Gastroesophageal reflux disease (GERD) is characterized by impaired motility at the gastroesophageal junction and the development of inflammatory changes in the mucosa of the distal esophagus. The aim of this review is to discuss the mechanisms contributing to the development of GERD. A literature search was conducted using the eLibrary.Ru and PubMed databases, focusing on articles published after 2000. Following the application of selection criteria, a total of 80 articles were included in the final literature review. Current understanding suggests that reflux esophagitis begins with damage to the esophageal epithelium caused by the reflux of acid and pepsin, leading to increased epithelial permeability. This allows hydrochloric acid and pepsin to penetrate deeper into the epithelial layer, attacking intact cells. Research indicates that the mechanisms of epithelial damage in the esophagus induced by acidic and bile reflux differ. Acid reflux causes tissue damage through protein denaturation, degradation by proteases, activation of cyclooxygenase-2 (COX-2), c-myc, and mitogen-activated protein kinase pathways, while simultaneously limiting prostaglandin synthesis. In contrast, bile acids induce cytotoxic mechanisms, activating oncogenes and c-myc, which contribute to epigenetic carcinogenic processes. Alterations in the esophageal microbiome trigger the activation of both innate and adaptive immune systems, as well as the sensory nervous system. Immune competent cells express receptors for numerous mediators released by sensory and autonomic nerves, enabling the nervous system to directly regulate the functional activity of the immune system. Conversely, immune cells can produce neuroactive substances and modulate nervous system functions, including pacemaker cells, leading to the development of reflux and exposing the esophageal mucosa to hydrochloric acid and pepsin or bile acids, resulting in inflammation and creating a vicious cycle.
This article describes the role of Moritz Hoffmann, anatomist and professor of medicine and surgery, in the history of the discovery of the pancreatic duct, later named after Johann Georg Wirsung. Translations of original texts in Latin are provided, their authors were contemporaries, eyewitnesses, and scientists who were directly acquainted with the participants of those events.
Objective: To determine the changes in organs and systems associated with connective tissue dysplasia (CTD) that affect gastric acid production in patients with CTD presenting symptoms of dyspepsia. Materials and Methods: A randomized controlled cross-sectional comparative study was conducted involving a total of 151 participants using a cross-sectional design. Inclusion criteria included presence of dyspeptic symptoms, absence of severe organic pathology capable of manifesting as dyspeptic symptoms (fever, hematemesis, anemia, leukocytosis, elevated ESR, melena), peptic ulcers or erosions in the stomach and duodenum mucosa, age between 18 to 29 years old, no history of Helicobacter pylori eradication therapy, discontinuation of medications affecting gastric acidity according to their half-life period, informed consent for participation in the study. All enrolled subjects underwent general clinical examination (collection of complaints, medical history, physical examination), screening for CTD, assessment of vegetative vascular reactivity (“Nerosoft,” Russia). Since there are no clear reference values for gastric acid-producing function, two additional groups without dyspepsia were formed using the same inclusion criteria except for the presence of dyspeptic symptoms. The research cohort consisted of four groups: Group 1-42 patients with dyspepsia and CTD; Group 2-36 patients with dyspepsia but no CTD; Group 3-37 patients with CTD but no dyspeptic complaints; Group 4-37 healthy volunteers free from both CTD and dyspeptic symptoms. All four groups received comprehensive clinical evaluation including symptom questionnaires using the Gastrointestinal Symptom Rating Scale (GSRS), 24-hour pH-metry (“Gastronscan-24,” Fryazino, Moscow Region, Russia), measurement of serum levels of pepsinogens I and II, gastrin-17, anti-H. pylori IgG antibodies (“Vector-Best,” Novosibirsk, Russia), endoscopic laser Doppler flowmetry (“LAKK-2,” Russia). Results: Among patients with CTD experiencing dyspeptic symptoms, postprandial distress syndrome occurred in 77% of cases. Clinico-functional markers specific to biliary type dysfunction include reflux-gastritis (17.8%) and gallbladder deformation (30%). Markers indicative of hypoacid condition include impaired microcirculation in the gastric wall (26.2%), gastropathy (gastric ptosis, 42%), thoracic cage deformities (23%), hypergastrinemia (25.6%). Conclusion: Decreased gastric acid secretion in patients with CTD is caused by two primary mechanisms. The most common factor involves disturbed gastric motility leading to duodenogastric reflux, resulting in bile entering the stomach and disrupting its secretory activity. In some patients, this process progresses to atrophic changes in the gastric mucosa accompanied by true deficiency in hydrochloric acid production. Both mechanisms significantly reduce the stomach's ability to produce acid, thereby influencing digestive processes and gastrointestinal protective properties.
Treatment of gastroesophageal reflux disease (GERD) is an urgent problem of modern gastroenterology. According to numerous studies carried out from 2000 to 2011, the prevalence of GERD varies depending on the region of the world from 2.5% (in East Asia) to 33.1% (in the Middle East). Moreover, according to various authors, the rate of failure of GERD therapy can reach 40%. Today there is no general accepted definition of “refractoriness” in all professional communities. In the clinical guidelines for the diagnosis and treatment of GERD of the Russian Gastroenterological Association (RGA), refractoriness is understood as the persistence of typical symptoms of the disease and/or incomplete healing of the esophageal mucosa while taking a standard dose of proton pump inhibitors (PPIs) once a day for 8 weeks. It should be noted that it is legitimate to talk about the refractory form of GERD in the case when the diagnosis of GERD was verified according to current clinical recommendations, treatment was prescribed according to the identified phenotype of the disease, but the therapy administered to the patient is accompanied by a partial effect. The article presents the basic principles of treatment a patient with gastroesophageal reflux disease refractory to proton pump inhibitor therapy. An algorithm for identifying and eliminating possible causes of refractoriness is proposed, taking into account the phenotype of the disease and the presence of concomitant pathology.
The article provides information on the role of the FTO (A+23525T) fat mass-associated gene polymorphism, the leptin receptor gene LEPR (Arg223Gln) in BEN syndrome in patients with DST. The results of the study of the trophological status of patients with DST and the severity of BEN syndrome are shown. It has been proven that genetic mutations exacerbate genetically determined disorders of the trophological status. In practice, the doctor must take into account the mechanisms of the formation of BEN syndrome in patients with DST and the risks associated with the presence of this syndrome.
