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ABG Interpretation
 
 

Lactate

March 4th, 2023
 
 
 
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Overview

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

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.

Overview

  • Note

  • D-lactate is an isomer of lactate produced by bacteria that will not be measured by conventional lactate testing.
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