Validation of the difference in urine and blood carbon dioxide tension during bicarbonate loading as an index of distal nephron acidification in experimental models of distal renal tubular acidosis (original) (raw)

Clinical review: Renal tubular acidosis--a physicochemical approach

Critical care (London, England), 2005

The Canadian physiologist PA Stewart advanced the theory that the proton concentration, and hence pH, in any compartment is dependent on the charges of fully ionized and partly ionized species, and on the prevailing CO2 tension, all of which he dubbed independent variables. Because the kidneys regulate the concentrations of the most important fully ionized species ([K+], [Na+], and [Cl-]) but neither CO2 nor weak acids, the implication is that it should be possible to ascertain the renal contribution to acid-base homeostasis based on the excretion of these ions. One further corollary of Stewart's theory is that, because pH is solely dependent on the named independent variables, transport of protons to and from a compartment by itself will not influence pH. This is apparently in great contrast to models of proton pumps and bicarbonate transporters currently being examined in great molecular detail. Failure of these pumps and cotransporters is at the root of disorders called renal...

The regulation of renal acid secretion: New observations from studies of distal nephron segments

Kidney International, 1986

Forty years ago, in a landmark paper, Pitts and Alexander [1] proposed that the renal excretion of acid is accomplished by 'a single fundamental process based primarily on the exchange of H ions for Na ions". Ten years later, Schwartz, Jenson and Relman [21 demonstrated that the acute infusion of sodium sulphate in humans ingesting a low sodium chloride diet was associated with a dramatic fall in urine pH, although systemic acid-base balance was not changed. The observation that hydrogen ion excretion can increase without a fall in blood pH has been relentlessly pursued by Schwartz and his colleagues [2]. Many meticulous chronic steady-state experiments have provided results which have been explained by a "non-homeostatic" hypothesis, elegantly presented by Schwartz and Cohen [3]. This view, to which we will hereafter refer as the cation exchange hypothesis, states that it is not blood pH but changes in sodium delivery, sodium avidity, and subsequent "Na-H exchange" of the distal nephron which determine the rate of renal hydrogen ion secretion. Chloride depletion or chloride substitution with less permeable anions are considered to also influence the rate of "Na-H exchange". Some of the situations studied by Schwartz and his colleagues include: alkalinization of systemic blood in chronic metabolic alkalosis, the different degrees of acidosis observed with chronic infusion of mineral acids of different anions, the normal bicarbonate concentration observed during vasopressin-induced volume expansion, and the induction of metabolic alkalosis by the administration of potassium and a non-reabsorbable anion to sodium and potassium depleted animals [4-8]. All have been explained on the basis of altered intrarenal sodium handling, subsequent stimulation of hydrogen ion secretion, and enhanced bicarbonate reabsorption. It is important to emphasize that this cation exchange hypothesis characterizes distal nephron H secretion as being uninfluenced by blood pH, but responsive primarily to Na handling and anion movements. Not surprisingly, such a comprehensive approach has strongly influenced current views on the renal regulation of acid-base balance. Recently, new studies have been completed which enable us to reconsider whether the regulation of hydrogen ion secretion "Na-H exchange" does not refer to any single mechanism but rather to some linkage (direct or indirect) between Na absorption and H secretion

Distal renal tubular acidosis with intact capacity to lower urinary pH

The American Journal of Medicine, 1982

The sine qua non for the diagnosis of distal renal tubular acidosis requires that the urinary pH cannot decrease maximally during systemic acidosis. A defect in distal acidtficatlon however, could also result from a decrease in the capacity (or rate) of distal hydrogen ion secretion. In thls type of defect, the abtltty to lower the urlnary pH during acfdemia could be preserved as long as a certain capacity for hydrogen ion secretion remained. In this report, we describe four patients with deranged distal urlnary acidtfication, in whom urinary pH was able to decrease (4.99 f O.ll)l during acidemia. One of the patients had hyperchloremic metabolic acidosis whereas the remaining three were not spontaneously ~acidotic. In these patients, the defect for distal urinary acldiflcation was disclosed by the inabtltty of the urine-btood pCO2 gradlent ~ to increase normally (i.e., above 30 mm Hg) during btcarbonatel loading. In contrast, a normal Increase in the urine-blood pCOn gradient was observed in each patient in response to neutral sodium phosphate infusion. The reabsorptlve capacity of bicarbonate was not depressed in these patients, which indicated that the acidfficatlon process in the proxtmat nephron was intact. We propose that our four patients had a defect in distal urinary acidlficatlon caused by a reduction in the rate of distal hydrogen ion secretion rather than an inabiltty to generate a steep pH gradient across the distal nephron. Our data atso suggest that the tnabtttty to raise urtnary pC@ normally during sodium bicarbonate loading may be the most sensitive index of decreased distal urinary acidtflcatlon available.

Effect of blood pH on distal nephron hydrogen ion secretion

Kidney International, 1980

Effect of blood pH on distal nephron hydrogen ion secretion. The purpose of this study was to determine the effect of changes in blood hydrogen ion concentrations on urine acidification. The urine minus the blood Pco2 gradient in alkaline urine was used to monitor distal nephron hydrogen ion secretion. To obtain alkaline urine during acidemia, we induced proximal renal tubular acidosis by lysine. The urine minus the blood Pco2 gradient was evaluated relative to the urine bicarbonate concentration over a range of blood pH values. For any given urine bicarbonate concentration, the urine minus the blood Pco2 gradient was directly related to the blood hydrogen ion concentration. Conclusions. Acidemia stimulates and alkalemia inhibits distal nephron hydrogen ion secretion. Because the slope relating the urine minus the blood Pco2 gradient to the urine bicarbonate concentration was much steeper in urine from acidemic dogs, this change in relationship cannot be explained by a simple chemical equilibrium of the bicarbonate buffer system. Effet du pH sanguin sur Ia sécrétion d'ion hydrogène par le néphron distal. Le but de ce travail est de determiner l'effet des modifications de la concentration sanguine des ions hydrogène sur l'acidification de l'urine. Le gradient de Pco2 urine moms sang en urine alcaline a été utilisé pour évaluer la sécrétion d'ions hydrogène par le néphron distal. Afin d'obtenir une urine alcaline au cours de l'acidémie, une acidose tubulaire proximale a été induite par Ia lysine. Le gradient de Pco2 urine moms sang a été évalué en fonction de Ia concentration de bicarbonate dans un éventail de valeurs de pH du sang. Pour une concentration de bicarbonate de l'urine donnée le gradient est directement lie a Ia concentration d'ions hydrogène dans le sang. Conclusions. L'acidémie stimule et l'alcalémie inhibe Ia sécrétion distale d'ions hydrogène. Puisque Ia pente qui relie le gradient de Pco2 urine moms sang a Ia concentration de bicarbonate de l'urine est beaucoup plus grande dans l'urine de chiens acidémiques, une simple modification de l'equilibre chimique du système tampon bicarbonate ne peut expliquer Ia modification de la relation.

Lithium-induced impairment of urine acidification

Kidney International, 1976

Lithium-induced impairment of urine acidifcation. The purpose of this study was to clarify the means by which lithium induced a disorder of urine acidification. Rats infused with hydrochloric acid (I mEq/kg) developed acute metabolic acidosis (blood pH = 7.32; bicarbonate, 8 mEq/liter) with a urine pH of approximately 5.85. The addition of lithium chloride (4 mEq/kg i.p.) caused an increase in the urine p1-I (6.38) and a further decrease in blood bicarbonate (11.0 mEq/liter). During bicarbonate loading, lithium caused the urine Pco2 to fall significantly (urine minus blood Pco2 decreased from 25.3 + 2.8 to 14.4 2.3 mm Hg). These changes were not seen following equimolar i.p. administration of sodium chloride. Similarly, lithium administration depressed bicarbonate reabsorption by 11.1% (from 30.6 to 27.2 iEq/ml of GFR) during alkali infusion, while saline caused only a 5% decrease (30.0 to 28.5 pEq/rnl of GFR). The combination of an increase in urine pH and bicarbonate excretion during acidosis and a decrease in urine Pco2 in alkaline urine indicates that lithium produced a defect in distal nephron hydrogen ion secretion. The fall in bicarbonate reabsorption following lithium administration could be due to a mild hydrogen ion secretory defect located in the proximal tubule or a severe defect in the distal nephron. Alteration de l'acidification de l'urine induite par le lithium. Le hut de ce travail est de melttre en evidence les mécanismes par lesquels le lithium induit un dCsordre de l'acificiation des urines. Des rats perfusCs avec de l'acide chlorhydrique (1 mEq/kg) développent une acidose metabolique aiguë (p1-I sanguin = 7,32, hicarbonates plasmatiques 18 mEq/litre) avec un pH urinaire voisin de 5,85. L'administration de chlorure de lithium (4 mhq/kg i.p.) determine one augmentation du p1-I de l'urine (6,38) et une diminution des bicarbonates plasmatiques (11,0 mEq/liter). Au cours d'une charge de bicarbonate le lithium determine une diminution significative de Ia Pco2 de l'urine (Ia difference de Pco2 urine moms sang décroIt de 25,3 + 2,8 C 14,4 2,3 mm Hg). Ces modifications ne sont pas observées si du sodium est administré C Ia place du lithium, par voie intra-péritonéale et de facon équimolaire. L'administration de lithium déprime Ia reabsorption des bicarbonates de I 1.1% (de 30,6 C 27,2 iEq/ml GFR) au cours d'une perfusion alcaline alors qu'une perfusion saline ne determine qu'une diminution de 5% (30,0 a 28,5 mEq/ml GFR). Lassociation dune augmentation du p1-I de lurine et d'une auginentation de l'excrétion des bicarbonates au coors de l'acidose et dune diminution de Ia Pco2 dans l'urine alcaline indique que le lithium determine un deficit de Ia secretion distale d'ions H. La diminution de Ia reabsorption des bicarbonates consecutive a l'adniinistration de lithium peut être Ia consequence soit d'un deficit modéré de secretion proximale d'ions I-U soit dun deficit distal important.

Kinetics of luminal acidification in cortical tubules of the rat kidney

1977

1. Some kinetic aspects of renal tubular acidification were studied in proximal and distal tubules of the rat kidney by combining stationary m~croperfusion methods and continuous measurements of luminal pH changes of phosphate or bicarbonate buffers by means of antimony electrodes. The analysis included the measurement of steady-state pH, steady-state buffer concentrations and acidification half-times. From these data, net rates of tubular bicarbonate reabsorption and of H ion secretion were obtained since it was shown that the rate of phosphate acidification provides a realistic estimate of H ion secretion.