Lactic acidosis is characterized by accumulation of excess lactic acid in the blood. Normally, the principal sources of this acid are the erythrocytes (which lack enzymes for aerobic oxidation), skeletal muscle, skin, and brain. Conversion of lactic acid to glucose and its oxidation principally by the liver but also by the kidneys represent the chief pathways for its removal. Hyperlactatemia and acidosis occur when lactate production exceeds lactate consumption. Causes include tissue hypoxia (global or local), disorders that increase epinephrine levels (severe asthma with excess beta-adrenergic agonist use, cardiogenic or hemorrhagic shock, pheochromocytoma), and drugs that impair oxidative phosphorylation (antiretroviral agents and propofol). Most cases of metformin-associated lactic acidosis occur in patients in whom there were contraindications to the use of metformin, in particular kidney failure. Metformin levels are usually greater than 5 mcg/L when metformin is implicated as the cause of lactic acidosis. Other causes of lactic acidosis include several inborn errors of metabolism and the MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes). D-lactic acidosis can occur in patients with short bowel syndrome when unabsorbed carbohydrates are presented as substrate for fermentation by colonic bacteria.