Cornell University Library 
 RB 131.Eg5 
 
 Syllabus of lectures on inflammation. 
 
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 1897 
 
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 -i<^. 
 
 
 SYLLABUS OF LECTURES 
 
 ON 
 
 INFLAMMATION 
 
 AND ASSOCIATED CONDITIONS 
 
 BY 
 
 JAMES EWING. M. D. 
 
 DEPARTMENT OF PATHOLOGY 
 CORNELL UNIVERSITY MEDICAL COLLEGE- 
 NEW YORK CITY 
 
 1905 
 
Cornell University 
 Library 
 
 The original of tiiis book is in 
 tine Cornell University Library. 
 
 There are no known copyright restrictions in 
 the United States on the use of the text. 
 
 http://www.archive.org/details/cu31924000326912 
 
INFLAMMATION 
 
 AND ASSOCIATED CONDITIONS 
 
 Definition: — Inflammation may be defined as the organized 
 reaction of tissues to injury. 
 
 The historical conceptions of inflammation present three 
 phases, each of which forms the basis of current views regarding the 
 nature and scope of this process. 
 
 (1) The external signs presented by some inflamed vascular 
 tissues, viz., redness, heat, pain, swelling, and disturl)ance of func- 
 tion, were first regarded as the cardinal features which distinguish 
 the inflammatory process from other tissue changes. 
 
 To-day many authors and the layman apply the term inflamma- 
 tion only to such processes as show the deflnite vascular disturl)ances 
 which give rise to these cardinal signs. Practically it is very 
 convenient to limit the term in this way, but the micro- 
 scopical and comparative stiTcly of inflammation very soon discloses 
 that vascular changes constitute only a part, and often a very sub- 
 ordinate part, in processes which are identical in significance with 
 those in which vascular changes are prominent. 
 
 (2) Virchow regarded as the essential element of inflammation 
 a disturbance of nutrition of tissue cells. This disturbance is brought 
 about by irritants which cause alterations in the life processes of the 
 cells marked by a tendency to degeneration, often by vascular changes, 
 and usually by efforts at regeneration. This philosophical concep- 
 tion recognizes that degeneration, exudation, and regeneration are 
 essential features of one complete process. Such a theory however 
 which regards all the nutritive, formative, and functional results of 
 irritation as inflammatory is generally regarded as too comprehen- 
 sive, and robs the term of much of its practical utility. 
 
 (3) The teleological conception of inflammation as the pur- 
 poseful reaction of the tissues to injury, furnishes the deepest insight 
 into the true nature and scope of the pirocess, and separates it from 
 many other tissue changes, such as atrophy, hypertrophy, tumor 
 growth, and ordinary functional changes in cells. According to this 
 
view, inijiunmation inchidcs all the changes which injured tissues 
 undergo as the direct result of tlie injury and which are comprised 
 under the terms degeneration, exudation, and regeneration. 
 
 Etiology. The variet\- of factors concerned in inflammation is 
 very great. Those agents the presence of which directly induces the 
 inflammatory process are called exciting cauaes. The principal excit- 
 ing causes are mechanical trauma, heat, electricity, the X-ray, chemi- 
 cals, and microorganisms. While all but the last of these causes fre- 
 cjuently act in pure form exciting various grades of inflammation in 
 direct proportion to the quantity of the agent present, microorganisms 
 seldom figure alone as causes of inflammatory reaction. The mere 
 presence of bacteria is usually not sullicient to. excite inflammation of 
 a superficial tissue; there must usually be also secondary contributing 
 causes such as a wound, or exposure to cold, or local disturbances of 
 metabolism, or general predisposition on the part of the individual. 
 In the etiology of bacterial diseases are commonly associated (1) ex- 
 citing, (3) contributing and (3) predisposing factors, {lllus. 'Tu- 
 berculosis in different individuals, pneumonia in different seasons and 
 races.) Even with the simpler chemical agents, contributing and 
 predisposing factors are often of great importance in determining 
 the grade of inflammation. {IIIvs. Toxic effects of siraiuherries, lob- 
 sters, etc., antagonism between gonl and tuberculosis). The accurate 
 estimation of the relative importance of exciting and contributing 
 causes of inflammation is often extremely important and dilKcult. 
 (lllus. Infection of mice by the pneumococcus. Development of in- 
 fectious diseases in all animcds. Relation of intestinal hacteria ta 
 in fan tile diarrli oea. ) 
 
 The chemical excitants of inflammation include not only those 
 which reach the body from without in the form of irritants and 
 escharotics, but also those which develop within the body in the 
 form of abnormal secretions and poisonous products of disturbed 
 general or local metabolism. From the latter source ari<e many of the 
 inflammations occurring in the course of the auto-intoxications. 
 The contributing and predisposing causes of many bacterial inflam- 
 mations are often found to consist in the influence of such endo- 
 genous poisons. (lllus. Nasal calairh, uric acid in gout, terminal 
 infections in uremia.) 
 
 The grade and character of the inflammations excited by various 
 agents areusually of somewhat definite type. (Burns, X-ray. tubercle 
 bacillus.) 
 
it is an important fact that the first five of the etiological agents 
 mentioned, -when acting alone, while sometimes producing inflamma- 
 tion of pm-ulent grade, 3-et are usually followed by less intense grades 
 or other types of reaction, and that the vast majority of purulent 
 inflammations are of bacterial origin. . 
 
 All pathogenic bacteria may, but many seldom do, excite puru- 
 lent inflammation. A purulent inflammation is almost never of 
 purely tuberculous origin. {Tlie pyogenic bacteria.) In general, 
 bacteria excite exudative or productive inflammations with self-per- 
 petuating tendencies, while other agents induce non-purulent processes 
 of self -limiting type. {Pneumonia, Burns.) Protozoa as a rule 
 excite little inflammatory reaction in the tissues they infest. They 
 consume tissue cells and cause degeneration and multiplication of 
 cells, but disturb the organism chiefly through the action of endo- 
 genous poisons which result from their growth. (Malariti, piro- 
 plasmo.sis, sypliilis?) 
 
 The Action of Microorganisms in Inflammation. 
 
 Mode of Entrance. Microorganisms usually enter the body 
 and reach a position where they ar6 capalfle of inducing disease 
 through passages lined by mucous membrane, respiratory, gastro- 
 intestinal, genito-urinary, etc. Previoiis inflammation of these 
 mucous passages or other form of lowered vitality very greatly favor 
 and are often essential to the further development of tlie invading 
 parasites. Through fresh wounds which may be of very minute 
 size pathogenic and non-pathogenic bacteria penetrate the skin or 
 mucous membrane, and finding conditions favorable to their develop- 
 ment the former go on to produce infectious diseases. When the 
 progressive development of bacteria in the body is required before 
 sufficient toxic material is present to produce symptoms the process 
 is called an infection. Simultaneous development of two or more 
 pathogenic microorganisms is called mixed infection. 
 
 Certain pathogenic bacteria excite a local inflammation which 
 occasionally offers a ready point of entrance for a second more viru- 
 lent microorganism, and the new germ begins at once to influence 
 or dominate the inflammatory process. Such an event is called 
 secondary infection. When bacteria live or multiply in the tissues 
 or cavities without producing any disturbance, the body may be said 
 to be infested, as when diphtheria bacilli live in the throat or typhoid 
 bacilli in the intestines but fail to excite morbid symptoms. 
 
Some bacteria produce disea,se without entering the tissues- 
 {diolera), while the relation of some intestinal bacteria to the tissues 
 in d3'senter3^ and diarrhoea seems to be variable. 
 
 In any case the entrance of microorganisms and their further 
 development is often greatly favored by their association with various 
 chemical poisons which cause degeneration and necrosis of lining and 
 tissue cells. Syntoxic 'parasitism (Schleich) is a term applied to 
 some forms of rapid infection and destruction of tissues by Ijaetena 
 and toxic products as seen in post-mortem wounds, infection from 
 decaying meats, and in some cases of puerj)eral sepsis with retained 
 placenta. The intact skin may be penetrated by rubbing with some 
 very virulent bacteria (Belt, pestis). Frequently their entrance occurs 
 more slowly through hair follicles and sebaceous glands [ftijcosis) . 
 
 Some infectious agents are" inoculated through the skin by the 
 Mtes of insects. Mosquitoes in this way transfer malaria, filariasis. 
 and yellow fever, and the cattle sick carries Texas cattle fever. The 
 blood is reached tlwough the inflamed glands of mucous membranes, 
 gradually as in typhoid fever and gonorrhoea, or suddenly without 
 premonitory disturbance, as in epidemic meningitis where the organ- 
 ism pro])ably travels through the nasal mucosa. When infection of 
 the blood or internal viscera occurs in the absence of any lesion of 
 mucous or cutaneous surfaces by bacteria which ordinarily require 
 such aids to their entrance, the infection is said to be cryptogenic. 
 
 Mode of Action. Once within the body, in mucous passages, 
 serous cavities, or tissue spaces, the pathogenic action of bacteria 
 depends almost entirely upon the effects of poisonous principles 
 elaborated by the bacteria, and only to a very slight extent, usuallv, 
 upon the mechanical effects of their presence, ilechanical irritation 
 however constitutes an important part of the local influence of some 
 bacteria, as in the miliary tubercle. In anthrax in some animals 
 the absorption of nutriment by the excessive numbers of bacteria is 
 probably an important factor in this disease. In the veo-etable kino-- 
 dom there are diseases in which the pathogenic action of jjacteria 
 appears to consist almost solely in the absorption of nutriment from 
 the plant cells. (Corn yellows.) 
 
 The poisonous principles arising in the course of bacterial infec- 
 tions of the animal body are very numerous and complex. Thev 
 comprise: (1) Principles derived from the disturbed metabolism or 
 disintegrating proteids of tissue cells; (2) principles derived from 
 the disintegrating bodies of bacteria, toxalbumins (endolo.rins) , and 
 
s 
 
 (3) diffusible poisons secreted by the living bacteria {diffusible 
 toxins) . 
 
 (1) Ptomaines and Leucomaincs are cr3'stallizable alkaloids 
 produced from tissue-albumins by the action upon them of bacterial 
 growth. 
 
 (a) Ptomaines are alkaloids developed by non-pathogenic bac- 
 teria growing in dead animal matter. {Poisoning by decayed meat.) 
 They occur under some very peculiar conditions and their presence 
 in decayed flesh is often transitory. 
 
 {b) Leucoinaines are alkaloids developed by pathogenic bac- 
 teria growing in living tissues. 
 
 (c) Albiunoses and ainido-acids are derived from tissue proteids 
 during the course of bacterial infections and these contribute to the 
 local inflammatory changes and to the general toxic symptoms. 
 
 {d) Diffusible toxins similar to the true toxins of bacteria 
 have been isolated by Vaughan from tissue cells, and it is probable 
 that such ferment-like principles are concerned in the local and gen- 
 eral phenomena of inflammation and infection. 
 
 (3) Bacterial cell bodies which have autolyzed spontaneously 
 or been split up by various chemical procedures yield poisonous proteids 
 which are called toxalbumins, bacterio-proteins, or endotoxins. Some 
 bacteria induce disease largely or wholly through the action of their 
 endotoxins {typhoid and tubercle bacilli) ; while others which secrete 
 true toxins act secondarily by means of their endotoxins {diphtheria 
 and tetanus bacilli). The endotoxins consist of proteids and their 
 derivatives, and vary somewhat according to the method by which 
 they are prepared. They are usually intense local irritants and are 
 chiefly responsil)lc for the local degenerative, chemotactic, and exuda- 
 tive efliects of bacterial invasion, but they usually fail to produce the 
 specific symptoms of particular infectious diseases. 
 
 (3) Toxins are specific poisonous princij)les thrown off from 
 the living l^odies of pathogenic bacteria. Their chemical nature is 
 not understood. They are not proteids, having Ijeen produced by 
 bacteria and demonstrated in proteid-free fluids. 1uit they are usually 
 associated with proteids. 
 
 Several facts favor the belief that bacterial toxins are 
 ferments: (a) After the injection of toxins into the body several 
 Jiours must usually elapse before symptoms appear. (&) The action 
 of most toxins is dcstroved bv heating them to 58° C. for one hour. 
 
((■) Toxins are extremely active in verj' minute quantities, (d) Bac- 
 terial toxins usuall}' initiate a train of symptoms which closely re- 
 sembles the clinical disease produced by the particular bacterium. 
 
 It has been shown, chiefly through the studies of Buehner, that the 
 destruction of bacteria and tissue cells yields a series of proteid deriva- 
 tives which, according to the se^'erity of the initial injurj', are more 
 and more removed from the original proteids of these cells. The earlii-r 
 members of this series, alkali-albumen and hemialbumose are strongly 
 chemotactic for leucocytes and lesions iu which these slightly altered 
 proteids are produced are less severe and run a favorable course, 
 while those in which the proteids are more extensively altered 
 and peptone, leucin, tyrosin, and skatol are formed are more se^'ere. 
 these principles are not chemotactic, and the lesions run a less favor- 
 able course. 
 
 In the action of toxins upon tissue cells there are two distinct 
 processes concerned. 
 
 («) The chemical union of the toxin molecule with the pro- 
 teid molecule of the cell. 
 
 (6) The development of the toxic action. 
 
 If frogs are injected with a fatal dose of tetanotoxin at 0° (,'. they 
 do not develop tetanus although their nerve cells absorb the poison. 
 If they are then warmed tetanus develops at once. If there is no 
 chemical atflnity between the cell-proteid and the toxin there is no intoxi- 
 cation. Tetano-toxin unites readily with brain emulsion of the rabbit, 
 while emulsion of dog-brain absorbs very little of this poison. Hence the 
 rabliit is extremely susceptible to tetanus, the dog very slightly no. Some 
 bacterial toxins have affinities chiefly for one type of cell. Tetano-toxin 
 acts almost exclusively upon the nerve cells in rabbits, hence brain- 
 emulsion wiU absorb this poison in the test-tube, but emulsions of liver 
 or spleen have no such effect. 
 
 Bacterial inflammations are therefore complex and changing 
 procc ses e.vcited by the effects upon tissues of various poisons derived 
 both from the bacteria and from the diseased cells, and which by 
 chemical action cause degenerative changes and the subsequent train 
 of vascular and cellular processes. Different factors are at work in 
 different phases of the process which however must be regarded as 
 a unit}' from the time of invasion by the bacteria until the injured 
 tissues reach an equilibrium. 
 
 When considerable quantities iDtomaines, leucomaines and bac- 
 terial toxic albumens, etc., are injected or absorbed, profound con- 
 stitutional disturbance may result immediately without the further 
 development or invasion of bacteria. Such a process is called 
 intoxication. (Retained pJacrnta, crushed limbs, gangrenous appen- 
 dicitis.) During the course of bacterial inflammations constitutional 
 
symptoms are produced by the absorption of poisonous products by 
 the blood current and their distribution throughout the system. 
 This condition is called toxemia. ' 
 
 THE INFLAMMATORY PROCESS 
 
 When inflammation is considered in its entirety, the following 
 processes are found to be involved : — 
 
 Degeneration or death of tissue cells (initial injury). 
 
 Changes in the circulation. 
 
 Exudation. 
 
 Secondary degeneration and death of tissue. 
 
 Growth of new tissue. 
 
 The majority of inflammations include all these phases of 
 reaction, but one feature may be more prominent than the others 
 or almost exclusively present, and all may appear in a great variety 
 of combinations. Each requires consideration in detail and treat- 
 ment as a separate factor, but its full significance can only be appre- 
 ciated when viewed in relation to the entire series of phenomena 
 included in the complete reaction of tissues to injury. This entire 
 series of phenomena will first be rapidly sketched, and later each 
 will be separately considered more fully. 
 
 Initial Injury. 
 
 An initial injury and degeneration of tissue cells appears to 
 be an essential preliminary in all inflammatory processes. It is of 
 secondary importance whether the injury affects primarily the fixed 
 connective tissue cells, or the blood vessels, or the nerves of a part, 
 all of which may be simultaneously involved. ^lechanical injury 
 may merely divide these cells : heat, chemical agents, and bacteria, 
 may cause very great or \'ery slight alteration in the life processes 
 of the cells, but in e'^cry instance some grade of injury or initation 
 affecting the equilibrium of tiie cells appears to iJi-eeedc the more 
 readily recognizable changes of inflaumiation. The exact character 
 of the changes in tissue cells residting from the initial injury is 
 very imperfectly understood since they are of very delicate nature 
 and are rapidly obscured by other processes, chiefly by disturbance 
 in the blood vessels. Pending further progress in definite knowledge 
 in this field, tlie following factors ma}' be suggested as chiefly con- 
 cerned in the early tissue changes resultiug from the initial injury 
 
and preceding- the morphological changes in cell structure and in the 
 circulation. (1) Disturbance in the normal action of cell ferments. 
 
 (2) Loss of equilibrium or disturbance of the altruistic relations, and 
 interference with the normal access of nutriment, of the cells. 
 
 (3) Disturbance of innervation. These are some of the factors 
 comprising the ultimate mechanism by which the organization of a 
 tissue is maintained. 
 
 Reaction to Irritation among Protozoa. Very pure illustra- 
 tions of cellular reaction toward irritating substances are found in 
 the behavior of amoeljac and other protozoa toward foreign bodies. 
 The amoeba coming in contact with a solid particle encloses it. 
 If the particle is digestible a vacuole is formed about it and it is 
 digested; if not, the particle is soon extruded, or the amoeba flows 
 away. There is here illustrated tactile semihilitji of unicellular ani- 
 mals, subserving the nutrition of the amoeba in one case and its 
 protection against irritants in the other. 
 
 The observations of Stahl on a multicellular myxomvcete A cthal- 
 ium septiciim and on the plasmodiviu of Fiiligo have brought to light 
 the existence in these low animals of a pccidiar susceptibility toward 
 certain influences which is known as chemotaxis. 
 
 Aethalium sepHoum is an amoeboid oi'gauism wliicli when placed 
 on a m6istened surface near a drop of infusion of oak bark moves 
 actively toward and into the infusion. The plasmodium Fuligo is another 
 amoeboid organism, which when iilaced on a moistened surface near 
 a drop of 1% solution of salt at first moves away from the solution, 
 but later, especially if needing water, will approach and finally enter 
 the solution. 
 
 . These observations illustrate positive and negatice cheuiotaxis, 
 and the transformation of negative into positive chemotaxis by a pro- 
 cess of adaptation. C^hemotaxis may be defined as the attraction or 
 repulsion exhiliited by amoelwid cells toward foreign bodies. 
 
 In the metazoa the cells are differentiated into three layers, 
 ectoderm, mesoderm, and endoderm. In the lowest metazoa (e. g. 
 Astropecten) the mesoderm is comprisetl largely of wandering amoe- 
 boid cells. In these animals, possessing either vascular or nervous 
 symptoms, the reaction to injury ma>' be chiefly confined to the 
 wandering cells which engiobe and digest or expel foreign bodies 
 which have penetrated the ectoderm of the animal. To this property 
 of wandering cells to engiobe and digest foreign particles "Metchni- 
 koff has applied the term phagocytosis. 
 
All of these properties, tactile sensibilit}', negative and positive 
 chemotaxis, and phagocytosis, are present in inflammatory processes 
 in the higher animals, where they probably have the same signifi- 
 cance as in the lower animals. 
 
 Among the lower metazoa are seen some of the best examples 
 of a remarkable power of regeneration exhibited by injured cells. 
 If the body of cerianthus is incised, an entire new set of tentacles 
 is developed at the point of incision. When the claw of a crustacean 
 is broken off at the "breaking joint" an entire new claw is developed. 
 If the head of an earth worm is severed, a new head is developed, 
 but if the severed end is immediately replaced the parts grow together, 
 no new head is produced, and regeneration is suppressed. If the 
 crystalline lens of a salamander be removed the capsule produces a 
 •new lens; if the capsule is removed the iris produces a lens although 
 its cells are of different embryonal origin from the capsule cells. 
 
 The laws governing regeneration seem to show that this property 
 of cells and tissues is under the control of the orgatbizaiieii of the 
 affected animal, and produces results which are in some way adapted 
 to the animal's needs. The cells of higher animals all . possess in 
 some degree the capacity of regeneration which is exhibited in the 
 course' of reactions to injury and effects the repair of many injured 
 parts. It is here under the control of the organization^ and has the 
 same significance as in the lower animals. 
 
 Among the higher metazoa, as man, a distinctly inflammatory 
 but purely cellular reaction to injury is seen in non-vascular regions 
 such as the cornea. The reaction of the cornea to mild irritants 
 may sometimes be limited to a swelling and multiplication of the 
 corneal epithelium which replaces the cells destroyed b)' the irritant 
 without the intervention of wandering cells or tlie appearance of 
 vascular changes. With more active lesions, hofl-evor, manv wander- 
 ing cells gather through the lymph spaces to the site of the injury 
 where they, remove foreign matter and protect the regenerating cor- 
 neal corpuscles. (Corneal vaccinia.) 
 
 The phenomena of reaction to injury thus far considered include 
 therefore (1) irritation and degeneration or loss of tissue cells, 
 (2) the accumulation of wandering cells, leucocytes, and (3) the 
 proliferation of fixed tissue cells. In all the more intense grades of 
 inflammation in vertebrates these same cellular changes are present 
 even to an increased extent, but their presence is usually obscured 
 l)y more prominent vascular disturbances. 
 
Inflammatory Reaction in Vascular Tissues. 
 
 (i) Very Slight Vascular Disturbance. Primary Union of 
 Incised Wounds. It is theoretically possible that the reaction from 
 and repair of a clean incision. of vascular tissue may be limited almost 
 entirely to the fixed cells of the tissue, and some experimentei-s claim 
 to have observed very pure illustrations of this fact. In ^ncli 
 cases the incision divides the cuticle, the connective tiss\K's, and 
 the small vessels. If the edges of such a wound be promptly apposed 
 the hemorrhage is slight, the ends of the vessels are promptly closed 
 by coagula, very few tissue cells are destroyed, and a slight fibrinous 
 coagulum glues the edges together, so that at the end <>f an liour 
 the wound appears closed and only a slight reddening about the 
 incision indicates the moderate hyperemia of the blood vessels. Into^ 
 the coagulum the irritated connective tissue cells send long processes, 
 and new cells appear by multiplication of the old. The edges of the 
 wound become more firmly united by the new cells and processes. 
 The coagulum itself becomes condensed and fibrillated, piesenting 
 the characters of young connective tissue after the lapse of forty-eight 
 hours. IST'cAV capillaries are formed by the Inidding of endothelial 
 cells of adjoining vessels. Throughout the process very little exuda- 
 tion from the blood vessels and very few leucocytes are observed in 
 sections of the tissues, and the process is almost entirely limited to 
 the fixed cells of the part. The most successful cases of primary 
 union, by immediate cohesion, of surgical wounds follow some such, 
 course of repair, but in the vast majority of instances, even of rapid 
 primary union, sections through the line of incision will show some 
 dead tissue cells, a considerable number of leucocytes, and some exu- 
 dation from the blood vessels. 
 
 (2) Marked Vascular Reaction. Secondary Union. Exu- 
 dative Inflammation. The more extensive vascular changes which 
 characterize inflammatory reaction have been most completely studied 
 in clean wounds 01 the web of the frog's foot. The injury causes 
 first a dilatation and increased flow of blood in the vessels of the 
 part which becomes reddened and congested. Then follows a stage 
 of slowing of the blood current and certain changes in the blood cells 
 and plasma. 
 
 The leucocytes increase in number, they gather along the walls 
 of the vessels, adhere to the swollen sticky endothelium, and by virtue 
 of their amoeboid properties they pass through the vessel wall into 
 
13 
 
 the surrounding tissues and especially to the surface of the wound. 
 This process is called emigration of leucocytes. Through the open- 
 ings made by the white cells or more often through ruptures in the 
 endothelial wall, aided by increased blood pressure, red cells also pass 
 out of the vessels, the process being called diapedesis of red cells. 
 
 Exudation of blood serum accompanies or precedes emigration 
 and diapedesis. Through the swollen and more permeable endothel- 
 ial cells the fluids of the blood, under increased pressure, are forced 
 through the vessel walls to infiltrate the tissues or appear on the 
 surface of the wotind. 
 
 All three above processes tend to obscure the purely cellular re- 
 action which is nevertheless present and becomes apparent in the 
 process of repair. After- the vascular disturbance has somewhat sub- 
 sided the proliferation of connective tissue cells, the budding of new 
 caJDillaries, and the condensation of the new intercelldlar substance 
 may be seen in sections of wounds M'hich are undergoing repair. 
 
 The above course of events is seen in surgical wounds which 
 heal by secondary union, hi whicli the abundant exudate prevents im- 
 mediate cohesion of the divided surfaces, and healing begins only after 
 the exudation has partly subsided, and usually progresses from the 
 bottom of the wound upward. 
 
 In some cases in which exudation rapidly subsides, sccnndari/ 
 cohesion of divided surfaces may occur and healing follows after a 
 variable period as in primary union. If the cut surfaces are long 
 held apart no cohesion can occur, and healing takes place by a slower 
 process called granulation, which is best seen after suppurative in- 
 flammation. 
 
 (3) Intense Vascular Reaction. Suppurative Inflamma- 
 tion. Healing by Granulation. Wlien pyogenic microorganisms 
 are carried into a wound and infection occurs, a more intense grade 
 of inflammation is excited which is marked by abundant emigration 
 of leucocytes and copious discharge of pus. This process, called 
 suppurative inflammation, is best followed in tissues into wliicli 
 cultures of pyogenic cocci have been injected experimentally. Within 
 four hours after such injectiriu the vessels in the neighborhood are 
 gorged M'ith blood, the blood current slowed, and leucocytes increased 
 in nu]nber and adherent to the vessel walls. Such a condition is 
 termed acute congestion. 
 
 After ten or twelve hours increasing numbers of leucocytes have 
 
14 
 
 emigrated from the vessels until the tissue is thickly infiltrated by 
 these wandering cells, while diapedesis of red cells occurs in greater 
 or less degi-ee, and exudation of serum is in some cases a prominent 
 feature. 
 
 Although the exudation may be very abundant and the tissues 
 distended by leucocytes and blood cells, resolution may follow without 
 permanent damage to the tissue. If the bacteria are not too numerous 
 or virulent they are destroyed by the leucocytes and serum, after 
 A\-hich the inflammation slowly subsides. 
 
 Healing of simple suppurative inflammations takes place by 
 absorption of the fluid exudate and the fluidification, largely by 
 leucoeytic ferments, and absorption, of the cellular exudate. 
 
 When suppuration occurs in surgical wounds, all attempt at 
 cohesion of surfaces commonly fails and the wound is closed from 
 the bottom up by a slow process called healing by granulation. 
 Here, after partial subsidence of the exudation, new capillaries, form- 
 ing minute projecting tufts supported liy new connective tissue cells 
 with a little intercellular substance and many wandering cells, de- 
 velop on the cut surface forming what is known as grannJ/rtion iissue. 
 Such tissue has a granular looking surface owing to the projecting 
 tufts of vessels. This tissue fills up the wound, draws the surfaces to- 
 gether, and by gradual increase in the quantity and density of the 
 intercellular substance, disappearance of cells, and obliteration of 
 vessels, the tissue is transformed into dense connective tissue forming 
 a scar or cicatrix. Epithelium finally covers the wound by oradual 
 proliferation from the cut edges. 
 
 (4) Inflammatory Reaction with Local Death of Tissue, 
 Necrotic Inflammation. When bacterial inflammation reaches a 
 slipiDurative grade in a confined tissue it seldom resolves without 
 causing some death of tissue and forming an abscess. The additional 
 element of death of tissue throws the process into the class of necrotic 
 inflammation. 
 
 In the formation of an ab.-cess, the affected tissue becomes so 
 thickly infiltrated with leucocytes and so much distended by exuded 
 fluids that the vessels are compressed and the circulation obstructed. 
 All tissue cells thus cut o£E from nourishment promptly undergo acute 
 necrosis and become more or less fluidified. In some cases death and 
 fluidification occur apparently before there is sufficient exudate to 
 compress the vessels and the death of tissue is then referable princi- 
 pally to the necrotic action of bacterial poisons. 
 
15 
 
 Sections through an abscess disclose a central cavity filled with 
 pus and cellular detritus, an intermediate zone of intense purulent 
 infiltration, and a peripheral zone of congestion. Microorganisms may 
 be found especially in the fluid area, partly englobed in leucocytes, 
 partly in tissue spaces. In the early stage of the lesion they may be 
 present in all parts of the abscess wall even to the edges of the con- 
 gested area, but with the fluidification of tissue bacteria usually be- 
 gin to diminish, gradually succumbing to bactericidal agents, and 
 in quiescent abscesses of some duration the pus is frequently sterile. 
 
 Healing of an abscess is facilitated by evacuation of the contents 
 and approximation of the walls. The irritant being removed and 
 the pressure relieved, the vascular disturbance may rapidly subside, 
 exudation decreases, proliferation of connective tissue cells and blood 
 vessels progresses, and healing occurs as after a simple suppurative 
 inflammation, with the development of granulation tissue. A form 
 of secondary cohesion of the abscess walls may be secured which 
 greatly diminishes the space to be filled by granidation tissue. All 
 dead tissue is replaced, not in its original type but invariably l)y 
 granulation tissue and its final product cicatricial tissue. 
 
 (5) Inflammatory Reaction with Diffuse Death of Tissue. 
 Diphtheritic Inflammation. 
 
 Some intense chemical irritants and some bacteria, notably the 
 bacillus of diphtheria, when acting upon mucous membranes excite 
 an intense grade of inflammation characterized by considerable 
 fibrinous and purulent exudation and rapid death of superficial tis- 
 sues. The coagulated fibrin entangling the elements of necrotic tissue 
 and exudate tends to form a false membrane adherent to the surface 
 of the inflamed part, whence the term p^seuclo-memliraiious inflama- 
 iioii is applied to the process. Some forms of spreading suppurative 
 inflammation of deeper parts cause rapid death of considerable areas of 
 tissue, and much fibrinous exudate, and the term "diplitlieritic" 
 applies to this process also. (Diphtheritic erysipelas.) Healing 
 follows the same course as in simple necrotic inflammation. 
 
 (6) Gangrenous Inflammation. In some forms of virulent 
 and specific bacterial infection necrosis occurs rapidly and aft'ects 
 considerable areas producing death of tissue en masse. This tvpe of 
 inflammation is called "gangrenous." Some of the bacteria associated 
 •with gangrenous inflammation are anaerobic, produce gas, and cause 
 extensive decomposition and emphysema of the dead tissue. Gan- 
 
-1 6 
 
 grenous inflammation is thert^fore usua.lly characterized by death of 
 tissue "en massu." emphysema, and the emanation of foul odors. 
 Peculiar local or general predisposing factors are frequently present 
 to account for the violent course of gangrenous inflammation, as in 
 diabetes, but sucli factors are apparently not ah\a\-s necessary. Highly 
 poisonous end-products of proteid decomposition are developed in 
 gangrenous tissue which are lacking in chemotactic attraction for 
 leucocytes and wliich by absorption produce severe constitutional 
 disturbance. 
 
 Death of tissue "en masse'' but without much putrefactive change 
 occurs as a result of prolonged cold, {rhilblains), heat, pressure. 
 (bedsores), ergot poisoning, and disease of the nervous system 
 (syringo-mi/cUa) . The necrosis is here the I'osult of meclianical com- 
 pression of blood vessels with anemia, or of the peculiar effects of 
 heat and cold, or of disturbance of innervation, wliile the ordinary 
 features of a severe exudative or necrotic inflammation are wanting. 
 In such cases the dead tissue may dessicate and become mummified 
 (dry gangrene), or piitref action may supervene, ■wlien the process 
 is called moist gangrene. 
 
 In elderly subjects a form of dry gangrene in\olving whole 
 members (toes, feet, etc.), occurs from the occlusion of peripheral 
 arteries, and is called senile gangrene. 
 
 While a definite distinction must be drawn between simple gan- 
 grene, which is a form of necrosis from infarction, and gangrenous 
 inflammation, there are many gradations Ijctween these two extremes. 
 
 (7) Invasion of the Blood Stream by Bacteria. In all the 
 
 bacterial inflammations thus far considered the bacteria are confined 
 more or less completely to the site of the local lesion and none or very 
 few reach the general circulation. In a considerable proportion of 
 severe local infections and in some mild lesions (pannritknn) bacteria 
 have been found by culture in the circulating blood. It is probable 
 that in most of these cases the bacteria in the blood are comparatively 
 few in number, their presence is not constant, and they do not multiply 
 in the circulation to any definite extent, and hence do not produce 
 any marked constitutional disturbance. Such a condition may be 
 called bacteremia. 
 
 In some specific diseases {typhoid fever, pneumonia) and in many 
 very virulent local infections in susceptible individuals, bacteria are 
 present in the general circulation from the first or very soon gain 
 
'7 
 
 access to it, they multiply in the blood, are constantly demonstrable by 
 culture, and produce constitutional symptoms which are not satis- 
 factoril)- explained by the extent of the local lesions. This condition 
 is called septicemia. 
 
 It is evident that there are all gradations between a transitory 
 bacteremia and a progressive septicemia, and it is not always possible 
 to determine whether bacteria in the blood are multiplying or not, 
 hence the terms bacteremia and septicemia must be used to some 
 extent synonymously. 
 
 In some cases of bacterial invasion of the blood the micro- 
 organisms are carried b)' the blood current to distant tissues in which 
 they lodge and give rise to local inetastatic al)scesses, a condition 
 called pyemia. In cases of pyemia cultures of th« blood are usually 
 negative until shortly before death. 
 
 In some cases there are symptoms of profound intoxication by 
 bacterial and tissue products as -well as the development of meta- 
 static abscesses and this condition is sometimes called septicopyemia. 
 
 Pyemia nearly always arises from a suppurative inflammation 
 involving a vein, through which detached masses of blood clot and 
 Ijacteria are carried to distant tissues. The microorganisms con- 
 cerned are usually the ordinar)- bacteria of suppuration. {Staplii/lo- 
 coccus pyogenes.) 
 
 In Iwth septicemia and pyemia the microorganisms are multiply- 
 ing within the tissues. When bacteria Avhich are not capable of 
 multiplying within the living tissues, chiefly putrefactive species, 
 develop in dead tissues or in putrescible contents of cavities or cysts, 
 a severe form of intoxication arises which is known as sapremia. 
 (Retained secundines.) As there is no infection necessarily con- 
 cerned in such eases prompt recovery may ensue upon the removal 
 of the material from which the chemical poisons are being absorbed. 
 There are doubtless numerous combinations of, and transitions 
 between septicemia, pyemia, and sapremia. 
 
 Resume: In the preceding sketch of the different grades of re- 
 action to injury it has been shown that the inflammatory process 
 may consist in : 
 
 (1) A reaction limited entirely to the fixed cells of the tissue. 
 
 (2) A cellular reaction with congestion of the vessels. 
 
 (3) Cellular reaction and congestion, to which is added exuda- 
 tion of blood cells and serum. 
 
(4) Cellular reaction may be delayed or obscured and the exuda- 
 tion may be very prominent and consist largely of leucocytes 
 (suppurative inflammation). 
 
 (5) To the suppurative process may be added death of tissue and 
 abscess formation (necrotic inflammation). 
 
 (6) Necrosis of tissue may be rapid, superficial, and diffuse, 
 with or without formation of pseudomembrancs (diphtheritic 
 inflammation). 
 
 (7) Kecrosis of large areas of tissue "en masse" with decompo- 
 sition of the dead tissue may be a striking feature (gangrenous in- 
 flammation) . 
 
 (8) The local reaction may be slight and inadequate to check 
 the entrance of bacteria into the blood stream in wliich they multiply 
 and produce severe general systematic disturbance (septiceuiia, bac- 
 teremia) . 
 
 THE SEPARATE FACTORS IN 
 INFLAMMATION 
 
 Thus far have been indicated the general phenomena which occur 
 in different grades of acute inflammation. The reaction to injury 
 however is not always acute and progressive. The changes may be 
 chronic and may not pass beyond the stage of degeneration or may 
 consist chiefly of regeneration. 
 
 In such cases the process involved may present exaggei-atcd phases 
 not seen in the acute progressive inflammatory reaction. It becomes 
 necessary therefore to consider in greater detail and in wider scope 
 the separate factors of inflammatory reaction. 
 
 The Vascular Changes. 
 
 Thrombosis, Embolism. Infarction. 
 
 The formation of clots in a vessel is called thrombosis. Throm- 
 bosis occurs in small vessels as a result of the stasis caused 
 by acute inflammation of their walls, or by compression. Marasmic 
 thrombi develop in large veins in individuals with en- 
 feebled circulation or anemic blood. Changes in the blood itself may 
 
19 
 
 strongly predispose to thrombosis or may alone give rise to -extensive 
 thrombi. In the course of infectious diseases the increase of fibrin 
 and the excess of leucocytes are the chief factors in the formation of 
 thrombi (pneumonia), while poisoning by blood solvents, or the 
 presence of any hemolytic agent, may lead to destruction of many red 
 cells and the formation of thrombi composed of their detritus. 
 
 The formation of a thrombus in a large vessel usually begins 
 with the cohesion of leucocytes or blood plates to the endothelium. 
 Usually the endothelium is previously altered, thereby losing its in- 
 hibiting influence over coagulation, but thrombosis may begin before 
 any changes are demonstrable in the endothelium. By gradual 
 accretion of blood plates, leucocytes, and fibrin, white parietal 
 tJiroinbi of considerable dimensions may arise. Any one of these three 
 elements may be in excess but usually all are present. 
 
 In most cases the enlarging thrombus entangles red cells from 
 the blood current producing mixed thrombi, or blood plates, leuco- 
 cytes and fibrin may form layers alternating with red cells (lamellated 
 thrombus) , or considerable quantities of blood may be involved giving 
 large red thrombi. 
 
 When the coagulation of the blood itself once begins it is apt to 
 extend over considerable areas, in fact the entire inferior vena cava 
 has been found thrombosed. In the veins large thrombi may become 
 loosened and failing to pass the valves may become condensed and 
 finally calcified producing movable phleboliths. Similar masses form 
 in the heart. 
 
 In the smaller vessels blood plates become fused togethet into 
 white hyaline masses, and the red cells become agglutinated and fused, 
 forming hyaline thrombi. 
 
 Sections of thrombi present microscopically the elements men- 
 tioned in varying combinations. The blood plates are granular or 
 hyaline, the fibrin may appear as fibrils radiating from leucocytes or 
 blood plates and entangling red cells, or as hyaline masses. 
 
 The red cells usually show degenerative changes. (1) They may 
 be subdivided into small fragments (microcytes) containing 
 hemoglobin. (2) They discharge masses of blood-plates containing 
 their nuclear material, and from these plates the formation of fibrin 
 begins. (3) They may be fused together into large homogeneous 
 masses called agglutination thrombi. (4) Their dissolved hemoglo- 
 
20 
 
 bin may crystallize in the form of grannies or rhombic plates of 
 hemoglobin or hematoidin. 
 
 The factors determining the coagulation of the blood are prob- 
 ably globulins from the red cells and plasma, ferments derived from 
 the red cells and leucocytes, and calcium salts from the plasma. 
 
 The fate of thrombi depends on their character and the conditions 
 under which they form. In large vessels the most favorable outcome is 
 organization by vascular connecti^'e tissue growing from the intima. 
 By this process the thrombus is replaced by connective tissue which 
 gradually contracts, permanently occluding the vessel. Or the throm- 
 bus may soften in the centre ^\'hile organizing elsewhere and a new 
 channel may form restoring the lumen of the vessel. Suppuration 
 complicates thrombosis in many cases of phlebitis giving rise to 
 septic emboli ov to rupture, and calcitication occurs in some old 
 thrombi. 
 
 The diverse etiology and morphology of. thrombosis may be 
 summarized as follows : 
 
 Etiology. (1) Changes in the vessel walls. Inflammation. De- 
 generation of endothelium. (2) Changes in the blood. I'erment 
 thrombosis in infectious diseases with hyperinosis and leucocytosis 
 (Pneumonia.) Action of hemolytic agents. Marasmic {anemic) 
 thrombosis. (3) Changes in the circulation. Marasmic thrombus. 
 Thrombosis from compression, ligature. Stasis. 
 
 Morphology. (1) ^y]lite thrombus. Blood plates, leucocytes, 
 fibrin. (2) Red thrombus. Coagulation involving whole blood. 
 (3) Mixed thrombus. Combinations of leucocytes, blood plates, and 
 fibrin, with red cells, forming during irregularities of the circulation 
 or with suppuration. (4) Hyaline thrombi of platelets, red cells, or 
 fibrin, usually in small vessels. (5) Miscellaneous varieties, such as 
 farietal polypoid, valvular, occluding thrombi, ball thrombi loose in 
 heart, phleboliths recent, loose, or calcified, in the large veins. 
 
 Embolism. When a foreign body or any mass formed within 
 the body gains entrance to the blood or lymph vessels and is carried 
 by the circulation until it lodges in a vessel too small to permit its 
 passage, the process is called embolism, and the lodged body an 
 embolus. When bacteria or groups of tumor cells are disseminated 
 in the body in this way the process is called metastasis. 
 
21 
 
 Embolic masses may travel against the usual direction of the 
 current, producing retrograde metastases or embolism. This occurs 
 principallj' in lymph vessels, less often in blood vessels, and results 
 from irregularities in the circulation. Thus, clots from the right 
 heart may be lodged in peripheral veins and inhaled dust may pass 
 through the lymphatics back to abdominal nodes and spleen. 
 
 Emboli may consist of : ( 1 ) Detached portions of blood thrombi. 
 (2) Groups of tumor cells, producing metastatic tumors. (3) Tissue 
 cells; liver cells, after injuries of this organ; placental cells in 
 eclampsia or normal pregnancy; bone-marrow cells after fractures; 
 and clumps of leucocytes in the infectious diseases. (4) Bacteria 
 from local inflammatory foci, constituting the visual mode of origin 
 of metastatic inflammations. (Pi/einia.) (5) Pat. After crushing 
 injuries or concussion fluid fat from the bone-marrow or other in- 
 jured fat tissue may plug the vessels of internal organs, chiefly in the 
 lungs. (6) Air is sometimes aspirated through exposed large veins, 
 and acts as an embolus, interfering with the pulmonary circulation. 
 (7) Dust and other pigment particles are commonly carried by the 
 lymph or blood plasma or in leucocytes from their point of entrance 
 into the tissue and lodged in the nearest lymph nodes or capillaries, 
 as minute emboli. 
 
 Emboli, according to their character, produce obstruction of the 
 circulation and local necrosis, local inflammations, tumors, etc. If 
 very small their effects are unimportant, but if they obstruct larger 
 vessels the blood supply in a certain peripheral area may be cut off 
 and infarction results. 
 
 Infarction. When the circulation in an artery is suddenly cut 
 off by thrombosis, embolisn>, or other occlusion, the wedge-shaped 
 area of distribution of the occluded artery dies, the process is called 
 infarction and the affected area an infarct. 
 
 (1) When the occluded vessel possesses no lateral anastomoses 
 (terminal artery), the infarcted area usually contains little blood and 
 is light colored. (Anemic or white infarct.) 
 
 (2) When moderate collateral anastomosis exists, blood gathers 
 in the infarcted area either through the anastomosing vessels or by 
 retrograde flow through the veins, the tissue becomes distended with 
 blood which cannot move onward but soon passes through the asphyx- 
 iated vessel walls by diapedesis, and the condition of red or hemor- 
 rhagic infarction is established. Even with terminal arteries (brain) 
 
22 
 
 hemorrhagic infaets may arise by backward ilow of blood through 
 the veins. 
 
 (3) When collateral circulation is very rich, as in the lung,, 
 embolism ia followed by infarction only when there exists some other 
 obstruction to the venous circulation, as heart disease, or emphysema, 
 and when it occurs is always hemorrhagic. 
 
 Hemorrhagic infarcts occur chiefly in the lungs, in the region 
 of distribution of the superior mesenteric artery, and in other organs 
 occasionally, when there is passive venous congestion. 
 
 Infarcted tissue usually dies within a few hours. The tissue 
 undergoes simple or coagulation necrosis, the necrotic mass excites 
 an exudative inflammation, and its periphery is infiltrated with 
 leucocytes. Finally the dead area is partly absorbed and then 
 replaced by connective tissue. 
 
 Exudation, Diapedesis, Emigration. 
 
 Cohnheim first fully described the vascular changes which occur 
 in the exposed frog's mesentery, or in the frog's tongue from which 
 the papillae were removed by a clean incision. The exposed vessels- 
 first show a gradual dilatation, most marked in the arteries, then 
 in the veins, and least of all in the capillaries. At the same time 
 there is an acceleration of the blood current, again most prominent 
 in the arteries but visible also in the veins and capillaries. This 
 acceleration seldom lasts more than an hour and in the tongue may 
 be absent entirely, and is succeeded by a retardation of the blood 
 stream in the vessels which may be doubled in capacity. There is- 
 thus established a condition of partial stasis in which the state of 
 the arterioles, capillaries, and veins, is as follows : 
 
 In the veins the lighter and sticky leucocytes gather at the peri- 
 phery of the blood stream and eventually adhere to the endothelial 
 cells in a continuous resting layer, while the slowly-moving central 
 current is occupied by red cells and plasma. The axial stream of 
 red cells seen in normal circulation is missing and the plasma and 
 red cells are uniformly mingled. At first the systolic pulsation is 
 visible but this gradually fails when the stasis becomes complete. 
 The capillaries are moderately distended but the endothelial cells- 
 are lined by an admixture of leucocytes and red cells and not exclu- 
 sively by leucocytes as in the veins. In the arterioles the leucocytes- 
 tend to gather at the periphery but are commonly swept onward bv 
 the systole of the heart, and do not remain fixed. 
 
23 
 
 "When the circulation reaches this condition of partial stasis the 
 elements of the blood begin to pass out of the vessels. This process 
 includes: (1) Exudation of blood plasma. (2) Diapedesis of red 
 •cells. (3) Emigration of leucocytes. 
 
 Exudation. The passage of blood serum out of the vessels, 
 which is the cardinal feature of exudative inflammation, is largely 
 dependent upon stasis in the vessels in inflamed tissues. The chief 
 factors concerned are : ( 1 ) Increased blood pressure in the distended 
 small vessels. (2) Changes in the endothelial cells. Owing to lack 
 of nutrition and to the degenerative effects of the irritant the endo- 
 thelial cells become swoollen, more permeable, and the stomata be- 
 tween them become wider. (3) Alteration in the composition of 
 the blood. Watery plasma containing diminished proteids exudes 
 more readily than normal plasma. (4) Changes in the osmotic 
 relations of the blood and tissue fluids. (5) A secretory action of 
 the endothelial cells is apparent in some inflammations in which very 
 large quantities of serum are exuded and probably also in other types 
 of inflammation. 
 
 The exact influence of these various factors in different forms 
 ■of exudation has not been fully determined. It is doubtful if in- 
 creased pressure alone is ever capable of causing exudation, and 
 changes in the endothelial cells are probably always necessary. JSTor 
 has it been satisfactorily shown that the purely physical factors, 
 pressure, dialysis, and osmosis, are sufficient to account for any form 
 of exudation. 
 
 Tissues infiltrated by fluid exudates are said to be edematous, 
 and in a state of edema. Owing to the varying prominence of the 
 different causative factors the quality of the exudate varies. When 
 increased blood pressure is the chief factor, as in chronic valvular 
 disease of the heart, the discharged fluid contains only a small pro- 
 portion of the more readily diffusible proteid of the blood, serum 
 albumen. This condition is called passive edema, and the fluid a 
 iransudate. 
 
 The edema of anemia, cachexia, and nephritis, is largely a pas- 
 sive process in which chronic stasis and changes in the blood are 
 concerned. When an active inflammatory process exists the exudate 
 usually shows a higher proportion of the less diffusible blood albu- 
 men, serum globulin, the' presence of which indicates a more serious 
 alteration of the vessel wall. 
 
24 
 
 Some forms of inflammation, especially those caused by the pneu- 
 mococcus, are characterized by the exudation of much iibrinogen 
 which soon coagulates yielding a fibrinous deposit. Fibrinous exu- 
 dates usually contain leucocytes which supply the fibrin-ferment, but 
 an excessive number of leucocytes, as in pus, prevents coagulation, 
 possibly from the action of anti-ferments. 
 
 Exuded fluids distend the tissue spaces, separate and rupture 
 tissue cells and fibres, infiltrate tissvie cells, and compress the vessels. 
 
 Extensive edema however may be resolved by an increased flow 
 of lymph, which usually passes from inflamed and edematous tissues, 
 and by discharge from surfaces and into cavities. Moderate fibrinous 
 exudates mixed with leucocytes are dissolved by leucocytic ferments 
 but when the fibrin is excessive and leucocytes deficient, it persists 
 long in the tissues or on surfaces and may become organized. {ThicTc 
 fibrinous pleurmj. Organizing pneumonia.) 
 
 Diapedesis of Red Cells. The passage of red cells through the 
 vessels is a prominent feature of some exudative inflammations. In 
 the mildest cases red cells pass out chiefly from the capillaries where 
 both red and colorless cells lie in contact with the endothelium dur- 
 ing stasis. As the erythrocytes are not amoeboid this transit is a 
 purely passive phenomenon resulting from increased pressure and 
 loss of continuity of the vessel -wall. 
 
 Xumerous factors determine the extent of diapedesis. Very 
 vascular tissues frequently yield hemorrhagic exudates from lesions 
 of moderate intensity. {Pneumonia in infants.) Certain patho- 
 genic bacteria have a special tendency to excite hemorrhage, as a 
 result of destruction of endothelial cells and the rupture of capil- 
 laries. (BariUns coli communis, Bac. tuhrrculo.'iis, Streptococcus.) 
 As a rule bloody exudates indicate an intense form of bacterial infec- 
 tion. The loss of blood is most abundant in the early stages of such 
 ])rncesses. while after many leucocytes have gathered at the focus 
 diapedesis is less abundant. The state of nutrition of the tissues 
 is an important factor in many cases, while in the hemorrhagic 
 diathesis there is a constitutional predisposition toward hemorrhages 
 which occur from slight trauma or ordinary bacterial infections, and 
 which is probably due to anomalies in the structure of the vessels 
 and to deficiency in the coagulability of the blood. 
 
 Exudates containing blood are called sanguinolent, or if m'ixed 
 with serum, sero-sangvinolent, etc. Extravascular red cells con- 
 tribute to the swelling of inflamed tissues. They gradually disinte- 
 
25 
 
 grate under the action of hemolytic agents in the tissues and yield 
 various pigments, hematoidin, hemosiderin, and other derivatives 
 of hemoglobin. These changes give rise to the varying colors of 
 bruises, while the last trace of marked hemorrhage in a tissue is 
 seen microscopjeally in the presence of brownish pigmented phago- 
 cytes. 
 
 Emigration of Leucocytes. Emigration of leiicocytes may 
 begin very early during the course of vascular changes, but it usu- 
 ally follows exudation of serum and except in very severe iniiamma- 
 tions precedes diapedesis. By means of their amoeboid properties 
 and in response to chemotactic influences the leucocytes, chiefly the 
 pol3Tiu.clear cells which have become attached to the vessel wall, 
 begin to extrude pseudopodia through or between the swoolen endo- 
 thelial cells, gradually traverse the wall, and finally lie free in 
 the tissue spaces. At first they tend to gather in layers ' about the 
 vessels from which they have escaped, but later they lie in large 
 numbers diffusely in the tissue spaces, or migrate to the surface of 
 mucous membranes or wounds. 
 
 Two essential conditions for emigration are the maintenance 
 of the circulation and the adherence of leucocytes to the vessel 
 wall. (Cohnheim.) Emigration ceases when there is complete 
 stasis and leucocytes do not emigrate through the larger arterioles. 
 All varieties of leucocytes have the po^ver of emigration, but as will 
 be shown later, different cells respond chiefly to different chemotactic 
 influences. The fate of emigrated leucocytes varies with the t3'pe, 
 location, and intensity of the inflammation. The majority of them 
 mingle with scrum and form pus. In mild inflammations, upon 
 resolution, some leucocytes may wander back into the blood vessels, 
 or be carried off hy lymph vessels. Others undergo autolj'sis (self- 
 digestion), and their fluid products are absorbed. Some are also 
 digested l)y pliagocytic cells. Mononuclear cells may be permanently 
 but passively incorporated in growing connective tissue. Mononu- 
 clear and onsinnpliile cells may multiply after emigration, but poly- 
 nuclear neutrophile cells probably do not possess this capacity. 
 
 Leucocytosis and Its Significance. The importance of wan- 
 dering cells in the reaction to irritants has been clearly shown in 
 the lower raetazoa in their behavior toward foreign bodies which 
 they englobc and digest or excrete. In the higher animals the wan- 
 dering cells or "leucocytes are greatly increased in number in inflam- 
 
26 
 
 mation, and this increase, which afiEects chiefly the polvnuclear 
 neutrophile cells, is called, leucocytosis. More specific terms are 
 polynuclear leucocytosis, eosinophils leucocytosis or eosinophiha, and 
 mononuclear leucocytosis or lymphocytosis. 
 
 In most bacterial infections the leucocytes are increased in num- 
 ber not only in the inilamed tissue but in the general circulation 
 as well, and in their places of origin, the lymphoid tissues, pronounced 
 evidence of increased formation of leucocytes has been found to 
 accompany distant suppurative inflammations. We therefore dis- 
 tinguish (1) a local and (2) a general or intravascular leucocytosis. 
 In nearly all forms of exudative inflammation, especially in the 
 suppurative type of bacterial origin the leucocytes have an important 
 function to fulfll. In the early stages of the process the congested 
 vessels are usually found to contain an excess of these cells which 
 have been attracted to the locality by the positive chemotactic influ- 
 ence of bacteria and their products. N"egative chemotaxis, or a 
 repelling force of bacteria upon leucocytes, seems to exist in the early 
 stages of many severe bacterial infections, and may be held responsi- 
 ble for the diminished number of leucocytes in the local focus and 
 in the general circulation (hypoleucocytosis) which sometimes pre- 
 cedes their increase. 
 
 The mechanical sifting of cohesive leucocytes by swollen sticky 
 endothelium may contribute partly to the local gathering of leuco- 
 cytes. Yet it has been shown that all the local changes in the blood- 
 vessels may exist without any local afiiux of leucocytes; that the 
 leucocytes will overcome considerable obstacles in order to reach 
 the bacteria, crowding into smooth glass tubes containing bacteria; 
 wliile Lebert has shown that a positive chemotaxis is exerted upon 
 leucocytes in distant blood vessels when the non-vascular cornea is 
 inflamed. 
 
 It is chiefly as a means of defense of the animal organism 
 against bacterial invasion that leucocytosis exhibits most clearly its 
 teleological significance. If sections are made of tissues one hour 
 after the subcutaneous injection into a raljliit of bar. pynn/aneus the 
 area surrounding the bacteria is found to be anemic, while the leu- 
 cocytes are prer-ent in scanty number, having apparently been repelled 
 by .the bacteria. This period corresponds to a stage of negative 
 chemotaxis which occurs at the beginning of most infectious diseases, 
 continuing till death in some virulent infections in susceptible ani- 
 mals, and persisting only a few minutes or hours in milder infections 
 
27 
 
 or in refractory subjects. It is often attended by a diminution of 
 leucocytes throughout the circulation {liypoleucocytosis) , these cells 
 being lodged in the visceral capillaries. 
 
 If the sections are made several hours after the injection, the 
 leucocytes are found to have gathered in large numbers at the site 
 of inocul-ation. Many white cells may be destroyed by the bacteria 
 and their products, but others are seen to have englobed the bacilli 
 which may be recognized in various stages of digestion. When first 
 englobed they retain their normal staining reaction with methylene 
 blue, but during digestion they lose their affinity for methylene blue, 
 stain only with eosin, and finally break up into acidophile granules 
 and disappear. Under favorable circumstances the leucocytes suc- 
 ceed in engiobing and destroying all the bacteria, after which heal- 
 ing occurs as with aseptic wounds. 
 
 There are great variations in the phagocytic power exhibited by 
 leucocytes of different animals toward pathogenic bacteria and this 
 power is greatly increased in artificial immunization. When virulent 
 diphtheria bacilli are inoculated into the eye of a rabbit, an advancing 
 necrotic inflammation follows which destroys the eye and may kill 
 the animal. During this process a thin bloody discharge is exuded 
 containing few leucocytes, and in the tissue few leucocytes appear 
 and there is little phagocytosis. When a similar inoculation is per- 
 formed in an animal which has previously received several immuniz- 
 ing injections of diphtheria antitoxin, a rich purulent exudate soon 
 appears, the leucocytes englobe and destroy tlie bacilli, the inflamma- 
 tion is limited to the eye-ball, and the animal recovers. 
 
 Leucocytes are not the only elements in the body which exert 
 bactericidal and phagocytic properties in inflammation. Blood 
 serum, lymph, and mucus, exhibit varying degrees of this activity, 
 while endothelial, epithelial, visceral, and connective tissue cells all 
 enjoy more or less phagocytic power. 
 
 The extra-cellular destruction of bacteria by body fluids was first 
 demonstrated by Pfeiffer, who found that cholera bacilli injected into 
 the peritoneal cavity of a highly immunized animal were dissolved 
 and destroyed without the intervention of phagocytic cells. This 
 observation is known as the phenomenon of Pfeiffer. It has since 
 been rendered probable that in the phenomenon of Pfeiffer one of 
 the agents essential to the destruction of bacteria by the peritoneal 
 and other fluids is furnished chiefly by the leucocytes. 
 
 The most intimate knowledge of the mode of destruction of 
 
28 
 
 bacteria in tlie body has been furnished by the studies of Ehrlich, 
 Bordet, and others. It has been shown that bacteriolysis is the result 
 of the combined action of two principles: the immune body or ambo- 
 ceptor, and the complement. 
 
 The thermostable iiniaune body, or amboceptor, is developed 
 during the course of infection of susceptible animals. It consists 
 of, or is inherent in, certain proteid molecules which are thrown off 
 as a secretion from the cells chiefly attacked by the bacteria, and it 
 has a specific chemical affinity for the proteid molecules of the cor- 
 responding bacterium. Its function is to bind to the bacterium or 
 foreign cell the destructive agent which is the complement. 
 
 The compleinml is a ferment inherent in proteid molecules which 
 are normally present in the leucocytes and probably in other cells, 
 and which are discharged from these cells at their dissolution. It is 
 thermolabile and is destroyed by heating for one hour at 56° C. 
 It has not been positively determined whether the complement exists 
 free in the plasma and lymph or only in the leucocytes. The com- 
 plement, being bound to the bacterium by the amboceptor, acts as 
 tlie destructi^•e agent. In phagoc3tos)s the bacteria have been loaded 
 with amboceptor and are then digested by the intracellular comple- 
 ments of the phagocytes. 
 
 It may safelv be said therefore that the leucocytes are one of 
 Nature's chief agents in limiting bacterial infections, while important 
 or sometimes essential aids in this function are furnished by tissue 
 cells and tissue fluids. Since the state of nutrition and metabolism 
 of the blood and tissues de])en(ls largely upon the activity of the 
 organs, it A\'ould appear that immunity against bacteria is ultimately 
 a function of the organs. Local L^ucocytosis signifies Nature's effort 
 to limit the s])read of bacterial infection, while the intravascular 
 leucocytosis measures the same effort to furnish leucoc3'tes at the 
 point of invasion and to rid the blood and system of bacteria and 
 their products. 
 
 Mononuclear Cells in Inflammation. In some forms of in- 
 flammation, especially of the subacute or chronic ty])e, many mononu- 
 clear cells are present in tlie inflamed tissues. In some eases these 
 cells are typical small lymphocytes and there is no good reason to 
 doubt that they have emigrated from the blood vessels in response 
 to chemotactic attraction, since amoeboid motion and emigration from 
 the vessels have often been demonstrated for these cells. Inflamma- 
 tions whicli exhibit a special tendency to affect the Ij^mphatie system 
 
29 
 
 and spread through lymph vessels induce lesions in which many 
 Ijanphocytes are found. {Tuberculosis, typhoid fever.) In many 
 instances some or all of the new mononuclear cells are larger than 
 the small lymphocytes of the blood, possess a well-defined layer of 
 nearly homogeneous basophile protoplasm, and a single compact and 
 usually eccentric nucleus. These elements are termed plasma cells. 
 They are indistinguishable morphologically from large lymphocytes, 
 but their origin cannot in every case be determined with certainty, 
 iluch study has been devoted to these cells as a result of which it 
 is probable that large nononuclear cells may be derived (1) from 
 l3Txiphocytes of the circulation, or (2) from multiplying fibroblasts, 
 or (3) possibly from multiplying endothelial cells. 
 
 Inflammatory processes in which many mononuclear cells are 
 concerned are frequently followed by the growth of new connective 
 tissue. Careful study of the cells in such growing connecti^'c tissue 
 has shown that there are rather wide limits between which the forms 
 of fibroblasts and endothelial cells may vary, that they are often 
 indistinguishable from one another and from large and small lympho- 
 C3'tes. In view of this fact Maximow has suggested the term polyblast 
 for the large and small mononuclear cells of inflamed tissues. In 
 spite of the difficulty of distinguishing the true nature of these cells 
 there is no sufficient ground for supposing that the emigrated leu- 
 cocytes ever become transformed into fibroblasts although they may 
 become passively incorporated in the new tissue. 
 
 Eosinophile Cells in Inflammation. Some forms of inflam- 
 mation are attended l)y a local increase in the number of eosino- 
 phile leucocytes and often with a corresponding increase of these 
 cells in the general circulation. 
 
 Eosinophile cells are actively amoeboid and in response to 
 chemotactic influences emigrate from the vessels, but the chemical 
 substances possessing this influence are different from those which 
 affect other leucocytes. 
 
 Eosinophile cells are increased locally or in the blood in (1) many 
 acute exudative .processes toward the decline of the more active 
 inflammation when the neutrophile cells are diminishing (pneumonic 
 crisis), (2) in many suJjacute or chronic inflammations especially 
 of the skin {pemphigus) or mucous membranes {chronic hronchitis) . 
 (3) often in tissues which have been the seat of much hemorrhage, 
 and (4) in diseases due to animal paracites {trichinosis, filariasis, 
 intestinal parasitism). 
 
3° 
 
 A marked increase of eosinophile cells in the general circulation 
 usually accompanies the local afflux, as these cells are derived primarily 
 from the bone-marrow, although multiplying to some extent alter 
 lodgment in the altered tissues. Eosinophile cells are not phagocytic 
 but are believed by some to exert a protective action by the discharge 
 of a secretion which may be contained in their granules. Others 
 hold that these granules are derived by absorption of foreign sub- 
 stance. 
 
 Changes in the Tissue Cells in Inflammation. 
 
 Degeneration and Necrosis. The initial injury which leads 
 to inflammation always first affects the cells of a tissue causing dis- 
 turbance of the nutrition and metabolism of the cell followed by 
 certain morphological changes from which however the cell may 
 recover. This process is called degeneration. 
 
 Some cells coming into immediate contact with the injurious 
 agent or long exposed to its influence may suffer more serious dis- 
 turbance of its functions so that it undergoes extensive morphological 
 changes and dies. Such a process is called necrosis. 
 
 Degeneration. 
 
 The mode of origin or pathogenesis of the changes in degenera- 
 tion is very difficult to determine while the significance of these 
 changes is equally great. Some of the definite factors known to be 
 concerned in one case or another are : 
 
 ( 1 ) Disturbance of the nutrition of the cell. 
 
 (2) Accumulation of intracellular secretory products. 
 
 (3) Disturbance of the specific cell ferments. 
 
 (4) Autolysis, or digestion of the cell proteids by its own 
 ferments. 
 
 (5) Action of exogenous ferments. 
 
 (1) In ganglion cells there is a form of degeneration which 
 appears to be chiefly the result of loss of nutriment by the cell and 
 is characterized by diminution in size or disappearance of the normal 
 chromophilic bodies of the cytoplasm which represent reserve nutri- 
 ment of the cell. These chromophilic masses (Nissl's bodies) are 
 
31 
 
 diminished in size by prolonged physiological excitation of the cell, 
 but they are more quickly affected by diminution of the blood supply 
 of the tissue than by any other factor. 
 
 (2) In the liver cell acute degeneration frequently causes the 
 accumulation of bile pigments within the cell; or, in diabetes, of 
 glycogen. Both of these substances may alter the appearance of liver 
 cells and be mingled with other cytoplasmic elements in acute 
 degeneration. 
 
 (3) Disturbance of specific cell ferments. The life processes 
 of cells are now known to be the expression of the action of a series 
 of ferments which in various combinations are inherent in the proteid 
 molecules of the cell. The specific functions of visceral cells are 
 probably due in most instances to the action of such ferments. Thus 
 there are in the liver cells, urea-forming, glycolytic, and hemoglobin- 
 splitting ferments, besides oxydizing, hydrolyzing, lipolytic, and pro- 
 teolytic ferment actions shared by many other cells. These ferments 
 are both katalytic, breaking down complex molecules into simpler 
 ones, and synthetic, building up complex molecules from simpler 
 elements. It is an important fact also that at least some of these 
 ferments under certain conditions are reversible, e. g., the urea- 
 forming ferment may split up urea. 
 
 Any influence which disturbs the action of these cell ferments 
 would then alter the function of the cells and sooner or later their 
 morphology. In this way one may conceive of the accumulation 
 in the liver cell of glycogen, bile pigments, fat, or the constituents 
 of urea, or other of the chemical principles which are prominent in 
 different forms of degeneration, as glycogenic, fatty, etc. 
 
 (4) Autolysis. The conception of autolysis is bound up with 
 that of cell ferments. ISTearly all cells, especially those of the viscera, 
 and leucocytes, contain proteolytic and hydrolytic ferments which 
 under abnormal conditions act upon the cell proteids producing 
 albumose, amido-acids, and other proteid cleavage products, disturb- 
 ing the function and completely altering the appearance of the cell. 
 When organs removed from the body are kept aseptically under 
 toluol at room temperature they soon undergo autolysis from the 
 action of these ferments. The chemistry and morphology of cells 
 undergoing aseptic autolysis are so similar to the changes of acute 
 granular, hydropic, and fatty degeneration as to suggest that all of 
 these processes are of similar nature. 
 
32 
 
 The relation between disturbance of the specific cell ferments 
 and autolysis is theoretically not known, but experience indicates 
 that the former condition usually precedes and initiates the other. 
 In fact the functions of cells may be completely inhibited without any 
 signs of autolysis or other morphological change being demonstrable. 
 
 (5) Action of Exogenous Ferments. When bacteria are present 
 in inflamed tissues many of the degenerative changes in cells are 
 referable largely or in part to the acti(m of ferments emanating from 
 the bacterial cells. 
 
 Besides the specific toxins, bacteria contain hemolytic, proteo- 
 lytic, and oxidizing ferments which interfere with tlie function of 
 tissue cells and attack their protoplasm. The action of these bac- 
 terial ferments is doubtless the first step in the degenerative process 
 in tissue cells in bacterial inflammations, and both the degenerations 
 and the necroses of cells in the presence of bacteria are often more 
 or less specific. {Glamlcis.) The fluidification of tissue in abscesses 
 and in gangrene are pronounced examples of active proteolysis in 
 which bacterial ferments are ]ar<;ely concerned. 
 
 The chief varieties of degeneration affecting cells and tissues 
 are Granular, Hydropic, Fatty, Mucous, Glycogenic, and Hyaline. 
 
 Granular Degeneration. Cloudy Swelling. The particular 
 form taken by mild or early degenerative processes depends largely 
 on the structure of the cell, and a separate description of this process 
 is required for nearly every type of cell. 
 
 The typical condition known as gi-anular degeneration is seen 
 in the liver and kidney of acute infectious diseases, such as typhoid 
 fever or septicemia. The renal tubule cells in such a case are swollen, 
 the increase in size affecting both cell body and nucleus. The cell 
 body, instead of being translucent in the fresh condition, is more 
 opaque, and, instead of exhibiting a finely granular structure, is more 
 coarsely granular. These finer changes are not always maintained 
 in hardened tissues. Such alterations affecting all the cells of 
 the viscus, the kidney is increased in size, diminished in con- 
 sistence, and its minute naked-eye markings are rendered obscure. 
 The organ as examined by the naked eye is said to be in a state of 
 "cloudy swelling," and the cells as examined by the microscope in 
 a state of granular degeneration. Such cells are very apt to become 
 fragmented or loosened from their basement membrane, i. e., exfoliated. 
 
 Granular degeneration of much the same type affects most 
 glandular secreting cells, fibroblasts, and endothelium, and occurs in 
 
33 
 
 some portions of nearly all inflammatory foci, preceding other changes 
 of a more serious type. If the process goes no further such cells 
 commonly regain their function and are not destroyed. Though 
 usually acute, granular degeneration may occur as a chronic process. 
 
 Hydropic Degeneration. When inflamed tissues become in- 
 filtrated with much fluid, either from edema or from the fluidifying 
 action of CL'llular or bacterial ferments or chemical irritants, many 
 cells absorb the fluid or develop it within the cytoplasm and in sec- 
 tions appear to be distended by vacuoles. These vacuoles are less 
 spherical than those left by fat and usually contain granular detritus. 
 The remaining protoplasm is usually coarsely granular. Such cells 
 are very readily fragmented or exfoliated and destroyed. 
 
 Fatty Degeneration. In many conditions characterized by 
 anaemia or toxemia the cells of viscera and tissues contain a large 
 proportion of visible fat in the form of spherical globules. 
 
 The fats are triglycerates of stearic, palmitic, aud oleic acids and 
 with these are mingled margarates, ' cholesterin, and lecethiu. Osmic 
 acid, which is commonly used to demonstrate fat, stains black only the 
 oleates. Sudan III and Scharlach R stain other members of the trig- 
 lycerate series and lecethln, and by means of these stains the presence 
 of fatty substances in cells has been demonstrated to be much more 
 frequent than was formerly supposed. 
 
 The origin of the fat in fatty degeneration has never been fully 
 determined. Three theories to account for its presence are held : 
 
 (1) The fat represents tlie transformed proteid of the cell. 
 
 (2) The fat is a deposit in the cell from the circulating fat 
 derived from the normal fat depots and the food. 
 
 (3) The fat is derived from fat-like substances which are not 
 visible in normal cells, or it exists in the normal cell as an invisible 
 emulsion. 
 
 (1) It has long been supposed that in degenerating cells the 
 fat is derived from the transformed proteids of the cell (Virchow). 
 Yet the amount of fat in the livers of very obese subjects or of 
 chronic alcoholics may considerably exceed the normal bulk of the 
 liver, and hence such fat must be to some extent a deposit from the. 
 blood. It has not been found possible to transform proteid into fat 
 in the test tube, but the increased output of urea in phosphorus, 
 poisoning is strong evidence that the fat in this condition comes 
 
34 
 
 from proteid, g,nd there are many other instances where the living 
 organism certainljr produces fat from proteid. 
 
 (2) In favor of the theory that the fat is a deposit from the 
 blood are the results of many experiments showing that the fat m 
 the livers of dogs poisoned by phosphorus may be varied according 
 to the character of the depot-fat. (Lebedefi— linseed oil; Eosenf eld- 
 mutton fat.) 
 
 Fischler perfused isolated kidneys with soap and found fatty- 
 deposits in the tubule cells. In infarcts fatty degeneration occurs in 
 the periphery near blood vessels, indicating that here only the living- 
 cells are capable of absorbing fat from the blood. 
 
 These and other similar experiments indicate that at least some- 
 of the fat in fatty degeneration of viscera is directly absorbed from 
 the blood by the injured cells. 
 
 (3) That some of the fat in .fatty organs arises vj^ithin the 
 cell is proven by the facts that many organs showing fatty degenera- 
 tion yield only a normal amount of fat by chemical extraction, and 
 that organs undergoing aseptic autolysis outside of the body may- 
 show typical appearances of fatty degeneration and more extract- 
 able fat. The fat appearing under these conditions must have existed 
 either in proteid, or in the form of some more complex fat-like 
 principle such as lecethin, from which it is split off during degenera- 
 tion, or in the form of an invisible emulsion from which it is thrown 
 down, possibly by the development of acids in the cell. 
 
 Hence it is probable that fat in cells arises at different times: 
 from all three of the sources mentioned, i. e., from cell proteid, from 
 the blood, and from invisible fat or fat-like principles in the cell. 
 
 Whatever may be the final outcome of the controversy it remains- 
 true that cells exhibit fatty globules under two distinct conditions: 
 
 (1) As a result of an acute or chronic degenerative process — ■ 
 fatty degeneration. 
 
 (2) As a result of a more or .less physiological process designed 
 for the storage of fat in the hoij— -fatty infiltration. 
 
 In fatty degeneration the globules are usually small and numer- 
 ous while the remaining protoplasm shows granular or hydropic 
 degeneration and loses its glycogen. In fatty infiltration the globules 
 are less numerous and larger. The two processes however are not 
 distinct but many transitions exist between them. 
 
35 
 
 In the pathogwiesis of fatty changes deficient oxydation is the 
 essential factor. A lack of oxygen in the system canses increased 
 destruction of proteids with tlie formation of fat and nitrogenous 
 cleayage products of proteid metabolism (urea, leucin, tyrosin, and 
 ammonia, etc.). The same lack of oxygen leads to deficient consump- 
 tion of the fat produced, which remains in the cell, interferes with its 
 function, and finally disturbs its structure. 
 
 The chief clinical conditions leading to fatty changes in the 
 cells are toxemia of bacterial or chemical nature {yellow fever, phos- 
 phorus poisoning) and anemia {pernicious anemia). Local fatty 
 changes are usually referable to local disturbance of the circulation 
 by partial occlusion of blood vessels. 
 
 Fat inrasion or lipomatosis are terms applied to the growth of 
 true fat cells between the elements of an organ, as in the heart muscle 
 or pancreas, whereby these elements become compressed and atrophied. 
 
 Mucous Degeneration. The transformation of cell substance 
 into mucus occurs physiologically in the goblet cells of mucous mem- 
 branes and in the connective tissue of the umbilical cord. Patho- 
 logically it likewise afliects epithelium and all members of the con- 
 nective tissue series. It arises in many forms of chronic disturbance 
 of nutrition, in tumors, but rarely in acute inflammation. As a 
 result of acute purulent inflammation there may be a deposit of 
 mucin in the tissues from the nuclei of leucocytes, which is very slowly 
 absorbed and may cause permanent damage to the tissue. 
 
 Physically, miieiis has a chai-acteristic slimy character, swelling 
 in water, and appearing in cells or tissues as a homogeneous or stringy 
 basophile mass. As it does not pass through membranes it is not 
 readily absorbed from tissues. Chemically, mucus varies in different 
 situations, but is always a combination of albumen and a colloidal carbo- 
 hydrate, the latter yielding a sugar when heated witli a strong acid. 
 Mucus is soluble in alkalis, and precipitated by acetic acid or alcohol. 
 The pseudo-mucin of ovarian cysts, however, is not precipitated by acetic 
 acid, and does not yield a reducing substance when heated Avith acids. 
 
 The exact. mode of origin of mucin from the cells is not under- 
 stood, but nuclear elements are chiefly concerned in its production. 
 In some cases the material is more homogeneous, denser, and more 
 acidophile than ordinary mucus, and has the characteristics of the 
 colloid substance of the thyreoid gland. Its formation is called 
 colloid degeneration. Colloid is not precipitated by acetic acid or 
 alcohol but swells in these agents. It forms solid homogeneous or 
 concentrically striated masses, usually in the thyreoid or other glands, 
 or about cerebral vessels where it may become calcified. 
 
36 
 
 On account of the variable chemical composition of many de- 
 generative products showing the physical characters of mucus, the 
 present tendency is to avoid the use of the terms mucoid and colloid 
 degeneration and to employ for both the term "gelatinous," which 
 is non-committal regarding the chemical nature of the material. 
 
 The Hyaline Degenerations. The appearance of firm homo- 
 geneous material in tissues is called hyaline degeneration. Two dis- 
 tinct varieties of this change are of widespread occurrence, viz., 
 (1) simple hyaline, and (2) amyloid, lardaceous, or waxy degenera- 
 tion. 
 
 iSimple hyaline material resembles amyloid in its resistance to 
 acids and alkalis, and in its acidophile staining tendency, but amyloid 
 is distinguished by yielding a mahogany brown color when treated 
 with sulphuric acid and tincture of iodine. 
 
 Hyaline maierial ^'aries in composition, sim-e almost any cell or 
 tissue may become hyaline. Its principle forms are the hyaline trans- 
 formation of connective tissue, the changes produced in cells by coag- 
 ulation necrosis, the fusion of tissue elements with fibrinous exudate, 
 agglutinated thrombi of red blood cells, the homogeneous changes in 
 the intima of blood vessels, hyaline renal casts, and the homogeniza- 
 tion of muscle fibres of Zenker s degeneration in typhoid fever. A 
 regressive change in the cell protoplasm due to disturbed nutrition 
 is the chief factor in its pathogenesis. 
 
 Amyloid is a glassy, firm, translucent material, which gives the 
 mahogany brown color with iodine and stains red with methyl violet. 
 It resists decomposition, digests slowly with pepsin if comminuted, 
 and breaks up leaving nuclein and yielding leucin and tvrosin. 
 
 Organs containing much amvloid are enlarged, firm, elastic, 
 and shiny, and the waxy masses are often visible to the naked eye. 
 {Sago-spleen.) 
 
 Mio-oscopically. amyloid is always a deposit of material between 
 the cells which causes atrophy of the cells or their fusion with the 
 amyloid substance. The deposit regularly begins beneath the endo- 
 thelial cells of small blood vessels, often reaches a considerable volume 
 and even produces tumor-like masses, as in the trachea. The liver 
 may be almost completely replaced by amyloid. It involves the reticu- 
 lum and vessels but not the cells of viscera. In each organ the deposit 
 takes characteristic forms, as the sago-spleen, the waxy glomeruli of 
 the kidney, etc. 
 
37 
 
 Amyloid occurs chiefly in chronic tuberculosis, syphilis, and 
 chronic suppuration. It has been produced experimentally hj incit- 
 ing prolonged suppuration with various bacteria or with injections 
 of turpentine. In these experiments the blood contains considerable 
 quantities of a substance resembling glycogen. In the pathogenesis 
 of amyloid deposits two main factors are probably concerned: 
 (1) The general disturbance of the blood occurring in chronic sup- 
 puration and marked by the appearance of glycogen in the plasma 
 and leucocytes, and (2) a local disturbance of the tissue cells which is 
 responsible for the deposit of the glycogen-like material in the form 
 of amyloid. 
 
 There seem to be many intermediate substances between glyco- 
 gen, am3doid, hyaline, and the mucins. 
 
 Glycogenic Degeneration. The appearance of glycogen in cells 
 which do not normally contain it or its accumulation in abnormal 
 quantity in cells which normally contain glycogen, is called glyco- 
 genic degeneration. 
 
 Glycogen appears in the form of homogeneous shiny granules 
 within or between the cells. The granules yield a brownish color with 
 iodiue, which disappears on the addition of saliva, or during heating. 
 Being very soluble in water glycogen is best demonstrated by treating 
 the cells with iodine dissolved in mucilage of acacia. 
 
 The liver cells normally contain a variable quantity of glycogen. 
 In diabetes the glycogen of the liver is much increased and it appears 
 in many other tissues, as the kidney, brain, and blood. During 
 active suppuration glycogen, probably derived from disintegrated 
 tissues, is demonstrable in the leucocytes and blood plasma, from 
 which it may be deposited in the tissues as amyloid. Glycogen is 
 often abundant in tumors, especially in those of embryonal type or 
 origin. 
 
 Necrosis. 
 
 Tissue cells, when deprived of nutriment, or brought into imme- 
 diate contact with violent poisons, or long exposed to their action, 
 undergo serious disturbance of their metabolism, extensive morpho- 
 logical changes, and rapidly die, by processes called necrosis. 
 
 I^ecrosis means much more than simple death of cells, and in- 
 volves especially characteristic changes in cell structure which result 
 from disturbance of the cell ferments and chemical changes in its 
 proteids which precede the cessation of all vital activity. Death of 
 
38 
 
 the cell often results from a slower process which passes through 
 various stages of degeneration, in which case the term necroUosis- 
 ma)' be employed. 
 
 Etiological Classified lion. (1) Necrosis from circ^ilatory disturb- 
 ance takes the form of ischemia from throml.(..sis and eml.ohsm, or 
 stasis, as in inflammation. 
 
 (2) Necrosis from direct injury of tissue. The injury may be 
 .mechanical, thermal, or bacterial. 
 
 (3) Necrosis from nervous influences. The nervous disturb- 
 ance may result from loss of trophic or vaso-motor control as m 
 syringo-myelia, or from ergot poisoning. 
 
 Anatomical Clasfiipmlion. Tlie forms of necrosis are ■usually 
 classified according to their gross and microscopical appearance, as 
 follows : 
 
 (1) Coagulation necrosis. 
 
 (3) Liquefaction necrosis. 
 
 (3) Casseous necrosis. 
 
 Although typical examples of these varieties are easily recognized, 
 they do not represent entirely distinct processes, but rather different 
 phases of one process which may be encountered at different stages 
 or be variously commingled. 
 
 Necrotic cells present two main characteristics: (1) Loss of 
 stainable nucleus. (2) Increased affinity of tlie CYtopla,sin for acid 
 dyes (eosin). 
 
 (i) Coagulation Necrosis is most, often seen in infarcts 
 where it results from loss of blood supply, and it may occur in any 
 tissue which contains much coagulable proteid. In the gross the 
 dead tissue is firmer than the normal, light in color if anemic but 
 dark red or black if infiltrated with blood. 
 
 Microscopically the outlines of the cells are preserved, they 
 stain deep red with eosin, and their protoplasm is usually homo- 
 geneous and rather opaque. In the early stages the nuclei may be 
 partially demonstrable but they soon disappear by one of two pro- 
 cesses, karyolysis or karyorhexis. 
 
 Karyolysis signifies the gradual loss of staining reaction of the 
 nucleus without disturbance of its form. All trace of the nucleus 
 finally disappears. 
 
39 
 
 Karyorhexis is the splitting up of the chromatin into densely- 
 staining (pyknotic) granules or rings which later lose their staining 
 reaction and disappear. 
 
 The mode of origin of tlie clianges in coagulation necrosis is not 
 fully undei-stood. The homogeneous appearance of the cells and the 
 firm consistence of the tissue are due to a form of coagulation of the 
 cell proteids. In some cases an intercellular exudate also coagulates in 
 the form of fibrin masses and fibrils, and the cells may at times absorb 
 some of the exudate. In the nuclear changes the development of acids 
 by disturbed cell ferments may account for the destruction of the fatty 
 nuclear envelop (Albrecht) and the dissemination of chromatin drop- 
 lets, as in karyorhexis, while the fading of the nucleus must be accom- 
 panied by a loss of nucleic acid and diffusion of nuclear elements in 
 the cytoplasm. 
 
 In the central parts of anemic infarcts the dead cells usually 
 retain their form^ are devoid of nuclei, but the cytoplasm is finely 
 granular and only slightly eosinophile, instead of being homogeneous 
 and opaque. This process may be called simple necrosis. In rare 
 instances of coagulation necrosis the homogeneous cytoplasm is broken 
 up into coarse grannies. 
 
 (2) Liquefaction Necrosis. Necrosing tissues instead of be- 
 •coming firmer by coagulation may soften and liquefy. This process 
 ■occurs under three main conditions: 
 
 (1) In infarcts of the brain the comparative lack of coagulable 
 material and excess of fatty elements often leads to early fluidifica- 
 tion of the dead tissue. 
 
 ( 2 ) In abscess formation and some forms of diphtheritic in- 
 flammation the tissues and exudate are fiuidified by combined action 
 of bacterial and tissue ferments. 
 
 (3) In gangrene or gangrenous inflammation tissues resisting 
 ordinary fluidifying agents, are subjected to the action of strong pro- 
 teolytic ferments derived chiefly from the putrefactive bacteria and 
 together with the exudate are fluidified and decomposed. 
 
 In the liquified material are mingled leucomaines, albumoses, 
 amido-acids, diamins, and other proteid and fat decomposition 
 products, besides bacterial derivatives, so that any absorption such 
 as may occur when the neighboring circulation is active is followed 
 by severe constitutional disturbance. 
 
 (3) Caseous Necrosis. Xecrotic tissues may become gradually 
 transformed into more or less dessicated cheesy material, or the 
 
40 
 
 necrosis may from the first follow this type. Microscopically such 
 necrotic masses are composed of acidophile granules of cell detritus 
 and fibrin, the outlines of the cells are completely lost and nuclear 
 fragments are usually unrecognizable. A considerable proportion 
 of fatty principles may be present, and eventually calcification may 
 occur. Caseous necrosis is most frequent in tuberculosis and syphilis 
 and in these lesions various transitions from simple or coagulation 
 necrosis may be observed. 
 
 Miscellaneous Forms of Necrosis. The course taken by ne- 
 crotic processes depends much upon the structure of the affected 
 tissue. Fat necrosis of a peculiar type occurs in the pancreas and 
 abdominal fat, from the action of extravasated pancreatic juice con- 
 taining steapsin and often mixed with biliary principles. These 
 agents cause saponification of the fat and liquefaction necrosis of 
 the surrounding connective tissue and epithelium. The necrotic areas 
 of fat may appear like miliary tubercles throughout the omentum 
 and pancreas, or these may be obscured by a hemorrhagic exudate 
 and diffuse areas of fat necrosis. 
 
 Microscopically, the fat cells show many acicular crystals of 
 fatty acids, or the periphery of the cell may become granular and 
 acidophile. Later, with complete saponification, the cell becomes 
 opaque and stains with hematoxylon, the outlines of the cells dis- 
 appear, and finally with the addition of necrotic exudate the tissue 
 may be converted into a semifluid caseous mass. 
 
 Necrosis of bone results in the death of considerable areas of the 
 compact tissue of the shafts of long bones which may become dense 
 and ebonized. Such a mass of dead bone may be thrown off by a 
 reactive inflammation as a single sequestrum. Tuberculosis of bone 
 usually produces certain inflammatory changes before necrosis is 
 reached which result in the dead bone being discharged in the form 
 of fine spicules, in the process known as caries. Necrosing cancellous 
 bone is also usiiallv broken up into spicules. 
 
 Regeneration of Cells. 
 
 A very important part of the reaction to external irritants con- 
 sists in regenerative processes in the affected cells. The remarkable 
 regenerative capacities displayed by the cells of low animals are 
 approached only by the epithelial cells in man, and yet even in the 
 highest mammals every specific cell except the adult ganglion cell 
 is capable of some degree of multiplication. 
 
41 
 
 As a rule, the higher the animal and the more specialized the 
 tissue the greater is the degree of degeneration and the less the power 
 or regeneration exhibited after injury. {Regeneration in the eartli- 
 worm. Prognosis after cerelral wounds.) 
 
 The ultimate cause of the multiplication of cells may be referred 
 to two factors : 
 
 (1) The renlo^■al of tissue tension which limits the growth 
 of cells in the organism, and (2) the formative stimulus of exter- 
 nal irritation. The two factors are often combined. 
 
 Wlien the nerve fibres of the spinal cord degenerate and atrophy 
 the glia cells experience some relief of tissue tension and proliferate 
 until the gap produced by the loss of nerve fibres is filled. Such 
 a regeneration seldom if ever exceeds immediate requirements. On 
 the other hand when a continuous discharge flows over the nasal 
 mucosa the irritated cells proliferate extensively and produce poly- 
 poid outgrowths wliich are a detriment to the organism. 
 
 \\'e may thus distinguish a strictly reparative and a liy per plastic 
 regeneration. In chronic processes such h)'perplastic regeneration 
 although it may not be bedeficial, is always under the control of 
 the organization, but it is probable that inflammatory hyper- 
 plastic regeneration may gradually or suddenly lose the controlling 
 influence of tl'o organization and l)ecome a neoplasm. In a group 
 of lesions inflammatory h3']ier]flasia of cells reaches a degree equal 
 to that of many true neoplasms, yet the clinical features indicate 
 that the processes are not truly neoplastic, since they subside when 
 the irritant is removed. The adenomatoid liyperplasia of the uterine 
 mucosa and of the prostrate gland in chronic inflammation are ex- 
 amples of such a process. In still other cases it is impossible to de- 
 termine whether or not the hyperplasia is inflammatory or neoplastic, 
 as in psuedo-leukeniia. These conditions indicate that regenerating 
 cells exhibit all degrees of freedom from the control of the organiza- 
 tion. 
 
 In regeneration cells multiply chiefly by mitosis, but to some 
 extent in certain tissue:. l)y amitosis. (Blood cells, liver cells.) The 
 mitotic process is not always normal, but irregular, multipolar, and 
 abortive mitoses occur resembling those in tumors. Amitotic division 
 probably does not yield a fully propagative series of cells. 
 
 The new tissue produced is always of the same type as the one 
 proliferating but it usually shows the embryonal cliaracters of this 
 
42 
 
 tissue and only gradually, if at all, reaches the adult t}'pe of the 
 parent tissue. 
 
 The new cells and tissue may vary considerably in form ana 
 function from their progenitors. Columnar epithelium may be re- 
 placed by flat cells, and new connective tissue may be myxomatous. 
 This metaplasia is usually not permanent. 
 
 After injury, as in normal growth and repair, certain portions 
 of a tissue are more active in regeneration than others. In mucous 
 membranes it is the cells at the ba^es of tlie glands, in the liver 
 the cells of the bile ducts, in lymph nodes the cells of the germinal 
 centres, which respond most actively to a formative stimulus. Losses 
 of specialized tissue are not always repaired by actual new formation 
 of cells, but sometime:-, as in the liver, by increase in size of pre- 
 existing cells whose increased bulk fills the gap. Such a process is 
 called iiwrphallaxis (Morgan). 
 
 The laws governing the regeneration of injured cells and the 
 processes followed vary in each tissue and organ. 
 
 Regeneration of Eprtlxi'llum. Considerable defects in stratified 
 epithelium of skin and mucous membranes may be fully repaired by 
 multiplication from the deeper layers, but destruction of ciliated cells, 
 unles! very slight, is replaced by flat cells which later become columnar. 
 In the uterus ciliated cells are constantly replaced after menstruation. 
 
 Local defects of glandular mucous membranes are repaired by 
 proliferation of the basal glandular epithelium. New glands may be 
 produced to some extent but they are seldom perfect. In the liver 
 and most other glands isolated cells or small groups of cells may 
 be replaced by division of neighboring epithelium. Definite wounds 
 of thesi' organs incite pr:]]iferation of the specialized epithelium, and 
 more actively of the duct cells, which to some extent replace the de- 
 fect, but the formation of liver cords by proliferating bile ducts is 
 seldom complete, while all such wounds give rise to the formation of 
 new connective tissue. 
 
 Connective tissue structures are all capable of regenerative and 
 hyperplastic growth. After slight injuries the new cells and tissue 
 may show little change in structure, but after large wounds or in 
 progressive inflammations the new tissue may take one of several 
 types, viz.: (1) Rnund cell fiKsur. (2) Granuhilion tissue, (,3) 
 EvihrijontiJ connectire tissue. (4) Cieniriciul iissue. The majoritv 
 of productive inflammations give rise to one or more of these types of 
 tissue, and in some cases the growth may be-in as round ci-ll or 
 
43 
 
 granulation tissiie or connective tissue, and terminate in cicatricial 
 tissue. 
 
 Round cell tissue is composed of a framework of old or new 
 connective tissue supporting many mononuclear cells which are lym- 
 phocytes, plasma cells, multiplying fibroblasts, and endothelial cells 
 (piil3-blasts). Bound cell tissue occurs in subacute productive in- 
 flammations, especially in tuberculosis and syphilis, and around the 
 edges of growing tumors. 
 
 Granulation tissue is composed of a framework of loose growing 
 connective tissue and an excess of proliferating blood vessels which 
 often project in tufts from the surface giving it a granular appear- 
 ance. It contains many cells of the same type as round cell tissue 
 and often recently emigrated polynuclear leucocytes, phagocytic cells, 
 and occasionally giant cells. N'o nerves have been demonstrated in 
 such tissue, and the lymph circulation is usually imperfect. Granri- 
 lation ti -sue is often of excessive bulk. {Proud flesh.) Granulation 
 tissue is chiefly seen in the healing of abscesses, ulcers, and other 
 necrotic inflammations, but may arise as a subaciite or chronic pro- 
 cess without preceding necrosis. 
 
 Connective tissue of inflammatory origin has the characters of 
 cellular embryonal tissue. The new flbroblasts are round pol3'blasts 
 or fusiform connecti'^'e tissue cells. Intercellular substance is de- 
 veloped as a secretion from tlie fibroblasts or from elongated fibrils 
 which arise within the cytoplasm of these cells. At first these fibrils 
 are delicate and the matrix of the tissue has a myxomatous appear- 
 ance, later the fibrils become sharper and elastic fibres appear. 
 
 Xew blood vessels are present in moderate number, and the new 
 tisue is often edematous or infiltrated with leucocytes from these 
 vessels. Emigrated leucocytes and dividing endothelial cells are often 
 indistinguishable from multiplying fibroblasts in growing connective 
 tissue, but there is no evidence that either of these cells are transformed 
 into fibroblasts or take more than a temporary and jiasslvc joart in the 
 development of the new tissue. ' 
 
 N^cw connective tissue is principally found in the productive in- 
 flammations of viscera, and in the healing of aseptic wounds. 
 
 Cicatrical tissue is a dense acellular, non-vascular, fibrous product 
 which represents the terminal and permanent condition reached by 
 other forms of productive inflammation. It also develops slowly to 
 replace atrophied tissues in the condition known as replacement 
 fibrosis. {Spinal sclerosis, cardia.c fibrosis, scars.) 
 
44 
 
 Other members of the connective tissue series may appear as the 
 result of irritation. In inflammations of bone and cartilage these 
 tissues may be produced from the cells of the periosteum and peri- 
 chondrium. Osteoid tissue is a product intermediate between carti- 
 lage and bone in which the matrix is hyaline, aciilophile, but very 
 slightly calcified, and the cells are multipolar. In myositis ossificans 
 imperfect bone tissue develops from the endomysium. 
 
 'New fat tissue develops in the atrophying pancreas and^ in neuro- 
 pathic myositis, between muscles fibres. True lymphaclciioid tissue may 
 appear in many regions in pseudo-leukaemia and in the infectious 
 granulomata. 
 
 Striated iiaisrh' cells regenerate after injury liy multiplication 
 of the nuclei of the sarcoplasm in the injured fibres. At first multi- 
 nucleated bud-like processes develop on the ends of these fibres and are 
 projected into the supporting tissue. The new sarcoplasm gradually 
 develops striation and may split into an increased number of fibres. 
 New fibres may sometimes develop from separated portions of 
 nucleated sarcoplasm when these are connected with the intact fibre 
 by sarcolemma. There is no evidence of the new formation of heart 
 muscle cells, while, the regeneration of smooth muscle cells after in- 
 juries is but slight. 
 
 N"ew t>lood vessels develop from pre-existing capillaries by pro- 
 liferation of the endothelium. These cells first become swollen and 
 granular and lateral buds are projected which unite with similar 
 processes from other capillaries. ^Multiplying nuclei advance with 
 tl^e^e protoplasmic cv.rrlp and canalization of the cords rcsidts from 
 the pressure of the blood current. As the vessel enlarges formative 
 cells from the invaded tissue apply themsehes to the support of the 
 endothelium. 
 
 Leucocytes increase rapidly in the active inflammations. The 
 polynuclear cells are developed by multiplication of the mononuclear 
 neutrophile myelocvtes in the bone marrow. The Lymphocytes are 
 supplied bv proliferation of the larger basophile cells of the Ivmphoid 
 tissues and bone marrow. Eosinophile cells are derived from the 
 mononuclear eosinophile myelocytes of the bone marrow. The pro- 
 genitors of all these cells are notably increased in the marrow and 
 lymphoid organs during leucocytoses. Some multiplication of leu- 
 cocyte? may occur in the circulating blood, and eosinophile cells 
 multiply in inflamed tissues and in some cases arise in them by trans- 
 formations of other cells. 
 
45 
 
 Giant cells of several types form during the regenerative 
 processes of tissue cells. Tliey result from: (1) The multiplication 
 of nuclei, hj- direct or indirect division, without division of the cell 
 body, or (2) by the fusion of two or more cells. 
 
 B}' the first method are produced the giant cells seen in 
 inflammation of bone and which are derivatives of multinucleated 
 osteoclasts; the giant cells resulting from the incomplete absorption 
 of proliferating fragments of striated muscle cells; those derived 
 from proliferating fat cells; and many of those in sarcomata. 
 
 By fusion of several cells are produced the foreign-body 
 giant cells which envelop insoluble foreign particles, and often cho- 
 lesterin crystals. In tuberculosis peculiar giant cells form by multi- 
 ' plication of nuclei without cell division, by fusion of fibroblasts, and 
 by fusion of endothelial cells of capillaries. They are actively phago- 
 cytic and usually contain tubercle bacilli. Similar cells, are seen in 
 other infectious granulomata, in granulation tissue, and in many 
 other chronic inflammations. 
 
 Ganglion cells in the human adult are entirely incapable of 
 miTltiplication. Glia cells jirolifcrate in chronic inflammation and 
 degeneration of the central nervous system prodjicing a peculiar 
 t^-pe of tissue resembling connective tissue and containing various 
 altered forms of glia cells and a matrix composed of their fibrils. The 
 end product of the process is acellular and resembles cicatricial tissue. 
 In its formation true fibroblasts participate to some extent. 
 
 Xerve fibres may be regenerated so as to comjoletely restore the 
 function after extensive injuries of peripheral nerves, but the ends 
 of the divided nerves must be brought within a certain proximity. 
 
 After severance of a nerve trunk the axis cylinders and medullary 
 sheathes of the distal portions break i;p into fatty droplets and are 
 absorbed by cells developed from the proliferating nuclei of the 
 neurilemma. The proximal portion degenerates up to the first or 
 second node of Eanvier. (Wallerian degeneration.) Prom the intact 
 proximal end the axis cylinders now become swollen, grow out into 
 the collapsed medullary sheath, splitting up into an increased number 
 of new axis-cylinders about which new myelin substance and neuri- 
 lemma are developed. In amputation stumps the gTOwth of new axis 
 cylinders may be excessive, producing club-like swellings known as 
 amputation neuromata. 
 
 From the foregoing revie^v it is obvious that there is an 
 extreme variety of changes in tissue cells resulting from regenerative 
 
46 
 
 efforts following irritation and injury. In many forms of severe 
 exudative inflammation these changes, although present from the 
 first, are obscured by the exudate or by necrosis and only become 
 apparent in the healing process. In other cases the regenerative 
 processes form the chief feature of the inflammatory reaction, con- 
 stituting the important class of productive inflammations. Under 
 still other conditions the regenerative efforts of cells seem only dis- 
 tantly or indirectly connected with the causes of inflammation. Thus 
 the increase or connective tissue in the breast at the menopause may 
 be regarded as a nou-iiiflaiiiinatoii/ fibrous hyperplasia. Yet whenever 
 regeneration occurs apart from normal growth its ultimate significance 
 for tlie organism appears to be the same, which is chiefly a form of 
 reaction to irritation or injury. 
 
 Hypertrophy. 
 
 Hypertrophy is an increase in the size of a tissue resulting 
 from increase in the size of its elements. Hypertrophy is usually 
 associated with increase in the number as well as the size of the 
 elements. 
 
 Hypertrophy may be congenital or acquired. Congenital hyper- 
 trophy leads to malformations seen in new born infants (ichthyosis) 
 and to general or partial giant growths, or excessive growth of bones 
 {Leontiasis ossea), developing later. 
 
 Acquired hypertrophy often results from over\\-ork {Biceps mus- 
 cle. Left ventricle) and from occasional physiological prc3esses. 
 {Pregniinl uterus. Breast.) 
 
 Sfany slow hypertrophies are partly or wholly of inflammatory 
 origin, as corns, venereal warts, elephantiasis from filaria, prostatic 
 hypertrophy. Congenital hypertrophy must be regarded as a dis- 
 turbance of normal growth for which there is often a nervous basis, 
 and sometimes also a traumatic factor. Acromegaly is a peculiar 
 form of ])y])i'rtrophy affecting chiefiy the bones of the face and ex- 
 tremities and probably traceable to disorder of the pituitary body, or 
 to other nervous affections arising in the course of various diseases. 
 
 Atrophy. 
 
 Atrophy is a diminuition in the size of an organ resulting from 
 a decrease in the size and often in the number of its elements. There 
 are many examples of physiological atrophy of organs and tissues. 
 
47 
 
 {TJii/iiius Breast. Uterus.), and in such cases the process being usually 
 free from anj- distinct degeneratiye change, is called simple atrophy. 
 
 In pathological conditions atrophy is accompanied by some de- 
 generation of the affected tissue. {Degenerative atrophy.) Patho- 
 logical atrophy may be classed as : 
 
 (1) Senile {Pigment atrophy of liver, and heart.) 
 
 (2) Atrophy from impaired nutrition. {Marasmic infants. 
 Artertosclcrotk hidney.) 
 
 (3) Pressure atrophy. {Nutmeg liver. Aneurism.) / 
 
 (4) Atrophy from disease. 
 
 (5) Xeuropathic atrophy. {Infantile paralysis.) 
 
 In atrophying tissues, the cells are reduced in size and number, 
 the parench)-ma cells suffering more than the stroma and their fluid 
 principles being first absorbed. The matrix of cartilage may become 
 fibrillated. Bone tissue softens from absnrption of calcium salts. At 
 the same time the trabccula of organs may increase in tliicknei^s, and 
 in several instances (muscles, pancreas) the atrophied elements are 
 replaced hy fat tissue {fatty atrophy). The nuclei of the cells are 
 often shrunken^ into resistant homogeneous detritus, and pigment or 
 vacuoles may appear in the cells. 
 
 Hyperplasia, Hypoplasia, Metaplasia. 
 
 Hyperplasia is an increase in the number of elements in a 
 tissue. The new elements show little or no variation from the normal 
 type and the increase in their size which constitutes hypertrophy is 
 lacking. Hyperplasia however is often associated with hypertrophy. 
 Hi-perplasia is of inftammatory origin in excessive regeneration of 
 injured cells, or neoplastic in the development of tumors. Some cases 
 of hyperplasia seem to be intermediate between the inflammatory and 
 the neoplastic grades. 
 
 Hypoplasia is the defective development of an organ or tissue. 
 It usually depends on some injury to the developing germ layers or 
 is hereditary. Agenesia is a total failure of development of an organ. 
 The hypoplasia may display itself in the embryo or only after birth, 
 and in either case these abnormalities often form the basis of definite 
 disease. Dwarfism is an example of universal hypoplasia usually 
 
48 
 
 hereditary- It also results from congenital syphilis. Microicphalus 
 exists in most congenital idiots. Cretinism is a peculiar form of 
 hypoplasia ref-erable to congenital or acquired loss of function of the 
 thyreoid gland. In constitutio lymphatica there is congenital narrow- 
 ing of the aorta, imperfect development of the genital organs, per- 
 sistence of the thymus, and general lymphoid hyperplasia. 
 
 There is a peculiar altruistric relation connecting hyperplasia 
 of some organs. In anencephalic monsters there is usually alasence or 
 atrophy of the adrenals. 
 
 Metaplasia. 
 
 Metaplasia is the transformation of one tissue into another 
 of closely related type. The term also refers to similar changes in 
 the cells of a tissue, which are often a,;sociatcd with hyperplasia of 
 these cells. 
 
 Fat tissue may develop from mucous tissue by the fatty infiltra- 
 tion of fibroblasts and atrophy of the intercellular substance, and from 
 lymphadenoid tissue Ijy atrophy of lymph cells and fat aljsorption by 
 the cells of the reticulum. Eevorsion of these processes also occurs. 
 Bony or osteoid tissue forms from connective tissue, by deposit of 
 calcium salts and characteristic transformations of the cells. 
 
 Metaplasia of epithelium leads to the transformation of columnar 
 into flat or hornifying epithelitim, as in erosions of the cervix uteri, 
 or of flat epithelium into cuboidal as in atelectatic lung tissue. A 
 great -variety of metaplastic processes, especially between the members 
 of the connective tissue series, occurs in tumors. They result chiefly 
 from disturbance of nutrition, or represent attempts at adaptation of 
 the cells to changed environment. 
 
 INFLUENCE OF THE NERVOUS 
 SYSTEM UPON INFLAMMATION 
 
 The particular course taken by an inflammatory process is con- 
 trolled to a considerable extent by the nervous system. Cerebral in- 
 fluences alone have undoubtedly induced inflammatory phenomena. 
 Blisters have been produced in hypnotized patients by the application 
 of a cold poker and the suggestion that the poker was red hot. It 
 must be admitted as a fact of scientific demonstration that the mental 
 condition has an influence upon inflammatory processes without 
 
49 
 
 much regard to their exciting causes. This influence is more pro- 
 nounced in some classes of individuals than in others. 
 
 It is an important fact that iniiammation in an area supplied 
 by one portion of a nerve may excite some inflammatory disturbance 
 in area supplied by other branches of the same nerve. {Redness of 
 the face with toath-ache. i^i/inpailietk- ophthalmia.) 
 
 Processes in one part of the body may also affect the course of 
 inflammation in another distant part of the body. Samuel has shown 
 that the usual inflammatory reaction from scalding a rabbit's ear, 
 completely fails, if, after scalding one ear, the other ear or even a 
 leg be iinmersed for several hours in water at 15° C. Loss of sensa- 
 tion in a part has long been known to favor severe inflammation. 
 After section of the ophthalmic branch of tlie fifth nerve severe 
 ulceration of the cornea frec[uently follows unless the cornea is care- 
 fully protected. Yet it has been shown that the same irritant pro- 
 duces more severe inflammation in an anaesthetic part than in one 
 with intact sensation. Particularly severe bed sores form in patients 
 with spinal or cerebral injuries. 
 
 The separate influence of different portions of the nervous 
 system has been partly determined. If the influence of the central 
 nervous system is cut off', as by section of the spinal cord, the stage 
 of exudative inflammation follows more rapidly than in a normally 
 innervated part. If the sympathetic nerve filaments passing to the 
 rabbit's ear be divided the vessels dilate, inflammatory changes when 
 excited follow rapidly and healing is likewise more prompt. If, 
 however, the spinal cord filaments be divided, the vessels contract 
 under the influence of the s>'mpathetic, inflammatory changes follow 
 trauma more slowly, exudation is le?s marked, but stasis is more apt 
 to occur in the vessels, and gangrene more frequently follows upon 
 injury. The peripheral network of nerve filaments, and ganglion 
 cells surrounding arterioles and capilaries appears to be purely 
 sensory and the effects on the inflammatory process following its 
 destruction have not been determined. 
 
 CLASSIFICATION OF INFLAMMA- 
 TIONS. — NOMENCLATURE. 
 
 Inflammations are classified according to the most marked feature 
 of the process, which varies with the structure and position of the 
 tissue affected and with the nature and intensity of the irritant. 
 
5° 
 (i) Degeneration. 
 
 The inflammatory process may not go beyond degeneration, fol- 
 lowed by restitution or regeneration of tissue cells, while vascular 
 changes are slight and exudation is wanting . 
 
 A'ery mild chemical irritants or traumatism applied to cutaneous 
 or mucous surfaces or affecting deejoer tissues may cause only a cer- 
 tain grade of degeneration of tissue cells which is repaired with very 
 slight vascular disturbance not demonstrable after fixation of the 
 tissues. 
 
 In the infectious diseases all the internal organs are exposed to 
 the toxemia and the cells suffer some grade of degeneration. The 
 term status infectiosus is applied to this condition of the viscera 
 which is common to all infectious diseases. Since it is the cells or 
 parenchyma of the viscus which especially suffer, the change in the 
 viscera is commonly called parencli ijmatous degeneration. In the gross 
 such viscera present the appearance of cloudy swelling. 
 
 The type of degenerative process produced in the viscera varies 
 ■with the organ affected and with the disease, often in a characteristic 
 manner. ;Vlcohol, phosphorus, and yellow fever, induce chiefly fatty 
 degeneration; typhoid fever, pneumonia, and most acute infectious 
 diseases cause chiefly granular degeneration. 
 
 The grade of degeneration varies with the intensity of the pro- 
 cess and with its duration. In the severer forms congestion of the 
 vessels and a little exudation are frequently added, especially in the 
 kidney. 
 
 Different infectioras diseases and toxemias show a tendency to affect 
 especially different tissues and organs. 
 
 {a) In some cases this specific action depends on the more or 
 less exclusive affinity which the poison shows for certain tissues. 
 Thus tetanus toxin affects chiefly the nervous system, and this tissue 
 in man, by means of its fatty principles, is the only one which actively 
 absorbs tetanus toxin in the test-tube. Diphtheria toxin also affects 
 the nervous system specifiealh'. In malaria the hemopoietic system 
 suffers chiefiy on account of the location of the parasites in the red 
 cells. 
 
 (6) Or an organ may be chiefly affected because of its circula- 
 tory relation to the chief point of entry of the poison. In typhoid 
 fever and other intestinal infections the liver is most seriously affected 
 of the organs. 
 
5.1 
 
 (c) The general course of the disturbed metabolism in disease, 
 ma}', for reasons which are very imperfectly understood, bring about 
 very intense lesions in certain tissues. No satisfactory explanation 
 has been furnished for the hyaline degeneration or necrosis ( Zenker's) 
 of the rectus abdominus muscle fibres in typhoid fever; of the stea- 
 tosis of the liver in yellow fever; or of the frequency of nephritis in 
 scarlet fever. 
 
 The function of an organ always suffers when its cells are de- 
 generated but not ahvays in a degree proportional to the degeneration. 
 Complete inhibition of the function of ganglion cells occurs when the 
 cells exhibit very little or no demonstrable alteration. In acute 
 yellow atrophy the urea forming function may apparently persist 
 when tlie bulk of the organ is completely necrotic and disintegrated. 
 These facts indicate that the functions of complex organs are not as 
 closely dependent on their anatomical integrity as has been supposed. 
 
 Eecovery of the cells from the milder forms of degeneration 
 usuall}' follows promptly iipon removal of the cause. Advanced grades 
 of granular and hydropic and especially of fatty degeneration are of 
 serious prognosis, not only because they occur in grave general 
 diseases but also because such advanced changes in the cells tend to 
 progress after removal of the cause. In severe grades of degenera- 
 tion isolated cells may become necrotic and many are exfoliated, 
 but all of these may be replaced by new cells of the same type. 
 
 (2) Exudative Inflammation. 
 
 Exudative inflammation is marked by vascular changes and exu- 
 dation of serum, fibrin, pus, and blood. The character of the exudate 
 varies greatly according to the intensity of the irritant and the 
 structure of the tissue. 
 
 If the exudate consists largely of serum the ■ process is called 
 seroiks inflammation, if of fibrin, fibrinous or croupous^ and if of pus, 
 purulent iii/famiimiioii. There are also various combinations of these 
 types. 
 
 When a tissue is thickly infiltrated with leucocytes, without 
 necrosis, the term phlegmonous inflammation is often used. These 
 orades of inflammation vary principally with the nature of the irri- 
 tant, but only vascular tissues are susceptible of markedly exudative 
 processes. The particular course and effects of the exudative process 
 depend upon the structure and location of the tissue. 
 
52 
 
 (a) In Connective Tissue all the cells suffer more or less 
 alteration, that of the carpillary endothelium facilitating the exudate. 
 The intercellular substance is swollen, the fibres separated, and all 
 the elements are infiltrated by the serum or cellular exudate and the 
 tissue is red and swollen. The excess of blood raises the temperature 
 ■of the part, and compression or stretching of nerves causes pain. 
 
 \\'lien the process subsides, serum is readily absorbed by blood 
 and lymph vessels ; fibrin is more slowly fluidified and absorbed ; many 
 pus cells wander back into the blood and lymph vessels but more are 
 .autolyzed and their fluid products are absorbed. After an excessive 
 •exudation of pus and much degeneration of cells, a more or less per- 
 manent deposit of mucin from the nuclei of the leucocytes is apt to 
 l>e left in the tissue. After simple exudative inflammation without 
 necrosis, the regeneration of cells is of moderate grade and soon 
 iceascs, but after chronic processes the regeneration may be excessive, 
 producing more or less permanent thickenings. 
 
 When an inflammatory process of any type affects the supporting 
 ■connective tissue of a viscus it is called an interstitial inflammation. 
 .(Interstitial purulent nephritis.) 
 
 (b) Mucous Membranes. Simple exudative inflammations 
 •^re often limited to mucous membranes and are then called catarrhal. 
 The term catarrhal emphasizes especially (1) an exudate thrown off 
 from a surface, and (2) exfoliaticn of lining cells. 
 
 The changes affect (1) the stroma, which is composed of reticular 
 connectiA-e tissue, in the meshes of which lie many lymphocytes. The 
 stroma supports blood ve.;-se]s and a rich system of lymph vessels. 
 Important changes affect (2) the glandular layer which contains 
 jglands lined by epithelium. 
 
 The stroma suffers the usual changes of exudative inflammation 
 in connective tissue. The lymphocytes are often multiplied. The 
 ■exudate infiltrates the stroma and in favorable cases it reaches the 
 ■surface and is thrown off as a discharge mixed with mucus from the 
 glands. In some cases there is less discharge and more marked infil- 
 tration of the stroma. The exudate may be largely serous (coryza). 
 
 The glandular layer suffers from the exfoliation of linino- cells 
 often leading to superficial erosions or ulcers which are later fully 
 repaired by new growth of epithelial cells. The function of the glands 
 is disturbed. At first the secretion of mucus is inhibited (dry stage) 
 later it is increased, altered in quality and mixed with pus, and at the 
 same time the congestion of the vessels is to some extent relieved. The 
 
53 
 
 duration of the dry stage in catarrhal inflammations varies in different 
 mucous membranes and seems to bear some relation to the amount of 
 lymphoid tissue in the membrane. Abundant fibrinous exudates 
 sometimes form on mucous surfaces and adhere to them as a sort of 
 pseudo-membrane but without the necrosis of cells which occurs in 
 diphtheritic processes. {Chronic fibrinous hroncUtis.) This process 
 is called croupous or pseudo-membranous inflammation. 
 
 (c) Serous Membranes. In serous membranes the suberous 
 connective tissue suffers as usual, but the exudate, fl'hether serum, 
 filjrin, or pus, is usually poured out in large and often in enormous 
 quantities. Thus, a litre of highly albuminous serous fluid is often 
 thrown off by the pleura in a few hours ; a layer of fibrin one centimetre 
 thick may form in a few days; while empyema (purulent inflammation 
 of the pleura) frequently causes such a large exudation of serum and 
 pus that the lung is tightly compressed against the spine. A less 
 marked excess of exudate occurs in inflammations of joint cavities 
 and meninges. In all of these conditions the endothelial cells seem 
 to exert a secretory function. 
 
 In some exudative inflammations of serous membranes the ex- 
 udate is almost wholly thro«-n off the surface and there is little infil- 
 tration of the subserous tissue. This occurs in most cases of empyema 
 in infants, which may be cured Ijy aspiration, and in the purulent 
 catarrhal synovitis of Volkmann. In other cases the suberous tissue 
 is infiltrated and its layers split up by many leucocytes, as in empyema 
 in adults, which is seldom cured by aspiration. 
 
 (d) Lymphoid Tissue. In the lymph nodes and spleen the 
 supporting connective tissue suffers as usual in exudative inflammation 
 and there is commonly a jjronounced multiplication of lymphocytes 
 especially about the follicles. In the centres of the follicles the 
 endothelial cells are often multiplied and the lymphocytes displaced. 
 
 The framework of a lymphoid organ is a labyrinthine meshwork 
 of which the strands of reticular tissue are lined by endothelial cells. 
 One of the prominent effects of exudative inflammation may be the 
 exfoliation of many lining endothelial cells, often - without much 
 exudation, and this process is therefore rightly termed "catarrhal 
 inflammation," calling attention to the exfoliation of lining cells. 
 
 (e) Viscera. In the viscera the stroma may become swollen, 
 edematous, and infiltrated with leucocytes, and these exuded elements 
 may be found between the parenchyma cells and in the lumina of the 
 alveoli. Owing to the abundance of delicate capillaries in many 
 
54- 
 
 yiscera, otherwise mild inflammations are often attended with ex- 
 cessive diffuse or focal hemorrhages. The parenchyma cells are very 
 prone to suffer degeneration; their function is disturbed or inhibited; 
 and the secretions are often rendered pathological. 
 
 The ducts tend to show catarrhal inflammation. When the stroma 
 is exclusively affected it is called interstitial inflammation; if the 
 parenchyma is chiefly involved, parenchymatous inflammation; and 
 when all parts of the viscus are involved the process is called diffime. 
 These terms indicate the location but not the grade of the inflamma- 
 tory reaction. 
 
 Constitutional symtoms are prominent signs of exudative in- 
 flammations of viscera, owing to the marked disturbance of meta- 
 bolism in the affected organs, their rich vascular and sympathetic 
 nervous ' connections, and the disturbance of the functions of other 
 organs which the loss of secretions entails. 
 
 (f) Nervous System. The central nervous system is com- 
 posed of a delicate supporting connective tissue, specific glia tissue con- 
 taining' glia cells with many fine processes, ganglion cells and their 
 processes, and medullated or non-medullated nerve fibres. When a 
 process of any nerve cell is cut the entire peripheral portion of the- 
 fibre must degenerate. 
 
 The blood vessels are relatively deficient or lacking in adventitial 
 coats, the anastomoses of the larger arteries are few, and the smaller 
 arterioles are often "terminal" vessels without lateral anastomoses. 
 The lymphatic supply is abundant and somewhat peculiar in its 
 relations to the arachnoid spaces, and to the vessels of nerve trunks. 
 Moreover nervous tissue is specially susceptible to some bacterial 
 toxins and apparently also to endogenous poisons. Chemicallj', ner- 
 vous tissue contains a large proportion of labile fatty elements. These 
 characters partly explain the peculiarities exhibited by inflammatory 
 reactions in nervous tissue. 
 
 The chief features of inflammatory reaction in nervous tissue are : 
 (1) The ready occurence, great intensity, and wide extent of de- 
 generative processes. (2) The comparative failure of exudative pro- 
 cesses. (3) The tendency toward thrombosis of vessels, hemorrhage 
 and necrosis of tissue. 
 
 Necrotic Inflammation. 
 
 When exudative inflammation is so severe as to lead to death 
 of considerable areas of tissue the process is called necrotic inflamma- 
 
55 
 
 Hon. The necrosis here affects all the structures in a certain area, 
 and not merely isolated cells as in simple exudative inflamma,tion. 
 From the prognostic standpoint this class of inflammations is very 
 important since the affected tissue is never restored to its normal 
 condition, but the dead areas are replaced by connective and cicatricial 
 tissue, leaving scars. 
 
 According to their extent and intensity necrotic inflammations 
 are classed as follows : 
 
 I Simple 
 
 \ (a) Ahtscess formation. 
 Necrotic Inflammation / (b) Ulceration. 
 
 j Diphtheritic 
 I Gangrenous 
 
 (a) Simple Necrotic Inflammation. Intense bacterial or 
 
 chemical irritants often lead to such severe exudative processes that 
 an area of tissue is rendered necrotic, fluidified, and infiltrated with 
 pus, forming a localized abscess. Simple necrotic inflammation is 
 usually caused by bacteria, chiefly the pyogenic cocci, but has been 
 produced experimentally by nearly all pathogenic bacteria and by 
 chemical agents. In connective tissue the circulation is completely 
 occluded by intravascular stasis and pressure from excessive exudate. 
 The bacterial or chemical irritant itself exerts an intense necrotic 
 action, and fluidification of the tissue and of the abundant purulent 
 exudate results from the action of proteolytic ferments supplied by 
 the tissue cells, the leucocytes, and the bacteria. 
 
 The abscess may present three zones : ( 1 ) A central fluid zone of 
 pus and cellular detritus. (2) A middle zone of marked leucocytic 
 infiltration and degenerating tissue cells. (3) A peripheral zone of 
 congestion and moderate exudation. 
 
 The outcome of an abscess may be: 
 
 (1) Evacuation of the pus, and' healing by granulation tissue, 
 cicatricial tissue, and a scar. 
 
 (2) Encystment of the pus with fibrous wall. 
 
 (3) Chronicitr. The walls of the abscess may be held apart, 
 infectinn and suppuration continue, and a chronic pyogenic membrane 
 persists until the death of the patient occurs from cachexia marked 
 by anemia and amyloid changes in the viscera. (Chronic empyema.) 
 
56 
 
 In mucous and serous membranes and in cutaneous surfaces the 
 same factors lead to the death of a superficial area of tissue which is 
 readily thrown off as a slough leaving an inflamed granulating exca- 
 vation called an ulcer. Such ulcers may be healed by the formation 
 of granulation tissue and the inward growth of lining epithelium. 
 Specialized glandular tissues are not reproduced after such lesions, 
 and a smoothly covered scar always persists. 
 
 In the viscera, abscesses, focal necroses, and death of larger 
 areas of stroma and parenchyma occur. In pyemia miliary abscesses 
 in many viscera are seen with little disturbance of the unaffected 
 parenchyma, but in most instajices visceral abscesses are of large size, 
 their walls are imperfectly demarcated, outlying areas of tissue be- 
 come necrotic from infarction, and the abundant circulation favors 
 general toxemia and metastasis. In favorable cases evacuation or 
 encystment may follow, granulation tissue replaces the destroyed 
 tissue, and after contraction of the cicatrix, considerable defects may 
 be obliterated by morphallaxis. Minute focal necroses may be restored 
 by parenchyma cells but larger lesions leave minute areas of fibrosis. 
 
 Diphtheritic Inflammation. Diphtheritic inflammation signifies 
 an exudative process in which there is rapid and diffuse necrosis of 
 superficial tissues. It affects chiefly the mucous membranes, some- 
 times the skin, and a similar process travels up mucous membranes 
 and involves the viscera. Bacillus diphtlieriae and streptococcus 
 pyogenes are its usual exciting agents, but other bacteria and some 
 chemical agents may be concerned in some cases. 
 
 In the mucous membranes, the necrosis may be very superficial, 
 involving only the lining epithelium and producing superficial erosions 
 which may be healed by proliferation of the surroiinding intact 
 epithelium. It usually involves large areas of the mucous surface. 
 
 As a rule the necrosis involves the whole glandular layer, or 
 passes through the submucosa, or even causes perforation of all the 
 coats. Such lesions are also widespread, and if recovery follows 
 healing proceeds by the growth of granulation tissue, and the forma- 
 tion of extensive scars covered by lining epithelium. 
 
 The exudate in diphtheritic inflammation is usually abundant 
 and often contains a large proportion of fibrin which coaonlates on 
 the surface entangling necrotic exuded blood cells, tissue cells, and 
 bacteria, and adhering tightly to the surface as an opaque yellow 
 false membrane. Hence diphtheritic inflammation is sometimes called 
 
57 
 
 pseudo-mernbranous, but pseudo-membranes also form from exuded 
 fibrin ^\-it]iout necrosis of tissue. In very severe cases however the 
 exudate may contain little fibrin, and the necrosed tissues may be 
 rapidly fluidified, mixed with blood and pus, and discharged without 
 the formation of a false membrane. In connective tissues diphtheri- 
 tic inflammation is not infrequently seen but is seldom fully recogniz- 
 able, being often classed with phlegmonous or gangrenous processes. 
 Here it is marked as usual by rapid diffuse necrosis and iiuidification. 
 of tissue or, when fibrin is abundantly exuded, by necrosis and coagu- 
 lation. {Diphtheritic erysipelas.) 
 
 In viscera diphtheritic inflammation may occur by extension: 
 along mucous surfaces leading to these viscera, as along the bronchi 
 to the lung, through the bile ducts into the liver, or up the ureters to- 
 the kidney. On reaching the viscus its local effects are very de- 
 structive, and visually fatal. 
 
 Gangrenous Inflammation. True gangrenous inflammation is 
 an exudative process in which bacterial ferments and occlusion of 
 vessels combine to destroy large masses of tissi^e in bulk, and in which 
 the dead tissue undergoes decomposition with the emanation of fetid 
 gases usually from secondary infection by putrefactive bacteria. In 
 certain predispo ed subjects (diabetics) ordinary pyogenic bacteria 
 may induce gangTcnous inflammation, and highly virulent strep- 
 tococci may Ijc the chief agents in some cases of infectious gangrene 
 {hospital fjitrif/iriic) , but tlio dt'i' .mposition of the dead tissue is 
 usually affected l)y anaerobic bacteria which produce gas. [Bac. aero- 
 genes ca])sulahts. Bar. oedeiiiatis maligni. Protrafi.) 
 
 Tbe lesion may affect any vaseidar tissue, producing large ulcers 
 of skin or mucous meml)ranes, extensive excavations in the viscera;, 
 and destroying all the tissues in considerable portions of limbs. The 
 exudate is usually scanty, contains dissolved blood, but few leucocytes 
 and little fibrin. Constitutional symptoms are severe and the process 
 is often fatal. In favorable cases the exudate becomes more purulent,, 
 a line of dcuarcation forms, the dead tissue is thrown off as a slough, 
 and recoverv follows w\i]\ extcnsi\'e deformity. 
 
 Infections gangrenous inflammation is often termed moist gan- 
 grene to distingiiisli it from senile or neuropathic gangrene, which is 
 of quite different origin and significance from gangrenous inflamma- 
 tion and is called rhi/ gangrene. 
 
58 
 
 Types of Ulcers. Three types of ulcers have been described: 
 
 (1) From loss of lining epithelium only. Sucli ulcers or 
 superficial erosions result from catarrhal inflammation, are usually 
 of small dimensions, and are completely healed by proliferation of 
 surrounding epithelium. 
 
 (3) From simple necrotic inflammation. These ulcers involve 
 varying depths of superficial tissues, are well circumscribed and lined 
 by granulation tissue. They heal with a scar. A particular variety 
 of simple necrotic ulcer is the round ulcer of the stomach in which 
 the gastric juice digests and excavates the dead tissue. 
 
 (3) From diphtheritic and gangrenous processes. Such ulcers 
 are of considerable depth, usually of large dimensions, and are lined 
 by necrotic tissue, or when healing, by granulation tissue. When 
 advancing irregularly and healing in places they are called serpiginous, 
 when rapidly destroying considerable tissue, phagedenic. 
 
 Ulcers may become chronic, when the irritant persists, or when 
 the circulation is imperfect. The usual basis of chronicity is found 
 in the growth of dense inflamed poorly nourished granulation tissue 
 from which there is a continuous purulent discharge. Such ulceis 
 are termed indolent. Many other descriptive terms are applied to 
 ulcers, based upon their principal characters which relate to their 
 niiniber and grouping, hose and secretion, and edges and vicinity. 
 
 Productive Inflammation. 
 
 Productive Inflammation is characterized by the development 
 of new tissue. In most examples of exudative inflammation there is 
 regeneration of lost cells, and in necrotic inflammation repair is 
 effected chiefly by the growth of new tissue, but in productive in- 
 flammation the growth of new cells and tissue is the prominent 
 feature from the first, the multiplication cells is progressive, the re- 
 generative efforts . are' not merely a reparative phenomenon but a 
 response to continuous irritation. 
 
 There may be no exudation whatever, in which case the process 
 is called simple productive inflammation, or exudation may be added 
 in productive iiifliimmation with exudation. The latter is much the 
 commoner form. 
 
 (a) Simple Acute Productive Inflammation. Cellular In- 
 flammation. Pure types of this process are rarely encountered 
 being furnished chiefly by the serous membranes. 
 
59 
 
 The new tissue is composed of new cells formed from fibroblasts 
 and endothelium, while the neighboring vessels are usually in a state 
 of congestion. In some cases plasma cell and smaller round cells 
 (polyblasts) may he present, and some of these may be emigrated 
 lymphocytes. Later the new tissue may approach the type of adult 
 fibrous tissue causing a permanent alteration in the structure of the 
 affected part. Owing to the cellular character of the new tissue 
 produced and the absence of marked vascular changes this process is 
 sometimes called cellular inflammation. 
 
 The development of a cellular inflammation requires a tissue 
 composed of cells with active proliferating capacities and an irritant 
 of moderate intensity and slow action. The purest examples have 
 been furnished experimentally from the application of mild caustics 
 to the peritoneum, and from the inoculation of the corneal epithelium 
 with vaccine. It is frequently seen on serous surfaces bounding areas 
 of more intense exudative inflammation, as on the pleura in pneu- 
 monia, or on the peritoneal surface near typhoid ulcers. There is a 
 form of menigitis in which the chief lesion is a multiplication of the 
 endothelial cells of the pia and arachnoid. Some of the lesions of 
 tuberculosis consist exclusively in the multiplication of endothelial 
 cells. 
 
 (b) Productive Inflammation with Exudation. Acute pro- 
 ductive inflammation is usually accompanied by vascular changes and 
 by exudation. The exudate consists of serum, fibrin, and mononuclear 
 leucocytes which outnumber the polynuclear. The new tissue is de- 
 rived from fibroblasts and endothelium, which are at first numerous 
 and are soon surrounded hy delicate intercellular substance and infil- 
 trated with seriim. It may contain many round cells (polyblasts) and 
 may also be infiltrated slightly by polynuclear leucocytes. New capil- 
 laries are developed from the affected vessels, but the new tissue is 
 often imperfectly vascularized and prone to various forms of degenera- 
 tion or e\-en necrosis. 
 
 In general the new tissue takes the type of round cell tissue or 
 crranulation tissue or connective tissue, all of which eventually become 
 fibrous. During recovery, the exudate subsides and may be removed 
 in the usual way, but the new tissue tends to progress and when 
 growth finally ceases leaves a permanent alteration of the affected 
 
 part. 
 
 It is eliaracteristic of productive infiammations with exudation 
 
6o 
 
 that they are subacute rather than acute in course, that their duration 
 is considerable, and that the acute stages are apt to be followed by 
 chronic productive inflammation without exudate. (Subacute 
 nephritis. ) 
 
 In the etiology of subacute productive inflammation microorgan- 
 isms are usually concerned, as in tuberculosis, syphilis, and other in- 
 fectious granulomata. These microorganisms do not secrete soluble 
 toxins but act to a considerable extent as mechanical irritants. Btido- 
 genous poisons are also probably responsible for such processes m 
 the viscera. 
 
 ' The effects of this type of inflammation vary with the structure 
 of the tissue in which it is located. 
 
 In connrdive tissue the exudate infiltrates both the old and the 
 new structures. The new growth adds to the thickness of the old, sur- 
 rounds and compresses blood vessels, and deforms their walls, and 
 forms irregularities on surfaces or adhesions between apposed sur- 
 faces. {Chronic peritonitis.) 
 
 In mucous membranes the exudate infiltrates the stroma, is 
 discharged from the surface, and a catarrhal inflammation is usually 
 established. The exudate is apt to be interstitial and to contain serum 
 and mononuclear leucocytes but few polynuclear leucocyte;, which 
 thicken the stroma and interfere with its nutrition and functions. The 
 new growtli of round cells and connecti\(' tissue also thickens the 
 stroma, obstructs blood and lymph vesjels, distorts and constricts 
 glands, and e\('ntually causes atrophy of lymphoid follicles. The 
 function of the glands is disturbed and they may be greatly increased 
 in size and number. (Adeiionuitoid, endometritis.) A mixed exu- 
 dative and ]3roductive inflammation may be limited to the stroma of 
 a mucous membrane while the exudate from the surface mav be largely 
 serous. (Subacute productive colitis.) 
 
 In the viscera the stroma is the seat of a diffuse new growth of 
 connective and round cell tissue replacing the parenchyma, while the 
 blood vessels are thickened and compressed, and the alveoli and ducts 
 are obstructed. The exudate infiltrates the thickened stroma and the 
 parenchyma and mingles with the secretion of the viscus. The 
 parenchyma suffers a variable grade, usually marked, of degeneration 
 and atrophy, and its function is seriously and to some extent perma- 
 nently impaired. (Suhacuie diffuse nephritis with exudation. Bron- 
 cho-pneiimouia.) In organizing pneumonia the fibrinoid exudate is 
 itself replaced by connective tissue and considerable areas of the lung 
 are finally converted into scar tissue. 
 
6i 
 
 Chrpnic Productive Inflammation. In chronic productive in- 
 flammation the new tissue is regularly of the type Of fibrous 
 tissue. It may first be comparatively cellular, containing fibroblasts 
 and lymphocytes (pol5'blasts), or if of slower formation it may have 
 the characters of adult connective tissue, or may finally become 
 densely fibrous. 
 
 Under some conditions the blood vessels may be niimerous, and 
 the tissue resembles granulation tissue. More often it is imperfectly 
 vascularized and tends to degenerate, soften, or become calcified. 
 {Endarteritis.) 
 
 Chronic productive inflammation may be (1) chronic and con- 
 tinuous from the first but (8) it usually follows an initial subacute 
 prodvietive process, and (3) frequently progresses with marked sub- 
 acute exacerbations interrupted by periods of partial quiescence. 
 During the exacerbations there may be exudation from the blood 
 vessels. {Bronchitis and emphysema. Chronic nephritis.) 
 
 This type of inflammation is produced by chronic irritation 
 affecting the stroma of viscera and mucous membranes. The irritant 
 may be an exogenous poison, as in plumbism, and alcoholism, or a 
 microorganism, ilany of the lesions of tertiary syphilis belong in 
 this cla.-s of inflammations. Finally it appears to result from a 
 previous degeneration of parenchyma cells of organs, when it is often 
 called replai-einent fibrosis, {('ardiiic fibrosis.) 
 
 In connective /i'.si?»e tliiokenings and adhesions are produced and 
 these may inclose collections of serum, especially when the process 
 affects serous membranes. {Chronic pleurisy and peritonitis. ) In the 
 intima of blood vessels it produces new tissvie which obstructs the 
 lumen, deforms the wall, and leads to softening and calcification. 
 {Arterio-scl erosis.) 
 
 In mucous membrnnes the connective tisue of the stroraa is in- 
 creased, and there may be hyperplasia or atrophy of lymphoid cells. 
 Polypoid outgrowths often appear, sometimes reaching a considerable 
 size. {Chronic rhinitis, endometritis.) The glands may be hyper- 
 trophic, or cvstic from constriction of their ducts, or may atrophy 
 from pressure of fibrous tissue. In some situations the number and 
 size of the glands may be so much increased as resemble a true 
 glandular neoplasm. {Adenomatoid endometritis.) The secretion 
 of the glands may be increased as in the hypertrophic condition in 
 chronic bronchitis, or diminished or aljsent, as in atrophic rhinitis 
 and gastritis. 
 
62 
 
 In the viscera there is a growth of connective tissue, sometimes 
 infiltrated- with round cells, beginning in the stroma and replacing 
 considerable areas of the parenchyma. The blood vessels are commonly 
 sclerosed and deformed, or obliterated, or replaced by amyloid. The 
 parenchyma cells are compressed and atrophic or exhibit many stages 
 and forms of chronic degeneration. Kegenerative efforts on the part 
 of the cells are sometimes a prominent feature. The functions of 
 the viscus are seriously and permanently impaired. 
 
 JMalignant tumors often develop on a basis of chronic productive 
 inflammation. (Chronic productive mastitis.) 
 
 Inflammation in Bone. 
 
 While the peculiar structure of bone lends many ■ peculiar char- 
 acters to inflammatory processes in this tissue yet these processes have 
 their homologues in the inflammatory reactions of other tissues and 
 are perhaps best comprehended when studied in comparison with 
 parallel changes in more vascular tissues. 
 
 Degeneration. Degenerative processes afEect both the cells 
 and the matrix of bone. 
 
 (a) Bone cells undergo granular and fatty degeneration, in 
 caries, osteomalacia, and in all forms of osteitis. The importance 
 of these changes is seen in the alterations in the bone matrix which 
 immediately follow the disturbance in the cells. 
 
 (&) Bone matrix undergoes two chief alterations, osteoporosis, 
 and osteosclerosis. Osteoporosis signifies a loss of calcium salts in 
 the matrix and thinning of the bony trabecula. The removg^l of the 
 salts is accomplished under the influence of the bone cells whose 
 nutrition is in some way disturbed, and also by means of special cells, 
 multinucleated osteoclasts, which are modified mesodermal cells. In 
 rachitis and osteomalacia, it is believed by many to result from the 
 action of acid products of disordered metabolism. After the loss of 
 salts the matrix may undergo further change and become fibrous and 
 atrophic or mucinous, or it may undergo fatty degeneration and 
 break down into structureless detritus. 
 
 Osteoporosis occurs in many forms of inflammation of bone and 
 constitutes the chief le:.ion in rachitis, osteomalacia, and in a specific 
 disease of bone known as rarefijing osteitis. 
 
 Osteosclerosis signifies an increase in the lime salts of bone 
 and a thickening of the bony trabecula, which often leads to oblitera- 
 tion of the lacunae and bone cells and the Haversian canals, so that 
 the bone becomes very dense and ebonized. The deposition of salts 
 
63 
 
 probably results from some change in the nutrition of the bone and 
 its cells. It may appear in necrosing bone. There is an hereditary, 
 and an acquired and usually senile form of osteosclerosis, in vhich 
 the bones are abnormally fragile. (Fragilitas ossium.) 
 
 Necrosis. ISTecrosis of bone occurs as a result of inflam- 
 mations of periosteum and marrow which in other tissues would not 
 lead to death of tissue. This is because, the nutrient arteries of bone 
 and the vessels supplied by the periosteum are enclosed in solid walls 
 within which an exudate rapidly obstructs the circulation. Bone 
 necrosis is therefore a form of anemic necrosis or infarction. 
 
 Depending upon the vessels occluded, the whole shaft, or only 
 the subperiositeal layers may necrose. In the dead bone all the cells 
 become necrotic and the matrix is either ebonized, or eroded by sur- 
 rounding fluids, especially by pus. The dead mass then acts as a 
 foreign body and along its edges is excited in the living tissues an 
 exudative inflammation, forming a line of demarcation. The necrosed 
 bone is then separated as a sequestrum by a process which includes 
 the following factors : 
 
 (1) The absorption of calcium salts from a thin layer of living 
 bone surrounding the sequestrum. 
 
 (2) The development, in this layer, of granulation tissue which 
 is capable of exudative changes. 
 
 (3) The development of a suppurative inflaramation in this 
 zone which causes further absorption and loosening of the sequestrum. 
 
 After removal of the sequestrum, large defects in bone may be 
 repaired through the formation of new bone by the periosteum. 
 
 Acute Exudative Inflammation of bone occurs as a part of 
 acute periosteitis or osteomyelitis. If it does not result in necrosis 
 the changes effect only the contents of the Plaversian canals. 
 
 Acute Suppurative Inflammation occurs in compact and can- 
 cellous bone producing a "bone abscess." The exudate of pus usually 
 begins in the marrow at the ends of long bones (tibia), causes ab- 
 sorption of bony trabecula, and the formation of a wall of granula- 
 tion tissue. The pus may infiltrate the surrounding Haversian canals. 
 Caries appears to be the homologue of subacute or chronic 
 necrotic inflammation of vascular tissues. It is usually of tubercu- 
 lous origin, but may complicate other forms of periosteitis. It is a 
 form of ulcerative osteitis which results in the death and discharge 
 of small areas of compact or cancellous bone. The exudative process 
 which accompanies it causes the absorption of lime salts from some 
 
64 
 
 portions of the bone while the remainder breaks up into small masses. 
 Moreover the calcium-free matrix also undergoes degeneration and 
 necrosis and is discharged as granules and fatty detritus. 
 
 As the ulceration progresses and becomes chronic there is a new 
 growth of granulation tissue and some efEorts at the formation of new 
 bone. 
 
 Productive Inflammation of bone occurs under several forms. 
 
 Rarefying Osteitis is essentiall}^ a productive inflammation of 
 bone in which there is a growth of new tissue resembling granulation 
 tissue, in Haversian canals, and an absorption of bony tissue. The 
 absorption results chiefly from the action of osteoclasts which are 
 found lying in niclies which they excavate in the bone, called How- 
 ship's lacunae. Absorption also occurs under the influence of the 
 disturbed bone cells, so that irregular channels formed by the ab- 
 sorption of bone and the coalescence of lacunae and canaliculi may 
 be found traversing the affected part. In cancellous bone portions 
 of trabecula may be completely isolated in this way and surrounded 
 h\ vascular tissue containing many round cells, capillaries, and 
 osteoclasts. 
 
 Formative Osteitis is a second type of productive inilammation 
 in bone. It occurs in the healing of fractures, in caries and necroses, 
 and in tuberculous, syphilitic, and other inflammations of bone and 
 periosteum. N'ew bone is laid down in a matrix of connective tissue 
 or cartilage under the influence of bone cells or periosteal osteoblasts. 
 These cells become surrounded by a fibrous or hyaline matrix, which 
 gradually becomes calcified. The intermediate stage of this process, 
 in which multipolar cells are surrounded by hyaline acidophile 
 matrix in which there is little or no calcium deposit, is called osteoid 
 tissue. Earefying and formative osteitis frequently coexist in dif- 
 ferent parts of the same lesion, so that the bone is absorbed at one 
 IDoint, thickened at another, and thereby greatly deformed. 
 
 In chronic periostitis, new masses of bone may cause local 
 thickenings of considerable extent, resembling tumors. {Inflamma- 
 iory exostoses.) 
 
 When inflammation of any type affects the bone marrow the 
 process is called osteomyelitis. In the marrow the changes pro- 
 duced are similar to those occurring in other lymphoid tissues, while 
 the effects produced on surrounding bony structures are similar to 
 those resulting from periostitis. 
 
 Finis. 
 
PRESS OF J. J. O'BRIEN & SON 
 
 122 EAST 23d STREET 
 
 NEW YORK 
 
Binder 
 Gaylord Bros. Inc. 
 
 Makers 
 Syracuse, N. V, 
 
 W. JAN 21, 1908 
 
 DATE DUE 
 
 Interlibra 
 
 ry Loaf. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 GAYLORD 
 
 
 
 PRINTED INU.*. A.