This work demonstrated the differences in acidity of gastric juices among patients with upper gastrointestinal diseases. EU and DU patients had a higher gastric acidity than HSs. In contrast, GU and GC patients had a lower gastric acidity than HSs. This study is the first to verify higher gastric acidity in EU patients compared with HSs. In this study, only 5% of EU patients possessed hypoacidity of gastric juice, whereas gastric hypoacidity existed in 22%, 29% and 88% of HSs, GU and GC patients, respectively. The data imply that normal or higher acidity of gastric juice is an important factor for the development of GERD besides lower esophageal pressure abnormalities, hiatal hernia and delayed gastric emptying[20
Several histological studies also showed chronic atrophic gastritis present in 80%-90% of GC patients[21
]. In this study, gastric hypoacidity existed in 88% of the patients with GC. This finding indicates atrophic gastritis with gastric hypoacidity is a crucial step for the development of gastric adenocarcinoma. H. pylori
infection, old age and cagA and vacA m1 positivity have been identified as independent risk factors for the development of atrophic gastritis[22
]. We propose that the high prevalence of H. pylori
infection, advanced age, some bacterial virulent factors and susceptible host factors may contribute to the development of gastric atrophy and hypoacidity of the GC patients in this study.
The current work also showed that DU patients had a higher gastric acidity than HSs. This result supported previous observations demonstrating increased basal and stimulated acid secretion by the body of the stomach and increased acid load in the duodenum in patients with DU[23
]. On the contrary, GU patients in this study had a lower gastric acidity than HSs, suggesting that mucosal defensive impairments are more important than increased acid load in the pathogenesis of GU. The findings were consistent with previous reports[24
] revealing that the majority of gastric ulcers do not have increased gastric acid secretion.
Multivariate analysis in this study revealed that bile stain of gastric juice, high acute inflammatory score and atrophy of the corpus were independent factors for the development of gastric hypoacidity. The atrophy of the corpus was the most important factor for gastric hypoacidity with an odds ratio of 3.5. Since gastric acid is secreted by the parietal cells in the corpus, gland atrophy of the corpus leading to hyposecretion of acid and gastric hypoacidity is logical.
In 1988, Correa et al[25
] proposed a human model of gastric carcinogenesis that gastric cancers develop through a complex sequence of events from normal mucosa to superficial gastritis, atrophic gastritis, intestinal metaplasia, dysplasia and finally to intestinal-type adenocarcinoma[21,26,27
]. Gland atrophy resulting in hypochlorhydria is a key step in this theory and accounts for gastric bacterial colonization, reduction of dietary nitrates to nitrites and the formation of potentially carcinogenic N-nitroso compounds[4,25
]. In this study, H. pylori
-infected patients had higher frequencies of gland atrophy in the corpus (38% vs
21%) and gastric hypoacidity (37% vs
26%) than uninfected subjects. Additionally, they also had stronger acute and chronic inflammation in the corpus than uninfected subjects. These findings suggest that H. pylori
infection is an important factor contributing to the development of atrophic gastritis in the corpus and hypo-secretory status of the stomach.
Primary duodenogastric reflux may occur due to antroduodenal motility disorder or incompetent pyloric sphincter[28
]. The retrograded bile and duodenal contents can induce damage of the gastric mucosa[29
]. It has been observed that duodenogastric reflux plays a crucial role in the pathogenesis of alkaline gastritis and GU[29
]. Since the presence of bile in the gastric juice implies retrograde passage of alkaline duodenal contents into the stomach, it is reasonable to expect increased pH levels of gastric juice in the subjects with bile in gastric juice.
A higher degree of acute inflammation was the other histological factor predicting gastric hypoacidity in this study. Currently, we have no definite rationale to explain the association between dense neutrophil infiltrate and increased pH level in gastric juices, but dense neutrophil infiltrates may reflect the high density of H. pylori
in the stomach[30
], and have also been reported as one of the important factors related to the progression of atrophic gastritis[26
In this study, smokers had a trend of less hypoacidity than non-smokers. The finding was supported by previous studies showing that nicotine increases acid secretion and decreases prostaglandin synthesis[31
]. It is interesting to note that alcohol drinkers also had a trend of less hypoacidity than nondrinkers. The reasons for this finding remain unclear, but some studies demonstrated that fermented and nondistilled alcoholic beverages increase gastrin levels and acid secretion[32
]. Additionally, succinic and maleic acid contained in certain alcoholic drinks also stimulate acid secretion[32
In conclusion, bile reflux, atrophy and neutrophil infiltration of the corpus are three independent factors determining the acidity of gastric juices. Gastric acidities in patients with various upper gastrointestinal diseases are quite different. EU and DU patients have a higher gastric acidity whereas GU and GC patients have a lower gastric acidity compared with HSs.