HAEMOPOIESIS Mohammed Basil .p.a. Second Year BSc MLT Archana madam & Rijo jeckeb joseph sir (Pathology dept.) Erythropoiesis or haemopoiesis is the physiological process of production of RBC. It is mostly place in the bone marrow but it depend upon the stage of life. Life stages Granulocytes Erythrocytes Platelets Lymphocytes Derived from Stem cells .01% - .05% of the marrow cells Stem cells Self renewal Plasticity Progenitor cells Developmentally-restricted cells Mature cells Mature cell production takes place from the more developmentally-restricted progenitors Yolk sac (1-3 month) Liver and spleen (3-6 month) Bone marrow (After birth) Self-renewal Normally in G0 phase of cell cycle The capacity for self-reproduction 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 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 Controlled cell death Controlled cell production There should be a balance between cell production and cell death except at the times of requirement GM-CSF Granulocyte-Macrophage colony stimulating factor M-CSF 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 Cytokines IL 1 (Interleukin 1) IL 3 IL 4 IL 5 IL 6 IL 9 IL 11 TGF-β SCF (Stem cell factor, also known as kit-ligand) Cytokines have no (e.g IL-1) 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 Local environmental control Stromal cell mediated Haemopoiesis Apoptosis Haemopoietic growth factors (Humoral regulation) 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 Lifespan – 120 days Non nucleated Biconcave disc Production regulated by Epo Needs Fe, B12, folate & other elements for development Granulocytes Neutrophils Eosinophils Basophils Only mature cells are present in peripheral blood E N B Neutrophil 2-5 lobe nucleus Primary or secondary granules Pink (azurophilic granules) Grey-blue granules Life 10 hours 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 Larger than lymphocyte Oval or indented nucleus Monocytes >>>>to macrophage Specific function depends on the tissue type 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 Platelet play a major role in primary hemostasis Life span 7-10 days Production, fragmentation of cytoplasm Megakaryocytes undergoes endomitotic division 1/3 in spleen 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