Document Detail

Chronic fibrosing cholangiopathies: a consequence of a defective HCO₃⁻ "umbrella"?
MedLine Citation:
PMID:  21809484     Owner:  NLM     Status:  In-Process    
The pathogenesis of chronic cholangiopathies, in particular primary biliary cirrhosis and primary sclerosing cholangitis, is still obscure. A stimulating hypothesis is proposed by Beuers et al. They reason that, since cholangiocytes are exposed to high concentrations of hydrophobic bile salts that are toxic at μM concentrations, these cells had to develop protective mechanisms. Apart from micelle formation, the authors argue that biliary HCO₃⁻ secretion serves to maintain an alkaline pH near the apical surface of cholangiocytes by forming a HCO₃⁻ "umbrella". In this alkaline environment, glycine conjugated bile salts (which are predominant in man), with a pKa of ~4, remain deprotonated and are unable to permeate the apical membrane and cause cell damage. Functional impairment of biliary HCO₃⁻ secretion leads to enhanced vulnerability of cholangiocytes toward the attack of hydrophobic bile salts, causing cell damage and cholangitis. Such an impairment could be due to genetic factors, like mutations of the anion exchanger 2 (a variant of the Cl⁻/HCO₃⁻ exchanger) in primary biliary cirrhosis or of TGR5 (a bile salt receptor implicated in the regulation of HCO₃⁻ secretion) in primary sclerosing cholangitis. This stimulating hypothesis is amenable to experimental testing and has potential pathophysiological and therapeutic implications.
Serge Erlinger
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinics and research in hepatology and gastroenterology     Volume:  35     ISSN:  2210-741X     ISO Abbreviation:  Clin Res Hepatol Gastroenterol     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-08-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101553659     Medline TA:  Clin Res Hepatol Gastroenterol     Country:  France    
Other Details:
Languages:  eng     Pagination:  85-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Masson SAS. All rights reserved.
University of Paris 7, Paris, France.
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