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ERYTHROPOIESIS

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PROCESS OF FORMATION OF RBC

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ERYTHROPOIESIS

  1. 1. DR NILESH KATE MBBS,MD ASSOCIATE PROF DEPT. OF PHYSIOLOGY ERYTHROPOIESIS.
  2. 2. OBJECTIVES  Sites of haemopoiesis.  Blood cell precursors.  Control of haemopoiesis.  Stages of erythropoiesis.  Regulation of erythropoiesis  Factors necessary for erythropoiesis Monday, December 7, 2015
  3. 3. HAEMOPOIESIS.  Process of development of blood cells.  Erythropoiesis – development of RBC  Leucopoiesis – Development of WBC  Thrombopoiesis – Development of platelets. Monday, December 7, 2015
  4. 4. SITES OF HAEMOPOIESIS.  First 2 months of gestation – yolk sac.  3rd month onwards – liver 7 spleen.  20th week onwards – till birth - bone marrow. Monday, December 7, 2015
  5. 5. SITES OF HAEMOPOIESIS.  In Young Children – axial skeleton & bones of extremities i.e. Red Bone marrow.  With fatty replacement it becomes Yellow Bone Marrow.  In Adults – axial skeleton & proximal extremities of long bones.  In Pathological conditions – extra medullary haemopoiesis i.e liver & spleen resumes . Monday, December 7, 2015
  6. 6. BLOOD CELL PRECURSORS.  The stem cells – Monophyletic Theory.  All originate from PHSC, Pleuripotent Hamopoietic Stem Cell.  Fundamental properties  Self replication.  Differentiation & commitment. Monday, December 7, 2015
  7. 7. BLOOD CELL PRECURSORS.  Progenitor cells.  Pleuripotent progenitor cells  Lymphoid stem cell – Lymphocytes.  Myeloid stem cell.  Granulocyte – Monocyte progenitor.  Erythroid progenitor.  Megakaryocyte Progenitor. Monday, December 7, 2015
  8. 8. FEATURES OF PROGENITOR CELLS.  Progenitor cells form group of cells called Clones so also called CFU-colony forming units.  CFU-GEMM – Granulocyte, Erythroid, Megakaryocyte & Macrophages.  BFU-E – Burst forming units Erythroid.  CFU-E - Erythroid  CFU-Ba – Basophil. Monday, December 7, 2015
  9. 9. CONTROL OF HAEMOPOIESIS.  Mainly by Hamopoietic Growth Factors i.e. Cytokines.  These are called Colony Stimulating Factors (CSF)  CSF-G  CSF-M  CSF-GM  Interleukins – for Lymphocyte precursor.  Erythropoietin Monday, December 7, 2015
  10. 10. Monday, December 7, 2015
  11. 11. STAGES OF ERYTHROPOIESIS.  Pronormoblast  Early normoblast (Basophilic)  Intermediate normoblast (Polychromatic)  Late normoblast (orthochromatic)  Reticulocyte. Monday, December 7, 2015
  12. 12. Monday, December 7, 2015 STAGES OF ERYTHROPOIESIS.
  13. 13. Monday, December 7, 2015 CELLS/FEATURES SIZE CYTOPLASM NUCLEUS HAEMOGLOB IN MITOSIS PRONORMOBLAS T 15-20 μm BASOPHILIC LARGE WITH RETICULAR FORMATION ABSENT SEEN EARLY 12- 16μm BASOPHILIC LARGE,NUCL EOLI DISAPPEARE D. ABSENT SEEN INTERMEDIATE 10- 14μm POLYCHROM ATIC CONDENSED APPEARS PRESENT LATE 8-10μm ACIDOPHILI C SMALL PYKNOTIC INCREASES ABSENT RETICULOCYTE 7- 7.5μm RETICULUM LIKE ABSENT INCREASES ABSENT
  14. 14. MATURATION OF RETICULOCYTE TO ERYTHROCYTES.  Reticulocyte – juvenile red cells without nucleus but contains ribosomal RNA so can synthesize Hb.  Mature Red cells maturation in spleen, lost Ribosomes, Mitochondria.  Reticulocyte in Infants -2-6%, Adults 0.5-2%.  Slightly basophilic hue in cytoplasm & can stain with new Methelene Blue or Brilliant Cresyl Blue Monday, December 7, 2015
  15. 15. SUMMARY OF CHANGES. Cell Duration Size Nucleus Hb synthesis Cytoplas m staining Mitosis Reticuloc yte 0-5 DAYS 7-7.5 μm Condens es, pyknotic Present Basophili c- polychro matic - acidophil ic Only upto intermed iate normobl ast RBC 2 DAYS 7 μm Absent Absent acidophil ic Absent only cell matures. Monday, December 7, 2015
  16. 16. REGULATION OF ERYTHROPOIESIS  Erythropoietin – Glycoprotein with molecular wt 34000.  Site of formation-  85% - epithelial linings of peritubular capillaries.  15% - liver & cells of tissue macrophage system. Monday, December 7, 2015
  17. 17. ERYTHROPOIETIN  Stimulus for secretion.  Mainly hypoxia – causes release of Renal Erythropoietic Factor – acts on Plasma alpha globulin Erythropoietinogen – form Erythropoietin Monday, December 7, 2015
  18. 18. ERYTHROPOIETIN  Actions  Main effect on stem cells – differentiation  Promote Hb synthesis  Promotes every stage  Promotes release of RBC from Bone Marrow to Peripheral Circulation. Monday, December 7, 2015
  19. 19. FACTORS AFFECTING ERYTHROPOIETIN  Increase secretion  Hormones – Androgen , Thyroxine, GH, ACTH, Prolactin, Adrenocortical Steroids.  Haemolysates – products of RBC destruction.  Nucleotides – cAMP,NAD,NADP  Vasoconstrictor drugs – that causes renal hypoxia  Decrease secretion.  Adenosine antagonists – Theophylline.  Oestrogen – decreases synthesis of Globin & depressing erythropoietic response to hypoxia. Monday, December 7, 2015
  20. 20. Monday, December 7, 2015
  21. 21. FACTORS NECESSARY FOR ERYTHROPOIESIS  General factors.  Special maturation factors.  Haemoglobinization factors. Monday, December 7, 2015
  22. 22. GENERAL FACTORS.  Optimum levels of hormone Erythropoietin & efficient feedback mechanism controlling erythropoietin. Monday, December 7, 2015
  23. 23. SPECIAL MATURATION FACTORS.  Vit B 12 (extrinsic factor)  Folic acid  Intrinsic factor of Castle. Monday, December 7, 2015
  24. 24. VIT B 12 (EXTRINSIC FACTOR)  Vit B12 – Cyanocobalamin or extrinsic factor.  Daily need – 1-2 μg.  Sources – Milk, Meat, Liver of Animals  Also synthesized by bacterial Flora. Monday, December 7, 2015
  25. 25. VIT B 12 (EXTRINSIC FACTOR)  ABSORPTION – need Intrinsic Factor Of Castle , a glycoprotein secreted by parietal cells of gastric mucosa.  With it form Intrinsic Factor- Cyanocobalamin complex  Bound to sp receptors in ileum & absorbed by Endocytosis. Monday, December 7, 2015
  26. 26. VIT B 12 (EXTRINSIC FACTOR)  TRANSPORT – in blood transported by combining with Transcobalamin-II  STORAGE – In liver & Muscle  ROLE – required for synthesis of DNA & maturation of nucleus & cell. Monday, December 7, 2015
  27. 27. FOLIC ACID  Folic acid – Pteroylglutamic acid.  Daily requirement – 100 μg.  Sources – leafy veg, pulses, yeasts, liver.  From breakdown of Polyglutamate to Monoglutamates. Monday, December 7, 2015
  28. 28. ROLE OF FOLIC ACID IN DNA SYNTHESIS. Monday, December 7, 2015 Polyglutamates in food Monoglutamates Plasma Methyl tetrahydrofolate TetraHydrofolate (THF) Formyl THF(Folinic Acid) 5,10 methylene THF Dihydrofolate Uridine Monophosphate D Thymidine Monophosphate Dihydro reductase
  29. 29. INTRINSIC FACTOR OF CASTLE.  Intrinsic factor of Castle is formed by Gastric Cells.  Deficiency if intrinsic factor occurs in autoimmune cause of failure of secretion of IF. ( Addisonian Pernicious Anaemia) Monday, December 7, 2015
  30. 30.  Thank you. Monday, December 7, 2015

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