Gastric secretion intrinsic factor

Persons who have a congenital decrease in the number of gastric cells secreting intrinsic factor... 

Bi2 are only about 2 meg, it would take about 5 years for all of the stored vitamin B12 to be exhausted and for megaloblastic anemia to develop if Bi2 absorption were stopped. Vitamin B12 in physiologic amounts is absorbed only after it complexes with intrinsic factor, a glycoprotein secreted by the parietal cells of the gastric mucosa. Intrinsic factor combines with the vitamin Bi2 that is liberated from dietary sources in the stomach and duodenum, and the intrinsic factor-vitamin Bi2 complex is subsequently absorbed in the distal ileum by a highly selective receptor-mediated transport system. Vitamin Bi2 deficiency in humans most often results from malabsorption of vitamin B12 due either to lack of intrinsic factor or to loss or malfunction of the specific absorptive mechanism in the distal ileum. Nutritional deficiency is rare but may be seen in strict vegetarians after many years without meat, eggs, or dairy products. 

Pernicious anemia results from defective secretion of intrinsic factor by the gastric mucosal cells. Patients with pernicious anemia have gastric atrophy and fail to secrete intrinsic factor (as well as hydrochloric acid). The Schilling test shows diminished absorption of radioactively labeled vitamin B12, which is corrected when intrinsic factor is administered with radioactive B12, since the vitamin can then be normally absorbed. 

Parietal cells also secrete intrinsic factor, which is necessary for the absorption of vitamin B12. Vitamin B12 is a cofactor of enzymes which synthesise tetrahydrofolic acid, which in turn is needed for the synthesis of DNA components. An impairment of DNA synthesis will affect rapidly dividing cell populations, among them the haematopoietic cells of the bone marrow, which may result in pernicious anaemia. This condition may result from a destruction of the gastric mucosa by, for example, autoimmune gastritis or the resection of large parts of the lower ileum, which is the main site of vitamin B12 absorption, or of the stomach. 

Vitamin B12 is special in as far as its absorption depends on the availability of several secretory proteins, the most important being the so-called intrinsic factor (IF). IF is produced by the parietal cells of the fundic mucosa in man and is secreted simultaneously with HC1. In the small intestine, vitamin B12 (extrinsic factor) binds to the alkali-stable gastric glycoprotein IF. The molecules form a complex that resists intestinal proteolysis. In the ileum, the IF-vitamin B 12-complex attaches to specific mucosal receptors of the microvilli as soon as the chymus reaches a neutral pH. Then either cobalamin alone or the complex as a whole enters the mucosal cell. 

Megaloblastic anemias Deficiency of vitamin 6,2 Decreased absorption of 6,2, often due to a deficiency of intrinsic factor, normally secreted by gastric parietal cells... 

Castle then showed (1929) that beef muscle was as effective as liver in preventing pernicious anemia, provided it was administered with normal gastric juice. He therefore concluded two factors were involved—an extrinsic one which was a component in liver or muscle and an intrinsic factor which was secreted by the stomach. Major efforts were therefore directed at identifying the extrinsic factor in liver or other meats. 

Cobalamine can only be resorbed in the small intestine when the gastric mucosa secretes what is known as intrinsic factor—a glycoprotein that binds cobalamine (the extrinsic factor) and thereby protects it from degradation. In the blood, the vitamin is bound to a special protein known as trans-cobalamin. The liver is able to store vitamin Bi2 in amounts suf cient to last for several months. Vitamin B12 deficiency is usually due to an absence of intrinsic factor and the resulting resorption disturbance. This leads to a disturbance in blood formation known as pernicious anemia. 

Gastric motility Secretion of pepsin Secretion of gastric acid Secretion of intrinsic factor... 

Histamine has long been recognized as a powerful stimulant of gastric acid secretion and, to a lesser extent, of gastric pepsin and intrinsic factor production. The effect is caused by activation of H2 receptors on gastric parietal cells and is associated with increased adenylyl... 

This condition has often been referred to in the past as juvenile pernicious anemia but it appears to be a quite separate entity. Confusion probably arose because there is a deficiency of intrinsic factor resulting in vitamin B12 malabsorption in both conditions. However, it differs from the disease in adults in that free acid is present in the gastric secretion (A8,L3,M5), the gastric mucosa is usually normal, and antibodies to intrinsic factor are not a feature. Megaloblastic anemia usually develops during the first 2 years of life but this depends on the amount of residual intrinsic factor available, and... 

Water-soluble vitamins are absorbed by special transport proteins, some require active transport, others facilitated diffusion in order to cross the gastric lumen. Vitamin B12 cannot be absorbed by itself it has to be bound to intrinsic factor which is secreted into the lumen of the stomach by the parietal cells. Intrinsic factor binds to vitamin B12 to form a complex that is subsequently absorbed in the ileum. 

Patients with B12 deficiency often have problems absorbing the vitamin. The gastric mucosa secretes an intrinsic factor which binds B12 to form a complex, allowing absorption in the ileum. When secretion of intrinsic factor is diminished, B12 absorption is reduced, for example in gastric cancers, inflammatory states, trauma or surgery. 

Q1 The stomach acts as a temporary reservoir for food and as a mixing chamber, allowing small amounts of gastric contents (chyme) to enter the duodenum at intervals. The acid environment and mechanical activity in the stomach starts the breakdown of food items and the acidity of the stomach eliminates many infectious organisms present in ingested material. Finally, an important function is the production and secretion of intrinsic factor, a compound that is necessary for effective absorption of vitamin Bi2 from the diet. 

Failure of intrinsic factor secretion is commonly a result of autoimmune disease 90% of patients with pernicious anemia have complement-fixing antibodies in the cytosol of the gastric parietal cells. Similar autoantibodies are found in 30% of the relatives of pernicious anemia patients, suggesting that there is a genetic basis for the condition. 

For patients who secrete antiintrinsic factor antibodies in the saliva or gastric juice, oral intrinsic factor will be of no benefit. 

Atrophic gastritis will cause decreased secretion of gastric acid before there is any impairment of intrinsic factor secretion. This means that the absorption of crystalline vitamin B12, as used in the Schilling test, is normal but the absorption of protein-bound vitamin B12 from foods will be impaired (Section 10.7.1), and the Schilling test will give a false-negative result. 

The human Bu-binder intrinsic factor is a glycoprotein of ca. 44kDa, with a high binding constant (in 1 1 complexes) for vitamin B12 (1) and other cobalamins. The intrinsic factor is secreted by cells of the gastric mucosa and specifically binds cobalamins and carries them to the ileum. There the ileum receptor protein accepts the corrinoid from the intrinsic factor complex and transports it further across the intestinal epithelial absorptive cell. The cobalamins then appear to be bound to transcobalamin II and transported in the blood in this way to membrane-bound transcobalamin/corrin receptor proteins of the specific cells. ... 

Because plants are devoid of vitamin B12, the supply of humans and animals is ultimately of bacterial origin (although humans can obtain vitamin B12 via animal products such as meat, milk, and milk products). A glycoprotein designated intrinsic factor that is secreted by the human gastric mucosa enables the take-up of the vitamin, which is then converted into coenzyme B12 by a series of enzyme reactions that occur in the human host (7). 

FUNCTION Activates secretion of gastric acid, pepsin, and intrinsic factor (the vagus nerve stimulates gastrin release). 

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