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Brain metabolism of 13 N‐ammonia during acute hepatic encephalopathy in cirrhosis measured by positron emission tomography
Author(s) -
Keiding Susanne,
Sørensen Michael,
Bender Dirk,
Munk Ole Lajord,
Ott Peter,
Vilstrup Hendrik
Publication year - 2006
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21001
Subject(s) - hepatic encephalopathy , cirrhosis , glutamine , positron emission tomography , medicine , hyperammonemia , encephalopathy , ammonia , endocrinology , chemistry , pathology , nuclear medicine , biochemistry , amino acid
Animal studies and results from 13 N‐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 13 N‐ammonia PET. Time courses were obtained of 13 N‐concentrations in cerebral cortex, basal ganglia, and cerebellum (PET‐scans) as well as arterial 13 N‐ammonia, 13 N‐urea, and 13 N‐glutamine concentrations (blood samples) after 13 N‐ammonia injection. Regional 13 N‐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 13 N‐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 13 N‐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 μmol/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. (H EPATOLOGY 2005;43:42–50.)