IRLF MEMCAL Medical Library Exchange Library of the Medical College of Vir- ginia. r THE PHYSIOLOGY OF MAN; DESIGNED TO REPRESENT THE EXISTING STATE OF PHYSIOLOGICAL SCIENCE, AS APPLIED TO THE FUNCTIONS OF THE HUMAN BODY. BY AUSTIN FLINT, JR., M. D., PROFESSOE OF PHYSIOLOGY AND MICEOSCOPY IN THE BELLEVUE HOSPITAL MEDICAL COLLEGE, NEW YOBK ; FELLOW OF THE NEW YORK ACADEMY OF MEDICINE ; MEMBER OF THE MEDICAL SOCIETY OF THE COUNTY OF NEW YORK ; RESIDENT MEMBER OF THE LYCEUM OF NATURAL HISTORY IN THE CITY OF NEW YOEK, ETC., ETC. SECRETION; EXCRETION; DUCTLESS GLANDS; NUTRITION; ANIMAL HEAT ; MOVEMENTS ; VOICE AND SPEECH. XEW: D. ^PPLKTOX5: 90, 92 & 94 GRAND STREET. 1870. EOTERED, according to Act of Congress, in the year 1869, by D. APPLETON & CO., In the Clerk's Office of the District Court of the United States for the Southern District of New York. PEE FAG E. WITH the completion of this volume, all of the subjects belonging to human physiology, that are usually taught in medical schools or are treated of in systematic works, have been carefully considered, except the functions of the ner- vous system and the processes of generation and development. The first volume, published in 1866, treated of the blood, circulation, and respiration ; and the second volume, pub- lished in 1867, was upon the subjects of alimentation, diges- tion, absorption, and the lymph and chyle. The original plan of the work has been adhered to in the preparation of these three volumes, as each one constitutes a separate and distinct treatise, being complete in itself, while the full series is intended to cover the entire subject of human physiology. In recording the success of the parts already published, the author feels that his labors have been more than appreciated; and the friendly and encouraging criticism that the work has thus far received has stimulated him to increased efforts in the preparation of the present volume. Some of the subjects taken up in this volume have an especial interest to the author, from the fact that he has 44 4: PREFACE. investigated them by original experiments, and has suc- ceeded in developing new facts of a certain degree of value ; but it has been his endeavor not to give to these questions undue prominence, to the prejudice of other subjects of equal importance to the physiological student. The most promi- nent points developed by original investigation in the present volume are, the discovery of an excretory function of the liver, that had never before been described, and the mechan- ism of glycogenesis, a question that seems now to be defini- tively settled, notwithstanding the apparently opposite results obtained by different experimenters. Since the chapter on the glycogenic function of the liver has been printed, the author has seen an analysis of a series of observations on this subject, in which his conclusions with regard to the mechanism of the formation of sugar in the economy have been fully confirmed. The views embodied in this chapter, however, are entirely original, and were published in the New York Medical Journal in January, 1869.1 The confirmatory observations, by Tieffenbach, are also original, as far as any knowledge of this publication is concerned, and were published in the form of an Inaugural Dissertation, later in the same year.3 In laying claim to priority of publication, the author fully appreciates the im- portance of these independent experiments, by which the accuracy of his own researches have been so fully confirmed. 1 FLINT, Jr., Experiments undertaken for the Purpose of reconciling some of the Discordant Observations upon the Glycogenic Function of the Liver. — New York Medical Journal, Jan., 1869, p. 373. 2 TIEFFENBACH, Ueber die Existenz der glycogenen Function der Leber, Disser- tation, Konigsberg, 1869. — Zeitschrift fur rationelle Medidn, Leipzig u. Heidel- berg, 1869, Dritte Reihe, Bd. xxxv., S. 210. PREFACE. 5 "\Vith regard to the general mechanism of secretion, it has seemed important to the author to draw as closely as possible, the line of distinction between secretions proper and excretions; and our information with regard to the mode of formation of the secretions, and the production of excrementitious principles and their separation from the blood, is now of so positive a character, that we are able to subject these processes to pretty definite generalization. If we comprehend fully the mechanism of secretion and excretion, it is evident that our knowledge of particular fluids must be to a great extent based upon accurate proxi- mate analyses. The author has taken the greatest care in compiling the tables of composition of the various secretions and excretions, particularly with regard to the urine, having endeavored to make the table of its composition repre- sent as closely as possible the general process of disassimila- tion and its variations under physiological conditions. The author cannot but regard the description of the excretory function of the liver, with the discovery of the physiological relations of cholesterine, as of very great im- portance, in its relations to pathology as well as physiology. This subject has been elaborately considered in the chapter treating of the excretory function of the liver, and the views therein presented are put forward with more confidence, since they have been honored with a favorable report by a committee from the French Academy of Sciences? As the result of the author's investigations on this subject, it seems to be conclusively proven that cholesterine, under certain 1 ST. LAUGIER, Academic des sciences. Hole de la cholesterine dans Torganixme ; recherche* de M. AUSTIN' FLINT (fils). — Revue des cours scientifgues, Paris, 1868- 1869, tome vi., p. 495, and Comptes rendus, Paris, 1869, tome Ixviii., p. 1371. 6 PREFACE. pathological conditions, bears the same relation to disorgan- izing diseases of the liver that urea does to corresponding conditions of the kidneys. The experiments by which these facts have been developed are so repulsive and difficult that there is little likelihood of their being extensively verified ; and while the author confidently awaits the time when the results of his investigations will be generally admitted, he is satisfied at present with the acknowledgment that they are entirely original. Within a short time, several mooted points of great importance with regard to the physiological anatomy of the liver and the kidneys have been definitively settled. It is hoped that the chapters in which these anatomical questions have been considered will be found to represent the latest and most reliable views ; and it does not seem now that the conclusions will be materially altered by future researches. The author feels that he has no apology to make for the apparent delay in the issue of the present volume. His labor upon it has been almost unremitting since the issue of the volume on alimentation, digestion, and absorption; and his chief endeavor has been to make it represent faith- fully the existing state of the science, without sparing time or pains. All he can promise is, that the remainder of the work will be prepared with equal care, and, it is hoped, within a shorter interval. NEW YORK, September, 1869. 0 O3STTEJST TS. CHAPTER I. SECRETION IN GENERAL. General considerations — Relations of the secretions to nutrition — General mechanism of secretion — Differences between the secretions and fluids containing formed anatomical elements — Division of secretions — Mechan- ism of the production of the true secretions — Mechanism of the production of the excretions — Influence of the composition and pressure of the blood upon secretion — Influence of the nervous system on secretion — Excito- secretory system of nerves — General structure of secreting organs — Ana- tomical classification of glandular organs — Secreting membranes — Fol- licular glands — Racemose glands — Tubular glands — Ductless, or blood- glands — Classification of the secreted fluids — Secretions proper (perma- nent fluids; transitory fluids) — Excretions — Fluids containing formed anatomical elements, Page 13 CHAPTER II. SEROUS AND STNOVIAL FLUIDS — MUCUS — SEBACEOUS FLUIDS. Physiological anatomy of the serous and synovial membranes — Synovial fringes — Bursse — Synovial sheaths — Pericardial, peritoneal, and pleural secre- tions— Quantity of the serous secretions — Synovial fluid — Mucus — Mucous membranes — Mucous membranes covered with pavement-epithelium — Mu- cous membranes covered with columnar epithelium — Mucous membranes covered with mixed epithelium — Mechanism of the secretion of mucus — Composition and varieties of mu9us — Microscopical characters of mucus — Nasal mucus — Bronchial and pulmonary mucus — Mucus secreted by the lining membrane of the alimentary canal — Mucus of the urinary passages — Mucus of the generative passages — Conjunctival mucus — General func- tion of mucus — Xon-absorption of certain soluble substances, particularly venoms, by mucous membranes — Sebaceous fluids — Physiological anatomy 3 CONTENTS. of the sebaceous, ceruminous, and Meibomian glands — Ordinary sebaceous matter — Smegma of the prepuce and of the labia minora — Vernix caseosa — Cerumen — Meibomian secretion — Function of the Meibomian secretion, Page 39 CHAPTER III. MAMMAEY SECKETION. Physiological anatomy of the mammary glands — Condition of the mammary glands during the intervals of lactation — Structure of the mammary glands during lactation — Mechanism of the secretion of milk — Conditions which modify the lacteal secretion — Influence of diet — Influence of liquid ingesta — Influence of alcoholic beverages — Influence of mental emotions — Quantity of milk — Properties and composition of milk — Specific gravity of milk — Coagulation of milk — Microscopical characters of milk — Composition of milk — Nitrogenized constituents of milk — Non-nitrogenized constituents of milk — Inorganic constituents of milk — Variations in the composition of milk — Colostrum — Composition of colostrum — Lacteal secretion in the newly-born — Composition of the milk of the infant, . . . .72 CHAPTER IV. EXCKETION — ACTION OF THE SKIN. Differences between the secretions proper and the excretions — Composition of the excretions — Mode of production of the excretions — Discharge of the excretions — Physiological anatomy of the skin — Extent and thickness of the skin — Layers of the skin — The corium, or true skin — The epidermis and its appendages — Desquamation of the epidermis — Physiological anat- omy and uses of the nails and hair — Development and growth of the nails — Varieties of hair — Number of the hairs — Roots of the hairs, and hair-fol- licles— Structure of the hairs — Sudden blanching of the hair — Uses of the hairs — Perspiration — Sudoriparous glands — Mechanism of the secretion of sweat — Quantity of cutaneous exhalation — Properties and composition of the sweat — Peculiarities of the sweat in certain parts, . . .108 CHAPTER V. PHYSIOLOGICAL ANATOMY OF THE KIDNEYS. Situation, form, and size of the kidneys — Coats of the kidneys — Division of the substance of the kidneys — Pelvis, calices, and infundibula — Pyramids — Cortex — Columns of Bertin — Pyramidal substance — Pyramids of Ferrein — Tubes of Bellini — Cortical substance — Malpighian bodies — Convoluted CONTENTS. 9 tubes — Xarrow tubes of Henle — Intermediate tubes — Distribution of blood- vessels in the kidney — Vessels of the Malpighian bodies — Plexus around the convoluted tubes — Veins of the kidney — Stars of Verheyen — Lym- phatics and nerves of the kidney — Summary of the physiological anatomy of the kidney, Page 144 CHAPTER VI. MECHANISM OF THE FORMATION AND DISCHAEGE OF FEINE. Formation of the excrementitious constituents of the urine in the tissues, absorption of these principles by the blood, and separation of them from the blood by the kidneys — Effects of removal of both kidneys from a liv- ing animal — Effects of tying the urelers in a living animal — Extirpation of one kidney — Influence of blood-pressure, the nervous system, etc., upon the secretion of urine — Effects of the destruction of all the nerves going to the kidneys — Alternation in the action of the kidneys upon the two sides — Changes in the composition of the blood in passing through the kidneys — Physiological anatomy of the urinary passages — Mechanism of the discharge of urine, 162 CHAPTER VII. PROPERTIES AND COMPOSITION OF THE UEINE. General physical properties of the urine — Quantity, specific gravity, and reaction — Composition of the urine — Urea — Origin of urea — Compounds of uric acid — Hippurates and lactates — Creatine and creatinine — Oxalate of lime — Xanthine — Fatty matters — Inorganic constituents of the urine — Chlorides — Sulphates — Phosphates — Coloring matter and mucus - — Gases of the urine — Variations in the composition of the urine — Variations with age and sex — Variations at different seasons and at different periods of the day — Variations produced by food — Urina potus, urina cibi, and urina sanguinis — Influence of muscular exercise — Influence of mental exertion, . 186 CHAPTER VIII. PHYSIOLOGICAL ANATOMY OF THE LIVEE. Coverings and ligaments of the liver — Capsule of Glisson — Lobules — Branches of the portal vein, the hepatic artery and duct — Interlobular vessels — Lob- ular vessels — Origin and course of the hepatic veins — Interlobular veins — Structure of a lobule of the liver — Hepatic cells — Arrangement of the bile-ducts in the lobules — Anatomy of the excretory biliary passages — Vasa aberrantia — Gall-bladder — Hepatic, cystic, and common ducts — 10 CONTENTS. Nerves and lymphatics of the liver — Mechanism of the secretion and dis- charge of bile — Secretion of bile from venous or arterial blood — Quantity of bile— Variations in the flow of the bile — Influence of the nervous system on the secretion of bile — Discharge of bile from the gall-bladder, Page 232 CHAPTER IX. EXCEETOEY FUNCTION OF THE LIVEE. General properties of the bile — Composition of the bile — Biliary salts — Tauro- cholate of soda — Glycocholate of soda — Origin of the biliary salts — Choles- terine — Process for the extraction of cholesterine — Biliverdine — Tests for bile — Test for biliverdine — Test for the biliary salts — Pettenkofer's test — Excretory function of the liver — Origin of cholesterine — Experiments showing the passage of cholesterine into the blood as it circulates through the brain — Analyses of venous blood from the two sides of the body in cases of hemiplegia — Elimination of cholesterine by the liver — Analyses showing accumulation of cholesterine in the blood in certain cases of organic disease of the liver — Cholestersemia, 258 CHAPTER X. PEODTTCTION OF 8UGAE IN THE LIYEE. Evidences of a glycogenic function in the liver — Processes for the determination of sugar — Fehling's test for sugar — Examination of the blood of the portal system for sugar — Inosite — Examination of the blood of the hepatic veins for sugar — Does the liver contain sugar during life ? — Characteristics of liver-sugar — Mechanism of the production of sugar by the liver — Glyco- genic matter — Process for the extraction of glycogenic matter — Variations in the glycogenic function — Production of sugar in foetal life — Influence of digestion and of different kinds of food on glycogenesis — Influence of the nervous system, etc., on glycogenesis — Artificial diabetes — Influence of the inhalation of anaesthetics and irritating vapors on glycogenesis — Destina- tion of sugar — Alleged production of fat by the liver — Changes in the albuminoid and the corpuscular elements of the blood in their passage through the liver, 295 CHAPTER XL THE DUCTLE8S GLANDS. Probable office of the ductless glands — Anatomy of the spleen — Fibrous struc- ture of the spleen (trabeculse) — Malpighian bodies — Spleen-pulp — Vessels and nerves of the spleen — Some points in the chemical constitution of the CONTENTS. 11 spleen — State of our knowledge concerning the functions of the spleen — Variations in the volume of the spleen during life — Extirpation of the spleen — Anatomy of the suprarenal capsules — Cortical substance — Medul- lary substance — Vessels and nerves — Chemical reactions of the suprarenal capsules — State of our knowledge concerning the functions of the supra- renal capsules — Extirpation of the suprarenal capsules — Addison's disease — Anatomy of the thyroid gland — State of our knowledge concerning the functions of the thyroid gland — Anatomy of the thymus — Pituitary body and pineal gland, .... .... Page 331 CHAPTER XII. NUTRITION. Nature of the forces involved in nutrition — Protoplasm — Definition of vital properties — Life, as represented in development and nutrition — Principles which pass through the organism — Principles consumed in the organism — Xitrogenized principles — Development of power and endurance by exercise (Training) — Xon-nitrogenized principles — Formation and deposition of fat — Conditions under which fat exists in the organism — Physiological anatomy of adipose tissue — Conditions which influence nutrition — Products of dis- assimilation, 366 CHAPTER XIII. ANIMAL HEAT. General considerations — Limits of variation in the normal temperature in man —Variations with external temperature — Variations in different parts of the body — Variations at different periods of life — Diurnal variations — Rela- tions of animal heat to digestion — Influence of defective nutrition and in- anition— Influence of exercise, mental exertion, and the nervous system, upon the heat of the body, 394 CHAPTER XIV. SOURCES OF ANIMAL HEAT. Connection of the production of heat with nutrition — Seat of the production of animal heat — Relations of animal heat to the different processes of nutri- tion— Relations of animal heat to respiration — The consumption of oxygen and the production of carbonic acid in connection with the evolution of heat — Exaggeration of the animal temperature in particular parts after division of the sympathetic nerve and in inflammation — Intimate nature of the calorific processes — Equalization of the annual temperature, . 418 12 CONTENTS. CHAPTER XY. MOVEMENTS — GENEBAL PEOPEETIES OF CONTKACTILE TISSUES. Amorphous contractile substance — Ciliary movements — Movements due to elas- ticity— Varieties of elastic tissue — Muscular movements — Physiological anatomy of the involuntary muscles — Mode of contraction of the involun- tary muscular tissue — Physiological anatomy of the voluntary muscles — Primitive fasciculi — Sarcolemma — Fibrillse — Fibrous and adipose tissue in the voluntary muscles — Connective tissue — Blood-vessels and lymphatics of the muscular tissue — Connection of the muscles with the tendons — Chemical composition of the muscles — Physiological properties of the mus- cles— Elasticity — Muscular tonicity — Sensibility of the muscles — Muscular contractility, or irritability, Page 436 CHAPTER XYI. MUSCTJLAE CONTRACTION — PASSIVE OKGANS OF LOCOMOTION. Changes in the form of the muscular fibres during contraction — Secousse, Zuckung, or spasm — Spasm produced by artificial excitation — Mechanism of prolonged muscular contraction — Tetanus — Electric phenomena in the muscles — Muscular effort — Passive organs of locomotion — Physiological anatomy of the bones — Fundamental substance — Haversian rods — Haver- sian canals — Lacunae — Canaliculi — Bone-cells, or corpuscles — Marrow of the bones — Medullocells — Myeloplaxes — Periosteum — Physiological anat- omy of cartilage — Cartilage-cavities — Cartilage-cells — Fibro-cartilage, 468 CHAPTER XVII. VOICE AND SPEECH. Sketch of the physiological anatomy of the vocal organs — Vocal chords — Mus- cles of the larynx — Crico-thyroid muscles — Arytenoid muscle — Lateral cricc-arytenoid muscles — Thyro-arytenoid muscles — Mechanism of the pro- duction of the voice — Appearance of the glottis during ordinary respira- tion— Movements of the glottis during phonation — Variations in the quah'ty of the voice, depending upon differences in the size and form of the larynx and the vocal chords — Action of the intrinsic muscles of the larynx in phonation — Action of the accessory vocal organs — Mechanism of the dif- ferent vocal registers — Mechanism of speech, 490 PHYSIOLOGY OF MAN, CHAPTER I. SECRETION IX GENERAL. General considerations — Relations of the secretions to nutrition — General mechanism of secretion — Differences between the secretions and fluids containing formed anatomical elements — Division of secretions — Mechan- ism of the production of the true secretions — Mechanism of the production of the excretions — Influence of the composition and pressure of the blood upon secretion — Influence of the nervous system on secretion — Excito- secretory system of nerves — General structure of secreting organs — Ana- tomical classification of glandular organs — Secreting membranes — Fol- licular glands — Racemose glands — Tubular glands — Ductless, or blood- glands — Classification of the secreted fluids — Secretions proper (perma- nent fluids; transitory fluids) — Excretions — Fluids containing formed anatomical elements. THE phenomena classed by physiologists under the head of secretion are intimately connected with the gen- eral process of nutrition. In the sense in which the term secretion is usually received, it embraces most of the pro- cesses in which there is a separation of material from the blood or a formation of a new fluid out of matters fur- nished by the blood. The blood itself, with the lymph and the chyle, are no longer regarded as secretions. These fluids, like the tissues, are permanent constituents of the organism, undergoing those changes only that are neces- sary to their proper regeneration. They are likewise char- acterized by the presence of certain formed anatomical ele- 14 SECRETION. ments, which themselves undergo the processes of molecular destruction and regeneration. These characters are not pos- sessed by the secretions. As a rule, the latter are homoge- neous fluids, without formed anatomical elements, except as accidental constituents; such as the desquamated epithe- lium in mucous or sebaceous matter. The secretions are not permanent, self-regenerating fluids, except when they per- form simply a mechanical function, as the humors of the eye, or the liquids in serous and synovial cavities. They are either discharged from the body, when they are called excretions, or, after having performed their proper function as secretions, are taken up again in a more or less modified form by the blood. With the exception of those fluids which have a function almost entirely mechanical, the relations of the secretions to nutrition are so close, that the production of many of them forms almost a part of this great function. It is impossible, for example, to conceive of nutrition without the formation of the characteristic constituents of the urine, the bile, and the perspiration ; and it is impossible, indeed, to study satis- factorily the phenomena of nutrition without considering fully the various excrementitious principles, such as urea, cholesterine, creatine, creatinine, etc. ; for the constant forma- tion and discharge of these principles by disassimilation create the necessity for the deposition of new matter in nutrition. Again, the most important of the secretions, as contradistinguished from the excretions, are concerned in the preparation of food by digestion, for the regeneration of the great nutritive fluid. As would naturally be supposed, the general mechanism of secretion was very imperfectly understood early in the history of physiology, when little was known of the circula- tion, the functions of the digestive fluids, and particularly of nutrition. From its etymology, the term should signify separation ; but it is now known that many of the secreted fluids are formed in the glands, and are not simply sepa- DIVISION OF SECRETIONS. 15 rated, or filtered from the blood. Physiologists now regard secretion as the act by which fluids, holding certain solid principles in solution, and sometimes containing liquid nitro- genized principles, but not necessarily possessing formed anatomical elements, are separated from the blood, or are manufactured by special organs out of materials furnished by the blood. These organs may be membranes, follicles, or collections of follicles or tubes, when they are called glands. The liquids thus formed are called secretions; and they may be destined to perform some function con- nected with nutrition, or may be simply discharged from the organism. It is not strictly correct to speak of formed anatomical elements as the results of secretion, except, perhaps, in the case of the fatty particles in the milk. The leucocytes found in pus, the spermatozoids of the seminal fluid, and the ovum, which are sometimes spoken of as products of secretion, are real anatomical elements developed in the way in which these structures are ordinarily formed. It has been conclusively demonstrated, for example, that leucocytes, or pus-corpuscles, are developed in a clear blastema, without the intervention of any special secreting organ ; l and that spermatozoids and ova are generated by a true development in the testicles and the ovaries, by a process entirely differ- ent from ordinary secretion. It is important to recognize these facts in studying the mechanism by which the secre- tions are produced. It is true that in some of the secretions, as the sebaceous matter, a certain quantity of epithelium, more or less disintegrated, is found, but this is to be regarded as an accidental admixture of desquamated matter, and not as a product of secretion. Division of Secretions. — The secretions are capable of a physiological division, dependent upon differences in their functions and the mechanism of their production. Investi 1 See vol. i., Blood, p. 124, and voL ii., Absorption, p. 523. 16 SECRETION. gations within the past few years have shown that these differences are very distinct. Certain of the fluids are formed by special organs, and have important functions to perform, which do not involve their discharge from the organism. These may be classed as the true secretions ; and the most striking examples of them are the digestive fluids. Each one of these fluids is formed by a special gland or set of glands, which generally has no other function ; and they are never produced by any other part. It is the gland which produces the characteris- tic element or elements of the true secretions out of materials furnished by the blood ; and the principles thus formed never preexist in the circulating fluid. The function which these fluids have to perform is generally intermittent ; and when this is the case, the flow of the secretion is intermittent, tak- ing place only when its action is required. "When the parts which produce one of the true secretions are destroyed, as may be sometimes done in experiments upon living animals, the characteristic elements of this particular secretion never accumulate in the blood, nor are they formed vicariously by other organs. The simple effect of such an experiment is absence of the secretion, and the disturbances consequent upon the loss of its function. Certain other of the fluids are composed of water, holding one or more characteristic principles in solution, which re- sult from the physiological waste of the tissues. These prin- ciples have no function to perform in the animal economy, and are simply separated from the blood to be discharged from the body. These may be classed as excretions ; the urine being the type of fluids of this kind. The characteristic principles of the excrementitious fluids are formed in the tis- sues, as one of the results of the constant nutritive changes going on in all organized living structures. They are not pro- duced in the glands by which they are eliminated, but ap- pear in the secretion as the result of a sort of elective filtra- tion from the blood. They always preexist in the circulating DIVISION OF SECRETIONS. IT fluid, and may be eliminated, either constantly or occasion- all v, by a number of organs. As they are produced con- tinually in the substance of the tissues and taken up by the blood, they are constantly discharged into the substance of the proper eliminating organs. "When the glands which thus eliminate these principles are destroyed, or their func- tion seriously impaired, the excrementitious matters may accumulate in the blood, and give rise to certain toxic phenomena. These effects, however, are often retarded by the vicarious discharge of such principles by other organs. There are some fluids, as the bile, which perform impor- tant functions as secretions, and which nevertheless contain certain excrementitious matters. In these instances it is only the excrementitious matters that are discharged from the organism. In the serous sacs, the sheaths of tendons and of muscles, the substance of muscles, and some other situations, are found fluids which simply moisten the parts, and which contain very little organic matter and but a small proportion of in- organic salts. Although these are frequently spoken of as secretions, they are produced generally by a simple mechan- ical transudation of certain of the constituents of the blood through the walls of the blood-vessels.1 Still, it is difficult to draw a line rigorously between transudation and some of the phenomena of secretion ; particularly as late experiments upon dialysis have shown that simple osmotic membranes are capable of separating complex solutions, allowing certain con- stituents to pass much more freely than others.3 This fact ex- plains why the transuded fluids do not contain all the soluble principles of the blood in the proportions which exist in the plasma. All the secreted fluids, both the true secretions and the excretions, contain many of the inorganic salts of the blood-plasma. 1 See vol. ii., Absorption, p. 505. 8 Ibid., p. 477. 18 SECRETION. Mechanism of the Production of the true Secretions. — Although the characteristic elements of the true secretions are not to be found in the blood or in any other of the animal fluids, they can generally be extracted in quantity from the glands, particularly during their intervals of repose. This fact has been repeatedly demonstrated with regard to many of the digestive fluids, as the saliva, the gastric juice, and the pancreatic juice ; and artificial fluids, possessing many of the physiological properties of the natural secre- tions, have been prepared by simply infusing the glandular tissue in water. There can be no doubt, therefore, that even during the periods when the secretions are not discharged, the glands are taking from the blood matters which are to be transformed into principles characteristic of the individual secretions, and that this process is constant. Extending our inquiries into the nature of the process by which these pecu- liar principles are formed, it is found to bear a close resem- blance to the general act of nutrition. There are certain anatomical elements in the glands which have the power of selecting the proper material from the blood and causing them to undergo a catalytic transformation ; as the muscu- lar tissue takes from the great nutritive fluid the albumen, fibrin, etc., and transforms them into its own substance. The exact nature of this property is unexplained ; it belongs to the class of phenomena observed in living structures only, and is sometimes called vital. In all of the secreting organs a variety of epithelium is found, called glandular, which seems to possess the power of forming the peculiar elements of the different secretions. Inasmuch as the epithelial cells lining the tubes or follicles of the glands constitute the only peculiar structures of these parts, the rest being made up of basement-membrane, con- nective tissue, blood-vessels, nerves, and other structures which are distributed generally in the economy, we should expect that these alone would contain the elements of the secretions. In all probability this is the fact ; and with re- MECHANISM OF SECRETION. 19 gard to some of the glands, this has been satisfactorily de- monstrated. It has been found, for example, that the liver- cells contain the glycogenic matter formed by the liver ; 1 and it has been further shown that when the cellular structures of the pancreas have been destroyed, the secretion is no longer produced.2 There can be hardly any doubt with re- gard to the application of this principle to the glands gener- ally, both secretory and excretory. Indeed, it is well known to pathologists, that when the tubes of the kidney have be- come denuded of their epithelium, they are no longer capable of separating from the blood the peculiar constituents of the urine. "With regard to the origin of the principles peculiar to the true secretions, it is impossible to entertain any other view than that they are produced in the epithelial structures of the glands ; and the old idea that they exist ready-formed in the blood, though adopted by some physiologists of the present day,8 cannot be maintained. While the secretions contain inorganic salts transuded in solution from the blood, the organic constituents, such as pepsin, ptyaline, pancrea- tine, etc., are readily distinguished from all other albuminoid principles by their peculiar physiological properties ; al- though some of them are apparently identical with albumen in their ultimate composition and in most of their chemical reactions. It may be stated, then, as a general proposition, that the characteristic elements of the true secretions, as contradistin- guished from the excretions, are formed de novo by the epi- thelial structures of the glands, out of material furnished by the blood ; and that their formation is by no means confined to what is usually termed the period of functional activity of the glands, or the time when the secretions are poured out, 1 SCHIFF, De la nature des granulations qui remplissent les cellules hepatiques : Amidon animale. — Comptes rendus, Paris, 1859, tome xlviii., p. 880. 2 BERNARD, Memoire sur le pancreas, Paris, 1856, pp. 17 and 69. 3 MILNE-EDWARDS, Lecons sur la physiologie^ Paris, 1862, tome vii., p. 282. 20 SECRETION. but takes place more or less constantly when no fluid is dis- charged. It is more than probable that the formation of the ele- ments of the secretions takes place with fully as much activ- ity in the intervals of secretion as during the discharge of fluid ; and most of the glands connected with the digestive system seem to require certain intervals of repose, and are capable of discharging their secretions for a limited time only. When a secreting organ is called into functional activity — like the gastric mucous membrane, or the pancreas, upon the introduction of food into the alimentary canal — a marked change takes place. The circulation in the part is then very much increased in activity ; thus furnishing the water and the inorganic elements of the secretion. This difference in the vascularity of the glands during their activity is very marked when the organs are exposed in a living animal, and is one of the important facts bearing upon the mechanism of secretion. Beaumont observed this in his experiments on St. Martin, and was the first to show conclusively that the gastric juice is secreted only when food is taken into the stomach, or some stimulation is applied to its mucous mem- brane.1 Bernard, in his experiments on the pancreas, noted the pale appearance of the gland during the intervals of digestion, and its reddened and congested condition when the secretion flowed from the duct ; a and these observations have been confirmed by all who have experimented upon the glands in living animals. In later experiments upon the circulation in the salivary glands and its relation to secretion, Bernard has investigated this subject fully, with the most definite and satisfactory re- sults.3 His observations were made chiefly on the submaxil- 1 BEAUMONT, Experiments and Observations on the Gastric Juice, and the Physiology of Digestion, Plattsburg, 1833, p. 103. 2 BERNARD, Memoire sur le pancreas, Paris, 1856, p. 43. 3 BERNARD, Lecons sur les proprietes physiologiques et les alterations patho- MECHANISM OF SECRETION. 21 lary gland in dogs ; and lie has shown that during the func- tional activity of this organ, if a tube be introduced into the vein, the quantity of blood which may be collected in a given time is four or five times that which is discharged in the in- tervals of secretion.1 It was ascertained, also, that the venous blood coming from the gland contained much less water than the arterial blood ; and on comparing the quantity of water lost by the blood in its passage through the gland in a gh»en time with the quantity discharged in the saliva, they were found to exactly correspond.11 The differences in the quantity and the composition of the blood coming from the glands during their repose and their activity have an important bearing upon the mechan- ism of secretion. As far as the composition is concerned, these differences appear to be mainly dependent upon the modifications in the circulation. When the gland is in re- pose, the blood coming from it has the usual dark, venous hue and contains the ordinary proportion of carbonic acid ; but during secretion, when the quantity of blood passing through the organ is increased, the color is nearly as bright as that of arterial blood, and the proportion of carbonic acid is very small. At this time, also, the blood is frequently discharged from the vein pulsatim to the distance of several inches.3 The cause of this difference in color is very easily understood. During the intervals of secretion, the blood is sent to the gland for the purposes of nutrition and the man- ufacture of the elements of the secretion. It then passes logiques des liquides de Vorganisme, Paris, 1859, tome ii., p. 272, et seq. ; Du role des actions reflexes paralysantes dans le phenomene des secretions.— Journal de Vanatomie et de la physiologie, Paris, 1864, tome i., p. 507, et seq. ; Lecons sur les proprietes des tissus vivants, Paris, 1866, p. 400, et seq. 1 Unpublished lectures delivered by Bernard at the College of France in the summer of 1861. 2 Unpublished lectures, 1861 ; Journal at tanatomie et de la physiologic, Paris, 1864, tome i., p. 513 ; and Lemons sur Ifs proprietes des tissits vivants, Paris, 1866, p. 401. 3 BERNARD, Liquides de Vorganisme, Paris, 1859, tome ii., p. 296. 22 SECRETION. through the part in moderate quantity and undergoes the usu- al change from arterial to venous, in which a great part of the oxygen disappears and carbonic acid is formed ; but, when secretion commences, the ordinary nutritive changes are not sufficient to deoxidize the increased quantity of blood, and the venous character of the blood coming from the part is very much less marked.1 These facts enable us to form a pretty clear idea of the mechanism of secretion; though the exact nature of the forces which effect the changes of the organic princi- ples of the blood into the characteristic elements of the secretions is not understood. Experiments, however, have shown that in the act of secretion there are two tolerably distinct processes : 1. It may be assumed that at all times the peculiar se- creting cells of the glands are forming, more or less actively, the elements of the secretions, which may be washed out of the part or extracted by maceration ; but during the inter- vals of secretion, the quantity of blood received by the glands is relatively small. 2. In obedience to the proper stimulus, when a gland takes on secretion, the quantity of blood which it receives is four or five times greater than it is during repose. At that time, water, with certain of the salts of the blood in solution, passes into the secreting structure, takes up the characteristic elements of the secretion, and fluid is dis- charged by the duct. In all the secretions proper, there are intervals, either of complete repose, as is the case with the gastric juice or the pancreatic juice, or periods when the activity of the secretion is very greatly diminished, as in the saliva. These periods of repose seem to be necessary to the proper performance of the function of the secreting glands ; forming a marked con- trast with the constant action of the organs of excretion. It 1 This subject is more fully discussed in vol. i., Blood, p. 106, under the head of " Color of the Blood." MECHANISM OF SECRETION. 23 is well known, for example, that the function of digestion is seriously disturbed when the act is too prolonged, from the habitual ingestion of an excessive quantity of food. With regard to the pancreas this fact has been demonstrated in the most satisfactory manner. The experiments of Bernard and others have shown that this organ is peculiarly suscep- tible to irritation ; and when a tube is fixed in its duct, after a time the flow of the secretion may become constant, leav- ing no intervals for repose of the gland. "WTien this occurs, the fluid discharged loses the character of the normal secre- tion and is found to possess none of its peculiar diges- tive properties.1 In one or two instances in which the irrita- tion of the tube introduced into the pancreatic duct did not produce a constant secretion, the fluid, which was discharged intermittently in the normal way, possessed all its physio- logical properties.2 From the considerations already mentioned, it is evident that the secretions, as the rule, are formed by the epithelial structures of the glands. There has been a great deal of speculation with regard to the mechanism of this action of the cells. As we before remarked, this question cannot be con- sidered as settled. It does not seem probable that the cells are ruptured during secretion and discharge their contents into the ducts, for under these circumstances we should expect to find some of their structure in the secreted fluid ; whereas, aside from accidental constituents, the secretions are homogeneous, and do not contain any formed anatomical elements. There is no good reason for supposing that this action takes place, and that more or less of the glandular epithelium is destroyed whenever secretion occurs ; and, in the present state of our knowledge, we can only assume that the secreting cells induce catalytic transformations in the organic elements of the blood and modify transudation, with- out pretending to understand the exact nature of this process. 1 See vol. ii., Digestion, p. 337. 2 BERNARD, Memoire sur le pancreas, Paris, 1856, p. 46. 24: SECRETION. The theory that the discharge of the secretions is due simply to mechanical causes, and is attributable solely to the increase in the pressure of blood, cannot be sustained. Pressure undoubtedly has considerable influence upon the activity of secretion ; but the flow will not always take place in obedience to simple pressure, and secretion may be in- duced for a limited time without any increase in the quan- tity of blood circulating in the gland. In the numerous ex- periments by Bernard upon the influence of the circulation upon secretion in the submaxillary gland of the dog, these facts are very clearly shown. By very powerful galvaniza- tion of what he termed the motor nerve of the gland (the chorda tympani), secretion was excited, but the circulation was reduced ; and again, after ligation of the vein, by which the gland was engorged with blood and the circulation could not be modified, galvanization of the nerve was nevertheless followed by an increase in the secretion. A slight secretion was also produced by galvanization of the nerve after the artery supplying the gland had been tied. These experi- ments are made with great facility upon the submaxillary gland of the dog, for the reason that the parts may be ex- posed and operated upon without interrupting the secretory function, and the nerves and vessels communicating with the gland can be easily isolated. The function of most of the glands, however, becomes so much disturbed by exposure, that the influence of the nerves upon their action is observed with great difficulty. From the experiments just cited, Bernard concludes that the glands possess a peculiar irritability, which is manifested by their action in response to proper stimulation. During their secretion, they generally receive an increased quantity of blood ; but this is not indispensable, and secretion may be excited without any modification of the circulation. This irritability will disappear when the artery supplying the part with blood is ligated for a number of hours ; and secretion cannot then be excited, even when the motor nerve is stimu- MECHANISM OF EXCKETIOX. ZO lated and the blood is again allowed to circulate. If the gland be not deprived of blood too long, the irritability is soon re- stored ; but it may be permanently destroyed by depriving the part of blood for a long time.1 These observations are very striking, and show a certain similarity between glandular and muscular irritability, though their properties are mani- fested in very different ways. Mechanism of the Production of the Excretions. — Certain of the glands have the function of separating from, the blood excrementitious matters, which are of no use in the economy, and are simply to be discharged from the system. These matters, which will be fully considered, both in connection with the fluids of which they form a part, and under the head of nutrition, are entirely different in their mode of pro- duction from the characteristic elements of the secretions. Our definite information concerning the mechanism of ex- cretion dates from the researches of Prevost and Dumas, who discovered urea in the blood of dogs after its elimination had been arrested by extirpation of the kidneys.2 These experi- ments were confirmed by Segalas and Yauquelin ; 3 but at that time the means of analysis of the animal fluids were not sufficiently delicate to enable chemists to detect urea in healthy blood. The later observations of Marchand, how- ever, demonstrated its constant presence in very small quantity in the blood.* These analyses have been repeated- ly confirmed, and it is now generally believed that all the excrementitious principles exist in greater or less quantity 1 Unpublished lectures delivered by Bernard at the College of France in the summer of 1861. 2 PREVOST ET DUMAS, Examin du sang et de son action dans les divers plie- nomenes de la vie.—Annales de ckimie et de physique, Paris, 1821, tome xviii., p. 280. 3 SEGALAS, Sur des nouvelles experiences relatives aux propriete* medicamen- teuscs de Turce, etc. — Journal de physiologic, Paris, 1822, tome ii., p. 354. 4 MARCHAND, Sur la presence de Turee dans le sang. — Annales des sciences naturelles, Paris, 1838, 2me serie, tome x., p. 46. 26 SECEETION. in the circulating fluid.1 That urea is actually separated from the blood by the kidneys is further confirmed by recent observations, showing that in the renal artery the proportion of this principle is about twice as great as in the renal vein.3 Adopting this view, we have nothing to do at present with the formation of excrementitious principles. This takes place in the tissues and is connected with the general process of nutrition ; and in the excreting glands there is simply a separation of matters already formed. The action of the ex- creting organs being constant, there is not that regular peri- odic increase in the activity of the circulation which is observed in secreting organs ; but it has been observed that the blood that comes from the kidneys is nearly as red as arterial blood, showing that the quantity of blood which this organ receives is greater than is required for mere nutrition, the excess, as in the secreting organs, furnishing the water and inorganic salts that are found in the urine. It has also been shown that when the secretion of urine is interrupted, the blood of the renal veins becomes dark like the blood in the general venous system.3 The function of excretion is not, under all conditions, confined to the ordinary excretory organs. When their func- tion is disturbed, certain of the secreting glands, as the folli- cles of the stomach and intestine, may for a time eliminate excrementitious matters ; but this action is abnormal, and is 1 In a recent work on the urine (ROBERTS, A Practical Treatise on Urinary and Renal Diseases, Philadelphia, 1866, p. 359), it is stated on the authority of observations and analyses by Oppler, Schottin, Perls, and Zalesky, that urea and uric acid are actually produced in the kidneys. These statements, which will be discussed more fully hereafter, are in direct opposition to facts that have been regarded as settled by accurate analyses of the blood, and cannot be accepted without confirmation. It is supposed, however, that urea and the urates are the result of transformation of other excrementitious principles existing in the blood, and are not formed de novo, like the elements of the true secretions. 2 ROBIN, Lecons sur les humeurs normales et morbides dw corps de rhomme^ Paris, 1867, p. 89. 3 BERNARD, Liquides de Torganisme, Paris, 1859, tome i., pp. 257 and 297. MODIFICATIONS OF SECRETION. 27 analogous to the elimination of foreign matters from the blood by the glands. Influence of the Composition and Pressure of the Blood upon Secretion. — Under normal conditions the composition of the blood has little to do with the action of the secreting organs, as it simply furnishes the material out of which the characteristic principles of the secretion are formed ; ' but when certain foreign matters are taken into the system or are injected into the blood-vessels, they are eliminated by the different glands, both secretory and excretory. These organs seem to possess a power of selection in the elimination of different substances. Thus, sugar, ferrocyanide of potas- sium, and the salts of iron, are eliminated in greatest quantity by the kidneys ; the salts of iron by the kidneys and the gastric tubules ; and iodine by the salivary glands. The act of secretion is almost always accompanied with increase in the pressure of blood in the vessels supplying the glands ; and it has been shown, on the other hand, that an exaggeration in the pressure, if the nerves of the glands do not exert an opposing influence, increases the activity of se- cretion. The experiments of Bernard on this point show the influence of pressure on the salivary and the renal secretion, particularly the latter. After inserting a tube into one of the ureters of a living animal, so that the activity of the renal secretion could be accurately observed, the pressure in the renal artery was increased by tying the crural and the brachial. It was then found that the flow of urine was markedly increased. The pressure was afterward dimin- ished by the abstraction of blood, which was followed by a corresponding diminution in the quantity of urine.1 The same phenomena were observed in analogous experiments on the submaxillary secretion. These striking facts, as we have already seen, do not de- monstrate that secretion is due simply to an increase in the 1 BERNARD, Liquids de rorganisme, Paris, 1859, tome ii., p. 155, et seq. 250 SECRETION. pressure of blood in the glands, though this undoubtedly exerts an important influence. It is necessary that every condition should be favorable to the act of secretion, for this influence to be effective. Experiments have shown that pain is capable of completely arresting the secretion of urine ; operating undoubtedly through the nervous system. If, now, the flow of urine be arrested by pain, an increase in the pressure of blood in the part fails to influence the secretion. To illustrate this fact more fully, Bernard divided the nerves on one side, through which the reflex nervous action was communicated to the kidney, leaving the other side intact. He then found that increase in the arterial pressure, accom- panied with pain, diminished the flow of urine on the sound side, through which the nervous action could operate, and increased it upon the other.1 We have already alluded to the experiments in which secretion was excited through the nervous system, when the arterial pressure had been con- siderably diminished. The influence of pressure of blood upon secretion may, then, be summed up in a few words : There is always an in- crease in the activity of secretion when the pressure of blood in the glands is increased, and a diminution when the pres- sure is reduced ; except when there is some modifying influ- ence operating through the nervous system. Influence of the Nervous System on Secretion. — The fact that the secretions are generally intermittent in their flow, being discharged in obedience to impressions which are made only when there is a demand for the exercise of their func- tions, would naturally lead to the supposition that they are regulated, to a great extent, through the nervous system ; particularly as it is now well established that the nerves are capable of modifying and regulating local circulations. The same facts apply, to a certain extent, to the excretions, which 1 These experiments were detailed by Bernard in his lectures at the College of France in the summer of 1861. MODIFICATIONS OF SECRETION. 29 are also subject to considerable modifications. A few years ago, indeed, there was considerable discussion regarding a subdivision of the reflex system of nerves, which was supposed to preside over secretion, and was called the excito-secretory system. The facts which led to the description of this sys- tem of nerves had long been observed ; and they simply il- lustrated the production of secretion in response to irritation. Dr. H. F. Campbell, of Augusta, Georgia, published, in 185T, an essay on the excito-secretory system of nerves, which received the prize of the American Medical Associa- tion for that year ; 1 and a few months later, the same idea was put into shape by Dr. Marshall Hall, who, however, yield- ed the priority to Dr. Campbell. To Dr. Campbell certainly belongs the credit of proposing the theory that the sympa- thetic system presides over secretion ; but in this he only rea- soned from the old experiments of Pourfour du Petit and others, and failed to give any satisfactory physiological de- monstration of his views. In 1852, five years before the publication of Dr. Camp- bell's essay, in the course of his researches on the secretions of the different salivary glands, Bernard pointed out the reflex character of the act of secretion, and demonstrated experimentally the influence of certain nerves upon the dis- charge of fluid from the duct of the submaxillary. These experiments were the first to give a clear idea of the action of the nervous system upon secretion, and they have been 1 CAMPBELL, Essays on the Secretory and the Excito-secretory System of Nerves in their ^Relations to Physiology and Pathology, Philadelphia, 1857 ; also, Trans- actions of the American Medical Association for 1857. In 1850, Dr. Campbell published in the Southern Medical and Surgical Jour- nal an Essay on the Influence of Dentition in producing Disease ; in which he re- marked the fact, that during dentition, the irritation in the mouth frequently in- duced, in addition to the usual increase hi the salivary secretions, an increased action of the kidneys and the mucous membrane of the intestinal canal. He states that " this increase and change in the secretion are effected by the agency of the altered function of the nerve upon the arteries from which these secre- tions are eliminated." Dr. Campbell supposed that the nerves through which these operations took place belonged to the sympathetic system. 30 SECRETION. confirmed and extended by the subsequent observations of Bernard and other physiologists. The following are the most important facts, taken from Bernard, bearing upon the question under consideration : l " Introducing into the mouth of a dog, in which the three salivary ducts have been isolated, a very sapid substance, such as vinegar, for example, it is found that the duct of the submaxillary discharges saliva in very great abundance. But, by operating directly upon the nerve of taste itself, I have been enabled to act solely upon the special secretion, and to demonstrate directly this intimate relation between the secretion of the submaxillary saliva and the sense of gus- tation. " When we divide in a dog the lingual nerve opposite the middle of the horizontal process of the lower jaw, and pinch the central end, which is connected with the encephalon, we immediately see the duct of the submaxillary excrete saliva with great activity, while the ducts of the parotid and sub- lingual, which are not connected with the sense of gustation, remain perfectly dry. This sort of functional reaction, which irritation of the central end determines exclusively, in the submaxillary gland, is explained, for in operating thus we produce in the nervous centre the impression of exaggerated gustatory sensation, which immediately provokes, by an ac- tion called reflex !, the salivary secretion destined physiologi- cally to allay and diminish the too acute impression of sapid substances." These experiments clearly demonstrated the importance of the nervous influence in the production of the secretions ; but the more recent observations of Bernard show that the effects are produced mainly by increasing the activity of the circulation in the glands. This takes place in greatest part through filaments from the sympathetic system, which are 1 BERNARD, Recherches cTanatomie et de physiologie comparee sur ies ylandes soli- vaircs chez Thomme et Ies animaux vertebres. — Comptes rendus, Paris, 1852, tome xxxiv., p. 239. MODIFICATIONS OF SECRETION. 31 distributed to the muscular coats of the arteries of supply. When these filaments are divided, the circulation is increased here, as in other situations, and secretion is the result ; and, if the extremity of the nerve connected with the gland be galvanized, contraction of the vessels follows, and the secre- tion is arrested.1 With regard to many of the glands, Bernard has shown that the influence of the sympathetic is antagonized by nerves derived from the cerebro-spinal system, which he calls the motor nerves of the glands. The motor nerve of the sub- maxillary is the chorda tympani ; and as both this nerve and the sympathetic, together with the excretory duct of the gland, can be easily exposed and operated upon in a living animal, most of the experiments of Bernard have been per- formed upon this gland. When all these parts are exposed and a tube introduced into the salivary duct, division of the sympathetic induces secretion, with an increase in the circu- lation in the gland, the blood in the vein becoming red. On the other hand, division of the chorda tympani, the sympa- thetic being intact, arrests secretion, and the venous blood coming from the gland becomes dark. If the nerves be now galvanized alternately, it will be found that galvanization of the sympathetic produces contraction of the vessels of the gland and arrests secretion, while the stimulus applied to the chorda tympani increases the circulation and excites se- cretion.3 These experiments show that the submaxillary gland has distributed to it a special nerve which is capable of exciting its functional activity, the sympathetic ramifying upon the walls of the blood-vessels in this, as in other situa- tions ; and it remains to see whether other glands are like- wise supplied with motor nerves. In his lectures, delivered in 1861, Bernard announced that he had demonstrated the existence of such nerves for the other salivary glands. 1 BERNARD, Liquides de Vorganisme, Paris, 1859, tome ii., p. 270. 8 Op. cit., p. 267, et seq. 32 SECEETION. The motor nerve of the parotid is derived from the auri- culo-temporal branch of the submaxillary division of the fifth pair ; and the nerve of the sublingual, from the lingual branch of the fifth. He found, however, that neither the. parotid nor the sublingual was so easily ex- cited to secretion by galvanization of the nerves as the submaxillary. With regard to other glands, the condi- tions for experimentation are so difficult, and some of them, as the pancreas, are so sensitive to irritation, that it is impos- sible to repeat on them the experiments made upon the sali- vary glands. Enough is known, however, of the nervous influences which modify secretion, to admit of the inference that all the glands are possessed of nerves through which reflex phenomena, affecting their secretions, take place. It is the motor, or functional nerve of the gland through which the reflex action takes place ; the influence of the sympa- thetic being constant, and the same as in other parts where it is distributed to blood-vessels. As reflex phenomena involve the action of a nervous centre, it becomes an interesting question to determine whether any particular parts of the central nervous system preside over the various secretions. ' We must refer again to the experiments of Bernard for an elucidation of this ques- tion. If a puncture be made in the space included between the origin of the pneumogastrics and the auditory nerves in the floor of the fourth ventricle, there is an increase in the discharge of urine, and an excretion of sugar, from an ex- aggeration in the sugar-producing function of the liver. Irritation applied a little higher, toward the pons varolii, just posterior to the origin of the fifth pair of nerves, is followed by a great increase in the activity of the salivary secretion.1 1 BERNARD, Lemons sur la physiologic et la pathologic du systeme nervcux, Paris, 1858, tome i., pp. 898-399. This operation is easily performed upon the rabbit, by passing an instrument directly through the occipital bone, entering just behind the protuberance, and through the cerebellum to the medulla oblongata. These experiments will be more fully described in connection with the nervous system. STRUCTURE OF SECRETING ORGANS. 33 Mental emotions, pain, and various circumstances, the influence of which upon secretion has long been observed, operate through the nervous system. Numerous familiar instances of this kind are quoted in works on physiology : such as the secretion of tears ; arrest or production of the sali- vary secretions ; sudden arrest of the secretion of the mam- mary glands, from violent emotion ; increase in the secretion of the kidneys or of the intestinal tract, from fear or anxiety ; with other examples which it is unnecessary to ennumerate. The effects, upon some of the secretory organs, of de- struction of the nerves distributed to their parenchyma are very curious and interesting. Miiller and Peipers destroyed the nerves distributed to the kidney, and found that not only was the secretion arrested in the great ma- jority of instances, but that the tissue of the kidneys be- came softened and broken down.1 These experiments have been lately repeated by Bernard. He found that animals operated upon in this way died, and that the tissue of the kidney was broken down into a fetid, semifluid mass. After division of the nerves of the salivary glands, the organs be- came atrophied, but did not undergo the peculiar putrefac- tive change which was observed in the kidneys. The same effect was produced when the nerve was paralyzed by in- troducing a few drops of a solution of woorara at the origin of the little artery which is distributed to the submaxillary gland.3 General Structure of Secreting Organs. — In treating of the mechanism of secretion and excretion, it has been evi- dent that all glandular organs must be supplied with blood to furnish the materials for secretion, and be provided with epithelium, which changes these matters into the characteris- tic elements of the secretions. We can understand how cer- 1 MUELLER, Manuel de physiologic, Paris, 1851, tome i.,p. 391. 8 BERNARD, Lefonssur les proprietes des tissus vivant*, Paris, 1866, p. 399. • 3 34 SECRETION. tain of tlia liquid and saline constituents of the blood can escape by exosmosis through the homogeneous walls of the capillaries,1 but the more complex fluids require for their formation a different kind of action ; although, in the act of secretion, there is considerable transudation of liquid and saline matters, which take up in their course the peculiar principles formed by the cells. Though it is somewhat difficult to draw a line between transudation and the simplest forms of secretion, it may be assumed, in general terms, that fluids which are exhaled directly from the blood-vessels, without the intervention of glandular apparatus or of a secreting membrane, are transu- dations ; while all fluids produced by simple membranes, by follicles, or discharged from the ducts of glands, are secre- tions. This division places the intermuscular fluid and the fluid found in all soft tissues among the transudations, and the serous and synovial fluids among the secretions. The serous and synovial membranes present the simplest form of a secreting apparatus. Blood is supplied to them in small quantity, and on their free surfaces are arranged one or two layers of epithelial cells which effect the slight changes that take place in the transuded fluids. In some of the serous membranes, as the pleura and peritoneum, the amount of secretion is very small, being hardly more than a vaporous exhalation ; but others, like the serous pericardium and the synovial membranes, secrete a considerable quantity of fluid. The action of all of these membranes may become exaggerated, as a pathological condition, and the amount of their secretions is then very large. Anatomists have now a pretty clear idea of the structure of what are called the glandular organs ; and it will be seen that they simply present an arrangement by which the se- creting surface is increased, and at the same time compressed, as it were, into a comparatively small space. The mucous follicles, for example, are simple inversions of a portion of 1 See vol. ii., Absorption, p. 505. CLASSIFICATION OF GLANDS. 35 the mucous membrane ; while the ordinary racemose glands are nothing more than collections of follicles around the ex- tremities of excretory ducts. These ideas concerning the general anatomy of the glands date from the observations of Malpighi,1 who was the first to correct the old notion that the secretions were discharged into the glandular organs through openings in the blood-vessels. It is evident that nothing could have been known of the mechanism of Secre- tion before the connection between the arteries and veins had been ascertained, which, it will be remembered, was also discovered by Malpighi. Although the ideas of Malpighi were not at first generally received, more recent observations with the microscope have shown that they were in the main correct ; though, from the imperfection of his optical instru- ments, Malpighi was unable to investigate the minute struc- ture of the glands very thoroughly. Anatomical Classification of Glandular Organs. — The organs which produce the different secretions are susceptible of a classification according to their anatomical peculiarities, which greatly facilitates their study. They may be divided as follows : 1. Secreting membranes. — Examples of these are the se- rous and synovial membranes. 2. Follicular glands. — Examples of these are the simple mucous follicles, the follicles of the stomach, the follicles of Lieberkiihn, and the uterine follicles. 3. Tubular glands. — Examples of these are the cerumi- nous glands, the sudoriparous glands, and the kidneys. 4. Racemose glands, simple and compound. — Examples of the simple racemose glands are the sebaceous and Meibo- mian glands, the tracheal glands, and the glands of Brunn. Examples of the compound racemose glands are the salivary 1 MALPIGHI, Exercitationes A natomicce de Structura Vlscerum. — Opera Omnia, Ludg. Batav., 1687, tomus ii., p. 257. 36 SECRETION. glands, the pancreas, the lachrymal glands, and the mam- mary glands. 5. Ductless , or Hood-glands. — Examples of these are the thymus, the thyroid, the supra-renal capsules, and the spleen. The liver is a glandular organ which cannot be placed in any one of the above subdivisions, as we shall see when we treat specially of its anatomy. The lymphatic glands and other parts connected with the lymphatic and the lacteal system are not embraced in the above classification.1 These are sometimes called conglobate glands. The general structure of secreting membranes and the follicular glands is very simple. The secreting parts consist of a membrane, generally homogeneous, on the secreting sur- face of which are found epithelial cells, either tesselated or of the variety called glandular. Beneath this mem- brane ramify the blood-vessels which furnish the elements of the secretions. The follicles are simply digital inversions of this structure, with rounded, blind extremities, the glan- dular epithelium lining the tube. The tubular glands have essentially the same structure as the follicles, except that the tubes are long and more or less convoluted. The more complex of these organs contain connective tissue, blood-vessels, nerves, and lymphatics. The compound racemose glands are composed of branch- ing ducts, around the extremities of which are arranged collections of rounded follicles, like bunches of grapes. In addition to the epithelium, basement-membrane, and blood- vessels, these organs contain connective tissue, fibro-plastic elements, lymphatics, involuntary muscular fibres, and nerves. In the simple racemose glands the excretory duct does not branch. The ductless glands contain blood-vessels, lymphatics, nerves, sometimes involuntary muscular fibres, fibro-plastic elements, and a peculiar structure called pulp, which is com- 1 For the anatomy of the lymphatic system, see vol. ii., Absorption, p. 439, et seq. CLASSIFICATION OF SECRETIONS. 37 posed of fluid with cells and occasionally closed vesicles. These are sometimes called blood-glands, because they are supposed to modify the blood as it passes through their substance. The testicles and the ovaries are not simple glandular organs; for in addition to the production of mucous or watery secretions, their principal function is to develop cer- tain anatomical elements, the spermatozoids and the ova. The physiology of these organs will be considered in connec- tion with the subject of generation. Classification of the Secreted Fluids. — The products of the various glands may be divided, according to their function, into secretions and excretions. The secreted fluids may be subdivided into the permanent secretions, which have a more or less mechanical function, and transitory secretions ; some of the latter, like mucus, are thrown off in small quantity, without being actually excrementitious ; others, like most of the digestive fluids, are produced intermittently and rapidly, and finally undergo resorption. Tabular View of the Secreted Fluids. SECRETIONS PBOPEB. Permanent Fluids. Serous fluids. Synovial fluid. Aqueous humor of the eye. Vitreous humor of the eye. Fluid of the labyrinth of the internal ear. Cephalo-rachidian, or subarachnoid fluid. Transitory Fluids. Mucus, in many varieties. Sebaceous matter. Cerumen, the waxy secretion of the external meatus. Meibomian fluid. Milk and colostrum. Tears. Saliva. 38 SECRETION. Gastric juice. Pancreatic juice. Secretion of the glands of Brunn. Secretion of the follicles of Lieberkiihn. Secretion of the follicles of the large intestine. Bile (also an excretion). EXCRETIONS. Perspiration, and the secretion of the axillary glands. Urine. Bile (also a secretion). FLUIDS CONTAINING FORMED ANATOMICAL ELEMENTS. Seminal fluid, containing, besides spermatozoids, the secretions of a number of glandular structures. Fluid of the Graafian follicles. CHAPTEK II. SEKOUS AND SYNOVIAL FLUIDS MUCUS SEBACEOUS FLUIDS. Physiological anatomy of the serous and synovial membranes — Synovial fringes — Bursse — Synovial sheaths — Pericardial, peritoneal, and pleural secre- tions— Quantity of the serous secretions — Synovial fluid — Mucus — Mucous membranes — Mucous membranes covered with pavement-epithelium — Mu- cous membranes covered with columnar epithelium — Mucous membranes covered with mixed epithelium — Mechanism of the secretion of mucus — Composition and varieties of mucus — Microscopical characters of mucus — Xasal mucus — Bronchial and pulmonary mucus — Mucus secreted by the lining membrane of the alimentary canal — Mucus of the urinary passages — Mucus of the generative passages — Conjunctival mucus — General func- tion of mucus — Xon-absorption of certain soluble substances, particularly venoms, by mucous membranes — Sebaceous fluids — Physiological anatomy of the sebaceous, ceruminous, and Meibomian glands — Ordinary sebaceous matter — Smegma of the prepuce and of the labia miuora — Yernix caseosa — Cerumen — Meibomian secretion — Function of the Meibomian secretion. Physiological Anatomy of the Serous and Synovial Membranes. THE serous and synovial membranes, which are fre- quently classed together by anatomists, present several well- marked points of distinction, both as regards their structure and the products of their secretion. The serous membranes are the arachnoid, pleura, pericardium, peritonaeum, and tunica vaginalis testis. The synovial membranes are found around all the movable articulations. They also form elon- gated sacs enveloping many of the long tendons, and exist in various parts of the body in the form of shut sacs, when they are called bursae. 40 SECRETION. Serous Membranes. — The structure of the serous mem- branes is very simple. They consist of a dense tissue of fibres, which is frequently quite closely adherent to the sub- jacent parts, and covered by a single layer of pavement, or tesselated epithelium. The fibres are mainly of the inelastic variety arranged in bundles, interlacing each other in the form of a close net-work, and mingled with small, wavy fibres of elastic tissue and numerous blood-vessels. It has not been satisfactorily demonstrated that the serous mem- branes contain nerves and lymphatics, though the latter are generally quite abundant in the subjacent parts, particularly beneath the visceral layers.1 The capillary blood-vessels are in the form of a close, polygonal net-work, with sharp angles. The epithelium of the serous membranes is pale, regular, with rather large nuclei, and is easily detached after death. Todd and Bowman describe a delicate basement -membrane between the fibrous structure and the layer of epithelium,2 but others have not been able to distinguish it, and the ex- istence of such a membrane is considered doubtful.3 These membranes, as a rule, form closed sacs, with their opposing or free surfaces nearly in apposition. The secre- tion, which is generally very small in quantity, is contained in their cavity. The exceptions to this are the arachnoid membrane, the surfaces of which are exactly in apposition, the fluid being situated beneath both layers,4 and the perito- neum of the female, which has an opening on either said for the Fallopian tubes. Synovial Membranes. — The true synovial membranes are found in the diarthrodial, or movable articulations ; but in 1 See vol. ii., Absorption, p. 433. 2 TODD AND BOWMAN, Physiological Anatomy and Physiology of Man, Lon- don, 1845, vol. i., p. 130. 3 BRINTON, Serous and Synovial Membranes. — Cyclopedia of Anatomy and Physiology, London, 1847-1849, vol. iv., part i., p. 514. * MAGENDIE, Memoire sur un liquide qui se trouve dans le crane et le canal vertebral de Vhomme et des animaux mammiferes. — Journal de physiologic, Paris, 1825, tome v., p. 36. SYNOVIA^ MEMBRANES. 41 various parts of the body are found closed sacs, sheaths, etc., which resemble synovial membranes both in structure and function. Every movable joint is enveloped in a capsule which is closely adherent to the edges of the articulating cartilage and is even reflected upon its surface for a short distance. It was formerly thought that these membranes, like the serous sacs, were closed bags, with one layer attached to the cartilage, and the other passing between the bones so as to enclose the joint; but it is now the general opinion that the cartilage which encrusts the articu- lating extremities of the bones, though bathed in synovial fluid, is not itself covered by a membrane. The fibrous portion of the synovial membranes is more dense and resisting and less elastic than the serous mem- branes. It is composed of white inelastic fibrous tissue, with a few elastic fibres and blood-vessels. The latter are generally not so numerous as in the serous membranes. The internal surface is lined with small cells of flattened, pavement-epithelium, with rather large, rounded nuclei. These cells exist in from one to two or four layers.1 In most of the joints, especially those of large size, as the knee and hip, the synovial membrane is thrown into folds which contain a considerable amount of true adipose tissue. In nearly all the joints, the membrane presents fringed, vascular processes, called sometimes synovial fringes. These are composed of looped vessels of considerable size ; and when injected they bear a certain resemblance to the choroid plexus. The edges of these fringes present numer- ous leaf-like, -membranous appendages, of a great variety of curious forms. They are generally situated near the attach- ment of the membrane to the cartilage. There is no reason for supposing that either the adipose folds or the vascular fringes have any special office in the production of the eynovial secretion, different from that of other portions of the membrane, though such a theory has been advanced. 1 KOLLIKER, Handbuch der Gewebelehre des Menschen, Leipzig. 1867, S. 201. 42 SECRETION. The arrangement of the synovial bursse is very simple. Wherever a tendon plays over a bony surface, we find a delicate membrane in the form of an irregularly shaped, closed sac, one layer of which is attached to the tendon, and the other to the bone. These sacs are lined with an epi- thelium like that found in the synovial cavities, and they secrete a true synovial fluid. Numerous bursse are also found beneath the skin, especially in parts where the integu- ment moves over bony prominences, as the olecranon, the patella, and the tuberosities of the ischium. These sacs, sometimes called bursse mucosse, are much more common in man than in the inferior animals, and have essentially the same function as the deep-seated bursse. The form of both the superficial and deep-seated bursse is very irregular, and their interior is frequently traversed by small bands of fibrous tissue. The synovial sheaths, or vaginal processes, line the canals in which the long tendons play, particularly the tendons of the flexors and extensors of the fingers and toes. They have essentially the same structure as the bursse, and present two layers, one of which lines the canal, while the other is reflected over the tendon. The vascular folds, described in connection with the articular synovial membranes, are found in many of the bursae and synovial sheaths. Pericardial, Peritoneal, and Pleural Secretions. — In the normal condition of the true serous membranes, the amount of secretion is very small ; so small, indeed, that it never has been obtained in quantity sufficient for ultimate analysis. It is not true that these membranes produce merely a vaporous exhalation. Their secretion is always liquid, and, small as it is in quantity, it can be found in the pericardial sac, and sometimes in the lower part of the ab- dominal cavity. As the only apparent function of these fluids is to moisten the membranes, so that the opposing surfaces can move over each other without undue fric- SEROUS SECRETIONS. 4:3 tion, only enough fluid is secreted to keep these surfaces in a proper condition. The error frequently committed by authors, in describing the serous exhalations as vaporous, is due to the fact that a vapor is generally given off when the serous cavities are exposed, either in a living animal or in one recently killed. This vaporous exhalation takes place after exposure of the parts ; but if the cavities be observed without exposing the serous surfaces to the air, a certain quantity of liquid can be detected. Colin always found liquid in the peritoneal, pericardial, and pleural cavities of animals recently killed or opened during life. In these cavities the opposite surfaces of the serous membrane were either in contact, or the space between them was filled with liquid. In one of the small ruminants, he removed the muscles and the elastic tunic from the lower part of the abdomen, exposing the transparent peritoneum, and through this membrane could see liquid collected in the dependent parts.1 As far as has been ascertained, the secretions of the dif- ferent serous membranes bear a close resemblance to each other. They are either colorless, or of a slight amber tinge, alkaline in reaction, and have a specific gravity of from 1012 to 1020. Their composition resembles that of the serum of the blood, except that the proportion of water is very much greater. They contain albumen, chlorides, car- bonate and phosphate of soda, and a little glucose. These facts are the result of observations upon the serous fluids of some of the inferior animals ; 3 and it is exceedingly difficult to obtain the normal fluids from the human subject. The elaborate analyses which are sometimes given of the fluids from the different serous cavities in the human subject are the results of examinations of large morbid accumulations.8 1 COLIN, Traite de physiologic comparee dts animaux domestiqucs, Paris, 1856, tome ii., p. 438. 3 COLIN, loc. cit. * ROBIN, Lemons sur les humeurs, Paris, 1867, p. 262, et seq. This author 44 SECRETION. The normal quantity of pericardial fluid in the human subject is generally estimated at from one to two flui- drachms. Colin found that the pericardial sac of the horse contained from two and a half to three and a half fluid- ounces, the cavity being exposed immediately after the death of the animal from haemorrhage. The quantity of fluid found in the peritoneal cavity in horses killed in this way was from ten to thirty-four fluid- ounces. The quantity of fluid in the pleural cavity in the same animal was from three and a half to seven fluidounces.1 These estimates are simply approximative ; but they give an idea of the normal quantity of liquid which may reason- ably be supposed to exist in the serous cavities of the human subject. Judging from the weight of a man of ordinary size as compared with that of a horse, it may be stated, in general terms, that the pericardial sac contains from two and a half to three and a half fluidrachms ; the peritoneal cavity from one to four fluidounces ; and the pleural sac from three and a half to seven fluidrachms. The fluid in the cavity of the tunica vaginalis is small in quantity, and resembles in every respect the peritoneal secre- tion. The cephalo-rachidian, or subarachnoid fluid will be described in connection with the anatomy of the cerebro- spinal nervous system. Synovial Fluid. — Although there is a certain similarity between the serous and the synovial membranes, their secre- tions differ very considerably in their physical and chemical characters. Like the serosities, the synovial fluid has simply a mechanical function ; but it is more viscid, and contains a larger proportion of organic matter than the serous fluids. The quantity of fluid in the joints is sufficient to lubricate has collected the latest analyses of the pleural fluid, the pericardial fluid, the fluid of ascites, and the fluid of hydrocele. 1 COLIN, loc. cit. SYNOVIAL FLUID. 45 freely the articulating surfaces. In a horse of medium size and in good condition, examined immediately after death, Colin found 1*6 fluidrachms in the shoulder-joint; 1*9 drachms in the elbow-joint ; 1'6 drachms in the coxo-fernoral articulation ; 2*2 in the femoro-tibial ; and 1*9 in the tibio- tarsal.1 When perfectly normal, the synovial fluid is either color- less or of a pale yellowish tinge. It is so viscid that it is with difficulty poured from one vessel to another. This peculiar character is due to the presence of an organic sub- stance called synovine. When this organic matter has been extracted and mixed with water, it gives to the fluid the peculiar viscidity of the synovial secretion. The reaction of the fluid is faintly alkaline, on account of the presence of a small proportion of carbonate of soda. The fluid, espe- cially when the joints have been much used, usually con- tains in suspension pale epithelial cells and a few leucocytes. The following is the composition of the synovial fluid of the human subject : a Composition of the Synovial Fluid. Water 928'00 Synovine (called albumen) 64'00 Principles of organic origin (belonging to the second class of Robin) not estimated. Fatty matter 0'60 Chloride of sodium \ 6'00 Carbonate of soda Phosphate of lime 1'50 Ammonio-magnesian phosphate traces. The observations of Frerichs indicate considerable vari- ations in the composition and general characters of the synovial fluid, dependent upon use of the joints. In a stall- fed ox the proportion of water to solid matter was 969*90 to 30'10; and in animals that took considerable exercise, 1 COLIN, op. cit.t tome ii., p. 440. 2 ROBIN, JLefons sur les humeurs, Paris, 1867, p. 276. 4:6 SECRETION. the proportions were 948*54: of water to 51*4:6 of solid matter. In the latter the fluid was more viscid, and contained a larger proportion of synovine with a smaller proportion of salts. It was also more deeply colored, and contained a larger number of leucocytes.1 Like the serous fluids, the synovial secretion is produced by the general surface of the membrane and not by any special organs. The folds and fringes which have been described were supposed at one time to be most active in secreting the organic matter, but there is no evidence that they have any such office. The aqueous humor of the eye and the fluid found in the labyrinth of the internal ear resemble the serous secretions in many regards ; but these fluids, with the vitreous humor, will be considered in connection with the physiological anat- omy of the eye and the ear. Mucus. Mucous Membranes. — The mucous membranes in dif- ferent situations present important peculiarities in structure, many of which have already been considered. We have described, in detail, in the preceding volumes, the mucous membrane of the air-passages and of the alimentary canal, in connection with the subjects of respiration and digestion ; and the membranes in other parts will necessarily be de- scribed in treating of the physiology of the organs in which they are found. It will be sufficient at present to take a general view of the structure of these membranes and the mechanism of the production of the various fluids known under the name of mucus. A distinct anatomical division of the mucous membranes may be made into two classes, as follows : First, those pro- vided with pavement-epithelium ; and second, those provided 1 FRERICHS, in WAGNER, Handworterbuch der Physiologic, Braunschweig, 1846, Band iii., S. 467. MUCUS. 47 with columnar, or conoidal epithelium. All of the mucous membranes line cavities or tubes communicating with the exterior by the different openings in the body. The following are the principal situations in which the first variety of mucous membranes, covered with pavement- epithelium, are found : The mouth, the lower part of the pharynx, the oesophagus, the conjunctiva, the female ure- thra, and the vagina. In these situations the membrane is composed of a chorion made up of inelastic and elastic fibrous tissue, a few fibro-plastic elements, with capillaries, lym- phatics, and nerves. The elastic fibres are small and quite abundant. The membrane itself is loosely united to the subjacent parts by areolar tissue. The chorion is provided with vascular papilla, more or less marked ; but in all situ- ations, except in the pharynx, the epithelial covering fills up the spaces between these papillse, so that the membrane pre- sents a smooth surface. Between the chorion and the epithelium, is an amorphous basement-membrane. The mu- cous glands open upon the surface of the membrane by their ducts, but the glandular structure is situated in the submu- cous areolar tissue. These glands have many of them been described in connection with the mucous membrane of the mouth, pharynx, and oesophagus.1 They are generally sim- ple racemose glands, presenting a collection of follicles ar- ranged around the extremity of a single excretory duct, lined or filled with rounded, nucleated epithelium. The pavement-epithelium covering these membranes ex- ists generally in several layers, and presents great variety, both in form and size. The most superficial layers are of large size, flattened, and irregularly polygonal. The deeper layers are smaller and more rounded. The size of these cells is from g-^j- to -g-j-^ of an inch. The cells are pale, slightly granular, and possess a small, ovoid nucleus, with one or two nucleoli. The second variety of mucous membranes, covered with 2 See vol. ii., Digestion, p. 166. 48 SECRETION. columnar epithelium, is found lining the alimentary canal below the cardiac orifice of the stomach, the biliary pas- sages, the excretory ducts of all the glands, the nasal pas- sages, the upper part of the pharynx, the uterus and Fallo- pian tubes, the bronchi, the Eustachian tubes, and the male urethra. In certain situations this variety of epithelium is provided on its free surface with little hair-like processes called cilia. During life the cilia are in constant motion, producing a current always in the direction of the mucous orifices. Ciliated epithelium is found throughout the nasal passages, commencing about three-quarters of an inch within the nose ; the upper part of the pharynx ; the posterior surface of the soft palate ; the Eustachian tube ; the tym- panic cavity ; the larynx, trachea, and bronchial tubes, un- til they become less than -fa of an inch in diameter ; the neck and body of the uterus ; the Fallopian tubes ; the in- ternal surface of the eyelids, and the ventricles of the brain. This variety of mucous membrane is formed of a chorion, a basement-membrane, and epithelium. The chorion is com- posed of inelastic and elastic fibres, with fibro-plastic ele- ments, a few unstriped muscular fibres, amorphous matter, vessels, nerves, and lymphatics. It is less dense and less elastic than the chorion of the first variety, and is generally more closely united to the subjacent tissue. The surface of these membranes is generally smooth, the only exception be- ing the mucous membrane of the pyloric portion of the stomach and the small intestines. These membranes are all provided with follicular glands, extending through their entire thickness and terminating in rounded extremities, sometimes single and sometimes double, which rest upon the submucous structure. Many of them are provided also with simple racemose glands, the ducts passing through the membrane, the glandular structure being situated in the submucous areolar tissue.1 1 See vol. i., Respiration, p. 361, for a description of the glandular organs MTCUS. 49 The columnar epithelium covering these membranes rests upon an amorphous structure, called basement-membrane. It generally presents but few layers, and sometimes, as in the intestinal canal, there is only a single layer. The cells are prismoidal, with a large free extremity, and a pointed end which is attached. The lower strata of cells are shorter and more rounded than those in the superficial layer. The cells are pale, very closely adherent to each other by 'their sides, and provided with a moderate-sized, oval nucleus with one or two nucleoli. The length of the cells is from -g^-g- to -g-J-g- of an inch, and their diameter from ao100 to 2£do of an inch. When villosities exist on the surface of the mem- branes, the cells follow the elevations and do not fill up the spaces between them, as in most of the membranes covered with pavement-epithelium. The mucous membrane of the urinary bladder, the ureters, and the pelvis of the kidneys, cannot be classed in either of the above divisions. They are covered with mixed epithelium, presenting all varieties of form between the pavement and the columnar, some of the cells being caudate and quite irregular. Mechanism of the Secretion of Mucus. — Nearly every one of the great variety of fluids known under the name of mucus is composed of the products of several different glan- dular structures. According to Robin, mucus proper is pro- duced by the epithelial cells of that portion of the membrane situated on the surface, between the opening of the so-called mucous follicles or glands ; * while the secretion of these special glandular organs always possesses peculiar properties. It is undoubtedly true that certain membranes which do not possess glands, as the mucous lining of the ureters and a great portion of the urinary bladder, are capable of secreting of the air-passages ; and vol. ii., Digestion, pp. 212, 313, and 389,. for a descrip. tion of the glands of the stomach and intestines. 1 ROBIX, Lefon* stir les humeurs, Paris, 1867, p. 438. 4 50 SECRETION. mucus. The mucous membrane of the stomach produces an alkaline, viscid secretion, during the intervals of digestion, when the gastric tubules do not act ; and the gastric tubules, during digestion, secrete a fluid of an entirely different char- acter. The fluid produced by the follicles of the small in- testine likewise has peculiar digestive properties. These circumstances, and the fact that the entire extent of the mu- cous membranes is covered with more or less secretion, show that the general epithelial covering of these membranes is capable of secreting a fluid which forms one of the constitu- ents of what is ordinarily recognized as mucus. It is im- possible, however, to separate the secretion of the superficial layer of cells from the other fluids that are found on the mucous membranes ; and it will be more convenient to re- gard as mucus, the secretion which is found upon mucous membranes, except when, as in the case of the gastric or the intestinal juice, we can recognize a special fluid by certain distinctive physiological properties. In the membranes covered with cylinder-epithelium, which are usually provided with numerous simple follicles, the se- cretion is produced mainly by these follicles, but in part by the epithelium covering the general surface. The mem- branes covered with pavement-epithelium usually contain but few follicles, and are provided with simple racemose glands situated in the submucous structure, which are to be regarded rather as appendages to the membrane. The secre- tion is here produced by the epithelium on the free surface, and is always mixed with fluids resulting from the action of the mucous glands. There is nothing to be said with regard to the mechanism of the secretion of mucus beyond what has already been stated in connection with the general mechanism of secretion. All the mucous membranes are quite vascular, and the cells covering the membrane and lining the follicles and glands at- tached to it have the property of taking from the blood the materials necessary for the formation of the secretion circus. 51 These principles pass out of the cells upon the surface of the. membrane in connection with water and inorganic salts in variable proportion. Many of the cells themselves are des- quamated, and are found in the secretion, together with a few leucocytes, which are produced upon mucous surfaces with great facility. Composition and Varieties of Mucus. — In comparing the secretions of the different mucous membranes, each one will be found to possess certain distinctive peculiarities, more or less marked ; but there are certain general characters which belong to all varieties of mucus. The fluid is usually a mixture of the secretion from the simple membrane and the product of its follicles or glandular appendages, and al- ways contains a certain amount of desquamated epithelium ; and it is frequently possible, from the microscopical charac- ters of the epithelium, to indicate the part by which any given specimen of mucus was secreted. This desquamation of epithelium must not be regarded as a necessary condition of the secretion of mucus, any more than the desquamation of the epidermic scales is to be regarded as a condition neces- sary to the secretion of perspiration or sebaceous matter. It is a property of the epidermis and the epithelial covering of mucous membranes to be regenerated by the formation of new cells from below, the effete structures being thrown off, and the admixture of these with mucus is simply accidental. The leucocytes, formerly called mucus-corpuscles, are the result of irritation of the mucous membrane, and are not constant constituents of normal mucus. All the varieties of mucus are more or less viscid ; but this character is very variable in the secretions from differ- ent membranes, in some of them the secretion being quite fluid, and in others almost semisolid. The different kinds of mucus vary considerably in general appearance. Some of them are perfectly clear and colorless ; but the secretion is generally grayish and semitransparent. 52 SECRETION. Examined by the microscope, in addition to the mixture of epithelium and occasional leucocytes, which give to the fluid its semiopaque character, the mass of the secretion presents, a very finely striated appearance, as though it were composed of thin layers of a nearly transparent substance, with many folds. These delicate striae do not usually interlace with each other, and are rendered more distinct by the action of acetic acid. This appearance, with the peculiar effect of the acid, is characteristic of mucus. Some varieties of mu- cus present very fine, pale granulations and a few small glob- ules of oil. On the addition of water, mucus is somewhat swollen, but is not dissolved. An exception to this is the secretion of the conjunctival mucous membrane, which is coagulated on the addition of water. As a rule, the reaction of mucus is alkaline ; the only exception to this being the vaginal mucus, which is very fluid and distinctly acid. It is exceedingly difficult to get an exact idea of the prox- imate composition of normal mucus, from the fact that the quantity secreted by the membranes in their natural condi- tion is very small, being just sufficient to lubricate their surface. All varieties, however, contain a peculiar organic principle, called mucosine, which gives the fluid its peculiar viscidity They likewise present a considerable variety of inorganic salts ; as the chlorides of sodium and potassium, alkaline lactates, carbonate of soda, phosphate of lime, a small proportion of the sulphates, and, in some varieties, traces of iron and silica.1 Of all these constituents, mucosine is the most important, as it gives to the secretion its characteristic properties. Like all other organic nitrogenized principles, mucosine is coagula- ble by various reagents. It is imperfectly coagulated by heat ; and after desiccation can be made to assume its peculiar con- 1 SIMON, Animal Chemistry with reference to the PJiysiology and Pathology of Man, Philadelphia, 1846, p. 351. MUCUS. 53 sistence by the addition of a small quantity of water. It is coagulated by acetic acid and by a small quantity of the strong mineral acids, being redissolved in an excess of the latter. It is also coagulated by strong alcohol, forming a fibrinous clot soluble in hot and cold water. Mucosine may be readily isolated by adding water to a specimen of nor- mal mucus, filtering, and precipitating with an excess of alcohol. If this precipitate, after having been dried, be ex- posed to water, it assumes the viscid consistence peculiar to mucosine. This property serves to distinguish it from albumen and other organic nitrogenized principles. Nasal Mucus. — The nasal mucus, being subject to so many changes from irritation of the Schneiderian membrane, presents considerable variation in its appearance and compo- sition. Under perfectly normal conditions, it is very viscid, clear or slightly opaque and grayish, and strongly alkaline. It always contains more or less columnar epithelium. In its behavior to various reagents, it presents the characteristics which we have ascribed to the secretions of the mucous membranes generally. The following is the composition of the normal secretion : Composition of Nasal Mucus? Water 933'00 to 947'00 Mucosine (with a trace of albumen ? ) 53'30 " 54'80 Lactate of soda (?) 1-00 " 5'00 Organic crystalline principles 2*00 " T05 Fatty matters and cholesterine not estimated 5 '01 Chlorides of sodium and potassium 5 '60 to 5*09 Calcareous and alkaline phosphates 3'50 " 2'00 Sulphate and carbonate of soda 0:90 not estimated. Bronchial and Pulmonary Mucus. — This is the secre- tion of the general mucous surface of the larynx and bron- chial tubes, mixed with the products of the glands situated in the substance of these membranes and in the submucous 1 ROBIN, Le?ons sur les humeurs, Paris, 1867, p. 450. 54 SECRETION. tissue. In addition to this secretion, there is an exhala- tion of watery vapor containing traces of organic matter, coming from the air-cells and the bronchial tubes less than -gij of an inch in diameter, which are not provided with mu- cous glands. This variety of mucus is alkaline and is quite similar to nasal mucus in its appearance and general char- acters. The following is an analysis, by Nasse, of the secre- tion expectorated in the morning by a healthy man : Composition of Bronchial and Pulmonary Mucus.1 Water 955-520 Hucosine, with a little albumen 23*754 Watery extract 8-006 Alcoholic extract 1*810 Fat 2-887 Chloride of sodium 5'825 Sulphate of soda 0'400 Carbonate of soda 0'198 Phosphate of soda 0*080 Phosphate of lime, with traces of iron 0'974 Carbonate of lime 0*291 Silica and sulphate of lime 0'255 1,000-000 Mucus secreted l>y the Mucous Membrane of the Ali- mentary Canal. — Throughout the alimentary canal, from the mouth to the anus, the lining membrane secretes a cer- tain quantity of mucus, which does not differ very much from the mucus found in other situations. This secretion appears to take place independently of the act of digestion, and the mucus in most parts of the tract is not known to possess any peculiar digestive properties. By ligating all of the salivary ducts, the buccal mucus has been procured. This secretion is produced by the cells covering the general surface of the membrane, and is mixed with the secretion of the iso- lated follicular and racemose glands of the mouth. An ana- 1 NASSE, Ueber die Bestandtheile des normalen Schleims der Luftwege. — Jour- nal fur praktische Chemie, Leipzig, 1843, Bd. xxix., S. 65. MUCUS. 55 logous secretion is produced by the mucous membrane of the pharynx and oesophagus.1 During the intervals of di- gestion, a viscid, alkaline secretion covers the mucous mem- brane of the stomach. The digestive secretions of the small intestine are so viscid that it has been found impossible to separate them from the true mucous secretion ; but un- doubtedly a secretion of ordinary mucus is constantly taking place from the lining membrane of both the small and the large intestine. This secretion probably has a purely me- chanical function, serving to lubricate the membranes and facilitate the movements of the opposing surfaces against each other. The mucous membrane of the gall-bladder produces quite an abundant secretion ; but this is always mixed with the bile, and will be considered in connection with the composi- tion of this fluid, though it is not known to possess any pe- culiar properties. Mucus of the Urinary Passages. — A small quantity of mucus is secreted by the urinary passages. This is present in the normal urine, in the form of a very slight, cloudy de- posit, which forms after the urine has been allowed to stand for a few hours. A certain amount of secretion takes place from the mucous membrane of the bladder, which, as we have seen, does not possess glands except near the neck. This secretion takes place in very small quantity, and may be recognized in the urine by the ordinary microscopical characters of mucus. Jfu-cus of the Generative Passages. — The vagina secretes a small quantity of mucus, which differs from the secretions of the other mucous membranes in being distinctly acid and almost entirely wanting in viscidity. The mucus of the neck of the uterus is clear, viscid, and distinctly alkaline. This is ordinarily produced in small quantity, but is very 1 See vol. ii., Digestion, p. 166. 56 SECRETION. abundant during pregnancy. It is the result of the action chiefly of the large, rounded glands found in this situation. The mucus of the body of the uterus and of the Fallopian tubes is alkaline, of a grayish color, and slightly viscid. The secretions of these parts are greatly modified during menstruation. These considerations, however, belong prop- erly to the subject of generation, and will be taken up more fully in another volume. Conjunctival Mucus. — A small quantity of a viscid se- cretion constantly covers the conjunct! val mucous membrane, and is a mixture of the secretion of the membrane itself with the fluid produced by the little mucous glands found near the internal angle of the eye. A peculiarity of this variety of mucus, mentioned by Robin, is that it becomes white, like coagulated albumen, by the action of pure water.1 A peculiarity of the mucus from the conjunctiva, the urethra of the male, and the vagina, is that they readily be- come virulent when secreted in abnormal quantity. They then contain a large number of leucocytes, and have a more or less puriform character ; but the virulent principle is con- tained in the clear liquid. General Function of Mucus. — The smooth, viscid, and adhesive character of mucus, forming, as this fluid does, a coating for the mucous membranes, serves to protect these parts, enables their surfaces to move freely one upon the other, and modifies to a certain extent the process of absorp- tion. This function is entirely independent of the function of some of the mucous glands, as the follicles of Lieberkiihn, which produce secretions only at particular times. Aside from the mechanical functions of mucus, it has been shown that this fluid, in connection with the epithelial covering of the mucous membranes, is capable of preventing the absorption of certain principles. It is well known, for 1 ROBIN, Lemons sur les humcurs, Paris, 1867, p. 447. SEBACEOUS FLUIDS. 57 example, that venoms may be applied with impunity to certain mucous surfaces, while they produce poisonous effects if introduced into the circulation. These agents are not neutralized by the secretions of the parts, for they will produce their characteristic effects upon the system when removed from the mucous surfaces and introduced into the circulation ; and it is reasonable to suppose that the mucous membranes are capable of resisting their absorption. ' This fact is proven by the following interesting experiment de- tailed by Robin : Let an endosmometer be constructed, using a fresh mucous membrane, on the surface of which the epithelium and layer of mucus remain intact, and in the interior of the apparatus, place a saccharine solution, and let the mem- brane be exposed to a solution containing some venomous fluid. The liquid will mount in the interior of the ap- paratus, but the poison will not penetrate the membrane. If the mucus and epithelium be now removed with the finger-nail from, even a small portion of the membrane, the poison will immediately pass through that part of the mem- brane, and an animal may be killed with the fluid which now penetrates into the interior of the endosmometer.1 These facts show that mucus is an important secretion. It not only has a useful mechanical function, but it is in all probability closely connected with some of the phenomena of elective absorption which are so often observed, particu- larly in the alimentary canal. Sebaceous Fluids. The general cutaneous surface is constantly lubricated by a small quantity of a peculiar oily secretion, called sebum, or sebaceous matter. This secretion is somewhat modified in certain situations, and an analogous fluid is pro- duced by glands of a peculiar structure opening into the ' ROBIN, Lemons sur ks humeurs, Paris, 1867, p. 439. 58 SECRETION. external meatus of the ear. Another fluid, very much like the ordinary sebaceous matter, is smeared upon the edges of the eyelids. These secretions, called respectively cerumen and Meibomian fluid, resemble the secretion of the ordinary sebaceous glands sufficiently to be classed with it. Physiological Anatomy of the Sebaceous, Ceruminous, and Meibomian Glands. — The true sebaceous glands are found in all parts of the body that are provided with hair ; and as nearly every part of the general surface presents either the long, the short, or the downy hairs, these glands are very generally distributed. They exist, indeed, in greater or less numbers in all parts of the skin, except the palms of the hands and the soles of the feet. In the labia minora in the female, and in portions of the prepuce and glans penis of the male, parts not provided with hair, small racemose sebaceous glands are found, which produce secre- tions differing somewhat from that formed by the ordinary glands. The glands in the areola of the nipple in the female are very large, and are connected with small, downy hairs. Kolliker has observed these glands, not connected with hairs, upon the nipple of the male.1 Nearly all of the sebaceous glands are either simple racemose glands, that is, presenting a number of follicles connected with a single excretory duct, or compound race- mose glands, presenting several ducts, with their follicles, opening by a common tube. Although there is this differ- ence in the size and arrangement of the glands of the gen- eral surface, they secrete essentially the same fluid, and their anatomical differences consist simply in a multiplication of follicles. The differences in the size of the sebaceous glands bear a certain relation to the size of the hairs with which they are connected ; and, as a rule, the largest glands are connected with the small, downy hairs. These distinctions in size are 1 KOLLIKER, Handbuch der Gewebelehre des Menschen, Leipzig, 1867, S. 571. SEBACEOUS FLUIDS. 59 so marked, that the glands may be divided into two classes ; viz., those connected with the long hairs of the head, face, chest, axilla, and genital organs, and the coarse, short hairs, and those connected with the fine, downy hairs. A few small simple follicles are found in the parts not provided with hairs.1 The glands connected with the larger hair-follicles are of the simple racemose variety, and are from -^ to ^ of an inch in diameter. From two to five of these glands are gen- erally found arranged around the follicle. They discharge their secretion at about the junction of the lower third with the upper two-thirds of the hair-follicle.2 The follicles of the long hairs of the scalp are generally provided each with a pair of sebaceous glands, measuring from y^-g- to ^ of an inch in diameter. Encircling the hairs of the beard, the chest, axilla, and genital organs, are large glands, some of them JL of an inch in diameter, arranged in groups of from four to eight. The glands connected with the follicles of the small, downy hairs, are so large, compared with the hair-follicles, that the latter seem rather as appendages to the glandular structure. These glands are of the compound racemose variety, and present sometimes as many as fifteen culs-de- sac. The largest are found on the nose, the ear, the carun- cula lachrymalis, the penis, and the areola of the nipple, where they measure from -^ to -^ of an inch. The glands connected with the downy hairs of other parts are usually smaller. The glands of Tyson, situated upon the corona of the glans penis and behind, upon the cervix, are sebaceous glands of the compound racemose variety.* The minute structure of the sebaceous glands is very 1 KOLLIKER, Handbuch der Gewebelehre des Mensclien, Leipzig, 1867, S. 146. 2 SAJPEY, Traite (Tanatomie descriptive, Paris, 1852, tome ii., p. 478. 3 A very full and satisfactory account of the distribution and general anat- omy of the sebaceous glands is to be found in KOLLIKER, Manual of Human Microscopic Anatomy, London, 1860, p. 135, d seq., and in the later German edition, Leipzig, 1867, S. 146, et seq. 60 SECRETION. simple. The follicles which compose the simple glands, and the follicular terminations of the simple and compound race- mose glands, are formed of a delicate, structureless or slightly granular membrane, with an external layer of inelastic and small elastic fibres, and are lined by cells. Next the mem- brane the cells are polyhedric, pale, and granular, most of FIG. i. them presenting a nucleus and nu- cleolus; but the follicle itself con- tains fatty granules and the other constituents of the sebaceous mat- ter, with cells filled with fatty particles. These cells abound in the sebaceous matter as it is dis- charged from the duct. The great quantity of fatty granules and globules found in the ducts and follicles of ' the sebaceous glands renders them dark and opaque when examined with the microscope by transmitted light, and their ap- pearance is quite distinctive. The larger glands are surrounded with capillary blood-vessels. The ceruminous glands of the ear produce a secretion resembling the sebaceous matter in many re- gards, but in their anatomy they are almost identical with the su- doriparous glands. They belong to the variety of glands called tubular, and consist of a nearly straight tube which pene- trates the skin, and a rounded or ovoid coil situated in the subcutaneous structure. These glands are found only in the cartilaginous portion of the external meatus, where they exist in great numbers. They are rather more numerous in the inner than in the outer half of the meatus. • IOS'25 Oleates and margarates of potassa and of soda, ) Chloride of sodium, *| Hydrochlorate of ammonia, t ..„_ Phosphate of soda and of lime, [ ' Ammonio-magnesian phosphate, J — ROBIN, Lemons sur Us humeurs, Paris, 1867 p. 590. 00 . SECRETION. The microscopical examination of the vernix caseosa is interesting from an anatomical point of view, and possesses considerable importance in certain medico-legal questions. The cells are polyhedric in form, somewhat flattened from mutual compression, and have a diameter of from 12100 to -5^5- of an inch. Their angles are irregular and rounded, not possessing that sharpness of definition which charac- terizes the epidermic cells of the foetus. They are colorless, transparent, very often folded upon themselves, and have no nuclei. The cells themselves are very slightly granular, but a few dark fatty granules sometimes adhere to their exterior. These cells have no analogy with the ordinary epidermic cells, but resemble rather the cells found in sebaceous collec- tions. They are regarded, therefore, by Robin, as derived entirely from the sebaceous glands.1 The secretion of these glands is discharged upon the surface, and disappears in great part, leaving a residue of altered epithelial cells. It is on account of the absence, to a great degree, of oily matter, that the vernix caseosa is not softened by gentle heat. The function of the vernix caseosa is undoubtedly pro- tective. If we attempt to make a microscopical preparation of the cells with water, it becomes evident that the coating is penetrated by the liquid with very great difficulty, even when mixed with it as thoroughly as possible. Indeed, we never observe at birth the peculiar effects of prolonged contact of the cutaneous surface with water. The protect- ing coating of vernix caseosa allows the skin to perform its functions in utero, and at birth, when this coating is removed, the surface is found in a condition perfectly adapted to ex- tra uterine existence. It is not probable that the vernix 1 ROBIN ET TARDIEU, Memoire sur Vexamin microscopique des laches formees par le meconium et Fenduitfcetal, pour servir d Thistoire medico-legale de V infan- ticide ; extraitdes Annales d> hygiene publique et de medecine legale, Paris, 1857, 2e serie, tome vii. CERUMEN. 69 caseosa is necessary to facilitate the passage of the child into the world, for the parts of the mother are always sufficiently lubricated with mucous secretion. Cerumen. — A peculiar substance of a waxy consistence is secreted by the glands that have been described, in the external meatus, under the name of ceruminous glands, mixed with the secretion of sebaceous glands connected with the short hairs in this situation. It is difficult to ascertain what share these two sets of glands have in the formation of the cerumen. Robin is of the opinion that the waxy portion of the secretion is produced entirely by the sebaceous glands, and that the convoluted glands, commonly known as the ceruminous glands, produce a secretion like the perspiration. He calls the latter, indeed, the sudoriparous glands of the meatus.1 This view is, to a certain extent, reasonable ; for the sebaceous matter is not removed from the meatus by fric- tion, as in other, situations, and would have a natural tenden- cy to accumulate. But the contents of the ducts of the ceru- minous glands differ materially from the fluid found in the ducts of the ordinary sudoriparous glands, containing gran- ules and fatty globules, such as exist in the cerumen. Al- though the glands of the ear are analogous in their structure, and, to a certain extent, in their secretion, to the perspira- tory glands, the fluid which they produce is peculiar. "We shall see, also, that the perspiratory glands of the axilla and of some other parts produce secretions differing somewhat from ordinary perspiration. As far as can be ascertained, the cerumen is produced by both sets of glands. The sebaceous glands attached to the hair-follicles probably secrete most of the oleaginous and waxy matter, while the so-called ceruminous glands produce a secretion of much greater fluidity, but containing a certain amount of granular and fatty matter. 1 ROBIN, Lefons sur les humeurs, Paris, 1867, p. 591. 70 SECRETION. The consistence and general appearance of cerumen are quite variable within the limits of health. When first secreted, it is of a yellowish color, about the consist- ence of honey, becoming darker and much more viscid upon exposure to the air. It has a very decided and bit- ter taste. It readily forms a sort of emulsive mixture with water. Examined microscopically, the cerumen is found to con- tain semisolid, dark granulations of an irregularly polyhe- dric shape, epithelium from the sebaceous glands, and epi- dermic scales, both isolated and in layers. Sometimes also a few crystals of cholesterine are found. Chemical examination shows that the cerumen is com- posed of oily matters fusible at a low temperature, a peculiar organic matter resembling mucosine, with salts of soda, and a certain quantity of phosphate of lime. The yellow coloring matter is soluble in alcohol ; and the residue after evapora- tion of the alcohol is very soluble in water, and may be pre- cipitated from its watery solution by the neutral acetate of lead or the chloride of tin. This extract has an exceedingly bitter taste. The cerumen lubricates the external meatus, accumu- lating in the canal around the hairs. Its peculiar bitter taste is supposed to be efficient in preventing the entrance of insects. Meibomian Secretion. — Yery little is known concerning any special properties of the Meibomian fluid, except that it mixes with water in the form of an emulsion more readily than the other sebaceous secretions.1 It is produced in small quantity, mixed with a certain amount of mucus and the secretion from the ordinary sebaceous glands attached to the eyelashes (ciliary glands), and the glands of the carun- cula lachrymalis, and smears the edges of the palpebral 1 ROBIN, op. cit., p. 592. MEIBOMTAN FLUID. 71 orifice. TJris oily coating on the edges of the lids, unless the tears be produced in excessive quantity, prevents their overflow upon the cheeks, and directs the excess of fluid into the nasal duct. CHAPTER III. MAMMAET SECRETION. Physiological anatomy of the mammary glands — Condition of the mammary glands during the intervals of lactation — Structure of the mammary glands during lactation — Mechanism of the secretion of milk — Conditions which modify the lacteal secretion — Influence of diet — Influence of liquid ingesta — Influence of alcoholic beverages — Influence of mental emotions — Quantity of milk — Properties and composition of milk — Specific gravity of milk — Coagulation of milk — Microscopical characters of milk — Composition of milk — Xitrogenized constituents of milk — Non-nitrogenized constituents of milk — Inorganic constituents of milk — Variations in the composition of milk — Colostrum — Composition of colostrum — Lacteal secretion in the newly-born — Composition of the milk of the infant. THE mammary glands are among the most remarkable organs in the economy; not only from the peculiar char- acter of their secretion, which is unlike the product of any other of the glands, but from the great changes which they undergo at different periods, both in size and structure. Rudimentary in early life, and in the male at all periods of life, these organs are fully developed in the adult female, only in the latter months of pregnancy and during lactation. It is true, that in the female, after puberty, the mammary glands undergo a marked and rapid increase in size ; but even then they are not fully developed, and if examined with the microscope, will be found to lack the essential ana- tomical characters of secreting organs. The physiological anatomy of the mammary glands consequently possesses MAMMARY GLAKDS. 73 peculiar interest, aside from the great importance of their secretion. It will be found convenient to consider these organs in three stages of development ; viz., in their rudimentary con- dition, as they exist in the male and in the female before puberty ; in the partially-developed state, as they are found in the unimpregnated female after puberty and during the intervals of lactation ; and finally, in the fully-developed condition, when milk is secreted. Physiological Anatomy of the Mammary Glands. The form, size, and situation of the mammae in the adult female are too well known to demand more than a passing mention. These organs are almost invariably double, and are situated on the anterior portion of the thorax over the great pectoral muscles. In women who have never borne children, they are generally firm, nearly hemispherical, with the nipple at the most prominent point. In women who have borne children, the glands, during the intervals of lactation, are usually larger, are held more loosely to the subjacent parts, and are apt to become flabby and pendu- lous. The areola of the nipple is also darker. Certain rare examples are on record of anomalies in the number and location of the mammary glands. In some in- stances three, four, and five distinct glands have existed instead of two ; * and some examples are related of extra- ordinary development of the mammary glands in the male, to such an extent as to afford sufficient nourishment for an infant.8 A remarkable case of malposition of a mammary gland is reported by Dr. Eobert, of Marseilles, in Magendie's 1 Reference to a number of these cases is made by Dr. Solly, in the Cyclo- pcedia of Anatomy and Physiology, London, 1839-1847, vol. iii., p. 251. 8 Quite a number of cases of this kind are on record, many of them well authenticated. Dr. Dunglison gives a full account of several instances of lac- tation in the male, attested by competent medical observers. (DUNGLISON, Human Physiology, Philadelphia, 1856, vol. ii., p. 520.) 74: SECRETION. Journal of Physiology. In this case there was a well-formed mammary gland on the external surface of the left thigh, about four inches below the great trochanter. The mam- mary glands upon the chest performed their function with regularity, and were normal in all respects ; but the gland upon the thigh secreted during lactation such a quantity of milk, that the woman had nourished all her children, seven in number, indifferently from the three glands. She had nursed one of her children in this way for thirty- three months. It is a remarkable fact, that the mother of this woman had three mammary glands, one on the left side of the chest and two on the right. This case is perfectly authentic, and was reported on by MM. Chaussier and Ma- gendie, a committee from the French Academy of Sci- ences.1 In many works on physiology, instances of unusual lac- tation are quoted ; but although the time and duration of the process are modified, the character of the secretion is not altered. A case is reported as occurring in this country, in which lactation continued in a woman sixty-five years of age.2 At birth, in both sexes, the mammary glands are nearly as fully developed as at any time before puberty. They make their appearance about the fourth month, in the form of little elevations of the structure of the true skin, which soon begin to send out processes destined to be developed into the lobes of the glands. At birth the glands measure hardly more than one-third of an inch in diameter. At this time there are from twelve to fifteen lobes in each gland, and every lobe is penetrated by a duct, with but few 1 CHAUSSIER ET MAGENDIE, Rapport fait d V Academic des Sciences sur une observation de M. le Dr. Robert, de Marseille, relative d une femme qui a allaite plusieurs enfans avec une mamelk situee d la cuisse gauche. — Journal de physiologic, Paris, 1827, tome vii., p. 175. 2 DCNGLISON, Human Physiology, Philadelphia, 1856, vol. ii., p. 518. The reader is referred to the work of Dr. Dunglison for an account of a number of very curious instances of unusual lactation. MAMMARY GLANDS. 75 branches, composed of fibrous tissue and lined with colum- nar epithelium. The ends of these ducts are frequently somewhat dilated; but what have been called the gland- vesicles do not make their appearance before puberty. In the male the glands are from one half an inch to two inches broad, and from ^ to J of an inch in thickness. In their structure, however, they present little if any difference from the rudimentary glands of the infant. As the period of puberty approaches in the female, the rudimentary ducts of the different lobes become more and more ramified. Instead of each duct having but two or three branches, the different lobes, as the gland enlarges, are penetrated by innumerable ramifications, which have gradually been developed as processes from the main duct. It is important to remember, however, that these branches are never so numerous nor so long during the intervals of lactation as they are when the organ is in full activity. The ordinary condition of the gland, as compared with its structure during activity, is that of atrophy. Condition of the Mammary Glands during the Intervals of Lactation. — At this time the gland is not a secreting organ. It presents the ducts, ramifying, to a certain extent, in the substance of the lobes into which the structure is di- vided, but their branches are short and possess but few of the glandular acini that are observed in every part of the organ during lactation. This difference in the structure of the gland is most remarkable; and as it passes from a secreting to a non-secreting condition at the end of lacta- tion, the ducts retract in all their branches, and most of the secreting culs-de-sac disappear. At this time the glandular tissue is of a bluish-white color, and loses the granular ap- pearance which it presents during activity. The ducts are then lined with a small, nucleated, pavement-epithelium, which is not found during the secretion of milk. These changes, pointed out by Robin, whose observations have 76 SECRETION. been verified and extended by Sappey,1 are confined almost exclusively to the secreting structure of the gland. The interstitial tissue remains about the same, the blood-vessels, only, being increased in number during lactation. As we are treating of the mammary glands as secreting organs, a full description of its structure is deferred until we come to con- sider it in a state of functional activity. Structure of the Mammary Glands during Lactation. — Between the fourth and the fifth month of utero-gestation, the mammary glands begin to increase in size ; and at term, they are very much larger than during the unimpregnated state. At this time the breasts become quite hard ; and the surface near the areola is somewhat uneven, from the great development of the ducts. The nipple itself is increased in size, the papillae upon its surface and upon the areola are more largely developed, and the areola becomes larger, darker, and thicker. The glandular structure of the breasts during the latter half of pregnancy becomes so far developed, that if the child be born at the seventh month, the lacteal secretion may generally be established at the usual period after parturition. Even when parturition takes pi ace at term, a few days elapse before secretion is fully established, and the first product of the gland, called colostrum, is very dif- ferent from the fully-formed milk. The only parts of the covering of the breasts that present any peculiarities are the areola and the nipple. The surface of the nipple is covered with papillae, which are very largely developed near its summit. It is covered by epithe- lium in several layers, the lower strata being filled with pigmentary granules. The true skin covering the nipples is composed of inelastic and elastic fibres, containing a large number of sebaceous glands, but no hair-follicles nor sudori- parous glands. According to Sappey, these glands, which are from eighty to one hundred and fifty in number, are always of the racemose variety, and never exist in the form 1 SAPPEY, Traite $ anatomic descriptive, Paris, 1857, tome iii., p. 697. MAMMARY GLANDS. 77 of simple follicles, as they are described by most anatomists.1 The nipple contains the lactiferous ducts, fibres of inelastic and elastic tissue, with an immense number of non-striated muscular fibres. The muscular fibres have no definite direc- tion, but are so numerous, that when they are contracted, the nipple becomes very firm and hard. The nipple, though it may thus become hard upon the application of cold or other stimulus, presents none of the anatomical characteris- tics of the true erectile organs, as is erroneously supposed by some authors ; and its hardening is simply due to contrac- tion of its muscular fibres.8 The areola does not lie, like the general integument covering the gland, upon a bed of adipose tissue, but is closely adherent to the subjacent glandular structures. The ' skin here is much thinner and more delicate than in other parts, and the pigmentary granules are very abundant in some of the lower" strata of epidermic cells, particularly dur- ing pregnancy. The true skin of the areola is composed of inelastic and elastic fibres, and lies upon a distinct layer of non-striated muscular fibres. The arrangement of the mus- cular fibres (sometimes called the sub-areolar muscle) is quite regular, forming concentric rings around the nipple. These fibres are supposed to be useful in compressing the ducts during the discharge of milk. The areolar presents nu- merous papillae, considerably smaller than those upon the nipple ; hair-follicles, containing small, rudimentary hairs ; sudoriparous glands ; and sebaceous glands connected with the hair-follicles. The sebaceous glands in this situation are very large, and their situation is indicated by little prominences at the surface of the areola, which are especi- ally marked during pregnancy. The gland itself is of the compound racemose variety. It is covered in front by a subcutaneous layer of fat, and posteriorly is enveloped in a fibrous membrane loosely at- 1 SAPPEY, Traite cT anatomic descriptive, Paris, 1857, tome iii., p. 594. 2 For the anatomy of the erectile tissues, see vol. i., Circulation, p. 336. 78 SECRETION. tached to the pectoralis major. A considerable amount of adipose tissue is also found in the substance of the gland, between the lobes. Separated from the adipose and fibrous tissue, the organ, is found divided into lobes, from fifteen to twenty-four in number. These, in their turn, are subdivided into lobules made up of a greater or less number of acini or culs-de-sac. The secreting structure is of a reddish-yellow color, and is distinctly granular, presenting a decided contrast to the pale and uniformly fibrous appearance of the gland during the intervals of lactation. If the ducts be injected from the nipple and be followed into the substance of the gland, each one will be found distributing its branches to a distinct lobe ; so that the organ is really made up of a number of glands, in their structure identical with each other. It will be most convenient, in studying the intimate structure of the gland, to begin at the nipple and follow out one of the ducts to the termination of its branches in the secreting culs-de-sac, The canals which discharge the milk at the nipple are called lactiferous, or galactophorous ducts. They vary in number from ten to fourteen. The openings of the ducts at the nipple are very small, measuring only from -fa to ^ of an inch. As each duct passes down, it enlarges in the nipple to -fa or -^ of an inch in diameter, and beneath the areola presents an elongated dilatation, from -J- to J of an inch in diameter, called the sinus of the duct.1 During lactation a considerable quantity of milk collects in these sinuses, which serve as reservoirs. Beyond the sinuses the calibre of the ducts is from -fa to -J- of an inch. They penetrate the differ- ent lobes, branching and subdividing, to terminate finally in the collections of culs-de-sac which form the acini. Most modern observers are agreed that there is no anastomosis be- tween the different lactiferous ducts, and that each one is distributed independently to one or more lobes. 1 KOLLIKER, Handbuch der Gewebelehre des Afenschen, Leipzig, 1867, S. 571. GLANDS. 79 The intimate structure of the lactiferous ducts is inter- esting and important. They are possessed of three distinct coats. The external coat is composed of anastomosing fibres of elastic tissue, with some fibres of inelastic tissue. The middle coat is composed of non-striated muscular fibres, ar- ranged longitudinally and existing throughout the duct, from its opening at the nipple to the secreting culs-de- sac. The internal coat is an amorphous membrane, lined with roundish or elongated cells during the intervals of lactation and even during pregnancy, but deprived of epi- thelium during the period when the lacteal secretion is most active.1 The acini of the gland, which are very numerous, are \isible to the naked eye, in the form of small, rounded gran- ules, of a reddish-yellow color. Between these acini there exist a certain quantity of the ordinary white fibrous tissue and quite a number of adipose vesicles. The presence of adi- pose tissiie in considerable quantity in the substance of the glandular structure is peculiar to the mammary glands. Each acinus is made up of from twenty to forty secreting vesicles, or culs-de-sac. These vesicles are irregular in form, often varicose, and sometimes enlarged and imperfectly bifur- cated at their terminal extremities. During lactation their diameter is from -%%-$ to yj-g- of an inch. During pregnancy, and when the gland has just arrived at its full development, the secreting vesicles are formed of a structureless membrane, lined 'with small, nucleated cells of pavement-epithelium. The nuclei are relatively large, ovoid, and embedded in a small amount of amorphous matter, so that they almost touch each other. Sometimes the epithelium is segmented, and sometimes it exists in the form of a continuous nucleated sheet. When the secretion of milk becomes active, the epi- thelium entirely disappears, and reappears as the secretion diminishes. This observation is due to Robin,8 and has an 1 SAPPEY, Traite cT anatomic descriptive, Paris, 1857, tome Hi., p. 697. 8 LITTRE ET ROBIX, Dictionnaire de medecine, Paris, 1865, Article, MameUe. 80 SECRETION. FIG. 4. important bearing upon the mechanism of the secretion of milk. During the intervals of lactation, as the lactiferous ducts become retracted, the glandular culs-de-sac disappear ; and in pregnancy, as the gland takes on its full development, the ducts branch and extend themselves, and the vesi- cles are gradually devel- oped around their ter- minal extremities. These changes in the develop- ment of the mammae at different periods are most remarkable, and are not observed in any other part of the glandular system.1 Mechanism of the Se- cretion of Milk. — With the exception of water and in- organic principles, all the Ducts and acini of the mammary piand. (LiT- important and character- TRfi ET ROBIN. Dictionnaire de medecine, i^l-ir* nrmefi-H-ionfe r»f -flm Paris, 1865, Article, Mamdle.) m, nipple; lstic Constituents Ol «, larger ducts ; r, small duct ; «, acini. milk &TQ formed ill the substance of the mam- mary glands. The secreting structures have the property of separating from the blood a great variety of inorganic principles ; and we shall see, when we come to study the composition of the milk more minutely, that it furnishes 1 Sir Astley Cooper, in his admirable monograph upon the anatomy and diseases of the breast, published in 1840, was the first to give any clear idea of the minute structure of the mammary glands. His observations, however, have been much extended by later anatomists. The paper on the breast has been republished in this country. COOPER, The Anatomy and Diseases of the Breast, with numerous plates. To which are added his various Surgical Papers, now first published in a collected form, Philadelphia, 1845. MILK. 81 all the inorganic matter necessary for the nutrition of the infant, containing, even, a small quantity of iron. Pre- cisely how the secreting vesicles separate the proper quan- tity of these principles from, the circulating fluid, we are unable, in the present state of our knowledge, to determine. It is unsatisfactory enough to say that the membranes of the vesicles have an elective action, but this expresses the extent of our information on the subject. The lactose, or sugar of milk, the caseine, and the fatty particles, are all produced, de novo, in the gland. The pecu- liar kind of sugar here found does not exist anywhere else in the organism. Even when the secretion of milk is most active, different varieties of sugar, such as glucose or cane- sugar, injected into the blood-vessels of a living animal, are never eliminated by the mammary glands, as they are by the kidneys ; and their presence in the blood does not influence the quantity of lactose found in the milk. All that can be said with regard to the formation of sugar of milk is, that it is produced in the mammary glands. The mechanism of its formation is not understood. Caseine is produced in the mammary glands, probably by a catalytic transformation of the albuminoid constituents of the blood. This principle does not exist in the blood, though its presence here has been indicated by some observ- ers. The substance in the blood that has been mistaken for caseine is undoubtedly albumen, which will not respond to some of the tests on account of the alkalinity of the fluid in which it is contained. It is well known that the caseine of milk is precipitated by an excess of sulphate of magnesia ; but the so-called caseine of the blood is not affected by this salt, and passes through it like albumen.1 The fatty particles of the milk are likewise produced in the substance of the gland, and the peculiar kind of fat which exists in this secretion is not found in the blood. The mechanism of the production of fat in the mammary 1 LONGET, Traite de physiologic, Paris, 1869, tome ii., p. 283. 6 82 SECRETION. glands is obscure. The particles are not produced in cells and set free by their rupture, by a process analogous to that which takes place in the formation of the fatty particles found in the sebaceous matter, for during the time when the secretion of milk is most active, the epithelium of the secreting culs-de-sac has entirely disappeared. The butter is produced by the action of the amorphous walls of the vesicles, in the same way, probably, that fat is produced by the vesicles of the ordinary adipose tissue. At least, this is all that is known regarding the mechanism of its pro- duction. As regards the mechanism of the formation of the peculiar and characteristic constituents of the milk, the mammary glands are to be classed among the organs of secretion, and not those of elimination or excretion; for none of these elements preexist in the blood, but all appear first in the substance of the glands. During the period of secretion, the glands receive a much larger supply of blood than at other times. Pregnancy favors the development of the secreting portions of the glands, but does not induce secretion. On the other hand, when pregnancy occurs during lactation, it diminishes, mod- ifies, and may arrest the secretion of milk. The secre- tion is destined, however, for the nourishment of the child, and not for use in the economy of the mother — an important point of distinction from all other secretions — and its produc- tion presents one or two interesting peculiarities. In the first place, the secreting action of the mammary glands is nearly continuous. When the secretion of milk has become fully established, while there may be certain periods when it is formed in greater quantity than at others, there is no absolute interim ttency in its production. Again, in all the other glandular organs, the epithelial cells found in their secreting portion seem to be the active agents in the production of the secretions ; but in the mam- mary glands, as we have already noted, the epithelium MILK. 83 entirely disappears from the secreting culs-de-sac during the period of greatest functional activity of the gland, and nothing is left to perform the work of secretion but the amorphous membrane of the vesicles. Conditions which modify the Lacteal Secretion. — Yery little is known concerning the physiological conditions -which modify the secretion of milk. When lactation is fully established, the quantity and quality of the milk secreted become adapted to the requirements of the child at differ- ent periods of its existence. In studying the composition of the milk, therefore, it will be found to vary considerably in the different stages of lactation. It is evident that, as the development of the child advances, a constant increase of nourishment is demanded ; and, as a rule, the mother is capable of supplying all the nutritive requirements of the infant for from eight to twenty months. During the time when such an amount of nutritive mat- ter is furnished to the child, the quantity of food taken by the mother is sensibly increased ; but observations have shown that the secretion of milk is not much influenced by the nature of the food. It is necessary that the mother should be supplied with good, nutritious articles ; but as far as solid food is concerned, there seems to be no great difference between a coarse and a delicate alimentation ; and the milk of females in the lower walks of life, when the general condition is normal, is fully as good as in women who are enabled to live luxuriously. It is, indeed, a fact gen- erally recognized by physiologists, that the secretion of milk is little influenced by any special diet, provided the alimenta- tion be sufficient and of the quality ordinarily required by the system, and that it contain none of the few articles of food which are known to have a special influence upon lac- tation. So long as the mother is healthy and well nourished, the milk will take care of itself; and the appetite is the surest guide to the proper variety, quality, and quantity of 84: SECRETION. food. It is very common, however, for females to become quite fat during lactation ; which shows that the fatty ele- ments of the food do not pass exclusively into the milk, but that there is a tendency, at the same time, to a deposition of adipose tissue in the ordinary situations in which it is found. It is a matter of common experience, that certain articles, such as acids and fermentible substances, often disturb the digestive organs of the child without producing any change in the milk, that can be recognized by chemical analysis. The individual differences in women, in this regard, are very great. There are certain medicinal substances which are some- times found to exert a powerful influence in diminishing or even arresting the secretion of milk, but a full consider- ation of these belongs to therapeutics. The same remark applies to the influence of electricity applied directly to the mammary glands. The statements with regard to solid food do not apply to liquids. During lactation there is always an increased demand for water and liquids generally; and if these be not supplied in sufficient quantity, the secretion of milk is diminished, and its quality is almost always impaired. It is a curious fact, which has been fully established by obser- vations upon the human subject and the inferior animals, that while the quantity of milk is increased by taking a large amount of simple water, the solid constituents are also increased, and the milk retains all of its qualities as a nutritive fluid. The late observations on this subject, by Dancel, illustrate very fully the unusual demand for liquids during lactation, and their influence upon the mammary secretion.1 Alcohol, especially when largely diluted, as in malt- liquors and other mild beverages, is well known to exert an influence upon the secretion of milk. Drinks of this kind 1 CANCEL, De I1 influence de Veau dans la production du lait. — Comptes rendus, Paris, 1865, tome Ixi., p. 243. MILK. 85 almost always temporarily increase the activity of the secre- tion, and sometimes produce a certain amount of effect upon the child ; but direct and accurate observations on the actual passage of alcohol into the milk are wanting. During lac- tation the moderate use of drinks containing a small propor- tion of alcohol is frequently beneficial, particularly in assist- ing the mother to sustain the unusual drain upon the system. There are, however, few instances of normal lactation in which their use is absolutely necessary. It has been conclusively shown that many medicinal articles administered to the mother pass unchanged into the mammary secretion, and therapeutists have sometimes at- tempted to produce the peculiar effects of certain remedies in this way in the child. This, however, can hardly be called a physiological action ; but it is interesting to note that some articles may be eliminated in the milk, while others pass into other secretions. This elective power we have already seen is possessed by many of the glands. Among the articles that pass readily into the milk may be mentioned, some of the salts of soda, chloride of sodium, the sesquioxide of iron, and the preparations of iodine. Dr. Eees detected iodine in the milk in a patient who had taken but forty-five grains of the iodide of potassium in five-grain doses three times daily.1 It is generally believed, from the effects upon the child of remedial agents administered to the mother, that very many articles of this class pass into the milk, but in such small quantity that they cannot be de- tected by the ordinary chemical tests. It is well known that the secretion of milk may be pro- foundly affected by violent mental emotions. This is the case with many other secretions, as the saliva, and the gastric juice. It is hardly necessary, however, to cite the numerous instances of modification or arrest of the secretion from this cause, which are quoted in many works. Yernois and Bec- 1 Cyclopaedia, of Anatomy and Physiology, London, 1839-1847, vol. iii., p. 362. 86 SECRETION. querel mention a very striking case, in which a hospital wet-nurse, who had lost her only child from pneumonia, b.ecame violently affected with grief, and presented, as a con- sequence, an immediate diminution in the quantity of her milk, with a great reduction in the proportion of salts, sugar, and butter. In this case the proportion of caseine was in- creased.1 Sir Astley Cooper mentions two cases in which the secretion of milk was instantaneously and permanently arrested from terror.3 These cases are types of numerous others, which have been reported by writers, of the effects of mental emotions upon secretion. In the present state of oar knowledge, we can only com- prehend the influence of mental emotions upon secretion, by assuming that they operate through the nervous system ; and in many of the glands, the influence of the nerves has been clearly demonstrated by actual experiment. Direct observa- tions, however, upon the influence of the nerves upon the mammary glands are few and unsatisfactory. The opera- tion of dividing the nerves distributed to these glands, which has occasionally been practised upon animals in lac- tation, has not been observed to produce any sensible dimi- nution in the quantity of the secretion.3 It is difficult, however, to operate upon all the nerves distributed to these organs. Quantity of Milk. — It is very difficult to form a reliable estimate of the average quantity of milk secreted by the hu- man female in the twenty-four hours. The amount undoubt- edly varies very much in different persons ; some women being able to nourish two children, while others, though ap- parently in perfect health, furnish hardly enough food for one. 1 VERNOIS ET BECQUEREL, Du lait cJiez la femme dans Tctat de sante et dans fetal de maladie, Paris, 1853, p. 73. 2 COOPER, The Anatomy and Diseases of the Breast, Philadelphia, 1845, p. 101. 3 LONGET, Traite de physiologic, Paris, 1869, tome ii., p. 291. MILK. 87 Cooper, as the result of direct observation, states that the quantity that can be drawn from a full breast is usually about two fluidounces.1 This may be assumed to be about the quantity contained in the lactiferous ducts when they are mod- erately distended. Lehmann, taking for the basis of his cal- culations the observations of Lamperierre,2 who found, as the result of sixty-seven experiments, that from fifty to sixty grammes of milk were secreted in two hours, estimates that the average quantity discharged in twenty-four hours is 1,320 grammes, or about 44*5 fluidounces.3 Robin estimates that the daily quantity is from thirty-four to one hundred fluidounces ; 4 but he does not give the data from which this estimate is formed. Taking into consideration the evi- dent variations in the quantity of milk secreted by different women, it may be assumed that the daily production is from two to six pints. Certain conditions of the female are capable of ma- terially influencing the quantity of milk secreted. It is evident that the secretion is usually somewhat increased within the first few months of lactation, when the progressive development of the child demands an increase in the quan- tity of nourishment. If the menstrual function become re- established during lactation, the milk is usually diminished in quantity during the periods, but sometimes it is not af- fected, either in its quantity or composition. Should the female become pregnant, there is generally a great diminu- tion in the quantity of milk, and that which is secreted is ordinarily regarded as possessing little nutritive power. In obedience to a popular prejudice, apparently well-founded, the child is usually taken from the breast as soon as preg- nancy is recognized. All of these conditions have been 1 COOPER, TJie Anatomy and Diseases of the Breast^ Philadelphia, 1845, p. 93. 2 LAMPERIERRE, Des moyens d reconnaitre la quantite et la qualite de la secre- tion lactee chez la fenime. — Comptes rendus, Paris, 1850, tome xxx., p. 174. 3 LEHMAXX, Physiological Chemistry, Philadelphia, 1855, vol. ii., p. 63. 4 ROBIN, Lecons sur les humeurs, Paris, 1867, p. 402. 88 SECRETION. closely studied by Yernois and Becquerel, with reference to their influence upon the composition of the milk ; and their observations will be fully considered in treating of the chem- istry of the mammary secretion. Authors have not noted any marked and constant variations in the quantity of milk in females of different ages. Properties and Composition of the Milk. The general appearance and characters of ordinary cow's milk are sufficiently familiar and may serve as a standard for comparison with the milk of the human female.1 Human milk is not so white nor so opaque as cow's milk, having ordinarily a slightly bluish tinge. The milk of different healthy women presents some variation in this regard. After the secretion has become fully established, the fluid possesses no viscidity, and is nearly opaque. It is almost inodorous, of a peculiar soft and sweetish taste, and when perfectly fresh, has a decidedly alkaline reaction. The taste of hu- man milk is sweeter than that of cow's milk. A short time after its discharge from the gland, the reaction of milk becomes faintly acid ; but this change takes place more slowly in human milk than in the milk of most of the inferior animals. The average specific gravity of human milk, according to Yernois and Becquerel, is 1032 ; though this is subject to considerable variation, the minimum of eighty-nine obser- vations being 1025, and the maximum, 1046.2 The observa- tions of most physiological chemists have shown that this average is nearly correct. Milk is not coagulated by heat, even after prolonged boiling ; but a thin pellicle then forms on the surface, which is probably due to the combined action of heat and the at- 1 The properties and composition of cow's milk have already been consid- ered in another volume. See vol. ii., Alimentation, p. 77, et seq. 2 VERXOIS ET BECQUEREL, Du lait chez lafemme, Paris, 1853, p. 14. MILK. 89 mosphere upon the caseine. Although a small quantity of albumen exists in the milk, this does not coagulate on the surface by the action of heat, for the scum does not form when the fluid is heated in an atmosphere of carbonic acid, or of hydrogen, or in a yacuum.1 AVhen the milk is coagulated by any substance acting upon the caseine, or when it coagulates spontaneously, it separates into a curd, composed of caseine with most of the fatty particles, and a nearly clear, greenish-yellow serum, called whey. This separation occurs spontaneously, at a yariable time after the discharge of the milk, taking place much more rapidly in warm than in cold weather. It is a curious fact that fresh milk is frequently coagulated during a thunder-storm, a phenomenon which has neyer been sat- isfactorily explained. On being allowed to stand for a short time, the milk separates, without coagulating, into two tolerably distinct portions, A large proportion of the globules rise to the top, forming a yellowish- white, and very opaque fluid, called cream, leaying the lower portion poorer in globules and of a decidedly bluish tint. In healthy milk the stratum of cream forms from one-fifth to one-third of the entire mass of the milk. In the human subject the skim-milk is not white and opaque, but is nearly as transparent as the whey. This is a yery good method of testing the richness of milk; and little graduated glasses, called lactometers, haye been, constructed for measuring the thickness of the layer of cream. The specific grayity of the cream from milk of the ayerage specific gravity of 1032 is about 1024. The specific gravity of the skim-milk is about 1034. Microscopical Characters of the Milk. — If a drop of milk be examined with a magnifying power of from three hun- dred to six hundred diameters, the cause of its opacity will be apparent. It contains an immense number of minute 1 ROBIN, Lemons surles humeurs, Paris, 186?, p. 388. 90 SECEETION. globules, of great refractive power, held in suspension in a clear fluid. These are known under the name of milk- globules, and are composed of margarine, oleine, and a fatty matter, peculiar to milk, called butyrine. In human milk the particles are perfectly spherical ; but in cow's milk they are often polyhedric from mutual compression. This differ- ence is due to the softer consistence of the butter in human milk, the globules containing a much larger proportion of oleine ; and if cow's milk be warmed, the particles also as- sume a spherical form. The human milk-globules measure from as^o0 to I21go of an inch in diameter. They are usually distinct from each other, but may occasionally become collected into groups without indicating any thing abnormal. In a perfectly nor- mal condition of the glands, when the lacteal secretion has become fully established, the milk contains nothing but a clear fluid with these globules in suspension. The propor- tion of fatty matter in the milk is from twenty-five to forty-eight parts per thousand, and this gives an idea of the proportion of globules which are seen on microscopical ex- amination. There has been a great deal of discussiqn with regard to the anatomical constitution of the milk-globules. In many late works it is stated that they are true anatomical ele- ments, composed of fatty matters surrounded by an albumin- oid membrane; but other writers assume that the fat is merely in the form of an emulsion, and is simply divided into globules and held in suspension, like the fatty particles of the chyle. ~No one, however, has assumed to have seen the investing membrane of the milk-globules, and its exist- ence is only inferred from the behavior of these little par- ticles in the presence of certain reagents. It is unnecessary to review in detail the numerous opin- ions that have been advanced on this subject. As far as can be ascertained by simple examination, even with the highest magnifying powers., the globules appear perfectly MILK. 91 homogeneous ; and the burden of proof rests with those who profess to be able to demonstrate the existence of .an invest- ing membrane. Robin, one of the highest authorities on these subjects, argues against the existence of a membrane, and opposes the observations of those who assume to have demonstrated it by explanations of the phenomena produced by reagents, which do not involve, as a necessity, the pres- ence of such a structure. The arguments in favor of its ex- istence are not very satisfactory ; and the experiments upon which they are based relate chiefly to the action of ether upon the globules before and after the action of other reagents. If a quantity of milk be shaken up with an equal volume of ether, the mixture remains opaque ; but if a little potash be added, the fatty matters are dissolved, and the mixture then becomes more or less clear. These facts are all that can be observed without following out the changes with the microscope. Robin has shown that the fatty particles are acted upon when the milk is thoroughly agitated with ether alone ; and that the opacity is then due to the fact that the ether, with the fat in solution, is itself in the form of an emulsion. If the opaque mixture of milk and- ether be ex- amined with the microscope, globules are seen, larger than, the ordinary milk-globules, much paler, and possessing much less refractive power. These he supposes to be composed of fat and ether. If potash be added, either before or after the addition of ether, the constitution of the whole mass of liquid is changed, and it becomes somewhat transparent, though by no means perfectly clear.1 It is assumed that, in the first instance, the ether does not attack the globules, be- cause it has no effect upon the membrane which is supposed to exist, and that the potash acts upon the membrane, allow- ing the ether then to take up the fat ; but if the observations of Robin be correct, it is evident that this view cannot be sustained. If dilute acetic acid be added to a specimen of milk under 1 ROBIN, Lemons sur les humeurs, Paris, 1867, p. 399, et seq. 92 SECRETION. the microscope, the globules become deformed, and some of them show a tendency to run together ; an appearance which is supposed by Henle, who was the first to study closely the action of acetic acid upon the milk-globules, to indicate the existence of a membrane.1 This deduction, however, is not justifiable. Acetic acid readily coagulates the caseine, a principle which is most efficient in maintaining the fat in its peculiar condition. The coagulating caseine then presses upon the globules, and produces, in this way, all the changes in form that have been observed. Most of the other arguments in favor of the existence of a membrane have no support in direct observation, and con- sequently do not demand special consideration ; while all the facts which we have been able to find relating to this sub- ject go to show that the fatty matters in the milk are in the condition of a simple emulsion. The precise condition, however, of the fluid immediately surrounding the globules is not fully understood. Certain of the constituents of fluids capable of forming emulsive mixtures with liquid fats may form a coating of excessive tenuity immediately around the globules, but they never constitute distinct membranes ^capable of resisting the action of solvents upon the fats ; and, in the case of the milk, they do not prevent the mechanical union of the globules into masses, as occurs in the process of churning. Milk-globules less than -g-^Vo °f an mcn ^n diameter pre- sent under the microscope that peculiar oscillating motion known as the Brownian movement. This is arrested on the addition of acetic acid, by coagulation of the caseine. From these facts, it is evident that the milk-globules are composed simply of fat in the condition of a fine emulsion. They are not true anatomical elements, originating by a process of genesis in a blastema, undergoing physiological decay, and capable of self-regeneration from materials fur- nished by the menstruum in which they are suspended, like 1 HENLE, Traite d> anatomic generate, Paris, 1843, tome ii., p. 521. MILK. 93 the blood-corpuscles or leucocytes. They are simply ele- ments of secretion. Composition of the Milk. — "We do not propose, in treat- ing of the composition of the milk, to consider the various methods of analysis which have been employed by different chemists. The only constituent that has ever presented much difficulty in the estimation of its quantity is caseine ; but the various processes now employed in its extraction lead to nearly the same results. The following table, com- piled by Robin from the analyses of various chemists, gives the constituents of human milk.1 Composition of Human Milk. Water 902-717 to 863*149 Caseine (desiccated) 29*000 " 39*000 Lacto-proteine 1*000 " 2*770 Albumen traces " 0*880 ; Margarine 17*000 " 25*840 Oleine 7*500 " 11*400 Butyrine, Caprine, Caproi'ne, Ca- priline 0-500 " 0*760 ae, or lactose) 37*000 " 49'000 Lactate of soda (?) 0*420 " 0*450 Chloride of sodium 0*240 " 0*340 Chloride of potassium 1-440 " 1*830 Carbonate of soda 0*053 " 0'056 Carbonate of lime 0'069 " 0*070 Phosphate of lime of the bones 2'310 " 3'440 Phosphate of magnesia 0*420 " 0*640 Phosphate of soda 0*225 " 0*230 Phosphate of iron (?) 0*032 " 0*070 Sulphate of soda 0*074 " 0*075 Sulphate of potassa traces. 1,000*000 1,000*000 f Oxygen 1*29 \ Gases in solution -] Nitrogen 12*17 !• 30 parts per 1,000 in volume.2 ( Carbonic acid 16*54 ) 1 ROBIN, Le$ons sur les humeurs, Paris, 1867, p. 395. In copying this table, the arrangement has been somewhat modified, and an evident arithmetical error has been corrected. 3 HOPPE, Untersuchungen iiber die Bestandtheile der Milch und ihre nachsten I Butter, 25 to 38 «j ] 94: SECRETION. The proportion of water in milk is subject to a certain amount of variation, but this is not so considerable as might be expected from the great variations in the entire quantity of the secretion. In treating of the quantity of milk in the twenty-four hours, we have seen that the influence of drinks, even when nothing but pure water has been taken, is very marked ; and although the activity of the secretion is much increased by fluid ingesta, the quality of the milk is not usually aifected, and the proportion of water to the solid matters remains about the same. Nitrogenized Constituents of Milk. — Very little remains to be said concerning the nitrogenized constituents of human milk after what has been stated with regard to the compo- sition of cow's milk, in another volume.1 The different principles of this class undoubtedly have the same nutritive function, and appear to be identical in all varieties of milk, the only difference being in their relative proportion. It is a matter of common experience, indeed, that the milk of many of the lower animals will take the place of human milk, when prepared so as to make the proportions of its different constituents approximate the composition of the natural food of the child. A comparison of the composi- tion of human milk and cow's milk shows that the former is poorer in nitrogenized matters, and richer in butter and sugar ; and consequently, the upper strata of cow's milk, appropriately sweetened and diluted with water, very nearly represent the ordinary breast-milk. Caseine is by far the most important of the nitrogenized principles of milk, and supplies nearly all of this kind of Zerstzungen. — VIRCHOW'S Archiv, Berlin, 1859, Bd. xvii., S. 439. The observa- tions of Hoppe were made upon goat's milk, and in the apparatus used, the milk was drawn directly into the receiver and carefully protected from contact with the air. Hoppe criticises the observations of Lehmann and Vogel as probably incorrect, the fluid not being sufficiently protected from the atmosphere, which gives, according to Hoppe, an excess in the proportion of oxygen. 1 Sec vol. ii., Alimentation, p. 77, et seq. MILK. 95 nutritive matter demanded by the child. Lacto-proteine,1 a principle described by Millon and Commaille, is not so well defined, and albumen exists in the milk in very small quan- tity. That albumen always exists in milk can readily be shown by the following process described by Bernard : If milk, treated with an excess of sulphate of magnesia so as to form a thin paste, be thrown upon a filter, the caseine and fatty matters will be retained, and the clear liquid that passes through shows a marked opacity upon the ap- plication of heat or the addition of nitric acid.2 The coagulation of milk depends upon the reduction of the caseine from a liquid to a semisolid condition. ^Vhen milk is allowed to coagulate spontaneously, or sour, the change is effected by the action of the lactic acid which re- sults from a transformation of a portion of the sugar of milk. Caseine, in fact, is coagulated by any of the acids, even the feeble acids of organic origin. It differs from albumen in this regard, and in the fact that it is not coagulated by heat. It has been suggested that in fresh milk the caseine exists in combination with carbonate of soda, and that coagulation always takes place from the action of acids upon this salt, by which the caseine is set free. It is true that coagulated caseine may be readily dissolved in a solution of carbonate of soda, but it has been shown by the experiments of Selmi, that coagulation may be induced by the agency of certain neutral principles, while the milk retains its alkaline reac- tion. If fresh milk be slightly raised in temperature, and be treated with an infusion of the gastric mucous membrane of the calf, coagulation will take place in from five to ten minutes, the clear liquid still retaining its alkaline reaction.8 This observation has been repeatedly confirmed. Simon 1 MILLOX ET COMMAILLE, Nouvdle substance albumio'ide contenue dans le lait. — Cornptes rcndus, Paris, 1864, tome lix., p. 301. 2 BERNARD, Liquides de rorganisme, Paris, 1859, tome ii., p. 224. 3 SELMI, RecJierches sur faction de la prtsure dans la coagulation du lait, — Journal de pharmacie et de chimie, Paris, 1846, 3me serie, tome ix., p. 265. 96 SECRETION. has also found that the mucous membrane of .the stomach of an infant a few days old, that had recently died, coagu- lated woman's milk more readily than the mucous membrane of the stomach of the calf.1 Non-Nitrogenized Constituents of Milk. — Non-nitro- genized matters exist in abundance in the milk. The liquid caseine and the water hold the fats, as we have seen, in the condition of a fine and permanent emulsion. This fat has been separated from the milk and analyzed by chemists, and is known under the name of butter. In human milk, the butter is much softer than in the milk of many of the inferior animals, particularly the cow ; but it is composed of essentially the same constituents, though in different proportions. In different animals there are de- veloped, even after the discharge of the milk, certain odor- ous principles, more or less characteristic of the animal from which the butter is taken. The greatest part of the butter consists of margarine. It contains, in addition, oleine, with a small quantity of peculiar fats, not very well determined, called butyrine, caprine, caproine, and capriline. The margarine and oleine are principles found in the fat throughout the body ; but the last-named substances are peculiar to the milk. These are especially liable to acidification, and the acids resulting from their decomposition give the peculiar odor and flavor to rancid butter.3 Bromeis estimated the differ- ent constituents of the butter from cow's milk, and found it to contain sixty-eight parts of margarine, thirty parts of oleine, and two parts of butyrine, capronine, and caprine.3 1 SIMON, Animal Chemistry with Reference to the Physiology and Pathology of Han, Philadelphia, 1846, p. 333. 2 Butyrine was discovered, and the changes which it is liable to undergo were first described by Chevreul. (Faite pour servir d Vhistoire du beurre de vache. Extraits d'un memoire lu d VAcademie des Sciences, le 14 juin, 1819. — Annales de chimie et de physique, Paris, 1823, tome xxii., p. 373.) 8 BROMEIS, Ueber die in der Butter enthaltenen Fette und fetten Sauren. — An~ HULK. 97 Sugar of milk, sometimes called lactine, or lactose, is the most abundant of the solid constituents of the mammary secretion. It is this principle that gives to the milk its peculiar sweetish taste, though this variety of sugar is much less sweet than cane-sugar. The chief peculiarities of milk- sugar are, that it readily undergoes change into lactic acid in the presence of nitrogenized ferments, and takes on .alco- holic fermentation slowly and with difficulty. At one time, indeed, it was supposed that milk-sugar could not be decom- posed into alcohol and carbonic acid; but it is now well established that this change can be induced, the only pecu- liarity being that it takes place very slowly. In some parts of the world, intoxicating drinks are made by the alcoholic fermentation of milk. Milk-sugar is composed of CiaHwOia and responds to the ordinary tests for the animal varieties of sugar. A consideration of the nutritive action of the fatty and saccharine constituents of milk belongs properly to the sub- jects of alimentation and nutrition. It may be stated here, however, that these principles seem to be as necessary to the nutrition of the child as the nitrogenized principles ; though the precise manner in which they affect the development and regeneration of the tissues has not been ascertained. Inorganic Constituents of Milk. — It is probable that many inorganic principles exist in the milk which are not given in the table ; and the separation of these principles from their combinations with organic matters is one of the most difficult problems in physiological chemistry. This must be the case, for during the first months of extra-uterine nalen der Chemie und Pharmatie, Heidelberg, 1842, B. xlii., S. 70. The above is an approximative estimate of the proportions of the various fatty constituents of butter, deduced from the quantities of fatty acids 'obtained. Bromeis, like many chemists of that day, supposed that the neutral fats were composed of the fatty acids combined with glycerine, or the oxide of glycile. It is now gen- erally admitted that the fatty acids and glycerine are formed by actual decom- position, and do not exist in combination in the neutral fats. V 98 SECEETION. existence, the child derives all the inorganic, as well as the organic matters necessary to nutrition and development, from the breast of the mother. The reaction of the milk depends upon the presence of the alkaline carbonates, and these principles are important in preserving the fluidity of the caseine. It is not determined precisely in what form iron exists in the milk, but its presence here is undoubted. A comparison of the composition of the milk with that of the blood will show that most of the important in- organic principles found in the latter fluid exist also in the milk. Hoppe has indicated the presence of carbonic acid, nitro- gen, and oxygen, in solution, in milk.1 Of these gases, car- bonic acid is the most abundant. It is well known that the presence of gases in solution in liquids renders them more agreeable to the taste, and carbonic acid increases very ma- terially their solvent properties. Aside from these considera- tions, the precise function of the gaseous constituents of the milk is not apparent. A study of the composition of the milk fully confirms the fact, which we have already had occasion to state, that this is a typical alimentary fluid, and presents in itself the proper proportion and variety of material for the nourish- ment of the body during the period when the development of the system is going on with its maximum of activity. The form in which its different nutritive constituents exist is such that they are easily digested and are assimilated with great rapidity. Variations in the Composition of the Milk. The most elaborate researches concerning the variations in the composition of the milk are those of Yernois and Becquerel. Their observations relate to the composition of milk both in health and disease ; but we shall consider 1 Loc. dt. MILK. 99 only the differences this fluid has been found to present under varying normal conditions. Yernois and Becquerel have in- dicated a certain amount of variation at different ages and at different periods in lactation, but they show, at the same time, that the fluid is not subject to changes in its composition suf- ficiently great to influence materially the nutrition of the child. * If the composition of the milk be compared at different periods of lactation, it will be found to undergo great changes during the first few days. In fact, the first fluid secreted after parturition is so different from other milk, that it has been called by another name. It is then known as colostrum, the peculiar properties of which will be con- sidered more fully hereafter under a distinct head. As the secretion of milk becomes established, the fluid, from the first to the fifteenth day, becomes gradually diminished in density and in its proportion of water and of sugar, while there is a progressive increase in the proportion of most of the other constituents ; viz., butter, caseine, and the inor- ganic salts.1 The milk, therefore, as far as we can judge from its composition, as it increases in quantity during the first few days of lactation, is constantly increasing in its nutritive properties. The differences in the composition of the milk, taken from month to month during the entire period of lactation, are not so distinctly marked. It is difficult, indeed, to indicate any constant variations of sufficient importance to lead to the view that the milk varies much in its nutritive properties at different times, within the ordinary period of lactation. If we except the first few months, the secretion is not found to present any constant variations in density. Yernois and Becquerel found a notable increase in the proportion of solid matters from the first to the third month ; the sugar was increased from the eighth to the tenth month ; the ca- 1 YERNOIS ET BECQUEREL, Du lait ckez lafemme, Paris, 1853, p. 24. 100 SECRETION. seine was increased from the first day to the second month, inclusive, and diminished from the tenth to the twenty- fourth month ; there was a constant and considerable increase in the proportion of butter, from the first day to the fifth month, and a diminution from the fifth to the sixth, and from the tenth to the eleventh month ; there was a slight, feeble, but almost constant and progressive increase in the proportion of salts from the first day to the fifth month, and a diminution at all other periods.1 The differences noted between the milk of primiparse and multiparse were very slight and not very important. As a rule, however, the milk of primiparae approached more nearly the normal standard. The menstrual periods, when they occur during lactation, have been found by most observers to modify considerably the composition and properties of the milk ; and it is well known to practical physicians that the secretion is then liable to produce serious disturbances of the digestive system of the child, though frequently these effects are not observed. The changes in the composition of the milk which com- monly occur during menstruation are, great increase in the quantity of caseine, increase in the proportion of butter and the inorganic salts, and a slight diminution in the propor- tion of sugar. The common impression that the milk is unfit for the nourishment of the child if pregnancy occur during lactation is undoubtedly well-founded, though analy- ses of the milk of pregnant women have never been made on an extended scale. Yernois and Becquerel made but one examination of this kind, at the third month of gesta- tion, and found a great increase in the proportion of butter, slight increase in sugar and the inorganic salts, and a slight diminution in the proportion of caseine.2 The question is frequently discussed by physiological writers, whether the milk of fair women is different from that of brunettes. There are hardly sufficient data, however, 1 Op. tit., p. 31. 2 Op. tit., p. 38. MILK. 101 to form a definite opinion upon this subject. The analyses of L'Heritier,1 and Yernois and Becquerel,8 indicate a greater proportion of most of the solid matters in the milk of brunettes, with a very slight difference in the proportion of butter in favor of blondes. Almost all authorities who have expressed an opinion upon this question give the preference to the milk of brunettes. Donne, however, expresses him- self very decidedly against the popular prejudice in favor of brunettes as nurses. " As regards the color of the skin and the hair, the results at which I have arrived in nowise jus- tify the generally-received popular prejudice in favor of brunettes ; in more than four hundred nurses, I found no sensible difference in favor of brunettes over blonde women or over those with chestnut hair; but of nine red-haired women, five only presented the proper qualities."' It would be interesting in this connection to determine wheth- er there be any marked difference in the milk of the black and the white race, particularly as it has long been the cus- tom in some parts of the United States to permit white children to be nursed by black women. Infants that are nourished in this way apparently thrive as well as those nursed by white women; and there is no reason to sup- pose that there is any difference in the milk of the two races. Sir Astley Cooper mentions some interesting facts concerning the black women of the West Indies, communi- cated to him by his nephew, Dr. Young, which show that 1 L'HERITIER, TraitS de chimie pathologique, Paris, 1842, p. 638; YERXOIS ET BECQUEREL, op. cit., p. 52. 2 L'Heritier was the first to compare critically the milk of blondes with that of brunettes. In two women, twenty-two years of age, and subjected to the same regimen, the milk of the brunette contained much more caserne, butter, sugar, and salts, than the milk of the blonde ; but these two instances presented the ex- tremes of difference ; and as the mean of all his observations, it was found that the difference was comparatively slight. Yernois and Becquerel arrived at es- sentially the same results, except that the proportion of butter was a little greater in the milk of fair women. 3 DOXXE, Cours de microscopic, Paris, 1844, p. 409. 102 SECRETION. there is probably no difference between the milk of the blacks and of Europeans.1 In normal lactation, there is no marked and constant dif- ference in the composition of milk that has been secreted in great abundance, and milk which is produced in compara- tively small quantity ; nor do we observe that difference be- tween the milk first drawn from the breast and that taken when the ducts are nearly empty, which is observed in the milk of the cow.2 The influence of alimentation and the taking of liquids upon lactation relate chiefly to the quantity of milk, and have already been considered.8 In treating of the influences which modify the secretion of milk, we have already alluded to the effects of violent mental emotions upon the production and the composition of this fluid. The very remarkable case of profound alteration of the milk by violent grief, detailed by Yernois and Bec- querel, is the only one in which the secretion in this condi- tion has been carefully analyzed. The changes thus pro- duced in its composition have already been referred to,4 the most marked difference being observed in the proportion of butter, which became reduced from 23*79 to 5*14 parts per 1,000. Colostrum. Near the end of utero-gestation, during a period which varies considerably in different women and has not been ac- curately determined, a small quantity of a thickish, stringy fluid may frequently be drawn from the mammary glands. This bears little resemblance to perfectly-formed milk. It is small in quantity, and is usually more abundant in multi- part than in primiparae. This fluid, with that secreted for 1 COOPER, The Anatomy and Diseases of the Breast, Philadelphia, 1845, p. 103, et seq. 2 See vol. ii., Alimentation, p. 79. 3 See page 83. 4 See page 86. COLOSTRUM. 103 the first few days after delivery, is called colostrum. It is yellowish, semiopaque, of a distinctly alkaline reaction, and somewhat mucilaginous in its consistence. Its specific gravi- ty is considerably above that of the ordinary milk, being from 1040 to 1060. As lactation progresses, the character of the secretion rapidly changes, until it becomes loaded with true milk-globules and assumes the characters of ordinary milk. The opacity of the colostrum is due to the presence 'of a number of different corpuscular elements. Milk-globules, very variable in size and number, are to be found in the secretion from the first. These, however, do not exist in sufficient quantity to render the fluid very opaque, and they are frequently aggregated in rounded and irregular masses, held together, apparently, by some glutinous matter. Pecu- liar corpuscles, first accurately described by Donne, un- der the name of " granular bodies," and supposed to be characteristic of the colostrum, always exist in this fluid.1 These are now known as colostrum-corpuscles. They are spherical, varying in size from 2^Qd to -g-^j- of an inch, are sometimes pale, but more frequently quite granular, and contain very often a large number of fatty particles. They behave in all respects like leucocytes, and are described by Eobin as a variety of these bodies.3 Many of them are pre- cisely like the leucocytes found in the blood, lymph, or pus. Their appearance was very well described by Donne, who supposed that they were mucus-corpuscles.3 We now know, however, that the so-called mucus-corpuscle does not differ from the pus-corpuscle or the white corpuscle of the blood ; and leucocytes generally, when confined in liquids that are not subject to movements, are apt to undergo enlargement, to become fatty, and, in short, present all the different ap- pearances observed in the colostrum-corpuscles. In addition 1 DONNE, Cours de microscopic, Paris, 1844, p. 400. 2 ROBIN, Sur quelques points de ranatomie et de la physiologic deft leucocytes.— Journal de la physiologic, Paris, 1859, tome ii., p. 56. 8 DONNE, loc. dt. 104 SECRETION. to these corpuscular elements, a small quantity of mucosine may frequently be observed in the colostrum, on microscopi- cal examination. On the addition of ether to a specimen of colostrum under the microscope, most of the fatty particles, both within and without the colostrum-corpuscles, are dissolved. Am- monia added to the fluid renders it stringy, and sometimes the entire mass assumes a gelatinous consistence. In its proximate composition, the colostrum presents many points of difference from true milk. It is sweeter to the taste, and contains a greater proportion of sugar and of the inorganic salts. The proportion of fat is at least equal to the proportion in the milk, and is generally greater. In- stead of caseine, the pure colostrum contains a large propor- tion of albumen; and as the character of the secretion changes in the process of lactation, the albumen becomes gradually reduced in quantity and caseine takes its place. Without referring in detail to the numerous analyses of colostrum in the human subject and in the inferior animals, by Simon, Lassaigne, and others, the following, deduced from the analyses of Clemm, may be taken as the ordinary composition of this fluid in the human female : Composition of the Colostrum.1 Water 945'24 to 851-97 Albumen 29*81 " 80'73 Butter 7-07" 41'30 Sugarofmilk 17'27 " 43*69 Chloride of sodium 0'51 "j Chloride of potassium 1'25 Phosphates and sulphates of potassa, of lime, > 4*41 " 5*44 and of magnesia 2-96 Phosphate of iron O'Ol J Colostrum ordinarily decomposes much more readily than milk, and takes on putrefactive changes very rapidly. If it be allowed to stand for from twelve to twenty-four hours, it sep- 1 ROBIN, Lemons sur les humeurs, Paris, 1867, p. 409. COLOSTRUM. 105 arates into a thick, opaque, yellowish cream and a serous fluid. In an observation by Sir Astley Cooper, nine meas- ures of colostrum, taken soon after parturition, after twenty- four hours of repose, gave six parts of cream to three of milk.1 The peculiar constitution of the colostrum, particularly the presence of an excess of sugar and inorganic salts, renders it somewhat laxative in its effects, and it is supposed to be useful, during the first few days after delivery, in as- sisting to relieve the infant of the accumulation of meconium- As the quantity of colostrum that may be pressed from the mammary glands during the latter periods of utero- gestation, particularly the last month, is very variable, it becomes an interesting and important question to determine whether this secretion have any relation to* the quantity of milk that may be expected after delivery. This has been made the subject of careful study by Donne, who arrived at the following important conclusions : In women in whom the secretion of colostrum is almost absent, the fluid being in exceedingly small quantity, viscid, and containing hardly any corpuscular elements, there is hardly any milk produced after delivery. In women who, before delivery, present a moderate quan- tity of colostrum, containing very few milk-globules and a number of colostrum-corpuscles, after delivery the milk will be scanty or it may be abundant, but it is always of poor quality. But when the quantity of colostrum produced is con- siderable, the secretion being quite fluid and rich in corpus- cular elements, particularly milk-globules, the milk after delivery is always abundant and of good quality.3 From these observations it would seem that the produc- tion of colostrum is an indication of the proper development of the mammary glands ; and the early production of fatty 1 COOPER, The Anatomy and Diseases of the Breast, Philadelphia, 1845, p. 85. 0 DONNE, op. cit., p. 407, et seq. 106 SECRETION. granules, which are first formed by the cells lining the se- creting vesicles, indicates the probable activity in the secre- tion of milk after lactation has become fully established. The secretion of the mammary glands preserves the char- acters of colostrum until toward the end of the milk-fever, when the colostrum-corpuscles rapidly disappear, and the milk-globules become more numerous, regular, and uniform in size. It may be stated in general terms that the secretion of milk becomes fully established and all the characters of the colostrum disappear from the eighth to the tenth day after delivery. A few colostrum-corpuscles and masses of agglutinated milk-globules may sometimes be discovered after the tenth day, but they are very rare ; and after the fif- teenth day the milk does not sensibly change in its micro- scopical or its chpmical characters. Lacteal Secretion in the Newly-Born. It is a curious fact that in infants of both sexes there is generally a certain amount of secretion from the mammary glands, commencing at birth, or from two to three days after, and continuing sometimes for two or three weeks. The quantity of fluid that may be pressed out at the nipples at this time is very variable. Sometimes only a few drops can be obtained, but occasionally the fluid amounts to one or two drachms. Although it is impossible to indicate the object of this secretion, which takes place when the glands are in a rudimentary condition, it has been so often observed and described by physiologists that there can be no doubt with regard to the nature of the fluid, and the fact that the secretion is almost always produced in greater or less quan- tity. The latest researches upon this subject are those of Gub- ler and Quevenne, who have given a tolerably complete analysis of the fluid. The fact of the almost constant oc- currence of the secretion was fully established, in 1853, by MILK OF THE IXFANT. 107 Guillot.1 The following is an analysis by Quevenne of the secretion obtained by Gubler. The observations of Gubler were very extended, and were made upon about twelve hun- dred children. The secretion rarely continued more than four weeks, but in four instances it persisted for two months." Composition of the Mttk of the Infant. Water 894'00 Caseine 26'40 Sugar of milk 62*20 Butter 14*00 Earthy phosphates 1-20 Soluble salts (with a small quantity of insoluble phosphates) . 2*20 1,000-00 This fluid does not differ much in its composition from ordinary milk. The proportion of butter is much less, but the amount of sugar is greater, and the quantity of caseine is nearly the same. Of the other fluids which are enumerated in the list of secretions, the saliva, gastric juice, pancreatic juice, and the intestinal fluids have already been considered in connec- tion with digestion.3 The physiology of the lachrymal se- cretion will be taken up in connection with the eye, and the bile will be treated of fully under the head of excretion. 1 GUILLOT, De la secretion du lait chez leg enfants nouveau-nes, et dts accidents qui peuvent faccompagner. — Archives generales, Paris, 1853, ome serie, tome iL, p. 513, et seq. • GUBLER, Jfemoire sur la secretion et la composition du lait chez les enfants nouveau-nes des deux sexes. — Comptes rendus et memoires de la Societe de Biologie, annee, 1855, Paris, 1856, p. 289. 3 See vol. ii., Digestion. CHAPTER IY. EXCRETION ACTION OF THE SKIN. Differences between the secretions proper and the excretions — Composition of the excretions — Mode of production of the excretions — Discharge of the excretions — Physiological anatomy of the skin — Extent and thickness of the skin — Layers of the skin — The corium, or true skin — The epidermis and its appendages — Desquamation of the epidermis — Physiological anat- omy and uses of the nails and hair — Development and growth of the nails — Varieties of hair — Number of the hairs — Roots of the hairs, and hair-fol- licles— Structure of the hairs — Sudden blanching of the hair — Uses of the hairs — Perspiration — Sudoriparous glands — Mechanism of the secretion of sweat — Quantity of cutaneous exhalation — Properties and composition of the sweat — Peculiarities of the sweat in certain parts. IN entering upon the study of the elimination of effete matters, it is necessary to appreciate fully the broad distinc- tions between the secretions proper and the excretions, in their composition, the mechanism of their production, and their destination. These considerations are again referred to,1 for the reason that they have not ordinarily received that attention in works upon physiology which their impor- tance demands. The mechanism of excretion is insepara- bly connected with the function of nutrition, and forms one of the great starting-points in the study of all the modifica- tions of nutrition in diseased conditions. Taking the urine as the type of the excrementitious fluids, it is found to contain none of those principles included in the class of non-crystallizable, organic nitrogenized mat- ters, but is composed entirely of crystallizable matters simply 1 See chapter I. on " Secretion in General." GENERAL CONSIDERATIONS. 109 held in solution in water. The character of these principles depends upon the constitution of the blood and the general condition of nutrition, and not upon any formative action in the glands. The principles themselves represent the ulti- mate physiological changes of certain constituent parts of the living organism, and are in such a condition that they are of no further use in the economy and are simply dis- charged from the body. Certain inorganic matters are found in the excrementitious fluids, are discharged with the products of excretion, and are thus associated with the organic principles of the economy in their physiological de- struction, as well as in their deposition in the tissues. Co- agulable organic matters, such as albumen or fibrin, never exist in the excrementitious fluids under normal conditions ; except as the products of other glands may become acciden- tally or constantly mixed with the excrementitious fluids proper. The same remark applies to the non-nitrogenized matters (sugars and fats), which, whether formed in the organism or taken as food, are consumed as such in the pro- cess of nutrition. The production of the excretions is con- stant, being subject only to certain modifications in activity, dependent upon varying conditions of the system. All of the elements of excretion preexist in the blood, either in the precise condition in which they are discharged, or in some slightly modified form. Under the head of excretion, it is proposed to consider the general properties and composition of the different ex- crementitious fluids ; but the relations of the excrementitious matters themselves to the tissues will be more fully treated of in connection with nutrition. The urine is a purely excrementitious fluid. The perspi- ration and the secretion of the axillary glands are excre- mentitious fluids, but contain a certain amount of the secre- tion of the sebaceous glands. Certain excrementitious matters are found in the bile, but at the same time, this fluid contains principles manufactured in the liver, and has 1 10 EXCRETION. an important function as a secretion, in connection with the process of digestion. Physiological Anatomy of the Skin. The skin is one of the most complex and important structures in the body, and possesses a variety of functions. In the first place it forms a protective covering for the gen- eral surface. It is quite thick over the parts most subject to pressure and friction, is elastic over movable parts and those liable to variations in size, and in many situations is covered with hair, which affords an additional protection to the sub- jacent structures. The skin and its appendages are bad conductors of caloric, are capable of resisting very consider- able variations in temperature, and thus tend to maintain the normal standard of the animal heat. As an organ of tactile sensibility, the skin has an important function, being abundantly supplied with sensitive nerves, some of which present an arrangement peculiarly adapted to the nice ap- preciation of external impressions. The skin assists in pre- serving the external forms of the muscles ; it relieves the abrupt projections and depressions of the general surface, and gives roundness and grace to the contours of the body. In some parts it is very closely attached to the subjacent struc- tures, while in others it is less adherent, and is provided with a layer of adipose tissue. As an organ of excretion, the skin is very important ; and although the quantity of excrementitious matter exhaled from it is not very great, and probably not subject to much varia- tion, the evaporation of water from the general surface is always considerable, and is subject to such modifications as may become necessary from the varied conditions of the ani- mal temperature. Thus, while the skin protects the body from external influences, its function is important in regu- lating the heat produced as one of the numerous phenomena attendant upon the general process of nutrition. ANATOMY OF THE SKIN. Ill As the skin presents such a variety of functions, its physiological anatomy is most conveniently considered in connection with different divisions of the subject of physi- ology. For example, under the head of secretion, we have already taken up the structure of the different varieties of sebaceous glands. The anatomy of the skin as an organ of touch will be most appropriately considered in connection with the nervous system. In this connection we will describe the excreting organs found in the skin ; and here it will be most convenient to study briefly its general structure and the most important points in the anatomy of the epidermic ap- pendages. A full and connected description of the skin and its appendages belongs properly to works upon anatomy. General Appearance of the Skin. — It is unnecessary to discuss very minutely the general appearance of the skin. Its color is sufficiently familiar. The tissue of the true skin is whitish and semitransparent, so that the color of the sub- jacent parts gives to it a peculiar tint. The blood contained in its vessels, as is well known, is capable of modifying greatly the color of the general surface. The deep layer of the epidermis always contains more or less pigmentary mat- ter, which gives the colors characteristic of different races, and produces the variations in complexion that are observed in different individuals of the same race. The pigment, in the white races, is but slightly developed at birth, but in- creases in quantity with age. The general surface, with the exception of the palms of the hands and the soles of the feet, is covered with hairs, which are very largely developed in certain situations. The furrows and folds of the skin are produced either by the con- traction of the subjacent muscles ; by a loss of elasticity in the skin, as in old age ; by an excessive development of fat in certain parts ; or by the movements of the joints. Faint, irregular lines are observed on the surface in most parts j but upon the palms of the hands and the soles of the feet these 112 EXCRETION. are well marked and regular, particularly upon the palmar surfaces of the last phalanges, where they are in the form of concentric curves, so easily observed with the naked eye that further description is unnecessary. These lines are formed by the more or less regular arrangement of the papil- lae of the true skin. Extent and Thickness of the Skin. — Sappey has made a number of very careful observations upon the extent of the surface of the skin. Without detailing the measurements of different parts, it may be stated, as the general result of his observations, that the cutaneous surface in a good-sized man is equal to about twelve square feet ; and in men of more than ordinary size it may extend to fourteen, fifteen, or even eighteen square feet. In men of medium size, in France, the surface does not exceed ten square feet ; and in women, it is ordinarily from six to eight.1 When we con- sider the great extent of the cutaneous surface, it is not sur- prising that the amount of secretion, under certain conditions, should be enormous. Indeed, under all circumstances, the amount of elimination is very considerable, and the skin is really one of the most important of the glandular structures. The thickness of the skin varies very much in different parts. Where it is naturally exposed to constant pressure and friction, as on the soles of the feet or the palms of the hands, the epidermis becomes very much thickened, and in this way the more delicate structure of the true skin is pro- tected. It is well known that the development of the epi- dermis, under these conditions, varies in different persons, with the amount of pressure and friction to which the sur- face is habitually subjected. The true skin is from -^ to $ of an inch in thickness ; but in certain parts, particularly the external auditory meatus, the lips, and the glans penis, it frequently measures not more than y^- of an inch.2 1 SAPPEY, Traite d' anatomic descriptive, Paris, 1852, tome ii., p. 447. 2 POUCHET, Precis d'histologie humaine, Paris, 1864, p. 329. ANATOMY OF THE SKIN. 113 Layers of the Skin. — The skin is naturally divided into two principal layers, which may be readily separated from each other by maceration. These are, the true skin (cutis vera, derma, or corium), and the epidermis, cuticle, or scarf- skin. The true skin is attached to the subjacent structures, more or less closely, by a fibrous structure called the sub- cutaneous areolar tissue, in the meshes of which we com- monly find a certain quantity of fatty tissue. This layer is sometimes described under the name of the panniculus- adiposus. The thickness of the adipose layer varies very much in different parts of the general surface and in differ- ent persons. There is no fat beneath the skin of the eyelids, the upper and outer part of the ear, the penis, and the scro- tum. Beneath the skin of the cranium, the nose, the neck, and the dorsum of the hand and foot, the knee and the elbow, the fatty layer is about -£% of an inch in thickness. In other parts it usually measures from ^ to ^ of an inch.1 In very fat persons it may measure one inch or more. Upon the head and the neck, in the human subject, are muscles at- tached more or less closely to the skin. These are capable of moving the skin to a slight extent. Muscles of this kind are largely developed and quite extensively distributed in some of the lower animals. There is no sharply-defined line of demarcation between the cutis and the subcutaneous areolar tissue ; and the under surface of the skin is always irregular, from the presence of numerous fibres which are necessarily divided in detaching it from the subjacent structures. The fibres which enter into the composition of the skin near its under surface become looser in their arrangement, the change taking place rather abruptly, until they present large alveolae, which generally contain a certain amount of adipose tissue. The layer called the true skin is subdivided into a deep, reticulated, or fibrous layer, and a superficial portion, called 1 KRAUSE, in WAGNER'S Handucdrterbuch der Physiologic, Braunschweig, 1844, Bd. ii., S. 116. 8 .114 EXCRETION. the papillary layer. The epidermis is also divided into two layers ; an external layer, called the horny layer ; and an in- ternal layer, called the Malpighian, or the mucous layer, which is in contact with the papillary layer of the corium. The Cerium, or True Skin. — The reticulated and the papillary layer of the true skin are quite distinct. The lower stratum, the reticulated, is much thicker than the papillary layer, is dense, resisting, quite elastic, and slightly contractile. It is composed of numerous bundles of white fibrous tissue interlacing with each other in every direction, generally at acute angles. Distributed throughout this layer are found numerous anastomosing elastic fibres of the small variety, and with them a number of non-striated muscular fibres. This portion of the skin contains, in addition, a con- siderable quantity of amorphous matter which serves to hold the fibres together. The muscular fibres are particularly abundant about the hair-follicles and the sebaceous glands connected with them, and their arrangement is such, that when they are excited to contraction by cold or by electrici- ty, the follicles are drawn up, projecting upon the general surface, and producing the appearance known as " goose- flesh." Contraction of these fibres is particularly marked about the nipple, producing the so-called erection of this organ, and about the scrotum and penis, wrinkling the skin of these parts. The peculiar arrangement of the little muscles around the hair-follicles, forming little bands at- tached to the surface of the true skin and the base of the follicles, was first described by Kolliker,1 and explains fully the manner in which the " goose-flesh " is produced. Con- traction of the skin, in obedience to the stimulus of electrici- ty, has been demonstrated by Froriep, Brown-Sequard, and Kolliker, both in the living subject and in executed criminals immediately after death.3 1 KOLLIKER, Handbuch der Gewebelelire des Memclien, Leipzig, 1867, S. 98. 8 KOLLIKER, Manual of Human Microscopic Anatomy, London, 1860, p. 86. -ANATOMY OF THE SKIN. 115 The papillary layer of the skin passes insensibly into the subjacent structure and presents no well-marked line of division. It is composed chiefly of the same kind of amorphous matter that exists in the reticulated layer. The papillae themselves appear to be simply elevations of this amorphous matter, though they may contain a few fibres. In this layer we find a number of fibro-plastic nuclei with a few little corpuscular bodies called by Kobin, cytoblastions.1 As regards their form, the papillae may be divided into two varieties ; the simple and the compound. The simple papillae are conical, rounded, or club-shaped elevations of the amorphous matter, and are irregularly distributed on the general surface. The smallest are from -^ to ^^j- of an inch in length, and are found chiefly upon the face. The largest are on the palms of the hands, the soles of the feet, and the nipple. These measure from -^j- to -^-5- of an inch. Large papillae, regularly arranged in a longitudinal direction, are found beneath the nails. The regular, curved lines observed upon the palms of the hands and the soles of the feet, particularly the palmar surfaces of the last phalanges, are formed by double rows of compound papillae, which pre- sent two, three, or four points attached to a single base. In the centre of each of these double rows of papillae is an ex- cessively fine and shallow groove, in which are found the ori- fices of the sudoriferous ducts. The papillae are abundantly supplied with blood-vessels, terminating in looped capillary plexuses, and nerves. The termination of the nerves is peculiar, and will be fully de- scribed in connection with the organs of touch. The ar- rangement of the lymphatics, which are very numerous in the skin, has already been indicated in the general descrip- tion of the lymphatic system.3 1 LITTRE ET ROBIN, Dictionnaire de medecine, Paris, 1865, Article, Cyto- blastion. 8 See vol. ii., Absorption, p. 430. 116 EXCRETION. The Epidermis and its Appendages. — The epidermis, or external layer of the skin, is a membrane composed ex- clusively of cells, containing neither blood-vessels, nerves, nor lymphatics. Its external surface is marked by exceed- ingly shallow grooves, which correspond to the deep furrows between the papillae of the derma. Its internal surface is applied directly to the papillary layer of the true skin, and follows closely all its inequalities. This portion of the skin is subdivided into two tolerably distinct layers. The in- ternal layer is called the rete mucosum, or the Malpighian layer, and the external is called the horny layer. . These two layers present certain important distinctive characters. The Malpighian layer is composed of a single stratum of prismoidal, nucleated cells, containing a greater or less amount of pigmentary matter, applied directly to all the inequalities of the derma, and a number of layers of rounded cells containing no pigment. The tipper layers of cells, with the scales of the horny layer, are semitransparent and nearly colorless ; and it is the pigmentary layer chiefly which gives to the skin its characteristic color and the peculiarities in the complexion of different races and of different individu- als. In the negro, this layer is nearly black ; and when the epi- dermis is removed, the true skin does not present any marked difference from the skin of the white race. All the epider- mic cells are somewhat colored in the dark races, but the upper layers contain no pigmentary granules. The cells of the pigmentary layer are *from 4 Q\ 6 to 3^0 of an inch in length, and from go1o0 to 4^d of an inch in their short diameter. The rounded cells in the upper layers are from 40100 to -g-oVu" of an inch in diameter. The absolute thickness of the rete mucosum is from 171OC) to -£$ of an inch. The horny layer is composed of numerous strata of hard, flattened cells, irregularly polygonal in shape, generally with- out nuclei, and measuring from -g-gVs- to ^^ of an inch in diameter. The deeper cells are thicker and more rounded than those of the superficial layers. NAILS AXD HAIR. 117 The epidermis serves as a protection to the more delicate structure of the true skin, and its thickness is proportionate to the exposure of the different parts. It is consequently much thicker upon the soles of the feet and the palms of the hands than in other portions of the general surface, and its thickness is very much increased in those who are habitually engaged in severe manual labor. Upon the face, the eyelids, and in the external auditory passages, the epidermis is' most delicate, measuring from -^J-g- to -^-J-^ of an inch in thickness. Upon the palm it is from -^ to -^ of an inch thick, and upon the sole of the foot it measures from -^ to -J of an inch.1 These variations depend entirely upon the development of the horny layer. The thickness of the rete mucosum, although it presents considerable variation in different parts, is rather more uniform. There is constantly more or less desquamation of the epi- dermis, particularly the horny layer, and the cells are regen- erated by a blastema exuded from the subjacent vascular parts. It is probable that there is a constant formation of cells in the deeper strata of the horny layer, which become flattened as they near the surface ; but there is no direct evidence that the cells of the rete mucosum undergo trans- formation into the hard, flattened scales of the horny layer. Physiological Anatomy and Uses of ike Nails and Sairs. — It is unnecessary, in this connection, to discuss very minutely the anatomy of the nails and hairs. They are or- dinarily regarded as appendages of the epidermis, produced by certain peculiar organs belonging to the true skin ; and an elaborate study of these parts belongs strictly to descrip- tive and general anatomy. To complete, however, the physiological history of the skin, it will be necessary to 1 KOLLIKER, Manual of Human Microscopical Anatomy, American Edition, Philadelphia, 1854, p. 146. Kolliker gives (he. cit.) accurate measurements of the epidermis in many different portions of the skin, to -which the reader is re- ferred for further information on this point. 118 EXCRETION. consider briefly the general arrangement of the cuticular appendages. The nails are situated on the dorsal surfaces of the distal phalanges of the fingers and toes. They serve to protect these parts, and in the fingers, are also quite important in prehension. The general appearance of the nails is so famil- iar that it requires no special description. In their study, anatomists have distinguished a root, a body, and a free border. The root is thin and soft, terminating in rather a jagged edge, which is turned slightly upward and is received into a fold of the skin extending around the nail to its free edge. The length of the root of course varies with the size of the nail, but it is generally from one fourth to one third of the length of the body. The body of the nail extends from the fold of skin which covers the root to the free border. This portion of the nail, with the root, is closely adherent by its under surface to the true skin. It is marked by fine but distinct longitudinal striae and very faint transverse lines. It is usually reddish in color, from the great vascularity of the subjacent structure. At the posterior part is a whitish portion of a semilunar shape, called the lunula, which has this appearance simply from the fact that the corium in this part is less vascular, and the papillae are not so regular as in the rest of the body. That portion of the skin situated beneath the root and the body of the nail is called the matrix. It presents highly vascular papillae, arranged in regular, longitudinal rows, and receives into its grooves corresponding ridges on the under surface of the nail. The free border of the nail begins at the point where the nail becomes detached from the skin. This is generally cut or worn away, and is constantly growing ; but if left to itself, it attains in time a definite length, which may be stated, in general terms, to be from an inch and a half to two inches. Examining the nail in a longitudinal section, the horny NAILS AST) HAIR. 119 layer, which is usually regarded as the true nail, is found to increase progressively in thickness from the root to near the free border. If the nail be examined in a transverse section, it will also be found much thicker in the central portion than near the edge, and that part which is received into the lateral portions of the fold becomes excessively thin like the rest of the root. The thickness of the true nail at the root is from -^-^ to -j-J-g- of an inch ; and, in the thickest por- tion of the body, it usually measures from ^ to -^ of an inch. The nail becomes somewhat thinner at and near the free border. Sections of the nails show that they are composed of two layers, which correspond to the Malpighian and the horny layer of the epidermis, though they are much more distinct. The Malpighian layer is applied directly to the ridges of the bed of the nail, and presents upon its upper surface ridges much less strongly marked than in the underlying true skin. This layer is rather thinner than the horny layer, is whitish in color, and is composed of numerous strata of elongated, prismoidal, nucleated cells, arranged perpendicularly to the matrix. These cells are from 3^0 to 17100 of an inch in length. The horny layer, which constitutes the true nail, is ap- plied by its under surface directly to the ridges of the Mal- pighian layer. It is dense and brittle, and composed of nu- merous strata of flattened cells, which cannot be isolated without the use of reagents. If the different strata of this portion of the nail be studied after boiling in a dilute solu- tion of soda or potash, it becomes evident that here, as in the horny layer of the epidermis, the lower cells are somewhat rouncjed, while those nearer the surface are flattened. These cells are nearly all nucleated, and measure from 10100 to -y^-g- of an inch in diameter. The thickness of this layer varies in different portions of the nail, while the Malpighian layer is nearly uniform. This layer is constantly growing, and con- stitutes the entire substance of the free borders of the nails. 120 EXCRETION. The connections of the nails with the true skin resemble those of the epidermis ; but the relations of these structures to the epidermis itself are somewhat peculiar. Up to the fourth month of foetal life, the epidermis covering the dorsal surfaces of the last phalanges of the fingers and toes does not present any marked peculiarities ; but at about the fourth month, the peculiar hard cells of the horny layer of the nails make their appearance between the Malpighian and the horny layer of the epidermis, and at the same time the Malpighian layer beneath this plate, which is destined to become the Malpighian layer of the nails, is somewhat thickened, and the cells assume more of an elongated form. The horny layer of the nails constantly thickens from this time ; but until the end of the fifth month, it is covered by the horny layer of the epidermis. After the fifth month, the epidermis breaks away and disappears from the sur- face ; and at the seventh month, the nails begin to increase in length. Thus, at one time, the nails are actually included between the two layers of the epidermis ; but after they have become developed, they are simply covered at their roots by a narrow border of the horny layer, the epidermis commencing again under the nail where the free border leaves the bed. The nails are therefore to be regarded as modifications of the horny layer of the epidermis, possessing certain anatomical and chemical peculiarities. The Malpig- Tbian layer of the nails is continuous with the same layer of the epidermis, but the horny layers are, as we have seen, distinct. One of the most striking peculiarities of the nails is in their mode of growth. The Malpighian layer is stationary, but the horny layer is constantly growing, if the nails be cut, from the root and bed. It is evident that the nails grow from the bed, as their thickness progressively increases in the body from the root to near the free border ; but their longitudinal growth is by far the more rapid. Indeed, the nails are constantly pushing forward, increasing in thickness NAILS AXD HATK. 121 as they advance. Xear the end of the body, as the horny layer becomes thinner, the growth from below is diminished. Hairs, varying greatly in size and development, cover nearly every portion of the surface of the body. The only parts in which they are not found are the palms of the hands and soles of the feet, the palmar surface of the fingers and toes, the dorsal surface of the last phalanges of the fin- gers and toes, the lips, the upper eyelids, the lining of the prepuce, and the glans penis. Some of the hairs are long, others are short and stiff, and others are fine and downy. These differences have led to a division of the hairs into three varieties. The first variety includes the long, soft hairs, which are found on the head, on the face in the adult male, around the genital organs and under the arms in both the male and the female, and sometimes upon the breast and over the general surface of the body and extremities, particularly in the male. The second variety, the short, stiff hairs, is found at the entrance of the nostrils, upon the edges of the eyelids, and upon the eyebrows. The third variety, the short, soft, downy hairs, are found on the general surface not occupied by the long hairs, and the caruncula lachrymalis. In early life, and ordinarily in the female at all ages, the trunk and extremities are covered with downy hairs ; but in the adult male, these frequently become developed into long, soft hairs. The hairs are usually set obliquely in the skin, and take a definite direction as they lie upon the surface. Upon the head and face, and, indeed, the entire surface of the body, the general course of the hairs may be followed out, and they present currents or sweeps that have nearly always the same direction. These " currents " have been carefully studied by Wilson, and are fully described in his work upon the healthy skin.1 1 WILSON, Healthy Skin, Philadelphia, 1854, p. 101, d seq. 122 EXCRETION. The diameter and length of the hairs are exceedingly vari- able in different persons, especially in the long, soft hairs of the head and beard. It may be stated in general terms that the long hairs attain the length of from twenty inches to three feet in women, and considerably less in men. There are instances, however, in women, in which the hair of the head measures considerably more than three feet, but these are quite unusual. Like the nails, the hair, when left ,to itself, attains in three or four years a definite length, but when it is habitually cut it grows constantly. The short, stiff hairs are from one quarter to one half an inch in length. The soft, downy hairs measure ordinarily from one twelfth to one half an inch. Hairs that have never been cut ter- minate in pointed extremities; and sometimes in hairs that have been cut, the ends become somewhat pointed, though they are never so sharp as in the new hairs. Of the long hairs, the finest are upon the head, where they average about ^J-g- of an inch in diameter, the extremes ordinarily being from -3-^5- to -g-J-g- of an inch for the finest, and from ^J-g- to yj^ of an inch for the coarsest. The hair is ordinarily coarser in women than in men. Dark hair is ordinarily coarser than light hair ; and upon the same head the extremes of variation are sometimes observed.1 The hairs of the beard and the long hairs of the body are coarser than the hairs of the head. Wilson estimates that the aver- age number of hairs upon a square inch of the scalp is about 1,000, and the number upon the entire head about 120,000. The short, stiff hairs are from -^-^ to yfg- of an inch in diameter, and the fine, downy hairs from 2o^00 to 1/00 of an inch. The variations in the color of the hairs in differ- ent races and in different individuals of the same race are sufficiently familiar. When the hairs are in a perfectly normal condition, they are very elastic, and may be stretched to from one fifth to one third more than their original length. Their strength 1 WILSON, op. cit., p. 84, et seq. NAILS AND HAIR. 123 varies with their thickness, but an ordinary hair from the head will bear a weight of six or seven ounces. A well- known property of the hair is that of becoming strongly electric by friction ; and this is particularly well marked when the weather is cold and dry. The electricity thus excited is negative. Sections of the shaft of the hairs show that they are oval, but their shape is very variable, straight hairs being nearly round, while curled hairs are quite flat. Another peculiarity of the hairs is that they are strongly hy- grometric. They readily absorb moisture and become sen- sibly elongated, a property which has been made use of by physicists in the construction of delicate hygrometers. Hoots of the Hairs and Hair -follicles. — The roots of the hairs are embedded in follicular openings in the skin, which differ in the different varieties only in the depth to which they penetrate the cutaneous structure. In the downy hairs, the roots pass only into the superficial layers of the true skin ; but in the thicker hairs, the roots pass through the skin and penetrate the subcutaneous cellulo-adipose tissue. The root of the hair is softer, rounder, and a little larger than the'shaft. It becomes enlarged into a rounded bulb at the bottom of the follicle, and rests upon a f ungiform papilla, constricted at its base, to which it is closely attached. In describing the connection between the hairs and the skin, anatomists mention three membranes forming the walls of the hair-follicles, and two membranes that envelop the roots of the hair in the form of a sheath. The study of these parts is much simplified by keeping constantly in view the correspondence between the different layers of the follicles and the layers of the true skin, and the relations of the root- sheaths with the epidermis. The follicles are tubular inversions of the structures that compose the coriurn, and their walls present three distinct membranes. Their length is from -^ to J of an inch. The membrane that forms their external coat is composed of 124: EXCRETION. inelastic fibres arranged for the most part longitudinally, provided with blood-vessels and a few nerves, containing some fibro-plastic elements, but deprived entirely of elastic tissue. This is the thickest of the three membranes and is closely connected with the corium. Next to this is a fibrous membrane composed of fusiform, nucleated fibres arranged transversely. These resemble the organic muscular fibres, but are believed by Kolliker to be fibres of connective tis- sue.1 The internal membrane is structureless, and corre- sponds to the amorphous layer of the true skin. The papilla at the bottom of the hair-sac varies in size with the size of the hairs, and is connected with the fibrous layers of the walls of the follicle. It is composed of amorphous matter with a few granules and nuclei, and probably contains blood- vessels and nerves, though these are not very distinct. Although these different membranes are sufficiently recog- nizable, it is evident that the hair-sac is nothing more than an inversion of the corium, with some slight modifications in the character and arrangement of its anatomical elements. The fibrous membranes correspond to the deeper layers of the true skin, wranting the elastic elements, and presenting a peculiar arrangement of its inelastic fibres, the external fibres being longitudinal and the internal fibres transverse. The structureless membrane corresponds to the upper layers of the true skin, which are composed chiefly of amorphous matter. The hair-papilla corresponds to the papillae on the general surface of the corium. The investment of the root of the hair presents two dis- tinct layers. The external root-sheath is three or four times as thick as the inner membrane, and corresponds exactly with the Malpighian layer of the epidermis. This sheath is con- tinuous with the bulb of the hair. The internal root-sheath is a transparent membrane, composed of flattened cells, mostly without nuclei. This extends from the bottom of the hair-follicle, and covers the lower two-thirds of the root. 1 KOLLIKER, Handbuch der Gewe belehre des Menscken, Leipzig, 1867, S. 132. XAIL3 AXD HAIR. 125 FIG. 5. Summary. — The essential points in the anatomy of the hair-follicles and the connections of the hairs with the skin may be summed up in a few words : The hair-follicle consists of an inversion of the true skin, with some modifications in the arrange- ment of its anatomical elements, and presents at the bottom an ovate papilla, upon which the bulb of the hair rests and to which it is closely attached. The root of the hair is invested with two mem- branes; the outer sheath corre- sponding to the Malpighian layer 'of the epidermis, and the inner sheath corresponding to the horny layer. These membranes, with the membranes that form the wall of the follicle, extend to the junction of the lower two-thirds with the upper third of the follicle, or the openings of the sebaceous glands, with which all the hairs are pro- vided. If continued upon the skin, of course the layers would be re- versed, the inner root-sheath be- o-ni epi- rrvmincr flip nntpr lavpr nf flip *vm Hair and hair-follicle of medium PIZP. ing IJ - lajei me epi- nia?nified flfty diameters-a, shaft flpvinii; flip nnfpr rr»nt dlipntTi T^oir>ry of thehair; 6, root; c. bulb, rf. epi- "Sj" >Ot-sneatn Deing dermis of the hair; V. internal root- pnntinnrmj; \vitli tViP "\ralr»irrliiQn sheath;/, external sheath; , Convo- luted tubes ; puric acid — Thudichum — equiv. to 1*00 " 1*40 Hippurate of lime. . . . ) about 8'7 grs. of hippurate of soda.) Lactate of soda \ Lactate of potassa ...!• (Daily quantity not estimated). . 1-50 " 2'60 Lactate of lime ) Creatine ) (In 24 hours, about 11 -5 grains Creatinine f of both— Thudichum) 1-60 " 3'00 Oxalate of lime (daily quantity not estimated) traces " I'lO Xanthine not estimated. Margarine, oleine, and other fatty matters O'lO to 0'20 Chloride of sodium (hi 24 hours, about 154 grains — Robin) 3'00 " 8'00 Chloride of potassium traces. Hydrochlorate of ammonia 1'50 to 2'20 Sulphate of soda. . . 1 ^ 24hr3'' 23 to 38 «"• of sulPhu- Sulphate of potassa ric acid-Thudichum. About equal Sul hate of lim f parts of sulPnate of soda and sulphate 3'00 " 7*00 of potassa — Robin — equiv. to from ' J 22-5 to 37-5 grs. of each.) Phosphate of soda, neutral l (Daily quantity not esti- Phosphate of soda, acid. . j" mated) 2'50 " 4'30 Phosphate of magnesia (in 24 hrs., 7'7 to 11 '8 grs. — Neubauer) 0'50 " 1-00 Phosphate of lime, acid. . ) (In 24 hrs., 4'7 to 5'7 grs. — Phosphate of lime, basic. . ) Neubauer) 0'20 " 1'30 Ammonio-magnesian phosphate (daily quantity not estim.). . 1'50 " 2'40 (Daily excretion of phosphoric acid, about 56 grs. — Thudichum.) Silicic acid 0'03 " 0'04 Urrosacine ^ 0.10 « Q.$Q Mucus from the bladder \ * 1,000-00 1,000-00 Gases of the Urine. (Parts per 1,000 in volume.) Oxygen, in solution ................................... 0'82 Nitrogen, in solution. (Mean of fifteen observations — Morin) 9'59 Carbonic acid, in solution ............................. 19'62 Proportion of solid constituents, from 32'63 to 59'89 parts per 1,000. 13 194 EXCRETION. Urea, C3H4N3O2. As regards quantity, and probably as a measure of the activity of the general process of disassimilation, urea is the most important of the urinary constituents ; and this sub- stance, with the changes which it undergoes in the urine and the mode of its production in the system, has been most carefully studied by physiologists. Regarding the daily ex- cretion of urea as a measure of nutritive force and physio- logical waste, its consideration would come properly under the head of nutrition, in connection with all other substances known to be the results of disassimilation ; but it is more convenientN to treat of its general physiological properties, and some of its variations in common with other excremen- titious principles separated by the kidneys, in connection with the composition of the urine. The formula for urea, showing the presence of a large proportion of nitrogen, would lead us to suppose that it is one of the products of the waste of the nitrogen ized princi- ples of the body. It is found, under normal conditions, in the urine, the lymph and chyle, the blood, the sweat, and the vitreous humor.1 Its presence has lately been demon- strated also in the substance of the healthy liver in both carnivorous and herbivorous animals;2 and it has further been shown by Zalesky that it exists in minute quantity in the muscular juice.8 Under pathological conditions, as has been already intimated, urea finds its way into various 1 MILLON, Presence de Puree dans Phumeur vitree de Fail. — Annuaire de chimie, Paris, 1848, p. 431. The discovery of urea in the vitreous humor was con- firmed by Marchand and by Wohler (Ibid., 1849, p. 540). 8 The presence of urea in the substance of the liver in diseased conditions has frequently been observed, and lately its existence has been conclusively demonstrated in the healthy liver by Meissner. (Eeitrdge zur Kenntniss des Stoffwechsels im thierischen Organismus. — Centralblatt fur die mediciniscJien Wis- scnschaften, 1868, No. 18, S. 275.) 3 ZALESKY, Untersuchungen iiber den Uraemischen Process, Tubingen, 1865, Tabelle iii. UREA. 195 other fluids, such as the secretion from the stomach, the serous fluids, etc. In connection with the chemical properties of urea, it is interesting to note that it is one of the few organic proxi- mate principles that can be produced synthetically in the laboratory of the chemist.1 As early as 1828, Wohler ob- tained urea by adding sulphate of ammonia to a solution of cyan ate of potassa.3 The products of this combination are sulphate of potassa, with cyanic acid and ammonia in a form to constitute urea. The cyanate of ammonia is isomeric with urea, and the change is effected by a simple rearrangement of its elements, the formula being NH^OjC^O (cyanate of ammonia), equivalent to C3H4]N'aO3 (urea). It has long been known that urea, in contact with certain animal substances, is readily convertible into carbonate of ammonia. This trans- formation is theoretically accomplished by adding to urea four atoms of water. C3H4N 3O, (urea) + 4 HO = 2 (KH4O,CO2). It has recently been stated by Kolbe, that when carbonate of ammonia is heated in sealed tubes to the temperature at which urea commences to decompose, it is converted into urea.3 The decomposition of urea resulting in the carbonate of ammonia may be easily effected by various chemical means. As this occurs in the spontaneous decomposition of urea in the urine and elsewhere, it has been supposed that the symptoms of blood-poisoning following retention of the urinary constit- uents, in cases of disease of the kidneys, are due to the decomposition of the urea into carbonate of ammonia, and not to the presence of the urea itself in the blood. Many interesting experiments and observations have been made upon this subject, but it is now pretty generally admitted 1 It is interesting, also, in this connection to refer to the synthesis of another of the organic proximate principles ; viz., neurine, which has lately been accom- plished by Wurtz (Comptes rendus, Paris, 1868, tome Ixv., p. 1015). 2 WOHLER, Sur la formation artificielle de Vuree. — Annales de chlmie et de physique, Paris, 1828, tome xxxvii., p. 330. 3 Journal of Anatomy and Physiology, Cambridge and London, 1868, vol. ii., p. 430. 196 EXCRETION. that the weight of evidence is against the carbonate-of- ammonia theory of uraemia. Except as regards the probable changes that take place in the process of transformation of certain constituents of the tissues into urea, the chemical history of this substance does not present much physiological interest. Urea may be read- ily extracted from the urine, by processes fully described in all the modern works upon physiological chemistry ; and its proportion may now be easily estimated by the new meth- ods of volumetric analysis. It is not so easy, however, to separate it from the blood or the substance of any of the tissues, on account of the difficulty in getting rid of the other organic matters and the great facility with which it under- goes decomposition. When perfectly pure, urea crystallizes in the form of long, four-sided, colorless, and transparent prisms, which are with- out odor, neutral, and in taste something like saltpetre. These crystals are very soluble in water and in alcohol, but are entirely insoluble in ether. In its behavior to reagents, urea acts as a base, combining readily with certain acids, particularly the nitric and oxalic. It also forms combina- tions with certain salts, such as the oxide of mercury, chlo- ride of sodium, etc. It exists in the economy in a state of watery solution, with perhaps a small portion of it modified by the presence of chloride of sodium. Origin of Urea. — There are two probable sources of urea in the economy, assuming that it always preexists in the blood and is not formed in the kidneys. One of these is in the disassimilation of the nitrogenized constituents of the tissues, and the other in a transformation in the blood of an excess of the nitrogenized elements of food. Urea, as we have already seen, exists in considerable quantity in the lymph and chyle, and is found, also, in small proportion, in the blood. It has lately been detected in still smaller quan- tity in the muscular tissue ; 1 but chemists have thus far been 1 ZALESKY, loc. dt. Meissner found urea in the muscles, liver, and brain, UREA. 197 unable to extract it from any other of the solid tissues, under normal conditions, except the substance of the liver. The fact that it exists in considerable quantity in the liver has led to the supposition that this is the organ chiefly concerned in its production.1 "With the small amount of positive information that we have upon this point, the view that the liver produces urea, while the kidneys are the organs chiefly concerned in its elimination, must be regarded as purely hypothetical. But if it be true that urea is the re- sult of the physiological wear of the nitrogenized elements of the body, the liver would probably produce its share, in the ordinary process of disassimilation. The fact that urea has not yet been detected in normal muscular tissue is by no means a conclusive argument against its formation in this situation. We have lately shown that, although the liver is constantly producing sugar, none can be detected in its substance, for the reason that it is washed out as fast as it is formed, by the current of blood.2 In the case of the muscles, it is by no means improbable that the lymph, and perhaps the blood, washes out the urea constantly, and keeps in rabbits and dogs, after extirpation of the kidneys (Bericht uber Versuche der Uramie betreffend. — Zeitschrift fur rationelk Medicin, Leipzig u. Heidelberg, 1866, Dritte Reihe, Bd. xxvi., S. 232). 1 MEISSXER, Beitrdge zur Kenntniss des Stoffwecfisels im thierischen Organis- mus. — CentralUatt fur die medidnischen Wissenschaften, 1868, Xo. 18, S. 275. Meissner refers to Heynsius and Stokvis as having previously indicated, though in an imperfect manner, the presence of urea in the liver. Parkes states that •when portions of the substance of the liver have been destroyed by disease, the urea is sometimes deficient in the urine, and that it has appeared to him that " the want of urea was hi proportion to the amount of hepatic tissue destroyed " (The Composition of the Urine, London, 1860, p. 284). 2 FLINT, Jr., Experiments undertaken for the purpose of reconciling some of the Discordant Observations upon the Glycogenic Function of the Liver. — New York Medical Journal, Jan., 1869, vol. viii., p. 373, et seq. The experiments detailed hi this article we have since repeated in public demonstrations, and confirmed most fully. In our later observations, we showed absence of sugar in the blood from the portal vein and the substance of the liver, and the presence of a large quantity of sugar in the blood from the hepatic veins. The dog upon which these observations were made was in full digestion. 198 EXCEETION. these parts free from its presence during normal conditions. In some late experiments by Meissner, in which the observa- tions of Prevost and Dumas on the accumulation of urea in the blood of nephrotomized animals were confirmed, urea was found in dogs and rabbits, after removal of the kidneys, not only in the liver, but in the muscles and brain.1 Although our experimental knowledge does not warrant the unreserved conclusion that urea is produced primarily in the nitrogenized parts of the organism, particularly the muscular tissue, this view is exceedingly probable ; and we must wait for further information on this subject, until phys- iological chemists are able to follow out more closely the exact atomic changes that intervene between the functional operation of organized parts and the change of their sub- stance into excrementitious matters. When we come to consider the influence of food upon the composition of the urine, it will be seen that an excess of nitrogenized matter taken into the alimentary canal causes a proportionate increase in the quantity of urea discharged. This fact has led to the supposition that a part of the urea contained in the urine is the result of a direct transformation in the blood of the nitrogenized alimentary principles. This view must be regarded as purely hypothetical. "We do not even know the nature of the process by which the nitroge- nized elements of the tissues are transformed into excremen- titious matter, and we are still more ignorant of the essential characters of nutrition proper. When more nitrogenized food is taken than is absolutely necessary, it is evident that the excess must be discharged from the system. This is never discharged in the same form in which it enters, like an excess of chloride of sodium or other inorganic matter, but it is well known that a series of complicated changes, called catalytic, are necessary, even before organic matters can be taken into the blood by absorption. There is 110 evi- 1 MEISSNER, Bericht uber Versuche der Urdmie betreffend. — Zeitschrift fur rationelle Medicin, Leipzig u. Heidelberg, 1866, Dritte Reihe, Bd. xxvi., S. 232. UKEA. 199 dence of the direct transformation of these principles into urea before they have become part of the organized struc- tures, except in a comparison of the proportions of nitrogen ingested and discharged ; and this proves nothing with re- gard to the nature of the intermediate processes. At the present time, the most rational supposition is, that the nitro- genized elements of food nourish the corresponding constitu- ents of the body, which are constantly undergoing conversion into excrementitious matters. Observations which have ap- peared to demonstrate the formation of urea directly from albuminoid substances have not been confirmed.1 There are certain arguments, based upon comparisons of the atomic constitution of urea with the elements of uric acid, creatine, and creatinine, in favor of the view that urea is the product of a higher degree of oxidation of the other ex- crementitious matters above-mentioned. It has been found, also, that urea may be formed artificially from uric acid, creatine, creatinine, xanthine, hypoxanthine, and some other bodies of similar nature.8 That certain bodies are mutually convertible by the addition or subtraction of a few elements of water, there can be no doubt. Examples of these simple transformations are, the change of starch (C12H10O10), dex- trine, etc., into glucose (C13H14O14) ; the change of creatine (C8H9X3O4) into creatinine (C8H7^"3O3), etc. ; but the atomic changes necessary for the conversion into urea of the princi- ples from which this substance has been assumed to be pro- duced are much more complicated. There is no positive proof that the proportion of these various principles in the muscles, blood, and urine, bears an inverse ratio to the pro- portion of urea. Again, the argument that the excrements of reptiles contain an excess of uric acid because the activity of oxidation is less than in the mammalia is met by the fact that in birds, where the amount of oxygen consumed is 1 MILNE-EDWARDS, Lemons sur la physiologic, Paris, 1862, tome vii., pp. 400, 401. 8 XEUBAUER AND VOGEL, op. tit., p. 9 200 EXCRETION. greater, the proportion of urates is enormous ; and urea is not generally found in this class, but is contained only in the excrements of the rapacious birds, and here only in small quantity.1 There are no sufficient reasons for regarding urea as the final result of oxidation of certain of the tissues of the body, uric acid, creatine, etc., being substances in an intermediate stage of transformation ; and we are forced to admit that this principle is formed during the general process of disas- similation, probably from the nitrogenized elements of the body, by a destructive action, with the exact nature of which we are as yet imperfectly acquainted. The daily amount of urea excreted is subject to very great variations. It is given in the table as ranging between 355 and 463 grains. This is much less than the estimates frequently given; but when the quantity has been very large, it has generally depended upon an unusual amount of exercise, of nitrogenized food, or the weight of the body has been above the average. Parkes gives the results of twenty-five different series of observations on this point. The lowest estimate is 286'1 grains, and the highest 688'4 grains.2 Compounds of Uric Add. Uric acid (C6ILN~2O3 + HO) seldom, if ever, exists in a free state in the normal urine. It is exceedingly insoluble, requir- ing from fourteen to fifteen thousand times its volume of cold water, and from eighteen to nineteen hundred parts of boil- ing water for its solution.3 It was at one time supposed to exist in the urine in sufficient quantity to give it its acid re- action ; but it has since been ascertained that its solution does not redden litmus. Its presence in the urine uncombined must be regarded as a pathological condition ; still, it is often 1 MILNE-EDWARDS, Lemons sur la physiologic, Paris, 1862, tome vii., p. 445. 2 PARKES, 27ic Composition of the Urine, London, 1860, p. 7. 3 NEUBAUER AND VOGEL, op. cit., p. 27. COMPOHtO)S OF URIC ACID. 201 found in urinary deposits, where it is interesting to study the peculiar and varied forms of its crystals. Frequently, in ta- bles of the composition of the urine, the proportion of uric acid is given, but this is simply a matter of convenience, and has precisely the same signification as the estimates of the proportions of sulphuric or phosphoric acid. None of these acids constitute, of themselves, proximate principles of the urine, but are always combined with bases. In normal urine, uric acid is combined with soda, ammo- nia, potassa, lime, and magnesia. Of these combinations, the urate of soda and the urate of ammonia are by far the most important and constitute the great proportion of the urates, the urates of potassa, lime, and magnesia existing only in minute traces. The urate of soda is very much more abundant than the urate of ammonia.1 The union of uric acid with the bases is very feeble. If from any cause the urine become excessively acid after its emission, a deposit of uric acid is liable to occur. The addition of a very small quantity of almost any acid is sufficient to decompose the urates, when the uric acid appears after a few hours in a crystalline form. Uric acid, probably in combination with bases, was found in the substance of the liver in large quantity by Cloetta ; a and his observations have been confirmed by recent German authorities.8 It is more than probable that the urates also exist in the blood and pass ready-formed into the urine; but their proportion in the blood is so slight under normal conditions, that their presence in this fluid has not been defi- 1 The urates of soda exist in two forms ; the neutral urate, in which there is one equivalent of the acid, and the acid urate, with two equivalents of acid. There are likewise neutral and acid urates of ammonia. The neutral salts exist hi by far the larger quantity. 2 CLOETTA, De la presence de Vinosite, de facide urique, etc., dans diverse* par- ties du corps animal. — Journal de la physiologic, Paris, 1858, tome i., p. 802. Cloetta also noted the presence of uric acid in the substance of the spleen. 3 MEISSKER, op. tit. — Centralblatt fur die meditinischen Wissenschaften, 1868, No. 15, S. 226, et seq. 202 EXCRETION. nitely determined, except in birds, where Meissner has lately found it in considerable quantity.1 The fact that the urates exist in the liver, and in no other part — except, perhaps, the spleen — has led Meissner to the opinion that this organ is the principal seat of the formation of uric acid. However this may be — and the facts do not seem sufficiently definite to lead to such an exclusive opinion — it is certainly not formed in the kidneys, but is simply separated by these organs from the blood. Meissner did not succeed in finding uric acid in the muscular tissue, though the specimens were taken from the same animals in which he had found large quantities in the liver. We have already discussed the theory of the change of uric acid into urea. In the present state of our knowledge, we must regard the urates, particularly the urate of soda, as among the products of disassimilation of the nitrogenized constituents of the body ; and we should admit that as yet we are unable to designate the precise seat of their forma- tion, or to follow out all the processes involved in their pro- duction. The daily excretion of uric acid, given in the table, is from six to nine grains ; which is equal to from nine to four- teen grains of urates estimated as neutral urate of soda. Like urea, the proportion of the urates in the urine is sub- ject to certain physiological variations, which will be con- sidered further on. IRppurates and Lactates. The compounds of hippuric acid (C18H9NO6), which are so abundant in the urine of the herbivora, are now known to be constant constituents of the human urine. Robin states that hippuric acid is always to be found in the urine of children, but that it is sometimes absent temporarily in the adult.9 The presence of this acid in the normal human 1 Loc. dt. 2 ROBIN, Lemons sur les humeurs, Paris, 1867, p. 678. HIPPUKATES AND LACTATES. 203 urine seems to have been first established by Liebig ; l and his researches have since been confirmed by numerous other observers. Lehmann, particularly, has been able to find this acid in his own urine, not only when on a purely vege- table diet, but during the use of a mixed diet. He is of the opinion that this principle frequently escapes observation when the urine has been evaporated too rapidly.3 The hippurates have been detected in the blood of the ox by Yerdeil and Dolfuss,3 and have since been found in the blood of the human subject ; 4 and there can be scarcely any doubt that they pass, ready-formed, from the blood into the urine. With regard to the exact mode of origin of the hippurates, we have even less information than upon the origin of the other urinary constituents already considered. Experiments have shown that the proportion of hippuric acid in the urine is greatest after taking vegetable food; but it is found after a purely animal diet, and probably also exists during fasting. "We must be content at present simply to class the hippurates among the products of disassimila- tion, without attempting to specify their exact mode of origin.5 The daily excretion of hippuric acid amounts to about Y'5 grains ; 6 equivalent to about 8*7 grains of hippurate of soda. Hippuric acid itself, unlike uric acid, is quite soluble in water and in a mixture of hydrochloric acid. It requires six hundred parts of cold water for its solution, and a much less proportion of warm water. Under pathological con- ditions, it is sometimes found free in solution in the urine. 1 LIEBIG, Sur facide contenu dans Furine des quadrupedes herbivores. — Annales de chimie et de physique, Paris, 1830, tome xliii., p. 188, et seq. 2 LEHMANN, Physiological Chemistry, Philadelphia, 1855, vol i., p. 179. 3 ROBIN ET VERDEIL, Chimie anatomique, Paris, 1853, tome ii., p. 446. 4 MILNE-EDWARDS, Lemons sur la physiologic, Paris, 1857, tome i., p. 201. 5 The reader is referred to works treating specially of the urine, for specu- lations concerning the origin and pathological relations of hippuric acid. An analysis of numerous observations on this subject has been made by Parkes. (Composition of the Urine, London, 1860, pp. 13, 29.) 6 THUDICHUM, A Treatise on the Pathology of the Urine, London, 1858, p. 416. 204 EXCRETION. The lactates of soda, potassa, and lime exist in very con- siderable proportion in the normal urine. They are un- doubtedly derived immediately from the blood, passing, ready-formed, into the urine, where they exist in simple wa- tery solution. According to Robin, the lactates are formed in the muscles, in the substance of which they can be read- ily detected.1 We have no positive information with regard to the precise mode of formation of these salts. It is prob- able, however, that the lactic acid is the result of transfor- mation of glucose. As a curious chemical fact, it is inter- esting to note that the lactic acid contained in the lactates extracted from the muscular substance is not absolutely identical w^ith the acid resulting from the transformation of the sugars. The former have been called paralactates, and they contain one equivalent of water less than the ordinary lactates. According to Robin, the compounds of lactic acid in the urine are in the form of paralactates.3 Although the inosates (compounds of inosine, C12H12O12) have never been detected in the urine, Robin is of the opinion that traces of these salts are separated from the blood by the ,kidneys, from the fact that they exist normally in the blood and in the muscular tissue.3 We have little or no information with regard to the re- lations of the inosates to excretion. Creatine, C8H9O4NS + 2HO, and Oreatmme, C8H7O2¥3. Creatine and creatinine are undoubtedly identical in their relations to the general process of disassimilation, for one is easily converted into the other, out of the body, by very simple chemical means ; and there is every reason to suppose that, in the organism, they are the products of physiological waste of the same tissue or tissues. These principles have been found in the urine, blood, muscular 1 ROBIN, Lemons sur les humeurs, Paris, 1867, p. 681. 2 Loc. cit. 3 Loc. cit. CREATINE A3TD CBEATININE. 205 tissue, and brain.1 Scherer has demonstrated the presence of creatine in the amniotic fluid.8 By certain chemical manipulations, both creatine and creatinine may be changed into urea ; and the fact that these substances are now known to be constant constituents of the urine leaves no doubt that they are to be classed among the excrementitious prin- ciples. Chevreul, who first discovered creatine in the ex- tract of muscular tissue, regarded it as one of the nutri- tive principles of meat ; * but the subsequent researches of Heintz,4 Liebig,5 and others, who found it in the urine, re- vealed its true character. Verdeil and Marcet e have since found both creatine and creatinine in the blood ; and these principles are now generally regarded as excrementitious matters, taken from the tissues by the blood, to be eliminated by the kidneys. Creatine has a bitter taste, is quite soluble in cold water (one part in seventy-five), and is much more soluble in hot water, from which it separates in a crystalline form on cool- ing. It is but slightly soluble in alcohol, and is insoluble in ether. A watery solution of creatine is neutral. It does not readily form combinations as a base ; but it has lately been made to form crystalline compounds with some of the strong mineral acids, the nitric, hydrochloric and sulphu- ric.7 According to Neubauer and Yogel, when boiled for a long time with baryta, it is changed into urea and sar- 1 You, Ueber das Verhdten des Kreatins, Kreatinins und Harnstoffs im Thier- korper.— Zeitechrift fur Biologie, Miinchen, 1868, Bd.iv., S. 78. 2 SCHERER, Analyse d'un liquide amniotique. — Annuaire de chimie, Paris, 1850, p. 576. 3 CHEVREUL, Uhtersuchungen uber die chemische Zusammensdzung der Fleisch- briihe. — Journal fur praktische Chemie, Leipzig, 1835, Bd. vi., S. 120, et seq. 4 HEINTZ, Ueber eine nene Sdure im menschlichen Ham. — Annalen der Physik und Chemie, Leipzig, 1844, Bd. Ixii., S. 602. 5 LIEBIG, Recherches de chimie medicate. — Comptes rendus, Paris, 1847, tome xxiv., p. 69, et seq. 6 ROBIN ET YERDEIL, Tratte de chimie anatomique, Paris, 1853, tome ii., pp. 480, 489. 7 XEUBAUER AND VOGEL, op tit., p. 17. 206 EXCRETION. cosine ; but the recent researches of Yoit have pretty con- clusively shown that this change does not take place in the living organism, and that probably none of the urea of the urine is produced in this way.1 "When boiled with the strong acids, creatine(C8H9O4N3 + 2HO) loses four atoms of water, and is changed into creatinine (C8H7O2N3). This change takes place very readily in decomposing urine ; which con- tains neither urea nor creatine, but a large quantity of crea- tinine, when far advanced in putrefaction. Creatinine is more soluble than creatine, and its watery solution has a strong alkaline reaction. It is dissolved by eleven parts of cold water, and is even more soluble in boiling water. It is slightly soluble in ether, and is dis- solved by one hundred parts of alcohol. This substance is regarded as one of the most powerful of the organic bases, readily forming crystalline combinations with a number of acids. According to Thudichum, who has very closely stud- ied the physiological relations of these substances, creatine is the original excrement itious principle produced in the muscular substance, and creatinine is formed in the blood by a transformation of a portion of the creatine, somewhere between the muscles and the kidneys ; " for, in the muscle, creatine has by far the preponderance over creatinine ; in the urine, creatinine over creatine." ' In the present state of our knowledge, there is very little to be said with regard to the physiological relations of crea- tine and creatinine, except that they are probably to be classed among the excrementitious principles resulting from the disassimilation of the muscular tissue. As they exist in considerable quantity in the muscular substance, it be- comes a question whether, in the urine of carnivorous ani- mals, they are not derived from the food ; but they could have no such origin in the herbivora, nor in the urine of 1 VOIT, Ueber das Verlialten des Kreatins, Kreatinins und Harnstoffs im Thier- korper. — Loc. cit., p. 116. 2 THUDICHUM, Pathology of the Urine, London, 1858, p. 120. CKEATINE AUD CREATINIXE. 207 starving animals. Thudichum mentions the fact that they are particularly abundant in the muscles of wild animals, and that the proportion diminishes in the same animals dur- ing captivity. He cites the instance of a fox that had been fed on meat for two hundred days at the Anatomical Insti- tution in Giessen, in which the proportion of creatine was not one-tenth part that contained in the flesh of foxes caught by hunting.1 It has likewise been found that the propor- tion of creatine is very small in fat meat. It has been assumed by many authors that inasmuch as the muscular tissue of the heart is in almost constant action, it should contain more creatine than any other portion of the muscular system;2 but the late observations on this point by Hofrnann, Halenke, and Yoit, show that the re- verse of this is the case. These physiologists compared the proportion of creatine in the heart and in the muscles of the extremities, in oxen and in the human subject, and al- ways found the quantity much less in the heart ; 3 still the proportion of creatine has been found to be greater in tetan- ized muscles than in the muscular tissue after repose. From the meagreness of our facts with regard to the phys- iological relations of creatine and creatinine, it is evident that there is much to be learned before we can understand the process of its formation in the healthy organism and the probable results of its retention or deficient elimination in disease. At present we can only say that these principles are probably produced in greatest part in the muscular tis- sue. The fact that creatine has lately been demonstrated in the brain would lead to the supposition that it is also one of the products of disassimilation of the nervous substance. The average daily excretion of creatine and creatinine is estimated by Thudichum at about 11-5 grains. Of this he 1 Op. tit., p. 120. 2 THUDICHUM, loc. cit. ROBIX ET YERDEIL, Traite de chimie anatomique, Paris, 1853, tome ii., p. 481. 3 YOIT, loc. tit., p. 84. 208 EXCRETION. estimates that 4*5 grains consist of creatine, and 7 grains, of creatinine.1 Oxalate of Lime, CaO,C3O3 + 2HO. This salt is not constantly present in the normal human urine, though it may exist in considerable quantity without denoting any pathological condition. It is exceedingly inso- luble, and the appearance of its crystals in urinary deposits is very characteristic. According to Robin, a trace may be re-A tained in solution by the chlorides and the alkaline phosphates in the urine.3 This salt may find its way out of the system by the kidneys, after it has been taken with vegetable food or with certain medicinal substances. The ordinary rhubarb, or pie-plant, contains a large quantity of oxalate of lime, which, when this article is taken, will pass into the urine. It is probable, however, that a certain quantity of the oxa- late may be formed in the organism. Pathologists now recognize a condition called oxaluria, characterized by the appearance of oxalate-of-lime crystals in the urinary sedi- ments ; and sometimes the quantity in the urine is so large, and its presence is so constant, that it forms vesical calculi of considerable size. Inasmuch as pathological facts have shown pretty con- clusively that oxalic acid may appear in the system without being introduced with the food, some physiologists have en- deavored to show how it may originate from a change in cer- tain other of the proximate principles from which it can be produced artificially out of the body. One of the substances from which oxalic acid can be thus formed is uric acid. It remains, however, to show that this may take place in the living organism. Woehler and Frerichs injected into the jugular vein of a dog a solution containing about twenty- three grains of urate of ammonia. In the urine, taken a 1 THUDICHUM, A Treatise on the Pathology of the Urine, London, 1858, p. 416. 2 ROBIN, Lemons sur les humeurs, Paris, 1867, p. 674. XANTHIXE. 209 short time after, there was no deposit of uric acid, but there appeared numerous crystals of oxalate of lime. The same result followed in the human subject, on the administration of sixty-seven grains of urate of ammonia by the mouth.1 These questions have more of a pathological than a physio- logical interest ; for the quantity of oxalate of lime in the normal urine is insignificant, and this salt does not repre- sent any of the well-known processes of disassimilation; Xanthine (C10H6!N"4O4). — Traces of this substance have been found in the normal human urine, but its proportion has not been estimated, and we are as yet but imperfectly acquainted with its physiological relations. Under pathologi- cal conditions, it occasionally exists in sufficient quantity to form urinary calculi. It has been found in the liver, spleen, thymus, pancreas, muscles, and brain. It is insoluble in wa- ter, but is soluble in both acid and alkaline fluids. Hypo- xanthine (C10H4N"4O2) has never been found in normal urine, though it exists in the muscles, liver, spleen, and thymus. Leucine (C12H,aN"aO4) exists in the pancreas, salivary glands, thyroid, thymus, suprarenal capsules, lymphatic glands, liver, lungs, kidney, and gray substance of the brain. It has never been detected in the normal urine. The same remarks apply to tyrosine (C18HnNO6), though it is not go extensively distributed in the economy, taurine (C4H7]N~O6S3), and cys- tine (C6H6N4O4S2). The last two, however, contain sulphur, and may have peculiar physiological and pathological rela- tions that we do not at present understand. These various substances are mentioned, though some of them have not been demonstrated in the normal urine, for the reason that there is evidently much to be learned with regard to the various products of disassimilation as they are represented by the composition of the urine. While some 1 WOEHLER TTND FRERiCHS, Ueber die Verdnderungen, welche namentUch or- ganische Stoffe lei ihren Uebergange in den Horn erleiden. — Journal fur tische Chimie, Leipzig, 1848, Bd. xliv.,S. 65. 14 210 EXCRETION. of these may not be actual proximate principles, but sub- stances produced by the processes employed for their extrac- tion, some, which have thus far been discovered only under pathological conditions, may yet be found in health, and they represent, perhaps, important physiological acts.1 Fatty Matter. — A certain quantity of fat and fatty acids are said to exist in the normal urine.2 Their proportion, however, is small, and the mere fact of their presence, only, is of physiological interest. Inorganic Constituents of the Urine. It is by the kidneys that the greatest quantity and variety of inorganic principles are discharged from the organism; and it is probable that even now we are not acquainted with the exact proportion and condition of all the principles of this class contained in the urine. In all the processes of nu- trition, it is found that the inorganic constituents of the blood and tissues accompany the organic matters in their various transformations, though they are themselves unchanged. In fact, the condition of union of the inorganic with the or- ganic principles is so intimate, that they cannot be com- pletely separated without incineration. In view of these facts, it is evident that a certain part, at least, of the inor- ganic salts of the urine is derived from the tissues, of which, in combination with organic matters, they have formed a constituent part. As the kidneys frequently eliminate from the blood foreign matters taken into the system, and are capable sometimes of throwing off an excess of the normal constituents which may be introduced into the circulation, it can be readily understood how a large proportion of some 1 For further information concerning these principles, the reader is referred to works treating of the pathology as well as the physiology of the urine. A succinct statement of our positive knowledge regarding the doubtful principles is given by Robin (Leyons sur les humeurs, Paris, 1867, p. 688, et seq.). 2 ROBIN, op. cit.t p. 690. INORGANIC CONSTITUENTS OF THE TJKINE. 211 of the inorganic matters of the urine is derived from the food. From the fact that the inorganic matters discharged in the urine are generally the same as those introduced with the food, and that they vary in proportion with the consti- tution of the food, it is difficult to ascertain how far their presence and quantity in the urine represent the processes of disassimilation. One thing, however, is certain : that the organic constituents of the food, the blood, the tissues, and the urine, are never without inorganic matter in considera- ble variety ; and it is more than probable that the presence of these salts in a tolerably definite proportion influences the processes of absorption and secretion and has an important bearing upon nutrition ; but we are as yet so imperfectly acquainted with the processes of nutrition of the tissues, that we cannot follow out all the relations of the inorganic mat- ters, first to nutrition, and afterward to disassimilation. Chlorides. — Almost all of the chlorine in the urine is in the form of chloride of sodium ; the amount of chloride of potassium being insignificant and not of any special physio- logical importance. It is unnecessary, in this connection, to describe the well-known properties of common salt ; and the means for determining its presence and proportion in the urine are fully treated of in works upon physiological chem- istry. All that we have to consider is its importance and sig- nificance as a urinary constituent. By reference to the table of the composition of the urine, it is seen that the proportion of chloride of sodium is subject to very great variations, the range being from three to eight parts per thousand. This at once suggests the idea that the quantity excreted is dependent to a considerable extent upon the amount taken in with the food ; and, indeed, it has been shown by numerous observations that this is the fact.1 The 1 THUDICHUM, A Treatise on the Pathology of the Urine, London, 1858, p. 162. — XEUBAUER AND YOGEL, A Guide to the Qualitative and Quantitative Analysis of 212 EXCRETION. proportion of chloride of sodium in the blood seems to be tolerably constant ; and any excess that may be introduced is thrown off chiefly by the kidneys. It has been shown con- clusively that deprivation of common salt in the food after a time is followed by serious disturbances in the general pro- cess of nutrition ; and it is an acknowledged fact that this proximate principle is a constituent of every tissue of the body, except the enamel of the teeth. As the chlorides are deposited with the organic matter in all the acts of nutrition, they are found to be eliminated constantly with the products of disassimilation of the nitrogenized parts, and their absence from the food does not completely arrest their discharge in the urine. According to Robin, by suppressing salt in the food, its daily excretion may be reduced to from thirty to forty-five grains, the normal quantity being from one hundred and fifty to one hundred and sixty grains. This quantity is less than the amount contained in the ingesta, and under these circumstances there is a gradual diminution in the nutritive activity. " This fact demonstrates the necessity of adding chloride of sodium to the food." J It is an interesting patho- logical fact, that in all acute febrile disorders, the proportion of chlorine in the urine rapidly diminishes, and is frequently reduced to one hundredth of the normal amount.3 The quantity rapidly increases to the normal standard during convalescence. Most of the chlorides of the urine are in simple watery solution; but a certain proportion of the chloride of sodium exists in combination with urea. The daily elimination of chloride of sodium is about one hundred and fifty-four grains (Robin). The great variations in its proportion in the urine under different conditions of alimentation, etc., will explain the differences in the esti- mates given by various authorities. the Urine, New Sydenham Society, London, 1863, p. 396. — ROBIN, Lemons sur Ifs humeurs, Paris, 1867, p. 662. 1 ROBIN, op. cit., p. 663. 2 NEUBAUER AND VOGEL, op. cit., p. 397. INORGANIC CONSTITUENTS OF THE TJKINE. 213 Sulphates. — There is very little to be said regarding the sulphates, beyond the general statements concerning the in- organic principles of the urine. The proportion of these salts is here very much greater than in the blood, in which there exists only about 0*28 of a part per thousand. Inas- much as the proportion in the urine is from three to seven parts per thousand, it seems probable that the kidneys elimi- nate these principles as fast as they find their way into the circulating fluid either from the food or from the tissues.1 Like other principles derived in great part from the food, the normal variations in the proportion of sulphates in the urine are very great. It is unnecessary to consider in detail the variations in the amount of sulphates discharged in the urine, depending upon the ingestion of different salts or upon diet, for all the recorded observations have been followed by the same results, and show that the ingestion of sulphates in quantity is followed by a corresponding increase in the proportion eliminated. Numerous experiments on this point have been made by Yogel and others.1 Thudichum estimates the daily excretion of sulphuric acid at. from twenty-three to thirty-eight grains.3 Assum- ing, with Eobin, that the sulphates consist of about equal parts of sulphate of potassa and sulphate of soda, with traces of sulphate of lime,4 the quantity of salts would be from 22*5 to 37*5 grains of sulphate of potassa and an equal quantity of sulphate of soda. Phosphates. — The urine contains phosphates in a variety of forms ; but inasmuch as it is not known that any one of the different combinations possesses peculiar relations to the process of disassirnilation, as distinguished from the other phosphates, the phosphatic salts may be considered together. 1 ROBIN, Lemons sur les humeurs, Paris, 1867, p. 663. 2 XEUBAUER AXD VOGEL, op. cit, p. 404. 3 THUDICHUM, A Treatise on the Pathology of the Urine, London, 1858, p. 416. 4 ROBIN, loc. cit. 214 EXCKETTON. The remarks which we have just made with regard to the chlorides and the sulphates are applicable, to a certain ex- tent, to the phosphates. These salts exist constantly in the urine, and are derived in part from the food, and in part from the tissues. Like other inorganic matters, they are united with the nitrogenized elements of the organism, and when these are changed into excrementitious principles, and are separated from the blood by the kidneys, they pass with them and are discharged from the organism. It becomes a question of importance, now, to consider how far the phosphates are derived from the tissues, and what proportion comes directly from the food. This point is peculiarly interesting, from the fact that phosphorus has been shown to exist in the nerve-tissue, and it has been in- ferred that the excretion of phosphates represents, to some extent, the physiological wear of the nervous system. All observers agree that the quantity of phosphates in the urine is in direct relation to the proportion in the food, and that an excess of phosphates taken into the stomach is immediately thrown off by the kidneys.1 It is a familiar fact, indeed, that the phosphates are deficient and the car- bonates predominate in the urine of the herbivora, while the reverse obtains in the carnivora ; and that variations, in this respect, in the urine may be produced by feeding animals with different kinds of food. Yerdeil made some very inter- esting comparative analyses of the blood for the alkaline phosphates in the herbivora, the carnivora, and in man*. He found the proportion very small in the ox, as compared with the dog, and intermediate in the human subject. The pro- portion of phosphates in the blood of the dog was greatly diminished by feeding with potato.2 Deprivation of food di- minishes the quantity of phosphates in the urine, but a certain 1 NEUBAUER AND VOGEL, op. tit., p. 411. HAMMOND, On the Excretion of Phosphoric Add by the Kidneys. — Physio- logical Memoirs, Philadelphia, 1863, p. 29, et seq. 2 ROBIN ET VERDEIL, Chimie anatomique, Paris, 1853, tome ii., p. 330. INORGANIC CONSTITUENTS OF THE URINE. 215 proportion is discharged, derived exclusively from the tissues. We have already noted the fact that the products of disassim- ilation of the nitrogenized principles are never discharged in health without being accompanied with certain inorganic salts, such as the chlorides, sulphates, and phosphates. In connection with the fact that phosphorus exists (in precisely what condition it is not known) in the nervous matter, it has been stated that mental exertion is always at- tended with an increase in the elimination of phosphates ; and this has been advanced to show that these salts are specially derived from disassimilation of the brain-substance. Experiments show that it is not alone the phosphates that are increased in quantity under these conditions, but urea, the chlorides, sulphates, and inorganic matters generally;1 and in point of fact, any physiological conditions which increase the proportion of nitrogenized excrementitious principles in- crease as well the elimination of inorganic matters. It can- not be assumed, therefore, that the discharge of phosphates is specially connected with the activity of the brain. We learn nothing from pathology upon this point, for although numer- ous observations have been made upon the excretion of phosphoric acid in disease — Vogel having made about one thousand different analyses in various affections* — no defi- nite results have been obtained. From these facts it is seen that there is no physiological reason why we are able to connect the elimination of the phosphates with the disassimilation of any particular tissue or organ, especially as these salts in some form are univer- sally distributed in the organism. 1 HAMMOND, Urological Contributions. — American Journal of the Medical Sciences, Philadelphia, 1856, Xew Series, vol. xxxi., p. 334. BYASSOX, Essai sur la relation qui existe d Vetat physiologique entre Vactivite cerebrale et la composition des urines, Paris, 1868, p. 66. By reference to the table by Byasson on page 48, it will be seen that the proportion of sul- phuric acid in the urine is more than doubled by mental exertion, while the proportion of phosphoric acid is increased less than one-third. 2 NEUBAUER AND VOGEL, op. tit., p. 413, et seq. 21 6 EXCRETION. Observations have been made upon the hourly variations in the discharge of phosphoric acid at different periods of the day ; but these do not appear to bear any absolute relation to known physiological conditions, not even to the process of digestion.1 Of the different phosphatic salts of the urine, the most important are those in, which the acid is combined with soda. These exist in the form of the neutral and acid phosphates. The acid salt has one equivalent of the base, and is supposed to be the cause of the acidity of the urine at the moment of its emission. The so-called neutral salt is slightly alkaline, and has two equivalents of base. The proportion of the phosphates of soda in the urine is larger than that of any of the other phosphatic salts, but the daily amount excreted has not been estimated. The phosphate of magnesia is a constant constituent of the urine, as well as the acid and the basic phos- phate of lime. The daily excretion of phosphate of magne- sia amounts to from 7 *T to 11*8 grains, and of the phosphates of lime, from 4'Y to 5*7 grains.2 According to Robin, there always exists in the urine a small quantity of the ammonio- magnesian phosphate, but it never, in health, exists in suffi- cient quantity to form a crystalline deposit.8 The daily excretion of the phosphates is, as we have seen, subject to great variations, but the average quantity of phosphoric acid excreted daily may be estimated at about fifty grains, or, more accurately, fifty-six grains.4 The urine contains, in addition to the inorganic prin- ciples above described, a small quantity of silicic acid ; but, as far as we know, this has no physiological im- portance. 1 The reader is referred to the work of Neubauer and Vogel for a fuller consideration of the physiological and pathological relations of the phos- phates. 2 NEUBAUER AND VOGEL, op. cit., p. 59. 3 ROBIN, Lemons sur les humeurs, Paris, 1867, p. 6"66. 4 THUDICHUM, A Treatise on the Pathology of the Urine, London, 1858, p. 416. COLORING MATTER AND MUCUS. 217 Coloring Matter and Mucus. The peculiar color of the urine is due to the presence of a nitrogenized principle, known to physiological chemists under a variety of names. We have mentioned it in the table as urrosacine. It is also called urochrome, urohsema- tine, uroxanthine, and purpurine. "We have no accurate account of its ultimate composition, and all that is known about its constituents is that it contains carbon, oxygen, hydrogen, and nitrogen, and probably iron.1 Although its exact ultimate composition is not absolutely settled, its con- stituents are supposed to be the same as those of the coloring matter of the blood, the proportion of oxygen being very much greater. These facts point to the probability of the formation of urrosacine from hsematine. The quantity of coloring matter in the normal urine is very small. It is subject to considerable variation in disease, and almost always is fixed by deposits and calculi of uric acid or the urates, giving them their peculiar color. This principle first makes its appearance in the urine, and is prob- ably formed in the kidneys. So little is known of its phys- iological or pathological relations to the organism, that it does not seem necessary to follow out all of the chemical de- tails of its behavior in the presence of different reagents. The normal urine always contains a small quantity of mucus, with more or less epithelium from the urinary pas- sages, and a few leucocytes. These form a faint cloud in the lower strata of healthy urine, after a few hours' repose. The properties of the different kinds of mucus have already been considered.8 An important peculiarity, however, of the mucus contained in normal urine is that it does not seem to excite decomposition of the urea, and that the urine may remain for a long time in the bladder without undergoing any putrefactive change. 1 ROBIN ET VERDEIL, Chimie anatomique, Paris, 1853, tome iii., p. 398. 2 See page 51. 218 EXCRETION. Gases of the Urine. In the process of separation of the urine from the blood by the kidneys, a certain proportion of the gases in solution in the circulating fluid is also removed. For a long time, indeed, it has been known that the normal human urine con- tained different gases, but lately some very interesting ob- servations on this subject have been made by M. Morin,1 in which the proportions of the free gases in solution have been accurately estimated. By using the method employed by Magnus in estimating the gases of the blood,2 Morin was able to extract about two and a half volumes of gas from a hundred parts of urine. By careful experiments, he ascer- tained that a certain quantity of gas remained in the urine, and could not be extracted by his ordinary process. This amounted to about one-fifth of the whole volume of gas. Adding this to the quantity of gas extracted, he obtained the proportions to one litre of urine, in cubic centimetres, which are given in the table, viz. : Oxygen 0*824 Nitrogen 9'589 Carbonic acid 19*620 These proportions represent the average of fifteen obser- vations upon the urine secreted during the night. The proportion of these gases was found by Morin to be subject to certain variations. For example, after the inges- tion of a considerable quantity of water or any other liquid, the proportion of oxygen was considerably increased (from 0*824, to 1*024:), and the carbonic acid was diminished more 1 MORIN, Recherches sur les gas libres de Vurine. — Journal de pharmacie et de chimie, Paris, 1864, tome xlv., p. 396, et seq. 2 The method of Magnus as applied to the gases of the urine does not in- volve the elements of inaccuracy which we have pointed out with reference to the blood (see vol. i., Respiration, p. 462) ; for in the urine there is no tendency to the disappearance of oxygen and the formation of carbonic acid, such as is due in the blood to the action of the corpuscles. VARIATIONS LST THE TTBIXE. 219 than one-half. The most interesting variations, however, were in connection with muscular exercise. After walking a long distance, the exercise being taken both before and after eating, the quantity of carbonic acid was found to be double that contained in the urine after repose. The pro- portion of oxygen was very slightly diminished, and the nitrogen was somewhat increased. The variations of these gases, however, were insignificant. florin explains the great increase in the proportion of carbonic acid, by the greater respiratory activity during exercise. It is well known, indeed, that muscular exercise largely increases the proportion of carbonic acid in the blood and the quantity eliminated by the lungs ; and as the car- bonic acid of the urine is undoubtedly derived from the blood, we should expect that the same conditions would in- crease its proportion in this secretion. It is not probable that the kidneys are very important as eliminators of carbonic acid from the system, but it is cer- tain that the presence of this gas in the urine assists in the solution of some of the saline constituents of this fluid, no- tably the phosphates. Variations in the Composition of the Urine. The urine represents in its varied constituents not only a great part of the physiological disintegration of the organ- ism, but it contains elements evidently derived from the food. Its constitution is varying with every different con- dition of nutrition, with exercise, bodily and mental, with sleep, age, sex, diet, respiratory activity, the quantity of cu- taneous exhalation, and, indeed, with every condition that affects any part of the system. There is no fluid in the body that contains such a variety of principles, as a constant con- dition, but in which the proportion of these principles is so variable. It is for this reason that we have given in the table of the composition of the urine the ordinary lim- 220 ' EXCRETION. its of variation of its different constituents; and it has been found necessary, in treating of the individual excre- mentitious principles, to refer to some of the variations in their proportion in the urine. In treating more specially of the physiological variations of the urine, we shall only refer in general terms to conditions that produce wide and important changes in the proportion of its constituents ; and under the head of nutrition, we will consider how far the absolute quantities of the urinary principles and other ex- crementitious substances represent the physiological waste which is always coincident with the repair of parts. A full and complete history of all the variations in the urine would be inconsistent with the scope of this work.1 Variations with Age and Sex. — There are decided dif- ferences in the composition of the urine at different periods of life and in the sexes. These must depend in part upon the different conditions of nutrition and exercise, and in part upon differences in the food. Although the quantities of excrementitious matters present great variations, their re- lations to the organism are not materially modified, except, perhaps, at an early age ; and the influence of sex and age is merely felt as they affect the diet and general habits of life. It is stated by most authors that the urine of the foetus is highly albuminous ' and contains no urea; but examina- tions of the urine in the foetus and newly born have been so few that we know very little regarding its constitution and normal variations. The researches of the authorities on this subject, quoted by Parkes,3 leave the question of the composition of the urine in the foetus and during the first 1 For more extended details of the variations of the urine in health and dis- ease, the reader is referred to special treatises. Dr. Parkes considers these points very fully. (PARKES, The Composition of the Urine in Health and Disease, and under the Action of Remedies, London, 1859, pp. 39-179.) 5 Op. tit., p. 41, etseq. VARIATIONS IN THE HEINE. 221 days of extra-uterine life still uncertain. In a specimen of urine taken from a still-born child delivered with forceps, examined by Drs. Elliot and Isaacs, the presence of urea was determined beyond a doubt. This urine was of a pale straw-color, like clear syrup in consistence, of an acid re- action, and a specific gravity of 1007*5. It contained neither sugar nor albumen. Well-marked crystals of the nitrate and of the oxalate of urea were obtained from this specimen.1 Dr. Beale found urea in a specimen taken at the seventh month.3 With our present imperfect knowledge of the compo- sition of the urine at the earliest periods of existence, it is impossible to deduce any conclusions regarding the pro- duction of the excrementitious principles at this time ; and it would be unprofitable to detail the unsatisfactory and conflicting examinations to be found in works devoted spe- cially to the urine. Observations upon children between the ages of three and seven are more definite. At this period of life, the amount of urea excreted in proportion to the weight of the body is about double that in the adult. The amount of chlo- rine in children is about three times the quantity in the adult ; and the proportionate amount of other solid matters is also greater. The amount of water excreted by the kid- neys in children, in proportion to the weight of the body, is very much greater than in the adult, being more than double. From eight years of age to eighteen, the urinary excretion becomes gradually reduced to the adult standard.3 It has been noticed by Gallois, that crystals of oxalate of lime are much more frequent in the urine of children between four and fourteen years of age than in the adult.4 1 ELLIOT, Urine in Foetal Life. — American Journal of the Medical Sciences, Philadelphia, 1857, New Series, vol. xxxiii., p. 555. 8 BEALE, Kidney Diseases, Urinary Deposits, and Calculous Disorders, Phila- delphia, 1869, p. 125. 3 PARKES, op. cit., pp. 44, 45. * GALLOIS, De F oxalate de chaux, Paris, 1859, p. 14. 222 EXCRETION. There are not many definite observations on record upon the composition of the urine in the latter periods of life. It has been shown, however, that there is a decided diminution, at this period, in the excretion of urea, and that the absolute quantity of the urine is somewhat smaller. The absolute quantity of the urinary excretion in women is less than in men, and the same is true of the proportionate amount of these principles to the weight of the body ; still, the differences in the proportionate excretion are not very marked, and the amount of all these principles being subject to modifications from the same causes as in men, the small deficiency, in the few direct observations upon record, may be in part, if not entirely, explained by the fact that women usually perform less mental and physical work than men, and that their digestive system is generally not so active. Variations at Different Seasons, and at Different Peri- ods of the Day. — The changes in the quantity and com- position of the urine which may be directly referred to the conditions of digestion, temperature, sleep, exercise, etc., have long been recognized by physiologists ; but it is difficult, if not impossible, so to separate these influences, that the true modifying value of each can be fully appre- ciated. For example, there is nothing which produces such marked variations in the composition of the urine as the digestion of food. So marked, indeed, is its influence, that some writers of authority incline to the belief that the greatest part of what have been regarded as the most im- portant excrementitious matters is derived from the food, and not from physiological disintegration of the tissues. Under strictly physiological conditions, the modifying in- fluence of digestion must always complicate observations upon the effects of exercise, sleep, season, period of the day, etc. ; and the urine is continually varying in health, with the physiological modifications in the other processes and conditions of life. It will be sufficient for our purpose VARIATIONS IN THE URESE. 223 to note the most important of these variations and endeavor to appreciate the conditions which combine to produce them, assigning to each one its proper value. At different seasons of the year and in different climates, the urine presents certain variations in its quantity and com- position. It seems necessary that a tolerably definite quan- tity of water should be discharged from the body at all times ; and when the temperature or hygrometric condition of the atmosphere is favorable to the action of the skin, as in a warm, dry climate, the quantity of water in the urine is diminished, and its proportion of solid matters correspond- ingly increased. On the other hand, the reverse obtains when the action of the skin is diminished from any cause. This fact is a matter of common remark, as well as of scien- tific observation. At different periods of the day, the urine presents con- stant and important variations. It is evident that the spe- cific gravity must be constantly varying with the proportion of water and solid constituents. According to Dalton, the urine first discharged in the morning is dense and highly col- ored ; that passed during the forenoon is pale and of a low specific gravity ; and in the afternoon and evening it is again deeply colored, and its specific gravity is increased.1 The acidity is also subject to tolerably definite diurnal variations, which have already been noted.3 Variations produced ~by Food. — An immense number of observations have been made upon the influence of ordi- nary food, and upon diet restricted to particular articles. These facts have necessarily been considered more or less fully in connection with the origin of the urinary constit- uents ; but it is important, in studying the influence of mus- cular exercise, mental effort, etc., to constantly bear in mind the variations occurring under the influence of the ingesta* 1 D ALTON, A Treatise on Human Physiology, Philadelphia, 1867, p. 335. 2 See page 190. 224: EXCRETION. "Water and liquids generally always increase the propor- tion of water in the urine and diminish the specific gravity. This is so marked after the ingestion of large quantities of liquids, that the urine passed under these conditions is sometimes spoken of by physiologists as the urina potus. This must be borne in mind in clinical examinations of the urine. It is a curious fact, however, that when an excess of water has been taken for purposes of experiment, the diet being carefully regulated, the absolute amount of solid mat- ters excreted is considerably increased. This is particularly marked in the urea, but it is noticeable in the sulphates and phosphates, though not to any great extent in the chlorides. The results of experiments on this point seem to show that water taken in excess increases the activity of disassimi- lation.1 The ordinary meals invariably increase the solid constit- uents of the urine ; the most constant and uniform increase being in the proportion of urea. This, however, depends to a great extent upon the kind of food taken. The increase is usually noted during the first hour after a meal, and at- tains its maximum at the third or fourth hour. The inor- ganic matters are increased, as well as the excrementitious principles proper. The urine passed after food has been called urina cibi, under the idea that it is to be distinguished from the urine supposed to be derived exclusively from disas- similation of the body, the urina sanguinis. It is an interesting and important question to determine the influence of different kinds of food upon the composition of the urine, particularly the comparative effects of a nitrogen- ized and a non-nitrogenized diet. Lehmann has made some very striking observations upon this point, and his results have been fully confirmed by many other physiologists of author- ity. Without discussing elaborately all of these observations, it is sufficient to state that the ingestion of an excess of ni- trogenized principles always produced a great increase in 1 PARKES, op. cit., p. 67, et seq. IN THE UKDsE. 225 the proportion of the nitrogenized constituents of the urine, particularly the urea. On a non-nitrogenized diet, the pro- portion of urea was found to be diminished more than one- half. The results of the experiments of Lehmann are so striking that we quote them in full : " My experiments show that the amount of urea which is excreted is extremely dependent on the nature of the food which has been previously taken. On a purely animal diet, or on food very rich in nitrogen, there were often two- fifths more urea excreted than on a mixed diet ; while, on a mixed diet, there was almost one-third more than on a purely vegetable diet ; while, finally, on a non-nitrogenous diet, the amount of urea was less than half the quantity excreted during an ordinary mixed diet. " In my experiments on the influence of various kinds of food on the animal organism, and especially on the urine, I arrived at the above results, which in mean numbers may be expressed as follows : On a well-regulated mixed diet I dis- charged, in twenty-four hours, 32*5 grammes of urea (I give the mean of fifteen observations) ; on a purely animal diet, 53*2 grammes (the mean of twelve observations) ; on a vege- table diet, 22*5 grammes (the mean of twelve observations) ; and on a non-nitrogenous diet, 15 '4 grammes (the mean of three observations)." 1 With regard to the influence of food upon the inorganic constituents of the urine, it may be stated in general terms that the ingest ion of mineral substances increases their pro- portion in the excretions. "We have already alluded to this fact in treating of the different inorganic salts. There are certain articles which, when taken into the system, the diet being regular, seem to retard the process of 1 LEHMAXX, Physiological Chemistry, Philadelphia, 1855, vol. L, pp. 150, 151. These results were fully confirmed in the very interesting experiments of Prof. Hammond upon the nutritive value of albumen, starch, and gum, when singly and exclusively used as food ( Transactions of the American Medical As- sociation^ Philadelphia, 1857, vol. x., p. 513, et seq.). 15 226 EXCRETION. disassimilation ; or, at least, they diminish in a marked man- ner the amount of matters excreted, particularly the urea. Alcohol has a very decided influence of this kind. Its ac- tion may be modified by the presence of salts and other matters in the different alcoholic beverages, but in all direct experiments, alcohol, taken either under normal conditions of diet, when the diet is deficient, or when it is in excess, diminishes the excretion of urea. The same is true of tea and coffee.1 Influence of Muscular Exercise. — There can be no doubt that muscular exercise, under ordinary conditions of diet, in- creases the proportion of many of the solid constituents of the urine, particularly the urea. It is impossible to come to any other conclusion after studying the elaborate researches of Lehmann,a Hammond,3 and others upon this subject. It must be remembered, in considering the effects of exercise upon the elimination of excrementitious matters, that the modifications in the urine produced by food are very consid- erable. "We have purposely considered the influence of food before taking up other modifying conditions, so as to make apparent an important element of error in some recent ob- servations, which are at variance with the prevailing ideas on this subject. When, for example, it has been shown that restriction to a non-nitrogenous diet will immediately dimin- ish the daily elimination of urea more than one-half, it is evident that the diet must always be fully considered in ex- periments upon the effects of exercise or other modifying circumstances. There is another important point, also, which is not al- ways taken into consideration in comparative observations 1 This subject has already been considered under the head of Alimentation. See vol. ii., Alimentation, p. 102, et seq. 2 LEHMANN, Physiological Chemistry, Philadelphia, 1855; vol. i., p. 151. 8 HAMMOND, The Relations which exist between Urea and Uric Acid. — American Journal of the Medical Sciences., Philadelphia, January, 1865, and Physiological Memoirs, Philadelphia, 1863, p. 13. VARIATIONS IN THE URINE. 227 upon the absolute quantities of urea eliminated during exer- cise and repose, and that is the elimination of this principle by the cutaneous surface. We have already seen that urea is a constant constituent of the sweat. Speck, who found that exercise usually increased the elimination of excremen- titious matters, noted the fact that urea was not increased in the urine when the sweat was very abundant.1 The very elaborate analysis of the principal observa- tions on this subject by Parkes shows the discrepancies in the experiments of different authors, and points out several of the sources of error.2 The weight of experimental evi- dence at that time was decidedly in favor of an increase in the elimination of urea by exercise ; and the observations opposed to this view involved inaccuracies which would ex- plain, in part at least, the contradictory results obtained. Lately, new observations have been made, which are assumed by some to show an actual diminution by exercise in the quantity of urea excreted. Fick and Wislicenus,3 Frank- land,4 and Haughton 5 have attempted to show that this is 1 SPECK, Ueber die Wirkung der bis zur Ermudung gesteigerten korperlichen Austrengung unter verschiedenen Verhaltnissen auf den Stoffwechsel. — Archiv zur Forderung der wissenschaftlichenHeilkunde, Gottingen, 1860, Bd. iv., S. 591. 2 PARKES, The Composition of the Urine, London, 1860, p. 85, et scq. Dr. Parkes has made some interesting observations, since the publication of his work on the urine, upon the influence of muscular exercise, under a non- nitrogenous diet, upon the elimination of urea. He found the amount of nitrogen in the excreta slightly increased over the amount eliminated during a period of rest, on the same diet The elimination by the skin and intestines was taken into account in these experiments. PARKES, On tJie Elimination of Nitrogen by the Kidneys and Intestines, during Rest and Exercise, on a Diet without Nitrogen. — Proceedings of the Royal Society, London, 1867, vol. xv., Xo. 89, p. 339, et seq. 3 FICK AND WISLICENUS, On the Origin of Muscular Power. — London, Edin- burgh and Dublin Philosophical Magazine, London, Jan.-June, 1866, vol. xxxi., p. 485, et seq. 4 FRANKLAND, On the Origin of Muscular Power, Ibid, July-Dec., 1866, vol. xxxii., p. 182, et seq. 5 HAUGHTON*, Address on the Relation of Food to Work done by the Body, and its Bearing upon Medical Practice. — The Lancet, London, Aug. 15, Aug. 22, and Aug. 29, 1868. EXCRETION. the fact, and have come to the conclusion that muscular force involves chiefly the consumption of non-nitrogenous principles and the production of carbonic acid. While the experiments on this subject have been so meagre, it would be unprofitable to enter into an elaborate discussion of their merits, particularly as they have not been directed specially to the influence of exercise upon the composition of the urine, but to the amount of muscular power developed by different kinds of food. This subject has not been reduced to such an absolute certainty that we are able to calculate mathematically the heat-units, the digestion-coefficients, and the amount of " work " produced by any given quantity of food ; and such calculations cannot, as yet, take the place of actual experimental observations. What we want to know is the measurable influence of muscular exercise upon the proportion of certain of the constituents of the urine, under normal alimentation, every other modifying condition being taken into account. There can be no doubt that, with ordi- nary mixed diet, the elimination of urea is increased by exer- cise. Fick and Wislicenus made their observations, extend- ing over a period of between one and two days, under a diet of non-nitrogenized matter ; and Prof. Haughton compared his observations, made in July, with an average of experi- ments made at different seasons, taking no account of the action of the skin. It may be true that, with a purely non- nitrogenous diet, exercise fails to increase the quantity of urea eliminated by the kidneys, as appears from the observa- tions of Fick and Wislicenus ; but further experiments are necessary to settle even this point ; and recent observations by Parkes show that this is not always the case.1 With regard to the influence of muscular exercise upon the other constituents of the urine, experiments are some- what contradictory. Sometimes the water is lessened, and sometimes it is increased ; this probably depending upon the activity of the cutaneous exhalation. Sometimes the uric 1 See page 227, note. VARIATIONS IN THE TJEINE. 229 acid is increased, and sometimes diminished. The sulphates, phosphates, and chlorides are generally increased. The general result of experimental observations on the effects of exercise upon the urine may be summed up in the proposition that this condition increases the activity of the nutritive processes, and produces a corresponding activity in the function of disassimilation, as indicated by the amount of excrementitious matters separated by the kidneys.1 Influence of Mental Exertion. — Although the influence of mental exertion upon the composition of the urine has not been very much studied, the results of the investigations which have been made upon this subject are, in many re- gards, quite satisfactory. It is a matter of common remark that the secretion of urine is very often modified to a very great extent through the nervous system. Fear, anger, and various violent emotions sometimes produce a sudden and co- pious secretion of urine containing a large amount of water, and this phenomenon is very often observed in cases of hys- teria. Yery intense mental exertion will occasionally pro- duce the same result. We have often observed a frequent desire to urinate during a few hours of intense and unre- mitting mental labor; and on one occasion, being struck with the amount of urine voided, it was found, on exami- nation, to present scarcely any acidity and a specific gravity of about 1002. The interesting point in this connection, however, is to observe the influence of mental labor upon 1 Dr. J. C. Draper made, in 1856, a number of observations upon the effect of exercise on the excretion of urea, from which he concluded that rest does not diminish this excretion, and that exercise does not increase, but actually lessens, the quantity discharged. These conclusions are arrived at by compar- ing the amount of urea excreted by a patient confined to the bed with a frac- tured leg, with the average of eighteen observations upon other persons. The necessary experimental conditions are no better fulfilled in the other observa- tions than in this, and the conclusions arrived at cannot therefore be accepted, in opposition to the accurate experiments of other observers (DRAPER, 7s Mus- cular Motion the Cause of tJie Production of Urea ? — New York Journal of Medi- cine, 1856, New Series, vol. xvi., p. 155, et seg.). 230 EXCKETION. the elimination of solid matters, as contrasted with the amount of excretion during complete repose, the condi- tions of alimentation in the two instances being identical. The most extended series of observations upon this sub- ject, in which all the necessary experimental conditions were fulfilled, are those of Prof. Hammond. These experiments commenced with a standard series of observations, under fixed conditions of diet, exercise, etc., extending over a period of ten days. With a view, then, of determining the influence of increased mental exertion, the number of hours in the day appropriated to study was doubled, the conditions of food and exercise remaining the same as in the standard series. The average of a series of observations, extending over ten days, showed an increase in the quantity of the urine, and an increase, also, in the quantity of all of its solid constituents, with the exception of uric acid, the proportion of which was notably diminished. The amount of variation was as follows : Average of ten days in the standard series : Quantity of urine, 37*95 oz. ; urea, 671*32 grains; uric acid, 14*44 grains ; chlorine, 154'29 grains ; phosphoric acid, 43*66 grains ; and sulphuric acid, 38*47 grains. Average of ten days with increased mental exertion : Quantity of urine, 43*56 oz. ; urea, 749*33 grains ; uric acid, 10*75 grains ; chlorine, 172*62 grains ; phosphoric acid, 66*15 grains ; sulphuric acid, 49*05 grains. In another series of experiments, also extending over ten days, in which there was absence, as far as practicable, of mental exertion, the quantity of urine was diminished, and there was a decrease in the proportion of all of its solid con- stituents.1 These interesting observations have since been confirmed by a number of different series of experiments ; 3 and in a 1 HAMMOND, Urological Contributions. — American Journal of the Medical Sci- ences, Philadelphia, 1856, New Series, vol. xxxi., p. 330, etseq., and Physiological Memoirs, Philadelphia, 1863, p. 17, etseq. 2 THUDICHUM, A Treatise on the Pathology of the Urine, London, 1858, pp. 163, 164. VARIATIONS IN THE URINE. 231 very interesting work upon the influence of cerebral activity upon the composition of the urine, by Byasson, they have been somewhat extended. Byasson found that by mental exertion the quantity of urine was increased ; the amount of urea was also increased; the phosphoric acid was in- creased about one-third ; the sulphuric acid was more than doubled ; and the chlorine was nearly doubled.1 These facts have an important bearing upon our knowl- edge of the effects of mental exertion upon the process of disassimilation of the nervous tissue. They show that nearly all of the solid principles contained in the urine are in- creased in quantity by prolonged intellectual exertion, but they fail to point to any one excrementitious principle, either organic or inorganic, which is specially connected with the physiological wear of the brain. It has been assumed that elimination of the phosphates, increased out of proportion to the increase of the other solid matters of the urine, is one of the constant effects of intellectual effort ; but this view is not sustained by direct physiological experiments, nor by facts in pathology. We have already discussed this question somewhat elaborately, under the head of the phosphates of the urine.8 1 BYASSOX, Essai sur la relation qui existe d fetal physiologique entre Vactivite c'er'dbrale et la composition des urines, Paris, 1868, p. 48, Table. 8 See p. 215. CHAPTEE VIII. PHYSIOLOGICAL ANATOMY OF THE LFVEK. Coverings and ligaments of the liver — Capsule of Glisson — Lobules — Branches .of the portal vein, the hepatic artery and duct — Interlobular vessels — Lob- ular vessels — Origin and course of the hepatic veins — Interlobular veins — Structure of a lobule of the liver — Hepatic cells — Arrangement of the bile-ducts in the lobules — Anatomy of the excretory biliary passages — Vasa aberrantia — Gall-bladder — Hepatic, cystic, and common ducts — Nerves and lymphatics of the liver — Mechanism of the secretion and dis- charge of bile — Secretion of bile from venous or arterial blood — Quantity of bile— Variations in the flow of the bile — Influence of the nervous sys- tem on the secretion of bile — Discharge of bile from the gall-bladder. THE liver, by far the largest gland in the body, is now known to have several entirely distinct functions ; and one of the most important of these has already been fully con- sidered, in connection with digestion.1 It is true that we know very little with regard to the exact office of the bile in digestion, but that this function is essential to life, there can be no doubt. "We have, however, more positive information with regard to the excrementitious function of the liver and the changes which the blood undergoes in passing through its substance; and the study of these functions is closely connected with the anatomy of the liver and the chemical constitution of the bile. Physiological Anatomy of the Liver. It is unnecessary, in this connection, to dwell upon the ordinary descriptive anatomy of the liver. It is sufficient 1 See vol. ii., Digestion, p. 360, et seq. PHYSIOLOGICAL ANATOMY OF THE LIYEE. 233 to state that it is situated just below the diaphragm, in the right hypochondriac region, and is the largest gland in the body, weighing, when moderately filled with blood, about four and a half pounds. Its weight is somewhat variable, but it is stated by Sappey that in a person of ordinary adi- pose development, its proportion to the weight of the body is about one to thirty.1 In early life, the liver is relatively larger, its proportion to the weight of the body, in' the new- born child, being as one to eighteen or twenty.2 The liver is covered externally by peritoneum, folds or duplicatures of this membrane being formed as it passes from the surface of the liver to the adjacent parts. These consti- tute four of the so-called ligaments that hold the liver in place. The proper coat of the liver is a very thin, but dense and resist- ing fibrous membrane, adherent to the substance of the organ, but detached without much difficulty, and very closely united to the peritoneum. This membrane is of variable thickness at different parts of the liver, being especially thin in the groove for the vena cava. At the transverse fissure it sur- rounds the duct, blood-vessels, and nerves, and penetrates the substance of the organ in the form of a vagina, or sheath, surrounding the vessels and branching with them. This membrane, as it ramifies in the substance of the liver, is called the capsule of Glisson. It will be more fully described in connection with the arrangement of the hepatic vessels. The substance of the liver is made up of innumerable lobules, of an irregularly ovid or rounded form, and about ^5- of an inch in diameter. The space which separates these 1 SAPPEY, Traite cFanatomie descriptive, Paris, 1857, tome ii., p. 261. Sappey made a number of examinations of the weight of the normal liver, with the ves- sels moderately distended with water, in order to represent, in a measure, its physiological condition. He estimated the weight from the average of ten liv- ers, taken from both sexes and at different ages after adult life, at two kil., or about four and a half pounds. The weight of the liver with the vessels empty is about three and one-third pounds. 2 WILSON, Cyclopaedia of Anatomy and Physiology, London, 1839-47, vol. iii., p. 178, Article, Liver. EXCRETION. lobules is about one-quarter of the diameter of the lobule, and is occupied with the blood-vessels, nerves, and ramifica- tions of the hepatic duct, all enclosed in the fibrous sheath. In a few animals, as, for example, the pig and the polar-bear, the division of the hepatic substance can be readily made out with the naked eye ; but in man and in most of the mammalia, the lobules are not so distinct, though their ar- rangement is essentially the same. Although the lobules are intimately connected with each other from the fact that branches going to a number of different lobules are given off from the same interlobular vessels, they are sufficiently dis- tinct to represent, each one, the general anatomy of the secreting substance of the liver ; but before we study the minute structure of the lobules, it will be convenient to fol- low out the course of the vessels and the duct, after they have penetrated at the transverse fissure. In this descrip- tion we will follow, in the main, the observations of Iviernan, who has given, probably, the most accurate account of the vascular arrangement in the liver.1 At the transverse fissure, the portal vein, collecting the blood from the abdominal organs, and the hepatic artery, a branch of the coeliac axis, penetrate the substance of the liver, with the hepatic duct, nerves, and lymphatics, all en- veloped in the fibrous vagina, or sheath, known as the cap- sule of Glisson. The portal vein is by far the larger of the two blood-vessels, and its calibre may be roughly estimated at from eight to ten times that of the artery. The vagina, or capsule of Glisson, is composed of fibrous tissue, in the form of a dense membrane, closely adherent to the adjacent structure of the liver, and enveloping the ves- sels and nerves, to which it is attached by a loose areolar tissue. The attachment of the blood-vessels to the sheath is so loose, that the branches of the portal vein are collapsed when not filled with blood ; presenting a striking contrast 1 KIERXAK, The Anatomy and Physiology of the Liver. — Philosophical Trans- actions, London, 1833, p. 711, et seq. PHYSIOLOGICAL ANATOMY OF THE LIVER. 235 to the hepatic veins, which are closely adherent to the sub- stance of the liver, and remain open when they are cut across. This sheath is prolonged over the vessels as they branch and follows them in their subdivisions. It varies considerably in thickness in different animals. In man and the mammalia generally, it is rather thin, becoming more and more delicate as the vessels subdivide, and is entirely lost before the vessels are distributed in the interlobular spaces. The vessels distributed in, and coming from the liver are the following : 1. The portal vein, the hepatic artery, and the hepatic duct, passing in at the transverse fissure, to be distributed in the lobules. The blood-vessels are continuous in the lob- ules with the radicles of the hepatic veins. The duct is to be followed to its branches of origin in the lobules. 2. The hepatic veins ; vessels that originate in the lo- bules, and collect the blood distributed in their substance by branches of the portal vein and hepatic artery. Branches of the Portal Yein, the Hepatic Artery and Duct. — These vessels follow out the branches of the capsule of Glisson, become smaller and smaller, and finally pass directly between the lobules. In their course, however, they send off lateral branches to the sheath ; and those who follow exactly the description of Kiernan, call this the vagi- nal plexus. The arrangement of the vessels in the sheath is not in the form of a true anastomosing plexus, although branches pass from this so-called vaginal plexus between the lobules. These vessels, according to Sappey, do not anasto- mose or communicate with each other in the sheath.1 The portal vein does not present any important pecu- liarity in its course from the transverse fissure to the inter- lobular spaces. It subdivides, enclosed in its sheath, until its small branches go directly between the lobules, and in 1 SAPPEY, Traite cT anatomic descriptive, Paris, 1857, p. 288. 236 EXCRETION. its course it sends branches to the sheath (vaginal vessels), which afterward go between the lobules. The distribution of the hepatic artery, however, is not so simple. This vessel has three sets of branches. As soon as it enters the sheath with the other vessels, it sends off minute branches (vasa vasorum), to the walls of the portal vein, the larger branches of the artery itself, the walls of the hepatic veins, and a very rich net-work of branches to the hepatic duct. When the hepatic artery is completely injected, the walls of the hepatic duct are seen almost covered with vessels. In its course, the hepatic artery also sends branches to the capsule of Glisson (capsular branches), which join with the branches of the portal vein to form the so-called vaginal plexus. From these vessels a few arterial branches are given off and pass between the lobules. The hepatic artery cannot be followed beyond the interlobular spaces. According to Kol- liker and others, the terminal branches of the hepatic artery do not open into the radicles of the hepatic veins, but into small branches of the portal vein, within the capsule of Glisson.1 The hepatic duct follows the general course of the portal vein ; but its structure and relations are so important and intricate that they will be described separately. Interlobular Vessels. — Branches of the portal vein, com- ing from the terminal ramifications as the vessel branches within the capsule and the branches in the walls of the cap- sule, are distributed between the lobules, constituting the greatest part of the so-called interlobular plexus. These are situated between the lobules and surround them ; each ves- sel, however, giving off branches to two or three lobules, and never to one alone. They do not anastomose, and conse- quently do not constitute a true plexus. The diameter of these interlobular vessels varies from I414o to ^-^ of an inch.2 In this distribution, the blood-vessels are followed 1 KOLLIKER, Handbuch der Gewebelehre des Menscken, Leipzig, 1867, S. 443. 2 KOLLIKER, op. cit.t 1867, S. 441. PHYSIOLOGICAL ANATOMY OF THE LITER. 237 by branches of the duct, much less numerous and smaller, measuring only ^soo °^ an mcn ? and some, even, have been measured that are not more than 3^ of an inch in diam- eter.1 Lobular Vessels. — In the interlobular plexus, the ramifi- cations of the hepatic artery are lost, and this can no longer be traced as a distinct vessel. One of the peculiarities of its arrangement, as we have seen, is that the artery 'does not empty into the radicles of the efferent vein, but joins the portal vessels as they are about to be distributed in a true capillary plexus in the substance of the lobules. In the lob- ules themselves, consequently, we have only to study the arrangement of the portal plexus, with the mode of origin of the hepatic veins and the relations of the hepatic duct. The arrangement of the lobular plexus of blood-vessels is very simple. From the interlobular veins, a number of branches (eight to ten) are given off and penetrate the lobule. As the interlobular vessels are situated between different lobules, each one sends branches into two and sometimes three of these lobules ; so that, as far as vascular supply is concerned, these divisions of the liver are never absolutely distinct. After passing from the interlobular plexus into the lobules, the vessels immediately break up into a close net- work of capillaries, from -g-^ to ^Vrr °f an incn *n diame- ter,3 which occupy the lobules with a true plexus. These vessels are very numerous; and when they are fully dis- tended by artificial injection, their diameter is greater than that of the intervascular spaces. It must be remembered, however, that in the study of the liver by minute injections, as in other parts, the vessels probably are distended so that they occupy more space than they ever do under the physio- logical conditions of the circulation. The blood, having been 1 BEALE, On some Points in the Anatomy of the, Liver of Man and Vertebrate Animals, London, 1856, p. 58. 2 KOLLIKER, op. tit., 1867, S. 442. 238 EXCKETKW. distributed in the lobules by this lobular plexus, is collected by venous radicles of considerable size into a single central vessel in the long axis of the lobule, called the intralobular vein. A single lobule, surrounded with an interlobular vessel, showing the lobular capillary plexus, and the central vein (the intralobular vein) cut across, is represented in Fig. 9. FIG. 9. Transverse section of a single hepatic lobule. 1, Intralobular vein, cut across ; 2, 2, 2, 2, Afferent branches of the intralobular vein : 8, 3, 3, 3, 3, 3, 3, 3, 3, Interlobnlar branches of the portal vein— with its capillary branches, forming the lobular plexus, extending to the radicles of the intralobular vein. (SAPPEY. Traite d'anatomie, Paris, 1857, tome iii., p. 297.) With regard to the mode of origin of the hepatic duct in the substance of the lobule, recent researches have shown that it begins by a very fine anastomosing plexus of vessels, with amorphous walls, situated between the liver-cells ; but there are many different opinions on this subject, and we will defer its full consideration until we take up the anatomy of the secreting structures in the lobules. Origin and Course of the Hepatic Veins. — The blood distributed in the lobular capillary plexus furnishes the ma- terials for the formation of bile, and undergoes those changes PHYSIOLOGICAL ANATOMY OF THE LIVER. 239 produced by the action of the liver as a ductless gland ; in other words, it is in and around this plexus that all the physiological functions of the liver are performed. It is then only necessary that the blood should be carried from the liver to go to the right side of the heart ; and the ar- rangement of the hepatic veins is accordingly very simple. Intralobular Veins. — The innumerable capillaries of the lobules converge into three or four venous radicles (rep- resented in Fig. 9), which empty into a central vessel, from ToVo- to TFF °f an mcn m diameter.1 This is the intralob- ular vein. If a liver be carefully injected from the hepatic veins, and sections be made in various directions, it will be seen that the intralobular veins follow the long axis of the lobules, receiving vessels in their course, until they empty into a larger vessel, situated at what may be termed the base of the lobules. These vessels have been called, by Kiernan, the sublobular veins. They collect the^ blood in the manner just described from all parts of the liver, unite with others, becoming larger and larger, until finally they form the three hepatic veins, which discharge the blood from the liver into the vena cava ascendens. The hepatic veins differ somewhat in their structure from other portions of the venous system. Their walls are thinner than those of the portal veins ; they are not en- closed in a sheath, and are very closely adherent to the he- patic tissue. It is this provision which makes the force of respiration from the thorax so efficient in the circulation in the liver.2 Here, indeed, a force added to the action of the heart is especially necessary ; for the blood is passing in the liver through a second capillary plexus, having already been distributed in the capillaries of the alimentary canal and other abdominal organs, before it is received into the portal vein. It has also been noted that the hepatic veins possess a well-marked muscular tunic, very thin in man, but well developed in the pig, the ox, and the horse, and composed 1 KOLLIKER, op. cit., 1867, S. 442. 2 See vol. i., Circulation, p. 322. 240 EXCRETION. of unstriped muscular fibres interlacing with each, other in every direction.1 In addition to the blood-vessels just described, the liver receives venous blood from vessels which have been called accessory portal veins, coming from the gastro-hepatic omen- tum, the surface of the gall-bladder, the diaphragm, and the anterior abdominal walls. These vessels penetrate at dif- ferent portions of the surface of the liver, and may serve as derivatives when the circulation through the portal vein is obstructed. Structure of a Lobule of the Liver. — Each hepatic lob- ule, bounded and more or less distinctly separated from the others by the interlobular vessels, contains blood-vessels, radicles of the hepatic ducts, and the so-called hepatic cells. The arrangement of the blood-vessels has just been de- scribed; but in all preparations made by artificial injection, the space occupied by the blood-vessels is exaggerated by excessive distention, and the difficulties in the study of the relations of the ducts and the liver-cells are thereby much increased. Under any conditions, there are few questions, if any, in minute anatomy, that are so complicated as that of the origin of the bile-ducts in the lobules. If we were to attempt a critical analysis of the important investigations made upon this subject during the last thirty-five years, we would only illustrate the great diversity of opinion among eminent authors upon difficult anatomical questions. As the important problem in the minute anatomy of the lobules has been the relations of the cells to the radicles of the bile- ducts, we will first take up the structure of the cells. Hepatic Cells. — If a scraping from the cut surface of a fresh liver be examined with a moderately high magnifying power, the field of view will be found filled with numerous rounded, ovoid, or irregularly polygonal cells, measuring from rsW to TTOT °f an mch m diameter. In their natural con- 1 SAPPEY, op. cit., p. 300. PHYSIOLOGICAL AST ATOMY OF THE LIVER. dition, they are more frequently ovoid than polygonal, and when they have the latter form, the corners are always rounded. These cells present one and sometimes two nu- clei, sometimes with and sometimes without nucleoli. The presence of numerous small pigmentary granules gives to the cells a peculiar and characteristic appearance ; and, in addition, nearly all of them contain a few granules or small globules of fat. Sometimes the fatty and pigmentary mat- ter is so abundant as to obscure the nuclei. The addition of acetic acid renders the cells pale and the nuclei more dis- tinct. By appropriate reagents, animal starch (probably glycogenic matter) has been demonstrated in the substance of the cells.1 Arrangement of the Bile-ducts in the Lobules. — Before the publication of the researches of Kiernan, no reasonable speculations, even, had been made with regard to the ulti- mate arrangement of the bile-ducts. Kiernan supposed that the lobules contained a reticulated net-work of ducts com- municating with the ducts in the interlobular spaces ; but he only inferred their existence, and his figures, which have been extensively copied, are merely diagrammatic.2 The same arrangement essentially was described by Prof. Leidy> who figures a net-work of canals in the lobules, lined with the liver-cells ; but the evidence in favor of this view is not convincing.3 The results of the researches of Beale were at one time adopted by many anatomists. Beale supposed that there existed in the lobules delicate tubes, about as wide as the liver-cells, each tube enclosing a row of these cells.4 The presence of this delicate membrane, however, 1 SCHIFF, De la nature des granulations qui remplissent les cellules hepatiques : Amidon animate. — Comptes rendus, Paris, 1859, tome xlviii., p. 880. 2 KIERXAN, op. cit. — Philosophical Transactions, London, 1833, p. 711, ft seq. 3 LEIDY, Researches into the Comparative Structure of the Liver. — American Journal of the Medical Sciences, Philadelphia, 1848, Xew Series, vol. xv., p. 13, el seq. 4 BEALE, On some Points in the Anatomy of the Liver of Man and Vertebrate Animals, London, 1856, p. 73. 16 24:2 EXCRETION. was not satisfactorily demonstrated. Kolliker formerly ac- cepted in part the views advanced by Beale ; but his ideas upon this subject, in all but the last edition of his work, have not been very definite.1 Such is the condition of the question of the origin of the biliary ducts, as it is understood by most English and Amer- ican authors; and although the above statement does not represent all the views entertained by different anatomists, it is sufficient to show the exceedingly indefinite condition of the whole subject. Kolliker, indeed, in a letter to Dr. Sharpey, of London (1867), and in the last edition of his work on histology, abandons his former views, and states that he has become fully convinced of the accuracy of recent observations which lead to an entirely new description of the bile-ducts ; a and Prof. Leidy, in his work on anat- omy, published in 1861, does not commit himself to any definite opinion on the subject.3 Late researches have shown that the following is probably the true relation of the ultimate ramifications of the bile-ducts in the lobules to the hepatic cells : In the substance of the lobules is an exceedingly fine and regular net- work of vessels, of uniform size, about 10}00 of an inch in diameter,4 which surround the liver-cells, each cell lying in a space bounded by inosculating branches of these canals. This plexus is entirely independent of the 1 KOLLIKER, Manual of Human Microscopic Anatomy, London, 1860, p. 346. 2 Journal of Anatomy and Physiology, Cambridge and London, 1868, vol. ii., p. 163. These views have been adopted by Kolliker in the last edition of his work on Microscopic Anatomy (Handbuch der Gewcbelehre, Leipzig, 1867, S. 428). 3 LEIDY, An Elementary Treatise on Human Anatomy, Philadelphia, 1861, p. 327. 4 This is the result of the measurements by Dr. Stiles (Bulletin of tJie New York Academy of Medicine, 1868, vol. iii., p. 351), of the ducts in the livers of the bullocks that died of the " Texas disease," which we have verified in the same specimen. The measurements given by Frey are about the same (Hand- buch der Histoloaic, Leipzig, 1867, a 558). PHYSIOLOGICAL ANATOMY OF THE LIVEK. 243 FIG. 10. blood-vessels, and it seems to enclose in its meshes each indi- vidual cell, extending from the periphery of the lobule, where it is in communication with the interlobular bile- ducts, to the intralobu- lar vein in the centre. The vessels probably have excessively thin, homogeneous walls — though the existence of their membrane has not been positively demon- strated— and are with- out any epithelial lin- ing, being much small- er, indeed, than any epithelial cells with which we are acquaint- ed. This arrangement, /. . -, , Portion of a transverse section of an hepatic lo- aS lar as IS KnOWll, naS bule of the rabbit, magnified 400 diameters, ft, capillary blood-vessels; ^, capillary bile-ducts; /. liver-cells. (KQLLIKER, Handbuch der Gfeuxte- lehre des Mewchen, Leipzig, 1867, S. 428.) no analogue in any other secreting organ. Although it is within three or four years only that the reticulated bile-ducts of the lobules have attracted much attention, they were discovered in the substance of the lobules, near the periphery, by Gerlach, in 1848.1 It is evi- dent, from an examination of his figures and description, that he succeeded in filling with injection that portion of the lobular network near the borders of the lobules, and demonstrated the continuity of their vessels with the inter- lobular ducts ; but he did not recognize the vessels nearer the centre of the lobule. His views, however, received very little attention, and are not even mentioned in most of the authoritative works on general anatomy. Within the last 1 GERLACH, Handbuch der allgemeinen und speddlen Gewebekhre, Mainz, 1848, S. 280, et seq. 24:4 EXCRETION. few years, Budge,1 Andrejevic,2 Mac-Gillavry,3 Chrzonszc- zewsky,4 Wyss,5 Hering,6 Frey,7 Eberth,8 Kolliker,9 and others have investigated this interesting question, by vari- ous methods, and have arrived at the most positive and satis- factory results. It is now demonstrated, beyond a doubt, that there are either canals or interspaces between the liver-cells in the lobules, and that these open into the in- terlobular hepatic ducts. It is still a question of discussion, whether these passages are simple spaces between the cells, or are lined by a membrane ; but this point has no great physiological importance, and we can readily imagine that it would be exceedingly difficult to demonstrate a membrane forming the wall of a tube, the whole measuring but 10^00 of an inch. In the investigations which have thus demon- strated the arrangement of the finest bile-ducts in the lobules, the livers of rabbits have been found to present the most favorable conditions. It has been assumed, however, that in the method of study by artificial injection, the ap- pearance of canals might be due to the extravasation of the fluid, which might possibly take on a regular arrangement between the cells. This is an error of observation that would not be unlikely to occur ; but not only have these fine 1 BUDGE, Ueber den Verlauf der Gallengdnge. — Archiv fur Anatomic, Physi- ologic und wissenschaftlichen Medicin, Leipzig, 1859, S. 642, et seq. 2 ANDRE jEVi6, Ueber denfeineren Bau der Leber. — SitzungsbericMe der mathe- matisch-naturwissenschaftlichen Classe der Kaiserliclien Akademie der Wissen- schaften, Wein, 1861, Bd. xliii., I. Abtheilung, S. 379, et seq. 3 MAC-GILLAVRY, Zur Anatomie der Leber, Idem, Wein, 1865, Bd. i., II. Abtheilung, S. 207, et seq. 4 CHRZONSZCZEWSKY, Zur Anatomie und Physiologic der Lebcr. — VIRCHOW'S Archiv, Berlin, Jan., 1866, Bd. xxxv., S. 153, et seq. 5 WYSS, Beitrag zur Histologie der icterischen Leber. — VIRCHOW'S Archiv, Ber- lin, April, 1866, Bd. xxxv., S. 553, et seq. 6 BERING, Ueber den Bau der Wirbelthierleber. — Sitzungberichte, etc., Wein, 1866, Bd. liv., I. Abtheilung, S. 335. 7 FREY, Handbuch der Histologie, Leipzig, 1867, S. 557, et seq. 8 EBERTH, Untersuchungen uber die normale und pathologische Leber. — VIR- cnow's Archiv, Berlin, Mai, 1867, Bd. xxxix., S. 70, et seq. 9 KOLLIKER, Handbuch der Gewebelehre, Leipzig, 1867, S. 428. EXCRETORY BILIARY PASSAGES. 2:t5 ducts been filled by injection and their connection with the interlobular ducts apparently established, they have been observed filled with inspissated bile in icteric livers.1 A method of study, very ingenious and highly satisfactory in its results, was adopted by Chrzonszczewsky. He intro- duced into the blood-vessels or stomach of a living animal a solution of indigo-carmine, and within one or two hours, killed the animal, when the whole net-work of ducts in the lobules was found unbroken and connected with the inter- lobular vessels. The drawings of these appearances accom- panying the memoir are exceedingly beautiful.* A peculiarly favorable opportunity for observing the bile-ducts in the lobules was presented in the livers of ani- mals that died of the so-called " Texas cattle-disease." This was taken advantage of by Dr. R. C. Stiles, who was able to verify, in the most satisfactory manner, the facts which have lately been established by the German anatomists.3 In these livers, the finest bile-ducts were found filled with bright yellow bile, and their relations to the liver-cells were beauti- fully distinct. In the examination of these specimens, the presence of what appeared to be detached fragments of these little canals is an argument in favor of the view that they were lined by a membrane of excessive tenuity. These in- teresting anatomical points were demonstrated by Dr. Stiles before the Xew York Academy of Medicine, and we have since been able to verify them in every particular. Anatomy of the Excretory Biliary Passages. — There can be scarcely any doubt of the connection between the in- tercellular biliary plexus in the substance of the lobules and 1 WTSS, loc. cit. 2 Loc. cit. 3 STILES, Bulletin of tJie New York Academy of Medicine, 1868, vol. iii., p. 350 ; Report of the New York State Cattle Commissioners, in connection with the Special Report of the Metropolitan Board of Health on the Texas Cattle-Disease. — Transactions of the New York State Agricultural Society, Albany, 1868, vol. xxvii. — 1867, Part ii., pp. 1137, 1160; and Third Annual Report of the Me- tropolitan Board of Health of the State of New York, Albany, 1868, p. 303. 246 EXCRETION. the interlobular ducts. We shall see, further on, that the ducts, in their course from the lobules to the intestine, are provided with numerous small racemose glands, which prob- ably secrete a mucus that is mixed with the bile ; but, in all probability, the peculiar elements of the bile are formed in the lobules, and the canals situated between the lobules and leading from them to the larger ducts are merely excre- tory. Between the lobules the ducts are very small, the smallest measuring about -^-gVo" °f an ^ncn m diameter. They are composed of a delicate membrane, lined with small, flat- tened epithelium. According to Robin, the cells lining the excretory ducts are ciliated ; l but this is not the view gener- ally adopted. The ducts larger than 12100 of an inch have a fibrous coat, formed of inelastic, with a few elastic ele- ments, and in the larger ducts there are, in addition, a few non-striated muscular fibres. The epithelium lining these ducts is of the columnar variety, the cells gradually under- going a transition from the pavement form as the ducts in- crease in size. In the largest ducts there is a distinct mu- cous membrane, with mucous glands. Throughout the whole extent of the biliary passages, from the interlobular canals to the ductus choledochus, are little utricular or racemose glands, varying in size in differ- ent portions of the liver, called, by Robin, the biliary acini. These are situated, at short intervals, by the sides of the canals. The glands connected with the smallest ducts are simple follicles, from -g-J-g- to ^-J-g- of an inch long. The larger glands are formed of groups of these follicles, and measure from -g-J-^ to y^- of an inch in diameter. The glands are only found connected with the ducts ramifying in the substance of the liver, and do not exist in the hepatic, cystic, and common ducts. They are composed of a homogeneous membrane, lined with small, pale cells of pavement-epithe- 1 LITTRE ET ROBIN, Dictionnaire de medecine, Paris, 1865, p. 611, Article, Foie. EXCKETGBY BILIARY PASSAGES. 247 Hum. If the ducts in the substance of the liver be isolated, they are found covered with these little groups of follicles, and have the appearance of an ordinary racemose gland, ex- cept that the acini are relatively small and scattered. This appearance is represented in Fig. 11. FIG. 11. Anastomoses, and racemose glands attached to the biliary ducts of the pig, magnified eighteen diameters. 1. 1. Branch of an hepatic duct, with the surface almost entirely covered with racemose glands opening into its cavity ; 2, Branch in which the glands are smaller and less numerous ; 3, 3, 3, Branches of the duct with still simpler glands: 4. 4. 4, 4. Biliary ducts with simple follicles attached; 5, 5, 5, 5, Same, with 6, Anastomoses in arches ; 7, 7, 7, Angular a fewer follicles ; 6. 6. 6, 6, 6, 8. 8. 8. 8. Anastomoses by transverse branches. 1857, tome iii., p. 279.) anastomoses : (SAPPEY, Traiie tfanaLamie, Paris. The excretory biliary ducts, from the interlobular vessels to the point of emergence of the hepatic duct, present nu- merous anastomoses with each other in their course. Vasa Aberrantia. — In the livers of old person?, and oc- casionally in the adult, certain vessels are found ramifying on the surface of the liver, but always opening into the biliary ducts, which have been called vasa aberrantia. These are never found in the foetus or in children. They are, un- doubtedly, appendages of the excretory system of the liver, and are analogous in their structure to the ducts, but are 248 EXCRETION. apparently hypertrophied, with thickened, fibrous walls, and present, in their course, irregular constrictions, not found in the normal ducts. The racemose glands attached to them are always very much atrophied. Sappey is of the opinion that these are ducts leading to lobules on the surface of the liver which have become atrophied.1 Gall-bladder, Hepatic, Cystic, and Common Ducts. — The hepatic duct is formed by the union of two ducts, one from the right and the other from the left lobe of the liver. It is about an inch and a half in length, and joins at an acute angle with the cystic duct, to form the ductus commu- nis choledochus. The common duct is about three inches in length, of the diameter of a goose-quill, and opens into the descending portion of the duodenum. It passes obliquely through the coats of the intestine, and opens into its cavity in connection with the principal pancreatic duct. The cys- tic duct is about an inch in length and is the smallest of the three canals. The structure of these ducts is essentially the same. They have a proper coat, formed of white fibrous tissue, a few elastic fibres, and a few non-striated muscular fibres. The muscular tissue is not sufficiently distinct to form a separate coat. The mucous membrane is always found tinged yellow with the bile, even in living animals. It is marked by numerous minute excavations, and is covered with cells of columnar epithelium. This membrane con- tains numerous mucous glands. The gall-bladder is an ovoid or pear-shaped sac, about four inches in length, one inch in breadth at its widest por- tion, and capable of holding from an ounce to an ounce and a half of fluid. Its fundus is covered entirely with peri- toneum, but this membrane passes only over the lower sur- face of the body. The proper coat of the gall-bladder is composed of white fibrous tissue with a few elastic fibres. In some of the lower 1 SAPPEY, op. cit., tome iii., p. 283. XERVE3 AND LYMPHATICS OF THE LIVER. 249 animals there is a distinct muscular coat, but a few scattered fibres only are found in the human subject. The mucous coat is of a yellowish color, and marked with numerous very small, interlacing folds, which are exceedingly vascular. Like the membrane of the ducts, the mucous lining of the gall-bladder is covered with columnar epithelium. In the gall-bladder are found numerous small racemose glands, formed of from four to eight follicles lodged in the submu- cous structure. These are essentially the same as the glands opening into the ducts in the substance of the liver, and secrete a mucus, which is mixed with the bile. Nerves and Lymphatics of the Liver. — The nerves of the liver are derived from the pneumogastric, the phrenic, and the solar plexus of the sympathetic. The branches of the left pneumogastric penetrate with the portal vein, while the branches from the right pneumogastric, the phrenic, and the sympathetic surround the hepatic artery and the hepatic duct. All of these nerves penetrate at the transverse fissure and follow the blood-vessels in their distribution. They have not been traced farther than the terminal ramifications of the capsule of Glisson, and their exact mode of termination is unknown. The lymphatics of the liver are very numerous. They are divided into two layers : the superficial layer, situated just beneath the serous membrane; and the deep layer, formed of a plexus surrounding the lobules and situated outside of the blood-vessels. The superficial lymphatics from the under surface of the liver, and that portion of the deep lymphatics which follows the hepatic veins out of the liver, pass through the diaphragm and are con- nected with the thoracic glands. Some of the lymphatics from the superior or convex surface join the deep vessels that emerge at the transverse fissure, and pass into glands below the diaphragm, while others pass into the thoracic cavity. 250 EXCRETION. Mechanism of the Secretion and Discharge of Bile. — The liver lias no analogue in the glandular system, either in its anatomy or its physiology. There is no gland in the economy which we know to have two distinct functions, such as the secretion of bile, and the production of certain elements destined to be taken up by the current of blood as it passes through. In other words, there is no organ in the body which has at the same time the functions of an or- dinary secreting gland and a ductless gland. If we regard the liver-cells as the anatomical elements which prodiice the bile, it is evident that their number is very much out of pro- portion to the amount of bile secreted ; and the liver itself is an organ of much greater size than it seems to us would be required for the mere secretion of bile. "We explain this disproportionate size by the fact that the liver has other functions as a ductless gland. There is no gland in which the arrangement of secreting tubes is the same as in the liver. It is hardly possible that the intercellular plexus of fine tubes in the lobules should be any thing but the plexus of origin, or the secreting portion of the hepatic duct. These are certainly not blood-vessels, and the only vessels that could have the appearance we have described, except the bile-ducts, are the lymphatics ; but the communication between these vessels and the excretory bile- ducts, and the fact that they have been seen distended with bile in icteric livers, are pretty conclusive evidence of their nature. This arrangement, then, must be regarded as pe- culiar to the liver, as the arrangement of a capillary plexus, surrounded with cells and enveloped in a dilated extremity of a secreting tube, is peculiar to the kidney and is found in no other glandular organ. Do the liver-cells, situated outside of the plexus of origin of the biliary duct, secrete the bile, which is taken up by these delicate vessels and carried to the excretory biliary pas- sages ? There are very good reasons for answering this ques- tion in the affirmative ; though, if we do, we must recognize MECHANISM OF THE SECRETION OF BILE. " 251 the fact that the same cells produce glycogenic matter. As far as. we are able to understand the mechanism of secretion, it seems necessary that a formed anatomical element, known as a secreting cell, should elaborate, from materials furnished by the blood, the elements of secretion ; and this cannot be accomplished by a structureless membrane, like that which forms the walls of the bile-ducts.1 Under this view, assum- ing that bile, as bile, first makes its appearance in these little lobular tubes, the liver-cells are the only anatomical elements capable of producing the secretion. With regard to the mechanism of this secreting action, we have nothing to say beyond our general remarks in the first chapter. With the view we have just expressed, certain elements of the bile are separated from the blood, and others are manu- factured out of materials furnished by the blood by the liver-cells, and are taken up by the delicate plexus of vessels situated between the cells. The discharge of the fluid is like the discharge of any other of the secretions, except that a portion is temporarily retained in a diverticulum from the main duct, the gall-bladder. The two distinct functions of the liver now recognized by many physiologists, namely, the secretion of bile and the formation of sugar, have led to the question of the ex- istence in the liver of two anatomically distinct portions or organs, corresponding to its double physiological func- tion. This view, indeed, has been advanced by several eminent anatomists. Robin recognizes two distinct parts in the liver ; a biliary organ and a glycogenic organ. He regards the lobules, with their liver-cells and blood-vessels, as the parts concerned in the glycogenic function of the liver, and the little glands which open into the biliary ducts all along their course (see Fig. 11) and are arranged on the duct "in the form of leaves of fern," as the biliary 1 An exception to this rule is in the secretion of milk during the period of greatest activity of the mammary glands. (See p. 79.) 252 EXCRETION. organ.1 The same independence of the glycogenic and bil- iary portions of the liver has been argued by others. Among the latest publications on this subject is a review of the question by Accolas ; 3 but although this was published in 1867, there is no mention of the late researches, to which we have referred so fully, on the origin of the ducts in the lobules. The fact of bile being found in the lobular canals and the demonstration of the direct communication of these canals with the excretory biliary ducts are powerful ar- guments in favor of the view that the bile is formed in the lobules, and probably by the liver-cells. What, then, is the function of the little acini connected exclusively with the biliary ducts ? The similarity of their structure to that of the ordinary mucous glands, and to the mucous glands of the gall-bladder especially, would lead to the supposition that they secrete a mucous fluid. It is well known that the bile taken from the gall-bladder contains more mucus than that discharged directly from the liver ; but the bile of the he- patic duct in most animals is somewhat viscid and contains a certain amount of mucus. This is the view entertained by Sappey, who states that the bile is viscid in different animals in proportion to the development of these little glands ; and in the rabbit, in which the glands do not exist, the bile is remarkably fluid.3 Inasmuch as there is no direct evidence that the racemose glands attached to the excretory biliary passages have any thing to do with the secretion of the essential constituents of the bile, and as they are not even to be found in some animals that produce a considerable quantity of bile, we must regard the question of the isolation of two organs in 1 LITTRE ET ROBIN, Dictionnaire de medecine, Paris, 1865, p. 611, Article, Foie, and Lemons sur les humeurs, Paris, 1867, p. 551, et seq. 2 ACCOLAS, Essai sur Vorigine des canalicules hepatiques et sur I 'independance des appareils biliaire et glycogene dufoie, Strasbourg, 1867. 3 SAPPEY, Traite d1 anatomic descriptive, Paris, 1857, tome iii., p. 280. MECHANISM OF THE SECRETION OF BILE. 253 the liver, one for the secretion of bile and the other for the production of sugar, as still unsettled. There is no evi- dence, indeed, that the bile is secreted anywhere but in the hepatic lobules. Secretion of Bile from Venous or Arterial Blood. — Xumerous experiments have been made with the. view of determining whether the bile be secreted from the blood brought to the liver by the portal vein, or from the blood of the hepatic artery. The immense quantity of blood distrib- uted in the liver by the portal vein led first to the opinion that the impurities were separated from this blood to form the bile, and that the hepatic artery had little or nothing to do with the secretion. This, indeed, was the view adopted by Glisson,1 one of the earliest writers on the anatomy and functions of the liver. But since Bernard discovered the glycogenic function of the liver, this subject has assumed additional importance ; and it becomes a question whether the materials for the secretion of bile may not be furnished by one vessel (the hepatic artery), while the other (the portal vein) is specially concerned in the formation of glycogenic matter. This theoretical view, however, is not carried out by well-established anatomical facts or by physiological ex- periments. It is not yet possible to separate the liver ana- tomically into two organs, one for the secretion of bile and the other for the production of sugar. It seems certain, also, from numerous experiments,3 that bile may be secreted from the blood of the portal vein after a ligature has been applied to the hepatic artery ; and it is equally certain, from the re- cent experiments of Ore,8 that, if the portal vein be obliter- ated so gradually that the animal does not die from the op- eration, bile is secreted from the blood of the hepatic artery. 1 GLISSOXIUS, Anatomia Hepatis, London, 1654, p. 383. 2 LOXGET, Traite de physiologic, Paris, 1869, tome ii., p. 305. 3 ORE, Influence de V obliteration de la veine porte *ur la secretion de la bile. — Comptesrendus, Paris, 1856, tome xliii., p. 463. 254 EXCRETION. The experiments of M. Ore are very curious and in- structive. After having repeatedly made the experiment of applying a tight ligature to the portal vein, producing thereby very grave sympt6ms and death so speedily that the effects upon the secretion of bile could not be satisfactorily ob- served, he modified his operations so as to effect a gradual obliteration of the vein. This he accomplished by simply applying a loose ligature, and tightening it from time to time until it came away. By this mode of procedure he suc- ceeded in observing the secretion of bile six days or more after the application of the ligature ; and, on killing the animals, he found the portal vein entirely obliterated and no communicating branches by which the blood could get from the portal system to the liver. From these observa- tions it is concluded that the bile is secreted from the blood of the hepatic artery. In support of this view, several instances of obliteration of the portal vein in the human subject are cited in works upon physiology. In a note to the communication of Ore in the Comptes rendus, Andral reports the case of a patient that died of dropsy, and on post-mortem examination the portal vein was found obliterated. In this instance the gall- bladder was found full of bile.1 In addition, instances in which the portal vein emptied into the vena cava have been reported,2 and in none was there any deficiency in the secre- tion of bile. If the experiments upon the effects of tying the hepatic artery, and the observations of instances of obliteration of the portal vein and of congenital malformation, in which the portal vein does not go to the liver, be equally reliable, there 1 Comptes rendus, Paris, 1856, tome xliii., p. 46*7. 2 ABERNETHT, Account of two Instances of Uncommon Formation, in the Viscera of the Human Body, — Philosophical Transactions, London, 1793, p. 59. LAWRENCE, Account of a Child born without a Brain, which lived four Days ; with a sketch of the principal deviations from the ordinary Formation of the Body ; Remarks on their Production, and a view of some Physiological Inferences to which they lead. — Medico- Chirurgical Transactions, London, 1814, vol. v., p. 174. QUANTITY OF BILE. 255 is but one conclusion to be drawn from them ; and that is, that bile may be secreted from either venous or arterial blood. This view is not inconsistent with what we know of the general process of secretion and its applications to the production of bile. Regarding the bile as in part an excrementitious fluid, its effete element — cholesterine — is contained both in the blood of the portal vein and in the he- patic artery. Its recrementitious principles — glycocholates, taurocholates, etc. — we suppose are produced de novo in the liver, out of materials furnished by the blood. The exact nature of the production of elements of secretion by glandular cells we do not understand ; but there is no good reason to suppose that the principles necessary for the for- mation of bile may not be furnished by the blood of the portal vein, as well as by the hepatic artery. The view most nearly in accordance with all the facts bearing on the question is, that bile is produced in the liver from the blood distributed in its substance by the portal vein and the hepatic artery, and not from either of these vessels exclusively ; and that the bile may continue to be se- creted, if either one of these vessels be obliterated, provided the supply of blood be sufficient. Quantity of JSile.^-The estimates of the daily quantity of bile in the human subject must be merely approximative ; and our only ideas on this point are derived from experi- ments upon the inferior animals. The most complete and reliable observations on this subject are those of Bidder and Schmidt, and were made upon animals with a fistula into the gall-bladder, the ductus conimunis having been tied.1 These observers found great variations in the daily quantity in dif- ferent classes of animals, the quantity in the carnivora being the smallest. Applying their results to the human subject, assuming that the amount is about equal to the quantity secreted by the carnivora, the daily secretion in a man 1 BIDDER UND SCHMIDT, Die Verdauungssafte, Leipzig, 1852, S. 209. 256 EXCRETION. weighing one hundred and forty pounds would be about two and a half pounds.1 Variations in the Flow of the Bile. — We have already considered, in another section, the variations in the flow of bile, and their relation to the process of intestinal digestion.8 It is sufficient in this connection to repeat that the discharge from a biliary fistula in a dog increases immediately after eating ; that it is at its maximum from the second to the eighth hour, during which time it does not vary to any great extent ; after the eighth hour it begins to diminish, and from the twelfth hour to the time of feeding, it is at its minimum. Prof. Dalton made observations on the flow of bile from a fistula into the duodenum, which would represent the physi- ological discharge of bile into the intestine more nearly than observations with a biliary fistula. He found that by far the largest quantity passes into the intestines im- mediately after feeding and within the first hour.3 These results agree in all essential particulars with previous obser- vations on this subject — which have been very numerous — and they show that while the bile is discharged much more abundantly during intestinal digestion than during the in- tervals of digestion, its production and discharge are con- stant. This, we shall see in the next chapter, is a strong argument in favor of the view that the liver has an excre- mentitious function. The bile is stored up in the gall-bladder to a consider- able extent during the intervals of digestion. If an animal be killed at this time, the gall-bladder is always distended ; 1 This is the estimate adopted by Dalton (Treatise on Human Physiology, Philadelphia, 1867, p. 172). In our own experiments, made on a dog with a biliary fistula, the object was not so much to ascertain the entire quantity of bile in the twenty-four hours as to note the variations in its flow. The estimate was made in a dog that had become somewhat enfeebled, and is undoubtedly too low. (See vol. ii., Digestion, p. 375.) 2 See vol. ii., Digestion, p. 375. 3 DALTON, op. cit., p. 176. DISCHARGE OF THE BILE. 25 T but it is found empty, or nearly so, in animals killed during digestion. The influence of the nervous system upon the secretion of bile has been very little studied, and the question is one of great difficulty and obscurity. The liver is supplied very abundantly with nerves, both from the cerebro-spinal and the sympathetic system, and some observations have been made upon the influence of the nerves on its glycogenic function ; but with regard to the secretion of bile, we can only apply our general remarks concerning the influence of the nervous system on secretion.1 The bile is discharged through the hepatic ducts like the secretion of any other gland. During digestion, the fluid accumulated in the gall-bladder passes into the ductus com- munis, in part by contractions of its walls, and in part, prob- ably, by compression exerted by the distended and congested digestive organs adjacent to it. It seems that this fluid, which is necessarily produced by the liver without inter- mission, separating from the blood certain excrementitious matters, is retained in the gall-bladder for use during digestion. 1 See page 28, et seq. The extent of our knowledge of the influence of the nervous system on the secretion of bile is well presented in the following paragraph : " The nervous system has assuredly a very great influence on the resorption of bile or on an obstacle offered to its discharge ; but we know nothing distinct relative to this action, although we cannot deny it in the face of instances where fear has been sufficient to suddenly produce icterus. The cause of this can only be attributed to the influence of the pneumogastric or the grand sympa- thetic (BERNARD, Liquides de Vorganlsme, Paris, 1859, tome ii., p. 212). 17 CHAPTER IX. EXCRETORY FUNCTION OF THE LIVER. General properties of the bile — Composition of the bile — Biliary salts — Tauro- cholate of soda — Glycocholate of soda — Origin of the biliary salts — Choles- terine — Process for the extraction of cholesterine — Biliverdine — Tests for bile — Test for biliverdine — Test for the biliary salts — Pettenkofer's test — Excretory function of the liver — Origin of cholesterine — Experiments showing the passage of cholesterine into the blood as it circulates through the brain — Analyses of venous blood from the two sides of the body in cases of hemiplegia — Elimination of cholesterine by the liver — Analyses showing accumulation of cholesterine in the blood in certain cases of organic disease of the liver — Cholesteraemia. ALTHOUGH the function of the bile in intestinal digestion is essential to life, we know very little of its mode of action ; and we have thought proper to defer until now a full con- sideration of the properties and composition of this secretion. For an account of what is known of its digestive function, the reader is referred to the section of volume second, treat- ing of digestion. We shall show, in this connection, that the liver excretes one of the most important of the effete princi- ples ; but before taking up the relations of the bile as an ex- cretion, it will be necessary to study its general properties and composition. General Properties of the Bile. — The secretion, as it comes directly from the liver, is somewhat viscid ; but after it has passed into the gall-bladder, its viscidity is much greater from further admixture of mucus. The color of the bile is very variable within the limits PROPERTIES OF THE BILE. 259 of health. It may be of any shade between a dark, yellow- ish green and a reddish brown. It is semitransparent, ex- cept when the color is very dark. In different classes of animals the variations in color are very great. In the pig it is bright yellow ; in the dog it is dark brown ; -and in the ox it is greenish yellow. As a rale, the bile is dark green in the carnivora and greenish yellow in the herbivora. The specific gravity of the human bile, according to Prof. Dalton, is 1018 ; 1 but this is somewhat lower than the aver- age usually given, which is from 1020 to 1026.3 "When the bile is perfectly fresh, it is almost inodorous, but it readily undergoes putrefactive changes. It has an excessively dis- agreeable and bitter taste. It is not coagulated by heat. When mixed with water and shaken, it becomes frothy, probably on account of the tenacious mucus and its sapona- ceous constituents. It is generally stated that the bile is invariably alkaline. This is true of the fluid discharged from the hepatic duct,3 although the alkalinity is not strongly marked; but the reaction varies after it has passed into the gall-bladder. Bernard found it sometimes acid and sometimes alkaline in the gall-bladder, in animals — dogs and rabbits — killed under various conditions ; * but many of these animals were suffering from the effects of severe operations. In the hepatic ducts the reaction is always alkaline ; and there are no observations on human bile that show that the fluid is not alkaline in all of the biliary passages. We have already noted the fact that the epithelium of the biliary passages is strongly tinged with yellow, even in living animals. This is due to the remarkable facility with which the coloring principle of the bile stains the animal tissues. This is very well illustrated in icterus, when even a 1 DALTON, Treatise on Human Physiology, Philadelphia, 1867, p. 159. 2 LONGET, Traite de physiologic, Paris, 1868, tome i., p. 278. 3 ROBIN, Lemons sur les humeurs, Paris, 1867, p. 538. 4 BERNARD, Liquides de forganisme, Paris. 1859, tome ii., p. 212. 260 EXCRETION. small quantity of this coloring matter finds its way into the circulation. Perfectly normal and fresh bile, examined with the micro- scope, presents only a certain amount of mucus, the charac- ters of which we have already described. There are no formed anatomical elements characteristic of this fluid. The fatty and coloring matters are in solution, and not in the form of globules or granules. Composition of the Bile. It is a remarkable fact, that although the bile, in a per- fectly fresh and normal condition, may be obtained from the inferior animals with the greatest facility, no satisfactory analyses of its characteristic principles were made before the examinations of ox-gall by Strecker, in 1848. The bile is, however, one of the most important, but least understood, of the animal fluids ; and our scanty information with regard to its functions has been in a measure due to the want of an exact knowledge of its physiological chemistry. We shall study the composition of the bile very closely, and shall show that it contains two classes of constituents ; one class — ele- ments of secretion — which is reabsorbed ; and another — an element of excretion — which is discharged in a modified form in the faeces. The latter involves a newly-described function of the liver, but our information is much more positive and definite concerning it than with regard to the digestive action of the bile. In treating of the subject of digestion, we have already indicated some of the difficulties, which have been but imperfectly overcome, in the study of the action of the bile as a true secretion, or a recrementitious fluid. The rea- son why the same obscurity has prevailed, until very recently, with regard to the function of the bile as an excretion is that physiologists have regarded what are known as the biliary salts as the only really important constituents ; and these salts have eluded chemical investigation after the dis- charge of the bile into the small intestine. Our recent posi- COMPOSITION OF THE BILE. 261 tive knowledge of the excrementitious function of the liver is due to the recognition of cholesterine, an invariable con- stituent of the bile, as one of the most important of the elements of excretion. Composition of Human Water .......................................... 915'00 to 819'00 Taurocholate, or choleate of soda (NaO,C6aH46XOi4S2) 56-50 " 106-00 Glycocholate, or cholate of soda (XaOjCsa^aNOn) ____ traces. Cholesterine (C25H230) ............................ 1'60 to 2-66 Biliverdine ...................................... 14'00 " 30*00 {. 8.2Q „ 31.QO Margarine, oleine, and traces of soaps . )' ' Choline (C10H13X02) .............................. traces. Chloride of sodium ............................... 2'77 to 3*50 Phosphate of soda ............................... 1-60 " 2'50 Phosphate of potassa ............................. 0'75 " 1'50 Phosphate of lime ............................ ____ 0'50 " 1'35 Phosphate of magnesia. ........................... 0"45 " 0*80 Salts of iron. .................................... 0'15 " 0*30 Salts of manganese ............................... traces " 0"12 Silicic acid ...................................... 0'03 " 0'06 Mucosine ....................................... traces. Loss.. 3-45 to 1-21 1,000-00 1,000-00 There are no peculiarities in the composition of the bile, as regards its inorganic constituents, which demand more than a passing mention. It contains no coagulable organic principle, except mucosine, and all of its constitu- ents are simply solids in solution. The quantity of solid matter is very large, and the proportion of water relatively small ; but in comparing its proportion of water with that of other fluids in the body, as the blood-plasma, lymph and chyle, milk, etc., it must be remembered, as is suggested by 1 This table of the composition of the bile is compiled from Robin (Lemons sur les humeiirs, Paris, 1867, p. 542). In making up the table, the difference be- tween the sum of the constituents and 1,000 has been put in as " loss." We have omitted leucine, tyrosine, and urea, as their existence as proximate prin- ciples of normal bile is doubtful. 262 EXCRETION. Robin,1 that all of these contain water entering into the composition of their coagulable principles ; so that their pro- portion of water, as it is ordinarily given, is really not greater than in the bile. Among the inorganic salts, we find chloride of sodium in considerable quantity, and a large proportion of phosphates. "We also note the presence of salts of iron, of manganese, and a small proportion of silicic acid.2 The fatty and saponaceous matters demand hardly any more extended consideration. A small quantity of margarine and oleine are held in solution, partly by the small propor- tion of soaps, but chiefly by the taurocholate of soda. These principles sometimes exist in larger quantity, and may be discovered in the form of globules. The proportion of soaps is very small. Lecithene, a phosphorized fat, is mentioned by Robin and others, but its constitution is not definitely set- tled. All that is known of this principle is that it is a neutral fatty substance extracted from the bile, and is capa- ble of being decomposed into phosphoric acid and glycerine. Choline (C10H13NO2) is a peculiar alkaloid found in the bile in exceedingly minute quantity. Biliary Salts. The principles which we have called biliary salts are compounds of soda with peculiar organic acids, found no- where but in the liver, and undoubtedly produced in this organ from materials furnished by the blood. The fact that the bile possesses peculiar principles has long been recog- nized. It is unnecessary, however, to follow out in detail the earlier chemical investigations into their properties ; for the biliary matter of Berzelius and the picromel and biliary resin of Thenard are now known to be composed of sev- eral distinct proximate principles. Our exact knowledge 1 ROBIN, Legons sur les humeurs, Paris, 1867, p. 543. 2 The presence of hydrochlorate of ammonia and the ammonio-magnesian phosphate has lately been indicated in the bile by M. Bergeret (de Saint-Leger). — Journal de Vanatomie, Paris, 1869, tome vi., p. 437. BILIARY SALTS. 263 of these substances dates from the analysis of ox-bile by Strecker. He obtained two peculiar acids, cholic and choleic acid, which he found in the bile, in combination with soda.1 In the subsequent researches of Lehmann, these acids are called, respectively, glycocholic and taurocholic acid, and the salts, glycocholate and taurocholate of soda.2 In human bile, the proportion of glycocholate of soda is very small, the biliary matter existing almost entirely in the form of the taurocholate. The taurocholate may be precipi- tated from an alcoholic extract of bile by ether, in the form of dark, resinous drops. These do not crystallize, and the amount of glycocholate, which is precipitated in the same way and soon assumes a crystalline form, is very slight. Prof. Dalton, who has studied the biliary salts very closely, at first was unable to obtain any crystalline matter from human bile, but he has lately found it in minute quantity.3 Taurocholate of Soda (NaO,CMH4iNO14S,).— There is some doubt whether the resinous drops obtained by the ad- dition of an excess of ether to a strong alcoholic extract of bile consist of a proximate principle in a perfectly pure state. These drops are not crystallizable, and this has led to the opinion, expressed by Robin and Yerdeil, that they are impure.4 In fact, even now, there is a certain amount of obscurity with regard to the character of these peculiar biliary salts. In ox-bile, the non-crystallizable and the crystallizable salts exist together; but in human bile, the 1 STRECKER, Untersuchung der Ochsgalle. — Annalen der Chemie und Pharmacie, Heidelberg, 1848, Bd. Ixv., S. 1, et seq. ; Beobacktungen iiber die Gratte ver- schiedener Thiere, Idem, 1849, Bd. Ixx., S. 149, et seq. An analysis of these ob- servations is given in the Journal de pharmacie et de chimie, Paris, 1848, tome xiii., p. 215 ; 1849, tome xv., p. 153 ; and tome xvi., p. 450. 2 LEHMANN, Physiological Chemistry, Philadelphia, 1855, vol. ii., p. 201, ct seq. 3 DALTON, Treatise on Human Physiology, Philadelphia, 1867, p. 167. 4 ROBIN ET YERDEIL, Traite de chimie anatomique, Paris, 1853, tome ii., p. 473. 264 EXCBETION. greatest part is in the 'form of what we know as the tauro- cholate of soda. These salts may be readily obtained from ox-bile and separated from each other by the following process : The bile is first evaporated to dryness and pulverized. The dry residue is then extracted with absolute alcohol and filtered. In this part of the process, Dr. Dalton uses five grains of the dry residue to one fluidrachm of alcohol.1 The filtered fluid is of a clear, yellowish color, and contains fats and coloring matter, in addition to the biliary salts. To precipitate the biliary salts, a small quantity of ether is added, which pro- duces a dense, white precipitate that redissolves by agitation. Another small quantity of ether is again added, and the precipitate thus produced is dissolved by shaking the mix- ture. This process is repeated carefully, adding the ether and shaking the mixture after each step, until the precipi- tate becomes permanent. An excess of ether — from eight to ten times the bulk of the alcoholic extract used — is then added, the test-tube or flask is carefully corked, and the mixture is set aside to crystallize. Gradually the dense, white precipitate falls to the bottom of the vessel or becomes attached in the form of resinous drops to the sides of the glass ; and in from six to twenty-four hours it begins to form delicate acicular crystals, arranged in rosettes. These are crystals of the glycocholate of soda; and the non-crystal- lizable matter remaining is the taurocholate of soda. To separate these two salts, the ether is rapidly poured off, and the crystalline and resinous residue is dissolved in distilled water. On the addition to this solution of a little acetate of lead, the glycocholate is decomposed and precipi- tated in the form of glycocholate of lead, leaving the tauro- 1 DALTON, Treatise on Human Physiology, Philadelphia, 1867, p. 162, ct seq., and On the Constitution and Physiology of the Bile. — American Journal of the Medical Sciences, Philadelphia, 1857, New Series, vol. xxxiv., p. 305, et seq. The details of the processes for the extraction of the biliary salts are taken from Dalton, who has studied this subject very carefully, and whose method is simple and entirely satisfactory. BILIAKY SALTS. 265 cholate in solution. The glycocholate of lead is then sepa- rated by filtration, and the subacetate of lead is added to the filtered fluid. This decomposes the taurocholate, and the taurocholate of lead is precipitated. The subacetate of lead will decompose both the glycocholate and the taurocholate, but the glycocholate only is acted upon by the acetate of lead. The glycocholate and the taurocholate of lead are then carefully washed and treated separately with the car- bonate of soda, which gives the original salts in nearly a pure state. The taurocholate of soda is a proximate principle of the bile, and it is not necessary to describe fully in detail the purely chemical processes by which it is decomposed. With a little care, the taurocholic acid may be obtained in a state of tolerable purity, and by prolonged boiling with pot- ash, may be decomposed into a new acid and taurine. Some confusion exists in the books about the name of this new acid. Strecker calls it cholalic acid, and applies the name of cholic acid to what we have described as glycocholic acid. As we have adopted the nomenclature of Lehmann, we will call it cholic acid. Its formula is C48H89O9HO. The for- mula for taurine is C4H7NO8S2. It must be remembered, however, that these substances are formed artificially and are not true proximate principles. They have been described in explanation of the name taurocholic acid, which has been applied to it on the assumption that the different biliary acids are formed of cholic acid united with taurine or other basic substances. If human bile be treated in the manner just described, frequently no crystalline matter is obtained, and when it exists, it is in very small quantity. The great mass of the precipitate is composed of the taurocholate of soda. This, when it has been thoroughly purified, is whitish and gummy, very soluble in water and alcohol, and insoluble in ether. It is melted with slight heat, and is inflammable. Its reac- tion is neutral. It has a peculiar, sweetish-bitter taste. The 266 EXCRETION. proportion of this principle in the bile is always very large, though subject to considerable variation. It has very little in common with the salts of fatty origin, either in its general properties or composition, inasmuch as it is entirely insolu- ble in ether, and its acid contains nitrogen. Another pecu- liarity in its composition, and one which serves to distinguish it from the glycocholate of soda, is that it contains two atoms of sulphur. One of its important properties in the bile is that it aids in the solution of the fats contained in this fluid, and to a certain extent, probably, in the solution of cholesterine. Glycocholate of Soda (NaO,0MH4rN"On).— We have ne- cessarily described the process for the extraction of the glycocholate of soda, in connection with the taurocholate. The glycocholate is crystallizable and is more easily obtained in a condition of purity. The chief chemical points of dif- ference between these salts are, that the glycocholate is pre- cipitated by the acetate of lead as well as the subacetate, the acetate having no effect upon the taurocholate of soda, and that the glycocholic acid does not contain sulphur. By treating glycocholic acid with potash at a high temperature, it is decomposed into cholic acid and glycine, or glycocoll (C4H5]^04). It is this which has given it the name of glyco- cholic acid. In their physiological relations, the two biliary salts are, as far as we know, identical. Origin of the Biliary Salts. — There can be no doubt that these principles are elements of secretion, and are pro- duced de novo in the substance of the liver. In no instance have they ever been discovered in the blood in health ; and, although they present certain points of resemblance with some of the constituents of the urine, they have never been found in the excreta. In experiments made by Miiller,1 1 MUELLER, Manual de physiologic, Paris, 1851, tome L, p. 122. CHQLESTEKESTE. 267 Kunde,1 Lehmann,3 and Moleschott,3 on frogs, in which the liver was removed and the animal survived several days, and in the observations of Moleschott, between two and three weeks, it was found impossible to determine the accumula- tion of the biliary salts in the blood. There is no reason, therefore, for supposing that these principles are products of disassimilation. Once discharged into the intestine, they undergo certain changes, and can no longer be recognized by the usual tests ; but experiments have shown that, changed or unchanged, they are absorbed with the elements of food.4 They are probably the elements concerned in the digestive function of the bile. Cholesterine^ C26H22O. Before the publication, in 1862, of a memoir on a new excretory function of the liver, the function and relations of cholesterine were not known, and this substance was hardly mentioned in most works on physiology. As we believe that it must now be recognized as one of the most impor- tant of the products of disassimilation, it becomes interesting and important to study its properties more closely. The first description we have of cholesterine is by Fourcroy, who states that it was discovered by Poulletier de la Salle, in 1Y82.5 Fourcroy also described adipocire, which he likened to cholesterine, although he did not con- 1 KUNDE, De Hepatis Extirpatione, Dissertatio Inauguralis, Berolini, 1850. 2 LEHMANN, Physiological Chemistry, Philadelphia, 1855, vol. L, p. 476. s MOLESCHOTT, Sur la secretion du sucre et de la bile dans le foie. — Comptes rendus, Paris, 1855, tome xl., p. 1040. Moleschott was more successful, in these experiments, than any of those who had preceded him. He extirpated the liver from a great number of frogs, and succeeded in keeping them alive for two or three weeks ; but he could never detect in the blood the bile-pigment or the biliary salts. 4 See vol. ii., Digestion, p. 374, et seq. 5 FOURCROY, Memoire sur la nature des alterations qtfeprouvent quelques hu- meurs animates, par Veffet des maladies etpar Vaction des remedes. — Memoires de la Societe Royale de Medecine, 1782-1783, Paris, 1788, p. 489. The substance 268 EXCRETION. sider the two substances identical.1 In 1814, Chevreul gave a full description of cholesterine, and extracted it from the bile of the human subject and some of the inferior ani- mals.3 It was afterward found by different observers, in gall-stones, intestinal concretions, cysts, and tumors. In 1830, Denis described a substance in the blood, which he thought was cholesterine, and its discovery in this fluid is attributed to him by most authors ; but in 1838, he acknowl- edged the error of his first observation,8 and admits that cholesterine, with a new substance analogous to it, called seroline, was discovered in the blood, in 1833, by Boudet.4 Cholesterine is now recognized as a normal constituent of various of the tissues and fluids of the body. Most authors state that it is found in the bile, blood, liver, nervous tissue, crystalline lens, meconium, and faecal matter. "We have found it in all these situations, with the exception of the faeces,6 where it does not exist normally, having been transformed into stercorine in its passage down the intestinal canal.8 In the fluids of the body, cholesterine exists in solution ; but by virtue of what constituents it is held in this condition, described by Fourcroy was undoubtedly cholesterine; but it remained for Chevreul to describe its properties accurately and give it the name by which it is now known. The observations of Chevreul will be referred to further on. 1 FOURCROY, Deuxieme memoir e sur les matieres animates trouvees dans la Ci- metiere des Innocens d Paris. — Annales de chimie, Paris 1791, tome viii., p. 62, et seq. 2 CHEVREUL, Reclierches chimiques sur plusieurs corps gras, Cinquieme me- moire. Des corps qu'on a appelle adipocire. — Annales de chimie, Paris, 1815, toine xcvi., p. 7. 3 DENIS, Essai sur ^application de la chimie d V etude physiologique du sang de rhomme, Paris, 1838, p. 147. 4 BOUDET, Nouvelles rechercJies sur la composition du serum du sang humain. — Annales de chimie et de physique, Paris, 1833, tome lii., p. 337. 5 For a table of the quantities of cholesterine in various situations, see an article by the author, on a New Excretory Function of the Liver. — American Jour- nal of the Medical Sciences, Philadelphia, 1862, New Series, vol. xliv., p. 313. 6 See vol. ii., Digestion, p. 399, et seq. CHOLE8TEBINE. 269 is not entirely settled. It is stated that the biliary salts have the power of holding it in solution in the bile, and that the small amount of fatty acids contained in the blood hold it in solution in that fluid ; but direct experiments on this point are wanting. In the nervous substance and in the crystalline lens, it is united " molecule d molecule " to the other elements which go to make up these tissues. After it is discharged into the intestinal canal, when it is not changed into sterco- rine, it is to be found in a crystalline form ; as in the meco- nium, and in the faeces of animals in a state of hibernation. In pathological fluids and in tumors, it is found in a crystal- line form, and may be detected by microscopic examination. Cholesterine is usually described as a non-nitrogenized principle, having all the properties of the fats, except that of saponification with the alkalies. Its chemical formula is given as C26HMO. It is neutral, inodorous, crystallizable, insoluble in water, soluble in ether, very soluble in hot alco- hol, though sparingly soluble in cold. It is inflammable, and burns with a bright flame. It is not attacked by the alkalies, even after prolonged boiling. When treated with strong sulphuric acid, it strikes a peculiar red color, which is mentioned by some as characteristic of cholesterine. We have found that it possesses this character in common with the so-called seroline.1 Cholesterine may easily and certainly be recognized by the form of its crystals, the characters of which can be made out by means of the microscope. They are rectangular or rhomboidal, exceedingly thin and transparent, of variable size, with distinct and generally regular borders, and fre- quently arranged in layers, with the borders of the lower strata showing through those which are superimposed. This arrangement of the crystals takes place when cholesterine is present in considerable quantity. In pathological speci- 1 This similarity in the reactions of cholesterine and seroline with sulphu- ric acid is mentioned by Berard (Cours de physiologie, Paris, 1851, tome iii., p. 117). 270 EXCRETION. mens, the crystals are generally few in number and isolated. The plates of cholesterine are frequently marked by a cleav- age at one corner, the lines running parallel to the borders ; and frequently they are broken, and the line of fracture is generally undulating. Lehmann attaches a great deal of importance to measurements of the angles of the rhomboid. According to this author, the obtuse angles are 100° 30', and the acute 79° 30V "We have examined a great number of specimens of cholesterine, extracted from the blood, bile, brain, liver, and occurring in tumors, and have not observed that the crystals have definite angles. Frequently the plates are rectangular, and sometimes almost lozenge-shaped. It is by the transparency of the plates, the parallelism of their borders, and their tendency to break in parallel lines, that we recognize cholesterine. Lehmann seems to consider the tablets of this substance as regular crystals having in- variable angles. From examination during crystallization, it seems more probable that they are not crystals, but frag- ments of micaceous sheets, which, from their extreme tenuity, are easily broken. In examining a specimen from the me- conium, which was simply extracted with hot alcohol, it was easy to observe a transparent film forming on the surface of the alcohol soon after it cooled, and this, on microscopic examination, in situ, disturbing the fluid as little as possible, was found to be marked by long parallel lines. When the fluid had partially evaporated, the crust became broken and the fragments took the form of the ordinary crystals of cho- lesterine, but they were larger and more regular. The tab- lets were exceedingly thin, and regularly divided into deli- cate plates, with the characteristic corner-cleavages of the cholesterine ; and as the focus of the instrument was changed, new layers were brought into view. Crystals of cholesterine melt at 293° Fahr., but are formed again when the temperature falls below that point. Accord- ing to Lehmann, they may be distilled in vacuo at 680°, 1 LEHMANN, Physiological Chemistry, Philadelphia, 1855, vol. i., p. 244. CHOLESTERES'E. 271 without decomposition. The determination of the fusing point is one of the means of distinguishing it from seroline,1 which fuses at 90° 8'. Without considering in detail the processes which have been employed by other observers for the extraction of cho- lesterine from the blood, bile, and various tissues of the body, we will simply describe the method which has been found most convenient in the various analyses we have made for this substance. In analyses of gall-stones, the process is very simple ; all that is necessary being to pulverize the mass, extract it with boiling alcohol, and filter the solution while hot, the cholesterine being deposited on cooling. If the crys- tals be colored, they may be redissolved, and filtered through animal charcoal. This is the process employed by Poulletier de la Salle, Fourcroy, and Chevreul. It is only when this substance is mixed with fatty matters, that its isolation is a matter of any difficulty. In extracting cholesterine from the blood, we have operated on both the serum and clot, and in this way have been able to demonstrate it in greater quan- tities in this fluid than have been observed by others, who have employed only the serum. The following is the pro- cess for quantitative analysis, which was determined upon after a number of experiments : The blood, bile, or brain, as the case may be, is first care- fully weighed, then evaporated to dryness over a water-bath, and pulverized in an agate mortar. The powder is then treated with ether, in the proportion of about a fluidounce for every hundred grains of the original weight, for from twelve to twenty-four hours, agitating the mixture occasion- ally. The ether is then separated by filtration, throwing a little fresh ether on the filter so as to wash through every trace of the fat, and the solution set aside to evaporate. If the fluid, especially the blood, have been carefully dried and pulverized, when the ether is added, it divides it into a very fine powder and penetrates every part. After the ether has 1 LEHMANN, loc. cit. 272 EXCRETION. evaporated, the residue is extracted with boiling alcohol, in the proportion of about a fluidrachm for every hundred grains of the original weight of the specimen, filtered while hot into a watch-glass, and allowed to evaporate spontane- ously. To keep the fluid hot while filtering, the whole appa- ratus may be placed in the chamber of a large water-bath, or, as the filtration is generally rapid, the funnel may be warmed by plunging it into hot water, or steaming it, taking care that it be carefully wiped. We now have the choleste- rine mixed with a certain quantity of saponifiable fat. After the fluid has evaporated, we can see the cholesterine crystal- lized in the watch-glass, mingled with masses of fat. This we remove by saponification with an alkali ; and for 'this purpose, we add a moderately strong solution of caustic pot- ash, which we allow to remain in contact with the residue for from one to two hours. If much fat be present, it is best to heat the mixture to a temperature a little below the boil- ing point ; but in analyses of the blood this is not necessary. The mixture is then to be largely diluted with distilled water, thrown upon a small filter, and thoroughly washed till the fluid which passes through is neutral. "We then dry the filter, and fill it up with ether, which, in passing through, dissolves out the cholesterine. The ether is then evaporated, the residue extracted with boiling alcohol, as before, the alcohol collected on a watch-glass previously weighed, and allowed to evaporate. The residue consists of pure choleste- rine, the quantity of which may be estimated by weight. The accuracy of this process may be tested by means of the microscope ; for the crystals have so distinctive a form, that it is easy to determine, by examining the watch-glass, whether the cholesterine be perfectly pure. In making this analysis quantitatively, it is necessary to be very careful in all the manipulations ; and for determining the weight of such minute quantities, an accurate and delicate balance, one, at least, that will turn with the thousandth of a gramme, carefully adjusted, must be employed. With these precau- BILIVEKDINE. 273 tions, the quantity of cholesterine in any fluid or solid may be determined with perfect accuracy ; and the estimate may be made in so small a quantity as from fifteen to twenty grains of blood. In analyzing the brain and bile, we found it necessary to pass the first ethereal solution through animal charcoal, to get rid of the coloring matter. In doing this, the charcoal must be washed with fresh ether till the solu- tion which passes through is brought up to the original quantity. The other manipulations are the same as in ex- aminations of the blood. In examining the meconium, we found that the cholesterine which crystallized from the first alcoholic extract was so pure that it was not necessary to subject it to the action of an alkali. The proportion of cholesterine in the bile is not very large. In the table, it is estimated at^from 1*60 to 2*66 parts per thousand. In a single examination of the hu- man bile, we found the proportion 0'618 of a part per thousand. The origin and destination of this principle involve, as we believe, an office of the liver which has not hitherto been recognized by physiologists ; and we will consider these ques- tions specially, under the head of the excretory function of the liver. Biliverdine. The coloring matter of the bile bears a certain resem- blance to the coloring matter of the blood, and is supposed to be formed from it in the liver. It gives to the bile its peculiar tint, and has, as we have remarked, the property of coloring the tissues with which it comes in contact. When- ever the flow of bile is seriously obstructed, the coloring matter is absorbed by the blood, and can be readily detected in the serum, in the urine, and in the color of the skin and conjunctiva. In the bile it is liquid, but it may be coagu- lated and extracted by various processes. It does not exist naturally in the form of pigmentary granulations. 18 274 EXCRETION. This principle is precipitated from the bile by boiling with milk of lime. The filtered residue is then decomposed with hydrochloric acid, which unites with the lime and leaves a fatty residue of an intense green color. The fat is then removed by repeated washings with ether (a very long and difficult process). The precipitate is then redissolved in alcohol with ether added, which gives to the liquid a bluish-green color, and leaves, after evaporation, a dark- green powder. This powder contains iron, but its pro- portion has never been accurately estimated. The mat- ter thus obtained is insoluble in water and in chloroform, but is soluble in ether, alcohol, sulphuric and hydrochloric acid.1 It is unnecessary to follow out in detail all of the chemi- cal investigations which have been made into the ultimate composition and the modifications of this and the other col- oring matters. According to Robin,8 the empirical formula for biliverdine, deduced from the analyses of Scherer, is C24H16NO4 . No account is taken in these analyses of the iron, the existence of which cannot be doubted. Upon the addition of nitric acid, or better, of nitric mixed with nitrous acid, biliverdine is acted upon in a peculiar way, producing a play of colors, which is recognized as one of the tests for bile. Tests for Bile. It is frequently desired, particularly in pathological in- vestigations, to ascertain, by some easy test, the fact of the presence or absence of bile in various of the fluids and solids of the body. It is, indeed, a most interesting physiological question to determine the course and destination of the biliary salts after the bile has passed into the intestinal canal ; and this can be done only by the application of ap- propriate tests to the contents of the alimentary tract and 1 ROBIN ET VERDEIL, Traite de chimie anatomique, Paris, 1853, tomeiii., p. 389. '.ROBIN, jtepong.sw les humeurs, Paris, 1867, p. 550. TESTS FOB BILE. 275 the blood of the portal system. The ingredients of the bile which it is important to detect are biliverdine, the biliary salts, and cholesterine. The last-named substance can be detected best by applying the method which we have just described for its extraction ; but several tests have been pro- posed for the detection, on the one hand, of the coloring matter of the bile, and on the other, of the peculiar, biliary salts. Test for Biliverdine. — There is one test so simple and easy of application, that it alone will suffice for the prompt detection of biliverdine. This is peculiarly applicable to the urine, where the presence or absence of bile frequently becomes an important question. We are led generally to suspect the presence of bile in the fluids of the body by the peculiar color. If we spread out the suspected fluid in a thin stratum upon a white sur- face, as a porcelain plate, and add a single drop of nitric acid, or, what is better, nitroso-nitric acid, if the coloring matter of bile be present, a peculiar play of colors will be observed at the circumference of the drop of acid as it diffuses itself. The color will rapidly change from blue to red, orange, purple, and finally yellow. This is due to the action of the acid upon the biliverdine ; and this test will not indicate the presence of either cholesterme or the biliary salts. It is used, therefore, only when we wish to determine the presence of the coloring matter of the bile. Test for the Biliary Salts. — The best, and, indeed, the only reliable test for the biliary salts, was proposed many years ago by Pettenkofer,1 and is now generally known as Pettenkofer's test. This requires some care and practice in its application, but it is entirely reliable ; and although it has been objected that there are other substances than the 1 PETTENKOFER, Notiz uber eine neue Reaction auf Galle und Zucker.—An- nalen der Chemie und Pharmacie, Heidelberg, 1844, Bd. Hi., S. 90. 276 EXCRETION. biliary salts which produce similar reactions, these are not met with in the animal fluids, and consequently are not liable to produce confusion. If a considerable quantity of bile be present in any fluid, and if there be not a large ad- mixture of animal matters, the test may be employed with- out any preparation ; but in delicate examinations, it is best to evaporate the suspected liquid, extract the residue with absolute alcohol, precipitate with ether, and dissolve the ether-precipitate in distilled water. By this means a clear solution is obtained, which will react distinctly, even when the biliary salts exist in very small quantity. Petten- kofer's test is applicable to any of the biliary salts, whatever 6e their form, and the reaction is dependent upon the pres- ence of cholic acid, which enters into the composition of all the varieties of the biliary acids. The following is one of the most common methods of employing Pettenkofer's test : To the suspected solution we add a few drops of a strong solution of cane-sugar in water. Sulphuric acid is then slowly added, to the extent of about two-thirds of the bulk of the liquid. It is recommended to add the acid slowly, so that the temperature shall be but little raised. If a large quantity of the biliary salts be present, a red color shows itself almost immediately at the bottom of the test-tube, and soon extends through the en- tire liquid, rapidly deepening until it becomes of a dark lake or purple. If the biliary matters exist in very small pro- portion, it may be several minutes before any red color makes its appearance, and the change to a purple is corre- spondingly slow, the whole process occupying from fifteen to twenty minutes. Many organic matters may be rendered dark by the action of the acid, and the sugar itself will be acted upon, even if no bile be present, but the color due to the sugar alone is yellow. The peculiar play of colors above described can easily be recognized after a little practice, and is observed only in the presence of the biliary salts. The ordinary modifications in the application of this test EXCRETORY FUNCTION OF THE LIVER. 277 are unimportant. Some recommend to add the sulphuric acid first, and then to add the solution of sugar ; and some, after adding to the liquid two-thirds of its volume of sul- phuric acid, drop into the mixture one or two lumps of cane- sugar. The reaction with the biliary salts is essentially the same, whichever of these methods be employed. Excretory Function of the Liver. In 1862, in studying the properties and physiological re- lations of cholesterine, we gave the first definite account of an excretory function of the liver. The experiments and observations upon which we based our conclusions were extended and laborious, and, as far as we know, have not been repeated in detail by other observers ; but the results must be taken as positive, if the accuracy of the experiments be admitted, and they have been adopted, to a greater or less extent, by scientific authorities. The details of these ex- periments are too elaborate to be given in full, as contained in the original memoir.1 The few statements with regard to the function of choles- terine to be found in works published before 1862 are very indefinite. In most works on physiology, this substance is hardly mentioned, it being generally regarded as a curious principle, interesting only to the physiological chemist. We have given, in the memoir referred to, extracts from the works of Carpenter, Lehmann, Mialhe, and Dalton, which contain all that is said of the probable function of choles- terine ; and these quotations, which embody about all that we could find on the subject, show that its office was not in the least understood. Inasmuch as cholesterine is the only excrernentitious principle as yet discovered in the bile, bear- ing the same relation to this fluid that urea does to the urine, 1 FLINT, Jr., Experimental Researclies into a New Excretory Function of the Liver. — American Journal of the Medical Sciences, Philadelphia, 1862, New Se- ries, vol. xliv., p. 305, et seq. ; and RechercJies experimentales sur une nouveUe fonction du foie, Paris, 1868. 278 EXCRETION. it is evident that the ideas of physiologists, with regard to any excretory function of the liver, must have been very indefinite before the relations of cholesterine had been de- termined. The first question which arises is whether the liver has any excretory function. Some authors, notably Blondlot, have assumed that the bile is purely excrement! tious and has no function as a secretion. This question we have fully discussed in another place.1 The confusion that has arisen with regard to this point has been due to the fact that those who adopted the view that the bile was simply an excretion denied to it any digestive properties ; while, on the other hand, those who believed it to be concerned in digestion would not admit that it was an excretion. "We have shown conclusively, in treating of intestinal digestion, that the bile is so important in this process, as to be essential to life ; but we have shown, at the same time, that the liver eliminates from the blood one of the most important of the products of disassimilation. It will be found important, as bearing upon the probable function of the bile, to apply to this fluid the general considerations contained in the first chapter, on the distinctions between secretions and excretions. Cells of glandular epithelium are constantly manufac- turing, out of materials furnished by the blood, the elements of the true secretions ; but these elements do not preexist in the blood, they appear de novo in the secreting organ, and never accumulate in the system when the function of the secreting organ is disturbed. Again, the true secretions are not discharged from the body, but have a function to perform in the economy, and are poured out by the glands intermit- tently, at the times when this function is called into action. As far as the biliary salts (the taurocholate and glycocholate of soda) are concerned, the bile corresponds entirely to the true secretions. These principles are manufactured by the liver, they do not preexist in the blood, and they do not ac- 1 See vol. ii., Digestion, p. 362, et seq. EXCRETORY FUNCTION OF THE LIVER. 279 cumulate in the blood when their formation in the liver is disturbed. The researches of Bidder and Schmidt and others have shown that although we cannot detect the biliary salts in the blood or chyle coming from the intestine, these princi- ples are not discharged in the faeces.1 All of these facts point to an important function of the bile as a secretion. It is true that it is discharged constantly, but during digestion its flow is very much more abundant than at any other time. It is pretty well established that during the intervals of the flow of the secretions, the glands are manufacturing the materials of secretion, which are washed out, as it were, in the great afflux of blood which takes place during what has been called the functional activity of the gland. Now if the liver, in addition to its function as a secreting organ, be constantly forming bile for the purpose of eliminating an excremen- titious matter, it is to be expected that the bile would always contain a certain proportion of its elements of secretion. The constant and invariable presence of cholesterine in the bile assimilates it in every regard to the excretions, of which the urine may be taken as the type. Cholesterine always exists in the blood and in certain of the tissues of the body. It is not produced in the substance of the liver, but is merely separated from the blood by this organ. It is constantly passed into the intestine, and is discharged, although in a modified form, in the faeces. We know of no function which it has to perform in the economy, any more than urea, or any other of the excrementitious principles of the urine ; and we have shown, in the memoir already referred to, that it accumulates in the blood in certain cases of organic disease of the liver and gives rise to certain symp- toms of blood-poisoning. Origin of Cholesterine. — Cholesterine exists in largest quantity in the substance of the brain and nerves. It is also found in the substance of the liver — probably in the 1 See vol. ii., Digestion, p. 374. 280 EXCRETION. bile contained in this organ — the crystalline lens, and the spleen ; l but with these exceptions, it is found only in the nervous system and blood. Two views present themselves with regard to its origin. It is either deposited in the- ner- vous matter from the blood, or is formed in the brain and taken up by the blood. This is a question, however, which can be settled experimentally, by analyzing the blood for cholesterine as it goes to to the brain by the carotid, and as it comes from the brain by the internal jugular. The cho- lesterine being found also in the nerves, and, of course, a large quantity of nervous matter existing in the extremities, it is desirable at, the same time to make an analysis of the venous blood from the general system. With a view of determining this question, we made the following experiments : Experiment I. — In this experiment, specimens of blood were taken from the carotid, the internal jugular, the vena cava, hepatic veins, hepatic artery, and portal vein, in a liv- ing animal (a dog about six months old). In addition, we took a specimen of bile from the gall-bladder, and some of the substance of the brain. These were all carefully ex- amined for cholesterine, and the following were the main results : In the brain cholesterine was found in large quan- tity. There was no cholesterine in the extract of the blood from the carotid, examined three days after, and but a few crystals, eleven days after. Cholesterine was almost imme- diately discovered in the extract of the blood from the in- ternal jugular, and the crystals were present in large num- bers on the twelfth day. In this experiment the animal was etherized when the blood was taken, and the examinations 1 In 1854, Marcet described a substance extracted from the spleen, which he thought was analogous to cholesterine (An account of the Organic Chemical Constituents, or Immediate Principles of the Excrements of Man and Animals in the Healthy State. — Philosophical Transactions, London, 1854, p. 269); and in 1857, he fully recognized its existence in this organ (On the Immediate Prin- ciples of the Excrements of Man and Animals in the Healthy State. — Philosophical Transactions, London, 1857, p. 412). EXCRETORY FUNCTION OF THE LIVER. 281 for cholesterine were not quantitative. In the succeeding experiments, the proportion of cholesterine in the different specimens of blood was accurately estimated, and, in most of them, no anaesthetic was used during the operative pro- cedure. Experiment II. — A medium-sized adult dog was put un- der the influence of ether, and the carotid artery, internal jugular, and femoral vein exposed. Specimens of blood were drawn, first from the internal jugular, next from the carotid, and last from the femoral vein. These specimens were received into carefully -weighed vessels, and weighed. They were then analyzed for cholesterine by the process already described, and the following results obtained : Quantity of Blood. Cholesterine. Cholesterine per grains. grains. 1,000 pte. Carotid 179-462 0'139 0'774 Internal jugular 134'780 O'lOS O'SOl Femoral vein 133-886 0-108 0'806 Percentage of increase in the blood from the jugular over the arterial blood 3-488 Percentage of increase in the blood from the femoral vein 4'134 This experiment shows an increase in the quantity of cholesterine in the blood in its passage through the brain, and an increase, even a little greater, in the blood passing through the vessels of the posterior extremity. To facilitate the operation, however, the animal was brought completely under the influence of ether, which, from its action on the brain, would not improbably produce some temporary dis- turbance in the nutrition of that organ, and consequently interfere with the experiment. For the purpose of avoiding this difficulty, we performed the following experiments with- out administering an anaesthetic : Experiment III. — A small young dog was secured to the operating-table, and the internal jugular and carotid ex- posed on the right side. Blood was taken, first from the jugular, and afterward from the carotid. The femoral vein 282 EXCBETION. on the same side was then exposed, and a specimen of blood was taken from that vessel. The animal was very quiet under the operation, though no anaesthetic was used, so that the blood was drawn without any difficulty and without the slightest admixture. The three specimens were analyzed for cholesterine, with the following results : Quantity of Blood. Cholesterine. Cholesterine per grains. grains. 1,000 pts. Carotid 143-625 0-679 0-967 Internal jugular 29'956 0'046 1-545 Femoral vein 45'035 0'046 1-028 Percentage of increase in the blood from the jugular over the arterial blood 59-772 Percentage of increase in the blood from the femoral vein 6*308 Experiment IY. — A large and powerful dog was secured to the operating-table, and the carotid and internal jugular exposed. Specimens of blood were taken from these vessels, first from the jugular, and were carefully weighed and ana- lyzed for cholesterine in the usual way. The following re- sults were obtained : Blood. Cholesterine. Cholesterine per grains. grains. 1,000 pts. Carotid 140*847 0-108 0*768 Internal jugular 97*811 0'092 0'947 Percentage of increase in the blood passing through the brain 23*307 Experiment III. shows a very considerable increase in the quantity of cholesterine in the blood passing through the brain, while the increase is comparatively slight in the blood of the femoral vein. The proportion of cholesterine is also large in the arterial blood, compared with other observations. Experiment IY. shows but a slight difference in the quantity of cholesterine in the arterial blood in the two ani- mals ; the proportion in the animal that was etherized being 0*774: per 1,000, and in the animal that was not etherized 0-768 per 1,000, the difference being but 0'006 ; but, as was suspected, the ether seemed to have an influence on the quan- EXCRETORY FUNCTION OF THE LIVER. tity of cholesterine absorbed by the blood in its passage through the brain. In the first instance the increase was but 3-4:88 per cent., while in the latter it was 23'307 per cent. The natural conclusions to be drawn from these observa- tions, with regard to the origin of cholesterine in the econ- omy, are the following: It has been ascertained that the brain and nerves contain a large quantity of this substance, which is found in hardly any other of the tissues of the body ; and these experiments, especially Experiments III. and IV., show that the blood that comes from the brain contains a much larger quantity of cholesterine than the blood supplied to this organ. The conclusion is, then, that cholesterine is produced in the brain, and is taken up by the blood as it passes through this organ. But the brain is not the only part where cholesterine is produced. It will be seen by Experiment II. that there is 4'134 per cent., and in Experiment III. 6'30S per cent, of increase in the cholesterine in the passage of the blood through the inferior extremities, and probably about the same in other parts of the muscular system. In examining these tissues chemically, we find that the muscles contain no cholesterine, but that it is abundant in the nerves ; and as we have found that the proportion of cholesterine is im- mensely increased in the passage of the blood through the great centre of the nervous system, taken, as the specimens were, from the internal jugular, which collects the blood mainly from the brain and very little from the muscular sys- tem, it is rendered very probable that, in the general venous system, the cholesterine which the blood contains is produced in the substance of the nerves. If this be true, and if cholesterine be one of the prod- ucts of the disassimilation of nervous tissue, its formation would be proportionate in activity to the nutrition of the nerves ; and any thing which interfered to any great extent with their nutrition would diminish the quantity of choleste- 284 EXCRETION. rine produced. In the production of urea by the general system, which is an analogous process, muscular activity in- creases the quantity, and inaction diminishes it, on account of the effect upon nutrition. In cases of paralysis, we have a diminution of the nutritive forces in the parts affected, especially of the nervous system, which, after a time, be- comes so disorganized that although the cause of the paraly- sis be removed, the nerves cannot resume their functions. It is true we have this disorganization taking place to a certain extent in the muscles, but it is by no means as marked as it is in the nerves. We should be able, then, to confirm the observations on animals, by examining the blood in cases of paralysis, when we should expect to find a very marked dif- ference in the quantity of cholesterine, between the venous blood coming from the paralyzed parts, and the blood from other parts of the body. "With this point in view we made analyses of the blood from both arms, in three cases of hemiplegia. Case I. — Sarah Rumsby, set. 47, was affected with hemi- plegia of the left side. Two years ago she was taken with apoplexy, and was insensible for three days. When she re- covered consciousness, she found herself paralyzed on the left side. She said she had epilepsy four or five years before the attack of apoplexy. Now she has entire paralysis of motion on the affected side, with the exception of some slight power over the fingers, but sensation is perfect. The speech is not affected. The general health is good. Case II. — Anna Wilson, set. 23, Irish, was affected with hemiplegia of the right side. Four months ago she was taken with apoplexy, from which she recovered in one day, with loss of motion and sensation on the right side. She is now im- proving and can use the right arm slightly. The leg is not so much improved, because she will make no effort to use it. Case III. — Honora Sullivan, Irish, set. 40, was affected with hemiplegia of the right side. About six months ago she was taken with apoplexy, and recovered consciousness EXCRETORY FUNCTION OF THE LIVER. 285 the next day, with paralysis. The leg was less affected than the arm, from the first. The cause was supposed by Dr. Flint, the attending physician, to be due to an embolus. Her condition is now about the same, as regards the arm, but the leg has somewhat improved. These cases all occurred at the Black well's Island Hos- pital. The treatment in all consisted of good diet, frictions, passive motion, and use of the paralyzed members as much as possible. A small quantity of blood was drawn from both arms in these three cases. It was drawn from the paralyzed side, in each instance, with great difficulty, and but a small quantity could be obtained. The specimens were all examined for cholesterine, with the following results : Table of Quantity of Cholesterine in Blood of Paralyzed and Sound Sides, in three cases of Hemiplegia. Blood. Choles- terine. Cholesterine per 1,003. grains. grains. Case I. Paralyzed side. 55-458 The watch-glass contained 0'031 of a grain of a granular sub- stance, but the most careful examination failed to show a Do. Sound side. 128-407 0-062 single crystal of cholesterine. 0-481. Case II. Paralyzed side. Do. Sound side. 18-381 66-396 0-062 Same as Case I. 0-808. Case III. Paralyzed side. Do. Sound side. 21-842 52-261 0-031 Same as Case I. 0-579. The result of these examinations is very interesting : not a single crystal of cholesterine was found in any of the three specimens of blood from the paralyzed side, while about the normal quantity was found in the blood from the sound side. As the nutrition of other tissues is interfered with in paraly- 286 EXCRETION. sis, it is impossible to say positively, from these observations alone, that the cjiolesterine is produced in the nervous sys- tem only. But the nutrition of the nerves is undoubtedly most affected ; and these observations, taken in connection with the preceding experiments on animals, point very strongly to such a conclusion. Our experiments upon animals were so marked and in- variable in their results, even when performed under differ- ent conditions, that they can leave hardly any doubt of the fact that the blood, in passing through the brain, takes up cholesterine. It is more difficult to show, by actual demon- stration, that the general system of nerves also gives up cholesterine to the blood ; but the fact that the venous blood coming from the extremities contains more cholesterine than the arterial blood, taken in connection with the fact that none of the tissues of the extremities contain cholesterine, except the nerves, renders it more than probable that the nerves, as well as the brain, are the seat of the formation of this principle. The observations upon the cases of paralysis are interest- ing, taken in connection with the experiments on animals. Such observations should, of course, be much more elaborate and extended to lead, of themselves, to positive results ; but they go far to confirm our views with regard to the probable origin of cholesterine in the nervous system. Elimination of Cholesterine by the Liver. — We at- tempted to demonstrate experimentally the separation of cholesterine from the blood by the liver, in the same way that we demonstrated its passage into the blood circulating through the brain. In the first series of experiments on this subject, we endeavored to show, on the same animal, the origin of cholesterine in certain parts, and the mechanism of its elimination. In these experiments, which were only approximative, as we had not then succeeded in extract- ing the cholesterine perfectly pure, we commenced with the EXCRETORY FUNCTION OF THE LIVER. 287 arterial blood, examining it as it went into the brain by the carotid, analyzing the substance of the brain, then analyzing the blood as it came out of the brain by the internal jugular, examining the blood as it went into the liver by the hepatic artery and portal vein, examining the secretion of the liver, then the blood as it came out of the liver by the hepatic vein, examining also the blood of the vena cava in the abdo- men. The analyses of the blood from the carotid, internal jugular, and vena cava have already been referred to in treating of the origin of the cholesterine. It will be remem- bered that there was a large quantity of this substance in the internal jugular, and but a small quantity in the carotid, showing that it was formed in the brain. "We now give the conclusion of these observations, which bears upon the sepa- ration of the cholesterine from the blood : Experiment I. — Specimens of blood were taken from the hepatic artery, portal vein, and hepatic vein, and a small quantity of bile from the gall-bladder. These specimens were treated in the manner already indicated ; i. e., evapo- rated and pulverized, extracted with ether, the ether evapo- rated, and the residue extracted with boiling alcohol, this evaporated, a solution of caustic potash added, and the specimen then subjected to a microscopical examination. Microscopical examination of the extract from the portal vein showed quite a number of crystals of cholesterine. These were observed after the fluid had nearly evaporated. Microscopical examination of the extract from the he- patic artery, made after the fluid had nearly evaporated, showed a considerable amount of cholesterine ; more than was observed in the preceding specimen. There were also observed a few crystals of stercorine. The first examination of the extract from the hepatic vein, which was made just before the potash was added, showed a number of fatty masses, with some crystals of ster- corine. The solution of potash was then added, and two days after, another careful examination was made, discov- 288 EXCRETION. ering nothing but fatty globules and granules. The watch- glass was then set aside and was examined eleven days after, when the fluid had entirely evaporated. At this examination, a few crystals of cholesterine were* observed for the first time. There were also a number of crystals of margaric and stearic acid. All the examinations of the extract from the bile showed cholesterine ; and the precipitate consisted, indeed, of this substance in a nearly pure state. Taking these experiments in connection with the first observations on the carotid and internal jugular, while the one series demonstrates pretty conclusively that cholesterine is formed in the brain, the other shows that it disappears, in a measure, from the blood in its passage through the liver, and is passed into the bile. In other words, it is formed in the nervous tissue, and is prevented from accumulating in the blood by its excretion by the liver. This suggests an inter- esting series of inquiries ; and this fact, fully substantiated, would be as important to the pathologist as to the physiolo- gist. But in order to settle this question, it is necessary to do something more than make an approximative estimate of the quantity of cholesterine removed from the blood by the liver. The quantity thus removed in the passage of the blood through this organ should be estimated, if pos- sible, as closely as the quantity which the blood gains in its passage through the brain. But this estimate is more diffi- cult. The operation for obtaining the specimens of blood, in the first place, is much more serious than that for collect- ing blood from the carotid and internal jugular. It is very difficult to take the unmixed blood from the hepatic vein ; and the exposure of the liver, if prolonged, may interfere with its eliminative function, in the same way that exposure of the kidneys arrests, in a few moments, the flow from the ureters. It is probable, however, that the administration of ether does not interfere with the elimination of choles- terine by the liver, as it does, apparently, with its formation EXCRETORY FUNCTION OF THE LIVER. 289 in the brain. Anaesthetics, we know, have a peculiar and special action on the brain, but do not interfere with the functions of vegetative life, such as secretion or excretion ; and, we may suppose, would not interfere with the depurative function of the liver. It is fortunate that this is the case, for the operation of taking blood from the abdominal ves- sels is immensely increased in difficulty by the struggles of an animal that is not under the influence of an anaesthetic. With the view of settling the question of the disappear- ance of a portion of the cholesterine of the blood in its passage through the liver, by an accurate quantitative analy- sis, we repeated the operation for drawing blood from the vessels which go into, and emerge from the liver. In the first trial the blood was drawn so unsatisfactorily, and the operation was so prolonged, that it was not thought worth while to complete the analysis, and the experiment was abandoned. In the following one we were more successful. Experiment II. — A good-sized bitch" (pregnant) was brought completely under the influence of ether, the abdo- men laid freely open, and blood drawn, first from the hepatic vein, and next from the portal vein. The taking of the blood was entirely satisfactory, the operation being done rapidly, and the blood collected without any admixture. A specimen of blood was then taken from the carotid, to repre- sent the blood from the hepatic artery. The three specimens of blood were then examined in the usual way for cholesterine, with the following results : Blood. Cholesterine. Cholesterine per grains. grains. 1,000 pts. Arterial blood 159-537 0'200 1-257 Portal vein 168-257 0*170 1-009 Hepatic vein 79*848 0*077 0'964 Percentage of loss in arterial blood in its passage through the liver... . 23'309 Do. do. the blood of the portal vein 4*460 This experiment proves positively, what there was good ground for supposing from Experiment I., that cholesterine 19 290 EXCRETION. is separated from the blood by the liver ; and here we may note, in passing, a striking coincidence between the analysis in a previous experiment, in which the blood was studied in its passage through the brain, and the one just mentioned, where the blood was studied in its passage through the liver. The gain of the arterial blood in cholesterine in passing through the brain was 23*307 per cent., and the loss of this substance in passing through the liver is 23*309 per cent. There must be, of course, the same quantity separated by the liver that is produced by the nervous system, it being formed, indeed, only to be separated by this organ, its for- mation being continuous, and its removal necessarily the same, in order to prevent its accumulation in the circulating fluid. The almost exact coincidence between these two quantities, in specimens taken from different animals, though not at all necessary to prove the fact just mentioned, is still very striking. It is shown by Experiment II. that the portal blood, as it goes into the liver, contains but a small percentage of cho- lesterine over the blood of the hepatic vein, while the per- centage in the arterial blood is large. The arterial blood is the mixed blood of the entire system ; and as it probably passes through no organ before it gets to the liver, that di- minishes its cholesterine, it contains a quantity of this sub- stance, which must be removed. The portal blood, coming from a limited part of the system, contains less cholesterine, though it gives up a certain quantity. In the circulation of the liver, the portal system largely predominates, and is necessary to other important functions of this organ, such as the production of sugar ; but soon after the portal vein enters the liver, its blood becomes mixed with that from the hepatic artery, and from this mixture the cholesterine is separated. It is only necessary that blood, containing a certain quantity of cholesterine, should come in contact with the bile-secreting cells, in order that this substance be sepa- rated. The fact that it is eliminated by the liver is proven EXCRETORY FUXCTIOX OF THE LIVEB. 291 with much less difficulty than that it is formed in the nervous system. In fact, its presence in the bile, and the necessity of its constant removal from the blood, consequent on its constant formation and absorption by this fluid, are almost sufficient in themselves to warrant the conclusion that it is removed by the liver. This, however, is put beyond a doubt by the preceding analyses of the blood going to and. coming from this organ. In treating of the composition of the feeces, we have con- sidered so fully the changes which the cholesterine of the bile undergoes in its passage down the intestinal canal, that it is not necessary to refer to this portion of the subject again.1 We have made but one examination of the quantity of ster- corine contained in the daily fecal evacuation, and assuming that the amount of cholesterine excreted by the liver in twenty-four hours is equal to the amount of stercorine found in the evacuations, the quantity is about ten and a half grains. This corresponds with the estimates of the daily quantity of cholesterine excreted, calculated from its propor- tion in the bile and the estimated daily amount of bile pro- duced by the liver. To complete the chain of the evidence leading to the conclusion that cholesterine is an excrementrtious principle, formed in certain of the tissues and eliminated by the liver, it is only necessary to show that it is liable to accumulate in the blood when the eliminating function of the liver is in- terrupted. It will be remembered that it was only after ex- tirpation of the kidneys, followed by accumulation of urea in the blood, that Prevost and Dumas were able to demon- strate the preexistence of this principle in the circulating fluid, and indicate the mechanism of its separation from the blood by the kidneys. This mode of study has been applied to certain of the elements of the bile, though without suc- cess; for Muller, Kunde, Lehmann, and Moleschott, who have extirpated the livers from frogs, looked in the blood 1 See vol. ii., Digestion, p. 399, et seq. 292 EXCRETION. only for the biliary salts.1 "We have not been able to re- peat these experiments on frogs, and analyze the blood for cholesterine, but we have arrived at very positive results in the study of the blood in diseased conditions of the liver, that are interesting alike to the physiologist and the pathologist. It has long been recognized that cases of ordinary ictei as are not of a grave character, while there are cases in which the jaundice, though less marked as regards color, is a very different condition. Chemists have analyzed the blood, in the hope of explaining this difference by the presence, in the grave cases, of the taurocholate and glycocholate of soda; but their failure to detect these principles leaves the ques- tion still uncertain. The real distinction, arguing from purely theoretical considerations, would lie in the propo- sition that, in cases of simple jaundice, there is merely a resorption from the biliary passages of the coloring matter of the bile, and in grave cases — which are almost invaria- bly fatal — there is retention of cholesterine in the blood. We have not been able, on account of the insolubility of cholesterine, to observe the effects of injecting it into the blood-vessels, but we have had an opportunity of making an examination of the blood of a patient in the last stages of cirrhosis of the liver, accompanied with jaundice, and com- pared it with an examination of the blood of a patient suffer- ing from simple icterus. Both of these patients had decolo- ration of the faeces ; but in the first the icterus was a grave symptom, accompanying the last stages of disorganization of the liver ; while in the latter it was simply dependent on duodenitis, and the prognosis was favorable and verified by the result. As icterus accompanying jaundice is of very in- frequent occurrence, we were fortunate in having an oppor- tunity of comparing the two cases. Without giving in full the details of these cases and the examinations, which are contained in our original memoir 1 See p. 267. EXCRETORY FUNCTION OF THE LIVER. 293 on cholesterine,1 it is sufficient here to state the main results of the examinations of the blood and faeces. In the case of simple jaundice from duodenitis, in which there was no great disturbance of the system, a specimen of blood, taken from the arm, presented undoubted evidences of the coloring matter of the bile, but the proportion of cholesterine was not increased, being only 0*508 of a part per thousand. The faeces contained a large proportion of saponifiable fat, but no cholesterine or stercorine. In the case of cirrhosis with jaundice, there were ascites and great general prostration. This patient died a few days after the blood and faeces had been examined, and the liver was found in a condition of cirrhosis, with the liver-cells shrunken, and the gall-bladder contracted. In this case the blood contained 1*850 pts. of cholesterine per thousand, more than double the largest quantity we had ever found in health. The faeces contained a small quantity of stercorine. Inasmuch as cases frequently present themselves in which there are evidences of cirrhosis of the liver, with little, if any, constitutional disturbance, while others are attended with grave nervous symptoms, it seemed an interesting ques- tion to determine whether it be possible for cholesterine to accumulate in the blood without the ordinary evidence of jaundice. WQ had an opportunity of examining the blood in two strongly-contrasted cases of cirrhosis, in neither of which was there jaundice. One of these patients had been tapped repeatedly (about thirty times), but the ascites was the only troublesome symp- tom, and his general health was pretty good. In this case the proportion of cholesterine in the blood was only 0*246 of a part per thousand, considerably below the quantity that we had found in health. The other patient had cirrhosis, but was confined to the bed and was very feeble. The proportion of cholesterine in 1 American Journal of the Medical Sciences, Philadelphia, 1862, New Series, vol. xliv., p. 349, et seq. 294 EXCRETION. the blood in this case was 0*922 of a part per thousand, a lit- tle above the largest proportion we had found in health. Like the examinations of the blood in the three cases of paralysis, these pathological observations are not sufficient, in themselves, to establish the function of cholesterine ; but taken in connection with our other experiments, they fully confirm our views with regard to the excretory function of the liver. It is pretty certain that organic disease of the liver, accompanied with grave symptoms generally affecting the nervous system, does not differ in its pathology from cases of simple jaundice in the fact of retention of the bili- ary salts in the blood ; but these grave symptoms, it is more than probable, are due to a deficiency in the elimination of cholesterine — the true excrementitious principle of the bile — and its consequent accumulation in the system. Like the accumulation of urea in structural disease of the kidney, this produces blood-poisoning ; and we have characterized this condition by the name of Cholestercemia, a name ex- pressing a pathological condition, but at the same time indi- cating the physiological relations of cholesterine. CHAPTEE X. PRODUCTION OF SUGAR IN THE LIVER. Evidences of a glycogenic function in the liver — Processes for the determination of sugar — Fehling's test for sugar — Examination of the blood of the portal system for sugar — Inosite — Examination of the blood of the hepatic veins for sugar — Does the liver contain sugar during life ? — Characteristics of liver-sugar — Mechanism of the production of sugar in the liver — Glyco- genic matter — Process for the extraction of glycogenic matter — Variations in the glycogenic function — Production of sugar in foetal life — Influence of digestion and of different kinds of food on glycogenesis — Influence of the nervous system, etc., on glycogenesis — Artificial diabetes — Influence of the inhalation of anaesthetics and irritating vapors on glycogenesis — Destina- tion of sugar — Alleged production of fat by the liver — Changes in the albuminoid and the corpuscular elements of the blood in their passage through the liver. IT was formerly supposed that the chief and the only important office of the liver was to produce bile, and all physiological researches into the functions of this organ were then directed to the question of the uses of the biliary secre- tion ; but in 1848, it was announced by Bernard that he had discovered in the liver a new and important function, and he proceeded to show, by an ingeniously conceived series of experiments, that the liver is constantly producing sugar of the variety that had long been recognized in the urine of persons suffering from diabetes mellitus. The great physiological and pathological importance of the discovery, attested, as it was, by experiments which seemed to be posi- tively conclusive in their results, excited the most profound scientific interest. During the present century, indeed, there 296 SECRETION. have been few physiological questions that have attracted so much attention ; and the observations of Bernard were soon repeated, modified, and extended by experimentalists in dif- ferent parts of the world. In 1857, Bernard discovered a sugar-forming material in the liver, analogous in its compo- sition and properties to starch ; and this seemed to complete the history of glycogenesis. Shortly after the publication of the glycogenic theory, it was found that other changes were effected in the blood in its passage through the liver, and physiologists then under- stood, for the first time, how glandular organs might pro- duce secretions, and yet not discharge them into excretory ducts ; and this, indeed, pointed the way to the explanation of the function of the ductless glands. It is perfectly correct to say that the liver secretes sugar ; but the secretion, in this instance, is carried away by the blood ; and from this point of view, the liver is a ductless gland. It is evident, therefore, that even after having studied fully the secre- tion and the physiological relations of the bile, we have to consider other glandular functions of the liver, hardly less important. Evidences of a Glycogenie Function in the Liver. — The proof of the glycogenic function of the liver rests upon the fact, experimentally demonstrated by Bernard, that in all animals, the blood coming from the liver by the hepatic veins contains sugar ; and that the presence of this principle here is not dependent upon the starch or sugar of the food. Bernard assumes to have proven that, in carnivorous ani- mals, never having taken starch or sugar into the aliment- ary canal, except in the milk, there is no sugar in the blood of the portal vein as it passes into the liver ; but, under nor- mal conditions, the blood of the hepatic veins always contains sugar. Having examined the blood from various parts of the body, and made extracts of all the other tissues and organs, Bernard was unable to find sugar in any other situations PRODUCTION OF SUGAR IN THE LIVER. 297 than the liver and the blood coming from the liver. As the blood from the liver is mixed in the vena cava with the blood from the lower extremities, and in the right side of the heart, with the blood from the descending cava, the amount of sugar is proportionately diminished in passing from the liver to the heart. It was found that the sugar generally disappeared in the lungs, and did not exist in the blood of the arterial sys- tem. Assuming that these statements have been sustained by experimental facts, there can be no doubt that the liver produces or secretes sugar ; that this secretion is taken up by the blood ; and that the sugar is destroyed in its passage through the lungs. The question of the production of sugar in the economy has given rise to a great deal of discussion, and the experi- ments of Bernard have been repeated very extensively. Many physiologists of high authority have been able to verify these observations in every particular; but others have published accounts of experiments which seem to dis- prove the whole theory. There can be no doubt of the fact that sugar may, under certain conditions, be produced de novo in the organism. Cases of diabetes, in which the discharge of sugar by the urine continues, to a certain extent, when no starch or sugar is taken as food, are conclusive evidence of this- proposition. It is a fact equally well established, that the sugar taken as food and resulting from the digestion of starch is consumed in the organism, and is never discharged. The fact with re- gard to diabetes shows, then, that it is not impossible, when no sugar or starch is taken as food, that sugar should be pro- duced in the body ; and the failure to find the sugar of the food in the blood or excreta shows that this principle is nor- mally destroyed or consumed in the organism. It only re- mains, therefore, to determine whether the production of sugar in diabetes be a new pathological process, or merely the exaggeration of a physiological function. We have so often repeated and verified the observations 298 SECRETION. of Bernard, both in experiments made for purposes of inves- tigation and in public demonstrations, that we can entertain no doubt with regard to the glycogenic function of the liver. We have, however, made some late observations, which have modified our views concerning the mechanism of glycogene- sis ; but the fact of the production of sugar in the healthy organism is not affected. Notwithstanding that it seems so easy to verify these experiments, there is, particularly in Great Britain, a pretty wide-spread conviction, that the liver does not produce sugar during life, and that the sugar found by Bernard and others is due to post-mortem action. This view is based chiefly on the observations of Dr. Pavy, of Guy's Hospital ; but it has been adopted by some authori- ties in Germany and in France. In this state of the ques- tion, it will not be sufficient to detail merely the experi- ments that seem to demonstrate the glycogenic function, but it will be necessary to examine these observations critically, and compare them with experiments which lead, apparently, to opposite conclusions ; for it is but fair to admit that the observations of Pavy seem to be as accu- rate, and, at the first blush, as conclusive as those of Bernard. The experiments of Bernard were published for the first time in 1848,1 but were afterward much extended, and pub- lished as a thesis, in 1853." The most accessible account of the original experiments is in the first volume of his published lectures, delivered at the College of France, in 1854-'55.8 In addition, many of the volumes of lectures published from time to time by Bernard contain new obser- 1 BERNARD, De Vorigine du sucre dans V economic animale. — Archives generates de medecine, Paris, 1848, 4me serie, tome xviii., p. 303, et seq. 2 BERNARD, Recherches sur une nouvelle fonction du foie, consider e comme organe producteur de matiere sucree chez Fhomme et les animaux. These presentee d la Faculte des Sciences de Paris pour obtenir le grade de Docteur es Sciences Naiu- relles, Paris, 1853. 8 BERNARD, Lecons de physiologie experimentale. Cours du semestre tfhiver, 1854-'55, Paris, 1855. PRODUCTION OF SUGAR IX THE LIVER. 299 vations upon the glycogenic function ; ' and in the Journal de la physiologic 1859, is an account of the formation of sugar in the foetus,2 followed by some reflections upon its relations to the development of the tissues.3 In the account of the discovery given by Bernard, it appears that he first sought for the situation in the body where the sugar derived from alimentary substances is de- stroyed. With this end in view, he fed a dog for seven days with articles containing a large proportion of sugar and starch. On analyzing the blood from the portal system, he found a large proportion of sugar ; and he also found it in the blood of the hepatic veins. As a counter-experiment, he fed a dog for seven days exclusively on meat, and then looked for sugar in the blood of the hepatic veins; and, to his surprise, found it in abundance. This experiment he repeated frequently with the greatest care, and always with the same result; and he concluded that sugar was formed in the liver, and was contained in the blood com- ing from this organ independently of the diet of the ani- mal. He afterward made extracts of the substance of the liver and of the other tissues, and found that this organ always contained sugar, while it was not to be detected in any other organ or tissue in the economy.4 In subsequent experiments, it was demonstrated that the livers of nearly all classes of animals contained sugar, and that it existed also in the human subject.5 He made observations, also, upon the 1 BERNARD, Lemons sur les effets des substances toxiques et medicamenteuses, Paris, 1857, p. 445, et seq. Leconssur la, physiologic et la pathologic du systeme nerveux, Paris, 1858, tome i., p. 397, et seq., and tome ii., p. 544, et seq. Lecons sur les proprittes physiologiques et les alterations palhologiques des liquidesde Vorganisme, Paris, 1859, tome ii., p. 88, et seq. 3 BERNARD, Sur une nouvelle fonction du placenta. — Journal de la physiologic, Paris, 1859, tome ii., p. 31, et seq. 3 Idem, p. 326, et seq. 4 BERNARD, These, Paris, 1853, pp. 13, 14. 5 BERNARD, op. cit., p. 31, et seq. The examinations of the liver of the human subject for sugar were made by Bernard in executed criminals, soon after death, 300 SECRETION. mechanism of its production, its disappearance in the blood circulating through the lungs, and the various influences which modify the glycogenic function. These points will be considered in their appropriate place ; and we will now proceed, after examining the processes for the determination of sugar, to take up, seriatim, the following questions : 1. The absence of sugar from the blood of the portal system in animals that have taken neither starch nor sugar into the alimentary canal. 2. The presence of sugar in the blood as it comes directly from the liver by the hepatic veins, independently of saccha- rine or amylaceous food. 3. The mechanism of the production of sugar by the liver. Processes for the Determination of Sugar. — In Bernard's first observations on the liver, he applied the fermentation- test to a simple decoction of the hepatic substance, and ob- tained unmistakable evidences of sugar. In operating upon perfectly fresh and normal blood, the addition of water and nitration frequently sufficed to procure a clear solution, to which the ordinary copper-tests could be applied ; but the most satisfactory method of making a clear extract was to boil the blood with water and an excess of sulphate of soda. By this means a clear extract can be obtained, containing, it is true, a large proportion of sulphate of soda ; but this salt, fortunately, does not interfere with the tests. Later, Bernard decolorized his solutions and extracts by making the liquid into a paste with animal charcoal and filtering. We have long been in the habit of employing both of these methods ; but when we have simply desired to determine the presence or absence of sugar, the process with the sulphate of soda has proved the most convenient. In delicate examinations, and in persons killed suddenly while in perfect health. An opportunity lately occurred in Albany for the examination of the liver in a man killed suddenly. The analysis was made by the late Prof. Howard Townsend, who fully confirmed the observations of Bernard (TOWNSEND, Glycogenic Function of the Liver, Albany, 1864). PRODUCTION OF SUGAR IN THE LIVER. 301 however, we have generally used animal charcoal. We have used both methods in decolorizing the decoction of the liver- substance, as well as in operating upon the blood. In ordinary examinations, Trommer's test is sufficiently delicate ; but it is not so sensitive nor so convenient as some of the standard test-solutions. We have been in the habit of using, for the determination of sugar in the urine, a modi- fication of Fehling's test, which is also very convenient for examinations of the blood and liver-extract. This may also be used for quantitative examinations ; but, like all of the standard solutions, it presents the inconvenience of under- going alteration by keeping, so that it is desirable to use it freshly-made for each series of examinations. We have suc- ceeded in obviating this difficulty, however, by the following modification in its preparation ; and, made in this way, it is probably the most convenient test that can be used in the examination of any of the animal fluids for sugar. Fehling^s Test for Sugar. — The modification in the test consists simply in preparing three separate solutions, which are to be mixed just before using, as follows : Solution of crystallized sulphate of copper, 90£ grains in an ounce of distilled water. Solution of neutral tartrate of potash, 36i grains in an ounce of distilled water. Solution of caustic soda, specific gravity 1*12. These solutions are to be kept in separate bottles, and used as follows : Take half of a fluidrachm of the copper-solution, add half a fluidrachm of the solution of tartrate of potash, and add the solution of caustic soda, to make three fluidrachms. It is important to measure the copper-solution with especial accuracy for quantitative analyses, as the quantity of copper decomposed indicates the amount of sugar.1 1 The above modification of Fehling's test consists simply in making and keeping the solutions separately, and mixing them for use in the proportions 302 SECRETION. To apply this test in ordinary qualitative analyses, heat a small portion of the test-liquid to the boiling point in a test-tube, and add the suspected fluid, drop by drop. If sugar be present in even a moderate quantity, a dense yel- lowish precipitate of the suboxide of copper will be produced after adding a few drops; and if the liquid be added to about the same volume as the test, and the mixture be again raised to the boiling point, without producing any deposit, it is certain that no sugar is present. The estimation of the quantity of sugar in any liquid depends upon the fact that two hundred grains of the test-liquid is decolorized by ex- actly one grain of glucose. To apply this test, measure off in a glass, specially graduated for the purpose, two hundred grains of the solution ; put this into a flask, with about twice its volume of distilled water, and boil ; when boiling, add the suspected solution, little by little, from a burette gradu- ated in grains (raising the mixture to the boiling point each time and afterward allowing the precipitate to subside), until the blue color is completely discharged ; by then reading off the number of grains of the saccharine solution that has been added, the proportion of sugar may be readily calculated. If the solution be suspected to contain a considerable quan- tity of sugar, the estimate may be more accurately made by diluting it to a known degree, say with nine parts of water, and adding this diluted mixture to the test-liquid.1 Bernard, in his quantitative examinations, employed a test-liquid known as Barreswil's solution, but the process is essentially the same as the one we have just described. One advantage of boiling the standard liquid before applying the required. The original formula, given by Roberts, reduced to English grains, is as follows : Sulphate of copper, 90i grains ; Neutral tartrate of potash, 364 grains ; Solution of caustic soda, sp. gr. 112, four fluidounces. Add water to make exactly six fluidounces. — (ROBERTS, A Practical Treat^e on Urinary and Renal Diseases, Philadelphia, 1866, p. 147.) 1 ROBERTS, op. cit., p. 147. PRODUCTION OF SUGAR IN THE LIVER. 303 test is that, when it is altered so as to be unreliable, the yellow precipitate is thrown down by simple boiling. In making delicate examinations, it is best always, when this occurs, to make a fresh solution.1 Examination of the Blood of the Portal System for Sugar. — If starch or sugar be taken into the alimentary canal, it is well known that sugar is always to be found, during absorption, in the blood of the portal system ; but in the carnivorous animals, that have been fed entirely upon meat, no sugar is to be found in the portal blood. Bernard is very definite upon this point, and indicates a liability to error when the operation of tying the portal vein has not been skilfully performed, and when blood, containing sugar, is allowed to regurgitate from the substance of the liver. In taking the blood just before it enters the liver, it is necessary to apply a ligature to the vessels as they penetrate at the transverse fissure. This should be done quickly, and the opening into the abdominal cavity should be small. Other- wise, as the vessels have no valves, we are liable to have re- flux of blood from the liver. We have frequently performed the experiment, after the method described by Bernard, making a small opening in the linea alba a little below the ensiform cartilage, just large enough to admit the forefinger of the left hand ; introducing the finger, and feeling along the concave surface of the liver until we are able to seize the vessels; then passing in an aneurism-needle, and con- stricting the vessels before the abdomen is widely opened^ when a firm ligature is applied. When this step of the operation has been satisfactorily performed, we have never found a trace of sugar in the extract from the blood of the portal system, in animals that have been fed upon nitrogen- ized matter alone. Among those who have refused to admit the glycogenic 1 The properties of the test-liquid may be restored sufficiently for ordinary qualitative examinations by adding a little more caustic soda and filtering. 304: SECKETION. function of the liver, there have been few who have denied the proposition that the portal blood does not contain sugar except during absorption of this principle from the alimen- tary canal. Figuier, who made an elaborate series of inves- tigations on this subject with the view of invalidating the experiments of Bernard, assumed that this proposition was incorrect, and that the portal blood carries sugar to the liver during the digestion of starchy and saccharine matters, where it is retained,1 and, furthermore, that there is sugar in the blood of the portal vein during the digestion of raw meat.2 From these and other observations, Figuier concludes that the liver does not produce sugar, but that the sugar, brought to this organ by the portal blood, is here stored up, to be passed, little by little, into the blood of the hepatic veins.3 These conclusions cannot be accepted, for the reason that the evidence of the presence of sugar in the portal blood of animals during the digestion of meat is far from satisfac- tory. A commission of the French Academy of Sciences, composed of MM. Dumas, Pelouze, and Rayer, after a careful examination of the extracts of the portal blood presented by M. Figuier, decided that the evidence of the presence of sugar was insufficient, and came to the conclusion "that sugar was not appreciable in the blood of the portal vein of a dog fed on raw meat." * This seems to settle the question, as far as the observations of M. Figuier are concerned, the report of the commission being pretty generally accepted as con- clusive.6 1 FIGUIER, Memoire sur Vorigine du sucre dans le foie et sur T existence normale du sucre dans le sang de Vhomme et des animaux. — Comptes rendus, Paris, 1855, tome xi, p. 228. 2 FIGUIER, Deuxieme memoire d propos de la fonction glycogenique du foie. — Comptes rendus, Paris, 1855, tome xl., p. 674. 3 FIGUIER, Troisieme memoire sur la fonction glycogenique du foie. — Comptes rendus, Paris, 1855, tome xli., p. 352. 4 DUMAS, Rapport sur divers memoires relatifs auxfonctions du foie. — Comptes rendus, Paris, 1855, tome xl., p. 1281. 5 BERARD, Note additionnelle au memoire lu d V Academic dans la seance du 19 mai, 1857. — Gazette hebdomadaire, Paris, 1857, tome iv., p. 414. PRODUCTION OF SUGAR IN THE LIVER. 305 The only other question that has been raised with regard to the possible presence of sugar or sugar-forming matter in the blood of the portal vein has been that inosite (C12HiaO12), a substance discovered by Scherer in the muscular tissue of the heart,1 might be introduced into the portal blood with the animal food. But even if inosite should be contained in food and be detected in the blood of the portal system, it cannot possibly have any thing to do with the glycogenic process, and it is not known that it has any relations to the sugars. Anhydrous inosite is isomeric with anhydrous glu- cose, but it does not respond to any of the copper-tests, and is unfermentable.a In view of all these facts, there can be no doubt that the blood carried to the liver by the portal vein does not contain sugar, in animals fed solely upon nitrogenized matters. The quantity of blood carried to the liver by the hepatic artery is insignificant ; and, although the arterial blood may tem- porarily contain a trace of sugar, as we shall see further on, this need not complicate the question under consideration, as the presence of sugar in the blood of the hepatic artery is ex- ceptional, and its proportion, when it exists, is very minute. Examination of the Blood of the Hepatic Veins for Sugar. — It is upon this question that the whole doctrine of the sugar-producing function of the liver must rest. If it can be proven that the blood, taken from the hepatic veins during life or immediately after death, normally contains sugar, while the blood distributed to the liver contains neither sugar nor any substance that can be immediately converted into sugar, the inevitable conclusion is that the liver is a sugar-producing organ. We will, consequently, examine this part of the question with the care which its importance demands. 1 SCHERER, Ueber eine neue, aus dem Muskelfleische, gewonnene Zuckerart. — Annalen der Chemie und Pkarmacie, Heidelberg, 1850, Bd. Ixxiii., S. 322, et seq. 8 LEHMANN, Physiological Chemistry, Philadelphia, 1855, vol. i., p. 264. 20 306 SECRETION. The proposition that the blood from the hepatic veins does not contain sugar during life and health cannot be sustained by actual experiment. Observers may say that the quantity is very slight, but its existence in this situation, indepen- dently of the kind of food taken, cannot be denied. Dr. Pavy, who is the originator of the theory that the sugar found in the liver and in the blood coming from the liver is due to a post-mortem change, nowhere states that he has taken the blood from the hepatic veins and failed to find sugar. He states that he has found the blood taken from the right side of the heart by catheterization, in a living animal, " scarcely at all impregnated with saccharine mat- ter," l but he does not deny its presence in small quantity. In twelve examinations made by Dr. M'Donnell, of Dublin, traces of sugar were found in five specimens of blood taken from the right auricle by catheterization, in the living ani- mal, and no sugar was detected in seven.8 It must be re- membered, in considering these experiments, that the blood of the right side of the heart is the mixed blood from the entire body ; and, assuming that the hepatic blood is con- stantly saccharine, the quantity in the blood of the right heart would not be very great. In opposition to these experiments, which are only par- tially negative, we have the following results of examina- tions of the blood of the hepatic veins and of the right side of the heart taken as nearly as possible under normal condi- tions. To demonstrate the absence of sugar in the portal vein and its constant presence in the hepatic veins in dogs fed ex- clusively on meat, Bernard employed the following process : The animal was killed instantly by section of the medulla cblongata. A small opening was then made into the abdo- men, just large enough to admit the finger and to enable 1 PAVY, Researches on the Nature and Treatment of Diabetes, London, 1862, PP- 44, 46. 2 M'DONNELL, Observations on the Functions of the Liver, Dublin, 1865, p. 4. PRODUCTION OF SrGAK IX THE LIVER. 307 him to seize the portal vein as it enters at the transverse fissure, and apply a ligature. The abdomen was then freely opened and a ligature applied to the vena cava just above the renal veins, to shut off the blood from the posterior extremi- ties. The chest was then opened, and a ligature was applied to the vena cava just above the opening of the hepatic veins. Operating in this way, blood may be taken from the portal system before it enters the liver, and from the hepatic veins as it passes out. In the blood from the portal system no sugar is to be found, but its presence is unmistakable in the blood from the hepatic veins.1 To avoid disturbing the cir- culation in the liver, and in order to collect from the hepatic veins as large a quantity of blood as possible, Bernard modi- fied the experiment, in some instances, by introducing into the vena cava in the abdomen a double sound, the extremity of which is provided with a bulb of India-rubber. This was pushed into the vein above the diaphragm ; and by inflating the bulb, the vein was obstructed above the liver, and the blood could be collected through one of the canulse, as it came directly from the hepatic vessels. Bernard never failed to determine the presence of sugar in these specimens of blood, employing a number of different processes, includ- ing the fermentation-test and even collecting the alcohol.8 To complete the proof of the existence of sugar in the blood coming from the liver, Bernard demonstrated its presence in blood taken from the right auricle in a living animal. He O O also showed that during digestion the whole mass of blood contained sugar, but the quantity was greater in the right side of the heart than in the arterial system.8 It is unnecessary to cite all the authorities that have confirmed the observations of Bernard. Shortly after these 1 BERNARD, Recherches sur une nouvdle fondwn du foie, Paris, 1853, p. 56. 2 BERNARD, Lemons de physiologic experimentale, Paris, 1855, p. 494. The reader will find here a description, with a figure, of the instrument mentioned in the text, which is very ingenious. 3 Op. tit., p. 120. 308 SECRETION. experiments were published, Lehmann,1 Frerichs,8 and many others verified their accuracy. Bernard gives in full the experiments of Poggiale8 and of Leconte,4 the results of which were identical with his own. He gives, also, in one of his later works, the proportions of sugar in the blood of the hepatic veins, obtained by Lehmann, Schmidt, Poggiale, and Leconte; no sugar being found in the blood of the por- tal system.6 "We have ourselves made a number of experi- ments with a view of harmonizing, if possible, the discordant observations of Bernard and Pavy, and have examined the blood from the hepatic veins for sugar, taking the speci- mens under what seemed to be strictly physiological condi- tions. In one of these published experiments, blood was taken from the hepatic veins of a large dog, fully grown and fed regularly every day, but not in digestion at the time of the experiment, and the operation lasted only seventy seconds. No anaesthetic was employed. The extract of this specimen of blood, treated with Fehling's test-liquid, presented a well-marked deposit of the oxide of copper, revealing unequivocally the presence of a small quantity of sugar.9 This has been the invariable result in numerous experiments and class-demonstrations made since 1858 ; and since the experiments just referred to were published, we have verified the observation with regard to the hepatic blood, keeping the animal perfectly quiet before the opera- 1 LEHMANN, Physiological Chemistry, Philadelphia, 1855, vol. i., p. 257. 9 FRERICHS, Verdauung. — WAGNER'S Handworterbuch der Physiologic, Braun- schweig, 1846, Bd. iii., erste Abtheilung, S. 831. 3 POGGIALE, La matiere sucree se forme-t-elle par V action digestive, dans lefoie et dans le torrent circulatoire ? in BERNARD, Lemons de physiologic experimentale, Paris, 1855, p. 497. 4 LECONTE, Recherches sur la fonction glucogenique du foie, Idem, p. 499. 5 BERNARD, Liquides de Vorganisme, Paris, 1859, tome ii., p. 98. 6 FLINT, Jr., Experiments undertaken for the Purpose of reconciling some of the Discordant Observations upon the Glycogenic Function of the Liver. — New York Medical Journal, 1869, vol. viii., p. 381. These experiments will be referred to again in treating of the question of the existence of sugar in the substance of the liver during life. PRODUCTION OF SUGAR IN THE LIVER. 309 tion, avoiding the administration of an anaesthetic, and taking the blood so rapidly that no sugar could be formed by the liver post mortem. These experiments leave no doubt of the fact that, during life and in health, the blood, as it passes through the liver and is discharged by the hepatic veins into the vena cava, contains sugar, which is formed by the liver, independently of the sugar and starch taken as food. Does the Liver contain Sugar normally during Life f — This is the only question upon which the results of reliable experiments have been entirely opposite. Bernard made the greater part of his observations by analyzing the substance of the liver ; and he arrived at most of his conclusions with re- gard to the variations in the glycogeuic function, from esti- mates of the proportion of sugar in the liver under different conditions. For many years we have been in the habit of re- peating these experiments, with like results, and never failed to find sugar, under normal conditions of the system. "We were formerly in the habit of making the demonstrations of the formation of sugar in the liver upon animals that had been etherized ; and then we always obtained a brilliant pre- cipitate from the clear extract of the substance of the liver boiled with the test-liquid. The experiment was performed in this way before we had acquired sufficient dexterity to seize the portal vein readily and to go through with the necessary manipulations with rapidity. "We subsequently made the operation by first suddenly breaking up the me- dulla oblongata, then making a small incision into the abdominal cavity, seizing the portal vein instantly, and following out the remaining steps of the experiment without delay. In this way, although sugar was always found in the blood of the hepatic veins, we frequently failed to obtain a distinct reaction in the extract of the liver ; and it seemed, indeed, that the more accurately and rapidly the operation was performed, the more difficult was it to detect sugar in the hepatic substance. 310 SECRETION. It seems probable, in reflecting upon these facts, that, inasmuch as no one has assumed that the actual quantity of sugar produced by the liver is very considerable, and as a large quantity of blood (in which the sugar is very soluble) is constantly passing through the liver, precisely as we pass water through its vessels to remove the sugar, the sugar might be washed out by the blood as fast as it is formed ; and really the liver might never contain sugar in its sub- stance, as a physiological condition, although it is constantly engaged in its production. We know that the characteristic elements of the various secretions proper are produced in the substance of the glands, and are washed out at the proper time by liquid derived from the blood, which circu- lates in their substance during their functional activity in very much greater quantity than during the intervals of secretion. ISTow, the liver-sugar may certainly be regarded as an element of secretion ; and, possibly, it may be com- pletely washed out of the liver, as fast as it is formed, by the current of blood; the hepatic vein, in this regard, serving as an excretory duct. To put this hypothesis to the test of experiment, it was necessary to obtain and analyze a specimen of the liver in a condition as near as possible to that under which it exists in the living organism ; and in carrying out this idea, we instituted the following experiments : Experiment I. — A medium-sized dog, full grown, in good condition, not in digestion, was held upon the operat- ing-table by two assistants, and the abdomen was widely opened by a single sweep of the knife. A portion of the liver, weighing about two ounces, was then excised and immediately cut into small pieces, which were allowed to fall into boiling water. The time from the first incision until the liver was in the boiling water was twenty-eight seconds. An excess of crystallized sulphate of soda was then added, and the mixture was boiled for about five min- utes. It was then thrown upon a filter, and the clear fluid PRODUCTION OF. SUGAR IN THE LIVER. 311 that passed through was tested for sugar by Trommer's test. The reaction was doubtful, and presented no marked evidence of sugar. Experiment II. — A medium-sized dog, in the same con- dition as the animal in the first experiment, was held upon the table, and a portion of the liver excised, as above de- scribed. The whole operation occupied twenty-two seconds. But ten seconds elapsed from the time the portion 'of the liver was cut off until it was in the boiling water. It was boiled for about fifteen minutes, made into a paste with animal charcoal, and thrown upon a filter. The clear fluid that passed through was tested for sugar by Trommer's test. There was no marked evidence of sugar. Experiment III. — A large dog, full grown, and fed regu- larly every day, but not in digestion at the time of the experiment, was held firmly upon the table. This dog had been in the laboratory about a week, and was in a perfectly normal condition. The abdominal cavity was opened, and a piece of the liver cut off and thrown into boiling water, the time occupied in the process being ten seconds. Be- fore the liver was cut up into the boiling water, the blood was rinsed off in cold water. The liver was boiled for about seventeen minutes, mixed with animal charcoal, and the whole thrown upon a filter. Immediately after cutting off a portion of the liver and throwing it into boiling water, the medulla oblongata was broken up ; a ligature was applied to the ascending vena cava, just above the renal veins ; the chest was opened, and a ligature applied to the vena cava, just above the opening of the hepatic veins. A specimen of blood was then taken from the hepatic veins. This portion of the operation occu- pied not more than one minute. A little water was added to the blood, which was boiled briskly, mixed with animal charcoal, and thrown upon a filter. The liquid that passed through from both specimens was perfectly clear. While the filtration was going on, Fehling's test-liquid 312 SECRETION. was made up, so as to be perfectly fresh. The two liquids were then carefully tested for sugar. The extract of the liver presented not the slightest trace of sugar. The extract from the blood of the hepatic veins presented a well-marked deposit of the oxide of copper, revealing unequivocally the presence of a small quantity of sugar. Experiment IV. — This experiment was made upon a medium-sized dog, in full digestion of meat. The medulla oblongata was broken up ; the portal vein was tied through a small opening in the abdomen • and the abdomen was then widely opened, and a portion of the liver excised, rapidly rinsed, and cut up into boiling water. The length of time that elapsed between breaking up the medulla and cutting up the specimen of liver into the boiling water was one minute. The vena cava was then tied above the renal veins, the chest opened, and the cava again tied above the hepatic veins. Blood was then taken from the hepatic veins, about an equal bulk of water was added with an excess of the crystallized sulphate of soda, and the mixture was boiled. A portion of the portal blood and the decoction of the liver were then treated in the same way, and the three specimens filtered. The clear extracts were then tested with Fehling's liquid, with the following result : There was no sugar in the portal blood. There was no sugar in the extract of the liver. There was a marked reaction in the extract of the blood from the hepatic veins, the precipitate rendering the whole solution bright yellow and entirely opaque. This experiment was made in the presence of the class, at the Bellevue Hospital Medical College, January 4, 1869. The importance of the question under consideration and its present unsettled condition are, we hope, sufficient to justify the introduction of the details of the preceding experiments. They were undertaken with the view of har- PRODUCTION OF SUGAR IN THE LIVER. 313 monizing, if possible, the facts brought forward by different experimentalists. It is difficult to imagine how any observer, so well known and accurate as Dr. Pavy, could assert positively, as the result of personal examination, that the liver does not contain sugar when examined immediately after its removal from the living body, when Bernard and so many others have demonstrated its presence in this organ in large quan- tity. Yet such was the result of all the experiments of Pavy,1 and the same conclusion was arrived at by M'Don- nell,a and afterward by Meissner and Jaeger, and by Schiff.3 The elegant experiment of Bernard, showing that sugar is formed in a liver removed from the body and washed sugar-free by a stream of water passed through its vessels,4 demonstrated the possibility of the production of sugar post- mortem, so strongly claimed by Pavy as the only condition under which it is ever formed ; still, it does not seem pos- sible to deny the sugar-producing function of the liver, in view of the conclusive experimental proof of the constant presence of glucose in the blood of the hepatic veins. From our own experiments we have come to the conclu- sion that Dr. Pavy and those who adopt his views cannot consistently deny that sugar is constantly formed in the liver 1 PAVY, Researches on Sugar Formation in ike Liver. — Philosophical Trans- actions, London, 1860, p. 595, and Researches on the Nature and Treatment of Diabetes, London, 1862, p. 52, et seq. 2 M'DONNELL, Observations on the Functions of the Liver, Dublin, 1865, p. 4, et seq. 3 SCHIFF, Nouvelles recherches sur la glycogenie animale. — Journal de Vanatomie, Paris, 1866, tome Hi., p. 354, et seq. Meissner and Jaeger and Schiff took por- tions of the liver from living animals and from animals at the instant they were killed by section of the medulla oblongata, plunged the tissue immediately into boiling water, and invariably failed to find sugar in the extract. They did not, however, recognize sugar in the blood coming from the liver, as we did in our own experiments. 4 BERNARD, Sur h mechanisme de la formation du sucre dans lefoie. — Comptes rendus, Paris, 1855, tome xli., p. 461, and Lemons sur les effets des substances toxiqucs et medicamenteuses, Paris, 1857, p. 453. 314 SECEETION. and discharged into the blood of the hepatic veins ; nor can Bernard and his followers ignore the fact that the liver does not contain sugar during life ; although, as has been shown by Pavy, and more specifically by M'Donnell,1 sugar ap- pears in the liver in great abundance soon after death. In the experiments that we have just detailed, which are simply typical examples of numerous unrecorded obser- vations, we attempted to verify the observations of Pavy without losing sight of the facts observed by Bernard, and to verify the experiments of Bernard in the face of the apparently contradictory statements of Pavy. When an animal is in perfect health, has been kept quiet before the experiment, and a piece of the liver is taken from him by two sweeps of the knife, the blood rinsed from it and the tissue cut up into water already boiling, the whole operation occupying only ten seconds ( as was the case in Experiment III. ), the liver is as nearly as possible in the condition in which it exists in the living organism. As this was done repeatedly in animals during digestion and in the intervals of digestion, and an extract thoroughly made without finding any sugar, we regarded the experiments of Pavy as entirely confirmed, and the fact demonstrated that the liver does not contain sugar during life. On the other hand, when we made the experiment on the liver as above described, and, in addition, took specimens of the portal blood and the blood from the hepatic veins, under strictly physiological conditions ( as was done in Experiment IY. ), and found no sugar in the portal blood or in the substance of the liver, but an abundance in the blood of the hepatic veins, it was impossible to avoid the conclusion that the sugar was formed in the liver, and was washed out in the blood as it passed through. In treating of the mechanism of the formation of sugar in the liver, we will describe more fully the glycogenic mat- ter ; but, taking into consideration the demonstration of the 1 Loc. cit. PRODUCTION OF SUGAR IN THE LIVER. 315 presence of sugar in the blood of the hepatic veins by Ber- nard ; his discovery of the post-mortem production of sugar in a liver washed sugar-free, probably from a substance re- maining in the liver and capable of being transformed into sugar ; the negative results of the examinations of the liver for sugar by Pavy ; and, adding to this our own experiments upon all of these points, we are justified in adopting the fol- lowing conclusions : 1. A substance exists in the healthy liver, which is capa- ble of being converted into sugar ; and inasmuch as this is formed into sugar during life, the sugar being washed away by the blood passing through the liver, it is perfectly proper to call it glycogenic, or sugar-forming matter. 2. The liver has a glycogenic function, which consists in the constant formation of sugar out of the glycogenic matter, this being carried away by the blood of the hepatic veins, which always contains sugar in a certain proportion. This production of sugar takes place in the carnivora, as well as in those animals that take sugar and starch as food ; and it is, essentially, independent of the kind of food taken. 3. During life, the liver contains only the glycogenic matter and no sugar, because the great mass of blood which is constantly passing through this organ washes out the sugar as fast as it is formed ; but after death, or when the circulation is interfered with, the transformation of glyco- genic matter into sugar goes on ; the sugar is not removed under these conditions, and can then be detected in the sub- stance of the liver. Characteristics of the Liver-Sugar. — Very little is to be said regarding the chemical peculiarities of liver-sugar. It resembles glucose, or the sugar resulting from the digestion of starch, in its composition, having for its formula, in a crystalline form, CiaHuO14. The formula for the anhydrous sugar is C12H12O12. This sugar, like glucose, responds promptly to all of the copper-tests, and undergoes trans- 316 SECRETION. formation into melassic acid on being boiled with an alkali. One of its most marked peculiarities is that it ferments more readily than any other variety of sugar ; and another pecu- liarity, described first by Bernard, is that it is destroyed in the economy with extraordinary facility. This fact has been illustrated by the following ingenious experiment : Bernard injected under the skin of a rabbit a little more than seven grains of cane-sugar, dissolved in about an ounce of water, and found sugar in the urine. Under the same conditions, he found he could inject seven grains of milk-sugar, fourteen and a half grains of glucose, twenty-one and a half grains of diabetic sugar, and nearly thirty grains of liver-sugar, without finding any sugar in the urine ; 1 showing that the liver-sugar is consumed in the organism more rapidly and completely than any other saccharine principle. Mechanism of the Production of Sugar in the Liver. — When Bernard first described the glycogenic function of the liver, he thought that the sugar was produced from nitro- genized principles, in some manner which he did not attempt to explain.8 Subsequent discoveries, however, have led to conclusions entirely different. In 1855, Bernard first published an account of his re- markable experiment showing the post-mortem production of sugar. After washing out the liver with water passed through the vessels, until it no longer contained a vestige of sugar, it was allowed to remain at about the temperature of the body for a few hours, and was then found to contain sugar in abundance.3 This experiment we have already re- ferred to, and it is one that we have frequently verified. Bernard explained the phenomenon by the supposition, sub- 1 BERNARD, Lemons de physiologic experimentale, Paris, 1855, p. 214. 2 BERNARD, Recherches sur une nouvelle fonction du foie, These, Paris, 1853, p. 77. 8 BERNARD, Sur h mecJianisme de la formation du sucre dans lefoie. — Comptes rendus, Paris, 1855, tome xli., p. 461. PRODUCTION OF SUGAR IK THE LIVER. 317 sequently shown to be correct, that the liver contains a peculiar principle, slightly soluble in water and capable of transformation into sugar. We have given rather a de- tailed account of this observation, because some authors have attributed the discovery of the glycogenic matter to Hensen. Hensen confirmed Bernard's observations, in 1856, and described the insoluble substance rather more fully.1 In 1857, Bernard studied the mechanism of the glycogenic function more closely, and completed his description of the glycogenic matter.3 Glycogenic Matter (C12HiaO12). — In its composition, re- actions, and particularly in the facility with which it under- goes transformation into sugar, glycogenic matter bears a very close resemblance to starch. It is described by Pavy under the name of amyloid matter,8 a name which is applied to it, also, by Rouget.4 It is insoluble in water, and, by vir- tue of this property, may be extracted from the liver after the sugar has been washed out. The following is the method for its extraction proposed by Bernard : 6 The liver of a small and young animal, like the rabbit, in full digestion, presents the most favorable conditions for the extraction of the glycogenic matter. The liver is taken from the animal immediately after it is killed, is cut into thin slices, and thrown into boiling water. When the tissue is hardened, it is removed and ground into a pulp in a mor- tar. It is then boiled a second time in the water of the 1 HENSEN, Ueber die Zucherbildung im thierischen Organismus. — SCHMIDT'S Jahrbuther, Leipzig, 1857, Bd. xciii., S. 15; taken from Verhandlungen derphy.- med. Gcs. zu, Wurzb., 1856, Bd. vii., S. 219. 2 BERNARD, Sur le mechanixme physiologique de la formation du sucre dans le foie. — Comptes rendus, Paris, 1857, tome xliv., p. 578. 3 PATY, Researches on the Nature and Treatment of Diabetes, London, 1862, p. 26, et seq. 4 ROUGET, Des substances amylo'ides ; de leur role dans la constitution dex tis- sus des animaux. — Journal de la physiologic, Paris, 1859, tome ii., pp. 83, 308. Rouget calls the glycogenic matter, or animal starch, zoamyline. 6 BERNARD, Liquides de Vorganisme, Paris, 1859, tome ii., p. 119. 318 •SECRETION. FIG. 12. E_J first decoction, strained through a cloth, and the opaline liquid which passes through is made into a thin paste with animal charcoal. The paste is then put into a dis- placement apparatus, the end of which is loosely filled with shreds of moistened cotton. By success- ive washings, the paste is ex- hausted of its glycogenic matter, leaving behind the albuminoid and coloring matters. The whit- ish liquid, as it flows, is received into a vessel of absolute alcohol, when, as each drop falls, the gly- cogenic matter is precipitated in great, white flakes. This is fil- tered and dried rapidly in a cur- rent of air. If the alcohol be M pn not allowed to become too dilute, the matter when dried is white and easily pulverized. The ap- paratus used by Bernard is repre- sented in Fig. 12 : A B, displace- ment apparatus in which the filtration takes place ; C, animal charcoal mixed with the decoction of the liver ; E, glycogenic solu- tion ; M, lamp-wicking, attached to a thread, passing through the carbon, and coming out at the upper part of the apparatus ; I, precipitating-glass ; G, glycogenic matter precipitated ; Y, alcohol.1 The substance thus obtained may "be held in suspension in water, giving to the liquid a strongly 2 BERNARD, op. dt., p. 120. PRODUCTION OF SUGAR IN THE LITER. 319 opaline appearance. It is neutral, without odor or taste, and presents nothing characteristic under the microscope. It reacts strongly with iodine, which produces a dark-violet or chestnut-brown color, but rarely a well-marked blue. It presents none of the reactions of sugar, and is entirely in- soluble in alcohol.1 It is changed into sugar by boiling for a long time with dilute acids, and this conversion is rapidly effected by the saliva, the pancreatic juice, and a- peculiar ferment found in the substance of the liver. Prepared in the way above indicated, and pulverized, it may be preserved for an indefinite period. The peculiar reaction of the glycogenic matter with iodine has led to its recognition in the substance of the liver- cells and in some other situations. Schiff found in the liver-cells minute granulations, which presented the peculiar color on the addition of iodine, characteristic of glycogenic matter.3 Bernard, a few years after his discovery of this principle in the liver, recognized it in cells attached to the placenta. He believes that these cells produce sugar during the early period of foetal life, before the liver takes on this function, and that they disappear during the later months, as the liver becomes fully developed.3 Since the discovery of the glycogenic function of the liver, anatomists have found amyloid corpuscles in various of the tissues of the body. We do not propose, however, to discuss this question in all its bearings, but only to consider the known relations of the amyloid substances found in the body to the formation of sugar. In the first place, there can be no doubt of the fact, that the liver of a carnivorous animal that has been fed exclu- sively on meat contains an amyloid substance readily con- 1 BERNARD, Lemons sur la physiologic et la pathologic dit systeme nerveux, Paris, 1858, tome i., p. 4tO. 2 SCHIFF, De la nature des granulations qui remplissent les cellules hepatiques : Amidon animak. — Comptes rendm, Paris, 1859, tome xlviii., p. 880. 3 BERNARD, Sur une nouvdle fonction du placenta. — Journal de la physiologic, Paris, 1859, tome ii., p. 31, et seq. 320 SECRETION. vertible into sugar. The experiments of Bernard, of Pavy, and all, indeed, agree upon this point. The question of the existence of the same amyloid matter in other tissues and organs is only pertinent in so far as it bears upon the pro- duction of sugar or upon the formation of the glycogenic matter in the liver. In no tissue or organ in the adult has it been demonstrated that there is any formation of sugar, except the ordinary transformation of starch into sugar in the process of digestion ; but it has been claimed that amy- loid matter is contained in the flesh of herbivorous animals, and is taken up by the carniv.ora and deposited in the liver. M. Sanson has made two elaborate communications on this subject, and concludes, from his own experiments, that the liver has no glycogenic function.1 These experiments were repeated by M. Sanson in the presence of a commission from the French Academy of Medicine, composed of MM. Bouley, Poggiale, and Longet, and were reported upon to the Acad- emy. The conclusions of the commission were unreservedly in favor of the glycogenic function of the liver ; and out of a great number of observations, in only one was any amyloid matter discovered in butcher's meat.3 It was found normally in horse-flesh, and, as subsequent experiments showed, could be produced in the muscular tissue of various of the her- bivora, by feeding them upon certain articles, particularly oats and barley.3 If the liver taken from an animal freshly killed be simply kept at about the temperature of the body, after it has been drained of blood, or even after it has been washed through the vessels, sugar will be rapidly formed in its substance. 1 SANSON, De Vorigine du sucre dans feconomie animate. — Journal de la physiologic, Paris, 1858, tome i., p. 244, et seq., and Sur Vexistence de la matiere glycogene dans tous les organes des herbivores et sur Vinfluence de V alimentation sur la production de cette substance. — Journal de la physiologic, Paris, 1859, tome ii., p. 104, et seq. 2 POGGIALE, Sur la formation de la matidre glycogene dans V economic animale.— Journal de la physiologic, Paris, 1858, tome i., p. 549, et seq. 3 BERNARD, Liquides de Vorganisme, Paris, 1859, tomeii., p. 111. PRODUCTION OF STJGAB IN THE LIVEK. 321 This must be due to some ferment remaining in the tissue ; and Bernard has, indeed, been able to isolate a principle which exerts this influence in a marked degree. If an opaline decoction of the liver be allowed to stand until it has become entirely clear, showing that all the glycogenic mat- ter has been transformed into sugar, and alcohol be added to the liquid, the hepatic ferment will be precipitated. This may be redissolved in water, and it effects the transforma- tion of starch into sugar with great rapidity.1 From these facts it is pretty conclusively shown that the following is the mechanism of the production of sugar in the liver : The liver first produces a peculiar principle, analogous to starch in its composition and in many of its properties, though it contains two atoms more of water, out of which the sugar is to be formed. The name, glycogenic matter, may properly be applied to this substance. It is, as far as is known, produced in all classes of animals, carnivora and herbivora ; and though its quantity may be modified by the kind of food, its formation is essentially independent of the alimentary principles absorbed. The glycogenic matter is not taken up by the blood as it passes through the liver, but is gradually transformed, in the substance of the liver, into sugar, which is washed out of the organ as fast as it is produced. Thus the blood of the hepatic veins always contains sugar, though sugar is not contained in the substance of the liver during life. Variations in the Glycogenic Function. In following out the relations of the glycogenic process to the various animal functions, Bernard studied very closely its variations at different periods of life, with digestion, the influence of the nervous system, and other modifying condi- tions. He made some of his observations by examining the 1 BERNARD, op. ezz., p. 124. 21 322 SECRETION. blood in living animals, and others, by estimating the pro- portion of sugar in the liver. The latter method must be considered, with an appreciation of the fact that the liver does not normally contain sugar during life ; but it repre- sents, to a certain extent, the activity of the glycogenic function. Still, the facts arrived at in this way must be taken with a certain degree of caution. Glycogenesis in the Foetus. — In. the early months of foetal existence, many of the tissues and fluids of the body were found by Bernard to be strongly saccharine ; but at this time no sugar is to be found in the liver. Taking the ob- servations upon foetal calves as the criterion, sugar does not appear in the liver until toward the fourth or fifth month of intra-uterine life.1 Before this period, however, epithelial cells filled with glycogenic matter are found in the placenta, and these produce sugar until the liver takes on its functions. As the result of numerous observations by Bernard upon foetal calves, this function of the placenta appears very early in foetal life, and, at the third or fourth month, has attained its maximum. At about this time, when glycogenic matter begins to appear in the liver, the glycogenic organs of the placenta become atrophied, and are lost some time before birth.8 Influence of Digestion, and of Different Kinds of Food. — Activity of the digestive organs has a marked influence upon the production of sugar in the liver. In a fasting ani- mal, sugar is always found in the blood of the hepatic veins and in the vessels between the liver and the heart, but it 1 BERNARD, Lemons de physiologic experimental^ Paris, 1855, p. 82. 2 BERNARD, Sur une nouvelle fonction du placenta. — Journal de la physiologie, Paris, 1859, tome ii., p. 33. Bernard found glycogenic matter in the placenta of animals in which the organ was single, as in the human subject ; but in ani- mals with multiple placenta he did not at first discover the glycogenic organs, which he subsequently found, not in the vascular portion, but attached to the amnion. PRODUCTION OF SUGAR IN THE LIVER. 323 never passes the lungs, and does not exist in the arterial system. During digestion, however, even when the diet is entirely nitrogenized, the production of sugar is so much increased that a small quantity frequently escapes decompo- sition in the lungs, and passes into the arterial blood.1 Un- der these conditions, the quantity in the arterial blood is sometimes so large that a trace may appear in the urine, as a temporary and exceptional, but not an abnormal condition. This physiological fact is well illustrated in certain cases of diabetes. There are instances, indeed, in which the sugar appears in the urine only during digestion ; a and in almost all cases, the quantity of sugar eliminated is largely increased after eating. Pavy mentions a very striking instance of this kind, in which the examinations of the urine were made with great care.8 The influence of the kind of food upon the glycogenie function is a question of great pathological as well as physi- ological importance. It is well known to pathologists that certain cases of diabetes are relieved when the patient is confined strictly to a diet containing neither saccharine nor amylaceous principles,* and that, almost always, the quantity of sugar discharged is very much diminished by such a course of treatment ; but there are instances in which the discharge of sugar continues, in spite of the most carefully-regulated diet. Bernard does not recognize fully the influence of dif- ferent kinds of food upon glycogenesis, and his experiments on this point are wanting in accuracy, from the fact that the proportion of sugar in the liver is given, without indicating at what period after death the examinations were made. In the observations on this point by Pavy, the examinations of 1 BERNARD, Lefons de physiologic experimentale, Paris, 1855, p. 111. 2 BERNARD, op. tit., p. 114. 3 PAVY, Researches on the Nature and Treatment of Diabetes, London, 1862, p. 142. 4 Several very striking examples of this kind are given by Pavy (op. «*., p. 107). 324 SECRETION. the liver were made immediately after death, and the pro- portion of glycogenic matter, not sugar, was estimated. His results are, consequently, much more reliable and satisfac- tory. In a number of analyses of the livers of dogs confined to different articles of diet, Pavy found a little over seven per cent, of glycogenic matter, upon a diet of animal food ; over seventeen per cent., upon a diet of vegetable food; and fourteen and a half per cent., upon a diet of animal food and sugar.1 These results have been confirmed by M'Donnell, who, in addition, found that hardly a trace of amyloid sub- stance could be detected in the liver on a diet of fat, and none whatever upon a diet of gelatine.2 Bernard had al- ready observed that the amount of sugar produced by the liver on a diet of fat was the same as during total abstinence from food.3 These facts are entirely in accordance with ob- servations upon the effects of different kinds of food in dia- betes, and they have an important bearing upon the dietetic measures to be employed in this disease. The effect of entire deprivation of food is to arrest the production of sugar in the liver, three or four days before death.4 This arrest of the glycogenic function has generally been observed in cases of disease, except when death has occurred suddenly. Influence of the Nervous System, etc. — Bernard has studied the influence of the nervous system upon the pro- duction of sugar more satisfactorily than any other of the variations of the glycogenic function, for the reason that he has noted these modifications by determining the sugar in the blood and the urine. Some of the points with regard to the nervous system we will consider again in another vol- ume ; and it is sufficient, in this connection, to mention the 1 PAVY, op. cit., p. 33, el seq. 8 M'DONNELL, Observations on the Functions of the Liver, Dublin, 1865, p. 14. 3 BERNARD, Lemons de physiologic experimentale, Paris, 1855, p. 137. * BERNARD, op. cit., p. 129. PRODUCTION OF SUGAR LIST THE LIVER. 325 main results of some of the most striking of the experiments on this subject. The most remarkable experiment upon the influence of the nervous system on the liver is the one in which artificial diabetes is produced by irritation of the floor of the fourth ventricle. This operation is not diffi- cult, and is one that we have often repeated. The instrument used is a delicate stilet, with a flat cutting extremity, and a small project- ing point, about -£% of an inch long.1 In per- forming the operation upon a rabbit, the head of the animal is firmly held in the left hand, and the skull is penetrated in the median line, just behind the superior occipi- tal protuberance. This can easily be done by a few lateral movements of the instrument. Once within the cranium, the instrument is passed obliquely downward and forward, so as to cross an imaginary line between the two auditory canals, until its point reaches the basilar process of the occipital bone. The point then penetrates the medulla oblongata, between the roots of the auditory nerves and the pneumogastrics, and, by its projection, serves to protect the nervous centre from more serious injury from the cutting edge. The instrument is then carefully withdrawn, -, . •• .. . i ,L i a mi • Instrument for pnnc- and the operation is completed. This ex- turin? the floor of . . , . -. -. . . . , , the fourth ventricle penment is almost painless, and it is not de- (BERNARD, Leyons , , , . . ,, , . de physiologie ex- sirable to administer an anaesthetic, as this, pfrtmaOate^ Pan?, 1855, p. 290). in itself, would disturb the glycogenic pro- cess. The urine may be drawn before the operation, by pressing the lower part of the abdomen, taking care not to 1 These instruments have been made by Messrs. Tiemann & Co., of this city. 2 BERNARD, Lemons de physiologic experimentale, Paris, 1855, p. 291, et seq. 326 SECRETION. allow the bladder to pass up above the point of pressure, and it will be found turbid, alkaline, and without sugar. In one or two hours after the operation, the urine will have be- come clear, acid, and will react readily with any of the copper-tests. "When this operation is performed without in- juring the adjacent organs, the presence of sugar in the urine is only temporary, and the next day, the secretion FIG. 14. Section of the head of a rabbit, showing the operation of puncturing the floor of the fourth ventricle, a, cerebellum ; J, origin of the seventh pair of nerves ; c, spinal cord ; d, origin of the pneumogastric ; e, opening of entrance of the instrument into the cranium : /, instrument ; g, fifth pair of nerves ; A, auditory canal ; i, extremity of the instrument on the spinal cord after having penetrated the cerebellum ; #, oc- cipital venous sinus ; /, tubercula quadrigemina ; m, cerebrum ; n, section of the atlas. — (BERNARD, Lemons de physiologic experimental, Paris, 1855, p. 293.) will have returned to its normal condition. It is best, in performing this experiment, to operate on an animal in full digestion, when the production of sugar is at its maximum. The production of diabetes in this way, in animals, is exceedingly interesting in its relations to certain cases of the disease in the human subject, in which the affection is trau- matic, and directly attributable to injury near the medulla. PRODUCTION OF SUGAR IN THE LIVER. 327 Its mechanism it is difficult to explain. The irritation is not propagated through the pneumogastric nerves, for the experiment succeeds after both of these nerves have been divided ; 1 but the influence of the pneumogastrics upon gljcogenesis is curious and interesting. If both of these nerves be divided in the neck, in a few hours or days, de- pending upon the length of time that the animal survives the operation, no sugar is to be found in the liver, and there is reason to believe that the glycogenic function is arrested. After division of the nerves in this situation, galvanization of their peripheral ends does not affect the production of sugar; but, by galvanization of the central ends, an impres- sion is conveyed to the nervous centre, which is reflected to the liver, and produces a hypersecretion of sugar.3 These questions will be referred to again, in connection with the physiology of the nervous system. With regard to the influence of the sympathetic system upon the glycogenic function, there have been few experi- ments which lead to conclusions of any great value. Pavy found that division of the sympathetic filaments accompany- ing the vertebral arteries produced diabetes, but the opera- tion was complicated by lesions of the vessels, which ren- dered the results somewhat unsatisfactory.8 It has been observed that the inhalation of anaesthetics and irritating vapors produces temporary diabetes;4 and this has been attributed to the irritation conveyed by the pneumogastrics to the nerve-centre, and reflected, in the form of a stimulus, to the liver. It is for this reason that we should avoid the administration of anaesthetics in all ac- curate experiments on the glycogenic function. In illustra- tion of this fact, Pavy has collected twenty cases, in which 1 BERNARD, loc. cit., p. 317. 3 BERNARD, op. cz7., p. 324. It has been observed by Bernard that division of the pneumogastrics in the chest, between the lungs and the liver, does not affect the production of sugar (p. 328). 3 PATY, op. tit., p. 87, et seq. 4 BERNARD, op. oil., p. 327. 328 SECRETION. chloroform was administered in the human subject for surgi- cal operations, in all of which the passage of a small quan- tity of sugar in the urine was noted.1 Destination of Sugar. — Although sugar is constantly produced by the liver and taken up by the circulation, it is ex- ceptional to find it in the blood after it has passed through the lungs. It is difficult to ascertain the precise mode of its destruction in the lungs, and, indeed, the nutritive function of sugar in the economy is not thoroughly understood. All that we can say of the destination of liver-sugar is, that it probably has the same office in nutrition as the sugar taken as food and that resulting from the digestion of amylaceous matters. The facts bearing upon this question will be re- viewed under the head of nutrition. Alleged Production of Fat Tyy the Liver. — It is stated by Bernard, that in animals fed largely with saccharine and amylaceous principles, the blood of the hepatic veins con- tains an emulsive matter, which seems to be fat combined with a proteine substance. In support of the opinion that fat is thus produced in the liver, he brings forward that well- known fact, that a diet of starch and sugar is particularly favorable to the development of adipose tissue.3 But the examinations of the matter supposed to be fatty have not been sufficiently minute to lead to any positive conclusions with regard to its character or composition. Rouget states, unreservedly, that this substance is simply glycogenic or amyloid matter.3 "While there can be no doubt of the forma- tion of fat in the organism independently of the fat taken as food, there is not sufficient ground for regarding the liver as one of the organs specially concerned in its production. 1 Op. tit., p. so. 2 BERNARD, Legons de physiologic cxperimentale, Paris, 1855, p. 154. 8 ROUGET, Des substances amyloides. — Journal de la physiologic, Paris, 1859, tome ii., p. 324. CHANGES IN THE BLOOD IN THE LTVEB, 329 Changes in the Albuminoid and the Corpuscular Ele- ments of the Blood in passing through the Liver. — In verify- ing the observations of Bernard upon the presence of sugar in the blood of the hepatic veins, Lehinann was led to observe other differences in the composition of the blood from these vessels, as compared with the portal blood and the blood of the arterial system. One of the most important of these was the absence of fibrin. While the portal blood co- agulates strongly, like blood from any other part of the body, the^ blood of the hepatic veins does not coagulate, and " the fibrin is either entirely absent, or is present in mere traces." * This observation has been confirmed by Brown-Sequard,8 and, later, by M'Donnell, who describes a peculiar caseous matter as existing specially in the blood of the hepatic veins.3 Lehmann also noted that the proportion of serum to corpuscles was much less in the hepatic than in the por- tal blood. The serum from the hepatic veins was found to present a diminution in albumen, amounting to fully one- third. Some very curious observations were also made by Leh- mann upon the blood-corpuscles in the hepatic vessels. He estimated that the proportion of white corpuscles in the blood of the hepatic veins was at least fivefold the propor- tion in the portal blood. He also noted certain differences in the appearance of the red corpuscles, which he explained by the supposition that the liver was the seat of development of these elements, which were formed from the white cor- puscles, and that the blood of the hepatic veins contained a 1 LEHMAXN, Physiological Chemistry, Philadelphia, 1855, TO!, i., p. 489. Sev- eral years before, Simon observed that fibrin was separated with difficulty from the blood of the hepatic veins, and was not to be found in the blood of the renal veins (SiMON, Animal Chemistry, Philadelphia, 1846, pp. 174, 178). 2 BROWN-SEQUARD, Sur des faits qui semblent montrer que plusieurs kilo- grammes de fibrine se forment et se transformer^, chaque jour dans le corps de Vhomme, — Journal de la physiologie, Paris, 1858, tome i., p. 300. 3 M'DONNELL, Observations on the Functions of the Liver, Dublin, 1865, p. 34. 330 SECRETION. greater number of "newly-formed or rejuvenescent blood- corpuscles." It is not our purpose, in this connection, to discuss the development of the corpuscular elements of the blood ; but it is interesting to note the above-mentioned changes in the blood as it passes through the liver. The physiological sig- nificance of the destruction of fibrin and albumen is not un- derstood, although the fact is undoubted. 1 Op. tit., pp. 498, 499. CHAPTER XI. THE DUCTLESS GLANDS. Probable office of the ductless glands — Anatomy of the spleen— Fibrous struc- ture of the spleen (trabeculse) — Malpighian bodies — Spleen-pulp — Vessels and nerves of the spleen — Some points in the chemical constitution of the spleen — State of our knowledge concerning the functions of the spleen — Variations in the volume of the spleen during life — Extirpation of the spleen — Anatomy of the suprarenal capsules — Cortical substance — Medul- lary substance — Vessels and nerves — Chemical reactions of the suprarenal capsules — State of our knowledge concerning the functions of the supra- renal capsules — Extirpation of the suprarenal capsules — Addison's disease — Anatomy of the thyroid gland — State of our knowledge concerning the functions of the thyroid gland — Anatomy of the thymus — Pituitary body and pineal gland. CERTAIN organs in the body, with a structure resem- bling, in some regards, the true glands, but without excre- tory ducts, have long been the subject of physiological spec- ulation ; and the most extravagant notions concerning their functions have prevailed in the early history of the science. The discovery of those functions of the liver which consist in modifications in the composition of the blood dimly indicated the probable office of the ductless glands ; for, as far as the production of sugar is concerned, the liver belongs to this class. Indeed, the supposition that the ductless glands effect some change in the blood is now regarded by physiol- ogists as the most reasonable of the many theories that have been entertained concerning their office in the economy; and this view is adopted by those, even, who do not admit the existence of a glycogenic function in the liver. Under 332 SECRETION. this idea, these organs have been called blood-glands, or vas- cular glands; but inasmuch as the supposition that these parts effect changes in the blood or lymph is merely to sup- ply the want of any definite idea of their function, and rests mainly upon analogy with certain of the functions of the liver, we shall retain the name, ductless glands, as indicating the most striking of their anatomical peculiarities. As far as presenting any definite and important physio- logical information is concerned, we might terminate here the history of the ductless glands. It is true that the largest of them, the spleen, has been extensively experi- mented upon by the earlier physiologists ; but in point of fact, investigations have done little more than exhibit a want of knowledge of the functions of these remarkable organs ; and the literature of the subject is mainly a collection of wild speculations and fruitless experiments. There are, however, some interesting experimental facts with relation to the spleen and the suprarenal capsules ; though they are not very instructive, except that they indicate the extremely narrow limits of our positive knowledge. These few facts, with a sketch of the anatomy of the parts, will embrace all that we shall have to say concerning the ductless glands. Under this head are classed, the spleen, suprarenal capsules, thyroid gland, thymus, and sometimes the pituitary body and the pineal gland. These parts have certain anatomical points in common with each other, but on account of our want of knowledge of their functions, it is difficult to distin- guish, as we have done in other organs, their physiological anatomy. Anatomy of the Spleen. The spleen is found, with but few exceptions, in all ver- tebrate animals, but does not exist in the invertebrata.1 It 1 This organ, according to Van der Hoeven, is not found in the cyclostomes and the lepidosiren (Handbook of Zoology, Cambridge, 1858, vol. ii., p. 29); and Milne-Edwards states that it is absent also in the amphioxus (Lemons sur la DUCTLESS GLANDS. 333 is situated in the left hypochondriac region, next the cardiac extremity of the stomach. Its color is of a dark bluish-red, and its consistence is rather soft and friable. It is shaped somewhat like the tongue of a dog, presenting above, a rather thickened extremity, which is in relation with the diaphragm, and below, a pointed extremity, in relation with the transverse colon. Its external surface is convex, and its internal surface concave, presenting a vertical fissure, the hilum, giving passage to the vessels and nerves. It is con- nected with the stomach by the gastro-splenic omentum, and is still further fixed by a fold of the peritoneum passing to the diaphragm. It is about five inches in length, three or four inches in breadth, and a little more than an inch in thickness. Its weight is between six and seven ounces. In the adult it attains its maximum of development, and diminishes slightly in size and weight in old age. In early life it bears about the same relation to the weight of the body as in the adult.1 It is frequently hypertrophied to an enormous extent in disease, weighing sometimes as much as twenty pounds.3 The external coat of the spleen is the peritoneum ; which is very closely adherent to the subjacent fibrous struc- ture. The proper coat is dense and resisting; but in the human subject is quite thin and somewhat translucent. It is composed of inelastic fibrous tissue, mixed with numerous small fibres of elastic tissue and a few unstriped muscular fibres. At the hilum the fibrous coat penetrates the substance of the spleen in the form of sheaths for the vessels and nerves ; an arrangement entirely analogous to the fibrous physiologic, Paris, 1862, tome vii., p. 235). According to Gray, the spleen exists without exception in all the vertebrate animals ( Structure and Use of the Spleen, London, 1854, p. 272). 1 Mr. Gray, in his elaborate essay on the spleen, gives a very extended table of the weight of this organ at different periods of life (Structure and Use of the Spleen, London, 1854, p. 76). 8 GRAY, Anatomy, Descriptive and Surgical, Philadelphia, 1862, p. 685. 334 SECRETION. sheath in the liver. The number of the sheaths in the spleen is equal to the number of arteries that penetrate the organ. This is sometimes called the capsule of Malpighi.1 The fibrous sheaths are closely adherent to the surrounding substance, but are united to .the vessels by a loose fibrous net-work. They follow the vessels in their ramifications to the smallest branches, and are lost in the spleen-pulp. Be- tween the sheath and the outer coat, are numerous bands or trabeculse of the same structure as the fibrous coat. The presence of elastic fibres in these structures can be easily demonstrated, and this kind of tissue is very abundant in the herbivora. In the carnivora the muscular tissue is par- ticularly abundant, and can be readily demonstrated ; 2 but in man this is not so easy, and the fibres are less numerous. There can be no doubt, however, that muscular tissue exists in the human subject throughout the whole extent of the fibrous structure, and the fibres are demonstrated without much difficulty in the trabeculse.3 These peculiarities in the fibrous structure are important in their relation to certain physiological changes in the size of the spleen. Its contractility can be easily demonstrated in the dog by the application of a galvanic current to the nerves as they enter at the hilum. This is followed by a prompt and energetic contraction of the organ. Contrac- tions may be produced, though they are much more feeble, by applying the current directly to the spleen.4 The substance of the spleen is soft and friable ; and a portion of it, the spleen-pulp, may be easily pressed out, or even washed away by a current of water. Aside from the vessels and nerves, it presents for study : 1. An arrange- 1 MALPIGHI, De Liene, Opera Omnia, Lugd. Batav., 1687, tomus ii., p. 294. 2 Kolliker has demonstrated the presence of muscular fibres in considerable numbers in the dog, pig, ass, and cat ; but they were not discovered in the rab- bit, horse, ox, hedgehog, porpoise, or bat (Handbuch dcr Gewebelchre, Leipzig, 1867, S. 449). 3 SAPPEY, Traite d'anaiomie, Paris, 1857, tome iii., p. 323. 4 BERNARD, Lefons sur les liquides deVorganisme, Paris, 1859, tome ii., p. 421. DUCTLESS GLANDS. 335 ment of fibrous bands, or trabeculae, by which it is divided into innumerable communicating cellular interspaces. 2. Closed vesicles ( Malpighian bodies), attached to the walls of the blood-vessels. 3. A soft, reddish substance, contain- ing numerous cells and free nuclei, called the spleen-pulp. Fibrous Structure of the Spleen (Trabeculce). — From the internal face of the investing membrane of the spleen, and from the fibrous sheath of the vessels (capsule of Malpighi) are numerous bands, or trabeculse, which, by their inter- lacement, divide the substance of the organ into irregularly- shaped, communicating cavities. These bands are from -^ to -^ of an inch broad, and are composed, like the proper coat, of ordinary fibrous tissue with elastic fibres and a few smooth muscular fibres. They pass off from the capsule of Malpighi and the fibrous coat at right angles, very soon branch, interlace, and unite with each other, becoming smaller and smaller, until they measure from -g-J-g- to -fa of an inch.1 The smaller bands are cylindrical, and it is in these that the muscular tissue can be demonstrated with the greatest facility. As we should expect from the very variable size of the trabeculae, the dimensions as well as the form of the cavities are exceedingly irregular. This fibrous net-work serves as a skeleton or a support for the softer and more delicate parts. Malpighian Bodies. — In the very elaborate work on the spleen, by Malpighi, is a full account of the closed follicles, which have since been called the Malpighian bodies.3 They are sometimes called the splenic corpuscles or glands. They are in the form of rounded or slightly ovoid corpuscles, about -^j- of an inch in diameter, consisting of a delicate membrane, generally homogeneous, but sometimes faintly striated, with semifluid contents. In their form, size, and structure, they 1 SAPPET, Traite cTanatomie, Paris, 1857, tome iii., p. 323. 8 MALPIGHI, De Liene, Opera Omnia, Lugd. Batav., 1687, tomus ii., p. 300. 336 SECRETION. bear a close resemblance to the closed follicles of tlie small intestine.1 The investing membrane has no epithelial lining, and the contents consist of an albuminoid liquid, with numer- ous small, nucleated cells, and a few free nuclei. The cells measure from -g-^ViF to -g-gVir of an inch in diameter. Both the cells and the free nuclei of the splenic corpuscles bear a close resemblance to cells and nuclei found in the spleen- pulp. The corpuscles are surrounded by blood-vessels, which send branches into the interior to form a delicate capillary plexus.3 The number of the Malpighian corpuscles in a spleen of ordinary size has been estimated by Sappey at from seven thousand to eight thousand.3 They are readily made out in the ox and sheep, but are frequently not to be discovered in the human subject. In about forty examinations, in man, Sappey found them in only four ; but in these they presented the same characters as in the ox and the sheep, and resisted decomposition for twelve days,4 showing that it is not neces- sary to have recourse to perfectly fresh specimens to dis- cover them if they exist. Kolliker notes the fact that they are often absent in the human subject when death has taken place from disease or long abstinence. He believes that they are nearly always to be found in perfectly healthy per- sons.6 The occasional absence of these bodies constitutes another point of resemblance to the solitary glands of the small intestine.8 The relations of the Malpighian bodies to the arterial branches distributed through 'the spleen are peculiar. In specimens in which these corpuscles are easily made out, if a thin section be made, and the spleen-pulp be washed away by a stream of water, the corpuscles may be seen attached in some parts to the sides of the vessels, in others lying in 1 See vol. ii., Digestion, p. 321. 2 KOLLIKER, Handbuch der Gewebelehre, Leipzig, 1867, S. 456. 3 SAPPEY, op. cit., p. 326. 4 Idem., p. 325. 6 KOLLIKER, op. cit., S. 454. 6 See vol. ii., Digestion, p. 319. DUCTLESS GLANDS. 337 the notch formed by the branching of a vessel, and in others attached to an extremity of an arterial twig, the vessel then breaking up into a plexus to surround the corpuscle. Ac- cording to Sappey, the corpuscles are attached to arteries measuring from -g^ to -^ of an inch or less in diameter.1 When the artery is enclosed in its fibrous sheath, the corpus- cles are applied to the sheath, but in the smallest arteries they are attached to the walls of the vessel. The attach- ment of the Malpighian bodies to the vessels is very firm, and they cannot be separated without laceration of the membrane. Spleen-pulp. — "With, regard to the constitution of the spleen-pulp, there is considerable diversity of opinion. While anatomists and physiologists are pretty generally agreed concerning the structure and relations of the Mal- pighian bodies, some minutely describe cells in the pulp, the existence of which is denied by others of equal authority. The pulp, however, contains the essential elements of the spleen, and an accurate knowledge of all the structures con- tained in it could hardly fail to throw some light on its func- tion ; but there is so little that is definitely known of either the anatomy or the physiology of the spleen, that we shall refrain from discussing the views of different authors, refer- ring the reader for full information upon these points to the elaborate works upon general anatomy. The pulp is a dark, reddish, semifluid substance, its color varying in intensity in different specimens. It is so soft that it may be washed by a stream of water from -a thin section, and it readily decomposes, becoming then nearly fluid. It is contained in the cavities bounded by the fibrous trabeculae, and itself contains numerous microscopic bands of fibres arranged in the same way. It surrounds the Malpighian bodies, contains the terminal branches of the blood-vessels, and probably the nerves and lymphatics. Upon microscopi- 1 Op. tit., p. 328. 22 338 SECRETION. cal examination, it presents numerous free nuclei and cells, like those described in the Malpighian bodies ; but the nuclei are here relatively much more abundant. In addition are found, blood-corpuscles, white and red, some natural in form and size, others more or less altered, with pigmentary granules, both free and enclosed in cells. Anatomists have attached a great deal of importance to large vesicles en- closing what have been supposed by some to be blood-cor- puscles, and by others to be pigmentary corpuscles. The state of our knowledge on these points, however, is very unsatisfactory. Some authorities deny the existence of the so-called blood-corpuscle-containing cells. A writer in the British and Foreign Medico- Chirurgical JReview, in 1853, after a thorough analysis of the various original observations that had appeared up to that time, came to the conclusion that the presence in the spleen-pulp of cells containing blood- corpuscles in a transition state was extremely doubtful ; 1 and Kolliker, who has investigated the structure of the spleen with peculiar care, has advanced, in successive publications, several entirely different opinions on the subject.3 "We will therefore abstain from a discussion of these disputed ques- tions, which are at present of a character purely anatomical. All that we can say of the spleen-pulp is, that it contains cells, nuclei, blood-corpuscles, and pigmentary granules, with a yellowish-red fluid ; and that it is intersected with micro- scopic trabeculse of fibrous and muscular tissue, and a deli- cate net-work of blood-vessels. It is difficult to determine whether the blood-corpuscles come from vessels that have been divided in making the preparation, or are really free in the pulp ; or whether the free nuclei are normal or come from cells that have been artificially ruptured. 1 WHARTON JONES, British and Foreign Medico- Chirurgical Review, London, 1853, vol. xi., p. 32. 2 KOLLIKER, Cyclopaedia of Anatomy and Physiology, London, 1847-1849, vol. iv., p. 771, Article, Spleen. Manual of Human Microscopic Anatomy, London, 1860, p. 358, et seg. Handbuch der Gewebelehre des MenscJien, Leipzig, 1867, S. 448, et seq. DUCTLESS GLANDS. 339 Vessels and Nerves of the Spleen. — The quantity of blood which the spleen receives is very large in proportion to the size of the organ. The splenic artery is the largest branch of the coeliac axis. It is a vessel of considerable length, and is remarkable for its excessively tortuous course. In a man of between forty and fifty years of age, the vessel measured about five inches, without taking account of its deflections ; and a thread placed on the vessel, so as to follow exactly all its windings, measured a little more than eight inches.1 The large calibre of this vessel and its tortuous course are interesting points in connection with the great variations in size and situation which the spleen is liable to undergo in health and disease. The artery gives off several branches to the adjacent viscera in its course, and as it passes to the hilum divides into three or four branches, which again divide so as to form from six to ten vessels. These penetrate the substance of the spleen, with the veins, nerves, and lymphatics, enveloped in the fibrous sheath, the capsule of Malpighi. In the substance of the spleen the arteries branch rather peculiarly, giving off many small ramifica- tions in their course, generally at right angles to the parent trunk. These are accompanied by the veins until they are reduced to from -^j- to -fa of an inch in diameter. The two classes of vessels then separate, and the arteries have at- tached to them the corpuscles of Malpighi. It is also a noticeable fact that the distinct trunks passing in at the hilum have but few inosculations with each other in the substance of the spleen, so that the organ is divided up into from six to ten vascular compartments. This arrangement was observed many years ago by Assollant.3 The veins join the fine branches of the arteries in the spleen-pulp and pass out of the spleen in the same sheath. They anastomose quite freely in their larger as well as their 1 SAPPEY, Tratie cTanatomie, Paris, 1857, tome iii., p. 327. 2 ASSOLLAXT, Recherche* sur la rate.— These, No. 112, Paris, an xii. (1804), p. 36. 340 SECKETION. smaller branches. Their calibre is estimated by Sappey as about twice that of the arteries. This author regards the estimates, that have put the calibre of the veins at four or five times that of the arteries, as much exaggerated.1 The number of veins emerging from the spleen is equal to the number of arteries of supply. The lymphatics of the spleen are not numerous. By most anatomists, two sets of vessels have been recognized, the superficial and the deep; but those who have studied the subject practically have found it very difficult to demon- strate the superficial layer. Sappey denies the existence of any but the deep vessels;2 and Kolliker admits that the superficial vessels are generally not to be found in morbid spleens, and are very scanty in perfectly healthy specimens.3 The deep lymphatics have been demonstrated in the capsule of Malpighi, attached to the veins and emerging with them at the hilum. At the hilum, according to Kolliker, the deep vessels are joined by a few from the surface of the spleen. The vessels, numbering five or six, then pass into small lymphatic glands, and empty into the thoracic duct opposite the eleventh or twelfth dorsal vertebra. It was an old idea that the lymphatics were the excretory ducts of the spleen.4 This view was revived by Hewson,6 but it is a speculation which does not demand any discussion at the present day. The nerves of the spleen are derived from the solar plexus. They follow the vessels in their distribution, and are enclosed with them in the capsule of Malpighi. They 1 Op. cii., p. 329. 2 SAPPEY, Traite tfanatomie, Paris, 1857, tome iii., p. 331. 3 KOLLIKER, Handbuch dcr Gewebelehre, Leipzig, 1867, S. 460. 4 In Milne-Edwards's elaborate work on physiology, now in course of publi- cation, is an exhaustive bibliographical review of the early works on the anato- my and physiology of the spleen. The idea that the lymphatics were its ex- cretory ducts was advanced by Eller, in 1716. (MILNE-EDWARDS, Lemons sur la physiologic, Paris, 1862, tome vii., p. 233, et seq.) 6 HEWSON, Works, Sydcnham Society Publication, London, 1846, p. 271. DUCTLESS GLANDS. 341 are distributed ultimately in the spleen-pulp, but nothing definite is known of their mode of termination. "We have already referred to the fact that when these nerves are gal- vanized, the non-striated muscles in the substance of the spleen are thrown into contraction. Some Points in the Chemical Constitution of the Spleen. —Very little has been learned with regard to the .probable function of the spleen, from the numerous chemical analyses that have been made of its substance. It will therefore be out of place to discuss its chemical constitution very fully, and we will only refer to certain principles, the existence of which, in the spleen-substance, may be considered as pretty well determined. In the first place, cholesterine has been found to exist in the spleen constantly and in considerable quantity, and the same may be said of uric acid. In addi- tion, chemists have extracted from the substance of the spleen, hypoxanthine, leucine, tyrosine, a peculiar crystal- lizable substance called, by Scherer, lienine, crystals of hsematoidine, lactic acid, acetic acid, butyric acid, inosite, amyloid matter, and some indefinite fatty principles.1 It is difficult, however, to say how far some of these principles are formed by the processes employed for their extraction, or are due to morbid action; certainly, physiologists have thus far been unable to connect them with any definite views of the probable function of the spleen. State of our Knowledge concerning the Functions of the Spleen. — The spleen is almost universal in vertebrate ani- mals ; it is an organ of considerable size, and is very abun- dantly supplied with vessels and nerves ; it has a complex structure, unlike that of any of the true glands ; its tissue presents a variety of proximate principles ; but it has no ex- cretory duct, and no opportunity is afforded for the study of its secretion, except as it may be taken up by the current 1 MILSE-EDWARDS, Lemons sur la physiologic, Paris, 1862, tome vii., p. 259. 342 SECRETION. of blood. It must be admitted, also, that up to the present time, no definite physiological ideas have followed the elabo- rate microscopical and chemical examinations of the spleen. There have been only two methods of inquiry, indeed, which have promised any such results : First, a comparison of the blood and lymph going into and coming from the spleen, and an examination of the variations in the volume of the organ during life ; and second, a study of the phenomena which follow its extirpation in living animals. A review of the literature of the subject will show that we have gained but little positive information from either of these methods. The condition of the question of the influence of the spleen upon the composition of the blood is well illustrated in the last edition of Longet's elaborate work on physiol- ogy.1 This author quotes opinions of the highest authori- ties, based chiefly upon microscopical investigations, some in favor of the view that the blood-coi*puscles are destroyed, and others arguing that they are formed in the spleen, while he himself oifers no opinion upon the subject. Still there are certain established points of difference between the blood of the splenic artery and of the splenic vein. There can be no doubt of the fact that the blood coming from the spleen contains a large excess of white cor- puscles. Donne was the first to call attention to this fact,2 and his observations have been confirmed by Gray,3 and many others.4 It can by no means be considered settled, however, that the function of the spleen is to form white blood-corpuscles. In pathology, although great increase in the leucocytes of the blood frequently attends hypertrophy 1 LONGET, Traite de physiologic, Paris, 1869, p. 378. • DONNE, Cours de microscopic, Paris, 1844, p. 99. Donne states that the blood taken from the splenic veins presents nothing remarkable ; but on press- ing out that contained in the tissue of the organ, the white corpuscles were very abundant, and were even more numerous than the red. 3 GRAY, The Structure and Use of the Spleen, London, 1854, p. 150. 4 MILNE-EDWARDS, Lecons sur la physiologie, Paris, 185Y, tome i., p. 352, and 1862, tome vii., p. 256. DUCTLESS GLANDS. 343 of the spleen, this condition is also observed when the spleen is perfectly healthy. Diminution in the proportion of red corpuscles in the blood in passing through the spleen, in a very marked degree, has been noted by Beclard,1 Gray,8 and others, and this gives color to the supposition that the spleen is an organ for the destruction of the blood-corpuscles ; but we know nothing of the importance or significance of this process, and it is not shown that the corpuscles exist in undue quantity in ani- mals after the spleen has been removed. We learn nothing more definite from, the fact that blood of the splenic vein seems to contain an unusual quantity of pigmentary matter.3 In connection with the marked diminution in the proportion of blood-corpuscles, both Beclard 4 and Gray 6 observed a marked increase in the fibrin and albumen in the blood of the splenic vein. The significance of the facts just stated is so little under- stood, that it would seem hardly necessary even to mention them, except as an illustration of the small amount of defi- nite information regarding the functions of the spleen that has resulted from an examination of the blood coming from this organ. We know nothing of any changes effected by the spleen in the constitution of the lymph. Variations in the Volume of the Spleen during Life. — One of the theories with regard to the function of the spleen, which merits a certain amount of consideration, is that it serves as a diverticulum for the blood, when there is a ten- dency to congestion of the other abdominal viscera. The first attempt to formularize this idea and support it by ex- perimental observations was made by Dobson, in 1830. He noted the fact that the spleen was much larger in dogs, from 1 BECLARD, Recherches experimentales sur les fonctions de la rate et sur celles de la veine porte. — Archives generates de medecine, Paris, 1848, 4me serie, tome xviii., pp. 143, 442. 2 GRAY, op. tit., p. 156. 3 Idem., p. 147. 4 BECLARD, loc. tit., p. 443. 5 GRAY, loc. tit., p. 152. 344 SECEETION. four to five hours after eating, than during the intervals of digestion ; and he formally advanced the opinion that the spleen serves as a diverticulum for the blood during the pe- riod when there is a great afflux to the digestive organs, and that the extent of its enlargement is in direct ratio to the amount taken into the stomach.1 Of the accuracy of these experiments there can be no doubt ; " but the second series of observations, in which Dobson attempted to show that large quantities of food cannot be taken with impunity by animals after the spleen has been extirpated, have not been so satisfactorily verified. "We have often removed the spleen from dogs, the operation being followed by complete recov- ery, and have never noted any thing unusual after feeding the animals very largely. In one observation, an animal from which the spleen had been removed six weeks before ate at one time a little more than four pounds of beef-heart, nearly one-fifth of his weight (the dog weighing twenty-two pounds), without suffering the slightest inconvenience. Dobson certainly established the fact that the spleen is greatly enlarged in dogs, from four to five hours after feed- ing, that its enlargement is at its maximum at about the fifth hour, and that it gradually diminishes to its original size during the succeeding twelve hours ; but it is not apparent how far this is important or essential to the proper perform- 1 DOBSON, Structure et fonctions de la rate. — Archives generales de medecine, Paris, 1830, tome xxiv., p. 431, et seq. The experiments and conclusions of Dobson are here quoted in full from the original memoir. Gray, who gives in his work upon the spleen a very full resume of the various theories with regard to the functions of the spleen, quotes (page 23) a Gulstonian lecture by Stuke- ley, in 1722, in which the same idea is advanced, though it eeems to be put forward merely as a theory, without any attempt at experimental proof. Hodgkin revived this opinion in 1822, but without presenting any positive proof of its accuracy (HODGKIN, On the Uses of the Spleen. — Edinburgh Medi- cal and Surgical Journal, 1822, vol. xviii., p. 90). 2 The changes in the volume of the spleen have been observed by many physiologists. Bernard noted, in addition, that the blood of the splenic vein is red during abstinence and dark during digestion (Liquides de Vorganisme^ Paris, 1859, tome ii., p. 420). DUCTLESS GLANDS. 345 ance of the functions of digestion and absorption. Experi- ments have shown that animals may live, digest, and absorb alimentary principles perfectly well after the spleen has been removed, and this has even been observed in the human sub- ject ; and in view of these facts, it is impossible to assume that the presence of the spleen, as a diverticulum for the blood, is essential to the proper action of the other abdom- inal organs. Extirpation of the Spleen. — There is one experimental fact that has presented itself in opposition . to nearly every theory advanced with regard to the function of the spleen ; which is, that the organ may be removed from a living ani- mal, and yet all the functions of life go on apparently as before. The spleen is certainly not essential to life, nor, as far as we know, to any of the important general functions. It has been removed over and over again from dogs, cats, and even from the human subject, and its absence is attended with no constant and definite changes in the phenomena of life. If it act as a diverticulum, this function is not essen- tial to the proper operation of the organs of digestion and ab- sorption ; and if its office be the destruction or the formation of the blood-corpuscles, the formation of leucocytes, fibrin, uric acid, cholesterine, or any excrementitious matter, there are other organs which may accomplish these functions. What renders this question even more obscure is the fact that we Ijave no knowledge of any constant modifications in the size or the functions of other organs as a consequence of removal of the spleen.1 This is not surprising, however, when we reflect that one kidney can accomplish the function of uri- 1 Beclard mentions several authorities who have noted enlargement of the lymphatic glands throughout the system, consequent upon removal of the spleen, and one of these instances occurred in the human subject (Traite elemen- taire de physiologic humaine, Paris, 1859, p. 443); but these observations have not been confirmed sufficiently to warrant the supposition that the spleen belongs to the lymphatic system, particularly as its connections with the blood- vessels are very extensive, and its lymphatics are rather scanty. 346 SECEETION. nary excretion after the other has been removed, and that the single organ remaining probably does not undergo en- largement.1 There are certain phenomena that sometimes follow re- moval of the spleen from the lower animals, which are curious and interesting, even if they do not afford much positive information. Extirpation of this organ is an old and a very common experiment. In the works of Malpighi, published in 168T, we find an account of an experiment on a dog, in which the spleen was destroyed, and tho ope- ration was followed by no serious results.3 Since then it has been removed so often, and the experiments have been so universally negative in their results, that it is hardly neces- sary to cite authorities on the subject. There are numerous instances, also, in which it has been in part or entirely removed from the human subject, which it is unnecessary to refer to in detail ; but in nearly every case, when there was no diseased condition to complicate the observation, the result has been the same as in experiments on the inferior animals.3 One of the phenomena to which we desire to call at- tention is the modification of the appetite. Great voracity in animals, after removal of the spleen, was noted by the 1 See page 170. 9 MALPIGHI, De Liene, Opera omnia, Lugd. Batav., 1687, tomus ii., p. 302. 3 In the Union medicate, Paris, 1867, 21me annee, Nos. 141, 142, pp. 340, 373, a case of splenotomy followed by complete recovery is reported by M. Pean. In succeeding numbers of the same journal, M. Magdelain has collected reports of nine cases of splenotomy performed on account of wounds of the abdomen, and six cases in which the spleen had been in part or entirely removed on ac- count of disease. In all the cases of injury, the patients recovered, presenting afterward no unusual symptoms ; but of the six cases of disease of the spleen, four of the patients died (II union medicate, Paris, 1867, Nos. 144, 146, pp. 405, 431). Other cases of removal of the spleen in the human subject are quoted in the New York Medical Journal, 1868, vol. vii., p. 258, et seg. In HALLER, Elementa Physiologies, Bernse, 1764, p. 421, is a full historical account of the early ex- periments on removal of the spleen in the lower animals ; and Prof. Dunglison (Human Physiology, Philadelphia, 1856, vol. i., p. 583, et seg.) gives an account of experiments on animals, and cites numerous instances of its removal or ab- sence in the human subject. DUCTLESS GLANDS. 347 earlier experimenters, and formed the basis of some of their extravagant theories. Boerhaave mentions this fact in his Animal Economy • l and Dumas advances it in support of a theory that the spleen takes up the superabundant portion of the gastric fluid.2 Later experimenters have observed this change in the appetite, and have noted that digestion and assimilation do not appear to be disturbed, the ani- mals becoming unusually fat. Prof. Dalton has also ob- served that the animals, particularly dogs, sometimes present a remarkable change in their disposition, becoming unnatu- rally ferocious and aggressive.* We have frequently observed these phenomena after removal of the spleen ; and in the following experiment, performed in 1861, they were particu- larly marked : The spleen was removed from a young dog weighing twenty-two pounds, by the ordinary method ; viz., making an incision into the abdominal cavity in the linea alba, drawing out the spleen, and exsecting it after tying the vessels. Before the operation the dog presented nothing unusual, either in his appetite or disposition. The wound healed rapidly, and after recovery had taken place, the animal was fed moderately once a day. It was noticed, how- ever, that the appetite was excessively voracious ; and the dog became so irritable and ferocious that it was dangerous to approach him, and it became necessary to separate him from the other animals in the laboratory. He would eat refuse from the dissecting-room, the flesh of dogs, faeces, etc. On February 11, 1861, about six weeks after the operation, having been well fed twenty-four hours before, the dog was brought before the class at the ~New Orleans School of Medi- cine, and ate a little more than four pounds of beef-heart, nearly one fifth of his weight. This he digested perfectly well, and the appetite was the same on the following day. 1 BOERHAAYE, Actio Lienis, (Economia Animalis, London, 1761, p. 80. 8 DUMAS, Principes de physiologic, Paris, 1803, tome iv., p. 611. 8 DALTON, A Treatise on Human Physiology, Philadelphia, 1867, p. 195. 34:8 SECRETION. This dog had a remarkably sleek and well-nourished appear- ance. The above is a striking example of the change in the appetite and disposition of animals after extirpation of the spleen ; but these results are by no means invariable. We have often removed the spleen from dogs, and kept the ani- mals for months without observing any thing unusual ; and, on the other hand, we have observed the change in dis- position and the development of an unnatural appetite, in animals after removal of one kidney ; these effects were also very well marked in an animal with biliary fistula, that lived for thirty-eight days. In the latter instance, the voracity could be explained by the disturbance in digestion and as- similation produced by shutting off the bile from the intes- tine ; but these phenomena occurring after removal of one kidney, which appeared to have no effect upon the ordinary functions, are not so readily understood. "We have observed both increase in the appetite and the development of ex- traordinary ferocity after extirpation of one kidney almost in- variably, since our attention has been directed to this point ; and in those experiments of which records were preserved, these effects were very marked. In one, a dog lived for nearly two years with one kidney, and was finally killed. The appetite was voracious and depraved. He would eat dogs' flesh greedily. In another, death took place in con- vulsions, forty-three days after removal of one kidney, the animal having apparently recovered from the operation. This dog was very ferocious, had an extraordinary appetite, and would eat fasces, putrid dogs' flesh, etc., which the other dogs in the laboratory would not touch. The other dog entirely recovered from the operation of removing one kid- ney, and presented the same phenomena. In view of the above facts, it must be admitted that the removal of the spleen in the lower animals and the human subject has thus far demonstrated nothing, except that this part is not essential to the proper performance of the vital DUCTLESS GLANDS. 34:9 functions. The voracity which occasionally follows the op- eration in animals is one of the phenomena, like the increase in the size of animals after castration, for which physiologists can offer no satisfactory explanation. It is evident from the foregoing considerations that, not- withstanding the great amount of literature on the anatomy and functions of the spleen, physiologists have no definite knowledge of any important office performed by this organ. With this conclusion, we pass to a consideration of the other ductless glands, the physiology of which is, unfortunately, even more unsatisfactory. Suprarenal Capsules. The theories that have been advanced with regard to the function of the suprarenal capsules have not, as a rule, been based upon anatomical investigations, but have taken their origin from pathological observations and experiments on living animals. This fact detracts from the physiological interest attached to the structure of these bodies, and we shall consequently treat of their anatomy very briefly. The suprarenal capsules, as their name implies, are situ- ated above the kidneys. They are small, triangular, flat- tened bodies, placed behind the peritoneum, and capping the kidneys at the anterior portion of their superior ends. The left capsule is a little larger than the right, and is rather semilunar in ^ form, the right being more nearly triangular. Their size and weight are very variable in different individ- uals. Of the different estimates given by anatomists, we may state, as an average, that each capsule weighs about one hundred grains. They are about an inch and a half in length, a little less in width, and a little less than one- fourth of an inch in thickness. The weight of the capsules, in proportion to that of the kidneys, presents great variations at different periods of life ; and they are so much larger in the foetus than after birth, that some physiologists, in default of any reasonable theory 350 SECRETION. of their function in the adult, have assumed that their office is chiefly important in intra-uterine life. Meckel states that they are easily distinguished in the foetus of two months ; at the end of the third month, they are a little larger and heavier than the kidneys ; they are equal in size to the kidneys (though a little lighter) at four months ; and, at the beginning of the sixth month, are to the kidneys as two to five. In the foetus at term, the proportion is as one to three, and in the adult as one to twenty-three.1 It was asserted by some of the older writers, that the capsules are larger in the negro than in the white races, but Meckel states that although he had observed this in a negress, he saw nothing of it in dissecting a negro.2 This observation did not have much significance at that time ; but since it has been supposed that the supra- renal capsules have some function in connection with the for- mation of pigment, authors have quoted it as important. The color of the capsules is whitish yellow. They are completely covered by a thin fibrous coat, which penetrates their interior, in the form of trabeculse. Upon section, they present a distinct cortical and medullary substance. The cortex is yellowish, from -£T to -fa of an inch in thickness, surrounding the capsule entirely, and constituting about two-thirds of its substance. The medullary substance is whitish, very vascular, and is remarkably prone to decompo- sition, so that it is desirable to study the anatomy of these bodies in specimens that are perfectly fresh. /Structure of the Suprarenal Capsules. — These bodies have been closely studied by Frey,3 Ecker,4 Kolliker,5 Har- 1 MECKEL, Manual of General, Descriptive, and Pathological Anatomy, Phila- delphia, 1832, vol. iii., p. 394. 2 Loc. cit. 3 FREY, Cyclopaedia of Anatomy and Physiology, London, 1849-1852, vol. iv., part ii., p. 827, Article, Supra-Renal Capsules. 4 ECKER, Nebennieren, in WAGNER'S Handwdrterbuch der Physiologic, Braun- schweig, 1853, Bd. iv., S. 128, et seq. 5 KOLLIKER, Manual of Human Microscopic Anatomy, London, 1860, p. 421, et seq., and Handbuch der Gewebelehre des Menschen, Leipzig, 1867, S. 514, et seq. DUCTLESS GLANDS. 351 ley,1 and many others. Recently, a very elaborate account of their minute anatomy has been given by M. Grandry.2 The parts examined by M. Grandry were taken from an executed criminal, aged nineteen years, before they had un- dergone any alteration, and were placed immediately in chromic acid. We do not. propose to discuss fully all the minute details or the mooted questions in the anatomy of these parts, for these have very little physiological interest ; and we refer the reader to the authorities just cited for a more complete account of their histology. It is sufficient for us to know that they have no excretory duct, and that their structure resembles that of the other ductless glands. Cortical Substance. — The cortical substance is divided into two layers. The external is pale yellow, and is com- posed of closed vesicles, rounded or ovoid in form, contain- ing an albuminoid fluid, cells, nuclei, and fatty globules. This layer is very thin. The greater part of the cortical substance is of a reddish-brown color, and is composed of closed tubes. On making thin sections through the cortical substance, previously hardened in chromic acid and ren- dered clear by means of glycerine, numerous rows of cells are seen, arranged with great regularity, and extending, apparently, from the investing membrane to the medullary substance. On studying these sections with a high mag- nifying power, it is evident that the cells are enclosed in tubes measuring from 10100 to -3^-5- of an inch in diameter. Harley is of the opinion that these tubes are not simply bounded by fibrous processes from the external coat, but are lined by a structureless membrane.3 This view is confirmed by the more recent observations of M. Grandry, made upon perfectly fresh specimens from the human sub- 1 HARLEY, Histology of the Supra-Renal Capsule*. — The Lancet, London, 1858, vol. L, pp. 551, 576. 4 GRANDRY, Memoire sur la structure de la capsule surrenale de Fhomme et de qudques animaux. — Journal de Canatomie et de la physiologic, Paris, 1867, tome iv.j pp. 225, 389. 3 Loc. cit. 352 SECRETION. ject ; * but it is probably the fact that the rows of cells are enclosed in tubes through a portion only of the cortical sub- stance, the membrane being absent in the deeper layers. The cells are granular, with a distinct nucleus and nucleolus, and a variable number of oil-globules. They measure from TTTO *° TTTUTT °f an mcn m diameter. Grandry describes three kinds of tubes in what he calls the second layer of the cortical substance ; viz., tubes filled with a strongly-refracting mass of needle-shaped crystals, like crystals of fat ; tubes filled with finely-granular, nucleated cells, containing no fat ; and tubes filled with nucleated cells containing numerous fatty granulations.8 Between the tubes of the cortical sub- stance are bands of fibrous tissue, connected with the cover- ing of the capsule. Medullary Substance. — The medullary substance is much paler and more transparent than the cortex. In its centre are numerous openings, marking the passage of its venous sinuses. It is penetrated in every direction by excessively delicate bands of fibrous tissue, which enclose blood-vessels, nerves, and numerous elongated closed vesicles, containing cells, nuclei, and granular matter. These vesicles, -fa of an inch long and about ^-J-^ of an inch broad, have been demon- strated by Grandry in the ox and in the human subject. The cells in the human subject are from 17100 to I210o of an inch in diameter. They are isolated with difficulty, and are very irregular in their form. The nuclei measure about •g-gVff- of an inch.3 The medullary substance is peculiarly rich in vessels and nerves. 1 GRANDRY, op. tit., p. 392. M. Grandry makes three layers in the cortical substance ; but these he found more distinct in the inferior animals than in man. The external layer is composed of one, two, or three rows of rounded or ovoid closed vesicles ; the second layer is formed of tubes ; and the third layer is composed of elements like those contained in the tubes, but not enclosed either in tubes or vesicles. This division into three zones had previously been made by Arnold (Journal of Anatomy and Physiology, London and Cambridge, 1867, vol. i., p. 147; from YIRCHOW'S Archiv, January, 1866). 2 Loc. cit. 3 Op. cit., pp. 232, 398. DUCTLESS GLANDS. 353 Vessels and Nerves. — The blood-vessels going to the supra- renal capsules are very numerous, and are derived from the aorta, the phrenic, the coeliac axis, and the renal artery. Some- times as many as twenty distinct vessels penetrate the capsule. In the cortical substance the capillaries are arranged in elon- gated meshes, anastomosing freely, and surrounding the tubes, but never penetrating them. In the medullary sub- stance the meshes are more rounded, and here the vessels form a very rich capillary plexus. Two large veins pass out, to empty, on the right side, into the vena cava, and on the left into the renal vein. Other smaller veins empty into the cava, the renal, and the phrenic veins. The nerves are very numerous, and are derived from the semilunar ganglia, the renal plexus, the pneumogastric, and the phrenic. Kolliker mentions that he has counted, in the human subject, thirty-three nervous trunks entering the right suprarenal capsule.1 According to Grandry, the nerves pass directly to the medullary substance, but here their mode of distribution is unknown. In the medullary matter, how- ever, are two ganglia, characterized by nerve-cells of the or- dinary form, and situated close to the central vein.3 Nothing whatever is known of the lymphatics of the suprarenal capsules, and the existence of these vessels, even, is doubtful. Chemical Reactions of the Suprarenal Capsules. — A few years ago M. Yulpian discovered in the medullary portion of the suprarenal capsules a peculiar substance, soluble in water and in alcohol, which gave a greenish reaction with the salts of iron and a peculiar rose-tint on the addition of iodine. He could not determine the same reaction with ex- tracts from any other parts.3 Later, in conjunction with M. 1 KOLLIKER, Handbuch der Gewebelehre, Leipzig, 1867, S. 620. 2 Op. cit., p. 400. * VULPIAN, Note sur quelques reactions propres d la substance des corps surre- nates. — Comptes rendus, Paris, 1856, tome xliii., p. 663. 23 354: SECRETION. Cloez, he discovered hippuric and taurocholic acid in the capsules of some of the herbivora.1 Other researches have been made into the chemistry of these bodies, but without results of any great physiological importance. State of our Knowledge concerning the Functions of tJie Suprarenal Capsules. In 1855, the late Dr. Addison, of Guy's Hospital, pub- lished a remarkable memoir on a peculiar disease which he had found connected with disorganization of the suprarenal capsules. This disease, sometimes called Addison's disease, is characterized by bronzing of the skin, and is accompanied by serious disorders in nutrition. It was supposed to be in- variably fatal. The peculiar discoloration of the surface, attended with disorganization of the suprarenal capsules, led physiologists to suppose that, perhaps, these bodies had some function connected with the formation of pigment ; and, fol- lowing the publication of Dr. Addison's memoir, we find quite a number of experiments on animals, consisting chiefly in extirpation of the capsules. Before this time there had been no reasonable theory, even, of the probable function of these bodies. As our first ideas of the relations of the supra- renal capsules to the formation of pigment were derived from cases of disease, it may not be out of place to consider briefly whether there be any invariable and positive connection be- tween structural change in these organs and the affection known under the name of bronzed skin. In the memoir by Dr. Addison, are reported eleven cases of anaemia, accompanied with bronzing of the skin, termi- nating fatally, and found, after death, to be attended with extensive disorganization of the suprarenal capsules.2 The 1 CLOEZ ET VULPIAN, Note sur ^existence des acides hippurique et choleique dans les corps surrenales dcs animaux herbivores. — Comptes rendus, Paris, 1857, tome xlv., p. 340. 2 ADDISON, On the Constitutional and Local Effects of Disease of the Supra- Renal Capsules, London, 1855. DUCTLESS GLANDS. 355 reports of these cases attracted a great deal of attention among physiologists as well as pathologists. A year later, Prof. I. E. Taylor, of Bellevue Hospital, reported seven cases of bronzed skin, in two of which the diagnosis of disease of the suprarenal capsules was verified by post- mortem examination.1 Attention now being directed to this peculiar condition of the system, accompanied with discol- oration of the skin, numerous cases were reported, from time to time, but some of them did not fully carry out the views of Dr. Addison. In 1858, Dr. Harley, in connection with his elaborate researches into the anatomy and physiology of the suprarenal capsules, cited several cases of the so-called Addison's disease, unaccompanied with any disorganization of the capsules, and also several instances in which the cap- sules were seriously invaded by disease, without any bronzing of the skin.2 Perhaps the most extensive collection of cases, however, taken from a great number of authorities, is given by Dr. Greenhow, in a recent work on Addison's disease. Dr. Greenhow is apparently convinced that the connection between the constitutional symptoms and discoloration of the skin, described by Addison, and disorganization of the suprarenal capsules is well established. He reports one hundred and ninety-six cases ; and, out of these, he selects one hundred and twenty-eight, as fair representatives of Ad- dison's disease.3 There are several cases (ten) in which there was bronzing of the skin, the suprarenal capsules being per- fectly healthy ; but in only one of these were there any of the 1 TAYLOR, The Sunburnt Appearance of the Skin as an early Diagnostic Symp- tom of Supra-Renal Capsule Disease. — Reprinted from the New York Journal of Medicine, 1856. 2 HARLEY, An Experimental Inquiry into tftd Functions of the Supra-Renal Capsules, and their Supposed Connexion with Bronzed Skin. — British and Foreign Medico- Chirurgical Review, London, 1858, vol. xxi., pp. 204, 498. Shortly after these papers appeared, we made an editorial analysis of them, in connection with the recent observations of MM. Brown-Sequard, Martin-Magron, Gratiolet, and Philipeaux, in the Buffalo Medical Journal (see vol. xiii., 1858, p. 575, and vol. xiv., p. 175). 3 GREENHOW, On Addison's Disease, London, 1866, p. 47, et seq. 356 SECRETION. characteristic constitutional symptoms.1 There are twenty- two cases cited of cancer of the suprarenal capsules, not one of which presented the characteristic constitutional symp- toms, seven only presenting some slight discoloration of the skin.8 Without discussing this subject more fully, it seems justi- fiable to adopt the opinion, entertained by many pathologists, that there is a connection between bronzed skin accompa- nied with certain grave constitutional symptoms, and disor- ganization of the suprarenal capsules, which is frequent but not invariable ; but it is not established that the destruction of the capsules stands in a causative relation to the discolor- ation or to the constitutional disturbance. It is more interest- ing to us, however, to know that the investigations into these diseased conditions have developed little or nothing of impor- tance concerning the physiology of the suprarenal capsules. Extirpation of the Suprarenal Capsules. — There are two important questions to be settled by the removal of the supra- renal capsules from living animals. The first is, whether or not these organs are essential to life ; and the second is, to determine the consequences of their removal, as exhibited in modifications of the animal functions. The first experi- ments on this subject, by Dr. Brown-Sequard, seemed to show, not only that the suprarenal capsules are essential to life, but that they have an important function connected with the development of pigment. These experiments were in a measure complementary to the pathological observations by Dr. Addison. Are the suprarenal capsules essential to life ? This ques- tion can be answered in a very few words. Dr. Brown- Sequard,8 in his first experiments, removed one and both 1 Op. tit., p. 49. * Op. tit., p. 50. 3 BROWN-SEQUARD, Recherches experimentales sur la physiologie et la pathologic des corps sv,rrenales. — Archives generales de medetine, Paris, 1856, 5me s6rie, tome viii., pp. 385, 572. DUCTLESS GLANDS. 357 capsules in rabbits, Guinea-pigs, dogs, and cats, and the ani- mals died in the course of two or three days. He also noted several peculiar results, as turning, and contraction of the pupil, when one capsule had been extirpated, and the de- velopment of peculiar crystals in the blood. M. Gratiolet repeated these experiments, and ascertained that the left capsule could be removed with impunity, while extirpation of the right was always fatal.1 M. Philipeaux added a num- ber of observations, experimenting chiefly on rats and taking great care to disturb the adjacent organs as little as possible. As the result of these experiments, he concluded that the capsules were not essential to life. Of four rats operated upon in this way, three died, as Philipeaux supposed, of cold, the first in nine days, the second in twenty-three days, and the third in thirty-four days. One was alive and well when the report was made, although the capsules had been removed for forty-nine days.3 The views first advanced by Dr. Brown-Sequard were reiterated by him in a memoir published in the Journal de la physiologie, in 1858, with the modification that the capsules might have no important functions in animals without pigment, as white rabbits and rats, but that they were indispensable to the life of animals not albinos.8 These views, however, were further disproved by Dr. Harley, who made experiments upon a variety of animals, albinos and colored, with the most satisfactory re- sults. Two Guinea-pigs were experimented upon by Dr. Harley, in the following way: In one the abdomen was opened, and the amount of injury which the parts would suffer by removal of the suprarenal capsules was inflicted, the wound was closed, and the capsules allowed to remain ; and the other, of the same age, sex, and development, was 1 GRATIOLET, Note sur les effete qui suivent Variation dcs capsules surrenales. — Comptes rendus, Paris, 1856, tome xliii., p. 469. 2 PHILIPEAUX, Note sur ^extirpation des capsules surrenales chez les rats albino*. — Comptes rendus, Paris, 1856, tome xliii., p. 904. 3 BROWN-SEQUARD, Nouvdles recherches sur ^importance des fonciions des cap? sules surrenales. — Journal de la physiologic, Paris, 1858, tome i., p. 160, at seq. 358 SECRETION. deprived of the capsule on the corresponding side. Both animals died within twenty-four hours. Dr. Harley, among other experiments, took out both capsules from a piebald rat. The left was removed six weeks after the right. The ani- mal entirely recovered and became fat and healthy looking.1 In such a question as this, negative experiments are of little account ; and the instances in which animals have re- covered and lived perfectly well after removal of both supra- renal capsules show conclusively that they are not essential to life. Death has probably been due, in most of the experi- ments, to injury of the semilunar ganglia, as suggested by Dr. Harley, and it is probably on account of the greater in- jury, from the situation of the capsule, produced by opera- ting on the right side, that the remoyal of the capsule on that side is more generally fatal. It is not necessary to take account, in this connection, of the contraction of the pupil, " turning " and other symptoms referable to the nervous system, which have sometimes fol- lowed these operations. These phenomena are undoubtedly due to injury of adjacent parts, and not to extirpation of the capsules. The only remaining question to determine is whether the capsules have any thing to do with the formation or change of pigment. Notwithstanding the assertion of Dr. Brown-Sequard, that flakes of pigment and blood-crys- tals differing from those found in normal blood are found in animals deprived of the suprarenal capsules, this view is adopted by few physiological authorities. Longet cites the observations of Martin-Magron,3 who examined daily, with the greatest care, the blood of a cat that lived two months after extirpation of the capsules, and could never determine the pigmentary matters described by Brown- 1 HARLEY, An Experimental Inquiry into the Functions of the Supra-Renal Capsules, and their Supposed Connexion with Bronzed Skin. — British and Foreign Medico- Chirurgical Review, London, 1858, vol. xxi., p. 204, etseq. 2 LONGET, Traite de physiologic, Paris, 1869, tome ii., p. 392. It does not appear from this quotation that the experiments of Martin-Magron were ever published elsewhere. DUCTLESS GLANDS. 359 Sequard. Dr. Harley, also, in one of the experiments in which the animal died, failed to find pigmentary mat- ter.1 In view of these facts, and in the absence of comparative examinations of the blood going to the suprarenal capsules by the arteries and returned from them by the veins, it is impossible to assign any definite function to these bodies, and it is certain that they are not essential to life. Their greater relative size before birth has led to the supposition that they might have an important office in intra-uterine life, but this is a pure hypothesis, based upon no positive knowledge. Thyroid Gland. The history of this gland belongs almost exclusively to descriptive anatomy ; and its only physiological interest is in the similarity of its structure to that of the other ductless glands. It has no excretory duct. It is attached to the lower part of the larynx, following it in its various move- ments. Its color is brownish-red. The anterior face is con- vex, and is covered by certain of the muscles of the neck. The posterior surface is concave, and is applied to the larynx and trachea. It is formed of two lateral lobes, with a rounded, thickened base below, and a long, pointed extremity extend- ing upward, connected by an isthmus. Each of these lobes is about two inches in length, three-quarters of an inch in breadth, and about the same in thickness at its thickest por- tion. The isthmus connects the lower portion of the lateral lobes. It covers the second and third tracheal rings, and is about half an inch wide and one-third of an inch thick. From the left side of the isthmus, and sometimes from the left lobe, is a portion projecting upward, called the pyramid. The weight of the thyroid gland, according to Sappey, is from three hundred and fifty to three hundred and eighty grains. It is usually stated by anatomical writers that it is relatively 1 Loc. dt. SECRETION. larger in the foetus, and in early life, than in the adult ; but Sappey, from his own researches, is disposed to believe that its weight, in proportion to the weight of the adjacent organs, does not vary with age.1 It is a little larger and more promi- nent in the female than in the male. Structure of the Thyroid Gland. — The gland is covered with a thin but resisting coat of ordinary fibrous tissue, which is loosely connected with the surrounding parts. From the internal surface of this membrane are numerous fibrous bands, or trabeculae, giving off, as they pass through the gland, sec- ondary trabeculse, and then subdividing, until they become microscopic. By this arrangement, the gland is divided up into communicating cells, like a sponge. These bands are mingled with numerous small elastic fibres. Throughout the substance of the gland, lodged in the meshes of the tra- beculae, are numerous rounded or ovoid closed vesicles, meas- uring from ^-J-g- to -g-J-g- of an inch. These are formed of a structureless membrane, and lined by a single layer of pale, granular, nucleated cells, from 3^0 to g^ of an inch in diameter.3 The layer of cells sometimes lines the vesicle completely, sometimes it is incomplete, and sometimes it is wanting. The contents of the vesicles are a clear, yellowish, slightly viscid, albuminoid fluid, with a few granules, pale cells, and nuclei. Robin has described in these vesicles some curiously-shaped, translucent, feebly-refracting, colorless bodies which he lias called sympexions ; but little is known of their constitution or properties.3 The vesicles are arranged in little collections or lobes, with the great veins passing be- tween them. Vessels and Nerves. — The blood-vessels of the thyroid gland are very numerous, it being supplied by the superior 1 SAPPEY, Traite d'anatomie descriptive, Paris, 1857, tome iii., p. 447. 2 KOLLIKER, Handbuch der Gewebelehre des Menschen, Leipzig, 1867, S. 481. 8 LITTRE ET ROBIN, Dictionnaire de medecine, Paris, 1855, Articles, Sym- pexion and Thyrco'ide. DUCTLESS GLANDS. 361 and inferior thyroid arteries, and sometimes a branch of the innominata. The arteries break up into a close capillary plexus, surrounding the vesicles with a rich net-work, but never penetrating their interior. The veins are large, and, like the hepatic veins, are so closely adherent to the sur- rounding tissue, that they do not collapse when cut across. The veins emerging from the gland form a plexus over its surface and the surface of the trachea, and then go to form the superior, middle, and inferior thyroid veins. The nerves are derived from the pneumogastric and the cervical sym- pathetic ganglia. The lymphatics are numerous, but are difficult to inject. The exact distribution of the nerves and the origin of the lymphatics are not well understood. State of our Knowledge concerning the Functions of the Thyroid Gland. — It is generally admitted that the thyroid gland may be removed from animals without interfering with any of the vital functions ; and this, taken in connec- tion with the fact that it is so often diseased in the human subject, without producing any general disturbance, shows that its function cannot be very important. Nothing of im- portance has been learned from a chemical analysis of its substance. The blood of the thyroid veins has been analyzed by Colin and Berthelot, but the changes in its composition in passing through the gland are slight and indefinite.1 An instance is quoted by Longet of periodical enlargement of the gland in a female during menstruation,* but there is no evidence that this is of constant occurrence. Thymus Gland. The anatomy of the thymus assimilates it to the ductless glands, but its function, whatever it may be, is confined to early life. In the adult the organ is wanting, traces, only, of fibrous tissue, with a little fat, existing after puberty in 1 COLIN, Traite de physiologic comparee, Paris, 1856, tome ii., p. 479. 8 LONGET, Traite de physiologic, Paris, 1869, tome ii., p. 398. 362 8ECKETION. the situation previously occupied by this gland. As there never has been a plausible theory, even, of the function of this organ, the existence of which is confined to the first two or three years of life, we shall abstain from all discussions with regard to minute points in its anatomy, and give a sim- ple sketch of its structure, as compared with the ductless glands already considered. The thymus appears about the third month of foetal life, and gradually increases in size until about the end of the second year. It then undergoes atrophy, and disappears al- most entirely at the age of puberty. It is situated partly in the thorax and partly in the neck. The thoracic portion is in the anterior mediastinum, resting upon the pericardium, extending as low as the fourth costal cartilage. The cervical portion extends upward as far as the lower border of the thyroid. The whole gland is about two inches in length, one and a half inches broad at its lower portion, and about one-quarter of an inch thick. Its color is grayish, with a slight rosy tint. It is usually in the form of two lateral lobes, lying in apposition in the median line, though some- times there exists but a single lobe. It is composed of nu- merous lobules, held together by fibrous tissue. The proper coat of the thymus is a delicate fibrous mem- brane, sending processes into the interior of the organ. Its fibrous structure, however, is loose, so that the lobules can be separated with little difficulty. Portions of the gland may be, as it were, unravelled, by loosening the interstitial fibrous tissue. In this way it will be found to be composed of numerous little lobular masses, attached to a continuous cord. This arrangement is more distinct in the inferior ani- mals of large size than in man. The lobules are composed of rounded vesicles, from ten to fifteen in number, and from T2T ^0 iV °f an mcn in diameter. The walls of these vesicles are thin, finely granular, and excessively fragile. The vesi- cles contain a small quantity of an albuminoid fluid, with cells and free nuclei. The cells are small and transparent, DUCTLESS GLANDS. 363 and the nuclei, spherical, relatively large, and containing from one to three nucleoli. The free nuclei are also rounded and contain several distinct nucleoli. These vesicles are easily ruptured, when their contents exude in the form of an opa- lescent fluid, sometimes called the thymic juice. Anatomists are somewhat divided in their opinions with regard to the structure of the central cord and lobules. Some adopt the view advanced by Sir Astley Cooper,1 that the cord has a central canal, connected with cavities in the lobules ; 8 while others believe that the cavities thus described are pro- duced artificially, by the processes employed in anatomical investigation.3 The latter opinion is the latest, and is prob- ably correct. The blood-vessels of the thymus are numerous, but their calibre is small, and the gland is not very vascular. They are derived chiefly from the internal mammary artery, a few coming from the inferior thyroid, the superior diaphragmatic, or the pericardial. They pass between the lobules, surround and penetrate the vesicles, and form a capillary plexus in their interior. The vesicles, in this respect, bear a certain resemblance to the closed follicles of the intestine. The veins are also numerous, but they do not follow the course of the arteries. The principal vein emerges at about the centre of the gland, posteriorly, and empties into the left brachio- cephalic. Other small veins empty into the internal mam- mary, the superior diaphragmatic, and the pericardial. A few nervous filaments from the sympathetic system surround the principal thymic artery, and penetrate the gland. Their ultimate distribution is uncertain. The lymphatics are very numerous.4 Inasmuch as the thymus is peculiar to early life, one of 1 COOPER, Anatomy of the T/iymus Gland, London, 1832, p. 26, et seq. 8 Cyclopaedia of Anatomy and Physiology, London, 1849-1852, vol. iv., Part ii., p. 1087, Article, Thymus. * SAPPEY, Traite tfanatomie descriptive, Paris, 1857, tome iii., p. 456, and LITTRE ET ROBIN, Dictionnaire de medecine, Paris, 1865, Article, Thymus. 4 KOLLIKER, ffandbuch der Gewebelehre des Menschen, Leipzig, 1867, S. 485. 364: SECRETION. the most interesting points in its anatomical history relates to its mode of development. This, however, does not pre- sent any great physiological importance, and is fully treated of in works upon anatomy.1 Pituitary Body and Pineal Gland. These little bodies, situated at the base of the brain, are quite vascular, contain closed vesicles and but few nervous elements, and are sometimes classed with the ductless glands. Physiologists have no idea of their function. The pituitary body is of an ovoid form, a reddish-gray color, weighs from five to ten grains, and is situated in the sella turcica of the sphenoid bone. It is said to be larger in the foetus than in the adult, and at that time has a cavity communicating with the third ventricle.8 Ecker describes it as containing the elements of a blood-gland.3 This little body has lately been studied by M. Gran dry, in connection with the suprarenal capsules. He regards it as essentially com- posed of closed vesicles, with fibres of connective tissue and blood-vessels. The vesicles measure from -g^-g- to y^-g- of an inch in diameter. They are formed of a transparent mem- brane, containing irregularly polygonal, nucleated cells, and free nuclei. The cells are from ^^ to yyVg- of an inch in diameter. The nuclei are distinct, with a well-marked nu- cleolus, and measure about -g-jnnj- of an inch. Capillary ves- sels surround these vesicles, without penetrating them. M. Grandry did not observe either nerve-cells or fibres between the vesicles.4 In old subjects he found the peculiar concre- 1 For the history of the development of the thymus, the reader is referred to special treatises. A very full account of its development is given by Dr. Handfield Jones, in the Cyclopaedia of Anatomy and Physiology, London, 1849- 1852, vol. iv., Part ii., p. 1087, et seq. 2 GRAY, Anatomy, Descriptive and Surgical, Philadelphia, 1862, p. 519. 3 ECKER, in WAGNER, Handworterbuch der Physiologic, Braunschweig, 1853, Bd. iv., S. 161. 4 GRANDRY, Glande pituitaire. — Journal de V anatomic, Paris, 1867, tome iv., p. 400, et seq. DUCTLES8 GLANDS. 365 tions (sympexions) already described as existing in the thy- roid.1 The pineal gland is situated just behind the posterior commissure of the brain, between the nates, and is enclosed in the velum interposition. It is of a conical shape, one- third of an inch in length, and of nearly the color of the pituitary body. It is connected with the base of the brain by several delicate commissural peduncles. It presents a small cavity at its base, and frequently contains in its sub- stance little calcareous masses, composed of phosphate and carbonate of lime, phosphate of magnesia and ammonia, and a small quantity of organic matter.a It is covered with a fibrous envelope, which sends processes into its interior. As the result of the researches of M. Grandry, it has been found to present a cortical substance, entirely analogous in its structure to the pituitary body, and a central portion, com- posed of the ordinary nervous elements found in the gray matter of the brain. Its structure is regarded by Grandry as very like that of the medullary portion of the suprarenal capsules.3 It is difficult to classify organs, of the function of which we are entirely ignorant; but the structure of the little bodies just described certainly resembles that of the duct- less glands. We have only indicated their anatomy to show that their function is probably analogous to that of the other organs of the same class. 1 See page 360. 8 GRAY, op. rit., p. 528. 3 GRANDRY, Glande pineale. — Journal de fanatomie, Paris, 1867, tome iv., p. 405, et seq. CHAPTEK XII. NUTRITION. Nature of the forces involved in nutrition — Protoplasm — Definition of vital properties — Life, as represented in development and nutrition — Principles which pass through the organism — Principles consumed in the organism — Nitrogenized principles — Development of power and endurance by exercise (Training) — Non-nitrogenized principles — Formation and deposition of fat — Conditions under which fat exists in the organism — Physiological anatomy of adipose tissue — Conditions which influence nutrition — Products of dis- assimilation. NUTRITION proper, in the light in which we propose to consider it in this chapter, is the process by which the phys- iological decay of the tissues and fluids of the body is com- pensated by the appropriation of new matter. All of the physiological processes that we have thus far studied, in- cluding circulation, respiration, alimentation, digestion, ab- sorption, and secretion, are to be viewed in the light of means directed to a single end ; and the great function, to which all the others are subservient, is the general process of nutrition. The nature of the main forces involved in nutrition, be it in a highly-organized part, like the brain or muscles, or a tissue called extra-vascular, like the cartilages or nails, is unknown. The phenomena attending the general process, however, have been studied most carefully, and certain im- portant positive results have been attained ; but we find no more satisfactory explanation of the nature of the causative force of nutrition in the doctrines of to-day than in the speculative theories of Pythagoras. GENERAL CONSIDERATIONS. 367 We can hardly realize the vast extent of the problem of nutrition from a review of the functions which we have al- ready considered. We have seen that the blood contains all the elements that enter into the composition of the tissues and secretions, either identical with them in form and composition, as is the case with the inorganic principles, or in a condition which allows of their transformation into the characteristic principles of the tissues, as we see in the organic substances proper. These materials are supplied to the tissues, in the required quantity, through the circulatory apparatus; and the oxygen, which is immediately indispensable to all the operations of life, is introduced by respiration. The great nutritive fluid, being constantly drawn upon by the tissues for materials for their regeneration, is kept at the proper standard by the introduction of new matter into the system, in alimentation, its elaborate preparation by digestion, and its appropriation by the fluids by absorption. These pro- cesses, many of them, require the action of certain secre- tions. The introduction of new matter, so essential to the continuance of the phenomena of life, is demanded, on ac- count of the change of the substance of the tissues into what we call effete matter ; and this is discharged from the animal organism, to be appropriated by vegetables, and thus main- tain the equilibrium between these two great kingdoms in Nature. What is it that causes the parts of a living animal organ- ism to undergo change into effete matter, incapable of any further animal functions ; and what is it that gives to these parts the power of self-regeneration, when new matter is presented under proper conditions ? These questions are the physiological ignis fatuus, which, it is to be feared, will forever elude the grasp of scientific in- quiry. They constitute one of the great mysteries ever pres- ent in the minds of the student of Nature, and one, the gran- deur of which is so immense that it is a problem with which our intelligence can scarcely grapple. Its greatness is com- 368 NUTRITION. mensurate with that of the question of the soul, and its rela- tions to the finite and the infinite ; a question which philoso- phers have been constrained either to admit upon the faith of revelation, or to hopelessly abandon. Little, if any, real progress is to be made by endeavoring to cover the inscruta- ble problem of life with a simplicity entirely artificial. This will always be attractive, and, to a certain extent, satisfac- tory to the minds of those unacquainted with the details of natural laws, or willing to admit speculative theories upon subjects concerning which it is impossible, in the present condition of science, to have any positive information ; and, if generally admitted by biological students, would carry our science back to the dark periods in its history, when the study of Nature was confined to speculation, and there ex- isted no knowledge based upon the direct observation of phenomena. A new name, arbitrarily applied to organic matter, without any addition to its physiological history, does not advance our definite knowledge. For example, it has long been known that certain nitrogenized constituents of the organism, classed collectively as organic principles, seem to give to the tissues their property of self-regeneration and development. It may seem to those not engaged in scientific inquiry that a recital of the wonderful properties of " protoplasm " affords some additional information con- cerning the phenomena observed in organized bodies ; but the true definition of the term leads us back to our former ideas of the so-called vital properties of organic matters.1 It is a well-established fact that while nearly all of the tissues undergo disassimilation, or conversion into effete matter, during their physiological decay in the living organ- ism, others, like the epidermis and its appendages, are 1 HUXLEY, The Physical Basis of Life, New Haven, 1869,— from the Fort- nightly Review, for February, 1869. This very interesting and able discourse, delivered originally before a popular audience, is referred to, not as a subject for rigid scientific criticism, but as formularizing some of the prevalent ideas concerning the properties of the so-called protoplasm. GENERAL CONSIDERATIONS. 369 gradually desquamated, and, when once formed, do not pass through any further changes. An attempt has been made by Dr. Beale to distinguish in all the tissues a matter en- dowed with the so-called vital properties, which he calls ger- minal matter, and a "formed material," which is passive and cannot become the seat of vital actions.1 Under this idea, the functions of nutrition and development are performed ex- clusively by germinal matter. This theory has been adopted by few physiologists ; and we cannot but regard such a divi- sion as purely anatomical and artificial, as far as the physiology of nutrition is concerned. It is hardly more than a new statement of the old idea of the activity of the nucleus in the process of cell-development. TVe are not called upon to enter into an extended discussion of this ques- tion, until some facts are brought forward which would render such an hypothesis probable. The whole question of the essence and nature of the nutritive property or force resolves itself into vitality. Life is always attended with what we know as the phenomena of nutrition, and nutrition does not exist except in living organ- isms. When we can state positively what is life, we will know something of nutrition. At present, physiologists have only been able to define life by a recital of certain of its invariable and characteristic attendant conditions ; and yet there are few, if any, definitions of life — regarding it as the sum of the phenomena peculiar to living organisms — that are not open to grave objections. If we regard life as a principle, it stands in the relation of a cause to the vital phenomena ; if we regard it as the totality of these phenomena, it is an effect. If we study the development of a fecundated ovum, life seems to be a principle, giving the wonderful property of appropriating matter from without, until the germ be- comes changed, from a globule of microscopic size and an 1 TODD, BOWMAN, AND BEALE, The Physiological Anatomy and Physiology of Man, London, 1866, p. 87. 24 370 NUTRITION. apparently simple structure, into a complete organism, with highly-elaborated parts. This organism has a definite form and size, a definite period of existence, and produces, at a certain time, generative elements, capable of perpetuating its life in new beings. We may say that an organism dies physiologically because the vital principle, if we ad- mit the existence of a principle, has a limited term of existence. But, on the other hand, the fully-developed living organism, which we call an animal, presents numerous distinct parts, each endowed with an independent property called vital, that property recognized by Haller in various tissues, under the name of irritability ; and it is the coor- dinated sum of these vitalities that constitutes the perfect being. These are more or less distinct ; and we do not com- monly observe a sudden and simultaneous arrest of the vital properties in all the tissues, in what we call death. For example, the nerves may die before the muscles, or the mus- cles, before the nerves. It is also found that vital properties, apparently lost or destroyed, may be made to return ; as in resuscitation after asphyxia, or the restoration of muscular or nervous irritability by injection of blood. The life of a fecundated ovum is the property which enables it to undergo a certain development when placed under favorable conditions ; and, by the surrounding condi- tions, its development may be arrested, suspended, or modi- fied. The life of a non-fecundated ovum is like that of any ordinary anatomical element. The life of an anatomical element or tissue in process of development is the property by virtue of which it arrives at its perfection of organization, and performs certain defined func- tions, as far as its organization will permit. This can also be destroyed, suspended, or modified by surrounding conditions. The life of a perfect anatomical element or tissue is the property which enables it to regenerate itself and perform its functions, subject, also, to modifications from surrounding conditions. PRINCIPLES WHICH PASS THROUGH THE ORGAXISM. 371 The life of a perfect animal organism is the sum of the vitalities of its constituent parts ; but a being may live with the vitality of certain parts abolished or seriously modified, as a man exists and preserves his identity with a limb am- putated. Life may continue for a long time without consciousness, or with organs paralyzed or their function destroyed ; but certain functions, such as respiration or cir- culation, are indispensable to the nutrition of all parts, and the vitality of the different tissues is speedily lost when these processes are arrested, and the being then ceases to exist. These considerations make it evident that it is difficult, if not impossible, to give a single comprehensive definition of life, a study of the varied phenomena of which con- stitutes the science of physiology. The general process of nutrition begins with the intro- duction of matter from without, called food. It is carried on by the appropriation of this matter by the organism. It is attended with the production of excrementitious prin- ciples, and the development of certain phenomena that we have not yet studied, the most important of which is the production of heat. We shall have little to say about food, beyond what we have already considered under the head of alimentation, except to classify the alimentary principles with reference to their relations to the general process of nutrition. Principles which pass through the Organism. All of the inorganic principles taken in with the food pass out of the organism, generally in the form in which they enter, in the faeces, urine, and perspiration ; but it must not be inferred from this fact that they are not useful as con- stituent parts of the body. Some of these principles, such as water and the chlorides, have very important functions of a purely physical nature. It is necessary, for example, that the blood should contain a certain proportion of the 372 NUTRITION. chloride of sodium, this substance modifying and regulating the processes of absorption and probably of assimilation. In addition, however, we find the chlorides as constituent parts of every tissue and organ of the body, and so closely united with the nitrogenized principles, that they cannot be completely separated without incineration. Those inorganic matters, the function of which is so marked in their passage through the body, are found largely as constituents of the fluids, and are less abundant in the solids. They are con- tained in quantity, also, in the liquid excretions ; and any excess over the amount actually required by the system is thrown off in this way. Other inorganic matters are espe- cially important as constituent parts of the tissues, and are more abundant in the solids than in the fluids. Examples of principles of this class are the salts of lime, particularly the phosphates. These are also in a condition of intimate union with organic matter, and accompany these principles in all of their so-called vital acts. If we except certain simple chemical changes, such as the decomposition of the bicarbonates, the inprganic elements of food do not necessarily undergo any modification in the pro- cess of digestion. They are generally introduced already in combination with organic matter, and accompany it in the changes which it passes through in digestion, assimilation by the blood, deposition in the tissues, and the final trans- formations that result in the various excrementitious mat- ters ; so that we find the inorganic principles united with the organic matter of the food as it enters the body, and what seem to be the same principles in connection with the or- ganic excrementitious matters; but between these two extremes, are the various operations of assimilation and dis- assimilation, from which inorganic matter is never absent. We have already referred to these facts so often, under the heads of proximate principles, alimentation, digestion, and excretion, that it is unnecessary, in this connection, to dis- cuss them more fully. NTTKOGENIZED PRINCIPLES. 373 Various combinations of bases with organic acids taken as food, as the acetates, tartrates, etc., found in fruits, undergo decomposition in the body, and are transformed into carbonates. In this form they behave precisely like the other inorganic salts.1 Principles consumed by the Organism. All of the assimilable organic matter taken as food is con- sumed in the organism ; and none is ever discharged from the body, in health, in the form under which it was introduced. The principles thus consumed in nutrition have been di- vided into nitrogenized and non-nitrogenized ; and, although they both disappear in the organism, they possess certain marked differences in their properties, and probably, also, in their relations to nutrition. Nitrogenized Principles. — The nitrogenized principles, having for their basis, carbon, hydrogen, nitrogen, and oxy- gen, undergo, in the process of digestion and absorption, remarkable changes ; but these are more marked with rela- tion to their properties than their ultimate chemical com- position. They are all converted into the nitrogenized elements of the blood, which, in their turn, are transformed into the characteristic nitrogenized principles of the different tissues, and are appropriated by these tissues, to supply the place of worn-out matter. With the intimate nature of this series of transformations, we are entirely unacquainted ; but we know that the deposition of new nitrogenized matter in the tissues, constituting one of the most important of the 1 It is a fact well established that the ingestion of certain salts of vegetable origin produces alkaline carbonates of the same bases, which are discharged in the excretions. The replacement of the vegetable acid in this way by carbonic acid, which is weaker, is supposed by Milne-Edwards to be due to the action of the oxygen in the process of respiration. This explanation is not very satis- factory, but the fact of the production of the alkaline carbonates from the vegetable acid salts cannot be doubted ( MILNE-EDTTARDS, Lemons sur la physio- logic, Paris, 1862, tome vii., p. 531). 374 NUTRITION. acts of nutrition, is attended with a corresponding loss of matter that has become changed into the nitrogenized ele- ments of excretion. It is the intermediate series of phe- nomena that is so obscure. The nutrition of the nitrogenized elements of the tissues may be greatly modified by the supply of new matter. For example, a diet composed of nitrogenized matter in a readily assimilable form will undoubtedly affect favorably the devel- opment of the corresponding tissues of the body ; and, on the other hand, a deficiency in the supply will produce a corre- sponding diminution in power and development. The modi- fications in nutrition due to supply have, however, certain well-defined limits. An excess taken as food is not discharged in the faeces, nor does it pass out in the form in which it entered in the urine ; but it apparently undergoes digestion, becomes absorbed by the blood, and increases the quantity of nitrogenized excrementitious matter discharged, particu- larly the urea. This fact is shown by the great increase in the elimination of urea produced by an excess of nitrogen- ized food.1 Whether the nitrogenized matter that is not actually needed in nutrition be changed into urea in the blood, or whether it be appropriated by the tissues, increas- ing the activity of their disassitnilation, is a question difficult to determine experimentally. Certain it is, however, that an excess of nitrogenized food is thrown off in nearly the same way as an excess of inorganic matter ; the difference being that the latter passes out in the form in which it has entered, and the former is discharged in the form of nitro- genized excrementitious matter. Development of Power and Endurance ly Exercise and Diet (Training). — The nutrition of the nitrogenized ele- ments of the body is greatly influenced by functional exercise. This is partly local and partly general in its effects. For example, by the persistent exercise of particu- 1 See page 225. NITEOGENIZED PRINCIPLES. 375 lar muscles, their development can be carried to a high degree of perfection, the rest of the muscular system under- going no change ; or the entire muscular system may, by appropriate general exercise, be made to increase consider- ably in volume, and a person may become capable of great endurance, under an ordinary diet. It is surprising, some- times, to see how small an amount of well-regulated exercise will accomplish this end. But if it be desired to attain the maximum of strength and endurance, it is necessary to carefully regulate the diet as well as the exercise. Those who are in the habit of " training " men, particularly for pugilistic encounters, have long since demonstrated prac- tically certain facts which physiologists have been rather slow to appreciate. By carefully regulating the diet, con- fining it chiefly to nitrogenized articles, eliminating fat entirely, and reducing the starchy elements to the minimum ; by regulating the exercise so as to increase the nutritive activity of all the muscles to the greatest possible extent ; by increasing the respiratory activity by running, etc., and removing from the body all the unnecessary adipose tissue ; by all these means, which favor nutritive assimilation by the nitrogenized elements of the organism, a man may be u trained " so as to be capable of immense muscular effort and endurance. The process of training, skilfully carried out, is in accordance with what are now admitted as physiological laws ; though it has been practised for years by igno- rant persons, and its rules are entirely empirical. It is stated that the athletes of ancient times, while vigorously exercising the muscles, favored by their diet the development of fat, so as to be better able to resist the blows of their an- tagonists.1 However this may be, since the English prize-ring has been regularly organized, or since about the middle of the last century, the system of training has been entirely differ- ent, and fat has been, as far as possible, removed from every 1 HARRISON, Athletic Training and Health, Oxford and London, 1869, p. 87. 376 NUTRITION. part of the body. Fat is regarded by trainers as inert mat- ter ; and they recognize, practically at least, the fact that the characteristic functions of parts depend for their activity upon their nitrogenized constituents. The contraction of a muscle, for example, is powerful in proportion to the amount and condition of its musculine ; and it has been found, prac- tically, that the muscular system can be most thoroughly de- veloped by carefully graduated exercise and a diet composed largely of nitrogenized matter. In the regular system of training, starch, sugar, fat, and liquids are avoided ; and the diet is confined almost entirely to rare meats, eggs, and stale bread or toast, with oatmeal-gruel. The oatmeal has been used from time immemorial, and is supposed to be useful in keeping the bowels in good condition. A very small amount of alcohol and other nervous stimulants, chiefly in the form of home-brewed ale, sherry wine, and tea, are allowed. Sexual intercourse and all unusual ner- vous excitement are interdicted. Those who adopt absolutely the classification of food into plastic, or tissue-forming, and calorific, or respiratory, would regard this course of diet as eminently plastic ; but during the severe habitual exercise, which is most rigid after the man has been " trained down " so that his fat is reduced to the minimum, the respiratory power and the exhalation of carbonic acid are immensely increased, while the proportion of hydro-carbons in the food is very small. "We do not, of course, propose to discuss from a scientific point of view all of the minutiae of training. Many of its traditional rules are trivial and unimportant j l but it is cer- 1 A very curious account of training, the more interesting as it contains the essentials of the methods employed at the present day, is to be found in a book on pugilism, called JBoxiana. This work is attributed to the celebrated Captain Barclay (T/ie Art of Training. — JBoxiana ; or Sketches of Modern Pugilism, con- taining all the Transactions of note connected with the Prize-Ring, during the Years 1821, 1822, 1823, London (no date). The subject of training has at- tracted considerable attention within the last few years in connection with boating; but the brutal practice of prize-fighting affords, probably, the best examples of strength, endurance, and nervous energy. NITBOGKSnZED PRINCIPLES. 377 tainly a question of great physiological interest to study the processes by which the muscular strength' and endurance of a man may be brought to the highest point of devel- opment. One of the most remarkable of the results of thorough training is the development of immense endurance and " wind." This is accomplished by running and prolonged exercise, not so violent as to be exhausting, and always fol- lowed by ablutions and frictions, so as to secure a full re- action. The surprising faculty of endurance thus developed must be due in a great measure to nervous power as well as to gradual, careful, and perfectly physiological development of the muscular system. A man may be brought into the ring in what would appear to be perfect condition ; but if he be trained down too much or too rapidly, he is liable to give out after comparatively slight exertion. A man who does not possess the required constitutional stamina and ner- vous power is likely to break down in training, and can- not be brought to proper condition. On the other hand, a man in perfect condition is capable of the maximum of muscular exertion for an hour, or can walk a hundred miles in a day. It is a question of great importance, in connection with the subject of nutrition, to determine whether the extraordi- nary muscular power developed by severe training be, in the end, beneficial or deleterious. This can be answered very easily upon practical as well as theoretical grounds. A fully- grown, well-developed man, in perfect health, may be trained so as to be brought to what is technically called fine condi- tion, and he will present at that time all the animal func- tions in their perfection. He is then a model of a physical man ; and the only consequences that can result from such a course are beneficial. The argument that professional pugilists are short-lived is fallacious ; for it is well known that almost all of them, after training for and passing through an encounter, immediately relapse into a course of 378 NUTRITION. life, in which all physiological laws are habitually violated. During training, even of the most severe character, not only is great attention paid to diet and exercise, but all of the func- tions are scrupulously watched. Tranquillity of mind, avoid- ance of exhaustion, of artificial excitement, stimulants, tobac- co, etc., are strictly enjoined ; and the process is always very gradual, especially at its commencement, and is continued for several months. The cases in which training has been followed by bad effects are entirely different. Undeveloped boys are frequently trained for boating, in the most reckless manner, until they break down. An attempt is made to accomplish in a few weeks what can only be done physio- logically in several months ; and the result is, that some of the vital organs, particularly the heart, are liable to become permanently injured. To improve the " wind " and endur- ance, a person undergoes the most violent exercise, which is followed by great exhaustion, intense respiratory distress, and disturbance of the action of the heart, these vital parts being suddenly forced far beyond their functional capacity. This cannot be done without danger of permanent disturb- ances of the system, such as have been frequently observed ; and it is all the more liable to be followed by bad results, from the fact that amateurs are trained together, five or six under one man, and are more or less independent, while the professional is never out of the sight of his trainer for months, and during that time is under complete control. There is, it seems, every physiological reason to believe that it is bene- ficial to the general system to bring it to the highest point of functional activity by training ; but if this be not done with great caution and judgment, it is liable to be followed by serious results. Non-Nitrogenized Principles. — The non-nitrogenized principles present a marked contrast to the alimentary sub- stances we have just considered. In the first place, they are not indispensable to the nutrition of all animals. The car- NON-XITROGEXIZED PRINCIPLES. 379 nivora, for example, may be well nourished upon a diet com- posed exclusively of nitrogenized matter ; and the remarks we have just made upon training show that the human subject may be brought to a high condition of physical development, when starch, sugar, and fat are almost en- tirely eliminated from the food. This shows conclusively that the division of the food into plastic and calorific ele- ments is not absolute, and that the animal temperature may be maintained without the hydro-carbons. The nitro- genized principles certainly are the only class of alimentary substances capable of forming muscular tissue ; but, by cer- tain transformations, with the exact nature of which we are imperfectly acquainted, this class of substances is capable of producing heat and of furnishing the carbonic acid elimi- nated in respiration. The non-nitrogenized principles are incapable in themselves of meeting the nutritive demands of the system, and they are either consumed without form- ing part of the tissues, or are deposited in the form of fat. These questions we have already considered fully under the head of alimentation ; and it will be remembered that, with a few exceptions, fat always exists in the body uncombined, either in the form of adipose tissue or fatty granulations in the substance of other tissues. The non-nitrogenized elements taken up by the blood may be divided into two varieties : one, the sugars, com- posed of carbon with hydrogen and oxygen in the propor- tions to form water, constituting the true hydro-carbons ; and the other, the fats, in which the hydrogen and oxygen do not exist in the proportion to form water. "We speak of the sugars only, because starch and all varieties of sugar taken as food are transformed into glucose. In connection with the study of proximate principles, ali- mentation, and glycogenesis, we have already referred to the destination of the true hydro-carbons in the organism. They are taken as food to a considerable extent, particularly in the form of starch, and are formed constantly by the liver, in all 380 NUTRITION. classes of animals. Sugar is never discharged from the body in health,1 nor is it deposited in any part of the organism, even as a temporary condition. It generally disappears in the pas- sage of the blood through the lungs. How is sugar destroyed, and what relation does it bear to nutrition ? In studying the changes which it is capable of passing through, it has been found that it may be converted into lactic acid, or be changed into carbonic acid and water ; but precisely to what extent the sugars undergo these changes, or how they are acted upon by the inspired oxygen, it has been impossible thus far to deter- mine. "We must be content to say that the exact changes which the sugars undergo in nutrition are unknown. They seem very important in development, being abundant in the food and formed largely in the system in early life.2 They certainly do not enter into the composition of the tissues ; and it would seem that they must be important in the two remaining phenomena of nutrition, namely, the formation of fat and the development of animal heat. The relations of sugar to these two processes will be taken up under their appropriate heads. The fats taken as food are either consumed in the organ- ism, or are deposited in the form of adipose tissue. That the fats are consumed, there can be no doubt ; for, in the normal alimentation of man, fat is a constant article, and it is never discharged from the body. We are forced to admit, however, that the changes which fat undergoes in its process of destruction are not thoroughly understood. All that we positively know is, that the fatty principles of the food are formed into a fine emulsion in the small in- testine, and are taken up, chiefly by the lacteals, and dis- charged into the venous system. For a time, during ab- 1 We have already noted the exceptional discharge of sugar, fat, and nitro- genized matter in the milk. 2 We have already noted these facts, as well as the production of glyco- genic matter and sugar in animals deprived entirely of starch and sugar in their food, when it seems that the formation must take place from the albuminoid principles. NON-NITKOGKSTZED PRINCIPLES. 381 sorption, fat may exist in certain quantity in the blood; but it soon disappears, and is either destroyed directly in the circulatory system, or is deposited in the form of adipose tissue to supply a certain amount of this substance con- sumed. That it may be destroyed directly is proven by the consumption of fat in instances where the amount of adipose matter is insignificant ; and that the adipose tissue of the organism may be consumed is shown by its rapid disappear- ance in starvation. The question of the relations of fat to nutrition is im- portant, but somewhat obscure. It does not take part in the nutrition of. the parts that are endowed, to an eminent de- gree, with the so-called vital functions; and when these tissues are brought to their highest point of functional de- velopment, the fat is entirely removed from their substance. If fat be not a plastic material, it would seem to have no func- tion remaining but that of keeping up, by its oxidation, the animal temperature. But it is not proven that fat, or fat and sugar, are the sole principles concerned in the production of carbonic acid and the generation of heat ; for both of these phenomena occur in the carnivora, and in man, when fat and sugar are eliminated from the food and the fat in the body has been reduced to the minimum. Fat is undoubtedly destroyed in the organism, and probably assists in the formation of the carbonic acid eliminated; it is also taken in much larger proportion in cold than in temperate or warm, climates;1 but we cannot, with our present information, say without reserve, that fats and sugar are oxidized directly, by a pro- cess with which we are familiar under the name of com- bustion, and that their exclusive function is the production of animal heat. It is a curious fact that fat is generally deposited in tissues during their retrograde processes. The muscular fibres of the uterus, during the involution of this organ after partu- rition, become the seat of a deposit of fatty granulations. 1 See vol. ii., Alimentation, p. 128. 382 NUTRITION. Long disuse of any part will produce such changes in its power of appropriating nitrogenized matter for its regenera- tion, that it soon becomes atrophied and altered. Instead of the normal nitrogenized elements of the tissue, we have, under these circumstances, a deposition of fatty matter. The fat is here inert, and takes the place of the substance that gives to the part its characteristic function. These phe- nomena are strikingly apparent in muscles that have been long disused or paralyzed, or in nerves that have lost their functional activity. If the change be not too extensive, the fat may be made to disappear, and the part will return to its normal constitution, by appropriate exercise ; but frequently the alteration has proceeded so far as to be irremediable and permanent. This condition is known in pathology under the name of fatty degeneration — a term which implies that the nitrogenized elements of the part are changed or degen- erated into fat, and which is not strictly correct. During the ordinary process of nutrition, the nitrogenized elements are removed by disassimilation, and new matter, of the same kind, is deposited ; but when the so-called fatty degenera- tion ocures, fat is substituted for the nitrogenized substance. This change, then, should rather be called fatty substitution.1 Accurate observations have shown that, in young ani- mals, rapidly fattened, all the adipose matter in the body cannot be accounted for by what is taken in as food ; and it is certain that fat may be produced de novo in the organism. Formation and Deposition of Fat. — The question of the generation of fat in the economy is one of great importance. Whatever the exact nature of the changes accompanying the destruction of non-nitrogenized matter may be, it is certain that the fat stored up in the body is consumed, when there is a deficiency in any of the elements of food, as well as that which is taken into the alimentary canal. It is 1 LITTRK ET ROBIN, Dictionnaire de medecine, Paris, 1865, p. 1444, Article, Substitution graisseusc. FORMATION AND DEPOSITION OF FAT. 383 rendered probable, indeed, by the few experiments that have been made on the subject, that obesity increases the power of resistance to inanition.1 At all events, in starvation, the fatty constituents of the body are the first to be consumed, and they almost entirely disappear before death. As we have already seen, sugar is never deposited in any part of the organism, and is only a temporary constituent of the blood. If the sugars and fats have, in certain regards', simi- lar functions in nutrition, and if, in addition to the mechani- cal functions of fat, it may be retained in the organism for use under extraordinary conditions, it becomes very impor- tant to ascertain the mechanism of its production and depo- sition. The production of fatty matter by certain insects, in ex- cess of the fat supplied with the food, was established long ago by the researches of Huber, whose experiments were fully confirmed by Dumas and Milne-Edwards.3 A little later, similar observations were made upon birds, by Persoz,8 and upon birds and mammals, by Boussingault.4 Some of the experiments of Boussingault are peculiarly interesting, as they were made upon pigs, in which the digestive appa- ratus closely resembles that of the human subject. They showed conclusively that, under certain circumstances, more fat exists in the bodies of animals than can be accounted for by the total amount of fat taken as food added to the fat ex- isting at birth. In some very interesting experiments with relation to the influence of different kinds of food upon the development of fat, it was ascertained that fat could be pro- duced in animals upon a regimen, sufficiently nitrogenized, but deprived of fatty matters ; but the fact should be recog- 1 See vol. ii., Alimentation, p. 26. 8 MILNE-EDWARDS, Lemons sur la physiologic., Paris, 1862, tome vii., p. 653. 3 PERSOZ, Experiences sur Fengrais des oies. — Comptes rendus, Paris, 1844, tome xviii., p. 245. 4 BOUSSINGAULT, Reckerches experimentales sur le developpement de la. graissi pendent V alimentation des animaux. — Memoire* de chimie agricole ct de physiologic, Paris, 1854, p. 105, et seq. 384 NUTRITION. nized " that the nutriment which produces the most rapid and pronounced fattening is precisely that which joins to the proper proportion of albuminoid substances the greatest pro- portion of fatty principles." Animals cannot be fattened without a certain variety in the regimen. We have already discussed the necessity of a varied diet, and have shown that an animal will die of star- vation when confined exclusively to one class of principles, even if this be of the most nutritious character ; a and it is not necessary to refer again to the experiments which have demonstrated that a diet confined exclusively to starch, sugar, or fat, or even pure albumen or fibrin, cannot sus- tain life, much less fatten an animal. We are prepared, then, to understand why, in the pigs experimented upon by Boussingault, a regimen confined to potatoes did not prove to be fattening, notwithstanding the large proportion of starch,3 and that fat was produced in abundance only when the food presented the proper variety of principles. Yery little is known concerning the precise mechanism of the production of fat. The experiments of Boussingault seem to leave no doubt that it may be formed from any kind of food, even when it is exclusively nitrogenized ; 4 but it is, nevertheless, a matter of common observation that certain articles of diet are more favorable to its deposition than others ; and it is also true that the herbivora are fattened much more readily, as a rule, than the carnivora. Theoretical considerations would immediately point to starch and sugar as the elements of food most easily con- vertible into fat, as they contain the same elements, though in different proportions ; and it is more than probable that 1 BOUSSINGAULT, op. cit., p. 16Y. 2 See vol. ii., Alimentation, p. 128. 3 Op. cit., p. 122. 4 The researches of Wurtz have shown that certain of the albuminoid prin- ciples can be converted into fatty acids by the action of an alkali and heat, and that this may also occur spontaneously (WURTZ, Sur la transformation de la fibrine en acide butyrlque. — Comptes rendus, Paris, 1844, tome xviii., p. 704). FORMATION AND DEPOSITION OF FAT. 385 this view is correct. It is said that in sugar-growing sec- tions, during the period of grinding the cane, the laborers become excessively fat, from eating large quantities of the saccharine matter. We cannot refer to any exact scientific observations on this point, but the fact is pretty generally admitted by physiologists. Again, it has been frequently a matter of individual experience that sugar and starch are favorable to the deposition of fat, especially when there is a constitutional tendency to obesity. A most remarkable ex- ample of this, and one which has met with considerable notoriety, is worthy of mention, though not reported by a scientific observer. We refer to the letter on corpulence, by Mr. Banting.1 The writer of this curious pamphlet, in 1862, was sixty-six years old, five feet and five inches in height, an,d weighed two hundred and two pounds. Under the ad- vice of Mr. William Harvey, F. R. C. S., of London, he con- fined himself to a diet containing no sugar, and as little starch and fat as possible. Continuing this regimen for one year, he gradually lost weight, at the rate of about one pound each week, until he was reduced to one hundred and fifty-six pounds. At the time the last edition of the pam- phlet was published, in 1864, he enjoyed perfect health and weighed one hundred and fifty pounds, his weight varying only to the extent of one pound, more or less, in the course of a month. This little tract is very interesting, both from the importance of its physiological relations and its quaint literary style. It has had an immense circulation, and many persons suffering from excessive adipose development have adopted the system here advised, with results more or less favorable. A study of the course of diet here prescribed shows it be a pretty rigid training system, with the excep- tion of succulent vegetables and liquids, which are allowed without restriction. It is proper to remark, however, that some enthusiastic advocates of the plan have exceeded the limits prescribed, and neglected the caution of the author 1 BANTING, Letter on Corpulence, London, 1864. 25 386 NUTRITION. always to employ it under the advice of a physician ; and its too rigid enforcement has been followed by serious dis- turbances in general nutrition. Others, however, have veri- fied the favorable results obtained by Mr. Banting. It is difficult to explain the remarkable constitutional tendency to obesity observed in some individuals, which is very often hereditary. Such persons will become very fat upon a comparatively low diet, while others deposit but lit- tle adipose matter, even when the regimen is abundant. It is to be noted, however, that the former are generally ad- dicted to the use of starchy, saccharine, and fatty elements of food, while the latter consume a greater proportion of nitrogenized matter. It is not an uncommon remark that the habit of taking large quantities of liquids favors the formation of fat ; but it is not easy to find any scientific basis for such an opinion. As to the formation of fat by any particular organ or organs in the body, no positive scientific view has been advanced, except the proposition by Bernard, that the liver had this function, in addition to its glycogenic office. This we have already discussed, and have shown that such a function is far from being positively established.1 Condition under which Fat exists in the Organism. — It is said that fat combined with phosphorus is united with ni- trogenized matter in the substance of the nervous tissue ; but its condition here is not well understood, as we shall see when we come to treat of the nervous system. A small quantity of fat is contained in the blood-corpuscles, and a little is held in solution in the bile ; but with these exceptions, fat always exists in the body isolated and uncombined with nitrogen- ized matter, in the form of granules or globules and of adipose tissue. The three varieties of fat are here combined in variable proportions, which is the cause of the differences in its consistence in different situations. The ultimate ele- 1 See page 328. ANATOMY OF ADIPOSE TISSUE. 387 ments of fat are, carbon, hydrogen, and oxygen, the two latter in unequal proportions. It has been found very diffi- cult, however, to obtain either stearin e, margarine, or oleine in a condition of sufficient purity to ascertain their exact ultimate composition.1 Physiological Anatomy of Adipose Tissue. — Adipose tissue is found in abundance in the interstices of the sub- cutaneous areolar tissue, where it is sometimes known as the panniculus adiposus. It is not, however, to be confounded with the so-called cellular or areolar tissue, and is simply associated with it without being one of its essential parts ; for the areolar tissue is abundant in certain situations, as the eyelids and scrotum, where there is no adipose matter, and adipose tissue exists sometimes, as- in the marrow of the bones, without any areolar tissue. Adipose tissue is widely distributed in the body, and has important mechanical functions.2 Its anatomical element is a vesicle, from -g-i-g- to -g-fj of an inch in diameter, composed of a delicate, structureless membrane, 2g^00 of an inch thick, enclosing fluid contents.3 The form of the vesicles is naturally rounded or ovoid ; but in microscopical prepara- tions they are generally compressed so as to become irregu- larly polyhedrical. The membrane sometimes presents a small nucleus attached to its inner surface. The contents are a minute quantity of an albuminoid fluid moistening the internal surface of the membrane, and a mixture of oleine, margarine, and stearine, liquid at the temperature of the body, but becoming harder on cooling.* Little rosettes formed of acicular crystals of margarine are frequently ob- served in the fat- vesicles, when the temperature is rather low. 1 ROBIN* ET VERDEIL, Traite de chimie anatomique et phwiologique, Paris, 1853, tome iii., p. 105. 2 See vol. i., Introduction, p. 65. 3 LITTRE ET ROBIN*, Didionnaire de medecine, Paris, 1865, Article, Adipeiix. 4 TODD AND BOWMAN, Physiological Anatomy and Physiology of Man, Phila- delphia, 1857, p. 89. 388 NUTRITION. The adipose vesicles are collected into little lobules, from -£% to J of an inch in diameter,1 which are surrounded by a rather wide net-work of capillary blood-vessels. Close ex- amination of these vessels shows that they frequently sur- round individual fat-cells, in the form of single loops. There is no distribution of nerves or lymphatics to the ele- ments of adipose tissue. It is seen by this sketch of the structure of adipose tis- sue, that there is no anatomical reason for classing these vesicles with the ductless glands, as is done by some physi- ologists. They undoubtedly, under certain conditions, have the power of filling themselves with fat ; but it would be no more appropriate to call this a secretion than to apply this term to the development and nutrition of the muscular sub- stance within the sarcolemma. Conditions which influence Nutrition. — We know more concerning the conditions that influence the general pro- cess of nutrition than about the nature of -the process itself. It will be seen, for example, when we come to study the ner- vous system, that there are nerves which regulate, to a certain extent, the nutritive forces. We do not mean to imply that nutrition is effected through the influence of the nerves, but it is the fact that certain nerves, by regulating the supply of blood, and perhaps by other influences, are capable of modifying the nutrition of parts to a very consid- erable extent. In discussing the influence of exercise upon the develop- ment of parts, we have shown that this is not only desirable but indispensable ; and the proper performance of the func- tions of all parts involves the action of the nervous system. It is true that the separate parts of the organism and the organism as a whole have a limited existence ; but it is not true that the change of nitrogenized, living substance into effete matter, a process that is increased in activity by phys- 1 LITTRE ET ROBIN, loc. cit. CONDITIONS WHICH INFLUENCE NUTK1T1ON. 389 iological exercise, consumes, so to speak, a definite amount of the limited life of the part. Physiological exercise increases disassimilation, but it also increases the activity of nutrition and favors development. It is a favorite sophism to assert that bodily or mental effort is made always at the expense of a definite amount of vitality and matter consumed. This is partly true, but mainly false. Work involves change into effete matter ; but when restricted within physiological limits, it engenders a corresponding activity of nutrition, assuming, of course, that the supply from without be suffi- cient, Other things being equal, a man will live longer under a system of physiological exercise of every part, than if he made the least effort possible. It is, indeed, only by such use of parts that they can undergo proper development and become the seat of normal nutrition. But notwith- standing all these facts, life is self-limited. Unless subjected to some process which arrests all changes, such as cold, the action of preservative fluids, etc., organic substances are con- stantly undergoing transformation. In the living body, their disassimilation and nutrition are unceasing ; and after they are removed from the influence of what is called life, they change, first losing irritability, or becoming incapable of performing their functions, and afterward decomposing into matters which, like the results of their disassimilation, are destined to be appropriated by the vegetable kingdom. Nutrition sufficient to supply the physiological decay of parts cannot continue indefinitely. The wonderful forces in the fecundated ovum lead it through a process of develop- ment that requires, in the human subject, more than twenty years for its completion ; and when development ceases, no one can say why it becomes arrested, nor can we give any sufficient reason why, with a sufficient and appropriate sup- ply of material, a man should not grow indefinitely. After the being is fully developed, and during what is known as the adult period, the supply seems to be about equal to the waste. But after this, nutrition gradually becomes deficient, 390 NUTRITION. and the deposition of new matter in progressive old age is more and more inadequate to supply the place of the living nitrogenized substance. We may at this time, as an excep- tion, have a considerable deposition of fat, but the nitrogen- ized matter is always deficient, and the proportion of inert inorganic matter combined with it is increased. There can be little if any doubt that the forces which induce the regeneration or nutrition of parts reside in the organic nitrogenized substance, and that they give to the parts their characteristic functions, which we call vital ; the inorganic matter being passive, or having, at the most, purely physical functions. If, therefore, as age advances, the organic matter be gradually losing the power of com- pletely regenerating its substance, and if its proportion be progressively diminishing, while the inorganic matter is increasing in quantity, a time will come when some of the organs necessary to life will be unable to perform their office. When this occurs we have death from old age, or physiological dissolution. This may be a gradual failure of the general process of nutrition, or it may attack some one organ or system. Why death is thus certain to occur, we do not know, any more than we can explain why and how animals live. The modifications in nutrition due to the very varied in- fluences that may be brought to bear upon it present a most extended subject for discussion ; but we shall not touch upon any of these influences that are not purely physiological. Among the most interesting of these modifications, are those due to age, constituting, as they do, in early life, the process of development. They will be treated of fully in connection with the subject of generation. It is evident, also, from what we have already said, that each tissue and organ has its own conditions of nutrition and development ; and this constitutes another interesting division of the subject, the more so, because the nutrition and development of the indi- vidual tissues are closely connected with the processes of PRODUCTS OF DISASSIMILATTON. 391 regeneration and repair after injury. We have stated, as far as possible, all that is positively known of the nutrition of the fully-formed tissues of the body ; but their develop- ment belongs to embryology. If we were to attempt to follow the processes of regeneration after injury in nerves, muscles, bone, etc., we would be compelled to pass almost immediately into the domain of pathology. The influences of climate, respiratory activity, food, etc., have already been considered under the heads of respiration, alimentation, and excretion, and will be touched upon again in connection with animal heat. Products of Disassimilation. — It only remains now to recapitulate briefly the mode of production of the excretions. The process of disassimilation, we are aware, always accom- panies nutrition, and the substances thus formed are the result of the final changes of the organic constituents of the tissues. As we have seen in studying the urine, the excre- mentitious principles proper are always associated with in- organic matter, which has passed through the organism ; and while there are many effete substances that we have been able to recognize, there are probably others which have thus far escaped observation. It is almost futile to specu- late upon the probable bearing which the discovery of new excrementitious principles will have upon pathological con- ditions, while there are so many, which we now know only by name, their relations to the different tissues being still obscure ; but if we reason from the light thrown upon cer- tain diseased conditions by the fact that urea, the urates, and cholesterine are liable to be retained in the blood and produce certain symptoms, we may safely infer that the description of new effete principles will have an important influence upon our pathological knowledge as well as our comprehension of physiological processes. The following are the most impor- tant excrementitious matters, the relations of which to nutri- tion and disassimilation are more or less fully understood : 392 NUTRITION. Products of Disassimilation. Name of principle. How excreted. f Principally by the lungs ; but also Carbonic acid (C02) ................................ •< by the skin, and in solution in the [ excreted fluids. Alkaline sudorates (Sudoric acid, CioH8Oi3N) ........... Perspiration. f Principally in the urea(c2H4N2o2).. . tain quantity in I the perspiration. Urate of soda (Uric acid, C6HIST202+HO) ................. Urine. Urate of ammonia Urate of potassa Urate of lime Urate of magnesia Hippurate of soda (Hippuric acid, Ci8H8N06) Hippurate of potassa Hippurate of lime Creatine (C8H904N3+ 2HO) ............................ " Creatinine (C8H702N3) ................................. " Oxalate of lime (CaO,C203+2HO) ....................... " Xanthine (C10H6N404) ................................. " Stercorine (changed from Cholesterine, C25II220, of bile). . . Faeces. Excretine (C78H7802S) ................................. " In the above list we have omitted all doubtful excremen- titious principles, as well as the inorganic compounds found in the excreted fluids ; and we can safely assume that the substances therein enumerated represent, as far as we are now able to determine, the physiological wear of the organ- ism. We shall not again discuss the fact that the life of tissues involves physiological waste or decay, and that the excrementitious principles proper represent the final changes of the organic substance. We know that this process goes on without necessarily involving exercise of the peculiar functions of the parts ; but it is no less true that exercise, or work, increases the activity both of nutrition and wear. This is one of the great principles underlying all our ideas PRODUCTS OF DISASSIMILATION. 393 of the process of nutrition. We shall not discuss here the influence of work upon the elimination of some of the nitro- genized compounds, particularly urea, for we have already examined that subject most carefully in another place ; x but we have no hesitation in stating, as a general law, that has yet to find its exceptions, that physiological work increases excretion. 1 See page 226. CHAPTER XIII. ANIMAL HEAT. General considerations — Limits of variation in the normal temperature in man — Variations with external temperature — Variations in different parts of the body — Variations at different periods of life — Diurnal variations — Rela- tions of animal heat to digestion — Influence of defective nutrition and in- anition— Influence of exercise, mental exertion, and the nervous system, upon the heat of the body. THE process of nutrition in animals is always attended with the development of heat, and produces a temperature more or less independent of external conditions. This is true in the lowest as well as the highest animal organizations ; and analogous phenomena have even been observed in plants. In cold-blooded animals, nutrition may be suspended by a diminished external temperature, and certain of the functions become temporarily arrested, to be resumed when the animal is exposed to a greater heat. This is true, to some extent, in certain warm-blooded animals that periodically pass into a condition of stupor, called hibernation ; but in man, and nearly all the warm-blooded animals, the general tempera- ture of the body can undergo but slight variations. The animal heat is essentially the same in the intense cold of the frigid zones and under the burning sun of the tropics ; and if, from any cause, the body become incapable of keeping up its temperature when exposed to cold, or moderating it when exposed to heat, death is the invariable result. The production of animal heat is so closely connected with nutrition, that in serious pathological modifications of ANIMAL HEAT. 395 this process, as in the essential fevers or extensive inflamma- tions, the temperature of the body becomes an important guide, particularly in prognosis. The clinical value of a recognition of the temperature in disease has only been fully appreciated within a few years, especially since the very elaborate observations of Wunderlich, and other German observers.1 The study of the temperature in different classes of ani- mals presents very great interest, but the limits of a work on pure human physiology restrict us to the phenomena as observed in man, and in animals in which the processes of nutrition are similar, if not identical. We shall therefore treat of the subject from one point of view, and consider it as follows : 1. The normal temperature in the human subject, with its variations in different parts of the body and at different periods of life. 2. The diurnal variations in the animal temperature, and the relations of alimentation, digestion, respiration, nutri- tion, exercise, and the nervous system. 3. The means by which the temperature of the body is kept within the limits necessary to the preservation of life and health. Limits of Variation in the Normal Temperature in jlfan. — A great number of observations have been made upon the normal temperature in the human subject under different conditions ; but we shall cite those only in which all sources of error in thermoinetry seem to have been avoided, and in which the results present noticeable peculiarities. One of the most common methods of taking the general tem- perature has been to introduce a delicate thermometer, care- fully protected from all disturbing conditions, into the axilla, reading off the degrees after the mercury has become abso- 1 HIRTZ, Chaleur dans Fetal de maladie. — Nouveau dictionnaire de medecine, Paris, 1867, tome vi., p. 772, et seq. 396 NUTRITION. lutely stationary. Nearly all observations made in this way agree with the results obtained by Gavarret,1 who estimates that the temperature in the axilla, in a perfectly healthy adult man, in a temperate climate, ranges between 97*7° and 99*5°.a Dr. Davy, from a large number of observa- tions on the temperature under the tongue, estimates the standard, in a temperate climate, at 98°. 3 When we ex- amine the temperature of the blood in the deeper vessels and the variations in different parts, we shall see that the axilla and the tongue, being more or less exposed to external influences, do not exactly represent the general heat of the organism ; but these are the situations, particularly the axilla, in which the temperature is most frequently taken, both in physiological and pathological examinations. As a standard for comparison, we may assume that the most common tem- perature in these situations is 98°, subject to variation within the limits of health of about 0*5° below and 1*5° above. Variations with External Temperature. — There can be no doubt that the general temperature of the body varies, though within very restricted limits, with extreme changes in climate. The results obtained by Davy, in a large num- ber of observations in temperate and hot climates, show an elevation in the tropics of from 0*5° to 3°.4 It is well known, also, that the human body, the surface being properly pro- tected, is capable of enduring for some minutes a heat much greater than that of boiling water. Under these conditions, the general temperature is raised but very slightly, as com- pared with the intense heat of the surrounding atmosphere. According to the observations of Dr. Dobson, the tempera- ture was only raised to 99*5° in one instance, 101*5° in an- 1 GAVARRET, De la chaleur produite par Us etres vivants, Paris, 1855, p. 100. 2 All the temperatures, unless it be otherwise stated, are given according to the Fahrenheit scale. 3 DAVY, Researches, Physiological and Anatomical, London, 1839, vol. i., p. 196. 4 DAVY, loc. tit. HEAT. 397 other, and 102° in a third, when the body was exposed to a heat of more than 2120.1 MM. Delaroche and Berger, how- ever, found that the temperature in the mouth could be in- creased by from 3° to 9°, after sixteen minutes' exposure to intense heat.3 This was for the external parts only ; but it is not at all probable that the temperature of the internal organs ever undergoes such extensive variations. It is very difficult to estimate the temperature in persons exposed to intense cold, as in Arctic explorations, because the greatest care is always taken to protect the surface of the body as fully as possible ; but experiments have shown that the animal heat may be considerably reduced, as a tempo- rary condition, without producing death. In the. latter part of the last century, Dr. Currie caused the temperature in a man to fall 15° by immersion in a cold bath; but he could not bring it below 83°. This extreme depression, however, lasted only two or three minutes, and the tem- perature afterward returned to within a few degrees of the normal standard.3 Nearly the same results were ob- tained by Hunter, in a series of experiments on a mouse. With an external temperature of 60°, he found the tempera- ture in the upper part of the abdomen 99°, and in the pelvis • 96°. The animal was then exposed for an hour to a cold 1 DOBSON, Experiments in an Heated Room. — Philosophical Transactions, Lon- don, 1775, p. 463, et seq. 2 DELAROCHE, Experiences sur les effets qu'une forte chaleur produit dans Tecono- mie animale. — Theses de Paris, 1806, tome i., No. xi. M. Delaroche, in connec- tion with M. Berger, made a number of very interesting experiments upon the influence of high temperatures upon the general heat of the body. Delaroche remained for eight minutes exposed to a temperature of 176°, and the tempera- ture under the tongue was raised from a little over 98° to nearly 107°. In an experiment of the same kind by Berger, the temperature was raised, in sixteen minutes, from 98° to nearly 105°. Enclosed in a hot steam-bath of from 100° to 120°, the temperature, in one instance, was raised, in thirteen minutes, to over 103°, and in another, in fifteen minutes, to 101° (Loc. cit., pp. 43, 44). 3 CURRIE, An Account of the remarkable Effects of a Shipwreck on the Mari- ners ; with Experiments and Observations on the Influence of Immersion in fresh and salt Water, hot and cold, on the Powers of the living Body. — Philosophical transactions, London, 1792, p. 204, et seq. 398 NUTEITION. atmosphere of 13°, and there was a diminution of the tem- perature at the diaphragm of 16°, and at the pelvis of 180.1 These results show that while the normal variations in temperature in the human subject, even when exposed to great climatic changes, are very slight, generally not ranging beyond two degrees, the body may be exposed for a time to excessive heat or cold, and the extreme limits, consistent with the preservation of life, may be reached. As far as lias been ascertained by direct experiment, these limits are 83° and 107° ; giving a range of about 15° below and 9° above the average standard under normal conditions.2 Variations in different Parts of the Body. — It is to be expected that the temperature of the internal organs should be higher and more constant than that of parts, like the axilla or mouth, more or less exposed to loss of heat by evaporation and contact with the cool air ; and the differences observed in the blood in certain parts, as in the two sides of the heart, have important bearings, as we shall hereafter show, upon the various theories of animal heat. We shall here simply note the variations observed in the blood in different situa- tions, and confine ourselves chiefly to late observations, which have generally been made with apparatus much more reliable and delicate than was formerly employed. A great number of experiments have been made upon modifications in temperature accompanying the general change of the blood from arterial to venous ; but perhaps the most exact and elaborate are those by M. Claude Ber- nard. For measuring the temperature in different parts of the vascular system, he used the exceedingly delicate " me- 1 HUNTER, Observations on certain Parts of the Animal (Economy, London, 1792, p. 114. 2 We have referred only to observations upon the influence of the surround- ing temperature in man and mammals generally. Certain important peculiari- ties in this regard have been observed in hibernating animals, and in reptiles, fishes, and insects, the consideration of which belongs to comparative physi- ology. ANIMAL HEAT. 399 tastatic " thermometers of M. "Walferdin ; 1 and in all com- parative observations lie employed the same instrument, in- troduced successively into different parts, frequently revers- ing the order, and employing every precaution so as to insure perfectly physiological conditions. The preeminent skill of this distinguished observer in experimenting upon living ani- mals is almost in itself a sufficient guarantee of the accuracy of his results. It is universally admitted that the blood becomes slightly lowered in its temperature in passing through the general capillary circulation ; 3 but the amount of difference is ordi- narily not more than a fraction of a degree, and is dependent, in all probability, upon external conditions and the evapora- tion constantly going on from the surface of the body. This fact is not at all opposed to the proposition that the animal heat is generated in greatest part in the general capillary system, as one of the results of nutritive action ; for the blood circu- lates with such rapidity that the heat acquired in the capil- laries of the internal organs, where little or none is lost, is but slightly diminished before the fluid passes into the arte- ries, even in circulating through the lungs ; and the evapora- tion from the surface simply moderates the heat acquired in the tissues, and keeps it at the proper standard. We know that the heat of the body is equalized by means of the circu- lation and cutaneous transpiration ; and all comparative ob- servations on the temperature in different parts show that, where it is not subjected to refrigerating influences, the blood is warmer in the veins than in the arteries. The elaborate investigations of Bernard have demon- strated that the blood is, as the rule, from 0'36° to 1-8° warmer in the hepatic veins than in the aorta. The tem- perature in the hepatic veins is from 0*18° to 1*44° higher 1 BERNARD, Liquides de Forganisme, Paris, 1859, tome i., p. 67, et seq. Ber- nard here gives a full description of this instrument. With it he has been able to note accurately variations of ^ of a degree cent. 8 BERNARD, op. cit., p. 58, and LOXGET, Traite de phyeioloffie, Paris, 1869, tome ii., p. 517. 400 NUTRITION: than in the portal veins. These figures are the result of numerous experiments made on dogs. The maximum of thirty-three observations upon the temperature in the aorta was 105*8°, and the minimum, 98*78° ; the maximum of thirty-two observations upon the portal vein was 106*34r°, and the minimum, 100*04° ; the maximum of thirty-five ob- servations upon the hepatic veins was 107°, and the mini- mum, 99*86V Compared with the aorta, the temperature of the portal vein was generally found to be higher (maxi- mum of differencej 0*9°) ; but in a few instances, five out of fifteen, it was a very little lower, which is explained by Ber- nard by the supposition that the intestinal canal is not en- tirely removed from external modifying influences. These results show that the blood coming from the liver is warmer than in any other part of the body. The general fact that the superficial parts are cooler than those less exposed to loss of heat by evaporation, observed by Hunter,3 Davy,8 and others, does not demand extended discussion ; but in a series of experiments by Breschet and Becquerel,4 who were among the first to employ thermo- electric apparatus in the study of animal heat, it was found that the cellular tissue was from 2*5° to 3*3° cooler than the muscles. This difference will be readily understood when we consider the production of heat in the general system, and more especially in the highly-organized parts. A most interesting question, in this connection, relates 1 BERNARD, op. cit., p. 84. We have calculated these results from an elabo- rate table given by Bernard, but have disregarded two observations (Nos. 17 and 18, table in.), made on animals after death, the circulation being kept up by artificial respiration. 2 HUNTER, Experiments and Observations on Animals, with respect to the Power of producing Heat. — Observations on certain Parts of the Animal (Economy ', Lon- don, 1792, pp. 108, 115. 3 DATY, Researches, Physiological and Anatomical, London, 1839, vol. i., p. 150, et seq. The paper here referred to first appeared in the Philosophical Transactions, in 1814. 4 BRESCHET ET BECQUEREL, Premier memoire sur la chaleur animate. — Annales de chimie et de physique, Paris, 1835, tome lix., p. 129. ANIMAL HEAT. 401 to the comparative temperature of the blood in the two sides of the heart. Upon this point there have been several conflicting observations, the results favoring two opposite theories of calorification. By some it has been thought that the blood gains heat in passing through the lungs, and this is explained by the theory of the direct union, in these organs, of oxygen with the hydro-carbons ; while others suppose that the blood is slightly refrigerated in the air-cells. The ques- tions here involved will be fully discussed in connection with the theories of animal heat ; and we shall confine ourselves at present to a study of the experimental facts. An excellent review of all the important direct observa- tions upon the temperature of the two sides of the heart in living animals is given by Bernard, as an introduction to his original experiments. It appears from this that Golem an, Astley Cooper, Saissy, Davy, Thackrah, and Nasse, found the blood warmer in the left side of the heart than in the right. Mayer did not find any difference in animals re- cently killed. Autenreith found the blood warmer in the right side in an animal recently killed, the circulation being kept up by artificial respiration. Berger, Collard de Mar- tigny, Magendie and Bernard, Hering, Georg von Liebig, and Fick found a marked difference in favor of the right side.1 This being the state of the question in 1859, it re- mains to see how far the conditions under which these re- sults were obtained are capable of explaining their contra- dictory character. It is evident that, when the chest is opened, the external refrigerating influences might act differently upon the two sides of the heart, particularly as the right ventricle is much thinner than the left. It would not be improper, indeed, to exclude all observations made in this way, and depend en- tirely upon experiments in which the physiological condi- tions are not so palpably violated. Magendie and Bernard introduced delicate thermometers into the two sides of the 1 BERNARD, Liquides de Vorganisme, Paris, 1859, tome i., p. 55, el seq. 402 NUTRITION. heart, through the vessels in the neck, without opening the chest. These experiments were made upon a horse, and the right heart was always found considerably warmer than the left. Hering introduced a thermometer into the cavities of the heart in a living calf affected with cardiac ectopia. The temperature of the right side was 102'74°, and the left side, IGI'790.1 Georg von Liebig illustrated one of the sources of error in all examinations made after opening the chest, by filling the cavities of the heart of a dog with warm water, placing the organ in a water-bath, and bringing the two sides to precisely the same temperature. After five minutes' exposure to the air, the temperature in the right ventricle was sensibly lower than in the left, which was un- doubtedly due to the difference in the thickness of the walls.3 The observations by Bernard himself upon dogs and sheep are very conclusive, as far as these animals are concerned. In dogs he found a difference of from 0*1° to 0*2°, always in favor of the right side ; and the results in sheep were nearly the same.3 A series of experiments recently instituted by Colin shows pretty conclusively that there are other conditions that may account, in a measure, for the opposite results of observations on the temperature of the two sides of the heart, besides exposure of the parts to the air. In one hun- dred and two experiments, he found the blood warmer in the right side in thirty-one ; in fifty-one, it was warmer on the left side ; and in twenty-one, there was no difference.4 He finds that in animals covered with a thick fleece, like sheep, where there is but little loss of temperature by the general surface, the blood in the right heart is generally 1 BERNARD (op. cit., p. 106, et seq.) gives a full account of this very interest- ing observation. 2 BERNARD, op. cit., p. 65. 3 Op. cit., pp. 11Q, 116. 4 COLIN, Experiences sur la chaleur animale, in the report by LONGET. — Comp- tcs rendus, Paris, 1867, tome Ixiv., p. 464. The error in the figures quoted is in the original report. . AKIMAL HEAT. 4:03 warmer than in the left ; while in horses, dogs, and probably in man, where there is considerable loss of heat by the skin, the blood is warmer on the left side. It is difficult to ex- plain how the blood can pass through the lungs without losing a certain amount of heat, but the experiments just detailed, taken in connection with some of the earlier ob- servations, leave little doubt as to the fact. These experiments are only indirectly applicable to the human subject ; and if it be proven that in animals, the con- ditions vary with " the state of the skin, the digestive appa- ratus, and the muscular system," * it is impossible, in the absence of positive demonstration, to say what change in temperature, if any, takes place in the blood in its passage through the lungs. The only reliable observations upon this point in man are those lately made by Prof. Lombard, of Boston. Prof. Lombard used in his experiments a very ingenious and delicate thermo-electric apparatus, capable of indicating a difference of -^-^ of a degree cent.8 With this instrument, he was able to determine very slight variations in the temperature of the blood in the arterial system, by simply placing the conductors over any of the superficial vessels, like the radial. Of course it is impossible to note the actual temperature in the two sides of the heart in the human subject during life ; but Prof. Lombard en- deavored to arrive at the same end, by calculating that if all the sources of refrigeration in the lungs were artificially removed, the blood in the arteries should gain about the same amount of heat that would be lost under ordinary con- ditions. To effect this object, he breathed air saturated with moisture and of the same temperature as the circulating blood. " If, then, when respiration takes place under ordi- nary circumstances, the blood is cooled one-third of a degree (cent.) in passing through the lungs, the temperature should 1 COLIN, loc. tit. 2 LOMBARD, Description d'un nouvel appareil thermo-electrique pour P etude de la chaleur animale. — Archives de physiologic, Paris, 1868, tome i., p. 498. 404 NUTRITION. be raised so much ; that is to say, one-third of a degree, when we respire air at the temperature of the blood and saturated with the vapor of water, all loss of heat then being impossible." l In numerous experiments performed on this principle, Prof. Lombard failed to observe a sufficiently marked elevation of temperature to justify the conclusion that the blood is ordinarily cooled in passing through the lungs. These experiments cannot be so positive as those made by introducing thermometers into the heart in living animals without opening the chest or disturbing the circu- lation ; but they are important, in connection with such observations, as failing to prove that the blood is either cooled or heated in the lungs. From these facts it appears that there is no positive evi- dence of any change in the temperature in the blood in pass- ing through the lungs in the human subject. In animals there probably exist no constant differences in temperature in the two sides of the heart. "When the loss of heat by the gen- eral surface is active, as in animals with a slight covering of hair, the blood is generally cooler in the right cavities ; but in animals with a thick covering, that probably lose a great deal of heat by the pulmonary surface, the blood is cooler on the left side. There can be no doubt that there are refri- gerating influences in the lungs, both from the low tempera- ture of the inspired air and evaporation ; but these are equalized and sometimes overcome by processes in the blood itself; although, as we shall see hereafter, the lungs are by no means the most important organs of calorification. Variations at different Periods of Life. — The most im- portant variations in the temperature of the body at different periods of life are observed in infants just after birth. Aside from one or two observations, which are admitted to be ex- 1 LOMBARD, RechercJm experimentales sur V influence de la respiration sur la temperature du sang dans son passage d travers le poumon. — Archives de physi' ologie, Paris, 1869, tome ii., p. 7. ANIMAL HEAT. 405 ceptional, the body of the infant and of young mammalia and birds, removed from the mother, presents a diminution in temperature of from one to nearly four degrees. This important fact was established by "W. F. Edwards,1 who made, also, a number of curious and instructive experiments upon the power of young warm-blooded animals to resist cold. In infancy the ability to resist cold is less than in later years ; but after a few days the temperature of the child nearly reaches the standard in the adult, and the variations produced by external conditions are less consid- erable. These facts have been fully confirmed by the re- searches of Despretz,3 Roger,8 and others. The experiments of W. P. Edwards have an important bearing upon our ideas of nutrition during the first periods of extra-uterine life. He found that in certain animals, par- ticularly dogs and cats, that are born with the eyes closed and in which the foramen ovale remains open for a few days, the temperature rapidly diminished when they were removed from the body of the mother, and that they then become reduced to a condition approximating that of cold-blooded animals ; but after about fifteen days, this change in tem- perature could not be effected. In dogs just born, the temperature fell after three or four hours' separation from the mother to a point but a few degrees above that of the surrounding atmosphere.* The views advanced by Edwards are fully illustrated in instances of premature birth, when the animal heat is much more variable than in infants at 1 W. F. EDWARDS, De V influence des agens physiques sur la vie, Paris, 1824, p. 234. 8 DESPRETZ, Recherches experimentales sur les causes de la chaleur animate. — Annales de chimie et de physique, Paris, 1824, tome xxvi., p. 338. Despretz found the temperature in three infants, between one and two days old, only 95-1°. 3 ROGER, De la temperature chez les enfants d Vetat phyxiologique et patho- logique. — Archives generates de medecine, Paris, 1845, 4me serie, tome ix., p. 264. 4 Op. tit., p. 132, et seq. 4:06 term,1 and in cases of persistence of the foramen ovale. In certain instances in which life has been prolonged under this abnormal condition, the individual is nearly in the condition of a cold-blooded animal. We can also understand the re- markable power of resistance to asphyxia in newly-born animals observed by Buffon, Legallois, and Edwards ; a for it is well known that cold-blooded animals will bear de- privation of oxygen much better than the higher classes. In adult life there does not appear to be any marked and constant variation in the normal temperature; but in old age, according to the observations of Davy, while the ac- tual temperature of the body is not notably reduced, the power of resisting refrigerating influences is diminished very considerably.3 There are no positive observations showing any constant differences in the temperature of the body in the sexes ; and it may be assumed that in the female, the animal heat is modified by the same influences and in the same way as in the male. Diurnal Variations in the Temperature of the Body. — Although the limits of variation in the animal temperature are not very extended, certain fluctuations are observed, de- pending upon repose or activity, digestion, sleep, etc., which it is necessary to take into account. These conditions, which are of a perfectly normal character, may produce changes in the temperature amounting to from one to three degrees. It has been ascertained that there are two well-marked periods iii the day when the heat is at its maximum. These, according to the most recent observations in Germany, are at eleven A. M. and four p. M. ; and it is a curious fact, that while all 1 W. F. Edwards noted a temperature in the axilla, of a little loss than 90°, two or three hours after birth, in an infant born at the seventh month ( Op. tit., p. 236). 2 See vol. i., Respiration, p. 420, et seq. 3 DAVY, On the Temperature of Man in advanced Age. — Physiological Re- searches, London, 1863, p. 4, et seq. ASTRAL HEAT. 407 observations agree upon this point, the .very elaborate ex- periments of Lichtenfels and Frohlich show that these periods are well-marked, even when no food is taken.1 Barensprung and Ladame further show that the fall in tem- perature during the night takes place sleeping or waking ; and that when sleep is taken during the day it does not disturb the period of the maximum, which occurs at about four p. M.* According to these experiments, at eleven in the morn- ing, the animal heat is at one of its periods of maximum ; it gradually diminishes for two or three hours and is raised again to the maximum at about four in the afternoon, when it again undergoes diminution until the next morning. The variations amount to from about 1° to 2*16.° The minimum is always during the night. The relations of the animal temperature to digestion are still somewhat indefinite. It is well known that activity of the digestive organs increases the consumption of oxygen, and, to a corresponding degree, the exhalation of carbonic acid ; but we have to assume that the production of heat is in direct ratio to the respiratory action in order to establish any relation between calorification and the digestion of ordinary food. It is easy to calculate that a given amount of oxygen will produce a definite quantity of carbonic acid, and will, by its union with carbon and hydrogen, generate a certain number of " units of caloric ; " but the mechanism of the production of animal heat is too complex and not well enough understood to admit of such positive reasoning. There is, indeed, no experimental evidence of any marked and constant change in the general temperature of the body during the ordinary process of digestion ; but it is none the less true that the quantity and quality of food bear 1 LICHTEXFELS UNO FROHLICH, Beobacldungen uber die Gesetze des Ganges der Pulzfrequenz und Korperwdrme in den normalen Zustanden. — Denkschriften der kaiserlichen Akad. der Wissenschaften, maihematiscli-naturwissenschaftliche Classe, Wien, 1852, Bd. iii., Zweite Abth., S. 113, et seq. 2 LOXGET, Traite de physiologic, Paris, 1869, tome ii., pp. 499, 534. 408 NUTRITION. a certain relation to calorification. This is inevitable from the connection of animal heat with the general process of nutrition ; but this relation is expressed in the con- nection of calorification with nutrition of the tissues, and not in the process of preparation or absorption of food. We shall see that when nutrition is modified by alimentation, the general temperature is always more or less affected ; and when the requirements of the system, as far as the genera- tion of heat is concerned, are changed, by climate or other- wise, alimentation is modified. One of the objects of ali- mentation and nutrition is to maintain the body at a nearly constant temperature. The influence of defective nutrition or inanition upon the heat of the body is very marked. John Hunter, in his experiments upon animal heat, made a few observations upon this point, and noted a decided fall in temperature in a mouse kept fasting.1 The same phenomena were also ob- served by Collard de Martigny ; a but Chossat, to whose memoir we have so fully referred in another volume under the head of inanition, noted the effects of deprivation of food upon the power of maintaining the animal temperature, in the most exact and satisfactory manner. This point has already been so fully considered that it is only necessary in this connection to note the general results. In pigeons, the extreme diurnal variation in temperature, under normal con- ditions, was found by Chossat to be 1'3.° During the prog- ress of inanition, the daily variation was increased to 5 '9,° with a slight, but well-marked diminution in the absolute temperature ; and the periods of minimum temperature were unusually prolonged. Immediately preceding death from starvation, the diminution in temperature became very rapid, the rate, in the observations on turtle-doves, being 1 Op. tit., p. 114. * COLLARD DE MARTIGNY, RecJierches experimentales sur les effete de I ^abstinence complete d'alimens solides et liquides. — Journal de physiologic, Paris, 1828, tomo viii., p. 163. ANIMAL HEAT. 409 from 7° to 11° per hour. Death usually occured when the diminution had amounted to about 30°. x When the surrounding conditions call for the develop- ment of an unusual amount of heat, the diet is always modified, both as regards the quantity and kind of food ; but when food is taken in sufficient quantity and is of a kind capable of maintaining proper nutrition, its composition does not affect the general temperature. If we were to adopt without reserve the view that the non-nitrogenized alimentary principles are the sole agents in the production of heat, we should certainly be able to determine either an increase in the animal heat or a greater loss of heat from the surface, in persons partaking largely of this kind of food. This, however, has not been shown to be true ; and the temperature of the body seems to be uniform in the same climate, even in persons living upon entirely different kinds of food. The elaborate observations of Dr. Davy are very conclusive on this point: "The similarity of tem- perature in different races of men is the more remarkable, since between several of them whose temperatures agreed, there was nothing in common but the air they breathed — some feeding on animal food almost entirely, as the Yaida — others chiefly on vegetable diet, as the priests of Boodho — and others, as Europeans and Africans, on neither exclu- sively, but on a mixture of both." a Xevertheless, the conditions of external temperature have a remarkable influence upon the diet. It is well known, for example, that in the heat of summer, the amount of meats and fat taken is small, and the succulent, fresh vegetables and fruits, large, as compared with the diet in the winter. But although the proportion of starchy mat- ters in many of the fresh vegetables used during a short season of the year is not large, these articles are equally deficient 1 CHOSSAT, Recherches experimentales sur ^inanition, Paris, 1843, p. 123. 2 DATY, Researches, Physiological and Anatomical, London, 1839, vol. i., p. 197. 410 NUTRITION. in nitrogenized matter. During the winter, the ordinary diet, composed of meat, fat, bread, potatoes, etc., contains a large amount of nitrogenized substance, as well as a con- siderable proportion of the hydro-carbons; and in the summer, we instinctively reduce the proportion of both of these varieties of principles, the more succulent articles taking their place. This is even more strikingly illus- trated by a comparison of the diet in the torrid or tem- perate and the frigid zone. Under the head of alimentation, we have already rioted the prodigious quantities of food con- sumed in the Arctic regions, and the effect of the continued cold upon the habits of diet of persons accustomed to a tem- perate climate. It is stated, on undoubted authority, that the daily ration of the Esquimaux is from twelve to fifteen pounds of meat, about one-third of which is fat. Dr. Hayes, the Arctic explorer, noted that with a temperature ranging from — 60° to — 70,° there was a continual craving for a strong, animal diet, particularly fatty substances. Some of the members of the party were in the habit of drinking the contents of the oil-kettle with evident relish.1 Under such conditions as those which surround inhabit- ants of temperate regions, in passing into the frigid zones a change in diet is imperatively demanded, in order to keep the animal temperature at the proper standard ; but when the climate is changed from the temperate to the torrid, the habits of life frequently remain the same. It is a pretty general opinion among physicians who have studied the sub- ject specially, that many of the peculiar disorders that affect those who have changed their residence from a temperate to a very warm climate are due, in a great measure, to the fact that the diet and habits of life are unchanged. The influence of alcoholic beverages upon the animal temperature has been studied chiefly with reference to the 1 HAYES, An Arctic Boat-Journey, Boston, 1860, pp. 257, 259, and American Journal of the Medical Sciences, Philadelphia, 1859, New Series, vol. xxxviii., p. 114, et seq. ANIMAL HEAT. 411 question of their use in enabling the system to resist exces- sive cold. Davy states that " the effect of wine, unless used in great moderation, is commonly lowering, that is, as to temperature, while it accelerates the heart's action, followed after a while by an increase of temperature." 1 We have already discussed somewhat fully the physiological effects of alcohol, and have shown that its use does not enable men to endure a very low temperature for a great length of time. This is the universal testimony of scientific Arctic explorers ; and Dr. Hayes particularly states, that " in almost any shape, it is not only completely useless, but positively injurious."2 The relations of animal heat to respiration and nutrition constitute a most interesting and important division of the subject, which will be more fully considered in discussing the various theories of calorification. As a rule, when the respira- tory activity is physiologically increased, as it is by exercise, bodily or mental, ingestion of food, or diminished external" temperature, the generation of heat in the body is correspond- ingly augmented ; and, on the other hand, it is diminished by conditions which physiologically decrease the absorption of oxygen and the exhalation of carbonic acid. The only positive experiments upon the influence of simple increase in the number and extent of the respiratory acts are those of Prof. Lombard. He found that when the respirations were increased in depth and frequency for ten minutes, there was a diminution of two degrees in the temperature over the radial artery. There was also a very slight lowering of the temperature, from '001 to *01 of a degree cent., in from a minute to a minute and a half after suspension of respiration. Prof. Lombard explains these phenomena by the mechani- cal effects of the condition of the lungs upon the arterial pressure.3 1 DAVY, Physiological Researches, London, 1863, p. 57. 2 HAYES, Observations on the Relations existing between Food and the Capabilities of Men to resist Low Temperatures. — American Journal of the Medical Sciences, Philadelphia, 1859, Xew Series, vol. xxxviii., p. 117. 3 LOMBARD, Recherches experimentales sur quetguts influences non etudiees 412 NUTRITION. The relations of animal heat to the general process of nutrition are most intimate. Any condition that increases the activity of nutrition and of disassimilation, or even any thing that increases disassimilation alone, will increase the production of heat. The reverse of this proposition is equally true. In pathology, the heat of the body may be increased by a deficient action of the skin in keeping down the tem- perature, without any increase in the activity of calorification. Influence of 'Exercise, etc., upon the Heat of the Body. — The influence of muscular activity upon animal heat is pecu- liarly interesting in connection with the theories of calorifi- cation, from the fact that the muscular system constitutes the greatest part of the organism ; and, as has repeatedly been shown by experiment, a muscle taken from a living animal is not only capable of contraction upon the application of a stimulus, but will perform for a time certain of the acts of nutrition and disassimilation, such as the appropriation of oxygen and the generation and exhalation of carbonic acid. The most complete repose of the muscular system is ob- served during sleep, when hardly any of the muscles are brought into action, except those concerned in tranquil respi- ration. There is always a notable diminution in the general temperature at this time. John Hunter found a difference, in man, of about one degree and a half.1 This fact has been confirmed by all who have studied the question experimen- tally. In the diurnal variations in the temperature of the body, the minimum is always during the night ; and, as we have already seen, this is not entirely dependent upon sleep, for a depression in temperature is constantly observed at that time, even when sleep is avoided.8 It is a matter of common observation, that one of the jusqu'ici de la respiration sur la temperature du corps humain. — Archives de physiologic, Paris, 1868, tome i., p. 496. 1 HUNTER, Observations on certain Parts of the Animal (Economy, London, 1792, p. 114. 2 See p. 407. ANIMAL HEAT. most effective methods of resisting the depressing influence of cold is to constantly exercise the muscles ; and it is well known, that after long exposure to intense cold, the tendency to sleep, which becomes almost irresistible, if indulged in, is followed by a very rapid loss of heat and almost certain death. It is not necessary to cite the accounts of travellers and others in support of these facts. In some animals, the amount of increase in the temperature during muscular activity is very great, and this is notably marked in the class of insects. In the experiments of Newport, on bees and other insects, a difference of about 27° was noted be- tween the conditions of complete repose and great muscular activity.1 The same facts were observed by Dutrochet, but he operated upon single insects, and observed an elevation of only a fraction of a degree.2 These facts are interesting, as showing the very great elevation of temperature that can be produced in the lower order of beings during violent ex- citement ; but in man, the differences, though distinct, are never very considerable, for the reason that violent mus- cular exertion is generally attended with greatly-increased action of the skin, which keeps the heat of the body within very restricted limits. In the experiments of Newport, the loss of heat from the surface was arrested by confining the insects in small glass bottles. The effects of active exercise, as in fast walking or riding, were very well observed by Dr. Davy. He found a con- stant elevation in the general temperature (taken under the tongue), amounting to between one and two degrees ; 3 but the most marked effects were observed in the extremities, especially when they were cold before taking the exercise.4 1 XEWPORT, On the Temperature of Insects, and its Connexion with the Func- tions of Respiration and Circulation in this Class of Invertebrate Animals — Philosophical Transactions, London, 1837, p. 281. 8 DUTROCHET, Recherches sur la chaleur propre des etres vivans d basse tempera- ture— Annales des sciences naturelles, Zoologie, Paris, 1840, 2me serie, tome xiii., p. 43, et seq. 3 DATY, Physiological Researches, London, 1863, p. 16. 4 Ibid., p. 11. 414 NUTRITION. The elevation in temperature that attends muscular action is produced directly in the substance of the muscle. This important fact was settled by the very interesting and ingenious experiments of Becquerel and Breschet. Intro- ducing a thermo-electric needle into the biceps of a man who used the arm in sawing wood for five minutes, these physiologists noted an elevation of temperature of one de- gree centigrade J (nearly two degrees Fahr.). The produc- tion of heat in the muscular tissue was even more strikingly illustrated by Matteucci, in experiments with portions of muscle from the frog. Not only did he observe absorption of oxygen and exhalation of carbonic acid and water after the muscle had been removed from the body of the animal, but he noted an elevation in temperature of about one de- gree Fahr., following contractions artificially excited.3 It is useless to multiply citations of experiments illus- trating the facts above noted, or to discuss elaborately the theoretical transformation of a given quantity of caloric into a definite and invariable amount of work. The conditions in the animal economy are such that we cannot exactly ap- preciate the loss of heat by the cutaneous and respiratory surfaces ; nor can we follow the processes in the body which involve the disappearance of oxygen and the evolution of carbonic acid ; the exact changes undergone by the hydro- carbonaceous elements of food and constituents of the body ; the amount of heat involved in the changes of the nitro- genized elements ; and, in short, we cannot make the correc- tions that are absolutely necessary before we can hope to re- duce the question of the oxidation of certain principles in the body, the development of heat, and the generation of mechan- ical force, to exact mathematical calculation. This has been attempted by Beclard 3 and others, who have endeavored to 1 BECQUEREL ET BRESCHET, Premier memoire sur la chaleur animale. — Annales de chimie et de physique, Paris, 1835, tome lix., p. 113. 2 MATTEUCCI, Recherches sur les phenomenes physiques et chimiques de la con- traction musculaire. — Comptes rendus, Paris, 1856, tome xlii., p. 651. 3 BECLARD, DC la contraction musculaire dans ses rapports avec la temperature ANIMAL HEAT. 4:15 establish the numerical value of" certain acts in what are called "mechanical equivalents of heat," or "heat-units." The observations of Beclard possess considerable physiolo- gical interest, but they are useful chiefly, if not entirely, in their positive results. Observations upon the influence of mental exertion on the temperature of the body have not been so numerous, but they are, apparently, no less exact in their results. Dr. Davy was the first to make any extended experiments on this point, and has noted a slight but constant elevation during " excited and sustained attention." x More lately, the same line of observation has been followed by Prof. Lombard, who employed much more exact methods of investigation. Prof. Lombard noted an elevation of temperature in the head during mental exertion of various kinds, but it was slight, the highest rise not exceeding the twentieth of a degree.8 It is stated, also, that the temperature of the body is in- creased by the emotions of hope, joy, anger, and all exciting passions; while it is diminished by fear, fright, and mental distress. Burdach, from whom the foregoing statement is taken, cites an example of an elevation of temperature from 96° to 99*5° in a violent access of anger, and a descent to 92*75° under the influence of fear, but the temperature soon returned to 9T'25°.3 The nervous system exerts a most important influence over the animal temperature, as it modifies the circulation and the nutritive processes in particular parts. The most interesting of these influences are transmitted through the sympathetic system. These will be discussed, to a certain extent, in connection with the theories of calorification ; but they cannot be taken up fully until we come to consider the animale. — Archives generates de medecine, Paris, 1861, 5me serie, tome xvii. The conclusions in this interesting memoir are to be found on page 277, et seq, 1 DATY, Physiological Researches, London, 1863, pp. 19, 51. 2 LOMBARD, Experiments on the Relations of Heat to Mental Work. — New York Medical Journal, 1867, vol. v., p. 198, et seq. 3 BURDACH, Traite de physiologic, Paris, 1841, tome is., p. 645. 416 inTTRITION. functions of the sympathetic system and its relations to nu- trition. In this connection, we will simply allude to certain phenomena manifested through the nervous system, without attempting to fully explain their mechanism. It is well known that when the sympathetic nerves going to a particular part are divided, the arterial coats are para- lyzed and dilated, the supply of blood is increased, nutrition is locally exaggerated and more or less modified, and the temperature of that particular part is increased by from five to ten degrees. An illustration of these facts in the ear of the rabbit, after division of the sympathetic in the neck, is a very common observation, which we have often verified in public demonstrations. All of these unnatural phenomena disappear on galvanizing the divided extremity of the nerve. These local modifications in the temperature have been fre- quently observed pathologically in the human subject. A number of curious local variations of temperature can be explained by direct or reflex action through the sympa- thetic nerves. Brown-Sequard and Lombard observed that pinching of the skin was soon followed by an elevation in temperature, and was attended also with a diminution in the temperature in the corresponding member on the opposite side. Sometimes the irritation of the upper extremities pro- duced changes in temperature in the lower limbs.1 Exam- ples of reflex action through the sympathetic nerves are given by Tholozan and Brown-Sequard, in a very interest- ing series of experiments. These physiologists found that lowering the temperature of one hand produced a considera- ble diminution in the temperature of the other hand, without any great depression in the general heat of the body ; and Brown-Sequard showed that by immersing one foot in water at 41°, the temperature of the other foot was diminished about 7° in the course of eight minutes.2 1 BROWN-SEQUARD ET LOMBARD, Experiences sur F influence de V irritation des nerfs de la peau sur la temperature des membres. — Archives de physiologic, Paris, 1868, tome i., p. 691. 8 THOLOZAN ET BROWN-SEQUARD, Recherche* experimentales sur quelqu'uns des AXIMAL HEAT. 4:17 ' The influence of the cerebro-spinal system upon the animal temperature is illustrated in cases of paralysis, when there is generally a very considerable diminution in the heat of the affected part. This fact was noted, many years ago, by Earle, who also observed that the temperature was in part restored under the influence of electricity. In one case of paralysis, he found the temperature of the hand of the af- fected side 70°, while the hand of the sound side was 92°. After the use of electricity for ten minutes, the temperature of the paralyzed hand was raised to 74°. Ten days after, the temperature of the hand on the paralyzed side was 71° before, and 77° after electricity had been employed.1 It is evident that if animal heat be one of the necessary attendant phenomena of nutrition, it must be greatly influ- enced by the state of the circulation. It has been a ques- tion, indeed, whether the modifications in temperature pro- duced by operating upon the sympathetic system of nerves be not due entirely to changes in the supply of blood. It is certain that whatever determines an increased supply of blood to any part raises the temperature ; and whenever the quantity of blood in any organ or part is considerably dimin- ished, the temperature is reduced. This fact is constantly illustrated in operations for the delegation of large arteries. It is well known that after tying a large vessel, the utmost care is necessary to keep up the temperature of the part to which its branches are distributed, until the anastomosing vessels become enlarged sufficiently to supply blood enough for healthy nutrition. In the experiments of Becquerel and Breschet, simple compression of the artery supplying the arm was sufficient to produce an immediate fall in the tem- perature.3 effete du froid sur Vliomme. — Journal de la physiologic, Paris, 1858, tome i., pp. 502, 505. 1 EARLE, Cases and Observations, illustrating the Influence of the Nervous Sys- tem in regulating Animal Heat. — Medico- Chirurgical Transactions, London, 1816, vol. vii., p. 176. 2 Loc. tit. 27 CHAPTER XIY. SOURCES OF ANIMAL HEAT. Connection of the production of heat with nutrition — Seat of the production of animal heat — Relations of animal heat to the different processes of nutri- tion— Relations of animal heat to respiration — The consumption of oxygen and the production of carbonic acid in connection with the evolution of heat — Exaggeration of the animal temperature in particular parts after division of the sympathetic nerve and in inflammation — Intimate nature of the calorific processes — Equalization of the animal temperature. THE most interesting question connected with calorifica- tion relates to the sources of heat in the living organism ; and a careful estimate of the physiological value of all the facts that have been positively established with reference to this point places the following proposition beyond any reasonable doubt : The generation of heat in the living animal organism is connected, more or less intimately, with all of the processes of nutrition and disassimilation, including, of course, the consumption of oxygen and the production of carbonic acid ; and this function is modified, to a greater or less degree, by all conditions that influence the general process of nutrition or the operation of the nutritive forces in particular parts. This proposition is not contradicted by any well-settled physiological facts or principles. Every one of the functions of the body bears more or less closely upon nutrition ; and all of the physiological modifications of the various func- tions, without exception, affect the process of calorification. AVe must bear in mind the fact, that in man and the warm- SOURCES CF AXMAL HEAT. 4:19 blooded animals generally, the maintenance of the tem- perature of the organism at a nearly fixed standard is a necessity of life and of the physiological action of the dif- ferent parts ; and that while heat is generated in the organism with an activity that is constantly varying, it is as constantly counterbalanced by physiological loss of heat from the cutaneous and respiratory surfaces. Variations in the activity of calorification are not to be measured by cor- responding changes in the temperature of the body, but are to be estimated by calculating the amount of heat lost. The ability of the human race to live in all climates is explained by the adaptability of man to different conditions of diet and exercise, and to the power of regulating loss of heat from the surface by appropriate clothing. Our proposition regarding the production of animal heat is in no wise opposed to the so-called combustion-theory, as it is received by most physiologists of the present day ; but it must be admitted that it is an unfortunate use of terms to apply the name combustion to the general process of nutri- tion, as is done by those who attempt to preserve, not only the ideas of the great author of this theory, but certain modes of expression, which were in accordance only with his limited knowledge of the phenomena of nutrition. If we speak of animal heat as the result of combustion of certain elements, it will be necessary constantly to refer to the difference between combustion as it occurs in the organism, and mere oxidation out of the body ; or to start with a full definition of what is to be understood by the term physiological combustion, which reduces itself simply to a definition of nutrition. Regarding calorification, then, as connected with all of the varied processes of nutrition, it remains for us to deter- mine the following questions : 1. In what part or parts of the organism is heat gen- erated ? 2. What is the relative importance in calorification, as 420 NUTKITION. regards the amount of heat generated, of the processes of nutrition, as we can study them separately ? 3. What are the principles invariably and of necessity consumed and produced in the organism in calorification ; and what is the relative importance of the principles thus consumed and the products thus generated and thrown off? 4. How far have we been able to follow those material transformations in the organism, which involve the consump- tion of certain principles, the production of new compounds, and the generation of heat ? Seat of the Production of Animal Heat. — Few if any physiologists at the present day hold to the opinion that there is any part or organ in the body specially and exclu- sively concerned in the production of heat. In the early his- tory of the oxidation-theory of Lavoisier, it was thought by some that the inspired oxygen combined with the hydro- carbons of the blood in the lungs, and that the heat of the body was generated almost exclusively in these organs ; but this idea has long since been abandoned. We have already f ally considered the question of loss or gain in the temperature of the blood in its passage through the lungs, and have seen that there is, to say the least, no constant elevation showing a generation of heat in these organs, suffi- cient to warm the blood, and through it the different parts of the body. If we find that the blood in coming from the lungs has about the same temperature as when it en- tered, it must be admitted that there is a certain generation of heat to compensate the loss by evaporation from the pul- monary surface. As far as we know, the heat that results from the mere physical solution of oxygen in the blood is all that is produced in the lungs. It is, indeed, estimated by Mar- chand, that the fixation of oxygen in this way is marked by an elevation of nearly 2° Fahr.1 There is no sufficient evi- 1 MARCHAND, Ueber die Einwirkung des Sauerstoffs auf das Blut und seine Bcstandtheile. — Journal fur praktische CJiemie, Leipzig, 1845, Bd. xxxv., S. 400. SOURCES OF ASTMAL HEAT. 421 deuce to show that the lungs are special organs of calorifi- cation ; and any generation of heat that takes place here is due, probably, to purely physical phenomena in the blood. The theory that all the respiratory changes, involving the consumption of oxygen, the production of carbonic acid, and the evolution of heat, take place in the blood as it cir- culates, was advanced many years ago by Lagrange and Hassenfratz ; 1 but recent investigations, showing the ap- propriation of oxygen and the evolution of carbonic acid by the tissues deprived of blood, and the evident production of heat in the muscular substance and in other parts, have completely overthrown this hypothesis. It is only necessary to refer back to the pages treating of the variations in the temperature of the blood in different parts, to show that heat is produced in the general system, and not in any particular organ, or in the blood as it circu- lates. The experiments of Matteucci, showing an elevation of temperature in a muscle excited to contraction after it had been removed from the body, and the observations of Becquerel and Breschet, showing increased development of heat by muscular contraction, are sufficient evidence of the production of heat in the muscular system ; 2 and, inasmuch as this constitutes by far the greatest part of the weight of the body, it is a most important source of animal heat. It has been demonstrated, by the experiments of Bernard, that the blood becomes notably warmer in passing through the abdominal viscera. This is particularly marked in the liver, and it shows that the large and highly-organized vis- cera are also important sources of caloric.3 As far as it is possible to determine by experimental demonstration, not only is there no particular part or organ 1 HASSENFRATZ, Memoire sur la combination de Foxygene avec le carlone et Vhy- drogene du sang, mr la dissolution de I'oxygene dans le sang, et sur la maniere dont le calorique se dfyage. — Annales de chimie, Paris, 1791, tome ix., p. 261. 2 See page 414. 3 See page 399. 422 NUTRITION. in the body endowed with the special function of calorifica- tion, but every part in which the nutritive forces are in operation produces a certain amount of heat; and this is probably true of the blood-corpuscles and other anatomical elements of this class. The production of heat in the body is general, and is one of the necessary consequences of the process of nutrition; but, with nutrition, it is subject to local variations, as is strikingly illustrated in the effects of operations upon the sympathetic system of nerves, and the phenomena of inflammation. Relations of Animal Heat to the different Processes of Nutrition. — Nutrition involves the appropriation of matters taken into the body, and the production and elimination of effete substances. In its widest signification, this includes the consumption of oxygen and the elimination of carbonic acid ; and, consequently, we may strictly regard respiration as a nutritive act. All of the nutritive processes go on to- gether, and they all involve, in most warm-blooded animals at least, a nearly uniform temperature. During the first periods of embryonic life, the heat derived from the mother is undoubtedly necessary to the development of tissue by a change of substance, analogous to nutrition, and even supe- rior to it in activity. During adult life, animal heat and the nutritive force are coexistent. It now becomes a question to determine whether there be any class of nutritive prin- ciples specially concerned in calorification, or any of the nu- tritive acts, that we have been able to study by themselves, which are exclusively or specially directed to the mainte- nance of the temperature of the body. These questions simply involve a review of considerations with regard to the relations of various of the functions to the production of heat. The supply of the waste of tissue being effected by meta- morphosis of alimentary matter — a process, the exact nature of which we have not been able to determine — it has thus RELATIONS OF ANIMAL HEAT TO NUTRITION. far been possible, only, to divide the food into different classes. Of these — leaving out oxygen — we will consider, in this connection, the organic matters, divided into nitro- genized and non-nitrogenized. The inorganic salts are al- ways combined with nitrogenized matter, and seem to pass through the organism without undergoing any considerable change ; and there is no evidence that they have any connec- tion, of themselves, with the production of heat. What is the relation to calorification of those processes of nutrition which involve the consumption of nitrogenized matter and the production of the nitrogenized excrementi- tious principles ? We cannot study these phenomena alone, isolated from the other acts of nutrition. We may confine an animal to a purely nitrogenized diet, and the heat of the body will be maintained at the proper standard ; but at all times there is a certain quantity of non-nitrogenized matter (sugar and perhaps fat) produced in the system, which is only formed to be consumed. We may starve an animal, and the tempera- ture will not fall to any very great extent until a short time before death. Here we may suppose that the process of de- position of nutritive matter in the tissues from the blood is inconsiderable, as compared with the transformation of the substance of these tissues into effete matter ; and it is almost certain that non-nitrogenized matter is not produced in the organism in quantity sufficient to account, by its destruction in the lungs, for the carbonic acid exhaled. It seems beyond question that there must be heat evolved in the body by oxi- dation of nitrogenized matter. When the daily amount of food is largely increased for the purpose of generating the immense amount of heat required in excessively cold cli- mates, the nitrogenized matters are taken in greater quan- tity, as well as the fats, although their increase is not in the same proportion. When, however, we endeavor to assign to the nitrogenized matters a definite proportion of heat-pro- ducing power, we are arrested by a want of positive knowl- 424 NUTRITION. edge with regard to the metamorphoses which these prin- ciples undergo ; and it is equally impossible to fix the rela- tive calorific value of the deposition of new material in repair of the tissues, and the change of their substance into eifete matter in disassimilation. From these facts, and other considerations that have already been fully discussed under different heads, it is evi- dent that the physiological metamorphoses of nitrogenized matter bear a certain share in the production of animal heat ; although, in connection with inorganic matter, their chief function seems to be the repair of the tissues endowed with the so-called vital properties. What is the relation of the consumption of non-nitro- genized matter to the production of animal heat ? It has been impossible to treat of the relations of the non-nitrogenized elements to nutrition without considering more or less fully the part these principles bear in the pro- duction of heat ; and we must refer the reader to the pre- vious chapter for a discussion of certain of these points.1 In this connection, we will simply state the relations that this class of principles is known to bear to calorification, and the facts upon which our statements are based. It has been pretty clearly shown that both sugar and fat are actually produced in the organism, even when the diet is strictly nitrogenized in its character; but we will only consider the relations of the non-nitrogenized elements in- troduced into the body, assuming that the principles of this class appearing de novo in the organism are the result of transformation of nitrogenized substances. As far as the destination of the amylaceous, saccharine, and fatty elements of food are concerned, we only know that they are incapable, of themselves, of repairing muscular tis- sue, and that they cannot sustain life. They are never dis- charged from the body in health in the form under which they enter ; but are in part or completely destroyed in nutri- 1 See page 378, et seq. RELATIONS OF ANIMAL HEAT TO NUTRITION. 425 tion. They are. completely destroyed in persons who, from habitual muscular exercise, have very little adipose tissue. "When their quantity in the food is large, they are not of necessity entirely consumed, but may be deposited in the form of adipose tissue. This, however, may be made to dis- appear by violent exercise, or under an insufficient diet. There can be no doubt that the non-nitrogenized class of alimentary principles is craved by the system in long-con- tinued exposure to extreme cold. This is particularly marked with regard to the fats. In all cold climates, fat is a most im- important element of food ; and in excessively cold regions, while the nitrogenized elements are largely increased, there is a very much larger proportional increase in the quantity of fat. These facts are very significant. If the non-nitrogen- ized elements of food — which are not always indispensable, though often very necessary articles — do not form tissue, are not discharged from the body, and are consumed in some of the processes of nutrition, it would seem that their change must involve the production of carbonic acid, perhaps also of water, and the evolution of heat. It is so difficult to ascer- tain the exact quantities of carbonic acid, watery vapor, etc., thrown off by the lungs, skin, and other emunctories, and to estimate the exact amount of heat produced and lost, that it is not surprising that calculations of the calorific power of different articles of food should be frequently erroneous; particularly as we have no means of knowing the exact calo- rific value of the nitrogenized principles. Though we may assume that the non-nitrogenized ele- ments of food are particularly important in the production of animal heat, and that they are not concerned in the repair of tissue, it must be remembered that the animal tempera- ture may be kept at the proper standard upon an exclu- sively nitrogenized diet ; and we cannot, indeed, connect calorification exclusively with the consumption of any sin- gle class of principles, nor with any single one of the acts of nutrition. 426 NUTRITION. Relations of Calorification to Respiration. — Respiration is one of the nutritive processes that can be closely studied by itself, as it involves the appropriation by the system of a single principle (oxygen), and that simply in solution in the blood. There can be no doubt that, of all the nutritive acts, respiration is, far more than any other, intimately connected with calorification. As far as the general process is con- cerned, the production of heat is usually in direct ratio to the consumption of oxygen and the exhalation of carbonic acid. In the animal scale, wherever we have the largest amount of heat produced, we observe the greatest respiratory activity. In man, whatever increases the generation of heat increases as well the consumption of oxygen and the elimina- tion of carbonic acid. The production of heat in warm- blooded animals is constant, and cannot be interrupted, even for a few minutes. The same is true of respiration. The tissues may waste for wrant of nourishment, but the heat of the body must be kept near a certain standard, which is almost always much higher than the surrounding temperature ; and there is no other nutritive act so constant and so immediately necessary to existence as the appropriation of oxygen. It is not surprising, then, that early in the history of the physi- ology of nutrition, before we knew, even, the exact condition and proportion of the gases in the blood, it should have, been thought that animal heat was the result of slow combustion of the hydro-carbons. The physiological history of respiration and of animal heat dates from the same series of discoveries. In the latter part of the last century, the great chemist, Lavoisier, discovered the intimate nature of the respiratory process, and applied the theory of the consumption of oxygen and the evolution of carbonic acid to calorification. We have already followed out the progress of this discovery in connection with respira- tion ; 1 and like nearly all of the great advances in physiologi- cal science, the distinctly-enunciated idea was foreshadowed 1 See vol. i., Respiration, p. 409, et seq. RELATIONS OF ANIMAL HEAT TO RESPIRATION. 427 by earlier writers. The most remarkable of these was Mayow, who, in 1667, and afterward in 1674, published a work on the Spiritua Nitro-aereus, and on respiration, in which he attributed to the nitro-aereous gas (oxygen) the property of combining with the blood in the lungs, producing the red color, and generating heat.1 These ideas, as well as those advanced by Crawford, near the time of the publication of the first observations of Lavoisier, were crude and indefinite, and contributed but little to our positive knowledge of the mechanism of calorification.2 It will not be necessary to treat, from a purely historical point of view, of the discoveries made by Lavoisier, as this has already been done sufficiently under the head of respi- ration.3 He undoubtedly went as far in his explanations of the phenomena of animal heat as was possible in the condi- tion of the science at the time. his investigations were made; and although he inevitably fell into some errors in his calcu- lations and deductions, he must forever be regarded as the -author of the first reasonable theory of the generation of heat by animals. The Consumption of Oxygen and Production of Car- bonic Acid in Connection with the Evolution of Heat. — As far as it has been possible to determine by actual experiment, 1 MAYOW, Tradatiis quinque Jfedico-physici. Quorum primus agit de Salnitro, et Spiritu Nitro-aereo. Secundus de Respiratione, etc., Oxonii, 1674, p. 151, et seq. The first edition of the work on Respiration was published in 1767. 2 CRAWFORD, Experiments and Observations on Animal ffeat, London, 1788, second edition, p. 354, et seq. Crawford published the first edition of his work in 1779, but the second edition, in which his views are avowedly made to cor- respond with the observations of Lavoisier, is the only one at all accessible. From all we can learn of the matter contained in the first edition, from extracts and references in other treatises, Crawford's ideas were not in advance of those presented by Lavoisier to the Academy of Sciences, in 1777. 3 The various papers published by Lavoisier and Seguin, and Lavoisier and de la Place, are scattered through the volumes of memoirs of the French Academy of Sciences, from ITTTto 1790. An exhaustive analytical review of these memoirs is given by Gavarret (De la chaleur produite par les etres vivants, Paris, 1855, p. 165, et seq.). 428 NUTRITION. all animals, even those lowest in the scale, appropriate oxy- gen and eliminate carbonic acid ; and this is equally true of all living tissues. In 1775, Lavoisier noted the fact that the gas obtained by decomposing the oxide of mercury was more active than the air in maintaining the respiration of animals.1 Two years later, he compared oxidation by respiration in animals to ordinary combustion, and advanced the hypothe- sis that this action was the cause of the constant temperature of animals of about 32|-° Reaumur.2 A little later, he pub- lished the remarkable experiments in which he estimated the amount of " combustion " in a Guinea-pig, by collecting the carbonic acid exhaled, and compared it with the amount of heat lost by the same animal in a definite time.3 Here he met with some difficulty, and found that the heat pro- duced, according to his calculations, did not quite equal the heat lost. In later memoirs he ascertained positively that the carbonic acid exhaled in respiration did not represent the totality of the oxygen consumed ; and he attributed the production of heat in part to the union of oxygen with hy- drogen.4 Since it has been ascertained that oxygen is dis- solved, as oxygen, in the arterial blood, that it disappears in part or entirely in the capillary circulation, that carbonic acid is taken up by the venous blood, both in solution and in feeble combination in the bicarbonates, to be discharged in the lungs by displacement and the action of the pneumic 1 LAYOISIER, Memoire sur la nature du principe qui se combine avec les metaux pendant leur calcination, et qui en augmente lepoids. — Histoire de V academic royale des sciences, annee, 1775, Paris, 1778, pp. 521, 525. 2 LAVOISIER, Memoire sur la combustion en general. — Histoire de V academic royale des sciences, annee, 1777, Paris, 1780, p. 599. 3 LAVOISIER ET DE LA PLACE, Memoire de la ckaleur. — Histoire de Vacademie royale des sciences, annee, 1780, Paris, 1784, p. 407. 4 LAVOISIER, Memoire sur les alterations qui arrivent d Fair dans plusieurs circonstances ou se trouvent les Jiommes reun'ts en societe. — Histoire de la societe royale de medecine, annees, 1782 et 1783, Paris, 1787, p. 574. SEGUIN ET LAVOISIER, Premier memoire sur la respiration des animaux. — Histoire de Vacademie royale des sciences, annee, 1789, Paris, 1793, p. 566, et seq. RELATIONS OF ANIMAL HEAT TO RESPIRATION. 429 acid, and that the tissues themselves have the property of appropriating oxygen and exhaling carbonic acid, those who adopt the theory of Lavoisier have simply changed the seat of oxidation from the lungs to the general system. It has been proven beyond question that oxygen, of all the principles introduced from without, is the one most im- mediately necessary to nutrition; and it differs from the class of substances ordinarily known as alimentary, only in the fact that it is consumed more promptly and constantly. In the same way, carbonic acid is to be regarded as an ele- ment of excretion, like urea, creatine, etc., differing from them only in the immediate necessity for its elimination.1 As the comparatively slow excretion of urea and other nitro- genized matters is connected with the ingestion of ordinary alimentary substances that are slowly appropriated by the tissues, so the rapid elimination of carbonic acid is connected with the equally rapid appropriation of oxygen. There is no reason why we should not regard carbonic acid, like other effete substances, as an excretion, the result of disassimila- tion of the tissues generally ; but, more closely than any, it is connected with the rapid and constant evolution of heat. This view is proven by the experiments of Spallanzani,3 W. F. Edwards,3 and Collard de Hartigny.4 All of these eminent observers demonstrated, beyond a doubt, that car- bonic acid may be formed in the system and exhaled, in animals deprived of oxygen, and that its exhalation will take place from a piece of tissue freshly removed from a 1 Collard de Martigny, who was one of the most powerful opponents of the combustion-theory of animal heat, concludes the account of his experi- ments on the production of carbonic acid with the statement that it " is a prod- uct of assimilative decomposition, secreted hi the capillaries, and excreted by the lungs" (Journal de physiologic, Paris, 1830, tome x., p. 161). 8 SPALLAXZAXI, Jfemoires sur la respiration, Geneve, 1803, pp. 86, 343. 3 EDWARDS, De linfluen.ee, des agens physiques sur la vie, Paris, 1824, p. 443, et seq., and p. 455, et seq. * COLLARD DE MARTIGNY, Recherches experimentales et critiques sur fabsorption et sur F exhalation respiratoires. — Journal de physiologic, Paris, 1830, tome x., p. 124. 430 NUTRITION. living animal and placed in an atmosphere of hydrogen or nitrogen. Experiments on the influence of the sympathetic nerves upon the temperature of particular parts have completed the chain of evidence in favor of the localization of the heat- producing function in the tissues. It is not our purpose to discuss the relations of the sympathetic system to nutrition, deferring this subject until we come to treat specially of the nervous system ; but the facts bearing on calorification are briefly as follows : If the sympathetic nerve be divided in the neck of a rabbit, or any other warm-blooded animal, the side of the head supplied by this nerve will become from flve to eight or ten degrees warmer than the opposite side, or than the rest of the body. This observation we have repeatedly veri- fied. The conditions under which this local exaggeration of the animal heat is manifested are, dilatation of the arteries of supply of the part,- so that it receives very much more blood than before, and increased activity of the general process of nutrition. It also has been observed, in experiments upon the horse, that the blood coming from the part is red, and con- tains very much more oxygen than ordinary venous blood.1 The recent observations of MM. Estor and Saint-Pierre show that the blood coming from inflamed parts, in which there is a considerable elevation above the normal temper- ature, is red, and contains from fifty to two hundred and fifty per cent, more oxygen than ordinary venous blood.2 These facts are regarded as inconsistent with the view that the temperature of parts is due chiefly to oxidation; but when we consider the fact that, in the conditions above mentioned, the actual quantity of blood circulating in these 1 BERNARD, Sur la quantite d'oxygene que contient le sang veneux dcs organes glandulaires, d Petal def auction et d Tetat de repos. — Comptes rendus, Paris, 1858, tome xlvii., p. 398, note. 2 ESTOR ET SAINT-PIERRE, Recherches experimentales sur les causes de la colora- tion rouge des tissus enflammes. — Journal de Panatomie, Paris, 1864, tome i., p. 412, and Du siege dcs combustions respiratoires. — Ibid., 1865, tome ii., p. 314. RELATIONS OF ANIMAL HEAT TO RESPIRATION. 431 parts is increased many times, the error in the deduction is palpable enough. It is not sufficient to show that the blood coming from an inflamed tissue, with an abnormally high temperature, contains more oxygen than under ordinary conditions, but it is indispensable to demonstrate that the absolute quantity of oxygen consumed is diminished. For example, if the venous blood should contain double the normal* proportion of oxygen, but the quantity coming from the part should be increased threefold, it is evident that the actual consumption of oxygen would be doubled. As an illustra- tion, let us assume that, in one minute, 100 parts of blood, containing 10 parts of oxygen, circulate through a member, losing in its passage 7*5 parts of oxygen, thus leaving a pro- portion of 2*5 of oxygen for the venous blood ; if the part become inflamed, let us suppose that during the same period, 300 parts of blood, with 30 parts of oxygen, pass through, but that the venous blood contains five per cent, of oxygen, or 15 parts. That would show an actual consumption of 15 parts of oxygen in inflammation, against 7'5 under normal nutrition. Estor and Saint-Pierre do not state the amount of increase in the quantity of blood circulating through inflamed tissues, but they admit that, " in inflammation, the vessels are dilated, and the current of blood is more rapid." * An increase in the absolute quantity of blood passing through parts after divi- sion of the sympathetic nerves distributed to the coats of the blood-vessels has been observed by all who have experi- mented on the subject ; and the increase is probably greater than that which we have assumed in our argument. An additional argument in favor of our interpretation of the experiments of Estor and Saint-Pierre is the fact, noted by them, that the blood from inflamed parts contains more carbonic acid than ordinary venous blood.9 Taking into account all the facts bearing upon the ques- tion, there can be little doubt, that while the processes of 1 Journal de V anatomic, Paris, 1865, tome ii., p. 314. 1 Idem., Paris, 1864, tome i., p. 412. 432 NUTRITION. nutrition and disassimilation, involving changes in the nitro- genized constituents of the blood and the tissues, are not disconnected with calorification, the production of heat by animals is most closely related to the appropriation of oxygen and the formation of carbonic acid. Intimate Nature of the Calorific Processes. — A compre- hension of the intimate nature of the calorific processes involves simply an answer to the question, how far we can follow the material transformations in the organism, which involve the consumption of certain principles, the production of new compounds, and the evolution of heat. As regards the nature of the intermediate processes connecting the dis- appearance of oxygen with the production of carbonic acid, we can only explain it by reciting the simple facts. Oxygen disappears, carbonic acid is formed, and the carbon is fur- nished, perhaps by the tissues, perhaps by the blood, probably by both. It is probable that the intermediate changes are more simple and rapid than those which intervene between the appropriation of nitrogenized nutritive matter and the forma- tion of the nitrogenized excretions ; but we have never been able to follow either of these processes through all of their different phases. We must be content, in the present con- dition of our positive knowledge, to regard calorification as one of the attendant phenomena of nutrition ; and we have only to study as closely as possible the facts with regard to the disappearance of certain principles and the formation of effete matters, that are always and of necessity associated with the development of heat. Equalization of the Animal Temperature. — A study of the phenomena of calorification in the human subject has shown that under all conditions of climate the general heat of the body is equalized. Nearly always, the surrounding temperature is below the standard of the body, and there is, of necessity, an active production of caloric. Under all con- EQUALIZATION OF THE ANIMAL TEMPERATURE. 433 ditions, there is more or less loss of heat by evaporation from the general surface, and when the surrounding atmosphere is very cold, it becomes desirable to reduce this loss to the mini- mum. This is done by appropriate clothing, which must certainly be regarded as a physiological necessity. The proper kind of clothing, the conducting power of different materials, their porosity, etc., form important questions in practical hygiene, and their full discussion belongs to special treatises. Clothing protects from excessive heat as well as cold. Thin, porous articles moderate the heat of the sun, equalize evaporation, and afford great protection in hot climates. In excessive cold, clothing is of the greatest importance in preventing the escape of heat from the body. When the body is not exposed to currents of air, the gar- ments are chiefly useful as non-conductors, imprisoning many layers of air, warmed by contact with the person. It is fur- ther very important to protect the body from the wind, which increases so greatly the loss of heat by evaporation. It is wonderful, however, how intense a cold may be resisted by healthy men under proper conditions of alimentation and exercise and with the protection of appropriate clothing, as in Arctic explorations, when the thermometer has for days ranged from —60° to —70° Fahr.1 When from any cause there is a tendency to undue ele- vation of the heat of the body, cutaneous transpiration is increased, and the temperature is kept at the proper stand- ard. We have already considered this question in treating of the action of the skin, and have noted facts showing that men can work when exposed to a heat much higher than that of the body itself. The amount of vapor that is lost lender these conditions is sometimes enormous, amounting to from two to four pounds in an hour.2 We have often noted a loss of between two and three pounds after exposure for less 1 HAYES, An Arctic Boat-Journey, Boston, 1860, pp. 257, 259, and American Journal of the Medical Sciences, Philadelphia, 1859, Xew Series, vol. xxxviii., p. 114, et seq. 2 See page 140. 28 434 NUTRITION. than an hour to a steam-bath of from 110° to 116° ; and a much greater elevation of temperature, in dry air, can be tolerated with impunity. We have alluded to some of the ob- servations on the temperatures that could be borne without bad results, in connection with the question of variations in the heat of the body. In the experiments of Delaroche and Berger, the temperature was considerably under 200°. 1 Tillet recorded an instance of a young girl who remained in an oven for ten minutes without inconvenience, at a temperature of 130° Reaumur, or 324*5° Fahr.2 Dr. Blagden, in his noted experiments in a heated room, made in connection with Drs. Banks, Solander, Fordyce, and others, found in one series of observations, that a temperature of 211° could be easily borne ; and at another time, the heat was raised to 260°. 3 Chabert, who exhibited in this country and in Europe under the name of the " fire-king," is said to have entered ovens at from 400° to 6000.4 Under these extraor- dinary temperatures, the body is protected from the radiated heat by clothing, the air is perfectly dry, and the animal heat is kept down by excessive exhalation from the surface. It is a curious fact, that after exposure of the body to an intense dry heat or to a heated vapor, as in the Turkish and Russian baths, when the general temperature is somewhat raised and the surface is bathed in perspiration, a cold plunge, which checks the action of the skin almost imme- diately, is not injurious, and is rather agreeable. This pre- sents a striking contrast to the effects of sudden cold upon a system, heated and exhausted by long-continued exertion. In the latter instance, when the perspiration is suddenly checked, serious disorders of nutrition, inflammations, etc., 1 See page 397. 2 TILLET, Memoire sur les degres extraordinaires de chaleur auxquelles les hommes et les animaux sont capables de resister. — Histoire de Vacademie rot/ale des sconces, annee, 1764, Paris, 1767, p. 188. 3 BLAGDEN, Experiments and Observations in an heated Room. — Philosophical Transactions, London, 1775, pp. 196, 484. 4 DUNGLISON, Human Physiology, Philadelphia, 1856, vol. i., p. 598. EQUALIZATION OF THE ANIMAL TEMPERATUBE. 435 are very liable to occur. The explanation of this, as far as we can present any, seems to be the following : When the skin acts to keep down the temperature of the body in sim- ple exposure to external heat, there is no modification in nutrition, and the tendency to an elevation of the animal temperature comes from causes entirely external. It is a practical observation that no bad effects are produced, under these circumstances, by suddenly changing the external con- ditions; but when the animal temperature is raised by a modification of the internal nutritive processes, as in pro- longed muscular effort, these changes cannot be suddenly arrested ; and a suppression of the compensative action of the skin is apt to produce disturbances in nutrition, very often resulting in inflammations. CHAPTEK XV. MOVEMENTS GENERAL PROPERTIES OF CONTRACTILE TISSUES. Amorphous contractile substance — Ciliary movements — Movements due to elas- ticity— Varieties of elastic tissue — Muscular movements — Physiological anatomy of the involuntary muscles — Mode of contraction of the involun- tary muscular tissue — Physiological anatomy of the voluntary muscles — Primitive fasciculi — Sarcolemma — Fibrillse — Fibrous and adipose tissue in the voluntary muscles — Connective tissue — Blood-vessels and lymphatics of the muscular tissue — Connection of the muscles with the tendons — Chemical composition of the muscles — Physiological properties of the mus- cles— Elasticity — Muscular tonicity — Sensibility of the muscles — Muscular contractility, or irritability. THE organic, or vegetative functions of animals involve certain movements ; and almost all animals possess, in addi- tion, the power of locomotion. "Very many of these move- ments have, of necessity, been considered in connection with the different functions ; as the action of the heart and ves- sels in the circulation ; the uses of the muscles in respira- tion ; the ciliary movement in the air-passages ; the muscular acts in deglutition ; the peristaltic movements ; and the me- chanism of defecation and urination. There remain, how- ever, certain general facts with regard to various kinds of movement and the mode of action of the different varieties of muscular tissue, that will demand more or less extended consideration. As regards the exceedingly varied and com- plex acts concerned in locomotion, it is difficult to fix the limits between anatomy and physiology. A full compre- hension of such movements must be preceded by a complete AMORPHOUS CONTRACTILE SUBSTANCE. 437 descriptive anatomical account of the passive and active or- gans of locomotion ; and special treatises on anatomy almost invariably give the uses and actions, as well as the structure and relations of these parts. Amorphous Contractile Substance. — In some of the very lowest orders of beings, in which hardly any thing but amor- phous matter and a few granules can be recognized by the microscope, certain movements of elongation and retraction of their amorphous substance have been observed. In the higher animals, similar movements have been noticed in cer- tain of their structures, such as the leucocytes, the contents of the ovum, epithelial cells, and connective-tissue cells. These movements are generally simple changes in the form of the cell, nucleus, or whatever it may be. They are sup- posed to depend upon an organic principle called sarcode, or protoplasm ; 1 but it is not known that such movements are characteristic of any one definite proximate principle, nor is it easy to determine their cause and their physiological im- portance. In the anatomical elements of adult animals of the higher classes, the sarcodic movements usually appear slow and gradual, even when viewed with high magnifying powers; but in some of the very lowest orders of* being, where these movements serve as the means of progression, they are more rapid. It does not seem possible, in the present condition of our knowledge, to explain the nature and cause of the move- ments of homogeneous contractile substance ; and it must J5 J be excessively difficult, if not impossible, to observe directly the effects of different stimuli, in the manner in which we study the movements of muscles. As far as we can judge, 1 KUHXE, Untersuchungen uber das Protoplasma und die Contractilitat, Leipzig, 1864. In this very elaborate memoir almost all varieties of contraction are re- ferred to the action of the single principle, protoplasm. The chief physiological interest, however, is attached to this explanation of muscular contraction ; but there are few writers of authority who accept the view that it is entirely due to the presence of the so-called protoplasm. 438 MOVEMENTS. they are analogous to the ciliary movements, the cause of which is equally obscure. Ciliary Movements. — The epithelium covering certain of the mucous membranes is provided with little hair-like processes upon the free portion of the cells, called cilia. These are in constant motion, from the beginning to the end of life, and produce currents on the surfaces of the mem- branes to which they are attached, the direction being always from within outward. In many of the infusoria, the ciliary motion serves as a means of progression, effects the intro- duction of nutriment into the alimentary canal, and, indeed, is almost the sole agent in the performance of the func- tions involving movement. Even in higher classes, as the mollusca, the movements of the cilia are of great impor- tance. In man, and the warm-blooded animals generally, the ciliated or vibratile epithelium is of the variety called columnar, conoidal, or prismoidal. The cilia are attached to the thick ends of the cells, and form on the surface of the membrane a continuous sheet of vibrating processes. It is unnecessary to describe in detail the size and form of the cells provided with cilia, as their variations in different situations have been and will be considered in connection with the physiological anatomy of different parts. In general structure, the ciliary processes are entirely homogeneous, and gradually taper from their attachment to the cell to an ex- tremity of excessive tenuity. Although anatomists, from time to time, have described striae at the bases of the cilia, and have attempted to explain their motion by a kind of muscular action, no well-defined structure has ever been actually demonstrated in their substance. Certain currents were observed in the infusoria, mollusca, and other of the lower order of animals, long before the structure of the cilia had been accurately described ; but in 1835, Purkinje and Yalentin, in a very elaborate memoir, described these structures fully, and noted the situations CILIAHY MOVEMENTS. 439 in which they are to be found in the human subject.1 Their presence has been demonstrated on the following surfaces : The respiratory passages, including the nasal fos- sae, the pituitary membrane, the summit of the larynx, the bronchial tubes, the superior surface of the velum palati, and the Eustachian tubes ; the sinuses about the head ; the lachrymal sac and the internal surface of the eyelids ; the geni- tal passages of the female, from the middle of the neck of the uterus to the extremities of the Fallopian tubes ; and the ven- tricles of the brain. They probably exist also at the neck of the capsule of Miiller, in the cortical substance of the kid- ney. In these situations, to each cell of conoidal epithelium are attached from six to twelve prolongations,2 about ssooo of an inch in thickness' at their base, and from yoW *° ToVrr °f an inch in length.3 The appearance of the cilia in detached cells is repre- sented in Fig. 15. When seen in situ, they appear regularly disposed on the surface, are of nearly equal length, and are all slightly inclined in the -,. .. f» . T . «,, . , Ciliated epithelium. (LOKGET, direction Ot the Opening OI the Cavity Tralte de physiologic, Paris, •,.-,,,, 1869, tome ii., p. 579.) lined by the membrane. The ciliary motion is one of the most beautiful physio- logical demonstrations that can be made with the micro- scope. By scraping the roof of the mouth of a living frog, the mucous membranes of the respiratory passages in a warm-blooded animal just killed, the beard of the oyster or clam, and placing the preparation, moistened with a little serum, under a magnifying power of about two hundred and 1 PURKINJE AND VALENTIN*, Discovery of Continual Vibratory Motions, pro- duced by Cilia, as a general Phenomenon in Reptiles, Birds, and Mammiferous Animals. — Edinburgh New Philosophical Journal, 1835, vol. xix., p. 118, et seq. * BECLARD, Traite elementaire dt physiologic humaine, Paris, 1859, p. 497. 3 POUCHET, Precis d?histologie humaine, Paris, 1864, p. 189. 440 ' MOVEMENTS. fifty diameters, the currents produced in the liquid will be strikingly exhibited. The movements may be studied in de- tached cells, in the human subject, by introducing a feather into the nose, when a few cells will be removed with the mucus, and can be observed in the same way.1 This demon- stration serves to show the similarity between the movements in man and in the lower orders of animals. When the move- ments are seen in a large number of cells in situ, the ap- pearance is very graphically illustrated by the apt comparison of Henle to the undulations of a field of wheat agitated by the wind.2 In watching this movement, it is usually seen to gradually diminish in rapidity, until what at first ap- peared simply as a current, produced by movements too rapid to be studied in detail, becomes revealed as distinct undulations, in which the action of individual cilia can be readily studied. Purkinje and Valentin describe several kinds of movement,3 but the most common is a bending of the cilia, simultaneously or in regular succession, in one di- rection, followed by an undulating return to the perpendicu- lar. The other movements, such as the infundibuliform, in which the point describes a circle around the base, the pen- dulum-movement, etc., are not common, and are unimpor- tant. The combined action of the cilia upon the surface of a mucous membrane, moving as they do in one direction, is to produce currents of considerable power. This may be illus- trated under the microscope by covering the surface with a liquid holding little solid particles in suspension. In this case the granules are tossed from one portion of the field to another with considerable force. It is not difficult, indeed, to meas- ure in this way the rapidity of the ciliary currents. In the frog it has been estimated at from ^-g- to T^ of an inch per second, the number of vibratile movements being from 1 BECLARB, op. cit., p. 497. 2 HENLE, Traite tfanatomie generate^ Paris, 1843, tome i., p. 263. 3 Loc. cit. CILIAEY MOVEMENTS. 441 seventy-five to one hundred and fifty per minute. In the fresh water polyp the movements are more rapid, being from two hundred and fifty to three hundred per minute.1 There is no reliable estimate of the rapidity of the ciliary currents in man, but they are probably more active than in animals low in the scale.a The movements of cilia, like those observed in fully de- veloped spermatozoids, seem to be entirely independent of nervous influence, and are affected only by purely local con- ditions. They will continue, under favorable circumstances, for more than twenty-four hours after death, and can be seen in cells entirely detached from the body when they are moist- ened with proper fluids. Beclard states that in the tortoise, the movement may be preserved for several weeks after the death of the animal.3 When the cells are moistened with pure water, the activity of the movement is at first increased ; but it soon disappears as the cells become swollen. Acids arrest the movement, but it may be excited by feeble alka- line solutions. All abnormal conditions have a tendency either to retard or to abridge the duration of the ciliary mo- tion. It is true that when the movement is becoming feeble, it may be temporarily restored by very dilute alkaline solu- tions, but the ordinary stimuli, such as are capable of exciting muscular contraction, are without effect. Purkinje and Valentin, Sharpey, and others have attempted to excite the movements of cilia by galvanic stimulus, but without success.4 Anaesthetics and narcotics, which have such a decided effect upon muscular action, have no influence upon the cilia. It is useless to follow the speculations that have been 1 BECLARD, Traite elementaire de physiologic, Paris, 1859, p. 498. 8 A pupil of M. Bernard, M. Calliburces, has devised a very ingenious in- strument for measuring the rapidity of the ciliary motion (BERNARD, Lemons sur les proprietes &s tissus vivants, Paris, 1866, p. 139, et seg.). 3 Zoo. cit. 4 SHARPEY, Cyclopaedia of Anatomy and Physiology, London, 1835-'36, vol. i., p. 634, Article, Cilia. 442 MOVEMENTS. advanced to account for the movement of cilia. There is no muscular structure, no connection with the nervous system, and there seems to be no possibility of explaining the move- ment except by a bare statement of the fact that the cilia have the property of moving in a certain way so long as they are under normal conditions. As regards the physiological uses of these movements, it is sufficient to refer to the physi- ology of the parts in which cilia are found, where the pecu- liarities of their action are considered more in detail. In the lungs and the air-passages generally, and the genital passages of the female, the currents are of considerable im- portance ; but it is difficult to imagine the use of these move- ments in certain other situations, as the ventricles of the brain. Movements due to Elasticity. — There are certain impor- tant movements in the body that are due simply to the action of elastic ligaments or membranes. These are entirely distinct from muscular movements, and are not even to be classed with the movements produced by the resiliency of muscular tissue, in which that curious property, called muscular toni- city, is more or less involved. Movements of this kind are never excited by nervous, galvanic, or other stimulus, but consist simply in the return of movable parts to a certain position after they have been displaced by muscular action, and the reaction of tubes after forcible distention, as in the walls of the large arteries. Elastic Tissue. — Most writers of the present day adopt the division of the elastic tissue, first made by Henle,1 into three varieties. This division relates to the size of the fibres ; and all varieties are found to possess essentially the same chemical composition and general properties, includ- ing the elasticity for which they are so remarkable. On account of the yellow color of this tissue, presenting, as it does, a strong contrast to the white, glistening appearance 1 HENLE, Traite & anatomic generale, Paris, 1843, tome i., p. 430. MOVEMENTS DUE TO ELASTICITY. 443 of the inelastic fibres, it is frequently called the yellow elas- tic tissue. The first variety of elastic tissue is composed of small fibres, generally intermingled with fibres of the ordinaiy inelastic tissue. These are sometimes called by the French, dartoic fibres. They possess all the chemical and physical characters of the larger fibres, but are excessively minute, measuring from 25i00 to ^^ or -^^ of an inch in diame- ter.1 If we add acetic acid to a preparation of ordinary connective tissue, the inelastic fibres are rendered semitrans- parent, but the elastic fibres are unaffected and become very distinct. They are then seen isolated — that is, never arranged in bundles — always with a dark, double contour, branching, brittle, and when broken, their extremities curled and pre- senting a sharp fracture, like a piece of India-rubber. These fibres pursue a wavy course through the bundles of inelastic fibres in the areolar tissue and in most of the ordinary fibrous membranes, and here they exist as an accessory anatomical element. They are found in greater or less abundance in the situations just mentioned ; also in the ligaments (but not the tendons) ; in the layers of involuntary muscular tissue ; the true skin ; the true vocal cords ; the trachea, bronchial tubes, and largely in the parenchyma of the lungs ; the external layer of the large arteries ; and, in brief, in nearly all situa- tions in which the ordinary connective tissue exists. The second variety of elastic tissue is composed of fibres, larger than the first, ribbon-shaped, with well-defined out- lines, anastomosing, undulating or curved in the form of the letter S, presenting the same curled ends and sharp fracture as the smaller fibres. These measure from g^ to ^Vfr of an inch in diameter.2 Their type is found in the ligamenta subflava and the ligamentum nuchse. They are also found 1 POUCHET, Freds cCJustologie humaine, Paris, 1864, p. 62. In order to secure as much uniformity as possible in our measurements of microscopic structures, we have generally followed the French school of histologists. 2 POUCHET, loc. cit. 444 MOVEMENTS. in some of the ligaments of the larynx, the stylo-hyoid liga- ment, and the suspensory ligament of the penis. The form and arrangement of these fibres may be very beautifully demonstrated by tearing off a portion of the ligamentum nuchse and lacerating it with needles in a drop of acetic acid. The action of the acetic acid renders the accessory structures of the ligament transparent, and the elastic fibres become very distinct. The same may be accomplished by boiling the tissue for a short time in caustic soda. The third variety of elastic tissue can hardly be said to consist of fibres, their branches are so short and their anas- tomoses so frequent. This kind of structure is found form- ing the middle coat of the large arteries, and has already been described in connection with the vascular system.1 The fibres are very large, flat, with numerous short branches, " which unite again with the trunk from which they originate or with adjacent fibres. In certain situ- ations, the interstices are considerable, in proportion to the diameter of the fibres, and the anastomosing branches are given off at acute angles, so that they follow pretty closely the direction of the trunks, and the anastomoses do not dis- turb the longitudinal direction and parallelism of the fibres. Indeed, the anastomoses are so numerous, and the intervals so small, proportionally to the fibres, that we would believe we had under observation a reticulated membrane, present- ing openings, rounded and oval, some large and others small." 2 These anastomosing fibres, forming the so-called fenestrated membranes, are arranged in layers, and the struc- ture is sometimes called the lamellar elastic tissue. The great resistance which the elastic tissue presents to chemical action serves to distinguish it from nearly every other structure in the body. "We have already seen that it 1 See vol. i., Circulation, p. 244. 2 The above description, taken from Henle's general anatomy, conveys a very clear idea of the arrangement of the large elastic fibres in the " fenestrated membranes" (HENLE, Traite d'anaiomie generate, Paris, 1843, tome i., p. 431). MUSCULAR MOVEMENTS. 445 is not affected by acetic acid or by boiling with caustic soda. It is not softened by heat, by prolonged boiling in water, but is slowly dissolved, without decomposition, by sulphuric, nitric, and hydrochloric acid, the solution not being precipi- table by potash. Its organic base is a nitrogenized sub- stance called elasticine ; l containing carbon, hydrogen, oxy- gen, and nitrogen, without sulphur. This is supposed to be identical with the sarcolemma of the muscular tissue.8 The purely physical property of elasticity plays an im- portant part in many of the animal functions. TVe have already had an example of this in the action of the large arteries in the circulation, and in the resiliency of the paren- chyma of the lungs ; and we will have occasion, in treating of the functions of other parts, to refer again to the uses of elastic membranes and ligaments. The ligamenta subflava and the ligamentum nuchse are important in aiding to main- tain the erect position of the body and head, and to restore this position when flexion has been produced by muscular action. Still, the contraction of muscles is also necessary to keep the body in the vertical position. Muscular Movements. Muscular movements are observed only in the higher classes of animals. Low in the scale of animal life, we have the contractions of amorphous substance and ciliary mo- tion ; and in some vegetables, movements, even attended with locomotion, have been observed. These facts make the absolute distinction between the two kingdoms a question of some difficulty ; but in animals only do we have separate muscular systems. The muscular movements capable of being excited by stimulus of various kinds are divided into voluntary and involuntary ; and generally there is a corresponding divi- 1 See vol. i., Introduction, p. 91 9 ROBIN ET YERDEIL, Traite de chimie anatomique, Paris, 1853, tome iii., p. 364. 446 MOVEMENTS. sion of the muscles as regards their minute anatomy. The latter, however, is not absolute ; for there are certain invol- untary functions, like the action of the heart or the move- ments of deglutition, that require the rapid, vigorous con- traction characteristic of the voluntary muscular tissue ; and here we do not find the structure of the involuntary mus- cles. With a few exceptions, however, the anatomical division of the muscular tissue into voluntary and involun- tary is sufficiently distinct. Physiological Anatomy of the Involuntary Muscles.— We have so often described this tissue, as it is found in the vascular system, the digestive organs, skin, and other situ- ations, that it will not be necessary, in this connection, to give more than a sketch of its structure and mode of action. The involuntary muscular system presents a striking contrast to the voluntary muscles, not only in its minute anatomy and mode of action, but in the arrangement of its fibres. While the voluntary muscles are almost invariably attached by their two extremities to movable parts, the in- voluntary muscles form sheets or membranes in the walls of hollow organs, and by their contraction simply modify the capacity of the cavities which they enclose. Various names have been given to this tissue to denote its distribution, mode of action, or structure. The name involuntary muscle indicates that its contraction is not under the control of the will; and this is the fact, these muscles being chiefly animated by the sympathetic system of nerves, while the voluntary muscles are supplied mainly from the cerebro-spinal system. On account of the peculiar structure of these fibres, they have been called muscular fibre-cells, smooth muscular fibres, pale fibres, non-striated fibres, fusiform fibres, and contractile cells. The distribu- tion of these fibres to parts concerned in the organic or vegetative functions, as the alimentary canal, has given INVOLUNTARY MUSCLES. them the name of organic muscular fibres, or fibres of organic, or vegetative life. It is difficult to isolate the individual fibres of this tissue in microscopical preparations ; and when seen in situ, their borders are faint, and we can make out their arrangement best by the appearance of their nuclei. Robin recommends soaking the tissue for a few days in a mixture of one part of ordinary nitric acid to ten of water.1 This renders the fibres dark and granular, makes their borders very distinct, and frequently some of them become entirely isolated. The nuclei, however, are obscured. In their natural condition, the fibres are excessively pale, very finely granular, flat- tened, and of an elongated spindle-shape, with a very long, narrow, almost linear nucleus in the centre. The nucleus generally has no nucleolus, and it is sometimes curved, or shaped like the letter S. The ordinary length of these fibres is about -g-J-g-, and their breadth about ^nnnr °f an inch. In the gravid uterus they undergo remarkable hyper- trophy, measuring here from -§V to -^ of an inch in length, and 20*0 0 of an inch in breadth.8 The peculiarities of their structure in the uterus will be fully considered under the head of generation. In the contractile sheets formed of the involuntary mus- cular tissue, the fibres are arranged side by side, closely ad- herent, and their extremities, as it were, dove-tailed into each other. Generally the borders of the fibres are regular and their extremities simple; but sometimes the ends are forked, and the borders present one or more little projec- tions. It is very seldom that we see the fibres in a single layer, except in the very smallest arterioles. Usually the layers are multiple, being superimposed in regular order. The action of acetic acid is to render the fibres pale, so that their outlines become almost indistinguishable, and to bring 1 ROBIN, Recherches sur quelques particularites de la structure des capittaires de Fencephale. — Journal de la physiologic, Paris, 1859, tome ii., p. 541. 2 POUCHET, op. cit., p. 65. 448 MOVEMENTS. out the nuclei more strongly. If we have an indistinct sheet of this tissue in the field of view, the addition of acetic acid, by bringing out the long, narrow, and curved nuclei arranged in regular order, and rendering the fibrous and other structures more transparent, will often enable us to recognize its character. Contraction of the Involuntary Muscular Tissue. — The mode of contraction of the involuntary muscles is peculiar. It does not take place immediately upon the reception of a stimulus, applied either directly or through the nerves, but is gradual, enduring for a time and then followed by slow and gradual relaxation. A description of the peristaltic movements of the intestines gives a perfect idea of the mode of contraction of these fibres, with the gradual propagation of the stimulus along the alimentary canal, as the food makes its impression upon the mucous membrane.1 An equally striking illustration is afforded by labor-pains. These are due to the muscular contractions of the uterus, and last from a few seconds to one or two minutes.3 Their gradual access, continuation for a certain period, and gradual disap- pearance coincide exactly with the history of the contrac- tions of the involuntary muscular fibres. The strong points of contrast between the mode of action of the striated and the smooth muscular fibres are very well brought out in a recent paper by MM. Legros and Onimus. These observers, after carefully studying the structure and properties of the " muscles of vegetative life," give, in substance, the following resume of their physio- logical action : The contraction is slow, and the fibres return slowly to a condition of repose. The movements are always involun- tary. Peristaltic action is the rule ; and the contraction takes place progressively and without oscillations. Con- 1 See vol. ii., Digestion, p. 376, et seq. 2 CAZEAUX, A Theoretical and Practical Treatise on Midwifery, Philadelphia, 1857, p. 123. VOLUNTARY MUSCLES. 4:49 tractility persists for a long time after death. Arrest of function is followed by little or no atrophy, and hyper- trophy is very marked as the result of exaggerated action. Excitation of the nerves has less influence upon contraction of these fibres than direct excitation of the muscles. The involuntary muscular tissue is regenerated very rapidly, while the structure of the voluntary muscles is restored with great difficulty after destruction or division.1 Physiological Anatomy of the Voluntary Muscles. — A voluntary muscle is the most highly organized, and is possessed of the most varied endowments, of all living structures. It contains, in addition to its own peculiar contractile substance, fibres of inelastic and elastic tissue, adipose tissue, numerous blood-vessels, nerves, and lym- phatics, with certain nuclear and cellular anatomical ele- ments. The muscular system constitutes by far the greatest part of the organism, and its nutrition consumes a large pro- portion of the reparative material of the blood, while its clisassimilation furnishes a corresponding quantity. of excre- mentitious matter. The condition of the muscular system, indeed, is an almost unfailing evidence of the general state of the body, allowing, of course, for peculiarities in different individuals. Among the characteristic properties of the muscles are, elasticity, a constant and insensible tendency to contraction, called tonicity, the power of contracting forci- bly on the reception of a proper stimulus, called irritability, a peculiar kind of sensibility, and the faculty of generating galvanic currents. The relations of particular muscles, as taught by descriptive anatomy, involve special functions ; but the most interesting physiological points connected with this system relate to the general properties and functions of the muscles, and must necessarily be prefaced with a sketch of their general anatomy. 1 LEGROS ET OXIMUS, De la contraction des muscles de la vie vegetative. — Jour' nal de Tanaiomie, Paris, 1869, tome vi., p. 435. 29 450 MOVEMENTS. It has been demonstrated by minute dissection that all of the red, or voluntary muscles are made up of a great number of microscopic fibres, known as the primitive mus- cular fasciculi. These are called red, striated, or voluntary fibres, or the fibres of animal life. Their structure is com- plex, and they may be subdivided longitudinally into fibril- lae, and transversely into disks, so that it is somewhat doubtful as to what is, strictly speaking, the ultimate ana- tomical element of the muscular tissue. A primitive muscular fasciculus runs the entire length of the muscle, and is enclosed in its own sheath, without branching or inosculation. This sheath contains the true muscular substance only, and is not penetrated by blood- vessels, nerves, or lymphatics. If we view with the micro- scope a thin transverse section of a muscle, the divided ends of the fibres will present an irregularly polygonal form with rounded corners. They seem to be cylindrical, however, when viewed in their length and isolated. Their color by transmitted light is a delicate amber, resembling somewhat the color of the blood-corpuscles. The primitive fasciculi vary very much in size in dif- ferent individuals, and in the same individual under different conditions and in different muscles. As a rule they are smaller in young persons and in females than in adult males. They are comparatively small in persons of slight muscular development. In persons of great muscular vigor, or when the general muscular system or particular muscles have been increased in size and power by exercise, the fasciculi are relatively larger. It is probable that the physiological in- crease in the size of a muscle from exercise is due to an increase in the size of the preexisting fasciculi, and not to the formation of any new elements. In young persons the fasciculi are from 17100 to 12*00 of an inch in diameter. In the adult they measure from ^-J-0- to -^^ of an inch.1 The appearance of the primitive muscular fasciculi 1 LITTRE ET ROBIN, Dictionnaire de Medecine, Paris, 1865, Article, Musculaire. VOLUNTARY MUSCLES. 451 under the microscope is characteristic and unmistakable. They present regular transverse striae, formed of alternating dark and clear bands about 25^0() of an inch wide. These are generally very distinct in healthy muscles. In addition we frequently observe longitudinal striae, not so distinct, and quite difficult to follow to any extent in the length of the fasciculus, but tolerably well marked, particularly in muscles that are habitually exercised. The muscular sub- stance, presenting this peculiar striated appearance, is en- closed in an excessively thin but elastic and resisting tubular membrane, called the sarcolemma, or myolemma. According to Robin,1 the sarcolemma is composed of the same substance as the elastic tissue. This envelope cannot be seen in ordinary preparations of the muscular tissue ; but it frequently happens that the contractile muscular sub- stance is broken, leaving ths sarcolemma intact, which gives a good view of the membrane and conveys an idea of its strength and elasticity. Attached to the inner surface of the sarcolemma, are numerous small, elongated nuclei with their long diameter in the direction of the fasciculi. These are not usually well seen in the unaltered muscle, but the addition of acetic acid renders the muscular substance pale and destroys the striae, when the nuclei become very distinct. Water, after a time, acts upon the muscular tissue, ren- dering the fasciculi somewhat paler and larger. Acetic acid and alkaline solutions efface the striae, and the fibres become semitransparent. In fasciculi that are slightly decomposed, there is fre- quently a separation at the extremity into numerous smaller fibres, called fibrillae. These, when isolated, present the same striated appearance as the primitive fasciculus ; viz., alter- nate dark and light portions. They measure about 2g^o6 of an inch in diameter, and their number, in the largest primitive fibres, is estimated by Kolliker at about two thou- 1 Loc. tit. 452 MOVEMENTS. sand.1 The structure of the fibrillae, which are regarded by many as the anatomical elements of the muscular tissue, has been very closely studied by Rouget ; and, although all of his observations, particularly those with regard to the spiral form of the fibrillae, have not been confirmed, there can be hardly any doubt that their structure is uniform, the appear- ance of alternate dark and light segments being due to dif- ferences in thickness.2 In fact, it is well known that water, by its simple mechanical action, swells the fibrillge, and causes the striae to disappear. Late researches have shown that the interior of each prim- itive fasciculus is penetrated by an excessively delicate mem- brane, closely surrounding the fibrillse. This arrangement may be distinctly seen in a thin section of a fibre treated with a solution of salt in water in the proportion of five parts per thousand.3 The arrangement of this membrane, which is nothing more nor less than a series of tubular sheaths for the fibrillae, is a strong argument in favor of the view that the fibrilla is the anatomical element of the mus- cular tissue. By the action of certain reagents, such as alcohol, hydro- chloric acid, or gastric juice, the primitive fasciculi may be separated into disks corresponding to the transverse striae. Bowman, in his elaborate investigations into the structure of the muscles, noted this fact, and concluded that the cleav- age in this direction was as easily effected as the separation into fibrillae. He regarded the primitive fasciculi as com- posed of fibrillae, and these as made up of little particles, alternately dark and light, wrhich he called sarcous ele- ments.4 Subsequent investigations, however, have not en- 1 KOLLIKER, Elements tFhistologie humaine, Paris, 1868, p. 207. 2 ROUGET, Sur les phenomenes de polarization qui s'observent dans quelqucs tis- sus. — Journal de la physiologic, Paris, 1862, tome v., p. 263, et seq., and Memoire sur les tissus contractile^ et la contractilite. — Id., 1863, tome vi., p. 647, et scq, 3 KOLLIKER, Elements d}histologie humaine, Paris, 1868, p. 201. 4 BOWMAN, On the Minute Structure and Movements of Voluntary Muscle. — Philosophical Transactions, London, 1840, p. 457, et seq. VOLUNTAEY MUSCLES. 453 FIG. 16. tirely confirmed this view ; and the separation into disks is now pretty generally regarded as artificial. When we come to the question of the real anatomical element of the muscular tissue, there are only two reasonable yiews that present themselves. One is that all subdi- vision of the primitive fasciculus is artificial, and that it, with its investing membrane, the sarcolemma, is the true element. An ar- gument in favor of Voluntary muscular fibre*. A. Transverse striae and tlllS Opinion IS that nuclei of a primitive fasciculus (maeuified 250 di- ameters); B. Longitudinal stria? and fibrillse of a flip tissue is lllOSt read- primitive fasciculus in which the sarcolemma has l been lacerated at one point by pressure. (SAPPET, 1]^ ipnirfltpfl into "Pn«i- Traite d'anatomie, Paris, 1868, tome it, p. 22.) ciculi, each enclosed in its own membrane, and not penetrated by vessels, nerves, or lymphatics ; while the fibrillae are situated in a reticulum of canals, from which they cannot readily be isolated. The other opinion, that the fibrillse are the ultimate elements, is based on the fact that these little fibres present the striae and all the anatomical characteristics of the primitive fasciculi, and that by far the most natural and easy mode of separa- tion of these fasciculi is in a longitudinal direction. The question of adopting one or the other of these views is not of very great physiological importance. Fibrous and Adipose Tissue in the Voluntary Muscles. -The structure of the muscles strikingly illustrates the re- lations between the principal and the accessory anatomical elements of tissues. The characteristic or principal element 454: MOVEMENTS. is, of course, the muscular fibre or fibrilla ; but we also find in the substance of the muscles certain anatomical elements, not peculiar to the muscles, and merely accessory in their function, but none the less necessary to their proper consti- tution. For example, every muscle is composed of a number of primitive fasciculi ; but these are gathered into secondary bundles, which in turn are collected into bundles of greater and greater size, until, finally, the whole muscle is enveloped in its sheath, and is penetrated by a fibrous connective sub- stance. We find, probably, in the muscles, the best illustra- tion of the structure of what is known as the connective tissue. Connective Tissue. — We have already had occasion to refer to certain of the elements of connective tissue, more especially the inelastic and elastic fibres. In this connection we shall treat specially of the connective tissue of the mus- cles ; but our description will answer for almost all situations in which fibrous tissue exists merely for the purpose of hold- ing parts together. In the muscles we have a membrane holding a number of the primitive fasciculi into secondary bundles. This is known as the perimysium. The fibrous membranes that connect together these secondary bundles with their contents are enclosed in a sheath enveloping the whole muscle, sometimes called the external perimysium. The peculiarity of these membranes, and their distinction from the sarcolemma, is that they have a fibrous structure and are connected together throughout the muscle, while the tubes forming the sarcolemma are structureless, and each one is distinct. The name now most generally adopted for the tissue un- der consideration is connective tissue. It has been called cellular, areolar, or fibrous, but most of these names were given to it without a clear idea of its structure. Its prin- cipal anatomical element is a fibre of excessive, almost im- measurable, tenuity, wavy, and with a single contour. These VOLUNTARY MUSCLES. 4:55 fibres are collected into bundles of very variable size, and are held together by an adhesive amorphous substance. The wavy lines that mark the bundles of fibres give them a very characteristic appearance. The direction and arrangement of the fibres in the vari- ous tissues present marked differences. In the loose areolar tissue beneath the skin and between the muscles, and, in the loose structure surrounding some of the glands and connect- ing the sheaths of blood-vessels and nerves to the adjacent parts, the bundles of fibres form a large net-work, and are very wavy in their course. In the strong, dense membranes, as the aponeuroses, the proper coats of many glands, the periosteum and perichondrium, and the serous membranes, the waves of the fibres are shorter, and the fibres themselves interlace much more closely. In the ligaments and tendons, the fibres are more nearly straight, and are all arranged longitudinally. On the addition of acetic acid, the bundles of inelastic fibres swell up, become semitransparent, and the nuclei and elastic fibres are brought out. The proportion of elastic fibres differs very much in different situations, but they are all of the smallest variety, and present a striking contrast to the inelastic fibres in their form, and size. Though they are still very small, they always present a double contour. Certain cellular and nuclear elements are always found in the connective tissue. The cells have been described under the name of connective-tissue cells. They are very irregular in size and form, some of them being spindle-shaped or caudate, and others star-shaped. They possess one, and sometimes two or three clear, ovoid nuclei, with distinct nu- cleoli. On the addition of acetic acid the cells disappear, but the nuclei are unaffected. These are the fibro-plastic ele- ments of Lebert,1 and the embryo-plastic elements of Eobin.2 1 LEBERT, Physiologic pathologique, Paris, 1845, tome ii., page 120. 8 LITTBE ET ROBIN*, Didionnaire de medecine, Paris, 1865, Article, Embryo- plastique. 456 MOVEMENTS. It is impossible to give any accurate measurements of the cells, on account of their great variability in size. The length of the nuclei is from -g-gVo" to ^-^Vo- °f an inch, and their diameter, from -g^Vo" to ^Vo of an inch.1 The appear- ance of the connective tissue, with a few cells and nuclei, is represented in Fig. 1Y. FIG. 17. Loose net-work of connective tissue from the liaraan subject, showing the fibres and cells, a, a, a capillary blood-vessel. (ROLLETT, in STBICKER, Handbuch der Lehre von den Geweben, Leipzig, 1868, S. 57.) Between the muscles, and in the substance of the mus- cles between the bundles of fibres, there always exists a greater or less quantity of adipose tissue in the meshes of the fibrous structure. Blood-vessels and Lymphatics. — The muscles are abun- dantly supplied with blood-vessels, generally by a number of small arteries, with two satellite veins. The capillary ar- 1 ROBIN, loc. cit. VOLUNTARY MUSCLES. 457 rangement in this tissue is peculiar. From the smallest arterioles, capillary vessels are given off, arranged in a net- work with tolerably regular, oblong, rectangular meshes, their long diameter following the direction of the fibres. These envelop each primitive fasciculus, enclosing it com- pletely, the artery and vein being on the same side. The ca- pillaries are the smallest in the whole vascular system.. When distended with blood they are from -^Yo" to 31l$Q of an inch in diameter ; and when empty their diameter is from 7010() to -g-gVo °f an inch.1 The arrangement of the lymphatics in the muscles has never been definitely ascertained. There are numerous lym- phatics surrounding the large vascular trunks of the extremi- ties and of the abdominal and thoracic walls, which, it would appear, must come from the substance of the muscles ; but they have never been traced to their origin. Sappey has succeeded in injecting lymphatics upon the surface of some of the larger muscles, but never has been able to follow them into the muscular substance.3 Connection of the Muscles with the Tendons. — It is now generally admitted that the primitive muscular fasciculi terminate in little conical extremities, which are received into corresponding depressions in the bundles of fibres com- posing the tendons ; but this union is so close, that the muscle or the tendon may be ruptured without a separation at the point of juncture. In the penniform muscles this arrange- ment is quite uniform and elegant. In other muscles it is essentially the same, but the perimysium seems to be contin- uous with the loose areolar tissue enveloping the correspond- ing tendinous bundles. Chemical Composition of the Muscles. — We are as yet so little acquainted with the exact constitution of the nitrogen- ized constituents of the body, that we cannot appreciate the 1 KOLLIKER, Elements (Fhistologie humaine, Paris, 1868, p. 220. 2 SAPPEY, Traite cTanatomie descriptive, Paris, 1868, tome ii., p. 27. 458 MOVEMENTS. nature of all the proximate principles that exist in the mus- cular substance. The most important of these is musculine. This resembles the fibrin of the blood, but presents certain points of difference in its behavior to reagents, by which it may be readily distinguished. One of its peculiar properties is that it is dissolved at an ordinary temperature by a mix- ture of one part of hydrochloric acid and ten of water. The muscular substance is permeated by a fluid, called the muscular juice, which contains a peculiar coagulable principle called myosine. Combined with the organic principles, we find a great variety of mineral salts in the muscular substance, that can- not be separated without incineration. Certain excrementi- tious matters have also been found in the muscles ; and probably nearly all of those eliminated by the kidneys exist here, though they are taken up by the blood as fast as they are produced, and are consequently detected with difficulty. The muscles also contain inosite, inosic acid, lactic acid, and certain other acids of fatty origin. During life the muscular fluid is slightly alkaline, but it becomes acid soon after death. The muscle itself, during contraction, has an acid reaction.1 According to Gavarret, the muscular juice is alkaline or neutral after moderate exercise, as well as during complete repose ; but ne states that when a muscle is made to un- dergo excessive exercise, the lactic acid exists in greater quantity, and the reaction becomes acid.3 Physiological Properties of the Muscles. The general properties of the striated muscles, as distin- guished from all other tissues except the involuntary muscles, are as follows : 1. elasticity ; 2. tonicity ; 3. sensibility of a peculiar kind ; 4. contractility, or irritability. These are all necessary to the physiological action of the muscles. Their 1 BUDGE, Lehrbuch derspecieV.cn Physiologic des Memchen, Leipzig, 1862, S. 534. 2 GAVARRET, Les phenomenes physiques de la vie, Paris, 1869, p. 125. PHYSIOLOGICAL PROPERTIES OF THE MUSCLES. 459 elasticity is brought into play in opposing muscles or sets of muscles ; one set acting to move a part and extend the antagonistic muscles, which, by virtue of their elasticity, retract when the extending force is removed. Their tonicity is an insensible, and more or less constant contraction, by which the action of opposing muscles is balanced when both are in the condition of what we call repose. Their sensibil- ity is peculiar, and is expressed chiefly in the sense of fatigue, and in the appreciation of weight and resistance to contrac- tion. Their contractility, or irritability is the property which enables them to contract and exert a certain amount of mechanical force under the proper stimulus. All of these general properties strictly belong to physiology, as do some special acts that are not necessarily involved in the study of ordinary descriptive anatomy. Elasticity of Muscles. — The true muscular substance contained in the sarcolemma is eminently contractile ; and though it may possess a certain degree of elasticity, this property is most strongly marked in the accessory anatomi- cal elements. The interstitial fibrous tissue is loose and pos- sesses a certain number of elastic fibres, and, as we have seen, the sarcolemma is very elastic. It is probably the sar- colemma that gives to the muscles their retractile power after simple extension. It is unnecessary to follow out in detail all of the numer- ous experiments that have been made upon the elasticity of muscles. There is a certain limit, of course, to their perfect elasticity (understanding by this the degree of ex- tension that is followed by complete retraction), and this cannot be exceeded in the human subject without dislocation of parts. In some late experiments by Marey, it was found that the gaetrocnemius muscle of a frog, detached from the body, could be extended about one-fiftieth of an inch by a weight of a little more than three hundred grains. This weight, however, did not extend the muscle beyond the 460 MOVEMENTS. limit of perfect elasticity. The muscle of a frog of ordinary size was extended beyond the possibility of complete resto- ration by a weight of about seven hundred and fifty grains.1 Marey also showed that fatigue of the muscles increased their extensibility and diminished their power of subsequent retraction. This fact has its application to the physiological action of muscles ; for it is well known that they are un- usually relaxed during fatigue after excessive exertion ; and, as we should expect, they are at that time more than ordi- narily extensible. Muscular Tonicity. — The healthy muscles have an in- sensible and constant tendency to contract, which is more or less dependent upon the action of the motor nerves. If, for example, a muscle be cut across in a surgical operation, the divided extremities become permanently retracted ; or if the muscles be paralyzed on one side of the face, the mus- cles upon the opposite side insensibly distort the features. It is difficult to explain these phenomena by assuming that tonicity is due to reflex action, for there is no evidence that the contraction takes place as the consequence of a stimu- lus. All that we can say is, that a muscle, not excessively fatigued, and with its nervous connections intact, is con- stantly in a state of insensible contraction, more or less marked, and that this is an inherent property of all of the contractile tissues. Sensibility of the Muscles. — The muscles possess to an eminent degree that kind of sensibility which enables us to appreciate the powrer of resistance, immobility, and elasticity of substances that are grasped, on which, we tread, or which, by their weight, are opposed to the exertion of muscular power. It is by the appreciation of weight and resistance that we regulate the amount of force required to accomplish any muscular act. These properties refer chiefly to simple 1 MAREY, Du mouvement dans lesfondions de la vie, Paris, 1868, pp. 289, 301. MTJSCTJLAK CONTRACTILITY. 461 muscular efforts. After long-continued exertion, we appre- ciate a sense of fatigue that is peculiar to the muscles. It is difficult to separate this entirely from the sense of nervous exhaustion, but it seems to be, to a certain extent, distinct ; for when suffering from the fatigue that follows over-exer- tion, it seems as though we could send a nervous stimulus to the muscles, to which they are, for the time, unable to respond. When we come to consider fully the subjects of muscular and nervous irritability, we shall see that these two properties are entirely distinct, and that we may ex- haust or destroy the one without influencing the other. When the muscles are thrown into spasm or tetanic con- traction, a peculiar sensation is produced, entirely different from painful impressions made upon the ordinary sensitive nerves. In the cramps of cholera, tetanus, or the convul- sions from strychnine, these distressing sensations are very marked. The so-called recurrent sensibility of the anterior roots of the spinal nerves is probably due to the tetanic con- tractions produced by galvanizing these filaments. This question, however, will be taken up again in connection with the nervous system. If the muscles possess any general sensibility, it is very faint. A muscle may be lacerated or irritated in any way without producing actual pain, though we always can ap- preciate the contraction produced by irritants, and the sense of tension when the muscles are drawn upon. Muscular Contractility, or Irritability. — Physiologists now regard muscular irritability as synonymous with con- tractility ; and perhaps the latter term more nearly expresses the fact, though the term irritability, applied to the nerves, and even of late years to the glands, is one very generally used. By irritability we understand a property belonging to highly-organized parts, which enables them to perform cer- tain peculiar and characteristic functions in obedience to a proper stimulus. In the sense in which the term is gen- 462 MOVEMENTS. erally received, it is proper to apply it to any tissue or organ that performs its vital function, so-called, under a natural or artificial stimulus. The nerves receive impressions and carry a stimulus to the muscles, causing them to contract. This property, which is always present during life under normal conditions, and persists for a certain period after death, is called nervous irritability. It has lately been shown that the application of a proper stimulus will induce secretion by the glands ; and Bernard has called this glandular irritability.1 The application of a stimulus to the muscular tissue causes the fibres to contract ; and this is muscular irri- tability. As it always involves contraction, and is extinct only when the muscles can no longer act, it is equally proper to call this property contractility. 'No property, such as we understand by this definition of irritability, is manifested by tissues or organs that have purely passive or mechanical functions, such as bones, cartilages, and fibrous or elastic membranes. Irritability can only be applied properly to nerves or nerve centres, contractile structures, and glands. During life and under normal conditions, the muscles will always contract in obedience to a proper stimulus ap- plied either directly or through the nerves. In the natural action of the organism, this contraction is always induced by nervous influence through reflex action or volition. Still, a muscle may be living and yet have lost its contractility. For example, after a muscle has been for a long time par- alyzed and disused, the application of the most powerful galvanic excitation will fail to induce contraction. But when we examine such a muscle with the microscope, it is found that the nutrition has become profoundly affected, and that the contractile substance has disappeared, giving place to inert fatty matter. Muscular contractility persists for a certain time after death and in muscles separated from the body ; and this fact has been taken advantage of by phys- iologists in the study of the so-called vital properties of the 1 See page 24. MUSCULAR CONTRACTILITY. 463 muscular tissue. We have already seen that a muscle de- tached from the living body continues for a time to respire, and probably undergoes some of the changes of disassimila- tion observed in the organism. So long as these changes are restricted to the limits of physical and chemical integrity of the fibre, contractility remains. As these processes are very slow in the cold-blooded animals, the irritability of all the parts persists for a considerable time after death. We have repeatedly demonstrated muscular contractility, several days after death, in alligators and turtles. In the human subject and the warm-blooded animals, the muscles cease to respond to excitation a few hours after death, though the time of disappearance of irritability is very variable. Xysten, in a number of experiments upon the disappearance of contractility in the human subject after decapitation, found that different parts lost their con- tractility at different periods, but that generally this de- pended upon exposure to the air. With the exception of the right auricle of the heart, the muscles of the voluntary system were the last to lose their irritability. In one in- stance, certain of the voluntary muscles that had not been exposed retained their contractility seven hours and fifty minutes after death.1 The observations of Longet and Mas- son show that a galvanic shock, sufficiently powerful to pro- duce death, instantly destroys the irritability of the mus- cular tissue and of the motor nerves.2 One of the most important questions to determine with regard to muscular irritability is whether it be a property inherent in the muscular tissue or derived from the nervous system. The fact that muscles can be excited to more pow- erful and regular contractions by stimulating the motor nerves than by operating directly upon their substance and the great difficulty in tracing the nerves to their termination 1 XYSTEX, De la cotitractitite des organes musculaires. — Eecherches de physiologie et de chimie pathologiques, Paris, 1811, p. 306, et seg. 2 LOXGET, Tratte. de physiologie, Paris, 1869, tome ii., p. 602. 464 MOVEMENTS. in the muscles have led to the view that muscular contrac- tility is dependent upon nervous influence, and consequently that the muscles have no irritability or contractility, as a property inherent in their own substance. This doctrine, however, cannot be sustained. Bowman, in the course of his researches into the structure and movements of voluntary muscles, speaks of seeing the individual fibres contract after they had been isolated and removed from all connection with the nervous system ; and this has been frequently observed.1 The experiments of Longet, published in 1841, presented almost conclusive proof of the independence of muscular irritability. He resected the facial nerve, and found that it ceased to respond to mechanical and galvanic stimulus, or, in other words, lost its irritability, after the fourth day. Op- erating, however, upon the muscles supplied exclusively with filaments from this nerve, he found that they responded promptly to mechanical and galvanic irritation, and con- tinued to contract, under stimulation, for more than twelve weeks.8 In some further experiments it was shown that while the contractility of the muscles could be seriously in- fluenced through the nervous system, this was effected only by modifications in their nutrition. "When the mixed nerves were divided, the nutrition of the muscles was generally dis- turbed ; and although muscular irritability persisted for some time after the nervous irritability had disappeared, it be- came very much diminished at the end of six weeks. These experiments are very striking and satisfactory ; but the whole question was definitively settled by the observations of Bernard on the peculiar influence of the woorara poison and the sulphocyanide of potassium. As the result of these experiments, it was ascertained that some varieties of woorara destroy the irritability of the motor nerves, leaving the sen- sitive filaments intact. If a frog be poisoned by introducing 1 BOWMAN, The Minute Structure and Movements of Voluntary Muscle. — Philosophical Transactions, London, 1840, p. 488, et seq. 2 LONGET, Traite de physiologic, Paris, 1869, tome ii., p. 606. MUSCULAR CONTRACTILITY. 465 a little of this agent under the skin, irritation, galvanic or mechanical, applied to an exposed nerve, fails to produce the slightest muscular contraction ; but if the stimulus be applied directly to the muscles, they will contract vigorously. In this way the nerves are, as it were, dissected out from the muscles ; and the discovery of an agent that will paralyze the nerves, without affecting the muscles, is conclusive proof that the irritability of these two systems is entirely distinct. A curious effect of the woorara, that we may note in passing, is that in an animal under its influence, the muscular irrita- bility is intensified, and persists much longer after death than in animals not poisoned.1 If a frog be poisoned with sulpho- cyanide of potassium, precisely the contrary effect will be observed ; that is, the muscles will become insensible to ex- citation, while the nervous system is unaffected. This fact may be demonstrated by applying a tight ligature around the body in the lumbar region, involving all the parts except the lumbar nerves. If the poison be now introduced beneath the skin of the parts above the ligature, the anterior parts only are affected, because the vascular communication with the posterior extremities is cut off. If the exposed nerves be now galvanized, the muscles of the legs are thrown into con- traction, showing that the nervous irritability remains. Re- flex movements in the posterior extremities may also be pro- duced by irritation of the parts above the ligature.2 These experiments, most of which we have frequently re- peated, taken in connection with the observations of Longet, and the fact that isolated muscular fibres have been seen to contract, leave no doubt of the existence of an inherent and independent irritability in the muscular tissue. Contractions of muscles, it is true, are normally excited through the ner- vous system, and artificial stimulation of a motor or mixed nerve is the most efficient method of producing the simul- 1 BERNARD, Lemons sur Us e/ets des substances toxiyues et medicamentemes, Paris, 1857, pp. 277, 320, 353, 2 BERNARD, loc. oil., p. 354, et seq. 30 4:66 MOVEMENTS. taneous action of all the fibres of a muscle, or set of muscles ; but galvanic, mechanical, or chemical irritation of the mus- cles themselves will produce contraction, after the nervous irritability has been abolished. The conditions under which muscular irritability exists are simply those of normal nutrition of the muscular tissue. When the muscles have become profoundly affected in their nutrition, as the result of section of the mixed nerves, or after prolonged paralysis, the irritability disappears and cannot be restored. The determination of the presence or absence of muscular contractility, in cases of paralysis, is one of the methods of ascertaining whether treatment directed to the restoration of the nervous power will be likely to be followed by favorable results. If the muscular irritability have en- tirely disappeared, it is almost useless to attempt to restore the functions of the part. A great many experiments have been made upon the in- fluence of the circulation on muscular irritability, chiefly with reference to the effects of tying large vessels. Among the most recent are those of Longet. He tied the abdominal aorta in five dogs, and found that voluntary motion ceased in about a quarter of an hour, and that the muscular irrita- bility was extinct in two hours and a quarter. When the blood was restored, after three or four hours, by removing the ligature, the irritability and finally voluntary movement re- turned.1 These experiments show that the circulation of the blood is necessary to the contractility of the muscles. Tying the vena cava did not affect the irritability of the muscles. In dogs in which this experiment was performed, the lower extremities preserved their contractility, and the voluntary movements were unaffected up to the time of death, which took place in twenty-six hours.3 The relations of muscular irritability to the circulation have been further illustrated, in some very curious and in- 1 LONGET, Traite de physiologic, Paris, 1869, tome ii., p. 616. 2 LONGET, op. tit., p. 618. MUSCULAR CONTRACTILITY. 4:67 teresting experiments, by Dr. Brown-Sequard. The first observations were made upon two men executed by decapi- tation. Thirteen hours and ten minutes after death, when the muscular irritability had entirely disappeared and was succeeded by cadaveric rigidity, a quantity of fresh, defi- brinated, venous blood, from the human subject, was in- jected into the arteries of one hand, and returned by the veins. It was afterward reinjected several times during a period of thirty-five minutes. The whole time occupied in the different injections was from ten to fifteen minutes. Ten minutes after the last injection, and about fourteen hours after death, the irritability was found to have returned, in a marked degree, in twelve muscles of the hand. There were only two muscles out of the nineteen in which the irritability could not be demonstrated. Three hours after, the irritability still existed, but it disappeared a quarter of an hour later. The second observation was essentially the same, except that defibrinated blood from the dog was used, and the experiments were made upon the muscles of the arm. The irritability was restored in all of the muscles, and was present, the cadaveric rigidity having disappeared, twenty hours after decapitation.1 These experiments are exceedingly interesting, as showing the dependence of irritability upon certain of the processes of nutrition, which are probably restored, though temporarily and imperfectly, by the injection of fresh blood. They are also important in connection with the cadaveric rigidity of muscles, a condition which follows the loss of their so-called vital properties. The subject of cadaveric rigidity will be fully discussed as one of the phenomena of death. 1 BROWX-SEQUARD, Proprietes physiologiques et les usages du sang rouge et du sang noir. — Journal de la physiologic, Paris, 1858, tome i., p. 108, et seg. CHAPTEE XYI. MTJSCULAK COISTTEACTION. — PASSIVE OKGANS OF LOCOMOTION. Changes in the form of the muscular fibres during contraction — Secousse, Zuckung, or spasm — Spasm produced by artificial excitation — Mechanism of prolonged muscular contraction — Tetanus — Electric phenomena in the muscles — Muscular effort — Passive organs of locomotion — Physiological anatomy of the bones — Fundamental substance — Haversian rods — Haver- sian canals — Lacunse — Canaliculi — Bone-cells, or corpuscles — Marrow of the bones — Medullocells — Myeloplaxes — Periosteum — Physiological anat- omy of cartilage — Cartilage-cavities — Cartilage-cells — Fibro-cartilage. THE stimulus of the will, conveyed through the conduct- ors of motor influences from the brain to a muscle or set of muscles, produces an impression upon the muscular fibres and causes them to contract. In parts where the muscles have been exercised and educated, this action is regulated with ex- quisite nicety, so that the most delicate, rapid, as well as powerful contractions may be produced. Certain movements, not under the control of the will, are produced as the result of unconscious reflection from a nervous centre, along the motor conductors, of an impression made upon sensitive nerves. During this action, certain important phenomena are ob- served in the muscles themselves. They change in form, consistence, and, to a certain extent, in their constitution ; the different periods of their stimulation, contraction, and re- laxation are positive and well-marked ; their nutrition is for the time modified ; they develop galvanic currents ; and, in short, present a number of general phenomena, distinct from the results of their action, that are more or less interesting and important to the physiologist. MUSCULAR CONTRACTION. 469 The most striking of the phenomena accompanying mus- cular action is shortening and hardening of the fibres. It is only necessary to observe the action of any well-developed muscle to appreciate these changes. The active shortening is shown by the approximation of the points of attachment, and the hardening is sufficiently palpable. The latter phe- nomenon is marked in proportion to the development. of the true muscular tissue and its freedom from inert matter, such as fat. "We have already seen that it is the muscular sub- stance alone that has the property of contraction ; and we have shown that this action increases the consumption of oxygen and probably of other matters, the production of carbonic acid and some other excrementitious principles, and develops heat. Notwithstanding the marked and constant changes in the form and consistence of the muscles during contraction, the actual volume is unchanged, or it undergoes modifications so slight that they may practically be disregarded. Experi- ments on this point have been so uniform in their results, that it is hardly necessary to refer to them in detail. All modern observers accept the results of the older experiments in which muscles have been made to contract in a vessel of water connected with a small upright tube, showing that when the muscles are in active contraction as the result of a galvanic stimulus, the elevation of the liquid in the tube is unchanged. These old experiments have been recently repeated by Marey 1 and others, with more delicate and sen- sitive apparatus, and have been followed by the same results. It is evident, therefore, that a muscle, while it hardens and changes in form during contraction, does not sensibly change in its actual volume. 1 MAREY, Du mouvement dans ksfondions de la vie, Paris, 1868, p. 269. The earlier experiments of this kind were made by Glisson, Elaine, Carlisle, Barzel- lotti, Prevost, and Dumas, and some others. Prevost and Dumas used several large pieces of muscle, and their results were very satisfactory. (Memoire sur les phenomenes qui accompagnent la contraction de la fibre musculaire. — Journal de physiologic, Paris, 1823, tome iii., p. 310.) 470 MOVEMENTS. Changes in the Form of the Mitscular Fibres during Contraction. — It lias been found exceedingly difficult to de- termine a question apparently so simple as that of the change in form which the muscular fibres undergo during contrac- tion ; and it is only of late years that this single point has been definitively settled. The idea that the fibres do not shorten, but that they assume a zigzag arrangement during contraction, which was entertained by some of the earlier physiologists, and was supported very strongly by Prevost and Dumas,1 is not adopted by any modern writers. All are now agreed, that in muscular contraction there is an increase in the thickness of the fibre, exactly compensating its diminution in length. This has been repeatedly observed in microscopical exami- nations, by Bowman,3 Donne,3 and many others ; and the only points now to determine are the exact mechanism of this transverse enlargement, its duration, the means by which it may be excited, and its physiological modifica- 'tions. These questions, within the last few years, have been made the subjects of elaborate investigations by Helmholtz, Du Bois-Reymond, Aeby, Marey, and others ; and although it is hardly necessary to follow these experimenters through all of their investigations, many points have been developed, particularly by the system of registering the muscular move- ments, that possess considerable physiological importance. One essential condition in the study of the mechanism of muscular contraction is to imitate, in a muscle or part of a muscle that can be subjected to direct observation, the force that naturally excites it to contraction. The applica- tion of electricity to the nerve is beyond all question the most perfect method that can be employed for this purpose. We can in this way excite a single contraction, or, by em- ploying a rapid succession of currents, can excite continuous, 1 Journal de physiologic, Paris, 1823, tome iii., p. 301, et seq. 2 BOWMAN, On the Minute Structure and Movements of Voluntary Muscle. — Philosophical Transactions, London, 1840, p. 488. 3 DONNE, Cours de microscopie, Paris, 1844, p. 114. MUSCULAR CONTRACTION. 471 or tetanic action. While the electric current is not identi- cal with the nervous force, it is the best substitute we can employ in experiments on muscular contractility, and has the advantage of not affecting the physical and chemical integrity of the nervous and muscular tissue. In studying this subject, we will first follow some of the experiments upon muscular contraction excited artificially, and then apply them, as far as possible, to the strictly physiological actions of muscles. There are two classes of phenomena that may be pro- duced by electrical excitation of motor nerves: 1. When the stimulus is applied in the form of a single discharge, it is followed by a single muscular contraction. 2. Under a rapid succession of discharges, the muscle is thrown into a state of permanent, or tetanic contraction. It will greatly facilitate our comprehension of the subject to study these phenomena separately and successively. The muscular contraction produced by a single stimulus applied to the nerve is called, by the French, secousse (shock), and by the Germans, Zilckung (convulsion). It will be con- venient for us to employ some term that will express this sudden action of the muscular fibres, as distinguished from the contraction that takes place on repeated stimulation, or in continued muscular effort ; and we will designate a single muscular contraction, then, as spasm, applying the term tetanus, to continued action. Spasm Produced ~by Artificial Excitation. — If an elec- tric discharge, even very feeble, be applied to a motor nerve connected with a fresh muscle, it is followed by a sudden contraction, succeeded by a rapid relaxation. Under this stimulation, the muscle shortens by about three-tenths of its entire length.1 The form of the contraction, as registered by the apparatus of Helmholtz, Marey, and others who have applied the so-called graphic method to the study of muscu- 1 BECLARD, Traite elemental™ de physiologic, Paris, 1859, p. 507. 472 MOVEMENTS. lar action, presents certain interesting peculiarities. "We will give, however, only the general characters of this ac- tion, without discussing in detail the complicated apparatus employed.1 According to Helmholtz, the whole period of a single contraction and relaxation of the gastrocnemius muscle of a frog is a little less than one-third of a second. The muscles of mammals and birds contract more rapidly, but with this exception, the essential characters of the contraction are the same. The following are the periods occupied by these dif- ferent phenomena:2 Interval between stimulation and contraction 0"'020 Contraction 0"'180 Kelaxation 0"'105 0"-305 The duration of the electric current applied to the nerve is only 0"*0008. Contraction, however, does not follow im- mediately, there being an interval, called pose, of about one fiftieth of a second. The contraction then follows, suc- ceeded by gradual relaxation, the former being a little longer than the latter. This description represents the contraction of an entire muscle, but does not indicate the changes in form of the in- dividual fibres, a point much more difficult to determine satisfactorily. It is pretty well established, however, that a single fibre, with its irritability unimpaired, becomes con- tracted and swollen at the point where the stimulation is applied. Now, the question is whether, in normal contrac- tion of the fibres in obedience to the natural nervous stimulus, there be a uniform shortening of the whole fibre, a shortening of those portions only that are the seat of the 1 A very good resume of the general characters of a single muscular con- traction (secousse musculaire) is given by Bernard, in his recent work on the properties of living tissues. (Le$om sur les proprietes des tissus vivants, Paris, 1866, p. 193, et seq.) 2 BERNARD, op. cit., p. 196. MUSCULAR CONTRACTION. terminations of the motor nerves, or a peristaltic shortening and swelling, rapidly running the length of the fibre. The recent experiments of Aeby, which have been repeated and extended by Marey, demonstrate beyond a doubt that when one extremity of a muscle is excited, a contraction occurs at that point, and is propagated along the muscle in the form of a wave, exactly like the peristaltic action of the intestines, ex- cept that it is more rapid. Both Aeby and Marey have suc- ceeded in measuring the rapidity of this wave, and find it to be about forty inches per second.1 Applying this principle to the physiological action of muscles, Aeby advances the theory that shortening of the fibres takes place wherever a stimulus is received, and that this is propagated in the form of a wave, which meets in its course another wave starting from a different point of stimulation. As we know FIG. 18. Diagram of the muscular wave after Aeby. (MABEY, Du mouvement dans les fonctions de la vie, Paris, 1868, p. 282.) that the motor nerves terminate at different points by be- coming fused, as it were, with the sarcolemma, we can readily comprehend, under this theory, how the simultaneous con- traction of all the fibres of a muscle is produced by stimula- tion of its motor nerve. This idea is expressed in the ac- companying diagram. 1 MAREY, Du mouvement dans lesfonctions de la, vie, Paris, 1868, p. 280. 474: MOVEMENTS. Although this view of the physiological action of the muscular fibres is extremely probable, it cannot be assumed that it has been absolutely demonstrated ; but it is certainly more satisfactory and better sustained by experimental facts than any theory that has hitherto been advanced. Mechanism of prolonged Muscular Contraction. — By a voluntary effort we are able to produce a muscular contrac- tion of a certain duration, and of a power, within certain limits, proportionate to the amount of force we may desire to produce ; but after a certain time, the muscle becomes fa- tigued, and it may become exhausted to the extent that it will not respond to the normal stimulus. This is the kind of muscular action most interesting to us as physiologists. The experiments of Marey seem to show precisely how far the nervous action that gives rise to a powerful and con- tinuous muscular contraction can be imitated by electricity. Calling the movement produced by a single electric dis- charge, secousse, which we have translated by the word spasm, he calls the persistent contraction, tetanus. We will adopt this name to distinguish persistent muscular action from the single contraction that we have just described. It is a curious fact that a continued current of galvanic electricity passed through a nerve or a muscle does not induce muscular contraction; and it is only when the current is closed or broken that any action is observed. But if we employ statical electricity, a muscular spasm occurs at every discharge, proportionate, in some degree, to the power of the excitation. If the discharges be very frequently repeated, or if a galvanic current be applied, broken by an interrupting apparatus, the spasms follow each other in quick succession. In experimenting upon the muscles of the frog with a regis- tering apparatus, Marey has found that with a gradual increase in the rapidity of the electric shocks, the individual muscular spasms become less and less distinct, and that finally the contraction is permanent. His diagrams show MUSCULAR CONTRACTION. 475 well-marked spasms under ten excitations per second, a more complete fusion of the different acts with twenty per second, and a complete fusion, or tetanus, with twenty-seven per second. When the contraction had become continuous that was an elevation in the line, showing increased power, as the excitations became more and more frequent.1 This is precisely the kind of contraction that occurs in the physiological action of muscles. Although the ner- vous force is not by any means identical with electricity, either the interrupted galvanic current or a series of statical discharges is capable of producing a muscular action very like that which is involved in voluntary movements. The observations of Marey, showing that the intensity of what he terms artificial tetanic contraction is in proportion to the rapidity with which the electric discharges succeed each other, are exceedingly interesting in their practical applica- tions ; and an important question at once arises regarding the nervous force that excites voluntary motion. Is this a series of discharges, as it were, producing a power of mus- cular contraction in exact proportion to their rapidity ? In view of the experiments just cited, this theory is very prob- able ; and it is certain that a rapid succession of electric dis- charges almost exactly simulates the normal action. That vibrations, more or less regular, actually occur in muscular contraction has been settled beyond a doubt by the re- searches of Wollaston, Haughton, and more lately by Helm- lioltz, the latter having recognized a musical tone in con- tracting muscles, exactly corresponding with the number of impressions per second made upon the nerve. He further devised an ingenious method of recognizing the tone, by fill- ing the ears with wax and contracting the temporal and masseter muscles. Marey has found, in repeating this experiment, that the tone may be changed by modifying the intensity of the muscular action. With the jaws feebly con- tracted, a grave sound is produced, and this can be raised 1 MAREY, op. cit., p. 373, et seq 476 MOVEMENTS. one-fifth, by contracting the muscles as forcibly as pos- sible.1 The nerves are not capable of conducting an artificial stimulus for an indefinite period, nor are the muscles able to contract for more than a limited time upon the reception of such an impression. The electric current may be made to destroy for a time both the nervous and muscular irrita- bility ; these properties becoming gradually extinguished, the parts becoming fatigued before they are completely exhausted. Precisely the same phenomena are observed in the physiological action of muscles. When a muscle is fatigued artificially, a tetanic condition is excited more and more easily, but the intensity of the contraction proportion- ally diminishes.2 Muscles contracting in obedience to the will pass through the same stages of action. It is probable that constant contraction is excited more and more easily as the muscles become fatigued, because the nervous force is gradually diminishing in intensity. It is certain that the vigor of contraction at the same time progressively diminishes. Electric Phenomena in the Muscles. — It was ascertained a number of years ago, by Matteucci, that all living muscles are the seat of electric currents ; not very powerful, it is true, but still sufficiently marked to be detected by ordinary gal- vanometers. It is difficult, in the present state of our knowledge, to appreciate the physiological significance of this fact, and we will therefore merely allude to the chief electric phenomena that are ordinarily observed, without at- tempting to follow out the elaborate and curious experi- ments since made by Du Bois-Reymond and others. One of the most simple methods of demonstrating this current is to prepare the leg of a frog with the crural nerve attached, and apply one portion of the nerve to the deep parts of an incised muscle and the other to the surface. As soon as the connection is made, a contraction of the leg takes place. 1 MAREY, op. cit., p. 455. 2 Idem., p. 378, et scq. MUSCULAE EFFORT. 477 The same fact may be demonstrated with an ordinary gal- vanometer; but the evidence obtained by the frog's leg, when the experiment is properly performed, is sufficiently conclusive. Matteucci constructed out of the fresh muscles from the thigh of the frog, what is sometimes called a frog-battery ; which exhibits these currents in the most striking manner, their intensity being in direct ratio to the number of elements in the pile. To do this, he takes the muscles of the lower half of the thigh from several frogs, removing the bones, and arranges them in a series, each with its conical extremity inserted into the central cavity of the one below. In this way the external surface of each thigh except the last is in contact with the internal surface of the one below. If the two extremities of the pile be now connected with a gal- vanometer, quite a powerful current from the internal to the external surface of the muscle may be demonstrated. In a pile formed of ten elements, the needle of a galvanometer was deviated to from 30° to 40V ' Electric currents are observed in all living muscles, but are most marked in the mammalia and warm-blooded ani- mals. They exist, also, for a certain time after death. Artificial tetanus of the muscles, however, instead of intensi- fying the current, causes the galvanometer to recede. If, for example, the needle of the instrument show a deviation of 30° during repose, when the muscle is excited to tetanic contraction, it will return so as to mark only 10° or 15°. This phenomenon is observed only during a continued mus- cular contraction, and does not attend a single spasm. Muscular Effort. — The mere voluntary movement of parts of the body, when there is no obstacle to be overcome 1 MATTEUCCI, Lemons sur les phenomenes physiques dfs corps vivante, Paris, 1847, p. 175, et seq. For a fuller exposition of these interesting phenomena, the reader is referred to the elaborate treatise on physiology, by Prof. Longet (Traite de physiologic, Paris, 1869, pp. 620, 639). 478 MOVEMENTS. or no great amount of force is required, is very different from a muscular effort. For example, in ordinary progression there is simply a movement produced by the action of the proper muscles, almost without our consciousness, and this is unat- tended with any modification in the circulation or respira- tion; but if we attempt to lift a heavy weight, to jump, to strike a powerful blow, or to make any vigorous effort, the action is very different. In the latter instance, we prepare for the muscular action by inflating the lungs, closing the glottis, and contracting more or less forcibly the expiratory muscles, so as to render the thorax rigid and unyielding ; and by a concentrated effort of the will, the proper muscles are then brought into action. This remarkable action of the muscles of the thorax and abdomen, due to simple effort, and independent of the particular muscular act that is to be accomplished, compresses the contents of the rectum and bladder, and obstructs very materially the venous circulation in the large vessels. It is well known that hernia is frequently produced in this way; the veins of the face and neck be- come turgid ; the conjunctiva may become ecchymosed ; and sometimes aneurismal sacs are ruptured. An effort of this kind is generally of short duration, and cannot, indeed, be prolonged beyond the time during which respiration can be conveniently arrested. At its conclusion there is commonly a prolonged expiration, which is audible and somew;hat vio- lent at its commencement. There are degrees of effort which are not attended with this powerful action of the muscles of the chest and abdo- men, and in which the glottis is not completely closed ; and an opening into the trachea or larynx, rendering immobility of the thorax impossible, does not interfere with certain acts that require considerable muscular power. If we examine a dog with the glottis exposed, when he makes violent efforts to escape, we can see that the opening is firmly closed. This fact is indicated by Longet, and we have often observed it PASSIVE OK&ANS OF LOCOMOTION. 479 in vivisections ; but Longet has further shown 'that dogs with an opening into the trachea are frequently able to run and leap with " astonishing agility." He also saw a horse, with a large canula in the trachea, that performed severe labor and drew heavily-loaded wagons in the streets of Paris.1 Passive Organs of Locomotion. It would be out of place to describe fully and in detail all of the varied and complex movements produced by mus- cular action. Many of these, such as the movements of deg- lutition and of respiration, are necessarily considered in con- nection with the functions of which they form a part ; but others are purely anatomical questions. Associated and an- tagonistic movements, automatic and reflex movements, etc., belong to the history of the motor nerves, and will be fully considered under the head of the nervous system. The study of locomotion involves a knowledge of the physiological anatomy of certain passive organs, the bones, cartilages, and ligaments. Though a complete history of the structure of these parts trenches somewhat upon the domain of anatomy, we are tempted to give a brief description of their histology, as it will complete our account of the tissues of the body, with the exception of the nervous system and the organs of generation, which will be taken up hereafter. Locomotion is effected by the muscles acting upon cer- tain passive, movable parts. These are the bones, cartilages, ligaments, aponeuroses, and tendons. We have already de- scribed the fibrous structures, and it only remains for us to study the bones and cartilages. Physiological Anatomy of the Bones. — The number, clas- sification, and relations of the bones are questions belonging to descriptive anatomy ; and the only points we propose to consider refer to their general or microscopic structure. 1 LONGET, Traite de physiologic, Paris, 1869, tome ii., p. 669. 480 MOVEMENTS. Every bone, be it long or short, is composed of what is called the fundamental substance, marked by microscopic cavities and canals of peculiar form. The cavities contain corpuscular bodies, called bone-corpuscles. The canals of larger size serve for the passage of blood-vessels, while the smaller canals (canaliculi) connect the cavities with each other, and finally with the vascular tubes. Many of the bones present a medullary cavity, filled with a peculiar structure, called marrow. In almost all bones there are two distinct portions : one, which is exceedingly compact, and the other, more or less spongy or cancellated. The bones are also invested with a membrane, containing vessels and nerves, called the periosteum. The method usually employed in the study of the bones is by thin sections made in various directions, and examined either in their natural condition or with the calcareous mat- ter removed by maceration in weak acid solutions. By the first method, we can make out the relations of the funda- mental substance, the direction and relations of the vascular canals, and the form, size, relations, and connections of the bone-cavities and small canals. By the latter method we can isolate and study the organic and corpuscular elements. Fundamental Substance. — This constitutes the true bony substance, the medullary contents, vessels, nerves, etc., being simply accessory. It is composed of a peculiar organic mat- ter, called osteine, combined with various inorganic salts, in which the phosphate of lime largely predominates. In ad- dition to the phosphate of lime, the bones contain carbonate of lime, fluoride of calcium, phosphate of magnesia, soda, and the chloride of sodium. The relative proportions of the organic and inorganic matters are somewhat variable ; but the average is about one-third of the former to two-thirds of salts. This proportion is necessary to the proper consistence and toughness of the bones. Anatomically, the fundamental substance is arranged in the form of regular, concentric lamellae, about -^^ of an ANATOMY OF THE BONES. 481 inch in thickness.1 This matter is of an indefinitely and faintly-striated appearance, but it cannot be reduced to dis- tinct fibres. In the long bones the arrangement of the lamellae is quite regular, surrounding the Haversian canals, and forming what are sometimes called the Haversian rods, following in their direction the length of the bone. In the short, thick bones the lamellae are more irregular, frequently radiating from the central portion to the periphery. These peculiarities in the disposition of the fundamental substance will be more readily understood after a description of the Haversian canals. Haversian Canals. — These canals exist in the compact bony structure. They are absent, or very rare, in the spongy and reticulated portions. Their form is rounded or ovoid, the larger ones being sometimes quite irregular. In the long bones their direction is generally longitudinal, although they anastomose by lateral branches. Each one of these ca- nals contains a blood-vessel, and their disposition constitutes the vascular arrangement of the bones. They are all con- nected with the opening on the surface of the bones, by which the arteries penetrate and the veins emerge. Their size, of course, is variable. According to Sappey, the largest are about -fa and the smallest -g^-g- of an inch in diameter. Their average size is from -^-g- to -g-J-g- of an inch.a In a transverse section of a long bone the Haversian canals may be seen cut across and surrounded by from twelve to fifteen lamellae. In a longitudinal section the course and anasto- moses may be studied. Lacunae. — The fundamental substance is everywhere marked by irregular, microscopic excavations, of a peculiar form, called lacunae, or osteoplasts. These were at one time supposed to be corpuscles of calcareous matter, and were known as the bone-corpuscles ; but it has since been ascer- tained that this appearance is due to the imperfect methods 1 SAPPEY, Traite tfanatomie, Paris, 1866, tome i., p. 84. 2 SAPPEY, op. cit., p. 76. 31 482 MOVEMENTS. of preparation of the thin sections of bone. They are con- nected with numerous little canals, giving them a stellate appearance. These are most numerous at the sides. The lacunae measure from y^^rr to -g-J-g- of an inch in their long diameter, by about -^Vo °f an ^ncn *n width.1 They contain the true bone-corpuscles, which we will presently describe. Canaliculi. — These are little wavy canals, connecting the lacunae with each other and presenting a communication between the first series of lacunae and the Haversian canals. Each osteoplast presents from eighteen to twenty canaliculi radiating from its borders. Their length is from -^ to ^-J-g- of an inch, and their diameter about ^-g-^oir °f an inch.2 The arrangement of the Haversian canals, lacunae, and canaliculi is shown in Fig. 19. Fia. 19. Vascular canals and lacunae, seen in a transverse section of the dianhysis of the hn- merus. Magnified two htindred diameters.— 1, 1. 1, Section of the Haversian canals • 2, Section of a longitudinal canal divided at the point of its anastomosis with a transverse canal. Around the canals, cut across perpendicularly, are seen the lacunrc (with their canaliculi), forming concentric rings. (SAPPEY, Traite d'anatomie Paris 1866, tome i., p. 79.) .Bone-cells or Corpuscles. — By treating perfectly-fresh specimens of bone with weak acid solutions, Virchow has 1 SAPPEY, op. cit., p. 80. 2 Idem., p. 81. ANATOMY OF THE BOXES. 483 demonstrated the presence of stellate cells, or corpuscles, exactly filling up the lacunae, and sending prolongations into the canaliculi.1 These structures have since been studied by Rouget, who has succeeded in demonstrating them in fresh bones from the foetus, without using any reagent.2 They are stellate, granular, with a large nucleus and several nucleoli, and are of exactly the size and form of the lacunae. They send out prolongations into the canaliculi, but it has been impossible to ascertain positively whether or not they form membranes lining the canaliculi through their entire length. Marrow of the Bones. — The peculiar -structure called marrow is found in the medullary cavities of the long bones, filling them completely and moulded to all the irregulari- ties of their surface. It is also found filling the cells of the spongy portion. In other words, with the exception of the vascular canals, lacunaB, and canaliculi, the marrow fills all the spaces in the fundamental substance. We know very little of the functions of the marrow, and will therefore pass it over with a brief description. It is now settled that the cavities of the bones are not lined with a membrane corresponding to the periosteum, and that the marrow is applied directly to the bony substance. In the foetus and in very young children, the marrow is red and very vascular. In the adult it is yellow in some bones, and gray or gelatiniform in others. It contains certain pecu- liar cells and nuclei, with amorphous matter, adipose vesi- cles, connective tissue, blood-vessels, and nerves. Medullocells. — Robin has described little bodies, existing both in the form of cells and free nuclei, called medullocells. These are found in greater or less number in the bones at , Cellular Pathology, Philadelphia, 1863, p. 112. Virchow's first observations were made in 1850. 2 ROUGET, Note sur les corpuscles des os. — Journal de la physiologic, Paris, 1858, tome i., p. 764, etseq. 484: MOVEMENTS. all ages, but are more abundant in proportion as the amor- phous matter and fat-cells are deficient. The nuclei are spherical, with borders sometimes irregular, generally with- out nucleoli, finely granular, and from ^^Q-Q to -g-gVo of an inch in diameter. They are insoluble in acetic acid.1 The cells are less numerous than the free nuclei. They are spherical or slightly polyhedric, contain a few pale granu- lations, are rendered pale, but are not dissolved by acetic acid, and measure about 17100 of an inch in diameter.2 Myelopldxes. — These are irregular, nucleated patches, also described by Robin, more abundant in the spongy por- tions of the bones than in the medullary canals, and are applied to the internal surfaces of the bones. They are ex- ceedingly irregular in size and form (measuring from 12100 to -^Q of an inch in diameter), are finely granular, and pre- sent from two to twenty or thirty nuclei. The nuclei are clear, ovoid, generally with a nucleolus, and are from %^Q to innnr of an incn long> by -g^ to ^^ of an inch broad. The myeloplaxes are rendered pale by acetic acid, and the nuclei are then brought out more distinctly.8 In addition to the anatomical elements just described, the marrow contains a few very delicate bundles of connec- tive tissue, most of which accompany the blood-vessels. In the foetus the adipose vesicles are few or may be absent ; but in the adult they are quite numerous, and in some bones seem to constitute the whole mass of the marrow. They do not differ materially from the fat-cells in other situations. Holding these different structures together, is a variable quantity of semitransparent, amorphous, or slightly granu- lar matter. The nutrient artery of the bones sends branches to the marrow, generally two in number for the long bones, which are distributed between the various anatomical elements, and 1 LITTRE ET ROBIN, Dictionnaire demedecinc, Paris, 1865, Article, Medullocelle. 2 POUCHET, Precis d'histologie humaine, Paris, 1864, p. 106. 3 LITTRE ET ROBIN, Dictionnaire de medecine, Paris, 1865, Article, Myeloplaxe. ANATOMY OF THE BONES. 4:85 finally surround the fatty lobules and the fat-vesicles with a delicate capillary plexus. The veins correspond to the arte- ries in their distribution. The nerves follow the arteries, and are lost when these vessels no longer present a muscular coat.1 Nothing is known of the presence of lymphatics in any part of the bones, or in the periosteum. The only point of physiological interest connected with the marrow is, that it has been found to possess, in common with the periosteum, but in a less degree, the property of generating true bony substances. TVe shall see further on, that the periosteum is not only very important to the nutrition of the bones, but that it will generate bone when transplanted into vascular parts. M. Oilier, who has made a very extended series of experiments upon the physiological properties of the periosteum, endeavored to produce bone by transplanting portions of marrow, but was unsuccessful. M. Goujon, however, has lately been more fortunate. He has found that frequently, but not always, marrow trans- planted into the muscular tissue will generate bone, particu- larly the marrow taken from young bones, but the bony tissue thus formed is soon absorbed.3 Periosteum. — In most of the bones the periosteum pre- sents a single layer of fibrous tissue ; but in some of the long bones two or three layers may be demonstrated. This mem- brane adheres to the bone, but can generally bs separated without much difficulty. It covers the bones completely, except at the articular surfaces, where its place is supplied by cartilaginous incrustation. It is composed mainly of fibres of the white inelastic variety, with numerous small elastic fibres, blood-vessels, nerves, and a few adipose vesicles. The arterial branches ramifying in the periosteum are 1 SAPPET, op. czV., p. 95. 2 GOUJOX, Recherches experimentales sur les proprieles physiologiqiies de la moelle des os. — Journal de T anatomic, Paris, 1869, tome vi., p. 399, el seq. 486 MOVEMENTS. quite numerous, forming a close, anastomosing plexus, which sends numerous small branches into the bony substance. There is nothing peculiar in the arrangement of the veins. The distribution of the veins in the bony substance has been very little studied. The nerves of the periosteum are very abundant, and form in its substance quite a close plexus. The adipose tissue is very variable in quantity. In some parts it forms a continuous sheet, and in others the vesicles are scattered here and there . through the substance of the membrane. The importance of the periosteum to the nutrition of the bones is very great. Instances are on record where bones have been removed, leaving the periosteum, in which the entire bone has been regenerated. The importance of the periosteum has been still further illustrated by the remark- able experiments of M. Oilier, upon transplantation of this membrane in the different tissues of living animals.1 Physiological Anatomy of Cartilage. — In this connec- tion the structure of the articular cartilages presents the chief physiological interest. The articular surfaces of all the bones are encrusted with a layer of cartilage, varying in thickness from -fa to -^ of an inch. The cartilaginous sub- stance is white, opaline, and semitransparent when examined in thin sections. It is not covered with any membrane, but in the non-articular cartilages it has an investment analo- gous to the periosteum. Examined in thin sections, cartilage is found to consist of a homogeneous fundamental substance, marked with numerous excavations, called cartilage-cavities, or chondro- plasts. The intervening substance has a peculiar organic 1 The original memoirs of M. Oilier were published in the Journal de la phys- iologie, Paris, 1859-1863, tome ii., pp. 1, 169, 468, tome iii., p. 88, tome iv., p. 87, tome v., p. 59, and tome vi., pp. 466, 517. He has since published an elabo- rate work on the subject, in two volumes. (Traite experimentale et dinique de la generation des os, Paris, 1867.) ANATOMY OF CARTILAGE. 48T FIG base, called cartilagine. By prolonged boiling this is changed into a new substance, called chondrine. The or- ganic matter is united with a certain proportion of inorganic salts. This fundamental substance is elastic and resisting. The cartilages are closely united to the subjacent bony tis- sue. The free articular surface has already been described.1 Cartilage- Cavities. — These cavities are round- ed or ovoid, measuring from Y^VF to -g-J-g of an inch in diameter.2 They are generally smaller in the articular cartilages than in other situations, as in the costal carti- lages. They are simple excavations in the funda- mental substance, have no lining membrane, and contain a small quantity of a viscid liquid, with one or more cells. They are entirely analogous to the lacunse of the bones. Cartilage -Cell s. — Xear the surface of the articular cartilages the cavities contain each a single cell; -but in the gection of a diarttaodiai cartilage; deeper portions the cav- ities are long and con- tain from two to twenty cells arranged longitu- dinally. The cells are of about the size of the smallest 1 See page 40. 2 POUCHET, Precis tfhistologie humaine, Paris, 1864, p. 117- 488 MOVEMENTS. cavities. They are ovoid, with, a large, granular nucleus. They often contain a few small globules of oil. In the costal cartilages the cavities are not numerous, but are rounded and quite large. The cells contain generally a certain amount of fatty matter. The appearance of the or- dinary articular cartilage is represented in Fig. 20. The ordinary cartilages have neither blood-vessels, lym- phatics, nor nerves, and are nourished exclusively by imbibi- tion from the surrounding parts. Their function has already been sufficiently considered in treating of the synovial mem- branes. In the development of the body, the anatomy of the cartilaginous tissue possesses peculiar interest, from the fact that the deposition of cartilage precedes the formation of bone ; but we have here only to do with the permanent cartilages. Fibro-Cartilage. — This variety of cartilage presents cer- tain important peculiarities in the structure of its funda- mental substance. It exists in the synchondroses, the car- tilages of the ear, of the Eustachian tabes, the interarticular disks, the intervertebral cartilages, the cartilages of Santorini and of Wrisberg, and the epiglottis. Its structure has been very closely and successfully studied by Sappey, who has arrived at results differing considerably from those obtained by other observers. According to Sappey,1 the fibre-cartilage is composed of true fibrous tissue with a great predominance of elastic fibres, fusiform, nucleated fibres, a certain number of adipose vesi- cles, cartilage-cells, and numerous blood-vessels and nerves. The presence of cartilage-cells assimilates this tissue to the ordinary cartilage, though its structure is very much more complex. The fibrous elements above mentioned take the place of the homogeneous fundamental substance of the true cartilage. The most important peculiarity in the structure of this tissue is that it is abundantly supplied with blood- vessels and nerves. 1 SAPPEY, Traite tfanatomie, Paris, 1867, tome i., p. 458, et seq. ANATOMY OF CARTILAGE. 489 The reader is referred to works upon anatomy for a his- tory of the action of the muscles. In some works upon physiology, will be found descriptions of the acts of walking, running, leaping, swimming, etc. ; but we have thought it better to omit these subjects, rather than to enter as mi- nutely as would be necessary into anatomical details, and to give elaborate descriptions of movements, so simple and familiar. CHAPTER XVII. VOICE AND SPEECH. Sketch of the physiological anatomy of the vocal organs — Vocal chords — Mus- cles of the larynx — Crico-thyroid muscles — Arytenoid muscle — Lateral crico-arytenoid muscles — Thyro-arytenoid muscles — Mechanism of the pro- duction of the voice — Appearance of the glottis during ordinary respira- tion— Movements of the glottis during phonation — Variations in the quality of the voice, depending upon differences in the size and form of the larynx and the vocal chords — Action of the intrinsic muscles of the larynx in phonation — Action of the accessory vocal organs — Mechanism of the dif- ferent vocal registers — Mechanism of speech. THERE are few subjects connected with human physiology of greater interest than the mechanism of voice and speech. In common with most of the higher classes of animals, man is endowed with voice ; but, in addition, he is able to express, by speech, the ideas that are the result of the working of the brain. In this regard there is a difference between man and all other animals. It is the remarkable development and the peculiar properties of the brain that enable him to acquire the series of movements that constitute articulate language ; and this faculty is always impaired pari passu with deficiency in the intellectual endowment. Language is one of the chief expressions of intelligence ; and its study, in itself, constitutes almost a distinct science, inseparably connected with psychology. In connection with the study of movements, therefore, it is not necessary to discuss the origin and construction of language, but simply to indicate the mechanism, first, of the formation of the voice, and PHYSIOLOGICAL ANATOMY OF THE YOCAL ORGANS. 4:91 afterward the manner in which the voice is modified so as to admit of the production of articulate sounds. The voice in the human subject, presenting, as it does, a variety of characters as regards intensity, pitch, and quality, and susceptible of great modifications by habit and culti- vation, affords a very extended field for physiological study. Of late years this has been the subject of careful investiga- tion by the most eminent physicists and physiologists ; but to follow it out to its extreme limits requires a knowledge of the physics of sound and the theory of music, a full con- sideration of which would be inconsistent with the scope and objects of this work. AVe shall content ourselves, there- fore, with a sketch of the physiological anatomy of the parts concerned in the formation of the voice, and the mechanism by which sounds are produced in the larynx, without treat- ing fully of their varied modifications in quality. It will not be necessary to treat of the different theories of the voice that have been presented from time to time, except in so far as they have been confirmed by more recent and complete observations, particularly those in which the vocal organs have been studied in action by means of the laryngoscope. Sketch of the Physiological Anatomy of the Vocal Organs. The principal organ concerned in the production of the voice is the larynx. The accessory organs are the lungs, trachea, and expiratory muscles, and the mouth and reso- nant cavities about the face. The lungs furnish the air by which the vocal chords are thrown into vibration, and the mechanism of this action is only a modification of the pro- cess of expiration. By the action of the expiratory muscles the intensity of vocal sounds is regulated. The trachea not only conducts the air to the larynx, but, by certain varia- tions in its length and calibre, may assist in modifying the pitch of the voice. Most of the variations in the tone and quality, however, are effected by the action of the larynx itself and the parts situated above it. 492 VOICE AND SPEECH. It is impossible to give a complete account of the structure of the larynx, without going more fully than is desirable into purely anatomical details. Some anatomical points have already been referred to under the head of respiration, in connection with the respiratory movements of the glottis ; 1 and we propose here only to refer to the situation of the vocal chords, and to indicate the modifications that they can be made to undergo in their relations and tension by the action of certain muscles. The vocal chords are stretched across the superior open- ing of the larynx from before backward. They consist of two pairs. The superior, called the false vocal chords, are not concerned in the production of the voice. They are less prominent than the inferior chords, though they have nearly the same direction. They are covered by an excessively thin mucous membrane, which is closely adherent to the sub- jacent tissue. The chords themselves are composed of fibres of the white inelastic variety, mixed with a few elas- tic fibres. The true vocal chords are situated just below the superior chords. Their anterior attachments are near together, at the middle of the thyroid cartilage, and are immovable. Pos- teriorly they are attached to the movable arytenoid carti- lages ; and by the action of certain muscles, their tension may be modified, and the chink of the glottis may be opened or closed. These ligaments are much larger than the false vocal chords, and contain a very great number of elastic fibres. Like the superior ligaments, they are covered with an excessively thin and closely adherent mucous membrane. According to M. Fournie, the author of a very elaborate and recent work on the voice, the mucous membrane over the borders of the chords is covered with pavement-epithelium, without cilia.2 There are no mucous glands in the mem- brane covering either the superior or the inferior chords. 1 See vol. i., Respiration, p. 358. 2 FOURNIE, Physiologie de la voix et de la parole, Paris, 1866, p. 129. MUSCLES OF THE LAKY^X. 493 It has been conclusively shown, particularly by the ex- periments of Longet, that the inferior vocal chords are alone concerned in the production of the voice. This author, who has made numerous experiments on phonation, has demon- strated, by operations on dogs, that the epiglottis, the supe- rior vocal chords, and the ventricles of the larynx, may be injured, without producing any serious alteration jn the voice ; but that phonation becomes impossible after serious lesion of the inferior chords.1 This being the fact, as far as the mere production of the voice in the larynx is con- cerned, we have only to study the mechanism of the action of the inferior ligaments and the muscles by which their tension and relations are modified. Muscles of the Larynx. — Anatomists usually divide the muscles of the larynx into extrinsic and intrinsic. The ex- trinsic muscles are attached to the outer surface of the larynx and to adjacent organs, such as the hyoid bone and the sternum. They are concerned chiefly in its movements of elevation or depression. The intrinsic muscles are attached to the different parts of the larynx itself, and, by their action upon the articulating cartilages, are capable of modifying the condition of the vocal chords. The number of the in- trinsic muscles is nine, four pairs and a single muscle. In studying the situation and attachments of these muscles, it will be useful at the same time to note their mode of action. This has been experimentally demonstrated by Louget, who has studied the isolated action of the different muscles by galvanizing the nervous filament distributed to each one, either in the living animal, or in animals recently killed. In this way he has been able to show the mechanism of dila- tation of the larynx during inspiration, and to indicate the precise action by which the vocal chords are rendered tense or are relaxed.3 These experiments, by the positive charac- 1 LOXGET, Traite de physiologic , Paris, 1869, tome ii., p. 728, et seq. 8 Op. cit., p. 727. VOICE AND SPEECH. tcr of their results, have done much to simplify the study of the muscular acts concerned in the production of the voice. Bearing in mind the relations and attachments of the vocal chords, we can understand precisely how they can be rendered tense or loose by muscular action. Their fixed point is in front, where their extremities, attached to the thyroid cartilage, are nearly or quite in contact with each other. The arytenoid cartilages, to which they are attached posteriorly, present a movable articulation with the cricoid cartilage ; and the cricoid, narrow in front, and wide behind, where the arytenoid cartilages are attached, presents a mov- able articulation with the thyroid cartilage. It is evident, therefore, that muscles acting upon the cricoid cartilage can cause it to swing upon its two points of articulation with the inferior cornua of the thyroid, raising the anterior portion and approximating it to the lower edge of the thyroid ; and, as a consequence, the posterior portion, which carries the arytenoid cartilages and the posterior attachments of the vocal chords, is depressed. This action would, of course, in- crease the distance between the arytenoid cartilages and the anterior portion of the thyroid, elongate the vocal chords, and subject them to a certain degree of passive tension. Experiments have shown that such an effect is produced by the contraction of the cri co-thyroid muscles. The articulations of the different parts of the larynx are such that the arytenoid cartilages may be approximated to each other posteriorly, though perhaps only to a slight extent, thus diminishing the interval between the posterior attachments of the vocal chords. This action can be effected by contraction of the single muscle of the larynx, the aryte- noid, and also by the lateral crico-arytenoid muscles. The thyro-arytenoid muscles, the most complicated of all the in- trinsic muscles in their attachments and the direction of their fibres, according to Longet, give rigidity and increased capacity of vibration to the vocal chords.1 1 Op. tit., p. 730. MUSCLES OF THE LARYNX. 495 The posterior crico-arytenoid muscles, arising from each lateral half of the posterior surface of the cricoid cartilage, passing upward and outward to be inserted into the outer angle of the inferior portion of the arytenoid cartilages, rotate these cartilages outward, separate them, and act as dilators of the chink of the glottis. These muscles are chiefly concerned in the respiratory movements during in- spiration. The muscles mainly concerned in the modifications of the voice by their action upon the vocal chords are the crico- thyroids, the arytenoid, the lateral crico-arytenoids, and the thyro-arytenoids. The following is a sketch of their attach- ments and mode of action : Crico-thyroid Muscles. — These muscles are situated on the outside of the larynx at the anterior and lateral por- tions of the cricoid cartilage. Each muscle is of a triangular form, the base of the triangle looking posteriorly. It arises from the anterior and lateral portions of the cricoid cartilage, and its fibres diverge to be inserted into the inferior border of the thyroid cartilage, extending from the middle of this border posteriorly, as far back as the inferior cornua. Longet, after dividing the nervous filaments distributed to these mus- cles, noted hoarseness of the voice, depending upon relaxation of the vocal chords ; and by imitating its action mechanically, he approximated the cricoid and thyroid cartilages in front, carried back the arytenoid cartilages, and rendered the chords tense.1 Arytenoid Muscle. — This single muscle fills up the space between the two arytenoid cartilages and is attached to their posterior surface and borders. Its evident action is to approximate the posterior extremities of the chords and constrict the glottis, as far as the articulations of the arytenoid cartilages with the cricoid will permit. In any event, this muscle is important in phonation, as it serves to fix the posterior attachments of the vocal chords and 1 LONGET, loc. dt. 496 VOICE AND SPEECH. to increase the efficiency of certain of the other intrinsic muscles.1 Lateral Crico-arytenoid Muscles. — These muscles are situated in the interior of the larynx. They arise from the sides and superior borders of the cricoid cartilage, pass upward and backward, and are attached to the base of the arytenoid cartilages. By dividing all of the filaments of the recurrent laryngeal nerves except those distributed to these muscles, and then galvanizing the nerves, Longet has shown that they act to approximate the vocal chords and constrict the glottis, particularly in its interligamentous portion.2 These muscles, with the arytenoid, act as constrictors of the larynx. Thyro-arytenoid Muscles. — It is sufficiently easy to indi- cate the relations and attachments of these muscles, but their mode of action is more complex and difficult of comprehen- sion. When we come to study the conditions of the vocal chords involved in certain modifications of the voice, we will refer more in detail to the action of different fasciculi of these muscles. In this connection we will only describe very briefly their situation and attachments, and the general results of their contraction. The thyro-arytenoid muscles are situated within the larynx. They are broad and flat, and arise in front from the upper part of the crico-thyroid membrane and the lower half of the thyroid cartilage. From this line of origin, each muscle passes backward in two fasciculi, both of which are attached to the anterior surface and outer border of the arytenoid cartilages. The application of galvanism to the nervous filaments distributed to these muscles has the effect 1 A very interesting case of aphonia, reported by Dr. Knight, of Boston, in which the appearances were carefully studied with the laryngoscope, seems to show that the arytenoid muscle is not capable of producing any considerable amount of movement, in totality, of the arytenoid cartilages. (KNIGHT, Two Cases of Paralysis of Intrinsic Muscles of the Larynx. — Boston Medical and Sur- gical Journal, 1869, New Series, vol. in., p. 49, et seq.) 2 LONGET, loc. tit. PRODUCTION OF THtf VOICE. 497 of rendering the vocal chords rigid and increasing the in- tensity of their vibrations.1 The great variations that may be produced in the pitch and quality of the voice by the action of muscles operating directly or indirectly on the vocal chords render the problem of determining the precise mode of action of the intrinsic muscles of the larynx exceed- ingly complicated and difficult. It is certain, however, that, in these muscular acts, the thyro-arytenoids play an impor- tant part. Their contraction regulates the thickness and rigidity of the vocal chords, while at the same time it modi- fies their tension. Fournie regards the swelling of the chords, which may be rendered regular and progressive under the influence of the will, as one of the most important agents in the formation of the tones of the voice.3 Mechanism of the Production of the Voice. It will save much unprofitable discussion to dismiss quite briefly most of the theories that have been advanced to explain the production of the voice, and to avoid com- parisons of the larynx with different kinds of musical instru- ments. Before the larynx had been studied in action by means of the laryngoscope, physiologists, having the anatom- ical structure of the parts for their only guide, presented various speculations with regard to the mechanism of phona- tion, which were frequently utterly opposed to each other in principle. The vocal apparatus was compared to wind or brass instruments, to reed-instruments, to string-instruments, to the flute, etc., and some even refused to the vocal chords any share in the sonorous vibrations. An apparatus was de- vised to imitate the vocal organs, experiments were made with the larynx removed from the body, and every thing seemed to be done, except to observe the organs in actual function.3 1 LONGET, op. cit., p. 730. 2 FOURNIE, Physiologic de la voix et de la parole, Paris, 1866, p. 121. 3 Perhaps the most elaborate of the observations made before the discovery of the laryngoscope are those of J. Miiller, who experimented very extensively 32 498 VOICE AND SPEECH. A short time, however, after the laryngoscope came into use, the larynx was examined during the production of vocal sounds. The true value of previous theories was then positively demonstrated ; and while it has not been possible to settle all disputed points with regard to the precise mode of action of certain muscles, the appearances of the larynx itself during phonation and the results of the action of cer- tain of the intrinsic muscles have been quite accurately described. One of the first elaborate series of investigations of the subject by means of tLje laryngoscope was made by Manuel Garcia.1 These observations were chiefly directed to the changes of the glottis in singing, and were made by Garcia upon his own person. The essential points devel- oped by these experiments have since been confirmed by Battaille,2 and many other observers. Appearance of the Glottis during Ordinary Respiration. — If the glottis be examined with, the laryngoscope during ordinary respiration, the wide opening of the chink during inspiration, due to the action of the crico-arytenoid muscles, can be observed without difficulty. This action is effected by a separation of the posterior points of attachment of the vocal chords to the arytenoid cartilages. During ordinary expiration, none of the intrinsic muscles seem to act, and the larynx is entirely passive ; while the air is gently forced out by the elasticity of the lungs and of the thoracic walls. But as soon as an effort is made to produce a vocal sound, the ap- pearance of the glottis undergoes a remarkable change, and becomes modified in the most varied and interesting man- ner, with the different changes in pitch and intensity that with artificial vocal apparatus and with the larynx itself removed from the body. Many of the ideas of Miiller have been carried out by recent laryn- goscopic researches (Manuel de physiologic, Paris, 1851, p. 127, el seq.). 1 GARCIA, Observations on the Human Voice. — Proceedings of the Royal Society, London, 1856, vol. vii., p. 399, et scq. 2 BATTAILLE, Nouvellcs recherches sitr la phonation. — Comptes rendus, Paris, 1861, tome Hi., p. 716, et scq. PRODUCTION OF THE VOICE. 499 the voice can be made to assume. Although it is suffi- ciently evident that a sound may be produced, and even that words may be articulated with the act of inspiration, true and normal phonation is effected during expiration only. It is evident, also, that the inferior vocal chords are the only ones concerned in the act. The changes in the position and tension of the chords we shall study, first with reference to the general act of phonation, and after- ward as the chords act in the varied modifications of the voice, as regards intensity, pitch, and quality. Movements of the Glottis during Phonation. It is somewhat difficult to observe with the laryngoscope all of the vocal phenomena, on account of the epiglottis, which hides a considerable portion of the vocal chords ante- riorly, especially during the production of certain tones; but the patience and skill of Garcia enabled him to over- come most of these difficulties, and to settle, by autolaryngo- scopy, the most important questions with regard to the move- ments of the larynx in singing. It is fortunate that these ob- servations, which are models of scientific accuracy and the re- sult of most persevering study, were made by one profoundly versed, theoretically and practically, in the knowledge of music, and possessed of great control over the vocal organs.1 Garcia, after having observed the respiratory movements of the larynx, as we have briefly described them, noted that as soon as any vocal effort was made, the arytenoid carti- lages were approximated, so that the glottis appeared as a narrow slit, formed by two chords of equal length, firmly attached posteriorly as well as anteriorly. The glottis thus 1 Manuel Garcia, the author of these observations, is the son of Garcia, the great composer and singer, and the brother of Mme. Malibran. He now enjoys a great reputation in London, as a singing-master ; and his experiments were made with a view, if possible, of reducing the art of singing, which had always been taught according to purely empirical methods, to scientific accuracy. It is evident that this could be accomplished only through an exact knowledge of the mechanism of the production of vocal sounds. 500 VOICE AND SPEECH. undergoes a marked change. A nearly passive organ, open- ing widely for the passage of air into the lungs, because the inspiratory act has a tendency to draw its edges together, and entirely passive in expiration, it has now become a sort of musical instrument, presenting a slit with borders capable of accurate vibration. The approximation of the posterior extremities of the vocal chords and their tension by the action of certain of the intrinsic muscles are accomplished just before the vocal effort is actually made. The glottis being thus prepared for the emission of a particular sound, the expiratory muscles force air through the larynx with the required power. It seems wonderful how a carefully-trained voice can be modu- lated and varied in all its qualities, including the intensity of vibration, which is so completely under control ; but when we consider the changes in its quality, we must remember, in explanation, the varying conditions of tension and length of the vocal chords, the differences in the size of the larynx, trachea, and vocal passages generally, and the different relations that the accessory vocal organs can be made to assume. The power of the voice is simply due to the force of the expiratory act, which is regulated chiefly by the antag- onistic relations of the diaphragm and the abdominal muscles. From the fact that the diaphragm, as an active inspiratory muscle, is exactly opposed to the muscles which have a ten- dency to push the abdominal organs, with the diaphragm over them, into the thoracic cavity, and thus diminish the pulmonary capacity, the expiratory and inspiratory acts can be balanced so nicely that the most delicate vocal vibrations can be produced. It is unnecessary to refer more in detail to the action of these muscles, as we have already treated of this subject fully in another volume.1 The glottis, thus closed as a preparation to a vocal act, presents a certain amount of resistance to the egress of air. This is overcome by the action of the expiratory muscles, 1 See vol. i., Respiration, p. 385, et seq. PRODUCTION OF THE VOICE. 501 and with the passage of air through the chink, the edges of the opening, which are formed by the true vocal chords, are thrown into vibration. Many of the different qualities that are recognized in the human voice are due to differ- ences in the length, breadth, and thickness of the vibrat- ing ribbons ; but, aside from what is technically known as quality, the pitch is dependent chiefly upon the length of the opening through which the air is made to pass, and the degree of tension of the chords. The mechanism of these changes in the pitch of vocal sounds is well illustrated by Garcia in the following passage, which relates to what is known as the chest-voice : 1 " If we emit veiled and feeble sounds, the larynx opens at the notes p/jiv ^^1, and we see the glottis agitated by r *~~j [ d large and loose vibrations throughout do, re, mi. its entire extent. Its lips comprehend in their length the anterior apophyses of the arytenoid cartilages and the vocal chords ; but, I repeat it, there remains no triangular space. " As the sounds ascend, the apophyses, which are slightly rounded on their internal side, by a gradual apposition com- mencing at the. back, encroach on the length of the glottis ; and as soon as we reach the sounds pi? ~], thev fin- i VT, I ' v ish by touching each other through- ESzzzztzzEij out their whole extent ; but their summits are ^ do. onV s°l~ idly fixed one against the other at the notes p^jr-- ^ . In some organs these summits are a little bLj!__^_^j:z3 vacillating when they form the posterior do, re. end of the glottis, and two or three half-tones which are formed show a certain want of purity and strength, which is very well known to singers. From P-J2- i the vi- brations, having become rounder and EfcSi 1—^3 purer, 9J £&' are accomplished by the vocal liga- do, re. ments alone, up to the end of the register. 1 GARCIA, op. cit., p. 401. We have indicated the notes in the following paragraphs by the method most commonly used by musicians, as is done by Mrs. Seiler, in the same quotation. 502 VOICE AND SPEECH. " The glottis at this moment presents the aspect of a line swelled toward its middle, the length of which diminishes still more as the voice ascends. We shall also see that the cavity of the larynx has become very small, and that the superior ligaments have contracted the extent of the ellipse to less than one-half." These observations, have been in the main confirmed by Battaille,1 Emma Seiler,8 and all who have applied the la- ryngoscope to the study of the voice in singing. A few years ago we had an opportunity of observing the changes in th'e form of the glottis during the production of vocal sounds of different degrees of pitch, through the kindness of Dr. Ephraim Cutter, of Boston. In these experiments the various points to which we have alluded were illustrated by autolaryngoscopy in the most marked manner ; and nothing could be more striking than the changes in the form of the glottis in the transition from low to high notes. We have also frequently observed the general appearance of the glottis in phonation in experiments upon animals in which the glottis has been exposed to view. Variations in the Quality of the Voice, depending upon differences in the Size and Form of the Larynx and the Vocal Chords. — We are all sufficiently familiar with the characters of the male as distinguished from the female voice, and what are known as the different vocal registers. In childhood, the general characters of the voice are essen- 1 Loc. cit. 2 EMMA SEILER, TJie Voice in Singing, translated from the German, Phila- delphia, 1868. This little work contains the results of a series of observations on the voice, made after the method employed by Garcia. These are peculiarly interesting, as they are applied particularly to the study of the female voice, and elucidate certain disputed points with regard to the production of the fal- setto and the head-voice. The whole subject of the voice is treated in an eminently scientific manner, and the author professes to correct many faults in the methods of teaching the art of singing, that have had their origin in the employment of purely empirical methods. PRODUCTION OF THE VOICE. 503 tially the same in both sexes. The larynx is smaller than in the adult, and the vocal muscles are evidently more feeble ; but the quality of the vocal sounds at this period of life is peculiarly pure and penetrating. While there are peculiari- ties that distinguish the voices of boys before the age of puberty, they present, as in the female, the different quali- ties of the soprano and contralto. At this age the voices of boys are capable of considerable cultivation, and their pecu- liar quality is sometimes highly prized in church-music. After the age of puberty, the female voice does not com- monly undergo any very marked change, except in the de- velopment of additional strength and increased compass, the quality remaining the same ; but in the male there is a rapid change at this time in the development of the larynx, and the voice assumes an entirely different quality of tone. This change does not usually take place if castration be performed in early life ; and this barbarous operation was frequently resorted to in the seventeenth century, for the purpose of preserving the qualities of the soprano and contralto, par- ticularly for church-music. It is only of late years, indeed, that this practice has fallen into disuse in Italy. The ordinary range of all varieties of the human voice is given by Miiller as equal to nearly four octaves ; but it is rare that any single voice has a compass of more than two and a half octaves. There are examples, however, in which singers have acquired a compass of three octaves, and even more. The celebrated singer, Mme. Parepa-Rosa, has a compass of voice that touches three full octaves, from so!2 to sol5. In music, the notes are written the same for the male as for the female voice, but the actual value of the female notes, as reckoned by the number of vibrations in the second, is always an octave higher than the male.1 In both sexes there are differences, both in the range and the quality of the voice, which it is impossible for a culti- vated musical ear to mistake. In the male, we have the 1 FOURXIE, Physiologic de la voix et de la parole, Paris, 1866, p. 531. 504: VOICE AND SPEECH. bass and the tenor, with an intermediate voice, called the barytone. In the female, we have the contralto and the soprano, with the intermediate, or mezzo-soprano. In the bass and barytone, the lower and middle notes are the most natural and perfect; and while the higher notes may be acquired by cultivation, they are not easy, and do not possess the same quality as the corresponding notes of the tenor. The same remarks apply to the contralto and soprano. The mezzo-soprano is regarded by many as an artificial division. The following scale, proposed by Miiller, gives the ordi- nary ranges of the different kinds of voice ; but it must be remembered that there are individual instances in which these limits are very much exceeded : 1 CONTRALTO 1 mi fa sol la si do re mi fa sol la si do re mi fa sol la si do re mi fa sol la si do 11 111 22 2'2 2223333 333444444 There is really no great difference in the mechanism of these different kinds of voice, and the differences in pitch are due chiefly to the greater length of the vocal chords in the low-pitched voices, and their shortness in the higher voices. The differences in quality are due to peculiarities in the conformation of the larynx, to differences in its size, and in the size and form of the auxiliary resonant cavities. Great changes in the quality of the voice may be effected by practice. A cultivated note, for example, has an entirely different sound from a harsh, irregular vibration ; and, by practice, a tenor may imitate the quality of the bass, and vice versa, although the effort is unnatural. It is not at all unusual to hear male singers imitate very closely the notes 1 MUELLER, Manuel de physiologic, Paris, 1851, tome ii., p. 198. PRODUCTION OF THE VOICE. 505 of the female, and the contralto will sometimes imitate the voice of the tenor in a surprisingly natural manner. These facts have a somewhat important bearing upon certain dis- puted points with regard to the mechanism of the different vocal registers, which will be considered further on. Action of the Intrinsic Muscles of the Larynx in Pho- nation. — It is much more difficult to find an entirely satis- factory explanation of the different tones produced by the human larynx in the action of the intrinsic muscles than to describe the changes in the tension and relations of the vocal chords. These muscles are concealed from view, and the only idea that we can have of their action is by reasoning from a knowledge of their points of attachment, and by oper- ations upon the dead larynx, either imitating the contrac- tion of special muscles or galvanizing the nerves in animals recently killed. In this way, as we have seen, some of the muscular acts have been studied very satisfactorily ; but the precise effect of the contraction of certain of the muscles, particularly the thyro-arytenoids, is still a matter of dis- cussion. In the production of low chest-tones, in which the vocal chords are elongated and at the minimum of tension that will allow of regular vibrations, the crico-thyroid muscles are undoubtedly brought into action, and are assisted by the arytenoid and the lateral crico-arytenoids, which combine to fix the posterior attachments of the vibrating ligaments. It will be remembered that the crico-thyroids, by approximat- ing the cricoid and thyroid cartilages in front, have a ten- dency to remove the arytenoid cartilages from the anterior attachment of the chords. As the tones produced by the larynx become higher in pitch, the posterior attachments of the chords are approxi- mated more firmly, and at this time the lateral crico-aryte- noids are probably brought into vigorous action. The function of the thyro-arytenoids is more complex ; 506 VOICE AND SPEECH. and it is probably in great part by the action of these mus- cles that the varied and delicate modifications in the rigidity of the vocal chords are produced. The remarkable differences in singers in the purity of their tones are undoubtedly due in greatest part to the un- swerving accuracy with which some put the vocal chords upon the stretch ; while in those in whom the tones are of inferior quality, the action of the muscles is more or less vacillating, and the tension is frequently incorrect. The fact that some celebrated singers can make their voice heard above the combined sounds from a large chorus and orchestra is not due entirely to the intensity of the sound, but in a great measure to the absolute mathematical equality of the sonorous vibrations, and the comparative absence of discord- ant waves.1 Musicians who have heard the voice of the celebrated basso, Lablache, all bear testimony to the re- markable quality of his voice, which could be heard at times above a powerful chorus and orchestra. A grand illustration of this occurred at the musical festival at Boston, in 1869. In some of the solos by Mine. Parepa-Rosa, accompanied by a chorus of nearly twelve thousand, with an orchestra of more than a thousand and largely composed of brass instru- ments, we distinctly heard the pure and just notes of this remarkable soprano, standing alone, as it were, against the entire choral and instrumental force ; and this in an im- mense building containing an audien.ce of forty thousand persons. The absolute accuracy of the tone was undoubt- edly an important element in its remarkably penetrating 1 Immense progress has been made in the analytical study of different sounds by the celebrated German physicist, Hehnholtz. By means of his in- geniously-constructed resonators, taking advantage of the laws of consonance, in accordance with which the quality as well as the pitch of different tones is reproduced, he has been able to separate sounds into their different component parts as accurately as a ponderable compound is resolved into its constituent elements in the laboratory of the chemist. — (HELMHOLTZ, Theorie physiologique de la musique fondee sur V etude des sensations auditives, Paris, 1868, p. 48, etseq.) This subject will be fully considered under the head of audition. ACTION OF THE ^ACCESSORY VOCAL OEGANS. 507 quality. In the same way we explain the fact that the flute, clarinet, or the sound from a Cremona violin, may be heard soaring above the chords of a full orchestra. Action of the Accessory Vocal Organs. — A correct use of the accessory organs of the voice is of the greatest im- portance in singing ; but the manner in which these parts perform their function is exceedingly simple, and does not require a very extended description. The human vocal organs, indeed, consist of a vibrating instrument, the larynx, and certain tubes and cavities by which the sound is reen- forced and modified. The trachea serves not only to conduct air to the larynx, but to reenforce the sound to a certain extent by the vibra- tions of the column of air in its interior. When a powerful vocal effort is made, it is easy to feel, with the finger upon the trachea, that the air contained in it is thrown into vibra- tion. The structure of this tube is such that it may be elongated and shortened at will. In the production of low tones, the trachea is shortened and its calibre is increased, the reverse obtaining in the higher notes of the scale. Coming to the larynx itself, we find that the capacity of its cavity is capable of certain variations. In fact, both the vertical and the bilateral diameters are diminished in the high notes and increased in low tones. The vertical diame- ter may be modified slightly by ascent and descent of the true vocal chords, and the lateral diameter may be reduced by the inferior constrictors of the pharynx, acting upon the sides of the thyroid cartilage. The epiglottis, the superior vocal chords, and the ventri- cles are by no means indispensable to the production of vo- cal sounds. In the formation of high tones, the epiglottis is somewhat depressed, and the superior chords are brought nearer together ; but this only affects the character of the resonant cavity above the glottis. In low tones the su- perior chords are separated. It was before the use of the 508 VOICE AND SPEECH. laryngoscope in the study of vocal phenomena that the epiglottis and the ventricles were thought to be so important in phonation. Undoubtedly the epiglottis has something to do with the character of the voice ; but its function in this regard is not absolutely necessary, or even very important, as has been clearly shown by Longet in his experiments of excising the part in living animals.1 The most important modifications of the laryngeal sounds are produced by the resonance of air in the pharynx, mouth, and nasal fossae. This resonance is indispensable to the production of the natural human voice. Under ordinary conditions, in the production of low notes the velum palati is fixed by the action of its muscular fibres, so that there is a reverberation of the bucco-pharyngeal and naso-pharyngeal cavities ; that is, the velum is in such a position that neither the opening into the nose or the mouth is closed, and all of the cavities resound. As the tones are raised, the isthmus contracts, the part immediately above the glottis is also con- stricted, the resonant cavity of the pharynx and mouth is reduced in size, until finally, in the highest tones of the chest-register, the communication between the pharynx and the nasal fossse is closed, and the sound is reenforced entirely by the pharynx and mouth. At the same time the tongue, a very important organ to singers, particularly in the pro- duction of high notes, is drawn back into the mouth. The point being curved downward, its base projects upward pos- teriorly, and assists in diminishing the capacity of the cav- ity. In the changes which the pharynx thus undergoes in the production of different tones, the uvula acts with the velum and assists in the closure of the different openings. In singing up the scale, this is the mechanism, as far as the chest-tones extend. When, however, we pass into what is known as the head-voice, the velum palati is drawn forward instead of backward, and the resonance takes place chiefly in the naso-pharyngeal cavity. 1 LONGET, Traite de physiologic, Paris, 1869, tome ii., p. 727. VOCAL REGISTERS. 509 Mechanism of the different Vocal Registers. — There has been a great deal of discussion, even among those who have studied the voice with the laryngoscope, with regard to the exact mechanism of the different vocal registers. It is now pretty well settled how the ordinary tones of what is known as the chest-register are produced ; but with regard to the falsetto, the difficulties in the way of direct observation are so great, that the question of its mechanism cannot be said to be definitively established. The following are the vocal registers now recognized by most physiologists : 1. The chest-register, most powerful in male voices and in contraltos, and, indeed, almost characteristic of the male. 2. The falsetto register, which is the most natural voice of the soprano ; though this voice is capable of chest-tones, not so full, however, as in the contralto or in the male. In the female this is known as the middle register. 3. The head-register, produced by a peculiar action of the glottis and the resonant cavities above the larynx. This is cultivated particularly in tenors and in the female. Aside from the three registers, which belong to every voice, a practised ear can find no difficulty in distinguishing the different voices in nearly any part of the scale, both in the male and the female, by the following peculiarities : In the bass the low tones are full, natural, and powerful, and the higher tones nearly always seem more or less artificial. In singing, the passage from the natural to the artificial tones in the scale is generally more or less apparent. In the tenor the full, natural tones are higher in the scale, the lower tones being almost always feeble and wanting in roundness. Corresponding peculiarities enable us to distin- guish between the contralto and the soprano. Chest-Register. — We will simply recapitulate briefly the mechanism of the chest-tones, to enable us to study more easily the transitions to the different upper registers. This 510 VOICE AND SPEECH. is the voice commonly used in speaking, and is the most nat- ural, the vocal ligaments vibrating according to their ten- sion, as the air is forced through the larynx from the chest, and the air in the pharynx, mouth, and nasal fossae pro- ducing a resonance without any artificial division of the different cavities. As the tones are elevated the vocal chords are simply rendered more tense, and the parts above the larynx are more or less constricted, without any other change in the mechanism of the sound. But the chest-voice in the male cannot pass certain well-defined limits ; and in the very highest notes it must be merged, either into the head-voice or the falsetto. The falsetto, however, is now but little cultivated, though some tenor singers, after long practice, succeed in making the change from one register to the other so nicely that it is hardly perceptible, even to a cultivated ear. The head-voice has essentially the same mechanism in the male as in the female, and will be consid- ered after we have discussed the falsetto, which is the natu- ral voice of soprano singers. Falsetto Register. — The difference of opinion among laryngoscopists with regard to the mechanism of the falsetto is probably in great part due to the fact that when these tones are produced, the isthmus of the fauces is so power- fully contracted that it becomes exceedingly difficult to study the action of the vocal chords. There is no reason for supposing that the mechanism of this register does not involve vibration of the true vocal chords, as in the chest-voice, the difference being in the tension and in the extent of the vibrating portion. According to the observa- tions of Fournie, in the falsetto the tongue is pressed strongly backward and the epiglottis is forced over the larynx.1 Mrs. Emma Setter, from an extended series of autolaryngoscopic observations, has arrived at the conclu- sion that this voice involves vibrations of the fine, thin edges 1 Op. dt., p. 463. VOCAL REGISTEKS. 511 of the chords only, a greater width vibrating in the produc- tion of the chest-voice. She is particularly careful to insist upon the distinction between the falsetto and the head- register, the latter being produced by an entirely different mechanism.1 On the whole, this explanation seems to be the most satisfactory. It must be remembered that the distinction between the chest-register or the head-register and the falsetto, as far as pitch is concerned, is not absolute. Certain of the high notes of the chest or the head-voice, for example, may be produced in the falsetto. In the cultivation of the female voice, Mrs. Seller considers that it is exceedingly important not to strain the chest-voice to its highest point, but to use each register in its normal place in the scale, taking care, by practice, to render the transition from one to the other natu- ral and agreeable. We have heard male singers, probably endowed with peculiar vocal powers, who were able, by the use of the falsetto, to imitate almost exactly. the soprano voice, though without the sweetness and purity of tone char- acteristic of the perfect female organ. In the same way, by straining the chest-voice beyond its normal limits, some fe- males, particularly contraltos, are able to produce a very- good imitation of the tenor quality. Head- Register. — This voice is highly cultivated, particu- larly in tenors and in the best female singers. It is not to be confounded, however, with the falsetto, as was done by some physiologists, before the invention of the laryngoscope.2 Head-tones may be produced by cultivated male singers, bass and barytone, as well as tenor ; but the former seldom have occasion for any but the chest-notes. Still, there are musical passages in which the sotto-voce head-notes of the bass have an exquisite softness, and are used with great effect. Mrs. Seiler has studied this voice by autolaryngo- 1 EMMA SEILER, The Voice in Singing, Philadelphia, 1868, p. 56, ft seq. • MUELLER, Manuel de physiologic, Paris, 1851, tome ii., p. 199. 512 VOICE AND SPEECH. scopy with the greatest success, and has confirmed her views with regard to the mechanism of its production by numerous observations upon other singers. We have already stated that Fournie has shown that, in the transition to the head-voice, the velum palati is applied to the base of the tongue, and the sound is reenforced by resonance from the naso-pharyngeal cavity.1 If this be its mechanism, its study with the laryngoscope must be exceedingly difficult. The most important theory of the mechanism of the head-voice has been proposed by Mrs. Seiler. After long and patient effort, she was able to expose the glottis during the production of these tones, when it was found that the vocal chords were firmly approximated posteriorly, leaving an oval opening, with vibrating edges, involving only one- half or one-third of the vocal ligaments. This orifice con- tracted progressively with the higher tones. This peculiar division of the vocal ligaments is due, according to Mrs. Seiler, to the action of a muscular bundle, called the inter- nal thyro-arytenoid, upon little cartilages, the cuneiform, extending forward from the arytenoid cartilage, in the sub- stance of the vocal ligaments, as far as the middle of the glottis.3 "With proper cultivation, the transition from the middle re- gister to the head- voice in the female may be effected almost imperceptibly, thereby increasing the compass from three to six tones, and even more ; and in the male the same may be accomplished without difficulty, particularly in tenors. There can be hardly any doubt of the fact that the naso-pharyngeal space is chiefly concerned in the resonance that takes place in head-tones, though its actual demonstration is very difficult. The distinction between the head and the chest-notes is fully as marked in the male as in the female ; but it must be remembered that one of the great ends to be accomplished in the cultivation of the human voice is to make the three 1 FOURNIE, op. cit., p. 421. 2 Op. cit., p. 60. MECHAXISM OF SPEECH. 513 registers pass into each other so that they shall appear as one.1 Mechanism of Speech. Articulate language consists in a conventional series of sounds made for the purpose of conveying certain ideas. There being no universal language, we must confine our description of the faculty of speech to the mode of produc- tion of the language in which this work is written. Lan- guage, as it is naturally acquired, is purely imitative, and does not involve of necessity the construction of an alphabet, with its combinations into syllables, words, and sentences ; but as civilization has advanced, we have been taught to associate certain differences in the accuracy and elegance with which ideas are expressed, with the degree of development and cultivation of the intellectual faculties. Philologists have long since established a certain standard, varying, to some extent, it is true, with usage and the advance of knowledge, but still sufficiently definite, by which the correctness of modes of expression is measured. We do not propose to discuss the science of language, or to consider, in this connection, at least, the peculiar mental operations concerned in the expression of ideas, but to take our own tongue as we find it, and describe briefly the mechanism of the production of the most important articu- late sounds. Almost every language is imperfect, as far as an exact correspondence between its sounds and written characters is concerned. Our own language is full of incongruities in spelling, such as silent letters and arbitrary and unmeaning 1 In studying the mechanism of the voice in singing, we have received great assistance in many practical points from Mme. Parepa-Rosa, to whose remark- able power as a vocalist we have already alluded, and Sig. A. Bendelari, of this city, the eminent singing-master. These distinguished artists, thoroughly skilled both in the science as well as the art of music, have elucidated several difficult questions, by their practical knowledge of the art of blending and modi- fying the different vocal registers. 33 514 VOICE AND SPEECH. variations in pronunciation ; but these do not belong to the subject of physiology. There are, however, certain natural divisions of the sounds as expressed by the letters of the alphabet. Vowels. — Certain articulate sounds are called vowel, or vocal, from the fact that they are produced by the vocal chords, and are but slightly modified as they pass out of the mouth. The true vowels, a, e, i, o, u, can all be sounded alone, and may be prolonged in expiration. These are the sounds chiefly employed in singing. The differences in their characters are produced by changes in the position of the tongue, mouth, and lips. The vowel-sounds are neces- sary to the formation of a syllable, and although they are generally modified in speech by consonants, each one may, of itself, form a syllable or a word. In the construction of syllables and words, the vowels have many different quali- ties, the chief differences being as they are made long or short. In addition to the modifications in the vowel-sounds by consonants, two or three may be combined so as to be pronounced by a single vocal effort, when they are called respectively, diphthongs and triphthongs. In the proper diphthongs, as oi, in voice, the two vowels are sounded. In the improper diphthongs, as ea, in heat, and in the Latin diphthongs, as se, in Caesar, one of the vowels is silent. In triphthongs, as eau, in beauty, only one vowel is sounded. Y, at the beginning of words, is usually pronounced as a con- sonant ; but in other situations it is pronounced as e or i. Consonants. — Some of the consonants have no sound in themselves, and only serve to modify vowel-sounds. These are called mutes. They are b, d, k, p, t, and c and g hard. Their office in the formation of syllables is sufficiently apparent. The consonants known as semi-vowels are, f, 1, m, n, r, s, and c and g soft. These have an imperfect sound of MECHAOTSM OF SPEECH. 515 themselves, approaching in character the true vowel-sounds. Some of these, 1, m, n, and r, from the facility with which they flow into other sounds, are called liquids. Orthoepists have further divided the consonants with reference to the mechanism of their pronunciation : d, j, s, t, z, and g soft, being pronounced with the tongue against the teeth, are called dentals ; d, g, j, k, 1, n, and q are called palatals ; b, p, f, v, and m are called labials ; m, n, and ng are called nasals ; and k, q, and c and g hard are called gutturals.1 After the full description we have given of the voice, it is not necessary to discuss further the mechanism of these sim- ple acts of articulation. For the easy and proper production of articulate sounds, absolute integrity of the mouth, teeth, lips, tongue, and palate is required. We are all acquainted with the modifi- cations in articulation, in persons in whom the nasal cavities resound unnaturally, from imperfection of the palate ; and the slight peculiarities observed after loss of the teeth and in hare-lip are sufficiently familiar. The tongue is gen- erally regarded, also, as an important organ of speech, and this is the fact in the great majority of cases ; but instances are on record in which distinct articulation has been pre- served after complete destruction of this organ.8 These cases, however, are unusual, and do not invalidate the great importance of the tongue in ordinary speech. It is thus seen that speech consists essentially in a modi- fication of the vocal sounds by the accessory organs, or parts situated above the larynx ; the latter being the true vocal in- strument. "While the peculiarities of pronunciation in differ- ent persons and the difficulty of acquiring foreign languages after the habits of speech have been formed show that the 1 WORCESTER, Dictionary of the English Language, Boston, 1864, p. xvii. 2 Numerous instances of preservation, more or less complete, of the faculty of speech after loss of the tongue, are quoted in works on physiology, among the most remarkable of which are those referred to by Dr. Elliotson (Human Physiology, London, 1840, p. 507). 516 VOICE AND SPEECH. organs of articulation must perform their function with great accuracy, their movements are simple, and vary with the peculiarities of different languages. The most interesting question, in its general physiological relations, is that to which the greatest part of this chapter has been devoted ; and that is the mechanism of the production of the voice. INDEX. Addison's disease, 354 Adipose tissue, anatomy of, 387 Albumen, diminution of, in the blood in the liver, 329 in milk, 95 Amyloid matter, in the liver,. . . . 320 Arytenoid muscle, 494, 495 Barreswil's test for sugar, 302 Barytone voice, X 504 Bas= voice, 504 Bellini, tubes of, 148 Bertin, columns of, 145 Bile, mechanism of the secretion and discharge of, 250 secretion of, from venous or arterial blood, 253 quantity of, 255 variations in the flow of, ... 256 influence of the nervous sys- tem upon the secretion of 257 mechanism of the discharge of, 257 general properties of, 258 specific gravity of, 259 reaction of, 259 coloration of the tissues by, . 259 composition of, 260 proportion of solid constitu- ents in, 261 inorganic constituents of,. . . 262 fatty and saponaceous con- stituents of, 262 lecithene of, 262 choline of, 262 peculiar salts of, 262 taurocholate of soda of, 263 process for the extraction of the biliary salts, 264 glycocholate of soda of, 266 Bile, origin of the peculiar salts of, 266 the biliary salts do not accu- mulate in the blood after extir- pation of the liver, 267 cholesterine of, 267 coloring matter of (biliver- dine),... 273 tests for, 274. Pettenkofer's test for, 275 excrementitious function of, 277 Bile-ducts, arrangement of, in the lobules of the liver, 241 Biliary passages (see liver), 245 Biliverdine, test for, 275 Bladder, mucous membrane of, 49, 181 anatomy of, 179 sphincter of, ^ 181 corpus trigonum, 181 blood-vessels, nerves, and lymphatics of, 182 influence of the nervous sys- tem on the movements of, ...".. 184 Blood-corpuscles, changes of, in passing through the liver, 329 Bones, physiological anatomy of, 479 fundamental substance of, . . 480 Haversian rods of, 481 Haversian canals of, 481 lacunae of, 481 canaliculi of, 482 marrow of, 483 generation of, by transplanta- tion of marrow, 485 periosteum of, 485 generation of, by transplanta- tion of periosteum, 486 Bone-corpuscles, 482 Bursae, 39, 42 Butter, 96 Buty rine, 96 518 INDEX. Canaliculi, of bone, 482 Capriline, in milk, 96 Caprine, in milk, 96 Caproine, in milk, 96 Carbonic acid, in the urine, 218 Cartilage, anatomy of, 486 Cartilage-cavities, 487 Cartilage-cells, 487 Cartilage, fibro-, 488 Caseine, 94 Cerumen, 69 Ceruminous glands, 60 Chest-register of the voice, 509 Chlorides, in the urine, 211 daily elimination of, in the urine, 212 Choleic acid, 265 Cholesterine, in the bile, 267 situations of, in the organism, 268 chemical properties of, 269 crystals of, 269 extraction of, from gall- stones, 271 extraction of, from the ani- mal tissues or fluids, 271 functions of, 277 origin of, in the economy,.. . 279 experiments showing forma- tion of, in the nervous tissue,. . 280 presence of, in the spleen, . . 280 experiments showing absence of, in the blood from paralyzed parts,.. ...'.• 284 elimination of, by the liver, . 286 experiments showing dimi- nution of, in the blood passing through the liver, 287 examination of the blood for, in simple icterus, cirrhosis, etc., 292 Cholesteraemia, 294 Cholic acid, 265 Choline, 262 Chordae vocales,. 492 Cilia, where found, 439 Ciliary glands, 63 motion, 438 Colostrum,. 102 corpuscles of, 103 composition of, 104 quantity of, as an indication of the probable quantity of milk, . 105 Connective tissue, ....." 454 Connective-tissue cells, 455 Consonants, 514 Contralto voice, 504 Corium (see skin), 114 Cream, separation of, from milk, . 89 • specific gravity of, 89 Creatine and c'reatinine, 204 daily elimination of, 207 Crico-arytenoid muscles, lateral,. . 494, 496 posterior, 495 Crico-thyroid muscles, 494, 495 Cytoblastions, in the skin, 115 Derma (see skin), 114 Diabetes, artificial, 173, 325 production of, by the in- halation of anaesthetics and irri- tating vapors, 327 Diphthongs, 514 Disassimilation, enumeration of products of, 391 Ear, fluid of labyrinth of, 46 ceruminous glands of,, 60 sebaceous glands of, 61 cerumen, 69 Elastic tissue, 442 Embryo-plastic elements, 455 Epidermis, 116 layers of, 116 Malpighian, or mucous layer of,.. 116 horny layer of, 116 desquamation and formation of cells of, 117 appendages of (nails and hair) 117 Epiglottis, action of, in phonation, 507 Epithelium, glandular, 18 pavement, 47 columnar, conoidal, or pris- moidal, 49 ciliated, situations of, 48 Excretion, general considerations of, 108 vicarious action in, 26 Excretions, distinction from secre- tions, 16, 108 enumeration of, 391 mechanism of the production of, 25 Eye, aqueous humor of, 46 Meibomian glands of, 62 Meibomian secretion, 70 Falsetto register of the voice, 509, 510 Fat, alleged production of, by the liver, 328 office of, in nutrition, 380 ESTDEX. 519 Fat, formation and deposition of, . 382 influence of food upon the deposition of, 384 condition of existence of, in the organism, 386 physiological anatomy of,. . . 387 Fatty degeneration (substitution), 382 Fehfing's test for sugar, 301 Ferrein, pyramids of, 146, 148 Fibrin, destruction of, in the liver, 329 | Fibro-cartilage, 488 Fibro-plastic elements, 455 Fibrous tissue, elastic, 442 inelastic , 454 Foetus, composition of the urine of, 221 formation of sugar in, 322 Gall-bladder, 248 Genito-spinal centre, 185 Germinal matter, 369 Glands, epithelium of, 18 condition of circulation in, during functional activity, 21 elimination of foreign sub- stances by, 27 motor nerves of, 31 effects of destruction of the nerves upon, 33 follieular, 35 tubular, 35 racemose (simple and com- pound), 35 ductless, or blood-glands, 36, 331 Glandular organs, classification of, 35 Glisson, capsule of, in the liver,.. 234 Glottis, appearance of, during or- dinary respiration, 498 • movements of, during pho- nation, 499 Glycine, 266 Glycocholate of soda, 266 Glycocholic acid, 266 Glycocoll, 266 Glycogenesis (see liver), 295 Glycogenic matter, 317 Hairs, situations of, 121 varieties of, 121 courses of, 121 length of, 122 number of, on the head,. . . . 122 elasticity and tenacity of,. . . 122 hygrometric and electric properties of, 123 Hairs, roots of, 123 follicles of, 123 summary of anatomy of the hair-follicles, 125 structure of, 126 growth of, 127 sudden blanching of, 127 Haversian rods and canals of bone, ' 481 Head-register of the voice,. . 509, 511 Heart, variations in the tempera- ture in the two sides of, 401 Heat, animal, 394 limits of normal variation of, 395 variations of, with external temperature, 396 variations of, hi different parts of the body, 398 variations of, in the two sides of the heart, 401 yariations of, at different pe- riods of life, 404 diurnal variations of, 406 influence of inanition upon, . 408 influence of diet upon, 409 influence of alcohol upon,. . . 410 influence of respiration upon, 411 influence of exercise upon,.. 412 development of, observed in a detached muscle, artificially excited to contraction, 414 influence of mental exertion upon, 415 influence of the nervous sys- tem upon, 415 variations in, due to reflex action, 416 influence of paralysis upon,. 417 sources of, 418 seat of the production of,. . . 420 relations of, to nutrition,... 422 relations of, to the consump- tion of nitrogenized matter and the production of nitrogenized excrementitious principles,.... 423 relations of, to the consump- tion of non-nitrogenized mat- ter, 424 relations of, to respiration,.. 426 consumption of oxygen and production of carbonic acid, in connection with the evolution of, 427 influence of the sympathetic system of nerves upon, 430 520 INDEX. Heat, increase of, in inflamed parts, 430 animal, intimate nature of the processes involved in the production of, 432 equalization of, 432 effects of clothing in the equalization of, 433 influence of cutaneous exha- lation upon, 433 Henle, tubes of, in the kidney,.. . 154 Hepatic artery (see liver), 236 secretion of bile after oblit- eration of, 253 Hepatic duct (see liver), 4 236 Hepatic veins (see liver), 238 Hippurates, in the urine, 202 in the blood, 203 Inelastic tissue, 454 Inorganic matters, office of, in nu- trition, 3*71 Inosates, in the urine, 204 Irritability of tissues, 462 Kidneys, effects of removal of,. 25, 163 differences in the color of the blood in the renal artery and vein, 26 effects of destruction of the nerves of, 33, 174 mucous membrane of the pelvis of, 49 physiological anatomy of, . . 144 weight of, 145 adipose capsule of, 145 pelvis of, 145, 178 : calices of, 145, 178 infundibula of, 145 cortical substance of, . 145, 149 columns of Bertin, 145 pyramids of ( Malpighi, Fer- rein), 146 • secreting and excreting por- tion of, 147 tubes of pyramidal substance of (tubes of Bellini), 148 Malpighian bodies of, 152 tubes of the cortical sub- stance of, 153 narrow tubes of Henle, 154 intermediate tubes in the cortical substance of, 155 blood-vessels of,. 1 56 blood-vessels in the Malpig- hian bodies, 157 Kidneys, stars of Verheyen, 159 lymphatics and nerves of,. . 159 summary of the anatomy of, 160 effects of extirpation of one kidney, 179 change in appetite and dis- position of animals after remov- al of one kidney, 170, 348 non-enlargement of the re- maining kidney after removal of one, 170 separation of foreign matters from the blood by, 175 — — alternation in the action of, 176 changes in the composition of the blood in, 176 absence of fibrin in the blood of the renal veins, 177 red color of the blood of the renal veins, 177 Lactates in the urine, 204 Lactation (see milk), 72 unusual cases of, 74 condition of mammary glands during the intervals of, 75 structure of the mammary glands in activity, 76 Lactose, 97 Lacunae of bone, 481 Language, 490, 513 Larynx, muscles of, 493 arytenoid muscle of, ... 494, 495 crico-thyroid muscles of, 494, 495 lateral crico-arytenoid mus- cles of, 494, 496 posterior crico-arytenoid mus- cles of, 495 thyro-arytenoid muscles of, 494, 496 Lecithene, 262 Lienine, 341 Life, definition of, 369 Liver, physiological anatomy of,.. 232 weight of, 233 ligaments and coverings of,. 233 lobules, or acini of, 234 capsule of Glisson, 234 blood-vessels of, 235 vaginal plexus of, 235 interlobular vessels of, 236 lobular vessels of, 237 intralobular veins of, 239 structure of a lobule of,. . . . 240 IXDEX. 521 Liver, arrangement of the bile- ducts in the lobules of, 241 excretory biliary passages,.. 245 racemose glands in, 247 vasa aberrantia of, 247 gall-bladder, hepatic, cystic, and common ducts of, 248 nerves and lymphatics of,. . 249 excretory function of, 277 elimination of cholesterine by,. 286 examinations of blood going to and from the liver, for choles- terine, 287 production of sugar by, 295 evidences of the glycogenic function of, " 296 discovery of the glycogenic function of, 298 examination of the blood of the portal system for sugar,. . . 803 examination of the blood of the hepatic veins for sugar, 305 experiments showing the ab- sence of sugar in, during life, . . 309 mechanism of the formation of sugar by, 316 glycogenic matter in, 317 extraction of glycogenic mat- ter from, 317 variations in the glycogenic function of, 321 non-formation of sugar by, in the early months of foetal life, 322 influence of digestion and of different kinds of food upon the glycogenic function of, 322 effects of the deprivation of food upon the glycogenic func- tion of, 1 324 influence of the nervous sys- tem upon the glycogenic func- tion of, 324 supposed action of, in the production of fat, 328 changes in the albuminoid and corpuscular elements of the blood of, 329 Liver-cells, 240 Liver-sugar, characteristics of,... 315 Locomotion, passive organs of,.. . 479 Malpighi, pyramids of, 146 corpuscles of, in the kidney,. . 1 52 blood-vessels in the corpus- cles of, in the kidney, 157 Malpighi, capsule of, in the spleen, 334, 335 corpuscles of, hi the spleen,. 335 Mammary glands, 72 — «- number and position of,. ... 73 condition of, during the inter- vals of lactation, 75, 80 structure of, during lactation, 76 nipple and areola of, 76 lactiferous or galactophorous ducts of, 77, 78 areolar muscle of, 77 lobes and lobules of, 78 acini of, 79 secreting vesicles of, 79 epithelium of the secreting vesicles of, 79 Margarine in milk, 96 Marrow of the bones, 483 generation of bony tissue from, by transplantation, 485 Medulloce'lls,. 483 Meibomian glands, 62 secretion, 70 Mezzo-soprano voice, 504 Middle register of the female voice, 509 Milk, mechanism of the secretion of 80 disappearance of epithelium during the secretion of, 82 proper diet during lactation, 83 influence of liquid ingesta upon the secretion of, 84 influence of alcohol upon the secretion of, 84 elimination of foreign sub- stances in, 85 influence of mental emotions upon the secretion of, 85 influence of the nervous sys- tem upon the secretion of, 86 quantity of, 86 general properties of, 88 specific gravity of, 88 reaction of, 88 coagulation of, 89, 95 separation of the cream from, 89 microscopical characters of, 89 composition of, 93 nitrogenized constituents of, 94 albumen of, 95 non-nitrogenized constituents of, 96 sugar of, 97 inorganic constituents of, ... 97 522 INDEX. Milk, gases of, 98 variations in the composition of, 98 composition of, at different periods of lactation, t 99 influence of menstruation and pregnancy upon the com- position of, 100 comparative composition of, in fair and dark women, and in different races, 100 influence of the quantity se- creted upon the composition of, 102 — : — secretion of, in the newly- born, 106 Milk-globules, 90 Movements, general considerations of, 436 of amorphous contractile sub- stance, 437 of cilia, 438 due to elasticity, 442 muscular, 445 Mucous membranes, anatomical di- vision of, 46 general anatomy of, 47 follicular and racemose glands of, 48 of the bladder, ureters, and pelvis of the kidney, 49 action of, in resisting the ab- sorption of venoms, 57 Mucus, mechanism of the secre- tion of, 49 general properties of, 51 microscopical characters of, 52 composition of, 52 nasal, composition of, 53 bronchial and pulmonary, composition of, 54 secreted by the mucous mem- brane of the alimentary canal, . 54 from the urinary passages, 55, 217 from the generative passages, 55 conjunctival, 56 general function of, 56 in the urine, 217 Muscles, involuntary, anatomy of, 446 action of, 448 voluntary, anatomy of, 449 « primitive fasciculi of, 450 sarcolemma of, 451 fibrillse of, 451 sarcous elements of, 452 fibrous and adipose tissue in, 453 perimysium of, 454 Muscles, connective tissue of, .... 45-i blood-vessels and lymphatics of, 456 connection of, with the ten- dons, 457 chemical composition of,. . . 457 physiological properties of, . 458 elasticity of, 459 tonicity of, 460 sensibility of, 460 contractility, or irritability of, 461 persistence of contractility in, after death, 462 distinction between muscular and nervous irritability, 463 influence of woorara upon the irritability of the nerves of, 464 influence of sulphocyanide of potassium upon the contrac- tility of, 465 influence of the nervous sys- tem upon the irritability of, ... 466 influence of the circulation upon the irritability of, 466 restoration of the contractil- ity of, by injection of blood, . . . 467 contraction of, 468 shortening and hardening of the fibres of, 469 no variation in the absolute volume of, during contraction, . 469 changes in the form of the fibres of, during contraction,. . . 470 contraction of, excited by electricity applied to the nerve, 470 single contraction of (spasm), 471 period of a single contrac- tion and relaxation of, 472 mechanism of prolonged con- traction of (tetanus), 474 sound produced by contrac- tion of, 475 fatigue of, 476 electric phenomena in, 476 Muscular effort, 477 Musculine, 458 Myeloplaxes, 484 Myolemma, 451 Myosine, 458 Nails, anatomy of, 118 connections of, with the epi- dermis, 120 growth of, 120 Nerves, motor nerves of the glands, 31 IXDEX. 523 Nervous system, influence of, upon secretion, 24, 28 exci to-secretory, 29 influence of, upon nutrition, . 388 Xeurine, synthesis of, 195 Xitrogen in the urine, 218 Xitrogenized principles, office of, in nutrition, 373 Xon-nitrcgenized principles, office of, in nutrition, 378 Xutrition, general considerations, 366 office of principles (inorgan- ic) that pass through the organ- ism, 371 office of principles consumed in the organism, 373 office of nitrogenized princi- ples in, 373 effects of systematic diet and exercise upon, 374 office of non-nitrogenized principles in, 378 influence of the nervous sys- tem upon, 388 influence of exercise upon, . 388 influence of age upon, 390 Oleine, in milk, 96 Oxalate of lime, in the urine, 208 Oxygen, in the urine, 218 Parotid gland, motor nerve of, ... 32 Pericardial secretion, 42 Perimysium, 454 Periosteum, 485 generation of bony tissue from, by transplantation, 486 Peritoneal secretion, 44 Perspiration (see sweat), 131 effects of covering the entire surface with an impermeable • coating, 132 Phonation (see voice), 490 movements of the glottis in,. 499 Phosphates in the urine, 213 derivation of, 214 influence of food upon the elimination of, 214 comparative proportion of, in the carnivora and the herbivora, 214 connection of elimination of, with disassimilation of the ner- vous tissue, 215, 231 variations in the elimination of, 216 Phosphates, daily elimination of, . 216 Picromel, 262 Pineal gland, 365 Pituitary body, 364 Pleural secretion, 44 Portal vein (see liver), 235 secretion of bile after oblit- eration of, 253 Protoplasm, 368, 437 Purpurine, ; 217 Sarcode, movements of, 437 Sarcolemma, 451 Sarcous elements, 452 Sebaceous fluids, varieties of, .... 57 Sebaceous glands, structure of,. . . 58 connection of, with the hair- follicles, 58 Sebaceous matter, 63 microscopical appearances of, 64 composition of, 65 Sebum, 63 Secreting organs, general struc- ture of, 33 classification of, 35 Secreting membranes, 35 Secretion, condition of the circula- tion in, 20 intermittent character of,. . . 22 action of the nerves in,.. . 24, 28 influence of the composition of the blood upon, 27 influence of blood-pressure upon, 27 modifications of the influence of pressure, through the nerves, 28 excito-secretory system of nerves, 29 reflex action in, 32 influence of pain, mental emotions, etc., upon, 33 distinction from transuda- tion, 34 Secretions, general considera- tions, 13 relations of, to nutrition,. . . 14 definition of, 14 division of, 15 distinction from excretions,. 16 fluids produced by simple transudation, sometimes called secretions, 17 mechanism of the production of, 18, 22, 23 action of epithelium in the production of, 18 524 INDEX. Secretions, formation of charac- teristic elements of, 19 elimination of foreign sub- stances in, 27 classification of, 37 Semivowels, 514 Serous membranes, 39 structure of, 40 Serous secretions, 43, 44 Silicic acid, in the urine,. 216 Skin, general function of, 110 general appearance of,. .... Ill extent and thickness of,.. . . 112 layers of, 113 muscles of, 113 true skin, or corium, 114 contraction of non-striated muscles in the substance of, . . . 114 reticulated layer of, 114 papillary layer of, 115 epidermis of (see epider- mis), 116 effects of covering the entire surface with an impermeable coating, 132 amount of exhalation from, 139, 433 discoloration of, accompany- ing disorganization of the supra- renal capsules, 354 Smegma preputiale,. 66 of labia minora, 66 Soprano voice, 504 Speech, mechanism of, 513 action of the tongue in, .... 515 Spleen, anatomy of, 332 capsule of Malpighi, 334 fibrous structure of (trabecu- IBB), 335 Malpighian corpuscles of, ... 335 blood - corpuscle - containing cells of, 338 vessels and nerves of, 339 • chemical constitution of, ... 341 functions of, 341 increase of the white corpus- cles of the blood in, 342 diminution of the red corpus- cles of the blood in, 343 variations in the volume of, during life, 343 extirpation of, 345 action of, as a diverticulum for the blood, 344 voracity in animals after ex- tirpation of, 346 Spleen, ferocity in animals after extirpation of, 347 Spleen-pulp, 337 Stercorine in the faeces, 291 Submaxillary gland, difference in the color of the blood in the ar- tery and vein of, 20 motor nerve of, 31 Sudoric acid, 142 Sudoriparous glands, anatomy of, 134 length of coil of, 137 Sugar, production of, in the liver, 295 process for the determina- tion of, in the liver and blood, . 300 Fehling's test for, 301 BarreswiPs test for, 302 examination of the blood of the portal system for, 303 examination of the blood of the hepatic veins for, 305 — : — examination of the blood from the right heart for, 306 characteristics of sugar pro- duced by the liver, 315 mechanism of the production of, in the liver, 316 effects of the inhalation of anaesthetics and irritating va- pors on the production of, 327 destination of, in the econ- omy, 328 office of, in nutrition, 379 Sugar of milk, 97 Sulphates, in the urine, 213 Sulphocyanide of potassium, in- fluence of, upon the muscles, . . 465 Suprarenal capsules, 349 structure of, 360 vessels and nerves of, 353 chemical reactions of, 353 functions of, 354 discoloration of the skin ac- companying disorganization of, 354 extirpation of, 356 Sweat, mechanism of the secre- tion of, 137 influence of the nervous sys- tem on the secretion of, 138 quantity of, 139 general properties of, 140 composition of, 141 peculiarities of, in certain parts, 142 urea in, 142 Sympexions, 360, 365 Synovial membranes, 40 INDEX. 525 Synovial fringes, 42 Synovial fluid, 44 — — composition of, 45 Taurine, 265 Taurocholate of soda, 263 Taurocholic acid, 265 Tendons, connection of, with mus- cles 457 Tenor voice, 504 Thymus gland, 361 Thyro-arytenoid muscles, 494, 496 Thyroid gland, 359 structure of, 360 functions of, 361 Tongue, action of, in phonation, . . 508 action of, in speech, 515 Trachea, action of, in phona- tion, 507 Training, 374 Transudation, distinction from se- cretion, 34 Trigone, 181 Tiiphthongs, 514 Tunica vaginalis, secretion of,... 44 Unites, formation of, 202 Urea, accumulation of, in the cir- culation, after removal of the kidneys, 25, 163 proportion of, in the renal artery and renal vein, 164 presence of, in the lymph and chyle, 164 presence of, in the blood, after tying both ureters, 167 situations of, in the economy, 194 chemical formula of, 195 synthesis of, 195 change of, into carbonate of ammonia, 195 crystals of, 196 origin of, 196 alleged formation of, from other excrementitious matters, 199 daily elimination of, 200 influence of muscular exer- cise upon the elimination of, . . . 226 Ureters, mucous membrane of, 49, 178 anatomy of, 178 movements of, on the appli- cation of galvanism, 182 Urethra, 182 Uric acid, compounds of, in the urine, . . ... 200 Uric acid, daily elimination of, ... 202 Urina potus, urina cibi, and urina sanguinis, 224 Urinary passages, anatomy of,. . . 178 Urine, mechanism of the formation of, 162 influence of Ksntal emotions on the secretion of, 172 influence of blood-pressure on the secretion of, . .' 172 influence of special nerves on the secretion of, 173 effects of irritation of the floor of the fourth ventricle up- on the secretion of, 173 arrest of the secretion of, by division of the spinal cord,. . . . 173 effects of division of all the nerves of the kidney on the se- cretion of, 174 passage of foreign matters from the blood, 175 constant formation of, .... 175 alternation in the secretion of, on the two sides, 176 mechanism of the discharge of, 182 general properties of, 187 temperature of, 188 quantity of, 188 specific gravity of, 189 reaction of, 189 cause of acidity of, 191 composition of, 191 urea of (see urea), 194 urates of, 200 hippurates of, 202 lactates of, 204 inosates of, 204 creatine and creatinine of, . . 204 oxalate of lime of, 208 xantbine of, 209 fatty matter of, 210 inorganic constituents of,.. 210 chlorides of, 211 sulphates of, 213 phosphates of, 213 silicic acid of, 216 coloring matter and mucus of, 217 gases of, 218 variations in the composition of, 219 variations of, with age and sex, 220 composition of, in the foetus, 221 526 EST)EX. Urine, variations of, at different seasons, and at different periods of the day, 222 variations of, with food, 223 influence of muscular exer- cise upon the composition of,. . 226 influence of mental exertion upon the composition of, 229 Urrosacine, urochrome, urohaema- tioe, uroxanthine, 217 Uvula, action of, in phonation, . . . 608 Velum palati, action of, in phona- tion, 508 Tenoms, non-absorption of, by mucous membranes, 67 Verheyen, stars of, 159 Vernix caseosa, 67 composition of, 67 microscopical characters of, . 68 function of, 68 Vocal chords, 492 appearance of, during phona- tion, 499 Vocal organs, physiological anato- my of, 491 Voice, 490 mechanism of the produc- tion of, 497 characters of, in childhood,. 502 range of, 503, 504 different kinds of, 504 action of the intrinsic mus- cles of the laryux in, 505 action of the accessory or- gans in, ." 507 action of the trachea in, . . . 507 action of the epiglottis in, . . 507 action of the velum palati in, 508 action of the uvula in, 508 action of the tongue in,. ... 508 mechanism of the different registers of, 509 Vowels, 514 Woorara, influence of, upon the motor nerves, 464 Xanthine, in the urine, 209 2>. APPZWrON A CO.'S PUBLICATIONS. THE PHYSIOLOGY AND PATHOLOGY OF THE MIND. By HEI^-RY MIATJDSLEY, ]MI. r>., London. 1 volume, 8vo. Cloth. Price, 84,00. CONTEXTS : Part I.— The Physiology of the Mind. CHAPTER 1. On the Method of the Study of the Mind. u 2. The Mind and the Nervous System. " 3. The Spinal Cord, or Tertiary Nervous Centres ; or, Nervous Centres of Reflex Action. " 4. Secondary Nervous Centres ; or Sensory Ganglia ; Sensorinm Commune. " 5. Hemispherical Ganglia; Cortical Cells of the Cerebral Hemispheres: Ideational Nervons Centres ; Primary Nervous Centres ; Intellectorinm Commune. " 6. The Emotions. ". 7. Tolition. " 8. Motor Nervous Centres, or Motorium Commune and Actuation or Effectlon. u 9. Memory and Imagination. Part II.— The Pathology of the Mind. CHAPTER 1. On the Causes of Insanity. " 2. On the Insanity of Early Life. " 3. On the Varieties of Insanity. CHAPTER 4. On the Pathology of Insanity. - 5. On the Diagnosis of Insanity. " 6. On the Prognosis of Insanity. CHAPTER 7. On the Treatment of Insanity. " The first part of this work may be considered as embodying the most advanced expression of the new school in physiological psychology, which has arisen in Europe, and of which Bain, Spencer, Leycoch, and Carpenter, are the more eminent English representatives." — Home Journal. " The author has professionally studied all the varieties of insanity, and the seven chapters he devotes to the subject are invaluable to the physician, and full of important suggestions to the metaphysician." — Boston Transcript. " In the recital of the causes of insanity, as found in peculiarities of civilization, of religion, of age, sex, condition, and particularly in the engrossing pursuit of wealth, this calm, scientific work has the solemnity of a hundred sermons ; and after going down into this exploration of the mysteries of our being, we shall come up into active life again chastened, thoughtful, and feeling, perhaps, as we never felt before, how fearfully and wonderfully we are made." — Evening Gazette. "A BOOK WHICH 18 AS READABLE AS A NOVEL: HISTORY OF EUROPEAN MORALS, FROM AUGUSTUS TO CHARLEMAGNE. By W. E. H. LECKY, M. A. 2 vols., 8vo. 5OO pages each.. Price, ^G.OO. The Utilitarian School — Objections to the School — Consequence of acting on Utilitarian Principles — Utilitarian Sanctions — Intuitive School — Alleged Diversi- ties of Moral Judgment — Each of the Two Schools of Morals related to the Gen- eral Condition of Society — The Order in which Moral Feelings are developed. THE PAGAN EMPIRE. Stoicism — Growth of a Gentler and more Cosmopolitan Spirit in Rome — Rise of Eclectic Moralists — The People still very Corrupt — Causes of the Corruption — Effects of Stoicism on the Corruption of Society — Passion for Oriental Reli- gions— Neoplatonism. THE CONVERSION OF ROME. Examination of the Theory which ascribes part of the Teaching of the Hated Pagan Moralists to Christian Influence — Theory which attributes the Conversion of the Empire to the Evidence of Miracles — The Persecution the Church under- went not of a Nature to crush it — History of the Persecutions. FROM CONSTANTINE TO CHARLEMAGNE First Consequence of Christianity, a New Sense of the Sanctity of Human Life — The Second Consequence of Christianity, to teach Universal Brotherhood — Two Qualifications of our Admiration of the Charity of the Church — The Growth of Asceticism — The Saints of the Desert — Decline of the Civic Virtues — General Moral Condition of the Byzantine Empire — Distinctive Excellences of the Ascetic Period — Monachism — Relation of Monachism to the Intellectual Virtues — The Monasteries the Receptacles of Learning — Moral Condition of "Western Europe — Growth of a Military and Aristocratic Spirit — Consecration of Secular Rank. THE POSITION OF WOMEN. The Courtesans — Roman Public Opinion much purer — Christian Influence — Relation of Christianity to the Female Virtues. D. APPLETON & CO., Publishers, 9O, 92 & 94 Grand St., New York. Sent free by mail to any address in the United States, on receipt of the price. 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