From the Guidelines
High anion gap metabolic acidosis is primarily caused by conditions such as diabetic ketoacidosis, lactic acidosis, kidney failure, and ingestion of certain toxins like methanol, ethylene glycol, and salicylates, as well as metformin and alcoholic ketoacidosis. These conditions lead to an accumulation of excess acid in the bloodstream, which the body attempts to compensate for by increasing the respiratory rate to eliminate carbon dioxide. The anion gap increases due to the addition of unmeasured anions to the blood, disrupting the normal electrolyte balance.
Common Causes
- Diabetic ketoacidosis, characterized by insulin deficiency leading to ketone production 1
- Lactic acidosis, resulting from tissue hypoxia in conditions like sepsis or cardiac arrest
- Kidney failure, which impairs acid excretion, although it more typically presents as hyperchloremic acidosis 1
- Certain toxins and medications, including methanol, ethylene glycol, salicylates, metformin, and paraldehyde 1
- Alcoholic ketoacidosis, distinguished by clinical history and plasma glucose concentrations that range from mildly elevated to hypoglycemia 1
Diagnosis and Treatment
Diagnosis involves distinguishing between these causes, with tools such as measurement of blood lactate, serum salicylate, and blood methanol levels being helpful 1. Treatment focuses on addressing the underlying cause, such as administering insulin for diabetic ketoacidosis, dialysis for severe kidney failure or toxin ingestion, and supportive care with intravenous fluids. In severe cases, sodium bicarbonate may be considered to help correct the acidosis, particularly in cases with a pH below 7.1.
Clinical Considerations
Clinical history and laboratory findings, such as the presence of calcium oxalate and hippurate crystals in the urine suggesting ethylene glycol ingestion, or the characteristic strong odor on the breath indicating paraldehyde ingestion, are crucial for diagnosis 1. The presence of an osmolar gap in addition to the anion gap acidosis can also indicate intoxication with low-molecular-weight organic compounds.
From the Research
Causes of High Anion Gap Metabolic Acidosis
- Lactic acidosis, which can be caused by decreased oxygen delivery or defective oxygen utilization 2
- Ketoacidosis, usually secondary to diabetes or alcohol 2, 3, 4, 5
- Toxin or drug-induced acidosis, such as methanol, ethylene glycol, and salicylates 2, 4
- Uremia, associated with a mild acidosis secondary to decreased ammonia secretion and an anion gap caused by the retention of unmeasured anions 2
- 5-oxoproline (pyroglutamic acid) intoxication, which can be caused by paracetamol intake, especially in patients with female gender, sepsis, impaired renal function, or uncontrolled type 2 diabetes mellitus 3, 4
- Severe increases in concentration of phosphorus, causing hyperphosphatemic acidosis 5
- Benzoic acid, a weak acid that can contribute to anion gap metabolic acidosis, especially in patients taking sodium benzoate powder as a dietary supplement 6
- Acute renal failure, which can cause an accumulation of anions and lead to high anion gap metabolic acidosis 3, 4, 5
- Sepsis, which can cause lactic acidosis and other forms of high anion gap metabolic acidosis 3
- Hyperglycemia, which can cause ketoacidosis and other forms of high anion gap metabolic acidosis 3
- Prior gastric bypass surgery, which can cause D-lactate accumulation and high anion gap metabolic acidosis 3