Question 11

College Answer

Candidates generally provided detailed description of the cell lineage that led up to the  production of the mature red blood cell (RBC), but often omitted to mention those aspects unique to the RBC that were essential to its functions (e.g. biconcave shape gives the RBC a greater surface area and shorter distance to central regions, thus optimising diffusion of gases; the RBC enhanced ability to change shape and travel through narrow capillaries; lack of organelles maximises space for Hb, etc.). Mention of RBC function often lacked detail (e.g. restricted to just mentioning “O2 carriage”) or failed to mention, and describe, the RBC’s role in acid base buffering and HCO3- production.

Discussion

• Formation of red cells
  • Haematopoietic stem cells differentiate into myeloid stem cells
  • Myeloid progenitors differentiate into erythroid lineage (proerythroblasts)
  • Pro-erythroblasts synthesise haemoglobin until they lose their nucleus
  • Reticulocytes are enucleated; released into the circulation
  • Reticulocytes become erythrocytes when they lose their ribosome contents
• Structural features of red cells
  • 6-8 μm biconcave disks
  • 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)
• 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
• Fate of red cells
  • Lifespan = 120 days
  • 90% captured by the spleen and liver
  • 10% spontaneously haemolyse
  • Identified by the reticuloendothelial system as senescent because:
    • lose their deformability
    • express abnormal proteins on their surface
    • reversal of membrane phosphatidylserine 
    • coated in autologous anti-Band 3 IgG  (opsonin)
  • Degraded by macrophages
    • iron is reclaimed and returned to circulating transferrin, or stored in the macrophages

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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.

Yoshida, Hideyuki, et al. "Phosphatidylserine-dependent engulfment by macrophages of nuclei from erythroid precursor cells." Nature 437.7059 (2005): 754-758.

Bogdanova, Anna, and Hans U. Lutz. "Mechanisms tagging senescent red blood cells for clearance in healthy humans." Frontiers in physiology 4 (2013): 387.