Location of Repository

Circulating anions usually associated with the Krebs cycle in patients with metabolic acidosis

By L.G. Forni, W. McKinnon, Gwyn A. Lord, D.F. Treacher, J.M.R. Peron and P.J. Hilton

Abstract

Introduction:\ud \ud Acute metabolic acidosis of non-renal origin is usually a result of either lactic or ketoacidosis, both of which are associated with a high anion gap. There is increasing recognition, however, of a group of acidotic patients who have a large anion gap that is not explained by either keto- or lactic acidosis nor, in most cases, is inappropriate fluid resuscitation or ingestion of exogenous agents the cause.\ud \ud \ud Methods:\ud \ud Plasma ultrafiltrate from patients with diabetic ketoacidosis, lactic acidosis, acidosis of unknown cause, normal anion gap metabolic acidosis, or acidosis as a result of base loss were examined enzymatically for the presence of low molecular weight anions including citrate, isocitrate, α-ketoglutarate, succinate, malate and d-lactate. The results obtained from the study groups were compared with those obtained from control plasma from normal volunteers.\ud \ud \ud Results:\ud \ud In five patients with lactic acidosis, a significant increase in isocitrate (0.71 ± 0.35 mEq l-1), α-ketoglutarate (0.55 ± 0.35 mEq l-1), malate (0.59 ± 0.27 mEq l-1), and d-lactate (0.40 ± 0.51 mEq l-1) was observed. In 13 patients with diabetic ketoacidosis, significant increases in isocitrate (0.42 ± 0.35 mEq l-1), α-ketoglutarate (0.41 ± 0.16 mEq l-1), malate (0.23 ± 0.18 mEq l-1) and d-lactate (0.16 ± 0.07 mEq l-1) were seen. Neither citrate nor succinate levels were increased. Similar findings were also observed in a further five patients with high anion gap acidosis of unknown origin with increases in isocitrate (0.95 ± 0.88 mEq l-1), α-ketoglutarate (0.65 ± 0.20 mEq l-1), succinate (0.34 ± 0.13 mEq l-1), malate (0.49 ± 0.19 mEq l-1) and d-lactate (0.18 ± 0.14 mEq l-1) being observed but not in citrate concentration. In five patients with a normal anion gap acidosis, no increases were observed except a modest rise in d-lactate (0.17 ± 0.14 mEq l-1).\ud \ud \ud Conclusion:\ud \ud The levels of certain low molecular weight anions usually associated with intermediary metabolism were found to be significantly elevated in the plasma ultrafiltrate obtained from patients with metabolic acidosis. Our results suggest that these hitherto unmeasured anions may significantly contribute to the generation of the anion gap in patients with lactic acidosis and acidosis of unknown aetiology and may be underestimated in diabetic ketoacidosis. These anions are not significantly elevated in patients with normal anion gap acidosis

Topics: bcs
Publisher: Springer
Year: 2005
OAI identifier: oai:eprints.bbk.ac.uk.oai2:301

Suggested articles

Preview

Citations

  1. Afifi AH: Experimental and clinical studies on lactate and pyruvate as indicators of the severity of acute circulatory doi
  2. (1970). Afifi AH: Experimental and clinical studies on lactate and pyruvate as indicators of the severity of acute circulatory failure (shock). Circulation doi
  3. (2002). Argent A: Correction of the anion gap for albumin in order to detect occult tissue anions in shock. Arch Dis Child
  4. (2001). Base excess and lactate as prognostic indicators for patients admitted to intensive care. Intensive Care Med doi
  5. (2003). Closing the gap on unmeasured anions. Crit Care
  6. (1992). Falk JL: Lactic acidosis in critical illness. Crit Care Med doi
  7. (1986). Fencl V: Acid-base effects of altering plasma protein concentration in human blood in vitro.
  8. (1983). Hassinen IE: Tricarboxylic acid cycle metabolites during ischemia in isolated perfused rat heart.
  9. (2004). Initial pH, base deficit, lactate, anion gap, strong ion difference, and strong ion gap predict outcome from major vascular injury. Crit Care Med doi
  10. (1978). Metabolic responses to cardiac hypoxia. Increased production of succinate by rabbit papillary muscles. Circ Res doi
  11. (1991). MH: Unaccounted for anion in metabolic acidosis during severe sepsis in humans. Crit Care Med doi
  12. (1990). MH: Unmeasured anion during severe sepsis with metabolic acidosis. Circ Shock doi
  13. (1994). Natural history and course of acquired lactic acidosis in adults. The DCA-Lactic Acidosis Study Group . doi
  14. (1996). PJ: Use of continuous haemofiltration to assess the rate of lactate metabolism in acute renal failure. Clin Sci (Lond)
  15. (1999). Sahlin K: Actively phosphorylating mitochondria are more resistant to lactic acidosis than inactive mitochondria.
  16. (1974). Siesjo BK: Influence of complete ischemia on glycolytic metabolites citric acid cycle intermediates and associated amino acids in the rat cerebral cortex. Brain Res doi
  17. (1967). Spontaneous decarboylation of oxalacetic acid. doi
  18. (1998). T: Cardiac accumulation of citrate during brief myocardial ischaemia and reperfusion in the pig in vivo. Acta Physiol Scand doi
  19. (2005). The meaning of acid-base abnormalities in the intensive care unit: part III - effects of fluid administration. Crit Care
  20. (1984). Thijs LG: Distribution of cardiac output, oxygen consumption and lactate production in canine endotoxin shock. Cardiovasc Res doi
  21. (1998). Treacher DF: Bicarbonate-based haemofiltration in the management of acute renal failure with lactic acidosis. QJM doi
  22. (1983). Woods HF: Lactic acidosis revisited. Diabetes doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.