Folic acid Megaloblast

Folic acid Megaloblastic anemia, diarrhea, glossitis Serum folate Decreased with increased cellular/tissue turnover (pregnancy, malignancy, hemolytic anemia) masks neurologic complications of vitamin B12 deficiency decreases risks of neural tube defects... 

May et al. (1950a,b, 1951) originally considered that ascorbic acid was necessary for the conversion of pteroylglutamic acid to citrovorum factor. In monkeys fed on diets deficient both in ascorbic acid and folic acid, megaloblastic anemia developed. This could be relieved by ascorbic acid, by folic acid in large doses, or by small doses of citrovorum factor. Later May et al. (1953) reported that ascorbic acid was not required for the conversion of folic acid to citrovorum factor. The severe deficiency of folic acid compounds occurring in scorbutic monkeys was probably due to nonspecific factors operating in scurvy. 

It is recommended that women of childbearing age take 400 pg/d synthetic folic acid as a supplement in order to reduce the risk of neural tube defects of the embryo when they later become pregnant (periconcep-tional folic acid supplementation) [2]. When supplementing folic acid, it should be considered that this vitamin can mask the simultaneous presence of vitamin B12 deficiency. The typical symptom of vitamin B12 deficiency, megaloblastic (= macrocytic) anemia, will be reduced by high doses of folic acid, yet the nervous system will - in the long run - be irreversibly damaged (= funicular myelitis) when vitamin B12 is not provided as well. 

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. 

Folic acid Coenzyme in transfer of one-carbon fragments Megaloblastic 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... 

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. 

Folic acid deficiency is also related to megaloblastic anemia. Tetrahydrobiopterin is a co-factor for phenylalanine, tyrosine, and tryptophane hydroxilases — enzymes... 

Macrocytic anemias Megaloblastic anemias Vitamin B12 deficiency Folic acid deficiency anemia Microcytic hypochromic anemias Iron-deficiency anemia Genetic anomaly Sickle cell anemia Thalassemia... 

A modification of the above serum folic assay method was recently described (W4). The investigators confirmed the validity of this technique as a practical means of differentiating patients with folic acid from vitamin B12 megaloblastic anemias. Another modification of this method was also described (C4). These investigators reduced the over-all sensitivity by high serum dilutions and thus made the assay, as they used it, valueless as a diagnostic tool. 

Medoxomil, molecular formula and structure, 5 153t Mefluidide, 73 43t, 54 Megaloblastic anemia, folic acid and, 25 802... 

In view of the reported growing importance ascribed to folic acid deficiency in the prevention of various disease conditions, such as neural tube defects, megaloblastic anemia, colon cancer, and colorectal cancer, a dissolution requirement is specified for folic acid when it is present in multivitamin-mineral combination products. Currently, the dissolution standard required in the official articles of dietary supplements (including vitamin-mineral combination products) places folic acid outside the index vitamin hierarchy. Therefore, a mandatory dissolution test for folic acid is required that is independent of and in addition to the mandatory index vitamin test for multivitamin preparations containing folic acid. 

Enzymes dependent on folic acid as coenzyme include participants in the synthesis of thymine, an essential component of DNA, and methionine, a common amino acid in proteins, among other important metabolites. A deficiency of folic acid results in the disease megaloblastic anemia. 

Folate, the anion of folic acid, is made up of three different components—a pteridine derivative, 4-aminobenzoate, and one or more glutamate residues. After reduction to tetrahydrofolate (THF), folate serves as a coenzyme in the Q metabolism (see p. 418). Folate deficiency is relatively common, and leads to disturbances in nucleotide biosynthesis and thus cell proliferation. As the precursors for blood cells divide particularly rapidly, disturbances of the blood picture can occur, with increased amounts of abnormal precursors for megalocytes megaloblastic anemia). Later, general damage ensues as phospholipid... 

Megaloblastic anem/a.- Treatment of megaloblastic anemias due to a deficiency of folic acid as seen in tropical or nontropical sprue, anemias of nutritional origin, pregnancy, infancy, or childhood. 

Pharmacology Exogenous folate is required for nucleoprotein synthesis and maintenance of normal erythropoiesis. Folic acid stimulates production of red and white blood cells and platelets in certain megaloblastic anemias. 

Folic acid appears in the plasma approximately 15 to 30 minutes after an oral dose peak levels are generally reached within 1 hour. After IV administration, the drug is rapidly cleared from the plasma. Folic acid is metabolized in the liver. Normal serum levels of total folate have been reported to be 5 to 15 ng/mL normal CSF levels are approximately 16 to 21 ng/mL. In general, folate serum levels less than 5 ng/mL indicate folate deficiency, and levels less than 2 ng/mL usually result in megaloblastic anemia. A majority of the metabolic products appeared in the urine after 6 hours excretion was generally complete within 24 hours. 

Parenteral Treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible. 

Megaloblastic anemia due to folic acid deficiency No more than 1 mg leucovorin/day. There is no evidence that doses greater than 1 mg/day have greater efficacy than 1 mg doses. 

Hematologic Hematopoietic complications, some fatal, include thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, and pancytopenia. Macrocytosis and megaloblastic anemia usually respond to folic acid therapy. Eosinophilia monocytosis leukocytosis simple anemia hemolytic anemia aplastic anemia ecchymosis. 

Anemia Administration has been associated in a few cases with vitamin B-12 or folic acid deficiency, megaloblastic anemia, and sideroblastic anemia. If evidence of anemia develops, institute appropriate studies and therapy. 

Patients with folic acid deficiency may have diarrhea and nausea, but the principal symptoms are weakness and easy fatigability due to megaloblastic anemia arising from impaired cell division in the bone marrow. 

The answer is D. Several vitamin deficiencies can cause anemia due to reduced DNA synthesis in the erythropoietic cells of the bone marrow, especially folic acid and vitamin Bj2 (cobalamin), which are particularly prevalent among elderly patients due to poor diet and reduced absorption. In addition, deficiencies of either folic acid or vitamin Bj2 could produce the megaloblastic anemia seen in this patient. However, the absence of neurologic symptoms, a hallmark of vitamin Bj2 deficiency, makes that diagnosis less likely than folic acid deficiency. 

Folic acid is used for the treatment of folate deficiency. Oral folic acid is usually the therapy of choice. For megaloblastic anemia doses of 5 mg daily for 4 months should be effective. Folinic acid is available in a parenteral formulation which may be indicated when oral therapy is not feasible and for rescue treatments following certain anti-cancer regimens. 

Without a firm diagnosis folic acid should not be given to all patients with megaloblastic anemia as irreversible neurological damage from vitamin B12... 

Folic acid deficiency symptoms include megaloblastic anemia, glossitis, diarrhea, and weight loss. The requirement for this vitamin increases during pregnancy and lactation. 

Megaloblastic anemia is characterized by the appearance of large cells in the bone marrow and blood due to defective maturation of hematopoietic cells. Folic acid or vitamin B12 deficiency will result in this type of anemia. Malabsorption, impaired use, chronic infections, and drugs can lead to folic acid or vitamin B12 deficiency. 

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. 

CBC serum folate concentrations <0.005 mcg/ml indicate folic acid deficiency and concentrations <0.002 mcg/ml usually result in megaloblastic anemia... 

Folic acid antagonist overdose PO 2-15 mg/day for 3 days or 5 mg every 3 days. Megaloblastic anemia secondary to folate deficiency IM 1 mg/day Colon cancer IV 200 mg/m followed by 370 mg/m fluorouracil daily for 5 days. Repeat course at 4-wk intervals for 2 courses then 4-5 wk intervals or 20 mg/m followed by 425 mg/m fluorouracil daily for 5 days. Repeat course at 4-wk intervals for 2 courses then 4-5 wk intervals. 

The serious toxic effect is hyperkalemia. Triamterene produces relatively few other side effects which includes nausea, vomiting, dizziness etc. Megaloblastic anaemia has been reported in patients with alcoholic cirrhosis, which is probably due to inhibition of dihydrofolate reductase in patients with reduced folic acid intake. 

Deficiency symptoms The characteristic feature of folic acid deficiency is megaloblastic anaemia. Deficiency also leads to glossitis, enteritis, diarrhoea, general debility, weight loss and sterility. 

It is indicated in folic acid deficiency states e.g. megaloblastic anaemia, tropical... 

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