Gastroesophageal
Reflux Disease
S1
GERD is one of the most prevalent
gastrointestinal disorders. Population-based studies show that up to 15% of
individuals have heartburn and/or regurgitation at least once a week and 7%
have symptoms daily
Background
Gastroesophageal
reflux is a normal physiological phenomenon experienced intermittently by most
people, particularly after a meal.
Gastroesophageal reflux
disease (GERD) 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).
The cumulative effects of GER depend on the
amount of refluxed material per episode, the frequency of reflux episodes, the
rate of clearance of the esophagus by gravity and peristaltic contraction, and
the rate of neutralization of gastric acid by salivary secretion.
Pathophysiology
The
physiological and anatomical factors that prevent the reflux of gastric juice
from the stomach into the esophagus include the following:
·
The lower esophageal sphincter (LES) must have a normal length and
pressure and a normal number of episodes of transient relaxation (relaxation in
the absence of swallowing).
·
The gastroesophageal junction must be located in the abdomen so that the
diaphragmatic crura can assist the action of the LES, thus functioning as an
extrinsic sphincter. The presence of a hiatal hernia disrupts this synergistic
action and can promote reflux.
·
Esophageal clearance must be able to neutralize the acid refluxed
through the LES. (Mechanical clearance is achieved with esophageal peristalsis.
Chemical clearance is achieved with saliva.)
·
The stomach must empty properly.
Abnormal gastroesophageal
reflux is caused by the abnormalities of one or more of the following
protective mechanisms:
·
A functional (frequent transient LES relaxation) or mechanical
(hypotensive LES) problem of the LES is the most common cause of GERD (surgical
damage to the LES, and esophagitis, scleroderma-like diseases, myopathy
associated with chronic intestinal pseudo-obstruction, incompetence of the
diaphragmatic crural muscle).
·
Certain foods (eg, coffee, alcohol), medications (eg, calcium channel
blockers, nitrates, beta-blockers, sildenafil), or hormones (eg, progesterone)
can decrease the pressure of the LES.
·
Obesity is a contributing factor in GERD, probably because of the
increased intra-abdominal pressure. Some studies have shown that GERD is highly
prevalent in patients who are morbidly obese and that a high body mass index
(BMI) is a risk factor for the development of GERD. The
mechanism by which a high BMI increases esophageal acid exposure is not
completely understood. Increased intragastric pressure and gastroesophageal
pressure gradient, incompetence of the LES, and increased frequency of
transient LES relaxations may all play a role in the pathophysiology of the
disease in patients who are morbidly obese.
Race
·
White males are at a greater risk for Barrett esophagus and
adenocarcinoma than other populations.
Sex
·
No sexual predilection exists. GERD is as common in men as in women.
·
The male-to-female ratio for esophagitis is 2:1-3:1. The male-to-female
ratio for Barrett esophagus is 10:1.
Age
·
GERD occurs in all age groups.
·
The prevalence of GERD increases in people older than 40 years.
S2
CLINICAL PICTURE
History
GERD
can cause typical (esophageal) symptoms or atypical (extraesophageal) symptoms.
However, a diagnosis of GERD based on the presence of typical symptoms is
correct in only 70% of patients.
Typical (esophageal) symptoms include the following:
o
Heartburn is the most common typical symptom of GERD. Heartburn is felt as a
retrosternal sensation of burning or discomfort that usually occurs after
eating or when lying down or bending over.
o
Regurgitation is an effortless return of gastric and/or esophageal contents into the
pharynx. Regurgitation can induce respiratory complications if gastric contents
spill into the tracheobronchial tree.
o
Dysphagia occurs in approximately one third of patients because of a mechanical
stricture or a functional problem (eg, nonobstructive dysphagia secondary to
abnormal esophageal peristalsis). Patients with dysphagia experience a
sensation that food is stuck, particularly in the retrosternal area. Persistent dysphagia suggests development of
a peptic stricture. Most patients with peptic stricture have a history of
several years of heartburn preceding dysphagia. However, in one-third of
patients, dysphagia is the presenting symptom. Rapidly progressive dysphagia
and weight loss may indicate the development of adenocarcinoma in Barrett's esophagus.
o
Bleeding
occurs due to mucosal erosions or Barrett's ulcer.
o
Many patients with GERD remain asymptomatic or self-treated and
do not seek attention until severe complications occur.
S3. Atypical (extraesophageal)
symptoms
include the following:
o
Coughing and/or wheezing are respiratory symptoms (chronic cough,
bronchoconstriction, pharyngitis, laryngitis, bronchitis, or pneumonia,
pulmonary fibrosis, chronic asthma) resulting from the aspiration of gastric
contents into the tracheobronchial tree or from the vagal reflex arc producing
bronchoconstriction. Approximately 50% of patients who have GERD-induced asthma
do not experience heartburn.
o Hoarseness results from irritation of
the vocal cords by gastric refluxate. Hoarseness is often experienced by patients in the morning.
o
Reflux is the most common cause of noncardiac chest pain,
accounting for approximately 50% of cases. Patients can present to the
emergency department with pain resembling a myocardial infarction.
Approximately 50% of patients
with gastric reflux develop esophagitis. Esophagitis is classified into
the following 4 grades based on its severity:
o Grade I - Erythema
o Grade II - Linear nonconfluent erosions
o Grade III - Circular confluent erosions
o
Grade IV - Stricture or Barrett esophagus (Barrett esophagus is thought
to be caused by the chronic reflux of gastric juice into the esophagus. Barrett
esophagus occurs when the squamous epithelium of the esophagus is replaced by
the intestinal columnar epithelium. Barrett esophagus is present in 8-15% of
patients with GERD and may progress to adenocarcinoma.
Physical
Noncontributory,
absence of special objective data.
DIFFERENTIAL
DIAGNOSIS
1.
Achalasia. Achalasia
is a primary esophageal motility disorder characterized
by failure of a hypertensive LES to relax and the absence of esophageal
peristalsis. These abnormalities cause a functional obstruction at the
gastroesophageal junction.
2.
Cholelithiasis. Because
they are common, gallstones often coexist with other gastrointestinal
conditions. Little evidence suggests that gallstones cause chronic abdominal
pain, heartburn, postprandial distress, bloating, flatulence, constipation, or
diarrhea.
3.
Coronary Artery Atherosclerosis. Reflux
is the most common cause of noncardiac chest pain, accounting for approximately
50% of cases. Patients can present to the emergency department with pain
resembling a myocardial infarction. Reflux should be ruled out (using
esophageal manometry and 24-h pH testing if necessary) once a cardiac cause for
the chest pain has been excluded. Alternatively, a therapeutic trial of a
high-dose proton pump inhibitor (PPI) can be tried.
4.
Esophageal Cancer. GERD is the most common predisposing factor
for adenocarcinoma of the esophagus. 10-15% of patients who undergo endoscopy
for evaluation of GERD symptoms are found to have Barrett epithelium.
Adenocarcinoma may develop in these patients, representing the last event of a
sequence that starts with the development of GERD and progresses to (Barrett)
metaplasia, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma. The
risk of adenocarcinoma among patients with Barrett metaplasia has been
estimated to be 30-60 times that of the general population.
·
Dysphagia is the most common presenting symptom. Dysphagia is initially experienced for
solids, but eventually it progresses to include liquids.
·
Weight loss is the second most common symptom and
occurs in more than 50% of people with esophageal carcinoma.
·
Pain can be felt in the epigastric or retrosternal
area. It can also be felt over bony structures, representing a sign of
metastatic disease.
·
Hoarseness caused by invasion of the recurrent
laryngeal nerve is a sign of unresectability.
·
Respiratory symptoms can be caused by aspiration of
undigested food or by direct invasion of the tracheobronchial tree by the
tumor.
5. Esophageal Spasm. Etiology
of esophageal spasm is unknown. Theories include gastric reflux or a primary
nerve or motor disorder. Because of the similarity of symptoms of reflux
disease and esophageal spasm, many patients may be misdiagnosed with reflux. Furthermore, reflux and spasm can
occur concomitantly.
7. Irritable Bowel Syndrome. Irritable
bowel syndrome (IBS) is a functional GI disorder characterized by abdominal
pain and altered bowel habits in the absence of specific and unique organic
pathology.
ADDITIONAL
INVESTIGATIONS
I. Lab Studies
·
Laboratory tests are seldom useful in establishing a diagnosis of GERD.
II. Imaging Studies
1. Barium esophagogram
o
Barium esophagogram is particularly important for patients who
experience dysphagia.
o
Barium esophagogram can show the presence and location of a stricture
and the presence and shape of a hiatal hernia.
2. Esophagogastroduodenoscopy (Upper endoscopy)
o
Esophagogastroduodenoscopy (EGD) identifies the presence and severity of
esophagitis and the possible presence of Barrett esophagus.
o
EGD also excludes the presence of other diseases (eg, peptic ulcer) that
can present similarly to GERD.
o
Although EGD is frequently performed to help diagnose GERD, it is not
the most cost-effective diagnostic study because esophagitis is present in only
50% of patients with GERD.
III. Other tests
o
Esophageal manometry defines the function of the LES and the esophageal
body (peristalsis).
o
Esophageal manometry is essential for correctly positioning the probe
for the 24-hour pH monitoring.
2.
Ambulatory 24-hour pH monitoring
·
Ambulatory 24-hour pH monitoring is the criterion standard in
establishing a diagnosis of GERD with a sensitivity of 96% and a specificity of
95%.
·
Ambulatory 24-hour pH monitoring quantifies the gastroesophageal reflux
and allows a correlation between the symptoms of reflux and the episodes of
reflux.
·
Patients with endoscopically confirmed esophagitis do not need pH
monitoring to establish a diagnosis of GERD.
Indications for esophageal manometry and prolonged pH
monitoring
1. Persistence of symptoms while
taking adequate antisecretory therapy, such as PPI therapy.
2. Recurrence of symptoms after
discontinuation of acid-reducing medications.
3. Investigation of atypical
symptoms, such as chest pain or asthma, in patients without esophagitis.
4. Confirmation of the diagnosis
in preparation for antireflux surgery.
3. Radionuclide measurement of gastric emptying
·
Although delayed gastric emptying is present in as many as 60% of
patients with GERD, this emptying is usually a minor factor in the pathogenesis
of the disease in most patients (except in patients with advanced diabetes
mellitus or connective tissue disorders).
·
Patients with delayed gastric emptying typically experience postprandial
bloating and fullness in addition to other symptoms.
TREATMENT
Medical Care
S5
Treatment
is a stepwise approach. The goals are to control symptoms, to heal esophagitis,
and to prevent recurrent esophagitis or other complications. The treatment is
based on lifestyle modification and control of gastric acid secretion.
I.
Lifestyle modifications include the
following:
·
Losing
weight (if overweight)
·
Avoiding alcohol, chocolate, citrus juice, and tomato-based products
·
Avoiding
large meals
·
Waiting 3 hours after a meal before lying down
·
Elevating the head of the bed 20 cm
II. Pharmacologic
therapy
S6.
o
Antacids were the standard treatment in the 1970s and are still
effective in controlling mild symptoms of GERD. Antacids should be taken after
each meal and at bedtime.
o
Histamine H2 receptor antagonists are the first line agents for patients
with mild-to-moderate symptoms and grades I-II esophagitis. Histamine H2
receptor antagonists are effective for healing only mild esophagitis in 70-80%
of patients with GERD and for providing maintenance therapy to prevent relapse.
(cimetidine, 300 mg; ranitidine, 150
mg bid; famotidine, 20 mg bid; nizatidine, 150 mg bid)
o
Additional H2 blocker therapy has been reported to be useful in patients
with severe disease (particularly those with Barrett esophagus) who have
nocturnal acid production.
o
PPIs are the most powerful medications available. They should be used
only when GERD has been objectively documented. PPIs work by blocking the final
step in the H+ ion secretion by the parietal cell. Omeprazole (20 mg/d), lansoprazole (30 mg/d), pantoprazole (40
mg/d), esomeprazole (40 mg/d), or rabeprazole (20 mg/d) for 8 weeks can
heal erosive esophagitis in up to 90% of patients. The drug is taken 15 to 30
min before breakfast and can be maintained indefinitely. Refractory patients
can double the dose and administer it twice a day before meals.
They have few adverse effects
and are well tolerated for long-term use. However, recent data have shown that
PPIs can interfere with calcium homeostasis and aggravate cardiac conduction
defects. They have also been responsible for hip fracture in postmenopausal
women.
o
Prokinetic agents improve the motility of the esophagus and stomach. The
prokinetic drugs include bethanechol,
metoclopramide, and cisapride. Bethanechol
is a cholinergic antagonist that causes increased LES pressure, peristalsis,
and salivary flow. However, this agent is contraindicated in patients with
asthma. Metoclopramide is a
dopamine antagonist that may improve gastric emptying but is associated with
extrapyramidal side effects. Cisapride
has been taken off the market because of significant drug-drug interactions
leading to dysrhythmias. These agents are somewhat effective but only in
patients with mild symptoms; other patients usually require additional
acid-suppressing medications, such as PPIs. Long-term use of prokinetic agents
may have serious, even potentially fatal, complications and should be
discouraged.
III. Surgical Care
Approximately
80% of patients have a recurrent but nonprogressive form of GERD that is
controlled with medications. Other 20% of patients have a progressive form of
the disease and may develop severe complications. For patients who develop
complications, surgical treatment should be considered at an earlier stage to
avoid the serious consequences.
Indications for fundoplication
include the following:
·
Patients with symptoms that are not completely controlled by PPI therapy
can be considered for surgery.
·
Surgery can also be considered in patients with well-controlled disease
who desire definitive, one-time treatment.
·
The presence of Barrett esophagus is an indication for surgery.
·
The presence of extraesophageal manifestations of GERD: respiratory
manifestations; ear, nose, and throat manifestations; dental manifestations.
·
Young
patients.
·
Poor
patient compliance to medications
·
Postmenopausal
women with osteoporosis
·
Patients
with cardiac conduction defects
·
Cost of
medical therapy
The main surgical method is Laparoscopic
fundoplication .
Laparoscopic fundoplication is
performed under general endotracheal anesthesia. The
fundus of the stomach is wrapped around the esophagus to create a new valve at
the level of the gastroesophageal junction.
Laparoscopic fundoplication
lasts 2-2.5 hours. The hospital stay is approximately 2 days. Patients resume regular activities within 2-3
weeks.
Approximately 92% of patients
obtain resolution of symptoms after undergoing laparoscopic fundoplication.
