I. Physiological Relations

The substances which enter the liver through the portal vein consist of the products of digestion in the widest sense, namely, proteids including leucin and tyrosin, sugars, salts, a trace of fat, and abundant water. When we parted with the proteids in the duodenum, they were in the form of peptones; when we meet with them again in the vena portae, they have been transformed into ordinary serum albumen, apparently in the process of absorption. The sugars enter the liver partly unchanged, partly perhaps as derivatives-lactic and butyric acid. The proteids, sugars, water, salt, etc., will obviously be poured into the liver very abundantly during digestion. At the same time, there enters the liver through the hepatic artery a supply of oxygen which appears to be precariously limited, if we may judge by the size of the vessel. In the presence of this double supply, and in proportion to it, the hepatic cells display their special activity, and yield glycogen, urea, and bile. The urea and bile are carried off as such, the former by the hepatic veins to escape by the kidneys, the latter by the bowels. The glycogen has a less simple history. It accumulates in the liver cells, where it appears as a form of amyloid material specially adapted for storing up in an insoluble state the. sugar and part of the proteids. By this arrangement the blood and body generally are saved from being flushed with sugar after each meal, and the sugar itself is not wasted. Under the influence of a ferment the glycogen is gradually re-converted into some kind of sugar; the amount of amyloid material hydrated varying with the necessities of the system. This function is regulated by a nervous mechanism, having its centre in the medulla, with efferent and (presumably) afferent nerves.

Another point in connection with the liver to be carefully noted by the therapeutist is the circulation of the bile. The bile, having entered the bowel and mixed with the chyme, is not entirely evacuated by the faeces. On the contrary, its most important constituents, the biliary salts, are re-absorbed from the bowel and carried back to the liver, again to be secreted and reach the bowel. Thus the bile may be said to move in a circle, comprised by the bile ducts and gall bladder, the intestine, and the portal vein.

II. Pharmacodynamics

Although the liver is apparently so inaccessihle, we have great control over the influences under which its multiform activity is displayed.

(1) By means of the food we can completely interrupt the hepatic functions, or interfere with them at our pleasure. The amount of urea, the secretion of bile, the proportion of store glycogen in the liver, may be modified directly, within certain limits, by the amount of food allowed; and the urea and glycogen may he respectively made to vary with the relative proportion of nitrogenous and amylaceous constituents in the diet. The supply of oxygen which reaches the liver by means of bodily exercise, is equally under our control. The larger the volume of oxygen entering the liver, the more ready and complete will be the subtle processes of chemical composition and decomposition within it. We thus come to appreciate a fact of the first importance-that we can influence the liver through the medium of its supply. But we can do so in another way. We can tap, as it were, the channel of supply, the portal vein. The radicals of the portal vein in the rectum (superior hemorrhoidal) anastomose with the veins around the anus, and leeches applied to this part will drain blood from the portal system, and thus indirectly from the liver. Closely allied to bleeding in principle is hydragogue purgation, which diverts a quantity of water from the portal radicles in the intestinal wall, and secures its evacuation.

(2) The liver may be influenced through its products, by securing the proper disposal of the urea, bile, and glycogen. In the bodily organs, as in the practical arts, the rate of manufacture cannot be maintained unless the products be removed. We have seen, in the stomach, that digestion is arrested by accumulation of peptones amongst the food. In the like manner, an accumulation of urea, of bile, or of glycogen, in the system, interferes with the hepatic processes. Now, as we shall afterwards see, we can increase the elimination of urea by the kidney, and thus indirectly stimulate the liver. On the same principle, the disposal of the bile furnishes us with a means of rousing the hepatic functions. This brings us to consider the action of indirect cholagogues.

That portion of the circulation of the bile which occurs in the intestine is thoroughly under our control. We can sweep the bowels empty of its contents; and with these the bile, which otherwise would have been re-absorbed, is expelled from the body. The portal blood and liver are thus deprived of material in which the biliary salts exist ready made, namely, their own products; and the hepatic cells are driven to fresh secretion. The purgatives which sweep away the old bile, and so lead to the production of new bile, are called indirect cholagogues. Mercurials specially act upon the liver in this way.

(3) We believe that we can modify the metahohc processes in the liver by specific hepatic stimulants and depressants, irrespective of both the supply and the products. Thus, Phosphorus, Antimony, and Arsenic, increase the metabolic activity of the liver, causing a greater production of urea, and the last two a free flow of bile. Bicarbonate of Soda and Dilute Nitrohydrochloric Acid have probably the same effect as regards the glycogen and the bile. Chloride of Ammonium remarkably increases the amount of urea, apparently by its own decomposition, but still probably through the agency of the liver cells. Iron increases the amount of urea. Amyl Nitrite stimulates the glycogenic function. On the other hand, there can be no question that the whole process of hepatic activity may be remarkably reduced by means of Opium, and to a less degree by Quinia and Alcohol.