From the Guidelines
The anion gap is a critical diagnostic tool that signifies the presence of unmeasured anions in the serum, helping to identify and manage various acid-base disorders, particularly high-anion gap metabolic acidosis, as seen in conditions like diabetic ketoacidosis, lactic acidosis, and certain poisonings, such as ethylene glycol poisoning 1.
Calculation and Interpretation
The anion gap is calculated using the formula: Anion Gap = [Na+] - ([Cl-] + [HCO3-]), which works because electrical neutrality must be maintained in the body, so any unmeasured anions will be reflected in the gap between measured positive and negative ions.
- A normal anion gap typically ranges from 8 to 12 mEq/L, though reference ranges may vary slightly between laboratories.
- An elevated anion gap often indicates metabolic acidosis caused by increased acid production or decreased acid excretion.
Clinical Applications
The anion gap is particularly useful in diagnosing and managing conditions like diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar syndrome (HHS), where it can help distinguish between different types of metabolic acidosis 1.
- In the context of ethylene glycol poisoning, an anion gap of 24–28 mmol/L and > 28 mmol/L can be used as surrogate markers for glycolate concentration and correlate with clinical outcomes, guiding the need for extracorporeal treatment 1.
Limitations and Considerations
It is essential to consider other acid-base parameters, such as pH, HCO3–, and base excess, when interpreting the anion gap, especially in cases where the anion gap may overestimate or underestimate the glycolate concentration due to concomitant conditions like acute kidney injury or ketoacidosis 1.
From the Research
Anion Gap Significance
The anion gap is a useful tool in evaluating patients with acid-base disorders, as it helps in identifying the type of metabolic acidosis and its underlying cause 2, 3.
- The anion gap measurement can distinguish between high anion gap acidosis and normal anion gap acidosis, which is essential for differential diagnosis 2.
- A high anion gap acidosis can be caused by various factors, including lactic acidosis, ketoacidosis, toxin or drug ingestion, and uremia 3.
- The delta gap and delta ratio can provide further information about the type of acid-base disorder, with a delta ratio of 1:1 indicating an uncomplicated high anion gap acidosis, and values below or above 1:1 suggesting combined acid-base disorders 2.
- The urine anion gap can also be used to estimate urine ammonium excretion and help diagnose certain types of metabolic acidosis, such as normal anion gap acidosis secondary to diarrhea 2.
Clinical Utility
The anion gap has several clinical applications, including:
- Identifying errors in electrolyte measurement 4
- Detecting paraproteins 4
- Evaluating patients with suspected acid-base disorders 4
- Distinguishing between different types of metabolic acidosis, such as lactic acidosis and ketoacidosis 5, 6
Limitations
The anion gap also has some limitations, including:
- A wide range of normal values, which can make it difficult to detect increases in anion concentration 4
- The type of retained anion can affect the magnitude of the increase in anion gap relative to changes in serum bicarbonate 4
- The anion gap may not be effective in identifying mild acid-base disturbances 4