Gastro-esophageal

reflux disease
(GERD)
Prepared by
Under supervision of

Prof Dr
 Introduction
Gastroesophageal reflux disease (GERD) is defined as ‘‘a condition
which develops when the reflux of stomach contents causes troublesome
symptoms and/or complications’ (Vakil et al., 2006).

The disease is highly prevalent, especially in developed countries,

affecting 18–27% of the North Americans, 8–25% of Europeans, 23% of
South Americans,11% of Australians, and 2–7% of Eastern Asians (El-
Serag et al., 2014).

This high prevalence impacts not only quality of life but also economy.
The burden of GERD in the USA may reach 9–10 billion dollars/year in
direct costs plus uncountable dollars in indirect costs due to decrease in
productivity and days off work (Joish et al., 2005).

The understanding of GERD pathophysiology is essential to determine

an optimal treatment of these patients. GERD pathophysiology is, however,
complex and multifactorial, determining a tailored and individual approach
for each case. Overall, it is due to a lack of balance between protective
mechanisms and aggressive chemical substances, between the valvular
mechanism and the trans-diaphragmatic pressure gradient (Herbella et al.,
2010 & Patti et al., 2015).

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 Successful treatment of GERD symptoms has been associated with
significant improvement in quality of life, including decreased physical pain,
increased vitality, physical and social function, and emotional wellbeing.
While GERD medications are not particularly expensive, the cost of treating
GERD patients has been deemed 2-fold more costly than comparable
individuals without GERD (Bloom et al., 2001).

Abstract

Definition and description of GERD:

Gastroesophageal reflux disease (GERD), as generally defined, is a

common condition that results from the reflux of gastric material through the
lower esophageal sphincter (LES) into the esophagus or oropharynx,
causing symptoms and/or injury to esophageal tissue. (Spechler et al.,
1992).

GERD can be classified relative to the presence or absence of erosions;

GERD symptoms without erosions on endoscopic examination constitute
nonerosive reflux disease (NERD), whereas GERD symptoms with erosions
constitute erosive esophagitis (EE). ( Katz et al., 2013).

Extraesophageal GERD syndromes can be categorized as conditions that

have an established association with GERD (cough, laryngitis, asthma,
dental erosions) and those that have only a proposed association
(pharyngitis, sinusitis, idiopathic pulmonary fibrosis, otitis media). ( Hunt et
al., 2013).

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Clinical features:

 Predisposing and risk factors

GERD is a sensorimotor disorder associated with impairment of the
normal antireflux mechanisms (e.g., lower esophageal sphincter
function, phrenicoesophageal ligament), with changes in normal
physiology (e.g., impaired esophageal peristalsis, increased
intragastric pressure, increased abdominothoracic pressure gradient)
or, very rarely, excess gastric acid secretion (Zollinger–Ellison
syndrome).

Eating and lifestyle

 An increase in GERD symptoms occurs in individuals who gain

weight (El-Serag et al., 2008).
 A high body mass index (BMI) is associated with an increased
risk of GERD (Goh et al ., 2004)
 High dietary fat intake is linked to a higher risk of GERD and
erosive esophagitis (EE) (El-Serag et al., 2005)
 Carbonated drinks are a risk factor for heartburn during sleep in
patients with GERD ( Fass et al., 2005)
 The role of coffee as a risk factor for GERD is unclear; coffee
may increase heartburn in some GERD patients (DiBaise et al.,
2003 ) , but the mechanism is unknown and it may be due to
caffeine, rather than coffee per se. Coffee is not a dominant risk
factor.
 The role of alcohol consumption as a risk factor for GERD is
unclear. Excessive, long-term use may be associated with

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 progression to esophageal malignancy, but this may be
independent of an effect of alcohol on GERD (Akiyama et al.,
2008 & Gunasekaran et al ., 2008)
 The role of smoking as a risk factor for GERD is unclear,
although like alcohol, it is associated with an increased risk of
malignancy (Nilsson et al., 2004 & Eslick et al., 2009)

Medication — certain medications may affect GERD:

 The treatment of comorbidities (e.g., with calcium channel blockers,

anticholinergics, and nonsteroidal anti-inflammatory drugs (NSAIDs)
may negatively affect GERD and its treatment (Moraes-Filho et al.,
2009)

Pregnancy:

 Heartburn during pregnancy usually does not differ from the classical
presentation in the adult population, but it worsens as pregnancy
advances. Regurgitation occurs with approximately the same
frequency as heartburn, and GERD in the first trimester is associated
with a number of altered physiological responses (Richter et al.,2005
& Keller et al., 2008)

Pathophysiology:

Gastroesophageal reflux is primarily a disorder of the lower

esophageal sphincter (LES) but there are several factors that may
contribute to its development. The factors influencing GERD are both
physiologic and pathologic. The most common cause is transient lower
esophageal sphincter relaxations (TLESRs). TLESRs are brief moments

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of lower esophageal sphincter tone inhibition that are independent of a
swallow (Herregods et al., 2015). While these are physiologic in nature,
there is an increase in frequency in the postprandial phase and they
contribute greatly to acid reflux in patients with GERD. Other factors
include reduced lower esophageal sphincter (LES) pressure, hiatal
hernias, impaired esophageal clearance, and delayed gastric emptying
(Ferriolli et al., 1998, Richter et al., 2000, Emerenziani et al.,
2005,and Herregods et al., 2015 ).

Clinical pictures:

The classic and most common symptom of GERD is heartburn.

Heartburn is a burning sensation in the chest, radiating toward the mouth,
as a result of acid reflux into the esophagus. However, only a small
percentage of reflux events are symptomatic. Heartburn is also often
associated with a sour taste in the back of the mouth with or without
regurgitation of the refluxate.

Notably, GERD is a common cause of non-cardiac chest pain

(Gastal et al., 1994 & Bredenoord et al., 2006). It is important to
distinguish between the underlying cause of the chest pain because of the
potentially serious implications of cardiac chest pain and varied
diagnostic and treatment algorithms based on etiology (Gastal et al.,
1994) .

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 Although classic symptoms of GERD are easily recognized,
extraesophageal manifestations of GERD are also common but not
always recognized. Extraesophageal symptoms are more likely due to
reflux into the larynx, resulting in throat clearing and hoarseness. It is not
uncommon for patients with GERD to complain of a feeling of fullness
or a lump in the back of their throat, referred to as globus sensation
(Tokashiki et al., 2010). Furthermore, acid reflux may trigger
bronchospasm, which can exacerbate underlying asthma, thereby leading
to cough, dyspnea, and wheezing (Irwin et al., 1993).

GERD symptoms should be considered as distinct from dyspepsia.

Dyspepsia is defined as epigastric discomfort, without heartburn or acid
regurgitation, lasting longer than one month. It can be associated with
bloating/epigastric fullness, belching, nausea, and vomiting. Dyspepsia is
an entity that may be managed differently from GERD and may prompt
endoscopic evaluation, as well as testing for H. pylori. ( Dent et al.,
2004).

Complications

Left untreated, GERD can result in several serious complications,

including esophagitis and Barrett’s esophagus. Esophagitis can vary
widely in severity with severe cases resulting in extensive erosions,
ulcerations and narrowing of the esophagus (Ronkainen et al., 2005).
Esophagitis may also lead to gastrointestinal (GI) bleeding. Upper GI
bleeding may present as anemia, hematemesis, coffee-ground emesis,
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melena, and when especially brisk, hematochezia. Chronic esophageal
inflammation from ongoing acid exposure may also lead to scarring and
the development of peptic strictures, usually presenting with the chief
complaint of dysphagia ( Richter et al., 2000).

Patients with persistent acid reflux may be at risk for Barrett’s

esophagus, defined as intestinal metaplasia of the esophagus. In Barrett’s
esophagus, the normal squamous cell epithelium of the esophagus is
replaced by columnar epithelium with goblet cells, as a response to acid
exposure ( Shaheen et al., 2009). Changes of Barrett’s esophagus may
extend proximally from the gastroesophageal junction (GEJ) and have
the potential to progress to esophageal adenocarcinoma, making early
detection very important in the prevention and management of malignant
transformation (Khademi et al., 2012).

Diagnosis

GERD is usually diagnosed clinically with classic symptoms and

response to acid suppression. Heartburn with or without regurgitation is
typically sufficient to suspect GERD, particularly when these symptoms
are worse postprandially or when recumbent (Dent et al., 2004). The
initiation of treatment with histamine type 2 (H2) receptor blockers or
proton pump inhibitors (PPIs) with subsequent cessation of symptoms is
considered diagnostic. In patients who respond to empiric treatment, in
the absence of alarm features or symptoms, no further workup is required
(Wang et al., 2005).

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 The most utilized diagnostic test for the evaluation of GERD and its
possible complications is the upper gastrointestinal endoscopy, or
esophagogastroduodenoscopy (EGD). The primary benefit of endoscopy
is direct visualization of the esophageal mucosa. This assists in diagnosis
of complications of GERD such as esophagitis, strictures and Barrett’s
esophagus. One endoscopic grading system of GERD severity is the Los
Angeles classification, graded from A to D, with D being the most severe
(Lundell et al., 1999).

Figure 1

Endoscopic view of Los Angeles grade D esophagitis (circumferential

esophageal erosions, ulceration, and inflammation)

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Figure 2. Endoscopic views of esophagitis grades. (A) Grade A—1 or
more mucosal breaks (arrow) no longer than 5 mm that do not extend
between the tops of two mucosal folds. (B) Grade B—1 or more mucosal
breaks (arrow) longer than 5 mm that do not extend between the tops of
two mucosal folds. (C) Grade C—1 or more mucosal breaks (arrows) that
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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 (arrows) that involve at least 75% of the esophageal
circumference.

Ambulatory pH monitoring is considered the gold standard in the

diagnosis of acid reflux. Ambulatory pH monitoring allows for the
objective detection of acid reflux events and correlation with symptoms.
This is particularly helpful in symptomatic patients with normal
endoscopic findings. Ambulatory pH testing can be completed with good
reproducibility (84–93%), sensitivity (96%), and specificity (96%)
(Wiener et al., 1988).

To complete the test, pH probes (catheter or wireless capsule) are

placed into the esophagus for 24 to 48 hours. Percent of time with an
esophageal pH of less than 4 is the primary parameter used in the
diagnosis of GERD. It has the benefit of detecting dynamic changes in
pH while upright and recumbent. Furthermore, pH probes record the
number of reflux events, the proximal extent of reflux, as well as the
duration of reflux events. Symptom correlation is also noted between
reflux and symptoms. This test can be performed on or off PPI therapy.

While it has some utility in evaluating patients with dysphagia, the

barium esophagram is a poor screening test for GERD. It has a very poor
sensitivity (26%) and specificity (50%) for mild esophagitis compared to
endoscopy. Reflux of barium often does not correlate well with reflux of

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acid in symptomatic patients, and in up to 20% of cases is positive in
normal individuals (Katz et al., 2013).

Treatment

GERD patients should be assessed for alarm features, as these

should prompt urgent endoscopic evaluation. If no alarm symptoms are
present, initial management of GERD should be geared toward lifestyle
modification. However, it is important to note that the majority of studies
on lifestyle and dietary changes in GERD have not been well powered.
Nevertheless, lifestyle changes remain first-line in management of
GERD with a primary goal of symptom reduction and improvement in
quality of life (Meining  et al., 2000 & DeVault  et al., 2005).

The only proven lifestyle modification for the management of

GERD is head of bed (HOB) elevation (Khan et al., 2012). Head of bed
elevation has been shown to decrease esophageal acid exposure and
esophageal clearance time with subsequent reduction in symptoms in
patients with supine GERD. In addition, is it advised that factors
contributing to the incidence of TLESRs should also be minimized or
avoided. These include smoking, heavy alcohol consumption, large
evening meals, nighttime snacks, and high dietary fat intake ( Meining et
al., 2009). Weight loss is strongly encouraged in overweight GERD
patients, but there is no documented benefit in those with normal weight
(Fraser-Moodie et al., 2009). Although obesity is a risk factor for
GERD, most bariatric surgeries exacerbate reflux. Additionally, all
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patients with GERD should avoid non-steroidal anti-inflammatory drugs
(NSAIDs) because of their role in disrupting physiologic mucosal
protection mechanisms.

Medication therapy for GERD is targeted at symptom reduction and

minimizing mucosal damage from acid reflux. While acid suppression is
successful in the treatment of GERD, there does not appear to be a clear
relationship between GERD severity and high gastric acid levels with the
exception being Zollinger-Ellison syndrome (Hirschowitz et al., 1991).

Many patients with heartburn try over-the-counter antacids prior to

seeking medical attention. The primary acid suppressive medications
include H2 blockers and proton pump inhibitors. H2 blockers decrease
gastric acid secretion by inhibiting histamine stimulation of the parietal
cell. Proton pump inhibitors work to decrease the amount of acid secreted
from parietal cells into the gastric lumen. H2 blockers have been shown
to have some symptomatic benefit above placebo, but in individuals
without contraindication, PPIs are the most effective therapy (Richter et
al., 2000). There is no clear role for prokinetic agents, such as
metoclopramide, in the treatment of GERD (Katz et al., 2013).

Proton pump inhibitors are the most potent class of antacid

medications. They are dosed once or twice daily and are most effective if
taken 30 to 60 minutes prior to meals. Many patients will have relapse of

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symptoms after the cessation of PPI, therefore lifelong therapy is often
required (Katz et al., 2013). Recently, there has been a rise in concern of
PPIs contributing to the development of bone fractures, electrolyte
deficiencies, infections e.g., Clostridium difficile, pneumonia), and renal
insufficiency (Dial et al., 2009 & Laine et al., 2009).

The use of anti-reflux surgery (fundoplication) has been

controversial. Studies show only minimal long-term symptomatic
improvements with surgery over PPI therapy, paired with an increased
incidence of dysphagia and dyspepsia. Patients who respond best to
surgery are those who also respond well to PPIs and therefore may be
managed medically. Conversely, PPI-refractory patients are unlikely to
have benefit from surgery (Katz et al., 2013). Approximately half of all
patients who undergo surgery eventually require surgical revision. Given
the near-negligible difference in efficacy between surgery and PPI and
the risk for postoperative complications and mortality, surgery should
only be reserved for select patients. Choosing the best candidates for anti-
reflux surgery remains a clinical challenge.

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Figure 3. Approach to gastroesophageal refl ux disease (PPI = proton
pump inhibitor, EGD = esophagogastroduodenoscopy).

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