Under conditions of adequate or near-adequate tissue oxygenation, glucose is metabolized for energy production using the aerobic metabolic pathway that converts glucose metabolic products to pyruvate that is, in turn, metabolized in the citric acid (Krebs) cycle. Under conditions of severe tissue hypoxia, aerobic metabolism cannot function properly, and glucose metabolic products at the pyruvate state stage are converted to lactate (lactic acid) by anaerobic metabolism. Therefore, increase in blood lactate is one indication of significantly decreased tissue oxygenation. Compared to other indicators of abnormal oxygen availability, PO2 decrease is best at suggesting decreased pulmonary alveolar uptake of oxygen, oxygen saturation methods demonstrate arterial oxygen content, and blood lactate shows the metabolic consequence of tissue hypoxia. In general, blood lactate is a fairly sensitive and reliable measurement of tissue hypoxia. It can be used to diagnose clinically important tissue hypoxia, to determine (roughly) the degree of hypoxia, to estimate tissue oxygen debt (the size of the accumulated oxygen deficit accumulated during a period of hypoxia), and to monitor the effect of therapy. Lactate can be increased in local ischemia if severe or extensive enough (e.g., grand mal seizures, or severe exercise; mesenteric artery insufficiency) as well as generalized ischemia (cardiac decompensation, shock, or carbon monoxide poisoning). The majority of patients exhibiting relatively large increases in blood lactate have metabolic acidosis, either primary or mixed (with respiratory acidosis or alkalosis).

Lactic acidosis has been divided into two groups: tissue hypoxia (discussed above) and conditions not involving significant tissue hypoxia. In the latter group are included severe liver disease (decreased metabolism of lactate), malignancy, drug-induced conditions (e.g., from cyanide, ethanol, and methanol), and certain inborn errors of metabolism. Idiopathic lactic acidosis associated with diabetes appears to combine a minor element of tissue hypoxia with some unknown triggering factor. In general, etiologies not primarily associated with tissue hypoxia tend to have lesser degrees of blood lactate elevation and better survival (with the exception of idiopathic lactic acidosis). However, there is a very significant degree of overlap in survival between the two classification groups. Another problem is controversy over definition of lactic acidosis. One frequently accepted definition is a lactate reference range of 0.5-1.5 mEq/L (mmol/L), hyperlactatemia when blood lactate persists in the 2.0-5.0 mEq/L range, and lactic acidosis when blood lactate exceeds 5 mEq/L (mmol/L) accompanied by metabolic acidosis. RBC metabolism increases lactate, so that specimens need special preservatives plus immediate ice cooling with early separation of the plasma, or else a bedside whole-blood analyzer.