[PDF][PDF] The biliary HCO3− umbrella: A unifying hypothesis on pathogenetic and therapeutic aspects of fibrosing cholangiopathies
U Beuers, S Hohenester, LJM de Buy Wenniger… - …, 2010 - Wiley Online Library
Hepatology, 2010•Wiley Online Library
This review focuses on the hypothesis that biliary HCO secretion in humans serves to
maintain an alkaline pH near the apical surface of hepatocytes and cholangiocytes to
prevent the uncontrolled membrane permeation of protonated glycine‐conjugated bile
acids. Functional impairment of this biliary HCO umbrella or its regulation may lead to
enhanced vulnerability of cholangiocytes and periportal hepatocytes toward the attack of
apolar hydrophobic bile acids. An intact interplay of hepatocellular and cholangiocellular …
maintain an alkaline pH near the apical surface of hepatocytes and cholangiocytes to
prevent the uncontrolled membrane permeation of protonated glycine‐conjugated bile
acids. Functional impairment of this biliary HCO umbrella or its regulation may lead to
enhanced vulnerability of cholangiocytes and periportal hepatocytes toward the attack of
apolar hydrophobic bile acids. An intact interplay of hepatocellular and cholangiocellular …
Abstract
This review focuses on the hypothesis that biliary HCO secretion in humans serves to maintain an alkaline pH near the apical surface of hepatocytes and cholangiocytes to prevent the uncontrolled membrane permeation of protonated glycine‐conjugated bile acids. Functional impairment of this biliary HCO umbrella or its regulation may lead to enhanced vulnerability of cholangiocytes and periportal hepatocytes toward the attack of apolar hydrophobic bile acids. An intact interplay of hepatocellular and cholangiocellular adenosine triphosphate (ATP) secretion, ATP/P2Y‐ and bile salt/TGR5‐mediated Cl−/ HCO exchange and HCO secretion, and alkaline phosphatase–mediated ATP breakdown may guarantee a stable biliary HCO umbrella under physiological conditions. Genetic and acquired functional defects leading to destabilization of the biliary HCO umbrella may contribute to development and progression of various forms of fibrosing/sclerosing cholangitis. (HEPATOLOGY 2010)
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