millimeters. power in Digestive

per cent.

Acidity in

Quantity in cubic centi

0.576

0.528

meters.

MILK,

600 c.c.

MEAT,
100 gr.

BREAD,

100 gr.

to the intensity of the appetite or enjoyment of the food, and may last for several hours even though the actual period of eating has been short (five minutes). It is this secretion that first acts upon the food received into the stomach. Later its action is supplemented by an augmented secretion, caused by stimuli of a chemical nature originating in the food ingested. Some foods contain substances ready formed that are capable of acting in this way. Investigation of various articles of diet showed that meat extracts, juices, and soups contain these substances in largest amounts. Milk and aqueous solutions of gelatin act in the same way, although less powerfully. Water also, if in sufficient quantity, acts as a direct stimulant. Other common articles of food, such as bread or white of egg, do not contain these stimulating substances. Food of the latter character, when introduced directly into a dog's stomach through a fistula, provokes not a drop of secretion and undergoes no digestion, if it has been introduced in such a way as to avoid arousing the psychical secretion, as, for instance, at times when the animal is dozing. If, however, this latter class of foods undergo digestion, as would happen in normal feeding in consequence of the action of the "psychical secretion," substances capable of stimulating the stomach to secretion are developed, and their action keeps up the flow of secretion after the effect of the psychical factor has become weakened. The nature of these chemical stimuli remains entirely undetermined. Pawlow's first statement that peptone constituted at least one member of this group he now finds is erroneous. It is assumed that these substances act through the secretory nerves, and it has been shown also that other substances may have the contrary effect of retarding or inhibiting the gastric secretion. This has been proved for fats at least. Oils of various kinds decrease the secretion of gastric juice, while they augment the pancreatic secretion. Another most suggestive result of Pawlow's work is the proof that the quantity and characteristics of the secretion vary with the food. Apparently the quantity of the secretion varies, other

VOL. I.-16

0.480

0.432

18

0.384

16

0.336

11

0.288

12

By

conditions being the same, with the amount of the food to be digested. some means the apparatus is adjusted in this respect to work economically. Different kinds of food produce secretions varying not only as regards quantity, but also in their acidity and digestive action. The secretion produced by bread, though less in quantity than that caused by meat, possesses a greater digestive action. On a given diet the secretion will assume certain characteristics, and Pawlow is convinced that further work will disclose the fact that the secretion of the stomach is not caused normally by general stimuli all affecting it alike, but by specific stimuli contained in the food or produced during digestion, whose action is of such a kind as to produce the secretion best adapted for the food ingested.

One of the curves showing the effect of a mixed diet (milk, 600 cubie centimeters; meat, 100 grams; bread, 100 grams) upon the gastric secretion, as determined by Pawlow's method, is reproduced in Fig. 63. It will be noticed that the secretion began shortly after the ingestion of the food (seven minutes), and increased rapidly to a maximum that was reached in two hours. After the second hour the flow decreased rapidly and nearly uniformly to about the tenth hour. The acidity rose slightly between the first and second hours, and then fell gradually. The digestive power showed an increase between the second and third hours.

Histological Changes in the Gastric Glands during Secretion. The cells of the gastric glands, especially the so-called chief-cells, show distinct changes as the result of prolonged activity. Upon preserved specimens taken from dogs fed at intervals of twenty-four hours, Heidenhain found that in the fasting condition the chief-cells were large and clear, that during the first six hours of digestion the chief-cells as well as the border-cells increased in size, but that in a second period extending from the sixth to the fifteenth hour, the chief-cells became gradually smaller, while the border-cells remained large or even increased in size. After the fifteenth hour the chief-cells increased in size, gradually passing back to the fasting condition (see Fig. 64).

Langley has succeeded in following the changes in a more satisfactory way by observations made directly upon the living gland. He finds that the chief-cells in the fasting stage are charged with granules, and that during digestion the granules are used up, disappearing first from the base of the cell, which then becomes filled with a non-granular material. Observations similar to those made upon the pancreas demonstrate that these granules represent in all probability a preliminary material from which the gastric enzymes are made during the act of secretion. The granules, therefore, as in the other glands, may be spoken of as zymogen granules, the preliminary material of the pepsin being known as pepsinogen and that of the rennin sometimes as pexinogen.

Glands of the Intestine.-At the very beginning of the intestine in the immediate neighborhood of the pylorus is found a small area of mucous membrane containing distinct tubular glands, known usually as the glands of 1 Journal of Physiology, 1880, vol. iii. p. 269.

Brunner. These glands resemble closely in arrangement those of the pyloric end of the stomach, with the exception that the tubular duct is more branched. The secreting cells are similar to those of the pyloric glands of the stomach. Little is known of their secretion. According to some authors it contains pepsin. The amount of secretion furnished by these glands would seem to be too small to be of great importance in digestion. Throughout the length

FIG. 64.-Glands of the fundus (dog): A and A', during hunger, resting condition; B, during the first stage of digestion; C and D, the second stage of digestion, showing the diminution in the size of the "chief" or central cells (after Heidenhain).

of the small and large intestine the well-known crypts of Lieberkühn are found. These structures resemble the gastric glands in general appearance, but not in the character of the epithelium. The epithelium lining the crypts is of two varieties-the goblet cells, whose function is to form mucus, and columnar cells with a characteristic striated border. The changes in the goblet cells during secretion and the probability of a relationship between them and the neighboring epithelial cells has been discussed (see p. 216). Whether or not the crypts form a definite secretion has been much debated. Physiologists are accustomed to speak of an intestinal juice, "succus entericus," as being formed by the glands of Lieberkühn, but practically nothing is known as to the mechanism of the secretion. The succus entericus itself, however it may be formed, can be collected by isolating small loops of the intestine and

bringing the ends to the abdominal wall to form fistulous openings. The secretion thus obtained contains diastatic and also inverting ferments, the action of which is described on p. 308. Histologically, the cells in the bottom of the crypts do not possess the general characteristics of secreting cells.

D. LIVER; KIDNEY.

The liver is a gland belonging to the compound tubular type. The hepatic cells represent the secretory cells and the bile-ducts carry off the external secretion, which is designated as bile. In addition it is known that the liver-cells occasion important changes in the material brought to them in the blood, and that two important compounds, namely, glycogen and urea, are formed under the influence of these cells and afterward are given off to the blood-stream. The liver, then, furnishes a conspicuous example of a gland that forms simultaneously an external and an internal secretion. this section we have to consider only certain facts in relation to the external secretion, the bile.

In

Histological Structure. The general histological relations of the hepatic lobules need not be repeated in detail. It will be remembered that in each lobule the hepatic cells are arranged in columns radiating from the central vein, and that the intralobular capillaries are so arranged with reference to these columns that each cell is practically brought into contact with a mixed blood derived in part from the portal vein and in part from the hepatic artery.

As a gland making an external secretion, the relations of the liver-cells to the ducts and to the nervous system are important points to be determined. The bile-ducts can be traced without difficulty to the fine interlobular branches running round the periphery of the lobules, but the finer branches or bilecapillaries springing from the interlobular ducts and penetrating into the interior of the lobules have been difficult to follow with exactness, especially as to their connection with the interlobular ducts on the one hand, and with the liver-cells on the other. The bile-capillaries have long been known to penetrate the columns of cells in the lobule in such a way that each cell is in contact with a bile-capillary at one point of its periphery, and with a blood-capillary at another, the bile- and blood-capillaries being separated from each other by a portion of the cell-substance. But whether or not intracellular branches from these capillaries actually penetrate into the substance of the liver-cells has been a matter in dispute. Kuppfer contended that delicate ducts arising from the capillaries enter into the cells and end in a small intracellular vesicle. As this appearance was obtained by forcible injections through the bile-ducts, it was thought by many to be an artificial product; but recent observations with staining reagents tend to substantiate the accuracy of Kuppfer's observations and confirm the belief that normally the system of bile-ducts begins within the liver-cells in minute channels that connect directly with the bilecapillaries.

Two questions with reference to the bile-ducts have given rise to considerable

discussion and investigation: first, the relationship existing between the livercells and the lining epithelium of the bile-ducts; second, the presence or absence of a distinct membranous wall for the bile-capillaries. Different opinions are still held upon these points, but the balance of evidence seems to show that the bile-capillaries have no proper wall. They are simply minute tubular spaces penetrating between the liver-cells and corresponding to the alveolar lumen in other glands. Where the capillaries join the interlobular ducts the livercells pass gradually or abruptly, according to the class of vertebrates examined, into the lining epithelium of the ducts. From this standpoint, then, the livercells are homologous to the secreting cells of other glands in their relations to the general lining epithelium. Several observers (MaCallum,' Berkley, and Korolkow3) have claimed that they are able to trace nerve-fibres to the liver-cells, thus furnishing histological evidence that the complex processes occurring in these cells are under the regulating control of the central nervous system. According to the latest observers (Berkeley, Korolkow) the terminal nerve-fibrils end between the liver-cells, but do not actually penetrate the substance of the cells, as was described in some earlier papers. If these observations prove to be entirely correct they would demonstrate the direct effect of the nervous system on some at least of the manifold activities of the livercells. So far as the formation of the bile is concerned we have no satisfactory physiological evidence that it is under the control of the nervous system.

Composition of the Secretion.-The bile is a colored secretion. In most carnivorous animals it is golden red, while in the herbivora it is green, the difference depending on the character and quantity of the pigments. In man the bile is usually stated to follow the carnivorous type, showing a reddish or brownish color, although in some cases apparently the green predominates. The characteristic constituents of the bile are the pigments, bilirubin in carnivorous bile and biliverdin in herbivorous bile, and the bile acids or bilesalts, the sodium salts of glycocholic or taurocholic acid, the relative proportions of the two acids varying in different animals. In addition there is present a considerable quantity of a mucoid nucleo-albumin, a constituent which is not formed in the liver-cells, but is added to the secretion by the mucous membrane of the bile-ducts and gall-bladder; and small quantities of cholesterin, lecithin, fats, and soaps. The inorganic constituents comprise the usual salts-chlorides, phosphates, carbonates and sulphates of the alkalies or alkaline earths. Iron is found in small quantities, combined probably as a phosphate. The secretion contains also a considerable though variable quantity of CO, gas, held in such loose combination that it can be extracted with the gas-pump, without the addition of acid. The presence of this constituent serves as an indication of the extensive metabolic changes occurring in the liver-cells. Quantitative analyses of the bile show that it varies greatly in composition even in the same species of animal. Examples of this variability are given in the analyses

1 MaCallum: Quarterly Journal of the Microscopical Sciences, 1887, vol. xxvii. p. 439. "Berkley: Anatomischer Anzeiger, 1893, Bd. viii. S. 769. 3 Korolkow: Ibid., S. 750.