What are the causes of non-anion gap acidosis?

From the Guidelines

Non-anion gap acidosis is primarily caused by the use of excessive saline for fluid and electrolyte replacement, leading to hyperchloremia as chloride from intravenous fluids replaces ketoanions lost as sodium and potassium salts during osmotic diuresis, as seen in patients recovering from diabetic ketoacidosis (DKA) 1. The causes of non-anion gap acidosis can be broken down into several key categories, including:

• Gastrointestinal bicarbonate loss, such as diarrhea, pancreatic or biliary fistulas, and ureterosigmoidostomy
• Renal tubular acidosis, including types 1,2, and 4, which involve defects in acid secretion or bicarbonate reabsorption
• Medication effects, such as carbonic anhydrase inhibitors like acetazolamide and spironolactone
• Excessive administration of chloride-containing solutions, like normal saline, which can lead to dilutional acidosis However, in the context of recent and high-quality evidence, the use of excessive saline for fluid and electrolyte replacement is a significant cause of non-anion gap acidosis, particularly in patients recovering from DKA 1. Some key points to consider when evaluating non-anion gap acidosis include:
• The role of hyperchloremia in the development of non-anion gap acidosis
• The importance of identifying and addressing underlying causes, such as gastrointestinal bicarbonate loss or renal tubular acidosis
• The potential for certain medications to contribute to the development of non-anion gap acidosis
• The need to carefully manage fluid and electrolyte replacement to avoid exacerbating non-anion gap acidosis, particularly in patients with acute renal failure or extreme oliguria 1.

From the Research

Causes of Non-Anion Gap Acidosis

• 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 4
• Renal tubular acidosis (RTA) due to various underlying etiologies that impair the kidney's ability to retain bicarbonate or excrete acid 5
• Ibuprofen use, which can cause distal RTA and hypokalemia 5
• Chronic renal failure, which can initially cause a non-anion gap acidosis secondary to the loss of bicarbonate from the proximal tubule and impaired excretion in the distal tubule 6

Mechanisms

• Impaired excretion of organic and inorganic acids in the distal tubule 6
• Loss of bicarbonate from the proximal tubule 6
• Increased chronic acid load and bicarbonate deficit 4
• Hypokalemia, which can contribute to the development of non-anion gap metabolic acidosis 4, 5