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Megaloblastic anemia Due to B12 and folate deficiencies. Folic acid deficiency Sources and requirements: •Known as folate or petroyl glutamic acid. •Water soluble. •Present in a variety of foods (green leafy vegetables, fruits and liver and kidney). •Heat labile vitamin. •Dietary intake for adults 30µg/kg per day. Structure: Folic acid •Made of three components. •Folic acid derived from diet is not biologically active. •Once absorbed through the duodenum it hydrolyzed, reduced and methylated to form MTHF. •Other form THF (biologically active). Pterdine Amino benzoic acid Gultamic acid (Poly Glutamic Acid) Absorption and metabolism Intestine Diet Poly glutamic acid Poly glutamate Folate reductase Glu Mono glutamate CH3THF Methyl Tetrahydrfolate DNA Synthesis cTHF Glu THF Homocysteine Methionine CH3THF CH3THF Tissue cell Circulation Causes of folic acid deficiency 1. The main causes is decrease dietary intake: • Old age, • Alcoholism • Chronic diseases. 2. Mal absorption: • Tropical sprue. • Gluten-sensitive enteropathy. 3. Increase requirements: • Pregnancy. • Infancy. • Malignancy. 4. Drugs: • Methotrexate, oral contraceptives. Laboratory diagnosis of megaloblastic anemia • CBC Low hemoglobin level and elevated MCV. • PB morphology Macrocytosis, macroovalocytes and hyper segmented neutrophils. • Chemical testing Serum folic acid Low (RC FA) • BM Hyper cellular BM. Megaloblastic picture (large cells with increased RNA per DNA unit. Nuclear chromatin appears loose and less mature than nuclear chromatin of normal red cells. Megakaryocytes may be hypersegmented. Giant bands and hypersegmented polymorphonuclear neutrophils are common. Differential Lab Diagnosis of Megaloblastic anemia High MCV >98 fl Check smear for macrocytes and hyper segmented neutrophils Yes Serum B12 Serum folate Red cell folate NO All normal Alcoholism Liver diease ?Hematologic diease Decreased level of B12 Decreased red cell folate Anti-IF antibodies Folic acid deficiency Anti-IF antibodies No Yes Schilling test Abnormal corrected with IF Abnormal Not corrected IF Normal Dietary deficiency P.A. Mal absorption