Define metabolic acidosis. Discuss its classification using the anion gap, causes, clinical features, and management.

Definition

Metabolic acidosis is a primary disturbance characterised by a fall in serum bicarbonate (< 22 mEq/L) with a fall in arterial pH (< 7.35), caused by gain of acid, loss of bicarbonate, or failure of renal acid excretion. Respiratory compensation by hyperventilation lowers the PaCO2.

Respiratory Compensation — Winter's Formula

Expected PaCO2 = (1.5 × HCO3⁻) + 8 ± 2

• If the measured PaCO2 matches the predicted value, compensation is appropriate.
• If higher than predicted, there is a coexisting respiratory acidosis.
• If lower than predicted, there is a coexisting respiratory alkalosis (as in salicylate poisoning or sepsis).

Compensation is never complete — the pH does not return to normal — and a normal pH with abnormal bicarbonate and PaCO2 indicates a mixed disorder.

The Anion Gap

Anion gap = Na⁺ − (Cl⁻ + HCO3⁻), normally 8–12 mEq/L. It represents unmeasured anions, chiefly albumin, phosphate and sulphate.

Correction for albumin is essential — for every 1 g/dL fall in serum albumin below 4 g/dL, add 2.5 mEq/L to the measured gap. A hypoalbuminaemic patient may have a significant acid load with an apparently "normal" anion gap; this is a frequent clinical trap in cirrhosis and nephrotic syndrome.

Classification and Causes

High anion gap metabolic acidosis (HAGMA) — addition of an unmeasured acid:

Normal anion gap (hyperchloraemic) metabolic acidosis (NAGMA) — bicarbonate loss with chloride retention:

• Gastrointestinal loss: diarrhoea (the commonest cause worldwide), ileostomy, pancreatic or biliary fistula, ureteric diversion.
• Renal loss: renal tubular acidosis types 1, 2 and 4; carbonic anhydrase inhibitors (acetazolamide); early renal failure.
• Others: large volumes of 0.9% saline (dilutional hyperchloraemic acidosis), hypoaldosteronism, and recovery phase of ketoacidosis.

Renal Tubular Acidosis — a Common Examination Topic

The Delta Ratio

Delta ratio = (measured AG − 12) ÷ (24 − measured HCO3⁻)

• < 0.4 — pure normal anion gap acidosis.
• 0.4–0.8 — mixed high and normal anion gap acidosis.
• 1–2 — pure high anion gap acidosis.
• > 2 — coexisting metabolic alkalosis or pre-existing compensated respiratory acidosis.

The osmolar gap (measured minus calculated osmolality, normally < 10) is raised in methanol and ethylene glycol poisoning and is essential when toxic alcohol ingestion is suspected.

Clinical Features

• Respiratory: Kussmaul breathing — deep, sighing, rapid respiration, most marked in diabetic ketoacidosis and uraemia.
• Cardiovascular: impaired myocardial contractility, arteriolar vasodilatation with hypotension, reduced response to catecholamines, and predisposition to arrhythmia. Severe acidaemia (pH < 7.1) is directly cardiotoxic.
• Neurological: confusion, drowsiness, stupor and coma; headache.
• Metabolic: hyperkalaemia from transcellular shift of potassium in exchange for hydrogen ions (marked in inorganic acidosis, less so in ketoacidosis and lactic acidosis); insulin resistance; bone demineralisation in chronic acidosis.
• Features of the underlying cause — the fruity breath of ketosis, the sepsis of lactic acidosis, visual loss in methanol poisoning.

Investigations

• Arterial blood gas with electrolytes
• anion gap with albumin correction
• blood glucose and ketones
• serum lactate
• renal function
• urine pH and urinary anion gap (a positive urinary anion gap suggests renal rather than gastrointestinal bicarbonate loss)
• serum osmolality with calculated osmolar gap
• salicylate and toxic alcohol levels where indicated
• ECG for hyperkalaemic changes.

Management

• Treat the underlying cause — this is the definitive therapy. Insulin and fluids for ketoacidosis; restoration of tissue perfusion, oxygenation and source control for lactic acidosis; antidotes (fomepizole or ethanol) and dialysis for toxic alcohols; and renal replacement therapy in renal failure.
• Restore circulating volume with balanced crystalloid; avoid large volumes of 0.9% saline, which itself causes hyperchloraemic acidosis.
• Correct hyperkalaemia as an urgent priority, and anticipate a fall in potassium as the acidosis corrects and potassium moves back into cells.
• Sodium bicarbonate — remains controversial and is not indicated for most cases. It is generally reserved for severe acidaemia (pH < 7.1) with haemodynamic compromise, for severe hyperkalaemia, and for normal anion gap acidosis with ongoing bicarbonate loss (severe diarrhoea, RTA).
• Dialysis for severe refractory acidosis, particularly with renal failure or dialysable toxins.
• Correct hypocalcaemia and hypophosphataemia as they emerge during treatment.