ERYTHROPOIESIS. Development of RBC s. 03-Dec-17. Before Birth (EMBRYO) Before Birth (EMBRYO) After Birth. MESOBLASTIC STAGE 1 st Trimester

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1 Development of RBC s ERYTHROPOIESIS Before Birth (EMBRYO) Prof Dr Waqas Hameed HOD, Physiology Pak Int l Medical College After Birth Before Birth (EMBRYO) MESOBLASTIC STAGE 1 st Trimester Yolk Sac Capillary Endothelium HEPATIC STAGE 2 nd Trimester Liver / Spleen MYELOID STAGE 3 rd Trimester Bone Marrow 1

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3 Cell Pro Early Size μm Mitochondria Nucleus Cytoplasm Hb Large (3/4) of cell Chromatin fine strippled Nucleoli present Chromatin small No nucleoli Little cytoplasm Small Mitochondria Cytoplasm s Mitochondria ve _ Intermediate Late _ Chromatin further Very small Chromatin Pyknotic Reticulocyte 8 _ Absent nucleus Mature RBC 7.2 _ Absent nucleus POLYCHROMATIC Basophilia s Mitochondria reduce but ve (ORTHO CHROMIC (Eosinophilic) Basophilia Mitochondria ve RETICULAR (RNA) Basophilia Mitochondria Very Small PALE YELLOW No DNA & RNA No Mitochondria, No Basophilia No Hb Synthesis (65%) (100%) Cell Pro Early Size μm Mitochondria Nucleus Cytoplasm Hb Large (3/4) of cell Chromatin fine strippled Nucleoli present Chromatin small No nucleoli Little cytoplasm Small Mitochondria Cytoplasm s Mitochondria ve _ Intermediate Late _ Chromatin further Very small Chromatin Pyknotic Reticulocyte 8 _ Absent nucleus Mature RBC 7.2 _ Absent nucleus POLYCHROMATIC Basophilia s Mitochondria reduce but ve (ORTHO CHROMIC (Eosinophilic) Basophilia Mitochondria ve RETICULAR (RNA) Basophilia Mitochondria Very Small PALE YELLOW No DNA & RNA No Mitochondria, No Basophilia No Hb Synthesis (65%) (100%) 3

4 Cell Pro Early Size μm Mitochondria Nucleus Cytoplasm Hb Large (3/4) of cell Chromatin fine strippled Nucleoli present Chromatin small No nucleoli Little cytoplasm Small Mitochondria Cytoplasm s Mitochondria ve _ Intermediate Late _ Chromatin further Very small Chromatin Pyknotic Reticulocyte 8 _ Absent nucleus Mature RBC 7.2 _ Absent nucleus POLYCHROMATIC Basophilia s Mitochondria reduce but ve (ORTHO CHROMIC (Eosinophilic) Basophilia Mitochondria ve RETICULAR (RNA) Basophilia Mitochondria Very Small PALE YELLOW No DNA & RNA No Mitochondria, No Basophilia No Hb Synthesis (65%) (100%) Cell Pro Early Size μm Mitochondria Nucleus Cytoplasm Hb Large (3/4) of cell Chromatin fine strippled Nucleoli present Chromatin small No nucleoli Little cytoplasm Small Mitochondria Cytoplasm s Mitochondria ve _ Intermediate Late _ Chromatin further Very small Chromatin Pyknotic Reticulocyte 8 _ Absent nucleus Mature RBC 7.2 _ Absent nucleus POLYCHROMATIC Basophilia s Mitochondria reduce but ve (ORTHO CHROMIC (Eosinophilic) Basophilia Mitochondria ve RETICULAR (RNA) Basophilia Mitochondria Very Small PALE YELLOW No DNA & RNA No Mitochondria, No Basophilia No Hb Synthesis (65%) (100%) 4

5 Cell Pro Early Size μm Mitochondria Nucleus Cytoplasm Hb Large (3/4) of cell Chromatin fine strippled Nucleoli present Chromatin small No nucleoli Little cytoplasm Small Mitochondria Cytoplasm s Mitochondria ve _ Intermediate Late _ Chromatin further Very small Chromatin Pyknotic Reticulocyte 8 _ Absent nucleus Mature RBC 7.2 _ Absent nucleus POLYCHROMATIC Basophilia s Mitochondria reduce but ve (ORTHO CHROMIC (Eosinophilic) Basophilia Mitochondria ve RETICULAR (RNA) Basophilia Mitochondria Very Small PALE YELLOW No DNA & RNA No Mitochondria, No Basophilia No Hb Synthesis (65%) (100%) Reticulocytes 1% Help evaluate Bone Marrow s ability to produce RBC c 5

6 Summary of RBC formation Reticulocyte Cell size Cytoplasm become more extensive Nucleoli disappear Mitochondria disappears Chromatin become progressively coarser Cytoplasm become less basophilic due to in RNA Mature RBC Factors Affecting Erythropoiesis Growth Inducers Differentiation Inducers 6

7 STEM CELL FACTOR (SCF) CYTOKINES Interleukin 1 Interleukin 6 Interleukin 3 GRANULOCYTE & MACROPHAGE COLONY STIMULATING FACTORS GM-CSF (granulocyte macrophage colony stimulating factor G-CSF (granulocyte colony stimulating factor M-CSF (macrophage colony stimulating factor ERYTHROPOIETIN Glycoprotein MW 34,000 Circulating hormone Site of synthesis: Kidneys 90% (interstitial cells in peritubular capillary bed) Liver 10% (perivenous hepatocytes) 7

8 Erythropoietin contd. Stimulus Hypoxia High Altitude Lung diseases Cardiac failure ERYHTROPOIETIN s no. of erythropoietin sensitive committed stem cells Stimulates production of Proerythroblasts from hematopoietic stem cells in bone marrow 8

9 Factors requires for Erythropoiesis contd. Vitamin B 12 (Cyanocobalamin) & Folic Acid Essential for synthesis of DNA Lack failure of nuclear maturation & cell division Maturation Failure Larger than normal cells produced MACROCYTES Flimsy / Irregular cell membrane Oval shape Short life - half to one third normal DIET First class proteins amino acid synthesis IRON Essential for Hemoglobin synthesis Deff. anemia COPPER & MANGANESE Impaired metabolism of iron COBALT Deff. anemia Constituent of Vit. B 12 Factors requires for Erythropoiesis contd. HORMONES THYROXINE levels - production of RBC s ( bone metabolism) ANDROGENS (TESTOSTERONE) Stimulate erythropoiesis GLUCOCORTICOIDS Stimulate erythropoiesis Factors requires for Erythropoiesis contd. synthesis of Erythropoietin 9

10 Jazak Allah 10