PHYSIOLOGY OF THE LIVER AND SPLEEN. 819 



produce the secretion probably go on at all times, but they are 

 increased when the blood-flow is increased. We may believe, there- 

 fore, that the quantity of the bile secretion varies with the quantity 

 and composition of the blood flowing through the liver, and that 

 the blood contains normally chemical substances which stimulate 

 the liver cells to secrete bile. It is stated on the basis of experi- 

 mental evidence* that when the supply of portal blood is cut off 

 the amount of bile formed is greatly reduced, and that, therefore, 

 it is possible that the substances from which bile is formed or 

 which serve to stimulate the production of bile are furnished chiefly 

 by the portal blood. Substances which stimulate the formation of 

 bile are designated as cholagogues. The therapeutical agents cap- 

 able of giving this action are still a subject of controversy. On 

 the physiological side the following facts are accepted : Any agent 

 that causes an hemolysis of red corpuscles increases the flow of 

 bile, or the same effect is produced if a solution of hemoglobin is 

 injected directly into the blood. This result is in harmony with the 

 views already stated regarding the significance of the bile pigments* 

 as an excretory product of hemoglobin. The cholagogue whose 

 action is most distinct and prolonged is bile itself. When fed 

 or injected directly into the circulation, bile causes an undoubted in- 

 crease in the secretion. This effect is due both to the bile acids and 

 bile pigments. Since the bile acids have a hemolytic effect on red 

 corpuscles, it might at first be assumed that their action as chola- 

 gogues is due indirectly to this circumstance. The action of the 

 bile acids is, however, much more pronounced than that of other 

 hemolytic agents, and it seems certain, therefore, that they exert 

 a specific effect on the liver cells. So also it is stated (Weinberg) 

 that peptones and proteoses have a marked stimulating effect, 

 and since these substances may be brought to the liver in the 

 portal blood, it is possible that they act as stimuli under normal 

 conditions. Lastly, there is evidence that the secretin, whose ac- 

 tion upon the pancreatic secretion has been described, exerts a sim- 

 ilar effect upon the secretion of bile. Statements differ somewhat in 

 regard to the extent of this action, but it seems to be certain that, 

 when acids (0.5 per cent. HC1) are injected into the duodenum or upper 

 part of the jejunum, the secretion of bile is increased; and, since 

 this effect takes place when the nervous connections are severed, the 

 effect, as in the case of the pancreatic secretion, is explained by as- 

 suming that the acid converts prosecretin to secretin, and this 

 latter after absorption into the blood acts upon the liver cells. f 



* Voegtlin and Bernheim, "Journal of Pharmacology and Exp. Therapeu- 

 tics/' 2, 455, 1910. 



t See Falloise, quoted in Maly's "Jahres-bericht der Thier-chemie," 33, 

 611, 1904. 



