title: Cerebral ammonia metabolism in patients with severe liver disease and minimal hepatic encephalopathy.
abstract: Cerebral ammonia metabolism was studied in five control subjects and five patients with severe liver disease exhibiting minimal hepatic encephalopathy. The arterial ammonia concentration in the control subjects was 30 +/- 7 mumol/L (mean +/- SD) and 55 +/- 13 mumol/L in the patients (p less than 0.01). In the normal subjects, the whole-brain values for cerebral blood flow, cerebral metabolic rate for ammonia, and the permeability-surface area product for ammonia were 0.58 +/- 0.12 ml g-1 min-1 0.35 +/- 0.15 mumol 100 g-1 min-1, and 0.13 +/- 0.03 ml g-1 min-1, respectively. In the patients, the respective values were 0.46 +/- 0.16 ml g-1 min-1 (not different from control), 0.91 +/- 0.36 mumol 100 g-1 min-1 (p less than 0.025), and 0.22 +/- 0.07 ml g-1 min-1 (p less than 0.05). The increased permeability-surface area product of the blood-brain barrier permits ammonia to diffuse across the blood-brain barrier into the brain more freely than normal. This may cause ammonia-induced encephalopathy even though arterial ammonia levels are normal or near normal and explain the emergence of toxin hypersensitivity as liver disease progresses. Greater emphasis on early detection of encephalopathy and aggressive treatment of minimal hyperammonemia may retard the development of ammonia-induced complications of severe liver disease.
authors.affiliation: Department of Neurology, University of Texas School of Medicine, Houston 77030.
authors.forename: A H
authors.initials: AH
authors.lastname: Lockwood
authors.forename: E W
authors.initials: EW
authors.lastname: Yap
authors.forename: W H
authors.initials: WH
authors.lastname: Wong
mesh_terms: D000328:Adult; D000641:Ammonia / Q000378:metabolism*; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D005260:Female; D006501:Hepatic Encephalopathy / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007700:Kinetics; D008107:Liver Diseases / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged
chemical_list: D000641:Ammonia