1. Iron deficient and megaloblastic anemias Atanas Stanchev MD University Hospital”Alexandrovska” Clinic of Hematology

2. Anemia

3. Red cells development

4. Normal red cell Size 7µм MCV 82-98fl MCH 27-32pg MCHC 31 0 -34 0 g/l

5. Anemia is a symptom of disease that requires investigation to determine the underlying aetiology . Anemia is strictly defined as a decrease in red blood cell (RBC) mass . I n practice, anemia is usually discovered and quantified by measurement of the RBC count, hemoglobin (Hb) concentration, and hematocrit (Hct)

6. Normal value 40-75  mol/l 40-75  mol/l TIBC 20 – 180  g/l 30 – 180  g/l Ferritin 10.7 - 23  mol/l 12.5 – 26.5  mol/l Iron 34 – 46% 40 – 54% Hct 4.2 – 5.4 T/l 4.6 – 6.6 T/l Er. 1 20-1 6 0 g/l 140-180 g/l Hb Women Men Parameter

8. Iron deficiency anemia

10. Dietary iron enters the enterocyte after being reduced to the ferrous state by duodenal cytochrome b (Dcytb) and being transported by the divalent metal transporter (DMT1). Hephaestin facilitates iron export by ferroportin. Hepatocytes take up either free or transferrin-bound iron and release it back into the circulation via the action of ferroportin. Ferroportin also releases iron from macrophages. Ferroportin-mediated release of iron is inhibited by hepcidin.

20. Reticulocytosis on day 3-4 , max. on day 10

23. Megaloblastic anemia

25. The assimilation of cobalamin. On entering the stomach, dietary cobalamin (Cbl) forms a complex with R binding protein. As this protein is digested in the small intestine, cobalamin is transferred to intrinsic factor (IF). This complex passes through the intestine until it reaches specific receptors on the mucosa of the distal ileum. The internalized Cbl is then transferred to transcobalamin II (TC II), which circulates in the plasma until it binds to receptors on cells throughout the body and is internalized.

26. Folate is essential for the de novo synthesis of purines, serving as an intermediate carrier of 1-carbon fragments used in the biosynthesis of these compounds. Its active form is tetrahydrofolate (THF)..

27. COBALAMIN DEFICIENCY I. Inadequate intake: vegetarians (rare) II. Malabsorption A. Defective release of cobalamin from food : ( Gastric achlorhydria ; Partial gastrectomy ; Drugs that block acid secretion ) B. Inadequate production of intrinsic factor (IF) : ( Pernicious anemia ; Total gastrectomy ; Congenital absence or functional abnormality of IF (rare) ) C. Disorders of terminal ileum : ( Tropical sprue ; Nontropical sprue ; Regional enteritis ; Intestinal resection ; Neoplasms and granulomatous disorders (rare) ; Selective cobalamin malabsorption ) D. Competition for cobalamin : ( Fish tapeworm (Diphyllobothrium latum) ; Bacteria: "blind loop" syndrome ; Drugs: p - aminosalicylic acid, colchicine, neomycin ) III. Other A. Nitrous oxide B. Transcobalamin II deficiency (rare)

33. This marrow section demonstrates so-called nuclear-cytoplasmic dissociation; The slow nuclear maturation is related to a decrease in DNA synthesis related to an insufficient supply of reduced folate to synthesize thymidylate. DNA synthesis inhibitors can produce this picture, as can folate and B12 deficiency.

37. Bone marrow aspirate in megaloblastic anaemia showing early, intermediate and late megaloblasts and a giant metamyelocyte [arrow] .