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Structural adaptation of intercalated cells in rat renal cortex to acute metabolic acidosis and alkalosis.

The structural responses of cells in the distal convoluted, connecting, and collecting tubule to acute acid/base changes were investigated by electron microscopy. Acute metabolic acidosis was induced by administration of ammonium chloride, and acute metabolic alkalosis by potassium or sodium bicarbonate. Morphometric analyses were performed on micrographs of randomly selected distal nephron cells. No structural responses were found in distal convoluted tubule cells, connecting tubule cells, or principal cells but prominent changes were observed in intercalated cells (I cells). Thus, the surface density of the luminal membrane in I cells was significantly higher in acidotic animals and lower in KHCO3 alkalotic animals than in controls. On the contrary, the surface density of the membrane that bounds apical vesicles was higher in KHCO3 alkalotic and lower in acidotic animals than in controls. These results suggest that the luminal membrane is internalized during alkalosis and that the membrane that bounds apical vesicles is transferred to the luminal membrane during acidosis. Since a proton translocating ATPase may be present in the luminal membrane the observations are consistent with the possibility that cortical I cells participate in the maintenance of acid/base homeostasis.

Acidosis↗

Effects of respiratory alkalosis on coronary vascular dynamics and myocardial energetics in patients with coronary artery disease.

To determine if respiratory alkalosis produces hemodynamically significant coronary vasoconstriction in coronary artery disease (CAD), we studied the effects of hyperventilation on coronary sinus blood flow (CSBF), myocardial O2 uptake, and lactate extraction in 13 CAD patients. No patient developed chest pain or ischemic ECG changes during hyperventilation. Hyperventilation increased pressure-rate product (myocardial O2 consumption index, MVO2) minimally did not change global CSBF, coronary vascular resistance or lactate extraction. However, hyperventilation increased global myocardial O2 uptake from 14.5 plus or minus 3.2 to 18.7 plus or minus 17.2 ml/min (p less than 0.01) principally due to increased myocardial O2 extraction (65.0 plus or minus 7.4 to 71.6 plus or minus 6.2%, p less than 0.01). The increased pressure-rate product was not sufficient to account for increased myocardial O2 uptake. We conclude that respiratory alkalosis increases myocardial O2 extraction but does not produce hemodynamically significant coronary vasoconstriction in CAD patients.

Adult↗

Chronic metabolic alkalosis, sucrose diet and dentine formation in young rats.

As acid-base status has an effect on bone formation and remodelling, chronic metabolic alkalosis was induced in 3-week-old rats for 6 and 7 weeks with 0.25 mol/1 of NaHCO3 in their drinking water to determine whether it has any effect on dentinogenesis in the molars. One group of rats was fed a high-sucrose diet and the other two a standard diet. The control groups had the same diets but drank distilled water. All the rats were injected with tetracycline to mark the onset of dentine apposition. The alkalotic effect of the NaHCO3 drinking water was confirmed by blood gas analysis at the end of the experiment. After death, tetracycline-marked dentine apposition was measured from sagittally sectioned mandibular molars. Chronic metabolic alkalosis did not affect dentine apposition in the groups with the high-sucrose diet, nor in the groups with the standard diet at 6 weeks, but reduced it significantly in first and second molars in 7 weeks at rats on the standard diet. A high-sucrose diet alone caused a greater reduction in the amount of dentine. The general growth of the rats was not affected in any of the groups.

Alkalosis↗

Propranolol blocks the hypophosphaturia of acute respiratory alkalosis in human subjects.

Respiratory alkalosis (RA) is seen in diverse clinical conditions including tissue hypoxia, malignancy, neurologic disorders, febrile states, pregnancy, and hepatic failure. Acute RA causes hypophosphaturia in rats, and this effect on renal phosphate handling is reversed by beta-adrenoreceptor antagonism. The objective of the present study was to determine the effect of acute RA on phosphate excretion in human patients in the absence and presence of beta-adrenoreceptor antagonism with propranolol. Twelve normal volunteers, 6 women and 6 men, were studied in two phases, once with placebo and once with intravenous infusion of propranolol. In both groups, 30-minute renal clearances were taken during normoventilation (NV) and during acute RA induced by voluntary hyperventilation. Acute RA produced a significant decrease in plasma phosphate (PPi) in the absence (deltaPPi = -0.16 +/- 0.03 mmol/L) and the presence (deltaPPi = -0.16 +/- 0.05 mmol/L) of propranolol. In the placebo group, fractional excretion of phosphate (FEPi) decreased from 24.1% +/- 3.4% in NV to 19.2% +/- 2.6% in RA. This was associated with a significant decrease in parathyroid hormone (PPTH), from 3.38 +/- 0.28 pmol/L in NV to 2.54 +/- 0.30 pmol/L in RA. In the propranolol group, FEPi did not change significantly, from 19.1% +/- 2.7% in NV to 18.7% +/- 3.0% in RA. This also occurred in the face of a decrease in PPTH, from 4.39 +/- 0.53 pmol/L in NV to 2.78 +/- 0.33 pmol/L in RA. Thus propranolol selectively changes the response of FEPi to acute RA while leaving the PPi and PPTH responses unaltered. This suggests that beta-adrenoreceptors play a role in the regulation of the response of renal phosphate handling during acute RA and that this role involves a direct tubular effect on phosphate reabsorption, independent of filtered load and hormonal status. We conclude that beta-adrenoreceptor antagonism blunts the hypophosphaturic effect of acute respiratory alkalosis in human subjects.

Adolescent↗

Dopamine enhances the phosphaturic effect of PTH during acute respiratory alkalosis.

The phosphaturic response to parathyroid hormone (PTH) is blunted during acute respiratory alkalosis. The objective of the present study was to determine the effect of dopamine on the blunted phosphaturic response to PTH during acute respiratory alkalosis. The phosphaturic response to PTH was determined in thyroparathyroidectomized (TPTX) normocapnic and respiratory alkalotic rats in the absence and presence of the infusion of exogenous dopamine (25 microg/kg/min) or of 3,4-dihydroxyphenylalanine (L-DOPA, 250 microg/kg/min) to increase endogenous dopamine synthesis. In normocapnic rats, PTH infusion (33 U/kg plus 1 U/kg/min) significantly increased the fractional excretion of phosphate (FE(Pi)), from 1.5%+/-0.5% to 28.4%+/-4.0%, (deltaFE(Pi) 26.9%+/-4.1%, n = 11, P<.05); in respiratory alkalotic rats, the increase was from 0.4%+/-0.1% to 11.4%+/-1.7% (deltaFE(Pi) 11.0%+/-1.8%, n = 13, P<.05). However, the phosphaturic response to PTH was attenuated in respiratory alkalotic rats (deltaFE(Pi) 26.9%+/-4.1% vs 11.0%+/-1.9%, P<.05). In normocapnic rats, in the presence of dopamine or L-DOPA infusions, PTH infusion significantly increased the FE(Pi) from 6.1%+/-2.3% to 33.4%+/-8.0% (deltaFE(Pi) 27.3%+/-7.0%, n = 5) and from 3.2%+/-0.6% to 32.5%+/-3.3% (deltaFE(Pi) 29.3%+/-3.2%, n = 7), respectively. In respiratory alkalotic rats, in the presence of dopamine infusion, PTH significantly increased the FE(Pi), from 0.6%+/-0.2% to 19.3%+/-3.3% (deltaFE(Pi) 18.7%+/-3.3%, n = 6); in the presence of L-DOPA infusion it increased from 1.0%+/-0.3% to 20.5%+/-2.8% (deltaFE(Pi) 19.5%+/-2.9%, n = 8, P<.05 as compared with PTH alone). Thus the phosphaturic effect of PTH that was attenuated in respiratory alkalotic rats was enhanced by stimulation of endogenous dopamine synthesis by the infusion of L-DOPA.

Acute Disease↗

Hypochloremic alkalosis in infants associated with soy protein formula.

Thirteen infants, 2 to 10 months of age, developed hypochloremic alkalosis (serum chloride 59 to 92 mEq/l) while taking Neo-Mull-Soy (Syntex), a soy-based formula low in chloride (measured to be 0 to 2 mEq/l) but with considerable potassium citrate. Range of symptoms included lethargy, anorexia, mild spitting up, diarrhea, hematuria, and growth failure. Urine chloride excretion was less than 3 mEq/l. Plasma renin activity or aldosterone, measured in six infants, was elevated. All responded promptly to supplemental salt. One infant receiving Neo-Mull-Soy redeveloped alkalosis when supplemental salt was discontinued. Two of nine apparently normal infants receiving Neo-Mull-Soy also had hypochloremia (85, 86 mEq/l). Three of four receiving Prosobee (Mead Johnson; Cl content 7 mEq/l) had urine chloride concentration less than 20 mEq/l. The chloride content of some infant formulas is insufficient to offset salt losses following mild stress.

Alkalosis↗

[Severe metabolic alkalosis following hypokalemia from a paraneoplastic Cushing syndrome].

Metabolic alkalosis is frequently observed in critically ill patients. Etiologies are numerous but endocrinal causes are rare. We report a case of a patient with severe respiratory insufficiency, metabolic alkalosis and hypokalemia. The evolution was fatal. Further explorations revealed an ectopic Adrenocorticotropine Hormone syndrome. The initial tumor was probably a small cell lung carcinoma.

ACTH Syndrome, Ectopic↗

[Severe metabolic alkalosis and beer drinking].

We describe a case report with moderately low plasma sodium level and predominant metabolic alkalosis. Others have reported acid-base balance disorders, although no clear pathophysiological explanation has been put forward. We hypothesize that, combine with poor protein intake, mild hyperosmolar beer leads to a water intoxication syndrome, whereas strong hyperosmolar beer intake more likely induces hypochloremic metabolic alkalosis.

Adult↗

Respiratory acidosis prolongs, while alkalosis shortens, the duration and recovery time of vecuronium in humans.

STUDY OBJECTIVE: To determine the effects of respiratory acidosis and alkalosis by mechanical ventilation on the onset, duration, and recovery times of vecuronium. DESIGN: Randomized, prospective study. SETTING: Operating rooms in the Sapporo Medical University Hospital and Kitami Red Cross Hospital. PATIENTS: 90 ASA physical status I and II patients undergoing lower abdominal surgery. INTERVENTIONS: Patients were randomly allocated to one of three groups by arterial carbon dioxide tension level (PaCO2; mmHg) after induction: hyperventilation group (PaCO2 = 25-35), normoventilation group (PaCO2 = 35-45), and hypoventilation group (PaCO2 = 45-55). Anesthesia was maintained by spinal block with inhalation of 50% to 66% nitrous oxide in oxygen and intermittent intravenous administration of fentanyl and midazolam with tracheal intubation. MEASUREMENTS AND MAIN RESULTS: After vecuronium 0.08 mg/kg was given, onset, duration, and recovery time were measured by mechanomyography (Biometer Myograph 2,000, Odense, Denmark). There were significant differences in the duration and recovery time of vecuronium among the normoventilation group (12.7 +/- 3.3 min and 11.8 +/- 2.8 min, respectively), the hyperventilation group (10.6 +/- 3.5 min and 9.2 +/- 2.7 min, respectively; p < 0.01), and the hypoventilation group (14.4 +/- 3.1 min and 15.0 +/- 3.7 min, respectively; p < 0.01) (mean SD). The closest significant correlation in this study was observed between recovery time and arterial blood pH (r = 0.57; p < 0.05). CONCLUSION: In humans, duration and recovery times of vecuronium are prolonged in respiratory acidosis and shortened in respiratory alkalosis.

Abdomen↗

Effect of furosemide-induced hypokalemic metabolic alkalosis on renal transport enzymes.

Hypokalemic metabolic alkalosis is one of the most common complications of chronic furosemide administration. In this study we examined acid-base composition and ATPase enzyme activities in medullary thick ascending limb of Henle's loop (MTAL) and collecting tubule (CCT and MCT) after seven days of chronic furosemide therapy. All of the studies were conducted in adrenal intact (AI) rats or in adrenalectomized (ADX) glucocorticoid replete rats replaced with a physiological dose of aldosterone (Aldo). Furosemide (F) was administered to each rat by mini-osmotic pump. In the AI+F group, plasma Aldo was high and obvious metabolic alkalosis occurred (HCO3- = 37 +/- 2 mEq/liter vs. 22 +/- 2 mEq/liter in controls, P < 0.005); activities of H-K-ATPase, H-ATPase, and Na-K-ATPase were increased approximately twofold in both CCT and MCT. In the ADX+F group (HCO3- = 28 +/- 2 mEq/liter, P < 0.05 from control), H-ATPase activity was normal in CCT and it was slightly increased in MCT. CCT and MCT H-K-ATPase activities were markedly increased (approximately twofold). Na-K-ATPase activity was the same as control in CCT but it was increased in MCT. In ADX+F+Vanadate (V) group which also had normal Aldo levels, acid-base changes were modest (20 +/- 2 mEq/liter, NS from control); in CCT and MCT H-K-ATPase and Na-K-ATPase activities were markedly reduced, but H-ATPase activity in MCT was increased. In all three experimental groups Na-K-ATPase activity in MTAL was reduced fivefold. Hypokalemia developed in both intact and ADX animals receiving furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis.

Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2-0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the I(h) current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes.

Alkalosis, Respiratory↗

Liver blood flow and oxygen consumption during metabolic acidosis and alkalosis in the greyhound.

1. Hepatic arterial and portal venous blood flow and hepatic oxygen consumption were measured in two groups of greyhounds anaesthetized with pentobarbitone. Flows were measured with electromagnetic flowmeters. 2. In the first group the effects of metabolic acidosis produced by the infusion of a molar solution of lactic acid were studied. In the second group the effects of metabolic alkalosis produced by the infusion of a molar solution of sodium bicarbonate were studied. 3. In the acidotic group hepatic arterial blood flow decreased from 35.2 to 9.6 ml min-1 100 g-1 of liver whereas portal venous blood flow increased from 94.2 to 126.1 ml min-1 100g-1 of liver. Total liver blood flow was unchanged. Hepatic oxygen consumption increased, but not significantly, while hepatic venous oxygen content decreased significantly. Hepatic arterial resistance increased from 1.18 to 2.77 mmHg min-1 ml-1 while peripheral resistance was virtually unchanged. Portal venous pressure increased from 7.08 to 11.6 mmHg. 4. In the alkalotic group portal venous blood flow increased from 112 to 137 ml min-1 100 g-1 of liver. Hepatic arterial blood flow increased, but not significantly. Total liver blood flow increased from 151 to 185 ml min-1 100 mg-1 of liver. There were no significant changes in hepatic oxygen consumption. 5. It is concluded that metabolic acidosis reduces the supply of oxygen to the liver owing to the reduction in hepatic arterial blood flow and is therefore potentially harmful, whereas metabolic alkalosis probably has no biologically significant effect on liver blood flow.

Acidosis↗

Effect of induced metabolic alkalosis on sweat composition in men.

To determine whether induced metabolic alkalosis affects sweat composition, 10 males cycled for 90 min at 62.5 +/- 1.3% peak oxygen uptake, on two separate occasions. Subjects ingested either empty capsules (placebo) or capsules containing NaHCO3- (0.3 g kg-1 body mass; six equal doses) over a 2-h period, which commenced 3 h prior to exercise. Arterialized-venous blood samples were drawn prior to and after 15, 30, 60 and 90 min of exercise. Sweat was aspirated at the end of exercise from a patch located on the right scapula region. NaHCO3- ingestion elevated blood pH, [HCO3-] and serum [Na+], whereas serum [Cl-] and [K+] were reduced, both at rest and during exercise (P < 0.05). Sweat pH was greater in the NaHCO3- trial (6.24 +/- 0.18 vs. 6.38 +/- 0.18; P < 0.05), whereas sweat [Na+] (49.5 +/- 4.8 vs. 50.2 +/- 4.3 mEq L-1), [Cl-] (37.5 +/- 5.1 vs. 39.3 +/- 4.2 mEq L-1) and [K+] (4.66 +/- 0.19 vs. 4.64 +/- 0.34 mEq L-1) did not differ between trials (P > 0.05). Sweat [HCO3-] (2.49 +/- 0.58 vs. 3.73 +/- 1.10 mEq L-1) and [lactate] (8.92 +/- 0.79 vs. 10.51 +/- 0.32 mmol L-1) tended to be greater after NaHCO3- ingestion, although significance was not reached (P=0.07 and P=0.08, respectively). These data indicate that induced metabolic alkalosis can modify sweat composition, although it is unclear whether the secretory coil, reabsorptive duct, or both are responsible for this alteration.

Adult↗

Analysis of renal tubular electrolyte transporter genes in seven patients with hypokalemic metabolic alkalosis.

BACKGROUND: Disorders that manifest hypokalemic metabolic alkalosis, such as Bartter's syndrome and Gitelman's syndrome, are caused by the malfunction of renal tubular electrolyte transporters. Bartter's syndrome may be linked to dysfunction of Na-K-2Cl cotransporter (NKCC2), renal outer medullary K channel (ROMK), or Cl channel Kb (ClC-Kb), while Gitelman's syndrome may be linked to Na-Cl cotransporter (NCCT) dysfunction. However, previous genetic analyses in these syndromes have included many heterozygotes for each gene and there has been no further analysis of other genes. Thus, to clarify the interaction of these transporter genes, in the present study we investigated all 4 transporter genes in 7 patients with hypokalemic metabolic alkalosis. METHODS: Seven patients from 5 families (patients A-G) were collected, and a mutation analysis of the 4 renal electrolyte transporter genes was performed by direct sequencing. RESULTS: We identified 12 mutations in these 7 patients. Three mutations (del245Y in NKCC2, R1009X in NCCT, V524I in ClC-Kb) have not been reported previously. In NKCC2 gene screening, patient A was homozygous for del245Y. In ClC-Kb gene screening, L27R was detected in patients B, D, and E. V524I was detected in patient C. Both T562M and E578K were observed in patients B and E. In NCCT gene screening, patients B-G shared a common novel mutation, R1009X, and patients D, E, F, and G carried this mutation in both alleles. Patients B and C carried R1009X in one allele, and a 6-amino acid insertion in exon 6 and L849H in another allele, respectively. The 4 other mutations did not result in any amino acid exchange. Despite the NCCT gene mutation, patients C and E showed normomagnesemia. CONCLUSION: Our findings demonstrate that in Bartter's and Gitelman's syndromes, it may not be uncommon to see mutations in several causative transporter genes.

Alkalosis↗

Long-term combined treatment with thiazide and potassium citrate in nephrolithiasis does not lead to hypokalemia or hypochloremic metabolic alkalosis.

BACKGROUND: Potassium citrate is commonly used in combination with a thiazide diuretic in the medical management of recurrent hypercalciuric nephrolithiasis. However, concerns have been raised that administration of this nonchloride potassium alkali with a kaliuretic and natriuretic agent such as thiazide may not be efficacious in correcting or preventing hypokalemia, and may produce hypochloremic metabolic alkalosis. This retrospective analysis was conducted to determine if these two potential complications are encountered in patients on long-term potassium citrate and thiazide therapy. METHODS: Data were collected on 95 patients who had been on combination therapy for at least 4 months from the stone clinics of the University of Texas Southwestern Medical Center, Duke University Medical Center, and Ochsner Clinic. RESULTS: Mean serum potassium concentration remained within normal limits without a significant decrease during combined therapy. Serum chloride was significantly lower from pretreatment but by only 1 mEq/L and remained within normal limits throughout treatment. There was a small increase in serum bicarbonate concentration compared to the baseline level of less than 1 mEq/L at 8 to 12 and 18 to 24 months, but not at other treatment periods. CONCLUSION: Co-administration of potassium citrate did not induce hypokalemia or hypochloremic metabolic alkalosis in our thiazide-treated patient population.

Adolescent↗

Metabolic alkalosis after orthotopic liver transplantation.

To ascertain the etiology of metabolic alkalosis (MA) following orthotopic liver transplantation (OLT) the records of patients with 123 consecutive OLTs from 1995 to 2000 were reviewed. Metabolic alkalosis occurred in 51.2% of patients. Patients with MA had a larger fluid deficit (-3991 +/- 4324 vs. -1018 +/- 4863, p < 0.05), cumulative furosemide dose (406 +/- 356 vs. 243 +/- 189, p < 0.02), and citrate load from blood transfusions (9164 +/- 4870 vs. 7809 +/- 3967, p < 0.05). There was no difference in serum lactate concentration (3.15 +/- 1.63 vs. 3.11 +/- 1.91) in patients with and without MA. The duration of ICU stay was longer in patients with MA (14.9 +/- 15.3 vs. 5.3 +/- 3.9 days, p < 0.004). Treatment of severe MA in 19 (15.4%) patients consisted of 0.1 N hydrochloric acid and/or acetazolamide. Hypokalemia and hypomagnesemia occurred in 37.4% and 59.3% of patients, respectively. In conclusion, MA is a common post-OLT complication that is associated with a longer ICU stay. Diuretic-induced volume depletion, the citrate load from blood transfusions, hypokalemia, and hypomagnesemia contribute to the pathogenesis of MA in OLT.

Alkalosis↗

[Turkish infant with hypoelectrolytemia and metabolic alkalosis as the sole manifestations of a mild form of cystic fibrosis (mutation D110H)].

We report the history of an infant who presented with hypotonic dehydration and metabolic alkalosis, in whom the diagnosis of cystic fibrosis was made on the basis of investigations for rare cystic fibrosis mutations. Since no other signs and symptoms of the CF disease were present, the finding of the rare mutation D110H on exon 4 of the CFTR-gene was paramount in the delineation of his underlying illness. He is now thriving well with a daily oral substitution of 1-2 grams of sodium chloride. A mild variant of cystic fibrosis has to be considered in infants presenting with unexplained hypoelectrolytemia and metabolic alkalosis. Like in our child, typical signs and symptoms of cystic fibrosis like maldigestion may not be present. The search has to be extended into "mild" mutations of the disease like D110H which was found in our case.

Alkalosis↗

Chronic respiratory alkalosis. The effect of sustained hyperventilation on renal regulation of acid-base equilibrium.

BACKGROUND: In normal subjects, chronic hyperventilation lowers plasma bicarbonate concentration, primarily by inhibiting the urinary excretion of net acid. The quantitative relation between reduced arterial carbon dioxide tension (PaCO2) and the plasma bicarbonate concentration in the chronic steady state has not been studied in humans, however, and the laboratory criteria for the diagnosis of chronic respiratory alkalosis therefore remain undefined. We wished to provide such reference data for clinical use. Moreover, because chronic hyperventilation paradoxically lowers blood pH still further in dogs with metabolic acidosis, we desired to study the effect of chronic hypocapnia on the plasma bicarbonate concentration (and blood pH) in normal human subjects in whom acidosis had been induced with ammonium chloride. METHODS: Under metabolic-balance conditions, we used altitude-induced hypobaric hypoxia to produce chronic hypocapnia in nine normal young men, five of whom received ammonium chloride daily to cause metabolic acidosis (the mean [+/- SE] steady-state plasma bicarbonate level in these five was 12.0 +/- 0.5 mmol per liter). RESULTS: For each decrease of 1 mm Hg (0.13 kPa) in the PaCO2, the plasma bicarbonate concentration decreased by 0.41 mmol per liter in the subjects who started with a normal plasma bicarbonate concentration and by 0.42 mmol per liter in the subjects with acidosis. In contrast to the findings in previous studies of dogs, hypocapnia increased blood pH similarly in both groups; the blood hydrogen ion concentration decreased by about 0.4 nmol per liter for every decrease of 1 mm Hg (0.13 kPa) in PaCO2. CONCLUSIONS: These results provide reference data for the diagnosis of chronic respiratory alkalosis in humans. Although chronic hypocapnia decreased plasma bicarbonate levels similarly in normal subjects with acidosis and without acidosis, the percent reduction in PaCO2 was always greater than the corresponding percent reduction in the plasma bicarbonate concentration. Therefore, as was not true of the response in dogs, the subjects' blood pH always increased with hyperventilation, regardless of the initial plasma bicarbonate concentration.

Acid-Base Equilibrium↗