Serum Anion Gap

Abstract

The serum anion gap, calculated from the electrolytes measured in the chemical laboratory, is defined as the sum of serum chloride and bicarbonate concentrations subtracted from the serum sodium concentration. This entity is used in the detection and analysis of acid-base disorders, assessment of quality control in the chemical laboratory, and detection of such disorders as multiple myeloma, bromide intoxication, and lithium intoxication. The normal value can vary widely, reflecting both differences in the methods that are used to measure its constituents and substantial interindividual variability. Low values most commonly indicate laboratory error or hypoalbuminemia but can denote the presence of a paraproteinemia or intoxication with lithium, bromide, or iodide. Elevated values most commonly indicate metabolic acidosis but can reflect laboratory error, metabolic alkalosis, hyperphosphatemia, or paraproteinemia. Metabolic acidosis can be divided into high anion and normal anion gap varieties, which can be present alone or concurrently. A presumed 1:1 stoichiometry between change in the serum anion gap (⌬AG) and change in the serum bicarbonate concentration (⌬HCO 3 ؊ ) has been used to uncover the concurrence of mixed metabolic acid-base disorders in patients with high anion gap acidosis. However, recent studies indicate variability in the ⌬AG/⌬HCO 3 ؊ in this disorder. This observation undercuts the ability to use this ratio alone to detect complex acid-base disorders, thus emphasizing the need to consider additional information to obtain the appropriate diagnosis. Despite these caveats, calculation of the serum anion gap remains an inexpensive and effective tool that aids detection of various acid-base disorders, hematologic malignancies, and intoxications.

Drug-induced acid-base disorders

“…Calculating the serum anion gap (AG) is the first step to differentiate between ABDs [1][2][3][4][5]. The AG must be corrected for serum albumin levels, and it must be considered that several factors (e.g., paraproteinemia, lithium, and bromide intoxication; hypercalcemia; hypermagnesemia; syndrome of inappropriate antidiuretic hormone secretion (SIADH); severe hyperphosphatemia), as well as the laboratory measurement method used [1], could interfere with the calculation. Clinical information, including medical history and laboratory data, must be obtained from the patient, especially in differentiating possible mixed acid-base disturbances.…”

“…The AG can be calculated using the simplified formula [ [1,[6][7][8][9]. It is noteworthy that the AG depends on plasma albumin levels, and hypoalbuminemia is a common finding in hospitalized patients.…”

Clinical and laboratory approaches in the diagnosis of renal tubular acidosis

“…For the reliable interpretation of plasma AG, calculated as (Na + + K + ) -(Cl − +HCO 3 − ), the range of normal values of AG should be determined for each laboratory and even for each individual compared with the baseline values, although this is difficult to accomplish in the clinical setting. The AG value represents the difference between unmeasured anions and unmeasured cations, and is affected by variations in the plasma concentrations of albumin, phosphate, calcium, and magnesium [13].…”

“…A value >100 mOsm/kg H 2 O suggests high urinary NH 4 + [18,19]. This method is valuable for bedside screening for gross changes in urinary NH 4 + concentration and is used in the diagnostic study of patients with diabetic ketoacidosis or D-lactic acidosis [13].…”

Case files of the medical toxicology fellowship at the New York City Poison Control: Bromism: Forgotten, but not gone

“…This can cause anion gaps to be low or even negative, and have been reported to reach values as low as -60 mEq/L and -97 mEq/L [25][26][27]. Bromism may not even appear in the differential diagnosis in many cases until these findings are seen on laboratory analysis [13].…”