Hepatic blood flow and metabolism in severe falciparum malaria: Clearance of intravenously administered galactose

Abstract

Hypoglycaemia and lactic acidosis are important manifestations of severe falciparum malaria. To investigate hepatic gluconeogenesis in acute falciparum malaria, liver blood flow and galactose clearance were estimated in seven adult patients with moderately severe infection and seven patients with severe infection (three of whom died later). Nine patients were restudied in convalescence. Liver blood flow, determined from the plasma clearance of Indocyanine Green, was lower in acute illness than in convalescence [16.1 (7.0) versus 23.9 (7.2) ml min-1kg-1, mean (SD)[, but this difference was not statistically significant (P < 0.15). There was a significant inverse correlation between admission venous plasma lactate concentrations and ihe liver blood flow estimated from the clearance of Indocyanine Green (r(s) = 0.71, P = 0.004). The plasma clearance of galactose after intravenous injection was similar in the acute [15.4 (4.90) ml min-1kg-1[ and convalescent study [12.8 (2.1) ml min-1kg-1]. The ratio of galactose clearance to Indocyanine Green clearance was significantly higher in acute disease [1.41 (0.51)] than in convalescence [0.70 (0.34)], largely because of the elevated ratios in severely ill patients [1.48 (0.50)]. The rise in blood glucose concentration after galactose administration was significantly higher during acute illness [1.48 (0.72) mmol/l] than in convalescence [0.67 (0.41) mmol/l, P = 0.022], but the insulin response was similar, indicating reduced tissue insulin sensitivity. There was no significant change in the plasma concentrations of other metabolites (lactate, pyruvate, alanine and triacylglycerol) in either study. These results suggest that the segment of the glycolytic pathway between galactose and glucose is unimpaired in patients with severe falciparum malaria. Since galactose does not stimulate insulin secretion directly and does not appear to increase plasma lactate concentrations, this simple sugar may be an alternative to glucose in the treatment of malaria-associated hypoglycaemia.