Question 1

What is the anion gap formula?

Accepted Answer

Anion Gap (mEq/L) = Sodium − (Chloride + Bicarbonate). Normal range: 8–12 mEq/L (using modern ion-selective electrode analysers). Older laboratories using flame photometry may have a normal range of 12 ± 4 mEq/L. A value above the upper limit of normal indicates unmeasured anions and suggests a high anion gap metabolic acidosis (HAGMA).

Question 2

Why does the anion gap need albumin correction?

Accepted Answer

Albumin is the main unmeasured anion in plasma. Low albumin (hypoalbuminaemia) falsely lowers the anion gap, potentially masking a true high anion gap metabolic acidosis. The correction: Corrected AG = Calculated AG + 2.5 × (4.0 − Albumin g/dL). For every 1 g/dL drop in albumin below 4.0, add 2.5 to the anion gap.

Question 3

What is the delta ratio and how is it interpreted?

Accepted Answer

The delta ratio (Δ/Δ) detects mixed acid-base disorders when a high anion gap metabolic acidosis is present. Formula: (AG − 12) ÷ (24 − HCO₃). Interpretation: <0.4 — pure non-gap metabolic acidosis (AG elevation not explained by HAGMA); 0.4–1.0 — combined HAGMA + non-gap metabolic acidosis; 1.0–2.0 — pure HAGMA (expected); >2.0 — HAGMA with concurrent metabolic alkalosis (HCO₃ higher than expected).

Question 4

What are the causes of high anion gap metabolic acidosis (MUDPILES)?

Accepted Answer

MUDPILES mnemonic: Methanol; Uraemia (renal failure); Diabetic ketoacidosis (DKA); Propylene glycol / Paracetamol (acetaminophen) toxicity; Isoniazid / Iron overdose; Lactic acidosis (type A — hypoperfusion; type B — metformin, liver failure); Ethylene glycol; Salicylate toxicity.

Question 5

What are the causes of normal anion gap metabolic acidosis (HARDUPS)?

Accepted Answer

HARDUPS mnemonic: Hyperalimentation (TPN); Addison's disease; Renal tubular acidosis (RTA types 1, 2, 4); Diarrhoea (GI bicarbonate loss — most common cause globally); Ureteroenteric fistula / ileal conduit; Pancreatic fistula; Saline excess (hyperchloraemic acidosis).

Question 6

What is Winter's formula for metabolic acidosis?

Accepted Answer

Winter's formula predicts the expected respiratory compensation in primary metabolic acidosis: Expected pCO₂ = (1.5 × HCO₃) + 8 ± 2. If the measured pCO₂ is higher than expected, there is a concurrent respiratory acidosis. If lower, there is a concurrent respiratory alkalosis. This formula requires ABG values.

Question 7

What is the normal anion gap?

Accepted Answer

Using modern ion-selective electrodes: normal anion gap is 8–12 mEq/L. Older methods (flame photometry): 12 ± 4 mEq/L. The normal value also depends on albumin — the commonly stated 'normal 12' assumes albumin of 4.0 g/dL. Always correct for albumin. An albumin-corrected AG >12 mEq/L is abnormally elevated.

Question 8

Can the anion gap be negative?

Accepted Answer

A very low or negative anion gap is rare but clinically significant. Causes include: severe hypoalbuminaemia (reduced unmeasured anions), hyperparaproteinaemia (e.g. multiple myeloma — cationic paraproteins), hypercalcaemia/hypermagnesaemia, bromide or iodide intoxication (interfering with chloride measurement), and laboratory error. Always check albumin and consider paraprotein if AG is unexpectedly low.

Delta Ratio	Interpretation
< 0.4	Pure non-gap metabolic acidosis (no HAGMA contribution)
0.4 – 1.0	Combined HAGMA + non-gap metabolic acidosis (mixed)
1.0 – 2.0	Pure HAGMA — expected range
> 2.0	HAGMA + concurrent metabolic alkalosis (HCO₃ higher than expected)

Anion Gap Calculator — With Albumin Correction & Delta Ratio | Mixed Acid-Base

1Formulas

2Causes of Metabolic Acidosis

🔴 HAGMA — MUDPILES Mnemonic

🟢 NAGMA — HARDUPS Mnemonic

3Delta Ratio Interpretation

4Frequently Asked Questions