Summary. The role of "leakage" of tubular fluid in anuria produced by mercury poisoning was studied in rats by micropuncture techniques. After an initial brisk diuresis, almost all animals were completely anuric 24 hours after HgCl2 injection. Lissamine green injected intravenously in the early stage of anuria appeared in the beginning of the proximal tubule, but the color became progressively lighter as the dye traversed the proximal convolutions. The dye was barely visible in the terminal segments of the proximal tubule; it did not appear at all in the distal tubules. These observations suggest that the proximal epithelium had become abnormally permeable to Lissamine green.Tubular fluid to plasma inulin (TF/PIn) ratios and inulin clearance were measured in individual nephrons at three sites: early proximal tubule, late proximal tubule, and distal tubule. It was found that TF/PN ratios were abnormally low in the late proximal and distal tubules. Inulin clearance was normal at the beginning of the proximal tubule but fell by more than 60% by the late proximal convolutions. Thus, the proximal tubule had also become permeable to inulin.We conclude from these observations that anuria in mercury poisoning can occur in the presence of a normal glomerular filtration rate. The absence of urine flow appears to be due to complete absorption of the filtrate through an excessively permeable tubular epithelium. The driving force affecting this fluid absorption is probably the colloid oncotic pressure of the peritubular capillary blood. IntroductionThe pathologic physiology of anuria in acute renal failure remains obscure in spite of extensive study. The three mechanisms that have been postulated are: a severe reduction in renal blood flow and glomerular filtration rate (GFR), obstruction of the tubules by casts or edema, and excessive

To examine the possible contribution of active H+ secretion mediated by brush border enzymes to proximal tubule HCO-3 absorption, paired reperfusions of surface proximal convoluted tubules were performed with the inhibitor dicyclohexylcarbodiimide (DCCD). In control studies using a solution devoid of HCO-3 but containing 5.5 mM glucose, 1 mM DCCD had no effect on glucose or fluid (Na+) absorption, suggesting that this inhibitor did not interfere with sodium entry at the brush border or mitochondrial energy production (ATP synthesis). In experiments using a perfusion solution containing 18-25 mM HCO-3, DCCD caused a fall in absolute CO2 absorption of approximately 15% under eucapneic conditions and 30% during acute hypercapnia. One millimole per liter amiloride (an inhibitor of the passive Na+-H+ exchanger) caused a 15% inhibition of CO2 absorption during acute hypercapnia and a disproportionately large reduction in fluid (Na+) absorption. The latter was not due to cell poisoning, since 1 mM amiloride had no inhibitory effect on fluid or glucose absorption when a HCO-3-free perfusion solution was used. Addition of 1 mM DCCD to a perfusion solution containing either 10(-3) M amiloride or 10(-4) M acetazolamide caused a significant inhibition of CO2 absorption compared with amiloride or acetazolamide alone. The observations are consistent with the view that in addition to passive Na+-H+ exchange, active transport mediated by either a H+-ATPase or a redox-driven H+ pump in the brush border contributes significantly to HCO-3 absorption in the proximal tubule.

To study proximal tubule bicarbonate absorption that is not due to the neutral Na+-H+ antiporter, mid to late proximal convolutions of the rat kidney were microperfused in vivo with a sodium-free choline solution containing 10(-3) M amiloride. The average sodium concentration resulting from sodium influx was 12 mM. At such low intraluminal [Na+], 10(-3) M amiloride should have inhibited the Na+-H+ antiporter by greater than 95%. When 25 mM HCO3- was in the perfusion fluid, measured total CO2 absorption was 100 pmol.mm-1.min-1. When luminal [HCO3-] was raised to 50 mM, and blood [HCO3-] was also raised to approximately 50 mM to avoid a transepithelial HCO3- concentration gradient, total CO2 absorption increased to greater than 300 pmol.mm-1.min-1. Thus raising intraluminal HCO3- concentration caused a marked increase in total CO2 absorption even though intraluminal [Na+] was low and amiloride was present. Control perfusions containing 140 mM Na+ yielded total CO2 absorption that was approximately 100 pmol.mm-1.min-1 higher than with the respective sodium-free perfusion solutions. In additional experiments, either DCCD or NEM was added to sodium-free perfusion solutions to inhibit H+-ATPase. These inhibitors reduced Na+-H+ independent total CO2 absorption markedly. Our observations suggest that under physiological acid-base conditions, sodium-independent H+ secretion can account for approximately 50% of total HCO3- absorption in mid to late proximal convolutions. This mechanism is stimulated by an increase in ambient HCO(-3) concentration to a degree that might account for the load-dependency of proximal HCO(-3) absorption in these segments of the proximal tubule.(ABSTRACT TRUNCATED AT 250 WORDS)

Experiments were carried out in rats and isolated turtle bladders to study the defect in H+ transport induced by LiCl. After 3-4 days of intraperitoneal LiCl, rats developed urinary findings of "distal" renal tubular acidosis. Proximal tubular fluid pH measured in situ by glass microelectrodes was higher in lithium-treated rats than in acidotic controls. Proximal fluid total CO2 [tCO2] was also higher, and the fraction of tCO2 leaving the proximal tubule was 14 vs. 7% (P less than 0.001). Impaired acidification was also apparent beyond distal convoluted tubules, as judged by normal distal tCO2 reabsorption but increased HCO3(-) in the urine. During NaHCO3 loading, the proximal defect was ameliorated but not the distal. Turtle bladder studies showed that mucosal lithium inhibits H+ secretion secondary to reducing transepithelial electrical potential, presumably by hyperpolarization of the luminal membrane. A similar mechanism may be responsible for lithium's effect on the distal nephron. Inhibition of proximal tubular HCO3(-) reabsorption is probably not attributable to electrical potential changes but might be due to interference of luminal membrane Na+ entry by Li+ and reduced (Na+ + Li+)-H+ exchange.

No abstract