ii EXTEENAL DIGESTIVE SECEETIONS 139 



into bile, or of exciting the secretory metabolism of the hepatic 

 cells, are continuously circulating in the blood that courses through 

 the liver, independent of the digestive products absorbed. 



Evidently these bile-forming and eliminating substances must 

 be katabolic products, both of the cells circulating in the blood and 

 of the fixed tissue-cells. This is proved by the fact that transfusion 

 of blood (particularly when heterogeneous) conspicuously increases 

 the production of bile (Landois). The so-called cholagogues of the 

 pharmacologists are ineffective, save in so far as they destroy the 

 cells of the blood and tissues, the waste products being then 

 elaborated by the liver (Noel Paton, 1886). If dogs with fistula 

 of the gall-bladder are made to ingest the products of nitrogenous 

 consumption, e.g. extractives of meat and uric acid (provided this 

 be rendered soluble and absorbable in the form of potassic urate), 

 there will be a constant augmentation of the bile secretion, with 

 increase of urea in the urine. Ingestion of urea, on the contrary, 

 even in very large doses, does not excite biliary secretion. When 

 it reaches the liver, the urea is entirely taken up by the central 

 veins of the lobules, and excreted by the kidneys. This fact, 

 established by Barbera (1898), proves the continuity of the bile 

 secretion, showing that the extractives and the uric acid which are 

 never absent from the blood of animals, either under ordinary 

 conditions or in fasting, excite metabolism in the hepatic cells, by 

 which they are transformed into urea. Urea, on the contrary, has 

 no action on the liver-cells, because it is the end-product of the 

 oxidation of nitrogenous substances, and is excreted unchanged by 

 the kidneys. 



Barbara's later work (1902) also confirms this theory. Instead 

 of administering the various substances by the mouth or rectum, 

 he injected them subcutaneously in dogs, and studied their action 

 on the bile secretion. Injections of distilled water, of solutions of 

 glucose (up to 10 per cent), of medium doses of sterilised olive oil, 

 and of 5 to V per cent solutions of somatose had no effect on the 

 elimination of bile. On the other hand, he observed increase of 

 the secretion on injection of more concentrated solutions (glucose 

 20 per cent and more, somatose 10 per cent and more), or of large 

 doses of non-sterilised olive oil. But since these last injections 

 simultaneously induce local phenomena of irritation at the point 

 of injection, accompanied by increased elimination of urea and 

 slight rises of temperature, Barbera came to the conclusion that 

 the increase of bile secretion depends not on any direct action of 

 these substances on the hepatic cells, but, indirectly, upon the 

 increased destruction of proteins, the cleavage products of which 

 excite augmentation in the biliary secretion of the liver. 



Another fact worth noting is that the secretion normally 

 poured by the liver into the gall-bladder is not all newly-formed 

 bile : a considerable part of it is only bile reabsorbed from the 



