution polarises light to the right four times as intensely as dextrose sugar. In alcohol it is insoluble. With iodine it gives a violet or maroon-red coloration. Its aqueous solution dissolves oxide of copper, but exer- cises no kind of reducing action on the potassio-tartrate of copper. When boiled with dilute acids, or when 1 Chem. Centr. 1876^ 230. 110 ORGANS, FLriDS, ETC,, 00XCER5ED IX DIGESTIOX. subjected to the action of saliva, pancreatic juice, serum of blood, or cold prepared extract of liver, it is transformed into glucose by the assimilation of a molecule of water. It is readilv prepared by minring a fresh liver and boiling with water, filtering, and pressing. The filtrate is then concentrated and precipitated with much strong alcohol, when yellowish-white flocks are thrown down, consisting of impure glycogen. It may be purified by boiling with caustic potash, dilution with water, and reprecipitation by absolute alcohoL Or the glyc-ogen may be precipitated &om the concentrated aqueous extract of hver by means <^ glacial acetic add. As r^ards the precise method by which the liver elaborates it from the blood, little definite knowledge is possessed. But from what has been ascertained it may be fonned from albumin alone, although with fowls a mixed didt of starchy and albuminous matters is most &vouiable to its production. Numbers of researches bearing upon this question have been published, but in most of them it is impossible to draw any definite conclusions from the experiments described. S. WoUTbeig has discussed^ the whole ques- tion, and after reviewing the views and experiments of Bernard, Voit, Pettenkofer, Vallentin, Bauer, Bock, and oth^iB, amcludes from his own investigations that gly- cogen is an intermediate decomposition product of albu- min in the smimal organism. In connection with this view it may be interesting to bear in mind two fects, viz., that the liver undoubtedly produces bile by the de- composition of albumin, and that certain albuminoids, PRODUCTIOxV A^'D DESTl.NT OF GLYCOGEN. Ill (such as chondrin) yield glucose when decomposed by hydrating agents (see Chapter on Albuminoids). J. Forster ^ finds that when sugar is injected into the veins of dogs which have been kept without food for several days, the amount of glycogen in the hver is increased. It cannot be supposed that glycogen is formed in the economy from sugar, and J. Forster concludes that the increase of glycogen arises from an increased decomposi- tion of albuminoids brought about through the sugar. Thus it arises that one of the points at issue between those experimentalists who have devoted time to this matter is this : is glycogen formed directly from bodies introduced with the object of increasing its amount (as maintained by Pavy and others), or do these substances only contribute indirectly by being themselves oxidised, and thus protecting the glycogen from change, as main- tained by Tieffenbach and Weiss and others ? V. Mering- attempts to decide this question, and he has found that the assimilation of a number of substances such as grape-sugar, cane-sugar, milk-sugar, fruit-sugar, inulin, hchenin, glycer- ine, arbutio, gelatin, and albuminates, produces a consi- derable accumulation of glycogen in the hver. On the other hand he found that inosite, mannite, quercite, erythrite, and fats failed to behave in the same way. To sum up this part of our subject, it may be said that of the his- tory of the production of glycogen we do not know sufficient to decide precisely regarding it. Opinion is by no means unanimous either as to the final destiny of liver glycogen ; some physiologists main- tain that it passes from the liver in an unaltered state, 1 iV. Eep. Pharm. xxr. 773-739. * Pfliiger's Archiv. f, Physiologie, xiv. 274-284 112 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. and is finally oxidised in the circulation, while others hold that it is changed while yet in the liver into sugar, and this passing by the hepatic vein into the system becomes oxi- dised. This latter view is supported strongly by Bernard, and to a large extent has been adopted by physiologists who wTite of the ' glycogenetic function of the liver.' This theory certainly derives weight from the fact that dead liver is capable of quickly converting glycogen into sugar. Pavy, however, who ardently supported it at first, became the first to as strenuously oppose it on the alleged ground that no sugar is made in the liver in health. Nevertheless some sugar can be found in hepatic blood, and it has been shown by Thudichum^ that Pavy's experiments are by no means conclusive. According to Tiegel, the blood corpuscles undergo disintegration in the liver, yielding a ferment which trans- forms starch into sugar, but v. Wittich has shown ^ that even serum yields such a ferment by extracting its alco- holic precipitate with glycerine. He has also obtained a diastatic ferment from the parenchyma of the liver when it has been quite freed from blood. It oppears to be formed in the cells, and is partly poured out with the bile. W. Epstein and J. Mliller^ seem to have confirmed in some measure the experiments of v. Wittich. Liebig showed that the liver itself, when finely minced and suspended in w^ater, ferments and evolves carbonic dioxide and hydrogen, and Bechamp has re- peated and extended these observations, and has shown that the same occurs even when the liver has been ^ Thudichum's Chemical Physiology, p. 8. 2 Pfluger's Archiv. vii. 28-32. 3 Deiit. Chem. Ges. Ber. viii. G70-682. DIABETES MELLITUS. 113 washed in water containing phenol. Bechamp also show^ed that the fermentation is independent of the presence of micrococci and bacteria, and W. K. Yasnopolsky^ has con- firmed these views. So that altogether it seems to be fairly established that the liver contains certain active ferments ; it also produces glycogen, which admits of being changed into sugar by means of the said ferments. We must now apply this knowledge in attempting to explain an artificial form of diabetes termed glycosuria, and the true disease itself On the theory that sugar is formed in the liver and oxidised in the blood, a lack of oxidising power was conjectured to constitute the disease known as diabetes mellitus, since in this disease, sugar is voided in the un- changed state. EoUo alleged^ that 'this disease consists in an in- creased morbid action of the stomach with too great a secretion, and an alteration in the quality of the gastric fluid, producing saccharine matter by a decomposition of the vegetable substances taken in with the food, which remains unchanged.' Others, however, and among them Dr. BailHe, maintained that the morbid action resided in the kidneys; but Eollo argued that from their very nature these organs are incapable of forming sugar, simply acting as separating agents ; he yet allowed that they might become morbid through an increased activity and sympathy to which they may be subject in such a disease, and he thus explained a fact he himself observed, viz., that in certain cases the urine contains more sugar than the blood. In consonance with these views, sugar-form- 1 Pfluger's Archiv. xii. 78-86. ^ Eollo on Diabetes Mellitus, p. 387. 114 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. ing foods were avoided in the treatment of the disease, while such oxidising agents as potassic chlorate and nitric acid were recommended for administration. We pause here, to remark how characteristic such reasoning as this is, even in these days, of some medical men who fail to perceive the common requirements of logi- cal science. Assuming that by means of oxidising agents all the sugar existing in the blood admits of oxidation, it by no means follows that because the sugar is thus de- stroyed, the causes of its formation are also removed, for its formation is the revealing characteristic of the disease ! Moreover, it is very doubtful whether the sugar which may be present in the blood can be oxidised in this way. Dr. Day, of Geelong, has recommended peroxide of hydrogen for this purpose, although he admits that it does not remove the causes of the disease. We know nothing of what relief it may afibrd to sufferers, but it certainly does not appear to act by virtue of its oxidising powers over sugar. This the writer has ascertained for himself, at least so far as regards the diabetic sugar present in urine, and what holds good with urine most probably is true of the blood. ^ But to return from this digression. With the view of testing the prevailing theory of diabetes. Dr. A. Dupre made some experiments which were published at the time in the Practitioner. He ad- ministered known amounts of fruit-sugar (in the form of honey) to a diabetic patient, and estimated the sugar voided in the urine. In this way it was shown that all the fruit-sugar contained in the administered honey was oxidised in the system ; it therefore becomes clear that ' Chemistry of Diabetes MellituSf by C. T. Kingzett. Chetn, Xetcs, vol. xxxii. p. 184. DUPEE OX DIABETES. 115 diabetes is not to be explained as due to a lack of oxidis- ing power in the blood. Dupre went further than this in his conclusions ; he thought his results pointed to the conclusion ' that the sugar found in the urine has not pi-e- viously existed ready formed in the blood, but has been formed only in its passage through the kidneys.' The correctness of the first conclusion is supported by Bernard's observation, that an artificial diabetes (gly- cosuria of Pavy) can be developed in dogs and rabbits by irritation of the fourth ventricle of the brain with a needle, whereby sugar is developed in the blood, and passed in the urine. The other conclusion is by no means so clear ; Leh- mann and Dupre both found that the percentage of sugar in the blood in cases of diabetes generally amounts to 0*04 per cent, only, a quantity not comparable to that excreted in the urine, but nevertlieless such a conclusion is in opposition to all our knowledge of the functions of the kidneys. Moreover, other observers differ from Leh- mann and Dupre in their determinations of the sugar present in diabetic blood ; thus Thudichum found in one case as much as 2 per cent, sugar. Dr. Dalton also de- termined the amount of sugar present in a normal liver immediately after removal from the body at 0*25 per cent. That diabetes is an exceedingly ill-understood disorder is evident from other points of view. For instance, Dupre observed that the administration of sugar in his experi- ments caused a decrease in the amount of urea secreted, a fact previously noted by F. Hoppe.^ In this disease, also, lactic acid has been alleged to make its appearance 1 Arch.f. Path. Anat. x. pp. 144-169. I 2 116 ORGANS, FLUIDS, ETC., CONCERNED IN DIGESTION. in the saliva, and aceton in the stomach and urine ; as regards aceton, however, this is more than doubtful, be- cause the tests employed in its detection are tests also for alcohol. Glycosuria may be variously produced. Thus Wick- ham Legg found that if the ductus choledochus of a cat were tied, while no sugar was found in the urine within five or six days after puncture, yet without tying the duct, glycosuria commenced within an hour after punc- ture. Afterwards v. Wittich found that the tying of the duct diminished the amount of glycogen in the liver, and caused glycosuria. In an endeavour to account for this fact observed by v. Wittich, experiments were made by E. Kulz and E. Frerichs,^ and their results were claimed by them to show in common with previous experiments by Legg, that it was due to the hver not producing more glycogen beyond what existed at the time of tying. Bernard's observation of the causation of glycosuria by a nervous interference paved the way for other dis- coveries of a similar nature. Thus Pavy found that a division of certain parts of the sympathetic system oc- casioned the presence of sugar in the urine. In his more recent researches^ Pavy condemns, on the basis of experi- ment, Schiffs hypothesis, in which the escape of sugar from the liver, and incidentally, the production of glyco- suria, are supposed to be brought about by the develop- ment of a ferment in the blood flo"vving to the liver as a result of the hyper^emia which succeeds those operations on the nervous system which give rise to artificial dia- * Pfliiger'g Archiv. f. Physiohgie, xiii. 460-468. • Proc. Roy. Soc. to], ixiii. p. 539, and vol. xxiv. p. 51. GLYCOSUKIA. 117 betes. In some experiments upon dogs, Pavy has found that when defibrinated arterial blood is injected into the mesenteric vein, sugar is developed in the circulation ; in the urine the sugar amounted to from 10 to 15 grains per fluid ounce. Inasmuch as venous blood fails to produce these results, Pavy concludes that the production of gly- cosuria through influences on the nervous system is due to a vaso-motor paralysis affecting the vessels of the chylo-poietic viscera, by which process the blood reaches the portal system without having been de-arterialised. Pavy finds the support of his theory in the results of ex- periments in which animals were made to breathe oxygen ; in several experiments upon dogs saccharine urine was thus developed, but oth-er experiments, however, failed in this respect ; so also with frogs the results were partly negative although chiefly affirmative. Tieffenbach had pre- viously determined that artificial respiration with air is sufficient to produce glycosuria, and Pavy confirms this observation, as also one made previously by Dr. Eichard- son and by Schmiedeberg to the effect that inhalation of carbonic oxide produces a hke result. A similar action of puff-ball smoke is explained by Pavy as due to its contained carbonic oxide ; it should be remarked, how- ever, that the physiological effects of pure carbonic oxide are totally distinct from those of puff-ball smoke. In explaining the power of oxidised blood to con- vert the glycogen of the liver into sugar, Pavy looks upon this event as only a part of the whole truth, nor does he regard the action as due directly to the oxy- gen in the blood, but rather to the action of the de- arterialised blood as a ferment. Pavy's theory is in no wise deserving of full credence. In the first place he 118 OKGAXS, FLUIDS, ETC., CONCERNED IN DIGESTION. is credited with having sho^vn that temporary glyco- suria can be induced by impeding respiration, and unless it can be shown that in such case, blood reaches the liver in an arterial condition (an incomprehensible result), the fact, if true, is directly opposed to his more recent experiments above described, raid irreconcilable with the conclusions he has drawn from them. Again, if oxygen in the blood gives rise to a ferment, then carbonic oxide, acting (as Pavy says it does) like oxygen, must give rise to a ferment also ; but on chemical grounds it is at once seen that the ferments (if such exist at all) cannot be identical ; hence the production of glycosuria by the two agents must be brought about in different ways in the two instances, and then again such cases of artificial diabetes must be explained differently to the ordinary disease of that name. Pavj^'s conclusions admit of experimental criticism as follows : If glycosuria be due to the transformation of amyloid substance into sugar through the agency of a ferment present in oxidised blood, then if this dextrin- like body be isolated (as it can be) and treated with arte- rial blood out of the body, it should give rise to the for- mation of sugar. The same result should be attained by ])lood saturated with carbonic oxide. But even if affirma- tive results w^ere attained, they would be of little value if the statement be true, as alleged, that blood serum contains a ferment possessing this power. If blood serum contains such a ferment, or if the liver contains one (and both are said to), then the amyloid substance, both in health and during diabetes, should be transformed into sugar ; in truth, such appears to be the case, the difference being that in health the sugar is oxidised in the blood, DIABETES NOT UNDERSTOOD. 119 whereas in diabetes and glycosuria it is voided in an unchanged state. Thus, in spite of all the researches which have been made on these vexed questions, we are left without ' a plausible theory or a rational treatment of diabetes ' (Thudichum). Organic diseases affecting the brain and spinal cord, external injuries to the brain, and certain in- fluences on the sympathetic nervous system, are known often to precede diabetes, and perhaps to lead to it, and these observations, supplemented by Bernard's famous, and Pavy's skilful experiments, would seem to indicate that diabetes, as we recognise it in its chief characteristic (the presence of abnormal quantities of sugar in the blood and urine), represents a factor of interference of the proper functions of the blood, as governed solely by the nervous system. It becomes therefore of great and necessitated importance, that research should be directed to the chem- ical and anatomical investigation of the brain and other nervous centres in cases of death from diabetes mellitus. The disease seems to exist in many forms which may or may not be related to the same original causes, but in the foregoing remarks the subject has been treated as a whole for the sake of convenience, and in order to carry out the more immediate object of this work, viz., the appli- cation of chemical science to physiology and pathology. PART III. NUTRITION ; OE ' ¥OEK AND WASTE CHYLE. CHAPTEE IX. CHYLE, LYMPH, AND BLOOD. CHYLE. Chyle is tlie digested fluid absorbed by the lympliatics — or lacteals, as they are called — of the intestines. These lacteals form networks in the walls of the small intestine, and send blind prolongations into the little processes termed villi. The lymphatics have trunks which lead through the mesenteric glands and discharge themselves into the receptacle of the chyle, a dilated part of the lower end of the thoracic duct. The chyle is ultimately poured into the general circulation near the junction of the left internal jugular and subclavian veins. A large part of the chyle, while yet in the intestine, is absorbed directly into the blood-system. It constitutes the fluid which yields to the blood all those matters which are necessary to maintain all parts of the body in a proper state of nutrition, and to atone for those pro- cesses of work and waste which we shall see hereafter constitute the essential conditions of life. It is an opalescent creamy-looking fluid, deriving its yellowish white or slightly red colour from the suspension of fatty matters in the form of an emulsion. It also contains fibrin, or a form of principle immediately ante- cedent to fibrin ; hence, after removal from the body, it speedily coagulates in the same way as blood. Chyle is of an alkaline reaction and a saline taste, and contains 124 NUTRITION ; OR ' WORK AND WASTE.' potassium- albumin, casein, and seralbumin, also lactates, sugar, urea, and alkaline salts, besides white and red corpuscles. It has been conjectured that these corpuscles form in certain lymphatic glands through which the chyle passes, as already explained. It appears that the amount of fibrin increases as the chyle reaches that point wliere it is discharged into the blood; hence it is supposed that in its passage, it is gradually formed from the albumin present. The following analyses^ express the general compo- sition of chyle in full digestion and while fasting : — Water . In Full Digestion. 91-8 Fasting. 96-8 Solids . 8-2 3-2 Fibrin • •2 •09 Albumin 35 2-30 Fats y-3 •04 Extractives . Salts . •4 •8 1 Hensen has published- the following analyses of supposed chyle obtained on different days from a lym- phatic fistula : — Water . . . 910 Albumin . . 1'7 Fat . . . 0-28 Alcoholic extractives 0021 Water extractives 0'104 Cholesterine . . 0018 Ash . . . 0^643 Iron (mean) . . 00022 90-3 3-9 mean 3^15 3-G9 0-183 1-04 0-102 1-09 mean 0-7G8 It cannot be said that human chyle has been properly examined, but few opportunities presenting themselves for effecting its complete study. Chyle may be regarded as dilute and imperfectly formed blood ; thus, while the 1 Ralfe's Fhysiological Chemistry (authors not given). "^ Pfliiger's Archiv.f. Physioloffie, x. 94-113. LYMPH. 125 blood of a horse contains 22 per cent, solid matter, its chyle furnishes only from 4 to 9 per cent, solid matter. No fibrin is found in the chyle as it is absorbed by the lacteals of the intestines, an observation which lends probability to the view already expressed, that it is formed in its passage to the thoracic duct from the soluble albu- minous principles present. Among the extractives not only urea, but leucine and tyrosin are stated to have been found. The ash resembles that of blood, and yields chiefly potas- sium salts ; phosphate, carbonate, and chloride of sodium being also present as well as a little calcium and magne- sium. Before entering the blood, chyle is always mixed with a considerable amount of lymph, and Bidder has calcu- lated from some experiments on animals, that in an adult man there are discharged from the thoracic duct into the subclavian vein about 6'6 lbs. of true chyle mixed with 22 lbs. of true lymph in twenty-four hours. The emulsive state in which the fat exists in the chyle has been alluded to under the processes of digestion. In certain diseased processes — for instance, chylous urine — a persistence of fatty emulsion is observed in arterial blood, and occurs also in the disease cited, in the urine. LYMPH. Lymph may be regarded as transuded serum of blood which has been reabsorbed from the tissues, and carried back to the circulation by the lymphatics. Like the blood, it is alkaline, and consists of a plasma and cor- puscles which, however, are all white ; it contains about 5 per cent, solid constituents, and is, indeed, diluted blood-serum, from which the tissues have already taken 126 NUTRITION ; OR ' WORK AND WASTE.' what they require for their proper nouiishment. Tlie serum of blood contains about 8 per cent, sohd matters. It is calculated that a quantity of fluid equal to that of the blood is pom-ed daily from the lymphatic system into the former. Lymph constitutes a clear, nearly colourless, or straw- coloured fluid, and of composition very like to that of chyle, except that it contains less fibrin and fatty matter. Its fat occurs in the form of globules, and its ash presents a further difference from that of chyle by having a pre- dominance of sodium salts ; it also contains lactic acid. For the purposes of ordinary study, it may be obtained from a blister, but its whole constitution is not well known by reason of the difficulty experienced in obtaining sufficient quantity in a healthy state. In scrofula and tuberculosis, both lymph and chyle are often deranged simultaneously with the diseased glands, and Thudichum states it is probable that improper nutrition has the main share in causing these diseases in many children. BLOOD. Of the nutrient fluids contained in the body, blood is from every point of view the most important. Elabo- rated from the food by virtue of the digestive and other processes already described, it serves to supply to the body fresh material in place of that which is worked up — worn out — by the processes of life. It also dissolves and carries aWay those products which result from the processes just alluded to, and it is through the blood that the great process of oxidation by respiration is effected. Blood consists in 1000 parts of about 795 water and 205 solids, these latter being made up, as might be con- jectured from the known composition of chyme and THE CONSTITUENTS OF BLOOD. 127 chyle, of albumin, fibrin, colouring matter containing iron, fatty matters, extractives, and salts. But inasmuch as it constitutes the drainage-system of the body also, or the stream which absorbs the effete products of life-changes, these latter are also contained in it and complicate its constitution. Owing, however, to our imperfect know- ledge of the real steps involved in the wear and tear of the animal tissues, it is difficult to say in regard to some of the blood constituents which are principals and which are excrementitious. Blood is of an alkaline reaction and sahne taste, with a specific gravity ranging between 1050 and 1060. As it exists in the body, it has a temperature of 36*5° to 37 "8° C, a fact which will require more particular study hereafter, in considering the meaning of vital force ; it is sufficient here to remember that animal heat is primarily due to the process of oxidation which is incessantly going on in the human economy. The temperature of the blood is not uniform throughout the body ; that of the hepatic and portal veins has a higher temperature than ordinary venous blood, a state of things referable probably to more active local oxidation (see ' Functions of the Liver,' Chap. VIII.); the blood in the right ventricle is also warmer than that in the left one. The difference between arterial and venous blood is slight as regards the composition ; the former contains more water and fatty matter. But there is a more vital difference between the two, consisting in the different degree of oxidation — a state of the blood which depends upon the presence in it of the red colouring-matter (hsemato-crystalline), containing iron, of which more anon. The coao^ulation of the blood which occurs after it has been removed from the body, and which sometimes 128 NUTRITION ; OR ' WORK AND WASTE.' happens in disease to a smaller extent during life, is a phenomenon not yet satisfactorily explained. It will be studied more in detail hereafter. Besides the various albuminous matters present in blood, viz., fibrin, albumin, globulin, and the colouring- matter ho3mato-crystalline, it contains oleic, stearic, lactic, hydrochloric, phosphoric, and sulphuric acids ; these are more or less in combination with sodium, potassium, ammo-, nium, calcium, and magnesium. The fat present in blood amounts to about 2 per cent., and it contains also soaps or saponified fats. The blood also contains a little choles- terine and a phosphorised body identical with one of many similar principles contained in the brain, but different from that apparently present in the bile. The blood also contains a little nitrogen in a dissolved state, and oxygen ; but the oxygen is mainly held in a sort of combination with the colouring principle. Again, the carbonic acid given off at all points of the body is held in the blood partly in a dissolved state and partly as carbonate of sodium. It is intended to study hereafter the chemical con- stitution of the corpuscles of blood, but it should be stated here, that beyond their own chemical constituents, a certain amount of a matter called stroma is present, and it is this which is supposed to give shape to the corpuscles. Stroma is not albuminous in nature, being soluble in ether, alcohol, and chloroform ; but it contains a small amount of fibrino-plastic substance, termed para- globuhn by Schmidt. The total amount of blood contained in the body varies with the time and each person, and is difficult to estimate, but ordinarily it appears to amount to about one-tenth of the body-weight. Bischoff has more recently COMPOSITION OF THE BLOOD. 129 determined the quantity at 7"7 per cent, of the weight of the body. J. Steinberg^ has determined the absokite mass of the blood in various animals, and he gives the following table showing the relative weights of the blood and of the bodies of the animals from which it was derived : — Eabbits 1 : 12-3-13-3 Guinea pigs . 1 : 12-0-12-3 Dogs .... 1 : 11-2-125 Puppies 1 : 16-2-17-8 Oats .... 1 : 10-4-11-9 Oats fasting . 1 : 17-8 Kittens .... 1 : 17-3-18-4 According to Schmidt and Lehmann,^ the following tables represent the composition of blood-corpuscles and liquor sanguinis, but how far these were perfectly sepa- rated from each other, and without prejudice to their relative compositions, it is difficult to state. Specific gravity of blood corpuscles, 1"0885 1000 parts contain — Water . . 688-00 Solid constituents 312-00 containing Hematin .... 16'75 „ „ „ „ Globulin and cell membrane 282-22 )) JJ V }> ^^^ ^'^l „ „ „ „ Extractive matters . . 2"60 „ „ ,, ,, Mineral substances , . 8-12 312-00 Tbe mineral matters include Chlorine .... 1-686 n V Sulphuric oxide (SO3) 0-066 )} » Phospboric anhydride (P2O5) 1-134 )y }J Potassium .... 3-328 V V Sodium .... 1-052 )> )) Oxygen .... 0-667 » V Oalcic pbosphate . 0-114 )f )) Magnesic „ . . . 0-073 8-120 1 Pfliiger's ArcMv. vii. 101-187. ^ Miller's Organic Chemistry, 3rd Edit. p. 870 K i;30 NUTRITION ; OR ' WORK AND WASTE. Specific gravity of Liquor sanguinis 1"028 1000 parts contain — Water . 902-UO Solid con-"! ^ > 9rl0 consisting of — stituents J 1000-00 Fibrin . . 4-05 Albumin . . 78*84 Fat. . . 1-72 Extractive matter 8'94 Mineral substances 8*55 consisting of — Chlorine 97-10 . 3-G44 Sulphuric oxide (SOj) 0115 Phosphoric anhy- dride (PoOj) Potassium Sodium . Oxygen . Calcic phosphate Mao-nesic „ 0-191 0-323 3-341 0-403 0-311 0-222 We also take from tlie same source as furnishes the two foregoing tables, the next seuting, according to Becquerel and Eodier, composition of blood in man and in woman :- 8-550 that which one, repre- the average ■Woman. Specific gravity of defibrinated blood .... 10600 1-0.575 Specific gravity of serum . 10280 10274 Composition — Water .... . 779-00 791-10 Fibrin .... 2-20 2-20 Serolin- .... 0-02 0-02 Phosphorised fat . 0-49 0-46 Cholesterine . 0-09 0-09 Saponified fat . 100 1-05 Albumin . 69-40 70-50 Blood corpuscles . 141-10 127-20 Extractive matters . 6-80 7-40 100000 1000-00 » This may be disregarded. It is a name given to a substance which has never been analysed, and it may be included in that with which it is probably identical, viz. fat, in some form or other.— Author. BLOOD OF DIFFERENT ANIMALS. 131 Sodic chloride . , Man 3-10 Woma 3-90 Other soluble salts . 2-50 2-90 Earthy phosphates . 0-33 0-35 Iron in terms of metal . 0-57 0-54 6-50 7-69 The extractives consist of sugar, urea, kreatin, krea- tinin, lactic acid, uric acid, hippuric acid, leucine, tyrosin, xanthine, and hypoxanthine. G. Bunge has recently published^ some interesting analyses of the blood of pigs, horses, and oxen, which we reproduce here. I. Depibeii^ated Pig's Blood. Per 1000 parts of blood corpuscles. Per 1000 parts of serum. "Water . 632-1 Water . 919-6 Solid constituents . 367-9 Solid constituents Albumin 80-4 Haemoglobin . 261-0 67-7 Albumin . 86-1 Other organic substances 50 Other organic substances 12-0 Inorganic substances 7-7 Inorganic substances 8-9 Potash . 0-273 Potash . 6-543 Soda . 4-272 Magnesia 0-158 Lime . 0-136 Chlorine 1-504 Magnesia 0-038 Phosphoric acid . 2-067 Oxide of iron 0-011 Chlorine 3-611 Phosphoric acid . 0-188 II. D EFIBPvINATEI ) Horse's Blood. Per 1000 parts of blood co rpuscles. Per 1000 parts of serum. Water . . 608-9 Water . . 896-6 Solid constituents . 391-1 Solid constituents . 103-4 Potash . 4-92 Potash . 0.27 Chlorine . 1-93 Soda . 4-43 Chlorine 3-75 1 Zeits chriftf. Bio logie, xii. 191-216. s. 2 132 NUTRITION ; OR ' AVORK AND WASTE.' III. Defibrinated Ox Blood. Per 1000 parts of blood corpuscles. Per 1000 parts of serum Water . . 599-9 Water . . 913-3 Solid constituents . 400-1 Solid constituents . Albumin . 86-7 Haemoglobin . . 2S0-5 . 73-2 Albumin . . 107-3 Other organic substances . 5-6 Other organic substances 7-5 Inorganic substances 7-9 Inorganic substances 4-8 Potflsh . Soda . 0-254 Potash . 0-747 4.351 Soda . 2-093 Lime . 0126 Magnesia 0-017 Magnesia 0045 Chlorine 1-635 Oxide of iron 0-011 Phosphoric acid 0-703 Chlorine 3-717 Phosphoric acid . 0-266 The liquor sanguinis means serum holding fibrin in solution ; serum being that part of the blood which is left when the fibrin, enclosing in its meshes the corpuscles, has been separated by spontaneous coagulation. The serum produced by whipping blood is a less perfect one, inasmuch as it contains more corpuscles than the former one. The mixture of fibrin and corpuscles which forms on spontaneous coagulation is often named cruor or crassamentum. The serum produced in this last-mentioned process is a straw or faintly-red coloured transparent liquid, ex- ceedingly liable to putrefaction. Its composition is tolerably well expressed by the tables given above, after deducting the fibrin included in the liquor sanguinis. Among its albuminous constituents exists paraglobulin, fibrinogeneous matter, and some sodium-albumin or se- rum-casein, as it has been designated, and a little potas- sium-albumin. Seralbumin proper, however, enters most largely into its albuminous constituents ; while fibrin, which is a more complicated body than albumin, is THE SUGAR PEESENT IN BLOOD. 133 supposed to be produced in coagulation (Schmidt) by the action of paraglobuUn upon fibrinogeneous substance. Blood in life contains rather less than half its own volume of gaseous matter, consisting of oxygen, carbonic acid, and nitrogen. Of the Sugar present in Blood. — That sugar is a normal constituent of blood might be inferred from a knowledge of the various processes occurring in the digestive apparatus, which result in the transformation of starchy matters into sugar. For the detection of this principle in the blood there are several methods more or less reliable. One recommended by Bernard consists in making the blood into a paste with animal charcoal, addition of a little water, and filtration. The filtrate should be colour- less, and Trommer's test for sugar may be then applied to it. In another method, the blood is precipitated with much alcohol, and the precipitate extracted with toler- ably strong spirit ; from the combined solutions the alcohol is distilled off, and the residual watery solution tested for sugar. Both these methods remove albumin and colouring matter, and some other matters which might interfere with tests for sugar. Moore's test is only reliable when the sugar is present in considerable amount ; it consists in boiling a solution (after applying one of the two foregoing methods to blood) with strong potash or soda, when the presence of sugar is revealed by a colour which is first yellow, then reddish, and finally black or brown. Bottcher's test consists in the addition of a pinch of oxide of bismuth or its subnitrate to the suspected solu- 134 NUTRITION; OR MVORK AND WASTE.' tioD, previously rendered alkaline by a large excess of potash or soda. The fluid, in the presence of sugar, becomes black or dark grey on boiling, owing to the reduction of the bismuth. The fermentation test for sugar is well known. A given quantity of solution is maintained in a suitable vessel at 35° C. in contact with a little yeast. Any carbonic anhydride which is evolved may be caught in baryta water, and the precipitate of baric carbonate after- wards isolated, dried at 100°, and weighed ; while the alcohol, if any be produced in the solution, may be dis- tilled off, made up to the original volume of the solution employed, and its specific gravity taken. By these means the amount of sugar may be estimated. The alcohol may be detected qualitatively by adding a little potassic bichromate solution acidified by sulpliuric acid, and boiling ; alcohol turns the solution green by reduction. Sugar may be estimated by the ordinary process, which consists in the reduction of a standard Fehling's solution, or by boiling with excess of Fehling's solution, and isolating the cuprous oxide thus formed, converting it into cupric oxide by ignition and weighing. Amount of Sugar present in Blood. — From the determinations made by Lehmann and Dupre, the per- centage of sugar present in normal healthy blood is extremely small, and generally amounts to O-O-l per cent, only. In a recent paper,^ C. Bernard shows that sugar is a vital constituent of blood, and exists in quantities varying from 1 to 3 parts per 1000. It rapidly disappears from tlie blood after death, and so also from blood which has 1 Ann. Chrm. Phys. [5], ix. 207-2.58. AMOUNT OF SUGAR IX BLOOD. 135 been withdrawn from the body. Thus Bernard found in the blood of a dog as much as 1-07 parts per 1000, immediately after drawing it from the body, but after standing five hours it had diminished to 0*44 parts per 1000, and after twenty-four hours it had totally dis- appeared. Bernard also shows that arterial blood con- tains more sugar than venous blood, as the following results indicate. Sugar per 1000 parts. Arterial Blood. Venous Blood. Dog (i) 1-45 . . 0-73 „ (ii) 1-24 . . 0-99 „ (iii) 1-17 . . 0-88 Finally, Bernard claims to have traced the production of the sugar found in blood to the liver, but of this part of the subject we have already treated. Since the publication of Bernard's paper, Dr. Pavy has communicated^ to the Eoyal Society two papers re- lating to the sugar found in blood and its determination. His method consists in properly preparing the blood by coagulation, filtration, &:c., and then boiling the solution with excess of potassio-tartrate of copper. The suboxide of copper thus obtained is oxidised by a few drops of peroxide of hydrogen, dissolved in nitric acid, and from this solution the copper is electrolytically deposited on a platinum spiral and weighed. It is only the appli- cation of this method that Dr. Pavy can claim as new, and indeed barely that, inasmuch as chemists have long been acquainted, and have used every particular in this method. Pavy then claims to have demonstrated that- — 1000 parts of dog's blood contains an average of 0-787 parts sugar. 1000 „ sheep's „ „ „ 0'521 „ „ 1000 „ bullock's „ „ „ 0'543 ,, „ 1 June 14 and 21, 1877. 136 NUTRITION ; OR ' WORK AND WASTE.' He contrasts these results with those obtained by Bernard and described above, and also states that he has observed no difference in the amount of sugar present in arterial and venous blood ; but he agrees with Bernard on the diminution and ultimate entire disappearance of the sugar in blood, after death or after withdrawal from the body. It is not possible to decide whether Bernard or Pavy is right in the matters where they disagree, until more Avork of a chemico-mathematical order shall be forth- coming. Blood Corpuscles and their Chemical Constitution. — The corpuscles of the blood are of a tw^ofold character, \iz., red and colourless, but the latter, while larger in size, are far less numerous than the former. The red corpuscles are flattened circular disks, having an avenige diameter of -3^\,-o of an inch, and a thickness of about one-fourth of this. From this it follows that more than 10,000,000 will cover only one square inch, and it has been calculated that a cubic inch of blood contains no fewer than 70,000,000,000 corpuscles. The colourless corpuscles have an average diameter of ^ Jq-q of an inch. The red corpuscles are soft, flexible, and elastic bodies, and are semifluid in the centre, where globulin is held in solution ; they derive their colour from a special substance found nowhere else in the body. By exposure tu carbonic anhydride, the red corpuscles swell out, while oxygen flattens them. Colourless corpuscles are constantly vibrating ; ' under- going active contraction, or being passively dilated by llie contraction of other parts.' ^ ^ Huxlev, Lessons in Elementary Physiology, p. G3. THE CHEMISTRY OP BLOOD-COEPUSCLES. 137 It appears certain that the red corpuscles are in some way or the other derived from the colourless ones, but the exact changes and steps have not been ascertained ; even the origin of the colourless ones is not known, although it is supposed that they are formed in the duct- less glands, and pass as lymph corpuscles into the blood. The colourless corpuscles increase in number after eating, and diminish between the meals. The corpuscles of blood, which are heavier than the plasma, are best isolated by treating defibrinated (by whipping) blood with its own volume of a solution of common salt consisting of a saturated solution diluted ten times. The mixture is stirred, and then put on one side to settle ; when the corpuscles have deposited, the super- natant liquor is decanted, and the deposit washed by decantation with a similar solution of salt, and in this way the corpuscles are obtained free from serum. They consist of stroma or colourless skeleton containing hsemato- cryptalliue (h^emaglobulin), a little cholesterine, a phos- phorised body, paraglobulin, and salts consisting chiefly of potassic chloride and sodic phosphate. The stroma is insoluble in water and salt, but easily soluble in ether, chloroform, and alkalies ; so that, when washed corpuscles are shaken up with water and ether, the stroma, cho- lesterine, and fatty matters are taken up by the ether, while the colouring matter of the blood is liberated and dissolves in the water. The filtered aqueous solution crystallises on exposure to a temperature of — 5° to — 10° C, but sometimes it is necessary (for instance, when the blood is from birds) to add alcohol before crystallisation ensues. The deposit from the blood of man, the ox, and sheep is, however, amorphous, but in every case it 138 NUTRITION ; OR ' WORK AND WASTE.' consists of hsematocrystalline. The cholesteiine may be extracted from the corpuscles separated from the blood as described, by means of alcohol ; it is easily recognised, and is accompanied by a phosphorised body. Hoppe- Seyler has estimated that the corpuscles present in 100 cc. of blood contain 004 to 0-06 grm. cholesterine. Blood- crystals from man consist of four-sided prisms with dihedral summits, and when from other animals they are also of a rhombic character, but the precise form differs. These crystals contain 0*4 3 per cent, iron, and ana- lyses invariably lead to an atomic weight for the molecule of 1 3,280, and to the formula CeooHgeoFeNis^SyOiyy. Hsemato- crystalline is insoluble in alcohol, chloroform, ether, benzene, and other solvents, but readily soluble in water and alkahne solutions. Notwithstanding the large size of the molecule of htematocrystalline, there appears to be little doubt of its individuality, inasmuch as the percentage of iron is a constant, and its other properties confirm the fact. It contains, therefore, or consists of the following proximate principles : an albuminous substance which, when separated, is amorphous and colourless, and a crys- talline body named hematine. Of the first of the sub- stances nothing is known, but many researches have been made relative to the second. To obtain it in a crude state, the process of Wittich is most applicable, and this consists in treating blood "with seven times its bulk of a cold solution of potassic carbonate, containing one part by weight of the salt in two parts of water. The mixture is filtered through calico, then pressed and afterwards heated with alcohol to free it from the excess of potassic carbonate, and then dried. It is now extracted with alcohol at 40° C, and the extracts are treated with an HEMINE A^^D HEMATITE. 139 equal volume of absolute alcohol containing tartaric acid in solution. In this way the potash is precipitated, and the hemine remains dissolved, but is precipitated on cooling (after concentration of the filtrate) in minute bluish black crystals consisting of rhombic plates. Thudichum and Kingzett^ have analysed these crystals and obtained from them their proximate constituents, for as thus isolated they are not constituted of one individual substance. Synopsis of Analyses, (a) (6) (c) Iron . . . . 7'677 7-625 Chlorine . . . 2-98 3-08 3-005 Phosphorus . . . 0-6666 ■ 0-6105 0-6479 Now hemine, as this substance is termed, has been considered as a hydrochloride of hematine, but these analyses of a perfectly crystalline substance show that the substance cannot be regarded as a chemical individual, but as a mixture of two or several matters. From the fact of its taking up hydrochloric acid when exposed to a current of that gas, it is seen that ' hemine ' must contain free hematine. Preyer in his treatise on blood-crystals states that hemine dissolves in nitric acid with decomposition, and that ammonia throws down white hydrated ferrous oxide from the yellowish solution. This statement, in itself incredible, because ferrous oxide cannot exist in a nitric acid solution, is shown by Thudi- chum and Kingzett to be incorrect in its entirety. Preyer must have mistaken the precipitate yielded by mere dilu- tion of the nitric acid solution for one yielded by ammonia, because the precipitate is entirely soluble in excess of ammonia and contains the original amount of iron. ^ On Hemine, Hematine, and a Phosphorised Siihstance contained in Blood Corpuscles. Jeurn, Chem. Soc, September 1876. 140 NUTRITION; OR 'WORK AND WASTE.' C. Paquelin and L. Jolly, ^ in a paper on the colouring matter of blood, have stated that it does not contain iron. In former papers they claimed to have demonstrated that the iron present in blood corpuscles exists as tribasic ferrous phosphate, and in the paper cited they undertake to substantiate their former proposition. Thudichum and Kingzett have repeated the experi- ment of Paquelin and Jolly, but with no confirmation of their results. The errors of the French chemists are made perfectly manifest, and other important results are established. Thus it is shown that by acting upon hemine with a mixture of acetic and citric acids under the con- ditions stated by Paquelin and Jolly, its composition is not affected ; but by extracting it with benzene and acetic acid, a certain amount of hematine goes into solution, while the larger quantity remains undissolved, and is freed from the phosphorised impurity by means of the benzene which dissolves the latter. The undissolved portion in fact proved to be probably the purest hematine ever made, and gave on analysis the formula C32H32FeX406. The benzene and acetic acid extracts, after freeing from benzene by distillation, left a black viscous matter which proved mostly soluble in hot absolute alcohol, and deposited therefrom on coohng in a perfectly white form. Its alcohoHc solution gave combinations with platinum chloride, cadmic chloride, and lead. The cadmic chloride salt was recrystallised from alcohol and analysed, when the fact of its identity with one of the phosphorised con- stituents of brain-matter was established. This is shown by the following comparison of the analytical figures. 1 Compt. Rend. 79 (1874), 918. PHOSPEORISED PRINCIPLE FROM BLOOD. 141 Phosphorised Principle from Blood Corpuscles Phosphorised Principle from Brain ' 0. . . 64-90 . . 64-06 H. . . 11-65 . . 11-30 N. . P. . 0. . , . . . 3-30 . . 4-42 . .16 72 . 3-11 4-15 . 16-78 The cadmic chloride compound gave the formula C,6H,e4N3P,0,,.2(CdCl,). This is the first time that the isolation and analysis of any definite phosphorised principle of the blood has been effected ; at the same time the method of isolation would not preclude the presence of yet other similar compounds (see 'Brain Chemistry' hereafter). To return to the consideration of hematine, it will be seen that the formula of Thudichum and Kingzett is C32H32FeN4^06. Hoppe-Seyler, after abandoning several varieties of formulse, now gives CsiHg^N^FeOg, but the afore-named chemists, in a criticism of his analytical results, show that this formula is not absolutely trust- worthy. Thus he found an excess of nitrogen for his theory, and explained it as due to an absorption of ammonia from the air while washing on a filter. This could not be, for so sensitive is hematine to ammonia, that the presence of mere vestiges in the air causes hematine at once to dissolve and to pass through the filter. It is revealed by its colour, and may be reprecipi- tated by a trace of acetic acid. The colouring-matter of the blood has had assigned to it so many names^ as also those proximate principles which are derived from it as described, that it will be ^ Report Medical Officer of the Privy Council, &c., New Series, No. iii. (1874), 174. 142 NUTRITION; OR 'WORK AND WASTE.' best to present the facts in a form which will enable the memory to retain a true regard of their position. Ha3matocrystalline or haimoglobulin is the colouring matter of the blood; the formula for it is CeooHycoFeNis^SgO,;;. This consists of hematine and albuminous matters. From the blood there may be obtained hemine, a substance primarily consisting of hematine, but containing also hydrochloride of hematine and a phosphorised principle. When hemine is submitted to the process described by Thudichum and Kiugzett, pure hematine is obtained from it of the formula C32H32FeN40o, and the phosphorised principle is isolated in a pure state, and found to be iden- tical with one present in brain-matter. General Characters of Hematine. — Hematine is in- soluble in water ; it is also insoluble in ether when neutral, and but slightly soluble in alcohol. It readily dissolves in caustic alkalies, particularly ammonia, and also in acid or alkaline alcohol. Hoppe-Seyler has assigned the name haemato-pop- phyrin to a substance said to be free from iron and obtainable from hematine by treatment with strong sulphuric acid, but no proof of this fact has ever been presented, that is to say it has never been shown by analyses that the preparation is free from iron. The same author also states ^ that by the action of tin and hydrochloric acid and other reducing agents upon an alcoholic solution of hematine, a yellow colouring matter is obtained agreeing in properties with the urobilin of Jaffe and the hydrobilirubin of Maly. Hoppe-Seyler heads his paper ' Formation of the Colouring-matter of » Deut. Chem. Ges. Ber. vii. 10G5. COLOURING MATTERS FROM BLOOD AND URINE. 143 Urine from Blood,' but for such a title there is no justifi- cation. The urobilin of Jaffe is a mixture and has never been analysed ; the hydrobilirubin of Maly, whatever it may be, is not yet estabhshed ; Hoppe-Seyler gives no analysis of his product. Indeed, in regard to the many mere statements made of late years by various authors relative to the assumed identity of colouring-matters present in the blood, the bile, and the urine, it may be said with all justice that such identity has not received a single analysis in its favour or a single proof of its truth. It is for similar reasons that many papers bearing on physiological chemistry, but totally unsupported by analytical data, are not noticed in this work. A. Bechamp,^ for instance, has described a process for obtaining hematine in a pure and soluble form, but that his product is pure is not sustained by any analytical or other evidence. Defibriuated blood is mixed with water and precipitated by lead acetate, and basic lead acetate containing 10 per cent, of solution of ammonia, successively. The filtrate, yet containing the blood pig- ment, is freed from lead by carbonic anhydride or car- bonate of ammonium, and dried at 35° to 40°. The garnet-coloured laminee contain a little ammonium car- bonate, acetates of the alkahes, and probably urea. To free from these, the red solution after the basic lead pre- cipitate, is mixed with half its volume of 50 per cent, alcohol, and is then again precipitated with ammoniacal lead acetate. The brick-red precipitate is isolated, washed with 40 per cent, alcohol (out of contact with carbonic anhydride), mixed with water, a little ammonic 1 Ann. Chim. Phys. (5) iii. 340-342. 144 NUTRITION; OR 'WORK AND WASTE.' carbonate added, and then decomposed by means of carbon dioxide ; the filtered solution coagulates at 61°, and must be dried below that temperature to obtain the ' pure solid pigment.' But what is meant by * the pure sohd pigment,' and what it is, is not shown. Alex. Schmidt^ asserts that the colouring-matter of the blood has nothing to do with its coagulation, but tliat this has its source entirely in the protoplasm. Hema- tine and hiemato-crystalliue occur in the urine in cruentu- resis (paroxysmal haimaturia) ; while a diminution of hasmatocrystalline in the blood constitutes the disease termed ' chlorosis ' or ' anemia.' The Coagulation of Blood. — Of all the properties exhibited by blood, the most remarkable, perhaps, is its power of coagulation. This act generally sets in after the blood has been removed from the body, in from four to five minutes, but it is retarded by exposiu-e to a low temperature, and when kept at if will not coagulate at all ; it is accelerated by an increase in temperature, taking place most readily at about 38° C. The coagu- lation is prevented by allowing the blood to flow from the vein into alkaline solutions, or concentrated solutions of various salts, such as potassic nitrate or sulphate and acetate of sodium. In certain cases of sudden death, the blood also appears to lack its power of spontaneous coagulation. Contact of the blood, as it is withdrawn fi'om the body, with non-Uviug matter promotes coagulation, wdiile direct contact of living matter retards or entirely prevents its coagulation. Thus, if it be kept in a portion of a vein ' Pflug-er's Archiv.f. Phjs. ix. 353-357. THE COAGULATION OF BLOOD. 145 tied at both ends, it remains fluid for a long time. Still more remarkable is the fact that blood not only is not coagulated when poured into the excised heart of a turtle, but solidified blood becomes fluid again under these con- ditions and remains so, as long as the heart lives, which it does for some hours or days after excision. The living surfaces of blood-vessels are therefore the agencies which preserve the fluidity of the blood ; but as yet we do not even know the rationale of the process of coagulation. It is certainly known that when blood is allowed to stand it becomes solid, and the solid matter thus coao-u- lated encloses in its meshes the blood-corpuscles. The same solid substance is obtained by whipping the newly- drawn blood, and may be obtained white by washing with water to free it from blood-corpuscles. This sub- stance is called fibrin, and fibrin appears to be a more complex substance than seralbumin, since, on the one hand, it seems to be elaborated from albumin, and on the other hand, to yield that substance under certain slight decomposing influences. But what is not yet decided is this : has the fibrin existed previously in the blood in a state of solution, or is it a synthetical product under changed conditions? The most acceptable explanation of the coagulation of the blood originated with Alex. Schmidt. He supposes that blood contains two sub- stances, viz., fibrino-plastic substance or paraglobulin, contained in the serum and corpuscles, and fibrinogen also contained in the serum and other fluids of the body ; he further supposes that these two substances have the power of combining to form fibrin. Now it is quite true that in a sense such substances may be isolated and behave as indicated when they are brought together, L 146 NUTRITION; OR 'WORK AND WASTE,' The globulin or paraglobulin of blood-corpuscles, when added to serous infusions (such as hydrocele fluid or fluid of pericardial, pleural, or peritoneal exudation) developes fibrin. It does so chiefly in a w^eakly alkaline solu- tion ; strong acids and alkalies completely suspend its action, but it does not lose its power by drying or keeping in alcohol. The substance contained in the serous infusions, and upon which the paraglobulin acts, may also be isolated ; but what is yet wanted before this hypothesis of the cause of coagulation of blood can be accepted, is the establishment of accurate formulas for the tw^o substances supposed to be concerned, and the further })roof of their combination in molecular pioportions. It is possible that the paraglobuhn acts as a ferment by contact action, but whatever be the explanation, another explanation must be provided to show why coagidation does not occur in the living blood-vessels. In another paper,^ A. Schmidt claims to demonstrate that the colourless corpuscles of the blood constitute the true soui'ce of fibrin ferment, or rather that tliey become so as soon as the blood has left the body ; at the same time he states that coagulation is attended with the de- struction of white corpuscles. In a yet later paper ^ it is stated that the ferment is present in all cells which contain protoplasm ; these include lymph, chyle, and pus cells, and perhaps connective tissue generally. The same author has also given further information regarding the coagulation of fibrin in yet another paper,^ But in op- position to these views, Olof Hammersten ^ contends that 1 PaUgers Archil', f. PJnjs. xi. 515-577. ^ Compt. Bend. Ixxxiv. 78-80. 3 Compt. Mend. Ixxxiv. 112-115. * Pfluger's Archiv.f. rhys. xiv. 211-273. THE COAGULATION OF BLOOD. 147 paraglobulin does not unite with fibrinogen to form fibrin, nor become in any way converted into fibrin. He gives experiments in support of his views, but it is quite unnecessary to consider them at all in detail, for the reason why we have so briefly condensed other papers bearing upon the subject of coagulation, viz., that the authors have dealt with substances which cannot be defined by analytical figures, and that chemico-mathe- matical considerations are not included in their researches ; so that it is never known what it is precisely they have experimented upon, nor is it possible to place a fair inter- pretation upon their views, except in the most general manner. We must now give some attention to a more .recent view of the causes of the coagulation of blood. E. Mathieu and V. Urbain have stated ^ (in 1873), that when egg albumin is deprived of the carbonic anhj^dride it contains, by means of the exhaust (mercury) pump, it also loses certain volatile salts, viz., ammonium carbonate, and traces of sulphate and sulphide, and that in this con- dition it is not coagulable even at 100° ; the deprivation of albumin of its salts they state to convert it into globu- lin. These statements, in themselves utterly inacceptable to chemists, were reiterated^ in a subsequent paper, and while it was again stated that the cause of the coagulation of blood is the presence of carbonic acid, it was said that this latter may be removed by exosmose, and that its effects may be neutralised by neutralisation with an alkali. In opposition to these views, A. Gautier^ made a 1 Compt. Rend. Ixxvii. 706-709. "^ Jom-n. Pharm. Chim. (4) xx. 337-345. 3 Compt. Rend. Ixxx. 1360-1363. L 2 148 NUTRITION; OR 'WORK AND WASTE.' number of experiments confirmative of tlie view that the deatli of the blood is essential for coagulation, and dis- proving the hypothesis of Mathieu and Urbain. It may here be stated also that on the publication of these papers, Dr. Thudiclium, in conjunction with the author of this work, made a number of experiments, and repeated those of Mathieu and Urbain, and it appeared from these that the new view of tlie causes regulating the coagulation of blood was utterly without founda- tion. M. F. Glenard also described^ experiments to the same effect. To this latter chemist, Mathieu and Urbain replied,^ describing a few experiments in which it was demonstrated that exposure to carbonic anhydride deter- mined the coagulation of the blood, even when kept in contact with the segment of a blood-vessel. The best answer, however, to these experiments, is the fact that blood does not coagidate in life under conditions where carbonic acid is certainly present in the blood-system. To sum up these observations, it may be admitted that so far, no perfectly acceptable explanation has been given of the cause of the coagulation of blood. The Albuminous Principles contained in Blood. — The serum of the blood contains, as already stated, a modifi- cation of albumin termed seralbumin ; this is present to the extent of 7 to 9 per cent, in the serum, which also contains a small amount of paraglobulin. It also con- tains sodium-albumin and a little potassium-albumin. The paraglobulin, or fibiiuo-plastic substance, may be precipitated from serum, after dilution with ten volumes of water by means of carbonic anhydride ; while the 1 Compt. Rend. Ixxxi. 102-103. ^ jj^i^ 535-536. ALBUMINOUS PKIKCIPLES IN BLOOD. 149 alkaline albuminates are precipitated on addition of a little acetic acid. Seralbumin is completely precipitated by boiling in the presence of a little acetic acid also, but if no acetic acid be present, sodium-albumin remains dissolved. The fibrinoo;enous matter of the serum is deposited in an adhesive form, after removal of the paraglobuhn, by dilution and exact neutralisation with acetic acid. Fibrin produced by spontaneous coagulation or whipping of blood is supposed to result from the action of paraglobulin upon fibrinogenous matter. Fibrin is characterised by certain definite properties which are easily demonstrated. Thus if it be kept moist and in a warm place, it gradually liquefies (Liebig) and decomposes after the manner of putrefaction, evolving butyrate and valerate of ammonium ; but the most remarkable fact is, that albumiu appears to be produced, and may be identified by its coagulable and other properties. Ammonic sulphide is also formed. Its ultimate products of decomposition are similar to those of albumin. Fibrin dissolves in dilute caustic potash at 60° C, and in the filtrate, acetic and phosphoric acids produce precipitates soluble in excess of the acid. If boiled with caustic potash, fibrin evolves ammonia, and potassic sulphide is formed in the solution. Concentrated hydrochloric acid, aided by warming, dissolves fibrin to a violet-coloured solution : nitric acid turns it yellow and dissolves it. Tannic acid precipitates it from its solutions, and per- oxide of hydrogen is decomposed by it ; this latter pro- perty is particularly distinctive. InO NL'TRITIOX ; OR " WORK AND WASTE.' The Blood in Disease. — The blood presents an ex- pression of the whole state of the body ; combining in one the elements of nutrition and excrementation (to some extent), and presenting the powers which enable the greatest process of life, viz., respiration, to be carried on. It is the feed-stream and the sewage- system at once of the human economy, and hence its composition is affected by every change in health or disease. Thus in fevers, cholera, diarrhoea, and the like diseases, the amount of water in the blood is diminished, from the fact that a greater wearing down of the solid tissues is experienced ; in gout, uric acid occurs as urates of sodium and calcium ; in diabetes, tlie amount of sugar present is abnormally high ; in jaundice, biliary colouring matters are found present ; while formic acid occurs in leukocy- thaemia. In certain diseases, Thudichum has found free fatty acid in the blood, emulged by the sodium phosphate which it contains. Thudichum has also shown, in a research upon cholera (published in the ' Eeports of tlie Medical Officer of the Privy Council '), that in this disease, the serum of the blood exhausts water and other matters from the blood- corpuscles, which latter henceforth cease to be carriers of oxygen. In yellow fever some of the colouring-matter of the blood decomposes and colours the skin yellow ; while in paroxysmal cruenturesis it appears in the urine as a red matter. In cases of poisoning by arseniuretted hydrogen, serpents' bites, or sulphuretted hydrogen, prussic acid, ammonia, &c., the colouring matter of the blood is also seriously affected, but in what precise manner is unknown. BALANCE OF BODY-WEIGHT. 151 CHAPTER X. NUTRITION OR ALIMENTATION. The processes of life are sustained and kept in order by means of the food which we take into our mouths, and which is prepared for assimilation by the various pro- cesses of digestion already studied. The chyle is the fluid by means of which the blood is kept constantly supplied with new matter, to be afterwards absorbed by the body in place of those parts broken down by every act of life. In this way a man of average size and activity must take into his body 8,U00 grains of chemically dry solid matter, if he is not to gain or lose in body weight. The blood also absorbs through the lungs about 10,000 grains of oxygen, making a total daily gain of 18,000 grains, or nearly 2^ lbs. avoirdupois of solid and gaseous matter.^ The alimentary canal excretes not more than 800 grains of dry solid matter in the same period, and it therefore follows that 7,200 grains of solid matter must pass out of the body in other forms as well as the 10,000 grains of oxygen. These 17,200 grains of matter pass out of the body through the breath, the sweat, and urine. Of course the matters which leave the body are not identical in nature with those substances absorbed in the body, but they constitute the effete changed sub- ^ Huxley's Elements of Physiology, p. 138, 1st edit. 152 JsTTRITIOX ; OR 'WORK AND WASTE.' stances resulting from tlie metamorphosis of animal tissue. Food therefore is substance which, when introduced into the body, and modified by the processes of digestion, serves for the renewal of body structure, or for main- taining vital action. Some foods, being nearly identical in nature with some of the substances entering into the constitution of the tissues, require but little change before being capable of assimilation. Other foods are not as- similated in the sense that their substance is taken up by, and becomes part of the tissues, but serve other functions equally important. Xo one food serves to supply all the materials required by the body, but they differ in value according to the degree in which they supply one or more requirements. The mass of the body consists of various forms of albuminous principles ; these are built up in the body by a re-arrangement of allied principles taken in the food. The fat which we eat is not supposed to give rise to the whole amount of f\it in the living tissue, but is what is termed a respiratory food, being oxidized in the blood — an act which is attended with the generation of force, ordinarily viewed as heat, but not necessarily so. The fat present in the body tissues is supposed to be derived in some w^ay from saccharine food, and in part from nlbu- niinous substances. In experiments made by Gundelach and others, it was found that bees fed exclusively upon sugar secreted wax in abundance ; about 20 lbs. of sugar being consumed while 1 lb. of wax w^as being produced. The principles of the brain and nervous system ap- pear to be built up, at least for the most part, by syn- thetical processes occurring in the body, but otherwise unknown at present. The various secretions of the tody FOODS. 153 are produced by acts of decomposition which will receive special consideration hereafter. Everywhere in the animal economy mineral matters are found either in the free state or associated in combination with organic principles. The bones and teeth in particular contain a large propor- tion of earthy matters, and hence it is necessary that our food should include matters from which a proper supply of these substances is obtainable. The nitrogenous parts of the body are in the main derived directly or indirectly from the vegetable kingdom (as elsewhere pointed out), and in a large measure there- fore the vegetable is constructive, while the animal is both constructive and destructive. While life maybe maintained for a greater or less length of time by a restricted number of kinds of food, perfect health and unimpaired functions are best secured and maintained upon a mixed diet comprising all the matters — nitrogenous, saccharine, amyloid, and saline — which are available for sustenance. The idea of f:)od is too often identified with solid matters of which we partake, but in truth, air and water are as necessary foods as any others. Moreover, there are many kinds of food which, while they are not absolutely necessary, are not therefore harm- ful when partaken of in proper amount ; these may be considered as luxuries, but they are nevertheless foods. Among this class of bodies we have alcohol, which must be placed side by side with fat as a respiratory food, or a substance which admits of oxidation in the lungs. Every act of life, be it one of thought, will, conscious- ness, or work, is attended by the consumption of matter in the body. That is to say, all work done signifies some- thing destroyed or changed. It is difficult to decide in 154 NUTRITION ; OH ' WORK AND WASTK.' many cases wliether tliese changes — geuerally of oxida- tion take place in the tissues themselves or in the blood ; but be it one or the other, the same necessity exists for food, which must take the place of matter used up in previous acts of life. This is as essential to life as is the supply of oil to a lamp which is required to give light. Starch and sugar are substances which require a deal of oxviien to burn them into carbonic anhydride and water. C«H,o05 + 0,, = 6C0., + 5II..0 C,,H,,Oi, + 0,, = 12C6,, + 11H,0 It will be seen from these equations that starch and sugar contain in themselves sufficient oxygen to burn their hydrogen into water, but that required by the carbon is supplied in the lungs from the air inspired. Fats, however, require far more oxygen than starch and sugar, because they do not contain even enough oxygen for the combustion of the hydrogen present in them. So also with the fatty acids into which and glycerine, fats are resolved (at least in part) in the processes of digestion. This may be instanced with stearic acid derived from the tristearine of mutton fat. C^gllaeO, + 0,, = 18C0,, + 18H,0 From the fact that oxidation in the lungs is a process of combustion, and the source of muscular power, the foods which undergo this process are termed heat pro- ducers ; but we shall see presently that it is by no means clear that blood oxidation is attended directly with the evolution of animal heat. In his work on ' Practical Hygiene,' Parkes quotes the figures of Moleschott in illustration of the amount of DIETARY VALUES OF FOODS. 155 food required by an adult man of average weight — 140 lbs. — who occupies himself in moderate work. These are as follows : — Dry Food. Ounces. Grains of G-rains of Nitrogen. Carbon. Albuminous substance . . 4-587 . 317 . 1073-6 Fatty „ . 2-964 . nil . 1024-4 Oarboliydrates . 14-257 » • 2769-4 Salts .... . 1-058 j> 22-866 With this knowledge it is easy to calculate the dietary values of different kinds of food from their ascertained composition. The following table for calculating diets is taken from Hassali's work on Food.^ Food Water Albumi- nates Fats Carbohy- drates Salts Raw leau mi-at . 75 15 8-4 _ 1-6 Fattened meat 63 14 19 3-7 Roast meats (including drip- ping) .... 54 27-6 15-45 — 2-95 Bread 40 8 1-5 49-2 1-3 Flour ..... 15 11 2 70-3 1-7 Biscuit 8 15-6 1-3 73-4 1.7 Eice 10 5 0-8 83-2 0-5 Oatmeal .... 12 16 6-8 63-2 2-0 Maize 13-5 10 6-7 64-5 1-4 Dry peas .... 15 22 2 63 2-4 Potatoes .... 74 1-5 0-1 23-4 1 Carrots (no cellulose in- cluded) .... 85 0-6 0-25 8-4 0-7 Cabbage .... 91 0-2 0-5 5-8 0-7 Butter 8-8 2-7 85 — 3-5 Eggs (less shell) . 73 5 13-5 11-6 1-0 Cheese .... 36-8 33-5 24-3 5-4 Milk of specific gravity 1030 86-7 4 3-7 5 06 Sugar 3 — — 96-5 0-5 Dr. Hassall describes the use of this table as follows : — ' The quantity by weight of any of the articles enumerated being known, the amounts of the albuminates, fats, and ^ The table is, however, mainly taken from Dr. Parkes' work. 156 NUTRITION; OR 'WORK AND WASTE.' carboliydrates are easily calculated by a simple rule-of- three sum. Thus, supposing the allowance is 12 oz. of meat, one-fifth must be deducted for bone ; the water in remaining 9'6 oz. will be ascertained as follows : 75x9-6 ^^ ^ and so on for the other constituents.' Food, then, serves two main purposes : (a) to keep up the supply of force which may be registered, and is generally spoken of, as animal heat ; and {h) to restore matter lost to the body by acts of life. The following table ^ shows the amount of heat generated from ten grains of certain different foods during their complete combustion within the body. The figures themselves were worked out by Frankland, to ^vhose experiments we sliall further allude hereafter : — Food. In combustion raises WTiich is eqiial to lbs. of water 1° Fahrenheit, lifting lbs. 1 foot high. 10 grains dry flesh . 13-12 . . 10,128 „ albumin 12-85 . 9,920 ,, lump sugar 8-61 . 6,647 „ arrowroot 10-06 . 7,766 „ butter . 18-68 . . 14,421 „ beef-fat 20-91 . . 16,142 During sleep the vital action is low and tolerably unifomi, but after partaking of food it is high and vari- able. As the amount of vital change proceeding in the body may be greater at some times than at others, it necessarily follows that a proportionate quantity of food will be required. The next table, which is also taken from Ed. Smith's * Taken from Edward Smith's work on Foods. II. S. King & Co., 1873. AMOUNT OF Am INSPIRED. 15: work ' On Foods,' shows the relative amount of air inspired during varying degrees of exertion : — The lying posture being 1 „ sitting „ is 1-18 Eeading aloud or singing .... „ 1-26 Tlie standing posture „ 1-33 Railway travelling 1st class „ 1-40 „ „ 2nd „ . . . „ 1-5 ,, „ upon the engine at 20 to 30 miles per hour „ 1-52 Railway travelling upon the engine at 50 to 60 miles per hour ..... „ l-5o Railway travelling in 3rd class . „ 1-58 „ „ upon engine, average of all speeds ....... „ 1-58 Railway travelling upon engine at 40 to 50 miles per hour ...... „ 1-61 Railway travelling upon engine at 30 to 40 miles per hour ...... „ 1-64 Walking in the sea „ 1-65 „ on land at 1 mile per hour „ 1-9 Riding on horseback at the walking pace „ 2-2 Walking at 2 miles per hour „ 2-76 Riding on horseback at the cantering pace . „ 3-16 Walking at 3 miles per hour „ 3-22 Riding moderately ..... „ 3-33 Descending steps at 640 yards' perpendicular per hour ....... „ 3-43 Walking at 3 miles per hour and carrying 34 lbs „ 3-5 Walking at 3 miles per hour and carrying 62 lbs „ 3-84 Riding on horseback at the trotting pace „ 4-05 Swimming at good speed .... „ 4-33 Ascending steps at 640 yards' perpendicular per hour ....... „ 4-4 Walking at 3 miles per hour and carrying 118 lbs „ 4-75 Walking at 4 miles per hour „ 6-0 The tread-wheel, ascending 45 steps per minute . „ 6-5 Running at 6 miles per hour „ 7-0 From the same series of experiments Smith determined the same effect, by showing the amount of carbonic acid evolved by respiration per minute : — . 4-5 grains . 4-99 . 5-7 . 504 . G-1 . 18-1 . 28-83 158 NUTRITION; OR 'WORK AND WASTE.' In profound sleep, lying: posture In lip-ht sleep Scarcely awake, 1 i a.m. '>+ Walking at 2 miles per hour )» ^ )> >> u Tread- wheel, ascending 28"15 feet per minute 43-36 „ The necessity for constantly renewing the protein matter, arises from the fact that the excretion of urea and Other nitrogenous decomposition products of albumin is an ever-occurring process during hfe, no matter how extreme the inactivity. Indeed, protein, or flesh-forming food, is the only one absolutely necessary, in addition to mineral salts, for the continuation of life, inasmuch as it con- tains plenty of carbon and hydrogen to support animal heat also ; but, for reasons to be immediately considered, it is better to take a mixed diet. If the food supply be deficient in nitrogen, the body begins to undergo a pro- cess of starvation — nitrogen starvation ; and in such case the body feeds upon its own tissues until the failure of this supply and the action of induced secondary causes, puts a stop to life. The advisability of a mixed diet is well stated by Huxley^ as follows : ' A healthy full-grown man, keeping up his weight and heat, and taking a fair amount of exercise, eliminates 4,000 grains of carbon to only 300 grains of nitrogen, or, roughly, only needs one-thirteenth as much nitrogen as carbon. However, if he is to get his 4,000 grains of carbon out of albumin, he must eat 7,547 grains of that substance. But 7,547 grains of albumin contain, 1,132 grains of nitrogen, or nearly four times as much as he wants. Thus a man confined to a 1 Ulements of Physiology (Macmillan & Co.), 1866, p. 142. ADVANTAGES OF A MIXED DIET. 159 purely proteid diet must eat a prodigious quantity of it. This not only involves a great amount of physiological labour in comminuting the food, and a great expenditure of power and time in dissolving and absorbing it, but throws a great amount of wholly profitless laboiu- upon those excretory organs which have to get rid of the nitrogenous matter, three-fourths of which, as we have seen, is superfluous.' Hence, to avoid such an evil, experience teaches us to mix fats or amyloids with albuminous foods, and these, supplemented by the salts found in the body and furnished by vegetable and other matters, make up the total neces- sary foods for sustaining life. It is impossible here to discuss the relative value of foods, or the politico-economical aspects of the question, or the various influences exerted by age, time, climate, and other conditions upon the quantity or quality of foods required. These questions have been ably treated in separate treatises by Letheby, Smith, Hassall, and others, to which, excellent as they are, we must refer our readers. We, however, quote on the next page a table from Letheby's work ^ ' On Food,' showing the nutritive values of food. It should be stated that in the construction of this table Letheby has calculated the carbonaceous matters as starch, for the reason that the fattenincf and respiratory values of starch, gum, fat, &c., are very dif- ferent, as already explained. The power of fat is about 2*5 times that of sugar. To enter at all into the life history of tissues, — to attempt to depict the actual manner in which the hving 1 On Food, by Dr. H. Letheby, p. 5. BaiUiere, Tindall & Cox, 1872. 160 Iv'UTRITION : OR ' WORK AND WASTE. O '^ o > > H *5 a g 1 II -- t-, — 1 'i* X r. 2- '-"^ -+ (N O w t -+ O O O T cc X 6 6 X r? r: X i X X —1 o fri (M ic t^ to w c: "M c: i^ !>i c^j o — 1 <^j o o i^ i^ 1^: i X t>. c: t^ o t^ (N cb o «^- c^1 (f 1 1— 1 ■—1 1 6f^o6 1 Idb»b5.l>. X X O X p »p (fj Al CN C^ r^ r^ O . X t^ 6 6 6 1 1 1 «<© Ato & CO « -^ -^ o dc 6 6 ^1 1 «6»b-'bc^»b6 o ■a 1^- o c; X c; '^ c: "b oi -*00400COl>OX X -f - — ' xx6o 1 1 1 1 1 1 S o r-lXCOpOfT-CCp xocb^iX'^ic? r-l .-1 r-l Cq 1 -7^40-7^ 91 ,-^b,o-H C<1 r^ A( A-i 1 1 Tf 01 T»( Tjt 1 a t^lOOlO»0-^COOX»0 50fMi— ilOCCCOOXX Cti—ii— ir-ir-(i— 11— (1— II— it^xxc: irixoxx <0 . - " . . =i CO o -TS =2 iiT' a; - c c p < NUTEITIVE VALUE OF FOODS. 161 '^ O ,t,0»p(>Tt^ip(>TO(jqcqpiOC'10t;-iI OD OD OT r^ OD Ci cb ^ o o lo (N-^1— li— ll—ll— ll— I I— li— ICNi— II— li— li— lC.0 5ig ■^ "§ t^ o '^ =4-1 o a