Gut-derived ammonia is converted to urea by the liver; failure allows it to reach the brain
Expansion
Normal handling
- Colonic bacteria and enterocyte glutamine metabolism produce ammonia
- Absorbed into the portal vein and converted to urea by the liver’s urea cycle
- Muscle also removes ammonia by forming glutamine
In liver failure or portosystemic shunting, ammonia bypasses or overwhelms the liver and reaches the brain, where astrocytes convert it to glutamine. The osmotic effect causes astrocyte swelling and cerebral oedema, along with altered neurotransmission.
Precipitants are best remembered as anything that increases the nitrogen load or impairs clearance: gastrointestinal bleeding, constipation, infection, diuretics and electrolyte disturbance (especially hypokalaemia, which increases renal ammonia production), sedatives, dehydration, and a high protein load.
Treatment
- Lactulose: acidifies the colon so ammonia is trapped as non-absorbable ammonium, and speeds transit
- Rifaximin: a poorly absorbed antibiotic reducing ammonia-producing bacteria
- Treat the precipitant
Note that blood ammonia correlates poorly with the clinical grade, so it is not used to monitor treatment.