Examination of the mixing hypothesis as an explanation for elevated urinary CO 2 tensions

A B S T RA C T Measurement of urine to blood (U-B) carbon dioxide tension (Pco2) gradient during alkalinization of the urine has been suggested to assess distal H+ secretion. A fact that has not been considered in previous studies dealing with urinary Pco2 is that dissolution of HCO3 in water results in elevation of Pco2 which is directly proportional to the HCO3 concentration. To investigate the interrelationship of urinary HCO3 and urinary acidification, we measured U-B Pco2 in (a) the presence of enhanced H+ secretion and decreased concentrating ability i.e., chronic renal failure (CRF), (b) animals with normal H+ secretion and decreased concentrating ability, Brattleboro (BB) rats, and (c) the presence of both impaired H+ secretion and concentrating ability (LiCl treatment and after release of unilateral ureteral obstruction). At moderately elevated plasma HCO3 levels (30-40 meq/liter), normal rats achieved a highly alkaline urine (urine pH > 7.8) and raised urine HCO3 concentration and U-B Pco2. At similar plasma HCO3 levels, BB rats had a much higher fractional water excretion and failed to raise urine pH, urine HCO3 concentration, and U-B Pco2 normally. At a very high plasma HCO3 (>50 meq/liter), BB rats raised urine pH, urine HCO3 concentration, and U-B Pco2 to the same levels seen in normals. CRF rats failed to raise urine pH, urine HCO3, and U-B Pco2 normally at moderately elevated plasma HCO3 levels; at very high plasma HCO3 levels, CRF rats achieved a highly alkaline urine but failed to raise U-B Pco2. Dogs and patients with CRF were also unable to raise urine pH, urine HCO3 concentration, and U-B Pco2 normally at moderately elevated plasma HCO3 levels. In rats, dogs, and man, U-B Pco2 was directly related to urine HCO3 concentration and inversely related to fractional water excretion. At moderately elevated plasma HCO3 levels, animals with a distal acidification defect failed to raise U-B Pco2; increasing the plasma HCO3 to very high levels resulted in a significant increase in urine HCO3 concentration and U-B Pco2. The observed urinary Pco2 was very close to the Pco2 which would be expected by simple dissolution of a comparable amount of HCO3 in water. These data demonstrate that, in highly alkaline urine, urinary Pco2 is largely determined by concentration of urinary HCO3 and cannot be used as solely indicating distal H+ secretion.

Section: Discussionmentioning

confidence: 86%

The Critical Importance of Urinary Concentrating Ability in the Generation of Urinary Carbon Dioxide Tension

Arruda¹,

Nascimento²,

Mehta³

et al. 1977

“…Rector,Portwood,and Seldin (24), however, in human studies found high CO2 tensions in urines con-taining only minimal quantities of buffer. Upon re-examining their published urinary buffer titration curves (24), it is apparent that a disequilibrium pH of 1.5 to 2.0 would be required to generate the observed urinary C02 tensions. Since disequilibrium pH of this magnitude was not observed in the present study in rats, the possibility that medullary trapping of C02 released in the collecting duct might also contribute to the final C02 tension of the urine must be considered (25).…”

Section: Discussionmentioning

confidence: 99%

The Mechanism of Bicarbonate Reabsorption in the Proximal and Distal Tubules of the Kidney*

Rector¹,

Carter²,

Seldin³

1965

Self Cite

277

Considerable evidence (1-6) has been adduced to support the hypothesis that the reabsorption of filtered HCO3-by the kidney is mediated by a single mechanism, operative in both the proximal and distal portions of the nephron, which involves the secretion of cellular He in exchange for luminal Na+. The secreted Ho reacts with filtered HC03-to form H2CO3, which then decomposes to C02 and H20.Difficulties arise, however, when the details of the process are examined. In the steady state, the rate at which the H2CO3 is removed from the luminal fluid must equal the rate at which H+ is secreted. Walser and Mudge (7) have estimated that for the uncatalyzed dehydration of H2C03 to account for the observed rates of HC03-reabsorption, the steady-state concentration of H2C03 in luminal fluid must be at least tenfold greater than the concentration that would exist were H2C03 in equilibrium with the C02 tension of luminal fluid and plasma. As a result of the excess H2C03, the steady-state pH would be approximately 1 pH U lower than would be predicted from the luminal concentration of HC03-and the C02 tension of plasma, assuming complete equilibration of luminal H2C03 with plasma C02. A marked disequilibrium pH ' would exist.Two lines of evidence have been advanced to support the presence of a disequilibrium pH in the proximal tubule. Rector and Carter (8) perfused single proximal tubules with NaHCO3 * Submitted for publication July 27, 1964; accepted October 29, 1964. Supported in part by a grant from the American Heart Association and in part by grants 5 TI AM-5028 and 5 TI HE-5469 from the National Institutes of Health.'The difference between the actual pH, under conditions where C02 and H2CO0 are not in equilibrium, and the calculated equilibrium pH will be termed "disequilibrium" pH. and estimated the steady-state intraluminal pH from the change in color of various acid-base indicators. The pH was found to be about 1.5 U lower than the predicted equilibrium pH. However, since the color change could result from loss of dyes by either reabsorption or binding to cell proteins, the validity of these results may be questioned. Bank and Aynedjian (9) measured intratubular pH by aspirating tubular fluid into quinhydrone microelectrodes and comparing the readings while the electrode was still in the tubular lumen with the values obtained when the fluid was removed from the tubule and permitted to reach equilibrium. With this technique, they found the intratubular pH to be 2.0 to 2.5 pH U below the equilibrium pH. These results, however, are open to the serious objection that a disequilibrium pH of this magnitude would require the generation of H2CO3 at a rate 10 to 50 times greater than is theoretically possible, as judged from the rate of HC03-reabsorption.The presence of a disequilibrium pH, however, is not a necessary consequence of the hypothesis that H+ secretion mediates HC03-reabsorption. An equilibrium pH could obtain if H2CO3 were rapidly removed from the tubular urine by either of two mechanisms: 1) nonionic diffusion...

“…The carbon dioxide tension (pCO2) of a highly alkaline urine reaches a value substantially higher than that of systemic blood (1)(2)(3)(4)(5)(6)(7)(8). Pitts and Lotspeich (1) proposed that the existence of an appreciable gradient between urine and blood pCO2 was the consequence of distal H+ secretion into bicarbonate-rich tubular urine in the face of delayed carbonic acid dehydration.…”

Section: Introductionmentioning

confidence: 99%

“…That the rise in urinary pCO2 is an intrarenal rather than a postpapillary event, however, does not invalidate the classic notion that distal H+ secretion is largely responsible for the high urinary pCO2 achieved in a highly alkaline urine. Although other explanations have been offered to account for the development of a urine to blood PCO2 gradient (3, 6, 7, 1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17], it is generally accepted that distal H+ secretion largely accounts for this phenomenon (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). The recent finding of a significant disequilibrium pH in the papillary collecting duct under conditions of bicarbonate loading has been proposed as proof of the notion that H+ secretion by the collecting duct is the most likely determinant of the urine minus blood (U-B)' PCO2 gradient observed in an alkaline urine (9).…”

Section: Introductionmentioning

confidence: 99%

“…The use of the U-B pCO2 as a marker of distal H' secretion assumes that blood pCO2 and urine PCO2 are about the same before alkalinization of the urine. There are situations, however, where the urinary pCO2 can be lower than blood pCO2 as in metabolic and respiratory acidosis (3,6,(31)(32)(33). It also assumes that during bicarbonate loading medullary blood pCO2 is similar to that of systemic blood.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Relationship of urinary and blood carbon dioxide tension during hypercapnia in the rat. Its significance in the evaluation of collecting duct hydrogen ion secretion.

Batlle¹,

Downer²,

Gutterman³

et al. 1985

This study was designed to establish the relationship between urinary pCO2 and systemic blood pCO2 during acute hypercapnia and to investigate the significance of this relationship to collecting duct hydrogen ion (He) secretion when the urine is acid and when it is highly alkaline. In rats excreting a highly alkaline urine, an acute increase in blood pCO2 (from 42±0.8 to 87±0.8 mmHg) resulted in a significant fall in urine minus blood (U-B) pCO2 (from 31±2.0 to 16±4.2 mmHg, P < 0.005), a finding which could be interpreted to indicate inhibition of collecting duct H' secretion by hypercapnia. The urinary pCO2 of rats with hypercapnia, unlike that of normocapnic controls, was significantly lower than that of blood when the urine was acid (58±6.3 and 86±1.7 mmHg, P < 0.001) and when it was alkalinized in the face of accelerated carbonic acid dehydration by infusion of carbonic anhydrase (78±2.7 and 87±1.8 mmHg, P < 0.02). The finding of a urinary pCO2 lower than systemic blood pCO2 during hypercapnia suggested that the urine pCO2 prevailing before bicarbonate loading should be known and the blood pCO2 kept constant to evaluate collecting duct H' secretion using the urinary pCO2 technique.In experiments performed under these conditions, sodium bicarbonate infusion resulted in an increment in urinary pCO2 (i.e., a ApCO2) which was comparable in hypercapnic and normocapnic rats (40±7.2 and 42±4.6 mmHg, respectively) that were alkalemic (blood pH 7.53±0.02 and 7.69±0.01, respectively). The U-B pCO2, however, was again lower in hypercapnic than in normocapnic rats (15±4.0 and 39±2.5 mmHg, respectively, P < 0.001). In hypercapnic rats in which blood pH during bicarbonate infusion was not allowed to become alkalemic (738±0.01), the ApCO2 was higher than that of normocapnic rats which were alkalemic (70±5.6 and 42±4.6 mmHg, respectively, P < 0.005) while the U-B pCO2 was about the same (39±3.7 and 39±2.5 mmHg). We further examined urine pCO2 generation by measuring the difference between the urine pCO2 of a highly alkaline urine not containing carbonic anhydrase and that of an equally alkaline urine containing this enzyme. Carbonic anhydrase infusion to hypercapnic rats that were not alkalemic resulted in a fall in urine Portions of this work were presented at the National Meeting of the American Federation of Clinical Research (Washington, DC, 1982 PCO2 (from 122±5.7 to 77±2.2 mmHg) which was greater (P < 0.02) than that seen in alkalemic normocapnic controls (from 73±1.9 to 43±13 mmHg) with a comparable urine bicarbonate concentration and urine nonbicarbonate buffer capacity. CO2 generation, therefore, from collecting duct H+ secretion and titration of bicarbonate, was higher in hypercapnic rats than in normocapnic controls. We conclude that in rats with acute hypercapnia, the U-B PCO2 achieved during bicarbonate loading greatly underestimates collecting duct H+ secretion because it is artificially influenced by systemic blood pCO2. The ApCO2 is a better qualitative index of collecting duct H+ secretion than the ...