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- The causes of a metabolic acidosis can be divided into those that cause an elevated AG and those with a normal AG. Many of the causes seen in clinical practice can be found in Table 12-3.
- AG acidosis results from exposure to acids, which contribute an UA to the ECF. Common causes are DKA, lactic acidosis, and toxic alcohol ingestions.
- Non–AG acidosis can result from the loss of from the GI tract. Renal causes due to renal excretion of or disorders of renal acid handling are referred to collectively as RTAs.
- Enteric loss occurs most commonly in the setting of severe diarrhea.
- The three forms of RTA correlate with the three mechanisms that facilitate renal acid handling: proximal bicarbonate reabsorption, distal H+ secretion, and generation of NH3, the principle urinary buffer. Urinary buffers reduce the concentration of free H+ in the filtrate, thus attenuating the back leak of H+, which occurs at low urinary pH.
- Proximal (type 2) RTA is caused by impaired proximal tubular reabsorption. Causes include inherited mutations (cystinosis), heavy metals, drugs (tenofovir, ifosfamide, carbonic anhydrase inhibitors), and multiple myeloma and other monoclonal gammopathies.
- Distal (type 1) RTA results from impaired distal H+ secretion. This may occur because of impairment in H+ secretion, as seen with a variety of autoimmune (Sjögren syndrome, lupus, rheumatoid arthritis) or renal disorders. Hypercalciuria is another main cause of distal RTA in adults. It can also be caused by a back leak of H+ due to increased membrane permeability, as seen with amphotericin B.
- Distal hyperkalemic (type 4) RTA may result from either low aldosterone levels or from aldosterone resistance. The resulting hyperkalemia reduces the availability of NH3 to buffer urinary H+. Hyporeninemic hypoaldosteronism is seen with some frequency in patients with diabetes. Certain drugs, including NSAIDs, β-blockers, and cyclosporine, have also been implicated.
- Occasionally, the kidney is unable to secrete sufficient H+ because of an impaired luminal gradient. In these situations, poor filtrate delivery or impaired Na+ reabsorption in the distal nephron is responsible for decreasing the voltage gradient, which augments H+ secretion. This can be seen with marked volume depletion, urinary tract obstruction, sickle cell nephropathy, and amiloride or triamterene use.