turbances; but when large quantities enter the veins the right heart is found full of frothy blood and the pulmonary arterioles are occluded by small bubbles. Sudden death in these cases is not unusual. Some recent experiments in dogs seem to cast doubt on the seriousness of air-embolism, but the matter is not yet settled.

Fat-embolism.-Sudden death may occur when a large number of the pulmonary vessels are obstructed by embolic oil-drops. When the process is less extensive little disturbance arises, as the oil is soon broken up into droplets and passes through the pulmonary capillaries, or it may be absorbed in the lungs.

Pulmonary infarcts may be due to embolic occlusion of the blood-vessels, but also to obstruction of a bronchiole. Any kind of hemorrhagic extravasation in the lungs may assume a wedge-shape, because the area infiltrated is the wedge-shaped area included in the divisions of a terminal bronchiole. (For details, see the chapter on the Lungs.)

Metastasis. The process of metastasis of tumors and of infectious diseases is closely allied to that of ordinary embolism. Small particles of tumors in the one case, or of infected thrombi or tissue in the other, enter the blood-vessels or the lymphatic channels and are carried to neighboring or distant parts of the body, where they lodge in capillary-vessels. In the case of tumor-embolism the embolus may grow and occasion a metastatic nodule; in the case of infectious processes secondary foci of the infectious disease result.

THROMBOSIS.

Thrombosis is the coagulation of blood within the blood-vessels or heart during life. At the very beginning of the process the formation is not a coagulum in the ordinary sense, but subsequently coagulation is the essential feature. After death clots form within the heart and vessels, as in blood removed from the body. Causes. The conditions favorable to thrombosis are alterations in the blood-current, changes in the vessel-walls, and alterations in the blood itself. For the most part two or all of these conditions are present in cases of thrombosis.

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Alterations in the Blood-current.-Anything which slows the current, such as narrowing of the blood-vessels, weakness of the heart, or pressure upon the vessels, favors thrombosis. Complete arrest of the current in a part may lead to ordinary clotting, such as occurs post-mortem; but with careful precautions a vessel may be ligated at two points without the occurrence of clotting in the occluded portion-at least for a long time. Some change in the blood-vessel wall is generally necessary in addition. Thrombi due to slowing of the current are frequently seen in the heart, the vessels of the lower extremities, and in the sinuses of the brain in the course of exhausting fevers or other asthenic conditions. They are called marantic thrombi. In many of the latter micro-organisms have important etiologic relations.

Changes in the vessel-walls play an important part. Atheroma, inflammatory or degenerative changes in the vessels of areas of inflammation or necrosis, ligation and other traumatic injuries, and diseases of the endocardium are all examples of conditions leading

to thrombosis. In many cases of thrombosis apparently due to slowing of the current of blood, micro-organisms have been the more important factors, by causing primary infective lesions of the endothelium. Dilatation of the arteries (aneurysm) or veins (phlebectasia) or of the cavities of the heart acts largely by slowing the current of blood or by producing irregular currents.

Alterations in the Blood.-Experimentally, thrombosis may be induced by injection into the circulation of extracts of the thymus gland, the suprarenal bodies, the testicles, and other organs. These extracts contain large quantities of the fibrin-ferment regarded by Schmidt as an essential factor in coagulation. Pathologically, it is probable that the tendency to thrombosis in typhoid fever, sepsis, and other diseases is due to increase of similar fibrinforming factors in the blood. The name fermentation-thrombosis is applied in these cases. The importance of bacteria in the blood. has been sufficiently noted above.

According to Schmidt, coagulation is due to the reaction of fibrinogen (derived from the plasma) with fibrinoplastin under the influence of a fibrinferment (the two latter derived from the leukocytes). Fibrinoplastin is probably not essential (Hammarsten), while calcium salts are (Arthus and Pages).

Pathologic Anatomy.-The appearance and construction of thrombi depend upon the manner of formation.

When formed in consequence of almost complete stoppage of the circulation they are dark-colored, soft, red clots, similar in every way to post-mortem coagula; and under the microscope show fibrillar fibrin enclosing mainly red corpuscles.

Yellowish or white thrombi are formed slowly from actively circulating blood and are more consistent. Their composition will

be understood from the mode of formation. In the normal circulation the red corpuscles and blood-plaques move in a column in the center of the stream, separated from the wall of the vessel by a plasmatic zone in which the leukocytes may be seen. When the circulation is slowed the plaques approach the vessel-wall and tend to adhere in small masses to any point of disease in the endothelium and also to each other. This has been termed conglutination of the blood-plaques. Gradually the mass grows and subsequently leukocytes are added. These set on foot true fibrinformation or coagulation. White thrombi therefore consist of conglutinated plaques, leukocytes, and fibrin. They first appear as hyaline, viscid masses; but subsequently become granular from partial disintegration. If the circulation is alternately slow and more rapid, distinct layers are seen in the thrombus, first dark colored from admixture of red corpuscles, then lighter in hue. Such thrombi are called stratified. If the circulation is irregular from dilatation of the vessels or other causes, the light and dark areas of the thrombus may be more irregularly disposed.

The thrombus first formed is the primary thrombus. Subsequently it extends by additions (secondary thrombus) in the direction of the current of blood as far as the next collateral branch of the vein or artery, into which the thrombus frequently extends as a rounded prominence. In the case of the veins a new thrombus may start from such projection (Fig. 5), and eventually the clot

may extend as far as the heart. The thrombus may be lateralthat is, when it lies against the vessel-wall-or obstructive, when the lumen is completely obliterated. In the veins small thrombi are frequently formed in the valvular pouches in marantic subjects.

FIG. 7.-Branch of the brachial artery after amputation, showing vascularization of the thrombus, Th (Weber).

In the heart thrombi are especially common on diseased valves, in the auricular appendages, and in the intertrabecular spaces. They frequently appear as polypoid masses, and may be attached by slender pedicles. A curious form, called ball thrombi, is seen in the auricles. These are rounded clots wholly or almost wholly separated from the wall, and may occasion serious obstruction at the orifices of the heart.

Effects.-Frequently the collateral circulation is so quickly

established that no untoward results are seen. When a large vein is obstructed venous congestion and dropsy may follow; obstruction of an artery causes local anemia, and subsequently, if the collateral circulation is not established, degenerations or necrosis. Thrombotic obstruction of small arteries may cause hemorrhagic infarction. Embolism and general pyemia result from softening of the thrombus.

Subsequent Changes.-After their formation all thrombi contract. In this way the red forms may become light colored by extrusion of the red corpuscles. In small vessels red thrombi often become light colored by removal of hemoglobin and a species of hyalin-transformation. These may have the appearances of white thrombi and are only distinguished by careful examination.

After the thrombus has contracted it may undergo various degenerative changes. Frequently the white corpuscles, plaques, and fibrin are broken down into an emulsion by liquefactionnecrosis and fatty degeneration, and the red corpuscles converted into granular pigmented masses. These softened portions are swept into the circulation and occasion embolism. Frequently this form of simple softening occurs in the center of large thrombi and gives rise to cyst-like formations (Fig. 6).

A more serious form of softening occurs when the thrombus is infected by micro-organisms. In this case true purulent softening takes place, and the wall of the blood-vessel shares largely in the suppurative processes. This form occurs especially in the thrombi blocking blood-vessels of suppurating or necrotic tissues. General pyemia and infectious embolism result.

A more favorable termination of a thrombus is calcification. This is most frequent in the clots in dilated veins, the calcareous

thrombi being known as phleboliths. Arterioliths and cardioliths are rarely met with.

Organization of the thrombus may result from the irritation it occasions. New blood-vessels and proliferating connective-tissue cells spring from the vasa vasorum and lining membrane of the blood-vessel as well as from endothelial cells covering the thrombus, and penetrate the thrombus (Fig. 7). From these organization proceeds as elsewhere, and as it advances the thrombus itself is absorbed. Finally, the clot is fully replaced by connective tissue enclosing a small amount of blood-pigment or calcified remains of the thrombus. The blood-vessel may be converted into a solid fibrous cord, or may be distorted and narrowed by bands of connective tissue in the interior. Sometimes after partial vascularization of a thrombus small vessels running parallel with the lumen of the obstructed vessel become dilated and thus partly reestablish the channel. This is termed canalization of the thrombus (Fig. 8). In other cases canalization may begin as a process of simple softening.

EDEMA.

Definition. The term edema is applied to a condition in which the liquid within the tissues is increased in quantity.

Etiology. It is primarily necessary to understand the methods by which the liquids normally present in the tissues escape from the blood-vessels, their original source.

Several processes are concerned in this escape of fluid. In the first place, the pressure of the blood serves to cause a certain amount of direct filtration, just as liquid enclosed in tubes of permeable animal-membrane escapes when the pressure outside is less than within. In this process of direct filtration the state of the tissues themselves plays a part. If the normal elasticity of the tissues and degree of pressure of the liquid in the interstitial spaces are lowered, liquid escapes through the capillary-walls to equalize the pressure. A second process at work is that known as diffusion or osmosis. In this there is an exchange between the blood and the tissue-liquids, certain substances being taken into the blood in exchange for water and other constituents of the blood-plasma. The liquid thus discharged from the blood-vessels enters into the metabolic activity of the tissues to a greater or less degree, is somewhat altered in character, and the surplus is carried off in the lymphatic capillaries as lymph. Certain physiologists (Heidenhain et al.) believe that there is a farther and very important factor of a vital sort. This is described as an active secretory function of the endothelial cells of the capillaries and lymphatic spaces; so that, according to this view, lymph-formation is in a measure at least a direct secretion. This view, though not generally accepted, is supported by many facts.

Briefly, then, lymph-formation may be described as the escape of water and other substances through a more or less permeable membrane, the capillary-walls, in consequence of direct filtration, osmosis, and probably secretion. The quantity present in the tissues depends upon the quantity escaping from the blood-vessels and the amount carried away by the lymphatic circulation.