Lecture 2-Structure of RBCs erythropoeisis 2024.pdf

L2 Structure of RBCs and erythropoiesis ILOs By the end of this lecture, students will be able to 1. Recognize structural adaptation of erythrocytes to their function. 2. Interpret morphological changes of RBC’ s in different clinical conditions in the background of its structure and adaptation 3. I...

L2 Structure of RBCs and erythropoiesis ILOs By the end of this lecture, students will be able to 1. Recognize structural adaptation of erythrocytes to their function. 2. Interpret morphological changes of RBC’ s in different clinical conditions in the background of its structure and adaptation 3. Interpret blood film changes in different clinical conditions considering the stages of erythropoiesis. Erythrocytes Erythrocytes are non- nucleated blood elements that contain haemoglobin and some enzymes. Function: responsible for the transport of oxygen and carbon dioxide to and from the tissues of the body. Members of both sexes living at higher altitudes have correspondingly more red blood cells than residents living at lower altitudes. (WHY?) Human erythrocytes have an average life span of 120 days; when they reach that age, they display on their surface a group of oligosaccharides. Red blood cells bearing these sugar groups are destroyed by macrophages of the spleen, bone marrow, and liver. Structural adaptation of erythrocytes to their function: Shape; biconcave discs-like. This shape provides the cell with a large surface area relative to its volume, thus enhancing its capability for gaseous exchange. (Fig. 1) During stages of erythrocytes development in the bone marrow, they expel all cell organelles and the nucleus to provide more space for haemoglobin (WHY?). Red blood cells are packed with haemoglobin which is concentrated at the periphery of the erythrocyte to facilitate gaseous exchange. Figure 1. Shape of erythrocytes Page 1 of 5 Cell membrane of the erythrocyte 1. Role in flexibility: Its molecular structure provides the erythrocytes with a high degree of flexibility, thus can tolerate shearing forces (compression to pass through tiny blood capillaries) with maintaining structural and functional integrity. Figure 2. Cell membrane & cytoskeleton Molecular structure (Fig. 2) A network of cytoskeleton (mainly spectrin tetramers, actin & adducin) is attached to the cytoplasmic aspect of the red blood cell plasmalemma through anchoring peripheral proteins such as ankyrin and other transmembrane proteins. This cytoskeleton network helps to maintain the biconcave disk shape of the erythrocyte. Clinical hint Defects in the cytoskeletal components of erythrocytes result in various conditions marked by abnormally shaped cells. Hereditary spherocytosis, for instance, is caused by synthesis of an abnormal spectrin. Red blood cells of patients with this condition are more fragile and transport less oxygen compared with normal erythrocytes. Moreover, these spherocytes are preferentially destroyed in the spleen, leading to anaemia. (Figure 3) Figure 3 Page 2 of 5 2. Role of cell membrane in ions transport and blood grouping Ion channels (calcium-dependent potassium channels and Na+-K+ adenosine triphosphatase) which transports Cl-and HCO3. (Figure 4) Transmembrane glycoproteins, principally glycophorin A (responsible for MNS blood groups), and Rh factor Blood groups (ABO system) The extracellular surface of the red blood cell plasmalemma has specific inherited carbohydrate chains that act as antigens and determine the blood group of an individual for the purposes of blood transfusion. (Figure 4) Figure 4 Blood grouping systems Ions Channels Hemopoieses Postnatal hemopoiesis occurs in the bone marrow. Daily, more than 1011 blood cells are produced in the marrow to replace cells that leave the bloodstream, die, or are destroyed. During hemopoiesis, stem cells undergo multiple cell divisions and differentiate through several intermediate stages, eventually giving rise to the mature blood cells. The entire process is regulated by various growth factors and cytokines that act at different steps to control the type of cells formed and their rate of formation. All blood cells arise from pluripotential hemopoietic stem cells (PHSCs), which account for about 0.1% of the nucleated cell population of bone marrow. They are usually amitotic but may undergo bursts of cell division, giving rise to more PHSCs as well as to two types of multipotential hemopoietic stem cells (MHSCs): colony-forming unit-lymphocyte (CFU-Ly) cells and colony-forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte (CFU-GEMM) cells. Page 3 of 5 These two populations of MHSCs are responsible for the formation of various progenitor cells. Stem cells are commonly in the G0 stage of the cell cycle but can be driven into the G1 stage by various growth factors and cytokines. Progenitor cells also resemble small lymphocytes but are unipotential (i.e., committed to forming a single cell line, such as eosinophils). Their mitotic activity and differentiation are controlled by specific hemopoietic factors. Erythropoiesis Erythropoiesis, the formation of red blood cells, is under the control of several cytokines, namely steel factor, IL-3, IL-9, GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor), and erythropoietin hormone. The target is synthesis of maximum amount of Hb, then providing space to contain Hb by expelling the nucleus and organelles. Correlation of structural changes in each stage to Hb synthesis The maturation steps show decrease in the size of the cell and its nucleus. The cells can divide by mitosis till the stage of polychromatophilic erythroblasts where Hb synthesis starts. 1. The progenitor cell is CFU-E. 2. Proerythroblast; The first precursor cell. 3. Basophilic erythroblast; abundant ribosomes for Hb synthesis. 4. Polychromatophilic erythroblasts; Hb synthesis occurs resulting in basophilia together with eosinophilia of the cytoplasm due to formed Hb in cytoplasm. 5. Orthochromatophilic erythroblast; ribosomes begin to decrease, and the nucleus becomes eccentric to be expelled. 6. The prefinal stage; reticulocyte is non-nucleated spherical cell with remnants of ribosomes. It is released into the peripheral circulation. 7. Mature erythrocytes. Page 4 of 5 Figure 5. Maturation steps of erythrocytes Clinical hint Normal percentage of reticulocytes in blood is 0.5-2.5%. Abnormally increased percentage of reticulocytes indicates increased rate of erythropoiesis in conditions as hemorrhage or anemia, where rate of RBCs destruction exceeds rate of formation. Page 5 of 5