From the Guidelines
Non-anion gap metabolic acidosis is primarily caused by bicarbonate loss or hydrogen ion retention, with the main causes including gastrointestinal bicarbonate loss, renal tubular acidosis, and medication-induced acidosis. The causes of non-anion gap metabolic acidosis can be broken down into several key categories, including:
- Gastrointestinal bicarbonate loss through diarrhea or intestinal fistulas, which directly removes alkaline secretions from the body 1
- Renal tubular acidosis (RTA), with Type 1 (distal) RTA resulting from impaired hydrogen ion secretion in the distal tubule, Type 2 (proximal) RTA causing bicarbonate wasting due to decreased reabsorption, and Type 4 RTA occurring from aldosterone deficiency or resistance
- Medication-induced acidosis, particularly from carbonic anhydrase inhibitors like acetazolamide, which increase bicarbonate excretion, as well as other medications such as topiramate, certain antibiotics, and immunosuppressants like cyclosporine
- Dilutional acidosis, which can occur with rapid infusion of non-bicarbonate containing fluids, especially normal saline (0.9% NaCl), leading to hyperchloremic acidosis
- Recovery from ketoacidosis, which may temporarily present as non-anion gap acidosis as ketones are cleared faster than bicarbonate is regenerated
- Urinary diversions using intestinal segments, which can cause acidosis due to chloride reabsorption and bicarbonate secretion by intestinal mucosa It's also important to note that a Western diet low in fruits and vegetables and high in animal protein can lead to an imbalance between nonvolatile acids and available alkali, resulting in a chronic low-grade metabolic acidosis that worsens with age as kidney function declines 1. Recognizing these causes is essential for appropriate management, which typically involves addressing the underlying condition and sometimes providing bicarbonate supplementation.
From the Research
Causes of Non-Anion Gap Metabolic Acidosis
The causes of non-anion gap metabolic acidosis can be attributed to several factors, including:
- Loss of large quantities of base secondary to diarrhea 2
- Administration of large quantities of chloride-containing solutions in the treatment of hypovolemia and various shock states 2
- High-volume ileostomy output causing large bicarbonate losses 3
- Ileal neobladder urinary diversion for the treatment of bladder cancer, which can lead to a urinary tract infection and ureteroenterostomy 4
- Bicarbonate loss via the gastrointestinal tract or the urine 5
- Urine acidification defects, which can be caused by intrinsic defects in the hydrogen ion pump, failure to augment hydrogen ion secretion, or failure to generate a favorable chemical gradient 5
Clinical Presentation and Evaluation
Non-anion gap metabolic acidosis can present as a form of either acute or chronic metabolic acidosis 3. A complete clinical history and physical examination are critical initial steps to begin the evaluation process, followed by measuring serum electrolytes with a focus on potassium level, blood gas, urine pH, and either direct or indirect urine ammonium concentration 3.
Underlying Mechanisms
The underlying mechanisms of non-anion gap metabolic acidosis include loss of base, increased acid load, and impaired renal acidification 2, 5. These mechanisms can lead to a decrease in serum bicarbonate concentration and a compensatory increase in chloride concentration, resulting in a non-anion gap metabolic acidosis 2.