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PubMed2001

The effect of dietary chloride and bicarbonate on blood pH, haematological variables, pulmonary hypertension and ascites in broiler chickens.

1. The effect of supplementing grower diets with bicarbonate or chloride on haematological variables, pulmonary hypertension syndrome and ascites in broilers exposed to cold temperature was investigated. 2. High concentrations of dietary chloride had no effect on the pH of the venous blood but a low chloride/high bicarbonate diet significantly increased blood pH. There was no consistent effect of dietary chloride or bicarbonate concentrations on growth performance, although in 1 experiment birds given a low chloride/high bicarbonate diet consumed less food and gained less weight than controls. 3. Birds fed on high-chloride diets tended to have a higher incidence of ascites and pulmonary hypertension than controls. Birds fed on low-chloride and high-bicarbonate diets had significantly lower pulmonary hypertension and lower heart weights, which may have indicated a decrease in pulmonary and systemic blood pressure. 4. We conclude that increasing dietary bicarbonate and reducing dietary chloride has potential as a low cost and effective method to reduce the pulmonary hypertension which leads to ascites in broiler chickens.

Animals↗
PubMed1959

Participation of bicarbonate in RNA and protein synthesis as indicated by virus propagation in human cells.

The propagation of a strain of Coxsackie virus, group B type 1, in human cell cultures depleted of bicarbonate has been studied. Under the described experimental conditions, bicarbonate depletion suppresses the propagation of this virus. This suppressive effect may be reversed by the addition of the following compounds to the bicarbonate-depleted cultures: (a) bicarbonate; (b) adenosine, guanosine, cytidine, and uridine; (c) adenylic, guanylic, cytidylic, and uridylic acids; (d) enzymatically degraded RNA prepared from yeasts or human embryo, or (e) RNA. The following compounds are unable to reverse the suppressive effect of bicarbonate depletion: (a) adenine, guanine, cytosine, and uracil, with or without ribose; (b) adenine, guanine, cytosine, and thymine; (c) deoxyadenosine, deoxyguanosine, deoxycytidine, and thymidine; (d) deoxyadenylic, deoxyguanylic, deoxycytidylic, and thymidylic acids; (e) enzymatically degraded DNA, or (f) DNA. The same general results as with the Coxsackie virus have been obtained with a strain of poliovirus and vaccinia virus. The failure of bicarbonate depletion to suppress completely the propagation of the poliovirus under the described condition constitutes a major difference. The significance of these findings is discussed.

Adenine↗
PubMed1997

In vitro biocompatibility evaluation of a novel bicarbonate-buffered amino-acid solution for peritoneal dialysis.

BACKGROUND: Conventional lactate-buffered peritoneal dialysis fluids containing glucose as the osmotic agent have been shown to compromise important peritoneal host defence functions. The current study employed an in vitro model using activated peripheral blood mononuclear leukocytes (PBMC) for the preclinical biocompatibility assessment of a novel bicarbonate-buffered peritoneal dialysis fluid containing 1.0% amino acids as the osmotic agent. METHODS: PBMC (5 x 10(6)/ml) were pre-exposed (10-30 mm, 37 degrees C) to bicarbonate-buffered 1% amino-acid solution, bicarbonate- or lactate-buffered 1.5% glucose fluid, or control medium (RPMI). The cells were then washed and stimulated for 2 h at 37 degrees C in RPMI containing 100 ng/ml E.coli endotoxin from strain O55:B5. The cytokines IL-6 and TNF alpha in cell supernatants were assessed using specific enzyme immunoassays, cytokine mRNA expression by reverse transcription polymerase chain reaction. RESULTS: Short, i.e. 10 min, exposure to conventional, lactate-buffered glucose fluid resulted in a significant and time-dependent inhibition of cytokine release and mRNA expression by activated PBMC, whereas the cytokine response was improved even following prolonged (up to 2 h) exposure to bicarbonate-buffered 1% amino-acid solution or bicarbonate-buffered 1.5% glucose fluid. CONCLUSIONS: Our results suggest that very short, i.e. potentially clinically relevant, exposure to conventional dialysis fluid impairs the cytokine response by activated leukocytes. In this respect, the use of bicarbonate-buffered solutions containing 1.0% amino acids or 1.5% glucose may result in improved biocompatibility properties.

Amino Acids↗
PubMed1998

A controlled trial of two bicarbonate-containing dialysis fluids for CAPD--final report.

BACKGROUND: The combination of a low pH and a high concentration of lactate which is present in most dialysis fluids is found to be cytotoxic in vitro. For these reasons it would seem logical to use a bicarbonate-containing solution and thus automatically provide a solution with a neutral pH. METHODS: A parallel, randomized, open-label, prospective 2-month trial with an optional 4 month extension was undertaken to compare two novel bicarbonate-based solutions; one containing 38 mmol/l of bicarbonate (B), and one containing a mixture of 25 mmol/l bicarbonate and 15 mmol/l of lactate (B/L), with a control solution (C) containing 40 mmol/l lactate. RESULTS: Three groups of 19 (C), 20 (B), and 20 (B/L) patients were recruited and data from approximately 55 patient months were accumulated in each group. The data show that both bicarbonate-based solutions maintain acid-base levels within the normal range, that there were no changes in any of the other blood biochemistry parameters measured in the peritoneal equilibration test or with regard to adequacy of dialysis, and that furthermore, both solutions were well tolerated. CONCLUSIONS: This study showed that either the bicarbonate or bicarbonate/lactate solutions could be utilized efficaciously in patients undergoing CAPD.

Acid-Base Equilibrium↗
PubMed1998

Automated peritoneal dialysis with 'on-line'-prepared bicarbonate-buffered dialysate: technique and first clinical experiences.

BACKGROUND: Automated peritoneal dialysis (APD) has the possibility of increasing the dialysis efficacy by using higher fill volumes, frequent dialysate exchanges, and tidal techniques. It is then possible to treat patients adequately without residual renal function. The drawbacks of the required high amounts of dialysis solution of up to 30 litres per session are the high costs of lactate-based dialysate bags and difficulties for the patients in handling these bags. So far, bicarbonate-based peritoneal dialysate, which may be more biocompatible, is only available for CAPD in double-chamber bags. In APD this could be overcome by 'on-line' preparation of bicarbonate-buffered dialysate using advanced technologies originally designed for on-line preparation of substitution fluid for haemofiltration. METHODS: Four patients without residual renal function were treated with APD five times weekly in a crossover study design. Patients received standard lactate-based (35 mmol/l) treatment (25 litres per session each) in weeks 1 and 3. In week 2 on-line-produced bicarbonate-buffered (37 mmol/l) dialysate was used. This dialysate was prepared by an AK 100 Ultra haemodialysis machine. The machine was modified for adding glucose from a 50% concentrate to the desired concentration of 1.7%. Electrolytes, pH, pCO2, and dialysis efficacy parameters were measured. Microbiological testing was carefully performed. RESULTS: Creatinine clearances, Kt/V, and pCO2 did not vary between the different treatment phases, whereas the pH showed a distinct increase during the bicarbonate phase. Repeated determinations of endotoxins and culturing showed no contamination of the dialysate. The composition of the produced dialysate was reproducible with respect to pH, pCO2, sodium, calcium and bicarbonate, whereas the glucose concentration varied by +/- 20%. CONCLUSIONS: On-line preparation of PD fluid with the AK 100 Ultra is easy and safe to handle. APD with dialysate containing 37 mmol/l bicarbonate provides improved acid base balance and possibly improved biocompatibility, and may lead to a significant cost reduction. Further development in order to provide smaller machines and more precise ways of achieving a desired dialysate glucose concentration is necessary.

Adult↗
PubMed2001

Venous serum chloride and bicarbonate measurements in the evaluation of respiratory function in motor neuron disease.

Respiratory failure, with or without pneumonia, is the usual cause of death in patients with motor neuron disease (MND). Forced vital capacity (FVC) is often used to monitor respiratory function in MND and is, in part, predictive of survival time. However, such volitional tests are unreliable in many patients, especially later in the disease, and access to hospital laboratories can also be a problem for some disabled patients. We assessed the use of domiciliary venous serum chloride and bicarbonate measurements in evaluating respiratory function in MND. Newly-diagnosed MND patients (n=23) were followed-up at home every 3 months for up to 15 months. Respiratory symptoms were measured using a questionnaire, and FVC was documented. Venous serum chloride and bicarbonate were also measured. One patient had symptoms of airway obstruction disease, and was excluded from the analysis. Ten patients developed abnormally low chloride (mean 95, range 88-97, reference interval 98-107 mmol/l) and an abnormally high bicarbonate (mean 33, range 31-37, reference interval 22-30 mmol/l) during follow-up, of whom eight died within the next 5 (mean 2.2, range 0.5-5) months; two were still alive at the end of the study but had developed respiratory symptoms. Twelve patients had normal chloride and bicarbonate during follow-up: all were still alive at 15 months, all had a FVC of >50% predicted, and only one had respiratory symptoms at their last assessment. Raised bicarbonate and low chloride were associated with the presence of respiratory symptoms suggesting respiratory muscle weakness. Venous serum chloride and bicarbonate potentially can provide useful information about respiratory status and prognosis in MND patients.

Aged↗
PubMed1998

Adding sodium bicarbonate to lidocaine enhances the depth of epidural blockade.

UNLABELLED: It is controversial whether adding CO2 or sodium bicarbonate to local anesthetics enhances the depth of epidural blockade. Repeated electrical stimulation is a reliable test for assessing epidural analgesia and evokes temporal summation. We used this test to investigate the analgesic effect of lidocaine, with or without CO2 or bicarbonate. Twenty-four patients undergoing epidural blockade with 20 mL lidocaine 2% at L2-3 were randomly divided into three groups: lidocaine hydrochloride, lidocaine CO2, and lidocaine plus 2 mL sodium bicarbonate 8.4%. Pain threshold after repeated electrical stimulation (five impulses at 2 Hz), pinprick, and cold test were performed at S1 and L4. Motor block was assessed. The addition of bicarbonate resulted in higher pain thresholds (P < 0.0001), faster onset of action (P = 0.009), and higher degree of motor block (P = 0.004) compared with lidocaine hydrochloride. We found no significant differences between lidocaine CO2 and hydrochloride. Most of these results were not confirmed by pinprick and cold tests. We conclude that the addition of sodium bicarbonate to lidocaine enhances the depth of epidural blockade, increases inhibition of temporal summation, and hastens the onset of block. Pinprick and cold are inadequate tests for comparing drugs for epidural anesthesia. IMPLICATIONS: We measured pain perception during epidural anesthesia by delivering electrical stimuli to the knee and foot. We found that the addition of sodium bicarbonate to the local anesthetic lidocaine enhances analgesia. We observed no effect of adding carbon dioxide to lidocaine.

Adult↗
PubMed1990

Effects of aging on duodenal bicarbonate secretion.

The incidence of duodenal ulcer increases with age, but acid secretion does not. We have investigated the effects of aging on a mechanism of duodenal mucosal defense. Basal and acid-stimulated bicarbonate secretions were measured in the proximal duodenum in anesthetized rats of three different age groups (3 months, 1 year, and 2 years). The proximal duodenum was cannulated in situ between two plastic tubes that extend downward from a titrating chamber, and bicarbonate secretion was measured by the method of Flemström et al. Although there was no significant difference in basal secretion among three groups, bicarbonate secretion in response to luminal acid (100 mmol/L [millimolar] HCl) was diminished in 1-year-old and 2-year-old rats (1-hour integrated bicarbonate secretions; 3 months = 5.8 +/- 0.7; 1 year = 3.1 +/- 1.0*; 2 years = 2.0 +/- 0.7*). We also studied the effects of two mediators for acid-stimulated duodenal bicarbonate secretion, vasoactive intestinal polypeptide (VIP), and prostaglandin E2 (PGE2). Intravenous infusion of VIP (0.4, 4, 40 nmol/kg/hr) and intraluminal administration of PGE2 (10(-5) mol/L [molar] and 10(-4) mol/L) induced duodenal bicarbonate secretion in a dose-dependent manner in all three groups, without significant difference between groups. These findings suggest that the release of mediator(s) in response to acid is decreased in the duodenum of the aging rats. The progressive breakdown in mucosal defense mechanisms with increasing age may explain, at least in part, the age-related increase of incidence of duodenal ulcer disease.

Acid-Base Equilibrium↗
PubMedDate not supplied

A new sterile bicarbonate dialysis solution for use during cardiopulmonary bypass.

Adding a dialysis filter to the perfusion circuit at the end of cardiopulmonary bypass (CPB) has become an accepted means of reducing potassium rapidly and safely. Rapid removal of solute requires a dialysate for diffusion, and peritoneal dialysis solutions have been the standard because of availability, although occasionally normal saline or bicarb/ saline mixtures are used. Cardioplegia solution is high in glucose as well as potassium and, with many diabetic patients undergoing CPB, it is desirable to minimize glucose loads. In this prospective cohort study, six patients received a commercially available sterile bicarbonate dialysate prepared in a point of care fashion. From the cardiovascular data base, four control patients (receiving lactate based dialysis solution during CPB) were matched for age, surgery type, body surface area (BSA), and pump duration for each of the six patients receiving bicarbonate dialysate. All of the control patients were dialysed against lactate buffered peritoneal dialysis solution. Plasma levels of potassium, glucose, and bicarb were measured before and after dialysis for each dialysate. Plasma potassium, glucose, and bicarb were not significantly different at start of dialysis. The lactate dialysate (LD) group received a mean of 17.4+/-7.7 L of lactate containing dialysate versus 14.6+/-4.7 L of bicarbonate dialysate (BD) (p = 0.41). After dialysis, potassium had been reduced to a similar degree in both groups, but plasma glucose levels had increased during LD while they fell during BD, and bicarbonate levels fell during LD while they rose during BD. Use of a commercially available sterile bicarbonate dialysate can safely help to lower plasma potassium during CPB and preserve more physiologic levels of glucose and bicarbonate.

Acidosis↗
PubMed1994

Effects of THAM and sodium bicarbonate on intracranial pressure and mean arterial pressure in an animal model of focal cerebral injury.

Episodes of arterial hypotension are associated with an increased mortality in head injury patients. Rapid infusion of sodium bicarbonate in such patients may cause hypotension and elevate intracranial pressure. Therefore, we examined the effects of tromethamine (THAM) versus bicarbonate on intracranial pressure and blood pressure in a model of focal cerebral injury. THAM is a buffer that in previous studies has been shown to lower intracranial pressure. After creation of a cryogenic lesion in 13 New Zealand white rabbits, equivalent infusions (15 s duration) of sodium bicarbonate and THAM (2 mEq/kg) were administered sequentially to each animal in random order. Rapid infusion was chosen to simulate the administration of these drugs during a resuscitation. THAM infusion was associated with a significantly lower intracranial pressure and blood pressure than bicarbonate. The fall in blood pressure was great enough that cerebral perfusion pressure after THAM infusion was significantly lower than after bicarbonate infusion. In this model of cerebral injury, rapid infusion of THAM offered no therapeutic advantage over bicarbonate.

Animals↗
PubMed2006

Apparent bicarbonate space in children.

The amount needed to change the concentration of a solute requires the knowledge of its volume of distribution in the solution. Electrolytes that do not participate in active metabolic reactions have a fixed volume of distribution that corresponds to the volume of water in which they solubilize. Bicarbonate infusion is used to correct hyperchloremic metabolic acidosis. Its volume of distribution (bicarbonate space) changes with its participation in the blood buffer systems. In other words, it is not a fixed physical volume, like that of other solutes. In this paper, we shall review experimental studies that supported evidence for this knowledge and analyze the basic hypothesis to explain the phenomena. Since we have not found clinical studies in children, we shall report our experience in a group of patients with metabolic acidosis treated with bicarbonate infusion in whom apparent bicarbonate space was measured and compared with data in adults from the literature. Guidelines for amount of bicarbonate needed to increase its concentration according to baseline bicarbonate concentration will be suggested.

Acidosis↗
PubMed1996

Metabolic acidosis in hemodialysis patients: a study of prevalence and factors affecting intradialytic bicarbonate gain.

The correction of uremic acidosis is one of the goals of hemodialysis; however, despite acceptable hemodialysis protocols, metabolic acidosis remains a common problem. The prevalence of acidosis and significance of factors affecting bicarbonate flux during hemodialysis were studied. A cohort of 70 stable patients receiving high-efficiency hemodialysis for at least 4 months was studied prospectively over a 1-year period. Twenty patients (28%) had a mean predialysis serum bicarbonate of less than 21 mEq/L. The patients with or without metabolic acidosis had similar mean net ultrafiltration and percent ultrafiltration, but acidotic patients had a higher percent increase in bicarbonate during hemodialysis (35 +/- 12 versus 27 +/- 10 [p = 0.008]). The latter suggests an increased net daily acid gain in patients with metabolic acidosis (1.19 +/- 0.32 mEq/kg versus 1.05 +/- 0.35 mEq/kg [p = 0.04]). A review of factors affecting intradialytic bicarbonate gain showed that predialysis serum bicarbonate (diffusive gradient) was the most significant with a demonstrated linear relationship between these two variables (R2 0.51). The role of dialysance and blood flow, assessed together using percent urea reduction, was minor as was the effect of ultrafiltration. At our level of dialysis delivery, prevalence of metabolic acidosis is low, and dialysis-related factors do not contribute to the persistence of metabolic acidosis. Net daily acid gain was higher in acidotic patients and accounts for the long-term maintenance of metabolic acidosis. For individual dialysis treatments, the diffusive gradient is the most important determinant of bicarbonate gain, with only a minor role being demonstrated for percent urea reduction and ultrafiltration rate.

Acidosis, Renal Tubular↗
PubMed1983

Evidence for bicarbonate-dependent magnesium reabsorption.

During ethacrynic acid administration about 50% of the filtered load of magnesium is reabsorbed. To examine whether the remaining component of magnesium reabsorption is bicarbonate-dependent, i.e. varies with factors known to alter passive reabsorption, experiments were performed in anesthetized dogs. During ethacrynic acid administration MgCl2 infusion raised the plasma concentration of magnesium (PMg) from 0.64 +/- 0.05 to 3.06 +/- 0.27 mM and doubled magnesium reabsorption. The infusion of acetazolamide at high PMg reduced bicarbonate reabsorption by 41 +/- 3% and magnesium reabsorption by 31 +/- 16%. When plasma pH was reduced to 7.04 +/- 0.02 and increased to 7.83 +/- 0.02 by altering PCO2 at a constant plasma bicarbonate concentration of 31.2 +/- 0.8 mM, magnesium and bicarbonate reabsorption were correlated (r = 0.82). The infusion of mannitol, which acts by reducing passive solute transport without affecting bicarbonate reabsorption, halved magnesium reabsorption. By combining mannitol and acetazolamide infusions, only 6 +/- 4% of the filtered magnesium was still reabsorbed. These results indicate that the reabsorption of magnesium remaining after the infusion of ethacrynic acid and after raising PMg varies with changes in PCO2 and is inhibited by the infusion of acetazolamide and mannitol as expected for bicarbonate-dependent passive reabsorption.

Acetazolamide↗
PubMed1987

How bicarbonate loading inhibits tubular reabsorption of NaCl in dog kidneys.

During continuous infusion of ethacrynic acid in dogs, changes in glomerular filtration rate (GFR) and PCO2 at constant plasma bicarbonate concentration (PHCO3) alter bicarbonate and chloride reabsorption in a ratio of 1:2. This ratio did not apply when PHCO3 was raised by bicarbonate loading in 11 anaesthetized volume-expanded dogs. A rise in PHCO3 from 30 to 54 mM at constant PCO2 and GFR reduced sodium reabsorption during ethacrynic acid infusion from 3586 +/- 725 to 2449 +/- 403 mumol min-1. Bicarbonate and chloride reabsorption were reduced in a ratio of 1:10. When plasma pH was restored from 7.8 to 7.5 by raising PCO2, the inhibitory effect on chloride reabsorption was halved. At constant plasma pH 7.5 a rise in PHCO3 from 20 to 30 mM reduced chloride reabsorption by 20%. A further 30% inhibition was caused by raising PHCO3 from 30 to 54 mM. Bicarbonate reabsorption was highest at PHCO3 54 mM, suggesting a large capacity for bicarbonate reabsorption if PHCO3 is raised at constant plasma pH 7.5. Water and NaCl reabsorption remaining during ethacrynic acid infusion is almost equally inhibited by alkalosis and by an osmotic effect of unreabsorbed NaHCO3.

Animals↗
PubMed1980

Secretion and reabsorption of bicarbonate in single renal tubules of the rabbit.

Bicarbonate is transported by a number of different renal tubule segments. Both the rates of transport and the mechanisms involved differ between the segments. Although bicarbonate is absorbed by both proximal tubules and collecting ducts, bicarbonate secretion has been observed only in the collecting ducts. Bicarbonate secretion in cortical collecting ducts, bicarbonate secretion has been observed only in the collecting ducts. Bicarbonate secretion in cortical collecting ducts results from conditioning of that tubule segment, following administration of alkali to the animals.

Absorption↗
PubMed1984

Carbonic anhydrase-dependent bicarbonate transport in the kidney.

Carbonic anhydrase is abundantly distributed in renal tissue and functions, as in other epithelia, to catalyze the hydration-dehydration reaction of CO2. The proximal tubule is responsible for at least 80% of whole kidney bicarbonate transport and is mediated by proton secretion. Membrane-bound carbonic anhydrase appears to function primarily to prevent the rapid development of limiting pH gradients in this segment, and contributes importantly to the ability of this "leaky" epithelium to transport bicarbonate at high rates. Bicarbonate transport beyond the proximal tubule occurs in the loop of Henle and the medullary collecting tubule. After complete inhibition of the enzyme, bicarbonate appears to be transported passively as a result of favorable outwardly directed bicarbonate concentration gradients that are generated in the tubule lumen of more distal segments by water abstraction. This finding explains the widely appreciated, but seemingly paradoxical, view that complete inhibition of the renal enzyme results in excretion of only 30% of the filtered bicarbonate load. Although an additional role of carbonic anhydrase in mediating NaCl transport in the cortical thick ascending limb of Henle has been proposed, further investigation regarding the significance of this process is in order.

Acetazolamide↗
PubMedDate not supplied

Effect of dietary starch, fat, and bicarbonate content on exercise responses and serum creatine kinase activity in equine recurrent exertional rhabdomyolysis.

To determine the effect of dietary starch, bicarbonate, and fat content on metabolic responses and serum creatine kinase (CK) activity in exercising Thoroughbreds with recurrent exertional rhabdomyolysis (RER), 5 RER horses were fed 3 isocaloric diets (28.8 Mcal/d [120.5 MJ/d]) for 3 weeks in a crossover design and exercised for 30 minutes on a treadmill 5 days/wk. On the last day of each diet, an incremental standardized exercise test (SET) was performed. The starch diet contained 40% digestible energy (DE) as starch and 5% as fat: the bicarbonate-starch diet was identical but was supplemented with sodium bicarbonate (4.2% of the pellet): and the fat diet provided 7% DE as starch and 20% as fat. Serum CK activity before the SET was similar among the diets. Serum CK activity (log transformed) after submaximal exercise differed dramatically among the diets and was greatest on the bicarbonate-starch diet (6.51 +/- 1.5) and lowest on the fat diet (5.71 +/- 0.6). Appreciable differences were observed in the severity of RER among individual horses. Postexercise plasma pH, bicarbonate concentration, and lactate concentration did not differ among the diets. Resting heart rates before the SET were markedly lower on the fat diet than on the starch diet. Muscle lactate and glycogen concentrations before and after the SET did not differ markedly among the diets. A high-fat, low-starch diet results in dramatically lower postexercise CK activity in severely affected RER horses than does a low-fat, high-starch diet without measurably altering muscle lactate and glycogen concentrations. Dietary bicarbonate supplementation at the concentration administered in this study did not prevent increased serum CK activity on a high-starch diet.

Animal Nutritional Physiological Phenomena↗
PubMed1970

The origin and secretion of pancreatic juice bicarbonate.

1. The rate of secretion from a saline-perfused preparation of the cat's pancreas is directly proportional to the perfusate bicarbonate concentration. When all bicarbonate is omitted, secretion completely or almost completely ceases.2. Incorporation of [(14)C]bicarbonate into the perfusion fluid results in its prompt appearance in the juice. The radioactive label is concentrated four to five times in the juice just as the total juice bicarbonate is four to five times greater than perfusate bicarbonate.3. These two observations suggest that about 95% of pancreatic juice bicarbonate is derived from perfusate (plasma) bicarbonate.4. The inhibition of pancreatic secretion from the perfused gland by acetazolamide is similar to that observed in the intact animal.5. There is a fall in pH and rise in P(CO2) in the perfusion fluid leaving the gland which is greater during secretion than at rest.6. It is therefore suggested that during secretion, hydrogen ions pass from the gland into the perfusate (plasma), thus increasing the production of carbon dioxide from circulating bicarbonate. This carbon dioxide diffuses into the cell, is rehydrated (partly under the influence of carbonic anhydrase) and finally is secreted, thus establishing the necessary gradient for the continued diffusion of carbon dioxide into the cell.

Acetazolamide↗