NEW Written to fill a gap — raised, normal and low anion gap, the delta ratio, and the osmolar gap.

The anion gap

Raised, normal and low — what each means, the causes, and the two corrections that stop it misleading you.

What it is

AG = Na⁺ − (Cl⁻ + HCO₃⁻), normal 8–12 mmol/L. Some labs add potassium: AG = (Na⁺ + K⁺) − (Cl⁻ + HCO₃⁻), normal 12–16. Know which your lab uses — it shifts the number by about 4.
The unmeasured anions are mostly albumin, with phosphate, sulphate and organic acids.
Its whole purpose is to answer one question in a metabolic acidosis: has bicarbonate been CONSUMED by an acid, or LOST from the body?
- Consumed by an added acid → that acid's anion takes the bicarbonate's place → the gap RISES.
- Lost from gut or kidney → chloride is retained to preserve neutrality → the gap stays NORMAL (a hyperchloraemic acidosis).

Raised anion gap acidosis

An acid has been added. Remember it as KULT or the fuller GOLD MARK.

Letter	Cause	Clue
G	Glycols — ethylene glycol, propylene glycol	Raised osmolar gap; calcium oxalate crystals in urine; antifreeze
O	Oxoproline (pyroglutamic acid)	Chronic paracetamol in a malnourished woman — a genuine exam favourite
L	L-lactate	Shock, sepsis, ischaemic bowel, seizures — the commonest cause by far
D	D-lactate	Short bowel syndrome; not detected by the standard lactate assay
M	Methanol	Raised osmolar gap; visual loss, optic disc oedema
A	Aspirin (salicylate)	Classically a mixed picture — respiratory alkalosis plus raised gap acidosis; tinnitus
R	Renal failure	Retained sulphate, phosphate, urate; raised urea and creatinine
K	Ketoacidosis	Diabetic, alcoholic or starvation; ketones present

The short version, KULT: Ketones · Uraemia · Lactate · Toxins.
If lactate and ketones are normal but the gap is high, think toxins — and go straight to the osmolar gap.
Metformin belongs under lactate; cyanide and carbon monoxide too, via impaired oxidative phosphorylation.

Normal anion gap (hyperchloraemic) acidosis

Bicarbonate has been lost, and chloride has replaced it. Remember it as USED CARP.

Letter	Cause	Note
U	Ureteric diversion (ileal conduit, ureterosigmoidostomy)	Bowel reabsorbs chloride and secretes bicarbonate
S	Saline — large volume 0.9% NaCl	The commonest perioperative cause; a fall in the strong ion difference
E	Endocrine — hyperparathyroidism, Addison's	Aldosterone deficiency impairs H⁺ excretion
D	Diarrhoea	The commonest cause overall — bicarbonate-rich stool
C	Carbonic anhydrase inhibitors — acetazolamide	Renal bicarbonate wasting
A	Addison's disease	With hyperkalaemia and hyponatraemia
R	Renal tubular acidosis	Type 1 distal (can't excrete H⁺, ↓K⁺, stones) · Type 2 proximal (can't reabsorb HCO₃⁻, ↓K⁺, Fanconi) · Type 4 (hypoaldosteronism, ↑K⁺)
P	Pancreatic fistula	Loss of alkaline pancreatic and biliary secretions

Potassium separates the causes

Normal gap acidosis with LOW potassium → diarrhoea, RTA types 1 and 2, acetazolamide, ureteric diversion.
Normal gap acidosis with HIGH potassium → RTA type 4, Addison's, potassium-sparing diuretics, early renal failure.
Urinary anion gap ((Na⁺ + K⁺) − Cl⁻ in urine) separates renal from gut causes: negative means the kidney is excreting NH₄⁺ properly, so the loss is from the gut; positive means the kidney is at fault (RTA). Mnemonic: neg-U-tive = GUT.

LOW anion gap

Much rarer, and nearly always worth a second look — a genuinely low gap usually means a laboratory or paraprotein problem rather than an acid–base one.

Cause	Mechanism
Hypoalbuminaemia	By far the commonest. Albumin is the main unmeasured anion — lose it and the gap falls
Myeloma / paraproteinaemia	IgG paraproteins are cationic, adding unmeasured positive charge
Lithium toxicity	An unmeasured cation
Severe hypercalcaemia or hypermagnesaemia	Unmeasured cations
Bromide or iodide	Falsely raise the measured chloride (pseudohyperchloraemia), so the gap falls
Laboratory error	Always consider it — and severe hypernatraemia or hyperlipidaemia can interfere

The two corrections that stop it misleading you

1 · Correct for albumin — do this every time in a sick patient

Corrected AG = measured AG + 2.5 × (40 − albumin in g/L) / 10
Or simply: add about 2.5 to the gap for every 10 g/L the albumin is below 40.
Worked example: a septic ICU patient with albumin 20 g/L and a measured AG of 12 looks normal. Corrected: 12 + 2.5 × 2 = 17 — a genuinely raised gap that would otherwise have been missed.
This matters enormously in critical illness, where hypoalbuminaemia is near-universal and can mask a lactic acidosis.

2 · The delta ratio — is there a second disorder hiding?

Delta ratio = (measured AG − 12) / (24 − measured HCO₃⁻) — the rise in the gap divided by the fall in bicarbonate.
In a pure raised gap acidosis they should change one-for-one, giving a ratio of about 1.

Ratio	Interpretation
< 0.4	Pure normal gap (hyperchloraemic) acidosis
0.4 – 0.8	Mixed raised and normal gap acidosis — e.g. DKA resuscitated with lots of saline
1 – 2	Pure raised gap acidosis
> 2	A coexisting metabolic ALKALOSIS, or a pre-existing high bicarbonate from chronic respiratory acidosis — the bicarbonate has not fallen as far as it should have

3 · The osmolar gap — when the anion gap is high and unexplained

Calculated osmolarity = 2[Na⁺] + urea + glucose (all in mmol/L).
Osmolar gap = measured − calculated; normal is under 10 mOsm/kg.
A raised osmolar gap AND a raised anion gap points hard at methanol or ethylene glycol — treat with fomepizole or ethanol, plus dialysis.
Ethanol itself raises the osmolar gap without necessarily raising the anion gap.

How to work through a metabolic acidosis

1. Confirm it: low pH, low bicarbonate, negative base excess.
2. Check compensation with Winter's formula: expected PaCO₂ (mmHg) = 1.5 × [HCO₃⁻] + 8 ± 2. A deviation means a second, respiratory disorder.
3. Calculate the anion gap — and correct it for albumin.
4. If raised: check lactate and ketones. If both normal, check renal function, then the osmolar gap for toxic alcohols.
5. If normal: think saline, diarrhoea, RTA. Use potassium and the urinary anion gap to narrow it.
6. Calculate the delta ratio to expose any mixed picture.

Quick recall

AG Na − (Cl + HCO₃)

8–12 without K, 12–16 with

KULT ketones · uraemia · lactate · toxins

USED CARP normal gap

Saline commonest perioperative

Low gap = albumin or myeloma

+2.5 per 10 g/L albumin drop

Delta >2 hidden alkalosis

Osmolar gap toxic alcohols

neg-U-tive urinary AG = gut