lactic acid

Lactate is produced when pyruvate, generated from glycolysis, is converted by lactate dehydrogenase (LDH) using NADH, regenerating NAD+ to allow glycolysis to continue in the absence of adequate oxidative phosphorylation. This occurs physiologically during strenuous exercise (anaerobic glycolysis in skeletal muscle) and pathologically in states of tissue hypoperfusion or mitochondrial dysfunction.

Lactic acidosis is classified into two types: - Type A: Due to tissue hypoxia/hypoperfusion — seen in sepsis, cardiogenic/hypovolemic shock, severe anemia, carbon monoxide poisoning, and seizures. - Type B: Occurs without overt hypoxia — caused by drugs/toxins (metformin, propylene glycol, isoniazid, antiretrovirals, cyanide), liver failure (impaired lactate clearance), malignancy (Warburg effect, especially lymphomas/leukemias), thiamine deficiency (impairs pyruvate dehydrogenase), and inborn errors of metabolism (e.g., pyruvate dehydrogenase deficiency).

Clinically, elevated lactate is used as a prognostic marker in sepsis (part of the Surviving Sepsis Campaign bundles) and to assess perfusion status in critically ill patients. Lactate >4 mmol/L in sepsis is associated with increased mortality and is used to guide resuscitation (fluid administration, vasopressors). Lactic acidosis presents with an elevated anion gap metabolic acidosis, and can cause symptoms of nausea, vomiting, abdominal pain, tachypnea (Kussmaul breathing), and altered mental status.

Diagnosis involves measuring serum lactate levels (venous or arterial) along with arterial blood gas to assess acid-base status and anion gap. Treatment focuses on addressing the underlying cause: fluid resuscitation and source control in sepsis, discontinuing offending drugs, treating malignancy, or thiamine repletion.

Key exam associations: Metformin-associated lactic acidosis (MALA) — caution in renal impairment; Warburg effect in cancer cells (aerobic glycolysis with lactate production even with adequate oxygen, useful in PET imaging with FDG); D-lactic acidosis in short bowel syndrome due to bacterial fermentation of carbohydrates.