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.
The liver is by far the largest organ in the body, and it is placed in a very peculiar situation. It acts as a porter or doorkeeper to the circulation, all the substances which are absorbed from the intestinal canal having to pass through the portal vein and the capillaries of the liver before they can enter the general circulation.
Since the discovery by Ludwig and Schmidt-Mulheim that peptones are poisonous when injected directly into the circulation, the liver has acquired a new importance. Schiff and Lautenbach indeed had previously made some experiments which they thought showed that a subtle poison existed in the blood even of healthy animals, but was destroyed by the liver. They based this idea on the observation that ligature of the portal vein causes death in animals with very much the same symptoms as when they are bled to death. Ludwig had formerly explained this phenomenon by supposing that the ligature caused the blood to accumulate in the large and dilatable portal radicles and prevented it from getting into the general circulation again. The animal was thus, as Ludwig expressed it, bled to death into its own veins. Schiff and Lautenbach, however, thought the symptoms were due rather to poison than to this mechanical alteration in the circulation, because they found that when the blood of an animal whose portal vein had been ligatured was injected into a frog, it produced death within three hours, whereas blood from a similar animal whose portal vein had not been ligatured produced no effect.
The liver therefore seems to have a most important function in destroying the poisonous properties of peptones, and perhaps other substances produced during digestion, and possibly also of poisonous products of tissue-waste. The peptones are converted by it into sugar and glycogenic substance.1
It has been for a very long time a matter of clinical experience that the administration of mercurial purgatives was frequently followed by the discharge of greenish bilious-looking evacuations and a great improvement in the general condition of the patient. These two results were classed together as cause and effect, and the improvement was considered to be due to the removal of bile. It was then supposed that the bile was formed in the blood and simply excreted by the liver, and, therefore, the bilious-looking stools were ascribed to stimulation of the secreting function of the liver by the mercurials. Hepatic stimulants and cholagogues were therefore considered to be identical. We now know that the bile is formed in the liver and not simply excreted by it from the blood, and that bile formed in the liver may again be absorbed into the blood. Increased functional activity of the liver might thus lead to the presence of a greater instead of a less quantity of bile in the blood. Recent experiments have also shown that one of the most marked cholagogues which we know, viz. calomel, appears rather to diminish than to increase the actual secretion of bile, so that we are now obliged to distinguish between hepatic stimulants and cholagogues. Hepatic stimulants are drugs which increase the functional activity of the liver, and the amount of bile which it forms. Cholagogues are substances which remove bile from the body, possibly by acting rather on the intestines; they do not necessarily increase the secretion of bile, they may only prevent its re-absorption and thus diminish the quantity in the circulation. Hepatic depressants are drugs which lessen the quantity of bile secreted by the liver.
1 Sesgen, Pfliiger's Archir, xxviii. p. 990.
Fig. 142. - Diagram to show the effect of artificial circulation of blood through the liver, under different pressures. The continuous lines indicate the size of the liver, and the arrangement of the apparatus during circulation, under a low pressure. The dotted lines indicate the increased size of the liver, and the arrangement of the apparatus, under a high pressure.
In relation to tissue-waste it is not to be forgotten that the products of the functional activity of one organ are not only poiso.nous to itself, but may be poisonous to other organs. Thus the waste products of muscular activity gradually poison the muscle and prevent its contraction, although as soon as they are washed out with salt solution the muscle recovers its power.
Lactic acid also, which is a product of muscular waste, is poisonous not only to muscle but to some extent to nerves, and lessens the functional activity of the brain and produces sleep. At the same time it is possible that these waste products, poisonous in themselves, may through slight changes be rendered available for nutrition, just as peptones which are themselves poisonous are most important foods.
Besides acting on peptones, the liver seems to have the power of destroying the poisonous properties of some vegetable alkaloids. For example, 1/20th of a drop of nicotine given to a frog does not produce death, but 1/40th is sufficient, when the liver has been previously removed. Coniine, cobra poison and hyoscyamine, all exert much less poisonous action after they pass through the liver, before they reach the general circulation, than they do when injected directly into the blood. Curare, prussic acid, and atropine, on the other hand, do not have their action modified.1
The result of these experiments may be partly explained on the supposition that a good deal of the poison has been excreted along with the bile, and has thus been prevented from reaching the general circulation. But it is probable that in addition to the function of excreting poisons, the liver has also got the power of destroying poisons, and, it may be, the power of removing poisons from the circulation by merely storing them for a time.