Chapter II: Part II: , Showing Predominance of Malarial Element . . . . 617 (1)

GENERAL PATHOLOGY.

GENERAL MORBID PROCESSES.

GENERAL ETIOLOGY.

HYGIENE AND QUARANTINE.

DRAINAGE AND SEWERAGE IN RELATION TO THE PREVENTION OF DISEASE.

{35}

GENERAL MORBID PROCESSES.[1]

INFLAMMATION; THROMBOSIS AND EMBOLISM; EFFUSIONS; DEGENERATIONS; TUBERCULOSIS; MORBID GROWTHS.

BY REGINALD H. FITZ, M.D.

[Footnote 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 Virchow[2] 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. {36} Another link is to be found in the fatty degeneration resulting from this lack of blood.

[Footnote 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.

{37} 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.

[Footnote 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 {38} 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.

[Footnote 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 Rosenthal[5] 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.

[Footnote 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, Rosenthal[6] disputes this {39} 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.

[Footnote 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. Wood[7] 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.

[Footnote 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.

[Footnote 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 Wood[9] 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 {40} 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.

[Footnote 9: _Op. cit._, 236.]

[Footnote 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.

[Footnote 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 {41} 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 Samuel[12] 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.

[Footnote 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.

{42} 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 Reuss[13] 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 {43} 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.

[Footnote 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 {44} 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.

{45} 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.

[Footnote 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.

{46} 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.

[Footnote 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 {47} 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 {48} 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 {49} 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 {50} 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.

{51} 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 Formad[16] 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.

[Footnote 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.