Intrinsic factor abnormal

The most frequent cause of cobalamin deficiency is insufficient absorption due to a lack of Intrinsic Factor. This condition is more generally known as pernicious anemia and is caused by the occurrence of autoantibodies against parietal cells and Intrinsic Factor, blocking its capacity to bind cobalamin and preventing its absorption. Less frequent causes are abnormal intestinal flora, partial or total gastrectomy, tropical sprue, fish tapeworm infestation, and the congenital Intrinsic Factor abnormality and Intrinsic Factor receptor dysfunction (Imerslund-Grasbeck disease). 

Vitamin B12 is essential to growth, cell reproduction, the manufacture of myelin (which surrounds some nerve fibers), and blood cell manufacture. The intrinsic factor, which is produced by cells in the stomach, is necessary for the absorption of vitamin B12 in the intestine A deficiency of the intrinsic factor results in abnormal formation of erythrocytes because of the body s failure to absorb vitamin B12, a necessary component for blood cell formation. The resulting anemia is a type of megaloblastic anemia called pernicious anemia. 

The main causes for vitamin B12 deficiency are impaired absorption due to a lack of gastric intrinsic factor (e.g. pernicious anemia), ileal abnormalities, or it can be the result of a strictly vegetarian diet. 

Maintenance therapy consists of 100-1000 meg intramuscularly once a month for life. If neurologic abnormalities are present, maintenance therapy injections should be given every 1-2 weeks for 6 months before switching to monthly injections. Oral vitamin B12-intrinsic factor mixtures and liver extracts should not be used to treat vitamin B12 deficiency ... 

Commonly, achlorhydria may not be accompanied by other diseases, but in some cases theie is a connection. F01 example, achloihydiia is an abnormality that sometimes occurs with severe iron deficiency. Histalog-fast achlorhydria, resulting from intrinsic factor deficiency in gastric juice, may be an indication of pernicious anemia. Hyperplastic polyps are often found in association with achlorhydria. 

Vitamin B12 is available in pure form for oral administration or in combination with other vitamins and minerals for oral or parenteral administration. The choice of a preparation always must be made with recognition of the cause of the deficiency. Although oral preparations may be used to supplement deficient diets, they are of relatively little value in the treatment of patients with deficiency of intrinsic factor or ileal disease. Even though small amounts of vitamin B12 may be absorbed by simple diffusion, the oral route of administration cannot be relied upon for effective therapy in the patient with a marked deficiency of vitamin B12 and abnormal hematopoiesis or neurological deficits. Therefore, the preparation of choice for treatment of a vitamin B12-deficiency state is cyanocobal-amin, and it should be administered by intramuscular or deep subcutaneous injection. 

There are three classes of vitamin B12 binding proteins intrinsic factor, which facilitates absorption of the vitamin from the ileum R-proteins, which include TC I and TC III (the function of these proteins is not clear, but they probably act as mobile storage forms) and TC II, which is the transport protein responsible for carrying the vitamin to the tissues. Abnormalities of intrinsic factor or TC II could be expected to have serious consequences for the patient, and in recent years a number of such abnormalities have been reported. 

Deficiencies of vitamin B12 can result from either low dietary levels or, more commonly, from poor absorption of the vitamin due to the failure of gastric parietal cells to produce intrinsic factor (as in pernicious anemia) or to a loss of activity of the receptor needed for intestinal uptake of the vitamin.5 Nonspecific malabsorption syndromes or gastric resection can also cause vitamin B12 deficiency. The vitamin may be administered orally (for dietary deficiencies), or intramuscularly or deep subcutaneously (for pernicious anemia). [Note Folic acid administration alone reverses the hematologic abnormality and thus masks the B12 deficiency, which can then proceed to severe neurologic dysfunction and disease. Therefore, megaloblastic anemia should not be treated with folic acid alone, but rather with a combination of folate and vitamin B12.] Therapy must be continued for the remainder of the life of a patient suffering from pernicious anemia. There are no known adverse effects of this vitamin. 

Severe gastric atrophy due to Helicobacter pylori infection Congenital abnormalities of intrinsic factor... 

Although these have been linked to malabsorption of B12 (e.g., cause abnormal Schilling tests), they have not been associated with megaloblastic anemia or neuropsychiatric diseases. Intrinsic factor is normally secreted in amounts greatly in excess of normal requirements, so that so that a 90% reduction in intrinsic factor secretion may be of little or no consequence. 

If oral absorption is impaired, part 2 of the test is conducted 5 to 7 days later. The second stage of the Schilling test differentiates inadequate secretion of intrinsic factor by the stomach from an abnormality in absorption by the ileum. Radiolabeled vitamin B12 is administered orally with a sufficient amount of intrinsic factor. Results within the normal range indicate that the defect is in the production of intrinsic factor as opposed to other causes of vitamin B12 deficiency such as dietary deficiency or small bowel pathology. Generally, abnormal results for stage 1 followed by a normal result in stage 2 is consistent with pernicious anemia. 

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. ... 

The disorders associated with abnormal gastric secretion rates and the frequency with which the abnormality occurs are listed in Table 4. In the Zollinger-Ellison syndrome (ZES), basal acid secretion rates are 60% of maximal or greater (BAO/PAO O.6). In addition, decreased gastric acid secretion is rarely seen in patients with the som-atostatinoma syndrome, a condition associated with an islet cell tumor that secretes excessive amounts of somatostatin, a hormone that inhibits acid secretion. There are recent reports of decreased gastric acid, pepsin and intrinsic factor outputs as part of a gastric... 

Autoimmune disorders are characterized by the breakdown of various connective tissues (the collagen diseeises), such as lupus erythematosus, polyarteritis nodosa, rheumatoid arthritis, and rheumatic fever. Also, it is suspected that autoimmune reactions may be responsible in part for certain abnormalities associated with (1) diabetes, when there heis been an unexplainable deterioration of the cells of the pancreas that secrete insulin (2) insufficient secretion of adrenal cortical hormones (Addison s diseeise) due to weisting of the glandular tissue (3) lack of stomach acid (achlorhydria) and/or lack of intrinsic factor resulting in pernicious anemia, because antibodies have attacked the cells of the stomach which secrete the deficient substances and (4) ulcerative colitis, when the lesions are much more severe than might be expected under the circumstances. 

In normal persons, from 30 to 70% of the vitamin B-12 is absorbed as outlined above, in comparison with 1 to 3% absorbed by simple diffusion. Pernicious anemia results from a complete failure to absorb the vitamin, a condition caused by gastric abnormality (usually lack of intrinsic factor). Hence, therapeutic doses of 512 given to pernicious anemia patients usually must be administered intramuscularly. 

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