Measurement Of Gastric Acid Secretion Research Articles

Non-invasive method for the assessment of gastric acid secretion.

Methods for the measure of gastric acid secretion include invasive and non-invasive tests. The gold-standard to measure the acid output is the collection of gastric after in basal condition (Basal Acid Output, B.A.O.) and after an i.m. injection of pentagastrin (Maximal Acid Output, M.A.O.). However, direct measurement of gastric acid production is out of order in clinical practice, but many GI symptoms are claimed to be related with acid disorders and empirically cured. Hypochlorhydria is associated with precancerous conditions such as chronic atrophic gastritis (CAG). Acid measurement with non-invasive methods (pepsinogens) is supported by international guidelines. (www.actabiomedica.it)

79-Year-Old Woman With Forgetfulness

79-Year-Old Woman With Forgetfulness

Measurement of Gastric Acid Secretion in the Anaesthetized Rat

The protocols described in this unit are designed to assess the effects of substances on gastric acid secretion by the rat stomach, with the animal under general anesthesia. Both stimulatory and inhibitory effects of compounds can be evaluated and specific mechanisms of action can also be investigated. Acid secretion is induced by substances that directly activate parietal cell receptors (histamine and bethanechol), by indirect stimuli, like 2-deoxy-D-glucose, by electrical stimulation of vagal nerves, or by the peptide pentagastrin. Reference antisecretory drugs are represented by histamine H(2) receptor antagonists and proton pump inhibitors. This model allows the evaluation of complete dose-response curves together with a time-course of the secretory/antisecretory effects. Indirect effects involving activation or inhibition of vagal pathways are evaluated in intact animals by means of electrical vagal stimulation or in vagotomized animals.

Inhibition of Pentagastrin-Stimulated Gastric Acid Secretion by Pantoprazole and Omeprazole in Healthy Adults

Our objective was to compare the onset and duration of a single dose of pantoprazole or omeprazole on maximally stimulated gastric acid secretion. This double-blind, randomized, placebo-controlled study involved 36 healthy adults and utilized continuous pentagastrin infusion to stimulate acid secretion after administration of pantoprazole, 40 mg, omeprazole, 20 mg, or placebo. Gastric aspirates were collected over 24 hr and analyzed for volume, pH, and hydrogen ion concentration, and gastric acid outputs (GAO) were calculated. Comparison between GAO and intragastric pH was performed. Pantoprazole resulted in significantly greater inhibition of GAO than omeprazole. Mean cumulative 24-hr GAO was 164 +/- 130 mEq for pantoprazole versus 283 +/- 159 mEq for omeprazole (P = 0.031). Pantoprazole patients reached and maintained GAO levels below the 10-mEq/hr threshold at 5.7 hr, whereas omeprazole patients never reached this threshold. We conclude that pantoprazole significantly suppressed gastric acid secretion compared to omeprazole. Comparisons between pH and GAO showed that GAO was a more appropriate measure of gastric acid secretion than intragastric pH.

Observations of gastric mucosal blood flow using 99Tcm in rat and man.

The 99Tcm clearance technique is shown to be a useful method of assessing gastric function. It is easily carried out and is relatively non-toxic--the dose of isotope could be reduced to 100 muCi or less without sacrificing the accuracy of the investigation. Although the results are preliminary and the number of cases investigated so far is small, they suggest that the measurement of pertechnetate clearance is directly related to gastric mucosal blood flow; it is a useful parameter of gastric function and may well prove to be a more accurate discriminant in cases of peptic ulceration than the conventional measurement of gastric acid secretion.

The Effect of Intragastric Ammonia Production on Titratable Gastric Acid Output in Helicobacter pylori-Infected Patients with Chronic Gastritis

The purpose of this study was to assess whether intragastric neutralization of HCl by ammonia in Helicobacter pylori-infected patients could meaningfully affect the titratable acid output as a measure of gastric acid secretion in a relation to the severity of infection. In 79 patients with different degrees of Helicobacter pylori infection and chronic gastritis, the basal acid output (BAO) and maximal acid output (MAO) after pentagastrin (6 microg/kg s.c.) was estimated. Cl- and NH4+ contents in these fractions were also assayed. H+/Cl- ratio in the MAO fraction was diminished in markedly infected patients (68.1 +/- 3.9%, vs 84.1 +/- 3.3% in noninfected patients; P < 0.005). Ammonium content was maximal in patients with marked infection (0.912 +/- 0.086 vs 0.149 +/- 0.034 mmol/hr in MAO [P < 0.001] and 0.475 +/- 0.063 vs 0.105 +/- 0.016 mmol/hr in BAO of noninfected patients [P < 0.001]), with intermediate values in mild and moderate infection. The NH4 +/(H+ + NH4+) ratio reached 27.01 +/- 7.34% in the BAO of moderately infected patients, vs 10.22 +/- 3.81% in noninfected patients (P = 0.05), and 7.25 +/- 1.06% in the MAO of markedly infected patients, vs 1.14 +/- 0.33% in noninfected patients (P < 0.001). The intragastric ammonia production affects the titratable acid output in Helicobacter pylori-infected patients dependent on the severity of infection. Therefore this factor should be taken into consideration in the evaluation of gastric secretory function in Helicobacter pylori-infected patients.

Serum pepsinogen concentrations as a measure of gastric acid secretion in Helicobacter pylori-negative and -positive Japanese subjects

Although previous studies have indicated that serum pepsinogen I levels, as well as the pepsinogen I/II ratio, were positively correlated with maximal gastric output, the relationship may be different between Helicobacter pylori-negative and -positive subjects. The aim of this study was to investigate the relation between serum pepsinogen concentrations and gastric acid secretion in H. pylori-positive and -negative subjects separately. The presence of H. pylori infection, the serum pepsinogen concentrations, and gastric acid secretion were investigated in 182 subjects without localized lesions in the upper gastrointestinal tract. Serum pepsinogen concentration was measured by radioimmunoassay, and maximal gastric acid output was estimated by an endoscopic gastrin test, as we have previously shown. In H. pylori-positive subjects, serum pepsinogen I levels and the pepsinogen I/II ratio were significantly correlated with gastric acid secretion, although the latter showed a better correlation (r=0.40 and 0.53, respectively). On the other hand, in H. pylori-negative subjects, serum pepsinogen concentrations were well correlated with acid secretion (r=0.57), but there was no relation between the pepsinogen I/II ratio and acid secretion. The correlations between serum pepsinogens and gastric acid secretion differ, depending on the presence or absence of H. pylori infection. With the use of serum pepsinogens as a simple measure of gastric acid secretion, therefore, consideration of H. pylori infection status is needed. Because the determination of the acid secretory level has some clinical implications in both H. pylori-positive and -negative subjects, its estimation by serum pepsinogen concentrations can be of practical use.

Gastric pH above 2.5 is of limited use as a measure of acid inhibition

Purpose: Acid in the gastric refluxate is a key contributor to mucosal injury in GERD. Hence, quantification of gastric acid secretion is a logical measure of efficacy of medical therapy for GERD. Gastric acid output (GAO = [H+] gastric volume) measures actual gastric acid secretion. However, intragastric pH is frequently used to assess the efficacy of proton pump inhibitor therapy. The purpose of this study was to assess the accuracy of intragastric pH as a measure of gastric acid secretion and potential esophageal acid load.

Effect of suramin on ethanol-induced gastric mucosal injury: Relationship between tissue distribution and severity of damage

Suramin exerts antitumour effects by interfering with the biological activity of several growth factors. It is also known that growth factors, including epidermal growth factor, play a primary role in the protection of gastric mucosa and promotion of ulcer healing. In the present study, the penetration of suramin into the stomach as well as the influence exerted by this drug on ethanol-induced gastric mucosal damage were investigated. Suramin was administered by the intraperitoneal route to male rats every other day for fourteen days. Animals were then used for: 1. Assessment of suramin levels in plasma and tissues 2. Histomorphometric evaluation of ethanol-induced gastric mucosal damage 3. Measurement of gastric acid secretion after pylorus ligation.

Modulation of pentagastrin-induced histamine release by histamine H3 receptors in the dog.

The histamine H3 receptor has been shown to inhibit pentagastrin-induced gastric acid secretion in dogs. Since pentagastrin releases histamine in dogs, we have now assessed whether the effects of H3-receptor ligands may be indirectly mediated by changes in gastric histamine release. Pentagastrin infusions (1 or 6 micrograms/kg/h), alone or together with the H3-receptor agonist (R) alpha-methylhistamine (1.2 mumol/kg/h) or the antagonist thioperamide (0.1 mumol/kg/h), were performed in dogs. One group (anaesthetized) was used for enzyme immunoassays of plasma histamine and, when required. (R) alpha-methylhistamine in the gastrosplenic vein, and another group (non-anaesthetized) for measurement of gastric acid secretion. Histamine levels were increased five- and eight-fold after 1 and 6 micrograms/kg/h pentagastrin, respectively, whereas acid output was nearly maximal at the lower dosage. (R) alpha-methylhistamine, at a plasma concentration of 0.15 microM, inhibited histamine release by 78% (P < 0.007) and 37% (not significant) and the total acid output by 44% (P < 0.05) and 19% (not significant) after infusion of 1 and 6 micrograms/kg/h pentagastrin, respectively. Thioperamide, together with pentagastrin in low dose, significantly increased histamine release by 212% (P < 0.05), whereas acid output increased by 34% (not significant). The histamine H3 receptor mediates a negative feedback control of pentagastrin-induced release of gastric histamine. It is tonically activated by endogenous histamine after pentagastrin in low dosage. The control of acid secretion by the H3 receptor seems to involve modulation of endogenous histamine release, possibly by means of enterochromaffin-like cells.

Measurement of gastric acid secretion by a novel noninvasive test: [formula omitted], D. Mahalanabis, P.K. Bardhan, N.H. Alam, R. Zaman, S. Islam, K. Gyr. International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh and Dept. of Gastroenterology, Basle University, Switzerland

Measurement of gastric acid secretion by a novel noninvasive test: [formula omitted], D. Mahalanabis, P.K. Bardhan, N.H. Alam, R. Zaman, S. Islam, K. Gyr. International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh and Dept. of Gastroenterology, Basle University, Switzerland

Postprandial alkaline tide: does it exist?

The concept of an alkaline tide which compensates for gastric acid secretion suggests the possibility of indirect measurement of gastric acid secretion. This study was designed to determine whether postprandial changes in renal and respiratory function could be used to assess gastric secretion in healthy adults. Volunteers ate one of three standard (low, medium or high protein) breakfasts on separate days. A fall in urine acid output was observed during 2 h after the high protein meal, but not after the medium or low protein meal. Fasting subjects showed a similar fall in urine acid output over a 2-hour period. Pretreatment with ranitidine 150 mg b.i.d. had no effect on basal or postprandial urine acid output. We conclude that changes in urine acid output are not related to the gastric secretory response to food. In a separate study, treatment with omeprazole 20 mg daily had no effect on postprandial respiratory function (minute ventilation; mixed expired CO2; minute volume of CO2; respiratory exchange ratio; venous blood pH, pCO2 or bicarbonate; and end tidal CO2). Thus we were unable to detect a respiratory alkaline tide after a standard breakfast. These findings suggest that any respiratory or urinary compensation for gastric acid secretion is too small to be of physiological or clinical significance.

New non-invasive test of gastric acid secretion for use in children.

Loss of the gastric acid barrier may lead to recurrent enteric infections, small intestinal bacterial overgrowth, persistent diarrhoea, and thus malnutrition. To investigate this possibility, a new, non-invasive test of gastric acid secretion was developed ideal for field use in the developing world, where chronic diarrhoea and undernutrition are common. The test relies on the capacity of the kidney to retain H+ during gastric acid secretion, leading to a post-prandial urine 'alkaline tide'. Gastric intubation studies of seven healthy adult volunteers showed a direct relation between changes in gastric acid secretion and changes in urine acid output (measured as the H+/creatinine molar ratio in spot urine samples). Subjects who secreted gastric acid in response to stimulation with a sham feed showed a fall in urine acid output > 0.5 mmol H+/mmol creatinine (range -7.4 to -1.52 mean -1.12). The most reproducible decrease in urine acid output in response to normal food was observed around the time breakfast was usually eaten and was abolished by 36 hours of treatment with ranitidine. Breakfast time reductions in postprandial urine acid output in 22 healthy English children were comparable with those in healthy adults, and significantly different from values in achlorhydric adults. They were much more variable, however, in 106 Gambian children in whom values spanned both normochlorhydric and achlorhydric ranges (-12.7 to +1.8). Measuring changes in urine acid output at breakfast time provides a reliable indirect measure of gastric acid secretion that can be used in field conditions, enabling the relation between gastric acid output and the development of diarrhoeal diseases to be investigated.

Continuous gastric pH monitoring in children: The effect of gastric emptying on the measurement of gastric acid secretion

Continuous gastric pH monitoring offers the opportunity to evaluate gastric acid secretion in humans without the need for collection of gastric aspirates. However, gastric emptying may be an important variable for the accurate measurement of gastric acid secretion using continuous gastric pH monitoring. We conducted an in vitro study (phase I) to evaluate the effect of gastric emptying on gastric pH. The in vitro study used a laboratory model in which continuous pH monitoring of a standard formula (Nutramigen, 100 mL) in a reservoir was performed while varying both the reservoir emptying rate (10% to 80%) over 1 hour and the amount of added acid (2 to 15 mEq/h: in vivo equivalent of 6 to 45 mEq/m2 BSA/h). An in vivo study (phase II) was then performed in 28 infants less than 6 months of age who had gastroesophageal reflux (GER) documented by 18- to 24-hour esophageal pH monitoring. At the end of esophageal pH monitoring, the pH electrode was advanced into the stomach for measurement of gastric pH continuously for 2 hours after a feeding of Nutramigen formula (300 mL/m2 BSA). Each patient also had a radionuclide gastric emptying study performed with the same volume of Nutramigen formula. In the in vitro model, the reservoir pH (% time pH less than 4) was proportional to the reservoir emptying rate only when acid was added at less than 15 mEq/h (less than 45 mEq/m2 BSA/h). Reservoir pH was independent of reservoir emptying rate when acid was added at 15 mEq/h (45 mEq/m2 BSA/h).(ABSTRACT TRUNCATED AT 250 WORDS)

Intrahypothalamic microinfusion of corticotropin-releasing factor inhibits gastric acid secretion but increases secretion volume in rats

Bilateral microinfusion of synthetic ovine corticotropin releasing factor (oCRF; 0–4.0 μg/rat [0–856 pmol/rat]) into the paraventricular nucleus or the ventromedial nucleus of the rat hypothalamus inhibited gastric acid secretion in a dose-related manner. Unexpectedly, these microinfusions both decreased acid concentration and increased secretion volume; total acid output (acid concentration multiplied by secretion volume) was strongly inhibited. In the lateral hypothalamus, CRF microinfusion also both decreased acid concentration and increased secretion volume, but total acid output did not change. oCRF microinfusion into the caudate-putamen did not significantly affect any measure of gastric acid secretion even at the highest dose used. The increased secretion volume seen after oCRF microinfusion is unique; all other centrally acting inhibitors of gastric acid secretion decrease secretion volume. It is possible that hypothalamic CRF may influence gastric secretory function.

Effect of vagotomy and glucose administration on gastric acid secretion in the Atlantic cod, Gadus morhua.

Cods were prepared for measurement of gastric acid secretion. Cannulae were implanted for drainage of the stomach and for separate perfusion of the stomach and intestine. Fishes, intestinally perfused with diluted sea-water (33% SW) exhibited high rates of acid secretion. This "basal" secretion was abolished (96% inhibition) by bilateral vagotomy. Perfusion of the stomach with isosmotic glucose (5.5%) diminished the amount of titratable acid in the gastric effluence, and induced oral ingestion of water. Only part of the decrease could be explained by neutralization by ingested sea-water. Perfusion of the intestine with 5.5% glucose, containing sea-water to raise the osmolality to that of 50% SW, depressed gastric acid secretion compared to 50% SW-perfused controls, without significantly affecting oral intake of water. I.m. administration of glucose, increasing plasma glucose to the same level as intraluminal administration, did not affect acid secretion or oral water ingestion. The study demonstrates the existence of a potential intestinal mechanism for inhibition of gastric acid secretion, and indicates that vagal activity is independent of the blood glucose level in the cod.

Measurement of gastric acid secretion in isolated gastric mucosa of the rat: effects of secretagogues and inhibitors including cyclic adenosine monophosphate related agents and an H2-receptor antagonist.

An improved method was described for the measurement of gastric acid secretion of isolated rat gastric mucosa. With this method, dose-dependent acid secretory responses were obtained to secretagogues such as histamine, bethanechol, tetragastrin and dibutyryl cyclic adenosine monophophate (AMP). However, the maximum response to tetragastrin was always smaller than that to the other secretagogues in this preparation. Inhibitory effects on acid secretion of some antisecretory agents were also examined. Antagonistic interactions of atropine against bethanechol, and of metiamide against histamine were clearly confirmed. On the other hand, inhibitions of metiamide on bethanechol and of atropine on tetragastrin or histamine were found rather weak in contrast to the results obtained with other methods. Strong stimulatory effect of theophylline and absence of the influence of dibutyryl cyclic GMP were shown in our preparation. The actions of miscellaneous agents including prostaglandin E1, imidazole and metabolic inhibitors were also described.

Measurement of gastric acid secretion by conductivity

Gastric acid secretion in the anaesthetized rat has been measured by continuously recording the conductivity of the effluent in the reperfusion system previously developed by the authors. (H +) and (Na +) were measured by titration and flame photometry respectively and compared with the total conductivity of the effluent. The differences between the calculated and measured conductance were within the experimental error of the observations. There was no clear relationship between rates of secretion of hydrogen ions and sodium ions in this preparation. Conductance was used to measure acid concentration and to assay inhibitors and stimulants of gastric acid secretion. A conductivity meter has been designed and used to measure gastric acid secretion in the perfused rat stomach preparation. Measurements of conductivity were shown to be a measure of the hydrogen ion concentration of the effluent. The quality and linearity of the response was superior to that achieved with pH methods. The sensitivity of the system has been increased which has enabled 10 ng of gastrin I to give a significant effect. It was possible to monitor six preparations with one meter during assays of urogastrone and gastrin.

Measurement of gastric acid secretion in the rat by test meal: effects of distension, pentagastrin and propantheline.

Accuracy of a modified test meal technic was assessed by measurement of gastric acid secretion and emptying in male Wistar rats under various conditions. Secretion was higher when a 10% dextrose solution was given during fasting, than when only water was allowed. A 48-hour fast with 10% dextrose solution ad libitum was optimal. The coefficients of variation, for acid output and gastric emptying obtained by duplicate tests under resting conditions, ranged from 18 to 30%. Oral propantheline bromide inhibited acid secretion. The degree of inhibition was similar for measurements by test meal and after pyloric ligation. Pentagastrin produced a highly significant increase in acid secretion. The dose required to evoke a maximal response is considerably higher in the rat than in man. Serial measurements, with test meal volumes of 5, 7.5 and 10 ml, and with graded doses of pentagastrin, revealed no relationship between gastric acid secretion and test meal volume. Hence, distension may be physiologically unimportant in the control of gastric secretion in this species; assessment of secretion by test meal does not require that test meal volume be regulated accurately according to the size of the rat. Incomplete emptying of the stomach, and failure to recover all marker (phenol red) at the end of the test period, result in overestimation of gastric emptying and, to a lesser extent, of acid secretion. The significance of these errors can be minimized by the use of a large volume test meal.