Digitized by tine Internet Arciiive in 2008 witii funding from IVIicrosoft Corporation http://www.arcliive.org/details/animalcliemistryw01simouoft THE SYDENHAM SOCIETY INSTITUTED MDCCCXLIII LONDON M DCCCXLV. ANIMAL CHEMISTRY WITH REFERENCE TO THE PHYSIOLOGY AND PATHOLOGY OF MAN DR. J. FRANZ SIMON TRANSLATED AND EDITED BY GEORGE E. DAY, M.A. & L.M. Cantab. LICENTIATE OF TUE KOYAL COLLEGE OF PHYSICIANS. IN TWO VOLUMES VOL. I. LONDON PRINTED FOR THE SYDENHAM SOCIETY MDCCCXLV. OP \ 1 ^ (I IMIINTED BY C. AND J. ADLARD, BAKTIIOI.OMKU CLOSE. C EDITOR'S PREFACE. I HAVE much pleasure in presenting to the members of the Sydenham Society a translation of Simon's ' Chemistry of INIan/^ a work that obtained for its author a European repu- tation, and is universally regarded as by far the most complete treatise that has yet appeared on Physiological Chemistry. Until I became acquainted with this work in 1843, I enter- tained the idea of publishing a text-book of medical chemistry with the view of attempting to supply a deficiency in the medical literature of this country, which, I doubt not, has been felt by many of my brethren as much as by myself. But a careful perusal of the ' Chemistry of Man' convinced me that I should be doing better service to the profession by undertaking a translation of that work than by the publication of a separate treatise. Impressed with this feeling I wrote to the author, who immediately offered me all the assistance in his power, and promised me a considerable amount of original matter. I regret to say that his early and unexpected death in the autumn of the same year rendered this promise of comparatively Httle value. I have, however, freely availed myself of the permission granted me by the Council of the Sydenham Society to insert such additions as the progress of chemistry, since the original ' Physiologische und pathologische Anthropochemie mit Beriicksichtigung der eigentlichen Zoochemie. Berlin, 1842. b vi EDITOR'S PREFACE. publication of the work, has rendered necessary. These inter- polations, with the exception of one class, are distinguished by being included in brackets. I refer to the chemical essays of Simon, written with the view of filling up occasional deficiencies in his ' Chemistry of Man,^ and published in his ' Beitrage zur physiologischen und pathologischen Chemie und Mikroskopie/ This exception was made at the request of Dr. Simon, and its expediency and fairness is unquestionable. The ' Chemistry of Man' was preceded by a volume entitled ^ Chemistry of the Proximate Constituents of the Animal Body,' Avhich, being in fact a distinct work, (containing upwards of 500 closely printed pages,) it has been deemed unadvisable to translate in its original form. A brief Introduction,^ in a great measure based upon it, has been drawn up by myself, with the view of facilitating the perusal of the work to those who have not paid much attention to the recent progress of organic chemistry ; and liaving written it with this object, I have intentionally excluded many topics which some of my readers may consider should have found a place there. The following sketch of the life and writings of the Author, brief though it be, cannot be read without interest. It affords a striking illustration of the results that combined energy and talent are capable of evolving. Eranz Simon was the son of a sui'geon residing at Frankfort on the Oder, and was born on the 25th of August, 1807. He distinguished himself at a very early age as a skilful apothecary ; and, in volume 32 of ' Brande's Archiv,' we find his essay on the preparation and properties of tinctures, to which one of the Hagen-Buchholz prizes Avas awarded in 1829. Even in this essay we can trace the germs of some of his future speculations in physiological chemistry. The following year he ' In the compilation of the Introduction 1 ain likewise much indebted to Lehmann's ' Manual of Physiological Chemistry ;' and to Mulder's ' Chemistry of Vegetable and Animal Physiology.' EDITOR'S PREFACE. vii obtained the first prize (the gold medal) for his essay ou the l)est method of preparing infusions and decoctions (Brande's Archiv, vol. 35), a treatise equally remarkable for the extreme accuracy and care with which his experiments were conducted, and for the judgment displayed in his conclusions. In the year 1832 Simon came from the Rhine, where he had been practising as apothecary in different towns (Cleve, Diisseldorf, Coin, and Deutz,) to Berlin, where he passed his examination as apothecary with the highest credit, and where, in addition to the practical department of his profession, he attended lectures on chemistry and pharmacy. He now published a small pamphlet entitled ^A brief Examination of Professor Kranichfeld's Treatise on the necessity of a Fundamental Knowledge of Pharmacy in relation to sound Medical Practice,' one of the most argumentative, and -powerful replies that Kranichfeld's absurd and unfounded accusation against the German apothecary system elicited. From this period till the year 1838 he devoted himself to study, having, with this view, given up his public pharmaceutical avocations in the year 1835. He attended, for six terms, lectures at the High School of Berlin, on natural history, physics, mathematics, history, and philosophy; lie likewise published, conjointly with Dr. Meklenburg, a tabular view of chemistry (Berlin, Hirschwald.) Most of his leisure time at this period was devoted to toxicology, a subject on which he and his friend Dr. Sobernheim published a treatise which is regarded throughout Germany as the standard work on everything connected with poisons and poisoning. Some of the most important original investigations on which this work was based were originally published in Poggendorff's Annalen, vol. 40, On the 3d of October, 1838, Simon received the degree of Doctor of Philosophy for his celebrated thesis ' De Lactis Muliebris ratione chemica et physiologica/ which, in the course of the same year, was published, with considerable additions, in viii EDITOR'S PREFACE. the German language (Die Frauenmilcli, u. s. w. Berlin, Forstner, 1838), and fully established his reputation as one of the most successful investigators of the age in the departments of organic chemistry and microscopy. It was regarded by Berzelius and others of our first chemists as the most perfect work on the subject of which it treats. In 1839 his tabular ' View of the Mineral Springs of Europe, arranged with especial regard to their chemical composition and their physical and chemical characters^ (Die Heilquellen Europas, u. s. w., Berlin, Eorstner,) made its appearance, a work of very considerable labour, in which he collected and systema- tically arranged no less than 1045 analyses of European mineral waters; and in 1841 we find him an extensive contributor to Dr. Nicolai's ' Manual of Medical Jurisprudence,^ having, in fact, executed the whole of the chemical and toxicological portion of the work. About this time the first part of the ' Chemistry of Man' appeared; it was not, however, completed till the summer of 1842, in consequence of Simon's determination to render the work as rich as possible in original analytical obser- vations. With this view he was a constant attendant at Schonlein's clinical class, where his chemical services were highly valued, as manifested by the frequent reference made to them by that distinguished physician in his published Clini- cal Lectures. Scarcely had Simon concluded the ' Chemistry of Man' before he entertained the idea of editing a quarterly periodical devoted to his favorite pursuits, physiological and pathological chemistry. It appeared under the title of ' Beitrage zur physiologischen und pathologischen Chemie und Mikro- skopie, in ihrer Anwendung auf die praktische Medizin.' He lived to edit only three numbers. The fourth (edited by his friend Dr. Minding) contained the melancholy tidings of his death, which took place at Vienna on the 23d of October 1843, after an illness of only four weeks. Though no longer amongst us, the good that he did died not with him ; his works, no EDITOR'S PREFACE. ix less than his example, have stimulated others to follow in his track, and to build upon the solid basis that he has left them. Even the very periodical that he commenced so shortly before his death is still conducted (under a different title) by an able chemist, and is producing results worthy of its original founder. I gladly avail myself of this opportunity of expressing my obligations to the Council of the Sydenham Society for the promptitude with which they accepted my suggestion respecting the expediency of pubhshing an English edition of this work, and for intrusting me with the editorship of it ; to one of that body, Mr. Ancell, I am very deeply indebted for the kind and valuable assistance that he has afforded me in the preparation of this volume for the press. Amongst the many other friends to whom my acknowledgments are due, I must especially men- tion Dr. Allen Thomson, Dr. Percy, Dr. Wright, and Dr. Golding Bird. G. E. D. Soutkwick street, Hyde Park. AUTHOR^S PREFACE. The completion of the ' Chemistrv^ of Man^ lias been una- voidably delayed beyond the time at which it was advertised to aj)pear, in consequence of the large number of original ana- lyses that I found it requisite to institute. As, however, these analyses materially increase the value of the work, I trust that my apparent procrastination will be readily forgiven. The present volumes comprise physiological and pathological chemistr3^ They treat of the physical and chemical relations of the fluid and solid portions of the human body in a state of liealth, and of the modifications they experience in different dis- eases. Moreover, in every instance, the chemical examination of tlic fluids and solids of the lower animals is appended to each chapter. The order in which the various matters treated in these volumes are discussed must be regarded rather as natural than physiological. After the circulating fluids, viz., the blood, lymph, and chyle, with which I commence, — I treat of the secreted and excreted fluids, as, for instance, those of the chy- lopoietic system, of the female breast, of the mucous membranes and skin, of the kidneys, &c. : next in order, I take the fseces and vomited matters. I then consider the various tissues that enter into the composition of the animal body, as, for instance, the bones, muscles, skin, and glands ; and I conclude with a description of various solid and fluid morbid products, such AUTHOR'S PREFACE. xi as calculi, tubercular and carcinomatous matter, dropsical effusions, &c. I have made myself practically conversant Avitli tlie most approved methods of analysing the different fluids and solids described in this work ; and, as far as my resources permitted, I have endeavoured to determine the various physical and che- mical modifications they undergo in the course of different dis- eases. My attention has been especially directed to the study of those fluids that are of the greatest importance to the practical physician. Within the space of a few years I have made about 170 quantitative analyses of various animal matters, of which the very large majority refer to human blood, milk, and urine, and on which I lay the foundation for the patholo- gical chemistry of those fluids. In fact, without these analyses it would have been impossible to publish a work worthy of the name of ' The Chemistry of Man ;' for the essays of Andral and Gavarret on the Blood, and of Becquerel on the Urine, did not appear until I had made considerable progress in my work. I have deemed it, in every case, my duty to incorporate the results of other chemists with my own, and if, in any instance, I have failed in acknowledging the sources from which my statements have been drawn, the fault is one of inadvertence, not of design. All purely physiological matter, not bearing directly on chemistry, has been omitted ; but microscopic in- vestigation, especially in those instances in which it strengthens the evidence of experimental chemistry, has been deemed legi- timately deserving of a place in this treatise. My views regarding the metamorphosis of the blood, and its relation to nutrition and animal heat, were first communicated, at Erlangen in the autumn of 1840, to the medical and chemi- cal section of Associated Naturalists ; and my subsequent re- searches into the chemical constitution of the blood and urine confirm my belief in their general accuracy. These views may be summed up in the following terms : The blood is subjected xii AUTHOR'S PREFACE. to a continuous metamorphosis, which may be regarded as the expression of its vitality. The nutrition of the peripheral sys- tem is effected by the liquor sanguinis^ not by the blood-cor- puscles. The liquor sanguinis affords nutriment to the cells and organs, which possess an inherent power of selecting proper material, or of forming it from non-homologous matter, at the same time secreting the products of decomposition. The prin- cipal nutritive matters in the liquor sanguinis are albumen, fibrin, and fat. The chief products of this metamorphosis are the extractive matters and lactic acid, which occur in the ex- cretions, especially in the urine. Urea, bilin, and carbonic acid are either not products of the metamorphosis of the blood during the act of nutrition in the peripheral system, or at most they are only in part formed by it. They must be regarded as pro- ducts of the vital energy of the blood-corpuscles, which, doubt- less, possess the same power of attracting nutriment, and of throwing off decomposed products, as other living cells. The proper nutriment of these corpuscles is oxygen, albumen, and probably also fat, which are furnished them by the liquor san- guinis. The most important products of their metamorphosis are carbonic acid, urea, fibrin, extractive matters, and very pro- bably some of the constituents of the bile. The leading and most important object of this \dtal energy of the blood-corpus- cles is the production of animal heat, without which every function of the organism, nay even life itself, would be instan- taneously annihilated. The production of animal heat is due to the combination of oxygen with the carbon of the globulin ;i the principal products of this reaction are carbonic acid and urea, or uric acid, (which is excreted as a substitute for urea in most of those classes of animals in which elliptic blood-corpus- ' [Simon's views respecting the production of animal heat approximate closely to those expressed by our countryman, Mr. Ancell, in his lltli lecture on the blood. Sec Lancet, 1840, vol. i. p. 829, or Dr. Posner's German edition of the col- lected lectures, p. 200.] AUTHOR'S PREFACE. xiil cles occur.) Tlie urea excreted may thus be regarded as a measure or equivalent of the animal heat developed. The production of blood-corpuscles and the formation of blood are intimately connected with nutrition : when the food is too scanty and insufficient, the amount of blood, and especially of blood-corpuscles, is diminished ; when the nutriment is proper and abundant, the reverse takes place. In the former case, there- fore, the vital energy is depressed, the secretions and excretions are diminished, and the animal heat sinks ; while in the latter case exactly the reverse is observed. In the normal state there is an equilibrium preserved between the production and con- sumption of blood-corpuscles. The food is prepared, and to a certain extent assimilated, before it enters the blood. The vital energy of the blood-corpuscles continues even during a perfect abstinence from food, and carbonic acid and urea continue to be formed, although their amount gradually diminishes in a direct ratio with the diminution of the blood-corpuscles. Moreover, the amount of carbonic acid and the formation of m'ea are lessened by a torpid, and increased by an excited cir- culation ; and in proportion to the amount of corpuscles and to the rapidity of the cu'culation, so much the higher is the animal temperature. Thus in birds we observe a high tem- perature, and the reverse in the amphibia. In chlorotic, and also in very aged persons we find a low temperature, and a diminished excretion of urea, while in inflammatory diseases, and after prolonged corporeal exertion the temperature rises, and there is either a relative or an absolute increase of urea; in the former case, even in the absence of all nitrogenous food. The capillary and cutaneous systems tend to regulate an ex- cessive rapidity of the circulation, and to prevent the animal heat from exceeding a certain limit. If we only knew whether, and in what manner, the pulmo- jiary exhalation is changed in various diseases, (especially in rela- tion to the amount of carbonic acid contained in it,) whether xiv AUTHOU'S PREFACE. the carbonic acid always increases relatively with the urea, or in certain cases with the uric acid, and if further, we possessed experiments illustrative of the effects of diseases, and of varied diet on the bile, we should then have a more solid basis than we now occupy, .on which to found our chemical inquiries, while the acquisition to the science of medicine would be po- sitive and incalculable. The questions here involved must, however, unfortunately, at the present time, be regarded as unanswerable. We cannot doubt that the pulmonary exhalation does vary, under different circumstances, in the amount of car- bonic acidj for instance, more carbonic acid is exhaled during prolonged corporeal exertion than when the body is in a state of repose ; although, as far as I am aware, no experiments on this subject have yet been instituted.' We have, however, con- clusive evidence that the amount of urea is increased under these circumstances. On the other hand, in the researches of Trommer regarding the passage of sugar into the portal blood of horses, this sub- stance could not be detected in the chyle nor in the arterial or venous blood, which renders it more than probable that the liver not only serves the purpose of modifying the composition of the blood, but likewise effects the object of altering or re- moving abnormal substances from it that have been absorbed by the mesenteric veins. Hence this organ appears, in a cer- tain degree, to take a share in the process of digestion, an opinion supported by Berzelius. Future investigations re- specting the functions of the liver may lead to very important results, and throw much light on many of the most obscure departments of physiology. Although very little has yet been done in physiological and pathological chemistry, the rational physician, who ventures to cast aside the trammels of dogmatism and empii'icism, cannot, ' [The experiments of Scharling on this siihject were made after the publication of the ' Chemistry of Man.' A brief notice of them is given in p. 129 of this volume.] AUTHOR'S PREFACE. xv for an instant, doubt tliat pathology, therapeutics, and diag- nosis, are only safely based on chemistry, physiology, and morbid anatomy: he cannot entertain a doubt that the same chemistr}' with which he scans the changes in crude inorganic matter, Avill likewise enable him, if not at present, yet surely at some futiu-e period, to detect the variations in the composition of the animal fluids and solids, some of which are dependent on phy- siological, others on pathological causes, and will throw a new light on the normal functions of the organism, as well as on the various processes of disease. After contemplating the dependence of \ital manifestations on the unceasing metamorphosis of the animal body, and the secretions and excretions as its products ; after glancing at the physical and chemical modifications that these secretions and excretions undergo in numerous pathological conditions, and observing how these changes affect the structure and chemical conditions of the different organs, we can no longer entertain a doubt that all morbid phenomena are accompanied by me- tamorphoses in the organism, different from those that occur in the normal condition. But it will require an immense number of analyses in order to ascertain and determine these modifi- cations, to express them in definite terms, to connect them duly with functional distiu'bances in the organism, or with other symptomatic phenomena; and, finally, as far as possible, to endeavour to discover their origin. In such researches the mere chemist can do little : in order to produce results really serviceable to science, physiology and pathology are as essential as chemistry itself, and no one can hope to advance this de- partment of scientific inquiry who does not include, in his own person, the chemist, the physiologist, and the pathologist. Every science is slowly and gradually developed. Physio- logical and pathological chemistry forms no exception to this rule : it is still a mere infant science, that has scarcely attained a self-dependent existence. The reader must therefore not xvi AUTHOR'S PREFACE. require of this work more than the present state of the science will enable me to present him with. He will find in it che- mical facts which the physiologist and pathologist may render of further service : the few scattered ideas concerning the me- tamorphosis of the blood, and the probable connexion between various diseases and certain modifications in the composition of the different animal fluids, may serve as connecting links for further investigations. The materials for my analyses have been chiefly derived from the Charite (hospital) of this city, from some of the public cliniques, from private practice, and from the royal veterinary school. I gladly avail myself of this opportunity of publicly expressing my thanks to Drs. Schonlein, Wolff", and Romberg, as well to Professors Gurlt and Hertwig, and the other pro- fessional friends who have favoured me with their advice and assistance. I must likewise express my obligation to Dr. V. Behr, who assisted me for a considerable time in my re- searches on the urine. That this work may succeed in encouraging a taste for a department of science, whose cultivation and further develop- ment is, at the present time, imperatively demanded by the medical public, is the most sincere wish of The Author. Berlin, /Ipril 1842. TABLE OF CONTENTS. INTRODUCTION. By Dr. Day, Page I. Mineral Constituents. Class 1. Constituents useful by their physical properties . • . 1 2. Constituents useful by their chemical properties . . 2 3. Incidental constituents . . . . .3 II. Organic Constituents. Class I. Nitrogenous constituents : 1. Protein ....... 5 2. Albumen 15 3. Fibrin 18 4. Casein 19 5. Pepsin .... 22 6. Ptyalin 24 7. Gelatin — chondrin and glutin 25 8. Pyin 29 9. Extractive matters 30 10. Colouring matters 39 a. Of the blood ib. b. Of the bile 43 c. Of the urine 45 11. Bilin . . ib. 12. Urea .... 49 13. Uric acid 53 1 4. Hippuric acid 61 15. Uric oxide 62 16. Cystin . 64 Class 11. Non-nitrogenous constituents : 1. Animal sugars . 65 a. Sugar of milk . ib. b. Diabetic sugar . 66 CONTENTS. Page 2. Saponifiable fats ..... . 69 a. Fatty bases . . . . • . 70 Glycerin ...... . ib. Oxide of cetyl ..... . ib. Cerain ...... . ib. b. Fatty acids ...... . 71 Margaryl and its oxides — stearic and margaric acids . ib. Oleic acid ..... . 74 Butyric and its allied acids . 75 Cerebric and oleophosphoric acids . 81 3. Non-saponifiable fats : a. Cholesterin ...... . 82 b. Serolin ...... . 83 4. Organic acids : a. Lactic acid ...... . 84 b. Oxalic acid ...... . 85 c. Acetic acid ...... . ib. CHEMISTRY OF MAN. CHAPTER I. On the proximate analysis of compound animal substances . 87 CHAPTER II. The circulating fluids — the blood The general physical relations of the blood. Microscopic analysis of the blood ..... The general chemical relations of the blood. The general chemical relations of the blood-corpuscles „ „ colouring matter of the blood ,, „ „ nuclei of the blood-corpuscles ,, „ „ plasma (liquor sanguinis) The retardation or prevention of coagulation Acceleralion of the 9oagulation ..... On the chemical physiology of the blood. On the formation of the blood ...... On the forces that circulate the blood ..... On tlie process of respiration ...... Absolute quantity of expired carbonic acid .... Relations of the constituents of the expired air to the theory of respiration Respiration of the foetus and of animals .... On the metamorphosis of the blood ..... 100 102 107 112 ib. 114 115 117 118 122 123 128 131 136 139 CONTENTS. On animal lieat ........ Metamorphosis of the blood in the nutrition of the organism Active metamorphosis of the blood ..... Special chemistry of the blood. Proximate constituents of the blood ..... On the methods of analysing the blood ..... Analysis of coagulated blood ...... On the healthy blood in relation to phyniology. On the distinctive characters of arterial and venous blood Properties of the blood of the vena portae ; its comparison with arterial blood Properties of the blood of the hepatic vein ; its comparison with the blood of the vena portse ........ Properties of the blood of the renal veins ; its comparison with the blood of the aorta ....... Comparison of venous blood with the blood of the capillaries Review of the modifications and changes that the blood undergoes in the corjse of the circulation ..... On the absolute composition of healthy venous blood On the differences of the blood dependent on sex . ,, ,, „ on constitution „ „ „ on temperament „ „ ,, on age ON DISEASED BLOOD. The pathological chemistry of the blood Ancb-al and Gavarret's method of analysis On the effect of repeated venesections on the First form of diseased blood : hyperinosis Blood in inflammatory affections general ,, metrophlebitis puerperalis „ phlegmasia alba dolens „ carditis „ bronchitis „ pneumonia „ pleuritis „ angina tonsillaris (amygdalitis) „ hepatitis and lienitis . ,, peritonitis „ nephritis and cystitis . „ rheumatismus acutus . „ erysipelas „ phthisis tuberculosa „ febris puerperalis „ eclampsia „ carcinoma meduUare colli uter blood y Page 142 147 152 166 167 190 192 201 208 213 217 218 227 234 236 ib. ib. 239 240 248 250 251 252 253 254 255 258 266 268 ib. 269 273 ib. 277 279 282 ib. 284 CONTENTS. Second form of diseased blood : hypinosis Blood in typhus abdoininalis „ febris continua „ variola and varioloid disease „ rubeola .... „ scarlatina .... „ febris intermittens „ liEemorrhagia cerebralis Third form of diseased blood : spancemia Blood in anaemia and hydrsemia „ carcinoma .... „ scrofulosis .... ,, chlorosis .... „ scorbutus .... „ morbus maculosus Werlhofii (land-scurvy) „ hemorrhages „ puqjura haemorrhagica „ typhus peteclualis putridus (yellow fever, plague) Fourth form of diseased blood : heterochymeusis 1. Blood containing urea ; urcemia Blood in morbus Brightii . „ cholera .... 2. Blood containing sugar : melitcemia Blood in diabetes 3. Blood containing bile-pigment : choleemia Blood in icterus 4. Blood containing fat : piarhcemia 5. Blood containing pus : pyohamia 6. Blood containing animalcules Page 286 288 295 298 300 ib. 301 302 306 308 309 ib. 310 315 316 317 319 ib. 321 ib. ib. 325 327 ib. 329 ib. 332 333 335 SUPPLEMENT TO THE BLOOD. Blood during pregnancy Menstrual blood Locliial discharge Blood of animals 335 337 338 339 The lymph The chyle 350 354 CHEMISTRY OF MAN. IXTRODUCTION. The proximate constituents of the animal body may be divided into two great classes^ the mineral and tbe organic ; eacb of wliicli admits of several sub-di\dsions. I. MINERAL CONSTITUENTS. The Mineral Constituents may be advantageously classed in three groups^ comprising, i, Those which are of ser^-ice in the animal body, in consequence of their physical properties ; ii, Those which effect important objects in the system by their chemical actions; and iii, Those which, being only incidentally present, may be eliminated without exerting any unfavorable effect on the economy. CLASS I. CONSTITUENTS USEFUL BY THEIR PHYSICAL PROPERTIES. 1. Water. This substance is so universally diffused, and its uses are so ob\ious as to render any observations unnecessary. 2. Phosphate of lime, in the importance of its physical proper- ties to the animal organism, undoubtedly ranks next to water. Phosphate of hme or, as it is often termed, bone-earth, consists of 8 eq. of Hme and 3 eq. of phosphoric acid; its empirical formula therefore is 8 Ca O + 3 PO ; but there can be no doubt that ] 2 MINERAL CONSTITUENTS. it is a compound of two tribasic phosphates of lime^ namely 2Ca O, HO, PO3 + 2 (3 Ca O, POJ. It consists of 51-55 parts of hme, and 48-45 of phosphoric acid. It occurs in bone, blood, milk, urine, faeces, &c. 3. Carbonate of lime forms the principal part of the skeleton in the invertebrata ; it also occurs in greater or less proportion in the bones of the higher animals and man, in the urine of the graminivora, and in certain morbid concretions. It contains 56*29 parts of lime and 43'71 of carbonic acid. 4. Phosphate of magnesia is very frequently associated with phosphate of lime. In a crystalline state its formula is HO, 2 Mg O, PO^ + 2 HO + 12 HO. (Graham in Phil. Trans. 1837.) It occurs in bone, blood, milk, shell of eggs, urine of man and carnivora, intestinal concretions, faeces, &c. After the removal of the water of crystallization it consists of 36-67 parts of mag- nesia, and 63*33 of phosphoric acid. Phosphate of magnesia and ammonia, or, as it is frequently termed, ammoniaco-magnesian phosphate, is a perfectly distinct salt. Like the former, it is a tribasic salt, of which the 3 atoms of base are, 1 atom of oxide of ammonium, and 2 atoms of magnesia, with 12 atoms of water of crystallization, 10 of Avliich may be expelled without any loss of ammonia. Its formula therefore is NH^ O, 2 Mg O, PO^ + 2 HO + 10 HO. Crystals of this salt have been observed in the excrements in typhus and other diseases ; it is also present in certain states of the lu'ine, and is a frequent constituent of urinary calculi. 5. Fluoride of calcium occurs in the animal organism in very minute quantity. It is much more abundant in fossil than in recent bones. CLASS II. CONSTITUENTS USEFUL BY THEIR CHEMICAL PROPERTIES. 1. Hydrochloric acid exists in the digestive fluid of man, of the mammalia generally, and of birds. It has been detected by Lehmann in morbid saliva. 2. Hydrofluoric acid has only been detected in the gastric se- cretion of birds. 3. Chloride of sodium exists in the blood, gastric juice, urine, bone, cartilage, &c. INCIDENTAL. 3 4. Carbonate of soda is a very common ingredient in the asli of animal substances ; in most cases it is derived from com- pounds of soda with organic acids, especially lactic acid. It is also found in the urine of the graminivora. 5. Phosphate of soda occurs in the blood, lymph, chyle, bile, milk, and imne. Its formula is HO, 2 Na 6, PO,, +24 HO. On the addition of muriate of ammonia to a solution of this salt, we obtain the " sal microcosmicus " of the older chemists, which is found in considerable quantity in decomposed animal fluids; its formula is HO, NH^ O, NaO, PO^ + S HO. The recent investigations of Enderlin tend to prove that the phos- phate of soda that most commonly occurs in the animal fluids and tissues, contains 3 atoms of soda, and may be represented by the formula 3 Na O, PO,. 6. Chloride of calcium is found in the gastric juice and saliva. 7. Chloride of iron (apparently the proto-salt) occurs in he gastric juice. 8. Iron is found in considerable quantity in hcematin, the prin- cipal colouring matter of the blood ; also in lymph, chyle, black pigment of the eye, hair, &c. In what state it exists, whether as a peroxide or protoxide, or either, is not known. It is also found in lesser proportion in bile, urine, sweat, milk, &c. In some of these fluids it is stated to exist as a phosphate. CLASS III. INCIDENTAL CONSTITUENTS. 1. Chloride of potassium is found in almost aU the animal fluids. 2. Alkaline sidphates occur in small quantity in most of the animal fluids, in the blood, milk, urine, and sweat. Mitscherlich could not detect any alkaline sulphates in the saliva, and Lehmann has recently shown that they do not exist in the bile, although they may be produced in the ash. 3. Carbonate of magnesia has been found in alvine concre- tions, minary calculi, &c., in man and the mammalia. It occurs in considerable quantity in the urine of the graminivora, and is a constituent of the shell of the egg. Berzelius suggests the probability of magnesia being contained in bone, not as a phosphate but as a carbonate, and that the phosphate of mag- nesia is produced during analysis. 4. Manganese has been found in the hair ; it has also been 4 MINERAL CONSTITUENTS. detected in liiiman gall-stones^ (in one instance there was found as much as 0'3|^' of the protoxide of manganese,) and traces of it have been observed in the mnnary calculi of the graminivora. 5. Silica has been found in small quantity in the enamel of the teeth, in bone, urine, minary, intestinal, and biliary calculi, hair, and saliva. It is found in considerable quantity in the excrements, the amount varying with the natui'e of the food. In the sheep the excrements have been observed to contain as much as 6-OjJ of silica. 6. Alumina. Traces of this substance were detected by Vauquelin, in human bones; it has been found in considerable quantity in fossil teeth and horns. The cu'cumstance of its being an occasional constituent of intestinal concretions coincides with Lehmann^s experiments, in which he found that when alumina was introduced into the system, it was carried off by the faeces. 7. Arsenic was recently stated by Orfila to be a normal consti- tuent of human bone. This opinion has, however, since been withdrawn, and there is little doubt that there was some fal- lacy in his experiments. 8. Copper is considered by Devergie, Lefortier, and Orfila, to be a normal constituent of all the soft parts, as well as of the blood of healthy persons. Devergie^ analysed the Aiscera of five persons and found it in eveiy instance. It has also been found in the sweat. 9. Lead has been found by these chemists in the same cases as copper. 10. Ammoniacal salts. In the blood, lymph, chyle, and milk, there are no appreciable ammoniacal salts. They have been observed in some cases in the sweat, and they occur in a small proportion in the urine. ' The notation 2 represents per rentage. ' These ol)servations have recently heen confirmed by M. Barse, who succeeded in finding both copper and lead in the bodies of two persons to whom they could not have been given for poisons. It seems from the analyses of Signor Cattanei that neither of these metals exists in the bodies of new-born children or infants ; and Rossignon has recently pointed out the soiu'ces from which the bodies of adults pro- bably derive their copper. He has found this metal in gelatin, chocolate, bread, coffee, sugar, &c. PROTEIN. 5 II. ORGANIC CONSTITUENTS. The Organic Constituents may be arranged in two principal groups, tlie former embracing tlie nitrogenous, the latter the non-nitrogenous matters. In the nitrogenous group we have protein, and its various modifications — gelatin, bilin, and the pro- ducts of its metamorphosis — luematin, urea, uric acid, &c. : in the non-nitrogenous we place the animal sugars, fats, lactic and acetic acids, &c. Src. CLASS I. XITROGEXOUS CONSTITUENTS. 1. Protein. Under this head we shall consider three very important com- pounds which are formed in the vegetable kingdom, and wdiich are also found to constitute the greater part of the animal body. These are Albumen, Fibrin, and Casein. Two most important discoveries have recently been made regarding these substances. The first is the discoveiy made by Mulder that albumen, fibrin, and casein are nothing more than modifications of one com- pouud to uhich he has given the name of Protein, (from TrpwTfuw, I am first,) which may be regarded as the commence- ment and starting-point of aU the tissues : the second is, that protein, in every respect identical with that which forms the basis of the three aforesaid animal principles, may be obtained from similar elements in the vegetable kingdom. When the newly-expressed juices of vegetables are allowed to stand, a separation takes place in a few minutes. A gelatinous preci- pitate commonly of a green tinge is deposited, and this, when acted on by liquids which remove the colouring matter, leaves a grayish white siibstance, which has been named vegetable fibrin. It separates from the vegetable juice in which it was originally dissolved exactly as fibrin does from blood. When the clarified juice of nutritious vegetables, such as cauliflower, asparagus, mangel-wurzel, or turnips, is made to boil, a coagulum is formed which it is absolutely impossible to dis- tinguish from the substance which separates as a coagulum, when the serum of blood, or the white of an egg, diluted with water, is heated to the boiling point. This is vegetable albumen. 6 ORGANIC CONSTITUENTS. Vegetable casein is chiefly found in the seeds of peas, beans, lentils, and similar leguminous seeds. Like vegetable albumen, it is soluble in water, but differs from it in this, that its solution is not coagulated by heat. When the solution is heated or evaporated, a skin forms on its sm'face, and the addition of an acid causes a coagulum just as in animal milk. " The chemical anatysis of these three substances has led to the very interesting result that they contain the same organic elements united in the same proportion by weight ; and what is still more remarkable that they are identical in composition Avith the chief constituents of blood, animal fibrin and albumen. They all three dissolve in concentrated muriatic acid, with the same deep purple colour, and even in their physical characters animal fibrin and albumen are in no respect difterent from ve- getable fibrin and albumen. It is especially to be noticed, that by the phrase identity of composition we do not here imply mere similarity, but that, even in regard to the presence and re- lative amount of sulphur, phosphorus, and phosphate of lime, no difference can be observed.'^ ^ When animal or vegetable albumen, fibrin, or casein is to be used for the extraction of protein in a state of purity, the fol- lowing steps are to be taken. The selected substance is suc- cessively washed with water, alcohol, and ether, for the purpose of removing extractive matter, fat, and soluble salts. It is then treated with dilute hydrochloric acid, Avhich extracts the phos- phate of lime and any other insoluble salts that may happen to be present. We now dissolve it in a moderately strong solution of caustic potash, and keep the solution for some time at a tem- perature of 120°, whereby the sulphur and phosphorus that are present form phosphate of potash and sulphuret of potassium. The protein is then to be thrown down from the solution, after filtration, by acetic acid, wliich must be added only in very slight excess, as otherwise the precipitate would be redissolved. It must then be collected on a filter and carefully washed till every trace of acetate of potash is removed. In this state it occurs in the form of grayish white gelatinous flocks, which, when dried, become hard and j'cllow, and give an amber-coloured powder. It is insoluble in Avater, alcohol, and ' Liebig's Animal Chemistry, translated by Gregory; p. 47. PROTEIN. 7 etlier, and is devoid of odour and taste. It readily absorbs moisture, and swells up, but regains its original form upon being heated to 212°. Mulder lias analysed protein from animal and vegetable albu- men, from fibrin, and from cheese or casein ; Scherer has analysed it from animal albumen and fibrin, from the crystalline lens, from hair, and from horn ; and Dumas from animal albumen and casein. The formulae which these chemists have assigned to it approxi- mate closely to each other, although they are not absolutely identical. As Mulder's original formula has been confirmed by the recent investigations of Schroder andVon Laer, we shall adopt it as the correct symbol of the composition of this substance. According to this \dew the composition^ of an atom of protein is represented by the formula C^^ H,, N^ O,^. Its atomic weight is 5529'5, oxygen being 100, and its symbol is Pr. It burns when exposed to the aii', 'nithout leading any ash. When boiled for a considerable time in water, with free exposure to the air, protein becomes slowly oxydised. We shall revert to this sub- ject presently. Protein combines both with acids and bases. It dissolves in all very dilute acids, and forms with them a kind of neutral compound, which is insoluble or nearly so when there is an excess of the acid present. Hence if sulphuric, hydrochloric, or nitric acid be added to a solution of protein in a dilute acid, the protein is precipitated in an insoluble state ; if however the excess of acid is removed by careful washing, the precipitate becomes again dissolved. Acetic acid and the ordinary (tribasic) phosphoric acid constitute an exception to this rule as they dis- solve protein in all proportions. Protein may be precipitated from any of its acid solutions by ferrocyanide and ferridcyanide of potassium, by tannin, by anhydrous alcohol, by various me- tallic salts, and by the alkalies. Tlie Metamorphoses of Protein, a. Sulphuric acid and protein. On the addition of concentrated snlphuiic acid to protein or to any of its modifications (albumen, fibrin, or ' Liebig's formula for protein is Cjg Hjg Ng 0,,. The uumerical results afforded by these formulae approximate very closely. See Appendix I, \ote 1. 8 ORGANIC CONSTITUENTS. casein) a gradual swelling ensues, and the substance assumes a gelatinous appearance. On the addition of water it con- tracts, and it is found to be perfectly insoluble in that fluid. It must be collected on a filter and boiled in water as long as a solution of baryta indicates that any sulphuric acid is being given ofl": it must then be heated with alcohol, and dried at a temperature not exceeding 360°. Tlris is suJj)ho- proteic acid. It appears as a yellow mass, is not easily pul- verized, and is insoluble in water, alcohol, and ether, but dis- solves in potash and ammonia. The salts of silver, copper, lead, and iron yield precipitates Avith the alkaline solutions of this acid. Its formula is C„^ H,, N, O^^, SO3. On the cautious addition of dilute sulphuric acid to an acetic acid solution of protein, we obtain :\Iulder's sulpho-bi-pro- teic acid, which is then thrown down as a flocculent precipitate. After washing it, and diying it at a temperature not exceeding 260°, it assimies a white appearance, and may be easily pulve- rized. With the alkahes it forms solutions from which many of the metallic salts throw down insoluble compounds. Mulder considers that it is composed of tno atoms of protein, two of water, and one of sulphuric acid ; hence it may be expressed by the formula C,„ H,^ N^„ 0,^^ + H,^ 0,^ + 803. If protein (or any of its modifications) be boiled in dilute sulphuric acid, a beautiful purple tint is evolved. (5. Hydrochloric acid and protein. Mulder has formed a hijdro- chloro-protdc acid in the same manner as the sidpho-proteic acid. Its formula is C^„ H,„ N,, 0,^^ + H„ O.^ + H CI. Whe^ protein is boiled in strong hydrochloric acid the solution is at first yellow, but it gradually merges into a blue tint. This change of colour does not occur if the atmospheric air is ex- cluded. y. Nitric acid and pi'oteld. On the addition of nitric acid to protein or to any of its modifications, nitrogen and a little nitric oxide are evolved, oxalic acid and nitrate of ammonia are formed, and there remains undissolved a bright yellow matter, which on being dried assumes an orange tint, and which is known as Xantho-proteic acid. It is devoid of smell and taste, although it slightly reddens moistened litmus paper. It is insoluble in water, alcohol, and ether. It dissolves in strong mineral acids, but is precipitated on the addition of Avatcr ; with the PROTEIN. 9 alkalies it forms dark red soluble salts, and metallic salts throw down yelloAT precipitates. In a state of combination, the for- mula for this acid is Cg^ H„^ N^ Oj„ ; when free it contains two atoms of water. The changes which occur in the production of this acid may be illustrated by the equation — 1 At. Protein . • C,o H3, N, 0„ 3 At. Oxalic acid Ce 0, 2 At. Nitric acid N, 0,„ 1 At. Nitrogen . N 1 At. Water . H 2 At. Ammonia 1 At. Hydrated xantho- He N, proteic acid . C34 H,eN,0„ C40 H32 N, 0,3 C40 H32 Ny O23 S. Chlorine und protein. On passing a current of chlorine gas through a solution of any of the protein-compounds, (albumen, fibrin, or casein,) a white flocculent precipitate is thrown down. After washing it, and carefully drying it at a temperature of 212°, Mulder deduced from it the formula C „ H„ N, O,, -f CI O . He termed it cldoro-proteic acid. It appears from his investi- gations that the protein remains unchanged, but that a portion of the water is decomposed, and that its oxygen combines with chlorine to form chlorous acid (CI O,) while its hydrogen com- bines with another portion of chlorine to form hydrochloric acid (H CI) which remains in solution in the water.' When ammonia is added to the chlorod-proteic acid, the latter substance dissolves, and gives oiF a large amount of nitro- gen. The solution must be evaporated to dryness, and then treated with warm water, which takes up a portion of the residue. On the addition of alcohol to this aqueous solution, a precipitate is thrown down, while muriate of ammonia remains in solution. This precipitate is composed of a substance of great physiolo- gical interest. Its formula^ is C^^ Hg^ N^ O,^ + HO. Mulder originally termed it oxyprotein, but he has recently given it the more descriptive name of tritoxide of protein, without however intending to imply anything more than that it contains three atoms more oxygen than protein. There is another and, in ' That this compound is a chlorite of protein and not a chloride of tritoxide of protein seems certain from its analogy with a corresponding compound of gelatin. ^ See Appendix I, Note 2. 10 ORGANIC CONSTITUENTS. tlieory, a simpler metliod of obtaining tliis compound. When fibrin or albumen of inflamed or healthy blood, of serum of the blood, or of hen's eggs, is boiled with water, after four hours' boiling, principles are always obtained which are soluble in water, whilst the greater part remains undissolved. On repeating the ebullition every four hours with fresh water, fresh quantities of soluble matter are extracted, the insoluble portion becoming poorer in carbon, hydrogen, and nitrogen, but richer in oxygen, until the composition is finally constant. Moreover, the portion of albumen or fibrin soluble in water when evaporated, extracted with alcohol, and treated with cold water, is almost entirely so- luble in it, and likewise contains less carbon, hydrogen, and nitrogen, but more oxygen than protein. The substances taken up by the alcohol are merely products of decomposition of the soluble portion of the fibrin or albumen. It is, moreover, the decomposition of this portion that gives rise to the ammonia that is produced on distilling albumen or fibrin with water. The soluble matter taken up from the fibrin or albumen by prolonged ebullition is in every respect identical with the trit- oxide of protein which we have already described ; it exists moreover ready-formed in the bufiy coat of the blood. From whichever of these sources we procure it, whether from chloro- proteic acid, from albumen or fibrin, by prolonged ebullition, or from the buffy coat of the blood after a comparatively short ebullition, it possesses the same properties. It is soluble in cold water, but not in ether, alcohol, essential or fat oils ; it has nei- ther an acid nor alkaline reaction. It is always precipitated in the same manner from its aqueous solution by diluted nitric, sulphuric, hydrochloric, neutral and basic phosphoric, and tannic acids; by solutions of chlorine, bichloride of mercury, neutral and basic acetate of lead, nitrate of silver, sulphate of zinc, and peroxide of iron. It forms with metallic oxides a class of double salts, which are composed according to the formula (C,o n„ N, 0,, + MO) + (C,„ H,. K 0,^ + IiO). Tritoxide of protein is not precipitated by dilute acetic acid, neutral salts of potash and soda, chloride of barium, hydrochlo- rate of ammonia, nor by that very delicate test for protein, fer- rocyanide of potassium. It dissolves gradually in solutions of potash, soda, and ammonia. When tlioroughly dried, it occurs as an amber-coloured powder. Nitric acid converts it into PROTEIN. 11 xautho-proteic acid, a change which is not produced by the action of that reagent upon chlorod-proteic acid. Let us now revert to the undissolved residue, which ultimate- ly assumes a uniform composition expressed by the formula^ C Q H,. N^ Oj^. It is this which is first formed from protein by the influence of the oxygen of the atmosphere. The other sub- stance (tritoxide of protein) originates from it by the addition of another equivalent of oxygen. In this respect albumen and fibrin give different results. Albumen, without going through this preparatory change like fibrin, is at once converted into trit- oxide of protein by ebuUitiou, the insoluble portion which re- mains being unaltered albumen. From the composition of this insoluble portion it has received the name of biuoxide of protein. It exists ready formed in the huffy coat of the blood. Yon Laer has obtained it from hair in the folloT\-ing manner. The protein is first thrown down by the addition of a little acetic acid to a solution of hair in potash. On the addition of a larger proportion of free acid, after the removal of the protein, another substance, previously in a state of solution, is thrown down. This is the biuoxide of protein. Von Laer describes it as a bright yellow precipitate. After being carefuUy washed and dried it forms a black, glossy resinous mass, which on being pulverized forms a dark amber- yellow powder. It is insoluble in water and alcohol, but dissolves perfectly in dilute acetic, hydrochloric, nitric, and sulphuric acids. It does not assume so strong a yellow colour as protein, when treated with nitric acid. Ferrocyanide and ferridcyanide of potassium, and acetate of lead precipitate it from its acid solutions. It is soluble in potash and ammonia. If the biuoxide of protein be treated with chlorine there is formed, at a loss of one atom of nitrogeu, and a gain of three of oxvgen, a new substance C^„ H„ N O,., to which no name has yet been assigned. In order to obtain these products of oxidation of protein by boihng fibrin in water, it is essentially necessary that there shoidd be free access to the atmospheric air. ' See Appendix I, Note 3. 12 ORGANIC CONSTITUENTS. The products of the oxidation of protein occur constantly in the blood; they are formed in the lungs from fibrin, a sub- stance which has been shown by Scherer to possess the pro- perty of absorbing oxygen when in a moist state. The fibrin, oxidised in the lungs is, according to Mulder, the principal, if not the only, carrier of the oxygen of the air ; it is especially this substance from which the secretions are formed. In inflammatory conditions, a considerably larger quantity of protein in an oxidised state, is contained in the body, than is found in a normal state. ^ These compounds (or at least one of them) are also found in pus, the substance termed pyin being in reality tritoxide of pro- tein ; in false membranes, in cooked meat, and in vitelline sub- stance; in the last-named substance we meet Avith a sulphuret of the binoxide of protein. Mulder has recently obtained a third oxide of protein, repre- sented by the formula C^„ H^^ N^ O,^^, by boiling yeast in water. It occurs in a state of solution. ' The examination of the foregoing facts leads to some very important conclusions. "We see, for instance, that, by the ebullition of meat, protein is converted into two oxides, and is thus no more presented to the organism as a means of nutrition in the form of protein, but one part is converted into binoxide, which is hard and sparingly soluble, while another portion is clianged into the soluble tritoxide, and occurs in broth, extract of meat, &c. According to Mulder, the interior of roasted meat un- dergoes a change analogous to that which is produc(id by ebullition. As the effects of ebullition upon albumen differ from those on fibrin, in evolving only the tritoxide of protein, boiled albumen must be perfectly distinct from boiled or roast meat as a means of nourishment. The process of inflammation also appears essentially as a higher grade of oxida- tion. The albumen of the blood, which furnishes only tritoxide by ebullition, pro- bably takes no part in the change : we may conclude that it is effected by the fibrin alone, which, as we know, absorbs oxygen from the air, and is with so much compa- rative facility converted into binoxide and tritoxide of protein. Diu-ing the height of inflammation, there is a great excess of the oxides of i)rotein in the blood; in a state of health they are, doubtless, present, but in much smaller proportions. Between these extremes there may be many intermediate states induced by different disor- ders. Respiration may consequently be regarded as a true oxidation of the blood, or rather of the protein ; and in inflamniiition, in Mhich the blood contains a greater quantity of binoxide and tritoxide of protein than in the healthy state, this body becomes more thoroughly oxidised. Hence it occurs that, in the acceleration of the act of respiration, in fevers, for example, inflammation so easily supervenes after any violent or sustained efforts. Every paroxysm of fever must necessarily cause the formation of a greater quantity of oxidised protein in the system, and every augmen- PROTEIN. 13 £. Potash and protein. On the addition of protein to a concen- trated solution of potash^ and submitting the mixture to ebulli- tion decomposition takes place, and a crystalline substance, two distinct extractive matters, and formate and carbonate of am- monia are produced. After the alkaline solution has been neu- tralized as completely as possible by sulphuric acid ; the formic acid may be removed by gentle distillation. On evaporating the mixture to about one third of its volume, the greater part of the sulphate of potash will separate in a crystalline state. After its removal, the fluid which is of a reddish brown colour must be reduced to the consistence of an extract, and then treated with boiling alcohol, which will take up everything except any sulphate of potash that may have escaped previous removal. As the alcoholic solution cools, erythroprotid is depo- sited, in the form of a reddish brown extract. It is readily solu- ble in water, and in boiling, but not in cold, alcohol ; and it is precipitable from its aqueous solution by the salts of lead, silver, and mercury, of a rose-red colour : it is also precipitable by tannic acid. From an analysis of the combination of erythro- protid with oxide of lead, Mulder has estimated its composition^ at C,3 H^ N O. Subsequently to the deposition of erythroprotid, leucin se- parates in a crystalline state. It occurs in brilliant plates or scales, somewhat resembling cholesterin. It cranches between the teeth, is inodorous and tasteless, and sublimes unchanged tation in tlie amount of oxidised protein must produce inflammation, whicli may in its turn determine fever. Hence also it happens that stimulating foods and drinks, whicli quicken the respiration, or cold air, which introduces more oxygen iuto the lungs, often give the first impidse to the development of inflammation in the organism. The biiiFy coat is formed when the oxides of protein predominate in the blood ; when they accumulate in any particular part of the system, local inflammation is the result. In the latter case, morbid products, e.g. false membranes, &c., are evolved, which are found on analysis to be in a great measixre composed of oxidised protein. Now inflammation must be combated by endeavouring to diminish the quantity of the tritoxide of protein, and to hinder its formation in the lungs. Venesection proves antiplilogistic by directly diminishing the tritoxide of protein : increased secretion of the aUmentary canal indirectly produces the same effect by accelerating the change of substance in tlie body, and consequently also the consumption of a greater quan- tity of protein and its oxides. ' See Appendix I, Note 4. 14 ORGANIC CONSTITUENTS. at about 340°. It contains no water of crystallization. It is soluble in water and in alcohol^ but not in ether : its formula^ is C,^ H,, N 0_j. According to Mulder it must be regarded as an integral constituent of protein. It combines with nitric acid and forms a crystalline acid to which the term nitro-leucic acid has been given. We shall have occasion to revert to leucin in our observa- tions on gelatin. Protid is the term applied to the extractive matter that re- mains in solution after the removal of the erythroprotid and leucin. It is of a briglit yellow colour^ easily pulverizable, and soluble in water and alcohol without colouring them. It is pre- cipitable by the basic acetate of lead, but not by any other me- tallic salts nor by tannin. The salts of lead serve to distinguish it from erythroprotid. If a mixture of these two substances be dissolved in water, the latter is precipitated by the neutral, the former by the basic acetate of lead. Its formula2 is C„ H„ NO . The action of caustic potash on protein is evidently very com- plicated. Mulder endeavours to show by the following formula how these metamorphoses may occvir. 2 At. Erythroprotid 2 At. Protid 2 At. Leucin 4 At. Ammonia . 2 At. Carbonic acid 1 At. Formic acid C.6 H,e N, 0„ C,, H,, N, O3 H.. N, C, O, C. H O3 *^80 "71 ^10^33 2 At. Protein 9 At. Water ^80 Hea N,Q Oj Ho Oo Ceo H„ N.„ O3 According to Liebig, protein is produced by vegetables alone, and cannot be formed by animals, although the animal system has the power of converting one modification of protein into another ; it is never found as protein, in nature ; but occiu-s in the shape of albumen, fibrin, or casein, both in vegetables and animals. These modifications of protein are employed in the formation of the different tissues, each of which bears a simple relation to that substance, as will be seen by the following table: — ' See Appendix I, Note .5. * Ih. Note 6. ALBUMEN. 15 Albumen of the blood Albumen of the egg Fibrin Casein Globulin Muscular flesh Arterial membrane Mucus Chondrin Horny tissue Gelatinous tissue = 10Pr + SjP = 10Pi- + S P = 10 Pr + S P = 10Pr + S = 15 Pr + S = P^+ HO + n = Pr + 2 HO = p7+ 3 HO = Pr + 4 HO +2 =:P7_+ NH3 + 30 = 2 Pr + 3 N H3 + H + 7 0. We do not mean to assert that tliese formulae represent the actual constitution of the respective tissues^ but only that they give the proportion of elements actually present, and show how they might give rise to those tissues. Some of these tissues con- tain protein, or at least yield it by the action of potash, whilst others, as for instance the gelatinous tissues, although doubtless derived from protein compounds, do not contain it, and conse- quently cannot yield it. Diagnosis of protein. Its insolubility in water, alcohol, and ether, and its precipitation from an acid solution by the ferro- cyanide and ferridcyauide of potassium are sufl&cient. 2. Albumen. This important modification of protein forms the white of eggs, and occurs in large quantity in all the animal fluids that contribute to the nutrition of the organism. It is also found in most of the animal solids, and in nearly all morbid products. We have abeady adverted to its existence in the vegetable kingdom. Albumen is naturally soluble in water, and it is found dis- solved in the serum of the blood, in vegetable juices, &c. But when it has once been submitted to a certain degree of tem- perature, or to the action of various chemical reagents, it assumes the coagulated state, and becomes insoluble in water. Soluble albumen. Soluble albumen may be obtained in a solid form by evaporating to dryness, at a temperature not ex- ceeding 120^, the serum of the blood, or white of egg. The dry mass is yellow, partially transparent, hard, and tough ; it must 16 ORGANIC CONSTITUENTS. be reduced to a fine powder, and treated successively with ether and alcoliol. By these means Ave succeed in removing nearly all foreign bodies from the albumen, which when dried exhibits a white or pale yellow colour, is devoid of taste and odour, and presents a neutral reaction. If perfectly dry, albumen in this state may be exposed to a temperature of 212 without passing into the coagulated condition. When digested in cold water, it gradually swells up, and finally dissolves, forming a mucilagi- nous, colourless, and insipid fluid, which on being heated to 140° begins to give indications of coagulating : if the solution is very dilute, the temperatui'c may be raised to 165 with the occurrence of this change, and when present in very small quantity the albumen may not separate till the fluid boils, or even until the ebuUition has been prolonged for a short time. When albumen is analysed, it yields the same results as protein in regard to carbon, hydrogen, nitrogen, and oxygen, but it also contains a small quantity of phosphorus and sulphur, (less than 1 o together,) which are absent in protein. According to Mulder's analyses, i the albumen of eggs may be represented by the formula C^'„^ PL,^ N^^ O,,^, SP + or 10 Pi^ + SP, which, as we shall presently see, is identical wdth the formula for fibrin. The albumen of the blood difl'ers from this, in containing one additional atom of sulphur ; its formula is 10 Pr + S^ P. Most of the chemical observations on protein apply equally to albumen, and therefore without entering into any description of the various chemical changes that occur upon the addition of reagents, we shall simply notice the' physical appearances pre- sented on the application of the ordinary tests. Albumen is precipitated from its fluid solutions by all the ordinary acids, with the exception of acetic, tartaric, and phos- phoric (tribasic) acids ; which not only do not precipitate it, but check the ordinary precipitation induced by heat. It is precipitated from its solution in these acids by ferrocya- nide and fcrridcyanide of potassium, the former of which yields a white, and the latter a yellow, precipitate. These pre- cipitates are soluble in alkalies but not in acids. When these two substances are used as tests, their action may be im- peded by the presence of free soda or its carbonate; the addition ' See Apppiirlix I, Note 7. ALBUMEN. 17 of a few drops of acetic acid is therefore always advisable in this case. Bichloride of mercury, and nitrate of the black oxide of mercuiy throw down whitish precipitates. Either of these tests will detect the presence of ^ji^ part of dry albumen. Precipitates of various colours and appearances are thrown do^vn by sulphate of copper, nitrate of silver, the acetates of lead, protochloride of iron, alum, tannin, creosote, alcohol, &c. The precipitates which the metallic salts throw down with albumen are usually mixtures of two distinct substances, one a compound of albumen with the acid, the other a compound of albumen with the metallic oxide ; the former is usually some- what soluble, the latter insoluble. The alkalies and their carbonates form soluble compounds with albumen, and frequently require to be neutralized before the ordinary tests can be efficiently used. The tests in most general use are heat, and nitric acid. When they both produce turbidity or a precipitate, the existence of albumen may be considered as proved.* Coayulated albumen. Coagulated albumen may be obtained by submitting the white of egg or the serum of the blood to a temperatm'e of from 160'' to 180° ; 167° according to Simon. The coagulated mass must be then rubbed in a mortar, and successively digested in water, alcohol, and ether, until all substances soluble in those fluids are removed : it must then be carefully dried. When obtained in this manner, it usually contains from 1 to 2% of phosphate of lime, an earth which soluble albumen seems to have the power of dissolving. In order to obtain it free from this impurity, the follo^ving process may be employed. Coagulate albiimen with dilute hydrochloric acid, wash the precipitate with water acidulated with the same acid, and then add so much cold water as may suffice to dissolve it. On the addition of carbonate of ammonia, co- agulated albumen is separated as a flocculent, white precipitate. To remove any fat that may be present, it should be digested in hot alcohol or ether. When dry, it is yellow and transparent ; it swells upon being placed in water, but is only very slightly soluble in it. In its ordinary chemical relations it resembles protein. ' An apparent exception in the case of the urine will Ije suhsequentlv noticed. 2 " 18 ORGANIC CONSTITUENTS. Albumen always contains more or less salts^ pliospliate and sulphate of lime, cliloride of sodium, and probably some lactates. Their amount is variously estimated by different chemists : the average is about 4 to 8^. In the albumen of the egg ISIulder found 0-3^, and in that of blood, 0-42 of sulphate of lime. The development of the young animal in the egg of the bird during incubation affords a striking illustration of the physiological import of this substance. It is easily shown that the egg contains no nitrogenous compound except albumen. The albumen of the yelk has beenproved, by the analyses of Bence Jones and Scherer, to be identical with the albumen of the white ; and in addition to this the yelk only contains a yellow fat with traces of iron. Yet we see in the process of incuba- tion, during which no foreign matter, except atmospheric air, can be introduced, or can take any part in the development of the animal, that feathers, claws, blood-corpuscles, fibrin, cellular tissue, and vessels are produced. Diagnosis of albumen. It coagulates at 167°. It is not precipitated by acetic or dilute sulphuric acid, and from these acid solutions it is precipitated by ferrocyanide of potassium. Corrosive sublimate and nitric acid throw down copious de- posits. 3. Fibrin. This modification of protein occurs in two forms, dissolved and coagulated. The former occurs in blood, lymph, chyle, juices of plants, &c., as long as these fluids form a part of the li\dng organism ; on their w ithdrawal from the influence of the vital force, the fibrin speedily coagulates. It is found in both these states in the animal and vegetable kingdoms. The best method of obtaining it for chemical examination is either by briskly stirring newly-drawn blood with a little bun- dle of twigs, or else by shaking it in a stoppered bottle with a few bits of lead or tin. The fibrin adheres to these substances in the form of a nearly colourless coagulum. This must be washed in cold water till it ceases to give off any colour what- ever ; it must then be treated with boiling ether, in order to remove the fat which is always associated with it. When dried, it assumes a pale yellow colour, is devoid of FIBRIN. 19 taste and odour, and is insoluble in water, {jlcohol, and ether. AYlien placed in water it sinks ; it speedily absorbs a portion of the fluid, swells up, assumes its original bulk, and increases its weight threefold. The composition of fi.brin is represented bv the formula' C,opH3„N,, O,,, SP, orlOPrisP. The observations which have been made respecting the action of acids and alkalies on protein apply equally to fibrin. Fibrin is stated to have the power of decomposing binoxide of hydrogen catalytically with the evolution of oxygen and heat. According to Scherer this action is induced by fresh fibrin from any source, but not by boiled fibrin. This power is not possessed by albumen. A concentrated solution of nitrate of potash dissolves humid fibrin in the course of twenty-four hours, and gives it the pro- perties of albumen. (Denis.) This observation requires further confirmation ; it has failed in the hands of Simon and other chemists, and it is not impossible that the phenomena described by Denis were due to the presence of some uncombined potash. The average quantity of fat associated with fibrin was found by Simon to vary from 2 to 4JJ, which agrees closely with the results of other observers. Fibrin always contains a certain amount of salts, especially of the phosphate and sulphate of lime : the former seems to be chemically combined with it. The amount, according to Simon, lies between 1-5 and 2",. Diagnosis of fibrin . Fibrin is distinguished by its spontaneous coagulation, by its insolubility in water, alcohol, and ether, and by its precipitation from acid solutions by ferrocyauide and ferridcyanide of potassium. 4. Casein. This substance constitutes the most important ingredient in the milk of the mammalia. We have already shown that it also exists in vegetables. Casein may be obtained with facility by either of the following methods, ' See Appendix 1, Note 8. 20 ORGANIC CONSTITUENTS. a. Evaporate milk to dryness in the water-bath ; triturate the sohd residue and treat it with boihng ether, as long as it gives off any butter. When this ceases to be the case, remove the butter, and evaporate off the ether ; dissolve the residue in water, and filter. On the addition of alcohol to the clear filtered fluid, the casein is separated and thrown down. In order to remove any sugar of milk that may be entangled with the casein, the precipitate may be redissolved in water, and again thrown down by alcohol ; if it be now collected and dissolved in water, it affords a tolerably pure solution of casein. b. Casein may also be obtained by the addition of sulphuric (or any other) acid. Sulphfite of casein is precipitated, which must be carefully washed in water, freed in the ordinary manner from butter, &c. and then digested with carbonate of lime. By careful and, if necessary, repeated filtration we obtain a clear solution, which however is not free from lime. A solution of casein prepared according to either of these methods is possessed of little flavour; on the application of warmth it evolves a milky odour, and during evaporation it becomes covered with a skin or film, which on being removed is speedily renewed. This skin is due to the action of oxygen, for it does not form in an atmosphere of carbonic acid. By a continuance of the evaporation we ultimately obtain a residue of dry casein. It appears as a brittle yellow substance. It does not admit of being perfectly dissolved in water, in con- sequence of a portion of it having assumed an insoluble condi- tion during evaporation. According to Mulder^ casein is represented by the formula C,ooH3.„N,„0,,, SorlOp^ + S. The action of milk in the nutrition of young animals proves that casein is capable of being converted into albumen, and fibrin ; while the production of milk in an animal fed on albu- men or fibrin shows that these substances may be reconverted into casein. The alkahes exert a similar solvent power over casein as over protein and its other modifications. The metallic salts also form similar double compounds. It differs from albumen, in being precipitated by all acids. The latter reagents must be ' See Appendix I, Note 9. CASEIN. 21 applied cautiously, as casein is soluble in an excess of many acids. On the addition of ferrocyanide or ferridcyanide of potassium to a perfecth'^ neutral solution of casein, a slight precipitate is observed ; if the solution is alkaline there is no perceptible effect, but if it is first rendered acid by a little acetic or dilute sul- phuric acid, a copious precipitate is thrown down by both tests. The casein of cow's milk is thoroughly precipitated by the mucous membrane of the calf's stomach ; on the addition of this reagent to woman's milk, imperfect coagulation sometimes oc- curs ; in other cases no apparent action is produced ; the coagu- lation is never perfect. In this case the mucous membrane of the child's stomach produces a more energetic effect than that of the calf. If a quantity of potash or ammonia be added to the milk, sufficient to give it a decidedly alkaline reaction, no coagulation is effected. Rochleder has recently attempted to show that pure casein is a substance nearly insoluble in water ; that the so-called soluble casein is a combination of casein with potash, soda, or lime ; and that the coagulation of the soluble casein by acids is nothing more than a separation of the casein, resulting from the combination of the acid with the base of the casein com- pound. In this manner, he explains how solutions of potash prevent coagulation, when added in very small quantity to milk, and why (especially in warm weather) very slight causes are able to produce a coagulation of the milk ; as only the smallest quantity of lactic acid is required to be formed, in order to neutralize the minute traces of soda, which are able to retain in a state of solution an enormous quantity of casein. Coagulated casein is found in the milk, constituting the walls of the butter-vesicles. For the piirpose of chemical investiga- tion, it is best obtained by the addition of anhydrous alcohol to a solution of casein. When dried, it is hard, yellow, and transparent. In its chemical relations it closely resembles coagu- lated albumen. The amount of ash left after the incineration of casein seems to vary considerably. Mulder estimates it at o*8", and Simon at 7^, in the casein of cow's milk. In casein from the milk of woman, Simon estimated it at 5"^. Uochleder, whose experi- ments were made under the direction of Liebig, found that pure 22 ORGANIC CONSTITUENTS. casein left only O'S",. The asli contains phosphoric^ carbonic, hydrochloric, and sulphuric acids, in combination with lime, and traces of magnesia and iron. Diagnosis of casein. Casein may be distinguished from albu- men by its not coagulating at 167°, and by the skin which forms on its surface during evaporation. It is precipitated by all dilute acids, and redissolves in an excess of the test. It is thrown down from its acid solutions by ferrocyanide and ferridcyanide of potassium. Casein of woman's milk is less perfectly thrown down by dilute sulphuric, lactic, and hydi'o- chloric acids, than the casein of cow's milk. Simon has obtained a modified form of casein from the crys- talline lens,i from tubercle, pus, and saliva. It may be recognized as casein by the diagnosis which has been given, but it difiers from human casein in its thorough precipitation by all acids ; and from the casein of human and cow's milk byits greater solubilityin hot alcoholof 0*915 — 0'925. The globulin of Berzelius, which together with hcematin forms the blood- corpviscles, is considered by Simon as a peculiar form of casein. Very little is known regarding it, further than that it is a protein-compound. Mulder^ represents it by the formula 15 Pr+S. It must not be confounded with Lecanu's globulin, which is merely impure hsematin mingled with some albumen. Pepsin, Ptyalin, Chondrin, Glutin, Pyin. 5. Pepsin. This name (from Tmrai^, digestion) was given by Schwann, to a substance which constitutes the most essential portion of the gastric juice. The following directions for the preparation of pepsin are taken from Vogel's essay on the sub- ject ', they correspond in nearly every respect, with the method which was given by Wasmann, who has the credit of first obtain- ing it in an isolated state. The glandular membrane of the fresh stomach of the hog, is separated, and after being cut into small pieces, is treated with cold distilled water; after twenty- four hours' immersion, the water is poured off, and a fresh quan- tity added. This operation is repeated for several days, until ' See Appendix T, Note 10. ^ II). Note 11. PEPSIN. 23 a putrid odour becomes perceptible. Tbe aqueous infusion tlius obtained is precipitated with acetate of lead, which causes a white flocculent deposit, containing the pepsin mixed with much albumen ; this precipitate is difi'used through the water, and must be decomposed by sulphuretted hydrogen. When the liquor is filtered, the solution contains pepsin and acetic acid, while coagulated albumen and sulphuret of lead remain on the filter. In order to obtain solid pepsin, the filtered liquid is evaporated to the consistence of a syrup, at a very moderate temperatm'e (according to Wasmaun, not higher than 95), and absolute alcohol is then added to it. After some time a whitish bulky precipitate is formed, which is to be dried by exposure to the air ; it then constitutes a yellowish viscid mass of a pecu- liar animal odour, and a disagreeable taste. Pepsin thus ob- tained has an acid reaction, because it always contains a small quantity of acetic acid. This is most efficacioush' removed by heating the pepsin for some hours in a salt-water bath ; by which means a white powder, soluble in water and possessing no acid reaction, is obtained. The action of a high temperature injiu'cs the digestive power of pepsin, but does not affect its chemical composition. From Yogel's analysisi of this substance, it appears that it may be very nearly represented by the formula C^^ H^,, N^ 0^^^. On comparing this with Liebig's formula for protein, it appears that pepsin may be formed from protein by the subtraction of two atoms of water, and the addition of two atoms of nitrogen. The most remarkable property of pepsin is the power which its aqueous solution, when slightly acidulated, possesses of dis- solring the jjrotein-compounds. A solution containing only goigo part of pepsin, and slightly acidulated, will dissolve coagu- lated albumen in six or eight hours. This property is appa- rently destroyed by the alkalies. Sulphuric, hydrochloric, and nitric acids, when added in very small quantity to a solution of pepsin, throw dovai white flocculi, which redissolve in an excess of the test : on the addition of still more acid the precipitate again occurs. Acetic acid throws down a precipitate which redissolves in an excess of the test ; no second precipitate is thrown down by the addition of more acetic acid. ' See Appendix I, Note 12. 24 ORGANIC CONSTITUENTS. Pepsin is thrown down from its aqueous solution by bichloride of mercury, acetate of lead, the sulphates of iron, sulphate of copper, and perchloride of tin. Ferrocyanide of potassium throws down no precipitate from an acidulated solution of pepsin. Pepsin, which is precipitated from a concentrated aqueous solution by anhydrous alcohol, is said to lose its digestive power. According to Liebig, pepsin as a distinct compound does not exist ; he ascribes the solvent power of the gastric juice to the gradual decomposition of a matter dissolved from the mem- brane, aided by the oxygen introduced in the saliva. (Animal Chemistry, p. 109 et seq.) Diagnosis. Pepsin is soluble in water, insoluble in absolute alcohol and ether; it is known by its precipitation by dilute acids, by the precipitate being redissolved in a slight excess of the test, and by the non-occurrence of a precipitate on the ad- dition of ferrocyanide of potassium to the acid solution. It is fui'ther distinguished from albumen by its being precipitable by acetic and dilute hydi'ochloric acids. 6. Ptyalin. This term has been applied to a peculiar animal matter that exists in the saliva. The following is the best me- thod of obtaining it. Fresh saliva must be neutralized with acetic acid, and then evaporated on the water-bath ; the residue must be extracted first with alcohol,^ and then with spirit. The ptyalin will remain undissolved amongst the protein-com- pounds, and must be extracted from them by the addition of water, in which it is readily soluble, and with which it forms a viscid fluid. The evaporation of this aqueous solution yields ptyalin free from all animal matters, but containing a trace of salts. When dry it is colourless, transparent, and brittle, devoid of odour, but with rather a sickly taste. It is readily soluble in water, but is insoluble in alcohol and ether. It is precipitated from its aqueous solution by alcohol, but not by the mineral acids, metallic salts, acetic or tannic acid. Our knowledge of this substance is by no means accurate ; no analysis has ever been puljlished, and there is no doubt that ' The term xphit is used to denote aleoliol of spec. grav. -833, which coiitaius about ST);^ of anhyihous alcohol ; by alcohol, aiihydious alcohol of spec. grav. -792 is imiilied. GELATIN— CIIONDRIN. 25 all the animal fluids yield an extract to water, wliicli strongly resembles, if it be not altogether identical with, ptyalin. Diagnosis. Ptyalin may be distinguished from the protein- compounds by its indifference to ferrocyanide of potassium ; and from pepsin by its non-precipitation by dilute acids. 7. Gelatin — Chondrin and Glutin. Under the term gelatin we include the organic tissue of bone, cartilage, sinew, ligament, skin, cellular tissue, and serous membrane. All these substances dissolve by long continued boiling in water, and the solution on cooling assumes a consistent gelatinous mass. It is represented in various degress of purity by glue, size, and isinglass. Gelatin does not exist as gelatin in the animal tissues, but is formed from them by the action of boiling water. ]\Iiiller has shown that there are two (if not three) distinct forms of gelatin. To that which is obtained from the permanent cartilages, the cornea, fungous bones, &c. the term chondrin is given, while glutin in- cludes those forms of gelatin which are obtained from skin, serous membrane, hoof, bone, tendon, fibrous and spongy carti- lage, cartilage of bone, &c. As chondrin and glutin differ not only in the sources from which they are derived, but also in many of their chemical characters, we shall consider them separately. Chondrin is most easily obtained by boiling any of the per- manent cartilages, as for instance those of the ribs, larynx, or joints, for about twenty-four hours, in Avater : the solution must then be strained, in order to remove any coagulated matters, and allowed to gelatinize ; it must then be di*ied at a low heat. In this state it is hard and brittle, colourless and transparent. It sinks in cold water, and swells very much, without dissohdng. Scherer has deduced from his analyses the following formula^ for chondrin, C^^ H^^^ N^ O.,^, which corresponds numerically with Pi- + ^ HO + 0,,.2 Its formula, according to Mulder, is C^,,^ H^^^^ N^^ Oj^^ S, or 20 (C,g H,3 N, 0.) + S. When burned it leaves about 4^ of phosphate of lime. Chondrin is precipitated from its solution, and notredissolved in an excess of the test, by acetic acid, tannin, the neutral and basic ' See AppeudLx I, Note 13. ^ Deduced from Liebig's formula. 26 ORGANIC CONSTITUENTS. acetates of lead, sulphate of iron, clilorine, iodine, and bromine. The following substances also give well-marked precipitates, which are, however, soluble in an excess of the test, alum, sulphate of copper, nitrate of silver, perchloride of iron, and nitrate of the protoxide of mercury. Creosote produces an immediate tur- bidity, and renders a solution of chondrin gelatinous in the course of twelve hours. Alcohol throws down chondrin from a concentrated solution, in the form of a white, viscid, and tenacious mass. Ferrocyanide and ferridcyanide of potassium throw down no precipitates when added to an acid solution of chondrin. Glutin may be obtained in a state of purity from common glue, of which it forms the chief ingredient. On placing glue in cold water it absorbs moisture, and swells into a tremulous jelly, but does not dissolve. The cold water must be changed as long as it continues to take up anything from the glue. The glue, after undergoing this purification, must be heated till it is perfectly fluid, and then strained through a cloth or coarse filter. It ge- latinizes on cooling, and when dried represents pure glutin. In its physical characters it is nearly identical with chondrin, but is usually rather more coloured. It is represented by the for- mulai C,3 H,p N,^ O^. (Mulder.) Scherer assigns to it the formula C,,^ H^„ N,. O,^, Avhicli is numerically equal to 2 Pr + 3 NH,^ + HO + 70, but recent investigations tend to show that this formula gives an excess of hydrogen. When burned, glutin leaves a slight ash, consisting chiefly of phosphate of lime. By long continued boiling, glutin loses its power of gelatinizing ; in this state its ultimate composition may be represented by the formula C^,,^ H^, N^ O.^, or 4 (C,3 H,„ N^ OJ + HO. In other words, it appears to be changed into a compound, in which four equivalents of glutin are united with one of water. If a stream of chlorine be passed through a solution of glutin, a compound of chlorous acid and glutin is obtained, w^hich is analogous in type with the preceding substance. It is represented by the formula 4 (C,, H,^ N,, O.) +C1 O,. This is the compound re- ferred to in the note to page 9. The most important test for gelatin (either glutin or chondrin) is tannin, which will precipitate it when diluted 5000 times. ' See Appendix I, Note 14. GLUTIN. 27 Three different compounds of gkitin and tannic acidi have been discovered, and submitted to analysis ; they are, ho^yever, indi- vidually of no particular importance in a physiological point of view. The extreme facility witli Avhich tannin precipitates ge- latinous matters gives a clue to the medicinal action of astringent drugs on the human organism. They at once form insoluble compounds, (for tannin acts similarly on the protein-compounds,) and do not enter the blood ; and this is the reason of their being comparatively innocuous. According to Mulder a less amount of tannin than is contained in one ounce of cinchona bark would, if conveyed directly into the blood, cause instantaneous death. Acetic acid produces a slight turbidity, which speedily dis- appears on the addition of an excess of the test. Alum either produces no visible effect, or else throws down a very slight precipitate, which soon disappears, and the other salts, which have been mentioned as reagents for chondrin, yield no (or at most, very slight) precipitates with glutin. Alcohol and creosote act much the same as on chondrin, and no precipitate is occa- sioned by the ferrocyanide or ferridcyanide of potassium. On boiling glutin in an excess of caustic alkali, till ammonia ceases to be developed, sugar of gelatin (glycicoU) and leucin are produced in the ratio of four parts of the former to one of the latter. In order to separate these substances, the alkaline solution must be saturated with sulphuric acid, evaporated to dryness, and the residue boiled with alcohol. The leucin being more soluble in alcohol than the glycicoll may be extracted from the evaporated alcoholic solution by cold alcohol; the glycicoll will remain in an impure condition in the residue. On treating glutin with concentrated sulphuric acid a colour- less fluid is obtained, which, after prolonged boiling and satu- ration with carbonate of lime, yields, in addition to certain un- investigated compounds, leucin and glycicoll. This method is stated by Mulder to yield a less quantity of glycicoll, in pro- portion to leucin, than the former. Glycicoll crystallizes in colovirless prisms from a solution in alcohol, and in rhombs from a spirituous solution. These crystals possess a very sw^eet taste, are perfectly neutral, resemble cholesterin in their appearance, dissolve in 414 parts of water and in 931 of alcohol. ' It must be remembered that tanuiii and tannic acid are svnonvmous terms. 28 OBGANIC CONSTITUENTS. The composition of glycicoll is represented bv the formula' C, H^ N, Ojor C, H, N, 0^ + 2 HO. It is worthy of remark that on subtracting an equivalent of grape or diabetic sugar fi'om two equivalents of glycicoll, we obtain the elements of two equivalents of urea : 2 (C, H^,N, O,) — C,, H,, O,, = 2 (C, H^ N, OJ The oriffhi of glut in in the animal organism is still unknown. As no traces of it have ever been discovered in the vegcta))le kingdom, we cannot suppose that (like protein) it arises from that soiu'ce. In all probability it is formed by the action of alkalies on protein ; since we know that protein, submitted to such influences, yields products which in their chemical compo- sition approximate closely to glutin, and that the blood is suffi- ciently alkaline to effect such, or similar, modifications. In the hair, we find, associated with bisulphuret of protein Pr + 2 S, a connecting tissue, G^^ H^^, N3 O^, which differs from glutin, C,3 H,jj N^ O^, simply by one atom of nitrogen. Moreover protid, Cj^ H^, N O^, and erythroprotid, C,^ H^ N O,, nearly resemble glutin in their composition, and both glutin and the protein-compounds yield leucin when treated with caustic potash. These facts render it in the highest degree probable, that glutin is formed in the organism, from the decomposition of protein by alkalies ; much as protid and erythroprotid are produced in the laboratoiy. A reference to the symbolical illustration in page 14, will show that with every two equiva- lents of ammonia that are developed, there are produced one equivalent of protid, C,^ H^ N O^, and one of erythroprotid C, J H^ N O^. If Ave add to each of these the elements of one equivalent of ammonia, we obtain C.. H,^ N, O, and C„ H„ N^ 0„ It only remains for us to assume that the oxygen which is con- tinually acting on the blood in the lungs, yields three equiva- lents of oxygen to the former, and one to the latter of these substances, and we have from the protid, C.,.H„N,0, + 0, or C,3H,„N,0^ + 2HO; and from the erythroprotid, C,3 H,. N,^ 0, + or C,, H,„ N^ 0,-f HO ; that is to say, glutin and water may be supposed to be formed ' See Appendix I, Note 15. PYIN. 29 from protid and eiythroprotid by tlic ammonia, whicli the alkali of the blood evolves from the protein-compounds, with the cooperation of the oxygen of the atmosphere, in the lungs. ^ In the present state of organic chemistry, it is impossible in most cases, to state with certainty how changes such as these take place ; we can only indicate the possible, and the most prolKible methods. That the gelatinous tissues are evolved from protein-compounds, in some manner or other, cannot admit of a doubt. From what other source can they be derived in the chick, but from the protein-compounds of the egg ? That chondrin and glutin, the two principal forms of gelatin, are closely alHed to protein, is sufficiently clear. They will not however jaeld protein, Avhen acted on by potash; neither do they produce a pm'ple colour \viih hydi'ochloric acid. Con- sequently they do not contain protein. Hence it is that ani- mals fed exclusively on gelatin, die with the symptoms of star- vation, for the gelatin cannot yield albumen, fibrin, or casein ; and the animal system, although it has the power of converting one protein-compound into another, does not possess the power of forming protein from substances which do not contain it. Consequently blood cannot be formed from gelatin, and the animal soon dies. The probable uses of a mixed gelatinous diet for convalescents, are pointed out by Liebig in his ' Animal Chemistry,' pp. 98-9. Diagnosis. Chondi'in and glutin may be recognized by their property of gelatinizing on cooling, and by the energetic action of tannin on their solutions. Ferrocyanide of potassium added to an acidulated solution of these substances, serves to distinguish them from the protein-compounds; and either acetic acid or alum will suffice to distinguish chondrin from glutin. 8. Pyin. This term was applied by Giiterbock to a pecu- liar substance which occm's in pus, and which he isolates in the following manner. He precipitates the pyin, together Avith albumen, from pus, by the addition of strong alcohol. The ' The recent investigations of Enderlin, showing that there is no free alkali in the blood, but that its alkaline reaction is due to tribasic phosphate of soda, tend to throw considerable doul)t on the ingenious hypothesis of Mulder, given in the text. It must also be remembered that leucin, protid, and erjihroprotid have never yet been detected in the animal organism. 30 ORGANIC CONSTITUENTS. precipitate is treated with water, which dissolves the pyin : any albumen that may be dissolved at the same time, can be coagu- lated by heat, and removed by filtration ; and in this manner a tolerably pure solution of pyin is obtained. Vogel did not succeed in obtaining it ; and from Simon's researches it would hardly appear to be a constant constituent of pus, and purulent sediments. Pyin is soluble in water and aqueous alcohol, but not in alcohol of '865, or stronger. It does not coagulate on boiling. When thoroughly dried it forms a gray powder, which does not admit of being perfectly redissolved in water. Acetic acid, tannin, and alum throw down precipitates, which are insoluble in an excess of the test. Ferrocyanide of potassium does not precipitate a solution of pure pyin ; but on the addition of a little hydrochloric acid, a precipitate appears, which immediately vanishes on the addition of a little more of the acid. Accord- ing to Mulder, it is identical with tritoxide of protein. Diagnosis of pyin. Pyin may be recognized by its reactions with acetic acid and alum. It may be distinguished from the pro- tein-compounds (albumen, fibrin, casein,) in the same manner as pepsin and glutin. It differs from pepsin, by its acetic- acid precipitate not re-dissolving in an excess of the test, and from glutin and chondrin, by a similar behaviour on the part of the alum precipitate. 9. Extractive Matter's. After the removal of the protein-compounds from the animal fluids, there still remain certain salts, (lactates, chlorides, phos- phates, and sulphates,) together with organic nitrogenous matter, which after evaporation remain as an amorphous mass. It is to this organic nitrogenous matter, after the salts have been re- moved by their appropriate solvents, that the term extractive matter is applied. It is as generally diffused over the whole system as the protein-compounds ; we meet with it in blood, bile, milk, urine, mucus, pus, and all the soft tissues, and most abiindantly in muscular flesh. Hence the extractive matter of flesh merits especial attention. The extractive matters from other sources, as from blood, urine, milk, &c., will be subse- quently noticed, and their leading characters contrasted with those of our standard extractive matter, the extract of flesh. EXTRACTIVE MATTERS. 31 For the purpose of tlioroiighly examining tlic extract of flesh iu all its chemical bearings, Simon experimented on eight pounds of the thickest part of a leg of pork, which he freed as much as possible from sinew, fat, cellular tissue, and CA'cry- thing; that was not absolutely muscular flesh. It was then cut in small pieces, and cold water was poured over it. After being allowed to stand in water for some time, it was removed and boiled three successive times in fresh water. These boilings were collected, and a little fat skimmed off". The cold water in which it was first placed, was then boiled and mixed with the rest. The whole was then filtered, and appeared as a light yellow fluid, with a strong smell and taste of broth. This fluid was evaporated to the consistence of a thin syrup. After cooling, it did not gelatinize, and contained no glutin, or at most, a mere trace. Alcohol was added to this thin syrup, until all the constituents insoluble in spirit, appeared to have separated, and deposited themselves at the bottom. "VVe thus separate the extractive matter into two distinct parts, one, soluble in water, but not in dilute alcohol, the other soluble in the latter menstruum. The former, when evaporated at a gentle temperature is of a brownish yellow coloiu", and is tolerably firm, tenacious, and tough ; it is termed water-extract. The latter must be evaporated to the consistence of an extract, and treated with from twelve to sixteen times its volume of absolute alcohol. The mixture must then be heated, and well shaken, so as to mix the alcohol with the deposited portion as thoroughly as possible. The alcoholic solution clears on standing, and assumes a yellow coloui-. It must be removed from the insoluble residue, and gently evaporated to a clear brown syrup, which after cooling and standing for some time assumes a solid form ; it dissolves freely both in water and absolute alcohol. By repeatedly treating the insoluble residue with hot absolute alcohol we remove all that is soluble in that fluid, and there is left a tolerably firm, tough, brown extract, which is soluble only in aqueous alcohol, and to which the term spirit -extract is given. We distinguish the portion which is soluble in absolute alcohol by the term alcohol- extract. 32 ORGANIC CONSTITUENTS. The extractive matter is tlms separated into tliree distinct p.arts : tliese are — A. That which is soluble in water, but not in dilute alcohol : water-extract. B. That which is soluble in water and spirit, but not in an- hydrous alcohol : spirit-extract. C. That which is soluble in water, in spirit, and in anhydrous alcohol : alcohol-extract. A. The water-extract contains : a. Constituents precipitahle by tannic acid : (a) A matter not precipitahle by neutral acetate of lead, but by basic acetate of lead and bichloride of mercury. {b) A matter precipitahle by neutral and basic acetates of lead, and by bichloride of mercury. j3. Constituents not precipitahle by tannic acid : (c) A gummy matter not precipitahle by neutral acetate of lead, or bichloride of mercur}'^, but by basic acetate of lead. (d) A matter freely precipitahle by basic acetate of lead, and very slightly by neutral acetate of lead, and bichloride of mercm"y. {e) A matter precipitahle by neutral and basic acetates of lead, but not by bichloride of mercury; the Zomidin of Berzelius. B. The spirit-extract contains : a. Constituents precipitahle by tannic acid : {a) A matter not precipitahle by neutral or basic acetate of lead, but by bichloride of mercury. (b) A matter not precipitahle by neutral acetate of lead, or bichloride of mercury, but by basic acetate of lead. (c) A matter precipitahle by nevitral and basic acetate of lead, but not by bichloride of mercury. f^. Constituents not precipitahle by tannic acid : {d) A matter rather indifferent toAvards reagents. (e) A matter discovered and described by Chevrcul ; Kreatin. EXTRACTIVE MATTERS. 33 C. The alcohol-extract contains : a. Co7istituenis pi'ecipitable by tannic acid: {a) A matter precipitable by basic acetate of lead^ and bichloride of mercury, but not by neutral acetate of lead. (Z*) A matter precipitable by basic acetate of lead, and by an excess of bichloride of mercury, but not by neutral acetate of lead : it is crj^stalline. j3. Constituents not precijntable by tannic acid : (c) A matter precipitable by basic acetate of lead, but not by neutral acetate of lead, or bichloride of mercury. The substances Aa, Kb, B«, &c., must be regarded as the proximate constituents of the three groups of extractive matters. We shall arrange them in two classes, according as they are or are not precipitable by tannin. Constituents of the extract of flesh, precipitable by tannin. Aa exists in very small quantity in the water-extract : it may be distinguished from the protein-compounds by its indifference towards ferrocyanide of potassium ; from pepsin and pyin, by its indifference to dilute acids ; and from chondi'in and glutin by its aqueous solution, not gelatinizing on cooling. Ab may be distinguished in the same manner as Aa, from the protein-compounds, pepsin, &c.i It differs from Aa in being precipitated by protochloride of tin. When isolated it is tolerably soluble in alcohol, although that fluid will not extract it directly from the water-extract. Ba occurs in minute quantity in the spirit-extract'. It may be distinguished from the preceding compounds by its solubility in spirit, and by its reaction with the acetates of lead. These three substances, Aa, Ab, and B«, differ so slightly in their reactions with various tests, that Ave may conclude that in all probability they are merely modifications of one and the same matter. ' The same observation applies equally to all the following constituents of extractive matter. 3 34 ORGANIC CONSTITUENTS. Bb may be clistingiiislied from the preceding compounds by its indifference towards bichloride of mercury. Be is freely precipitated by the addition of sulphate of copper, but the deposit which is of a brownish colom', readily dissolves in an excess of the test. If just a sufficient quantity of the solution of sulphate of copper to dissolve the precipitate be added, and heat applied, a green precipitate forms, and the supernatant fluid is likewise green. Alum, cautiously added, throws doAvn a brownish yellow flocculent precipitate, which dissolves in an excess of the test. Infusion of galls, added in small quantity scarcely produces any turbidity in a solution of this constituent, but when added freely, a copious precipitate is deposited, which disappears on the application of heat, but returns as the solution cools. Be may be distinguished from Aa, and Ab, by its indifference towards bichloride of mercury ; from Bff, and Bb, by its behaviour with neutral acetate of lead, and sulphate of copper. C« is precipitable by protochloride of tin. This, to- gether with the reactions it displays towards bichloride of mercury and infusion of galls, and its solubility in anhj-^drous alcohol, is sufficient to distinguish it from any of the preceding constituents. The characteristics already mentioned are sufficient to distinguish Cb. Constituents of the extract of flesh not precipitable by tannin. Ac is remarkable for its indifference towards reagents. The only important tests have been already mentioned. Ad is freely precipitated by bichloride of platinum ; moreover the precipitate thrown down by basic acetate of lead is increased by heat. Ae [zomidin) pelds a very copious green or grayish green deposit, on the addition of acetate of copper. This pre- cipitate does not dissolve in an excess of the test, but dissolves freely in acetic acid : on boiling this precipitate in caustic potash it is rendered brown, while the supernatant fluid assumes a faint purple red tint. Infusion of galls renders a solution of zomidin slightly turbid, and after some hours a few flocculi are deposited, possibly in consequence of the existence of some impurity in the zomidin. EXTRACTIVE MATTERS. 35 Berzelius considers that the savour of boiled and roasted meat depends on this constituent. Bd yields a yellow precipitate to bichloride of plati- num, a white deposit to the acetates of lead, and its solution is rendered slightly turbid by infusion of galls : the turbidity however disappears on the application of heat. Be [kreatin) is distinguished from all the preceding sub- stances by its property of separating in rectangular crystals, and by its indifference towards the ordinary reagents. Cc yields a copious white precipitate (which soon darkens) to nitrate of silver, and a chocolate-brown deposit to a solution of iodine. There can be no doubt from the recent investigations of Mulder, that the binoxide and tritoxide of protein occui' in the constituents of the water-extract, and are probably identical with some of them. The relative proportions of water-, spirit-, and alcohol- extract in flesh, blood, urine, and milk, appear to fluctuate. Simon found that, in the extractive matter of flesh, the water-extract predominates, while he could only obtain a very small amount of spirit -extract ; in the extractive matter of blood, the water- extract is also the most abundant, but here the amount of alcohol-extract is less than that of spirit-extract ; in the ex- tractive matter of urine, the water-extract was the most scanty, and the alcohol-extract the most abundant ; and in the ex- tractive matter of milk, the alcohol-extract was the least of the three. Extractive matter of blood. Simon gives the following du'ections for the exhibition of the extractive matter of blood. A quart of blood is heated to the boiling point, and a suflicient quantity of water is then added to reduce it to a thin pulta- ceous state. After standing for some time, it is strained, and the red fluid which passes through is again boiled. In this manner we obtain a clear yellow fluid, which no longer becomes turbid on the application of heat. On evaporation, this fluid assumes a dark green colour ; and on further concentration to the consistence of a syrup, it changes to a brown tint. At the same time a film forms on the surface, which leads to the con- clusion that a caseous matter (in this case globulin) is present. The extract exhibits an alkaline reaction. 3G ORGANIC CONSTITUENTS. Wlien tlie extract lias been reduced to the consistence of a syrnp, it is treated with alcohol of 833, which throAvs down a copious brown precipitate. The clear alcoholic fluid is removed and evaporated. It forms a browu extract^ which is devoid of the aromatic odour that is perceptible in the spirit-, and alcohol- extract of flesh. The residue is evaporated to the consistence of a thin extract, and then treated with absolute alcohol, which, when evaporated, leaves a very small amount of alcohol-extract. Water-exti'act of blood. It is of a dark brown colour, and possesses a strong taste of salt. Its reaction is slightly alkaline, and there is nothing remarkable about its odour. On incine- ration it leaves an alkaline ash, which effervesces on the addi- tion of an acid. The following are its most important chemical relations. Acetic acid produces a turbidity which only disappears in a great excess of the test : ferrocyanide of potassium throws down a slight precipitate from the clear acid fluid, consisting of albumen. Neutral and basic acetate of lead produce a copious brown precipitate ; bichloride of mercury, even in excess, produces no apparent change. Infusion of galls induces merely a slight turbidity. Spirit-extract of blood is of a dark brown colour, and a strongly salt taste. During evaporation it becomes covered with a coating of salts ; and, after a certain degree of concentration, it solidifies, in consequence of the amount of the salts. It leaves a porous coal, which does not very easily burn to a white ash. This ash is strongly alkaline, and effervesces briskly on the addition of an acid. The aqueous solution of the spirit-extract has a verj^ feeble alkaline reaction. Acetic acid produces a slight turbidity, which disappears on the addition of a considerable excess of the test. Neutral and basic acetates of lead and infusion of galls pro- duce copious precipitates ; bichloride of mercury effects no apparent change. Alcohol-extract of blood. When the alcohol in which this substance is contained is evaporated to the consistence of an extract, and then warmed with ether, w'c obtain a greenish brown matter, which, after the evaporation of the etlier, is EXTRACTIVE MATTERS. 37 soluble in water. Its amount is very minute ; it has a feeble, alkaline reaction, and possesses a very disagreeable and nau- seous taste. It is precipitated by perchloride of tin and nitrate of silver, but not by neutral or basic acetate of lead, bichloride of mercmy, or infusion of galls. Extractive matter' of urine. The urine must be evaporated in order to precipitate the salts as much as possible, and then placed in a freezing mixture for the same purpose. When it is reduced to the consistence of a thick syrup, alcohol of "SSS must be added to it as long as any additional precipitate is thrown down. This precipitate consists of salts, and contains hardly any extractive matter ; it must be separated from the supernatant fluid, washed with alcohol of -SSS, dissolved in water, and precipitated again by alcohol. In this manner the spii'ituous solution assumes a yelloAV colour, while the salts are rendered colourless. By the evaporation of this yellow spirituous solution we obtain the water-extract of urine. It exists in very minute quantity. Infusion of galls produces hardly any marked effect, neither does bichloride of mercury ; neutral and basic acetates of lead yield a copious precipi- tate. Spirit-extract of urine is obtained by evaporating the spirituous solution to the consistence of a thick extract; it is then treated with a little anhydrous alcohol, and subsequently with ether. By shaking, and the application of a gentle warmth, the ether assumes a yellow colour, and a light brown matter separates ; this must be washed in ether, and then treated with absolute alcohol, which throws down a brown extractive matter, while the alcohol assumes a nearly similar tint. This precipi- tate must be washed with absolute alcohol, dissolved in water, and evaporated. Its ash contains a considerable amount of chlorides. Infusion of galls, bichloride of mercury, and neutral acetate of lead do not affect its solution, but basic acetate of lead throws down a copious precipitate. Alcohol-extract of urine is obtained by the evaporation of the brown alcoholic solution referred to a few lines back. On the addition of anhydrous alcohol it is reduced to a yellow fluid, from which lu'ea separates on slow evaporation. After the removal of this substance, we have the substance known as alcohol-extract of urine. Infusion of galls, bichloride of mer- 38 ORGANIC CONSTITUENTS. cury, and neutral acetate of lead do not influence its solution; it is, however, precipitated by basic acetate of lead. Extractive matter of milk. For the purpose of investi- gating the properties of this substance, Simon evaporated a quart of "woman's milk (partly colostrum and partly during the early weeks of lactation) to about eight ounces, and he then removed the casein and butter by the addition of alcohol. After filtration, some water was added ; the fluid was again evapo- rated to a residue of a few ounces, treated with alcohol of "833, and allowed to rest for some time. Sugar of milk of a slightly yellow colour was deposited, and the supernatant fluid had nearly the same tint. The latter was evaporated on the water- bath to the consistence of a syrup, and then treated with anhydrous alcohol, which reduced nearly the whole syrup to a solid consistence, while the alcohol above it, which contained the alcohol- extract, was hardly tinged yellow. The precipitate which is thrown down by the anhydrous alcohol contains the spirit- extract, and the water-extract is contained in the yellow-coloured sugar of milk. The ivater-extract of milk is obtained by treating the pre- cipitated sugar of milk with water, and allowing it to stand, well covered, for some days. In this manner we obtain a yellow, almost clear, and viscid fluid, standing above the white sugar of milk. On removing this fluid, and allo^v^ng it to evaporate spontaneously, a fresh quantity of sugar of milk is deposited ; in fact, it appears impossible to remove all traces of this consti- tuent of the milk from the water-extract. Alcohol throws down a yellow, glutinous, tough extract, which exhibits a feeble alkaline reaction towards litmus paper. This is the water- extract. When burned, it leaves a porous coal, from which a white alkaline ash, containing carbonates, may be obtained without much difficulty. It is precipitated from its solution b}^ infusion of galls, basic and neutral acetates of lead, but not by bichloride of mercury. The spirit-extract of milk is obtained from the precipi- tate which was thrown down by the anhydrous alcohol; it must be dissolved in a little water, and treated with alcohol of •833, which usually causes the separation of a little sugar of milk. The spirituous solution must now be evaporated to a very small residue, and some distilled water added, which produces COLOURING MATTERS. 39 a considerable turbidity, aud ultimately causes a slight white precipitate. The nature of this precipitate remaiiis doubtful. The spirit-extract is thrown down from its solution by infusion of galls and basic and neutral acetates of lead, but not by bichloride of mercury. The alcohol-extract of milk is obtained by the evapora- tion of the yellow anhydrous alcoholic solution that has been already referred to. It exists in very minute qiiantity, is of a yellow colour, and is not materially affected by infusion of galls, basic or neutral acetates of lead, or bichloride of mercurj^ Ptyalin and pyin may be regarded as water-extracts of saliva and pus. 10. Colouring Matters. I. THE BLOOD. a. Haematin. This colouring matter is inclosed in thin sacs or vesicles, composed of a protein-compound, globulin : these vesicles exist in countless numbers in the circulating fluid, and are termed blood-corpuscles. It has been generally assumed that this pigment exists in two distinct chemical states in arterial and venous blood, ha\ing in the former an excess of oxygen, in the latter an excess of carbon or carbonic acid. Mulder has, however, shown that its ele- mentary composition is the same, whether obtained from arterial or from venous blood, and that it may be represented by the formula! C^^ H„, N^ O^ Fe. Its composition seems likewise to be identical in all vertebrated animals.- Various methods have been proposed for the exhibition of pure hsematin. The following, adopted by Simon, is perhaps the simplest. AMiipt and thoroughly dried blood must be pulverized, and its fat removed by repeated extraction with ether. It must then be boiled with anhydrous alcohol, and during the process of ebullition a quantity of sulphuric acid, di- luted with cold alcohol, must be added, sufficient to communicate ' See Appendix I, Note 16. - Lecanu examined bamatiu from hmnan blood, and from that of the ox, domestic hen, duck, frog, carp, and mackerel. The only thfference was in the proportion of peroxide of iron left when the hfcniatin was incinerated. 40 ORGANIC CONSTITUENTS. a marked acid taste to tlie mixture. In this manner a blackish brown solution of sulphate of hsematin is obtained, which must be saturated with carbonate of ammonia. If the mixture be allowed to stand for some time, the sulphate of ammonia may- be separated by filtration; the greater part of the alcohol must then be removed by distillation. This part of the process re- quires much caution, and the distillation must be conducted very gently, as the action of the fluid is often violent. The hsematin, which is ultimately precipitated, must be carefully washed with water, in order to remove any traces of sulphate of ammonia. It must then be dried on the water-bath, pulverized, and treated with ether as long as it continues to communicate a dark tint to that menstruum. The ether takes iip a certain amount of haemaphsein associated with fat. The hsematin must be boiled in distilled water, as long as it continues to give oft' salts and alcohol-extract, and then in alcohol, till everything soluble in that fluid is removed. The substance that is left may be regarded as pure hsematin. We can only isolate it in this coagulated and insoluble con- dition. In the blood-corpuscles it exists in a state of solution. When obtained by the process that we have just described, it is of a blackish brown colour, is devoid of taste and odoxrr, is insoluble in water, ether, fatty and ethereal oils, and in bi- sulphuret of carbon. It is usually stated to be insoluble in alcohol, but, according to Simon, boiling alcohol takes it up slightly. It is freely soluble in alcohol acidulated Avith sidphuric, hydrochloric, nitric, or acetic acid, and communicates a tint to that menstruum varying from a broAvn to a light red, according to the strength of the solution. On the addition of water the haematin gradually precipitates. Hsematin dissolves freely in water or alcohol rendered alkaline by ammonia, potash, or soda : but the alkaline reaction is not in any degree neutralized by the hsematin. On the application of a strong heat haematin swells up, gives oS" an animal odour, and burns Avitli a clear flame. It leaves a voluminous coal, which is ultimately reduced to a dark red ash. When heated in a test tube it develops ammonia, and gives origin to a reddish empyreumatic oil. Mulder has carefully examined the action of chlorine on hsematin. He found that if a cmrent of chlorine be transmitted through water containing hcematin in suspension, the iron leaves COLOURING MATTERS. 41 the other elements^ and forms a chloride of iron, while the atom of metal thus removed is replaced by six atoms of chlorous acid, and a compound is formed, which is represented by the formula C H„ N, 0, + 6 CI O . 44 'i'J 3 3 During this process the red colouring matter is destroyed, and the new compound appears as a white flocculent precipitate. It must not, however, be assumed from this experiment that the red colour* of the blood is dependent on the iron, for that con- stituent may be removed from the hsematin without materially aflFecting its tint, as may be shown in the following manner. Let some dried blood be mixed with concentrated sulphuric acid, and after standing for some days let water be added. Hydrogen gas is evolved by the action of the acid on the dried blood, and sulphate of the protoxide of iron is formed. If the blood, after this process, be carefully washed, a mixture of alcohol and sulphuric acid will extract from it red hsematin in combination with sulphoproteic acid, but perfectly free from iron. A an Goudoever has deduced the following formula for this compound : Cg^ H37 Ng Ojj) S03=C^^ H22 Ng Og (the organic part of hsmatin,) "l-C^p Hjj Nj 0,2, SO3 (sulphoproteic acid,) +4 HO. Although this experiment affords conclusive evidence that the red colour of the hsematin is not dependent on the iron, yet this metal is very firmly combined with the four organic elements of this constituent. Well prepared hsematin may be submitted for several days to the action of dilute hydrochloric or sulphuric acid, A^ithout the iron diminishing in the slightest degree. Ha^matin treated in this manner, left after incineration 9'49g of peroxide of iron,' the amount that is always yielded by well-purified haematin. Peroxide Metallic of Iron. Iron. ' 111 100 parts of haematin from human blood, Lecanu found . lO'OO = 6'93 „ from blood of ox „ „ . 12-85 — 8-90 „ from arterial blood of ox, Mulder found, 9*60 = 6"66 „ from venous blood of ox „ „ . 9'82 = 6-75 „ from blood of ox, Simon found . 11"50 = 7'97 „ from blood of sheep, Mulder found . 9'30 =i 6"45 42 ORGANIC CONSTITUENTS. The condition in which the iron exists in hsematin (whether as an oxide^i a carbonate, a carburet, or in the metallic state) has long been dispiited. The probability of its existence in a metallic state is strongly supported by the evolution of hydrogen that occurs when the clot is digested in sulphuric acid, and water is added ; and Mulder suggests that this metal probably exists as an integral constituent of hsematin, in just the same manner as iodine occurs in sponge, sulphur in cystin, or arsenic in the kakodyl series. Numerous attempts have been made with the view to ascer- tain the proportions in which hsematin and globulin combine, but the results have been very discordant. According to Berzelius, the hsematoglobulin of human blood contains 100 parts of globidin, and 5*8 of hsematin. Simon found the ratio to be 100 of globulin to 6*5 of hsematin in the blood of a healthy young man, and 100 of globulin to 5-3 of hsematin in the healthy blood of a stout girl. In disease, the variations are much greater. Simon has found as the limits 8*5 and 3"3 of hsematin, corresponding to 100 of globidin. Regarding the origin of hsematin, it must clearly be generated in the organism, since it does not exist in the vegetable kingdom. Mulder conceives that it is generated from the normal constituents of the blood in the course of the circulation. Its destination also is obscure. In common with all the constituents of the body, it must be generated, consumed, and reproduced ; but in respect to the actual metamorphoses that it undergoes in the organism, or their object, we are perfectly in the dark. Mulder suggests that the products of the decomposition of hsematin may possibly be traced to the bilifulvin of the bile. Diaynosis. Haimatin may be known, both in its coagulated and soluble state, by its colour. When combined with globuhn, in the blood-corpuscles, it may be recognized by the microscope. In its coagulated state it may be recognized by its insolubility in water, alcohol, and ether. b. HcBmapheein. This term is applied by Simon to the brown colouring matter which seems to be associated with hsematin in ' Iron is not separated from hsematin by ammonia, potash, or soda ; nor is its pre- sence indicated by tannin or ferrocyanide of i)otassiuin, reagents which are so capable of detecting the presence of oxide of iron in ordinary cases. COLOURING MATTERS. 43 the blood of the vertebrata, and is apparently identical, or nearly so, with the yellow colouring matter described by Sanson.' It may be distinguished by its solubility in water, alcohol, and ether, and by the intense brown-red colour that it com- municates to its alcoholic solution. When exposed to heat on a platinum spatula, it does not melt, but develops ammoniacal vapours, burns with a clear flame, and leaves a very trifling ash, which is perfectly free from peroxide of iron. Marchand remarks that hsemaphsein is nothing more than hsematin modified by an alkali, just as O'Shaughnessy's subruhrin, and Golding Bird and Brett^s cJilorohamathi and wmithoheematin are products of the action of nitric acid on hsematin.- c. Hcemacyanin, or a blue colouring matter, has been detected by Sanson in healthy blood, by Lassaigne and Lecanu in the blood of icteric patients, and by Chevreul in the bile. Simon never succeeded in detecting it. For the method of isolating it, and for a description of its chemical characters we must refer to Sanson's paper. It is sufficient to remark that it is described as being insoluble in water, alcohol, and ether, but shghtly soluble in boiling alcohol, from which, however, it separates on cooling. On the addition of ammonia to its alcoholic solution, a green colour is evolved, but on the addition of an acid, the blue colour is restored. It contains no iron. II. THE BILE. a. The most important colouring matter of the bile is that to which it owes its characteristic brownish yellow tint. It is termed cholepyrrhin by Berzelius, and bilqihrnn by Simon. We shall adopt the latter term. On the gradual addition of nitric acid to a fluid that contains this substance in solution, a very characteristic series of tints are evolved. The fluid becomes first blue, then green, afterwards violet, and red, and ultimately assumes a yellow or yellowish brown colour. • Journal de Pharmacie, Aout 1835, p. 420. - The discoveiy of the true nature of subruhrin is due to Drs. Brett and Golding Bird, who showed that it is merely hsematin mixed with a little allramen. Their chlorohjematiu is haematin partly oxidised by nitric acid, as Marchand observes ; and their xanthohsmatin is at present supposed by Dr. G. Bird to be identical with some of the products of the oxidation of protein recently described by Mulder. 44 ORGANIC CONSTITUENTS. All attempts to isolate this substance from tlie bile, by cbemical means, have failed; it is apparently decomposed by the processes that are adopted in the analysis of this compli- cated fluid. We sometimes, hoAvever, find it deposited in the form of a yellow powder, in the gall-bladder, or concreted, with a little mucus, constituting a biliary calculus. In this manner we have an opportunity of examining its che- mical reactions. Biliplijein is of a bright reddish-yellow colour, and is only slightly soluble in most fluids ; it is devoid of taste and odour, and yields ammonia on dry distillation. Water takes up an extremely minute trace of biliphaein, just sufficient to communicate a faint yellow tinge. Alcohol dissolves more than water, but only a very inconsiderable quantity. Its best solvent is a solution of caustic potash or soda, both of which are more efficient than ammonia. On exposing this solution to the atmosphere, oxygen is absorbed, and the yellow colour becomes gradually green. On the addition of an acid to this yellow or green solution, there is a precipitation of green flocculi which possess all the properties of chlorophyll, or the green colouring matter of leaves. In this state it is termed biliverdin by Berzelius. It is no longer biliphaein (or cholepyrrin), but a product of its metamorjihosis. The colouring matter of the bile may be separated from a composite animal fluid, by evaporation to dryness; by successive extractions with alcohol of '845, ether, and water; by dissolving the colouring matter in a solution of potash, and then precipi- tating it, as biliverdin, by hydrochloric acid. Diagnosis. The action of nitric acid afi'ords a certain test of the presence of biliphsein. h. After the separation of the biliphaein, by conversion into bihverdin, another colouring matter remains, to which Berzelius has given the name of bilifulvin. It is a double salt of lime aud soda, combined with an organic nitrogenous acid, to which the term bilifulvic acid has been applied. When isolated, this acid is insoluble in water and in alcohol, and separates in pale yellow floccuH when it is precipitated from an aqueous solution of its salts by a stronger acid. Whether bilifulvin is an actual constituent of the bile, or whether it is a mere product of meta- morphosis, is unknown. COLOURING MATTERS. 45 III. THE URINE. a. Uroerthyrin. In certain pathological conditions (espe- cially in intermittent fevers) the urine possesses an intensely- red colour, and deposits a dark red precipitate. Proust, who was the first that carefully examined this class of sediments, discovered in them a peculiar acid^ to which he gave the name of rosacic acid. He subsequently found that this acid was merely a compound of uric acid with a red colouring matter. This red colouring matter has been observed by Landered in the sweat from the axillary region of a girl with fever. In order to isolate this pigment, we must boil a sediment of this nature in spirit, which will take up the colouring matter and a little uric acid. This uric acid must be removed by con- centration and cooling, and then b}^ evaporation to dryness, we obtain uroerythrin. It yields a vividly scarlet powder, is devoid of odour, possesses but little taste, and is tolerably soluble in water and spirit : these solutions are faintly acid. b. The blue and black pigments that have been described by various authors (Braconuot,i Spangenberg,^ Granier and Delens,^ Marcet, Prout,"* &c.) and have received the names of cyanurin and melamiynn, are not of sufficient importance to require any observations. 11. Billn. Bilin is the name given by Berzelius to the substance which he considers as the principal and most important constituent of the bile. The following is the most simple process for its exhibition :^ Acidulate perfectly fresh filtered ox-gall with a few drops of acetic acid, and precipitate it with neutral acetate of lead. The bilifellinic acid, which still remains in solution, must then be precipitated, as a plastery mass, by basic acetate of lead, and the filtered or decanted Kquid, in which there is usually a little • Ann. de Chem. et de Phys. t. xxix, p. 252. ^ Schweigger's Journal, t. xlvii, p. 487. 3 lb. t. xxiii, p. 262. ■* Medico-Chirurgical Transactions of London, v. xii. ^ Lehraann, Lehrbuch der Physiologischen Chcmie, t. i, p. 309. 46 ORGANIC CONSTITUENTS. bilifulvin, must be decomposed by an excess of carbonate of soda. The precipitate is then to be extracted with absolute alcohol, and the soda carefully precipitated from this solution by dilute sulphuric acid. On evaporating the alcoholic solu- tion to dryness, we obtain bilin. The composition of bilin is not accurately determined. It is easy to show that it contains nitrogen, by heating it with an alkali, in which case it develops ammonia. Lehmaun always found traces of sulphur in it. Bilin forms a gummy, pale yellow mass, which when quickly dried and pulverized, yields a white powder, devoid of odour and possessing a singular sweetish-bitter taste, most perceptible at the base of the tongue and on the posterior fauces. Berzelius suggests that the sweetness may be owing to the admixture of a httle glycerin.^ It is freely soluble in water and in alcohol, but not in ether ; in fact it may be precipitated by ether from its alcoholic solution. When recently prepared, it is perfectly neutral. Heated to 212°, it begins to swell; at a higher tem- perature it becomes brown, develops a peculiar odonr, and when inflamed, burns with a bright clear flame, leaving a porous ash. An aqueous solution of bilin is not affected by acids, nor by earthy or metallic salts ; neither does chlorine seem to induce any peculiar change. A concentrated solution of potash sepa- rates an oleaginous tough mass, (a compound of bilin and potash,) which is soluble in water and in alcohol, Bilin is remarkable for the facility with which it undergoes metamorphoses. An aqueous or alcoholic solution in vacuo soon assumes an acid reaction. Its decomposition is accelerated by warmth, by the presence of organic matters, as mucus, &c., and more especially by the action of the mineral acids. Metamorphoses of Bilin. Bilin and hydrochloric acid. On digesting bilin with dilute hydrochloric acid, five distinct sub- stances are ultimately obtained, three of which are insoluble in water, and have received from Berzelius the names oi fellinic acid, cholinic acid, and dyslysin ; the remaining two being ' As the bile contains oleate, margarate, and steavate of soda, there is no difficulty in accounting for the presence of glycerin. BILIN. 47 soluble in water, viz. taurin and hydrochlorate of ammonia. — The evaporation of an aqueous solution of the above mix- ture leaves as a residue a crystalline mass of taurin and hydro- chlorate of ammonia; the latter may be removed by alcohol of •838, and the taurin may then be recrystallized from a solution in hot water. Taurin forms colourless regular six-sided prisms, terminated by fom'- or six-sided pp'amids. It is hard, cramiches between the teeth, has a cooling taste, but is neither bitter nor salt, dis- solves in about sixteen times its Aveight of water at 60", and is more soluble at a higher temperatm'e. It is veiy slightly solu- ble in alcohol. It is dissolved without decomposition in con- centrated sulphuric and nitric acids, and gives no reaction with the ordinary reagents. Its composition is represented by the formula C^ N H„ Oj^^. Hence, as Lowig remarks, it may be regarded as a combination of binoxalate of ammonia and water, for C, N H. O,, = 2 C^ O3 + N H3 + 4 HO. On treating the resinous mass, which is insoluble in water, with alcohol, dyslysin is left, and the two acids are dissolved. Dyslysin dissolves with some difficulty in boiling alcohol, and falls again on cooling as an earthy powder. It has not been further investigated. Cholinic and fellinic acids are associated in the alcoholic solution. In many respects they closely resemble each other : they are almost insoluble in water, they dissolve in all propor- tions in alcohol, and they form nearly similar compounds with the alkalies, earths, and metallic oxides. Their salts of am- monia and baryta, however, differ in several respects, and by means of these reagents we can isolate the acids. If we evapo- rate a solution of their ammoniacal salts, cholinate of ammonia separates as a white soapy mass, while fellinate of ammonia remains in solution, and appears after due evaporation as a soft, greasy, yellowish substance. When an aqueous solution of cholinate of ammonia is decom- posed by hydrochloric acid, cholinic acid separates in light white flocculi, which after drying form a brown pulverizable mass. It is only slightly soluble in ether. The cholinate of baryta is almost insoluble in alcohol. Fellinic acid may be exhibited in a similar manner. It sepa- rates from its solution in snow-white flocks, and after drying 48 ORGANIC CONSTITUENTS. forms a white, eartliy, inodorous and bitter mass, wliicli fuses at 212° without decomposition. In boiling water it undergoes fusion, and dissolves to a small extent ; in this respect it differs from cholinic acid, which fuses but is wholly insoluble in hot water. It is soluble in ether, and its baryta salt dissolves freely in alcohol. Fellinic and cholinic acids possess the propert}^ of combining and forming acid compounds with undecomposed bilin, to which Berzelius has given the names of bilifellinic and bilicho- linic acids. Bilifellinic acid apparently exists as such in fresh bile : it may be obtained either from bile after the removal of mucus, colom'ing matters, and other acids, by neutral acetate of lead, or from pure bilin. In either case we add a solution of basic acetate of lead, which throws down a flocculent precipitate which soon collects into a soft, tenacious, plastery mass. The salt of lead must be decomposed by carbonate of soda, and the soda-salt in its turn, by sulphui'ic acid : we thus obtain a very soft, almost oily, yellow mass, from which the free sulphuric acid must be removed by carbonate of lead, and free fellinic and cholinic acids, by ether. We then obtain bilifellinic acid in the form of a thick sjTupy fluid soluble in every proportion of water, and possessing a bitter taste. If this acid be digested with oxide of lead, or decomposed by basic acetate of lead, a plastery bilifellinate of lead is again precipitated, while at the same time pure bilin is found in the supernatant fluid. Hence it appears that bilin combines with fellinic acid in more than one proportion. Bilichollnic acid appears to resemble bilifellinic acid in almost every respect. A mixture of these two bilin-containing acids constitutes Demaryay^s chohic acid,'^ and forms the principal part of Thenard's biliary resin. (Berzelius.) On cooling bilin in a solution of caustic potash till ammonia ceases to be developed, avc obtain, on evaporation, a clotty matter, Avliich, when dissolved in water and treated with acetic acid, precipitates a peculiar acid, the cholic acid of Gmelin. It forms fine silky acicular crystals, of which the taste ' Tliis substance is described in the chapter on the Bile. UREA. 49 is at once sharp and sweet. It is slightly soluble in cold, but more so in hot water ; it dissolves readily in alcohol : its solution reddens litmus. Most of the cholates are soluble, and possess a sweetish taste. Dumas assigns to this acid the formulai C , H,, 0„. 43 36 10 There is no subject in the whole domain of animal chemistrj'^ that is more perplexing and intricate than the bile and its constituents. In the preceding pages we have adopted the views of Berzelius, but upon this point (cholic acid) he is very undecided. In the edition of his ' Animal Chemistry/ pub- lished in 1840, he states that he conceives it probable that cholic acid is produced by bilin alone, and that any fellinic or cholinic acids that may be simultaneously present take no part in the metamorphosis. In his article ' Bile, ' in Wagner's ' Handworterbuch,' published two years later, he states that bilin in a state of purity undergoes only a very slight change by boiling with hydrated potash, and that he could not convert it into cholic acid in that manner. Cholic acid certainly does not pre-exist in the bile. Diagnosis of hilin. Bilin may be detected by its peculiar taste. It is distinguished from the previous substances by its solubility in water and absolute alcohol, and by its insolubility in ether. Although absolutely pure bilin is said by Berzelius to be unaffected by metallic salts, basic acetate of lead and per- chloride of iron throw doAvn white precipitates from an aqueous solution; the latter, on the application of warmth, assumes a cinnamon tint : these reactions are probably owing to the presence of bilifellinic acid. 12. Urea. Urea forms the -principal constituent of the solid residue of normal human urine. It is found in considerable quantity in the blood after extirpation of the kidneys, also in certain pathological conditions in which the renal functions are not properly discharged, as in diabetes, cholera, ischuria, and Bright's disease. That it does exist in healthy blood as a constant, although verij minute constituent, has also been recently proved by Marchand and Simon. Rees has detected ' See Appendix 1, Note 17. 50 ORGANIC CONSTITUENTS. it in the liquor amnii and in milk ; Kiilm and Lelimann in bile and biliary concretions ; Golding Bird in sweat ; Wright in saliva, Maclagan in the serous effusion into the ventricles in cer- tain forms of fever ; and various chemists in dropsical fluids, &c. Urea may be obtained from urine in a state of purity by any of the following methods. a. The nrine must be evaporated to the consistence of a syrup, and mixed when quite cold, with an equal volume of pure nitric acid of specific gravity 1"42. If the evaporation has been carried sufficiently far, the whole will form a thick crystalline mass, consisting of a compound of nitric acid and urea, which is sparingly soluble in nitric acid. All increase of temperature must be carefully avoided lest the nitric acid with the aid of heat, acting on the chlorides in the urine, should develop chlorine and nitrous acid, both of which, as we shall presently show, act powerfully in destroying urea. The impure crystals of nitrate of urea are to be carefully washed in dilute nitric acid, strongly pressed between folds of blotting paper, dried on a porous tile, redissolved in warm water, and neu- tralized with carbonate of lead. The residue after evaporation, must be treated with alcohol. In this manner we obtain an alcoholic solution of m-ea, from which sulphuretted hydrogen, and animal charcoal, will suffice to remove any traces of lead and colouring matter ; after due evaporation it will yield crystals of nearly pure urea. b. O. Henry mixes the urine with basic acetate of lead, and then adds sufficient sulpluu'ic acid to convert all the acetates into sulphates. After filtration through animal charcoal the fluid will yield on evaporation crystals of nearly pure urea. c. Berzelius recommends that the alcohol-extract of urine should be dissolved in water, treated with animal charcoal, filtered, and warmed to about 120", and that then as much oxalic acid should be added as the warm fluid will dissolve. Crystals form of sparingly soluble oxalate of urea, which must be dissolved, filtered through animal charcoal, recrystallized, and decomposed by carbonate of lime. Urea may also be obtained artificially by the decomposition of certain cyanates. The following is the best method for obtaining it in this manner on a large scale. Twenty-eight parts of ferrocyanide of potassium, and 14 of peroxide of UREA. 51 manganese^ are to be thoroughly mixed, and heated on an iron plate to a dull red heat. Tlie mixture smoulders into a brown mass which contains cyanate of potash, carbonate of potash, and sesquioxide of manganese. When cold it is to be repeatedly digested in cold water, and the solution mixed with 20' 5 parts of crystallized sulphate of ammonia dissolved in water. Sulphate of potash and cyanate of ammonia are formed ; and this latter substance, on the application of a slight heat, is converted into urea. Sulphate of potash usually separates at once, in crystals ; but, without stopping to remove them, we may evaporate the fluid on the water- bath to dryness, and remove the urea by a small quantity of water. On evaporating this aqueous solution to dryness, the urea may be extracted with boihng alcohol of 80 or 905, whilst the sulphate of potash remains undissolved. The alcohol is allowed to evaporate, and the urea separates from it in crystals. In this manner a pound of ferrocyanide of potassium will furnish one third of a poimd of pure urea. The composition of urea is represented by the formula^ C^^ H^ N,, O.^. It contains a larger proportion of nitrogen (46-728J5) than any other organic compound. Urea when pure and in crj^stals is Avhite and transparent : when deposited from a concentrated hot solution it is in the form of fine silky needles, but by very slow or spontaneous eva- poration it separates in colourless flattened four-sided prisms of specific gravity 1-35. It is soluble in its own weight of cold, and in every proportion of hot water ; in 4*5 parts of cold, and in 3 parts of boiling alcohol; it is slightly soluble in ether, about 1 part in 60, at a temperature of 63''. It deliquesces in a very moist atmosphere only, and even then its chemical properties remain unchanged. In dry air it is per- fectly permanent. It fuses at 250° into a colourless liquid, and is decomposed by a higher temperature into ammonia, cyanate of ammonia, and dry solid cyanuric acid. A concentrated watery solution may be boiled and preserved for a long time without any change, but if albumen, glutiu, mucus, or especially ferment, should be present, it is speedily converted into carbonate of ammonia. The possibility of this transformation is obvious from the formula C^ H^ N, 0„ (urea) +2 HO = 2 (CO,, NHJ. ' See Appendix I, Note 18. 52 ORGANIC CONSTITUENTS. With most concentrated acids it gives crystalline salts, espe- cially with nitric and oxalic acids. It is not precipitated from its aqueous solution by metallic salts, ferrocyanide of potassium, or tannic acid. "With hyponitrous acid it is instantly decom- posed into nitrogen and carbonic acid gases, which are evolved in equal volumes ; with chlorine it forms hydrochloric acid, ni- trogen, and carbonic acid. These decompositions are rendered ob\ious by the formulae C, II, N, Oj + 2 NO3 3=4 N 4- 2 CO, + 4 HO C, H, N2 Oj + 2II0 -1- 6C1=2N -|- 200^ -{- 6HC1. Compounds of urea. Nitrate of TU'ca is obtained by the direct addition of nitric acid in excess, to a concentrated solu- tion of urea. Its formula is C,^ H^ N„ 0,^-FNO^ + HO. It most commonly crystallizes in large colourless leaves, but some- times in small solid prisms. It dissolves in eight parts of cold, but more freely in hot water. It is sparingly soluble in nitric acid, with which it may be boiled without decomposition. This salt effloresces with great rapidity. ^ 100 parts of nitrate of urea correspond to 48-9 1-5 of urea. (Regnault and Percy.) Oxalate of urea is obtained by the mixture of concen- trated hot solutions of urea and oxalic acid. Its formula is C„ H^ N„0,, + C„ O, + H0. It crystallizes in long slender plates or prisms, as the fluid cools, since it is much less soluble in cold than in hot water. At a temperature of Gl° water dissolves only 4*37|^, and alcohol I'&l, of the oxalate of urea. Oxalic acid displaces nitric acid from its combination with urea. 100 parts of oxalate of urea correspond to 62*564 of urea. (Berzelius.) Sulphate of urea may be obtained by the double decomposition of oxalate of urea and sulphate of lime. ' Nitrate of urea, when heated to about 316°, decomposes, and disengages a con- siderable quantity of carbonic acid and nitrous oxide, in the exact proportion of two volumes of the first to one of the latter; the residue consists of free urea and of nitrate of ammonia. Nitrate of ammonia and urea crystallize successively out of an aqueous solution of the residue. These changes are shown by the formida 4 (Cj H, Ng O2, NO,,, IIO) = 4 CO + 2 NO + 2 (C^ H, Nj Oj-f-S (NH3, NO5, HO). The nitrate of ammonia subsequently changes into water and nitrons oxide, and the urea into carbonic acid and ammonin. During the decomposition of tlie nitrate of urea a new acid is formed in extremely minute quantities. It crystallizes in grayish white brilliant lamellae, reddens litmus paper, and is very slightly soluble in water, which allows of its being separated from urea and nitrate of ammonia. Pelouze has assigned it the formula C.^ H3 Nj O4. URIC ACID. 53 Hydrochlorate of urea has been formed by the direct combi- nation of dry urea with hydrochloric acid gas. It is a very unstable compound, and when exposed to the air dissolves into a very acid liquid^ from which hydrochloric acid is disengaged. Lactate, liippurate, and urate of urea have been described by Cap and Henry ; who in fact assert that in human urine the urea exists as a lactate. Pelouze has, however, disproved the existence of all these compounds. Prout has examined certain compounds of silver and lead, in which the urea seems to combine with the oxides of those metals as bases. They are of no importance in a practical point of ^dew. The presence of urea modifies the solubility and crystalline form of certain salts ; it causes common salt to crystallize in octohedra, instead of in cubes ; but it has been observed that if these octohedra are dissolved in pure water they recrystallize in cubes. This peculiarity affords a common microscopic test for the presence of urea. Diagnosis of urea. Urea is distinguished by its solubility in water and in alcohol, and by its behaviour with nitric and oxalic acids. 13. Uric acid. Uric acid is a constituent of the imnary secretion in appa- rently all classes of animals ; it is found in man and the car- nivora, in graminivora (Fownes),' in birds, amphibia, serpents, insects, and mollusca. It is the most common ingredient (in combination with a base) of imnary calculi and gouty concre- tions; it has been detected in the saliva (Wright), in sweat (Wolf),^ and on the surface of ulcers in arthritic persons (Schonlein.) Uric acid may be obtained in a state of purity, by the fol- lowing process, from the excrement of the boa constrictor,3 ' London and Edinburgh Phil. Mag. xxi, p. 139. "^ Dissertatio sist. casiim Calculositatis ; Tubing. 1817. ■* The excrements of the boa constrictor have been found by Prout to jdeld more than 90g of uric acid. (Annals of Philosophy, t. v, p. 413.) The excrements of the rattlesnake have been examined by Simon. He found in 100 parts of the diied residue — free uric acid, with a Uttle fat and extractive matters, 56-4 ; urate of am- monia, 31-1 ; urate of soda, with some chloride of sodium, 9-8 ; lu-ate of Ume, 1-4 ; phosphate of lime, 1-3. Although we have retained the term "excrements" in ac- cordance with popular usage, the substance is in reality the urine of the serpent. 54 ORGANIC CONSTITUENTS. which contains a very large proportion of uric acid and urate of ammonia. To powdered boa constrictor's excrement add an equivalent proportion, or shght excess, of caustic potash. (We assume that the excrement is entirely urate of ammonia in this calculation.) Boil in water (in the proportion of lib. of ex- crement to 2 quarts of water) till the mass is reduced to dif- fused gelatinous fiocculeSj which speedily settle, lea\dng a dark- brown supernatant fluid. E,emove this fluid by decantation or filtration, and wash the urate of potash, which is collected, with cold water. It must then be heated in water, and more cavistic potash must be added, till the solution becomes clear. While still hot it must be poured into dilute hydrochloric acid, and allowed to stand. In this manner pure crystals of uric acid will be obtained.^ The slight excess of caustic potash used in the first instance seems to keep the colouring matter in solution. Uric acid is represented by the empirical formula^ C^ H„ N„ O^, or C,„ H^ N^ 0„ or C,„ H^" N^ O,; it is highly probable that it contains one atom of water in this state, and may be consi- dered as a hydrate, C, NH, 0+HO. Uric acid crystallizes in fine scales of a brilliant white colour and silky lustre, is tasteless, inodorous, heavier than water, almost insoluble in cold, and very slightly soluble in boiling water.^ It is insoluble in alcohol and ether. It dissolves in dilute nitric acid, with the evolution of equal volumes of car- bonic acid and nitrogen : on evaporating the solution a pink tint is produced, which, on the addition of ammonia in excess, changes to a purple-red coloui'. This is a characteristic test of the presence of uric acid. Boiled with peroxide of lead in water it is decomposed into oxalic acid and allantoin, and lu'ea is separated. Several of the compounds of uric acid, with the alkalies and alkaline earths, are of practical importance. Urate of potash is a frequent constituent of urinary calculi : it may be obtained by boiling urate of ammonia with potash. On cooling, the urate of potash yields a mass of very minute aci- ' The various forms under which lu-ic acid crystallizes are noticed under the head of Urinafy sediments. ' Sec Appendix I, Note 19. ^ According to Liebig, uric acid requires 15,000 parts of cold, and 1,932 parts of boihng water, for its perfect solution. It dissolves in all alkaline fluids, in solution of phosphate of soda and of liorax, hut not in solutions of the bicarbonates of potash or of ammonia. URIC ACID. 55 cular crystals, or else separates in granules or scales. It dissolves in 140 parts of cold, and in 85 parts of boiling water. Urate of soda may be obtained in a similar manner, or by boiling uric acid in a solution of borax. It is far less soluble than the former salt ; one part of it requiring for its solution 372 parts of cold, and 124 parts of boiling water. In other respects it closely resembles it. It occasionally constitutes a very peculiar stellar form of deposit in the urine. Liebig has shown that uric acid dissolves Avitli great facihty in a solution of common phosphate of soda, that the fluid from being al- kaline becomes acid, and that there are formed a urate of soda, and an acid phosphate of soda. It is in this condition that he supposes uric acid to exist in the urine. Urate of ammonia, in a state of purity, invariably crystallizes in needles, but if a httle chloride of sodium be added to its so- lution we no longer obtain, on evaporation, a crystalline acicular deposit, but the peculiar amorphous form in which ui*ate of am- monia occurs in urine. On the addition of chloride of sodium to water, in the proportion of 2' 59 to 1000, the solubility of urate of ammonia is increased in the proportion of 1000 to 450, or is more than doubled. (Dr. Bence Jones, in Trans, of the Medico-chirm-gical Societj^, 1844.) According to Liebig, this salt requires for its solution 1727 parts of cold, and 243 parts of boiling water. Urate of magnesia may be obtained by the addition of sul- phate of magnesia to a boihng saturated solution of m'ate of potash. On cooling, and after the fluid has been allowed to stand for some time, m'ate of magnesia is deposited in fine needles of a silky lustre, and arrayed in stellar groups. At 212° these crystals lose 5 atoms of water. Urate of magnesia dissolves in 3593 parts of cold, and 263 parts of boiling water. Urate of lime forms white glittering needles or leaves, which dissolve pretty readily in hot water, but are thrown down again on cooling. Diagnosis of uric acid. Uric acid is distinguished by the form of its crystals under the microscope, by its insolubility in water and in alcohol, and by its behaviour toAvards nitric acid and ammonia. The Metamorphoses of Uric Acid. Allantoin. One part of uric acid is boiled in 20 parts of Avater, and freshly prepared 56 ORGANIC CONSTITUENTS. peroxide of lead is gradually added to the boiling liquid, as long as its colour is observed to change. The hot liquid is then filtered and evaporated till crystals begin to form on its surface ; on cooling they form in considerable quantity, and constitute allantoin or allantoic acid, while urea remains in the mother liquid, and oxalate of lead on the filter. The following symbolical representation may elucidate this decomposition. 1 At. Uric acid . C,o H^ N^ 0^ 2 At. Peroxide of lead 0^ Pb., 7 At. Water . H, 0, C,„ H„ N, O,, Plu 1 At. AUautoiu . C^ H3 N^ O3 1 At. Urea . Cj H^ N^ Oj 2 At. Hydrated ox- alate of lead' C^ H^ O,.^ Pb^ C,„ H,i N, 0„ Pb, It is on this reaction that Liebig founds his theory of uric acid. He considers it to contain ready-formed urea and a hy- pothetical substance, for which he proposes the term uril JTi, or cyan-oxalic acid.^ For 1 At. Uric acid (Ci^ H, N, Og)— 1 At. Urea (C,, H, N, 0,) = 2 (C^ NO.,) =2 UT. Hence the rational formula for uric acid appears to be — - 1 At. Uric acid (C,o H^ N^ Og) = 2 ul -j- 1 At. Urea (C^ H^ N^ 0^). In the production of allantoin from uric acid, the urea is supposed to be set free, whilst the uril combines with oxygen and water in order to form oxalic acid and allantoin. The change may be illustrated in the following manner : 201 = C, N.^0^ = C^O^ + C^N.^. By the addition of 2 at. oxygen to the former term, C^ O^, we obtain 2C, O3 (oxalic acid), and by the addition of 3 at. water to the latter, C^ N„, we obtain C^ H3 N^ O3 (allantoin.) This substance allantoin, or as it is frequently termed allantoic acid, occurs ready formed in the allantoic fluid of the calf, from which it crystallizes spontaneously on cooling, when the fluid has been evaporated to one fourth of its volume. It then re- quires to be purified by recrystallization. The crystals are colourless and transparent, tasteless and ' 2 At. Hydrated oxalate of lead = 2 (Pb 0, C, O3, 2 HO) = C, II, 0„Pb2 '^ This name is suggested by its constitution ; for 1 at. Uril = C, NO^ = Cj O2, Cy, a formula that represents oxalic acid in ^^■hich an equivalent of oxygen is replaced by one of cyanogen. ALLOXAN. 57 inodorous, and exert no action on vegetable colours. They are usually prisms of the right rhomboid system, have a glassy lustre, and at 68" are soluble in 160 times their weight of cold, but in a much less quantity of hot water : they dissolve in hot alco- hol, but recrystallize as it cools. At a high temperature allan- toin is converted by the caustic alkalies, and also by most concen- trated acids (with the exception of nitric acid) into ammonia and oxalic acid. This change may be illustrated by the formula 1 At. AUantoin . • C^ H3 N., O3 3 At. Water ... H, O, C, Ilg N., Oe 2 At. Oxalic acid . . C^ O5 2 At. Ammonia . . Hg N2 C, Hg N, Ofi If we compare the composition of allantoin with that of uric acid and urea, we find that these substances bear a highly inte- resting relation to each other ; if we add to one atom of uric acid, one atom of urea, and one atom of water, we obtain a formula exactly corresponding with that of allantoin. 1 At. Uric acid . . Ci„ 11^ N^ Og 1 At. Urea . . . C, H^ N. 0^ 1 At. Water . . HO C.,H3N6 0g = 3(C,H,N,0,) i. e. = 3 At. AUantoiu. " According to this," as Liebig observes, " it is evident that the product of the secretion of the non-respiring foetus of the cow is, in a certain sense, identical with the products secreted by the kidneys of the breathing animals. Urea represents carbonate of ammonia from which the elements of two atoms of water have separated; allantoin represents oxalate of am- monia, from Avhich the elements of three atoms of water have separated." We now proceed to the consideration of a few of the most important products of nitric acid with uric acid. Alloxan. One part of dry uric acid is gradually added to four parts of nitric acid of spec. grav. 1'42 — 1'5, by which it is dissolved with eflervesceuce, and the production of heat. The whole liquid is soon converted into a solid crystalline mass of alloxan. Its formula is C^ H^ N„ O,,^. It is very soluble in water, reddens vegetable colours, and causes a purple stain on the skin. Its formation may be explained in the following manner. We have already shown (see Urea,) that urea is con- 58 ORGANIC CONSTITUENTS. verted by liyponitrous acid into water, carbonic acid, and nitrogen. Hence, if we suppose that the 2 atoms of uril (bearing in mind that m"ic acid = 2U1. + 1 at. urea,) take up the 2 at. of oxygen, which the nitric acid has given off in the formation of hyponitrous acid, and 4 at. of water, we obtain the formula of alloxan, for 2U1 (= C^ N, OJ+4HO + 2 O = C^ H^N^O,,^. Parabanic acid is obtained by treating one part of uric acid, or one part of alloxan in eight parts of nitric acid, evaporating to the consistence of a syrup, and allowing it to stand for some time, when it yields colourless crystals which may be purified by recrystallization. Its formula is C^ N, 0^ + 2 HO. It is formed by the action of hyponitrous acid on the urea of the uric acid ; the 2 at, of uril take up 4 at. of oxygen, and 2 at. of water, and yield 2 at. of carbonic acid, and 1 at. of hydrated parabanic acid : thus 2Ul + 2HO + 40 = 2CO,^ + (C, N^ 0^ + 2 HO.) Or it may be regarded as produced by the action of oxygen on alloxan, for C, H^ N,, 0,„ + 20 = 2CO., + 2HO + (C, N^ 0, + 2H0.) Oxaluric acid is obtained by boiHng parabanic acid in a solu- tion of ammonia. If the mixture be evaporated and allowed to cool, crj^stals of oxalurate of ammonia wiU separate them- selves. On the addition of an acid to a concentrated solution of this salt, oxaluric acid is separated as a crystalline powder. Its formula is Cy H^ N„ O, + HO. It is formed by the addi- tion of 2 at. of water to the constituents of parabanic acid : it contains further the elements of 2 at. of oxalic acid, and 1 at. of urea, and by boiling in water is completely decomposed into free oxalic acid, and oxalate of urea. Liebig observes that "when mic acid is subjected to the action of oxygen, it is first resolved into alloxan and urea ; a new supply of oxygen acting on the alloxan causes it to resolve itself either into oxalic acid and urea, or into oxaluric and parabanic acids, or into carbonic acid and urea," (Animal Chemistry, p. 137.) The reactions which we have already given are sufficient to explain this statement. We have shown that — Uric acid = 2 Ul + urea, and alloxan = 2 Ul + Oj -f 4 HO ; consequently, Uric acid -\-0^-\- A HO = alloxan + luea. MUREXAN. 59 Moreover, Alloxan = iirea + Cg Og (see their respective formula;) ; therefore, Alloxan -|- = lu-ea + Cg Og = urea -\- 3 at. oxalic acid, and Alloxan + 64 = urea -j- Cg 0,^^ urea + 6 at. carbonic acid. Also, Alloxan -j- Oj = parabanic acid + 2 HO + 2 COj = oxalui-ic acid -(- 2 at. carbonic acid. Hence, Uric acid -j- 4 HO -f- O3 = 2 at. urea + 3 at. oxalic acid. Uric acid + 2 HO -f 04 = 2 at. urea -[- parabanic acid + 2 at. carbonic acid. Uric acid + 4 HO + 0^= 2 at. urea -j- oxaluric acid -j- 2 at. carbonic acid. Uric acid -|- 4 HO -|- Og = 2 at. urea -f- 6 at. carbonic acid. These formulse express laws of mucli importance in urinary- pathology ; they show us that if an abundant supply of oxygen be given to the uric acid, carbonic acid and lu'ea may be ob- tained j if a smaller quantity, oxalic acid and urea ; and if none be given the acid remains unchanged. Murexid [Pwjmrate of ammonia^ The best method of exhi- biting this substance is to evaporate a solution of uric acid in dilute nitric acid, until it acquu'cs a flesh-red colour : after it has cooled to 160*^ a dilute solution of ammonia must be added, till the presence of free ammonia is remarked by the odour. The solution is then to be diluted with half its volume of boiling water and allowed to cool : it crystallizes in short four-sided prisms, two faces of which reflect a green metallic lustre. It is insoluble in alcohol ; sparingly soluble in cold, but more readily in boiling water, on the cooling of which it crystallizes unchanged. It is soluble in caustic potash with a beautiful indigo-blue colour, which disappears with the evolu- tion of ammonia on the application of heat. The diff'erence between the views of Prout and Liebig regarding this substance is, that the latter considers it a distinct principle, while the former regards it as a combination of a peculiar acid (pmpuric) with ammonia. Prout's view has been strongly confirmed by the researches of Fritzsche, which are published in the Transac- tions of the Academy of Sciences of St. Petersburgh, for 1839. The formula assigned to this substance by Liebig and Wohler is C, , H,, N^ 0„. Fritzsche gives it the formula C„. H, N,, O, „ or 1*2 b 5 8 O 10 8 u 1 W Murexan or purpuric acid is prepared by dissohdng murexid in caustic potash by the aid of heat, Avhich is to be applied till 60 ORGANIC CONSTITUENTS. the blue colour disappears : dilute sulphuric acid is then to be added iu excess. It falls in crystalline scales of a silky lustre ; is insoluble in water and dilute acids, but is taken up by ammonia and the fixed alkalies. If a solution of murexan in ammonia be exposed to the air, it acquires a purple-red colour and deposits crystals of murexid: with an excess of ammonia it again becomes colourless, and is then found to contain oxalurate of ammonia. Its formula, according to Liebig and Wohler, is C^ H^ N„ O,; according to Eritzsche it is C,,. H^ N. 0^,^. The substances a\ liich have been described are only a few of the products of nitric acid on uric acid ; they have been selected as having a more practical bearing than the others. The fol- owing table exhibits the principal results of Liebig and Wohler^s admirable paper on this subject. a) On treating uric acid with cold concentrated nitric acid, we obtain alloxan, C^ H,^ N, O^^^ or 2Ul + 0,+ 4 HO. b) On treating uric acid Avith cold dilute nitric acid, we obtain alloxantin, C^ H^ N„ 0,„, or 2U1 +0+ 5 HO. c) On treating alloxan with sulphurous acid, we obtain thion- uric acid, C^ H^ Ng O,^ S,,. d) On treating thionuric acid, or thionurate of ammonia, with hydrochloric, or sulphm-ic acid, we obtain uramil, C3 H^ N3 O,,, or 2UI + NH3 + 2HO. e) On treating alloxan with sulphuretted hydi'ogen, we ob- tain first, alloxantin, and subsequently dialuric acid, C3H^N,^0,, or 2tJl + 4HO. /) On warming uric acid in eight parts of nitric acid we oh- toin jjarabanic acid, C^. N, 0^ + 2H0. ff) On boiling parabanic acid in ammonia, oxalurate of ammo- 7iia is generated, from which we can obtain oxaluric acid, C, N^ H3 O, + HO. A) On the addition of an alkali to a concentrated solution of alloxan, we obtain alloxanic acid, C^ H, N„ 0^-|-2H0. ?') By the precipitation of a solution of alloxan with boiling acetate of lead, we obtain mesoxalic acid, C^ O^. j) By heating a solution of alloxan with ammonia, we obtain rnycomelinic acid, C^ H^ N^ O . k) On heating uramil with dilute sulphuric acid, wc obtain nramilic acid, C,,, H,,, N O, . HIPPURIC ACID. 61 (/) On warming uric acid with nitric acid and saturating it witli ammonia, we obtain murexid, C,„ Hg N. O^. {m) On dissolving mnrexid in caustic potash and adding dihite sulphuric acid, we obtain murexan, Cg H^ N„ O.. 14. Hippuric Acid. Hippuric, or urobenzoic acid, is an ordinary, although not a constant, ingredient of the urine of the graminivora. It has been observed by Lehmann, Ambrosiani, and Eeich, in the urine of diabetic patients, and Bouchardat has found it in the same secretion in certain anomalous cases to which he has ap- plied the term " hippiuie." Liebig has recently asserted that it is a constant ingredient of healthy human urine ; and even if this statement be too general, there can be no doubt that it does very frequently occur in minute quantity in this secretion. Hippuric acid is readily obtained by evaporating the urine of the horse or cow to about one tenth of its volume, and adding sufficient hydrochloric acid to give it a decidedly acid reaction. Yellow or brown crystals of hippuric acid are almost immedi- ately deposited, which must be collected, dissolved in a hot solution of carbonate of soda, and filtered through animal char- coal. By the addition of hydrochloric acid to this sobition, (which must be concentrated, if requisite,) we obtain tolerably pure crystals of hippui'ic acid. This acid forms long transparent four-sided prisms, acumi- nated at the extremities; it is destitute of odour, and has a faintly bitter, but not an acid taste. It dissolves in about 400 parts of cold water, and in a much larger proportion in hot water, from which it recrystallizes on cooling. It is freely soluble in alcohol, less so in ether. A cold aqueous solution strongly reddens litmus. At a moderate heat, hippuric acid melts (without yielding water) into a colourless oily fluid, which, on cooling, solidifies into a crystalline milk-white mass. At a higher temperature the acid undergoes decomposition, and yields a crystalline sublimate composed of benzoic acid and benzoate of ammonia, while, at the same time, some red oily di'ops are produced, which develop a peculiar odour, resembling that of the Tonquin bean. Hydrocyanic acid is subsequently formed, and the previous odoiu- is replaced by a bitter-almond smell. The action of perchloride of iron on this acid is worthy of notice. On the addition of this reagent to a solution of hip- 62 ORGANIC CONSTITUENTS. puric acid^ a well-marked yellow colour is produced ; no such change is effected on the addition of this test to a solution of uric acid. On its addition to a solution of hippurate of potash, a copious orange- coloured deposit is thrown down^, which, on the application of heat, forms a red resinous mass, soluble in alcohol, but insoluble in water; when added to a solution of urate of potash, a precipitate is likewise thrown down, which is at first of a brownish red colour, but rapidly becomes yellow. The composition of this acid is represented by the formula^ C,3 Hg NO^ + HO. In its physical characters it strongly re- sembles benzoic acid, and there can be no doubt that these two acids have been often confounded : there is, moreover, a close analogy between them. They both belong to the benzoyl series, although the exact place of hippuiic acid cannot be at present assigned to it with certainty. Oxidising agents (as nitric acid, or sulphuric acid and biuoxide of manganese) convert hippuric into benzoic acid ; and a similar change occurs in the urine if it be kept for any time. Conversely, benzoic and cinnamic acids are converted in the organism into hippuric acid.^ Hippuric acid forms soluble crystallizable salts with the alkalies and alkaline earths. Diagnosis. Hippuric acid may be distinguished by its crys- talhne form, its solubility in alcohol, its behaviour when heated, and its reaction with perchloride of iron. Nitric acid wiU suf&ce to distinguish it from ui'ic acid. 15. Uric Oxide. Uric oxide, xanthic oxide, urous acid. This substance is a very rare ingredient in vesical calculi. It was discovered by Marcet, who gave it the name xanthic oxide ; it has since been met wdth by Laugier, Stromeyer, and Dulk, and it is said to have been recently detected in guano, by Unger. Urinary calculi which contain this ingredient are dissolved in caustic potash ; the m'ic oxide is precipitated from the filtered ' See Appendix I, Note 20. ^ Erdmann has sometimes found hippuric, and at other times benzoic acid, in the urine of the same horse. In all prohalnlity an excess of uourishment favours the production of this acid, for the urine of \vell-fed horses usually contains hippuric acid, while only benzoic acid can be discovered in the urine of horses employed for agriculti»-al purposes : sometimes, however, the latter contains hippuric acid on some days and not on others, without any perceptible cause. For Liebig's theory of the origin of hippuric acid, see 'Animal Chemistrv',' pp. 82, 140. URIC OXIDE. 63 solution by a stream of cavljonic acid. It forms a white pre- cipitate, wliicli, when di'ied, constitutes a pale yellow hard mass. It is represented by the formula' 0,^ H^ N^ O^. It differs from lu'ic acid in containing two atoms less oxygen, hence the name of lU'ic oxide. It dissohes in the alkalies, in small quantity in hot water, hydrochloric and oxalic acids, it is in- soluble in alcohol and ether, and produces no effect on test paper. It dissolves also in concentrated sulphuric acid with a yellow colour, and no precipitate is caused by the addition of water to the solution. It is soluble in hot nitric acid ivithout ef- fervescence,'^ and more slowly than uric acid. On carefully eva- porating this solution, a lemon-yellow residue is left, which is not reddened by the vapom* of ammonia, but which is dissolved with a reddish yellow colour by caustic potash, and leaves, on evaporation, a red residue. Muriate of ammonia throws doAvn a yellow precipitate from the potash solution. Uric oxide differs from uric acid in being insoluble in a dilute solution of carbonate of potash ; by this property these two substances may be separated from one another when they occur together. Dulk conceives that he has effected the metamorphosis of uric oxide into uric acid. The yellow nitric-acid solution of uric oxide was evaporated on a watchglass to a thick consist- ence. After a few days, small, hard, and transparent crystals appeared. A little of the portion which remained fluid, when heated on a platinum spatula over the flame of the spirit-lamp, assumed a blood-red tint, and in a few days the fluid which remained in the watchglass, exposed to the atmosphere, under- went a similar change of colour. He considers the small crystals which were formed to consist of alloxantin ; and, in support of his ^dew, he alleges the following facts. Cold water poured over them assumes a red tint, but does not dissolve them ; they are, however, perfectly soluble in boiling water, and, on the addition of ammonia to a hot concentrated solution, a reddish colour' manifests itself, which disappears on cooling. On con- centrating a portion of the solution to a few drops, mixing it with nitric acid, and then adding ammonia, a greenish salt separated itself. Lehmann instituted a series of experiments with the \dew of ' See Appendix I, Note 21. ' Dulk states that, in his case, the uric oxide did slightly effervesce. 64 ORGANIC CONSTITUENTS. obtaining uric oxide from uric acid by the action of deoxidising agents, but he failed in his attempt. 16. Cystin. Cystin, cystic oxide. Cystin is an occasional constituent of urinary calculi, and is sometimes found as a crystalline deposit in the urine. It may be obtained b}^ dissolving a portion of one of these calculi in caustic potash, and adding acetic acid to the boiling solution. As the fluid slowly cools, the cystin sepa- rates in six-sided, colourless, transparent scales. It may also be obtained in crystals from a solution in caustic ammonia, if left to evaporate slowly. The scales are then thicker, and may be considered as regular six-sided prisms. Cystin has an extraordinary composition. It contains 25 -55 of sulphur. Its formula' is C, H^. N O^ S„. It has neither an acid nor alkaline reaction ; when heated, it does not melt ; takes fire with a blueish flame, and gives off a very characteristic odour; is very slightly soluble in water, and quite insoluble in alcohol; dissolves in dilute sulphuric, nitric, hydrochloric, phosphoric, and oxalic acids, the saturated solutions yielding, on gentle evaporation, salt-like compounds of cystin and the acid ; these compounds separate in diverging crystalline needles, which have an acid taste, and are not very durable. Cystin dissolves readily in the fixed alkalies, and forms, on evaporation, granular crystals. It dissolves in caustic ammonia, but does not combine with it. Carbonate of ammonia, is the best reagent for throwing it down from its acid solutions, as it does not dissolve cystin. It may be removed from an alkaline solution by acetic, citric, or tartaric acid, with none of which it enters into combination : acetic acid is generally used. Diagnosis of cystin. Cystin may be recognized by the peculiar crystalline form^ (six-sided plates) in which it separates from its solutions ; by its insolubility in water and alcohol ; by its behaA-iour towards acids; and by its peculiar odour on burning. Its crystalline form and its behaviour towards acids distinguish it clearly from uric acid : these tests, as well as its solubility in hydrochloric and oxalic acids distinguish it from uric oxide. • See Appendix I, Note 22. * 1 once observed an amorphous deposit of urate of ammonia yield, on the addition of acetic acid, perfectly regular hexagons. This form is also depicted hy Rigby, in l)is work on Dvsmenorrhoea. ANIMAL SUGARS. 65 CLASS II. NON-NITROGENOUS CONSTITUENTS. 1. Animal Sugars. a. Sugar of milk is an integral constituent of the milk of the mammalia^ and is a very rare ingredient of any other fluid. It has never been detected with certainty in the blood ; although Simon was led to believe, from the taste, and the carbonization with sulphuric acid, that he had once separated it from calves' blood. Prout once found it in the liquor amnii of a cow, but this is the only instance in which it has been detected in that fluid. A more remarkable case is recorded by Koller,^ who removed a milky-looking fluid from between the tunics of the testicle, which contained sugar of milk. Sugar of milk may be obtained by evaporating whey to the consistence of a syrup, and setting it aside for some weeks in a cool place. Granular crystals of sugar of milk will be spon- taneously deposited. In order to procure them in a state of purity they require several solutions and recrystaliizations. Sugar of milk is white, and crystallizes in right four-sided prisms usually terminated by four-sided pyramids, which are semi-transparent, and have a spec. grav. l'o43. It dissolves in 5 or 6 parts of cold water, and in 2*5 parts of boiling water, without forming a sp'up. A solution communicates a more decidedly sweet taste to the tongue than the crystals them- selves. Sugar of milk is unaltered by the air, loses nothing at 212°, and is insoluble in alcohol and ether. At a high temperature it fuses, swells up, and develops a sweetish but very pungent odour. It burns with a palish blue flame, and leaves after incineration, an ash consisting of the carbonates, sulphates, and phosphates of lime and potash, amounting to about 'Ig of the sugar. According to Simon, the sugar of woman's milk does not melt on being exposed to a high tem- perature, but only becomes tough and fibrous. By digestion in dilute sulphuric or hydrochloric acid, or in 1 This fluid contained in 1000 parts : Butter 16-49 — casein 20-31 — sugar of milk 31-50— chloride of sodium 2-78 — lactate of soda 0-74 — sulphate of potash 1-51 — sul- phate of soda 0-37 — carbonate of lime 0-38 — carbonate of magnesia 0-47 — phosphate of magnesia 0-89. (Wagner's Handworterbuch, t. i, p. 25.) 5 66 ORGANIC CONSTITUENTS. acetic or citric acid, sugar of milk becomes converted into sugar of grapes. By nitric acid it is decomposed into mucic/ oxalic^ saccharic, and carbonic acids. On the addition of casein, animal membrane, diastase, &c. to a solution of sugar of milk^ lactic acid is formed and the fluid begins to ferment. Crystals of sugar of milk may be represented by the formula Cj^ Hj^ O,,. At a temperature of 212° the crystals lose 11-9^, or two equivalents of water. Consequently the formula for anhydi'ous sugar of milk is C, H,„0,„. j3. Diabetic sugar exists in the blood and urine, and occa- sionally also in the sweat"^ of persons suffering from diabetes. It may be obtained by adding basic acetate of lead to the urine, filtering, precipitating any excess of lead by sulphui'ctted hydrogen, evaporating, extracting the syrupy residue with alcohol, and allowing the alcoholic solution to crystallize. It requires several crj^stallizations to obtain the sugar in a state of purity. Diabetic sugar usually crystalhzes in wart-like knots, or plumose groups, of minute, rhombic, transparent crystals. It is white, devoid of odour; in sweetness and in solubility in water^ it ranks between cane sugar and sugar of milk. It is more soluble in dilute alcohol than sugar of milk, but is insoluble in absolute alcohol and ether. Diabetic sugar in a crystalline state is represented by the formula C^,, H,^ O^^; in this condition it contains two equivalents, or Oj^ of water, so that its correct formula is Cj„ H,„ 0,„-f2H0. It is identical in its chemical compo- sition with sugar of grapes. Diabetic sugar forms a beautiful crystallizable compound with chloride of sodium. On satm^ating diabetic urine with common salt, and leaxing it to spontaneous evaporation, crystals three foru'ths of an inch in diameter may be ob- tained. They are not very regular in their form, but most of them are six-sided double pyramids. These crystals are hard, easily pulverizable, transparent, of a combined saltish and sac- ' It is worthy of remark that sugar from different sorts of milk yields varying quan- tities of mucie acid. "^ A. ease in which sugar was detected in the sweat of a diahetic patient is recorded by Nasse, Rhein. Corresp. Blatt. 1842. Nr. 6. ^ Simon found that one part of diahetic sugar dissolved in 1"3 of water at 53°. ANIMAL SUGARS. 67 charine taste, and dissolve in about S7 parts of cold water, and slightly in alcohol. The formula for this combination is C,. H,.^ O,^, 2H0 + C,.^ H,^ O,^, NaCl. Tests for Diabetic Sugar. ^ a. Hiinef eld's test. Place 4 oz. of the suspected urine in a glass exposed to the sun^s rays, and add about 6 drops of a tolerably strong solution of chromic acid. In a few minutes if sugar be present, the mixture, previously orange red, becomes brownish, and soon after as- sumes a bistre-brown colom\ These changes take place much more quickly if the mixture of urine and chromic acid be gently warmed before exposure to light. This test depends for its action upon the deoxidizing power of the sugar, by which the chromic acid is reduced to oxide of chromium ; for, after warming the mixture, the addition of a few drops of liquor jjotassce produces a copious deposit of the green oxide. There is an important objection to this test which renders all its indications liable to serious fallacy, depending upon the fact, that all urine containing a normal proportion of colouring matter deoxidizes chromic acid ; and consequently urine, whether saccharine or not, will partially convert this acid into the oxide. This change certainly does not occur so readily in non-saccha- rine urine as in a diabetic state of that fluid, but still is suffi- ciently marked to prevent Hiinefeld^s test being regarded in any other light than a fallacious one. b. Runge's test. Allow a thin layer of the suspected urine to evaporate on a white surface, as the bottom of a white plate, and, whilst warm, drop upon the surface a few di'ops of sulphuric acid, previously diluted with 6 parts of water. With healthy urine, the part touched with the acid becomes merely of a pale orange colour, from the action of the latter upon the colouring matter of the urine ; whilst if sugar be present the spot becomes deep broTVTi, and soon black, from the decomposition of sugar by the acid, and consequent deposition of carbon. This test is stated to be so delicate, that 1 part of sugar dissolved in 1000 ' The following observations are principally taken from an excellent paper, l)y Dr. G. Bird, on the detection of a diabetic state of the urine, in the London jMedical Gazette for 1843. We have omitted to notice the test afforded by the rotatory power of a solution of sugar on a ray of polarized light, as it has been shown by Dr. Leeson to afford very fallacious results. Memoirs of the Chemical Society, Part 7. 68 OUGANIC CONSTITUENTS. of urine can be readily detected ; and even when mixed witli 2000 parts the indications arc tolerably distinct. According to Dr. G. Bird, the presence of albumen causes the acid to yield a tint nearly resembling that produced by sugar. c. Moore's test depends on the conversion of diabetic sugar into brown melassic (or perhaps sacchulmic acid) under the in- fluence of a caustic alkali. Place in a test tube about two drachms of the suspected urine, and add nearly half its bulk of liquor 'potass(B. Heat the mixture over the spirit-lamp, and allow it to boil for a minute or two ; the previously pale urine will become of an orange-brown or even bistre tint, according to the proportion of sugar present. This reaction has been long known, but Mr. Moore deserves the credit of bringing it pro- minently forward. d. Trommer's test. Add to the suspected urine contained in a large test tube, a few drops of a solution of sulphate of copper ; a very inconsiderable troubling generally results, pro- bably from the deposition of a little phosphate of copper. Sufficient liquor potass(R should then be added to render the whole strongly alkaline ; a grayish green precipitate of hydrated oxide of copper falls, which, if sugar be present, wholly or partly re- dissolves in an excess of the solution of potash, forming a blue liquid, not very unlike the blue ammoniuret of copper. On gently heating the mixture nearly to ebullition, the copper falls in the state of suboxide, forming a red and copious precipitate. If sugar is not present, the copper is deposited in the form of black oxide. This test is founded on a fact long known, but not previously applied to the detection of sugar, of the power possessed by some organic matters of reducing oxide of copper, as well as some other oxides, to a lower state of oxidation. It certainly is the most delicate of all the chemical tests hitherto proposed for the detection of sugar in the urine, and will readily detect it in diabetic urine, even when very largely diluted. It is important in using this test that no more of the solution of sulphate of copper be used than is sufficient to afford a de- cided precipitate on the addition of the liquor potassce. If this precaution be not attended to, a part only of the black oxide will be reduced to red suboxide, unless a very large quantity of sugar is present, and thus the indications afforded by this test will be rendered indistinct. FATS. fiO e. Fermentation test. The development of the vinous fermen- tation on the addition of a little ferment or yeast to a fluid, has long been applied as a test for the detection of sugar. It was suc- cessfully employed by Professor Leopold Gmelin of Heidelberg ■ for the detection of sugar in the animal fluids after the inges- tion of amylaceous food. Dr. Christison has the merit of particularly suggesting the apphcation of fermentation for the discovery of a diabetic state of the urine. When a little yeast is added to healthy urine exposed to a temperature of about 80% no other change occurs for some time, except the development of a portion of carbonic acid me- chanically entangled in the yeast. When sugar is present in the urine thus treated, it soon becomes troubled, a tolerably free disengagement of bubbles of carbonic acid takes place, and a frothy scum forms on the surface of the fluid, which evolves a vinous odoui*. These changes take place with great rapidity, even when the quantity of sugar present is very small. If the evolved carbonic acid is collected, the quantity of sugar in the urine may be determined by measuiing it, as a cubic inch'^ of the gas very nearly corresponds to a grain of sugar. In the absence of a mercurial trough, the carbonic acid may be determined by the increase of weight^ of Liebig's bulb-appa- ratus, charged with a solution of potash. f. Test afforded by the growth of the torula. If urine containing the smallest proportion of sugar be exposed for a few hours to a temperature above 70", and a drop taken from the sm^face be examined under the microscope, numerous very mi- nute ovoid particles will be discovered. In the course of a few hoiu-s more they become enlarged, and appear as distinct oval vesicles, which rapidly become developed into that species of confervoid vegetation, to which the term torula has been applied. 2. Fats. Under the name of " fats," we include various non-nitro- genous compounds, which are insoluble in water, but soluble in hot alcohol and ether. 1 Recherches Experimentales sur la Digestion. Paris, 1826. Part I, p. 202. 2 100 cubic inches of carbonic acid gas coiTCspond with 106-6 grains of diabetic sugar. 3 100 grains of carbonic acid indicate 225 grains of diabetic sugar. The gas must be passed through a tube containing chloride of calcium. / 70 ORGANIC CONSTITUENTS. Some of these fats possess the property of being decomposed by strong bases, especially by tlie alkalies, and by oxide of lead ; in this case one of the two principal constituents separates itself, while the other (an acid) combines Avith the base, forming a soap Avitli the alkalies and a plaster with oxide of lead. Hence it follows that those fats which, on account of this pro- perty, are termed saponifiable, are, like the salts, formed of an acid and of a base ; these acids and their bases being themselves the oxides of compound radicals, probably of hydro-carburets. There are other fats which cannot be decomposed in this manner : they are termed non-saponifiable fats. We shall commence with the consideration of the former class, the saponifiahle or true fats. a. Fatty Bases. We are acquainted with three bodies, oxides of different radicals, which act the part of bases in the animal fats. These are (jlycerin, the oxide of cetyl, and cerain : the first of these three is the most widely distributed, and forms the base of the fats of the human body ; the oxide of cetyl exists in spermaceti, and cerain in bees^ wax. We shall restrict om* remarks to glycerin. Glycerin^ is separated from the fats by the act of saponifica- tion, when the acid with which it was combined enters into combination with the new base. The best method of obtaining it in a state of purity is to boil an animal fat with oxide of lead. The salt of lead which is formed is insoluble in water, (it is, in fact, a plaster,) while the glycerin remains in solution. After remonng any excess of lead by a current of sulphuretted hydrogen, we must evaporate the fluid in vacuo over sulphuric acid. The glycerin, prepared in this manner, is a clear uncrystal- lizable fluid, of spec. grav. 1*28, of a yellowish colour, devoid of odour, of a marked sweet taste, very soluble in water and alcohol, but insoluble in ether. It burns with a clear blue flame. It is considered as the hydrate of an oxide of a radical, glyceryl (Cg H^), which has not yet been isolated. Its compo- sition is expressed by the formula" C^. H^ 0, + HO. Stenhouse ' This substance, glycerin, is united in each fat with a difterent acid, and hence the fats may he considered as salts of glycerin. ■■^ See Appendix I, Note 23. FATS. 71 assigns the formula C^ H.^ O, or C^ H, + 0, and Redtenbacher Cg H^ 0„+4H0, to this substance. At an elevated tempera- ture, a portion of the glycerin is distilled without change, while the rest is converted into empyreumatic oils, acetic acid, and combustible gases, leaving a carbonaceous residue. Diagnosis. Glycerin may be recognized by its taste, by its solubility in water and alcohol, but not in ether, by the absence of crystallization, and by the strong white precipitate which is formed upon the addition of nitrate of mercury. |3. Fathj Acids. We shall now proceed to consider the fatty acids, Avhich, in combination with glycerin, constitute the various fats and oils. Two simple fats, stearin and maryarin, and a simple oil, olein, with their respective acids, the stearic, maryaric, and oleic, are especially deserving of notice. The researches of Redtenbacher, Varrentrap, and Bromeis, have shown that the two former of these acids ai'e in reahty constituents of the same radical, in diflFerent stages of oxidation. This radical is termed maryaryl, and its constitution is expressed by the formula C^^ H^^. In addition to these acids, we find certain fatty acids in butter, which, in combination with glycerin, form distinct fats. Fremy has likewise described a peculiar acid of this natui'e as existing in the brain, to which he has given the name cerebric acid. We omit the consideration of various other fatty acids, which are only met with in particular animals and in the vege- table kingdom. a. Maryaryl and its oxides — stearic and maryaric acids. On saponifying mutton-fat with potash, dissolving the soap which is thus formed in six parts of hot water, and then adding forty-five parts of cold water, and allowing the solution to rest at a temperature of 60^, we obtain, after some Little time, a lamellar precipitate of bistearate of potash, mixed with bimar- garate, and a little oleate of the same base. On neutralising the free potash in the supernatant fluid with an acid, and proceeding as before, we obtain a precipitate of the margarate and stearate of potash. After this process has been repeated several times, nothing but oleate of potash remains in solution. The preci- pitates must be washed, dried, and dissolved in boiling alcohol. On cooling, the stearate of potash, which is the least soluble, 72 ORGANIC CONSTITUENTS. separates first, mixed with a small quantity of the margarate. The more frequently the solution is repeated the more certain are we that ultimately the whole of the margarate will be re- tained in solution. The pure stearate of potash is decomposed by warm dilute hydi'ochloric acid ; and the stearic acid which precipitates is to be washed in water and dissolved in boiling alcohol, from which it crystallizes, on cooling, in white brilhant scales. By the same process the margaric acid is separated from the pure mar- garate of potash. Margaric acid is obtained most easily from human fat, which contains a very large amount of margarin. Stearic acid mehs at 158^^. The specific gra^dty of the acid in its sohd state is 1-01. It is perfectly insoluble in water, but dissolves readily in ether as well as in boihng alcohol, in Avhich, on cooling to 122°, crystals begin to form. Its solution exhibits a mild acid reaction toAvards litmus ; in the sohd form it burns with a clear flame, like wax. The leading difference between margaric and stearic acids is the greater fusibility of the former, which becomes liquid at 140°. Its crystals assume an acicular form, and are smaller and less brilliant than those of stearic acid. Stearic acid is represented by the formula' C^.^ H^^ O.. In its crystalline state it is combined with 2 atoms of water (forming the hydrate of stearic acid), which it gives up on uniting Avith a base. Margaric acid is represented by the formula C^^ H33 O^. The hydrate contains only 1 atom of water. The radical of these two acids, margaryl, is represented by the formula C,^ H33 (M) Hence, margaric acid = M + O3 and stearic acid = 2 M + O^ If we treat stearic acid for some time Avith nitric acid at a temperature of 212°, it becomes completely converted into margaric acid. A similar, although not so perfect an effect is produced by sulphuric and chromic acids. The stearic and margaric are very weak acids ; at an elevated temperature they have the poAver of expelHug carbonic acid ' Sec A])pen(lix I, Note 24. FATS. 73 from its combinations ; most of the other acids, however, de- compose their salts. The alkahne and neutral stearates and margarates are soluble in water; the acid salts (for there are bi- and even quadri-stearates of potash and soda) are not soluble in this fluid, neither are the salts formed with other bases. The stearates of barj^ta, strontia, and lime are white, insipid, and inodorous powders. The neutral stearates of potash and soda occur in many of the animal fluids, especially in the bile. We have already observed that most of the fats are formed by a combination of stearic and margaric acids with glycerin. The bisteurute of glycerin, or, as it is usually termed, stearin, is best obtained from mutton suet, either by washing it with ether as long as anything is dissolved, or by mixing up melted suet with six times its volume of ether, and subjecting the mass, when cold, to strong pressure. In both these processes the oleiu, which is fluid at the ordinary temperature, is removed, and the stearin remains behind, although seldom in a state of purity. Steaiin melts at 144°. It is insoluble in water, and only dissolves in alcohol Avith the aid of heat. It dissolves very readily in boihng ether ; but, as the ether cools, nearly the whole of the stearin is again precipitated, and at 59° it only retains the one hundred and twenty-fifth part of its Aveight in solution. It is also soluble in the fatty and volatile oils, and in pyroacetic spirit. The stearin, after being melted down, and allowed to reassume its sohd form, appears as a white, semitransparent, uncrystalHne mass, not unlike wax. Acids and bases convert it into stearic acid and glycerin. The for- mula for stearin is Cj^„ H^^, Oj. ; it is equivalent to 1 Atom of glycerin . . Cg H, 0^ -i 2 Atoms of stearic acid . 6,35 H,32 0,o >- = C,42 Hj^i 0,7 2 Atoms of water . . H^ Oj J The bimargarate of glycerin, or margarin, is obtained by submitting to spontaneous evaporation the ethereal solution from which the stearin has been separated. The flocculi of margarin that separate themselves must be freed from olein by pressui'e. INIargarin melts at 118°. Its solubility in ether is much greater than that of stearin ; at 74° it is perfectly soluble in 5 parts of ether. It is nearly as soluble in alcohol at the ordinaiy temperatm-e as at the boihng point. In other respects it closely resembles stearin. 74 ORGANIC CONSTITUENTS. The formula for margarin is C^g H.^ 0^,,, corresponding with 1 Atom glycerin . . , Cg H^ O5-1 2 Atoms margaric acid . . C^o Hg^ Og 1-= C-g H-,- Oi., 1 Atom water . . . H O J 6. Oleic acid. This acid is obtained from the oleate of potash^ which is produced during the preparation of the stearate and margarate of potash, and remains in solution. It must be separated by the addition of a mineral acid, and then well washed and shaken in hot water. It is an oily fluid, of a clear yellow colour, and does not assume a solid form until it is cooled several degrees below the freezing point of water. At about 19° or 20^ it congeals into white acicular crystals. It is very acid, and has a rancid odour and taste. Its specific gravity is 0-898. It is not soluble in water, but dissolves in alcohol in all proportions, and the spiiituous solution acts freely on litmus paper. It combines with stearic and margaric acids in all proportions, and the perfect separation of the acids in such cases is not very easy. Its composition, according to Varrentrap, is represented by the formula C^^ H^^, 0^ + HO. Oleic acid may be distilled in vacuo without undergoing any change; but if atmospheric air be admitted, a small portion only passes over unaltered, while the greater part is decom- posed, and some carbon remains in the retort. f\ At. sehacic acid C,o Hg O4 3 At. carbonic acid C3 Og 2 Atoms hydrated oleic acid, C^^ U.^ 0,o, produce ^ u^^^j-ocarburet C, II7, >"• Residual carbon C^ Sebacic acid was formerly considered as a product of the destructive distillation of all fatty bodies, but it has been shown by Redtenbacher to arise only from oleic acid. Oleic acid removes carbonic acid from bases. The oleates do not crys- tallize; those which are soluble appear as soft, easily fusible bodies, and are more soluble in alcohol than in water. The oleates of potash and soda, if treated with a sufficient quantity of water, become reduced to binoleates, and a portion of the base is freed. The oleate, as well as the stearate of soda, exists in the bile. The bhioleate of glycerin, usually termed olein, exists in small quantity in the various solid fats, but forms the principal mass of the liquid fixed oils. It exists as an oleaginous fluid, and varies in some respects, especially in regard FATS. 75 to the point of fusion in the fats of different animals. Chevreul describes the olein of human fat as a colourless oil, devoid of odom', and of a sweetish taste, which retains its fluid state at 25°. At a lower temperature it assumes a crystalline acicular form. Its specific gra\dty at 59° is 0-913. One hundred parts of boiling alcohol dissolve 123 of olein; when the solution cools to 170°, it becomes turbid. It is readily soluble in ether, bnt perfectly insoluble in Avater. It burns with a clear flame. It dissolves camphor, phosphorus, selenium, the ethereal oils, benzoic and many other organic acids. Its composition is re- presented by the formula C^^ H^. Oj., and is composed of 1 Atom glycerin . . Cg H^ Og -| 2 Atoms oleic acid . C^g H^g Og V-= C94 Hgj 0,5 2 Atoms water . . II.^ O^ ■» c. Butyric and its allied acids. Butter contains four volatile acids, which stand in a very simple relation to each other, namely, butyric acid = C^ H^ O^, caproic acid = C,.^ H,„ O^, capryllic acid = C^g H^^ O^, and capric acid = C,,, H,^, O^. Butter sometimes affords, instead of butyric and caproic acids, a distinct acid, vaccinic acid, which appears to be equal to the sum of those two acids, minus 1 atom of oxygen, and is very readily decomposed into them. Two of these acids, the capryllic and vaccinic, were discovered only a few months ago, by Lerch, a German chemist. The following is the method that he gives for their separation : " Fresh butter is completely saponified with potash in a still, the soap decomposed in the vessel with dUute sulphuric acid, the head then luted on, and the aqueous liquid drawn off to within a fourth. Presh water is then added to it, which is again distilled off, and this operation continued as long as the water which passes over possesses any acid reaction. In this manner the volatile fat acids are carried over just as the essen- tial oils ; the action of the atmosphere is moreover entu*ely ex- cluded. From four to five pints of a milky hquid are obtained from a pound of butter, on the surface of which float drops of oil and particles of hard or smeary fat. The distilled water is immediately saturated in the receiver with barytic water, and allowed to stand well closed till the end of the distillation. When the distillation is finished, the still is cleansed, and the liquid saturated with barytic water, evaporated in it, with the head on. 76 ORGANIC CONSTITUENTS. to about the twentieth part, and the still hot concentrated ley then reduced to dryness in a retort. " The saline mass obtained in this manner consists of two por- tions, one easy, the other difficult of solution. The more so- luble portion consists, according to circumstances, of butyrate and caproate of baryta, or solely of the barytic salt of vaccinic acid ; but in this case there is little or no butyric or caproic acid present. The portion difficult of solution consists of the baryta salts of two distinct acids, which Chevreul described to- gether as caprate of baryta. The more insoluble portion amounts to about the twentieth part of the soluble, and the en- tire mass to about the tenth part of the saponified butter. To separate the diff"erent salts, the residuary saline mass is boiled with about 5 or 6 parts of water ; one portion dissolves, the other remains behind. The solution of the readily soluble salts is set aside to crystallize ; if, on the first crystallization, the crystals which separate have the appearance of benzoate of lime, and do not effloresce, i. e. if they are caproate of baryta, the butyrate of baryta has still to be sought for in the solution ; but if nests of small crystals form, which quickly effloresce, and resemble nests of the native carbonate of lime, it is vaccinate of baryta, and it is then unnecessary to look for butyrate and caproate of baryta. " The circumstances under which butter contains vaccinic acid or butp'ic and caproic acids are not known. The butter of 1842, and likewise that of the following "ndnter, contained, in several experiments, not a trace of any other easily soluble salt of baryta than the vaccinate ; while the butter in the summer of 1843 contained no vaccinic acid, but only the other two. " The soluble saline mass, containing the butj^ic and caproic acids is dissolved in Avater and evaporated to crystallization, in order to separate them. Long silky needles, aggregated in bundles, separate even in the first crystallizations ; and if the solution has been sufficiently concentrated, nearly the wliole of the caproate salt is deposited. The entire solution solidifies to a paste of minute needles, which ai'c separated by pressure from the mother-ley, and purified by recrystallization. The remaining ley is now allowed to crystallize spontaneously, which is best eff'ected by exposure to the sun ; at first a little caproate of ba- ryta still separates, the form of the crystal then changes, laminae of mother-of-pearl lustre make their appearance, and all the FATS. n subsequent crystallizations are nearly pure butyrate of baryta, which is purified by recrystallization. " The saline mass of difficult solution is dissolved in just so much boiling water as is requisite for complete solution, arid is filtered while hot. During the cooling, the liquid becomes filled with minute scales of caprate of baryta, of a fatty lustre, which subside in the form of a crystalline precipitate. The decanted mother-ley is again evaporated one foin^th, when a fresh quan- tity of caprate of baryta separates. This salt is purified by re- crystallization. The mother-ley now contains the capryllate in solution ; it is evaporated by exposure to the sun, when the salt separates in minute granules and verrucous masses, which are obtained pure by recrystallization. " This is the best method of separating these salts from each other ; an absolute separation is impossible, for there always re- main mixed crystals and leys, which in small quantities are not worth while working." ^ The butyrate of baryta is much the most soluble of these salts, requiring only 2*77 parts of water. On decomposing it by adding dilute sulphuric acid to its solution we obtain butyric acid, in the form of a colourless or faintly yellow oleaginous fluid. Butyric acid possesses an unpleasant odour, which calls to mind at the same time that of acetic acid and of rancid butter. It is soluble in every proportion in water and alcohol, and more soluble in ether than the other acids of the same group. Its specific gravity is 0-963 at 59" ; it evaporates easily in the open air, boils under ordinary pressure at about 337'', and distils without undergoing any perceptible alteration. Its vapour is inflam- mable, and burns with a blue flame. A continued cold of 4" does not produce any change in the state of the butyric acid ; its taste is strongly acid and burning ; it attacks and disorga- nizes the skin in the same manner as the strongest acids. The chemical relations of this acid have been made an object of especial research by Chevreul, Pelouze and Gelis, and Lerch ; and numerous butjTates and butyric ether have been formed, and submitted to careful investigation and analysis. ' Ann. der Chem. und Pharm. xlix, p. 212, as translated in Number 45 of the Chemical Gazette. 78 ORGANIC CONSTITUENTS. The only compound of butj^ic acid tliat concerns us at present is the butyrate of glycerin, or butyrin, the essential fatty matter of butter. In order to isolate butyrin from the various com- pounds with which it is associated in butter, we must adopt the following method. Purified butter must be kept for some days at a temperatiu'e of about 66°. At that temperature olein and butyrin are liquid, Avhile the solid stearin forms a mass by degrees, so that the liquid portion may be decanted off. On this decanted oily matter its own bulk of absolute alcohol must be poured, the mixture must be left for twenty-four hours, and the temperature be regulated to 66°. On distilling off the al- cohol from this alcoholic solution a residue of butyrin is left, mixed with a little olein. A slightly acid reaction is usuall}^ ob- served, in consequence of the decomposition of a little of the butyrin into butyric acid. This may be removed by digesting the butyrin in a mixture of magnesia and water. A butyrate of magnesia, soluble in water, is formed, and the butp'in may then be obtained perfectly neutral. The removal of all traces of olein from Ijutyrin is nearly impossible. Butyrin occurs as a colourless oil, which solidifies at 32°, is soluble in cold alcohol, but not in water, is devoid of odour, and produces no effect on litmus. In a warm atmosphere it speedily decomposes, and yields butyric acid. M M. Pelouze and Gelis have recently shown that by a peculiar process of fermentation butwic acid may be obtained from sugar. They recommend the following as the best process for obtaining the largest possible amount of butyric acid from this source. " A small quantity of casein is mixed with a solution of sugar, indicating 10" on the saccharometer, and sufficient chalk to saturate the whole of the butyric acid which subsequently forms. This mixture is left at a constant temperature of from 77'- to 86°. It soon undergoes very considerable alterations ; the fermentation, at first viscous, subsequently lactic, gradually becomes butyric. These decompositions are sometimes successive, sometimes simultaneous, without its being possible to regidate their course. The disengagement of gases becomes more abun- dant, and analyses show that a period arrives when the free hydrogen amounts to a third of the vokime of the carbonic acid. At this period the butyric fermentation is in all its vigour ; when at last, at the end of some weeks, all disengage- FATS. 79 ment of hydrogen lias ceased, the operation is at an end, and the sohition tlien contains only butp'ate of lime/' The composition of butyric acid, its proportion which amounted in several experiments to above the third of the weight of the sugar, the Hberation of free hydrogen, and of carbonic acid (independent of that which is disengaged from the chalk,) admit of our supposing that, under the prolonged influence of ferments, sugar is decomposed in the following manner : Grape-sugar. Butyric acid. C,2 Hi, 0„ = Cg H, O3 + HO + 4 CO. + 8 H + 2 HO. This formula is merely intended to exhibit the final result, for several chemical processes 1 precede the formation of butyric acid. By combining the butync acid formed in this manner with glycerin, they obtained a fatty matter that seemed in all respects identical with butjTin, as described by Chevreul. Fibrin jdelds butyric acid as one of the products of its decomposition : the other products of its putrefaction are albumen, carbonic and acetic acids, and ammonia. It may like- wise be obtained by heating this substance with potash at a tem- perature of from 320" to 356". A small quantity of a volatile fattj^ acid forms, which remains in combination with the potash, whilst ammonia and other volatile products are disengaged. This acid has not jet been analysed, but it seems to possess all the properties of butyric acid. (Wm'tz.) Caproic acid is obtained from the caproate of baryta, which crystallizes in long silky needles, aggregated into bundles. It is an oily limpid liquid with the odour of sweat, and a sharp acid taste. Its spec. grav. is 0*922 at 72° ; it evaporates in the open air ; its boiling point is above 212", and it is soluble in 96 parts of water at 44!""6. It dissolves in alcohol and ether. ' It is well kno\^^l that if a small quantity of casein be introduced into a solution of cane-sugar or sugar of milk, lactic acid begins very soon to be formed. The butyric acid may be supposed to be formed in the following manner : 20 eq. of lactic acid (C,2o H,2o 0^^g) = 15 eq. of butyric acid (C,oo H,.,^ Og„) + GO 0. These 60 eq. of oxygen decompose 6 eq. of lactic acid, and we have — 6 (Cg Hg 0,0 -i- 60 = C36 H36 O96 = 3 CO., + 12 H -f 24 HO when the carbonic acid is exactly three times the volume of the hydrogen produced. 80 ORGANIC CONSTITUENTS. Capryllic acid, at the ordinary temperature, forms a smeary mags ; below 50" it crystallizes in needles, wiiicli are of difficult solution in water, have an acid and acrid taste, and a peculiar disagreeable odour. The baryta salt separates from hot solu- tions in brilliant laminse, but on spontaneous evaporation in white granules. It is anhydrous, is not affected by exposure to the air, does not fuse at 213", and is very sparingly soluble in water. Capric acid resembles capiyllic acid in its properties. The baryta salt crystallizes from hot solutions in minute fatty needles and scales, and on spontaneous evaporation likcAvise in scales, arranged in dendritic groups ; it is very difficult of solution, is anhydrous, and is not affected by exposure to the air. Vaccinic acid. Vaccinate of baryta separates in nests of crystals, which have already been described ; they contain water of crystallization, effloresce very readily in the air, become very similar in appearance to chalk, and diffuse a strong odour of butter, while pure caproate and butyrate of baryta do not effloresce in the least, and have scarcely any odour. Vaccinate of barji;a is soluble in water to about the same extent as butj^ate of baryta; the saturated solution is thick like oil. When vaccinate of baryta is dissolved in water, and again evaporated in a retort, it crystallizes from the solution unaltered; but if the crystals are exposed for some time to the air, they at last lose nearly all their odour, and no longer when dissolved crystallize on evaporation, but in their stead crops of caproate and butyrate of baryta are ob- tained. The same happens when a solution is exposed to the air for any length of time, or boiled in an open dish. No baryta separates in this change, no acid vapours are given off, and the solution remains perfectly neutral. Vaccinic acid therefore saturates exactly the same amount of barj^ta as the two acids which have originated from it ; the relative quantity of the caproate and butyrate of baryta formed is proportionate to the atomic weights of these two salts. If vaccinate of baryta is decomposed by sulphuric acid, with free access of air, and the separated acid removed by distillation, saturated with baryta, and set aside to crystallize, a mixture of caproate and butyrate of baryta only is obtained. On adding some solution FATS. 81 of silver to a solution of vaccinate of baryta^ a white caseous precipitate is formed, wliicli is soon reduced, and smells strongly of butyric acid. Vaccinic acid has, therefore, evidently the same capacity of saturation as caproic and butyric acids together, but probably contains less oxygen. In all probability these acids form compounds with glycerin, and exist in butter as distinct fats. The brain contains several distinct fats which have been examined by different chemists (Kiihn, Couerbe, Fremy,) and found to contain phosphorus and sulphur. Couerbe has given to these the names of eleencephol, cerebrot, cephalot, and stearaconot. Cephalot is the only one that is saponifiable, and which, therefore, comes under the categor}^ of the true fats. Its fatty acid is unknown ; in fact the whole subject of the brain-fats requires an entire revision. Fremy^ has described two fatty acids that exist in the brain in combination with soda, to which he has applied the names of cerebric and oJeopliosphoric acids. Of the bodies just described, those which act the part of bases, never occur naturally in an isolated state ; and those which act as acids, very seldom. Butyric acid occasionally exists in a free state in the urine, and, according to Gmelin, in the gastric juice, and occasionally in the cutaneous trans- piration. Lecanu states that the margaric and oleic acids exist in a free state in the blood. Some of the fatty acids, as already observed, exist in the bile and in the cerebral matter, in combination with soda, but they are most commonly found united with glycerin. The contents of the cells of ordinary adipose tissue are a mixtui'e of stearin, margarin, and olein ; and the marrow of the bones has a very similar composition. The relative propor- tions of these three substances varies in the fat of different animals, which is the reason of the different consistence of various fats. The more olein present, the softer and more liquid will the fat be : and those fats in which the olein forms the principal ingredient are called oils. Those of a mean con- sistence are most properly termed fats, while the harder ones ' Annales de Chimie, 1841. 82 ORGANIC CONSTITUENTS. are known as sitet. Stearin is the principal constituent of suet ; margarin of fat or lard. Human fat affords a good illustration of the proper fats. It solidifies at 62° ; but the consistence is not constant even in the same person — for instance, the fat of the kidneys is perfectly solid at 62°, while the fat of the sub- cutaneous tissue remains fluid as low as SO'^. The non-saponifiable fats. a. Cholesterin is a normal constituent of the bile, of the brain, and of the spinal cord. It has been found by Lecanu, Denis, Boudet, Marchand, and Simon, in the blood ; by Fromherz and Guggert in the vernioc caseosa ; by Breschet, Wohler, and INIarchand in hydrocele ; by Stromeyer in an encysted tumour in the abdomen of a woman ; by Breschet and Barruel in the ovary and testicle in a diseased state ; by Caventou in an abscess of the tooth; by Lassaigne in a scirrhous structure in the mesocolon ; by Guggert in fungus medullaris ; by Marchandinmedullaiy sarcoma; and by Drunty in a vesical calculus extracted from a dog. It sometimes exists in a state of solution, while in other cases it floats on the surface, either in the fonn of brilliant scales, or of sohd masses. It has never been found in any of the plants which are used for food; but Dumas has found a substance of a similar composition in the resin of the pine. In order to obtain it from biliary calculi, we must first treat these with boiling water, then tritiu'ate, dry and pulverize the residue, treat it with boiling alcohol, filter it while still hot, and allow it to cool very gradually. The cholesterin separates itself in the form of white, sparkhng, transparent scales. These should be collected in a filter, again dissolved in hot alcohol, and allowed to recrystallize. In this state it will be tolerably pure, Berzelius recommends the previous addition of a few drops of caustic potash or ammonia, in order to saponify any stearic or margaric acid that may be present. In order to obtain it from the brain, that organ must first be deprived of all its water, by being finely triturated and then placed upon the water-bath. This being fully accomplished it must be treated with ether, and afterwards with boiling alcohol, until these fluids cease to abstract anything more. As the alcoholic solution cools, a white powder is precipitated. By FATS. 83 gently distilling the ethereal solution^ a residue remains^ from Avhieh eholesterin may be taken up by boiling alcohol ; on mixing the two alcoholic solutions, evajiorating to one fourth, and allowing the mixture to cool, a portion of the fat separates in the form of a Avhite powder, which consists not merely of eholesterin, but also of a substance which is insoluble in cold ether, the cerebrot of Couerbe. If, therefore, we treat this fat with ether, the eholesterin dissolves, while the cerebrot remains unacted on. By evaporation we obtain the eholesterin in a crystalline state, and by dissolving it in boiling alcohol and allowing it to recrystallize on cooling, we obtain it in a state of purity. On slowly cooling its alcoholic solution, eholesterin crystal- lizes in dehcate white nacreous scales. It is devoid of taste and smell, is insoluble in water, but dissolves in alcohol and in ether. According to Chevreul, 100 parts of boiling alcohol of 0-816 dissolve 18 of eholesterin; if alcohol of 0-840 be used only 11*24 parts are taken up : on cooling, the greater part is deposited. Kvihn states that 1 part of eholesterin is soluble in 12-1 of ether at 32°, in 3-7 parts at 59°, and in 2*2 parts of boiling ether. Cholesterin is perfectly neutral, of about the same specific gravit}^ as water, and at 280° melts into a coloui'- less fluid without undergoing any decomposition. Crj^stallized cholesterin contains about 5-2|^ of water. It burns with a clear flame, like wax, and one of its most striking characteristics is, that it is not affected by a solution of caustic potash. Its composition is represented by the formula Cg. H^^ O. b. Serolin. This name was given by Boudet to a fatty matter which he discovered in the blood. It has been more recently found and described by Lecanu and Sanson. In order to exhibit it, blood must be first evaporated to dryness on the Avater-bath, and the residue treated with water as long as anything continues to be taken up. It must then be dried, pulverized, treated with boiling alcohol, and filtered while hot. On cooling, the alcohol deposits this fat in flocculi. It must be collected on a filter, and washed with cold alcohol. Boudet assigns the following characteristics to serolin. It forms flocks of a fatty nacreous appearance, is perfectly neutral, and melts at 97°. On exposing it to a higher temperature, a portion is distilled unchanged, while another part is decomposed into 84 ORGANIC CONSTITUENTS. ammoniacal vapour. In water it is perfectly insoluble, in hot alcohol of 'SoS it is only slightly soluble^ and separates on cool- ing into its original flocculeut appearance, since cold alcohol exerts no solvent influence over it. It dissolves readily in ether. It does not form a soap with caustic potash. Lecanu describes the serolin obtained from human serum, as a white, but not nacreous, substance, which melts at 95°, is soluble in ether, but not in watery alcohol. It may be distinguished from other fats by its insolubility in cold alcohol ; from cholesterin, by its lower point of fusion. Diagnosis. The difi"erent fats and fattj^ acids are distin- guished by their fusing points, and by their varying degrees of solubility in alcohol and ether. Lactic, Oxalic, and Acetic Acids. 1 . Lactic acid is regarded by most chemists as a constituent of almost all the fluids of the animal body. The following is the method recommended by Mitscherlich,^ for the exhibition of pure lactic acid. Sour whey must be evaporated to about one sixth of its volume, and filtered ; the phosphoric acid precipitated by lime, and any excess of lime separated by oxalic acid. After filtration, the liquid must be evaporated to the consis- tence of a thick syrup, and the lactic acid extracted with alcohol. The alcohol must be removed by evaporation, and the residue dissolved in water mixed with carbonate of lead. In this manner a solution of lactate of lead is obtained, which, after filtration, must be decomposed by sulphate of zinc. Sulphate of lead is immediately precipitated, and lactate of zinc remains in the solution, which must be filtered and evapo- rated to incipient crystallization. In this manner we obtain crystals of lactate of zinc, a salt only slightly soluble in cold water. Lactic acid may be obtained by converting the lactate of zinc into a lactate of lime or baryta, carefully removing the base by the addition of sulphiu"ic acid, and cautious evaporation. Pure lactic acid is a colourless liquid, soluble in every pro- portion in water and alcohol, of a purely acid taste, and so strong and biting as to be almost insupportable. Its formula^ is C, H, O,, or C, H^O, + HO. ' Lehrbucli der Chemie, 1837, p. 512. * See Appendix I, Note 25. ACETIC ACID. 85 At a red heat lactates Avith fixed bases are converted into carbonates : 100 parts of the carbonates of potash and soda cor- respond to 180"9 and 201 "1 parts of the respective lactates of those bases. There is no ready test by which we can detect the presence of lactic acid : it is chiefly distinguished by its negative pro- perties. Rules for the quantitative determination of this acid and its salts will be found in the chapters on the different fluids in which it occurs ; they are founded with various slight modi- fications on the method that we have given for the exhibition of the acid. 2. Oxalic acid is not one of the normal constituents of the animal organism; it is however^ when combined with lime, a very common ingredient of morbid urine, and of urinary calculi. Oxalate of lime, when obtained by the addition of a soluble oxalate to a salt of lime, occurs as a white amorphous powder, insoluble in water, alcohol, oxalic and acetic acids, but soluble in hydrochloric and nitric acids without effervescence. It leaves, when heated to incipient redness, a white residue of carbonate of lime, from which the amount of oxalate may be easily calcu- lated, for 100 parts of carbonate of lime correspond with 128-9 of oxalate of lime. After a prolonged exposure to a higher tem- perature, the carbonic acid is expelled, and caustic lime remains. The occurrence of oxalate of lime in a crystalline state in urinary sediments has been shown, by Dr. G. Bird, to be much more frequent than was formerly supposed; in fact, althoudi the beautiful octohedi-al forms in which it occurs had been noticed some years ago by Vigla, Donne, and other French observers, it was not until the appearance of Dr. G. Bird's papers in the ' London Medical Gazette' for 184^2, that their chemical nature was fully established. 3. Acetic acid has been found by Tiedemaun and Gmelin in the gastric juice, by Thenard in the sweat, by Simon in the fluid of pemphigus and in saliva, and is asserted by some chemists to be a constituent of urine. For its chemical cha- racters we must refer to any of our systematic treatises on Chemistry : it is sufficient to notice the means by which it may be recognized, and its amount determined. Acetic acid may 86 ORGANIC CONSTITUENTS. be detected by its peculiar odoiir, whicb is rendered more obi-ious by the application of a gentle warmth. The presence of an acetate may be determined by the addition of a little sulphuric acid ; the odour of the liberated acetic acid is at once rendered perceptible. The addition of perchloride of iron to free acetic acid produces hardly any visible change, but if it be added to a solution of an acetate, a deep blood-red colour is produced. When acetates and free acetic acid are mixed up Avith a large quantity of other animal matters, the best method of proceeding is to separate the free acetic acid by distillation. The residue must be evaporated, extracted several times with alcohol, and the alcoholic residue mixed with a httle sulphuric acid, and distilled. The first distillation gives the free acetic acid, the second the acetic acid in a state of combination. The amount of acetic acid may be determined by satm'ating the distilled fluids with potash, evaporating to dmiess, and taking up the acetate of potash with alcohol of 'SSS. The acetate of potash obtained by the evaporation of the alcoholic solution is frequently mixed with a little chloride of sodium, the amount of which (if appreciable) may be determined by nitrate of silver. At a red heat the combinations of acetic acid with non- volatile bases are converted into carbonates. END OF INTRODUCTION. CHEMISTRY OF MAN. CHAPTEE I. ON THE PROXIMATE ANALYSIS OF COMPOUND ANIMAL SUBSTANCES. Zoochemical analyses are instituted for the purpose of ascer- taining, either quantitatively or qualitatively, the proximate or ultimate constituents of animal substances. It is requisite in physiological and pathological chemistry that equal attention should he paid to both these modes of investigation, for there is this great distinction between the chemistry of inorganic and of organic bodies, that in the former case the determination of the proximate principles can be inferred from that of the ulti- mate constituents, while in the latter case no such rule holds good, and the two species of analyses (the proximate and ulti- mate) must be conducted separately and distinctlJ^ In the in- vestigation of the variations in the constitution of the blood, whether dependent during health upon age, sex, or temperament, or during disease upon various pathological states of the system ; in the determination of the constituents of milk, sweat, or pus ; in the detection of sugar, urea, or bilin, in the various fluids, in which normally they are absent ; in these and all similar cases ultimate analysis will avail us nothing, and we must have re- course to tests for the substances themselves, or for some of their proximate principles. Investigations of this nature will, moreover, do very little for the advancement of pathological or physiological knowledge, unless they are -sdewed in relation to a considerable number of similar analyses, conducted under pre- cisely corresponding circumstances ; for in consequence of the necessary variation that is constantly occurring in the animal fluids, each analysis can only be regarded as the representative of 88 PROXIMATE ANALYSIS OF one of innumerable varieties, all of wliicli (within certain limits) are equally likely to occur. It is by sucli a course alone that we can hope to be able to deduce important and trustworthy con- clusions regarding the state of the animal fluids in health, and their various deviations from the normal standard, in different states of disease. A large number of perfectly distinct substances enter into the composition of the blood and urine ; neither of these fluids can, however, be regarded as true chemical combinations, but as mixtures of many such combinations, which in their turn are further subject to much variation. The study of these variations in the blood and mine constitutes one of the most important branches of animal chemistry ; but in consequence of the im- mense laboiu" attendant upon a complete analysis of these fluids, it becomes expedient to confine our attention to their most impor- tant constituents, in the same manner as the mineralogist seeks only to determine the proportion of ore in a given quantity of a mineral, or the vegetable analyst to ascertain the proportions of sugar, gum, starch, and albumen, while he neglects the non-nu- tritive substances, the fibre, acids, resins, colouring matters, &c. All compound animal substances that can fall within the range of our investigation must be embraced in one of the fol lowing classes, the solid, the fluid, or the gaseous. The animal fluids (to which we shall first devote our atten- tion) differ extremely in their composition, but a general scheme may be laid down for their investigation, if we pre\iously know that certain substances are not present, and thei'cfore need not be sought for. Thus, neither urea, uric acid, pepsin, nor bilin W'ill usually be sought for in the milk or in the brain, because it is well known that their formation is limited to certain organs ; neither will luematin, globulin, nor butyrin be looked for in the bile, nor fibrin in the sweat or in the saliva, nor glutin nor chondrin in any of the normal fluids. The principle upon which these investigations are conducted is dependent on certain questions, which are to be answered by the analysis. Thus in the analysis of the blood, the principal component parts, the water, albumen, hrematin, globulin and fibrin, are usually determined; but if it be requisite that the analysis should be more fully carried out, we must separate the hsBmatin from the globulin, isolate the fats, extractive matters, COMPOUND ANIMAL SUBSTANCES. 89 and salts, and determine their individual proportions. This is the plan that I have usually adopted, and in some cases I have added the determination of sugar, urea, and hsemaphain. The execution of such a comparatively simple scheme as this is a matter requiring considerable time and labour ; and if it were required that we should carry out the analysis still further, and separate the various fats, the different combinations of the ftitty acids, the varieties of extractive matter, and finally the different salts, our task, in the present state of our knowledge, would be one of great difficulty ; and in consequence of the minute pro- portions in which some of these substances exist in the blood, it would be necessary for us to operate upon a much larger quantity of the fluid than we are usually able to obtain. This method of investigation will probably in a short time be deemed insufficient, for as soon as we have an accurate knowledge of the mode of formation of the extractive matter, its separation and determination will be of the highest importance in explaining many of the phenomena of the metamorphoses of the blood. The same is the case with respect to the urine. The forma- tion of a perfect quantitative analysis of this complicated fluid is an extremely diflicult (if not an impossible) task, in conse- quence of the facility with which new products are developed during the progress of the investigation. The course usually pursued has been, therefore, the separation of those constituents which arc apparently most important, the urea, uric acid, salts, and extractive matter; in some cases the estimation of sugar and albumen has been added. The instances in which the se- paration of the extractive matter into its three principal groups, and the individual analysis of the salts, have been undertaken, are still more rare. It has been already observed that a single isolated analysis is of very little intrinsic value, in substances of so varying a na- ture as the blood or urine. The only method by which we can hope to throw any light upon the leading alterations that occur in these fluids is by the comparison of the results obtained from a series of analyses ; and if we were desirous of merely ascertaining so simple a fact as the determination of the pa- thological states in which either an excess or a deficiency of fibrin and blood-corpuscles occurs in the blood, and the relation that exists between such pathological states and such modifica- 90 PROXIMATE ANALYSIS OF tions of the vital fluid, science would be more benefited by the investigation, than by the performance of a few very perfect anatyses, which did not tend to elucidate any particular point. The best methods for the analysis of the various animal sub- stances Avhich are treated of in this volume, will be found in their proper places. We will, however, give a preliminary sketch of the course that should be adopted, if a fluid, of whose nature we are ignorant, be placed in our hands for analysis. Such a fluid may contain, I. The protein-combinations : fibrin, albumen, casein, glo- bidin.i II, Pyin. III, Extractive matters : water-extract, spirit-extract, alco- hol-extract, and their proximate constituents. IV. Sugars : Diabetic sugar, and sugar of milk, V. Bilin, with the products of its metamorphosis. VI. Urea. VII, l^he/ats: olein, stearin, margarin, butyrin, cholesterin, and serolin, VIII, Colouring matters : the pigments of the blood and bile, IX, The acids of the animal body : a. Fatty acids. j3. Other organic acids, y. Inorganic acids. X. The bases of the animal body. General physical analysis. 1, If the fluid contain flocculi or coagulated matters, they are generally composed of fibrin, which by its spontaneous coagulation frequently includes other substances in a state of mechanical suspension. The whole fluid will sometimes as- sume a gelatinous consistence, as has been observed in certain products of exudation; in other cases it presents an appearance of separation, one portion assuming the form of a cake or clot, whilst the remainder continues fluid, as in the well-known in- stance of the blood. On placing these clots, &c., in distilled ' Ciystallin, or the modification of casein that occurs in tlie crjstalhne lens, is not included in this scheme, since it is not known to occur in any of the animal fluids. ^ [I'vin being tritoxide of protein, must now be regarded as a true protein-com- jiound. The biiioxide of protein nmst also be included in the same category.] COMPOUND ANIMAL SUBSTANCES. 91 Avater, the substances wliich are inclosed by the fibrin gradually separate themselves from it, as for instance albumen, blood- corpuscles, &c., and the fibrin remains devoid of colour, very small in proportion to the clot from which it has been obtained, and forming a membranous, stringy, or flocculent mass. If the flmd has an acid reaction, the flocculi may arise from coagulated casein, or caseous substances. In this case dis- tilled water has no effect on them. The existence of casein in milk is universally known. Other fluids which contain caseous principles, as for instance, mucus and saliva, usually maintain an alkaline reaction for a considerable period, and thus hold the casein in solution. Pus has usually a neutral reaction, occasionally however pus from the lungs is acid. If the flocculi are observed to be floating on the surface of the fluid, if they exhibit a frothy appearance, or seem more or less globular, are of a whitish or yellow colour, and possessed of little tenacity, they are composed of mucus, and the micro- scope will reveal the presence of mucus-granules. A tenacious substance of a yellow or brownish colom', and not unfrequently containing blood, is occasionally foimd to be deposited in cer- tain animal fluids, for instance, in the urine during phthisis vesicce. It is possessed of more elasticity than mucus, and is verj^ probably composed partially of fibrin^ although it is usually regarded as pus. 2. If with the aid of the microscope we can detect blood- corpuscles in the fluid, we may infer the presence of globulin and hsematin. We recognize the blood-corpuscles, and dis- tinguish them from other objects by their discoid form, and their yellow colour. When blood is mixed with a serous or watery fluid, it frequently happens that the discoid form is no longer appai'ent ; if however a solution of common salt, or of mmiate of ammonia be added to a portion of the fluid, the characteristic shape of the blood-corpuscles wiU be again ren- dered perceptible. Fluids in which blood-corpuscles are found, are always of a reddish tinge, and invariably contain albumen. 3. The microscope further enables us to detect the follow- ing solid forms in fluids : a, fat-vesicles ; b, chyle-corpuscles ; c, mucus-corpuscles ; d, pus-corpuscles ; e, epithelium-cells ; /, saliva-corpuscles ; g, various crystalline forms of salts, uric acid, cholesteriu, &c. 92 PROXIMATE ANALYSIS OF If the fluid be very viscid and tenacious, mucus-corpuscles are sure to be detected by the microscope : should it yield an ammoniacal odour as if decomposition were going on, the viscidity may be due to the action of the ammonia that has been formed. 4. If the fluid have an acid reaction, a free acid must be present. In most cases this is lactic/ occasionally however acetic acid. The latter acid may be recognized by the pe- culiar odour evolved on the application of heat. It may also be recognized (if the fluid be not very deeply coloured) by the blood-red tint that is produced by the addition of the perchloride of iron, after the free acid has been thoroughly neutralized by ammonia. If acetic be the only free acid, by the time the fluid has been evaporated nearly to dryness, all acid reaction will have disappeared ; if however free lactic acid be present, the residue which is left after evaporation will still have an acid reaction. If the fluid have an alkaline reaction, either a free alkali or an alkaline carbonate must be present. Free ammonia may be recognized by its peculiar odour, and by the Vapour which is developed on the approximation of a glass rod moistened with hydrochloric acid. 5. If the fluid have a sweetish taste, it contains sugar. The sweetness is however sometimes not preceptible until the fluid has been evaporated to the consistence of a syrup, or even till the syrup has been treated with alcohol of -900, and the alcoholic solution evaporated. When the presence of sugar is suspected, the various tests mentioned in page 67, more especially Trommer's test, should be applied. If the fluid has a bitter taste, more or less resembling that of bile, it contains either bilin or the products of its metamorphosis. The indica- tions afi'orded by a well-marked saline or acid taste are sufficiently obvious. 6. If the fluid be of a blood-red colour, we may conclude that hsematin is present ; and if blood-corpuscles are detected by the microscope, we have certain proof of the existence of hsematin, globulin, and albumen. Globulin and hsematin may ' [The presence of this acid in the animal fluids has been recently disputed by Licbig and Enderling ; there are, however, too many chemists who assert that they have detected it, to allow us to regard the question as settled in the negative.] COMPOUND ANIMAL vSIIRSTANCES. 93 however be occasionally present, wlien, even after tlie addi- tion of a solution of salt, sugar, or iodine no blood-corpuscles can be detected; in this case the latter are in a state of perfect solution. When the fluid is of a dark brown, or blackish-red colour, haematin is the colouring constituent. If the fluid be of a clear brown or yellow colour, haemapheein is almost sure to be the origin of the tint, especially if any taste of bile be percep- tible. Biliphsein will also communicate a yellow, brown, or greenish-brown colour ; in this case there is frequently a bitter taste, and on the addition of nitric acid, there is always a change of colour into green or blue, and yellow. Qualitative analysis. Having poured the fluid into proper test-glasses, we carry on our investigations in the follo'svdng manner : 1. If, on the addition of very dilute hydrochloric acid, a precipitate be thrown down, we see whether it will dissolve in an excess of the test.' Assuming that the solution is efi'ected, ferrocyanide of potassium is added ; if this test instantly throws down a white or yellow precipitate, one or more of the protein- compounds (enumerated in i) are present. In order to ascertain which of the protein-compounds has yielded these indications,^ a portion of the fluid is boiled : if it become turbid, and if the turbidity commence and be most distinct at the surface, or if the fluid coagulate, then albumen is present ; in this case nitric acid and bichloride of mercury will throw down copious precipitates. If the fluid become turbid on the application of heat, and the coagulum assume a red tint, then globulin and hsematin are also present, although the microscope may have failed in detecting blood- corpuscles : in this case, however, the fluid is always of a rather pink or reddish tint. If the fluid does not coagulate on the application of heat, casein, or one of the caseous substances must be present. ' If very dilute hydrochloric acid he employed, the alhumen will not he precipi- tated. (See p. 18.) I prefer hydrochloric to acetic acid, because the latter throws down pyin with the protein-compounds. 2 Fibrin is recognized by its spontaneous separation, and need not be sought for in the manner indicated in the text. 94 PHOXIMATE ANALYSIS OF In this case heat will develop a pellicle on the surface, and acetic acid will throw down a precipitate, which is soluble in an excess of the test : the acid must therefore be added with caution. It must not however be forgotten that if much albuminate of soda, and at the same time no free albumen be present in the fluid, no coagulation will occur on the application of heat, but a pellicle will be formed on the surface. This is however a case of very rare occurrence, and the difficulty may be readily solved by the addition of acetic acid which will precipi- tate casein but not albumen. If a fluid which contains casein presents a whitish turbid appearance (as for instance, milk, the milky fluid which is found in the breasts during the later stages of pregnancy, the urine in certain pathological states, &c.) the presence of butter, and in most instances, of sugar, may be infeiTed. If the ferrocyanide of potassium does not produce any tur- bidity in the fluid which has been previously acidulated with dilute hydrochloric acid, no protein-compound is present. 2. If the addition of acetic acid to the fluid renders it turbid, or throws down a precipitate, which does not redissolve in an excess of the test, then pyin or mucini is present. In this case, a copious precipitate, insoluble in an excess of the test, is thrown down by alum. In order to show that the precipitate contains no casein, we may dissolve it in dilute hydrochloric acid, and add ferrocyanide of potassium : no pre- cipitate will be thrown down .2 3. If allantoin, uric acid, or hippuric acid are suspected to be present, a considerable quantity of the fluid must be boiled in order to coagulate any albumen that may be present, and must then be filtered and evaporated to one fourth of its original volume. Fluids of this nature are generally of a yellowish colour, may be either clear or turbid, and may or may not contain albumen. In the examination of the allantoic fluid, crystals of allan- toin are gradually formed, which, after being piu-ified by ' [Mucin is the peculiar animal matter of mucus ; a brief notion of its leading cha- racters is given in the chapter on the " Secretions of Mucous Membranes."] '■^ As chondrin and glutin are not constituents of any of the animal fluids, we have deemed it unnecessarv to notice them in the text. COMPOUND ANIMAL SUBSTANCES. 95 reciystallization, and dissolved in water, cannot be precipitated by acetate of lead, nitrate of silver, or nitrate of the black oxide of mercury. If the fluid, during evaporation, gives off an urinous odour some hydrochloric acid must be added, and it must be allowed to stand for some time. If acicular crystals are formed, which, after being purified by recrystallization, and dissolved in water containing enough alkali to neutralize the acid of the crystals, give a white precipitate with the above-named tests, an orange with the perchloride of iron, and when moistened with nitric acid, and warmed, do not assume a purple-red colour, they consist of hipimric acid. If however the crystals are very minute, are not readily dissolved in water, and give, when moistened with nitric acid and warmed, a purple-red stain, they are uric acid crystals. 4. If the fluid which we are examining is of a brownish yelloAV colour, and if on treating a little of it with an excess of nitric acid, the colour successively changes to green, blue and red, then biliphsein is present. 5. On evaporating a portion of the fluid to dryness, pulver- ising it, and boiling it with ether, we obtain, by the evaporation of the ethereal solution, a fatty residue. If it be fluid, it is composed of olein, if it have a tendency to be solid, either stearin or margarin, or both are also present. The fatty acids, and probably free lactic acid, with traces of other sub- stances may be present, especially if the ether contained any alcohol or water. These substances remain in solution, on washing the fatty residue with water. The lactic acid may be easily recognized by its acid reaction ; and the fatty acids may be detected by the addition of acetate of lead or acetate of copper to their alcoholic solutions. They are completely pre- cipitated in this manner, and a residue of pure fat is left, which must be again washed and the water removed by evaporation. The fat must then be saponified ; if a portion of it resists this process, cholesterin or serolin, or both, must constitute a por- tion of the fatty residue. They must be taken up by ether, after the saponified portion has been evaporated to dryness. Serolin is less soluble in alcohol, and melts at a lower tem- perature than cholesterin,' by which means the two fats may ' [Serolin melts at 95°, cholesterin at ahout 275°.] f)G PROXIMATE ANALYSIS OF be distinguished. The soaps which have been formed must be decomposed by hj-drochloric acid. If, on the addition of the acid; a smell of rancid butter is developed, then butyric, and also capric and caproic acids are present. The vari- ations in their melting points will enable us to determine approximately the proportions of oleic, margaric, and stearic acids. 6. The residue not taken up by ether, must be treated with anhydrous alcohol, which will take up the following substances : salts of the fatty acids, especially soda-salts, as well as any fat that had escaped the action of the ether, also urea, bilin and the acids of the bile, biliverdin, alcohol- extract, hsemaphsein, acetates, and lactates, a class of substances which it is by no means easy to distinguish, and is still more difficult to isolate. If a spirituous solution of chloride of barium be added to the alcoholic solution, and a green precipi- tate is thrown down, then biliverdin is present ; we may also calculate with tolerable certainty (especially if the alcoholic solution has a bitter, bilious taste) on the presence of bilin, and the acids of the bile. An alcoholic solution of sulphuric acid must now be added to the alcohol-solution that we are testing, as long as any sulphates are precipitated. The solution must now be filtered, and the alcohol, which still has an acid reaction if any acetates are present, must be removed by dis- tillation. On treating the residue with water, the fatty acids, if they existed in combination with saline bases, will remain imdissolved, and must be removed by filtration. A portion of this watery solution must be evaporated to the consistence of a syrup, and allowed to cool; if, on the addition of an excess of nitric acid, there are formed, either at once or after some time, leafy or stellar crystalline groups, then urea is present. Another portion must be treated with dilute sul- phuric acid, and allowed to digest for some time. If bilin, and the products of its metamorphosis, are present, a viscid or oily acid, (insoluble in the acid fluid,) and a precipitate of an extremely unpleasant bitter taste, are formed. The fluid sepa- rated from these substances must be digested with pounded marble, or (which is better) with carbonate of baryta, in order to remove the sulphuric acid. It must then be boiled with carbonate of zinc ; if it contain lactic acid, crystals of lactate COMPOUND ANIMAL SUBSTANCES. 97 of zinc will be obtained ])y evaporation. The extractive matter and haemaphsein will be left as a residue. If neither bilin, biliverdin, nor the acids of the bile are pre- sent, the investigation may be much simplified. The soda may be separated from the alcoholic solution as a sulphate ; we may evaporate, separate the fatty acids by means of water, boil the residue with carbonate of zinc, and filter the solution. By this means we can separate the lactic acid. The urea may be se- parated from the alcohol-extract by oxalic acid, of which any excess may be removed by digestion with carbonate of lead. We may be easily conAdnced of the presence of the alcohol- extract by observing the precipitates which are thrown down by the addition of infusion of galls and a solution of iodine. The bases, which were present in the alcoholic solution in combination with acids, are now combined with sulphuric acid. They usually are soda and potash. 7. The residue of (6), which was not taken up by absolute alcohol, must now be treated with alcohol of -883, which will take up sugar of milk, diabetic sugar, spirit-extract (which is usually of a brown colour in consequence of the presence of hsemaphaein,) chloride of sodium, phosphates, and probably lac- tates. If the quantity of sugar (of either of the above kinds) is not very minute, a portion of it Avill usually crj^stallize either on the cooling of the spirituous solution or by spontaneous evaporation. The presence of the sugar may, however, be easily recognized by the sweet taste of the spirituous solution after evaporation. If the solution be evaporated to the consistence of an extract, and then treated with cold alcohol of -850, the greater part of the sugar will remain undissolved, while most of the extractive matter will be taken up. The presence of the extractive matter may be determined partly by the brown colour of the spirituous solution, and more decidedly by the precipi- tates which are caused by the addition of bichloride of mercury, acetate of copper, and tannin. The spirit-extract usually evolves during evaporation a peculiar odour, somewhat resembling that of toasted bread. On evaporating a portion of the spirituous solution to dryness, and incinerating the residue, the ash will be found to consist of chloride of sodium, phosphates, and (if any lactates are present) carbonates of potash and soda. These may be separated in the ordinary manner. 7 98 PROXIMATE ANALYSIS OF 8. The residue not acted on by alcohol of '850 must be dissolved in Avater, in Avhich, if no protein-compounds are present^ it will dissolve without leaving a residue, although the solution may not be clear. In this solution there will be con- tained pyin, ptyalin, water-extract, phosphates, and perhaps some chloride of sodium. The pyin is recognized by the precipitate afforded by acetic acid. The ptyalin, when it is present only in small quantities, and is mixed with extractive matter, is not easily detected ; the only course we can adopt is to precipitate the whole of the extractive matter of the water-extract with the basic acetate of lead. A stream of sul- phviretted hydrogen must then be passed through the fluid in order to precipitate the lead. The liquid, after filtration or decantation, must be evaporated to the consistence of a syrup, and the ptyalin precipitated by alcohol. I may here remark that, in pursuing the directions laid down in (7), we do not succeed in obtaining all the spirit- extract that exists in the residue of (6). Hence in practice it is better to dissolve the residue of (6) in a little water, so as to reduce it to the consistence of a syrup, and then to precipitate with alcohol of 'SSS. The salts may be obtained by incinerat- ing a portion of the evaporated fluid. In the last six paragraphs we have assumed that no protein- compounds are present. If, however, this should not be the case, — if some of the constituents of the blood, as, for instance, globulin or haimatin, exist in the fluid, a different course must be pursued. The presence of globulin and hsematin, and, con- sequently, of albumen, may be easily ascertained. The fluid must be boiled, evaporated on the water-bath to dryness, and the residue reduced to a fine powder. The fat must be taken up with ether, and the urea, alcohol-extract, bilin, with its acids, and any htemaphrein and lactates that may be present, with anhydrous alcohol. The residue must be boiled in spirit of "915 until it ceases to communicate any additional red colour- ing matter to that fluid. In this way Ave shall obtain the globulin, hsematin, haemaphsein, sugar, extractive matters, and several salts, in a state of solution. The greater portion of the globulin and lipematin is thrown down as the fluid cools ; the turbid supernatant fluid is then evaporated on the water-bath to a small residue, and treated Avith alcohol, Avhich precipitates COMPOUND ANIMAL SUBSTANCES. 99 the remaining portion of tliose two constitnents. Other sub- stances are contained in tlie spirituous solution, which may be distinguished and separated by the rules already given. The residue not taken up by the alcohol of -915 must be treated for some time with water, by which pyin, ptyalin, and water-extract will be taken up. The albumen remains as a residue, usually more or less reddened by a little hjematin. If the fluid be very rich in albumen, this course does not succeed, inasmuch as we are unable to obtain a complete sepa- tiou of those substances which are soluble in dilute alcohol, as sugar, urea, salts, and extractive matters. The following simple modification may in that case be adopted. The protein-com- pounds must be precipitated by anhydrous alcohol. A spiritu- ous solution is thus obtained, which, even when concentrated, holds the urea, sugar, &c., in solution, while the protein-com- pounds (at least the albumen) are reduced to an insoluble con- dition. The coagulated protein-compounds are always mixed up with a certain amount of foreign matters, as, for instance, water-extract, which cannot be easily separated. After the removal of the albumen, &c., the spirituous solution must be evaporated to the consistence of a syrup. On the addition of anhydi'ous alcohol, sugar, spirit -extract, any albumen that had escaped the former process, and some other substances, will be precipitated. The alcoholic solution must be evaporated, and the residue dissolved in water, by which means the fat will se- parate itself. The fat is, however, difficult to remove, in con- sequence of the slow and torpid manner in which the fluid permeates the filter. It is better, therefore, to evaporate the alcoholic solution, at a very gentle temperature, to dryness, and then to take up the fat with pure ether. In searching for minute quantities of urea in alcoholic solu- tions of concentrated animal fluids, it frequently happens that, after evaporation of the alcohol, the removal of the fat, and the solution of the residue in water, the action of nitric acid on the urea is much impeded by the presence of compounds of the fatty acids. I therefore usually remove the bases from the alcoholic solution by means of sulphuric acid, which liberates the fatty acids, and allows of their removal with the fat by means of ether. The sulphuric acid should be much diluted with strong alcohol; and as it is of importance that there 100 CIRCULATING FLUIDS: be no excess of tlie acid, it must be added guttatim, and only so long as it produces a precipitate, wliicli sometimes is not observed for several hours after the addition of the acid. The effect of the sulphuric acid should first be tried on a small portion of the fluid. If it is difficult to lay down general rules for the quali- tative analysis of all the proximate constituents that can by any possibility occur in the fluids of the animal body, it may easily be conceived that an attempt to lay down similar rules for quantitative analysis would involve much greater diffi- culties. Such a general quantitative scheme is, how^ever, not required, since quantitative analyses are always preceded by, and based on, qualitative investigations. The fluids most troublesome to analyse are the blood and the urine, on ac- count of the large number of different substances that always occur in them. The rules for the quantitative analysis of the various fluids will be found in the respective chapters on the blood, milk, urine, &c. CHAPTER II. THE CIRCULATING FLUIDS. The Blood. The following scheme will explain the arrangement which we have adopted for the general consideration of the blood. 1. The General Physiological Chemistry of the Blood. Its general physiological and chemical relations; the deve- lopment of the blood-corpuscles ; the phenomena of circulation and respiration ; the metamorphosis of the blood, and animal heat. 2. The Special Chemistry of the Blood. The method of analysing the blood. Healthy blood. Diseased blood. BLOOD. 101 1 . The general physiological chemistry of the blood. General physical relations of the blood. The bloody while moving in the living body, consists princi- pally of a nearly coloiu-less fluid, in which the blood-corpuscles are swimming ; in consequence, however, of these coi'puscles being too minute to be distinguished by the naked eye, it appears, among the higher classes of animals, as an opaque and intensely red fluid. In the majority of the lower (invertebrate) animals, the blood is white ; it is however red in the annelida, colourless in most of the mollusca, but in many of the snails of a milk-white colour; in the Helix pomatia of a sky-blue, and in the Pla- norbis corneus, of a dark amethyst colom*. In the dorsal vessels of insects it is usually transparent, and of different colours ; it is, for instance, green in the Orthoptera, yeUow in the silkworm, orange in the caterpillar of the willow-moth, and of a dark brown colour in most of the beetles. i The blood-corpuscles of red blood contain within their coat, or shell, a fluid impregnated with globulin and haematin, and a nucleus, which may be easily recognized in the larger cor- puscles. The blood of the mammalia is a somewhat thick, viscid fluid, with a specific gra\ity which varies, according to dif- ferent authors, from 1041 to 1082. In a large number of experiments made upon the blood of man, the ox, and the horse, I found it to be between 1051 and 1058. The average was 1042, which corresponds very nearly with the statement of Berzelius. [The average specific gravity of human blood may be fixed at 1055 according to Nasse,^ and at 1056 according to Zim- mermann.^ The blood of man is always thicker, and at least one thousandth hearier than that of woman ; in a state of health it is always above 1053 in man, while in woman it is frequently not above 1050. Robust men will not unfre- quently yield blood of spec. grav. 1058 or even 1059, Avhile in pregnant women the specific gravity is sometimes as low as ' Burdach's Physiologie. 2 Ai-ticle ' Blut,' in Wagner's Ilaiuhvorterbiich, vol. 1, \). 82. ' Hufeland's Journal, 1843. 102 CIRCULATING FLUIDS: 1045. In very young infants the blood is thin, and of low specific gravity ; according to Denis the blood of the umbilical arteries has a specific gravity of 1075. The specific gravity of the blood of numerous animals has been determined by Dr. J. Dav\'i and by Nasse.] I found that the blood, as it issues from the aorta, has a temperature of 103° in the ox, and 99° -5 in the pig. Thackray places the temperature of the blood of the horse at 96°-8, of the ox at 99' -5, of the sheep at 101 ''•3, and of the duck at 105°'8. The temperature is always higher in birds than in the mammalia. The observations of J. Davy, Becquerel, Breschet, Mayer, and Saissy, tend to show that the temperature of arterial is about 1°'8 higher than that of venous blood. Microscopic analysis of the blood. If the blood be examined with the microscope (either in a transparent living part, or immediately after its removal from the bod}'), it will be seen to consist of a great number of yellow corpuscles swimming in a colourless fluid. In the higher animals the form of these corpuscles is either circular or elliptic, and invariably flattened. Under a magnifying power of 300 diameters, they assume the appearance of fig. la in the blood of man and the mam- malia, of fig. 1 Z» in the blood of birds, and of fig. 1 c in the blood of fishes and amphibia. Mviller ' found the greatest degree of flattening in reptiles, amphibia, and fishes. He found that in frogs the thickness does not measure more than one eighth to one tenth of the long diameter, and that in man it measures about one fourth or one fifth of the transverse diameter. In addition to the blood-corpuscles, lymph-, chyle-, and sometimes oil-globules are present. The first two are round, of a finely granular appearance, and about the size of the blood-corpuscles, from Avhich they may be distinguished by their want of colour, their more perfect sphericity, and their granular appearance. ' Anatomical and Physiological Researches, p. 24. ^ Ilaiidbuch dcr Physiologic dcs Meuschcii, vol. 1, p. 105. BLOOD. 103 These distinctions are sufficient to prevent them from being mistaken for blood-globules. Globules of oil may be immediately recognized by their well-defined dark edge, and by their great refractive power. They do not rotate, and are not granular, but perfectly transparent. The size of the blood-corpuscles vai'ies in different animals. In man, the diameter varies, according to Wagner,^ from •0004 to •0002 of a French inch ; according to Miiller,- from •00035 to -00023, and according to Schultz', from -00036 to -00031. The thickness, according to the last observer, may be estimated at -000085 of the same measure. Of all the mammalia, the iniminants seem to possess the smallest blood- globules, Wagner has given the following proportions : In man and monkeys -j^^.th of a line = 3. Carnivora . . ^ih. of a line = 4. Kuminantia . ji^^th of a line = 5. In addition to these admeasurements, the following m^e de- sening of notice : Xasse fixed their average diameter at -00033, the maxima and minima being '00036 and -0003 ; Bowerbank places their average diameter at from -00035 to •00027, the extreme limits being -00054 and ^00021 respectively ; Owen at ^00028 ; and Gulliver at -0003 of an inch. The dimensions of the blood-corpuscles in the foIlo-\\'ing animals have been measiu'ed : Ape (Simia callitrix) -00037^ (Prevost and Dumas). Cat -00028; dog -00031 (Sclmltz) ; rat and mouse about -00025 (^^agner). Sheep -0002 (Schultz and Wagner) ; ox -0002 (Schultz) and -00024 (Wagner); goat -00017; chamois -0002 (Prevost and Dimias); horse -00031 — -00027 (Schultz). According to Wag- ner, the diameter in rats, mice, hares, and squirrels, varies from -00025 to -00020. The blood-corpuscles of birds, fishes, and amphibia are el- liptical. The following are the results of some of the best authenticated measurements : Common fowl : length -00062 ; breadth -00036 ; thickness •00013 (Schultz). According to Dumas and Prevost, the long ' Nachtrage zur Physiologic des Blutes, 1838, p. j. - Physiologic des Menschcn, vol. 1. p. 106. ■' System der Ciikulation, p. 14. ^ French inches. 104 CIRCULATING FLUIDS: diameter in the pigeon, duck, and goose, varies from -0008 to •00044 ; the short diameter from -0004 to -00029. Wagner estimates the two diameters, in the pigeon, at "0008 and "00033 respectively. "VVe find the largest blood- corpuscles in fishes. According to Wagner' the largest corpuscles, at present observed, are those of the torpedo, their long diameter being '002 ; in the skate he found them to vary from -001 to '0012 in length; in the loach the long diameter was "0005 ; in the eel-pout, 00057 ; in the barbel -00066, the short diameter in this case being -0004. In the carp the long diameter is -0005, and the nucleus measures -00012. In the plaice, Schultz estimated the long and short diameters at -00062, and -00043 respectively, and the thickness at -00007. In the naked amphibia the corpuscles are very large. In the triton, Dumas and Prevost estimated the diameters at •00128 and -00078 respectively. In the Salamandra cristata, Schultz found that the diameters were -00138 and -000804 and that the thickness was ^000315. In the frog, the same observer estimated the length, breadth, and thickness at •OOIOS, and -00058, and -000017. Of all the amphibia, the water-snakes appear to possess the smallest blood-corpuscles. 2 The instantaneous effect of water upon the blood-corpuscles is very remarkable, and is easily seen under the microscope : they swell, become globular, lose their distinct contour, and (if much water be added,) altogether disappear. If however the blood-corpuscles have nuclei of sufficient magnitude to admit of examination (as in the blood of fishes, reptiles, &c.), these nuclei Avill be seen swimming in the water after the disappear- ance of the capsules. The nuclei may be separated in a similar manner, by the addition of a little acetic acid. The acid in a few minutes dissolves the hamato-globulin, and assumes a yellow colour. ' Zur vergleichciulen Physiologic ties Blutes, 1833, p. 14. [The largest blood- corpuscles do not occur in fishes, as stated in the text, but in some of the naked am- phibia. See Wagner's Physiology, p. 236, English edition.] ' A very complete account of the sizes of the blood-corpuscles of different animals, as far as they had been then ascertained, may be found in Wagner's Nachtrjige zur Physiologic des Blutes, 1839, p. 31. BLOOD. 105 If, upon the addition of water, the blood-corpuscles have swelled to such a degree as to be imperceptible under the mi- croscope, they may be restored to their pristine form by the addition of a solution of sugar, of common salt, of nitrate of potash, or of muriate of ammonia. Schultz^ explains this phenomenon by the supposition that the capsule of the blood- corpuscle is an organic structiu"e, which is stimulated to con- traction by the above solutions, but which is relaxed or ex- panded by water. In confirmation of this view, he observes that the haemato-globulin is not precipitated by the action of the sugar or salts. Schultz has also shown that when the capsules have even fallen to pieces in the water, the addition of a little tincture of iodine, diluted with water, will render their fragments 'sdsible. The blood-corpuscles do not always present a regular num- mular and flattened appearance ; they are sometimes plicated and bent in. The cause of this phenomenon is not known, but it is pro- bably due to a contraction of the capsule at different points. One of the most peculiar of these forms is that in which the edge of the blood-corpuscle appears as if it were studded with minute pearls. In the blood of a patient suffering from Bright's disease, I found that nearly all the corpuscles had undergone this modification. On the addition of a solution of muriate of ammonia, the appearance it presented under the microscope was very striking. I immediately made a counter- experiment with my own blood, but it did not exhibit the phenomenon in question. Ascherson''^ has offered the following explanation of this peculiarity in the form of the corpuscle, viz., that it is due to the exudation of fat which exists in a fluid state in the blood- corpuscle. In opposition to this view, it may be urged, that if each individual corpuscle contained a separable portion of fat (how- ever minute it might be), we should obtain in our analyses a much larger quantity of fat than in reality we do. It is true that the dried clot yields a larger proportion of fat than an equal ' Ueber die gehemmte und gesteigerte Auflosung der verbrauchten Blutbliischen. Hufeland's Journal, April 1838, p. 18. ^ Miiller's Archiv, 1840. Uebcr die Bedeutung der Fettstoffe. 106 CIRCULATING FLUIDS: weight of serum^ but tlie difference is by no means so striking as it would have been if Ascherson's theory were correct. Hiinefeld ^ has obsei'ved a similar appearance on treating the blood-coi'puscles of the frog with putrid serum, in which granules were present. The granules seemed to form a sort of girdle round the corpuscle, and he conceives that they penetrated into minute depressions upon the surface of the capsule. If this statement be correct, it is strongly opposed to the observations of Ascherson and Wagner respectmg the lubricity and evenness of the blood-corpuscles. On mixing the blood of a cai-p with a solution of sugar, and on the cautious addition of water, I observed that the blood-corpuscles assumed a stellar appearance. On treating frog's blood Avith bilin, an agent which usually dissolves the corpuscles, I observed that some of them resisted this action for a considerable period, and ultimately assumed a pyriform appearance, while otlicrs became narrowed at the centre, and extended at both extremities. Others, again, seemed to undergo an internal change, and appeared as if their inner surface were studded Avith minute vesicles. Hiinefeld made a similar observation on treating frog's blood with carbonate of ammonia. ^ The same chemist observed a remarkable peculiarity in the corpuscles of human blood, on the addition of sulphate of quinine. In the course of a few minutes they assumed an in'egular, angular form, and appeared as if their sides were drawn together. Schultz^ has made the following important microscopic ob- servation. On examining the blood-corpuscles of a salaman- der which had been suffocated in carbonic acid gas, they were found to be of a darker colour than usual ; the darkness was particularly marked on some spots, so that they exhibited a sort of chequered appearance. On shaking the blood with oxygen gas, the corpuscles be- came brighter and more transparent. ' Der Chemisums in iler thierischen Organisation, p. 101. 2 L. c, p. 106. •> System dor Cirkulation, p. 27. BLOOD. 107 A. The general chemical relations of the blood. The general chemical relations of the blood-corpuscles. Miiller and Schultz have examined the action of various tests on the blood-corpuscles. Hiinefeld' has also recently paid much attention to the apparent effect produced on them by numerous medicinal agents. According to the last-named author, the corpuscles and their nuclei are soluble in the fol- lowing substances : caustic ammonia, potash, soda, lime, and baryta, soap, bile, acetic acid, hydrocyanic acid, alcohol, ether, oil of turpentine, ethereal oil, and sulphm'et of carbon. The capsules, but not the nuclei, are soluble in water, in all the salts of ammonia, the carbonates of potash and soda, cyanate of potash, borax, chloride of barium, chloride of calcium, the salts of oxalic and hydrochloric acids, concentrated \inegar, and the phosphoric, arsenic, oxalic, citric, and hydrochloric acids. Phosphorus, chlorine, and iodine produce a similar effect, probably by the formation of an acid. An imperfect solution is effected by flowers of sulphur, tartrate of ammonia, borate of ammonia, bromide of potassium, and malic acid. The corpuscles are not dissolved by carbonate of magnesia, ve- ratrine, strychnine, acetate of morphine, hydrochlorateof coneine, boracic acid, carbonic acid, nitrate of potash, nitrate of soda, tartrate of soda, phosphate of soda, chloride of sodium, sugar, gum, sulphate of potash, sulphate of magnesia, sulphate of soda, tartar emetic, camphor, anemonine. Hiinefeld also tried the eftects of several of the animal fluids on the blood. Saliva, phthisical sputa, and healthy pus pro- duced no well-marked changes. Gastric juice, added to an excess of blood, induced a slight coagulation, and changed the red colom* into a brown. The extractive matter of the flesh of rabbits and calves produced no change on the corpuscles, but the colour assumed a more vermilion tint, and the corpuscles sank sooner than usual. Acid whey, concentrated by evapo- ration, produced no efl"ect, neither did the pancreatic juice or gonorrhoeal discharge. Sweat, taken from the axilla, changed the colom- to a lighter red, and, in the course of some hours, ' Der Cheiuisiuub, u. s. w., p. 43-84. 108 CIRCULATING FLUIDS: dissolved the corpuscles, (possibly through the influence of the ammoniacal salts.) Pure urea, prepared artificially, induced no change in the colour, but dissolved the corpuscles, with the exception of the nuclei and a few fragments of the capsules. The action of putrid blood and serum has been already noticed. Human blood does not appear to be influenced by admixture with the blood of birds or frogs. The bile of man, quadrupeds, birds, fishes, and amphibia, exerts an active soluble influence upon the corpuscles. In some observations on frog's blood, Hiinefeld noticed that the capsules were immediately dissolved, and that the nuclei re- mained unchanged for some time, but ultimately broke up into minute granules and disappeared. The effects produced by coneia appear, from Hiiuefeld's ob- servation, to be very singular. Coneine, either in a state of solution or vapour, reduces the blood to a dirty red greasy mass, which, under the microscope, resembles dark melted wax, and in which no corpuscles can be detected. If diluted blood be treated with a little coneine, it remains fluid, but, after a short time, becomes discoloured, and throws down a brown sediment. The blood of a rabbit, poi- soned with coneine, exhibited no peculiarity. Arsenic acid produces no material eftect upon the blood, nor could Hiinefeld detect any alteration in the corpuscles of a frog destroyed by this agent. On passing hydrocyanic acid, in a state of vapour, into the blood of a pig, the colour became more vivid, and the corpuscles remained uninjured for a very considerable time. A large quantity of blood, which was treated in a similar manner, gave off a strong odour of the acid after the lapse of a year and a half, and did not exhibit any symptoms of putrefaction. No change could be observed in the blood of a rabbit poisoned with this agent. Chlorate of potash does not produce any apparent effect for the first few minutes ; subsequently, however, the blood assumes a brighter red tint, which ultimately passes into a brown. An ounce of fresh human blood Avas mixed Avitli eight grains of chlorate of potash. Just at first the colour became rather BLOOD. 109 brighter, but, after tlie lapse of from fifteen minutes to an hour, it became darker than it previously was. It then became of a reddish brown colour, and, after from eight to sixteen hours, it was converted into a pulpy brownish-black matter. The blood of a cat which had taken a drachm of this salt, and had afterwards been killed with cyanogen, exhibited no peculiar appearance. Hiinefeld, and some other microscopists, assert that acetic acid dissolves the whole of the corpuscle, with the exception of the nucleus. Miiller, on the contrary, maintains that in frog^s blood the colouring envelope is not wholly dissolved, but may still be frequently observed in a pale fine line surround- ing the nucleus. The following are my own observations with respect to this test. If a sufficient quantity of acetic acid be added to freshly drawn blood, so as to give it a decidedly acid reaction, and if the vessel in which it is contained be submitted to a temperature of about 88^ for half an hour, the blood becomes changed into a thick tar-like mass of a blackish brown colour. If water be now added, and the mixture carefully stirred until it is reduced to a magma of an equal consistence through- out, we find that, on examining a portion of this mixtiu-e under the microscope, the addition of some more water does not dis- solve the corpuscles ; in fact, they are no longer soluble in water, in consequence of the insoluble compound that has been formed by the acetic acid, and the (casein-like) globulin. If a great excess of water be added, the corpuscles sink; the albumen, and a great portion of the hsematin, which enter into their composition, are dissolved, and they become almost per- fectly clear. They may even be boiled in water, without any change in their form being produced. When boiled in acetic acid (unless it be very dilute), they become perfectly dissolved, with the exception of their nuclei.^ According to Miiller and Schultz, a solution of caustic am- monia dissolves the corpuscles more rapidly than a similar solution of caustic potash. The same observers state that alcohol does not dissolve them, but merely produces a shght contraction or puckering, and that the granules of albumen ' F. Simon's Beitnlge zur Kenntniss desBlutes, in Brandes's Archiv, vol. 18, p. 3o. 110 CIRCULATING FLUIDS : coagulated by this reagent cloud the field of vision, and render the corpuscles indistinct. I have also found that neither abso- lute alcohol, nor alcohol of 'SSo, effect the solution of the cor- puscles. It has been found by Schultz, Hiinefeld, and myself, that the blood-corpuscles dissolve upon the addition of a small quan- tity of ether. A quantity corresponding in volume to from one third to one half of the blood is perfectly sufficient. This experiment has been successfully repeated upon the blood of man, the ox, the frog, and the carp. If the experiment be performed in a test-glass, it will be obsen-ed that the colour of the blood very soon becomes deep- ened, but that ultimately the whole fluid becomes transparent. The ether does not separate during this process. If a portion of this mixture be covered with a slip of thin glass, and examined under the microscope, no corpuscles, but simply the nuclei, are discernible. The nuclei in the blood of man and the ox cannot be clearly seen on account of the colour- ing matter that is always present ; they may, however, be always distinctly observed in the blood of the frog or the carp for a considerable time. A mixtui'e of ether and blood, kept in a stoppered vessel for some time, became thick, assumed a greasy appearance, and was no longer fit for the experiment ; neither could a satis- factory result be obtained on shaking blood with an excess of ether ; for then the ether took up the water of the blood, and thus reduced that fluid to a state of thickness. On pouring off the ether from a known quantity of blood with which it had been continuously stirred for twent^'-four hours, and submitting the blood to a single washing with ether, I was astonished to find that fi'om the two ethereal solutions I obtained quite as large a quantity of fat as I should have done by the repeated extraction of a corresponding portion of dried and finely-powdered blood with boiling ether. On treating pure liquid serum of the same blood in a similar manner, the quantity of fat obtained did not differ from the quantity obtained from the perfect blood, in a ratio sufficient to justify the supposition, that the capsules are composed of fat. I can also confirm Hiinefeld's observation respecting the influence of bile upon the blood. On the addition of fresh bile, BLOOD. Ill the blood immediately becomes clear, and the corpuscles dis- appear. In consequence of the viscidity of ordinary bile, I experimented with pure bilin. Upon the addition of a Httle partially dried bilin to the blood of man, the calf, the tench, or the frog, the fluid becomes, after a little stirring, thick, almost gelatinous, capable of being drawn out into threads, and no corpuscles can be seen in it. If a minute drop of frog's blood, in which the corpuscles have been thus dissolved, be brought in contact, and suffered to mix with a fresh drop of blood from the same animal, an interesting microscopic object is afforded. After the first intense action is over, the corpuscles are seen to move about slowly, or to be in a state of rest, and gradually to disappear. The solution of the capsule (not of the nucleus) occurs so instantaneously that the eye cannot trace the reaction. The nucleus always remains as a granular mulberry-like corpuscle. It becomes gradually paler and paler, enlarging itself visibly at the same time, and at last its existence can only be ascertained by its brightness. I have never succeeded in observing the decomposition of the nucleus into its constituent parts, which has been described by Hiinefeld, although I have carefully repeated his experiments. I usually obseiTcd, however, that at those points where many corpuscles had disappeared, numerous minute points were visible, of which the larger ones displayed a lively molecular motion. In those instances in which the corpuscles resisted the solvent power of the bilin for a considerable time (possibly in consequence of the reagent being applied in too dilute a state), they often as- sumed very peculiar forms ; appearing as if they were twisted, and extended longitudinally in one direction, or variously colom-ed in the interior. (Vide supra, p. 106.) I have formerly noticed the solvent power of olive oil upon the corpuscles.! I shook a quantity of the blood of a calf, which had been allowed to flow from the vein into a vessel one quarter full of olive oil, until the blood was perfectly cool. No cor- puscles could then be detected. Whipt blood exhibits the same phenomenon; but in this case it is requisite that the oil should remain for a longer period in contact with the blood. This fact has also been noticed by Magendie.'^ • Pharmaceutisches Ceiitralblatt, 1839, p. G72. * Lemons sur le Sang, et les alterations dc cet liquide, par Magendie. Bruxelles, 1839. p. 244. 112 CIRCULATING FLUIDS: B. The general chemical relations of the colouring matter of the blood [Hcematin.) The red colouring matter of the blood is contained^ in all probability^ in a state of solution in the corpuscles, an opinion which is also supported by Midler, Schultz, and Reichert. If, in the examination of frog's blood, one corpuscle be observed to move over another, the lower can be distinctly perceived through the upper one. Moreover, the instantaneous solution of the corpuscles by means of bilin supports this \iew ; for, if their contents were gelatinous or solid, the act of solution would be observed to progress from the circumference to the centre, and would admit of being observed by the microscope. Hiinefeld^ seems to support the opinion that the colouring matter exists in an insoluble form, attached to the inner surface of the capsules. If, however, this were the case, the blood- corpuscles would appear more opaque than they do. The observations of Hiinefeld and others show that the follow- ing substances heighten the red colour of the blood : cold water-extract of the flesh of rabbits and calves (having an acid reaction) communicates a vermilion colour to the blood. It becomes of a deep garnet red by the carbonate, cyanate, and nitrate of ammonia, and less intensely by the saliva, phthisical sputa, gonorrhoeal matter, sweat, hydrocyanic acid, the carbo- nates of soda and potash, and bicarbonate of soda. A brown tinge may be produced by the agency of several substances; for instance, by all free acids, by sugar of milk, oil of bitter almonds, ammonia, boracic acid, carbonate of mag- nesia, tartrate of potash, bromide of potassium, sulphate of magnesia, chloride of strontium, nitrate of strontia, lactate of iron, phosphorus, iodine, &c. The alkalies, alkaline earths, and sulphuret of potassium produce a green tint. It becomes entirely decolorized by the action of coneine and oil of turpentine. c. The general chemical relations of the nuclei of the blood-corpuscles. The similarity of the constitution of the nuclei to coagulated fibrin has been long observed. Hiinefeld,^ however, conceives ' L. c, p. 104. ' Der Chemismus, u. s. w., p. 108. BLOOD. 113 that corpuscles, instead of consisting of fibrin, are mainly- composed of fatty matter (either cholesterin or some allied substance), combined with allnimen, as occurs in the yelk of eggs. In this view I cannot coincide, although I fully believe that albumen and fat do take a very active part in the formation of all the animal tissues, and, consequently, in the production of the blood- corpuscles. In this instance, the formative process has advanced so far that we can expect to find the original materials of formation present in only very small quantities. It is true that the fibrin and the blood- corpuscles contain a greater relative proportion of fat than the other constituents of the blood ; yet even in fibrin the propor- tion amounts to only 5^, and the fat cannot therefore be re- garded as a preponderating constituent of this substance. That the fat is not actually cholesterin seems pretty clear from the fact of the ready solubility of the corpuscles in caustic potash. The diameter of the nucleus is usually about one-fourth or one-fifth of the diameter of the blood-corpuscle. In the amphibia it varies from "002 to "005 ; in fishes, from •0016 to •0025 ; in birds, its length is about '002, and in the mammalia •0008 of a line. I have made the following observations with regard to the nuclei in the blood of man,^ the carp, and the frog. The nuclei in the frog appear, after the solution of the capsule and lipemato-globulin, as partly elliptical and partly cylindrical. After washing them for a day or two in order to remove the colouring matter and albumen, they assume a more spherical form, and most of them present a granidated appearance on the surface. I cannot, however, positively assert that granular cells were present, nor did I observe the nuclei separate into distinct portions during this treatment. The nuclei, even when moist, were not soluble in boiling ether. When dried, moistened with water, and then observed under the micro- scope, several nuclei were seen floating about, apparently un- altered; many were, however, connected together in such a manner as to prevent their whole outline from being apparent. Upon treating the dry nuclei with ether, appearances similar ' I allude to the nearly colourless sediment which may be obtained by washing blood with a large quantity of water, and which is found to contain lymph-corpuscles and fragments of capsules. 8 114 CIRCULATING FLUIDS: to those abeady described were perceived. Moist nuclei dis- solved readily in caustic potash -, if the solution be supersatu- rated with concentrated acetic acid, and heated, an imperfect solution of the matter, precipitated by the acid, occurs ; a very small quantity of dilute hydrochloric acid will, however, readily dissolve the whole. On treating the filtered solution with tannin, a copious precipitate was thrown down; ferrocyanide of potassium caused a mere turbidity, or very sHght deposit. Similar observations were made on the nuclei of carp's blood, but the ferrocyanide of potassium caused less turbidity than in the former case. The nuclei of human blood are scarcely dis- cernible in the viscid sediment. The effect of reagents was much the same as in the former cases. Hence we are led to infer that the l:)lood-corpuscles are chiefly formed of a substance closely related to the protein- compounds, although not identical with any of them : possibly the nuclei may be converted into fibrin, soluble in the liquor sanguinis, after the metamorphosis of the blood-corpuscles has been accomplished. On heating the nuclei on platina foil, a fatty smell is first observed, and then an odour resembling that of burning albumen. Upon heating them in a test-tube, and applying litmus paper, the red colour is soon changed to a strongly-marked blue. The ash has a reddish appearance, and consists of peroxide of iron, lime, and phosphoric acid. D. The general chemical relations of the j)lasma [liquor sanguinis) . The plasma of living blood exists as a clear fluid, in which the corpuscles are seen to float. If the blood has been removed for some time from the body, the fibrin separates from the plasma. This separation appears to take place simul- taneously and uniformly throughout the whole of the blood. As the fibrin contracts, it entangles the corpuscles ; the subse- quent contraction tends to expel the serum, and thus the clot is produced. The clot, at first soft and gelatinous, becomes gradually more consistent, and ultimately appears as a mass, capable of a certain degree of resistance, and floating in the scrum. There are certain pathological conditions, under which the BLOOD. 115 blood cannot hold the corpuscles in suspension. There is then formed, previously to the separation of the fibrin, a layer of yellow plasma aboye the sunken blood-corpuscles, in Mhich (i. e. in the plasma), upon the subsequent coagiilation, a cer- tain quantity of fibrin separates (crusta inflammatoria) . In some obseryations on the blood of a cachectic horse, made during the summer, I found that the corpuscles sunk so rapidly in the tumbler in which the fluid was received, that a layer of plasma was formed, amounting to nearly two thii'ds of the whole volume of the blood, previously to the coagulation of the fibrin. The fibrin, which was present in large quantity, then began to coagulate, and after some time a solid cylinder of coagulated plasma was formed, which resisted a consider- able degree of pressure, and under which the uncoagulated blood-corpuscles were distributed. In some pathological states the blood contains mere traces of fibrin ; in these cases no clot is formed ; we observe merely the separation of a few dark gelatiniform flocculi. The coagulation of the plasma is a consequence of the cessation of the vitality of the blood; hence it occurs not merely in blood abstracted from the living body, but after death, and under some peculiar circumstances, in the vessels themselves. It is independent of external influences, for it occurs equally in ordinaiy aii', in vacuo, and in various gaseous atmospheres. It may be accelerated or impeded by certain agents, and may even be altogether prevented; the blood, however, when prevented from coagulating in this manner, is in a state very diff'erent from that in which it previously existed in the body, the fibrin ha\ang undergone a chemical change. The retardation or j)revention of coagulation} Fresh blood becomes solid below 32°, without the coagula- tion of the fibrin, which however occurs after thaAving. ' [A full account of the various experiments by Johu Hunter, Jizxy, Prater, Scuda- more, and others, on the effects of various agents upon the coagulation of the blood, to the period it was written, may be found in Ancell's seventh lecture " on the Phy- siology and Pathologj' of the Blood." Lancet, 1840.] 1 1 6 CIRCULATING FLUIDS : The blood of frozen and apparently dead frogs remains fluids and tlie same is the case in hyhernating animals, in which the temperature of the blood is reduced to that of cold-blooded animals.' The coagulation of the blood is retarded by contact with animal membranes ; it will remain fluid in tied arteries for tlie space of three hours. Blood which has been infused into the cellular tissue "«dll remain fluid for weeks. Schultz has ob- served that blood which has collected in the intestines remains fluid for a long time ; moreover, the blood Avhich has been abstracted by leeches does not coagulate, as long as it remains in the body of the animal. ^ Gerhard, Hufeland, and Kielmeyer have shown that blood through which an electric current is continuous^ passed re- mains fluid for a long time. Schubeler also showed that positive electricity hinders the coagulation of the blood ; more- over, the blood of animals killed by electricity or lightning does not coagulate. The following salts hinder the coagulation of the fibrin, according to Hewson,^ Schultz,"* and Hamburger's'' observa- tions : sulphate of soda, chloride of sodium, nitrate of potash, chloride of potassium, acetate of potash, and borax, if they be added in the proportion of half an ounce to six ounces of blood. If however the blood be diluted with double the quan- tity of water, the fibrin coagulates. (Hewson.) The carbo- nates and acetates prevent the coagulation of the blood, in all degrees of concentration. With regard to the action of the sulphates, a concentrated solution appears to retard the coagulation ; a dilute solution, on the contrary, to accelerate it. (Hamburger.) The same appears to be the case with respect to the tartrates and borates. The following metallic salts impede the coagulation of the fibrin : sulphate of copper, ammoniaco-sulphate of copper, sul- phate of the protoxide of iron, chloride of iron, feiTocyanide ' Schultz, op. cit. p. 80. " L. c, pp. 64 and 81. •* Disquisitio experhnentalis de sanguinis njitura. L. B. 1785. " Op. cit. ^ Experimentorum circa sanguinis coagulationem specimen prinumi diss, inaug. auct. Hamburger. Berolini, 1839. BLOOD. 117 of potassium, acetate of lead, and tartrate of antimony and potash.' Magendie's2 observations differ considerably from the above. He arranges in a tabular form^ the following salts which tend to impede the coagulation of the blood : the alkaline car- bonates, nitrate of potash, and nitrate of lime. All observers agree that the free alkalies completely prevent the coagulation. The observations of Schultz, Magendie, and Hamburger show that dilute mineral and vegetable acids prevent the coagulation of the blood, which however thickens, and assumes a syrupy or oily appearance. These statements have been confirmed by myself. The following non-mineral reagents have been observed by Magendie to prevent or impede the coagulation of the fibrin : nitrate of strychnine, nitrate of moi'phine, and nicotine. This statement, as far as regards the nitrate of strychnine, has been denied by Hamburger. 3 Hunter observed that the coagulation was retarded by the addition of a solution of opium, a statement however which is not confirmed by Hambui'ger. The latter observer notices the effect which is produced by the addition of bile, in pre- venting the coagulation. Acceleration of the coagulation. The coagulation of the fibrin is accelerated, or at any rate not impeded, by a temperature higher than that of the living blood. According to Hewson, it takes place most rapidly at from 114° to 120°. Scudamore and Schroder van der Kolk assert that the coagulation is accelerated by electricity and galvanic currents, which however is opposed to the previous observations of Kielmeyer and others. Contact with atmo- spheric air hastens the coagulation. According to Hamburger, no influence, either in accele- ' Schultz remarked that hydi'ochlorate of ammonia, sulphate of potash, and sul- phate of magnesia, retain the blood in a state of fluidity, and that even the ad(Ution of a large quantity of water does not produce coagulation. After the addition of sulphate of soda, the blood could only be prevented from gelatinising by constant stirring, a step that was not requisite with the other salts. ^ Lefons sur le Sang. BriLxelles, 1839. ' Op. cit. p. 249. 3 lb. p. 4.'). 118 CIRCULATING FLUIDS: rating or impeding tlie coagulation, is exerted by sulphate of lime, clilorate of potash, or iodide of iron.^ According to Magendie and Hamburger, the coagulation is accelerated by acetate of morphine. The former observer states that water, a Avatery solution of sugar, the fluid of dropsy, Seidlitz and Vichy waters, alcohol, ether, and mannite ; and the latter, that decoctions of digitalis, and tobacco, solution of tannin, iodine, solution of sugar, gum arable, starch, and fresh urine, have a similar effect.- ON THE CHEMICAL PHYSIOLOGY OF THE BLOOD. On the formation of the blood. The formation of the blood, and especially of the blood- corpuscles, has been made a subject of careful and laborious research by many of the best microscopic observers of the present age, amongst whom we may enumerate the names of Schultz, Baumgartner, Valentin, Reichert, Wagner, and Schwann. [As the physiological details connected with this subject belong strictly to the physiology rather than to the chemistry of the blood, we shall content ourselves with a brief statement of all that is known with any degree of certainty regarding this obscure and intricate process. Capillary vessels are developed by the stellated union of a certain set of blastodermic or germinal cells ; and no sooner are capillary or other vessels formed, than a kind of blood is found in them. The corpuscles of that blood differ from those of the adult in being considerably larger, more spherical and granular, and in containing a distinct nucleus. There is pro- babl}^ an external envelope. The granules unite or amalga- mate, so as to form the coloured or clear part of the blood- corpuscle, Avhile the nucleus remains. See fig. 2.] Although much light has recently been thrown on the formation of the blood-corpuscle in the embryo, we are still ' Magendie oljserved that the coaguhation is hastened by the addition of the chlo- rides of potassium, sodium, ammonium, and barium ; of bicarbonate of soda, sulphate of magnesia, l)orax, nitrate of silver, iodide of potassium, and the cyanides of gold and mercury. - [A snmmary of Mr. Blake's experiments on the effects of vai'ious salts, &c. on the blood, is given in Williams's Principles of Medicine, page 99.] BLOOD. 119 unfortunately almost entirely deficient in positive information regarding the formation of the blood-corpuscles in the mature indindual. That blood-corpuscles are formed in adults, cannot admit of a doubt ; for we see that the mass of the blood, and consequently of the blood-coi^puscles, is continually increasing from the moment that blood is fii'st produced in the embrv^o, up to the period of full corporeal development. jNIoreover, in- dependently of any considerations founded on the increased mass of the blood, a continuous formation of blood-corpuscles is obviously necessary to compensate for the waste and consumption of blood dependent on the exercise of the A-ital functions. The immense quantities of extractive matters (abounding in nitrogen and carbon), — of urea, lu'ic acid, bile, mucus, and fat, which are daily secreted in the urine, faeces, and mucous discharges, together with the considerable amount of carbon which is given off as carbonic acid in the process of respiration, — must all be refunded to the system by the blood. To this it may be objected, that the supply takes place on the part of the plasma, which alone therefore would requii'e to exist in a state of continuous in- crease, while the corpuscles coexist, and are coeval with the individual in whose blood they occui'. Such a view is, how- ever, at variance with all the phenomena of the higher stages of existence ; for no tissue or portion of the body, solid or fluid, is allowed to remain unchanged or unendowed with vi- tality. The necessity for the consumption and reproduction of the blood-corpuscles has never yet been disputed, but various theories have been propoianded by different physiologists re- garding the seat of their formation and their mode of organic development or metamorphosis. Hewson endeavom's to show that the spleen is the principal organ in which the blood-corpuscles are formed, and that they are produced from lymph- granules. Although the functions of the spleen are not even at the present day properly deter- mined, it is an established fact that the spleen ma}- be extir- pated, and the formation of blood not be impeded ; moreover, the red colour of the lymph, upon which Hewson strengthens his opinion, has not always been observed.^ Schultz" con- '^J.'Miiller's Handbuch der Physiologic, vol. 1, p. 573. * System der Cirkulation, p. 37. 120 CIRCULATING FLUIDS : siders tliat the blood-corpuscles are formed in the lymphatic glands, and conveyed by the ductus thoracicus into the blood. He states that the chyle which is found in the vessels issuing from the glands, contains clear, round, oily vesicles, and granular lymph-corpuscles. The diameter of the granular lymph- corpuscles in horses and rabbits varies from "0005 to •0008 of a line ; and they are so similar to the nuclei of the blood- corpuscles, as to render it very probable that the latter are de- rived from them. In the lymph of the ductus thoracicus of rabbits and horses, we find actual blood-corpuscles, as well as the transparent and granular lymph-corpuscles ; these blood- corpuscles, however, possess more tender, and not perfectly flattened capsules, and a much smaller amount of colouring matter than when they have arrived at maturity. They are consequently paler and more transparent than at a subsequent period, and the nucleus may be inclosed more or less closely in the capsule. The lymph-corpuscles and the nuclei of the blood-corpuscles present a very close analogy, for they both vary in size, and, to use Schultz's own words, " it cannot be doubted that the blood-corpuscles are produced by the forma- tion of a colom*ed capsule around the lymph-globules."^ These blood-corpuscles could not have been transmitted there by blood-vessels ; their difference from the mature cor- puscle, and their slight amount of colouring matter, are opposed to such a supposition. Since lymph-corpuscles also pass into the blood, the formation of blood-corpuscles from them in the blood-vessels cannot be denied ; it may however happen that they are again conducted by the blood to the lymphatic glands, where their metamorphosis is completed. In a more recent Avork on the Blood,^ Schultz states that the coloured capsule of the blood-corpuscle is principally formed in the process of re- spiration. There is much in favour of this view, for we know that the blood can only obtain its nutriment through the ductus thoracicus, and it seems obvious that the conditions necessary for the formation of the blood- corpuscles must he as- sociated with the circumstance of the derivation of the nutriment from this source. Moreover, there can be no doubt that in conse- ' L. c, p. 45. * Ueber die geliemmte Aiiflosung und Ausscheidung der verbrauchten Blutblaschen. Ilufeland's Journal, April 1838. BLOOD. 121 quence of the continuous supply of cliyle which is afforded to the blood, the lymph-corpuscles would speedily predominate, unless they underwent some metamorphosis, and assumed another form ; but in reality the number of lymph-corpuscles in the blood is comparatively small. Although the Ijmphatic glands may be regarded as in some degree the seat of formation of the blood- corpuscles, it must by no means be supposed that the latter issue from these glands in a perfectly developed state ; their ultimate maturity is obtained in the blood, and they aid in the support of its independent vitality. Henle, who likewise coincides in the view just given, as I know from a personal communication with him, has minutely studied the formation of the blood- corpuscle from the honph-corpuscle, and the transitions of the latter to a state of maturity. He regards the lymphatic glands as the chief, although not the exclusive seat of formation of the blood-corpuscles. Although the chyle does not contain a sufficient number of matured blood-cor- puscles to allow us to recognize their presence by its external appearance, we must remember that dimng its continuous dis- charge into the subclavian vein, a considerable number of blood-corpuscles may in a certain time be conveyed into the blood : that the blood-corpuscles which are contained in the chyle are formed in the organs of chylification, and are not conveyed thither by arteries or veins, is clear from our knowledge of the connexions between the vascular and capillary systems. It is pretty generally allowed that the process of respiration is essentially requisite for the further development of the young blood-corpuscles, after their formation in the lymphatic glands. J. Miiller, in his chapter on the formation of the blood, expresses himself to the effect that the contents of the lymphatics, namely the clear lymph and the whitish chyle, are the materials for the formation of the blood, and that this formation is carried on not in any one particular organ, but under the combined influence of the vital functions generally. This view corresponds with the former, if in the materials for the formation of the blood we understand the young blood- corpuscles, (i. e. the lymph- and chyle-corpuscles which are to be changed into blood-corpuscles,) and the plasma, which is still almost destitute of fibrin. If, however, the lymph- and chyle-corpuscles are regarded as having no connexion with the 122 CIRCULATING FLUIDS : genesis of tlie blood-corpuscles, then it is distinct from the previous views. Reichert in liis work on Development, lias said nothing respecting the formation of blood-corpuscles in the adult ; but from a personal communication, I find that he regards the liver as the blood-preparing organ in adults, and the preparation of the blood as the principal function of that gland ; the secretion of bile must then be regarded as a conse- quence of the metamorphosis that occurs during the above process. On the forces that circulate the blood. The due performance of the functions of circulation and respiration is as essential to the metamorphosis of the blood as it is to life itself. Circulation commences in the foetus with the rhythmic movements of the heart. Reichert ' has observed in the incubated e^^, that the only in- dependently formed canals for the blood are the great vascular trunks directly connected with the heart; the other blood-vessels are, as it were, excavated by the force of the heart's action on the blood-cells in the loose celkdar mass of the early embrj^o. The action of the heart is the primum movens of the cir- culation. Burdach^ observes that the ^dtal action of the heart, which acts mechanically on the blood, and propels it in certain directions and courses, indicates most clearly that the heart comprehends within itself the elements of the circulating power, and that independently of its vital activity, the whole circle of phenomena appertaining to it results from its mere mechanical relations. The cause of the heart's action must be referred to the irritation produced in it hj the living blood. Miiller ^ also considers that the blood is chiefly propelled by the rhythmic action of the heart. The view taken by Schultz ^ is difi'erent : he considers that the motion of the blood in the living body results from the joint influence of the blood and of the vessels reciprocally acting on each other, whose true nature can only be seen in the vital relations, audits aim in the circle of organic functions. R. Wagner^ is inclined to believe that the blood is propelled » Op. cit. p. 142. 2 Op. cit. vol. 4, p. 163. 3 Op. cit. vol. 1, p. 163. " Op. cit. p. 244. * Zur vergleichenden Physiologic des Blutes, 1833, p. 70. i BLOOD. 123 not merely by the heart's action, but also by a certain electric attraction of the organs, by the influence of the nerves, and by a motive power inherent in the blood itself. Since the heart's action is occasioned by the irritation exercised upon that organ by the living blood, there can be no doubt that the reciprocating action of the organs and of the blood must influence the circulation. Schultz evidently undervalues the influence of the rhythmic motion on the circulation, when he limits the functions of the heart to the conveyance of arterial blood to the peripheral system, and to the conduction of venous blood back again, and regards the blood in the peri- pheral system as moving entirely independent of it. The cnculation is usually divided into the greater and the lesser. There is however, in fact, but one circulation; and this is divided into the greater course, which proceeds from the left heart through the arteries of the body, and through the veins to the right heart, and into the lesser course, which recon- ducts the blood through the lungs from the right to the left heart. On the pi'ocess of respiration. Kespiration takes place through lungs, gills, tracheae, or the integument. Oxygen is indispensable for the process, although pure oxygen is less conducive to health than a mixture of oxygen with a gas not detrimental to life, as nitrogen or hydrogen. The proportions of oxygen and nitrogen that occur in atmo- spheric air are doubtless the most suitable for the respiration of the higher animals ; viz. 21 parts of the former, and 79 of the latter gas. In an atmosphere of pure hydrogen or nitro- gen, a man would run the risk of sufi'ocation in a very few seconds, not because these gases are themselves poisonous, but simply from the absence of oxygen. Many gases produce a directly poisonous efi'ect, and cannot be breathed even when mixed with oxygen ; as, for instance, arseniuretted hydrogen, sulphuretted hydrogen, phosphoretted hydrogen, carburetted hydrogen, carbonic oxide, cyanogen, chlorine, ammonia, and many others. As a consequence of the process of respiration, the blood becomes chemically changed; this change is almost entirely confined to the blood-corpuscles, which in this independent 124 CIRCULATING FLUIDS : act of metamorphosis represent exactly what we understand by the vitality of the blood. Respiration in man and the mammalia is effected by the dilatation and contraction of the cavity of the thorax. Since the diaphragm in a state of relaxation is arched, and in a state of contraction during inspiration becomes flattened, the cavity of the thorax is increased during inspiration, the surface of the lung follows the retreating walls, its volume becomes enlarged, and the atmospheric air rushes into its cells. The branches of the air-tubes ramify to an extraor- dinary degree in the parenchjTua, and their most minute ex- tremities terminate in vesicular dilatations, which do not com- municate with each other, and whose walls are covered with the peripheral capillary network. From a calculation of Lie- berkuhn,' it would appear that the whole surface of the ramify- ing air-tubes in man amounts to 1400 square feet, on which extraordinary surface the blood and atmospheric air are in contact with each other, (being separated merely by a moist, permeable membrane,) and the former absorbs the required amount of oxygen. Davy calculates that the human lung after the strongest expiration, still contains 35 cubic inches of air ; after an ordinary expiration 108 cubic inches ; after an ordinary inspi- ration 118, and after a very deep inspiration 340 cubic inches. In ordinary inspiration and expiration (about 26 or 37 in the minute) the amount of air that is changed varies from 10 to 13 cubic inches. According to Herbst, full-sized adults usually inspire from 20 to 25 cubic inches; persons of smaller stature from 15 to 20. The volume of air inspired during each respiratory act is fixed by Allen and Pepys at 16-5, by Abilgaard at from 3 to 6, and by Thomson at 40 cubic inches. The quantity of air that enters the lungs in the course of 24 hours is calculated by Davy at from 400,000 to 500,000 cubic inches, by Allen and Pepys at from 460,800 to 475,200, and by Thomson at as much as 1,152,000, or 52*5 pounds, the respirations in this case being 20 in the minute. ^ Atmospheric air once respired is lessened in volume ; and • Scliultz, op. cit. p. 288. ^ Ginelin's Handlnich ricr tlieoretisclien Chciuie, vol. 2, p. 1519. BLOOD. 125 the loss has been variously estimated by Berthollet, PfafF, and Davy at from 1-2 7th to l-lOOth of its bulk. Allen and Pepys, however, found the loss not more than l-16Gth, or about O'G^, and they looked upon the former as a mere error of obser- vation. The most important experiments regarding the changes which atmospheric air undergoes in respiration, are those of Allen and Pepys/ of Dulong,^ and of Despretz.^ The earlier experiments of Allen and Pepys showed that the quantity of oxygen lost was exactly replaced by the car- bonic acid generated, and that nitrogen was given oiF. In their later experiments, it appeared that more oxygen was absorbed than the quantitj^ of carbonic acid expired ac- counted for ; they were also further conAdnced of the accuracy of their former observations respecting the increased quantity of nitrogen which is expired. They caused animals to breathe an atmosphere of pure oxygen, and likewise of oxygen mixed with three times its volume of hydrogen. In the latter case a portion of the hydrogen disappeared, and was replaced by an equal volume of nitrogen. The experiments of Dulong were conducted with great ac- cui'acy, and by means of apparatus expressly prepared for the purpose. They showed that more oxygen is consumed than is replaced by the carbonic acid formed. The quantity of oxygen thus lost, and not replaced by carbonic acid, amounted in the case of herbivorous animals to about 10^ of the oxygen wliich was changed into carbonic acid; in carnivorous animals the minimum excess amounted to 20, and the maximum to 50^. The observations of Despretz confirm the residts obtained by Dulong, and likewise shoAV that nitrogen is developed during respnation. The following table presents a sketch of the residts of the observations made by Despretz ; the calculations are founded on the French litre : — > Schweiger's Journal, vol. 1, p. 182; aud vol. 57, p. 337. Pliil. Trans. 1809, p. 410. 2 lb. vol. 38, p. 505. 'Aunales de Chimie et de Physique, vol. 26, p. 337. 126 CIRCULATING FLUIDS Air before the Ex- periment. Air after the Experiment. Excess of Oxygen over Car- bonic Acid formed. Nitrogen Nitrogen. Oxygen. Nitrogen. Oxygen. Carbonic Acid. developed. Rabbits . . 37-914 10-079 38-743 6-023 3-076 0-980 0-839 Leverets 39-085 10-389 39-517 6-216 2-955 1-218 0-432 Guinea-pigs 37-957 10-089 39-023 6-790 2-588 0-707 1-066 Dog . . 37-649 10-008 39-022 4-424 3-768 1-806 1-374 Puppies . . 37-176 9-882 38-273 3-649 4-018 2-215 1-097 Tom Cat . 37-830 10-055 38-354 7-125 2-060 0-870 0-524 Pigeons . . 37-662 10-012 38-372 6-826 2-451 0-735 0-710 Great Owl . 38-027 10109 38-754 7-483 1-601 1-025 0-727 The quantity of carbonic acid formed in tlie process of re- spiration in twenty- four hours in adults, and the amount of carbon contained therein, have been calculated as follows : Lavoisier and Seguin Menzies Dav7 . Allen and Pepj's . Expired Carbonic Acid Carbon Cubic in. 14930 31680 39600 Grains. 8584 17811 18612 Grains. 2820 4853 5148 Consumed Oxygen. Cubic in. 46037 51480 45504 39600 Grains. 15661 French. 17625 English. 15751 „ 13464 „ The large amount of carbon, from 11 to 13 ounces, (Davy, Allen, and Pepys,) that is thus carried off by the lungs in the twenty-four hours, does not accord with the other phenomena of nutrition ; and Berzelius has calculated that it would require 6i pounds of solid food daily to make up for the carbon that is separated by the lungs alone, without taking into consider- ation the very considerable amount that is also removed by the urinary secretion. And further : when we consider that in most sorts of food the portion which is converted into chyle is much less than that which is carried off by the intestinal canal in the form of faeces, it becomes the more wonderful how so many persons can exist on a few pounds of daily food, the solid constituents of which must be very small, and of which only a still smaller part admits of assimilation ; and we cannot help agreeing with Berzelius, that so large an excretion of carbon is inconceivable, and that in all probability there is some fallacy in the experiments, Prout has made some interesting observations respecting the development of carbonic acid from the lungs at different BLOOD. 127 periods of the day. He found that during equal spaces of time the minimum occuiTed duiing the middle of the night ; towards morning it increased, and attained its maximum be- tween 11 and 1 o^ clock ; it then gradually diminished till about 9 p. m.., when it remained fixed at its minimum till 3 a. m. The quantity of carbonic acid was likewise found to increase by gentle exercise, especially at its commencement, and when the barometer was low. The mean amount of carbonic acid per cent, was 3-45. [A series of similar experiments has been published by Mr. Coathupe, which differ in several respects in their results from those of Prout. They were continued for a week. The fol- lowing is the result obtained : Carbonic acid per cent, of air expired. From 8 a.m. to 9^ . . . . 4-37 10 a.m. to 12 . . . . 3-90 12 noon to 1 .... 3-92 2 p.m. to 51 . . . . 4-17 7 p.m. to 8i . . . . 3-63 9 i).m. to midnight . . . 4-12 — Mean 4-02. Macgregor ascertained that the air expired by persons ill of confluent smallpox contained as much as 8^ of carbonic acid. During the eruptive fever of measles, it amounted to from 4 to 52 j and in proportion as the health was restored, the per cent- age was diminished to its natural standard. In chronic skin diseases an augmentation was likewise observed ; and, in a case of ichthyosis, the mean per centage was 7 2 ; in tjqihus, ac- cording to Dr. Malcolm,' the formation of carbonic acid is di- minished; in diabetes, no deviation from the normal standard could be detected. The question of the quantity of carbonic acid expired by a person in twenty-four hours has lately become of pecuhar inte- rest, in consequence of its association with several problems of high physiological importance. Liebig has endeavoured indi- rectly to estimate the quantity by comparing the amount of carbon contained in the food consumed in the twenty-four hours, with the carbon of the excretions during the same period, and estimating the diflFerence as the quantity separated by the respu-atory process. He thus found that an adult, taking moderate exercise, expires daily on an average 13-9 ounces of carbon (more than double the quantity found by Lavoisier.) ' London and Edinburgh Monthly Journal of Medical Science, 1843, page 1. 128 CIRCULATING FLUIDS : Experiments have recently been made by Andral and Gavarret^ Scbarling, and Brunner and Valentin, with the xieyv of ascertaining this point, and of elucidating the chemical bearings of this department of physiology. We shall endeavour to give, as briefly as possible, their most important results. Absolute quantity of expired carbonic acid. Andral and Gavarret expressed their results per hour, are contained in the following table : They MALI SEX Carbon Carbon exhaled exhaled Age Muscular development. per hour. Age. Muscular development. per hour. 8 Moderate prrains 67-0 37 Moderate grains 164-7 10 Very great 104-7 40 Very great 186-3 12 Moderate 113-9 45 Very slight (mean of 4) 132-4 12 Great 127-8 48 Good 161-7 14 Moderate 126-2 50 Good 164-7 16i Good 157-0 54 Very great 163-2 18 Good 169-4 59 Moderate 154-0 20 Good 166-3 60 Extraordina rily great 209-4 24 Moderate (mean of 2) 176-6 63 Extraordinarily great 190-9 26 Extraordinarily great \ 2171 217-1 64 68 Slight . Moderate 133-9 147-8 26 Moderate 169-4 76 Slight 92-4 28 Good 190-9 92 Extraordinarily great 135-5 32 Good 176-6 102 Extremely diminished 90-8 33 Moderate (mean of 6) 164-7 FEMAL E SEX. Periods Muscular Carbon Periods Muscular Carbon of develop- exhaled of develop- exhaled life. Age. ment. per hour. life. Age. ment. per hour Prio r to the ^10 Good . 92-4 r-38 Moderate 120-3 appearance J 11 Good . 95-4 42 Good . 127-8 of the ] 13 Great . 970 44 Very great 152-4 catamenia. 1-15 J Very great 109-3 After 49 Moderate 113-9 -15| Moderate 97-0 cessation 52 Moderate 115-5 19 Very great 107-8 Of 56 Moderate 109-3 During 22 Good . 103-1 catamenia. 63 Moderate 106-2 mensti-ual - 26 Slight . 92-4 66 Moderate 104-7 life. 26 Moderate 97-0 76 Very great 101-4 32 Moderate 95-4 82 Moderate 92-4 -45 Moderate 95-4 3 months pregnant. . i« Good . 120-3 5 mo. do. 32 Good . 126-7 7^ mo. do. 18 Slight . 112-4 8i mo. do. 22 Good . 129-3 BLOOD. 129 It is thus seeu that, in general, the amount of carbonic acid expired by both sexes increases with age up to a certain point — the 40-45th year, and then diminishes ; tliat the quantity of carbonic acid expired increases with the development of the muscular system ; that women expire less carbonic acid than men; that the formation of carbonic acid attains its max- imum at the commencement of menstruation, and then expe- riences no further increase, except in the pregnant state, until the cessation of menstruation, when an increase again takes place. On an average, an adult male, of moderate constitution, exhales from 160 to 170 grains of carbon per hour; an adult female in the unimpregnated state, from 100 to 110 grains; during pregnancy, 125 grains ; and after the cessation of the catamenia, from 116 to 130 grains. Dumas also found 154 grains per hour as the average quantity of carbon exhaled by an adult male. Scharling's experiments were made on the following indi- viduals : 1st, a male, set. thirty-five, weighing 131 lbs. ; 2d, a male, set. sixteen, weighing 115ilbs. ; 3d, a soldier, tet. twenty-eight, weighing 164 lbs. ; 4th, a girl, set. nineteen, weighing 11 li lbs. ; 5th, a boy, set. nine and three-quarters, weighing 44 lbs. ; and 6th, a girl, set. ten, weighing 46 lbs. The carbon exhaled per hoiu' amounted to — No. of Amount No. of Amount the of carbon Remarks. the of carbon Remarks. person. grains. person. grains. 1. 145 Fasting 3. 137-8 Asleep In June r After breakfast and a \ walk In 111-9 Fasting when 190 October. 159-4 1 Fasting, after break- very 130 Hungry fast and work hot. 165 2 hoiu-s after dinner 188-9 After dinner 160 After tea 194-7 3 hours after dinner 100 Whilst asleep 178-3 After work 114 4. 122-3 Whilst asleep Sleepy 2. 98-9 Whilst eating In June 144-2 Fasting In 91-3 Fasting when 139-8 Fasting and hungry October. 92-6 After supper very 177 r ^ an hour after break- 133-8 1 hour after breakfast hot. 1 fast 1170 1 hour after dinner 167-7 J 2. J hours after break- L fast 108-9 Whilst eating 180-8 2 hours after dinner 130 CIRCULATING FLUIDS: No. of Amount No. of Amount the of c.irbon Remarks. the of carbon Remarks. person. grains. person. grains. 5. 7G-2 Fasting 6. 65-5 Whilst asleep In 94-8 \Miilst at breakfast In 95-3 After breakfast Autumn. 113-8 After breakfast Autumn. 103-0 After dinner 119-3 1 hour after dinner 99-0 Shortly after tea 84-5 2 hours after supper 751 WhUst asleep 74-8 Whilst sleepy Supposing that adults sleep seven and children nine hours per day, the amount of carbon consumed is on an average — In twenty-four hours. In one hour. 1. 3380 grains. 141 grains. 2. 3455 144 3. 3692 154 4. 2555 106 5. 2050 86 6. 1932 80 It is thus evident that the quantity of carbonic acid ex- pired is very variable, and that it may be altered by many cii'cumstances. Hunger and rest diminish, satiety and labour increase it. It is greater during the day than the night, in the proportion of 1'237 to one. If the expired carbonic acid be estimated in relation to the weight of the body, it is found that childi'en give ofl" a proportionally greater amount of this gas than adults. In some forms of disease, the amount of expired carbonic acid falls below the standard ; it seems, in a state of health, to vary directly with the acti\dty of the circu- lation. The influence of muscular activity on the amount of carbon consumed, has been clearly shown by some experiments made by Dr. Hofmann during a pedestrian tour. His diet was simple and scanty, he took no drink, walked dming the whole day, weighed all his food and every excretion that could be weighed (even the nasal mucus), as well as himself; he then found that the weight lost by the body was never equalled by the excess of the excrements over the food, and that there was a constant loss of matter by the skin and lungs, which amounted to more than 1 lb. We must pass over the details of his experiments. Brunner and Valentin found that the weight of carbon they consumed per hour varied from 134 to 170 grains, and averaged 160. The volume of expired carbonic acid per hour, on an BLOOD, 131 average, was equal to 21-8 litres/ and the entire volume of the air expired per hour on an average equal to 540 litres. These results agree well with those of the earlier observers. When the corrections for moisture are made, the quantity of carbon expired per hour is equal on an average to 172 grains, and of carbonic acid 23-5 litres. B. Relations of the constituents of the expired air to the theory of respiration. On this point Brunner and Valentin only have experimented. They found — Individual. No. of experiments. Volume per cent. '^"^"'"'^ T"" *'^"'' u "'^"°° to the atmosphere. Mean of CO^. O. N. Disappeared O. Difference of N. Brunner f 12 exp. 1st series 4-356 16007 79-547 4720 + 0-362 1 4 exp. 2d „ 3-825 16306 79-869 4-508 + 0-683 Thomas . 4 exp. 1st „ 4-673 15-895 79-432 4-920 + 0-329 Valentin / ^ ^^P' ^^* " ^'^^^ \&-\^^ 79-541 4-671 + 0-356 1 12 exp. 2d „ 4-641 15-783 79-576 5-032 + 0-391 Total average 4-380 16-033 79587 4-783 + 0-402 Weight per cent. Brunner / 12 exp. 1st series 6-522 17-428 76-050 5-582 — 0-940 1 4 exp. 2d „ 5-749 17-735 76516 5-275 — 0-474 Thomas . 4 exp. 1st „ 6-975 17-165 75-860 5-845 — 1-130 Valentin I ^ ^^P' ^** " ^'^^^ ^^"^^^ ''^'^^'^ ^'^-^ — ^'^29 1 12 exp. 2d „ 6-945 17-089 75-965 5-920 — 1-025 Total average 6-546 17373 76081 5-637 — 0-909 It is thus evident that the variations observed in the amount of nitrogen are entirely within the errors of observa- tion, and the nitrogen may be disregarded in the process. Again, the expired air contains a volume of carbonic acid, which is but little less than the volume of oxygen which has disappeared (therefore the weight per cent, of the carbonic acid is necessarily somewhat greater than that of the absorbed oxygen, and thus also the difference of nitrogen appears positive as regards volume, but negative as regards weight) ; so that all the oxygen absorbed reappears as carbonic acid, except a small quantity consumed in the body for other pm'poses. Noav, according to Graham^s law of the diffusion of gases, when they are separated by an animal membrane and are under equal pressure, they become mixed inversely as the square roots of [' The litre is a little larger than the English wine quart ; the litre being equal to ■•1-028, and the quart to 57-75 cubic inches.] 132 CIRCULATING FLUIDS : their densities 5 consequently, 1-17585 volume of oxygen is absorbed for one volume of expired carbonic acid. Comparison of the figures shows us that the mixture of the two gases in respiration takes place entirely according to the law of diffusion of gases ; for the most accurate method of experimenting gave results, in which the figures obtained for the carbonic acid and absorbed oxygen, almost exactly agreed with those reckoned according to the law of the diffusion of gases : Volume per cent, of the expired air. CO.,. 0. N. 3-850 16-270 79-185 Oxygen absorbed. 4-690 Carbonic ac calculated. 3-994 d + Difference. 0-144 per cent 3-593 16034 79-185 4-931 4-199 + 0-606 „ 3-949 16-090 79-185 4-887 4-162 + 0-213 „ 3-777 16-090 79-185 4-914 4-192 -f 0-415 „ 3-759 16095 79-185 4-922 4-192 + 0-433 „ 4-483 15-328 79-185 5698 4-853 + 0-370 „ 4-752 14-733 79-185 6-362 5-418 + 0-660 „ 4-588 14-852 79-185 6-253 5-325 + 0-737 „ In respiration, which is thus a purely mechanical process, the inspired air is first warmed to 99°* 5, and saturated with moisture at this temperature, which is rapidly accomplished on account of its extensive distribution. It then experiences a sim- ple diffusion; the nitrogen remains entirely unaffected; 1"1742 volume of oxygen is absorbed, and replaced by 1 volume of car- bonic acid which is expired ; or for each volume of oxygen ab- sorbed '8516 volume of carbonic acid appears. In consequence of the accuracy with which the law of diffusion is here observed, the most minute portion only of other gases is absorbed or expired. That hydrogen, carburetted hydrogen, and carbonic oxide gases are not contained in the expired air, the authors have shown by some direct experiments ; but small quantities of organic matters are evolved during respiration, as is shown by sulphuric acid, through which expired air has been made to pass, being always coloured red.] i Various opinions have been promulgated respecting the formation of carbonic acid in the blood. The most natural and probable is that of Lagrange and Hassenfratz, who maintain that the blood takes up oxygen in the lungs and retains it in a ' [For further iuformation on this suhject, the reader is referred to Valentin's Lehrhuch der Physiologic, 1844, vol. 1, pp. 507-580, or to an excellent abstract that appeared in the Chemical Gazette.] BLOOD. 133 state of solution. The blood-corpuscles absorb from this con- stant source a due supply of oxygen for their change. The metamorphosis occurs in the peripheral system, and, for the most part, in certain organs, as, for instance, the kidneys. The blood-corpuscles give up the carbonic acid, thus formed, to the blood, aud it is thrown off by the lungs. It must be remembered that blood ahrays contains carbonic acid and oxygen, but arterial contains more of the latter and less of the former than venous blood ; also, that the whole of the carbonic acid is not separated by the lungs, although, when the blood reaches those organs, it is perfectly free from oxygen. Although the atmospheric air and the circvilating fluid are not brought into absolute contact, there is no impediment to their mutual action. The absorption of the air through the humid membrane that suri'ounds the parenchyma of the lungs is facilitated by the immense extent of surface presented, over the whole of which a thin stratum of blood is distributed, and simultaneoTisly exposed to the atmospheric influence. The permeability of the soft tissues, especially of the membranes, by fluid and gaseous substances, is a well known fact. It is in accordance with this law that atmospheric air finds its way into the blood. Dark red blood, inclosed in a moist bladder, soon assumes a bright red tint ; a gas inclosed in a similar receptacle is found, after some time, to be partly dis- placed by atmospheric air. These are mere illustrations of the same principle. If the opinion that has just been given be correct, then carbonic acid and oxygen must be present both in venous and arterial blood. Numerous experiments have been instituted with the view to determine this point. By submitting 12 ounces of the venous blood of a calf to a heat of 200*^, Sir H. Davy obtained I'l cubic inch of carbo- nic acid, and 7 of oxygen, and the experiment has been con- firmed by Brande and Vogel. Stromeyer, Bergemann, ]\Iuller, and others have failed in obtaining carbonic acid from blood in this manner. Brande and Vogel found that blood placed in vacuo developed a gas which contained some carbonic acid, and their statement is confirmed by Home, Bauer, and Reid Clanny, while J. Da\y,i INIitscherlich, Tiedemann, Gmelin, and Midler ' [Dr. Davy has recently shown that gas is frequently, although not invariably, disengaged hoth from venous and arterial blood in vacuo. Researches, Physiol, and Anat. vol. 2, p. 153.] 134 CIRCULATING FLUIDS : failed in observing any development of carbonic acid under the air-pump. Hoffmann and Stevens could not obtain carbonic acid eitlier by the application of heat or by the air-pump ; but they ob- served that if freshly-drawn blood be shaken with hydrogen^ carbonic acid is then evolved. Another experiment in favom* of the existence of carbonic acid in the blood has been insti- tuted by Mliller. Nysten and CoUard de Martigny made animals inhale gases entirely devoid of oxygen^ and observed the formation of carbonic acid. Miiller and Bergemann made frogs breathe pure hydrogen and nitrogen, and observed that, after the animals had remained in these gases from 6 to 22 hours, they had expired a quantity of carbonic acid, varying from 0-25 to 0-83 of a cubic inch. Magnus has published a series of accurate experiments which must be regarded as quite decisive respecting the amount of carbonic acid and oxygen in arterial and venous blood. He passed a current of hydrogen through recently drawn blood, and found that carbonic acid was given off in a constantly de- creasing ratio. He likewise analysed the whole of the gas that he obtained from the blood, and found its composition as follows : Volumes in cubic centimeters. Gas. r 5*4 CO2 Blood of a horse .... 125 . yielded 9-8-^ 1'9 L 2-5 N 8-8 CO2 Venous blood of a horse . . 205 . . . 12-2 ■{ 2-3 O 11 N 10-0 CO, Ditto 195 iiu-u u< 2-5 1-7 N 10-7 CO, Arterial blood of a horse . . 130 . . . 16*3 J 4-10 1 1-5 N r 7-0 CO2 Ditto 122 .. . 10-2 J 2-2 I 1-0 N rl2-4 CO2 Venous blood of the same horse . 170 . . . 18-9 < 2-5 L 4-0 N Arterial blood of the calf . . 123 f 9-4 CO2 14-5 j 3-5 L 1-6 N BLOOD. 135 Volumes In cubic centimeters. Gas. r 7'0 CO.^ Arterial blood of the calf . . 108 . yielded 12-6 j 3-0 O L 2-6 N [-10-2CO2 Veuous blood of the same calf . 153 . . . 13'3-< 1-8 I 1-3 N r 61 COj Ditto 140 . . . 7-7«^ l-OO L 0-6 N From these experiments, it follows, 1st, that carbonic acid, oxygen, and nitrogen exist both in arterial and in venous blood ; and, 2dly, that the quantity of oxygen is greater, and the quan- tity of carbonic acid less in arterial than in venous blood, a fact which confirms the opinion we have expressed regarding the formation of carbonic acid and the theory of respiration generally. The bright coloiu' which is communicated to the blood by oxygen, as well as the dark shade that is induced by the trans- mission of carbonic acid through it, are the actual shades of colour that we see in arterial and venous blood. Moreover, when blood has been rendered artificially venous in this way, it may be rendered arterial in its colour by agitation with a certain quantity of oxygen, and we can then obtain from it a mixture of oxygen and carbonic acid. We have now enumerated the most interesting phenomena in reference to the expired air. We have ah-eady noticed the circumstance that nitrogen is expii-ed. It follows natiu-ally that this gas, which forms the principal constituent of the atmosphere, should be inhaled; and, according to Edwards, there is a sort of compensation between the amount of exhaled and inspired nitrogen, so that the quantity of this gas in the atmosphere remains fixed, the amount of expired nitrogen pre- dominating at one time, and of inspired nitrogen at another. According to Berzelius, the portion of nitrogen taken up by the blood is only changed when the blood comes in contact with a gas which either contains no nitrogen or which possesses it in a greater ratio than atmospheric air. Nitrogen is there- fore evolved from the blood during the inspiration of oxygen or hydrogen, and the circulating fluid is then found to contain a greater proportion than usual of oxygen or hydi'ogen ; but if nitrogen is inhaled, an excess of this gas is found in the blood, while oxygen and carbonic acid are evolved in accordance with the known law of the diffusion of gases. 136 CIRCULATING FLUIDS : In tlie air after expiration we always find a greater or less amount of wateiy vapour. According to Menzies, an adult man^ in the course of twenty -four hours, gets rid, in this man- ner, of 2880 grains of water. Abernethy fixes the amount at 4320; Thomson at 9120; Hales at 9792; and Lavoisier at as much as 13,704 grains. This water exhales from the blood which is circulating in the bronchi and cavity of the throat, and contains some animal matter which causes it to decompose speedily. Alcohol, ether, and substances of that nature are removed from the blood by the lungs, at least in part ; for after they have been taken, their odour may be distinctly recognized in the breath. Sulphuretted and phosphoretted hydrogen, if injected into a vein, are easily recognized in the breath by the odour ; and if phosphoretted oil is applied in a similar manner, dense white vapours of phosphorous acid are speedily exhaled. Respiration of the fcetus and of animals. As the function of respiration in the embryo of the mam- malia cannot be carried on by the lungs, an equivalent is supplied to them by the influence of the maternal fluids on those of the foetus, in the placenta. Anatomical investigations have shown, that it is impossible for the blood of the mother to be transmitted unchanged into the foetus ; nutriment and arterial blood can only make their way into the foetal system through the medium of cells. In the umbilical cord there are two vessels which convey venous blood from the foetus to the placenta, and there is one that conducts arterial blood from the placenta to the foetus. The changes which are efi"ccted in this manner in the foetal blood are not so obvious as if they had occurred in the ordinary manner in the lungs ; in fact it is by no means easy, or in- deed ahvays practicable, to detect wcvj diff'erence in the colour of the arterial and venous foetal blood. The change, however, such as it is, is of the highest importance to the foetus, since it dies if the umbilical cord be tied before birth. The anato- mical peculiarities in the circulating system of the foetus are too well known to require any description. In the embryo of birds the respiration is carried on during the later stages of development, by the allantois, an extremely vascular membrane, over which the left umbilical arterv is BLOOD. 137 especially distributed. The embryo is ultimately entirely in- closed in the allantoide (the chorion of V. Baer,) and is inti- mately connected with the membrane of the shell. The mutual action of the allantoide and the atmosphere, takes place directly through the membrane of the shell, and the shell itself, and thus it may be regarded as a proper respiratory organ, whose development has corresponded throughout with that of the embryo. In birds, the lungs do not occupy the whole of the thoracic cavity, but are placed in its furthest extremity: the thoracic and abdominal cavities are not separated by a diaphragm. Openings are situated on the surface of the lungs which admit the air from those organs into the large cells situated around the pericardium and between the viscera of the abdomen: the air can pass from these cells even into the cavities of the bones. Respiration is conducted in fishes much on the same prin- ciple that it is in the foetus of the mammalia. The venous blood is conveyed to the gills, where it circulates in the capil- laries, and absorbs oxygen and nitrogen from the air which is contained in the water, and in this way it becomes arterialized. Humboldt and Proven9al have carefully studied the process of respiration in fishes, and have proved that they take up oxygen and nitrogen from the air Avhich is diftused through the water, and that they exhale carbonic acid ; that the qiiantity of oxygen which they absorb is more than is replaced by the carbonic acid expii-ed; that fishes absorb oxygen from boiled water which has been subsequently impregnated with half its volume, but that they only survive in it for a short time; and, lastly, that they die in water from which the air has been removed, or in which they have respired for any time. The water (from the Seine) in which these experiments were conducted contained from -0266 to -0287 of its volume of atmos- pheric air, of which from '306 to '314 was oxygen. The amount of carbonic acid varied from "06 to '11 of the volume of atmos- pheric air. The water was inclosed in bell-glasses over mercury, through which the fishes were introduced into it. In experiments with tenches they observed, that from 100 parts of atmospheric air there were abstracted 22-8, 13-6, 23-4, 15-5, 17-4, 22-8 parts, the variations depending on the duration of the experiment 138 CIRCULATING FLUIDS : and the number of the fishes. The ratios of the consumed oxygen to the carbonic acid formed, were as 1 to '57, "80, '91, •20, and '50, while the ratios of the consumed oxygen to the consumed nitrogen were as 1 to '43, -87, "40, -19, '71, and -63. The inequahty of these ratios indicates, as Berzelius remarks, the yarying power with which fishes act upon the air on dif- ferent days, at different seasons, and possibly in different con- ditions of health.^ The amount of oxygen consumed by fishes is much less than would be required for warm-blood animals of equal bulk,^ and their temperature is veiy little above that of the surrounding medium. When breathing free atmospheric air, they do not consume more oxygen than in theii* native element. Fishes absorb oxygen and exhale carbonic acid, not merely Avith their gills but with the whole surface of their body, as long as they are surrounded with water impregnated with at- mospheric air. This fact was proved by Humboldt in the fol- lowing manner. He passed a cork collar, covered with waxed cloth, over the head of a fish, which Avas then introduced into a vessel filled with water, the vessel being closed by the cork collar, which was so adjusted that the head and gills of the fish did not come in contact with the water in the vessel. Fishes thus treated lived five horn's, and the water in the vessel under- went the changes usually produced by respiration. Ermann found that the air, in the swimming bladder of lake fish, is deprived of a considerable portion of its oxygen. Biot, on the contrary, found in the swimming bladder of those marine fishes that inhabit deep waters, more oxygen than nitrogen. Humboldt and Provenyal observed that after the removal of the swimming bladder fishes continued to absord oxygen, but that they did not form any carbonic acid; they regard it, how- ever, as doubtful whether this phenomenon is due to the pa- thological condition of the animal, or to the absence of the swimming-bladder. Insects can live for a long time under the receiver of the air-pump, in a very rarified atmosphere; if, however, their stig- ' Thierchemie, p. 140. * Treviranus estimates the amount at about 50^ less than warm-blood animals of equal bulk would consume. Ilis conclusions are based on the experiments referred to in the text. BLOOD. 139 mata be closed with oil, they speedily die. The researches of Scheele, Vauqueliu, and Hausmaim show that in the resph-a- tion of insects a portion of the oxygen of the atmospheric air is converted into carbonic acid. TrcAiranus has observed that the amount of oxygen which is taken up is frequently twice as great as is required for the production of the carbonic acid formed, and that insects always develop nitrogen. Thus a honey-bee, confined in an atmosphere of 272 cubic inches, consumed 13*5 of oxygen, while it only jdelded 8*3 of carbonic acid and 5-3 of nitrogen. The experiments of Spallanzani and Hausmann tend to prove that the changes produced by worms on the atmospheric air in which they are confined are similar to those effected by insects. On the metamorphosis of the Mood. All our conceptions of organic life are associated with the idea of continuous change of substance. A constant metamor- phosis is going on in the living blood, which, in fact, may be regarded as the most obvious manifestation of its vitality. When it ceases to undergo this metamorphosis, it dies ; indeed the very act of \dtal annihilation is attended with a change in the blood, which we regard as an indication of its plastic power. As, however, life in every manifestation of its varying forms is depen- dent on certain conditions, and cannot exist when they are in- fringed, so it is with the vitality of the blood ; for although there is doubtless an actual inherent power in the blood, it can no longer act when it is deprived of the condition requisite for its maintenance, namely, the reciprocal action of the organism. The blood is not the only portion of the body that undergoes this change ; every organ and tissue is subjected to a similar meta- morphosis, which is presented to us under the general phenomena of nutrition and consumption, (or waste,) and which is dependent on, and effected by, the blood alone ; but since the various tissues present a different chemical composition, and since the different organs separate different matters from the blood, it is obvious that they cannot all modify the cu'culating fluid in the same manner, but that the metamorphosis must vary in some degree with the influence of the nervous system. Two conditions are essentially requisite for the metamorphosis of the blood, namely, circulation 140 CIRCULATING FLUIDS: and respiration^ iuasmucli as, without them, the blood would not be brought in contact with the oxj^gen, which is necessary for the existence of life ; and the more completely these func- tions are discharged, the more perfectly will the due changes in the blood be effected ; if, on the contrary, the blood is de- tained in any part of the body, or cannot enter the sphere of at- mospheric action in the lungs, the metamorphosis can be only imperfectly effected. We know, from the investigations of Schwann and Reichert, that all the tissues of the animal body are composed of cells, and that nutrition and growth of the organs and tissues is conducted by the production of new cells, appropriate for each individual organ, developing themselves at every point where the substance from which they are formed, viz. the blood, is conveyed ; that these cells, by their organic formation, effect a change in the nutritious plasma, by appropriating from it matters homologous to themselves, and that the cells are finally consumed or dis- solved, as is obvious from the general phenomena of the circu- lation. The nutrition and consumption of the tissues of the animal body in the general process of life is, consequently, the product of the nutrition and consumption of the cells which constitute those tissues. Since the capillaries are distributed over every particle of each individual tissue, and since their walls are composed of cells, which can communicate and impart the plasma to the adjacent cells, the plasma can be universally dis- tributed, and the reciprocal action between it and the cells of the various organs ensured. In what manner the cells act upon the nutrient fluid we are not able to understand, but there can be little doubt that they, or (which amounts to the same thing) the organs and tissues which they constitute, prodvice adialytic, catalytic, or, as Schwann terms it, a metabolic change on the plasma of the blood. The products of these influences must necessarily consist of certain chemical compounds, formed in very different ways, and var}' ing in their nature in accordance with the activity of the nervous power. The high atomic numbers of those animal substances which are of the most importance in nutrition, as the protein-compounds and fats, render the existence of numerous decompositions ex- tremely probable. In vegetable chemistry we find whole classes of substances transmutable, one into the other, in which the BLOOD. 141 same radical, consisting of carbon and hydrogen, is combined with different atoms of Avatcr, or of Avater and oxygen ; I need only refer to woody fibre,' starch, gum, sugar, and lactic acid. We have sufficient grounds for assuming the existence of simi- lar radicals in the chemical compounds of the animal body; and if we knew more of the composition of the extractive matters, we should doubtless find a radical common to all of them. In many of these decompositions, which are extremely varying in their nature, oxygen is undoubtedly absorbed, and carbonic acid evolved, as indeed we see in the process of respiration. Oxygen combines not merely with carbon ; it may also enter into combination with hydrogen and form water, or with a bi- nary or ternary radical, which it would oxidize. Hydrogen and oxygen may, further, be either separated from or taken up by these compounds, in the proportions in which they form water. Thus quaternary compounds may be split into several quaternaries with the same or a different radical, or into quater- nary and ternary compounds, &c. These must, however, be re- garded as mere possibilities, which, unless kept in check by experiment, are capable of indeterminate extension. One of the most important conditions for the reciprocal ac- tion between the cells of organs and the nutrient fluid is a proper degree of warmth ; the requisite temperature A-aries in difl'erent classes of animals, but its range is limited within very narrow bounds, above or below which the action is im- peded, or even destroyed, and death then ensues. If, there- fore, we should regard the conditions of temperature as inde- pendent of the organism, and unconnected with the phenomena of life, these phenomena would be unavoidably and perpe- tually disturbed, and the due course of the organism altogether destroyed. The conditions for the production of a due temperature are therefore based on the vital phenomena themselves, and in ac- cordance with the principles of adaptation that are obsen'ed ' [Woody fibre (lignine) . C,^ H, 0^ = (C,^ HJ O^ Starch .... C,, n,oO,o =(0,^ H^) 0^ + 2II0 Gum C,jH„0,, =(C„H,)08 + 3nO Cane sugar . . . C,, H,„ O.^ + H0 = (C,^ H,) 0, + 3110 Grape or diabetic sugar . C.^ H,i 0,, + 3H0 = (C,-, HJ 0^ + 6H0 2 eq. Lactic acid . . C,, H,„ 0.„ + 2H0 = (C,., H,) 0^ + 4H0.] 142 CIRCULATING FLUIDS in tlie animal organism, it is developed by those very processes for Avliich its existence is indispensably necessary. On animal heat. The temperature of every animal is higher than that of the surrounding medium. The temperature of the human body in those internal parts which are most easily accessible, such as the mouth and rectum, is usually between 97°' 7 and 98°-6. The temperatiu-e of human blood varies from 100°-6 to 101°-75 in a state of health, but in disease it may rise to 106° or 107°. In morbus coendeus and in cholera the temperature falls consider- ably : in the former the hand could only raise the thermometer to 78°-8, and in the latter, tlie heat of the mouth raised it only to 78°-8, and in another experiment to 77°. In healthy persons the temperature is said to attain its maximum during the day, and to fall from 1*8 to 2*7 degrees during sleep. In warm cli- mates Dr. Da\y found the temperatiu'e of the interior of the body 2°"7-3°*6 higher than in temperate climates. Tiedemann^ has given the following table regarding the tem- perature of birds, which is higher than that of any other class of animals. Great titmouse Degrees. . 111-25 Swallow .... . 111-25 Fringilla, different species 111-25 to 107 Anas, different species 111 to 106 Common hen 109-94 to 102-99 Falco, different species . 109-74 to 104-5 Pigeon ...... 109-58 to 106-7 Raven ..... 109-23 to 105-99 Vulture .... 107-49 Common cock 103-78 to 102-99 White game 102 Gull 100 Tiedemann and Rudolphi have also made an extensive series of observations regarding the temperature of the mammalia. The following is derived from their tables : Degrees. Bat (Vespertilio pipistrellus) . . 106 to 105 Squirrel 105 Sheep 104 to 100-4 ' Tiedemann's Physiologic, vol. 1, p. 454. BLOOD. 143 Degrees. Ox 104 to 99 Rabbit 104 to 99-46 Ape (Simia aigula) . . . 103-86 Cat 103-6 to 98-6 Bat (Vespertilio noctula) . .102 Dog 101-3 to 99-3 Guinea-pig 100-4 to 96-37 Hare 100 Elephant 99-25 Horse 98-24 to 97 There is no very great difference between the cetacea and the other mammalia in respect to their temperature. The tempe- rature of the seal and of the Greenland whale has been deter- mined at 104?°, and that of the porpoise has been found to vary from 99°-5 to 95°-9. The temperature of the amphibia differs very slightly from that of the sun'ounding medium. Czermack^ found that the temperature of a proteus was 63-5° when that of the air was o5°-4, was 68°-25 when the temperature of the air was 63°- 5, and was 65° in water at 55° ; in water of which the temperature was 44°-4, the temperature of a frog was 48°. Dr. Da\y found the temperature of a snake 88°-46 in air of 81°-5, and 90° in air of 82°-94 ; the temperature of testudo midas was 84°, while that of the air was 79°' 5. The temperature of fishes appears, from the experiments of John Hunter, Dr. Daw, Broussinet, and others, to be from "7 to 2*7 degrees above that of the surrounding water.^ It must be regarded as an established fact, that a certain temperature is necessary for the continuance of animal life, and that the source of this temperature must be sought for within the organism, and must be looked upon as a consequence of life itself. The production of heat cannot, how^ever, be so properly ascribed to any of the collective phenomena of life, as to the chemical processes, which are known to develop Avarmth, and the action of which we see in the metamorphoses ; and on ' Baumgartner's und Ettiughausen's Zeitschrift fiir Physik und Mathematik, vol. 3, p. 385. * [The theory of respiration, as the source of animal heat, invented by Lavoisier and Laplace, as well as the critical experiments by which that theory was tested by Dulong and Despretz, are too well known to require repetition ; neither need we devote any space to the influence of the nerves on the generation of heat. The sub- ject is fully discussed in Miiller's Physiologj, translated by Dr. Baly, vol. 1, pp. 83-88 ; first edition.] 144 CIRCULATING FLUIDS: the other hand a certain degree of animal heat is indispensably requisite for those chemical processes which are the necessary consequences of the proper organic development of the cells of all tissues, and of their catalytic influence on the nutrient fluid, the plasma of the blood. The animal heat is therefore to be regarded as the product of those vital functions, for the due exercise of which it is essentially requisite. The organism is thus protected against the innumerable disturbing forces under which it would otherwise succumb, in consequence of the vary- ing temperature of the external world. The development of heat, therefore, decreases with the diminution of the vital powers, with the retarded circulation of the blood, with checked nutrition, and with imperfect metamorphosis, while all the phenomena of inanition, perfect destruction of power, and finally an asphyxiated condition, are the consequences. As this cellular action, which is collectively exhibited in the metamorphosis of the animal organism, may be regarded as purely chemical, so the heat that is engendered thereby may be considered as a consequence of these chemical processes, and therefore all those functions of the organism which are necessary for the preservation of life, contribute directly or indirectly to the production of animal heat, Avhich must be regarded as de- veloped at every point at which metamorphosis is occurring, and therefore not merely in the lungs, but in the whole peripheral system. The absorption of oxygen, and its combination with the carbon of animal matter, not only in the lungs, but in the whole body, must, on that account, be regarded as the prin- cipal source of heat. In addition to the oxygen required for the formation of the carbonic acid, a certain amount is ab- sorbed, Avhich probably enters into combination with hydrogen, or with binary or ternary radicals of carbon and hydrogen, of carbon and nitrogen, or of carbon, hydrogen, and nitrogen, and in this manner, doubtless, contributes somewhat to the general production of heat. The theory of animal heat affords a simple explanation of many well-known phenomena, as, for instance, of the slight inde- pendent warmth of the foetus, Avhen removed from the uterus (as shown by Autenrieth and Schultz),^ and of those young ' Experimenta circa calorem fcetus et sunguinein. Tub. 1 799. BLOOD. 145 animals that are born in an imperfectly developed con- dition. The low temperature of persons with morbus coerulcus, in whom the metamorphosis of the blood is alwaj^s imperfect^ and the corresponding phenomena that arc presented by aged, debiHtated, sick persons, and those in whom (according to Edwards) a small quantity of blood cii'culates torpidly; as well as the increased temperature in inflammatory diseases when the blood circulates more rapidly than usual, and the metamorphosis is more rapid, are other illustrations of the same principle. The phenomena observed in hybernating animals are strongly corroborative of the mutual dependence of the animal heat and of metamorphosis, and also of the intimate connexion of the former with the processes of respiration and circulation. The observations of Pallas, Spallanzani, Mangili, Saissy, Czermack, and Berthold show that hybernation is prevented by a temperatm'c of from 50° to 80°, whilst it is induced in those animals that are subject to it, even in summer, by means of arti- ficial cold : other observers, however, maintain, that there is a periodical deficiency of vital energy at the usual hybernating season. During this peculiar state the respiration becomes slow, and may even cease altogether ; the circulation is likewise almost stopped, for Saissy found that the capillaries of the exter- nal parts of the body were nearly empty, while the larger ves- sels were only half filled, and the undulatory motion of the blood was observable only in the principal trunks of the thorax and abdomen. He likewise found that the blood did not contain the usual amoimt of fibrin and albumen at this period, and that the bile had a peculiarly sweet taste. The production of heat is also dependent on the mass of the blood- corpuscles, and on the rapidity of the cii'culation, — a view that perfectly accords with the preceding statement, for the corpuscles are (as we shall presently show) undergoing a constant metamorphosis, which may be regarded as an evidence of the \dtality of the blood, and which is intimately connected with the respiratory process. When there is a paucity of corpuscles, the necessity for the absorption of oxygen is diminished in a corresponding ratio, the circulation becomes slower, and there is less heat developed than in the normal state : on the other hand, blood with an 10 146 CIRCULATING FLUIDS excess of corpuscles^ but which is circulated slowly, develops less heat than blood which contains a smaller proportion of corpuscles, but which is more rapidly circulated, for more oxygen may be consumed in the latter than in the former case. The following table, drawn up from the researches of Dumas and Prevost, and amplified by my own observations, affords some interesting data on this point : Animal. Blood-cor- puscles. Mean tem- perature. Pulse. Respiration Pigeon . 15-57 107-6 136 34 Common hen . 15-71 106-7 140 30 Duck 15-01 108-5 110 21 Raven 14-66 108-5 110 21 Heron 13-26 111-2 200 22 Ape (Simla Callitriche) 14-61 95-9 90 30 Man 12-92 98-6 72 18 Guinea-pig 12-80 100-4 140 36 Dog . . . 12-38 99-4 90 28 Cat ... 1204 101-3 100 24 Goat 10-20 102-5 84 24 Hare 9-38 100-4 120 36 Horse 9-20 98-2 56 16 Sheep 9-20 100-4 Ox ... 10-50 99-5 38 Carp 2-10 51-1 to 51-4 20 Tench . 1-40 52-8 to 51-4 Green toad 2-20 51-8 to 51-4 77 The metamorphosis of the blood, and the general change of matter, lead to still another secondary source of animal heat. It has been shown by PouUet^ that all soHd bodies, organic and inorganic, undergo an elevation of temperature when moistened with different fluids. In organic substances it may amount to from 11° to 18°. Since the act of metamorphosis is always effected through humid membranes, this source of heat must be regarded as of great importance, even if it be not actually identical Avith the catalytic metamorphosis of the cells themselves. Becquerel and Breschet^ have observed, by means of a thermo-electric multiplier, that each contraction of a muscle is accompanied by an increase of temperatiu'e, amounting to ' Annales de Chimie et de Physique, vol. 20, p. 141. ^ Annal. des Scienc. Nat. 1835. BLOOD. 14/ from 1°'8 to 2°-6, the increased temperature that succeeds violent exercise may probably be in part accounted for by this means. Metamorphosis of the blood in the nutrition of the organism. The conveyance of nutriment to the various parts of the organism is one of the most important functions of the blood ; and in order to discharge it efficiently, the blood must itself receive a constant supply of proper material. Regarding the blood physically, as composed of corpuscles and plasma, it is only from the latter that the organs can di- rectly obtain nourishment. This plasma is, however, a very complicated fluid; its principal constituents are albumen, fibrin, fatty compounds, salts, extractive matters, and a pe- culiar colouring matter, hsemaphsein. The question now arises, Are all these constituents, or only some of them, employed in nutrition? Our analyses of m-ine, sweat, and mucus show that these secretions and excretions carry oif, in addition to certain peculiar matters, the same pigment, the same salts, and the same (or similar) extractive matters as are contained in the plasma ; hence we may infer that those substances which are removed from the body are eff'ete products of the metamorphosis, and that they are not suited for nutriment, at any rate in the form in which they occur. Neither albumen, fibrin, nor fati is found in urine, sweat, or mucus, and the presence of either albumen or fat is always regarded as a symptom of a morbid state. This fact tends to support the opinion that albumen, fibrin, and fat are the substances which are employed in the nutrition of the peripheral system. The blood, in its passage through the capillaiy network, permeates all organs and tissues, and their cells take up from the plasma those substances which they requii'e for nutrition, and restore to it those which have become eff'ete, and are no longer adapted for the process of nutrition. We may con- ' The fat that is occasionally to be detected in the sweat does not arise from the true perspiration, but fi-om the sebaceous glands of the skin. Perfectly normal mucus, such as occurs in some quantity in healthy urine, contains neither albumen nor fat. Pulmonary mucus and the saliva discharged with it often contain a little fat and albumen, but, in all probability, they belong to the saliva only, a fluid not intended to be excreted. 148 CIRCULATING FLUIDS: elude that the act of nutrition is effected by the sole influence of a vital power inherent in the cells, and that the plasma is entirely passive. If the various tissues of the animal body, different as they are in their chemical constitution, obtain their nourishment from the protein- and fat-compounds of the plasma (which contains the elements of the cells, but not the diff'erent cellular substances themselves,) it is clear that the cells and tissues must produce a metamorphic effect on that portion of the nutriment which is homologous with themselves. Their catalytic, or as Schwann 2, in his theory of cells, terms it, their metabolic power, evolves from the plasma the materials that serve for the nutrition of the cells. The plasma is here the cyto- blastema, the catalytic or metabolic force lies in the cells and tissues. But although the plasma acts only passively in this nutritive process, we cannot deny it a peculiar vital power. This is first manifested in the formation of the cytoblastema, for the force that creates these forms cannot be regarded as inde- pendent of the plasma. If the nucleus is formed by the so- lidification of fibrin in the plasma, Avhicli from the similarity of their constitution is probable, its formation must be re- garded as the result of a purely plastic force in the liquor san- guinis. If, however, all the different portions of the body, — the muscles, bones, cartilages, horny matter, serous mem- branes, sinews, neurilema, brain, &c., — are nourished and formed by the protein- and fat-compounds of the plasma, we must arrange these compounds into those which are, and those which are not, homologous to the tissues. Neither albumen, fibrin, nor fat can belong to the second division, since the tissues are formed from these substances. I have already mentioned, that those constituents of the plasma, that are excreted in the urine and the SAveat, cannot reasonably be considered as any longer nutritious, for it would be at variance with our ideas of a consistent organization to suppose that substances which could be subservient to the pre- servation of the body should be removed from it ; it would be just as irrational to conceive that they were conveyed into the body in order to cii'culate therein, with the nutriment, with no definite object; it only remains then for us to conclude that ' Mikroskopische Untersuchungen, p. 231 and 234. BLOOD. 149 they are formed in the body, and in that case they can only be regarded as products of metamorphosis. The most important constituents of the secretions and excretions separated from the blood are urea, uric acid, bilin, haemaphaein, biliphaein, ex- tractive matters, lactic acid, salts, and mucus. ]\Iucus must not, however, be regarded as a genuine excretion, for it plays an important part in the animal organism, and its removal is not a matter of vital necessity, but the urea, uric acid, and bilin are chemical combinations which, in a healthy condi- tion of the system, are removed by certain organs in a fixed quantity, but which are not met with in the blood itself: and, indeed, it is difficult to understand how these products of the metamorphosis of the plasma (constant in their amount, and determinate in their composition) are produced in the formation of tissues, which present entirely different chemical characters, and which are frequently developed in very changeable pro- portions. It seems more rational to conceive that the urea, uric acid, and bilin are products of the metamorphosis of a sub- stance of a fixed chemical composition, which, by the simplicity and uniformity of the changes to which it is subjected, gives origin to the formation of these products of decomposition. We shall revert to this subject in om* observations on the me- tamorphosis of the blood-corpuscles, and on the manner in which the production of hsemaphsein may be explained. There still remain for oui' consideration the extractive mat- ters, the lactic acid of the urine, and the salts : all these sub- stances occur in no inconsiderable quantity in the blood, and their formation during the act of nutrition of the various tissues is consequently very probable. If the various tissues are formed from the plasma of the blood, and if, as is probably the case, their formation is accompanied by the absorption of oxygen and the liberation of carbon, the resulting products may be ex- tremely various : indeed there are so many different forms of extractive matter, of the true nature of which Ave are still ig- norant, that we are justified in the conclusion, that they un- dergo very complicated transformations during the nutrition of the tissues. While all the tissues may be considered as albu- minous, gelatinous, osseous, horny, or fatty, it mnst be re- membered that the various fats differ materially in their con- stitution, and that there are similar differences amongst the 150 CIRCULATING FLUIDS: albuminous tissues. If we regard the extractive matters as the products of the nutrition and waste of the different tissues, the variety in which they exhibit themselves is not at variance with the conceptions we are led to form respecting the nature of metamorphosis. Another circumstance in support of this view is, that the formation of similar matters is observed in the vegetable kingdom, where there is a vital, reciprocal action be- tween the cells and the nutriment, combined either with the production of lactic, or of some allied acid. Although these extractive matters are, vrithout doubt, entirely different from those that occur in the animal body, they correspond in many of then- physical and chemical properties : both are inca- pable of being exhibited in a crystalline form, they dissolve readily in water and partially in alcohol, they are precipitated by many of the metallic oxides, and it is a matter of extreme difficulty to obtain them in a state of purity in consequence of their tendency to undergo transformation and to become che- mically changed. Until the extractive matters of the animal body have been accurately analysed, and the composition of the various tissues has been determined, it will be impossible to obtain a rational insight into the nature of these changes. It appears from the statements of Berzelius, as well as from my own investigations, that some of the extractive matters which occur in the blood and in the flesh are also met with in the urine. It still remains to be decided whether all the ex- tractive matters of the flesh pass unchanged into the blood and are thrown off" by the urine, or whether they become changed in their passage ; or, lastly, whether they are not partially me- tamorphosed in certain organs, and again rendered fit to serve the purposes of nutrition. When we consider the Avisdom that is universally obvious in the economy of the animal body, it seems probable that the last is the most correct view, and it is by no means improbaljle that the gelatinous tissues are sus- tained by a cytoblastema, allied to the extractive matters. The fact that some of the extractive matters of flesh are not only strengthening but \evy digestible, renders it more than probable that some of the matters of this class serve as nou- rishment; while others, incompatible with the purposes of nu- trition, are excreted. BLOOD. 151 The plasma of the blood contains salts, some of which arc pe- culiar to that fluid, and are transmitted from thence into the se- cretions and excretions, while others (especially the phosphates of lime and magnesia, fluoride of calcium, together with small quan- tities of the sulphates and carbonates of soda and lime), occur in the bones as actual constituents of the body. The latter are con- veyed into the body with the food, partly in the state of phos- phates, &c., while their formation is also in part due to the pro- duction of phosphoric and sulphuric acids by oxydation of the phosphorus and sulphur which occur in the protein-compounds, and the subsequent combination of those acids with bases. These salts are again found in the urine, for they are removed by the blood during the metamorphosis of the bones, and are excreted by the kidneys. In the present state of our chemical knowledge, it is impossible to assign with certainty any de- finite function, to the large quantity of salts, which enters the blood but is not transferred into any of the solid textures of the body. Hewson suggested that the object of the saline con- stituents of the serum was to enable the blood-corpuscles to retain their discoid form. Albumen^ without salts, has as little power as pure water in hindering the solution of the blood- corpuscles. Hewson^s view seems to be supported by the facts, that the alkaline salts which occur in only a very slight pro- portion in solid textm'es, are found in a very large quantity in the blood ; and further, that when water is mixed with blood, by injection into a vein, in a sufficiently large quantity to dis- solve or modify the form of the corpuscles, a fatal result ensues. As these salts are continuously introduced into the blood with the food, a corresponding amount must be removed by the ex- cretions. The salts have, however, other functions than that assigned to them by Hewson. The blood, as is well known, has always an alkaline reaction, and it might therefore be sup- posed that if a large quantity of an acid were taken, the reaction of the blood would be neutralized. This is, however, by no means the case, partly because only a certain quantity of the acid enters the blood, the remainder being carried off by the intestinal canal, and partly because the portion that does enter the circulating fluid is at once removed by the kidneys. Thus all the mineral acids may be detected in the urine after their administration ; the vegetable acids appear, however, to undergo 152 CIRCULATING FLUIDS : a partial change, at least Wohler found that neutral potash, or soda salts, formed by a vegetable acid, were decomposed in the organism, and that the bases were removed by the urine in the form of carbonates. We thus see that the existence of basic salts in the blood is indispensably necessary; and as neutral or acid salts are usually contained in the food, it is clear that they must undergo such a change in the body as to permit of the removal of the acids by the urine while the bases are retained. There is every reason to suppose that the basic salts of pot- ash and soda in the blood serve for the purpose of combining with the lactic, fatty, uric, and probably carbonic acids that are continually secreted diu-ing metamorphosis. The salts of lactic and uric acid are in part excreted in that form; and in part, as has been remarked, are decomposed, so that the free acids are separated by the kidneys, while the bases are retained. The salts of the fatty acids appear to be secreted only in the hver. "Whether chloride of sodium, which appears to be requisite for all the mammalia, serves merely for the purpose of preventing the solution of the blood-corpuscles, or whether it does not, like some other salts, act as a stimulant on the nerves, and in that manner influence the composition of the blood, is a question not easily answered. Active metamorj^hosis of the blood. As the plasma is subjected to a continuous change in the peripheral system during the nutrition of the tissues, it becomes a matter of necessity, that it should also receive a continuous supply. This is afforded to it by the chyle, a fluid generally only poorly supplied with blood-corpuscles, but abounding (at least at certain times) in lymph- and chyle-corpuscles, and oil- vesicles, and containing some fibriiv. The chyle is therefore not blood, although closely allied to it ; if, however, as is generally believed, the chyle is the only nutriment of the blood, it must ultimately be changed into blood, and this transformation is eff'ected by an increase of the blood-corpuscles, and by a dimi- nution of the lymph-, chyle-, and fat-corpuscles, while the fibrin is not only increased, but becomes more plastic. A change must therefore take place in the blood itself, and this must be not of a passive nature, as during nutrition in the peripheral system, but active ; we must assume tliat there is a formation and de- BLOOD. 153 velopment of certain substances in the blood, produced by a certain ^ital power inherent in this fluid, with the aid of neces- sary potential forces, as, for instance, of oxygen. This change or metamorphosis represents the real vitality of the blood, and, as far as Ave at present understand it, we may describe it as a process in which not only blood-corpuscles are formed, (by a consumption of lymph-, cln'le-, and fat-globules,) and fibrin is produced, but further, in which the blood-corpuscles are again consumed ; for it is obvious that if there is a continuous process of formation while their total number remains nearly constant, there must be a corresponding consumption of them. The presence of atmospheric oxygen is indispensably re- quisite for this active metamorphosis of the blood, and one of the results of this change is an excretion of carbon, which com- bines Avith a portion of the absorbed oxygen, so as to develop a certain degree of warmth. The probability that the chemical process, which occui's during nutrition in the peripheral system by means of the plasma, involves the absorption of oxygen, has been already noticed. The importance of the presence of oxygen for the perfect metamorphosis of the blood, and indeed for life itself, is sufficiently obvious from the circumstance that the ces- sation of the respiratory process is followed by immediate death. Although the respiratory process is as necessary for the active metamorphosis of the blood as for the production of animal heat, yet neither of these processes is to be referred to the lungs alone, but to the whole peripheral system. If it were other- wise, the temperature of the lungs would be much higher than it actually is ; whereas, in reality the excess of temperature of those organs is very slight, and may probably be sufficiently accounted for by the more energetic action of the atmospheric oxygen on the mass of the blood in these organs than in other parts of the body. I cannot give any description of the manner in which the blood-corpuscles are formed from the consumption of honph-, chyle-, and fat-corpuscles. Physiologists suppose that a capsule, which at first is very thin, but subsequently becomes thicker and thicker, is developed around the h-mph-coq^uscle : this cap- sule is filled with hsematoglobuhn, which at fij'st is compara- tively colourless, but subsequently assumes a Aind red tint. We are perfectly unable to state Avhere the first haematoglobulin 154 CIRCULATING FLUIDS: is formed, but there is no doubt that the respiratory process is essential to its production. Schultz and Henle have examined the blood-corpuscles in their various stages of development, and have arrived at very similar conclusions. Schultz' observed that the young corpus- cles were poorer in colouring matter than the older ones, and that, consequently, the nucleus was much more distinct. The capsule becomes tumid in proportion to the age and development of the blood-corpuscle, whilst the nucleus becomes gradually smaller, and in some cases entirely disappears. Water acts very difierently on blood-corpuscles in different stages of develop- ment. The younger and more delicate blood-corpuscles are quickly and readily dilated by a very small quantity of water ; they are soon entirely deprived of their colouring matter, and become perfectly clear and transparent ; whilst the older and more developed corpuscles entirely resist the action of water, or at the most only become rounded, and do not dissolve except on the addition of a large quantity of water. They remarked at the same time that the corpuscles most abundant in coloiu*- ing matter frequently presented a minute nucleus up to their final disappearance ; while many of the most highly developed ones gave no indications whatever of a nucleus. That a metamorphosis of the blood-corpuscles does occur can- not be for a moment doubted, but with respect to the peculiar circumstances under which it is conducted, and to the products that are then formed, we know scarcely anything : all that we have been able to ascertain with any degree of certainty is, that oxygen is absorbed, and carbon given off during the process ; and the following facts justify us in this conclusion : a. Dark blood, both within the system and out of it, as- sumes a lively reddish tint on being brought in contact with oxygen. This change is probably based on a chemical change in the hsematin. b. Blood taken from the body and agitated with oxygen absorbs a certain portion of the gas, while carbonic acid is formed. The mere serum, however, which contains no blood- corpuscles, absorbs only a very little oxygen, and develops car- bonic acid in a corresponding ratio. ' Ueber die gehemmte und gesteigerte Auflosuug und Ausscheidiuig der verbrauch- teu Bliitblaschen. Hufeland's Journal, 1838. BLOOD. 155 c. The consumption of oxygen and the formation of carbonic acid stand in a direct ratio with the amount of ])lood-corpusclcs, and with the number of respirations in a given period. Hence it is obvious that the oxygen taken up by the blood dimng the respiratory process^ is, for the most part, consumed in the metamorphosis of the corpnscles.i The development of the blood-corpuscles is doubtless con- ducted on the same principle as that of other cells ; i. e. the blood-corpuscles exert a transforming influence on the surround- ing plasma ; they select from it the materials requisite for their development, and reject the non-homologous products that are formed in it. Amongst the matters that are taken up there must be always free oxygen. During the later stages of development of the blood-corpus- ' [There are two rival theories respecting the manner in which oxygen is taken up by the blood and conveyed to the peripheral system. Liebig maintains that this is effected solely by the iron in the corpuscles, while Mulder refers it entirely to tlie oxi- dation of protein-compounds. Liebig asserts that the coqjuscles of arterial blood con- tain peroxide of u-on ; that, in their passage through the capillaries, they lose a portion of their oxygen and combine with carbonic acid, so that, in the venous system, they no longer contain peroxide, but carbonate of the protoxide of iron. WTien they reach the lungs, an exchange takes place between the carbonic acid of the blood and the oxygen of the atmosphere. Mulder, on the other hand, denies that the blood -cor- puscles are conveyers of oxygen, and that iron is oxidized during respiration, as assumed by Liebig, and he found his conclusions on the following grounds ; a. The iron is so intimately connected with the other elements of hasmatin that it cannot be removed, even by long digestion of this constituent in (Ulute hydrochlo- ric or sulphuric acid. (Vide supra, p. 41.) Consequently it is highly improbaljle that it should be oxidized in the lungs. Liebig, indeed, observes that dilute acids remove iron from dried blood, but Mulder gets over this difficulty by showing that other constituents of the blood, besides the colouring matter, contain this metal, apparently in an oxidized state. /3. If, as Liebig asserts, peroxide of iron exists in arterial, and cai-bonate of prot- oxide of iron in venous blood, almost any dUute acid would be capable of extracting the oxide, which we have shown not to be the case. y. Assuming, with Liebig, that the iron exists in arterial blood as a peroxide, the organic part of hsematin would be different ; instead of being C^^ Yi.,., N^ Og, it would be 2 (C^ H,., N, Og Fe) — Fe, 0^, or 2 (C^, H,, N3 O^.j). S. The probabiUty of its existence in a metalUc state has been already shown. (Vide supra, p. 42.) «. The amount of haematin in the whole mass of the blood is far too inconside- rable to carry a due supply of oxygen to the W'hole system. Mulder's theory has been alluded to in an early part of this work. (Vide supra, p. 12, note.) We shall have occasion to notice it at some length in our obser\'ations on the differences between arterial and venous blood.] 156 CIRCULATING FLUIDS : cles up to their jfinal solution^ they must undergo so thorough a change as to leave no remains of their principal constituents, the hsematoglobulin, the nuclei, and the capsules, for not a trace of these substances, is found either in the plasma or in any of the secreted or excreted fluids, in which we should naturally expect to find them. It is altogether impossible to state how this change takes place ; this, however, is evident, that if the metamorphosis of the blood-corpuscles terminates in their per- fect solution, both the capsule and the nucleus must be en- tirely dissolved, and neither hsematin nor globulin can be contained in it at the moment of solution. What the products of this change actually are is very difficult to determine with any degree of certainty. Transitory combinations with a brief existence may be pro- duced, or compounds may be formed, which undergo a further decomposition in certain organs. It is very probable that substances closely resembling the extractive matters are formed in the metamorphosis of the blood-corpuscles, by the decom- position of which urea or uric acid are produced, so that by the influence of a certain organ (the kidney) the compound is separated into those substances, and another form of extractive matter. It may further be presumed that the composition of hsemaphsein is such as to include the constituents of biliphsein, and that the hepatic cells possess the power of secreting the biliphsein from it. Combinations may likewise be formed of which we know actually nothing; for the blood has not yet been sufficiently examined. These points need not engross our consideration at present; and I will only remark, that in my attempt to prove that the fibrin and hsemaphsein of the plasma, the urea, uric acid, bilin and its acids, the biliphsein, and certain acid fats, are products of the metamorphosis of the blood- corpuscles, I by no means conclude that they are the only products ; in fact, I freely grant ray assent to the possibility of many others. The blood contains a certain amount of fibrin, varying from '2 to '9, or according to Andral even to 1*02, which on whipping is separated in thickish, globular, elastic, stringy masses; the chyle appears from my analyses to contain not more than from '03 to '04^ of fibrin, which, in consequence of its slight tenacity separates on whipping into loose and BLOOD. 157 globular, or else into flocculcnt mucous masses. Fibrin is tberefore obviously formed in the active metamorphosis of the blood; and that portion which preexists in the chyle is modi- fied and rendered more plastic. It is a well-known fact that the respiratory process not only increases the plasticity of fibrin in the blood, but also its quantity, and that on the other hand the amount of fibrin diminishes in blood which is not efficiently brought in contact with oxygen. As the blood-corpuscles principally consume oxygen during their change, it appears very probable that the fibrin is produced during this process. This view is elucidated, and I may say confirmed, by my analyses of the blood, in which it appears that with very few exceptions, the amount of fibinn always varies inversely with the mass of the blood-corpuscles, or, in other words, that the more corpuscles there are, the less in quantity is the fibrin, and vice versa. This fact is readily explained by the adoption of the view that fibrin is formed from the blood-corpuscles ; for it is obvious that the quantity of fibrin in the plasma must in- crease during an extraordinary consumption of the corpuscles. Let us now inquire which of the constituents of the blood- corpuscles has been employed in the production of that most essential ingredient of the plasma, the fibrin ? It can hardly be the globulin, for that forms from 4 to lOj] of the blood, and, being a protein-compound, is so intimately connected in its chemical relations to fibrin, that if we were to suppose that it were converted into fibrin, we should expect to meet with a much greater quantity of this latter constituent in the blood than we find actually existing ; still less can it be the hsematin ; indeed, the use of this appears to be to facilitate and to maintain the independent metamorphosis of the blood-corpuscles, through its energetic capacity for the absorption of oxygen, and through its own metamorphosis, instead of forming a product for the further nutrition of the plasma. The capsules and the nuclei still remain for consideration. Of the former we know very little, but the latter actually possess chemical characters which approximate them to fibrin, so that there is no impediment to the supposition that this important constituent of the blood is formed from the nuclei by a metamorphic process, accompanied probably by the absorption of oxygen and the separation of carbon. 158 CIRCULATING FLUIDS : The nuclei may be distinctly seen in young blood-corpus- cles, but in the process of development they become smaller, and, according to Schultz and Henle, as the final solution of the blood-corpuscles approaches, they altogether disappear; hence the metamorphosis of the nuclei is by no means sudden, but progresses with the development of the blood-corpuscles. Burdach,^ K,. Wagner,^ and Valentin^ are of opinion, that as long as the blood-corpuscles cu'culate in the Hving body, they possess no nucleus, and that this is only formed at the instant that the blood-corpuscle is removed from the circulation. R. Wagner found that nuclei were formed by the mere con- tact of the blood-corpuscles with atmospheric air. This is a further point of analogy between the nuclei and the fibrin of the plasma; and if we could only succeed in observing the unequivocal reappearance of a nucleus in a blood-corpuscle removed from the body, and in which, on account of its ad- vanced development, the nucleus had undergone solution, we might then, in my opinion, consider that the change of the nuclei into fibrin was sufficiently established, especially when we reflect that no other constituent of the blood possesses the extremely characteristic property of being retained in solution in living blood, and of separating into an insoluble mass as soon as the vitality of the fluid is destroyed. If we assume that the fibrin is formed in this manner, it follows that the amount of fibrin must always stand in an in- verse ratio to that of the blood-corpuscles ; and this is in reality the case, — that whenever the activity of the metamorphosis is increased, the amount of fibrin must likewise increase ; and further, that whenever the blood is hindered in its circulation, or its supply of oxygen is stopped or lessened, the amount of fibrin must diminish. All these consequences really take place. Blood that stagnates in the vessels loses fibrin, for it is consumed, while no fresh supply can be formed. Menstrual blood, and the blood in melsena contain no fibrin;* and I shall subsequently refer to other similar cases. ' Physiologic, vol. 4, pp. 27 and 94. ^ Beitriige zur vergleichenden Physiologic des Blutes, 1838, p. 14. ^ Haudbuch der Entv\'ickeliingsgeschiclite des Menschen, p. 296. ■* [That the menstnial discharge does occanionally contain fibrin will be shown in a future part of this work.] BLOOD. 159 Let us now proceed with tlie metamorphosis of the blood- corpuscles ; the next question for consideration is this : Jl'hat changes do the hcematin and globulin undergo ? It has been ah'cady sho^na that both these substances must undergo an entire change during the period of development of the blood- corpuscleSj that terminates in their consumption or solution. The plasma contains a peculiar colouring matter, hffimaphsein, to which it owes its yellowish colour/ and which cannot accu- mulate in it beyond a certain amount, because it is con- tinuously removed by the kidneys ; it is, in fact, this consti- tuent that gives the yellow or yellowish-brown tint to the urine. It can hardly be doubted that the hsemaphsein is a product of the metamorphosis of the hsematin ; especially, if it can be proved that it is formed solely from the blood-corpuscles, and that it is contained in them to a large amount. We can obtain from the serum o\\\j slight traces of hsemaphsein, but the clot yields a considerable amount of colouring matter, which must be therefore contained in the blood-corpuscles. The hsemaphsein is formed from the hsematin during the de- velopment of the blood-corpuscles, and the change is probably accompanied by an absorption of oxygen and a separation of carbon ; the youngest blood-corpuscles must consequently con- tain less hsemaphsein than those that are older ; and when the act of development terminates in theii* solution, they no longer possess any hsematin, but only hsemapha^in. In a normal state, the consumption and production of the blood -corpuscles must be nearly balanced, and consequently the proportion of the hsematin to the hsemaphajin will remain tolerably constant ; when the metamorphosis of the blood is accelerated (i. e. when the circulation is quickened, and the mutual action between the blood and oxygen is increased) more blood-corpuscles will be consumed in a given time than in the normal state, and the consumption will especially include the older ones which abound in colouring matter, and which in their development are approximating to the stage of solution. ' When the serum, after the separation of the clot, is of a reddish tint, which is not unfrequently the case, blood-corpuscles are suspended in it. In icterus the serum is often of a brownish red colour, in consequence of the presence of bihphaein ; in this case the colour rapidly changes into a green, on the addition of nitric acid. 160 CIRCULATING FLUIDS: In these cases there is^ therefore, not merely a diminution of the quantity of the blood-corpuscles, but likewise of the colouring matter contained therein, since the corpuscles that remain are young and deficient in colouring matter, containing, in addition to hsematin, only a very small quantity of hsemaphsein. If the cu'culation of the blood is impeded in any part of the body, and it is prevented from receiving its due supply of oxygen, the metamorphosis will likewise be impeded and rendered imperfect ; the matured blood-corpuscles Avhich are approaching the stage of solution will not be dissolved, and there will consequently be an accumulation of colouring matter, especially of hsema- phaein, which is the most abundant pigment in the matured corpuscles. All these appearances are actually observed. I shall be able to demonstrate that, in inflammatory affections, (when the me- tamorphosis of the blood is excited to increased activity in con- sequence of the accelerated circulation and the increased mutual action of the blood and oxygen,) there is only a small amount of colouring matter present in the blood, and that, in all pro- bability, heemaphsein constitutes but a minute portion of the little that does exist ; while, on the other hand, in blood which is retained in the body without being submitted to the due action of oxygen, in which the perfect metamorphosis is checked, and the corpuscles are not dissolved, as in melsena and in morbus maculosus, there is a great excess of hsemaphsein. The colouring matter may also accumulate when organs that take an active part in the metamorphosis of the blood are affected, as I have observed in morbus Brightii. I shall now proceed to show that it is much more probable that such substances as urea, uric acid, and bilin, which are definite compounds secreted in a nearly constant ratio by peculiar organs, should be products of the active metamorphosis of the blood-corpuscles, than that they should be formed during the metamorphosis of the plasma in connexion with the process of nutrition. It is but reasonable to infer that such substances as urea, uric acid, and bilin, which are separated in large quantity by the kidneys and liver from the blood, should be products of the metamorphosis of a substance of an invariably uniform compo- sition. In every class of animals, in the most varied forms of BLOOD. 161 existence, under tlie most opposite kinds of food, we find that the bile is a secretion of the liver; whilst amongst all the higher classes of animals and many of the lower, urea and uric acid, or one of the two, occur as a constant secretion of the kidney. 1 It seems opposed to all reason to imagine that in animals as difterent in structure as they are opposite in their habits of life, and under every possible variation of circum- stances, these fixed and definite compounds should be products of the metamorphosis of the plasma during the nutrition of every form of tissue. It is, however, easy to conceive that the corpuscles which, although different in their form, are similar, if not identical, in their chemical constitution, in the blood of all these animals, should, under similar conditions, yield similar products as the result of their metamorphosis, and that these products should take the form of urea, uric acid, and bilin. This consideration alone is deserving of much weight in sup- port of the view that I am now advocating. If the urea, uric acid, and bilin were formed in accordance with the other hypo- thesis, their production would be increased, diminished, or stopped, according as nutrition was proceeding favorably, was deficient, or was entirely checked, as happens in certain dis- orders. But it is well known that the production of these substances is by no means dependent on such circumstances. The secretion of urea, uric acid, and bile proceeds, both in man and animals, when the tissues are gradually Avasting from dis- ease, and when their nutrition is utterly suspended ; they are separated long after the body has ceased to take any food what- ever, in fact, as long as respiration and even life itself remains, the only necessary condition being the healthy state of the secreting organs. I have had several opportunities of examining the urine during inflammatory diseases, both before and during, or shortly after the height of the attack, and have found that, in the latter case, there was always a greater amount of lu-ea than in the former. This is easily explained by the conside- ration that the active metamorphosis of the blood-corpuscles is accelerated by an excited inflammatory state, and that, conse- quently, a larger number of the corpuscles is consumed during a given time, than in the ordinary condition of the system. ' MuUer's Handbucli tier Physiologic, vol. 1, pp. 515 and 588. 11 162 CIRCULATING FLUIDS : My analyses of tlie blood are even more confirmatory than any of the preceding statements, of the production of these substances during the active metamorphosis of the corpuscles. I analysed the blood of the aorta and vena renalis of one animal, and the blood of the vena portarum and vena hepatica of another animal, with the following results :^ 1. a. Blood of aorta, 6. Blood of vena renalis. in 1000 parts. in 1000 parts. Water . 790-000 778-000 Solid constituents . 210-000 222-000 Fibrin 8-200 p2 Albumen . 90-300 99-230 2. «. Blood of vena portarum. b. Blood of vena hepatica. Water . 738-000 725-000 Solid constituents . 262-000 275-000 Fibrin 3-500 2-500 Fat 1-968 1-560 Albumen . 114-636 130-000 Globulin . . 116-358 112-580 Haematin 4-920 4-420 Haemaphfein 1-467 1-040 Extractive matter 16-236 17160 Here we observe that the arterial blood contains more water than the blood of the renal vein, and that the blood of the vena portarum contains more than that of the vena hepatica ; the arterial blood and the blood of the vena portarum contain a larger amount of fibrin than the blood from the renal and hepatic veins respectively. The blood of the renal vein con- tains more albumen and fewer blood-corpuscles than arterial blood, and a similar relation holds good between the blood of the hepatic vein and of the vena portarum. Passing over all other points of difference, the results at which we have abeady arrived afford an a priori argument for, and a confirmation of, my theory respecting the formation of urea, uric acid, and bile, ' In tbe first analysis, the venous blood from both the renal veins was collected. The amount, although small, was sufficient for the required purpose. Professor Gurlt, of our veterinary school, had the kindness to obtain the blood for me. ^ The whole amount of blood from both renal veins did not exceed sixteen grains, a quantity not sufiiciently large to admit of the determination of the fibrin by whip- ping. I employed it in determining the ratio of the albumen to the dried residue, and found that while the aortic blood contained 43, the blood of the renal veins con- tained 44-7|j of albumen. BLOOD. 163 from the corpuscles during tlie active metamorphosis of the blood. Since the kidneys and the liver secrete fluids from the blood of less specific gravity than the blood itself, it is clear that in its passage through these organs it must become richer in solid constituents than before it entered them ; moreoverj as in its circulation through these organs it meets with no free oxygen, it must be poorer in fibrin when it leaves them than on its entrance. The change that the blood undergoes in these organs, is, however, by no means so simple as it might appear to be, and as, in fact, these analyses might lead us to conceive. There result from it the products of the metamorphosis of the cor- puscles, or of the compounds that are formed from them, as well as of the plasma, during the nutrition of these organs. The excess of albumen in the blood of the renal and hepatic veins is clearly opposed to the view that the urea and bilin are formed from the plasma. It is sufficiently established that the renal cells possess the power of removing an excess of salts and water from the blood, in the same manner as the hepatic cells separate fat. I beg expressly to repeat that I do not regard the urea, lu'ic acid, and biHn, as the only substances that are formed, besides fibrin and hsemaphsein, during the active metamorphosis of the blood-corpuscles; on the contrary, I am of opinion that other substances are like-^dse produced, regarding the formation of which we might speak with greater certainty if almost every- thing regarding them were not based on mere conjectures. It is, for instance, very probable that a portion of the globulin is converted into albumen, which, since both substances are protein-compounds, might happen in two ways, either by a portion of the phosphorus, or sulphur, being oxydised, if glo- bulin contain more of those elements than albumen ; or if, on the other hand, it contain less, by the globulin dividing into, for instance, one half or one third of a protein-compound with all the phosphorus and sulphur, and into one half or two thirds of a protein-compound devoid of phosphorus and sulphur, which then undergoes further metamorphosis. The fat, which is more abundant in the blood-corpuscles than in the serum, must likewise undergo a change. The fat of the serum appears to be softer than that of the corpuscles, while that of the fibrin is firm and 164 CIRCULATING FLUIDS: white. In all of them there is cholesterin, margaric and oleic acids. Berzelius could detect no phosphorus in the fat of fibrin ; neither did Lecanii find any in the fat of the serum. The fat containing phosphorus^ which Boudet found in the blood, must belong to the corpuscles. We cannot form any veiy clear idea of the manner in which these metamorphoses are conducted ; it is, however, probable that the phosphorized fats are conducted to the brain. Since the fats that are taken as food consist, for the most part, of stearin, raargarin, and olein, it would appear as if fatty acids were formed from them by a process of oxyda- tion during the succeeding formation of blood-corpuscles, and the consumption of IjTuph-, chyle-, and oil-globules. The elementary composition of many of the substances that are formed from the blood, and of some that occur in it, are known to us, but of the greater number of the matters that are produced during its metamorphosis, particularly of the extrac- tive matters, we are entirely ignorant. The extremely high atomic numbers of many of these sub- stances, as, for instance, of the protein-compounds, renders it very probable that each atom is decomposed into various new atoms of less atomic weight. We are, however, at present en- tirely deficient in many of the requisite data, in our knowledge regarding the connecting links, as, for instance, of the compo- sition of the extractive matters, of the difl^erent tissues, &c., without which even a superficial insight into the nature of the metamorphosis of the blood cannot possibly be obtained. With the scanty materials in our possession, we may never- theless attempt an ideal sketch of the metamorphic action that goes on in the blood, the conditions being that there is an absorption of oxygen, and that carbon is given off; it will, at any rate, afford an illustration of the facility with which such equations may be deduced, and of the slight degree of confi- dence that should be placed on their interpretation, unless they are tested by established facts. We may, for instance, suppose that 4 equiv. of the organic portion of hiematin (C^^ H^^ N3 Og), by the absorption of oxygen, will be decomposed into choleic acid, uric acid, urea, and car- bonic acid. Thus — 4At. Hsmatin . . C,76 Hsj N.j 0., T _ u ^ n 164 At. Oxygen . . . Qj-^netis.^i^O,,, BLOOD. 165 Likewise, 2 At. Choleic acid . . C„ H„ N^ 0,^ ^ 1 At. Uric acid . . . C,„ II, N, 0« I „ ^ „ 3 At. Urea . . . . Cg 11,^ Ng Og r—^m^^sa^n^iSB 76 At. Carbonic acid . . C^g O152 We can also show how cliondriu may be supposed to be formed from protein by the addition of oxygen and hydrogen : for, 4 At. Protein . . C.g, H„, N,„ O,,-, 6 At. Water . . Hg Og 1 = 5 (C3. II,s N,0,8) = 5 At. Chondrin. 16 At. Oxygen . . OjgJ We may, in a similar manner, conceive that glutiu, urea, and lactic acid are formed from protein by the absorption of oxygen, and the liberation of carbonic acid ; for 2 At. Protein .... C,„ Ilg, N,„ 0,,! _ 46 At. Oxygen .... Q^gJ ~ "" ^^"' "" Likewise, 2At.Glutin .... C.,g H.,0 N, 0,0^ 3 At. Urea Cg H,, Ng Og I ,. ^ ^ 6 At. Lactic acid . . . C^g H3, 0,, r"^^'' '^ '» "'» 12 At. Carbonic acid . . C,2 O.^^-J If we conceive that the blood-corpuscles are formed of globulin (a protein-compound), hsematin, and margarin, they may, by the absorption of oxygen and the development of carbonic acid, be decomposed into many other substances, as, for instance, into protein, cholesterin, margaric acid, urea, uric acid, and lactic acid; for, ■ ^5-.>0 ^^407 N53 Oj7g 10 At. Protein . . C400 H3.0 N50 0,,,^ 1 At. Hzematin • c,, II,, N3 Og 1 At. Margarin • C,g H„ 0,, 138 At. Oxygen . . 1 w" ATiri Q^ • o^J live Wise, 5 At. Protein . . C.JOO H,55 N« Ogo >) 2 At. Cholesterin . C74 H64 0, 2 At. Margaric acid C70 Hgg Os 10 At. Urea . . . • C,o H40 N,o 0,0 2 At. Uric acid • c,. Hs Ns 0„ 14 At. Lactic acid . Ce4 H70 O70 52 At. Carbonic acid c.,. 0,nJ i.= C.,„>H„„N,, 0., Many similar illustrations of possible metamorphic actions might be adduced; but, as they do not contribute to the ad- vancement of chemical science, we shall omit to notice them. 166 CIRCULATING FLUIDS: 2. Special chemistry of tlie blood. Proximate constituents of the blood. The blood is a fluid of a very complicated nature, and has been proved to include the following constituents in man and in certain mammalia : Protein-compounds Water, f Fibrin. Colouring matters Fats Salts ■< Albumen. L Globulin, r Hsematin. L Hsemaphsein. r Alcohol-extract, Extractive matters . . < Spirit-extract. L Water-extract. 'Cbolesterin. Serolin, Red and white solid fats, containing phosphorus. Margaric acid. l^Oleic acid. Iron (peroxide.) -- Albuminate of soda. Phosphates of hme, magnesia, and soda. Sulphate of potash. Carbonates of lime, magnesia, and soda. Chlorides of sotlium and potassium. Lactate of soda. ^Oleate and margarate of soda, r Oxygen. Gases •< Nitrogen. t Carbonic acid. Sulphur. Phosphorus. Traces of the following substances have also been detected in the blood in certain pathological states of the system : Sugar. Urea. Bihn and its acids (.'). BUiphaein. Glutin (?). Haemacyanin. Erythrogen. Hydrochlorate of ammonia. Acetate of soda. k BLOOD. 167 Beiizoate of soda. Margarin. Oleiii. Copper. Manganese. Silica. On the methods of analysing the blood. Although many of the proximate constituents of the blood may be recognized without difficulty, there are some (especially those which exist in only minute quantity) that cannot be readily detected. An exact quantitative analysis of the blood, including the determination of all the substances in the fore- going table, would, in the present state of chemistry, be almost an impossibility ; we must, therefore, content ourselves with the quantitative determination of the more important constituents, and arrange and determine the others, as, for instance, the fats, salts, extractive matters, &c. in groups. For this purpose fresh blood must be used : the clot must be allowed to sepa- rate from the serum, and the two (the clot and the serum) must then be analysed separately. The following method is given by Berzelius.^ Two known quantities of blood are taken, one of which is allowed to coagu- late spontaneously, while the other is evaporated for the pur- pose of ascertaining the quantity of water. The clot, when thoroughly separated, is removed from the first of these quan- tities, cut into pieces, and placed upon an open weighed filter, resting upon several folds of blotting paper ; it must then be covered with a similar weighed filter, over which some more blotting paper must be placed, and the whole must be compressed by a stone or other weight. The blotting paper must be changed as long as any moisture is communicated to it, and the clot must be subsequently dried in vacuo over sulphuric acid, and carefully weighed. By deducting the known weight of the filters we obtain that of the fibrin and blood-corpuscles. The dried clot must now be frequently washed with water at from 75° to 85°, until the fibrin is left colom'less. The dried blood which has been used for the purpose of as- certaining the quantity of water must be successively treated ' Thierchemie, p. 93. 168 CIRCULATING FLUIDS: with ether, alcohol, and boiling water. Tlie ultimate resi- due consists of fibrin, blood-corpuscles, and albumen; by deducting the aheady determined weight of the fibrin and blood-corpuscles, we obtain the weight of the albumen. Ether takes up the fat ; alcohol, certain extractive matters, and lac- tates ; boiling water, certain extractive matters, chloride of sodium, &c. The serum (the quantitative relation of which to the clot is known) is gently boiled, by which means the albumen is coagulated, and all moisture is removed by eva- poration. The dried residue is pulverized and treated with boiling water, which leaves albumen and fat unacted upon ; the latter of Avhich may be now taken up by ether. The water dissolves the salts, certain extractive matters, and some fat, or fatty-acid compounds. The watery solution must now be evaporated, and the residue treated with alcohol, which takes up the chlorides of sodium and potassium, the lactates, extract of flesh, and perhaps some fat, if any happens to be present. An objection may be raised against this method, that the separation of the blood-corpuscles from the serum is not suffi- ciently perfect. The complete removal of the serum is a matter of very con- siderable difficidty, in consequence of the formation of a dried surface, at those parts of the clot which are in contact with the paper, by which means a check is opposed to the egress of any moisture from the interior portions. Indeed, the moist clot can only be perfectly freed from hsematoglobulin with difficulty, and with the loss of some fibrin; if it were thoroughly dried, the difficulty would be confined to the washing out of the blood-corpuscles. But when fibrin remains for a considerable time in Avater, a small portion of it is dissolved, and a part of it is transformed into a viscid mass, consisting of very minute microscopic granides, which are not easily Avashed out. When all the blood-corpuscles are not inclosed by the coagulated fibrin, the serum assumes a reddish tint in consequence of their presence; they must then be taken into estimation with the serum. In most cases, analyses made in this manner would yield too high a number for the blood-corpuscles ; in some fcAV cases the assigned number Avould be too small. BLOOD. 169 Lecanu's method of analysing tlie blood is very similar to that of Berzelius. Denisi adopts a method of analysing this fluid which involves considerable time and manipulation; and, after all, does not give results of very great accuracy. Fresh blood is received into two vessels of known capacity, one of which is narrow and high. One portion is used for the determination of the water, the carbonate of soda, and the chlorides of sodium and potassium; the other for the estimation of the other constituents of the blood. I. The first portion is evaporated to dryness in the water- bath, pulverized in an agate mortar, again heated on the water- bath, and the quantity of evaporated water estimated. The residue is incinerated, digested in water, and filtered; the filtered solution is evaporated to dryness, and the residue is weighed, dissolved in water, and treated with nitrate of silver ; chloride of silver, and oxide of silver (?) are precipitated. This precipitate is dissolved in nitric acid, the solution is evapo- rated and crystallized; the crystals are dissolved, decomposed, and neutralized by carbonate of soda. The solution which is thus obtained (of nitrate of soda) is filtered, evaporated to dry- ness, and incinerated with animal charcoal in a platinum cru- cible. It is then digested in water, and the carbonate of soda ascertained. Upon deducting the weight of the salt from that of the whole ash of the blood, we obtain as a residue the Aveight of the chlorides of sodium and potassium. II. The other portion is allowed to stand for twenty-four hours, in order to permit of the thorough separation of the clot from the serum. The latter is removed with a pipette, and the separation is continued until incipient signs of decay present themselves. The water is removed from the serum, in vacuo, at a tempera- ture of from 120° to 140°. The clot is placed in a small bag and washed with water until all the colouring matter is removed. The residue, consisting of fibrin, is then placed in the water that has been used for the washing of the clot. The fibrin is separated by decantation, the solution of colouring matter being carefully poured off. It is then washed with fresh water. ' Recherclies experimentales sur le Sang humain, considere a I'etat sain, par S. Denis : Paris, 1830, p. 121. 170 CIRCULATING FLUIDS: In the separation of the hsematoglobulin from the fibrin, ac- cording to this method, about the seventieth part of the clot is lost in the water. The solution of the colouring matter is heated until the coagulation of the hsematoglobulin is ef- fected, which is then separated and freed from moisture by pressure. The fluids are then evaporated to dryness. We have now four subdivisions : a. The fibrin which still contains fat and cruorin.i h. Albumen with cruorin, salts, and extractive matter. c. Hsematoglobulin with fat, extractive matter, and salts of iron and the earths. d. The evaporated fluid separated from the hsematoglobulin, containing salts and osmazome. These four portions are dried, weighed, put into glass flasks, and submitted for some minutes to the action of alcohol of •800 — -820, at a temperature of 86°; they are then filtered, and the spirituous solutions united and evaporated. The re- sidue, consisting of extractive matters and salts, must be in- cinerated, by which means the quantity of extractive matter is determined. The fovir portions must now be treated with boiling water, by which cruorin and certain salts are removed. The portions a and d are now combined, and the three are treated with boiling alcohol of -800 for the purpose of ex- tracting the fat. The filtered solutions are united and evapo- rated, and the cholesterin separated by crystallization from the fats which contain phosphorus. The mixed portion of a and d contains tolerably pure albumen ; it is dried, weighed, and in- cinerated, and the ash is preserved. The second portion contains fibrin; this likewise is incine- rated, and the ash added to the former. Lastly, the hsematoglobulin is dried, weighed, and incine- rated. The collected ashes are analysed with regard to the pro- portions of peroxide of iron, phosphates of lime and mag- nesia, &c. ' Denis applies the term cruorin to a substance obtained by boiling fibrin and albumen in water. It is soluble in water, insoluble in alcohol and ether, of an agree- able taste, and precipitable by tannic acid. It appears to be produced I)y the action of the boiling water on fibrin previously affected by long contact with water. BLOOD. 171 This method is objectionable, not merely on account of tlie time and labour required for its various stages, but further, because the whole of the water cannot be estimated by the in- dicated process. Moreover, the quantity of the hrematoglobulin which is dependent upon the quantity of blood-corpuscles, will be given in excess, as it is certain that the whole of the serum cannot be separated from the clot, in the manner proposed by Denis. The determination of the fibrin may also be inac- curate in consequence of the continuous treatment of the clot with water, which has the effect of transforming a portion of it (i. e. the fibrin) into minute flocculi or granules which combine with a viscid substance. The estimation of the fat and of the extractive matters is also very inaccurate ; the quantity of fat given by Denis in his analyses being much too large, and of extractive matter, too small. Finally, no certain results with respect to the separation of the salts can be obtained by this method. Whatever may be the faults of his process, he is at least deserving of praise for having conducted no less than eighty-three analyses in this laborious manner. The method that I pursue in the analysis of the blood, if not strictly correct, at least gives results that approximate nearer to the truth than those of Denis. In explaining it, I must enter a little into detail, in order to indicate certain necessary pre- cautions, and to explain on what points it is deficient. a. I receive two, three, or at the most four ounces of blood, as it flows from the vein, in a thin glass, and stir it,i but not ■violently, till the fibrin separates. If it be stii'red too vio- lently, a portion of the fibrin becomes separated in the form of finely-divided scum, which cannot be easily collected. When the blood has completely cooled, it is weighed, together with the rod and glass, in a good balance ; it is then poured out, the glass is cleansed and dried, the rod is freed from the ad- herent fibrin, and is washed and dried : the glass and rod are then weighed, and the quantity of blood determined. b. Any fibrin that separates in flocculi from the blood must be collected, added to the former, pressed, and placed in water. If the water become strongly coloured, it must be poured off" ' [A bunch of fine twigs is generally used for this pui'pose, but the fibrin may be obtained with as much accuracy by shaking the blood in a stoppered bottle containing a few fragments of lead, to which it readily adheres.] 172 CIRCULATING FLUIDS: and renewed until the fibrin is found to be colourless, which is usually the case in from 1 8 to 24 hours. It is almost needless to mention that none of the flocculi of fibrin must be allowed to escape when we pour off the water. The decolorized fibrin is driedj cautiously broken up, pulverized in an evaporating basin, and then submitted to a temperature of 230° until it ceases to lose weight, i It is then weighed. It is again finely triturated, placed in a flask and heated, first Avith anhydrous alcohol, and then with ether, for the purpose of extracting the whole of the fat. The ether and alcohol must be evaporated in the water-bath, and the weight of the fat estimated. The quan- tity of fibrin and of fat associated with it must then be cal- culated in regard to the whole quantity of the blood. c. A quantity varying from 30 to 50 grains of defibrinated blood must be accurately weighed in a small basin, and cau- tiously heated over the flame of a spirit-lamp. This portion must then be triturated, submitted to the action of the water- bath, pulverized as completely as possible, and the heat conti- nued until it ceases to lose weight. Lastly, it must be heated in a chloride of zinc bath to 230°. The loss of weight indicates the quantity of water. d. An optional quantity (say from 400 to 600 grains) of defi- brinated blood, must be boiled over the flame of a spirit-lamp, in order to coagulate the whole of the albumen, and subsequently placed on the Avater-bath for the purpose of removing all mois- ture. As soon as the blood has become sufficiently dry to ad- mit of being partially broken up, it must be carefully triturated in a mortar, and then again placed on the water-bath. All the tough coriaceous portions, which are not easily pulverizable, must be carefully removed : by further drying they become ge- latinous, tough, and ultimately brittle. The powdered blood ought, however, if the previous steps have been properly exe- • I may observe that, in my analyses of blood, 1 always use small porcelain basins, weighing from 200 to 300 grains, and that I pulverize dried substances in the basins themselves with a small pestle. As these substances, when thoroughly dry and warm, are apt to exhibit a strong electrical repulsion of their particles, it is advisable to place the basin on a sheet of glazed paper, by which precaution any portion that may escape from it can be easily replaced. Any particles adhering to the fingers or to the pestle may be swept off with a soft feather. The most scrupulous exactness and accuracy is requisite in these investigations. BLOOD. 173 cuted^ to assume a flocculent and bright-red appearance, even before it is perfectly dried^ and sliould not exhibit any dark, glittering particles under the process of trituration. If it is black, or of a bad colour, brittle, very tough, and extremely dif- ficult to triturate, it is not fit for the purpose of analysis. e. This flocculent powder must be reduced to dryness (the trituration being at the same time kept up), and a small por- tion (8, 10, or at most 15 grains) weighed in a glass flask for further experiments. If the powder should appear to contain moisture, a small quantity (for instance about 8 grains) may be submitted to a temperature of 230° for a short time, and the whole error from this source may be thus estimated. I have found that when the powdered blood has been sub- mitted to too strong or too continuous a heat, the spirit-extract is only imperfectly taken up : hence it may be advisable not to reduce the whole of the powder to a state of absolute dryness, but rather to calculate from a small portion the quantity of retained moisture. This powder must now be treated with a little anhydi'ous alcohol. Some ether must then be poured over it, and it must be heated to the boiling point, in order to dissolve the fat as thoroughly as possible. ^ After the deposition of the powder the clear ether must be poured ofi", and the operation repeated two or three times. The ethereal solutions are then collected, the ether evaporated, and the residual fat submitted for a short time to a heat of 212°, and then weighed. f. The powdered blood, thus freed from fat, must now (after ' I use small and very thin glass flasks, containing from one and a half to two ounces (which, like all other apparatus, may be obtained from tlie establishment of Hoffmann and Eberhardt, of BerHn) : at first I pour on the pulverized blood only al)out twice its volume of alcohol ; I then heat the flask on the sand-bath, keeping it in almost continuous motion, in order that none of it may spirt over, until it boils ; I then add a considerable quantity of ether, which precipitates the salts dissolved in the alcohol, so that nothing but fat remains in solution. If too much alcohol has been added, some of the salts remain dissolved, and the apparent weight of the fat is increased. If ether alone be used for the extraction of tlie fat, the process must be repeated five or six times ; the ether should be heated in boiling water just removed from the fire. In using dilute spirit for the purpose of extraction, I heat the flask over the flame of a spirit-lamp. In both cases the flask must be kept in continual motion, in order to regulate the ebullition. 174 CIRCULATING FLUIDS: tlie ether has been removed by evaporation) be boiled in the same flask with spirit^ of -925 — -935. This must be effected by gently moving the flask over the flame of a spirit-lamp. The spirituous solution must be allowed to boil freely for some time. All the constituents of the blood are taken up except the albu- men : for the salts, extractive matters, htemaphsein, and haemato- globulin are all soluble in boiling spirit of '935. The finely- divided albumen is gradually deposited from the clear, hot, deep-red solution, which becomes turbid on cooling. On care- fully examining a thin section or stratum of the fluid, the pre- sence of albumen or of deposited hsematoglobulin in suspension, may be readily detected. In the first case, in addition to floc- culi of a larger or smaller size, there are fine, clearly-defined points to be seen. If the spirituous solution be too thick and consistent to allow of the free deposition of the suspended albu- men, the fluid must be cautiously decanted from the sediment into a large glass, and about double the quantity of spirit of •935 added. It must be heated until all the hsematoglobulin is dissolved, and then gradually cooled. When the solution is perfectly cold, we find deposited at the bottom a small quantity of separated albumen, which must be again washed with alcohol into the flask. The residue in the flask must be boiled with spirit of '935 as long as any additional colouring matter is given off: five, six, or even eight boilings are requisite. ^Tiat now remains is albumen. If the hsematin has been removed as completely as possible, the albumen, while moist, appears of a grayish-green, and when dried, of a dirty-gray colour; and leaves on incineration a bright yellow residue, containing traces of peroxide of iron. It must be washed out of the flask with a little water, with the aid of a feather ; the water must be re- moved by evaporation upon the water-bath, and the residue submitted to a temperature of 230°, and weighed. y. The spirituous solutions are collected in a glass, and usually throw down a certain quantity of hsematoglobulin, in the form of flocculi. After the decantation of the fluid, they must be dried upon the water-bath, tritiu'ated as finely as possible, rubbed with warm water to a uniform pulp, and washed with spirit of '925. They must be added to the flocculi, of which we shall speak directly. As much alcohol is now added ' I mix equal parts of alcohol of 85 or OOg with distilled water. BLOOD. 175 as is sufficient to precipitate tlie dissolved hsematoglobulin in distinct flocks. If tlie whole is now allowed to stand for 12 — 18 hours, all these flocks will be deposited at the bottom of the vessel, and there will remain above them a clear yellow fluid, which mvist be removed Avith a syphon, and the last remaining portion with a pipette. The flocks must be washed two or three times with fresh spirit of from "89 to "90, which must be re- moved by the same means. If these spirituous solutions are of a yellow or citron colour, we may assume that they contain only salts and extractive matters tinged with hoemaphsein : if they are of a reddish tint, then hsematoglobulin is also present, which must be precipitated by the addition of stronger spirit. We have now to analyse (i) the flocculi, and (ii) the spi- rituous solution. I. a. One or two ounces of alcohol of -83 or -80 (the stronger the better) are poured over the flocks ; the mixture is then well stirred, and a sufficient quantity (usually from three to eight drops) of dilute sulphuric acid is added guttatim, until a decided change of colour of the flocks is obsen^ed. The flocks are now allowed to settle, and the deep red alcoholic solution is decanted. The decolorized flocks are then treated with pure alcohol until they cease to give ofl" any more colouring matter. If, after this, the flocks have still a reddish tinge, they must be treated with a httle more acidulated alcohol. If the flocks are as free from hsematin as possible, they assume a more or less clearly defined gray colour ; when dried, they appear as a dirty- gray powder, and on incineration they leave a yellow or orange- coloured ash. b. The flocks must be washed with alcohol until they cease to exhibit an acid reaction ; they must then be washed out of the glass flask (with the aid of a feather and a little water) into a porcelain basin, be di-ied first upon the water- bath, and subsequently at a temperature of 230", and then weighed. They are estimated as globulin. c. The red alcoholic solutions are mixed and saturated with ammonia to such an extent as to emit a decided ammo- niacal odour; they are allowed to stand for some hours, in order to allow of the separation of the sulphate of ammonia ; l/C CIRCULATING FLUIDS: they are then filtered, the sulphate is washed with a little al- cohol, and the alcohol is subsequently evaporated. The re- sidue consists of haematin with haemaphsein, a trace of fat, and perhaps a little sulphate of ammonia. The latter may be taken up by Avater, at the risk, however, of losing an almost unappreciable trace of lipemaphsein, which is so far soluble in that fluid, as to communicate a yellow tint to it. d. There may be certain cases in which the perfect sepa- ration of the two colouring matters, the hsematin and hsema- phsein, would be a matter of considerable importance. In all those cases in which I have found a large proportion of haematin, as in the blood in Bright's disease, and in men- strual blood, a certain portion of haemaphsein is always asso- ciated with it. The dark coloured blood of melsena contains a peculiarly large quantity of haemaphsein. The separation of the two colouring principles is best effected by alcohol, which dis- solves the haemaphaein, but not the haematin. The alcohol should be warmed, but not allowed to boil. Upon the eva- poration of the alcohol the haemaphaein is obtained, and when thoroughly dried, may be weighed. II. a. By the evaporation of the alcoholic solutions, we ob- tain a yellow or brown residue, which has a saltish taste, and smells of extractive matters. It must be thoroughly dried, and then weighed. b. If we wish to carry the analysis further, a known weight of the residue must be incinerated. The quantity of ash from 8 to 16 grains of this residue, will be small, pro- bably from "3 to 1"0 grain. The residue likewise contains sugar, urea, and the colouring matter of the bile ; the former may sometimes be detected by the taste, and the presence of the biliphaein may be recognized by the dark colour that it imparts to the serum. In so minute a quantity of material the urea caimot be easily traced. In my analyses of the blood, I have always followed this course, and I feel convinced that if all necessary precautions are taken, the results Avill be nearer the truth than those ob- tained by any pre\dously described method. I do not, how- ever, intend to assert that my method will give exactly ac- curate results; and I shall at once proceed to point out, — BLOOD. l/T 1, Those errors against wliicli wc may guard by caution ; and 2, Those which, with all care, cannot be avoided. Water. This constituent may be determined with perfect exactness. Fibrin. If the blood be whipt with due care, the fibrin is obtained as a thick, coriaceous, fibrous mass, surrounding the twigs of the rod. It can be removed without loss, and can be easily and quickly washed. If it be stirred too rapidly, a portion of the fibrin becomes minutely subdivided, and after washing cannot be collected without some loss ; on the contrary, if it be stirred too slowly, or not long enough, the fibrin incloses many blood-corpuscles, and must either lie for some time in water, during which it is liable to a certain degree of change, or else it must be tri- turated and broken up, which indiices the formation of flocks and of a viscid matter, and occasions considerable loss. With a little experience and practice, the fibrin may be de- termined with great exactness. It is necessary to submit the dried fibrin to a temperature of 230°. Fat. The fat contained in the fibrin may be estimated with great accuracy. It is only necessary to boil the pulverized fibrin with ether, or (which is better) with a mixture of ether and anhydrous alcohol, for four, five, or six times. The deter- mination of the quantity of fat in the dried pulverized blood is much less certain and accurate. In an analysis in which I separated the hsemaphrein, I treated a large quantity of pul- verized blood, six successive times with boiling ether, in a retort ; yet I still found a considerable quantity of fat in the hsematin. This may be due, partly to the compounds of mar- garic and oleic acids becoming decomposed by the sulphuric acid in the alcohol dming the boiling of the powdered blood which had been treated with ether ; and partly, I believe, to a little free fat which had not been taken up by the ether. The fat appears to be extracted most perfectly when the powdered blood has been first loosened, as it were, with an- hydrous alcohol. A quantity of ether, just sufficient to pre- cipitate the salts dissolved by the alcohol, must then be added, 12 178 CIRCULATING FLUIDS: We may safely calculate tliat the whole of the free fat has heen taken up, after six or seven extractions with ether. If, after- wards, the hsematin should still be found to contain fat, some of the fatty acids must have been present, and acted upon by the acidified alcohol. Albtmien. Errors may arise in the determination of the albumen. These may be due, in the first place, to want of care in drying and pulverizing the blood. If the powdered blood has been allowed to dry into a cracked, brittle, tough, hard mass, which can only be repulverized with difiiculty, and usually with considerable loss, then, only a portion of the hsematoglobulin is taken up by the spirit, some of it now ap- pearing of a yelloAV or gi ay-green colour, while another part of it occurs in the form of coarse black fragments, resisting the action of alcohol. This albumen has a somewhat red tint, and upon incineration leaves an ash, which is tolerably rich in iron. Another source of error may lie in the spirit, which may be either too strong or too weak. I have always found a mixture of equal parts of alcohol of 85 — 90^, and of water, succeed best. I have occasionally found that with all precautions, and after boiling the residue with spirit until no more hsemato- globulin was taken up, the albumen has stiU retained its red tint, and left an ash abounding in iron. I have never been able to ascertain the reason why diluted boiling alcohol should occa- sionally fail in the perfect extraction of the hrematoglobulin. If, after continuous boiling with dilute alcohol, the albumen still retains a red tint, I heat it with alcohol of -80 — -82, in the same flask, and during ebullition I gradually add one, two, or even four drops of dilute sulphuric acid. The alcohol, at first colourless, now assumes a red tint, and the albumen, which is deposited upon standing, is either free from colour, or becomes so after being once more boiled in strong alcohol. It must then be boiled several times in alcohol of 0*925, which takes up the sulphate of globulin, and leaves the albumen.^ ' As sulphate of albumen is insoluble in alcohol, we need not be apprehensive of losing any albumen by this extraction. I have convinced myself, by a special inves- tigation, that spirit of '925 takes up nothing but sulphate of globulin from the pul- verized residue of the blood. The fluid, while hot, is perfectly clear, but becomes rather turbid on cooling, in consequence of the separation of fat. BLOOD. 179 The alcoholic solution of the sulphate of hsematin Avhich (unless the alcohol -were too dilute) contains no globulin, may be poured into a flask, and united Avith the fluid, which is subsequently obtained on the separation of the haematin from the globulin, {i, c.) The sulphate of globulin separates pretty completely in the form of flocks from its alcoholic solution, on cooling. The supernatant spirit, which frequently has a slightly acid reaction, must be evaporated, till only a little is left ; and we must then try whether upon the addition of strong alcohol, any globulin will still be precipitated. The whole of the sulphate of globulin must be added to that which is subsequently obtained from the hiematoglobulin. If, in accordance with the methods of Berzelius and Denis, the clot is washed for the purpose of obtaining the fibrin, the nuclei and capsules of the blood-corpuscles are entangled in, and increase the apparent quantity of the fibrin ; if however the fibrin is removed by whipping, according to my method, then the nuclei and capsules remain in the albumen, and in- crease its estimated quantity. I am not acquainted with any researches tending to show the degree in which the proportions of albumen and fibrin are modified by the adoption of one or other of these methods. Maitland,^ however, observes that the quantity of fibrin ob- tained by whipping is less than that obtained by washing the clot. Midler,^ on the contrary, thinks that the weight of the nuclei must be extremely small, and that the results obtained by the two methods are very nearly the same. My o^vn opinion is, that the fibrin cannot be determined Avith accuracy from the washed clot. Globuliti. The globulin can be calculated with considerable accuracy if the albumen has been perfectly freed from the hsematoglobulin. I have never yet succeeded in entirely remoAdng the hsematin from the globulin. It is known that even nearly colourless globulin leaves, on incineration, an ash which is pretty rich in peroxide of iron. Whether globulin generally contains peroxide of ii'on or not, I cannot positively ' An Experimental Essay on the Physiology of the Blood, 1838. * Physiologic des Menscheu, vol. 1, p. 119. 180 CIRCULATING FLUIDS : state. The globulin usually occurs in analyses of tlie blood as a sulphate^ and as sucli I have abvays estimated it. It is of a grajdsh-white coloiir, forms a brownish solution in water, and on incineration leaves an ash, more or less abundant in iron. If after the separation of hsematin (in the manner already described), and after being washed in alcohol, the globulin retains a red tint, it must be again treated with a lukcAvarm mixtiu'e of sulphuric acid and alcoliol, as before, which dis- solves the hsematin that had remained attached to the glo- bulin. It must then be repeatedly washed with alcohol, until it no longer exhibits any acid reaction. Hamatin. From the remarks which have been made re- specting the albumen and the globulin, the reader may con- clude that the hsematin cannot always be determined with exactness ; I conceive, however, that with all due care, the error in the determination of the hsematin should be very trifling in 100 parts. It by no means necessarily follows that hsematoglobulin should under all circumstances contain a con- stant proportion of hsematin. Moreover, if the fat has not been previously entirely removed, a certain quantity may be associated with the ha^matin. If the lijemaphfein is separated from the hsematin by means of warm alcohol, the fat dis- solves simultaneously with the former of these colouring mat- ters, and remains closely connected with it. If the alcohol used for the separation of the hsematin from the globulin is not sufficiently strong ; and if, after the saturation of the sul- phuric acid with ammonia, a sufficient time is not allowed for the sulphate of ammonia to separate, a portion of this salt will pass through the filter, and become mixed with the hiEmatin upon the evaporation of the alcohol. If this is the case, the salt may be easily recognized in the hsematin by its crystalline form ; and it must be extracted with water. It is always advisable to use strong alcohol, and to allow the satu- rated solution to stand for some hours before it is filtered. Hamaphain. The determination of this constituent is somewhat uncertain and difficult, on account of the minute proportion in which it exists. It is occasionally found to BLOOD. 181 constitute only 0-1^ of the weight of the dried blood, A portion of this colouring matter is taken up with the ex- tractive matters from which we cannot separate it ; another portion may be lost if the alcohol used for the separation of the hjematin from the globulin is not of sufficient strength. In this case, on saturating with ammonia, a sulphate of ammonia is precipitated, and its removal is associated Avith a further loss of hsemaphsein. The hoemaphasin always retains a little fat. Salts and extractive matters. These substances, with due caution and experience, may be determined with considerable accuracy. They must be separated from the haematoglobulin by the addition of dilute spirit, and to ensure a tolerably perfect separation, the whole should be allowed to stand from eighteen to twenty-four hours. I have already mentioned the com'se that must be adopted in case any of the htematoglo- bulin should be retained in the alcoholic solution. If the ex- tractive matters and salts are evaporated on the water-ljath to a slight residue, and then treated with anhydi'ous alcohol, the alcohol-extract Avill be dissolved and may be estimated. I do not know how to separate hsemaphcein from the extractive matters. In order to determine the salts, the extractive matters must be incinerated. By treating the (incinerated) residue with hot alcohol of "85, we take up the chloride of sodium. The residue must be dissolved in a little water, and rendered neutral by the addition of acetic acid. The acetates of potash and soda may now be taken up by alcohol. These salts correspond with the lactates. i There still remain the ' [The existence of lactic acid and the lactates in the animal fluids is denied in toto by the Giessen school. Enderlin's conclusions regarding the recently incinerated ash of blood may be summed up in the following terms : 1. The ash does not effervesce on the adtUtion of an acid. 2. Hot water poured on the ash becomes alkaline ; it holds in solution alkaline phosphates and sidpliates, chloride of sodium, and sometimes chloride of potassium, but no other salts. a. On the addition of a neutral solution of nitrate of silver to this fluid, there is a yellow precipitate, which is partly soluble in nitric acid ; a portion, however, con- sisting of chloride of silver, remaining undissolved. The addition of nitric acid causes no effervescence. On neutralizing the acid filtrate with ammonia, a yellow precipitate of tribasic phosphate of silver (3Ag 0, PO^) is thrown down. b. On treating the aqueous solution of the ash with a solution of chloride of cal- 182 CIRCULATING FLUIDS : phosphates and sulphates of lime^ magnesia, potash, and soda. If they are dissoh^ed in a httle dilute nitric acid, the addition of ammonia induces the precipitation of the earthy phosphates, while the other salts remain in solution. There are some substances occurring only in very minute quan- tities, or in certain diseased states, which cannot be always easily detected. 1. Urea. This substance has never yet been observed in any great quantity in the blood. I have detected a minute quantity of urea in the blood of a healthy calf. I allowed the blood (about fifteen or sixteen pounds) to run into a vessel filled with alcohol, and assiduously stirred the mixture. The alcohol was removed by pressure, evaporated, and the residue extracted with anhydrous alcohol. After filtra- tion, and a second evaporation, the residue was again dissolved in a little anhydrous alcohol, and the bases of the lactates and fatty acids precipitated with sulphuric acid. The filtered liquid was digested with carbonate of baryta, evaporated, dissolved in water, the fats and fatty acids removed by filtration, the aqueous solution concentrated, and nitric acid added. The greater part of the fluid was removed by being placed in vacuo over strong sulphuric acid; alcohol was poured over the residue, and the cium, there is a copious gelatinous precipitate of phosphate of lime (3CaO, PO^), which dissolves in nitric acid without eflfervescence. On treating this acid solution with nitrate of silver, and neutralizing with ammonia, the tribasic phosphate of silver is precipitated as before. The addition of the chloride of calcium neutralizes the previously alkaline fluid. From 1, we see that the alkaline reaction is not due to the presence of alkaline carbonates ; and 2 shows it is not dependent on the presence of free potash or soda, for otherwise the fluid would not be neutralized by the chloride of calcium. Hence the albumen in the blood cannot exist as a soda-compound (albuminate of soda) ; neither can there be alkaline lactates, acetates, nor fatty-acid salts in that fluid ; and on the above grounds, Enderlin conceives that we are justified in assuming that the alkaline reaction of the ash is dependent on the presence of tribasic phosphate of soda (3NaO, PO,) ; and as this is the only salt that remains tribasic at a red heat, he concludes that the alkalinity of the blood, as well as of the ash, is dependent on it. Enderlin is tlie oidy chemist who excludes carbonates from the ash of the blood and other animal fluids. The manner in which he accounts for the occurrence of these salts in the analyses of other chemists is very plausible. On exposing 3NaO, PO5 to the atmosphere, it becomes converted into 2NaO, HO, PO5 andNaO, CO2. (Liebig and Wohler's Annalen der Chemie und Pharmacie; March 1844.)] BLOOD. 183 solution submitted to spontaneous evaporation. The microscope then revealed the presence of nitrate of urea^ wliicli was recog- nized by its peculiar crystalline form. [Marchand got only slight microscopic indications of urea from twenty pounds of the serum of the blood of a healthy cow; and as the urine of that animal contains a larger amount of urea (4^ according to Sprengel) than that of man^ the blood must likewise contain a larger proportion of this ingredient. He calculates (assuming that there are twenty pounds of blood in a man^s body, and that one ounce and a half of urea is eli- minated in twenty-four hours) that the blood contains only the 15,360th part of its weight of urea, a quantity that could hardly be determined analytically, if it were increased thirty-fold.'] After the extirpation of the kidneys, and in Bright^s disease, it has been found in so large a proportion that its detection is accomphshed with comparative ease. My method, in looking for urea, is to treat a certain quantity of the blood Avith alcohol for the purpose of throwing down the protein-compounds ; then to filter ; and, subsequently, to wash the residue upon the filter with alcohol. The alcoholic solution (including the washings of the filter) must be evaporated to a small residue, and treated with anhydrous alcohol. The solution is decanted from the spirit-extract, which remains undissolved, is evaporated, and again treated Avith anhydrous alcohol. This process must, if necessary, be repeated until the residue is freely soluble in this menstruum. The alcohol must then be evaporated, and the residue dis- solved in water, which usually becomes slightly turbid in con- sequence of the separation of traces of fat. This fat is not easily separated by filtration ; if, however, this process is deter- mined upon, a considerable quantity of water is added ; it is heated, and allowed to stand for some time. The watery solu- tion will then pass through the filter tolerably clear, but slowly. It must be evaporated to a small residue, thoroughly cooled, and nitric acid then added. If the quantity of m-ea is not too minute, there are formed almost instantaneously an immense number of glittering crystalline scales. If the quantity of urea ' [That there is a peculiar difficulty in the precise determination of this constituent is shown l)y an experiment in which Marchand mixed one grain of m'ea with 200 of serum. He could only recover -2 of a grain.] 184 CIRCULATING FLUIDS: is very miniite, the crystallized nitrate of urea may not be per- ceptible for several liom*s, and even then probabh^ not without the aid of the microscope. In order to avoid any errors that might arise through the crystalline form of other salts^ I first made myself thoroughly acquainted with the appearance pre- sented under the microscope by alcohol-extract of urine (con- taining urea) when treated with nitric acid ; then with the appearance presented by alcohol-extract of blood to which a little urine had been added^ on the addition of nitric acid ; then with that of alcohol -extract of blood devoid of urea ; and^ lastly, with blood which contains urea in the natural proportions. In this manner I found that the salt which most commonly occurs in the alcohol-extract of blood, the lactate of soda, may be readily distinguished under the microscope from the nitrate of urea, and that very minute quantities of urea may be detected with certainty. Small quantities of urea may be recognized, by the peculiar and characteristic form of the nitrate, in fluids containing those extractive matters and salts of ui*ine or of blood that are soluble in anhydrous alcohol. The forms which are principally and most frequently observed are depicted in fig. 3 : a represents the characteristic crystalline form of nitrate of urea ; b, c, d, e, groups that are formed in a somewhat dilute solution of urea ; f, groups that are formed in a very dilute solution, chiefly at the edge of the fluid. Fig. 4 exhibits the crystalline form which is produced by the addition of nitric acid to the alcohol-extract of blood, containing no urea. These crj^stals are not perceptible until the fluid is evaporated nearly to dryness. Fig. 5 shows the form of the nitrate of lu'ca in blood containing a conside- rable quantity of urea. I have several times observed these appearances in Bright's disease. With a little practice the commencement of the crystallization of the nitrate may be perceived ; it begins by exhibiting an appearance of numerous fine parallel lines or streaks. Oxahc acid may likewise be used in microscopic researches regarding the presence of urea in the blood. I have always, however, preferred the use of nitric acid, because, in the first place, it is not itself capable of crystallization as oxalic acid is ; and, secondly, because the nitrates of potash and soda are much more soluble than the corresponding oxalates. Fig. shows BLOOD. 185 the cn-stalline form of the oxalate of urea when alcohol-extract of urine, not very rich in urea, is treated with oxalic acid. In a, we see the characteristic crystalline form of the oxalate of urea ; b, represents various groups of it. If the alcohol-extract of blood containing no lu-ea be similarly treated, the crystals of fig. 7 are produced. Lastly, fig. 8 shows the crystals of oxalic acid itself, which ai-e very similar to those of pure crystallized urea. On treating the extractive matter of blood containing no urea with nitric acid, I have occasionally perceived crystals which, at first sight, appeared extremely similar to those of nitrate of urea, but which were in reahty composed'-of nitrate of soda. These crystals are exhibited in fig. 9. They possess a very remarkable degree of thickness,^ which I have endea- voured to represent in the plate. They may be distinguished from the similar form of nitrate of m'ea, by the circumstance that the former are not at all soluble in anhydrous alcohol, Avhile the latter are readily dissolved in it. If nitrate of urea be pre- sent, it will recrystalHze from its tJcoholic solution in groups similar to those in fig. 10. 2. Sugar. This substance, which I once discovered in the blood of a calf, is very seldom to be found in healthy blood, although in certain pathological states, especially in diabetes meUitus, it has frequently been detected. If the quantity be very small, its presence is not always easily recognized. It is found mixed with the extractive matters, if the blood is analysed according to my directions, and if it exists in any quantit}^, may be recognized by the taste. If only a very little sugar be present, it is ad\isable to precipitate the protein-compounds from a large quantity of blood, with spirit. The fluid must then be filtered and evaporated to a small residue, Avhich must be treated with anhydrous alcohol. The sugar, if present, must be taken up by the alcohol. If, after due evaporation, the residue have a sweetish taste, a portion of the sugar may be obtained tolerably pure, since its quantity cannot be very incon- siderable. AVith this %iew we dissolve it in a httle water, add alcohol of -833, and allow it to stand for some time ; under ' This is easily seen by slightly vai'ying the ftciis. 186 CIRCULATING FLUIDS : favorable circumstances^ a portion of the sugar will crystal- lize. In consequence of its intimate mixture Avith a large quantity of extractive matter, an exact quantitative analysis of tlie sugar is extremely difficult. The best method is that of fermentation, and estimating the quantity of carbonic acid that is formed. If the quantity of sugar be very minute, it cannot be recognized by the tongue, in consequence of the sweetness being disguised by the taste of the salts and extractive matter ; it may, however, in this case, be detected by sulphuric acid, although this test is fallacious in the hands of unpractised analysts. The method to be pursued in this case is the same as that previously indicated ; the spirituous solution must be evaporated, treated with anhydrous alcohol, and the fluid de- canted. The precipitate which contains extractive matter, chloride of sodium, lactate of soda, and sugar, must be dissolved in water ; and if (as is frequently the case) any hsematoglobulin remains undissolved, the fluid must be filtered. The filtered fluid must be evaporated to dr}Tiess in a porcelain basin, on the water-bath, and one or two drops of dilute sulphuric acid (one part of acid to six of water) must be dropped upon the dried residue. On again submitting it to the heat of the water-bath, it is observed that those points which have been moistened by the acid at first assume a blue or violet tint, become gradually darker, and ultimately coal-black. When the quantity of sugar is very small, the colour is only sufficiently marked at the margin of the drop, or at points where the layer of extractive matter happens to be particularly thick. Unfortunately for the suc- cess of this test, a dark spot, varying from a deep brown to a dark dirty-violet tinge, but never positively black, is produced in the same manner in the spirit-extract of blood, which con- tains no sugar; so that, without a well-practised eye, it is difficult to decide upon the absence or presence of sugar by this test. After the addition of one grain of diabetic sugar in solution, to 500 grains of blood, (which contained no sugar,) no decided sweetness could be observed in the spirit-extract. The sulphuric acid test indicated the presence of sugar by the for- mation of a coal-black spot ; on the addition of the acid to a portion of the extract of the same blood in which there was no sugar, a dirty violet spot was produced. In examining the blood of diabetic patients I once found so large a proportion of BLOOD. 187 sugar that it was readily detected by the taste ; on another occasion^ however, it was only rendered manifest on the addi- tion of sulphuric acid. But of all the tests for sugar in the blood, Trommer's is certainly the best. The protein-compounds are first precipitated with anhydrous alcohol, and diy carbonate of potash is then added to the filtered spirituous solution, which must be well shaken. On the addition of a little solution of sulphate of copper, and the application of heat, Ave observe, if sugar be present, a yellow or yellowish brown tint developed, produced by the reduction of the copper to a state of suboxide. 3. Bile. In healthy blood we find neither bilin nor bili- phsein. In icterus we meet with biliphaein in the serum, Avhich is more or less deeply coloured in proportion to the quantity of this pigment contained in it. It may be of a deep orange, or almost red colour, so as to lead to the suspicion of the presence of hsematin in a state of solution. I found the serum nearly blood-red in a case of icterus ; but on shaking it against the sides of the vessel, the thin adhering layer appeared of a beautiful saffron colour. A similar colour was induced by the addition of water to the serum. If only so small a quantity of biliphaiin be present as to colour the serum slightly, it may be recognized by the addition of nitric acid, which produces a variety of tints, more or less green in their character. The albumen is at the same time precipitated in white flocks, upon which a slight tinge of green may be distinctly perceived. ^ In the deep red serum already alluded to, the addition of nitric acid produced an intensely clear grass-green colour, which, at some points, passed into a blue, and, in the course of twenty-four hoiu's, into a yellow tint. The quantity of biliphsein varies directly with the intensity of the colour of the serum, and with the time required for the dis- appearance of the green tint, produced by the addition of nitric acid. Neither in the blood already alluded to, nor in another specimen which contained less biliphsein, could I discover a trace of bilin. The alcohol-extract of the blood had a saltish, but ' [In consequence of the facility with which coagulated albumen assumes a green tint under these conditions, we are often enabled to detect biliijha;in (that would be otherwise unappreciable) in non-albuminous fluids, by the addition of a little albumen.] 188 CIRCULATING FLUIDS : not a bitter taste. I am not aware that bilin or bilifellinic acid^ has ever been observed in the blood, and I hardly believe that they will be found, owing either to their not being taken up by the blood at all, or else to their speedy elimination by the ui'ine. A large quantity of bilin would have a very dangerous effect upon the blood, since (as we have already shown) it dis- solves the blood-corpuscles. I treated 500 grains of blood with half a grain of inspissated ox-bile, and then precipitated the protein-compounds with spirit, evaporated the fluid, and treated the residue with anhydrous alcohol. It is clear that the bile must be contained in this residue. After the evaporation of the alcohol, there remained a rather dark-coloured extract, having a bitter bile-like taste, and which, when dissolved in water, and nitric acid was added, manifested a slight green tinge. If, there- fore, the bilin should constitute one-thousandth part of the blood, it would be easily detectible. If the analysis of the fats and of the extractive matters is to be thoroughly carried out, (as in many cases it certainly ought to be,) much larger quantities of blood must be taken than I have made use of. The various fats, however, as well as the different extractive matters, are at present too little known to enable us to attempt exact, or even approximating quantitative analyses. 4. Fats. Boudet^ has analysed the fats which are taken up by alcohol from dried blood, after all substances that could be extracted by water have been removed. The alcoholic solution deposits serolin on cooling, which must be separated, and the alcohol evaporated. There remains as a residue a mixture of several fats, which were separated by Boudet in the following manner. Cold alcohol of 'SSS leaves undissolved a crystalline fat which contains phosphorus, and is apparently similar to the brain-fat, denominated cerebrot by Couerbe. Cholesterin is deposited by the spontaneous evaporation of the cold alcoholic solution ; and on finther evaporation, (after the removal of the cholesterin,) there is left a mixtm"e of oleic and margaric acids, ' [Eriderlin states that he has detected minute quantities of choleate of soda (pure bile, according to Demar9ay's theory) on three occasions, in the blood of calves and oxen. (Annales der Chemie und Pharmacie, April 1844.)] * Annal. de Chim. et de Phys., vol. 52, p. 337. BLOOD. 189 as well as some oleate and margarate of potash. In addition to these fats, there are certain colonred phosphorized and nitroge- nous fats, similar probably to those which have been described by Couerbe, as ceplialot and eleencephol. Lecanu found, in the fiit of the serum, only cholesterin, serolin, margaric and oleic acids ; he could detect no phosphorized fat. Berzehus^ describes the fat of the fibrin, which may be taken up either by alcohol or ether, as solid and crystalline; when melted, of a yellow or light brown colour, readily soluble in cold alcohol, to which it imparts an acid reaction, indicating the presence of one or more of the fatty acids. Upon burning it, no acid ash is left. Denis,2 on the other hand, obtains from fibrin, as well as from albumen and hsematoglobulin, a red phosphorized fat, which has an alkaline reaction. By digestion in caustic potash, a pai-t is dissolved, while an insoluble portion remains, in the form of a white, saponified powder, readily soluble in ether, from which it may be again obtained, by spontaneous evapo- ration, in the form of delicate crystals, which burn like fat. The portion of saponified fat which is dissolved in the potash must be precipitated by hydrochloric acid, and cannot be melted in the acid fluid, even on raising the temperature to a boiling heat. After having been removed by filtration, it is found to be soluble in alcohol and ether, and we may obtain it, after evaporating the fluid in which it is dissolved, as a fat, which becomes fluid at a temperatm-e of 97° — 104°, but is solid at an ordinary temperature. It has an acid reaction, and swells up, but is only very partially soluble in boiling water, from Avhich, on evaporation, we obtain it (the dissolved portion) as a sort of film or coating. According to Berzelius, it is similar to the acid salts of stearic and oleic acids described by Chevreul; it differs from them, however, by its greater solubility in ether and cold alcohol. 5. Extractive matters. These substances have been less care- fully analysed than the fats, and the proportions in which they occur, are so small, that even in the analysis of a large quantity ' Thierchemie, p. 88. ^ Recherches Experimentales, &c. p. 101. lOO CIRCULATING FLUIDS: of blood, their exact determination is no easy matter. All that is known upon the subject is already given in the Intro- duction. [A simple method of determining some of the most important constituents of the blood has been recently given by Figuier. It is based on the fact, made known many years ago by Berzelius, that after the addition of a solution of a neutral salt to defibrinated blood, the globules do not (as before) pass through filtering paper. On the addition of two parts of a solution of sul- phate of soda of spec. grav. 1"130 to one of blood, Figuier found that the whole of the corpuscles remained on the surface of the filter. The following are the steps of his analysis. The fibrin is removed by whipping, dried, and weighed; the weight of the corpuscles is ascertained by the method indicated ; and that of the albumen by coagulating, by means of heat, the filtered solution. The proportion of water is determined by evapo- rating a small known weight of the blood.] Afialysis of coagulated blood. It sometimes happens that we receive blood for analysis that has already coagulated. The process to be adopted in such cases, although not in reality more difficult, involves a greater amount of chemical manipulation than when the fibrin is sepa- rated by whipping ; and it appears to give less exact results. The directions that I shall now give for the analysis of co- agulated blood were published in a paper of mine some time ago;^ I have, however, only once adopted this method, as I always prefer analysing the blood directly it is taken from the body. The whole of the blood must first be weighed as accurately as possible, the clot must then be removed, and if sufficiently consistent, dried between folds of blotting paper, and then weighed. A portion of the clot (from 40 to 80 grains) is cut off", and its weight accurately taken ; it is then thoroughly dried, and the loss of weight, which indicates the quantity of water, ascertained : the dried residue must be reduced to a spongy, bright-red fine powder, and treated with ether in order to remove the fat: it must subsequently be treated with boiling ' Brande's Arcliiv, vol. 28. BLOOD. 191 alcoliol of -925 until the spirit ceases to take up any addi- tional colouring matter, and the powder which remains has a dirty-gray or gray-green colour. This must be thoroughly dried, and estimated as fihrin and albumen. The reddened alcoholic solution, a, is set aside for further operation. Another portion of the clot must be weighed and placed in a porcelain mortar, which should be provided with a pestle of such a size as exactly to fill it. Moreover, the edge of the mortar should be about one third of an inch above the head of the pestle. By this arrangement none of the clot can be lost. It must be reduced to a fine pulp, which must be treated with water until the flocculi of fibrin become perfectly white : these must be carefully collected and dried. By the subtraction of the weight of the fibrin from that of the former residue, Ave obtain the weight of the albumen. Before analysing the serum, it must be w^ell shaken in order to render its constitution uniform; a portion must then be weighed, coagulated at a boiling heat, thoroughly dried, again weighed, and the proportion of Avater thus estimated. The dried residue must be finely pulverized, the fat removed by ether, and it must be then boiled with alcohol of -925 until everything which is soluble in that fluid has been taken up. The residue consists of albumen, which must be dried and Aveighed. The alcoholic solution must be added to the solution A, and these mixed fluids analysed for the globulin, haematin, hsemaphsein, extractive matters and salts, in exactly the same manner as described in page 175. ON THE HEALTHY BLOOD IN RELATION TO PHYSIOLOGY. [From my owti analyses.) It is almost unnecessary to observe that the blood of one and the same indiAddual may vary in its constitution at dif- ferent times, and under different circumstances. We shall proceed to investigate the causes upon Avhich these variations depend. Amongst the most obAious causes we may place the proper supply, or the absence of sufiicient nutrition. The blood will clearly abound in water, in proportion to the quantity of fluid with which it is supplied; it Avill abound in 192 CIRCULATING FLUIDS: albuminous constituents, in fats, and salts, in proportion to the riclniess of tlie nutriment that has been taken, and of the chyle that has been evolved from that nutriment. In order to coun- teract the evils that might arise from an excess of water in the blood, (which, if allowed to remain unchecked, would induce too rapid a solution of the blood-corpuscles,) the kidneys, skin, and lungs exert an active agency ; while, on the contrary, if there be a deficiency in the proportion of the water, caused either by too great exhalation, dependent upon excessive fatigue, or by a direct accumulation of the salts (which might impede the solution of the corpuscles) it is immediately indicated by an urgent desire for drink. When substances, injurious to life, are taken into the sto- mach, only small quantities enter the blood, the great pro- portion being usually carried off by the intestinal canal, and by the organs of excretion and secretion. If the organism be unequal to the task of rejecting the injurious agent, the equi- librium of the system is destroyed, and death ensues. Another cause of the vai'jdng nature of the blood, inter- esting equally to the physiologist and the physician, may be referred to the modifications that it undergoes in the nutrition of the organism, and to the changes undergone by the cor- puscles, in connexion with the processes of secretion and excretion. On the distinctive characters of arterial and venous blood. The distinctive colours of arterial and venous blood are too well known to require any observation.' ' [From Scherer's experiments it appears that, when fresh red ox-bloorl is deprived of its fibrin and diluted with twice or thrice its volume of water, it assumes a dark venous tint, which is not affected by the passage of a current of oxygen through it. On the addition, however, of a little milk, oil, finely-powdered chalk or gypsum, the original bright red colour is evolved. These experiments are sufficient to prove that the bright red colour is dependent on other causes than oxidation, and that the dark venous tint does not arise from carbonic acid or carbon ; in fact Scherer conceives that they prove that the former is dependent on the presence of white particles of chyle suspended in the fluid, an opinion confirmed by the microscope. It was observed by Hewson that, when the colour of the blood is bright red, the corpuscles are always biconcave ; they reflect a large amount of hght, and in this respect act as the chalk, milk, &c. in Scherer's experiments. When, on the other hand, the blood is of a dark colour, the corpuscles are biconvex, and the capsule is so thin as to admit Ox BLOOD. 193 Arterial blood, on being whipt, allows the fibrin to separate in short conglobate masses, more tenacious and compact than the fibrin of venous blood. The odoiu' of arterial blood is considered to be stronger than that of venous. The temperature is also usually stated to be different, Jurine being the only experimentalist who assigns an equal temperature (i. e. 102°-2) to both forms of blood. Ac- cording to Scudamore the temperature of arterial blood in man is l°-8, according to Kramer 2°-7, higher than venous blood. Dr. D&vj found the diff'erence in animals amount to 3°-6. The observations of Colemann, Cooper, and Martini are directly opposed to the above statement. (Lecanu, Etudes chimiques sur le Sang.) The relative capacity for heat of arterial and venous blood is, according to Davy, as 839 to 852. There is considerable diff'erence of opinion among physiolo- gists with respect to the specific gravity of arterial and venous blood : Hammerschmidt, Davy, Scudamore, and Letellier assert that the density of arterial is lower than that of venous blood ; the former being represented by 1039-8 — 1042-9, the latter by 1053—1056. the easy passage of the whole light through it ; moreover, on account of its attenu- ation, it hursts, and allows of the escape of its contents, as may be observed on the addition of water to red blood. If the blood remain in contact with water till a dark tint becomes apparent, and a saturated solution of a neutral salt be then added, the corpuscles again become biconcave, in consequence oftheir being partially emptied by the endosmosis called into play by the different fluids within and without the capsule; and the capsules themselves, and the original bright red colour reappear. A current of carbonic acid gas passed through fresh red blood renders the corpuscles biconvex, and makes the blood assume a dark venous hue. Mulder explains the difference between the colour of arterial and venous blood in the following manner : Two oxides of protein are formed in the act of respiration ; they have a strong plastic tendency, and solidify round each corpuscle, making the capsule thicker and better qualified to reflect light. Each corpuscle of the arterial- ised blood is then in reality invested with a complete envelope of bufiy coat, which gradually contracts, and speedily forms the cupped or biconcave surfaces, which, as we have already shown, are favorable to the reflection of hght. On reaching the capillaries, the coating of the oxides of protein is removed, and the corpuscles, losing their opaque investment and their cupped form, can no longer reflect light, and the blood assumes a venous tint. (Mulder's Versuch einer allgemeinen physiologischen Chemie, pp. 344-59 ; or Dr. G. Bird's account of Mulder's Researches, in the Medical Gazette, December 1844.) 13 194 CIRCULATING FLUIDS: Boissier and Hamburger, on the contrary, found arterial denser than venous blood. The observations of Bellinger!' respecting the electric rela- tions of arterial and venous blood are very singular. In birds, horses, and occasionally in sheep and calves, both forms of blood are in the same electric state. In other animals the arterial blood is positively electric in relation to the venous. The reverse has never been observed. Observations have also been made regarding the comparative tendency to putrefaction of arterial and venous blood. Kriraer and Kanig assert that arterial blood is the most prone to decay; Thackrah, on the contrary, makes a similar statement respecting venous blood. In order to obtain any correct information with regard to the differences that undoubtedly exist in the composition of arterial and venous blood, it is necessary to have recourse to accurate chemical analyses. I have devoted much attention to this point, and fully concur with Schultz, Dumas and Prevost, and others, in the belief that the two forms of blood present marked difiPer- ences of constitution. I made use of the blood of horses in these experiments, and was kindly assisted by Professor Gurlt. The carotids, from which we obtained the arterial blood, were exposed, and opened in such a manner as to ensure the absence of any venous blood : the venous blood was obtained from the jugulars. The analyses were made according to my ordinary method (vide supra), and gave the following results.^ 1000 parts of blood contained : Analysis 1. Analysis 2. Arterial blood Venous blood. Water 760-084 757-351 Solid residue 239-952 242-649 Fibrin 11-200 11-350 Fat 1-856 2-290 Albumen 78-880 85-875 Globuliu 136-148 128-698 Haematin 4-872 5-176 Extractive matter and salts 6-960 9-160 100 parts of tlie blood- corpuscles 1 100 parts of tbe blood-corpuscles contained 3"4 of liamatin. 1 contained 3-9 of hajmatin. Quoted by Lecanu. Etudes Chimiques sur le Sang humain, p. 75. It must be observed that no sound horses were used for these experiments, but BLOOD. 195 The horse, which was suffcriuj^ from malleus hiiraidus, had taken its ordinary food up to the time of its death. Analysis 3. Analysis 4. Arterial blood. Venous blood. Water 789-390 78G-506 Solid residue 210-610 213-494 Fibrin 6-050 5-080 Fat 1-320 1-456 Albumen 113-100 113-350 GlobnUn 76-400 78-040 Haematin 3-640 3-952 Extractive matter and salts 10-000 10-816 100 parts of blood-corpuscles i 10-1 pai-ti 5 of ])lood- corpuscles contained 4-5 of haematin. 1 contained 4-8 of hsematin. This was a meagre horse, killed in consequence of debility and old age. From these analyses Ave are led to the conclusion that arterial blood contains less solid residue generally than venous blood : it contains less fat, less albumen, less luematin, less extractive mat- ters and salts than venous blood. The blood-corpuscles of arterial blood contain less colouring matter than those of venous blood. There does not appear to be any fixed relation between the fibrin and globulin (or, which is nearly the same thing, the mass of the blood-corpuscles,) in the contrasted analyses ; for in Nos. 1 and 2 the fibrin in the venous exceeds that iu the arterial blood, wdiile in Nos. 3 and 4 we observe exactly the re- verse. The same fluctuation is observable with respect to the globules, or the mass of the blood-corpuscles. In an analysis of the blood of a healthy ox, made with the same object, I found the quantity of fibrin to be larger in the arterial than in the venous blood. In the former case it amounted to 4-90, and in the latter to only 4-82 in 1000 parts. I shall now give the results obtained by other chemists upon this subject : I must, however, observe that their methods of analysis differ considerably from mine, and that I consider some of their results questionable. only those intended for anatomical purposes. Some were too old and weak to be of any use ; others were suffering from incurable disorders. Although it may be fairly questioned whether the composition of the blood in these animals is normal, the correctness of the comparative results must be unaffected as long as the lungs and other secreting and excreting organs remain healthy, provided there is no reason for supposing that the general metamorphosis of the blood is morbidly affected. 196 CIRCULATING FLUIDS : Denis analysed the blood of the hound, parts : He found in 1000 Arterial blood. Venous blood. Water .... 830-0 830-0 Fibrin .... 2-5 2-4 Albumen 570 58-6 Haematoglobulin 99-0 97-0 Extractive matter and salts 11-0 12-0 In this instance both kinds of blood contain an equal pro- portion of solid residue : the former contains, as I have already observed in two out of three anal3'ses, a larger quantity of fibrin. Denis found, as I have also done, that the quantity of albumen, and of extractive matters and salts, is less in arterial than in venous blood. Heringi has analysed both kinds of blood in the bullock, the sheep, and the horse. In the blood of the bullock he found in 1000 parts : Arterial blood. 798-9 7-6 26-1 164-7 Water .... Fil)rin .... Albumen Hffimatoglobulin Extractive matter and salts 2-7 Venous blood. 794-9 6-6 25-8 170-4 2-3 In the blood of the sheep he found in 1000 parts : Water .... Fibrin .... Albumen Haematoglobulin Extractive matter and salts Arterial blood. 850-2 61 33-6 106-1 4-0 Venous blood. 841-2 5-3 26-4 124-4 2-7 In the blood of the horse he found in 1000 parts : Water .... Fibrin .... Albumen Ilaematoglobulin Extractive matter and salts Arterial blood. 839-5 4-6 22-0 130-0 3-0 Venous blood. 831-6 6-9 26-7 131-1 3-7 These analyses correspond very well with each other, and corroborate our remark that arterial leaves a smaller amount of ' Physiologic mit steter Beriicksichtigungder Pathologic fiir Thieriirzte. Stutgart, 1832, p. 118. BLOOD. 197 solid residue than venous blood. In the bullock and sheep the fibrin in arterial exceeds that in venous blood ; in the horse the reverse is observed. The same observation holds good Avitli regard to the albumen, and in this respect (at least in the case of bidlocks' and sheep^s blood) Hering's results differ from those of Denis and myself. Hering invariably found the quantity of blood-corpuscles to be greater in venous than in arterial blood ; the proportion of extractive matters and salts are, however, extremely fluctuating. Lecanu' has likewise analysed the blood of the horse, and found in 1000 parts : Blood of aorta. Blood of vena cava descendens. Water .... 783-83 795-679 Blood-corpuscles . . 122-68 106-759 Albumen with its salts, ex--i .„ ^„ „. , .„ , , V 93-49 9/ -562 tractive matter and salts J Blood of carotid. Blood of jugular vein. Water .... 785-5 804-55 Blood-corpuscles . . 125-6 111-03 Albumen with its salts, ex- n „„ „ r> i i c I 88-9 84-45 tractive matter and salts J These analyses diff'er from my own, and from those of Denis and Hering, in assigning to arterial a larger solid residue than to venous blood. The quantity of blood-corpuscles is also greater in arterial than in venous blood, and Lecanu found the same to be the case with regard to the quantity of fibrin. The quantity of albumen fluctuated. Schultz^ observed that the venous blood of hungry and starv^- ing horses contained a larger amount of solid residue than the arterial, in the proportion of 186 to 155 in 1000 parts of blood : in a well-fed horse the reverse was the case, the solid residue of the arterial being to that of the venous blood, in the proportion of 229 to 195. The quantities of fibrin were very fluctuating : on one occasion the fibrin of the arterial was to the fibrin of the venous blood in the proportion of 5-3 to 8-1 ; on another occasion as 9-2 to 9*0. The haeraatoglobidin (which he considers identical with the colouring matter of the blood) was found to vaiy directly with the darkness of the blood^s colour, ' Etudes chimiques sur le Sang humain. Paris, 1837, p. 83. ' System der Cirkulation, p. 138. 198 CIRCULATING FLUIDS: and consequently to be more abundant in venous than in arterial blood. 1 The reverse was the case with respect to the albumen. Autenrieth, and Prevost and Dumas,^ found a greater proportion of solid constituents in arterial than in venous blood : Lassaigne, like myself, found just the reverse : whilst Letellier asserts that there is no fixed rule on the subject. Miiller'* and Berth old* observe that in the goat there is a larger proportion of fibrin in arterial than in venous blood : the latter chemist extends the statement to the blood of the cat and the sheep. The observations of Sigwart^ and Lassaigne^ are opposed to these statements. Prevost and Dumas obtained from arterial a larger propor- tion of blood-corpuscles than from venous blood, and in this respect they confirm the observations of Lecanu and Denis. My own analyses, and those of Letellier, tend, however, to show that the proportion is a fluctuating one. Hence we are led to the conclusion that there are certain dif- ferences in the composition of arterial and venous blood, which, however, are not constant, but vary according to circumstances. The most important of these circumstances are the general health of the individual, and the mode of nourishment, whether dependent upon or independent of the health. Let us now consider what must be the qualities of arterial and venous blood when all the functions of the organism are properly discharged, when the nutrition exactly corresponds with our actual Avants, and when the blood undergoes the various changes that we have described in a former page. Under these circumstances we arrive a jiriori at the con- clusion that the final result of the changes in the blood during ' In order to avoid the error that miglit arise in the detemiination of the hsemato- glohuhn from the retention of serum in the clot, Sehultz proceeded in the following manner : He dried the clot, and suhtracted from its residue the amount of solid matter left hy a quantity of serum corresponding to the expelled moisture. The diiference he regarded as hamatoglobulin. We must not, however, forget that the ha^mato- glohulin does not exist in a dry state in the blood ; and, further, that there are no grounds for assuming that the fluid in which it is held in solution is serum. * Annales de Cliimie et de Phys., vol. 13. ^ Physiologic des Menschen, vol. 1, p. 119. * Burdach's Physiologic, p. 281. •'' Reil's Archiv, vol. 12, p. .'). •"* Journal de Chimie Med. vol. 1, j). 31. BLOOD. 199 the act of circulation must necessarily be this : there must be a substitution of fresh and proper nutriment to supply the place of those constituents of the blood which are being perpe- tually consumed ; for it is obvious that if in each circulation the consumption of albumen or hsematoglobulin exceeded the supply by the merest trace, after a certain period the blood would acquire an abnormal constitution. We know that al- bumen, fibrin, and salts are consumed in the nutrition of the peripheral system ; if therefore the blood receives no fresh supply of these substances, before it arrives in the larger venous trunks, it is clear that the venous blood must be poorer in these substances than the arterial. The blood also conveys away from the peripheral system various products formed by the consumption of the tissues ; for instance, certain salts, extractive matters, &c., some of which are eliminated by the kidneys, in a state of great dilution, while others are removed by the skin. If the quantity removed exceed the supply, the venous blood will be poorer in ex- tractive matters and salts than the arterial ; it will be richer in these substances if the reverse be the case. The venous blood will contain more or less water than the arterial, according as the elimination of water by the kidneys, liver, skin, and lungs, exceeds or is less than the quantity supplied by the fluid of nutrition. The blood-corpuscles, and the germs from which they are developed, are hkewise supplied to the blood by the nutrient fluids. They are farther developed, and ultimately dissolved during the course of the circulation, and their development and solution is especially facilitated at those points where the action of oxygen on the blood is the most powerful. It is obvious that the blood, immediately after having re- ceived the chyle, must contain more blood-corpuscles than before; it depends however upon several circumstances whe- ther venous generally contains more or less corpuscles than arterial blood. The plasma receives a supply of fibrin from the solution of the blood-corpuscles ; if the supply exceeds the consumption of this constituent in the peripheral system, the venous blood may become richer in fibrin than the arterial. If any albumen should be produced by the solution of the 200 CIRCULATING FLUIDS: blood-corpuscles, it may be regarded as a substitute for the portion of that constituent which has been taken up from the blood for the nourishment of the tissues. From these observations we are led to conclude that there is no necessary variation in the composition of venous and arterial blood. The organism, when free from disturbing in- fluences, possesses in itself various means of regulating the due admixture of its diff'erent juices, and more especially of that most important vital fluid, the blood. Amongst these means we may place the influence of the nervous system, its power of increasing or lessening the action of the secreting and excreting organs, and of inducing in them either co-operating or vicarious action. The differences in the constitution of arterial and venous blood cannot, however, by any possibility be very great. In my analyses they usually fluctuate between fractions of a hundredth part ; and they appear to be less between analyses 3 and 4, than between analyses 1 and 2, since the former (anal. 3 and 4) were made on the blood of an old decrepid, half-starved horse, in which the change and waste of tissue, and the consequent metamorphosis of the blood, would be very slight. That the diff'erence must be small is obvious, when we consider that the whole course of the circulation may be accomplished in 25-30 seconds ; that the plasma just con- veyed to the tissues must everywhere propel the nutrient mat- ter conveyed there by the preceding blood-wave, and that the tissues, everywhere saturated with nutrient plasma, only take up a supply proportioned to their consumption. The process of nutrition in the peripheral system is continuous and is sup- ported by the liquid plasma with which all the tissues are sur- charged; hence these tissues become the temporary recipients of far more nutrient matter than they can possibly consume, even as the rivulet contains infinitely more water than is ne- cessary for the refreshment of the soil on its banks. In both cases we found that the venou,s blood contained a larger proportion of solid constituents than the arterial ; hence we infer that more water was removed by means of the kidneys, liver, and skin, than had been supplied to the blood by the nutrient fluids. The quantity of fibrin in the venous blood in analysis 2 is BLOOD. 201 greater tlian in the arterial blood, although, from our know- ledge of the fact that fibrin is employed in the process of nu- trition, we should have expected an opposite result. Hence we are led to attribute the excess of fibrin to the consumption of a large proportion of blood-corpuscles, a view which is con- firmed by the circumstance that the venous blood in this in- stance is poorer in blood-corpuscles than the arterial. The proportions are reversed in analysis 4, but whether from opposite causes or not, I cannot decide. It is singular that in both instances the quantity of albumen is greater in the venous than in the arterial blood, since there can be no doubt that this constituent is consumed in the nutrition of the tissues, and that a portion of the changed plasma enters the lymphatics. I do not see how this increase can be accounted for, unless we assume, as I have previously done, that a portion of the globulin of the blood-corpuscles is converted into albu- men during their metamorphosis. In the present state of our knowledge regarding the meta- morphosis of the blood, it is as difficult as it is hazardous to attempt to explain the various causes upon which the differ- ences between venous and arterial blood are founded. There are, as I shall proceed to show, decided diff'erences between the blood of the renal arteries and veins, and between the blood of the hepatic vein and of the vena portse ; and yet, as has been already shown, the diff"erences between the blood of the aorta and of the vena cava are very immaterial and trifling. To produce this ultimate similarity, other changes (not yet heeded by the physiologist) must have largely contributed. Properties of the blood of the vena portce ; — its comparison ivith arterial blood. The blood of the vena portae in horses (the only animals in which I have examined it) is darker than ordinary venous blood ; the diff'erence of the tint is however so slight, as to be observable only upon actual comparison. It coagulates more slowly than ordinary arterial or venous blood ; the clot is less firm, more of a gelatinous appearance, and falls to pieces if an attempt be made to lift it. I analysed the blood of the vena portse of tlie two horses already alluded to. If arterial, ordi- nary venous, and vena portse blood are deprived of their fibrin 202 CIRCULATING FLUIDS: by whipping, and are then allowed to stand, the blood-cor- puscles subside in nearly equal times ; but while they occupy little more than one half of the volume of arterial or ordinary venous blood, in portal blood they form nearly three fourths of the whole volume. In portal blood, after the lapse of several hours, a delicate glittering film was formed upon the surface of the serum, which when seen under the microscope was found to contain fat-glo- bules ; I could not however discover any lymph-granules either in the serum or amongst the blood-corpuscles. The arterial and ordinary venous blood, on the contrary, exhibited lymph- granules, but no fat-globules. The blood of the vena portse not only contains less fibrin than arterial or ordinary venous blood, but the qualities of that constituent are also different ; it is not so consistent as ordinaiy fibrin, and does not separate into the firm, globular, little masses that are obtained by whipping arterial blood. Our knowledge of the properties of this blood has been ma- terially increased by the researches of Schultz.^ The follow- ing are his principal conclusions : It is darker than ordinary venous blood, but the diflerence of tint is sometimes so slight, as to be hardly perceptible. It is darkest in fasting horses, but after a full meal, it becomes brighter. These differences are more striking than those between arterial and venous blood. Common salt, nitre, atmospheric air, and even oxygen, when shaken with the dark blood of the vena portae, have scarcely any effect upon the colour, whereas venous blood would be changed to a brighter red by these reagents. If the blood of the vena portse be not extremely dark, a slight change is perceptible. If a portion of this black blood be treated with a quantity of common salt or nitre sufficient to prevent it from coagu- lating, coagulation may still be induced (although not until after several hours, and then very slightly) by the addition of water, while venous blood similarly treated coagulates in the course of five or ten minutes. If the blood is very dark, it sometimes does not coagulate at all; if it is not very dark, it occasionally coagulates in the same time as ordinary venous blood ; the clot, however, is very ' System (Icr Civkulation, p. 140. BLOOD. 203 soft, and either entirely, or at least its lower surface, dissolves in the course of from twelve to twenty-four hours. Schultz further observes that after the blood has been whipt, the cor- puscles sink very quickly ; he ascribes this peculiarity to an excess of colouring matter attached to the capsules of the blood-corpuscles . As the blood of the vena portse that I analysed was taken from the same two horses from which I obtained the arterial and venous blood, a fair comparison may be instituted with respect to their differences of constitution. 1000 parts contained : Analysis 1. Analysis 5. Arterial blood Blood of vena portae. Water .... 760-084 724-972 Solid residue 239-952 257-028 Fibrin .... 11-200 8-370 Fat .... 1-856 3-186 Albumen 78-880 92-400 Globulin .... 136-148 152-592 Ha^matin 4-827 6-600 Extractive matter and salts 6-960 11-880 100 parts of blood-corpuscles 100 parts of blood-corpuscles contained 3-4 of haematin. contained 4-1 of haematin. Analysis 3. Analysis 6. Arterial blood. Blood of vena portae. Water .... 789-390 815-000 Solid residue 210-610 185-000 Fibrin .... 6-050 3-285 Fat .... 1-320 1-845 Albumeu 113-100 92-250 Globulin 76-400 72-690 Hsematin 3-640 3-900 Extractive matter and salts 10-000 11-632 100 parts of blood-corpuscles ■ 100 parts of blood-corpuscles contained 4- " of hffimatin. 1 contained 5*3 of h^matin. It is only in four respects that the results obtained by a comparison of these two analyses of the blood of the vena portae with arterial blood at all coincide : the former contains less fibrin, more fat, more extractive matter and salts than the latter, and lastly, the proportion of colouring matter to globulin is greater in the former. In order to give a better idea of the relative proportions of the colouring matter, I shall quote another analysis of the 204 CIRCULATING FLUIDS : blood of tlie vena portse, which was made for the purpose of comparison with the blood of the hepatic vein. In this analysis the colouring matter is separated into hse- matin and hsemaphsein. I obtained from 1000 parts : Analysis 7. Water 801-500 Solid residue .... 198-500 Fibrin 6-200 Fat 2-700 Albumen 90-000 Globulin 75-600 Haematin 3-400 Haemaphsein .... 1-800 Extractive matter, with some h^mapliaein, "I i < . < nn r A"*' 400 and with salts . . . . > This blood was veiy rich in colouring matter, there being no less a proportion of it than 6-8 in 100 parts of blood-cor- puscles, of which 4-5 were hsematin and the remaining 2"3 haemaphsein. In addition to this, the extractive matters re- tained a considerable quantity of liBemaphsein. The circumstance that the blood of the vena portse in analy- sis 6 contains less solid residue, and a smaller proportion both of albumen and blood-corpuscles than arterial blood, while the reverse is observed in analysis 5, need not excite much"surprise when we remember that in analyses 3, 4, and 6 the blood was taken from an old, decrepid, starved animal. Schultzi has made some very important observations on the relative constitution of the blood of the vena portae, as contrasted with arterial and ordinary venous blood. Solid constituents. The blood taken from the vena portae of fasting horses gave, as a mean of three analyses, 16-90|J of solid constituents, while arterial and venous blood gave IS'SG^ and 18*62 respectively : ' Schultz's analyses of the portal blood would, in my opinion, have yielded more important results, both as regards the absolute and the comparative composition of the fluid, if he had determined all the constituents from the same identical blood. He appears to have used the blood of different animals for the determination of the different constituents. The absolute composition of the blood is assuredly different in different animals, but there are also relative differences depending on age, nutri- tion, and other circumstances. BLOOD. 20.) it contained therefore (in tins instance) a greater proportion of solid constituents than arterial ; a less proportion than venous blood. This proportion, 16-90|^, is however less than is usually met with in arterial or venous blood. The blood of the vena portie of a horse fed with oats gave 20-35 of solid constituents, while the arterial and venous blood of the same animal gave 22*91fj and 19*55 respectively. Here the solid constituents of the blood of the vena portse bear an exactly opposite proportion to those of arterial and venous blood, for in this case they exceed those of arterial, and are less than those of venous blood. The amount of the per-centage of the sohd residue, although still deficient, approximates very nearly to the ordinary average, ]\Iy observations from analysis 5 are at variance with these remarks. Fibrin. As an average of thi'ee analyses, '325 of fibrin was obtained from the blood of the vena portse, while the proportions obtained from arterial and venous blood were 1*04^ and l*09g respectively. Hence it may be concluded that this blood is poorer in fibrin than either arterial or venous blood — a point which is con- firmed by my own observations. Albumen with salts, and blood-corpuscles.^ The following results were obtained from his analyses : 1. 2. 1. 2. 1. 2. Blood of vena portae. Arterial blood. Venous blood. Albumen . . 8-16g 9-67^ 9-862 ii-ilg 7-962 ii.25g Blood-corpuscles . 8-74^ 10-53g 4-65g 10-21g 9-2ia 6-95g The analyses 1 were made with the blood of fasting horses ; the analyses 2 with the blood of horses after a recent meal of oats. Hence it follows that the blood of the vena portse contains more blood-corpuscles and less albumen than arterial or venous blood. My own analyses do not exactly coincide with these remarks. Fat. The solid residue of the blood of the vena portse gave (as the mean of four analyses) 1-66^ of fat, Avhile the corresponding ' Scliultz's method of analysis is described hi note 1, p. 198. 206 CIRCULATING FLUIDS: proportions of fat in arterial and venous blood amounted to only •92^ and -SSg respectively. Hence it appears (and in this re- spect my own observations confirm those of Schultz) that this blood contains a larger proportion of fat than either arterial or venous blood. The albumen and the clot contain individually a larger quantity of fat in this than in ordinary blood. Schultz has observed a very striking difference between the quantity of fat contained in the fibrin of this and of arterial blood : the former yielded 10-7^, while the latter gave only 2'34§ of fat, which in the first case was brown and discoloured, in the latter was Avhite and crystalline. It follows from these remarks that there is no constancy in the deviations of the blood of the vena portai from arterial or venous blood. The reason of the mutability of the composition of this blood is easily accounted for, if we consider the relation that the ramifications of the vena portse bear to the digestive organs, and the absorbent power of the veins, as shown by the experiments of Magendie,i Tiedemann, and Gmelin.^ The rapid removal of water from the stomach can, moreover, only be explained by the agency of the vena portae. Hence it is evident, both from my own analyses and those of Schultz, that the blood which is conveyed to the hver by the vena portse diff'ers in well-fed and in fasting animals. When fluids, containing a smaller proportion of solid residue than ordinary blood, are absorbed by well-fed animals, we may naturally infer that the blood of the vena portae will be more deficient in solid constituents than either arterial or venous blood. This view is confirmed by the observations of Schultz, excepting in the case of the horse that had been fed with oats shortly before its death, when a greater solid residue was left by this blood than by either the arterial or venous : in this in- stance, however, the residue was below the ordinary average of either venous or arterial blood. In fasting horses the residue is considerably below the average of ordinary blood. The remarkably small quantity of fibrin that is invariably found in the blood of the vena portae, as well as the large pro- portion of fat that is associated Avith the fibrin, is a point of con- siderable interest ; as also the large proportion of blood-corpuscles ' Precis elementaire de Physiologic, par Magendie. Bruxelles, 1838, ji. 328. ' Miiller's Physiologie des Mensclien, vol. 1, p. 241. BLOOD. 207 observed by Scbultz, and which occurred, in rather a striking degree, in my analysis 5. It is of importance to trace the origin and development of these peculiarities, as we may thus be led to take clearer views of the functions of the liver and the preparation of the bile. Schultz' attributes the source of all these peculiarities to the intestinal canal, to the lymphatic glands, and to the spleen. The organization and vitality of the chyle, prepared in the intestinal canal, require (according to Schultz,) the co-operation of the plasma, which (being thus partially consumed) leaves a large proportion of blood- corpuscles, the majority of which ap- pear to have been deprived of their nuclei by absorption, and to have been converted into empty capsules impregnated with colouring matter. To this is attributable the preponderance of the clot. The large quantity of fat is ascribed by Schultz to absorption of the chyle, and he considers that its dark colour is in some way connected with the metamorphosis of the co- louring matter of the blood-corpuscles. My own views with respect to the causes of the peculiar constitution of this species of blood differ, in a few immaterial points, from the ingenious explanation of Schultz. There are two reasons for the very small quantity of fibrin in this blood. In the fii'st place it may take up a quantity of fluid containing little or no fibrin, by which means the relative proportion of filn-in in a given quantity of blood must of course be diminished; and, secondly, it may be explained by the torpid motion in this part of the circulatory apparatus, and the de- ficiency of atmospheric oxygen : this latter reason may also account for some of its other peculiarities. In consequence of the deficiency of oxygen, the metam.orphosis of the blood- corpuscles must be imperfect, deficient, and retarded, and the solution of the developed corpuscles will not be duly effected. To this cause we must ascribe not merely the diminished quan- tity of fibrin, but the retarded solution, and the accumulation of the corpuscles, especially of such as are fully developed and abound in hsemaphsein, the consequent accumulation of that colouring substance in the plasma, and the necessarily dark tint of the serum, which possesses no means of throwing off that constituent. ' Op. cit. p. 322. 208 CIRCULATING FLUIDS : The large proportion of fat is chiefly attributable to the fluids that are produced during the act of digestion^ and which are conveyed into the portal vein. In examining this blood under the microscope, I have seen that it is rich in fat globules. The deep yellow (or sometimes even brown) tinge of the fat is produced by hsemaphsein, which is very soluble in fat and cannot easily be extracted from it. The fatty acids do not seem to undergo any change in the liver, for we find them, as well as the cholesterin of the blood, again in the bile. The cholesterin is particularly abundant, and is probably one of the products of the function of the liver. Properties of the blood of the hepatic vein ; — its comparison ivith the blood of the vena portee. I am not aware of any analyses of the blood of the hepatic vein having been made previously to my own. Very important conclusions might doubtless be drawn re- specting the constitution of the bile, by contrasting the analyses of the blood of the vena portse with that of the hepatic vein, if it were not that we had to take into consideration with the former the blood of the hepatic artery with which it mixes in the capillary system of the Kver. As the contents of the hepatic vein are discharged into the vena cava inferior, immediately as it leaves the organ, it is no easy matter to obtain any considerable quantity of the blood in a pure and unmixed state. Professor Gurlt has kindly assisted me in collecting specimens of this blood from horses. The blood of the hepatic vein difi'ers, in several respects, from any of the forms of blood that have been hitherto considered. It appears to be darker than the blood of the vena portse, (when contrasted with it,) but becomes of a somewhat brighter colour by continued stnring. The separation of the fibrin is more difficult and tedious than from the blood of the vena portse, and this constituent, when deposited on the rod, is possessed of very little consistence, is soft, gelatinous, and difficult to wash, a portion of it falling to pieces and being distributed through the water. The blood, after the removal of the fibrin by whipping, continues to manifest a tendency to gelatinize; the blood-corpuscles de- BLOOD. 209 posit themselves and form a dark coagulated clotted mass under the siu'facc of the serum, from which no additional fi])rin can be obtained by further stirring; and upon allowing it to rest, the same phenomena are again exhibited. On placing a little of the blood, immediately after stirring, on a glass slip, the blood-corpuscles may be seen to collect into minute islets or spots ; at least I observed this to occur in three specimens of this sort of blood that I analysed at different times. In one instance I found that the lilood had actually coagu- lated, but slowly, after the removal of fibrin by whipping, and upon renewed stu-riug I obtained a small quantity of stringy or coriaceous fibrin. Microscopic analysis. On examining a specimen of this blood, not diluted with the ordinary solution of salt, the swollen corpuscles were observed moving about; some were distinct, some partially united with others; these gradually attached themselves to one another and formed irregular groups of various sizes, in which the outHnes of the individual corpuscles could no longer be recognized. It appeared as if the corpuscles exuded a plastic matter, which might possibly be the cause of their adhering to each other. On diluting the blood with a solution of hydrochlorate of ammonia, I once observed that the medium-sized corpuscles appeared studded with minute pearly beads, (vide supra, page 105.) The following observation which I made upon two occasions interested me extremely, I saw a great excess of small blood-corpuscles, about one fourth or one sixth of the ordinary size, whose true nature could only be recognized by their well-marked yellow colour, and by their passing from a spherical into a flattened form, when rotation was excited. The motions of these minute blood-corpuscles resembled those of Brown^s molecules, and were much more active than those of the ordinary corpuscles in common blood. The analysis of the blood of the hepatic vein gave in 1000 parts — 14 210 CIRCULATING FLUIDS Water Solid residue Fibriu Fat Albumen Globulin H;ematin Extractive matters and sal Analysis 6. Blood of vena portse. 815-000 185-000 3-285 1-845 92-250 72-690 3-900 11-623 100 parts of blood-corpuscles contained 5-3 of haematin. Analysis 8. Blood of hepatic vein. 814-000 180-000 2-650 1-408 103-283 57-134 3-000 12-312 100 parts of blood-corpuscles contained 5-2 of h.xmatin. The blood was taken from the starved horse^ who siipphed the matter for analyses 3 and 4. Analysis 9. Analysis 10. Blood of vena portse. Blood of hepatic vein. Water 738-000 725-000 Solid residue 262-000 275-000 Fibrin 3-500 2-500 Fat 1-968 1-560 Albumen 114-636 130-000 Globulin . 116-358 112-000 HiTniatin 4-920 4-420 Hffimapbffiin 1-467 1-040 Extractive m atters and salts 10-236 17-160 1 00 parts of blood-corpuscles 100 parts of blood-corpuscles contained 5-4 of colouring contained 4-8 of colouring matter of which 4-2 were matter of which 3-9 were hffimatin and 1-2 hsema- hsemati n and 0-9 hama- phsein. phaein. From these anabases we deduce the following conclusions. The blood of the hepatic vein is richer in solid constituents than that of the vena portse, and consequently than either ar- terial or ordinary venous blood ; it contains less fibrin, fat, globulin, and colouring matter, than the blood of the vena portse; the ratio of the colouring matter to the globulin is smaller, and the quantity of albumen larger in the former than in the latter form of blood. In consequence of the admixture of the blood of the hepatic artery with that of the vena portse in the capillary system sur- rounding the biliary ducts, and of the catalytic influence of the cells of the liver in the formation and secretion of bile, it is impossible for us to ascertain the relative parts which these two distinct forms of blood play in the production of this important BLOOD, 211 secretion, or to state with certainty which constituents are drawn from the contents of tlie Iiepatic artery and which from those of the vena porta?, or how the withdrawal of them is effected. These analyses are nevertheless of great importance, since they show that the blood-corpuscles are actively engaged in the secretion of the bile, a view which corresponds with and tends to explain other phenomena connected with this secretion. They show that the blood of the hepatic vein contains more albumen and less globulin, or (which is much the same thing) blood- corpuscles, than that of the vena portse. These differences favour the hypothesis that the corpuscles (or, at least, theu^ principal constituent, the globulin,) have a greater share in the formation of the bile in the peripheral system of the liver than the albumen, the principal constituent of the plasma. Another corroborative circumstance is the small amount of colouring matter in the blood of the hepatic vein, from which we infer that some of it has been consumed in the formation of the bile, a view which accounts, with more probability, for the origin of its colour than the supposition that it is produced from a portion of the plasma.^ If the liver were supplied with blood from the vena port^e alone, there could be hardly a doubt entertained with regard to the correctness of my hypothesis ; the influence of the blood of the hepatic artery must not, however, be overlooked. If, for instance, the blood of the hepatic artery contained a much larger proportion of albumen and a smaller quantity of blood- corpuscles than the blood of the vena portae, the mixture of these would produce a fluid similar in constitution to the blood of the hepatic vein. But, upon comparing the blood of the vena portae with that of the hepatic artery, no such proportions, as those we have assumed, are observable. It is true that a mixture of the two bloods in a badly fed animal would contain more albumen, but, at the same time, more blood-corpuscles than the blood of the vena portae (see Analyses 3 and 6) ; and in the reverse case (see Analyses 1 and 5) the mixture would ' [This view is corroborated by Mulder, who observes that if the blood-coqouscles undergo a metaniorphic change prior to their development into living tissue, the products of the decomposition of the hasmatin may be probably traced in the Mli- fuhin of the bile. (Versuch einer allgeraeinen physiologischen Cheniie, p. 358.)] 212 CIRCULATING FLUIDS: contain fewer corpuscles, but, at tlie same time, less albumen, than the blood of the vena portse. It is impossible to account for so large an amount of albumen in the blood of the hepatic vein, if we consider the quantity of bile which is secreted by the healthy liver, and attribute its formation to the elements of the plasma alone ; whereas, if we consider the bile to be formed at the expense of the blood- corpuscles, the peculiarities in the blood of the hepatic vein are at once accounted for. In addition to the separation of the bile, the liver effects a further change in the blood by draAving from that fluid the sources of its own nutrition. These two processes merge into one, which may be regarded as the product of the development of the hepatic cells. The formation and secretion of such a complicated fluid as the bile, by the action of the hepatic cells on the plasma, may be dependent on various causes. The entire structure of an organ must necessarily correspond with its func- tions, and with every variety of internal organization there will be a corresponding variation in the secretion. The action of the hepatic cells on the plasma is different from that of the renal or other glandular cells, in consequence of the difference of their chemical action on the blood. The nerves also seem to influence the secretions. Further, since the plasma has been modified in its progress through the liver by the solution of a large number of blood- corpuscles, a corresponding new product must be evolved from it by the hepatic cells. I have previously stated that the de- velopment, and especially the raltimate solution of the blood- corpuscles may occur in all parts of the peripheral system, if a sufficient supply of oxygen be present. I have shown that a large quantity of fully developed corpuscles accumulates in the blood of the vena portje, in consequence of its torpid motion and the want of a due supply of oxygen ; if this blood mixes in the capillaries with the well-oxygenised blood of the hepatic artery, it is not difficult to conceive that a proportionably larger quantity of blood-corpuscles is thus dissolved in a given time than at many other parts of tlie peripheral system, that the plasma may thus become changed, and that the product of the general action of the hepatic cells may be different. It is well known that the liver is one of the most active BLOOD. 213 organs of the animal economy. Even in the embryo, the de- velopment of its cells is wonderfully abundant, as has been shown by lleichert. In the adult the activity of the liver is exhibited by the increased secretion of the bile during di- gestion. The activity of an organ is represented by the in- tegral of the activity of its cells ; and the increased activity of the cells is intimately connected with the facilit}^ of evolution and revolution. If, then, in consequence of the activity of the liver as a secreting organ, a large number of cells are con- sumed, it follows that a proportionably large number must be reproduced; and we can thus explain the apparently incon- sistent phenomena of the blood of the hepatic vein containing less fibrin than that of the vena porta, by the supposition that, although a large quantity of blood-corpuscles is consumed by the liver, the fibrin of the plasma supplies the materials for the formation of c}i:oblasts for new cells. All the other differences that are observable between the composition of the blood of the hepatic vein and of the vena portse may be accounted for by paying a little attention to the nature of the bile. The bile contains a smaller proportion of solid constituents than the blood ; hence it is obvious that the blood, previously to the separation of the bile [i. e. the blood of the vena porta?) must contain a smaller proportion of solid constituents than after this change has been effected {i. e. the blood of the hepatic vein.) The blood of the vena portae contains more colouring matter, both hsematin and htemaphsein, than that of the hepatic vein. It is impossible to decide with certainty upon the manner in which these colouring substances are consumed in the liver, as we are still deficient in correct ultimate analyses of biliphsein and hsemaphsein; we may, however, safely conclude that the biliphsein is produced by the metamorphosis of the colouring matter of the blood. Properties of the blood of the renal veins ; — its comparison with the blood of the aorta. The blood of the renal veins was drawn from a horse simul- taneously with the aortic blood ; it was found, however, upon opening the body of the horse, bled to death, that the renal 214 CIRCULATING FLUIDS: veins contained so small a quantity of blood that Professor Gmit was unable to collect from them more than about 50 grains. The blood obtained in this manner was visibly darker than the aortic blood. I stirred it for a considerable time with a rod, but could obtain no fibrin ; on leaving it to stand, it became gelatinous, and resembled the blood of the hepatic vein after similar treatment. Microscopic analysis. Upon comparing the two sorts of blood under the microscope, the only perceptible differences were the following : In the unmixed blood of the renal veins the corpuscles united themselves into islets and amorphous groups, in which the individual globules could not be traced. Upon mixing some of this blood with a solution of salt, a larger quantity of small and middle-sized corpuscles were ob- served than in the aortic blood when similarly treated. The proportion, however, of the small corpuscles to the large ones was not so striking as in the blood of the hepatic vein. (Vide supra, p. 209.) In consequence of the small quantity of material, I resolved to determine only the most important of the constituents. I made an accurate estimate of the proportions of water and albumen, but was prevented by illness from ascertaining the quantities of globulin and hsematin. 1000 parts of blood contained : Analysis 11. Analysis 12. Aortic blood. Blood of renal vein. Water .... 790-000 778-000 Solid residue . . . 210-000 222-000 Fibrin .... 8-200 .' Albumen . . . 90-300 99-230 From these analyses it appears that the blood of the renal veins is more abundant in solid constituents and in albumen than the aortic bloody but that it contains less fibrin and fewer blood-corpuscles. The two latter inferences, respecting the quantity of fibrin and of blood-corpuscles in the blood of the renal vein, cannot be drawn from the analyses in the same certain manner as in the comparative analyses of the blood of the hepatic vein and of the vena portic. BLOOD. 216 Although I cannot believe that this blood is entirely devoid of separable fibrin, it eertainly contains less fibrin than arterial blood. In fact it is more than probable that the quantity of fibrin which is formed during the coiu'se of the blood through the renal capillary s} stem, where oxygen is taken up and not again supplied, does not exceed the quantity consumed. Although no determination of the haematin and globulin was instituted, we may infer, analogically, from our former analyses, and from the necessary reciprocating proportions of the two principal constituents of the blood, that less hsematoglobulin exists in the blood of the renal veins than in that of the aorta. If the albu- men in each be estimated in regard to equal quantities of the solid residue, the albumen in the aortic blood will be found to be to that in the blood of the renal vein in the ratio of 425 to 446. The quantities of hsematoglobulin will tlierefore be in an opposite ratio. These results throw considerable light upon the changes which the blood undergoes in the kidneys. It loses a certain quantity of water, which is accounted for by the urine. Hence this blood contains less water than the aortic blood. Urea appears to be formed from the corpuscles, under the cooperating influence of the plasma and oxygen of the blood, rather than from the albumen, which preponderates in the blood of the renal veins the same as in the hepatic vein. It cannot be 2)ositively asserted that the observations which were made regarding the trifling amount of fibrin in the blood of the he- patic vein, as compared with that in the blood of the vena portse, here hold good, but there are many reasons in favour of such an analogous \'iew. It is highly probable that the activity of the excreting powers of the kidney is due to the activity of the organ itself, as has been abeady observed with regard to the liver, and that this activity corresponds with the energetic evolution and revolution of renal cells. That the kidneys do not separate bile, but urea, uric acid, and salts, is due partly to the chemical constitution of the renal cells and to the pecuharly directed cooperation of the nerves of these organs, and partly, perhaps, to the composition of the l)lood itself, which differs from that which supplies the liver. The separation of the water is caused by the peculiar internal 216 CIRCULATING FLUIDS: structure of the organ ; it cannot be regarded as a product of the development of tlie cells, or of the metabolic power of the cells acting on the plasma ; but the water is separated in much the same manner as the various gases of the blood are re- moved by the lungs. But Avhether the salts which are separated by the kidneys, the combinations of chlorine, and of phosphoric, sulphuric and lactic acids, are, so to speak, mechanically carried away in the water in which they are held in solution, and which permeates the textures of the kidney, or whether their separation is to be re- garded as a true secretion of the renal cells, due to their organ- ised development, is a point which I have no means of ascer- taining. An accurate analj^sis of the kidneys would soon show whether the salts which have been mentioned do or do not belong to the constitution of the renal cells, a point which the analysis of Berzelius has left undecided. These salts, most of which preexist in the blood, at all events find their way into the renal cells, and either are or are not connected with their peculiar vital development. The former is far the more pro- bable ; and in that case the secretion of the salts would not be a mere mechanical act, but would be due to organic causes. The kidneys separate hoemaphajin from the colouring mat- ter produced by the metamorphosis of the blood-corpuscles, and the proportion in which they separate it is larger than the proportion contained in the plasma, a circumstance which is obvious from the colour of the urine being generally deeper than that of the liquor sanguinis. Hence it is very probable that a portion of the colouring matter is formed by the metamor- phosis of the corpuscles in the peripheral system of the kidney. The kidneys likcAvise separate another colouring matter, uro- erythrin ; in a normal state, only in a slight proportion, but in certain pathological conditions, in a comparatively large quantity. Uroerythrin, in all probability, owes its origin to the hsematin of the blood-corpuscles. As the proportions of uric acid and of uroerythrin to urea are very small in normal lu'ine, but are much increased in certain pathological conditions, we must infer that, in these latter cases, the blood undergoes some peculiar change. BLOOD. 21: Comparison of the venous blood with the blood of the capillaries. It is well known tliat blood taken from the body by scari- fication does not materially differ in its physical properties from venous blood ; it takes about an equal time to coagulate, and separates into clot and serum. The blood which flows from leech-bites is also similar to venous blood. From com- parative analyses of venous blood and blood taken by leeches or cupping. Dr. PaUas^ concludes that the (so termed) capillary blood is richer in solid and coagulable constituents than either venous or arterial blood. The ratios are represented by the following numbers : 2-550 : 3-100 and 2-550 : 2-630 Denis^ contradicts these statements ; he observes that the blood of the capillaries, when taken by cupping, is of a bright red colour and very plastic if it is taken from the neighbour- hood of a large artery, but that it is dark and proportionally less plastic when drawn from the vicinity of large venous trunks; so that its characters always present a certain degree of simi- larity to either arterial or venous blood. Denis analysed blood drawn from the arm of a man aged 70, and blood taken by cupping from the left side of the thorax of the same individual, and compared the results. 1000 parts contained : Blood from the arm. Blood obtained by cupping. Water .... 790-0 790-0 Fibrin 2-7 2-9 Albumen 56-0 54-0 IL-ematin 131-6 133-4 Oxide of iron 0-7 0-7 Phosphorized fat 8-0 8-2 Cruorin M 10 Carbonate of soda 1-0 1-0 Chloride of sodium 4-0 4-0 Chloride of potassium 2-1 2-0 Carbonate of lime 1-3 1-3 Phosphates of lime and magnesia 0-5 0-5 Or, Water .... 790-0 790-0 Blood-corpuscles 132-3 134-1 Solid residue of serum 77-7 75-9 ' Journal de Chimie Medical e, Oc t. 1828. * Recherches, p. 72. 218 CIRCULATING FLUIDS: Denis also analysed the blood of a girl, aged 27, in a similar manner, and obtained corresponding results from both forms of blood. (Recherches, pp. 153, 153, and 250.) REVIEW OF THE MODIFICATIONS AND CHANGES THAT THE BLOOD UNDERGOES IN THE COURSE OF THE CIRCULATION. Having in the previous section given my views respecting the probable changes that the blood undergoes in the course of the circulation, founded partly on numerous analyses of that fluid, and partly on conclusions deduced from the necessary connexion that exists betM-een the phenomena of secretion and of meta- morphosis; and having also endeavoured to explain the varia- tions that occur in the blood of the same individual, through the influence of nutrition and the secreting organs (as the liver and kidneys), I beg once more to call the attention of the reader to the subject under consideration. My views regarding the formation of the products of secretion from the changes that the blood undergoes in the organism re- quire a more searching investigation before confidence can be placed in them. There is nothing improbable in the supposition that the blood is changed in the manner that I have assumed ; I can as easily conceive that the m'ea and bilin are formed by the mutual action of the blood-corpuscles and the liquor san- guinis, as that their origin is dependent upon the liquor san- guinis alone ; but for reasons already communicated, there is a greater degree of probability in the idea that these substances are produced by the metamorphosis of the blood-corpuscles. These reasons are founded more on the intimate connexion that exists between the products of secretion, change of matter and blood, and on the mutual adaptation and principle of compen- sation in the organism of the animal body, than on the phy- sical and chemical "momentum^^ of the circulation and of secre- tion ; and the question we have now to consider is, whether in the latter there is not something directly opposed to our views respecting the metamorphosis of the blood. Before proceeding to these investigations, I must in the first place revert to some of the points connected with this meta- morphic action. The first and principal object of the blood is the nutrition BLOOD. 219 of the organism, and for tliis purpose the circulating fluid is modified and consumed in the peripheral system. We have conjectured that the extractive matters of the blood "which are removed by the kidneys are thus formed. The constant mo- dification and consumption of blood dependent on the act of nutrition render the supply of fresh nutrient fluid, and the re- moval of efl'ete matter, indispensably necessary, since a proper constitution of the blood is requisite for the due performance of the function of nutrition. The effete matters are replaced by chyle mixed with Ipnph ; and this fluid must of necessity be converted into blood, as otherwise the blood would soon consist entirely of chyle. The change is effected by the for- mation of young blood-corpusles, (an act which is accompanied by the consumption of chyle-, lymph-, and oil-corpuscles,) and by the fibrin of the chyle becoming more plastic ; all the other fluid constituents of the chyle are similar to those of the liquor sanguinis, except that there is an excess of water and of ex- tractive matters in the former. If therefore we suppose a con- tinuous formation of blood-coi'puscles, the necessity for their consumption must be sufficiently obvious. I have assumed that fibrin is formed as a consequence of this consumption, and that this newly-formed fibrin supplies the place of that which is em- ployed for the purposes of nutrition in the peripheral vascular system. I have also shown, (page 163,) that there is no diffi- culty in the idea of the formation of albumen; and lastly, I attempted to show that, in all probability, urea, uric acid, and bilin are fonned as a consequence of this consumption of the blood-corpuscles. For these substances must necessarily be formed as products of the changes which the constituents of the blood undergo in the circulation, and are not (as observations on starved and emaciated individuals show us) a consequence of the changes which the circulating fluid undergoes during the nu- trition of the tissues, but are dependent on the metamorphic action that is produced by the respiratory process. It is prin- cipally the blood-corpuscles, (as I have endeavoured to show, in page 155,) that are connected with the consumption of oxygen ; and when we reflect that this change in the corpuscles must take place under similar conditions in animals both high and low in the scale of development, we can understand how it is that urea, luic acid, and bilin occur in the renal and hepatic 220 CIRCULxVTING FLUIDS: secretions of animals of nearly every form of structure, and under sucli varying phases of existence. I will now proceed seriatim with the objections that may be urged against my views respecting the metamorphosis of the blood. Analyses of the urine show us that it contains a greater amount of urea and uric acid than of extractive matters ; as- suming that the former substances, and the bilin, are products of the metamorphosis of the blood-corpuscles, and that the latter are the products of the change that the plasma under- goes in the nutrition of the peripheral system, the mass of the former is greater than the mass of the latter. If, moreover, a portion of the extractive matter is in reality not removed by the kidneys, but is, as I have already suggested, in page 150, again adapted in the circulation to the purposes of nutrition, (serving probably for the C}i;oblastema of the cells of the cartila- ginous and gelatinous tissues), then the separation of so consi- derable a quantity of the product of the metamorphosis of the blood-corpuscles ought still to surprise us, if its only purpose were to supply the fibrin, and possibly a part of the consumed albumen in the plasma. It can, however, be easily shown that another and a much more important final result must be considered in the consumption of the blood-corpuscles. For if, as I have shown, in page 155, the blood-corpuscles are principally concerned in the consump- tion of the atmospheric oxygen, then it is clear that the greater part of the carbon, which is exhaled from the lungs as carbonic acid, must originate from them, and the source of animal heat would thus be chiefly attributable to the metamorphosis of the blood-corpuscles. Consequently, the chemical modifications of the blood-corpuscles are of at least as much importance as the act of nutrition in the peripheral system carried on by the agency of the plasma, inasmuch as they are subservient to the most essential and indispensable requisite for animal life. The other purposes of the corpuscles appear also to be subservient to this great end. If the blood-corpuscles (from the period of their develop- ment up to their final solution) convert as large a quantity of carbon as is generally assumed, into carbonic acid, in order to maintain a proper degree of temperature, then we cannot be astonished at the amount of the products of secretion of the I BLOOD. 221 kidneys and liver, which we have assumed to be consequent on the metamorphosis of the blood-corpuscles ; for since the animal matters undergo a chemical change by the elimination of the carbon, the products which are then formed must be removed, in order that the blood may retain its normal composition. In opposition to the assertion that the urea, uric acid, and bilin are products of the metamorphosis of the blood-corpuscles, it may be m'ged that the daily amount of these secretions in- volves a larger daily consumption of blood-corpuscles than ap- pears to be consistent with the rate of their reproduction, as far at least as our knowledge of the act of formation of the corpus- cles would lead us to infer. I have mentioned, in page 155, that the blood-corpuscles are to be regarded as cells, whose development must be considered as perfectly analogous with the development of other cells. In absorbing from the plasma the substances requisite for their nutrition, and in rejecting the products that must be conse- quent upon the act of absorption, they obviously exert a modi- fj-ing influence on that fluid. The blood-corpuscles do not, however, find their way into the circulating fluid in a matured form, but their c}i:oblasts enter it as germs of the future cor- puscles, and require the assistance of the atmospheric oxygen to attain their perfect development. The only hypothesis we can frame regarding the primary formation of the blood-cor- puscles is, that they are produced from the plasma, that their entire development and increase of bulk is due to the reciprocal action of the young blood-corpuscular cells and plasma on each other at the expense of the latter, and that up to the mo- ment when the blood-corpuscles cease to discharge their func- tions as independent organisms in the circulation, every change that occurs in them must be accompanied by a simultaneous alteration in their cytoblastema, the plasma. It may further be urged that, in order to account for the forma- tion and secretion of urea, uric acid, and bilin, there is no neces- sity for the assmnption that there is a metamorphosis of the blood- corpuscles. These substances might as easily have been formed in the process of chylification, or dui-ing the conversion of the chyle into blood, or from the albumen, instead of from the corpuscles. I have ah-eady mentioned that it is by no means probable that these products of secretion are formed in the act of nutri- 222 CIRCULATING FLUIDS : tion, since they are produced in fasting persons, and even when nearly all the soft tissues are wasted away. We do not, hoAvever, intend to assert that nutrition exercises no influence over these products, or that the peculiar structure of each secreting organ is not to be considered. Neverthe- less I cannot agree with certain physiologists who maintain that in granivorous animals, sugar formed in the chyle is the cause of the carbonic acid evolved from the lungs, or that urea, uric acid, and bilin are formed solely from the albumen, and that the blood-corpuscles take no part in this action ; for the uniform and simultaneous formation of carbonic acid, urea, uric acid and bilin, in animals whose food is so varied, and whose habits and conditions of life are so diversified, renders it pro- bable that these substances are simultaneously formed, as a consequence of one and the same metamorphic act. On the other hand, we must not omit to notice that the occurrence of the non-nitrogenous hippuric acid in the ruminantia, the ex- cessive production of uric acid accompanied frequently with a total absence of urea in birds and amphibia, and the inverse ratio in which these substances occiu' in man, monkeys, &c., as likewise the different chemical relations of the bile in fishes and amphibia, point out the influence of nutrition and of the organization in general on these secretions. Wliat is the ultimate purpose of the blood-corpuscles in the organism if they do not participate in the formation of these products, and if they ex- perience no real material change ? The idea that the nutrition of the tissues is accomplished by the aggregation of blood- corpuscles is now abandoned, and the supposition that these molecules exert a vitahzing influence on the organized tissues is perfectly unintelligible. I can form no conception of a blood-corpuscle that is not undergoing a continuous material change, and I regard this change as the ultimate object of its existence. Daily experience shows us that the fluids which are secreted by the principal glands take their origin from the blood: the question then arises whether these secretions exist in the blood itself, that is to say, whether the blood which enters a secreting organ, as the kidney or liver, indicates a diS'erence of composi- tion as it leaves that organ. At first sight we should doubt- less answer this question in the affirmative; but taking into BLOOD. 223 consideration the rapidity of the circulation, and the short space of time in which the same Ijlood is supposed to remain in an organ, it is obvious that the detection of the changes in the blood, due to the removal of the secretions, will be a task, if not absolutely impossible, at least extremely difficult. The question whether the blood of the same individual pos- sesses anytraceable differences, is most intimately connected with the physico-chemical "momentum^ ^ of the circulation; although sufficient facts and experiments are still wanting to enable the point to be decisively settled, I believe from an estimate of all that is at present kno^^^l on the subject, that we are warranted in the assumption that there does exist a difference in the blood of one and the same individual. According to Hering's experiments, ^ (in which he injected ferrocyanide of potassium into the veins of horses,) the blood performs the circuit of the body in from 20 to 30 seconds. Several authorities are opposed to this statement. It is evident that the blood, as it issues from the heart, proceeds in smaller and larger circles; the smallest are those which it describes through the heart itself and the lungs, the larger are those through the extremities, and it must require different times to go over these different spaces, and besides this, its course is differently impeded in the capillary system of the different or- gans. Thus one portion of the blood may frequently pass through the heart and lungs, while another portion has only made one complete circuit, and traces of the injected ferrocy- anide of potassium which permeates uniformly the whole mass of the blood, may therefore be found after a short time in parts of the system remote from the heart, which have not gone the perfect circuit through the heart, lungs, and all the organs. This appears to be very e^ddent from the fact that some of those salts which are supposed to be rapidly eliminated by the kidneys, may be detected for a considerable period in the blood. Thus I observed,^ that when iodide of potassium was taken at four o'clock in the afternoon, its presence was traceable in the urine till nine the next morning ; and Hering^ found ferrocy- ' Treviranus Zeitschrift fiir Physiologic, 1832, p. 85. ^ Simon, Die Frauenmilcli nach ilirera chemischen und physiologisclieii Verhalten. BerUn, 1838, p. 75. 3 Op. cit. p. 96. 224 CIRCULATING FLUIDS : anide of potassium in the iirinc of a horse two days after it had been injected. Hence the whole mass of the blood occu- pies a considerable time in passing through the renal arteries, or else the kidneys do not remove all the foreign constituents from the blood that passes through them. Others have calculated the rapidity of the circulation by the quantity of blood projected by the heart at each systole. Reck- oning this quantity at from 1 to 2 ounces, and the whole amount of blood in the human body at 30 pounds, it would take from 3 to 7 minutes (assuming the pulse to be 75 in the minute) for all this blood to pass through the heart. Since, however, the blood in the smaller circles passes more frequently tlu'ough the heart in a given time than the blood in the larger circles, and since it is variously impeded and delayed in the different organs, we must not consider that the absolute mass of the blood of the Avhole body is represented by the identical 30 pounds which pass through the heart in from 3 to 7 minutes. The quantity of blood in an adult has likewise never been accurately determined. Hales places it at 25 pounds ; the maximum is, however, calculated to amount to 30 pounds ; and when we consider the extremely large quantity of blood that is retained in the capillary vessels, this estimate is probably too low. That the rapidity with which the blood circulates varies in- versely with the distance from the heart is an established fact. In the capillary system its progress is the most torpid. Omitting the consideration of the various mechanical impediments that meet the blood in the capillaries, it mvist be remembered that, if the blood is the real nutrient fluid of the body, there must be a necessary attraction between it and the organs it has to nourish. The blood in the capillary network permeates the tissues, or (to speak more correctly) the cells of the tissues at- tract from the blood their proper nutriment. It is clear that this must delay the course of the blood in the peripheral sys- tem, to what amount it is impossible to say, but in all proba- bility the delay will vary directly with the intensity of the ac- tion between the blood and the tissues, and with the amount of the change of matter. The greatest delay will most probably occur in the kidneys and in the liver, since they afford the largest amount of secreted matters. Even if the amoimt of the secretions did not indicate a heightened cellular activity, it BLOOD. 225 would be sufficiently proved by the structure of tlie organs themselves, for they are permeated by such an extremely abun- dant and dense capillary network, and such very delicate venous twigs closely encircle their excretory ducts, that the tissue is brought in contact with the blood at eveiy point and in every direction. The chemical constitution of these organs is likewise so pe- culiar, that we might infer that the cells would exert a particu- lar influence; for the muscular tissue, serous membrane, lung, &c. when triturated with water, yield little else than some of the constituents of the blood from the capillary vessels, while the liver and kidneys by trituration yield a pappy mass, which is for the most part soluble in water, contains much fat in a state of suspension, and leaves only a small amount of solid residue (18-9g in the liver, and, according to Berzelius, even less in the kidneys), consisting of shreds of vessels and membranes. From the observations already made, we may infer that the blood vmdergoes a much more rapid metamorphosis in the kid- neys and liver than in the tissues of the muscles, bones, &c. If it were possible to determine the time during which the same blood remains in these organs, then we might decide with some degree of certainty whether the blood which emerges from them differs in its composition from that which enters them. We have seen that there are reasons for assuming that the cumula- tion is delayed in these organs. If we suppose, with Haller,i that the eleventh part of the whole blood passes through the kidnej^s, and that, consequently, at each systole of the heart four scruples are driven into them, then, assuming that the kidneys contain from four to six ounces of blood, and that the rapidity of the circulation in them is the same as in the aorta, the same blood Avill remain in these organs for about one third or one half of a minute. But taking into consideration the various facts that we have adverted to regarding the impeded circulation in these organs, we can scarcely doubt that the blood is detained in them for a very considerable period. According to a calcu- lation made by Keil, and quoted by Hales in his ' Medical Statics,^ the blood remains in the kidneys for several hours. R. Wagner 2 measured the rapidity with which a blood-cor- ' Elem. Phvs., vol. 2, p. 4C7. - Lehrbiicli educed from eight analyses, is given in the following table : Mean. Max. Min. Density of defibrinated blood 1057-5 1060-0 1054-0 Density of serum 1027-4 1030-0 1026-0 Water 791-1 813-0 7730 Solid constituents 208-9 227-0 187-0 Fibrin 2-2 2-5 1-8 Fat* 2-2 5-7 2-0 Albumen .... 70-5 75-5 65-0 Blood-globules 127-2 137-5 113-0 Extractive matters and salts 7-4 8-5 6-2 ' This fat contained : Mean. Max. Min. Serolin 0-020 0-080 inappreciable. Phosphorized fat 0-488 1-000 0-270 Cholesterin 0-088 0175 0-030 Saponified fat 1-004 2-000 0-700 * This fat contained : Serolin 0-020 0-060 inappreciable. Phosphorized fat 0-464 0-800 0-250 Cholesterin 0-090 0-200 0025 Saponified fat 1-046 1-800 0-725 234 CIRCULATING FLUIDS: 1000 parts of the incinerated Chloride of sodium . Other soluble salts . Earthy phosphates . Iron ..... The salts have been analysed (he observes) to 6-28— 6-82;^ of following analyses are given in gischen Chemie :' ood contained : Mean. Max. Mill. 3-90 4-00 3-50 2-90 3-00 2-50 0-35 0-65 0-25 0-54 0-57 0-48 by Marchand. They amount the dried residue. The four his 'Lehrbuch der Physiolo- Chloride of sodium Chloride of potassium Carbonate of soda Sulphate of soda Phosphate of soda . Phosphate of lime . Phosphate of magnesia Lactate of soda Lactate of ammonia 1. 3-91 0-32 0-62 0-31 0-56 0-25 0-21 0-32 0-12 2. 3-42 0-21 0-52 0-52 0-72 0-31 0-20 0-28 010 3. 3-81 0-31 0-72 0-38 0-68 0-28 0-25 0-35 0-00 4. 3-82 0-38 0-61 0-42 0-59 0-30 0-28 0-34 0-08 6-62 6-28 6-78 6-82 In 100 parts of the ash of human blood there are contained, according to Enderlin : Tribasic phosphate of soda (3Na, PO5) Chloride of sodium Chloride of potassium Sulphate of soda Phosphate of hme Phosphate of magnesia Peroxide of iron and phosphate of iron =83-740 soluble salts. 0-769 L =15-175 insoluble salts.] 10-77oJ On the differences of the blood, dependent on sex. Lecanu^ concludes from his analyses that the venous blood of males is richer in solid constituents than that of females, but that the quantity of albumen in both is the same. The follow- ing are the maxima, minima, and mean results of his analyses : Maximum Minimum Mean Maximum Minimum Mean ' Etudes chimiques, etc., p. 65 ; or Journal de Pharmacie, vol. 18, p. 551. Water in venous blood Ditto in that of men. of females. 805-263 853-135 778-625 790-394 791-944 821-764 Albumen in ditto. Albumen in ditto. 78-270 74-740 57-890 59-159 68-080 66-949 BLOOD. 235 Having only made two analyses of the blood of healthy persons, I am not in a position to di'aw any inferences regarding difl'er- ences in its composition, dependent upon sex. I have, however, deduced, from Denis's analyses, a table indicating the differences that exist between male and female blood, at the same age. Blood of Males : Water. Blood-corpuseles. Albumen. Fibrin. Maximum . 790-0 187-1 63-0 2-9 Minimum . 733-3 102-0 52-3 2-1 Mean 758-0 147-0 57-5 2-5 Blood of Females : Maximum . 820-0 162-4 66-4 30 Minimum . 750-0 88-1 50-0 0-25 Mean 773-0 138-0 61-2 0-27 Hence it appears that the analyses of Denis ^ bear out Lecanu's statement with regard to the smaller proportion of water in male than in female blood : the albiunen, however, appears to be rather more abundant in female than in male blood. The proportion of blood-coi'puscles is smaller, and of fibrin rather larsrer than in the blood of the male. [From the analyses of Becquerel and Rodier, it appears that the influence of sex is so great, that, in order to arrive at any correct conclusions respecting the deviation of morbid blood from the healthy standard, diseased male and female blood must be always contrasted with tbe respective male and female blood in a state of health. The mean differences may be seen by a glance at the following table : Male. Female. Density of defibrinated blood 1060-0 1057-5 Density of serum 1028-0 1027-4 Water 779-0 791-1 Fibrin ..... 2-2 2-2 Sum of fatty matters 1-60 1-62 Serolin .... 0-02 0-02 Phosphorized fat 0-488 0-464 Cholesterin 0-088 0-090 Saponified fat 1-004 1-046 Albumen 69-4 70-5 Blood-corpuscles . . . . 141-1 127-2 Extractive matters and salts 6-8 7-4 Chloride of sodium 31 3-9 Otlier soluble salts 2-5 2-9 Earthy phosphates 0-334 0-354 Iron 0-566 0-541 ' Op. cit. p. 290. 236 CIRCULATING FLUIDS: Hence female blood differs materially from the blood of tlie male in the amount of water and of blood-corpuscles.] On the differences of the blood, dependent on constitution. Denis concludes from liis analyses tliat^ generally speaking, the stronger the constitution is, the greater will be the amount of solid constituents, and especially of blood-corpuscles. If age is also taken into consideration, my observations confirm those of Denis. At equal ages, the blood in weak constitutions is less abundant in solid constituents and hsematoglobuhn than in stronger constitutions. On the differences in the blood, dependent upon temperament. According to Lecanu/ temperament has an influence upon the composition of the blood. He infers from his analyses that the blood of lymphatic persons is poorer in solid constituents, and especially in blood-corpuscles, than that of persons of san- guineous temjoerament, while the quantity of albumen is much the same in both. The following table will illustrate these views. 1000 parts of blood contained on an average Men of sanguineous Men of lymphatic temperament. temperament. Water 786-584 800-566 Albumen 65-850 71-781 Blood-corpuscles 136-497 116-667 Women of sanguineous Women of lymphatic temperament. temperament. Water 793-007 803-710 Albumen 71-264 68-660 Blood-corpuscles 126174 117-300 On the differences in the blood, dependent on age. My own observations, which, however, chiefly refer to dis- eased blood, lead to the conclusion that the blood of young persons contains a larger proportion of solid constituents, and especially of blood-corpuscles, than that of older persons. Lecanu and Denis have, however, made this a point of especial inquiry, and have extended their analyses over a wide range of ages. ' Op. cit. p. 66. BLOOD. 237 I have drawn up the following table from the numerous analyses of Denis^ the blood being considered healthy. 1000 parts of healthy blood of males contained : Age. Water. Solid residue. Fibrin. Blood-corpuscles. Albumen. 14 years. 750-4 249-6 4-0 1G2-2 58-0 23 733-0 2070 2-3 182-9 55-0 25 732-0 2G8-0 2-5 181-4 60-0 31 766-0 234-0 2-1 150-1 62-2 33 783-0 217-0 2-9 129-3 600 40 7500 250-0 2-5 167-8 55-1 46 769-0 231-0 2-5 156-9 48-5 50 748-0 252-0 2-5 170-9 55-0 53 7900 210-0 2-6 100-0 63-0 54 7980 202-0 3-0 111-0 63-0 65 800-0 200-0 31 114-8 60-0 70 790-0 2100 2-7 132-3 56-0 80 781-0 219-0 2-5 130-4 61-0 1000 parts of healthy blood of females contained : 4 833-0 167-0 2-8 80-5 640 6 820-0 180-0 2-5 97-6 59-0 12 7870 213-0 23 130-0 57*0 15 774-0 226-0 25 135-7 65-0 20 772-0 2280 2-5 144-2 57-0 22 780-0 220-0 2-5 133-4 60-0 32 7500 250-0 3-0 1734 51-0 38 774-0 226-0 2-7 131-5 68-4 48 786-0 2140 3-1 1260 60-0 52 820-0 180-0 2-9 88-1 680 74 745-0 255-0 2-5 1711 55-0 It appears from these tables, especially from the second, that the blood is less abundant in solid constituents, and par- ticularly in blood-corpuscles in early life, than at the period of maturity. From the latter period (or rather sooner) to middle life the proportions of the corpuscles and of the solid constitu- ents continues large ; from that time to an advanced age they are subject to a decrease. [Becquerel and Rodier observe that, after the age of 40 or 50, there is a decided and progressive in- crease of cholesterin in the blood.] Denis has made a comparative analysis of the blood of the mother and of the foetus ; he found that the latter was richer in solid constituents and in blood-corpuscles than the former. 238 CIRCULATING FLUIDS The two following analyses, one of the venous blood of the mother, the other of the placental blood as it issued from the artery of the cord, may serve as an additional illustration of the point. The blood of the umbilical artery was of a brown-red colour, smelled of the liquor amnii, and became of a brighter coloiu" on being exposed to the air. Venous blood of Blood of mother. umbilical artery Water . 781-0 701-5 Solid residue . 219-0 298-5 Fibrin 2-4 2-2 Albumen 50-0 50-0 Blood-corpuscles 139-9 222-0 Peroxide of iron 0-8 20 Phosphorized fat 9-2 7-5 Ozmazome and cruorin 4-2 2-7 Salts 12-5 12-1 The difference in the solid constituents and in the blood- corpuscles is obviously very considerable ; the same is the case with the iron, the ratio being 1 to 2*5. The mass of the blood in the foetus increases in a very rapid ratio with the development. The proportion of corpuscles is more augmented, and the quantity of water is less than occurs at any subsequent period of life. Even for some time after birth the mass of the blood is relatively large, and the propor- tion of blood-corpuscles and of iron contained in them is con- siderably above the ordinary standard. Denis has made some experiments on the difference between the blood of very young animals and those of matm'e age, which confirm the observations already made. His experi- ments were instituted on dogs. Water .... Blood of a dof;, 3 months old. 830-0 Blood of a puppy, 1 day old. 780-0 Solid residue 170-0 220-0 Fibrin .... 2-4 2-0 Albumen 58-6 46-0 Blood-corpuscles Extractive matter and salts 97-0 120 1C50 7-0 When the skin of the new-born animal loses its red tint, the blood becomes more watery, the blood-corpuscles and the quantity of iron are diminished, and it becomes relatively, but BLOOD. 239 not absolutely, poorer, for its quantity at the same time in- creases. Subsequently, however, Avlien tlie generative powers begin to be developed, the corpuscles and the iron increase, and the relative proportion of Avater diminishes. At the period of fiiU development the excess of corpuscles and iron serve in maintaining the necessary energy of that part of the system, and till the generative powers begin to flag the blood remains abundant in solid constituents, and more especially in corpuscles. These observations are suggested by the results obtained by Denis, 1 as will be clearly seen by the following taljle, which was drawn up by that chemist himself. The mean amount of solid constituents and of blood-corpus- cles at difierent ages ai'e given in the following proportions. Solid constituents. Blood -corpuscles. a 5 individua Js between 5 month s anc I 10 JTS. 170 11 13 , 10 years and 20 yrs. 200 14 11 20 30 240 17 12 30 40 240 17 6 40 50 240 17 8 50 60 220 15 2 60 70 210 14 The following table shows that Lecanu^s analyses confirm those of Denis and myself. Age. Water. Solid residue. Blood-corpuscles. Albumen 26 778-625 221-375 146-885 62-949 30 788-323 211-677 131-688 71-061 34 795-8/0 204-130 115-850 78120 38 783-890 216-110 148-450 67-890 45 780-210 219-790 132-820 72-970 48 805-263 194-737 117-484 65123 62 801-871 198-129 121-640 65-389 ON DISEASED BLOOD. The pathological chemistry of the blood. The question whether there exists such a thing as diseased blood is easily answered. The material deviations from its normal condition exhibited by the blood in its physico-chemical relations, in certain morbid conditions of the system, have long been recognized by pathologists. 1 Reclierches, pp. 289, 290. 240 CIRCULATING FLUIDS: The quantity of the fibrin is sometimes found to be very much increased, while in other cases it is present only in such very small proportions that no clot is formed. The blood will sometimes be found to be very rich in solid constituents, and especially in blood-corpuscles ; while at other times it will be so poor as to resemble coloured water. In some instances the corpuscles will sink rapidly in whipped blood ; while in others they will only deposit themselves slowly and imperfectly, so that merely a thin layer of serum remains above them. It will also sometimes contain substances which are not found in it in a nor- mal state, as colouring matter of the bile, sugar, or urea. All these are deviations from the normal state of the blood; and if we term that blood healthy, which is constituted in the ordinary manner, and properly discharges its various functions, we are perfectly justified in considering blood as diseased which does not fulfil these conditions. The analyses published by Andral and Gavarret,i in their elaborate essay upon this subject, correspond in their results, generally speaking, with those instituted by myself. They, however, usually assign a higher proportion to the corpuscles (especially in the blood during inflammatory diseases) than I have found to occur. It is hardly probable that such diff'erences should arise from the geographical positions of the observers, although, generally speaking, the blood may be richer in solid constituents and in corpuscles, in southern than in northern regions : it is more likely that they are caused by the different methods of analyses pursued by the French observers and my- self. I have tried both methods, and consider it useful, if not necessary, to state the results of my trial. In the analyses of Andral and Gavarret, the blood is received into two six-ounce vessels. The first and fourth quarters are received in one vessel, the second and third in the other. In one, the blood is allowed to coagulate spontaneously ; in the other, it is whipped, in order to obtain the fibrin, which must be carefully washed. When the coagulation is efiected, the clot must be carefully removed from the serum, and we must dry (a) the fibrin which has been obtained hj whipping one portion of the blood ; {/j) the serum ; and (c) the clot. By weighing ' Amial. dc Cliimic et dc Phys. vol. 75, p. 225. BLOOD. 241 the dried fibrin we know the quantity of that constituent con- tained in the clot. By weighing the dried serum we know the proportions of water and of soHd constituents contained in it. Lastly, we weigh the dried clot : the quantity of water which it gives off is estimated as serum, and the solid residue due to it is readily calculated. By deducting from the weight of the dried clot the weights of the fibrin and of the solid residue of the serum contained in the clot, we obtain the amount of the globules. Hence we have (1) the weight of the fibrin; (2) the weight of the globules ; (3) the weight of the solid residue of the serum ; and (4) the weight of the water. This method is simple, and easy of application, in cases in which it is unnecessary to ascertain the proportions of hsematin, globulin, fat, hsemaphsein, extractive matters, and salts, sepa- rately. I shall, however, show that an error may easily arise in the determination of the blood-corpuscles, if the drying has not been perfectly effected. In order to ascertain what would be the amount of difi'erences, I analysed the same blood by their method, and by my own. About eight ounces of blood were received in a glass, from the arm of a woman, aged 35 years. It was rapidly stirred ; about a fourth part of it was poured into a small glass, and the fibrin removed in the ordinary manner, by whipping. The larger portion was left to coagulate. I. Analysis of the defibrinated blood. The blood, including the fibrin, weighed 950 grains, of which the fibrin, when washed and thoroughly dried, weighed 1"9 gr. Hence 1000 parts of blood contain 2"0 of fibrin. 112-42 grains of defibrinated blood left, after the thorough removal of the water, a solid residue, amounting to 2033 grs. Hence 1000 parts of blood contained 180 of solid constitu- ents ; 7'7 grains of the dried residue were boiled in spirit of •925, to which three drops of dilute sulphuric acid were subse- quently added, as long as the spirit continued to take up any- thing more, and until a bright gray-green residue was left. This residue, which is composed of the albumen of the blood, when dried, weighed 3"31 grains. The red alcoholic solution was saturated with ammonia, and evaporated to a small residue. The hsematoglobulin, which se- 16 242 CIRCULATING FLUIDS: parated perfectly in this way, was then washed several times with water, dried, and weighed. Its weight amounted to 4 grains. The extractive matters and salts (including loss) may therefore be estimated at '39 of a grain. Now since 1000 parts of the defibrinated blood contain 180 of solid residue, the blood must contain : Water 818-00 SoUd residue 182-00 Fibrin 200 Albumen ..... 77-40 Ilaematoglobulin .... 93-GO Extractive matters, salts, and loss . 9-00 1000-00 II. Analysis of coagulated blood, according to the method of Andral and Gavarret. a. The serum weighed 1406 grains. b. The clot weighed 1228 grains. In order to ensure a greater degree of accuracy in my re- sults, I evaporated only a portion of this quantity. 375-14 grains of the clot when dried, cautiously pulverised, and again heated, left 112*54 grains. Hence 100 parts of the clot contained 30-0 of solid constituents. 449-98 grains of serum left 42*66 of solid residue, which corresponds therefore with 9-55. 1000 parts of blood consist of 533*8 of serum and 466*2 of clot, of which the serum gives a residue of 50*7, and the clot of 139-86 parts. The solid residue of 1000 parts amounts there- fore to 190-56. From the residue of the clot we deduct 2-0 for fibrin, and 31*0 for the solid residue of the serum contained in it, which must be added to the 50*7. Consequently 1000 parts of blood contain : Water Solid residue Fibrin Solid residue of serum Blood-corpuscles 809-44 190-56 2-00 79-70 108-86 1000-00 BLOOD. 243 The differences between these analyses are obvious. The solid constituents obtained by Andral and Gavarret's method are 8'5 higher, in 1000 parts of blood, than by mine ; moreover, the quantity of corpuscles obtained by them considerably exceeds the haematoglobulin separated by my method. If we assume that the 8*5 parts of water which Andral and Gavarret^s method did not succeed in removing, were retained in the clot, the cor- puscles would be reduced from 10886 to 98'3 ; in which case the discrepancy between the two analyses would be much less striking. 1000 parts of blood would then contain : According to Simon. Fibrin .... 2-00 Albumen, with extractive matters, and salts . . . 86-40 Haematoglobulin . . 93-60 According to Andral and Gavarret. Fibrin .... 2-00 Solid residue of serum . 80-50 Blood-corpuscles . . 99-50 It must, however, be remarked, that the sum of the haematin and globulin, in my analyses, can never represent the absolute quantity of blood-corpuscles. As has been previously remarked, the nuclei and capsules of the blood-corpuscles have been esti- mated as albumen by my method, as fibrin by Berzelius, and as appertaining to the corpuscles by Andral and Gavarret. Their absolute weight has never been accurately ascertained,' but it cannot be larger, since the quantities of fibrin obtained by washing the clot, and by whipping fresh blood diflfer very little. Further, a portion of fat separated by my method, be- longs to the blood-corpuscles, and we cannot deny the possi- bility of the corpuscles containing albumen. My analyses, moreover, aim not merely at the determination of the proportion of the fibrin, of the corpuscles, and of the solid residue of the serum, but they are intended to embrace the determination of the most important proximate constituents of the blood ; and if the haematoglobulin, or possibly the glo- bulin be regarded as constituting the principal mass of the cor- puscles, I can succeed in tracing their increase or decrease by means of the proportion of the haematoglobulin or globulin. The following objections may likewise be brought against Andral and Gavarret^ s method. ' Nasse (Das Blut in raehrfacher Beziehung, &c., Bonn, 1836, p. 109) has attempted to form a quantitative analysis of the nuclei. 244 CIRCULATING FLUIDS : In cases where no consistent clot is formed, but where there is merely a slight gelatinous coagulation, as frequently occurs in blood deficient in fibrin, the serum and the clot cannot be separated with any degree of exactness. If the clot be allowed to stand for some hours in order to induce a more perfect se- paration of the serum, the water partially evaporates, and the ratio of the solid constituents of the clot to the water becomes changed, and consequently too high a number is assigned to the corpuscles. The difficulty of thoroughly removing the water varies in a direct proportion with the quantity of the blood submitted to evaporation. Serum, comparatively poor in solid constituents, gives only a slight residue, from which the water can be more readily expelled, than from the more abundant residue left by the clot : in proportion to the water remaining in the clot, the quantity of corpuscles found by this method will be increased, as wiU be clearly seen by the following illustration. 1000 parts of blood are composed of 500 parts of serum and 500 of clot. The serum leaves a solid residue of 50, or 10^; the clot of 150, or 30«. The 350 parts of water in the clot are to be estimated as serum, and thus give a residue of 35 parts; so that 1000 parts of blood, (the fibrin not being taken into consideration) consist of: Water 800 Solid residue ... 200 Blood-corpuscles . . . 115 Residue of serum . . . 85 If, however, the clot had not been perfectly dried, and if only 1 per cent, of water in relation to the weight of the whole blood had been retained, we should have obtained the follow- ing result : 500 parts of clot would then give 160 of sohd residue, and there would therefore be 340 of water, which, estimated as serum, would yield 34 of residue ; consequently the corpuscles would be estimated at 126, and 1000 parts of blood would consist of: Water 790 Solid residue . . . 210 Blood-corpuscles . . , 126 Residue of serum . . . 84 BLOOD. 245 In all other methods of analysing tlie blood in which the water is determined by a separate process, and the dried residue is used for further investigation, an error in its estimation will simply increase the absolute quantity of the solid constituents, without disturbing their relative proportions. But in the ap- plication of their method it is easy to see that each per-centage of retained water not only increases the absolute quantity of the solid constituents to the amount of 1^, but also the weight of the corpuscles, not only by the addition of the retained water, but also by the weight of the residue of the serum, due to an equal quantity of water, and which amounts to 1*1^. Moreover, the supposition of Andral and Gavarret, that the humidity of the clot shovild be considered as serum is totally devoid of foundation. The corpuscles cannot be supposed to swim in the plasma as dry molecules, and it has not been proved that the fluid, with which they are filled, is the fluid of the serum. These observations are sufficient to show that Andral and Gavarret's method, and my own, give somewhat different re- sults: the difi'erences, however, are not very material, and are easily explicable on the grounds abeady stated. The changes which the composition of the blood may expe- rience in its various pathological conditions, are either de- pendent upon the quantity of solid residue generally, or upon the changed relative proportions that the various proximate constituents bear to each other. If we assume the composition of healthy blood, (as deduced from the mean of my analyses) to be represented by Water Solid residue Fibrin Fat Albumen Globulin Haematin Extractive matters and salt 795-278 204-022 2-104 2-346 76-600 103-022 6-209 12-012, the following difi'erences will be found to occur among the specimens of diseased blood which I have analysed. The quantity of — 246 CIRCULATING FLUIDS: Water . may vary from 888-0 to 750-0 Solid residue „ 250-0 112-0 Fibrin 9-1 a trace Fat 4-3 0-7 Albumen 131-0 55-1 Globulin 106-6 30-8 Hsematin 8-7 1-4 Ha^matoglobulin . 115-4 31-2 Extractive matters and salts „ 16-5 7-6 The analyses of the French chemists gave the following results, with regard to this subject. Taking the mean of Lecanu^s analyses of healthy blood as a standard, and contrasting with it the extreme results which were found by Andral and Gavarret in diseased blood, we have the following results: Lecanv!s Analysis. Water 790 SoUd residue ... 210 Fibrin .... 3 Organic residue of serum . 72 Inorganic ditto ... 8 Blood- corpuscles . . . 127 Andral and Gavarrefs Deviations. Water from 915-0 to 725-0 Solid residue . » 275-0 85-0 Fibrin » 10-5 0-9 Solid residue of serum „ 114-0 57-0 Blood-corpuscles »> 185-0 21-0 From these data, it appears, that although the proportions of all the constituents are subject in disease to a certain amount of change, the variation is the most striking with regard to the fibrin and globulin. The former is found in my analyses occasionally to exceed four times the average quantity, and in Andral and Gavarrefs, three and a half times ; while the latter may diminish, accord- ing to my analyses, to a mere trace; and according to Andral and Gavarret^s, to one sixth of the normal quantity. These determinations must not, hoAvever, be regarded as ab- solute : they are dependent on various causes, and can be ex- plained in more ways than one. BLOOD. 247 For instance^ the 21 parts of blood-corpuscles were observed by Andral and Gavarret in blood which left a residue of only 85, while the 185 of corpuscles occurred in blood which gave a residue of 275. Hence the per-centages of the corpuscles in these two cases, in regard to the solid residue, are 26"^ and 67^ respectively. The deviations in the proportions of the various constituents do not occur singly, for instance, we do not find the other con- stituents in normal proportions, and the blood-corpuscles alone very low ; neither are they all found simultaneously deficient or in excess : but there exists, as we shall soon see, a certain an- tagonism between the proportions of the individual constituents. Thus we find that when the fibrin is much increased, the cor- puscles are diminished in quantity, and vice versa. In every 100 parts of the residue of healthy blood, we have 1 of fibrin and 53 of h^ematoglobulin. In diseased blood I have observed the following proportions : ibrln. Haematoglobulin 1-4 43 1-6 40 1-7 40 20 42 20 39 2-1 36 30 28 60 22 A similar relationship is exhibited in the analyses of Andral and Gavarret; the range of the corpuscles is, however, not so extensive. Fibrin. Blood-corpuscles Healthy blood 1-5 Gl Diseased blood 2-5 60 3-2 57 41 57 4-2 54 4-8 52 5-0 50 The connexion between the fibrin and blood-corpuscles is still more strikingly exhibited in some of the analyses of Andral and Gavarret, in which blood was taken several successive times 248 CIRCULATING FLUIDS from the same patient, tration : We select four cases by way of illus- Veneaectiun . Fibrin. Blood- corpuscles. Fibrin. Blood- corpuscles. Fibrin. Blood- corpuscles. Fibrin. Blood- corpuscles 1st 6-3 130 6-1 123 40 Ill 5-6 133 2d 7-7 106 7-2 120 5-5 107 5-5 131 3d 8-2 112 7-8 112 6-5 101 9-1 128 4th 9-3 103 10-2 101 9-0 83 9-4 102 In the following table drawn up from Andral and Gavarret's analyses^ the first column gives the j)roportions of fibrin and of corpuscles in 100 parts of solid residue. The second column does the same, only that in this case the quantity of fibrin is considered constant, and is represented by 1"5, and the propor- tion of corpuscles is estimated accordingly : an arrangement which makes their increase more obvious. Fibrin. Corpuscles. Fibrin. Corpuscles Healthy blood 1-5 61 1-5 61 Diseased blood 1-5 64 1-5 64 >» 1-5 65 1-5 65 r> 1-3 60 1-5 69 « 11 53 1-5 72 >» 1-2 59 1-5 74 » 11 60 1-5 81 n 10 60 1-5 90 „ 0-9 60 1-5 90 n 1-0 61 1-5 91 „ 1-0 64 1-5 96 n 0-9 63 1-5 105 M 0-5 60 1-5 180 [Becquerel and Rodier have laid it down as a general law that " bleeding exerts a remarkable influence on the composition of the blood, the greater the oftener the bleeding is repeated.^' The three following tables show the mean results of the first, second, and third venesections, performed on a certain number of Cruveilhier's patients. Ten patients were bled twice, and ten thrice, so that we have 20 first, 20 second, and 10 third bleedings. BLOOD. 249 Mean composition of the blood of twenty pei'sons bled ttvice. 1st Venesection. 2d Venesection. Density of defibrinated blood 10550 1051-2 Density of serum 1026-1 1025-3 Water .... 796-2 812-0 Solid residue 203-8 188-0 Fibrin .... 3-7 3-8 Albumen 66-2 62-5 Blood-corpuscles 125-4 112-0 Extractive matters and salts 6-8 7-6 Fat .... 1-657 1-560 Consisting of — Serolin 0-027 0-047 Phosphorized fa t 0-490 0-465 Cholesterin 0-178 0-150 Saponified fat 0-962 0-900 The salts in 1000 parts of blood were : Chloride of sodiimi 2-8 3-4 Other soluble salts 2-7 2-5 Phosphates 0-435 0-417 Iron .... 0-527 0-488 Mean composition of the Moot I of ten persons bled three times. 1st V enesection. 2d Venesection. 3d Venesection Density of defibrinated blood . 1 056-0 1053-0 1049-6 Density of serum . . . ] 028-8 1026-3 1025-6 Water 793-0 807-7 833-1 SoUd residue .... 207-0 192-3 176-9 Fibrin 3-5 3-8 3-4 Albumen .... 65-0 63-7 64-6 Blood-corpuscles 129-2 116-3 99-2 Extractive matters and salts 7-7 6-9 8-0 Fat . . . . 1-662 1-584 1-530 Consisting of — Serolin 0-026 0-088 0012 Phosphorized fat 0-637 0-489 0-450 Cholesterin 0-106 0-156 0-149 Saponified fat 0-893 0-851 0-919 The salts contained in 1000 parts of blood were : Chloride of sodium 2-8 3-5 3-0 Other soluble salts 2-6 2-5 2-7 Phosphates .... 0-404 0-493 0-348 Iron 0-J )13 0-471 0-468 From these tables they draw the following conclusions. "In proportion to the number of venesections the blood becomes im- poverished and more watery; hence the fall in the density of the defibrinated blood. The albumen diminishes^ but only slightly; 250 CIRCULATING FLUIDS: hence tlie density of the serum is not much affected. The fibrin is quite uninfluenced by venesection, and its amount is determined by the nature and intensity of the disease. The extractive matters and salts are unaltered. There is a slight diminution in the amount of fat. The various salts are un- affected, and the iron, in consequence of its relationship to the corpuscles, is diminished. In short, the effect of venesection is to cause a great diminution of the corpuscles, while it only slightly lessens the amount of albumen.^^] THE FIRST FORM OF DISEASED BLOOD, HYPERINOSIS.l Chemical characters of the blood. The blood contains more fibrin than in the normal state, and the corpuscles decrease in proportion to the excess of fibrin; the fat is also increased. In proportion to the increase of the fibrin and fat, and the decrease of the corpuscles, the whole solid residue will be diminished.^ Physical characters of the blood. The blood coagulates more slowly than in the normal state ; the clot is usually not small, but very firm and consistent, and does not break up for a considerable time. It is almost in- variably covered with a true buffy coat, (which is produced by the sinking of the corpuscles before the occurrence of coagu- lation, and by the subsequent coagulation of the fibrin in the layer of serum. )^ This buffy coat is firm, tough, and intimately connected with the clot; its edge is often turned upwards, and its surface uneven.^ If the clot is small, the bufly coat and ' Derived from inrtQ and l', Ivoq, the fibre of flesh. 2 Nasse (Das Bhit in mehrfacher Beziehuug, &c.) has arrived at similar conclusions ; for he observes that the corjjuscles and the fibrin are generally in an inverse ratio, and that blood exhibiting a decided genuine buff'y coat is usually of low specific gravity, that is to say, the amount of water is increased. ^ [The bufiy coat does not consist of true fibrin, but of the binoxide and tritoxide of protein. (See page 10.)] ■• The buffy coat is not exclusively connected with an inflammatory state of the blood ; it occurs in other diseases, as, for instance, in chlorosis, but its properties are then very diflferent. A very elaborate disquisition on the formation, and the proximate and remote causes of the bufiy coat, occiu-s in Nasse's work, pp. 36-57' and 204-240. i BLOOD. 251 the surface of the clot are more or less cupped ; the serum is of a pure lemon colour, not tinged red. When subjected to whipping, the fibrin separates in thicker and more solid masses than in ordinaiy blood. After the removal of the fibrin the corpuscles quickly sink, and frequently occupy only one fourth of the whole fluid, while, in healthy blood, they sink very im- perfectly or not at all. The blood has always an alkaline re- action, and is of a higher temperature than in the ordinary state. Laueri found the temperature of the blood in pneumonia as high as 100°, and in bronchitis it reached 101°-6. These tem- peratures are, however, not higher than are met with in healthy blood. According to Becquerel the temperature may rise to 5°-4 in inflammatory diseases and fevers. According to Coupil it amounts, in inflammatory disorders, to 106° — lll°-7, and at the inflamed region to 112°-4<. The microscope has not yet succeeded in detecting any con- stant pecuHarities. The blood occurs in a state of hyperinosis in all inflamma- tory disorders (Phlogoses). In proportion to the firmness of the clot, the concavity of its surface, (the cupping,) and the toughness, and thickness of the bufly coat, is the degree of inflammation; and conversely the thinner and more friable the clot is, the less intense is the dis- order. We also find, accompanying these physical symptoms, an excess of fibrin, and a diminution of hsematoglobuhn, as well as of the solid constituents of the blood generally, and in proportion to the degree in which these phenomena are ob- served, we may infer a greater or lesser amount of inflammatory action. [Before proceeding to the consideration of individual dis- eases, we may observe that Becquerel and Rodier have deduced the following law from their numerous analyses of morbid blood. "The development of an inflammatory disorder pro- duces remarkable modifications in the composition of the blood, of which the most striking is the increase of fibrin.^^2 ' Quffidam de saugiiiiiis different, in Morb. p. 15. = The authors merely regard this as a confirmation of the law established by Andral and Gavarret, not as an original discovery. 252 CIRCULATING FLUIDS: The following table, extracted from their memoir, gives the mean results obtained from the analyses of blood in a number of cases of well marked inflammation. Density of defibrinated blood Density of serum Water Solid constituents Fibrin Albumen Blood-corpuscles Extractive matters and salts Fat ... Consisting of — Serolin Phosphorized fat Cholesterin Saponified fat Males. 1056-3 1027-0 791-5 208-5 5-8 66-0 128-0 7-0 1-742 0-020 0-602 0-136 0-984 The salts in 1000 parts of blood were : Chloride of sodium .... 3"1 Other soluble salts .... 2*4 Phosphates 0-448 Iron 0-490 Females. 1054-5 1026-8 801-0 199-0 5-7 65-8 118-6 7-2 1-669 0-024 0-601 0-130 0-914 3-0 2-7 0-344 0-480 By a comparison of these results with the formulae for healthy blood, (vide supra, p. 233,) we see that only three constituents, fibrin, cholesterin, and albumen, deviate from the normal standard. The first two of these constituents are increased, the last is diminished.] I. PHLOGOSES OF THE CIRCULATING SYSTEM. a. Metrophlebitis puerperalis. In most of the cases of metrophlebitis puerperalis that have occurred in our lying-in institution as well as in the hospital, the blood exhibited all the symptoms of hyperinosis. Accord- ing to Ebert's observations the clot was rather large, and so consistent that sections of it still displayed a powerful and well-marked tenacity. The surface, which was more or less con- cave, was either covered with a thin true huffy coat, or more fre- quently, with a rather thick, and often discoloured stratum of gelatinous substance, forming, what is termed, a false bufty coat. Gelatinous coagula, of a similar nature, were also fre- quently seen floating in the serum. BLOOD. 253 The microscope often detects pus in the blood, during the course of this disease. If, however, the quantity of pus is only small, its detection may be attended with much diffi- culty.^ As the presence of pus in the blood has also been recognised in other pathological conditions, and many obser- vations have recently been made upon the subject, I shaU refer to this point more particularly when I speak of the presence of foreign substances in the blood. I have analysed the blood of two women suffering from me- trophlebitis puerperahs. The analyses gave : Analysis 15. Analysis 16. ^yate^ 836-360 785-560 Solid residue 163-640 214-440 Fibrin 7-640 4-440 Fat 3120 4-320 Albumen 103-358 112-770 Globulin 40-000 74-130 Hsematin 2-080 3-440 Extractive matters and salts 7-649 12-390 100 parts of bjematoglobulin con- [ 100 parts of hsematoglobulin con- tained 5-0 of colou iring matter. 1 tained 4-6 of colouring matter The blood in analysis 15 was taken from a woman aged 20 years, who was attacked in om- Ijdng-in institution with violent phlebitis uterina the day after her delivery. The pulse was full and hard, and 140 in the minute, previous to the bleed- ing. The post-mortem examination revealed a high degree of inflammation of the veins and of the uterus itself, with a co- pious deposition of pus. In analysis 16, the blood was taken from a woman aged 20, Avho was seized fourteen days previously to the bleeding with a violent attack of phlebitis uterina, from which, however, she recovered by the use of venesection and mercuiy. Violent fever afterwards came on, accompanied by pain in the region of the uterus. The pulse was somewhat full and hard, and 132 in the minute. She died soon after, and the post-mortem examination proved the accuracy of the diagnosis. [In a case of plegmasia alba dolens, accompanied with fever, occurring in a woman aged 21 years, six weeks after deliver\% ' According to Gendrin, when there is pus in the blood, the serum deposits a viscid urinary-like sediment, or else is turbid and cloudy. 254 CIRCULATING FLUIDS : Becquerel and Rodier found a considerable diminution of the blood-corpuscles (92"6J and an augmentation of tlie fibrin (4?'2.) The cholesterin was in excess^ ("223^) and the phosphates were abundant.] |3. Carditis. Lecanui analysed the blood of three men and five women, who were suffering from angiocarditis and endocarditis. Un- fortunately he has made no observations on the physical cha- racters of the blood, and the quantity of fibrin was also not ascer- tained. The analysis seems to have consisted simply in the separation of the clot from the serum, and then ascertaining the solid residue of each. The blood of men gave the follo^ving results : Water. Solid residue. Residue of serum. Blood-corpuscles. 1 821-02 178-98 77-59 101-39 2 880-48 119-52 77-62 41-90 3 807-27 192-73 96-35 96-38 The blood of women gave : 4 873-45 126-55 86-10 40-45 5 868-62 131-38 79-89 51-49 6 866-61 133-39 89-69 43-70 7 877-51 122-49 77-00 45-49 8 845-14 154-86 85-80 ^906 Healthy blood 790-00 210-00 80-00 130-00 It is much to be regretted that the fibrin was not deter- mined in these researches, as the proportions of the solid re- sidue, and especially of the corpuscles, indicate a high degree of h^'perinosis. Blood taken by repeated venesections from the same patient during carditis, differs in the follo\^'ing respect fi'om blood simi- larly taken in cases of bronchitis, pneumonia, peritonitis, rheu- matism, &c. ; in these latter it becomes gradually poorer in solid constituents, and especially in coi'puscles, while in the former, at least if we may judge from two analyses of Lecanu, the reverse takes place. The man whose blood formed the object of the second analysis, on venesection being repeated 12 hours afterwards, yielded blood which left a solid residue of 139*1, and the woman from ' Etudes cliimiqiies, etc., ]). 110. BLOOD. 255 whom the blood in the eighth analysis was derived yielded, on a repetition of the venesection, blood which contained : Water .... 841-62 SoUd residue . . . 158-38 Residue of serum . . 81-/9 Blood-corpuscles . 76-58 Lecanu noticed in the blood of one of these men a solid floating mass, (which, when dried, weighed about 100 grains.) It had a fleshy appearance, and on a section being made it ex- hibited a sohd, loosely attached nucleus, of a brick-red colour, in the centre, which slowly dissolved in water. On the second occasion of this patient being bled, the clot presented even a more singular appearance. It was almost entirely formed of agglo- merated clusters of small, round, white, grape-like masses, which were composed centrally of a bright red gelatinous substance. [In a case of pericarditis with efiusion, occurring in a woman aged 40 years, in which the blood was analysed by Becquerel and Eodier, the following results were obtained : 1st Venesection. 2d Venesection. 3d Venesection. 1045-8 1042-4 1045-5 1023-0 1021-8 1024-3 831-0 847-0 169-0 153-0 2-3 2-3 3-4 1-094 1-094 53-0 51-0 60-4 105-0 92-0 78-0 Density of defibrinated blood Density of serum Water Solid constituents Fibrin Fat Albumen Blood-corpuscles In the first analysis the phosphates were in excess (0-684); in other respects the salts occurred in their normal proportions. At the period of the third venesection, the heart-sjTuptoms were much alle\dated. The most remarkable featme in this blood is the extreme diminution of the albumen. There was no albumen in the urine.] II. INFLAMMATION OF THE RESPIRATORY ORGANS. a. Bronchitis. The blood usually exhibits, at least when the symptoms are at all urgent, decided indications of hyperinosis. The buffy coat is scarcely ever absent, the serum is clear, and the clot 256 CIRCULATING FLUIDS: firm and consistent. The fibrin and fat are always more or less increased, and the hsematoglobulin diminished. Analysis 17. Analysis 18. Water .... 797-500 757-831 Solid residue . . . 202-500 242-269 Fibrin .... 4-320 Fat .... 3-650 3-393 Albumen . . . 96-890 109-080 Globulin . . . 76-530 106-650 Hcematin . . . 3-200 8-762 Extractive matters and salts 11-560 14-500 100 parts of b.-ematoglobulin con- 100 parts of haematoglobulin con- taiued 4-0 of colouring matter. tained 8-4 of colouring matter. In analysis 17 we observe, in a decided degree, the character of inflammatory blood, as far as regards the large quantities of fibrin and fat. The quantity of haematoglobulin, 79-73, is not so much diminished in proportion to the albumen in this case, as in those of phlebitis uterina. The patient was a robust man, of about thirty years of age, who had only been suff'ering from the disease three days; pulse hard and very frequent. The blood of analysis 18 was taken from a child three years of age, by leeches, which is the reason why the fibrin was not determined. Andral and Gavarret^ have analysed the blood in six cases of bronchitis, and in all the instances in which fever was present, they found that well-marked character of inflamed blood, an increased quantity of fibrin. The maximum was 9*3, the mi- nimum 5-7, in 1000 parts of blood. I shall now give the results of their analyses. Venesection. Water. Solid residue. Fibrin. Blood-corpuscles. Solid portion of serum 1st Case 1 ^ l2 763-3 793-6 236-7 206-4 7-3 9-3 148-8 110-2 80-6 86-9 2d Case 1 789-6 210-4 6-3 117-6 rganic. 78-0 inorganic. 8-5 3d Case | ^ 769-5 230-5 5-9 139-6 76-7 8-3 782-2 217-8 5-9 129-4 76-3 6-2 4th Case 1 821-8 178-2 5-8 114-3 58-1 5th Case | 800-2 808-1 199-8 191-9 6-0 7-1 131-3 125-5 62-5 59-3 6th Case 1 808-3 191-7 5-7 98-2 87-8 Healthy blood, 1 according to W90-0 210-0 3-0 127-0 80-0 Lecanu J ' Annal. de Chim. et de Phys., vol. 75, p. 225. BLOOD. 257 The decreasing ratio of the corpuscles, and the increasing ratio of fibrin is less striking in this disease than in pneumonia and rheumatism. Andral and Gavarret give the following ex- planation of the first case, in which the high number 148-8 is assigned to the blood-corpuscles. This individual exhibited symptoms of typhoid fever at the period at which he was re- ceived into the hospital. In the second analysis the number is less by 38-6 than before. The symptoms of typhoid fever had now disappeared, and made way for those of bronchitis: the increase of fibrin from 7-3 to 9-3 sufficiently indicates the progress of inflammation. In the fourth case the small quantity of solid constituents in the serum was coincident with a highly albuminous state of the urine; the patient, who was about 30 years of age, had for some time been in a weak and emaciated state. The urine in the fifth case, (a debilitated person 28 years of age, whose lower extremities were oedematous,) also contained albumen. Andral and Gavarret have likewise analysed the blood in chronic bronchitis. They state that, as the febrile symptoms disappear, and the disease assumes the chronic form, the blood ceases to exhibit a large excess of fibrin, and in fact does not differ in any respect from ordinaiy healthy blood. The same is the case if the clironic bronchitis is combined with pulmonary emphysema. The average of five analyses made on the blood of four per- sons suffering in this way, scarcely differs from ordinary blood. Water. Solid residue. Fibrin. Elood-corpuscles. ^°'''' P0'''^'0" of serum. Mean of five analyses . 792-7 207-3 3-0 121-0 830 Healthy blood (Lecauu) 790-0 210-0 3-0 127-0 80-0 In one of these cases a second venesection was ordered, in consequence of the severity of the dyspnoea. The blood exhi- bited a diminution of 11 in the coi-puscles, of -6 in the fibrin, and of 22 in the sohd constituents. [Scherer has published an analysis of the blood of a woman in the seventh month of pregnancy, who was suffering from bronchitis, and probably from tubercular phthisis. The serum had a specific gravity of 1022-69, and contained in 1000 parts : Water .... 911-516 Solid residue . . . 88-484 17 258 CIRCULATING FLUIDS The solid residue consisted of: Albumen .... 77"978 Extractive matters . . 0-977 Salts .... 9-529 The whole blood contained, in 1000 parts : Water .... 825-698 SoUd residue . . 174-302 Fibrin . . . 4-568 Albumen . . , 70-636 Blood-corpuscles . . 71-069 Extractive matters . 20-l78(?) Soluble salts . . 6-399 Earthy phosphates . 1-825 The serum presented a singular milky appearance, arising from the presence of numerous minute granules in suspension. No fat-vesicles could be recognized by the microscope. Becquerel and Rodier have analysed the blood in eight cases of acute bronchitis, foirr males and four females. The mean results are expressed in the following table : Density of defibrinated blood Density of serum Water Solid constituents Fibrin Fat . Albumen Blood-corpuscles Extractive matters and salts The salts consisted of : Chloride of sodium Other soluble salts Phosphates Iron . . . . Males. Females. 1056-7 1056-6 1027-1 1027-7 793-7 803-4 206-3 196-6 4-8 3-5 1-621 1-715 64-9 68-8 129-2 115-3 5-8 7-3 3-2 3-3 2-9 2-8 0-346 0-309 0-513 0-479.] |3. Pneumonia. The blood usually exhibits the characters of hyperinosis, more decidedly in pneumonia than in most other inflammatory diseases, it also retains its heat for a longer period.^ The clot is rather below the ordinary size, very consistent, and does not ' Lauer found that blood, which, as it flowed fi-om the vein, had a temperature of 97^-7, raised the thermometer to 83°-6 thirteen minutes after its removal from the body. i BLOOD. 259 break down for a considerable time. It admits of being sliced, and tlie sections retain their consistency for some time. Its sui'face is covered with the buffy coat, and is more or less cup- ped. The serum is of a pure yellow colour. The quantity of solid constituents is usually less than in healthy blood. The maximum of fibiin in my analyses was 9* 15, which is the largest quantity that I have ever discovered in inflamed blood. The minimum was 3"4, and the mean of four analyses was 6-0. Andral and Gavarret found the maximum of fibrin to be 10-5 ; the minimum 4; and the mean to fluctuate between 7 and 8. They never met with more than 10"5 of fibrin in the whole course of their analyses. The maximum of hgematoglobulin, occurring in my re- searches, was 78, and the minimum 36, which is very far below the amount in healthy blood. Andral and Gavarret diff'er from me considerably on this point, (see my remarks on our comparative methods of analysis, page 241.) They make the maximum of the blood-corpuscles 137, and the minimum 83*7. AVe find, however, in the course of 58 analyses, made by them on the blood of 21 persons labouring under pneumonia, that the amount of corpuscles just reached the normal propor- tion in 5 cases, in 6 cases exceeded it, and in the 47 remaining cases fell below it. The average of these cases was 113, which is 14 below the normal quantity in healthy blood, according to Lecanu's analysis. The maximum of fat, in my analysis, was 4'3, and the mi- nimum (in a man aged 60 years) was "7. The maximum of solid residue was 202; the minimum was 160. In 51 out of the 58 analyses, made by Andi'al and Gavarret, the solid constituents exceeded the ordinary normal proportion. In all these cases the quantity of the blood-corpuscles was very high : the fibrin, in two cases, reached 9*1 ; and in one case 9'0 : in the others it was low, or amounted to only the mean of the fibrin in pneumonia. The two highest amounts of solid residue found by Andral and Gavarret Avas 230, and 227 ; in these cases the maxima of corpuscles also occmTed. The smallest amount of solid residue was 166, which corresponded with the minimum of blood-cor- puscles. The mean quantity of solid residue, as deduced from 260 CIRCULATING FLUIDS : these 58 analyses, was 201, or 9 less than Leeanu's average for healthy blood. I have made four analyses of the blood in pneumonia : Analysis 19. Analj'sis 20. Analysis 21. Analysis 22. \\'ater 839-848 798-500 803-179 803-400 Solid residue 160-152 201-500 196-821 196-600 Fibrin 9152 6-020 5-632 3-443 Fat 2-265 4-100 4-336 0-697 Albumen 100-415 100-280 121-721 102-100 Globulin 34-730 74-880 52-071 74-948 Haematin 1-800 3-120 2-752 2-466 Extractive salts matters ^°n 8-003 10-500 10-309 11-258 100 parts of h The Lancet, Sept. 1840, p. 842. BLOOD, 319 Lecanui quotes an opinion of Delarive, that a change occurs in the colouring matter of the blood that escapes in haematuria, since sulphuric acid produces a brown-red instead of a black-red, and nitric and muriatic acids produce a white instead of a black- red precipitate : alcohol also produces a white deposit. These peculiarities in colour (especially the white precipitate) may pro- bably be explained by the precipitation of the albumen, while in consequence of the dilution of the blood the hsematoglobulin escapes precipitation. Purpura hemorrhagica. [The blood has been analysed in a case of this disease by Routier2. In 1000 parts he found: Water .... 795-244 Solid constituents . . 204-756 Fibrin .... 0-905 Blood-corpuscles . . 121-701 Residue of serum . . 83-405 From this anatysis it appears that the blood does not assume the form of spansemia. It is placed here in consequence of the analogy between purpui'a hemorrhagica and the preceding diseases,] Typhus petechialis putridus. Yellow fever. Plague. The blood in these diseases is described as watery, very poor in fibrin, and of a dark colour. If any clot be formed, it is diffluent, and very soft : the serum is frequently of a deep yellow or brown-red colour, partly from the colouring matter of the bile, and partly from dissolved hrematoglobulin. It possesses a very peculiar smell, which probably differs in each disease. It is by no means improbable that this smell may be produced by a volatile salt of ammonia. Schonlein has directed attention to the formation of a pecu- liar gas that escapes with the blood in the post-mortem exami- nation, on opening the large vascular trunks, and which is pro- bably developed in the blood during the last stage of the disease. Chomel also speaks of the development of a gas in the in- terior of the veins. ' Etudes chimiques, etc., p. 95. '■^ Gazette des Hopitaux, vol. 6, No. 90. 320 CIRCULATING FLUIDS : Ancelli remarks, tliat in the first stage of the endemic yellow fever of the West Indies the blood is of a brighter red, contains more salts, and is hotter than in a state of health. As the disease progresses, its characters become changed, and towards the termination of the malady it loses its saline and animal principles, and becomes black and thin ; in which state sangui- neous effusions occur from the different outlets and tissues. Balard and Rochet^ have made some observations on the properties of the blood in the plague. Balard is of opinion that the lymphatic system is first disor- dered, and that inflammation, degeneration, and suppuration of the lymphatic ganglia and vessels follow. It is not until sup- puration in these structures has fairly set in that the venous system begins to suffer, and a change in the composition of the blood to ensue. The blood, when the disease is fully established, exhibits in- variably the same properties, whether it is obtained by bleeding, or taken from the vessels after death. The arterial and venous blood have both the same dark colour; the blood generally appears in a peculiar state of solution, and oily drops are fre- quently seen on its surface. It frequently has a peculiar smell, but never the buffy coat. In three patients, aged 19, 23, and 27 years respectively, and in whom the blood was drawn between the third and fifth days, it was of a dark-brown colour, and in the course of two hours a good clot was formed. This, however, is frequently not the case, especially when the oily globules appear. The serum was reddish, and developed a gas which soon browned sugar of lead test-paper, and which therefore contained sulphuretted hydrogen. The clot constituted about 40^, and contained 33-5 of water, •6 of fibrin, 3-8 of cruor, -25 osmazome, "9 of chlorides of sodium and potassium, and -2 of carbonate of soda and fat. Lacheze,3 who observed the plague in Egypt, states that the blood never coagulates, that it is greasy, and of a black colour. ' Course of Lectures on the Physiology and Pathology of the Blood. The Lancet, 1840, p. 837. 2 Casper's Wochenschrift, 1838, No. 12. ^ Magendie, Lemons sur le Sang. Bruxelles, 1839, p. 200. BLOOD. 321 THE FOURTH FORM OF DISEASED BLOOD : HETEROCHYMEUSIS.' I arrange under this form all those states of the blood in which a substance is present that does not exist in the normal fluid : when, for instance, the blood contains urea (in appreci- able quantity), sugar, colouring matter of the bile, fat, or pus. The cii'cumstances that lead to the establishment of this diseased condition of the blood are far less natui'al than those which are connected with the j)roduction of the thi'ee former classes. The arrangement is artificial, and merely adopted for convenience, since this class of diseases has simply this property in common, that the composition of the blood is here qualitatively changed, whilst in the three former it was only altered quantitatively. The putrid form of typhus, the yellow fever, and the plague, certainly might have been placed in this class, since colouring matter of the bile, and a salt of ammonia, are often found in the serum. I have, however, thought it best to place these dis- eases in the third class, because, in the first place, the presence of the abnormal constituents is not constant ; and because, se- condly, in consequence of the deficiency in the solid constitu- ents of the blood in these disorders, they naturally occur under the class spansemia. I. BLOOD CONTAINING UREA: UREMIA, a. Morbus Brightii. Andral and Gavarret describe the blood in this disease as characterized by a deficiency of albumen in the serum. It is evident, however, both from my own and fromChristison's researches, that the decrease of the solid constituents of the serum is not always the leading character in this disease. I have thought it right, therefore, to arrange this disease, on ac- count of the nearly constant presence of urea in the blood, under the form heterochymeusis. Christison,^ who has attentively studied the blood in this dis- ease, describes it in the following manner : The blood in the first stage of the disease coagulates with a thick, firm, and cupped buffy coat. The serum is usually rather turbid, and when shaken ' From irtpoQ and xujxivoiQ. * Oa the Granular Degeneration of the Kidnevs, etc., hvR. Christison. Edin. 1839. 21 322 CIRCULATING FLUIDS: with ether yields a small quantity of solid fat. The decrease in the density of the serum at this stage is very remarkable. While in healthy blood it is estimated at 1029 — 1031, it now sinks to 1020, or even 1019 ; and in connexion with this circumstance we find a large quantity of albumen in the urine. Another very remarkable peculiarity is the presence of a cer- tain quantity of urea in the serum. The following changes occur in the progress of the disease : (1.) There is an excess of serum, the clot often constituting not more than one fomth of the blood. (2.) The density of the serum returns to its normal state, or even exceeds it ; some- times, however, it remains low, even in the advanced stages. (3.) The urea disappears as the disease advances, but usually reappears, towards the termination of the case, in even a larger amount than pre\dously. (4.) The fibrin, which is increased in the first stage, returns to its normal amount as the disease advances, and only becomes considerable again during inflam- matory complication. (5.) The most remarkable character of the blood in the advanced stage is the great decrease of blood- corpuscles, which frequently amount to only one third of the normal proportion. I have analysed the blood in four cases of Bright's disease, and obtained the following; results : Analysis 36. Analysis 37. Analysis 38. Analysis 39. Water . . 830-590 826-891 823-461 839-700 Solid constituents . 169-420 173-109 176-539 160-300 Fil)rin 7-046 3-060 5-000 3-500 Fat 2-403 1-860 2-520 2-680 Albumen 103-694 109-432 97-010 63-400 Globulin 40-151 41-300 54-090 71-300 Ilseniatin 3-808 4-377 5-100 4-910 Extractive matters and salts 12-348 13-280 12-819 11-380 The blood in analysis 36 was taken from a man aged 40, who had been treated for some time in our hospital for this disease : traces of urea were detected in the extractive matters, by the method given in page 183. — The blood in analysis 37 was taken from a man aged 20, whose feet and arms were so oedematous as to render venesection a matter of some difficulty. Consider- able quantities of urea were found in the blood. — The blood in analysis 38 was taken from a man aged 30, in whom the dis- ease was not so advanced as in the former cases. A consider- BLOOD. 323 able quantity of urea was found in the serum, which exhibited a remarkable milk-white turbidity, not caused by fat in a state of suspension, but (as sho-mi by the microscope) produced by numerous minute solid granules, which, by diluting the serum, and then allowing it to rest, were collected, washed, and analysed. They were not soluble in alcohol or in ether, but dissolved after a continuous digestion in dilute acetic acid, from which they were precipitated by ferrocyanide of potassium. Hence I concluded that they were fibrin. The blood in analysis 39 was taken from a man 36 years of age, at the commencement of the disease. Hsematuria had oc- cmred a few days pre^^ous to the venesection. The quantity of urea in this blood was very considerable. — The urine was albu- minous in all these cases, especially in the last two. It is worthy of remai'k that I have found the ha^matoglobulin more abundant in hsematin in these than in ordinary cases. It varied from 8^ to 9"5§. Chi'istison gives the following results of analyses of blood in Bright's disease : Water. Solid constituents. Fibrin. Blood-corpuscles. Residue of serum 1 863-8 136-2 2-8 57-4 76-0 2 844-1 155-9 4-4 57-7 93-8 3 808-3 191-7 3-0 133-9 54-8 4 831-0 169-0 2-8 111-1 551 5 836-3 163-7 2-7 104-6 56-4 6 825-2 174-8 4-3 95-5 750 7 859-2 140-8 8-2 75-5 57-2 8 885-3 114-7 6-2 56-4 521 9 862-8 137-2 3-2 721 61-9 10 855-5 144-5 4-5 42-7 97-3 11 862-6 137-4 8-5 72-8 561 12 887-0 1130 5-6 49-1 58-3 13 841-6 158-4 3-4 91-6 63-4 Christison^s average composition of healthy blood being : 775-7 224-3 38 137-1 83-4 The blood in the 3d analysis was taken from a robust man, aged 55 years, in the first stage of granular degeneration, and suflfering from anasarca. The urine was very albuminous, but not bloody : the serum was milky, and abounded in urea. The blood in the 5th analysis was taken from a man aged 48, suffering from anasarca and continued fever. The kidneys were in the first stage of granular degeneration; the urine contained 324 CIRCULATING FLUIDS: a considerable quantity of albumen. — In the 6tli case, the dis- ease bad reached the middle stage : the patient was at the same time suffering from anasarca and chronic catarrh: the blood contained m^ea. — In the 7th case, the disease was in the first stage; the patient (a man aged 42) was also suffering from peripneumonia and anasarca: the blood contained lu-ea, and the urine was albuminous. 8th analysis. Blood of a youth aged 16 years, suffering from dropsy ; kidneys in the middle stage of granular degene- ration. The serum was peculiarly rich in solid constituents, and contained a considerable quantity of urea. 9th analysis. Blood of a man aged 23. The granular degene- ration was more advanced, the blood contained urea. 10th analysis. Blood of a man aged 23, after having re- covered from scarlatina. The disease in the kidneys was in an advanced stage : the blood was remarkable for the small quantity of corpuscles. 11th analysis. Blood of a woman aged 25 years, suffering from anasarca, catarrh, and chronic rheumatism. The dege- neration of the kidneys was in a very advanced stage. The blood contained urea, and the urine was albuminous. 12th analysis. Blood of a man aged 32, suffering from pleuritis and anasarca; kidneys in an advanced stage of the dis- ease. Blood remarkable for the small quantity of corpuscles, and for the large amount of urea. 13th analysis. Blood of a woman aged 56, with anasarca and ascites ; the disease of the kidneys was in a very advanced stage. These observations entirely coincide with my own, as far as regards the decreased quantity of solid constituents, the small amount of blood-corpuscles, as the disease advances, and the presence of urea in the blood. Andral and Gavarret have analysed the blood of three per- sons with Bright's disease. The following are their results: Venesection. Water. Solid constituents. Fibrin. Blood-corpuscles. Residue of serum. 1st Case 1 801-0 199-0 1-6 127-6 69-1 2d „ 1 867-0 133-0 2-3 61-6 68-4 fl 849-0 151-0 3-2 82-4 64-8 3d „ -^ 2 836-0 164-0 3-0 88-2 72-7 U 845-9 154-1 4-2 71-0 78-9 BLOOD. .325 The second venesection in tlie 3d case was ordered at a time when the urine was less albuminous than it had been : the third was prescribed after a considerable interval, and when the urine contained no albumen. j3. Cholera. The researches of trust-worthy observers have shown that the blood in cholera exhibits the following peculiarities. The quantity of water is decreased, and consequently there is an increase in the amount of solid constituents arising, in all pro- bability, from the watery alvine evacuations ; the amount of fibrin, as well as the alkaline reaction, is diminished, and urea is found in the serum. The search after this substance has not always been successful, but its presence has been clearly shown by Rainy, 1 O^Shauglmessy,^ ]Marchand,3 and myself. The following are the leading physical characters of the blood in this disease. It appears to be thicker than usual, and either forms a soft, friable clot, or else coagulates very imperfectly. Wittstock has made a careful analysis of the blood during cholera. In its external characters it resembled healthy blood : the clot was of a scarlet red colour on the surface, but darker than usual in the interior. His analysis gave the following results: serum 36-52, clot G3-5|^. The specific gravity of the serum was 1-0385, and 100 parts left 13-75 of solid residue. The clot, when treated with ab- solute alcohol, left a residue of 2>\l; the alcohol took up solid crystalline, and thin fluid fat, chlorides of sodium and potassium, lactates of soda and ammonia, extract of flesh, and traces of phosphate of lime. By washing the clot, 6^ of fibrin were ob- tained. Hence, if we consider the fluid of the clot to be serum, we have the composition of this blood expressed as follows : Water .... 740-00 Solid residue . . . 260-00 Fibrin . . . . 11-00 Albumen .... 110-42 Blood-corpuscles . . 124-46 Extractive matters and salts 14-10 ' London Medical Gazette, Jan. 1838. * Ancell's Lectui-es on the Blood. The Lancet, 1840, p. 840. ^ Poggendorf s Annalen, vol. 49, p. 328. 326 CIRCULATING FLUIDS : The blood-corpuscles, therefore, fall below Lecanu's average, while the albumen aud solid constituents, generally, are consi- derably increased. Lecanui has made several experiments upon the quantity of solid constituents in the blood in cholera, and has arrived at the following results : SoUd constituents . . 340 251 520 330 Water .... 660 749 480 670 0'Shaughnessy2 has analysed the serum of the blood in this disease, and has detected a considerable quantity of urea in it. 1000 parts were composed of. Water 854-0 Albumen 133-0 Urea 14 Crj'stalline and fluid fat .... 1-4 Chlorides of sodium and potassium . . . 4-0 Sulphates and muriates 1'6 Extractive matter and albuminate of soda • 4-8 I analysed the blood of a woman labouring under a severe attack of sporadic cholera. 1000 parts of blood contained : Analysis 4o. Water .... 750-530 Solid constituents . . 249-470 Fibrin .... 2-470 Fat .... 5-434 Albumen . . . 114-114 HsematoglobuUn . . 108-529 Extractive matters and salts 10*631 The salts amounted to only 5-41, the average quantity being from 7 to 8 in 1000 parts of blood. We see that the water is decidedly diminished, but the ratio of the blood-corpuscles to the albumen is not such as was formerly supposed.^ In con- sequence of the suppression of the urinary and biliary secre- tions, the blood contained a quantity of urea and of the con- stituents of the bile, (bilin and biliverdin.) [Heller examined the blood taken after death from the ca- rotids of a man who died of sporadic cholera. ' Etudes chimiques, etc., p. 106. * Ancell's Lectures on the Blood. Lancet, 1840, p. 840. 3 It was conceived that the thick and often imperfectly coagulated blood must be vei-y rich in corpuscles, in consequence of the amount of serum thrown off by the intestinal canal. BLOOD. 327 It was of a very dark colour and of a tolerably tliick con- sistency. Under the microscope the blood-corpuscles appeared hacked at the edgeSj as if the capsules were partially destroyed, and many fat-vesicles were seen. The blood was very rich in albumen, in fat, and in urea. The fixed salts, especially the chlorides, were increased,^ and the fibrin appeared to be beneath the normal standard. There was no trace of biliphaein.] II. SUGAR IN THE BLOOD: MELIT^MIA. The blood in diabetes has been found by several observers, and in one instance by myself, to contain a larger proportion of solid constituents than healthy blood : others, as Lecanu and Henry, state that the amount is smaller. According to the latter, the quantity of blood-corpuscles is diminished, while others assert that they are increased. The fibrin remains at about the normal quantity. Hollo was, I believe, the first who proved the presence of sugar in the blood during diabetes. Gueudevine,2 Vauquelin, Segalas,^ WoUaston, Henry and Soubeiran, could not detect it. Bouchardat,* however, directs attention to the important consideration that the presence of sugar in the blood can only be incontestably proved when ve- nesection has been performed two or three hours after dinner, and that if blood is drawn in the morning, no traces of it can be found : I have corroborated this observation. I have analysed the blood in three cases of diabetes. The sugar was sought for in the manner described in page 185. Analysis 41. Analysis 42. Analysis 43. Water 794-663 789-480 802-000 Solid constituents 205-337 210-510 198-000 Fibrin 2-432 2-370 2-030 Fat . 2-010 3-640 2-250 Albumen 114-570 86-000 97-450 Globulin 66-300 98-500 74-350 Hccmatin 5-425 5-100 3-700 Sugar 2-500 a trace a trace Extractive matters and salts 9-070 14-900 12-680 ' In consequence of the torpidity of the urinary secretion. ^ Annal. de Chimie, vol. 44, p. 45. ^ Journal de Chimie Medicale, vol. 1, p. 1. ^ Revue Medic. 1839, p. 321. 328 CIRCULATING FLUIDS: The blood in analysis 41 was obtained from a man aged 50 years, who had taken a full meal of animal food two hours pre- vious to being bled. The 2-5 parts of sugar were not perfectly pure; they contained extractive matter, and some salts. The blood in analysis 42 was taken before dinner from a girl aged 20 years. The presence of sugar was only just per- ceptible by the taste, by the sulphiiric acid test, and by the odour evolved on burning it. The disease in this case was far advanced, and it is worthy of remark that, six or eight days pre- vious to dissolution, the diabetes sapidus became converted into diabetes insipidus. This patient made an extremely large quantity of water, which was not very abundant in sugar; while the man, aged 50, passed only two or three quarts of urine daily, containing a large proportion of sugar. The blood in analysis 43 was taken before dinner from a man aged 30 years, who passed a very large quantity of water, which, however, did not contain much sugar. I give, in the following table, the analyses of other observers:^ Boueliardat. Henry and Soubeiran. Lecanu. Water . . . 80876 816-50 848-35 Solid constituents . 191-24 183-50 151-65 Fibrin . . . 1-95 2-43 Albumen . . . 62-54 55-48 58-47 Blood-corpuscles . 118-25 120-37 85-18 Salts . . . 8-52 5-57 8-00 I further add the following analysis of the serum in diabetes, made by Eees.2 Water 908-50 Albumen, with a trace of phosphate of lime and peroxide of iron 80-35 Fat 0-95 Diabetic sugar 1-80 Alcohol-extract and urea . . . . . . 2-20 Albuminate of soda, alkaline chlorides and carbonates, with a trace of sulphates and phosphates .... 0-80 [Some very important additions to our knowledge of the pathology of this obscure disease will be found in Dr. Percy's ' Observations and Experiments concerning diabetes mellitus.' Med. Gaz. vol. ii, 1843.] • In addition to those quoted in the text, there is an analysis of diabetic blood by Midler in the Archiv d. Pharm., vol. 18, p. 55. Its extreme peculiarity renders its correctness doubtful. * Ancell's Lectures on the Blood. The Lancet, 1840, p. 889. BLOOD. 329 III. BILE-PIGMENT IN THE BLOOD : CHOL.EMIA. Very contradictoiy statements exist regarding the composi- tion of the blood in icterus. Orfila^ found bile, or at least, biliar}^ resin, in the blood of three persons suffering from icterus ; and Collard dc Martigny'^ and Clarion^ obtained similar results. Lassaigne* and Thenard, on the contraiy, declare that they could never detect any con- stituent of the bile in such cases. Chevi'eul found, in the blood of children with icterus, the colouring matter of the bile, but not picromel j and Boudet and Lecanu have likewise found the bile-pigment present in these cases. I was fortunate enough to obtain a specimen of the blood of a woman in our hospital who was jaundiced to a degree not often witnessed. The skin over the whole body was of a yel- lowish brown colour, the urine was of a deep, dark brown tint, and deposited a considerable quantity of brown and yellow sedi- ment. The blood was drawn from the arm in my presence, and was immediately whipt. It hardly differed in appearance from normal blood, but contained very little fibrin, and the corpus- cles speedily sunk. The serum was of an almost blood-red colour, but, when only a thin stratum was viewed, it appeared of a bright amber tint. Its taste was hardly at aU bitter ; when treated with nitric acid, a whitish yellow coagulum was first formed, (consisting of albumen,) which rapidly assumed a deep grass-green colour, then, after a short interval, changed into a blue, and afterwards into a pale red ; and from that to a yellow. I precipitated the protein- compounds, by means of alcohol, from a large quantity of serum, evaporated the fluid, again treated the residue with alcohol, evaporated, and then dissolved the residue in water. This aqueous solution must have con- tained bilin or bilifellinic acid (if they had been present), besides the alcohol-extract of the blood and certain salts, but it neither tasted bitter, nor, Avhen digested with sulphuric acid, did it yield a resinous substance (a compound of fellinic and cholinic acids ' Elements de Chim., vol. 2, p. 313. 2 Joui-n de Chim. Med., vol. 3, p. 423. ' Theses d'Ecole de Medecine, 1811. * Journ. de Chim. Med., vol. 1, p. 266. ' Trait c de Chim., vol. 5, p. 111. 330 CIRCULATING FLUIDS and dyslysin) ; neither did it contain bilin nor any of the pro- ducts of its metamorphosis. On the other hand, I found, in the urine of this person, which was brown, very acid, and contained a large quantity of uric acid, a very appreciable quantity of biliary resin. We can only account for the occurrence of this product of the metamorphosis of bilin in the urine, by recollecting the facility and rapidity with which noxious matters are eliminated from the blood. My analysis of the blood in icterus gave the following results : Analysis 44. Water 770-000 Solid residue 230000 Fibrin 1-500 Fat 2-640 Albumen 126500 Globulin 72-600 Haematin 4-840 Haemaphaein, with biliphaein . , . 2-640 Extractive matters and salts, with biliphaein . 16-500 The peculiarities of this blood are, its large amount of solid constituents, due to an increase, not of the corpuscles, but of the albumen, the diminished quantity of fibrin, and the excess of colouring and extractive matters and salts. In other analyses of the blood I have frequently found it impossible to separate the hsemaphsein from the hsematin, in consequence of the small amount of the whole colouring matter ; in this instance, how- ever, I was able to effect their separation, and it appears that the amount of the hsemaphsein is about one half of that of the hasmatin, a proportion which is probably larger than occurs in healthy blood. The fat was not particularly increased. The researches of Denis and Lecanu give, to a certain degree, similar results : they show a decrease of the blood-corpuscles, but not an increase of the solid constituents. Lecanu. Denis. 1. 2. Water .... 828-660 830-0 815-00 Solid constituents 171-340 170-0 185-00 Fibrin .... 9-50 Fat 600 Albumen .... 76-800 65-0 5300 Blood-corpuscles 79-620 97-0 93-95 Salts .... 8-00 Yellow and blue pigment 14-55 Salts, extractive matters, and fat IJ-'JOO 8-0 BLOOD. 331 The large amount of fibrin and of fat is remarkable in Denis's analysis : the 14*5 parts of colouring matters were probably combined with extractive matter. Tiedemann and Gmelin observed that the clot of icteric blood was of the ordinary colour. The clear yellow serum contained biliphsein, and gave, when treated with a small quantity of hydrochloric acid, a hyacinth-red colour, which, in the course of the night, became green ; if an excess of acid was used, a hyacinth-red colour was at once produced, which, in the course of the night, turned to a blue. When treated with a quantity of nitric acid not sufficient to precipitate the albumen, it became of a greenish yellow colom* ; when treated with an excess of the acid, it gave a green precipitate, which afterwards became blue, and subsequently violet, red, and yellow. [Becquerel and Rodier observe that, in icterus, there may be a continued secretion and flow of bile, or there may be perfect retention arising from biliary calculi, &c. In the first case, no peculiar modification is observable in the blood, and it is, therefore, unnecessary to quote their analyses ; in the second case, there is an accumulation of cholesterin and of the other fatty matters in the blood. The following analysis was made of the blood of a young man, aged 23 years, in whom icterus was developed as a conse- quence of indigestion. There was constipation, and no appear- ance of bile in the faeces. The blood contained, in 1000 parts : Water .... 740-509 Solid constituents 259-491 Fibrin 1-900 Fat ... 3-646 Albumen 66-300 Blood-corpuscles 164-300 Extractive matters and salt' i 23-345 The fatty matters amount to more than double the normal quantity, and consisted of : SeroUn .... 0-070 Phosphorized fat . . 0-810 Cholesterin . . . 0-627 Saponified fat . . . 2-139 The fatty acids that enter into the composition of the sapo- nified fat occur in the bile, combined with soda. The salts were normal. 332 CIRCULATING FLUIDS : In another case of a similar nature, the fat amounted to 4" 176, consisting of; Serolin . . . , 0-128 Phosphorized fat . . 1*159 Cholesterin . . . 0-556 Saponified fat . . . 2-333 In adddition to the large amount of fat in the blood in these cases, Becquerel and Rodier observed that the serum was always tinged with bile-pigment.] IV. FAT IN THE BLOOD : PIARH^MIA. It is well known that free fat in the form of globules is not ordinarily seen in healthy human blood. The greater part exists in a saponified state, with the exception of cholesterin and serolin, which do not saponify with potash. As, however, the chyle contains a large quantity of free fat soon after the act of digestion, we must conclude that during the process of me- tamorphosis of the blood the greater part becomes converted into fatty acids. In certain pathological states of those organs which play an active part in the metamorphosis of the blood, and whose cells contain a considerable quantit}^ of fat, as the liver and kidneys, and during inflammatory affections of the peritoneum and of the lungs, so large a quantity of both free and combined fat is sometimes found in the blood, that the serum appears turbid, opaque, and even milky. Marcet found the serum milky in diabetes. Trail in hepatitis, Zanarelli in pneumonia, Christison in droj)sy, icterus, and ne- phritis ; moreover, in cholera the blood has been found to be very abundant in fat. It is hardly necessary to observe that if in such cases the serum appear turbid, whey-like, or milky, fat-globules will be perceptible under the microscope. Christison and Lecanu^ have found that this, like most of the animal fats, consists of olein, margarin, and stearin : there is little doubt but that fatty acids are also present; in fact, Lassaigne detected a fat of this nature in the blood, similar to the fatty mat- ter of the brain. Zanarelli^ found the blood of a man with pneumonia similar ' Etudes chimiques, p. 116. ' Journal de Chimie Medic, vol. 2, p. 551. BLOOD. 333 to milk : it separated into a thicker and a thinner portion. Blood taken some days afterwards separated into a red clot and into a milky serum. Zanarelli is of opinion that this milky blood is chyle, which has not been converted into proper blood, in con- sequence of the affection of the lungs. Bertazzi analysed it, and his results ai'e given below. Bertazzi' s Analysis of Milky Blood. Water 905-0 Solid constituents ...... 95*0 Crystalline fat ...... 4"0 Non-crystalline fat 6*0 Extractive matter, lactates, and chlorides . . 5"0 Carbonates, phosphates, and sulphates . . 4*0 Dr. Sioni observed an instance of milky blood in a case of mammary abscess. It contained no fibrin, and when allowed to stand a small quantity of colouring matter was deposited. The fluid was analysed by Lecanu, and the following are the results he obtained : Lecanu' s Analysis of Milky Blood. Water 794-0 Solid constituents 206*0 Albumen 64-0 Fat ; cholesterin, margarin, stearin, and fatty acids 1 1 7*0 Salts and extractive matter . . . 25-0 Haematoglobulin ..... a trace. In a case of milky serum, which occurred during hepatitis. Trail found : Water .... 789 Albumen . . . . 157 Oily fat ... . 45 Chlorides and lactates . . 9 V. PUS IN THE BLOOD : PYOHiEMIA. According to Gulliver,^ pus is found, and probably is also formed, in the blood in all diseases in which there is suppura- tion, or even inflammatory swelling, accompanied with hectic fever. According to Blandin, blood of this nature, in issuing from the vein, does not diff'er much in appearance from ordinary blood ; it is frequently, however, rather darker and more fluid. When the blood is inflamed and purulent, a muddy or greenish ' Lancette fran?. 1835, No. 49. « Lond. and Edin. Phil. Mag. 1838. 334 CIRCULATING FLUIDS: yellow inflammatory coat is formed, in which, according toPiorry, gray granulations of a pnriform appearance occur. Ammonia has been recommended by Donne as a test for the presence of pus in the blood. Blood treated with ammonia dis- solves into a clear fluid, while pus similarly treated forms a stiff" jelly. If, therefore, blood contains pus, it will become more or less gelatinous upon the addition of ammonia, and if only a very small quantity of pus is present, then we shall only find stripes of this stringy substance deposited at the bottom of the vessel. I have obtained favorable results from this method when the quantity of pus has not been very minute ; I will not, however, venture to assert that certain results can be obtained by this method when the amount of pus is extremely small. Gulliver,! Gluge,2 and many others have availed themselves of the microscope for the detection of pus in the blood, and I am inclined to believe that this method gives the most certain results. The blood contains, in addition to its own corpuscles, the so-termed chyle-corpuscles, which ai'e one half, or even quite, as large again as the blood-corpuscles. They do not possess the yellow colom' of the latter ; they are gray, only slightly gra- nular, and possess a sharp, dark, circumscribed edge ; their rolling motion, on inclining the stage of the microscope, shows that they are perfectly spherical, and they do not, like the blood-corpuscles, dissolve in water. If, however, the chyle-cor- puscles remain in contact with water for some time (from half an hour to an hour), they undergo a change ; they increase a little in size, become clearer, their edge appears less sharp, theii' shape is no longer spherical, but oblong or iiTcgular, and they become more distinctly granular, or else dark points become apparent in the interior, as indications of nuclei. In this con- dition the chyle-corpuscles may be easily mistaken for pus-cor- puscles ; the latter are, however, usually rather larger than the tumefied chyle-corpuscles, and they are paler, their edge is granu- lar, or tuberculated, and often very uneven, their shape is round, or oblong, occasionally irregular, and they appear slightly gra- nular in the interior, indicating from three to five nuclei. In very many cases we see two, three, five, or even more pus-cor- ' Op. cit. ^ Fragmeiite zur Pathologic des Blutes. Anatomisch-Mikroskopische Untersuch- ungen. Heft 1. 1839. BLOOD. 335 puscles lying closely attached to each other, while the chyle- corpuscles almost always swim about separately. 3iy this means I have recognized pus in the blood, both when it has been arti- ficially placed there, and on analysing the blood which I took from the inflamed vein of a person who had died from plilebitis. In one instance, in which I found a considerable quantity of pus in the blood, taken from the inflamed vein in a case of traumatic phlebitis, I could detect no traces of pus in the blood taken from the vena cava and from the heart. This is all that I can state from my own experience regard- ing the detection of pus in the blood. VI. ANIMALS IN THE BLOOD. Early authors speak of li\dng animals in the blood. Dr. Chiaje,^ of Naples, has recently stated that he found the polystoma san- guiculum in the expectorated blood of two phthisical patients who were attacked with haemoptysis. Some of these small flat worms, which are similar to leeches, were floating about in the serum, others attached themselves to the sides of the vessel. Chiaje characterizes the polystoma in the following terms : " Cor- pus teretiusculum, sen depressum, pori sex antici ventrales, et posticus solitarius ; habitat in venoso systemate hominis, et prae- sertim in ejusdem pulmonali parenchymate." [Dr. Goodfellowhas latelyrecorded a case in which an immense number of animalculse were found in the blood of a fever-patient. They varied in length from 1 -5000th to 1 -3000th of an inch, and in diameter, which was the same throughout, from 1 -40,000th to 1 -20,000th of an inch. A singular case was observed by Mr. Bushman, in which worms of about half an inch in length were found in the blood of a boy labouring under influenza. — Ancell^s Lectures on the Blood. * Lancet,^ 1840, p. 778.] SUPPLEMENT. The following analyses of the blood of a pregnant woman (in her fifth month), and of menstrual blood, could not be naturally inserted among either of our four forms of diseased blood, and will find a proper place in a supplement. ' Omodei, Annali universal., Oct. 1837. 336 CIRCULATING FLUIDS The blood of the pregnant woman formed a sUght bufFy coat, but otherwise differed in no respect physically from normal blood. It was composed of: Analysis 45. Water .... 806-898 Solid constituents 193102 Fibrin .... 2-102 Fat .... 3-040 Albumen .... 72-200 Hsematoglobiilin 96-900 Extractive matters and salts 7-980 The chief point of difference between this and normal blood is that, in this case, the amount of solid constituents is some- what below the standard. The proportion of the hsematoglo- bulin to the albumen is normal; the quantity of fat is rather increased. [Becquerel and Rodier analysed the blood of nine pregnant women, viz. one at the fourth month, five at the fifth month, one at five months and a half, one at six months, and one at seven months. The maxima, minima, and mean results are given in the fol- loAving table : Mean. Max. Mill. Density of detibrinated blood 1051-5 10551 1046-2 Density of serum 1025-5 1026-8 1023-6 Water .... 801-6 Fibrin .... 3-5 4-0 2-5 Albumen .... 66-1 68-8 62-4 Blood-corpuscles 111-8 127-1 87-7 Extractive matters and salts 6-6 8-7 4-7 Fat .... 1-922 2-519 1-158 Consisting of — Serolin . variable 0-108 0-018 Phosphorized fa t 0-646 0-863 0-381 Cholesterin 0061 0-225 0-030 Saponified fat 1-195 1-323 0-737 The salts in 1000 parts < df blood consisted of : Chloride of sodium 3-2 3-9 2-3 Other soluble salts 2-4 2-8 1-8 Phosphates 0-425 0-690 0-282 Iron .... 0-449 0-490 0-370 From these analyses they conclude that pregnancy exercises a marked influence on the composition of the blood. The density both of the defibrinated blood and of the serum is BLOOD. 337 diminished, the water, the fibrin, and the phosphorizcd fat^ arc increased, while tlie corpuscles and the albumen are diminished.] The menstrual blood was obtained at a period at which it contained no epithelium scales. It did not coagulate ; it con- tained some vaginal mucus, but it was not putrid nor of an unpleasant smell. It was composed of: Analysis 46. 785-000 215-000 2-580 76-540 120-400 8-600 The most striking peculiarities of this blood are, the total absence of fibrin, and the increase of the solid constituents caused by the excess of the blood-corpuscles. The haimato- globulin was found to be very rich in hsematin, combined, un- doubtedly, with a considerable amount of hsemaphsein; the colouring matter amounted to 8-3^ of the hsematoglobulin. Water Solid constituents Fat . Albumen Haematoglobulin Extractive matters and salts [In an analysis made by Denis, and quoted by Raciborski in his Essay on Menstruation, (in I'Experience, No. 333,) the menstrual fluid was found to consist of: Water 825-0 Solid constituents .... 175*0 Fibrin 0-5 Phosphorized fat . . . . 3-9 Albumen ..... 48-3 Blood-corpuscles .... 63-4 Mucus 45-3 Osmazome and cruorin ... I'l Soluble salts 9-5 Earthy phosphates and carbonates . 2-5 Peroxide of iron .... 0-5 Rindskopf analysed the menstrual discharge of a vigorous and healthy girl. It was extremely acid, and contained : 1st Analysis, j 2d Analysis. Water .... 820-830 Water .... 822-892 Solid residue . . . 179-170 I Albumen and haematoglobulin 156-457 Salts .... 10-150 Extractive matters and salts 20-651 The phosphorized fat is alwavs abundant in impoverished blood. 22 338 CIRCULATING FLUIDS : Vogel analysed the menstrual discliarge in a case of pro- lapsed uterus. It was of an intensely red colour, thick, and viscid ; it did not coagulate, but, after standing for some time, a colourless serum separated. The fluid obtained at the com- mencement of the flux yielded 83-9 parts of water and 16-1 of solid materials, and that obtained near the termination yielded 83-7 of water and 16-3 of solid materials. The serum contained 93-53 parts of water and 6-47 of solids, of which 0-64 were fixed salts. There can be little doubt that there is fibrin in the menstnial secretion ; its determination is, however, usually ren- dered impossible by the presence of a large amount of mucus, which seems to deprive the blood of its power of coagulating. Lochia! discharge. Scherer has carefully investigated this subject. The following is a summary of his results. During the first day the discharge was of a brownish red colour, \dscid, formed no coagulum, but, when collected in a vessel, threw down a slimy deposit, consisting of normal blood- corpuscles, with which a few partially- dissolved and broken-up corpuscles, together with mucus-corpuscles and epithelium scales were interspersed. The supernatant serum was clear and yel- low, and the microscope revealed in it a large number of fat- vesicles. It was devoid of odour, perfectly neutral, and contained in 1000 parts : Water 740 Solid constituents . . 260 On the second day there were still blood-corpuscles, but they were fewer and less perfect, most of them being irregular and indentated at the edges ; there were mucus-corpuscles and epi- thelium scales, but in less number than on the preceding day. The fluid still deposited a viscid sediment, but the serum was more highly coloured than on the previous day. The reaction was neutral ; there was a faint odour. 1000 parts consisted of: Water .... 812-2 Solid constituents . . 187-8 The residue, on incineration, yielded 9*35 of alkaline ferru- ginous ash. On the third day the secretion resembled arterial blood. The blood-corpuscles were, for the most part, perfect, and normal mucus-corpuscles were observed. BLOOD. 339 In 1000 parts there were : Water 760 Solid constituents . . 240 The ash amounted to 12*2. There, was an appreciable quan- tity of fibrin in this day^s secretion, arising possibly from a slight hsemorrhagic effusion. On the fourth day the secretion was of a dirty brown colour, the corpuscles were more or less injured, and there was a dis- tinct odour of ammonia. There were numerous mucus-cor- puscles, but no epithelium. 1000 parts yielded 191 of solid residue, and 9-5 of alkaline salts. On the fifth day the discharge was of a greenish yeUow colour ; it contained very few blood-corpuscles, most of which were more or less injured, but numerous mucus-corpuscles arranged in groups of 5 — 10 together. The reaction of the fluid was alka- line, there was a strong odour of ammonia, and 1000 parts yielded 93*5 of solid residue. On the sixth day the fluid was of a brown colour, smelled like putrid cheese, and developed ammonia freely. 1000 parts gave 76 of solid residue. For other analyses and further infor- mation on this subject the reader is referred to ' Scherer's ChemischeundMikroskopischeUntersuchungungzur Pathologic.' Heidelberg, 1843.J Blood of animals. In addition to the 12 analyses of horse's blood which have already appeared, I may communicate the three following : Analysis 47. Analysis 48. Analysis 49 Water • . 800-562 818-900 808-809 Solid constituents 199-437 182-100 191191 Fibrin 4-747 5-100 9011 Fat . 5-149 2-214 4-820 Albumen 62-276 62-140 103-740 HiEmatoglobulin 100-291 96-100 58-960 Extractive matters and salts 12-454 12-310 14-650 The blood in aU these analyses was taken from horses suf- fering from malleus humidus. Analyses 48 and 49 refer to the same horse, but in the latter case the animal was kept for four days without food, being merely allowed water during that period. Taking into consideration the deprivation of nutriment, 340 CIRCULATING FLUIDS: we cannot help feeling surprised at the large amount of solid constituents that occur in this analysis ; it can only he explained by supposing that a larger amount of fluid was removed from the blood by secretion and excretion than was supplied to it by the drink. Another pecuharity is the increase of fibrin and of fat, and the diminution of blood-corpuscles; this change may, how- ever, be readily explained, for as long as the organs of respiration, secretion, and excretion, continue to discharge their functions, the blood must obviously be changed by them, and this change will especially affect the corpuscles. The horse passed little urine during this time, but this little was tolerably saturated. It was by no means strong at the commencement of the expe- riment, but at its termination it was much exhausted, and the respiration became gasping. The blood formed a very strong inflammatory crust. The blood of a healthy ox,^ and of a healthy calf, yielded the followins: results : Water Analysis 50. 795-000 Analysis 51 777-279 Solid constituents 205-000 222-721 Fibrin — 2-600 Fat ... 5-590 4-191 Albumen 95-050 83-925 Haematoglobulin 91-710 105-925 Extractive matters and salt s 11-181 24-444 In the former of these analyses, the fluid which was examined, was a mixture of arterial and venous blood, from which the fibrin had been previously removed: in the latter case the ex- tractive matter was not separated from hsematin. The number 105-925 represents the globuKn perfectly free from colouring matter. [Andral, Gavarret, and Delafond, have published a valuable essay on the blood of some of our domestic animals in health and disease. They made no less than 222 anatyses of the blood of 155 animals, viz. 41 analyses of the blood of dogs, 31 of horses, 110 of sheep, 2 of goats, 23 of oxen and cows, and 7 of swine. ' Berzelius (Tbierchemie, p. 98) found, in the serum of the blood of oxen — water 905, albumen 80, albuminate of soda and lactate of potash 6-2, chloride of potassium 2-6, and modified alljumen ■with carbonate and phosphate of potash 1-5. BLOOD. 341 In order to give an idea of tlie composition of the blood in the different species of animals, we shall communicate the average, maxima, and minima numbers that were obtained. For the principles on which the analyses are founded, see p. 211. Analyses of the blood of 17 horses gave the following results: Fibrin. Blood-corpuscles. Residue of serum. Water. Mean 4-0 102-9 82-6 810-5 Maximum 50 112-1 91-0 833-3 Minimum 3-0 81-5 74-6 795-7 Analyses of the blood of 14 neat cattle yielded: Fibrin. Blood-corpuscles. Mean . . 3-7 99-7 Maximum . 4-4 117-1 Minimum . 3-0 85-1 Residue of scrum. Water. 86-3 810-3 93-6 (.') 824-9 82-9 799-0 The mean results of the blood of 6 bulls (1), and of an equal number of milch cows (2), indicated no important differences. (2.) Fibrin. Blood-corpuscles. 3-6 97-4 3-8 101-9 Residue of serum. Water. 85-8 813-2 86-8 807-5 Analyses of the blood of 6 swine of the English breed yielded Fibrin. Blood-corpuscles. Mean . . 4-6 105-7 Maximum . 5-0 120-6 Minimum . 4-1 92-1 The blood of 2 goats gave : Mean Maximum Minimum Fibrin. 3-2 3-5 2-6 Blood-corpuscles. 101-4 105-7 97-2 Residue of serum. 80-1 88-7 73-6 Residue of serum. 91-4 92-0 . 90-8 Water. 809-6 816-9 793-9 Water. 804-0 809-2 798-8 Sheep of various breeds appeared to differ slightly in the composition of the blood. Analyses of the blood of 19 sheep of the Eambouillet^ breed yielded Fibrin. Blood-corpuscles. Residue of serum. Water. Mean . 31 98-1 83-5 815-3 Maximum 3-8 109-6 96-6 830-3 Minimum 2-6 82-5 74-7 808-7 The blood of 11 sheep of a crossed variety, (the Naz-Ram- bouillet breed,) yielded : — A variety of the Merino sheep. 342 CIRCULATING FLUIDS: Fibrin. Blood-corpuscles. Residue of serum. Water. Mean . . 2-8 lOG-1 80-3 810-8 Maximum . 3-4 123*4 87-7 827-2 Minimmu . 2-3 94-6 74-7 789-8 The mean results from the blood of these 30 sheep were : Fibrin. Blood-corpuscles. Residue of serum. Water. 3-0 101-1 82-4 813-5 The blood of 13 English sheep yielded somewhat different results : Fibrin. Blood-corpuscles. Residue of serum. Water. Mean . . 2-6 950 92-4 810-0 Maximum . 3-3 110-4 97-0 822-1 Minimum . 2-0 83-8 82*6 795-3 From the blood of 16 dogsi they obtained : Fibrin. Blood-corpuscles. Residue of serum. Water. Mean . . 2-1 148-3 75'5 774-1 Maximum . 3-5 176-6 88-7 795-5 Minimum . 1-6 127*3 60-9 744-6 The blood was found to offer considerable differences in breeding animals before and after dehvery : Sheep 36 hours before dehvery „ 66 hours after delivery „ 24 hours before dehvery „ 72 hours after delivery Cow 5 days before dehvery „ 2 days after dehvery . That the blood of the lamb differs considerably from the blood of the parent sheep, is obvious from the following analyses: Fibrin. Blood-corpuscles. Residue of serum. Water. 2-3 95-0 81-7 821-0 3*0 106-2 78-2 812-6 2*9 92-9 84-5 819-7 3-5 102-6 86*3 807*6 3-7 90-9 75-2 830*2 5-1 98-8 73-7 822*4 Fibrin. Blood-corpuscles. Residue of serum. Water. lamb, aged 3 hours . 1*9 108-6 63-3 826-2 „ 24 hours . 1*9 117-0 74-2 806-9 „ 48 hoiu-s . . 2*5 103*3 80-7 813-5 „ 96 hours . 3-0 109-1 68-6 819-3 The maxima^ minima, and average numbers quoted above, are sufficient to prove that the blood of different species of ani- mals varies in its composition from that of man and of each ' GmeUn (Ilandbuch der theoretischen Chemie, vol. 2, p. 1387) found, in the arterial blood of a dog — water 898, and fibrin 2-09 ; the dried serum contained, albumen 88-3, and salts 11*7 ; the venous blood contained, water 843, and fibrin 2*1 ; the dried residue of the serum consisting of albumen 87-5, and salts 12-5. BLOOD. 343 other. This is a point of no slight importance, for it indicates the necessity that exists for the determination of the consti- tution of the healthy blood in every individual class of animals before we can venture to draw any conclusions regarding the blood in a morbid state. The mean amount of fibrin in one class of animals is as low as 2-1, while in another it rises to 4*6 per mille, one being considerably lower, the other much higher, than in man. The largest amount of fibrin observed by Andral, Gavarret, and Delafond, was in swine, the maximum being 5-0, and the minimum 4'1; the animals were from 2 to 6 months old, and had been restricted for some time to a diet of horse-flesh. In a two-year old sow that had been fed purely on vegetables, and was very fat, the fibrin did not exceed 4*0. The blood of horses ranks next to that of swine in the amount of fibrin, the observed mean being 4*0, the maximum 5-0, and the minimum 3-0. Next to horses come neat cattle, the mean amount of fibrin in their blood being 3-7, the maximum 4-4, and the mi- nimum 3-0. The blood of the bull does not contain a larger amount of fibrin than the blood of the cow or the ox. The blood of the Merino sheep contains on an average the same amount of fibrin as human blood, i namely, 3-0; in the blood of English sheep a smaller amount of fibrin was obtained. The smallest quantity of fibrin was found in the blood of dogs, the mean being only 2-1, the maximum 3-5, and the minimum 1*6. The minimum occurred in dogs feeding on an exclusive animal diet. From these observations it is evident that each class of animals contains in its blood its own standard amount of fibrin. The blood-corpuscles are found to occm-, for the most part, in an inverse ratio to the fibrin ; that is to say, in blood that con- tains a large amount of fibrin, the amount of the corpuscles is small, and vice versa. It was shown by special experiments that there is no connexion between the strength of the animal and the amount of fibrin. The amount of fibrin varies consi- derably before delivery and immediately afterwards, during the milk-fever J in the former case it is at its minimum, in the latter it attains its maximum. The amount of solid residue of the serum varies between 75-5 and 92-4. The former number occiu-s in the blood of the ' Aiulral and Gavarret alwavs refer to Lecann's standard. 344 CIRCULATING FLUIDS: dog ; the blood of swine, oxen, and Merino sheep, contains from 80-0 to 860, and the maximum occurs in the blood of the Enghsh sheep. The investigations of these chemists relating to the blood of domestic animals in a morbid state, were principally confined to sheep suffering from watery cachexia. ^ We extract the fol- lowing analyses from their essay, as illustrative of the changes that the blood undergoes in pure hydrsemia without any complication. Blood- Residue Fibrin. corpuscles. of serum. Water. A 5-year old sheep 1st Venesection . 3-1 44-8 52-7 899-4 „ 2d » . 30 42-2 50-9 903-9 A 6-year old sheep : 1st >» . 3-5 46-7 69-5 880-3 „ 2d „ . 3-5 46-6 70-7 879-2 A 6-year old sheep : 1st )> . 2-8 49-1 59-1 889-0 ,, 2d „ . 2-6 42-4 55-9 899-1 » 3d „ . 2-9 40-1 58-1 898-1 >» 4th „ . 2-8 67-7 66-6 862-9 A 5-year old sheep : 1st „ . 2-4 39-4 63-4 894-8 ») 2d „ . 2-3 33-3 55-8 908-6 »» 3d » . 3-0 29-3 52-1 915-6 » 4th „ . 30 14-2 51-9 930-9 The sheep, whose blood formed the subject of the last ana- lyses, died shortly after the 4th venesection. In those cases in which the hydrsemia was associated with inflammatory aflfections, the blood presented very different cha- racters, as the following analyses will show : Blood- Residue Fibrin. corpuscies. of serum. Water. A 5-year old sheep : 1st Venesection . 9-6 32-9 791 878-4 „ 2d „ . 6-4 300 78-6 885-0 A 4 -year old sheep : 1st „ 12-6 39-5 94-1 853-8 „ 2d „ 10-4 34-2 89-1 866-3 „ 3d „ 8-7 25-3 92-3 8/3-7 A 4-year old sheep : 1st >» . 5-7 60-1 99-1 835-1 „ 2d „ . 4-3 54-6 95-9 845-2 The first of these animals had, in addition to the hydrsemia, pneumonia and pulmonary abscess ; the second, acute hepatitis and peritonitis; and the third, acute bronchitis. The following analyses of the blood of sheep, with various disorders, were made by the same chemists : ' Commonly known as the rot. BLOOD. 345 niood- Residue Fibrin. corpuscles. of serum. Water. Sheep with acute bronchitis . 5-2 610 109-4 824-4 Ram with softened tubercles 4-4 88-8 101-8 8050 Sheep with tubercular pulmonary ca\1ty . G-2 64-5 106-7 822-6 Ram -with acute enteritis 6-0 100-7 96-6 796-7 Ewe with acute metritis 6-3 100-4 85-4 807-9 Sheep with chronic peritonitis : 1st Venes. 3-3 63-2 57-6 875-9 2d „ 3-2 58-8 52-2 885-8 3d „ 31 52-8 52-6 891-5 They remark that the changes which the blood of these animals undergoes in disease, precisely correspond with those of human blood in similar disorders. Thus, in inflammatory diseases, there is always an excess of fibrin, and they observe that in those animals in which the normal mean amount is highest, the fibrin is increased in the greatest proportion; thus in the blood of a cow with inflammation of the respiratory or- gans, the fibrin rose to 13"0, the normal amount in that animal being 3-8. In dogs that were reduced to a very anaemic con- dition, the blood-corpuscles fell from the normal mean 148, to 104, and even down to 83. Their attention was, however, principally directed to the watery cachexia, or rot in sheep. The most prominent phe- nomena of the disease were extreme debihty, paleness of the mucous membranes, and very frequently serous infiltration of the conjunctiva, and of the cellular tissue of the integument of the feet. No albumen was detected in the urine. From 27 analyses made with the blood of 11 sheep, they conclude that the amount of fibrin is slightly afi'ected, but that the blood- corpuscles are excessively diminished ; from 78, their normal average, they fall to 40, 25, and even 14. The solid residue of the serum is diminished, (a point in which this disease diff'ers from chlorosis in the human subject,) and the water is consi- derably increased. The deficiency in the amount of blood-corpuscles appeared to vary with the progressing weakness of the animal. By proper food, and due attention to atmospheric influences, the corpuscles were observed to increase; in one instance they rose from 49 to 64. From 14 analyses of the blood, in which this afifection was associated with inflammatory disorders, it appeared that the 346 CIRCULATING FLUIDS fibrin increases, and the blood-corpuscles diminish^ as in simple, uncomplicated inflammations. Lastly, they observed that when venesection was frequently had recourse to in inflammatory aff'ections, each venesection tended to increase the amount of fibrin and of water, and to diminish the quantity of blood-corpuscles. The following are the results of the first and last venesec- tions of a horse that was bled seven times in 24 hours : The 1st Venesection gave Fibrin. Blood-corpuscles. Residue of serum. 3-1 104-0 90-8 Water. 8021 7th „ . 7-6 38-3 601 894-2 Nasse has likewise taken up this subject since the pubhca- tion of Simon^s Chemistry. In the following analyses, which are extracted from his paper, the extractive matters of the blood and the insoluble salts ap- pear to be included with the albumen : Blood- Water. Fibrin. Fat. corpuscles. Albumen. Soluble salts Dog . 790-50 1-93 2-25 123-85 65-19 6-28 Cat . 810-02 2-42 2-70 113-39 64-46 7-01 Horse . 804-75 2-41 1-31 117-13 67-85 6-82 Ox . 799-59 3-62 204 121-86 66-90 5-98 Calf . 826-71 5-76 1-61 102-50 56-41 7-00 Goat . 839-44 3-90 0-91 8600 62-70 7-04 Sheep . 827-76 2-97 1-16 92-42 68-77 6-91 Rabbit . 817-30 3-80 1-90 170 72 6-28 Swine . 768-94 3-95 1-95 145-35 72-78 6-74 Goose . 814-88 3-46 2-56 121-45 50-78 6-87 Hen . 793-24 4-67 2-03 144-75 48-25 6-97 The following table represents the composition of the soluble and insoluble salts occurring in 1000 parts of the blood of these animals : Soluble salts : Dog Alkaline phosphates. 0-730 Alkaline sulphates. 0-197 Alkaline carbonates. 0-789 Chloride of sodium. 4-490 Cat 0-607 0-210 0-919 5-274 Horse 0-844 0-213 1-104 4-659 Ox 0-468 0-181 1-071 4-321 Calf 0-957 0-269 1-263 4-864 Goat 0-402 0-265 1-202 5-176 Sheep 0-395 0-348 1-498 4-895 Rabbit . 0-637 0-202 0-970 4-092 Swine 1-362 0-189 1-198 4-281 Goose 1-135 0090 0-824 4-246 Hen 0-945 0-100 0-350 5-392 BLOOD. 347 The insoluble salts were found by Nasse to be combinations of peroxide of iron, lime, magnesia, silica, and phosphoric and sulphuric acids. The magnesia and silica were not determined quantitatively. In 1000 parts of blood there were : I Dog Insoluble salts : 'eroxide of iron. Lime. 0-714 0-117 Phosphoric acid. 0-208 Sulphuric acid 0-013 Cat 0-516 0-136 0-263 0-022 Horse 0-786 0-107 0-123 0-026 Ox 0-731 0-098 0-123 0-018 Calf 0-631 0-130 0-109 0-018 Goat 0-641 0-110 0-129 0023 Sheep 0-589 0-107 0113 0044 Swine 0-782 0-085 0-206 0-041 Goose 0-812 0-120 0-119 0-039 Hen 0-743 0-134 0-935 0-010 The only animals in a state of disease whose blood was ana- lysed by Nasse were sheep with chronic rot (hydrsemia or watery cachexia), and horses with the glanders. The blood of three sheep affected with the disease in question gave the following results : The sheep a was very much reduced, and the blood had much the appearance of reddened serum. There was effusion into the peritoneum. The sheep b was pregnant, and in bad condition ; while the sheep c had been delivered about 10 weeks previously, and had been since attacked with dropsy. The salts were determined individually, but they presented no peculiar deviation from the normal standard. The following analyses refer to the blood of two horses a and B, suffering from chronic ozoena (the glanders) : Water A. . 952-00 B. 932-30 C. 916-00 Fibrin 2-75 3-84 3-90 Fat . 0-23 0-25 0-30 Blood-corpuscles . Albumen 10-20 27-52 23-40 32-02 31-25 39-45 Soluble salts 7-30 8-19 7-10 Water . 1. 833-00 A. 2. 860-00 3. 842-00 1. 859-00 t. 2. 816-00 Fibrin . 8-90 7-50 6-60 8-70 7-90 Blood-corpuscles Albumen and fat 65-50 86-58 43-30 83-68 68-20 76-70 44-20 82-27 88-50 81-65 Soluble salts 6-02 5-52 6-50 5-38 5-95 52-650 66-570 50-324 2-936 5-385 3-721 3-490-1 9-277 i 13-920 -| 0-829 J I 16-509 348 CIRCULATING FLUIDS: The individual salts did not differ in any remarkable degree from the normal standard. We have already had occasion to refer to the labours of Enderlin, in connexion with the chemistry of the blood. He has recently pubHshed the following analyses of the ash of the blood of various animals, which are confirmatory of the views to which we have more than once alluded, respecting the non- existence of lactates in the blood. The analyses are calculated for 100 parts of ash : Salts soluble in water : Ox. Calf. Sheep. Hare.' Tribasicphosphateof soda (3NaO,P05) 16-769 30-180 13-296 28-655 Chloride of sodium .... 59-340 \ Chloride of potassium . . . 6-120 J Sulphate of soda . . . . 3-855 Salts insoluble in water : Phosphates of lime and magnesia , 4-190 Peroxide of iron and phosphate of ditto 8-277 Sulphate of lime, and loss . . . 1-449 The alkaline carbonates in Nasse's analyses are easily ac- counted for by Enderlin's explanation of the action of the atmosphere on the tribasic phosphate of soda.] I have analysed the blood of the carp and of the tench. In both fishes it was tolerably clear, contained oil-globules visible to the naked eye, formed a loose gelatinous clot, from which scarcely any serum separated, and yielded, on whipping, a viscid sort of fibrin, possessed of little tenacity, and which, on the ad- dition of water, separated into minute flocculi, consisting (ac- cording to microscopic investigation) of granular masses and of minute vesicles far smaller than the nuclei of the blood-cor- puscles. The blood coagulated imperfectly on boihng, and was remarkable for its small amount of hsematoglobulin. The blood of bufo variabilis presented exactly similar phenomena ; but on a chemical examination it was found to be richer in solid con- stituents, especially in albumen, than the blood of fishes. It was impossible to form a quantitative determination of the fibrin or of the colouring matter in the blood of these animals, in ' In another analysis lie found bibasic phosphate of soda. BLOOD. 349 consequence of the aplastic character of the former constituent, and the minute quantity of blood that could be obtained. The analyses gave : Analysis 52. Water .... Solid constituents Fibrin .... Fat .... Albumen Hffimatoglobulin Extractive matters and salts Carp's blood. 872-000 128-000 a trace 2-967 83-850 24-635 6-129 Analysis 53. Tench's blood. 900-000 100-000 a trace 4-670 68-800 15-650 2-770 Analysis 54. Blood of bufo variabilis. 848-200 151-800 a trace 9-607 112-330 29-753 2-429 On boiling the dried residue of the blood with spirit, after the removal of the fat, I obtained tinctures of a deep red colour, such as Avould have been yielded by the blood of the mammalia, but they differed in this respect, that they did not become turbid on cooling, and the hsematoglobulin, instead of being deposited in flocks, had to be determined by evaporation. As the flesh of these animals differs from that of the mammalia, it is by no means impossible that there are corresponding differ- ences in the globulin and haematin. The large amount of al- bumen in the blood of bufo variabilis may perhaps be attributed to the unavoidable mixture of the blood with lymph, and per- haps with mucus. Dumas and Prevost analysed the blood of numerous animals. The blood was allowed to coagulate, the clot and serum were separately dried, and the serum that remained entangled in the clot was deducted, and added to the serum that spontaneously separated. The fibrin was not determined. Water. Solid constituents. Blood-corpuscles. Residue of serum. Ape : Simla CaUitriche 776-0 224-0 146-1 77-9 Dog 810-7 189-3 123-8 65-5 Cat 795-3 204-7 120-4 84-3 Horse 818-3 181-7 92-0 89-7 Calf 826-0 174-0 91-2 82-8 Sheep 829-3 170-7 93-5 77-2 Goat 814-6 185-4 102-0 83-4 Rabbit . 837-9 162-1 93-8 68-3 Guineapig 784-8 215-2 128-0 87-2 Raven 797-0 203-0 146-6 56-4 Heron 808-2 191-8 132-6 59-2 Duck 765-2 234-8 150-1 84-7 Hen 779-9 220-1 157-1 63-0 . 797-4 202-6 155-7 46-9 . 863-7 136-3 68-8 72-5 . 886-2 113-8 48-1 65-7 846-0 154-0 60-0 940 778-8 221-2 150-6 80-6 . 884-6 115-4 69-0 46-4 350 CIRCULATING FLUIDS: Water. Solid constituents. Blood-corpuscles. Residue of serum. Pigeon . Trout . Eelpout Eel Land-tortoise Frog [We have already alluded to tlie occurrence of animalcules in human blood : in the blood of the lower animals such cases are very frequently observed. Cercaria have been discovered in the blood by Mayer, and in his ' Dissertatio de Organo Electrico et de Hsematorosis ; Bonn. 1843/ he mentions the following : (1,) Paramoecium loricatum s. costatum, in frogs ; (2,) Amoeba rotatoria in fishes. i Polystoma-like animalcules were described by Schmitz as oc- curring in the blood of the horse. (Dissertatio de Vermibus in Sanguine. Berol. 1826.) Gruby and Delafond have described a peculiar animalcule of frequent occurrence in the blood of the dog, and numerous ob- servers have noticed similar phenomena in the blood of the horse and the ass.] The Lymph. Our knowledge of the chemical characters of the lymph is very deficient. It is described as a viscid yellow, greenish yellow, and occasionally red fiuid, devoid of odour, possessing a sKghtly saltish taste, an alkaline reaction, and containing from 3 to 5'7[] of solid constituents. The lymph of the human sub- ject is described by Miiller, Wurtzer, and Nasse as clear and of a yellow colour, while others assign to it the same tint, but assert that it is opalescent. It coagulates in the com-se of 10 or 15 minutes into a clear, tremulous, colourless jelly, and de- posits an arachnoidal coagulum of fibrin, which was previously held in solution, as in the liquor sanguinis, and is usually co- lourless, although Tiedemann and Gmelin have observed it of a reddish tint. The fluid left after coagulation is rather thick, resembles almond oil in appearance, and under the mi- croscope exhibits, even when perfectly clear, a number of colour- ' Valentin (MuUer's Archiv, 1841, p. 436,) frequently detected this animalcule in the blood of the salmon, and once met with it in the fluid of the cerebral ventricles. LYMPH. 351 less corpuscles, apparently smaller than human blood-corpus- cles, and far less numerous in it than the blood-corpuscles are in the blood. (Muller.) In addition to albumen, the serum of the hinph contains extractive matters and salts : the latter are the same as the salts of the blood. Gmelin found in 1000 parts of human lymph : Water 9610 Solid constituents 39'0 Fibrin 2-5 Albumen 27*5 Chloride of sodium, phosphates of potash and soda, and salivan' matter ..... 2-1 Extractive matters and lactate of soda . . . 6*9 Marchand and Colberg have analysed lymph obtained from a wound on the dorsum of a man's foot. They found in it : Water 969-26 Solid constituents 30-74 Fibrin 5-20 Albumen 4*34 Extractive matter 3'12 Fluid and crjstaUine fat 2*64 Chlorides of sodium and potassium, alkaline sulphates and carbonates, sulphate and phosphate of lime, and peroxide of iron 15-44 The amount of fibrin has doubtless been overrated in both these analyses, since the coagulum contains lymph-corpuscles, and some albumen, in addition to that constituent. In Marchand^s analysis it amounts to double the quantity in healthy blood. The quantity of albumen is also incorrectly stated, for a fluid containing -435 of albumen does not perfectly coagiJate on heating, as this fluid is reported to have done, but merely be- comes turbid, and deposits a few flocculi. The salts in ]\Iarchand's analysis amount to more than double the amount in the blood. [L'Heretier (Traite de Chimie Pathologique, p. 18,) analysed the lymph obtained from the thoracic duct of a man who died from softening of the brain, and who took nothing but a little water for 30 hours preceding his death. It contained in 1000 parts : 352 CIRCULATING FLUIDS: Water 924-36 Solid constituents 75-64 Fibrin 3-20 Fat . 5-10 Albumen 60-02 Salts 8-25] Dr. Rees has published an analysis of the lymph taken from the absorbents of a young ass immediately after death. He states its constituents to be : Water 965-36 Solid residue 34*64 Fibrin 1-20 Albumen 12-00 Extractive matter soluble in alcohol and in water . 2-40 Extractive matter soluble in water only . . 13-19 Salts 5-85 Fat a trace. The salts were alkaline chlorides, sulphates, and carbonates, with traces of phosphates, and of peroxide of iron. Lassaigne analysed lymph collected from the absorbents of the neck of a horse. He found in it, water 925*00, fibrin 3*30, albumen 57"36, chlorides of sodium and potassium, soda, and phosphate of lime 14-34. [The lymph collected from the absorbent vessels of the neck of a horse has been recently analysed by Nasse. He obtained in 1000 parts : Water 950-000 Solid residue 50-000 Albumen, with fibrin 39-111 Water-extract 3-248 Spirit-extract 0-877 Alcohol-extract 0-755 Ethereal extract 0-088 Oleate of soda 0-575' Carbonate of soda . 0-560 Phosphate of soda . 0-120 Sulphate of potash . 0-233 Chloride of sodium • 4-123^ Carbonate of lime 0-104' Phosphate of lime with some iron 0-095 Carbonate of magnesia 0-044 SUica . 0-067 ^5-611 ■0-310 LYMPH. 3r)3 It yielded no microscopic indications of urea. Nasse compared the lymph with the serum from the 1)lood of a healthy horse, and found a remarkable coincidence in the salts of the two fluids : Serum. Lymph. Alkaline chlorides . . . 4-055 4-123 Alkaline carbonates' . . . 1-130 1*135 Alkaline sulphates . . . 0-311 0-233 Alkaline phosphates . . . 0'115 0-120 5-611 5-611 The lymph, therefore, is a dilute serum, and the salts of the blood which make their escape along with the colourless liquor sanguinis from the capillaries, either return again in the same proportions to each other as they were secreted, into the capil- laries, or, which is most probable, they only penetrate into the lymphatic vessels. Besides, there being more water in the lymph than in the serum (in the ratio of 950 to 922) the two fluids differ in the ratio of their solid constituents to the salts; in the lymph, the salts amount to 11 "22, and in the serum to 9*65g of the solid residue. It is probably this circumstance that causes the much greater viscidity of the serum, which is by no means solely dependent on the larger quantity of albumen in solution.] All investigations with respect to the motion of the lymph in the absorbents, and to the origin and formation of the lymph- corpuscles, have hitherto been comparatively fruitless. Since the primitive cells of the tissues are now regarded as organized individuals possessing self-dependent powers of selecting their own nutriment, and of discharging the function of secretion, we can no longer refer the passage of the lymph into the ter- minal points of the absorbents to mere physical endosmosis and exosmosis. I do not believe that we can altogether satisfactorily refer the motion of the lymph to a vis a tergo. Whether the lymph is propelled by a progressive contraction of the absorbent vessels, as is maintained by some physiologists, is uncertain; thus much, however, is undoubted, that there are numerous valves in the interior of the Ij'mphatics to prevent the regur- gitation of their fluid contents. From Weber's observations, it appears that in the tadpole the motion of the lymph is from 10 to 20 times slower than that of the blood. ' The oleate of soda is calculated as a carhonate. 23 354 CIRCULATING FLUIDS: The Chyle. True chyle, that is to say, the emulsive fluid that is found after digestion in the lymphatic vessels of the intestinal canal, is usually turbid, and of a white or pinkish tint, but I once observed it of a blood-red colour. It is usually obtained for the purpose of analysis from the thoracic duct, when, although termed chyle, it is in reality a mixtm-e of lymph and true chyle. Chyle, like l}Tnph, coagulates in the course of from 8 to 15 minutes. The clot is soft, gelatinous, and either white (from the entangled fat-vesicles) or red (in consequence of the pre- sence of blood-corpuscles.) The fibrin obtained by whipping fresh chyle is deficient in consistence, being sometimes merely gelatinous, and cannot be washed without suffering loss. The serum of the chyle appears, from my observations, (which were instituted with the chyle of horses) to contain four different sorts of corpuscles, viz. («) fat- vesicles which occur in large numbers in milky chyle ; [b) blood-corpuscles, which may be numerous, few, or absent, according to circumstances; (c) round, colourless, transparent, rarely granular globules, from one half to three fourths the size of blood-corpuscles; I have never ob- sen^ed them in the blood ; they are the true lymph-corpuscles ; and [d] round, gray or colourless granular corpuscles, with a clearly defined, and not tuberculated outline, half as large again, or occasionally even twice as large as the blood-cor- puscles ; these are the chyle-corpuscles, which are always found in the blood. Fig. 12 exhibits chyle containing numerous blood-corpuscles as seen under the microscope. Human chyle has never yet been analysed, but several ana- lyses of the chyle of the lower animals have been made. Through the kindness of Professor Gurlt I have had several opportunities of examining the chyle of horses, and 1 have made three careful quantitative analyses of it. The method of analysis was pre- cisely the same as for the blood. The fibrin was removed in the usual manner, and washed. A known quantity of the serum was reduced to dryness, and the water thus determined ; the residue was finely pulverized, and a portion repeatedly treated with ether, and afterwards with spirit of '915 in order to remove the fat. It was then boiled in water. The residual albumen was dried and weighed. The spirituous and aqueous CHYLE. 355 solutions were mixed and evaporated, and the residue treated with water and dihite spirit, which took up the salts and extractive matters, and left the h?ematoglobulin. The extractive matters were dried, weighed, and incinerated, and the salts thus determined. The thoracic duct of a horse that had been kept without food for some time contained only a very small quantity of a reddish fluid, with an alkaline reaction, from which a slight fibrinous coagulum separated, and which, on standing, deposited a red sediment, while the supernatant fluid was clear and yellow. Blood-corpuscles were detected in the sediment, but they were not numerous, and, for the most part, altered in form. Lymph- corpuscles and a very few chyle-corpuscles were observed ; some of the latter were of a remarkable size, and presented a resem- blance to conglomerate fat-cells. 1000 parts of this chyle left a solid residue of 39-5, of which 20 consisted of albumen, and 3-2 of oily fat. In order to obtain a larger supply of chyle, a horse was fed on peas steeped in water ; it was shortly afterwards bled to death, and the chyle collected from the thoracic duct. I obtained upwards of 600 grains of a reddish yellow alka- line fluid, which was immediately stirred, in order to separate the fibrin. In the serum there was comparatively little fat, and only a small number of blood-corpuscles ; Avhile, on the other hand, the lymph- and chyle-corpuscles were abundant. None of the large conglomerate cells observed in the former chyle could be detected. The analysis of this chyle yielded : Analysis bb. Water 940-670 Solid constituents 59-330 Fibrin 0-440 Fat 1-186 Albumen 42-717 Haematoglobulin 0-474 Extractive matters and salts .... 8-360 Ptyalin, and globulin or casein, with chloride of sodium and lactate of soda .... 1-780 The analysis of the salts was not carried out. The amount of sohd constituents, and especially of albumen, is considerably larger than in the former instance, but the quantity of fat is remarkably small. 35G CIRCULATING FLUIDS: On a subsequent occasion I fed two horses with oats soaked in water, and analysed the chyle thus formed. Both spe- cimens were stirred, in order to remove the fibrin : they had an alkaline reaction, but one was turbid and milky, containing an extraordinary amount of soft but firm fat, while the other was of a blood-red colour, and contained a considerable number of blood-corpuscles. Both specimens contained lymph- and chyle-corpuscles. I have endeavoured, in fig. 12, to represent the corpuscles that were observed in the blood-red chyle. The analyses of these fluids yielded the following results : Analysis 56. Analysis 57. Milky chyle. Blood-red chyle. Water 928-000 910000 Solid constituents .... 72-000 84-000 Fibrin 0-805 0-900 Fat 10-010 3-480 Albumen witli lymph- and chyle-corpuscles 46-430 60-530 llaBmatoglohulin .... traces 5-691 Extractive matters .... 5-320 5-265 Alkaline lactates and muriates, mtli traces of lime 7-300 6-700 Sidphate and phosphate of hme and perox- ide of iron 1100 0-850 These analyses yield a much larger amount of solid consti- tuents than those quoted above : the increase is especially ob- servable in the amount of fat in the former, and in the con- joined amount of albumen and haimatoglobulin in the latter of these analyses. There can be no doubt that these variations are due partly to the nature of the food, and partly to the manner in which chylopoiesis goes on in aged or diseased ani- mals. The salts approximate closely, both in quahty and quan- tity, with those that occur in the blood. Dr. Bees analysed the chyle of the same ass to which refer- ence has been already made in page 352. It contained : Water 902-37 Solid constituents 97-63 Fibrin 370 Fat 3601 Albumen 35-16 Extractive matter soluble in alcohol and water . . 3-32 Extractive matter soluble in water only .... 12-33 Salts (similar to those in the lymph) . . . . 7-11 CHYLE. 357 [Nassei has instituted the following analysis of the chyle of the cat. It contained in 1000 parts : Water 9057 Solid constituents 94'3 Fibrin 1"3 Fat 32-7 Albumen, blood-corpuscles, and extractive matters . 48-9 Chloride of sodium .....•• 7*1 Other soluble salts 2-3 Iron traces Earthy salts 2-0 ] The elaborate treatise of Tiedemann and Gmelin affords much information respecting the influence of diet on the qualities of the chyle, and on the modifications that it undergoes in its passage through the mesenteric glands. Their analyses of the chyle of the horse are given in the following table : Solid Spirit-extract, Water-extract, Water, constituents. Clot. Albumen. Fat. with salts. with salts. 1 924-3 75-7 17*5 44-45 a trace 7-97 3-60 2 949-8 50-2 4-2 34-27 a Uttle 8-41 2-33 3 918-3 81-7 7-8 42-86 16-12 11-83 2-04 4 967-9 32-1 1-9 19-32 a little 9-19 0-94 5 948-6 57-4 31 24-27 1234 8-33 1-36 6 871-0 129-0 small 35-/5 87-07 3-22 7 959-0 41-0 24-60 (?) 1640 (?) 3-22 The first four analyses were made with chyle taken from the thoracic duct. The chyle in these cases separated into a bright red clot, and opaque, milky serum. The fifth analysis was made with chyle (taken from the same horse as in analysis 4) after its passage through the mesenteric glands, and the sixth analysis, with chyle, previous to its passage through them. In the former case, the chyle was of a bright red colour, and co- agulated perfectly, forming a pale red clot, and a reddish white serum ; in the latter, it was white, and coagulated very imper- fectly ; in fact, instead of there being a clot, there was merely a transparent yellowish film; the serum was white and milky. > Wagner's Handworterbuch, vol. 1, p. 235, article ' Chylus.' 358 CIRCULATING FLUIDS: In the seventh analysis, the chyle was collected from the ab- sorbents of the colon. The fat in these various specimens of chyle was partly solid, and partly fluid; the salts were apparently the same as in the lymph. The albumen left about 2'^ of ash, which consisted of equal parts of carbonate and sulphate of lime, together with a little carbonate, hydi'ochlorate, and sulphate of soda. The di'ied clot in analysis 2, yielded 9*07^ of brownish red ash, consisting of carbonate, sulphate, and muriate of soda, carbonate and phosphate of lime, and peroxide of iron. Tiedemann and Gmelin have communicated the following data regarding the influence of diet on the chyle. Their expe- riments were made on dogs, and the chyle was taken from the thoracic duct. 1. After taking cheese the chyle coagulated very slightly. The clot was little more than a pale red transparent film, and the serum was slightly milky. The chyle contained water 950-3, clot 1-71, residue of serum 48-0. 2. After the use of starch, the chyle was of a pale yellowish white colour, and coagulated rapidly. It contained water 930-0, clot and residue of serum 70-0. The clot was of a pale red colour. 3. After taking flesh, and bread and milk, the chyle was of a reddish white colour, and coagulated rapidly, the clot being of a pale red tint and the serum very milky. It consisted of water 915-3, clot 2-7, and residue of serum 83-8. 4. After the use of milk, the chyle presented a milky ap- pearance, and the clot was transparent and of a pale red colour. 5. After bread and milk, the chyle contained water 961*1, clot 1-9, and residue of serum 37*0. 6. After flesh, bread, and milk, the chyle Avas of a yellowish red colour, coagulated firmly, (separating into a bright red clot, and turbid yellow serum,) and contained water 933-5, clot 5'6, residue of serum 60- 9. Any explanation of the results of these investigations would be superfluous, since it is obvious from them, that the food best adapted to dogs, viz. a mixture of flesh, bread, and milk, CHYLE. 359 yields the richest chyle, and increases the amount of clot. That the fibrin is formed in the chyle from the constituents of tlie food is perhaps less proliablc than that it is separated from the blood in the lymphatic glands ; possibly, chyle of different qualities may react with varying energy on the lymphatic glands. END OF VOL. 1. EXPLANATION OF PLATE I. Fiy. 1. Blood-corpuscles of men, birds, and amphibia. 2. The formation of the blood-corpuscles, from Reichert. 3. Urea precipitated from an alcoholic solution by nitric acid. 4. Crystals produced in the alcohol-extract of blood devoid of urea, after the addition of nitric acid. 5. Nitrate of urea from blood in morb. Brightii. 6. Urea precipitated from an alcoholic solution, by oxalic acid. 7. Crystals produced in the alcohol-extract of blood devoid of urea, after the addition of oxalic acid. 8. Crystals of oxalic acid, resembling pure urea. 9. Nitrate of soda. 10. Crystalline groups of nitrate of urea, as it crystallizes from an alcoholic solution. 11. Pus in blood. 12. Chyle from the thoracic duct. I' II I N T E D BY C. AND J. A 1) L A R IJ, nARTIlOT.llMKW CUKE, O (C', i'V 'Q ^■:.- Oo-'U aife. 8^J%^ ^ 7t? B^' '© LIST OFFICERS AND MEMBERS THE SYDENHAM SOCIETY FOR THE YEAR ENDING MARCH 25th, 1845. LIST OF THE OFFICERS AND MEMBERS OK THE SYDENHAM SOCIETY rOR THE YEAa ENDING MARCH 25th, 1845. JOHN AYRTON PARIS, M.D.,F.R.S., President of the Royal College of Physicians WILLIAM PULTENY ALISON, M.D., F.R.S.E., Professor of Medicine in the University of Edinburgh. JOHN BLACKALL, M.D., Physician to the Devon and Exeter Hospital. Sir BENJAMIN C. BRODIE, Bart., F.R.S., Serjeant-Surgeon to the Queen. Sir WILLIAM BURNETT, M.D., F.R.S., K.C.H., Inspector-General of the Fleets and Hospitals. JOHN BURNS, M.D., F.R.S., Professor of Siugery in the University of Glasgow. WILLIAM FREDERIC CHAMBERS, M.D., F.R.S., K.C.H., Physician to the Queen and to the Queen Dowager. Sir JAMES CLARK, Bart., M.D., F.R.S., Physician to the Queen and to H.R.II. Prince Albert. Sir PHILIP CRAMPTON, Bart., F.R.S., Surgeon-General to the Forces in Ireland. ROBERT J. GRAVES, M.D., M.R.I.A., Physician to the Meath Hospital, Dublin. Sir JAMES M'GRIGOR, Bart., M.D., F.R.S. L. cScEd. Director-General of the Medical Department of the Army. JOHN HAVILAND, M.D., Regius Professor of Physic in the University of Cambridge. JOSEPH HODGSON, F.R.S., Surgeon to the General Hospital, Birmingham. HENRY HOLLAND, M.D., F.R.S., Physician Extraordinary to the Queen, and Physician to H.R.H. Prince Albert. JOHN KIDD, M.D., F.R.S., Regius Professor of Medicine in the University of Oxford. BENJAMIN TRAVERS, F.R.S., Surgeon Extraordinary to the Queen, and Surgeon in Ordinary to H.R.II. Prince Albert. OFFICERS. Council HENRY ANCELL, Esq. JOHN CLENDINNING, M.D., F.R.S. JAMES COPLAND, M.D., F.R.S. JOHN DALRYMPLE, Esq. WILLIAM FARR, Esq. ROBERT FERGUSON, M.D. WILLIAM FERGUSSON, Esq. JOHN FORBES, M.D., F.R.S. WILLIAM AUGUSTUS GUY, M.B. THOS. HODGKIN, M.D., F.R.S. SAMUEL LANE, Esq. Sir GEORGE LEFEVRE, M.D., Knt. DREWRY OTTLEY, Esq. JONATHAN PEREIRA, M.D., F.R.S. BENJAMIN PHILLIPS, F.R.S. J. FORBES ROYLE, M.D., F.R.S. WILLIAM SHARPEY, M.D., F.R.S. HENRY SMITH, Esq. SAMUEL SOLLY, Esq., F.R.S. THEOPH. 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Bridge Evaus, Thomas, esq. Bai'nes, Thomas, m.d. Cartmell, — m.d. Elliott, William, m.d. Page, W. B. esq. Wallace, Edward, esq. Dillon, J. M.D. Underwood, T. m.d. Hamerton, Clement, m.d. Taylor, James, m.d. Smyth, C. S. m.d. Roe, George, m.d. Blyth, Alexander, esq.. Wye Convict Ship Duirs, William, esq., Melville Hospital Ely, George, esq. Ford, W. M., for Library, Port Pitt Martin, Richard, W. m.d. Rae, William, m.d., Melville Hospital 2 10 SYDENHAM SOCIETY, Cheadle, Staffordshire . Cheadle, near Manchester Chelmsford Cheltenham Chertsey Chesham, Bucks Chester Chesterfield Chichester Chilcompton Chippenham Cirencester Clay, Norfolk Clitheroe . Cloghjordan Clonmel Colchester . Coleraine, Ireland, Local See. Bourne, John E. esq. Newbury, B. esq. Tomkinson, Richard, esq. Ockleston, R. esq. . Miller, Samuel, m.d. Local Sec. Colledge, Thomas R. m.d. Acworth, E. m.d. Allardyce, J. m.d. Bagnall, G. m.d. Bernard, W. R. esq. Cannon, yEneas, m.d. " Cary, Walter, esq. Coniyn, S. E. m.d. Conolly, William, m.d. Copeland, G. F. esq. Eves, A. W. esq. Fowler, Charles, esq. Goodlake, Henry Cox, esq. Hawkins, Clement, esq. Murley, Stephen H. esq. Pinching, Charles J. esq. Shaw, C. S., esq. Thomas, R. C. m.d. Thorpe, Disney L. m.d. Harcourt, George, esq. . Hodgson, John Bolton, esq. Local Sec. M'Ewen, W. esq. Jones, Pliillips, m.d. Harrison, John, esq. Weaver, John, esq. Willmott, A. M.D. . Booth, Charles, esq, Holland, John, esq. Walker, Hugh Eccles, m.d. Local Sec. Tyacke, Nicholas, m.d. Buckell, Leonard, esq. CafSn, WiUiam Chart, esq. Duke, Abraham, esq. Gruggen, John Price, esq. Gruggen, H. M. esq. M'Carogher, J. m.d. Woodman, James, m.d. Flower, Farnham, esq. Colborne, Wm. esq. Warner, Thomas, esq. Cooke, Corbett, Charles, esq. Garstang, J. esq. Purefoy, — m.d. Kemphill, — jun., m.d. Local Sec. Williams, Edward, m.d. Bewick, Robert, esq. Johnson, Walter, esq. Philbrick, Samuel A. esq., /or Medical Library. Babington, Thomas H. m.d. Macaldin, J. J. m.d. Mac Longhlin, Edward P. esq. Hall, John, esq. CoLLON, County of Meath Congleton . . Local Sec. Conisborough, near Doncaster Fisher, Henry, esq Cork . . Local Sec. Popham, John, m.d Finn, Eugene, m.d. LIST OF MEMBERS. 11 Cork {continued) CoTFORD, near Sudbury . Cove ..... Coventry . . Local Sec. CowES, Isle of Wight CowBRiDGE, Glamorganshire CowFOLD, near Horsham Cranbourxe, Dorset Cranbrook, Kent Cratvley Crayford, Kent . Crewkerne Cricklade, Wiltshire Croydon cuckfield . CuLLOMPTON, Devon Darlington. Dartmouth, Devon Dawlish .... Derby . . . Local Sec. Devonport .... Devizes . . Local Sec. Diss Doncaster . Dorking .... Douglas, Isle of Man . DowNHAM Market Dover . . . Local Sec. Harvey, J. 11. m.d. Harris, Walter, m.d. O'Connor, Denis Charles, m.d. Osborn, Thomas, juu., m.d. Townsend, E. R. m.d. Bailey, W. K. esq. Meade, Horace, N. m.d. Scott, David H. m.d. Troughton, Nathaniel, esq. Arrowsmith, Robert, m.d. Barton. F. W. esq., /or Medical Library Laxon, William, m.d. Peach, William, m.d. Phillips, E. esq. Tierman, — esq. Cass, William, esq. Hoft'meister, William Carter, m.d. Sylvester, Charles, m.d. Gravely, Thomas, esq. Hobsou, Smith, esq. Smart, Thomas William, esq. Ranger, Frederick, esq. Smith, Thomas, esq. Grantham, John, esq. Bowdage, Emanuel, esq. Taylor, Thomas, esq. Berry, Edward, esq. Westall, Edward, esq. Byass, Thomas Spry, esq. Maunder, William H. esq. Harper, Alfred, m.d. Piper, Stephen Edward, esq. Strother, Arthur, esq. Burrough, R. F. esq. Cann, W. Moore, esq. Fox, Douglas, esq. Evans, Samuel, esq. Fearn, S. W. esq. Greaves, Augustus, esq. Heygate, James, m.d. Johnston, Whittaker, esq. Rudkin, J. C. esq. Worthington, Henry, esq. Crossing, T. esq. Swaine, P. esq. Seagram, Wm. B. m.d. Trinder, Charles, esq. Montgomery, Ronald, esq. Anstie, Thomas Brown, esq. Ward, Heniy, esq. Scholfield, Edward, esq. Storrs, Robert, esq. Hindle, James, esq., Norton Curtis, George, esq. Sutherland, Patrick, m.d. Oswald, H. R. esq. Wales, Thomas G. esq. AsTLEY, Edward, m.d. Coleman, Thomas, esq. Heritage, 0. F. esq. 12 SYDENHAM SOCIETY. DoA'ER (confinved) Droitwich, Worcestershire Drogheda . Uronfield, Derbyshire Dublin Local Sec. Dudley DULWICH Dumfries Hutchinson, Scrope, m.d. Jones, Edward, esq. Mercer, Thomas, esq., Deal. Rutley, G. E. esq. Soulhy, J. M.D. Stolterforth, Sigismnnd, m.d. Ecikins, Clement, esq. Topham, John, m.b. Fogarty, — m.d. Clarke, Thomas H. esq., CliflF House Nicholson, J. esq. Law, Robert, m.d., 54, Rutland square Aicken, Thomas, m.d., 68, Marlbro' street Bankes, John T. m.d. m.r.i.a. Barker, William, m.d. Benson, C. m.d. Bevan, Philip, esq., 1, Hatch street Bindon, II. Vereker, esq. Brady, Thomas, m.d. Carmichael, Richard, esq. Crampton, Sir Philij), Bart. Carte, Alexander, m.d., 62, Upper Bagot street Cooke, Howard, m.d., 72, Blessington street Cusack, James, m.d. Croker, Charles P. m.d. Duncan, J. F., m.d. Dwyer, Henry L. m.d. Evans, John, m.d. Green, George, m.d. Graves, Robert J. m.d. Ilargrave, William, m.d. Harvey, J. m.d. Hutchinson, William, m.d. Ilutton, — M.D. Hunt, P. M.D. Irvine, H. esq. Kennedy, H. m.d. Mollan, J. M.D. Marsh, Sir Henry, Bart. M'Donnel, J. m.d. Nehgan, J. M. m.d. O'Keefe, Cornelius, esq. Regist. of Coll. of Siin/eons O'Reardon, John, m.d. O'Reilly, Richard, esq. Patten, J. esq., Kildare street. Royal Dublin Society Sargent, Richard J. m.d. Smyly, Joshua, esq. Steel, W. Edward, m.b. Walsh, Albert, m.d. . Cartwright, Cornelius, esq. Fereday, Samuel, esq. Houghton, John H. esq. Tinsley, William, esq. . Ray, Edward, esq. Loc. Sec. Browne, W. A. F. m.d. Barker, William L. m.d. Grieve, James, m.d. M'Culloch, James M. m.d. M'Lachlan, James, m.d. M'Lellan, R. H. m.d. LIST OK MEMBERS. 13 DUNDKE DUNDONALI) .... DuNGANNON, t'ovuty Ti/roiie . Durham . . Loc. Sec East Grinsted, Sussex East Rudham, Norfolk East Stonehouse, Devon Edinburgh . . Local Sec Loc. Sec. Monro, William, m.d. Aitkin, William, esq. Arnott, James, m.d. Bell, Alexander, m.d. Cocks, Robert, m.d. Nimnio, Matthew, esq. Osljornc, G. M. m.d. Alexander, William, m.d. Nevill, William, esq., m.h. Jepson, C. Edward, es([. Alexander, — m.d. Boyd, William, esq. Caldcleugh, S. esq. Games, John, esq., Blackgalc Croudace, George, escj., Rainton gate Cuninghame, W. esq. Dodd, — esq. Green, William, esq. Hepple, Matthew, esq. Stoker, W. esq. Ilopton, — esq. M'Larin, — esq. Trotter, John, m.d. Oliver, N. esq. Robson, Robert, esq Tyler, Edwin, esq. W^atkin, Thomas Laverick, m.d. Covey, George, esq. Manby, Frederick, esq. Upjohn, Francis Robert Smith, esq. Sheppard, James, esq. Spittal, Robert, m.d., 16, Howe street Abercrombie, John, m.d., The late, 19, York place- Alison, W^. P. M.D., 44, Heriot row- Ballingall, Sir George, m.d., 13, Ileriot row Beath, John, esq., 19, Castle street Begbie, James, m.d., 6, Ainslie place Bennett, John Hughes, m.d., 5, Scotland street Black, Francis, m.d., 19, Lynedoch place Brown, John, m.d., 51, Albany street Combe, J. S. m.d., 35, Charlotte street, Leith Cormack, John Rose, m.d., 131, Princes street Gumming, William, m.d., 15, Elder street Da\idson, Joshua H. m.d., 19, Abercrombie place Dickson, A. W'. esq., 14, Great King street Douglas, Haliday, m.d., 15, Drummond place Duncan, James, m.d., 12, Heriot row Gilchrist, William, m.d., 53, Constitution st. Leitii Goodsir, H. D. S. esq., 21, Lothian street Haldane, Daniel R. esq., 24, Drummond place Hamilton, Robert, m.d., 7. Nelson street Hardie, Gordon, K, 19, Salisbm-y street Henderson, William, m.d., 63, Northumberland st. Henderson, M. W. m.d., Corstorphine Holden, Ralph, esq., 15, Dundas street Hunter, Adam, m.d., 18, Abercroinby place Jackson, Alexander, m.d., 20, Clarence street Johnstone, James, W. F. m.d., 22, Albany street Keith, G. S. m.d., 22, Albany street Keiller, A, m.d., 18, St. Patrick square 14 SYDENHAM SOCIETY. Edinburgh {continued) Elgin, North Britain . Eling, near Southampton Elland, Halifaa; . Eltham, Kent Ely .... Emsworth, Hants Enfield, Middlesex Epping .... Epsom .... Evesham .... Exeter, Devon . Local Sec. ExMouTH, Devon . Kennedy, John, m.d., the late, 29, Broughton street Laud, George, m.d., 271, Clarence street Lonsdale, Henry, m.d., 2, Teviot row ^Macfarlane, John, F. esq., 17, North Bridge street Mac Lean, John, m.d. 17, Queensferry street Malcohn, R. B. m.d., 76, George street Marshall, Henry, esq., 25, Albany street Mercer, James, m.d., 50, Northumberland street Millar, James S. esq., 9, Roxburgh street Miller, James, esq., 22, St. Andrew square Moir, John, m.d. 52, Castle street Pagan, Samuel Alexander, m.d. 3, Melville street Paterson, R. m.d., 8, QuaUty street, Leith Pattison, P. H. m.d., 1, Leopold place Robertson, James, esq., Westtield, Cramond Scott, John, M.D., 45, Queen street Simpson, James Y. m.d., 22, Albany street Smyttan, George, m.d., 20, Melville street Sommerville, Samuel, m.d., 17, Hart street Stiven, W. S. m.d., Penniciiick Tait, W. M.D., 37, Nicolson street Taylor, John, m.d., 1, Abercrombie place Treasurer of Royal Coll. of Phi/s., 119, George st. Treasurer of Royal Med. Soc, Surgeon's square Treasurer of Hunterian Med. Soc. University University of Edinburgh Library Walker, W. esq., 47, Northumberland street Waters, Edward, esq., 14, Elder street Wilkinson, D., m.d., 5, Howe street. Paul, John, m.d. Spear, Wilham, esq. Hamerton, John, esq. Scholefield, John B. esq. Guillemard, Isaac, m.d. Muriel, John, esq. Miller, George, esq. Miller, John, esq. Taylor, WilUam G. esq. Merriman, Charles, A. esq. AUan,John, esq. Jones, Arthur O'Brien, esq. Stillwell, George, esq. Martin, Anthony, esq. Porter, John H. m.d. Pennell, Richard Lewin, m.d. Blackall, John, m.d. Delagarde, P. C. esq. Empson, WiUiam, esq., Clist-Hydon Granger, F. m.b. HaU, William, m.d. Kingdon, W. D. m.d. Marsden, James, m.d. Meny, W. H. esq.. Broad Clyst Miles, Erasmus, m.d., Heavitree Parker, J. B. esq. Shapter, Thomas, m.d. Shaw, Henry, esq. Black, Glass, m.d. Kane, William, esq. Land, William H. esq. Spettigue, John, esq. LIST OF MEMHEKS. 15 Fairford, Gloucestershire Falkirk Falmouth . Fanet, Ireland Farringdon, Berks. Farningham, near Dartford Farnham, Surrey . Filey, near Scarl/oro', Yorks. FiNCHINGFIELD, EsseX Folkestone, Kent Forfar FowEY, Cornwall . Frampton-on-Severn, Glou- cestershire . FuLBECK, Grantham Grampound, Cornwall Garstang, Lancashire Gateshead . Gedding, Woolpit, Suffolk Glasgow . . Local Sec. Glasslough. Co. of Motiaghan Gloucester . . Local Sec. Cornwall, Charles, esq. Espie, J. esq. BiiUniore, F. C. esq. Fullerton, J. W. esq. Maiitell, George, m.d. Harris, Henry, esq. Hunt, F. U. M.D. Knowles, E. Y. esq. Ne\\iiliam, William, esq. Cortis, William S. esq. Owen, W. B. esq. Minter, — esq. Steele, William, esq. Bennet, William P. esq. Watts, Thomas, esq. Smith, Christopher B. esq. James, R. esq. Bell, William, m.d. Barkiis, B. esq. Brady, H. esq. Dixon, G. esq. Wliite, W. Middletou, m.d. Fleming, J. G. m.d. 121, West Regent street Adams, J. M. esq. Anderson, Andi'ew, m.d. Anderson, A. D. m.d. Black, J. W. esq. Brown, James, m.d. Burns, John, m.d. Couper, John, m.d. Findley, John, m.d. Frazer, D. r.n. Gowdie, John, esq. Hall, Alfred, m.d. Hutcheson, W'illiam, m.d. Jeffray, James, m.d. Lancey, Thomas, esq. Laurie, J. A. m.d. Macewan, John, m.d. Macfarlane, John, m.d. Macned, Neil, m.d. Mackie, Andrew, m.d. Maund, John, esq. Orr, R. S. m.d. Pagan, J. M. m.d. Parker, Robert, esq. Pollock, John, esq. Pritchard, Thomas, es(|. Rainey, Ilan-y, m.d. Smith, David, m.d. Thomson, William, m.d. University Library, per Questor Watson, James, m.d. Weir, William, m.d. Wright, William, esq. Maifett, Richard, m.d. Hitch, S. m.d.. Lunatic Asylum Cockin, John, esq. 16 SYDENHAM SOCIETY. Gloucester (continued) GODALMING GooLE, Yorkshire GOSPORT Grantham .... Gravesend .... Great Grimsby, Lincolnshire Great Yarmouth Greenock .... Greenwich . Guildford .... Guernsey . . Local Sec. Haddington, N.B. Halifax, Yorks. . Local Sec. Halstead, Essex . Hanley, Staff. Han well, Middlesex Harewood, near Leeds Harlington, 7iear Exeter H arrow-on-H ill Harrowgate Haslar, Portsmouth Hastings Hatfield . . Local Sec. Haverfordwest, South Wales Hawkhurst, Kent Hawarden, Flintshire Helmsley, York . Hemel Hempstead, Herts . Cookson, John, esq. Hicks, Thomas, esq. Rumsey, H. W. esq. Wood, Alfred, esq. Chaudler, A. Thomas, esq. Cass, William Eden, esq. Jenkins, John, esq. Richardson, John, esq., Haslar Hospilal Rundle, William John, m.d. Brown, Joseph, m.d. Armstrong, John, esq. Keetley, Thomas Bell, esq. Worship, Harry, esq. Spiers, John, m.d., Killblain square Maccall, T. S. m.d. Barclay, Henry, esq. Burton, J. M. esq.. Groom's Hill Greenwich Hospital Purvis, P. m.d. Sells, Thomas Jenner, esq. Stedman, James, esq. Ozanne,Jos. esq. Howden, Thomas, m.d. Lorimer, Rol)ert, m.d. Garlick, John William, m.d. Alexander, William, m.d. Bramley, Lawrence, esq. Inglis, James, m.d. Jubb, Abraham, sen. esq. Kenny, Mason Stanhope, m.d. Robertshaw, Thomas, esq. Sowerby Bridge Robinson, John, esq., Ripponden Stansfield, Geo. esq. Tucker, F. Hosken, esq. Gilson, Benjamin, esq. Dale, James, esq. Begley, W. C. m.d., T. C. D. Smith, Gregory, esq. Cheesewright, William, esq. Curtis, H. Charles, esq. Hewlett, Thomas, esq. Berry, Grove, esq. Kennion, George, m.d. Stead, H. C. esq. Anderson, — m.d. Allen, James, m.d. Salmon, James, esq. Stewart, Alexander, esq. Duke, William, m.d. Ilobson, Smith, esq, Mackuess, James, m.d. Moore, George, m.d. Ranking, Robert, esq. Savery, John, esq. Thomas, William Lloyd, esq. Warlow, William, esq. Young, Francis Ayerst, esq. Moffat, John, m.d. Ness, John, esq. Merry, Robert, esq. LIST OF MEMBERS. 17 Henfield, Sussex . IIenley-in-Arden Hereford . Local Sec. esq. Hertford Local Sec. Heywood, near Bury, Lane. Hexham HiTCHIN HOLBEACH HoRBURY, near Wakefield HORNSEY HoRSFORTH, near Leeds Horsham Houghton-le-Spring, Durham HOUNSLOW .... Hull Local Sec. HuLME, near Manchester Huntingdon . Local Sec. hurstpierpoint Hyde . Morgan, Frederick, esq. Biruiiiii, n. F. m.d. Iiigs, John, esq. Braii invAiTE, Francis, Archibald, Kohcrt, esq. Bull, Henry Graves, m.d. Cam, Thomas, esq. Farmer, John, esq. Gilliland, William L. m.d. Hanhiiry, George, esq. Lingen, Charles, esq. Lye, John Bleek, m.d. Scriven, John Barclay, esq. Smith, Robert, esq. Taylor, Theophilus, esq. Vevers, H. jun. esq. Waudby, Samuel, esq. Wright, Henry Goode, esq. Davies, John, m.d. Phillips, George Marshall, esq. Reed, Frederick George, esq. Towers, G. A. esq.. Infirmary Leach, Jesse, esq. Nicholson, John, esq. Foster, Oswald, esq. Shillitoe, R. R. esq. Vise, E. B. esq. Robinson, Charles, esq. Hands, Benjamin, esq. Wilson, William M. esq. Bourn, Thomas, esq. Martin, Thomas, esq. Coleman, W. T. m.d. Green, Samuel, esq. Tweddell, William, esq. Emmott, C. B. esq. Cooper, Henry, m.d. Clark, J. H. esq., Aldbrough Gordon, W. m.d. Hardey, Robert L esq., Charlotte street Horner, F. R. m.d. Huntingdon, Frederick, esq. Locking, Jos. Agar, esq. Lunn, Wm. Jos. m.d. Riggall, Edward, esq. Sandwith, II. m.d. Sandwith, G. esq. Sharpe, Richard, esq., 9, Castle row Sharp, William, esq. f.r.s., Iliuuber Bank Sleight, R. Leadam, esq. Twining, Edward, esq. Wallis, Edward, esq. West, Charles Turner, esq., 8, North street Bowman, D. esq. Foster, Michael, esq. Foster, M., for Medical Library Isaacson, Wootton, esq. Wilson, Josiah, esq. Holman, Henry, esq. Tinker, William, esq. 18 SYDENHAM SOCIETY Ingatestone Inverness . Ipswich Ironbridge .... Jarrow .... Keith, Banffshire . Kenton, Devon Kettlethorpe, Lincolnsh. Kidderminster . Local Sec. Kilmarnock Local Sec. Kingsbridge, Devon Kingston-on-Thames . Kington, Herefordshire Kingstown, Ireland Kirkaldy, Fifeshire KiRKHAM KiRKSTALL, near Leeds Knaresborough . Knowle Knutsford, Cheshire Lancaster Leamington Leatherhead Leeds Local Sec. Local Sec Butler, C. H. esq. Walker, John, m.d. Baird, A. W. m.d. Beck, Edward, m.d. Bulleu, G. esq. Duriant, C. H. m.d. Scott, Walter, esq. Webster, W. II. B. esq. Rodeii, Sergeant, esq. Rowland, J. W. esq. Brown, W. W. esq. Christie, John, m.d. Day, J. A. esq. Waddington, Edward II. esq. Roden, William, m.d., f.l.s. Bradley, Thomas, esq. Jotham, George William, esq. Philbrick, Cornelius James, esq. Roden, Thomas Clarke, esq. Taylor, Thomas, esq. Thursfield, Thomas, esq. Ward, the Lady, Iliraley Hall Hood, Alexander, esq. Aitkin, James M. C. esq. Mitchell, John, esq., Mauchline Paxton, John, m.d. Rodger, WilHam, esq., Galston Thompson, John, esq. Young, Robert, esq. Elliott, John, esq. Cox, Abram, m.d. Marshall, G. Henry, esq. Adams, William, m.d. Philp, John, esq. Gradwell, William, esq. Shaw, Thomas, esq. Bishop, Edward, esq. Newton, Isaac, esq. Kimbell, J. H. esq. Gleeson, E. M. esq. Gaskell, Samuel, esq. De Vitre, — m.d. Howitt, Thomas, esq. Ricketts, Charles, esq. Beesby, Ralph A. esq. Ebbage, Thomas, esq., Portland street Franklin, Francis, m.d. Jephson, J. m.d. Jones, Richard, esq. Starr, T. II. m.d. Nash, William L. esq. , Teale,T. P. esq. Allanson, James, esq Bearpark, G. E. esq. Braithwaite, W. esq. Brown, C. F". esq. Bulmer, George, esq. Cass, W. R. esq. Chadvvick, Charles, m.d. Chorley, Henry, esq. LIST OF MEMBERS. 19 Lekds (continued) Leek Lenham Lerwick, Shetland Leicester . Lewisham LiFF Lincoln Limerick .... LiTCHAM, near Swaffham Liverpool . . Local Sec. . Drennan, J. S. M.n. Evans, Evan, esq. Garlick, J. P. esq. Hall, Matthew, esq., Wortley Hay, William, jun. esq. Hey, Samuel, esq. Hey, "William, esq. Hopper, R. S. m.d. Hobson, Richard, m.d. Irvine, G. W. m.d. Jackson, Matthew, esq. Land, Thomas, esq. Leeds School of Medicine Mayne, George, m.d. Morley, George, esq. Nunneley, Thomas, esq. Price, William, esq. Radclirte, C. B. esq. Rickards, G. H. L. esq. Smith, Pyemont, m.d. Smith, Thomas, m.d. Staniland, Samuel, esq. Teale, Joseph, esq. . Cooper, Richard, esq. Heaton, Charles, esq. Stickiugs, George, esq. . Cowie, John, esq. Local Sec. Barclay, John, m.d. Buck, John, esq. Harding, Heury, esq. Harding, H. eiq., for Leicester Infrntunj Macaulay, Thomas C. esq. Paget, Thomas, esq. Seddon, William, esq. Stallard, J. H. esq. Swain, Thomas, esq. . Steel, C. Vs. esq. . Archibald, David, esq. . Local Sec. Hainworth, John, esq. Broadbent, Edward Farr, es([. Hadwen, Samuel, esq. Hewson, John, esq. Hill, R. Gardiner, esq. Gritfin, William, m.d. Raven, Peter, esq. VosE, J. m.d. Anderton, Henry, esq. (Wootton) Bainbrigge, W. H. esq. Bickersteth, Robert, esq. Byerly, Isaac, esq., 93, Prescot street Chalmers, D. esq. Chapman, M. J. m.d. Dickinson, Joseph, m.d. Dnsdale, J. J. m.d., 44, Rodney street Dudgeon, Robert, m.d., 17, Oxford street Ellison, King, esq. Inman, Thomas, m.b. Lewis, Thomas, esq., 2 Rodney street Liverpool Medical Institution 20 SYDENHAM SOCIETY. Liverpool {continued) Llandilo, South Wales. Liverpool Infirmary Long, James, esq., 10 Rodney street Pearson, J. Annitage, esq. (Woottou) Smith, John Bromley, esq., 59, Great George street Swinden, Edward, esq., Wavertree Prothero, — m.d. Samuel, Williairj, esq. LONDON LIST. Abraham, Thomas, esq. Adams, John, esq. Adcock, Christopher, esq Addison, Thomas, m.d Adlard, C. & J., Messrs. Allchiu, W. H. esq. Allen, W. esq. Alhiatt, Richard H. m.d. Ancell, Henn', esq. Ansell, Thomas, esq. Appleton, H. esq. Archer, WilUam, esq. Arnott, Neil, m.d. Ashley, W. H. esq. Ash-well, Samuel, m.d. Atkinson, John Charles, esq. Ayre, William, esq. Babington, B. G. m.d. B.ibington, R. esq. Baker, Frederick ]\L esq Balfour, Thomas Graham Ball, R. de Champs, esq Ballard, Thomas, esq. Ballard, Edward, m.d. Bartr, F. esq. Barnes, Alfred, esq. Barnett, Thomas, esq. Bartlett, William, esq. Basham, Wilham R. m.d Bateman, H. esq. Baxter, Heniy F. esq. Baylis, Edward, esq. Beale, Miles, esq. . Bean, Edward, esq. Beane, Joseph M. esq. Beck, J. S. esq. Bell, Jacob, esq. Bennett, James Risdon, : Bently, Edward, esq. Beny, Edward Unwin, esq Bevan, Thomas, m.d. Bibby, Samuel, esq. Bird, James, esq. 49, Old Broad street. City 31, New Broad street. City 28, Charles terrace. New Cut, Lambeth 24, New street, Spring gardens Bartholomew close University College 9, Albion place, Hyde park 4, Parliament street 3, Norfolk crescent, Oxford square Bow Lower Clapton 1, Montague street, Portman square 38, Bedford square 1, Grove villa, Loughboro' road, Brixton 16, Grafton street, Bond street Romney terrace, Westminster Hackney 31, George street, Hanover square London University Hospital 11, North place, Kingslaud road St. James's square 12, Bloomsbm-y square 81, Connaught terrace 2. King Edward terrace, Islington Portland place, Clapton Gloster house. King's road, Chelsea 72, Fore street, Limehouse 19, Netting hill terrace 17, Chester street, Pimlico 9, Church row, Islington 5, George street, Hanover square 30, Sackville street, Piccadilly Bishopsgate street Camber\\ell Peckliam 53, Upper Marvlebone street, Portland place 338, Oxford street 24, Finsbury place, north 35, Trinity square. Borough 7, James street, Covent Garden Finsbury circus 9, North Audley street 16, Orchard street, Port man sfpiare LIST OF MEMBERS. 21 Bird, Goliling, m.d. Bird, Henry, escj. . Birkett, John, esq. Birkctt, E. L. m.b. Blenkarne, Henry, esq. . Biewitt, Octavian, esq. . Blundell, James, m.d. Bonipas, Joseph C. esq. Bostock, John, m.d. Boyd, Robert, m.d. Bristowe, John Syer, es(i. Brodhurst, B. Edward, esq. Brodie, Sir Benjamin C. IJart Brodribb, W. P. esq. Brown, C, Blakley, m.d. Brown, Isaac Baker, esq. Brown, J. Hallett, m.d. . Brown, R. F., esq. Brown, Robert, esq. Brown, Thomas, esq. Brown, Robert, esq. Brown, William, esq. Brjant, Walter, J. esq. . Buchanan, G. A. esq. Buckland, J. Pelham, esq. Bull, Thomas, m.d. Burnett, Sir W. m.d. k.c.h. Burton, Henry, m.d. Bush, — m.d. Butler, James, esq. Callaway, Thomas, esq. . Campbell, Alex. Elhott, m.d. Camplin, John, esq. Camps, W. m.d. Camps, W. M.D. Carr, James Thomas, esq. Cart\\Tight, Samuel, esq. Chambers, William F., m.d. Chepmall, E. C. m.d. Chichester, J. H. R. esq. Child, G. C. m.d. Chohueley, W. esq. Chowne, W. D., m.d. Churchill, J. esq. Clark, Fred. Legros, esq. Clark, Sir James, Bart. . Clarke, J. F. esq. Cleland, A. esq. Clementson, F. L. esq. . Clendinning, John, m.d. Clifton, N.H. esq. Clissold, Rev. Augustus . Cochrane, J. G. esq. Colebourne, Henry, esq. CoUyer, G. esq. Conquest, J. T. m.d. Cook, William, esq. Cooke, R. H. esq. Cooke, William M. m.d. Cooper, Bransby B. esq. Myddleton square M^'an cottage, Hampstead road 2, IJroad street buildings Cloak lane 39, Dowgate hill 73, Great Russell street, Bloomsbnry Great George street, Westminster University College 22, Upper Bedford place Marylebone Intirraary Camberwell 4, St. Helen's place, Bishopsgatc. 14, Saville row 12, Bloonisbun* square 3, John street, Berkeley square 39, Counauglit terrace 7, St. George's p'ace, V/alworth roatl 2, St. Mary Axe 37, Euston square 13, William street, Knightsbridge Brixton hill 22, Russell place, Fitzroy square 50, Edgeware road 50, Myddleton street, St. John street road 84, Watling street 27, Fiiisbury place The Admiralty 41, Jermyn street Kensington House Seething lane. Tower street Wellington street, London bridge First Life Guards 1 1 , Finsbury square 50, Green street, Grosvenor square for Parisian Medical Society St. Thomas's Hospital 32, Old Bm-lington street 46, Lower Brook street 17, Hanover square 3. Stone buikUngS; Lincoln's inn Mortimer street St. Bartholomew's Hospital Princes street. Cavendish square Princes street, Soho Finsbury square 22 B, Lower Brook street 23, Gerrard street, Soho 118, Cock hill, Ratclitf 6, Warwick Villas, Maida hill 16, Wimpole street 38, Cross street, Islington Stoke Newington London Librar>-, 29, Pall Mall 28, Harlej'ford place, Kenningtou 24, Old street road 13, Finsbury square St. Thomas's hospital Church street, Stoke Ne\vington Trinity square. Tower hill 2, New street, Spring Gardens 22 SYDENHAM SOCIETY. Copland, James, m.d. Cotton, R. Payne, esq. Coulthred, James, esq. Comtenay, John, esq. Covey, Wm. Henry, esq. Coward, G. W. esq. Cox, W. Travers, m.d. Craigie, J. L. esq. . Crawford, Menyn, m.d. Crisp, Edwards, esq. Crompton, T. L. esq. Crowdy, Charles Wliitton, esq. Crowther, J. R. esq. Culpeper, Wdliam M. esq. Currie, Paul Francis, m.d. Curtis, J. W. esq. Daliymple, John, esq. Davies, Robert, esq. Davies, David, esq. Davis, J. Jones, m.b. Davis, Thomas, esq. Davis, Richard Sladen, esq. Day, G. E. m.d. De Morgan, Campbell, esq. Dendy, Robert, esq. Dendy, Walter C. esq. Derry, T. M. esq. Dewsnap, M. esq. Domeier, E. A. m.d., the late . Dover, Frederick, esq. Duncan, Edward, esq. Dunn, Robert, esq. Duthoit, Thomas John, esq. Eddowes, J. H. esq. Edwards, Henry-, esq. Edwards, Vertue, esq. Edwards, Daniel, esq. Ellam, John, esq. Erichsen, John, esq. Evans, J. 0. esq. . Eyles, John Brown, esq. Eyles, Richard Strong, esq. Eyre, Stratford A. esq. Farr, WilHam, esq. Farre, Arthur, m.d. Farre, Frederick, m.d. Ferguson, Robert, m.d. Fergusson, Wilhaui, esq. Fidler, J. esq. Finch, Richard S. esq. Fincham, George, m.d. Fisher, J. W. esq. Fitton, W. John, esq. Fitzpatrick, Francis, esq. Foote, John, esq. Forbes, John, m.d. Fox, Charles James, m.d. Frampton, Algernon, m.d. France, John, esq. Fraser, Patrick S. m.d. Old Burlington street 11, Kensington square 4, Melton street, Southwark Bridge road 5, Finsbury terrace 42, Charing Cross 2, North Road, Hoxton 2, Stanhope place Finsbury square 62, Upper Berkeley street 31, Beckford row, Walworth 29, Howland street, Fitzroy square Brixton hill 6, Lansdown place, Brunswick square Marylebone Infirmary 30, Brook street Finsbury pavement 56, Grosvenor street 126, Holborn Hill St. Thomas's Hospital 4, Poplar terrace. Poplar Hampstead 13, Chancery lane 3, Southwick street, Oxford square 17, Manchester street 2, Grafton street east, Tottenham Court road 10, Tillotson pi., Waterloo rd., for Land. Med. Soc. Westminster Hospital Hammersmith 39, University street 54, Great Coram street 3, Leadenhall street 15, Norfolk street, strand 22, Trinidad place, Islington St. Thomas's Hospital 67, Edge ware road St. Thomas's Hospital 13, Queen street, Cheapside 320, Rotherhithe street 48, Welbeck street University College 1, St. Andrew's court, Holborn 1 , St. Andrew's court, Holborn 3, Fitzroy street, Fitzroy square Registrar-General's Office Curzon street, May Fair 35, New Bridge street, Blackfriars road 9, Queen street. May Fair 8, Dover street 4, Camden row, Camberwell Marylebone Infirmary 38, Curzon street, May Fair Argyll street 52, Upper Harley street 27, Lisson street, New road 36, Tavistock street, Covent Garden 12, Old Burlington street 13, New Broad street. City 29, New Broad street, City 88, Cadogau place 62, Guildford street LIST OF MRMBERS. •23 French, J. G. esq. Fuller, Hugh, esq. Fuller, J. esq. Galtoii, Francis, esq. Gardiner, John, esq. Gardiner, Roger Cooper, Garrett, Mark 1?. esq. Garrod, A. B. m.d. Gavin, Hector, m.d. Gay, John, esq. George, J. D. esq. Gihson, John R. esq. Gillespie, Patrick, esq. Girdwood, Gilbert F. esq Godricli, Francis, esq. Goodfellow, S. J. m.d. Goodwin, J. M. esq. Gooldeu, R. H. m.d, Gordon, Adam, esq. Grainger, R. D. esq. Grant, N. m.d. Grant, John, esq. Gray, John, esq. Greenhalgh, Robert, esq. Greenwood, Henrv, esq. GritEth, J. W. m.d. Grimsdale, Thomas F. esq Guazzaroni, John, esq. Guest, Edmund, esq. Gull, ^V. W. M.B. Gulliver, George, esq. Gunthorpe, George John, Gu)% W. A. M.B. Hakes, J. esq. Hall, Marshall, m.d. Hamilton, Alfred, esq. Hanson, Sidney, m.d. Harding, J. F. esq. Hardwick, Alfred, m.d. Hardwicke, WiUiam, esq Harper, Robert, esq. Harris, Wintow, esq. Harris, Michael, esq. Harston, A. D. esq. Hastings, John, m.d. Haviland, — m.d. . Hawkins, Caesar, esq. Hawkins, James, esq. Hawkins, Charles, esq. Headland, Edward, esq. Heberden, W. m.d., the Heraing, G. 0. m.d. Henry, Alexander, esq. Hensley, L. esq. Hering, William, esq. Herring, ^yilliam, esq. Heisch, Frederick, jun., Hilton, John, esq. Hilton, John, esq. Hird, Francis, esq esq. esq. late esq. Marlborough street 53, King William street, City 48, Hertford street, May Fair 16, King street, Covent Garden 49, Great Portland street Cheyne walk, Chelsea ^, New Road, St. George's East Charterhouse square Thurlow place. Hackney road 12, Finsbury Pavement 32, Old Burlington street 115, Holborn hill Lisson Grove north 177, Maidahill Little Chelsea London Fever Hospital Streatham, Surrey 8, John street, Adelphi Surgeon R.N., 22, Surrey street, Strand St. Thomas's Hospital 21, Thayer street, Manchester square Bengal Anny, 71 a, Grosvenor street 7, Upper George street, Portman square 66, Upper Charlotte street, Fitzroy sq. Horsleydown lane 9, St. John's square Univsrsity College 3, Terrace, Kensington College street, Chelsea Guy's Hospital Roy. Reg. of Horse Guards 51, Newington place, Kennington Bloomsbury square 28, Duke street, Manchester square 14, Manchester square Broad street BuikUngs 17, Hanover square 13, Spencer street, Northampton square Kensington 12, Calthoqje street, Gray's Inn road 2, Conduit street, Westboiu-ne terrace, Hyde park 1, New Dorset place, Clapham road Paradise row, Hackney Trinidad place, Islington 14, Albeniai-le street 177, Maida hill for Roy. Med. Chirurg. Soc. Berners street 36, Collett place, Commercial road Albany Court yard 32, Guildford street 28, Cumberland street, Bryanstone square 7 B, Manchester square 4, Carohne street, Bedford square 3, Great James street, Bedford square 14, Foley place 74, Sun street, Bishopsgate 16, America square for Medical Library, Guy's Hospital Guy's Hospital Cleveland row, St. James's 24 SYDENHAM SOCIETY. Hitchman, J. esq. Hoar, W. esq. Hocken, Edward, m.d. Ilodgkin, Tliomas, m.d. . Hodgson, Joseph, esq. . Holland, Henry, m.d. Holman, William H. esq. Holman, J. R. esq. Holman, Charles H. esq. Hopkins, John Morgan, m.d. Houlton, Joseph, jun. esq. Hovel, Thomas, esq. Howell, C. W. H. esq. . Hughes H. M. m.d. Hulm, Edwj'n St. James, m.d. Humby, Edwin, esq. Humphreys, William, esq. Hunt, Henry, m.d. Hutchinson, W. Barclay, esq. Hutchinson, Francis, esq. Huxtable, William, esq. . Jackson, Alfred, esq. Jackson, Thomas Carr, esq. Jacob, William, esq. James, W. P. esq. James, Henry, esq. Jay, Henry, esq. Jeaffreson, Henry, m.d. . Jeaffreson, John F. esq. . Jenkins, James, esq. Jervis, Thomas, esq. Jervis, George H. J. esq. Johnson, James, m.d. Johnson, Cavendish, esq. Jones, Thomas, m.d. Jones, Henry Derviche, esq. Jones, John Darlington, esq. Iliff, William T. esq. lUingworth, Henry, esq. Kaye, W. G. esq. . Keen, Thomas, esq. Kelsall, Thomas E. esq. Kesteven, Wilham, esq. Keyser, A. esq. Kilner, John, esq. King, Osraan, esq. . Kinnis, J. m.d. Lambert, H. esq. . Lammiman, R. W. esq. Lane, Samuel, esq. . Langmore, H. esq. Langmore, William, m.d. LangstafF, J. esq. . Lankester, Edwin, m.d. Latham, P. Mere, m.d. Lauder, William P. m.d. Law, Charles, esq. . Leeson, H. B. m.d. . Lefevre, Sir George, m.d. Leonard, Thomas, esq. m. Sanatorium, New road 78, Blackfriars road. 1 3, Bloomsbury square Brook street 1, Spital square, Bishopsgate street Without 2."), Lower Brook street 10, John street, America square ditto ditto 1, Elizabeth street, Eaton square 87, Lisson grove North Five Houses, Clapton Stratford-le-Bow 14, St. Thomas's street 1, Tonbridge place. Burton crescent Warwick villa, Maida hill 21, Upper Southwick street 68, Brook street 40, Guildford street 92, Faningdon street 1, Well's row, Hackney London University College St. Thomas's Hospital 31, Cadogan place 37, Euston square 4, City road 42, Sloane street 2, FinsbuiT square Canonbury square, Islington Royal Navy, 13, Clements lane 23, Edward street, Portman square 7, Kingsland green 8, Suffolk place, Haymarket 3, Norfolk crescent 19, Finsbury pavement 23, Soho square 1, Queen's road, Dalston 18, Canterbury row, Newington Butts 1, Arlington street Royal Navy IT), ]\Lanor place north, King's road, Chelsea Great Winchester street, City Upper llolloway 21, Norfolk crescent, Burwood place 33, Gower place, Euston square 37, Bernard street, Russell square Army St. Luke's Hospital, Old street road 118, Cock hill, Ratclitr 1 Grosvenor place 15, Upper George street, Portman square Finsbury square 9, Cambridge square, Hyde Park 19, Golden square 36, Grosvenor street 8, Sloane street 3, Artillery place, Finsbury square St. Thomas's Hospital 60, Lower Brook street, Grosvenor square 14, Aske terrace, Hoxton LIST OF MEMBERS. 25 Letheby, Henry, m.d. Lever, J. C. W. m.d. Lewis, David T. esq. Lewis, W. A. esq. Lister, Bryan, esq. Liston, Robert, esq. Little, W. J. M.D. . Lloyd, W. AV. esq. . Lobb, William, esq. Lockley, Thomas, esq. . Locock, Charles, m.d. Luke, James, esq. . Lonsdale, Edward, esq. . Mackintosh, James, esq. . Macmeikan, John, esq. . Maclachlan, Daniel, m.d. M'Gill, William, m.d. M'Gregor, Sir James, Bart. M'Intyre, 'William, m.d. . Maillardet, J. "\V. esq. Mann, John, esq. . Marshall, John, esq. Marson, J. F. esq. . Martin, J. R. esq. . Mathew, Charles Reeve, esq. Mathew, James Edward, esq. Mathews, R. N. B. jun. esq. Mercer, Thomas E. esq. Meridith, E. F. esq. Merriman, Jas. Nathaniel, esq. Merriman, John, esq. Merriman, S. W. J. m.d. Metcalfe, James B. esq. Miles, John, esq. . Miles, John Shirlev, esq. MiUer, C. 'SI. esq. . Milroy, Ga\in, m.d. Moger, Robert, esq. Moore, Joseph, m.d. Morley, Atkinson, esq. Munk, William, m.d. Murdock, William, m.d. Muriel, Charles, esq. Murphy, Edward W. m.d Nairne, Robert, m.d. Nasmyth, Alexander, esq Nelson, Duckworth, esq. Newell, H. A. esq. . Newton, Edward, esq. Nicolson, Thomas, esq. North, John, esq. . North, Robert Exton, esq. Noys, G. H. M.D. Nussey, John, esq. Olding, George, esq. Oldham, Henrys m.d. Ottley, Drewp,', esq. Owen, Richard, esq. Page, William E. m.d, Pardee, George, m.d. London Hospital Wellington street. Borough 182, Brick lane, Spitalticlds 18, Stratford i)lace. Cavendish square University College ChtFord street Finsbury scjuare 62, Great Russell street, Bloomsbury 12, Aldersgate street 6, St. George's place, Hyde Park corner 7, Hanover square 39, Broad street buildings for Library, Middlesex Hospital 32, Wilton place, Knightsbridge London Hospital Chelsea Hospital 2, Bentinck terrace, St. John's Wood 13, St. James's place 84, Hai-ley street 8, St. Martin's place. Charing cross 63, Bartholomew close 8, Crescent place, Mornington crescent Resident Surgeon, Smallpox Hospital, Charing cross 71 A, Grosvenor street London University College Church Cottage, De Beauvoir square, Kingsland 18, Canterbury row, Newington Butts University College, London 15, Charles street. West bourne terrace Kensington Kensington 34, Brook street Church street. Hackney 84, Harley street 8, Victoria square, Pimlico 1, Claremont terrace. Stoke Newington 30, Fitzroy square Highgate 10, SaviUe row Burlington Hotel, Cork street 2, Finsburj' place, south 320, Rotherhithe street 4, Wellington street, London bridge 12, Henrietta street. Cavendish square 44, Charles street, Berkeley square 13 A, George street, Hanover square London Hospital 13, Warwick court, Holbom 26, Howland street 33, Berkeley square 18, King street, Portman square 26, Cheyne walk, Chelsea Moorgate street 4, Cleveland row, St. James's 1.59, High street. Borough 13, Devonshire square, Bishopsgate 38, Hart street, Bloomsbuiy College of Surgeons 43, Curzon street. May Fair ."i3, Russell square 3 26 SYDENHAM SOCIETY. Paris, JohnAyrton, m.d. Peacock, Thomas B. m.d. Percivall, W. esq. . Percira, Jonathan, m.d. Perigal, Fredei-ick, esq. Perkins, Dodd, esq. Perkins, Houghton, esq. Perry, James, esq. Pettigrew, William V. m. Philp, Francis R. m.d. Phillips, Benjamin, esq. Phillips, James, esq. Phillips, Thomas, esq. Pilcher, George, esq. Pitman, H. A. m.d. . Poland, Alfred, esq. Pout, George, esq. . Powell, Henry, m.d. Powell, David, esq. Pyle, John, esq. Quain, Richard, m.d. Quain, Richard, esq. Redfearn, P. esq. . Ree, Henry P. esq. Reed, Septimus, esq. Rees, Henry, esq. . Reynolds, H. esq. . Rhys, Thomas, esq. Ridge, Joseph, m.d. Riding, Roger, m.d. Roberts, Charles I. m.d. Roberts, John, esq. Robins, William, esq. Robinson, James, esq. Robinson, Richard R. esq. Roods, Henry C. esq. Roots, H. S. m.d. . Rose, C. esq. . Ross, Daniel, esq. . Rowe, J. esq. Rowley, R. m.d. Royle, J. Forbes, m.d. Rust, Thomas, esq. Rygate, John James, esq. Samwell, Francis, esq. Sandon, James H. B. esq. Saunders, E. esq. . Savage, Henry, esq. Savory. John, esq. . Sawer, Thomas, esq. Scott, John, M.D. . Searle, G. C. esq. Seaton, Edward, m.d. Self, James, esq. Sharpe, Rd. esq. Shai-pey, William, m.d. Shute, Robert Greber, esq. Skey, Fred. C. esq. Smee, Alfred, esq. . Smith, Henry, esq. . Dover street 2, South place, Finsbury First Life Guards Finsbury square 33, ToiTington square St. Thomas's Hospital Mortimer street. Cavendish square 4, Eaton square, Pimlico 30, Chester street, Grosvenor place, Pimlico 28, Grosvenor street 17, Wimpole street Wliite House, Bethnal green 44, Albion street, Hyde Park 7, Great George street, Westminster Montague place, Russell square 21, Bow lane, Cheapside 65, High street. Borough 31, Finsbury square 21, Garnault place, Spa Fields 1, Middlesex place, New road University College Hospital, Gower street 23, Kepple street 13^, Newington Causeway Union place. City road 41, Jewin street. City 45, Finsbury square 42, Moorgate street University College Hospital 37, Cavendish square 36, Euston squai'e 31, New Bridge street, Blackfriars 34, Finsbury circus 16, Upper Southwick street 7, Gower street 4, Camden row, Camberwell 67, Great Russell street, Bloomslffury Russell square 10, Barnes place, Mile end 56, High street, Shadwell 41, Upper John street, Fitzroy square 37, King William street, City 4, Bulstrode street. Cavendish square 39, Connaught terrace London Hospital Margaret street. Cavendish square 36, Albemarle street 16, Argyle street 34, Dorset place, Dorset square 143, New Bond street 1, Lyon teiTace, Maida hill 12, Bedford square 42, Cumming street, Pentonville 77. Sloane street Mile end road Grange road, Bermondsey 35, Gloucester crescent, Regent's Park 27, Mecklenbm-gh square 13, Grosvenor street Finsbury cu'cus 17, Henrietta street. Cavendish square LIST OF MEMBERS. 27 Smith, Ebenezer, esq. Smith, John Simm, esq Solly. Samuel, esq. Squibb, George James, esq. Squire, WilUam, esq. Statham, Hugh, esq. Staunton, Charles F. m Stephen, T. esq. Stewart, A. P. m.d. Stewart, Haldane, esq. Stewart, Wm. Edward, jun. esq Stewart, Wm. esq. Stocker, James, esq. Stokoe, Richard, esq. Storks, Robert, esq. Stott, Thomas B. esq. Stowers, Noel, esq. Strickland, John, esq. Sutherland, Alex. J. m.d Swaine, W. E. m.d. Synnett, — m.d. Tanner, Thomas Hawkes, esq. Taunton, John C. esq Taylor, Edward, esq. Taylor, W. esq. Taylor, C. esq. Taylor, Jas. Eastwood, esq. Teavers, James, esq. Teevan, William, esq. Tegart, Edward, jun. esq Thompson, Theophilus, Thompson, Richard, esq, Thomson, Anth. Todd, m Thwaites, Thomas B. esq. Tibson, Arthur, esq. Todd, Robert B. m.d. Tomkias, C. Joseph, esq. Toulmin, Frederick, esq. Townsend, John A. esq. Toynbee, John, esq. Travers, Benjamin, esq. Treasurer of Medical Society Treasurer of St . George's Hospi Tripe, John William, esq. Tulloh, James St. m.d. . Turner, John, esq. . Tweedie, Alexander, m.d. Ure, Alexander, esq. Vade, John Knox, m.d. Varicas, R. A. esq. Vaux, J. m.d. Vincent, George, esq. Vinen, Edward Hart, esq. Waggett, John, m.d. Waite, Charles, esq. Walcott, Robert Bowie, esq Walker, George A. esq. . Wall, John P. esq. Wallace, R. esq. Walsh, Charles R. esq. . Billiter square 17, Trinity square, Tower hill 1, St. Helen's place, Bishopsgate 6, Orchard street, Portman square Wandsworth roatl Wandsworth road Royal Engineers, 40, St. Martin's lane King's College Library 130, Mount street, Berkeley square 55, Cadogan place Weymouth street, Portland place 1, Wells row, Hackney Guy's Hospital Peckham Rye 44, Gowcr street Aldersgate Uispensaiy 26, Albion street, Hyde Park 22, North Audley street 1 9, Fludyer street, Westminster 41, Foley place 8, Westbourne place, Eaton square King's College 48, Ilatton garden Clapham Common London University Hospital 18, Holland place, Clapham road 4, Caroline street, Bedford square 307, Rotherhithe wall 23, Bryanstoue square 37, Biyanstoue street, Portman square 3, Bedford square For London histitution, Finsbuiy 30, Welbeck sti-eet University College Hospital 1, Spring street, Paddington 26, Parliament street 9, Huntley street, Bedford square Upper Clapton 48, FinsbuiT circus Argyll place Bruton street University College, London tal Library 7, King's place, Bath street. Commercial road 3, Agar street. Strand 10, Bedford place, Russell square 30, Montague place, Bedford square 13, Chai'lotte street, Bedford square 8, Upper Seymour street, Portmau square 29, Wobourne place, Tavistock square Elm Cottage, Elm Grove, Hammersmith 109, Sloaue street 164, Blackfriars road 1, Norland terrace, Nottinghill 3, Old Bm-lington street 8, York street, Portman square 101, Drurj- lane 5, Mount street. Grosvenor square John's terrace, Hackney roa BINDING SEC, T. MAY 1 i 1^6/ QP Simon, Johann Franz 514. Animal chemistry with S563 reference to the physiology V.I and pathology of roan Biological k Medical PLEASE DO NOT REMOVE CARDS OR SLIPS FROM THIS POCKET UNIVERSITY OF TORONTO LIBRARY