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Sodium bicarbonate infusion test: a new method for evaluating parathyroid function.

We have developed a new test for estimating the secretory capacity of parathyroid hormone (PTH) from the parathyroid gland. Sodium bicarbonate solution [8.4% (w/v); 35 ml/m(2) body surface area] was infused for 2 min, and blood samples for the determination of plasma ionized calcium, plasma PTH (intact, midregion, carboxy-terminus) and related parameters were serially obtained. In 8 healthy volunteers, the mean (+/-SE) plasma ionized calcium fell promptly and significantly (from 1.21 +/- 0.01 to 1.11 +/- 0.01 mmol/L) after the sodium bicarbonate infusion. The mean (+/-SE) plasma intact PTH increased promptly and significantly, by more than four fold (42.3 +/- 4.2 to 182.4 +/- 34.7 pg/ml), and then gradually returned to basal levels. In patients with partial hypoparathyroidism who have detectable basal plasma levels of PTH, the absolute increment in PTH levels was much less, and in the plasma obtained from patients with complete hypoparathyroidism, absolutely no response was observed. Plasma obtained from patients diagnosed with primary hyperparathyroidism (parathyroid adenoma or hyperplasia) has high basal PTH levels. The response to the sodium bicarbonate infusion in these patients was markedly blunted (less than a two-fold increase in all cases examined). No significant adverse effects were observed during the procedure. Therefore, the sodium bicarbonate infusion test is a simple and sensitive method to stimulate PTH release, and is clinically useful for evaluating parathyroid gland function.

Adult↗

Combined creatine and sodium bicarbonate supplementation enhances interval swimming.

This study examined the effect of simultaneous supplementation of creatine and sodium bicarbonate on consecutive maximal swims. Sixteen competitive male and female swimmers completed, in a randomized order, 2 different treatments (placebo and a combination of creatine and sodium bicarbonate) with 30 days of washout period between treatments in a double-blind crossover procedure. Both treatments consisted of placebo or creatine supplementation (20 g per day) in 6 days. In the morning of the seventh day, there was placebo or sodium bicarbonate supplementation (0.3 g per kg body weight) during 2 hours before a warm-up for 2 maximal 100-m freestyle swims that were performed with a passive recovery of 10 minutes in between. The first swims were similar, but the increase in time of the second versus the first 100-m swimming time was 0.9 seconds less (p < 0.05) in the combination group than in placebo. Mean blood pH was higher (p < 0.01-0.001) in the combination group than in placebo after supplementation on the test day. Mean blood pH decreased (p < 0.05) similarly during the swims in both groups. Mean blood lactate increased (p < 0.001) during the swims, but there were no differences in peak blood lactate between the combination group (14.9 +/- 0.9 mmol.L(-1)) and placebo (13.4 +/- 1.0 mmol.L(-1)). The data indicate that simultaneous supplementation of creatine and sodium bicarbonate enhances performance in consecutive maximal swims.

Adolescent↗

Significance of post-exercise increment of urinary bicarbonate and pH in subjects loaded with submaximal cycling exercise.

We studied the changes in urinary bicarbonate, urinary pH and some physical parameters such as minute ventilation (VE), oxygen consumption (VO2), respiratory carbon dioxide (VCO2), heart rate, blood pressure, and blood lactate, before and after the submaximal exercise. Six male subjects aged 28-33 years were involved in the study. They performed the incremental exercise test using a bicycle ergometer until exhaustion. Levels of VE, VO2, VCO2, heart rate, and blood pressure increased continuously with an increase in cycling intensity. These parameters markedly decreased and reached the baseline levels within 5-10 minutes after the termination of exercise. According to an increase in cycling intensity, blood lactate increased continuously during exercise, but after termination of exercise the return of lactate to the baseline level was markedly retarded. Urinary bicarbonate and pH were within the range of those at 0 time (baseline levels) from the beginning until 30 minutes after the exercise. However, they began to increase abruptly about 30 minutes after the exercise, and continued to increase extensively for 2 hours thereafter. Such marked increase in urinary bicarbonate and pH seemed to be correlated with the aerobic metabolism of lactate in the muscles, liver, and kidney, finally producing CO2. It was also suggested that the measurement of urinary bicarbonate and pH may be useful for the estimation of physiological changes in the body after submaximal incremental cycling exercise loading.

Adult↗

Endothelin inhibits fluid and bicarbonate transport in part by reducing Na+/K+ ATPase activity in the rat proximal straight tubule.

The effects of endothelin on fluid and bicarbonate absorption and Na+/K+ ATPase activity in the proximal straight tubule were investigated. During the control period, fluid absorption was 0.59 +/- 0.03 nL/mm.min when tubules were perfused at 4.76 nL/mm.min. After treatment with 10(-9) M endothelin, fluid absorption fell to 0.36 +/- 0.06 nL/mm.min when perfused at a similar flow rate. During the control period, bicarbonate absorption was 67.9 +/- 3.6 pmol/mm.min. After treatment with endothelin, it fell to 42.8 +/- 4.3 pmol/mm.min, an inhibition of 38%. To test whether inhibition of fluid and bicarbonate absorption was due to suppression of Na+/K+ ATPase activity, the effect of endothelin on pump activity was investigated. In control tubules, Na+/K+ ATPase activity was 85 +/- 5 pmol/mm.min. In endothelin-treated tubules, Na+/K+ ATPase activity was 68 +/- 4 pmol/mm.min, a reduction of 20%. From these data, it was concluded that endothelin inhibits fluid and bicarbonate transport in the proximal tubule and that this inhibition is in part due to suppression of Na+/K+ ATPase activity.

Animals↗

A prospective study of pyrogenic reactions in hemodialysis patients using bicarbonate dialysis fluids filtered to remove bacteria and endotoxin.

Pyrogenic reactions (PR) are a well-recognized complication of hemodialysis and have been associated with dialyzer reuse, high-flux dialysis, and bicarbonate dialysate. However, the roles of bacteria and endotoxin in dialysate for producing PR are not well defined. To determine the effect of removing most bacteria and endotoxin from the dialysate on the incidence of PR, a cohort of chronic hemodialysis patients receiving high-flux, high-efficiency, or conventional hemodialysis at three centers with bicarbonate dialysis fluids that had been filtered with a polysulfone high-flux hemodialyzer was prospectively studied. Unfiltered bicarbonate concentrate had median bacterial and endotoxin concentrations of 479,000 CFU/mL and 39,800 pg/mL, respectively. After filtration of the bicarbonate concentrate at the central proportioner, dialysate had a median 9.2 CFU/mL of bacteria and 17.8 pg/mL of endotoxin. Dialysate filtered at individual proportioning dialysis machines had a median 0.001 CFU/mL of bacteria and 0.19 pg/mL of endotoxin. Nine PR were identified among 303 patients after 28,007 hemodialysis treatments (0.3 PR/1,000 treatments). The rate of PR was similar for the three hemodialysis treatment modalities and for first-use compared with reused dialyzers. Although the PR rate in this study was lower (P = 0.046) than the PR rate of a previous study with unfiltered dialysis fluids (0.7 PR/1,000 treatments), it represents a difference of only 10 PR in over 28,000 treatments. It was concluded that filtration of hemodialysis fluids is efficacious in removing bacterial and endotoxin contamination and can result in a lower incidence of PR in patients receiving high-flux, high-efficiency, or conventional hemodialysis.

Adult↗

Effect of rioprostil on the gastric acid and bicarbonate secretion in patients with gastric ulcer.

This double-blind trial is undertaken to study the effect of rioprostil on the acid and bicarbonate secretion in patients with gastric ulcer. Pentagastrin stimulation is performed before treatment and 9-20 days after the onset of treatment. In the four patients treated with rioprostil, the bicarbonate secretion increases and the parietal volume secretion decreases (p less than 0.05). The eight patients treated with ranitidine do not show an increase in bicarbonate secretion, but the decrease of the basal acid secretion is more prominent. The index of stimulated bicarbonate secretion/maximal acid output increases by 40% in those who are treated with rioprostil. This may be due to an increase in the cytoprotective activity and to a decrease in the aggressive activity of the gastric juice by rioprostil.

Adult↗

Effect of bicarbonate, acetate, and citrate on water and sodium movement in normal and cholera toxin-treated rat small intestine.

Bicarbonate, citrate, or acetate are commonly included in oral rehydration solutions to correct acidosis and possibly because of their ability to promote water and sodium absorption. We have investigated the effect of these anions on water and sodium transport in normal and also in secreting (cholera toxin-treated) rat small intestine using a single-pass perfusion technique. In normal jejunum bicarbonate and acetate produced net absorption, and citrate net secretion of both water and sodium. In normal ileum all anions produced net absorption of water and sodium. In the secreting jejunum, however, bicarbonate had no effect on water and sodium secretion, whereas acetate and citrate actually enhanced the secretory state for both water and sodium. None of these anions had any effect on water and sodium secretion in the ileum. These observations suggest that normal and secreting intestine are qualitatively different with regard to handling of these organic anions. The addition, therefore, of bicarbonate, acetate, or citrate to oral rehydration solutions may have no beneficial effect with regard to the promotion of water and sodium absorption in the secreting intestine during acute diarrhoeal states and could actually be deleterious.

Acetates↗

Gastric bicarbonate secretion, acid secretion, and mucosal blood flow during influence of pentagastrin and omeprazole in the cat.

In this study secretion of bicarbonate and acid and mucosal blood flow were determined simultaneously in cats. The gastric lumen of anesthetized cats was continuously perfused with isotonic saline. Secretion of HCO-3 and H+ was calculated from continuous measurements of pH and PCO2 in the perfusate. Mucosal blood was measured by means of radiolabeled microspheres. Under resting acid secretory conditions, bicarbonate secretion into the gastric lumen averaged 1.0 mumol/min. Somewhat surprising, both omeprazole (4 mg/kg as bolus) and pentagastrin (16 micrograms/kg.h intravenously) significantly reduced the HCO-3 secretion. Omeprazole did not influence mucosal blood flow, whereas corpus mucosal blood flow increased during pentagastrin stimulation. Under resting acid secretory conditions and during omeprazole treatment there was a close linear relationship between acid and bicarbonate secretion. No such relationship was found during pentagastrin stimulation of the mucosa. No consistent relationship was obtained between blood flow and bicarbonate secretion in normal gastric mucosa.

Animals↗

Relative importance of pancreatic, hepatic, and mucosal bicarbonate in duodenal neutralization of acid in anaesthetized pigs.

Pancreatic and hepatic bicarbonate secretion and the disappearance rate of acid during duodenal acidification were measured simultaneously in anaesthetized pigs. Perfusion of the duodenum with HCl resulted in an increase in both hepatic and pancreatic bicarbonate secretion. During all acid loads hepatic bicarbonate secretion was significantly greater than pancreatic secretion. Furthermore, the disappearance rate of acid in the duodenum during diversion of both bile and pancreatic juice was significantly greater than the amount of acid which could be neutralized by the concomitant pancreatic bicarbonate secretion. Diversion of pancreatic juice from the duodenum did not affect the disappearance rate of acid at any acid load, whereas diversion of bile caused a significant decrease. Thus, in the anaesthetized pig the liver and the duodenal mucosa are of greater importance than the pancreas for the neutralization of acid in the duodenum. It is suggested that the importance of the pancreatic contribution to duodenal neutralization should be reevaluated in other species, including man.

Animals↗

Peptic ulcer pathophysiology: acid, bicarbonate, and mucosal function.

The previously accepted role of gastric acid hypersecretion in peptic ulcer disease has been modified by studies showing no correlation between acid output and clinical outcome of ulcer disease, or between ulcer recurrence rate after vagotomy and preoperative acid secretion. At the same time, studies have been unable to demonstrate increased acidity in the duodenal bulb in patients with duodenal ulcer, and consequently more emphasis has been given to the mucosal protecting mechanisms. The existence of an active gastric and duodenal mucosal bicarbonate secretion creates a pH gradient from the luminal acid to near neutrality at the surface of the epithelial cells, thereby acting as an important mucosal defence mechanism. The regulation of bicarbonate secretion is a complex process related to motility and neural activity. Stimulation is by acid, PGE2, NO, VIP, cAMP, and mucosal protective agents. Bicarbonate secretion is inhibited by atropine, muscarinic antagonists, alpha-adrenoceptor agonists, indomethacin, bile acids, tobacco smoking, and probably also by infection by Helicobacter pylori. Apart from mucus and bicarbonate, the mucosal defence is supported by a hydrophobic epithelial lining, rapid cell removal and repair regulated by epidermal growth factor. Sufficient mucosal blood flow, including a normal acid/base balance, is important for subepithelial protection. In today's model of ulcer pathogenesis, gastric acid and H. pylori work in concert as aggressive factors, with the open question being: why does only a fraction of the infected population develop an ulcer?

Animals↗

Bicarbonate and the trans-endothelial short circuit current of human cornea.

Experiments were performed in vitro, to determine the effect of bicarbonate ion concentration on human cornea endothelial potential difference, short circuit current and resistance. Decreasing the bicarbonate concentration resulted in a reversible and parallel fall in potential differences and short circuit current, whereas resistance remained unchanged. The results demonstrate that bicarbonate is a necessary component of the mechanisms that generate trans-endothelial short circuit current. Similarities between data derived from rabbit, ox and human suggest that a common underlying bicarbonate dependent mechanism is operating in these species.

Action Potentials↗

Thermodynamical aspects of the determination of bicarbonate in urine.

Despite the fact that the composition of urine varies a lot during the day, this has essentially been neglected as a factor of importance in determinations of urine bicarbonate. The investigations reviewed in combination with an own study shows that qualitative and quantitative factors in urine composition impacts the solubility of carbon dioxide as well as the dissociation constant for the bicarbonate buffer system. These two "constants" are of outstanding importance in the determination of bicarbonate, using the total carbonic acid method as well as the carbon dioxide equilibration method. Nomograms are presented to quantify the influence of different urine compositions on the determinations of bicarbonate in final urine and tubular fluid.

Bicarbonates↗

The influence of potassium and bicarbonate on red blood cell sodium in the DOCA-hypertensive pig.

The effects of plasma potassium, and blood bicarbonate on red blood cell sodium were studied in vivo in seven pigs implanted subcutaneously with DOCA (100 mg/kg) impregnated in Silastic. Mean arterial pressure, red blood cell sodium, plasma sodium, plasma potassium, and blood bicarbonate were measured from 5 days pre-implant to 30 days post-implant. One day post-implant, the pigs had significant increases in mean arterial pressure and red cell sodium content, and a significant decrease in plasma potassium concentration. In KCl infusion studies when plasma potassium was raised an average of 2.13 +/- 0.17 mEq/L, red blood cell sodium fell 0.61 +/- 0.10 mEq/L cells. When blood bicarbonate was raised 6.9 mEq/L by infusing NaHCO3, red blood cell sodium increased 0.79 mEq/L cells. The changes in red blood cell sodium were rapid, occurring within one hour after either of these plasma electrolyte shifts. We conclude that either plasma potassium or blood bicarbonate, or both, can serve as regulators of red blood cell sodium content in vivo, and cause the elevated level of red blood cell sodium that we have found in the DOCA-hypertensive pig. If these plasma electrolyte changes cause a similar increase in intracellular sodium in vascular smooth muscle or in a blood pressure regulating center in the brain, they may play a role in producing the arterial pressure elevation of mineralocorticoid-induced hypertension.

Animals↗

Bicarbonate uptake by basolateral membrane vesicles from rat jejunum.

Basolateral membranes from rat jejunal enterocytes have been obtained by self-orienting Percoll-gradient centrifugation. Bicarbonate and L-glucose uptake into osmotically active basolateral membrane vesicles has been studied by a rapid filtration technique. In closed vessels and at pH 8.2 the uptake kinetics of both [14C]bicarbonate and L[3H]glucose have been followed for 30 min at 18 degrees C. Bicarbonate uptake seems to be fast and in efflux experiments SITS and DIDS effect is negligible. This work demonstrates that it is possible to determine bicarbonate flux across basolateral membrane vesicles at pH and temperature values close to usual experimental conditions.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Changes in milk pH and bicarbonate during 20 days of lactation in the guinea pig.

Milk samples were obtained from lactating albino guinea pigs after 4 to 6 h of separation from their offspring. The samples were collected in 5-ml glass vials and capped immediately. They were transported rapidly to a pH-gas analyzer for measurements of pH, bicarbonate, base excess, and partial pressure of CO2. Eight guinea pigs were sampled daily for 20 d for a total of 160 observations. Analysis of variance indicated animal and day differences. Regression analyses over days revealed equations of best fit to be quadratic, although stepwise trends were observed in the data as well. The quadratic model for pH was Y(pH) = 6.996 - .057X + .002X2, where X was day of lactation (R2 = .54). The model for bicarbonate was Y (-HCO3 in milliequivalents per liter) = 8.896 - .659X + .0202X2 (R2 = .60). For base excess, the model was Y (in milliequivalents per liter) = -22.65 - 1.99X + .069X2 (R2 = .58). The model for partial pressure of CO2 was Y (millimeters of Hg) = 38.63 + 1.06X - .080X2 (R2 = .33). Decreases in pH and bicarbonate were parallel to changes in mammary epithelial cells of guinea pigs in which degeneration of mechanisms responsible for two important ingredients relating to milk volume occur. These have been identified previously as reductions in lactose and potassium. Synthesis of the enzyme carbonic anhydrase with its resultant bicarbonate production may be related in some way to these components of milk secretion.

Acid-Base Equilibrium↗

Effects of high protein diet and sodium bicarbonate supplementation on calcium metabolism in rats.

This study was conducted to determine the effect of a high protein diet on calcium metabolism in rat. Wistar strain male rats (50 days old) were divided into 5 groups (day 0): control diet (18% casein); high protein diet (18% casein +20% lactalbumin); high protein and 0.1% sodium bicarbonate diet; high protein and 0.2% sodium bicarbonate diet; and high protein and 0.4% sodium bicarbonate diet. On days 0, 1, 3, 5, 7, 9, urine samples were collected and, at the same time, feces were collected from half of the animals in each group. Urinary titratable acidity (TA-HCO3-), ammonium ion (NH4+), and net acid excretion (NAE) were measured as an index of acid-base balance in rat body. Urinary volume was rapidly increased and the increase of urinary volume continued throughout the study in rats fed the high protein diet. Urinary excretions of calcium and phosphorus were increased after day 3 and day 1, respectively, in rats fed the high protein diet. The high protein diet depressed calcium absorption and elevated phosphorus absorption from the digestive tract in rats fed the high protein diet. The high protein diet decreased TA-HCO3-, which was closely correlated with the decrease of NAE. Sodium bicarbonate supplementation to the high protein diet had little effect on urinary calcium excretion and NAE. This study suggested that there was no relationship between metabolic acidosis and hypercalciuria in rats fed the high protein diet.

Acidosis↗

Water absorption in the proximal tubule: effect of bicarbonate, chloride gradient, and organic solutes.

Simultaneous in vivo capillary and luminal microperfusion studies were performed in the superficial proximal convoluted tubule of the rat to determine the effect of intraluminal bicarbonate, the imposition of a transepithelial chloride gradient, and the addition of organic solutes to the luminal perfusion solution on the rates of water absorption (Jv). The capillary perfusion solution contained NaCl, NaHCO3, and KCl. Perfusion of both capillary and lumen with the same solution resulted in a Jv of 3.01 +/- 0.24 nl/min/mm. Imposition of a transepithelial chloride gradient (equimolar substitution of NaCl for NaHCO3 in the luminal solution) resulted in a Jv of 3.18 +/- 0.21 nl/min/mm (P = NS). Addition of cyanide to both solutions in the presence of a chloride gradient resulted in a significantly lower Jv of 2.21 +/- 0.19 nl/min/mm. Luminal substitution of Na cyclamate for NaHCO3 resulted in a solution containing no bicarbonate and no chloride gradient. Jv averaged 0.34 +/- 0.08 nl/min/mm. Addition of cyanide to the solution totally inhibited Jv. The addition of D-glucose, L-alanine, or both, to luminal solutions containing bicarbonate or in the presence of a chloride gradient did not significantly affect Jv. Addition of both organic solutes to the NaCl-Na cyclamate luminal solution resulted in a significantly higher Jv of 0.77 +/- 0.14 nl/min/mm. These studies indicate that Jv in the rat superficial proximal tubule is influenced by active sodium transport, by the presence of bicarbonate in the lumen, and/or by the imposition of a transepithelial chloride gradient. The organic solutes D-glucose and L-alanine also influence water absorption, but this effect could only be demonstrated under some experimental conditions.

Animals↗

Cholangiocyte anion exchange and biliary bicarbonate excretion.

Primary canalicular bile undergoes a process of fluidization and alkalinization along the biliary tract that is influenced by several factors including hormones, innervation/neuropeptides, and biliary constituents. The excretion of bicarbonate at both the canaliculi and the bile ducts is an important contributor to the generation of the so-called bile-salt independent flow. Bicarbonate is secreted from hepatocytes and cholangiocytes through parallel mechanisms which involve chloride efflux through activation of Cl- channels, and further bicarbonate secretion via AE2/SLC4A2-mediated Cl-/HCO3- exchange. Glucagon and secretin are two relevant hormones which seem to act very similarly in their target cells (hepatocytes for the former and cholangiocytes for the latter). These hormones interact with their specific G protein-coupled receptors, causing increases in intracellular levels of cAMP and activation of cAMP-dependent Cl- and HCO3- secretory mechanisms. Both hepatocytes and cholangiocytes appear to have cAMP-responsive intracellular vesicles in which AE2/SLC4A2 colocalizes with cell specific Cl- channels (CFTR in cholangiocytes and not yet determined in hepatocytes) and aquaporins (AQP8 in hepatocytes and AQP1 in cholangiocytes). cAMP-induced coordinated trafficking of these vesicles to either canalicular or cholangiocyte lumenal membranes and further exocytosis results in increased osmotic forces and passive movement of water with net bicarbonate-rich hydrocholeresis.

Animals↗