The brain in acute liver failure. A tortuous path from hyperammonemia to cerebral edema.
Acute liver failure (ALF) is a condition with an unfavourable prognosis. Multiorgan failure and circulatory collapse are frequent causes of death, but cerebral edema and intracranial hypertension (ICH) are also common complications with a high risk of fatal outcome. The underlying pathogenesis has been extensively studied and although the development of cerebral edema and ICH is of a complex and multifactorial nature, it is well established that ammonia plays a pivotal role. This review will focus on the effects of hyperammonemia on neurotransmission, mitochondrial function, oxidative stress, inflammation and regulation of cerebral blood flow. Finally, potential therapeutic targets and future perspectives are briefly discussed.
Bjerring
Peter Nissen
PN
Dept. Hepatology, section A-2121, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Eefsen
Martin
M
Hansen
Bent Adel
BA
Larsen
Fin Stolze
FS
D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology*; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D006501:Hepatic Encephalopathy / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D022124:Hyperammonemia / Q000150:complications*; D019586:Intracranial Hypertension / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D017114:Liver Failure, Acute / Q000150:complications*; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000502:physiology
D000641:Ammonia