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23 January 2023 LECTURE 3 23/01/2023 Erythrocyte 1 • It means formation of Red blood Cells. • The life cycle of erythrocyte include stimulation of lineage commitment and maturation of precursor cells in the bone marrow by erythropoietin and the other cytokines. • A circulating life span for mat...

23 January 2023 LECTURE 3 23/01/2023 Erythrocyte 1 • It means formation of Red blood Cells. • The life cycle of erythrocyte include stimulation of lineage commitment and maturation of precursor cells in the bone marrow by erythropoietin and the other cytokines. • A circulating life span for mature cells is approximately 120 ± 10 days. • The destruction of senescent cells by mononuclear cells in the spleen, liver and bone marrow. 23/01/2023 Erythrocyte 2 23 January 2023 LECTURE 3 Erythroid progenitor cells: • Red cell production begins with the hematopoietic stem cell (HSC). • Stem cell differentiation is induced by cytokines in specialized microenvironment to produce a committed erythroid progenitor cell. • The committed ( unipotential) progenitor cell compartment consists of two populations : burst-forming unit-erythroid(BFU-E) and colonyforming unit-erythroid(CFU-E). 23/01/2023 Erythrocyte 3 23/01/2023 Erythrocyte 4 23 January 2023 LECTURE 3 Erythroid maturing cells: • Nucleated erythrocyte precursors in the bone marrow called erythroblast. The process of erythroid maturing cells formation include six morphologically defined stages :- 1 2 Basophilic Normoblast Pronormoblast 4 5 Orthochromatic Normoblast 23/01/2023 3 Polychromatic Normoblast 6 Reticulocyte Erythrocyte Erythrocyte 5 Erythroid maturing cells: • The normoblasts spend from 5 to 7 days in the proliferating and maturing compartment of the bone marrow. • After reaching the reticulocyte stage, there is an additional 2-3 days of maturation, the first 1-2 days of which are spent in the bone marrow befor is released to the peripheral blood. 23/01/2023 Erythrocyte 6 23 January 2023 LECTURE 3 5 - 7 day 23/01/2023 Erythrocyte 7 stages of erythrocyte maturation 23/01/2023 Erythrocyte 8 23 January 2023 LECTURE 3 the cell mature: 1- decrease in size. 2- expulsion of nucleus. 3- increased in hemoglobin production( pink or salmon color) 23/01/2023 Erythrocyte Reticulocytes 0.5 – 2.5% 9  Immature RBCs.  NO nuclues contain residual ribosomal RNA.  Stage before mature RBC  It remain in bone marrow for 1-2 days , then for other 2 days in circulation .. Mature RBC .  % 0.5 -2.5 , increase in hemolysis , bleeding due to Rapid RBC production 23/01/2023 Erythrocyte 10 23 January 2023 LECTURE 3 Erythrocytes / RBC • Shape : Flat Biconcave Disc , • Non-nucleated • Diameter 7-8 µm • Average volume 80 -100 fl • Flexible • Number = 4.8 million in female = 5.5 million in male • Life span : 120 day 23/01/2023 Erythrocyte 11 • Erythropoietin (EPO) is the only cytokine important in regulating the final stages of erythroid maturation( the maturing cells) • Androgen appear to both stimulate EPO secretion and directly after the erythropoietin • activity (explains the difference of hemoglobin according to age and sex). 23/01/2023 Erythrocyte 12 23 January 2023 LECTURE 3 Erythropoiesis O2 O2 • Erythropoietin: Hormone produced by kidney , stimulate RBC production 23/01/2023 Erythrocyte 19-13 Factors affecting Erythropoiesis 1- Hypoxia Erythropoiesis is stimulated by Erythropoietin hormone produced by the kidney in response to hypoxia (low oxygen in the blood) • Hypoxia caused by: • Low RBC count (Anemia) • Hemorrhage • High altitude , Exercise …( physiological ) • Prolong heart failure • Lung disease ( these factors increase levels of erythropoietin ) 23/01/2023 Erythrocyte 14 23 January 2023 LECTURE 3 2- Healthy kidney : it’s the site of Erythropoitin secretion , 90% 23/01/2023 Erythrocyte 15 3- Healthy liver • production of 10% erythropoietin & globin part of Hb • it is a source for iron, copper & vit B12 (all are important for erythropoiesis) 4- Hormones : • Erythropoietin ( major stimulus ) , testosterone , thyroxin ,growth hormones& cortisol . 23/01/2023 Erythrocyte 16 23 January 2023 LECTURE 3 5- Healthy diet : • Vit B12. folic acid (important for maturation of RBC ) • Iron (essential for formation of heme part of Hb )& Copper (acts as catalyst for Hb synthesis ) • Protein of high biological value (essential for globin synthesis) 6. Healthy bone marrow : It’s a site of RBC formation , ( Bone marrow disease ) 23/01/2023 Erythrocyte 17 Red Cell Membrane: • Mature erythrocyte lack the intracellular organelles( nucleus, ribosome, mitochondria) and enzymes necessary to synthesize new lipid and protein. • Thus extensive damage to the membrane can't be repaired and excluded from circulation by the spleen. 23/01/2023 Erythrocyte 18 23 January 2023 LECTURE 3 Red cell membrane 23/01/2023 Erythrocyte 19 Erythrocyte Membrane: • The erythrocyte membrane is a phospholipid bilayer-protein complex composed of 52% protein, 40% lipid and 8% carbohydrate. • 1-lipid composition: • Approximately 95% of the lipid content of the membrane consists of equal amounts of unesterified cholesterol and phospholipids 23/01/2023 Erythrocyte 20 23 January 2023 LECTURE 3 Erythrocyte membrane: • The remaining lipids are free fatty acid( FA) and glycolipids. Mature erythrocyte are unable to synthesize fatty acid, phospholipid, or cholestrole. They depend on lipid exchange with the plasma and fatty acid acylation for phospholipid repair and renewal during their 120 day life span. A small part of membrane lipid consist of glycolipid which is responsible for antigenic properties( carry red cell blood group). 23/01/2023 Erythrocyte 21 Erythrocyte membrane: • The erythrocyte membrane are of two types: integral and peripheral . • Both types of membrane proteins are synthesized during erythroblast development. • A- Integral Protein: • Include transport proteins and glycophorins. • The three major glycophorins (A,B,C) responsible blood group antigens. 23/01/2023 Erythrocyte 22 23 January 2023 LECTURE 3 Erythrocyte membrane: • They play role in attaching the skeletal protein to lipid bilayer. • Band 3 ( anion exchange protein): it’s the major integral protein , is the transport channel for chloride-bicarbonate exchange, which occur during the transport of Co2 from the tissue back to the lung. • Its major binding site for glycolytic enzymes. • Responsible for blood group antigens. 23/01/2023 Erythrocyte 23 Erythrocyte membrane: • B- peripheral proteins: • It include two major proteins: spectrin and ankyrin • Its serve as skeletal support for the membrane lipid bilayer. • This skeletal proteins give the red cell membrane their viscoelastic properties and contribute to the cell shape, deformability and membrane stability. 23/01/2023 Erythrocyte 24 23 January 2023 LECTURE 3 Erythrocyte membrane: • B- peripheral proteins: Deformability of the red cell is due to: 1-its biconcave shape( large surface area to volume ratio) 2-the viscosity of hemoglobin • 3-the viscoelastic properties of erythrocyte membrane. 23/01/2023 Erythrocyte 25 Function of RBC membrane 1. Shape – maintain erythrocytes biconcave shape which Provides the optimum surface area for respiratory gases exchange 2. Provide deformability, elasticity , through a special protein in cytoskeleton , to change their shape , size , squeeze to pass through capillaries 3. Provides permeability : Allows water and electrolytes to exchange , to maintain high level of intracellular K⁺ , and low Ca ⁺ , Na ⁺ 4. The membrane of RBC contains blood group antigen 23/01/2023 Erythrocyte 26