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.

• #1 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.

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

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

  It is extremely important to identify which of these components is defective so that an effective therapy can be applied. […] Proper esophageal clearance is an extremely important factor in preventing mucosal injury. Esophageal clearance must be able to neutralize the acid refluxed through the lower esophageal sphincter. […] Abnormal peristalsis can cause inefficient and delayed acid clearance. […] The lower esophageal sphincter (LES) is defined by manometry as a zone of elevated intraluminal pressure at the esophagogastric junction. […] LES dysfunction occurs via one of several mechanisms: transient relaxation of the LES (most common mechanism), permanent LES relaxation, and transient increase of intra-abdominal pressure that overcomes the LES pressure. […] 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.

• #1 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 is defined as lower esophageal sphincter relaxation that is induced spontaneously without swallowing. […] 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.

• #1 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. […] Mittal et al reported a feasibility study in which LES lift seen on HRM was a possible surrogate marker for LMC. […] 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. […] TLESR usually terminates by esophageal contractions, including PP and secondary contractions. […] Delayed esophageal emptying of refluxate may worsen the esophageal environment after gastroesophageal reflux. […] In conclusion, TLESR events did not differ between the GERD and control groups.

• #1 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. […] The mechanism of GERD caused by TLESR may be related to changes in EGJ compliance and the increase in EGJ pressure gradient. […] The EGJ pressure is mainly composed of the crural diaphragm tension and LES pressure. […] A previous study found that at rest, the crural diaphragm tension of patients with GERD is significantly lower than that of healthy participants. […] 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. […] Studies have confirmed that there are two high-pressure bands in patients with HH: one is at the level of the LES and the other is at the level of the crural diaphragm, with no overlap between these two bands.

• #1 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.

• #1 Surprising mechanism of acid reflux damage identified by researchers | ScienceDaily

  https://www.sciencedaily.com/releases/2016/05/160517191818.htm

  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. […] 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. […] 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. […] This study challenges some of the long-held beliefs about how gastroesophageal reflux damages the esophageal mucosa in patients with gastroesophageal reflux disease. […] Furthermore, our study should open up new avenues for novel GERD treatments.

• #1 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. […] Heartburn is a condition in which the acidic stomach contents back up into the esophagus, causing pain in the chest area. This reflux usually occurs because the sphincter muscle between the esophagus and stomach is weakened. […] Continuous irritation of the esophagus lining, as in severe GERD, is a risk factor for developing esophageal cancer. […] 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.

• #1 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. […] 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. […] When mucosal damage occurs (esophagitis), a vicious cycle can ensue to accentuate and maintain the GERD.

• #1 Heartburn – Wikipedia

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

  However, in gastroesophageal reflux disease (GERD), one of the earliest signs of damage is the development of dilated intercellular spaces (DISs) in the esophageal lining. These spaces weaken the protective barrier, allowing acid and other substances to seep in. […] This triggers pain-sensitive nerves, which send signals to the brain and cause the sensation of heartburn. […] Esophageal hypersensitivity plays a major role in heartburn, especially in those with GERD who have normal acid levels. […] Anxiety and stress can further heighten heartburn perception, both through brain mechanisms and possibly by weakening the esophageal lining (dilated intercellular spaces).

• #1 Heartburn pathophysiology – wikidoc

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

  The sensation of heartburn is caused by exposure of the lower esophagus to the acidic contents of the stomach. Normally, the lower esophageal sphincter (LES) separating the stomach from the esophagus is supposed to contract to prevent this situation. If the sphincter relaxes for any reason (as normally occurs during swallowing), stomach contents, mixed with gastric acid, can return into the esophagus. This return is also known as reflux, and may progress to gastroesophageal reflux disease (GERD) if it occurs frequently. If this is the case, the gastric acid and pepsin now located in the esophagus can injure the tight junction proteins in the esophageal epithelium. This results in increased paracellular permeability and dilated intercellular space and edema in the submucosa, which is amplified by an immunological mechanism mediated by inflammatory cytokines.[1]

• #1 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]

• #1 Functional heartburn: Symptoms, causes, and treatment

  https://www.medicalnewstoday.com/articles/functional-heartburn

  Esophageal hypersensitivity may be the primary factor. In functional heartburn, the esophagus may be overly sensitive to stimuli, leading to the sensation of heartburn even in the absence of significant acid reflux or esophageal damage. […] Unlike typical GERD, functional heartburn does not show a clear relationship with acid reflux events. Symptoms can occur even in the absence of acid reflux. […] In functional heartburn, the esophagus usually appears normal. […] Normal acid levels can indicate functional heartburn. […] The primary symptom is a burning sensation in the chest, often resembling typical heartburn, yet without a clear association with acid reflux. […] Functional heartburn is typically a chronic condition. While it does not cause physical damage to the esophagus like traditional GERD, it can persist over time and may require ongoing management. […] Unlike GERD, which can sometimes lead to complications such as Barrett’s esophagus and an increased risk of esophageal cancer, functional heartburn does not carry these risks, as it does not involve chronic acid damage to the esophagus.

• #1 The pathogenesis of heartburn in nonerosive reflux disease: a unifying hypothesis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/15765412/

  Heartburn is a symptom complex that has traditionally been accepted as an acid-mediated event and a reliable indicator of gastroesophageal reflux disease. […] Recently, however, these concepts have been questioned because patients with endoscopy-negative „heartburn” have lower response rates to acid suppression with proton pump inhibitors than do patients with endoscopy-positive „heartburn,” ie, erosive esophagitis. […] As explanation for this, 3 different mechanisms have been proposed to explain the occurrence of heartburn in the endoscopy-negative setting. They are: esophageal visceral hypersensitivity, sustained esophageal contractions, and abnormal tissue resistance. […] In this report, we review the observations in support of each concept and propose a means for reconciling them under one hypothesis: abnormal tissue resistance. […] Essential to this review and to the conclusions drawn about the pathogenesis of heartburn in nonerosive reflux disease is a reaffirmation of the definition of reflux-associated „heartburn” as an acid-mediated event requiring „relief by antacids” as a necessary component of the history.

• #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

  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.

• #1 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

  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 mechanisms underlying GERD-associated cough mainly include reflux theory and reflex theory. Historically, reflux theory proposes that the acid refluxes (gastric acid and pepsin) rising to proximal esophagus directly injure laryngopharyngeal mucosa and are microaspirated into the lower airways, which irritate the innervating cough receptors and arise cough. Reflex theory suggests that the irritants derived from reflux in distal esophagus may also trigger cough indirectly through esophageal-tracheobronchial reflex.

• #1 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

  It is generally believed that reflex theory is more important than reflux theory in the pathogenesis of GERD-associated cough since only 32-37% of patients with GERD were observed having reflux reaching the upper esophagus, and the distal esophagus is the mandatory route for all refluxes traveling up to the proximal end of esophagus as well. […] In addition, the disorder of esophageal dysmotility, which is also common in patients with GERD-associated cough, can amplify the noxious response of abnormal reflux by delaying esophageal clearance and prolonging acid exposure. […] Cough hypersensitivity underlied by airway neurogenic inflammation is responsible for the exaggerated cough reactivity to reflux, which is non-tussive in physical state but is violently tussive in patients with GERD-associated cough.

• #1 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

  Currently, how GERD-associated cough initiates remains unclear. […] The stimuli sensed and transmitted by the nerve endings innervating both esophagus and airway converge in the primary cough center and may have a neural crosstalk. […] This may produce the initiation of the cough reflex in response to the reflux-mediated irritation. […] There has been growing evidence to support that the esophageal-tracheobronchial reflex is mediated by the vagal C-fibers innervating the tracheobronchial and esophageal mucosa. […] Our study demonstrated tracheobronchial-esophageal reflex did exist and was mediated by TRPV1 signaling in the guinea pigs with repeated capsaicin inhalation. […] The tracheobronchial-esophageal reflex might provide a plausible explanation for how airway diseases, especially upper respiratory tract infection, initiated the reflux-related cough, thus producing a vicious cough-reflux loop.

• #1 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.

• #1 What is GERD and what complications can arise from it? – Canadian Digestive Health Foundation

  https://cdhf.ca/en/what-is-gerd-and-what-complications-can-arise-from-it/

  Gastroesophageal Reflux Disease, commonly known as GERD is a widely experienced disorder that is the result of a disordered valve mechanism between the esophagus (swallowing tube) and the stomach. […] With GERD, the LES fails to open and close correctly, and the stomach contents—which are acidic and contain digestive secretions—can flow back into the esophagus. This reverse flow (reflux) of food, acids and the digestive enzyme pepsin, can result in heartburn (and/or other symptoms) and potentially cause damage to the lower esophageal lining. […] People who have severe, chronic GERD (daily heartburn over many years) can develop a condition called Barrett’s Esophagus. […] Reflux of acid causes inflammation in the lower esophagus. As a result, the body tries to protect itself by changing the lining of the esophagus from its normal squamous lining (which is very sensitive to acid), to what’s called a columnar lining (which is not sensitive to acid).

• #1

  https://aesnet.org/otc/otc-medications-and-epilepsy–heartburn

  Antacids neutralize stomach acid and provide quick relief from heartburn by increasing the pH of the stomach contents. […] Antacids can impair the absorption of phenytoin. It is recommended that patients wait at least two hours after taking phenytoin before consuming antacids to ensure proper medication absorption and efficacy. […] Cimetidine inhibits histamine action at H2 receptors on gastric parietal cells, reducing stomach acid production. They may be metabolized by the same cytochromes as ASMs. […] Cimetidine can inhibit the metabolism of several ASMs, leading to elevated plasma levels and increased risk of side effects such as somnolence, ataxia, nystagmus, and cognitive disturbances. […] The inhibition is the strongest for phenytoin, which is dose dependent. […] Famotidine blocks H2 receptors but with fewer drug interactions.

• #1 Cary Gastroenterology Associates | Medications that Can Cause…

  https://www.carygastro.com/blog/medications-that-can-cause-heartburn

  W głównej mierze mechanizm powstawania zgagi polega na nieprawidłowym funkcjonowaniu dolnego zwieracza przełyku (LES), pierścienia mięśniowego, który kontroluje otwarcie między przełykiem a żołądkiem. […] Czasami dolny zwieracz przełyku nie zamyka się całkowicie lub w jakiś sposób pozwala na to, aby kwasy żołądkowe produkowane w żołądku wlewały się do przełyku. […] Jeśli lek ma potencjał do wywołania zgagi, będzie to albo poprzez bezpośrednie podrażnienie błony śluzowej przełyku, albo poprzez rozluźnienie LES. […] Nie wszystkie leki, które mogą powodować zgagę, powodują ją u wszystkich użytkowników danego leku. […] Niektóre leki stosowane w leczeniu nadciśnienia tętniczego lub chorób serca działają poprzez rozluźnienie mięśni gładkich otaczających różne naczynia krwionośne. […] Niestety, niektóre leki stosowane w leczeniu astmy mogą pogarszać objawy zgagi u niektórych pacjentów.

• #1 Chronic Heartburn | Rush

  https://www.rush.edu/news/chronic-heartburn

  Heartburn is caused by acid reflux, when acid from the stomach flows up or refluxes into the esophagus, the muscular tube that connects the throat with the stomach. The result of this acid irritating or damaging the lining of the esophagus can be a sensation of tightness, pain or discomfort in the middle of the chest what we call heartburn. […] In fact, over time, the cells of the esophagus that are repeatedly in contact with acid adjust to become more like cells found in the small intestines. This is referred to as Barrett’s esophagus. While this change in the cells can protect the esophagus from further damage caused by inflammation, people with Barrett’s esophagus may develop dysplasia, a condition that dramatically increases the risk of getting cancer of the esophagus. […] It’s important to note, however, that while these medications effectively manage symptoms, they are not a cure. The heartburn pain will go away, but the backsplash of damaging fluid still occurs.

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

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

  Although gastroesophageal reflux disease (GERD), a common chronic disease in clinical practice, has been widely studied, its potential adverse impact on patients is still a significant clinical concern. It is necessary to understand the pathogenesis of the disease and choose appropriate treatment according to its mechanism. The pathogenesis of GERD is diverse and complex. […] Our previous study suggested that the activation of nuclear factor-kappa beta (NF-B) in esophageal mucosa may be related to the injury of epithelial barrier function caused by reflux. Based on the literature and our previous study results, it is speculated that inhibition of NF-B activation may block the insult of GERD on the esophageal mucosal barrier. NF-B may play an important role in the development of GERD. This article reviews the pathogenesis of GERD and the relationship between NF-B and GERD, in order to provide new strategies for the treatment of GERD.

• #1 Got GERD? Six GERD Signs You Shouldn’t Ignore – UF Health

  https://ufhealth.org/stories/2022/got-gerd-six-gerd-signs-you-shouldnt-ignore

  Chemical irritation of the esophagus caused by acid reflux can create swelling and make it difficult for food to move through your esophagus. […] Acid reflux can lead to vocal cord irritation. […] This intervention is to recreate the normal esophageal and gastric anatomy and restore the function of the lower esophageal sphincter, allowing acid contents to stay within the stomach, Oppenheimer said.

• #1 Mechanisms of heartburn | Nature Reviews Gastroenterology & Hepatology

  https://www.nature.com/articles/ncpgasthep1160

  Heartburn is a typical symptom of GERD. The spectrum of diseases associated with GERD includes reflux esophagitis, Barrett’s esophagus and nonerosive reflux disease (NERD). […] Strong evidence exists that weakly acidic reflux and/or non-acid-related events have a significant role in the generation of heartburn. In addition to the role of nonacidic refluxate components, activation of mechanoreceptors and chemoreceptors, and a possible role for central and peripheral sensitization, has been described. […] Several mechanisms are postulated to underlie heartburn: acid reflux, weakly acidic reflux, bile reflux, mechanical stimulation of the esophagus, esophageal hyperalgesia and psychological comorbidity. […] Expanding knowledge of the pathophysiology of heartburn in patients with GERD, in particular those with NERD, will shape our understanding of heartburn, serve as a platform for further research and allow additional therapeutic options to be developed for this increasingly common clinical entity.

• #2 GERD pathogenesis, pathophysiology, and clinical manifestations | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/70/11_suppl_5/S4

  Gastroesophageal reflux disease (GERD) is a specific clinical entity defined by the occurrence of gastroesophageal reflux through the lower esophageal sphincter (LES) into the esophagus or oropharynx to cause symptoms, injury to esophageal tissue, or both. […] The pathophysiology of GERD is complex and not completely understood. An abnormal LES pressure and increased reflux during transient LES relaxations are believed to be key etiologic factors. Prolonged exposure of the esophagus to acid is another. […] Heartburn and acid regurgitation are the most common symptoms of GERD, although pathologic reflux can result in a wide variety of clinical presentations. GERD is typically chronic, and while it is generally nonprogressive, some cases are associated with development of complications of increasing severity and significance.

• #2 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.

• #2 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). […] In most persons with GERD, endogenous defense mechanisms either limit the amount of noxious material that is introduced into the esophagus or rapidly clear the material from the esophagus so that symptoms and esophageal mucosal irritation are minimized. […] When the defense mechanisms are defective or become overwhelmed so that the esophagus is bathed in acid or bile and acid-containing fluid for prolonged periods, GERD can be said to exist. (See Pathophysiology.) […] 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.

• #2 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 is defined as lower esophageal sphincter relaxation that is induced spontaneously without swallowing. […] 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.

• #2

  https://journals.lww.com/ajg/fulltext/2017/10001/pathogenesis_of_gerd__don_t_forget_the_resting_les.355.aspx

  Transient lower esophageal sphincter relaxation (TLESR) is the principal mechanism of reflux in the majority of patients with GERD. […] Our results showed a relationship between the different HRIM parameters and the IRE which we used as an indicator of the frequency of TLESRs. However, our regression model showed that only the RP can predict the frequency of IRE. […] These results support the assumption that TLESR-related reflux can happen when a relatively hypotensive LES is overcome and blown open by an abrupt increase of intra-abdominal pressure, and therapies directed on elevation of LES RP may have an impact on decreasing the frequency of TLESRs and justifying their trial in PPI-refractory GERD patients.

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

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

  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. […] 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 inflammation of the mucosa and esophageal wall is associated with decreased LES pressure and esophageal motility that can impact on the acid burden to the mucosa through increased reflux and delayed esophageal clearance.

• #2 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. […] 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. […] When mucosal damage occurs (esophagitis), a vicious cycle can ensue to accentuate and maintain the GERD.

• #2 Got GERD? Six GERD Signs You Shouldn’t Ignore – UF Health

  https://ufhealth.org/stories/2022/got-gerd-six-gerd-signs-you-shouldnt-ignore

  GERD is a condition in which acid from the stomach persistently regresses back up into the esophagus. […] This phenomenon takes place because a valve at the end of the esophagus, called the lower esophageal sphincter, fails to close properly when food goes in the stomach during a meal, Oppenheimer said. […] A hiatal hernia develops when a portion of the stomach migrates up the chest due to enlargement of the diaphragmatic hiatus, Oppenheimer said. The presence of a hiatal hernia can interfere with the lower esophageal sphincter function. […] A painful burning sensation in the middle of your chest caused by secondary irritation of the esophageal lining by the regurgitated stomach acid contents. […] Regurgitation of food or acid back into the mouth can be an indicator of GERD, especially when bending over or lying recumbent. This is most commonly secondary to faulty lower esophageal sphincter function.

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

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

  It is extremely important to identify which of these components is defective so that an effective therapy can be applied. […] Proper esophageal clearance is an extremely important factor in preventing mucosal injury. Esophageal clearance must be able to neutralize the acid refluxed through the lower esophageal sphincter. […] Abnormal peristalsis can cause inefficient and delayed acid clearance. […] The lower esophageal sphincter (LES) is defined by manometry as a zone of elevated intraluminal pressure at the esophagogastric junction. […] LES dysfunction occurs via one of several mechanisms: transient relaxation of the LES (most common mechanism), permanent LES relaxation, and transient increase of intra-abdominal pressure that overcomes the LES pressure. […] 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.

• #2 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.

• #2 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.

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

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

  Evidence is accumulating that inflammation affects nerves and muscle to alter LES and esophageal body motility. […] Both a decrease in cholinergic excitatory and an increase in nitrergic and other inhibitory mechanisms appear to be involved. […] 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.

• #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

  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).

• #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). […] 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 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 NF-κB: A novel therapeutic pathway for gastroesophageal reflux disease?

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

  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. […] NF-B can directly regulate tight junction protein expression and impair epithelial barrier function by relaxing tight junctions. […] 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.

• #2 New mechanism of acid reflux damage discovered by researchers | Designs for Health

  https://www.casi.org/si-42214/new-mechanism-of-acid-reflux-damage-discovered-by-researchers

  According to a new study published three days ago in The Journal of the American Medical Association researchers found the damage of the esophagus in gastroesophageal reflux disease (GERD) to be cytokine-mediated due to inflammation and not caused directly by the acid in the stomach. […] Now according to researchers at UT Southwestern Medical Center and the Dallas VA Medical Center this damage to the esophageal lining is occurring through an inflammatory response by cytokines. […] This research builds on previous work in mice which demonstrated that it takes several weeks from the time stomach acid is introduced into the esophagus before damage occurs. If the damage is from HCl it should develop immediately. […] This new information will probably not change the traditional approach to treating GERD in the immediate future but we may eventually see a shift to targeting the cytokines and inflammation which is really causing the damage to the esophagus.

• #2 Functional heartburn: An underrecognized cause of PPI-refractory symptoms | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/86/12/799

  Functional heartburn is defined as retrosternal burning in the absence of objective evidence of GERD, mucosal abnormality (ie, erosive esophagitis), or major motility disorder. The symptoms are theorized to result from hypersensitivity of the visceral nerves of the esophagus, which may be exacerbated by central sensitization, hypervigilance, stress, and anxiety. The pathogenesis is poorly understood, but it may involve activation of inflammatory mediators in the esophagus, alterations in esophageal mucosal integrity, increased chemical and pressure sensation in the esophagus, and both peripheral and central sensitization. […] Functional heartburn is the most common cause of failure of proton pump inhibitor (PPI) therapy, but it is often overlooked by internists and gastroenterologists. […] The most common cause of this PPI-refractory heartburn is functional heartburn, a functional or hypersensitivity disorder of the esophagus.

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

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

  Acid reflux happens when the sphincter muscle at the lower end of the esophagus relaxes at the wrong time, allowing stomach acid to back up into the esophagus. This can cause heartburn and other symptoms. Frequent or constant reflux can lead to GERD. […] Gastroesophageal reflux disease happens when stomach acid flows back up into the esophagus and causes heartburn. It’s often called GERD for short. This backwash is known as acid reflux, and it can irritate the lining of the esophagus. […] GERD is caused by frequent acid reflux or reflux of nonacidic content from the stomach. […] If the sphincter does not relax as is typical or it weakens, stomach acid can flow back into the esophagus. This constant backwash of acid irritates the lining of the esophagus, often causing it to become inflamed.

• #2 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

  Tracheobronchial-esophageal reflex might initiate reflux-induced cough provoked by the upper respiratory tract infection through a central crosstalk between the neural pathways linking the airway and esophagus in a manner similar but opposite to esophageal-tracheobronchial reflex. […] Esophageal reflux monitoring provides the main diagnostic criteria for GERD-associated cough. […] AET and SAP have demonstrated significant diagnostic efficiency as reflux diagnostic parameters, but they are not yet perfect and far from being the gold standard. […] It is necessary to optimize the current standards and explore new criteria with higher diagnostic potency.

• #2 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.

• #2 What is GERD and what complications can arise from it? – Canadian Digestive Health Foundation

  https://cdhf.ca/en/what-is-gerd-and-what-complications-can-arise-from-it/

  Gastroesophageal Reflux Disease, commonly known as GERD is a widely experienced disorder that is the result of a disordered valve mechanism between the esophagus (swallowing tube) and the stomach. […] With GERD, the LES fails to open and close correctly, and the stomach contents—which are acidic and contain digestive secretions—can flow back into the esophagus. This reverse flow (reflux) of food, acids and the digestive enzyme pepsin, can result in heartburn (and/or other symptoms) and potentially cause damage to the lower esophageal lining. […] People who have severe, chronic GERD (daily heartburn over many years) can develop a condition called Barrett’s Esophagus. […] Reflux of acid causes inflammation in the lower esophagus. As a result, the body tries to protect itself by changing the lining of the esophagus from its normal squamous lining (which is very sensitive to acid), to what’s called a columnar lining (which is not sensitive to acid).

• #2 What is GERD and what complications can arise from it? – Canadian Digestive Health Foundation

  https://cdhf.ca/en/what-is-gerd-and-what-complications-can-arise-from-it/

  This protective action presents a problem because if you have normal squamous lining you will feel the acid, and therefore you will experience heartburn symptoms, but as the lining of the esophagus changes you are no longer sensitive to the acid. […] Further to this, there is evidence that a small proportion of those living with Barrett’s esophagus are at an increased risk of developing esophageal cancer.

• #2 How Does PEPCID® Work? | Famotidine Mechanism of Action | PEPCID® Professional

  https://kenvuepro.com/en-us/pepcid/how-does-pepcid-work

  PEPCID binds to histamine H2 receptors on the parietal cell surface, blocking histamine from stimulating those receptors. PEPCID also suppresses histamine-induced secretion of basal gastric acid. […] This MOA means PEPCID AC and Maximum Strength PEPCID AC reduce acid production effectively, whether taken before, during, or after mealswhenever patients anticipate or experience symptoms. […] PEPCID works fast to relieve heartburn and provides lasting relief. PEPCID is not indicated for the treatment of gastroesophageal reflux disease (GERD). […] A clinical trial showed that even 4 hours after taking PEPCID AC, patients who ate a symptom-inducing meal experienced significantly reduced heartburn, and symptom protection continued for another 4 hours.

• #2

  https://aesnet.org/otc/otc-medications-and-epilepsy–heartburn

  Famotidine is generally considered a safer alternative than cimetidine as it has a lower potential for drug interactions. […] Omeprazole irreversibly inhibits the H+/K+ ATPase enzyme system of gastric parietal cells, effectively reducing stomach acid production. […] Omeprazole can increase the plasma concentrations of phenytoin, clobazam, and diazepam by inhibiting the activity of CYP2C19 as well as carbamazepine through an unknown mechanism. Elevated levels of these ASMs can enhance the risk of dose-related side effects such as dizziness, nausea, and toxicity. […] Antacids should be taken at least two hours after taking ASMs to prevent absorption interference. […] Famotidine is generally considered a safer option than cimetidine to avoid increasing the plasma levels of ASMs and phenytoin specifically. […] Omeprazole and esomeprazole may slow the metabolism of certain antiseizure medicines, like phenytoin, carbamazepine, clobazam, and diazepam.

• #2 Cary Gastroenterology Associates | Medications that Can Cause…

  https://www.carygastro.com/blog/medications-that-can-cause-heartburn

  Leki przeciwlękowe i trójcykliczne leki przeciwdepresyjne mogą podobnie mieć działanie rozluźniające na dolny zwieracz przełyku, a także podrażniać błonę śluzową żołądka. […] Podrażnienie w obu sytuacjach może powodować zgagę lub inne objawy związane z GERD. […] Bisfosfoniany to rodzaj leku, który może bezpośrednio podrażniać błonę śluzową przełyku. […] Irytacja w obu sytuacjach może powodować zgagę lub inne objawy związane z GERD.

• #2 Chronic Heartburn | Rush

  https://www.rush.edu/news/chronic-heartburn

  That’s because proton pump inhibitors can’t fix the underlying mechanical problem the dysfunction of the valve between the esophagus and stomach. Long-term use of proton pump inhibitors can also cause significant side effects, and you must consider the lifetime cost of taking these medications. […] For these reasons, surgery may be necessary to correct the valve mechanism, with the goal of eliminating the need for reflux medication. Advances in technology have improved doctors ability to tailor procedures to each individual patient, with greatly improved outcomes. […] Common procedures for GERD include laparoscopic Nissen fundoplication, transoral incisionless fundoplication (also called TIF Esophix) and magnetic sphincter augmentation (also called LINX).

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

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

  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. […] 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.

• #2 Gastroesophageal Reflux | Columbia Surgery

  https://columbiasurgery.org/conditions-and-treatments/gastroesophageal-reflux

  Gastroesophageal reflux disease (GERD), also called acid reflux, is a common digestive disorder in which stomach contents regurgitate (reflux) into the esophagus. Also called heartburn, GERD often causes inflammation and damage to the esophagus and occasionally to the lungs and vocal cords. Prolonged untreated GERD can lead to Barretts esophagus, a dangerous precancerous condition. […] GERD has a variety of causes. Abnormality or weakness in the LES (lower esophageal sphincter a muscle at the junction of the esophagus and stomach), usually associated with hiatal hernia, contributes to the failure of the body’s natural anti-reflux mechanism. […] While GERD can have several causes, surgery is most effective for those patients whose GERD is caused by a defective lower esophageal sphincter (LES), the muscle connecting the esophagus with the stomach. […] The goal of the procedure is to restore the physiologic equivalent of the LES by wrapping the stomach around the lower esophagus. […] As the stomach becomes distended during a meal, the wrap compresses the lower esophagus, preventing reflux, thus imitating the action of a valve.

• #2 The pathogenesis of heartburn in nonerosive reflux disease: a unifying hypothesis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/15765412/

  Heartburn is a symptom complex that has traditionally been accepted as an acid-mediated event and a reliable indicator of gastroesophageal reflux disease. […] Recently, however, these concepts have been questioned because patients with endoscopy-negative „heartburn” have lower response rates to acid suppression with proton pump inhibitors than do patients with endoscopy-positive „heartburn,” ie, erosive esophagitis. […] As explanation for this, 3 different mechanisms have been proposed to explain the occurrence of heartburn in the endoscopy-negative setting. They are: esophageal visceral hypersensitivity, sustained esophageal contractions, and abnormal tissue resistance. […] In this report, we review the observations in support of each concept and propose a means for reconciling them under one hypothesis: abnormal tissue resistance. […] Essential to this review and to the conclusions drawn about the pathogenesis of heartburn in nonerosive reflux disease is a reaffirmation of the definition of reflux-associated „heartburn” as an acid-mediated event requiring „relief by antacids” as a necessary component of the history.

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