Materiały źródłowe

• #1

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2639970/

  Gastro-oesophageal reflux disease is a condition in which the reflux of gastric contents into the oesophagus provokes symptoms or complications and impairs quality of life. […] The pathogenesis of gastro-oesophageal reflux disease is multifactorial, involving transient lower oesophageal sphincter relaxations and other lower oesophageal sphincter pressure abnormalities. […] Other factors contributing to the pathophysiology of gastro-oesophageal reflux disease include hiatal hernia, impaired oesophageal clearance, delayed gastric emptying and impaired mucosal defensive factors. […] Hiatal hernia contributes to gastro-oesophageal reflux disease by promoting lower oesophageal sphincter dysfunction. […] Delayed gastric emptying, resulting in gastric distension, can significantly increase the rate of transient lower oesophageal sphincter relaxations, contributing to postprandial gastro-oesophageal reflux disease.

• #2

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2639970/

  While the pathogenesis of oesophageal symptoms is now well known, the mechanisms underlying extra-oesophageal airway manifestations are still poorly understood. […] In conclusion, gastro-oesophageal reflux disease can be considered as the result of a complex interplay of factors, all promoting the contact of gastric acidic contents with the oesophageal mucosa, leading to different degrees of oesophageal damage. […] As in other acid-related diseases, such as duodenal and gastric ulcer disease, GERD is thought to develop when aggressive factors, potentially harmful to the oesophagus, overcome protective mechanisms such as the oesophago-gastric junction barrier, oesophageal acid clearance and mucosal resistance, which normally contribute to maintain a physiologically balanced state. […] Therefore, a crucial role, in the pathogenesis of GERD, is played by contact with the oesophageal mucosa of refluxate, which can be composed of acid, pepsin, bile and duodenal contents.

• #3 Pathophysiology of gastroesophageal reflux disease – UpToDate

  https://www.uptodate.com/contents/pathophysiology-of-gastroesophageal-reflux-disease

  Pathophysiology of gastroesophageal reflux disease […] The pathophysiology of GERD will be reviewed here. The development of GERD reflects an imbalance between injurious or symptom-eliciting factors (reflux events, acidity of refluxate, esophageal sensitivity) and defensive factors (esophageal acid clearance, mucosal integrity). The extent of mucosal injury is proportional to the frequency of reflux events, the duration of esophageal mucosal acidification, and the caustic potency of refluxed fluid. Esophagitis results from cytokine-triggered inflammation rather than a direct chemical effect of prolonged exposure to acid, pepsin, and bile on the esophageal epithelium, the „burn” hypothesis. This is substantiated by the observation that histopathologic events during the development of esophagitis (lymphocytic inflammation, dilated intercellular spaces) occur deep in the epithelium, not at the luminal surface, and that regenerative changes (basal cell hyperplasia, papillary elongation) are initiated prior to the development of surface necrosis that was formerly hypothesized as the stimulus for those changes. Cytokine-triggered inflammation may also cause alterations in mucosal permeability and esophageal sensitivity in the absence of esophagitis.

• #4

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2639970/

  The mechanisms involved in the pathogenesis of GERD are multiple and include: a) motor abnormalities, such as impaired lower oesophageal sphincter (LES) resting tone, transient LES relaxations (TLESR), impaired oesophageal acid clearance and delayed gastric emptying; b) anatomical factors, such as hiatal hernia; c) visceral hypersensitivity; d) impaired mucosal resistance. […] A hiatal hernia is frequently found in patients with GERD. […] Whether or not the hernia is an initiating factor in GERD, it clearly plays a role in sustaining GERD, accounting for the chronicity of the disease. […] This mechanism is responsible for impaired acid clearance associated with GERD. […] A subset of subjects with GERD symptoms has been shown to experience hypersensitivity to pain in the absence of excessive oesophageal acid exposure.

• #5 Pathophysiology of Gastroesophageal Reflux Disease : Bariatric Times

  https://bariatrictimes.com/pathophysiology-of-gastroesophageal-reflux-disease/

  Gastroesophageal reflux disease (GERD) symptoms occur due to reflux of gastric contents into the esophagus. […] The pathophysiology of GERD is multifactorial. […] The antireflux barrier remains a critical component of GERD pathophysiology. […] Symptoms of GERD are due to mucosal injury from the caustic gastric fluid. […] The acidic fluid was thought to directly kill the esophageal epithelial cells, but newer data suggest that the gastric fluid causes the injured cells to attract inflammatory cells and eventually damage the mucosa. This is termed the cytokine sizzle. […] Whether or not injury in the esophagus is from chemical injury or the cytokine sizzle, the lower esophageal sphincter (LES) is a critical component of GERD physiology. […] The LES, crural diaphragm, angle of His, and the phrenoesophageal ligament form the antireflux barrier.

• #6 Gastroesophageal Reflux Disease: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/176595-overview

  Gastroesophageal reflux disease occurs when the amount of gastric juice that refluxes into the esophagus exceeds the normal limit, causing symptoms with or without associated esophageal mucosal injury (ie, esophagitis; see the image below). […] Gastroesophageal reflux disease (GERD) occurs when the amount of gastric juice that refluxes into the esophagus exceeds the normal limit, causing symptoms with or without associated esophageal mucosal injury (ie, esophagitis). […] The abnormalities that contribute to GERD can stem from any component of the system. Poor esophageal motility decreases clearance of acidic material. A dysfunctional LES allows reflux of large amounts of gastric juice. Delayed gastric emptying can increase the volume and pressure in the reservoir until the valve mechanism is defeated, leading to GERD. From a medical or surgical standpoint, it is extremely important to identify which of these components is defective so that an effective therapy can be applied.

• #7 SciELO Brazil – GASTROESOPHAGEAL REFLUX DISEASE: A PRACTICAL APPROACH GASTROESOPHAGEAL REFLUX DISEASE: A PRACTICAL APPROACH

  https://www.scielo.br/j/ag/a/B6dFcGXNt6LKQT8WYkpZYnD/

  Gastroesophageal reflux disease (GERD) presents typical manifestations such as heartburn and/or regurgitation as well as atypical manifestations such as throat symptoms, laryngitis, hoarseness, chronic cough, asthma, and sleep alterations. […] The process by which gastroesophageal reflux causes GERD consists of a sequence of events that involve the esophagogastric junction (EGJ) and esophageal body, as well as mechanisms of visceral sensitivity regulation mediated by the central and peripheral nervous system. The imbalance between protective and aggressive factors is responsible for the development of GERD. […] The main protective factors are the lower esophageal sphincter (LES), saliva, peristalsis, and the angle of esophageal passage through the hiatus (angle of Hiss). The aggressive factors are represented by the transient lower esophageal sphincter relaxations, hypotension of the LES, refluxed gastric acid pH, increased distensibility of the LES, prolonged esophageal clearance, reduced gastric emptying speed, and hiatus hernia.

• #8 GERD (Acid Reflux, Heartburn) Symptoms, Treatment, Foods, Diet

  https://www.medicinenet.com/gastroesophageal_reflux_disease_gerd/article.htm

  GERD is a condition in which the liquid content of the stomach regurgitates into the esophagus, often causing heartburn. […] The liquid can inflame and damage the lining (esophagitis) although visible signs of inflammation occur in a minority of patients. The regurgitated liquid usually contains acid and pepsin produced by the stomach. Acid is believed to be the most injurious component of the refluxed liquid. […] The action of the lower esophageal sphincter (LES) is perhaps the most important factor (a mechanism) for preventing reflux. […] Several different abnormalities of the LES have been found in patients with GERD. […] The first is an abnormally weak contraction of the LES, which reduces its ability to prevent reflux. […] The second is abnormal relaxations of the LES, called transient LES relaxations.

• #9 Pathophysiology of gastroesophageal reflux disease—which factors are important? – Fuchs – Translational Gastroenterology and Hepatology

  https://tgh.amegroups.org/article/view/5788/html

  The weakness of the natural antireflux barrier at the cardia obviously plays an important role in the pathophysiology of GERD. […] As published in multiple studies, LES-incompetence either via decreased intraabdominal length, overall shortening of LES-length, and/or decreased LES-pressure, has been demonstrated in severe GERD. […] The malfunction of the anatomical and functional components of the antireflux barrier plays a major role in allowing for pathologic gastroesophageal reflux. […] Our findings support the contribution of DGER to the pathophysiology of GERD, particularly in Barrett patients. […] In conclusion, in our evaluation of GERD patients referred for surgical intervention, the most important pathophysiologic component in severe GERD, appears to be mechanical incompetence and anatomical alterations of the anti-reflux barrier.

• #10 Pathophysiology of gastroesophageal reflux disease : GI Motility online

  https://www.nature.com/gimo/contents/pt1/full/gimo21.html

  Gastroesophageal reflux disease (GERD) includes all consequences of reflux of acid or other irritants from the stomach into the esophagus. The main cause of gastroesophageal reflux is incompetence of the antireflux barriers at the esophagogastric junction. […] Gastric pepsin duodenal contents exacerbate the action of acid and deleterious effect on the production of esophagitis. […] The antireflux barriers include two „sphincter” mechanisms: the lower esophageal sphincter (LES), and the crural diaphragm that functions as an external sphincter. […] Gastroesophageal reflux occurs when LES pressure is lower than the intragastric pressure such as in LES hypotension, increased frequency of transient lower esophageal sphincter relaxation (TLESR), when the intragastric pressure increases. […] The severity of GERD increases progressively with reflux that is mainly in the postprandial period to that in the upright posture, to that in the supine or that is bipositional reflux. Nighttime reflux leads to severe GERD.

• #11 Specific Movement of Esophagus During Transient Lower Esophageal Sphincter Relaxation in Gastroesophageal Reflux Disease

  https://www.jnmjournal.org/journal/view.html?uid=12&vmd=Full

  Transient lower esophageal sphincter relaxation (TLESR) is the main mechanism of gastroesophageal reflux disease (GERD). […] TLESR occurs in patients with gastroesophageal reflux disease (GERD) and in controls. […] When TLESR was first identified, it was hypothesized that GERD patients would have a higher rate of TLESR. However, the majority of studies showed a similar rate of TLESR in healthy subjects and in GERD patients. […] TLESR events comprise the main mechanism leading to acid reflux and are responsible for 70% of acid-reflux episodes. […] Since GERD is characterized by reflux, TLESR plays an important role in the etiology of this condition. […] In contrast, several studies have reported that TLESR in patients with GERD is more correlated with acid reflux than that in the normal population.

• #12 Gastroesophageal Reflux Disease (GERD) | SJFM

  https://sanjosefuncmed.com/common-stomach-disorders/

  An important cause of GERD is related to failure of the valve mechanism which exists between the esophagus and the stomach, formed by the lower esophageal sphincter (LES) and the diaphragm, which normally prevents reflux of stomach contents into the esophagus. A decrease in pressure of the LES can allow esophageal reflux of gastric contents. Some patients with GERD have a constantly weak, low-pressure LES, which permits reflux every time the pressure in the stomach exceeds the LES pressure. Periodic relaxation of the LES in normal individuals is called transient lower esophageal sphincter relaxation (TLESR). When it becomes more frequent and prolonged, TLESRs are believed to contribute significantly to reflux disease. […] Recent studies have suggested that transient lower esophageal sphincter relaxation is the main mechanism underlying gastroesophageal reflux. In patients with GERD, TLESRs account for the majority of reflux episodes. Gastric distension (also known as intra-abdominal pressure or IAP) has been recognized as a major factor inducing TLESRs. We conclude that gastric distention, by significantly increasing the rate of transient LES relaxations in both normal subjects and patients with gastroesophageal reflux disease, may contribute to the postprandial increase in gastroesophageal reflux.

• #13 Pathophysiology of gastroesophageal reflux disease : GI Motility online

  https://www.nature.com/gimo/contents/pt1/full/gimo21.html

  The factors generally accepted as important for the development of gastroesophageal reflux disease (GERD) have been well documented. Abnormality of any one of these factors holds the potential to disturb the normal equilibrium. These factors include gastric acid and other refluxed contents; delayed gastric emptying; structural and physiologic antireflux mechanisms at the gastroesophageal region; transient lower esophageal sphincter relaxation (TLESR); esophageal clearance mechanisms; ingested irritants; ingested substances that alter gastric, lower esophageal sphincter (LES), or esophageal motor function; mucosal integrity and defense mechanisms; visceral hypersensitivity; and genetic factors. […] Despite the many factors that operate, four main fundamental factors stand out as most important: (1) gastric acid; (2) the structural integrity, function, and competence of the LES that either prevent or allow reflux; (3) the esophageal mucosal defense mechanisms that are primarily called into play when there is excess exposure of the mucosa to gastric acid; and (4) the sensory mechanisms that speak to symptoms. That is, an incompetent gastroesophageal reflux mechanism allows abnormal amounts of gastric acid to enter the esophagus, where the acid burden causes mucosal damage and/or symptoms.

• #14 Specific Movement of Esophagus During Transient Lower Esophageal Sphincter Relaxation in Gastroesophageal Reflux Disease

  https://www.jnmjournal.org/journal/view.html?uid=12&vmd=Full

  TLESR is triggered by gastric distension, which induces an autonomic reflex. […] Thus, we hypothesize that the esophageal motor responses and LMC during TLESR in patients with GERD may be different compared to those in the healthy population. […] However, the differences in UES pressure change, UES relaxation, and related motor responses during TLESR explain esophageal dynamics in subjects with and without GERD. […] Delayed esophageal emptying of refluxate may worsen the esophageal environment after gastroesophageal reflux. […] However, complete TLESR may be more important than incomplete TLESR in the pathogenesis of GERD. […] In conclusion, TLESR events did not differ between the GERD and control groups. UES responses after TLESR were reasonably regulated in patients with GERD. However, the paucity of TLESR-related esophageal contractions may be a concern in terms of enhanced mucosal damages in GERD patients.

• #15 Current Advancement on the Dynamic Mechanism of Gastroesophageal Reflux Disease

  https://www.ijbs.com/v17p4154.htm

  With an in-depth study of the pathogenesis of GERD, it is now generally believed that TLESR is the main cause of gastroesophageal reflux. TLESR refers to the transient spontaneous relaxation of the LES without swallowing. The relaxation time can last for 10-45 s or more, which is often accompanied by reflux of gastric and duodenal fluids. Although TLESR can occur in healthy people with normal LES pressure or in patients with GERD, the refluxed content is different. […] The EGJ pressure is mainly composed of the crural diaphragm tension and LES pressure. Among them, the crural diaphragm tension is affected by breathing movement, while LES tension is affected by swallowing movement. It has been found that the end-expiratory pressure of the EGJ comes from the LES, while the end-inspiratory pressure comes from the crural diaphragm tension under normal circumstances. Therefore, the abnormal anatomy and function of the crural diaphragm is another important factor that causes gastroesophageal reflux.

• #16 Pathophysiology of gastroesophageal reflux disease : GI Motility online

  https://www.nature.com/gimo/contents/pt1/full/gimo21.html

  Low LES pressure and abnormal reflux can also occur in certain diseases, most commonly with the collagen vascular disorders such as scleroderma, where damage to the muscle and to the excitatory cholinergic innervation occur. […] The acid load to the esophagus is greater in GERD patients, in part because more TLESRs are associated with reflux even though the number of TLESRs is more or less similar. […] The physiologic reason for the increased frequency of TLESR-associated reflux in GERD patients is unknown. […] The presence of a hiatus hernia impacts unfavorably on both of these sphincter mechanisms. […] The presence and location of the sling muscle has also been linked to maintenance of the acute angle of His at the greater curve aspect of the gastroesophageal junction, and the formation of a flap valve function that could also serve as an antireflux mechanism.

• #17

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2639970/

  The mechanisms involved in the pathogenesis of GERD are multiple and include: a) motor abnormalities, such as impaired lower oesophageal sphincter (LES) resting tone, transient LES relaxations (TLESR), impaired oesophageal acid clearance and delayed gastric emptying; b) anatomical factors, such as hiatal hernia; c) visceral hypersensitivity; d) impaired mucosal resistance. […] A hiatal hernia is frequently found in patients with GERD. […] Whether or not the hernia is an initiating factor in GERD, it clearly plays a role in sustaining GERD, accounting for the chronicity of the disease. […] This mechanism is responsible for impaired acid clearance associated with GERD. […] A subset of subjects with GERD symptoms has been shown to experience hypersensitivity to pain in the absence of excessive oesophageal acid exposure.

• #18 Pathophysiology of gastroesophageal reflux disease—which factors are important? – Fuchs – Translational Gastroenterology and Hepatology

  https://tgh.amegroups.org/article/view/5788/html

  The analysis of 728 patients with primary GERD in a tertiary surgical referral unit shows as pathophysiologic factors and contributors of the disease the presence of hiatal hernias (HH), the LES-incompetence, an IEM, delayed gastric emptying (DGE) and the presence of DGER. […] Most frequent factors are the presence of a hiatal hernia (95.4%) as major anatomic alteration and the LES-incompetence (too weak and/or too short LES) (88%). […] Another important factor is DGER, present in 55% of these GERD patients, in patients with histologic and endoscopic evidence of Barretts esophagus even 89%. […] In summary, presence a of hiatal hernia, a mechanically incompetent LES and the presence of duodenal juice contents in the esophageal lumen are the most frequent pathologic changes in GERD, followed by less frequent factors such as obesity, IEM, and DGE.

• #19 Gastroesophageal Reflux Disease: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/176595-overview

  A hiatal hernia may contribute to reflux via a variety of mechanisms. The lower esophageal sphincter may migrate proximally into the chest and lose its abdominal high-pressure zone (HPZ), or the length of the HPZ may decrease. The diaphragmatic hiatus may be widened by a large hernia, which impairs the ability of the crura to function as an external sphincter. Finally, gastric contents may be trapped in the hernial sac and reflux proximally into the esophagus during relaxation of the LES. […] Some studies have shown that GERD is highly prevalent in patients who are morbidly obese and that a high body mass index (BMI) is a risk factor for the development of this condition. The hypothesis that obesity increases esophageal acid exposure is supported by the documentation of a dose-response relationship between increased BMI and increased prevalence of GERD and its complications. Therefore, the pathophysiology of GERD in patients who are morbidly obese might differ from that of patients who are not obese. The therapeutic implication of such a premise is that the correction of reflux in patients who are morbidly obese might be better achieved with a procedure that first controls obesity.

• #20 Pathophysiology of gastroesophageal reflux disease : GI Motility online

  https://www.nature.com/gimo/contents/pt1/full/gimo21.html

  In the presence of a hiatus hernia, the diaphragmatic sphincter is distanced from the gastroesophageal junction and therefore loses its ability to function as an antireflux mechanism. […] The mechanisms whereby the hiatus hernia is related to a decreased LES pressure, decreased acid clearance, and increased reflux are multiple and not fully understood.

• #21 The Pathophysiologic Basis for Epidemiologic Trends in Gastroesophageal Reflux Disease | Abdominal Key

  https://abdominalkey.com/the-pathophysiologic-basis-for-epidemiologic-trends-in-gastroesophageal-reflux-disease/

  Apart from selectively restricting liquid as opposed to gas reflux, the opening diameter of the EGJ is a primary determinant of the volume of gastric juice entering the esophagus during a reflux event. […] The LES is a 3- to 4-cm segment of tonically contracted smooth muscle at the EGJ. […] The genesis of LES tone is a property of both the smooth muscle itself and of its extrinsic innervation. […] Prolonged manometric studies, done either bedside in a postprandial setting or using ambulatory manometry equipment, have facilitated the mechanistic analysis of how gastroesophageal reflux occurs. […] These investigations have come to focus on three dominant reflux mechanisms: (1) transient LES relaxations, without any necessary anatomic abnormality; (2) LES hypotension, again without necessarily invoking any anatomic abnormality; or (3) anatomic distortion of the EGJ inclusive of, but not limited to, hiatus hernia.

• #22 SciELO Brazil – GASTROESOPHAGEAL REFLUX DISEASE: A PRACTICAL APPROACH GASTROESOPHAGEAL REFLUX DISEASE: A PRACTICAL APPROACH

  https://www.scielo.br/j/ag/a/B6dFcGXNt6LKQT8WYkpZYnD/

  The EGJ involves the superposition of the lower esophageal sphincter and the diaphragmatic crura (DC) and represents the anti-reflux barrier, the main defensive factor. […] The main pathophysiological mechanism of GERD is the transient relaxation of the LES (TLESR). The TLESR is mediated by the vagus nerve and strongly influenced by the proximal gastric distension, food, or gas, which precipitate the activation of mechanoceptors adjacent to the cardia. […] Acid reflux is much more common than non-acid reflux in the etiopathogenesis of GERD: in less than 10% of the patients, the reflux may be weakly acid or even alkaline. […] Hiatal hernia (HH) is defined by the proximal migration of the LES in relation to the DC, which occurs mainly by the weakening or rupture of the phrenoesophageal ligament and results in a more incompetent anti-reflux barrier.

• #23 Gastroesophageal Reflux Disease (GERD) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK554462/

  Gastroesophageal reflux disease is a condition where the retrograde flow of the stomach contents into the esophagus or beyond into other regions such as oral cavity, larynx, or the lungs results in inflammation of the esophageal mucosa. […] Risk factors contributing to GERD include being older than 50, having a body mass index 30, smoking, anxiety, depression, and decreased physical activity. Medicines that modulate the lower esophageal sphincter pressure, including nitrates, calcium channel blocker agents, and anticholinergics, can also contribute to developing GERD. […] The reflux of gastric contents into the esophagus in healthy individuals is limited, and the refluxed contents are cleared through esophageal peristalsis. However, patients with GERD cannot clear these refluxed contents or produce protective physiological mechanisms. The underlying etiologies of GERD include but are not limited to: Transient relaxation of the lower esophageal sphincter or a low resting lower esophageal sphincter pressure, Hiatal hernia, Extrinsically increased intra-abdominal pressure, as in obesity, Intrinsically increased intra-abdominal pressure, as observed during pregnancy or in patients with high-volume ascites, Impaired esophageal motility, Impaired saliva production, Impaired esophageal mucosal defense mechanisms.

• #24 Current Advancement on the Dynamic Mechanism of Gastroesophageal Reflux Disease

  https://www.ijbs.com/v17p4154.htm

  The formation of hiatal hernia (HH) is the main cause of structural abnormalities at the EGJ, among which the increase in intra-abdominal pressure caused by various reasons is the most common cause. HH can also induce the occurrence of TLESR and its frequency is positively correlated with the size of the HH. […] Esophageal clearance capacity includes the neutralization of reflux by saliva, weight of food itself, and protrusion of esophageal peristalsis. The movement of the esophagus is divided into peristaltic and non-peristaltic contractions. Peristaltic contractions can effectively remove acidic contents of the stomach and duodenum that flow back into the esophagus. However, non-peristaltic contractions are ineffective because of their reduced ability to remove refluxed contents, resulting in prolonged contact with acid and further aggravation of esophageal mucosal damage. […] GERD is a complex disease caused by multiple factors, and its pathogenesis has not been fully elucidated. Among them, LES structural abnormalities, hiatal hernia, and esophageal peristalsis dysfunction may play an important role in the pathogenesis of GERD.

• #25 GERD (Acid Reflux, Heartburn) Symptoms, Treatment, Foods, Diet

  https://www.medicinenet.com/gastroesophageal_reflux_disease_gerd/article.htm

  The most recently described abnormality in patients with GERD is the laxity of the LES. […] Hiatal hernias contribute to reflux, although how they contribute is not clear. […] When the LES moves into the chest with a hiatal hernia, the diaphragm, and the LES continue to exert their pressures and barrier effect. However, they now do so at different locations. […] When the wave of contraction is defective, refluxed acid is not pushed back into the stomach. […] Such abnormalities of contraction, which reduce the clearance of acid from the esophagus, are found frequently in patients with GERD. […] Most reflux during the day occurs after meals. […] A minority of patients with GERD has been found to have stomachs that empty abnormally slowly after a meal. […] The slower emptying of the stomach prolongs the distention of the stomach with food after meals.

• #26 Current Advancement on the Dynamic Mechanism of Gastroesophageal Reflux Disease

  https://www.ijbs.com/v17p4154.htm

  The formation of hiatal hernia (HH) is the main cause of structural abnormalities at the EGJ, among which the increase in intra-abdominal pressure caused by various reasons is the most common cause. HH can also induce the occurrence of TLESR and its frequency is positively correlated with the size of the HH. […] Esophageal clearance capacity includes the neutralization of reflux by saliva, weight of food itself, and protrusion of esophageal peristalsis. The movement of the esophagus is divided into peristaltic and non-peristaltic contractions. Peristaltic contractions can effectively remove acidic contents of the stomach and duodenum that flow back into the esophagus. However, non-peristaltic contractions are ineffective because of their reduced ability to remove refluxed contents, resulting in prolonged contact with acid and further aggravation of esophageal mucosal damage. […] GERD is a complex disease caused by multiple factors, and its pathogenesis has not been fully elucidated. Among them, LES structural abnormalities, hiatal hernia, and esophageal peristalsis dysfunction may play an important role in the pathogenesis of GERD.

• #27

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2639970/

  The mechanisms involved in the pathogenesis of GERD are multiple and include: a) motor abnormalities, such as impaired lower oesophageal sphincter (LES) resting tone, transient LES relaxations (TLESR), impaired oesophageal acid clearance and delayed gastric emptying; b) anatomical factors, such as hiatal hernia; c) visceral hypersensitivity; d) impaired mucosal resistance. […] A hiatal hernia is frequently found in patients with GERD. […] Whether or not the hernia is an initiating factor in GERD, it clearly plays a role in sustaining GERD, accounting for the chronicity of the disease. […] This mechanism is responsible for impaired acid clearance associated with GERD. […] A subset of subjects with GERD symptoms has been shown to experience hypersensitivity to pain in the absence of excessive oesophageal acid exposure.

• #28 Pathophysiology of gastroesophageal reflux disease : GI Motility online

  https://www.nature.com/gimo/contents/pt1/full/gimo21.html

  Hiatal hernia results from multiple mechanisms and is associated with a decreased LES pressure, decreased acid clearance, increased reflux, and more severe esophagitis. […] Mucosal defense mechanisms may be overcome by prolonged exposure of the esophageal mucosa to a pH 4 that may lead to severe and complicated esophagitis. […] Esophageal mucosal inflammation may affect nerves and muscle that alter LES function and esophageal body motility. A vicious cycle of inflammation and impaired motility may cause progressive disease. […] Patients with GERD may develop endoscopically visible erosive esophagitis or endoscopically negative nonerosive or negative endoscopy reflux disease (NERD). In NERD, factors such as visceral hypersensitivity or more proximal reflux of acid or nonacid material may be important. Acid and inflammatory mediators may gain access to sensory pathways and produce symptoms either by a direct action on the nerves or by producing abnormal muscle contraction.

• #29

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2639970/

  Gastro-oesophageal reflux disease is a condition in which the reflux of gastric contents into the oesophagus provokes symptoms or complications and impairs quality of life. […] The pathogenesis of gastro-oesophageal reflux disease is multifactorial, involving transient lower oesophageal sphincter relaxations and other lower oesophageal sphincter pressure abnormalities. […] Other factors contributing to the pathophysiology of gastro-oesophageal reflux disease include hiatal hernia, impaired oesophageal clearance, delayed gastric emptying and impaired mucosal defensive factors. […] Hiatal hernia contributes to gastro-oesophageal reflux disease by promoting lower oesophageal sphincter dysfunction. […] Delayed gastric emptying, resulting in gastric distension, can significantly increase the rate of transient lower oesophageal sphincter relaxations, contributing to postprandial gastro-oesophageal reflux disease.

• #30 Gastroesophageal Reflux Disease: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/176595-overview

  The lower esophageal sphincter (LES) is defined by manometry as a zone of elevated intraluminal pressure at the esophagogastric junction. For proper LES function, this junction must be located in the abdomen so that the diaphragmatic crura can assist the action of the LES, thus functioning as an extrinsic sphincter. In addition, the LES must have a normal length and pressure and a normal number of episodes of transient relaxation (relaxation in the absence of swallowing). […] The postulated mechanism by which delayed gastric emptying may cause GERD is an increase in the gastric contents resulting in increased intragastric pressure and, ultimately, increased pressure against the lower esophageal sphincter. This pressure eventually defeats the LES and leads to reflux. However, objective studies have produced conflicting data regarding the role of delayed gastric emptying in the pathogenesis of GERD.

• #31 SciELO Brazil – GASTROESOPHAGEAL REFLUX DISEASE: A PRACTICAL APPROACH GASTROESOPHAGEAL REFLUX DISEASE: A PRACTICAL APPROACH

  https://www.scielo.br/j/ag/a/B6dFcGXNt6LKQT8WYkpZYnD/

  After meals, it was observed that the content that refluxes into the esophagus has comparatively more acid than the gastric body and stems from a region near the EGJ where an acid pouch is found, resulting from the neoformation of acidic supernatant from the parietal cells in the proximal gastric region. […] The rationale for slow gastric emptying rely on the hypothesis that this phenomenon generates gastric distension, which could trigger TLESR episodes. […] The presence of acid in the esophagus may also produce symptoms by inducing the spasm of the longitudinal muscles of the esophagus, which is one of the causes of heartburn. […] In patients with erosive esophagitis, a clear breakdown of the squamous epithelium barrier is observed, which allows the reflux components to stimulate nociceptors in the lamina propria, causing symptoms. In patients with non-erosive GERD, it has been suggested that a microscopic damage to the mucosa may be a factor associated with the development of symptoms. […] The perception of symptoms in GERD is related to the increased sensitivity of the esophagus to several stimuli. This visceral hypersensitivity could be a consequence of the positive regulation of peripheral afferent nerve receptors by the acid-induced inflammation.

• #32 Gastroesophageal Reflux Disease | Nutrition Guide for Clinicians

  https://nutritionguide.pcrm.org/nutritionguide/view/Nutrition_Guide_for_Clinicians/1342015/all/Gastroesophageal_Reflux_Disease

  Some degree of gastric reflux is physiologic, does not cause any symptoms or esophageal injury, and does not require treatment. Gastroesophageal reflux disease (GERD) is a syndrome of inappropriate backflow of gastric acid into the esophagus, which can result in inflammation and erosion of the esophageal mucosa. The pathophysiology involves defective lower esophageal sphincter function due to inappropriate sphincter relaxation. This condition may be exacerbated by alcohol intake, smoking, fatty foods, caffeine, chocolate, various medications (e.g., anticholinergics, calcium channel blockers), inadequate sphincter size or function, or abnormal sphincter position. […] Patients with Barretts esophagus are at high risk for developing esophageal adenocarcinoma. […] Diabetes mellitus can cause gastroparesis (which prolongs gastric emptying), resulting in increased gastric contents and gastric pressure. The increased pressure exerts abnormally high pressure on the lower esophageal sphincter and predisposes to reflux.

• #33 Gastroesophageal Reflux Disease: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/176595-overview

  The lower esophageal sphincter (LES) is defined by manometry as a zone of elevated intraluminal pressure at the esophagogastric junction. For proper LES function, this junction must be located in the abdomen so that the diaphragmatic crura can assist the action of the LES, thus functioning as an extrinsic sphincter. In addition, the LES must have a normal length and pressure and a normal number of episodes of transient relaxation (relaxation in the absence of swallowing). […] The postulated mechanism by which delayed gastric emptying may cause GERD is an increase in the gastric contents resulting in increased intragastric pressure and, ultimately, increased pressure against the lower esophageal sphincter. This pressure eventually defeats the LES and leads to reflux. However, objective studies have produced conflicting data regarding the role of delayed gastric emptying in the pathogenesis of GERD.

• #34 GERD (Acid Reflux, Heartburn) Symptoms, Treatment, Foods, Diet

  https://www.medicinenet.com/gastroesophageal_reflux_disease_gerd/article.htm

  The most recently described abnormality in patients with GERD is the laxity of the LES. […] Hiatal hernias contribute to reflux, although how they contribute is not clear. […] When the LES moves into the chest with a hiatal hernia, the diaphragm, and the LES continue to exert their pressures and barrier effect. However, they now do so at different locations. […] When the wave of contraction is defective, refluxed acid is not pushed back into the stomach. […] Such abnormalities of contraction, which reduce the clearance of acid from the esophagus, are found frequently in patients with GERD. […] Most reflux during the day occurs after meals. […] A minority of patients with GERD has been found to have stomachs that empty abnormally slowly after a meal. […] The slower emptying of the stomach prolongs the distention of the stomach with food after meals.

• #35 Gastroesophageal Reflux Disease (GERD) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK554462/

  The pathogenesis of GERD and the development of complications such as Barrett esophagus are mediated by cytokines rather than the results of chemical injury. Reflux esophagitis activates hypoxia-inducible factor (HIF)-2 alpha and nuclear factor kappa-light-chain-enhancer of activated B cells, causing increased levels of pro-inflammatory cytokines and the migration of inflammatory cells, particularly T cells, and damage to the esophagus.

• #36 Gastroesophageal Reflux Disease (GERD) | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/28304

  The pathogenesis of GERD and the development of complications such as Barrett esophagus are mediated by cytokines rather than the results of chemical injury. Reflux esophagitis activates hypoxia-inducible factor (HIF)-2 alpha and nuclear factor kappa-light-chain-enhancer of activated B cells, causing increased levels of pro-inflammatory cytokines and the migration of inflammatory cells, particularly T cells, and damage to the esophagus.

• #37 Pathophysiology of gastroesophageal reflux disease – UpToDate

  https://www.uptodate.com/contents/pathophysiology-of-gastroesophageal-reflux-disease

  Pathophysiology of gastroesophageal reflux disease […] The pathophysiology of GERD will be reviewed here. The development of GERD reflects an imbalance between injurious or symptom-eliciting factors (reflux events, acidity of refluxate, esophageal sensitivity) and defensive factors (esophageal acid clearance, mucosal integrity). The extent of mucosal injury is proportional to the frequency of reflux events, the duration of esophageal mucosal acidification, and the caustic potency of refluxed fluid. Esophagitis results from cytokine-triggered inflammation rather than a direct chemical effect of prolonged exposure to acid, pepsin, and bile on the esophageal epithelium, the „burn” hypothesis. This is substantiated by the observation that histopathologic events during the development of esophagitis (lymphocytic inflammation, dilated intercellular spaces) occur deep in the epithelium, not at the luminal surface, and that regenerative changes (basal cell hyperplasia, papillary elongation) are initiated prior to the development of surface necrosis that was formerly hypothesized as the stimulus for those changes. Cytokine-triggered inflammation may also cause alterations in mucosal permeability and esophageal sensitivity in the absence of esophagitis.

• #38

  https://www.xiahepublishing.com/2994-8754/JTG-2023-00011

  An alternative pathophysiology to the direct acid contact and disruption of the esophageal mucosal barrier involves cytokine expression and subsequent submucosal directed inflammatory damage back to the mucosa. […] The association between reflux-induced expression of HIF-2 and its effects on increasing pro-inflammatory cytokines further strengthens the argument that GERD-related esophageal luminal barrier disruptions are the result of more than just direct acid caustic damage. […] Clearly, there is increasing evidence that GERD involves, in at least some patients, cytokine-mediated pathophysiology. The main cytokines involved in the esophageal pathophysiological cascade of the esophagus are pro-inflammatory cytokines interleukin IL-8 and IL-1, which recruit inflammatory cells such as leukocytes and neutrophils.

• #39 NF-κB: A novel therapeutic pathway for gastroesophageal reflux disease?

  https://www.wjgnet.com/2307-8960/full/v10/i24/8436.htm

  Nuclear factor-kappa beta (NF-B) is an important transcription factor associated with inflammation, which regulates apoptosis, viral replication, tumor formation and autoimmunity in addition to the inflammatory response. Reflux can directly stimulate the esophageal epithelium to recruit a large number of inflammatory cells, activate NF-B and release inflammatory chemokines (such as interleukin (IL)-1, IL-6 and IL-8). The up-regulated inflammatory factors and inflammatory cells in turn further activate NF-B expression in esophageal epithelium. […] Our previous study suggested that the activation of NF-B in esophageal mucosa may be responsible for the interruption of epithelial barrier function caused by reflux. NF-B can be activated by different stimuli and is considered to be part of the systemic stress response. Based on the literature and our previous study results, it can be hypothesized that inhibition of NF-B activation may block the damage to the esophageal mucosal barrier caused by GERD.

• #40 Natural Products in the Management of Gastroesophageal Reflux Disease: Mechanisms, Efficacy, and Future Directions

  https://www.mdpi.com/2072-6643/17/6/1069

  The main component of stomach acid, hydrochloric acid (HCl), also plays a vital role in damaging the esophageal lining in GERD. […] HCl-induced damage causes an inflammatory response that aggravates tissue injury and contributes to the chronic nature of GERD. […] Furthermore, bile acids and pepsin exacerbate esophageal damage while chronic inflammation prolongs it. […] Recent research has indicated that imbalances in gut microbiota (dysbiosis) are another contributor to GERD. […] A detailed assessment of factors involved in the pathogenesis of GERD, including those aimed at restoring microbial balance, could help to identify possible therapeutic approaches that can reduce inflammation and protect the esophagus. […] The inflammatory response in GERD is driven by a cascade of biochemical events that include immune cell recruitment, cytokine release, and oxidative damage.

• #41 NF-κB: A novel therapeutic pathway for gastroesophageal reflux disease?

  https://www.wjgnet.com/2307-8960/full/v10/i24/8436.htm

  The pathogenesis of GERD involves the interaction of chemical, mechanical, psychological and neural mechanisms. […] The reflux insult to esophageal mucosa is the most important pathophysiological mechanism of GERD. However, the components of refluxate are diverse, and include gastric acid, bile acid, and pepsin. Each component has its unique destructive mechanism on the esophageal defense system and consequential impact. […] GERD activates inflammation when the epithelial barrier is disrupted, and NF-B is an important transcription factor associated with inflammation. Reflux can directly stimulate the esophageal epithelium to produce inflammatory cytokines, up-regulate NF-B expression, and release inflammatory chemokines such as IL-1, IL-6 and IL-8. Changes in the microenvironment in turn activate NF-B to form a positive feedback.

• #42

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2639970/

  While the pathogenesis of oesophageal symptoms is now well known, the mechanisms underlying extra-oesophageal airway manifestations are still poorly understood. […] In conclusion, gastro-oesophageal reflux disease can be considered as the result of a complex interplay of factors, all promoting the contact of gastric acidic contents with the oesophageal mucosa, leading to different degrees of oesophageal damage. […] As in other acid-related diseases, such as duodenal and gastric ulcer disease, GERD is thought to develop when aggressive factors, potentially harmful to the oesophagus, overcome protective mechanisms such as the oesophago-gastric junction barrier, oesophageal acid clearance and mucosal resistance, which normally contribute to maintain a physiologically balanced state. […] Therefore, a crucial role, in the pathogenesis of GERD, is played by contact with the oesophageal mucosa of refluxate, which can be composed of acid, pepsin, bile and duodenal contents.

• #43 Pathophysiology of gastroesophageal reflux disease : GI Motility online

  https://www.nature.com/gimo/contents/pt1/full/gimo21.html

  Gastroesophageal reflux disease (GERD) includes all consequences of reflux of acid or other irritants from the stomach into the esophagus. The main cause of gastroesophageal reflux is incompetence of the antireflux barriers at the esophagogastric junction. […] Gastric pepsin duodenal contents exacerbate the action of acid and deleterious effect on the production of esophagitis. […] The antireflux barriers include two „sphincter” mechanisms: the lower esophageal sphincter (LES), and the crural diaphragm that functions as an external sphincter. […] Gastroesophageal reflux occurs when LES pressure is lower than the intragastric pressure such as in LES hypotension, increased frequency of transient lower esophageal sphincter relaxation (TLESR), when the intragastric pressure increases. […] The severity of GERD increases progressively with reflux that is mainly in the postprandial period to that in the upright posture, to that in the supine or that is bipositional reflux. Nighttime reflux leads to severe GERD.

• #44 GERD (Acid Reflux, Heartburn) Symptoms, Treatment, Foods, Diet

  https://www.medicinenet.com/gastroesophageal_reflux_disease_gerd/article.htm

  GERD is a condition in which the liquid content of the stomach regurgitates into the esophagus, often causing heartburn. […] The liquid can inflame and damage the lining (esophagitis) although visible signs of inflammation occur in a minority of patients. The regurgitated liquid usually contains acid and pepsin produced by the stomach. Acid is believed to be the most injurious component of the refluxed liquid. […] The action of the lower esophageal sphincter (LES) is perhaps the most important factor (a mechanism) for preventing reflux. […] Several different abnormalities of the LES have been found in patients with GERD. […] The first is an abnormally weak contraction of the LES, which reduces its ability to prevent reflux. […] The second is abnormal relaxations of the LES, called transient LES relaxations.

• #45 Gastroesophageal reflux disease and heartburn Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/report/gastroesophageal-reflux-disease-and-heartburn

  Although acid is a primary factor in damage caused by GERD, other products of the digestive tract, including pepsin and bile, can also be harmful. […] If the pressure barrier is not enough to prevent regurgitation and acid backs up (reflux), peristaltic action of the esophagus serves as an additional defense mechanism, pushing the backed-up contents back down into the stomach. […] The band of muscle tissue called the LES is responsible for closing and opening the lower end of the esophagus, and is essential for maintaining a pressure barrier against contents from the stomach. For it to function properly, there needs to be interaction between smooth muscles and various hormones. If it weakens and loses tone, the LES cannot close completely after food empties into the stomach, and acid from the stomach backs up into the esophagus.

• #46 Pathophysiology of gastroesophageal reflux disease : GI Motility online

  https://www.nature.com/gimo/contents/pt1/full/gimo21.html

  Hiatal hernia results from multiple mechanisms and is associated with a decreased LES pressure, decreased acid clearance, increased reflux, and more severe esophagitis. […] Mucosal defense mechanisms may be overcome by prolonged exposure of the esophageal mucosa to a pH 4 that may lead to severe and complicated esophagitis. […] Esophageal mucosal inflammation may affect nerves and muscle that alter LES function and esophageal body motility. A vicious cycle of inflammation and impaired motility may cause progressive disease. […] Patients with GERD may develop endoscopically visible erosive esophagitis or endoscopically negative nonerosive or negative endoscopy reflux disease (NERD). In NERD, factors such as visceral hypersensitivity or more proximal reflux of acid or nonacid material may be important. Acid and inflammatory mediators may gain access to sensory pathways and produce symptoms either by a direct action on the nerves or by producing abnormal muscle contraction.

• #47 SciELO Brazil – GASTROESOPHAGEAL REFLUX DISEASE: A PRACTICAL APPROACH GASTROESOPHAGEAL REFLUX DISEASE: A PRACTICAL APPROACH

  https://www.scielo.br/j/ag/a/B6dFcGXNt6LKQT8WYkpZYnD/

  After meals, it was observed that the content that refluxes into the esophagus has comparatively more acid than the gastric body and stems from a region near the EGJ where an acid pouch is found, resulting from the neoformation of acidic supernatant from the parietal cells in the proximal gastric region. […] The rationale for slow gastric emptying rely on the hypothesis that this phenomenon generates gastric distension, which could trigger TLESR episodes. […] The presence of acid in the esophagus may also produce symptoms by inducing the spasm of the longitudinal muscles of the esophagus, which is one of the causes of heartburn. […] In patients with erosive esophagitis, a clear breakdown of the squamous epithelium barrier is observed, which allows the reflux components to stimulate nociceptors in the lamina propria, causing symptoms. In patients with non-erosive GERD, it has been suggested that a microscopic damage to the mucosa may be a factor associated with the development of symptoms. […] The perception of symptoms in GERD is related to the increased sensitivity of the esophagus to several stimuli. This visceral hypersensitivity could be a consequence of the positive regulation of peripheral afferent nerve receptors by the acid-induced inflammation.

• #48

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2639970/

  The mechanisms involved in the pathogenesis of GERD are multiple and include: a) motor abnormalities, such as impaired lower oesophageal sphincter (LES) resting tone, transient LES relaxations (TLESR), impaired oesophageal acid clearance and delayed gastric emptying; b) anatomical factors, such as hiatal hernia; c) visceral hypersensitivity; d) impaired mucosal resistance. […] A hiatal hernia is frequently found in patients with GERD. […] Whether or not the hernia is an initiating factor in GERD, it clearly plays a role in sustaining GERD, accounting for the chronicity of the disease. […] This mechanism is responsible for impaired acid clearance associated with GERD. […] A subset of subjects with GERD symptoms has been shown to experience hypersensitivity to pain in the absence of excessive oesophageal acid exposure.

• #49 Pathophysiology of gastroesophageal reflux disease : GI Motility online

  https://www.nature.com/gimo/contents/pt1/full/gimo21.html

  Hiatal hernia results from multiple mechanisms and is associated with a decreased LES pressure, decreased acid clearance, increased reflux, and more severe esophagitis. […] Mucosal defense mechanisms may be overcome by prolonged exposure of the esophageal mucosa to a pH 4 that may lead to severe and complicated esophagitis. […] Esophageal mucosal inflammation may affect nerves and muscle that alter LES function and esophageal body motility. A vicious cycle of inflammation and impaired motility may cause progressive disease. […] Patients with GERD may develop endoscopically visible erosive esophagitis or endoscopically negative nonerosive or negative endoscopy reflux disease (NERD). In NERD, factors such as visceral hypersensitivity or more proximal reflux of acid or nonacid material may be important. Acid and inflammatory mediators may gain access to sensory pathways and produce symptoms either by a direct action on the nerves or by producing abnormal muscle contraction.

• #50 SciELO Brazil – GASTROESOPHAGEAL REFLUX DISEASE: A PRACTICAL APPROACH GASTROESOPHAGEAL REFLUX DISEASE: A PRACTICAL APPROACH

  https://www.scielo.br/j/ag/a/B6dFcGXNt6LKQT8WYkpZYnD/

  After meals, it was observed that the content that refluxes into the esophagus has comparatively more acid than the gastric body and stems from a region near the EGJ where an acid pouch is found, resulting from the neoformation of acidic supernatant from the parietal cells in the proximal gastric region. […] The rationale for slow gastric emptying rely on the hypothesis that this phenomenon generates gastric distension, which could trigger TLESR episodes. […] The presence of acid in the esophagus may also produce symptoms by inducing the spasm of the longitudinal muscles of the esophagus, which is one of the causes of heartburn. […] In patients with erosive esophagitis, a clear breakdown of the squamous epithelium barrier is observed, which allows the reflux components to stimulate nociceptors in the lamina propria, causing symptoms. In patients with non-erosive GERD, it has been suggested that a microscopic damage to the mucosa may be a factor associated with the development of symptoms. […] The perception of symptoms in GERD is related to the increased sensitivity of the esophagus to several stimuli. This visceral hypersensitivity could be a consequence of the positive regulation of peripheral afferent nerve receptors by the acid-induced inflammation.

• #51 Functional Food in Relation to Gastroesophageal Reflux Disease (GERD)

  https://www.mdpi.com/2072-6643/15/16/3583

  Gastroesophageal reflux disease (GERD) is a prevalent condition characterized by troublesome symptoms and esophageal inflammation caused by the reflux of stomach contents. Common symptoms include burning chest pain, regurgitation, and difficulty swallowing, while extraesophageal manifestations such as coughing and hoarseness can also occur. Unhealthy dietary patterns high in fat, sugar, salt, and cholesterol contribute to the increasing incidence of chronic diseases like GERD within the aging global population. The pathogenesis of GERD involves various mechanisms, such as motor dysfunctions, hiatal hernias, and impaired mucosal resistance. The following factors may contribute to the development of GERD. Lower esophageal sphincter dysfunction prevents stomach contents from refluxing into the esophagus. It contracts between meals and relaxes during swallowing or transient LES relaxations (TLESRs). People with GERD experience symptoms when the LES relaxes more frequently. Enhanced proximal postprandial gastric acid pocket (PPAGP) is where, after a meal, highly acidic stomach contents can accumulate if they do not mix well with the consumed food. In individuals with GERD, the PPGAP is larger, more acidic, and persists longer than in those without GERD. Delayed gastric emptying prolongs the retention of acidic food in the stomach, thereby increasing reflux risk. Impaired esophageal peristalsis reduces clearance of refluxed acid, leading to increased damage and more severe GERD symptoms. Impaired esophageal mucosal defense against the gastric refluxate can breach the defensive barrier, resulting in mucosal damage. A hiatal hernia plays a crucial role in the development of GERD by interfering with the function of the LES. Individuals with GERD may have heightened sensitivity in their esophageal tissues to even small amounts of acid, resulting in symptoms such as heartburn, chest pain, and regurgitation.

• #52 Pathophysiology of gastroesophageal reflux disease : GI Motility online

  https://www.nature.com/gimo/contents/pt1/full/gimo21.html

  When mucosal damage occurs (esophagitis), a vicious cycle can ensue to accentuate and maintain the GERD. […] The GERD category also encompasses a group of patients that have nonerosive or negative endoscopy reflux disease (NERD). In these patients, esophageal acid exposure may be normal and factors such as visceral hypersensitivity or more proximal reflux of acid or nonacid material may be important. […] The antireflux mechanism has at least two „sphincter” mechanisms: the intrinsic muscular sphincter known as the lower esophageal sphincter (LES), and the diaphragm that functions as an external sphincter-like mechanism. […] Gastroesophageal reflux occurs when LES pressure is lower than intragastric pressure. […] The increased acid load in GERD patients and its relationship to low LES pressure and the severity of the esophagitis is also reflected in the pattern of reflux. The severity of GERD increases progressively from postprandial to upright, to supine, to bipositional reflux.

• #53 Gastroesophageal Reflux Disease (GERD) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK554462/

  Gastroesophageal reflux disease is a condition where the retrograde flow of the stomach contents into the esophagus or beyond into other regions such as oral cavity, larynx, or the lungs results in inflammation of the esophageal mucosa. […] Risk factors contributing to GERD include being older than 50, having a body mass index 30, smoking, anxiety, depression, and decreased physical activity. Medicines that modulate the lower esophageal sphincter pressure, including nitrates, calcium channel blocker agents, and anticholinergics, can also contribute to developing GERD. […] The reflux of gastric contents into the esophagus in healthy individuals is limited, and the refluxed contents are cleared through esophageal peristalsis. However, patients with GERD cannot clear these refluxed contents or produce protective physiological mechanisms. The underlying etiologies of GERD include but are not limited to: Transient relaxation of the lower esophageal sphincter or a low resting lower esophageal sphincter pressure, Hiatal hernia, Extrinsically increased intra-abdominal pressure, as in obesity, Intrinsically increased intra-abdominal pressure, as observed during pregnancy or in patients with high-volume ascites, Impaired esophageal motility, Impaired saliva production, Impaired esophageal mucosal defense mechanisms.

• #54 Gastroesophageal Reflux Disease (GERD) – Gastrointestinal Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gastrointestinal-disorders/esophageal-and-swallowing-disorders/gastroesophageal-reflux-disease-gerd

  Incompetence of the lower esophageal sphincter allows reflux of gastric contents into the esophagus, causing burning pain. […] The presence of reflux implies lower esophageal sphincter (LES) incompetence, which may result from a generalized loss of intrinsic sphincter tone or from recurrent inappropriate transient relaxations (ie, unrelated to swallowing). […] Factors that contribute to the competence of the gastroesophageal junction include the angle of the cardioesophageal junction, the action of the diaphragm, gravity (ie, an upright position), and the patient’s age. […] Factors that may contribute to reflux include weight gain, fatty foods, caffeinated or carbonated beverages, alcohol, tobacco smoking, and medications. […] GERD may lead to esophagitis, esophageal ulcer, esophageal stricture, Barrett esophagus (replacement of normal squamous epithelium of the distal esophagus with metaplastic columnar epithelium during the healing phase of acute esophagitis), and esophageal adenocarcinoma.

• #55 Acid Reflux / GERD – Esophageal Health | UCLA Health

  https://www.uclahealth.org/medical-services/gastro/esophageal-health/diseases-we-treat/acid-reflux-gerd

  Physical factors that increase the risk for GERD include obesity, pregnancy, and the presence of a hiatal hernia. Behaviors associated with an increased risk of GERD include tobacco and alcohol use, use of medications that can reduce LES pressure, consumption of large meals (especially before bedtime) and eating certain foods (caffeine, chocolate, peppermint or fatty foods).

• #56 Gastroesophageal Reflux Disease: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/176595-overview

  A hiatal hernia may contribute to reflux via a variety of mechanisms. The lower esophageal sphincter may migrate proximally into the chest and lose its abdominal high-pressure zone (HPZ), or the length of the HPZ may decrease. The diaphragmatic hiatus may be widened by a large hernia, which impairs the ability of the crura to function as an external sphincter. Finally, gastric contents may be trapped in the hernial sac and reflux proximally into the esophagus during relaxation of the LES. […] Some studies have shown that GERD is highly prevalent in patients who are morbidly obese and that a high body mass index (BMI) is a risk factor for the development of this condition. The hypothesis that obesity increases esophageal acid exposure is supported by the documentation of a dose-response relationship between increased BMI and increased prevalence of GERD and its complications. Therefore, the pathophysiology of GERD in patients who are morbidly obese might differ from that of patients who are not obese. The therapeutic implication of such a premise is that the correction of reflux in patients who are morbidly obese might be better achieved with a procedure that first controls obesity.

• #57

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2639970/

  The ability of the oesophageal mucosa to withstand injury is a determining factor in the development of GERD. […] When aggressive factors overwhelm the oesophageal defence, mucosal injury occurs. […] The exact aetiology of extra-oesophageal manifestations of GERD remains unknown. […] However, two main hypotheses, not necessarily mutually exclusive, have been proposed: direct contact of aspirated gastric refluxate with the upper airway and a vago-vagal reflex.

• #58 Gastroesophageal Reflux Disease (GERD) – Gastrointestinal Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gastrointestinal-disorders/esophageal-and-swallowing-disorders/gastroesophageal-reflux-disease-gerd

  Factors that contribute to the development of esophagitis include the caustic nature of the refluxate, the inability to clear the refluxate from the esophagus, the volume of gastric contents, and local mucosal protective functions. […] Lower esophageal sphincter incompetence and transient relaxations allow gastric contents to reflux into the esophagus and rarely into the larynx or lungs. […] Complications include esophagitis, esophageal stricture, Barrett esophagus, and esophageal adenocarcinoma. […] Diagnose clinically; do endoscopy in patients not responding to empiric treatment and consider advanced pH monitoring if endoscopy is normal in patients with typical symptoms.

• #59 Pathophysiology of gastroesophageal reflux disease : GI Motility online

  https://www.nature.com/gimo/contents/pt1/full/gimo21.html

  Hiatal hernia results from multiple mechanisms and is associated with a decreased LES pressure, decreased acid clearance, increased reflux, and more severe esophagitis. […] Mucosal defense mechanisms may be overcome by prolonged exposure of the esophageal mucosa to a pH 4 that may lead to severe and complicated esophagitis. […] Esophageal mucosal inflammation may affect nerves and muscle that alter LES function and esophageal body motility. A vicious cycle of inflammation and impaired motility may cause progressive disease. […] Patients with GERD may develop endoscopically visible erosive esophagitis or endoscopically negative nonerosive or negative endoscopy reflux disease (NERD). In NERD, factors such as visceral hypersensitivity or more proximal reflux of acid or nonacid material may be important. Acid and inflammatory mediators may gain access to sensory pathways and produce symptoms either by a direct action on the nerves or by producing abnormal muscle contraction.

• #60 Gastroesophageal Reflux Disease: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/1999/0301/p1161.html

  Esophageal motility disorders and delayed gastric emptying may also be factors in the development of GERD. […] Other possible causal factors in GERD include delayed clearance of physiologic reflux by saliva, decreased secretion of bicarbonate by esophageal submucosal glands and attenuated ability of the cells lining the esophagus to resist acid injury.

• #61 Pathophysiology of gastroesophageal reflux disease : GI Motility online

  https://www.nature.com/gimo/contents/pt1/full/gimo21.html

  Hiatal hernia results from multiple mechanisms and is associated with a decreased LES pressure, decreased acid clearance, increased reflux, and more severe esophagitis. […] Mucosal defense mechanisms may be overcome by prolonged exposure of the esophageal mucosa to a pH 4 that may lead to severe and complicated esophagitis. […] Esophageal mucosal inflammation may affect nerves and muscle that alter LES function and esophageal body motility. A vicious cycle of inflammation and impaired motility may cause progressive disease. […] Patients with GERD may develop endoscopically visible erosive esophagitis or endoscopically negative nonerosive or negative endoscopy reflux disease (NERD). In NERD, factors such as visceral hypersensitivity or more proximal reflux of acid or nonacid material may be important. Acid and inflammatory mediators may gain access to sensory pathways and produce symptoms either by a direct action on the nerves or by producing abnormal muscle contraction.

• #62

  https://www.xiahepublishing.com/2994-8754/JTG-2023-00011

  The gastrointestinal microbiome remains an explosively increasing topic of study, assessing the potentially pivotal roles of the microbiome in maintaining health or causality in disease pathogenesis. Gastroesophageal reflux disease (GERD) has long been understood to be a result of direct acidic injury. However, emerging evidence suggests that GERD could also be caused by alterations in the esophageal microbiome, causing an induction of a submucosal inflammatory cytokine cascade, that has a retrograde effect on the luminal mucosa. […] The pathogenesis of GERD is influenced by a number of factors, characterized by an imbalance between harmful factors (reflux frequency, acidity of refluxate, esophageal mucosal contact time) and protective factors (esophageal acid clearance, mucosal integrity, lower esophageal sphincter pressure, anti-reflux barrier). Recent studies suggest that this multifactorial process is influenced by the esophageal microbiome, which can induce an immune response that eventually triggers inflammation and subsequent GERD.

• #63 Natural Products in the Management of Gastroesophageal Reflux Disease: Mechanisms, Efficacy, and Future Directions

  https://www.mdpi.com/2072-6643/17/6/1069

  The main component of stomach acid, hydrochloric acid (HCl), also plays a vital role in damaging the esophageal lining in GERD. […] HCl-induced damage causes an inflammatory response that aggravates tissue injury and contributes to the chronic nature of GERD. […] Furthermore, bile acids and pepsin exacerbate esophageal damage while chronic inflammation prolongs it. […] Recent research has indicated that imbalances in gut microbiota (dysbiosis) are another contributor to GERD. […] A detailed assessment of factors involved in the pathogenesis of GERD, including those aimed at restoring microbial balance, could help to identify possible therapeutic approaches that can reduce inflammation and protect the esophagus. […] The inflammatory response in GERD is driven by a cascade of biochemical events that include immune cell recruitment, cytokine release, and oxidative damage.

• #64

  https://www.xiahepublishing.com/2994-8754/JTG-2023-00011

  The microbiome also plays a role in gut motility, thereby possibly contributing to the pathogenesis of GERD. […] The GI microbiome includes various organisms across segments of the GI tract depending on their function and is subject to changes, as mentioned previously, to intrinsic and extrinsic influences. […] The presence of a bacterial biofilm can allow some bacteria, those not typically accustomed to increased pH, to thrive in certain locations. […] More recently, it has been shown that there is an inverse relationship between H. pylori and risk of GERD. […] These findings suggest that the H. pylori found in NERD may prevent esophageal-gastric mucosal erosion. […] Another study evaluated the esophageal microbiota in GERD as well as related complications of BE and esophageal adenocarcinoma.

• #65

  https://www.xiahepublishing.com/2994-8754/JTG-2023-00011

  We reviewed the current evidence regarding GERD and the GI microbiome. There is emerging data to suggest a paradigm shift in focus from GERD as a result of direct contact-mediated acidic injury towards an altered microbiome and induction of an inflammatory cytokine cascade. The effects of this microbiome cytokine cascade can have clinically significant consequences involving inflammatory changes in the esophagus.

• #66

  https://www.xiahepublishing.com/2994-8754/JTG-2023-00011

  The microbiome also plays a role in gut motility, thereby possibly contributing to the pathogenesis of GERD. […] The GI microbiome includes various organisms across segments of the GI tract depending on their function and is subject to changes, as mentioned previously, to intrinsic and extrinsic influences. […] The presence of a bacterial biofilm can allow some bacteria, those not typically accustomed to increased pH, to thrive in certain locations. […] More recently, it has been shown that there is an inverse relationship between H. pylori and risk of GERD. […] These findings suggest that the H. pylori found in NERD may prevent esophageal-gastric mucosal erosion. […] Another study evaluated the esophageal microbiota in GERD as well as related complications of BE and esophageal adenocarcinoma.

• #67

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2639970/

  The ability of the oesophageal mucosa to withstand injury is a determining factor in the development of GERD. […] When aggressive factors overwhelm the oesophageal defence, mucosal injury occurs. […] The exact aetiology of extra-oesophageal manifestations of GERD remains unknown. […] However, two main hypotheses, not necessarily mutually exclusive, have been proposed: direct contact of aspirated gastric refluxate with the upper airway and a vago-vagal reflex.

• #68 Pathogenesis and management of gastroesophageal reflux disease-associated cough: a narrative review – Zhang – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/74788/html

  Gastroesophageal reflux disease (GERD)-associated cough is defined as a special GERD with a predominant cough symptom and is a common cause of chronic cough. […] Although esophageal-tracheobronchial reflex mainly underlies the pathogenesis of GERD-associated cough, its counterpart-tracheobronchial-esophageal reflex might exist and initiate the cough due to reflux induced by upper respiratory tract infection through the signaling of transient receptor potential vanilloid 1 linking airway and esophagus. […] The presence of reflux-associated symptoms such as regurgitation and heartburn along with coughing suggests an association between cough and GERD, which is supported by the objective evidence of abnormal reflux as detected by reflux monitoring. […] Although there is no general consensus, esophageal reflux monitoring provides the main diagnostic criteria for GERD-associated cough.

• #69 Pathogenesis and management of gastroesophageal reflux disease-associated cough: a narrative review – Zhang – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/74788/html

  Despite that acid exposure time and symptom associated probability are useful and mostly employed reflux diagnostic criteria, they are imperfect and far from being the gold standard. […] Acid suppressive therapy has long been recommended as the first choice for GERD-associated cough. […] However, the overall benefits of proton pump inhibitors have been controversial and need to be further assessed, especially in patients with cough due to non-acid reflux. […] Neuromodulators have demonstrated potential therapeutic effects for refractory GERD-associated cough, for which anti-reflux surgery may also be a promising treatment option. […] Tracheobronchial-esophageal reflex might initiate reflux-induced cough provoked by the upper respiratory tract infection. […] It is necessary to optimize the current standards and to explore new criteria with higher diagnostic potency. […] Acid suppressive therapy is the first choice for GERD-associated cough, followed by neuromodulators and anti-reflux surgery for refractory GERD-associated cough.

• #70 Pathogenesis and management of gastroesophageal reflux disease-associated cough: a narrative review – Zhang – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/74788/html

  Despite that acid exposure time and symptom associated probability are useful and mostly employed reflux diagnostic criteria, they are imperfect and far from being the gold standard. […] Acid suppressive therapy has long been recommended as the first choice for GERD-associated cough. […] However, the overall benefits of proton pump inhibitors have been controversial and need to be further assessed, especially in patients with cough due to non-acid reflux. […] Neuromodulators have demonstrated potential therapeutic effects for refractory GERD-associated cough, for which anti-reflux surgery may also be a promising treatment option. […] Tracheobronchial-esophageal reflex might initiate reflux-induced cough provoked by the upper respiratory tract infection. […] It is necessary to optimize the current standards and to explore new criteria with higher diagnostic potency. […] Acid suppressive therapy is the first choice for GERD-associated cough, followed by neuromodulators and anti-reflux surgery for refractory GERD-associated cough.

• #71 Pathogenesis and management of gastroesophageal reflux disease-associated cough: a narrative review – Zhang – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/74788/html

  Despite that acid exposure time and symptom associated probability are useful and mostly employed reflux diagnostic criteria, they are imperfect and far from being the gold standard. […] Acid suppressive therapy has long been recommended as the first choice for GERD-associated cough. […] However, the overall benefits of proton pump inhibitors have been controversial and need to be further assessed, especially in patients with cough due to non-acid reflux. […] Neuromodulators have demonstrated potential therapeutic effects for refractory GERD-associated cough, for which anti-reflux surgery may also be a promising treatment option. […] Tracheobronchial-esophageal reflex might initiate reflux-induced cough provoked by the upper respiratory tract infection. […] It is necessary to optimize the current standards and to explore new criteria with higher diagnostic potency. […] Acid suppressive therapy is the first choice for GERD-associated cough, followed by neuromodulators and anti-reflux surgery for refractory GERD-associated cough.

• #72 Gastroesophageal Reflux Disease (GERD) – Gastrointestinal Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gastrointestinal-disorders/esophageal-and-swallowing-disorders/gastroesophageal-reflux-disease-gerd

  Incompetence of the lower esophageal sphincter allows reflux of gastric contents into the esophagus, causing burning pain. […] The presence of reflux implies lower esophageal sphincter (LES) incompetence, which may result from a generalized loss of intrinsic sphincter tone or from recurrent inappropriate transient relaxations (ie, unrelated to swallowing). […] Factors that contribute to the competence of the gastroesophageal junction include the angle of the cardioesophageal junction, the action of the diaphragm, gravity (ie, an upright position), and the patient’s age. […] Factors that may contribute to reflux include weight gain, fatty foods, caffeinated or carbonated beverages, alcohol, tobacco smoking, and medications. […] GERD may lead to esophagitis, esophageal ulcer, esophageal stricture, Barrett esophagus (replacement of normal squamous epithelium of the distal esophagus with metaplastic columnar epithelium during the healing phase of acute esophagitis), and esophageal adenocarcinoma.

• #73 Gastroesophageal Reflux Disease (GERD) – UChicago Medicine

  https://www.uchicagomedicine.org/conditions-services/esophageal-diseases/gastroesophageal-reflux-disease

  Gastrointestinal reflux disease (GERD) is more than just heartburn. Untreated, GERD can develop into more serious conditions, including cancer for a small percentage of individuals. […] A one-way valve called the lower esophageal sphincter (LES) allows food to pass into your stomach and prevents stomach acid from flowing back up into the esophagus. When this valve is weakened and not functioning properly, gastric juice comes up from the stomach and back into the esophagus causing irritation and inflammation (esophagitis). Over time, this can damage to the lining of the esophagus. Nearly half of patients with GERD will develop esophagitis, and up to 15 percent of patients with GERD may develop a pre-cancerous condition called Barretts esophagus. A small percentage of people with Barretts esophagus will progress to esophageal adenocarcinoma a form of cancer in the esophagus.

• #74 Gastroesophageal Reflux Disease (GERD) | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/cancer-care/patient-education/gastroesophageal-reflux-disease-gerd

  GERD is a disorder where the contents of your stomach flow back into your esophagus. […] GERD can cause esophagitis (ee-SAH-fuh-JY-tis). This when the lining in your esophagus is inflamed (red and swollen). If you do not treat esophagitis, it can cause ulcers (sores), bleeding, and narrowing in your esophagus. It may also increase your risk for esophageal cancer. […] GERD can be caused by many things, including: Eating large meals. Eating and drinking large amounts of fried or fatty foods, spicy foods, citrus fruits, chocolate, mint, tomatoes, and caffeinated drinks. Exercising after a meal. Lying down, especially after meals. This can make it easier to regurgitate food. Smoking. Drinking alcohol. Having a hiatal hernia. Pregnancy. Obesity. Pressure on your abdomen. […] The goal of treatment for GERD is to reduce your symptoms. Most people feel better with medicine and lifestyle changes.

• #75 Gastroesophageal Reflux Disease (GERD) – UChicago Medicine

  https://www.uchicagomedicine.org/conditions-services/esophageal-diseases/gastroesophageal-reflux-disease

  GERD can lead to more serious conditions if not diagnosed and treated properly. If you have experienced GERD for a number of years, it is important to have your esophagus checked for changes. […] A number of patients with GERD may be appropriate candidates for surgical treatment with an anti-reflux procedure. This procedure tightens the valve located between the stomach and the esophagus, called the lower esophageal sphincter, which prevents the stomach contents and acid from refluxing back into the esophagus. Unlike medications that provide only symptomatic heartburn relief, anti-reflux surgery can stop GERD symptoms for most patients, including regurgitation, trouble swallowing and voice changes. […] If you have GERD, you have a higher risk for Barretts esophagus. People with this condition can develop a rare type of esophageal cancer. Although the overall risk for esophageal cancer is extremely low, we recommend getting a screening test called a surveillance esophagogastroduodenoscopy (EGD) every three to five years if you have GERD.

• #76

  https://journals.lww.com/md-journal/fulltext/2016/07050/association_between_gastroesophageal_reflux.46.aspx

  In this study, we aimed to determine the association between gastroesophageal reflux disease (GERD) and subsequent coronary heart disease (CHD) development, if any, and to evaluate whether longer use of proton pump inhibitors (PPIs) increases the risk of CHD. […] The GERD patients had a greater probability of CHD than the cohort without GERD did (log-rank test, P 0.001 and 11.8 vs 6.5 per 1000 person-years). […] Our population-based cohort study results indicate that GERD was associated with an increased risk of developing CHD, and that PPI use for more than 1 year might increase the risk of CHD. […] A coexisting relationship between GERD and CHD has been widely accepted, though the mechanism underlying the relationship is complex. […] Our study results indicate that GERD patients have a greater number of comorbidities than do non-GERD patients, and indicate that GERD is associated with hypertension, diabetes, hyperlipidemia, alcohol-related illness, stroke, obesity, COPD, asthma, biliary stone, anxiety, depression, chronic kidney disease, and cirrhosis.

• #77

  https://journals.lww.com/md-journal/fulltext/2016/07050/association_between_gastroesophageal_reflux.46.aspx

  Our results indicate that GERD is associated with subsequent CHD development after adjustment for age, sex, hypertension, diabetes, hyperlipidemia, alcohol-related illness, stroke, COPD, asthma, biliary stones, anxiety, depression, chronic kidney disease, and cirrhosis. […] Our results suggest that PPI use might have a detrimental effect on CHD, because the risk of CHD among the patients treated for more than 1 year was greater than that of patients treated for 1 year. […] However, we still could not ascertain whether there is a causal relationship between GERD and CHD or whether the duration of PPI use imposes the deteriorating defect on CHD development in a dose-response effect. […] Our study also used a longitudinal rather than cross-sectional approach to evaluate the temporal and casual associations between GERD and CHD. […] In conclusion, the results from our population-based cohort study indicate that GERD was associated with an increased risk of developing CHD, and PPI usage for more than 1 year might increase the risk of CHD.

• #78

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2639970/

  While the pathogenesis of oesophageal symptoms is now well known, the mechanisms underlying extra-oesophageal airway manifestations are still poorly understood. […] In conclusion, gastro-oesophageal reflux disease can be considered as the result of a complex interplay of factors, all promoting the contact of gastric acidic contents with the oesophageal mucosa, leading to different degrees of oesophageal damage. […] As in other acid-related diseases, such as duodenal and gastric ulcer disease, GERD is thought to develop when aggressive factors, potentially harmful to the oesophagus, overcome protective mechanisms such as the oesophago-gastric junction barrier, oesophageal acid clearance and mucosal resistance, which normally contribute to maintain a physiologically balanced state. […] Therefore, a crucial role, in the pathogenesis of GERD, is played by contact with the oesophageal mucosa of refluxate, which can be composed of acid, pepsin, bile and duodenal contents.

• #79 Pathophysiology of gastroesophageal reflux disease : GI Motility online

  https://www.nature.com/gimo/contents/pt1/full/gimo21.html

  The factors generally accepted as important for the development of gastroesophageal reflux disease (GERD) have been well documented. Abnormality of any one of these factors holds the potential to disturb the normal equilibrium. These factors include gastric acid and other refluxed contents; delayed gastric emptying; structural and physiologic antireflux mechanisms at the gastroesophageal region; transient lower esophageal sphincter relaxation (TLESR); esophageal clearance mechanisms; ingested irritants; ingested substances that alter gastric, lower esophageal sphincter (LES), or esophageal motor function; mucosal integrity and defense mechanisms; visceral hypersensitivity; and genetic factors. […] Despite the many factors that operate, four main fundamental factors stand out as most important: (1) gastric acid; (2) the structural integrity, function, and competence of the LES that either prevent or allow reflux; (3) the esophageal mucosal defense mechanisms that are primarily called into play when there is excess exposure of the mucosa to gastric acid; and (4) the sensory mechanisms that speak to symptoms. That is, an incompetent gastroesophageal reflux mechanism allows abnormal amounts of gastric acid to enter the esophagus, where the acid burden causes mucosal damage and/or symptoms.

• #80 The Pathophysiologic Basis for Epidemiologic Trends in Gastroesophageal Reflux Disease | Abdominal Key

  https://abdominalkey.com/the-pathophysiologic-basis-for-epidemiologic-trends-in-gastroesophageal-reflux-disease/

  Gastroesophageal reflux disease (GERD) is defined by either subjective complaints indicative of problematic gastroesophageal reflux or objective complications directly attributable to reflux. […] The cause of the increased GERD prevalence is debated and likely multifactorial. Epidemiologic data indicate, however, that possible contributing factors include increasing longevity, rising obesity rates, greater consumption of medications affecting esophageal function, and potentially changing prevalence rates of Helicobacter pylori infection. […] Gastroesophageal reflux is a normal physiologic event, but excessive exposure of esophageal or supraesophageal epithelium to gastric refluxate resulting in either mucosal injury or related symptoms is the fundamental abnormality in GERD. […] The genesis of reflux injury and reflux symptoms are not the same but each relates to some combination on pathophysiologic factors leading to an excessive number of gastroesophageal reflux events, impaired clearance of refluxate from the esophagus, increased acidity of the refluxed gastric juice, or increased sensitivity of the esophageal or supraesophageal mucosa to that refluxate.

• #81 Current Advancement on the Dynamic Mechanism of Gastroesophageal Reflux Disease

  https://www.ijbs.com/v17p4154.htm

  Gastroesophageal reflux disease (GERD) is a common clinical disease associated with upper gastrointestinal motility disorders. However, the mechanism of GERD has not been fully elucidated due to its complex pathogenesis, and this had led to unsatisfactory therapeutic outcomes. Currently, the occurrence and development of GERD involve multiple factors. Its pathogenesis is mainly thought to be related to factors, such as lower esophageal sphincter pressure, transient lower esophageal sphincter relaxation, crural diaphragmatic dysfunction, hiatus hernia, and impaired esophageal clearance. Therefore, explaining the pathogenesis of GERD more clearly and systematically, exploring potential and effective therapeutic targets, and choosing the best treatment methods have gradually become the focus of scholars’ attention.

• #82 Gastroesophageal Reflux Disease (GERD) | SJFM

  https://sanjosefuncmed.com/common-stomach-disorders/

  Treating gastroesophageal reflux disease with profound acid inhibition will never be ideal because acid secretion is not the primary underlying defect. Acid secretion is normal in most patients with reflux disease and acid inhibitory therapy makes it abnormally low. It is never ideal to treat one abnormality by creating another, as was the case for many years with management of ulcer disease before the discovery of H. pylori infection. The pathophysiology of acid reflux concerns the dysfunction of the gastroesophageal barrier and research needs to refocus on ways of restoring its competence rather than merely suppressing gastric acid secretion.

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