Microscopically, the tissues in caseation show no cells preserving their staining-reactions; everything is converted into débris. Around the affected area is usually found a zone of coagulation, of inflammation, or both.

FIG. 26.--Large tubercle of the lung, showing cheesy necrosis in the center.

Tissues that have undergone caseation may be cast off, reabsorbed, or encysted; resolution is not possible. Calcification is a frequent termination.

FAT-NECROSIS.

This term is now used to designate a peculiar type of necrosis to which the fatty tissues are subject, and is distinct from ordinary fatty metamorphosis. In human beings it is seen almost exclusively in the abdomen, abdominal walls, and subperitoneal fat. In nearly all instances it appears in connection with pancreatic disease-cysts, tumors, obstruction to the duct, and the various forms of acute pancreatitis. In rare instances the pancreas has not seemed especially diseased. In one case I have seen of hypertrophic cirrhosis of the liver the omentum was affected, while the pancreas showed nothing but a moderate degree of fibrosis.

The affected areas are white in color, usually not larger than a pea; they may be soft or quite gritty. Inflammatory reaction may or may not surround them. On microscopic examination crystals of the fatty acids may be seen together with more abundant crystals of a combination of lime with the fatty acids. This combination, it appears, is not a primary feature in the necrosis, suggesting that the fatty acids are first set free and then unite with lime-salts. In experimental work by Hildebrand, Williams, and Flexner it seems to have been shown that the typical condition may be the result of direct action of the fat-splitting ferment

of the pancreatic secretion. It is certain, however, that in some cases of pancreatic cysts containing steapsin no fat-necrosis has occurred. Bacteria have been supposed by some to be the essential agents causing the change, but this has not been demonstrated.

HEMOLYSIS.

Hemolysis, or blood-destruction, is a term limited to the red cells, and indicates destruction of the cell with dispersion of its hemoglobin. (The causes and other features are described under Pigmentations and Diseases of the Blood.)

GANGRENE.

Definition.-Gangrene, formerly defined as the death of tissue en masse, is perhaps best defined as the putrefaction of areas of necrosis. It may be primary, when a particular bacterium produces a gangrenous inflammation as its direct result, as in malignant edema; or secondary, when saprophytic bacteria decompose an area already necrosed from other causes. It may be dry or moist, according to the location and supply of fluids. It may furthermore be circumscribed, progressive, or metastatic.

Primary gangrene constitutes a specific affection, or rather a number of specific affections. Malignant edema, infectious emphysema, and some forms of anthrax may be included in this group. In these conditions there is violent infective inflammation with practically immediate gangrene of the affected parts.

Secondary gangrene is more common, and the appearances are very varied. The essential condition is putrefaction of a necrosed area.

Dry gangrene is usually due to vascular disturbances. As a result of arterial obstruction it is seen in the extremities in senility, and following arterial embolism or thrombosis of whatsoever nature if the collateral circulation be insufficient to nourish the part. Freezing may produce a dry form of gangrene, the vessels being blocked by thrombosis. Ergotism causes dry gangrene as a rule; the same may be said of Raynaud's disease. Finally, dry gangrene may result from the moist form when putrefaction is slow and evaporation of the fluids occurs. The putrefactive processes in the dry type are not marked, and may cease entirely. Dry gangrene is generally circumscribed, and the end-result of a typical case is mummification. The color is usually dark, finally black; early it may be yellow or brown; rarely, the tissues are very pale. There is little toxic absorption in these cases.

Moist gangrene presents numerous varieties. It is rarely produced by arterial occlusion, but is the usual result of extensive venous occlusion. Internal emboli, as in the pulmonary arteries or veins or mesenteric arteries, not infrequently cause gangrene of this form. It also occurs in the lungs as a result of inspirational

or other pneumonias, abscess, neoplasms, bronchiectasis, and in diabetes. It is seen as a result of traumatism and pressure in severe contusions (especially with vascular injuries), in intussusception and strangulation of the bowel; as a result of torsion in movable kidneys, spleens, or tumors. It is frequent in the obstructed or strangulated vermiform appendix. Extensive moist gangrene of the extremities or other parts is not rare in connection with diabetes. The mucous membranes may become gangrenous as a result of various infections. A particular form is noma of the mouth and genitalia. It is seen as a rare condition in certain skin-diseases; and is not unusual in severe trophic lesions, as decubitus, cystitis, mal perforant, etc.

In moist gangrene the consistency of the part becomes progressively softer. There may be local or widespread emphysema. The color is usually dark brown, due to disorganized blood-pigment; the skin commonly becomes black, and is covered with blebs. About the area there may be a zone of coagulation-necrosis with vascular thrombosis; or a zone of inflammatory reaction which will produce a line of demarcation. In some cases, especially the diabetic, neither of these zones is formed.

The cells first succumb. The protoplasm and nuclei exhibit various evidences of degeneration, the nuclei disappearing and the cells becoming converted into granular detritus. Fat and the myelin-sheaths of nerve-fibers are reduced to free fat and fatty crystals. The muscle-cells lose their striations and become fragmented; the axis-cylinders of nerves fibrillate. Hemorrhages into the area are common, due either to erosion of vessels and expulsion of their thrombi by the pressure of the blood-current, or to a genuine hemorrhagic condition the result of toxemia. Connective tissue and elastic fibers resist longer than the cells, but finally become liquefied. The affected area contains crystals of pigment, fatty acids, cholesterin, leucin, tyrosin, phosphates, and carbonates. Ammonia, the fatty acids, indol and skatol, amins, sulphuretted hydrogen, carbonic acid, and other gases, usually of pronounced odor, are formed. There is more or less toxic absorption from these areas.

But two things can happen to an area of gangrene; it may progress and cause the death of the individual, or may become circumscribed. In dry gangrene and in the vascular forms of moist gangrene limitation is the rule; the other moist forms tend to be progressive. In the circumscribed form a line of demarcation is formed by inflammatory reaction, and the mass is finally cast off as a sphacelus or slough if the area be superficial, or encysted if the area be internal. The latter cases may be followed by reabsorption of the contents and calcification of the sac.

GENERAL PATHOLOGY OF CELLULAR NECROSIS.

The cell as an individual element is liable to pathologic processes of various kinds that merit brief consideration, apart from definite forms of tissue-degeneration and necrosis.

Etiology. The causes of cellular degeneration and necrosis are numerous, including mechanical, thermal, electrical, chemical, and vital (trophic) influences of various kinds. It is easy to demonstrate the influence of some of these causes in the unicellular organisms such as amebæ, and the changes thus produced may also be seen under proper conditions in the cells of the animal body.

Pathologic Anatomy.-The cell as a whole may show various forms of distortion, or internal change. Increased irritability and mobility of the protoplasm cause the projection of pseudopodia, and these may be separated from the body of the cell as rounded particles more or less resembling the original cell. This is easily demonstrable in red blood-corpuscles subjected to heat. Sometimes particles of the substances are discharged from the cell and vacuolations (expulsion-vacuoles) result. Certain influences, like cold, and metallic salts or other poisons, cause a reduced mobility and general contraction of the cell. Granular precipitation may at the same time occur within the protoplasm. In other cases solution of parts of the cellular protoplasm occurs, and vacuoles of varying size are thus produced. Similar changes have been discovered in the nuclei of the cells, but certain special forms of nuclear change require special mention.

Nuclear solution or hypochromatosis may occur as a process of gradual fading or disappearance. The nucleus becomes more and more pallid, and finally is indistinguishable.

Karyorrhexis is a form of nuclear fragmentation in which the chromatin of the nucleus becomes broken up into small particles.

Hyperchromatosis is a degenerated condition of the nucleus, involving the nuclear membrane in particular. The body of the nucleus becomes pale and finally quite colorless, while the periphery is much more apparent and thickened. With the further destruction of the nucleus and cell the pigment-particles arranged around the periphery of the nucleus may become scattered through the cell.

Pyknosis is the name used to designate degeneration of the cell and nucleus in which the protoplasmic substance of these structures becomes more dense and their size correspondingly decreased. The cells become darker and frequently densely granular. When the nucleus is affected this contraction may leave a vacant zone about it, so that the nucleus apparently lies within a vacuole.

POST-MORTEM ALTERATIONS.

Certain changes take place after death which may suggest in their appearances ante-mortem disease. It is therefore necessary to recognize these in post-mortem examinations. The most striking change is the rigidity or rigor mortis, which is due to a coagulation of the muscle-albumin or myosin. This occurs at different intervals, according to the cause and nature of death. Sometimes, as in deaths after electrical discharges, it occurs almost instantaneously; more commonly its beginning is delayed for some hours. After twenty-four or forty-eight hours the rigidity disappears. Occasionally irregular post-mortem contractions of the muscles take place, and distortions or even movements are thus produced.

Circulatory Phenomena.-As is noted elsewhere (see CONGESTION) the blood-vessels, especially the arteries, contract after death, and drive the blood into the capillaries and veins. It is then more or less free to sink to dependent parts through the influence of gravity, and in consequence the

lower parts of the organs and of the body in general are congested. This is particularly marked in the lungs, but occurs in practically all organs. The blood may remain entirely within the blood-vessels, but not rarely the coloring-matter diffuses itself through the tissues and causes pigmented areas (livores mortis) that may suggest ante-mortem bruises.

The blood in the heart and other vessels tends to coagulate, though in some cases this is long delayed and remains imperfect. Usually dark red clots are found in the cavities of the heart and in the large vessels. Yellowish fibrinous clots are less likely to be post-mortem, but more often occur in cases in which death has taken a lingering form.

Post-mortem Degeneration of Tissues. Some time after death the tissues may become macerated and putrefactive changes may occur. To a large extent these are due to invasion of micro-organisms. It has been found that during the terminal stages of disease various forms of infection (especially micrococcic) occur. This terminal infection is often the immediate cause of death, and it is also concerned in the post-mortem change in the tissues. Histologically, a striking peculiarity of such post-mortem change is the absence of evidences of reaction (cellular infiltration and proliferation), such as characterize the response of living tissues to irritation.

Post-mortem softening of the mucous membranes may be due to the action of the secretions. This is especially marked in the stomach, where it is common to observe a macerated condition of the mucosa of the posterior wall. In this case the gastric juice is the direct cause of the alteration in the mucous membrane.

CHAPTER V.

INFLAMMATION AND REGENERATION.

INFLAMMATION.

Definition.-By this name are designated the vascular, exudative, degenerative, and regenerative changes which occur in the living tissues as a result of irritation by chemical, mechanical, or thermal agents. No short definition contains the essence, for inflammation is by no means a simple process. It varies with the varying anatomical conditions or the vitality of the tissue involved, and with the intensity or nature of the irritant. Galen and his followers defined it by giving the cardinal symptoms: heat (calor), redness (rubor), pain (dolor), and swelling (tumor). To these may be added altered function (functio læsa).

Historical. The earliest conceptions of inflammation were those of a specific entity. Subsequently various theories were offered in explanation of the several phenomena or symptoms. First, the blood-vessels were supposed to be influenced through the nervous system (vascular theories). Next, it was taught that the inflammatory irritant excites proliferative changes in the tissues (thus giving rise to round cells), and that this stimulation of the cellular activity invites more blood to the part (hence the hyperemia). This was the cellular and attraction theory of Virchow. Others, notably Cohnheim, described the emigration of leukocytes from the