Altered Cerebral Blood Flow and Glucose Metabolism in Patients with Liver Disease and Minimal Encephalopathy

Lockwood, Alan H.; Yap, Eddy W. H.; Rhoades, Howard M.; Wong, Wai-Hoi

doi:10.1038/jcbfm.1991.66

Cited by 142 publications

(56 citation statements)

References 23 publications

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“…Regional variations similar to the current findings were found in 2 other 15 O-water PET studies of healthy controls and patients with minimal HE. 23,45 The reasons for the variations are not known but may be related to variations in the distribution of carbohydrate 45 and ammonia metabolism. 20,23 The reduction of the BBB permeability PS BBB for 13 Nammonia in HE patients to approximately two thirds of control values in cerebral cortex, basal ganglia, and cerebellum is a novel finding of the current study.…”

Section: Discussionmentioning

confidence: 99%

Brain metabolism of 13N‐ammonia during acute hepatic encephalopathy in cirrhosis measured by positron emission tomography†

et al. 2006

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, PS BBB , was 0.21 mL blood/min/mL tissue in patients with HE, 0.31 in patients without HE, and 0.34 in healthy controls; similar differences were seen in basal ganglia and cerebellum. Metabolic trapping of blood 13 N-ammonia in the brain showed neither regional, nor patient group differences. Mean net metabolic flux of ammonia from blood into intracellular glutamine in the cortex was 13.4 mol/min/L tissue in patients with cirrhosis with HE, 7.4 in patients without HE, and 2.6 in healthy controls, significantly correlated to blood ammonia. In conclusion, increased cerebral trapping of ammonia in patients with cirrhosis with acute HE was primarily attributable to increased blood ammonia and to a minor extent to changed ammonia kinetics in the brain. (HEPATOLOGY 2006;43:42-50.) T he role of ammonia in the pathogenesis of hepatic encephalopathy (HE) and possible deleterious effects on brain energy metabolism and neurotransmission has been extensively studied. [1][2][3][4] The effects of experimental porta-caval anastomosis with or without pharmacological manipulations of ammonia metabolism have been examined in rat brain, 5-13 and the effects of excess ammonia have been tested in astrocyte cell cultures. 14 Human studies of cerebral uptake and metabolism of ammonia included postmortem examinations of brain tissue from patients dying of HE 15 and biochemical analysis of jugular vein blood samples. [16][17][18] More recently, ammonia metabolism has been tested in positron emission tomography (PET) studies of monkeys, 19 healthy humans, [19][20][21][22] and patients with cirrhosis and minimal HE. [20][21][22][23] The 13 N-ammonia PET technique can, in conjunction with proper compartmental analysis, give quantitative estimates of kinetic parameters in awake subjects.Results of early PET studies by Phelps et al. 19 indicated the presence of regional variations in cerebral 13 N-ammonia uptake in normal human subjects. Lockwood et al. 20 subsequently emphasized that the metabolism of ammonia to glutamine in brain influences cerebral ammonia uptake and later calculated a global rate of cerebral 13 Nammonia metabolism in patients with cirrhosis with minimal HE and healthy controls. 21,22 Recently, Ahl et al., 23 using dynamic PET studies, found no significant difference of the permeability-surface area product of the trans-

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Section: Discussionmentioning

confidence: 99%

Brain metabolism of 13N‐ammonia during acute hepatic encephalopathy in cirrhosis measured by positron emission tomography†

et al. 2006

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“…Previous studies 20,21 indicate, however, that the Lp and membrane area are normal or even increased in patients with liver failure.…”

Section: Filtration Coefficient and Capillary Surfacementioning

confidence: 91%

Brain edema in liver failure: Basic physiologic principles and management

Larsen

Wendon

2002

Liver Transpl

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In patients with severe liver failure, brain edema is a frequent and serious complication that may result in high intracranial pressure and brain damage. This short article focuses on basic physiologic principles that determine water flux across the blood-brain barrier. Using the Starling equation, it is evident that both the osmotic and hydrostatic pressure gradients are imbalanced across the blood-brain barrier in patients with acute liver failure. This combination will tend to favor cerebral capillary water influx to the brain. In contrast, the disequilibration of the Starling forces seems to be less pronounced in patients with cirrhosis because the regulation of cerebral blood flow is preserved and the arterial ammonia concentration is lower compared with that of patients with acute liver failure. Treatments that are known to reverse high intracranial pressure tend to decrease the osmotic pressure gradients across the blood-brain barrier. Recent studies indicate that interventions that restrict cerebral blood flow, such as hyperventilation, hypothermia, and indomethacin, are also efficient in preventing edema and high intracranial pressure, probably by decreasing the transcapillary hydrostatic pressure gradient. In our opinion, it is important to recall that rational fluid therapy, adequate ventilation, and temperature control are of direct importance to controlling cerebral capillary water flux in patients with acute liver failure. These simple interventions should be secured before more advanced experimental technologies are instituted to treat these patients.

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“…Ammoniainduced alterations in cerebral blood flow and glucose metabolism have also been described. 21 Treatment with lactulose is of benefit in patients with MHE. 2,22,23 The possible efficacy of an alternative approach to modulating the gut microecology and acidifying the gut lumen for therapeutic gain in cirrhotic patients with MHE, namely treatment with synbiotics (probiotics and fermentable fiber), has not previously been studied.…”

Section: Inimal Hepatic Encephalopathy (Mhe) In Pa-mentioning

confidence: 99%

Synbiotic modulation of gut flora: Effect on minimal hepatic encephalopathy in patients with cirrhosis

Liu¹,

Duan²,

Ha³

et al. 2004

Hepatology

569

429

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Minimal hepatic encephalopathy (MHE) is an important disorder that may seriously impair daily functioning and quality of life in patients with cirrhosis. Treatment with lactulose is of benefit. The possible role of synbiotics (probiotics and fermentable fiber) has not been assessed. We screened 97 consecutive cirrhotic patients without overt hepatic encephalopathy for MHE using the number connection test and measurement of brainstem auditory evoked potentials. MHE, defined by abnormality on at least one test modality, was present in 58 (60%) patients. Fifty-five of these patients with MHE were randomized to receive a synbiotic preparation (n ‫؍‬ 20), fermentable fiber alone (n ‫؍‬ 20), or placebo (n ‫؍‬ 15) for 30 days. Cirrhotic patients with MHE were found to have substantial derangements in the gut microecology, with significant fecal overgrowth of potentially pathogenic Escherichia coli and Staphylococcal species. Synbiotic treatment significantly increased the fecal content of non-urease-producing Lactobacillus species at the expense of these other bacterial species. Such modulation of the gut flora was associated with a significant reduction in blood ammonia levels and reversal of MHE in 50% of patients. Synbiotic treatment was also associated with a significant reduction in endotoxemia. The Child-Turcotte-Pugh functional class improved in nearly 50% of cases. Treatment with fermentable fiber alone was also of benefit in a substantial proportion of patients. In conclusion, treatment with synbiotics or fermentable fiber is an alternative to lactulose for the management of MHE in patients with cirrhosis.

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Altered Cerebral Blood Flow and Glucose Metabolism in Patients with Liver Disease and Minimal Encephalopathy

Cited by 142 publications

References 23 publications

Brain metabolism of 13N‐ammonia during acute hepatic encephalopathy in cirrhosis measured by positron emission tomography†

Brain metabolism of 13N‐ammonia during acute hepatic encephalopathy in cirrhosis measured by positron emission tomography†

Brain edema in liver failure: Basic physiologic principles and management

Synbiotic modulation of gut flora: Effect on minimal hepatic encephalopathy in patients with cirrhosis

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