Loss Of HCO3 Research Articles

Metabolic acidosis

Acid-base disorders due to different etiologies are frequently encountered in daily clinical practice and may result in life-threatening situations. Basic knowledge of the diagnostic and therapeutic approach of acid-base disorders is therefore essential for every clinician. Acid-base disorders should be treated according to their underlying etiology. Therefore, diagnosis of the underlying etiology is the critical step in the process of care for patients with acid-base disorders. Undirected buffering with HCO3 - should be avoided, since the application of HCO3 - might lead to severe side effects. A strict diagnostic pathway for the diagnosis of acid-base disorders is required, which should be vigorously applied:- analysis of the pH to classify acidemia or alkalemia- analysis of pCO2 and HCO3 - to classify the primary acid base disorder- analysis of the adequate regulation in order to detect additional acid-base disorders- analysis of the anion gap and the relationship of the anion gap vs. the change in HCO3 - to detect further metabolic disordersMetabolic acidosis can be divided into two main etiologies:- acidosis with addition of acid with increased anion gap,- acidosis with loss of HCO3 - with normal anion gap.

Safety, Tolerability, and Effects of Sodium Bicarbonate Inhalation in Cystic Fibrosis.

Among the many consequences of loss of CFTR protein function, a significant reduction of the secretion of bicarbonate (HCO3-) in cystic fibrosis (CF) is a major pathogenic feature. Loss of HCO3- leads to abnormally low pH and impaired mucus clearance in airways and other exocrine organs, which suggests that NaHCO3 inhalation may be a low-cost, easily accessible therapy for CF. To evaluate the safety, tolerability, and effects of inhaled aerosols of NaHCO3 solutions (4.2% and 8.4%). An experimental, prospective, open-label, pilot, clinical study was conducted with 12 CF volunteer participants over 18years of age with bronchiectasis and pulmonary functions classified as mildly to severely depressed. Sputum rheology, pH, and microbiology were examined as well as spirometry, exercise performance, quality-of-life assessments, dyspnea, blood count, and venous blood gas levels. Sputum pH increased immediately after inhalation of NaHCO3 at each clinical visit and was inversely correlated with rheology when all parameters were evaluated: [G' (elasticity of the mucus) = - 0.241; G″ (viscosity of the mucus) = - 0.287; G* (viscoelasticity of the mucus) = - 0.275]. G* and G' were slightly correlated with peak flow, forced expiratory volume in 1 s (FEV1), and quality of life; G″ was correlated with quality of life; sputum pH was correlated with oxygen consumption (VO2) and vitality score in quality of life. No changes were observed in blood count, venous blood gas, respiratory rate, heart rate, peripheral oxygen saturation of hemoglobin (SpO2), body temperature, or incidence of dyspnea. No adverse events associated with the study were observed. Nebulized NaHCO3 inhalation appears to be a safe and well tolerated potential therapeutic agent in the management of CF. Nebulized NaHCO3 inhalation temporarily elevates airway liquid pH and reduces sputum viscosity and viscoelasticity.

Selective photocatalytic CO2 reduction to CH4 over Pt/In2O3: Significant role of hydrogen adatom

The selectivity of photocatalytic CO2 reduction to CH4 can be enhanced over Pt-decorated semiconductors, which is commonly attributed to the fact that a Schottky junction is formed, thus enhancing photoinduced electron lifetime. However, it is difficult to understand why the yield of CO—the other product of photocatalytic CO2 reduction—is decreased only in terms of photoinduced electron lifetime. In this work, the mechanism of Pt-promoted CH4 formation was probed again in a gas-solid system of photocatalytic CO2 reduction over highly-dispersed-Pt decorated In2O3 nanorods (Pt/In2O3). It was found that the presence of Pt modulates the surface property of In2O3 due to electronic and steric effect, resulting in a loss of HCO3−, b-CO32− and m-CO32− species for the coadsorption of CO2 with H2O. However, this is not directly related with the high CH4 selectivity and low CO yield on the Pt/In2O3 photocatalysts. Photocatalytic reductions of CO, HCOOH, CH2O, and CH3OH as well as photocatalytic CO2 reduction over photocatalysts with different H2 uptakes confirm that H adatoms derived from H2 or H2O dissociation on Pt play a key role in the formation of CH4. Low H2 dissociation barrier on Pt and weak HPt bond facilitate the bonding of C in CO2 with H, thus restraining CO production. In other words, the metallic Pt acts as atomic hydrogen reservoir that supplies sufficient and readily available protons for CH4 formation over Pt-decorated semiconductors. The present work offers a new window to explore non-noble metals or their alloys with stability in air and high dissociation ability to H2 or H2O as a replacement of Pt for CO2 photoreduction to CH4.

Madam, why are you so sour?

Madam, why are you so sour?

Secretagogue-induced 86Rb+ efflux from bovine parotid is HCO3- dependent.

Muscarinic agonist (carbachol)-induced K+ loss from a bovine parotid mince was studied using 86Rb+ as a K+ marker. In contrast to our previous studies with the rat parotid [Am. J. Physiol. 261 (Gastrointest. Liver Physiol. 24): G111-G118, 1991] in which both Cl(-)-dependent and HCO3(-)-dependent components of carbachol-induced 86Rb+ efflux were observed, no significant evidence for Cl(-)-dependent 86Rb+ loss was detected in the bovine parotid. HCO3(-)-dependent agonist-induced 86Rb+ loss was blunted by K+ and Cl- channel blockers and by removal of extracellular Ca2+, consistent with the hypothesis that this 86Rb+ loss occurs via a Ca(2+)-activated K+ channel and that this cation loss serves to electrically balance the concomitant loss of HCO3- via an electrically conductive pathway, presumably an apical anion channel. Acetate, formate, and propionate could substitute for HCO3-. Interpreted in terms of current models of salivary fluid secretion, which hypothesize that the production of fluid is secondary to anion secretion accompanied by an electrically coupled K+ loss, these results indicate that salivary production in the bovine parotid is driven almost exclusively by acinar HCO3- secretion.

Regulation of electrolyte and fluid secretion in salivary acinar cells.

The primary secretion from exocrine gland cells is a fluid rich in Na+ and Cl- with a plasmalike ionic composition. Activation of specific receptors on the plasma membrane by hormones and neurotransmitters, which leads to activation of the phosphoinositol metabolism, results in release of Ca2+ from internal Ca2+ stores. Intracellular free Ca2+ concentration ([Ca2+]i) then rises simultaneously at both the basolateral and luminal parts of the acinar cell, reaching maximum values within 1 s after stimulation. In parotid acinar cells, increased [Ca2+]i activates the opening of maxi K+ channels located on the basolateral membrane and Cl- channels presumably located on the luminal membrane, resulting in rapid loss of K+ and Cl- and water and cell shrinkage. Extracellular electroneutrality is maintained by a paracellular Na+ flux into the lumen. Because of the simultaneous activation of K+ and Cl- channels, secretion occurs at a virtually constant membrane potential of about -60 mV. After maximal muscarinic cholinergic stimulation, loss of K+, Cl-, and water results in an approximate 25% reduction in cell volume within 10-15 s after receptor activation. Concomitant with loss of Cl-, there is a loss of HCO3- from the cell, causing a decrease in intracellular pH of 0.1 pH units because of the carbonic anhydrase-mediated conversion of CO2 into H+ and HCO3-. H+ generated from the metabolism and HCO3- production is compensated for by extrusion of H+ by a Na(+)-H+ exchange mechanism, which is responsible for approximately 75% of net Na+ gain that occurs after stimulation. Increased [Na+]i activates the Na(+)-K+ pump, which in turn extrudes Na+ from the cells. In both the unstimulated and stimulated states, cellular production of HCO3- can drive a net uptake of Cl- via the Cl(-)-HCO3- exchange mechanism operating in parallel with the Na(+)-H+ exchanger. The operation of the Cl(-)-HCO3- exchanger is, together with a Na(+)-K(+)-2Cl- cotransport system, essential for maintainance of a high [Cl-]i both in the unstimulated state and during Cl- reuptake.

Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial

There is still controversy over whether or not patients should be hyperventilated after traumatic brain injury, and a randomized trial has never been conducted. The theoretical advantages of hyperventilation are cerebral vasoconstriction for intracranial pressure (ICP) control and reversal of brain and cerebrospinal fluid (CSF) acidosis. Possible disadvantages include cerebral vasoconstriction to such an extent that cerebral ischemia ensues, and only a short-lived effect on CSF pH with a loss of HCO3-buffer from CSF. The latter disadvantage might be overcome by the addition of the buffer tromethamine (THAM), which has shown some promise in experimental and clinical use. Accordingly, a trial was performed with patients randomly assigned to receive normal ventilation (PaCO2 35 +/- 2 mm Hg (mean +/- standard deviation): control group), hyperventilation (PaCO2 25 +/- 2 mm Hg: HV group), or hyperventilation plus THAM (PaCO2 25 +/- 2 mm Hg: HV + THAM group). Stratification into subgroups of patients with motor scores of 1-3 and 4-5 took place. Outcome was assessed according to the Glasgow Outcome Scale at 3, 6, and 12 months. There were 41 patients in the control group, 36 in the HV group, and 36 in the HV + THAM group. The mean Glasgow Coma Scale score for each group was 5.7 +/- 1.7, 5.6 +/- 1.7, and 5.9 +/- 1.7, respectively; this score and other indicators of severity of injury were not significantly different. A 100% follow-up review was obtained. At 3 and 6 months after injury the number of patients with a favorable outcome (good or moderately disabled) was significantly (p less than 0.05) lower in the hyperventilated patients than in the control and HV + THAM groups. This occurred only in patients with a motor score of 4-5. At 12 months posttrauma this difference was not significant (p = 0.13). Biochemical data indicated that hyperventilation could not sustain alkalinization in the CSF, although THAM could. Accordingly, cerebral blood flow (CBF) was lower in the HV + THAM group than in the control and HV groups, but neither CBF nor arteriovenous difference of oxygen data indicated the occurrence of cerebral ischemia in any of the three groups. Although mean ICP could be kept well below 25 mm Hg in all three groups, the course of ICP was most stable in the HV + THAM group. It is concluded that prophylactic hyperventilation is deleterious in head-injured patients with motor scores of 4-5.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine-induced intracellular acidosis in rabbit salivary gland acinar cells

Intracellular pH (pHi) was measured in acini isolated from rabbit mandibular salivary glands using the fluorescent pH-sensitive probe 2,7-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Resting pHi was estimated to be 7.13 +/- 0.01 (mean +/- SE of 29 experiments). Stimulation with acetylcholine (ACh) caused an intracellular acidosis followed by a return of pHi toward the control value with a half time of approximately 3 min. The intracellular acidosis was dose dependent and could be abolished by pretreatment of the acini with atropine (10 microM), suggesting that it was due to a receptor-mediated event. Incubation of the acini in HCO3- -free solutions or treatment of the acini with the carbonic anhydrase inhibitor acetazolamide (1 mM) abolished the acidosis, suggesting that the acidosis might be caused by loss of HCO3- from the cell. The acidosis was not affected by either 1) pretreatment of the acini with the anion exchange inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), or 2) equilibration of the acini in Cl- -free solution (Cl- substituted with glucuronate). These results suggest that the postulated HCO3- efflux does not occur by Cl- -HCO3- exchange. However, Cl- -HCO3- exchange did appear to be present because replacement of Cl- caused a large DIDS-sensitive alkalinization of pHi, presumably caused by HCO3- uptake in exchange for Cl-. The recovery of pHi after the initial acidosis on stimulation with ACh could be blocked by 1 mM amiloride, suggesting that the recovery phase was mediated by Na+-H+ exchange.

Quantitative importance of alkalinity flux from the sediments of acid lakes

The recognition of lake acidification as an important environmental problem has recently stimulated the development of predictive models1–4 linking strong acid loading to lake pH or alkalinity. Among these models, the mass balance approach2 has been used to predict lake alkalinity from measured stream and precipitation chemistry and from watershed hydrology. This approach requires that all important positive or negative alkalinity fluxes within the system be considered. The diffusive loss of H+ to the sediments and loss of HCO3− from the sediments constitute potentially important sources of alkalinity in acid lakes. However, the relative importance of these fluxes has generally been overlooked and the presently available information appears to be limited to a few studies on the generation of alkalinity in anoxic hypolimnia3,4. The flux of alkalinity across the sediment–water interface is estimated here for one lake subject to relatively high acid deposition. For this lake, the estimated annual diffusive loss of alkalinity from the sediment to the overlying water was found to be as large as the combined measured acidity input from the watershed and from direct precipitation to the lake, thus showing the significant role of sediment–water interactions in the alkalinity balance of some acid lakes.

The role of chloride-bicarbonate exchange in the regulation of intracellular chloride in guinea-pig vas deferens.

The Cl-depleted smooth muscle cells of guinea-pig vas deferens rapidly restore their intracellular Cl activity ( aiCl ) to a level 5 times higher than that predicted by a passive distribution when Cl- ions are readmitted to the extracellular solution. Cl reaccumulation, measured using Cl-sensitive micro-electrodes and the uptake of 36Cl, was slowed about 3-fold by the nominal absence of CO2 and HCO3 and about 10-fold by the presence of the anion exchange inhibitor DIDS (4-4'-diisothiocyanostilbene-2,2'-disulphonic acid). However, the usual level of intracellular Cl was eventually attained and neither condition reduced intracellular Cl in normal tissues. The loss of intracellular Cl that occurs when Cl- ions are removed from the extracellular solution was slowed about 3-fold by the nominal absence of CO2 and HCO3 and was accelerated by their readdition. DIDS slowed the fall in aiCl about 10-fold and reduced 36Cl efflux. Intracellular pH (pHi), measured using pH-sensitive micro-electrodes, increased by a mean of 0.73 units when Cl was removed from the superfusing solution in the presence of CO2 and HCO3, and rapidly decreased when Cl was readmitted. These changes are equivalent to an intracellular accumulation and loss of HCO3- ions respectively. The net transmembrane movement of HCO3- ions which would have caused these changes in pHi was calculated using the measured intracellular buffering power ( Aickin , 1984). 25% fewer HCO3- ions than Cl- ions were accumulated and lost and the HCO3 movement was completed 2-3 times faster than the simultaneous Cl movement under the same conditions. The changes in pHi induced by alteration of extracellular Cl were reduced by the nominal absence of CO2 and HCO3 and abolished by the presence of DIDS. The acidification recorded on readmission of Cl in the nominal absence of CO2 and HCO3 was compatible with a metabolic production of about 0.1% CO2. We conclude that Cl-HCO3 exchange plays a major role in the regulation of intracellular Cl. The exchange carrier is reversible, is completely inhibited by DIDS, and accounts for about 75% of the net Cl movement that occurs when Cl is removed from or readmitted to the extracellular solution. The mechanism which is responsible for the remaining Cl movement remains to be elucidated.

Varying role of extracellular electrolytes in metabolic acidosis and alkalosis.

The responses of plasma and extracellular space to different types of acids and alkalis were studied in nephrectomized cats. Compensation for mineral acids can largely be accounted for by changes which are detectable in extracellular constituents. These changes are movement of Na+ and K+ into the extracellular space (ECS) and loss of HCO3– from the ECS. Organic acids which penetrate cells rapidly and may be expected to cause an intracellular and extracellular acidosis, produce negligible changes in extracellular content of Na and K. Alkalosis produced by NaOH or NaHCO3 was compensated for mainly by extracellular gain of bicarbonate and loss of Na. The response to NH4OH was unusual in that this alkaline solution caused an acidosis with movement of K into the ECS. The site of compensation for the various acids and alkalis was indicated by a comparison of the volume of agent infused with the change in volume of the ECS. The distribution of Na in these animals was not related as much to the concentration of Na in the ECS as it was to the pH produced by the solution infused. The response of the living organism to different types of acids and alkalis is variable and seems mainly related to the distribution of the material in the body.