Anion gap

INTRODUCTION:

• 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

HIGH ANION GAP ACIDOSIS:

DECREASED ANION GAP IS SEEN IN

• Hypoalbunemia
• Hyponatremia
• Hypothyroidism
• Renal disease
• Hypochloremic acidosis

URINARY ANION GAP:

The urinary anion gap, defined as:

Urinary anion gap = (Na+ + K+) – Cl-

• Urinary Anion Gap (UAG) calculation is useful in cases of Normal Anion Gap (Hyperchloremic) Metabolic Acidosis
• It is useful in evaluating patients with hyperchloremic acidosis. 
• 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.
• 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.
• 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, 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–)
• 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 protein
• Normal anion gap is 10-12 mEq/L