Serum Anion Gap: Its Uses and Limitations in Clinical Medicine

Medical and Research Services VHAGLA Healthcare System, UCLA Membrane Biology Laboratory, and Division of Nephrology VHAGLA Healthcare System and David Geffen School of Medicine, Los Angeles, California 90073, USA.
Clinical Journal of the American Society of Nephrology (Impact Factor: 4.61). 02/2007; 2(1):162-74. DOI: 10.2215/CJN.03020906
Source: PubMed


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 (DeltaAG) and change in the serum bicarbonate concentration (DeltaHCO(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 DeltaAG/DeltaHCO(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.

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    • "Rarely, metabolic acidosis can be masked by concomitant metabolic alkalosis from exposure to a high bicarbonate dialysate during hemodialysis. Mixed acid base disorder in this case can produce normal or minimally reduced serum bicarbonate; nevertheless, a high anion gap will be present in DKA and serves as a clue for DKA.29 Additionally, anion gap in ESKD patients can be elevated in the absence of DKA because of accumulation of organic acids and reduced acid secretion from kidney failure.30 "
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    ABSTRACT: Diabetic ketoacidosis (DKA) is a rare yet potentially fatal hyperglycemic crisis that can occur in patients with both type 1 and 2 diabetes mellitus. Due to its increasing incidence and economic impact related to the treatment and associated morbidity, effective management and prevention is key. Elements of management include making the appropriate diagnosis using current laboratory tools and clinical criteria and coordinating fluid resuscitation, insulin therapy, and electrolyte replacement through feedback obtained from timely patient monitoring and knowledge of resolution criteria. In addition, awareness of special populations such as patients with renal disease presenting with DKA is important. During the DKA therapy, complications may arise and appropriate strategies to prevent these complications are required. DKA prevention strategies including patient and provider education are important. This review aims to provide a brief overview of DKA from its pathophysiology to clinical presentation with in depth focus on up-to-date therapeutic management.
    Full-text · Article · Jun 2014 · Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
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    • "An alternative collective term for unmeasured ions is that of strong ion gap (SIG). Thus, in the absence of significant increases in the concentrations of the unmeasured ions, the AG is formed mainly by the negative charges contributed by the nonvolatile weak acids, mostly albumin and to a lesser extend phosphate [1] [2]. "
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    ABSTRACT: Purpose: To determine the effect of each of independent acid base variables on the anion gap (AG) value in cardiac surgical patients. Methods: This retrospective study involved 128 cardiac surgical patients admitted for postoperative care. The variation of AG (AGvar) between the day of admission and the first postoperative day was correlated via a multiple linear regression model with the respective variations of the independent acid base variables, that is, apparent strong ion difference (SIDa), strong ion gap (SIG), carbon dioxide (PCO2), and albumin and phosphate concentrations. Results: The variations of all the above variables contributed significantly to the prediction of AGvar (adjusted R (2) = 0.9999, F = 201890.24, and P < 0.001). According to the standardized coefficients (β), SIGvar (β = 0.948, P < 0.001), [Albumin]var (β = 0.260, P < 0.001), and [Phosphate]var (β = 0.191, P < 0.001) were the major determinants of AGvar with lesser contributions from SIDa, var (β = 0.071, P < 0.001) and PCO2, var (β = -0.067, P < 0.001). Conclusions: All the independent acid base variables contribute to the prediction of the AG value. However, albumin and phosphate and SIG variations seem to be the most important predictors, while AG appears to be rather stable with changes in PCO2 and SIDa.
    Full-text · Article · Feb 2014 · The Scientific World Journal
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    • "The anion gap (AG) represents the difference between the measured anion and cation concentrations in the serum, and is used by clinicians to diagnose acid base problems, especially in unsuspected cases of acidosis, alkalosis, drug poisoning, and disease states, particularly in emergency rooms and intensive care units,1–5 and as a quality control measure by laboratories. Although the concept of AG arose from the gamblegram described in 1939, it did not gain widespread recognition by physicians until the 1970s after the introduction of autoanalyzers and rapid availability of measuring multiple analytes. "
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    ABSTRACT: Using flame photometry technique in the 1970s, the normal value of anion gap (AG) was determined to be 12 ± 4 meq/L. However, with introduction of the autoanalyzers using an ion-selective electrode (ISE), the anion gap value has fallen to lower levels. A retrospective study of US veterans from a single medical center was performed to determine the value of the anion gap in subjects with normal renal function and normal serum albumin and in patients with lactic acidosis and end-stage renal disease on dialysis. In 409 patients with an estimated glomerular filtration rate ≥60 mL/min/1.73 m(2) body surface area and serum albumin ≥4 g/dL, the mean AG was 7.2 ± 2 (range 3-11) meq/L. In 299 patients with lactic acidosis (lactate level ≥4 meq/L) and 68 patients with endstage renal disease on dialysis, the mean AG was 12.5 meq/L and 12.4 meq/L, respectively. A value <2 meq/L should be considered a low anion gap and a possible clue to drug intoxication and paraproteinemic disorders. With the advent of ISE for measurement of analytes, the value of the anion gap has fallen. Physicians need to be aware of the normal AG value in their respective institutions, and laboratories need to have an established value for AG based on the type of instrument they are using.
    Full-text · Article · Jun 2013 · International Journal of Nephrology and Renovascular Disease
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