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Marked increase in urinary bicarbonate and pH caused by heavy muscular exercise with dynamic knee extension.

In order to estimate the physiological responses to heavy muscular exercise with dynamic knee extension, the levels of urinary variables such as bicarbonate, urinary pH and blood lactate were studied before and after the exercise. Nine male volleyball players aged 19 or 20 years were involved in the present study. They performed 10%, 30% and 80% 1 repetition maximum (RM) knee extension. The levels of urinary bicarbonate and urinary pH did not change for 2.5 hours after cessation of the exercise with 10% 1 RM load, compared with the baseline levels. When 30% 1 RM loading was given, urinary bicarbonate and pH moderately increased for 2.5 hours. When 80% 1 RM loading was given, both urinary bicarbonate and pH increased immediately after cessation of the exercise, for 2.5 hours. Levels of blood lactate increased extensively within 1 minute after cessation of the exercise in the subjects with 80% 1 RM load, but no significant increase was seen in subjects with 10% 1 RM load. The changes in urinary bicarbonate and pH could be explained by the continuous production of CO2 in the muscular tissues involved in the exercise with a submaximal load where excess postexercise oxygen consumption is accelerated. It is also possible that the liver and muscle where blood lactate is aerobically metabolized could be the cause of these changes. It was also suggested that the measurement of urinary bicarbonate and pH may be useful for the estimation of events in the body after submaximal exercise loading.

Adult↗

Immunoreactivity to a monoclonal antibody (OS-3) is shared by osteoclasts and bicarbonate-secreting cells.

OS-3, a monoclonal antibody raised against macrophagic cells derived from cultured rat glomeruli, reacts with the plasma membrane of various bicarbonate-secreting cells such as epithelial cells of the pancreatic excretory duct and type B intercalated cells of the kidney, suggesting that the antigenic molecule of OS-3 is involved in bicarbonate production and/or secretion. Since osteoclasts must vigorously extrude bicarbonate to maintain cytoplasmic pH in a physiologic range during proton secretion, we examined the localization of OS-3 immunoreactivity in the bone tissue to determine the involvement of the detected molecule in the transmembrane transport of bicarbonate in osteoclasts. The OS-3 selectively stained the basolateral plasma membrane of osteoclasts. Ultrastructurally, the immunoreactivity with OS-3 was associated with small cytoplasmic projections and microplicae of the basolateral plasma membrane. This finding suggests that osteoclasts express the molecule common to bicarbonate-secreting cells to utilize it for bicarbonate transport during bone resorption.

Animals↗

Nature and biological significance of free radicals generated during bicarbonate hemodialysis.

This study investigates evidence of oxidative stress during bicarbonate hemodialysis by measuring total glutathione and lipid peroxidation products in plasma, and characterizes the free radicals produced by neutrophils from healthy volunteers when incubated in vitro with increasing concentrations of bicarbonate. Blood samples were taken from nine hemodialysis patients before and after two hemodialysis sessions. Plasma hydroperoxides and total glutathione were measured. A significant increase was found in total glutathione (1.04 +/- 0.4 versus 2.11 +/- 0.9 microM, P < 0.001) and hydroperoxides by ferrous oxidation in xylenol orange version 2 method (4.6 +/- 0.53 versus 6.4 +/- 0.63 microM, P < 0.001) after hemodialysis, which indicated increased oxidative injury during hemodialysis. Normal neutrophils, activated by contact adhesion, produced a dose-dependent increase in free radical production (measured by luminol-enhanced chemiluminescence) when incubated with increasing concentrations of bicarbonate (up to 35 mM). Bicarbonate had the same effect on the chemiluminescence of a cell-free hypoxanthine/acetaldehyde system generating superoxide, but not on a glucose oxidase/myeloperoxidase system generating hydrogen peroxide and hypochlorous acid. These findings are consistent with (1) the hypothesis that superoxide generated during hemodialysis reacts with bicarbonate to form the toxic carbonate and formate radicals and (2) our previous observation that some patients undergoing bicarbonate (but not lactate) dialysis have increased plasma concentrations of formate after hemodialysis. It is suggested that the increased plasma total glutathione and hydroperoxide concentrations are a result of lipid peroxidation by these species. These reactive radicals can initiate lipid peroxidation and contribute to the cardiovascular complications of hemodialysis patients.

Aged↗

Higher venous bicarbonate concentration associated with hypoxemia, not acute mountain sickness, after ascent to moderate altitude.

BACKGROUND: The pathophysiology underlying acute mountain sickness (AMS) and excessive hypoxemia at high altitudes is not fully understood. Previous work by our group has demonstrated a significant association between urinary measures of dehydration and bicarbonate retention in subjects developing excessive hypoxemia and AMS at high altitudes. To further characterize these findings, we returned to our original testing site to examine the hypothesis that subjects with lower levels of oxygen saturation and/or AMS would possess higher levels of venous bicarbonate. METHODS: Medical history inquiry, clinical examination, Lake Louise scoring, and the collection of venous levels of bicarbonate concentration and base excess were performed on 52 lowland-dwelling persons after they completed a religious pilgrimage in the Nepal Himalayas to approximately 4,250 m. RESULTS: Oxygen saturation levels were strongly and inversely correlated with serum levels of venous bicarbonate and base excess, whereas AMS and Lake Louise scores were not associated with these measures of alkalosis. CONCLUSIONS: Our data suggest an association between measures of serum bicarbonate anion retention and decreasing oxygen saturation. Our data do not demonstrate an association between AMS or Lake Louise scores and measures of serum bicarbonate level. We propose that excessive hypoxemia at high altitudes may be associated with a compromised ability of the kidney to metabolically compensate for an altitude-induced hypocapnic alkalosis.

Adult↗

Duodenal mucosal bicarbonate secretion in humans: a brief review.

The human proximal duodenum serves as the crucible for the neutralization of gastric acid. Methods have been developed and validated that permit isolation of 4-cm segments of either the proximal or distal duodenum. These isolated segments were free of contamination from gastric, pancreatic, and biliary secretions. At rest the healthy human proximal duodenum produced approximately 175 mumol cm-h: or, assuming that the duodenal bulb is approximately 4 cm in length, 700 mumol h. The distal duodenum (the third part) produced significantly less bicarbonate, approximately 25 mumol/cm-h. HCl produced a prompt and sustained increase in bicarbonate output from both duodenal segments. Bicarbonate output was less in the distal duodenum, indicating a proximal-to-distal gradient. Synthetic prostaglandin E1 caused a dose-related increase in output. Substitution of the NaCl perfusate with Na2SO4 produced a brief decrease, suggesting a chloride bicarbonate exchange mechanism. Vasoactive intestinal polypeptide significantly increased proximal duodenal bicarbonate output. Bicarbonate production by the duodenal mucosa is probably an important defensive factor in maintaining mucosal integrity.

Alprostadil↗

Mechanism of ursodeoxycholic acid- and canrenoate-induced biliary bicarbonate secretion and the effect on glucose- and amino acid-induced cholestasis.

The mechanism of ursodeoxycholic acid (UDCA)- and canrenoate-induced bicarbonate choleresis was studied before and during the administration of glucose or amino acids in anaesthetized pigs. Previous studies have shown that the canalicular secretion has, on a molar basis, a relationship among the secretion of chloride, bicarbonate, and bile acids of 0.9, 0.3, and 1, respectively. Ductular secretion is associated with the transport of 0.25 mol chloride per 1 mol bicarbonate. In control experiments UDCA was associated with a biliary secretion of about 1.3 mol chloride and 0.5 mol bicarbonate per 1 mol bile acid, and canrenoate caused the secretion of 1.2 mol chloride per 1 mol bicarbonate. Intravenous infusion of glucose or amino acids increased these relationships, and after administration of UDCA or canrenoate, these relationships were still increased by at least 70% on average when compared with the control experiments. A reduction in bile secretion after glucose or amino acid infusion is opposed by UDCA or canrenoate. The effect of UDCA or canrenoate on bile secretion is not disturbed by glucose or amino acids. Both substances stimulate canalicular bicarbonate secretion and could be of importance in improving cholestatic conditions.

Amino Acids↗

Does antral distension inhibit gastric acid secretion or stimulate bicarbonate secretion in 'healthy' subjects?

The effects of a 150-ml antral balloon distension on pentagastrin-stimulated gastric acid secretion and bicarbonate secretion were studied in nine healthy subjects and eight duodenal ulcer (DU) patients. The gastric secretions were simultaneously measured, using a luminal perfusion and pH/PCO2 measurements. Two of the healthy subjects and six of the DU patients were positive for Helicobacter pylori. When H. pylori-positive and -negative subjects were compared, basal gastric acid and bicarbonate outputs did not differ significantly. In H. pylori-infected subjects the bicarbonate transport increased by about 70% on pentagastrin stimulation. In the H. pylori-negative group pentagastrin had no effect on the bicarbonate secretion. Antral distension elicited a 30-35% inhibition of pentagastrin-stimulated gastric acid secretion in the group of H. pylori-negative subjects, whereas the acid secretory level remained essentially unchanged in the positive group. Bicarbonate secretion decreased transiently by the distension in the negative subjects, whereas a slight increase was observed in the infected group. We conclude that antral distension inhibits pentagastrin-stimulated gastric acid output in healthy H. pylori-negative subjects. Our results strongly suggest that the underlying mechanism is a direct inhibition of gastric parietal cell function and not an increased gastric bicarbonate secretion. Furthermore, the results indicate that this defective distension-induced acid inhibition may be correlated to H. pylori infection rather than to duodenal ulcer disease.

Adult↗

The effect of gastrin-releasing peptide on porcine pancreaticobiliary bicarbonate secretion is mediated by secretin.

The effect of gastrin-releasing peptide (GRP) (250, 500, 1000 pmol/kg.h) on the pancreaticobiliary bicarbonate secretion, the pancreatic protein secretion, and the plasma concentrations of secretin and cholecystokinin (CCK) was studied in the anaesthetized pig. Infusion of GRP (1000 pmol/kg.h) increased the portal plasma concentrations of secretin from 0.9 to 13.6 pmol/l and CCK from 1.2 to 38.4 pmol/l, the pancreatic bicarbonate secretion from 0.01 to 5.6 mmol/h, the hepatic bicarbonate secretion from 0.5 to 4.1 mmol/h, and the pancreatic protein secretion from 3 to 680 mg/h. Blocking of CCK-A receptors by MK-329 did not significantly change the effect of GRP, whereas prevention of secretin release by removal of the small intestine caused a 13-fold reduction in the GRP-induced pancreatic bicarbonate secretion and completely abolished the effect on hepatic bicarbonate secretion but did not change the effect on pancreatic protein secretion. We conclude that the effect of GRP on pancreaticobiliary bicarbonate secretion is not mediated through the release of CCK but more likely through the release of secretin and that the effect on pancreatic protein secretion is possibly a direct effect of GRP.

Animals↗

The pH/PCO2 method for continuous determination of human gastric acid and bicarbonate secretion. A validation study.

BACKGROUND: The present paper describes and evaluates a methodologic approach for registration of the fast, interdigestive, motility-related changes in gastric acid and bicarbonate outputs seen in man. METHODS: The technique is based on continuous gastric luminal perfusion and measurements of pH and PCO2 in gastric effluent and concomitant intragastric/duodenal manometry. Fourteen healthy volunteers participated. RESULTS: Direct acid secretory estimations from pH recordings, corrected for hydrogen ion activity, correlated closely with values obtained by conventional titration. After intragastric infusion of bicarbonate, 96 +/- 5% of the newly measured steady-state value was registered virtually instantaneously provided that corrections for the PCO2 electrode time constant and the perfusion/aspiration time were made. In the neutral pH range (pH 5-7), practically full quantitative recovery of intragastrically infused bicarbonate was obtained. In the acid pH interval (pH 2-5) the recovery was significantly lower (53 +/- 6%; p < 0.01). With an aspirate without air admixture and during high perfusion rates (31 and 46 ml/min), full recovery of bicarbonate was obtained also at an acid pH, whereas a reduced perfusion rate (16 ml/min) significantly (p < 0.05) reduced the recovery rate. CONCLUSIONS: With the pH/PCO2 technique both acid and bicarbonate assessments have a close to on-line time resolution. Acid output is measured accurately, but the method potentially underestimates actual bicarbonate levels in the acid pH range, a combined effect of diffusion of CO2 into air bubbles in the aspirate and into the gastric mucosa from the lumen. A high gastric perfusion rate minimizes this source of error. The pH/PCO2 technique is well suited for studies of the interaction between secretion and motility in the human stomach.

Adult↗

Cigarette smoking inhibits acid-stimulated duodenal mucosal bicarbonate secretion.

OBJECTIVE: To determine the effect of cigarette smoking on proximal duodenal mucosal bicarbonate secretion, an important defense mechanism against acid and peptic damage. DESIGN: Prospective study. SETTING: Clinical research laboratory in a university hospital. PATIENTS: Thirteen healthy adults (7 smokers and 6 nonsmokers) who had no history of peptic ulcer disease. INTERVENTIONS: Participants smoked (1 cigarette/15 min during a period of 1 hour, smokers only) or sham smoked (puffing on an unlit cigarette) during duodenal perfusion with either saline, hydrochloric acid, or prostaglandin E2 (PGE2). MEASUREMENTS: Collection of proximal duodenal secretions using a modified duodenal tube with occluding balloons and quantitation of duodenal mucosal bicarbonate secretion. RESULTS: During sham smoking both smokers and nonsmokers had comparable basal as well as H(+)-stimulated and PGE2-stimulated duodenal mucosal bicarbonate secretion. Compared with sham smoking, smoking did not significantly alter basal bicarbonate secretion (201 mumol/cm per hour [95% CI, 152 to 250 mumol/cm per hour] compared with 178 mumol/cm per hour [CI, 134 to 222 mumol/cm per hour], respectively). However, compared with sham smoking, smoking markedly reduced (P < 0.01) the increase in duodenal bicarbonate secretion in response to luminal acidification by approximately 80% (from 242 mumol/cm per hour [CI, 41 to 443 mumol/cm per hour] to 53 mumol/cm per hour [CI, -107 to 197 mumol/cm per hour]); a decrease was observed in each participant. In contrast, smoking had no significant effect on the response to luminal PGE2. CONCLUSIONS: Cigarette smoking markedly inhibited acid-stimulated human duodenal mucosal bicarbonate secretion. This adverse effect of smoking may, at least in part, explain the role of cigarette smoking in the pathogenesis and natural history of duodenal ulcer disease.

Adult↗

Renal function following sea snake venom (Lapemis hardwicki) administration in dogs treated with sodium bicarbonate solution.

The effects of sea snake venom (SSV) on renal function were studied in two groups of anesthetized experimental dogs pretreated with intravenous infusion of 4.2 gm% NaHCO3 solution. Animals were envenomated by intramuscular injection of SSV at a dosage of 0.34 mg/kg. Systemic hemodynamics showed no significant changes except for a tendency of decrease in cardiac output (CO). The glomerular filtration rate (GFR), the rate of urine flow (V) and effective renal plasma flow (ERPF), and effective renal blood flow (ERBF) significantly decreased, while filtration fraction (FF) significantly increased at 180 min after envenomation. Envenomated animals showed a reduction in renal fraction (RF), while renal vascular resistance (RVR) increased stepwise throughout the experimental periods. Animals pretreated with sodium bicarbonate showed no significant changes of CO, TPR MAP, HR, and packed cell volume (PCV) while receiving sea snake venom. Animals pretreated with sodium bicarbonate showed no changes in GFR, ERPF, ERBF, RF, and RVR after envenomation. The rate of urine flow markedly increased in envenomated animals which received pretreatment with bicarbonate. After envenomation alone, there were no differences in the plasma concentration of sodium (PNa) and chloride (PCl) as compared to the control value, whereas the plasma concentration of potassium (PK) increased at 180 min after envenomation. Animals pre-treated with bicarbonate showed a stepwise increase in both UNaV, FE(NA), U(Cl)V, and FE(Cl) accompanying SSV injection. Neither PNa nor PCl were affected, while PK significantly decreased in animals given SSV with bicarbonate loading. UKV and FEK increased stepwise in envenomated animals treated with bicarbonate throughout the period of study. All groups of animals given SSV, with or without NaHCO3 infusion, showed a marked elevation of the concentration of urinary myoglobin (U(Mb)), plasma lactate dehydrogenase (LDH), and plasma creatine phosphokinase (CPK) throughout experimental periods. The urinary myoglobin excretion markedly increased in animals after SSV injection accompanied by NaHCO3 infusion. It can be concluded that large amounts of myoglobin present in the renal tubules in envenomated animals can precipitate, particularly under acidic conditions, resulting in increased intratubular pressure and subsequently decreased renal hemodynamics including GFR and ERBF. An infusion of NaHCO3 to render urine more alkaline could have a protective role against depression of renal function following sea snake venom administration.

Animals↗

[Renal response to intravenous administration of sodium bicarbonate in newborn infants of different gestational ages].

The study comprised a series of 16 neonates made up of 5 patients of 33 weeks of gestation, 5 infants of 35 weeks and 6 more of 40 weeks of gestation. Blood pH, PaCO2 and HCO3- were measured together with bicarbonate, ammonium, titrable acidity and hydrogen ions in urine before and after intravenous infusion of sodium bicarbonate. Before infusion of bicarbonate, titrable acidity, ammonium and net acidity in urine were higher in accordance with a greater gestational age. As the administration of bicarbonate elapsed, titrable acidity, ammonium and net acidity dropped with increase in concentration of bicarbonate. A hypothesis is set forth that the differences found in the factors evaluated in urine before administration of bicarbonate depend on the physiologic characteristics set in the newborn by gestational age.

Bicarbonates↗

Bicarbonate solutions: update.

The use of lactate-based peritoneal dialysis solutions (PDFs) requires hepatic metabolism to convert lactate to bicarbonate. Pure bicarbonate solutions are particularly useful in the setting of hepatic dysfunction and whenever a high risk of lactate accumulation in the blood exists. This article reviews the recent literature related to laboratory findings and clinical experiences with bicarbonate-containing PDFs. The data suggest that bicarbonate-based solutions are safe and well tolerated and that, among patients with severe metabolic acidosis, they provide better correction of that acidosis than do lactate-containing PDFs. In addition, use of bicarbonate solution seems to be associated with improved nutrition, better growth rate in children with end-stage renal disease, better preservation of residual renal function, and, possibly, higher peritoneal ultrafiltration and a lower peritonitis rate. More experience with these solutions and more prospective controlled studies should be encouraged to further characterize the potential benefits of bicarbonate solutions.

Acidosis↗

[Status of the bicarbonate-mucous barrier in patients with gastroduodenal pathology].

An important role in the protection of the gastric and duodenal mucosa is played by bicarbonates. Gastric secretion of bicarbonates was examined in 42 patients with gastroduodenal pathology. Basal secretion of bicarbonates by the stomach was approximately the same (0.84 +/- 0.07 mmol/h) in patients with chronic gastritis, gastroduodenitis and peptic ulcer. After stimulation of gastric glands with a 5% alcoholic solution gastric secretion of bicarbonates increased in patients with chronic gastritis whereas in patients with peptic ulcer and gastroduodenitis, it significantly reduced. A inverse relationship was discovered between bicarbonate production and hydrochloric acid secretion. In patients with peptic ulcer, the reduction of bicarbonate and mucus output by the stomach is viewed as one of the mechanisms of ulcerogenesis.

Adolescent↗

[Bicarbonate instead of lactate buffered substitution solution for continuous hemofiltration in intensive care].

The substitution fluids applied in continuous haemofiltration contain 40 mmol/l of lactate. This is unphysiological, since administration of large amounts of lactate lowers the phosphorylation potential and increases catabolism. With bicarbonate-buffered fluid three problems may arise: 1. Precipitation of calcium carbonate and magnesium carbonate; 2. pH is usually 8.4; 3. evaporation of CO2 increases pH. To solve these problems we applied a two-component system consisting of a glass bottle with 160 ml sodium bicarbonate 8.4% and a bag with 4.5 l of acidic solution. Prior to use, the bicarbonate was infused into the bag. The values of Ca++, Mg++, bicarbonate, and pH in this final substitution solution were constant during a 24 hr period after mixing. Precipitation of Ca++ and Mg++ carbonate was prevented by 3 mmol/l of lactic acid in the solution. The pH was 7.37. Evaporation of CO2 was prevented by bags made of special plastic sheeting. The solution was then applied in 7 intensive-care patients suffering from acute renal failure treated by continuous arteriovenous haemofiltration. No side effects of the solution were observed during six days of treatment. The values of Ca++, bicarbonate, pH, and pCO2 remained constant under clinical routine conditions. Hence, bicarbonate-buffered substitution solution is recommended for continuous haemofiltration. Continuous haemofiltration is now also available for patients with impaired liver function and increased lactate levels.

Acid-Base Equilibrium↗

In vivo bicarbonate deficiency and insulin dissolution.

Exogenous insulin exists primarily as the monomer in human plasma. However, in U100 regular insulin formulations, the concentrations of zinc and peptide are such that the insulin hexamer predominates. The biologic result is further disassociation to the monomer after subcutaneous or i.v. administration. Because of this, human plasma from seven normal controls dissolved 20-30 microm hexagonal insulin crystals in 3-8 min. This ability was inhibited by acid titration to a stable pH of 6.30, at which point bicarbonate depletion could be suggested. Repletion of bicarbonate remarkably restored the solvent effect, while back-titration to the initial pH without repleting bicarbonate had only a moderate result. To establish whether the in vivo reduction of bicarbonate in pathologic states had similar results, plasma from five Type I diabetics in severe acidosis (pH 7.06 +/- 0.04, HCO3 -7.3 +/- 0.6 mmol/l) was similarly studied after stabilization under 5% CO2 (pH, 6.97-7.17). In all cases, the dissolution of insulin crystals was inhibited (dissolution times greater than 25 min). When bicarbonate was replenished (HCO3- 24.1-26.7 mmol/l) and pH accordingly renormalized (pH 7.39-7.43), the dissolution of insulin crystals was completely restored. Because of these observations, we conclude that both plasma bicarbonate and pH markedly affect the dissolution of insulin and that reduced bicarbonate/pH in diabetic ketoacidosis may limit the availability of the biologically active monomer. These influences may play a role in the initial insensitivity to insulin frequently seen in severe insulin deficiency and ketoacidosis.

Adult↗

Influence of left ventricular function on changes in plasma volume during acetate and bicarbonate dialysis.

The effect of left ventricular function on changes in plasma volume during acetate and bicarbonate dialysis was studied in stable, chronic dialysis patients. Preservation of plasma volume in patients with a normal left ventricular function (mean circumferential fibre shortening velocity (VcF) greater than or equal to 1 circ/s) was significantly less during the first hour of acetate dialysis than during bicarbonate dialysis. However, in patients with impaired left ventricular function (VcF less than 1 circ/s) the decrease in plasma volume was more pronounced during acetate when compared to bicarbonate dialysis. This resulted in a decreased ultrafiltration volume and haemodynamic instability in these patients during acetate dialysis. The fibre shortening velocity increased during acetate and bicarbonate dialysis in patients with a normal left ventricular function, whereas in patients with impaired left ventricular function fibre shortening velocity increased only during bicarbonate dialysis. In conclusion, in patients with an impaired left ventricular function, bicarbonate is preferable to acetate in chronic dialysis.

Acetates↗

Bicarbonate sensitivity of rabbit corneal endothelium fluid pump in vitro.

Stroma-endothelium preparations from rabbit corneas were mounted between two chambers and incubated with identical media on either side which contained different bicarbonate levels and, in some experiments, organic (Good's) buffers. Active fluid flow across the preparations was measured by means of a capillary tube attached to the stroma-side chamber. With media containing 2 to 50 mM bicarbonate (pH 6.2 to 7.8 in equilibrium with 5% CO2-air at 37 degrees C), the fluid pump was constant for at least 3 hr at a rate of 5 microliter/hr cm2 and was not significantly affected by the bicarbonate level. Over the same range of pH and bicarbonate but supplemented with 50 mM organic buffer, fluid pump was 8 microliter/hr cm2 for all bicarbonate concentrations used. Using Ringer solutions supplemented with 50 mM buffer (pH 6.3 to 8.4) but without added bicarbonate and in equilibrium with air, fluid pump was observed at approximately 4 microliter/hr cm2 at pH 6.3 and increased to 8 microliter/hr cm2 at pH 7.8. In all cases, fluid pump persisted for at least 5 hr.

Animals↗