Lecture 3 - Physiology of RBCs, Anemia & Polycythemia PDF

Faculty of Medicine Academic Year: 2024/2025 Year: 1 Semester: 1 Module: Blood and body fluids (BLF-103)  PHYSIOLOGY OF RBCs, anemia and polycythemia By: Dr. Ramadan Saad Department: Physiology Module: BLF-...

Faculty of Medicine Academic Year: 2024/2025 Year: 1 Semester: 1 Module: Blood and body fluids (BLF-103)  PHYSIOLOGY OF RBCs, anemia and polycythemia By: Dr. Ramadan Saad Department: Physiology Module: BLF-103  Objectives o Define hematocrite value. o Describe the structural functional relation of RBCs o explain the control of erythropoiesis. o Differentiate between the role of iron and vitamin B12 in erythropoiesis. o List the basic characteristics of each type of anemia. o Define polycythemia and describe its causes. BLOOD: COMPOSITION 4 THE FORMED ELEMENT: CELLS BLOOD CELLS ERYTHROCYTES LEUCOCYTES THROMBOCYTES 5  RED BLOOD CELLS 6 Physical and Chemical Properties of the Red Cells Hematocrit Function Material for the production Erythropoiesis 7  Hematocrit ⮚ Concept: The percentage of blood volume occupied by the packed red blood cell volume ⮚ Normal range: man, 40% - 50%, Women 37% - 48% 8 9  Function: ⮚ To transport oxygen from the lungs to the tissue (function of hemoglobin) ⮚ To transport carbon dioxide in blood. The arterial and venous red cell 10 OXYGEN & CO2 TRANSPORT NOMAD:2005: BP: INTROVERVIEW 11  RED BLOOD CORPUSCLES (RBCs) ❑ RBCs constitute 99% of blood cells. ❑ They are biconcave discs (importance?), 2.2 micron in thickness and 7.2 micron in diameter. ❑ Their volume is 90 cubic micron. ❑ RBCs count is 5.4 million/mm3 in males and 4.8 million/mm3 in females. ❑ They have an elastic membrane (Why?). ❑ They contain hemoglobin, K+ and carbonic anhydrase enzyme. ❑ They have no mitochondria so they depend on anaerobic metabolism. 12  Hemoglobin ❑ Hb is the red- oxygen carrying pigment of RBCs. 2 ❑ The amount of Hb is: 1 3 15- 16 g/100 ml blood in males and 13-14 g/100 ml 4 blood in females. Globin protein consisting of 4 polypeptide chains One heme pigment attached to each polypeptide chain each heme contains an iron ion (Fe+2) that can combine reversibly with one oxygen molecule. Hb binds to CO2 to form carbamino compounds. It binds to the protein part. Function of carbonic anhydrase enzyme: (?)  HEMOGLOBIN: VARIETIES heme is the same varieties are due to changes in the peptides of the globin moiety. physiological varieties: 1. adult Hb: Hb A: 2 alpha and 2 beta polypeptide chains. preponderant form Hb A2: two alpha and two delta chains (α2δ2) : a minor component 14  Hb: PHYSIOLOGICAL VARIETIES 2. fetal hemoglobin: Fetal hemoglobin (Hb F; alpha2, gamma2) is the major hemoglobin in fetal red blood cells (RBCs) during gestation gamma chains have more affinity to oxygen. this helps the fetus to acquire oxygen from the mother. 15  SICKLE CELL DISEASE Hb S: Valine Is Substituted For Glutamic Acid At 6 Position Of Beta Chain. When Hb S Is Reduced, It Becomes Less Soluble & ‘Gels’ This Changes The Shape Of The Erythrocytes. They Become ‘Sickle’ Shaped They Increase The Blood Viscosity And Undergo Hemolysis. This Is A Serious Condition, Can Be Fatal By Middle Age. 16  Hb: PATHOLOGICAL : THALASSEMIAS defect in the synthesis of either alpha & beta chains of globin. beta thalassemia is more common. beta chain not formed. rapid hemolysis occurs in vivo. causes hypochromic anemia. 17  Life Span and Fate of RBCs The life span of RBCs is 120 days. Fate: RBCs cannot reproduce (Why?). They are fragile and rupture easily while passing through tiny vessels especially in the spleen. Jaundice Yellow coloration of skin, sclera Deposition of bilrubin in tissues If Bilrubin level in blood > 2 mg/ ml > jaundice 18  ERYTHROPOIESIS: SITES/PHASES It is the process of the formation of RBCs. INTRAUTERINE LIFE: Liver & Spleen post natal life: Children: Predominantly Red Bone Marrow of skeleton: Axial & Appendicular. Adults: Red Bone Marrow of Axial Skeleton. 19  Production of Erythrocytes: Erythropoiesis Features of the maturation process of RBC 1.Reduction in size 2.Disappearance of the nucleus 3.Acquisition of haemoglobin ‫بداية تكوين الهيموجلوبين‬ ‫يجب استقبال هرمون‬ ‫تفقد النواة بين مرحلتي‬ erythropoietin Normoblast ‫و‬ ‫لالنتقال لمرحلة‬ Reticulocyte committed cell Erythrocyte  FACTORS REGULATING Factors Affecting Erythropoiesis ERYTHROPOIESIS 1- Decreased O2 supply to the tissues (Hypoxia): Decreased O2 supply to the tissues stimulates RBCs production. Hypoxia stimulates erythropoiesis due to the stimulation of the release of erythropoietin hormone. Erythropoietin hormone is produced by the kidney 85% and the liver 15%. ⮚ Effect: ⮚ a, Stimulates the proliferation and differentiation of the committed red cell precursor ⮚ b, Accelerates hemoglobin synthesis ⮚ c, Shortens the period of red development in the bone marrow. 21  Role of the kidneys in RBC formation Hypoxia, (blood loss) ↓ ↓ Blood O2 levels ↓ Tissue (kidney) hypoxia ↓ ↑ Production of erythropoietin ↓ ↑ plasma erythropoietin ↓ Stimulation of erythrocytes production ↓ ↑ Erythrocyte production  Factors Affecting Erythropoiesis 2- Dietary factors: A- Proteins: High biological value proteins are needed for the formation of globin. B- Vitamins: 1- Vitamin B12 (Maturation factor- Extrinsic factor- Cyanocobalamin): Function: It is essential for the synthesis of DNA and maturation of RBCs. It is important for the formation of myelin sheath. 23  Factors Affecting Erythropoiesis (cont.) B- Vitamins (cont.): 1- Vitamin B12: Absorption: It is absorbed in the lower ileum. Its absorption needs intrinsic factor secreted by the stomach. It is stored in the liver. Deficiency: Failure of nuclear maturation and division of erythroblasts in the bone marrow. The erythroblasts increase in size (megaloblasts) with shorter life span. The cells become large in size with decreased number thus producing macrocytic anemia. Deficiency of intrinsic factor produces macrocytic anemia called pernicious anemia which is treated by vitamin B12 injections (why?). 24  Factors Affecting Erythropoiesis (cont.) B- Vitamins (cont.): 2- Folic acid: Source: Green vegetables and fruits. Deficiency: Similar in action to vitamin B12 and its deficiency also produces macrocytic anemia. 25  VITAMINS B12: Is also called Extrinsic Factor. Needs the Intrinsic Factor from the Gastric juice for absorption from Small Intestine. Deficiency causes Pernicious (When IF is missing) or Megaloblastic Anemia. Stimulates Erythropoiesis Is found in meat & diary products. 26  Factors Affecting Erythropoiesis (cont.) C- Iron: Function: Formation of Hemoglobin. Absorption: 1- Most dietary iron is in the Fe3+ form. 2- It must be reduced to the Fe2+ form to be absorbed. This occurs by gastric HCl and vitamin C in the diet. 3- Iron absorption occurs in the upper part of the small intestine. 4- After absorption it is oxidized to Fe3+ form. Transport: It is transported in the blood as transferrin. Fe3+ + apotransferrin transferrin. Storage: It is stored in the liver as ferritin. Fe3+ + apoferritin ferritin. Deficiency: Iron deficiency produces microcytic anemia. This anemia is characterized by cells with small size and decreased 27 amount of Hemoglobin.  Factors Affecting Erythropoiesis (cont.) 3- Hormones: 1- Testosterone hormone stimulates erythropoietin secretion. 2- Thyroid hormones increase cell metabolism. 3- Cortisol hormone increases formation of RBCs. 4- Estrogen – inhibit erythropoiesis 4- Healthy Liver: Importance of the liver: 1- Forms globin. 2- Stores iron and vitamin B12. 3- Produces 15% of erythropoietin. 5- Healthy Bone Marrow: It is the site of erythropoiesis. It is destroyed by irradiation and tumors. 28  ANEMIAS Deficiency of Hb in the blood caused by either: ↓RBC Count or ↓ Hb in the RBCs It leads to a decrease in O2 supply to the tissues. The tissues suffers from disturbances in their functions. 29  Anemia according to the causes Deficiency anemia; Due to deficiency of one of the main factors share in formation of RBCs. Sickle cell anemia. Thalassaemia. Aplastic anemia. Iron deficiency anemia. Pernicious anemia. Haemorrhagic anemia: Acute hemorrhage chronic hemorrhage. Hemolytic anemia Due to toxins, drugs or snake venoum.  Classifications of anaemia According to the volume of RBCs and hemoglobin content of red blood cells, anemia could be classified into three main types: 1- Microcytic hypochromic anemia: - Red cells are of small volume - very low content of Hb. - It is mostly due to iron deficiency anemia 2- Macrocytic hypochromic anemia: - The red cells are of large size - The hemoglobin content is low. - It is called megaloblastic anemia. - It is due to deficiency of vit B12 or due to deficiency of folic acid.. 2- Normocytic normochromic anemia: - Size of RBCs is normal. - colour of RBCs is normal (contain normal amount of hemoglobin) - total RBCs count & Hb content is lower than normal. - seen in cases of acute blood loss, hemolytic anemia and aplastic anemia.  1. HEMORRHAGIC ANEMIA (BLOOD LOSS) ACUTE: Sudden loss of blood Normocytic normochromic anemia CHRONIC BLOOD LOSS: They cannot absorb Fe enough to form Hb Have Hypochromic, Microcytic Anemia. 32  2. APLASTIC ANEMIA: Lack of functioning Red Bone Marrow, the hemopoietic tissue. Caused by exposure to gamma ray radiation (Nuclear Bomb Blast) Excessive exposure to X rays Exposure to certain industrial chemicals. NOMAD:2006: BP: HBANEM 33  3. MEGALOBLASTIC ANEMIA: Deficiency of Vit B12 and or Folic Acid. Intrinsic Factor can also be deficient. Production of Erythrocytes becomes slow. They remain large, hve odd shapes and are called ‘Megaloblasts’ Atropy of Stomach mucosa can cause loss of Intrinsic factor & this anemia is called Pernicious Anemia. 34  4. HEMOLYTIC ANEMIAS Mostly hereditary. Cells are fragile, rupture easily as they move through the capillaries. The life span of erythrocytes is reduced. HERIDITARY SPHEROCYTOSIS: Small spherical erythrocytes. Cannot be compressed even slightly Rupture and are lysed very easily. 35  5. SICKLE CELL ANEMIA The Beta chains of Hemoglobin are defective? They have Hb S Sickling occurs when Hb loses Oxygen. A vicious circle of events occurs: ↓ Oxygen tension ⭢ Sickling ⭢ Rupture of Erythrocytes ⭢ Further ⭣ Oxygen tension 36 NOMAD:2006: BP: HBANEM 37  IRON DEFICIENCY ANEMIA The most common type of anemia. Caused by nutritional deficiency of Iron. Erythrocytes are smaller and have less Hb. So they are called Microcytic & Hypochromic. Treated by taking Iron rich diets. 38  SECONDARY ANEMIA (RENAL) Renal Diseases can cause decreased Erythropoietin. Erythropoietin is essential for proper production of erythrocytes (Erythropoiesis) Renal disease thus causes Anemia. 39  Polycythemia Increased number of RBC Types: True or absolute Primary (polycythemia rubra vera): uncontrolled RBC production Secondary to hypoxia: high altitude, chronic respiratory or cardiac disease Relative Haemoconcentration: loss of body fluid in vomiting, diarrhea, sweating  REVIEW Hemoglobin is a chromoprotein present exclusively within the erythrocytes. Hb synthesis takes place within the normoblasts. Hemoglobin = Heme + Globin. Heme is an Iron containing Porphyrin. Iron is present in the Ferrous form. Oxygen can be loosely attached to Hb. 41  REVIEW Normal blood levels of Hemoglobin: Males : 14 – 18 Gm% Females : 12 – 15 Gm% 1 Gram of Hemoglobin combines with 1.34 ml of Oxygen. Varieties of Hemoglobin include: Hb A, Hb F Hb S, Hb A2 42  REVIEW Anemia is a decrease in either Hb or RBCs. Types of Anemia: Hemorrhagic Aplastic Megaloblastic Pernicious Hemolytic Sickle Cell Iron deficiency Secondary (Renal) NOMAD:2006: BP: HBANEM 43 Thank You