Lecture 1 Hematopoiesis Prof Wadie M 2024 PDF

The course intended learning outcomes (CILOs) :By the end of the hematopathology course, the learner should be able to Hematopathology Course...

The course intended learning outcomes (CILOs) :By the end of the hematopathology course, the learner should be able to Hematopathology Course Demonstrate knowledge related to normal.hematopoiesis.1 Identify common hematological problems related to.2 disorders of erythrocytes (RBCs), leucocytes.(WBCs), platelets and bleeding Interpret physical findings, laboratory tests and.3 diagnostic procedures of common hematological Prof. Wadie Elmadhoun.problems to reach the provisional diagnosis 2024 Course outlines The intended learning outcomes Hematopoiesis.1 By the end of the lecture, the learner should be Red Cell Disorders.2 Lecture 1: Normal Blood Cells synthesis :able to White Cell Disorders.3 (Hematopoiesis).Define hematopoiesis.1 Bleeding Disorders.4.Describe the bone marrow micro-environment.2 Complications of Blood Transfusion.5 Describe the morphology and identify the.3 Disorders of the spleen and thymus.6.names of hematopoietic cell series Identify the role of hematopoietic growth.4.factors Haematopoiesis. It is the process of formation of blood cells Blood: is a suspension of non dividing end stage cells :which include.red blood cell (RBC): oxygen delivery to the tissue.1.Platelets : hemostasis.2. WBC : host defense mechanisms.3  Haematopoiesis : Sites of hemopoiesis The turnover of differentiated hemopoietic cells in adult weighing70 Kg is over 0.5 trillion cells During prenatal development, the sites of per day including 200 billion RBCs and 70 billion.hematopoiesis change several times.neutrophils The inner cell mass of the blastocyst contains :The normal life span of ;cells that are pluri-potent RBC is 120 days.1 that develop into each of the three embryonic PMN is 6-8 hours.2 germ cell layers (mesoderm, endoderm, and Platelet is 7-10 days.3.ectoderm).Lymphocytes may survive for many years.4 : Sites of hemopoiesis : Sites of hemopoiesis At about 21 days of gestation the mesoderm gives rise to basophilic cells known as blood island which is localized in the yolk sac and it represents the primitive hemopoiesis. (predominantly.erythroblasts) : Sites of hemopoiesis : Sites of hemopoiesis : Sites of hemopoiesis At (day 28-40) these cells will migrate to the At about 6 weeks (42 days) hematopoiesis After 10–12 weeks, haemopoietic stem cells start to* migrate to the bone marrow and hematopoiesis starts in aorta-gonad-mesonephros region (AGM) starts in the liver, with granulopoiesis and the bone marrow at about 20 weeks, and it becomes the. forming definitive hemopoiesis.megakaryopoiesis major site of hematopoiesis after the 24th week of These cells are common precursors of It continues until about 5 months of gestation.gestation and continues throughout life endothelial and haemopoietic cells. where the bone marrow (BM) takes over Hemopoiesis appears also in the spleen and to lesser*.extend in the lymph nodes at about mid fetal life (haemangioblasts) and they seed to the liver, At about 60 days definitive erythroid cells are released*.spleen and bone marrow. into the circulation  Bone marrow At birth, the marrow in all bones of the body appears red and. contains no fat at puberty the hemopoietic marrow is limited to the central :skeleton , thorax ( ribs , clavicle , scapula and sternum ).1 , vertebrae.2 , skull.3 pelvic bone.4.and upper ends of the long bones.5 Bone marrow micro-environment is important for :The characteristics Hemopoietic stem cells (HSC) hematopoiesis The haemopoietic stem cells are rare, perhaps 1 in every 20.1.million nucleated cells in bone marrow. They have the appearance of a small or medium-sized lymphocyte.2 They are positive for: CD34+, CD133+, CD117+, and negative for:.3.-CD38-, CD3-, CD19 Self-renewal capacity which is essential to provide a continuous life.4. long supply of functional hematopoietic cells; (i.e.) Immortality HSCs are capable of differentiating into all mature hematopoietic cell.5 lineages ; multipotential stem cell, which gradually show limited capacity to self-renewal and much more restricted differentiation.options The first cells committed to lymphoid and myeloid lineages are.6 called common lymphoid progenitors (CLP) and common myeloid. progenitors (CMP) Stem cells (HSC) Stem cells (HSC) :These HSC have 4 possible fates After Hematopoietic stem cells undergo self- Self-renewal.1 replication, most descendants of the stem cells are Differentiation.2.committed to differentiate Migration.3 Apoptosis.4.This commitment process occurs through stages Normally, a large fraction of HSC are quiescent, in G0 phase, After lineage commitment, the progenitor cells mainly influenced by the cytokine transforming growth factor continue to differentiate and mature into the.β (TGF-β).terminally differentiated cells found in the blood HSC move outside bone marrow, a process known as.This process is controlled by specific cytokines mobilization or get back from circulation, a process known as.homing  : Erythropoiesis All the progenitor and adult red cells are termed the erythron The earliest characterized progenitor committed to the erythroid lineage is the burst forming unit–erythroid.(BFU-E); it can undergo many divisions (bursts) This progenitor requires ,interleukin-3 (IL-3).1 granulocyte-macrophage colony stimulating factor (GM-CSF).2 ,erythropoietin (EPO).3 and other factors for proliferation, prevention of apoptosis,.4. and differentiation Normal hematopoiesis RBCs development RBCs development As maturation progresses, a late progenitor will develop :which is colony forming unit–erythroid (CFU-E); then. Proerythroblast : This is the first erythroid precursor.1 Basophilic Erythroblasts.2 Polychromatophilic Erythroblasts.3 Orthochromic Erythroblasts.4 Reticulocyte.5 RBC.6 Normoblast, reticulocyte, RBC Reticulocytes  Erythropoietin Neutrophil and RBC Development Erythoblasts and normoblasts Normally, 90% of the hormone is produced in the peritubular interstitial cells of the kidney and 10% in the liver and.elsewhere There are no preformed stores and increased demands for EPO are met by an increase in the number of EPO-producing.cells rather than by an increased synthesis of EPO the stimulus to erythropoietin production is the low oxygen. (O2) tension in the tissues of the kidney : Myelopoiesis Myeloid series It starts from the CFU-GEMM, which is multilineage.Myeloblasts.1 progenitor that is committed to tri- (CFU-GMEo) then to Promyelocytes.2 bipotential progenitor (CFU-GM) and further differentiated to.unipotential progenitor ex Myelocytes.3 CFU-Eo; (Eosinophil) Metamyelocytes.4 CFU-G; (granulocyte) CFU-M; (monocyte/macrophage) Band cells.5 CFU-baso. (basophil).Mature: neutrophils, basophils, eosinophils.6 Hematopoietic growth factors Lymphoid cell develoment B lymphocytes development T lymphocyte development T and B lymphocyte development T cell Thanks