Megaloblastic Anemia & Macrocytic Anemias PDF

‫بسم هللا الرحمن الرحيم‬ Megaloblastic anaemia & other macrocytic anaemias  In macrocytic anaemia the red cells are abnormally large (MCV > 95 fl). Causes are subdivided into: 1-megaloblastic due to deficiency of vitamin B12 &/or folic acid and 2- n...

‫بسم هللا الرحمن الرحيم‬ Megaloblastic anaemia & other macrocytic anaemias  In macrocytic anaemia the red cells are abnormally large (MCV > 95 fl). Causes are subdivided into: 1-megaloblastic due to deficiency of vitamin B12 &/or folic acid and 2- non-megaloblastic,  Megaloblastic anaemia Characterized by: 1- presence of macrocytic RBCs in the peripheral blood. (high MCV)  2- Hypersegmented neutrophils in the peripheral blood -  3- Megaloblastic erythropoiesis in the bone marrow.  In megaloblastic anaemia erythroblasts in the bone marrow are known as the megaloblasts & they show a characteristic abnormality.  maturation of the nucleus is delayed relative to that of the cytoplasm. the delayed maturation of the nucleus is due to defective DNA synthesis. this is usually caused by deficiency of vitamin B12 &/or folate  Vitamin B12 Source: food of animal origin. Minimal daily requirement: 1-2 µg. Stored in the liver – 2-3 mg sufficient for 2-4 years  Vitamin B12 Absorption: Site: terminal ileum mechanism: with intrinsic factor from the stomach (parietal cells)  Vitamin B12 deficiency The deficiency takes at least 2 years to develop (i.e. the time needed for the body stores to deplete).  Causes of Vitamin B12 deficiency 1- Nutritional deficiency : Especially in vegans  2- Malabsorption: * gastric causes * intestinal causes Intestinal causes of B12 deficiency: * Ileal resection * Congenital malabsorption *Fish tape worm (Diphylobothrium latum) Gastric causes of B12 deficiency: * 1- Pernicious anaemia (severe deficiency) *2- Congenital lack or abnormality of intrinsic factor *3- Total or partial gasterectomy  Pernicious anaemia It is an autoimmune disease in which there is:. atrophic gastritis → Loss of parietal cells in the stomach → Failure of production of intrinsic factor Leading to malabsorption of vit B12  Pernicious anaemia is due to parietal cells or intrinsic factor autoantibodies  Pernicious anaemia is more common in females than males. Common in individuals with blood group A  Folic acid: source: green vegetables minimal daily requirement: 100-150 µg  stores: liver, 10-12 mg, sufficient for 4 months. absorption: Site: duodenum &jejunum Mechanism: conversion to tetrahydrofolate  Causes of folic acid deficiency: 1- nutritional deficiency 2- increased demand,excessive utilisation: *Physiological &* pathological  Physiological: pregnancy, lactation, prematurity. Pathological: haemolytic anaemias, malignancy, Inflammatory (exfoliative dermatitis)  3- malabsorption, excessive jejunum resection 4- drugs: anticonvulsant drugs. 5- mixed: liver disease, alcoholism. Clinical features of megaloblastic anaemia General features: Pallor, fatigability, palpitations, breathlessness,Headache  Specific features 1-Glossitis: with a beefy painful red tongue GLOSSITIS Beefy-red &painful tongue  2- Angular stomatitis 3- Progressive neuropathy with severe vit B12 deficiency only (Neurological complication) ANGULAR STOMATITIS 4- sterility in both sexes with severe vit B12 or folate deficiency.  5- Folate or B12 deficiency in the mother predisposes to neural tube defect (anencephaly, spina bifida or encephalocele) spina bifida encephalocele encephalocele anencephaly  Haematological findings Peripheral blood: 1- oval Macrocytes, 2- Hypersegmented neutrophils with 6 or more nuclear lobes. 2-Bone marrow : * Is hypercellular. * Most characteristic finding is delayed nuclear maturation compared to cytoplasmic maturation in the erythroblasts (megaloblasts)  Megaloblasts are large & show failure of nuclear maturation.  Investigations Complete blood count (CBC): pancytopenia Peripheral blood smear: oval macrocytes & hypersegmented neutrophils.  Low serum B12 Low serum & red cell folate. Intrinsic factor antibodies ( in pernicious anaemia)  Treatment: Oral folic acid: in folic acid deficiency Vit B12: hydroxy cobalamin intramuscular injection Other causes of red cell macrocytosis: 1- liver disease 2- pregnancy 3- neonates 4- haemolysis 5- myxoedema