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. 2003 May;52(Suppl 2):ii42–ii48. doi: 10.1136/gut.52.suppl_2.ii42

Cholestasis

R Elferink
PMCID: PMC1867745  PMID: 12651881

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 emphasised 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.

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Figure 1 .

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Transporters involved in canalicular bile formation. In the left canalicular membrane the ABC transporters are indicated, of which the function has been established. In the right canalicular membrane the heterodimer of ABCG5 and ABCG8 has been drawn, but this is speculative because the presence of these two half transporters in the canalicular membrane has not been demonstrated yet. It has also not yet been proved that phytosterols are transported by this transporter pair.

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