Anion gap explained: high vs normal gap metabolic acidosis
How to calculate the anion gap, why an added acid widens it while bicarbonate loss does not, and how a low albumin can hide a high-gap acidosis.
Chapters (10)
Calculate the serum anion gap, correct it for albumin, and classify a metabolic acidosis as high-gap or normal-gap with its classic causes.
The short version
- The anion gap is Na⁺ − (Cl⁻ + HCO₃⁻), about 8–12 mEq/L by the common definition, but always use your own lab's range.
- A high gap means an added, unmeasured anion: think GOLD MARK.
- A normal gap (hyperchloremic) acidosis means bicarbonate is lost or not regenerated (or chloride is added), and chloride rises in its place.
- Albumin is the biggest unmeasured anion; each 1 g/dL fall lowers the gap by about 2.5, which can hide a high-gap acidosis.
- Corrected gap = measured gap + 2.5 × (4 − albumin in g/dL).
A “normal” anion gap that isn't
The anion gap can mislead. A woman with sepsis and low blood pressure has a sodium of 134, a chloride of 103 and a bicarbonate of 19. Her anion gap is 12. Normal, right?
Not so fast. Her albumin is only 2 g/dL. This lesson shows how to calculate the anion gap, correct it for albumin, and sort a metabolic acidosis into high gap or normal gap.
Electroneutrality: measured and unmeasured ions
Start with one rule: blood is electrically neutral. But a routine panel measures only some of the ions. On the positive side we use sodium; on the negative side, chloride and bicarbonate.[4]
| Cations (positive) | Anions (negative) | |
|---|---|---|
| Measured | Na⁺ | Cl⁻, HCO₃⁻ |
| Unmeasured | mainly K⁺, Ca²⁺, Mg²⁺ | mainly albumin, plus phosphate and sulfate |
Normally there are more unmeasured anions than unmeasured cations. That difference is the anion gap: bookkeeping, not a real hole.[4][3]
Put another way, because cations must equal anions, sodium minus the measured anions equals the unmeasured anions minus the unmeasured cations. The gap is a window onto ions the panel does not report.[4]
The anion gap formula and normal ranges
The common definition, without potassium. All values in mEq/L.
High anion gap metabolic acidosis and GOLD MARK
Picture an acid, HA, entering the blood. Its hydrogen ion is buffered by bicarbonate, so bicarbonate falls. But its anion, A⁻, stays behind, and the lab does not measure it.
Bicarbonate drops, chloride stays put, and the gap gets bigger. That is a high anion gap metabolic acidosis.[3][4]
On paper, the bicarbonate that was used up has been replaced by an anion the panel cannot see, so the sum of chloride and bicarbonate falls while sodium does not.
| Letter | Cause | Note from the lesson |
|---|---|---|
| G | Glycols | ethylene glycol and propylene glycol |
| O | 5-oxoproline | linked to chronic acetaminophen use |
| L | L-lactate | |
| D | D-lactate | seen with short gut syndromes |
| M | Methanol | |
| A | Aspirin | |
| R | Renal failure | |
| K | Ketoacidosis |
GOLD MARK was proposed in 2008 to update older lists such as MUDPILES, adding D-lactate, propylene glycol and 5-oxoproline, and dropping obsolete causes.[8][9][10]
Normal anion gap (hyperchloremic) metabolic acidosis
What if the body loses bicarbonate itself, or the kidney fails to regenerate it, instead of gaining an acid with an unmeasured anion? Then chloride rises to take bicarbonate's place, and the gap stays normal. That is a normal anion gap, or hyperchloremic, metabolic acidosis.[3]
The contrast with a high-gap acidosis is chloride. When an acid with an unmeasured anion is added, chloride stays put and the gap widens. When bicarbonate is lost or not replaced, chloride rises and the gap does not change.
- Diarrhea and other gut losses, such as fistulas
- Renal tubular acidosis
- Acetazolamide
- Urinary diversions into the bowel
- Rapid saline infusion
These are the classic causes covered in the lesson.[5]
Albumin-corrected anion gap
Albumin is the biggest unmeasured anion, so when albumin falls, the gap falls with it. Each 1 g/dL fall in albumin lowers the gap by about 2.5.[6][1] That can hide a high-gap acidosis.[6]
Albumin in g/dL; 4 g/dL is the common normal baseline (some sources use the lab's own normal).[6][7]
- AG = 134 − (103 + 19) = 134 − 122 = 12
- Albumin 2 g/dL: 4 − 2 = 2
- 2.5 × 2 = 5
- Corrected AG = 12 + 5 = 17: her gap is actually high
Uncorrected, her gap of 12 sits inside the common 8–12 range and looks normal. Corrected for an albumin of 2 g/dL, it is 17: a high anion gap metabolic acidosis that the low albumin was hiding.
Practice question
Original · USMLE styleA 67-year-old woman is brought to the emergency department because of fever, cough and confusion for 2 days. Temperature is 39.1°C (102.4°F), pulse is 118/min, respirations are 24/min and blood pressure is 84/50 mm Hg. Crackles are heard over the right lower lung field. She has had no vomiting or diarrhea and takes no medications. Blood samples are drawn before any intravenous fluids are given:
| Arterial blood gas (room air): pH | 7.34 |
|---|---|
| PaCO₂ | 36 mm Hg |
| Serum Na⁺ | 134 mEq/L |
| K⁺ | 4.0 mEq/L |
| Cl⁻ | 103 mEq/L |
| HCO₃⁻ | 19 mEq/L |
| Glucose | 110 mg/dL |
| Creatinine | 1.0 mg/dL |
| Albumin | 2.0 g/dL |
Common questions
How do you calculate the anion gap?
Anion gap = Na⁺ − (Cl⁻ + HCO₃⁻). By this common definition, without potassium, a normal gap is about 8–12 mEq/L, but always use your own lab's range.
What is the normal anion gap with potassium?
Some sources add potassium to the sodium, giving (Na⁺ + K⁺) − (Cl⁻ + HCO₃⁻); the normal range is then about 12–16 mEq/L.
How do you correct the anion gap for albumin?
Corrected gap = measured gap + 2.5 × (4 − albumin in g/dL). Each 1 g/dL fall in albumin lowers the gap by about 2.5.
What does GOLD MARK stand for?
Glycols (ethylene and propylene glycol), 5-oxoproline, L-lactate, D-lactate, methanol, aspirin, renal failure and ketoacidosis: causes of a high anion gap metabolic acidosis.
Why is a normal anion gap acidosis called hyperchloremic?
When bicarbonate is lost (or the kidney fails to replace it, or chloride-rich fluid dilutes it), chloride rises to take its place, so the gap stays normal and chloride is high.
Transcript
Read the full narration, by chapter674 words
0:00A "normal" anion gap that isn't
A woman with sepsis and low blood pressure has a sodium of 134, a chloride of 103, and a bicarbonate of 19. Her anion gap is 12. Normal, right? Not so fast. Her albumin is only 2 g/dL. By the end of this lesson, you'll calculate the anion gap, correct it for albumin, and sort a metabolic acidosis into high gap or normal gap.
0:27Electroneutrality: measured vs unmeasured ions
Start with one rule: blood is electrically neutral. But a routine panel measures only some of the ions. On the positive side, we use sodium. On the negative side, chloride and bicarbonate. The unmeasured cations are mainly potassium, calcium and magnesium. The unmeasured anions are mainly albumin, plus phosphate and sulfate. Normally there are more unmeasured anions than unmeasured cations. That difference is the anion gap: bookkeeping, not a real hole.
1:01The formula and normal ranges (8–12, 12–16 with K+, your lab's range)
Here's the formula: anion gap equals sodium minus, in brackets, chloride plus bicarbonate. Using the common definition, without potassium, a normal gap is about 8 to 12 milliequivalents per litre. Some sources add potassium to the sodium, and then the normal range is about 12 to 16. Many modern analysers report lower values, around 3 to 9 or 3 to 11, so in real life, always use your own lab's range.
1:31High anion gap: how an added acid widens it
Now picture an acid, HA, entering the blood. Its hydrogen ion is buffered by bicarbonate, so bicarbonate falls. But its anion, A−, stays behind, and the lab doesn't measure it. Bicarbonate drops, chloride stays put, and the gap gets bigger. That's a high anion gap metabolic acidosis.
1:54GOLD MARK: causes of a high anion gap
A current mnemonic for the causes is GOLD MARK. G is for glycols: ethylene glycol and propylene glycol. O is for 5-oxoproline, linked to chronic acetaminophen use. L is L-lactate, and D is D-lactate, seen with short gut syndromes. Then M for methanol, A for aspirin, R for renal failure, and K for ketoacidosis. It was proposed in 2008 to update older lists like MUDPILES, adding D-lactate, propylene glycol and 5-oxoproline, and dropping obsolete causes.
2:32Normal anion gap (hyperchloremic) acidosis and its causes
But what if the body loses bicarbonate itself, instead of gaining an acid? Then chloride rises to take bicarbonate's place, and the gap stays normal. That's a normal anion gap, or hyperchloremic, metabolic acidosis. Classic causes are diarrhea and other gut losses like fistulas, renal tubular acidosis, acetazolamide, urinary diversions into the bowel, and rapid saline infusion. One twist: kidney disease can produce either pattern, depending on the situation.
3:05Albumin correction: cAG = AG + 2.5 × (4 − albumin)
Back to albumin, the biggest unmeasured anion: when albumin falls, the gap falls with it. Each 1 g/dL fall in albumin lowers the gap by about 2.5. And that can hide a high gap acidosis. The fix: corrected gap equals measured gap, plus 2.5 times, 4 minus the albumin in grams per decilitre. For our patient: 12, plus 2.5 times 2, equals 17. Her gap is actually high.
3:39Practice question
Your turn. A 67-year-old woman with pneumonia has a blood pressure of 84/50, before any fluids are given. Her pH is 7.34, PaCO2 36, sodium 134, chloride 103, bicarbonate 19, and albumin 2. What's the most likely cause of her metabolic acidosis? A, accumulation of L-lactate. B, bicarbonate loss from the gut. C, type 1 renal tubular acidosis. D, chloride-rich fluids. E, hypoventilation. Pause here and decide. The answer is A. Her measured gap is 12, but corrected it's 17: a high gap acidosis, and in shock, lactate is the classic culprit. B and C cause a normal gap acidosis, and she has no diarrhea. D is out, because she hasn't received any fluids yet. And E is wrong: hypoventilation would raise PaCO2, but hers is below 40, at 36, so she is blowing carbon dioxide off, not keeping it.
4:53High-yield recap
Three things to keep. One: the gap is sodium minus chloride plus bicarbonate, about 8 to 12, but trust your lab. Two: a high gap means an added unmeasured anion, so think GOLD MARK. A normal gap means bicarbonate lost and chloride gained. Three: correct for albumin, adding 2.5 for every g/dL below 4.
5:17Next: Winters' formula
Next up: Winters' formula, and whether her breathing is compensating as much as it should.
Sources
Numbers in the text, e.g. [1], point here- Kraut JA, Nagami GT. The serum anion gap in the evaluation of acid-base disorders: what are its limitations and can its effectiveness be improved? Clin J Am Soc Nephrol 2013;8(11):2018–2024. pmc.ncbi.nlm.nih.gov/articles/PMC3817910/
- Kraut JA, Madias NE. Serum anion gap: its uses and limitations in clinical medicine. Clin J Am Soc Nephrol 2007;2:162–174. doi.org/10.2215/CJN.03020906
- Kharsa A, Vashisht R, Rout P, Meseeha M. Anion Gap and Non-Anion Gap Metabolic Acidosis. StatPearls 2025 (NBK448090). ncbi.nlm.nih.gov/books/NBK448090/
- Lewis JL III. Acid-Base Disorders. MSD Manual Professional (2025). msdmanuals.com/professional/endocrine-and-metabolic-disorders/acid-base-regulation-and-disorders/acid-base-disorders
- Lewis JL III. Metabolic Acidosis. MSD Manual Professional (2025). msdmanuals.com/professional/endocrine-and-metabolic-disorders/acid-base-regulation-and-disorders/metabolic-acidosis
- Figge J, Jabor A, Kazda A, Fencl V. Anion gap and hypoalbuminemia. Crit Care Med 1998;26(11):1807–1810. doi.org/10.1097/00003246-199811000-00019
- Haber LA et al. Evaluating a low anion gap. Cleve Clin J Med 2023;90(10):619–623. ccjm.org/content/90/10/619
- Mehta AN, Emmett JB, Emmett M. GOLD MARK: an anion gap mnemonic for the 21st century. Lancet 2008;372(9642):892. doi.org/10.1016/S0140-6736(08)61398-7
- Duewall JL et al. 5-Oxoproline (pyroglutamic) acidosis associated with chronic acetaminophen use. Proc (Bayl Univ Med Cent) 2010. pmc.ncbi.nlm.nih.gov/articles/PMC2804489/
- Schurmans W, Lemahieu W, Frans E. High anion gap metabolic acidosis: use the proper acronym, discard the red herrings and thou shall find the culprit. Clin Kidney J 2014;7(3):320–322. doi.org/10.1093/ckj/sfu043
The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.
Image credits. Illustrations (blood tube, intestine, nephron, kidney, lungs): Servier Medical Art (smart.servier.com), licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/); adapted (cropped, upscaled, recoloured). Infusion bag: icon by Servier via bioicons.com, CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/); adapted (recoloured). All diagrams, formulas and animation: original (Medservatory). Previous: EP 01 · ABG basics. Next: EP 03 · Winters' formula.
Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-REN-002.
For exam study only, not medical advice. Read the medical disclaimer.
In this series
Playlist on YouTube- EP 01ABG interpretation, made simple5:35
- EP 02Anion gap explained: high vs normal gap metabolic acidosis5:25
- EP 03Winters' formula: the expected PaCO₂ in metabolic acidosis5:10
- EP 04Delta ratio: find the hidden second acid–base disorder5:09
- EP 05New bicarbonate: how the kidney excretes acid with ammonium5:23
- EP 06High anion gap metabolic acidosis causes, sorted by the anion5:54
- EP 07Osmolar gap: how toxic alcohols hide from the anion gap5:31
- EP 08Urine anion gap: telling diarrhea from RTA5:33
- EP 09Renal tubular acidosis: tell RTA types 1, 2 and 4 apart5:24
- EP 10Metabolic alkalosis: generation, maintenance and urine chloride5:30
- EP 11Vomiting metabolic alkalosis: why the urine turns acid5:36
- EP 12Bartter vs Gitelman: NKCC2, NCC and urine calcium5:21
- EP 13Respiratory acidosis compensation: acute vs chronic5:22
- EP 14Respiratory alkalosis compensation: acute vs chronic5:33
- EP 15Metabolic alkalosis compensation: the expected PaCO₂5:12
- EP 16Salicylate poisoning acid-base: a classic mixed disorder5:31
- EP 17Type A vs type B lactic acidosis: split it by mechanism5:33
- EP 18DKA anion gap explained: from high gap to hyperchloraemic acidosis5:42
- EP 19Acidosis and hyperkalemia: how pH shifts potassium5:43
- EP 20ABG interpretation in 6 steps: the acid-base algorithm5:32
- EP 21Acid-base practice cases: three ABG vignettes, one algorithm5:44