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HAEMOPOEISIS

HAEMOPOEISIS. DEFINITION: [ formation of blood cells from stem cells ] Process which involves origin, development & maturation of Erythrocytes ( ERYTHROPOIESIS) leucocytes ( LEUCOPOIESIS) & platelets ( THROMBOPOIESIS). Theories of hemopoeisis : Monophyletic theory- .(most accepted)

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HAEMOPOEISIS

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  1. HAEMOPOEISIS

  2. DEFINITION: [formation of blood cells from stem cells] • Process which involves origin, development & maturation of • Erythrocytes (ERYTHROPOIESIS) • leucocytes (LEUCOPOIESIS) • & platelets (THROMBOPOIESIS)

  3. Theories of hemopoeisis: Monophyletic theory-.(most accepted) All the cell lines originate from a single precursor- Pluripotent stem cells Polyphyletic theory-. each cell line has a separate precursor stem cell evidence- bone marrow of rat is destroyed using radiation & pluripotent stem cell is injected colonies of all cell lines formed in spleen

  4. Totipotent stem cells- blastocysts of embryo Pluripotent (uncommitted) stem cell- can give rise to any type of blood cell. Best source- umbilical cord blood Committed (progenitor) stem cell- can give rise to a particular cell line

  5. Pluripotent stem cell Committed stem cell of myeloid series Committed stem cells of lymphoid series progenitors BFU-E CFU-E CFU-GM CFU-mega CFU- Eo CFU-B megakaryoblast myeloblast normoblast myeloblast Blast cells myeloblast monoblast lymphocyte Matured cells neutrophil monocyte platelet eosinophil basophil RBC T B

  6. Pluripoient stem cell IL-1,IL-6,IL-3 GM-CSF,G-CSF, SCF Committed pluripotent stem cell Colony forming blastocyte Lymphoid stem cell EP GM-CSF,IL-3,4,5 CFU--E CFU-GM CFU-M granulocyte megakaryocyte L RBC N B E M P

  7. About 75% of cells belong to WBC producing ‘myeloid series’ and only 25% belong to RBC ‘erythroid series’ • Types of differentiation determined by the influence of various ‘Interleukins’ and ‘colony stimulating factors’.

  8. ERYTHROPOISIS • DEFINITION • SITE OF ERYTHROPOIESIS • STAGES OF ERYTHROPOIESIS • CHANGES DURING ERYTHROPOIESIS • FACTORS REGULATING ERYTHROPOIESIS

  9. DEFINITION: production & maturation of RBCs Site of production: A) During intra-uterine life: starts in 3rd week -mesoblastic stage: 3rd week to 3rd month; occurs in mesoderm of yolk sac; intravascular and nucleated RBCs -hepatic stage: 3rd to 5th month; occurs in liver and spleen -myeloid stage: bone marrow starts producing RBCs B) After birth:- exclusively in bone marrow Up to 5yrs- all bones >20yrs- flat bones and ends of long bones.

  10. In fetal life Mesoblastic stage Hepatic stage Myeloid stage

  11. MESOBLASTIC STAGE *btw 3rd week  3rd month • MESENCHYMA OF YOLK SAC • INTRAVASCULAR ERYTHROPOEISIS

  12. HEPATIC STAGE Liver, Spleen and Lymph nodes MYELOID STAGE Red bone marrow

  13. In post natal life: In new born: All bones , red bone marrow (mainly) Liver and spleen In children: Red bone marrow In adults: 18 tp 20yrs- from red bone marrow of skull,vertebrae,ribs,sternum,pelvis

  14. IN NEWBORNS & ADULTS Red Bone Marrow

  15. Red Bone Marrow: hematopoietically active . • The marrow contains both Erythroid (RBC) and leukocyte (WBC) precursors as well as platelet precursors • Yellow Bone Marrow: is inactive, fatty marrow .

  16. Stages of erythropoiesis: • Proerythroblast • Early normoblast • Intermediate normoblast • Late normoblast • Reticulocyte • Mature RBC

  17. Stages of erythropoiesis • Proerythroblast (megaloblast) : • diameter 15-20µ • -cytoplasm basophilic • -nucleus large and occupies most of the cell, distinct nucleoli • -Hb absent • -active mitoses only during stress • -vit B12 & folic acid required for conversion to next stage • Early Normoblast (basophilic erythroblast) : • -diameter 11µ -17µ • -nucleoli absent or rudimentary • -dense nucleus & chromatin • -cytoplasm basophilic • -active mitoses

  18. Intermediate normoblast(polychroamatophil erythroblast) • Diameter 10-14µ • Nucleus often eccentric • No nucleolus • Hb appears at this stage • Cytoplasm-polychromatic (eosinophil staining) • Cell stops division at this stage Late normoblast (orthochromatic erythroblast): • Diameter 7-10µ • No Mitosis • Nucleus assume cartwheel appearance,dense & pyknotic • Nucleus gets extruded or disintegrated • Staining- eosinophil

  19. Reticulocyte • Almost same size as mature RBC(8-9µ) • On vital staining, a network of reticulum seen in cytoplasm • Normal count is about 1% of total RBCs • In New born-2-6% • Haemolysis- 25-30% Mature RBC Diameter-7.2µ Circular & non-nucleated,biconcave disc

  20. RBC (erythrocyte) Normal count-men- 5.4millon/mm3 -women- 4.8millon/mm3 Life span: about 120 days Site of destruction- RES (predominantly in spleen) General changes Reduction in the cell size Disappearance of nucleus Appearance of Hb Changes in staining characteristics Duration:about 7 days

  21. PHSC Pluripotent Hemopoietic stem cell E R Y T H R O P O I E S I S IL-1,IL-6,IL-3 GM CSF erythro BFU-E Burst Forming Unit Erythrocyte CFU-E Colony Forming Unit Erythrocyte GM CSF erythro PROERYTHROBLAST BASOPHILIC ERYTHROBLAST POLYCHROMATOPHILIC ERYTHROBLAST ORTHOCHROMATIC ERYTHROBLAST RETICULOCYTE ERYTHROCYTE ERYTHROCYTE

  22. ERYTHROPOIESIS 15-20µm- basophilic cytoplasm, nucleus with nucleoli. 14-17µm-mitosis, basophilic cytoplasm, nucleoli disappears. 10-15µm-’POLYCHROMASIA’ Hb appears, nucleus condenses. 7-10µm- PYKNOTIC Nucleus. Extrusion, Hb is maximum. 7.3µm- Reticulum of basophilic material in the cytoplasm. 7.2µm- Mature red cell with Hb.

  23. PROERYTHROBLAST 5 DAYS RETICULOCYTE 2 DAYS RED BLOOD CELLS

  24. Factors affecting erythropoises

  25. Regulation of Erythropoiesis Maturation Factors General Factors • Dietary Factors • Castles intrinsic Factor • Extrinsic Factor Hypoxia

  26. Internal External hormonal Maturation factor Others Hb • Interleukins • CSFs • Erythropoietin • Androgen • Oestrogen • Thyroxine • Growth hormone • Cortisol • Iron • Copper • Cobalt • Proteins • VitB12 • Folic acid Intrinsic factor Cyanocobalamine

  27. ABSORPTION OF VITAMIN B 12 Intrinsic Factor + Vitamin B12 Vitamin B12 (in a bound state protected by gastric enzymes) Binds to mucosal cells of ileum Absorbed into blood by pinocytosis

  28. Formation and release of erythropoietin: Kidney Liver Hypoxia Renal erythropoietic factor (Erythrogenin) Erythropoietinogen Erythropoietin Erythropoietin (  globulin) Erythropoietin stem cell Proerythroblasts

  29. ERYTHROPOEITIN • Stimuli for production • hypoxia, • high altitude, • anemia, • chronic lung or heart diseases, • catecholamines, • prostaglandins & • androgens. • Formed in hours, RBC’s take 2-3 days to appear in peripheral blood.

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