The atrophic changes markedly increase risk of gastric ulceration and non-cardia gastric adenocarcinoma ( 17, 18) but the lower acid production protects against duodenal ulceration, and probably against acid-induced complications of gastroesophageal reflux ( 19). pylori continues its proliferation and inflammation of gastric mucosa causing the progressive loss of gastric glands. If not detected or cured, the bacterium or H.

pylori ( 16), so this potentially creates a positive-feedback loop. Gastrin is a specific growth factor for H. pylori gastritis causes a reduction in somatostatin levels ( 13) and, since somatostatin negatively regulates gastrin, hypergastrinemia ensues ( 14, 15). pylori forges the stomach homeostasis inducing inflammation using proinflammatory cytokines and so influencing the activity of somatostatin-producing D cells, gastrin-producing G cells, and acid-producing parietal cells. VacA causes massive vacuolation in epithelial cell lines forming pores in their membranes, determining the output of anions and urea ( 12). The virulence of the bacteria strains is linked to the presence of a pathogenicity island (cagPAI) locus of its genoma that encodes for the bacterial oncoprotein CagA ( 11), T4SS and to another factor encoded by a different locus, the vacuolating cytotoxin A (VacA). It produces a huge amount of urease, that metabolizes the urea present in the stomach in ammonia and carbon dioxide in order to produce a neutralized area where the bacteria can live ( 10). Then it adheres to epithelial cells using the blood group antigen binding adhesin (BabA) that it binds to ABO/Leb (Leb) group antigens and fucosylated carbohydrates expressed by gastric epithelial cells ( 9). It has the ability to reach the protective mucus layer at the surface of gastric mucosa and to survive the extreme acid content of the stomach thanks to its 4-6 flagella, and by avoiding low pH areas using chemiotaxisit first colonizes the antrum, where there are no acid-producers cells. H.pylori is a gram-negative microaerophilic bacterium, that generally colonizes the stomach in early life ( 8). pylori has been established as a major cause of chronic gastritis and peptic ulcer, being in fact involved in the pathogenesis of gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Warren published on Lancet a paper in which they claimed the presence of “small curved and S shaped bacilli”, later classified as Helicobacter pylori ( 7). The mucosa of GERD patients produces significantly larger amounts of various cytokines ( 4) that activate immune cell recruitment and migration, and are involved in the pathophysiology of the illness. Other factors involved are a delay in gastric emptying, reduced oesophageal motility and an excessive stomach relaxation, but the variability of endoscopic findings depends on the different resistance and sensitivity of the individual patient’s esophagus. The pathophysiology of GERD is determined by a failure of the lower esophageal sphincter, that can be related to different factors such as hiatal hernia, obesity, pregnancy, drugs that act on the sphincter musculature, cigarette smoking.

However, more than 70% of patients that experience heartburn do not have visible lesions at endoscopy ( 5) and they are termed as NERD ( 6) (Non Erosive Reflux Disease). Probably a defective anti-reflux barrier and luminal clearance mechanisms are responsible for macroscopically detectable injury to the esophageal squamous epithelium ( 4), which concretizes in erosive esophagitis and Barrett’s Esophagus. According to Montreal classification, GERD is defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications ( 3). Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal conditions in the general population ( 1), but an universally accepted definition is lacking since 2006 ( 2). Reflux disease and esophagitis, definition and pathophysiology

Gord vs gerd