From the Guidelines
An elevated anion gap without acidosis can occur due to various clinical scenarios, including laboratory error, dehydration, certain medications, and toxins, as well as early stages of conditions that typically cause anion gap metabolic acidosis. The most common causes of an elevated anion gap without acidosis include:
- Laboratory error, where measurement inaccuracies lead to falsely elevated anion gap calculations 1
- Dehydration, which can increase the anion gap by concentrating unmeasured anions without necessarily causing acidosis
- Certain medications and toxins like salicylates (aspirin) that can initially cause a mixed acid-base disorder where respiratory alkalosis compensates for metabolic acidosis, resulting in a normal pH despite an elevated anion gap
- Hyperalbuminemia, which increases the anion gap since albumin contributes negative charges
- Severe hyperphosphatemia or hypercalcemia, which can also elevate the gap without causing acidosis
- Early stages of conditions that typically cause anion gap metabolic acidosis, such as diabetic ketoacidosis, lactic acidosis, or toxic ingestions, which may present with an elevated gap before pH drops significantly
- Chronic kidney disease patients, who may have increased unmeasured anions with compensatory mechanisms maintaining normal pH
- Multiple concurrent acid-base disorders, particularly when metabolic acidosis occurs alongside metabolic alkalosis or respiratory alkalosis, can result in a normal pH despite an elevated anion gap 1. Understanding these mechanisms helps clinicians properly interpret laboratory findings and avoid missing underlying pathologies when anion gap elevation occurs without the expected acidosis. Some specific conditions, such as ethylene glycol poisoning, can also present with an elevated anion gap without acidosis, and the use of extracorporeal treatment (ECTR) may be recommended in certain cases, depending on the severity of the poisoning and the presence of other clinical indications 1. It is essential to consider the clinical context and other laboratory findings when interpreting an elevated anion gap without acidosis, as this can help guide further evaluation and management. In general, a comprehensive approach to evaluating an elevated anion gap without acidosis should include consideration of the patient's medical history, physical examination, and other laboratory findings, as well as consultation with specialists as needed.
From the Research
Causes of Anion Gap without Acidosis
- Bromide intoxication can cause a negative anion gap without acidosis, as seen in cases where patients have taken bromide-containing medications 2, 3
- Hyperchloremia with a negative anion gap can be an indicator of bromide intoxication, even in patients with preserved renal function 3
- Hypoalbuminemia can also affect the anion gap, but it is not directly related to the causes of anion gap without acidosis 4, 5
- Metabolic acidosis can cause an increased anion gap, but the question is about anion gap without acidosis, so this is not directly relevant 6
Key Points
- Bromide intoxication is a key cause of anion gap without acidosis
- Hyperchloremia with a negative anion gap can indicate bromide intoxication
- Careful history taking is essential to diagnose bromide intoxication, as some over-the-counter medications contain bromides 3