Blood Cells Immunity and Blood Clotting RED BLOOD
Blood Cells, Immunity, and Blood Clotting RED BLOOD CELLS, ANEMIA, AND POLYCYTHEMIA
Red Blood Cells, Anemia, and Polycythemia RED BLOOD CELLS Functions ❑ transport hemoglobin, w/c in turn carries O 2 from lungs to tissues ➢ Hemoglobin to remain in the blood stream, must exist inside red blood cells ❑ contain a large quantity of carbonic anhydrase, that catalyzes reversible reaction between carbon dioxide CO 2 & H 2 O to form H 2 CO 3 ❑ responsible for the acid-base buffering power of whole blood ❑ ❑ ❑ biconcave discs mean diameter = 7. 8 μM thickness = 2. 5 μM at thickest point & 1 μM or less in the center
Red Blood Cells, Anemia, and Polycythemia ❑ Maximum Hgb concentration - 34 g/100 ml of cells ❑ Normal Hgb concentration – - 15 g/100 ml of blood - 14 g/100 ml of blood ❑ 1 g of pure Hgb can combine w/1. 34 ml of O 2 ❑ Normal values RBC count: - 5, 200, 000 (± 300, 000) - 4, 700, 000 (± 300, 000) Hematocrit (% of blood that is cells) - 40 to 45% ❑ Oxygen carrying capacity of blood - 20 ml of O 2/100 ml of blood - 19 ml of O 2/100 ml of blood
Red Blood Cells, Anemia, and Polycythemia Production of Red Blood Cells ❑ Areas of the body that produce red blood cells ➢ Yolk sac – 1 st trimester ➢ Liver (also spleen & lymph nodes – 2 nd trimester ➢ Bone marrow – 3 rd trimester ❖ All bones – until 5 yrs ❖ Long bones – until 20 yrs ❖ membranous bones (vertebrae, sternum, ribs, & ilia – beyond 20 yrs
Red Blood Cells, Anemia, and Polycythemia Pluripotential hematopoietic stem cell - all cells of the blood are derived from this cells reproduce cells differentiate to form other cell types committed stem cells ➢ ➢ colony-forming unit erythrocyte (CFU-E) CFU-GM Formation of different blood cells from pluripotent hematopoietic stem cell (PHSC) in the bone marrow
Red Blood Cells, Anemia, and Polycythemia Genesis of Blood Cells ❑ Growth inducers (e. g. interleukin-3) ➢ ❑ promotes growth & reproduction of all the different types of committed stem cells Differentiation inducers ➢ cause one type of committed stem cell to differentiate one or more steps toward a final adult blood cell Formation of different blood cells from pluripotent hematopoietic stem cell (PHSC) in the bone marrow
Red Blood Cells, Anemia, and Polycythemia Stages of Differentiation of Red Blood Cells Proerythroblast - first cell identified as belonging to RBC series. basophil erythroblast stains w/ basic dyes; has very little hemoglobin cells become filled w/ Hgb (34% conc. ); nucleus condenses & absorbed. ER is also reabsorbed. Cell is now a reticulocyte Reticulocyte - small amount of basophilic material (remnants of Golgi apparatus, mitochondria, & a few other organelles ) Diapedesis – from marrow blood basophilic material in reticulocyte disappears w/in 1 to 2 days after entry into blood. Cell now a mature erythrocyte
Red Blood Cells, Anemia, and Polycythemia Regulation of Red Blood Cell Production—Role of Erythropoietin ❑ Tissue oxygenation is the most essential regulator of RBC production ❑ Erythropoietin stimulates RBC production. Its formation increases in response to hypoxia
Red Blood Cells, Anemia, and Polycythemia Maturation of RBCs — Requirement for Vitamin B 12 (Cyanocobalamin) & Folic Acid ❑ Vitamin B 12 & folic acid are important for final maturation of the RBCs. ❑ Both are essential for synthesis of DNA ❑ Vitamin B 12 absorption needs intrinsic factor w/c are secreted by gastric parietal cells Absorption of B 12 1. INTRINSIC FACTOR binds tightly w/ vitamin B 12. Bound B 12 protected from digestion by GIT secretions. 2. Still in bound state, intrinsic factor binds to receptor sites on the brush border of membranes of cells in ileum. 3. B 12 transported into blood in few hours by pinocytosis, carrying intrinsic factor & vitamin thru the membrane
Red Blood Cells, Anemia, and Polycythemia Formation of Hemoglobin Each of the 4 iron atoms can bind loosely w/ 1 molecule of O 2, making a total of 4 molecules of O 2 (or 8 oxygen atoms)/Hgb molecule Structure of Hgb molecule, showing one of the 4 heme chains that bind together to form the Hgb molecule.
Red Blood Cells, Anemia, and Polycythemia Combination of Hgb w/ O 2 ❑ O 2 does not combine w/ the two positive bonds of the iron in the Hgb. ❑ O 2 binds loosely w/ one of the coordination bonds of the iron atom. ➢ An extremely loose, easily reversible bond. ❑ Furthermore, the O 2 does not become ionic oxygen but is carried as molecular oxygen (composed of 2 oxygen atoms). Structure of Hgb molecule, showing one of the 4 heme chains that bind together to form the Hgb molecule.
Red Blood Cells, Anemia, and Polycythemia Iron Distribution ❑ Total body iron = 4– 5 g ➢ 65% - part of Hgb. ➢ 4% - part of myoglobin 1% - heme compounds (cytochromes, cytochrome oxidase, peroxidase, catalase) ➢ ➢ 0. 1% - bound to transferrin 15 – 30% stored in RES & liver in the form of ferritin (storage iron) Transport and Storage of Iron
Red Blood Cells, Anemia, and Polycythemia Iron Absorption Steps 1. Liver secretes apotransferrin in bile 2. In duodenum. apotransferrin binds w/ free iron & also w/ iron compounds, such as Hgb & myoglobin from meat. 3. The transferrin formed binds w/ receptors in intestinal cells, absorbed by pinocytosis & later released into capillaries in the form of plasma transferrin. ❑ Iron absorption is very slow, (a few mg/day) ❑ Total body iron is controlled mainly by altering rate of absorption Transport and Storage of Iron
Red Blood Cells, Anemia, and Polycythemia ❑ Mature RBCs life span – 120 days ❑ do not have a nucleus, mitochondria, or endoplasmic reticulum ❑ have cytoplasmic enzymes that: metabolize glucose form small amounts of ATP. maintain pliability of membrane maintain membrane ion transport keep iron of the Hgb in the ferrous form rather than ferric form prevent oxidation of proteins in RBCs ➢ ➢ ➢
Red Blood Cells, Anemia, and Polycythemia Life Span & Destruction of RBCs ❑ After 120 days RBCs burst & release Hgb ❑ Hgb is phagocytized by macrophages (especially by hepatic Kupffer cells & macrophages of spleen & bone marrow). ❑ macrophages release iron from the Hgb into blood, & carried by transferrin either to ❑ Porphyrin portion of Hgb converted by macrophages into bilirubin, released the bone marrow or to the into blood & later secreted thru the liver & other tissues. into the bile
Red Blood Cells, Anemia, and Polycythemia Blood Loss Anemia ❑ ➢ Aplastic Anemia. After rapid hemorrhage Normocytic; RBC count low ❑ Bone marrow aplasia ➢ lack of functioning bone marrow (acellular bone marrow) In chronic blood loss Microcytic, hypochromic ❑ Causes ➢ exposure to gamma ray radiation ➢ excessive x-ray treatment ➢ certain industrial chemicals ➢ Some drugs
Anemia, and Polycythemia
Red Blood Cells, Anemia, and Polycythemia ❑ ❑ Megaloblastic Anemia Due to maturation failure caused by poor absorption of vitamin B 12 from GIT Pernicious Anemia Due to maturation failure caused by folic acid dietary deficiency ❑ Pathology of macrocytes ❑ ➢ ➢ ➢ Causes of B 12 deficiency Gastric atrophy (pernicious) Gastrectomy (pernicious) Ileal resection (pernicious) Chronic inflammation of ileum (pernicious) Dietary deficiency (dietary) ➢ failure to proliferate rapidly ➢ larger than normal red cells called macrocytes (megaloblastic anemia) ➢ cell has flimsy membrane Rx for dietary anemia – Oral B 12 + folic acid Rx for pernicious - Parenteral B 12
Red Blood Cells, Anemia, and Polycythemia Hemolytic Anemia ❑ Fragile cells; shortened lifespan ❑ Examples ➢ hereditary spherocytosis o red cells are very small & spherical ➢ sickle cell anemia o abnormal type of Hgb (Hgb S, containing faulty beta chains) o precipitates into long crystals inside RBC on exposure to low PO 2 ➢ erythroblastosis fetalis o Rh(+) RBCs in fetus are attacked by antibodies from an Rh (-) mother
Red Blood Cells, Anemia, and Polycythemia ❑ ❑ ➢ Red cell count reaches 6 to 7 million/mm 3 Secondary polycythemia Due to chronic hypoxia (CHF, emphysema, high altitude) physiologic polycythemia in natives who live at altitudes of 14, 000 to 17, 000 feet, where the atmospheric PO 2 is very low ➢ ❑ Polycythemia Vera (Erythremia). ➢ genetic aberration in hemocyto -blastic cells that produce the blood cells ➢ RBC count > 7 million/mm 3 ➢ Hct > 60% ➢ Increased blood viscosity ➢ ruddy complexion w/ a bluish (cyanotic) tint to the skin.
END – THANK YOU RED BLOOD CELLS, ANEMIA, AND POLYCYTHEMIA
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