Concept
Enterohepatic circulation refers to the circulation of biliary acids, bilirubin, drugs or other substances from the liver to the bile, followed by entry into the small intestine, absorption by the enterocyte and transport back to the liver. Enterohepatic circulation is an especially important concept in the field of toxicology as many lipophilic xenobiotics undergo this process causing repeated liver damage. Hepatocytes metabolize cholesterol to cholic acid and chenodeoxycholic acid. These lipid-soluble bile acids are conjugated (reversibly attached) mainly to glycine or taurine molecules to form water soluble primary conjugated bile acids, sometimes called "bile salts". These bile acids travel to the gall bladder during the interdigestive phase for storage and to the descending part of the duodenum via the common bile duct through the major duodenal papilla during digestion. 95% of the bile acids which are delivered to the duodenum will be recycled by the enterohepatic circulation. Due to the pH of the small intestine, most of the bile acids are ionized and mostly occur as their sodium salts which are then called “primary conjugated bile salts.” In the lower small intestine and colon, bacteria dehydroxylate some of the primary bile salts to form secondary conjugated bile salts (which are still water-soluble). Along the proximal and distal ileum, these conjugated primary bile salts are reabsorbed actively into hepatic portal circulation. Bacteria deconjugate some of the primary and secondary conjugated bile salts back to lipid-soluble bile acids, which are passively absorbed into hepatic portal circulation. Finally, the conjugated bile acids which remained un-ionized conjugated bile acids are passively absorbed. Venous blood from the ileum goes straight into the portal vein and then into the liver sinusoids. There, hepatocytes extract bile acids very efficiently, and little escapes the healthy liver into systemic circulation. The net effect of enterohepatic recirculation is that each bile salt molecule is reused about 20 times, often multiple times during a single digestive phase.
