Anion Gap

  • Represents those unmeasured anions in plasma (normally 10 to 12 mmol/L)
  • AG = Na+ – (Cl- + HCO3-)
  • The unmeasured anions include anionic proteins (albumin), phosphate, sulfate, and organic anions
  • Normal anion gap depends on serum phosphate and serum albumin
  • Normal AG = 0.2 x [albumin] (g/L) + 1.5 x [phosphate] (mmol/L)
  • Albumin is the major unmeasured anion and contributes a major of the value of the anion gap
  • A decrease in the AG can be due to
  1. ↑ in unmeasured cations (calcium, magnesium, potassium)
  2. Addition abnormal cations, such as lithium (lithium intoxication) or cationic immunoglobulins (plasma cell dyscrasias) to the blood
  3. ↓in the major plasma anion albumin concentration (nephrotic syndrome)
  4. ↓ in the effective anionic charge on albumin by acidosis
  5. Hyperviscosity and severe hyperlipidemia, which can lead to an underestimation of sodium and chloride concentrations
  • A fall in serum albumin by 1 g/dL from the normal value (4.5 g/dL) decreases the AG by 2.5 mEq/L
Lactic acidosis
Respiratory failure
CO, cyanide
Cholera, malaria
Drugs/toxins: Biguanides, INH
Renal failure
Renal Tubular Acidosis
Ethylene glycol, propylene glycol
Ethanol, Methanol

  • Hypoalbunemia
  • Hyponatremia
  • Hypothyroidism
  • Renal disease
  • Hypochloremic acidosis
  • The urinary anion gap, defined as:
Urinary anion gap = (Na+ + K+) – Cl-
  1. It is useful in evaluating patients with hyperchloremic acidosis. 
  2. The test provides an approximate index to urinary NH4+ excretion, as measured by a negative urinary anion gap, that is, urinary (Na+ + K+) is less than urinary CI-. Thus, in hyperchloremic metabolic acidosis, a normal renal response would be a negative urinary anion gap, generally in the range of 30 to 50 mEq per liter.
  3. In such an instance, the hyperchloremic acidosis is probably due to gastrointestinal losses rather than a renal lesion. In contrast, a positive urinary anion gap implies a renal tubular disorder.
  • Urinary Anion Gap (UAG) calculation is useful in cases of Normal Anion Gap (Hyperchloremic) Metabolic Acidosis
  • Normal Anion Gap Acidosis may result from excessive bicarbonate losses from either the gastrointestinal tract (eg diarrhea, cholera) or renal sources (eg Renal Tubular Acidosis)
  • Urinary Anion Gap Estimation helps to distinguish Renal bicarbonate loss from Gastrointestinal bicarbonate loss thereby helping in establishing the cause of normal anion gap metabolic acidosis
Positive Urinary Anion Gap:
  • - Implies Renal loss of Bicarbonate and the diagnosis is usually distal RTA
Negative Urinary Anion Gap:
  • - Implies Gastrointestinal loss of Bicarbonate
Exam Question
  • High Anion Gap Acidosis is seen in Renal Tubular Acidosis
  • High Anion Gap Acidosis is seen in Diabetic Ketoacidosis,Lactic Acidosis, Methanol Poisoning
  • Starvation, Ethylene glycol poisoning are causes of increased anion gap
  • The anion gap is calculated as AG = Na+ – (Cl- + HCO3-)
  • A 30 year old presents with nausea, weakness, headache and impaired vision and high anion gap metabolic acidosis is diagnosed to have Methanol
  • Urinary anion gap is an indication of excretion of NH4+
  • Cholera & Diarrhoea is associated with normal anion gap metabolic acidosis
  • Renal tubular Acidosis is diagnosed using a positive urinary anion gap
  • Anion gap is mostly due to protien
  • Normal anion gap is 10-12 mEq/L

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