From the Guidelines
A low anion gap is primarily caused by hypoalbuminemia, which is the most common cause in clinical practice, as it reduces the measured anion gap due to decreased negative charges from albumin 1.
Causes of Low Anion Gap
The anion gap is calculated as Na+ + K+ - HCO3− - Cl−, and various factors can influence this calculation.
- Hypoalbuminemia is a major cause, as albumin carries negative charges, and its decrease reduces the measured anion gap.
- Other causes include:
- Paraproteinemias, such as multiple myeloma, where abnormal immunoglobulins with positive charges neutralize negative charges in the blood.
- Laboratory error, particularly when values are extremely low.
- Lithium toxicity, as lithium is a cation not routinely measured in the anion gap calculation.
- Severe hypermagnesemia, hypercalcemia, and hypernatremia, which can contribute to a low anion gap by increasing unmeasured cations.
- Bromide intoxication, though rare, can artificially lower the anion gap due to laboratory interference.
- Polymyxin B therapy has also been associated with a low anion gap.
Clinical Approach
When encountering a low anion gap, clinicians should first check albumin levels and consider ordering protein electrophoresis if paraproteinemia is suspected, especially in elderly patients with unexplained low anion gap.
- It is essential to rule out laboratory errors and consider the clinical context, including the patient's medical history and current medications.
- The study by 1 provides insight into the complexities of anion gap calculations and the importance of considering multiple factors when interpreting electrolyte imbalances.
Key Considerations
- The anion gap calculation can be influenced by various factors, including the presence of unmeasured cations or anions.
- Clinicians should be aware of the potential causes of a low anion gap and take a systematic approach to evaluating patients with this finding.
- Further research, such as the study by 1, can provide valuable insights into the management of patients with electrolyte imbalances and help guide clinical decision-making.
From the Research
Causes of Low Anion Gap
The causes of a low anion gap are not extensively discussed in the provided studies, as they primarily focus on high anion gap metabolic acidosis or the concept of anion gap in general. However, we can infer some information from the studies:
- A low anion gap is defined as an anion gap value of < 3 mEq/L, according to 2.
- The clinical significance of a low anion gap is often unrecognized, but it can be a useful diagnostic tool for life-threatening intoxications or occult neoplasms, such as multiple myeloma 2.
- A low anion gap may mask the identification of a high gap metabolic acidosis in certain patients 2.
- The constituents of the anion gap and a differential diagnosis for a low anion gap can be built using case examples, as discussed in 3.
- The serum anion gap is calculated as [Na+] - ([Cl-] + [HCO3-]) = Unmeasured anions - Unmeasured cations, and the normal gap is mostly due to negatively charged albumin 4.
Possible Causes
Some possible causes of a low anion gap can be inferred from the studies, including:
- Laboratory error or variation in measurement techniques
- Certain medical conditions that affect albumin levels or other unmeasured anions
- The presence of certain ions or substances that can affect the calculation of the anion gap However, these causes are not explicitly discussed in the provided studies, and further research would be needed to determine the specific causes of a low anion gap. The studies primarily focus on high anion gap metabolic acidosis, and the discussion of low anion gap is limited to its definition, clinical significance, and calculation 2, 3, 4, 5.