TITLE

Cholestasis

AUTHOR(S)
Elferink, R. Oude
PUB. DATE
May 2003
SOURCE
Gut;May2003 Supplement 2, Vol. 52, pIi42
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
In contrast with urine formation, bile flow is not dependent on hydrostatic forces, but driven by osmotic pressure of solutes secreted across the apical membrane of hepatocytes and bile duct epithelial cells. This secretory process is mediated by a set of primary active transporters that use ATP hydrolysis to pump solutes against the concentration gradient. The most important solutes in bile are bile salts, lipids, electrolytes, and organic anions. The direct consequence of the osmotic mechanism of bile formation is that impaired function of these pumps leads to impaired bile flow—that is, cholestasis. The function of these pumps is highlighted by a number of inherited cholestatic diseases, which are caused by mutations in these genes. Identification of the molecular defect in these diseases was not only important for diagnostic reasons but also emphasized that impaired transporter function has pathological consequences. Indeed, it is now becoming clear that impaired or downregulated transporter function is also involved in the pathogenesis of acquired cholestatic syndromes.
ACCESSION #
10074564

 

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