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Physiology Lecture 62

Physiology Lecture 62. Tanveer Raza MD MS MBBS razajju2@yahoo.com. Red Blood Cells. Also knowqn as Erythrocytes RBC Red blood Corpuscles Most common type of blood cell Main function is to transport Oxygen. Red Blood Cells. Contains hemoglobin, an iron-containing pigment

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Physiology Lecture 62

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  1. Physiology Lecture 62 Tanveer Raza MD MS MBBS razajju2@yahoo.com

  2. TanveerRaza MD MS MBBS razajju2@yahoo.com

  3. Red Blood Cells • Also knowqn as • Erythrocytes • RBC • Red blood Corpuscles • Most common type of blood cell • Main function is to transport Oxygen TanveerRaza MD MS MBBS razajju2@yahoo.com

  4. Red Blood Cells • Contains hemoglobin, • an iron-containing pigment • Responsible for the blood's red color. • Flexible biconcave disks • Lack a cell nucleus and most organelles • Life Span 120 days TanveerRaza MD MS MBBS razajju2@yahoo.com

  5. Red Blood Cells (RBC’s) • Function • Respiratory Function • Transports O2 from lungs to tissues • CO2 from lungs to tissues • Acid-base buffer Also • Viscosity of blood • Contains antigen • Various pigments • Ion balance TanveerRaza MD MS MBBS razajju2@yahoo.com

  6. Red Blood Cells (RBC’s) • Contains large quantity of carbonic anhydrase • Catalyzes the reversible reaction between CO2 and H2O • Increases reaction rate several thousand fold • Enables blood to transport large quantities of CO2 as HCO3- from tissues to lungs TanveerRaza MD MS MBBS razajju2@yahoo.com

  7. Red Blood Cells (RBC’s) • Shape and Size of RBC’s • Normal RBC’s are biconcave discs • Mean diameter 7.8 micrometers • Thickness • 2.5 micrometers at the thickest point • 1 micrometer or less in the center • Average volume 90-95 cubic micrometers TanveerRaza MD MS MBBS razajju2@yahoo.com

  8. Red Blood Cells (RBC’s) • Shapes • Can change remarkably as the cells squeeze through capillaries • Like a bag • Change of shape do not stretch the membrane • As RBC cell has a great excess of cell membrane TanveerRaza MD MS MBBS razajju2@yahoo.com

  9. Red Blood Cells (RBC’s) • Average concentration of RBC in blood • In normal men • 5,200,000 (±300,000)/ cubic millimeter of blood • In normal women • 4,700,000 (±300,000)/ cubic millimeter of blood TanveerRaza MD MS MBBS razajju2@yahoo.com

  10. Red Blood Cells (RBC’s) • Each gram of pure Hb combines with 1.34 ml of O2 • Amount of Hemoglobin • Men 15 grams/100 ml of cells • 20 ml of O2 carried in combination with Hb in each 100 ml of blood • Women 14 grams/100 ml of cells • 19 ml of O2 carried in combination with Hb in each 100 ml of blood TanveerRaza MD MS MBBS razajju2@yahoo.com

  11. Red Blood Cells (RBC’s) • Hematocrit or Packed Cell Volume (PCV) • Percentage of blood that is cells • Normally, 40-45% TanveerRaza MD MS MBBS razajju2@yahoo.com

  12. RBC’s: Erythropoiesis • Production of RBC’s (Erythropoiesis) • In the early weeks of embryonic life • Yolk sac • Primitive, nucleated red blood cells • During middle trimester of gestation • Liver Also • Spleen • Lymph nodes TanveerRaza MD MS MBBS razajju2@yahoo.com

  13. RBC’s: Erythropoiesis • During last month or so of gestation and after birth • Bone marrow Relative rates of RBC production in the bone marrow of different bones at different ages TanveerRaza MD MS MBBS razajju2@yahoo.com

  14. RBC’s: Erythropoiesis • During the last month or so of gestation and after birth • Bone marrow • Until 5 years old • All bones produces RBC • Upto 20 years of age • Proximal portions of the humerus and tibia (Red marrow) • Marrow of long bones, except for the becomes quite fatty (Yellow marrow) TanveerRaza MD MS MBBS razajju2@yahoo.com

  15. RBC’s: Erythropoiesis • Last month of gestation and after birth • Bone marrow • Beyond 20 years of age • Produced in the marrow of the membranous bones, such as the vertebrae, sternum, ribs, and ilium • Even in these bones, marrow becomes less productive as age increases TanveerRaza MD MS MBBS razajju2@yahoo.com

  16. Pluripotential hematopoietic stem cell Committed stem cells/Colony-forming unit-erythrocyte (CFU-E) Proerythroblast Basophil Eryhthroblast Polychromatophil eryhtroblast Orthochromatic erythroblast Reticulocyte Erythrocytes

  17. TanveerRaza MD MS MBBS razajju2@yahoo.com

  18. RBC’s: Erythropoiesis • Pluripotential hematopoietic stem cell • All the blood cells begin in the bone marrow from a single type of cell • Committed stem cells • Very much like pluripotential stem cells • Already committed to be a particular line of cells • Colony-forming unit-erythrocyte (CFU-E) produces erythrocytes TanveerRaza MD MS MBBS razajju2@yahoo.com

  19. RBC’s: Erythropoiesis • Proerythroblast • Formed from CFU-stem cells • Basophil Eryhthroblast • Stain with basic dyes • Very little Hb TanveerRaza MD MS MBBS razajju2@yahoo.com

  20. RBC’s: Erythropoiesis • In the succeeding generations cells become filled with Hb to a concentration of about 34 per cent, the nucleus condenses to a small size, and its final remnant is absorbed or extruded from the cell. At the same time, the endoplasmic reticulum is also reabsorbed TanveerRaza MD MS MBBS razajju2@yahoo.com

  21. RBC’s: Erythropoiesis • Reticulocyte • RBC still contains a small amount of basophilic material, consisting of remnants of the Golgi apparatus, mitochondria, and a few other cytoplasmic organelles • Cells pass from the bone marrow into the blood capillaries by diapedesis TanveerRaza MD MS MBBS razajju2@yahoo.com

  22. RBC’s: Erythropoiesis • Reticulocyte • The remaining basophilic material in the reticulocyte normally disappears within 1 to 2 days, and the cell is then a mature erythrocyte • Because of the short life of the reticulocytes, their concentration among all the RBC of the blood is normally slightly less than 1% TanveerRaza MD MS MBBS razajju2@yahoo.com

  23. RBC’s: Erythropoiesis • Growth Inducers • Controls growth and reproduction of the different stem cells • Growth inducers promote growth but not differentiation of the cells • Interleukin-3 • Promotes growth and reproduction of virtually all the different types of committed stem cells TanveerRaza MD MS MBBS razajju2@yahoo.com

  24. RBC’s: Erythropoiesis • Diffenrentiation Inducers • Causes one type of committed stem cell to differentiate one or more steps toward a final adult blood cell. TanveerRaza MD MS MBBS razajju2@yahoo.com

  25. RBC’s:Regulation of Erythropoiesis Function of the erythropoietin mechanism to increase production of red blood cells when tissue oxygenation decreases. TanveerRaza MD MS MBBS razajju2@yahoo.com

  26. RBC’s:Regulation of Erythropoiesis • Tissue Oxygenation • Most Essential • Conditions decreasing O2 transported to tissues usually increase RBC production • Example • Decreased RBC: Hemorrhage • Decreased O2 in air: Very high altitudes • Decreased blood flow: Cardiac failure Many lung diseases TanveerRaza MD MS MBBS razajju2@yahoo.com

  27. RBC’s:Regulation of Erythropoiesis • Erythropoietin (EPO) • Hormone • Controls Eryhtropoieis • Under hypoxic conditions, kidney will produce and secrete EPO to increase the production of RBC by targeting CFU-E • In the absence of EPO, hypoxia has little or no effect in stimulating RBC production TanveerRaza MD MS MBBS razajju2@yahoo.com

  28. RBC’s:Regulation of Erythropoiesis • Erythropoietin (EPO) • Site of production • Kidney 90% • Liver TanveerRaza MD MS MBBS razajju2@yahoo.com

  29. RBC’s:Regulation of Erythropoiesis • Maturation of RBC • Vitamin B12 (Cyanocobalamin) and Folic Acid • Essential for DNA synthesis • Deficiency gives rise to maturation failure • Cells carry same oxygen but more fragile (short life span) • Larger than normal (Macrocytes) • Oval shaped • Flimsy membrane TanveerRaza MD MS MBBS razajju2@yahoo.com

  30. RBC’s:Regulation of Erythropoiesis • Pernicious anemia • Type of megaloblastic anemia • Usual cause atrophic gastritis • Autoimmune destruction of gastric parietal cells causing lack of intrinsic factor • Deficiency of Vitamin B12 • Absorption of Vit B12 from the gut is dependent on intrinsic factor • May be fatal type due to peripheral nerve damage TanveerRaza MD MS MBBS razajju2@yahoo.com

  31. RBC’s:Regulation of Erythropoiesis • Deficiency of Folic Acid • Folic acid is a normal constituent of green vegetables, some fruits, and meats (especially liver) • Easily destroyed during cooking • Gastrointestinal absorption abnormalities, • Such as Sprue • Serious difficulty in absorbing both folic acid and Vit B12 TanveerRaza MD MS MBBS razajju2@yahoo.com

  32. RBC: Formation of Hemoglobin TanveerRaza MD MS MBBS razajju2@yahoo.com

  33. RBC: Formation of Hemoglobin • Study the picture • Begins in the proerythroblasts • Continues into the reticulocyte stage of RBC • Hemoglobin chain • Each chain has a MW of about 16,000 • 4 of these in bind together loosely to form the whole Hb molecule TanveerRaza MD MS MBBS razajju2@yahoo.com

  34. RBC: Formation of Hemoglobin • Hemoglobin molecule • 4 Hb chains • Each contain one Heme • Each heme bind with one atom of Iron • Each Iron atom bind with one O2 molecule • Thus, One molecule of Hb (4 Hb chains) bind with 4 molecules of O2 • Eight Oxygen atoms TanveerRaza MD MS MBBS razajju2@yahoo.com

  35. RBC: Formation of Hemoglobin • Hemoglobin chain • Types of chains • Alpha (α) chains • Beta (β) chains • Gamma (γ) chains • Delta (δ) chains • Hemoglobin A • Most common form of Hb in adults • Combination of 2α and 2β chains • MW 64,458 TanveerRaza MD MS MBBS razajju2@yahoo.com

  36. RBC: Formation of Hemoglobin • Hemoglobin chain • Some other types in humans • Hemoglobin F (α2γ2) • In the fetus • Hemoglobin A2 (α2δ2) • In adults • Hemoglobin H (β4) • In some forms of α thalassemia • Hemoglobin S (α2βS2) • Sickle cell disease TanveerRaza MD MS MBBS razajju2@yahoo.com

  37. RBC • Life Span and Destruction of RBC’s • Average Life Span 120 days • The RBC membrane becomes fragile, the cell ruptures during passage through some tight spot of the circulation • Spleen TanveerRaza MD MS MBBS razajju2@yahoo.com

  38. RBC TanveerRaza MD MS MBBS razajju2@yahoo.com

  39. RBC • Destruction of Hemoglobin • Iron • The macrophages release iron from the Hb and pass it back into the blood, to be carried by transferrin either to the bone marrow for the production of new RBC or to the liver and other tissues for storage in the form of ferritin TanveerRaza MD MS MBBS razajju2@yahoo.com

  40. RBC • Destruction of Hemoglobin • Porphyrin • The porphyrin portion of Hb is converted by the macrophages into the bile pigment bilirubin TanveerRaza MD MS MBBS razajju2@yahoo.com

  41. Thank You

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