Untitled

Abstract

Introduction 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.

A rapid LC–MS method for determination of plasma anion profiles of acidotic patients

“…In our study we found that the level of hydroxybutyrate increased significantly by almost twenty times in those with diabetes, but that the level of citrate did not differ significantly when compared to control values. It is widely reported elsewhere that plasma citrate is generally not elevated in acidosis [8,9], and we confirmed this in a previous study [1] as well as the results reported above.…”

“…Despite this, in clinical settings only lactate is routinely measured. We have previously shown that, in certain acidotic states, the level of circulating anions normally associated with intermediary metabolism are elevated and make a significant contribution towards the anion load that has previously been overlooked [1]. Although enzymatic methods exist to measure the absolute quantities of anions in the plasma, these methods are slow, cumbersome and provide a degree of accuracy that is very often unnecessary in clinical settings where a measurement of the absolute amount of an anion is often of secondary importance to its relative amounts and/or presence.…”

“…The levels of isocitrate and ␣-ketoglutarate were measured using our own enzyme assay utilising isocitrate dehydrogenase and ␣-ketoglutarate dehydrogenase respectively and their associated co-factors (Sigma Chemicals Ltd., Poole, UK). These assays are described elsewhere [1].…”

“…We have previously shown that the levels of anions normally associated with intermediary metabolism are altered in certain acidotic conditions and can contribute significantly to the development of the observed anion gap in these patients [1]. The absolute concentrations of these anions can be measured in a quantitative manner using enzyme assay.…”

Pathologic metabolism

“…33 Succinate accumulation might mediate platelet over-activation and thus potentiate untoward hypercoagulation in trauma patients. 34 Concomitant accumulation of lactate and TCA intermediates is suggestive that early metabolic alterations following trauma promote channeling to the TCA cycle of additional carbon substrates other than sugars, such as lipids and proteins.…”