The acidifying effect of lactate is neutralized by the alkalinizing effect of hypoalbuminemia in non-paracetamol-induced acute liver failure
Introduction
Elevated levels of lactate are common in acute liver failure (ALF) [1], [2]. Decreased hepatic lactate metabolism and increased hepatic lactate production have been demonstrated in ALF [3]. While frank lactic acidosis is common in paracetamol-induced ALF [4], patients with non-paracetamol-induced ALF often present with elevated lactate but without acidosis [5]. Moreover, concentrations of blood lactate did not correlate well, or not at all, with blood pH [5], [6]. Such failure of lactate to acidify the blood was termed ‘stress hyperlactatemia’ and was ascribed to sources of lactate production other than depressed bioenergetic cellular state [7].
Lactic acid is more than 99% dissociated into Lactate− and protons (H+) at physiological pH [8]. According to the physical–chemical acid–base theory, elevated strong anions such as lactate diminish the strong ion difference and thus cause metabolic acidosis [9]. One possible reason for an anion failing to acidify blood is the additional elevation of a base or the lack of another acid [9]. Such a constellation would be addressed as a concealed metabolic acidosis.
Multiple offsetting metabolic acid–base disorders could be revealed by means of the physical–chemical acid–base approach in chronic liver disease [10]. Albumin is a weak acid and decreases especially in non-paracetamol-induced ALF. A lack of albumin causes metabolic alkalosis [11]. We hypothesized that hypoalbuminemic alkalosis accounts for the absence of an apparent metabolic acidosis in presence of elevated lactate in ALF. The aim of this study was to determine whether the acidifying effect of lactate is neutralized by the alkalinizing effect of hypoalbuminemia in acute liver failure.
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Patients and methods
Patients with ALF admitted to a medical ICU of a university hospital during a four-year period were studied. A priori approval of the local Ethics Committee and informed consent from patients were obtained. ALF was defined and classified according to O’Grady [12]. Clinical and demographic parameters were obtained from the standard diagnostic procedures of ALF. The acute physiology and chronic health evaluation (APACHE) III score was used to assess severity of illness [13].
Demographic and clinical features
Forty-six patients (16 male, 30 female), median age 36 (21–53) with ALF were studied. Cause of ALF was Amanita intoxication (n = 14, 30%), acute hepatitis B (n = 10, 22%), drug-induced (n = 8, 17%), Wilsons’s disease (n = 3, 7%), acute hepatitis A (n = 1, 2%), acute hepatitis C (n = 1, 2%), autoimmune hepatitis (n = 1, 2%) and unknown (n = 8, 17%). Frequency of hyperacute, acute and subacute ALF was 14 (30%), 29 (63%) and 3 (7%), respectively. Maximum individual AST and ALT were 1105 (358–2495) and 1730
Discussion
In ALF various tissues, including the lungs, release lactate [6]. The liver itself becomes a net-producer of lactate in such a condition [3]. So far, no evidence supports a connection between elevated lactate and acid–base state in ALF. H+ concentration and standard bicarbonate as measures of the global and metabolic acid–base state, respectively, did not correlate with lactate [6]. Even a weak positive correlation between lactate and pH had been reported [5]. Contrary to paracetamol-induced
References (23)
- et al.
Lactic acidosis in fulminant hepatic failure. Some aspects of pathogenesis and prognosis
J Hepatol
(1985) - et al.
Acid–base disturbances in liver disease
J Hepatol
(1986) - et al.
Hyperlactatemia and pulmonary lactate production in patients with fulminant hepatic failure
Chest
(1999) - et al.
Hypoproteinemic alkalosis
Am J Med
(1986) - et al.
The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults
Chest
(1991) - et al.
A physical chemical approach to the analysis of acid–base balance in the clinical setting
J Crit Care
(1993) Alterations in carbohydrate metabolism during stress: a review of the literature
Am J Med
(1995)- et al.
Splanchnic metabolism of fuel substrates in acute liver failure
J Hepatol
(2000) Hyperlactatemia in acute liver failure: decreased clearance versus increased production
Crit Care Med
(2001)- et al.
Liver and intestinal lactate metabolism in patients with acute hepatic failure undergoing liver transplantation
Crit Care Med
(2001)