IV. SECRETION.

A. GENERAL CONSIDERATIONS.

THE term secretion is meant ordinarily to apply to the liquid or semiliquid products formed by glandular organs. On careful consideration it becomes evident that the term gland itself is widely applied to a variety of structures differing greatly in their anatomical organization—so much so, in fact, that a general definition of the term covering all cases becomes very indefinite, and as a consequence the conception of what is meant by a secretion becomes correspondingly extended.

Considered from the most general standpoint we might define a gland as a structure composed of one or more gland-cells, epithelial in character, which forms a product, the secretion, that is discharged either upon a free epithelial surface such as the skin or mucous membrane, or upon the closed epithelial surface of the blood- and lymph-cavities. In the former case —that is, when the secretion appears upon a free epithelial surface communicating with the exterior, the product forms what is ordinarily known as a secretion; for the sake of contrast it might be called an external secretion. In the latter case the secretion according to modern nomenclature is designated as an internal secretion. The best-known organs furnishing internal secretions are the liver, the thyroid, and the pancreas. It remains possible, however, that any organ, even those not possessing an epithelial structure, such as the muscles, may give off substances to the blood comparable to the internal secretions-a possibility that indicates how indefinite the distinction between the processes of secretion and of general cell-metabolism may become if the analysis is carried sufficiently far. If we consider only the external secretions definition and generalization become much easier, for in these cases the secreting surface is always an epithelial structure which, when it possesses a certain organization, is designated as

a gland. The type upon which these secreting surfaces are constructed is illustrated in Figure

46. The type consists of an

FIG. 46.-Plan of a secreting membrane.

epithelium placed upon a basement membrane, while upon the other side of the membrane are blood-capillaries and lymph-spaces. The secretion is derived ultimately from the blood and is discharged upon the free epithelial surface, which is supposed to communicate with the exterior. The mucous membrane of the alimentary canal from stomach to rectum may be considered,

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if we neglect the existence of the villi and crypts, as representing a secreting surface constructed on this type. If we suppose such a membrane to become

FIG. 47. To illustrate the simplest form of a tubular and a racemose or acinous gland.

invaginated to form a tube or a sac possessing a definite lumen (see Fig. 47), we have then what may be designated technically as a gland.

It is obvious that in this case the gland may be a simple pouch, tubular or saccular in shape (Fig. 48), or it may attain a varying degree of complexity by the elongation of the involuted portion and the development of side branches

(Fig. 49). The more complex structures of this character are known sometimes as compound glands, and are further described as tubular, or racemose (saccular), or tubulo-racemose, according as the terminations of the invaginations are tubular, or saccular, or intermediate in shape. As a matter of fact we find the greatest variety in the structure of the glands imbedded in the cutaneous and mucous surfaces, a variety extending from the simplest form of crypts or tubes to very complicated organs possessing an anatomical independence and definite vascular and nerve-supplies as in the case of the salivary glands or the kidney. In compound glands. it is generally assumed that the terminal portions of the tubes alone form the secretions, and these are designated as the the acini or alveoli, while the tubes connecting the alveoli with the exterior are known as the ducts, and it is supposed that their lining epithelium is devoid of secretory activity.

The secretions formed by these glands are as varied in composition as the glands are in structure. If we neglect the case of the so-called reproductive

1 Flemming has called attention to the fact that most of the so-called compound racemose glands, salivary glands, pancreas, etc., do not contain terminal sacs or acini at the ends of the system of ducts; on the contrary, the final secreting portions are cylindrical tubes, and such glands are better designated as compound tubular glands.

glands, the ovary and testis, whose right to the designation of glands is doubtful, we may say that the secretions in the mammalian body are liquid or semiliquid in character and are composed of water, inorganic salts, and various organic compounds. With regard to the last-mentioned constituent the secretions differ greatly. In some cases the organic substances present are not found in the blood, and furthermore they may be specific to a particular secretion, so that we must suppose that these constituents at least are produced in the gland itself. In other cases the organic elements may be present in the blood, and are merely eliminated from it by the gland, as in the case of the urea found in the urine. Johannes Müller long ago made this distinction, and spoke of secretions of the latter kind as excretions, a term which we still use and which carries to our minds also the implication that the substances so named are waste products whose retention would be injurious to the economy. Excretion as above defined is not a term, however, that is capable of exact application to any secretion as a whole. Urine, for example, contains some constituents that are probably formed within the kidney itself, e. g., hippuric acid; while, on the other hand, in most secretions the water and inorganic salts are derived directly from the blood or lymph. So, too, some secretions-for example, the bile-carry off waste products that may be regarded as mere excretions, and at the same time contain constituents (the bile salts) that are of immediate value to the whole organism. Excretion is therefore a name that we may apply conveniently to the process of removal of waste products from the body, or to particular constituents of certain secretions, but no fundamental distinction can be made between the method of their elimination and that of the formation of secreted products in general. Owing to the diversity in composition of the various external secretions and the obvious difference in the extent to which the glandular epithelium participates in the process in different glands, a general theory of secretion cannot be formulated. The kinds of activity seem to be as varied as is the metabolism of the tissues in general.

It was formerly believed that the formation of the secretions was dependent mainly if not entirely upon the physical processes of filtration, osmosis, and diffusion. The basement membrane with its lining epithelium. was supposed to constitute a membrane through which various products of the blood or lymph passed by filtration and diffusion, and the variation in composition of the secretions was referred to differences in structure and chemical properties of the dialyzing membrane. The significant point about this view is that the epithelial cells were supposed to play a passive part in the process ; the metabolic processes within the cytoplasm of the cells were not believed to affect the composition of the secreted product. As compared with this view the striking peculiarity of modern ideas of secretion is, perhaps, the importance attributed to the living structure and properties of the epithelial cells. It is believed generally now that the glandular epithelium takes a direct part in the production of some at least of the constituents of the secretions. The reasons for this view will be brought out in detail further on in describing the secreting processes of the separate glands. Some of the general facts, how

ever, which influenced physiologists in coming to this conclusion are as follows:

Microscopic examination has demonstrated clearly that in many cases parts of the epithelial cell-substance can be followed into the secretion. In the sebaceous secretion the cells seem to break down completely to form the material of the secretion; in the formation of mucus by the goblet cells of the mucous membrane of the stomach and intestines a portion of the cytoplasm after undergoing a mucoid degeneration is extruded bodily from the cell to form the secretion; in the mammary glands a portion of the substance of the epithelial cells is likewise broken off and disintegrated in the act of secretion, while in other glands the material of the secretion is deposited within the cell in the form of visible granules which during the act of secretion may be observed to disappear, apparently by dissolution in the stream of water passing through the cell. Facts like these show that some at least of the products of secretion arise from the substance of the gland-cells, and may be considered as representing the results of a metabolism within the cell-substance. From this standpoint, therefore, we may explain the variations in the organic constituents of the secretions by referring them to the different kinds of metabolism existing in the different gland-cells. The existence of distinct secretory nerves to many of the glands is also a fact favoring the view of an active participation of the gland-cells in the formation of the secretion. The first discovery of this class of nerve-fibres we owe to Ludwig, who (in 1851) showed that stimulation of the chorda tympani nerve causes a strong secretion from the submaxillary gland. Later investigations have demonstrated the existence of similar nerve-fibres to many other glands-for example, the lachrymal glands, the sweat-glands, the gastric glands, the pancreas. Recent microscopic work indicates that the secretory fibres end in a fine plexus between and around the epithelial cells, and we may infer from this that the action of the nerve-impulses conducted by these fibres is exerted directly upon the gland-cells.

The formation of the water and inorganic salts present in the various secretions offers a problem the general nature of which may be referred to appropriately in this connection, although detailed statements must be reserved until the several secretions are specially described. The problem involves, indeed, not only the well-recognized secretions, but also the lymph itself as well as the various normal and pathological exudations. Formerly the occurrence of these substances was explained by the action of the physical processes of filtration, diffusion, and osmosis through membranes. With the blood under a considerable pressure and with a certain concentration in salts on one side of the basement membrane, and on the other a liquid under low pressure and differing in chemical composition, it would seem inevitable that water should filter through the membrane and that processes of osmosis and diffusion should be set up, further changing the nature of the secretion. Upon this theory the water and salts in all secretions were regarded merely as transudatory products, and so far as they were concerned the epithelium was supposed to act

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simply as a passive membrane. This theory has not proved entirely acceptable for various reasons. It has been shown that living membranes offer considerable resistance to filtration even when the liquid pressure on one side is much greater than on the other. Tigerstedt and Santessen, for instance, found that a lung taken from a frog just killed gave no filtrate when its cavity was distended by liquid under a pressure of 18 to 20 centimeters, provided the liquid used was one that did not injure the tissue. If, however, the lungtissue was killed by heat or otherwise, filtration occurred readily under the same pressure. In some glands, also, the formation of the water and salts, as has been said, is obviously under the control of nerve-fibres, and this fact is difficult to reconcile with the idea that the epithelial cells are merely passive filters. In glands like the kidney, and in other glands as well, it has not, as yet, been shown conclusively that the amount of water and salts increases in proportion to the rise of blood-pressure within the capillaries, as should happen if filtration were the sole agent at work; and furthermore, certain chemical substances when injected into the blood may increase the flow of urine to an extent that it is difficult to explain by the use of the filtration and diffusion theory alone.

While, therefore, it cannot be denied that the anatomical conditions prevailing in the glands are favorable to the processes of filtration and osmosis, and while we are justified in assuming that these processes do actually occur and serve to account in part for the appearance of the water and inorganic salts, it seems to be clear that in the present condition of our knowledge theories based on these factors alone do not suffice to explain all the phenomena connected with the secretion of water and salts. Until the contrary is definitively proved we may suppose that the epithelial cells are actively concerned in the process. The way in which they act is not known; various hypotheses have been advanced, but none of them meets all the facts to be explained, and at present it is customary to refer the matter to the vital properties of the cells-that is, to the peculiar physical or chemical properties connected with their living structure.

We may now pass to a consideration of the facts known with regard to the physiology of the different glands considered merely as secretory organs. The functional value of the secretions will be found described in the sections on Digestion and Nutrition.

B. MUCOUS AND ALBUMINOUS (SEROUS) TYPES OF GLANDS; SALIVARY GLANDS.

Mucous and Albuminous Glands.-Heidenhain recognized two types of glands, the mucous and the albuminous, basing his distinction upon the character of the secretion and upon the histological appearance of the secreting cells. The classification as originally made was applied only to the salivary glands and to similar glands found in the mucous membranes of the mouth

1 Mittheil. vom physiol. Lab. des Carol. med.-chir. Instituts in Stockholm, 1885.