Haematology Lecture 2 PDF

16 January 2023 HEMATOLOGY Haematopoiesis By :Abdulfatah albakkosh 16-Jan-23 LECTURE 2 1 Definition:  Haematopoiesis: is the production of the various types of blood cells.  To maintenance of an adequate number of cells in the circulation (post- mitotic) and depends on the proliferation of p...

16 January 2023 HEMATOLOGY Haematopoiesis By :Abdulfatah albakkosh 16-Jan-23 LECTURE 2 1 Definition:  Haematopoiesis: is the production of the various types of blood cells.  To maintenance of an adequate number of cells in the circulation (post- mitotic) and depends on the proliferation of precursor cells that still retain mitotic capability.  This process is regulated by cytokines (growth factors) and takes place in specialized microenvironment.  The hematopoiesis take place in the hematopoietic organs( which confined to bone marrow in adults). 16-Jan-23 LECTURE 2 2 16 January 2023 HEMATOLOGY • The replacement of circulating mature blood cells (incapable of mitosis) and they have limited life span depends on function of the hematopoietic precursor cells (proliferative capabilities). • It depends on careful balance between cellular proliferation, cellular differentiation and cell death(apoptosis). 16-Jan-23 LECTURE 2 3 • Hematopoiesis: • Erythropoiesis: formation of red blood cells. • Leukopoiesis: formation of white blood cells. • Thrombopoiesis: formation of platelet. 16-Jan-23 LECTURE 2 4 16 January 2023 HEMATOLOGY Stages of hematopoiesis Bone marrow spleen Liver 0 1 2 3 4 5 Prenatal period ( months ) 6 7 8 9 Birth Yolk sac Postnatal Period 16-Jan-23 LECTURE 2 5 16-Jan-23 LECTURE 2 6 16 January 2023 HEMATOLOGY 16-Jan-23 LECTURE 2 7 Definition: • Proliferation: cell division • Differentiation: generating the diverse cell population that provide the specialized functions needed by the organism • Maturation: formation of mature cells of particular type. • Commitment : when two cells derived from the same precursor take a separate route of development. 16-Jan-23 LECTURE 2 8 16 January 2023 HEMATOLOGY Diagram showing the development of different blood cells from haematopoietic stem cell to mature cells 16-Jan-23 LECTURE 2 9 Hematopoietic cells: • Hematopoietic precursor cells can be divided into three cellular compartment: stem cells, progenitor cells, maturing cells. 1- stem cells: • All hematopoiesis derives from a pool of undifferentiated stem cells, which give rise to all of the bone marrow cells by the process of proliferation and differentiation. • Constitute only 0.5% of the total marrow nucleated cells. • Defined as pluripotential( give all lineages of blood cells) 16-Jan-23 LECTURE 2 10 16 January 2023 HEMATOLOGY Hematopoietic cells : • Self –renewal (capacity give raise to daughter stem cells that are exact replicate of parent cell). 2-progenitor cells: • It includes all precursors cells located between stem cells morphologically recognizable precursor cells. • Constitute 3% of the total nucleated hematopoietic cells, • Restricted development potential (multipotential, unipotential). 16-Jan-23 LECTURE 2 11 2-progenitor cells: • In culture media the progenitor cells are called colony-forming units (CFUs), thus • CFUGEMM: multipotent hematopoietic progenitor cell that produce granulocytes, erythroblasts, monocytes, and megakaryocytes. • CFUGM: bipotent is the more mature and specialized precursor cells that give rais to both granulocytic and monocytic • CFUEO, CFUBa, CFUE, and CFUMeg.:unipotent progenitor cells. 16-Jan-23 LECTURE 2 12 16 January 2023 HEMATOLOGY Hematopoietic cells : • With out self-renewal. • Not morphologicall recognizable( measured by clonal assay in vitro) • 3- maturing cells: • Constitute more than 95% of the total hematopoietic cells. • Morphologically recognizable. • The capacity of proliferation is lost before full maturation of these cells is complete. 16-Jan-23 LECTURE 2 13 Cytokines and the control of hematopoiesis: • Hematopoietic precursor cell survive, self-renewal, proliferation and differentiation are regulated by specific glycoproteins called hematopoietic growth factors, or cytokines. • Most growth factors produced by bone marrow stromal cells in the hematopoietic microenvironment with exception of erythropoietin (EPO) that is produced mainly in the kidney. • Cytokines must be bound to surface receptors on their target cells to express their activity. 16-Jan-23 LECTURE 2 14 16 January 2023 HEMATOLOGY 16-Jan-23 LECTURE 2 15 Major Haemopoietic Growth Factors and Their Action Growth factor Mediates acute phase responses, cofactor for other growth factors. Interleukin 2 Growth factor for activated T-lymphocytes. Interleukin 3 Supports early haematopoiesis by promoting growth of stem cells. Stem cell factor GM-CSF 16-Jan-23 Actions Interleukin 1 Interacts with other factors to stimulate pluripotent stem cells. Growth factor promoting production of neutrophils, monocytes, macrophages, eosinophil, red cells, and megakaryocytes. G-CSF Lineage specific growth factor promoting production of neutrophils. M-CSF Lineage specific growth factor promoting monocyte and macrophage production. Erythropoietin Lineage specific growth factor promoting red cell production. Thrombopoietin Lineage specific growth factor promoting platelet production. LECTURE 2 16 16 January 2023 HEMATOLOGY Hematopoietic microenvironment: • It`s localized microenvironment in the hematopoietic organs that is crucial for the development of hematopoietic cells . • The HM includes cellular elements and extracellular components . • The HM provides homing and adhesive interactions important for hematopoietic cells and growth regulatory proteins within the marrow cavity. 16-Jan-23 LECTURE 2 17 16-Jan-23 LECTURE 2 18 16 January 2023 HEMATOLOGY Stromal cells: • They include adipocyte, endothelial cells , fibroblasts, T- lymphocyte, macrophage. • They are important source of cytokine production. • They produce the various components constituting the extracellular matrix of HM. 16-Jan-23 LECTURE 2 19 Extracellular matrix: • Produced and secreted by the stromal cells. • its composed of collagen, glycoprotein, glycosaminoglycan. • Collagen provide the structural support for the other component. • Glycosaminoglycan play a role in cell-cell interaction, mediate progenitor cells binding to stroma. 16-Jan-23 LECTURE 2 20