Enterohepatic circulation

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Enterohepatic Circulation.

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Enterohepatic circulation refers to the circulation of bile from the liver, where it is produced, to the small intestine, where it aids in digestion of fats and other substances, back to the liver.

Liver hepatocytes metabolize cholesterol to cholic acid and chenodeoxycholic acid. These lipid soluble bile acids are conjugated mainly to glycine or taurine molecules to form water soluble primary conjugated bile acids. These bile acids travel to the gall bladder during the interdigestive phase for storage and to the second part of the duodenum via the common bile duct during digestion. 95% of the bile acids which are delivered to the duodenum will be recycled by the enterohepatic circulation.

At 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. If bile does escape, jaundice may be observed.

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.

Enterohepatic circulation also means that some molecules which would not otherwise be very toxic can become extremely hepatotoxic as they reach unexpectedly high hepatic concentrations. Drugs may remain in the enterohepatic circulation for a prolonged period of time as a result of this recycling process.

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