Chapter III: Part II: , Showing Predominance of Malarial Element . . . . 617 (2)

Even if tuberculous and scrofulous inflammations are regarded as inflammatory processes, modified by a specific cause and by peculiarities of the individual, the cancerous and sarcomatous inflammations are still to be considered as representing an association of inflammatory disturbances and specific new formations, the cause of the latter not being the cause of the former. As ordinary inflammations of the regions concerned may take place in the absence of the neoplasms, so may the {52} specific growth appear in the same regions without anatomical or clinical evidence of inflammation.

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

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

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

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

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

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

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

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

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

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

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

The distinction between acute and chronic inflammations is essentially one of convenience, and, when considered from the anatomical point of view, relates rather to the persistence of the results. These may be {54} present as a variously modified exudation or as a degenerated condition of the parenchyma of the organ or tissue affected.

Inflammation terminates in resolution, production, or destruction.

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

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

The productive termination of inflammation is manifested by the new formation of connective tissue. This tissue is variously designated, as the inflammatory process is limited to the surfaces of the body exposed to the air, or the surfaces of cavities and organs, or as it lies within organs or the deep-seated parts of the body. In numerous instances it becomes a permanent constituent of the body, and, as time is usually essential for its formation, its occurrence is indicative of a chronic, rather than an acute inflammation. Certain chronic inflammations are progressive in character, the production of connective tissue being continuous, with perhaps occasional intermissions, as in the chronic interstitial inflammations of organs and tissues. The new-formed tissue, which at the outset is rich in cells, becomes in time more fibrous, and associated with this change in structure is a physical modification, manifested by its shrinkage. This new formation may fill a gap resulting from the destruction of tissue in {55} the progress of an inflammation, when it is present as cicatricial tissue--the scar which is usually met with upon the surfaces of the body or of certain of its organs. When opposed surfaces are united by the new-formed tissue, the term adhesion is applied; the adhesions being present as fibrous bands, cords, or membranes. The pericardial milk-spots and thickenings, the tendinous or semi-cartilaginous, indurated patches of serous membranes and of the intima of arteries, are all regarded as manifestations of a chronic inflammation of these tissues. With the localization of the inflammation in the outer walls of the bronchi and blood-vessels a thickening of the external sheath results, called a peri-bronchitis, arteritis, or phlebitis, as the case may be.

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

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

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

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

Thrombosis and Embolism.

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

These terms were introduced by Virchow[17] to avoid the confusion which resulted from regarding the process and result as synonymous with inflammation of the vessel. All writers, even at present, do not adhere to this strictness of meaning. For a thrombus of the vulva indicates a clot of extravasated blood within the connective tissue of the labium; in like manner, a vaginal thrombus is the effused and clotted blood in the loose connective tissue surrounding the vagina. These exceptions are gradually disappearing, and the word hæmatoma, tumor composed of clotted blood, is being substituted in both instances. A cancerous thrombus represents a mass of cancerous tissue whose growth is extended along the course of a vessel, its wall having been penetrated. In general, however, the term thrombus, unless otherwise qualified, is used as first stated.

[Footnote 17: _Handbuch der Speciellen Pathologie und Therapie_, Erlangen, 1854, i. 159.]

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

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

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

[Footnote 18: Rollett, _Hermann's Handbuch der Physiologie_, Leipzig, 1880, iv. 1, 114.]

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

Although stagnation of the blood is often an important immediate cause of its coagulation, it is apparent, from the investigations of Durante[19] and others, that stagnant blood clots in the living vessels only when their endothelium is in an abnormal condition. With the co-existence of abnormal endothelium and stagnant blood, thrombi form with greater frequency and become more voluminous in a given interval of time.

[Footnote 19: _Wiener Medizinische Jahrbucher_, 1871, 321.]

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

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

Zahn[20] divides thrombi, according to their color, into red, white or colorless, and mixed varieties. The red owes its color to a large number of red blood-corpuscles, while the white and mixed forms contain various proportions of white blood-corpuscles and fibrin and a diminished number {58} of red corpuscles. The cause of this difference in the color of thrombi is to be sought for in their method of origin. When blood clots slowly in a dish, the heavier red corpuscles settle to the bottom, and the lighter white corpuscles form a superficial layer. Stagnant blood clotting rapidly furnishes a uniformly red mass. The red thrombus, like the red clot, is the result of the rapid coagulation of stagnant blood. The white thrombus, on the contrary, largely composed of white blood-corpuscles, represents a constantly increasing deposition of these from flowing blood. The mixed thrombi arise from a combination of both conditions, and are usually white at the outset. Thrombi formed in the heart and larger arteries are usually white, those in the auricular appendages and on venous valves are mixed, while red thrombi are more common in arteries and veins, since the conditions favoring their origin are more frequently met in such vessels.

[Footnote 20: _Virchow's Archiv_, 1875, lxxii. 85.]

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

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

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

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

Traumatic thrombi result from a direct injury to the vessel. This may be mechanical, as in the application of ligatures for the obliteration of vessels, the tearing of the veins during childbirth, and the infliction of wounds of every variety. The injury may likewise be chemical, from the action of caustics; somewhat analogous to which, are the effects of heat and cold. Allied to the traumatic thrombi are those which arise {59} from acute inflammation of the intima extending from wounds or inflammatory processes in the vicinity of blood-vessels.

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

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

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

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

Thrombi are also characterized by consistency and relative absence of moisture. A thrombus is brittle and dry as compared with a clot. In distinguishing between the two, difficulty arises only in the case of a thrombus which may have formed within a few hours before death. Post-mortem clots are moist, elastic, readily withdrawn from blood-vessels, and have a smooth and lustrous surface. Their color is either red, gray, grayish-yellow, or yellow, and is very often mixed. The lighter colors are due to causes which favor the precipitation of red blood-corpuscles before actual clotting takes place, or which occasion an increase of the white blood-corpuscles in fibrin. The thrombus becomes adherent to the vessel wall within a few hours, after its formation, in the case of the red thrombus, and at once, in the case of the white variety. A clot is never adherent, although it may seem so from its entanglement between the trabeculæ and {60} tendons of the heart and the cavernous framework of venous sinuses. Such apparent adhesions are easily recognized by the smooth, shining, intact intima which is disclosed after the removal of a clot.

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

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

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

[Footnote 21: _Die sogenannte Organisation der Thrombus_, Leipzig, 1877.]

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

The calcification of a thrombus takes place when the latter becomes impregnated with salts of calcium and magnesium. The condition may be present in thrombi which are exposed to a rapidly-flowing arterial stream, as well as in those which lie in venous pockets outside the course of the direct current of blood. The well-known phlebolites are examples of the latter variety. A calcified thrombus may be intimately united to the vascular wall, the results of calcification and organization being associated. Calcification and, in particular, organization represent favorable {61} events in the history of thrombosis, as through their occurrence the process comes to an end, and disturbances, either local or remote, are prevented.

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

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

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

Cohnheim lays special stress upon the presence of micrococci in the softened material, and it is generally agreed that the virulence of septic softening is connected with, if not due to, the presence of microbia. A septic softening may be induced by besmearing, with septic material, the outside of a blood-vessel containing a thrombus, and this form of softening is usually associated with those conditions favoring this relation. Such are the gangrenous wounds following surgical operations, the putrid inflammatory processes affecting the uterine wall after childbirth, the offensive inflammations of the middle ear, and the like. It is possible for a septic softening to occur independently of such contiguous or continuous relations with the surfaces of the body. It is considered, {62} however, that the micrococci present in a softened thrombus must have obtained admission from without through one of the surfaces of the body, mucous or cutaneous, or through undiscovered abrasions of even intact surfaces of peculiar structure, as the alveolar wall or the intestinal mucous membrane. The thrombus is regarded as affording a favorable soil for the growth and activity of the organism.

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

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

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

Vegetable parasites, like the bacterium and aspergillus, have also been included in the list, although the disturbances resulting from their presence are less due to mechanical obstruction than to colonization and growth. The experimenter uses the most various objects as emboli--bits {63} of wood, rubber, and glass, globules of mercury, fragments of tissue, etc. Emboli are to be regarded as of arterial or venous origin. The arterial emboli are carried toward the capillaries, while venous emboli are carried toward the heart. The effect of both is partly or wholly mechanical, and partly due to the specific properties of the constituents.

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

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

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

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

When an embolus is found, or embolism suspected, the source is always {64} to be searched for in those regions from which the affected part receives its blood. The source of arterial and portal emboli is usually found with ease, while the pulmonary embolus may come from so wide a region, the body-veins, that much time may be spent before its place of origin is discovered. An appreciation of the laws of the transfer of emboli renders such a discovery almost certain.

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

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

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

Litten,[22] on the contrary, who has furnished a recent contribution to this subject, claims that the hemorrhagic results of embolism are not accomplished through venous regurgitation, unless increased venous tension is produced by coughing, vomiting, and like efforts. His experiments lead him to maintain that arterial blood from surrounding tissues is supplied to the obstructed region through the anastomosing capillaries. The force is not sufficient to drive the blood through the capillaries into the veins beyond, but an accumulation takes place in the capillaries, which become dilated and distended. The escape of blood-corpuscles and {65} serum then takes place, the more freely, as Weigert[23] suggests, the larger and more numerous are the pre-existing spaces in the organ. Hence the infarction becomes the most characteristically developed in such organs as the lungs and spleen. Causes which obstruct the venous flow, as well as those which increase the arterial tension, promote the hemorrhagic infarction.

[Footnote 22: _Untersuchungen über den hemorrhagischen Infarct., etc._, Berlin, 1879.]

[Footnote 23: _Virchow's Archiv_, 1878, lxxii. 250.]

A necrosis of the part whose direct arterial supply is cut off takes place when the structure of the organ affected is such that the admission of arterial blood is wholly interfered with. This is the case in the heart and kidneys, and to a less extent in the spleen. The opportunity is presented for the diffusion of a fibrinogenous fluid, lymph or blood-serum, through the cells of the organ which contains the other essentials for coagulation, and the dead part presents the characteristics attributed by Weigert[24] to death from clotting of the protoplasm, coagulative or ischæmic necrosis.

[Footnote 24: _Ibid._, 1880, lxxix. 87.]

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

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

If the patient outlives these more mechanical results of embolism, the local changes taking place are those tending to remove the extravasated blood or the dead tissues. The embolus has become an obstructing thrombus, and its removal is accomplished in the manner already stated in connection with the subject of thrombosis. The wedge-shaped nodule of hemorrhagic infarction becomes decolorized through the absorption, in part, of the blood-pigment. That portion which is not absorbed remains at the site of the original lesion as granular or crystalline blood-pigment. A granulation-tissue is formed at the periphery, which extends into the infarcted region, very much as the endothelial and vascularized growth extends into a thrombus. Eventually, a patch of cicatricial tissue remains as the sole indication of the previous disturbance. This termination is rather suggested for the hemorrhagic infarctions of the lungs. The results are more apparent and more easily demonstrated in the case of the anæmic necroses, and the somewhat irregular depressions with wedge-shaped scars, seen upon the surface of the spleen or kidneys, call attention to the probable nature of the process giving rise to these results. A source of embolism must also be associated, that these scars may be regarded as of embolic origin. The embolic softenings of the brain are likewise represented in after years by losses of substance. The superficial, yellow patches or localized oedematous blebs, with corresponding atrophy of the convolutions beneath, call attention to a nutritive disturbance, as do cyst-like cavities in the deeper parts of the brain. Here, too, a source of embolism must be found, that {66} the local destruction of tissue may be attributed to embolic obstruction of vascular territories.

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

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

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

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

Effusions.

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

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

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

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

To appreciate the conditions under which pathological accumulations of fluid, whether effusions or exudations, may arise, it is desirable to bear in mind the essential conditions which prevail in the occurrence of transudation, since the former are likewise chiefly derived from the blood and are transuded through the walls of its vessels. These conditions are largely dependent upon the laws governing the diffusion of substances through an animal membrane, the vascular wall representing the filter. As a living membrane its relation is dependent upon vital as well as {68} physical conditions, and the former produce certain important modifications in the physical process of filtration.

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