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Lecture 8

Introduction & Basics of Red Blood Cells

Bones with active hematopoiesis (1) Vertebra (2) Ribs (3) Sternum (4) Skull (5) Pelvis (6) Scapula (7) Proximal long bones
Source of Erythopoitein Kidney (peritubular interstitial cells)
Function of Erythorpoietin in vivo Increases RBC production, Hgb F, and marrow cellularity.
Clinical use of Erythropoietin Anemia of renal failure, chronic diseae, and malignancy
Source of G-CSF (Granulocyte Colony Sitmulating Factor) (1) Monocytes (2) Fibroblasts (3) Endothelial Cells
Function of G-CSF (1) Increases white cell count (2) Increases granulocyte release from bone marrow (3) Stimulates CFU-G in bone marrow
Clinical use of G-CSF Acquired and congential neutropenias
Source of IL-6 IL-1 or TNF activated endothelial cells and T cells
Function of IL-6 Increases platelet production
Source of SCF (Stem Cell Factor) Fibroblasts, marrow stromal cells
Function of SCF Important for maintaining functional bone marrow microenvironment. Deficiency also may produce anemias.
Source of IL-5 Marrow stromal cells
Source of IL-11 Fibroblasts
Function of IL-5 In vitro it is a eosinophil growth factor and stimulates lymphocytes
Function of IL-11 (1) Raises platelet count (2) Synergistic with IL-3, IL-6, G-CSF, and SCF
Percentage of Erythropoietin produced constitutively in the liver 10% of total body erythropoietin
What cytokines induce G-CSF production by fibroblasts, macrophages, and endothelial cells? IL-1, IL-6, and TNF-alpha
Organs that constitutively produce thrombopoietin (1) Liver (50%) (2) Kidney (minority)
How is thrombopoietin induced? (1) Induced in the liver by IL-6 (2) Thrombocytopenia induces production in marrow stromal cells
Earliest identifiable erythroid cells Erythroblasts
List the stages of Erythrocyte maturation (1) Erythroblast (2) Basophilic normoblast (3) Polychromatic normoblast (4) Orthochromatic normoblast (5) Reticulocyte (6) Erythrocyte
What stage of erythrocyte maturation is the nucelus extruded from the cell? Orthochromatic normoblast
Percentage of erythrocytes that reside in the peripheral blood 95%
Lifespan of erythrocyte 120 days
What percentage of the red blood cell mass is replaced in a 24 hour period? Over 1%
What mediates erythropoietin production? Tissue oxygen levels
(T or F) Erythropoietin production is mediated by red blood cell mass. False. The production of erythropoietin is mediated by tissue oxygen levels.
A glycoprotein that is the major regulator of erythrocyte production. It simulates the differentiation of committed erythroid stem cells into red cell precursors. Erythropoietin
What is the myeloid to erythroid ratio? M:E = 3:1. There are normally 3 myeloid precursors for each erythroid precursor.
How does accelerated red cell production affect the myeloid to erythroid ratio (M:E ratio)? Acelerated red cell production is assoicated with a decreased M:E ratio.
Describe the components of hemoglobin Hemoglobin consists of a large protein called globin. The globin consists of 4 polypeptide chains arranged in pairs:2 alpha and 2 beta chains. The globin protein is coupled to 4 porphyrins. Porphyrins are heme moieties that each contain 1 iron atom.
Globin chains of Hemoglobin A 2 alpha chains and 2 beta chains
Globin chains of Hemoglobin A2 2 alpha chains and 2 delta chains
Globin chains of Hemoglobin F 2 alpha chains and 2 gamma chains
What percentage of adult hemoglobin consists of Hgb A? Approximately 95%
What percentage of fetal hemoglobin consists of HgF? >50%
What percentage of adult hemoglobin consists of Hgb A2? <3.5%
What percentage of adult hemoglobin consists of Hgb F? <1%
Energy source of erythrocytes Anaerobic glycolysis (Embden-Meyerhof pathway) and hexose-monophosphate shunt (pentose phosphate pathway)
Form of iron that transport oxygen Reduced iron (Fe++)
Enzyme that catalyzes methemoglobin reduction of Fe(3+) hemoglobin to its functional Fe(2+) form Methemoglobin reductase. This enzyme uses NADH generated during glycolysis.
Metabolic pathway that prevents oxidative damage of hemoglobin in erythrocytes Hexose-monophohate shunt
Heinz bodies Precipated hemoglobin due to denaturation of the protein
How is the oxygen affinity of hemoglobin modulated by 2,3-biphosphoglycerate (2,3-DPG)? Glycolysis leads to an increase in intracellular 2,3-DPG concentration. When venous blood is deosygenated the rate of glycolysis increases leading to increased 2,3-DPG production and increased oxygen release to the tissues.
Anisocytosis Variation in red cell size
Poikilocytosis Variation in red cell shape
Schisotcytes Fragmented red cells; torn or split or broken by physical means.
Target cells Red cells in which the hemoglobin appear concentrated in the center of the cell in a target or bulls-eye configuration.
Spherocytes Spherical red cells without central pallor.
Ovalocyte Egg shaped red cells
Elliptocytes Oblong or ellipsoidal red cells with nearly parallel sides.
Sickle cell Thin, curved, fusiform, sickle shaped cells. Often the cells have pointed ends.
Acanthocyte A spiny spiked red cell without central pallor.
Burr cell A red cell with knobby surface bumps.
Catabolic product of the ringed structures of heme Bile pigments (biliverdin)
A disease process of heme biosynthesis caused by a defect in porphobilinogen demainase causing abdominal pain and neurologic deficits such as motor paralysis. Acute intermitten porphyria
A disease process of heme biosynthesis caused by a defect in protoporphyrinogen oxidase causing abdominal pain, neurologic deficits, and sensitivity to light. Variegate porphyria
A disease process of heme biosynthesis caused by a defect in uroprophyrinogen decarboxylase that is usually is asymptomatic, but may cause dermal photo sensitivity with specific triggers. Porphyria cutanea tarda
A disease process of heme biosynthesis due to decreased heme synthetase causing increased dermal photosensitivity. Protoporphyria
Definition of Hematocrit (Hct) Volume of packed red cells expressed as a percentage. It only indirectly reflects the RBC mass.
Normal range of hematocrit for a term newborn .53-.68 L/L
Normal range of hematocrit for an infant (3 months) .30-.38 L/L
Normal range of hematocrit for a child (10 years) .37-.44 L/L
Normal range of hematocrit for an adult female .35-.47 L/L
Normal range of hematocrit for an adult male .40-.52 L/L
Definition of Hemoglobin (Hgb) Grams of hemoglobin per liter of whole blood (g/L)
Normal range of hemoglobin of an adult female 120-160 g/L
Normal range of hemoglobin of an adult male 130-180 g/L
Units of Red Blood Cell Count (RBC) Number of RBCs (x10^12/L)
Normal range of red blood cell count of an adult female 3.8-5.2 x 10^12/L
Normal range of red blood cell count of an adult male 4.4-5.9 x 10^12/L
Definition of Mean Corpuscular Hemoglobin (MCH) Average weight of Hgb in a RBC (pg/RBC). MCH = Hgb/RBC
Normal range of MCH 26-34 pg
Definition of Mean Corpusuclar Hemoglobin Concentration (MCHC) Hemoglobin concentration of the average RBC (g/L). MCHC = Hgb/Hct
Normal range of MCHC 320-360 g/L
Defintion of Red Cell Distribution Width (RDW) Coefficient of variation about the mean RBC size. It is a quantitiative measurement of variation in RBC size (anisocytosis)
Definition of Reticululocyte Red cells that contain residual RNA identified with new methylene blue stain. The remanants of RNA or polyribosomes signal a cell that has entered the vascular circulation recently. It is an index of hte number of newly formed erythrocytes in the blood.
Normal range of reticulocyte count 25,000-75,000/microLiter or 1%
(T or F) The percentage of reticulocyte is a reliable marker of RBC production in the setting of anemia. False. In anemic patients, the percentage of reticulocytes is less meaningful since the total number of RBC is reduced. Also, reticulocytes are released earlier from the bone marrow under anemic stress.
How is Hgb catabolism best measured or monitored? Serum indirect bilirubin and LDH
Expected reticulocyte count in the setting of hemolytic anemia Increased reticulocytes
Expected effect on reticulocyte count in the setting of anemia due to hypoproliferation Decreased reticulocytes
Expected effect on reticulocyte count in the setting of anemia due to ineffective erythropoiesis Decreased reticulocytes
Expected marrow myeloid to erythroid ratio in the setting of hemolytic anemia Decreased marrow M:E ratio
Expected marrow myeloid to erythroid ratio in the setting of anemia due to hypoproliferation Increased marrow M:E ratio
Expected marrow myeloid to erythroid ratio in the setting of anemia due to ineffective erythropoiesis Decreased marrow M:E ratio
Under hypoxic/anemic stimulus, when does the initial reticulocyte response occur? 2-3 days
(T or F) The degree of anemia influences the intensity of stimulation of red cell production. True.
Created by: UVAPATH4
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