Gastroesophageal reflux disease (GERD) occurs due to backflow of stomach acid into the esophagus. Heartburn is one of the common acid reflux and GERD symptoms.

GERD

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Overview

GERD, also known as gastroesophageal reflux disease, is a condition in which there is a backward flow of the stomach contents in the esophagus due to an incompetent lower esophageal sphincter. The presence of gastric acid in the esophagus determines the presentation of erosive esophagitis: inflammation of the esophagus, or a non-erosive disease. This is because gastric acid can damage the lining of the esophagus and produce an exclusive set of symptoms and complications<a href="#accordion">[1]</a>.

GERD is more common than you can imagine. Data proves that it is responsible for almost 5.6 million visits to physicians each year<a href="#accordion">[2]</a>.&nbsp;It has also been estimated that the western population of almost 10-20% experiences GERD symptoms every week, with 5% of the Asian population doing the same<a href="#accordion">[3]</a>.&nbsp;The prevalence of GERD seen in the United States was 18.1% to 27.8%<a href="#accordion">[1]</a>, whereas in Pakistan, it was 22.2% to 24%<a href="#accordion">[4]</a>.&nbsp;In an extensive meta-analysis study, it was seen that types of GERD are gender predominant as well and that women are more susceptible to exhibit symptoms of GERD as compared to men (16.7% vs 15.4% respectively)<a href="#accordion">[1]</a>.

Furthermore, it is crucial to understand that GERD majorly affects the quality of life. Everything from the sleep routine to the work routine is massively disturbed and becomes a reason for irritability, discomfort, and even <a href="https://www.merisehat.pk/disease/depression" target="_blank">depression</a><a href="#accordion">[5]</a>.&nbsp;This can have an indirect effect on the productivity of your workplace and a direct effect on your productivity. According to data collected in 2015, the indirect cost of decreased work productivity due to GERD and its complications was almost $75 billion<a href="#accordion">[2]</a>.

&nbsp;

Histopathology and Endoscopy have abled practitioners to classify GERD into the following three types based on their appearance:

<ol>
	<li>Non-Erosive Reflux Disease (NERD)</li>
	<li>Erosive Esophagitis</li>
	<li>Barrett Esophagus</li>
</ol>

Incidences of these different types are 60%-70% for NERD, 30% for Erosive Esophagitis, and 6-12% for <a href="https://www.merisehat.pk/disease/barretts-esophagus" target="_blank">Barrett Esophagus</a> respectively<a href="http://#accordion">[1]</a>.

&nbsp;

<h5>1. Non-Erosive Reflux Disease</h5>

According to the Montreal International Consensus, NERD was defined as a condition existing because of the backward flow of gastric contents causing serious reflux-related symptoms in the absence of esophageal erosion.

Earlier it was seen that almost half of the patients showed a normal esophagus upon performing endoscopy. Later on in European community-based studies, this number was estimated to be approximately 70%.&nbsp; It should also be kept in mind that NERD can turn into erosive esophagitis. A study led by Isolauri et al. showed that at baseline, 30 out of 50 patients had NERD but at follow-up, 17% of them had progressed into erosive esophagitis<a href="http://#accordion">[6]</a>.

Studies have shown that the mechanism of action of NERD is the transient lower esophageal sphincter (LES) relaxation. The relaxation opens the gateway between the stomach and esophagus and allows the retrograde flow of gastric contents. The distinct pathological feature seen in NERD is dilated intercellular spaces within the squamous epithelium, an ultrastructural abnormality that can be seen not only on transmission electron microscopy but also on light microscopy<a href="#accordion">[7]</a>.

Signs and symptoms of NERD include heartburn and acid regurgitation. Heartburn essentially means a burning sensation felt behind the breastbone rising toward the throat or the neck. Apart from this, classic symptoms of GERD can be seen in NERD but without the erosion of the esophageal mucosa<a href="http://#accordion">[8]</a>.

&nbsp;

<h5>2. Erosive Esophagitis</h5>

Esophagus is the part of your alimentary canal that connects your throat to the stomach. And adding the suffix &ldquo;itis&rdquo; in medical language means inflammation. Hence, it can be translated as the inflammation of the esophagus due to erosion or damage to its mucosal lining. This damage has everything to do with the acidic compositing of the gastric content flowing backward. It has been studied that 1% of the population goes through erosive esophagitis.

Different mechanisms of action contribute to erosive esophagitis (EE). The transient lower esophageal sphincter relaxation (LES) also plays a role in erosive esophagitis as it does in NERD. Moreover, people who have hiatal hernias are at a higher risk of reflux because of decreased LES tone, hence, causing erosive esophagitis. Hiatal hernia is when the upper part of your stomach moves to the chest cavity through your diaphragm. However, it is not always LES that causes this condition. If the esophageal movement is decreased or saliva production is altered, i.e., if anything that can help defend the mucosal lining of the esophagus is compromised, we can see the manifestation of EE<a href="#accordion">[9]</a>.

&nbsp;

<h5>3. Barrett Esophagus</h5>

Barrett esophagus (BE) is known to be a precancerous lesion that can transform into adenocarcinoma of the esophagus. BE is a condition in which the inner lining of the esophagus is changed into a type of lining we can find in our intestines<a href="http://#accordion">[10]</a>.

Another way to define BE is the replacement of the distal esophageal squamous epithelium with metaplastic columnar epithelium. Metaplasia is changing of one tissue into another. Hence, many competent authorities including The American Gastroenterological Association (AGA), the American College of Gastroenterology (ACG), and the European Society of Gastrointestinal Endoscopy (ESGE) stated that the metaplasia of the esophageal tissue in intestinal tissue was crucial for the condition to be labeled as BE. Adopting this prerequisite has also helped clinicians to have a more cost-efficient approach to the care of patients<a href="#accordion">[10]</a>.

For diagnosing BE, an endoscopy is done. A BE&rsquo;s endoscopic images would look red and thickened as compared to the normal esophagus&rsquo;s endoscopy which would appear to be flat and white<a href="#accordion">[11]</a>.&nbsp;Endoscopy is a procedure in which an instrument is introduced into the human body to give medical practitioners a better idea of what is happening inside. Endoscopy is now being used to take samples for biopsies as well. However, a simple endoscopy procedure is inadequate and a biopsy confirming the existence of intestinal metaplasia is also required in BE. Another diagnostic modality that helps in diagnosing BE is enhanced magnification endoscopy (EME), which is a combination of using acetic acid and magnifying endoscopy. Studies prove that EME is an adequate screening method but due to its low specificity, a biopsy would still be needed<a href="http://#accordion">[10]</a>.

BE has also shown an association with non-resolving GERD. Signs and symptoms of BE include heartburn, regurgitation of gastric contents, a sensation of food stuck in your esophagus, constant sore throat, sour taste in your mouth or bad breath, and unintentional weight loss<a href="#accordion">[12]</a>.

&nbsp;

There are no screening guidelines for GERD,&nbsp;yet<a href="http://#accordion">[14]</a>. However, as the causes of GERD suggest, there can be a workaround. A detailed history is the key to understanding the patient. In the past detailed assessing equipment did not exist for a very long time, and it was solely on the basis of history that helped practitioners reach a probable diagnosis and start an empiric treatment.

Though there is no such screening test for GERD, a detailed history in limited resource based primary care centers can point your doctor in the right direction. Information on your dietary habits, recurrent conditions, chest pain, and burning sensation in the throat may all be helpful.

&nbsp;

Diagnosis

There is no gold standard for GERD, but there are different modalities through which GERD can be efficiently identified and treated. The following are the different diagnostic techniques: 
&nbsp;

<h5>1. Proton Pump Inhibitors (PPI) Trial</h5>

PPI is a drug that blocks gastric acid secretion by inhibiting the hydrogen-ATPase pump. This causes a significant decrease in the acid component of the gastric content, hence, relieving the patient of the symptoms. Doctors prescribe the patient a PPI after taking a detailed history and looking at the signs. If all the prerequisites are checked, empiric treatment with PPI can take away the symptoms patient was feeling, hence confirming the diagnosis.

However, to be able to start with this trial, your health practitioner has to make sure that the following symptoms are not reported:

<ul>
	<li>Dysphagia (difficulty in swallowing)</li>
	<li>Odynophagia (pain while swallowing)</li>
	<li><a href="https://www.merisehat.pk/disease/anemia" target="_blank">Anemia </a>(decreased Red Blood Cells)</li>
	<li>Weight loss</li>
	<li>Hematemesis (blood in vomit)<a href="#accordion">[1]</a> 
	&nbsp;</li>
</ul>

<h5>2. Esophagogastroduodenoscopy (EGD)</h5>

EGD is a daycare procedure, which means that you can have the procedure and go home the same day, which helps your healthcare practitioner to have a look at what is going inside your esophagus, stomach, and duodenum (part of your small intestine). EGD is usually done to see if GERD has made some drastic changes to the part of your digestive tract. Complications that the doctors look out for are Esophageal strictures, Adenocarcinoma, and BE. The American College of Gastroenterology (ACG) also recommends that a patient should be tested for H. Pylori, if the patients are positive for symptoms of GERD. H. Pylori is a gram-negative bacteria that attacks your stomach and causes the infamous peptic ulcer<a href="#accordion">[1</a>]<a href="#accordion">[15]</a>.

&nbsp;

<h5>3. Ambulatory Esophageal pH Monitoring</h5>

As PPIs are highly effective against GERD symptoms, it becomes hard for clinicians to find the root cause. This specific diagnostic modality helps clinicians to see how the distal esophagus is exposed to gastric acid. Many clinicians consider Ambulatory Esophageal pH Monitoring as the gold standard for diagnosing GERD. It can also be useful in patients who exhibit extra-esophageal symptoms of GERD such as chronic cough and even asthma<a href="#accordion">[1]</a><a href="#accordion">[16]</a>.

The modality holds such importance that the current practice guidelines emphasize having mandatory preoperative ambulatory pH monitoring in patients that do not show any evidence of EE. 
&nbsp;

Treatment

An efficient treatment for GERD includes approaches that help alleviate symptoms and prevent the development of complications. The treatment options available for GERD are according to the severity of the symptoms or failure of a previous treatment. The following are the treatments practiced:

&nbsp;

<h5>1. Changing Your Lifestyle</h5>

The most essential part of GERD treatment is revamping your lifestyle choices. As discussed earlier, GERD can be developed due to many reasons other than the LES being mechanically damaged. The biggest influencing factor is the dietary habit. Patients should be counseled to make healthier dietary choices. Hence, a diet with fewer spices and fried items will always be crucial in the treatment process. Furthermore, food items like chocolates, carbonated beverages, and caffeine should be avoided. Moreover, weight loss for patients with high BMI is extremely important. Weight gain increases the intra-abdominal pressure and forces the LES to open. It is also recommended that the last meal should be consumed at least 3 hours before sleeping. This allows ample time for food to travel down further down in the digestive tract and not put an excessive burden on the LES. Studies prove that proper restful sleep causes suppression of the transient lower esophageal relaxation, hence, treating the root cause.

&nbsp;

<h5>2. Medical Therapy</h5>

Patients who do not respond to the changes made in their lifestyle are prescribed medications. Drugs that are used in GERD are the following:

<ul>
	<li>PPI: Proton pump inhibitors act against the hydrogen ATPase pump inhibitor of the parietal cells. These cells are found in the fundus of the stomach and secrete gastric acid. Hence, these drugs decrease gastric acid secretion. Examples of PPIs include omeprazole and esmoprazole.</li>
	<li>H2RA (Histamine Receptor Antagonist): These drugs act on the histamine receptors of the parietal cells. These drugs prevent the acid-making cells of the stomach to respond to a chemical called histamine. The U.S. FDA-approved H2RA agents are famotidine and cimetidine, while the other non-approved drugs are ranitidine and nizatidine. H2RA is particularly favored for patients with nocturnal symptoms.</li>
	<li>Antacids: Antacids are essentially neutralizing agents and reduce the potency of gastric acid. These drugs inhibit pepsin which is a proteolytic enzyme secreted by the chief cells in the stomach. Pepsin helps increase stomach acidity.</li>
</ul>

Out of all the medical therapies, PPI has been acclaimed the most. According to the ACG recommendations, PPI should be prescribed once daily before meals.

&nbsp;

<h5>3. Surgical Therapy</h5>

If patients do not respond to medical therapy or the patient gets recurring GERD, surgical intervention is needed. Different surgical procedures can be used:

<ul>
	<li>Laparoscopic Toupet Fundoplication: It is used to strengthen the esophageal sphincter. This is a 270-degree warp around the esophagus, creating a tight junction between the stomach and esophagus<a href="#accordion">[18]</a>.</li>
	<li>Laparoscopic Nissen Fundoplication: This is the gold standard procedure considered for GERD. The procedure includes the surgeon creating a sphincter at the lower end of the esophagus to prevent acid reflux<a href="#accordion">[17]</a>.</li>
</ul>

<h5>&nbsp;</h5>

<h5>4. Endoluminal Therapy</h5>

This is a relatively new surgical procedure that is less invasive than a standard fundoplication. It includes magnetic sphincter augmentation (MSA) and trans-oral incision-less fundoplication (TIF). Studies show that TIF was an effective long-term treatment whereas MSA was comparable to Nissen fundoplication, if not better, for short-term outcomes. The idea of TIF is the same as Toupet fundoplication; a 270-degree wrap around the esophagus, but in an incision-less setting, whereas, MSA involves fixing the sphincter with the use of magnets<a href="#accordion">[1]</a>.

&nbsp;

GERD can cause inflammation of the esophageal lining and chronically, this can lead to serious complications. Following are complications can be seen with long standing GERD:

<ul>
	<li>Esophageal Strictures: The LES gets damaged by gastric acid. This structurally changes the sphincter by scarring it. This narrows down the lumen and makes it difficult to swallow food.</li>
	<li>Esophageal Ulcer: Acid from the stomach can slough off the esophageal tissue because of its erosive property. An <a href="https://www.merisehat.pk/disease/peptic-ulcer-disease-pud" target="_blank">ulcer </a>can cause bleeding and odynophagia.</li>
	<li>Barrett&rsquo;s Esophagus: BE, as discussed above, is a precancerous lesion that is the result of long standing GERD. BE has the potential to progress into adenocarcinoma of the esophagus<a href="#accordion">[22]</a>.</li>
</ul>

&nbsp;

Risk Factors

Chances of getting GERD increase if you have the following associations:

<ul>
	<li>A High BMI Or Being Overweight. These conditions place unnecessary high pressure on the abdomen.</li>
	<li>Excess Alcohol Intake&nbsp;since it can weaken the defensive mucosa of the esophagus.</li>
	<li>Asthmatic, Hypertensive, Or Depressed Patients are at a higher risk of GERD since the medications involved in their treatment can cause GERD.</li>
	<li>Having Scleroderma. Esophageal muscles are seen to be weakened in this condition.</li>
	<li>Smoking. It decreases the efficiency of the LES by weakening the muscle<a href="#accordion">[19]</a>.</li>
</ul>

&nbsp;

Although GERD can even complicate into a precancerous stage called Barrett&#39;s esophagus, it can be easily prevented. Following are the ways that can help you stay away from the disease:

<ul>
	<li>Maintenance Of A Healthy Weight: Obesity increases the intra-abdominal pressure, hence predisposing to GERD.</li>
	<li>Eating Small Frequent Meals: Smaller portions of food do not cause a drastic increase in the amount of gastric acid produced in the stomach. Contrastingly, heavy meals can cause a drastic increase of gastric acid production anlongside causing fullness of the stomach (raised abdominal pressure).</li>
	<li>Healthy Diet: A healthy diet should be taken, free of fried food and full fat dairy products. A low spice profile should also be ensured.</li>
	<li>Eating 3 Hours Before Sleeping: It is recommended that the last meal should be consumed almost 3 hours before bedtime, allowing more time for food to digest.</li>
	<li>Avoid Tight Clothes: Wearing tight clothes can increase pressure around your waist and, consequently, increase the intra-abdominal pressure.</li>
	<li>Elevation Of Headrest: Elevating the head of your bed 6-8 inches allows gravity to work its charm and prevent the gastric content from flowing in retrograde direction<a href="#accordion">[13]</a>.</li>
</ul>

&nbsp;

In some GERD patients, the symptom of heartburn persists despite treatment with proton pump inhibitors (PPI) and recent research suggests that perhaps these patients have been misdiagnosed with GERD. Heartburn can be seen in diseases like Achalasia, Megaesophagus, or different kinds of Esophagitis. Hence, it is important to rule out these causes before diagnosing a patient with PPI Refractory GERD (a condition wherein GERD symptoms persist despite PPI treatment). There is also evidence to believe that patients with PPI Refractory GERD might benefit more from surgical interventions<a href="#accordion">[20]</a><a href="#accordion">[21]</a>.

&nbsp;

Key Points

<ul>
	<li>GERD, also called gastroesophageal reflux disease, is the backward flow of the stomach contents in the esophagus due to the lower esophageal sphincter failing to function properly.</li>
	<li>GERD is responsible for almost 5.6 million visits to physicians each year. The prevalence of GERD in the United States was 18.1% to 27.8% and 22.2% to 24% in Pakistan.<a href="https://www.ncbi.nlm.nih.gov/books/NBK441938/" style="letter-spacing: 0.2px; background-color: rgb(255, 255, 255);">&nbsp;</a></li>
	<li>Based on their phenotype, there are 3 types of GERD, erosive esophagitis, <a href="https://www.merisehat.pk/disease/barretts-esophagus" target="_blank">Barrett&#39;s esophagus</a>, and non-erosive reflux disease.</li>
	<li>Causes of GERD include increased abdominal pressure, increased intake of fried and spicy foods, and certain medications. Diseases like scleroderma and hiatal <a href="https://www.merisehat.pk/disease/hernia#diagnosis-5984" target="_blank">hernia </a>are also some of the causes of GERD.</li>
	<li>pH monitoring, esophagogastroduodenoscopy, and PPI trials are used to diagnose GERD.</li>
	<li>Treatment of GERD includes lifestyle modification, medical therapy including PPIs and H2RAs along with surgical interventions. Every next mode of treatment is applied if the previous one fails.</li>
	<li>If not treated adequately, GERD can cause serious complications like Barrett&rsquo;s esophagus, esophageal ulcer, and esophageal strictures.</li>
	<li>Smoking, having a high BMI, or consuming excess alcohol are the risk factors involved, and preventing them can help stay away from GERD.</li>
	<li>Latest research has informed clinicians that not every heartburn is associated with GERD and can be due to conditions like esophagitis, megaesophagus, and hiatal hernia.</li>
</ul>

&nbsp;

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[2] Andrew Young, Mythri Anil Kumar, Prashanthi N. Thota Cleveland Clinic Journal of Medicine Apr 2020, 87 (4) 223-230.

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[5] Santos-Longhurst A. Gerd and anxiety: Is there a connection? Healthline.

[6] Hershcovici, Tiberiu, and Ronnie Fass. “Nonerosive Reflux Disease (NERD) - An Update.” Journal of neurogastroenterology and motility vol. 16,1 (2010): 8-21.

[7]  Long, J D, and R C Orlando. “Nonerosive reflux disease.” Minerva gastroenterologica e dietologica vol. 53,2 (2007): 127-41.

[8] Fass R, Dickman R. Nonerosive reflux disease. Nature News.

[9] Antunes C, Sharma A. Esophagitis. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.

[10] Zhang, Lu et al. “Barrett's Esophagus and Intestinal Metaplasia.” Frontiers in oncology vol. 11 630837.

[11] Barrett's esophagus. Mayo Clinic.

[12] Barrett's esophagus: What is it, symptoms, treatment &amp; tests. Cleveland Clinic.

[13] Gerd (chronic acid reflux): Symptoms, treatment, &amp; causes. Cleveland Clinic.

[14] Screening for gastroesophageal reflux disease (GERD). Winchester Hospital.

[15] Upper Gi Endoscopy. Upper GI Endoscopy | Johns Hopkins Medicine.

[16] Tutuian, Radu. “Update in the diagnosis of gastroesophageal reflux disease.” Journal of gastrointestinal and liver diseases : JGLD vol. 15,3 (2006):

[17] Nissen fundoplication: What is it, procedure details &amp; recovery. Cleveland Clinic.

[18] Stomach. Surgical Weight Loss Specialists Weight Loss &amp; General Surgery Salt Lake City UT.

[19] Risk factors for gastroesophageal reflux disease (GERD). Winchester Hospital.

[20] Robinson E. New research could change how clinicians diagnose, treat Unmanaged Heartburn. OHSU News.

[21] Azzam, Rimon Sobhi. “ARE THE PERSISTENT SYMPTOMS TO PROTON PUMP INHIBITOR THERAPY DUE TO REFRACTORY GASTROESOPHAGEAL REFLUX DISEASE OR TO OTHER DISORDERS?.” Arquivos de gastroenterologia vol. 55Suppl 1,Suppl 1 (2018): 85-91.