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 endorcrine 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 ciruclation, 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 sterobilin
      • Enterohepatic recirculation and urinary excretion, where it is oxidised to urobilin

In Disease

Blood Urine Faeces
Prehepatic disease ↑ Unconjugated bilirubin ↑ Urobilinogen, bilirubin not present Normal
Intrahepatic disease ↑ Conjugated bilirubin, ↑ Unconjugated bilirubin Bilirubin present May be pale due to decreased urobilinogen excreted in bile
Posthepatic disease ↑ Conjugated bilirubin ↓ Urobilinogen, bilirubin present Pale

References

  1. Barrett KE, Barman SM, Boitano S, Brooks HL. Ganong's Review of Medical Physiology. 24th Ed. McGraw Hill. 2012.
Last updated 2017-09-17

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