How is hepatic metabolism of ammonia affected by changes in pH?

  • The liver can metabolise ammonia (NH3) via three pathways
  • The degree to which each pathway is used depends upon pH and the need for bicarbonate to be preserved or produced:
Urea Production
(Ureagenesis)
  • Upstream hepatocytes convert ammonia to urea through the ‘urea cycle'
  • Urea is then excreted unchanged by the kidneys
  • Forms the main pathway of nitrogen excretion
  • Pathway inhibited by acidosis
Glutamine Production
  • Downstream hepatocytes convert ammonia into glutamine
  • Can be used by the kidneys to generate NH4+ resulting in an alkalinising effect
  • Facilitates the excretion of Cl-
  • Usually represents a lesser pathway
  • Upregulated in acidosis:
    • More ammonia available to downstream hepatocytes due to inhibition of ureagenesis
    • Production of glutamine independently stimulated