Erythrocytes

Outline the physiological production of blood and its constituents

Erythrocytes:

• Are 7.5μm in diameter
• Are 2um thick
• Have a lifespan of 120 days
• Have:
  • No nucleus
    Maximises cell volume available for Hb.
  • No mitochondria
    Cannot perform aerobic metabolism - all ATP is generated via glycolysis.
  • No ribosomes Incapable of producing protein
• Have a biconcave disc shape
  This maximises surface area (optimising gas transfer) and makes the cells flexible enough to pass through capillary beds (which are narrower than the cell).
• Are important in:
  • Delivering O₂ to the tissues and delivering CO₂ to the lungs
  • Acid-Base balance
  • Metabolism of some drugs
• Carry ~29pg of haemoglobin
• Comprise 40-50% of blood volume

Production

Erythrocytes have a myeloid progenitor which differentiates into the myeloid line. EPO (see endocrine functions of the kidney stimulates myeloid progenitor cells to:

• Differentiate
• Proliferate

• Proerythroblasts begin synthesis of Hb, with ongoing production occurring until the cell is mature
• Further differentiation results in successive loss of organelles, increasing Hb content
• The loss of ribosomes and nucleus of the reticulocyte are the final stage of erythropoiesis
• The entire process takes ~7-10 days

Function

• Gas Carriage
• Acid-Base Buffering
  • Production of HCO₃^-
  • Binding of H⁺ to Hb
• Metabolism
  Esterases (and other -ases) in erythrocytes metabolise many drugs, including:
  • Remifentanil
  • SNP (reacts with Hb to form NO, CN, and Met-Hb)
  • Esmolol

Elimination

Old red cells are removed from circulation via:

• Phagocytosis by macrophages in:
  • Spleen
    Major mechanism.
  • Liver
  • Bone marrow
• Haemolysis
  ~10% of red cell breakdown occurs in circulation, where the Hb dimers are then bound to haptoglobin by haemopexin.
  • This is important to prevent glomerular filtration of haeme, and loss of iron

Haemoglobin Metabolism

Haemoglobin is broken down into:

• Globin
  Broken down into constituent amino acids.
• Iron
  Re-enters haemoglobin synthetic pathway.
• Haeme
  Complex metabolic pathway, notable as it is the only metabolic process that produces carbon monoxide:
  • Metabolised to biliverdin by splenic macrophages in the reticuloendothelial system of the spleen
    • Circulating erythrocytes are phagocytosed by splenic macrophages
    • Haptoglobin binds circulating Hb, the Hb-Haptoglobin complex is then phagocytosed by splenic macrophages
  • Biliverdin is reduced to unconjugated bilirubin
    This is fat soluble, and binds to albumin.
  • Unconjugated bilirubin is conjugated in the liver to conjugated bilirubin
  • Conjugated bilirubin is secreted in bile by active transport
    This is impaired during hepatic disease, leading to increased bilirubin levels in plasma.
  • Secreted conjugated bilirubin is metabolised to urobilinogen by gut bacteria
  • Urobilinogen may have a number of fates:
    • Enterohepatic recirculation and elimination in bile (again)
    • Further metabolism by gut bacteria to stercobilinogen and then to stercobilin
    • Enterohepatic recirculation and urinary excretion, where it is oxidised to urobilin

In Disease

References

1. Barrett KE, Barman SM, Boitano S, Brooks HL. Ganong's Review of Medical Physiology. 24th Ed. McGraw Hill. 2012.