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 ga llstone (GS) formation. Summary Background Data GS formation is associ ated with altered GB ion transport and increased biliary lipid and Ca2 + concentrations. Nonetheless, the longitudinal relationship between i on transport and biliary lipid changes during GS formation has not bee n defined. Methods Prairie dogs were led standard (n = 18) or 1.2% cho lesterol-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 G S, respectively. GBs were mounted in Ussing chambers, electrophysiolog ic parameters were recorded, and undirectional Na+ and Cl- fluxes meas ured. Results Short-circuit current and potential difference were simi lar during Pre-Crystal and Crystal stages but significantly reduced du ring GS stage compared to controls and Pre-Crystals. Transepithelial r esistance was similar in all groups. Net Na+ absorption was increased during Pre-Crystal but decreased during GS Stage due to increased muco sa-to-serosa and serosa-to-mucosa flux, respectively, Increased serosa -to-mucosa flux of both Na+ and Cl- characterized the Crystal stage. B iliary lipids and Ca2+ increased progressively during various stages o f GS formation and correlated positively with undirectional fluxes of Na+ and Cl-. Conclusion GB epithelial ion transport changes sequential ly 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 ele vated GB bile Ca2+ and total bile acids.