Brain metabolism of 13N-ammonia during acute hepatic encephalopathy in cirrhosis measured by positron emission tomography

Animal studies and results from N-13-ammonia positron emission tomography (PET) in patients with cirrhosis and minimal hepatic encephalopathy suggest that a disturbed brain ammonia metabolism plays a pivotal role in the pathogenesis of hepatic encephalopathy (HE). We studied brain ammonia kinetics in 8 patients with cirrhosis with an acute episode of clinically overt HE (I-IV), 7 patients with cirrhosis without HE, and 5 healthy subjects, using contemporary dynamic N-13-ammonia PET. Time courses were obtained of N-13-concentrations in cerebral cortex, basal ganglia, and cerebellum (PET-scans) as well as arterial N-13-ammonia, N-13-urea, and N-13-glutamine concentrations (blood samples) after N-13-ammonia injection. Regional N-13-ammonia kinetics was calculated by non-linear fitting of a physiological model of brain ammonia metabolism to the data. Mean permeability-surface area product of N-13-ammonia transfer across blood-brain barrier in cortex, PSBBB, was 0.21 mL blood/min/mL tissue in patients with HE, 0.31 in patients without HE, and 0.34 in healthy controls; similar differences were seen in basal ganglia and cerebellum. Metabolic trapping of blood N-13-ammonia in the brain showed neither regional, nor patient group differences. Mean net metabolic flux of ammonia from blood into intracellular glutamine in the cortex was 13.4 mu mol/min/L tissue in patients with cirrhosis with HE, 7.4 in patients without HE, and 2.6 in healthy controls, significantly correlated to blood ammonia. In conclusion, increased cerebral trapping of ammonia in patients with cirrhosis with acute HE was primarily attributable to increased blood ammonia and to a minor extent to changed ammonia kinetics in the brain.