f ■>i.' LIBRARY OF THE University of California. Class TEXT BOOK OF COMPARATIVE GENERAL PATHOLOGY FOR Practitioners and Students of Veterinary Medicine BY PROFESSOR DR. TH. KITT OF MUNICH Authorized Translation BY DR. WILLIAM W. CADBURY Assistant Demonstrator of Patholog:>' in the Universitj' of Pennsylvania Edited with Notes and Additional Illustrations BY DR. ALLEN J. SMITH Professor of Pathology in the University of Pennsylvania Illustrated with Four Colored Plates and One Hundred and Thirty-one Text Illustrations V" OF THE UNIVERSITY OF y CHICAGO CAvro^^}^^ W. T. KEENER & CO. 1 906 .^^ *V\., }vos, domestic ammsLl ; iarpdi, physician) and vcterinarii; Early History. ii yet in a large measure it remained in its primitive condition in the hands of shepherds and farmers. At the beginning of our present era medicine was chiefly domi- nated by the teachings formulated by Hippocrates and Aristotle in their general writings. The study of comparative natural science, instituted by Aristotle, laid the foundation of our knowledge of animal biology, of comparative anatomy and physi- ology ; while Hippocrates and after him the physicians of his school established pathology. At that time it was held that there were in the animal and hmuan bod)' four cardinal humors, "blood, mucus, and yellow and black bile." It was taught that a proper relationship between these (crasis) insured health; and that dis- ease depended upon the occurrence of lack or excess of one or other, that is upon some modification of their relationship (dys- crasis). Next to the blood, the principal vital humor, Hippocra- tes placed mucus in order of importance, because it is often dis- charged in large quantities from the nose and was thought to come from the brain and to escape through the ethmoidal open- ings. Yellow bile was often seen in vomit : but black bile was entirelv a product of the imagination and was supposed to arise in the spleen. The basis of vital phenomena was supposed to be the inspired air {pnciuna, the breath of life), which was thought to contribute warmth to the body. In conformity with the accepted theory of corruption of the humors, therapeutic measures were directed to a riddance from the system of the ma- terial which had caused the "dyscrasia ;" and for this reason evacuants, diaphoretics, diuretics and venesection played an mi- portant part in those times. The importance which Hippocrates ascribed to these fluids or humors led to the application by later generations of the name Humoral Pathology to this system. The solid structures of the body were not entirely disregarded, but only vague ideas prevailed in relation to them. There was a theory (Democrites) that the solid parts were made up of particles known as c.toms, between which there were pores [for the passage of air and humors], that the width of these pores varied with the varying density of deposition of the atoms, and that by some such method the state of the body was regulated. To this extent, therefore, there was a Solid Pathology, which, however, found but few adherents. Efforts toward such theoretical explanations found support particularly in the schools of philosophy ; and tenacity of such views and the rigid 12 History of Pathology. adherence to authority, together with constant seeking after the keenest dialectic in argument, gave to one school of physicians of the day the character of "dogmatists ;" while others discarded entirely speculative reasoning and called themselves "empiricists," boasting that their methods of practice were based entirely on experience. They rejected the study of anatomy as superfluous ; in which, however, the dogmatists, although essentially bookmen and theorists, made some progress. In the middle of the second century Claudius Galenus (born in Pergamon, Asia Minor, A. D. 131 ; educated in Smyrna, Corinth and Alexandria, and afterwards practicing his profession in Rome ; died A. D. 206), noted both for his discoveries and as a prac- titioner, revolutionized medical science by his efforts to harmonize the prevailing theories with practical experience and thus give them a real value, and by his work in the establishment of ra- tional scientific methods through comparative anatomy and ex- periments upon living animals. Throughout the middle ages, even into the fifteenth century, the theories of Galen, whose discoveries were numerous and whose extensive writings contain much that is of descriptive value, were held in esteem and respect, par- ticularly his opinions upon anatomy and physiology. Through studies of this character at the hands of physicians a close relationship developed between veterinary medicine and human medicine ; but there were other influences which aided in the development of comparative pathology. Agriculturists, like Xenophon, Cato, Columella, and Virgil, and veterinary specialists who in Rdman times attained an independent standing, and among whom should be mentioned Apsyrtos (circa 290-350, A. D.) and Publius Vegetius Renatus (circa 540, A. D.) as es- pecially distinguished, there were collected and recorded in litera- ture their experiences with various diseases, especially epidemic affections among animals. Although there is much useless em- piricism included in the dissertations of these writers, there are also no little excellence of observation and soundness of thought ; and the works of the last-named author, like those of Galen, served for centuries as valuable spurces of information. The general collapse of the sciences after the fall of the Roman Empire, during the time of migration of the European peoples and the period of the Middle Ages, resulted in a long stagnation in medicine. Practically all that is worth considering was the preservation of the writings of the ancients, for which we Middle Ages and Modern History. 13 are chiefly indebted to the monks, working as copyists in the monasteries. Technical medical skill made scarcely any note- worthy progress. With the founding of the universities in the thirteenth to fifteenth centuries, when a resumption of anatomical investigations gradually became possible, and with the discovery of the printing art, which stimulated the translation and wide 'dissemination of the works of Grecian and Roman authors, there began a new epoch. The luminous works of the human anato- mists like Vesalius, FaJlopius and Eustachius, the experimental researches of Serv^etus and Columbus Cesalpinus. and particularly William Harvey's (1578-1658) discovery of the true conception of the circulation of the blood, led directly to the recognition of the errors in Galen's system and to a reorganization of medical science.* As usual pathology again fell into errojr, ascribing, un- der the influence of prevailing views in natural science, the various processes of disease and their causation now to this, ndw to that physical or chemical factor. Speculative hypotheses took precedence of actual experiment, and attempts at proper explana- tion were quite lost in the fancies of the individuals. Some were followers of the "chemical school" founded by Sylvius, and en- deavored to explain every fault by chemical changes in the com- position of the bod\-, as the introduction of "sharps" (Boer- haave) ; others, the "neuropathologists," when the importance of the nervous system became .recognized, laid stress upon the in- fluence of the nerves (William Cullen), or upon the eflrect of "stimuli" and the irritability of the tissues (the theory of ex- citability of Haller and Erown). Others, basing their views upon mechanics, believed the vital phenomena of morbid disturbances depended upon mechanical faults of relationship ("mechanical school," founded by Santoro, 1 561-1635, Borelli, 1608-1677). Still others spoke of "vital spirits" circulating in the body, of "forces," of the power of the "entities" (Paracelsusf). or made some injury to the immortal soul the real principle of disease (G. E. Stahl. 1660-1734). These doctrines were denominated wVa/- ism and airiiiiism. Such ideas have found adherents even as late as within the nineteenth century, clothed usually in high-sounding foreign verbiage to make the greater impression. Along with these speculative theories, however, exact clinical •Compare Eichbaum, GachicMe df HcilJ;undc: Berlin. Pareys' Verl.. 1SS5. tTheophrastus Bombastus, whose proper name was Paracelsus, distinguished different forces, an ens astrale (power of the stars), an ens naturale, spirituale, venerd, etc., as factors in life and disease. 14 History of Pathology. observation, physiological experimentation and anatomical dissec- tion grew more and more toward a plane of real excellence, af- fording an increasing clearness of insight into the processes which obtain in both healthy and diseased bodies. The anatomical changes shown in necropsies directed attention to the topography of disease. Morgagni (1682-1771). a teacher of anatomy in Padua, in his work, "Dc Scdibus ct Causis Morbontin" (1761), outlined the first comprehensive and system.itic exposition in this direction and came to be regarded as the founder of pathological anatomy. From efforts to correlate manifestations of disease of the various organs with the presence of anatomical changes, arose the school of Pathological-anatomical Diagnosis, to which is due the discovery of a number of valuable methods of diagnosis (per- cussion, thermometry, the microscope, chemical analysis), and which had as its founders men like Bichat, Pinel, Corvisart, Dupuytren, Auenbriigger, Laennec and Rokitansky. The advances in physiology inaugurated bv Johannes Miiller (1801-1858) and the cellular theory formulated by Th. Schwann, along with the development of microscopic anatomy, are respon- sible for an important change from the older conceptions of dis- ease, giving us as a basis for our ideas of morbid processes a cellular pathology, first proposed by Rudolph Virchow (1858), who referred the real seat of disease to the individual cells and the tissues, and regarded disease as depending upon the reaction of these to harmful influences. Although it is but about fifty years ago that Schonlein's school looked on disease as some sort of living thing of extra-corporeal origin, entering the bodies of men and animals like a parasite and expelled by our therapeutic measures ; yet in the interim the study of Aitiology has developed the definite view that disease is but the manifestation of mor- phological, chemical and functional changes which are induced by the most varied harmful influences upon the cells and tissues, chemical or physical ; and thus to-day, through uniform and ex- act methods of objective research, clear conceptions and positive knowledge are in hand relative to most diseases. As far as comparative pathology is concerned, it too was com- pletely dormant from the fourth until the eighteenth century, at first because of the general depression in science, later because medical practitioners had but little interest in the diseases of ani- mals when human medicine was developing along these newer lines, but especially because of the aversion which men came to Comparative Pathology. 15 hold for even mere contact with the dead bodies of animals. Among the rare publications appearing in the middle ages there is onlv one large work on the anatomy of the horse (issued in 1598 by the \'enetian senator, Carlo Ruini, but probably the product of some physician) which is at all worthy of note as showing any advance in knowledge. At the same time the nat- ural history of the domestic animals was considerably advanced by C. Gessner (15 16-1565) and Aldrovandi (1522- 1605). Prac- tice of veterinary medicine w^as relegated more and more to far- riers, executioners and butchers and naturally drifted into the crudest sort of empiricism. However, when skill in riding and horses became more prized in the courts of princes and in war, there was a change for the better; and Italian, French and Ger- man masters of the stable (Pignatelli, J\Iarx Fugger, Bohme, Winter von Adlersfliigel, Robertson, J. von Sind, Solleysel, Pluvi- nel. Lafosse) published a number of works upon the diseases of the horse. From the eighteenth century physicians once more be- gan to frequently pay attention to animal pathology; the necessi- ties arising from devastating epidemics among cattle, particularly cattle plague, stimulating the members of the medical faculties to endeavor to stamp out these diseases and to publish numerous articles upon investigations bearing in this direction (Ramazzini, Lancisi, Schroeck, Golike, Kamper, Sauvages, von Haller, Paulet). In the years from 1762- 1790, in most of the [European] states, schools of veterinary medicine were established, the first being inaugurated by Bourgelat in Lyons and Alfort. With this step comparative medicine found a place in scientific institutions, later, after various changes in organization, assuming the rank of independent colleges or becoming incorporated with the universi- ties. The first teachers of veterinary medicine were for the most part physicians ; and even to the present the progress of the sci- ence is in close sympathy and relation with human medicine. However, the men who in the nineteenth century have been edu- cated to the dignity of independent investigators and to a new standard as veterinarians, have broadened comparative medicine to a manv sided field ; and the results of their discoveries and their practical achievements have become of importance not only to the farming and cattle-raising industries, but to the general wel- fare of mankind as well when one takes into consideration the consumption of meat and the dangers of animal epidemics. PREDISPOSITION TOWARD DISEASE Any living being becomes affected by disease when no longer able to adapt itself to its environment and to the demands to which the functional ability of its cells and organs is subjected. As soon as such external influences exceed the limits of endur- ance, as soon as they so affect the cells and organs as to induce alteration of function, they become causes of disease. There is really nothing upon which the animal body is dependent or with which it is related, but may on occasion cause the onset of disease — nutrimient, air, light, temperature, the various animal and vegetable organisms about it. the varied accidents of nature, its own active and passive relations, as well as every physiological process going on in its economy ; and the very same factors, which are generally essential for the maintenance of existence and the well-being of the individual, may become agencies of harm and noxious {nocere, to harm) influences productive of disease. Whether the individual should experience the harmful possi- bilities of such factors or not depends upon the inherited po- tentiality of the organism, the functional capabilities of its cells and tissues, and upon the efificiency of its protective and reg- ulative mechanism. Sensitiveness to noxious influences, known as Predisposition, and insensitiveness or insusceptibility, commonly spoken of under the terms Resistance or Immunity, are by nature widely different among different species and individuals and even among the different tissues in the same animal ; and are subject to considerable variations and abnormalities. The polar bear, the Esquimau dog and the reindeer are accustomed to the cold of the north, but sicken in the temperature of warmer climes ; many ani- mals thoroughly adapted to the tropics, perish when transferred to cooler regions even though furnished with their usual food. Indi- vidual animals of the same species often manifest differences of susceptibility, as where in herds of cattle or even, as is often ob- served, in a number of cattle kept in the same stable, some path- Variations in Predisposition. 17 ogenic influence equally operative upon the whole group fails to pcoduce its effect upon all, certain individuals resisting it suc- cessfully ; or it is often noticed that here and there an animal sickens under conditions quite favorable for most of its species. The difference between different tissues in predisposition and im- munity may be seen in comparing the skin and mucous mem- branes. The surface of the skin, with its hard epithelial cover- ing, is much less sensitive to irritative substances than are the delicate mucous membranes ; the mucous membrane of the stom- ach in the living animal is resistant to the action of acids, but that of the lower end of the intestinal tract may be injured by the acid of the gastric juice. A number of poisons (snake venom, tetanus toxine) are en- tirely harmless when taken into the alimentary canal ; although, if introduced by way of lesions of the skin into the tissues, they are extremely pathogenic. Especial interest attaches to the differences in predisposition and immunity toward the viruses of infectious diseases. In all infectious diseases we have to deal with poisonous materials caused by micro-organisms. These micro-organisms (micro- phytes, vegetable microscopic organisms ; fnicro.coa, animal micro- scopic organisms) gain entrance to the body by alimentation, or by the respiratory path, or through ivounds, or may even actively penetrate the tissues should they be in close relation with the skin or mucous surfaces. Within the body structure they mul- tiply for a time and work harm to the tissues chiefly by the specific poisons existing in their protoplasm (that is, in the bodies of the microbes) or by poisons elaborated by them, diffused in the tissues and taken up by the blood. In the contest waged with these microscopic foreign invaders a twofold task is set for the animal body ; it must in the first place destroy the microbes and at the same time must render their toxines inert. One ani- mal may accomplish this with ease ; another with difliiculty. Some species of animals are by nature uninfluenced by the toxine of an infection which is sure to produce disease in another species ; thus cattle are immune to glanders, the horse to pulmonary tuberculosis, and chickens bear large doses of tetanus toxine with- out injury to health. Such absence of reaction to infections and their toxines in an animal species is spoken of as natural immunity. It is to be explained from one standpoint by the idea that the cells and tis- i8 Predisposition and Immunity. sues of the immune animal have no affinity^ or but little affinity (chemical affinity), toivard the toxines of the infection. The poisonous elements simply do not enter into combination with them. For example, the nervous system of the turtle is absolutely immune to the toxines of diphtheria and tetanus, and these sub- stances may be injected into the animal entirely without effect. Yet the toxines thus introduced may remain in the bodies of the experiment animals for months without being rendered inert by the juices ; and should the blood of such a turtle be injected into some susceptible animal it will act in the sarne manner upon the latter as would the toxine itself, FYom a second point of view it is to be recognized that im- munity may depend upon the fact that some of the cells of the animal in question are able to take up and digest micro-organisms, and thus render them harmless (Phagocytosis). This power of seizing and ingesting small particles, organic and inorganic, or dead and living cells, is peculiar especially to the motile types of leucocytes (wandering cells, white blood cells), but is also possessed by giant cells, splenic and medullary cells, and even fixed connective tissue cells (as endothelium) ; and plays an important part in the economy of the body. Its significance has been pointefl out especially by the ingenious investigations of Metschnikoff, Leber, and Bordet. These phagocytes act as scaven- gers, taking up and making awa}' sometimes with blood debris, nuclear fragments, pigment, fat globules and all sorts of minute foreign particles with which they come in contact. The ingestion of such corpuscular elements is with them a simple process of feeding. The movement and approach of the phagocytes may be induced bv a number of stimuli, as warmth or an acid, acting upon their own tactile or chemical sensitiveness. Tn coming in contact with foreign particles they attempt to increase their surface of contact as much as possible [applying their protoplasm more and more about the surface of the particle, and thus eventually enveloping it in their own material] ; and are at- tracted by various chemical substances (cheniota.vis) . [It is but fair to add here that while the theory of chemotaxis, as a part of the general theory of "tropisms" or of blind automaton- like response of living things to external forces or attractions, finds wide adherence among medical men and biologists, there are nevertheless others who do not accept such a view, the latter finding reason to believe that the manifestations which the former Protective Substances. 19 school attribute solely to non-intelligent attraction from without are really due to an inherent power of a low intelligent char- acter of the organisms showing them. These latter would attribute even to individual cells as the phagocytes, a low but 1^ actual volitional power to either originate or refrain from efiforts to approach the foreign particles referred to.] The proto- plasm of the phagocytes apparently can secrete digestive juices [there is reason to think that certain granules seen in leucocytes are of the nature of ferments], through the action of which they are able to assimilate nutritive matter and dissolve foreign bodies. In this latter manner, in part at least, it is possible that the virus of infectious diseases may be removed from the tissues. Nuttall first pointed out that in the blood plasma of healthy ani- mals there exist certain substances which are capable of dissolv- ing the body matter of bacteria, and of thus destroying them. These substances, called alexins by Buchner, and complements by Ehrlich (by others addimoifs and cyfoscs), are products of the cells, which are either given off by the living cells (Buchner) or are set free by cellular destruction (Metschnikofif) ; and are found in varying amount in the circulating blood of the indi- vidual animals. An excellent example of these substances is seen in the efifect, discovered by Behring, of the serum of white rats upon the anthrax bacillus. If hundreds of thousands of anthrax germs are placed in some serum from a white rat (at 37° C.) it will be noticed after ten or fifteen minutes that the bacilli have become swollen and degenerated (granular), and after from four to seven hours that they have completel}' dis- appeared. Canine or ovine serum does not possess this power, but should a few drops of rats' serum be added to sheep, serum the bactericidal action will immediately appear. The serum of the horse also has a strong bactericidal power. It must be clear that the cause of natural immunity cannot be attributed to the bactericidal action of the serum alone, for both rats and horses are susceptible to anthrax ; it must be thought of, as already men- tioned, as dependent in part upon the lack of affinity of the living cells for the toxines of the infection, and in part upon their phagocytic power. Just as among different animal species and individuals there may be some one kind which is more highly resistant to poisons than the rest, so there may be met others exhibiting an excessive susceptibility to such 20 Predisposition and Immunity. influences. For example, cats are extremely sensitive to carbolic acid. It is well known that some persons possess so marked a susceptibility tc a number of substances and foods (as strawberries, mushrooms, crabs, lobsters, cocoa or alcohol) that after partaking of them they experience severe pain, vomiting and cutaneous eruptions, and in the same way are apt to be severely affected by certain medicaments (chloroform or mor- phine) ; they are influenced by such substances, as it were by poisons. Such extreme susceptibility is known as idiosyncrasy (i'Sios, •peculiar; i] ffvyKpd(ns, combination). As a rule, the predisposition or inimiiinty of individuals is only a relative one ; that is, it is variable and of moderate degree, may be increased or decreased, and is often only temporary. Racial or specific immunity may also be but relative. Rabbits are ordinarily immune to symptomatic anthrax, but now and ?gain a rabbit is found to be susceptible to this disease upon inoculation. Goats, horses and cattle are strongly resistant to swine-erysipelas, but if large amounts of the virus are injected intravenously they may show severe symptoms. Young dogs are somewhat susceptible to anthrax ; older dogs less so. Young sucking calves are very rarely afifected by "black leg" and usually resist inoculation tolerably well ; but as soon as they begin to eat vegetable food they become very susceptible to the disease in question. Thus age and food are seen to have an influence upon predisposition and immunity. How intimately connected 'the latter factor is may be inferred from the experiment, origi- nally performed by Feser and afterward confirmed by others, in which rats, if fed upon meat alone, are found as a rule to be immune to anthrax, while if fed on bread they soon succumb to inoculation with the virus. By experimentation it has been shown, moreover, that hunger is a predisposing cause, that bodily overexertion (overheated ani- mals), nutrition of restricted quality and excessive amount ( as a diet too rich in fat) may have such depre'ssing influence that animals subjected to them' readily succumb to injurious agencies which they would otherwise bear, and particularly become less resistant to infections. It is also true that certain, altered condi- tions of the tissues afford especially vulnerable points for the attack of pathogenic influences ; for example, gastric catarrhs, by diminishing the production of hydrochloric acid, favor the deposition and pathogenic action of bacteria which are otherwise destroyed by the gastric juice. As a rule, previous disease leaves as a sequel an increased disposition, the formerly affected tissues Acquired Predisposition and Innnunify. 21 sliowing a diminished resistive power for a long time {local pre- disposition; locus ininoris resistenticc), as, for example, mucous membranes after catarrhs. Predisposition to disease and (a ^natter of extreme impor- tance) immunity against disease may he acquired. It is well known that recovery from certain infectious diseases is accom- panied by an insusceptibility to a repetition of the same affection. This immujiity after previous attacks is at times only temporary, but a few weeks or months in duration, or it may extend over many years or for the entire lifetime. The alteration which has taken place in the condition of the body in such cases is chiefly a chemico-biological one, and although much remains enigmatical concerning it, some insight into the process has been obtained through experimental investigation. Besides the discoveries of Jenner and Pasteur, who gave to mankind facts and methods of the highest importance toward succe^ in combating infections, by which it has become possible by artificial inoculation of an attenuated virus to produce a mild course of the infection and to obtain therefrom immvmity from subsequent attacks of the same disease, there must also be recalled the important discovery that in the blood of man and animals, after attacks of infections, there appear certain substances which are of specific anti-toxic char- acter and are destructive to the virus, and that upon the produc- tion of these substances depend protection and recovery from these diseases. The tissues of the animal body react to irritants which gain access to them. Should a particle of dust or a gnat happen to lodge upon the conjunctiva, such a foreign body acts as a stimulant to the nerves of the mucous membrane, this inducing a free secretion of tears, which usually wash away or dissolve the object. In an analogous manner there is a reaction on the part of the tissues should a toxine or some pathogenic germ (virus, bacterium) come into contact with them, not in this case with a simple secretion to wash away the poison, but nevertheless re- straining the poison and giving origin to substances which are apparently actual antitoxines, or which are able to destroy and thus render harmless the germs of disease. The conditions un- derlying the production of such antagonistic or protective sub- stances, t^eir mode of origin, manner of action and properties, are of extremely complex nature. The numerous experiments of such investigators as Behring, Ehrlich, Brieger, Kitasato, Wassermann, Buchner, Emmerich, Fodor, Nuttall, Nirssen, Bordet, Morgenroth 22 Predisposition and Immunity. and Sachs, have, however, brought forward facts hitherto unsus- pected and of the greatest interest in this connection, and have pointed out not merely theoretical hypotheses upon immunity, but also practical methods of extreme value in combating the in- fectious diseases. As already pointed out, there already pre-exist in the normal blood of every animal certain substances capable of dissolving foreign material which has in some way gained entrance, and, by entering into combination with resultant toxic matter, of render- ing it harmless. In some of the glands, as the thyroid and liver, neutralization of toxic matter and noxious metabolic products is being continually carried on ; and when one considers the innu- merable reactions ;and interactions which are taking place in metabolism, resulting in the most varied types of secretory ma- terial with destructive and digestive properties, it is easy to think of the body and each of its cells as a chemical laboratory of manifold productive ability. In attempting an explanation of the m.echanism involved in the production of these antibodies (antagonistic or protective substances), Ehrlich has proposed a brilliant, and, at first thought, a very convincing theory, the chief points of which are briefly included in the following. The hypothetical details of this theory have recently met such serious objection at the hands of Gruber that in a great measure it seems but doubtfully credible. The basic fact that antitoxines and protective substances are products of the cells and organs of the body is not endangered by this criticism, but the problem of how and where such substances are formed is renewed as a matter for further investigation. According to this view the cells of the body may be thought of as organisms which consist of a basis of protoplasm, which has as its vital center a nucleus (vital nucleus of Ehrlich) ; this protoplasmic unit may be fancied as being possessed about its periphery of armlike processes, the receptors or side-chains of Ehrlich. [It is to be understood here that the author refers to the protoplasmic molecules as the basis of this theory, each mole- cule being composed of a more or less complex group of atoms or of combinations of atoms. The vital center does not refer to the nucleus seen as a structural part of the cell, but to the struc- tural nucleus of such a complex molecule of its protoplasm. As is attempted in the graphic chemical formula of a complex or- ganic molecule with the symbol C as its center, to indicate as Ehrlich's Theory of I in in unity. 23 "side-chains'' the various atoms or groups of atoms linked about this nucleus, so in Ehrlich's view the living proto- plasmic molecule may be thought of as having as its elemental or basic compound a vital nucleus about which are attached, and probably from which spring, a number of other atomic groups subsidiary to the center of the molecule and corresponding to the side-chains of the formula, but essential to the efficiency and integrity of the whole complex molecule, since they are its means of combination. These are the receptors or haptophores of the molecule. Every molecule possesses these haptophores in addition to its principal part, the centre or nucleus (in living protoplasmic molecules, the vital centre). Should these haptophores be lost in the living molecule, they are replaceable by others of like type because of the vital regenerative power of the molecule.] The receptors are the principal instruments of [molecular, or in other words] intracellular metabolism and provide nutri- tive substance to the cells through their ability to unite chemic- ally with such material. However, just as proper food elements may thus combine, so other albuminous bodies or materials chem- ically allied to foods become linked to or combined with the receptors, as material extracted from bacteria, various poisons of animal, bacterial and vegetable origin (toxines, venom of bees, spiders or snakes, diphtheria toxine, ricin, abrin, the substance of blood cells, spermatozoa and nervous tissue, and the milk albumen of different kinds of animals). Such union occurs be- cause these substances contain in their molecular composition certain groups of atoms, which, like similar atomic groups in foods, have an affinity (chemical affinity) for the atomic groups of the cellular protoplasm ; these Ehrlich speaks of as their haptophore groups. [Thus both the protoplasmic molecules of the body cells are provided with haptophores or combining chains, and, too, all nutritive or harmful molecules which come in con- tact with them. Should there be affinity between the haptophores of the cellular protoplasm and those of the introduced molecules a combination will result.] With such combination effected [the molecule and in proportionate degree the whole] cell comes under the influence of the substance chained to it. Should the latter possess properties actively harmful to the protoplasm, poisonous qualities (toxophorc) , the cellular protoplasm becomes more or less injured, and a pathological cellular lesion results. There may ensue complete death of the cell [protoplasm], 24 Predisposition and Immunity. or merely a condition of irritability or partial injury. If the injury be partial tliat part of the cell [protoplasmic molecule] which remains sound restores the defect. In this condition of irri- tability or stimulation there is a reaction on the part of the cellular protoplasm left with its vital centre intact to regenerate the receptors destroyed by the toxic influence. Following a law recognized by Weigert, regeneration in the cells of an organism is usually productive of more of the substance than originally ex- isted at the site of loss ; and so here the restoration is often so active that an excessive number of receptors are supplied to replace those which have been destroyed. "Such an excess of receptors constitutes a useless ballast for the cells and the extra ones are thrown out into the blood and circulate therein" (Ehr- lich, Wechsberg). The presence of these free receptors in the blood, representing haptophores or chemically combining sub- stances, affords opportunity for materials which have gotten into the blood and which have chemical affinity for them, having come in contact, to enter into* combination with the receptors. Thus held by these free receptors, such substances are prevented from involving the cellular protoplasm, and as a result the cells and the whole individual are protected from the disease. This power of molecular combination differs in the different cells of the same individual and in the cells of different species of individuals. One species may possess no cells containing the elements essential for combining with a certain toxine; there would then be absolutely no chemical affinity shown between the cellular molecules and the toxic molecules, and a priori the latter must be without effect. In such a case the toxine, perhaps in large quantities, may remain for weeks in the blood and general circulation without any harm resulting to the individual. Such instances are examples of natural immunity. On the other hand, an individual may possess a vast number of receptors not merely in the general body, but each cell, each corpuscle, for example, may contain a mass of material capable of combining with sub- stances of one or other kind. In classification of these receptors it is customary, following Ehrlich, to distinguish them as of I, II, III, etc., orders. The first order (unieeptors) includes receptors having only one haptophore group for poisons (toxines) and utilizing this for combination with such substances ; they are called antitoxines. The presence and formation of antitoxines is illustrated by the Lysiiis. 25 immunity to toxines acquired after infectious disease. The tox- ines are allied to the albumens* and enter the blood in a state of solution ; thus dissolved, they here enter into combination and are therefore inert before they gain access to the tissues, as the nerv- ous tissues — the cells (bacteria) which give origin to the toxines being removed from the economy by phagocytosis (as tetanus or diphtheria bacilli). Another class of receptors [III order of Ehrlich] has the power of combining with foreign cellular elements and at the same time drawing into the combination the ferment-like alexines which naturally have pre-existed in the blood ; these thus must possess two haptophore groups (a cytophile and a complementophile group), and for this reason are known as amboceptors. For this element which is the medium (amboceptor) of the chemical union (anchoring together) the following terms are also employed: dcsiiwji (se'w := I bind), immune body, intermediary body, copula, immunisin, fi.vateur, sensitising body. The alexine is also known as the complement, addiment and cytosc. \\'hen by the combined action of these two elements the destruction and solution of foreign cellular elements (the toxine- producing animal and vegetable microorganisms themselves) are accomplished, the compound antibody [amboceptor and comple- ment] is spoken of as a cytolysin (E. S. London). The presence of the two elements allied to each other is shown by experiment. If one will heat a serum containing cytolysins to 56° C. the complemental element will be destroyed, and the serum will be fovmd to have lost its cytohtic power, is inert. If, however, to this serum there be added another, ordinary serum, containing only complement and inert by itself, the cytolytic power is restored to the first, and it is said to have been reactivated. So, too, the desmon or amboceptor in the c}i;olysin may be removed by adding to serum cells for which it has affinity [and by centrifugation these may be thrown down : while the serum continues to contain the complement] . There are a number of cytolysins of different kinds, each exerting its influence as a rule upon only one certain kind of cell [this depending upon the peculiar affinity of the amboceptor in the cvtolvsin combination] : thus we recognize amongf manv those which act upon red blood cells (hccmolysins) , upon sperma- ♦Poisons of other types, alkaloids, glucosldes. saponines, which do not act by forming chemical combination do not cause the formation of antitoxines In the organism. (Ehrlich, H. Sachs.) « 26 Predisposition and Immunity. tozoa (spermolysins) , upon bacteria (bacteriolysins) , upon white blood cells (leucolysins). Some dissolve several kinds of cells, as in the case of spermolysins, which destroy red blood cells as well as spermatozoa. From this it may be seen that in general cytolysins possess specificity of action. The appearance of cytolysins in the body of any given animal is occasioned by the introduction of cells of a different species of animal into the first. If human blood be injected in increasing amounts under the skin of a rabbit or into its peritoneum, the serum of the rabbit will acquire the power of dissolving the hu- man red blood cells, but not those of horses, cattle or guinea-pigs. If the spermatic fluid of guinea-pigs be introduced into rabbits, in the same way the serum of rabbits becomes solvent for the spermatozoa of guinea-pigs, but cannot influence the spermatozoa of another species of animal. If colon bacilli be injected into an animal a cytolysin will be developed destructive only to these microphytes, and in fact only to the particular strain of this bacterial group which was employed in the experiment. From the foregoing it should be reahzed that the principal feature in the production of immunity against foreign celhtlar elements is the formation of the amboceptor or desmon, and that this alone is a new product of the cells of the invaded body ; the other element, the alexine, naturally pre-exists in every body, its combination with the desmon form- ing the cytolysin. If, however, the necessary alexine be absent or present in insufficient amount, the C3'tolysin will not appear. In this latter way must be explained such occurrences as where, in spite of repeated introduction into an animal of some type of cells, the blood acquires no cytolytic power, but where on further addition of the serum (containing the required alex- ine) from another species of animal cytolytic activity is immediately produced. The sources of the amboceptors are apparently the bone- marrow, spleen, lymph glands and perhaps the subcutaneous con- nective tissues. In addition to the production of antitoxic and cytolytic sub- stances the body may engage along the same line of reaction in the formation of substances [II order of Ehrlich] which cause foreign cells to aggregate in masses (clumping, agglutina- tion), the so-called Agglutinins; and other substances which coagulate foreign types of albumens (Coagulins) and cause their precipitation (Precipitins). In illustration, if defibrinated human blood be injected into a rabbit there is developed in the blood of the latter a substance which will act on human blood to Post-Infections Immunity. 27 cause a flocculent precipitate. Init which will not (as a rule, and never if certain m(3des of application are employed) exhibit such precipitating^ qualities with any other type of blood. It is inter- esting in this connection to add that the serum of a rabbit so treated will also precipitate the blood of anthropoid apes, gorillas, orang-outangs and chimpanzees, thus indicating a relationship of these animals to man. Cytolysins and haemolysins also serve to show the relationships existing between animals in the zoological system of classification. Inasmuch as this reaction is applicable as well with a solution of old and dried blood, the discovery (which as an outcome of research in the field of immunity is due particularly to Bordet, Ehrlich and Morgenroth) has acquired especial importance as a means of information concerning the source of blood stains in forensic medicine. Other albumens may also lead to the formation of specific antibodies in the animal organism, as milk albumen ; thus by subcutaneous injection of goat's milk into rabbits, horses or cows a serum may be obtained which wilt immediately cause a precipi- tate if it be added to goat's milk. In the same way, by inocula- tion, coagulins may be obtained for cow's milk. In the same way, too, in the course of an infectious disease a series of substances are produced in the human or ani- mal organism which render the infectious matter for the time harmless. Should the infectious products develop very rapidly, and by their poisonous properties cause serious protoplasmic changes in the bodv cells, the disturbance is apt not to be limited or checked, and in spite of any reactive-products which may be formed the function of the cells becomes altered and the animal dies. Should the [protoplasmic molecules of these] cells be only partly injured the body prevails over the disease, the molecular defects of the cells becoming regenerated. The surplus of anti- bodies, the result of this regenerative action, are after recovery found circulating in the blood, and in some instances may even pass into the milk. The amount of protective bodies or anti- bodies in the body-fluids varies according to the intensitv of the reaction and the time elapsed after recovery from the infection, the greater part being used up during the course of the disease and the remaining gradually disappearing in metabolism ; while with the removal of the stimulus the supply from the cells tends to cease. If, however, infectious and toxic material be again introduced into the system, stimulating and injuring the cellular 28 Predisposition and Immunity. protoplasm, the production of antibodies will be again induced, receptors being again formed. This form of immunity, produced through cellular activity following the introduction of the infec- tious agents, is known as "'active immunization." The discovery of the existence and production of specific antibodies in the serum, for which we are mainly indebted to the studies of Behring upon tetanus- and diphtheria-immunity, has led to extremely im- portant methods of prophylactic and therapeutic inoculation against a number of the infectious diseases. This becomes possible from the fact that the blood* serum of an animal which has survived a certain infection and is highly immunized against it can be em- ployed by injection to produce in a second animal similar im- munity against the same disease. The production of the pro- tective material in the blood depends upon the introduction into the experiment animals, either intravenously or subcutaneously, of gradually increasing amounts of the infectious material against which immunization is sought. The animals in this way become more and more highly immunized and their blood serum becomes correspondingly rich in antitoxine. By such a system of pro- gressive inoculation it is possible to attain a degree of concentra- tion in which a thimbleful of the serum contains more immuniz- ing material than would exist in all the blood of the body after one single attack of the disease. The ability to produce such materials exists in the cells of all kinds of animals, both those susceptible to the disease in question and those naturally resistant to it. For example, by injecting the bacilli of swine-erysipelas, which in natural conditions are pathogenic only to the bristled kine, it is possible to induce the reaction also in sheep, goats, cattle and horses and produce in their blood immunizing substances ; and then, after withdrawal of the blood from animals thus pre- pared, to obtain from it a prophylactic and curative serum in suffi- cient quantity for use in hogs. The production of active im- munity in an individual requires some time, because the body cells must first form the protective substances ; in other words, must first pass through the period of the disease, perhaps four to six weeks in duration. \A'hen, however, the prepared serum is intro- duced there is no such demand placed on the body cells ; the pro- tective substances, already formed, produced from the animal supplying the serum are introduced into the second animal. An immunity thus obtained is spoken of as "passive immunity." It comes on immediately or in a few hours after the inoculation. Protective Immunization. 29 according to circumstances. As a definite cellular reaction in such a case does not occur at all, or at best only in a minor degree, and as the amount of protective antitoxic material intro- duced is gradually used up, destroyed or excreted , (urine) and no new antitoxine is afforded because of lack of proper reaction, such passive immunity passes away after a short time (seven to fourteen days). The recognition of this peculiarity has in practical application led to , the coincident or successive employment of both methods of immunization in case of certain of the infectious diseases. Serum is first injected so as to induce a passive immunity in an animal, and living germs are next inoculated so as to transfer a passive into an active immunity ; the previous introduction of the protective serum making the later inoculation with living microbes practically free from danger. CONGENITAL AND INHERITED DISEASES If there exist at time of birth in an individual actual disease, or peculiarities of predisposition or immunity which also char- acterized the parents or ancestors, such conditions are said to be congenital (innate), and in the latter instance inherited (heredi- tary) as well. The genesis of such an occurrence is by no means always the same, although in a measure it is apparently dependent upon conditions of the parents. During intrauterine life the embryo may experience injuries affecting its normal growth, causing deformity, interfering with the proper development of a limb or organ, or destroying some part already in stage of development. Such injuries are for the most part mechanical in type, as where amniotic adhesions (or more rarely tumors of the uterus) by constriction or pressure of this or that part of the foetus (which in its movements might be entangled in the amnion) may compress, wound or otherwise injure it. Depending on the nature of such an injury, the embryo may in consequence present gross or trivial faults of one sort or another; these are spoken of as foetal or emhryogenous anomalies, Z'itia congenita, developmental defects or monstrosities. Except when a uterine lesion is the cause of the deformation of the foetus, the mother has no influence upon the production of anomalies in the offspring. There are a number of infectious diseases whose causative micro-organisms are capable of gaining access to the foetus indi- rectly through the placenta. In .their multiplication in the pla- cental tissue they may, by growth, penetrate it and obtain entrance to the blood of , the foetal side. Under such circumstances the newly born animal carries into the world with it the same disease from which the maternal parent was sufferinig during the term of her pregnancy; the acquirement is here placental. The most com- mon example , of such a transmission is seen in congenital tuber- culosis in cattle, occurring only in case the cow has uterine tuber- 'culosis. The congenital pathological conditions of this type have Congenital Predisposition. 31 therefore an intrauterine mode of origin, which, if strictly niter- preted, is comparable to acquirement by an external influence, only tliat in this instance it operates within the womb. It is reasonable to believe that injurious metabolic products which pass through the placenta of a mother animal suffering from some febrile condition (especially metabolic and nutritive disturbances which react from the mother upon the embryo, affecting primarily the ovum, or in the father's case affecting the spermatozoon in a similar manner) occasion morbid predisposi- tions, as diminished developmental energy, or perhaps a tendency to excessive growth (dwarfism, fcetal chondrodystrophy, gigan- tism), weak metabolic power, tendency to fatty degeneration or fatty deposition {ovo genie or spermatogenie predisposition, con- genital degenerative inheritance). According to Weissmann and Ziegler, it is quite probable that often predisposition to disease and congenital pathological char- acteristics are due to germinal variations; that is, that when two unadapted sexual cells unite there may be developed to some de- gree new and perhaps even abnormal peculiarities in the embryo from the union of the two elements (amphimixis of the ovum and spermatozoon). Thus healthy, strongly-constituted parents may often be seen who sometimes beget offspring of feeble constitution, weak-minded or of other morbid tendency. The off'spring is never entirely like either parent, and the various members of the same generation are never alike in bodily struc- ture and character. Only in case of twins, developing from one ovum or from one act of copulation, is there striking similarity of the bodily features. In the mingling of the maternal and paternal sexual elements two strains of hereditary tendency unite to pro- duce new germinal variations. Should there be thus produced new peculiarities of value to the individual, or which we care to preserve, type-characteristics (precocity), these are not regarded as pathological ; but it is readily conceivable that the variations might but poorly fit the off'spring for life and render it but feebly resistant to given pathogenic influences or show from the first abnormal constitution of its tissues. In such cases is presented a germinative or constitutional predisposition. A predisposition, no matter how developed, as well as ac- quired immunity, may be transmitted to the offspring, provided the individual is capable of begetting; yet not every tendency toward disease and not all the resistive powers of the parent are 32 Heredity. necessarily continued to succeeding generations. Only such con- ditions are transmitted as pre-existed in the germ, in the seg- mentation cells and the embryo, or those in which apparently the nature of the whole parental cellular structure is altered, as germinal variations and so-called constitutional tendencies and diseases. Injuries and diseases which do not involve the sexual cells, as all simple traumatic lesions of the body, give rise to no trans- mission. For example, the common custom of cropping the ears and tails of dogs has never led to the birth of a short-eared or stub-tailed dog or of such a breed (just as the practice of cir- cumcision, practiced for hundreds of years among various peo- ple^ has never yet caused any congenital anomalies of the prepuce). If occasionally structural anomalies of this type are encountered careful investigation will show that some intrauterine mechanical fault is responsible for the defect in the foetus, as Bonnet has demonstrated in case of stump-tailed dogs that the caudal vertebrae have been bent or deformed simply by intra- uterine pressure (amnion). This is also proved by the fact that the same anomaly occurs in cats (and in any other animals whose tails are unobjectionable to man and for the removal of which there is no occasion), showing that the habit of cropping can scarcely be held responsible. Non-transmissible conditions and those which are truly in- herited may very closely resemble each other in their anatomical features, and yet depend on entirely different causes ; only the closest inquiry revealing the fundamental influences producing them. For example, supernumerary toes (polydactylism) may be an atavistic phenomenon, a. family trait, or may occur in a foetus as a splitting of a digit because of amniotic adhesions ; in the same way harelip (congenital fissure of the Ijp) may be caused by local amniotic trauma or may be an hereditary anomaly. Heredity is best understood when it concerns chemical in- Hucnces. As indicated by Ribbert, it may be conceived that the whole bodv can suffer from the wide dissemination through it of some chemical substance and that, of course, under the circum- stances the germ cell is also reached by the same noxious ma- terial. If the organism survive such disturbance and become immune through the changes called forth by the chemical poison, the germ cell may also survive with the same iniinitiuciiig changes. Should such a process befall both parents, both spermatozoon Hereditary Disease. ' 33 and ovum are likely to be imnuine and the new cellular structure resulting from the copulation of these two (the embryo) will possess the same characteristic and transmit it again, because its own sexual cells are clearly the descendants of the rest of the group. In the same way a predisposition may be established and transmitted, because the chemical substance in some way weakens the germ cell and diminishes its resistive ability, and by the fusion of two similarly enfeebled sexual cells the progeny, as the product of both, partakes of their equalities. Similarly to such chemical influence as Ribbert suggests, any exaggeration or diminution of the body temperature must affect the germ cells. Inherited pathological conditions and properties of immunity need not necessarily manifest themselves in each successive gen- eration of posterity indefinitely; for the most part they are limited to a few generations and then disappear. But they may recur in later generations. If but one of the progenitors possess a certain predisposition and come in sexual union with a non- predisposed individual, the pathological condition will progress- ively diminish by half (Ribbert) because of its distribution in the two sexual cells ; is proportionately corrected by the healthy cell of the copulation and by germinal variation ; and grows weaker and weaker until it is no longer a factor in the posterity. Should the peculiarity reappear after several intervening genera- tions, it may be assumed that this occurs as a result of the union of two germ cells, each possessed beforehand of a disposition which was hitherto latent, but which from the summation of the characteristics of both parent cells has again become sufficientlv intensified to reappear as a pathological fault (Ribbert). Hence we distinguish: a direct li credit y from father and mother to the oiT- spring; a latent heredity if the offspring of affected parents are spared but in the next or later generations the disease should appear, arising from a transmitted tendency ; a collateral heredity, should the disease manifest itself in the side lines of the family group ; an atavistic heredity, when the origin of the disease suggests a reversion to the family ancestry. In human medical practice the following are considered as diseases transmissible by heredity: Hsemophilia or hsemorrhagic diathesis, color blindness or Daltonism (so named after the Englishman, Dalton, who was himself color-blind), lenticular opacity or "gray cataract" (or cataract), near-sightedness or 34 Heredity. myopia, pigment-atrophy of the retina, polyuria (production of excessive amounts of urine), predisposition to mental diseases, to progressive muscular atrophy, to tumors, to obesity and to cer- tain malformations (dwarfism, polydactylism, harelip, etc.). The anomalous conditions mentioned are due, perhaps, to germinal variations, possibly first brought into active manifestation by the introduction of some external disturbing factor. (Vide Rib- bert, Lehrbn'ch der all gem. Pathologie. 1901.) What parts respectively are taken by heredity and by external influences in the development of congenital affections is in many instances difficult or even impossible to determine, as our knowl- edge of these matters is still deficient. This is particularly true regarding the so-called hereditary defects of the domestic animals. Among the diseases included in this category for the last century or more, some are surely not inherited and not transmissible but occur because of external influences ; for example, intermittent ophthalmia, cataract, asthma, ringbone, frog-thrush. Others, as dumb-staggers ["blind-staggers"], hsemoglobinsemia, curb, spavin, deficient hoof-formation, may be caused directly by external in- fluences, although it cannot be denied that inherited structural de- fects may indirectly favor their appearance.* As instances of direct inheritance and congenital origin may be mentioned many cases of goitre in animals. *Cf. Dleckerhoff. Veher d. Erhfehler hei Zuchtpferden: Zcitschr. f. Vctcrinar- hunde, 1902, Feb., p. 53. CAUSES OF DISEASE The influences Avhich lead to bodily injury, to pathological lesions, and which are spoken of collectively as disease causes (causer uwrhi) may be arranged in a number of classes. There are influences dgainst which the strongest and most resistive constitution is powerless and which inevitably induce disease in the animal coming under their action ; such absolute pathogenic influences include mechanical forces, intense thermic and electric agencies, mineral and vegetable poisons in their higher dosage and concentration, and, provided they can gain entrance to the intracorporeal structures, various animal para- sites, bacteria and [animal] microorganisms. Other harmful agencies are pathogenic only under special circumstances and are therefore only relative, depending, for example, on the quantity of the exciting agent, or upon special predisposi- tion of the subject or upon the concurrence of several harmful influences {relative causes of disease). The occasion which brings a harmful influence in relation with the body or subjects the latter to such influence, is spoken of as the predisposing cause (causa proximo). The principal factor in producing a lesion is known as the special, immediate or essential cause of disease (causa essentialis) ; among these it should be understood that either external harmful agencies which have gained entrance into the body or which operate upon it from without, or some already existing tendency toward disease may be included. For example, pasturing upon some upland infested with anthrax affords the opportunity by which the anthrax bacillus as the essential cause of anthrax gains entrance to the body ; an injury, the favoring condition for wound infection by the essential cause of tetanus. Anything which promotes the action of an injurious agent may be regarded as a contributary cause (causa auxilians). Pathological influences may be divided into the following groups : 36 Causes of Disease. 1. Disturbances of Nutrition and Alimentation: Abnormal states of nutrition depending on irregularity in the water or nutri- tive elements afforded. 2. Obstructions to Respiration: Interferences with oxygen convection. 3. Functional Disturbances: Depending upon fatigue, upon overexercise of the organs. 4. Thermic Influences: High or low temperatures. 5. Electric Agencies. 6. Mechanical or Traumatic Agencies. 7. Chemical or Toxic Agents: Poisons. 8. Microbic or Infectious Agents: Micro-organisms belong- ing to the protopbytes and protozoa. 9. Animal Parasites: Of the class of worms and arthropoda. Disturbances of Alimentation and Nutrition. Total deprivation of food without water supply (complete in- anition) leads, in case of the higher vertebrates, to rapid loss of bodv-weight. emaciation and death in the course of from one to four weeks. A\'ith absolute rest (as in case of imprisonment in a caved-in mine) an adult man may retain life without food and drink for about twenty days : exertion hastens the end. Strong dogs have lived under similar conditions for thirty-six days ; horses and cats should live for about four weeks with absolute rest. Guinea-pigs and rats die within three to nine days. Liberge states that a well-conditioned cow. which had wandered into an out of the way place and had remained there forty days without food and without opportunity for much exercise, picked up quickly on a milk diet and was in tolerable condition eight days after being set free. If water is obtainable abstinence from food can be endured without permanent harm by man and carniverous animals for from two to four weeks, and the fatal end may be postponed for a considerably longer period. A cat experimented on by Bidder, weighing two and one-half kilograms, died on the eighteenth day from star\-ation after having lost 1,197 grams (water consumed, 131. 5 grams). Birds of prey (eagle) endure hunger and thirst for twenty to twenty-eight days; small birds only two to nine days, rvlascagni has recorded a turkey's having fasted for twenty- nine days. In case of cold-blooded animals the requirement for food is so small that water-salam.anders and turtles mav live for Disturbances of Nutrition. 37 a year, snakes for six months and frogs for nine months, taking nothing but water. When fasting an animal must furnish whatever energy is necessary for the maintenance of its proper temperature and for its organic functions (muscular activity and circulation) by the destruction of its body tissues, nourishment from external sources being impossible or insufficient. How the destruction of tissues, an actual self-combustion, takes place and how the vital organs live upon the less important structures, is well shown by the com- prehensive studies of E. Voit. Fat and glycogen are first sacri- ficed, and as long as these substances are present the albuminous elements are not subject to the destructive process, the muscular structures afterwards bearing the greatest part of the loss. Loss of weight and atrophy are most marked in the omentum and the fleshy parts (also the fat and glycogen stored in the liver), and fat animals succumb to starvation later than lean ones Accord- ing to Chossat, young, poorly nourished pigeons die after three days with a loss of one-third their body-weight ; plump ones after thirteen days, with a loss of half their weight. The heart shows the least loss in weight (its constant activity and functional stimu- lation hindering its atrophy) ; the central nervous system similarly loses but little, and the diminution in the red corpuscles is com- paratively unimportant. (Lipomata are unaffected in starvation; attempts to cause their removal by starvation have been un- successful. — Samuel.) Death from starvation takes place after the development of great muscular weakness, with complete loss of power and deep stupor (Samuel). In the bodies of animals dead from this cause are to be noted muscular and glandular atrophy, passive congestion and degenerative changes, together with scanty contents of the small intestine and diminished lumen of the latter. Complete inhibition of water (as in feeding with material arti- ficially deprived of its water) acts quite as effectively as hunger, death taking place in from eight to twelve days. Animals, un- able to quench their thirst, refuse food, and the organism is unable to adequately supply the fluid secretions necessary for digestion. Death probably is due to the retention in the system of injurious metabolic products (with poisonous qualities), which cannot be flushed out. Actual drinking of water may very well be avoided by a number of animals (rabbits, guinea-pigs, cats or parrots) without injury to health, provided the food ingested contain water. 38 Causes of Disease. Diminution in the amount of food ingested, undernutrition (relative or incomplete inanition), is often met with in connection with diseases of the alimentary tract; its consequences are pre- cisely similar to those of total withdrawal of food, save that the progression of the case is slow^er. Usually the condition is ac- companied by a diminution of erythrocytes in the blood (inanition ancemia), tlie alimentary disease producing wide disturbance through fluid-waste (diarrhoea) and other complications. Faulty composition of food causes partial starvation, the body suffering loss in its fat, albumen or carbohydrate should its nour- ishment lack or contain but an insufficient amount of one of these substances, or should the animal by preference and exclusively feed upon only one of these types of nutritive material. Impoverish- ment of the diet in such manner brings about emaciation and physical weakness. If lime should be deficient in the food and water supply the skeleton will fail of its most essential constituent, that which gives it its rigid strength, and the bones become soft. Respiratory Faults. All animals die by asphyxia* if their supply of oxygen be prevented. A wide range of factors may bring about a diminu- tion in the proportion of oxygen contained by the blood, asso- ciated as a rule with insufiicient separation of the carbonic acid and its consequent high proportion in the blood. Primarily this may result from the insufficient access of atmospheric air to the respiratory organs, as by closure of the superior orifices \ smoth- ering] or by obstruction of the respiratory tube [choking] and constriction of the latter {strangulation, compression of the larynx or trachea) by fluids and foreign bodies (the latter also by lodging in the pharynx and occluding the trachea), pres- sure upon the larynx and trachea by tumors, obstruction by tumors or swelling of the mucous membrane in the folds of the glottis or in the bronchial tubes, collections of blood, fluid or coagulated exudates in the lungs and bronchi, A second group of asphyxiating causes includes interference ♦The editor is here taking the liberty of using the word asphyxia as the general term, including smotherinfi as meaning respiratory obstructiun, operative at the respiratory orifices, mouth and nose- : clinking, respiratory obstruction operative within the mouth, nasopharynx or oesophagus (pressing on the larynx or trachea) ; strangulation, respiratory obstruction by constriction or pressure from without upon the larynx or throat generally ; suffocation, respiratory obstruction by any type of cause operative below the level of the larynx, either within (as a suf- focative gas) or without (as pressure upon the chest). In English this meaning is attached to asphyxia, although as Prof. Kitt indicates In the present section it really means pulseless; his own general terra is "Ersti-ckung." Respiratory Disturbances. 39 with the respiratory movements, as in case of rupture of the diaphragm, the principal muscle of respiration, in case of its' immobility or when it is forced forward by flatulence, in case of marked pressure from without upon the chest walls (animals standing pressed together in railway cars), or in case of pressure upon the lungs by large fluid collections in the chest cavities. Failure of respiratory movement may also occur from nervous origin (pressure upon the brain,, paralysis of the vagi, spasm of the bronchial muscles). Premature separation of the placenta or compression of the umbilical cord in the maternal canal prevents ox}gen convection to the foetus. Furthermore, passive congestion of the lungs, interference with the emptying of the pulmonary veins and haemic changes in which the blood corpuscles have lost their ability of taking up oxygen (carbon monoxide poisoning) render dift'usion of the gases so difficult that the same result of lowering oxygenation arises, and the respiratory disturbance eventually advances to the stage of sufifocation. The presence of irrespirable gas and the reduction of oxygen in the air of an inclosed space (instead of 20.8 per cent., perhaps only 2 to 3 per cent.) act in a similar manner. In one or other of such a variety of ways asphyxia may be the termination of a number of diseases and is the commonest cause of death. It is usually accompanied by the symptoms of dyspncea (17 Smirvoia, from wviw, difficult breathing, shortness of breathing), labored respiratory movements (sufi'ocative dyspnoea), marked increase in the cardiac movements, spasmodic twitching of the general musculature and loss of consciousness. Toward the close the respiratory movements become irregular, sometimes intermit and suddenly cease, the inspirations occasionally becoming very deep (terminal respiratory movement) ; and the spasms weaken the cardiac action (true asphyxia, actual pulselessness, from a privitive and 6 (7(pvy/j.6s, the pulse). When the diminution in oxygen is gradual in its onset these symptoms appear less promi- nently ; but as the tissues degenerate from the. insuflicient supply of oxygen (fatty degeneration of the heart, liver, kidneys) and as the respiratory nervous center loses its excitability, the patient dies from gradually increasing loss of consciousness and cardiac failure. According to the rapidity of onset of the fatal end and the causes of the asphyxia, the post-mortem findings present dif- ferent pictures. In addition to the local changes due to strangu- 40 Causes of Disease. lation, obstruction to the respiratory passages or the rest of the causes mentioned, the most common features of this mode of death are found in the tar-Hke, uncoagulated, dark condition of the blood (excessive presence of carbonic acid, deficient decarboni- zation) and in the presence of haemorrhages in the hmg and pleura. Excessive Functional Stimulation. All organic activity is accompanied by consumption of the essentially functionating material of the organs and by the formation of metabolic products. Both of these factors, especially the accumulation of the latter substances in the tissues of the organ, lead to a gradual reduction in efficiency, that is, to fatigue. This is normally corrected (restoration or reconstitntion of the part) during the intervals of rest, when the accession of arterial blood replaces what has been lost and the lymph current sweeps out the waste products (fatigue waste). Should the various or- gans be required to continue their activity without intervals of rest for a long time, or should they suddenly be overstrained, or called into functional effort beyond their physiological ability, their parenchimatous substance may be so affected by the height- ened metabolism and so marked an accumulation take place of the waste products of fatigue (carbon dioxide, phosphoric acid, either free or combined as acid phosphates), that exhaustion or wearing out results, with complete abolition of functional ability. This condition is clearly pathological if tissue changes can de- velop in the process and make the loss of function permanent (fatty degeneration or cellular atrophy), or if the cessation of function, momentary though it be. can cause in the vital organs disturbances involving the general economy or the actual death of the individual. Coincidence of other contributing causes (the weakened stage in fevers, traumatism or thrombosis) favors the development of such functional lesions from overexertion, as seen especially in the heart, the general muscles and in the nervous system. General muscular fatigue and cardiac exhaustion mav be the cause of death in overheated animals. Horses suffering from thrombosis of the abdominal aorta and its branches exhibit siens of functional disturbance of the muscles of the posterior limbs, even under moderate effort, because of their poor arterial supply and the accumulation of waste products from fatigue. The heart Functional Stimulation; Thermal Influences. 41 fatigued by prolonged effort may lose its power of contraction to such a degree that it becomes abnormally distended by the pres- sure of the contained blood (cardiac dilatation, insufficiency of the heart), with ensuing disturbance of the circulation. Over- stinuilation of the nervous system by sudden psychical shock is not only in man productive of serious results; fright palsy with cessation of cardiac action (paraplexis) has also been observed in the lower animals (fowls). A graduall}- and onl}- moderately increasing demand upon the muscles and glands acts as a stimulus to their functional activity, provided proper nutrition be afforded the tissue, and results in func- tional hypertrophy, that is, in an increased grozvth of the cellular elements corresponding to the demand' for zvork. This may be noted especially in tubular structures provided with muscular walls (smooth muscle), where there is gradually and spontane- ouslv developed an increasing competence for the w^ork required of the muscle, as in the thickening of the muscular layers of the bladder in case of gradually narrowing stricture of the urethra (v. functional hypertrophy). Thermic Influences. High temperature of the surrounding atmosphere (above the body temperature peculiar to the animal) may lead to failure of heat loss (heat stasis) and hyperthermia of the entire body with fatal termination by so-called heat-stroke. This is frequently ob- served in hogs when crowded in railway cars. The condition is most easily induced if the dissipation of the body heat by evapora- tion is diminished, and at the same time heat production in- creased in the animal by prolonged muscular eft'ort or by rich feeding. (It is known from experiments that warm-blooded ani- mals kept in well-ventilated warm chambers at 36 to 40° C. die, some in from one to three days, others in from ten to thirty days. The body temperature of such animals — rabbits — rises to 39 to 42° C. ; they become dyspnoeic and there is increase in the frequency of the -pulse; the haemoglobin of the blood is re- duced, and degenerative changes develop in the heart, the liver and kidneys. — Ziegler.) The cause of death is cardiac failure (heat rigidity) occasioned by the overheated blood, or may de- pend upon a thickening of the blood through excessive loss of fluid by sweating and respiration (fall of blood pressure, dimi- 42 Causes of Disease. nution in vascular tone). As anatomical changes are found red- dening of the skin (in hogs), failure of blood coagulation, dilata- tion of the right heart, venous hypersemia of the lungs, liver, kidneys and brain. The names insolation and sunstroke are ap- plied to that form of heat-stroke which is caused by the influence of the direct heat-rays of the sun upon the body, particularly upon the head ; it is thought to depend upon a paralytic dilatation of the vessels of the meninges and cortex of the brain, and the fiffection is accompanied by convulsions and marked symptoms of excitation (Birch-Hirschfeld). The influence of heat locally applied occasions, lesions known as hums (combustio), of various grades according to the degree of temperature, the duration of application and the resist- ive powers of the tissues to heat. Burning may result from con- tact with solid, liquid or gaseous heated matter, or from direct action of a flame or radiant heat. Short exposure to a tempera- ture of 40 to 50°, or longer exposure to 30 to 40° C. is pro- ductive of an inflammatory reaction marked merely by dila- tation of the capillaries (hyperemia) and redness of the part {inflammatory hum, erythema, hum of the first degree or of mild degree). The process is only superficial, leading at most to desquamation of the epithelium. Exposure to heat of 60 to 80° C. {hum of the second or intcmiediate degree) is productive, in addition to the hypersemia, of rapid exudation of serous fluid from tha dilated vessels beneath the epithelial layer. The cells of the stratum ]\Ialpighii are pressed apart by this, become swollen, are loosened from the papillary bodies, and the firm, horny portion of the epidermis is raised up to form a blister. Through minute fissures, easily made in this bleb, pyogenic bacteria may enter, the fluid contents through further exuda- tion [leucocytes] becoming turbid and purulent. Should the blister rupture the hypergemic papillje beneath are exposed, the repair of the epidermis starting from the epithelium at the mar- gins of the lesions or from remnants of the ]\'Ialpighian cells which were not destroyed. In case of mucous membranes, which are devoid of the horny epithelial layer, blister formation is not likely to take place, the epithelial layer desquamating in shreds ; and the denuded surface is covered by a coagulating exudate, the so-called croupous or false membrane. The more severe influ- ences of heat, above 80° C. {burns of the third degree), produce searing and charring {eschar formation) ; the burned Thcnnic [nflnciiccs. 43 tissue coagulates ; the blood within the capillaries is coagulated and stagnant, tlie tissue dying in consequence and being trans- formed into a brownish crust (or eschar). At the border of the actually involved and necrosed tissue inflammation ensues. Heal- ing follows by the separation of the charred material and the formation of scars, which are apt to be of a radiating, reticular appearance, and which by their contraction and shrinkage may cause considerable disfiguration. All these degrees of burning may coexist as the heat has happened to influence in a greater or less measure one or more places. In extensive burns of the skin (if as much as one-third of the body surface is involved) the subject is likely to die. even in case of burns of no more than the first or second degree. Death may take place within but a few hours after the occurrence of the accident with symptoms of impaired respiration, cardiac weakness and fall of the body temperature. In other cases the fatal end may take place after the course of a week, during which there may have been apparently favorable progress, pulmonary oedema and nephritis often developing in tlie meantime. Other cases pursue a course of some weeks' duration before the lethal end. The explanation of the dangerous features and fatal termi- nation of such burns is to be sought in part in functional dis- turbance of the skin in heat dissipation, fall of blood pressure, over- heating and inspissation of the blood (cardiac paralysis) and in part by the changes which the blood corpuscles undergo. Dif- ferent investigators (Salvioli, ]\Iaragliano, Castellino, Ponfick) have showm by experiment and observation upon human cases, that after burns of the skin the red blood corpuscles, partly de- generate (broken into small particles) and partly without any apparent structural changes, are incapable of conveying oxygen, and give up their hemoglobin (partly changed into methoemoglobin) into the serum, whence it is excreted by the liver and kidneys ; that, further, the formation of hyaline thrombi is apt to take place and that these alterations of the blood may be regarded as the cause of death. Low temperatures, which deprive the body of its proper warmth, may give rise to either local or general disturb- ances in warm-blooded animals. Sensitiveness to the power of withstanding cold varies very much in the different animal species. Fishes chilled to the freezing point may seem to be lifeless, their lymph frozen into solid ice ; yet they may com- 44 Causes of Disease. pletely recover from such a condition. Frogs are said to remain viable for hours subjected to a temperature of -2.5° C, with the heart frozen soHd (anabiosis). According to Koch, resuscitation is possible only by gradual thawing and providing only a part of the water present in the body has been actually frozen ; in case of rapid thawing, violent diffusion currents appear between the water emerging from its crystalline form and the concentrated albuminous solutions of the blood and tissues, which may destroy the tissues (Koch, Ziegler). Hibernating animals sleep but lightly with a blood temperature of 6° C, but soundly at 1.6° C. ; their cardiac beats sink to eight to ten each minute ; breathing is almost suspended, the movement of the lungs caused by the heart action alone carrying on the feeble gas diffusion in the lungs (Samuel). The hair and feathers (especially the winter pelt) of animals lessen the loss of heat by radiation and by convection of the [warm] air from the surface of the body ; in consequence of which animals are seen to endure with ease the ordinary cold, providing they are well nourished, move about freely and thus produce heat abundantly. [The loss of this protective element or the presence in the hair of much moisture favoring the ready convection of the heat from the body surface reduces tremen- dously the power of resistance to cold ; and one finds the cattle in the prairies freezing to death in a rain at a temperature con- siderably above ice-forming temperature, although were the hair dry and capable of holding the layer of warmed air close to the skin the animals would have shown no signs of discomfort.] If there be diminution of heat-production because of insufficient nutrition, and extreme cold, even well-pelted animals (hares and deer) and birds may be frozen to death. Death by freezing takes place by loss of sensibility of the nervous system, with fall of body temperature, diminution in the frequence of the cardiac and respiratory movement, cerebral anaemia, loss of muscular power and blood coagulation. The local action of cold, varying with duration of exposure and intensity, causes tissue changes of the same types as in burns (frosting, congelation). Primarily there results a constric- tion of the vessels of the part exposed (local anaemia), after which, if the cold continue, the nerves and muscle tissue of the vessel walls become paralyzed and dilatation of the vessels ensues with increased blood content, this condition usually returning to Thermic hiftnences. 45 normal when the low temperature of the part is corrected. Tem- peratures below the freezing- point are, however, likely to so disturb the vessel walls that inllammation of the tissue (swelling and redness of the skin, frostbite, chilblain) develops with or without the formation of blisters ; or after especially long and severe exposure the blood and lymph circulation cease and the tissue dies as a result. The necrotic area may be separated from the normal by inflammatory reaction, or if it remain moist may undergo putrefaction through the influence of invading bacteria. The extremities are the parts of the body most commonly sub- ject to freezing, but it is seen rather seldom among animals, for example, the scrotum in bulls (Baiit:^), the paws in dogs, in horses the thick skin of the hoof, particularly the crown and pastern. Jewsejenko and Cadiot have recorded instances of necrosis from freezing of the deeper part of the foot in horses (in the Russo-Turkish and Franco-German wars, as well as in Algeria). By the term catching cold (chilling) is meant the pathogenic action of heat loss not sufficient to cause freezing, but produc- tive of functional disturbances and inflammation of nerves, muscles, joints and internal organs. The laity commonly and primarily for almost all afifections attributes chilling as the cause ; and even the physician often evades the question as to the origin of some malady with the vague phrase of the possibility of catch- ing cold, because of the obscurity of the aetiology of the case. Many diseases formerly regarded as produced by exposure to cold are now recognized in the advanced state of ^etiological in- vestigation as infectious, although undoubtedly there is a group of afifections in which chilling of large areas of the skin and mucous membranes may with confidence be held responsible as the causal agency. Such a relation is evident in cases where, after unusual exposure to cold (thorough soaking, strong draughts, falling into icy water, heat loss by radiation to some neighboring cold object as a stone wall) there immediately develop in the chilled parts pains, functional disturbances and symptoms of in- flammation, or where in a short time these phenomena without other demonstrable cause appear in the subjacent or more distant parts of the body. Cats almost invariably become sick if they become soaked by falling into the water, wdiile flocks of sheep have been attacked by pleuro-pneumonia directly after wool washing if, while wet, they were left exposed to cold air. The 46 Causes of Disease. occurrence of paroxysms of colic (dysperistalsis) in sweating horses after cliilling of the surface cannot be denied. Rabbits and guinea pigs dipped into ice-cold water have been known to quickly sicken and die from pulmonary and renal inflammatory affections. As a further illustration it is well known that the peritoneum is very susceptible to the effects of lowered tempera- ture, and that in case of extrusion of the viscera or in operations involving the exposure of the peritoneal cavity there often arise, even at a temperature of 21° C, entirely from the chilling (under conditions of asepsis and in the absence of other causes), a gen- eral depression of temperature, attacks of colic, peritonitis and perhaps a fatal termination. Hofer has observed that chilling may affect even fishes, provided they be suddenly changed from a warm water to a cold ; and that such chilling causes changes in the skin (desquamation and necrosis of the epithelium). Attempts to frame a theory explanatory of the real nature of chilling have as yet been unproductive of any definite informa- tion on the subject. If it be assumed that the blood in the cutaneous vessels is chilled, it remains imexplained why practi- cally only isolated parts of the body are affected, although the chilled blood flows on to other organs. Excretion of blood pig- ment in the urine (hsemoglobinuria) after exposure to cold might well be explained upon the idea of chill effects upon the blood causing destruction of the corpuscles, yet in such cases of hsemoglobinuria there is usually a previously developed myositis and the red color of the urine is looked upon as a result of the liberation of muscle pigment and not as depending solely on blood destruction. The chilling of the skin causes extensive vas- cular constriction and the blood is forced from the surface and accumulates in the internal or more deeply lying parts of the body. Why in these cases the blood is not evenly distributed in the body, but collects in special localities, is an open question. Sudden exposure of a cutaneous or mucous surface to cold un- doubtedly causes an appreciable vascular tonic contraction, which may be ascribed to stimulation of the vaso-motor nerves. This vascular spasm is not limited to the area directly affected by the cold, but extends consensnally or reflex! y to adjacent or symmetri- cal, or distant vascular areas (Samuel). If, for example, one dip a hand into very cold water the other hand also becomes paler (Samuel), and probably everybody has had the experience that oc- Thermic Influences. 47 casionally a sudden chilling of the feet brings on directly a reflex sneezing and nasal catarrh. Rossbach has observed in experiments upon cats that by applying cold compresses over the abdomen vas- cular constriction passing over into vascular dilatation develops in the mucous membrane of the respiratory passages. There usu- ally succeeds upon the vascular constriction a relaxation of the vessel walls with which is associated a marked congestion (vid. Hyper?emia). Such disturbances are. of course, commonly cor- rected, the vascular constriction and internal congestion together with the vascular relaxation disappearing, and the chilling is realized but for a short time as a sense of cold or brief catarrhal affection by the subject. \\'hy the same adjustment does not occur in all cases is not clear. We only know as a fact that the chilling leaves in the skin itself practically no anatomical altera- tions, that the sensitiveness of the nerves, contractility of the vessel walls, the circulation and perspiration are entirely re- stored, while in the deeper structures the vascular spasm and the succeeding vascular dilatation are apt at times to be pro- longed. Sometimes, as further consequences, local engorge- ments, nutritive faults of the tissues, inflammatory exudates, ex- cessive mucous glandular secretion are to be seen ; sometimes catching cold may manifest itself only by nervous symptoms, functional disturbances and sensations of i>ain and may abso- lutely fail to give any idea concerning the anatomical changes of the tissues. Aft'ections which arise in consequence of catching cold are often but transient and are very apt to change their location in a system of tissues, appearing successively at different points along the larger nerves and in muscular regions and at dift'erent joints. For this reason they have been called rheumatic affections. [While it is true, as the author indicates, that the varied effects of chilling of the cutaneous surface are not susceptible of a simple explanation, there are certain probable influences which can scarcely be overlooked. The development of congest- ive states in some mucous membrane in connection with the more or less widespread vascular changes beginning in the skin may be held as oft'ering favorable conditions for the more active growth and penetration of some microorganisms, which perhaps in the normal condition, although present, were unable to advan- tageously invade the membrane, and many of the catarrhs which follow refrigeration undoubtedly show clear evidence of such in- 48 Causes of Disease. fectious agencies. The old idea that by causing a more or less prolonged contraction of the cutaneous vessels the skin secretions are reduced or prevented and that in this way there tend to accumulate metabolic or other toxines in the tissues cannot be set aside. Such substances have been thought to perhaps possess irritant qualities which disturb the sensory nerves and muscle fibres and other structures, the rheumatic pains and stiffness sup- posedly arising in consequence. At least some weight is to be given to the readiness of disappearance of such symptoms when by warmth and exercise the general circulation is stimulated and skin secretion heightened, these toxines then perhaps finding more ready excretion from the body than could be afforded by the other excretory paths.] Electrical Influences. Powerful electrical discharges upon the animal body induce paralysis of the nervous apparatus (especially of the respiratory centre), electrolytic destruction of the red blood cells, local burns of the skin and laceration of the tissues. Death usuallv follows ; but the paralysis and unconsciousness may, after shorter or longer duration, go on to recovery. The larger animals (cat- tle and horses in the stall or in the open) are especially liable to be struck by lightning (Frohner, Ziegenbein). Contact with live wires and completion of the circuit through the bodies of horses occasionally takes place when they step upon the contact points of an electric railway in the street pavements or on a broken overhead wire.'"' Horses have been killed by a current strength of 500 volts, 100 amperes (Puntigam, Mouquet, Blanch- ard) ; alternating currents of 160 volts are sufficient to kill dogs (Birch-Hirschfeld). According to Leblanc, horses are exceptionally susceptible to electricity. A horse was killed, for example, by a relatively light current which the owner passed through the bit in order to divert the attention of the animal while being shod. Anatomical changes may be entirely absent when death has been caused by electricity, or the hair may be found singed and the skin burned by the electric spark ; and at the points of en- trance and exit of the lightning or current, as well as in the internal organs, the tissues may be lacerated, with which lesions ♦Birds sit on telegraph wires witli Impunity because they are not in contact with the earth. Electrical and Mechanical Influences. 49 haemorrhages of course occur. Along the entire course of the current tree-Hke, branching Hues of singeing (hypersemia and hremorrhages), the so-called lightning pictures, may be seen in the skin and intestines. In addition the blood is dark and un- coagulated, the muscles dark brownish-red, the endocardium stained by the altered blood, and the heart muscle at times the seat of hcemorrhagic infarcts. Mechanical Influences. Pathological changes are very frequently produced by me- chanical force. These are either lesions of tissue cohesion, ruptures (breaks in continuity^ Icrsio continui) , or of compression, as the constriction of a hollow organ, condensation of tissues or displacement of organs. If this be caused by external forces or foreign bodies the process is spoken of as traumatism {trauma, rh rpavixa, lesiou, lat. IcTsio) . The active agent is either a dull (fall, blow, jolt, pressure, pull, friction) or a pointed or sharp (stab, incis- ing) solid body. In the same way internal mechanical disturbances may be caused by adhesions of the tissues, tumors and other pathological products producing constricting influences, or by excessive blood pressure, abnormal gas expansion or pressure by fluids; or may involve the functions of organs (displace- ment of actively motile stomach, intestine, uterus or muscle). If the force gives rise to loss of continuity amounting to visible separation of the tissue the lesion is spoken of as a zvound, hurt, tear (vidnus, trauma in restricted sense) ; if affect- ing dense structures (as bones, cartilage or teeth), as a break (fracture) ; if the tissue be destroyed by compression, as a crush, contusion or bruise. Displacements (dislocations) are met in joints, bones or muscles, as zvrenching or luxations; in the intes- tines as ruptures (hernia), or tzvists (volvulus). The term stenosis is employed in connection with constriction and oblitera- tion of hollow organs ; where the closure is caused by some fac- tor in the inside of the organ it is spoken of as an occlusion stenosis; where it is due to external pressure it is said to be a pressure stenosis. The results of mechanical injury are extremely numerous and vary with the size and character of the producing agent, as well as of the local lesion, and with the relative importance of wounded tissue to the general organism. A wound is often 50 Causes of Disease. complicated by other factors, as from the entrance of microbic or toxic agencies through the opening or breach made by the foreign body, with the result of further alteration of the tissues. The traumatic agent may be at the same time the conveyor of such substances, or may itself be a living parasite. Intense mechanical force may sometimes without any evident lesion, sometimes with manifest lesion, cause serioivs and perhaps fatal effects upon the nervous system. For example, this occurs in vio- lent concussion of the body {commotio from com-rnoveo) , espe- cially if the vertebral column be directly affected (concussion of brain and spinal cord — the former causing the loss of conscious- ness, the latter bilateral palsies of the extremities, the bladder and rectum). What the precise anatomical changes are which in such instances take place in the central nervous system has as yet not been determined, autopsy usually showing nothing that is characteristic. Possibly the alterations are molecular. Death sometimes takes place suddenly, too, from blows upon the abdominal wall and viscera. Such instances are characterized by sudden loss of strength, fall in body temperature, cardiac fail- ure and diminution of nervous excitability. This condition is known as shock, traumatic stupor, collapse, traumatic reflex par- alysis. It is thought that the paralysis and cardiac failure in such cases is due to vagus irritation. Chemical Agents; Poisons. Substances which harm the animal body by their chemical ac- tion are known as poisons; the actual process of introduction of the poison and its action, as poisoning or intoxication. Probablv nearly all chemical substances can, under proper conditions, act as poisons, or, in other words, have a deleterious influence upon the tissues ; the mode and power of combination of the chemical and the amount and degree of concentration in which it is present in the body being important items. For example, a substance as essential for the bod\^ as sodium chloride will in large doses cause vomiting and fatal poisoning in dogs. The most poisonous substances, as hydrocyanic acid or nicotine, have absolutely no eft'ect when given in the minute doses of the homeopaths. Changes in the relation of the atoms and solubility may transform a non-poisonous substance into a poisonous one and vice versa; of the two forms of phosphorus, only the white is Chemical Agents. 51 poisonous, the amorphous red form being harmless even in large quantities. A number of substances which are insoluble in water, and which have practically no effect when brought in contact with the skin or when introduced subcutaneously, are changed by the hydrochloric acid of the stomach so as to become serious poisons ; for example, carbonate of barium is changed in the stomach into the soluble chloride of barium. On the other hand, there are substances which are apparently energetic poisons when in- troduced into the blood, but which are inert in the stomach be- cause they are completely neutralized by the albuminates of the gastric juice (Samuel). Many poisons belong to the mi)ieral kingdom or are artifi- cially made from minerals, as arsenic, mercury, iodine, bromine, chlorine, lead, copper and others, and the various compounds of these substances (oxides, sulphides, chlorates, chlorides, etc.). The organic compounds, as alcohol, chloroform, hydrocyanic acid, cyanide of potassium, carbolic acid and picric acid, especially [include many poisons]. The vegetable kingdom (Samuel) affords many examples of poisons. There are whole families of plants w'hose genera and species possess some poisonous principle common to them all. In many plants certain parts may contain a poisonous substance, while the rest may be quite free from it and edible (as is well known in case of potato plants, solanum tuberosum, w'hose leaves, blossoms, seed and immature fruit contain the poisonous solanin, while the tubers are quite free from it). A number of plants are innocuous, slightly or seriously poisonous, depending upon ques- tions of climate, location, character of the soil and cultivation ; the almond tree, for example, bears either sweet or bitter al- monds, according to the location. The most pow-erful poisons contained in the higher plants are the vegetable alkaloids (mor- phine, atropine, colchicine, digitaline, etc.). In case of the lower plants also, especially the bacteria, there are products, some of which are marvelously toxic, fatal to large animals in the most minute and scarcely appreciable amounts ; these substances, analogous to the alkaloids and enzymes, or of albuminous nature, are embraced by the terms toxines, to.ralbuuiens, foxenaymes. (See also chapter on bacteria.) Among animals there are a number known to be able to elaborate poisonous secretions within special glands, especially the venomous snakes {viper a berus, the common adder of Ger- 52 Causes of Disease. many; vipera Redii and ammodytes in southern Europe, the dif- ferent species of crotalus (or rattlesnake) in America, possessing poison glands in connection with the teeth or jaws. Scorpions, the females and neuters among honey bees, wasps and bumble bees possess poison glands and a sting at the posterior end of the abdomen ; toads and salamanders, wart-like skin glands ; hairy caterpillars, many biting flies, gnats and gadflies, salivary glands. There are certain species of fish, like the barbel, whose sexual glands contain a poisonous fluid and whose tins are provided with a poisonous substance derived from the skin glands. It is not certain whether the occasional poisonous qualities of edible mussels, oysters and star fish depend on transient gland secre- tions (sexual seasons), upon the food of these animals, or whether they arise from bacterial changes of the animal after death. The changes caused by poisons are partly limited to certain localities, partly connected with general anatomical and physio- logical changes.* The poisons may be arranged for classification in four groups, according to their modes of action: (i) Corrosive, locally irri- tative poisons; (2) Parenchymatous poisons: (3) Hccmic poisons; (4) Nerve and Cardiac poisons. I\Iany do not confine their in- fluence to a simple type, but Excite lesions and symptoms of mul- tiple character simultaneously. The corrosive and locally irritative poisons {caustica, irritan- tia) vary in their results with the dosage and concentration of application and with the character of the tissue with which they come in contact, ranging from simple hyperemia and inflammation to coagulation, eschar-formation and solution of the tissues. Such lesions depend upon special properties of the substances, as abstraction of water from the tissues, precipitation or solution of the albumens, formation of precipitates in mucus forming tis- sues, solution and decomposition of urea, conversion of fats and carbohydrates into acids, as well as production of a variety of chemical changes in the salines of the body or other destruction of the structure of the living protoplasm. Among these caustics and irritants (to the skin or mucous membranes by direct contact) are included the corrosive acids (sulphuric, nitric, hydrochloric, oxalic, osmic, acetic, carbolic,! etc.). the caustic compounds of the alkalies and alkaline earths (potassium and sodium hydrox- •The following is taken from the works of Samuel, Zlegler and Blrch- Hlrschfeld. tCarbolic acid or phenol is really an alcohol. Chemical Agents. 53 ides, quicklime, barium chloride), the corrosive salts of the heavy metals (salts of antimony and mercury, zinc chloride, zinc sul- phate, chromate of potassium, etc.), the poison of the beetle Lytta vcsicatoria, cantharidin, snake venom, the poison of the sting glands of bees, wasps and hornets, the salivary secretion of gadflies, stinging flies and mosquitoes, and the so-called acria or acrid medi- caments derived from a number of plants (croton oil, mezereum, etc.). A number of poisons, volatile or gaseous in form, may also cause dermal or mucous membrane irritation, especially to the lining of the respiratory tract during inhalation (irrespirable gases). Should these irritant and corrosive substances be ab- sorbed and be conveyed by the lymph paths into the blood and internal organs, they may cause, in addition to their local effects, associated disturbances of the heart and nervous system, the liver and kidneys. Substances inducing degenerations of these paren- chymatous organs may be spoken of as parenchymatous poisons, their effects depending chiefly upon alterations of tissue meta- bolism, regressive nutritive changes and formation of precipitates in the tissues. Among this group phosphorus belongs, capable of causing extensive fatty degeneration of tissues, especially the liver. Corrosive sublimate, chromic acid, cantharidin, which pro- duce marked changes in the renal parenchyma, are also irritants. The production of argyria, the impregnation of the tissues with minute black particles of silver after long continued administration of nitrate of silver, may be thought of as a similar process ; and lead is an excellent example of parenchymatous poisons, producing, as it does, a wide range of disturbances, palsies, de- generations and both local and general pathological results. The so-called hccmic poisons act principally by depriving the red blood corpuscles of their power to act as conveyors of oxy- gen, by inducing their disintegration, liberating and breaking up haemoglobin or causing thrombosis. Some in addition may cause lesions at the point of introduction, and perhaps directly influence the nervous system. Some of them are gases entering the blood through inhalation, others are in solution and are derived per- haps from the intestine or from wounds. The best known blood poison is carbon monoxide, a constituent of illuminating gas, which enters into combination with haemoglobin to form carbon- oxyd-haemoglobin, and thus prevents absorption of oxygen by the blood and induces a tissue asphyxia. A characteristic feature of CO poisoning is the bright, cherry-red color of the blood. Sul- 54 Causes of Disease. phuretted hydrogen (in poisoning from the gas of manure pits) acts partly by paralyzing the nervous system, partly by forming sulphmethaemoglobin, giving a greenish (almost cadaveric) tint to the blood. Hydrocyanic acid and cyanide of potassium also cause a rapid paralysis of the central nervous system, in addition to interfering with oxygenation of the blood cells and tissues (cyan- methaemoglobin, bitter-almond odor in the organs). Potassium chlorate, nitrobenzole, potassium nitrate and amyl nitrite cause marked destruction of red corpuscles and transform haemoglobin into methsemoglobin, in which the oxygen is more firmly fixed than in the oxyhgemoglobin. The blood, and of the organs in such instances the kidneys especially, take on a striking brown color. Extensive hsemocytolysis, with liberation and solution of the haemoglobin in the blood plasma, giving a blood-red color to the urine (haemoglobinuria), are caused by various toxines of fungous and bacterial origin (ptallin, helvellic acid), arsenu- retted hydrogen, anilin, nitrous acid (fumes), carbolic acid and other poisons. Coagulation of the blood and its sequels are seen in poisoning with ricin (from the seeds of castor oil plant) and abrin (from the seeds of abnis precatorius). Infectious Agencies. By the term infection (inficere, to put into, to inoculate, to taint) is meant the entrance into the system of a disease-pro- ducing microorganism capable of self-multiplication, a pathogenic microbe. Nature is richly supplied with microorganisms ; which on the borders between the animal and vegetable kingdoms represent primitive forms of living matter, in their minuteness are visible only with the aid of the microscope and are recognizable as consisting of but single cells. According to their classification as plants or animals, they are spoken of as protophytes or pro- tozoa. There are forms which are only visible with a magnifica- tion of 2,000 diameters, and even then as barely perceptible points without definable cellular characters ; and there are reasons for believing that still smaller organisms exist, invisible with our present optical instruments, but by no means unreal, being dem- onstrated as corpuscular entities by other methods, as by their detention in filtration or by inoculation (so-called invisible microbes). Infectious Agents. 55 Even in ancient times the idea prevailed that devastating epidemic diseases \vere caused by a Hving contagion (co)itagium vk'uni sive aiiimafiiiii) . The nature of these conta^rions re- maincd hidden, Iiowever, to the physicians of antiquity ; and the impossibihty of determination led, especiahy in the middle ages, to the wildest conjectures as to the nature and origin of epidemics. They were attributed to evil spirits, deemed punish- ments from on High, fancied the results of supermundane pow- ers, of influences of the stars ; their origin was sought in con- ditions of the weather, in magnetic and meteorological processes, in putrid gases and in peculiarities of the soil ; and the hidden factor was characterized as a coiistititfio cpidcuiica or pcstilens. It is only about fifty years that our conceptions as to the real nature of epidemics began to become clearer and an assured foundation became established by precise observation — when, with the aid of the microscope, it became possible to demonstrate the existence of low vegetable organisms as foreign and invading elements in the diseased body and to determine the role which they play in the production of disease. In the last few decades this phase of science, stimulated and reorganized by the luminous work of Louis Pasteur and Robert Koch, improved by many technical aids and demonstrative methods, has fully disclosed the developmental history of many infectious diseases. Advances of tremendous significance for the whole of medical science, dis- coveries and experiences of the greatest consequence in the com- bating and cure of diseases, have been attained in this line of study. The demonstration of the relation which a given microbe bears to a given disease has been especially facilitated by the success of artificial cultivation of microorganisms outside the body (in vitro, upon nutritive media) and of production at will at any time thereafter of the infectious disease by inoculation. Such experiments have been made not only in animals, but also in human beings many times ; and anyone conversant with the subject can convince himself b}- combined cultural and inocula- tion experiments that certain microbes cause certain diseases. The objection that the microorganisms are not the cause but the accompaniment or product of the disease can easily be proved worthless. Of course there are microbes in the body which have nothing to do with disease, merely surface inhabitants of the integument and mucous membranes, able to penetrate into the 56 Causes of Disease. blood and internal organs only after death of the animal (mostly putrefactive organisms). Those parts of the human or animal body which are freely accessible are exposed to the entrance of bacteria as of anything else from the exterior. Many of these microorganisms find fa- vorable conditions for existence in the surface of the skin and mucous membranes, live and multiply there without doing harm, finding their nutrition in the secretions and refuse of such lo- calities. They come from the air where they exist in the dust, from food and drink, and, in fact, from any objects in which they exist and with which contact is had. In our alimentary tracts there are always millions of bacteria* and other fungi, in the stomachs of ruminants countless infusoria, all of which par- take of the nutrient fluid and aid by certain secretions of their own in the digestion of the food, but have no pathogenic action ; they are our table guests (commensualists) and stand in a re- lation of symbiosis to us (living together for mutual profit). As long as these conditions are maintained and as long as they obtain their nutrition merely from the dead material they may be considered as harmless saprophytes {(rairpbs, decayed; (pijrov, vegetable growth). Their harmlessness is explicable by the fact that these microorganisms are not in any way fitted for attack- ing the living substance of the animal body, and their metabolism gives rise to no products which might be toxic to the cells and tissues of the animal ; or whatever toxines there may be are quickly neutralized by the body secretions. Besides, their increase is held in check by the various adjustment powers of the body. The protective epithelium of the skin and mucous membranes prevents their penetration into the tissues ; they are expelled from the air passages by the activity of the cilia of the lining epithelium and from time to time by the expectoration of mucus ; many are retarded in their growth by the acidity of the gastric juice and by the intestinal secretions, as well as by the bile; large numbers are expelled with the excrement from the in- testines ; many dry up upon the surface of the body. Moreover, the various organs and cells, as the liver and phagoc3^tes and the blood particularly, contain substances of antitoxic and microbici- •A stained smear preparation should be made from the surface of the gums, tongue or throat of a convenient cadaver as proof of the interesting flora existing there and as evidence of the wandering corpuscles in our cellular constitution. Vld. for fuller consideration Kitt, Bakterienkunde f. Tierdrztc, IV. Aufl. Wien, 1903 Infectious Agents. 57 dal power ; and even thongh they have gained access into . the blood, bacteria may by these agencies be rendered harmless. There must, therefore, be special conditions afforded before a microorganism can become the actual cause of infection. In the first place the inicrobe must possess peculiar toxic pozvers. All microbes carry on metabolic processes and elaborate a va- riety of chemical substances in the medium in which they exist. If among these products there be any which are harmful to ani- mal tissue, the possibility of toxic action exists. Since Brieger called attention to these substances and indicated their relation to disease occurrence, many of these microbic poisons have been proved to exist by various investigators and the process of infec- tion is recognized as invariably connnected with intoxication. In one class of microorganisms, the bacteria, poisons have been demonstrated which are apparently free, soluble secretory products of the bacterial cells, and which exhibit strong simi- larity to ferments. These poisons are as yet not well defined from a chemical standpoint; they are quickly rendered inert by being heated (to 50° to 80° C.) and are peculiar in that they do not manifest their activity at once, but require a certain period of incubation. They are, moreover, especially peculiar in their specificity and in the fact that zvJieii introduced into a susceptible animal there is invariably a speciHc antitoxine gener- ated. They are, therefore, not a homogeneous product of all bacteria, but differ among themselves from their origin and the particular kind of microbe, each as a special product of a special process. These poisons are collectively called toxines. According to Ehrlich's theory, a toxine is a poison which possesses two specific groups of atoms, one of which, the Iiaptophorc, anchors the toxic molecule to the cellular protoplasm for which it has affinity ; the second, or toxophorc group, doing the harm, supplying the real poisonous agent. The toxines act then because they enter into chemical combination with the cells. (Vide Chapter on immunity, pp. 18 and 22.) The proof that a microorganism secretes a toxine and through it produces disease of the animal body is shown by the following : Many bacteria can be grown artificially upon nutritive culture media, as bouillon. If they secrete soluble toxines these will accumulate in the medium. If such a culture be passed through a filter impervious to bacteria, as a porcelain filter, the bacteria will be retained by the filter and the bouillon will pass through clear and quite free from bacteria. If there follow the injection 58 Causes of Disease. of such a germ-free filtrate (into a suitable animal) evidence of toxic action, especially a specific one, then we must be dealing with a dissolved toxine yielded by the bacteria. The best and simplest example of this is afforded by cultures of tetanus bacilli, the filtrate from which produces typical and characteristic te- tanus symptoms, the dry residue from the evaporation of the filtrate acting in the same manner. A second proof that the immediate agent of bacteria is their soluble toxine may be had by artificially removing the latter from the germs. If water be allowed to run for several hours through the residue of bacteria upon the filter they will be washed free of the toxines and can be inoculated in enormous amounts, by the millions, without giving rise to apparent harm (the inert bacterial cells being quickly destroyed by phagocytosis in the ani- mal body). Yet if these harmless bacteria be returned to a nutri- tive medium where they can again multiply, they produce poison anew, this collecting in the substance of the bacteria and in the fluid in such quantities that inoculation of even the smallest quantity, a very few of the bacteria, will produce fatal effects. The virulence of toxines is remarkable ; a hundred-thousandth of a cubic centimeter of the filtrate of a tetanus culture is suffi- cent to kill small animals, and a ten-thousandth of a milligram of the dried substance will do the same ; less than one milligram would cause tetanus convulsions in a human being. Such facts prove that some bacteria are provided with toxic agencies of frightfully dangerous power and explain why, when such causes of disease gain entrance into the human or animal body, they prove victorious in their conflict with the animal cells. Toxins do not act uniformly upon all animals. Intoxication oc- curs only when they enter into chemical combination, only in bodies whose cells possess substances (receptors) capable of union and having chemical affinity for the toxine. In bodies in which such receptors do not exist the toxine behaves as an indift'erent substance. This explains why certain animals show a natural immunity against certain toxines and why the bacteria producing tlie latter are harmless to these animals, as chickens are insus- ceptible to tetanus toxine. There are some germs which produce no toxine separable by filtration as a secretion, but whose toxicity is occasioned by sub- stances enclosed in the body of the microbe and fixed there ( endotoxines). Some of these substances are of albuminous na- Infectious Agents. 59 ture {toxalhnmoi, inycoprotciii, bacterial protein). They vary in their composition and modes of operation, some being peculiar to certain kinds of bacteria, others common to several forms. In general they act like albumens foreign to the animal, causing in- tlammatory changes, necrosis of cells and tissues and exciting fe- brile reactions. The dead bodies of the bacteria act in the same way to some degree, their toxic substances being freed only by the death and maceration of the microorganisms. A number of bacteria produce pathological changes also by elaboration of acids and gas-forming substances, as sulphuretted hydrogen. h\ addition to their chemical action it should be said that mechanical disturbances may be occasioned by bacteria which, in their multiplication, produce masses, perhaps for example ob- structing the blood vessels. The sum total of the pathogenic properties of a microbe is spoken of as its virulence. According to the quality of toxine produced and the energy of growth of the microbe in the animal body, there may be recognized gradations and differences of in- tensity of virulence of the various genera, species, strains and individual microbes'; their power of disease production corres- sponding with the same factors. Just as in artificial culture in a number of nutrient media a bacterium will either elabo- rate much toxine and grow rapidly or will produce but little toxine and grow slowly, according to the composition, reaction and temperature of the medium ; so in different kinds of animals there is a variation in capability of growth and toxine production of a given microbe. In adaptation to the conditions of nutrition afforded in a given body microorganisms may in greater or less measure lose the power of grovvth exhibited in some other body, may be altered in their pathogenic power ; this is spoken of as change of virulence by transmission. Such change may manifest itself either as an attenuation or as an intensification of virulence. The oldest known example of attenuation by transmission is seen in the change of virulence of the germ of smallpox ; variola, which in man is severe and marked by pock eruption all over the body, produces in the cow merely a local and mild eruption. In the cow, moreover, even in the first generation, it is permanently so attenuated that after reinoculation in man it gives rise to only a benign local eruption (not a general one). Wide differences of virulence exist between the different strains [growths of the 6o Causes of Disease. same organism from different sources] of the tubercle bacillus ; those obtained by culture from the human body have become almost non-virulent for cattle by their adaptation to man, although some strains are readily transmissible. Avian tubercle bacilli are innocuous for mammals (except rabbits) and conversely it is difficult to infect chickens with human tuberculosis. How- ever, Nocard succeeded, by placing human tubercle bacilli, inclosed in collodion sacks containing bouillon, in the peritoneal cavity of chickens, in so adapting their growth to the avian body that there- after (in later generations of the culture) they became pathogenic for birds as well as men. In part, at least, the variability in the virulence of microbes of the same species must be recognized as a reason for the occurrence of either a comparatively mild or a severe course of an infectious disease (formerly called genius epizooticus) as well as for its self-limited termination. For example, mouth and foot disease in some of the epidemics which sweeps the country runs an unusually severe course with high mortality, although under ordinary circumstances it is not a fatal disease, recovery taking place in the course of two weeks. The investigations of Loeffler have shown that the virus of this plague, if inoculated from cow to cow, gradually loses its pathogenic powers, whereas if alternately transmitted from cow to swine in a long series the virulence is maintained or even increased. It is interesting, too, that pathogenic organisms may be influenced in artificial cul- ture outside the body so that their virulence may be either in- creased or diminished {change of virulence by artificial culture methods). Toussaint and Pasteur, who were the first to estab- lish this possibility, have demonstrated that anthrax bacilli, promptly fatal to cattle, sheep, rabbits and mice, may be so attenuated in virulence by artificial culture in bouillon at a tem- perature of 42° C that they produce fatal effects only in mice. Similar facts have since been established in connection with a number of microorganisms capable of artificial cultivation, culmi- nating in efficient methods of prophylactic inoculation (Pasteur). This is easily understood when we realize that the attenuated germs give rise to but a mild attack of the infection when inocu- lated, which, however, leaves behind an immunity to the disease. On the other hand, an intensification of the virulence, even of microorganisms ordinarily without pathogenic influence, has been obtained by other cultural methods, as in nutrient media rich in Infectious Agents. 6i albumens and in the absence of oxygen (Wiener, Hueppe). From such considerations it may easily be appreciated that virulence is a very variable property.* It is also essential for the development of an infectious dis- ease that the infectious agent should be afforded a suitable path of entrance or atrium to the tissues. Mere contact with a micro- organism does not necessarily result in disease; there are often pathogenic microbes upon the surface of the skin and mucous membranes, the host in no wise suffering in consequence. The virulent germs of tetanus and of spreading gangrene are very fre- quently present in the intestinal canal of herbivora and omnivora, but without inducing pathological results as long as the mucous membrane is intact, their toxines being neutralized and destroyed by the digestive juices. So, too, pyogenic and putrefactive micro- organisms are found in large numbers in the intestinal contents and externally upon the skin in healthy human beings and animals, becoming ' pathogenic only in case of introduction into the lymph and blood through some tissue lesion. The ordinary places through which microorganisms gain ac- cess to the tissues are the external skin with its gland pores, the digestive and respiratory tracts, the conjunctival mucous sur- faces and the uro-genital passages. The protective epithelium of the skin and mucous membranes interferes with the penetration of most bacteria into the tissues and with their toxic action, partly because of the impenetrable barrier afforded (the horny epithelial layer), partly because the secretions of normal mucous membranes may wash off and destroy the microorganisms and dilute their toxines to such an extent that they are rendered inert or neutralized. This protective means is not an absolute one against some of the bacteria. Some may directly or by growth-extension penetrate the unaltered skin or mucous membranes; or, having gained entrance to sebaceous and sweat glands, especially the glandular ducts or lymph follicles (which are open upon the surface as in the pharynx and intestine), may be carried into the deeper structures by leucocytes (glandular or follicular infec- tion). Many microbes are provided with means of motility (flag- ella) and are thus able to penetrate into canals, or from a surface may find their way into slight depressions or inappreciable defects in the epithelium, where, after local increase, their toxic metabolic 'See further Kitt, Bakterienkunde fur Tierarzte, M. Perle, publisher, Wien, 1903, 4th edition. 62 Causes of Disease. products naturally come to reach such a degree of accumulation (concentration) that further tissue change is caused and opportu- nity thus afforded for further penetration by the germs. In this manner rats may be infected by plague by merely dropping upon the unaltered conjunctiva the plague bacteria; and the trypansome of dourine (horse) invades the body by its own motile power through the mucous membrane ; various bacteria, if they can gain entrance into a duct in the nipple of the mammary glands, may multiply luxuriantly in the milk and give origin to intense sup- purative inflammation. Microbes gain access to the digestive tract along with food and drink or may be swallowed after being inhaled with dust. The special point of infection (so-called intestinal or food in- fection) in this case is usually the lymph glands of the mouth and pharynx, or of the intestine ; by the same route it is possible that the toxic products of microorganisms, themselves confined to the interior of the intestinal canal, may be absorbed through the blood and lymph channels. Microbes gain access to the respiratory tract by inhalation (inhalation infection) with dried dust particles or in the fine dis- charge coughed up by diseased animals and subsequentlv dried. They are in this case in part retained on the nasal mucous mem- brane, in part adhere to the pharyngeal surfaces and may thence pass into the lymph follicles and extend by route of the lymph- atics or be swallowed (giving rise indirectly to an alimentary infection), or they may be carried by the currents of air into the lungs directly. Infection of the urogenital mucous membrane usually takes place by transmission of the germs from one to another indi- vidual in the course of sexual congress (coital infection). A most favorable opportunity for infection is afforded by wounds of the skin or mucous membrane (wound infection), affording access to the microbes into the lymph spaces and chan- nels of the connective tissue, to the subcutaneous and sub- mucous structures, favoring penetration into the peritoneal cavity and eventually into the blood. The wounds may be so small as to be inappreciable to the unaided eye, as some tiny abrasion of the epithelium ; or it may be that before the disease actually appears there may intervene a considerable period of time, the wound perhaps long healed, so that the point of entrance is en- tirely lost (cryptogenetic infection; kpvwthv, to conceal). This Infectious Agents. 63 latter is often the case when we are deaUng with a folHcular in- fection. The various pathogenic microbes do not possess uni- form powers of disease production, of multipHcation and dissemi- nation, granted that they gain entrance by one or other of the points suggested. Some give rise to infection, no matter from what point they are introduced ; that is, they are capable of activity from various atria (tubercle bacilli). Others require introduction in certain situations in order that they may show pathogenic efitects, a fixed point of access. For example, the te- tanus bacillus, as already indicated, can only be actively patho- genic from wounds ; the germs of vaginal catarrh and epidemic abortion naturally (partly effective also in case of intra- vascular inoculations) involve only the genital mucous mem- branes ; the bacteria of mastitis invade the lactiferous ducts onh' ; the bacteria of calf diarrhoea confine their activity to - the stomach and intestines. These peculiarities probably depend upon the presence at the appropriate points of entrance of es- * pecially favorable conditions for multiplication of the germs, other parts presenting certain interfering conditions. Many germs require some special underlying condition in order that they may live and nuiltiph'. For example, the piro- plasmata must get into the blood, because they can only obtain their sustenance under the conditions aft"orded by the living blood and die out in the body fluids. Other organisms, as the colon bacillus and vibrio of Metschnikoft', thrive best in the chyme and intestinal mucous membrane. Doubtless the condition of the cells and juices of the body plays some part in the question of development of the infection. The biological and biochemical differences in cells and fluids, designated as tissue predisposition and tissue immunity, are indi- cated by the fact that a given species of animal is by nature com- pletely resistant to a certain microbe and its toxine, surely lethal for some other species, and by the varying rates with which dif- ferent tissues are involved, as where practically only one of the tissues offers resistance to the growth of the microbes (as the resistance of muscles to tuberculosis) or where but a single tissue is involved. Hence the question of development of an infectious disease depends not only upon the existence of a given essentially virulent microbe, but also upon the defensive powers of the body, upon the antitoxic and microbicidal properties of its organs and 64 Causes of Disease. upon the mechanical obstruction to the penetration of the germ into the tissues (vide pp. 18, 21). The interval between the entrance of the microbes into the subject and the manifestation of appreciable symptoms is spoken of as the period of incubation. The length of this stage depends upon the vital peculiarities, the virulence and number of the microorganisms, and upon the site of the infection and the predisposing factors in the animal affected. If the microbes are capable of rapid multiplication and of generating large amounts of toxic material (as the bacteria of chicken-septicaemia, which rapidly increase in the circulating blood, or the colon bac- teria of mastitis which thrive luxuriantly in the milk of the udder) the period of incubation is usually of but a few hours' duration. Microorganisms of slow growth, as tubercle bacilli and actinomycetes, induce functional disturbances only after the structural changes which they bring about have attained a certain grade of development, and of necessity extend their period of incubation over weeks and months. Before the symptoms are appreciable clinicalh' extensive anatomical changes may in many cases have developed, whence it follows that a disease may be latent or occult in its period of incubation, although if the animal be slaughtered it is clearly seen to have been present for some time. For example, in the case of pleuro-pneumonia in cattle there are often found characteristic appearances of the pulmonary in- flammation in animals which have been slaughtered when appar- ently quite healthy ; and in hogs affected with erysipelatous valvu- lar endocarditis of intense grade, the disease may be discovered only on slaughtering, the animals having shown in life no symptoms of a character to have suggested the existence of their disease. In rabies and tetanus, in which the virus causes symptoms only after it has become fixed in the cerebral nervous system [the toxine in case of the latter rather than the germ itself], the disease manifests itself the more rapidly the closer the point of infection to the brain ; if the virus be inocu- lated directly into the brain the incubation lasts but a few days, while in case of ordinary subcutaneous inoculation it may be prolonged to weeks, the virus being at first retained in the lymph glands. Cases of infection of human beings by the bites of rabid dogs manifest rabies in 8-14 days where the wounds are in the face, but when the hands or feet have been bitten the period of incubation lasts usually one or two months, and sometimes the lnjcctiotis .liiciifs. 65 disease does not appear for a year. 'Jlie inllucnce exerted by the virulence, the amount of toxine and the ])artieuhir infec- tious germ u])(in the period of infection may he appreciated after introduction of tetanus toxine into mice: the symptoms of the disease, depending" upon the dosage, appearing after varying inter- vals from 12 hours to 2 — 6 days. The (lisscmiiiaUoii and nniltiplicafioii of pafluii^ciiic i^cniis in tJic body exhibit a number of peculiarities. .Some micro-organ- isms remain closelv confined to the immediate vicinity of the point of infection, giving rise from this localizetl situation tcj toxic results in proportion to their own disintegration and to the ab- straction by the fluids of the body of their toxic substances. Thus they may cause lesions only in the neighboring tissues or induce intense general disturbance after absorption. The tetanus bacillus, ft for example, does not grow free in the body (except in the uter- ine cavity, where, under anaerobic conditions, the organism can accumulate in large quantities after having once lieen introduced) ; in the course of a dav or two after inoculation it can no lonsrer be found at the site of infection (wound), nor elsewhere in the body. It disappears because of its disintegration and through the agency of the phagocytes. Its toxine, however, is absorbed and causes the ganglion cells to undergo necrobiotic changes. Often bacteria, as the pyogenic organisms, increase b\ multiplication at the site of infection, but are prevented from further extension by the defensive properties of the body. For the most part the germs are distributed from the point of infection along tlic lymph channels, in part at least because the newly developed germs are produced about the borders of the focus, are swept away in the lymph plasma or are taken up by the leuco- cytes and carried elsewhere. The local focus (local infcctio)i) en- larges directly into the surrounding regions (regional infection) ; and the microbes, conveyed by way of the lymph channels, are car- ried deep into the tissues to the lymph glands, from one site to an- other, from one lymph gland to another, until they finally reach the blood. They ma}- also gain direct entrance into the capillaries, veins and arteries from the point of infection (as in wounds or ulcers, or by direct extension by growth through the vessel walls) and be carried along with the blood current (embolic or hcemato- gcnous infection). There thus are produced at a distance from the point of entrance or primary focus of infection new deposits of the infectious agents : and either new local areas of disease,, 66 Causes of Disease. secondary metastatic foci of infection, are caused, or the micro- organisms are widely disseminated throughout the whole body {general infection, hactericcmia). As an illustration, streptococci of epidemic coryza in the horse gain access to the pharynx with the drinking water or with the inspired air ; they here first give rise to a purulent catarrhal inflammation, penetrate by direct growth into the pharyngeal follicles, gradually make their way along the Eustachian tubes to the middle ear and here set up a similar puru- lent inflammation. Being carried away by the lymph current and by leucocytes, they give rise to abscess formation in the retro- pharyngeal lymph glands, and by going lower, in the cervical nodes ; and, too, they may be swallowed and infect the mesenteric lymph glands as they pass along the chyliferous tract. Passing from, the lymph glands to finally reach the blood, they are disseminated by the latter generally throughout the body, and cause a variable num- ber of metastatic abscesses in such situations as the brain, lungs, liver and kidneys, eventually a septico-pysemia. In similar way infection of the umbilical vein in the new-born by pyogenic bacteria causes primarily a local abscess-formation at the umbilicus, fol- lowed by multiple venous-embolic abscesses in the liver, later in the lungs, the joints and elsewhere. It may happen that at the point of infection the local lesions are so slight as to be appreciable only by microscopic study, that the microbe passing from this point first lodges in the lymph glands or may perhaps even pass through several lymph-nodes without occasioning any disturbances, multiplying and manifesting its influences only after- it has gained access to the blood and circulated in the body and become fixed in this or that position at a distance from the original site of entrance. The tubercle bacillus, for example, may be absorbed from the intestines with- out causing any alterations in them, but giving rise to caseation of the mesenteric lymph-nodes ; or these may be traversed by it, the germ gaining access to the blood, and perhaps first deposited in the bone-marrow, where it gives origin to the primary tubercu- lous focus. The physiological movements and changes of position of the intestines and muscles aid in great measure the spread and dis- tribution of the invading and multiplying microorganisms : pyogenic microbes which have gained access to the peritoneal cavity are apt to be spread over the whole peritoneal sur- face by the peristaltic movement of the intestine, the resulting peri- Infectious Agents. 6y tonitis as a consequence being- generally a dilluse one. Tuber- cle bacilli having effected an entrance into the pleural or peri- cardial cavities multiply in the lymph and are actually rubbed into the whole serous surface by the movements of the heart and lungs. For this reason there usually occurs in these regions a disseminated, dense eruption of tubercles involving the whole pleura, pericardium and epicardium. So, too, currents in the secretory fluids on mucous surfaces are favorable to the dissemina- tion of microorganisms ; and the covering of these surfaces permits migration and generalization, especially of the motile forms. Tubercle bacilli may thus reach the larynx in the bronchial secre- tions from cavities in the lungs, and if retained may occasion laryngeal ulceration ; pyogenic bacteria from the pharynx may pass to the Eustachian tubes and middle ear in horses ; and in case of infection of the milk ducts of the nipple the dift'erent kinds of bac- teria in the milk and milk passages advance into the parenchyma of the udder and give rise to mastitis. The pathogenic action of bacteria is, as already indicated, for the most part a toxic process, but also in some degree a mechan- ical one; it is governed both by the properties and the quantity of the e.vfrcniely varied metabolic products elaborated by the individual microbes, but is also dependent upon factors deter- mined by the place of infection and by the predisposition of the tissues. Local and general eft'ects are distinguishable ; first by the fact that at the original point of infection and at metastatic locali- ties anatomical lesions are originated (inflammations, degenera- tions, necroses, proliferations, depending upon the nature of the microbe, both in the sense of a mere foreign body and of the pecu- liarity of its constituent materials) ; and, second, by the develop- ment of general metabolic disturbances, especially fever, from the generalization of the infectious agents and their products. In each case the phenomena are expressions of tissue reaction to the noxious foreign microbe undergoing multiplication from time to time in the system (v. chapters on fever, limiting inflammation). Each kind of pathogenic microorganism manifests a fixed mode of action, determined by its manner of multiplication in the tis- sues and the particular nature of its toxic product (specific action), and therefore produces a specific disease. In case of other causes of disease there is no uniformity of action, but, on the contrary, a variability ; or, better, it may be said that other or non-infectious diseases mav occur in the same form from the 68 Causes of Disease. effect of a variet\ of agencies. A nasal catarrh may be caused by the inhalation of (hist, irritant gases, chemical llnids, the influence of cold upon the external surface of the body, or from infection: cold may produce in one subject painful peristalsis (colic), in another muscular rheumatism, in a third a coryza, a pneumonia, an intestinal catarrh. In infectious diseases the body generally reacts with uniformity in a definite manner ; the basic symptoms and lesions are invariably manifest, and it is possible to decide from the presence of certain signs of the disease that a definite type of infection exists. By specificity, therefore, we understand that each infectious disease is the result of fixed in- fectious agents and not of anything else. Anthrax is always caused by the anthrax bacillus, and never by any other microbe or noxious agency of any sort ; glanders is caused by the glanders bacillus ; smallpox by the smallpox contagium. There are, how^- ever, some micro-organisms which, because of similarity of toxic properties and analogous modes of multiplication, give rise to the same anatomical tissue changes, so that clinically the same anatomical types of disease are produced by several kinds of germs (the groups of the pyogenic bacteria, the micro-organisms of septicaemia, of moist gangrene and of mastitis). Such in- fectious diseases are said to be polybacterial. Variations in flic duration of infectious discuses, modifications and degrees of anatomical changes, ore proportioned in the sei'cr- ity of the infection to the grade of virulence of the microbes, and are dependent as well upon the place of entrance of the infec- tion and the predisposition of the tissues. Just as a corrosive substance, an acid, depending upon whether it comes in contact with animal tissue in concentrated or dilute form, produces either an eschar, tissue necrosis, inflammation or mere hyperaemia. so a difference is appreciable in the action of microbes according as they are highly toxic or more or less attenuated. The importance of the factor exerted by the place of entrance of the infection is indicated by the studies of Arloing, Cornevin and Thomas upon the bacillus of symptomatic anthrax ("black leg") ; this micro- organism, if inoculated into the muscles and subcutaneously. kills animals after intense symptoms ; but if the inoculation be made into the trachea or intravenously there follows merely an abortive course, which, however, is succeeded by an immunity. \'ariations of susceptibility and resistive powers in different animal species and individuals to precisely the same infectious agent may cause Jiifcctioiis .li^ciits. 69 marked variations in the clinical and anatomical picture of the same infectious disease. I'hus a certain strain of glanders bacilli has been known to cause in a horse a chronic glanders lasting over several years, but in guinea-pigs and field mice a very acute type of the disease; the bacillus of hog-erysipelas, pro- ducing in one hog an acute septicaemia, to cause in a second a slight urticaria, in a third a chronic cardiac valvular affection. The influence of tissue resistance upon the disease picture is especially apparent when inoculations of the organisms of chicken- cholera of high grade of virulence are made into rabbits previously treated by serum injection. Rabbits which have not been previ- ously subjected to serum injection succumb to hypodermic inocu- lation of but a small number of bacteria as early as from 12 to 24 hours, dying of severe acute septicaemia ; those previously injected and then subjected to the same inoculation die only after 5 to 14 days, and then show extensive purulent phlegmons, purulent and fibrinous pleurisy and pericarditis, or merely an ansemia as a re- sult of the prolonged infection. Recovery from an infectious disease usually leaves thereafter a certain degree of ininiunity (v. active immunity, p. 2/). Sometimes several kinds of pathogenic organisms gain en- trance at the same time through one point of infection, the result- ant infection being thus a complicated one (mixed infection) ; or after the individual is attacked by one infection other types may invade (secondary mixed infection). The former condition is seen when the infective matter from the beginning contained sev- eral varieties of pathogenic germs, as where a wound is contami- nated with earth containing both spores of tetanus bacilli and pus bacteria, or where a cow's nipple is soiled with filth and dung m which there are streptococci and colon bacilli. So, too, micro- organisms which have existed indefinitely upon the surface of some mucous membrane may, if occasion presents, penetrate into the tissues along with some other type of infection and combine with the latter in producing pathogenic effects ; thus, should there be pro- duced by some foreign body an injury to the tongue or pharynx of the cow, the various putrefactive organisms living as sapro- phytes in the mouth may occasion with pyogenic bacteria a mixed infection. The second form of mixed infection, the successive invasion of a second or third pathogenic germ, may be noted where local changes 'from a primary infection bring about condi- tions which facilitate the access and growth of other microbes; as 70 Causes of Disease. when ulceration has occurred in the primary infection and the protective epitheHum has been lost, or when in the course of a disease the bactericidal substances normally present in the fluids of the body have been exhausted and the resistance of the tissues reduced in consequence. Not infrequently such mixed infection is to be seen in hog-cholera, the micro-organisms of which cause necrotic and coagulative destructive changes in the intestinal mucous membrane and general wasting; there is thus prepared so suitable a culture medium for the sputum bacteria and necrosing bacilli present in the pharyngeal mucus and in the intestinal con- tents that these readily penetrate into the tissues and materially contribute to intensify the disease and hasten a fatal termination. Admixture with or contamination (association) of an infection by one or more other types of pathogenic microbes, each with its special properties, and the combined action of all, as a rule causes a severe course of the infectious disease and occasions unusual pathological processes {compUcations). The mere presence and microscopic recognition of several types of microbes in any focus of disease or in the tissues of the cadaver by no means warrant, without other knowledge, the assumption that there has existed a mixed infection ; after the death of the animal great numbers of saprophytic organisms living on the surface of the mucous membranes wander into the organs, and necrotic or ulcerating foci in the lungs, intestine or skin are apt to harbor the same sort of organisms from the air or food (so-called symbiotic bacteria). The association of such essentially non- pathogenic germs, or, too, of pathogenic microbes with another pathogenic variety, may (as especially pointed by Leclainche-Vallee in studies on symptomatic anthrax) determine actual infection ; for example, a symbiotic bacterium may prevent phagocytosis by a negative chemotactic power and thus produce conditions favoring the increase of the other infecting agent. This should not be interpreted as meaning that a given microorganism cannot alone cause its special disease, and that only when in association with other microbes can produce its effect ; it merely applies to special conditions in which the specific infectious agent is attenuated or is situated in an unsuitable point for infection. All known pathogenic microorganisms are individually capable of giving origin to their peculiar infections, and each is the specific bearer of such infection. Those micro-organisms regarded as pathogenic may be classed in two groups : In the first group are microbes usually living in the external world, but inducing disease in the animal body if by accident they gain access to it (ectoge)ious infectious agents, facultative parasitic microbes). The diseases arising from this group affect individual animals here and there, or may attack a Infectious Agents. 71 number, provided there be opportunity of convection from their habitat in the soil to the animal body with water, food, etc. They are essentially of telluric origin, and it is customary to speak of spontaneous disease or miasmatic {t6 /jLiaafia, from fxiaivu, to con- taminate) origin in this connection. In the second group are included microorganisms which, being exclusively adapted to the animal body from an indefinite period, live and thrive in it as their habitat (entogeuous infectious agents, obligate parasitic microbes). Diseases occasioned by these do not appear as spon- taneous infections, but occur only when a human being or animal comes in contact with a previously infected individual or with desquamated or excretory material from such an individual in such manner that the infectious agent can pass to the former. Such instances are spoken of as contagious i)i feet ions diseases. [Among many there is to-day a strong tendency to deny the existence of pure miasmatic infections, and thus to regard the terms contagious and infectious as synonymous, such persons hold- ing that the so-called miasmatic diseases are caused by organisms which are essentially facultative parasites, und in more or less direct manner have come from previously diseased individuals. The difiference of view is by no means a vital one, and the author's recognition of their immediate derivation from a source other than a previously diseased individual is correct. In the sense that these facultative parasitic microbes once afifecting an individual may be further transmitted, his division, however, be- comes unnecessary, since in this manner all infectious diseases are contagious.] A certain number of infectious maladies may be acquired in both ways ; originating primarily from the soil, the microorgan- isms multiply in the animal body and then are transmitted from the diseased to other individuals (contagio-miasmatic diseases). The fact that some microorganisms thrive only in the animal body and die when in the external world is a phenomenon of adaptation. It may be assumed that all these obligate parasitic germs originally lived a free saprophytic life in nature, but having accidentally gained access to an animal body thrived therein and by rapid succession of generations usual to such low organisms acquired a special adaptation for the conditions thus afforded and lost their faculty of propagation outside. Changes in nutritional conditions are likely to cause changes in their metabolism, and the influence which invading microbes have 72 Causes of Disease. upon the tissues of the body depends in part upon their metaboUc activity and metabohc products. From investigations of Wiener it has been shown conclusively that a type of bacteria common to the human intestine and regarded as entirely harmless in this situation and in the excreta, can by special nutritive influence be so transformed as to acquire highly toxic properties (the so-called eolon bacilli, living as saprophytes in the colon). If fed ordina- rily to rats they give rise as a rule to no disturbances whatever, but if the colon bacilli have been cultivated for a few days under anaerobic conditions on a medium specially rich in albumen (eggs) they acquire an intense virulence, and if fed to rats produce a severe ami almost invariably fatal enteritis. Although such transformation of a non-toxic saprophyte into a toxic pathogen cannot ofif-hand be accomplished with other micro-organisms, this isolated fact proves that it is possible for infections of a character new and imknown to us to arise from time to time ; and as a matter of fact spontaneous infectious diseases do now and again appear which have not been previoi:sly observed and which are to be regarded as rarities. It is a pure accident when the special germs are brought into contact with the human and animal body ; and it is further conditional upon special circumstances of nutri- tion whether the microbe possess virulent properties, as in case of the meat intoxications caused by various microorganisms, sausage poisoning, diarrhoea and vomiting and wound infections. Some infectious diseases are of very frequent occurrence because the agent is widel}- disseminated in nature or because opportunities for transmission to the animal body are often afforded. For in- stance, the tetanus bacillus exists in the soil in many localities, and wounds are often contaminated by dirt, the opportunitv for tetanus infection being correspondingly common. Such wide- spread microorganisms and their infectious diseases are spoken of as ubiquitous. As the alpine rose and reindeer moss, palms and cacti flourish only within certain geographical limits, and as poisonous snakes and the different kinds of insects have their habitats only in certain parts of the earth ; so certain microbes occur only in certain lands, where alone, too, the corresponding infectious diseases arise as spontaneous affections. Such districts are foci in which annually a certain number of cases are likely to occur, and it is said that the disease is established in such places {indigenous, cudeuiic). Truly contagious diseases ma}- also be endemic, provided in a certain district (irrespective of soil Infections Agents. 73 conditions) there are al\va\s a number of animals suffering from the special infectious disease, so that others from these may in turn acquire the affection. When an infectious disease occurs in isolated cases here and there it is spoken of as a sporadic disease ; if many or great numbers of individuals are affected, it is spoken of as a plague, an epizootic {epidemic) ; if it extend over large areas, 'and if not merely one species, but many, are aft'ected, it is called a panzootic {pandemic). Animal diseases transmissible to man may be spoken of as androzoonoses. The separation of spontaneous from contagious infections, the recognition whether a microbe is miasmatic or purely contagious, is of importance in dealing with epidemic diseases ; the purely contagious diseases can be eradicated by measures protecting the well from the diseased animals and their excrementitious matters. This has been demonstrated in the extirpation of cattle plague, pleuro-pneumonia and hydrophobia from districts in which for- merly they were rife. SU^niARY OF THE AIOST IMPORTANT INFECTIOUS DISEASES AND THEIR AGENTS.* I. Bacteriaemias, Septicaemias. Bacillus az'iscpticus [Boct. az'iscpticuin s. az'icidufu ) , septic:emia of birds and rabbits (chicken cholera). Bac. pleuriscpticus, sporadic and epidemic septicaemia of all domestic animals (bac. hoznscpticus, suiscpticus) , deer and cattle plagues, pastcurcUosis hovis. Bac. antJiracis, anthrax of domestic animals and man. Bac. a\icn:atis nialigi:i, spreading gangrene of domestic ani- mals and man. Bac. sarcoplixscuiafos boz'is. symptomatic anthrax of cattle. Bac. gastroinycosis czis, bradsot of sheep. [Bradsot is a dis- ease of sheep in northern Europe, by man\' regarded as a form of symptomatic anthrax.] Bac. pcstis iarandi, reindeer plague. Bac. rhusiopathicc suis, swine erysipelas. Bac. suipesfifer, hog cholera. Bac. pcstis buboniccr, human bubonic ])lague, transmissible to swine and rats. *For detailed description and technique of investigations, v. Kitt, Bakterien- kunde f. Ticrdrxtc, IV. Aufl., Wien, lOUo. 74 Causes of Disease. II. Toxic Infections. Bacillus t eta III, tetanus in all animals and man. Bac. hotulinus, sausage poisoning in man. Bac. enteritidis, meat poisoning in man. Bae. dysenteries zitulorum, diarrhoea in calves. Vibrio Metschnikovi, vibrio cholera of chickens [microspira Metschnikovi, irregular] . III. Inflammatory and Pyogenic Organisms. Staphylococcus pyogenes aureus (albus, f!a-rus, citreus), sup- puration of wounds, furunculosis. Streptococcus phlogogenes sive pyogenes (various forms), suppuration of wounds. Micrococcus tetragenns, umbilical suppuration in calves. Bacillus mallei, glanders in horses and man. Bac. lymphangitidis ulcerosa;, lymphangitis in horses. Saccharomyccs farciminosus. furunculosis in horses. Strcptothrix farcini boiis, furunculosis in cattle [Nocard's pseudotuberculous nodules in the skin and viscera of cattle]. Streptococcus equi, contagious coryza of the horse. Bacillus acncos cqiii, contagious pustular dermatitis of horse. Bacterium phlegniasice ubcris (a number of varieties), mastitis in the cow. Streptococcus mastitidis (a number of varieties), mastitis in cow. Micrococcus mastitidis gangramoscc oris, mastitis of sheep. Bacillus py clone phritidis boris, nephritis of cow. Bac. pyocyaneus, purulent inflammations. Bac. coli connniiiiis (a number of varieties), various forms of cellulitis, mastitis, nephritis and enteritis. Botryomyccs ascofornians, suppuration and granuloma forma- tion in horse. Cladothrix canis, various suppurations in the dog. IV. Diphtheritic Necroses. Bacillus nccropJiorus, traumatic necrosis, multiple coagulation necrosis of mucous membranes, liver and lungs in cow, horse and sheep. Bac. diphthericc colunibarum, pigeon diphtheria. Infectious Agents. 75 Bac. diphtheria avium, chicken diphtheria. Bac. diphthcricc Jioiniiiis, (hplitheria in man, exceptionally in cats and birds. V. Tuberculosis and Actinomycosis. Bacillus tuberculosis, tuberculosis of man and the lower ani- mals (varieties in birds and cold-blooded animals). Bac. bronchiolitidis vituli, cheesy pseudotuberculosis of the lungs in the cow. Bac. pseudotuberculosis oz'is, in sheep. Actinomyces bozis, actinomycosis of cow (with varieties). Streptothrix caprce, pseudotuberculosis of the goat. VI. Specific Diseases of the Sexual Organs. Bacillus abort ivus z'accaruui, epidemic abortion of cows. Micrococcus abortivus equi, epidemic abortion of mares. Streptococcus zaginalis vaccariim, contagious vaginitis of cows. (Trypanosoma eqniperduni s. tJagelose), dourine in horse. [SpirochcFta pallida, syphilis in man?] VII. Pleuropneumonia. The infectious agent of contagious pleuropneumonia of the cow. VIII. Epidemic Diseases Caused by TJltramicroscopic Agents. Contagium of foot and mouth disease, in cattle, swine, sheep, and transmissible to man. Contagium of cattle plague. Contagium of smallpox in man, transmissible to cow, horse, rabbits. Contagium of sheep pox. Contagium of rabies of dog, transmissible to man and all mammals. Contagium of Lombardy chicken plague. IX. Diseases Due to Flagellata. Piroplasmata and Sporozoa. Trypanosoma Evansi, surra in domestic animals in India. " Brucei, nagana in African animals. " eqniperduni, dourine in horse. 76 Causes of Disease. Trypanosoma Theileri, African cattle plague. [ " Gamhiense, African sleeping sickness in man.] Plasmodium malaria equorum, African equine malaria. [Plasmodium of human malaria — tertian, quartan and a^stivo- autumnal types.] Piroplasma bigcminum, epidemic haemoglobinuria of cattle, deer and sheep. Piroplasma caninum, infectious jaundice of dog. Sarcosporidia major and minor, parasites of muscle and cel- lular tissue in swine, cattle, sheep, goats and horses. Coceidium oviform e. dysentery of cow, intestinal and biliary duct parasite of rabbit (also in man and dog). Diseases Due to Mould Fungi. Moiiilia eaitdida, thrush in man and birds. Trichophyton to)isura}is (numerous varieties), bald patches in cow, man and dog. Achorion Selionlcinii (numerous varieties), favus in man and lower animals. Dermatomyces gallinarum, scab of cock's comb. Aspergillus fumigatus, pulmonary mycosis in birds (excep- tionally in horse and cow). Animal Parasites. Food and conditions favorable to the existence of a variety of animals and plants are afforded by the human and animal bodies, both in the fluids and tissues, and, too, in the nutrient ingesta and in the excretory and waste matter. When some organ- ism both acquires its nutrition and resides upon or in the body of another individual the condition is spoken of as parasitism (Trapa along with ; <^^-ros. food). A parasite, therefore, is a form of life zi'hieh either transiently or pernianentl\' lives upon or in the body of another organism for the purpose of obtaining its nutritio)i tJierefrom (Braun. Heller). According to their origin from one or other of the two kingdoms in nature, they are separable into vegetable and animal parasites ; those which hve on the surface of the body are spoken of as ectoparasites or external parasites (epiphytes, epizoa), those whose habitats are within the body as internal parasites or entoparasites (entophytes, entozoa). In the preceding chapters the discussion concerned infestment Animal Piirasilcs. yy by microorganisnis ai^prcciablc only with the aid of the niiero- scopc. the protophytcs and protozoa, a condition spoken of as in- fection wlien leading" to disease. Some of these micfobes well merit the name parasites, since the animal body in which they exist is the source of their nutrition, but the toxic properties of the most of them are so conspicuous that we are likely to think of these not so much as ])arasites, but as comparable to poison- ous plants. A mmiber of forms of worms and arthropoda (zooparasites) have gradually assumed the character of true parasites and actu- ally live and subsist upon the body structures. ( )ccupation of the body, either externally or internally, spoken of as i)n'asioii (iiiz'adcrc, to penetrate), is apt to give rise to a varied group of tissue alterations and disease processes (invasion diseases [iiifest- ment] ). The individual in which such a zooparasite finds shelter is to be looked upon as the host of the parasite. Some infest the host only for a brief period as necessary for the acquirement of nutri- tion (transiriif <^r tcutporary parasites) , or for the time essential for the completion of one or more stages of their development, among which groups respectively fleas and the larvfe of gadflies are examples. Others are persistent and pass their entire existence as parasites (habitual or pcniiaiicut parasites). The life of this latter type ma\- be passed in some instances entirely in one host (inono.rcnoiis parasites: ^bvos, one; ^evos, host), or may be dis- tributed over several hosts (hetero.veiioiis parasites). Invasion of a host at times is merely the result of accident, in which case the parasite is usually taken in with food: in other instances this or that parasite may by its own independent move- ments gain entrance into the body. Parasitism may he referred to two underlying conditions, adaptability of the parasitic organism to the conditions of life af- forded by the body of the host and the biological variability of the former. Worms and arthropods which have assumed parasitic char- acteristics undoubtedly at one time lived independently in nature. It may be imagined that one of these low types of animals by acci- dent entered the bodv of some higher animal, and, finding condi- tions favorable for the acqiiiremcnt of food, remained and multi- plied ; that the offspring, now native to the body of the host, did not again seek a free state, but continued as parasites, being from birth accustomed to the altered environments. Such sup- position is justified by the fact that some parasites still show rudi- 78 Causes of Disease. ments of organs worthless to them in their present form of life, but which were evidently inherited from their free-living ancestors. For example, in lingiiatnla tccnioidcs, a permanent parasite of the nasal fossae of the dog, there are rudimentary feet, probably better dev^eloped in the free-living predecessors, but stunted in these parasitic descendants from lack of use. In the same way may be explained the absence of wings in parasitic insects ; for example, sheep lice have probabl\" developed through atrophy of their wings from disuse of these organs, for there are allied species of insects which are not parasitic and possess wings. On the other hand, gradual adaptation to life upon an animal host leads to the acquirement of new peculiarities, on the part of the parasite, as a transformation of masticating mouth parts into piercing and suctorial organs and the development of special types of organs for attachment and holding. Such adaptations and transforma- tions of structure are of such common occurrence throughout na- ture, even in case of the human body (formation of a horny sole on the back of the foot, originally soft, in cases where from some disease the dorsum of the foot is turned down and walked on ; transformation of the toes into prehensile organs by practice), that, as it is true in the higher animals, there is no wonder that it should occur in these lower invertebrates whose tissues are much more capable of such adaptive growth. The newly ac- quired characteristics become fixed in the succeeding generations because of heredity and because of uniformity in the vital condi- tions about them ; some species which have gradually assumed parasitic nature are finally restricted entirely to a parasitic life and are unable to live in the external world ; others pass only a part of their lives, a definite developmental stage, as parasites, and for the rest of their time live independently. There are certain filarial worms which ordinarily live in moist earth, but which now and again, as necessity arises, become parasitic. As the moisture disappears these worm retreat into depressions where the moisture is longest retained, but should a snail or earth-worm happen in their way they pick out the cavities of these animals and creep into them. In protracted drouths they are parasitic for a corre- spondingly long period, and it has been observed that in such parasitic existence they attain unusual size and produce a larger number of ova than their free-living fellows (Braun, Heller). It may be that the young brood continue in the snail and become completely transformed into parasites, but the original ones, when Animal Parasites. 79 wet weather returns, abandon their parasitic hiding places. L. Oerley has succeeded in artificially causing a free species of worm (rhabditis pellio) to live temporarily as parasites by introducing them into the vagina of mice, where they continued to live and multiply, although when placed in the digestive canal they died or were expelled. Larvae of flies often resort to parasitism as oppor- tunity is afforded; meat flies and other insects which are ordinar- ilv saprophagous often oviposit upon some animal in wounds or ulcers and the resultant maggots obtain their nutrition in the same location as parasites, although succeeding generations con- tinue as usual under other conditions of existence. It may be supposed that frequently such assumptions of a parasitic existence are brought about by the force of circumstances and end with the death of the organism if it be incapable of adaptation, even if it should succeed in getting nourishment from the body of the ani- mal host. Only in case the intruding worm (or other form of life) can successfully withstand the mechanical and chemical influ- ences which oppose it, only in case it obtains a habitat where it is possible for it to live, is it likely to be changed into a parasite. Some worms may be -parasitic in different animal species; trichinella is parasitic in man, hog, rat, mouse, cat. fox, polecat and bear, and may be artificially induced to infest the dog, rabbit, guinea-pig, sheep, horse and other mammals. In the same way the liver fluke is found in a number of species. Other parasites, on the contrary, occur in only one fixed species. For example, tcenia solitmi and tcciiia saginata are found only in the human intestine; crassicolis only in the cat ; in the intestine of another species they die and it is impossible or only an exceptional case that they should persist. Such exceptions, however, do occur naturally as well as in artificial attempts to infest. For example, bothrioce- phalus latns, whose normal host is man. is occasionally found in the intestine of the dog; echynorhynchus gigas, a parasite of the intestine of the hog, is in rare instances met in man. Such cases are to be explained by exceptional opportunities for transmission. The influence of parasites upon the host varies much accord- ing to their habits and situation. In many instances the presence of a parasite occasions no noticeable disturbances ; dogs may have dozens of tapeworms in them without showing any evidence of sickness, although in other cases even a small number of the same tapeworms cause digestive disturbances. At one time it was sup- posed that some parasites were of use to the host, as the larvae 8o Causes of Disease. of one of the gastric flies (j^astrophilus sahttaris — so named from this idea) ; it was thought that their presence in the stomach and small intestine of the horse promoted the secretion of gastric juice ; or it was believed that some parasites consumed superfluous mucus. Although it is reasonable to suppose that some parasites obtain their nutriment from the waste matter (as is true of the infusoria and bacteria always present in the stomach in rumi- nants) and take part in the breaking up the intestinal contents, yet it is not to be concluded that the parasitic worms and arthro- pods have any value whatever to their host. On the contrary, the animal host, if rid of them, will tlirive equally and better. All parasites exert from time to time some harmful influence, and some are death-bearing guests. In the first place, many parasites are harmful to their host and productive of' disease by their wandering in the body and their movements. Undoubtedly the itching caused by the crawling para- sites inhabiting the skin-surface, and often giving the host no rest day or night, has some influence upon the health ; here may be mentioned the sheep-lice, itch-mites and the oxyurides inhabit- ing the rectum and causing continual tickling sensations, as per- fect torments which often give rise to emaciation (due to the in- crease of metabolism following the incessant restlessness from the itching). Other parasites make their way through the tissues by boring, and thus where any considerable number penetrate into the organs cause tissue destruction and occasion haemorrhages and inflammatory lesions (lesions produced by liver flukes, larval tape- worms and lingiiatulidse). They may give rise to a great variety of disturbances, just as any foreign bodies in a mechanical way, by compression of tissues, or by obstruction and narrowing of tubular passages, as sudden death by invading the brain, paralysis by pressure on the s])inal cord, atrophy of the liver by growth in its parenchyma, blindness by penetrating into the eye, rupture or thrombosis of the larger blood vessels, respiratory interference and suffocation by lodgment in the air passages and lungs, and intesti- nal obstruction. The parasites adhering to the intestinal mucous membrane by booklets or suctorial apparatus often produce re- flexly marked irritative or perhaps nervous phenomena ; and, too, a toxic influence is to be ascribed to the metabolic products of a number of worms which may be reasonably thought to explain the occurrence of nervous changes and general loss of flesh (as in Animal Parasites. 8i case of echinococcus cysts, bothriocephalus and teniae*). Local inflammatory lesions of the skin and mucous membranes are the result of mechanical injuries caused by a variety of parasites. The amount of nutritive substance abstracted by parasites from the host is to be regarded as usually relatively insignificant. Where, hov/ever, the parasites are blood-suckers, the host is placed at special disadvantage ; the smallest of the round worms, if pres- ent in large numbers, may cause serious loss of blood, and per- haps the death of the host. The roe. the common deer and the sheep, for instance, are uniformly killed by an anaemia if blood- sucking strongylidas infest the rennet-stomach. Whole flocks of poultry mav die out when the poultry mite, dcrmanyssus avium. gets into the hennery and infests the skin of the fowls in vast numbers, feeding daily upon the blood. A century ago our appreciation of the life history of the parasites and of the diseases caused by them was but vague. It is true that most of the worms found in the human alimentary canal were known to the students of natural history in antiquity: and as early as the seventeenth cen- tur>- itchmites and their relation with the itch were fairly well known. Yet it was for the most part believed that parasites had their origin in inspissated juices or pathologically altered parts of tlie human or animal body by a process of spontaneous generation (gcncratio ccqutvoca). When the microscope came into use and it became possible to closely observe their generative organs and their products (eggs), and particularly after attempts came to be made to artificially transmit the parasites by experimental feed- ing of the worms and their larvc-e, the real history of their development was for the first time apprehended. Redi and Swammerdam, van Doeveren and Pallas, Pastor Goeze, C. Fr. Miiller, Bojanus, Abildgard, toward the end of the i8th and the beginning of the iQth century, Steenstrup, v. Baer, V. Siebold, van Beneden, Kiichenmeister, in the middle of the latter century, corrected the mistakes and hiatuses of the earlier views and investigated the most interestmg parasites ; and in recent years the studies of a large number of zoologists, physicians and veterinarians (Leuckart. Zenker, M. Braun, Peroncito, Grassi, Railliet, Heller. Ziirn. L. G. Neumann. V. Ratz and others) have contributed to extension of our knowledge in this field to such a degree that pathology and practical hygiene have been decidedly benefited by their investigations. ♦Persons handling ascaris megalocephala, the rouud worm of the horse, es- pecially if engaged in mincing it, are apt to be directly affected by a conjunctivitlB .-■nd lu-ticarial eruption frrmn a certain substance cxistinrr in the cu.tlcle of tho worm (apparently a dermal secretion) which possesses irritative properties. 82 Causes of Disease. TABLE OF PARASITIC ARTHROPODA OF THE DOMES- TIC ANIMALS.* I. Insects {Insecta). 1 — Blood-sucking Flies, attacking- the Skin. (After Neumann.) Culex pipiens (and other gnats) in man. Simulia reptans, horse ; mucous membranes of the head, " maculatuin, horse, ruminants, man. Tabanus hovinus, morio, aiitiimnalis, bromiiis, nisticus, fulvus, albipcs, horse, ruminants, man. Hcpmatopota pliiznalis, horse, ruminants, man. Chrysops cacutiens, horse, ruminants, man. Stomoxys calcitrans, horse, Hamatobia stimulans, fcrox, irritans, serrata, horse, ruminants. Glossina morsitans, horse, ruminants. Hippobosca equina, horse, ruminants, dog. Mclophagus oz'iniis, sheep. 2 — Flies Parasitic Upon or Beneath the Skin in Larval Stage. Calliphora oomitoria, various domestic animals. Sarcophaga carnaria, magnifica, JJ'ohlfarti. Liicilia Ccusar, sericata, maceUaria. Ochromyia anthropophaga, dog, cat, goat, man. Hypodcrma lincata, sheep [cow]. " tarandi, reindeer. " hovis, cow (even in the spinal canal). " silenus, horse, ass. Dermatobia noxiaUs, cow, dog. 3 — Flies Whose Larvae are Parasitic in the Intestines and Body Cavities. Gastrophihis eqiti, stomach and pharynx of [horse] . " pecorum, stomach. " diiodcnalis, duodenum of horse and exceptionally in dog. •Details of the life-history and the patholog-ical significance of the species enumerated may be found in Kitt's "Lehrhuch der Spesiellen, Pathol. Anatomic der Haustiere." [See also I'riedberger and Frohner, Veterinary Pritholonii, Amer. Edition, 'W. T. Keener & Co., Chicago, 1904.) Animal Parasites. 83 Gastrophilns hcomorrhoidalis, stomach, rectum of horse. " flavipes, stomach of ass. Oestrus ovis {Cephalomyia oris), nasal and brain cavities of sheep. 4 — Fleas. Pulcx irritans, man, dog, cat. " serraticeps, dog. " goniocephalus, rabbit. " avium, chickens, pigeons and other birds. penetrans, sen Sareopsylla penetrans, man, domestic ani- mals (tropical). Sareopsylla gallinaeea, domestic fowl in tropics. 5 — Lice. Hccmatopinus macrocephalus, horse. " eurysternus, cow. " tenuirostris, cow. " steiwpsu, goat. " cameli. camel. " piliferus, dog. " latus, dog. " ventricosus, rabbit. 6 — Parasites of Hair and Feathers. Trichodcctcs pilosus, horse. " panimpilosits, horse. " scalaris, cow. " spharoccphalus, sheep. " climax, goat. " latus, dog. " suhrostratus, cat. Melophagus ovinus, vid. blood-sucking diptera. Goniodes dissimilis, Burnetii, Gonioeotes hologaster, gigas, Lipcurus variabilis, hetcrographns, Mcnopon pallidum, biseriatum, all in the hen. Goniodes stylifer, polytrapeaius, Menopon biseriatum, turkey. Goniodes nnmidianus, rectangulatus, Lip. numidice, Menop. numidice, guinea fowl. Goniodes falcicornis. parvieeps, rectangulatus, Menop. phcBOS- tonium. horse. 84 Causes of Disease. Goniodes colchicus, truncatus, chrysocephalus, Lipeurus varia- bilis, Menop. productiim, biseriatum, pheasant. Goniodes minor, compar, Lip. bantlus, Colpoceph. longicaudum, Men. lainm, biseriatum, pigeon. Docophorus ict erodes, adustus, Lipeurus jejunus, anseris, Trino- ton conspiircatum, continuum, goose. Docophorus icterodes, squaUdus, Trinotum luridum, Menopon obscurum, duck. Ornithobius bucephalus, swan. II. Spiders. (Arachnoida.) 1 — Mites. Parasites Upon the Skin. Demodex sive Acarus folliculorum canis, cati, suis, caprce, ovis, etc. (in the sebaceous glands and hair folHcles). Sarcoptes major s. scabiei communis, in and beneath the epi- theHum, in horse, dog, sheep, goat, camel, monkey, man. Sarcoptes minor, cat, rabbit. Dermatocoptes communis, horse, cow and sheep ; also in goats. " cuniculi, in ear of rabbit. Dcrmatophagus communis, horse, sheep. " auricularum felis, cat. " " canis, dog. " " cuniculi, rabbit. Dermatoryctes mutans, fowds, foot itch. Sarcoptes lavis, pigeons and fowds. Epidermoptes bilobafus and bifurcatus, fowls. HarpirhyncJius nidulans, pigeons, in the feather follicles. Hypodcctes columbarum, pigeons, subcutaneous connective tis- sue and body cavities. Laminosioptes cysticola, fowls, connective tissue. Cystodites nudus, fowls, pheasants, air spaces, lungs, liver, kidneys. Syringophilus bipectinatus, fowls, pigeons. '■ uncinatus, peacocks, quills of feathers. Analges minor, fowls, quills of feathers. Dimorphus columbce, pigeon. Leptiis autumnalis, dog, man. Dermanyssus avium, birds, man, dog. cat, horse, cow (ear). Gamasus ptcropoides, rabbit, mole, field mouse, cow (ear). Cheyletus parasitivorox, rabbit. Animal Parasites. 85 2 — Ticks. (Sucking blood from skin.) Ixodes ricinus and hexagomis, man, dog, horse, cat, ruminants, birds. BoopJiilus annulatiis s. bozis, cow (America). Dermacentor reticulatus, sheep, cow, horse, man (America). " clectus, dog (America). Argas miniatus, cow^ Amblyonima americanum, cow% man. Ornithodorus Mcgnim, man, cow, sheep, horse, ass, dog. Argas reflexns s. marginatus, pigeons. 3 — Pentastomes of the Viscera. Linguatula tcenioides, dog, wolf, horse, goat, man (nasal pas- sages). Larval form, Linguatula denticulata (mesenteric lymph nodes, lungs, liver), ruminants, horse, cat, rodents. LIST OF WOR^IS PARASITIC IN THE DO:\IESTIC ANIMALS. I. Flatworms. 1 — Tapeworms. Anoplocephala s. Tccnia plicata, horse. perfoliata, horse. " mammillana, horse. Moniccia cxpaiisa, ruminants. : i planissima^ ruminants. " Benedini, ruminants. " Neumanni, ruminants. " trigonophora, ruminants. " denticulata, ruminants. " alba, ruminants. TJiysanosoma ortinoides, sheep. " Giardi. cow and sheep (hog). Sfilcsia ccntripunctata, sheep. globipuuciata, sheep. Tcriiia nwrginata. dog; bladder worm, cysticcrcus tenuicolUs, ruminants and hog. Tccnia scrrata, dog; bladder worm, cysticcrcus pisiforniis, hare, rabbit. 86 Causes of Disease. TcEtiia echinococciis, dog, jackal, wolf; bladder worm, echinoc- occiis polymorphns, man, ruminants, hog. Tceriia canurus, dog; bladder worm, co'nurus cerehralis, rumi- nants, horse. Dipylidium caninum^ (Taenia cucumerina), dog, cat, man; bladder worm, cryptocystis tricJiodectis et pulicis, larvae of dog fleas and ticks. Mesocestoides lineatus (Taenia litterata), dog, fox, cat. Tcenia serialis. dog ; bladder worm, cysticercus s. coenurus seri- alis, rabbit. Tcenia Krabhei, dog; bladder worm, cyshcerciis tarandi, rein- deer. Bothriocephadus lotus, man. dog, cat ; larva, plerocercoid of fishes. Bothriocephalus cordatiis and fusciis, dog. Tauia crassicollis, cat ; bladder worm, cysticercus fasciolaris, mouse. Dipylidium Chyzeri. PasquaJi. Trinchcsii, cat. Tcenia solium^ man ; bladder worm, cysticercus ceJluloscB, hog, dog, cat, sheep, roe, polar bear, rat, man. Tcenia inerniis hoin. s. niediocanellata s. saginafa, man ; blad- der worm, cysticercus inerniis, cow. Drepanidiotccnia inf undihulif orrnis , fowl. Dicranotcenia sphenoides, fowl. Davainca proglottina. " tetragona, eesticillus ectinohothrida, fowl; Fried- bergeri, pheasant. Bothriotcenia longicollis, fowl. Drepanidiotcenia lanceolata, setigera, fasciata. anatina, gracilis, Krabhei, tenitirostris, goose and duck. Dicra>iotcenia furcigera, megalops, eoronula, duck. Mesocestoides inibuti[ormis, duck. Echinocotyle Rosseteri, duck. Dazainea crassnla, pigeon. Bothriocephalus colunibarum, pigeons. 2 — Fluke-worms. Fasciola hepatica. distoniuni hepaticuni, rtmiinants, hog, ass, horse, rodents, man (liver — errant examples in the lungs and musculature ). Animal Parasites. 87 Fasciola laiiccolata, distoimim s. dicrocceliiim lanceolatum, ru- minants, hog, rodents (liver). Fasciola magna, cow, elk [deer], (liver), (America, Italy). Distomum truncatum, alhidiim and felineum, cat (liver). Agamodistomiim snis, hog (muscle). Distomum, echinostomum alatum, ducks and other water fowl, exceptionally dog (intestine). Amphistoma conicum, ruminants (first stomach). " Collinsi, horse (intestine), (Egypt). Gastrodisciis Sonsinoi, horse (intestine), (Egypt). Monostoma verrucosum, duck, fowl, goose. " attenuatum, goose (intestine). Distoina oxycephalmn, duck, fowl, goose (intestine). " dilatatum, armatum, lineare, ovatum, commutatum, fowl (intestine). Holostoma erraticum, duck (intestine). Distomum hcematohium s. crassum (Bilharsia crassa), cattle, sheep, monkey (urinary organs, intestine), (Mediterranean bor- ders), Distoiiiuiii Westermanni, cat [man] (lungs). Distomum heterophyes, dog (intestine), (Japan). Distomum pancrcaticum, cow, sheep, (Japan). TI. Round Worms. 1 — Acanthocephalid Worms (Thorn-headed worms). Echinorrhynchus gigas, hog, man (intestine). " polymorphus, goose, duck (intestine). 2 — Common Round Worms. Ascaris megalocephala, horse, ass (intestine). " mystax, dog, cat (stomach, intestine). " lumhricoidcs, man (intestine). " suilla, hog (intestine). " vitidi, cow (intestine). ■' " ovis, sheep (intestine). Hctcrakis uujculosa, pigeon (intestine). " inflexa, fowl, turkey (intestine). " papulosa s. vesicularis, fowl, peacock, guinea fowl, turkey (intestine). Heterakis diffcrens, fowl (intestine). " dispar, duck, goose (intestine). Gnathostoma hispidum, hog (stomach). 88 Causes of Disease. 3— Pin Worms. O.vyuris 7 cniticiihiris, dog. man (rectum). ciirvula, iiiastigodes, horse (colon and rectum). ambigua, rabbit (caecum). 4 — Strongylus Worms. Eustrongylits gigus, dog, horse, cow (kidneys, peritoneum, heart, hver). Etistrongylus tubifc.x, duck (intestine). Strongylus anuafus s. sclcrostomuui aruiatuui, horse (intes- tine) ; peritoneum (larvaj and embryos wander into the arteries, brain, testes) ; str. arniatus has recently been subdivided by Sticker into three species: Sclcr. edentatum, hidentatum, quadri- dcntatum. Strougylus tctracaiitJius (sclerosf. tctr.), horse (large intes- tine). Strongylus contort us^ ruminants (abomasum, small intestine). Ostertagi, cow, sheep, goat (abomasum). Ciirticci, cow, sheep (abomasum, small intestine). oncophorus, cow (abomasum, small intestine). Harkeri, cow (abomasum). rctortcrformis, ruminants, hare, rabbit (abomasum, small intestine). * Strongylus lilicollis, sheep (small intestine). radiatus, cow (small intestine). inflatus, cow (colon). .-I.vci. ass (stomach). Iiypostoiuus, sheep, goat (intestine). filar ia, sheep, goat, fallow deer, red deer (bronchi, lungs). Strongylus parodo.vus. hog, sheep (bronchi, lungs). coin.niutatus, sheep, goat, hare (lungs, bronchi). micrurus, cow, horse, red deer, fallow deer (bron- chi, lungs). Strongylus Amficldii, horse (lungs). sagittatus, red deer (lungs). capillaris, goat, sheep, chamois (bronchi, lungs). den tat us, hog (large intestine). " ruhidus, hog (America). annidatus {Strong, s. Filaria tracheo-hronchialis) , dog (air passages). A III III a I Parasites. 89 Strongylus vasoruin canis, dog (blood vessels). " pussihis^ cat (lungs). " tenuissimiis, horse (stomach). " Icporum, hare,, rabbit (stomach), (America). " tenuis, goose (caecum). " nodularis, goose (pharynx). " s. Syngamus trachealis, hronchialis, fowl, pheasant, horse, goose, duck, etc. (air passages). Dochinius trigonoccphahts, dog, cat (intestine). stenocephahis, dog (intestine). " tubceformis, cat (intestine). " boz'is s. CEsophagostoma vcsiculosuui, cow (intes- tine). CEsophagostoiiia colninbiaiiuin, sheep, deer (intestine). Uncinaria cernua, sheep, goat (intestine). Olhdanits tricuspis, cat (stomach, embryos in the lung). Strongyloides intestinalis s. Anguillula stercoralis, man, fowl (intestine). Anguillula vivipara, horse (colon). Rhabdoncnia longum, sheep, hog (intestine). 5 — Whip Worms. Tricocephaliis dispar, man, dog. " affinis, ruminants (large intestine). " crcnatus, hog (large intestine). " depressiuscitliis, dog (large intestine). Trichosoina ccropliUnm. cat (trachea, bronchi). fclis cati, cat (urinary bladder). longicoUc, fowls (csecum and rectum). " aniiulotnrn, fowls (pharynx). " coiitortnin, duck (crop, pharynx). " collar e, fowls (intestine). " tcnuissiiiiiiiii and brevicoUc, pigeon (small intes- tine). Trichina spiralis, hog, rat. man, all carnivora (intestine, em- bryos and undeveloped trichinelke in muscle). 6 — Filariae. Filaria papulosa s. equina, horse (peritoneum, pleura). tercbra, cow, deer (peritoneum, eye). 90 Causes of Disease. Filaria lacrymalis, horse, cow (conjunctival sac). " imniitis, dog (heart) (Asia [America]). " s. Spiroptera sanguinolenta, dog (stomach, aneurisms, pharynx). Filaria s. Spiroptera strongylina, hog (stomach). " s. Spiroptera megastoma and microstoma, horse (stom- ach) ; Gongylonema scutatiim, sheep, cow, horse (pharynx) ; Gongylonema pulchrum, hog (pharynx, tongue). Filaria s. Onchocerca reticulata, horse (tendons, ligamentum nuchse). Filaria hceniorrhagica, horse (skin). DermoHliaria irritans, horse (skin). Filaria uncinata, goose (pharynx, crop, intestine). " nasnta, fowl (crop). *' s. Dispharagits spiralis, fowl (pharynx, crop). Tropidocera inflata, duck (crop). 7 — Annelides. Hcemopis sanguisuga, horse (pharynx). COURSE AND TERMINATION OF DISEASE; SYMPTOMATOLOGY; DIAGNOSIS The disturbances of function which indicate the existence of disease, as well as anatomical or chemical organic changes, are spoken of as the signs or symptoms of disease; the branch of study dealing with these as semeiology or symptomatology {t6 <7r),xdov from ai)iJ.aivui, to denote ; (Jv^x-lvl^^TeLv, to happen with, that is, in connection with certain disease states).* The art of concluding from symptoms the existence of definite morbid changes in the body, of determining the nature and loca- tion of disease, is known as Diagnosis or establishment of a diagnosis (i, d^dy,u,^is, differentiation or thorough knowledge; from 7a•"i'T^-«^ ^o recognize). Formerly when the anatomical and chemical faults which underlie disease were unknown it was deemed sufficient for the physician to merely appreciate the ex- ternal manifestations of disease, and such terms as dropsy, jaun- dice, fever and marasmus were used without attempt at nearer approach to the causes of these symptoms. Even to-day there may now and again be times when it is necessary to rest satisfied with no more than such a symptomatic diagnosis. However, as far as it is possible to conclude from symptoms that definite ana- tomical changes exist, or as far as such are directly manifest, we are accustomed in these days to make anatomical diagnoses; and as far as it is possible to determine the development of any aft'ection, to make also an (etiological diagnosis. The aim of modern diagnosis is the study of the disease from all three of these points of view and the appreciation of the condition of all the organs in their relation to each other, so as to permit of the recognition of how a given local condition must influence the rest of the organs of the body generally. 'The prlnclpaT features of tbls chapter have been In Part adapted from Handbuch der aUgem. Pathologie, Fhl und Wagner (Leipzig, 1870). 92 Symptomatology; Diagnosis. A purely symptomatic diagnosis is illustrated by such examples as the determination of varieties of convulsions, of palpitations, coughs ; a symptomatic and anatomical diagnosis, by the recognition of a relation existing between jaundice and some hepatic affection; an ^etiological diag- nosis, by the conclusion that a jaundice depends upon the presence of some microorganisms in the liver and blood. [Very frequently diagnoses are classified as topographical, when indicating the location and extent of lesions, and as nosological, when indicating the nature of the process. No diagnosis can be regarded as complete unless embodying the recogni- tion of both location and nature of an affection, as well as of its aetiology, in so far as is possible. Incomplete, purely topographical diagnoses, as the declaration of "lung disease," "kidney disease," etc., are often made to serve the nonce, or by the careless as final ; in the same way an incomplete, merely nosological diagnosis is often met with where it is said that an individual is the subject of "inflammation," "congestion," "dropsy," "fever," "tuberculosis." The full diagnosis should declare that the subject has an inflammation of the pericardium, if possible indicating the cause of the pericarditis ; "tuberculous caseation of the lungs" would embody all the desirable points of view.] Symptoms immediately referring to changes in a given part, as abnormality of color, increased size, hardness, softness or un- evenness of outline, are spoken of as direct symptoms; those which do not depend upon the diseased organ entirely, but which perhaps may be appreciable in the products of such an organ or become manifest in other organs in relation with the diseased part, are known as indirect symptoms. Thus a direct symptom of a lesion of one of the cardiac valves would be a cardiac mur- mur ; an indirect symptom of pericarditis would be an oedema of the dewlap. There are certain symptoms called pathognomonic sympfouis, whicli definitely indicate the existence of some particu- lar disease, as the rusty nasal discharge in pneumonia, locking of the jaws in tetanus, crepitus at the site of a fracture of bone; however, as a rule a single symptom does not suffice for a diag- nosis, but must be considered in its relations with a wider group of recognized features. Study of disease phenomena constitutes a large part of clinical pathology and pathological anatomy; tho ability to recognize and to determine the im.portance of symptoms is one of the essentials of the medical art. and depends on the skill, experience, general knowledge and power of judgment of the individual conducting the examination of the subject. The majority of symptoms can be realized only by special methods of examination. He who has not acquired such methods cannot have a clear understanding about the morbid condition extant in the body of his patient, and is really groping about in the dark- f j Diagnosis. 93 ness. Eye, ear and sense of touch, partly unaided, partly aided by instruments of precision and special technical methods (em- ployment of reflecting mirrors for illumination, of instruments used in percussion and auscultation, of methods of mensuration, weighing, thermometry, microscopy or chemical tests) contribute to our power of appreciation of the signs of disease. With ex- perience it is possible that the examiner at a single glance (diagnosis at a distance) may recognize some types of disease, some forms which manifest themselves by sharply marked ex- ternal features appreciable even at a hasty inspection. Other morbid conditions may be more or less correctly conjectured from the information given by some person from his observation of the patient (diagnosis from the aiiaiiiitcsis: ava-ixifj-vriffKO}, to recollect). Both methods are open, however, to serious error if practiced alone, being based on incomplete data and imperfect in- vestigation ; and although practical experience with quick per- ception of frequently observed facts may often arrive at the truth by such methods, only careful objective study will guaran- tee an absolutely certain diagnosis. In order to gain a compre- hensive idea of the pathological process presented, it is essential not only to consider the functional disturbances of one single part of the body, which is apparently the seat of the disease, but to systematically inquire into the condition of every part of the economy and every function. (For fuller discussion of these points the reader is referred to Friedberger-Frohner. Lchrhncli dcr kliiiiscJicii Unfersiicliuiigs- methodcn, or ^loller, Klin. Diag. dcr dusscni KraiikJicHcii dcr Haitsticrc. F. Enke, publisher.) The art of diagnosis concerns itself, after the proper recog- nition of the symptoms manifested, with the condition of the oreans, finallv reaching a definite conclusion through processes of comparison of the features appreciated with the commonly ac- cepted pathology of known diseases. All possible affections are carefully considered, the symptoms presented by the subject con- trasted wath those of each different known disease, and determina- tion of the aft'ection attempted from the strongest features of correspondence. [In systematic study of a given case it is well to follow some routine of investigation. Thus commonly one takes into consider- ation such general features as the age, sex, race or species of the subject, the general surroundings and habits of life and features 94 Course of Disease. bearing on questions of heredity; subsequently the general pre- vious medical history of the subject, the anamnesis, is taken up, and a study of the known features of the present attack in its development. Thereafter is made a close and complete objective study of the subject, this including as thoroughly as possible the whole body, the condition of every organ by the methods of ordinary physical diagnosis and the more elaborate methods of clinical technology. Given such data one should be able by his patho- logical training to recognize the seat of the affection and the extent of its distribution in the body, the topographical diagnosis, and the nature of the affection, the nosological diagnosis.] The establishment of a diagnosis leads directly to prognosis and therapeutic application. By the term prognosis is meant the foretelling of the mode of development [the order of the events in the course, and the duration of the disease] and termina- tion (whether favorable, prognosis faiista ; unfavorable, prognosis infansta ; or uncertain, prognosis anccps). The course and ter- mination of many diseases may be predicted with more or less certainty, inasmuch as examples of the aft'ections are constantly occurring and an experienced physician is quite familiar with their development and modes of progress. The prognosis must, however, in a measure depend upon each individual case, its special constitutional peculiarities, the degree of general involve- ment of the bod}' and the distribution of the disease-changes, the vital importance of the affected organ, the variations of the disease from its usual trend, the complications and the possibility of em- ploying proper remedial measures. Therapeutics (i) Oepawela, from eepairevco, to serve or cure) or remedial treatment has to deal with eft"orts directed toward com- pensation for and removal of disease. Where it is possible by definitely conceived measures to remove the basic fault, the anatomical alterations and the causative influence underlying the morbid condition, therapy manifestly becomes rational or radical; where it is possible only to combat symptoms (pain, fever) it is said to be symptomatic treatment, which at best is but a tempo- rary means or measure of relief (paUiative, from pallium, a cloak or protection). The duration and course of diseases depend closely upon their causes and upon the extent and nature of their basic structural alterations. Some diseases are sudden in their onset, last but a few minutes or hours, and terminate in the death of the individual Diagnosis. 95 or in a rapid disappearance of the various lesions. The former type includes such conditions as wounds, lacerations of external or internal parts or the effects of poisons which rapidly and com- pletely destroy the function of vital organs ; the latter, character- ized by rapid recovery, is met in disturbances which are not fol- lowed by structural changes, as convulsions, ansemic and hyperae- mic states of the brain, of the skin and of mucous membranes. On the other hand, diseases may continue for weeks or months, or even years. They may begin suddenly or gradually and insidiously ; may manifest alternately intensity and diminution in the severity of their symptoms, fluctuations in the morbid processes (remis- sions and exacerbations) ; may invade suddenly {paroxysmal; paroxysm, invasion) and present interruptions {intermittent) in the course, sometimes ending with gradual improvement {lysis, resolution) , sometimes in a rapid, abrupt change {crisis, decisive stage), leading to recovery or death. [By the course of the dis- ease is meant the order of manifestation of the various stages or events of the disease. It may be definite, regular or acute on the one hand, when its events proceed in orderly manner and come to a definite termination, or it may be indefinite, irregular or chronic, when there is no fixed order of events and there is no set limita- tion. Among the different types of the regular course two major forms are recognized: (a) the continued course, where there is but little variation in the intensity of the symptoms from time to time, and (b) periodic courses, in which at certain definite times special events manifest themselves. Among the periodic courses are met, intermittent forms, in which there alternate periods of absence of symptoms, known as intermissions, with periods of presence of the symptoms in their intensity or paroxysms ; remit- tent forms, in which there alternate periods of intensity of symp- toms, known as exacerbations, with periods of diminution in in- tensity, known as remissions ; and recurrent forms in which there alternate comparatively long periods of absence of symptoms, the intermissions, with similarly prolonged periods of their presence, recurrences. The last form differs from the first in the length of the alternating periods.] Diseases of brief duration are called acute diseases; those of prolonged course, chronic. The former may last for a variable period, up to fourteen days, while the latter extend over a course of more than forty days : any instances falling between these durations mav be classed as sub-acute affections. In case of g6 Course of Disease. diseases which ordinarily continue for a year or more, a shorten- ing of the course to a few months manifestly fixes such duration as an acute one, as in case of tuberculosis, glanders or rickets. [The terms acute and chronic have really a less, limited signifi- cance than the author here applies to them ; they each have in one sense a reference to the length of the course, but in addition refer, perhaps without desirable clearness, to the possibility of recovery and the intensity of symptoms and the order of events in the course. In the matter of time it is scarcely possible to give any fixed number of days, or even months, to the terms. Each dis- ease is a law unto itself, and only in the broadest way may we say that an acute course is one of brief duration. But in addi- tion, when we apply this term, we mean that whatever the actual duration, at any rate the disease will come to a definite Umit ; and, moreover, w^e expect the course to follow more or less closely a given order in the manifestation of its symptoms, and believe there is a chance of recovery. In case of chronic diseases again we cannot set a fixed limit of days, months, or even years, which shall declare the course to be a chronic one. (Thus, while alienists are inclined to set a limit of a year to cases of mania or melan- cholia, and to call all cases chronic if of longer duration, there really are no appreciable dififerences in many instances of even longer duration from their condition within the first few weeks of insanity.) Moreover, when a case is declared chronic, while there is no actual assertion to this effect, nevertheless there is a feeling of hopelessness as to the chance of recovery ; the termina- tion looked for is rather death, and that at an indefinite time. No exact order of symptom presentation is expected in such chronic cases. Finally, while there are often exceptions to this point, in general the severity of the symptoms of an acute case is apt to be greater than in a chronic form of the same disease.] Diseases often show [especially those of an acute, regular or definite type of course] a succession of definite periods or stages in which certain phenomena appear, which are empirically expected and whose development is awaited with the progression of the anatomical changes. These diseases are said to have a typical course. [A regular or definite course is well illustrated by the acute infectious fevers, in which the following periods may be recognized in the order named: (a) infection (time of en- trance of the microbic cause), (b) incubation (a period without symptoms, l)ut during whicli the .germs are multiplying in the Stages of Disease. 97 economy to sufificicnt number to excite their definite elTects), (c) prodrojiics (a period of indefinite and usually slight symptoms, the first and as yet more or less obscure evidences of the presence of microbes in the system), (d) invasion (the period of develop- ment of tlie specific symptoms of the afifection ; this, if it occur rapidly, is said to be a fnuik iiiiasioii; if gradually, is called an insidious iivz'asioji), (e) acme or fastigium (the period of fullest intensity of the disease), (f) occasionally an amphibolic sta^c (a period of uncertainty and marked variation, corresponding to the popular idea of crisis and used by the author above in this sense), (g) decline (period of disappearance of the disease; this, if it occur rapidly, is said to be "by crisis;" if slowly, "by lysis''), (h) finally, not as a true stage of the disease, but a definite period before health is resumed, convalescence (period of repair and re- building of structures destroyed or impaired in the course of the affection, and of resumption of efficient function by the various parts of the body). If the cause of an acute disease be not a vital one the course includes, of the above stages, only those of invasion, acme, decline and convalescence.] However, in such well-known affections, as a result of special etiological factors or the accidental interference of external in- fluences, variations (irregitlarities) may occur, rendering the course an atypical one. In case the symptoms remain for a long time of uniform type and intensity, without appreciable ameliora- tion or increase, the disease is said to be stationary. Latent diseases are those which do not manifest themselves, either at all or in part, in certain phases of their development. This depends upon either the impossibility or difficulty of proper examination of the organs, which are the seat of the disease (as the pancreas or some parts of the lung), or upon the fact that the disease is so localizefl or has been so gradual in its development that the function of the organ has not been materially affected. Latency is often, therefore, only a temporary or transient feature, and it is often correct to speak of a latent stage and of a later m.anifested or open stage. Some diseases, even though they be severe, remain latent because they are foUowed by adaptations (compensatory conditions) which entirely prevent their usual symptoms, as when a valvular lesion of the heart is followed by compensatory cardiac hypertrophy. When a disease is characterized merely by local symptoms and alterations it is known as a local disease or disease of [this ov 98 Course of Disease. that] organ; if, however, a number of organs are involved and their functions interfered with, and if the general economy is ap- parently affected, the condition is spoken of as a general disease or a disseminated (generalized) disease. (Examples of general disease are met with in such alterations as provoke general metabolic disturbances and abnormalities in the composition of the blood. Formerly the term constitutional disease or dyscrasia, de- composition of the blood, was used in this connection.) Funda- mentally there is no distinction in these terms, but as a rule the term dissemination has special reference to a multiplication of local lesions, to an extension of the causes of the disease to a number of situations where new foci of the same type appear, or to a reaction of a functional disturbance of one organ upon the rest of the system. For example, a prolonged disturbance of the function of the kidneys will give rise to a disturbance in the cardiac action and retention of harmful products of metabolism ; or, as in the case of tuberculosis, the infectious agencies pass from the original local focus into the lymph and blood, extend by direct growth into the surrounding organs, and in various scat- tered foci in the body to which they have been conveyed ; the dis- ease thus becoming disseminated and generalized. Some affec- tions, on the other hand, at first manifest general symptoms (fever), later, however, showing distinct evidence of their purely local type. Variations in the course of disease may also depend upon the predisposition characterizing the animal species in ques- tion, as, for example, is seen in case of glanders in field mice, an acute septicemic affection, in contrast to the same disease in horses, where it is usually a chronic local affection, gradually ex- tending through the system. The local lesions which first arise from the operation of a pathogenic agency are known as primary lesions, those which fol- low as secondary. The action of such an agency may be confined to one locality, the lesions disappearing after its removal, as in case of corrosion, heat action or traumatism. The generalization usually depends directly upon the spread of the pathogenic influ- ences through the body, and may therefore take place (i) by continuity and contiguity of the tissues (per contimdtatem, per contiguitafem) , (2) by the blood or lymphatic tissues {hcematogen- oi!S, lymphogenous), and (3) as already referred to, the func- tional interdependence of one organ upon the others may, in case of disease at one point, lead to further change in other parts of the Extension uf Disease; Termimition of Disease. 99 system {sympathetic or consecutive lesions). By the term exten- sion by continuity is understood the progress of the pathological process upon the surfaces in continuity and along uninterrupted tissues in the immediate vicinity of the original focus, as along the mucous membrane of the nose to the frontal and maxillary sinuses, from the pharynx to the Eustachian tubes and middle ears. Extension by contigxiity occurs from one surface to that of an adjacent organ in contact with the first, as from the. visceral pleura to the costal pleura, from the serous surface of the stomach to the liver. The explanation for such a mode of extension is mainly to be found in the fact that the pathogenic agent finds some particular opportunity for invading such adjacent tissues; thus bacteria may pass to an adjoining structure, be swept along by its fluids and spread widely. A suppurative or gangrenous focus in the lung may in some such manner gain access to the pleura; the latter may rupture and the microorganisms, spread over the entire pleural surface from the respiratory movements, mav give rise to an extensive pleuritis. Hccmatogenous extension of a disease occurs when the pathogenic agents gain access to the blood; IxmpJwgcnous cxtcnsioji. when such influences, through the agency of the wandering cells, are mingled with the lymph (cf. emboHsm). Sympathetic disturbances in function arc appar- entlv in part the result of sensory and motor reflex action, in part the result of primary changes, the etficiency of one organ depending upon the functional integrity of another, as a chronic hepatic cirrhosis induces cardiac hypertrophy and splenic cyanosis by the circulatory disturbances which it produces. Coincidence of diseases may occur entirely independently of any relation between the processes, or may depend upon some connec- tion ; where this occurs complications are said to exist. Thus swine-erysipelas is often complicated by valvular endocarditis (the infectious germs invading the latter structures), o'- suppurative osteitis of the cranium may be complicated by a meningitis (through extension of the suppuration by contiguity to the meninges). The termination of disease may result in one of three ways: 1. Recovery, cure or restoration, complete re-establishment of the disturbed function and condition of the organ ; 2. Incomplete recovery, with appearance of secondary affec- tions, persistence of sequels or defects ; or 3. Death of the individual. lOO Termination of Disease. Tcnniiiation in recovery is accomplished through the repara- tive powers natural to the economy. The body is possessed of a variety of regulative mechanisms, whereby the influence of harm- ful agencies is neutralized, the loss of chemical substances and tissues is repaired, and noxious materials are eliminated from the system. Such processes may in a compensatory fashion correct this or that fault, as by the discharge of toxic matter from the stomach or intestines, the removal of the products of fatigue from the muscles and nerves through the blood and lymph, the expul- sion of exudations from the lungs through expectoration. IVIany corpuscular disturbing factors (as bacteria, dead cells, haemor- rhagic foci) are removed through the activity of the living cells (phagocytes) and digested, the body being thus freed of such sub- stances. Other foreign bodies are encapsulated by a wall formed by the tissues of the organism for their own protection, and thus rendered harmless. Deficiency of nutritive material in the fluids and cells is corrected by the supply from the stomach and intes- tine ; dead cells are replaced by new elements from existing forma- tive areas (as new blood cells from the bone-marrow). Tissue losses are repaired by processes of regeneration. And, too, the production of antibodies of most varied type is possible for the protection of the animal body. The therapeutic art is in no wise at variance with natural proc- esses of recovery, but, on the contrary, employs the various regu- lating and compensatory mechanisms of the body in order to bring about an adjustment of the disturbances, and attempts to induce conditions more favorable to a rapid adjustment than is possible when no influence is brought to bear upon the pathogenic agent ; at the same time it attempts to restrain further agencies which may retard the recovery. The practice of medicine is also directed to guard against the extension of contagious diseases and particularly against the inception of disease, so that in this phase, too, the lofty power of science holds nature in check, which, with- out the aid and skilled intervention of man. would threaten with annihilation, all too soon, the creatures of the earth. The sienifi- cance and success of medical science is particularly impressed upon one when it is recalled how destructive epidemic diseases, which in times past carried ofif millions of animals and men, have in some instances been wholly eradicated, in other instances greatlv diminished. By appreciation of the nature of a varied group of affections, there has come the discovery of efficient methods for Tcriniiialidii iii Recovery: Pcalli. loi their cure and for proph>laxis against them. Of course, no rem- edy has been found for death, the inevitable end of development of' all living beings, and the laws of nature can by no medica- ment, whatever its power, be broken. Yet the skillful use of the means of nature may hold ofif premature death and may assist the injured body to regain its health. Medical art can prevent fatal haemorrhages, it loosens adhesions, cuts away what is unfit, dilates narrow canals, has antidotes at its disposal, can procure rapid evacuation of the bowel or emesis, remove foreign objects from the body, relieve promptly nervous strain, alleviate pain directly, often correct irregularity of cardiac action, reduce dan- gerous temperatures and accomplish a multitude of services with- out which a given disease might well end unfavorably or be protracted over a tedious course. After recovery begins at the close of a general affection, there occurs a period, known as convalescence, the subject still evincing muscular weakness and marked sensitiveness to external influences. [During this period there are taking place various reparative and reconstructive processes in the economy, looking to the restoration of altered and destroyed elements, and, too, functional efficiency is being re-established, and all remaining factors of the previous disease are being finally eliminated from the system.] Recovery is regarded as incomplete where, after a disease has run its course, there persist in the economy conditions preventing normal functional efficiency of the organs or where there is evi- dent some permanent impairment of tissue [sequelcc of disease]. As illustrative of this may be mentioned deformities of bones, cicatricial strictures of canals, kinks of the intestines, pericardial, pleural or other adhesions by bands of connective tissue result- ing from the previous disease, opacity of the normally transparent media of the eye, palsies of muscles and nerves, or the defects left after ulceration or burns. Termination of disease in death (e.vitiis lethalis or letalis, from /t^f7/;;/, death; from Ky)et) forgetfulness, \avedvw to make forget- ful) occurs when the organs which subserve the most important and necessary processes of vitality suspend their function. Inas- much as continuance of life depends in an important measure upon the uninterrupted supply of blood containing oxygen to the medulla oblongata through the action of the heart, underlying which must be recognized the necessity for respiratory movements regu- lating the efficiency of the pulmonary surface in the intake of 102 Termination of Disease. oxygen and output of carbon dioxide, it is essential to accept as causes of death of primary importance, various lesions and func- tional disturbances of the hind brain, the heart and the lungs. These parts are therefore spoken of as the atria mortis. Inhibi- tion of their functions may be a direct result of chemical, me- chanical or electrical influences (as from poisons which destroy or paralyze the nerve cells, concussion, the action of lightening), or may indirectly follow a wide variety of factors interfering with tissue nutrition, metabolism and gaseous interchange (anse- mia, albuminous waste, closure of respiratory passages, elevation or depression of body-temperature, reflex palsies). The more important modes, therefore, by which this or that disease may induce death, are : 1. Cessation of cardiac action, caused by toxic or reflex nerv- ous paralysis of the cardiac ganglia, fatigue and degeneration of the cardiac muscle, cardiac rupture, complete obstruction to the escape of blood from the cardiac chambers (formerly known as e.ritus lethalis per syncopeni, (tw-koitthv, to strike together). 2. Asphyxiation, from interference with intrapulmonary respiratory interchange of gases, obstruction of the lungs or upper respiratory passages, compression of these tubes, spasm or palsy of the respiratory muscles, diaphragmatic rupture (exitus lethalis per suffocationem). 3. Mednllary Paralysis, or paralysis of the respiratory centre in the medulla oblongata, from circulatory interference at the base of the brain, influence of toxic substances upon the nerve cells, concussion of the brain or reflex influences (exitns lethalis per apoplexiain, d-n-owXricraei.i', to strike down). 4. Hceniorrhage, from rupture of important vessels, or ex- travasation of large amounts of blood into the somatic and visceral cavities. 5. Exhaustion, from inanition or consumption (diminished nutrition and exaggerated metabolism, accumulation of fatigue products and poisonous metabolites, auto-intoxication). These modes of death may, of course, complicate each other and may be mutually causative of each other (as when haemor- rhage induces ischsemia of the heart and coronary vessels, with the result of cardiac cessation and at the same time the symptoms of suffocation, due to an anaemia of the medulla). Senile debility, more or less complicated by various diseases, is also to be re- garded as a cause of death (senile marasmus, from ^apaiveiv, to Tcniiiiiatioii in Death. 103 weaken), a natural and necessary termination for each individual cell and for the entire cellular complex. In the individual cell, as well as in all the tissues of the organism of higher animals, changes are continually proceeding which lead to the destruction of the living substance and sooner or later result in the death of the individual. The living multinucleated organism is continually losing cells by their death, the substance of which is eliminated from the economy with the excretory material or is broken up and re-employed by the system. From causes inherent in the organ- ism itself, but at present impossible of clear definition (vid. Ver- worn: Geschichte des Todes ; Allgem. Physiologic) the power of multiplication ceases in the individual groups of cells and organs in varying rates in the different species of animals, and with vary- ing swiftness the characteristics of old age and of death become apparent. Perpetual youth, immortality in the sense of reproduc- tion, always renewing themselves, is possible only for the conju- gated sexual cells (propagation cells), while in case of the somatic elements (and those sexual cells failing of copulation) the vegetal force sooner or later disappears. Whenever the decay of cells of vital importance reaches the grade in which it distinctly interferes with the rest of the economy, the mutual relations of the various parts is disturbed, and death ensues, just as a clock stops when its wheels wear out or are broken. Transition from life to death may occur suddenly (mors subi- tanea) ; the animal falls from its standing position to the ground, becomes unconscious, and for a few moments at most is thrown into convulsions with groaning respirations. Such sudden termi- nation may be noted in death from lightening stroke, sun stroke, rupture of the heart, cerebral concussion, massive internal haemor- rhages or cardiac and cerebral paralysis. In the majority of in- stances, however, death comes on gradually, with the manifesta- tion of characteristic phenomena w'hich' predict the termination of life, and which together constitute what is knowm as the death- agony (t7 ayuvla, the Struggle, death struggle). They include the signs of a progressive paralysis of the nervous and muscular sys- tems, together with those of the disease which causes death. Animals in the agonal state are unable to raise themselves from the ground, usually lie flat on one side, from time to time lifting the head and letting it fall heavily to the ground, with the feet rigidly extended and moved convulsively, at first violently, but gradually more and more weakly. Respiration is slowed and 104 Termination of Disease. labored, deep groaning- respirations following at irregular inter- vals the ordinary shallow breathing. With the appearance of pul- monary oedema, rales, heard even at a distance, are produced by the fluid exudate beaten into a foam in the air passages (death rattle). Involuntary discharges occur from the bowel and blad- der, when paralysis of the sphincter muscles develops. The heart beats more rapidly, but the relaxed arteries are no longer able to propel the blood forward and the pulse in consequence, although quick, grows small and finally indistinguishable, and the skin i? cool. The hair is bathed with a clammy sweat. The body tem- perature in the agonal period in diseases accompanied by loss of blood or inanition falls considerably below normal (hypothermia, to 36-35° C), while in other types there may be an ante- mortem rise in temperature. Extinction of life means complete cessation of metabolism, of cellular growth and the existence of the individual ; and death therefore manifests itself by complete termination of the functions of all parts of the body. The last breath, naturally in the form of expiration, and the moment of complete cessation of the heart may ordinarily be looked upon as marking the actual end of life. However, the organs do not all perish at precisely the same moment; after the last breath the heart may flutter a few minutes ; and after death from haemorrhage, peristaltic movements of the intestines may sometimes be ob- served for perhaps fifteen minutes ; and similarly after death from electricity muscular contractions may be elicited as long as rigor mortis does not set in (one to three hours after death). The following are the characteristic signs of true somatic death : 1. Muscular rigidity {rigor mortis), sometimes setting in im- mediately after death, sometimes only after four to twenty hours later, and depending upon the coagulation of the muscle albumen. The muscles in this change become set, shortened and thickened, as in vital contractions ; the extremities are rigid and either cannot be flexed or only with the application of considerable force, and the mouth cannot be opened by ordinary traction upon the lower jaw. After twenty-four hours, or perhaps later, the rigidity disappears [due to decomposition]. 2. Cadaveric fall of temperature (algor mortis) develops in from half an hour to twenty-four hours after death, varying with the surrounding temperature and the degree of metabolic activity prevailing at the time of the death agony. In some affections, as in tetanus, because of the important heat production caused by the Signs of Death. 105 muscular contractions and because after death heat dissipation falls on account of the cessation of the circulation in the peri- phery of the body, a post-lethal internal temperature rise, to perhaps 42-44° C, occurs, persisting a number of hours. 3. The eye in death: The eyelids of the cadaver are usually half open (rigidly) ; the ocular bulb is sunken and somewhat less tense than in life (evaporation of some of its fluids) ; the cornea becomes dull and opaque ; the pupils are dilated. The ocular reflex movements upon touch are entirely absent. 4. Appearance of putrefaction: The bacteria in the digestive tract, producing all sorts of fermentative changes in the contents of the canal, shortly after the death of the tissues, penetrate the latter and cause their putrefaction. The gases, produced in large quantities from the fermentative processes, dilate the stomach and intestines, causing abdominal distension, sometimes to such a degree as to force the lower bowel out of the anus, rupture the diaphragm and allow the intruding intestines to distend the chest. The advance of putrefaction may be noted in the colorless parts of the skin by greenish discolorations (sulphur compounds of haemoglobin), and also by the foul odors of cadaveric decomposi- tion. These changes cause the disappearance of the rigidity of the body and progress the more rapidly the warmer the surround- ing temperature. Measures which inhibit the growth of the putrefactive bacteria, preservation in alcohol or formaline (injection of the vessels with antiseptic or balsamic substances), refrigera- tion, drying, prevent putrefaction. With the advance of putre- faction all the organic matter of the body is broken up into ammoniacal compounds, carbonic acid and water, with the forma- tion of a great variety of by-products (putrefactive alkaloids, acids, gas-forming matter, etc.) until finally only the solid calcified bones remain. The name apparent death is applied to a condition in which all the vital functions are depressed to the ^owest possible degree, when only by great care in the examination of the seemingly dead body can there be detected feeble cardiac contractions and occa- sional faint respiratory movements, a condition accompanied by loss of consciousness and sensibility, and by reduction of the body temperature. In recently born animals this condition is seen com- paratively frequently, lasting perhaps for hours (asphyxia neona- torum) ; in this connection it is perhaps due to a premature separa- tion of the placenta, aspiration of the amniotic fluid, compression of the umbilical cord, or to anaemia. DISTURBANCES OF CIRCULATION Life and health are possible for the organs only if there be unimpaired circulation of a blood capable of supplying oxygen and nutrition to them. Disturbances of the circulation, as well as faults of the blood and lymph, in other words, deficiency in the provision and passage of good blood through the organs, endanger both life and health. The normal heart possesses a notable adaptabilty to the varying demands upon its capacity for work ; it accommodates itself im- mediately to the current of blood entering it by virtue of the elas- ticity of its walls ; regulates the energy and rhythm of its contrac- tions in conformity to the amount of blood in its chambers, the general circulatory resistance and the demand for blood in the ac- tive or resting organs. This power of accommodation enables it, to a certain extent, to overcome and compensate for pathological dis- turbances affecting the hasmic circulation ; under such circumstances there is said to take place a compensation for these disturbances. Where such conditions of resistance to the heart's action are of slow development and permanent, a thickening of the myocar- dium is assumed in connection with the increased requirement for work, consisting essentially in an increase in the number and size of the muscular elements (cardiac hypertrophy). It may be said that even physiologically the size and muscular strength of the heart are adjustable to the demands made upon it in its function as a forcing-pump or as a suction pump. Certain animals, for example, which in the course of their lives perform especially intense muscular work, are likely to exhibit hearts larger in pro- portion to the body-weight than animals accustomed to but little muscular activity."*- Pathological hypertrophy differs from this physiological form only in its cause, in the latter the excessive work being but a natural and customary condition in the life of the animal, in the former the result of abnormalitv of the vascular ►See also Kitt, Lehrbuch der patliol. Anatomic d. Haustiere. II. Aufl. Cardiac Hypertrophy. 107 system, of excessive blood pressure and of unusual quantities of blood within the organ. Such 'Svork-hypertrophy" of the gen- eral organ is met in connection with epicardial adhesion to the parietal pericardium, compression of the base of the heart from pleuritic adhesion, tumors or similar conditions, because in such cases the propulsive effort of the entire organ has a greater oppo- sition to overcome. Hypertrophy of one side of the heart is seen especially in case of valvular lesions. These valvular lesions involve irregularities in the closure of the orifices of the heart and its great vessels ; they are of two types, either narrowing of the orifices from pro- liferative changes, bloods clots, etc. (stenosis), or incompleteness of closure of the orifices by the valves {valvular insufficiency). Stenosis at the aortic opening increases the work of the left ven- tricle in order that the blood may be forced through the narrowed orifice, and in proportion there ensues a work-hypertrophy of the left ventricular wall. Following stenosis at the origin of the pul- monary artery there occurs a work-hypertrophy of the right heart (sometimes dilatation after special preceding strain). X'alvular insufficiency also leads to hypertrophy, because where the valves are incompletely closed there first occurs a tendency to stasis because of the back pressure of the blood (regurgitation), which is likely to induce ventricular or auricular dilatation, and therefore the heart is required to work the harder in order to propel the larger quantity of blood. Although the so-called compensatory hyper- trophy of the heart does in some measure contribute to the regula- tion of the blood distribution and is of some service, yet in reality it is only the expression of an increased blood-pressure in one of the ventricles or auricles or in the aft'erent or efferent vessels, and the compensation which it induces is only a relative one. As a matter of fact, the increase of pressure persists and the circulation does not become normal (Krehl). Even when the animal is at rest the continued heightened blood pressure causes the develop- ment of dilatation of the capillaries, pulmonary passive congestion and distension with consequent diminution in the pulmonary excur- sion, together with difficulty in breathing. The arteries show dis- tinct changes of the pulse, the vessels being unusually tense and distended ; they eventually lose their elasticity and may rupture. A very large heart may in addition mechanically interfere with the lungs. These consequences are still more evident if the indi- vidual exercises physically, the muscular exertion raising the blood io8 Disturbances of Circulation. pressure still higher. (Powerful muscular contractious force larger amounts of blood into the right heart ; the ventricles become engorged and the hsemic pressure rises.) Eventually the heart loses its force as a pathological hypertrophy is not, as might be sup- posed from the thickness of the walls, capable of indefinite response to increased functional demands, but on the contrary, is often unable to accomplish even the more moderate requirements made upon the strength of the heart. Perhaps the reason for this is that the influences which give rise to cardiac hypertrophy at the same time harm the myocardium in other respects. For example, valvular lesions, causing the heart to become hj'pertrophied in their train," are frequently caused by infectious substances. Such agencies may also cause a myocarditis; and if the inflammation be protracted and of low grade, it causes considerable reduction in the efficiency of the muscle. Moreover, the conditions which cause pathological cardiac hypertrophy are typically not stationary, but on the con- trary the circulatory difficulties are apt to progress (the stenosed orifices are likely to become still more narrowed, thrombi which interfere with the vascular lumen become larger, capillary areas become contracted) ; and from such extra demands upon its ability the heart becomes fatigued. There must eventually, therefore, suc- ceed upon compensatory hypertrophy a period of failure of com- pensation, a period of broken compensation. [There are numer- ous influences which combine to limit cardiac hypertrophy* and to determine its eventual loss of compensatory power, and so certain and uniform are these results that it might well be declared a law that every pathological hypertrophy of the heart must necessarily reach a limit to its enlargement and must thereafter fail in its power of compensation and undergo degenerative changes. The limita- tions, aside from those set by the age of the muscle and its inher- ent power of increase, depend mainly upon the amount of proper blood which the coronary vessels are able to supply. In a great measure this is determined by the original size and construc- tion of these vessels, although doubtless there is a possibility of true hypertrophy in these so as to accommodate the growing needs of the enlarging organ ; yet if the original cause of the hypertrophy were a widespread arteriosclerosis the coronary arteries would be extremely likely to have been involved. Even were this not true, the mechanical influence of a hypertrophied left ventricle upon the walls of these vessels in close functional and topograph- ical relation with the pumping action, and the similar influences Cardiac failure. 109 of tlie aortic recoil after closure of the aortic valve, must favor the development of a local coronary sclerosis on account of the possibility of fibrillary injuries to the walls. Given an arterio- sclerosis there is every reason to expect an imperfection of the cor- onary circulation from the narrowin"; of the lumen and the in- creased rigidity of the tubes ; and with the imperfection of circu- lation thus fixed upon the myocardium, its nutrition and ability to further enlarge are necessarily limited. The functional de- mands progressing, fatigue, degeneration and cardiac failure are the necessities of a not distant future.] Diminution of cardiac force is spoken of as cardiac failure, cardiac iiisutficioicy. It follows various influences afl'ecting the myocardium or its ganglia, among wdiich as prominent examples mav be mentioned excessive exertion or fatigue, numerous poisons and the analogous substances present in the system in the infectious diseases, diminution in the blood supply to the myocardium, in- flammations and degenerations of the. muscle, excessive fatty de- posits of the heart, and atroi-)hy of the myocardium. All patholog- ical changes which occasion cardiac insufiiciency are followed by disturbances in the movement and distribution of the blood. A fatigued and weakened heart is incapable of normal contraction, expels from its chambers a smaller amount of blood than normally ; in consequence the arteries are not properly filled, the blood press- ure sinks in them and the movement of the current is slowed. The aspirating power of a weak heart is also low and the blood moves less freely from the venous side of the circulation, the veins becom- ing engorged and the pressure raised. The results of these irregu- larities differ somewhat as the left or right heart alone or the whole organ is especially involved ; in one case the lesser circula- tion, in the other the greater being the more disturbed. Many variations, too, are occasioned by the grade of cardiac insufficiency and by the nature of the original causes (cf. ancvmia and hypcr- (DJua). The luyocardium being weak the cardiac cavities do not contract as in normal conditions, contain an excess of blood, and this engorgement gives occasion for dilatation of one or both sides of the organ. Left ventricular insufficiency determines imperfect filling of the aorta and its branches, and in consequence deficiency in the amount of arterial' blood going to the brain, skin, glands and elsewhere. The heart, however, remains full and the blood is dammed back into the pulmonary veins, and the right heart experiences marked difficulty in forcing the blood through the lungs. Insufficience of the right heart, on the contrary, causes incqm;^ no Disturbances of Circulation. plete filling of the pulmonary artery, pulmonary anaemia, and, of course, the left heart in its turn receives unduly low amounts of blood. In the right auricle and larger veins engorgement ?.nd tension become marked, tending to cause a passive engorgement of the venous system throughout the body, a cyanotic liver, cyanotic spleen, etc. A heart reduced in its propulsive power is itself but poorly supplied with blood because its own arteries are but incompletely supplied. Any condition of fatigue which prevails may there- fore easily become c.vhaiistion, complete functional inability, arrest of cardiac action ( cardiac paralysis, cardiac syncope, cardiac col- lapse). All these terminal changes interfering with circulatory integrity are occasioned by any influences which impair the con- tractile efficiency of the myocardium, any agencies which either directly or indirectly reduce its muscular power (rupture, fatty degeneration, inflammation, prevention of expansion of the heart from some external interference, anaemia) ; in the same way the action of some paralyzant toxine upon the cardiac ganglia, the analogous action of thermic and electric agencies, excessive reflex stimulation of the vagus or of the vagus nucleus in the medulla oblongata (the latter from deficiency of the blood oxygen, increased blood pressure in the brain, or toxines). Just as in cases of diseases of the heart, affections of the arteries and veins are apt to occasion irregularity of distribution and movement of the blood in given organs and areas of the body. Narrow'ing of the arteries from vasoconstriction (arterial spasm), thrombus formation, inflammation and permanent shrink- age raise the intracardiac blood pressure and occasion dilata- tion and hypertrophy ; the organ to which such a constricted artery is distributed is imperfectly supplied wath blood and a variety of changes may in consequence occur in it (cf. ancrniia and embolism). Decrease in the elasticity of the vascular walls or paralysis of the arterial musculature permits the vessels to dilate, the current to become slowed and the organ, congested. Reduction in the muscular jionus of the vessels of the splanchnic area from vasomotor paralysis, usually from toxic and infectious influences, causes a massive congestion of the abdominal vessels ; in consecjuence of which the general- blood pressure falls, cardiac labor from the small amount of blood coming to the organ ensues, and there is a fatal collapse (Krehl). In the veins interference with the progression is occasioned not only by cardiac weakness, cardiac lesions and pulmonary Hypcrcctuia ami Anccmia. iii affections which interfere with the aspiration factor of venous cir- culation and h\- thromhosis of the veins ; but it should also be kept in mind that any abnormal compression of these thin-walled veins must interfere with the return flow of blood. The nearer the heart such compression occurs the greater the harm to the gen- eral body. Compression of the two venae cavre, which from the compressibility of these vessels is quite possible from pleural effu- sions, induce a reduction in the amount of blood entering the cardiac chambers and venous congestion throughout the economy (cf. hyperconiia). The lymph supply and drainage are in close relation with the abnormalities of the blood vascular system and blood circulation ; imperfections in the lymphatic circulation give rise to abnormal accumulations of fluid in the lymph vessels and serous cavities and occasion a wide group of organic lesions. Local Variations in Amount of Blood. Hyperaemia and Anaemia. The amount of blood in the organs of even healthy individuals is always subject to change and variation. The vessels are elastic tubes which are expanded by greater internal blood pressure and adjust themselves as their contents diminish. This is not merely a passive accommodation, however ; they are capable of active contraction and dilatation through the power of the smooth muscle in their structure, such alterations of lumen being primarily under control of nervous influences. The total quantity of blood in the body, similarly subject to continual variation, is never so great as to completely fill all the vessels were they fully dilated ; there exists, however, a moderate fullness, varying here and there in the organs as the blood-current meets resistance to its progression or as the blood is drawn into special organs from dilatation of this or that vascular area. The quantity of blood in the organs, and the hsemic distribution in the body generally, physiologically accommodates itself to the existing demands. More blood enters an organ when functionating; the amount traversing it dimin- ishes during periods of rest. The nervous stimulus which causes an organ to actively functionate, at the same induces dila- tation of its vessels, and in consequence a rich supply of blood is afforded. This is especially recognized in muscle. Ranke determined the blood content of the general musculature of rab- bits at rest to be 36.6 per cent, of the total muscle bulk, and noted this proportion nearly doubled (66 per cent.) when the muscles 112 Disturbances of Ci)'Ciilatio)i. were thrown into tetanic contraction. (Internal organs like the brain or intestine may tlms be relieved of excess of blood by muscular movements.) When the stomach and intestine are filled with food during digestion they are much richer in blood than when empty. The influences which give rise to this stimulation are variable and multiple, acting sometimes directly upon the muscular coats of the blood vessel wall and the nervous apparatus inherent in the wall, sometimes upon the vascular centre in the medulla oblongata (mechanical, thermic, electric, chemical irri- tants). It is but a stc]) from the physiological to the pathological, and there is no sharp line of differentiation ; change in the amount of blood in a part becomes a pathological condition when it occurs in an improper place, . or at a wrong time, or if it exceeds the normal variations. Increase in the quantity of blood in a part of the system, local engorgement, hypcrcoiiia, may be of one or other of two types, the result either of an excessive influx of blood to the part, or of a diminished escape of blood from the part. The first form, the basic feature of which consists of excessive entrance of arterial blood into the tissues, is spoken of as active hyperaemia, or, synonymously, as irrifafion-hyperccmia, congestive hypcrccmia^ fluxion of blood or arterial hypcrcvnua. Increased supplv of arterial blood may be caused by excessive blood pressure. This is met where an artery is occluded or some part of the body is for some reason prevented from receiving its proper supply : under which circumstances the blood propelled from the heart passes into the adjacent structures {collateral hypcrccmia), that is it rushes into the pervious branches of the artery near the obstruction, under the influence of the higher pressure. As a rule, however, instead of the blood being forced into the part in question, there is a lowering of the vascular tension, spoken of as a relaxation in the arterial distribution (relaxation-hyperccmia), with a resultant widening of the channels. The blood freely pours into the dilated arterial branches and capillaries, and with increased force ; in a w^ord it is drawn into the part. The degree of relaxation depends largely upon the lack of tone of the smooth muscle of the vascular wall and the congestion is therefore in such instance a myoparalytic one. Every muscle being inseparable from its innervation, nervous influences must finally be regarded as responsible for changes in the vascular tension (tone). It is assumed that the vascular Active Hypcrmnia. 113 nervous apparatus comprises two types of nerve fibres, vasodilator and vasoconstrictor ; theoretically, therefore, stimulation of the vasodilator nerves should occasion a widening of the blood chan- nels (neurotonic congestion), and the same result should follow paralysis of the vasoconstrictors (neuroparalytic congestion) , both of these influences similarly reducing the tension of the muscular elements of the arterial wall. This relation with nervous influ- ences is well seen in the fact that after section of the cervical sympathetic in rabbits the ear on the corresponding side becomes hypergemic (CI. Bernard), and after section of the splanchnics the vessels of all the abdominal viscera become distended and engorged with blood (paralysis of the vasoconstrictors). Stimulation of the nervi erigentes of the human penis causes a dilatation of the arteries of the organ ; blushing in man is brought about by psychic influences upon the dilator centre through reflex action ; certain poisons, as nicotine and alcohol, are apparently stimulating to the dilator centre. Generally the stinmlation or paralysis of the vascular nervous apparatus indicated is the direct result of local influence by physical or chemical agents. Thus hypergemia may be induced mechanically by the removal of pressure acting upon the vessels ; just as a sponge which has been squeezed and is then released takes up water, so the blood flows in large amount, imme- diatelv after removal of the pressure, into a tissue which has been deprived of its blood for a long time because of compression. The vessels here do not at once regain their contractility, but are relaxed. Similarly friction and scratching can induce hyperemia mechanically, from the nervous stimulation thus originated. Thermic influences of both types give rise to hypcnemia ; heat by its direct relaxing influence upon the vessel walls, cold first causing a vasoconstriction which later gives place to a paralyysis of the vascular musculature. There is a special group of chemical irritants as oil of mustard, cantharides, ammonia, alcohol, chloro- form, ether, saline solutions, which, either by stimulating or paralyzing the nerves of the vessel walls, cause a more or less intense arterial hyperaemia ; these, because of the value of the hyper?emia in the treatment of various affections, are of therapeutic importance (rubefacients, drugs which cause reddening of the skin). Probably in the erythemata which occur in various infec- tious diseases there also exists a similar toxic stimulation or paralysis of the vessel walls either from the bacteria or the microbic products. 114 Disturbances of Circulation. Active hypersemia is essentially an arterial and capillary dilata- tion. The hyperaemic organ or tissue therefore manifests as one of its features a red color, which is the more striking the paler the tissue normally is, as in mucous and serous membranes, and may be so pronounced that the distended arteries appear as fine deep- red lines (branched or injection erythema). The rapidity of the flow of the blood into and through the involved area, with but little output of its oxygen, causes it to remain bright red and pass thus into the veins. In peripheral parts of relatively lower temperature previous to the increased blood supply, there is a rise of temperature up to that of the blood. These peripheral parts, particularly the skin, because of their greater heat loss and their comparatively poor blood supply are lower in temperature than the internal organs ; but with the access of more blood of the body temperature the skin with its rate of heat dissipation unchanged necessarily becomes warmer. The temperature attained does not, however, exceed that of the internal organs ; and these, should they become hyperaemic, do not suffer any increase of temperature. \\'here there is marked capillary distension, provided the tissues are not rigid, there ma}- also be induced some swelling. The results of arterial hyperemia vary with its duration and location. Hyperaemia of the brain is followed by unimportant or marked disturbances of consciousness, dizziness and general excita- tion (pressure of the engorged vessels on the nervous elements). Hyperaemia of the sympathetic nerve does not cause either lachry- mation or salivation, and it is doubtful whether an uncomplicated hyperaemia causes any special lymph formation. In case of long continuance of the hyperaemia there becomes apparent an increased tissue proliferation ; this is probably not due to the increased blood supply alone, the irritant which underlies the condition having also in all likelihood some stimulative influence in its causation. As a rule uncomplicated hyperaemia is a transitory condition ; with the disappearance of the cause for the vascular relaxation the contractility of the arteries returns. Otherwise the hyperaemia may be regarded as the precursor and concomitant of inflammation. Where large amounts of blood are drawn into extensive areas of hyperaemia, a deficiency of blood (collateral anaemia) may be occa- sioned in other regions. Where the excess of blood exists in a part because of difficulty in its exit from the part it is known as passive hyperaemia or venous engorgement. This condition is encountered in connection Passive Hypermnia. 115 with low arterial pressure, the blood not being properly propelled through the capillaries, in connection with deficiency in the pro- pelling power of the heart and arteries or complete loss of the arterial reactions (atonic hypcmmia). When the blood is not kept moving onward, in compliance with the law of gravitation it set- tles into the dependent parts of the body. As the animal lies on one side the lowest parts become the seat of special engorgement (one half the lungs in the cadaver). This hypostatic or gravita- tion hypercsmia (hypostasis) takes place because of the longer persistence of the blood in fluid condition in the capillaries as compared with the larger vessels. It may be noted in animals unable to raise themselves from the ground in long protracted diseases or in the agonal period, and may also develop after death. It may, however, develop in a nondependent organ because of reduction in its arterial supply, particularly if the blood pressure in the venous trunk be so great that the blood presses back from the veins into the capillaries no longer filled from the arterial side. Since the progression of the blood in the veins depends in part upon general muscular movements and the passage of blood from the venae cavse is particularly favored by the inspira- torv expansion of the thorax, deficiency in body movements and in respiratory activity (pulmonary diseases), as may be expected, promote the development of hypostatic congestion. The most common obstacle to the venous circulation arises from compression of the delicate walls of the veins by external pressure, kinking as in intestinal volvulus, constriction or pressure from tumors; reduc- tion of the venous lumen or actual obstruction from thrombosis should also be mentioned in the same connection. Passive congestion of the portal vein and its branches, afifecting the spleen, stomach and intestines [and pancreas] is occa- sioned by all diseases of the liver accompanied by shrinkage or reduction of the capillary network of the organ, the condition interfering with the progression of the portal blood through the liver. Widespread passive hyperaemia is met in case of cardiac valvu- lar lesions because of the interferences oflr'ered to the ready move- ment of the blood from the venge cavse and pulmonary veins. A passive congestion caused by local interferences may have no further results provided the venous trunk in question or its tributary capillaries communicate by collateral circulation with other veins which are not affected, the blood then passing freel}- through such ii6 Disturbances of Circulation. collateral anastomoses. This readily occurs if such paths are at all numerous and large; and where they are of narrow calibre they are gradually widened by the pressure of the obstructed blood, so that even very small branches and capillaries come to assume con- siderable dimensions permitting the blood to escape from the area of obstruction practically unhampered (anastomotic compensation). The possibility of such dilatation depends, however, upon the degree and rate of development of the venous obstruction and requires time. In the case of sudden venous obstruction and the existence of few anastomotic channels, before the collateral branches can adapt themselves to the congestion the disturbance of the circula- tion may well induce important functional and vital changes in the affected organs ; and, of course, such occurrences are to be ex- pected if the obstructed veins have no communication with other unobstructed channels (portal vein, the veins of the kidneys and lungs). Even compression under the finger (in phlebotomy or in a rabbit's ear) will show how the impeded blood causes the veins to dilate and swell up ; all the rest of the phenomena of this form of hypersemia may be followed up experimentally in the exposed tongue of a frog or under the microscope, after the ligation of the larger venous trunks so that the blood can pass out only through the venules. The web of the frog's foot may be employed for the same purpose after ligation of the femoral vein. At first the blood in the engorged and expanding veins and capillaries becomes slowed, then irregular, now flowing forward, now back- ward, and sometimes stagnates totally. It can be seen that in some places the current is reversed, that the blood is passing out of the engorged area through the collateral branches, these gradually dilating, and the stationary or slowly moving corpuscles gradually being drawn into the current and after a time the proper rate of circulation again assumed. If a number of veins are occluded or cut off sufficient to entirely or largely prevent collateral compensation, stagnation or stasis of the blood takes place. In the affected parts of the vessel the red blood corpuscles are packed so closely together that their outlines can scarcely be distinguished and the blood completely fills the vessel as a uniform red mass. Stasis becomes especially well marked if, while the venous outlets are completely closed, the blood continues to be forced in from the arteries. The capillaries dilate to their fullest : their walls, permeable to the plasma even before their distention, can no longer hold the fluid blood, but allow Passive HypercEmia. 117 it to escape more or less freely according to the pressure, and may in fact, rupture. However, even if the blood be not forced into the area from the arteries, exudation of the fluid part of the blood through the distended capillary walls may take place in ordinary atonic hypostatic congestion, and there may even occur a diapcdesis of red blood cells. The endothelium and vessel walls remain intact only while they are being continually bathed with moving blood ; and as soon as the circulation stops it may be accepted that a disturb- ance of the endothelial nutrition exists, these cells then shrinking and causing comparatively large open interstices, through which exudation takes place. For these reasons passive hyperemia has frequently associated \/ith it a congestion-transudation and haemor- rhage. The latter may be sufficiently severe to make the whole tissue dark red in color, infiltrated and completely occupied by blood (haemorrhagic stasis, h?emorrhagic infarction). The pressure occasioned by the distended vessels and the fluid exudate, together with the impediment to circulation, may be fol- lowed by cessation of function of the aft'ected tissues and finally by their death. The longer the blood remains in the capillaries, slowly giving oft' its oxygen and capable of but little or no renewal, the darker it becomes ; the tissues in venous hyperemia arf there- fore of a dark bluish red (cyanotic) hue. Such a tir.t (diffuse cyanosis, black erythema) may be encountered (in hogs) extending over practically the whole surface of the body in case of general passive hyperaemia. The lack of oxygen and the excess of carbon dioxide in the venous blood are partly responsible for the functional disturbances arising from passive hypersemia of the various organs ; these conditions act by stimulating the medulla, and occasion dyspnoea, dizziness, convulsions, disturbances of consciousness, muscular weakness and fatigue. The superficial external parts of the body, when passively con- gested, become cool because of the impeded circulation of blood through them, because the blood is cooler than normal and the heat dissipation not diminished. In contrast to wdiat has been said above, a mild but persistent passive hypersemia is apt to cause not only a swelling of the organ affected (kidneys, lungs, liver, spleen) because of the permanent engorgement and distention of the capillaries, but in addition may induce an increase in size and induration from the production of an excess of connective tissue in the part (Cf. hypertrophy). ii8 Disturbances of Circulation. Stasis and stagnation of the blood may at times be caused by substances which act by inducing a withdrawal of the fluid elements and thus a thickening of the blood (chemicals acting upon vessel walls). [This can well be shown experimentally by bathing the mesentery of a frog, arranged for demonstrating the blood current, with a hypertonic saline solution, a rapid exosmosis of fluid taking place and the current being soon entirely checked, with the vessels choked with corpuscles.] Deficiency of blood in an organ may be part of anaemia of the general body (general oligsemia or an?emia ; d priv., 6\lyos, little, and al/xa, blood) or a consequence of local impediment to the blood current (local anaemia, ischaemia, from taxeiv, to limit or check). The blood supply to any part mdy be impeded by: 1. Pressure upon the part (coniprcssion aiuvniia) from in- crease in. the bulk of adjacent organs, accumulations of fluid or any other compressing influence upon the part from without, or by nar- rowing of the capillaries by fat deposit, fluid or air in the paren- chyma of the organ. 2. Narrowing, occlusion or fault of contractility of the arteries. Here may be mentioned external pressure upon the vessel, ligation, occlusion by solid bodies as by thrombi in the arterial lumen (cf. thrombosis and embolism) , rigidity of the vascular walls from cal- cification or sclerosis and spasm of the arterial musculature with resultant contraction of the lumen {arterial ancemia or ischccmia, occlusion ancrmia, spastic ancemia). 3. In addition, anaemia may involve a certain part of the body in case the general blood distribution is irregular because the gen- eral volume of blood passes to one large area to the deprivation of other parts (collateral ancrmia); as when the posterior parts of the body are markedly infiltrated with blood (symptomatic anthrax) the fore parts are rendered ansemic, or as when interna! haemorrhages occur the flesh is left ansemic, etc. The organ or tissue deprived of its blood looks pale, the absence of the blood tint permitting the peculiar hue to become more appar- ent and more like the tissues of slaughtered animals or like a washed tissue deprived of its blood by the washing. It contains less fluid and but little blood appears on the sectioned surface, and its volume is diminished because of the emptiness and collapse of the vessels. Ansemic parts at the exterior of the body, being exposed to the air and losing their heat, feel cool, because with the loss of blood their principal thermal substance is lost and they are capable of producing little or no heat in themselves under the circumstances ; Local Aiuviiiia: IJa-uiorrha^e. II9 and with the existing diminution of nutritive and secretory sub- stances disturbances of nutrition and diminution of functional aoility must ensue. In addition the products of previous meta- bolic activity necessarily remain in the anaemic tissue and may act unfavorably upon it. According to the grade of oxygen depriva- tion, need for nutrition and rapidity of metabolism in the affected structure there must sooner or later result a gradual death of the anaemic part, because of the absence of blood. It should be kept in mind, too, that the integrity of the endothelial lining of the blood vessels depends upon the continuous flow of blood through the vessel and that these cells gradually degenerate and become permeable when the anaemia is complete. Should the blood again flow through such capillaries which have been empty for perhaps twenty-four hours it readily escapes through their walls, with con- sequent haemorrhagic infiltration of the surrounding tissues. (After interruption for as much as two hours the renal epithelial cells become necrotic and consequently the renal function becomes checked or ceases entirely.) Suspension of activity in vital organs because of anaemia is a matter of extreme gravity. Cerebral anaemia is quickly followed by unconsciousness ; and because of degeneration of the central nervous tissue, even after but brief periods of anaemia, this condition in the brain and spinal cord is likely to give rise to destruction of the ganglion cells and focal lesions with symptoms of paralysis. Complete anaemia of the myo- cardium necessarily causes cessation of the heart's action. Other parts of the system, as the skin and muscles, are less sen- sitive to the effects of anaemia ; their tissue may withstand the condition for some hours, as may readily be appreciated by the practice of artificially causing an anaemia in surgical operations by means of the Esmarch's elastic bandages. In case of such resistant parts, if the cause of the anaemia be eliminated the results may be but transient or only partial, as in case of the anaemia of cramps (spastic anaemia) or anaemia caused by external pressure. Ob- struction of an artery, and more particularly the anaemia resulting therefrom, may be corrected if the blood supply can be quickly re- established through the anastomotic vessels (so-called collateral paths). Loss of Blood; Haemorrhage. The escape of blood from the vessels into the tissue spaces, bodv cavities or to the free surfaces of the bodv is known as I20 Disturbances of Circulation. bleeding, haemorrhage {al^a, blood: ^^705, rupture) or extravasation { extra, without ; 'vas, vessel). The most common causes of haemorrhage are wounds and lacerations of the vessel walls. Anything which severs the con- tinuity of the vascular wall by puncture, incision, tearing, con- cussion or contusion affords opportunity for the effusion of blood (traumatic liccniorrJiage). In the same way all conditions which impair the resistive strength of the vessel walls to the pressure of the blood favor haemorrhage, as the lesions caused by the action of corrosive fluids, fatty degeneration of the walls of the vessels, vascular inflammations leading to brittleness and fragility of their tissues (corrosion hcruiorrJiage, spontaneous hcemorrhage). Exaggeration of blood pressure (increase of pressure from sud- den and powerful cardiac contraction and from hyperVemia) per- mits the rupture of these weakened vessels, or perhaps even nor- mal pressure may be sufficient. Rupture of the liver is not infre- quently met with from such a cause after fatty degeneration of its vessels and tissues. Or when the muscle of an artery (after chronic inflammation) is in a degenerate state its walls may be distended to form permanent dilatations [aneurisms] ; here the wall comes to consist of but little more than connective tissue, which tears when the distension becomes great. Haemorrhages of the types mentioned are spoken of as haem- orrhages per rhexin ( prj^is, rupture; prjyvwai, to burst through), or, ])articularly where the wall has been weakened by pathological changes, as haemorrhages per diabrosin ( bia-^i^pdocrKiLv , to eat through ) . The blood maw however, leak out of the smaller vessels, capillaries and veins, without the apparent existence of any lesion in the continuity of structure, because of some abnormal pemie- ability of their walls. Such haemorrhage is known under the names diapedesi::, or luemorrhage per diapedesin ( from Sia-v-ndav, to burst through). The increased permeability of the vessel wall is explained by the fact that under the influence of toxic, infec- tious, thermic or other injurious agencies, as well as from marked engorgement and distension of the capillaries (passive hyperaemia, stasis), the cement substance between the endothelial cells becomes porous ; for example, the endothelial cells may shrink into globular form and separate from each other, or openings may result from destruction of the cells. The red corpuscles then slip through between the cells or are forced out along with the plas- Hemorrhage. 121 inatic exudate ; because of their elasticity these corpuscles are easily able to pass through the most minute clefts of the cement substance. There exist therefore in these cases minute micro- scopic tears. Haemorrhage by diapedesis, however, may assume important proportion and may be fatal because of its location (as in the brain or stomach) or of its duration. Since it is the bathing of the endothelium with nonnal blood which is essential to its integrity, it may be easily appre- hended that even a temporar\- interruption of the circulation to FU 1. Mesentery of the dog. (a) IliPmoirhago by diapedesis. (b) Ecchymosis occurring in a similar manner, tlie opening in the wall of the cajiillary having closed up again. The figure aU-o t-.hows an emigration of leucocytes. Magnified 2.50 times. I After Thoma. ) the capillaries may render them abnormally permeable and be the cause of diapedesis after restoration of the flow (cf. oiibolisDi). Haemorrhages are also classed according to the type of vessel from which the blood escapes, as arterial, z'enous and capillary hcemorrhagcs ; where the blood oozes from a widely diffused fault in the softer tissues, as in the liver, and the type of the bleeding vessel cannot be made out, the term parenchymatous hcemorrhage is appropriate. The blood may escape freely to the exterior of the body or 122 Disturbances of Circulation. into one of the internal body cavities (external and internal hcemor- rliage, surface hcumorrhage and hccmorrhage into a cavity). When the exuded blood fills the tissue spaces and completely saturates the tissvies, the terms ]ia:niorrhagic infiltration or hccniorrhagic in- ^ farction {infarcere, to stop up or fill up) are applied, the latter term being used particularly when the blood coagulates in the tissue and remains in it as a dense compact mass [usually in a definite circumscribed area of infiltration further described in connection with embolism]. If the bloody effusion causes an extensive, loose, gelatinous swelling of the tissue, diffusely filling the structure [applied particularly to infiltration beneath some sur- face], it is spoken of as a suffusioii {suffundcre, to pour) or snggillation. Small circumscribed foci of haemorrhage, apparent as spots and points from which the blood cannot be discharged by pressure (especially in serous membranes), are called hccmor- rhagicc niacnlosce, eccJiyinoscs [xv/Modv.to overflow), petechice (from pidoccliio, louse or its bite; or from pediculce flea-bites [petigo, eruption]), or vihiccs when in streaks {zibc.v^ a streak). When the extravasated blood collects in a rounded mass, as when it dissects u[) the capsule of an organ or a connective tissue structure, or when it accumulates in a cavity or becomes encapsulated by a surrounding inflannnatory zone, the mass is spoken of as a hccniatonia (blood boil) or hccniorrhagic cyst. Special terms are also employed for these effusions of blood depending upon their location : an extravasation of blood into the pleural cavity is termed hccmothorax ; into the peritoneal sac, hcemoccclia ( koiXIo., the body cavity) ; into the pericardial cavity, ha:mopericardium ; into the uterus, hcematometra (fj.r}Tpa, uterus) ; into the sac of the tunica vaginalis testis, hccniatocele (/ctjXt?, rupture). In addition special names have always been made use of in con- nection with haemorrhage from special organs : epistaxis ( iin-aTA^iiv, to drip) for nasal haemorrhage; liccniaturia (o^pov, urine) for the escape of blood with the urine ; hcrniafcniesis ( efieiv, to vomit) for gastric haemorrhage (also melcrna, fieXaiva vocros, from /xAas, black, because of the dark brown color given the blood by the gastric juice) ; haemoptysis {ittvuv, to spit) for expectoration of blood from the lungs ; metrorrhagia for haemorrhage from the uterus ; hccnwrrliagic apoplexy {dirowXiffanv, to strike down, to stun) for Spontaneous haemorrhage of the brain. Symptoms and Results. From its characteristic blood tint an eft'usion of blood is easily recognizable anatomically as a dark red accumulation of blood, or spot which cannot be effaced and which Hemorrhage. 123 is more or less sharply circumscribed. Upon surfaces or in the body cavities the extravasation presents a striking picture, in profuse, partly coagulated, partly fluid masses, or in a gelatinous, red, jelly-like tumor ex- tending into the loose sub- cutaneous or sub-mucous tissue (haeniorrhage fol- lowing contusions of the abdominal walls, hremor- rhagic stasis of the in- testinal m u c o u s mem- brane), or sharply outlined in numerous definite drop- h like flecks (not effaced on % pressure) as seen in the ^ sub-serous cellular tissue of the pleura, pericardium and epicardium. In the secretions it is easily ap- preciated by the more or less pronovmced blood tint which it imparts to them ; the intestinal contents may assume a slightly reddish - gray, cafe-au-lait color up to a chocolate brown or pure blood-red from the admixture of blood ; the gastric contents a sepia- brown, the urine a blood- red to black; the expecto- rate and nasal secretion a rusty, red-streaked or foam y red appearance (pulmonary oedema). While it is usually easy to detect the ruptured ves- sel in case of massive haemorrhages (as a ruptured aneurism, the eroded stump of a ves- sel in hemorrhage from gastric ulcers), and the infiltration of blood surrounding the lesion in the organ points to the origin of the haemorrhage and indicates its intravital occurrence, Fig. 2. Ilaematoma of the spleen of horse. 124 Disturbances of Circulation. yet in capillary diapedesis from a mucous membrane, as the gastric or intestinal lining, the points of escape are invisible to the naked eye, and only the blood deposit on the surface and the pallor of the mucous membrane indicate the fact of extravasation. Arterial haemorrhages are recognized in living animals by the bright red color of the arterial blood, by the spurting character of the escaping stream from the larger arteries, the spurts corresponding to the cardiac contractions ; while the bleeding from the veins is con- tinuous and without pulsation. However, an arterial spurting may be prevented by the interposed parenchyma (Samuel). If the larger vessels between the point of haemorrhage and the heart be com- pressed the haemorrhage will diminish if it be arterial ; it will be increased if venous. The results of hcoiwrrJiage depend upon the quantity and the duration of the bleeding, as well as the location of the lesion. In case of loss of over one-third of the total volume of blood (about 3 to 4 per cent, of the body w^eight ; the average total quantity being from one-tenth to one-twentieth of the weight of the body), the flow continuing, the blood pressure falls. The vessel walls, although capable of wide adaptation to the volume of blood within, have become too wide for the diminished amount and cannot longer advantageously propel it. A general oligaemia has been established, indicated by the pallor of the mucous membranes, dizziness, faint- ing (^an^mia of the brain) and convulsions, and the animal may bleed to death. These results occur not only when the haemorrhage is external, but also in copious haemorrhages into the intestinal lumen, peritoneal cavity, etc. (internal haemorrhage). Haemorrhage gradually ceases by the closure of the opening in the vessel from the formation of a blood coagulum in the opening (adhesion thrombus), the closure being facilitated by constriction of the vascular lumen (contraction of the wall), external pressure (by the tissue engorged with blood), and by the fall of blood pressure. After such cessation the volume of the fluid portion of the blood is soon restored. The watery element first passes into the vessels from the tissues and for a time the blood is conse- quently more fluid (hydraemic) than before the haemorrhage; but gradually the blood cells, regain their normal numbers as their regeneration (cf. chapter on regeneration) proceeds in the blood forming organs. At the site of haemorrhagic infiltrations the tissues present more or less functional alteration. The presence of the extravasated Hcem rrhage. 125 mass of blood exerts a certain amount of pressure and in conse- quence the cells and tissues are forced apart, displaced by the in- vading blood ; and hollow viscera are occluded by the coagulated blood. Even small haemorrhages in the brain, according to their precise location, occasion a loss of function in the area affected, perhaps even to the extent of complete obliteration of conscious- ness ; in the case of spinal haemorrhages palsies ensue : hccmorrhage under the mucous lining of the air passages (fracture of the trachea and larynx) forces the same into the lumen to such a degree that the air passage is constricted and death from asphyxia may result. The escaped blood usuall}^ coagulates, precisely as the blood in venesection (cf. chapter on thrombosis). Should this clot remain in the tissue or in one of the serous sacs it acts as an inflammatory excitant ; it attracts the leucocytes by chemotaxis and causes a limiting zone of connective tissue proliferation about it. This gradually forms a capsule about the collection of blood, transform- ing it into a haemorrhagic cyst, often called a haematoma, in which the disintegrating blood exists, partly as soft, elastic, fibrinous masses, of a reddish or brownish color, partly as liquid serum ex- pressed from the clot. Such h.Tmatomata, sometimes approaching the size of a human head, are not infrequently seen in the spleen of domestic animals, around the kidneys in swine, and in the pelvic cavity of cattle as the results of contusion haemorrhages. On the other hand the penetration of leucocytes to the mass and the pro- liferation of fibroplastic and angioplastic tissue leads to the resorp- tion of the blood. Its disintegrating elements are taken up by the amoeboid cells and carried away ; the plasma is absorbed by the cells and may pass off through the lymph paths. The red corpuscles both in the tissue lymph and in the blood vessels begin to swell and lose their color or to become shriveled. The coloring matter, haemoglobin, having been dissolved out may soak through the tissue dift"usely or may become deposited in the form of flakes, granules or more rarely as crystals through the tissue. The crystalline form is especially apt to occur where the blood has been stagnant (haematoma), appearing as ruby-red to brown, minute rhombic plates and needles (iron-free haematoidin) ; the granules are yellow and angular, sometimes give an iron reaction (haemosi- derin), sometimes undergo a change like the crystals b\' which the iron is separated from the haemoglobin, iron-free haematoidin (haemofuscin) remaining. 126 Disturbances of Circulation. This blood precipitate is found microscopically not only at the site of haemorrhage, especially in the amoeboid cells which are loaded with it, but also in the nearest lymph glands which are often found tinted all through by a rusty, reddish-brown color from the quantity of blood pigment conveyed to them. In the dead body, on account of sulphur products (sulphuretted hydrogen) of the cadaveric bacteria, the site of a haemorrhagic infiltration may be found changed to a slate gray to black hue by the sulphur com- binations ; in life, too, in places where similar bacterial accumula- tions and fermentations occur (intestine, abscess cavities, fistulous paths, mycotic diseases of the bladder) the pigment may undergo the same changes in color and thereafter remain as evidence of previous haemorrhage. Dropsy. Hydrops and Oedema. Excessive accumulation of the tissue fluid or lymph in the lymph spaces, lymph vessels and serous sacs (Ivmph sacs) is spoken of as dropsy, hydrops (from vSa>p, water) or hydropsia, and. if the accumulation has occasioned swelling of the tissue, as oedema (from or5a;'. to swell). The process itself is described as a dropsical transudation (from sudarc, to sweat) ; the accumulated fluid as a transudate. Neither the process nor the transuded fluid is essentially anything more than a quantitative disturbance of physiological lymph-production. Lymph is originally derived from the blood, and is regarded by many as a secretory product of the endothelium of the capillaries, although the blood pressure is also maintained as a factor in its production and accumulation, affecting the filtration of the liquid part of the blood through the capillary walls. [Whether the physical processes of dialysis and osmosis should also be invoked here is debated. Lazarus-Barlow, in dis- cussing the vital transudation of lymph, urges the importance of tissue demands for lymph both for purposes of nutrition and for its influence in diluting and removing various products of their metabolic activities or of their degeneration, and points out that in this last case there exists a possible explanation for the per- sistence of an oedematous process in case the excretory organs as the kidneys fail of eliminating from the blood the various waste materials. Thus if, in a case of nephritis, the blood becomes sur- charged with waste materials and if at the same time such waste in a local area of special activity or of degeneration is excessive, Dropsy. 127 the tissue demands for increased transudation are increased in order to acconiplisli its removal by the lymph ; yet if the blood already contain an excess of the very substance in question the increased transudation only serves to more nearly complete a vicious cycle, and adds to the existing accumulation.] Two reasons may be assumed for the pathological increase of this fluid in the tissues, either an obstruction to the lymph drainage, or an unusual, exaggerated transudation ; both of which factors may be operative at the same time. In_ view of the free anasto- mosis and the great abundance of lymph channels, together with the fact that lymph absorption is also accomplished by the capil- laries and veins, obstruction of isolated lymph channels, it may be said, does not ordinarily occasion lymph stasis. Even in case of unusual formation of lymph there is no essential reason for determination of any abnormal condition, as within certain limits the paths of lymphatic drainage are capable of accommodating and carrying ofl:" large quantities of fluid, provided the tissues retain their ]iroper elasticity (Landerer), and the propulsive forces (muscular movements, etc.) are of normal functional ex- cellence. It is only when the increased transudation becomes ex- treme and the lymphatic flow fails to keep pace, that cedema develops. The most common cause for such fault is passive hyperemia. In case of passive congestion the blood pressure in the capillaries becomes raised and the current of blood slowed, as a result of which the endothelium of the walls of the capillaries becomes ab- normally permeable and in conseqtience the fluid element of the blood exudes profusely. This exudate is usually not as rich in albumen as the normal lymph. As examples of oedema of this type may be suggested that caused by compression (as oedema of the lips by application of twitches to a horse's mouth), by venous thrombosis, by cardiac lesions which impair the current of blood in the ven^e cavie, by pulmonary changes which prevent proper progression of blood from the right heart, by structural faults of the liver causing obstruction of the portal capillaries and producing portal congestion (dropsy or cedema from passive congestion). Coincident interference with lymphatic drainage may be determined perhaps by the pressure of fluid accumulations in the thoracic or peritoneal cavities upon the thoracic duct, per- haps by the loss of natural elasticity of the tissues, stretched and 128 Disturbances of Circulation. distended by the increased and persistent pressure of the lymph- atic transudate. Increased transudation is observed also in connection with in- flammation and changes of the vascular walls caused by toxic chemical agents acting either locally or, when circulating in the blood, widely {irritative or inflammatory dropsy). One should recall in this relation the influence of the slowing of the blood current and vascular dilatation, together with possible shrinkage and separation of the endothelial cells, combining to render the vessel walls more permeable ; moreover, a number of poisons, as some of the products of metabolism, seem to directly stimulate the endothelium to increased secretory activity, to possess what might be called a "lymph-driving" ( lymphogogue) action. In addition it may be pointed out that in inflamed tissues the lymph flow is impaired by the fact that the inflammation occasions coagulation of the lymph and impairs the elasticity of the tis- sues. Such features explain the occurrence of cedema around tissues which are the seat of purulent or hsemorrhagic inflamma- tion (collateral cedema). Dropsy is often concurrent with wasting diseases and abnormal states of the blood characterized by poverty of its cellular ele- ments and increase in its jiroportion of water, the so-called cachectic or hydremic wdenia, as seen in cases of pulmonary verminosis, fluke disease of the liver and chronic parenchymatous nephritis. It is an open question in such cases whether the es- sential fault in determining the dropsy is the dilution of the blood which may perhaps make it filter more readily through the vessel walls, or whether we should ascribe it to the presence of metabolic products and other toxic matter in the circulating blood impairing the vascular endothelium and permitting the transudation because of an increased permeability. (Cohnheim and Lichtheim failed to obtain dropsy by introducing large quan- tities of sodium chloride solution into the blood of experiment animals, even when as much as half of the blood was replaced by the saline solution ; Gartner, however, succeeded in causing an oedema in dogs by long continued infusion of salt solution.) No satisfactory explanation exists for the rather common congenital anasarca of aborted calves. According to the investi- gations of L. Franks the thoracic duct is sometimes missing in these "watei: calves" (or "Dunstkalbern") : while in other cases Dropsy. 129 renal changes, perhaps the sequels of an intrauterine nephritis, are met which may occasion dropsies because of retention of water or on account of some infectious toxic influence present. The dropsical transudate is usually a colorless or wine-yellow water-like fluid, generally containing a smaller proportion of albumen than the lymph and fluid exudates, as a rule showing only 0.1 to 0.8 per cent, albumen, according to Perls up to 5 Fig 3. Anasarca universalis congen., so-called water calf. per cent. (Lymph and blood plasma contain about 7 per cent.) The proportion of salines is the same as in the plasma (0.8 per cent). [The precise composition, particularly as relates to pro- teid, varies in the different types of dropsical fluid; and even hi the same subject the amount of proteid is not identical in fluid from different parts of the body, that from the subcutaneous tissue being usually marked by the lowest proteid content, while 130 Disturbances of CirciilatioJi. that from the serous cavities, especially the pleura, is apt to be richer in albumen.] In case of coincident escape of blood corpuscles (in passive hypersemia) admixture of these elements with the transudate may occur to a sufficient extent to give it a blood-red color and occasion fibrin deposition {^hydrops hcemor- rhagicus). In other instances admixture of fat from the blood or from, fatty degeneration of the cellular elements macerated in the fluid may give a milky appearance to it (hydrops adiposus, chyliformis) ; and in abdominal dropsy a similar appearance may be occasioned by rupture of the chylous vessels and admixture of chyle with the fluid (hydrops chylosus). The amount of fluid in the large body cavities may reach con- siderable volume, 10. 50 to 100 liters in large domestic animals. Such quantities of fluid are naturally capable of exerting marked pressure upon the dift'erent adjacent organs, and distend the walls of these cavities. Consequently in case of ascites the peritoneal cavity is considerably enlarged and becomes a fluctuating sac ; the pericardial sac attains a wide outline and fluctuates ; and even the chest wall may be distended and barrel-shaped from the separation and outward displacement of the lower ribs. In the foetus, in which the fontanelles are still yielding, the covering of the brain becomes a huge sac. partly membranous, partly made up of the cranial bones forced apart and transformed into thin plates. When the transudate fills the spaces of a tissue the porous cellular structure becomes a gelatinous, amber-colored, swollen mass, from the cut-surface of which a serous fluid drips and whose doughy swelling retains for a long time the pressure marks of a finger. Sometimes bladder-like collections or cysts may form from the forcible distension of the connective tissue spaces. Various terms have by custom been applied to these accumula- tions of transuded fluid. CEdema of the skin is spoken of as anasarca (from avi and adpi,, flesh; supply hydrops): collec- tions in the pleural cavities as hydrothorax ; in the pericardial sac, hydropericardhim; in the peritoneal cavity, ascites (from d