This section is from the book "A Text-Book Of Pharmacology, Therapeutics And Materia Medica", by T. Lauder Brunton. Also available from Amazon: A text-book of pharmacology, therapeutics and materia medica.
In making experiments, similar to those of Rutherford and Vignal, Schiff observed that the secretion of bile was very much greater for a short time immediately after the bile-duct was tied, than it was later on; and on further investigation he found that this was due to the fact that the liver has a double function; it not only forms new bile, but re-excretes the old bile which has been re-absorbed from the intestine. A certain quantity of bile is lost in the faeces, but a considerable portion of it seems to be utilised again and again; being formed by the liver, poured out into the intestine, reabsorbed and again excreted. This circulation of bile between the intestine and the liver has been called by Lussana the entero-hepatic circulation (Fig. 143). It has been shown that the bile which is absorbed from the duodenum does not merely act as a stimulus to the liver to cause a greater formation of new bile, but is actually re-excreted, by injecting ox-bile, which gives Pettenkofer's reaction, into the duodenum of a guinea-pig, and finding that shortly afterwards the bile which issued from the gall-duct gave this reaction while the bile normally secreted by the guinea-pig does not.
Fig. 143. - Entero-Hepatic Circulation.
Not only is bile re-excreted in this manner by the liver, but other substances also, such as medicines and poisons, are likewise excreted. The absorption and re-excretion take place with great rapidity, for Laffter, in some experiments made under Heidenhain's direction, found that rhubarb injected into the duodenum appeared in the bile in less than five minutes. Substances injected into the blood were also excreted by the bile with great rapidity, so that sulphindigotate of sodium, introduced directly into the circulation in some experiments, began to colour the bile blue one minute after its injection. Other substances are also absorbed from the intestine and excreted by the liver and passed round in the entero-hepatic circulation, just like the bile. Curare is one of these, and to this probably is due in a great measure the absence of fatal effect from its introduction into the stomach. Iron also circulates with the bile, and it is probable that the beneficial effect of large doses may be due in part to the action of the iron upon the liver. The objection has been raised to the employment of large doses that they are useless, inasmuch as the whole of the iron which is taken into the mouth is again expelled in the faeces, but there can be no doubt that clinically large doses of iron are sometimes beneficial. Copper and manganese also appear in the bile, and it is probable that lead and all the heavy metals pass chiefly out of the body by this channel. For the action of the liver on alkaloids see p. 401.
It has been suggested by Lussana that the malarial poison also circulates in the entero-hepatic circulation.
From the fact that bile is re-absorbed from the intestine, it is obvious that an hepatic stimulant which simply increases the secretion of the bile by the liver, will not of itself act as a cholagogue and remove the bile from the body. In order to do this, this action must be combined with increased peristaltic action of the bowels, which will hurry the bile out and prevent its re-absorption. If, in addition to increased peristalsis, we have increased secretion from the intestinal mucous membrane, so as to wash out the intestine, we shall get the bile still more effectually removed from the body. The necessity for such a combination has indeed been long ago shown by clinical experience, and the advantages of following a mercurial pill by a saline purgative in order to clear it away have long been recognised. Some hepatic stimulants increase also the peristaltic movements and secretions from the intestine - for example, those substances which have been already enumerated as cholagogue purgatives.
Colchicum in large doses.
In most cases, however, it is advisable to combine hepatic and intestinal stimulants in order to ensure a more complete cholagogue effect. Thus calomel as employed in Rutherford's experiments has no stimulant action on the liver, but stimulates the intestinal glands; corrosive sublimate, on the contrary, stimulates the liver powerfully but has a very feeble stimulant action on the intestine; a combination of the two stimulates both the liver and the intestinal glands. When used in medicine, calomel is recognised to be a powerful cholagogue, one of the most powerful indeed that we possess, and it is by no means impossible that a small portion of it may be converted into corrosive sublimate in the intestine, so that we thus get from the calomel, when given alone, the combined effects of both the mercurial preparations just mentioned. It is more probable, however, that the cholagogue action of calomel is due to its having a peculiar stimulant action on the duodenum and ileum, so as to hurry the bile along the intestine and prevent its re-absorption. The reason for supposing that this is the case rather than that part of it is converted into corrosive sublimate and stimulates the liver, is that when given to dogs with a permanent fistula it does not increase the flow of bile, which it would probably do if any corrosive sublimate were formed. Another is that after the administration of calomel, leucin and tyrosin, which are products of pancreatic digestion, are found in the stools, and it seems not improbable that their appearance under such circumstances is due to their having been hurried along the intestine from the duodenum to the anus, and evacuated without time being allowed for their absorption or decomposition in the intestine.
Adjuncts to Cholagogues. - The pressure under which bile is secreted is very low, so that a very slight obstruction to its flow through the common bile-duct is sufficient to cause its accumulation in the gall-bladder and gall-ducts, and thus to lead to its re-absorption. This is readily observed in cases of catarrh, either of the duodenum or of the gall-ducts. In such cases the use of ipecacuanha is indicated. This drug has been found clinically to be of great service, and it probably acts by lessening the tenacity of the mucus in the gall-duct, and thus tends to remove the obstruction in front, while at the same time it increases the pressure behind, by stimulating the hepatic secretion. The movements of the diaphragm have a powerful action in aiding the expulsion of bile from the liver; they do this to a certain extent in ordinary respiration, but their effect is much greater in forced inspiration. Exercise therefore tends to expel bile from the liver, and prevent its accumulation in the biliary capillaries, but a little brisk exercise as in riding, rowing, climbing, tennis, etc, will have in a few minutes a more beneficial action than a lazy constitutional walk of a couple of hours.
The secretion of bile is not only increased, but the pressure under which it is secreted is raised by sipping fluids. This is, in all probability, due to nervous influence, for it has been shown by Kronecker that taking a liquid in numerous small sips will for the time completely abolish the inhibitory action of the vagus on the heart. It is probably in consequence of this fact, that Carlsbad water, when taken in numerous sips for an hour or more, as at Carlsbad itself, is so exceedingly efficacious in hepatic diseases, while sodium sulphate, which is the main constituent of the water, was found by Rutherford to have only a very slight action as a stimulant to the liver.
Uses of Hepatic Stimulants and Cholagogues.- The pressure under which the bile is secreted is very small, but the blood-pressure also in the portal vein is very low. In consequence of this a very slight increase in the tension of the bile within the gall-ducts, or diminution of the pressure of blood in the vein, causes the bile to be absorbed. It is then carried by the circulation to various parts of the body and disturbs their functions. It lessens the power of the heart and appears to diminish the activity of the brain, so that persons suffering from biliousness and presenting a slight icteric tinge of the conjunctiva, are apt to feel irritable, stupid, and out of sorts generally. Cholagogues are useful by removing bile from the body, and thus relieving the symptoms above mentioned. It is probable, however, that they also in some way improve the portal circulation, and thus lessen congestion of the stomach and intestines, as in Beaumont's experiments on Alexis St. Martin (p. 369).