Metabolic Acidosis

CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3


‘In metabolic acidosis, there is either additional acid (H+) production on the right side of the equation, or direct loss of bicarbonate which drives the equation to the right, increasing H+ and lowering pH.’

The consequent reduction in pH stimulates the respiratory centre to increase ventilation and lower pCO2. This in turn drives the reaction to the left, lowering both bicarbonate and H+ to achieve compensation. There is also increased H+ secretion in the kidneys (linked to increased HCO3 reabsorption), further lowering H+.

Further classification of a metabolic acidosis depends on the anion gap – the difference between the major plasma cations (Na+ and K+) and anions (Cl and HCO3):

Anion gap = (Na+ + K+) – (Cl + HCO3)

A normal anion gap is in the range 9-14 mmol/l.

Calculating the anion gap often helps identify the cause of the acidosis.
Causes of a raised anion gap metabolic acidosis

A raised anion gap can be due to excess acid production or ingestion contributing extra H+:

  • Methanol poisoning – with formic acid formation
  • Uraemia from advanced renal failure
  • Diabetes also producing ketoacidosis
  • Paraldehyde poisoning – with acetic and chloracetic acid formation
  • Isoniazid / Iron overload
  • Lactate from tissue hypoxia (respiratory compromise, sepsis, ischaemic bowel
  • Ethylene glycol poisoning (with glycolic and lactic acid production) or Ethanol poisoning producing ketoacidosis
  • Rhabdomyolysis
  • Salicylate from aspirin overdose


For example, in a patient with diabetic ketoacidosis, without any compensation:

  • pH    7.22   
  • pCO2   4.8 kPa
  • pO2   12.1 kPa
  • Bicarbonate  15 mmol/L
  • Na+  138 mmol/L
  • K+  4.6 mmol/L
  • Cl-  104 mmol/L

The pH is low, the pCO2 is normal and the bicarbonate is low indicating a metabolic acidosis. The anion gap is raised at 23.6 due to the ketoacidosis.

Causes of a normal anion gap metabolic acidosis

In a normal anion gap acidosis, bicarbonate is lost from the gut or the kidneys and there is a raised chloride, which compensates for the extra cations, thus keeping the gap normal. This occurs as a result of reabsorption of sodium chloride via the kidneys:

  • H+ secretion failure from the kidneys – types 1 and 4 renal tubular acidosis
  • Acetazolamide
  • Renal tubular acidosis (type 2) with loss of HCO3 from the kidneys
  • Diarrhoea – loss of lower GI secretions including HCO3
  • Ureteropelvic fistula – loss of HCO3 containing secretions
  • Post-hypocapnia
  • Spironolactone

Irrespective of its cause, a metabolic acidosis has a detrimental effect on the cardiovascular system: there is impaired cardiac contractility and a reduced response to catecholamines. There is also increased pulmonary vascular resistance and decreased hepatic and renal perfusion. The threshold for ventricular fibrillation is lowered.

Remember: HARDUPS

Note: Page content citation [2-4]