- The causes of a metabolic acidosis can be divided into those that cause an elevated anion gap and those with a normal anion gap.
- The RTAs (renal tubular acidoses). This group of disorders consists of disease states in which there is a defect in the renal excretion of acid or in the reclamation of HCO3 -. They result in a normal anion gap acidosis Proximal (type 2) RTA is due to impaired proximal tubular HCO3 - reabsorption. A proximal RTA may be isolated or can occur in association with other transport defects in Fanconi's syndrome. Causes include inherited disorders (cystinosis, galactosemia, Wilson's disease), toxins (heavy metals, outdated tetracycline, ifosfamide), multiple myeloma, autoimmune diseases (Sj-gren's syndrome), amyloidosis, and acetazolamide use. Osteomalacia or osteopenia is commonly associated with type 2 RTA due to the associated phosphaturia and calcitriol deficiency (calcitriol is made by the normal proximal tubule, which is dysfunctional in this disorder).
- Distal (type 1) RTA results from impaired distal H+ secretion (urine pH >5.5). Several unique mechanisms characteristic of various disease states can result in the low distal H+ secretion seen:
- Low H+/adenosine triphosphatase pump activity may be associated with inherited disorders (Ehlers-Danlos, Wilson's disease), autoimmune disease (Sj-gren's syndrome, lupus, rheumatoid arthritis, or any form of chronic active hepatitis), medullary interstitial disease (medullar sponge kidney or nephrocalcinosis, light chain nephropathy), or drugs and toxins
- (lithium, toluene).
- Back-leak of H+ due to increased membrane permeability (e.g., amphotericin B) Impairment in distal Na+ reabsorption resulting in reduced voltage augmentation of H+ secretion. This can be seen with marked volume 67depletion, urinary tract obstruction, sickle cell nephropathy, and amiloride or triamterene use.
- Hypoaldosteronism-associated (type 4) RTA may result from either low aldosterone levels or from resistance to its effect. The result is a decline in mineralocorticoid-stimulated H+ and K+ secretion. The resulting hyperkalemia further decreases acid
- excretion through an inhibition of NH4 + recycling in the nephron.
- Hyporeninemic hypoaldosteronism can be found with diabetes and certain drugs (NSAIDs, beta-blockers, cyclosporine). Hyperreninemic hypoaldosteronism is seen with ACE inhibitor/angiotensin receptor blocker use, heparin, ketoconazole, and Addison's disease. Aldosterone resistance can be seen with spironolactone use.
- RTA of renal insufficiency occurs when the GFR falls to 15â??30 mL/min and there is insufficient renal mass to produce enough NH4 to excrete the daily acid load.