Increase In Bicarbonate Concentration Research Articles

Effect of acid perfusion of the terminal ileum on plasma immunoreactive secretin and pancreatic secretion in the rat.

The distribution of immunoreactive secretin in acid extracts of the alimentary tract of the rat was determined. It was found to be contained in higher concentrations in the duodenum and in the terminal ileum than in other parts of the intestine. To elucidate the possible role of secretin contained in the terminal ileum, this part of the intestine was perfused with hydrochloric acid, a potent secretin secretagogue, and changes in plasma immunoreactive secretin levels and in pancreatic secretion were investigated in anaesthetized rats. Plasma immunoreactive secretin was increased from 65 +/- 5 pg/ml to 108 +/- 13 pg/ml during a 10 minutes perfusion with hydrochloric acid. This was significantly higher than that of saline perfusion but significantly lower than that of duodenal perfusion with hydrochloric acid. Acid perfusion of the terminal ileum also caused a three-fold increase in pancreatic flow rate and a twofold increase in bicarbonate concentration. These results suggest that the terminal ileum, through release of secretin, might play a role in regulating the pancreatic secretion of water and bicarbonate in response to changes in intraluminal fluids in the distal intestine in the rat.

Mechanisms of pancreatic hypersecretion following intraduodenal hyperosmolar glucose infusion in rats.

The effects of intraduodenal glucose infusions on pancreatic exocrine secretion were studied in anesthetized and in conscious rats with pancreatic fistula. In the anesthetized model a stimulating effect of glucose on pancreatic flow and bicarbonate output was evidenced. This effect was dose-related and depended in part upon osmolarity of the solution. No nervous mechanism could be demonstrated, while release of secretin in portal blood might be involved in the observed effect. In conscious rats an increase of bicarbonate concentration and output was observed after 30% intraduodenal glucose while protein concentration and output decreased very significantly. These effects persisted after vagotomy.

Biliary response to food in rabbits: role of the gall bladder and the enterohepatic circulation of bile salts.

The biliary response to feeding has been investigated in intact and cholecystectomized rabbits, with and without interruption of the enterohepatic circulation of bile salts. The relative contribution of the different secretory mechanisms involved in this process has been examined. Feeding induced an increase in the flow and bicarbonate concentration of the bile and a slight decrease in the bile salt content in rabbits with gall bladders and the enterohepatic circulation intact. Feeding with the enterohepatic circulation interrupted elicited a drop in bile flow and the bile salt concentration, but an increase in bicarbonate concentration. Interruption of the enterohepatic circulation thus dramatically modifies the feeding response: a response to food is still detectable after interruption, but is masked by the negative effects of drainage of the bile away from the duodenum.

Influence on cerebral blood flow of infusion of sodium bicarbonate during respiratory acidosis and alkalosis in the dog.

In anaesthetized dogs, a mixed acid-base disturbance was induced by adding a pronounced metabolic alkaline to an established respiratory acidosis or alkalosis. Cerebral blood flow (CBF) was measured by the radioisotope washout method. In the hypocapnic dogs, the addition of metabolic alkalosis did not significantly change cerebral blood flow. In the hypercapnic dogs, the intravenous infusion of alkali led to a substantial reduction of cerebral blood flow, parallelled by a reduction of cerebrovenous oxygen tension. Acid-base analysis of cerebrospinal fluid (CSF) indicated an increased bicarbonate concentration. Hypercapnia is suggested to facilitate the passage of bicarbonate over the blood-brain barrier, leading to cerebral vasoconstriction by means of increased extravascular pH.

Photosynthetic characteristics of coccoid marine cyanobacteria

Two strains of marine Synechococcus possessed a much greater potential for photorespiration than other marine algae we have studied. This conclusion was based on the following physiological and biochemical characteristics: a) a light-dependent O2 inhibition of photosynthetic CO2 assimilation at atmospheric O2 concentrations. The degree of inhibition was dependent on the relative concentrations of dissolved O2 and CO2, being greatest at 100% O2 with no extra bicarbonate added to the medium; b) actively photosynthesizing cells had high levels of ribulose-1,5-bisphosphate carboxylase compared with phosphoenolpyruvate carboxylase; ribulose-1,5-bisphosphate oxygenase activities were three times greater than ribulose-1,5-bisphosphate carboxylase activities; c) cells photosynthesizing in 21% O2, showed significant 14C-labelling of phosphoglycolate and glycolate and the percentage of total carbon-14 incorporated into these two compounds increased when the O2 concentration was 100%; d) at 100% O2, there was a post-illumination enhanced rate of O2 consumption, which was three times greater than dark respiration, and the rate declined with increasing bicarbonate concentrations. The inhibitory effect of O2 on photosynthesis did not appear to be solely due to photorespiration, since O2 inhibition of photosynthetic O2 evolution was much greater than that of photosynthetic CO2 assimilation. Also, O2 inhibition of photosynthetic O2 evolution declined only slightly with decreasing light intensities, while the inhibition of CO2 assimilation declined rapidly with decreasing light intensity.

Luminal acidification by the perfused rat cauda epididymidis.

1. Acid secretion by the rat cauda epididymidis was studied by microperfusion of the epididymal duct and by measuring the pH of the perfusate at a constant pCO(2) using a micro pH sensitive electrode. The rate of acidification was expressed as the rate of fall of intraluminal bicarbonate per cm duct per min.2. When the cauda epididymal duct was perfused with normal bicarbonate solution, the luminal bicarbonate concentration fell at a rate of 0.59 +/- 0.39 n-equiv cm(-1) min(-1) (mean +/- s.e.,n = 22).3. The rate of luminal acidification was independent of the perfusion rate but was dependent on the concentration of bicarbonate in the perfusion fluid. The rate of fall of luminal bicarbonate increased with increasing bicarbonate concentration and showed saturation at an intraluminal bicarbonate concentration of 25 m-mole/l.4. Acidification was abolished in the absence of intraluminal sodium ions. This may suggest a linked sodium reabsorption and hydrogen ion secretion.5. Acidification of the luminal fluid was studied under different acid-base conditions. In animals undergoing metabolic acidosis, the rate of acidification was enhanced, and conversely in animals undergoing metabolic alkalosis, the rate was depressed.6. Intravenous infusion of acetazolamide into rats at a dose rate of 20 mg/kg.hr markedly inhibited the acidification process. This effect was still observed in animals undergoing metabolic acidosis. Acetazolamide (10(-5)m) applied luminally was found to have no effect but higher concentration (10(-4)m) was found to inhibit acidification by 50%.7. The role of acidification of the epididymal fluid in sperm maturation was discussed.

The effect of carbonic anhydrase inhibitors on the anionic composition of sheep's parotid saliva. With an appendix on uncatalysed carbon dioxide-water kinetics by P. T. McTigue.

1. The effects of the carbonic anhydrase inhibitors, acetazolamide, ethoxzolamide and benzolamide on the ionic composition of parotid saliva were studied in anaesthetized sheep with access to the parotid blood vessels. 2. The inhibitors were infused directly into the arterial blood supply to the gland to give blood concentrations in the range 10(-5) to 10(-2) M. 3. Mean anionic concentrations at basal flow rate before inhibitor infusion were, bicarbonate 98 m-mole/l., phosphate 15 m-mole/l. and chloride 26 m-mole/l. In the presence of inhibitors, bicarbonate concentration fell by 11 m-mole/ml. and phosphate and chloride concentrations rose. Secreto-motor nerve stimulation increased bicarbonate concentration by 13 m-mole/l. before infusion of inhibitors and the concentrations of the other anions fell. The bicarbonate rise was abolished by the inhibitors and the fall in phosphate concentration was balanced by a rise in chloride concentration. 4. These effects show that only a small component of the bicarbonate ion transfer system in the sheep parotid gland is sensitive to these inhibitors. 5. The relationship of these findings to a new enzyme with carbonic anhydrase action isolated from the sheep's parotid gland is discussed.

Taurolithocholic acid and chlorpromazine cholestasis in the rhesus monkey.

Taurolithocholic acid (TLC) and chlorpromazine (CPZ) cholestasis were studied in reversible primate models in order to determine the level of injury, changes in canalicular permeability, and the effects of taurocholic acid (TC) on the production of cholestasis. TLC produced dose-dependent cholestasis. Reductions in bile acid secretion rate and concentration, larger decreases in [14C]erythritol clearance than in total bile flow, and increased bicarbonate concentration in bile indicated that the cholestasis was canalicular in origin. TC prevented cholestasis; it also caused an increased secretion of TLC in bile, but the TLC:TC concentration ratio was unchanged, providing evidence that TC is beneficial because it hastens excretion of TLC from the liver cell in micelles. Permeability to [3H]inulin was increased during the recovery period. CPZ caused reductions in bile flow, bile acid secretion rate, and [14C]erythritol clearance, and almost completely eliminated biliary bicarbonate secretion, suggesting a mixed canalicular and ductular form of cholestasis. When TC was given with CPZ, no reductions in bile acid secretion rate or [14C]erythritol clearance were found but bicarbonate secretion was markedly reduced, bicarbonate concentration diminished, and bile acid concentration increased, i.e., TC protected against the canalicular component of CPZ cholestasis and unmasked the ductular component. Permeability to inulin was increased in three of four animals. TLC cholestasis occurs predominately at the canalicular level, whereas CPZ probably affects bile flow at the ductular level as well. TC protects the hepatocyte against the effects of both agents.

Effect of parathyroid hormone on bicarbonate absorption by proximal tubules in vitro

The effect of parathyroid hormone on bicarbonate absorption was tested in rabbit proximal renal tubules perfused in vitro. In proximal straight tubules 0.05 U/ml of parathyroid hormone caused a large and reversible increase in the steady-state bicarbonate concentration in tubule fluid. Further, the rates of bicarbonate and fluid absorption (measured at faster flow rates) were inhibited approximately 50% by the hormone. We conclude that parathyroid hormone directly inhibits fluid and bicarbonate absorption by proximal straight tubules, causing an increase in the bicarbonate concentration in the tubule fluid, and we suggest that this action of the hormone contributes to the increase in renal bicarbonate excretion that is generally caused by the hormone. In proximal convoluted tubules, parathyroid hormone was previously demonstrated by other investigators to inhibit fluid and bicarbonate absorption approximately proportionally, so that there was little or no change in the bicarbonate concentration in tubule fluid. In agreement we found in the present studies that 0.05 U/ml of the hormone did not affect the steady-state bicarbonate concentration in proximal convoluted tubule fluid and that 5 U/ml caused only an equivocal increase in tubule fluid bicarbonate concentration.

ACID‐BASE RELATIONSHIPS WITHIN THE AVIAN EGG

Summary1. In the newly laid egg of the domestic fowl the pH values of the albumen and yolk are about 7.6 and 6.0 respectively.2. When the egg is stored in air there is a loss of carbon dioxide from the albumen and the pH of this fluid rises to a maximum value of about 9.5. A large proportion of the carbon dioxide which remains in the albumen is in the form of carbonate.3. In the fertile incubated egg the pH of the albumen attains a maximum value within a period of about 2 days; the albumen then becomes less alkaline and it is nearly neutral by the end of the second week. The increasing acidity of the albumen can be attributed to (a) the secretion of hydrogen ions by the blastoderm and (b) the output of carbon dioxide by developing tissues.4. During the first 2 weeks of incubation the pH of the yolk progressively increases to a maximum value of about 7.5: there is then a tendency for the pH of this fluid to fall and the yolk that is retained within the body of the hatched chick is slightly acidic.5. The embryo may never come into direct contact with either the albumen or the yolk when the pH of these fluids are high and low respectively. At the beginning of embryonic development the blastoderm is separated from the albumen by the vitelline membrane and from the yolk by a layer of subgerminal fluid with a maximum pH of about 7.8. The vitelline membrane ruptures on day 4 but by this time the embryo is bathed in amniotic fluid with a pH of about 7.5.6. The pH of amniotic fluid falls from a maximum value of about 7.5 during week I to a minimum value of about 6.5 during week 2. Amniotic fluid is a simple solution of salts until day 12; albumen then begins to flow into the amniotic cavity and the buffering capacity of amniotic fluid increases.7. The principal end‐product of nitrogenous metabolism in the chick embryo is uric acid and about 100 mg of this substance are deposited within the allantoic cavity. The pH of allantoic fluid may exceed 7.5 during week 1 but falls to 6.0 or below after day 13.8. The tension of carbon dioxide within the egg is determined by the ratio of the rate of carbon dioxide production by the embryo to the permeability of the shell towards carbon dioxide. For the greater part of the period of incubation the permeability of the shell towards carbon dioxide is constant. Thus, as the carbon dioxide output of the embryo increases, the carbon dioxide tension within the egg rises.9. The pH of the blood can be defined in terms of the ratio of the bicarbonate concentration to the carbon dioxide tension. There is a progressive increase in the carbon dioxide tension of the blood during the period of incubation but the pH is maintained at about 7.4 by an increase in bicarbonate concentration.10. Part of the increase in bicarbonate is due to the removal of hydrogen ions from carbonic acid by haemoglobin. There is also a large influx of bicarbonate into the blood, but the source of this bicarbonate is not known; the evidence that renal mechanisms are involved is inconclusive and it is probable that the embryo utilizes the enormous potential store of bicarbonate in the egg shell.

The influence of bicarbonate administration on blood pH in a “closed system”: Clinical implications

An in vitro comparison was made of the effect of isotonic and hypertonic NaHCO 3 solutions on blood pH when the elimination of carbon dioxide was prevented. The results demonstrate that the rise in P co 2 which occurs after addition of isotonic NaHCO 3 offsets the increase in bicarbonate concentration, and the rise in pH is extremely small. The addition of bicarbonate in hypertonic solutions produces a greater elevation of P co 2 and blood pH may actually fall. The acidosis associated with hypertonicity of extracellular fluids results from the dilution of extracellular buffers and the release of protons from intracellular buffers, such as hemoglobin, in response to the increase in ionic strength.

Choleresis induced by secretin: distinctly increased response in cirrhotics.

The effect of secretin infusion on choleresis was studied in 3 patients with cirrhosis of the liver and 6 patients with no signs of liver disease. All patients had undergone biliary surgery with a balloon-equipped T-tube left in the common bile duct. In the cirrhotics, resting bile flow was slightly higher than in the control group. The response of hepatic bile to secretin infusion was markedly higher in the cirrhotics (5 to 10-fold). In addition, in patients with liver cirrhosis, secretin caused a pronounced increase of bicarbonate concentration with an equimolar fall in chloride concentration in the bile, while there was hardly any effect in this respect in the group with normal livers. The marked stimulatory effect of secretin on duodenal juice production in cirrhotics observed in earlier studies on exocrine pancreatic function can be explained by the high volume response of bile flow reported here. It is assumed that increased sensitivity of the bile duct epithelia in the cirrhotic liver to secretin stimulation is the most important factor for this effect.

Effects of parenteral hyperalimentation on upper gastrointestinal tract secretions.

We have collected gastric and duodenal drainage in five mongrel dogs. During the administration of secretin and pancreozymin, parenteral hyperalimentation significantly decreased the volume of duodenal fluid by; 50.5%; excretion of bilirubin by 86.2%; secretion of amylase by 70.8%; content of protein in duodenal fluid by 73.1%; and increased bicarbonate concentration in duodenal fluid by 18.2%. The P values for the reductions in duodenal fluid volume and amylase were much less than 0.0005. No uniform change in gastric secretory volume or pepsin occurred. Parenteral hyperalimentation promotes healing of high enterocutaneous fistulas by producing positive nitrogen balance. In addition, it favors healing of such fistulas by decreasing the volume and modifying the content of digestive secretions. By virtue of the later effect, parenteral hyperalimentation may be beneficial in the management of other upper gastrointestinal tract, biliary, and pancreatic diseases.

PH of cerebrospinal fluid in the cisterna Magna and on the surface of the choroid plexus of the 4th ventricle and its effect on ventilation in experimental disturbances of acid base balance. Transients and steady states.

In cats anesthetized with chloralose urethane, the arterial pH and the pH either in the cisterna magna or on the surface of the choroid plexus of the 4th ventricle as well as the tidal volume, expiratory CO2 partial pressure and arterial pressure were continuously recorded. Transients and steady states were observed after the inhalation of CO2, and the i.v. injection of HCl, NaHCO3, NH4Cl, and (NH4)2CO3. 1. pH on the surface of the choroid plexus follows changes in arterialpco2 almost instantaneously. 2. Injection of HCl into the blood is followed by a transient increase in endtidalpco2 and at the same time by a transient decrease of pH on the surface of the plexus. 3. After i.v. injection of NH4Cl and (NH4)2CO3 an abrupt increase of pH on the surface of the choroid plexus is observed indicating instantaneous permeation of NH3 from the blood into the CSF. This is in agreement with the distribution theory of the early phase of NH4Cl acidosis proposed by the authors in an earlier paper. 4. If the pH is measured in the cisterna magna all reactions are much slower but are in the same direction. 5. In the steady state of respiratory acidosis, the change of pH on the surface of the choroid plexus is less than that of the blood. 6. In metabolic acidosis and alkalosis only minimal—if any—changes of pH on the surface of the choroid plexus can be demonstrated, indicating that the regulation of plexus pH in these instances is very accurate. 7. In respiratory as well as in metabolic disturbances it would seem from the observed data that even in the first few minutes some bicarbonate exchange between the blood and the CSF occurs. 8. The increase of bicarbonate concentration in the CSF after i.v. injection of ammonium salts is mainly the result of the NH3 entering the CSF and reacting with H2CO3.

Choleresis Induced by Stimulation of the Gastric Antrum

Summary The volume and composition of bile were studied by cannulation of the common bile duct through a duodenal fistula in dogs with separated antral pouches, cholecystectomy, and either total gastrectomy with Heidenhain pouch or gastrojejunostomy with gastric fistulas. Perfusion of the antral pouch with buffered acetylcholine solution at pH 7.0 caused a choleresis characterized by increased bicarbonate concentration and output, as well as increased gastric acid secretion. These effects were not seen during antral perfusion with acetylcholine chloride solution acidified to pH 1.0. These studies indicate that the antral mucosa is the source of a choleresic substance, and they are consistent with the hypothesis that this substance is gastrin.

THE FORMATION OF ACETOACETATE FROM ACETYL COENZYME A, MALONYL COENZYME A, AND PYRUVATE BY WASHED MITOCHONDRIA ISOLATED FROM GUINEA PIG LIVER

Washed mitochondria isolated from guinea pig liver were capable of synthesizing acetoacetate from pyruvate. Both acetyl-CoA and malonyl-CoA were incorporated into acetoacetate in the presence of pyruvate. However, without pyruvate, only acetyl-CoA was incorporated to any significant extent. Tracer experiments indicated that although malonyl-CoA was incorporated into acetoacetate, increased acetoacetate synthesis in the presence of pyruvate plus malonyl-CoA resulted primarily from increased pyruvate incorporation.The results of the present experiments indicated that a CO2fixation step was involved in the conversion of pyruvate to acetoacetate. Evidence in favor of this was based on the inhibitory effects of avidin (with partial reversal by biotin), stimulation with increasing bicarbonate concentration, and increased acetoacetate synthesis in the presence of malonyl-CoA.Sulphydryl binding agents completely inhibited acetoacetate synthesis from pyruvate. In the formation of acetoacetate, carbon atom 1 of pyruvate was eliminated. This indicated that pyruvate was converted into an active 2-carbon unit.

THE FORMATION OF ACETOACETATE FROM ACETYL COENZYME A, MALONYL COENZYME A, AND PYRUVATE BY WASHED MITOCHONDRIA ISOLATED FROM GUINEA PIG LIVER

Washed mitochondria isolated from guinea pig liver were capable of synthesizing acetoacetate from pyruvate. Both acetyl-CoA and malonyl-CoA were incorporated into acetoacetate in the presence of pyruvate. However, without pyruvate, only acetyl-CoA was incorporated to any significant extent. Tracer experiments indicated that although malonyl-CoA was incorporated into acetoacetate, increased acetoacetate synthesis in the presence of pyruvate plus malonyl-CoA resulted primarily from increased pyruvate incorporation.The results of the present experiments indicated that a CO2fixation step was involved in the conversion of pyruvate to acetoacetate. Evidence in favor of this was based on the inhibitory effects of avidin (with partial reversal by biotin), stimulation with increasing bicarbonate concentration, and increased acetoacetate synthesis in the presence of malonyl-CoA.Sulphydryl binding agents completely inhibited acetoacetate synthesis from pyruvate. In the formation of acetoacetate, carbon atom 1 of pyruvate was eliminated. This indicated that pyruvate was converted into an active 2-carbon unit.