بسم الله الرحمن الرحیم

1. بسم الله الرحمن الرحیم

2. Аnemia– pathologic state,accompanied by decrease in the level ofhemoglobin and the quantity of erythrocytes per unit of volume of the blood.

3. Erythrocytes - less informative index of anemia than the level of hemoglobin therefore, in the general practice the basic criterion of severity is precisely Hb: Light degree of anemia - Hb 110-90 g / l, The average degree of severity - Hb 90-70 g / l, Severe anemia - Hb below 70 g / liter

4. Laboratory Definition of Anemia • Hgb: • Women: <12.0 • Men: < 13.5 • Hct: • Women: < 36 • Men: <41

5. RBC Life Cycle • In the bone marrow, erythropoietin enhances the growth of differentiation of burst forming units-erythroid (BFU-E) and colony forming units-erythroid (CFU-E) into reticulocytes. • Reticulocyte spends three days maturing in the marrow, and then one day maturing in the peripheral blood. • A mature Red Blood Cell circulates in the peripheral blood for 100 to 120 days. • Under steady state conditions, the rate of RBC production equals the rate of RBC loss. • Erythropoetin role

7. Classification of Anemia • I. Anemias resulting from acute blood loss • II. Anemias resulting from a deficit of erythropoesis 1) At the expense of maturation (mainly microcyte): • violation of absorption and utilization of iron (iron) • violation of transportation of iron (atransferrinemia) • violation of recycling iron (thalassemia, sideroblastic anemia ) • violation of reutilization of iron (anemia of chronic disease);

8. Anemia (continued) 2) At the expense of differentiation (essentially normal): • aplastic anemia (congenital and acquired) 3) At the expense of proliferation (mainly macrocytes) • B12-DEFICIENCY anemia • Folic-DEFICIENCY anemia.

9. Anemia (continued) • Anemias resulting from increased destruction of erythroid series cells - haemolytic: • 1) caused by internal defects of erythrocytes membranopathy, enzimopathy, haemoglobinopathies; • 2) the external (extracllular) effects: • autoimmune, traumatic, etc. • Classification D. Nathan, F. Oski, 2003, (book «Anemias in children», NA Finogenova et al, 2004.):

10. The clinical value of blood

12. Measurements of Anemia • Hemoglobin = grams of hemoglobin per 100 mL of whole blood (g/dL) • Hematocrit= percent of a sample of whole blood occupied by intact red blood cells • RBC = millions of red blood cells per microL of whole blood • MCV = Mean corpuscular volume • If > 100→ Macrocytic anemia • If 80 – 100 → Normocytic anemia • If < 80 → Microcytic anemia • RDW = Red blood cell distribution width • = (Standard deviation of red cell volume ÷ mean cell volume) × 100 • Normal value is 11-15% • If elevated, suggests large variability in sizes of RBCs

13. Anemia due to Decreased Response to Erythropoietin • Iron-Deficiency • Vitamin B12 Deficiency • Folate Deficiency • Anemia of Chronic Disease

15. Iron Deficiency • Can result from: • Pregnancy/lactation • Normal growth • Blood loss • Intravascular hemolysis • Gastric bypass • Malabsorption • Iron is absorbed in proximal small bowel; decreased abosrption in celiac disease, inflammatory bowel disease • May manifest as PICA • Tendency to eat ice, clay, starch, crunchy materials • May have pallor, koilonychia of the nails, beeturia • Peripheral smear shows microcytic, hypochromic red cells with marked anisopoikilocytosis.

16. Iron Deficiency Anemia - koilonychia

17. Iron in the Body

19. Serum Transferrin(Beta-globulin). • Main function - transport of absorbed iron in the depot (liver, spleen), into the medullaryerythroid predecessors and into the reticulocytes. • Basic place of synthesis - liver. • An increase in the content of transferrin with lowering in the level of iron of serum is characteristic for the iron-deficiency state. • A decrease in the level of transferrin can be with the damage of the liver (different genesis) and with the loss of protein (for example, in nephrotic syndrome). • The level of transferrin is increased in the last term of pregnancy.

20. Transferrin LIMITATION • The concentration of TF is subjected to the daily variations • Acute inflammation contributes to lowering the TF level CLINICAL SIGNIFICANCE • Basic clinical index for the differentiation between the iron-deficiency ([TF]↑) and hemolytic anemia ([TF]↓) • More precise index than total iron binding capacity • After the liberation of iron from the complex, TF ion of Fe3+ must be restored into Fe2+

21. Ferritin • water-soluble complex of iron hydroxide with the protein apoferritin. • It is located in cells of the liver, spleen, bone marrow, in the reticulocytes. • Ferritin is the basic protein in human which deposits iron and concentration of ferritin in the serum reflects the reserve of iron in the organism.

22. Iron Deficiency Anemia – Lab Findings • Serum Iron • LOW (< 50 micrograms/dL) • Total Iron Binding Capacity (TIBC) • HIGH ( > 360 micrograms/dL) • Serum Ferritin • LOW (< 20 nanograms/mL) • Can be “falsely”normal in inflammatory states

24. Treatment of Iron Deficiency Anemia • Oral iron salts • Ferrous sulfate – 325 mg(50 mg absorption) • Side effects: constipation, black stools, positive hemmoccult test • Vitamin C can facilitate iron absorption.

25. Treatment of Iron Deficiency Anemia • Diet: meat, liver, yeast, fish • Oral preparations: recovery rate Hb does not differ from parenteral introduction, side effects are less, excessive introduction does not lead to hemosiderosis. - Dosage : 1 hour prior to the meal in the evening time (absorption increase in the second-half of a day)

26. Possibilities : dark colour of stool and transitory dyspeptic disorders (nausea, diarrhea or watery stool) Check analysis of the blood: in 7-10 days – reticulocyte reaction; 4 weeks - increase Hb and Ht - Iron tolerance test(2 tablet-2 h-100 micro/dl During the normalization of the indices of the blood – reduce the dose of preparation

27. in exceptional cases in severe iron deficiency anemia intolerance of oral preparations (after repeated replacement and reduction in the dose) diseases of gastro-intestinal tract syndrome of the disrupted intestinal absorbtion after the extensive resection of the small intestine continuous blood loss Parenteral Introduction of Iron

28. Complications of Parenteral Introduction • Local reactions (pains, phlebitis) • General reactions (anaphylaxis, fever, head and articulate pains, vomiting, rash, bronchospasm). Preparations: Venofer - for the intravenous introduction, Maltofer, Ferrum-Lek - intramuscular

29. Overdose of Iron In the first 6-8 hours - epigastral pains, nausea, vomiting (including with the blood), diarrhea, pallor, sleepiness, acrocyanosis) For 12-24 hours - metabolic acidosis, leukocytosis, there can be spasms, coma, after 2-4 days - necroses of the liver and kidneys. Treatment: emetic means, stomach lavage, the method of milk with the egg white, Deferoksamin, Desferal, symptomatic therapy.

30. Iron Overload Syndrome • Human does not have special mechanism of the excretion of iron! Its excessive introduction leads to hemosiderosis. Clinical manifestations: Gradual increase of the dimensions of the liver, spleen, cardiopathy, suprarenal insufficiency, diabetes mellitus Laboratory signs: • Increase in serum iron (more than 30 mmol/liter), percentage of saturation transferrin by iron it is more than 50%, ferritin of serum it is more than 1000 ng/ml

31. Megaloblastic Anemia • A subclass of macrocytic anemia (under morphologic classification) Or • A subclass of anemias due to defective DNA synthesis (pathogenetic classification)

37. Vit.B12 • Average diet contains 5 – 30g Vit. B12 daily • The amount of Vit. B12 in the body is about 2 – 5 mg. • Most of it is in the liver. • The store is sufficient for 3-6 years in case of impaired absorbtion. • The storage form is mainly adenosylcobalamin.

38. B12 in diet R-Binder Parietal cell IF R - B12 stomach Duodenum and jejunum Pancreas enzymes R- B12 Enterohepatic circulation B12 B12 IF B12 TC II B12 Ileum cells IF - B12 İleum

41. Functions of Vit.B12 2- Methyl FH4FH4 HomocysteinMethioninSAM B12 Methionin synthase

42. Vit.B12 • Food sources rich in Vit.B12 • Liver • Kidney • Muscle • Egg • Milk ,Cheese and other diary products • Seafood

43. Folic acid Daily requirements Age • 0 - 10 3.6g /kg • > 10 3g /kg • Pregnants 500 g • Lactation +100 g • Diet contains 100 - 500 g folate/day.

44. Folate absorbtion • Mainly jejunum. • In the form of monoglutamate . • Methyltetrahydrofolate monoglutamate is the form it is found in serum .

45. Folate levels: Normal ranges • Serum: 6 – 21 g/L (RBC volume) • Red cell: 160 – 640 g/L (RBC volume) Folate deficiency • Serum folate : <4g /L • Red cell folate: <140g /L

46. Folate stores • Total body folate: 5 – 20 mg • Storage place : Liver • Storage form: Methyl-FH4 polyglutamate

47. Thymidylate synthase Deoxyuridilate DNA-thymine Thymidilate Methylene THFA Dihydrofolate THFA Dihydrofolate reductase serine Methyonine glycine B12 Homocystein Methyl THFA

48. Tissues or organs other than bone marrow are also affected • Skin,GIS, female genital system mucosal epithelium • Congenital abn.(neural tube defects) • Neurologic changes(Vit.B12 deficiency) • Peripheral neuropathy • Subacute combined degeneration of spinal cord • Cerebral -Mental changes • Hyperhomocysteinemia

49. Clinical findings(1) • Anemia: Symptoms of anemia + palor+slight icterus • Glossitis : Sore tongue, poor taste sensation, pain Papill. atrophy-beefy tongue