Causes of lactic acidosis
- Michael Emmett, MD
Michael Emmett, MD
- Editor-in-Chief — Nephrology
- Section Editor — Fluid and Electrolytes
- Chief of Internal Medicine
- Baylor University Medical Center
- Harold Szerlip, MD, FACP, FCCP, FASN, FNKF
Harold Szerlip, MD, FACP, FCCP, FASN, FNKF
- Director, Nephrology Division, Baylor University Medical Center, Dallas
- Program Director, Nephrology Training Program, Baylor University Medical Center
- Clinical Professor of Medicine, Texas A&M College of Medicine
- Adjunct Professor of Medicine, Texas College of Osteopathic Medicine
INTRODUCTION AND DEFINITION
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, increased lactate levels can also be observed with a normal anion gap (most often if hypoalbuminemia is not identified and used to correct the anion gap). 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 lactate production exceeds lactate clearance. The increase in lactate production is usually caused by impaired tissue oxygenation, either from decreased oxygen delivery or a defect in oxygen utilization because of inhibition of the mitochondrial pyruvate dehydrogenase complex, both of which lead to increased anaerobic metabolism. (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 . 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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