contrary, may form large cystic collections with thin, flattened walls. Colloid degeneration may be accompanied by serous transudation, due probably to vascular disturbances. The serous transudation seems to dissolve the colloid material, so that finally the cysts form compartments filled with a chocolate-colored fluid containing pus, blood, and crystals of cholesterin, sodium chlorid, and calcium oxalate (Fig. 17).

Microscopically the material is found in the glandular acini, in the cells, and in the connective tissues. There are often signs of pressure, and, probably from the same cause, the areas are anemic and have a poor vascular supply. The arrangement is usually in balls or whorls, homogeneous as a rule, but often with concentric or radiating lines. The areas often intercommunicate, and extensions may be traced into the adjacent tissues. The cells usually show degenerative changes, and inflammatory reactions are often present. Crystals of calcium oxalate are common. Acid stains are usually elected, as in hyaline degeneration. The indefiniteness of the reactions may make it impossible to exclude hyaline and mucoid changes.

Pathologic Physiology.-This is obscure, but seems to be analogous to that of mucoid change. The substance is undoubtedly produced in loco.

Colloid is a grave degeneration, usually connected with marked cellular disturbances. The substance may become hyaline or mucoid, or may be replaced by a simple or purulent exudation.

GLYCOGENIC INFILTRATION.

Definition. This condition consists in the presence of glycogen in cells which normally contain none, or the presence of an excess in cells which normally contain it, as in the liver, cartilage, muscles, leukocytes, in the embryo in all tissues, and in the uterus. The attempt has been made to separate glycogenic infiltration from a glycogenic degeneration, but the conversion of protoplasmic proteid into glycogen has never been demonstrated.

Etiology. The condition is not infrequent. It is seen in the tissues in diabetes, especially in the kidneys, muscles, liver, and circulating leukocytes. It occurs in neoplasms, especially in malignant growths of mesoblastic origin, being rare in most carcinomata. In leukocytosis of different varieties the cells may contain an excess, and granules of the glycogen may float free in the plasma. In purulent collections and in inflammatory areas the cells may be markedly infiltrated. The infectious granulomata, however, seem exempt. The amylaceous bodies of the prostate are closely allied to glycogen.

Pathologic Anatomy.-Tissues rich in glycogen may present a hyaline appearance; usually there are no macroscopic alter

ations. Microscopically the material is generally found within. the cells; it may, however, be in the intercellular substance, and may be free in the plasma of blood or the fluid of exudates. It is commonly deposited as round balls, which may be concentrically striated. In fresh tissues it is soluble in water, but loses its solubility after fixation by alcohol, etc.

Glycogen is stained brown by iodin, but the brown is not turned blue on the application of sulphuric acid. Ptyalin or amylopsin converts it into sugar, with the loss of the color-reaction."

The pathologic physiology is obscure. In diabetes it is simply an expression of the general hyperglycemia. In neoplasms and suppurations the collections are probably depositions.

DROPSICAL INFILTRATION.

By dropsical infiltration is meant edema of the cells, the presace in cells of an excess of plasma. This does not always occur

FIG. 18.-Dropsical infiltration of the epithelial cells of a carcinoma of the breast: a, ordinary epithelial cells; b, dropsical cells; c, dropsical nuclei; d, enlarged nucleoli (Ziegler).

in general dropsy, the fluid being between the cells and often compressing them to a marked degree. In other instances the cells take up the fluid. In burns and pemphigus and in other skin-lesions connected with vesiculation, and in various inflammations of organs, edema of the cells occurs. It is also a part of the degeneration termed cloudy swelling.

The cells are enlarged, often to an extreme degree, and they may even burst. The protoplasm sooner or later becomes cloudy and often presents degenerative changes-fatty metamorphosis in particular. Vacuolation is frequently observed (Fig. 18).

The condition is probably a purely physical phenomenon in the dropsies. In the cutaneous lesions other factors are operative.

CALCIFICATION.

Definition. Calcification consists in the abnormal deposition in tissues of earthy salts. The phosphates and carbonates of calcium are the chief salts concerned, the oxalates, however, are often present; and the corresponding magnesium salts may be mixed with them. The best physiologic examples are the senile change in the vascular apparatus and the formation of the brain-sand (acervulus cerebri). Calcification of the skeletal tissues is usually accomplished as a physiologic process through the activities of special cells; this is an essential element in ossification.

Local

Etiology. The deposition generally occurs in diseased tissues, especially in those the seat of vascular disorders. necrosis or fibrosis antedates intercellular calcification, and the process may be accompanied by atrophy and absorption of certain cellular elements. In neoplasms abnormal cellular conditions certainly predispose; but here, too, the vascular relations are of notable importance. Hyaline and fatty degenerations often precede or accompany calcification.

In rare instances no local predispositions can be determined. Cases of this kind occur in old age, and in these cases it is inferred that, owing to increased lime-resorption from the skeleton, the system is saturated to the point of precipitation (metastatic calcification). Similar supersaturation of the blood with calcareous matter may occur in cases of extensive disease of bones, and may lead to widespread deposition.

Pathologic Anatomy.-Early in the process no macroscopic signs are apparent. On microscopic examination the salts are seen as fine granules scattered through the intercellular substance. Cellular infiltration, however, is not uncommon, and in such instances the cells show more or less extensive nuclear and protoplasmic degenerations. By the coalescence of the granules larger, irregularly spherical bodies may be formed. These usually have a concentric arrangement (psammoma bodies). Definite crystals are rare, but may be seen. The next adjacent tissue may present an opaque appearance. In certain localities, especially the blood-vessels and serous membranes, calcareous plates are formed. The depositions may attain a surprising size, especially in the vessels and in neoplasms. The color of the deposits is usually white, grayish, or yellow; accidental pigments may, however, produce discolorations. On staining the deposition takes up both carmine and hematoxylin, but exhibits no elective attraction for the anilin dyes. The salts are dissolved by acids, best by hydrochloric acid; in the case of carbonates, with evolution of carbonic acid gas. Many organic and inorganic acids are employed in the decalcification of tissues for purposes of microscopic study. Fibrosis, cellular necroses, and degenerations can be demonstrated in the tissues by suitable methods.

Seats. It is in the cardiovascular system that the condition is of the most importance. It often occurs as a simple senile change, usually connected with an atrophy of the elastic tissues of the vessel-walls, hyaline degeneration of the connective tissue, and general fibrosis. It is almost invariably an accompaniment of sclerotic endocarditis and arteriosclerosis. In the endocardium the valves are most frequently affected; of the vessels, the aorta, the coronary arteries, and the cerebral vessels. The process is, however, often universal, and the splanchnic vessels and radial arteries. seem very susceptible. It affects chiefly the intima and media. In the pericardium the deposition is uncommon without the previous occurrence of pericarditis; in adherent pericardium the heart may be literally enclosed in a calcified sac. In the myocardium calcification is usually interfibrillar, but may involve the fibers. Large collections may occur in the pituitary body, the meninges, and in the ventricular plexuses. It is common in the joints, uncommon in the pleura, rare in the peritoneum. In the muscles local formations are not rare, and usually occur at the seat of previous injury or irritation. In the lungs and liver it is not unusual in and around foci of necrosis due to various causes (tuberculosis, parasites, etc.). Cicatricial tissue often becomes calcified. In the walls of cysts, in the biliary and urinary bladders, in the limiting wall of old abscesses and hematomata, in thromboses, and even in cutaneous scars calcification is a common incident. In the kidneys infarcts of these salts may be formed. The neoplasms most subject are the avascular tumors: uterine fibromata, fibromata in general, dermoid cysts, goiters, scirrhous carcinomata, tumors of the pituitary bodies, and especially neoplasms involving bones or cartilages. It may, however, occur in the most vascular sarcomata. special term psammoma (q. v.) is applied to certain calcified neoplasms. Lithopedia are the calcified fetuses of extra-uterine pregnancy. Apart from neoplasms, the most striking intracellular depositions are seen in the ganglion-cells in areas of softening and in the renal cells following certain metallic poisonings (mercury). It is interesting to note that the intestinal epithelium, which normally secretes the larger part of the lime-salts discharged from the body, is rarely infiltrated by them.

The

Pathologic Physiology.-Various views are held to explain the depositions. An excess of the salts in the blood or tissueliquids must be rare. On the one hand, it has been assumed that the soluble are converted into insoluble salts, and, on the other hand, that the tissues have become less solvent for the salts. Probably the best established view is that the salts are precipitated as insoluble combinations with proteids.

Calcareous deposits are probably never removed, but once formed remain permanently. There is no doubt that they influence the adjacent tissues, causing degenerations.

OSSIFICATION.

Ossification implies the deposition of lime-salts and other changes through the agency of osteoblastic cells. It occurs in cartilages, and in tumors connected with the bones, cartilages, and periosteum. The salts are regularly deposited and are usually in masses between the cells. An accurate differentiation from calcification can in some instances be made only by the detection of osteoblasts after decalcification of the material.

URATIC INFILTRATION.

Deposits of urate of sodium in the cartilages and fibrous tissues of joints and in various other situations occur in the course of gout (see Disturbances of Metabolism and Diseases of Joints).

PIGMENTATION.

According to the origin and variety of the pigments, pigmentations may be divided into four groups: 1, those in which the pigments are derived from external sources; 2, those derived from the hemoglobin; 3, those derived from the bile; 4, those derived from cellular activity within the organism.

Pigmentation from the Exterior.

Of the first group, those caused by entrance of foreign bodies through the air-passages are the most important. The condition now generally termed pneumonokoniosis is commonly a disease of occupation. Coal, iron, and stone are the most frequent foreign substances inhaled. Vegetable particles, as grain-dust and textile fibers, and animal hairs and furs are not uncommonly the cause of such pigmentations. Corresponding to the agent, there are such terms as anthracosis (coal-dust pigmentation), siderosis (iron), calcicosis (stone), etc. (Fig. 19). Inhaled substances probably do not reach the alveoli, but are caught by the bronchial cellular cilia. In part they are coughed up or otherwise cast off with the bronchial secretions; in part they penetrate the bronchial walls or are carried by phagocytic cells into the submucosa (Fig. 20). They may become deposited in the latter situation, or may be carried in the lymphatic circulation to the peribronchial and mediastinal glands, the fibrous tissue of the lung, or the subpleural tissues. In rare instances the pigment finally reaches the general circulation, following which it is deposited largely in the spleen, liver, intestinal mucosa, and kidneys. In these cases the mucous membranes from the lips downward may be more or less pigmented.

Pigmentation through the alimentary tract is best illustrated by argyria following the excessive ingestion of soluble salts of silver. The depositions seem to consist of a reduced form of a