L2 RBCs Structure & Development PDF

Dr. Shehab Hafez Semester (3): Blood & Lymphatic System Module (BMS201) Histology of RBCs & Erythropoiesis Prof. Dr. Shehab Hafez Professor & Head of Histology Department Faculty of Medicine. Mansoura University...

Dr. Shehab Hafez Semester (3): Blood & Lymphatic System Module (BMS201) Histology of RBCs & Erythropoiesis Prof. Dr. Shehab Hafez Professor & Head of Histology Department Faculty of Medicine. Mansoura University 2024-2025  Dr. Shehab Hafez 1. To determine normal shape, number, size and structure of RBCs. 2. Correlate between structure and function of RBC. 3. To demonstrate knowledge of hemopoiesis, Its sites & Hemopoietic stem cells. 4. To determine steps of erythropoiesis.  Dr. Shehab Hafez Blood is a specialized connective tissue in which cells (RBCs, WBCs) are suspended in a fluid extracellular material called plasma. Also it contains fibers (fibrin) that forms blood clot). Contents of blood Formed elements Blood plasma (Blood cells) 1. RBCs (Erythrocytes). 2. WBCs (Leucocytes). 3. Blood platelets (Thrombocytes).  Dr. Shehab Hafez Preparing a blood smear ▪ Blood cells can be studied histologically in smears prepared by spreading a drop of blood on a microscope slide. Staining 1. Neutral stains: example: Leishman’s stain: a mixture of acidic (eosin) & basic (methylene blue) dyes. 2. Romanowsky stains: polychromatic stains: examples: Giemsa and Wright stains  Dr. Shehab Hafez RBCs (Erythrocytes) Normal shape of RBCs ▪ In stained blood smear: RBCs are Biconcave discs. With a pale center. ▪ This shape provides a 20% to 30% greater surface area & facilitates gas exchange. With scanning EM (SEM) biconcave discs are better seen. With Transmission EM (TEM) RBCs inside a capillary have a classic dumbbell shape (DB).  Dr. Shehab Hafez Abnormal shape of RBCs 1.Spherocytosis (biconvex) The center of RBC appears dark. 2.Crenation Shrinkage and notching of RBC when exposed to hypertonic solution. 3. Swelling & rupture When exposed to hypotonic solution. Marked hypotonic solution may cause rupture of the cell membrane and hemolysis. Only remnants of RBCs (cell ghosts) appear.  Dr. Shehab Hafez Abnormal shape of RBCs In Sickle cell anaemia Inherited disease (Sickle cell disease) The RBCS appear either: The sickled RBC is less flexible and Sickle-shape. more fragile and has a short life Teardrop-shape. span → anemia. It increases blood viscosity promoting blood coagulation.  Dr. Shehab Hafez Size (diameter) of RBCs ▪ Normal diameter: 6-9 µm (average 7.5 µm). ▪ In macrocytic anemia: RBC size˃ 9 µm. ▪ In microcytic anemia: RBC size ˂ 6 µm. ▪ Thickness: 2.6 μm thick at the rim, but only 0.75 μm thick in the center (→ biconcave shape). Normal concentration of RBCs in blood ▪ In males: 4.1- 6.0 million/ µL (microliter) or mm³ ▪ In females: 3.9- 5.5 million/ µL (microliter) or mm³  Dr. Shehab Hafez Structure of RBCs The erythrocyte is highly adapted for its principal function of oxygen and carbon dioxide transport How? 1. Highly flexible cell membrane with a supporting cytoskeleton ▪ The cell membrane of RBC is formed of: 40% phospholipids in the form of a bilayer, 10% carbohydrates, and 50% protein. ▪ Cytoskeleton: A network of proteins (spectrin, ankyrin and actin) supports the cell membrane & provides a great degree of flexibility of RBC This flexibility → Easy change in shape of RBCs→ easy passage through small capillaries.  Dr. Shehab Hafez 2. No nucleus…No cell organelles. 3. The RBC are filled with: ▪ Haemoglobin molecules. ▪ Enzymes of anaerobic glycolysis (source of energy), as the RBC has no mitochondria. Life span of RBCs ▪ 120 days. ▪ Dead or worn-out RBCs are removed from the circulation by macrophages of the spleen, liver, and bone marrow. Splenic macrophages phagocytosing dead RBCs  Dr. Shehab Hafez Hemopoiesis  Dr. Shehab Hafez Hemopoiesis Definition: blood cells have a limited life span. They are continuously replaced by differentiation and maturation of stem cells in the hematopoietic organs. Sites of hemopoiesis Age Site Fetus: 0-2 months Yolk sac 2-5 months Liver, spleen 5-9 months Bone marrow Infants Bone marrow, particularly all bones. Adults Bone marrow in: Vertebrae, ribs, sternum, sacrum, pelvic bones, proximal ends of femur. All blood cells are derived from Pluripotential Hemopoietic stem cell (HSC)  Dr. Shehab Hafez Pluripotential Hemopoietic stem cell (HSC) Active proliferation to Proliferate and differentiate to produce more maintain their own mature and differentiated cells called: population (self-renewing). Progenitors ▪ Definition of Progenitor cells: they are committed to produce specific blood cells. ▪ Types of progenitor cells: Myeloid stem cell Lymphoid stem cell  Dr. Shehab Hafez Pluripotential Hemopoietic stem cell (HSC) Myeloid stem cell Lymphoid stem cell ▪ Colony forming unit Granulocytes-monocytes ▪ Colony forming unit (CFU-GM): Lymphocytes (CFU-L): 1. Neutrophils. 1. B- lymphocytes. 2. Eosinophils. Granulocytes 2. T-lymphocytes. 3. Basophils. 3. Natural killer cells. 4. Monocytes. ▪ Colony forming unit Erythrocytes (CFU-E). ▪ CFU Megakaryocytes (CFU-Meg)→ platelets. HSC → Progenitor cell →CFU →Precursor (blast) cells for each type of blood cells.  Dr. Shehab Hafez Hematopoietic stem cell (HSC) Progenitor cells (myeloid or Lymphoid stem cells) Colony forming unit cells (CFU) Precursor (blast) cells Mature cells  Dr. Shehab Hafez Hemopoiesis  Dr. Shehab Hafez Erythropoiesis Hematopoietic stem cell (HSC) The first precursor (blast cell) of RBCs is Proerythroblast Progenitor cells (myeloid stem cells) Colony forming unit cells (CFU erythrocytes) Precursor (blast) cells Mature erythrocyte (Proerythroblasts) Proerythroblast Erythrocytes (RBCs)  Dr. Shehab Hafez Erythropoiesis Size Nucleus Cytoplasm Proerythroblast Active Basophilic Basophilic Erythroblast Less active Basophilic (early normoblast) Polychromatophilic Condensed Basophilia and acidophilia erythroblast (intermediate Gradual normoblast) reduction in Orthochromatophilic size More condensed Acidophilic and little Erythroblast (late normoblast) and eccentric basophilia Reticulocyte Extruded (No Acidophilic with a reticulum nucleus) of ribosomal RNA Mature erythrocyte No nucleus Acidophilic with a pale center  Dr. Shehab Hafez Erythropoiesis Proerythroblast Orthochromatophilic Reticulocyte erythroblast Basophilic Polychromatophilic Mature erythrocyte erythroblast erythroblast  Dr. Shehab Hafez ▪ 1% of total RBCs in the peripheral blood. Reticulocytes ▪ Have mitochondria and a reticulum of ribosomal RNA in the center. ▪ When severe erythrocyte loss occurs, such as after haemorrhage or haemolysis, the rate of erythrocyte Reticulocytosis production in the bone marrow increases and the proportion of reticulocytes in circulating blood rises  Dr. Shehab Hafez Resources ▪ Junqueira LC, Carneiro J: Junqueira’s Basic Histology. Text and Atlas, thirteenth edition (2013), LANGE Mc Graw Hill. ▪ Gartner LP and Hiatt JL: Color Textbook of Histology. Third edition (2007). Saunders Elsevier. Prof. Dr. Shehab Hafez