Increase brain lactate in hepatic encephalopathy: Cause or consequence?

Rose, Christopher F.

doi:10.1016/j.neuint.2010.06.012

Cited by 20 publications

(17 citation statements)

References 98 publications

(100 reference statements)

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“…27 Cerebral metabolites such as lactate have been found to be increased in animal models 8,21 and in cerebrospinal fluid from patients with HE, 22 which may indicate increased glycolysis, but whether increased lactate is a cause or consequence of HE is uncertain. 23 Thus, although we were unable to link the decrease in CMRO 2 to an increase in CMRA, we cannot rule out that ammonia may be involved in the pathogenesis of HE, perhaps through subtle effects on energy metabolism. This is supported by the higher blood levels of ammonia and CMRA in the patients after recovery from HE compared to the control patients.…”

Section: Discussionmentioning

confidence: 85%

Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake

et al. 2013

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Studies have shown decreased cerebral oxygen metabolism (CMRO 2 ) and blood flow (CBF) in patients with cirrhosis with hepatic encephalopathy (HE). It remains unclear, however, whether these disturbances are associated with HE or with cirrhosis itself and how they may relate to arterial blood ammonia concentration and cerebral metabolic rate of blood ammonia (CMRA). We addressed these questions in a paired study design by investigating patients with cirrhosis during and after recovery from an acute episode of HE type C. CMRO 2 , CBF, and CMRA were measured by dynamic positron emission tomography (PET)/computed tomography (CT). Ten patients with cirrhosis were studied during an acute episode of HE; nine were reexamined after recovery. Nine patients with cirrhosis with no history of HE served as controls. Mean CMRO 2 increased from 0.73 lmol oxygen/mL brain tissue/min during HE to 0.91 lmol oxygen/mL brain tissue/min after recovery (paired t test; P < 0.05). Mean CBF increased from 0.28 mL blood/mL brain tissue/min during HE to 0.38 mL blood/mL brain tissue/min after recovery (P < 0.05). After recovery from HE, CMRO 2 and CBF were not significantly different from values in the control patients. Arterial blood ammonia concentration decreased 20% after recovery (P < 0.05) and CMRA was unchanged (P > 0.30); both values were higher than in the control patients (both P < 0.05). Conclusion: The low values of CMRO 2 and CBF observed during HE increased after recovery from HE and were thus associated with HE rather than the liver disease as such. The changes in CMRO 2 and CBF could not be linked to blood ammonia concentration or CMRA. (HEPATOLOGY 2013;57:258-265) B rain energy metabolism is believed to be disturbed in patients with cirrhosis with hepatic encephalopathy (HE).1 Studies have shown decreased cerebral oxygen consumption (CMRO 2 ) and blood flow (CBF) in patients with cirrhosis and HE when compared to patients with cirrhosis without HE or healthy subjects, whereas the latter two groups of subjects had similar values.2-5 Cross-sectional studies point to the reductions being related to the HE condition and not to the liver disease itself. 4,5 In accordance with this, one study reported that reductions in CMRO 2 and CBF were restored when patients, treated with a dopamine agonist, recovered from HE.3 Another study, however, found decreased CMRO 2 but unchanged CBF in patients with a history of HE when compared to patients without a history of HE or healthy controls.6 It thus remains an open question whether the reductions in CMRO 2 and CBF in patients with cirrhosis and HE normalize after recovery from HE, and in the present study we therefore measured CMRO 2 and CBF during and after recovery from an episode of HE in individual patients with cirrhosis.Another key question is how changes in CMRO 2 and CBF may relate to the blood concentration of ammonia. Patients with cirrhosis with HE usually have higher Abbreviations: CBF, cerebral blood flow; CMRA, cerebral metabolic rate of blood ammonia; CMRO 2 , cerebral o...

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Section: Discussionmentioning

confidence: 85%

Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake

et al. 2013

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“…In animal models of and patients with ALF, an increase in brain lactate concentration has been reported . Concentrations of lactate in the cerebrospinal fluid were also found to be elevated in patients with cirrhosis, but only in severe cases of HE .…”

Section: Discussionmentioning

confidence: 95%

Ammonia mediates cortical hemichannel dysfunction in rodent models of chronic liver disease

et al. 2017

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The pathogenesis of hepatic encephalopathy (HE) in cirrhosis is multifactorial and ammonia is thought to play a key role. Astroglial dysfunction is known to be present in HE. Astrocytes are extensively connected by gap junctions formed of connexins, which also exist as functional hemichannels allowing exchange of molecules between the cytoplasm and the extracellular milieu. The astrocyte‐neuron lactate shuttle hypothesis suggests that neuronal activity is fueled (at least in part) by lactate provided by neighboring astrocytes. We hypothesized that in HE, astroglial dysfunction could impair metabolic communication between astrocytes and neurons. In this study, we determined whether hyperammonemia leads to hemichannel dysfunction and impairs lactate transport in the cerebral cortex using rat models of HE (bile duct ligation [BDL] and induced hyperammonemia) and also evaluated the effect of ammonia‐lowering treatment (ornithine phenylacetate [OP]). Plasma ammonia concentration in BDL rats was significantly reduced by OP treatment. Biosensor recordings demonstrated that HE is associated with a significant reduction in both tonic and hypoxia‐induced lactate release in the cerebral cortex, which was normalized by OP treatment. Cortical dye loading experiments revealed hemichannel dysfunction in HE with improvement following OP treatment, while the expression of key connexins was unaffected. Conclusion: The results of the present study demonstrate that HE is associated with central nervous system hemichannel dysfunction, with ammonia playing a key role. The data provide evidence of a potential neuronal energy deficit due to impaired hemichannel‐mediated lactate transport between astrocytes and neurons as a possible mechanism underlying pathogenesis of HE. (Hepatology 2017;65:1306‐1318)

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“…For example, following hypo-osmotic stress in normal mice, water entry was evidenced only in astrocytes and not in neurons (Nase et al, 2008), suggesting that neurons are more effective in preserving their volume in abnormal osmotic conditions. This difference can be explained by dissimilar metabolic and transport characteristics of the two types of cells, including osmotic gradients and ionic fluxes through membrane channels (Kelly andRose, 2010 andOlson and.…”

Section: Astrocyte Swelling and Brain Edema In Liver Disease/failurementioning

confidence: 99%

“…Lactate is another pathogenic factor involved in the development of HE (Rose, 2010). It is important to note that lactate is no longer considered only a product of anaerobic glycolysis but is also a metabolite used by neurons as an energetic substrate (Pellerin and Magistretti, 2011).…”

Section: Lactatementioning

confidence: 99%

Brain edema in acute liver failure and chronic liver disease: Similarities and differences

Bosoi

Rose

2013

Neurochemistry International

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Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that typically develops as a result of acute liver failure or chronic liver disease. Brain edema is a common feature associated with HE. In acute liver failure, brain edema contributes to an increase in intracranial pressure, which can fatally lead to brain stem herniation. In chronic liver disease, intracranial hypertension is rarely observed, even though brain edema may be present. This discrepancy in the development of intracranial hypertension in acute liver failure versus chronic liver disease suggests that brain edema plays a different role in relation to the onset of HE. Furthermore, the pathophysiological mechanisms involved in the development of brain edema in acute liver failure and chronic liver disease are dissimilar. This review explores the types of brain edema, the cells, and pathogenic factors involved in its development, while emphasizing the differences in acute liver failure versus chronic liver disease. The implications of brain edema developing as a neuropathological consequence of HE, or as a cause of HE, are also discussed. HighlightsBrain edema is a common feature in ALF and CLD. HE is inconsistently associated with the presence of brain edema. Fibrous and protoplasmic astrocytes are differentially implicated in the pathogenesis of HE. The pathogenesis of HE is multifactorial causing an array of neurological symptoms.

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Increase brain lactate in hepatic encephalopathy: Cause or consequence?

Cited by 20 publications

References 98 publications

Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake

Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake

Ammonia mediates cortical hemichannel dysfunction in rodent models of chronic liver disease

Brain edema in acute liver failure and chronic liver disease: Similarities and differences

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