Steinmetz P R, Al-Awqati Q, Lawton W J
Am J Med Sci. 1976 Jan-Feb;271(1):40-54. doi: 10.1097/00000441-197601000-00006.
We have discussed two patients who had renal tubular acidosis complicated by hypokalemia. The first patient had a distal acidifying defect. Circumstantial evidence has been presented suggesting that exposure to toluene-diisocyanate or toluene-diamine played a role in the pathogenesis. The acidosis and the hypokalemia of this patient were easily corrected by the administration of small amounts of sodium bicarbonate without potassium supplementation. The second patient had an interstitial nephritis of unknown etiology and presented with moderate renal insufficiency, renal tubular acidosis, and proximal as well as distal acidifying defects. The proximal tubular dysfunction was associated with general aminoaciduria and glucosuria. This patient required large quantities of both alkali and potassium to correct the electrolyte abnormalities. The mechanisms of potassium wasting in proximal and distal renal tubular acidosis are reviewed. A classification is presented of cellular defects that may underlie the different renal acidifying defects. Attempts to distinguish between pump and permeability defects from urinary pCO2 levels must take into account the simultaneous HCO-3 concentration, since large pCO2 elevations require the presence of ample HCO-3 in the urine. Permeability defects may impair urinary acidification by either abnormal back flux of H+ out of the lumen or increased influx of HCO-3 into the lumen. In studies of acidification in vitro, amphotericin B causes increased H+ permeability and has little effect on HCO-3 permeability. Toluene-diamine causes a marked permeability defect which is reversible, but remains to be defined in terms of the ion species, HCO-3 or H+, affected. At times, hyperchloremic acidosis is caused by distal defects in net acid excretion that occur without impairment of the H+ gradient. In certain patients with hypoaldosteronism, for example, distal H+ secretion may be reduced without change in the force of the H+ pump.
我们讨论了两名患有肾小管酸中毒并伴有低钾血症的患者。第一名患者存在远端酸化缺陷。已有间接证据表明，接触甲苯二异氰酸酯或甲苯二胺在发病机制中起了作用。该患者的酸中毒和低钾血症通过给予少量碳酸氢钠而无需补充钾即可轻松纠正。第二名患者患有病因不明的间质性肾炎，表现为中度肾功能不全、肾小管酸中毒以及近端和远端酸化缺陷。近端肾小管功能障碍与全身性氨基酸尿和糖尿有关。该患者需要大量的碱和钾来纠正电解质异常。本文回顾了近端和远端肾小管酸中毒中钾耗竭的机制。提出了一种可能是不同肾脏酸化缺陷基础的细胞缺陷分类。试图根据尿液pCO2水平区分泵缺陷和通透性缺陷时，必须考虑同时存在的HCO-3浓度，因为pCO2大幅升高需要尿液中有充足的HCO-3。通透性缺陷可能通过H+从管腔异常回流或HCO-3进入管腔增加而损害尿液酸化。在体外酸化研究中，两性霉素B会导致H+通透性增加，而对HCO-3通透性影响很小。甲苯二胺会导致明显的通透性缺陷，这种缺陷是可逆的，但仍有待根据受影响的离子种类（HCO-3或H+）来确定。有时，高氯性酸中毒是由净酸排泄的远端缺陷引起的，而这种缺陷并不伴有H+梯度的受损。例如，在某些醛固酮缺乏症患者中，远端H+分泌可能减少，而H+泵的力量没有改变。
