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hematology hematopoiesis l.
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HEMATOLOGY

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HEMATOLOGY

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  1. HEMATOLOGY/HEMATOPOIESIS Introduction

  2. HEMATOLOGYIntroduction • Study of blood & its components • Window of rest of body

  3. BLOODRaison d’etre • Delivery of nutrients • Oxygen • Food • Vitamins • Removal of wastes • Carbon dioxide • Nitrogenous wastes • Cellular toxins • Repair of its conduit • Protection versus invading microorganisms • Multiple cellular & acellular elements

  4. HEMATOLOGYDivisions • Red Blood Cells/Oxygen & CO2 transport • White Blood Cells/Protection versus microorganisms • Coagulation/platelets/Maintenance of vascular integrity

  5. HEMATOLOGYHematopoiesis • In humans, occurs in bone marrow exclusively • All cellular elements derived from pluripotent stem cell (PPSC) • PPSC retains ability to both replicate itself and differentiate • Types of differentiation determined by the influence of various cytokines

  6. HEMATOPOIESIS Committed Stem Cells

  7. RED BLOOD CELLSIntroduction • Normal - Anucleate, highly flexible biconcave discs, 80-100 femtoliters in volume • Flexibility essential for passage through capillaries • Major roles - Carriers of oxygen to & carbon dioxide away from cells

  8. ERYTHROPOIETIN • Cytokine - Produced in the kidney • Necessary for erythroid proliferation and differentiation • Absence results in apoptosis (programmed cell death) of erythroid committed cells • Anemia of renal failure 2° to lack of EPO

  9. ERYTHROPOIETINMechanism of Action

  10. ERYTHROPOIETINMechanism of Action • Binds specifically to Erythropoietin Receptor • Transmembrane protein; cytokine receptor superfamily • Binding leads to dimerization of receptor • Dimerization activates tyrosine kinase activity

  11. ERYTHROPOIETINMechanism of Action • Multiple cytoplasmic & nuclear proteins phosphorylated • Nuclear signal sent to activate production of proteins leading to proliferation and differentiation

  12. ERYTHROPOIETINRegulation of Production

  13. ErythropoietinResponse to Administration rhuEPO 150 u/kg 3x/wk

  14. RBC Precursors • Pronormoblast • Basophilic normoblast • Polychromatophilic Normoblast • Orthrochromatophilic Normoblast • Reticulocyte • Mature Red Blood Cell • 5-7 days from Pronormoblast to Reticulocyte

  15. RBC Assessment • Number - Generally done by automated counters, using impedance measures • Size - Large, normal size, or small; all same size versus variable sizes (anisocytosis). Mean volume by automated counter • Shape - Normal biconcave disc, versus spherocytes, versus oddly shaped cells (poikilocytosis) • Color - Generally an artifact of size of cell

  16. Red Blood CellsNormal Values

  17. RETICULOCYTE • Young red blood cell; still have small amounts of RNA present in them • Tend to stain somewhat bluer than mature RBC’s on Wright stain (polychromatophilic) • Slightly larger than mature RBC • Undergo removal of RNA on passing through spleen, in 1st day of life • Can be detected using supravital stain • Important marker of RBC production

  18. RETICULOCYTE COUNTAbsolute Value • = Retic % x RBC Count • eg 0.01 x 5,000,000 = 50,000 • Normal up to 100,000 • More accurate way to assess body’s response to anemia

  19. ANEMIACauses • Blood loss • Decreased production of red blood cells (Marrow failure) • Increased destruction of red blood cells • Hemolysis • Distinguished by reticulocyte count • Decreased in states of decreased production • Increased in destruction of red blood cells

  20. RBC DESTRUCTION - EXTRAVASCULARMarkers • Heme metabolized to bilirubin in macrophage; globin metabolized intracellularly • Unconjugated bilirubin excreted into plasma & carried to liver • Bilirubin conjugated in liver &excreted into bile & then into upper GI tract • Conjugated bilirubin passes to lower GI tract & metabolized to urobilinogen, which is excreted into stool & urine

  21. RBC DESTRUCTION - INTRAVASCULAR • Free Hemoglobin in circulation leads to • Binding of hemoglobin to haptoglobin, yielding low plasma haptoglobin • Hemoglobin filtered by kidney & reabsorbed by tubules, leading to hemosiderinuria • Capacity of tubules to reabsorb protein exceeded, yielding hemoglobinuria

  22. INTRAVASCULAR HEMOLYSIS

  23. HEMOLYTIC ANEMIACommonly used Tests Problems with sensitivity & specificity