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Causes of lactic acidosis

Michael Emmett, MD
Harold Szerlip, MD, FACP, FCCP, FASN, FNKF
Section Editor
Richard H Sterns, MD
Deputy Editor
John P Forman, MD, MSc


Lactate levels greater than 2 mmol/L represent hyperlactatemia, whereas lactic acidosis is generally defined as a serum lactate concentration above 4 mmol/L. Lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients. Although the acidosis is usually associated with an elevated anion gap, moderately increased lactate levels can be observed with a normal anion gap (especially if hypoalbuminemia exists and the anion gap is not appropriately corrected). When lactic acidosis exists as an isolated acid-base disturbance, the arterial pH is reduced. However, other coexisting disorders can raise the pH into the normal range or even generate an elevated pH. (See "Approach to the adult with metabolic acidosis", section on 'Assessment of the serum anion gap' and "Simple and mixed acid-base disorders".)

Lactic acidosis occurs when lactic acid production exceeds lactic acid clearance. The increase in lactate production is usually caused by impaired tissue oxygenation, either from decreased oxygen delivery or a defect in mitochondrial oxygen utilization. (See "Approach to the adult with metabolic acidosis".)

The pathophysiology and causes of lactic acidosis will be reviewed here. The possible role of bicarbonate therapy in such patients is discussed separately. (See "Bicarbonate therapy in lactic acidosis".)


A review of the biochemistry of lactate generation and metabolism is important in understanding the pathogenesis of lactic acidosis [1]. Both overproduction and reduced metabolism of lactate appear to be operative in most patients.

Cellular lactate generation is influenced by the "redox state" of the cell. The redox state in the cellular cytoplasm is reflected by the ratio of oxidized and reduced nicotine adenine dinucleotide (ie, NAD+ [oxidized form] and NADH [reduced form]).

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Literature review current through: Nov 2017. | This topic last updated: Sep 19, 2017.
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