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Anion Gap
(September 2002)
(Download 
Anion Gap.pdf)
What is it?
Anion gaps are a consequence of our inability to routinely measure all the ions present in blood. In reality the sum of all positive ions (cations) and the sum of all negative ions (anions) is equal but in practice we do not measure all the major anion species. Many proteins, most notably albumin carry significant numbers of negative charges and other compounds like sulfates are difficult to measure. Despite this, anion gaps are useful tools because they can help differentiate metabolic acidoses and even unmask certain types of myeloma.
| Major Cations | mEq/L | Major Anions | mEq/L |
|---|
| Total |
150 |
Total |
150 |
| Na+ |
140 |
Cl- |
100 |
| K+ |
4 |
HCO3- |
27 |
| Ca2+ |
4.5 |
Protein- |
15 |
| Mg2+ |
1.5 |
PO43- |
2 |
|
|
SO42- |
1 |
|
|
Organic acids |
5 |
The normal anion gap is approximately 7 - 17 mmol/L.
What is the clinical significance of a high anion gap?
There are three possible causes of a raised anion gap, increased unmeasured anions circulating in the blood (usually a metabolic acidosis), decreased unmeasured cations (e.g. hypocalcaemia), and laboratory error.
- Increased unmeasured anions
- Ketones - Diabetic ketoacidosis, starvation ketosis, alcoholic ketosis
- Acetate
- Lactic acidosis - Type A (with tissue hypoxia - shock or severe CCF) and Type B (without tissue hypoxia - biguanide oral hypoglycaemics, convulsions)
- Renal failure - provided the creatinine is > 0.35 mmol/L
- Ingestion - salicylate (aspirin), volatile alcohols (Methanol, Ethylene glycol), paraldehyde
- Decreased unmeasured cations
- Hypocalcaemia - low Vitamin D, malabsorption.
- hypomagnesaemia (rare)
- Laboratory error
What is the clinical significance of a low anion gap?
There are three possible causes of a decreased anion gap, decreased unmeasured anions circulating in the blood (usually low protein, especially hypoalbuminaemia), increased unmeasured cations (e.g. hypercalcaemia or an atypical IgG myeloma cation), and laboratory error.
- Decreased unmeasured anions
- Severe Hypoalbuminaemia
- Nephrotic syndrome
- Protein-losing enteropathy
- Exfoliative dermatitis
- Malnutrition
- Increased unmeasured cations
- Hypercalcaemia - hyperparathyroidism, malignancy, excess Vitamin D
- Hypermagnesaemia (rare)
- Increased unusual cations
- Atypical IgG myeloma proteins
- Laboratory error
About the Author
This HAPS Communique was written by Dr Phil Tynan , Former Director of Clinical Chemistry.
Clinical Chemistry Contacts
Dr Huy Tran - Director - 49214005
Professor Geoffrey Kellerman - 49214000
Clinical Chemistry Laboratory - 49214405