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Megaloblastic anemias

Megaloblastic anemias MA are a group of disorders characterized by defective nuclear maturation caused impaired DNA synthesis. This is usually due to vitamin B12 or folate deficiencies. Vitamin B12 Sources and requirements : Produced by micro-organisms and fungi.

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Megaloblastic anemias

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  1. Megaloblastic anemias • MA are a group of disorders characterized by defective nuclear maturation caused impaired DNA synthesis. • This is usually due to vitamin B12 or folate deficiencies. • Vitamin B12 • Sources and requirements: • Produced by micro-organisms and fungi. • Present in foods of animal origin (meat, liver, fish, eggs) • The recommended dietary intake for adult is 2g/day.

  2. Structure: • The vitamin consists of small group of compounds called cobalamin. • Water soluble with MW 1335 daltons. • Transport and metabolism: • Two important proteins involved in the transport of Vit B12: • From diet to ileum (Intrinsic factor [IF]). • From ileum to tissues (Transcbalamins I, II, III [TCII]).

  3. Diet Stomach Transportation path of Vit B12 Bone marrow (DNA synthesis) B12 + IF B12 IF Liver (storage) Ileum B12+IF TCII Other tissues (DNA synthesis) B12 +TCII Circulation

  4. Vit B12 plays important role in two reactions: • Necessary in the synthesis of methionine from homocysteine. • In this reaction both vit B12 and folic acid are involved. • B12 acts as a co-enzyme (methyl cobalamin) for methyltransferase. methionine Methyl B 12 Homocysteine THF Methyl THF • Vit B12 is important in conversion of methylmalonyl CoA to succinyl CoA in Krebs cycle. • In this reaction B12 acts as co-enzyme for methylmalonyl Co A mutase. Adenosyl Cb Ado B12 Methylmalonyl Co A Succinyl Co A

  5. Vitamin B 12 deficiency • Due to other causes • Nutritional (Vegans). • Malabsorption. • Intestinal causes (intestinal stagnant loop syndrome). • Congenital malabsorption with proteinuria. • Fish tapewarm. • Due to intrinsic factor deficiency (Pernicious anemia) • Congenital lack or abnormality of intrinsic factor. • Total or partial gastrectomy. • Adult PA.

  6. Pernicious anemia • A disease characterized By Gastric parietal atrophy leading to decreased secretion of intrinsic factor and other gastric juices.

  7. Clinical manifestations: • Weakness, fatigue, shortness of the breath. • Laboratory diagnosis: • Red cell indices • Low Hb level, elevated MCV (>98fl). • Blood film • shows macro-ovalocytes and hypersegmented neutrophils. • Multinucleate RBCs • Howell-Jolly bodies • Chemical testing • Low levels of serum B12. • In case PA • Antibodies to IF are present in the serum. • Schilling test.

  8. PB Morphology Macro-ovalocytes Hypersegmented neutrophils Bi-nucleated RBCs Howell-Jolly bodies

  9. The Schilling test • Radioactive cobalamin (Cbl*) is taken orally; followed by injection of a saturating dose of non-radioactive cobalamin. • The level of Cbl* is measured in the urine. In pernicious anemia the excreted levels of Cbl* are low. • If intrinsic factor is given with the Cbl* the Cbl* levels will correct in PA, but not in ileal malabsorption.

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