2. Megaloblastic anaemia (MA) is associated with an abnormal appearance of the bone marrow erythroblasts in which nuclear development is delayed. There is a defect in DNA synthesis caused by deficiency of vitamin B12 (B12, cobalamin) or folate. Hematological indices: Нb ↓↓↓, ret ↓, colour index > 1.05, МСН > 32 pg, MCV > 100 fl, leuc. ↓, neutr. ↓, PLT ↓.

3. В12 metaolism Incomes with food (of animal origin: milk, meat, eggs). In the stomach compounds with intrinsic factor (IF) Absorption – in ileum (at the moment less than 2 mkg, during a day – about 6-9 mkg) In blood compounds with transcobalamines (I,II) Daily requirement is 2-7 mkg Normal mixed diet gives 3-30 mkg of vit В 12 daily Vit. В12 stock is about 2-5 mg, mostly in the liver After absorption of vit. B12 is stopped, storage in the liver can be used for 3-5 years.

4. Folates metabolism Are found in meat, liver, plant products, yeast, milk. Culinary processing destroys the folates. Normal diet supplies 200-400 mkg of folates in respect that daily requirement is 50-100 mkg. Total quantity of folates in the organism is about 10 mg. Storage can be used during 4-5 months

5. Pathogenesis Vitamin B12 and folate are essential coenzymes for the synthesis of nucleotides and therefore of DNA in all the cells, especially in erythroid cells and epithelial cells of GIT and skin. B12 is needed for myelin synthesis as well.

6. Megaloblastic hemopoiesis Proliferation and differentiation of hematopoietic elements disorder Ineffective erythropoiesis Granulocytes and megacariocytes maturation disorder. macrocytic anaemia granulocytopenia thrombocytopenia

7. Aetiology В12 deficiencyFolate deficiency IF secretion disorder Malabsoption in the small intestine Increased demands Malnutrition Transport disorder

8. Clinics 1. Anaemia symptoms 2. GIT lesion 3. Neurologic sympptoms (is absent in folate deficiency!)

9. Diagnosics Normochromic/hyperchromic macrocitic anaemia Leucopenia, relative lymphocytosis Hypersegmentated neutrophils ESR increases in severe anaemia (to 18-20 mm/h) Moderate haemilysis – RBS lifespan shortening (indirect haemoglobin) Megaloblastic type of haemopoiesis in the BM punctate Serum vitamin В12, serum folate norms: Vitamin В 12: 180 – 900 pg/ml Folates: 3 - 17 ng/ml.

10. Pernicious anaemia Autoimmune mechanisms (AB to parietal cells, to IF or to the complex IF-VitВ12) Pathognomonic sign is chronic gastritis with histamine-resistant ahlorhydria Shilling test

11. Is used to evaluate vitamin B12 marked with 57 Со absorption in the small intestine. Patient is given 0,5-2,0 mkg of radioactive vitamin В 12 orally, and then, in 2 hours 1000 мкг of non- radioactive vitamin B12 in given intramuscularly to sate transcobalamin. Since the moment radioactive vitamin B12 is given, daily urine is being collected. Healthy people excrete ≥ 7% of given radioactivity, and people with broken absorption of vitamin В 12 – less than 5% (in pernitious anaemia this index is less than 2%). In insufficiet production of IF its adding to the vitamin B12 marked with 57 Со, at least, 5 times increases radioactivity of the daily urine. Opposite, radioactive vitamin B12 excretion doesn’t change significantly if absorption of vitamin B12 disorder is not connected with IF deficiency.

12. Treatment Nutritive megaloblastic anaemia: diet enriched with folates, folic acid 1-2 mg daily, and vitamins С, В 1, В 6, В 2, РР and others, as folate deficiency is often combined with other vitamins deficiency i/m injections of vitamin B12, 1000 mkg daily during 2 weeks, and then – every week until remission is reached After 1 st injection of vitamin B12 in 24-72 hours megaloblastic hemopoiesis becomes normoblastic To the 5-6 th day red cells count rises because of reticulocytes going to the circulation (reticulocytic crisis). Pernitious anaemia is treated during the lifespan (500 mkg of vitamin B12 1-2 times a month i/m, or vitB12+IF complex: 30 mkg of vitВ 12 and 50 mg of IF per os once a week.