fumarates and Hepatic-Encephalopathy

Posthepatectomy coma was produced in 13 dogs and the cerebrums were biopsied for analysis of concentrations of glucose, glucose-6-phosphate, dihydroxyacetone-phosphate, phosphoenolpyruvate, pyruvate, lactate, citrate, alpha-ketogulutarate, fumarate, malate, oxaloacetate, adenosinetriphosphate, ammonia, and glutamine as well as for activities of glucokinase, phosphofructokinase, pyruvate kinase, isocitrate dehydrogenase, glutamate dehydrogenase, malate dehydrogenase, and malic enzyme. There were no differences from normal in the brain glycolytic substrate concentrations. Four of the Krebs cycle substrates were significantly reduced, but not differently than in dogs sedated for 24 hours. The glycolytic pathway, Krebs cycle, and related enzyme activities were not significantly altered. Cerebral adenosine triphosphate concentration was unchanged but the concentrations of ammonia and glutamine increased threefold.

Topics: Adenosine Triphosphatases; Ammonia; Animals; Brain; Citrates; Citric Acid Cycle; Dihydroxyacetone Phosphate; Dogs; Fumarates; Glucose; Glucosephosphates; Glutamine; Glycolysis; Hepatectomy; Hepatic Encephalopathy; Ketoglutaric Acids; Lactates; Malates; Oxaloacetates; Oxidoreductases; Phosphoenolpyruvate; Phosphotransferases; Pyruvates

In 28 patients with fulminant hepatic failure alkalaemia was present in 49 of a total of 65 observations. Alkalaemia was due primarlily to a low Pa, C02 in 30 instances and to raised plasma bicarbonate in 16 instances. Blood lactate, pyruvate, and acetoacetate were significantly raised, and in individual cases, blood citrate, succinate, and fumarate were elevated. Blood citrate rose progressively as the clinical condition worsened. Metabolic acidosis was only present in four patients. In three of these patients, all of whom had taken an overdose of paracetamol, the acidosis was severe, present before the onset of clinical heparic failure, and associated with hypoglycaemiaand mild hypotension. In two of these patients the acidosis was shown to be due to accumulation of lactic acid. Plasma free fatty acid concentrations were elevated out of proportion to the degree of ketosis.

Topics: Acetoacetates; Acid-Base Equilibrium; Acidosis; Acute Disease; Alkalosis; Bicarbonates; Carbon Dioxide; Citrates; Fatty Acids, Nonesterified; Fumarates; Hepatic Encephalopathy; Humans; Ketoglutaric Acids; Ketone Bodies; Lactates; Liver Diseases; Oxygen; Partial Pressure; Pyruvates; Succinates; Triglycerides