What is the anion gap formula?

The anion gap is calculated using the formula: Anion Gap = Sodium (Na+) - [Chloride (Cl-) + Bicarbonate (HCO3-)]. The normal range is 8-12 mEq/L (some labs use 3-11 mEq/L). When albumin is below normal, an albumin-corrected anion gap should be calculated: Corrected AG = Measured AG + 2.5 × (4 - measured albumin in g/dL).

What is a normal anion gap?

The normal anion gap is 8-12 mEq/L using the traditional formula (Na - Cl - HCO3). Some laboratories report a normal range of 3-11 mEq/L when potassium is included in the calculation. An anion gap above 12 mEq/L is generally considered elevated and may indicate high anion gap metabolic acidosis. The normal value may vary slightly between laboratories.

What is the delta-delta ratio?

The delta-delta ratio (also called delta gap or delta-delta) helps identify mixed acid-base disorders. It is calculated as: (Measured AG - Normal AG) / (Normal HCO3 - Measured HCO3). A ratio of 1-2 suggests pure high anion gap metabolic acidosis. A ratio below 1 suggests a concurrent normal anion gap metabolic acidosis. A ratio above 2 suggests a concurrent metabolic alkalosis. It is most useful when the anion gap is elevated.

Why do you correct the anion gap for albumin?

Albumin is a negatively charged protein that contributes to the anion gap. When albumin is low (hypoalbuminaemia, common in hospitalised patients), the measured anion gap is artificially low. A patient with true high anion gap metabolic acidosis may have a normal-appearing anion gap if they are hypoalbuminaemic. The Figge correction adjusts: for every 1 g/dL decrease in albumin below 4 g/dL, add 2.5 mEq/L to the measured anion gap.

What is normal anion gap metabolic acidosis?

Normal anion gap metabolic acidosis (also called hyperchloraemic metabolic acidosis) occurs when bicarbonate is lost or acid is retained but chloride increases to maintain electroneutrality. Causes are remembered by HARDUPS: Hyperalimentation, Addison disease, Renal tubular acidosis, Diarrhoea, Ureteral diversions, Pancreatic fistula, Saline infusion (excess). The most common cause is diarrhoea, followed by renal tubular acidosis.

What is the difference between anion gap and osmolar gap?

The anion gap measures the difference between unmeasured cations and anions in the blood, reflecting accumulation of organic acids. The osmolar gap measures the difference between measured and calculated serum osmolarity, reflecting unmeasured osmotically active substances such as methanol, ethylene glycol, or ethanol. Both are often calculated together when toxic alcohol ingestion is suspected, as toxic alcohols can elevate both gaps.

Anion Gap Calculator | Standard, Corrected & Delta-Delta

Enter Electrolyte Values

Sodium (Na⁺)

mEq/L

Normal: 136–145

Chloride (Cl⁻)

mEq/L

Normal: 98–106

Bicarbonate (HCO₃⁻)

mEq/L

Normal: 22–29

AG = Na⁺ − (Cl⁻ + HCO₃⁻) = Enter values above

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Optional Values (for Corrected AG & Delta-Delta)

Serum Albumin

g/dL

For albumin-corrected AG (Figge correction). Leave blank if normal.

Normal: 3.5–5.0

Potassium (K⁺) — optional

mEq/L

Some formulas include K⁺ in AG calculation

Normal: 3.5–5.0

Units System

mEq/L and mmol/L are numerically equivalent for monovalent ions

Normal AG Reference

Use your lab's reference range for most accurate interpretation

Anion Gap

—

mEq/L

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Anion Gap on Clinical Scale

Normal (<12)Mildly ↑Moderately ↑Severely ↑

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🔬 MUDPILES — High Anion Gap Causes

Differential diagnosis for elevated anion gap metabolic acidosis. Most highlighted causes are most common in clinical practice.

🚨 Clinical note: The most common causes in practice are lactic acidosis, diabetic ketoacidosis (DKA), and renal failure. Always consider methanol and ethylene glycol poisoning in unexplained high anion gap, especially if the osmolar gap is also elevated.

📋 HARDUPS — Normal Anion Gap Causes

Differential diagnosis for normal (hyperchloraemic) anion gap metabolic acidosis.

💡 Key point: In normal anion gap metabolic acidosis, bicarbonate is lost (or acid is gained) and chloride rises to maintain electroneutrality. The most common cause is diarrhoea, followed by renal tubular acidosis.

📐 Delta-Delta Ratio — Mixed Disorder Detection

Delta-Delta (Δ-Δ) Ratio

Δ-Δ = (Measured AG - Normal AG) / (Normal HCO₃ - Measured HCO₃)

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Enter values and calculate to see delta-delta interpretation.

<1.0

Mixed high AG + normal AG metabolic acidosis

1.0–2.0

Pure high anion gap metabolic acidosis

>2.0

High AG metabolic acidosis + concurrent metabolic alkalosis

⚠️ Delta-delta is only meaningful when the anion gap is elevated. If the anion gap is normal, the delta-delta calculation is not clinically applicable.

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Content reviewed against Rose & Post clinical physiology references, Kraut & Madias NEJM acid-base review, and UpToDate metabolic acidosis guidelines. Last updated: July 2026.

What Is the Anion Gap?

The anion gap (AG) is a calculated value representing the difference between unmeasured anions and unmeasured cations in plasma. It is calculated using the formula: AG = Na⁺ − (Cl⁻ + HCO₃⁻). The normal range is 8–12 mEq/L (some laboratories use 3–11 mEq/L). An elevated anion gap indicates the presence of unmeasured anions — most commonly organic acids — and is a key clinical tool for diagnosing and categorising metabolic acidosis.

The anion gap exploits a fundamental principle of chemistry: electrical neutrality. In any solution, the total positive charges must equal the total negative charges. In plasma, the major measured cation is sodium (Na⁺), and the major measured anions are chloride (Cl⁻) and bicarbonate (HCO₃⁻). The gap between them represents unmeasured anions (albumin, phosphate, sulphate, organic acids) minus unmeasured cations (calcium, magnesium, potassium). When pathological acids accumulate in the blood, they displace bicarbonate and widen the anion gap.

The Anion Gap Formula

Standard: AG = Na⁺ − (Cl⁻ + HCO₃⁻) Normal range: 8–12 mEq/L With potassium: AG = (Na⁺ + K⁺) − (Cl⁻ + HCO₃⁻) Normal range: 10–16 mEq/L (if K⁺ included) Albumin-corrected (Figge): Corrected AG = AG + 2.5 × (4.0 − albumin g/dL)

Albumin Correction — Why It Matters

Albumin is negatively charged and contributes approximately 2.5 mEq/L to the anion gap for every 1 g/dL of albumin. A normal albumin of 4 g/dL contributes approximately 10 mEq/L to the anion gap. When albumin is low — as it frequently is in critically ill, hospitalised patients — the measured anion gap is artificially reduced.

A patient with sepsis, liver disease, malnutrition, or nephrotic syndrome may have an albumin of 2 g/dL, causing the measured anion gap to be up to 5 mEq/L lower than the true value. This means a true high anion gap metabolic acidosis could be masked by a normal-appearing anion gap. The Figge albumin correction — adding 2.5 × (4 − measured albumin) to the measured AG — corrects for this, revealing the true anion gap.

MUDPILES — High Anion Gap Differential

When the anion gap is elevated, a systematic approach to differential diagnosis is essential. The MUDPILES mnemonic covers the major causes of high anion gap metabolic acidosis:

M — Methanol: Toxic alcohol ingestion causing formic acid accumulation. Often accompanied by elevated osmolar gap. Visual symptoms (scotoma, blindness) are characteristic.
U — Uraemia (renal failure): Accumulation of sulphate, phosphate, and organic anions in chronic kidney disease. One of the most common causes of high AG in hospitalised patients. Check with our Kidney Function Calculator.
D — Diabetic Ketoacidosis (DKA): Accumulation of acetoacetate and beta-hydroxybutyrate. Glucose typically very elevated. Common in Type 1 diabetics and increasingly in Type 2. Monitor blood glucose with our Blood Sugar Checker.
P — Propylene glycol / Paracetamol (acetaminophen): Propylene glycol (used in IV medications) causes lactic acidosis. Paracetamol toxicity causes fulminant hepatic failure with lactate elevation.
I — Isoniazid / Iron: Isoniazid prevents GABA synthesis and causes lactic acidosis in overdose. Iron toxicity causes mitochondrial failure and lactic acidosis.
L — Lactic acidosis: The most common cause of elevated anion gap in the ICU. Type A (tissue hypoperfusion: sepsis, shock, cardiac failure) or Type B (metformin, liver failure, malignancy). Always consider in any acutely unwell patient.
E — Ethylene glycol: Antifreeze ingestion causing glycolic acid and oxalic acid accumulation. Associated with oxalate crystals in urine and renal failure. Osmolar gap typically elevated early.
S — Salicylates: Aspirin overdose causes a mixed disorder — initially respiratory alkalosis followed by high anion gap metabolic acidosis. High suspicion needed in overdose scenarios.

HARDUPS — Normal Anion Gap Differential

Normal anion gap metabolic acidosis (hyperchloraemic acidosis) occurs when bicarbonate is lost directly or acid is retained while chloride rises to maintain electroneutrality. The mnemonic HARDUPS captures the major causes:

H — Hyperalimentation: Total parenteral nutrition can cause hyperchloraemic acidosis through amino acid metabolism.
A — Addison's disease: Aldosterone deficiency causes hyperkalaemia and normal anion gap acidosis (Type IV RTA).
R — Renal tubular acidosis (RTA): Failure of the renal tubules to excrete acid or reabsorb bicarbonate. Types I, II, and IV all cause normal anion gap acidosis.
D — Diarrhoea: The most common cause of normal anion gap metabolic acidosis. Intestinal secretions contain large amounts of bicarbonate; profuse diarrhoea causes significant bicarbonate loss.
U — Ureteral diversions: Ureterosigmoidostomy and ileal conduit procedures expose the bowel to urine, with chloride absorption and bicarbonate secretion causing acidosis.
P — Pancreatic fistula: Pancreatic secretions are bicarbonate-rich; fistulae cause direct bicarbonate loss.
S — Saline infusion: Large volumes of normal saline cause dilutional hyperchloraemic acidosis. Important in surgical and critically ill patients receiving aggressive IV fluid resuscitation.

The Delta-Delta Ratio — Detecting Mixed Disorders

When the anion gap is elevated, the delta-delta ratio helps determine whether additional acid-base disorders are present. It compares the rise in anion gap to the fall in bicarbonate:

Δ-Δ = (Measured AG − Normal AG) / (Normal HCO₃ − Measured HCO₃) Normal AG = 12, Normal HCO₃ = 24 Δ-Δ < 1.0 → Mixed HAGMA + normal AG metabolic acidosis Δ-Δ 1.0–2.0 → Pure high anion gap metabolic acidosis Δ-Δ > 2.0 → HAGMA + concurrent metabolic alkalosis

The clinical logic: in a pure high anion gap metabolic acidosis, for every 1 mEq/L rise in anion gap, bicarbonate should fall by approximately 1 mEq/L. If bicarbonate has fallen more than expected (ratio below 1), there is an additional process consuming bicarbonate (concurrent normal AG acidosis). If bicarbonate has fallen less than expected (ratio above 2), something is protecting the bicarbonate — likely a concurrent metabolic alkalosis from vomiting, diuretics, or nasogastric suction.

⚕️ Clinical Disclaimer: This calculator is for educational and reference purposes only. Acid-base disorders require clinical correlation with the patient's history, examination, arterial blood gas, and additional investigations. Do not make clinical decisions based on calculated values alone without appropriate medical assessment.

Frequently Asked Questions

AG = Na⁺ − (Cl⁻ + HCO₃⁻). Normal range: 8–12 mEq/L. With albumin correction: Corrected AG = AG + 2.5 × (4 − albumin g/dL). Some labs include K⁺, giving a normal range of 10–16 mEq/L.

Normal anion gap is 8–12 mEq/L (traditional) or 3–11 mEq/L (modern labs with improved chloride assays). Above 12 mEq/L is elevated. The exact threshold varies by laboratory — always use your lab's reference range.

MUDPILES: Methanol, Uraemia (renal failure), DKA, Propylene glycol/Paracetamol, Isoniazid/Iron, Lactic acidosis, Ethylene glycol, Salicylates. Most common in practice: lactic acidosis, DKA, and renal failure.

Δ-Δ = (AG − 12) / (24 − HCO₃). Below 1: mixed HAGMA + normal AG acidosis. 1–2: pure HAGMA. Above 2: HAGMA + metabolic alkalosis. Only useful when AG is elevated.

Albumin contributes ~2.5 mEq/L per g/dL to the anion gap. Low albumin (common in sick patients) artificially lowers the measured AG, potentially masking true HAGMA. Corrected AG = AG + 2.5 × (4 − albumin).

HARDUPS: Hyperalimentation, Addison's, Renal tubular acidosis, Diarrhoea, Ureteral diversions, Pancreatic fistula, Saline infusion. Bicarbonate is lost and chloride rises to compensate. Most common cause: diarrhoea.

Anion gap measures unmeasured ions (organic acids). Osmolar gap = measured osmolarity − calculated osmolarity, reflecting unmeasured osmotically active substances (methanol, ethylene glycol, ethanol). Both are elevated in toxic alcohol ingestion.

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