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4. Erythropoesis - dental.pptx
- 1. HAEMOPOIESIS •Development of blood cells •Erythropoiesis – RBCs (Process of formation and maturation of RBCs ) •Leucopoesis – WBCs •Megakaryopoesis- Platelets
- 2. Sites of haemopoiesis 1.Intrauterine life : 3 stages A) Mesoblastic stage : up to 3 week of foetal life Mesoderm of the yolk sac B) Hepatic stage : From 3 rd week –to 6m Liver, spleen C) Myeloid stage : From 6 mths – full term Red Bone Marrow 2) In children : Upto 6yrs marrow of all bones 3) In Adults : Upto 20yrs long bones ,vertebrae, skull ,Ribs, Sternum, ilia After 20yrs: Upper ends of long bones, vertebrae, ribs, sternum, ilia
- 3. Bone Marrow The bone marrow - one of the most active organs Active BM: red marrow- cells at different stages of development… Inactive BM infiltrated with fat: yellow marrow • BM is aspirated from iliac bone/sternum….properly stained…examined under microscope.. • Indications: anemia..leukemia, lymphoma, pancytopenia
- 5. Bone Marrow…. • 75% of the cells in the marrow belong to the myeloid series ( for WBC & Platelets) • Only 25% - red cells. • Normal myeloid- erythroid ratio is 3:1 • In circulation RBC count is 500 times more than WBC count…because of longer life span of RBCs…
- 6. PPSC → COMMITTED STEM CELLS BFU -E ↓ CFU – E ↓ PROERYTHROBLAST ↓ EARLY NORMOBLAST ↓ INTERMEDIATE NORMOBLAST ↓ LATE NORMOBLAST ↓ RETICULOCYTE ↓ ERYTHROCYTE Stages Of Erythropoesis
- 7. Proerythroblast / Pronormoblast • First identifiable cell of erythroid series • Cell size – 15- 20 micrometer • Nucleus occupies 3/4TH of cell volume with multiple nucleoli • Chromatin threads present • Cytoplasm – basophilic (high concentration of polyribosomes) • Mitosis – present • Hb – absent
- 8. Early Normoblast /Basophilic Normoblast • 14 – 16 micrometer • Nucleus size – decrease –nucleoli absent • Chromatin condensation present • Cytoplasm – basophilic • Mitosis – present • Hb – absent
- 9. Intermediate Normoblast (Polychromatophilic normoblast ) • Cell size – decrease – 10 – 14 micrometer • Nucleus size – decrease • Hb – starts appearing • Cytoplasm –Polychromatophilic • – bluish and pinkish (basophilic RNA & acidophilic Hb) • Mitosis – present
- 10. Late Normoblast/Orthochromatic Normoblast • 8 – 10 micrometer • Eccentric cart wheel nucleus • Pyknotic degeneration- clumping of the chromosomes, shrinking of the nucleus. • Cytoplasm - reddish (Acidophilic) • No mitosis • Hb – present • Nucleus is extruded out later
- 11. Reticulocyte • Cell size decrease 7 – 8 micrometer • Nucleus absent • RNA appears as a reticulum on Supravital Staining (with Brilliant Cresyl Blue) • Hb increased • Reticulocyte spends 1-2 days in bone marrow and 1-2 days in the peripheral blood..spleen ..matures into biconcave RBC • Mitochondria, ribosomes etc are lost when converted to RBCs…so RBC cannot synthesize proteins..
- 12. Reticulocyte….. •Normal count: In infants: 2-6% of RBC count Adult - 0.5 to 1% of RBC count Reticulocytosis • Physiological – at birth, infants ,high altitude • Pathological – hemolytic anemia • Reticulocytopenia – Aplastic anemia
- 13. Erythrocyte • Cell size – 7.2- 7.5 micrometer • Absence of RNA material, no organelles • One Pronormoblast give rise to at least 8-10 RBCs • 2 million RBCs produced each sec • Average duration of Erythropoiesis: 7 to 9 days Proerythroblast to reticulocyte takes 5 to 7 days Maturation of reticulocyte to RBC takes 2 days.. • Life span = 120days
- 15. Factors Affecting Erythropoesis General factors - Hypoxia Erythropoietin - Growth inducers - Hormones Maturation factors - Iron, Vitamin B 12,Folic acid Factors necessary for hemoglobin production - Vitamin C Helps in iron absorption (Fe3+ Fe2+) - Proteins Amino Acids for globin synthesis - Iron, copper, cobalt & nickel Heme synthesis
- 16. 1.ERYTHROPOETIN ( EPO) • Glycoprotein. Formation • 85% formed in endothelial cells of the peritubular capillaries of the renal tubules. • 15% formed in liver Breakdown In liver. Half life is 5 hours PTC
- 17. Renal tissue hypoxia tissue levels of Hypoxia-inducible Factor-1 (HIF-1), HIF-1 binds to a hypoxia response element in the Erythropoietin gene, Transcription of messenger RNA and, increased Erythropoietin synthesis
- 18. Stimuli increasing EPO Hypoxia is the potent stimulus High altitude Anemia Chronic lung or heart diseases Catecholamines Androgens •Decreased by Estrogen
- 19. Functions of EPO Erythropoietin increases RBC production - • Stimulates stem cells towards erythroid series • Promotes pronormoblast production from progenitor cells • Enhances mitosis • Accelerates Hb synthesis • Promotes the early release of reticulocytes. Applied – EPO injections in treatment of anemia in renal failure
- 20. 2.Growth inducers/ Differentiation inducers • Interleukin 1, 3, 5 (IL-3 is a growth inducer for all cell lines ) Acts on stem cells to convert them to progenitor cells • Colony stimulating factors – produced from T cells, endothelial cells, fibroblasts stimulates production of committed stem cells . 3. Hormones •Androgens & Estrogen Erythropoesis •. Thyroxine , GH, Cortisol –stimulates Erythropoesis
- 21. Maturation factors Role of iron ,folic acid & vitamin B12. • Iron- needed for Hb synthesis • Folic acid & Vit B12- required for the synthesis of DNA and maturation of nucleus and cell. • Milk ,meat ,liver ,Green leafy vegetables If deficiency occurs… failure of maturation of nucleus. There occurs reduction in the cell division. Cells remain large (megaloblasts) and become more fragile. • Intrinsic factor – needed for Vit B12 absorption
- 22. Other dietary factors •Vitamin C Helps in iron absorption (Fe3+ Fe2+) •Proteins Amino Acids for globin synthesis •Copper, cobalt & nickel. Heme synthesis (Copper- incorporation of Fe into Porphyrin Ring )