and may, though somewhat imperfectly, contribute to the subsequent restoration of the degenerated parts.

In regard to the blood vessels, great stress has of late been laid upon the alteration of their walls, for the reason that this is the starting point of the most important stage of inflammation, viz., exudation. It is, unfortunately, not yet possible to give any comprehensive and satisfactory idea of the inner condition of an inflamed blood vessel wall. Since the endothelia of the blood vessels are rightly looked upon as the fixed cells of the connective tissue, which shut off the parenchyma of the body from the blood, we may question how far the changes in the blood vessel walls may be compared to the above described process in the fixed connective tissue corpuscles. There appears, indeed, to be a certain sponginess in the blood vessel walls, which is coinciIdent with the retraction of the offshoots of the network of the lymphoid cells.

Arnold and Thoma have almost demonstrated the presence of interstices in the cement-substance of the capillaries in all acute inflammations. Cell division and increase of protoplasm have been observed in chemical inflammations. But with all this the main difficulty remains unsolved. This is the more to be regretted as the alteration of the blood vessel walls determines the future course of the inflammation. Its immediate effect is the dilatation and engorgement of the blood vessels; in other words, inflammatory hyperæmia. To this is joined that escape of the constituents of the blood, known as inflammatory exudation, which is more or less permanent and especially important as an anatomical product of the inflammatory process.

(b) INFLAMMATORY HYPEREMIA.-In order to gain a correct understanding of inflammatory hyperæmia, we shall do well to entirely disregard the current ideas about arterial and venous hyperemia and their origin. The blood vessels must be considered, not as constituents of the circulatory apparatus, but as constituents of the inflamed parenchyma. If it be true, as no one now doubts, that inflammatory hyperemia is really produced by parenchymatous changes, it may safely be called parenchymatous hyperæmia. It appears, aside from all other features, that the cohesion of the blood vessel walls is diminished in inflammation. Diminished cohesion is indicated, at least, by the above mentioned yielding of the blood vessel wall

to the blood pressure, the dilatation and hyperæmization of the circulation.

The process may easily be followed under the microscope; best of all in the mesentery of a living curarized frog, which has been carefully stretched over a cork ring. In ten or fifteen minutes after the operation, the widening of the blood vessels begins. This reaches its maximum in one or two hours, and continues so during the entire process. Two hours later the dilatation is followed by a perceptible slowing of the blood current. When we consider that no obstacle is offered by the veins to the flow of blood, and that the arteries do not hinder the blood from coursing, as in arterial hyperæmia, more swiftly through the enlarged capillaries, we must regard this retarded flow as an especially characteristic mark of inflammatory hyperæmia.

The slowing of the blood current can lead to a temporary or even complete blood stoppage (stasis). The local dilatation of the blood vessels is not a sufficient explanation of this proceeding. Local dilatation of the blood vessels also occurs in arterial hyperæmia, which, of itself, does not retard the flow in a smaller blood vessel. We must, therefore, revert again to the alterations in the blood vessel walls. It is this factor which changes the whole power of diffusibility between the blood and parenchyma into a heightened exosmotic current. With a force foreign to normal nutrition, all the blood particles are drawn toward the blood vessel wall, and thus, among other things, the velocity of their forward movement is diminished. I say "among other things," because inflammatory exudation is a far-reaching and important result of abnormal exosmosis.

(c) INFLAMMATORY EXUDATION.-By inflammatory exudation we understand the escape of the constituents of the blood from the blood vessels of the inflamed tissues and parenchyma. The visible result is either an infiltration of the parenchyma with the escaped material, or external discharges.

All exudates are composed of different constituents of the blood, such as salt, water, albumen, fibrinoplastic substance, and blood corpuscles. In proportion as an exudate contains more of one or the other of the above named substances, it is called serous, fibrinous, corpuscular or hemorrhagic.

The serous exudate is closely allied in composition to the normal nutritive juices, except that the latter, while nutrition

remains undisturbed, is quickly taken up by the parenchyma, which needs nourishment; whereas, the serous exudate accumulates, because the normal channels of exit are insufficient to carry off an exudate thrown out with such rapidity and abundance. There always remains, however, the possibility of disposing of it through the normal channels of exit. This generally occurs without delay as soon as the effect of the inflammatory irritation subsides, so that the serous exudate is, on the whole, of a fleeting and temporary character.

Serous exudate is, only in rare instances, the culmination of an inflammation. It is usually the forerunner of more intense inflammation, or it encircles a smaller territory where a higher degree of exudation is found, viz., suppuration. It is customary in such cases to call it "inflammatory oedema."

Finally, the serous exudate is found to be an important factor in inflammations of the skin, of the mucous, serous and other membranes. As the structure of these organs is unfavorable to an internal deposit of an exudate, the serous discharge seeks the neighboring free surfaces, where it appears in the form of an albuminous secretion, which can likewise act as a vehicle for the migratory cells which exist in the parenchyma of the skin.

The fibrinous exudate resembles, in composition, a spontaneously coagulated, albuminous body, which bears so striking a resemblance to blood fibrin that we are tempted to consider them as one and the same, and imagine that, in a fibrinous exudation, the denser fibrinoplastic substance leaves the blood vessels with the blood serum, and afterward hardens. This hardening, we know, needs the intervention of a second substance derived from cells. This is furnished, according to Alexander Schmidt, by the colorless blood corpuscles. The white blood corpuscles which escape at the same time with the fibrinous exudate, may take upon themselves the formation of this "fibrin ferment." This is corroborated by the histological examination of the much feared croupous membrane found on the surface of the larynx and trachea. Here, the fibrinous exudate forms a network, in whose meshes round cells are lodged, as though coagulation had centred about the cell.

The exudate itself achieves, by reason of its coagulation, a certain anatomical independence. When seen in large quantities, as in the sero-fibrinous exudation of the pleura, pericardium, etc., the fibrin appears to the naked eye as a

yellowish-white, soft, porous substance, which, upon pressing out the moisture, is reduced to a body at least twentyfold smaller, but tough, thick, and inelastic. It forms shreds and flakes, occasionally also, fibres, which entwine themselves in the infiltrated meshes of the porous connective tissue, or are stretched between the surfaces of the serous sacs. The microscope shows us here fine twisted filaments, interwoven into the most delicate meshes, then, again, tough, flattened bands, which form a network, or unite into fenestrated membranes. These appearances have given rise to the term fibrin. Fibrin also occurs in the form of a granular coagulation. This appearance in the blood has given rise to much misapprehension,* because the granular bodies are here seen in a more isolated form, while in fibrinous exudates they are often massed together in an indescribable variety of shapes.

It is self apparent that the eventual removal of the fibrinous exudate is more complex than that of the serous. Even when it is present on free surfaces, as in croupous inflammations of the mucous membranes and lung parenchyma, it adheres firmly, and a certain time must elapse before the process of separation sets in. Still more, where there is a deposit of fibrin in the enclosed spaces of the body, or even in the meshes of the areolar connective tissue, is a previous chemical metamorphosis essential to its liquefaction and reabsorption. In the majority of cases, the fibrin is transformed, along with a separation of fat globules, into a sodic albuminate, which is soluble, and may even be absorbed through the walls of the blood vessels by osmosis.

It is a mistaken idea that fibrin can organize, that is, change into real connective tissue fibres. Whenever connective tissue is found in the place formerly occupied by fibrinous exudate, this connective tissue has invariably been produced from the corpuscular constituents of the exudate.

Corpuscular exudate consists either entirely of cells, or to such an extent that the occasional serous and fibrinous admixture is subordinate. These cells are originally protoplasmic masses, destitute of walls, but containing nuclei, and having amoeboid motion. They cannot be distinguished from the other mobile cells of the vascular and connective tissue apparatus, viz., the colorless blood corpuscles, lymph corpuscles,

* Zimmermann's elementary corpuscles, Leidesdorf's syphilitic corpuscles, etc.

The

protoplasmic cells, etc. Experimental study of corpuscular exudation has shown that the great majority of these cells are either simply migrated colorless blood corpuscles, or are derived from subdivision of the same. The process of escape is best seen in the mesentery of a living frog. individual blood corpuscles, as is well known, may be recognized in the veins, and here it is that they present to the observer an unusually characteristic appearance. The peripheral zone of the blood current, the original blood plasma, becomes filled with countless colorless blood corpuscles, which adhere to the wall and finally form a simple and uninterrupted layer of globular cells upon the entire inner surface of the blood vessel. This is the beginning of the migratory process. Small, colorless, button-like elevations arise on the outside of the venous wall, as if the blood vessel wall itself had produced outgrowths. By slow degrees the projections increase in size till they lie on the blood vessel like hemispheres, about half the size of white blood corpuscles. The hemisphere changes gradually into a pear-shaped body, with the large end turned away from the blood vessel, and the pointed extremity attached to its wall. The periphery of the pear-shaped body now begins to send out delicate prolongations and ramifications, and the once smooth surface becomes uneven and indented. The main body of the corpuscle recedes more and more from the blood vessel wall, and we see finally a colorless, glistening, contractile body, a wandering connective tissue cell, which is nothing more or less than a migrated colorless blood corpuscle. An individual cell often occupies more than two hours in completing this process, and as the same phenomena are taking place simultaneously, at numberless other points, it is not easy to observe a single cell in all the stages of the process.

This active amoeboid movement, this restless creeping forward of the migrated colorless blood corpuscles, contrasts sharply with the passive rôle which they enact in the circulating blood. Their inclination to adhere to each other and to all stationary points, which was formerly called their cohesiveness, but is now recognized as an outcome of their amoeboid mobility, is, without doubt, overcome by the same power which, in one moment, mingles the masses of blood in the heart, and in the next scatters it in a thousand directions.