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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has generally been thought that homeostatic mechanisms of renal origin are responsible for minimizing the alkalemia produced by chronic hypocapnia. Recent observations from this laboratory have demonstrated, however, that the decrement in [HCO(-) (3)], which "protects" extracellular pH in normal dogs, is simply the by-product of a nonspecific effect of Paco(2) on renal hydrogen ion secretion; chronic primary hypocapnia produces virtually the same decrement in plasma [HCO(-) (3)] in dogs with chronic HCl acidosis as in normal dogs (Delta[HCO(-) (3)]/DeltaPaco(2) = 0.5), with the result that plasma [H(+)] in animals with severe acidosis rises rather than falls during superimposed forced hyperventilation. This observation raised the possibility that the secondary hypocapnia which normally accompanies metabolic acidosis, if persistent, might induce an analogous renal response and thereby contribute to the steady-state decrement in plasma [HCO(-) (3)] observed during HCl feeding. We reasoned that if sustained secondary hypocapnia provoked the kidney to depress renal bicarbonate reabsorption, the acute salutary effect of hypocapnia on plasma acidity might be seriously undermined. To isolate the possible effects of secondary hypocapnia from those of the hydrogen ion load, per se, animals were maintained in an atmosphere of 2.6% CO(2) during an initial 8-day period of acid feeding (7 mmol/kg per day); this maneuver allowed Paco(2) to be held constant at the control level of 36 mm Hg despite the hyperventilation induced by the acidemia. Steady-state bicarbonate concentration during the period of eucapnia fell from 20.8 to 16.0 meq/liter, while [H(+)] rose from 42 to 55 neq/liter. During the second phase of the study, acid feeding was continued but CO(2) was removed from the inspired air, permitting Paco(2) to fall by 6 mm Hg. In response to this secondary hypocapnia, bicarbonate concentration fell by an additional 3.0 meq/liter to a new steady-state level of 13.0 meq/liter. This reduction in bicarbonate was of sufficient magnitude to more than offset the acute salutary effect of the hypocapnia on plasma hydrogen ion concentration; in fact, steady-state [H(+)] rose as a function of the adaptive fall in Paco(2), Delta[H(+)]/Delta Paco(2) = -0.44. That the fall in bicarbonate observed in response to chronic secondary hypocapnia was the result of the change in Paco(2) was confirmed by the observation that plasma bicarbonate returned to its eucapnic level in a subgroup of animals re-exposed to 2.6% CO(2). These data indicate that the decrement in plasma [HCO(-) (3)] seen in chronic HCl acidosis is a composite function of (a) the acid load itself and (b) the renal response to the associated hyperventilation. We conclude that this renal response is maladaptive because it clearly diminishes the degree to which plasma acidity is protected by secondary hypocapnia acutely. Moreover, under some circumstances, this maladaptation actually results in more severe acidemia than would occur in the complete absence of secondary hypocapnia.
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PMID:The maladaptive renal response to secondary hypocapnia during chronic HCl acidosis in the dog. 2 Nov 98

Brook trout (Salvelinus fontinalis) urinary bladder in vitro had a low serosa-positive transepithelial potential (6.7 +/- 1.2 mV), low transmural conductance (0.23 +/- 0.03 mS. cm-2), and net absorptive transport of Na+ and Cl-. The net flux of Na+ was equivalent to that of Cl- and much larger than the membrane current, indicating neutral NaCl uptake. Na+ uptake was not coupled to that of Cl-, since absorptive Na+ transport continued in (Cl-)-free media. In the absence of Cl-, the net absorption of Na+ was accompanied by net secretion of titratable acidity, suggestive of Na+-H+ exchange on the luminal surface. Active Cl- transport persisted in dilute (2.0 mM) tetraethylammonium chloride with zero K+ and zero Na+, indicating full independence of the Cl- transport from cation coupling and suggesting the presence of Cl(-)-HCO-3 exchange. The kinetics of Cl- uptake (K1/2 = 35-37 mM, maximal transport rate = 3.0-3.4 mu eq . cm-2 . h-1) were not significantly affected by removal of mucosal Na+ . Cl- uptake was inhibited partially by 10(-4) M amiloride but not by 10(-4) M bumetanide. The results strongly support a model for active NaCl transport involving paired ion exchangers, likely located at the luminal membrane.
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PMID:Independent Na+ and Cl- active transport by urinary bladder epithelium of brook trout. 394 38

Intact rat diaphragms were exposed in vitro to varying CO(2) tensions and bicarbonate concentrations, and the steady-state citrate content of diaphragm muscle was measured to investigate the relationship between metabolism and extracellular pH, P(CO2), and (HCO(3) (-)). In addition, rat hemidiaphragms were incubated with 1,5-citrate-(14)C under different acid-base conditions, and (14)CO(2) production was determined as a measure of citrate oxidation. Acidification of the bathing medium achieved by raising CO(2) tension or lowering (HCO(3) (-)) was associated with a decrease in muscle citrate content. On the other hand, alkalinization of the medium induced by lowering CO(2) tension or raising (HCO(3) (-)) caused tissue citrate content to rise. At a physiologic extracellular pH value of approximately 7.40, citrate content was decreased or normal depending on the CO(2)/HCO(3) (-) combination employed to attain the pH. Under low bicarbonate and low P(CO2) conditions, citrate content was reduced. A similar result was found at external pH values of 7.15, implying that at these two extracellular pH levels (HCO(3) (-)) primarily determines citrate content. When changes in citrate content were compared with intracellular pH data reported earlier using the same intact diaphragm preparation, no simple relation between citrate content and intracellular pH was found. The effect of acidity on citrate content seems related to a change in citrate oxidation since the latter increased progressively with increasing degrees of medium acidity. These results show that cellular metabolism is not a simple function of extracellular pH but is dependent on the particular combination of P(CO2) and bicarbonate employed to achieve the pH value. These studies also suggest that accumulation or disposal of organic acids, such as citric acid, helps to regulate cellular acidity thereby contributing to the cells' defense against external acid-base disorders.
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PMID:The role of pH, PCO2, and bicarbonate in regulating rat diaphragm citrate content. 544 4

1. The effect of heat-stable enterotoxin (ST) of Escherichia coli, cholera toxin (CT), and theophylline (a phosphodiesterase inhibitor) on ion and water transport was studied with an in vivo isolated loop system of the pig colon.2. All three agents abolished net Na absorption as a result of a decrease in the lumen to blood Na flux alone. With all three agents, net Cl absorption was reduced, but not abolished, and net HCO(3) secretion was elicited. Luminal p(CO2) was reduced with CT and theophylline from that observed in normal Ringer alone.3. Theophylline resulted in a prompt and sustained increase in both cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP) levels in colonic mucosa studied in vitro. ST selectively elevated cyclic GMP, whereas CT selectively elevated cyclic AMP. These responses paralleled the time course and magnitude of response of the transepithelial electrical potential difference (psi(LB)) measured in vivo.4. Ion replacement studies in the presence or absence of theophylline showed that in the absence of Na, Cl absorption was slightly reduced and HCO(3) secretion was elicited; no further additive effects of theophylline in the absence of luminal Na were observed. In the absence of luminal Cl, net Na absorption was abolished and HCO(3) was absorbed; theophylline resulted in significant net Na and HCO(3) secretion. Theophylline also increased psi(LB) in the absence of either luminal Na or Cl.5. Results suggest that in the presence of theophylline or enterotoxin, the coupled Na-H and Cl-HCO(3) exchange processes that are normally responsible for at least half of the net NaCl absorption by this tissue are interrupted. Active HCO(3) secretion is observed and Cl absorption under these conditions can be entirely explained as a consequence of psi(LB). Thus, these studies indicate that the colon may participate in the production of diarrhoea of enterotoxigenic origin. They also suggest an important functional role of cyclic nucleotides in controlling the acidity and volume of colonic contents.
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PMID:Effect of Escherichia coli heat-stable enterotoxin, cholera toxin and theophylline on ion transport in porcine colon. 627 79

The influence of carbenoxolone sodium on HCO-3 transport has been examined in spontaneously alkalinizing amphibian antral (Necturus and Rana catesbeiana) and proximal duodenal (Rana catesbeiana) mucosa and in cimetidine-treated fundic mucosa (Rana temporaria) in vivo. Low concentrations of carbenoxolone (10(-6)-10(-4) mol/l, serosal side and 10(-5) mol/l, luminal side) did not affect the secretory rate or electrical properties of these tissues. In the stomach a higher concentration of carbenoxolone (10(-3) mol/l, serosal side) caused an immediate fall in transmucosal potential difference (PD) and electrical resistance. There was an initial decrease in the rate of HCO-3 transport followed by an increase in titratable alkalinization due to passive permeation of base from the serosal bathing solution. The non-steroidal anti-inflammatory agent ibuprofen (3 x 10(-3) mol/l, serosal side) inhibited alkaline secretion while the bile salt sodium taurocholate (10(-4) mol/l, luminal side) converted net alkaline secretion to a titratable acidity in cimetidine-treated fundus. Pretreatment of the mucosa with carbenoxolone (10(-4) mol/l) did not influence the response to taurocholate but when added with ibuprofen it potentiated the inhibitory effect of this drug on fundic alkaline secretion. In contrast, prostaglandin E2 (10(-6) mol/l) markedly reduced the inhibition of fundic alkaline secretion caused by ibuprofen. The anti-ulcer properties of carbenoxolone do not appear to be related to effects on gastroduodenal HCO-3 transport.
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PMID:Effect of carbenoxolone on alkaline secretion by isolated amphibian gastric and duodenal mucosa. 680 Aug 23

Administration of Ca++ (1.5 mg/kg i.v.) increased the output of both H+ and HCO-3 from the stomach of the anesthetized guinea pig as determined by measurement of gastric intraluminal pH and pCO2. The rise in HC-3 secretion was slightly greater than that in H+, resulting in a decrease in net acidity. Fundic mucosa isolated from frogs was used to study the mechanisms of the stimulatory actions. An increase in Ca++ concentration in the nutrient (serosal) bathing solution from 1.8 to 7.2 mM stimulated H+ transport in this preparation. The effect of raising Ca++ concentration was inhibited by the histamine H2 receptor antagonist Metiamide and by increasing nutrient Mg++. Stimulation of H+ transport, sensitive to Metiamide, was also observed with the calcium ionophore A23187 (4 micrograms/ml, nutrient side). The results indicate that at the mucosal level, Ca++ stimulates H+ transport by release of histamine from mucosal stores with properties similar to those of mast cells. Transport of HCO-3 in isolated mucosae was studied after inhibition of H+ transport my metiamide. An increase in nutrient Ca++ concentration stimulated the HCO-3 transport but the calcium ionophore had no effect. This action of Ca++ was abolished by atropine (10(-6) M) and by raising nutrient Mg++, suggesting that it reflects release of acetylcholine from intramucosal nervous tissue. Thus Ca++ stimulated gastric transport of both H+ and HCO-3 in vivo and in vitro but evidence for a direct action on the transporting (parietal and epithelial) cells was not obtained.
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PMID:Stimulation of gastric acid and bicarbonate secretions by calcium in guinea pig stomach and amphibian isolated mucosa. 697 50

Using the cold restrained rat model of stress ulceration, we have examined the influence of metabolic acidosis, metabolic alkalosis, and respiratory acidosis on the development of gastric erosions. The rats were restrained in tightly fitting perspex chambers at 6 degrees C for 3 hours. Acid-base imbalance was achieved by infusion of NH4Cl or NaHCO3 or by exposure to 5% CO2. The degree of ulceration was expressed by a lesion score of 0 to 4. The control group showed a score of 2.5 +/- 0.2 (mean +/- SEM). With metabolic acidosis the score was 3.6 +/- 0.2, and with metabolic alkalosis the score was 0.9 +/- 0.4. Both values were significantly different from control values (P less than 0.005). Respiratory acidosis was associated with a score similar to that of the control group. The values obtained appeared to be independent of gastric luminal acidity. The findings indicate that the systemic HCO-3 concentration is a significant determinant of the degree of ulceration in the cold restrained rat.
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PMID:Acid-base imbalance and ulceration in the cold restrained rat. 705 14

Exposure to hyperoxia (500-600 torr) or low pH (4.5) for 72 h or NaHCO(3) infusion for 48 h were used to create chronic respiratory (RA) or metabolic acidosis (MA) or metabolic alkalosis in freshwater rainbow trout. During alkalosis, urine pH increased, and [titratable acidity (TA) - HCO(-)(3)] and net H(+) excretion became negative (net base excretion) with unchanged NH(+)(4) efflux. During RA, urine pH did not change, but net H(+) excretion increased as a result of a modest rise in NH(+)(4) and substantial elevation in [TA - HCO(-)(3)] efflux accompanied by a large increase in inorganic phosphate excretion. However, during MA, urine pH fell, and net H(+) excretion was 3.3-fold greater than during RA, reflecting a similar increase in [TA - HCO(-)(3)] and a smaller elevation in phosphate but a sevenfold greater increase in NH(+)(4) efflux. In urine samples of the same pH, [TA - HCO(-)(3)] was greater during RA (reflecting phosphate secretion), and [NH(+)(4)] was greater during MA (reflecting renal ammoniagenesis). Renal activities of potential ammoniagenic enzymes (phosphate-dependent glutaminase, glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, alanine aminotransferase, phosphoenolpyruvate carboxykinase) and plasma levels of cortisol, phosphate, ammonia, and most amino acids (including glutamine and alanine) increased during MA but not during RA, when only alanine aminotransferase increased. The differential responses to RA vs. MA parallel those in mammals; in fish they may be keyed to activation of phosphate secretion by RA and cortisol mobilization by MA.
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PMID:Renal responses of trout to chronic respiratory and metabolic acidoses and metabolic alkalosis. 1044 55

We studied the role of duodenal cellular ion transport in epithelial defense mechanisms in response to rapid shifts of luminal pH. We used in vivo microscopy to measure duodenal epithelial cell intracellular pH (pH(i)), mucus gel thickness, blood flow, and HCO secretion in anesthetized rats with or without the Na(+)/H(+) exchange inhibitor 5-(N,N-dimethyl)-amiloride (DMA) or the anion transport inhibitor DIDS. During acid perfusion pH(i) decreased, whereas mucus gel thickness and blood flow increased, with pH(i) increasing to over baseline (overshoot) and blood flow and gel thickness returning to basal levels during subsequent neutral solution perfusion. During a second brief acid challenge, pH(i) decrease was lessened (adaptation). These are best explained by augmented cellular HCO uptake in response to perfused acid. DIDS, but not DMA, abolished the overshoot and pH(i) adaptation and decreased acid-enhanced HCO secretion. In perfused duodenum, effluent total CO(2) output was not increased by acid perfusion, despite a massive increase of titratable alkalinity, consistent with substantial acid back diffusion and modest CO(2) back diffusion during acid perfusions. Rapid shifts of luminal pH increased duodenal epithelial buffering power, which protected the cells from perfused acid, presumably by activation of Na(+)-HCO cotransport. This adaptation may be a novel, important, and early duodenal protective mechanism against rapid physiological shifts of luminal acidity.
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PMID:Acute adaptive cellular base uptake in rat duodenal epithelium. 1135

The cis-enol of N-acetylamino-p-methylacetophenone was generated flash photolytically and its rates of ketonization in aqueous HClO(4) and NaOH solutions as well as in HCO(2)H, CH(3)CO(2)H, H(2)PO(4)(-), (CH(2)OH)(3)CNH(3)(+), and NH(4)(+) buffers were measured. Rates of enolization of N-acetylamino-p-methylacetophenone to the cis-enol were also measured by hydrogen exchange of its methylene protons, and combination of the enolization and ketonization data gave the keto-enol equilibrium constant pK(E) = 5.33, the acidity constant of the enol ionizing as an oxygen acid pQ(a)(E)= 9.12, and the acidity constant of the ketone ionizing as a carbon acid pQ(a)(K)= 14.45. Comparison of these results with corresponding values for p-methylacetophenone itself shows that the N-acetylamino substituent raises all three of these equilibrium constants: K(E) by 3 orders of magnitude, Q(a)(E) by 1 order of magnitude, and Q(a)(K)by 4 orders of magnitude. This substituent also retards the rate of H+ catalyzed enol ketonization by 4 orders of magnitude. The origins of these substituent effects are discussed.
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PMID:Keto-enol/enolate equilibria in the N-acetylamino-p-methylacetophenone system. Effect of a beta-nitrogen substituent. 1155 5


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