type 2 renal tubular acidosis
Summary
Type 2 (proximal) renal tubular acidosis is caused by impaired bicarbonate reabsorption in the proximal convoluted tubule, leading to a hyperchloremic, normal anion gap metabolic acidosis with urine that can appropriately acidify (urine pH <5.5) once serum bicarbonate falls low enough. It is often associated with Fanconi syndrome and features hypokalemia due to increased distal sodium delivery and secondary hyperaldosteronism.
Detail
Pathophysiology: The proximal tubule normally reabsorbs ~85-90% of filtered bicarbonate via a Na+/H+ exchanger (NHE3) and carbonic anhydrase-dependent mechanisms. In type 2 RTA, this reabsorptive capacity is reduced, causing bicarbonaturia and a fall in serum bicarbonate until a new, lower threshold is reached at which the reduced filtered load can be reabsorbed—at this new steady state, urine pH can be appropriately acidic (<5.5) because distal acidification mechanisms remain intact. This differs from type 1 (distal) RTA, where the distal nephron cannot acidify urine below pH 5.5 regardless of systemic acidosis.
Etiology: Can be isolated or part of generalized proximal tubular dysfunction (Fanconi syndrome), which also causes glucosuria, phosphaturia, aminoaciduria, and uricosuria. Causes include multiple myeloma (light chain nephropathy), Wilson disease, cystinosis, heavy metal toxicity (lead, cadmium), carbonic anhydrase inhibitors (acetazolamide), ifosfamide, and tenofovir. Also seen in vitamin D deficiency and secondary hyperparathyroidism.
Clinical features: Hyperchloremic normal anion gap metabolic acidosis, hypokalemia (from enhanced distal Na-K exchange due to increased distal Na delivery and secondary hyperaldosteronism), growth failure/rickets in children (due to bicarbonate wasting and phosphate wasting), and increased risk of nephrocalcinosis is LESS common than in type 1 RTA (in contrast, type 1 RTA has higher risk of nephrocalcinosis/nephrolithiasis due to alkaline urine and hypocitraturia).
Diagnosis: Fractional excretion of bicarbonate >15% after bicarbonate loading; urine anion gap is negative (indicating appropriate ammonium excretion, distinguishing from type 1 RTA). Look for other features of Fanconi syndrome.
Treatment: Large doses of oral bicarbonate or citrate (higher doses than type 1 RTA due to ongoing bicarbonate wasting), potassium supplementation, treatment of underlying cause. Thiazide diuretics can help by causing mild volume depletion, enhancing proximal bicarbonate reabsorption.
High-yield comparison: Type 1 RTA (distal) - inability to acidify urine, urine pH >5.5, associated with nephrocalcinosis, hypokalemia. Type 4 RTA - hyperkalemic, due to aldosterone deficiency/resistance, seen in diabetic nephropathy.
Sources
- First Aid for the USMLE Step 1
- Harrison's Principles of Internal Medicine
- UpToDate: Etiology and diagnosis of distal (type 1) and proximal (type 2) RTA
- Goldman-Cecil Medicine
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.