Clinical meaning
Lactic acidosis occurs when lactate production exceeds lactate clearance, resulting in serum lactate levels above 4 mmol/L (or >2 mmol/L with concurrent metabolic acidosis). Lactate is the end product of anaerobic glycolysis -- when cells cannot perform oxidative phosphorylation (aerobic metabolism) due to insufficient oxygen delivery or mitochondrial dysfunction, pyruvate is converted to lactate by lactate dehydrogenase (LDH) to regenerate NAD+ and allow glycolysis to continue.
Lactic acidosis is classified into two types. Type A (hypoxic) is caused by tissue hypoperfusion and hypoxia: septic shock (most common cause -- both distributive shock reducing oxygen delivery AND mitochondrial dysfunction from inflammatory mediators), cardiogenic shock (pump failure reducing cardiac output), hypovolemic shock (blood/fluid loss reducing circulating volume), severe anemia (reduced oxygen-carrying capacity), carbon monoxide poisoning (displaces oxygen from hemoglobin), and mesenteric ischemia. Type B (non-hypoxic) occurs without overt tissue hypoxia: metformin toxicity (inhibits mitochondrial complex I), liver failure (impaired lactate clearance -- the liver normally clears 60% of circulating lactate via the Cori cycle), thiamine deficiency (thiamine is a cofactor for pyruvate dehydrogenase, which converts pyruvate to acetyl-CoA for the Krebs cycle), malignancy (Warburg effect -- cancer cells preferentially use glycolysis even in the presence of oxygen), seizures (excessive muscle activity), and medications (nucleoside reverse transcriptase inhibitors causing mitochondrial toxicity).
In sepsis, lactate serves as both a diagnostic marker and a resuscitation endpoint. An initial lactate >4 mmol/L identifies patients at high risk for mortality. Serial lactate measurements guide the adequacy of resuscitation: lactate clearance of >10-20% per 2 hours indicates improving tissue perfusion and is associated with better outcomes. Failure of lactate to clear despite fluid resuscitation and vasopressors suggests ongoing tissue hypoperfusion or mitochondrial dysfunction and carries a mortality exceeding 50%.