Sequential changes in biliary lipids and gallbladder ion transport during gallstone formation

Area of Science:

• Gastroenterology
• Biliary Physiology
• Molecular Biology

Background:

• Gallstone (GS) formation is linked to altered gallbladder (GB) ion transport and increased biliary lipids and calcium (Ca2+).
• The precise longitudinal relationship between ion transport and biliary lipid changes during GS development remains undefined.

Purpose of the Study:

• To correlate gallbladder (GB) sodium (Na+) and chloride (Cl-) fluxes with biliary lipid composition throughout gallstone (GS) formation.
• To define the sequential changes in GB ion transport during the development of gallstones.

Main Methods:

• Prairie dogs were fed standard or cholesterol-enriched diets for 4 to 21 days.
• Bile was analyzed for lipids and Ca2+; animals were staged as Pre-Crystal, Crystal, or GS.
• Gallbladders were mounted in Ussing chambers to measure electrophysiologic parameters and unidirectional Na+ and Cl- fluxes.

Main Results:

• Short-circuit current and potential difference decreased significantly in the GS stage.
• Net Na+ absorption increased in the Pre-Crystal stage but decreased in the GS stage.
• Increased serosa-to-mucosa flux of Na+ and Cl- characterized the Crystal stage; biliary lipids and Ca2+ correlated positively with ion fluxes.

Conclusions:

• Gallbladder epithelial ion transport changes sequentially during gallstone formation.
• The Pre-Crystal stage shows increased Na+ absorption, while the Crystal stage exhibits prosecretory stimuli on Na+ and Cl- fluxes.
• Elevated GB bile Ca2+ and total bile acids may drive these ion transport changes in later stages.