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The Hematopoietic & Lymphoid System

The Hematopoietic & Lymphoid System

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The Hematopoietic & Lymphoid System

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  1. The Hematopoietic & Lymphoid System Dr. Maha Shomaf

  2. Red Cells Disorders • Types : • 1- increase production • 2- decrease production

  3. Anemia • Reduction in oxygen transporting capacity of blood mainly due to reduction of the total red cell mass to below normal amounts .

  4. Causes of anemia : • 1- excessive bleeding • 2- increased RBCs destruction • 3- decreased RBCs production

  5. Anemia due to blood loss • 1- acute : trauma • 2- chronic : GIT lesions & GYN problems

  6. Anemia due to increased destruction (hemolytic anemia) • 1-intrinsic (intracorpuscular) abnormalities). a- hereditary membrane abnormalities enzyme deficiency disorder of Hg synthesis

  7. b- acquired membrane defect (PNH)

  8. 2- Extrinsic (extracorpuscular abnormalities) a- antibodies mediated b- mechanical trauma to RBCs e.g -microangiopathic hemolytic anemias: TTP, DIC -intravascular  Infections: malaria

  9. Anemia due to impaired production • 1-disturbance of proliferation & differentiation of stem cells aplastic anemia, pure red cell aplasia

  10. 2-disturbance of proliferation &maturation of erythroblasts a-defective DNA synthesis: megaloblastic anemias b-defective Hg synthesis    Deficient heme synthesis: iron deficiency anemia   Deficient globin synthesis: thalassemias:      Anemia of renal failure c-unknown or multiple mechanisms

  11. Anemias also can be classified depending on the morphology of the RBCs into : • 1-normocytic • 2-microcytic • 3-macrocytic

  12. Or degree of hemoglobinization into : • 1-Normochromic • 2-Hypochromic • Or RBC shape : • 1-spherocytosis • 2-Ovalocytosis • 3-stomatocytosis • 4-elliptocytosis

  13. Results • 1-Erythroid hyperplasia • 2-Extramedullary hematopoiesis (liver,spleen ,LNs) • 3-Reticulocytosis

  14. RBCs indices are measured by: 1-MCV: the average volume/RBC femtoliters(cubic microns) 2-MCH: the content(mass) of Hg /RBC picogram 3-MCHC:the average concentration of Hg in a given vol. of packed RBCs grams/dl

  15. 4- RDW: red cell distribution width the coefficient of variation of RBC volume 5- HCT(hematocrit): the percentage of RBCs in a known volume of blood

  16. Clinical features of anemia • 1-pallor • 2-fatique • 3-lassitude • 4-hyperbilirubinemia & jaundice • 5-GB stones • 6-secondary hemochromatosis • 7-growth retardation • 8-skeletal abnormalities • 9-cachexia

  17. Anemia of blood loss

  18. Hemmorhage • If acute it can lead to hypovolemic shock • Hemodilution begins at once & full effect within 2-3 days • The anemia is normocytic normochromic • Recovery is inhanced by ↑ erythropoietin level • The marrow response is marked by reticulocytosis

  19. Chronic blood loss is associated with iron deficiency leading to chronic anemia of under production

  20. Anemia of diminished erythropoiesis

  21. Iron deficiency anemia • Anemia affects 25-50% of the population of developing countries &10% of population of developed countries • IDA is the most common cause of nutritional deficiency anemia

  22. Total body iron is 2gms in women 6gms in men • Distribution : 1- 80% in Hg 2- 20% in myoglobin & iron-containing enzymes (catalase &cytochromes)

  23. Iron stores : -Hemosiderin & Fe-binding ferritin contain 10-20% of total body iron -Stored Fe is mainly found in liver ,spleen & BM -Transferrin is 33% saturated with iron normally -serum iron in men is 120 µg/dL in women 100 µg/dL - (TIBC) total iron binding capacity of serum is 300 -350 µg/dL

  24. There is no regulated pathway for iron excretion • 1-2 mg/d are lost by shedding of mucosal & skin epithelial cells • Iron balance is largely regulated by regulating the absorption of dietary iron • Normal daily western diet contains 10-20mg of Fe mostly heme containing animal products & the remainder as inorganic Fe in vegetables

  25. About 20% of heme Fe is absorbable • Only 1-2% of non-heme Fe is absorbable • The average western diet contains sufficientFe to balance the daily loss loss

  26. Iron absorption • Iron is absorbed in duodenum • Nonheme iron is reduced by ferric reductase then transported by the divalent metal transporter (DMT 1) into the cytoplasm • Iron is transferred to transferrin in the plasma through the action of 2 proteins: • 1-ferroportin • 2-hephaestin

  27. Both DMT 1& ferroportin are widely distributed in the body • Only a fraction of the iron that enters the body is deliverd to transferrin by the action of ferroportin • The remainder is bound to ferritin & lost through the exfoliation of mucosal cells

  28. There is balance between the amount of iron deliverd to transfferin & the iron loss • The balance is regulated by hepcidin synthesized by the liver in an iron- dependent fashion • Hepcidin causes degradation of ferroportin & thus when hepcidin level is high less iron is transferred to transferrin

  29. When hepcidin levels are low iron transport is enhanced as in IDA & ineffective erythropoiesis

  30. Causes of iron deficiency anemia • 1-low dietary intake • 2-malabsorption • 3-increased demands not met by increased uptake • 4-chronic blood loss MENORRHAGIA PEPTIC ULCER STOMACH CANCER ULCERATIVE COLITIS INTESTINAL CANCER HAEMORRHOIDS

  31. Clinical manifestation • Mostly asymtomatic • Weakness • Pallor • Glossitis , stomatitis • Dysphagea • Atrophic gastritis • Dry skin • Hair loss

  32. Thinning & spooning of finger nails (koilonychia) • Pica : the compunction to eat non-foodstuffs such as dirt or clay

  33. Stages of IDA • Iron depletion – Stage One • Iron deficient erthyropoiesis – Stage Two • Iron deficiency anemia – Stage Three

  34. Stage 1 (prelatent) • Iron storage is exhausted - indicated by decrease in serum ferritin levels • Hb (N), MCV (N), iron absorption (), transferrin saturation (N), serum ferritin (),marrow iron () • No anemia – RBC morphology is normal • May have elevated RDW

  35. Stage 2 ( Latent ) • Insufficient iron to insert into protoporphyrin ring to form heme • Protoporphyrin accumulates in cell and complexes with zinc to form ZPP • Hb (N), MCV (N), serum ferritin (), transferrin saturation (), TIBC (), • marrow iron (absent) • No anemia, no hypochromia, but slight microcytosis

  36. Stage 3 • All laboratory tests for iron status become abnormal • Most significant finding is microcytic,hypochromic anemia

  37. Diagnosis • Microcytic hypochromic anemia • ↓ MCV & MCHC • ↓ serum ferritin & iron levels • Low transferrin saturation • ↑ TIBC • ↑ platelets • BM cellularity is only mildly increased although erythropoietin is increased • Extramedullary hematopoiesis is uncommon

  38. Adult reference ranges

  39. Normal blood smear

  40. Hypochromic microcytic anemia

  41. Hypochromic microcytic anemia

  42. Thank you

  43. Anemia of chronic disease • The most common type of anemia in hospitalized patients • It is related to inflammation-induced sequestration of iron within the cells of reticuloendothelial system

  44. Causes : 1-chronic microbial infection as - osteomyelitis - bacterial endocarditis - lung abscess 2-chronic immune disorder as RA 3-neoplasms as HD , lung & breast carcinoma

  45. Lab findings • Normocytic normochromic anemia • Or microcytic hypochromic anemia • ↑ iron stores • ↑ serum ferritin • ↓ TIBC