Impaired Gastric Secretion Research Articles

Using Capsule Enteroscopy Imaging to Analyze the Effects of Proton Pump Inhibitor Therapy and Its Association to Iron Deficiency Anemia

Purpose: For iron to be absorbed by the GI tract, it must be reduced from the ferric (Fe3+) to the ferrous (Fe2+) form. Impaired gastric secretion can lead to malabsorption and iron deficiency. Only a few studies in the past have investigated the link between proton pump inhibitor therapy (PPI) and iron deficiency anemia (IDA). In recent years, capsule enteroscopy (CE) has become a useful method to evaluate IDA and bleeding of obscure origin in patients with negative endoscopy and colonoscopy. CE, therefore, serves as a suitable imaging modality to analyze the link between PPI therapy use and IDA. Methods: We conducted a retrospective chart review on 200 patients who had a CE between January 1, 2007 and December 30, 2012 for various indications, including iron deficiency anemia, melena, and inflammatory bowel disease; 86 of the 200 patients were found to have a normal study. Of these 86 patients with a negative study, 52 patients had indications for iron deficiency anemia. Results: For the 52 patients with negative studies, we did a thorough chart review and found that half of them were taking a PPI prior to the study. Excluding three patients who were started on a PPI less than 2 weeks before the study, the average duration of PPI use was 570 days. Out of the 26 patients, 16 (61.5%) patients had their PPI ultimately terminated after our study. Interestingly, after iron supplementation, these patients were found to have a stable and improved hemoglobin level 12 months after the CE (Table 1). Conclusion: The majority of patients in our study had a CE after having a small bowel follow through, upper endoscopy, and colonoscopy. Previous studies have shown that combining camera-based scoping techniques and X-rays with radiopaque contrast serves as a model to detect a large number of pathologies within the gastrointestinal system. Therefore, based on our findings and prior negative studies, we believe there is an important association between PPI use and IDA. Healthcare providers should become aware of this link and be judicious with prescribing PPIs to their patients. Further case-controlled studies should be done to elucidate the connection as this may change future prescribing habits.Figure

Adverse effects of proton pump inhibitor drugs: clues and conclusions

To review evidence relating to the strength of associations that have appeared in largely observational studies, between high-dose or long-term use of proton pump inhibitor drugs and certain possibly attributable side-effects, which emerge from studies confounded by other variables. In retrospective studies not designed to assess safety, evidence of causality is generally lacking. The associations of fractures of hip, wrist, forearm and other sites appear weak and only slightly higher than the risks in control populations matched for age. They may increase with drug exposure, but probably do so only in individuals in whom other risk factors are also operational (smoking, alcohol, poor nutrition, steroids, etc.). The risks of Clostridium difficile colitis, other enteric infections, small bowel bacterial overgrowth and possibly spontaneous bacterial peritonitis also appear increased. Impaired gastric secretion may adversely affect the absorption of various nutrients, but their clinical impact is ill defined. Potentially more important are the consequences of hypergastrinemia, including rebound hypersecretion of acid, and possible development of various cancers, including carcinoid tumors. Effects of other drugs, including clopidogrel, on metabolism are reviewed, but clouded by uncertainties. The safety of long-term PPI administration needs serious prospective study.

Impaired gastric secretion and lack of trophic responses to hypergastrinemia in M 3 muscarinic receptor knockout mice

Background & Aims : The physiologic significance of the M 3 muscarinic receptor is unclear due to an absence of specific ligand. In the present study, M 3 receptor knockout (KO) mice were used to elucidate the role of M 3 receptors in gastric acid secretion and gastric mucosal integrity. Methods : M 3 KO versus wild-type mice aged 1 month to 2 years were included. Gastric acid secretion was assessed by both direct intragastric pH measurement and pylorus ligation. Serum gastrin and gastric mucosal histamine levels were determined by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Morphologic analysis was performed by both immunohistochemistry and transmission electron microscopy. Results : Fasted M 3 KO mice exhibited higher intragastric pH, lower acid output after pylorus ligation, a lower proportion of active parietal cells, and higher serum gastrin levels than fasted wild-type mice. Acid secretion in response to carbachol, histamine, gastrin 17, and 2-deoxy- d-glucose was impaired in the mutant mice. Although carbachol was still able to cause ∼30% acid output in M 3 KO mice, the acid secretion was inhibited by pirenzepine or famotidine. Despite remarkable hypergastrinemia in M 3 KO mice, there were no trophic responses in the oxyntic mucosa with respect to the mucosal thickness, proliferation rate, and numbers of parietal and enterochromaffin-like cells. Cholecystokinin type 2 receptor antagonist YM022 was without the effect in M 3 KO mice. Conclusions : The present study shows that M 3 receptors are essential for basal acid secretion, a fully acid secretory response to histamine and gastrin, and the trophic responses of oxyntic mucosa to gastrin.

Gastric Secretory and Serologic Studies on Patients With Neoplastic and Immunologic Disorders

Two-hour gastric acid and intrinsic factor (IF) secretory capacity determinations after betazole hydrochloride stimulation were performed on 21 patients with multiple myeloma, 10 each with lymphoproliferative disorders, rheumatoid arthritis, extragastric cancer, and 40 controls, all less than 65 years old. One patient with multiple myeloma had pernicious anemia (PA); four patients with multiple myeloma had close relatives with PA, gastric carcinoma, or thyroid disease. Two other elderly patients had myeloma and atrophic gastritis. Two patients with lymphoproliferative disorders had severely impaired gastric secretion. Parietal cell, IF, and thyroid autoantibodies were not detected in serum from any of the patients.