Handling of ammonia

Vivian Imbriotis | June 21, 2026

Ammonia is

  • the major product of protein and nucleotide catabolism
  • in equilibrium \(NH_3 + H^+ \leftrightharpoons NH_4^+\) with pKa 9 (\(\therefore\) almost all ionized at physiologic pH)
  • <35\(\mu\)M in serum

Ammonia sources

  • Purine catabolism
  • Amino acid catabolism
  • Renal ammoniogenesis from glutamine (allows for ammonium excretion \(\to\) chloride excretion \(\to\) body alkalinization)
  • Bacterial urease (see below)

All circulating ammonia

  • Is delivered to the liver where it enters urea cycle \(2NH_3 + CO_2 \to \text{Urea} + H_2O\)

Then urea is 75% excreted renally

  • Freely filtered at glomerulus
  • 50% reabsorbed in PCT
  • Equal amount then actively secreted in LoH
  • Reabsorption in medullary collecting duct is \(\propto\) ADH level
  • About 50% of filtered load is excreted

And 25% excreted in stool

  • Bacterial urease cleaves urea \(\to 2NH_3 + CO_2\)
  • Some ammonia \(\to\) faeces
  • Remainder diffuses back to blood (enterohepatic re-circulation)


Lactulose

  • Nonabsorbable synthetic disaccharide
  • Dose 20mg BD \(\to\) QID
  • Acts as an osmotic laxative
  • Metabolized in colon by coliforms to lactic and acetic acids \(to \ \downarrow\)colonic pH
  • Acidic environment limits bacterial overgrowth \(\to\) fewer coliforms \(\to\) less urease presence \(\to\) decreased cleavage of urea to ammonia
  • Ion traps ammonia as ammonium \(\to\) larger proportion lost in faeces rather than enterohepatically cycled

Rifaximin

  • Nonabsorbable rifamicin antibiotic (inhibits bacterial RNA polymerase \(\to\) bacteriostatic)
  • Retained in gut by active p-glycoprotein efflux (inhibitors e.g. cyclosporin, amiodarone will increase systemic exposure)
  • \(\downarrow\) coliform bacteria \(\to\) less urease presence \(\to\) decreased cleavage of urea to ammonia