Characterization of distal hydrogen in acute respiratory alkalosis
ion secretion
J. TIMOTHY SEHY, MELVIN K. ROSEMAN, JOSE A. L. ARRUDA, AND NEIL A. KURTZMAN Sections of Nephrology, University of Illinois Abraham Lincoln School of Medicine, and Veterans Administration West Side Hospital, Chicago, Illinois 60612 SEHY,
J.
TIMOTHY,
MELVIN
K.
ROSEMAN,
JOSE
A. L.
ARRUDA, AND NEIL A. KURTZMAN. Characterization of distal hydrogen ion secretion in acute respiratory alkalosis. Am. J. Physiol. 235(3): F203-F208, 1978 or Am. J. Physiol.: Renal Fluid Electrolyte Physiol. 4(3): F203-F208, 19’78. -The effect
of acute respiratory alkalosis (ARA) on distal nephron H+ secretion was evaluated by measuring urine-to-blood (U-B) PCO,in dogs with highly alkaline urine (urine pH > 7.8). ARA led to a significant decreasein U-B Pcoz and in urine HCO, concentration; urine pH, however, increased significantly, indicating that the decrease in urine Pco, was of greater magnitude than the decreasein urine HC03 concentration. For any given urine HCO, concentration urine Pco2 was lower (i.e., urine pH was higher) in ARA than in controls. Administration of tris (hydroxymethyl)aminomethane (Tris) during ARA resulted in a significant increase in U-B PCO, to control values. In animals with moderately alkaline urine (urine pH 6.4-7.4) and high urine PO, concentration, ARA resulted in a significant decreasein U-B Pco, and urine PO, concentrations. Neutral PO, infusion in these dogs resulted in an increase in urine PO, concentration and U-B PCO,to control levels. These data demonstrate that ARA results in a significant decreasein U-B Pco2 that is not solely attributable to changes in urine HCO, concentration. The observation that Tris and PO, infusion during ARA raises UB Pcoz to control levels suggeststhat the ability to secreteH+ is intact.
tion of U-B Pcoz gradient
during alkalinization of the urine as well as to determine to what extent the low UB Pcoz is due to a reduction in urinary HCOs concentration rather than to an acidification defect. MATERIALS
AND
METHODS
All experiments were performed on female mongrel dogs weighing 15-25 kg. The dogs were anesthetized with an intravenous injection of sodium pentobarbital, 30 mg/kg body wt; light anesthesia, as judged by cornea1 reflexes, was maintained by subsequent small doses. An endotracheal tube was inserted and connected to a Bird respirator. Pco2 was maintained at the desired level by appropriate manipulation of the respirator. A 21.gauge butterfly needle was inserted into a femoral artery to record blood pressure and to sample blood. A peripheral vein needle was used to infuse 0.9% saline containing [1251]iothalamate (40 &i/liter) at a rate of 0.6 ml/min throughout the experiment as a marker of glomerular filtration rate (GFR). NaHC03 was infused at varying rates to achieve the desired urine pH. An equilibration period of 40-60 min was allowed before collection was started. Collection periods were of 10 min duration. Urine was collected via an indwelling Foley catheter. The following groups distal H+ secretion; urine-blood Pcop gradient; Tris, P04, and were studied. H+ secretion Group IA: ARA followed by tris(hydroxymethyl)aminomethane infusion, high plasma HCO,. Ten dogs were infused with 0.9 M NaHCO, at varying rates to ACUTE RESPIRATORYALKALOSIS (ARA)resultsindepresachieve a stable plasma HCO, above 30 meq/liter and a sion of HCOs reabsorption in the proximal tubule and urine pH between 7.8 and 8.1; plasma Pco, was mainincreased excretion of HC03, Na, and K in the final tained between 35 and 40 mmHg. Three control collecurine (4, 16, 17). The effect of ARA on distal nephron tions were obtained. Respiratory alkalosis was then H+ secretion has been difficult to evaluate since the induced by manipulating the respirator until the Pcoz increased distal delivery of HCO, induced by hypocapwas stabilized at 18-25 mmHg. We allowed at least 45 nia results in decreased titratable acid and NH, excre- min for equilibration before collections were started. tion due to the elevation of the urine pH (4, 17). Three collections were obtained. After this tris(hyRecently Giammarco et al. (8) examined the effect of droxymethyl)aminomethane (Tris) was infused with a 1 mmol/kg body weight intravenous bolus followed by a ARA on the urine-to-blood (U-B) Pcoz gradient during alkalinization of the urine. They concluded that ARA 1 mmol/min infusion during which three more clearance collections were obtained. decreases U-B Pco2 through inhibition of H+ secretion in the collecting duct (7, 9). We have recently demonGroup IB: moderate plasma HCO, concentration. strated that U-B Pco2 in highly alkaline urine is Five dogs were infused with 0.9 M NaHCO, as ingroup largely determined by urine HCOs concentration and IA for control clearance collections. The HCO, infusion not solely by urinary acidification (2). This study was was then stopped and replaced by 0.9% saline; respiratory alkalosis was induced as above, and after at least undertaken to evaluate the role of ARA in the genera036306127/78/0000-0000$01.25 Copyright
0 1978 the American
Physiological
Society
F203
Downloaded from www.physiology.org/journal/ajprenal by ${individualUser.givenNames} ${individualUser.surname} (128.143.007.175) on November 16, 2018. Copyright © 1978 the American Physiological Society. All rights reserved.
SEHY,ROSEMAN,
F204 45 .min of hyperventilation three clearance collections were run. Tris was infused as in group IA for the final three periods. Group II: Tris infusion + ARA. Five dogs were infused with 0.9 M NaHCO, as described above. When the urine pH was greater than 7.8, three clearance collections were run. Tris was then infused at a bolus dose of 1 mmol/kg followed by infusion at 1 mmol/min. Three collections were obtained. ARA was then induced and three additional collections were obtained aRer at least 45 min of stabilization. Group III: neutral PO, infusion during ARA. Four normal dogs were prepared for clearance study as described above. Following three control collections ARA was induced as described. NH&l (1.5%) was . infused at varying rates in order to keep a stable urine pH in the range of 6.4-7.4. When urine pH and plasma PC% were stable for at least 45 min, three clearance collections were obtained. Neutral PO, solution (Na2HP0, and NaH2P0 4 in a molar ratio of 4:l) was then infused at a rate of 100 Fmol/min for 60 min, and three final collections were obtained in the last 30 min of PO, infusion. Specimen collection, GFR, plasma and urinary electrolyte determinations, and statistical analyses were performed and calculated as previously described (12). Carbonic anhydrase in the urine was measured by the method described by Maren (13). Data are presented as means t SE. The values presented in the tables represent the means of two or three clearance periods. RESULTS
Table 1 and Fig. 1 present the data from group IA. Administration of NaHCO, to normal dogs resulted in the elevation of U-B Pco~. Following hyperventilation blood pH increased from 7.55 t 0.02 to 7.76 t 0.03 (P c TABLE
1. Effect of acute respiratory Gm,
C
v,
pi.li!iz~a
alkalosis Plasma p-2, -Hg
0.001). ARA resulted in a significant decrease in U-B Pcoz and an increase in urine pH (Fig. 1). Urine HCOs concentration also decreased significantly (Table 1 and Fig. 1). GFR and maximum HCOs reabsorption per liter GFR (T,,,HCO$GFR) also decreased significantly. Fractional excretion (FE) of Na and FEK increased significantly, whereas FEcl remained unchanged. Administration of Tris during ARA resulted in a significant increase in U-B Pco, and in a decrease in urine pH. The values of U-B PcoB observed during Tris administration were not significantly different from those observed during control. Tris administration resulted in a significant increase in FENa, FEK, and FEcl. T,,,HCOJGFR, plasma HC03, and urine HCOs were unchanged during Tris administration. In order to determine whether the decrease in U-B Pco2 during ARA was due to inhibition of H+ secretion because the urine was very alkaline and the blood pH was very high, studies were performed to minimize these changes. Table 1 shows that discontinuation of NaHCO, infusion during ARA resulted in a decrease in HCO, concentration in both the urine and plasma. Blood pH increased from 7.52 t 0.02 to 7.67 t 0.01 (P c 0.01). Despite the fact that changes in blood and urine pH were decreased as compared to the previous group, ARA again led to a significant decrease in U-B Pcoz. Tris administration increased U-B Pco2 significantly. There was no carbonic anhydrase activity detectable in the urine samples of dogs either during control or during ARA. Figure 2 plots urine HCOs concentration against urine pH. Pco2 isobars are also shown in this figure. The points of groups IA and IB are plotted. It is clear that within a range of comparable urine HCO, concentrations urine Pco2 was lower (therefore urine pH was higher) in ARA than during normocapnia. Accordingly,
on U-B PC02 Urine Pw, -Hg
U-B Pm, mmHg
39.9 + 0.22
67.6 f 6.44
27.5 2 4.66
30.1 f 1.52
21.6 f 0.82
37.4 f 3.89
15.8 f 3.46
2.7 f 0.38
31.7 + 0.89
23.5 + 0.88
65.6 f 6.04
32.1 f 5.86
1.4 f 0.61
29.9 + 0.81
37.9 + 1.38
64.3 + 3.02
26.4 f 2.60
23.1 f 0.76
20.4 f 0.71
39.6 f 3.19
ml/min
mUmin
60.9 f 2.91
2.2 f 0.44
34.2 k 1.33
39.0 f 6.01
1.6 2 0.41
35.6 f 3.67
meq&r
ARRUDA, AND KURTZMAN
Urine HCOs, meq/litcw
%,JxH~W
7.94 f 0.03
166.6 f 18.83
8.12 f 0.04
126.8 f 19.36
Urine
pH
F&c, 96
F&I, 96
28.2 f 1.64
61.6 A 7.41
1.3 + 0.47
24.6 f 1.68
92.6 f 12.62
0.8 + 0.28
meq/lijer
P
C
62.3 f 7.68
Trill Valuea zFyn
23.6 f 1.36
132.6 f 10.71
CO.06
NS
NS
CO.06
CO.06
CO.06
44.0 A 6.92
3.7 2 0.84
27.3 f 0.98
20.7 + 0.72
61.4 f 10.63
40.7 f 10.08
7.77 f 0.03
71.9 + 6.70
38.8 + 6.49
48.3 & 6.21
79.3 f 9.82
co.02
are meana * SE of two or three clearance pkr liter GFR; m, fraction&l excretion . * Infu8ed in nine animala.
26.8 f 0.71
20.7 f 1.61
periods. Abbreviations: GFR, glomendar filtration rate; V, urine flow; U-B, urine-to-blood gradient; of potassium; F&, fractional excmtion of chloride; C, control; RA, respiratory alkaloeie. P valuea r&r
103.0 f 4.61 T-HCOJGFR, to compardn
2.4 f 1.01 bicarbonate to the pvioue
Downloaded from www.physiology.org/journal/ajprenal by ${individualUser.givenNames} ${individualUser.surname} (128.143.007.175) on November 16, 2018. Copyright © 1978 the American Physiological Society. All rights reserved.
H+ SECRETION
AND
ACUTE
RESPIRATORY
F205
ALKALOSIS
60s x FIG. 1. U-B Pcop (A), urine HCO, concentration (B), and urine pH (C) during control, acute respiratory alkalosis, and acute respiratory alkalosis + Tris infusion. Points of Group IA are shown.
E
-
so-
E
$bO-
s &
30-
I
’
1
C
RA
I
I
RA+TRIS
-
C
RA
RA+TRIS
C
RA
RA+TRIS
ARA resulted in a significant decrease in U-B Pco, and urine PO, concentration. Infusion of neutral PO, resulted in an increase in U-B Pco2 and urine PO, to control levels. DISCUSSION
60
80
loo
I20
URINE
I40
HCO,
I60
180
200
220
240
260
200
(mEq/J)
FIG. 2. Interrelationship of urine pH, urine HC03 concentration, and urine Pco2. Points of Groups IA and IB are plotted. For any given urine HCO, concentration, urine. pH was higher (i.e., urine PCO, was lower) in respiratory alkalosis than in controls.
the decline in U-B Pco2 seen during ARA cannot be attributed to the decrease in urine HCO, concentration. Table 2 shows the effect of Tris administration on normal dogs with highly alkaline urine. Tris administration resulted in a significant increase in U-B Pco2, a decrease in urine pH, and an unchanged urine HCO, concentration. Urine flow, FEK, and FEN, also increased significantly. Induction of ARA during Tris administration resulted in a small decrease in U-B PC%; urine pH increased slightly but the increase did not achieve statistical significance. GFR and TmaxHCOJ GFR decreased significantly during ARA. FEN, and FEK increased significantly during ARA. Table 3 shows the results obtained during neutral PO, infusion in animals with ARA. During control periods U-B Pcoz was high despite the fact that the urine pH was only 6.39. This high U-B Pco2 is probably due to the high urine* PO, concentration. Induction of
ARA is well known to result in depression of HCOs reabsorption in the proximal tubule and to increase excretion of NaHC03 and K in the final urine (4, 16, 17). The effect of ARA on collecting duct H+ secretion has been difficult tc evaluate, since the increased delivery of HCO, to the collecting duct results in decreased net acid excretion. Chronic respiratory alkalosis is associated with a decrease in NH, excretion which is thought to be secondary to inhibition of distal nephron H+ secretion (7). Giammarco et al. (8) have demonstrated that ARA leads to a decrease in U-B Pcoz during alkalinization of the urine. They interpreted these data as indicating inhibition of H+ secretion in the collecting duct during ARA. It should be pointed out that this conclusion was based solely on the fact that ARA led to a decrease in U-B Pcoz; no other parameter of H+ secretion in the collecting duct was evaluated. We have recently demonstrated that in highly alkaline urine Pco2 is largely determined by urinary concentration and not by urinary acidification. It was necessary, therefore, to determine to what extent the decrease in U-B Pco2 seen in respiratory alkalosis was due to a reduction in urine HCO, concentration rather than to an acidification defect (2, 19). Our data confirm the observation of Giammarco et al. (8) that ARA leads to a consistent decline in urinary Pco2. Our data also demonstrate that ARA causes a decrease in urinary HCO, concentration and an increase in urine pH. Theoretically the decrease in urinary HCO, concentration could be the primary event and thereby lead to a decrease in urinary Pco~, or conversely, the decrease in urinary PCO, could be the primary event and result in a decrease in HCO, concentration due to a shifi to the right in the equilibrium in the following reaction
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SEHY, ROSEMAN, ARRUDA, AND KURTZMAN
F206 TABLE
2. Effect of Tris on U-B PCO~ before and during GFR, ml/min
Plasma pco,, -Hg
v, ml/min
acute respiratory
urine Pcq, mmHg
Urine
alkalosis pH
Urine HCOs, meq/liter
FEK,
%
?*
Gmup II (n = 6) c
69.6 f 3.67
1.2 f 0.36
29.9 f 1.16
40.0 f 1.43
P
NS
eO.06
NS
NS
67.2 f 6.36
2.8 + 0.64
32.7 f 1.46
37.6 -e 0.86
CO.06
NS
eo.01
ion secretion
J. TIMOTHY SEHY, MELVIN K. ROSEMAN, JOSE A. L. ARRUDA, AND NEIL A. KURTZMAN Sections of Nephrology, University of Illinois Abraham Lincoln School of Medicine, and Veterans Administration West Side Hospital, Chicago, Illinois 60612 SEHY,
J.
TIMOTHY,
MELVIN
K.
ROSEMAN,
JOSE
A. L.
ARRUDA, AND NEIL A. KURTZMAN. Characterization of distal hydrogen ion secretion in acute respiratory alkalosis. Am. J. Physiol. 235(3): F203-F208, 1978 or Am. J. Physiol.: Renal Fluid Electrolyte Physiol. 4(3): F203-F208, 19’78. -The effect
of acute respiratory alkalosis (ARA) on distal nephron H+ secretion was evaluated by measuring urine-to-blood (U-B) PCO,in dogs with highly alkaline urine (urine pH > 7.8). ARA led to a significant decreasein U-B Pcoz and in urine HCO, concentration; urine pH, however, increased significantly, indicating that the decrease in urine Pco, was of greater magnitude than the decreasein urine HC03 concentration. For any given urine HCO, concentration urine Pco2 was lower (i.e., urine pH was higher) in ARA than in controls. Administration of tris (hydroxymethyl)aminomethane (Tris) during ARA resulted in a significant increase in U-B PCO, to control values. In animals with moderately alkaline urine (urine pH 6.4-7.4) and high urine PO, concentration, ARA resulted in a significant decreasein U-B Pco, and urine PO, concentrations. Neutral PO, infusion in these dogs resulted in an increase in urine PO, concentration and U-B PCO,to control levels. These data demonstrate that ARA results in a significant decreasein U-B Pco2 that is not solely attributable to changes in urine HCO, concentration. The observation that Tris and PO, infusion during ARA raises UB Pcoz to control levels suggeststhat the ability to secreteH+ is intact.
tion of U-B Pcoz gradient
during alkalinization of the urine as well as to determine to what extent the low UB Pcoz is due to a reduction in urinary HCOs concentration rather than to an acidification defect. MATERIALS
AND
METHODS
All experiments were performed on female mongrel dogs weighing 15-25 kg. The dogs were anesthetized with an intravenous injection of sodium pentobarbital, 30 mg/kg body wt; light anesthesia, as judged by cornea1 reflexes, was maintained by subsequent small doses. An endotracheal tube was inserted and connected to a Bird respirator. Pco2 was maintained at the desired level by appropriate manipulation of the respirator. A 21.gauge butterfly needle was inserted into a femoral artery to record blood pressure and to sample blood. A peripheral vein needle was used to infuse 0.9% saline containing [1251]iothalamate (40 &i/liter) at a rate of 0.6 ml/min throughout the experiment as a marker of glomerular filtration rate (GFR). NaHC03 was infused at varying rates to achieve the desired urine pH. An equilibration period of 40-60 min was allowed before collection was started. Collection periods were of 10 min duration. Urine was collected via an indwelling Foley catheter. The following groups distal H+ secretion; urine-blood Pcop gradient; Tris, P04, and were studied. H+ secretion Group IA: ARA followed by tris(hydroxymethyl)aminomethane infusion, high plasma HCO,. Ten dogs were infused with 0.9 M NaHCO, at varying rates to ACUTE RESPIRATORYALKALOSIS (ARA)resultsindepresachieve a stable plasma HCO, above 30 meq/liter and a sion of HCOs reabsorption in the proximal tubule and urine pH between 7.8 and 8.1; plasma Pco, was mainincreased excretion of HC03, Na, and K in the final tained between 35 and 40 mmHg. Three control collecurine (4, 16, 17). The effect of ARA on distal nephron tions were obtained. Respiratory alkalosis was then H+ secretion has been difficult to evaluate since the induced by manipulating the respirator until the Pcoz increased distal delivery of HCO, induced by hypocapwas stabilized at 18-25 mmHg. We allowed at least 45 nia results in decreased titratable acid and NH, excre- min for equilibration before collections were started. tion due to the elevation of the urine pH (4, 17). Three collections were obtained. After this tris(hyRecently Giammarco et al. (8) examined the effect of droxymethyl)aminomethane (Tris) was infused with a 1 mmol/kg body weight intravenous bolus followed by a ARA on the urine-to-blood (U-B) Pcoz gradient during alkalinization of the urine. They concluded that ARA 1 mmol/min infusion during which three more clearance collections were obtained. decreases U-B Pco2 through inhibition of H+ secretion in the collecting duct (7, 9). We have recently demonGroup IB: moderate plasma HCO, concentration. strated that U-B Pco2 in highly alkaline urine is Five dogs were infused with 0.9 M NaHCO, as ingroup largely determined by urine HCOs concentration and IA for control clearance collections. The HCO, infusion not solely by urinary acidification (2). This study was was then stopped and replaced by 0.9% saline; respiratory alkalosis was induced as above, and after at least undertaken to evaluate the role of ARA in the genera036306127/78/0000-0000$01.25 Copyright
0 1978 the American
Physiological
Society
F203
Downloaded from www.physiology.org/journal/ajprenal by ${individualUser.givenNames} ${individualUser.surname} (128.143.007.175) on November 16, 2018. Copyright © 1978 the American Physiological Society. All rights reserved.
SEHY,ROSEMAN,
F204 45 .min of hyperventilation three clearance collections were run. Tris was infused as in group IA for the final three periods. Group II: Tris infusion + ARA. Five dogs were infused with 0.9 M NaHCO, as described above. When the urine pH was greater than 7.8, three clearance collections were run. Tris was then infused at a bolus dose of 1 mmol/kg followed by infusion at 1 mmol/min. Three collections were obtained. ARA was then induced and three additional collections were obtained aRer at least 45 min of stabilization. Group III: neutral PO, infusion during ARA. Four normal dogs were prepared for clearance study as described above. Following three control collections ARA was induced as described. NH&l (1.5%) was . infused at varying rates in order to keep a stable urine pH in the range of 6.4-7.4. When urine pH and plasma PC% were stable for at least 45 min, three clearance collections were obtained. Neutral PO, solution (Na2HP0, and NaH2P0 4 in a molar ratio of 4:l) was then infused at a rate of 100 Fmol/min for 60 min, and three final collections were obtained in the last 30 min of PO, infusion. Specimen collection, GFR, plasma and urinary electrolyte determinations, and statistical analyses were performed and calculated as previously described (12). Carbonic anhydrase in the urine was measured by the method described by Maren (13). Data are presented as means t SE. The values presented in the tables represent the means of two or three clearance periods. RESULTS
Table 1 and Fig. 1 present the data from group IA. Administration of NaHCO, to normal dogs resulted in the elevation of U-B Pco~. Following hyperventilation blood pH increased from 7.55 t 0.02 to 7.76 t 0.03 (P c TABLE
1. Effect of acute respiratory Gm,
C
v,
pi.li!iz~a
alkalosis Plasma p-2, -Hg
0.001). ARA resulted in a significant decrease in U-B Pcoz and an increase in urine pH (Fig. 1). Urine HCOs concentration also decreased significantly (Table 1 and Fig. 1). GFR and maximum HCOs reabsorption per liter GFR (T,,,HCO$GFR) also decreased significantly. Fractional excretion (FE) of Na and FEK increased significantly, whereas FEcl remained unchanged. Administration of Tris during ARA resulted in a significant increase in U-B Pco, and in a decrease in urine pH. The values of U-B PcoB observed during Tris administration were not significantly different from those observed during control. Tris administration resulted in a significant increase in FENa, FEK, and FEcl. T,,,HCOJGFR, plasma HC03, and urine HCOs were unchanged during Tris administration. In order to determine whether the decrease in U-B Pco2 during ARA was due to inhibition of H+ secretion because the urine was very alkaline and the blood pH was very high, studies were performed to minimize these changes. Table 1 shows that discontinuation of NaHCO, infusion during ARA resulted in a decrease in HCO, concentration in both the urine and plasma. Blood pH increased from 7.52 t 0.02 to 7.67 t 0.01 (P c 0.01). Despite the fact that changes in blood and urine pH were decreased as compared to the previous group, ARA again led to a significant decrease in U-B Pcoz. Tris administration increased U-B Pco2 significantly. There was no carbonic anhydrase activity detectable in the urine samples of dogs either during control or during ARA. Figure 2 plots urine HCOs concentration against urine pH. Pco2 isobars are also shown in this figure. The points of groups IA and IB are plotted. It is clear that within a range of comparable urine HCO, concentrations urine Pco2 was lower (therefore urine pH was higher) in ARA than during normocapnia. Accordingly,
on U-B PC02 Urine Pw, -Hg
U-B Pm, mmHg
39.9 + 0.22
67.6 f 6.44
27.5 2 4.66
30.1 f 1.52
21.6 f 0.82
37.4 f 3.89
15.8 f 3.46
2.7 f 0.38
31.7 + 0.89
23.5 + 0.88
65.6 f 6.04
32.1 f 5.86
1.4 f 0.61
29.9 + 0.81
37.9 + 1.38
64.3 + 3.02
26.4 f 2.60
23.1 f 0.76
20.4 f 0.71
39.6 f 3.19
ml/min
mUmin
60.9 f 2.91
2.2 f 0.44
34.2 k 1.33
39.0 f 6.01
1.6 2 0.41
35.6 f 3.67
meq&r
ARRUDA, AND KURTZMAN
Urine HCOs, meq/litcw
%,JxH~W
7.94 f 0.03
166.6 f 18.83
8.12 f 0.04
126.8 f 19.36
Urine
pH
F&c, 96
F&I, 96
28.2 f 1.64
61.6 A 7.41
1.3 + 0.47
24.6 f 1.68
92.6 f 12.62
0.8 + 0.28
meq/lijer
P
C
62.3 f 7.68
Trill Valuea zFyn
23.6 f 1.36
132.6 f 10.71
CO.06
NS
NS
CO.06
CO.06
CO.06
44.0 A 6.92
3.7 2 0.84
27.3 f 0.98
20.7 + 0.72
61.4 f 10.63
40.7 f 10.08
7.77 f 0.03
71.9 + 6.70
38.8 + 6.49
48.3 & 6.21
79.3 f 9.82
co.02
are meana * SE of two or three clearance pkr liter GFR; m, fraction&l excretion . * Infu8ed in nine animala.
26.8 f 0.71
20.7 f 1.61
periods. Abbreviations: GFR, glomendar filtration rate; V, urine flow; U-B, urine-to-blood gradient; of potassium; F&, fractional excmtion of chloride; C, control; RA, respiratory alkaloeie. P valuea r&r
103.0 f 4.61 T-HCOJGFR, to compardn
2.4 f 1.01 bicarbonate to the pvioue
Downloaded from www.physiology.org/journal/ajprenal by ${individualUser.givenNames} ${individualUser.surname} (128.143.007.175) on November 16, 2018. Copyright © 1978 the American Physiological Society. All rights reserved.
H+ SECRETION
AND
ACUTE
RESPIRATORY
F205
ALKALOSIS
60s x FIG. 1. U-B Pcop (A), urine HCO, concentration (B), and urine pH (C) during control, acute respiratory alkalosis, and acute respiratory alkalosis + Tris infusion. Points of Group IA are shown.
E
-
so-
E
$bO-
s &
30-
I
’
1
C
RA
I
I
RA+TRIS
-
C
RA
RA+TRIS
C
RA
RA+TRIS
ARA resulted in a significant decrease in U-B Pco, and urine PO, concentration. Infusion of neutral PO, resulted in an increase in U-B Pco2 and urine PO, to control levels. DISCUSSION
60
80
loo
I20
URINE
I40
HCO,
I60
180
200
220
240
260
200
(mEq/J)
FIG. 2. Interrelationship of urine pH, urine HC03 concentration, and urine Pco2. Points of Groups IA and IB are plotted. For any given urine HCO, concentration, urine. pH was higher (i.e., urine PCO, was lower) in respiratory alkalosis than in controls.
the decline in U-B Pco2 seen during ARA cannot be attributed to the decrease in urine HCO, concentration. Table 2 shows the effect of Tris administration on normal dogs with highly alkaline urine. Tris administration resulted in a significant increase in U-B Pco2, a decrease in urine pH, and an unchanged urine HCO, concentration. Urine flow, FEK, and FEN, also increased significantly. Induction of ARA during Tris administration resulted in a small decrease in U-B PC%; urine pH increased slightly but the increase did not achieve statistical significance. GFR and TmaxHCOJ GFR decreased significantly during ARA. FEN, and FEK increased significantly during ARA. Table 3 shows the results obtained during neutral PO, infusion in animals with ARA. During control periods U-B Pcoz was high despite the fact that the urine pH was only 6.39. This high U-B Pco2 is probably due to the high urine* PO, concentration. Induction of
ARA is well known to result in depression of HCOs reabsorption in the proximal tubule and to increase excretion of NaHC03 and K in the final urine (4, 16, 17). The effect of ARA on collecting duct H+ secretion has been difficult tc evaluate, since the increased delivery of HCO, to the collecting duct results in decreased net acid excretion. Chronic respiratory alkalosis is associated with a decrease in NH, excretion which is thought to be secondary to inhibition of distal nephron H+ secretion (7). Giammarco et al. (8) have demonstrated that ARA leads to a decrease in U-B Pcoz during alkalinization of the urine. They interpreted these data as indicating inhibition of H+ secretion in the collecting duct during ARA. It should be pointed out that this conclusion was based solely on the fact that ARA led to a decrease in U-B Pcoz; no other parameter of H+ secretion in the collecting duct was evaluated. We have recently demonstrated that in highly alkaline urine Pco2 is largely determined by urinary concentration and not by urinary acidification. It was necessary, therefore, to determine to what extent the decrease in U-B Pco2 seen in respiratory alkalosis was due to a reduction in urine HCO, concentration rather than to an acidification defect (2, 19). Our data confirm the observation of Giammarco et al. (8) that ARA leads to a consistent decline in urinary Pco2. Our data also demonstrate that ARA causes a decrease in urinary HCO, concentration and an increase in urine pH. Theoretically the decrease in urinary HCO, concentration could be the primary event and thereby lead to a decrease in urinary Pco~, or conversely, the decrease in urinary PCO, could be the primary event and result in a decrease in HCO, concentration due to a shifi to the right in the equilibrium in the following reaction
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SEHY, ROSEMAN, ARRUDA, AND KURTZMAN
F206 TABLE
2. Effect of Tris on U-B PCO~ before and during GFR, ml/min
Plasma pco,, -Hg
v, ml/min
acute respiratory
urine Pcq, mmHg
Urine
alkalosis pH
Urine HCOs, meq/liter
FEK,
%
?*
Gmup II (n = 6) c
69.6 f 3.67
1.2 f 0.36
29.9 f 1.16
40.0 f 1.43
P
NS
eO.06
NS
NS
67.2 f 6.36
2.8 + 0.64
32.7 f 1.46
37.6 -e 0.86
CO.06
NS
eo.01
