MedSchool: Ace Your OSCEsThe Medical Company
GET - On the App Store
ABG Interpretation




  • Serum lactate is an important marker of prognosis and resolution in many critical illnesses.
      • Normal Range

      • 0.5 - 2.2 mmol/L

Lactate Physiology

    • Production

    • Lactate is produced via pyruvate metabolism under anaerobic or aerobic glycolytic conditions. In the presence of adequate oxygen and mitochondrial capacity, pyruvate is normally converted to acetyl CoA which then enters the Krebs cycle. In the absence of oxygen or in the presence of excessive glycolysis, pyruvate is shunted into lactate, produced by the enzyme lactate dehydrogenase.
    • Metabolism

    • Lactate is mainly metabolised by the liver and partially by myocytes, though the kidney plays more of a role in metabolism in the presence of hyperlactataemia.
    • Lactate Physiology


  • Hyperlactataemia reflects an imbalance between production and clearance of lactate. Accumulation of lactate is associated with acidosis; lactic acidosis is a high anion gap metabolic acidosis.
    • Aetiology

    • Hyperlactataemia has long been associated with anaerobic metabolism, which may be in the setting of heavy muscle activity, global hypoperfusion (e.g. shock), regional (e.g. mesenteric) ischaemia or severe oxygen depletion.
  • Aerobic glycolysis can also cause lactate accumulation, where in certain circumstances pyruvate is shunted to lactate despite adequate oxygenation. This is particularly stimulated by β2 activation due to stress, shock, adrenaline or beta 2 agonists (e.g. salbutamol). Aerobic glycolysis can also be seen in certain tumours.
  • Metformin causes reduced gluconeogenesis, which in the presence of renal failure can lead to lactate accumulation. Certain inherited or acquired conditions can cause hyperlactataemia though impaired pyruvate dehydrogenase inhibition; this is most relevant in sepsis and thiamine deficiency.
  • Hepatic dysfunction may cause lactate accumulation due to impaired clearance, though this does not typically occut until hepatic blood flow drops below 25%.
    • Causes of Hyperlactataemia

    • Type A - Reduced Tissue Oxygen Delivery

    • Anaerobic muscular activity - heavy exertion, seizures, severe asthma
    • Global hypoperfusion - shock, cardiac arrest, heart failure
    • Regional ischaemia - mesenteric, limb, burns, trauma, compartment syndrome, soft tissue necrosis
    • Reduced tissue oxygen delivery - severe hypoxia, severe anaemia, carbon monoxide poisoning
    • Type B1 - Underlying Disease

    • Poor clearance - fulminant liver failure, paracetamol overdose
    • Endogenous β2 stimulation - stress, shock, phaeochromocytoma
    • Pyruvate dehydrogenase impairment - sepsis, thiamine deficiency
    • Cancers - leukaemia, lymphoma, small cell lung cancer
    • Type B2 - Drugs & Toxins

    • Biguanides - metformin
    • Exogenous β2 stimulation - adrenaline, beta 2 agonists
    • Mitochondrial dysfunction - NRTIs, linezolid, cyanide
    • Type B3 - Inborn Errors of Metabolism

    • Enzyme deficiencies - e.g. pyruvate dehydrogenase deficiency

Lactate Gap

  • The lactate assay (LDH method) used by most labs is the gold standard, while the lactic acid oxidase method used by iSTAT machines produces false positives in the presence of glycolate (a metabolite of ethylene glycol).
  • If there is lactic acidosis and concern for ethylene glycol poisoning, the serum lactate should be measured using both assays; if there is a difference between the two (lactate gap) then ethylene glycol poisoning is likely present.


    • Note

    • D-lactate is an isomer of lactate produced by bacteria that will not be measured by conventional lactate testing.
Want more info like this?
  • Your electronic clinical medicine handbook
  • Guides to help pass your exams
  • Tools every medical student needs
  • Quick diagrams to have the answers, fast
  • Quizzes to test your knowledge
Sign Up Now


 Andersen L, Mackenhauer J, Roberts J, Berg K, Cocchi M, Donnino M. Etiology and Therapeutic Approach to Elevated Lactate Levels. Mayo Clin Proc. 2013;88:1127-1140.
Beasley R, McNaughton A, Robinson G. New look at the oxyhaemoglobin dissociation curve. The Lancet. 2006;367:1124-1126.
 Bellomo R. Bench-to-bedside review: lactate and the kidney. Critical Care 2002;6(4):1. Berend K, de Vries A, Gans R. Physiological Approach to Assessment of Acid-Base Disturbances. N Engl J Med. 2014;371:1434-1445. Brenner BE. Alveolar-arterial oxygen gradients. Ann Emerg Med. 1980;9:648-648. Brindley PG, Butler MS, Cembrowski G, Brindley DN. Falsely elevated point-of-care lactate measurement after ingestion of ethylene glycol. Canadian Medical Association Journal 2007;176(8):1097-9. Donnino MW, Carney E, Cocchi MN, Barbash I, et al. Thiamine deficiency in critically ill patients with sepsis. Journal of critical care 2010;25(4):576-81. Gore DC, Jahoor F, Hibbert JM, DeMaria EJ. Lactic acidosis during sepsis is related to increased pyruvate production, not deficits in tissue oxygen availability. Annals of surgery 1996;224(1):97. Kraut JA, Madias NE. Lactic acidosis. N Engl J Med. 2014; 371: 2309-2319. Levraut J, Ciebiera JP, Chave S, Rabary O, et al. Mild hyperlactatemia in stable septic patients is due to impaired lactate clearance rather than overproduction. Am J RespirCrit Care Med. 1998; 157(4 Pt 1):1021-6. Levy B, Gibot S, Franck P, Cravoisy A, et al. Relation between muscle Na+ K+ ATPase activity and raised lactate concentrations in septic shock: a prospective study. The Lancet 2005;365(9462):871-5. Marino PL. Marino's the ICU Book. Fourthition. ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2014. McCarter FD, Nierman SR, James JH, Wang L, et al. Role of skeletal muscle Na+–K+ ATPase activity in increased lactate production in sub–acute sepsis. Life sciences 2002;70(16):1875-88. Moreau R, Hadengue A, Soupison T, Kirstetter P, et al. Septic shock in patients with cirrhosis: hemodynamic and metabolic characteristics and intensive care unit outcome. Critical care medicine 1992;20(6):746. Perriello G, Jorde R, Nurjhan N, Stumvoll M, et al. Estimation of glucose-alanine-lactate-glutamine cycles in postabsorptive humans: role of skeletal muscle. American Journal of Physiology-Endocrinology and Metabolism 1995;269(3):E443-50. Phypers B, Pierce JT. Lactate physiology in health and disease. Continuing education in Anaesthesia, critical care & pain. 2006 Jun 1;6(3):128-32. Stacpoole PW. Lactic acidosis. Endocrinol Metab Clin North Am 1993 Jun; 22(2) 221-45.
Tunney P, Chinnan NK. Serum Lactate in Intensive Care: Practical Points and Pitfalls. inflammation. 2016;6:7.
 Vary TC. Sepsis-induced alterations in pyruvate dehydrogenase complex activity in rat skeletal muscle: effects on plasma lactate. Shock 1996;6(2):89-94. Venkatesh B, Morgan T, Garrett P. Measuring the lactate gap. The Lancet 2001;358(9295):1806.