Question 15

College Answer

The production and fate of red blood cells was well known to most candidates. Marrow 
production and its change with development, the sequence of haematogeny and RBC 
lifespan were well known. Some candidates failed to mention the role of erythropoietin and 
its stimulus by oxygen tension. The breakdown of haemoglobin caused much confusion. 
Globin (protein), Fe and haem (porphyrin ring) were all expected to be considered 
separately – many candidates omitted one or all. The steps were often confused as was the 
nature of transfer in blood, conjugation and release into bile. Conversion to stercobilinogen 
or urobilinogen (with reabsorption from the gut and excretion in urine) caused similar confusion. No marks were awarded for discussion of bile salt metabolism from cholesterol 
(not haem) or the differences between direct and indirect acting bilirubin.

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
• 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)
• Fate of haemoglobin
  • Free haemoglobin is bound to haptoglobin and captured by macrophages
  • Free haem is bound to haemopexin and captured by macrophages
  • Haemoglobin in senescent erythrocytes is reclaimed by macrophages
  • Inside reticuloendothelial macrophages:
    • Globin molecules are catabolised and released as amino acids
    • Haem is stripped of iron and converted into biliverdin, then bilirubin
      • Bilirubin circulated bound to albumin and is conjugated in the liver
      • Conjugated bilirubin is screted and converted into urobilinogen in the bowel, then into stercobilinogen and then into stercobilin
      • Urobilinogen can also be reabsorbed and exreted in the urine as urobilin
    • Iron is stored in the reticuloendothelial cells as ferritin or exported into the circulation, in which case it circulates as transferrin

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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.