Test Findings
 

Hyperlactataemia

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Overview

  • 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
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