Hemopoiesis PDF

Hemopoiesis Dr. Sahar Khalil Prof. of Histology Agenda 1. Definition of hemopoiesis and hematopoietic tissues. 2. Describe the LM structure of bone marrow including all its components, 3. Differentiate between the LM structure of the two types of bone marrow: (yellow bon...

Hemopoiesis Dr. Sahar Khalil Prof. of Histology Agenda 1. Definition of hemopoiesis and hematopoietic tissues. 2. Describe the LM structure of bone marrow including all its components, 3. Differentiate between the LM structure of the two types of bone marrow: (yellow bone marrow and red bone marrow), 4. Relate the structure of the bone marrow to its function. 5. Describe & draw the stages of development of blood cells including erythropoiesis 2 Hemopoiesis Hemopoiesis means: the production of all blood cells Erythropoiesis: erythrocytes (RBCs) Leukopoiesis: leukocytes (WBCs) Thrombopoiesis: thrombocytes (platelets) Hemopoietic tissues: the sites where new blood cells are formed. It includes: 1)The yolk sac (Yolk sac phase) 2)Liver (hepatic phase) 3)Bone marrow (bone marrow phase) 3  Hemopoietic tissues 1) Yolk sac phase: Begins in the 2nd week of gestation, the yolk sac is the main site of hematopoiesis. Characterized by the formation of “blood islands” in the wall of the yolk sac of the embryo. 2) Hepatic phase: Starts from 8 weeks until 6 – 7 months of fetal life. Hemopoietic centers appear in the liver. Blood cell formation in these sites is largely limited to erythroid cells, although some leukopoiesis occurs in the liver. The liver is the major blood forming organ in the fetus during the second trimester. 4  Hemopoietic tissues 3) Bone marrow (myeloid) phase: BM (in cavities of all bones) becomes the main site of hemopoiesis from the 2nd trimester of fetal life. Also, other lymphatic tissues share with BM. After birth, hemopoiesis takes place only in the red bone marrow and lymphatic tissues as in the adult. But gradually recedes with time so that in normal adult life (20 years old), hematopoiesis is found mainly in flat bones (sternum, pelvis, vertebrae, ribs and proximal ends of long femur). 5 Agenda 1. Definition of hemopoiesis and hematopoietic tissue. 2. Describe the LM structure of bone marrow including all its components, 3. Differentiate between the LM structure of the two types of bone marrow: (yellow bone marrow and red bone marrow), 4. Relate the structure of the bone marrow to its function. 5. Describe & draw the stages of development of blood cells including erythropoiesis 6  Bone Marrow: Bone marrow (BM) is the major location for hematopoiesis. In adults, active BM is a jelly-like substance lies entirely within the spaces of bone, in the medullary cavity of young long bones and the spaces of spongy bone. There are two types of marrow found in the body: (1) The highly vascular red marrow which is haematopoietically active, (2) The fat rich yellow marrow that is filled with adipocytes and essentially excludes hemopoietic cells. 7  Bone Marrow: Stroma loose reticular C.T. Parenchyma * Hemopoietic cords (islands of cells), * Sinusoids. 8  Bone Marrow: C.T. stroma: ✓ Modified fibroblasts (adventitial reticular cells): * Branched * Produce reticular fibers to support hematopoietic cells. * Many cellular adhesion molecules on surfaces of reticular cells. ✓ Reticular fibers supporting hemopoietic cells and macrophages. 9  Bone Marrow: Parenchyma: ✓ Sinusoids: * Thin-walled vessels (15-100 µm). * Form an extensive, communicating network. * Sinusoidal wall consists of fenestrated endothelial cells, a discontinuous basal lamina & an outer adventitial cell layer. ✓ Hemopoietic cords (islands of cells): * Contain megakaryocytes, developing blood cells, macrophages, mast cells & some adipose cells. * Hemopoietic cords are well organized: - Erythrocyte nests contains a macrophage & found near the sinusoidal wall. - Megakaryocytes located adjacent to sinusoidal wall. - Granulocyte nests located farther from the sinusoidal wall. 10  Bone Marrow: Megakaryocyte: giant cells, up to 150 μm in diameter, with ✓ Nucleus: a large, ovoid or kidney shaped, polyploidy (endomitosis), irregularly lobulated with coarse chromatin. ✓ Cytoplasm: Basophilic, contains numerous mitochondria, a well-developed rER, and an extensive Golgi apparatus from which arise the conspicuous specific granules of platelets. ✓ Typically, found near sinusoidal capillaries. ✓ Function: produce platelets Megakaryocyte 11 Agenda 1. Definition of hemopoiesis and hematopoietic tissue. 2. Describe the LM structure of bone marrow including all its components, 3. Differentiate between the LM structure of the two types of bone marrow: (yellow bone marrow and red bone marrow), 4. Relate the structure of the bone marrow to its function. 5. Describe & draw the stages of development of blood cells including erythropoiesis 12  Types of Bone Marrow: Red Bone Marrow Yellow Bone Marrow Color red due to its high yellow due to its high content of HB (in RBCs) content of fat cells Site In fetus: most of the Most of marrow in adults marrow In adults: present in epiphyses of long bones, vertebrae, sternum & ribs. Function - Production of blood - Storage of fats, cells, - In time of need, it can - Destruction of old RBCs. change into active red type. 13 Red Bone Marrow Yellow Bone Marrow 14 Agenda 1. Definition of hemopoiesis and hematopoietic tissue. 2. Describe the LM structure of bone marrow including all its components, 3. Differentiate between the LM structure of the two types of bone marrow: (yellow bone marrow and red bone marrow), 4. Relate the structure of the bone marrow to its function. 5. Describe & draw the stages of development of blood cells including erythropoiesis 15  Function of Bone Marrow: * Production of the blood cells: - RBCs, granulocytes, monocytes & platelets released into circulation. - Lymphocytes require additional maturing. * Destruction of old RBCs by sinusoidal macrophages. * Differentiation of B-lymphocytes. * Storage of iron (breakdown of Hb) in sinusoidal macrophages. 16 Agenda 1. Definition of hemopoiesis and hematopoietic tissue. 2. Describe the LM structure of bone marrow including all its components, 3. Differentiate between the LM structure of the two types of bone marrow: (yellow bone marrow and red bone marrow), 4. Relate the structure of the bone marrow to its function. 5. Describe & draw the stages of development of blood cells including erythropoiesis 17  Developing blood cells: ❑ Hemopoietic Stem Cells: All blood cells arise from a pluripotential hemopoietic stem cell (PPSC) in the bone marrow. - Similar to large lymphocytes. - PPSCs are rare (0.1%), having low mitotic activity: - Self renewal, - Multiple colony-forming stem cells (CFU): a) CFU-M (multipotential myeloid stem cells) [include granulocytes, monocytes, erythrocytes, and megakaryocytes] b) CFU-L (multipotential lymphoid stem cells) - Identification: surface marker (CD34+, p170 pump & c-kit) Homebox genes: early stages Erythrocytes: Hox2 Myeloid: Hox1 18  pluripotential hemopoietic stem cell (PPSC) colony-forming stem cells – myeloid colony-forming stem cells – lymphoid (CFU-M) (CFU-L) 10/14/2023 PRESENTATION TITLE 19  Developing blood cells: ❑ Progenitor Cells: Committed to single cell lineage CFU. - Similar to large lymphocytes. - divide more rapidly with self-renewal. - There are four major types of progenitor cells/CFUs: Erythroid lineage of erythrocytes Thrombocytic lineage of megakaryocytes for platelet formation Granulocyte-monocyte lineage of all three granulocytes and monocytes Lymphoid lineage of B lymphocytes, T lymphocytes, and natural killer cells. ❑ Precursor Cells (blasts): Arise from progenitor cells. - No self-renewal - Gradually assume the morphologic characteristics of its mature type 20 10/14/2023 PRESENTATION TITLE 21 Major changes in developing hemopoietic cells 22  Hemopoietic stimulating factor: ❑ Stem cell factor (SCF) (Steel factor): Mitogen for all hemopoietic progenitor cells. Secreted by stromal cells of bone marrow. ❑ Erythropoietin (EPO): Mitogen for all erythroid progenitor and precursor cells. Secreted by the kidney & hepatocytes. ❑ IL-3 & IL-4 23  Erythropoiesis: ❑ Erythrocytes develop from CFU-M. ❑ The erythropoietin- sensitive erythrocyte progenitor cells (CFU-E) gives rise to the first recognizable erythrocyte precursor, the “proerythroblast”. 24  Proerythroblast: Size:12-15 µm in diameter. Cytoplasm: mildly basophilic (due to ribosomes & polysomes). Nucleus: large, spherical with 1-2 nucleoli. 25  Basophilic erythroblast: Size:14 µm in diameter (smaller). Cytoplasm: deeply basophilic (due to ribosomes & polysomes). Nucleus: smaller, more heterochromatic nucleus. No nucleoli seen. 26  Polychromatophilic erythroblast: Last cell capable of mitosis. Hemoglobin production begins. Size:11 µm in diameter (smaller). Cytoplasm: polychromatophilic (blue & red color). Nucleus: small & deeply stained. 27 Orthochromatophilic erythroblast (Normoblast): Size: 8 µm in diameter (smaller). Cytoplasm: acidophilic (due to Hb). Nucleus: small, deeply stained (pyknotic). found near the cell membrane. extruded nucleus is phagocytosed by macrophages. 28 Polychromatophilic erythrocyte (Reticulocytes): Immature RBCs. Size: slightly larger than RBCs. Cytoplasm: still retains some polyribosomes (spots/threads) [reticulum]. Nucleus: extruded. ˂1.5% of the total erythrocytes. Demonstrated by supravital stain (Brilliant cresyl blue). 29 Erythrocytes: Mature RBCs & biconcave discs. Size: 7.5 µm. Cytoplasm: full of Hb (acidophilic). Nucleus: No. Life span: 120 days. Duration of erythropoiesis: PPSC to RBC: 21 days. Maturation phase from reticulocyte to mature RBC: 2 days 30 31 Thank you