Hematology PDF - Prenatal and Adult Hematopoiesis

53 HEMATOLOGY by Angela B. Foley...

53 HEMATOLOGY by Angela B. Foley Hematopoiesis Prenatal Hematopoiesis Sac 0 1 2 3 4 5 6 7 8 9 Conception ; Adult Hematopoiesis Months Birth Blood Cell Maturation HEMATOPOIETIC STEM CELL CFU- GEMM CLP COMMITTED CFU-E CFU-GM [EO, BASOJ CFU-MK CFU-TNK & CFU-B PROGENITORS GROWTH FACTORS GM-CSF, GM-CSF, IL-3,5 GM-CSF, IL-1 ,2,4,5,6,7, 12,15 IL-3 EPO IL-3 6,11 , TPO Bone Marrow (BM) Rubriblast Myeloblast Monoblast Megakaryoblast Lymphoblast t t t t t Prorubricyte Promyelocyte Promonocyte Prolymphocyte t t Pmmegl ryocyt, Rubricyte - Myelocyte - t t Metarubricyte Metamyelocyte Megakaryocyte t t Peripheral Blood Reticulocyte t Band Neutrophil t ! EPO CSF TPO = = = Erythropoietin Erythrocyte Colony Stimulating Factor Thrombopoietin Segmented Neutrophil Basophil GM = Monocyte Eosinophil Macrophage (tissue) Granulocyte, monocyte Platelet (thrombocyte) 7\\ NK Cell T Cell B Cell t GEMM = Granulocyte, Erythrocyte, CFU = Colony Forming Unit Plasma Megakaryocyte, Monocyte MK = Megakaryocyte CLP = Committed Lymphoid Progenitor L = Lymphocyte Cell IL ; Interleukin NK ; Nautural Killer 54 3. Protoporphyrin Synthesis a. Precursors (see memory tool below) b. Porphyrias - Enzyme deficiencies cause build-up of heme precursors - r ed or port wine colored urine Action of EPO and TPO ❖ Early precursors (Dl:!,""'LTA ala or PORphobilinogen)- neuropsycluatric symptoms, i.e. acute intermittent porphyria or ID Mature and Immature AIP Cells from Graphic Images ❖ Later precursors (UR, COP, PROTO) - cutaneous sysmptoms such as photosensitivity, facial Hemoglobin hair HEME SYNTHESIS 1. Must have iron and protoporphyrin 2. Iron transport and storage a. Transferrin - Fe transport protein b. Ferritin - major Fe storage form c. Hemosiderin - I-120 insoluble Fe ,;toragP. form (long-tP.rm) Conditiom Associated with lncreaaed Storage of lron d. Excess iron will be stored in tissues and body organs ~ can lead to hemosiderosis, hemochromatosis (organ damage) Fe TraIJBport Protein Fe Storage Forms REMEMBER! Y'ALL ARE HERE AL Heme Precursors ATJ30 R3~10 While in the DELTA, POUR YOUR COP, PRONTO, a cup of HEME. DELTA-aminolevulinic acid t PORphobitinogen t URoporphyrinogen t COProporphyrinogen t PROTOporphyrin t HEME + globin 4 hemoglobin..,_____,,,,, PORPHYRIAS: Exessive formation of porphyrins occurs iJ any enzymatic step in heme synthesis is blocked.  55 Sequence of Conditions Cau.mig- Heme Precursors Left/Bjght Sbifts GLOBIN SYNTHESIS Normal Fetal BD.d Adult HEMOGLOBIN TYPES IN NEWBORN ANO ADULT Hemoglobin Chains CHROMOSOME GLOBIN HGB NEWBORN ADULT CHAINS %.,,~ Basic Laboratory Procedures 16 11 s2 e2 Gower I ANTICOAGULANTS 0% 0% (l2 °2 Gower II (Embryonic) (Embryonic) 1. EDTA (ethylenediamine-tetra-acetate) - chelates Ca++.~: c t e s212 Portland 2. H eparin - anti-thrombin agent cxn2 Hgb F 60-90% 1% HEMOGLOBIN ai&i HgbA2