Epithelium is a tissue which exhibits varying degrees of vitality in different parts according to its function; thus the outer portions of the epidermis are almost entirely non-protoplasmic, and they undergo few physical and chemical changes of any kind; their function is simply protective. In the secreting glands, on the other hand, the epithelial cells are composed of protoplasm which is the seat of the most active and remarkable chemical operations, the building up of new substances which are discharged as a secretion to fulfil important functions elsewhere; or the substances may be simply taken from the circulating fluid by the cells, and poured out from them to form an excretion: that is, these substances are simply got rid of and discharged from the body by this means.

A secreting epithelium may be considered as a partition between the blood, or, more properly speaking, the lymph, on the one side, and the lumen of the secreting gland on the other. From the lymph the materials are taken by the secreting cells and then worked up into the components of the secretion, and finally discharged on the other side into the lumen, and thence by the ducts of the secreting gland to their destination.

A useful contrast is drawn by Dr. McKendrick 2 between the activities of three important varieties of organs :

1 The amount of chlorides in the urine is correspondingly low.

2 Physiology, vol. i. pp. 484-5.

(1) Muscles. (2) Electrical organs. (3) Secreting cells.

If a be contraction, b electromotive phenomena, and c metabolic or chemical changes in a muscle a is large, b and c relatively small; in an electrical organ, a is apparently absent, b is large, and c relatively small; and in secreting cells a does not occur as an active contraction, though the cell may slowly change in form and bulk, b occurs, but is comparatively small, while c is relatively large. Thus the differences between these three varieties of protoplasm are very largely differences of degree only. A further resemblance to be briefly noted is, that just as muscles are supplied with nerves along which motor impulses are conveyed, and electrical organs with special nerves, excitation of which causes activity of the organs they supply, so secreting cells are in many cases at least supplied with nerves, excitation of which causes the activity of the gland cells they supply; and in some cases where a gland receives two nerves with different functions, excitation of one will produce a secretion differing somewhat from that produced by exciting the other.

The amount of secretion is in some cases, as in that of the kidney, very largely influenced by the amount of blood reaching the organ, and by the blood pressure; this again is dependent on the size of the blood vessels, which is regulated by the vaso-motor nerves that supply their muscular tissue.

In most cases the secreting cells that line the acini of a secreting gland are large spheroidal or polyhedral cells. In other cases, as in the convoluted tubules of the kidney of some animals (possibly the epithelium of the cerebro-spinal cavity must be included here), the cells are ciliated.

No histological differences can be made out in certain glands according to the secreting activity of the cells; instances of such glands are the kidneys and the sweat glands; these are glands that are excretory in function, they form no special ferment for use elsewhere, and their activity depends very largely on the amount of blood passing to them.

There are, however, certain other cases in which a distinct difference between the active and resting condition of the secreting cells can be made out. We have, in fact, already studied the changes in one instance, namely, the formation of mucin in ciliated and columnar cells. A similar transformation of protoplasm into mucin (or mucinogen, as it is called while still within the cells) is seen in the acini of the numerous little racemose mucous glands of the mouth, pharynx, trachea, and oesophagus, as well as in the cells of the mucous alveoli of the submaxillary and sublingual salivary glands. The cells distended with

G G

granules of mucinogen disintegrate, extruding mucin, and their place is then taken by protoplasmic cells which were formerly pressed against the basement membrane by the swollen mucigenous cells, forming the darkly staining demilunes. These protoplasmic cells undergo in time the same mucoid degeneration.

In the case of the sebaceous glands and the mammary gland, the secreting cells become swollen with fat-globules; it is, in fact, a fatty degeneration of the protoplasm, the cells disintegrate, and the secretion is filled with the minute fat-globules thus liberated. In the milk secreted during the first few days after lactation commences, some of the secreting cells filled with fat-globules may be readily discovered, but later these colostrum corpuscles, as they are termed, are not found, the disintegration of the cells taking place entirely in the alveoli of the mammary gland. In other cases still, secretion does not involve either complete or partial destruction of the secreting cells themselves, but nevertheless the changes occurring during secretion are distinctly

FIG. 72.-Alveoli of Serous Gland. A, at rest: B, after a short period of activity; C, after a prolonged period of activity. (Langley.)

visible to the microscope. As instances, the parotid gland, the pancreas, and the central cells of the gastric glands may be mentioned. In the inactive condition of these glands, the cells are seen to be packed full of distinct granules which obscure their nuclei. The granules are imbedded in the protoplasm of the cells, and the latter almost completely fill the alveoli, scarcely any lumen being perceptible (fig. 72 A). After a short period of activity the granules (which may be seen either in the perfectly fresh condition of the gland, or by staining with osmic acid) disappear from the outer part of the cells, the inner part being distinctly granular, and some granules being apparently free within the lumen of the alveolus which is now becoming distinct (fig. 72 B). With more prolonged activity, such as is produced by a dose of pilocarpine, the clear outer zone increases in extent, and the granules are found only at the free border of the cells (fig. 72 C). The nuclei become distinct and the cells smaller; they now, moreover, being composed chiefly of non-granular protoplasm, stain readily with carmine. According to

Heidenhain and Langley 2 the three processes-growth of the clear protoplasm, conversion into granules, and discharge of these into the lumen-are all proceeding simultaneously in different parts of the cell during activity. The material which thus accumulates within the cell is not, however, the same as that which appears in the secretion; the most important constituent of the secretion is the zyme or ferment, and the granules are either composed of, or indicate the presence of, a zymogen, or ferment precursor. The zymogen differs somewhat in its properties from the ferment, but is converted into the ferment with great readiness; pepsinogen in the stomach cells, and trypsinogen in the pancreatic cells, may be mentioned as instances of zymogens.

In the case of the pancreas it has, however, been shown that the granules which have been usually identified with the zymogen may occur in the absence of zymogen. In animals from whom food has been withheld for longer than twenty-four hours, glycerine fails to extract any ferment from the pancreas; but microscopic examination shows that the cells are still filled with granules. The conclusion must therefore be drawn either that these granules are something different from those ordinarily seen, or that the granules are not themselves the zymogen, but only the carriers of it. Under ordinary circumstances, however, the presence of granules indicates the presence of the zymogen; and zymogen without granules has never been observed (Levascheff3).

In most cases the secretion when formed passes into the cavity lined by the secreting epithelium. In some cases, however, as in the liver (and the same has been seen after forcible injection in the pancreas also), the secretion collects in vacuoles in the secreting cells from which it passes into the smallest ducts by means of intracellular canaliculi.4

COMPOUND EPITHELIA

In the case of the transitional epithelium of the bladder and ureters, the stratified epithelium of the cornea and oesophagus, the cells are apparently composed of simple protoplasm with nuclei. But in the stratified epithelium which forms the epidermis, and to a less extent in that lining the interior of the mouth, the surface layers of cells (those which form the horny layer) have their protoplasm replaced by keratin or horny material. In the nails, horns, and hoofs,

32.

1 Studien d. phys. Inst. zu Breslau, 1868.

2 Journ. of Physiology, 1879; Phil. Trans. 1881.

5 Levascheff worked under Heidenhain's superintendence. Pflüger's Archiv, xxxvii. 4 Quain's Anatomy,

632, 638.

this conversion into keratin is still more marked, and in addition there is a deposit of calcareous salts, especially calcium phosphate. In hairs and feathers also the chief organic constituent is keratin ; cells filled with fat or pigment granules may occur in the medullary portions of the hair. In both hair and feathers silica has been described as a constant and important mineral constituent (27-40 per cent. of the ash; von Bibra); iron may also occur.

The deeper portions of stratified epithelia, which become horny in their surface layers, remain protoplasmic; in the skin the protoplasmic layers (Malpighian layer) and the horny layers proper are separated by two thin layers, the stratum granulosum and the stratum lucidum. The granules in the former layer are composed of a substance which stains deeply with carmine (Langerhans'). It is termed eleidin, and is supposed to be an intermediate condition in the replacement of protoplasm by keratin. In the cells of the Malpighian layer, granules of a dark pigment called melanin are found; these are especially abundant in the skin of negroes. The cells of the epidermis have a small amount of cementing substance between them, which, like the ground substance of connective tissue, dissolves in weak alkalis; and by such treatment the cells may be separated from one another.

2

Keratin

Keratin or horny material belongs to the class of substances that are called albuminoids. It is exceedingly insoluble, and can be freed from other substances by treating cuticle, hair, hoofs, nails, &c. with ether, alcohol, water, and dilute acids. A very similar substance called neurokeratin can be obtained from nervous structures, these being, like the epidermis, epiblastic in origin.

It is not affected by boiling with water; but when heated with water in closed vessels to 150°-200° C. it forms a turbid solution. It is not affected by weak acids in the cold, but is dissolved by boiling glacial acetic acid; it is decomposed by boiling with mineral acids, yielding with sulphuric acid products very similar to those obtained from proteids, viz. leucine, tyrosine, aspartic acid, and volatile fatty acids. Like proteids also it gives off when burnt the same peculiar odour.

Elementary analyses, from their close resemblance one to another, seem to point to the fact that keratin is a chemical unit, but as in

1 Archiv f. mikr. Anat. 1873.

2 The dark pigment deposited in the skin in cases of Addison's disease is apparently

of the same nature.