Effect of biliary pressure versus high bile acid flux on the permeability of hepatocellular tight junction.

Creation of a shunt between the common bile duct and vena cava, choledocho-caval shunt (CCS), causes biliary retention without obstruction. This in turn induces a marked choleresis (up to three times the normal bile flow) and increases bile acid output, both of which reach a plateau by 6 hours and remain elevated thereafter. In contrast, bile duct obstruction produces high biliary pressure and stoppage of bile flow and bile acid output. To compare the effect of biliary pressure and bile acid flux on permeability of the hepatocellular tight junction, we examined lanthanum permeation through tight junctions and bile to plasma concentration ratios of 3H-sucrose in these two models. In addition, we examined the effect of biliary pressure further by adjusting biliary pressure to 15 cm of H2O in modified CCS animals. At 6 hours after establishing these experimental models in male Sprague-Dawley rats, we infused lanthanum chloride (5 mM) in physiologic saline through the aorta (120 mm Hg) for 3 minutes, followed by perfusion fixation of the liver. Transmission electron microscopy on 144 bile canaliculi in each group (three rats each) revealed penetration of lanthanum in descending order of pressure rather than bile acid output: bile duct obstruction (50.7%), modified CCS (19.4%), CCS (13.2%), and control (5.6%). Bile to plasma concentration ratios of 3H-sucrose measured at 0, 2, and 6 hours in CCS and modified CCS animals revealed a marked increase of bile to plasma ratios only in the modified CCS group. These data lead us to conclude that biliary pressure is the significant determinant of biliary permeability and that bile acid output is important only insofar as the resultant choleresis elevates pressure.