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

Objective This study sought to correlate gallbladder (GB) Na+ and Cl-) fluxes with biliary lipid composition during the various stages of gallstone (GS) formation. Summary Background Data GS formation is associated with altered GB ion transport and increased biliary lipid and Ca2+ concentrations. Nonetheless, the longitudinal relationship between ion transport and biliary lipid changes during GS formation has not been defined. Methods Prairie dogs were led standard (n = 18) or 1.2% cholesterol-enriched (n = 30) diets for 4 to 21 days, Hepatic and GB bile were analyzed for lipids and Cage. Animals were designated either Pre-Crystal, Crystal, or GS based on absence or presence of crystals or GS, respectively. GBs were mounted in Ussing chambers, electrophysiologic parameters were recorded, and undirectional Na+ and Cl- fluxes measured. Results Short-circuit current and potential difference were similar during Pre-Crystal and Crystal stages but significantly reduced during GS stage compared to controls and Pre-Crystals. Transepithelial resistance was similar in all groups. Net Na+ absorption was increased during Pre-Crystal but decreased during GS Stage due to increased mucosa-to-serosa and serosa-to-mucosa flux, respectively, Increased serosa-to-mucosa flux of both Na+ and Cl- characterized the Crystal stage. Biliary lipids and Ca2+ increased progressively during various stages of GS formation and correlated positively with undirectional fluxes of Na+ and Cl-. Conclusion GB epithelial ion transport changes sequentially during GS formation? with the early Pre-Crystal stage characterized by increased Na+ absorption, and the later Crystal stage accompanied by prosecretory stimuli on Na+ and Cl- fluxes, which may be due to elevated GB bile Ca2+ and total bile acids.