Megaloblastic anemia folate deficiency causing

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. 

Folate deficiency results in a megaloblastic anemia that is microscopically indistinguishable from the anemia caused by vitamin B12 deficiency (see above). However, folate deficiency does not cause the characteristic neurologic syndrome seen in vitamin B12 deficiency. In patients with megaloblastic anemia, folate status is assessed with assays for serum... 

Be aware of how folate deficiency causes megaloblastic anemia. 

Causes of megaloblastic anemia Folate and cobalamin deficiency. Patients with folate deficiency have similar hematologic and GI findings but do not have the neurologic symptoms as with cobalamin deficiency. 

Jean Ann Tonich developed a folate deficiency and is on the verge of devel-j oping a cobalamin (vitamin B12) deficiency as a consequence of prolonged moderately severe malnutrition related to chronic alcoholism. Before folate therapy is started, the physician must ascertain that the megaloblastic anemia is not caused by a pure B12 deficiency or a combined deficiency of folate and B12. 

Megaloblastic anemia A deficiency in serum hemoglobin and red blood cells (erythrocytes) in which the erythrocytes are abnormally large. This type of anemia is caused by folate or vitamin B, deficiency. 

Fohc acid is a precursor of several important enzyme cofactors required for the synthesis of nucleic acids (qv) and the metaboHsm of certain amino acids. Fohc acid deficiency results in an inabiUty to produce deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and certain proteins (qv). Megaloblastic anemia is a common symptom of folate deficiency owing to rapid red blood cell turnover and the high metaboHc requirement of hematopoietic tissue. One of the clinical signs of acute folate deficiency includes a red and painhil tongue. Vitamin B 2 folate share a common metaboHc pathway, the methionine synthase reaction. Therefore a differential diagnosis is required to measure foHc acid deficiency because both foHc acid and vitamin B 2 deficiency cause... 

Vitamin deficiency can cause a megaloblastic anemia of the same type seen in folate deficiency (discussed in Chapter 17). In a patient with megaloblastic anemia, it is important to determine the underlying cause because Bjj defidency, if not corrected, produces a peripheral neuropathy owing to aberrant fatty acid incorporation into the myelin sheets associated with inadequate methylmalonyl CoA mutase activity. Excretion of methylmalonic acid indicates a vitamin Bjj deficiency rather than folate. 

Flypersensitivity to TMP or SMZ megaloblastic anemia caused by folate deficiency ... 

Folic acid deficiency can be caused by drugs. Methotrexate and, to a lesser extent, trimethoprim and pyrimethamine, inhibit dihydrofolate reductase and may result in a deficiency of folate cofactors and ultimately in megaloblastic anemia. Long-term therapy with phenytoin can also cause folate deficiency, but only rarely causes megaloblastic anemia. 

Parenteral administration of folic acid is rarely necessary, since oral folic acid is well absorbed even in patients with malabsorption syndromes. A dose of 1 mg folic acid orally daily is sufficient to reverse megaloblastic anemia, restore normal serum folate levels, and replenish body stores of folates in almost all patients. Therapy should be continued until the underlying cause of the deficiency is removed or corrected. Therapy may be required indefinitely for patients with malabsorption or dietary inadequacy. Folic acid supplementation to prevent folic acid deficiency should be considered in high-risk patients, including pregnant women, patients with alcohol dependence, hemolytic anemia, liver disease, or certain skin diseases, and patients on renal dialysis. 

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. 

A number of methods have been developed to permit assessment of folate and vitamin B12 nutritional status and to differentiate between deficiency of the vitamins as a cause of megaloblastic anemia. Obviously, detection of antibodies to intrinsic factor or gastric parietal cells will confirm autoimmune pernicious anemia rather than nutritional deficiency of either vitamin. 

Vitamin B12 deficiency can also cause megaloblastic anemia. White-centered hemorrhages can occur in the posterior pole, and disc pallor also may be seen. If the anemia is severe, cotton-wool spots may appear. A complete blood count can confirm that megaloblastic anemia exists. Serum folate and vitamin B12 levels should be determined and appropriate therapy (intramuscular injections of hydroxocobalamin) should be instituted at the earliest sign of megaloblastic anemia. 

The major cause of megaloblastic anemia in children is folate deficiency. The following case indicates the importance of including regular supplementation of parenteral nutrition with folate (74). 

Triamterene blocks dihydrofolate reductase and can cause folate deficiency with megaloblastic anemia and pancytopenia, particularly in patients with hepatic cirrhosis, who have reduced clearance of the drug (SED-11, 431). When this has been reported, all patients were taking doses of 150-600 mg/day for ascites and all had hepatic cirrhosis, often due to alcohol abuse (SEDA-17, 269). It is advisable to use spironolactone rather than triamterene in patients with cirrhosis. 

Folate and vitamin B12 deficiencies result in decreased DNA and RNA synthesis, which causes a megaloblastic anemia. Tetrahydrofolate (FH4) is directly involved in providing carbon for thymine (and thus DNA) synthesis and for synthesis of the purines (see Figure 7-20). If vitamin B12, which accepts methyl groups from 5-methyl-FH4, is deficient, 5-methyl-FH4 accumulates. Since this compound cannot be reconverted... 

Hemolysis, if sufficiently severe, produces an LD isoenzyme pattern similar to that in myocardial infarction. Megaloblastic anemias, usually resulting from the deficiency of folate or vitamin cause the erythrocyte precursor cell to break down in the bone marrow (ineffective erythropoiesis), resulting in the release of large quantities of LD-1 and LD-2 isoenzymes. Marked elevations of the total LD activity in serum— up to 50 times the upper reference limit—have been observed in the megaloblastic anemias. These elevations rapidly return to normal after appropriate treatment. 

Several drugs (e.g., sulfasalazine, trimethoprim-sulfamethoxazole, and methotrexate) have been reported to cause a fohc acid deficiency megaloblastic anemia. These drugs either interfere with folate absorption or inhibit the dihydrofolate reductase enzyme necessary for conversion of dihydrofolate to its active tetrahydrofolate form (see Chap. 102, on drug-induced blood dyscrasias). 

B. Megaloblastic anemia is caused by a decrease in the synthesis of deoxythymidylate and the purine bases usually caused by a deficiency in either THF or cobalamin or both. This results in decreased DNA synthesis, which results in abnormally large hematopoietic cells created by perturbed cell division and DNA replication and repair. This patient exhibits signs of chronic alcoholism, which often leads to a folate deficiency. This can occur due to poor dietary intake, decreased absorption of folate due to damage of the intestinal brush border cells and resulting conjugase deficiency, and poor renal resorption of folate. 

Megaloblastic anemia has two most likely causes, deficiency of folate and deficiency of cobalamin. Often treatment of patients with cobalamin deficiency improves in terms of their hematologic features with treatment with folate but not in their neurologic symptoms. What is the most likely explanation for this explanation ... 

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