Acid Secretion In Stomach Research Articles

The clinical importance of hypochlorhydria (a consequence of chronic Helicobacter infection): Its possible etiological role in mineral and amino acid malabsorption, depression, and other syndromes

In a previous paper evidence was presented to show that Helicobacter-induced chronic gastritis is the probable cause of most chronic hypochlorhydria. In this article evidence is presented for the clinical relevance of reduced stomach acid secretion. Reduced mineral absorption is fairly well documented and has sound theoretical support from basic chemistry. Impaired digestion of protein has been suggested by a few studies. Small intestinal bacterial overgrowth in hypochlorhydria probably leads to putrefactive breakdown of the metobolically useful products of protein digestion, thereby reducing their availability for certain essential pathways. The possible lowering of tryptophan, tyrosine, and phenylalanine in the blood may be a precipitating factor in depression in hypochlorhydric patients. In reduced or absent stomach acid secretion a constellation of gastrointestinal symptoms has been consistently observed and reported by clinicians in the past, and treatment of the hypochlorhydria with hydrochloric acid or its substitutes has often been observed to be effective in reducing these symptoms.

Helicobacter (aka Campylobacter) pylori as the major causal factor in chronic hypochlorhydria

Helicobacter (formerly known as Campylobacter) pylori, a recently discovered gastrointestinal bacterial pathogen, has been shown to be etiologic for Type B or antral gastritis, and usually has chronic active pathological changes associated with its presence. Acute Helicobacter infection in most cases induces reduced stomach acid secretion which usually returns to normal levels of secretion after a few months. Yet Helicobacter gastritis has never been known to spontaneously remit after it has been established, and there is evidence suggesting that it often progresses to cause atrophic changes in the gastric mucosa. Since chronic gastritis has been shown in past studies to lead to chronic persistent hypochlorhydria from atrophic damage to secretory tissue, and Helicobacter has been shown to cause most chronic gastritis, the reasonable conclusion is that Helicobacter infection is etiologic for most chronic persistent hypochlorhydria. The apparent exception of the hyperchlorhydria in duodenal ulcer disease associated with Helicobacter infection is explained. The possible clinical relevance of hypochlorhydria will be the subject of a subsequent paper.

Measurement of gastric bicarbonate secretion in the human stomach: different methods produce discordant results.

Human gastric bicarbonate secretion has been measured by back-titration, from pH and pressure of carbon dioxide (PCO2) determinations (using the Henderson-Hasselbalch formula), and from equations based on gastric juice osmolality and [H+] (osmolality-[H+] method). Since these methods show large quantitative differences in their estimations of gastric bicarbonate secretion, we examined each to define the reasons for these discrepancies and establish guidelines for future work in this area. Bicarbonate recovery from 'non-parietal' secretions (0 to 80 mM HCO3) reacting with 'pure parietal secretion' (160 mM HCl) was studied both in vitro and in the pylorus-occluded healthy human stomach during acid suppression, exogenous acidification, and pentagastrin stimulation. The pH/PCO2 method estimated HCO3- accurately under anaerobic conditions in vitro, whereas the osmolality-[H+] method (with correction factors for osmolality incorporated by us) was accurate under aerobic conditions. In the acid-suppressed stomach back-titration was significantly more accurate than the pH/PCO2 method. In the exogenously acidified and pentagastrin-stimulated stomachs the pH/PCO2 method underestimated bicarbonates, and the osmolality-[H+] method was spuriously elevated in the low range and diminished at high bicarbonate concentrations. Estimates of 'basal' bicarbonate secretion (at zero added bicarbonate) were severalfold higher by the osmolality-[H+] method (5.26 +/- 0.33 mmol/h) than by the pH/PCO2 method (1.20 +/- 0.23 mmol/h) or back-titration (0.65 +/- 0.14 mmol/h). In conclusion, gastric bicarbonate was determined most correctly by back-titration in the acid-suppressed stomach, whereas measurement of bicarbonate in the acid-secreting stomach was not accurate with any method.

Stimulation by Capsaicin of Gastric Alkaline Secretion in Anesthetized Rats

Effects of mucosal application of capsaicin on alkaline secretion were examined in the stomachs of anesthetized rats and compared with those in the duodenum. The stomach (acid secretion was inhibited by omeprazole given i.p.) or the duodenum was perfused with saline (pH 4.5); both the pH of the perfusate and transmucosal potential difference (PD) were continuously monitored; and the HCO3− output was determined by the pH change. Under these conditions, the mucosal application of capsaicin (0.3–6 mg/ml for 30 min) caused significantly increased pH and HCO3− output in a concentration-related manner in both tissues, while PD increased in the duodenum and decreased in the stomach. The HCO3− stimulatory action of capsaicin was markedly attenuated by sensory deafferentation, significantly mitigated by prior administration of indomethacin, and exhibited a marked tachyphylaxis after the repeated exposure at a high concentration (6 mg/ml). None of these treatments had any effect on the pH, PD and HCO3− responses induced by prostaglandin E2 (300 μg/kg, i.v.) in these tissues. These results indicate that mucosal application of capsaicin increased the gastroduodenal HCO3− output by stimulation of capsaicin-sensitive sensory neurons. This action may be in part mediated by endogenous prostaglandins.

Histamine and atopic eczema.

Apart from increased production of immunoglobulin E antibodies and disturbed T-cell regulation, altered patterns of releasability of vasoactive mediators have been described in patients with atopic eczema. The best studied substance is histamine which is a classical inducer of pruritus in man. Elevated concentrations of histamine have been found in vivo in the skin and in the plasma of patients with atopic eczema especially during exacerbation of the disease. Similar findings have been described for other atopic diseases as extrinsic bronchial asthma. Histamine acts via characteristic receptors; symptoms as itch, wheal formation, mucus production, contraction of smooth muscle, tachycardia H2-effects include acid secretion in the stomach as well as the development of flush and itch reactions, blood pressure changes and cardiac arrhythmia. Of special interest is an inhibitory effect of histamine on lymphocyte reactions mediated via a H2-receptor. The existence of a new H3-receptor in the brain serving as autocrine feed-back inhibitor of histaminergic neurones has been established in the rat but not yet in man. In vitro an increased histamine releasability of peripheral leukocytes has been found after stimulation with a variety of different substances. The difference between patients with atopic eczema and normals is generally most pronounced after stimulation with anti-IgE. There is, however, a tendency towards an increased spontaneous histamine release compared to normals. The release reaction of histamine seems to occur more rapidly in atopics compared to normals.(ABSTRACT TRUNCATED AT 250 WORDS)

Potential difference responses to nutrient K +, Cl − and Na + changes in secreting and resting states of frog stomach

The effects of changes in nutrient concentrations of K +, Cl − and Na + on the transmucosal potential difference (PD) and the resistance were compared for secreting fundus and resting fundus of Rana pipiens. Increase of K + from 4 to 40 mM, decrease of Cl − from 81 to 8.1 mM and decrease of Na + from 102 to 10 mM gave, 10 min after the change in the secreting fundus, Δ> PD values of −28.2, −19.8 and −7.5 mV , respectively. In the resting fundus with SCN − inhibition, the same changes in nutrient ion concentration gave Δ> PD values of −20.1, −17.0 and −10.2 mV , respectively. Changes in Na + concentration were considered in a set of experiments of high acid secreting stomachs (4 to 6 μequiv. · h −1 · cm −2). Here, Δ> PD gave for 10-fold decreases in Na + concentration in secreting fundus −4.8 mV and in resting fundus with SCN − inhibition −22.6 mV. Omeprazole inhibition gave results quite similar to those with SCN t- inhibition. From these results in going from secretion to inhibition, it follows that the increment of K + conductance if it increased was lower than the increase in NaCl symport conductance since the change in ΔPD for K + decreased and that for Na + increased. Also HCO 3 − conductance increased with inhibition. After SCN − inhibition the transmucosal resistance initially increased and later decreased. The decrease can be accounted for by the increase in conductance of the NaCl symport pathway and of the HCO 3 − pathway.

The role of histamine and serotonin in gastric acid secretion: A comparative study in gastric and duodenal ulcer patients

The inter‐relationship between histamine and serotonin (5HT) levels in gastric juice and their role in stomach acid secretion in gastric (GU) and duodenal ulcer (DU) patients were investigated. DU patients showed a relatively higher basal gastric acid secretion, but had lower histamine and 5HT levels in their gastric juice than those with GU; these amine levels reflected their release from the stomach wall into its lumen. Tetragastrin injection (5 μg/kg, i.m.) increased the gastric secretion of acid and histamine in DU patients; however, the increased release of 5HT into the gastric lumen was not as much as that seen in GU patients. This study suggests that the high basal gastric acid in DU cases is related to hyposecretion of 5HT (a possible physiological inhibitor of gastric acid secretion) in the stomach. Tetragastrin‐induced hypersecretion of gastric acid in DU patients may be due to a higher level of histamine in relation to significantly lower amounts of 5HT secreted from their stomachs. The reverse may apply to the mechanism for the relative hyposecretion of gastric acid in GU patients compared to those with DU.

Sites of resistance changes with inhibition of acid secretion in frog stomach.

The primary purpose of this study was to determine the sites of resistance changes from thiocyanate inhibition of secretion to better evaluate models of the gastric proton pump. The potential difference, resistance, and H+ secretory rate were measured with various tonicities of the secretory fluid. Thiocyanate (SCN) inhibition generally produces a resistance increase, but with nutrient Ba, the resistance is high and SCN decreases it. The latter effect is also seen with cimetidine. In the secreting fundus a hypotonic secretory solution has a small effect on resistance, but in the inhibited fundus the effect is huge, due to increase of resistance of the lumen-tubular cell pathway. With a hypotonic secretory solution, for inhibited fundus (cimetidine or omeprazole) and antrum, SCN does not decrease the resistance of the surface cells and/or the transintercellular pathways with or without Ba. The SCN resistance decrease with Ba is via the tubular cell pathway. With Ba the resistance of the nutrient membrane of the tubular cells decreases after SCN or cimetidine inhibition. The findings further support the concept that under standard conditions the resistance via the lumina and tubular cells is low and that via the surface cells and transintercellular pathways is high.

Stomach acid secretion in submissive and aggressive rats.

These studies were conducted to determine whether aggressive and submissive behavior are related to either an increase or a decrease in gastric secretion. In Experiment 1, intruder rats placed in an established male-female colony and attacked by a dominant alpha male secreted less acid than intruders exposed to nonaggressive males and females. In Experiment 2, intruders exposed to attack and subsequently returned to the encounter site, but protected from physical attack, still demonstrated a gastric hyposecretion. Rats with chronic gastric cannulas in Experiment 3 also revealed an acid inhibition when attacked and later when exposed to, but protected from, attack. Both intruders and attacking males were prepared with gastric cannulas in Experiment 4. Both demonstrated secretory inhibition following attack and attack-protected sessions. The inhibitory effect was greater and more persistent for intruder rats than for aggressive rats. The inhibition occurring during the attack-protected sessions may have been mediated by some conditioning processes. Other associative mechanisms are discussed, and the present results are also compared with those of relevant clinical reports.

Stomach acid secretion in submissive and aggressive rats.

Stomach acid secretion in submissive and aggressive rats.

A guide to the literature on aggressive behavior

A guide to the literature on aggressive behavior

Central regulation of gastric acetylcholine metabolism and acid output

The stress of immobilization in water caused a significant increase in the activity of choline acetyltransferase (CAT) and acetylcholinesterase (AChE), acetylcholine (ACh) content in the stomach and gastric acid secretion, but a decrease of choline content in rats. The increase in CAT activity began 1 h after the application of stress, peaked in 3 h and gradually decreased to normal within 7 h. Similar alterations in gastric acid secretion were observed. The ACh content in stomach tissue increased 30 min after the application of stress and remained elevated for 2.5 h. The content decreased to control levels after 5 h, and significantly increased again after 7 h. The choline content in stomach tissue significantly decreased 1 and 2 h after stress but returned to normal 3 h after the application. An increase in AChE activity was observed 2 and 7 h after the application of stress but normal levels were found after 4 h. Increases in CAT activity and acid output were also observed following administration of 2-deoxy-d-glucose (2-DG), but no changes in ACh and choline contents or AChE activity were observed. The increases in CAT activity and the acid secretion caused by stress and 2-DG administration were blocked by administration of hexamethonium. These results suggest that increases in gastric CAT, AChE activities and ACh content and a decrease of choline content in the early stages are results of increased vagus nerve activity, which influences gastric acid secretion. Furthermore, they suggest that alterations in ACh content and AChE activity at a later stage are less directly related to the increase in vagus nerve activity.

An isolated vascularly perfused stomach for studying drug distribution, metabolism and action in the stomach: acid secretion in response to secretagogues.

Experimental utilization of isolated vascularly perfused rat stomach with retention of the exocrine response to various stimulants was studied. By the inclusion of bovine erythrocytes in the vascular perfusate and by the use of luminal perfusate possessing a suitable buffer capacity, it was found that acid secretion was significantly stimulated by the perfusion of histamine, pilocarpine, cyclic adenosine monophosphate (AMP), dibutyryl cyclic AMP or theophylline. In addition, cimetidine, a histamine H2-receptor antagonist, inhibited histamine-induced acid secretion in a reversible manner. Although tetragastrin stimulated acid secretion in immature rat or guinea pig stomach, it caused little secretory response in adult rat stomach. On the addition of pepstatin, a pepsin inhibitor, to the vascular perfusate, an acid secretion induced by tetragastrin in adult rat stomach was observed. These findings indicate that some changes in gastrin receptors may develop during the maturation process and that gastrin-induced acid secretion is easily altered by peptic activity in the gastric glands of the perfused stomach. The proposed perfusion system should be useful for studying drug distribution, metabolism and action in the stomach.

Acid secretion in fetal rat stomach in vitro.

In vivo fetal rat stomach produces HCl 48 h before birth. This study examines the mechanisms of H+ secretion from days 19 to 21 before birth. Isolated fetal stomachs were mounted as flat sheets in Ussing chambers for measurement of the transepithelial H+ fluxes (JH+) and short-circuit current (Isc), as indexes of the active ionic fluxes, and for measurement of total ionic conductance (G) and unidirectional mannitol fluxes from serosa to mucosa (JMans leads to m), as indexes of passive permeability. The results indicate that JH+ was absent at day 19 but reached 0.75 +/- 0.1 and 0.75 +/- 0.09 mueq . h-1 . cm-2 at days 20 and 21, respectively. Concomitantly, Isc increased significantly (56%) between days 19 and 20 in the direction of anion secretion or cation absorption. Parallel reductions in G (45%) and in JMans leads to m (66%) were observed between days 19 and 20. In conclusion, the simultaneous appearance of active H+ secretion and decreased passive transepithelial permeability strongly suggests that both processes are involved in the mechanism of acidification of the fetal rat stomach before birth.

The effcts of sodium fluoride on gastric acid and electrolyte output in the anaesthetized cat.

1. The possibility of a Na+/H+ exchange mechanism in the presence of NaF (Bond & Hunt, 1956) has been studied in acid secreting and non-acid secreting stomachs of anaesthetized cats. 2. In non-acid secreting stomachs, although H+ loss and Na+ gain were both pH related, there was no constant relationship between the two. 3. The H+ loss in non-acid secreting stomachs could not account for the H+ loss in histamine stimulated stomachs. 4. In acid secreting stomachs the Na+ or neutral Cl- gain was only of the order of 50% of the H+ loss, and, in the presence of isosmolal NaNO3, NaF produced the same reduction in H+ but with a markedly suppressed gain in neutral chloride. 5. The NaF induced reduction in H+ output was accompanied by reductions in the total Cl- output, the K+ output and the mucosal blood flow. 6. It is concluded that the reduction in H+ output from histamine stimulated stomachs is largely a result of inhibition of secretion.

Regular and irregular cycles of interdigestive contractions in the stomach.

We have previously reported that during the interdigestive state repeated episodes of high-amplitude contractions interrupted by long-lasting motor quiescence were seen to occur regularly until the next meal in the dog. However, none of the dogs used in our laboratory showed such regular changes in gastric motor pattern all the time during the interdigestive state. In the present study, we measured plasma motilin concentrations and intraduodenal pH together with gastric motor activity in conscious dogs. It was found that as long as intraduodenal pH remained between 7.0 and 8.5 the regular occurrence of the interdigestive contractions was closely associated with increases in the plasma immunoreactive motilin (IRM) concentration. However, when intraduodenal pH became acid, there were no typical interdigestive contractions even though plasma IRM concentration was elevated. We consider that high-amplitude contractions like the interdigestive contractions could not be evoked in the acid-secreting stomach even if the plasma IRM concentration was elevated during the interdigestive state. Acid secretion during the fasted state, the cause of which is not known, seems to be one of the main factors in disturbing the regularity of the interdigestive motor pattern.

Investigation of the role of extracellular calcium in the control of acid secretion in the isolated whole stomach of the rat.

1 An isolated stomach preparation from immature rats has been used to study the role of extracellular calcium in the control of gastric acid secretion. Calcium was removed from both the serosal and mucosal solutions either in the absence of a chelating agent or in the presence of EGTA.2 Removal of calcium in the absence of EGTA had no significant effect on basal acid secretion or the acid responses to gastrin and dibutyryl cyclic adenosine 3',5'-monophosphate (db cyclic AMP). Under the same conditions there was a marked potentiation of the acid response to histamine, and a reduction of the acid response to acetylcholine which was readily reversed on restoring calcium to the bathing solutions.3 Removal of calcium in the presence of EGTA caused an inhibition of basal acid secretion and of the acid responses to histamine and db cyclic AMP. In each case this reduction in acid output was readily reversed on bathing the stomachs in normal calcium-containing (2.5 mM Ca(2+)) EGTA-free solutions.4 The inhibition of the acid response to histamine produced by Ca(2+)-free solutions which contained EGTA was not reversed on bathing the stomachs in solutions that contained both EGTA (0.1 mM) and an excess of calcium (2.5 mM).5 The removal of extracellular calcium in the absence of EGTA provided evidence that the secretion of H(+) ions is dependent under some conditions on calcium ions. The possibility cannot be excluded that EGTA itself exerts an inhibitory influence on the process of acid secretion.

CHOLERA, NON-VIBRIO CHOLERA, AND STOMACH ACID

Fasting and postprandial stomach acid production were low in 16 of 37 Bangalees convalescing from cholera or non-vibrio cholera. Gastric juice of hypochlorhydric patients did not kill cholera vibrios in vitro, whereas that from normochlorhydric patients rapidly killed vibrios in concentrations up to 10 10/ml. To determine whether hypoacidity resulted from cholera or was a common predisposing factor, basal and betazole-hydrochloride-stimulated acid production were measured before and after cholera in a second group of patients consisting of American volunteers participating in a vaccine development programme. Cholera did not alter the stomach acid secretion of American volunteers, but low precholera basal acid production predisposed to severe cholera. The results indicate that hypochlorhydria observed in convalescent Bangalee cholera patients is not caused by cholera, and must therefore have preceded it. Idiopathic tropical hypochlorhydria may be a major factor accounting for the high incidence of diarrhœa due to acid-sensitive pathogens in developing countries.

Chloride Transport and Acid Secretion in Stomach

Chloride transport in isolated frog gastric mucosa is known to include major components due to active transport and exchange diffusion, and a minor component due to passive diffusion, but the sites responsible for moving Cl- within the mucosa have not been identified. The present study shows that the method used by Zerahn and others to measure transport pool yields an apparent Cl- pool which is close to the Cl- content of mucosal cells measured by chemical or radioactive means. Uptake of Cl- by the mucosal cells across the luminal surface in 2 min is rapid, constituting over one-half of the steady state cell content. The results suggest that much of this uptake occurs by exchange diffusion of Cl- at the secretory surface.

Response contingency and human gastric acidity.

ABSTRACTThe purpose of this study was to investigate the relationship between avoidance behavior of human subjects and gastric acid changes. An intragastric radio transmitter was employed to record stomach acid secretion rates. The subjects were divided into two groups. The members of the Response‐Contingent (RC) group were led to believe that they would be able to avoid a strong electric shock during the Test phase of their session. In the No‐Response (NR) group, subjects were correctly told that they would be without means of avoiding shock. The results demonstrated that (a) subjects could not be differentiated according to gastric acid secretion rate strictly on the basis of whether or not they made an avoidance response to an aversive stimulus; (b) a non‐significant majority of subjects in both groups exhibited decreased gastric acid secretion rates during the Test phase; and (c) both groups showed a significantly faster rate of gastric acid secretion during the Post‐Test phase than during the Test condition.