Precipitants of hepatic encephalopathy

Core concept3 exam ›

HE = ammonia + inflammation acting on an astrocyte
- Gut glutaminase and urease-producing flora generate NH3 from protein/urea
- Failing liver + portosystemic shunting -> NH3 bypasses urea cycle
- Astrocyte glutamine synthetase converts NH3 -> glutamine = osmolyte -> astrocyte swelling (Alzheimer type II change)
- -> inc GABAergic tone, dec glutamatergic transmission, cerebral oedema
Almost every episode has a precipitant - find it, don't just prescribe lactulose
Ammonia level correlates poorly with grade and should not be used to diagnose, grade or follow HE

Precipitants by mechanism

inc Nitrogen load
- GI bleed - blood is a protein meal (the classic); also causes hypovolaemia and dec renal clearance
- Constipation - inc colonic transit time -> inc absorption
- High protein load, azotaemia
Electrolyte / acid-base
- Hypokalaemia - the exam favourite. Two hits:
  - inc renal ammoniagenesis (K/H exchange -> intracellular acidosis in tubular cell -> inc glutamine metabolism)
  - coexisting alkalosis shifts NH4+ -> NH3, the un-ionised, lipid-soluble form that crosses the BBB
- Hyponatraemia, metabolic alkalosis, dehydration/over-diuresis
Infection - SBP, UTI, pneumonia; inflammation lowers the ammonia threshold
Drugs - benzodiazepines, opioids, alcohol, anticholinergics, PPIs (small-bowel bacterial overgrowth)
Shunting - TIPS, spontaneous portosystemic shunts, surgical shunt
Vascular/other - portal vein thrombosis, HCC, acute-on-chronic liver failure, renal failure

Grading (West Haven)

Grade	Features
Covert (minimal, I)	Psychometric abnormality only; trivial inattention, altered sleep
II	Lethargy, disorientation to time, asterixis, personality change
III	Somnolent but rousable, disorientation to place, gross confusion
IV	Coma, unresponsive to pain

Diagnosis of exclusion - always exclude hypoglycaemia, sepsis, subdural haematoma, Wernicke's, drug effect
Treat the precipitant - cultures + diagnostic paracentesis, stop diuretics, correct K and volume, treat bleeding
Lactulose first-line - colonic acidification traps NH4+, catharsis; titrate to 2-3 soft stools/day
- Enema/NG route if grade III-IV
Rifaximin added after a second episode -> reduces recurrence and hospitalisation
Protein restriction is obsolete and harmful - target 1.2-1.5 g/kg/day protein, favour vegetable and dairy sources, and give a late-evening snack
Persistent HE despite therapy -> image for large spontaneous portosystemic shunt (embolisable); consider transplant assessment
Consider ammonia-scavenging and urea cycle disorders / valproate toxicity where HE occurs without cirrhosis

Study aid only. These notes are written with the help of AI. Not for guiding clinical decisions.