Peculiarities of the Pathology of Gastrointestinal Tract in Patients with Gastroesophageal Reflux Disease on the Background of Hypothyroidism

The article identifies the features of the pathology of the gastrointestinal tract in patients with gastroesophageal reflux disease on the background of hypothyroidism. The frequency of gastroesophageal reflux disease and the severity of this disease increase with age and the presence of comorbid pathology. In the elderly, the frequency of the typical esophageal manifestations decreases, and the erosive esophagitis with atypical symptoms is more common. The growing number of cases of combined thyroid dysfunction with gastropathology requires in-depth study of the reasons for the relationship between these processes. Pathological changes in the gastrointestinal tract in these patients make their condition severer, contributing to the development and progression of metabolic disorders. An important aggravating effect on the regulatory mechanisms of esophageal kinetics has a pathological functioning of the thyroid gland on the background of iodine deficiency. Results and discussion. In patients with gastroesophageal reflux disease with hypothyroidism, all changes in gastric and duodenal function are associated with a decrease in the acid-forming function of the gastric mucosa, due to its atrophy, decreased tone and contractility of the stomach. This in turn leads to a slowing of gastric and duodenal evacuation, dysfunction of the closing capacity of the cardia and, as a consequence, the development of duodenogastroesophageal reflux. The esophageal contents are not so pronounced, so patients with non-erosive forms of esophagitis predominate (46.2%) against 16% of patients in the second group (patients with gastroesophageal reflux disease). At the same time, erosive forms predominate among patients in the control group with predominant acid reflux. It should be noted that there is a clear relationship between the frequency of erosive changes in the esophageal mucosa and the duration of the disease. Thus, among patients of the main group with a 5-year history of the disease, the number of erosive forms of gastroesophageal reflux disease was minimal. The number of erosive changes in the esophageal mucosa increased sharply in patients with a 10-year history and reached its maximum after 15 years from the onset of the disease. Conclusion. The delay in gastric evacuation is more pronounced in patients with gastroesophageal reflux disease on the background of hypothyroidism. It can be explained by a decrease in gastric motility and the presence of duodenostasis. The slowing of gastric evacuation was more pronounced in patients with gastroesophageal reflux disease on the background of reduced thyroid function. In patients with gastroesophageal reflux disease on the background of hypothyroidism there is an alkaline duodenogastroesophageal reflux as a consequence of reduced acid-forming function of the gastric mucosa and reduced contractility of the stomach and duodenum

Duodenogastroesophageal reflux: current state of issue

The article presents data on modern views on the problem of duodenogastroesophageal reflux, examines the key features of the physiology of bile acids, the role of bile acids in the patho- genesis of gastroesophageal reflux disease, Barrett's esophagus and esophageal adenocarcinoma. The review presents current methods for diagnosing duodenogastroesophageal reflux, discusses treatment approaches.

Association of hepatobiliary pathology and gastroesophageal reflux disease

The problem of comorbidity with a high risk of polypragmasia is relevant in a large group of patients with diseases in the digestive system. Currently, the problem of comorbidity in patients with gastroesophageal reflux disease (GERD) attracts the attention of specialists due to the high disease prevalence and data indicating its association with other digestive system diseases, primarily of the hepatobiliary system. The article presents the results of clinical and experimental studies revealing the pathogenetic connections of GERD and hepatobiliary pathology accompanied by biliary dyskinesia, factors leading to an impairment of the duodenal propulsive activity. It is noted that the most important components of the esophageal mucosa lesion in duodenogastroesophageal reflux are bile acids, lysolecithin and pancreatic enzymes. The relevance of prescribing drugs that can affect the course of pathogenetically related diseases, which can significantly reduce the risk of polypragmasia, is justified. Such drugs include ursodeoxycholic acid, which, in the conditions of the GERD and hepatobiliary pathology association, contributes to the functional state normalization of the liver and biliary tract, reduces biliary dyskinesia, the severity of duodenal hypertension and duodenogastroesophageal reflux. The next example is the rebamipide cytoprotector, which has a multilateral protective effect against the mucous membrane of the GIT, including the esophagus, gastroduodenal zone, small intestine, as well as liver. The expediency of prescribing rebamipide to patients who are refractory to therapy with proton pump inhibitors is justified. KEYWORDS: comorbidity, hepatobiliary pathology, gastroesophageal reflux disease, ursodeoxycholic acid, rebamipid, proton pump inhibitors. FOR CITATION: Kazyulin A.N., Goncharenko A.Yu., Kalyagin I.E. Association of hepatobiliary pathology and gastroesophageal reflux disease. Russian Medical Inquiry. 2021;5(6):404–412 (in Russ.). DOI: 10.32364/2587-6821-2021-5-6-404-412.

Bile acids inhibit cholinergic constriction in proximal and peripheral airways from humans and rodents

Duodenogastroesophageal reflux (DGER) is associated with chronic lung disease. Bile acids (BAs) are established markers of DGER aspiration and are important risk factors for reduced post-transplant lung allograft survival by disrupting the organ-specific innate immunity, facilitating airway infection and allograft failure. However, it is unknown whether BAs also affect airway reactivity. We investigated the acute effects of 13 BAs detected in post-lung-transplant surveillance bronchial washings (BW) on airway contraction. We exposed precision-cut slices from human and mouse lungs to BAs and monitored dynamic changes in the cross-sectional luminal area of peripheral airways using video phase-contrast microscopy. We also used guinea pig tracheal rings in organ baths to study BA effects in proximal airway contraction induced by electrical field stimulation. We found that most secondary BAs at low micromolar concentrations strongly and reversibly relaxed smooth muscle and inhibited peripheral airway constriction induced by acetylcholine but not by noncholinergic bronchoconstrictors. Similarly, secondary BAs strongly inhibited cholinergic constrictions in tracheal rings. In contrast, TC-G 1005, a specific agonist of the BA receptor Takeda G protein-coupled receptor 5 (TGR5), did not cause airway relaxation, and Tgr5 deletion in knockout mice did not affect BA-induced relaxation, suggesting that this receptor is not involved. BAs inhibited acetylcholine-induced inositol phosphate synthesis in human airway smooth muscle cells overexpressing the muscarinic M3 receptor. Our results demonstrate that select BAs found in BW of patients with lung transplantation can affect airway reactivity by inhibiting the cholinergic contractile responses of the proximal and peripheral airways, possibly by acting as antagonists of M3 muscarinic receptors.

The role of the transcription factor Sox2 and cytokeratins in the formation and development of the gastroesophageal junction epithelial cell differon

The source of the origin of the epithelium of the cardiac part stomach mucosa has been repeatedly discussed in the literature and different variants of the transformation of the epithelium as manifestation of normal anatomical peculiarities of a man and as a result of changing the program of stem cell differentiation, migration of bone marrow cells, transdifferentiation of simple columnar epithelium have been proposed. Probably it is related to difficulties of studying insignificant in size epithelium of the cardiac mucosa itself and establishment of connection of the duodenogastroesophageal reflux with the development of metaplasia in the epithelium of the terminal department of the esophagus mucosa, which resembles its structure in the cardiac part of the stomach. The purpose of the research was to study the expression of the transcription factor Sox2 and the distribution of cytokeratins in the epithelium of the gastroesophageal zone during the stages of the embryonic and fetal periods of ontogenesis. According to the purpose of the research, an immunohistochemical analysis of the epithelial differon of the esophageal-gastric junction (GEJ) was used. The current study was carried out on 169 human embryos and fetuses of gestational age from 4-5 till 38 weeks. It was established that the transcription factor Sox2 is expressed in basal epitheliocytes of GEJ in all terms of observation and plays a major role in the development, differentiation and formation of the epithelial cell lineage of GEJ. The peculiarity of expression of cytokeratin 7 was positive marking in the cytoplasm of spinosum epitheliocytes, despite the negative expression in the basal layer. It showed weak expression in the epitheliocytes of the esophageal part of the GEJ in the embryonic period with an increased reaction in the embryo-fetal period and with subsequent disappearance, starting at 14 weeks in the early fetal period. For the cardiac mucous membrane GEJ was characterized by its moderate expression on all terms of observation. Cytokeratin 8/18 is embryo-fetal for the esophageal part of the esophagus, as it is defined in early periods of embryogenesis and disappears in the late period (28-38 weeks). For the cardiac mucous membrane GEJ was characterized by its moderate expression on all terms of observation. Cytokeratin 14, unlike CK7 and CK8/18, was localized in the cytoplasm and membranes of basal epitheliocytes of the esophageal part of the mucosa from the 17 gestational weeks and was absent in the gastrointestinal part of the GEJ throughout the prenatal period. Thus, our data on the expression of the transcription factor Sox2 and cytokeratins in the GEJ epithelial differon in the prenatal period of ontogenesis will improve the diagnostic accuracy in determining tissue or organ belonging and can be widely used in various GEJ diseases.

PS01.142: THE IMPACT OF CERVICAL LYMPH NODE DISSECTION ON ACID AND DUODENOGASTROESOPHAGEAL REFLUX AFTER INTRATHORACIC ESOPHAGOGASTROSTOMY FOLLOWING TRANSTHORACIC ESOPHAGECTOMY

Background The aim of this study was to evaluate the impact of cervical lymph node dissection on acid and duodenogastroesophageal reflux (DGER) in patients undergoing transthoracic esophagectomy with gastric tube reconstruction and intrathoracic esophagogastrostomy. Methods Thirty one patients receiving transthoracic esophagectomy gastric tube reconstruction by intrathoracic esophagogastrostomy were subjected and divided into two groups: two field lymph node dissection group (the 2F group) and three field lymph node dissection group (the 3F group). All patients underwent 24h pH and bilirubin monitoring and gastrointestinal endoscopy one year after surgery. The results of 24h pH and bilirubin monitoring, endoscopic findings, and reflux symptoms, were compared between two groups. Results No acid reflux was observed in the 2F group, whereas it was observed in 6 (40%) of the 3F group (P = 0.023). DGER was observed in 2 patients (13%) of the 2F groups, whereas it was observed in 8 (53%) of the 3F group (P = 0.007). The percentage time of acid reflux in the 3F group was significant higher than that in the 2F group (median 0.8 vs 0%, P = 0.008). The percentage time of bile reflux in the 3F group was also significantly higher than that in the 2F group (median 2.600 vs 0%, P = 0.027). Four patients (25%) had reflux esophagitis in the 2F group, and nine patients (60%) had reflux esophagitis in the 3F group (P = 0.048). Conclusion Cervical lymph node dissection increases acid reflux and duodenogastroesophageal reflux, and can lead to the increase of the incidence of reflux esophagitis in patient with intrathoracic esophagogastrostomy. Disclosure All authors have declared no conflicts of interest.