Gastroesophageal Reflux

Gastroesophageal Reflux



Definition of Gastroesophageal Reflux

Gastroesophageal reflux disease (GERD), gastro-oesophageal reflux disease (GORD), gastric reflux disease, or acid reflux disease is a chronic symptom of mucosal damage caused by stomach acid coming up from the stomach into the esophagus.

GERD is usually caused by changes in the barrier between the stomach and the esophagus, including abnormal relaxation of the lower esophageal sphincter, which normally holds the top of the stomach closed, impaired expulsion of gastric reflux from the esophagus, or a hiatal hernia. These changes may be permanent or temporary.

Treatment is typically via lifestyle changes and medications such as proton pump inhibitors, H2 receptor blockers or antacids with or without alginic acid. Surgery may be an option in those who do not improve. In the Western world between 10 and 20% of the population is affected.

Cause of Gastroesophageal Reflux

GERD is caused by a failure of the cardia. In healthy patients, the “Angle of His”—the angle at which the esophagus enters the stomach—creates a valve that prevents duodenal bile, enzymes, and stomach acid from traveling back into the esophagus where they can cause burning and inflammation of sensitive esophageal tissue.

Factors that can contribute to GERD:

  • Hiatal hernia, which increases the likelihood of GERD due to mechanical and motility factors.
  • Obesity: increasing body mass index is associated with more severe GERD. In a large series of 2000 patients with symptomatic reflux disease, it has been shown that 13% of changes in esophageal acid exposure is attributable to changes in body mass index.
  • Zollinger-Ellison syndrome, which can be present with increased gastric acidity due to gastrin production.
  • Hypercalcemia, which can increase gastrin production, leading to increased acidity.
  • Scleroderma and systemic sclerosis, which can feature esophageal dysmotility.
  • The use of medicines such as prednisolone.
  • Visceroptosis or Glénard syndrome, in which the stomach has sunk in the abdomen upsetting the motility and acid secretion of the stomach.

GERD has been linked to a variety of respiratory and laryngeal complaints such as laryngitis, chronic cough, pulmonary fibrosis, earache, and asthma, even when not clinically apparent. These atypical manifestations of GERD is commonly referred to as laryngopharyngeal reflux or as extraesophageal reflux disease (EERD).

Factors that have been linked with GERD, but not conclusively:

  • Obstructive sleep apnea
  • Gallstones, which can impede the flow of bile into the Duodenum, which can affect the ability to neutralize gastric acid

In 1999, a review of existing studies found that, on average, 40% of GERD patients also had H. pylori infection. The eradication of H. pylori can lead to an increase in acid secretion, leading to the question of whether H. pylori-infected GERD patients are any different than non-infected GERD patients. A double-blind study, reported in 2004, found no clinically significant difference between these two types of patients with regard to the subjective or objective measures of disease severity.

Signs and symptoms of Gastroesophageal Reflux

Adults

The most-common symptoms of GERD are:

  • Heartburn
  • Regurgitation
  • Trouble swallowing (dysphagia)

Less-common symptoms include:

  • Pain with swallowing/sore throat (odynophagia)
  • Increased salivation (also known as water brash)
  • Nausea
  • Chest pain

GERD sometimes causes injury of the esophagus. These injuries may include:

  • Reflux esophagitis – necrosis of esophageal epithelium causing ulcers near the junction of the stomach and esophagus
  • Esophageal strictures – the persistent narrowing of the esophagus caused by reflux-induced inflammation
  • Barrett’s esophagus – intestinal metaplasia (changes of the epithelial cells from squamous to intestinal columnar epithelium) of the distal esophagus
  • Esophageal adenocarcinoma – a rare form of cancer

Several other atypical symptoms are associated with GERD, but there is good evidence for causation only when they are accompanied by esophageal injury. These symptoms are:

  • Chronic cough
  • Laryngitis (hoarseness, throat clearing)
  • Asthma
  • Erosion of dental enamel
  • Dentine hypersensitivity
  • Sinusitis and damaged teeth
  • Pharyngitis
  • Globus pharingeus and globus hystericus (condition of feeling of choking, foreign object in throat)

Some people have proposed that symptoms such as sinusitis, recurrent ear infections, and idiopathic pulmonary fibrosis are due to GERD; however, a causative role has not been established.

Children

GERD may be difficult to detect in infants and children, since they cannot describe what they are feeling and indicators must be observed. Symptoms may vary from typical adult symptoms. GERD in children may cause repeated vomiting, effortless spitting up,coughing, and other respiratory problems, such as wheezing. Inconsolable crying, refusing food, crying for food and then pulling off the bottle or breast only to cry for it again, failure to gain adequate weight, bad breath, and belching or burping are also common. Children may have one symptom or many; no single symptom is universal in all children with GERD.

Of the estimated 4 million babies born in the US each year, up to 35% of them may have difficulties with reflux in the first few months of their lives, known as ‘spitting up’. One theory for this is the “fourth trimester theory” which notes most animals are born with significant mobility, but humans are relatively helpless at birth, and suggests there may have once been a fourth trimester, but children began to be born earlier, evolutionarily, to accommodate the development of larger heads and brains and allow them to pass through the birth canal  and this leaves them with partially undeveloped digestive systems.

Most children will outgrow their reflux by their first birthday. However, a small but significant number of them will not outgrow the condition. This is particularly true when a family history of GERD present.

Barrett’s esophagus

GERD may lead to Barrett’s esophagus, a type of intestinal metaplasia, which is in turn a precursor condition for carcinoma. The risk of progression from Barrett’s to dysplasia is uncertain, but is estimated at about 20% of cases. Due to the risk of chronic heartburn progressing to Barrett’s, EGD every five years is recommended for patients with chronic heartburn, or who take drugs for chronic GERD.

Risk factors for Gastroesophageal Reflux

Conditions that can increase your risk of GERD include:

  • Obesity
  • Pregnancy
  • Smoking
  • Dry mouth
  • Asthma
  • Diabetes
  • Delayed stomach emptying
  • Connective tissue disorders, such as scleroderma
  • Hiatal hernia
  • Hypercalcemia
  • Zollinger-Ellison syndrome
  • Visceroptosis or Glénard syndrome
  • Diagnosis of Gastroesophageal Reflux

Diagnosis of Gastroesophageal Reflux

The diagnosis of GERD is usually made when typical symptoms are present. Reflux can be present in people without symptoms and the diagnosis requires both symptoms or complications and reflux of stomach content.

Other investigations may include esophagogastroduodenoscopy (EGD). Barium swallow X-rays should not be used for diagnosis. Esophageal manometry is not recommended for use in diagnosis being recommended only prior to surgery. Ambulatory esophageal pH monitoring may be useful in those who do not improve after PPIs and is not needed in those in whom Barrett’s esophagus is seen. Investigations for H. pylori is not usually needed.

The current gold standard for diagnosis of GERD is esophageal pH monitoring. It is the most objective test to diagnose the reflux disease and allows monitoring GERD patients in their response to medical or surgical treatment. One practice for diagnosis of GERD is a short-term treatment with proton-pump inhibitors, with improvement in symptoms suggesting a positive diagnosis. Short-term treatment with proton-pump inhibitors may help predict abnormal 24-hr pH monitoring results among patients with symptoms suggestive of GERD.

Endoscopy

Endoscopy, the looking down at the stomach with a fiber-optic scope, is not routinely needed if the case is typical and responds to treatment. It is recommended when people either do not respond well to treatment or have alarm symptoms, including dysphagia, anemia, blood in the stool (detected chemically), wheezing, weight loss, or voice changes. Some physicians advocate either once-in-a-lifetime or 5- to 10-yearly endoscopy for patients with longstanding GERD, to evaluate the possible presence of dysplasia or Barrett’s esophagus.

Biopsies performed during gastroscopy may show:

  • Edema and basal hyperplasia (nonspecific inflammatory changes)
  • Lymphocytic inflammation (nonspecific)
  • Neutrophilic inflammation (usually due to reflux or Helicobacter gastritis)
  • Eosinophilic inflammation (usually due to reflux): The presence of intraepithelial eosinophils may suggest a diagnosis of eosinophilic esophagitis (EE) if eosinophils are present in high enough numbers. Less than 20 eosinophils per high-power microscopic field in the distal esophagus, in the presence of other histologic features of GERD, is more consistent with GERD than EE.
  • Goblet cell intestinal metaplasia or Barrett’s esophagus
  • Elongation of the papillae
  • Thinning of the squamous cell layer
  • Dysplasia
  • Carcinoma

Reflux changes may not be erosive in nature, leading to “nonerosive reflux disease”.

Differential diagnosis

Other causes of chest pain such as heart disease should be ruled out before making the diagnosis. Another kind of acid reflux, which causes respiratory and laryngeal signs and symptoms, is called laryngopharyngeal reflux (LPR) or “extraesophageal reflux disease” (EERD). Unlike GERD, LPR rarely produces heartburn, and is sometimes called silent reflux.

Prevention from Gastroesophageal Reflux

  • Certain foods and lifestyle are considered to promote gastroesophageal reflux, however most dietary interventions have little supporting evidence. 
  • Weight loss and elevating the head of the bed are generally useful. 
  • Avoid moderate exercise because it improves symptoms however in those with GERD vigorous exercise may worsen them. 
  • Stopping smoking and not drinking alcohol do not appear to result in significant improvement in symptoms. 
  • Avoidance of specific foods and eating before lying down should only be recommended to those in which they are associated with the symptoms. Foods that have been implicated include: coffee, alcohol, chocolate, fatty foods, acidic foods, and spicy foods

Treatment of Gastroesophageal Reflux

Medications

The primary medications used for GERD are proton-pump inhibitors, H2 receptor blockers and antacids with or without alginic acid.

Proton-pump inhibitors (PPIs) (such as omeprazole) are the most effective followed by H2 receptor blockers (such as ranitidine). If a once daily PPI is only partially effective they may be used twice a day. They should be taken a half to one hour before a meal. There is no significant difference between agents in this class. When these medications are used long term, the lowest effective dose should be taken. They may also be taken only when symptoms occur in those with frequent problems. H2 receptor blockers lead to roughly a 40% improvement.

The evidence for antacids is weaker with a benefit of about 10% (NNT=13) while a combination of an antacid and alginic acid (such as Gaviscon) may improve symptoms 60% (NNT=4).bMetoclopramide (a prokinetic) is not recommended either alone or in combination with other treatments due to concerns around adverse effects. The benefit of the prokinetic mosapride is modest.

Sucralfate has a similar effectiveness to H2 receptor blockers; however, sucralfate needs to be taken multiple times a day thus limiting it use. Baclofen, an agonist of the GABAB receptor, while effective, has similar issues of needing frequent dosing in addition to greater adverse effects compared to other medications.

Surgery

The standard surgical treatment for severe GERD is the Nissen fundoplication. In this procedure, the upper part of the stomach is wrapped around the lower esophageal sphincter to strengthen the sphincter and prevent acid reflux and to repair a hiatal hernia. It is only recommended in those who improve with PPIs. Benefits are equal to medical treatment in those with chronic symptoms. In addition, in the short and medium term, laparoscopic fundoplication improves quality of life compared to medical management. When comparing different fundoplication techniques, partial posterior fundoplication surgery is more effective than partial anterior fundoplication surgery.

Pregnancy

In pregnancy, dietary modifications and lifestyle changes may be attempted, but often have little effect. Calcium-based antacids are recommended if these changes are not effective. Aluminum- and magnesium-based antacids are also safe, as is ranitidine and PPIs.

Infants

Infants may see relief with changes in feeding techniques, such as smaller, more frequent feedings, changes in position during feedings, or more frequent burping during feedings. They may also be treated with medicines such as ranitidine or proton pump inhibitors. Proton pump inhibitors however have not been found to be effective in this population and there is a lack of evidence for safety.

Overtreatment

The use of acid suppression therapy is a common response to GERD symptoms and many patients get more of this kind of treatment than their individual case merits. The overuse of this treatment is a problem because of the side effects and costs which the patient will have from undergoing unnecessary therapy, and patients should not take more treatment than they need.

In some cases, a person with GERD symptoms can manage them by taking over-the-counter drugs and making lifestyle changes. This is often safer and less expensive than taking prescription drugs. Some guidelines recommend trying to treat symptoms with an H2 antagonist before using a proton-pump inhibitor because of cost and safety concerns.