Hepatic encephalopathy

Epidemiology

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Etiology

• Precipitating Factors
  • Crucial for management steps (treat the trigger).
  • GI Bleeding: $\uparrow$ NH${}_3$ production from breakdown of hemoglobin protein in gut.
  • Infection (SBP, UTI, Pneumonia): $\uparrow$ metabolic demand and catabolism.
  • Constipation: $\uparrow$ 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.
  • Drugs: Sedatives, narcotics, benzodiazepines (worsen GABAergic tone).
  • TIPS Procedure: Shunts NH${}_3$-rich blood past liver directly to systemic circulation.

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Pathophysiology

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• 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.
• $\downarrow$ excitatory neurotransmission (glutamate) and $\uparrow$ inhibitory neurotransmission (GABA).

Clinical features

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Diagnostics

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Treatment

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• 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