Epidemiology

Etiology

Precipitating Factors
- Crucial for management steps (treat the trigger).
- GI Bleeding: $↑$ NH $_{3}$ production from breakdown of hemoglobin protein in gut.
- Infection (SBP, UTI, Pneumonia): $↑$ metabolic demand and catabolism.
- Constipation: $↑$ intestinal production/absorption of NH $_{3}$ .
- Hypokalemia/Alkalosis: Alkalosis facilitates NH $_{3}$ (uncharged) conversion from NH $_{4}^{+}$ (charged), allowing it to cross BBB. Hypokalemia promotes renal NH $_{3}$ production. c
- Drugs: Sedatives, narcotics, benzodiazepines (worsen GABAergic tone).
- TIPS Procedure: Shunts NH $_{3}$ -rich blood past liver directly to systemic circulation.

Liver failure $\to$ inability to detoxify nitrogenous waste $\to$ accumulation of neurotoxins (mainly Ammonia [NH $_{3}$ ]).
Ammonia hypothesis: NH $_{3}$ crosses blood-brain barrier $\to$ absorbed by astrocytes $\to$ converted to glutamine $\to$ osmotic stress and astrocyte swelling/cerebral edema.
$↓$ excitatory neurotransmission (glutamate) and $↑$ inhibitory neurotransmission (GABA).

Lactulose: a synthetic disaccharide laxative
- Indication: first-line for treatment of hepatic encephalopathy
- Mechanism: Lactulose is converted to lactic acid by intestinal flora → acidification in the gut → conversion of ammonia (NH3) to ammonium (NH4+) → ammonium is excreted in the feces → decreased blood ammonia concentration → decreased absorption of ammonia in the bowel → improved symptoms of hepatic encephalopathy
Rifaximin: a broad-spectrum, nonabsorbable oral antibiotic
- Reduces the number of ammonia-producing intestinal bacteria
- May be added to lactulose if a second episode occurs to prevent recurrent episodes of hepatic encephalopathy

tags	t1
aliases	Lactulose