Erythrocyte Metabolism

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Erythrocyte Metabolism
2011-05-23 11:03:34
Erythrocyte Metabolism

Erythrocyte Metabolism
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  1. How is energy generated for Erythrocytes?
    Anaerobic Metabolism
  2. What are the four functions of Erythrocytes?
    • Gas Exchange
    • Acid-Base Balance -- Carbonic Anhydrase
    • Clear Immune Complexes
    • Clear Nitric Oxide
  3. Erythrocytes must maintain hemoglobin in a reduced state. How is this accomplished?
    They reduce methemoglobin (Fe3+) to hemoglobin (Fe2+)
  4. Erythrocytes must resist oxidant stress to protect themselves from the harmful effects of oxygen. How is this accomplished?
    They maintain Glutathione in its reduced state
  5. How many molecules of oxygen can each hemoglobin molecule carry? What molecule binds the oxygen?
    • 4
    • Iron
  6. What is the predominant hemoglobin in utero?
    Hgb F (Fetal Hemoglobin): α2 γ2
  7. When are normal adult levels of hemoglobin met?
    ~6 months
  8. On what chromosome is the alpha-gene cluster on? How many alphas are on each chromosome?
    • Chromosome 16
    • 2 alphas each for a total of 4
  9. On what chromosome is the beta-gene cluster on? How many betas are on each chromosome?
    • Chromosome 11
    • 1 beta per chromosome for a total of 2
  10. The ___________ structure of the hemoglobin molecule allows it to slide around, which alters the affinity of hemoglobin for oxygen. What is this measured as?
    • Quarternary
    • P50: partial pressure at which hemoglobin is 50% saturated with oxygen
  11. A DECREASED O2 affinity ____________ O2 unloading to tissues. This causes a ____________ shift in the O2 saturation curve, and a ___________ P50.
    What is this known as?
    • Increases
    • Rightward
    • Higher
    • Acidosis
  12. An INCREASED O2 affinity ______________ O2 unloading. This causes a ____________ shift in the O2 saturation curve, and a _________ P50.
    What is this known as?
    • Decreases
    • Leftward
    • Lower
    • Alkalosis
  13. What molecule regulates hemoglobin-oxygen affinity? This molecule decreases oxygen affinity by ___________ tissue oxygen supply. An increase in the concentration of this molecule causes a(n) _________ in affinity.
    • 2,3-diphosphoglycerate (2,3-DPG)
    • Increasing
    • Increase
  14. Does acidosis increase or decrease O2 affinity? What is this known as?
    • Decreases
    • Bohr Effect
  15. Does alkalosis increase or decrease O2 affinity?
  16. Does an increased temperature increase or decrease O2 affinity?
  17. What is the rate-limiting step of heme synthesis? On what chromosome is this enzyme located? What does it require? A deficiency in this enzyme can cause what two disease states?
    • ALA Synthetase
    • X Chromosome
    • Requires Pyridoxal 5'-phosphate
    • Sideroblastic Anemias & Inherited Porphyrias
  18. Normal Oxygenation of Hemoglobin:
    Oxyhemoglobin (Fe2+) --> Deoxyhemoglobin + O2
    (reverse reaction also occurs)
    What harmful products are formed from the spontaneous oxidation of Oxyhemoglobin?
    What enzyme catalyzes the reverse reaction, back to hemoglobin (thus protecting the RBC from harm)? What molecule is required for this reaction to take place, and where is it generated from?
    • Oxyhemoglobin --> Methemoglobin (Fe3+) + O2- (superoxide)
    • Methemoglobin Reductase
    • Requires NADH --> generated by glycolysis
  19. When Oxyhemoglobin (Fe2+) is spontaneously oxidized to methemoglobin and superoxide, what enzyme converts the superoxide to H2O2?
    H2O2 itself must then be reduced:
    2 GSH + H2O2 --> GSSG + 2 H2O

    What is GSH known as? What enzyme reduces GSSG back to GSH, to conserve the molecule? What molecule is needed for this reverse reaction, and where is it generated from?
    • Superoxide Dismutase
    • Glutathion (GSH) is "reducing back" for RBC -- protects them from harmful effects of superoxide ion by reducing it
    • Glutathione Reductase
    • Requires NADPH generated by hexose monophosphate shunt
  20. What pathway is responsible for producing 2,3-Diphosphoglycerate (2,3-DPG), which is the primary regulator of hemoglobin-O2 affinity?
    Rapoport-Luebering Pathway
  21. After approximately 120 days, most erythrocytes are trapped and phagocytosed by what system, and where is it located? This is an example of __________ hemolysis.
    • Reticuloendothelial System
    • Predominantly Spleen
    • Extravascular Hemolysis
  22. In extravascular hemolysis, hemoglobin dissociates into the globin protein and heme molecule. What is removed from the heme ring, and recycled back to marrow or stored within macrophage? The protoporphyrin ring is then opened. What does this result in?
    • Iron
    • Biliverdin & CO2
  23. In extravascular hemolysis, the protoporphyrin ring is opened, resulting in biliverdin and CO2. What is the biliverdin then converted to? This is known as unconjugated or "indirect". What conjugates it?
    An excess production of this molecule can result in a build-up of its unconjugated form. What can this result in?
    • Bilirubin
    • Liver
    • Increase in RBC breakdown
  24. In intravascular hemolysis (occurs in <10% of hemoglobin cells), the hemoglobin tetramer dissociates to what? What molecule do these then complex to, and what removes them from circulation?
    • alpha-beta dimers
    • Haptoglobin
    • Hepatocytes
  25. Excess hemoglobin in intravascular hemolysis may be phagocytosed by what cell type? They also may appear in urine as _______ __________ or ____________
    • Renal Tubular Cells
    • Free Hemoglobin or Methemoglobin
  26. How long is a RBC normally a reticulocyte?
    4 days: 3 in marrow, 1 in blood
  27. Reticulocytes are normally counted as % of RBCs. What is a normal reticulocyte count? How is this calculated?
    • ~0.5-2.5%
    • Ratio of reticulocytes to total RBCs X 100
  28. In anemia, the total RBC count is decreased. If the absolute reticulocyte count is unchanged, the ratio will _________ -- falsely suggesting _________ reticulocyte production. Therefore, the reticulocyte count must be corrected for this factor. How is this accomplished?
    • Increase
    • Increased
    • Corrected Reticulocyte Count: Patient retic count (%) X (Patient Hematocrit/ Normal Hematocrit)