Pathogenesis of Hepatic Encephalopathy in Acute Liver Failure

Vaquero, Javier; Chung, Chuhan; Cahill, Michael E.; Blei, Andrés T.

doi:10.1055/s-2003-42644

Cited by 137 publications

(14 citation statements)

References 103 publications

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“…Gastrointestinal bleeding, excessive protein intake and constipation increase ammonia due to the higher absorption of nitrogenous compounds from the gut and renal failure or hydroelectrolytic abnormalities, often due to diuretics, provoke increased renal ammonia production or reabsorption. In fact, in the recent years a new view of the pathophysiology of HE takes four organs into account in which the traffic of ammonia may result in increases of this substance in the brain: the liver, the gut, the kidney and the muscle [18]. In cases of HE induced by the intake of benzodiazepines, it is obvious that this compound plays a major causative role.…”

Section: The Pathophysiological Basis Of He Therapymentioning

confidence: 99%

“…2) [24]. Since the pathophysiological and clinical value of these therapies are discussed elsewhere, the most important aspect to stress here is the fact that a restrictive protein diet worsens the nutritional status of the patients, does not improve the outcome of HE and can actually lead to an increase in ammonia due to reduction in the muscular removal of this substance [18]. In this connection, a recent study has shown that a normoproteic diet can be safely administered to patients with acute HE (fig.…”

Section: The Pathophysiological Basis Of He Therapymentioning

confidence: 99%

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Hepatic Encephalopathy: From Pathophysiology to Treatment

Mas¹

2006

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Hepatic encephalopathy (HE) is a neuropsychiatric syndrome due to hepatic dysfunction and porto-systemic shunting of the intestinal blood. Cirrhosis is the most frequent liver disease causing HE. On most occasions, HE appears due to a superimposed precipitating factor (gastrointestinal bleeding, infections, renal and electrolyte disturbances, etc.). Ammonia produced in colon by intestinal bacteria is the main toxic substance implicated in the pathogenesis of HE. Other mechanisms, such as changes in the GABA-benzodiazepine system, accumulation of manganese into the basal ganglia of the brain, changes in blood-brain barrier and neurotransmission disturbances are also present. Clinical manifestations of HE may vary widely, from minimal neurologic changes, only detected with specific tests, to deep coma. Treatment of HE should be directed to controlling the precipitating factors, as well as therapies aimed at correcting the above-mentioned pathophysiological changes, mainly reduction of blood ammonia levels. Artificial liver support systems may play a role in the future. Liver transplantation should be evaluated as a definitive therapy in all cases of HE.

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Section: The Pathophysiological Basis Of He Therapymentioning

confidence: 99%

Section: The Pathophysiological Basis Of He Therapymentioning

confidence: 99%

Hepatic Encephalopathy: From Pathophysiology to Treatment

Mas¹

2006

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“…This high mortality is in part due to the development of severe brain edema that leads to increased intracranial pressure and brain herniation. Currently, there is no effective treatment for the brain edema in ALF other than emergency liver transplantation (2–4). …”

Section: Introductionmentioning

confidence: 99%

Brain Aquaporin-4 in Experimental Acute Liver Failure

Rao

Jayakumar

Tong

et al. 2010

J Neuropathol Exp Neurol

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Intracranial hypertension due to brain edema and associated astrocyte swelling is a potentially lethal complication of acute liver failure (ALF). Mechanisms of edema formation are not well understood but elevated levels of blood and brain ammonia and its byproduct glutamine have been implicated in this process. We examined mRNA and protein expression of the water channel protein aquaporin-4 (AQP4) in cerebral cortex in a rat model of ALF induced by the hepatotoxin thioacetamide. Rats with ALF showed increased AQP4 protein in the plasma membrane (PM). Total tissue levels of AQP4 protein and mRNA levels were not altered indicating that increased AQP4 is not transcriptionally mediated but is likely due to a conformational change in the protein, i.e. a more stable anchoring of AQP4 to the PM and/or interference with its degradation. By immunohistochemistry there was an increase in AQP4 immunoreactivity in the PM of perivascular astrocytes in ALF. Rats with ALF showed increased levels of α-syntrophin, a protein involved in the anchoring of AQP4 to perivascular astrocytic end-feet. Increased AQP4 and α-syntrophin levels were inhibited by L-histidine, an inhibitor of glutamine transport into mitochondria, suggesting a role for glutamine in the increase of PM levels of AQP4. These results indicate that increased AQP4 PM levels in perivascular astrocytic end-feet are likely critical to the development of brain edema in ALF.

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“…[119] Since severe liver pathology, such as liver failure or hepatitis C infection, is associated with encephalitis and cognitive decline,[209] it is easy to imagine that chronic liver disease induced by aluminum could contribute to impaired ability to recover from brain trauma, even in children and young adults.…”

Section: Aluminum Work Synergistically With Glyphosatementioning

confidence: 99%

Diminished brain resilience syndrome: A modern day neurological pathology of increased susceptibility to mild brain trauma, concussion, and downstream neurodegeneration

Morley¹,

Seneff²

2014

Surg Neurol Int

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The number of sports-related concussions has been steadily rising in recent years. Diminished brain resilience syndrome is a term coined by the lead author to describe a particular physiological state of nutrient functional deficiency and disrupted homeostatic mechanisms leading to increased susceptibility to previously considered innocuous concussion. We discuss how modern day environmental toxicant exposure, along with major changes in our food supply and lifestyle practices, profoundly reduce the bioavailability of neuro-critical nutrients such that the normal processes of homeostatic balance and resilience are no longer functional. Their diminished capacity triggers physiological and biochemical ‘work around’ processes that result in undesirable downstream consequences. Exposure to certain environmental chemicals, particularly glyphosate, the active ingredient in the herbicide, Roundup®, may disrupt the body's innate switching mechanism, which normally turns off the immune response to brain injury once danger has been removed. Deficiencies in serotonin, due to disruption of the shikimate pathway, may lead to impaired melatonin supply, which reduces the resiliency of the brain through reduced antioxidant capacity and alterations in the cerebrospinal fluid, reducing critical protective buffering mechanisms in impact trauma. Depletion of certain rare minerals, overuse of sunscreen and/or overprotection from sun exposure, as well as overindulgence in heavily processed, nutrient deficient foods, further compromise the brain's resilience. Modifications to lifestyle practices, if widely implemented, could significantly reduce this trend of neurological damage.

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Pathogenesis of Hepatic Encephalopathy in Acute Liver Failure

Cited by 137 publications

References 103 publications

Hepatic Encephalopathy: From Pathophysiology to Treatment

Hepatic Encephalopathy: From Pathophysiology to Treatment

Brain Aquaporin-4 in Experimental Acute Liver Failure

Diminished brain resilience syndrome: A modern day neurological pathology of increased susceptibility to mild brain trauma, concussion, and downstream neurodegeneration

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