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Lecture 8
Introduction & Basics of Red Blood Cells
| Question | Answer |
|---|---|
| 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. |
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UVAPATH4
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