Answering your questions; normal range for anion gap.

Q What is the normal range for anion gap with the formula Na-(Cl+CO2)? With the formula (Na+K)- (Cl+CO2)? Which one should be used?

A The anion gap is defined as the difference between the major measured cation, sodium, and the major measured anions, chloride, and bicarbonate. The anion gap is usually calculated as [N[a.sup.+]-(C[l.sup.-] + HC[O.sub.3.sup.-])]. Other cations present in blood but not normally included in the anion gap calculation include potassium, calcium, magnesium, and IgG. Likewise, there are a number of anions present in blood that are not included in the calculation. These include sulfate, phosphate, and most plasma proteins. In plasma, there is an exact balance of positively charged cations and negatively charged anions. The total amount of each is approximately 150 to 155 mmol/L.

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The anion gap is commonly used in clinical practice, especially in critically ill patients, as an approximation of the difference between the concentration of unmeasured anions and unmeasured cations in plasma. Normal values for the anion gap can differ markedly between instruments, primarily due to differences in measurement of sodium and chloride. One recent study found that mean anion gaps for healthy subjects, measured on different instruments, ranged from approximately 6 mmol/L to 12 mmol/L. (1) These data show that the mean measured anion gap assessed by different analyzers can vary significantly. Thus, each laboratory should establish an anion gap that is appropriate to the instrument being used to calculate this parameter. The often-cited reference range for the anion gap of 8 mmol/L to 16 mmol/L, since lowered to 3 mmol/L to 11 mmol/L following the implementation of ion-selective electrodes for measuring electrolytes, should be used only as a rough guideline. (2)

Most laboratories do not use potassium in the calculation of the anion gap. Potassium is a major intracellular cation and is usually present in serum in a relatively narrow range of approximately 3.5 mmol/L to 5.0 mmol/L. Potassium is not included in the anion gap formula since its variation in the serum is relatively small, and its contribution to changes in the anion gap is relatively insignificant.

An increase in the anion gap represents a change in the pattern of anions and cations in serum. (3) An increased anion gap may be due to decreases in calcium, magnesium, or immunoglobulins. More commonly however, increased anion gaps are due to replacement of bicarbonate with the anion of an organic acid.

--Violetta Kolesnikova, MD

Department of Pathology

Oregon Health and Science University

Portland, OR

Edited by Daniel M. Baer, MD

Daniel M. Baer, MD, is professor emeritus of laboratory medicine at Oregon Health and Science University in Portland, OR, and a member of MLO's editorial advisory board.

Table 1. Examples of disorders causing an increased anion gap.

Ketone bodies                    In diabetic ketoacidosis, alcoholism,
                                 starvation

Lactic acid                      In circulatory or respiratory failure,
                                 sepsis, ischemic bowel or limb,
                                 seizures, malignancy, hepatic failure,
                                 CO poisoning, or cyanide poisoning

Formic acid                      In methanol poisoning

Oxalic acid                      In ethylene glycol poisoning

Salicylic acid                   In aspirin poisoning

Accumulation of organic anions   In renal failure
such as phosphates and sulfates

Table 2. Examples of disorders causing a low or negative anion gap.

Increase in unmeasured     Ca, Mg, Li
cations

Decrease in total protein  Especially
                           albumin

Artifact                   Bromide
                           ingestion

Multiple myeloma in young  Rare
patients

References

(1.) Paulson WD, Roberts WL, Lurie AA, Koch DD, Butch AW, Aguanno JJ. Wide variation in serum anion gap measurements by chemistry analyzers. Amer J Clin Pathol. 1998;110(6):735-742.

(2.) Lolekha PH. Update on value of the anion gap in clinical diagnosis and laboratory evaluation. Clin Chim Acta. 2001;307(1-2):33-36.

(3.) Henry JB. Clinical Diagnosis and Management by Laboratory Methods. 20th ed. New York, NY: WB Saunders Co.; 2001.