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