Anion gap

Background

A normal gap is 12 +/- 4 (i.e. 8 to 16). The anion gap is the difference between measured cations and measured anions in serum. This difference does not reflect a true disparity between positive and negative charges, given that serum actually is electrically neutral when all serum cations and anions are measured. Rather, the anion gap is a measurement artifact resulting from the fact that only certain cations and anions are routinely measured. Anion gap metabolic acidosis is secondary to the addition of endogenous or exogenous acid

• AG = Na - (Cl + HCO3)
• Normal Anion Gap = 12+/-4 (8-16)
• 12-20 mEq/L when including K+

Cutoffs for "normal" Anion Gap are laboratory and equipment specific. Newer technology and equipment have been shown to measure "low" AG in otherwise normal, healthy people.

Elevated Anion Gap

Differential Diagnosis

MUDPILES

• M - Methanol, metformin
• U - Uremia
• D - DKA
• P - Paraldehyde, phenformin
• I - Iron, INH, ibuprofen (large ingestions)
• L - Lactic acidosis
• E - Ethylene glycol
• S - Salicylates

Also:

• Starvation/ETOH ketoacidosis
• Carbon Monoxide (CO), CN poisoning (increased lactate), colchicine
• Toluene
• Chronic acetaminophen use

KILR

• K – Ketoacidosis - (diabetic, Alcohol, Starvation)
• I – Ingestion - (Salicylates, Acetaminophen, Methanol, Ethylene glycol, CO, CN, Iron, INH)
• L – Lactic acidosis - (infection, hemorrhage, hypoperfusion, Alcohol, Metformin)
• R – Renal - (Uremia)

Low Anion Gap

Differential Diagnosis

• Lab error
• Decreased "unmeasured" anions
  • Hypoalbuminemia
• Increased "unmeasured" cations
  • Hyperkalemia
  • Hypercalcemia
  • Hypermagnesemia
  • Lithium Toxicity
• Increased cationic paraprotein
• Multiple myeloma
  • Polyclonal IgG gammopathy
• Pseudo
  • Severe Hypernatremia (>170 meq/L)
    • True conc of Na is underestimated
  • Marked hyperlipidemia
    • Leads to overestimation of plasma Cl conc)
  • Bromide toxicity (e.g. for myasthenia gravis and some herbal medications)
    • Assay mistakenly reads Br as Cl
    • May have negative anion gap
  • Elevated serum iodide

• AG falls by 2.5 meq/L for every 1 g/dL reduction in albumin concentration

See Also

• Anion Gap and Osmolar Gap (High)
• Anion Gap (High)
• Osmolal or Osmolar Gap
• Toxidromes
• Acidosis

Calculators

Anion Gap

Anion Gap Calculator

Parameter	Value
Sodium (Na⁺) mEq/L
Chloride (Cl⁻) mEq/L
Bicarbonate (HCO₃⁻) mEq/L
Albumin (g/dL) — optional, for correction
Results
Anion Gap	mEq/L
Corrected AG (for albumin)	mEq/L
Delta-Delta Ratio (ΔAG / ΔHCO₃)

Interpretation
AG <12	Normal anion gap — Consider non-AG metabolic acidosis (HARDUPS mnemonic).
AG ≥12	Elevated anion gap — Consider MUDPILES: Methanol, Uremia, DKA, Propylene glycol, Isoniazid/Iron, Lactic acidosis, Ethylene glycol, Salicylates.
Delta-Delta Ratio
<1	Concurrent non-AG metabolic acidosis (mixed).
1–2	Pure anion gap metabolic acidosis.
>2	Concurrent metabolic alkalosis (or pre-existing elevated HCO₃).

References
Kraut JA, Madias NE. Serum anion gap: its uses and limitations in clinical medicine. Clin J Am Soc Nephrol. 2007;2:162-174. PMID 17699401. Fenves AZ et al. Increased anion gap metabolic acidosis as a result of 5-oxoproline (pyroglutamic acid). Proc (Bayl Univ Med Cent). 2006;19:364-367.

External Links

• MDCalc - Serum Osmolality/Osmolarity
• MDCalc - Anion Gap