Biliary canaliculus

Figure 2.2 Secretion of bile acids and biliary components. Bile acids (BA) cross the hepatocyte bound to 3a-hydroxysteroid dehydrogenase and are exported into the canaliculus by the bile-salt export protein (BSEP). Phosphatidylcholine (PC) from the inner leaflet of the apical membrane is flipped to the outer layer and interacts with bile acids secreted by BSEP. BA, PC, together with cholesterol from the membrane form mixed micelles that are not toxic to epithelial membranes of the biliary tree. Aquaporins (AQP) secrete water into bile.

The transfer of conjugated bilirubin in the hepatocyte across the bile canaliculus deposits the conjugated bilirubin along with other hepatic secretions into the biliary system for transport to the small intestine. This transport process is catalyzed by one or more members... 

Bile acids, which have been taken up by the liver, are transported across the hepatocyte and secreted into the bile canaliculus. Newly synthesized bile acids, in a small amount just sufftcient to balance the fraction lost by fecal excretion, join recycled bile acids for biliary secretion. Intracellular bile acid transport may be mediated by carrier proteins (B24, S42). The detailed mechanism of biliary secretion of bile acids and other organic anions into the bile canaliculus is not yet clear (B24). Possible mechanisms include vectorial vesicular transport, fticilitated diflusion, or an energy-requiring carrier-mediated transport process (B24). 

It has been suggested that the limiting factor in the maximal transfer of BSP from the cell to the bile canaliculus is the concentration of the dye in the canaliculus at the excretory membrane (03). Since bile salts are probably secreted at the same anatomical site as BSP (A14, C15) and produce an increased excretion of water at that site, the local concentration of BSP can be maintained only by an increase in the rate of BSP excretion. Choleretics, e.g., secretin, which initiate a secretion of water at some other site, do not effect the excretion of BSP, and biliary concentrations of the dye are reduced (03, Wll). 

Recent physical-chemical observations on native mammalian systems reveal that the proposed mixed micellar mechanism of lipid solubilization and transport in both bile and in upper small intestinal contents is incomplete [1,260-263]. Bile is predominantly a mixed micellar solution but, particularly when supersaturated with Ch, also contains small liquid-crystalline vesicles which, as suggested from model systems [239], are another vehicle for Ch and L transport. In dog bile which is markedly unsaturated with Ch [258], these vesicles exist in dilute concentrations and may be markers of the detergent properties of BS on the cells lining the biliary tree and/or related to the mode of bile formation at the level of the canaliculus. In human hepatic bile, which is generally dilute and markedly supersaturated with Ch, these vesicles may be the predominant form of Ch and L solubilization and transport [261]. If hepatic bile is extremely dilute, it is theoretically possible that no BS-L-Ch micelles may be present [268] all of the lipid content may be aggregated... 

If it is of interest that biliary storage of BSP in patients with the Dubin-Johnson syndrome fell within the normal range (52,53), allowing the possibility that the mechanism for the extraction of the dye from plasma by the liver is unimpaired. Thus one may speculate that the site of competition between bile salts and anionic dyes is at the hepatic uptake (or storage) stage and that subsequent secretion from the cell into the canaliculus of the two substances may proceed by separate mechanisms. 

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