Hyperammonaemia in cirrhotics is managed with lactulose and rifaximin. At the molecular level, how does lactulose reduce blood ammonia?
- A Lactulose is metabolised by colonic bacteria to short-chain fatty acids that acidify the colon, converting NH3 to NH4+ (which cannot be absorbed) and promoting ammonia excretion in stool ✓
- B Lactulose directly binds and inactivates urease in colonic bacteria
- C Lactulose stimulates hepatic urea cycle enzymes to increase ammonia clearance
- D Lactulose acts as an osmotic cathartic, excreting protein before bacterial degradation
Explanation
Lactulose (galactose-fructose disaccharide) is not digested in the small intestine; in the colon, bacteria ferment it to acetic, lactic, and propionic acids, lowering colonic pH below 6. At this pH, luminal NH3 is protonated to NH4+ (pKa 9.25 favours NH4+ at acidic pH), which is lipid-insoluble and cannot cross colonocyte membranes. This traps ammonia in the lumen and promotes its excretion in stool. The osmotic effect accelerates transit, also limiting time for bacterial ammonia production. Rifaximin reduces the urease-producing bacterial load. Lactulose does not directly inhibit urease or stimulate hepatic urea cycle enzymes.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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