The electrolytes in the serum must be in equilibrium. The major positively charged electrolytes (sodium, potassium) and negatively charged electrolytes (chloride and bicarbonate) are commonly measured in screening chemical tests. "Unmeasured" anions or cations make up the difference from electroneutrality.

Method 1


anion gap =

= (sodium in mEq/L) - ((chloride in mEq/L) + (HCO3 in mEq/L))


normal: 8-16 mEq/L


Method 2


anion gap =

= ((sodium in mEq/L) + (potassium in mEq/L)) - ((chloride in mEq/L) + (HCO3 in mEq/L))


normal: 10-20 mEq/L




Increases in anion gap are seen with "unmeasured" anions. In order of frequency these are:

(1) diabetic ketoacidosis

(2) uremic acidosis

(3) drug ingestion (salicylates, methanol, ethylene glycol, ethanol, penicillins)

(4) lactic acidosis

(5) decreased unmeasured cations (hypokalemia, hypocalcemia, hypomagnesemia)

(6) other (hyperalbuminemia, elevated phosphorus, administration of sulfates, laboratory error)


A decreased anion gap is less frequent

(1) decreased unmeasured anions , especially hypoalbuminemia

(2) laboratory error

(3) increased immunoglobulins (myeloma, gammopathies)

(4) increased unmeasured cations (hyperkalemia, hypercalcemia, hypermagnesemia, lithium therapy)


The anion gap can be interpreted in conjunction with the osmolal gap.


Anion Gap

Osmolal Gap




salicylate or paraldehyde



methanol or ethylene glycol


The serum anion gap is affected by the chemical analyzer used, so that the normal range needs to be determined for each institution.

• Some chemical analyzers have a lower normal range that overlaps with that seen with other analyzers.

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