existence and degree of congestion, pigmentation, or jaundice, will obviously alter the color. The areas of degeneration may be uniform or isolated. In the heart and liver particularly streaks or irregular areas may produce a mottled appearance. On section free fat may drip from the knife and cut surface; in other cases

FIG. 12.-Fatty degeneration of the epithelium of the renal tubules; stained with osmic acid (Simmonds).

no fat-droplets can be seen macroscopically. In rare instances fat-crystals may be visible to the naked eye.

Microscopic Appearances.-The parenchyma-cells are first and most extensively affected, though the connective tissue may become involved. The cells are usually somewhat enlarged. The natural granules of the protoplasm disappear, and in their stead are fine dark granules, which usually stain black with osmic acid (Figs. 12, 13), and which are dissolved by alcohol, ether, etc., but not by acetic acid. A peculiar reaction of the granules is their staining with fuchsin (fuchsinophile granules). Usually the granules are very fine and only slightly refractile; they may, however, be large, and considerable droplets may appear or the entire cell become one large fatFIG. 13.-Fatty de- drop, as in fatty infiltration. The nuclei in many cases of moderate degree show no changes; later in the process, however, the chromatin becomes diffused and refuses to stain and the nucleus may entirely disappear. Large hyalin balls may form inside the cells; these stain with acid-stains. The cell-membrane sooner or later breaks down,

and the fatty contents and detritus fill the space. Cholesterin, lecithin, and fatty crystalline formations are often seen.

Seats.-Fatty degeneration occurs in nearly all tissues. The epithelial structures, especially the liver and kidneys, the heartmuscle, and the central nervous organs are the tissues most frequently affected. As before stated, interstitial as well as parenchymatous tissues may be involved. The cellular constituents of exudates and transudates are also liable to the change, and the liquid may thus present the appearance of an emulsion.

Pathologic Physiology. The manner of occurrence of fatty metamorphosis is as yet entirely obscure. If it were proved that fats can be formed out of proteids, this fact would warrant the simple explanation that in fatty degeneration the protoplasmic proteid is directly converted into fat. Certain evidence of this has, however, never been presented, and our reactions for fat are too unreliable to warrant deductions from simple microscopic studies. It has become apparent that the old and still largely accepted physiologic theory has never been demonstrated, even though it be true. No one has as yet produced fat in an animal fed on proteids entirely freed from fats and carbohydrates, and in the experiments with meats which contain both it has not been shown that any carbon-retention was unaccompanied by nitrogen-retention and that the carbon was retained in the form of fats or glycogen. It is, of course, quite possible that the proteids may be directly converted into fat, and in recent experiments upon starving frogs poisoned with phosphorus this was apparently demonstrated; but even in these experiments it is likely that the glycogen of the liver was the source of the fat produced.

Unlike fatty infiltration, fatty degeneration tends to cell-death, as must in the nature of things be obvious, for it is an expression of cell-disease. Mild grades with the preservation of the nuclei undoubtedly admit of recovery; severe grades go on to total necrobiosis. The function of the cells is, of course, disturbed. This may be in the direction of simple reduction of function, or it may cause distinctly abnormal activity with pathologic metabolic products.

THE ALBUMINOID DEGENERATIONS.

The amyloid, hyaline, mucoid, and colloid degenerations reprep resent proteid metamorphoses which are closely related. In typical instances they can be quite clearly differentiated from each other, and for the sake of clearness and convenience they will be separately described. It must be understood, however, that the products are closely related substances whose chemical characteristics and relations are not clear, and which cannot in many cases be distinguished.

AMYLOID DEGENERATION.

Definition. This consists in the appearance in tissues of amyloid material; whether formed in loco or deposited is not quite clear. Amyloid seems to be a combination of chondratin-sulphuric acid with a proteid.

Etiology.-The common conditions under which amyloid degeneration arises are suppuration and ulceration. In tuberculosis, especially of the lungs and skeleton, and particularly in cases of mixed infection, and in syphilitic ulceration are found the conditions most favorable to its production. It occurs, however, in

FIG. 14.-Amyloid degeneration of the kidney, showing amyloid substance in the walls of the blood-vessels of the glomerulus at b, and hyaline tube-casts in the renal tubules at g (Ziegler).

ulcerations of various sorts, in cutaneous ulcerations, in gastroenteritis, in connection with neoplasmic necrosis, in actinomycosis. Rarely it occurs under conditions of cachexia without suppuration, as in cancer, malaria, leukemia. In a few instances it occurs without any apparent cause.

Local amyloid formations are probably in no wise connected with the general condition and undoubtedly are often entirely physiologic.

Pathologic Anatomy.-In marked instances the organs are enlarged, and their specific gravity increased. On section the tissue is firm; the cut surface is smooth and neither contracts nor

extrudes. The consistency varies with the coexistence and degree of fibrosis, fatty degeneration, etc. Amyloid substance is more inelastic than any other degenerative material. The color of the organ is usually pale, but may obviously be altered by congestion, pigmentation, or fatty degeneration. The amyloid substance itself has a glistening, waxy, translucent appearance which is almost pathognomonic. This waxy appearance is not always uniform. Mild or even moderate degeneration may not present macroscopic appearances; in fact, apparently quite normal tissues may be highly amyloid microscopically. The special appearances in various organs will be described in the appropriate chapters.

Microscopic Appearances.-The favorite seats are the intima and media of the blood-vessels, the adventitia being rarely affected, the endothelium apparently never. The fixed connective tissues of the organs are the parts affected, the wandering cells and leukocytes being rarely involved. Muscle-cells are undoubtedly susceptible; but recent studies seem to show that glandular and lining epithelium is never involved. Such cells may, and often do, show fatty or other degenerations or necrosis, but the presence of amyloid substance within their protoplasm has not been shown. The substance appears as irregular clumps or streaks in the interstitial tissues, often compressing the cells and blood-vessels. It presents a glistening homogeneous appearance. The cells usually present evidences of atrophy and other degenerations. In the renal glomeruli and in the Malpighian corpuscles of the spleen the appearances are perhaps most distinctive. Without staining amyloid degeneration cannot always be distinguished from other degenerations; indeed, not always with staining reactions. The substance is highly resistant to bacterial decomposition and to digestion.

Reactions (see also below).-The gentian-violet reaction seems to be the most invariable. In sections of tissue fixed for microscopic study gentian-violet colors the normal tissues blue; the amyloid substance is a light pink or red. Iodin-green gives a similar red reaction. A mahogany-red reaction with Lugol's solution of iodin is quite constant, but fails in the isolated amyloid bodies. It is easily obtained in fresh specimens. The red color is changed to a blue by treating with sulphuric acid or chlorid of zinc.

Seats. In the order of frequency amyloid degeneration affects the kidney, liver, and spleen, then the larger blood-vessels, the intestinal mucosa, the lymph-glands, the skeleton, the adrenal bodies, and the heart. It rarely affects the pulmonary mucosa, the bladder and genitalia, the thyroid body, the voluntary muscles, and, apart from the local amyloid bodies, the nervous system or the integument.

Local Amyloid Formations.-These occur in the nervous system, especially in advanced years and in scleroses, grouped about the

blood-vessels, most marked in the posterior cord and in the brain; in the prostate gland; about inflammatory areas; in infarcts; in granulomata, especially syphilis; and in neoplasms. They present themselves as small round bodies which usually have a concentric arrangement resembling starch-granules. They do not usually present the typical amyloid reactions; often they react more like hyaline substance, and indeed the blood-vessels in their situation seem especially affected with hyaline change. The special appearances and reactions of the amyloid bodies of the nervous system will be described in connection with neuropathology.

Pathologic Physiology.-As stated, amyloid substance seems to be a combination of chondratin-sulphuric acid with a proteid. It is composed of hydrogen, nitrogen, carbon, and sulphur, and is insoluble in weak alkalies. Chondratinic acid is normally present in bones, cartilages, and elastic tissue. It seems to have been shown that an amyloid-like substance exists in the elastic coat of the blood-vessels-perhaps a different combination of chondratinic acid. Our present knowledge suggests that amyloid substance is not entirely abnormal, but rather an abnormal combination of normal substances. It seems to result from proteid alterations in connection with the pathologic processes already detailed. That bacterial influences are not necessary is suggested, though not proved, by the fact that amyloid change has been produced by long-continued aseptic suppuration induced by turpentine injections.

Amyloid substance cannot be removed, but does not of itself compromise life. It may become transformed into typical hyaline substance. Amyloid degeneration interferes with functional activity by pressure upon the parenchyma and by vascular disturbBy its situation in the blood-vessels it may occasion

ances.

thrombosis.

HYALINE DEGENERATION.

Definition. This is a retrogressive process consisting in the appearance of a homogeneous proteid substance of obscure nature. It is closely allied to amyloid, mucoid, and colloid degeneration, and can certainly pass into each of them. The hyaline change of epithelium of older authors is now by general consent classed as

a mucoid transformation.

Etiology.-Hyaline degeneration occurs under the following pathologic circumstances: in the muscles during infections and septic processes and following traumatism; in intoxications, as by lead; in interstitial hemorrhages and hematoma; in struma; in cicatrices; in the blood-vessels in old age, arteriosclerosis, or aneurysm; in all forms of arteritis, especially of the nervous system; in the endocardium and cardiac valves in all diseases affecting