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. […] As a result, reflux of acid, bile, pepsin and pancreatic enzymes occurs, leading to oesophageal mucosal injury. […] 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.

• #1 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. […] Currently, the pathogenesis of GERD is generally believed to be related to reduction in the pressure of the lower esophageal sphincter (LES), transient and excessive lower esophageal sphincter relaxation (TLESR), hiatal hernia, esophageal clearance dysfunction, acid pockets, esophageal hypersensitivity, and mucosal barrier damage.

• #1 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.

• #1 Pediatric Gastroesophageal Reflux: Practice Essentials, Background, Etiology and Pathophysiology

  https://emedicine.medscape.com/article/930029-overview

  In pediatric gastroesophageal reflux disease (GERD), immaturity of lower esophageal sphincter function is manifested by frequent transient lower esophageal relaxations, which result in retrograde flow of gastric contents into the esophagus. […] The causes and risk factors for gastroesophageal reflux in children are frequently multifactorial. […] Transient lower esophageal sphincter relaxation (tLESR) – This is currently believed to be the main mechanism of gastroesophageal reflux, accounting for 94% of reflux episodes in children and adults; poor basal LES tone was previously thought to be a cause. […] The major mechanism in infants and children has now been demonstrated to involve increases in tLESRs. Factors that may promote gastroesophageal reflux during tLESRs include increased intragastric liquid volume and supine and „slumped” seated positioning. […] Reflux is facilitated when an increase in intraabdominal pressure occurs. In some cases, and particularly in children with neurodevelopmental disabilities, the presence of a chronically lax LES associated with decreased or even absent sphincter tone results in severe gastroesophageal reflux.

• #1 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). […] 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. […] 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.

• #1 Pathophysiology and treatment options for gastroesophageal reflux disease: looking beyond acid

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9792178/

  Gastroesophageal reflux disease (GERD) is a disorder due to the retrograde flow of refluxate into the esophagus. Although GERD is a common clinical diagnosis, its pathogenesis is quite complex. […] The pathogenesis of GERD involves an interplay of chemical, mechanical, psychologic, and neurologic mechanisms, which contribute to symptom presentation, diagnosis, and treatment. As such, GERD should be approached as a disorder beyond acid. […] While classically considered a disease of excess acid, up to 50% of patients with GERD experience little to no relief with pharmacologic acid suppression. […] As more is uncovered regarding the pathophysiology and etiologies underlying GERD, it is evident that the development of reflux disease extends beyond acidity of the refluxate. […] The mechanism by which acid leads to mucosal injury has been well studied.

• #1 Surprising mechanism of acid reflux damage identified

  https://medicalxpress.com/news/2016-05-mechanism-acid-reflux.html

  The „acid” in „acid reflux” may not be the direct cause of damage to the esophagus as previously suspected, according to researchers at UT Southwestern Medical Center and Dallas VA Medical Center. […] For more than 80 years, it has been assumed that stomach acid backing up through the esophagus damaged the lining of the esophagus by causing chemical burns, but their research suggests that the damage in patients with gastroesophageal reflux disease (GERD) actually occurs through an inflammatory response prompted by the secretion of proteins called cytokines. […] Importantly, the changes that re-occurred were not consistent with chemical burns. Rather, the findings supported the new idea that refluxed stomach acid stimulates the esophagus to make small proteins called cytokines, which then sets up the process of inflammation.

• #1 A narrative review of the prevalence of gastroesophageal reflux disease (GERD) – Boulton – Annals of Esophagus

  https://aoe.amegroups.org/article/view/6041/html

  A major role in the pathogenesis of GERD is the abnormal incidence of reflux, which contains bile, pepsin, acid and duodenal contents coming into contact with esophageal mucosa resulting in troublesome symptoms. […] The duration of acid and its exposure to the esophagus increases the risk of complications. This complication can manifest into Barretts esophagus, which is considered as a pre-cancerous metaplasia and can also cause mucosal damage, leading to the development of esophageal adenocarcinoma. […] Biliary acids or pancreatic enzymes within the refluxed material also add to the pathogenesis of GERD. […] Today it is understood that the major motor component involves the stomach, gastroesophageal junction, nervous structures, the esophagus and its sphincters. […] Within GERD patients the transient relaxation of the lower sphincter causes a reflux episode to occur. Therefore health issues such as a hiatal hernia that cause a delay in gastric emptying and decrease pressure in the lower sphincter, give rise to a GERD diagnosis.

• #1 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 clinical manifestations and diagnosis of this disorder are discussed separately. […] MECHANISMS OF GASTROESOPHAGEAL REFLUX DISEASE […] 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) (algorithm 1). 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. Although the same can be said of symptom severity, it is complicated by the added determinant of esophageal hypersensitivity. […] 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.

• #1 Heartburn and esophageal pain : GI Motility online

  https://www.nature.com/gimo/contents/pt1/full/gimo75.html

  Esophageal pain manifests as symptoms of heartburn and or chest pain. […] Esophageal dysmotility may also induce symptoms of heartburn and chest pain. […] Acid-induced esophageal pain is likely to be mediated by vanilloid receptor 1 (VR1) and by anion-sensing ion channels (ASICs). […] Visceral hypersensitivity has been implicated in the pathogenesis of esophageal pain. […] Distention of the esophagus results in secondary peristalsis at lower levels of distention and pain at higher levels of distention. […] Distention of the esophagus is generally thought to cause esophageal pain, but several studies show that the majority of subjects actually experience heartburn with esophageal distention. […] The observation that patients may get relief of their esophageal pain with smooth muscle relaxants (nitroglycerine) suggests that smooth muscle contraction may indeed elicit pain.

• #1 Can Stress Trigger Heartburn or Acid Reflux? | PEPCID®

  https://www.pepcid.com/understanding-heartburn/heartburn-and-stress

  Yes, stress can be a heartburn trigger. When too many things pile up at work, school, or home, or you experience a big life change, heartburn symptoms may worsen. […] Stress may also be connected to the conditions that cause heartburn: acid reflux and gastroesophageal reflux disease (GERD). Acid reflux occurs when stomach contents flow backward into the esophagus, and GERD is the name for a condition in which acid reflux occurs frequently. Acid reflux and GERD can both cause heartburn and may both be influenced by stress levels. […] Researchers are still learning about how stress and heartburn are connected. They know that the brain and the digestive system communicate with each other through a system called the brain-gut axis. When the brain is feeling stressed, the brain-gut microbiota are disrupted and release various substances that can affect the way the digestive organs work. This process may slow down digestion, causing food to sit in the stomach longer and leading to a higher chance that stomach juices flow into the esophagus.

• #1 Association Between Psychosocial Disorders and Gastroesophageal Reflux Disease: A Systematic Review and Meta-analysis

  https://www.jnmjournal.org/journal/view.html?spage=212&volume=28&number=2

  GERD mainly refers to the reflux of stomach and duodenum contents to the esophagus, which, in turn, causes acid reflux, heartburn, and other symptoms. […] Recent studies have suggested that the pathogenesis of erosive gastroesophageal reflux disease is mainly due to excessive acid exposure and subsequent mucosal damage caused by reflux. However, for NERD without mucosal damage under gastroscopy, the pathogenesis is mainly due to psychological stress from esophageal hypersensitivity, epithelial permeability, and dilation of intercellular space causing changes in intercellular pH and/or osmotic pressure, leading to pain. […] Studies have shown that the poor efficacy of proton pump inhibitors in patients with GERD may be caused by psychological factors. […] This meta-analysis of 9 observational studies provided evidence of an increased OR for GERD of 2.57 with the occurrence of psychosocial disorders (95% CI, 1.87-3.54). Individuals with GERD had a 2.63-fold higher risk of depression (OR, 2.63; 95% CI, 1.75-3.95) and a 3.43-fold higher risk of anxiety (OR, 3.43; 95% CI, 1.95-6.03).

• #1 Gastroesophageal reflux disease – Wikipedia

  https://en.wikipedia.org/wiki/Gastroesophageal_reflux_disease

  Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is a chronic upper gastrointestinal disease in which stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/or complications. Symptoms include dental corrosion, dysphagia, heartburn, odynophagia, regurgitation, non-cardiac chest pain, extraesophageal symptoms such as chronic cough, hoarseness, reflux-induced laryngitis, or asthma. In the long term, and when not treated, complications such as esophagitis, esophageal stricture, and Barrett’s esophagus may arise. […] Acid reflux is due to poor closure of the lower esophageal sphincter, which is at the junction between the stomach and the esophagus. […] The etiology of GERD appears to include the reflux of bile from the stomach into the esophagus leading to the production of reactive oxygen species and oxidative stress and then inflammation and induction of DNA damage. […] In experimental models of GERD it was found that Lactobacilli facilitate the repair of such DNA damage indicating that administration of these potentially probiotic bacteria may be useful in patients suffering with GERD for preventing progression to Barretts esophagus and esophageal adenocarcinoma.

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

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

  Gastroesophageal reflux disease (GERD) is thought to have a multifactorial etiology rather than a single cause. Contributing factors include the caustic materials that are refluxed, a breakdown in the defense mechanisms of the esophagus and a functional abnormality that results in reflux. […] Acidic gastric material is undoubtedly the primary offending agent in the development of GERD, with duration of exposure being a key factor. […] The role of bile acids from the duodenum is also being investigated. As many as 60 percent of patients with GERD reflux both gastric and duodenal juices. […] Transient relaxation of this sphincter may occur more often in patients with GERD. […] 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.

• #1 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.

• #1

  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.

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

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

  The primary pathophysiological mechanisms of GERD are anti-reflux barrier function weakening and impaired esophageal clearance function. […] The LES is the most important structure of the anti-reflux barrier at the esophagogastric junction. […] Reflux occurs when the resting pressure of the LES is abnormally low, resulting in a gastric pressure that is higher than the esophageal pressure. […] With an in-depth study of the pathogenesis of GERD, it is now generally believed that TLESR is the main cause of gastroesophageal reflux. […] The mechanism of GERD caused by TLESR may be related to changes in EGJ compliance and the increase in EGJ pressure gradient. […] The abnormal anatomy and function of the crural diaphragm is another important factor that causes gastroesophageal reflux. […] 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.

• #2 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. […] In patients with GERD, several abnormalities of contraction have been described. […] 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. […] Esophageal acid testing is considered a „gold standard” for diagnosing GERD.

• #2 Pathophysiology of Gastroesophageal Reflux Disease : Bariatric Times

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

  Pathologic GERD occurs when there is a failure of the normal physiologic mechanisms. […] Transient LES relaxations (TLESR) are reflux events independent of a swallow. […] Hiatal hernias disrupt the anatomical antireflux barrier. […] The presence of a hiatal hernia also leads to decreased esophageal clearance and causes gastric acid trapping in the hernia sac. […] Decreased esophageal clearance can occur separate from a hiatal hernia and lead to a continuous cycle of inflammation. […] Additional factors that contribute to the pathophysiology of GERD include delayed gastric emptying and obesity. […] The pathophysiology of GERD remains a dynamic area of research. The antireflux barrier is currently a key component of GERD.

• #2

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

  Impaired oesophageal clearance is responsible for prolonged acid exposure of the mucosa. […] 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. […] The mucosal defensive factors play an important role against development of gastro-oesophageal reflux disease, by neutralizing the backdiffusion of hydrogen ion into the oesophageal tissue. […] 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.

• #2 Pathophysiology and treatment options for gastroesophageal reflux disease: looking beyond acid

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9792178/

  The mechanism by which each component affects the esophageal mucosa is distinct, and thus the etiology of GERD may be specific to the predominant refluxate component and its mechanism of action. […] Although acid has been identified as one of the major mediators of cellular injury in GERD, not all cases of GERD are characterized by acidic pH of the refluxate. […] The relationship between bile and gastric acids in GERD pathophysiology may be less direct. […] Overall, it is evident that bile acids may play a major role in the pathogenesis of GERD and thus can serve as a potential diagnostic biomarker as well as a therapeutic target. […] The role of pepsin in mucosal injury of the esophagus is less well defined. […] Overall, pepsin as a component of gastric refluxate can cause epithelial damage and cell death by various mechanisms.

• #2 Heartburn pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Heartburn_pathophysiology

  Heartburn is the burning pain caused by the reflux of gastric acid and pepsin from the stomach into the esophagus. […] These substances enter the esophagus due to a dysfunctional lower esophagus sphincter, which in normal conditions should now allow the occurrence of such reflux. […] This can happen due to many causes such as hiatal hernia, use of medications which causes relaxation of the lower esophagus sphincter or due to abnormal relaxation or weakening of the lower esophagus sphincter which causes the gastroesophageal reflux disease. […] The gastric acid and the pepsin damages the epithelium and causes an inflammatory response mediated by IL-8 and IL-1B. These cytokines stimulate inflammation and sensitizes the peripheral nerves in the mucosa which mediates the pain. It is believed that the release of such cytokines is mediated by an increased production of PGE2 and ATP by the epithelium.[1] […] With the most recent research findings, it is believed that the gastric acid does not directly cause heartburn, but causes it using a myriad of inflammatory mechanisms which are being elucidated and may be targets of new therapeutic drugs in the future.[1]

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

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

  A large number of previous studies have confirmed that gastroesophageal reflux leads to the destruction of esophageal epithelial barrier function; however, the specific mechanism is still not completely clear. Gastroesophageal reflux leads to the destruction of esophageal epithelial barrier function by regulating the expression and distribution of tight junction proteins (such as Occludin, Cldn1, Cldn3 and Cldn4), reducing the number of desmosomes, and the direct hydrolysis of adhesive junction proteins (such as E-cadherin). This is manifested by the widening of intercellular spaces (ICS) and the reduction of trans-epithelial electrical resistance (TEER). In addition, this is accompanied by an inflammatory response in the mucosal epithelium. […] 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.

• #2 Can Stress Trigger Heartburn or Acid Reflux? | PEPCID®

  https://www.pepcid.com/understanding-heartburn/heartburn-and-stress

  Stress may make people more aware of their heartburn pain, and for some, stress can make some more likely to engage in behaviors that may trigger heartburn, such as eating fattier foods or smoking cigarettes. […] There are multiple unhealthy lifestyle factors that can lead to heartburn. For example, drinking alcohol, smoking, or using tobacco products can also increase acid reflux.

• #2 Association Between Psychosocial Disorders and Gastroesophageal Reflux Disease: A Systematic Review and Meta-analysis

  https://www.jnmjournal.org/journal/view.html?spage=212&volume=28&number=2

  We identified several possible explanations for the increased risk of psychosocial disorders caused by GERD. First, acid reflux events disrupt sleep architecture. […] Second, the abnormal expression of inflammatory cytokines in the esophageal mucosa, such as interleukin IL-6, IL-8, IL-1beta, interferon-gamma, and tumor necrosis factor-alpha (TNF-) may also play a role. […] Psychosocial disorders may also increase the risk of developing GERD. Psychological disorders can regulate the sensation of esophageal pain. […] The specific mechanisms are as follows. First, the tight junctions of the esophageal epithelium of psychologically stressed rats are destroyed, thereby weakening or reducing the barrier function of the esophageal mucosa. […] Second, mental states such as anxiety may impair esophageal motor function and cause esophageal motility disorders by reducing the pressure of the lower esophageal sphincter.

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

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

  When discussing the mechanisms for GERD, the issue of hiatal hernia must be addressed. Hiatal hernias can be encountered frequently in patients with reflux disease; however, it has been well proven that not all patients with hiatal hernias have symptomatic reflux. […] 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.

• #2 A narrative review of the prevalence of gastroesophageal reflux disease (GERD) – Boulton – Annals of Esophagus

  https://aoe.amegroups.org/article/view/6041/html

  Over time epidemiological data has associated GERD with obesity, this is an important finding as the obesity rates worldwide have tripled since 1975 affecting both adults and children. […] Other potential risk factors for GERD include increasing age, genetics, pregnancy and dietary/lifestyle choices, alcohol consumption and cigarette smoking. […] The progression of GERD has increased since 1995, this is due to the dietary patterns of the younger generations and a worldwide increase of overweight or morbid obesity in both the adolescent and paediatric population.

• #2 Gastroesophageal reflux disease (GERD) – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/gerd/symptoms-causes/syc-20361940

  Over time, long-lasting inflammation in the esophagus can cause: Inflammation of the tissue in the esophagus, known as esophagitis. Stomach acid can break down tissue in the esophagus. This can cause inflammation, bleeding and sometimes an open sore, called an ulcer. Esophagitis can cause pain and make swallowing difficult. […] Narrowing of the esophagus, called an esophageal stricture. Damage to the lower esophagus from stomach acid causes scar tissue to form. The scar tissue narrows the food pathway, leading to problems with swallowing. […] Precancerous changes to the esophagus, known as Barrett esophagus. Damage from acid can cause changes in the tissue lining the lower esophagus. These changes are associated with an increased risk of esophageal cancer.

• #2 Refractory Gastroesophageal Reflux Disease: Diagnosis and Management

  https://www.jnmjournal.org/view.html?uid=1890&vmd=Full

  Proper diagnosis and management of refractory GERD is critical to mitigate undesirable long-term complications such as strictures, Barretts esophagus, and esophageal adenocarcinoma. This review outlines the diagnostic workup of patients presenting with refractory GERD symptoms, describes the distinction between unproven and proven GERD, and provides a comprehensive review of the current treatment strategies available for the management of refractory GERD. […] The defining features of GERD include an abnormal reflux monitoring study and/or findings on upper endoscopy that corroborate pathologic acid exposure, such as EE or Barretts esophagus. Unproven GERD indicates that the patient either has not undergone testing to define features that identify objective GERD, or has negative testing while off anti-secretory therapy. In contrast, proven GERD implies that objective evidence of GERD has been previously demonstrated on either endoscopy or ambulatory reflux monitoring. Persisting symptoms while on treatment in patients with a history of proven GERD should be referred to as refractory symptoms rather than refractory GERD. Given that symptoms do not necessarily correlate with pathologic reflux, further evaluation can define whether the patient truly has refractory GERD versus esophageal hypersensitivity and/or functional heartburn.

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

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

  The mechanism through which HH leads to GERD may also be related to the presence of gastric contents in the hernia sac and reflux of gastric contents when the LES relaxes. […] Esophageal clearance capacity includes the neutralization of reflux by saliva, weight of food itself, and protrusion of esophageal peristalsis. […] Studies have confirmed that the incidence of IEM in the esophageal body of patients with GERD is 63.95%, and IEM leads to delayed esophageal acid clearance in these patients. […] The presence of preoperative IEM should not be a contraindication for Nissen fundoplication, and the key to the optimal outcome of laparoscopic anti-reflux surgery is to carefully evaluate the patient’s condition based on the objective data, so as to adjust the surgical approach to provide effective reflux control and improve esophageal clearance.

• #3 Pathophysiology and treatment options for gastroesophageal reflux disease: looking beyond acid

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9792178/

  The esophageal mucosa consists of nonkeratinized squamous epithelium divided into three functionally distinct layers, including the proliferating stratum basalis, a metabolically active stratum spinosum, and an enucleated stratum corneum. […] The presence of DIS on electron microscopy has been described as a sensitive marker for esophageal damage due to GERD. […] The role of neuronal afferents in the symptom presentation has become of particular interest as it relates to nonerosive GERD. […] Many advances have been made in recognizing reflux hypersensitivity, as it is now identified as one of the five functional esophageal disorders based on the Rome IV criteria. […] Impaired anterograde flow of esophageal and gastric contents can lead to increased exposure time of the esophageal mucosa to the refluxate.

• #3 Association Between Psychosocial Disorders and Gastroesophageal Reflux Disease: A Systematic Review and Meta-analysis

  https://www.jnmjournal.org/journal/view.html?spage=212&volume=28&number=2

  Third, psychological disorders can affect esophageal sensitivity through peripheral and central mechanisms; that is, peripheral sensitization and central sensitization. […] Fourth, psychological disorders increase the esophageal mucosal perception of stimuli in the esophagus through the interaction of the brain-gut axis, leading to small stimuli that can also cause pain and heartburn. […] In conclusion, the results of our meta-analysis showed a significant positive association between psychosocial disorders and GERD. GERD patients are more likely to develop psychosocial disorders than healthy people; at the same time, psychosocial disorders can also increase the risk of GERD. There was a positive interaction between the 2 variables.

• #3

  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. […] 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.

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

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

  The mechanism by which a high BMI increases esophageal acid exposure is not completely understood. Increased intragastric pressure and gastroesophageal pressure gradient, incompetence of the lower esophageal sphincter (LES), and increased frequency of transient LES relaxations may all play a role in the pathophysiology of GERD in patients who are morbidly obese.

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

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

  The esophageal mucosal barrier is mainly composed of esophageal mucosal epithelial cells. The defensive barrier structure of esophageal epithelium is mainly composed of the apical junctional complexes (AJCs) of esophageal keratinocytes and epithelial cell membrane, which is responsible for preventing luminal ions (mainly hydrogen ions) and small molecules from entering the submucosa. […] 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.

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

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

  About 30% to 40% of reflux is most likely hereditary, according to several twin and family studies. An inherited risk exists in many cases of GERD, possibly because of inherited muscular or structural problems in the stomach or esophagus. […] The role of Helicobacter pylori in causing GERD is less clear. It may depend on what portion of the stomach is involved. […] Nonsteroidal anti-inflammatory drugs (NSAIDs) may also cause GERD or increase its severity in people who already have it. […] Many other drugs can increase the risk for GERD, including calcium channel blockers, anticholinergics, beta-adrenergic agonists, dopamine agonists, bisphosphonates, sedatives, antibiotics, potassium, and iron pills. […] The standard surgical treatment for GERD is fundoplication. The goal of this procedure is to increase LES pressure and prevent acid backup (reflux). […] Fundoplication is recommended for people whose condition includes esophagitis (inflamed esophagus), symptoms that persist or come back in spite of antireflux drug treatment, strictures (or narrowing) in the esophagus, and failure to gain or maintain weight (in children).

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

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

  NF-B can directly regulate tight junction protein expression and impair epithelial barrier function by relaxing tight junctions. Previous animal studies have also shown that NF-B pathway inhibitors can significantly prevent destruction of the reflux-induced esophageal mucosal barrier. […] In conclusion, we propose that the reduction of esophageal mucosal barrier function induced by gastroesophageal reflux may be the result of a combination of direct chemical destruction and a NF-B-mediated inflammation process.

Zobacz więcej