see also:

• sepsis / septicaemia
• https://emcrit.org/isepsis/isepsis-lactate-myths/

• the normal serum lactate range is up to 2 mmol/L (18 mg/dL)
• raised serum lactate > 4 mmol is often used as a marker for severe sepsis or localised ischaemia such as bowel or limb ischaemia and its use in at risk patients helps to detect occult severe sepsis or bowel ischaemia earlier
• high levels of serum lactate is associated with “lactic acidosis” which is one of the types of metabolic acidosis

• lactate is metabolized in the liver either by gluconeogenesis or oxidation with both reactions consuming a hydrogen ion
• lactic acid / lactate is produced when the amount of pyruvate exceeds the capacity of the Krebs cycle and is converted to lactate anaerobically at a rate higher than it can be metabolised - this may occur due to a range of mechanisms:
  • increased pyruvate production through the beta-2 adrenergic stress response which increases glycogenolysis and glucose production
  • reduced capacity of Krebs cycle:
    • relative thiamine deficiency
    • decreased activity of pyruvate dehydrogenase (this may be due to cytokine activity during a stress response)
    • cellular hypoxia
  • reduced hepatic metabolism of lactate

• type A lactic acidosis - “tissue hypoxia”
  • local ischaemia
    • ischaemic colitis
    • limb ischaemia
  • pre-terminal states causing global ischaemia
    • extremely severe global cellular impaired oxygenation where the cellular oxygen delivery falls below the global anaerobic threshold of adults which is about 4mls/kg/min and equates to a cardiac index of just over 1 L/minM² and Hb of around 4g/dl and this level generally only is reached in pre-terminal states
      • severe hypoxia
      • severe anaemia
      • cyanide poisoning
  • beta2 adrenergic driven stress responses
    • sepsis / septicaemia
    • seizures
    • severe exercise
    • severe asthma
    • etc.
• Type B1 lactic acidosis - disease states
  • diabetes mellitus (as well as causing acidosis via ketoacidosis)
  • liver disease
  • malignancy
  • sepsis
  • phaeochromocytoma
  • thiamine deficiency
• Type B2 lactic acidosis - drugs/ toxins
  • biguanides such as Metformin
  • ethanol/methanol/ethylene glycol/fructose/sorbitol
  • salicylate/paracetamol/salbutamol/nitroprusside/isoniazid/adrenaline
• Type B3 lactic acidosis - inborn errors of metabolism
  • Glucose-6-Pase deficiency
  • hypoglycaemia