Question 14

College Answer

This question was best answered by considering form and then function. Detailing red cell  size, that it is a biconcave disc, contains haemoglobin A (Hb F in-utero), has a central Fe moiety and demonstrates positive cooperativity in binding oxygen would be a good start. Additionally, noting that the RBC has a flexible membrane with shape maintained by structural proteins and that it lacks a nucleus, organelles and mitochondria, but contains carbonic  anhydrase would pass this question. A complete answer would mention the3 shunts that come off the anaerobic glycolytic pathway  (RBC’s only means of ATP generation), namely the production of 2-3 DPG  via the RapoportLuebering shunt, generation of NADPH by the hexose monophosphate shunt (protects RBC from oxidative damage) and the reduction of metHb back to Hb by way of the NADH. Many answers lacked sufficient information to pass this question. Many answers included lengthy discussions about the production of RBC’s, the Oxyhaemoglobin dissociation curve or calculated the oxygen content of blood. RBC metabolic adaptations (e.g. 2, 3-DPG, NADPH production by the HMP shunt/ G6phosphatase to regenerate glutathione and metHb reductase) were rarely mentioned, as were vasodilatory mediators released by RBCs.

Discussion

The college answer brought out a lot of RBC features which, though interesting, are only tenuously connected to the functions of the red cell which "facilitate oxygen transport". It appears the examiners wanted the candidates to answer the question, "what are the metabolic, structural and functional features of red cells?" Thus:

• Structural features of red cells
  • 6-8 μm biconcave disks; this shape is optimal because
    • Maximal surface to volume ratio
    • Minimal diffusion distance from the cell centre
    • Enhanced deformability, particularly adapted to paraboloidal transformation in capillaries
    • Maximised laminar flow (less prone to rotation during flow in the large vessels) which discourages atherogenesis
  • Beneficial ultrastructural features:
    • Extremely negative surface charge (prevents clumping agglutination)
    • Dynamic cytoskeleton (permits repeated reversible deformability)
    • Lack of nucleus (maximises deformability)
    • Lack of organelles (maximises space for haemoglobin)
  • Main intracellular content is haemoglobin (330g/L)
• Metabolism of red cells
  • The glycolytic (Embden-Meyerhof) pathway: main mechanism of ATP synthesis which also generates NADH
  • Methaemoglobin reductase pathway borrows this NADH to reduce methaemoglobin back to haemoglobin 
  • The Luebering-Rapaport shunt produces 2,3-diphosphoglycerate (2,3-DPG) by borrowing 1,3 diphosphoglycerate from the pathway before it can be converted to pyruvate.
  • The hexose monophosphate shunt produces NADPH, which then converts oxidised glutathione to reduced glutathione, and this is used as an antioxidant to protect the RBC membrane and enzymes.
• Function of red cells
  • Oxygen transport
  • Packaged form of haemoglobin (protects from haemoglobin toxicity)
  • Protein buffering (by haemoglobin histidine residues)
  • Bicarbonate buffering (synthesis of bicarbonate by carbonic anhydrase)
  • Mitigation of pH change in the peripheral circulation by Hamburger effect
  • Inhibitory control of complement
  • Regional blood flow autoregulation via nitric oxide/nitrite balance

Gordon-Smith, Ted. "Structure and function of red and white blood cells." Medicine 41.4 (2013): 193-199.

Diez-Silva, Monica, et al. "Shape and biomechanical characteristics of human red blood cells in health and disease." MRS bulletin 35.5 (2010): 382-388.

Snyder, Gregory K., and Brandon A. Sheafor. "Red blood cells: centerpiece in the evolution of the vertebrate circulatory system." American zoologist 39.2 (1999): 189-198.