A system of practical medicine. By American authors. Vol. 1

by Unknown

GENERAL PATHOLOGY.

---

GENERAL MORBID PROCESSES.

GENERAL ETIOLOGY.

HYGIENE AND QUARANTINE.

DRAINAGE AND SEWERAGE IN RELATION TO THE PREVENTION OF DISEASE.

GENERAL MORBID PROCESSES.¹

INFLAMMATION; THROMBOSIS AND EMBOLISM; EFFUSIONS; DEGENERATIONS; TUBERCULOSIS; MORBID GROWTHS.
BY REGINALD H. FITZ, M.D.

¹ In the preparation of this subject full and free use has been made of the following works: Die Cellular Pathologie, Virchow, 4te Auflage, Berlin, 1871; Handbuch der Allgemeinen Pathologie, Uhle und Wagner, 7te Auflage, Leipzig, 1876; Handbuch der Allgemeinen Pathologie als Pathologische Physiologie, Samuel, Stuttgart, 1879; Vorlesungen über Allgemeine Pathologie, Cohnheim, 2te Auflage, Berlin, 1882; Lehrbuch der Pathologischen Anatomie, Birch-Hirschfeld, 2te Auflage, 1er Band, Leipzig, 1882; Lehrbuch der Allgemeinen und Speciellen Pathologischen Anatomie, Ziegler, 1er und 2er Theil, Jena, 1882 and 1883.

---

GENERAL MORBID PROCESSES.

Disease is to be regarded as representing the result of a series of processes called morbid or pathological, from the fact that they are manifested by disturbances in the organism.

The processes concerned are the same in kind as those essential to health, but they are modified in time, place, or quantity.

Morbid processes, therefore, are to be considered as modified physiological processes tending to cause disease.

All physiological processes are subject to certain variations which tend to produce disturbances in the functions of the body. In the healthy organism this tendency is checked by the automatic regulators of the functional activity of the various organs, to the importance of which Virchow² long ago called attention. By their action the influence of external agents is controlled within certain limits. The lids close and prevent injury to the eye. Sneezing, coughing, and vomiting bring about the expulsion of noxious irritants. Sweating aids in neutralizing the injurious effects of exposure to high temperatures. Rapid respiration permits a sufficient cleansing of the blood in rarefied atmospheres. When the limits, within which the regulation of physiological processes is possible, are exceeded, such processes become pathological and disease begins. A morbid process, therefore, is usually incapable of recognition till disease is present. It may exist and disease be unsuspected and denied. A diminished blood-supply may be one link in the process which eventually leads to the production of disturbances. Another link is to be found in the fatty degeneration resulting from this lack of blood.

² Handbuch der Speciellen Pathologie und Therapie, Virchow, 1er Band, p. 15, Erlangen, 1854.

Such a degeneration may have long existed in the walls of a blood-vessel, and yet the individual appear in the best of health. The sudden rupture of the weakened wall results in death or disease. With the manifestation of the disturbances which render the condition of the vessel obvious the individual is said to be diseased.

In most instances, however, the morbid process makes itself early apparent. Disturbances of nutrition, formation, or function soon become sufficient in quantity to attract attention from the resulting discomfort, and the presence of disease is then recognized. The latter is thus essentially a conventional term, and begins when the morbid processes occasion a sufficient degree of inconvenience.

The process is never at a standstill. It either tends toward a return to the physiological conditions, or its course is in the direction of their destruction. As physiological processes are absolutely dependent upon the vitality of the elements of the tissues, so those which have become pathological cease to exist with the death of such elements. In the dead body there is no disease, although its results remain, and furnish the most efficient means of identifying the processes which occasioned them.

In the study of morbid processes, therefore, one must appreciate the normal conditions and manifestations of life in the individual. Physiological laws govern pathological phenomena, and the latter must always be submitted to the tests furnished by the former.

Just as little, however, as the study of anatomy familiarizes the student with the anatomical changes resulting from diseased processes, does the study of physiology accustom the student to the features of disease. Pathological processes must be studied by themselves and for themselves, although the means which are employed may be the same as those used in physiological research.

It is evident that the exactness of method which is the demand of the physiological investigator cannot be secured by the pathologist. The material of the latter lies farther, beyond his control. Nevertheless, much of the ground to be gone over is common, and the object sought for is essentially the same—the knowledge of the conditions necessary to maintain life.

In an introduction to the study of disease there are certain processes which deserve early recognition. They are both the cause and the result of disease, and may occur in various diseases, either limited to one organ or present in a series of organs. Their treatment at present obviates the necessity of repetition, and prepares the reader for the special consideration of their occurrence in the various structures and systems of the body.

These processes are named in virtue of some prominent characteristic, and each is made up of a complex series of conditions and disturbances. In part, they represent modifications in the circulation of blood and lymph; in part, they consist of nutritive derangements, whose consequences appear as the various degenerations, or as the additions to the body, the new formations.

The processes and groups of processes in question are those included under the following heads: inflammation; thrombosis and embolism; effusions; degenerations; tuberculosis; and morbid growths.

Inflammation.

Inflammation is characterized now, as in the time of Galen, by the presence of redness, heat, swelling, and pain. The disturbance of function, added to modern definitions, is to be regarded either as a result or a cause, or both, of the variously modified physiological processes whose sum is the inflammation.

The redness of inflammation is obviously dependent upon the presence of an increased quantity of blood. This is readily apparent in the direct observation of the blood-vessels of an inflamed, transparent part of the body, as the mesentery of the frog or rabbit, or the tongue and webbed foot of the former animal. The redness of inflammation consequently demands the presence of blood-vessels in the affected region, and becomes all the greater the more vascular the part—i.e. the richer it is in such vessels.

Redness does not suffice for the existence of inflammation, for it may be found in the absence of other evidence of the latter. The diffused redness, often extensive, of birth-marks, that from venous obstruction or temporary congestions, from vaso-motor disturbances—the section of the sympathetic furnishing a well-known instance—are examples of non-inflammatory redness. Inflammation may even be present without redness, as may be constantly observed in the occurrence of parenchymatous inflammation and of the chronic interstitial varieties.

The heat of inflammation is one of the most important clinical features, yet not indispensable, as appears from its absence in chronic interstitial forms of inflammation. In the acute varieties of inflammation an elevated temperature is constant, and its observation and record furnish a most valuable means of determining the beginning and progress of an inflammation, which, for a time, may furnish but little additional evidence.

The heat of inflammation is the prominent characteristic of inflammatory fever, and it is the study of this variety of fever of late years which has resulted in an intelligible and relatively satisfactory theory concerning fevers in general. Information of much value is to be found in the recent work of Wood,³ which contains abundant historical information, as well as extensive original observations and conclusions.

³ Fever: A Study in Morbid and Normal Physiology, H. C. Wood, A.M., M.D., Philadelphia, 1880. (Reprint from the Smithsonian Contributions to Knowledge, No. 357.)

Inflammatory fevers are distinguished from idiopathic forms. The latter variety includes the occurrence of fever as an attribute of the disease concerned, the more characteristic symptoms of which follow the febrile outbreak. Local inflammatory processes may take place during the progress of the disease with its fever, but such processes are co-effects of the cause of the latter, rather than its cause. Most of those diseases in which fever occurs as one of the joint effects of the cause of the disease, are included among the infective or zymotic classes.

The inflammatory fevers are those attending an acute inflammatory process, and are secondary to, and occasioned by, the latter. The type of this variety is seen in the fever occurring during the progress of a wound, whether its course is toward healing or extension. Such traumatic fevers are characterized as septic or aseptic; the former including the conditions of septicæmia and pyæmia. The aseptic traumatic fevers, as described by Volkmann,⁴ are those which pursue their course with an elevated temperature, but without most of the other febrile phenomena.

⁴ Beiträge zur Chirurgie, Leipzig, 1875, p. 24; Sammlung Klinischer Vorträge, No. 121, Genzmer und Volkmann.

Fever in general is characterized by a combination of disturbances in the physiological processes of the body. Such processes are those concerned in the production and dissipation of heat, in respiration and circulation, digestion and secretion, and in mental, motor, and other sensorial action. Such disturbances are manifested by a persistent elevation of temperature, an increased destruction of tissue, a quickened and modified pulse, accelerated breathing, increased thirst, diminished appetite, and diminished quantity and altered quality of the secretions. The sensorial disturbances include wakefulness and stupor, headache, delirium, twitchings, cramps, and other symptoms indicative of functional impairment of the nervous system.

Of all these manifold evidences of fever, the elevation of temperature is the one whose cause, range, and results have been most carefully and critically investigated. No record of a case in which fever is present is regarded as complete without the chart of the daily variations in temperature, respiration, and circulation. The practical value of such records is thus admitted, and in the experiments relating to the origin of animal heat the observations of temperature are as essential as the chemical analyses, each of which supplements the other.

The more accurate determination of the heat produced in the body is obtained either by the use of the calorimeter (an apparatus for measuring the collected heat liberated from the body) or by estimating the quantity of heat produced in the destruction of the constituents of the body from quantitative analyses of the discharged carbonic acid and urea. The results of such investigations are regarded by Rosenthal⁵ as possessing only a relative value, but justify the conclusion that most of the heat produced in the organism results from the oxidation of its constituents.

⁵ Hermann's Handbuch der Physiologie, Leipzig, 1882, iv. 2, 375.

For the preservation of health it is essential that this heat should be removed from the body in such quantity that the temperature of the latter shall not vary to any considerable extent, for any considerable time, from 37.2° C. (98.4° F.). The removal of the heat is mainly accomplished by its radiation or conduction into a surrounding cooler medium, and by the evaporation of moisture from the surface of the body. Too great a removal of heat results in death from freezing, while too great an accumulation of heat terminates fatally from the effects of an unduly elevated temperature. To ensure the normal range of temperature, constantly changing relations must exist between the production of heat and its dissipation. The cooler the surroundings, the more must heat be produced, or the less must heat be evolved from the body.

An increased production of heat is obvious under conditions of climate demanding prolonged exposure to low temperature. An abundantly fatty diet promotes the formation of heat, while suitable clothing checks its dissipation. Although it is claimed by Liebermeister that sudden exposure to cold stimulates heat-production, Rosenthal⁶ disputes this statement, and maintains that it is still to be regarded as doubtful whether the production of heat can be varied to suit the demands of sudden and temporary changes of temperature. With the admission of this doubt, the regulation of the temperature of the body, under the circumstances just referred to, is mainly accomplished through the influence of agencies favoring or checking the loss of heat. Since heat is largely brought to the surfaces of the body by the circulating blood, modifications in the fulness and rapidity of this superficial current produce corresponding differences in the amount of heat and moisture presented. Such variations are considered to be accomplished through the action of the vaso-motor nervous system, whose differing effects are apparent in the pale, cool skin and the flushed, warm surface.

⁶ Op. cit., 413.

The search for the regulation of such vaso-motor action has led to the view that the production of heat, as well as its dissipation, may be influenced from a nervous centre. Wood⁷ claims that the result of experiments made by him proves the existence of such a heat-centre in or above the pons. Although admitting the possibility of its being a muscular vaso-motor centre, he regards it rather as an inhibitory heat-centre, which acts, as suggested by Tscheschichin, by repressing the chemical changes in the constituents of the body through which heat is produced.

⁷ Op. cit., 254.

This view is objected to by Rosenthal,⁸ on the ground that the facts are not universally agreed upon, and their interpretation is somewhat vague. Even the increased production of heat as determined by Wood, if admitted, may be regarded as the result of a modified circulation.

⁸ Op. cit., 442.

The preservation of a normal range of temperature in general is to be recognized as the result of variations in the relation of heat-production to heat-dissipation. The causes which influence this relation may act from without or from within, and are regarded as producing their effect by means of the vaso-motor nervous system. The causes which act from within are those concerned in the febrile elevation of temperature. Whether the latter is associated with, or independent of, inflammatory processes, the question of first importance relates to the modification of physiological conditions. The causes of the physiological production of heat and its dissipation have already been referred to, and the same elements demand consideration in the pathological range of temperature so striking in fever.

Relatively accurate inductions with regard to the origin of febrile heat were first rendered possible by the experiments of Billroth and Weber. These observers found that the introduction of putrid material into the circulation of animals produced fever. It was afterward shown that various substances, not necessarily of a putrid character, might produce the same result.

From measurements with the calorimeter of the heat produced, it was concluded by Wood⁹ that in the fever of pyæmic dogs more heat was produced than in healthy, fasting dogs, although less than in high-fed, healthy dogs. An increased production of heat in the fevered animal is thus obvious, as his capacity to receive and assimilate food is considerably less than that of a high-fed, healthy dog. The calculations of Sanderson, referred to by Wood,¹⁰ based upon the analyses of eliminated carbonic acid and urea, show that the febrile human subject produces very much more heat than the fasting, though less than the fully-fed, healthy, man.

⁹ Op. cit., 236.

¹⁰ Op. cit., 239.

An increased production of heat in fever is generally admitted, although it alone is not to be regarded as the essential feature in the elevated range of the temperature. The fasting man or animal under ordinary circumstances is not febrile, and an increased production of heat from full feeding in health, equal to that observed in fever, not being associated with fever, it is apparent that the retention of the produced heat is of importance for the existence of fever. Although it has been shown by various observers that more heat is dissipated during fever than in health, this increased loss is not in proportion to the increased production of heat. A persistent elevation of temperature is the necessary result. This elevation is subject to daily and hourly differences, as is the temperature of the healthy individual. These variations in the range of the febrile temperature are apparently due to an agency like that which dominates the course of normal temperatures—viz. a varying action of the vaso-motor nervous apparatus, as well as of that controlling the secretion of sweat, now permitting, now checking, the dissipation of the produced heat.

For the existence of the elevated temperature of fever, therefore, there is demanded the presence of an agent within the body which, as stated by Wood,¹¹ shall act "upon the nervous system which regulates the production and dissipation of animal heat—a system composed of diverse parts so accustomed to act continually in unison in health that they become, as it were, one system and suffer in disease together." It may be that there exists, as claimed by Wood and Tscheschichin, a heat-centre independent of the vaso-motor and other centres, through which heat is dissipated, or it may be, as maintained by Rosenthal, that the vaso-motor system alone is concerned in the regulation of temperature. Such action may be inhibitory or excitant, according to the views of the one or the other author, without affecting the main question as above stated.

¹¹ Op. cit., 255.

The elevation of temperature suffices to explain for the most part certain of the other phenomena of fever, as thirst, digestive disturbances, increased respiration, and emaciation. A coincident affection of various cerebro-spinal centres is demanded to explain the altered action of the heart and the numerous nervous symptoms which are to be found in fever. The agent producing such manifold effects is obviously no unit. It may be introduced from without or it may arise within the body, and its transfer to the nervous centres is undoubtedly accomplished through the circulation.

Among those agents which act from without are to be included the specific causes of infective diseases. It is probable that these produce the fever, as they occasion other symptoms of the disease, and their action may be regarded as direct, or indirect through the secondary products of their own vital changes. In the light of the existing facts the products of minute organisms developed outside the human body may give rise to fever when introduced, without the organism, into the body. The history of septicæmia contains numerous illustrations of the pyrogenetic properties of material produced in connection with wounded surfaces of the body exposed to the action of minute organisms. The introduction of blood of the same, or of a different animal, into the circulation of a given animal is followed by fever, as is the injection of considerable quantities of water into the blood-vessels. The same is true of various chemical substances.

It is further obvious that the agents producing fever may arise within the body. The fever resulting from the deprivation of water, and from the destruction of tissues, are instances of the probable origin of pyrogenetic substances from the rapid metamorphosis of tissues.

It is suggested by Samuel¹² that under given circumstances the fever may be sanatory. This view is based upon the probability that certain parasitic organisms are destroyed at such temperatures as may be produced within the body. The growth of the bacillus of malignant pustule takes place most vigorously at a temperature of 30.5° C. (95° F.), while its development is feeble at 40° C. (104° F.). The bacillus of tuberculosis, as shown by Koch, thrives at temperatures between 37° C. (98.6° F.) and 38° C. (100.4° F.), but its growth ceases at temperatures above 41° C. (105.8° F.). The spiral fibre of relapsing fever, which is present in the blood in great abundance at the beginning of the febrile onset, disappears at the close, the temperature being 42° C. (107.6° F.). It is not to be found in the intervals between the febrile paroxysms, but reappears a few hours before the recurrence of the fever. The history of intermittent fever suggests a similar relation between its cause and the febrile periods.

¹² Op. cit., 155.

The value of pain as evidence of inflammation is merely relative. Its existence depends upon the presence of sensitive nerves, and those inflammations are the least painful which occur in parts where such nerves are fewest.

The pain of inflammation is attributable to the pressure upon the nerves of that product of the inflammation known as the exudation. This pressure becomes all the greater the more abundant the exudation, or the greater the obstruction offered to its diffusion throughout the inflamed part. The intense pain resulting from inflammation of the fascia or of the periosteum is thus explained, while an inflammation of the loose connective tissue may be diffused over a wide area with little or no pain. In the chronic varieties of inflammation, where the exudation is but scanty, and its accumulation extended over a long period of time, there may be no pain during the entire course of the inflammation.

Swelling remains for consideration as the most important of the four cardinal symptoms. Like the others, its presence is not absolutely essential. It may exist at one time in the course of the inflammation, and may be absent at another. Even a diminution in the size of an organ may suggest the existence of an inflammation, for the yellow and cirrhotic atrophies of the liver give evidence, respectively, of an acute and chronic inflammation of this organ.

The swelling of an inflamed part is due to the presence of an increased quantity of blood, and lymph, and to the exudation. These constituents of the swelling are not of equal importance. Although the quantity of blood in the part is increased, no considerable swelling is produced, provided the flow of blood and lymph from the part be unobstructed. The current of lymph through the larger lymphatics may be greatly increased, yet a decided swelling be absent, unless there is an obstruction to the passage of lymph from the inflamed region.

The exudation is the most essential element of the swelling, and our knowledge of its origin and fate includes the most important features of the general pathology of the processes concerned.

The inflammatory exudation is represented by the accumulation, outside the blood-vessels, of material previously within them. The prevailing views concerning the manner of origin of this exudation, and its relation to inflammatory processes, are essentially due to the rediscovery by Cohnheim of the forgotten observation of Addison, that white blood-corpuscles pass through the apparently intact walls of the blood-vessels.

In the observation of the mesentery or other transparent part of a suitable animal, the changes taking place in inflammation are, at the outset, limited to the blood-vessels and their immediate vicinity. The vessels become dilated and the rapidity of the flow within them is soon diminished. In the veins particularly the white blood-corpuscles separate in considerable numbers from the general current and line the wall in constantly-increasing numbers, while the red corpuscles are borne along the middle of the stream. The white corpuscles stagnate, stick to the wall for a longer or shorter time, and often change their place, while the red corpuscles are in constant and progressive motion. In the capillaries a considerable number of white corpuscles are found in contact with the wall, but numbers of red corpuscles are associated with them. The formation of the exudation now begins by the passage of white corpuscles through the apparently intact wall of the veins and capillaries, especially of the former. Limited numbers, under ordinary circumstances, of red corpuscles also make their way through the walls of the capillaries. This is the phenomenon of emigration, and is associated with the amoeboid movements of the white corpuscles.

With the passage outward of the white and red corpuscles there is also the effusion of liquid material. Both the liquid and solid constituents continually escape and spread in all directions beyond the wall, following the course of the least resistance. It is probable that this course is defined by the pre-existing spaces within the tissues of the part, the lymph-spaces. The exudation is more abundant in parts richly provided with blood-vessels and in those containing the larger spaces; it is diminished where the vessels are less numerous or the surrounding parts more resistant, with smaller and fewer lymph-spaces. The resulting swelling is the less when ready opportunities for the diffusion and removal of the exudation by lymphatics and veins are presented, and when the material appears upon surfaces over which it may flow away.

The liquid portion of the exudation represents something more than the transuded blood-serum, and a certain practical importance results from the distinction drawn between an exudation and a transudation. Such a distinction is especially called for when the inflammatory or non-inflammatory origin of considerable quantities of fluid in the larger cavities of the body is concerned. From a recent contribution to our knowledge of this subject by Reuss¹³ the following information is derived: The percentage of albumen is always greater in exudations than in transudations, and is more constant in the former than in the latter. It increases with the severity of the inflammation, being highest in the ichorous forms, less in the purulent, and least in the serous exudations. When an inflammatory exudation is found to contain less albumen than usual, the existence of a transudation with secondary inflammation is suggested, or the exudation may have taken place in a hydræmic individual. A sufficient number of exceptions are met with, however, to interfere with the absolute nature of this test.

¹³ Deutsches Archiv für Klinische Medicin, 1879, xxiv. 583.

The coagulation of an inflammatory exudation apparently depends upon the contained white blood-corpuscles; the more numerous (within certain limits) these are in a serous exudation, the more abundant is the formation of fibrin. The cellular element likewise is that which in abundant liquid exudations characterizes them as purulent. Although it is generally agreed that most of the corpuscles of pus are emigrated white blood-corpuscles, it is not necessary to admit that all are of this nature. The cells present in an inflamed part include those pre-existing, as well as those which escape from the vessels. The former are the wandering cells of the connective tissues, as well as the fixed variety, the epithelial cells of the surface of a mucous membrane in addition to the subjacent connective-tissue cells. Amoeboid cells outside the blood-vessels have been seen to divide, and it is possible that such duplication may serve as the method of formation of a certain number of pus-corpuscles. The statements concerning the proliferation of the fixed connective-tissue cells and of epithelium are derived from appearances, and are interpretations of these appearances, not observations of a process.

The changes taking place along the walls of the blood-vessels being the feature of prime importance in the observation of the progress of an inflammation, numerous investigators have directed their attention to the determination of the nature of the changes in the vessel wall by means of which the escape of the corpuscles is permitted. Arnold represents the most strenuous advocates of the stomata theory, according to which the leucocytes pass through canals normally existing in the wall. By means of the silver method of staining, and by injections of various insoluble pigments into the blood-current, certain results are met with, which give color to the view that pores and canals are present upon and in the walls of the vessels, analogous to those found in the diaphragm. As the latter have been shown to be in direct communication with the lymphatic system of tubes and spaces, so the walls of the blood-vessels have been assumed to present similar channels of communication.

The prevailing views at the present time are in favor of the artificial nature of the stomata and pores in the walls of the blood-vessels. An increased porosity of the vascular wall in inflammation is necessary for the occurrence of the exudation, but such porosity is regarded rather as a physical condition permitting an observable filtration, and a filtration of solids as well as liquids.

In this connection reference should be made to the observation of Winiwarter, who has demonstrated that colloid material, a solution of gelatin, passes through the vascular wall in inflammation more readily—i.e. under less pressure—than through the normal wall of the blood-vessel.

The causes of inflammation are to be regarded as those which produce an increased porosity of the vessel wall without causing its death, for no exudation escapes from a dead vessel, its contents becoming clotted.

These causes may act from without or from within, primarily affecting the tissues outside the vessels, or exerting their action, at the outset, upon the wall itself. The usual histological relation of vessels and surrounding tissues is such that both are simultaneously affected. The occurrence of an inflammation in non-vascular parts, however, as the cornea, from irritation of its centre, the part farthest removed from the surrounding blood-vessels, shows that the affection of the vessels may be indirect as well as direct. This indirect action is to be regarded as taking place through the agency of nerves or through that of the nutritive currents. That nervous influence alone does not suffice to transmit the effect of an applied cause is apparent from the absence of inflammation of the cornea which has become anæsthetized by section of the trigeminus nerve. With the protection of the cornea from external irritation there is an absence of inflammation.

The consideration of the final symptom of inflammation, the disturbance of function, which has been added in recent times, belongs to special rather than general pathology. It varies according to the seat of the inflammation, the disturbed function of the brain or heart differing from that of the liver or kidney. The clinical importance of this symptom of inflammation is greater than of all the rest, as it is the one whose presence is constant and indispensable.

An inflammation may exist, as already stated, without heat, redness, or pain. The swelling may escape observation from the limited quantity of the exudation and other causative agents, or from the inaccessibility of the inflamed part to physical examination. The disturbance of function, however, becomes early apparent, and is present throughout the course of the inflammation. A knowledge of its nature enables the seat of the latter to be recognized, and its variations furnish a desired test of the efficiency of therapeutic agents.

The causes of inflammation may be divided into the traumatic, toxic, parasitic, infectious, dyscrasic or constitutional, and trophic.

The traumatic causes are those which act mechanically, producing an injury to tissues by pressure, crushing, tearing, stretching, and the like. Others represent modifications in temperature, thermic agencies, and include extremes of cold as well as of heat. The chemicals whose action is direct, as caustic, include a third variety of the traumatic causes. Such chemicals are applied to surfaces, cutaneous or mucous, and comprise the active element producing the perforating ulcer of the stomach and duodenum, as well as such substances as potash or sulphuric acid which may have been swallowed intentionally or accidentally.

The toxic group of causes is closely allied to the chemical variety of the traumatic agencies. It includes chemicals whose action is indirect, through absorption in a diluted form rather than from direct application in a concentrated condition. Such chemicals are derived from without, as arsenic, phosphorus, and antimony; or may be formed within the body, and the latter include the chemical products of putrefactive changes—in the urine, for instance—and, with considerable probability, certain of the active agents of blood-poisoning in septic diseases. It is not unlikely that some of the inflammatory affections met with among the so-called constitutional diseases, as rheumatism and gout, may owe their origin to the production of chemical substances within the body, excessive in quantity if not changed in quality.

The parasitic causes of inflammation are both animal and vegetable, and act upon the surfaces of the body or within its deeply-seated parts. Some of the animal parasites act locally at their place of entrance, while others produce but slight disturbances in this region, their effects usually resulting from the transfer of their offspring to remote parts of the body. The vegetable parasites are for the most part the various fungi, which act locally upon the skin or on those transitional surfaces lying between skin and mucous membrane. The resulting parasitic inflammations are known as favus, sycosis, ringworm, thrush, etc. The border-line between such parasitic diseases and those included among the infective diseases is somewhat arbitrarily drawn. Parasites in the limited sense act chiefly as foreign bodies, while the effect of minute vegetable organisms is rather that of ferments, in virtue of their products. Such a distinction is of relative value merely, as the micrococci and bacteria are capable of acting in other ways than by the production of septic material.

The infectious causes of inflammation are for the most part parasitic in their nature, although the discovery and identification of the parasite are in most of these inflammations assumed rather than demonstrated. The relation of the anthrax bacillus to malignant pustule no longer admits of a doubt, mainly in consequence of the researches of Koch. This investigator has been enabled to establish a definite etiological relation between the septicæmia of certain animals and accompanying minute vegetable organisms. His recent discovery of the bacillus of tuberculosis definitely removes the tubercular process from the group of dyscrasic or constitutional affections to that of the infective diseases. The constant presence of minute organisms in relapsing fever, leprosy, malaria, typhoid fever, diphtheria, erysipelas, and numerous other affections associated with, if not characterized by, inflammatory conditions, renders extremely probable the closest pathological relation between such diseases and a microscopic organism. That an inflammatory process may be regarded of infectious origin, it is necessary, according to Koch,¹⁴ that a characteristic organism should be found in all cases of the disease, and in such numbers and distribution as to account for all the phenomena of the disease in question.

¹⁴ Untersuchungen über die Aetiologie der Wundinfectionskrankheiten, 1878, 27.

These organisms may act in virtue of their growth and the consequent demand for oxygen, as seems probable in certain cases of malignant pustule, where the affected individual dies with symptoms of asphyxia. Their operation may also be like that of ferments, which produce chemical material whose effect may be remote from the immediate presence of the minute organism. They may likewise, in connection with their colonization in various parts of the body, act more immediately upon the walls of the blood-vessels, and produce that increased porosity which is so essential a factor in inflammation.

The discovery of the immediate cause of the various infective diseases, as measles, scarlatina, variola, cholera, dysentery, mumps, whooping cough, cerebro-spinal meningitis, and numerous other epidemic and endemic affections, still remains a question for the future. The constant association of microbia with any or all of such diseases is but one fact in connection with them, and such a discovery is to be regarded merely as a step forward, to be followed by others, each of which represents not only an advance, but confirms the position attained.

The dyscrasic or constitutional causes of inflammation are those which, though long established, appear less demanded as our knowledge advances. Regarded as the result of an alteration in the composition of the blood, it is obvious that such changes may arise from the introduction, from without, of wholly foreign material. The dyscrasia may also represent modifications in the relative proportion of the normal constituents of the blood. In the former series are included what, for the most part, have already been referred to under the toxic and infectious causes of inflammation. The dyscrasiæ from lead, alcohol, and the like belong to this series. Still more important are the poisons, the virus of tuberculosis and scrofula, of leprosy and syphilis. The dyscrasiæ known as anæmia, leucæmia, uræmia, icterus, and diabetes are to be regarded less as inflammatory causes than as predisposing conditions which favor the action of other groups of causes.

The trophic causes of inflammation are those whose action is supposed to take place through the influence of nerves. Although, as has already been stated, a faulty innervation of tissues is an important element in favoring the action of various inflammatory causes, there remain certain forms of inflammation where the disturbance of nervous action seems to be the essential feature. The occurrence of an acute peripheral gangrene soon after certain traumatic or inflammatory lesions of the brain or spinal cord, of articular inflammation following chronic affections of the cerebro-spinal axis, are instances in point. The origin and distribution of herpes zoster, the occurrence of sympathetic ophthalmia and symmetrical gangrene, suggest a predominant disturbance of innervation as the exciting cause. At the same time, it is desirable to call attention to the recent observations of MacGillavray, Leber, and others,¹⁵ which suggest that a sympathetic ophthalmia is due to the extension of a septic choroiditis along the lymph-spaces of the optic nerve. It is further apparent that in certain so-called trophic inflammations, as the pneumonia after section of the pneumogastric, and the inflammation of the eye following paralysis of the trigeminus, the paralysis of the nerve is a remote, rather than an immediate cause, of the inflammation. There still remain, however, a number of localized inflammations whose origin is so intimately connected with nervous disturbances as to demand, for the present at least, a corresponding classification.

¹⁵ Wadsworth's "Report of Recent Progress in Ophthalmology," Boston Medical and Surgical Journal, 1882, cvi. 517.

The course of an inflammation is often indicated by the predominance of certain symptoms, which, for the most part, indicate a condition of the individual acted upon rather than a peculiarity of the cause. The sthenic inflammations take place in robust individuals with powerful hearts and an abundant supply of blood. In such persons a strong pulse, high fever, and an injection of the superficial blood-vessels suggested, in former times, the necessity of bloodletting as the essential therapeutic agent. The sthenic form of inflammation was most commonly associated with pneumonia, where the obstruction to the passage of blood through the lungs was an important cause of the superficial injection of the blood-vessels.

The asthenic inflammations, on the contrary, are those occurring in feeble individuals, debilitated in consequence of pre-existing disease, exposure, or habits. A weak heart, low febrile temperature, and superficial pallor, characterize the asthenic inflammations, which show a frequent tendency to become localized in the more dependent parts of the body, the force of the circulation being too feeble to overcome the effect of gravitation.

In the typhoidal inflammations are associated those symptoms which are so prominent in the severe varieties of typhoid fever. These are the predominant symptoms: hebetude or low, muttering delirium, picking at the bed-clothes, involuntary evacuations, stertor, and the like. The nervous disturbances are associated with a feeble pulse and a dusky hue of the skin.

The constituents of an inflammatory exudation are frequently used as a basis of classification, and characterize the inflammation from the anatomical point of view. As the exudation is complex in its composition, the predominant element is made use of to designate the variety, and in doubtful cases a combined adjective indicates the presence of the two most abundant constituents. As the exudation is directly derived from the blood and contains serum in addition to white and red corpuscles, the serous, purulent, and hemorrhagic varieties of exudation naturally arise. The fibrinous and diphtheritic inflammations relate to the presence of membranes or false membranes. Finally, there are the productive inflammations, resulting in the new formation of tissue, and the destructive inflammations, where losses of substance occur.

Serous inflammations are most frequent in those parts of the body where the structure contains the largest lymph-spaces. The so-called serous cavities of the body offer the most favorable opportunities for the accumulation, as well as for the exudation, of the inflammatory product; then follow the regions of the larger lymph-spaces, according to the size and number of the latter.

The serous inflammations may also arise from the epithelial coverings of the body, as the cutaneous, alimentary, and respiratory surfaces. The serous exudations of the skin are those present in vesicles, blisters, or bullæ, which owe their limitation to the resistance offered to the spreading of the liquid inflammatory product by the coherent epidermis. Serous inflammations of the alimentary canal may assume a vesicular character, although, from the structure of its mucous membrane and the macerating influence of its contents, the vesicles are apt to be of an extremely transitory character.

The more important serous inflammations of the intestines are those manifested by profuse watery evacuations, the extreme form of which is to be found in cholera.

Serous inflammation of the lungs accompanies the more severe forms, and usually represents but a limited and circumscribed affection, associated with more abundant cellular and fibrinous products.

Serous inflammations of the peritoneum, pleura, pericardium, tunica vaginalis, and central ventricles often give rise to the presence of enormous quantities of fluid, whose partial removal from many of the cavities concerned by operative measures frequently represents a most beneficial result of treatment.

The smaller lymph-spaces of the connective tissue in various parts of the body are the frequent seat of the inflammatory oedema, so called, whose presence is an important indication of the direction assumed by a spreading inflammation, as well as a suggestion of the frequent virulence of its cause.

In general, the serous inflammations are to be regarded as less severe than other varieties, or as representing an early stage of what later may be otherwise characterized by a change in the nature of the products.

The purulent variety of inflammation is present when the exudation is abundantly cellular. As has already been stated, such cells are, for the most part, white blood-corpuscles. The purulent exudation, like the serous variety, may appear either on surfaces, when the term secretion is applied, or within the lymph-spaces of the connective tissue over a considerable space, when the pus is said to be infiltrated. When the infiltration is more circumscribed and the walls of the affected lymph-spaces are destroyed, so that adjoining cavities are thrown into larger holes, an abscess is present, from whose wall pus is constantly derived, while the inflammation is progressive.

The attention of the surgeon, in particular, has been directed to the isolation of the immediate cause of suppurative inflammation, and the modern, antiseptic, treatment of wounds is essentially based upon the view of the infectious origin of pus. The frequent presence of microbia in purulent exudation where no precautions are taken to exclude their admission, and their frequent absence or presence in minute quantities where such precautions are taken, have suggested that through their influence an inflammatory exudation is likely, if not actually compelled, to become purulent.

Whether the microbia or their products are the cause of most suppurative inflammations may be regarded as an open question. It is generally admitted, however, that, as a rule, an inflammation becomes purulent in consequence of the presence of an infective agent; in other words, that most pus is of an infectious origin and possesses infectious attributes. The labors of Lister in insisting upon the exclusion of all possible putrefactive agencies in the treatment of wounds have met with universal approval, and the basis of his treatment remains fixed, although different methods have been devised for its enforcement. His researches, and those stimulated by his work, have resulted in the establishment of principles which affect the whole field of theoretical as well as practical medicine.

Although most pus may be considered as due to the action of a virus introduced from without, and capable of indefinite progressive increase within the body, all pus is not to be regarded as of infectious origin. There are pyrogenetic agencies, like petroleum, turpentine, and croton oil, which, introduced into the body, produce suppurative inflammation without the association of microbia.

A bland pus is usually in a state of beginning putrescence, so that it is only relatively bland, and acquires extreme virulence when long exposed to putrefactive agencies. It is possible that those agencies producing an ichorous pus are the same or different from those present in bland pus. The ichorous exudation contains less corpuscles than bland pus, is more fluid, less opaque, strongly alkaline, of a greenish color, and of offensive odor.

In hemorrhagic inflammation the exudation contains large numbers of red blood-corpuscles. The occurrence of this form is sometimes associated with peculiarities of the cause, as is obvious from the epidemics of hemorrhagic small-pox, measles, scarlatina, and cerebro-spinal meningitis. It is also associated with peculiarities of the individual, as in such epidemics all cases are not equally hemorrhagic, and in scurvy the hemorrhages are attributable to the abnormal conditions to which the sufferers are exposed. Hemorrhagic exudations are also met with in those inflammations of serous surfaces accompanying the outcropping of tubercular and cancerous or sarcomatous growths. In all cases a hemorrhagic exudation represents a grave complication, and when found in serous cavities has a certain diagnostic, as well as prognostic, importance.

Fibrinous inflammations are characterized by the presence in the exudation of considerable quantities of fibrin. As the prevailing theory of the formation of fibrin demands fibrino-plastic as well as fibrinogenous material, both are to be sought for in the exudation. The latter is present in the liquid portion of the exudation; the existence of the former, as well as that of the ferment, is dependent upon the presence of the white blood-corpuscles. The more numerous these, within certain limits, the more abundant the formation of fibrin. As their death appears essential for the fibrinous coagulation, the latter is most constantly met with in those parts of the body where the white blood-corpuscles are quickest separated from influences favoring their life. The farther removed they are from the blood-vessels, the more likely is their early death. Fibrinous exudations are therefore frequent and abundant in cellular and serous (sero-cellular) inflammation of the great serous cavities of the body. The clotted fibrin appears as false membrane lying upon the serous surface, either smooth or rough, tripe-like, or as villosities projecting above the surface, and again as bands, fibrinous adhesions, stretching across the cavity and uniting opposed surfaces.

The frequent occurrence of fibrinous exudations on the mucous membranes of the larynx and trachea, accompanied by the suffocative symptoms known as croup, has led to the use of the term croupous inflammation as synonymous with fibrinous inflammation, and its application to various parts of the body where croupous—i.e. suffocative—symptoms are not in question. Croupous inflammation, when used, is to be considered as an anatomical term, indicating merely the production of fibrin, and, for the avoidance of confusion, it is preferable to substitute fibrinous for croupous when such inflammations are described.

The disease, croup, it is well known, may exist without a croupous—that is, fibrinous—inflammation, as is familiarly recognized in the constant use of the terms spasmodic, membranous, and diphtheritic croup.

Fibrinous inflammation of the mucous membrane of the larger air-passages is much more frequently met with than that of mucous membranes elsewhere, as of the intestines, uterus, and bladder. The pseudo-membranous inflammations of the latter tracts are more commonly the result of the catarrhal and diphtheritic varieties than of the fibrinous form. Fibrinous exudations on mucous surfaces, according to Weigert, can only take place when the epithelium is destroyed. Hence those causes which give rise to the destruction or detachment of the epithelium are alone capable of producing a fibrinous inflammation of mucous membranes, and a fibrinous laryngitis, trachitis, and bronchitis may result from the local application of such irritants as steam or ammonia, as well as occur in the diseases croup and diphtheria.

Fibrinous exudations may also be present within tissues, especially in those whose meshes are wide, provided the essential elements of coagulation are present. The coagulative necrosis of various organs, to be more fully mentioned hereafter, is closely allied to fibrinous clotting, the fibrino-plastic element being derived from the death of the parenchymatous cells of the part.

In the existence of a fibrinous pneumonia the conditions are somewhat analogous to those present in the fibrinous inflammation of serous surfaces and of the areolar connective tissue. There is present an abundantly cellular exudation, held in the place of its origin, the cells undergoing rapid death and surrounded by a wall whose superficial cells resemble in structure, if not in origin, the endothelial cells lining the smaller lymph-spaces of connective tissue, as well as the larger cavities within the same, known as serous cavities.

The diphtheritic inflammation is no more to be confounded with the disease diphtheria than is the fibrinous inflammation with the disease croup. Although diphtheria owes its name to the frequent presence of an apparent membrane, it may be said that the latter is not essential to the existence of the former. Diphtheria, like croup, is an affection in which various exudations may be present, and the anatomical product alone does not suffice in all instances for the recognition of the disease. In croup there may be a swollen mucous membrane, with a slight superficial mucous exudation, or a more abundant exudation of desquamated epithelium and mucus, as well as a fibrinous false membrane. In diphtheria the same varieties of exudation may occur, and in addition the diphtheritic exudation may also be present. The latter, however, is not limited to the disease diphtheria, for its presence is apparent in other mucous membranes than that of the air-passages, and in the pharyngeal mucous membrane in other diseases than diphtheria. A diphtheritic conjunctivitis, enteritis, cystitis, and endometritis are recognized. The cutaneous surfaces of the body may also furnish a diphtheritic exudation. The diphtheritic inflammations of wounds and of variolous eruptions are instances in point.

The characteristics of a diphtheritic inflammation are the presence within the tissues of a clotted exudation, which is associated with a defined swelling and death of the part. The exudation contains not only dead leucocytes and interlacing fibres, but is also provided with abundant granular material, much of which presents the well-known peculiarities of microscopic organisms. The apparent false membrane is thus dead, infiltrated tissue, which may be torn away from the continuous unaffected tissue, leaving a raw, rough surface, but not peeled from a comparatively smooth surface, as in other forms of pseudo-membranous inflammation.

The frequent association of a superficial false membrane, corresponding in area with that of the deeper-seated changes, in which cells and fibres may be present, is to be recognized. The diphtheritic process, however, is localized within, and not upon, the tissues affected. The diphtheritic exudation represents a local death, a necrosis, of the part concerned, and the result has frequently been compared with the death consequent upon the action of a caustic.

The immediate cause of a diphtheritic inflammation is now generally attributed to the action of microbia which enter the tissue from without, and in their growth beneath the surface produce not only the local, but also the remote, constitutional disturbances which are associated with a diphtheritic inflammation. The investigations of Wood and Formad¹⁶ point to ordinary putrefactive organisms as a sufficient cause for the diphtheritic inflammation of diphtheria, while other observers demand a specific organism as the exciting cause. The occurrence of diphtheritic inflammations in various parts of the body, in regions, as the intestine, where putrefactive processes are constantly present, and in the bladder and uterus, where the phenomena of putrefaction are often associated with diphtheritic inflammation, suggest the efficacy of ordinary putrefactive agencies in producing the latter. As all microbia found in putrefaction are not alike, and as the properties of certain, differ from those of others, and as our knowledge of the effects of all is but fragmentary, the characteristics of specific germs for a diphtheritic inflammation of one part of the body, or of all parts of the same, must still be regarded as not proven.

¹⁶ Research on Diphtheria for the National Board of Health, 1880, Supplement No. 7.

Productive inflammations are those which result in the new formation of tissues. One of the frequent products of inflammation is fibrous tissue, which, at first abundantly cellular, later becomes more vascular, and is finally transformed into a tissue whose fibres predominate over its cells. This formation of a cicatricial tissue demands further recognition when the termination of inflammation is considered.

In a more limited sense certain inflammations are called productive when multiple circumscribed new formations, as cancer, sarcoma, tubercle, and the like, arise in connection with the ordinary products of inflammation. Such new formations are of frequent occurrence in serous membranes, and a tuberculous pericarditis or a cancerous peritonitis, indicates that a growth of tubercles or cancerous nodules has taken place, in addition to a more or less abundant exudation with various proportions of serum fibrin and cells. This association of ordinary and transitory inflammatory products with the formation of more permanent tissues may be found within organs as well as upon surfaces. A tubercular arachnitis or lepto-meningitis presents the various products of an inflammation of the pia mater with an abundant formation of tubercles. In like manner, a tubercular pneumonia, or a tubercular nephritis suggests an association of neoplastic growth and inflammation, in the lung and kidney. Such a relation offers a basis for the theory in favor of the inflammatory origin of tumors, and is, in part at least, a cause for the frequent consideration of tubercles as mere inflammatory products, wholly cellular or cellular and fibrous, subject to the same modifications as take place during the course of ordinary inflammations.

Even if tuberculous and scrofulous inflammations are regarded as inflammatory processes, modified by a specific cause and by peculiarities of the individual, the cancerous and sarcomatous inflammations are still to be considered as representing an association of inflammatory disturbances and specific new formations, the cause of the latter not being the cause of the former. As ordinary inflammations of the regions concerned may take place in the absence of the neoplasms, so may the specific growth appear in the same regions without anatomical or clinical evidence of inflammation.

The classification of inflammation as to its products is supplemented by distinctions drawn with reference to the seat. The exudations may be superficial or deep-seated; they may lie within the cells, parenchyma, of an organ, or within the interstitial tissue of the same.

The product of superficial inflammations may lie on the surface, as in the case of inflamed mucous membranes, or immediately below the surface, as in numerous cutaneous inflammations, of which erysipelas may serve as the type. The term catarrhal, applied to superficial inflammations, carries with it the idea of displacement, flowing, of the exudation. The product of a catarrhal inflammation must be largely liquid, that such a displacement may readily take place, and the catarrhal exudation is chiefly composed of an excess of those elements which are present in the normal, physiological secretion from the membrane concerned. Mucus therefore represents a frequent constituent of the catarrhal exudation, and mucous as well as muco-purulent catarrhs of the gastro-intestinal, bronchial, genito-urinary, and other mucous membranes are recognized. The catarrhal inflammation of the respective membranes usually represents the mildest form, as it demands an intact epithelium, and a ready removal of the inflammatory product.

As the cause of a catarrhal inflammation may occasion a destruction of the epithelium or a necrosis of the mucous membrane, the frequent association of catarrhal with fibrinous or diphtheritic inflammations is obvious. In such cases the clinical importance of the latter varieties gives them the precedence in the designation of the inflammation. The retention of the catarrhal products is the frequent cause of permanent disturbances of a more or less serious nature. These result in part from the mechanical obstruction offered to the function of parts beyond the seat of obstruction, as pulmonary atelectasis; and in part from the changes taking place in the retained product. Purulent otitis media with its dangerous or fatal results, and gangrene of the lung terminating in septic pleurisy, are not infrequent instances of severe disturbances from putrefaction of the retained products of a primarily catarrhal inflammation. A cheesy degeneration of the catarrhal cells leads to a surrounding fibrous, or destructive, inflammation, with a corresponding diminution in the function of the organ affected.

Of the deep-seated varieties of inflammation, that requiring special mention is the phlegmonous form. This runs its course within the less dense fibrous tissue known as the areolar or cellular tissue. The term cellulitis is usually employed by English writers to indicate the seat and nature of the process, and although the use of the term cellular tissue is rapidly becoming obsolete, the convenience of cellulitis favors the retention of the latter name.

The exudation lies within the larger lymph-spaces, and is therefore sometimes designated as the result of a lymphangitis, the deep-seated, wider lymph-spaces being concerned rather than those more superficial. Certain forms of phlegmonous inflammation are of decidedly infectious origin, and, when seated subcutaneously, are known as phlegmonous erysipelas, being thus distinguished from the simple erysipelas, whose seat is defined by the small superficial lymph-spaces of the skin.

Infective forms of cellulitis are also frequently met with in the loose, sub-peritoneal tissue of the pelvis. The infectious element usually proceeds from the uterus, and excites the malignant oedema of the broad ligament, the septic parametritis, or the pelvic cellulitis, according as the lymph-spaces inflamed lie nearer the fundus or cervix, and as the direction of the current is upward toward the spine, or outward toward the sub-peritoneal lymphatics of the pelvic wall.

Parenchymatous inflammation is present when the exudation is taken into the cells of an organ, or when the changes dependent upon inflammation of an organ take place within its functionally important cells. Virchow originally used the term parenchymatous inflammation in contradistinction to secretory inflammation, the changes in the former occurring within the elements of the tissues, while in the latter the exudation made its appearance on the surface of the organ.

Parenchymatous inflammation is manifested by a degeneration of the cells affected. This may terminate in their destruction through the conversion of their protoplasm into fat-drops, fatty degeneration; although more frequently a simple accumulation of albuminoid granules (granular degeneration) occurs. The latter represents a transitory condition, from which a return to the normal state readily takes place. This form of inflammation is met with in those organs which present a sharply-defined contrast between the functionally important cells and the connective tissue which surrounds them. The liver, kidneys, heart, spleen, pancreas, and glands in general, are consequently the most frequent seat of parenchymatous inflammation.

Opposed to this variety is the interstitial inflammation. The exudation of the latter remains within the connective-tissue framework of the organ. It is essentially cellular in character, and the number of cells is comparatively small. With their presence and the possibility of their nutrition a permanent increase in the quantity of the fibrous tissue of the organ is permitted. This becomes relatively greater in the course of time, and the parenchymatous cells become degenerated and absorbed. Interstitial inflammations are likely to become chronic in character, and, from the outset, are usually associated with parenchymatous changes.

An important clinical distinction is drawn with reference to the duration of an inflammation. Acute inflammations are those whose course is rapid, whose progress is associated with graver disturbances of function, and with a greater prominence of the cardinal symptoms. The chronic forms occupy more time in their progress, the functional disturbances, though severe, are injurious more from their protracted persistence, than their temporary violence, while redness, swelling, heat, and pain are symptoms of trifling prominence.

The exudation in acute inflammation, if recovery takes place, is rapidly removed from the place of its origin, while in the chronic variety it tends to become a part of the region in which it lies, or, if removed, slowly disappears, and may be constantly replaced. Acute inflammations may become chronic, and the chronic variety is liable to acute exacerbations.

The distinction between acute and chronic inflammations is essentially one of convenience, and, when considered from the anatomical point of view, relates rather to the persistence of the results. These may be present as a variously modified exudation or as a degenerated condition of the parenchyma of the organ or tissue affected.

Inflammation terminates in resolution, production, or destruction.

For resolution to occur it is necessary that the causes of inflammation cease to act, either by their removal or their isolation, and that their results be removed. With the removal of the results there is often associated the removal of the cause. That such may take place it is necessary that the function of the vessel walls be so restored that the exudation ceases to escape. Inflammatory products already outside the vessels, if present on surfaces with external outlets, are carried along in the course of the excretions. If they lie within the cavities of the body not opening externally, their removal is accomplished through the medium of the circulating lymph and blood, by absorption. The liquid portion of the exudation becomes a part of the circulating fluids of the body. The fibrin is converted into a granular detritus, which eventually disappears from the place of its formation. The leucocytes may return to the blood-vessels or enter the lymphatics; the latter course probably being the one taken by the larger number of the corpuscles. Many undergo a fatty degeneration, and as they lie in lymph-spaces their conversion into an emulsion permits a removal of the mechanical obstruction to the flow of lymph through the spaces in which they were accumulated. The red blood-corpuscles are destroyed, their pigment being dissolved by the surrounding fluid and removed in the course of the circulation and excretions, or it becomes transformed into granules or crystals, which may remain in the place of their formation, or be transferred, within amoeboid cells, to remote parts of the body.

When the exudation is abundant, as in the great lymph-sacs of the body—the several serous cavities—and especially when the openings in the walls of these sacs are obstructed or the currents within them are feeble, absorption takes place with great difficulty, and demands a long interval of time. The fibrinous and cellular portion of such an exudation frequently becomes converted into a caseous mass, from a partial fatty degeneration and inspissation. This mass becomes isolated from the cavity in which it lies, usually at the most dependent portion, by the formation of a capsule of connective tissue. It may subsequently become infiltrated with lime salts, calcified, and thus remain comparatively inert throughout the life of the individual.

The productive termination of inflammation is manifested by the new formation of connective tissue. This tissue is variously designated, as the inflammatory process is limited to the surfaces of the body exposed to the air, or the surfaces of cavities and organs, or as it lies within organs or the deep-seated parts of the body. In numerous instances it becomes a permanent constituent of the body, and, as time is usually essential for its formation, its occurrence is indicative of a chronic, rather than an acute inflammation. Certain chronic inflammations are progressive in character, the production of connective tissue being continuous, with perhaps occasional intermissions, as in the chronic interstitial inflammations of organs and tissues. The new-formed tissue, which at the outset is rich in cells, becomes in time more fibrous, and associated with this change in structure is a physical modification, manifested by its shrinkage. This new formation may fill a gap resulting from the destruction of tissue in the progress of an inflammation, when it is present as cicatricial tissue—the scar which is usually met with upon the surfaces of the body or of certain of its organs. When opposed surfaces are united by the new-formed tissue, the term adhesion is applied; the adhesions being present as fibrous bands, cords, or membranes. The pericardial milk-spots and thickenings, the tendinous or semi-cartilaginous, indurated patches of serous membranes and of the intima of arteries, are all regarded as manifestations of a chronic inflammation of these tissues. With the localization of the inflammation in the outer walls of the bronchi and blood-vessels a thickening of the external sheath results, called a peri-bronchitis, arteritis, or phlebitis, as the case may be.

The new formation of blood-vessels is essential for the production and preservation of this connective tissue, and both arise from pre-existing tissues. Pus-corpuscles represent the simple cellular product of an inflammation, and their existence is but transitory. With the new formation of blood-vessels imbedded in abundant cells there exists a granulation-tissue, likewise transitory, but out of which arises the permanent fibrous tissue. The question is still mooted as to the part played by exuded white blood-corpuscles in the production of the permanent results of inflammation. It is generally conceded, especially since the observations of Ziegler, that they are capable of transformation into lasting constituents of tissue, into blood-vessels as well as into cells and fibres. Whether all the resulting permanent products of inflammation are dependent upon their activity, or whether the pre-existing fixed elements participate, is still to be considered undecided.

What, at present, appears most probable is, that from exuded leucocytes there arise, in the course of several days, larger cells—epithelioid or endothelioid—which are eventually associated with still larger cells, more irregular in shape, and provided with projecting filaments, giant-cells. Both varieties may result from the enlargement of leucocytes by fusion or by the assimilation of nutriment. The epithelioid cells eventually become fusiform or stellate, and their projections, as well as those of many of the giant-cells, become fibrillated. The fibrils of adjoining cells, becoming united, are thus transformed into a meshwork of fibrous bundles enclosing irregular spaces, while the nuclei of the cells, with the immediately surrounding protoplasm, remain upon these bundles as the permanent cells of the new-formed tissue. The blood-vessels arise from pre-existing vessels, chiefly capillaries, and probably are also formed from the cells present in the exudation. The former method is indicated by the projection of solid sprouts from the wall of a capillary, which may unite, forming arches, and communicate with sprouts from neighboring capillaries, thus forming bridges. Both arches and bridges then become hollowed and admit the circulating blood. Ziegler maintains that the projections of the larger epithelioid cells and giant-cells become elongated, and eventually fused with capillaries, or the projections from capillaries. When this fusion is accomplished the cells become hollowed, their cavities communicating with those of the blood-vessels. These epithelioid cells, whose formation and transformation are of such importance in the history of productive inflammation, are designated by Ziegler as formative cells, and are frequently derived from the exuded white blood-corpuscles, though not identical with them.

The inflammations not terminating in resolution or production, end in the destruction of the part. This result occurs when the nutrition of the inflamed territory is so diminished, by the changes in and around the vessels, as to become insufficient for its preservation. As the nutriment is derived through the blood-vessels, the more complete and the more permanent the stagnation in them the more likely is death to result. This event also depends upon the quantity and quality of the exudation. The more abundantly cellular the latter, the more likely is an abscess or ulcer to result.

As most abundantly cellular exudations are considered to be dependent upon the presence of putrefactive agencies, those inflammations of a predominant putrid character (gangrenous inflammations) are those terminating in destruction. The dead product is present as a slough or sequestrum, when dead soft or hard tissues are detached, entire or in part, from the living; or as a granular detritus contained in a more or less abundant liquid. The inflammatory process producing the slough and sequestrum is characterized as a gangrenous inflammation of soft parts or a caries of bone, while the process resulting in the formation of the granular detritus, and which has no necessary connection with putrefactive agencies, is called a softening, from the physical condition of its result.

Thrombosis and Embolism.

A blood-clot formed within a blood-vessel during life is called a thrombus. The entire process of which the thrombus is the essential element is designated thrombosis.

These terms were introduced by Virchow¹⁷ to avoid the confusion which resulted from regarding the process and result as synonymous with inflammation of the vessel. All writers, even at present, do not adhere to this strictness of meaning. For a thrombus of the vulva indicates a clot of extravasated blood within the connective tissue of the labium; in like manner, a vaginal thrombus is the effused and clotted blood in the loose connective tissue surrounding the vagina. These exceptions are gradually disappearing, and the word hæmatoma, tumor composed of clotted blood, is being substituted in both instances. A cancerous thrombus represents a mass of cancerous tissue whose growth is extended along the course of a vessel, its wall having been penetrated. In general, however, the term thrombus, unless otherwise qualified, is used as first stated.

¹⁷ Handbuch der Speciellen Pathologie und Therapie, Erlangen, 1854, i. 159.

Although thrombosis is commonly a morbid process, it is not uniformly so. Its physiological significance is illustrated by the part it takes in the closure of the umbilical and uterine vessels, after childbirth. The surgeon makes use of it in his efforts to overcome certain of the ill effects of amputation, and to accomplish a cure of such local diseases as aneurism, where it is deemed important to diminish the supply of blood.

The thrombus being a blood-clot, it is composed, like the latter, of fibrin and blood-corpuscles. It is presumable that the fibrinous part of a thrombus owes its origin to the same conditions which determine the presence of fibrin in blood removed from the vessels during life or in that within the vessels after death.

According to A. Schmidt,¹⁸ the blood and other fluids, in which clotted fibrin makes its appearance, contain two generators, called fibrino-plastic and fibrinogenous. The former is considered to be paraglobulin, a substance contained mainly in the white blood-corpuscles, while the fibrinogenous generator is held in solution in the plasma of the blood. When these materials are acted upon by a third, the fibrin ferment, clotting takes place and fibrin is formed. It is thought that the ferment is intimately connected with the white blood-corpuscles, for with the microscope coagulation is seen to advance as these become destroyed, and where the leucocytes are most abundant, there coagulation advances most rapidly. The elements of clotted fibrin are always present in circulating blood, but Brücke has shown that blood remains fluid, under ordinary circumstances, because of its constant contact with the normal vascular wall.

¹⁸ Rollett, Hermann's Handbuch der Physiologie, Leipzig, 1880, iv. 1, 114.

The general causes of thrombosis are those which produce an abnormal condition of the endothelium, a rapid destruction of the white blood-corpuscles, or a stagnation of the blood. With the presence of one of these causes there is often conjoined another, and the conditions under which they are present are conveniently used in the classification of thrombi.

Although stagnation of the blood is often an important immediate cause of its coagulation, it is apparent, from the investigations of Durante¹⁹ and others, that stagnant blood clots in the living vessels only when their endothelium is in an abnormal condition. With the co-existence of abnormal endothelium and stagnant blood, thrombi form with greater frequency and become more voluminous in a given interval of time.

¹⁹ Wiener Medizinische Jahrbucher, 1871, 321.

The importance of the death of white blood-corpuscles in the formation of thrombi is generally admitted, and is especially insisted upon by Weigert. According to the observations of Zahn, the nucleus of certain thrombi is the result of the death of these leucocytes and their accumulation upon an altered intima. The experiments of Naunyn, Köhler, and others show that a thrombus may be rapidly produced by the injection into the blood of fibrino-plastic substances, and of those through which free hæmoglobin is admitted into the circulation. The former may be expressed from a fresh blood-clot; the latter may be obtained by thawing frozen blood, or by injecting such material (bile-acids, for instance) into the circulating blood as rapidly destroys the red blood-corpuscles. Although Weigert lays special stress upon the destruction of white blood-corpuscles in the formation of the thrombus, it appears, from the experiments above referred to, that indirectly the destruction of the red corpuscles is also of importance.

Although largely made up of fibrin, a thrombus also contains blood-corpuscles, both red and white, and the appearance of the mass is modified according to the variations in the relative proportions of these constituents.

Zahn²⁰ divides thrombi, according to their color, into red, white or colorless, and mixed varieties. The red owes its color to a large number of red blood-corpuscles, while the white and mixed forms contain various proportions of white blood-corpuscles and fibrin and a diminished number of red corpuscles. The cause of this difference in the color of thrombi is to be sought for in their method of origin. When blood clots slowly in a dish, the heavier red corpuscles settle to the bottom, and the lighter white corpuscles form a superficial layer. Stagnant blood clotting rapidly furnishes a uniformly red mass. The red thrombus, like the red clot, is the result of the rapid coagulation of stagnant blood. The white thrombus, on the contrary, largely composed of white blood-corpuscles, represents a constantly increasing deposition of these from flowing blood. The mixed thrombi arise from a combination of both conditions, and are usually white at the outset. Thrombi formed in the heart and larger arteries are usually white, those in the auricular appendages and on venous valves are mixed, while red thrombi are more common in arteries and veins, since the conditions favoring their origin are more frequently met in such vessels.

²⁰ Virchow's Archiv, 1875, lxxii. 85.

Thrombi are frequently stratified, in consequence of the successive deposition of new layers of blood-corpuscles and fibrin upon a pre-existing thrombus. Circulating blood is therefore necessary for the stratification, and such thrombi are likely to be mixed in color. Unstratified thrombi are usually white or red, the former largely composed of agglomerated white blood-corpuscles so moulded and situated as to prevent a stagnation of blood in their vicinity, while the red thrombus is rarely stratified, since its formation demands a stoppage of the blood-current. Stratification is intimately connected with the enlargement or growth of the thrombus, which takes place from the surface exposed to the flowing blood, and which is greater or less according to the seat of the thrombus.

Thrombi are usually divided into those from compression, dilatation, traumatism, and marasmus; in all of which groups an abnormal condition of the endothelium is to be met with.

Thrombi from compression are frequently formed in veins, in the vicinity of growing tumors. Their presence is most constant when the vein is compressed between a resistant surface, especially bone, and the tumor. A compression of the smaller blood-vessels within an organ, as the liver or kidney, may take place in consequence of chronic interstitial inflammation, or the growth of cancerous or other malignant tumors in such organs. The production of this form of thrombus is sought for in the treatment of certain aneurisms by direct pressure, the resulting stagnation of blood being followed by a coagulation within the aneurismal sac.

Thrombi from dilatation are met with both in dilated arteries and veins. In aneurism and varix a slowing of the blood-current is present, and the intima of the diseased region is frequently in such an abnormal condition that a clotting of the blood readily takes place. The shape and situation of the dilatation are of importance in promoting the formation of the thrombus; the more pedunculate and the more voluminous the sac the more certain is the thrombosis.

Traumatic thrombi result from a direct injury to the vessel. This may be mechanical, as in the application of ligatures for the obliteration of vessels, the tearing of the veins during childbirth, and the infliction of wounds of every variety. The injury may likewise be chemical, from the action of caustics; somewhat analogous to which, are the effects of heat and cold. Allied to the traumatic thrombi are those which arise from acute inflammation of the intima extending from wounds or inflammatory processes in the vicinity of blood-vessels.

Marantic thrombi are those whose origin is attributable to that enfeebled condition of the body known as marasmus. This represents a weakening of the several functions, especially the circulation, respiration, and locomotion. Such may take place in disease or old age; and it is important to bear in mind those diseases in which marasmus is likely to arise, as thrombosis often proves a complication of such affections. Protracted fevers, as typhus and typhoid, puerperal diseases, the disturbances following surgical operations, chronic wasting diseases, as the tuberculous and scrofulous affections, are all likely to be accompanied by thrombosis. Stagnation of the blood, as well as alterations of the intima, is an important local condition in this variety of thrombosis, which is usually valvular or parietal at the outset, and may be both arterial and venous. Such thrombi are likely to become continued and to serve as a frequent source of embolism.

Thrombi are also divided into primitive, or autochthonous, and secondary varieties. The primitive thrombus is one which owes its local origin to conditions existing at the place of its formation and attachment. The secondary variety demands for its existence a primitive thrombus, whose place of development is remote in time and seat, and from which a part has been transferred to serve as the nucleus for the secondary formation.

The continued thrombus is often confounded with the secondary variety. Continuance is rather a quality of all thrombi, and is essentially growth, whether by lamellation or agglomeration. Such continued thrombi are extended in the course of the circulation, usually by a conical end, which is pointed toward the heart in the case of venous thrombi, but away from this organ when the thrombi are arterial.

Parietal and obstructing thrombi form another subdivision. The former arise from a limited part of the wall of the heart or blood-vessel, and project into its cavity. They are always in contact with flowing blood, and are white or mixed in color and primitive. They may attain a considerable size, and may eventually become obstructing thrombi. The latter are so called when they are of sufficient size to cause a considerable or total obstruction to the current of blood. In the last case the vascular canal is wholly filled by the thrombus. The shape of the older parietal forms is usually globular or pedunculate, owing to the growth in all directions except at the place of attachment; the obstructing thrombi are elongated.

Thrombi are also characterized by consistency and relative absence of moisture. A thrombus is brittle and dry as compared with a clot. In distinguishing between the two, difficulty arises only in the case of a thrombus which may have formed within a few hours before death. Post-mortem clots are moist, elastic, readily withdrawn from blood-vessels, and have a smooth and lustrous surface. Their color is either red, gray, grayish-yellow, or yellow, and is very often mixed. The lighter colors are due to causes which favor the precipitation of red blood-corpuscles before actual clotting takes place, or which occasion an increase of the white blood-corpuscles in fibrin. The thrombus becomes adherent to the vessel wall within a few hours, after its formation, in the case of the red thrombus, and at once, in the case of the white variety. A clot is never adherent, although it may seem so from its entanglement between the trabeculæ and tendons of the heart and the cavernous framework of venous sinuses. Such apparent adhesions are easily recognized by the smooth, shining, intact intima which is disclosed after the removal of a clot.

The thrombus not only tends to become enlarged by further depositions of material from the blood, but it also tends to become diminished in size from the contractile properties of its fibrinous constituent. Moisture is forced from the thrombus in consequence of this shrinkage, and its dryness is increased by subsequent absorption through the wall to which it adheres.

The changes eventually taking place in the thrombus are known as organization, calcification, and softening.

Organization is the transformation of the thrombus into a mass of fibrous tissue. This is accomplished, according to the researches of Baumgarten,²¹ by an outgrowth of endothelium from the intima of the vessel, the thrombus being absorbed as the growth of tissue advances. In the case of a thrombus due to the ligation of a vessel, a granulation-tissue also makes its way into the thrombus between the ruptured coats, and the new-formed fibrous tissue which replaces the thrombus becomes vascularized through this granulation-tissue. The vascularization of thrombi surrounded by unbroken walls is most likely to result from the extension into the thickened intima of new-formed branches of the vasa vasorum. Cohnheim claims that the organization of the thrombus may take place solely through the entrance of migratory cells, without any active participation of elements of the vascular wall. The canal is thus obstructed or obliterated by a fibrous tissue, which is pigmented or not, as the pre-existing thrombus contained red blood-corpuscles or not. These, when present, become transformed into granular or crystalline hæmatoidin, which may remain as a permanent constituent of the new-formed tissue.

²¹ Die sogenannte Organisation der Thrombus, Leipzig, 1877.

Even when the thrombus is completely obstructing at the outset, it is not necessary that a total obliteration of the vessel should result from its organization. It not rarely happens, either before or after the thrombus has yielded to the fibrous growth, in consequence of the shrinkage of the fibrin of the thrombus or of the contraction of the fibrous tissue replacing it, that gaps arise which become communicating canals. Through these the blood flows, and the vessel thus becomes only obstructed, not obliterated. The sieve-like tissue thus formed is spoken of as the result of a cavernous or sinus-like transformation of the thrombus. The length of time necessary for the removal of the thrombus and its replacement by fibrous tissue varies considerably. A vascularized granulation-tissue may be present within a week, and in the course of a month the thrombus may have been wholly removed, or a period of months may elapse and the thrombus and granulation-tissue still be present side by side.

The calcification of a thrombus takes place when the latter becomes impregnated with salts of calcium and magnesium. The condition may be present in thrombi which are exposed to a rapidly-flowing arterial stream, as well as in those which lie in venous pockets outside the course of the direct current of blood. The well-known phlebolites are examples of the latter variety. A calcified thrombus may be intimately united to the vascular wall, the results of calcification and organization being associated. Calcification and, in particular, organization represent favorable events in the history of thrombosis, as through their occurrence the process comes to an end, and disturbances, either local or remote, are prevented.

The softening of the thrombus, on the contrary, is always a source of danger. This is partly due to the nature of the products of the softening, whether bland or septic, and partly to the mechanical disturbances produced by the transfer of portions of the softened thrombus to remote parts of the body. All thrombi may become softened. When the process of organization advances normally, the softened parts are absorbed as rapidly as the formation of vascularized fibrous tissue progresses. If this formation is checked or stopped, the process of disintegration still continues. White corpuscles undergo fatty degeneration; red corpuscles give up their coloring matter and become converted, like the fibrin, into granules, and there results a granular detritus. This is present as a viscid, semi-fluid material, either red, gray, or yellow, according to the color of the thrombus. This simple softening is to be regarded as essentially chemical in character, and begins at the oldest portion of the thrombus and advances toward the periphery. Its products are capable of absorption without the production of serious disturbances, and are usually prevented from direct entrance into the blood-vessel containing the thrombus by the continuation of the latter from new coagulation or deposition upon its surface. The thrombus is thus extended as the softening progresses.

When the thrombus is comparatively free from red blood-corpuscles, the softened product, in consequence of its yellowish color, opacity, and viscidity, resembles pus. The so-called encysted abscesses projecting into the cavity of the heart, from its wall, are parietal and globular thrombi, in the interior of which softening has occurred. This form of softening is called simple or bland, as it is free from any evidence of local suppuration, inflammation, or general constitutional disturbance attributable to an absorption of poisonous material.

Septic softening is accompanied by general evidences of a blood-poisoning, and by the local phenomena of purulent inflammation. A suppurative thrombo-phlebitis or arteritis, occurs; that is, an acute inflammation of the wall of the vessel, corresponding in its origin to the seat of the thrombus, and characterized by the formation of pus. In the earliest stage the softened thrombus need not present products differing in appearance from those occurring in simple softening, but their effect is manifested by a rapidly-advancing inflammation of the vascular wall and by the evidence of septicæmia. Inoculation with such material produces a group of symptoms classified under the head of blood-poisoning.

Cohnheim lays special stress upon the presence of micrococci in the softened material, and it is generally agreed that the virulence of septic softening is connected with, if not due to, the presence of microbia. A septic softening may be induced by besmearing, with septic material, the outside of a blood-vessel containing a thrombus, and this form of softening is usually associated with those conditions favoring this relation. Such are the gangrenous wounds following surgical operations, the putrid inflammatory processes affecting the uterine wall after childbirth, the offensive inflammations of the middle ear, and the like. It is possible for a septic softening to occur independently of such contiguous or continuous relations with the surfaces of the body. It is considered, however, that the micrococci present in a softened thrombus must have obtained admission from without through one of the surfaces of the body, mucous or cutaneous, or through undiscovered abrasions of even intact surfaces of peculiar structure, as the alveolar wall or the intestinal mucous membrane. The thrombus is regarded as affording a favorable soil for the growth and activity of the organism.

The mechanical effect of a thrombus varies according to the venous or arterial seat of the same. Venous thrombi, as they are continued toward the heart, tend to become completely obstructing thrombi. In most parts of the body the venous anastomoses are so numerous that the obstruction of a vein is readily compensated for through the collateral venous circulation. When such a compensation is prevented by an extension of the thrombus from branch to branch, and finally to the trunk, an accumulation of blood in the peripheral veins must result. The remote parts become swollen, from the distension of the vessels with blood and the transudation of liquid, and eventually solid material from the blood. Venous thrombosis thus leads to oedema, and even hemorrhage. The more rapidly the obstructing thrombus extends, the earlier and more extreme is the oedema likely to become, while the slower the advance of the thrombus, the more favorable is the opportunity for an enlargement of the collateral vessels through which a sufficient flow of blood is permitted to check oedema and preserve nutrition.

Local mechanical disturbances from arterial thrombi are scarcely perceptible till obstruction is produced, and the results of arterial obstruction will be mentioned in detail in connection with the phenomena of embolism. Cardiac thrombi may occasion local disturbances from interfering with the action of the valves of the heart. Those thrombi which are attached to the valves, especially when calcified, may produce inflammation and aneurism of the opposed wall of the heart, by friction. The most frequent mechanical disturbance from the non-obstructing parietal thrombi of the heart and arteries results from the detachment of fragments and their transfer as emboli to remote parts of the body.

An embolus is a foreign body in a blood-vessel, usually too large to pass through the smallest capillaries, and the disturbances resulting from its presence are included under the term embolism. Although most emboli are detached portions of thrombi, any foreign body of suitable size may become an embolus. Such are tissues, as the pulmonary elastic fibres, fragments of diseased valves of the heart and of the intima of arteries, or portions of tumors growing into vascular canals. Others are globules of oil entering the torn veins when fat-tissue becomes crushed, or air-bubbles admitted through veins either wounded by instruments or opened after parturition by the dislodgment of their obstructing thrombi. Still others are granules of pigment derived from the coloring-matter of the blood, as in melanæmia, or introduced from without, as india-ink and cinnabar. The echinococcus has been found as an embolus, and it is highly probable that the cysticercus, the trichina, and other animal parasites may be disseminated as emboli over the body.

Vegetable parasites, like the bacterium and aspergillus, have also been included in the list, although the disturbances resulting from their presence are less due to mechanical obstruction than to colonization and growth. The experimenter uses the most various objects as emboli—bits of wood, rubber, and glass, globules of mercury, fragments of tissue, etc. Emboli are to be regarded as of arterial or venous origin. The arterial emboli are carried toward the capillaries, while venous emboli are carried toward the heart. The effect of both is partly or wholly mechanical, and partly due to the specific properties of the constituents.

The mechanical effect of an embolus is manifested by the obstruction it offers to the circulation, and the degree of the obstruction depends upon the size, shape, and density of the embolus and the nature and size of the vessel obstructed. An embolus may be so large as to be unable to pass through the valvular orifices of the heart. A long and narrow embolus might pass through a vessel which would not admit one which was short and thick. A jagged and dense embolus, by repeated blows or prolonged and forcible contact, might cause a weakening or rupture of the wall of a vessel, and thus produce an aneurism. Certain vessels (the terminal arteries of Cohnheim) furnish the sole supply of arterial blood to a district, and when they are obstructed, the results, to be mentioned later, differ widely from those taking place where free vascular anastomoses exist. When a trunk bifurcates, the larger branch usually receives the embolus.

Venous emboli are those which approach the heart by the peripheral veins of the body or the pulmonary veins, and the liver by the radicles of the portal vein. Emboli from the veins of the body are carried through the right side of the heart, if not so large as to be stopped at the tricuspid or pulmonary opening. As they enter the latter, they are carried along its course under the influence of gravity and the direction and force of the current, which are determined by the direction and relative size of the bifurcations of the artery, the right primary branch being larger than the left. Eventually, a point of the artery is reached whose diameter is less than that of the embolus, and the latter is stopped. This point usually corresponds with a place of bifurcation, and the embolus frequently rides the wall separating the branches.

Emboli from the radicles of the portal vein owe their most frequent origin to thrombi associated with inflammatory processes in the intestine, especially of the cæcum and vermiform appendage, to inflammatory processes in the spleen and obstruction to the flow of blood through the splenic artery, or to inflammatory changes proceeding from the kidneys. Such venous emboli are carried toward the heart, but are stopped on the way by the intrahepatic branches of the portal vein.

Arterial emboli are those which enter the left side of the heart from the lungs, which arise in the left ventricle or auricle, which may pass through an open foramen ovale from the right auricle, or which arise from the arterial wall. They are carried along the course of the arterial circulation, and are distributed over the different regions and organs of the body. Usually following the more direct course of the circulation, they are more likely to enter the abdominal aorta than to be carried toward the brain or upper extremities. Embolism of the carotids, especially of the left carotid, is more likely to ensue than embolism of the subclavians. Embolism of the coronary arteries is rare, while embolism of the splenic artery, the left renal and left iliac arteries, is comparatively common, and in the order mentioned.

When an embolus is found, or embolism suspected, the source is always to be searched for in those regions from which the affected part receives its blood. The source of arterial and portal emboli is usually found with ease, while the pulmonary embolus may come from so wide a region, the body-veins, that much time may be spent before its place of origin is discovered. An appreciation of the laws of the transfer of emboli renders such a discovery almost certain.

When the embolus reaches a point beyond which it cannot pass, the resulting disturbance depends essentially, as shown by Cohnheim, upon the presence or absence of arterial anastomoses beyond the place of obstruction. He gives the name terminal arteries to those which have no anastomosing arterial branches. These are met with in the spleen, kidneys, lungs, brain, and retina. If the obstructed artery is not terminal, the embolus may produce no further disturbance, the collateral supply of blood through the anastomoses sufficing for the nutrition and function of the part. If, however, the vessel is a terminal artery, and the embolus is completely obstructing, the supply of arterial blood must be wholly cut off from the region beyond the seat of obstruction.

If the embolus does not completely obstruct at once, it soon becomes sufficiently large for this result to ensue in consequence of a secondary coagulation. The rider assumes legs extending into the arterial branches beyond the place of obstruction, and a body which extends backward in the course of the circulation to the nearest branch. The result of the total obstruction of the vessel is to cut off the admission of arterial blood, producing a local anæmia. The contraction of the elastic tissues of the part propels toward the capillaries a certain quantity of the blood in the vessels beyond the point of obstruction, till this force becomes neutralized by the blood-pressure in the vessels surrounding the obstructed region. The anæmic part may subsequently become engorged with blood; it may die, a region of anæmic necrosis resulting, or the dead portion may become softened.

The engorgement of the obstructed territory has received the name of hemorrhagic infarction. A solid, wedge-shaped mass of a reddish-brown color is present, whose shape is due to the arborescent branching of the terminal arteries. According to Cohnheim, the engorgement of the region with blood takes place from venous regurgitation into the obstructed part, till the intravenous pressure is overcome by the resistance of the tissues in the region affected. The capillaries and larger vessels thus become distended, and an escape of liquid and solid constituents of the blood takes place. If the veins are provided with valves, or the venous regurgitant current is opposed by gravity, the hemorrhagic infarction is prevented or greatly impeded.

Litten,²² on the contrary, who has furnished a recent contribution to this subject, claims that the hemorrhagic results of embolism are not accomplished through venous regurgitation, unless increased venous tension is produced by coughing, vomiting, and like efforts. His experiments lead him to maintain that arterial blood from surrounding tissues is supplied to the obstructed region through the anastomosing capillaries. The force is not sufficient to drive the blood through the capillaries into the veins beyond, but an accumulation takes place in the capillaries, which become dilated and distended. The escape of blood-corpuscles and serum then takes place, the more freely, as Weigert²³ suggests, the larger and more numerous are the pre-existing spaces in the organ. Hence the infarction becomes the most characteristically developed in such organs as the lungs and spleen. Causes which obstruct the venous flow, as well as those which increase the arterial tension, promote the hemorrhagic infarction.

²² Untersuchungen über den hemorrhagischen Infarct., etc., Berlin, 1879.

²³ Virchow's Archiv, 1878, lxxii. 250.

A necrosis of the part whose direct arterial supply is cut off takes place when the structure of the organ affected is such that the admission of arterial blood is wholly interfered with. This is the case in the heart and kidneys, and to a less extent in the spleen. The opportunity is presented for the diffusion of a fibrinogenous fluid, lymph or blood-serum, through the cells of the organ which contains the other essentials for coagulation, and the dead part presents the characteristics attributed by Weigert²⁴ to death from clotting of the protoplasm, coagulative or ischæmic necrosis.

²⁴ Ibid., 1880, lxxix. 87.

Embolism of the cerebral arteries produces softening of the brain, not a hemorrhagic infarction or a yellowish necrosis. Weigert attributes this result, on the one hand, to the absence in the brain of abundant cells from which are to be had the ferment and fibrino-plastic material necessary for coagulation, and, on the other, to the closure of the spaces into which blood might collect by the rapid swelling of the tissues from the exuded lymph.

The hemorrhagic results of embolism are also met with in obstruction of branches of the mesenteric artery, which is considered by Litten, at least from its function and in connection with its sluggish current, to correspond with a terminal artery.

If the patient outlives these more mechanical results of embolism, the local changes taking place are those tending to remove the extravasated blood or the dead tissues. The embolus has become an obstructing thrombus, and its removal is accomplished in the manner already stated in connection with the subject of thrombosis. The wedge-shaped nodule of hemorrhagic infarction becomes decolorized through the absorption, in part, of the blood-pigment. That portion which is not absorbed remains at the site of the original lesion as granular or crystalline blood-pigment. A granulation-tissue is formed at the periphery, which extends into the infarcted region, very much as the endothelial and vascularized growth extends into a thrombus. Eventually, a patch of cicatricial tissue remains as the sole indication of the previous disturbance. This termination is rather suggested for the hemorrhagic infarctions of the lungs. The results are more apparent and more easily demonstrated in the case of the anæmic necroses, and the somewhat irregular depressions with wedge-shaped scars, seen upon the surface of the spleen or kidneys, call attention to the probable nature of the process giving rise to these results. A source of embolism must also be associated, that these scars may be regarded as of embolic origin. The embolic softenings of the brain are likewise represented in after years by losses of substance. The superficial, yellow patches or localized oedematous blebs, with corresponding atrophy of the convolutions beneath, call attention to a nutritive disturbance, as do cyst-like cavities in the deeper parts of the brain. Here, too, a source of embolism must be found, that the local destruction of tissue may be attributed to embolic obstruction of vascular territories.

When the embolus arises from a septic thrombus, the results differ from those above described. The embolus then carries not only mechanical possibilities, but also a virulent action. The latter is manifested by the rapid production of local inflammatory disturbances, as circumscribed abscesses and gangrenous destruction of tissue. Since emboli are frequently lodged near the surfaces of organs, a septic pleurisy, pericarditis, or peritonitis is the usual result of the dissemination of the virus contained in the embolus. This virus is similar in character to that found in septic softening of the thrombus, and, like it, is intimately connected with the presence of microbia. Whether the latter are specific in character, as maintained by Klebs and others, or whether they are to be included among those associated with putrefactive processes, still remains an open question.

The symptoms of thrombosis obviously depend upon the resulting obstruction to the circulation of blood, and in the case of primitive thrombi are gradual in their occurrence. The degree of mechanical obstruction is determined by the nature of the thrombus, whether parietal or obstructing, and by that of the vessel, whether provided with anastomoses sufficient to permit a compensatory collateral circulation or not. In the former case, if the thrombus is small and deep-seated, there may be no symptoms to indicate its presence. When the collateral circulation is insufficient to remove the blood from a region whose efferent venous trunk is completely filled with a thrombus, the phenomena of stagnation are produced. The part becomes oedematous, and red blood-corpuscles escape from the distended vessel. If the obstructed vein is superficial, the seat of the thrombus is indicated by the resistance and sensitiveness of the part. Characteristic disturbances of function are associated with thrombosis of the various organs of the body. If the cerebral sinuses are affected, mental disturbances arise; if a cardiac thrombosis is present, it is frequently accompanied by irregularity and feebleness of the heart. When the portal and renal veins are obstructed, functional disturbances arise in the parts from which they receive their blood.

The symptoms of embolism, like those of arterial thrombosis, are primarily due to anæmia. Suddenness is their characteristic in embolism, while they are gradual and progressive in the case of thrombosis. An embolic anæmia is complete or incomplete according to the terminal or anastomosing character of the obstructed vessel. The effect of the anæmia is to stop or check the function of the part, and varies according to the size and situation of the vessel. Hemiplegia, or perhaps aphasia or other evidence of localized disturbance, follows central embolism; angina pectoris, with a disturbed cardiac action, results from embolism of the coronary artery. Sudden suffocative symptoms, with open air-passages, suggest embolism of the larger branches of the pulmonary artery. A considerable hæmaturia often excites suspicion of an embolism of the renal artery, the hemorrhage coming from the vessels in the neighborhood of the obstructed region. Embolism of a large artery of an extremity is often localized by the sensation of a blow at the part, to be followed by absent pulsation, pallor, and coldness of the region beyond the place of obstruction.

The symptoms of the subsequent effects of thrombosis and embolism are to be inferred from what has already been stated with regard to the nature of the possible lesions. To enter into their detailed consideration would demand more space than is permitted, and would modify an established sequence or necessitate a repetition, which is undesirable in a systematic treatise.

Effusions.

The various fluids of the body are derived from without, and admitted into the blood-vessels. The physiological transudation through the walls of these vessels, in the main modified serum, becomes lymph as it appears in the several lymph-spaces. From the latter the transuded fluid either returns through the lymph-vessels to the blood-current or makes its appearance upon surfaces as secretions. These are variously modified as they pass through the specific cells of glands or as they are met with in the several closed cavities of the body.

The transudations thus occurring may vary in quantity within certain limits, the latter being somewhat indefinite, owing to the difficulties in the way of exactly measuring the fluid transuded. The greater part of this transudation is represented by the quantity of lymph flowing through the main lymph-trunk, and of the secretion from the glandular surfaces of a given region of the body; but that transuded fluid is not included which may return to the blood-vessels without being carried into the general lymph-current or secreted from a gland. Such a direct return may be considered to take place whenever the pressure upon the outside of the vessel wall is greater than that within the latter, or when the chemical composition of the fluids on the two sides of the filter permits endosmosis as well as exosmosis. This varying relation in the direction of the current through the vessel wall is likely to be of frequent, if not constant, occurrence in connection with the physiological processes taking place throughout the body.

The undue accumulation of the transudation in the various closed cavities of the body is known as dropsy, and the fluid present is regarded as an effusion or an exudation. These terms are often applied somewhat vaguely, now being used as synonymous, again as representing different conditions of the transudation, which are attributed to the varying conditions of its accumulation.

Exudation is more generally used when an inflammatory process is the cause of the increased transudation, while effusion is more strictly associated with causes other than inflammatory. In the present consideration this etiological distinction will be maintained.

To appreciate the conditions under which pathological accumulations of fluid, whether effusions or exudations, may arise, it is desirable to bear in mind the essential conditions which prevail in the occurrence of transudation, since the former are likewise chiefly derived from the blood and are transuded through the walls of its vessels. These conditions are largely dependent upon the laws governing the diffusion of substances through an animal membrane, the vascular wall representing the filter. As a living membrane its relation is dependent upon vital as well as physical conditions, and the former produce certain important modifications in the physical process of filtration.

The transudation through the vessels takes place chiefly through those with the thinnest walls, the capillaries, although it is probable that a certain degree of transudation may also occur through the walls of the smallest veins. The causes which are instrumental in promoting the circulation of the blood—viz. the contraction and dilatation of the heart, the contraction of the arteries, the inspiratory action of the thorax, and muscular movements throughout the body—are also essential in producing the flow of lymph; and the existence of pressure upon the hæmic side of the filter is the first feature of importance in occasioning the transudation. The constant removal of the transudation from the outer side results from the pressure being less in this position.

At the same time, an increase in the quantity of blood in the vessels is not necessarily productive of any considerable increase in the fluid transuded. Cohnheim calls attention to the experiments of Worm Müller, which show that a plethoric condition may readily be produced by the injection of quantities of blood into the circulation of animals, the amount of which cannot exceed twice the volume of the animal's blood without producing death. Although a temporary increase of the blood-pressure results, a return to the normal quickly follows. This is permitted by the propulsion of the excess of blood into the capillaries and veins, which become consequently distended, especially those of the abdominal organs. There is no increased transudation corresponding with the quantity of fluid introduced, nor is there any considerable distension of the blood-vessels of the skin, subcutaneous or intermuscular connective tissue. Such experiments show no permanent increase in the blood-pressure within the large veins if there is no obstruction to the admission of venous blood into the heart, presumably owing to their capacity for considerable distension.

Although experiments show that a simple plethora with great distension of the capillaries of the abdominal organs occasions no considerable increase of transudation, a different result follows a hydræmic plethora²⁵ induced by the injection of immense quantities of salt water into the blood-current—often six times as much liquid as the animal had blood. Here, too, the arterial blood-pressure shows no permanent increase, nor does that within the large veins become perceptibly increased till enormous quantities of fluid are injected. The blood flows through the vessels with increased rapidity in consequence of the diminished friction of the diluted blood, and an increased transudation begins at once. The various glands, salivary and gastro-intestinal, kidneys and liver, secrete more copiously, and the flow of a dilute lymph from the thoracic duct becomes greatly increased, while that from the cervical lymphatics becomes moderately accelerated. The lymph from the extremities, however, is no greater in quantity than that flowing from an animal in a perfectly normal condition. The localization of the increased transudation from the blood-vessels is further characterized by the abundant accumulation of watery fluid in all the abdominal organs and abdominal cavity, in the salivary glands and surrounding connective tissue, while elsewhere in the body the organs and tissues are almost invariably in the same condition with regard to moisture as are those of a healthy animal under normal circumstances.

²⁵ Cohnheim and Lichtheim, Virchow's Archiv, 1877, lxix. 106.

The importance of these experiments with reference to the causes of the transudation of fluid from the blood is obvious. The pressure upon the walls of the blood-vessels cannot become sufficiently increased to be accompanied with augmented transudation until limits are reached which are beyond the possibilities of occurrence in the human body. When such limits are attained in animals, the increased pressure, however great it may be, does not suffice to produce a general transudation, but one limited to the vessels of those parts of the body whose normal function is connected with too abundant transudation of fluid. A simple hydræmic condition of brief duration has been proven, by experiment, insufficient to give rise to increased transudation, neither increased secretion nor increased flow of lymph taking place. The inference from these experiments is that an increased transudation is more dependent upon conditions of the filter than upon those of blood-pressure. The absence of any observable changes in the filter leads to the assumption of an increased permeability, of physiological occurrence in certain parts of the body, as the chief feature in the occurrence of increased transudations.

Dropsy arises when the transudation is accumulated. As dropsical accumulations are transudations from the blood, essentially blood-serum with a diminished percentage of albumen, and as such blood-serum is practically lymph from its presence in the lymph-vessels, dropsical effusions are to be regarded as stagnant lymph. Such stagnations may be present in the small lymph-spaces within the connective tissue, or in the larger lymph-sacs, as the peritoneal, pleural, pericardial, and scrotal cavities. In like manner, the stagnation may take place in the cavities of joints and in those of the brain and cord, although the latter represent functional rather than structural lymph-canals.

The term oedema is applied to the accumulation in the connective-tissue lymph-spaces in general, while the term anasarca is confined to those cases where the subcutaneous lymph-spaces are concerned. The accumulation in the great lymph-cavities is known as ascites when peritoneal, hydrothorax when pleural, hydropericardium when pericardial, hydrocele when in the cavity of the tunica vaginalis, hydrocephalus if within the ventricles of the brain, and hydromyelocele when within the central canal of the spinal cord.

The accumulation of dropsical effusions may be considered as possibly resulting from an obstruction to the channels through which the transudation should flow, or from insufficient force to overcome normal obstructions, or from an abnormally increased transudation.

Lymph-channels are frequently obstructed, but no appreciable diffused retention of lymph results unless the thoracic duct is obstructed. This rare affection is followed by enormous distension of the thoracic and abdominal portions of the parts beyond the stenosis. Ascites and hydrothorax may follow, but not necessarily any considerable oedema of the peripheral parts of the body. As a result of the distension of the thoracic duct, rupture is not unlikely to take place, and the effused fluid contains chyle.²⁶

²⁶ Quincke, Deutsches Archiv für Klin. Med., 1875, xvi. 121.

That the obstruction is not followed by oedema is attributable to the innumerable anastomoses between the lymph-spaces, and also to the probability that a part of the transuded fluid returns to the blood-vessels when the obstruction is impassable.

The forces necessary to promote the flow of lymph have already been mentioned, and their entire removal is inconsistent with life. A diminution of their activity is more likely to result in a diminished flow of lymph than its accumulation, although a slowing of the lymph-current may represent a favoring element in the accumulation of an increased transudation.

The occurrence of dropsy with unobstructed lymph-channels, and in the presence of efficient agencies in promoting the flow of lymph, indicates the importance of an increased transudation as the chief element in the occurrence of a dropsical accumulation. An increased transudation, with resulting oedema, is readily produced by preventing the flow of blood from a part, and may be directly observed with the microscope. Cohnheim states that after a sudden venous obstruction, in case an efficient collateral circulation does not interfere, the capillaries and small veins become distended with stagnant blood and appear as masses of red blood-corpuscles. This distension results from the continuance of the arterial flow into the capillaries of the obstructed region under a pressure which is only neutralized by the resistance of the tissues and the transudation from the capillaries. Sotnitschewsky²⁷ shows that a concurrent paralysis of the vaso-motor nerves, as claimed by Ranvier, is unnecessary. The transudation through the capillary wall is increased, the flow of lymph from the part is accelerated, and oedema arises when the transudation is so much augmented that the calibre of the lymph-vessels is insufficient for its removal; and the greater this insufficiency the greater is the oedema. With the continuance of the arterial flow and intravenous resistance, red blood-corpuscles are forced through the filter, and form an important constituent of the effusion from venous stagnation.

²⁷ Virchow's Archiv, 1879, lxxvii. 85.

Although the existence of an increased pressure upon the capillary wall is obvious from the experiment referred to, there is no increased arterial pressure—rather a diminution—and the important element in occasioning the increased permeability of the capillary wall is the obstruction to the outflow of venous blood from the oedematous region. In consequence of the latter the arterial flow is followed by increased transudation.

Dropsies resulting from venous obstruction, as well as those following an obstruction of the thoracic duct or its branches, or of the several lymphatics of a part, are classified as mechanical dropsies. That from venous obstruction is the most frequent, and its seat may lie in the course of venous trunks or in the heart, lungs, or liver. The venous obstruction must be so situated that the stagnant blood is unable to find a ready escape through collateral branches. The more sudden and complete it is, the more likely is the effusion to contain considerable numbers of red blood-corpuscles.

In addition to the element of venous stagnation in producing increased transudation, the condition of the filter is of importance. The occurrence of oedema in chronic diseases, especially of the kidneys, and in those attended with protracted suppuration, continued hemorrhage, and the rapid growth of tumors, has usually been attributed to the watery condition of the blood, with a diminution of the albumen. Cohnheim, however, suggests that the condition of the vessel wall is of more importance than the contents as the immediate cause of the increased transudation. The more or less protracted action of various agents—temperature, insufficient oxygen, and diminished albumen—is likely to so modify the condition of the endothelium as to favor an increased permeability of the wall. Experiments show that a simple acute hydræmia produces no increased transudation, and that a chronic hydræmia, if connected with dropsy, is likely to be influential by increasing the permeability of the wall. Even in those cases where a hydræmia and an oedema co-exist, the localization of the latter is favored by obvious disturbances of the function of the capillary walls, as in case of the cutaneous oedema after scarlatina. In like manner, a feeble heart, favoring venous stagnation, and gravitation are of importance, as general causes, in promoting dropsy in hydræmic conditions.

The possibility of the occurrence of oedema through nervous influence is not to be denied. The localized and fleeting oedema of urticaria and erythema, the swollen lip and tongue in connection with digestive disturbances, are not to be explained by the two main factors of oedema—viz. venous stagnation and increased permeability of the vascular walls. Cohnheim refers to the rapid occurrence of oedema of the tongue as a result of irritation of the lingual nerve, and oedema is known to occur rapidly in cases of acute myelitis. A similar result follows the experimental destruction of the spinal cord, although the mechanism of its production is not apparent.

Dropsies are subdivided, as regards their distribution, into general and local forms. The causes producing the two varieties are essentially those already described. The causes of all local dropsies are not always to be regarded as the same. Regions which are the seat of mechanical dropsies are often affected by inflammation, with abundant serous exudation—the so-called inflammatory dropsy. The properties of the effusion and exudation are quite different, the former having a small percentage of albumen, but few leucocytes, with a corresponding absence of fibrin, and few or many red blood-corpuscles. The exudation, on the contrary, is highly albuminous, though less so than the blood-plasma; it contains numerous leucocytes and much fibrin; under ordinary circumstances there are but few red blood-corpuscles.

The local dropsies are often characterized by special terms. Hydrops ex vacuo is applied to the collections of fluid found in closed cavities with unyielding walls, as the cranium and thorax, or to the recurrence of fluid in cavities from which the same has been rapidly removed, in the absence of inflammatory disturbances. Collateral oedema is usually applied to the association of oedema with inflammatory disturbances, and represents an extension of the inflammatory process to the region concerned. Oedema of the glottis and circumscribed oedema of the lung are instances. The term hypostatic oedema is often used to designate the association of oedema and inflammation, the former caused by the latter, and to indicate the effect of gravitation in the localization of oedema from the general causes already mentioned.

Another localized oedema of interest, from its frequent occurrence and importance, is oedema of the lungs, often taking place toward the end of life, at times quite suddenly. This form has usually been attributed to increased transudation from arterial congestion or venous stagnation. The former view is directly refuted by the experiments of Welch,²⁸ who offers the explanation now accepted. With the obliteration of three-fourths of the arterial supply to the lungs of the animals experimented upon, no oedema resulted from the assumed collateral fluxion into the branches of the pulmonary artery which were left open. The obliteration of the same area of venous distribution was necessary before the occurrence of oedema. Oedema of the lungs was further found to result from a ligature of the aorta near the heart. The comparative frequency of oedema of the lungs in man, and the rarity of such extreme mechanical disturbances as those produced experimentally, led Welch to paralyze the left ventricle. The conditions as regards the pulmonary circulation then corresponded with those mentioned as causes for oedema from venous obstruction. The continued action of the right ventricle forced blood into the pulmonary capillaries, where it was compelled to accumulate in consequence of the inability of the left ventricle to receive and expel it. Welch consequently regards the immediate cause of this form of pulmonary oedema as a predominant weakness of the left ventricle. A weak heart does not suffice for the production of the oedema, since this condition is not found when both ventricles are alike enfeebled.

²⁸ Virchow's Archiv, 1878, lxxii. 375.

Degenerations.

The degenerations represent disturbances in the nutrition of the tissues of the body, in consequence of which their functions become impaired, if not destroyed. The latter result obviously attends the death of cells, which may occur in the course of the degeneration. The processes concerned are called necrobiotic by Virchow, as they represent vital processes leading to death. Although in many of them the cell is decaying during their continuance, its recovery is possible with the disappearance of the conditions which have transformed physiological into pathological processes. The degenerations affect intercellular substance as well as cells, and are called metamorphoses, infiltrations, or degenerations, as a transformation of normal into abnormal material, or the addition of extraneous substances, or the functional impairment of the part assumes the greatest prominence.

Cloudy Swelling, Albuminoid Infiltration, Granular Degeneration, Parenchymatous Degeneration.

Of the various modifications in the appearance of cells under pathological conditions, there is none, perhaps, more commonly met with than that known by the above terms. A granular appearance may be regarded as an essential characteristic of protoplasm, and is an attribute of cells of epithelial origin as well as of those which belong to other groups of tissues. The abundance of granules present in a normal cell depends largely upon its shape, size, and situation. These granules present various relations to chemical agents, some being soluble in alcohol and ether, others in acids and alkalies, and many of them, especially those met with in the form of degeneration now being considered, show from the various reactions that they are of the nature of albumen. Since their exact composition, in all instances, is undetermined, they are called albuminoid, and when in excess the cell is considered to be infiltrated with these granules, and the organ presents the appearances regarded as characteristic of an albuminoid infiltration. A granular cell becomes much more granular when it is thus infiltrated, and it is therefore a matter of difficulty to recognize from the appearance of certain single cells, as those of the liver or kidney, whether or not the number of granules present is abnormally increased. When, however, a large number of cells of any given organ contain more than the normal quantity of these albuminoid granules, the appearance of the organ becomes modified. In extreme cases the latter is swollen, doughy in consistency, with ill-defined structural details, and in all instances presents an opaque appearance. The term cloudy swelling is thus purely descriptive, and was applied by Virchow to designate the optical appearances of the condition in question. The granules, which disappear on the addition of acids and alkalies, are apparently either added to the cell or result from a precipitation within the same.

Frequently associated with these albuminoid granules are others, distinctly recognizable as globules of fat. An apparent increase of nuclei is often observed, and in certain organs, as the kidneys, the cells seem less coherent than is normally the case. The study of this condition in the kidneys is further of interest as indicating that the border-line between a parenchymatous degeneration and a parenchymatous inflammation is purely arbitrary. From similar exciting causes there may be associated, with the described alterations of the epithelial lining of the tubes, the exudation of albumen, the formation of casts, the desquamation of epithelium, and the presence of leucocytes within the tubules.

When the macroscopic changes are of moderate degree, and the disturbance of function relatively slight, while the concurrent alterations elsewhere, from the simultaneous action of the same cause, are predominant and characteristic of the disease, the condition is conveniently regarded as a degeneration occurring in the course of the latter, rather than an inflammation. The latter term, on the contrary, is to be applied when the granular infiltration of the cells is associated with other evidences of an inflammatory exudation, and when the pathological disturbances are to be directly attributed to the parenchymatous changes.

It is customary to speak of cloudy swelling as a nutritive change, and the condition may be induced by those causes which interfere with the nutrition of parts or of the whole of an organ. Many authorities regard this granular or parenchymatous degeneration as closely allied to fatty degeneration, since many of the causes which produce the one occasion the other. The former is often spoken of as an earlier stage of the latter, from the frequent association of the albuminoid granules with numerous globules of fat as a result of the more prolonged or more intense action of a given cause.

Organs which give evidence of a granular degeneration contain, as a rule, a diminished quantity of blood. This feature is usually attributed to the pressure of the swollen cells upon capillary blood-vessels. The anæmic organ obviously becomes still more cloudy, gray, and opaque in appearance from the diminished quantity or impoverished quality of the blood.

The granular degenerations of the heart, liver, and kidneys, as a whole, usually occur simultaneously, and afford a most important means for the post-mortem recognition of the infective diseases. The condition is therefore to be looked for in the exanthemata, especially in small-pox and scarlet fever, also in erysipelas, septicæmia in its manifold forms, diphtheria, typhoid and typhus fevers, cerebro-spinal meningitis, etc. A common feature in all these cases is the occurrence of fever, and it has been claimed that this element is the cause of the degeneration. In opposition to this view is the well-known fact of its presence in afebrile cases of poisoning from carbonic oxide, and its absence in certain cases of pneumonia and exposure to high temperatures.

The universal occurrence of cloudy swelling in fatal cases of the affections above mentioned leads to the inference of its presence in those instances terminating in recovery without obvious permanent impairment of the organs and tissues concerned. It is therefore agreed that the process may terminate in resolution—i.e. in a disappearance of the excess of granular material. On the other hand, its association, under circumstances, with fatty degeneration suggests as extremely probable that the latter condition may represent a result of the albuminoid infiltration. Even if this more serious issue exists, the possibilities are still at hand for an absorption of the degenerated material and a restitution of the destroyed protoplasm. The effect upon the individual is evidently determined by the persistence and dissemination of the condition, which, in turn, are controlled by the immediate cause and the peculiarities of the individual acted upon.

Fatty Metamorphosis, Fatty Degeneration, and Fatty Infiltration.

The fat which is present within the body under physiological conditions owes its origin primarily to the food taken. A diet which is abundantly fatty furnishes a direct source for much of the fat which appears accumulated in the various organs and tissues. Although it may now appear that such a statement needs but little confirmation, it is not long since the opinion prevailed that nearly all the fat in the body came from the hydrocarbons of the food. This seemed all the more plausible as the herbivora readily accumulated fat, although their diet might contain this element in very small quantities. Hofmann²⁹ made a decisive experiment with reference to the origin of fat from fatty food by feeding a dog, made lean by starvation, with bacon in abundance, but with little meat. In the course of a few days the greater part of the fat introduced was deposited within the tissues of the animal. Other experimenters have arrived at a similar result, and it can no longer be questioned that fat, accumulated within the body, owes its origin chiefly to the absorption of fat from the food taken.

²⁹ Zeitschrift für Biologie, 1872, viii. 153.

Another source for the fat of the body has long been suggested—namely, the albuminates of the food. In the admirable article on the formation of fat by Voit,³⁰ from which most of the information herein presented is derived, it is claimed that he and Pettenkofer were the first to prove the origin of fat in the body, under normal conditions, from albumen. This proof was an inference, however, although presenting a high degree of probability. Valuable evidence in the same direction was furnished by Kemmerich, who found that the milk of a cow during a certain period held more fat than was contained in the food; Subbotin and Voit have shown that more milk is secreted the richer the diet in albumen. Still other observers have furnished more decisive proof that fat is formed from albuminates.

³⁰ Hermann's Handbuch der Physiologie, 1881, vi. 1, 235.

Two sources for fat in the body under physiological conditions are thus recognized: 1, the free fat in the food; 2, the fat derived from the decomposition of the albuminates of the food.

Voit admits the possibility of the hydrocarbons serving as a third source, although this possibility is unnecessary in most cases. Should instances arise, however, where other sources for fat are found insufficient, the hydrocarbons must be regarded as filling the gap.

Fat which is taken into the body is considered to be either consumed or stored. That which is stored is chiefly accumulated in the great reservoirs—viz. the subcutaneous and perinephritic fat tissue, the mesentery, omentum, and bone-marrow—although it may be found elsewhere, in the fluids and tissues of the body. This accumulation serves as a source to be drawn from in case of need, and is called upon where the easily-decomposed soluble albumen is disposed of by the functional activity of the cells. An acting muscle demands food for its work, and consumes first the soluble albumen, then the fat. An excessive waste of fat is delayed by the decomposition of hydrocarbons, but the demands may become so great that albumen, fat, and hydrocarbons are consumed more rapidly and constantly than they can be supplied. It being, therefore, admitted that fat is formed from the albuminates, as well as from the fat of the food, the question readily presents itself whether fat may not be formed from the fixed albuminates of the body, especially from those contained within its cells.

It is well known that in the secretion of sebum the superficial cells of the sebaceous follicles contain fat in great quantity, while the deeper layers are comparatively free from any appearances indicative of the presence of fat. It is further admitted that when pus is retained for a time the individual corpuscles contain fat-drops in quantity and become transformed into fatty granular corpuscles. Eventually, the pus is transformed into a detritus in which fat-drops are found in great number.

Similar appearances may be present in the protoplasm of muscular tissue, the cells of the liver, kidneys, and gastric glands, when poisonous doses of phosphorus or arsenic are given. The occurrence of an acute fatty metamorphosis of the cells of various organs in new-born children has repeatedly been observed. The presence of fat in various organs of the body in pernicious anæmia, and in the heart in connection with stenosis of the coronary artery, is universally recognized. The abuse of alcohol, long-continued obstruction to the flow of venous blood, exposure to high temperatures, are all known to be conditions in connection with which fat-drops are found in the various cells of the body. The effects of poisoning with phosphorus and arsenic are of special importance, as showing that the abundance of fat present in the cells represents a result of the degeneration of these cells, since it takes place when the animal is deprived of food. Although there is an evident destruction of albumen, there is also a diminished elimination of carbonic acid and admission of oxygen. These facts are explicable on the ground that the fat present is not consumed, and the accumulation in the cells is evidence of this lack of consumption. The fat is not simply stored, as none is taken in, nor is any food received from which fat might be formed. Its presence, therefore, must be regarded as due to degeneration.

Since fat may be formed in the body as a result of the metamorphosis of cell-protoplasm, it is desirable to ascertain whether there are any means by which stored fat may be distinguished from that present as the result of a degeneration of the cell. The term fatty infiltration has been used to indicate the presence of stored fat, the latter being regarded as simply taken into the cell and retained for a longer or shorter time, without any necessary interference with other functions possessed by the cell.

In fatty degeneration, on the contrary, it is considered that the quantity of fat present indicates a corresponding diminution in the albuminates of the cell, and is connected with a diminution in the function of the latter, all the greater the more abundant the fat.

It is found that in fatty infiltration, as a rule, the fat is present in large drops, the size of the cell being increased in proportion to the quantity of fat present. Although there may be several drops present, they tend to run together, as is suggested by their different size, varying proximity, and the constant presence of a considerable quantity of protoplasm. In organs, on the contrary, whose function is seriously, even fatally, impaired, the fat, as a rule, assumes rather a granular form. Many minute fat-drops are present, and the cell is not particularly, if at all, increased in size. The more abundant the fat the less the protoplasm. Appearances are met with indicating a transition between cells with few fat-granules and those with many.

If the morphological appearances of fatty infiltration and of fatty degeneration were constant, there would obviously be little or no difficulty in determining the nature of the process manifested by the presence of fat. The exceptions occur both in fatty infiltration and fatty degeneration. In the cells of the liver of an animal poisoned with phosphorus fat makes its appearance in large drops, while in the heart and kidneys of the same animal the fat is present in a granular form.

During absorption from the intestine in the process of digestion fat is present in the epithelium in a finely granular form. When digestion is completed fat is no longer met with in these cells. The presence of large or small drops, therefore, cannot be regarded as a sufficient test of the origin of the fat. It is of equal, if not greater, importance to bear in mind the organ concerned.

In the heart, liver, kidneys, and gastric glands, as well as elsewhere, with the exception, perhaps, of the mammary gland, the presence of many small fat-drops in the cells indicates a degeneration of its protoplasm. The presence of large fat-drops, on the contrary, in the organs and tissues, with the exception of the liver, indicates an infiltration. Large fat-drops, then, may be present in the cells of the liver as the result of an infiltration or of a degeneration. In order to form a satisfactory opinion of the nature of the appearances in the liver in doubtful cases, it is important to note the condition of those organs which may be simultaneously in a state of fatty degeneration.

The accumulation of fat under physiological conditions is obviously brought about, on the one hand, by those causes which permit a free introduction, absorption, and deposition, and, on the other, by those which check its oxidation or elimination with the secretions of the body, as the bile, in which it may be present to a considerable extent. A diet rich in fat, or in albuminates readily converted into fat, offers a favorable element for the absorption of fat by the healthy individual. If the organism demands but little of this fat for oxidation, as in the case of the sedentary person, an accumulation is likely to occur. This may become so considerable that obesity results. Tissues in which normally but little fat is accumulated may become infiltrated to a large extent. The intermuscular fibrous tissue thus becomes loaded, and the activity, as well as the nutrition, of the muscles is impaired. This accumulation may be manifested not only in the voluntary muscles, but in the heart as well, which may present abundant sub-pericardial and sub-endocardial fat, the myocardium also being interlarded with streaks of fat, the so-called fatty infiltration of the heart. The abdominal walls may become thickened to the extent of a couple of inches, and the mesentery, omentum, perinephritic tissue, and liver may become enormously increased in weight from the mass of accumulated fat.

This infiltration of fat may take place under pathological as well as physiological conditions. It is apparent that those causes which check oxidation are likely also to prevent the consumption of fat, and it is well known that the destructive processes in the lung, grouped under the term pulmonary consumption, accomplish this result. Something more, however, is necessary than the obliteration of pulmonary blood-vessels and the destruction of an aërating surface. There may be, as in emphysema of the lung, a diminished respiratory and vascular surface, yet evidences of fatty infiltration, particularly of the liver, are wanting. It seems probable that the constant anæmia, with the loss of the blood-corpuscles, of pulmonary phthisis is an important additional factor in checking oxidation in this disease. This factor, it is needless to say, is not a necessary occurrence in pulmonary emphysema.

Litten³¹ has shown that when certain animals are exposed to high temperatures the appearances of fatty infiltration and degeneration are present in various organs of the body. He attributes the fatty degeneration to a direct poisoning of the red blood-corpuscles and a resulting diminution of the oxidizing processes.

³¹ Virchow's Archiv, 1877, lxx. 10.

It is universally admitted that in chronic alcoholism a fatty liver is frequently met with, even in the absence of those chronic interstitial tissue-changes usually characterized under the name cirrhosis. Alcohol is known to check the reception of oxygen and the elimination of carbonic acid, and, whatever other disturbance of cell-activity it may produce, its effect in favoring the accumulation of fat is directly attributable, in part at least, to this disturbance of oxidation.

In those conditions known as cachexiæ, the constant accompaniment of progressive and wasting diseases, as cancer, leucæmia, chronic dysentery, etc., a fatty infiltration, particularly of the liver, is a frequent accompaniment. A cachexia is dependent upon a complex series of processes, many of which tend to check oxidation, and in this respect is to be grouped with the conditions previously mentioned. That the associated fatty infiltration is intimately connected with the deficient oxidation is not to be doubted, although the agents producing this deficiency may vary in detail.

The causes which favor fatty degeneration are numerous, and the result represents one of the most serious conditions which can affect an organ. As oxidation represents the chief means of normally disposing of fat, so, pathologically, deficient oxidation favors the retention of fat due to degeneration. Were a constant renewal of protoplasm to take place, the degenerated fat might be displaced into the circulation or retained within the cell. If the latter event should occur, the result would be apparent as an infiltration, owing to the increased size of the cell, although the condition giving rise to the presence of the fat is a degenerative process. The importance of impairment of nutrition as the chief cause for fatty degeneration is thus obvious. It may readily be produced, experimentally, by measures which check the flow of blood to a part. The same measures necessarily prevent the presence of abundant oxygen, as fewer red blood-corpuscles are presented.

Fatty degeneration resulting from impaired nutrition is apparent in the heart in consequence of stenosis of its coronary arteries, in the kidneys as a result of interstitial processes obstructing the capillary circulation, in the brain from obliterative processes in the arteries at the base or within the organ, and in blood-vessels from the effect of age.

The cause of fatty degeneration may be general as well as local. In poisoning from phosphorus and arsenic the appearances in most of the organs indicate an actual destruction of protoplasm. Analysis of the secretions confirms this inference, as the production of urea is largely increased. Furthermore, there is less oxygen taken in and less carbonic acid eliminated. As has been previously stated, these conditions may be present in the starving animal. The fatty degeneration is thus easily explained as a metamorphosis of cell-protoplasm, and the deficient oxidation of the fat calls direct attention to its accumulation rather than elimination.

In acute yellow atrophy of the liver and in cases of severe jaundice fatty degenerations are constantly met with. That the origin and accumulation of fat in these affections is also due to rapid tissue-metamorphosis and checked oxidation is highly probable. Although the elimination of urea diminishes rather than increases, as shown by Schultzen and Riess, there are other links in the chain of retrograde changes, as the appearance of leucin and tyrosin, indicative of the extensive destruction of albuminates.

It is unnecessary in a work of the present character to call attention to all the possible circumstances under which fat is present in the body as the result of degeneration. Mention may be made of the acute parenchymatous (fatty) degeneration of new-born children, of the results of excessive bleeding, and of pernicious anæmia otherwise occasioned. The fatty degeneration of the uterus after parturition, of paralyzed muscles, and of tumors, the atrophic fatty degeneration of the liver in chronic passive congestion (nutmeg liver), are all well-known examples. To these may be added the fatty degenerations associated with amyloid and interstitial processes. It is apparent that in most of these instances the common features of rapid tissue-metamorphosis and deficient oxidation are present, and, being present, offer a ready explanation for the appearance of the fat.

The clinical importance of fatty metamorphosis requires consideration in connection with the description of the diseases in which its occurrence is a constant feature. As the presence of fat in cells is not necessarily pathological, so an interference with the function of the cell is not invariably implied by its presence. When its existence is suggestive of a local destruction of albuminates, a diminution of cell-activity is a necessary consequence. Such diminished activity must produce different results as the cells are those of muscles, of vessels, or of glandular organs.

Even if fat is found in cells under conditions favoring such a suggestion, it does not follow that the destruction of the cell must result. Not only is it possible that the fat may be reserved for eventual oxidation, and its place in the protoplasm be filled by normal constituents, but it is also possible that the fat may be eliminated, as such, from the body. The latter event is made apparent by the experiments of numerous observers referred to by Cohnheim, who have found free fat in the urine after its introduction into the venous current.

Cheesy Metamorphosis, Cheesy Degeneration, Caseation.

Virchow introduced the term cheesy metamorphosis, tyrosis, to designate the process resulting in the incomplete absorption of pus and the production of apparently similar changes in certain other occasional constituents of the body. The characteristic cheesy appearances were regarded as due to the inspissation of the material concerned, in consequence of the absorption of its fluid. With this inspissation there was frequently associated a partial fatty degeneration, and the cheesy matter represented dead material, which might undergo further changes, of which softening and calcification were the more important.

Inflammatory products, as pus and fibrin, were especially prone to become thus transformed, as well as other relatively transitory materials of new formation—viz. tubercle and parts of various tumors. The type of the cheesy metamorphosis was found in the enlarged lymphatic glands, commonly called scrofulous.

The importance of a clear understanding of the cheesy metamorphosis is now a matter of history. It is merely necessary to allude to the fact that these cheesy products were formerly regarded as indicative of the presence of tubercle, and were the tubercles. Tuberculization and the cheesy condition were synonymous terms, and their indiscriminate use led to much confusion with reference to the nature of tubercle.

Quite recently Weigert³² has called attention to the conditions present in necrosis resulting from the intermediate stoppage of the blood-current in a part. The effect is manifested, under favoring circumstances, by a cheesy appearance of the affected region, to which the terms decolorized hemorrhagic infarction, anæmic or ischæmic necrosis, have been applied. Weigert lays stress upon the existence of a coagulation of the protoplasm of the cells, with an early disappearance of the nuclei, as the essential feature of this form of necrosis, the conditions present being regarded as analogous to those met with in the coagulation of the blood. The term coagulative necrosis has consequently been introduced by Cohnheim to represent the process first fully described in detail by Weigert. The optical and physical properties of the ischæmic or coagulative necroses of tissue are often manifested as cheesy appearances, although the term coagulative necrosis includes conditions which do not present a suggestion of cheese. It is thus apparent that cheesy appearances may result in two ways: 1, by the inspissation of material in a state of partial fatty degeneration; 2, by a coagulation of the constituents of cells whose blood-supply is suddenly and completely cut off. In the more restricted sense these caseous appearances are regarded as indicative of a cheesy metamorphosis which arises by the former of these methods. Cheesy appearances, on the contrary, dependent upon the sudden death of a part, indicate an ischæmic or coagulative necrosis.

³² Virchow's Archiv, 1880, lxxix. 87.

Whatever may be the origin of the cheesy condition, the material presenting this appearance is liable to further changes, known as softening and calcification. The former event results from the soaking of the dead part with liquid, in consequence of which a detritus results. The softening usually begins at the oldest part of the cheesy mass, and advances toward the periphery. The sanatory evacuation of the emulsive detritus is permitted when a surface continuous with that of the external surface of the body is reached, as instanced by the escape of softened cheesy material from the lungs through a bronchus. The possibility of the complete removal of the dead mass is thus at hand, and an eventual obliteration of the resulting cavity may take place by an adhesive inflammation of its walls.

The complete absorption of the cheesy material of an ischæmic necrosis may occur by the extension into the latter of a granulation-tissue from the periphery. Whenever cheesy appearances are found on surfaces, as the degenerated tubercles of mucous membranes or the circumscribed necroses in diphtheritic inflammation or in typhoid fever, healing may be accomplished by their detachment as sloughs, a clean ulcer being left. Cheesy material is frequently encapsulated—i.e. imbedded in a layer of dense connective tissue, a condition which indicates a local cessation of the process through which the cheesy appearances arose. The same may be said of the infiltration of the cheesy mass with earthy salts—calcification—an event which will again be referred to in connection with the consideration of the general subject.

Hyaline Degeneration, Fibrinous Degeneration, Croupous Metamorphosis.

Certain of the conditions now regarded as indicative of a coagulative necrosis or a hyaline degeneration were previously described by Wagner as the result of a croupous or fibrinous metamorphosis. According to this observer, the cell-contents were transformed, under certain circumstances, into a substance resembling externally clotted fibrin. The formation of croupous and diphtheritic membranes, especially of the larynx, pharynx, and trachea, was thus explained, also the hyaline casts of the kidney.

The results of this metamorphosis presented a hyaline appearance under the microscope, and the term hyaline degeneration is now applied more especially to indicate the production of microscopic changes, while the hyaline appearances visible to the eye are rather included under mucous, colloid, or amyloid metamorphoses.

The limitations in the use of the term hyaline degeneration are but ill defined. On the one hand, there is included the transformation of muscular tissue, first discovered by Zenker; on the other, the various changes described by Recklinghausen and others, among which are embraced the results of Wagner's croupous metamorphosis. As the hyaline appearances are a frequent result of coagulative necrosis, these terms are frequently used to indicate the same condition, according as the optical or etiological features are uppermost in the mind of the observer.

The hyaline or waxy degeneration of muscular fibre described by Zenker represents a metamorphosis of the protoplasm of striated muscle in particular, although the fusiform cells of the muscular coat of the stomach and intestine may present a similar transformation.

The microscopic appearances are more characteristic than those visible to the naked eye. To the latter the muscle appears paler, more translucent, and homogeneous, and proves to be more brittle than normal. The muscular fibres are found with the microscope to be swollen, irregular in outline, the myosin transformed into flaky, glistening masses, without evidence of the normal transverse striation. These appearances have given rise to the term waxy degeneration, which suggests a possibility of confusion with the earlier recognized waxy degeneration of organs, due to the presence of amyloid material. The waxy transformation of muscular fibre, however, does not present the reaction with iodine characteristic of amyloid substance. The degeneration of the muscle is usually regarded as the result of a coagulation of the myosin, and it is claimed by Cohnheim that the latter takes place only in dead muscle, either during the life of the individual or as a post-mortem appearance.

The hyaline degeneration of muscular fibre is found in certain febrile diseases, as typhoid and typhus fevers, scarlatina, variola, and cerebro-spinal meningitis. It may also be met with when a muscle has been exposed to violence, as in the insane who have been placed under mechanical restraint. It has further been found in the vicinity of tumors, especially where muscles have been invaded by their growth. Cohnheim and Weil describe a similar condition in the tongue of frogs after ligature of the lingual artery.

The pathological importance of the above-mentioned degeneration of muscle is most prominent in cases of typhoid fever. The occurrence in this disease of the hæmatoma or blood-tumor of the rectus abdominis is thus explained, the degenerated muscle and its contained blood-vessels being ruptured. The muscles of the thigh and the diaphragm frequently undergo this degeneration; the change is more rarely met with in other muscles of the body.

Recklinghausen regards a hyaline substance, hyalin, as a normal constituent of cell-protoplasm which escapes in drops when the cell dies. Its presence indicates a diminution in the vitality of the cell from various causes. Under the microscope it appears as a sharply defined, highly refractive meshwork, enclosing spaces of irregular shape and size, in which are frequently found nuclei, more rarely cells or granules. Langhans has described this appearance as channelled fibrin. It has been met with in the placenta, diphtheritic membranes, blood-vessels, tubercles, and gummata.

The latest contribution to the history and nature of this form of degeneration has been furnished by Vallat,³³ from whose article many of the above data have been obtained.

³³ Virchow's Archiv, 1882, lxxxix. 193.

Mucous Degeneration, Mucous Metamorphosis, Mucous Softening.

Of the various degenerations presenting a colloid—i.e. gelatinous—condition, the mucous variety is one of the most striking. Its gross appearances may not differ materially from those to be described under the head of colloid degeneration, but the diagnostic characteristic of the change is to be found in the presence of mucin. The presence of this substance is readily detected by the addition of acetic acid to mucus, the effect being a fibrillated appearance of the latter, the fibres presenting a more or less parallel distribution. This fibrillation of mucus is regarded as the result of a coagulation of its mucin, previously held in solution by an alkali. Mucin is thus present in the body as a normal constituent, and, in the secretions from mucous membranes, owes its origin to the existence of epithelial cells, whether these represent gland-cells, as in the case of the muciparous glands of the bronchial mucous membranes, or whether they are superficial cells, as those of the gastric and intestinal mucous membranes.

In the origin of mucus as a secretion from glands Heidenhain³⁴ claims that a destruction of gland-cells accompanies the continuance of the secretion. At the outset, however, the mucin escapes from the cells, the latter remaining relatively intact. With the persistence of the secretion there results a destruction and a new formation of the muciparous cells. In the pathological production of mucus from mucous membranes, as in catarrh, there is no reason to doubt that the persistence of an irritation is the cause of abundant mucus, and that the latter is dependent upon the rapid formation and destruction of epithelial cells.

³⁴ Hermann's Handbuch der Physiologie, 1880, v. 64.

The origin of mucus from epithelial cells under physiological and pathological conditions being apparent, it readily follows that the epithelioid cells of tumors might be supposed to be liable to a similar metamorphosis. It is well known that cancerous tumors, especially those of the stomach and large intestine, are frequently met with, which present an abundant gelatinous material, more or less completely filling the spongy, fibrous meshwork. These are the alveolar, gelatinous, or colloid cancers.

The gelatinous or colloid material often gives the reaction of mucin, and the microscopic appearances of the tumor show that the jelly-like substance lies in that part of the tumor which corresponds with the position of the epithelioid cells. The latter are found in various stages of degeneration, the appearances being similar to those observed in the mucous degeneration of true epithelium.

The prevailing theory of the origin of cancer from epithelial structures readily suggests an explanation for the frequency of the mucous variety of cancer in connection with those parts from which mucus normally arises from the degeneration of the epithelium.

The mucous metamorphosis affects connective tissues as well as epithelium. The Whartonian jelly of the umbilical cord and the vitreous humor of the eye are known, through the investigations of Virchow, to owe their gelatinous condition to the presence of mucin. The latter lies in the intercellular substance; that is, between the cells. The appearance of these indicates no degenerative process, but the presence of mucin is obviously an essential constituent of the tissue. Whether this mucin represents a transformation of the gelatin of the intercellular substance, or a secretion from the fixed cells, or a metamorphosis of the migratory cells of the tissue, is not known. In mucous tissue, however, there is present mucin, wholly independent of any epithelial degeneration. Mucous tissue is present in the eye as a normal constituent of the adult, and in the umbilical cord as a normal constituent of the infant at full term. It is also abundantly met with in the subcutaneous and intermuscular tissues of the foetus. Its pathological occurrence in the adult as a circumscribed tumor, the myxoma, may also be mentioned.

A gelatinous substance containing mucin is found in the adult independent of the mucous tissue, but obviously arising from a transformation of intercellular substance. The most striking example of this occurrence is the cystoid softening of cartilage, especially of the costal cartilages of old people, the basis substance being transformed into a fluid containing mucin. A similar metamorphosis is of frequent occurrence in the intervertebral disks and in the destruction of cartilage in acute and chronic inflammations of the joints. The intercellular substance of cartilaginous tumors also becomes softened and converted into a liquid containing mucin.

In osteomalacia and in the absorption of bone the mucous degeneration of the bone-cartilage plays an important part. The lime salts are first set free, and the cartilage then undergoes a mucous degeneration; the product is either absorbed or remains as a liquid within cavities of large or small size. The mucous metamorphoses of fibrous and fat-tissues, likewise of bone-marrow, are well recognized instances of the occurrence of a mucous transformation of the intercellular substance of connective tissues. Finally, clotted fibrin, so often met with as the product of the inflammation of serous surfaces, may undergo a mucous metamorphosis, and, thus transformed, offer a suitable material for absorption.

Colloid Degeneration, Colloid Metamorphosis.

Laennec used the term colloid in a descriptive sense to indicate a gelatinous appearance, and for a long time its use was thus restricted. As the colloid appearances were found to differ in their chemical reaction, their distribution, and their pathological importance, and as the term was further extended to include appearances seen with the microscope, it obviously became necessary to subdivide the colloid series of changes according to the observed differences. Its use is now limited to those gelatinous conditions or appearances due to the presence of a fixed albuminate, homogeneous or finely granular, translucent, colorless or pale yellow, of varying consistency, which does not become fibrillated on the addition of acetic acid, and which does not change in color when acted upon by iodine. This albuminate is considered in most instances to represent the result of a transformation, a metamorphosis of cells, and is associated with an impairment of their function—a degeneration which is progressive, and leads, sometimes, to the destruction of the organ, as occurs in certain instances of colloid degeneration of the thyroid body. Usually, the process is limited, affecting particular parts rather than the whole of an organ. The reaction presented by a solution of sodium albuminate in the presence of neutral salts leads to the view that colloid material may represent a coagulation of an albuminous substance or substances under favoring conditions. The presence of colloid masses in the kidney thus meets with a plausible explanation.

The place of its typical occurrence is the thyroid body in certain cases of goitre, and it is early met with as a homogeneous substance replacing the granular cell-protoplasm. With its increase the latter disappears, and the entire cell is transformed into a homogeneous sphere. At times the colloid substance may be seen to project from the surface of the cell as a pale rounded clump. The aggregation of these clumps results in the presence of masses of various size, in which may be found granules of fat or pigment and crystals of cholesterin, which are accidental, not essential. Colloid masses are sometimes met with—in lymphatic glands, for instance—as concretions, mulberry-like aggregations of stratified colloid bodies, which may be infiltrated with earthy salts. Colloid material may eventually become liquefied, transformed into a sodium albuminate; and the presence of cysts in certain varieties of goitre is thus explained. The coexistence in the kidney of colloid accumulations and watery cysts has led to the view that the latter may, under certain circumstances, result from the former through the liquefaction of the colloid material. The same view is held with regard to the origin of cysts frequently met with in the choroid plexuses.

The colloid metamorphosis of cells is also to be found in the epithelium of mucous membranes and their glands, in the prostate, suprarenal capsule, sebaceous glands of the skin, and in the cells of certain tumors.

Amyloid Degeneration, Amyloid Infiltration, Waxy Degeneration, Lardaceous Degeneration.

The colloid appearances due to the amyloid degeneration of cells are of the greatest clinical importance from their frequent occurrence and the gravity of the symptoms connected with their presence. In amyloid degeneration there is the transformation of the cell-protoplasm into an albuminous material different from other albuminates found in the body. This transformation is at the expense of the functional activity of the cell, and the latter becomes inert. Amyloid degeneration represents no mere substitution, but an addition, since the affected tissue is increased in volume. The albuminate was called amyloid by Virchow in consequence of its color-reaction with iodine. Its method of origin is wholly unknown, never being found in the circulating fluids nor in articles of food. It is met with chiefly in the cell, although its presence in the intercellular substance of old people is recognized, and its occurrence in the midst of the thrombotic deposition on inflamed valves and in the results of inflammatory processes is also recorded.

At present the question is under discussion whether the amyloid degeneration may affect cells of the most varied character, or whether it is limited to those of connective tissues. Eberth³⁵ maintains that in all cases the amyloid disturbance is seated in the connective tissue. Kyber,³⁶ the latest investigator, in opposition to this view maintains that this affection is not limited to the connective tissue, but may also be seated in the parenchymatous cells of organs. Whether the one of these views is to exclude the other, or whether both are not correct, remains for future investigation to decide.

³⁵ Virchow's Archiv, 1880, lxxx. 138; 1881, lxxxiv.

³⁶ Ibid., 1880, lxxxi. 7, 111.

Wherever the amyloid material may be situated, the result is a transformation of the cells into a homogeneous, glistening, colorless material, which occupies more space than the original cell, and, when abundant, is accompanied with a loss of the primitive details of the cell-structure. This material is recognized by the color it presents when acted upon by iodine alone, by iodine and sulphuric acid, or by methyl-aniline. The first produces a reddish-brown color, the second a blue, and the last a violet or purple color. These reactions are all characteristic, and the first is of special value in the macroscopic recognition of the process, while the last two are of special importance in the microscopic recognition of the earlier stages of the affection.

With the advance of the degeneration and its dissemination, the organ affected presents, in the diseased portions, pale-gray, glistening, translucent patches, and becomes increased in size and density in proportion to the quantity of amyloid material present. The change appears primarily in the vessel wall or outside the same, and there results a diminution in the calibre of the vessels, with a lessened quantity of blood in the organ.

From the homogeneous and translucent appearance of the surface and the increased density of the tissues the resemblance to bacon or wax is suggested, and the terms lardaceous, bacony, or waxy degeneration have been applied. Notable differences in degree and seat occur in connection with the organs diseased. In the spleen, for example, the change may be limited to the arteries of the Malpighian bodies and their immediate surroundings. To this condition the term sago spleen is applied, the enlarged, rounded, translucent, and projecting bodies suggesting granules of boiled sago. The appearances of the diseased part are further affected by the association of other conditions, as the presence of fat or pigment. When fat is present, it is often to be regarded as a result of the gradual and progressive increase in the obstruction to the circulation of blood in the organ.

Although so little is known of the immediate cause of amyloid degeneration, its distribution in the various organs of the body is fully ascertained, as well as certain of the conditions which are likely to be followed by its presence. It is known to occur as a localized process in cartilage, in the conjunctiva, in certain tumors, cardiac thrombi, scars, retained inflammatory products, and renal casts. The causes of this localized appearance are wholly obscure, and little or no general inconvenience results. Its presence, however, on a large scale and in various parts of the body at the same time, is met with under such circumstances as indicate a distinct etiological relation. An appreciation of these circumstances is of importance, since their existence demands an investigation as to the probable presence of the degeneration. The organs thus affected are the spleen, liver, kidneys, and intestine. It is to their disturbance of function that the pathological importance of amyloid degeneration is to be especially attributed.

Other organs which may sometimes be affected are the lymphatic glands, pancreas, suprarenal capsules, omentum, uterus, bladder, prostate gland, heart, and thyroid body. In the case of a general diffused infiltration these organs are variously degenerated, now some, and again others, showing a more extensive alteration, while few or many may be simultaneously diseased. The longer the process has continued, the greater the degree of the disturbance and the larger the number of the organs infiltrated. Although, in general, a period of months and years may be demanded for these extensive changes, very serious disturbances may arise within a short time, and Cohnheim³⁷ records several cases which suggest that widely diffused amyloid degeneration may occur within a few months—in one instance in less than four months.

³⁷ Virchow's Archiv, 1872, liv. 271.

All that is at present known with regard to the etiology of this process applies to certain general diseases with which in the course of time it is likely to be associated. These have one element in common, that of chronicity, and are likewise the occasion of a progressive wasting of the body. Of these affections, that which holds the first place is chronic pulmonary consumption, especially that form in which extensive destruction of the lungs and ulcers of the intestine are present. Another disease whose effects are in like manner to be regarded as general is syphilis, and in the later stages of this disease amyloid degeneration is likely to occur, and often to represent by its resulting disturbances the immediate cause of death. Again, chronic suppurative processes, especially those due to disease of the bones and joints, are a frequent antecedent of amyloid degeneration. Finally, the process has been found in connection with leucæmia, chronic intermittent fever, rickets, gout, and certain malignant tumors. This last group, however, is one in whose sequence the degeneration is to be regarded as exceptional.

The clinical importance of this process is due to the resulting disturbances in the function of such important organs as the liver and intestines, the spleen and lymphatic glands, and the kidneys. The nature of these disturbances obviously demands detailed consideration in connection with the description of the diseases of the respective organs. It may be mentioned here that the infiltration of the walls leads to a narrowing of the calibre of blood-vessels, and thus a diminution in the supply of blood to the part or organ. The resulting impairment of nutrition becomes enhanced from the condition of the blood, which is impoverished from the simultaneous infiltration of the blood-making organs. The nutrition of the individual thus suffers as well as that of the immediately diseased organ. Fatty degeneration and atrophy of the parenchymatous cells of organs like the liver and kidneys is the constant result of long-continued and extensive infiltration of these glands.

Mention is intentionally omitted of the so-called amyloid bodies, corpora amylacea, considered in connection with amyloid degeneration in most text-books on pathology and pathological anatomy. They usually present a different reaction with iodine, their origin has but little in common, their distribution is for the most part unlike, and little or no clinical importance is to be attached to their presence.

Calcification, Ossification, Petrifaction.

When salts previously held in solution are precipitated under abnormal circumstances in the tissues of the body, the part is said to be calcified, ossified, or petrified. Although these terms are often used as equivalent, the last is to be regarded as more general than its predecessors, since it includes the deposition of other than the calcareous salts.

In the pathological ossification, as well as its physiological prototype, the carbonates and phosphates of calcium and magnesium are present in a specially formed tissue of the nature of bone-cartilage, whereas calcification occurs independently of such a new-formed tissue. The deposition of the calcareous salts takes place either in the cells or intercellular substance of living or dead tissues, when the terms calcification or ossification are applied, or as accumulations of various size in tissues or canals, which are known as concretions and calculi.

The immediate causes of the physiological deposition in the formation of bone are so obscure that only more or less probable explanatory theories are advanced, to all of which obvious objections arise. The causes of a pathological precipitation may be regarded as equally hidden. It is apparent, however, that old age usually furnishes the necessary factors. This in part may be due to the feeble nutrition associated with impairment of function in advancing years. In part it may be the result of the numerous opportunities offered in a long life for the occurrence of inflammation, the products of which are frequently infiltrated with calcareous salts. The latter are apparently kept in solution by the action of living cells, for, though presented to all in the fluids of the body, they are precipitated most constantly in dead parts or in the vicinity of those cells whose function is presumably lessened from disease or age. The solvent action of living cells is further demonstrated by the effect of the giant-cells in removing calcium salts from living or dead bone.

The causes of calcification are therefore to be regarded as local, depending upon a destruction or weakening of the cells of a part—conditions which are directly attributable to an interference with nutrition. The deposition of calcium salts thus represents a disorder of nutrition, and may be experimentally produced by agencies which occasion a necrosis of tissues.

Although the immediate causes of the precipitation of the calcium salts must be expressed somewhat vaguely, the places and effects of their accumulation are sufficiently well known, as are the resulting appearances. The presence of these salts in sufficient quantity produces a homogeneous, granular, strongly refractive appearance of the cell or intercellular substance, in addition to a greatly increased resistance to pressure. When muriatic acid is added to the affected part, the salts are dissolved, with the escape of abundant bubbles of gas when a carbonate is present, and with a rapid fading of the glistening appearance, without effervescence, when the salt is a phosphate. After the removal, the cell or intercellular substance is readily recognized, with such modifications in its appearance as may be due to the action of the strong acid. The parts in which this deposition or infiltration has taken place are either relatively normal in appearance or variously altered from disease, and the calcium salts are to be regarded as absorbed from the constituents of the food and deposited, or as taken up and transferred from the bones of the body. That both sources are drawn upon is obvious from the abnormal presence of calcareous material in the soft parts, in connection with increased density of the bones, as well as with a diminution in the density of the latter. The term calcification is more correctly applied to the presence of the salts in normal tissues other than bone, or in the products of disease not simulating bone-cartilage in structure. A pathological ossification is to be considered present when an actual new formation of bone has taken place so limited and so situated as not to suggest a tumor of bone, or when the calcium salts are deposited in a new-formed tissue whose structure stimulates that of bone-cartilage.

Tissues which may become calcified are, in the first instance, the connective tissues, and of these fibrous tissue and cartilage are especially liable. Epithelial, muscle—in particular the unstriped variety—and ganglion-cells may also become calcified. The frequency with which blood-vessels, especially arteries, are affected is such that it is regarded as almost normal in advancing years that calcareous material should be deposited within the vascular walls. A distinction is drawn between an ossification and a calcification of the blood-vessels. The former term should be limited to the osteoid plates so often found as circumscribed thickenings of the aortic intima, and which are obviously new-formed patches of fibrous tissue in which the calcium salts are accumulated. A calcified artery, on the contrary, is one usually of a size varying between that of the common iliac and the temporal arteries, whose wall has become rigid and unyielding, suggestive of a pipe-stem, from the presence of calcareous deposits in the muscular middle coat.

From the frequency with which the osseous plates of the aorta are associated with the fatty and fibrous changes in chronic inflammation of the intima, the so-called atheromatous degeneration of the same, it is customary to speak of the calcified artery at the wrist or temple as an atheromatous artery or as evincing an atheromatous degeneration. The common feature in the aortic changes and in the calcified muscular coat is the element of age. They are frequently, though not necessarily, associated. The one is the result of an inflammatory process productive of a new, fibrous, tissue in which the calcium salts are infiltrated; while the other is due to a deposition of the latter in the normal, pre-existing, muscular elements of the vessel.

Calcification and ossification of blood-vessels are frequent when the latter become dilated, as in aneurisms, whether these occur as circumscribed tumors or as a serpentine elongation and widening of the affected vessel.

Cartilage is also a tissue which presents a double relation to calcareous deposition. On the one hand, there may exist an ossification resulting from the extension of a growth of bone from the perichondrium into the cartilage. The structure of this bone presents all the details found in normal bone—lacunæ, lamellæ, and marrow-spaces. On the other hand, a section of the cartilage, especially the costal cartilages, may contain opaque, gray, or grayish-yellow patches, grating under the knife, which are wholly due to the presence of calcium salts in the hyaline intercellular substance of the cartilage. This calcification of the cartilage, which may also involve the capsules of the cells, is frequently associated with an ossification, although this relation is in no way essential.

Calcification of the placenta, of the fibrous framework of the lungs, of the mucous membrane of the stomach, or of the atrophied glomeruli of the kidney, are well-recognized instances of the infiltration of calcareous material in normal or atrophied tissues. On the contrary, ossification of the fibrous inflammatory products of the pleura, pericardium, and peritoneum are instances of a pathological bone-formation, analogous in its nature to that met with in the intima of the aorta. The fibrinous and fibrino-cellular products of the inflammation of serous surfaces are favorable positions for the deposition of calcium salts, as are thrombi arising from the walls of blood-vessels. The latter are rather instances of the calcification of dead parts, analogous to the members of the group which includes the formation of calculi and concretions, the calcification of the dead foetus in abdominal parturition, of cheesy lymphatic glands, and of cheesy material in the lungs and elsewhere. Finally, there remains the calcification of tumors of the most varied nature, the salts being present either in living or dead parts of the tumor.

Instances of the deposition in the tissues of other than calcareous salts are abundantly met with in gout. In this disease cartilage, ligaments, and tendons, bone-marrow, muscle, the endocardium and aorta, the membranes of the brain and spinal cord, the skin and kidneys, may contain deposits of acicular crystals and amorphous granules. Although these deposits are largely composed of sodium urate, calcium urate may be present with other salts, as sodium chloride and calcareous compounds. According to Ebstein,³⁸ the earthy salts in gout are deposited in necrotic patches of previously diseased tissue. The local conditions are therefore analogous to those concerned in the formation of chalky concretions.

³⁸ Die Natur und Behandlung der Gicht, Wiesbaden, 1882, 45.

Concretions and calculi are collections of earthy salts, the former lying within tissues, the latter being present in canals opening externally. Both represent the results of a deposition in and upon organic material, which is often an inflammatory product, at times surrounding a foreign body acting as the exciting cause of the inflammation.

The earthy matter of which the concretion is composed consists mainly of carbonate and phosphate of calcium, while the chemical properties of the calculi often vary in accordance with the nature of the secretion which flows by them. The salivary, pancreatic, intestinal, lachrymal, and prostatic calculi are chiefly formed of calcareous salts. These salts also are an important, if not the chief, constituent of biliary and urinary calculi. In the former pigment, bile acids, and cholesterin may also be present. Urinary calculi are of still more varied composition, containing not only the calcium salts, as the oxalate, phosphate, and carbonate, but also uric acid and the urates of sodium and ammonium, in addition to the ammoniaco-magnesian phosphate.

The infiltration with calcium salts may prove beneficial as well as injurious—beneficial under those circumstances where further changes might prove harmful, as in the softening of cheesy material or the maceration of a dead foetus in the abdominal cavity. The calcification of certain tumors, as the fibro-myoma of the uterus, is equally sanatory, the further growth of the calcified parts being thus checked. The calcification of an aneurismal sac may prove beneficial in strengthening a weakened blood-vessel.

The injurious effects are seen more particularly in case of the calcareous infiltration of the middle coat of arteries. Such vessels become converted into rigid and unyielding tubes at various parts of their course, and the nutrition of peripheral parts becomes correspondingly lessened. Hence, in great measure, the liability of old people to serious inflammatory processes from trivial irritation of peripheral portions of the body, such inflammations often terminating in gangrene.

The calcification and ossification of the cardiac valves and the calcification of attached thrombi, furnish frequent and constant occasion for disturbances in the functions of the heart, resulting in dilatation and hypertrophy, with the sequence of symptoms of chronic valvular endocarditis.

The great clinical importance of the presence of calcium salts in the circulatory apparatus is such that further reference in this place to its results is unnecessary, as its special relations are more important than its general features.

Calculi act as local causes of inflammation, and their presence is likely to be followed by ulceration, abscess, and stenosis, perhaps obliteration, of the smaller canals in which they may lie.

Pigmentation.

The pathological pigmentation of the body results, presumably, from the metamorphosis of the coloring matter of the blood or from the introduction from without of pigments insoluble in the fluids of the body. The former of these methods has recently been studied by Langhans³⁹ and Cordua,⁴⁰ and the present views of this subject are chiefly due to their observations, as well as to the earlier investigations of Virchow and others.

³⁹ Virchow's Archiv, 1870, xlix. 66.

⁴⁰ Ueber Resorptionsmechanismus von Blutergüssen, Berlin, 1877.

The hæmoglobin contained in red blood-corpuscles is considered to be composed of a coloring matter, hæmatin, combined with an albuminate, globulin. When blood is removed from the body the hæmoglobin is readily separated from the corpuscles by various agents, and is then dissolved in the plasma, which becomes lac-colored. This solubility of the hæmoglobin is of importance in connection with the absorption of extravasated blood. During the time necessary for this process to take place, observable changes are apparent in the color of the affected part when its seat is superficial, especially cutaneous. These changes in color are largely dependent upon the modifications undergone by the hæmoglobin.

It is well known that a yellowish discoloration of the general surface frequently takes place when extensive internal hemorrhages have occurred, constituting a form of jaundice (hæmatogenous) attributed to the presence of the coloring matter of the blood. As yet there has been no satisfactory chemical analysis of this diffused pigment, which if not hæmatin must be regarded as its derivative, although a coexistent increase of the urobilin in the urine has been observed. The association of the stained skin and urine, in the absence of causes favoring an absorption of bile-pigment, leads to the inference that the abnormal discoloration is due to the absorption into the circulating fluids of the body of a pigment dissolved out of the extravasated red blood-corpuscles. This view is confirmed by the microscopic examination of the latter, which discloses the presence of pale, shadowy, round outlines enclosing faintly granular material, which are regarded as decolorized red corpuscles. In the course of a few days glistening crystals and granules of a yellowish-red color make their appearance in the midst of the unabsorbed blood. The crystals are usually oblique rhombic prisms, varying in size from the larger symmetrical shapes to the more minute, apparently granular, forms. Acicular crystals are also to be met with, more yellow than red in color, and are sometimes present in great abundance, although they may be wholly absent. Virchow has applied the term hæmatoidin to these crystals. Owing to the resemblance in the chemical reactions of solutions of hæmatoidin and of the biliary coloring matter, bilirubin, and to the similar crystalline forms of the latter, it has been maintained that the two are identical. Late investigations indicate that solutions of crystals with the appearances of hæmatoidin are not invariably alike in their reaction. A solution of these in chloroform may become decolorized when acted upon by a dilute alkali, or it may not be thus altered. Bilirubin presents the former relation, while chloroform solutions of the coloring matter of the yelk of egg and of the corpus luteum, called lutein or hæmolutein, are not decolorized by an alkali. Although the crystalline forms of hæmatoidin and bilirubin are not to be distinguished, it is not to be conceded that the two substances are identical. As Maly,⁴¹ the latest writer on this subject, states, the term hæmatoidin is merely indicative of a microscopical picture. Although the identity of the coloring matter of the blood and of the bile is not admitted, the intimate relation of the two is not only suggested by the similarity of crystalline form, but by the relation determined between urobilin, bilirubin, and hæmoglobin. Urobilin is the coloring matter extracted from the urine in fever by Jaffé, and it has since been obtained from bilirubin by Maly,⁴² who has given it the name of hydrobilirubin. This hydrobilirubin has also been derived from hæmoglobin. According to Maly, this genetic relation between the coloring matter of the blood and bile, shown in the production of hydrobilirubin, is the only chemical evidence of the connection of the two pigments.

⁴¹ Hermann's Handbuch der Physiologie, 1880, vii. 155.

⁴² Op. cit., 161.

Hæmatoidin is to be regarded not only as directly derived from solutions of hæmoglobin, but as originating through the medium of indifferent cells. Langhans claims that this pigment is formed within movable cells which accumulate in great numbers in the vicinity of the blood-clot, and, in virtue of their amoeboid properties, take into themselves the extravasated corpuscles, entire or in fragments. The indifferent cell may become enlarged into a giant-cell, and then contain numbers of whole or disintegrated red corpuscles. In time these colored corpuscles and fragments become smaller, more glistening, and darker-colored, and eventually are transformed into granular or crystalline hæmatoidin. These granules may be set free by the fatty degeneration of the cell, or may be transferred within the cell to distant parts.

The diffusion and absorption of a solution of hæmoglobin, and the formation of crystals of hæmatoidin from the same or through the medium of cells, are supplemented by an apparent inspissation and condensation of the hæmoglobin. The resulting dark-brown pigment may remain at the seat of the hemorrhage indefinitely, and may be accompanied with reddish-brown flakes, which, as shown by Kunkel,⁴³ are composed of hydrated ferric oxide.

⁴³ Virchow's Archiv, 1880, lxxxi. 381.

Another feature in the absorption of extravasated blood is to be found on examination of the nearest chain of lymphatic glands. These may be seen swollen, of a dark-red color, and homogeneous surface. In density and color, as well as shape, they suggest the small supplementary spleens so frequently met with. These glands owe their change in appearance to the presence of large numbers of unaltered red blood-corpuscles which have entered the lymphatics traversing the region of hemorrhage. Within the lymph-glands they undergo a metamorphosis similar to that taking place at the part from which they were transferred. In the course of weeks or months there remains in the place of extravasation simply pigment, either as crystals or granules. Such pigment may remain for years imbedded within the tissues, or it may become absorbed, no trace of the original disturbance remaining. Its removal may take place presumably through a local solution of the pigment or the transfer of the granules or crystals by means of wandering cells to the nearest lymphatic glands or to the more remote parts of the body. An eventual elimination may occur through the secretions, especially the urine or bile, or there may result a deposition and permanent retention of the granules.

The investigations of Langhans are especially interesting, as suggesting efficient means for the production of pigment by cells whose function is intimately connected with pigmentation, as the cells of the rete Malpighii, of the choroid, and of certain tumors. The observations of Gussenbauer,⁴⁴ however, lead to the conclusion earlier advanced by Virchow, that pigment may be produced by the diffusion into cells, outside the vessels, of a solution of the pigment of the blood in the plasma of the latter. A precipitation of this dissolved pigment into granules is considered as eventually taking place.

⁴⁴ Ibid., 1875, lxiii. 322.

The method of origin of pigment thus described applies only to those discolorations which are unquestionably due to the metamorphosis of the coloring matter of the blood. Examples are furnished not only by the extravasation of blood on a large scale, but also by the escape of red blood-corpuscles in small numbers. Such an escape takes place from the pulmonary vessels in chronic obstruction to the admission of blood into the left side of the heart. The resulting brown induration of the lungs owes its color to the metamorphosed blood-pigment which is present as hæmatoidin in the interstitial tissue of the lungs, as well as contained within amoeboid cells in the alveolar and bronchial cavities.

It is probable that a similar transformation of hæmoglobin takes place in the spleen and elsewhere in melanæmia. In this condition the black granules of pigment, although differing in color and form from hæmatoidin, contain iron, and have received the name melanin. These granules are either free in the blood or are contained within the white blood-corpuscles. Their origin in the spleen is directly suggested by their frequent presence, often in considerable numbers, in the large, so-called splenic, corpuscles of the blood in the hepatic capillaries. Eventually, the pigment is found at more remote points in the circulation, and becomes fixed in the interstitial tissue of the various organs of the body.

The black pigment of the cells of melanotic tumors, also called melanin, is not to be directly traced to the hæmoglobin. Virchow⁴⁵ early called attention to the absence of iron in such pigment. Ferrated and non-ferrated varieties of melanin are thus to be recognized, the term being used in the same way as hæmatoidin, indicative of a microscopical appearance. A still further complication in the composition of melanin is suggested by Kunkel,⁴⁶ who has isolated a ferrated pigment from melanotic tumors. It shows, however, with the spectroscope, no relation to hæmatin, bilirubin, or hydrobilirubin. That its nature is similar to the normal pigment of the skin and choroid is suggested by the customary origin of the melanotic tumors in such pigmented tissues, and by the resemblance in appearance and reactions.

⁴⁵ Virchow's Archiv, 1847, i. 378.

⁴⁶ Ziegler, op. cit., 100.

That pigment of the most varied sort may be introduced into the body from without, and may remain indefinitely in the organism, is sufficiently well known from the results of tattooing. What is essential in such cases is, that the pigment shall be finely divided and insoluble in the fluids of the body. The most important of such pigmentations are those taking place through inhalation into the lungs. The reception by this channel of particles of soot is so common that it is most exceptional for the lungs of an adult to be free from the bluish-black discoloration due to this agent. Particles of coal-dust presenting the details of vegetable structure are met with in the lungs of individuals exposed to an atmosphere charged with this material. The worker compelled to inhale the dust of iron eventually accumulates a store of this substance, the quantity of which is essentially dependent upon the length of exposure, the degree of impregnation of the atmosphere, and the insufficient nature of the protectives employed.

Although a large part of the pigmentation under such circumstances is due to the direct presence of the foreign body, the appearances are also partly the result of consequent minute hemorrhages. The coal-dust and the iron-filings are often sharp and jagged fragments, which penetrate the delicate tissues, and the escaping red blood-corpuscles are acted upon by the amoeboid cells in the air-passages, with the consequent formation of hæmatin or hæmatoidin, as are the blood-corpuscles in larger hemorrhages. The inhaled pigment finds its way, either directly or by the agency of amoeboid cells, into the lymphatics and fibrous tissue of the lungs, and remains indefinitely either in the bronchial and pulmonary lymphatic glands or in the interstitial tissue of the lungs.

Attention may be here called to that pigmentation of the skin and deeper-seated parts of the body, especially of the kidneys, known by the term argyria. The long continued internal use of nitrate of silver, in former years so extensively employed, especially in diseases of the nervous system, results in the reduction of the silver and its deposition as minute particles in the tissues. Whether the silver is first reduced in the intestine and then absorbed, or whether it is absorbed as an albuminate and subsequently reduced, still remains an open question.

Although the pathological pigmentations form an extended series of alterations, the clinical importance of the condition may be regarded in many instances as trivial. The pigments resulting from extravasation produce no disturbance of function. The presence of bile-pigment does not account for the symptoms of jaundice. The clinical importance of melanæmia has perhaps been overrated. The earlier observations led directly to the inference that mechanical obstruction to the circulation in various organs might take place. The particles of pigment and the cells containing them were so numerous that this inference seemed quite probable. The evidence is still lacking, however, which proves the existence of definite symptoms and characteristic lesions as the result of the melanæmic condition.

The inhaled foreign bodies, as coal and iron, are productive of greater disturbances, and are well known as efficient causes in the production of chronic pulmonary consumption. The coal-miner's and scissors-grinder's phthises usually have, as an anatomical basis, catarrhal conditions of the aërating surfaces and interstitial inflammations of the pulmonary connective tissue. Mechanical obstruction to the aëration of the blood may also be present from the extreme quantity of the foreign material in the lungs.

Tuberculosis.

Until the investigations and discoveries of the past few years, the presence of tubercles in the various organs and tissues of the body had been regarded as the essential element of tuberculosis. The evidence to be presented in the following pages will show that the immediate cause of tubercles may produce other lesions as well, and that the presence of a specific virus as the efficient cause of whatever may be the lesion, rather than the existence of tubercles, is to be regarded as the characteristic feature of the disease tuberculosis.

The tendency of the present is to regard the latter term as including the various morbid processes connected with the origin, presence, and growth of a specific, organized virus, their dissemination, metamorphoses, and effects. Whether all those processes in connection with which the virus is found are due to the latter, or whether some may not arise and exist independently of the same, are among the questions whose answer is remote rather than at hand.

As the presence of the cause of tuberculosis is the test demanded by some authorities for the existence of the process, so the anatomical classification has depended upon the existence of the tubercle. The substitution of tubercle for organized virus in the general definition of tuberculosis represents the distinction between the anatomical and the etiological classification of this affection.

A tubercle was originally a small rounded body, a little tuberosity, and at the close of the last century the specific tubercle was distinguished from other rounded nodules.

Till the discovery of Villemin, the recognition of the tubercle was essentially based upon its anatomical characteristics. Previous to the studies of Reinhardt and Virchow these related to appearances, which were attributed to a deposition of material, scrofulous or tuberculous, from the blood or lymph. The idea was eventually maintained that this material formed the basis of a growth or new formation, and Virchow showed that the tubercle was composed of a tissue, of cells and intercellular substance, growing within and from pre-existing tissues. He classified the tubercles among the tumors as circumscribed new formations whose structure resembled that of granulation-tissue. The specific tubercle was, at the outset, minute, smaller than a millet-seed, submiliary, although indefinite numbers of these minute tubercles might be grouped together and form closely massed aggregations. From this agglomeration of single tubercles, and their frequent association with inflammatory products, both of which were prone to early death and transformation into a cheese-like mass, the extensive tubercular infiltrations of organs arose. The latter were regarded as a frequent cause of the wasting disease phthisis, which was either pulmonary, intestinal, or renal according as the lungs, intestine and mesenteric glands, or kidneys were the predominant seat of the tubercular growth.

The histological features of the tubercle were further investigated by Wagner,⁴⁷ who described the resemblances and differences of the structure of the tubercle and the lymphatic gland. Schüppel⁴⁸ soon after published his monograph, essentially confirming the statements of Wagner. According to these observers, the typical tubercle, as found in lymphatic glands, presents essentially the same peculiarities of structure when seen elsewhere in the body. This structure consists of a non-vascularized network of fibres, in the meshes of which cells are imbedded. The fibrous network resembles the reticulum of a lymphatic gland, and nuclei are often found at those points where the fibres are united. This appearance has suggested that the network is formed of branching and anastomosing cells. Within the meshes are three sorts of cells—viz. giant-cells, epithelioid (endothelioid) cells, and small, round, indifferent cells. One or several giant-cells, each with its abundant nuclei, lie near the centre of the tubercle or are diffused throughout the same. These are usually immediately surrounded by the large epithelioid cells, with one or more nuclei, which are often so numerous as to compose the greater part of the tubercle. The indifferent cells, resembling lymph-corpuscles, occur singly or in groups, distributed throughout the tubercle more abundantly at the periphery, between the cells previously described, and with them completely fill the spaces of the fibrous network.

⁴⁷ "Das tuberkelähnliche Lymphadenom," Archiv der Heilkunde, 1870, xi. 6; xii. 1.

⁴⁸ Untersuchungen über Lymphdrüsen-Tuberkulose, 1871.

Although the typical tubercle is thus constituted, the structural features depend somewhat upon its age. It is generally admitted that the freshest tubercles, as found in the external coat of the smaller arteries of the pia mater, are composed of little else than a circumscribed accumulation of small, round cells, without a distinct reticulum. The giant-cells, the epithelioid cells, and the well-characterized reticulum appear as the tubercle increases in age. It is thought probable that the giant-cells represent the agglomeration of the small, round cells in pre-existing cavities, lymphatics, blood-vessels, or secretory canals. The epithelioid cells in like manner are considered to result from the enlargement or fusion of the smaller cells, while the reticulum represents either a secretion from, or a transformation of, the cellular elements of which the tubercle is composed.

The subsequent history of the tubercle is dependent upon its metamorphoses. These are known as cheesy degeneration, calcification, and fibrous transformation.

The absence of blood-vessels, already stated, and the abundantly cellular nature of the growth, with the possible action of micro-organisms, result in a tendency to the early death of the cells and a necrosis of the tubercle. This is the cheesy degeneration, and is regarded as a form of coagulative necrosis, which begins at the centre, advances toward the periphery, and results in the transformation of the gray into a yellow tubercle. This termination in cheesy degeneration likewise affects inflammatory products surrounding the tubercle, and even relatively normal tissues in which numerous tubercles may lie. This cheesy material either softens or becomes infiltrated with lime salts, calcified. The softening of the tubercle results in the formation of a material capable of removal as a discharge from the surfaces of the body or by absorption through the lymphatics and blood-vessels. In the former event ulcers arise upon, and cavities communicate with, the surfaces of the body opening externally.

The cheesy material frequently becomes calcified, thus remaining as a comparatively inert mass. The earthy salts may be diffused throughout a uniformly cheesy basis, or they may be deposited in a partially softened, cheesy menstruum, when a mortar-like material results.

The tubercle becomes fibrous with the diminution in the number of its cells and the increase in the thickness of the reticulum, with the transformation of the latter into a homogeneous hyaline substance. The cornified, horn-like tubercle is one whose size is diminished from the shrinkage of its cells into glistening flakes, without an evident associated cheesy or fatty degeneration.

The intimate relation of scrofula to tuberculosis has been variously expressed from time to time in accordance with the amount and accuracy of the existing knowledge. At the outset the enlargement of the lymphatic glands, especially of the neck, characterized the scrofulous affection. As the enlargements of the glands were found to present intrinsic differences connected with differing clinical histories, only those glands were regarded as scrofulous which presented the cheesy appearances. With the recognition of the cheesy condition of tubercles the latter were identified with the scrofulous gland, from the cheesy condition common to both.

This identification of scrofula and tubercle prevailed till Virchow showed that cheesy material might have a different origin, and maintained that there were cheesy lymphatic glands without tubercle, as well as tuberculous lymphatic glands which might become cheesy. A distinction was thus drawn between scrofula and tuberculosis. The former term was applied to that condition of the individual which favored the retention and cheesy degeneration of inflammatory products, not only in the lymphatic glands, but elsewhere in the body. Tuberculosis, on the contrary, was characterized by the production of tubercles which were often accompanied by retained inflammatory products, both of which were prone to undergo cheesy degeneration.

The frequent association of well-defined tubercles with what were regarded as antecedent scrofulous disturbances also suggested an intimacy of relation between scrofula and tuberculosis. Virchow⁴⁹ had always maintained the possibility of regarding tuberculosis as a heteroplastic or metastatic scrofula. The occurrence of cases of tuberculosis without evidence of an antecedent scrofula prevented him from making a more absolute statement of the above relation.

⁴⁹ Die Krankhaften Geschwülste, 1864-65, ii. 629.

The views with regard to the connection between scrofula and tuberculosis have become essentially modified of late years as a result of the investigations concerning the etiology of tuberculosis.

In 1856, Buhl⁵⁰ first published his view, although he had for several years been impressed with the idea, that miliary tuberculosis was an infective disease resulting from the absorption of a specific virus. He based his theory upon the almost constant coexistence of one or several cheesy collections and miliary tubercles. The former were recognized as the remains of previous inflammatory processes, and the tubercles were looked upon as the immediate result of the absorption of this cheesy material. The individual thus infected himself. Buhl⁵¹ claimed that the simultaneous occurrence of tubercles and inflammatory products was the co-effect of the same cause, and that the acute miliary tuberculosis, as a localized process, was merely an inflammation with the development of tubercles. He restricted the term tuberculous inflammation, however, to those forms which necessarily and from the beginning, produced tubercles whose presence was limited to the tissue inflamed. The tuberculous inflammation was regarded as a primary condition, while the acute miliary tuberculosis was a secondary process resulting from infection.

⁵⁰ Lungenentzündung, Tuberkulose und Schwindsucht, 1872, iii.

⁵¹ Op. cit., 123.

The tuberculous inflammation of this author was largely characterized by those features which, with the exception of the constant presence of tubercles, were recognized by others as attributes of a scrofulous inflammation. At the same time, he objected to the latter term as a substitute, since its use would imply that no other cheesy product than that from a tuberculous inflammation would serve as the origin of tubercles. Buhl strictly maintained that the absorption of any cheesy material, whatsoever its source, might give rise to a general growth of tubercle in the body.

The views of this author were popularized mainly through the teachings of Niemeyer⁵² concerning pulmonary consumption. The latter adhered to Virchow's views relating to scrofulous inflammation, but maintained that most consumptives were in imminent danger of becoming tuberculous in accordance with the doctrines of Buhl.

⁵² Klinische Vorträge über die Lungenschwindsucht, 1867.

The theory of an infectious origin of tuberculosis, advanced from time to time by others, but most forcibly presented and maintained by Buhl, was first demonstrated by Villemin⁵³ in 1865. This observer showed that certain animals, especially rabbits and guinea-pigs, might be successfully inoculated, beneath the skin, with fragments of gray tubercle, cheesy products, sputum, and blood from cases of phthisis. The development of tubercles took place within three weeks after the inoculation, and became general within four weeks. He also demonstrated that rabbits became tuberculous when inoculated with bits of the tumors occurring in the pearly distemper of cattle.

⁵³ Etudes sur la Tuberculose, Paris, 1868, 528.

Villemin's observations have been repeatedly confirmed and extended; although subjected to the severest criticism and control, their results are so constant that the law of the inoculability of tubercle is almost universally regarded as fixed. Its value as a test is evident from the statement of Cohnheim,⁵⁴ who regards as tuberculous only that which produces tuberculosis when transferred to suitable animals. The transfer may be made in various ways. Chauveau and others were successful in producing an intestinal tuberculosis by the introduction of tuberculous material into the intestinal canal of animals, especially the Herbivora. Tappeiner⁵⁵ succeeded in producing pulmonary tuberculosis, with or without general tuberculosis, in dogs, by compelling them to breathe air in which were contained minute particles of sputa from tuberculous pulmonary cavities.

⁵⁴ Die Tuberkulose vom Standpunkte der Infections-Lehre, 1880, 13.

⁵⁵ Virchow's Archiv, 1878, lxxiv. 393.

The production of a tuberculosis of the iris, as well as of remote organs, by the inoculation of tuberculous material into the anterior chamber of the eye, was an ingenious method devised by Cohnheim and Salomonsen.⁵⁶ It permitted the direct observation of the several steps in the process of absorption of the inoculated material and development of the tubercles.

⁵⁶ Cohnheim's Vorlesungen über Allgemeine Pathologie, 2te Auflage, 1882, i. 707.

The objections to the various experiments above alluded to are based upon the assumption that the results of the inoculation are not tubercles, but inflammatory products resembling tubercles. It is further advocated that the inoculation of indifferent material, as bits of glass or hairs, as well as other foreign substances, will produce the so-called artificial tuberculosis, especially in rabbits and guinea-pigs. It is admitted that these animals readily become tuberculous when exposed to simple inflammatory irritants, the local action of which frequently results in the production of cheesy material. This termination is now regarded as due to faults in the method of experimentation, the animals not being thoroughly protected from the influence of the virus of tuberculosis.

The objection on the ground of structure loses its force in connection with the well known differences in the structure of miliary tubercles in the human body, already mentioned. The tubercles resulting from inoculation often resemble in structure the meningeal tubercles of the brain rather than the type presented by tubercles in lymphatic glands. The development of tubercles in the iris may take place without any permanent inflammatory reaction. The association of evidences of inflammation with the development of the tubercle is therefore unnecessary.

The experiments of Villemin have not only demonstrated the infectious nature of tuberculosis, but have also led to a more accurate knowledge of the relation between tuberculosis and its allied affections, scrofula and pearly distemper.

The anatomical characteristics of scrofula have obviously proved insufficient in determining the relation presented by this affection to tuberculosis. The tendency to cheesy degeneration of its inflammatory products was the feature of chief importance. Villemin showed that portions of a scrofulous (cheesy) gland when inoculated were followed by tuberculosis, and that the inoculation of cheesy material from non-tuberculous or non-scrofulous sources was not followed by this result. The assumption of Buhl, that the absorption of cheesy material, as such, was the cause of tuberculosis, was thus disproved. The frequency with which the inoculation of cheesy material, from what were regarded as scrofulous sources, was followed by tuberculosis, led to more exact studies concerning the anatomical peculiarities of scrofulous inflammation. Köster⁵⁷ called attention to the regularity of the occurrence of miliary tubercles in the fungous granulations of the inflamed joints of scrofulous and tuberculous individuals. Wagner⁵⁸ and Schüppel⁵⁹ discovered that scrofulous glands, in most if not in all instances, were tuberculous glands. The regularity of the presence of tubercles in scrofulous abscesses and ulcers of the skin and in scrofulous caries was shown by Friedländer.⁶⁰ This observer likewise called attention to the presence of agglomerated tubercles as the chief constituent of the new formation of lupus. These anatomical discoveries resulted in uniting more closely the affections scrofula and tuberculosis from the histological standpoint, and the union has become more firmly cemented from the etiological investigations.

⁵⁷ Virchow's Archiv, 1869, xlviii. 95.

⁵⁸ Loc. cit.

⁵⁹ Op. cit.

⁶⁰ Volksmann's klinische Vorträge, 1873, lxiv.

Schüller⁶¹ has shown that the introduction of finely divided material from a scrofulous joint—that is, from one containing tubercles—into the lungs of rabbits was followed by a tuberculosis of the tracheal wound, the lungs, and liver. Similar experiments with reference to the introduction of lupus-tissue produced results suggestive of tubercle, if not actually tuberculous.

⁶¹ Untersuchungen über die Enstehung und Ursachen der Skrophulösen und Tuberkulösen Gelenkleiden, 1880.

The intimacy of relation between tuberculosis and pearly distemper is a necessary result of Villemin's⁶² experiment, in which the rabbit became tuberculous after inoculation with fragments of the pearly tumor. Gerlach,⁶³ and especially Schüppel,⁶⁴ showed that the structure of the nodules of the pearly distemper is the same as that of the tubercles of man, and that the two diseases are identical from the histological point of view.

⁶² Op. cit., 537.

⁶³ Virchow's Archiv, 1870, li. 290.

⁶⁴ Ibid., 1872, lvi. 38.

From the anatomical identification and the etiological connection, as shown by Villemin, Gerlach, and Aufrecht, the pearly distemper became designated as a bovine tuberculosis.

The experiments of Villemin were further productive in leading to the discovery by Koch of the bacillus tuberculosis. It was early obvious that certain cheesy material and gray tubercles possessed the infectious qualities, and Villemin⁶⁵ maintained that the immediate cause of the latter was a germ introduced from without, which propagated and perpetuated itself in man and certain animals. This view acquired prominence through the investigations of Klebs, who in 1877 claimed to have isolated the micrococci which produced tubercles when injected into animals. Three years later Schüller⁶⁶ confirmed the statements of Klebs, and asserted that he had been enabled to obtain infective micrococci by cultivation from miliary tubercles, scrofulous glands and joints, and from the tissue of lupus. Aufrecht⁶⁷ found micrococci, single and in chains, and short glistening rods, within tubercles resulting from inoculation with material from pearly tumors. The same organisms were found in tubercles produced by the inoculation of tubercles from man, and he regarded these rod-shaped bodies as the specific element productive of miliary tuberculosis.

⁶⁵ Op. cit., 620.

⁶⁶ Op. cit., 55.

⁶⁷ Pathologische Mittheilungen, 1881, p. 43.

The isolation of the virus of tubercle was thus regarded as an open question till the announcement by Koch⁶⁸ of the constant presence of a hitherto unknown, characteristic, well defined organism in all tuberculous affections, which, when isolated and introduced into animals, produced tuberculosis, the resulting tubercles likewise containing the organism.

⁶⁸ Berliner klinische Wochenschrift, 1882, p. 15.

The latter, the bacillus tuberculosis, was to be seen in preparations methodically treated and carefully stained with aniline colors, by all of which, excepting the browns, the bacillus was tinged. It was found in miliary tubercles of the lung, cerebral and intestinal tubercle, cheesy bronchitis and pneumonia, phthisical sputa, scrofulous glands, and fungous inflammation of the joints. It was also seen in the nodules of pearly distemper and in the cheesy masses from the lungs of cattle. It was furthermore met with in the cheesy lymphatic glands of swine, in the tubercular nodules of a fowl, and in the tubercles of guinea-pigs, rabbits, and monkeys. The bacilli were likewise found in the tubercles resulting from the inoculation of animals with tubercular virus from its various sources.

The microphytes were described as very slender rods, varying in length from one-fourth the diameter of a red blood-corpuscle to its entire diameter, and spores were occasionally seen within the rods. In shape and size they resembled the bacilli of leprosy, but the latter were narrower and pointed at the ends. They were found in greatest abundance when the tuberculous process was recent and rapidly advancing, and were present within, as well as between, cells. The younger giant-cells contained them in larger numbers than the older forms. They were present at the periphery of cheesy nodules rather than at the centre.

The bacilli were cultivated through successive generations and required a temperature of between 30° C. and 41° C. (86° F.-105.8° F.) for their development, one of 37° C. or 38° C. (98.6° F. or 100.4° F.) being the most favorable. The crop first became apparent on the tenth day after sowing, and the growth extended through a period of three to four weeks, forming a compact scale. The cultivated bacilli, even propagated through several generations, when inoculated, produced the same positive results as follow the inoculation of fragments of tuberculous material, although animals might be used which are not easily infected with tuberculosis.

Koch's publication was immediately followed by a statement from Baumgarten⁶⁹ of his discovery of rod-like bacteria in the tubercles of rabbits resulting from the inoculation with pearly masses, and in the pleural and pericardial tubercles of man. They were made evident by treating the sections for microscopic examination with very dilute solutions of soda or potash.

⁶⁹ Centralblatt für die med. Wissenschaften, 1882, xv. 257.

The discoveries of Koch thus show that the production of tuberculosis is dependent upon the presence of distinctive bacilli, and that these bacilli are present not only in miliary tubercles, but in scrofulous glands and joints, in cheesy inflammation of the lungs, and in the pearly distemper of animals. The identification of tuberculosis with the pearly distemper and certain scrofulous affections is thus established from the etiological as well as the histological point of view.

As the bacilli are to be regarded as the virus of tuberculosis, so their introduction into the human body is necessary for the production of this disease in man. It is obvious, however, that other factors than the virus are necessary, for not every one exposed to the reception of tubercular bacilli becomes tuberculous. It may well be that scrofula is still to be regarded as that condition of the solids and liquids of the body which offers favorable opportunities for the retention and growth of the bacilli, and thus for the production of tuberculosis. Formad⁷⁰ claims that he has discovered structural peculiarities of tissue as a cause for the scrofulous habit, which he regards as synonymous with a predisposition to tuberculosis. These peculiarities are manifested by a narrowness of the lymph-spaces and their partial obliteration by cellular elements. He also maintains that these features are not only of congenital origin, but may be acquired through malnutrition and confinement.

⁷⁰ Studies from the Pathological Lab. of the Univ. of Penna., reprint, 1882, xi. 3.

The occurrence of a local, circumscribed tuberculosis in extreme old age, without antecedent or other concurrent evidence of scrofulous disturbances, suggests that favorable opportunities for the development of the tubercular bacillus may arise in advancing years. In like manner, the frequent termination in phthisis of cases of diabetes suggests the likelihood of tuberculous inflammation arising in the absence of any evidence of previous scrofulous or tuberculous disease. The scrofulous condition or constitution, as indicated by vulnerable tissues, with a protracted course of inflammations, and a persistence of their products, with a tendency to cheesy degeneration, may still exist without a sign of tuberculosis. Those who claim that scrofula and tuberculosis are identical must, in the light of Koch's discovery, demonstrate the presence of the bacillus in all scrofulous inflammations, and deny the existence of scrofula apart from indisputable manifestations of the activity of the bacilli of tuberculosis. It may be that such evidence will be presented; until it is collected scrofula and tuberculosis are to be regarded as distinct though often coexistent. The scrofulous person is frequently tuberculous, the tuberculous person is usually scrofulous; the non-scrofulous person, however, may die of tuberculosis, while the individual may be scrofulous without containing tubercle.

The actual inheritance of tuberculosis is very unlikely, although this disease is frequently found in successive generations of a single family. The various members of the family are rather to be regarded as furnishing a suitable soil for the growth of the tubercular bacillus, and their exposure to its seed is favored by the existence of tuberculosis in one or more members of the household. The scrofulous condition is still to be regarded as hereditary as well as acquired, and the scrofulous remain as the class to be especially protected from the reception and effects of the bacilli of tuberculosis.

It is obviously a matter of importance to determine in any given case of phthisis whether bacilli are present or absent. A ready means of ascertaining this fact is offered by the examination of the sputum in cases of pulmonary phthisis, the feces in intestinal phthisis, the urine in renal phthisis, and the aspirated pus in cases of supposed tuberculosis of the joints. Koch has found in examining the sputa from numerous cases of phthisis that the bacilli were present in one-half the number, and that they were absent from the sputa of individuals who were not phthisical. Balmer and Fraentzel⁷¹ have found bacilli in the sputum from one hundred and twenty cases of phthisis, and concluded that the progress of a case of pulmonary tuberculosis might be readily determined from the number and degree of development of the typical bacilli present in the sputum. The more numerous and well-developed bacilli, with distinct and constant spores, were found in the graver cases, which advanced more rapidly. The sputum of the protracted cases contained few, small, and thin bacilli with scanty spores. The presence of fever was associated with numerous bacilli, while its absence was noted in those cases where but few were present.

⁷¹ Berliner klinische Wochenschrift, 1882, xlv. 679.

The bacilli are readily detected by means of the staining method devised by Koch. Various modifications have been presented from time to time, of which that of Ehrlich⁷² has proved the most satisfactory. The essential features are to obtain a dry, thin layer of a selected portion of the suspected sputum, which is then to be deeply stained with fuchsin or methyl-violet; the excess of color is to be removed with nitric acid, and the preparation is then ready for examination with the microscope. A power of four or five hundred diameters is sufficient for the recognition, and the object should be illuminated with a flood of light through a large diaphragm or an achromatic condenser. The bacillus retains the color notwithstanding its exposure to the acid, and the violet colors are more strongly presented if the preparation is tinted yellow after the action of the acid. If the bacilli are stained red with fuchsin, the background should be made blue. It is important that the reagents should be freshly prepared and filtered, that other bacteria may not obscure the picture, and that all the apparatus employed should be thoroughly clean.

⁷² Allg. med. Centr. Zeitung, 1882, xxxvii. 458.

A fragment of thick, opaque sputum is to be taken in forceps, placed on a cover-glass, and spread into a thin layer by means of a second cover-glass. The prepared slide is then to be passed slowly through an alcoholic flame, or that of a Bunsen burner, till the layer of sputum is dried. A saturated alcoholic solution of methyl-violet or fuchsin is made and filtered, and added, drop by drop, to a filtered, saturated solution of aniline oil shaken in water. The color is to be added with stirring till an opalescent film forms on the surface of the mixture. The slide containing the dried sputum is to be placed in or on this staining fluid, and allowed to remain for half an hour or less, the application of warmth hastening the process, when it is removed, and the specimen is decolorized in a solution of one part of nitric acid and two parts of water. The preparation is then washed in water, and may be examined directly in water, glycerin, or, after dehydration in alcohol, in oil of cloves. The tinted bacilli are made more prominent by a secondary staining, for a minute or two, of the red (fuchsin) preparation in a concentrated solution of methyl-blue, the violet preparation being secondarily stained in a like solution of aniline-brown. If the preparation is to be permanently preserved, it should be dehydrated in strong alcohol after washing with water, and it may then be treated with oil of cloves and mounted in Canada balsam.

After the observer has become thoroughly familiar with the tubercle bacilli by means of the method of Ehrlich, much time may be saved by following that of Baumgarten.⁷³ The cover-glass bearing the dried sputum is placed in a very dilute solution of caustic potash (two drops of a 33 per cent. solution in a watch-glass of distilled water) till the layer of sputum becomes transparent. The cover is then placed on a slide moistened with a drop of water, tapped slightly, and examined with the microscope. The bacilli are readily seen, and may be differentiated from other varieties of bacteria, if necessary, by again drying the object and examining it in a drop of a dilute watery solution of aniline-violet or of other preparations of aniline used for staining nuclei. The tubercle bacilli remain unstained, while putrefactive bacteria are tinted.

⁷³ Centralblatt für die med. Wissenschaften, 1882, xxv. 433.

The tubercular products of the invasion of the body by the bacillus tuberculosis are regarded as primary or secondary, according as they are present at that part of the body which directly receives the organisms or as they are dependent upon the transfer of the latter to parts remote from the region of their admission and immediate effects. This differing relation is also expressed by the terms local and general tuberculosis. In the former the bacilli excite the growth of tubercle only at a given part of the body. Their apparent effects may be wholly limited to this region, and it not rarely happens that the same is quite distant from the channels through which the bacilli are admitted. A general tuberculosis occurs when the latter are disseminated over the body, and their effects, especially the production of numerous tubercles, are found at various parts. The dissemination may take place at the time of entrance, or, as is more commonly the case, apparently occurs at some subsequent period, the immediate disturbances being localized at a given portion of the body. The necessary conditions being here offered for the propagation of the bacilli, their sudden distribution in great numbers is afterward permitted when favorable opportunities arise for their absorption. Such conditions are present when the local tubercular growths extend into lymphatics or blood-vessels. The frequency with which scrofulous glands are tuberculous—that is, contain miliary tubercles—is already fully recognized, and a tuberculosis of the lymphatic glands is essentially regional. These glands become affected in consequence of disturbances, the local effects of which may have wholly disappeared, in the region from which they receive their lymph. The cervical glands become permanently enlarged, perhaps tuberculous, in connection with persistent or recurrent inflammatory processes in the tonsils and pharynx, the bronchial glands from similar bronchial or pulmonary affections, and the mesenteric glands from like intestinal disturbances. In such instances, the direct reception of the bacilli into the lymph-current is assumed rather than demonstrated from a knowledge of the possibilities of absorption and an appreciation of the conditions in the glands.

That an actual growth of tubercles from the wall of the intestinal lymphatics may take place has long been known, and Ponfick has recently discovered that tubercles may be found growing from the wall of the thoracic duct. The possibility of the direct admission into the lymph-current of the infective element in tuberculosis is thus apparent, and its indirect entrance into the blood-current is equally obvious. That the bacillus of tubercle may be directly received into the blood-current is likewise evident from the observations of Weigert, who found tubercles growing from the walls of the pulmonary blood-vessels, venous as well as arterial. This discovery of a tuberculosis of the blood-vessels was confirmed by Klebs, who had found a tuberculosis of the azygos veins. The occurrence of multiple miliary tubercles of the pulmonary veins, especially near the place of entrance of smaller branches, has been asserted by Mügge,⁷⁴ although appearances similar to those described by him may be met with, due simply to the agglomeration of white blood-corpuscles and their necrosis. Such a condition simulates very closely the miliary tubercle, but is usually analogous to the appearances figured by Virchow,⁷⁵ and described by him as one of the phenomena of coagulation. In his observation the white bodies were adherent to the red clots, and were with them drawn from the pulmonary artery.

⁷⁴ Virchow's Archiv, 1879, lxxvi. 243.

⁷⁵ Die Cellular Pathologie, 4te Auflage, 1871, 184.

With the admission into the body, and the colonization of the tubercular bacilli, their effects may either be progressive until the death of the individual is occasioned, or, with the cessation of the growth of the bacilli or a possible modification of their noxious properties, recovery may ensue. The history of scrofulous glands, as well as that of circumscribed pulmonary inflammation in scrofulous persons, both presumably of a tuberculous nature, show that the effects of an invasion of the parasites may be overcome.

The regions of the body which are usually the seat of a primary tuberculosis are unquestionably the respiratory and intestinal tracts. With regard to the first of these regions, the one most frequently affected, there can be no doubt that in most instances the inhaled air carries the bacilli or their spores, or both. Their constant presence in the sputum of the frequent cases of tuberculous phthisis suggests a ready means for their escape into the atmosphere. The well recognized infective qualities of the sputum, as demonstrated by the various experiments before the bacillus was discovered, demand the thorough disinfection of phthisical sputa, since these are in all probability the chief source of the dissemination of the disease.

The tuberculosis of the intestine in like manner is to be regarded in the main as the result of an absorption from its surface of the specific agent. An obvious direct means of the approach of the bacilli is offered in the sputum, which, when swallowed, is likely to retain its virulent properties. The frequent coexistence of chronic pulmonary and intestinal tuberculosis is thus most readily explained. To what extent the presence of the bacilli in the pearly distemper of cattle and in the tuberculosis of other edible domesticated animals, as fowls and swine, may lead to an infection of the intestinal wall, still remains an unsolved problem. It is not yet determined at what temperatures the bacilli are destroyed, although their growth takes place only between 30° C. (86° F.) and 41° C. (105.8° F.). The inoculation of pearly masses produces tuberculosis in certain animals, yet the effect of cooking in destroying the bacilli and their spores is likely to prove of great importance. Aufrecht's⁷⁶ attempts at inoculating rabbits with cooked pearly masses proved unsuccessful. Schottelius⁷⁷ publishes an interesting series of observations relating to the prolonged use of meat from cattle affected with the pearly distemper, and shows that after a period of years no disease of the nature of tuberculosis occurred among the one hundred and thirty individuals included in the families concerned. Whatever may be the value of this negative testimony, there is, as yet, no evidence on the other side which satisfactorily determines the point in question—viz. that the flesh of animals affected with pearly distemper produces tuberculosis in the human consumer.

⁷⁶ Op. cit., 51.

⁷⁷ Virchow's Archiv, 1883, xci. 129.

The milk from cows thus diseased has likewise been regarded with suspicion, and the frequency of intestinal tuberculosis among children has been attributed to this source. Although the theoretical possibility of the escape of the bacilli into the milk of cows affected with pearly distemper is obvious, their presence in such milk is first to be demonstrated under conditions which necessitate their origin from the animal. If boiling the infective material for three minutes destroys its virulence, as claimed by Aufrecht, a ready means is offered of destroying the tubercle bacilli which may be present, not only in the milk from animals affected with pearly distemper, but in all milk which has been exposed for a certain time to an atmosphere which may contain the bacilli of tuberculosis. In the light of our present knowledge extreme hygienic precautions are only demanded in those cases where such a congenital or acquired basis (constitution) is present as facilitates the development of tuberculosis.

Morbid Growths.

In a system of practical medicine it is obviously important to include under the head of Morbid Growths not only what is spoken of by the surgeon as a tumor, but also those new formations of tissue which, in virtue of their nature, seat, manner of growth, and retrograde changes, produce an important series of disturbances in the physiological processes of the individual. The surgeon deals essentially with the swelling, which, producing irregularities in the outline of the accessible surfaces of the body, is regarded as an excrescence or outgrowth. It is important for him to realize the nature of this swelling, that he may follow a different treatment for the abscess, the wen, the watery accumulation, or the fleshy mass. The last is the tumor in the limited sense; it is the growth which, though called morbid, becomes so only in consequence of its presence being associated with symptoms whose existence and persistence interfere with the well-being of the possessor.

The physician, on the contrary, is more concerned with the tumor as a growth than as a swelling. The latter element in deeply-seated portions of the body may not be brought to his attention. The growth takes place in such a manner as to be productive of certain symptoms more or less serious, among which swelling is least obvious. The morbid growth to him becomes prominent as it displaces or replaces normal tissues by those newly formed, which may or may not be normal to the part in which the growth is situated. His tumor is therefore a morbid growth, a new formation, a neoplasm or pseudoplasm, rather than a swelling, a bunch, or an excrescence.

In a consideration of the general pathology of morbid growths the first question which suggests itself relates to the method of origin of the tumor. The tendency of the present seeks for a local cause, and the most recent theory, that of Cohnheim, demands an accumulation of dormant embryonal cells as such a cause. Cohnheim supports this view by the experiments of Zahn and Leopold, which show that foetal cartilage transplanted into the tissues of a mature animal may grow so rapidly as to present the characteristics of a cartilaginous tumor, while tissues transferred from the animal after birth do not increase in size, but are usually absorbed.

As the active elements of the growth are cells, and all cells admissibly arise from pre-existing cells, it follows that the primitive cells of a tumor are derived from those resulting from the segmentation of the ovum or are introduced from without. Numerous experiments have been made with a view to the inoculation of tumors, the transplantation of living fragments of the latter to the living tissues of a healthy individual, for the sake of producing a tumor, but hitherto almost invariably without success. The alternative remains that the embryonal cells are those whose derivatives are present in, and form the essential element of, the morbid growth. All tumors may thus be said to have an embryonal origin. As the segmentation of the ovum eventually results in the production of normal tissues and groups of tissues whose structure and function are wholly different, so the possibility of the production of abnormal groupings of tissue with corresponding irregular manifestations of function is obvious.

The cells of the part from which a tumor arises may be regarded as indifferent, those whose limitations of growth, like the early embryonal cells, are only determined by the changes they undergo, or their limits of growth may be already defined in kind, and their like be produced in the formation of the tumor. The origin of a tumor thus presupposes the existence of such indifferent cells, or the presence of those whose limit of transformation has already been reached. The leucocytes of the body, whether found as white blood-corpuscles or lymph-corpuscles, or as the wandering cells of connective tissue, are, as Virchow has indicated, such indifferent cells. Always present and apparently transitory, what they are to become can only be determined from their condition and surroundings at the time of observation. Although their actual transformation into the various cells of a more permanent type is merely a matter of inference in the growth of tumors, the evidence presented by Ziegler⁷⁸ leads directly to the conclusion that their presence is necessary to the new formation of tissues whose growth is the result of an inflammatory process. These tissues may occur under such restrictions as permit them to be classified as tumors, and the granulomata, or tumors whose tissue resembles that of the granulations upon the surface of a wound, represent a well defined group in structure as well as method of origin.

⁷⁸ Op. cit., 150.

The production of the cells of a tumor from indifferent cells is at present an assumption, based upon the frequent presence of the latter within tumors and in their vicinity; and the obvious objection arises that even if the presence of these cells is admitted as indispensable, it by no means follows that they are directly transformed into the more characteristic cells of the tumor. That they may serve for the nourishment of the amoeboid cells of certain tumors is suggested by the existence of both in morbid growths, and the well-known property of amoeboid corpuscles to take in formed material, even cells, from without.

The origin of tumors from cells whose limits of growth are already defined is rendered probable from the absence, entire or in great part, of indifferent cells from certain tumors, and the direct continuity of the latter with a similar normal tissue of the body. Various tumors show such an intimate relation, and there is no sharply defined border-line between the normal tissue and that which represents the tumor. The occasional presence of islets of well characterized tissue at points more or less remote from the normal position of such tissue at the time of their discovery suggests a feasible source for an eventual tumor. Virchow long ago called attention to isolated nodules of cartilage within bones in the vicinity of epiphyseal cartilages, probably detached from the latter, which might serve as the origin of a cartilaginous tumor in this region. This inclusion of tissue is also suggested by the frequency of certain tumors in certain regions where the developmental conditions are favorable. Lücke⁷⁹ mentions the frequency of dermoid cysts near the median line of the head, the vicinity of the eye, and the side of the neck. Such regions are those where fissures exist during foetal life, with normal involutions of the outer germinal layer; which involutions may become irregular, and eventually included or shut in, as the fissures become closed. A similar explanation is offered for the frequent occurrence of cartilaginous tumors at the angle of the jaw, it being thought probable that bits of embryonal cartilage, during the formation of the ear, become included in the salivary glands.

⁷⁹ Volkmann's Sammlung klinischer Vorträge, xcvii. 819.

In like manner, Cohnheim explains the frequent occurrence of certain epithelial tumors at the orifices of the body—the cervix uteri and the vicinity of the tracheal bifurcation—not through the exposure of these parts to injury, but because they are regions in which embryonal irregularities of development are likely to arise.

That congenital, local peculiarities are an important element in the origin of tumors has already been strongly advocated by Virchow. Not only are children born with tumors, but instances of growths eventually arising from birth-marks, and the occurrence of certain tumors in the same locality in successive generations of the same family, are sufficiently familiar.

Although certain tumors are admitted to be due to congenital peculiarities of tissue, and even to represent atypical growths from embryonal tissue, the theory of such an embryonal origin for all tumors seems unnecessary. The resemblance in symptoms as well as in appearance, and even in structure, of certain tumors to inflammatory products, and their frequent association with these, has led to the suggestion of an irritant as an exciting cause for the tumor, even in the absence of local peculiarities of tissue. It is obvious that were the embryonal theory of origin, as extended by Cohnheim, universally applicable, the growth demands something more than a focus of embryonal cells. An immediate cause for their growth after a dormant period, extending even into old age, is required. Cohnheim finds such in a sufficient supply of blood. He attributes the development or rapid growth of the tumor to this feature, and supports his view by the usual appearance of exostoses when the skeleton is at its period of most vigorous growth, and of dermoid cysts at a time when the formation of the beard indicates active developmental conditions in the outer germinal layer.

The growth of ovarian cystomata at and after puberty, and of these and mammary tumors during pregnancy, are also explained on the ground of a more abundant supply of blood at such periods. He and others find in physiological conditions a source for the abundant blood-supply—that is, the efficient nutrition for the growth of a tumor. The necessity of sufficient nutrition in the development of tumors is universally admitted, and its source may be looked for in pathological as well as physiological conditions.

The existence of an irritant of some sort often seems probable, and, although its absence is more frequently determined than its presence, it is obvious that when present it may be overlooked. Although traumatic irritants of considerable mechanical severity exist in but a small percentage of tumors, their occasional influence in the production of morbid growths is not to be denied. Their action may be explained as producing a congestion or as enfeebling the opposition of physiological tissues to pathological growths. The importance of an irritant as the exciting cause, however its action may take place, is supported not only by the sequence of injuries and tumors, but also by the frequent occurrence of tumors in parts exposed to injury and irritation. Such exposure may result from position, structure, or function. The orifices and prominences of the body, the retained testis in the inguinal canal, are notoriously liable seats of tumors. Soft, friable, and slightly resistant structures, like mucous membranes, are not only the frequent place of origin of tumors, but the most exposed parts of such structures are oftenest affected. The exposure resulting from function is manifest by the relation presented by the periods of greatest functional activity of the growth of tumors in such organs as the mammary gland, uterus, and ovaries.

The importance of an irritant is still further suggested by the association of tumors with inflammation. The growth of tubercles and cancer from serous membranes is frequently accompanied by an acute inflammation of the latter; fibrous tumors and chronic interstitial inflammations often coexist, while elephantiasis is usually preceded by recurrent, erysipelatous inflammation of the skin.

The recent discovery of infective organisms as an exciting cause for many of the members of an entire group of tumors, the granulomata, has resulted in making prominent the etiological rather than the structural features of the tumors concerned.

Local peculiarities of tissue, whether congenital or acquired, are thus regarded as representing the beginnings of the growth. With the multiplication of the cells their transformation may take place or a change in their grouping may arise. The essential condition in the production of the morbid growth is that the formation of the cells should take place at an abnormal time or place and should progress in a normal or abnormal manner.

The growth takes place with greater or less rapidity in one or another direction according to the nature of the tumor and its seat. The more closely the tumor resembles the normal structures of the body, the slower is its growth; the more it differs in composition, the more rapid is its progress. This difference may arise from a predominance of cells over intercellular substance, as in the case of the sarcoma, or it may result from an atypical combination of tissues, as seen in the development of epithelium and connective tissue in cancer.

The seat of the tumor is of importance mainly on account of the vascular supply of a part and the more spongy or yielding nature of certain regions. That the more abundant the nutrition of certain regions of the body, the more favorable the opportunities for growth, may be admitted without question. The spongy nature of tissues implies a predominance of cavities over solid constituents. These cavities are lined by surfaces which represent, on the one hand, the walls of lymph-spaces, on the other the free surfaces of the body exposed to the air, as the mucous or cutaneous surfaces and the pulmonary surface. The rapidity of growth in the direction of the least resistance is amply shown in the projection of tumors above the surface of serous membranes and the frequent presence of fungoid excrescences in various parts of the body.

The growth of tumors extends in all directions, but a distinction has long been drawn between the concentric or interstitial manner of growth and the excentric or infiltrating form. This distinction is based upon the presence of a sharply defined limitation of pathological and normal tissues or upon the absence of such a limitation. Such a distinction is merely of relative importance, as certain tumors may grow in both ways. This is best observed in those bulging superficial tumors whose base is irregularly extended into the continuous healthy tissues.

The concentric variety of growth includes those tumors which have commonly been described as encapsulated, and which are capable of ready enucleation from their surroundings in virtue of a thin layer of loose connective tissue lying between the tumor and the contiguous tissue. Such a capsule represents the matrix, the pia mater, in which lie the blood-vessels going to and coming from the tumor, and is often nothing else than the distended and hyperplastic fibrous tissue remaining after the absorption of the muscular fibres or gland-cells from the tissues surrounding the morbid growth.

The excentric, peripheral, or infiltrating extension of the tumor takes place when the surrounding parts are invaded by the active elements of which the tumor is composed. The amoeboid property of the cells of certain tumors is well known, and the possibility is admissible that the indifferent cells of the body, so often accumulated at the periphery of the growth, become impregnated with a formative function by the constituents of the tumor. Such amoeboid and wandering cells represent a means through which the growth of the tumor may become extended in its vicinity as well as in more remote parts of the body.

The extension in the vicinity may be continuous or the reverse, the latter through the formation of secondary nodules, which may eventually become fused with the primary mass. The continuous growth takes place, as has been more particularly shown by Köster, along the lymph-channels surrounding the tumor, which may become filled, distended, and eventually obliterated by projections from the neoplasm. Both methods of peripheral growth, by secondary nodules and continuous extension, represent an infection of the surrounding tissues, especially if it be admitted that the cells through which the increase is accomplished are direct descendants of the pre-existing cells of the part. Not only does the extension take place through the lymphatic vessels about the tumor, but blood-spaces as well as lymph-spaces may be invaded. Thrombi are then found whose structure is frequently that of the tumor, and whose connection with the same is direct through the perforated wall of the vessel. These features in the growth of tumors lead directly to the consideration of the means by which multiple tumors appear in remote parts of the body after a single tumor has appeared in a given locality, and after the removal of such a primitive growth.

The distinction between primary and secondary tumors is now so obvious that one is inclined to forget that the presence of numerous tumors at various parts of the body was at one time regarded as evidence of the constitutional or dyscrasic nature of the morbid growth. Such a multiplicity seemed to indicate that the blood was charged with the constituents of the tumor, which were deposited at various parts of the body.

Although certain multiple tumors may be present in different localities without an apparent relation between an antecedent and a subsequent growth, such tumors are usually limited to certain systems of the body. Multiple bony tumors are found growing from bones, fibrous and warty tumors from the skin, and fibro-myomata from the uterus. Cohnheim's theory of the embryonal origin of tumors may seem applicable in such cases, but the frequent association of the osteomata with chronic inflammatory conditions, of cutaneous warts and fibrous tumors with local irritative processes, makes such a hypothesis unnecessary.

Those tumors whose multiplicity is of the greatest clinical importance are the rapidly growing forms terminating fatally. Such are those which reappear in the scar after the removal of a cancer, or in the adjoining chain of lymphatic glands or at remote parts of the body. The most satisfactory explanation of their presence, and of the generalization, recurrence, or metastasis of tumors, is derived from what has already been stated with reference to the manner of the growth of the latter.

It is well known from experiments on animals that various living, normal tissues when transplanted to remote parts of the same individual or to other individuals may continue to grow. Cohnheim claims, as has been previously stated, that a distinction is to be drawn in this respect between the tissues of the adult and the foetus, where the genesis of tumors is concerned. This observer, in connection with Maas,⁸⁰ has found that the transplanted material (periosteum), although growing for a while, disappears at the end of five weeks, and it is asserted that fragments of tumors, when transferred, suffer a similar fate. Wile,⁸¹ on the contrary, who has experimented with reference to the fate of transplanted tissues and portions of tumors, reports that one hundred days after the transfer of periosteum the lung was found to contain several centres of ossification. He regards the latter as proceeding from the fragments of periosteum introduced into the jugular vein, and his results thus widely differ from those of Cohnheim.

⁸⁰ Virchow's Archiv, 1877, lxx. 161.

⁸¹ The Pathogenesis of Secondary Tumors, reprint from Philadelphia Med. Times, July, Aug., and Sept., 1882.

Notwithstanding the numerous experiments which have been made in various parts of the world to excite the growth of transplanted bits from tumors, most of them have terminated unsuccessfully. Although a temporary growth of fragments of tumors has taken place after transplantation, their eventual disappearance has usually occurred. Cohnheim lays stress upon this fact in connection with his theory of the origin of tumors. He considers that the fragments of tissue and tumors disappear in consequence of the inability of the foreign particles to withstand the metamorphosis of physiological tissues. If this opposition is neutralized, the existing germs of tumors become capable of development. Wile, however, found that eight weeks after the introduction of a bit of cancer into the lung of an animal the fragment had increased nearly twice in size. He also refers to the positive experiments of Newinsky,⁸² who transplanted a bit of cancer from a dog to the subcutaneous tissue of another, young dog, and found, after five months, not only an ulcerating cutaneous cancer at the place of inoculation, but also a metastatic nodule of the size of a hazel-nut in an axillary lymphatic gland.

⁸² Allgem. medicinische Central-Zeitung, 1876, lxxi. 875.

For the present consideration it may be borne in mind that fragments of normal (foetal) tissues, as shown by the experiments of Zahn and Leopold, when introduced into the organs of animals, may become enlarged. It is also certain that bits of tumors, after their introduction into the tissues and organs of animals, have become increased in size. What their eventual fate might have been does not appear; and herein lies the weak point of the experiments with reference to the production of secondary tumors. For such experiments to be regarded as crucial it is necessary that a large number of previously healthy animals, after inoculation with fragments of morbid growths, should present in various parts of the body well characterized tumors whose structure should be like that of the particles introduced.

The experiments above referred to are of value in confirming the views concerning the generalization of tumors which have been generally admitted since Virchow's discoveries with regard to the phenomena of embolism.

Tumors are said to become generalized when they appear not only in various systems of the body, but in various organs and tissues. They are found usually in considerable numbers, and with such differences in size, shape, and appearance as to indicate different ages. Such tumors are regarded as arising directly or indirectly from a common source. This source is called the primitive or primary tumor, and its derivatives the secondary tumors. The latter are usually considered as the direct descendants of the former, although their relation may be that of several successive generations.

The primitive tumor in its growth may extend into lymphatics and blood-vessels, as has already been suggested. Such an extension may be so little obvious when the tumor is removed by the surgeon that all diseased tissues are apparently separated from the body. A recurrence of the tumor is said to take place when the growth returns in the cicatrix, frequently in a multiple form. The explanation of such a recurrence is based upon the probable presence, at the time of the operation, of fragments of the tumor within the tissues forming the base and edges of the wound. During and after the healing of the wound their growth is supposed to continue till they become apparent as small tumors. The progress of these recurrent tumors is at times extremely rapid, and they may attain a considerable size in the course of a few weeks. Such nodules are secondary in point of time, although they were actually a part of the primary growth.

Secondary nodules in descent as well as time are those which appear at distant parts, often after the discovery of the primary tumor. Such nodules are regarded as resulting from the transfer of particles of various size from the primitive growth, either through the lymph-vessels or blood-vessels. If the invasion of the body takes place through the former, the fragments may be floated along to the nearest lymphatic gland, where it remains when too large to pass through. If it retains the capacity of growth or of stimulating a like growth, there results a more or less complete transformation of the gland into a morbid tissue like that from which the fragments came. Adjoining lymph-glands may become infected from the first, until eventually an entire series becomes more or less completely transformed into morbid growths. A like invasion of the lymphatic glands may take place through a continuous extension along the lymph-vessels; and it is not rare to find the sub-pleural or sub-peritoneal lymphatics as an elevated meshwork in consequence of the neoplastic growth within them. Such a method of extension may take place when a cancer of the stomach or liver is associated with a cancer of the pleura, the intervening lymphatics of the diaphragm offering a direct and continuous communication.

With the outcropping of a tumor upon a serous surface the possibility of the detachment of particles is at hand. These may become transplanted to the opposed serous surface or may be transferred to the most dependent parts, and there serve as seed for subsequent growth.

The probability of the embolic nature of many secondary tumors was early suggested in the history of embolism. Rapidly growing tumors were known to be capable of perforating the walls of adjacent blood-vessels, especially veins, and to continue growing along the course of such vessels. The possibility of the detachment of portions of these tumors and their transfer along the course of the circulation was an inevitable inference from the results of experimentation with foreign bodies. Cancerous emboli were thus recognized as a possible variety, and their distribution was subject to the same laws as those governing emboli otherwise constituted. Multiple nodules were frequently found in the lungs in connection with tumors growing into the inferior vena cava, while multiple nodules in the liver were usually associated with tumors of the gastro-intestinal canal or other regions whose vessels formed a part of the portal circulation. The readiness with which portions may be detached after death from the soft masses projecting into the interior of veins suggests the ease with which particles may be separated during life. The experiments already referred to show that isolated fragments of tissue serving as emboli may grow in the place of their reception, and it is presumable that the resulting growth takes place under the same conditions as those prevailing at the place from which the embolus started. The question whether the secondary tumor arises from the reproduction of elements transferred from the primitive disease, or whether these excite a characteristic, specific growth of the cells in the place of their retention, may still be regarded as open. The experiments favor the former view, and they alone are capable of satisfactorily determining the point in question.

The secondary nodules, whatever may be their method of origin, present the peculiarities of the primitive growth. If the cells of the latter are pigmented, those of the former show the same peculiarity. If the structure of the primitive tumor contains bone, cartilage, or squamous epithelium, the secondary growths show like characters, though they may be present in the heart or other organs where such tissues are not present as normal constituents. So constant and characteristic is this feature that the structure of the tumor is usually as well displayed in the examination of the secondary as of the primitive nodule. Indeed, the structural peculiarities of the growth may be more characteristically shown in the former in those instances where the primitive tumor has undergone degenerative changes obscuring its histological features.

The tissues of the tumor are subject to the various changes which take place in the normal tissues of the body. Their growth is attended with a multiplication of cells and a formation of intercellular substance. Tumors whose growth is the most rapid are those whose blood-vessels are the most numerous and whose relation to the cells is most intimate. The slower the advance of the tumor, the more permanent is it likely to become, while the more rapid the progress, the more transitory are its elements. The growth may continue, and yet the actual size of the tumor may diminish through the absorption of its degenerated parts. The cells of the neoplasm may undergo fatty degeneration, or they may become cornified. They may undergo the mucous metamorphosis or the amyloid and colloid degenerations. They may take up pigment or they may produce the same. The intercellular substance varies in its character as does that of normal tissues. It may be slimy, homogeneous, or fibrillated. It may contain mucin, chondrin, or gelatin, and may be infiltrated with calcareous salts. Limited necroses with characteristic cheesy appearances are of frequent occurrence.

Tumors may become the seat of inflammatory processes, indicated by suppuration and fever, which may result in abscess or gangrene, or their progress may terminate in the production of scars. Ulceration may occur in consequence of the extension of an inflammatory process to the surface, or it may result in the course of the degenerative softening of a tumor. In both cases the cutaneous or mucous surface is involved and destroyed, and the interior of the tumor being exposed putrefactive processes, with fistulæ and sinuses, arise, the latter favoring the retention of the product and the persistence of the inflammatory process.

Tumors are always pathological, but the resulting disturbances vary within wide limits and are often of a complex character. The familiar distinction between benignant and malignant tumors is based chiefly upon this variance in the nature of the disturbances. Those are benignant which closely resemble the normal structures of the body, increase but slowly, and, if they attain a large size, produce mainly mechanical disturbances. They may prove serious, even fatal, if so seated as to interfere with the function of important parts of the body. Very large and heavy tumors may prove burdensome solely on account of their weight, while others of similar character, elsewhere seated, may interfere with respiration or circulation, and eventually with nutrition. Tumors in exposed situations may become important only in virtue of their liability to injury, while others impede the function of a part or an organ by pressure upon its nerves and vessels or by obstructing its ducts.

The malignant tumors, on the contrary, differ in their structure from the normal tissues of the body. Their growth is rapid and infiltrating rather than slow and concentric. Such tumors usually have a predominance of cells and thin walled blood-vessels. The former may be little else than nuclei enveloped in an easily destructible protoplasm, or they may be composed of multi-nucleated masses of protoplasm, and are then known as giant-cells. The most malignant tumors are those which tend to become generalized as well as to spread locally. They recur locally, and appear in the nearest lymph-glands and at remote parts of the body. The disturbances produced by the malignant tumors depend less upon their mechanical relations than upon their tendency to destroy tissues and disturb functions. With their presence and progress in vital organs there is associated, from their manner of growth, a destruction of the cells of such organs, as the kidneys and liver, the lungs and heart. When they are seated in the spleen and lymphatic glands, a disturbance in the blood-making process must be associated. Their occurrence in the alimentary canal opposes the admission, digestion, and expulsion of its contents, and produces disturbances varying as to the seat and peculiarities of the tumor. The progress of the malignant tumor is often associated with ulceration, watery discharges, and hemorrhage. The frequent coexistence of emaciation, weakness, anæmia, and a yellowish discoloration of the skin forms a group of disturbances which, included under the name "cachexia," have long been prominent as significant of malignant tumors. At the present day this cachexia is regarded rather as the result than the cause of the tumor, whereas formerly the reverse was the case.

The modern classification of tumors is based chiefly on their structure, in part upon their method of origin, and in part upon their cause.

With the observation of the similarity of appearances in the flesh of which the external and internal neoplasms are composed, the suggestion readily presented itself to regard the external tumors and the internal growths as similar in character. External forms, physical characteristics, clinical peculiarities, all proved insufficient as a means of identifying the two, and the step was a short one which led to the minute study of the flesh of the tumor and a comparison of its resemblances and differences. This comparison obviously included a knowledge of the structure and peculiarities of normal tissues. As histological studies advanced, so did the pursuit of pathological histology, and the tumors which were once designated as encephaloid, mastoid, pancreatoid, or nephroid, from real or fancied resemblances to certain organs of the body, became analyzed into their microscopic rather than macroscopic characteristics.

It is unnecessary to say that the modern classification of morbid growths owes its foundation and a large part of its superstructure to Virchow, whose classic work, Die Krankhaften Geschwülste, showed the direction which future investigators were to pursue and the nature of the discoveries likely to result.

The tumor represents the result of the growth of a tissue or tissues which are like or resemble those which form the normal constituents of the body. Although a new formation is present, it is composed of tissues lying within the possibilities of the individual. A new formation of feathers, as Virchow suggests, is beyond the productive powers of human tissues, though within those of feathered animals. A goose can produce a tumor containing feathers, not one in which hairs are found; in the human species tumors containing hairs may occur, not those, however, in which feathers are present. Although the cells of the tumors of man may deviate in their appearances from the cells of normal tissues, this deviation is never so extreme that their analogue cannot be met with in some part of the body.

As the normal tissues originate from pre-existing tissues, so the pathological tissues of the tumor grow only from the antecedent tissues. The matrix from which the tumor arises is a normal tissue. There is produced from it, as a neoplasm, either a tissue which follows the type of the maternal tissue, a homologous tumor, or one which deviates in type from that of the matrix, a heterologous growth. Although the latter differs in its composition from that of the matrix, it does not vary essentially from a like tissue to be found elsewhere in the body. It occurs where it does not belong either in place, time, or quantity. The homologous tumor appears rather as a hypertrophy of the tissue from which it arises, and the line between this variety of growth and a simple hypertrophy is often purely arbitrary.

Although tumors, in the more limited sense, are solid, fleshy masses, the new formation of tissues may result in the presence of a tumor within which is a cavity with various contents. Such a cavity is not a mere hole, but has a distinct wall of connective tissue lined with epithelium or endothelium. A distinction is thus drawn between cysts and growths—one which is of daily importance in the practice of medicine—and Virchow's oncology includes the consideration of the two varieties of tumors.

Cystic tumors are subdivided according to the nature of their contents and the method of their origin. One group is composed of clotted blood within cavities resulting from the laceration of tissues or in preformed spaces. If the cyst primarily is merely a rent, the wall becomes thickened in time from a growth of the limiting tissues, and the blood-clot, of which the tumor was chiefly composed, may remain or become absorbed. If the latter event occurs, its place of deposit may become obliterated by a fusion of the walls of the cyst, or may persist from the subsequent addition of serum.

The cystic tumor whose contents are extravasated blood is the hæmatoma, familiar instances of which are met with in the hæmatoma of the dura mater, of muscle, of the vulva, and the polypoid hæmatoma of the uterus. The latter is the long retained and constantly enlarging blood-clot, due to the adherence of portions of the placenta after childbirth.

The second group of cystic tumors has for its contents a more watery fluid, and to this the term hygroma is applied. This watery fluid lies, for the most part, within preformed cavities, and its accumulation is connected with a dilatation of these cavities. Instances are met with in the tumors resulting from the accumulation of fluid in the membranes of the brain or spinal cord, and in the ventricles of the former or in the central canal of the latter. These lead to the congenital cystic tumors of the cranium or spine, with watery contents. The ganglion, the house-maid's knee, as also the hydrocele of the tunica vaginalis, are regarded as hygromata. The hydrocele of the neck and elsewhere in the subcutaneous or intermuscular connective tissue is now removed from the hygromata to the tumors which arise from lymph-vessels. A like transfer of other hygromata might be made in accordance with the prevailing views concerning the cavities in which the watery fluid is accumulated.

A third group of cysts contains material which represents essentially a production from the wall, with a difference of composition dependent upon the nature of the wall. Such cysts give rise to tumors through the retention of their contents, and they are called retention-cysts or retention-tumors. In the wall of the cysts is a gland-tissue, which may line the surface or lie beneath. The glandular structures may be cutaneous, mucous, or represent a part of the great glands of the body, as the liver and kidneys. The atheromatous cyst of the skin, the mucous cysts of the gastro-intestinal mucous membrane, and the ovula Nabothi of the uterus are examples of the retention of secretion within glands. The dropsical dilatations of the antrum, the vermiform appendage, the uterus, the biliary and renal canals furnish instances of tumors resulting from the retention of secretion on a large scale. In the subsequent history of these retention-cysts the secretion may be modified chemically and physically; the cells upon the walls may be transformed from columnar forms into flattened and scale-like varieties. In time, the original secretion frequently becomes a watery fluid, resembling the contents of the hygroma previously mentioned.

This grouping of cysts in contradistinction to fleshy tumors omits the consideration of a series of cystic tumors of enormous size, the multilocular tumors of the ovary. This class represents a more complex form of cystic growth—one whose tendency is toward the reproduction of cysts, to which the term cystoma is applied. The cystoma is the result of an active new formation of epithelium and connective tissue, and is classified as a variety of the epithelial group of tumors.

Morbid growths, as distinguished from cysts, are divided by Virchow into the simple and complex forms. The former consist of a single tissue, the histoid tumors; the latter of several tissues suggesting an organ, the organoid tumors; while still others, in which the number and grouping of tissues is so complex as to simulate systems of the body, even monstrosities, have received the term systematoid or teratoid tumors.

Virchow claimed that the growth of most tumors took place from the connective tissues, and that most of the organoid tumors, especially cancer, arose from the formative action of the connective tissue in the part where it first made its appearance. The structure of cancer suggested an organ, as it consisted of collections of cells resembling epithelium, within spaces or alveoli whose walls were formed of connective tissue. The epithelioid cells of the cancer, as well as the connective-tissue corpuscles, were considered to arise from pre-existing cells of connective tissue.

The first, most important, modification of Virchow's views, which has led to a more rational appreciation of the relation of the various tumors, especially of the epithelial group, to each other, arose in consequence of the investigations of Thiersch and others with regard to the origin of certain cancers. This observer⁸³ claimed that the epithelioid element of cutaneous cancers arose in all instances from pre-existing epithelium, either of the rete mucosum or cutaneous glands. Similar views were suggested, with various degrees of precision, by other authors concerning certain cancerous tumors elsewhere, but were first applied to all cancers with a more exact formulation by Waldeyer,⁸⁴ to whom the prevailing views with regard to the histogenesis of morbid growths are due. According to him, the essential (epithelioid) element of all primitive cancers arises from pre-existing epithelium; consequently, no cancer-cell can arise except in organs where epithelium is normally present.

⁸³ Der Epithelial Krebs, namentlich der Haut, etc., 1865.

⁸⁴ Virchow's Archiv, 1867, xli. 470; 1872, lv. 67; Volkmann's Sammlung klinischer Vorträge, 1871, xxxiii.

This comprehensive statement was rendered possible by the embryological researches of Remak at the outset, and afterward by those of His and Waldeyer. Remak showed that after differentiation of the cells of the ovum into the several germinal layers, those from one layer could not serve to originate the cells belonging to another layer. The development of normal tissues takes place within the limits defined by this differentiation. Epithelium thus is not derived from connective tissue, nerves, or muscles, nor was the reverse known to occur. To His is due the exact appreciation of the superficial cells of serous membranes, which had been previously called epithelium, and had thus been confounded with the epithelial cells of mucous or cutaneous membranes and of secretory glands. He showed that these cells had a wholly different origin from epithelium, and were simply scale-like cells of fibrous tissue, to which he applied the name endothelium. The latter is now used as the term for the thin, squamous cells of fibrous tissue, whether they are found lining the walls of the great serous cavities or the smaller lymph-spaces, the endocardium, or the inner coat of blood-vessels and lymphatics.

The importance of this distinction is obvious when the occurrence of tumors, called cancers, is observed in parts which contain no epithelium. Aside from the vagueness of the term cancer, as applied clinically, tumors are sometimes met with, even in parts where epithelium normally does not exist, whose structure resembles more or less closely that of cancer as usually recognized. Such tumors are to be regarded as of an endothelial rather than epithelial character, and as such their histogenesis falls under the general laws of the development of tissues.

Waldeyer⁸⁵ has suggested that the primitive basis for the development of the genito-urinary tract contains cells which are equivalent in their possibilities of ultimate development to the epithelium of the limiting germinal layers—a suggestion which is of importance in permitting the epithelial tumors of the ovary to be brought under the general embryological laws of development.

⁸⁵ Eierstock und Ei, 1870.

As the growth of embryonal tissues is so defined that descendants are like their ancestors in all respects, so the development of tissues in the adult is regarded as defined with equal precision. Eberth and Wadsworth⁸⁶ have shown that the regeneration of corneal epithelium takes place from pre-existing epithelium. E. Neumann and others claim in like manner the development of muscular tissue from antecedent muscular cells.

⁸⁶ Virchow's Archiv, 1870, li. 361.

The relation of cancer to epithelial tumors is regarded as similar to that borne by sarcoma to tumors composed of connective tissues. The growth of the epithelial elements into the neighboring parts is through paths determined by pre-existing or new-formed connective tissue. The active element of the cancer lies more especially in its epithelioid cells, and its growth takes place in an atypical rather than a typical manner. Of the various epithelial tumors, there are those like the cutaneous horn or corn, the adenoma or cystoma, whose epithelial growth takes place in accordance with normal methods of production. The epithelioid constituent of the cancer, on the contrary, grows often with great luxuriance and with but little tendency to carry out the normal mutual relations of the epithelium and connective tissue of the part from which it proceeds. The epithelioid masses or sprouts are composed of cells whose relation to each other resembles that of normal epithelium in the absence of an intercellular substance, while the shapes of the cells correspond more or less closely with that of the epithelium in the region from which the tumor arises. The epithelioid cells of cutaneous cancers resemble those of the surface, the rete, or the glands of the skin. Cancers of the stomach or uterus contain epithelioid cells whose shape simulates the varieties in the stomach and uterus. Such resemblances are carried out in the degenerations which the cells of cancer undergo. The horn-like, keratoid, transformation of epidermoid cells in cutaneous cancers, the mucous degeneration of the epithelioid cells of cancers of mucous membranes, are sufficiently familiar. Notwithstanding these resemblances, which are also present in secondary tumors at remote parts of the body, the epithelioid growth advances without limit and without reproducing the normal type. Cancer is therefore defined as an atypical, epithelial new formation.

Sarcoma, on the other hand, whose clinical features correspond so closely with those of cancer, simulates, as shown by Virchow, the connective tissues. It is composed of cells and intercellular substance, both of which may be as varied as are those of the connective tissues. The shape of the cells is as diverse and their contents as various, while their possibilities of degeneration are alike. The cells of the sarcoma are not simply cemented together, as are epithelial cells, but they are separated from each other by an intercellular substance, which corresponds in its appearance and chemical properties with that of mucous, fibrous, cartilaginous, or osseous tissue. The structure of the sarcoma differs from that of these tissues in presenting a predominance of cells over intercellular substance, while the reverse is the characteristic of most varieties of connective tissue. In this predominant cell-formation lies its absence of type, whereas the atypical character of the cancerous growth is manifested rather by the irregular grouping of the cellular masses than by an abundance of cells.

As the original cancer is considered as possible only in parts where epithelium is a normal constituent, so the primitive sarcoma is possible only in parts where connective tissue is present. The apparent great frequency of sarcoma in recent times is thus obviously explained. With an agreement as to its histological characteristics, its possible place of origin is any of the connective tissues of the body, and their presence is universal. In the manner of its growth, its recurrence, and generalization it is subject to the same laws which determine similar events in the history of cancer. Its degenerations are often the same, and its symptoms are due to the action of like causes.

The importance of distinguishing between these atypical tumors is real, in that it is only through the association of causes, symptoms, and results with defined and constant characteristics that a practical knowledge of tumors is to arise. The time-honored distinction between malignant or semi-malignant and benignant growths is always to be sought for, and can only be fully possessed when the natural history of the new formations is known. With an exact appreciation of the structure of a tumor it becomes possible to study its special pathology. From a knowledge of the latter are to be derived those features of importance in determining the relation of morbid growths to other deviations from normal and physiological processes. An immediately practical benefit arises from the Thiersch-Waldeyer modification of Virchow's theory of the origin of tumors, in that it permits with greater ease a more accurate clinical diagnosis. Lücke⁸⁷ has been prominent in calling attention to the suggestions thus presented.

⁸⁷ Volkmann's Sammlung klinischer Vorträge, 1876, xcvii.

The diagnostic value of the theory above-mentioned is rather negative than positive. With rare exceptions, a tumor cannot be epithelial in character if its origin is from an organ or a part in which epithelium is absent. The possible exceptions admit theoretical explanations which present considerable degrees of probability, and are also based upon the existing views of the development of tissues.

A tumor whose origin from the connective tissues is determined partakes of the characteristics of its matrix, and is a connective-tissue tumor. Its development from fibrous tissue is more likely to result in a fibroma; from fat tissue, a lipoma, or a myxoma; from cartilage or bone, a chondroma or osteoma.

Tumors developing at certain periods of life in certain parts of the body are more likely to belong to one than another of the histogenetic groups. Tumors of the connective-tissue series are stated by Lücke as more prevalent before the age of thirty-five years, while those of the epithelial group are more likely to occur after this age, and cancer of the lip is of special frequency in old age. The fibro-myoma is of most frequent occurrence in the uterus, and rarely attains a large size till the approach of the climacteric.

The rapidity of growth of tumors is also associated with their genesis. It has previously been stated that the more rapidly growing tumors are those whose cells are most abundant and in the closest and most intimate relation to blood-vessels. The type of such tumors is the sarcoma with its scanty intercellular substance, while the other (histoid) tumors in the same series, as the fibroma, lipoma, chondroma, etc., are of relatively slow growth. Tumors of the epithelial series are of slow growth, from the constantly increasing distance of the new-formed cells from the vascular connective tissue which provides their nourishment. When, however, the growth of the epithelium advances into the connective tissue, pushing out in all directions and coming in contact with new series of vessels, the opportunities for nutrition are favorable. In like manner, when the new formation concerns the connective-tissue stroma, as well as the epithelial sprouts, vascularization proceeds with the development of the tumor, and favorable conditions for rapid growth are presented. Large epithelial tumors may thus arise within organs, but, as the surfaces are reached, the sources of nourishment become farther removed and the degeneration of the epithelium favors its detachment and the formation of ulcers. Hence the tumors whose advance is associated with ulceration belong rather to the epithelial than the connective-tissue group.

The tendency of the cancerous tumors to become generalized through the lymphatics, and that of sarcomatous growths through the blood-vessels, is admitted as an important feature in the differential diagnosis. Although there are numerous exceptions, the rule is available. Its explanation is based upon the assumed inability of the larger epithelial cells of the cancer to pass through the lymph-glands; being detained, they serve as new centres of growth. The smaller cells of the sarcoma, on the contrary, are permitted a passage through the gland. The numerous and thin walled blood-vessels present in the rapidly growing sarcoma permit an extension of the latter into their interior, and thus a ready opportunity is offered for the formation of emboli.

Another important modification in the classification of tumors has resulted from the recent discoveries regarding the nature and effects of infective agencies. Virchow grouped together under the term granulomata certain growths composed of granulation-tissue occurring in syphilis, lupus, leprosy, and glanders. Their relation to inflammatory processes was very intimate, yet they were recognizable as tumors from their possession of many of the characteristics generally admitted as belonging to such morbid growths. Although at times their presence might be regarded as evidence of an inflammatory disturbance, their frequent appearance independently of general symptoms of the latter was apparent. These tumors, furthermore, were so frequently accompanied by inflammatory products as to suggest a like cause for both. Virchow stated that the recognition of the etiology of these tumors was indispensable to their separate consideration, and laid stress upon the presence of a specific virus, contagious and infectious, in the case of syphilis. His views concerning the etiology of leprosy, though more guarded, yet carried the suggestion of the importance of exact investigation concerning the assumed contagious character of this disease. The contagiousness of glanders was not only admitted, but the similarity of its manner of origin and propagation to the invasion of syphilis was also stated. Not only were the resemblances between glanders and syphilis recognized, but lupus, leprosy, tubercle, and scrofula were also admitted as presenting a similar relation.

The importance of recognizing the etiology of these tumors rather than their anatomy as a basis of classification was strongly urged by Klebs,⁸⁸ who proposed the term infective tumors for the group of granulomata, including syphilis, lupus, leprosy, and glanders; and for tubercle, scrofula and the pearly distemper of animals, which Virchow had classified as lymphomata. This group has been still further extended by the addition of the lymphomata occurring in typhoid fever, scarlet fever, and diphtheria. Ponfick⁸⁹ has recently added the disease actinomycosis to the series, and Cohnheim suggests that certain of the lympho-sarcomata may be similarly classified.

⁸⁸ Prager Vierteljahrschrift, 1875, cxxvi. 116.

⁸⁹ Die Actinomykose des Menschen, 1882.

The growths thus included have a common element of structure—the granulation-tissue, with its possible disappearance through absorption or its transformation into an abscess or dense fibrous tissue. Such features are those common to the granulation-tissue resulting from ordinary inflammation. Their essential characteristic, however, lies in the etiology of this granulation-tissue, and for many members of the group the cause has been discovered to be microscopic organisms. The constant presence of these is determined in sufficient numbers, in such distribution, and in such relation, as to explain the nature and occurrence of the tumors.

The evidence recorded is not equally full and exact for all members of this group. Neisser⁹⁰ has discovered the bacillus of leprosy, and the discovery by Koch⁹¹ of the bacillus of tuberculosis, scrofula, and pearly distemper has already been referred to. Schütz and Löffler⁹² have lately announced their isolation of the micro-organism causing glanders, and Bollinger⁹³ discovered the fungus whose presence is necessary for the existence of actinomycosis.

⁹⁰ Virchow's Archiv, 1881, lxxxiv. 514.

⁹¹ See page [99].

⁹² Deutsche medicinische Wochenschrift, 1882, lii. 707.

⁹³ Centralblatt für die med. Wissenschaften, 1877, xxvii.

In the above affections the organisms are to be regarded as the characteristic active agent in producing the phenomena of the disease in which they occur. The presence of micro-organisms in syphilis, typhoid fever, scarlet fever, and diphtheria is admitted, yet their absolute identification and constant presence as a cause of the various manifestations of the respective diseases still remains to be proved.

The classification of tumors herewith presented is essentially that of Virchow, with such extensions and modifications as have arisen in consequence of the investigations and discoveries during the twenty years which have elapsed since the delivery of his memorable series of lectures. Cysts are mentioned, as well as growths, from the importance of the former in practical medicine. The frequent simultaneous occurrence of cysts and growths in the same tumor should be mentioned, and the cystic feature is usually indicated as a qualification.

CYSTS.

Cavities, either new formed or pre-existing, with various contents. The latter are blood, liquid other than blood, and gland-secretion or retained secretion. The wall varies in structure in accordance with the method of origin of the cavity.

Hæmatoma.

A collection of extravasated blood, usually within the tissues. Examples, hæmatoma of the pericranium (periosteum), of the external ear, muscle, dura mater, ovary, broad ligament, vulva, anus, uterus (from retained placenta), hæmatocele, dissecting aneurism.

Hygroma.

A collection of transuded or exuded fluid in pre-existing or new-formed spaces. Examples, hydrocele, hydromeningocele, hydromyelocele, hydrencephalocele, ganglion, inflamed bursa.

Retention-Cyst.

An accumulation of retained secretion in follicles or canals from obstruction to its escape. Examples, atheroma and comedo of the skin, mucous cysts of the gastro-intestinal mucous membrane, ovula Nabothi, and cystic polypus of the uterus; retention-cyst of the antrum, vermiform appendage, gall-bladder, and bile-ducts; dropsical dilatation of the ovarian follicles, Fallopian tube, uterus (hydrometra), parovarium (cyst of the broad ligament); hydronephrosis and multilocular cystic kidney, spermatocele, ranula, galactocele.

The growths are classified according to the tissues of which they are chiefly composed and from which they originate, and according to their etiology. There are consequently the connective-tissue group; that of tissues of higher function, as muscle, nerve, and vessels; and the epithelial group, in which the new formation of epithelium is the essential feature. The teratoid group comprises a more complex massing of tissues, representing a combination of those derived from all the germinal layers of the embryo. The infective group includes those tumors whose structure is closely allied to that of the products of inflammation, but whose origin is the direct result of the introduction from without of a microphyte.

CONNECTIVE-TISSUE GROUP.

Each member mainly composed of a more or less typical growth of a connective tissue:

Myxoma,
Lipoma,
Glioma,
Chondroma,
Fibroma (including papilloma and melanoma),
Osteoma.

To these are added tumors composed of an atypical growth of a connective tissue, chiefly manifested by a predominance of cells:

Endothelioma,
Sarcoma.

The sarcoma includes as many varieties as there are tissues in this group, hence,

Myxosarcoma,
Liposarcoma,
Gliosarcoma,
Chondrosarcoma,
Fibrosarcoma, melanosarcoma,
Osteosarcoma.

GROUP OF TISSUES OF HIGHER FUNCTION.

Myoma, of striped (rhabdomyoma) and smooth (leiomyoma) muscular tissue,
Neuroma, of nerve tissue,
Angioma, of blood-vessels,
Lymphangioma, of lymphatics,
Lymphoma (?), of lymph-gland tissue.

EPITHELIAL GROUP.

Epidermis:

Callus,
Corn,
Keratosis,
Horn,
Onychoma.

Epithelium of mucous membranes or glands:

Struma (?),
Adenoma,
Cystoma.

In the above varieties the growth of epithelium is more or less typical, a simple hyperplasia, either alone or combined with the new formation of fibrous tissue. Only the last three members of the series are tumors in the limited sense.

CANCER.

Cancer remains as an epithelial tumor, representing the atypical growth of cells resembling epidermis or the epithelium of glands and mucous membranes, extending into parts where epithelium is not found as a normal constituent. A new formation of connective tissue is usually associated with that of the epithelial cells.

Numerous varieties of cancer are described, according to the physical and structural peculiarities of the tumor. The scirrhus and encephaloid of the earlier writers are now transformed into fibrous and medullary cancer. This change in name is due to the stress laid upon the predominance of the fibrous stroma as the usual cause for the hard, dense, scirrhous cancer, while an abundance of epithelioid cells in relatively large alveoli is present in the encephaloid, marrow-like, medullary variety.

When the growth takes place from the skin or mucous membranes, the surface frequently presents numerous and usually arborescent papillæ or villi. The papillary cancers of the skin and the villous cancers of mucous membranes are thus distinguished.

Cancerous growths of the skin and transitional membranes, often called epithelioma or cancroid, usually contain epithelioid cells resembling epidermis, and are therefore designated as epidermoid or pavement-celled cancer. The alveolar contents of certain cutaneous cancers are cells resembling those of the deeper layers of the rete mucosum, while those of other cancers of the skin resemble rather the epithelium of sweat-glands. Growths of the former character extend laterally, ulcerate early, and are known as superficial cutaneous cancer. They form one of the varieties of the so-called rodent ulcer. Cutaneous cancers, simulating in their structure a reproduction of the epithelium of sweat-glands, represent a variety of glandular cancer. The latter term is applied to cancerous growths which arise in glandular organs, with suggested resemblances of their cells to the gland-cells of the respective organ. Cylindrical-celled cancer is frequently met with in those parts of which a cylindrical epithelium is a normal constituent.

The degenerations of the epithelioid cells and stroma suggest qualifying terms. The mucous and colloid cancers are those whose alveolar contents or stroma have undergone a mucous or colloid degeneration. The keratoid cancer is one which presents the horn-like transformation of its epidermoid cells. The melanotic cancer contains abundant pigment, melanin, within its cells.

These differences in the structure and appearance of the tumor are frequently associated with certain modifications of growth and clinical properties. The epidermoid cancers are less likely to recur after early removal; the medullary cancers are of rapid growth and prone to ulceration; while the fibrous or scirrhous forms are of extreme slowness of growth. In general, however, the pathological importance of cancerous tumors is essentially the same wherever the seat and whatever the peculiarities of structure.

TERATOID GROUP.

Includes those tumors, usually of congenital origin and apparent at birth, composed of connective tissue, epithelium, nerves, muscle, and vessels. These tissues are often so grouped together as to suggest systems of the body and parts of an individual. Cysts are often present which simulate cavities found in the body, whether of normal or pathological origin.

In this group are the dermoid cysts with their various contents, epidermis, sebum, hair, teeth, and bone. The solid teratomata, with all varieties of connective tissue, as fibrous tissue, fat tissue, cartilage, bone, neuroglia, in addition to nerves, muscle, and vessels. Squamous, cylindrical, and ciliated epithelium may be present and line cavities, at times tubular, whose walls are formed of skin or mucous membrane. Other tumors of this group are commonly included under monstrosities, and comprise the varieties of duplication of parts of the body, of which the extreme instances are such double monstrosities as the Siamese Twins, Ritta and Christina, the Spanish Cavalier, and the like.

INFECTIVE GROUP.

The chief characteristic is the cause, micro-organisms, which, introduced into the body, produce, through their dissemination and development, multiple growths of tissue like those resulting from persistent inflammation. As their structure corresponds with the productive results of inflammation, and their cause is analogous to the infective causes of inflammation, these morbid growths are closely allied to inflammatory disturbances. Their classification among tumors is desirable, as they represent circumscribed growths whose appearance, persistence, and effects closely resemble those characteristics of the morbid growths, in the limited sense, in which the new formation of tissue occupies a wider range:

Granuloma of tuberculosis, scrofula, leprosy, glanders, actinomycosis, syphilis, lupus.
Lymphoma of diphtheria, scarlet fever, typhoid fever.