TY - JOUR
T1 - The biliary HCO(3)(-) umbrella
T2 - a unifying hypothesis on pathogenetic and therapeutic aspects of fibrosing cholangiopathies.
AU - Beuers, Ulrich
AU - Hohenester, Simon
AU - de Buy Wenniger, Lucas J.Maillette
AU - Kremer, Andreas E.
AU - Jansen, Peter L.M.
AU - Elferink, Ronald P.J.Oude
PY - 2010/10
Y1 - 2010/10
N2 - This review focuses on the hypothesis that biliary HCO(3)(-) 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(3)(-) 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(3)(-) exchange and HCO(3)(-) secretion, and alkaline phosphatase-mediated ATP breakdown may guarantee a stable biliary HCO(3)(-) umbrella under physiological conditions. Genetic and acquired functional defects leading to destabilization of the biliary HCO(3)(-) umbrella may contribute to development and progression of various forms of fibrosing/sclerosing cholangitis.
AB - This review focuses on the hypothesis that biliary HCO(3)(-) 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(3)(-) 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(3)(-) exchange and HCO(3)(-) secretion, and alkaline phosphatase-mediated ATP breakdown may guarantee a stable biliary HCO(3)(-) umbrella under physiological conditions. Genetic and acquired functional defects leading to destabilization of the biliary HCO(3)(-) umbrella may contribute to development and progression of various forms of fibrosing/sclerosing cholangitis.
UR - http://www.scopus.com/inward/record.url?scp=77957940106&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/hep.23810
DO - https://doi.org/10.1002/hep.23810
M3 - Review article
C2 - 20721884
SN - 0270-9139
VL - 52
SP - 1489
EP - 1496
JO - Hepatology (Baltimore, Md.)
JF - Hepatology (Baltimore, Md.)
IS - 4
ER -