Decreased Serum Anion Gap

Etiology of Negative Serum Anion Gap

Artifactual Increase in Chloride/Bicarbonate Concentration: results in artifactual decrease in the anion gap
Artifactual Decrease in Sodium Concentration: results in artifactual decrease in the anion gap

Bromide Ingestion (Bromism) (see Bromide)
- Mechanism
  - Bromide Interferes with Chloride Measurement, as Bromide Ion is Interpreted as Chloride Ions (with Each Bromide Ion Being Read as Multiple Chloride Ions), Causing “Pseudohyperchloremia”
- Diagnosis: anion gap may be decreased or negative
Iodine Intoxication
- Mechanism
  - XXXX
Lithium Intoxication (see Lithium)
- Mechanism
  - Lithium Acts as an Unmeasured Cation
- Diagnosis: anion gap may be decreased or negative
Salicylate Intoxication (see Salicylates)
- Mechanism
  - Salicylate May Falsely Elevate the Serum Chloride, Due to High Salicylate Levels Altering the Permeability of Ion-Selective Electrodes Used in the Chloride Assay

Severe Hyperlipidemia (see Hyperlipidemia)
- Mechanism
  - Severe Hyperlipidemia Falsely Elevates the Chloride Concentration When Using Certain Colorimetric Assays, as Excess Lipid Affects Light Scattering
Severe Hypernatremia (see Hypernatremia)
- Mechanism
  - Occurs with Serum Na >170 mEq/L*: in this situation, the serum Na is typically underestimated

General Comments: most common etiology of decreased anion gap
Artifactual Increase in Chloride/Bicarbonate Concentration: results in artifactual decrease in the anion gap
Artifactual Decrease in Sodium Concentration: results in artifactual decrease in the anion gap

Bromide Ingestion (Bromism) (see Bromide)
- Mechanism: bromide interferes with chloride measurement (being interpreted as chloride ions, with each bromide ion being read as multiple chloride ions), causing “pseudohyperchloremia”
- Diagnosis: anion gap may be decreased or negative
Lithium Intoxication (see Lithium)
- Mechanism
  - Lithium Acts as an Unmeasured Cation
- Diagnosis: anion gap may be decreased or negative

Hypercalcemia (see Hypercalcemia)
- Mechanism
  - Due to an Increase in the Unmeasured Cation, Calcium
Hyperkalemia (see Hyperkalemia)
- Mechanism
  - Due to an Increase in the Unmeasured Cation, Potassium
Hypermagnesemia (see Hypermagnesemia)
- Mechanism
  - Due to an Increase in the Unmeasured Cation, Magnesium
  - Magnesium Sulfate Administration (see Magnesium Sulfate)
    - Increase in Serum Magnesium (Cation) is Accompanied by an Increase in Sulfate Anion -> This Will Not Change the Anion Gap
  - Magnesium Chloride Administration (see Magnesium Chloride)
    - Chloride Concentration Increases without a Change in Sodium or Bicarbonate -> This will Decrease the Anion Gap
Hypoalbuminemia (see Hypoalbuminemia)
- Epidemiology: most common etiology of decreased anion gap
- Mechanism
  - Decreased Concentration of the Unmeasured Anion, Albumin
- Clinical: anion gap decreases 2.3-2.5 mEq/L for each 1 g/dL decrease in the serum albumin -> corrected anion gap = (measured anion gap) + [2.5 x (4.5 – serum albumin)]
IgG Multiple Myeloma (see Multiple Myeloma)
- Mechanism
  - IgG Proteins are Unmeasured Cations
Polyclonal IgG Gammopathy
- Mechanism
  - IgG Proteins are Unmeasured Cations
Severe (Hyperchloremic) Non-Anion Gap Metabolic Acidosis (NAGMA) (see Metabolic Acidosis-Normal Anion Gap, [[Metabolic Acidosis-Normal Anion Gap]])
- Mechanism
  - Protons Bind to Albumin as the pH Decreases, Reducing Albumin’s Net Negative Charge

Serum anion gap: its uses and limitations in clinical medicine. Clin J Am Soc Nephrol. 2007 Jan;2(1):162-74. Epub 2006 Dec 6 [MEDLINE]
Negative anion gap and elevated osmolar gap due to lithium overdose. CMAJ. 2007 Mar 27;176(7):921-3 [MEDLINE]