The electronic balance of negatively charged ions (anions) and positively charged ions (cations) is a constant 1:1 ratio in biological systems. The term anion gap is a bit of a misnomer as there is no true gap in this anion/cation ratio. However, based on the common electrolytes measured in the clinical laboratory, there will still be a positive gap because there are normal amounts of anions in serum that are not measured, and thus the appearance of a calculated gap. If a calculated anion gap is larger than expected (outside of the normal anion gap reference range), it may indicate the presence of a large quantity of anions that are not routinely measured.
Below are two examples of how the anion gap may be calculated:
- [Na+] – [(Cl-) + (HCO3-)]
- [(Na+) + (K+)] – [(Cl-) + (HCO3-)]
In some diseases such as ketoacidosis in patients with uncontrolled diabetes, the amount of negatively charged ions in the form of ketoacids increases. Because these are unmeasured using the aforementioned calculations and the negative ketoacid ions must be balanced with positively charged ions like Na+, the measured amount of anions (Cl- and HCO3-) decreases as part of the electronic balance. This decrease in measured anions and relatively stable amount of cations causes the calculated anion gap to increase above what would be considered a normal range.
Here is a case example of this:
A 47-year-old patient with type I diabetes was found unconscious in the home by a relative and was transported by ambulance to the Emergency Department (ED). Their serum laboratory results were as follows:
- Serum sodium (Na+): 138 mEq/L
- Serum chloride (Cl-): 101 mEq/L
- Serum bicarbonate (HCO3-): 20 mEq/L
- Blood pH: 7.2
- Calculated Anion Gap using equation 1 is
- =[138] – [(101) + (20)]
- =[138] – [121]
- = 17
- The normal reference range for anion gap we will be using for this case is 5 – 12 indicating this patient has an abnormally high anion gap.
This anion gap is significant enough to indicate that other unmeasured anions such as ketoacids are present in this patient's serum. The presence of a decreased blood pH also supports a diagnosis of ketoacidosis.
