Refers to the retrograde movement of gastric fluid into the esophagus and is not a state of excess gastric acidity, which is the target of most GERD therapies.
A condition in which the reflux of stomach contents causes symptoms and complications.
7-20% of Americans experience reflex symptoms daily and 15-44% experience symptoms once per month.
GERD is common, accounting for more than 5.6 million physician visits each year.
From 10% to 20% of adults in Western countries and nearly 5% of those in Asia experience GERD symptoms at least weekly.
The prevalence of GERD symptoms is increasing by about 4% per year, in parallel with increases in obesity rates and reduction in prevalence of Helicobacter pylori over the past several decades.
Symptoms of GERD are less frequent in the elderly, but the severity of disease is greater than that in younger patients.
The prevalence of GERD is high and increasing, with greater rates in high income countries of 15-25%, than in most low and middle income countries less than 10%.
Costs related to GERD in the US is estimated $10 billion annually.
The predominant mechanism of gastroesophageal reflux is thought to be transient relaxation of the lower esophageal sphincter but impaired esophageal clearance, anatomical disruption of the lower esophageal sphincter complex, and delayed gastric emptying may be other mechanisms.
The phenotypic presentation of GERD includes: nonerosive reflux disease in 60 to 70% of patients, erosive esophagitis in 30%, and Barrett’s esophagus in 5 to 12%.
Non-erosive reflux disease is associated with abnormal exposure to esophageal acid in the absence of findings of mucosal breaks on endoscopy, and erosive esophagitis is characterized by breaks in the esophageal mucosa.
Some experience extraesophageal symptoms of GERD: asthma, laryngitis, pharyngitis, chronic cough, sinusitis, idiopathic pulmonary fibrosis, dental erosions, and recurrent otitis media.
Patients may not have symptoms of GERD even if they have objective evidence of it such as erosive esophagitis or Barrett esophagus.
Established risk factors for developing GERD: increase body mass, tobacco smoking, and genetic predisposition, older age, current smoking, use of nonsteroidal anti-inflammatory drugs, low socioeconomic status, and female gender.
Historically, patients have been advised to avoid smoking, chocolate, carbonated beverages, spicy food, fatty food, alcohol, and large meals.
But, no study has found improvement in GERD symptoms with cessation of either smoking or alcohol.
No food has been conclusively linked with increased GERD symptoms: no consistent associations have been established between GERD symptoms and fatty food, spicy food, coffee, carbonated beverages, chocolate, citrus, or mint.
Factors now known to contribute to GERD include:
Transient lower esophageal sphincter (LES) relaxation.
Sliding hiatal hernia
Low LES pressure
Acid pocket development due to poor mixing of acid with chyme in the proximal stomach
Increased gastroesophageal junction distensibility
Obesity
Delayed gastric emptying.
Most symptoms are caused by acid reflux.
Acid reflux extend high into the esophagus is associated with worse symptoms, regardless of the acidity of the bolus.
GERD patients may have an increased perception of esophageal sensation with a lower sensory threshold for reflux.
Reflux hypersensitivity refers to an heightened response to nonpathologic reflux.
Functional heartburn refers to the presence of symptoms without any evidence of abnormal exposure: benign conditions.
When the stomach contracts, it closes off the esophagus instead of squeezing stomach acids into it.
This prevents the reflux of gastric acid.
Esophageal pH monitoring is indicated in patients with persistent symptoms and normal findings on endoscopy.
Barium esophagography is not indicated and has poor sensitivity and specificity for GERD.
It is possible that sustained longitudinal muscle esophageal contractions can lead to transient ischemia of the esophageal wall that results in GERD symptoms.
Defined by its cardinal symptoms of recurrent in troublesome heartburn and regurgitation.
GERD is present in 18-28% of patients.
GERD complications include: stricture, Barrett’s esophagus, and esophageal adenocarcinoma.
Recumbency can worsen GERD symptoms, especially after meals.
Due to transit relaxations of the lower esophageal sphincter with the severity of the disease attributable to the degree and duration of acid exposure in the esophagus.
In evaluating GERD patients should be queried about the frequency, severity, and duration of symptoms, specific triggers of dietary or non-dietary nature, timing of symptoms such as daytime, nighttime, or both, and the presence of associated symptoms such as dysphasia, odynophagia, weight loss, anorexia, vomiting, and upper G.I. bleeding.
Rome IV classification: erosive esophagitis, functional dyspepsia, nonerosive reflux disease, and asymptomatic GERD.
Annual cost for management exceeds $12 billion.
The pressure gradient between the stomach and esophagus is the competency of the EGJunction and lower esophageal sphincter, and what define whether gastric fluid will abnormally enter into the esophagus, including during physiologic transient lower esophageal sphincter relaxations.
5-10% have Barrett’s esophagus.
An estimated 3% to 6% of individuals with gastric reflux have Barrett’s esophagus, the precursor lesion to esophageal adenocarcinoma, but only about 20% of these are diagnosed.
The esophageal cancer incidence among patients without Barrett esophagus is only 0.07% per year.
Compared to a control group without symptoms there is an 8 fold increase in the risk of esophageal adenocarcinoma for patients with heartburn and or regurgitation weekly, an 11 fold increased in those with nocturnal symptoms of GERD and a more than 43 fold increase in patients with more than 20 years of GERD symptoms.
Nocturnal reflux is associated with complications such as esophageal erosions, ulcerations, respiratory symptoms and increased risk of esophageal adenocarcinoma.
Patients with symptoms of reflux at night are associated with a risk of developing esophageal adenocarcinoma nearly 11 times higher than those without nighttime symptoms.
Most patients with GERD induced chest pain do not have esophagitis.
Approximately 78% of patients with chronic hoarseness and more than 80% of patients with asthma have symptoms that may be associated with GERD.
Associated with cough, dyspnea and wheezing.
May precipitate asthma.
Postulated to cause bronchoconstriction by microaspiration into the airways directly, and indirectly via vagal mediated effects of acid on the upper airway or esophagus.
Asthma may lead to the development of GERD by changing the pressure gradient between the thorax and the abdomen causing displacement of the lower esophageal sphincter into the chest, by induction of pulmonary hyperinflation exacerbating diaphragmatic dysfunction, and by lowered esophageal sphincter tone decreased by use of bronchodilators.
Esophageal pH monitoring is the gold standard for evaluating esophageal acid exposure and GERD.
It is mainly a clinical diagnosis based on typical symptoms of heartburn and acid regurgitation, and often does not require endoscopic confirmation.
24-h impedance combined with pH-metry is currently considered as the gold standard for diagnosis of gastroesophageal reflux disease.
All patients with GERD may not require these investigations, but those with atypical symptoms, those refractory to medical treatment and requiring surgery do.
pH monitoring has a sensitivity and specificity of 70-96% in the diagnosis of GERD.
Refluxed material is a combination of gastric acids and duodenal bile.
Endoscopy is the gold standard for assessing complications of GERD.
Endoscopy is warranted: in patients dysphagia, anemia, weight loss, bleeding, and recurrent vomiting.
Weight loss can help reduce and eliminate GERD symptoms.
Endoscopy is generally limited to patients with GERD who report alarm symptoms, who have no response or an incomplete response to treatment or have recurrent GERD after successful eight week course of empirical therapy, who are candidates for anti-reflux for bariatric surgery, or who were increased risk for Barrett’s esophagus.
Endoscopy has a low sensitivity for GERD because most patients have a normal appearing esophagus on upper endoscopy.
81% of obese patients who completed a structured weight loss program had a reduction in GERD symptoms, and 65% had complete resolution of symptoms.
In a retrospective study, with more than 15,000 patients, there was an association between improvement in GERD symptoms and reduction in body mass index (BMI) in obese patients who lost at least 2 kg/m2 in BMI
Dysphagia can be a symptom of uncomplicated GERD, but its presence warrants more intensive examination for strictures, rings, malignancy, or esophageal dysmotility.
Endoscopy is performed in any patient with the alarming symptoms, and also in patients whose symptoms do not respond to a PPI.
Abnormal endoscopic findings in GERD: erosive esophagitis, strictures, and Barrett esophagus.
Many patients with GERD have normal findings on endoscopy.
Biopsy samples from the esophagus should be obtained to rule out eosinophilic esophagitis.
Endoscopic views of esophagitis grades. (A) Grade A-1 or more mucosal breaks no longer than 5 mm that do not extend between the tops of two mucosal folds.
(B) Grade B-1 or more mucosal breaks longer than 5 mm that do not extend between the tops of two mucosal folds.
(C) Grade C-1 or more mucosal breaks that are continuous between the tops of 2 or more mucosal folds, but involve less than 75% of the circumference.
(D) Grade D-1 or more mucosal breaks that involve at least 75% of the esophageal circumference.
Commonly associated with asthma.
Studies promote elevating the head of the bed, sleeping in the left decubitus position, and, in those with nocturnal GERD symptoms, avoiding meals in the 2 to 3 hours before bedtime.
A sleep positional therapy device places the user in the left decubitus position at an incline and has been an effective tool for those with nocturnal symptoms.
Proton pump inhibitors agents of choice for moderate to severe erosive esophagitis and are more effective at preventing recurrence than histamine2-receptor antagonists.
In a randomized trial, remission of erosive esophagitis was found in 80.2% of those taking omeprazole 20 mg daily vs 39.4% in those taking ranitidine 150 mg daily.
Management of patients with GERD symptoms are given a trial of PPI treatment.
If lifestyle interventions fail, drug treatment options are PPIs, histamine 2 receptor antagonists (H2RAs), and antacids.
Antacids are effective for reducing postprandial esophageal acid exposure.
PPIs are the therapy of choice for symptomatic relief and healing of erosive esophagitis.
Compared with H2RAs, PPIs have been shown to provide improved healing rates and fewer relapses in patients with erosive esophagitis.
No study has shown a major difference in symptom control between the multiple PPIs.
A short course proton pump inhibitors therapy has a 78% sensitivity and 54% specificity in accurately diagnosing GERD.
Up to 40% of patients with GERD find partial or no symptom relief with first-line therapies with PPIs.
An 8-week course of therapy is needed to allow for healing.
In non-responding patients esophageal impedance and pH testing are performed to determine if there is persistent acidic or nonacidic reflux.
Reflux testing allows the assessment of the degree, height, and type of gastroesophageal reflux, and the correlation between symptoms and reflux events.
Ambulatory 24 hour pH managing is highly sensitive and specific in patients with erosive esophagitis.
With reflux testing, a pH catheter is introduced into the nose and placed above the proximal margin of the lower esophageal sphincter and the 24 hour esophageal impedance pH monitor detects changes in response to liquid reflux or belched air.
This technique has a sensitivity of approximately 90%.
A wireless pH capsule can provide similar information: it is attached to the distal esophagus, and a pH monitor records changes and transmit it to a recording device.
A short course of PPI therapy has a 78% sensitivity and 54% specificity in accurately diagnosing GERD: If typical symptoms resolve with a trial of a PPI, GERD should be diagnosed and the patient should continue taking a PPI daily.
PPIs inactivate the hydrogen potassium ATPase molecules of the parietal cell, and inhibit gastric acid secretion.
Parietal cell are maximally stimulated after a meal, and PPIs activated at that time have optimal acid suppression.
All PPIs should be taken 30 to 60 minutes before a meal for optimal pH control except for dexlansoprazole.
Dexlansoprazole employs dual delayed-release technology leading to sustained plasma drug concentrations, and can therefore be taken at any time of day.
For patients with daytime symptoms, a PPI should be taken once daily in the morning for daytime symptoms.
For nighttime symptoms, the dose should be taken in the evening.
After the initial 8-week course of therapy, most patients with GERD should attempt to take the lowest dose required to manage their symptoms.
Some patients may require long term PPI treatment.
A controlled trial found no association of PPIs with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections.
Patients with reflux esophagitis will have endoscopic and symptomatic relapse up to 80% of the time if therapy is discontinued or drug dosage is decreased.
The underlying mechanisms that lead to reflux of stomach contents into the esophagus and subsequent symptoms or esophagitis range from increased transient relaxations of the esophageal sphincter, promotion of increased acid with bile reflux, derangements of esophageal sphincter, with or without esophageal hypersensitivity plus psychological distress.
It is possible disordered gastric accommodation increases esophageal sphincter relaxation, which may occur in functional dyspepsia or alterations in the microbiome and bacterial fermentation in the intestine.
Current approach of choice for surgical treatment is a minimally invasive transabdominal antireflux procedure.
Contemporary antireflux therapy for chronic GERD, with either acid suppression by esomeprazole or by laparoscopic antireflux surgery, most patients achieve and remain in remission at 5 years (Galmiche JP et al).
Esomeprazole was shown, in a meta-analysis comparing it with other PPIs, to increase the probability of healing erosive esophagitis at 4 and 8 weeks.
Long-Term Usage of Esomeprazole vs Surgery for Treatment of Chronic GERD (LOTUS) trial at 5 years found remission rates at 5 years were higher in the esomeprazole group 92% than laparoscopic antireflux surgery 85%, with more regurgitation with esomeprazole, and more dysphagia, bloating and flatulence.
Although antacids and PPI drug therapy can reduce the effects of reflux acid, successful surgical treatment has the advantage of eliminating drug side-effects and damaging effects from other components of reflux such as bile or gastric contents.
Patients have decreased quality of life, decreased productivity and impaired well-being.
Only 2-3% of acid reflux events are perceived by patients with GERD.
Elderly patients with acid reflux in the United States are 3.47, 3.23, 2.88, and 2.37 times as likely as those without acid reflux to be diagnosed with laryngeal, hypopharyngeal, oropharyngeal, and tonsillar cancers, respectively (MCcoul ED).
Treatment:
Treatment of GERD includes lifestyle, modifications, alone, or in combination with pharmacologic, endoscopic, or surgical interventions, depending on how severe the disease is.
Modification evidence is strongest for weight loss, elevation of the head of the bed, and avoidance of food for at least three hours before bedtime.
In a prospective study of women who adhered to anti-reflux lifestyle approaches of maintaining a normal weight, not smoking, engaging in moderate physical activity, avoiding more than 2 cups of coffee, tea or soda and eating a prudent diet had only half the risk of GERD symptoms compared to women who did not adhere to such lifestyle changes.
In patients with typical symptoms of GERD, without atypical features or without complications, a trial of acid suppression therapy should be tried for 4-8 weeks.
Initial treatment includes antacids, histamine H2 receptor antagonists twice daily or a proton pump inhibitor before the first meal of the day.
Antacids have an immediate effect, but only of very short term.
Histamine 2 receptor antagonists are mainly used to treat breakthrough nocturnal symptoms.
Histamine 2 receptor antagonists are used on demand for treatment of heartburn or daily for mild to moderate GERD symptoms or low-grade erosive esophagitis and in patients who have not had a response to PPI therapy.
Daily use of histamine 2 receptor antagonists may result in tachyphylaxis.
Guidelines indicate that patients with typical symptoms should first try a proton pump inhibitor (PPI).
If reflux symptoms persist after 8 weeks on a PPI, endoscopy of the esophagus is recommended, with biopsies taken to rule out eosinophilic esophagitis.
In patients refractory to PPIs and have persistent heartburn symptoms other options include reflux reducing medications such as baclofen or neuromodulators such as tricyclic antidepressants that dampen visceral hypersensitivity.
Baclofen and neuromodulators have unacceptable side effects and their efficacy is low and of short duration.
Endoscopic techniques are alternative approaches to the management of GERD and augment the anti-reflex barrier, such techniques include the esophageal radiofrequency energy delivery, increasing the thickness of the esophagogastric junction musculature and transoral incisionless fundoplication which forms of partial wrap around the lower esophagus.
Nissen fundoplication,is the most widely performed antireflux surgery.
It involves reducing the hiatal hernia and wrapping the gastric fundus partially or completely around the lower esophagus to restore the LES barrier.
Indications for Nissen fundoplication procedure: are presence of a large hiatal hernia, reflux esophagitis or GERD symptoms refractory to medical therapy, or adverse effects of medical therapy.
A trial comparing laparoscopic fundoplication with esomeprazole therapy found similar remission rates after 3 years and a higher rate with esomeprazole after 5 years.
Prior to fundoplication esophageal manometry should be obtained before surgery to screen for esophageal aperistalsis, as this is an absolute contraindication to the procedure.
Manometry will exclude other motility disorders as well.
Antireflux surgery is not recommended in PPI nonresponders.
A magnetic sphincter augmentation procedure (Linx) is a minimally invasive alternative to fundoplication.
It involves laparoscopic insertion of a band of magnetic beads around the LES, which allows passage of food and then closes to prevent acid reflux.
Antireflux surgery is not recommended in PPI nonresponders.
Antireflux surgery can have severe side effects: dysphagia, gas bloat syndrome, and flatulence and the intended effect may only be temporary, as up to 60% of patients will require antireflux medications regularly in the decade afterward.
Patients who undergo such surgery have better short-term quality of life, but no significant improvements in short-term or long-term symptom control as compared with medication treated patients.
Complications of surgery include gas-bloat syndrome with the inability to properly vent the stomach, resulting in a bloating sensation, dysphasia, diarrhea, and relapse of heartburn.
Roux-en-Y gastric bypass is a surgical option for morbidly obese patients: A prospective study with 53 patients showed an improvement in GERD symptoms, reflux esophagitis, and esophageal acid exposure for more than 3 years following bypass.
Other endoscopic treatments for GERD include:
Transoral incisionless fundoplication using the Esophyx device.
Radiofrequency energy delivery to the LES.
Endoscopic anterior fundoplication using the Medigus ultrasonic surgical endostapler
Anti-reflux surgery, fundoplication, which creates a barrier to reflux of gastric material should relieve PPI refractory heartburn that is reflux related.
In practice, however, patients unresponsive to PPIs are often not responsive to surgery either.