Hypochlorhydria Abstracts 12


Acid suppressive drugs and gastric cancer: a meta-analysis of observational studies.
            (Ahn et al., 2013) Download
AIM:  To evaluate the association between acid suppressive drug use and the development of gastric cancer. METHODS:  A systematic search of relevant studies that were published through June 2012 was conducted using the MEDLINE (PubMed), EMBASE, and Cochrane Library databases. The search included observational studies on the use of histamine 2-receptor antagonists (H₂RAs) or proton pump inhibitors and the associated risk of gastric cancer, which was measured using the adjusted odds ratio (OR) or the relative risk and 95%CI. An independent extraction was performed by two of the authors, and a consensus was reached. RESULTS:  Of 4595 screened articles, 11 observational studies (n = 94558) with 5980 gastric cancer patients were included in the final analyses. When all the studies were pooled, acid suppressive drug use was associated with an increased risk of gastric cancer risk (adjusted OR = 1.42; 95%CI: 1.29-1.56, I² = 48.9%, P = 0.034). The overall risk of gastric cancer increased among H₂RA users (adjusted OR = 1.40; 95%CI: 1.24-1.59, I² = 59.5%, P = 0.008) and PPI users (adjusted OR = 1.39; 95%CI: 1.19-1.64, I² = 0.0%, P = 0.377). CONCLUSION:  Acid suppressive drugs are associated with an increased risk of gastric cancer. Further studies are needed to test the effect of acid suppressive drugs on gastric cancer.

The Evolution of Stomach Acidity and Its Relevance to the Human Microbiome.
            (Beasley et al., 2015) Download
Gastric acidity is likely a key factor shaping the diversity and composition of microbial communities found in the vertebrate gut. We conducted a systematic review to test the hypothesis that a key role of the vertebrate stomach is to maintain the gut microbial community by filtering out novel microbial taxa before they pass into the intestines. We propose that species feeding either on carrion or on organisms that are close phylogenetic relatives should require the most restrictive filter (measured as high stomach acidity) as protection from foreign microbes. Conversely, species feeding on a lower trophic level or on food that is distantly related to them (e.g. herbivores) should require the least restrictive filter, as the risk of pathogen exposure is lower. Comparisons of stomach acidity across trophic groups in mammal and bird taxa show that scavengers and carnivores have significantly higher stomach acidities compared to herbivores or carnivores feeding on phylogenetically distant prey such as insects or fish. In addition, we find when stomach acidity varies within species either naturally (with age) or in treatments such as bariatric surgery, the effects on gut bacterial pathogens and communities are in line with our hypothesis that the stomach acts as an ecological filter. Together these results highlight the importance of including measurements of gastric pH when investigating gut microbial dynamics within and across species.

The Hypochorhydria of Asthma in Children
            (Bray, 1931) Download
80% of asthmatic children have a deficiency of gastric acid secretion compared with normal children.

Tubeless gastric analysis with azure A and maximal histamine stimulation.
            (Correia and de Moura, 1963) Download

Gastric secretion of acid and intrinsic factor in patients with hyper- and hypothyroidism
(Dotevall and Walan, 1969) Download
Fifteen consecutive thyroid disease patients, ten with hyperthyroidism and five with hypothyroidism, have been investigated as far as gastric secretion was concerned. Gastric secretion of acid and intrinsic factor was studied in the patients both basally and with the augmented histamine test. In eight patients with hyperthyroidism and all patients with hypothyroidism, the gastric secretion of acid after histamine stimulation was significantly lowered. The secretion of intrinsic factor correlated with the secretion of acid, and was significantly depressed in four patients with hyperthyroidism and three with hypothyroidism. Further studies showed pernicious anemia in two patients with hypothyroidism.

Endoscopic findings for predicting gastric acid secretion status.
            (Hatta et al., 2014) Download
BACKGROUND AND AIM: Gastric acidic abnormalities are related to various types of diseases in Helicobacter pylori (H. pylori) infection status. However, no studies have shown correlations between many tiny endoscopic findings and the acid secretion level simultaneously. In the present study, we investigated predictive tiny endoscopic findings of hyperchlorhydria and hypochlorhydria. METHODS: A total of 223 subjects without organic diseases who underwent esophagogastroduodenoscopy and endoscopic gastrin test (EGT) for estimating gastrin-stimulated gastric acid secretory response between 1999 and 2012 at our institution were retrospectively analyzed. Two blinded expert endoscopists reviewed the images independently and recorded the endoscopic findings. RESULTS: According to the EGT values, the enrolled subjects were categorized into hyperchlorhydria, normal acid secretion, and hypochlorhydria groups. In all subjects, hematin (odds ratio [95% confidence interval] = 3.32 [1.40-7.84]) and antral erosion(2.88 [1.24-6.70]) were the predictive endoscopic findings for hyperchlorhydria, and swelling of areae gastricae (14.4 [5.74-36.1]) and open-type atrophy (15.1 [7.35-31.1]) were those for hypochlorhydria. In addition, the predictive endoscopic findings for hyperchlorhydria differed according to the H. pylori infection status, hematin in H. pylori-positive subjects and antral erosion in H. pylori-negative subjects, in contrast to those for hypochlorhydria, which were the same irrespective of the H. pylori infection status. CONCLUSIONS: We could predict the acid secretion status based on the endoscopic findings regardless of H. pylori infection status, which would be of some help for evaluating the risk for acid-related diseases.

Gastric hypochlorhydria is associated with an exacerbation of dyspeptic symptoms in female patients.
            (Iwai et al., 2013) Download
BACKGROUND:  Gender and gastric acid have been suggested to be independently involved in the pathophysiology of functional dyspepsia, but the interrelationship among gender, dyspeptic symptoms, and gastric acid secretion remains to be evaluated. We sought to explore this issue in dyspeptic patients. METHODS:  A total of 89 outpatients (male, 36; mean age, 55.6 years) with dyspeptic symptoms were analyzed. The degree of dyspeptic symptoms was evaluated and scored using a symptom questionnaire consisting of 3 subcategories: dysmotility-related symptoms, reflux-related symptoms, and epigastric pain-related symptoms. Stimulated gastric acid secretion was directly measured using an endoscopic gastrin test. RESULTS:  The total symptom scores and the epigastric pain-related symptom scores were significantly higher in female patients than in male patients. The dysmotility-related and reflux-related symptom scores were also higher, but not significantly, in the female patients. Multiple regression analysis of age, gender, habitual drinking, smoking, Helicobacter pylori infection, and gastric acid secretion revealed that gender and gastric hypochlorhydria, defined as less than 2.1 mEq/10 min in the endoscopic gastrin test, were significantly associated with higher dyspeptic symptom scores. The total scores and the dysmotility-related scores were significantly higher in the patients with gastric hypochlorhydria than in those with gastric non-hypochlorhydria, and this difference was found to be present only in females. CONCLUSIONS:  Gastric hypochlorhydria in female dyspeptic patients may be involved in the exacerbation of dyspeptic symptoms. Differences in the responsiveness to gastric hypochlorhydria between males and females may be partly responsible for the gender differences in the prevalence and severity of dyspeptic symptoms.

The intriguing relationship of Helicobacter pylori infection and acid secretion in peptic ulcer disease and gastric cancer.
            (Malfertheiner, 2011) Download
Helicobacter pylori infection induces chronic inflammation of the gastric mucosa and thus profoundly affects gastric physiology. In the acute phase of infection, gastric acid secretion is transiently impaired. The morphological damage of the gastric mucosa, changes in gastric hormone release, and disruption of neural pathways all contribute to influence gastric acid secretion in a distinct manner. Changes in gastric acid secretion, whether impaired or increased, are intimately related with the topographic phenotypes of gastritis and the presence of atrophy or absence of corpus atrophy. The interplay of gastritis phenotype and acid secretion are key determinants in disease outcomes. Corpus-predominant gastritis and corpus atrophy are accompanied by hypochlorhydria and carry the highest risk for gastric cancer, whereas antrum-predominant gastritis with little involvement of the corpus-fundic mucosa is associated with hyperchlorhydria and predisposes to duodenal ulcer disease.

Intragastric nitrites, nitrosamines, and bacterial overgrowth during cimetidine treatment.
            (Stockbrugger et al., 1982) Download
A six week course of cimetidine (1 g/day) healed peptic ulcers in 20 of 23 patients (14 with duodenal ulcer, nine with gastric ulcer). Reduction of basal acid output by 73% and peak acid output by 36% led to a rise in concentrations of intragastric aerobic bacteria and nitrate-reducing bacteria. While the mean intragastric concentration of nitrate was unchanged by treatment, there were statistically significant rises in nitrite and N-nitrosamine concentrations. The conversion from nitrates to nitrites was closely related to the occurrence of nitrate-reducing bacteria. In three patients the intragastric milieu had returned to normal two months after cimetidine treatment had been discontinued. Mean nitrite and N-nitrosamine concentrations did not return to pre-treatment levels in the group of eight patients who remained on maintenance cimetidine (0.4 g at night-time) for three months after the full dose treatment. This study shows that cimetidine treatment can create an intragastric milieu resembling that of atrophic gastritis. Large scale and long-term studies are necessary to establish whether these findings have any clinical significance.


Sonic hedgehog: a link between inflammation, gastric atrophy, and acid suppression
            (Van Dop and Van Den Brink, 2010) Download
H secretion is required for expression and processing of Shh. Autocrine or paracrine signaling by Shh is in turn required for full functional differentiation and acid secretion of the parietal cell. Loss of Shh results in loss of acidity, diminished production of somatostatin, and a resulting raise in serum gastrin levels. Interleukin-1 has known negative effects on acid secretion and positive effects in gastrin secretion, but is now shown to also down-regulate Shh which may contribute to the loss of the parietal cells capacity to secrete hydrochloric acid.

Loss of parietal cell expression of Sonic hedgehog induces hypergastrinemia and hyperproliferation of surface mucous cells.
            (Xiao et al., 2010) Download
BACKGROUND & AIMS:  Sonic Hedgehog (Shh) is expressed in the adult stomach, but its role as a gastric morphogen is unclear. We sought to identify mechanisms by which Shh might regulate gastric epithelial cell function and differentiation. METHODS:  Mice with a parietal cell-specific deletion of Shh (HKCre/Shh(KO)) were created. Gastric morphology and function were studied in control and HKCre/Shh(KO) mice between 1 and 8 months of age. RESULTS:  In contrast to control mice, HKCre/Shh(KO) mice developed gastric hypochlorhydria, hypergastrinemia, and a phenotype that resembled foveolar hyperplasia. The fundic mucosa of HKCre/Shh(KO) mice had an expanded surface pit cell lineage that was documented by increased incorporation of bromodeoxyuridine and was attributed to the hypergastrinemia. Compared with controls, numbers of total mucous neck and zymogen cells were significantly decreased in stomachs of HKCre/Shh(KO) mice. In addition, zymogen and neck cell markers were coexpressed in the same cell populations, indicating disrupted differentiation of the zymogen cell lineage from the mucous neck cells in the stomachs of HKCre/Shh(KO) mice. Laser capture microdissection of the surface epithelium, followed by quantitative reverse-transcription polymerase chain reaction, revealed a significant increase in expression of Indian Hedgehog, glioma-associated oncogene homolog 1, Wnt, and cyclin D1. Laser capture microdissection analysis also showed a significant increase in Snail with a concomitant decrease in E-cadherin. CONCLUSIONS:  In the stomachs of adult mice, loss of Shh from parietal cells results in hypochlorhydria and hypergastrinemia. Hypergastrinemia might subsequently induce increased Hedgehog and Wnt signaling in the surface pit epithelium, resulting in hyperproliferation.



Ahn, JS, et al. (2013), ‘Acid suppressive drugs and gastric cancer: a meta-analysis of observational studies.’, World J Gastroenterol, 19 (16), 2560-68. PubMedID: 23674860
Beasley, DE, et al. (2015), ‘The Evolution of Stomach Acidity and Its Relevance to the Human Microbiome.’, PLoS One, 10 (7), e0134116. PubMedID: 26222383
Bray, G.W. (1931), ‘The Hypochorhydria of Asthma in Children’, Quart. J Med, XXIV 181-97. PubMedID:
Correia, JP and M de Moura (1963), ‘Tubeless gastric analysis with azure A and maximal histamine stimulation.’, Br Med J, 1 (5327), 365-68. PubMedID: 14023158
Dotevall, G. and A. Walan (1969), ‘Gastric secretion of acid and intrinsic factor in patients with hyper- and hypothyroidism’, Acta Med Scand, 186 (6), 529-33. PubMedID: 5382072
Hatta, W, et al. (2014), ‘Endoscopic findings for predicting gastric acid secretion status.’, Dig Endosc, PubMedID: 25556402
Iwai, W, et al. (2013), ‘Gastric hypochlorhydria is associated with an exacerbation of dyspeptic symptoms in female patients.’, J Gastroenterol, 48 (2), 214-21. PubMedID: 22829345
Malfertheiner, P (2011), ‘The intriguing relationship of Helicobacter pylori infection and acid secretion in peptic ulcer disease and gastric cancer.’, Dig Dis, 29 (5), 459-64. PubMedID: 22095010
Stockbrugger, RW, et al. (1982), ‘Intragastric nitrites, nitrosamines, and bacterial overgrowth during cimetidine treatment.’, Gut, 23 (12), 1048-54. PubMedID: 7173716
Van Dop, WA and GR Van Den Brink (2010), ‘Sonic hedgehog: a link between inflammation, gastric atrophy, and acid suppression’, Gastroenterology, 138 (2), 426-29. PubMedID: 20034600
Xiao, C, et al. (2010), ‘Loss of parietal cell expression of Sonic hedgehog induces hypergastrinemia and hyperproliferation of surface mucous cells.’, Gastroenterology, 138 (2), 550-61, 561.e1. PubMedID: 19909751