Elsevier

Journal of Hepatology

Volume 45, Issue 3, September 2006, Pages 387-392
Journal of Hepatology

The acidifying effect of lactate is neutralized by the alkalinizing effect of hypoalbuminemia in non-paracetamol-induced acute liver failure

https://doi.org/10.1016/j.jhep.2006.03.011Get rights and content

Background/Aims

Hyperlactatemia with unexplained absence of metabolic acidosis is observed in acute liver failure. In chronic liver disease offsetting metabolic acid–base disorders could be revealed by means of physical–chemical acid–base analysis. The purpose of this study was to determine whether the acidifying effect of lactate is neutralized by the alkalinizing effect of hypoalbuminemia in acute liver failure.

Methods

Serial arterial blood samples of 46 consecutive patients with non-paracetamol-induced acute liver failure were studied after admission to a medical ICU in a prospective investigation and compared to healthy controls. Acid–base state was assessed by quantitative physical–chemical analysis.

Results

Lactate was increased and albumin was decreased in patients with acute liver failure compared to healthy controls resulting in normal net metabolic acid–base state. The alkalinizing effect of hypoalbuminemia was neutralized by the acidifying effect of elevated lactate. This observation was confirmed in serial analysis during 5 days after admission.

Conclusions

The acidifying effect of lactate is neutralized by the alkalinizing effect of hypoalbuminemia in non-paracetamol-induced acute liver failure. The absence of apparent metabolic acidosis in the presence of elevated lactate can be explained by means of the physical–chemical acid–base model.

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.

Section snippets

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

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