728 PHYSIOLOGY OF DIGESTION AND SECRETION. 



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. On the 

 physiological and pharmacological side efforts have been made to 

 discover what substances stimulate especially the formation of bile. 

 Such substances are designated as cholagogues. The therapeutical 

 agents capable 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 increase 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 cholagogues 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. Lastly, there is evidence that the secretin, whose action 

 upon the pancreatic secretion has been described, exerts a similar 

 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.* 

 A similar effect may be obtained by injecting secretin directly into 

 the blood. Since during a meal the stomach normally ejects acid 

 chyme into the duodenum, the importance of this secretin reaction 

 in adapting the secretion of bile to the period of digestion is evident. 

 The Ejection of Bile into the Duodenum Function of the 

 Gall-bladder. Although the bile is formed more or less continu- 

 ously, it enters the duodenum periodically during the time of digestion. 

 The secretion during the intervening periods is prevented from enter- 

 ing the duodenum apparently by the fact that the opening of the 

 common bile-duct is closed by a sphincter. The secretion, therefore, 

 backs up into the gall-bladder. According to Bruns,f no bile appears 



* See Falloise, quoted in Maly's " Jahres-bericht der Thier-chemie, " 33, 

 611, 1904. f" Archives des sciences biologiques, " 7,87, 1899. 



