Pernicious anemia intrinsic factor absence

VITAMIN S12. Fhtients with pernicious anemia are treated with vitamin B12 by tiie parenteral route (IM) weekly stabilized. The parenteral route is used because tiie vitamin is ineffective orally due to the absence of tiie intrinsic factor in tiie stomach, which is necessary for utilization of vitamin B12. After stabilization, maintenance (usually monthly) injections are necessary for life... 

The most likely reason for cobalamin deficiency is pernicious anemia (failure to absorb vitamin B 2 in the absence of intrinsic factor from parietal cells). Vitamin Bjj absorption also decreases with aging and in individuals with chronic pancreatitis. Less common reasons for Bjj deficiency include a long-term completely vegetarian diet (plants don t contain vitamin Bjj) and infection with Diphyllobothrium latum, a parasite found in raw fish. Excess vitamin B,2 is stored in the body, so deficiencies develop slowly. 

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. 

This vitamin is not synthesized in animals, but rather it results from the bacterial or fungal fermentation in the rumen, after which it is absorbed and concentrated during metabolism. Among the known vitamins, this exclusive microbial synthesis is of great interest. One of the major results of vitamin Bn deficiency is pernicious anemia. This disease, however, usually does not result from a dietary deficiency of the vitamin, but rather by an absence of a glycoprotein ( gastric intrinsic factor ) in the gastric juices that facilitates absorption of the vitamin in the intestine. Control of the diseases hence is either by injection of Bn or by oral administration of the intrinsic factor, with or without the vitamin injection. 

Patients with severe atrophic gastritis may have impaired absorption of vitamin B12 and a reduced serum level of the vitamin, but this is not accompanied by either megaloblastic anemia or neuropathy. Parietal-cell antibodies have been found in 33% of patients with gastritis, none of these patients having pernicious anemia (12, V4). Intrinsic factor antibodies were not found, and this was not surprising since it is rare to find antibodies to intrinsic factor in the absence of pernicious anemia. Patients with superficial gastritis usually have normal vitamin B12 absorption and normal serum levels of the vitamin. 

Simons and Grasbeck (S9), using immunoelectrophoresis, did not detect line 7 in pernicious anemia gastric juice. Since line 7, according to the authors, corresponds to the native intrinsic factor-related B12 binder, the absence of this line in pernicious anemia may have significance for the diagnosis of this disease. The rapid vitamin B12 binder was tentatively identified as line 4, whereas the slow (native, intrinsic factor-related) Bi2 binder was localized in the area corresponding to line 7. 

FIGURE 53-8 The absorption and distribution of vitamin Deficiency of vitamin can result from a congenital or acquired defect in any one of the following (1) inadequate dietary supply (2) inadequate secretion of intrinsic factor (classical pernicious anemia) (3) ileal disease (4) congenital absence of transcobalamin II (Tell) or (5) rapid depletion of hepatic stores by interference with reabsorption of vitamin excreted in bile. The utility of measurements of the concentration of vitamin B 2 tn plasma to estimate supply available to tissues can be compromised by liver disease and (6) the appearance of abnormal amounts of transcobalamins I and III (Tcl and III) in plasma. Finally, the formation of methylcobalamin requires (7) normal transport into cells and an adequate supply of folic acid as CH H PteGlu. ... 

Arts. Vitamin 8,2 deficiency, resulting in pernicious anemia, is ordinarily caused by the absence of intrinsic factor, a glycoprotein synthesized in the stomach. Vitamin 8,2 is transported across the intestinal cell membrane as a complex with intrinsic factor. Therefore in individuals who cannot synthesize this protein, the vitamin must be administered by injection directly into the bloodstream. 

V.B12 is also known as antipemicious anemia factor. Pernicious anemia is characterized by a severely reduced production of red blood cells, deficient gastric secretion and disturbances of the nervous system. It is not usually caused by dietary deficiency of V.B]2, but by the absence of intrirrsic factor, which is required for V.B[2 absorption. Intrinsic factor is a neuraminic acid-containing glycoprotein, normally present in the gastric mucosa, which forms a pepsin-resistant complex with V.B,2, and enables V.B,2 absorption in the lower part of the intestinal traet. 

These recommended daily allowances provide for a margin of safety to cover variance in individual needs, absorption, and body stores. However, in using this table as a nutritional guide, the following facts should be noted (1) exact daily human requirements of vitamin B-12 cannot be given because it is synthesized by intestinal flora (2) in the absence of intrinsic factor (e.g., pernicious anemia), the vitamin is not absorbed and (3) it is assumed that at least 50% of the vitamin B-12 in food is absorbed. 

Cobalamin is the anti-pernicious anemia factor. Minutest amounts (a few micrograms) cure pernicious anemia in man. The disease is characterized by a drastic decrease of the erythrocyte count (due to a disturbance in the maturation of red blood cells). Pernicious anemia does not arise from a dietary deficiency, but rather is caused by a defect in the absorption of the vitamin. Cobalamin (designated the extrinsic factor, in this connection) can be taken up by the human organism only in the presence of the intrinsic factor, a mucoprotein. The latter is formed in the gastric mucosa its absence causes pernicious anemia. 

---