Brain metabolism of 13N-ammonia during acute hepatic encephalopathy in cirrhosis measured by positron emission tomography.
Animal studies and results from 13N-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 13N-ammonia PET. Time courses were obtained of 13N-concentrations in cerebral cortex, basal ganglia, and cerebellum (PET-scans) as well as arterial 13N-ammonia, 13N-urea, and 13N-glutamine concentrations (blood samples) after 13N-ammonia injection. Regional 13N-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 13N-ammonia transfer across blood-brain barrier in cortex, PS(BBB), 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 13N-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 micromol/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.
Keiding
Susanne
S
Department of Medicine V (Hepatology), Aarhus University Hospital, Aarhus, Denmark. susanne@pet.auh.dk
Sørensen
Michael
M
Bender
Dirk
D
Munk
Ole Lajord
OL
Ott
Peter
P
Vilstrup
Hendrik
H
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000641:Ammonia / Q000378:metabolism*; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D005260:Female; D006501:Hepatic Encephalopathy / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009590:Nitrogen Radioisotopes; D049268:Positron-Emission Tomography
D009590:Nitrogen Radioisotopes; D000641:Ammonia