Anemia, megaloblastic pernicious

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. 

B,2 Cobalamin Coenzyme in transfer of one-carbon fragments and metabolism of folic acid Pernicious anemia = megaloblastic anemia with degeneration of the spinal cord... 

Normal blood levels of vitamin B12 are 2 x 1(T10 M or a little more, but in vegetarians the level may drop to less than one-half this value. A deficiency of folic acid can also cause megaloblastic anemia, and a large excess of folic acid can, to some extent, reverse the anemia of pernicious anemia and mask the disease. 

Which one of the following will reverse symptoms of megaloblastic anemia in pernicious anemia but has minimal impact on the neurologic dysfunction ... 

Pernicious anemia megaloblastic anemia due to lack of intrin-sic factor and B12 malabsorption... 

A. Iron and Vitamin Deficiency Anemias Microcytic hypochromic anemia, caused by iron deficiency, is the most common type of anemia. Megaloblastic anemias are caused by a deficiency of vitamin B, or folic acid, cofactors required for the normal maturation of red blood cells. Pernicious anemia, the most common type of vitamin Bj, deficiency anemia, is caused by a defect in the synthesis of intrinsic factor, a protein required for efficient absorption of dietary vitamin B 2, or by surgical removal of that part of the stomach that secretes intrinsic factor. 

The water-soluble vitamins comprise the B complex and vitamin C and function as enzyme cofactors. Fofic acid acts as a carrier of one-carbon units. Deficiency of a single vitamin of the B complex is rare, since poor diets are most often associated with multiple deficiency states. Nevertheless, specific syndromes are characteristic of deficiencies of individual vitamins, eg, beriberi (thiamin) cheilosis, glossitis, seborrhea (riboflavin) pellagra (niacin) peripheral neuritis (pyridoxine) megaloblastic anemia, methyhnalonic aciduria, and pernicious anemia (vitamin Bjj) and megaloblastic anemia (folic acid). Vitamin C deficiency leads to scurvy. 

Pernicious anemia arises when vitamin B,2 deficiency blocks the metabohsm of folic acid, leading to functional folate deficiency. This impairs erythropoiesis, causing immature precursors of erythrocytes to be released into the circulation (megaloblastic anemia). The commonest cause of pernicious anemia is failure of the absorption of vitamin B,2 rather than dietary deficiency. This can be due to failure of intrinsic factor secretion caused by autoimmune disease of parietal cells or to generation of anti-intrinsic factor antibodies. 

Cya n ocobalamin (Bir) Homocysteine methyltransferase Methylmalonyi CoA mutase Methionine, SAM Odd-carbon fatty acids, Val, Met, He, Thr MCC pernicious anemia. Also in aging, especially with poor nutrition, bacterial overgrowth of terminal ileum, resection of the terminal ileum secondary to Crohn disease, chronic pancreatitis, and, rarely, vegans, or infection with D. latum Megaloblastic (macrocytic) anemia Progressive peripheral neuropathy. ... 

A frequent cause of vitamin B12 deficiency is atrophic gastritis leading to a lack of intrinsic factor. Besides megaloblastic anemia, damage to mucosal linings and degeneration of myelin sheaths with neurological sequelae will occur (pernicious anemia). 

Treatment of pernicious anemia and other megaloblastic anemias where vitamin B-12 is deficient (not effective). 

Pernicious anemia and other megaloblastic anemias secondary to lack of vitamin Bi2. 

Anemias Leucovorin is improper therapy for pernicious anemia and other megaloblastic anemias secondary to the lack of vitamin B- 2-... 

Severe cyanocobalamin (vitamin B12) deficiency results in pernicious anemia that is characterized by megaloblastic anemia and neuropathies. The symptoms of this deficiency can be masked by high intake of folate. Vitamin B12 is recycled by an effective enterohep-atic circulation and thus has a very long half-hfe. Absorption of vitamin B12 from the gastrointestinal tract requires the presence of gastric intrinsic factor. This factor binds to the vitamin, forming a complex that... 

C. The only effective treatment of pernicious anemia is supplementation of vitamin B12.It is important to determine whether megaloblastic anemia is from a deficiency of folic acid or vitamin B12. Treatment of vitamin Bi2-deficient anemia with folic acid may result in neurological damage if vitamin Bi2 is not adequately supplemented. 

Contraindications Pernicious anemia, other megaloblastic anemias secondary to vitamin Bi2 deficiency... 

Cyanocobalamin A cofactor required for essential enzymatic reactions that form tetrahydrofolate, convert homocysteine to methionine, and metabolize l-methylmalonyl-CoA Adequate supplies are required for amino acid and fatty acid metabolism, and DNA synthesis Treatment of vitamin B12 deficiency, which manifests as megaloblastic anemia and is the basis of pernicious anemia Parenteral vitamin B12 is required for pernicious anemia and other malabsorption syndromes Toxicity No toxicity associated with excess vitamin B12... 

Pernicious anemia Dementia Spinal degeneration Megaloblastic anemia Neuropsychiatric symptoms None Pernicious anemia is treated with IM or high-dose oral vitamin B12... 

Vitamin B12 (cobalamin) has as its active forms, methylcobalamin and deoxyadenosyl cobalamin. It serves as a cofactor for the conversion of homocysteine to methionine, and methylmalonyl CoA to succinyl CoA. A deficiency of cobalamin results in pernicious (megaloblastic) anemia, dementia, and spinal degeneration. The anemia is treated with IM or high oral doses of vitamin B12. There is no known toxicity for this vitamin. 

Dietary deticiencies of folic acid are most frequently associated wilh anemias imacroeylic, megaloblastic, and pernicious), glossitis, diarrhea, gastrointestinal lesions, intestinal malabsorption, and sprue. 

Examination of the bone marrow, although important, will only confirm that the hemopoiesis is megaloblastic. A deficiency of folic acid will also cause a megaloblastic anemia and it is not possible to identify the cause on the basis of morphology. A serum assay of both vitamins will usually indicate which is responsible. If the patient is vitamin B12 deficient, the next step is to carry out a vitamin B12 absorption test to confirm that the deficiency is due to a lack of intrinsic factor. Preferably this should not be done until the patient s vitamin B12 and hemoglobin levels have returned to normal, since the gastric and intestinal cells are also affected by a lack of vitamin B12 aborption may be less than optimal if it is attempted too early. Patients with pernicious anemia also have a histamine-fast achlorhydria and gastric atrophy. The disease appears to have an autoimmune basis and antibodies to intrinsic factor can be demonstrated in the serum of more than half of affected patients. 

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... 

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. 

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