quoted in the section on Digestion (p. 322), where a brief account will also be found of the origin and physiological significance of the different constituents.

The Quantity of Bile Secreted.-Owing to the fact that a fistula of the common bile-duct or gall-bladder may be established upon the living animal and the entire quantity of bile be drained to the exterior without serious detriment to the animal's life, we possess numerous statistics as to the daily quantity of the secretion formed. Surgical operations upon human beings (see p. 321 for references), made necessary by occlusion of the bile-passages, have furnished similar data for man. In round numbers the quantity in man varies from 500 to 800 cubic centimeters per day, or, taking into account the weight of the individuals concerned, about 8 to 16 cubic centimeters for each kilogram of body-weight. Observations upon the lower animals indicate that the secretion is proportionally greater in smaller animals. This fact is clearly shown in the following table, compiled by Heidenhain' for three herbivorous animals:

There seems to be no doubt that the bile is a continuous secretion, although in animals possessing a gall-bladder the secretion may be stored in this reservoir and ejected into the duodenum only at certain intervals connected with the processes of digestion. The movement of the bile-stream within the system of bile-ducts—that is, its actual ejection from the liver, is also probably intermittent. The observations of Copeman and Winston on a human patient with a biliary fistula showed that the secretion was ejected in spirts, owing doubtless to contractions of the muscular walls of the larger bile-ducts. But though continuously formed within the liver-cells, the flow of bile is subject to considerable variations. According to most observers the activity of secretion is definitely connected with the period of digestion. Somewhere from the third to the fifth hour after the beginning of digestion there is a very marked acceleration of the flow, and a second maximum at a later period, ninth to tenth hour (Hoppe-Seyler), has been observed in dogs. The mechanism controlling the accelerated flow during the third to the fifth hour is not perfectly understood. It would seem to be correlated with the digestive changes occurring in the intestine, but whether the relationship is of the nature of a reflex nervous act, or whether it depends on increased blood-flow through the organ or upon some action of the absorbed products of secretion remains to be determined. It has been shown that the presence of bile in the blood acts as a stimulus to the liver-cells, and it is highly probable that the absorption of bile from the intestine which occurs during digestion serves to accelerate the secretion; but this circumstance obviously does not account for the marked increase observed in animals with biliary fistulas, since in these cases the bile does not reach the intestine at all. Therapeutically various substances have been stated by different authors to act as true cholagogues-that is, to stimulate the 1 Hermann's Handbuch der Physiologie, Bd. v. Thl. 1, S. 253.

secretion of bile. Of these substances the one whose action is most undoubted is bile itself or the bile acids. When given as dried bile, in the form of pills, a marked increase in the flow is observed.'

Relation of the Secretion of Bile to the Blood-flow in the Liver.— Numerous experiments have shown that the quantity of bile formed by the liver varies more or less directly with the quantity of blood flowing through the organ. The liver-cells receive blood from two sources, the portal vein and the hepatic artery. The supply from both these sources is probably essential to the perfectly normal activity of the cells, but it has been shown that bile continues to be formed, for a time at least, when either the portal or the arterial supply is occluded. However, there can be little doubt that the material actually utilized by the liver-cells in the formation of their external and internal secretions is brought to them mainly by the portal vein, and that variations in the quantity of this supply influences directly the amount of bile produced. Thus, occlusion of some of the branches of the portal vein diminishes the secretion; stimulation of the spinal cord diminishes the secretion, since, owing to the large vascular constriction produced thereby in the abdominal viscera, the quantity of blood in the portal circulation is reduced; section of the spinal cord also diminishes the flow of bile or may even stop it altogether, since the result of such an operation is a general paralysis of vascular tone and a general fall of bloodpressure and velocity; stimulation of the cut splanchnic nerves diminishes the secretion because of the strong constriction of the blood-vessels of the abdominal viscera and the resulting diminution of the quantity of the blood in the portal circulation; section of the splanchnics alone, however, is said to increase the quantity of bile, in dogs, since in this case the paralysis of vascular tone is localized in the abdominal viscera. The effect of such a local dilatation of the blood-vessels would be to diminish the resistance along the intestinal paths, and thus lead to a greater flow of blood to that area and the portal circulation.

In all these cases one might suppose that the greater or less quantity of bile formed depended only on the blood-pressure in the capillaries of the liver lobules that so far at least as the water of the bile is concerned it is produced by a process of filtration and rises and falls with the blood-pressure. That this simple mechanical explanation is not sufficient seems to be proved by the fact that the pressure of bile within the bile-ducts, although comparatively low, may exceed that of the blood in the portal vein.

The Existence of Secretory Nerves to the Liver.-The numerous experiments that have been made to ascertain whether or not the secretion of bile is under the direct control of secretory nerves have given unsatisfactory results. The experiments are difficult, since stimulation of the nerves supplying the liver, such as the splanchnic, is accompanied by vaso-motor changes which alter the blood-flow to the organ and thus introduce a factor that in itself influences the amount of the secretion. So far as our actual knowledge goes, the physiological evidence is against the existence of secretory nerve1 Journal of Experimental Medicine, 1897, vol. ii. p. 49.

fibres controlling the formation of bile. On the other hand, there are some experiments, although they are not perfectly conclusive, which indicate that the glycogen formation within the liver-cells is influenced by a special set of glyco-secretory nerve-fibres. This fact, however, does not bear directly upon the formation of bile.

Motor Nerves of the Bile-vessels.-Doyon 2 has recently shown that the gall-bladder as well as the bile-ducts is innervated by a set of nerve-fibres comparable in their general action to the vaso-constrictor and vaso-dilator fibres of the blood-vessels. According to this author, stimulation of the peripheral end of the cut splanchnics causes a contraction of the bile-ducts and gall-bladder, while stimulation of the central end of the same nerve, on the contrary, brings about a reflex dilatation. Stimulation of the central end of the vagus nerve causes a contraction of the gall-bladder and at the same time an inhibition of the sphincter muscle closing the opening of the common bile-duct into the duodenum. These facts need confirmation, perhaps, on the part of other observers, although they are in accord with what is known of the actual movement of the bile-stream. The ejection of bile from the gallbladder into the duodenum is produced by a contraction of the gall-bladder, and it is usually believed that this contraction is brought about reflexly from some sensory stimulation of the mucous membrane of the duodenum or stomach. The result of the experiments made by Doyon would indicate that the afferent fibres of this reflex pass upward in the vagus, while the efferent fibres to the gall-bladder run in the splanchnics and reach the liver through the semilunar plexus.

Normal Mechanism of the Bile-secretion.-Bearing in mind the fact that our knowledge of the secretion of bile is in many respects incomplete, and that any description of the act is therefore partly conjectural, we might picture the processes concerned in the secretion and ejection of bile as follows: The bile is steadily formed by the liver-cells and turned out into the bile-capillaries; its quantity varies with the quantity and composition of the blood flowing through the liver, but the formation of the secretion depends upon the activities taking place in the liver-cells, and these activities are independent of direct nervous control. During the act of digestion the formation of bile is increased, owing probably to a greater blood-flow through the organ and to the generally increased metabolic activity of the liver-cells occasioned by the inflow of the absorbed products of digestion. The bile after it gets into the bile-ducts is moved onward partly by the accumulation of new bile from behind, the secretory force of the cells, and partly by the contractions of the walls of the bile-vessels. It is stored in the gall-bladder, and at intervals during digestion is forced into the duodenum by a contraction of the muscular walls of the bladder, the process being aided by the simultaneous relaxation of a sphincter-like layer of muscle that normally occludes the bile-duct at its opening into the intestine; both these last acts are under the control of a nervous reflex mechanism.

1 Morat and Dufourt: Archives de Physiologie, 1894, p. 371.

2 Archives de Physiologie, 1894, p. 19; see also Oddi: Arch. ital. de Biologie, t. xxii., cvi.

In a very interesting research by Bruno' it has been shown that the actual passage of bile into the intestine is occasioned, reflexly no doubt, by the passage of the chyme from stomach to intestine. As long as the stomach is empty no bile flows into the duodenum; the flow commences when the stomach begins to empty its contents into the intestine, and ceases as soon as this process is completed. The author endeavored to ascertain the substances in the chyme that serve as the stimulus in this reaction. As far as his experiments go, they show that fats and the digested products of proteids (peptones and proteoses) are the most efficient stimuli. Acids, alkalies, and starch or the substances formed from it during salivary digestion are ineffective. Presumably the fats and the products of proteid digestion act on the sensory fibres of the duodenal membrane.

Effect of Complete Occlusion of the Bile-duct.-It is an interesting fact that when the flow of bile is completely prevented by ligation of the bileduct, the stagnant liquid is not reabsorbed by the blood directly, but by the lymphatics of the liver. The bile-pigments and bile-acids in such cases may be detected in the lymph as it flows from the thoracic duct. In this way they get into the blood, producing a jaundiced condition. The way in which the bile gets from the bile-ducts into the hepatic lymphatics is not definitely known, but possibly it is due to a rupture, caused by the increased pressure, at some point in the course of the delicate bile-capillaries.

KIDNEY.

Histology. The kidney is a compound tubular gland. The constituent uriniferous tubules composing it may be roughly separated into a secreting part comprising the capsule, convoluted tubes, and loop of Henle, and a collecting part, the so-called straight collecting-tube, the epithelium of which is assumed not to have any secretory function. Within the secreting part the epithelium differs greatly in character in different regions; its peculiarities may be referred to briefly here so far as they seem to have a physiological bearing, although for a complete description reference must be made to some work on Histology.

The arrangement of the glandular epithelium in the capsule with reference to the blood-vessels of the glomerulus is worthy of special attention. It will be remembered that each Malpighian corpuscle consists of two principal parts, a tuft of blood-vessels, the glomerulus, and an enveloping expansion of the uriniferous tubule, the capsule. The glomerulus is a remarkable structure (see Fig. 65, 4). It consists of a small afferent artery which after entering the glomerulus breaks up into a number of capillaries, which, though twisted together, do not anastomose. These capillaries unite to form a single efferent vein of a smaller diameter than the afferent artery. The whole structure, therefore, is not an ordinary capillary area, but a rete mirabile, and the physical factors are such that within the capillaries of the rete there must be a greatly diminished velocity of the blood-stream, owing to the great increase 1 Archives des sciences biologiques, 1899, t. vii. p. 87.