Medical Therapy of Brain Edema in Fulminant Hepatic Failure

Blei, M.D. Andres T.

doi:10.1053/jhep.2000.17923

Cited by 37 publications

(22 citation statements)

References 46 publications

(43 reference statements)

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“…The patients with acute liver failure experience asterexis, hyperflexia, cortical blindness, retarded speech, seizures, brain edema and coma. The death in these cases is more often due to cerebral edema as a result of increased intracranial pressure and brain herniation [9,10]. In hepatic failure surveillance study, a very poor survival rate was observed in these patients.…”

Section: Introductionmentioning

confidence: 99%

Thioacetamide-Induced Fulminant Hepatic Failure Induces Cerebral Mitochondrial Dysfunction by Altering the Electron Transport Chain Complexes

et al. 2011

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Fulminant hepatic failure (FHF) is an acute form of hepatic encephalopathy resulting from severe inflammatory or necrotic liver damage without any previously established liver damage. This develops as a complication due to viral infections, and drug abuse. FHF also occurs in acute disorders like Reye's syndrome. Although the exact mechanisms in the etiology of FHF are not understood, elevated levels of brain ammonia have been consistently reported. Such increased ammonia levels are suggested to alter neurotransmission signals and impair cerebral energy metabolism due to mitochondrial dysfunctions. In the present study we have examined the role of cerebral electron transport chain complexes, including complex I, II, III IV, and pyruvate dehydrogenase in the non-synaptic mitochondria isolated from the cortex of the thioacetamide-induced FHF rats. Further, we have examined if the structure of mitochondria is altered. The results of the current study demonstrated a decrease in the activity of the complex I by 31 and 48% at 18 and 24 h respectively after the thioacetamide injection. Similarly, the activity of electron transport chain complex III was inhibited by 35 and 52% respectively, at 18 and 24 h, respectively. The complex II and complex IV, on the other hand, revealed unaltered activity. Further the activity of pyruvate dehydrogenase at 18 and 24 h after the induction of FHF was inhibited by 29 and 43%, respectively. Our results also suggest mitochondrial swelling in FHF induced rats. The inhibition of the respiratory complexes III and I and pyruvate dehydrogenase might lead to the increased production of free radical resulting in oxidative stress and cerebral energy disturbances thereby leading to mitochondrial swelling and further contributing to the pathogenesis of FHF.

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Section: Introductionmentioning

confidence: 99%

Thioacetamide-Induced Fulminant Hepatic Failure Induces Cerebral Mitochondrial Dysfunction by Altering the Electron Transport Chain Complexes

et al. 2011

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“…Historically, cerebral edema was believed to develop in up to 80% of patients with ALF and be the most common cause of death. 3 However, recent data following a review of 3300 patients presenting to a single tertiary liver center has shown that the proportion of patients with intracranial hypertension (ICH) fell from 76% in 1984-88 to 20% in 2004-08 (P < 0.0001). In those who developed ICH, mortality fell from 95% to 55% (P < 0.0001).…”

mentioning

confidence: 99%

Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

Aldridge

Tranah

Shawcross

2015

Journal of Clinical and Experimental Hepatology

237

190

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The syndrome we refer to as Hepatic Encephalopathy (HE) was first characterized by a team of Nobel Prize winning physiologists led by Pavlov and Nencki at the Imperial Institute of Experimental Medicine in Russia in the 1890's. This focused upon the key observation that performing a portocaval shunt, which bypassed nitrogen-rich blood away from the liver, induced elevated blood and brain ammonia concentrations in association with profound neurobehavioral changes. There exists however a spectrum of metabolic encephalopathies attributable to a variety (or even absence) of liver hepatocellular dysfunctions and it is this spectrum rather than a single disease entity that has come to be defined as HE. Differences in the underlying pathophysiology, treatment responses and outcomes can therefore be highly variable between acute and chronic HE. The term also fails to articulate quite how systemic the syndrome of HE can be and how it can be influenced by the gastrointestinal, renal, nervous, or immune systems without any change in background liver function. The pathogenesis of HE therefore encapsulates a complex network of interdependent organ systems which as yet remain poorly characterized. There is nonetheless a growing recognition that there is a complex but influential synergistic relationship between ammonia, inflammation (sterile and non-sterile) and oxidative stress in the pathogenesis HE which develops in an environment of functional immunoparesis in patients with liver dysfunction. Therapeutic strategies are thus moving further away from the traditional specialty of hepatology and more towards novel immune and inflammatory targets which will be discussed in this review. ( J CLIN EXP HEPATOL 2015;5:S7-S20) H epatic encephalopathy (HE) is the term used to encapsulate the broad spectrum of neuropsychiatric disturbances associated with both acute and chronic liver failure (ALF and CLF, respectively), as well as porto-systemic bypass in the absence of hepatocellular disease. The clinical manifestations of HE can be extremely heterogeneous in nature, with symptoms presenting anywhere on a continuum spanning from seemingly normal cognitive performance, right the way through to states of confusion, stupor and coma. In between these extremes, patients with HE may exhibit signs such as inattentiveness, blunted affect, impairment of memory or reversal of the sleep-wake cycle, as well as physical manifestations such as tremor, myoclonus, asterixis and deep tendon hyperreflexia.ALF is defined by the onset of coagulopathy alongside any degree of encephalopathy in patients with no evidence of pre-existing liver disease. 1 The presence of HE in those with ALF is prognostic, with up to a quarter of cases developing raised intracranial pressure. 2 Patients presenting with ALF are at risk of developing its cardinal, lifethreatening feature, cerebral edema. Left untreated, cerebral edema can rapidly progress to cause herniation of the uncus through the falx cerebri, leading to compression of the brainstem and, ultimately, death. H...

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“…12 However, recent data suggests that only about 20-25% cases of ALF have ICH. Among the patients who develop ICH, mortality rates are found to be much lesser.…”

Section: Correct Answers: D and Ementioning

confidence: 99%