From the Guidelines
An elevated Anion Gap (AG) is a laboratory finding that occurs when the difference between measured positively charged ions (cations) and negatively charged ions (anions) in the blood exceeds the normal range of 8-12 mEq/L, typically indicating the presence of excess acid in the bloodstream.
Definition and Calculation
The anion gap is calculated as (Na+) - (Cl + HCO3) (mEq/l) 1. This gap represents unmeasured anions in the blood, primarily consisting of proteins, phosphates, sulfates, and organic acids.
Causes and Clinical Significance
The most common causes of an elevated anion gap are grouped under the mnemonic MUDPILES: Methanol, Uremia (kidney failure), Diabetic ketoacidosis, Propylene glycol, Isoniazid or Iron, Lactic acidosis, Ethylene glycol, and Salicylates (aspirin) 1. The elevation occurs because these conditions produce acids that contribute to the unmeasured anion pool. For example, in diabetic ketoacidosis, ketone bodies accumulate; in lactic acidosis, lactic acid builds up; and in kidney failure, various organic acids cannot be cleared.
Recent Guidelines and Recommendations
According to recent guidelines, an anion gap > 27 mmol/L is a strong recommendation for extracorporeal treatment in patients with ethylene glycol poisoning 1. Identifying an elevated anion gap helps clinicians narrow down potential diagnoses and guides appropriate treatment for the underlying condition causing the acid-base disturbance.
Key Points to Consider
- The anion gap is a critical laboratory finding that can indicate the presence of excess acid in the bloodstream.
- The most common causes of an elevated anion gap are grouped under the mnemonic MUDPILES.
- Recent guidelines recommend extracorporeal treatment for patients with ethylene glycol poisoning and an anion gap > 27 mmol/L.
- Identifying an elevated anion gap is essential for guiding appropriate treatment and improving patient outcomes. Some studies suggest that the anion gap can be falsely elevated by certain factors, such as glycolate concentration 1. However, the most recent and highest-quality study recommends using the anion gap as a guide for extracorporeal treatment in patients with ethylene glycol poisoning 1.
From the Research
Definition of Elevated Anion Gap
An elevated Anion Gap (AG) is a condition where the difference between the sodium concentration and the sum of chloride and bicarbonate concentrations in the blood is higher than normal 2, 3, 4. The anion gap is calculated using the formula: Anion Gap = Na - (Cl + HCO3).
Causes of Elevated Anion Gap
The causes of an elevated anion gap can be divided into several categories, including:
- Lactate accumulation, which can occur due to decreased oxygen delivery or defective oxygen utilization 3, 5
- Ketoacid production, which is usually secondary to diabetes or alcohol 3
- Toxin or drug ingestion, such as methanol, ethylene glycol, or salicylates 2, 3
- Uremia, which is associated with a mild acidosis secondary to decreased ammonia secretion and an anion gap caused by the retention of unmeasured anions 3
Calculation and Interpretation of Anion Gap
The anion gap can be calculated using the formula: Anion Gap = Na - (Cl + HCO3) 4. The normal value of the anion gap can vary depending on the laboratory, but it is typically around 8-12 mEq/L 6. An elevated anion gap can indicate the presence of an acid-base disorder, and the ratio of Δ anion gap to Δ bicarbonate (ΔAG/ΔHCO3) can be used to detect coexisting acid-base disorders 5.
Limitations of Anion Gap Calculation
There are several limitations to the calculation of the anion gap, including the wide range of normal values and the effect of perturbations other than changes in acid-base balance 6. Additionally, the type of retained anion can affect the magnitude of the increase in anion gap relative to the change in serum bicarbonate 6.