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Normal Haemopoiesis 3.57.51 PM

Normal Haemopoiesis 3.57.51 PM - Normal Haemopoiesis Dr...

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Unformatted text preview: Normal Haemopoiesis Dr. Tariq M. Roshan Department of Hematology PPSP Introduction Introduction Life span Granulocytes Erythrocytes Platelets Lymphocytes Derived from Stem cells .01% ­ .05% of the marrow cells Introduction Introduction Stem cells Self renewal Plasticity Progenitor cells Developmentally­restricted cells Mature cells Mature cell production takes place from the more developmentally­restricted progenitors Cell hierarchy (Haemopoiesis Cell hierarchy (Haemopoiesis schematic representation) Sites of Haemopoiesis Sites of Haemopoiesis Yolk sac Liver and spleen Bone marrow – Gradual replacement of active (red) marrow by inactive (fatty) tissue – Expansion can occur during increased need for Stem cells Stem cells Self­renewal Normally in G0 phase of cell cycle The capacity for self­reproduction is vastly in excess of that required to maintain cell production for normal lifetime As cells increase in number they differentiate as well Multipotentiality Capacity to generate cells of all the lymphohaemopoietic lineages Interaction of stromal cells, growth Interaction of stromal cells, growth factors and haemopoietic cells Progenitor cells Progenitor cells Encompasses from immediate progeny of stem cells to cells committed to one differentiation lineage Progenitor cells become progressively more restricted in their differentiation and proliferation capacity Late progenitor cells eventually restricted to one lineage Regulation of Haemopoiesis Regulation of Haemopoiesis Controlled cell death Controlled cell production There should be a balance between cell production and cell death except at the times of requirement Local and Humoral regulation of Local and Humoral regulation of Haemopoiesis Haemopoietic growth factors Haemopoietic growth factors GM­CSF Granulocyte­Macrophage colony stimulating factor M­CSF Macrophage colony stimulating factor Erythropoietin Erythropoiesis stimulating hormone (These factors have the capacity to stimulate the proliferation of their target progenitor cells when used as a sole source of stimulation) Thrombopoietin Stimulates megakaryopoiesis Haemopoietic growth factors Haemopoietic growth factors Cytokines IL 1 (Interleukin 1) IL 3 IL 4 IL 5 IL 6 IL 9 IL 11 TGF­β SCF (Stem cell factor, also known as kit­ligand) Cytokines have no (e.g IL­1) or little (SCF) capacity to stimulate cell proliferation on their own, but are able to synergise with other cytokines to recruit nine cells into proliferation Role of growth factors in normal Role of growth factors in normal haemopoiesis Regulation of Haemopoiesis Regulation of Haemopoiesis Local environmental control Stromal cell mediated Haemopoiesis Apoptosis Haemopoietic growth factors (Humoral regulation) Apoptosis Apoptosis Regulated physiological cell death Homeostasis Morphological evidence Enzymatic digestion of DNA and cell disintegration Caspases Endonuclease Two major pathway of activation of caspases Membrane signalling Cytochrome c release Mechanism; apoptosis Mechanism; apoptosis Erythropoiesis and erythrocytes Erythropoiesis and erythrocytes Lifespan – 120 days Non nucleated Biconcave disc Production regulated by Epo Needs Fe, B12, folate & other elements for development Development of mature red cells Development of mature red cells Granulopoiesis Granulopoiesis Granulocytes E – Neutrophils – Eosinophils – Basophils Onlymature cells are present in peripheral blood N B Granulopoiesis Granulopoiesis Neutrophil – 2­5 lobe nucleus – Primary or secondary granules Pink (azurophilic granules) Grey­blue granules – Life 10 hours Precursors – – – – – Myeloblast <4% Pro myelocytes Myelocytes Metamyelocytes Band form (stab form) Neutrophil kinetics Neutrophil kinetics Granulopoiesis Eosinophils – Coarser & more deeply red staining granules – Rarely more than two lobes of nucleus – Special role in allergy, inflamation & parasite infection Basophils – Occasionally seen – Dark cytoplasmic granules – Role in hypersensitivity response – Give rise to mast cells Monocytes Monocytes Larger than lymphocyte Oval or indented nucleus Monocytes >>>>to macrophage Specific function depends on the tissue type Lymphopoiesis Lymphopoiesis Immunologically competent cells Primary lymphoid organs Bone marrow Thymus Secondary lymphoid organs Lymph nodes Spleen Lymphoid tissues Lymphocytes B and T lymphocytes NK killer cells Lymphopoiesis Lymphopoiesis Thrombopoiesis Thrombopoiesis Platelet play a major role in primary hemostasis Life span 7­10 days Production, fragmentation of cytoplasm Megakaryocytes undergoes endomitotic division 1/3 in spleen Summary Summary Normal haemopoiesis is necessary for the survival It is under the control of multiple factors Normal bone marrow environment is necessary for normal haemopoiesis Decreased production results in cytopenias ...
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