D-Lactic Acidosis: A Review of Clinical Presentation, Biochemical Features, and Pathophysiologic Mechanisms (original) (raw)
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Lactate is one of the most crucial intermediates in carbohydrate and nonessential amino acid metabolism. The complexity of cellular interactions and metabolism means that lactate can be considered a waste product for one cell but a useful substrate for another. The presence of elevated lactate levels in critically ill patients has important implications for morbidity and mortality. In this review, we provide a brief outline of the metabolism of lactate, the pathophysiology of lactic acidosis, the clinical significance of D-lactate, the role of lactate measurement in acutely ill patients, the methods used to measure lactate in blood or plasma and some of the methodological issues related to interferences in these assays, especially in the case of ethylene glycol poisoning.
D-lactate in human and ruminant metabolism
The Journal of nutrition, 2005
D-Lactate is normally present in the blood of mammals at nanomolar concentrations due to methylglyoxal metabolism; millimolar D-lactate concentrations can arise due to excess gastrointestinal microbial production. Grain overload in ruminants, short-bowel syndrome in humans, and diarrhea in calves can all result in profound D-lactic acidemia, with remarkably similar neurological manifestations. In the past, D-lactate was thought to be excreted mainly in the urine, and metabolized slowly by the enzyme D-␣-hydroxy acid dehydrogenase. More recent studies reported that mammals have a relatively high capacity for D-lactate metabolism and identified a putative mammalian D-lactate dehydrogenase. A growing body of literature is also emerging describing subclinical elevation of D-lactate as an indicator of sepsis and trauma. This article describes advances in the understanding of D-lactate metabolism, D-lactic acidosis in ruminants and humans, and subclinical elevation of D-lactate.
D-lactic acidosis: Turning sugar into acids in the gastrointestinal tract
Kidney International, 1996
PERSPECTIVES IN CLINICAL NEPHROLOGY D-lactic acidosis: Turning sugar into acids in the gastrointestinal tract While an appreciable quantity of organic acids is produced each day by bacterial metabolism in the gastrointestinal (GI) tract [1, 2], there is usually no acid-base consequence from this acid load because the rate of production of these acids does not exceed the capacity of the normal host to metabolize them. Nevertheless, after jejuninoileal bypass surgery or substantial small bowel resection, appreciable quantities of acids such as D-lactic acid may accumulate [3-12]. Hence the stage is set for the development of D-lactic acidosis when there is a combination of altered GI anatomy and a change in bacterial flora (such as the use of antibiotics). A less well recognized clinical association is the aggravation of the clinical picture when more glucose is supplied to these bacteria [13-16]. The extent to which production of organic acids will cause metabolic acidosis also depends on biochemical considerations. Not only must one consider whether the patient has the enzymatic machinery to metabolize each added acid, but one must also appreciate the limitations set by the overall rate of ATP turnover in cells [17] and the competition between fuels to be the substrate oxidized to regenerate the ATP needed to perform biologic work in individual cells [18]. Moreover, there is a quantitative relationship between H removal and ATP regeneration that differs between individual organic acids [19]. This manuscript is divided into two sections: first we shall discuss the normal metabolism and functions of organic acids produced in the GI tract; second, we shall consider the different types of presentation of organic acidosis where GI bacteria might have played a central role, highlighting biochemical aspects so that a more rational design for therapy can be suggested. Organic acids and the GI tract: Normal physiology There are two sources of organic acids in the GI tract, diet and endogenous production. Organic acids of dietary origin do not usually pose an acid-base threat because the quantity ingested is not large enough to exceed the capacity of the host to remove them by metabolic means. In addition, the intake of acids occurs together with their potassium (K) salts. For example, the citric acid load ingested each day is small and readily metabolized to neutral end-products so it only yields a net H load transiently. Metabolism of the K salt of citrate yields bicarbonate [20]. Overall, after metabolism of the organic acid and its K salt, bicarbonate ions are produced which minimize a threat from another H load. Accordingly, we shall focus on endogenous production of organic acids which are synthesized from neutral
D-Lactic Acidosis: An Underrecognized Complication of Short Bowel Syndrome
Gastroenterology Research and Practice, 2015
D-lactic acidosis or D-lactate encephalopathy is a rare condition that occurs primarily in individuals who have a history of short bowel syndrome. The unabsorbed carbohydrates act as a substrate for colonic bacteria to form D-lactic acid among other organic acids. The acidic pH generated as a result of D-lactate production further propagates production of D-lactic acid, hence giving rise to a vicious cycle. D-lactic acid accumulation in the blood can cause neurologic symptoms such as delirium, ataxia, and slurred speech. Diagnosis is made by a combination of clinical and laboratory data including special assays for D-lactate. Treatment includes correcting the acidosis and decreasing substrate for D-lactate such as carbohydrates in meals. In addition, antibiotics can be used to clear colonic flora. Although newer techniques for diagnosis and treatment are being developed, clinical diagnosis still holds paramount importance, as there can be many confounders in the diagnosis as will be...
A quantitative study on the metabolism of d(−) lactic acid in the rat and the rabbit
Comparative Biochemistry and Physiology Part B: Comparative Biochemistry, 1981
In rats and rabbits injected with (U-~4C)D-lactate labelled oL-lactate the exhalation of ~4CO2 as well as the renal excretion of D-lactate and of labelled metabolites were measured. 2. Dietary adaptation to DL-lactate had little effect on D-lactate metabolism in rats. Only with osmotic diuresis the initial rate of o-lactate excretion was significantly increased after adaptation. 3. The mean elimination of D-lactate by exhaled CO2, renal D-lactate, renal metabolites, and retention was Omol C/mmol C given) 855, 29, 37 and 83 in rats vs 440, 29, 29 and 508 in rabbits. 4. Differences between species in D-lactate metabolism were also indicated by the relationship between dose and oxidation rate as well as between dose and renal excretion which suggested different kidney threshold values for D-lactate.
Original Study Lactic Acid: Analysis Methods and Physiological Implications
Lactate is an end product of anaerobic metabolism of glucose. The blood concentration of lactate depends on the rate of production in muscle cells and red blood cells and the rate of metabolism in the liver. Lactic acidosis is a special case of metabolic acidosis due to increased production or underutilization of lactate, which is translated into hyperlactatemia when the level of the metabolite exceeds 5 mmol / L. This study recorded changes in blood lactate concentration of 50 patients with intellectual developmental disabilities (most institutionalized) from the acid-base imbalance frequently reported in association with these diagnoses. For the determination of lactate used an enzymatic method on the plate on Vitros clinical chemistry system 950. The anion deficit was calculated taking into account the concentrations of sodium ions, and bicarbonate cholure. Results showed metabolic acidosis 33, including 12 starters. Between the values calculated for the anion gap and blood lacta...
Kidney International, 2020
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A Report of Two Cases: Unlearning Lactic Acidosis
Clinical Practice and Cases in Emergency Medicine, 2021
Introduction The term “lactic acidosis” reinforces the misconception that lactate contributes to acidemia. Although it is common to discover an anion gap acidosis with a concomitant elevated lactate concentration, the two are not mutually dependent. Case Report Here we describe two patients exhibiting high lactate concentrations in the setting of metabolic alkalemia. Conclusion Lactate is not necessarily the direct cause of acid-base disturbances, and there is no fixed relationship between lactate and the anion gap or between lactate and pH. The term “metabolic acidosis with hyperlactatemia” is more specific than “lactic acidosis” and thus more appropriate.
Recurrent 'Lactic' Acidosis-a Cautionary Tale
Acute medicine, 2007
Lactic acidosis can be caused by a variety of pathological conditions. We present a case of recurrent 'lactic' acidosis, which was eventually diagnosed to be secondary to ethylene glycol poisoning. Though there are a handful of cases reported in the literature, it is not widely known that glycolic acid (a metabolite of ethylene glycol) is measured spuriously as lactic acid by some point of care analysers. Literature review would indicate that this is a rare but potentially confounding factor in diagnosis. Given the nature of the pathology, we would suggest that greater awareness of the problem is important. A 63-year old man presented to the Emergency Department with a 12 hour history of lightheadedness, unsteadiness, progressively worsening double vision, breathlessness and retrosternal pain. He denied substance misuse or alcohol ingestion. He had experienced a myocardial infarction 17 years