Biochemistry · Topic
Anion gap and delta ratio !
The anion gap estimates unmeasured acids and splits metabolic acidoses into two broad groups.
Updated 2026-11-01
Key facts
- AG = Na⁺ − (Cl⁻ + HCO₃⁻). It is mostly albumin, phosphate and sulfate; its normal range depends on the laboratory and analyser.
- Corrected AG: add about 2.5 mmol/L for each 1 g/dL that albumin is below normal (Figge correction).
- High AG (normochloraemic): lactate, ketones, uraemia, methanol, ethylene glycol, salicylates (mnemonic GOLD MARK).
- Normal AG (hyperchloraemic): diarrhoea, renal tubular acidosis, ureterosigmoidostomy, acetazolamide, excess saline.
- Delta ratio = (measured AG − normal AG) / (normal HCO₃⁻ − measured HCO₃⁻): < 1 suggests an added normal-AG acidosis; > 2 suggests an added metabolic alkalosis.
In detail
- Plasma is electrically neutral: measured cations (Na⁺) exceed measured anions (Cl⁻ and HCO₃⁻) because there are unmeasured anions, chiefly albumin.
- When a strong acid and its anion (lactate, β-hydroxybutyrate, formate, glycolate) enter plasma, the H⁺ uses up HCO₃⁻ and the anion stays unmeasured: the AG rises.
- When HCO₃⁻ is lost (stool, urine) the kidney retains Cl⁻ to keep neutrality: HCO₃⁻ falls, Cl⁻ rises and the AG does not change.
- Hypoalbuminaemia (cirrhosis, nephrotic syndrome, malnutrition, critical illness) lowers the AG and can hide a lactic acidosis; that is why it is corrected.
- Causes of a low AG: hypoalbuminaemia, a cationic paraprotein (IgG myeloma), lithium or bromide poisoning (falsely high chloride).
- The delta ratio compares how much the AG rose with how much HCO₃⁻ fell. In a pure high-AG acidosis both change by similar amounts (ratio 1–2); in ketoacidosis it tends towards 1 because ketones are lost in the urine.
Memory aid
GOLD MARK: Glycols, Oxoproline, L-lactate, D-lactate, Methanol, Aspirin, Renal, Ketoacidosis.
- Also called
- AG, Delta–delta
Clinical notes
- GOLD MARK: glycols (ethylene, propylene), oxoproline (chronic paracetamol), L-lactate, D-lactate, methanol, aspirin, renal failure, ketoacidosis.
- In diabetic ketoacidosis treated with large volumes of saline the AG closes but a hyperchloraemic acidosis may remain.
- The AG is calculated from three measured values: an error in any of them (for example Cl⁻) changes it.
Related conditions
- High anion gap metabolic acidosis
- Normal anion gap (hyperchloraemic) metabolic acidosis
- Diabetic ketoacidosis
- Lactic acidosis
Related
- Acid–base interpretation (step by step)
- Serum osmolality and osmolar gap
- Lactate
- β-Hydroxybutyrate
- Serum albumin as a lab test
Test yourself
Think of the answer, then tap the question to see it.
How is the anion gap calculated?
Na⁺ − (Cl⁻ + HCO₃⁻); its normal value depends on the laboratory and it should be corrected when albumin is low.
Why does profuse diarrhoea cause a normal-anion-gap acidosis?
Bicarbonate is lost in stool and the kidney retains chloride to keep neutrality; no unmeasured anion is added.
What does a delta ratio above 2 suggest?
HCO₃⁻ fell less than the AG rose: a metabolic alkalosis (for example from vomiting) coexists.
Why can hypoalbuminaemia hide a lactic acidosis?
Albumin is the main unmeasured anion; when it falls the baseline AG falls, so a 'normal' AG may in fact be raised.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Anion Gap Blood Test: MedlinePlus Medical Test (MedlinePlus, US National Library of Medicine, 2026); Metabolic acidosis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Chloride Blood Test: MedlinePlus Medical Test (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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Representative model, for educational purposes only.