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
Lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients. It is associated with an elevated anion gap and a plasma lactate concentration above 4 meq/L. Impaired tissue oxygenation, leading to increased anaerobic metabolism, is usually responsible for the rise in lactate production. (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 mainly reflected by the ratio of oxidized and reduced nicotine adenine dinucleotide (ie, NAD+ [oxidized form] and NADH [reduced form]).
NAD+ and NADH are involved in many cellular redox reactions, serving, respectively, as an electron acceptor or an electron donor. One of these cellular redox reactions is the equilibrium between pyruvic acid and lactic acid, a reaction catalyzed by the enzyme lactate dehydrogenase (figure 1). Thus, the ratio of pyruvate and lactate is influenced by the ratio of NAD+ and NADH, such that a reduced redox state (ie, low NAD+/NADH ratio) is associated with a shift in the ratio from pyruvate to lactate. Many of the factors that produce a reduced redox state also accelerate pyruvate generation and simultaneously impair mitochondrial oxidation, thereby increasing pyruvate and lactate generation (see 'Mitochondrial dysfunction' below). These factors include inadequate oxygen delivery or utilization, and rapid oxidation of certain substrates, such as ethanol.
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