β Scribed by Serge Erlinger
No coin nor oath required. For personal study only.
Ursodeoxycholic acid, when given to rats in relatively high doses, induces greater choleresis than expected from the amount of bile acids secreted into bile. This phenomenon has been designated hypercholeresis (1). In this issue of HEPATOLOGY, Takikawa, Sano and Yamanaka
(2) offer a new explanation for this intriguing property. Before discussing this paper and the proposed explanation for hypercholeresis, it is necessary to review briefly how most bile acids induce choleresis and how some may induce hypercholeresis. Bile acids are known to be a major determinant of bile flow. They are secreted into bile by a series of transport systems in the hepatocyte that enable concentration of bile acids in canalicular bile. The theory generally accepted to explain why bile acids increase choleresis is the osmotic theory: bile acids (and their associated counterions) increase the osmotic pressure in the canalicular lumen; consequently, water and ions diffuse into the lumen along the osmotic gradient generated by bile acids. According to this theory, the flow of water and ions should be proportional to the output of bile acids (and their associated counterions) in bile. The observations confirm this prediction: in most cases, bile flow is linearly related to bile acid secretion into bile (3). The flow of bile formed per unit of bile acid secreted is generally termed apparent choleretic activity.
Three findings are also best explained by the osmotic theory. The first is that bile acids that do not form micelles, such as dehydrocholate (4), or bile acids with high critical micellar concentrations (and, consequently,
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