Enterohepatic Circulation

Bile salts secreted into the intestine are efficiently reabsorbed (>95%) and reused. The liver actively secretes bile salts via the bile salt export pump.

In the intestine, they are reabsorbed in the terminal ileum via the apical sodium (Na⁺)–bile salt cotransporter and returned to the blood via a separate transport system. [Note: Lithocholic acid is only absorbed.]  They are efficiently taken up from blood by the hepatocytes via an isoform of the cotransporter and reused. [Note: Albumin binds bile salts and transports them through the blood as was seen with FA.]

The continuous process of secretion of bile salts into the bile, their passage through the duodenum where some are de-conjugated then de-hydroxylated to secondary bile salts, their uptake in the ileum, and their subsequent return to the liver as a mixture of primary and secondary forms is termed the enterohepatic circulation (Fig. 1). Between 15 and 30 g of bile salts are secreted from the liver into the duodenum each day, yet only ~0.5 g (<3%) is lost daily in the feces. Approximately 0.5 g/day is synthesized from cholesterol in the liver to replace the amount lost.

Bile acid sequestrants,  such as cholestyramine, bind bile salts in the gut and prevent their reabsorption, thereby promoting their excretion. They are used in the treatment of hypercholesterolemia because the removal of bile salts relieves the inhibition on bile acid synthesis in the liver, thereby diverting additional cholesterol into that pathway. [Note: Dietary fiber also binds bile salts and increases their excretion .

Figure 1:  Enterohepatic circulation of bile salts. [Note: Ionized bile acids are called bile salts.]