Our bodies need electrolytes — both negatively and positively charged — for multiple functions. The anion gap measures the difference between the positive and negative electrolytes in the blood. An anion gap measurement that is too high or too low indicates a possible problem in the kidneys, lungs, or another part of the body.
Calculating the Anion Gap
The anion gap is the sum of chloride and bicarbonate subtracted from sodium, calculated using the results of a test that measures electrolyte levels in the blood. The normal value varies widely and heavily depends on the person and the accuracy with which the lab analyzes the sample.
The Acid-Base Balance
Maintaining the acid-base balance is essential for the body to function properly. Because it is so important to maintain a pH within a certain range, the body compensates in many ways. The lungs and kidneys play essential roles in maintaining this balance. The lungs’ role is to blow off or retain carbon dioxide, and the kidneys release bicarbonate.
Increased Anion Gap
Many conditions cause an increased anion gap so, in and of itself, a high number is not definitive. For a proper diagnosis, the doctor must also consider the patient’s history, physical exam, and other lab work. Possible precipitating factors to an increased anion gap include drug or alcohol use, renal disease, and diabetes.
Implications of Increased Anion Gap
An increased anion gap may cause poor passage of fluids through tissues, sweet-smelling breath, and a change in mental status. An increased anion gap that appears with a low pH and shock can sometimes indicate lactic acidosis. If the cause of the acidosis is unknown, how large the anion gap is can help determine the cause.
Decreased Anion Gap
A low anion gap is relatively rare. One study suggests this occurs in only 0.8 to three percent in 80,000. Experts attribute this to the fact that the normal range is so large; it takes a lot of factors to get the number to fall below normal. Even when results show a decreased anion gap, it is usually still very close to the normal range.
Implications of Decreased Anion Gap
Because a decreased anion gap is such a rare result, the doctor may repeat the test and order additional testing to arrive at a definitive diagnosis. A decreased anion gap could indicate low albumin, which can be a sign of kidney problems, heart disease, and some forms of cancer.
Laboratory Error
Calculating the anion gap depends on accurate measurement and reporting of multiple electrolytes, including sodium, bicarbonate, and chloride. Due to the number of factors, the results are not always reliable. For example, one study found that in more than 67,000 calculated anion gaps, less than one percent of them were low. Of those, more than 90 percent were due to laboratory error in reporting one of the values.
Albumen
Albumin is the most abundant protein in the blood. Changes in albumin levels can alter the anion gap. One stud showed a direct correlation between changes in albumin concentration and the anion gap, with low albumin translating to a decreased anion gap and high albumin to an increased anion gap. Although low albumin is the second most common cause of low anion gap, it has to be very severe to affect the results.
Other Limitations
Too many charged blood proteins can affect the accuracy of the anion gap. Two medications can also alter the value. Bromide intoxication can result from overuse of certain sedatives, some herbal supplements, and treatments for myasthenia gravis. Lithium toxicity can also cause a decreased anion gap.
Usefulness
The anion gap is useful in identifying metabolic acidosis. An elevated anion gap is a clear indication that a patient needs further examination, but there are some limitations to the test’s effectiveness. Adjustment of the anion gap according to the albumin level should take place in the lab instead of falling to the healthcare team. Determining the patient baseline can also help catch metabolic acidosis early.