Overview
This lecture reviews the differential diagnosis, mechanisms, key features, and approach to diagnosing normal anion gap (hyperchloremic) metabolic acidosis, with emphasis on renal tubular acidosis (RTA), diarrhea, renal failure, and excess saline infusion.
Causes of Normal Anion Gap Metabolic Acidosis
- Normal anion gap metabolic acidosis is caused by either a gain of hydrogen ions or a loss of bicarbonate.
- Main etiologies include GI losses (diarrhea), renal tubular acidosis (RTA), renal failure, and excessive normal saline infusion.
- Less common causes: hyperalimentation (TPN/feeding), cholestyramine use, oral calcium chloride, and urinary diversions.
- Common, clinically relevant causes: diarrhea, renal failure, type 4 RTA, normal saline infusion.
Renal Tubular Acidosis (RTA)
- RTA involves a defect in kidney acid-base regulation without overt renal failure.
- Type 1 (Distal) RTA: defect in collecting duct hydrogen excretion; causes include autoimmune disease, drugs, hypercalciuria.
- Type 2 (Proximal) RTA: defect in proximal tubular bicarbonate reabsorption; can be isolated or part of Fanconi syndrome.
- Type 4 RTA: usually due to aldosterone deficiency or resistance; often caused by ACE inhibitors, ARBs, NSAIDs, diabetes, or certain medications.
Clinical and Laboratory Features of RTAs
- Type 1 RTA: low serum bicarb, normal/low K+, high urine pH, high urine anion gap.
- Type 2 RTA: low/normal K+, variable urine pH, high fractional excretion of bicarbonate.
- Type 4 RTA: high K+, low urine pH, high urine anion gap.
- Type 3 RTA is rare and not clinically significant in most contexts.
Other Causes and Mechanisms
- Diarrhea and other GI losses lead to loss of bicarbonate-rich fluids, causing acidosis.
- Renal failure impairs ammonium excretion, leading to acidosis, sometimes with elevated anion gap.
- Urinary diversions (e.g., ureterosigmoidostomy) cause acidosis by loss of bicarbonate and reabsorption of ammonium.
- Hyperkalemia can cause acidosis via potassium-hydrogen exchange and impaired distal hydrogen secretion.
- Infusion of normal saline may cause mild acidosis that resolves when stopped.
Diagnostic Approach
- Stop normal saline infusion as first step if present.
- If creatinine clearance <40 mL/min, suspect renal failure.
- Assess serum potassium, urine pH, and urine anion gap to differentiate GI causes, types of RTA, and renal failure.
- Negative or low urine anion gap suggests increased ammonium excretion (usually GI loss); positive urine anion gap suggests impaired renal acid excretion (RTA or renal failure).
Key Terms & Definitions
- Normal Anion Gap Metabolic Acidosis — Acidosis with no increase in unmeasured anions; mainly due to bicarbonate loss or hydrogen gain.
- Renal Tubular Acidosis (RTA) — Defect in kidney acid-base regulation, classified as type 1 (distal), type 2 (proximal), or type 4 (hypoaldosteronism).
- Urine Anion Gap (UAG) — Calculation: (urine Na+ + K+) – Cl–; indirect measure of urine ammonium excretion.
- Fanconi Syndrome — Proximal tubule disorder with loss of multiple solutes, including bicarbonate.
- Hyperalimentation — Excessive parenteral or enteral feeding leading to acidosis.
- Ureterosigmoidostomy — Urinary diversion that can cause bicarbonate loss and acidosis.
Action Items / Next Steps
- Review lecture 10 on metabolic alkalosis.
- Memorize the stepwise diagnostic approach using potassium, urine pH, and urine anion gap.
- Be able to differentiate the lab findings among the types of RTA.