Where is intrinsic factor secreted

It is rapidly bound by one of two vitamin B 12 -binding proteins that are present in gastric juice; at acid pH, these binding proteins have a greater affinity for the vitamin than does intrinsic factor. In the small intestine, pancreatic proteases digest the binding proteins, releasing vitamin B 12 which then becomes bound to intrinsic factor.

Finally, there are receptors for intrinsic factor on the ileal mucosa which bind the complex, allowing vitamin B 12 to be absorbed into portal blood. In all mammals, vitamin B 12 is necessary for maturation of erythrocytes, and a deficiency of this vitamin leads to development of anemia.

Since efficient absorption of vitamin B 12 in humans depends on intrinsic factor, diseases which decrease the secretion of intrinsic factor e. In the stomach cobalamin is liberated from its protein binding by peptic digestion and bound to R-proteins.

Hypochlorhydria or achlorhydria, whether medically induced or not, may impair cobalamin uptake. The cobalamin-R-protein complex is split by pancreatic enzymes in the duodenum, where cobalamin is bound to intrinsic factor. Pancreatic insufficiency may lead to cobalamin deficiency. Lack of intrinsic factor is the commonest cause of cobalamin deficiency; very rarely, aberrant forms of intrinsic factor are produced, but the clinical syndrome is similar.

Gram-negative anaerobe bacteria bind the cobalamin-intrinsic factor complex, and bacterial overgrowth of the small intestine diminishes cobalamin resorption. Parasitic infections with fish tape-worm and Giardia lamblia are also associated with cobalamin malabsorption.

The cobalamin-intrinsic factor complex binds to the ileal receptors in the terminal ileum. Cobalamin absorption may be impaired after resection or by diseases affecting more than 50 cm of the terminal ileum, such as Crohn's disease, coeliac disease, tuberculosis, lymphoma or radiation.