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Erythropoiesis .
Medicine (A100)
Queen Mary University of London
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2 – Erythropoiesis: The formation and life cycle of Red Blood Cells Red Blood Cell Formation Before birth o Mesoblastic stage (week 3) – nucleated red blood cells form in the yolk sac and mesothelial layers of the placenta o Hepatic stage (week 6) – erythropoiesis mainly in the liver and spleen o Myeloid stage (3rd month onwards) – bone marrow gradually becomes the principal source of red blood cells After birth o Up to 5 years – bone marrow in all bones o Age 5 to 20/25 years – marrow of long bones only o Over 25 years – red blood cells produced mainly in the marrow of membranous bones e. vertebrae, sternum, ribs, cranial bones, ilium Bone Marrow Also known as myeloid tissue Soft spongy material, often divided into red marrow and yellow marrow o Yellow – fat droplets and cells o Red marrow – most erythropoiesis occurs Erythropoiesis Starts with the haematopoietic stem cell (haemocytoblast) in the marrow Differentiates into common myeloid progenitor (proerythroblast) – a stem cell for production of blood cells Develops into an erythroblast o Then undergoes successive changes where its nucleus progressively shrinks and its cytoplasm becomes filled with haemoglobin o Haemoglobin causes the cytoplasm to turn clear The nucleus is expelled and becomes a reticulocyte o Some are released into the blood o Reticulocytes can mature into adult RBCs in the circulation Erythrocyte Round, biconcave disc shaped Smooth Diameter 7 um Stains with EOSIN (more stain at periphery) Can deform easily Volume of about 90 cu mm (1 cu µm = 1 femtolitre (fl)= 10-15 lt) Reticulocyte Some ribosomes or ribosomal RNA shown as dark markings About 1% of red blood cells are reticulocytes The Lymphoid Cell Family Some haemocytoblast stem cells form lymphoid progenitors These cells differentiate into the various types of lymphocytes Lymphocytes are generally regarded as part of the RBC Count Remains constant in a healthy adult Male – 5 ± 0 x 106 /µL Female – 4 ± 0 x 106 /µL 120 ± 30 Days life span (die due to oxidative damage) Control of Erythropoiesis Controlled by erythropoietin (EPO), a protein produced in fibroblast interstitial cells in the kidney around the proximal tube The kidney has a tightly regulated glomerular filtration rate, and a steady usage of oxygen (oxygen levels not altered by exercise or changes in blood pressure, determined by Hb in arterial blood) The EPO secreting cells are sensitive to hypoxia o If hypoxia occurs, it must be due to reduced carriage of oxygen o The hypoxia stimulates EPO release which acts on erythropoeitic stem cells to increase RBC production Hormonal Control of Erythropoiesis Effects of EPO o More rapid maturation of committed bone marrow cells o Increased circulating reticulocyte count in 1 – 2 days Testosterone also enhances EPO production, resulting in higher RBC counts in males EPO acts to stimulate maturation of erythroblasts in the red bone marrow Erythrocyte Sedimentation Rate (ESR) Erythrocytes have a negative surface charge due to membrane glycoproteins containing sialic acid o Ensures they electrostatically repel each other so do not stick together Inflammatory reactions or abnormal levels of certain proteins (e. fibrinogen) in the blood release molecules which bind to the RBC membrane and reduce the charge, enabling the red cells to stick together The cells clump to form stacks called ‘rouleaux’ which settle to the bottom of the test tube quicker This increases the ESR – raised ESR is a non-specific marker of infection in blood Energy Metabolism of RBCs RBCs do not have mitochondria so cannot use oxidative metabolism to make ATP o They require a small amount of ATP to power sodium pumps in the membrane (cell would burst without) o Also need ATP to power GLUT1 transporters which take up glucose They make ATP via anaerobic glycolysis and use the pentose phosphate pathway for NADPH The end product of the glycolytic pathway in erythrocytes is lactic acid After about 120 days RBCs are removed from the blood by macrophages as they pass through the spleen o Cells in the spleen detect worn out RBCs via surface antigens Formation & Destruction of RBCs
Erythropoiesis .
Module: Medicine (A100)
University: Queen Mary University of London
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