High & Low Anion Gap Acidosis List

TL;DR

For MRCP Part 1, recognising the List: Causes of High/Low Anion Gap Acidosis is essential because acid–base disorders are frequently tested in both physiology and clinical medicine questions. The key distinction is whether unmeasured anions are accumulating (high anion gap metabolic acidosis) or bicarbonate is being lost/replaced by chloride (normal or low anion gap metabolic acidosis). Memorising common causes, understanding the underlying mechanism, and avoiding common calculation errors will significantly improve examination performance.

Why this matters

Acid–base interpretation is a core competency assessed throughout MRCP Part 1. Candidates are expected to calculate the anion gap, identify the underlying disorder and relate it to common clinical presentations.

Rather than simply memorising mnemonics, successful candidates understand why the anion gap changes. This allows rapid interpretation of arterial blood gases (ABGs), electrolyte panels and clinical scenarios.

The classic equation is:

Anion Gap = Na⁺ − (Cl⁻ + HCO₃⁻)

A normal anion gap is generally 8–12 mmol/L (without potassium), although laboratory reference ranges vary slightly.

Understanding the anion gap

The anion gap represents the concentration of unmeasured anions in plasma.

Examples include:

• Albumin

• Phosphate

• Sulphate

• Organic acids

• Lactate

• Ketones

When these accumulate, the anion gap increases.

If bicarbonate is lost but replaced by chloride, the gap remains normal despite metabolic acidosis.

The 5 most tested subtopics

1. High anion gap metabolic acidosis (HAGMA)

This occurs when excess acids accumulate in the bloodstream.

The modern mnemonic is GOLD MARK, replacing older mnemonics such as MUDPILES.

Cause	Clinical example	Mechanism
G Glycols	Ethylene glycol, propylene glycol	Toxic metabolites
O Oxoproline	Chronic paracetamol use	Pyroglutamic acidosis
L L-lactate	Septic shock, hypoxia	Lactic acidosis
D D-lactate	Short bowel syndrome	Bacterial metabolism
M Methanol	Toxic alcohol ingestion	Formic acid production
A Aspirin	Salicylate poisoning	Mixed acid-base disorder
R Renal failure	Advanced CKD	Sulphate and phosphate retention
K Ketoacidosis	Diabetic, alcoholic or starvation	Ketone accumulation

These causes account for the vast majority of MRCP examination questions.

2. Normal (hyperchloraemic) anion gap metabolic acidosis

These disorders involve loss of bicarbonate rather than accumulation of organic acids.

Common causes include:

1. Diarrhoea

2. Pancreatic fistula

3. Ileostomy

4. Renal tubular acidosis

5. Acetazolamide

6. Early renal failure

7. Ureteric diversion

8. Excess saline infusion

Here chloride rises as bicarbonate falls, keeping the anion gap within the reference range.

3. Renal tubular acidosis (RTA)

RTA is frequently examined because candidates must distinguish the different subtypes.

Type 1 (Distal)

• Failure of hydrogen ion secretion

• Urine remains alkaline

• Kidney stones

• Hypokalaemia

Type 2 (Proximal)

• Impaired bicarbonate reabsorption

• Often associated with Fanconi syndrome

• Hypokalaemia

Type 4

• Hypoaldosteronism

• Hyperkalaemia

• Common in diabetic nephropathy

Remember:

Type 4 = Hyperkalaemia

This association is repeatedly tested.

4. Correcting the anion gap for albumin

Albumin is the major unmeasured anion.

Hypoalbuminaemia may mask a significant high anion gap acidosis.

Correction:

Corrected AG = Measured AG + 2.5 × (4 − serum albumin in g/dL)

This concept appears regularly in nephrology and intensive care questions.

5. Mixed acid–base disorders

Not every patient has a single abnormality.

Examples include:

• Salicylate poisoning

• Septic shock

• Diabetic ketoacidosis with vomiting

• Chronic kidney disease with respiratory compensation

Candidates should always ask:

• Does the anion gap fit?

• Is respiratory compensation appropriate?

• Could there be more than one disorder?

High-yield causes to remember

High anion gap metabolic acidosis

• Lactic acidosis

• Diabetic ketoacidosis

• Alcoholic ketoacidosis

• Starvation ketosis

• Methanol poisoning

• Ethylene glycol poisoning

• Salicylate poisoning

• Chronic kidney disease

• D-lactic acidosis

• Pyroglutamic (oxoproline) acidosis

Normal anion gap metabolic acidosis

• Diarrhoea

• Renal tubular acidosis

• Acetazolamide

• Pancreatic drainage

• Ileostomy

• Ureterosigmoidostomy

• Early renal insufficiency

• Excess intravenous saline

Practical study-tip checklist

✓ Memorise GOLD MARK rather than older mnemonics.

✓ Always calculate the anion gap before interpreting the ABG.

✓ Remember that hypoalbuminaemia lowers the measured gap.

✓ Learn the distinguishing features of all RTA types.

✓ Associate diabetic ketoacidosis with high anion gap.

✓ Associate diarrhoea with normal anion gap.

✓ Know which poisonings produce HAGMA.

✓ Practise interpreting ABGs under timed conditions.

✓ Compare electrolyte patterns rather than relying on symptoms alone.

✓ Review common compensation formulas after mastering the anion gap.

Practical examples / mini-cases

Mini-case

A 24-year-old man presents with polyuria, vomiting and abdominal pain.

Investigations:

• Glucose: 31 mmol/L

• pH: 7.12

• HCO₃⁻: 8 mmol/L

• Na⁺: 138 mmol/L

• Cl⁻: 96 mmol/L

Question

What acid–base disturbance is present?

Answer

High anion gap metabolic acidosis.

Explanation

Anion gap = 138 − (96 + 8)

= 34 mmol/L

The markedly elevated gap together with hyperglycaemia strongly suggests diabetic ketoacidosis.

For MRCP Part 1, remember that ketoacids increase unmeasured anions while bicarbonate falls.

Common pitfalls (5 bullets)

• Forgetting to correct the anion gap in hypoalbuminaemia.

• Using outdated mnemonics without recognising newer causes such as oxoproline.

• Assuming all metabolic acidosis is due to sepsis.

• Confusing diarrhoea (normal gap) with lactic acidosis (high gap).

• Forgetting that salicylate poisoning often causes a mixed respiratory alkalosis and metabolic acidosis.

FAQs

1. What is the normal anion gap?

Most laboratories report a normal range of approximately 8–12 mmol/L when potassium is excluded. Always use the laboratory's reference interval where provided.

2. Which mnemonic is preferred for MRCP Part 1?

GOLD MARK is considered the modern and more comprehensive mnemonic because it includes newer recognised causes such as oxoproline and D-lactic acidosis.

3. Why does diarrhoea not increase the anion gap?

Diarrhoea causes bicarbonate loss from the gastrointestinal tract. Chloride increases to maintain electroneutrality, producing a normal (hyperchloraemic) anion gap metabolic acidosis.

4. Why should albumin be considered?

Albumin is the major unmeasured plasma anion. Low albumin reduces the measured anion gap and may conceal clinically important high anion gap acidosis.

5. Which poisonings are commonly examined?

Methanol, ethylene glycol and salicylate poisoning are classic MRCP Part 1 favourites because they produce characteristic high anion gap metabolic acidosis with distinctive clinical clues.

Ready to start?

Understanding the anion gap is only one part of mastering acid–base disorders. Strengthen your examination performance by reviewing the MRCP Part 1 overview, practising hundreds of Free MRCP MCQs, attempting a full-length mock test, and reinforcing difficult concepts through our MRCP lectures. Regular practice with real examination-style questions is the most effective way to recognise acid–base patterns rapidly under exam conditions.

Sources

1. MRCP(UK). https://www.mrcpuk.org/

2. KDIGO Clinical Practice Guidelines for Kidney Disease. https://kdigo.org/

3. Kraut JA, Madias NE. Serum Anion Gap: Its Uses and Limitations in Clinical Medicine. Clinical Journal of the American Society of Nephrology.

4. Oh MS, Carroll HJ. Disorders of Acid–Base Balance. New England Journal of Medicine.

5. Oxford Handbook of Clinical Medicine. Latest edition.