WHAT PREVENTS GASTROESOPHAGEAL REFLUX (GER) AND GERD?
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3. WHEN DOES GERD OCCUR?
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4. ACID AND NONACID REFLUX
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5. CLINICAL RISK FACTORS FOR GERD
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6.
DAMAGE CAUSED BY REFLUX
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7. SYMPTOMS OF GERD
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8. DIAGNOSIS OF GERD
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9. TREATMENT OPTIONS FOR GERD
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10. APPROACH TO MANAGEMENT OF GERD
Mechanism of disease, Risk factors,
Clinical spectrum, Diagnosis and Treatment
Raj K Goyal, MD
A. WHAT IS GERD?
Gastroesophageal Reflux Disease (GERD)
includes a spectrum of diseases caused by reflux or backflow of stomach
contents into the esophagus and then into the throat and the mouth. Reflux of
acid causes inflammation in the esophagus, throat and the lungs.
Consequences of esophageal inflammation
include peptic esophagitis, ulcer, scarring or stricture, and columnar cell
metaplasia (Barrett’s esophagus). Invasion of refluxed material above the
esophagus causes pharyngitis, laryngitis, pulmonary aspiration and oral
manifestations.
B. HOW COMMON IS GERD?
GERD is a very common
malady. Heartburn is a symptom of esophagitis that is only one manifestation
of GERD; and a Gallop poll survey revealed that
7% of the population experiencedheartburn symptoms daily, 14% weekly, and
44% monthly. Clearly, GERD is one of the very common clinical disorders.
2. WHAT PREVENTS GASTROESOPHAGEAL REFLUX (GER) AND GERD?
A. TENDENCY TO REFLUX IS NORMAL
Occasional GER is normal and occurs in all
of us because normal stomach and esophageal pressure gradients favor esophageal
reflux. The normal gastric pressure is higher than esophageal pressure.
Moreover, swallowed food is normally carried rapidly through the esophagus but
is stored in the stomach for acid digestion for several hours. Thus the stomach
provides a large reservoir of acid and food that can reflux into the esophagus.
B. DEFENCES AGAINST REFLUX
Excessive GER is prevented normally by
elaborate antireflux mechanisms that provide barriers to reflux. These barriers
keep reflux episodes to a minimum and prevent development of GERD. The
antireflux mechanisms include: 1) anatomic configuration of the gastroesophageal
junction; 2) esophageal sphincters; and 3) diaphragmatic sling in the
esophageal hiatus.
The esophagus is a narrow muscular pipe,
about 20 cm long in adults that is located in the posterior part of the
chest. It is a continuation of the throat (pharynx) that passes
through the chest and enters the abdomen through an opening in the diaphragm to
open into the stomach. The anatomy of the gastroesophageal junction is
specialized to provide an antireflux barrier (see Figure 1). First of all, the
lowermost part of the esophagus is located below the diaphragm, in the
abdominal cavity. The abdominal segment is kept closed by higher abdominal
pressure thus preventing GER. The esophagus enters the stomach at an angle
(called angle of His) and into the stomach at a point below the dome (fundus)
of the stomach. This configuration helps avoid GER. Moreover, there
is a flap of mucosa that arises from the region of the angle of His and covers
the esophageal opening like a valve. The gastric sling fibers contribute to the
angle if His and are present at the base of the valve. Contraction of the
gastric sling fibers accentuate the angle and enforce action of the mucosal
valve to close the esophageal opening and avoid reflux.
At either end of the wall of the esophagus
is specialized to form sphincters or valve like barriers to flow. The upper
esophageal sphincter (UES or pharyngoesophageal sphincter) is located at
junction the esophagus with the pharynx. The lower esophageal
sphincter (LES or gastroesophageal sphincter) is present at the junction of
esophagus with the stomach. The upper and the lower esophageal sphincters
normally keep closed to prevent reflux. The esophageal sphincters normally open
only transiently to permit passage of the swallowed food bolus into the
stomach.
The diaphragmatic opening of the esophagus
is formed by special muscles that form sling around the esophagus. The
diaphragmatic crural muscle constitute external sphincter around the distal
esophagus.
C. DEFENCES AGAINST REFLUX DAMAGE
Normally, damage caused by refluxed acid
is avoided by a variety of defense mechanisms that include prompt clearing of
the refluxed acid, neutralization of the acid by salivary and esophageal
bicarbonate secretion and an inherent property of the esophageal lining to defend
against acid, called mucosal defense mechanism
A. BREAKDOWN OF ANTIREFLUX BARRIERS
GERD occurs when there is excessive GER
due to major breakdown of antireflux barriers. The failure of antireflux
barriers occurs due to development of hiatal hernia, incompetence of the
esophageal sphincters and gastric stasis. Hiatal hernia disrupts the
normal anatomy of the gastroesophageal junction. Hiatal hernia leads to
thoracic placement of the abdominal esophagus, obliteration of the angle of His
and the mucosal flap. Moreover, hiatal hernia is associated with widening of
the esophageal hiatus and weakening of the diaphragmatic external lower
esophageal sphincter mechanism. The incidence of sliding hiatal hernia
increases with age.
The failure of LES barrier function occurs
when it is rendered permanently hypotensive or when a normotensive LES relaxes
inappropriately thereby promoting reflux. Permanently hypotensive LES occurs
due to primary or secondary muscle disease of the lower esophageal sphincter.
Inappropriate LES relaxation is transient reflex relaxation of the LES,
mediated by neural reflex. This reflex is similar to belch reflex and has been
called transient LES relaxation (TLESR), in order to distinguish it from
sustained LES hypotension. Elevation in stomach pressure and stasis of food
also predispose to esophago-gastric reflux.
The upper esophageal sphincter guards
against invasion of reflux above the esophagus, into the throat, voice box,
lungs and mouth. Breakdown of the barrier function of the upper esophageal
sphincter leads to Supraesophageal complications of GERD.
B. BREAKDOWN OF DEFENCES AGAINST REFLUX
If excessive reflux occurs, its damaging
effect of acid and pepsin are countered by esophageal mucosal defenses. The
exact nature of the defense mechanisms is not well understood. However,
breakdown of defenses against the invading acid leads to severe mucosal
damage.
Acid and the enzyme, pepsin, secreted by
the stomach are important components of gastric contents that reflux into the
esophagus. Pepsin can only digest esophageal lining when acid is present.
Therefore, acid is the most important damaging agent. However, intestinal
enzymes and bile can backup into the stomach and then reflux into the esophagus
and cause reflux damage. Nonacid reflux causes nonacid GERD that present
special problems in diagnosis and treatment as these cases do not respond to
acid suppression therapy. With the current availability of powerful acid
suppressants, nonacid GERD is emerging as important clinical condition.
5. CLINICAL RISK FACTORS FOR GERD
A. AGE
GERD is a particularly frequent problem in
infants and children and the elderly. Infants and children can not express
heartburn and may present with regurgitation, vomiting and failure to thrive.
B. LIFE STYLE FACTORS
There are many life style factors that
increase the risk of GERD. These include age, weight gain, increased
intragastric pressure, certain diets and smoking. Infants have a high incidence
of gastroesophageal reflux. The incidence of GERD also increases with advancing
age. Recent weight gain is an important precipitating factor in heartburn.
Weight gain, bending and abdominal exercises including jogging, thigh belts and
girdles increase pressure in the stomach and promote reflux. A large meal,
particularly one with a chemical composition that delays gastric emptying or
causes relaxation of the LES also predisposes to reflux. For example, a large
fatty meal may delay gastric emptying and relax LES. Beverages such as colas,
coffee and tea containing high levels of caffeine also relax LES. Smoking is a
potent inhibitor of LES pressure and therefore a very important risk factor for
GER.
C. PREGNANCY
Pregnancy is often associated with GERD.
In the first trimester, hormonal changes that are responsible for morning
sickness can lead to reflux. In the third trimester, increasing intra-abdominal
pressure is responsible for reflux.
D. SYSTEMIC DISEASES
Certain systemic diseases also predispose
to GERD. Coronary artery disease shares many risk factors such as age, obesity
and smoking with GERD. Moreover, many treatments such as coronary vasodilators
reduce LES tone and lead to reflux. Chronic bronchitis and chronic obstructive
lung disease share with GERD smoking as a common risk factor and reduced oxygen
concentration in the blood impairs the normal tone of the LES. Scleroderma and
other connective tissue disorders may involve smooth muscle of the esophagus
and the lower sphincter and predispose to GERD. Moreover, scleroderma involves
the entire esophageal smooth muscle leading to weak and ineffective esophageal
peristaltic contractions that fail to clear the esophagus of the refluxed acid;
therefore, acid stays in the esophagus for longer periods, thus worsening the
esophageal damage. Delayed emptying of stomach due to obstruction to stomach
outlet or poor stomach motility is also an important risk factor for
GERD.
D. SURGICAL PROCEDURES
Certain surgical procedures require
destruction of the lower sphincter for treatment of the underlying disease or
are associated with gastric stasis and may therefore predispose to reflux. For
example, cutting of non-opening lower esophageal for treatment of dysphagia in
patients with achalasia may be complicated by GERD. Abnormal gastric stasis of
food acid either as a complication of gastric surgery or due to other causes
may lead to GERD. Abnormal accumulation of fluid in the abdomen (ascites) or an
abdominal mass may increase intragastric pressure and predispose to reflux.
E. MEDICATIONS
A large variety of commonly used drugs are
also risk factors for GERD. Common among them are drugs that relax smooth
muscles. These include coronary artery dilators that are used for treatment of
coronary artery disease, bronchodilators that are used for treatment of chronic
bronchitis, asthma and chronic obstructive lung disease, and penile
vasodilators that are used for erectile dysfunction. All these smooth muscle
relaxants also relax the lower esophageal sphincter and make it incompetent to
prevent reflux.
Reflux of gastric contents can produce
extensive damage to the esophagus, throat, lungs, ear, nose and mouth depending
upon the extent of the reflux.
A. DAMAGE TO ESOPHAGEAL MUCOSA
The esophageal mucosal lining is very different
from the lining of the stomach. Whereas the lining of the stomach can withstand
acid damage, the esophageal lining is very sensitive to acid damage. Moreover,
the ability of the esophageal mucosa to defend against the acid damage may vary
in different individuals and in the same individual under different
circumstances. This property of the esophageal mucosa to defend against the
acid injury is called mucosal defense.
The biology of esophageal mucosal defense
mechanisms is under investigation. Briefly, it includes changes in penetration
of acid into the depths of the mucosa and changes in the ability of the cells
lining the esophagus to protect them from acid. Certain medications may worsen
esophageal mucosal damage. These medications include ulcerogenic drugs such as
acetylsalicylic acid and non-steroidal anti-inflammatory agents.
Acid damage to the esophageal mucosa is
repaired in different ways depending upon the circumstances. Often the damaged
mucosa is well repaired so that no grossly visible sign of the damage is
apparent. These cases are called non-erosive esophagitis (NERD). These cases
show no signs of damage visible to the naked eye on
endoscopy. However, the mucosal biopsies may show microscopic
changes suggestive of enhanced reparative processes, such as an increase in the
number of basal cells. Dilation of the intercellular spaces, indicating
passages for the invasion by acid has been proposed as the earliest changes of
mucosal damage. Such cases may have symptoms of reflux and heartburn with
normal endoscopy and are given a diagnosis of non-erosive esophagitis (NERD).
Classical cases reflux damage show mucosal
erosions or superficial ulcers. These erosions can vary in size and depth and
may expose and include mucosal blood vessels in the erosions leading to
bleeding. These cases are classified as having erosive esophagitis.
Sometimes ulceration and inflammation
extend deeper in the esophageal wall resulting in deep peptic ulcer of the
esophagus. Healing of the deep inflammation and ulcer leads to scarring and
fibrosis that may occlude the esophageal lumen. This condition is
called peptic stricture.
Repair of the damaged esophageal mucosa
may also occur by a more acid resistant type of columnar epithelium – a
condition called metaplasia. Metaplasia is defined as replacement of one type
of mucosa with another kind. The replacement of damaged esophageal squamous
epithelium by the metaplastic columnar epithelium has been called Barrett’s
esophagus. The metaplastic epithelium is a mosaic of different types of
columnar cells including the so called specialized intestinal metaplastic
epithelium. It has been called specialized because it is different from any
normal epithelium present anywhere in the gut including stomach and intestines.
The development of Barrett’s esophagus occurs painlessly without the patient
being aware that it is happening. Barrett’s esophagus is of special clinical
importance because it may progress to esophageal cancer (see knol on Barrett’s
Esophagus). Deep peptic ulcer of the esophagus and esophageal stricture are
often associated with Barrett’s esophagus.
Acid penetration in the inflamed
esophageal mucosa stimulates mucosal nerves that conduct sensation of pain and
heat thus producing heartburn. The severity of heartburn does not correlate
with the severity of mucosal damage. Severe esophageal damage may exist in the
absence of significant heartburn. In fact the heartburn often abates when
Barrett’s esophagus develops.
B. DAMAGE TO STRUCTURES ABOVE THE
ESOPHAGUS
If acid reflux extends beyond the
esophagus, it produces supra esophageal manifestations.
This occurs when the reflux material is
copious and when the upper esophageal sphincter mechanism is compromised.
Supraesophageal manifestations may include Pharyngitis, laryngitis, sinusitis,
asthma, chronic bronchitis, aspiration pneumonia, pulmonary fibrosis,
sinusitis, otitis and dental erosions.
A. THE WIDE SPECTRUM OF GERD SYMPTOMS
GERD produces a very wide spectrum of
clinical manifestations depending upon the extent and severity of the damage.
Regurgitation is experience of backflow of stomach contents into the esophagus
and the throat. Acid tasting fluid may be experienced in the mouth and the
throat. Sometimes the patient may experience warm fluid climbing up the throat.
Distal esophagus is most often affected by
reflux and in severe cases more proximal parts of the esophagus are also
involved. Esophageal symptoms include: regurgitation, heartburn,
dysphagia, bleeding and chest pain.
Heartburn is pain of burning quality that
is experienced in the region of the heart, namely the retrosternal area or
behind the chest in the midline. Heartburn associated with regurgitation is
characteristic of reflux esophagitis. However, heartburn may be experienced
in some esophageal motility disorders, including
achalasia. Sometimes, pain in coronary artery disease may be
interpreted as heartburn.
Bleeding may be overt in the form of
vomiting of blood or occult internal bleeding presenting as anemia. Bleeding
occurs from mucosal erosions or esophageal ulcer.
Dysphagia may occur due to peptic
stricture or from esophageal adenocarcinoma from Barrett’s esophagus.
Chest pain of associated with GERD
may be confused with angina-like pain or atypical chest pain that
neither resembles typical heartburn nor is exertion related. GERD is the
commonest cause of noncardiac chest pain (see knol on noncardiac chest pain).
When reflux extends above the esophagus to
damage pharynx, voice box, lungs and mouth, symptoms such as hoarseness, throat
irritation, globus sensation, chronic cough, sinus pain, ear ache, dental
erosion and halitosis may be experienced.
It is important to point out that extent
and the severity of reflux damage may not correlate. For example,
reflux damage extending above the esophagus may occur in the absence of severe
lower esophageal damage.
Diagnosis of GERD can be
suspected by its symptoms. The most characteristic symptoms of GERD
are regurgitation and heartburn. Heartburn is most frequently
described as a sub-sternal (under the middle of the chest) burning that occurs
after meals and often worsens when lying down. Patients usually self diagnose
the condition. Physicians can more precisely perform symptom analysis to
diagnose GERD.
A. Therapeutic Trial
The diagnosis of GERD can be substantiated
by the so called therapeutic trial that involves treating patients with
medications to suppress the production of acid by the stomach. If the heartburn
then is diminished to a large extent, the diagnosis of GERD is substantiated.
It is important to keep in mind that 20% of patients may respond to a placebo
(inactive) pill or, indeed, to any treatment. These patients may be suffering
from diseases other than GERD. Therefore, history and response to therapy can
only provide a presumptive diagnosis of GERD related esophagitis. For a
definitive diagnosis, further diagnostic test are needed. In clinical practice,
further investigations are performed if the symptoms persist, there is a long
history of heartburn or warning symptoms such as bleeding, dysphagia and weight
loss are present.
B. Endoscopy
Esophagoscopy involves visualization of the esophageal mucosa through a
flexible tube that is swallowed by the patient and a video of the esophageal
mucosal appearance is made with an optical laser. Esophagoscopy is always
combined with examination of the pharynx, and further extension of the imaging
device into the stomach (gastroscopy) and upper small intestine (duodenoscopy)
and therefore the procedure is called esophago-gastro-duodenoscopy or EGD.
The esophagus of up to 70% of the patients
with symptoms of reflux may appear normal on endoscopy. These patients may have
endoscopically negative esophagitis or nonerosive reflux disease (NERD).
However, endoscopy readily recognizes inflamed esophagus (esophagitis) with
erosions (superficial breaks in the esophageal lining) and is called erosive
reflux disease (ERD). Esophagitis with deep peptic ulcers (deep craters) and
peptic strictures may be seen. Most importantly, endoscopy may
reveal that abnormal columnar mucosa has replaced the normal esophageal mucosa,
a condition called Barrett’s esophagus. The diagnosis of Barrett’s esophagus is
confirmed by biopsy. Barrett’s esophagus may be associated with erosive esophagitis,
deep peptic ulcer, peptic stricture or adenocarcinoma. Finally, endoscopy may
recognize other problems that may be causing GERD-like symptoms. For example,
infectious causes of esophagitis, eosinophilic esophagitis resemble reflux
esophagitis. Gastritis, duodenitis and gastric and duodenal ulcers may cause
lower midline chest pai
C. Biopsies
Biopsies of the esophageal mucosa can be obtained by a biopsy forceps carried
on a flexible wire that can be inserted through an opening channel in the
endoscope. Cutting a small piece of mucosa with biopsy forceps is not painful.
Biopsy tissue can be subjected to microscopic examination. Biopsies may help
establish causes of esophageal inflammation including acid reflux and other
than acid reflux, particularly infections. Moreover, biopsies are the only
means of diagnosing the cellular changes of Barrett's esophagus and carcinoma.
D. Barium X-rays
X-ray of the esophagus (esophagogram) is performed by swallowing radio-opaque
barium (called barium swallow). It is usually combined with x-rays of the whole
upper gastrointestinal tract including the stomach and upper small intestines
(called upper gastrointestinal (UGI) series). X-rays can not identify
esophageal mucosal inflammation unless severe damage is present such as ulcers
and strictures. X-rays often identify hiatal hernias, stomach ulcers or gastric
stasis. Unless it is very severe, finding of gastroesophageal reflux on x-rays
does not distinguish normal GER from GERD.
E. Ear, Nose, Throat and Pulmonary Examination
When GERD affects the throat or larynx and causes symptoms of cough,
hoarseness, or sore throat, patients often first visit an ear, nose, and throat
(ENT) specialist. The ENT specialist frequently finds signs of inflammation of
the throat or larynx... however, distinguishing inflammation due to other
causes including smoking, is often difficult to distinguish from reflux induced
damage. Often acid-suppression is used as a therapeutic trial.
F. Special test for diagnosis of GERD
Special tests for diagnosing GERD are
needed in difficult to diagnose cases
a. Esophageal acid reflux testing
Whether reflux of acid is present and how bad it is when it does occur can be
definitively determined by 24 hour esophageal pH recording. Esophageal pH
monitoring can be performed using a nasally introduced catheter or a pH capsule
(Bravo*) anchored in the lower esophagus. A pH sensor for nasal
placement consists of a thin flexible wire, carrying a pH sensor at its tip
that is passed through the nose and positioned in the
esophagus. Changes in esophageal pH are registered onto a portable
recorder. Episodes of esophageal reflux are recorded as periods of esophageal
pH less than 4 and analyzed.
In order to avoid prolonged nasal
intubation, a small pH sensitive wireless capsule can be implanted in the
distal esophagus. The capsule implantation requires endoscopy and intubation
which are removed after implantation of the capsule. The capsule can transmit
information on esophageal pH to an external receiver for up to 48 hours.
Despite obvious advantages, use of the capsule has some limitations such as
cost, technical problems with capsule attachment and chest pain.
Esophageal pH testing is used only in
difficult to diagnose cases of GERD. For example, it may be used in cases that
fail to respond to acid suppression treatment. Almost 10 to 20
percent of patients may not improve with treatment for GERD. This lack of
response to treatment could be caused by suboptimal treatment or persistent
symptoms that are not related to acid reflux such as changes in esophageal
sensitivity, nonacid reflux or wrong diagnosis of GERD. Finding of abnormal
acid reflux, while the patient is on continued medication, suggests suboptimal
treatment and calls for better compliance, and changes in treatment strategy.
Finding of no abnormal reflux despite continued symptoms, suggest either
increased sensitivity or wrong diagnosis. These latter findings require further
tests to distinguish between the two.
Esophageal pH testing is also often used
to evaluate patients prior to endoscopic or surgical treatment for GERD. These
interventional therapies are effective only in the well documented cases of
acid reflux. Therefore, proper patient selection is necessary to avoid
treatment failures. Only patients with symptoms and well documented acid reflux
should be subjected to interventional therapies. Recent studies suggest that
nonacid reflux may also cause esophageal symptoms. Nonacid reflux may be tested
by impedance studies.
b. Esophageal nonacid reflux testing
Esophageal pH recording does not identify
reflux of nonacid gastroesophageal contents. Nonacid gastroesophageal reflux
can be measured by esophageal impedance recording.
Esophageal pH and impedance studies can be
performed simultaneously using instrumentation that can monitor both these
parameters.
c. Esophageal motility testing
Esophageal motility testing requires placement of an assembly of multiple
sensors that sense pressures from different regions of the esophagus. The
number of sensors used varies in different manometry laboratories. A large
number of sensors may be used to simultaneously record pressure at every
centimeter or three sensors can be used to record pressures 5 cm
apart. Similarly, the pressure sensors may consist of open tip
perfused catheters or solid state pressure sensors. The catheter assembly is
passed through a nostril, down the back of the throat, and into the esophagus.
Pressures in the esophagus and esophageal sphincters between and during
swallows of sips of water are recorded.
Esophageal motility study is not directly
useful in the diagnosis of GERD. However, it may be useful in differential
diagnosis of GERD from esophageal motility disorders such as diffuse esophageal
spasm and achalasia. Esophageal manometry is also useful prior to surgical or
endoscopic treatment for GERD. This may help document the severity of LES or
UES hypotension and efficiency of esophageal peristalsis that may influence the
type of antireflux surgery. Esophageal manometry is also helpful in excluding misdiagnosis
of GERD instead of a motility disorder and association of a motility disorder
with GERD that may compromise the results of antireflux intervention.
d. Esophageal Acid perfusion test
in reflux acid esophagitis, heartburn is thought to be due to the exposure of
esophageal nerve endings in the damaged mucosa to refluxing acid. Healthy
esophageal mucosa does not cause heartburn when exposed to acid. Therefore, the
acid perfusion test (also called Bernstein test) is used to determine if
heartburn is caused by acid reflux. A thin tube is passed through one nostril,
down the back of the throat, and into the middle of the esophagus. A dilute,
hydrochloric acid solution (0.1 normal HCl) or physiologic salt solution is
alternately perfused through the catheter and into the esophagus. The patient
does not know which solution is being perfused. If acid but not salt solution
produces pain, the diagnosis of acid reflux esophagitis is suggested.
e.Esophageal distension test
Esophageal over-distension causes activation
of esophageal nociceptors that elicit chest pain. In the presence of
increased sensitivity of the esophageal nerves, even a small degree of
distension may elicit chest pain. In this test, patient’s experience of pain in
response to balloon distension is recorded. Esophageal distension studies are
useful in establishing increased esophageal sensitivity in patients with
non-erosive esophagitis.
f. Gastric emptying studies
Gastric stasis predisposes to GER. Therefore, assessment of gastric emptying may
provide important information in the pathogenesis and management of a subset of
cases of GER. For gastric emptying studies, the patient eats a meal labeled
with a radioactive substance. A radioactive sensor is placed over the stomach
and the rate of gastric emptying is measured.
When severe delayed gastric emptying is
associated with GERD, a mechanical cause of gastric stasis should be
investigated and treated. Milder cases associated with motility disorders
should be treated with dietary modifications and prokinetic agents. Gastric
emptying studies should be performed prior to surgical antireflux intervention.
This is helpful in assessing postoperative results and to incorporate surgical
techniques to improve gastric emptying.
Some patients with GERD have symptoms of
nausea and vomiting. An evaluation of gastric emptying may be useful in
identifying patients whose symptoms are due to gastric stasis rather than to
GERD.
A. LIFE STYLE CHANGES
Life-style changes could have a very
strong effect on GER. Life style changes include a combination of several
changes in habit, particularly related to eating.
Normal upright posture helps prevent
backflow of stomach acid into the esophagus and gravity also helps return of
any refluxed material back into the stomach. Lying down, as during sleep,
eliminates the beneficial effect of gravity on reflux and the gastric acid may
reflux more frequently, reach higher levels of the esophagus and stay in the
esophagus longer. Prevention of this cycle of events can be accomplished
by elevating the head-end of the bed with blocks (about 4”) placed under the
head of the bed or by placing a wedge in the upper half of the bed. Elevating
only the head does restore the effect of gravity on the esophagus. Elevation of
the upper body at night may be helpful in all patients with GERD, but is
essential for patients who have heartburn, regurgitation, aspiration or other
symptoms of GERD. Lying on the left side also reduces the amount and
frequency of reflux compared with lying on the right side.
Changes in the volume, timing and type of
food intake may be useful in prevention of reflux. Over-distension of the
stomach predisposes to reflux and also promotes reflux by relaxation of the
lower sphincter. Reflux is common after a large meal. A smaller size of meal
and avoiding intake of large quantities of water or fluids with meals may help
avoid reflux. Since a large meal may be particularly harmful before retiring to
bed, a smaller and earlier evening meal may reduce the amount of reflux.
Smaller evening meals may also lower the volume of acid secretion resulting in
overall lower residual gastric volume.
The nature of food may have an effect on
esophageal mucosa, lower esophageal sphincter and gastric motility and thereby
affect symptoms and the occurrence of GERD. Acidic content, osmolality and
irritants in the food may increase the experience of heartburn. Certain acidic
juices, such as citrus juice, tomato juice, carbonated beverages, wines, and
highly osmolar spicy food cause heartburn in some patients with GERD. Peppers
may produce bad heartburn in subjects who are not used to it; however, in
chronic users, peppers may not cause heartburn due to desensitization.
Some foods decrease LES pressure and
others delay gastric emptying and thus promote reflux. These food constituents
and additives include: chocolate, peppermint, alcohol, and caffeinated drinks.
Fatty foods also delay gastric emptying
Smoking has a powerful inhibitory effect
on the pressure in the sphincter and, therefore, promotes reflux. In addition,
patients with GERD may find that other foods aggravate their symptoms. Such
foods should be avoided.
B. MEDICATIONS FOR TREATMENT OF GERD
a. Antacids
Over-the-counter antacids remain a mainstay of self treatment of heartburn.
Antacids neutralize refluxed esophageal and secreted gastric acid so that there
is no acid to reflux. The action of acid is prompt. The problem with antacids
is that they are quickly emptied from the empty stomach and do not produce sustained
acid neutralization. Therefore, antacids donor provide efficient neutralization
night.
Common antacids are aluminum, magnesium,
or calcium salts. Aluminum-containing antacids can cause constipation and
magnesium-containing antacids cause diarrhea. Certain antacid preparation use a
mixture of aluminum and magnesium based compounds to avoid these side
effects. Calcium-based antacids such as calcium carbonate (Tums,
Rolaids) can elevate serum calcium levels and stimulate the hormone gastrin. Release
of gastrin may lead to rebound overproduction of gastric acid. Gastric rebound
may predispose to GER after initial gastric neutralization by calcium
containing antacids. Calcium containing antacids may provide a source of
calcium for patients who require calcium supplementation.
Because of the prompt acid neutralization,
antacids provide immediate relief of heartburn. For long-term
gastric acid neutralization, antacids may be taken approximately one hour after
meals and a second dose of antacid is administered two hours after a meal. Even
so, antacids do not provide sustained neutralization of gastric acid unless
they are administered on an hourly basis or as continuous gastric infusion.
Administration of very large quantities of antacids increase gastric volume and
may lead to nonacid reflux.
Antacids may be combined with a foam
barrier. For example, Gaviscon* is a combination of aluminum hydroxide gel,
magnesium trisilicate and alginate. Alginate tablet disintegrates as it reaches
the stomach and turns into foam that floats on the top of the stomach contents.
The foam is thought to form a physical barrier to the reflux of acid. Moreover,
the antacid bound to the foam neutralizes acid that comes in contact with the
foam. The tablets are taken after meals and on lying down.
b. Histamine-2 (H2) receptor
antagonists
Stomach acid is produced by special acid producing cells called parietal cells
that are located in the stomach wall. Histamine is produced in the
enterochromoffin cells and is released in response to feeding. Histamine
binds with H2receptors on the parietal cells to stimulate acid
secretion. Histamine 2 receptor antagonists bind to the H2 receptors
and block the action of histamine, thereby inhibiting gastric acid secretion.
Unlike antacids, H2 receptor
antagonists act by suppressing secretion of stomach acid. Therefore, H2 blockers
are effective in relieving heartburn symptoms. However, H2 blockers
only partially suppress gastric acid. Because of their weak effect on
suppressing acid secretion, they are not very good for healing erosive
esophagitis associated with GERD. Therefore, H2 receptor
blockers are used for treatment of heartburn in non-erosive esophagitis in
GERD, but not in GERD associated with erosive esophagitis, ulcers and
strictures.
Four different H2 antagonists
have been approved by the FDA for treatment of GERD, including cimetidine
(Tagamet), ranitidine (Zantac), nizatidine (Axid), and famotidine (Pepcid).
Tagamet-HB (100 mg), Zantac-75 (5mg), Axid-AR (75mg) and
PepsidAC (combination of famotidine 10 mg or 20 mg, and calcium carbonate) are
also available over-the-counter (OTC), without the need for a prescription.
Tagamet is available in generic form as cimetidine. The OTC dosages are lower
than those available by prescription. H2 antagonists are best taken 30 minutes
before meals so that its level will peak at meal time when stomach acid
secretion will be at its maximum. H2 antagonists are also
administered at bedtime to suppress nighttime production of acid. These agents
may relieve heartburn but do not heal erosive esophagitis.
c. Proton pump inhibitors
Proton pump inhibitors (PPI) act directly on the parietal cells to block the
proton pump that is responsible for acid secretion. The PPI shut off acid
production more completely and for a longer period of time than H2 receptor
blockers. Because of their very effective acid suppression, PPIs are used as
first line treatment or when H2 antagonists do not relieve
symptoms adequately or when complications of GERD such as erosions, ulcers, or
strictures are present.
Five different PPIs are FDA approved for
the treatment of GERD, including omeprazole (Prilosec), esomeprazole (Nexium),
lansoprazole (Prevacid), rabeprazole (Aciphex), pantoprazole (Protonix).
Omeprazole OTC (20 mg) is approved for over the counter use and is less
expensive than its physician prescribed version.
Timing of PPI administration is very
important for its optimal acid suppressive action. PPIs work best when the
stomach is most actively producing acid, which occurs after meals. Moreover,
PPIs are pro-drugs that require conversion to active agent by acid secretion.
is, Administration of a PPI 30 minute before a meal yields peak levels of PPI
that coincide with active acid secretion. For the same reason, a PPI should not
be combined with H2 receptor blocker.
d. Pro-kinetic drugs
Prokinetic drugs are those that enhance gastrointestinal transit. Currently,
only one prokinetic drug, metoclopramide (Reglan), is approved for GERD. It
increases lower esophageal sphincter pressure and strengthens esophageal
peristaltic contractions. It is thought that the main beneficial effect of
metoclopramide may by enhancing gastric emptying. These drugs are not effective
for treating symptoms of heartburn but may be added to other treatments in case
of suboptimal response. Metoclopramide is not available over the counter. These
drugs are recommended to be taken 30 minutes before meals and again at bedtime.
C. TREATMENT OF GERD WITH ENDOSCOPIC
DEVICES
A variety of endoscopic techniques have
been developed for GERD endotherapy. These devices are designed to change the
anatomic configuration of the gastroesophageal junction and improve function of
the LES. They include devices such as: Entreyx, Gatekeeper, His-Wiz,
SelfStitch, Esophyx, EndoCinch and NDOPlicator. Many of these devices have been
withdrawn from the market because of undesired complications and side effects.
EndoCinch involves mucosal suturing and NDO Plicator produces full thickness
placation. They are still undergoing clinical trials for their
efficacy and safety. So far clinical studies of their usefulness have focused
on uncomplicated and mild cases of GERD.
D. TREATMENT OF GERD WITH SURGERY
Over the years, a variety of operations
have been developed to correct impaired antireflux barriers. These have
included reduction of hiatal hernia (Allison’s repair), Belsey repair and
Nissen fundoplication. Nissen fundoplication has been shown to be effective in
prevention of reflux. Post-operative complications include recurrence of hiatal
hernia and gastroesophageal reflux (20% to 40%). Major complications such as
esophageal obstruction and leak may occur in less than 5% and operative
mortality is around 1%.
10. APPROACH TO MANAGEMENT OF GERD
A. SELF TREATMENT OF HEARTBURN
Most sufferers of simple short duration
heartburn or reflux self treat with life style changes and over-the-counter
medications Life style changes as described above. Over the counter
medications include antacids, H2 receptor blockers and PPI. H2 receptor blockers
and PPI are available over the counter in doses that are smaller than available
for medical prescription.
B. WHY TREAT GERD?
The most important reason for treating
GERD is to relieve symptoms of heartburn. While non-erosive esophagitis (NERD)
may be source of severe heartburn or chest pain, it may not progress to erosive
esophagitis and associated complications even if untreated or partially
treated. Therefore whatever treatment that relieves symptoms is acceptable.
However, erosive esophagitis may lead to complications and should be
aggressively treated to healing and kept healed with effective acid suppressive
therapy. Serious complications of esophageal peptic ulcer are
prevented if the ulcer is kept healed by proper acid suppression. Similarly,
peptic strictures respond to endoscopic esophageal dilation only when effective
acid suppression is provided. Erosive esophagitis associated with Barrett
esophagus also require effective suppression of stomach acid; however, acid
suppression may not prevent either extension of the Barrett’s mucosa or its
progression to cancer (see knol on Barrett’s Esophagus).
C. WHEN TO SEEK MEDICAL HELP?
Medical help should be sought when there
are alarm symptoms such as dysphagia, overt bleeding, anemia, weight loss or
loss of appetite. Medical help should also be sought if there is a long history
of reflux and heartburn. With a history of longstanding heartburn,
it is prudent to seek medical advice even if the symptoms have improved. This
is because development of Barrett’s metaplasia may be associated with a
decrease in symptoms of heartburn. These situations usually call for endoscopic
evaluation of the esophagus. Medical help should also be sought if chest pain
is atypical, exert ional or associated with squeezing in the chest, particularly
if there is history or risk factors for coronary artery disease. In general, if
the symptoms persist despite simple self treatment, medical evaluation should
be done.
D. MEDICAL APPROACH
The physician will obtain a careful
history and perform a physical examination. Coronary artery disease and other
causes of chest pain are excluded. The presence of alarm symptoms such as
bleeding, anemia and dysphagia, weight loss or certain atypical symptoms often
lead to a decision to perform an EGD.
Diagnosis of deep peptic ulcer requires
aggressive PPI therapy; peptic stricture requires treatment with dilation and
aggressive PPI. Esophagitis associated with Barrett’s esophagus is treated like
erosive esophagitis and a surveillance plan to detect early adenocarcinoma is
put in place.
Uncomplicated cases of GERD are separated
from erosive esophagitis. These cases require aggressive PPI therapy to heal
esophagitis that takes 8 to 12 weeks. A repeat EGD to document healing is
usually not necessary. Non-erosive esophagitis and healed erosive
esophagitis cases require long-term acid suppression for symptom control. Most
patients require life long PPI therapy. Patients with NERD could be treated
with H2 receptor blockers if they can produce symptomatic relief. It is important
to ensure that PPI is taken 30-40 min before breakfast, in order to have
optimal acid suppression.
Almost 30% to 40% of these cases may not
improve on PPI. Often these are cases have either normal or minimally abnormal
EGD. The usual causes of poor response are poor compliance, persistence of
nonacid reflux, and non-reflux associated chest pain.
It is this subset of patients in whom 24
hour pH recording, pH plus impedance recording or esophageal motility studies
may be useful. If elevated esophageal acid reflux parameters are present while
on therapy, changes in life style measure, proper administration of PPI or
increase in PPI dose is recommended.
If no acid reflux is identified, symptoms
may be due to nonacid reflux or non-reflux related chest pain. Nonacid reflux
can be diagnosed by impedance studies. Nonacid reflux requires treatment with
endoscopic or laparoscopic fundoplication. If no acid or nonacid reflux is
found, symptoms may be due to esophageal hypersensitivity and may be associated
with anxiety state, panic attacks or depression. This diagnosis calls for special
treatment.
Further
Reading
- Diamant, NE. Pathophysiology of gastroesophageal reflux disease. GI
Motility online (2006) doi:10.1038/gimo21
- Fass, R. M.D. and Dickman, R. Nonerosive reflux disease. GI Motility
online (2006) doi:10.1038/gimo42
- Harding, SM. Gastroesophageal reflux and chronic cough. GI Motility
online (2006) doi:10.1038/gimo77
- Hogan, WJ. Endoscopic therapy for gastroesophageal reflux disease. GI Motility
online (2006) doi:10.1038/gimo55
- Holloway, RH. Esophageal manometry. GI Motility online (2006)
doi:10.1038/gimo30
- Kahrilas, PJ, and Pandolfino, JE. Hiatus hernia. GI Motility
online (2006) doi:10.1038/gimo48
- Lee, R, and Mittal, R. Heartburn and esophageal pain. GI Motility
online (2006) doi:10.1038/gimo75
- Lowe, RC. Medical management of gastroesophageal reflux disease. GI Motility
online (2006) doi:10.1038/gimo54
- Lundell, L. Reflux esophagitis and peptic strictures. GI Motility
online (2006) doi:10.1038/gimo43
- McCormick, SE, and Kozarek RA. Endoscopic evaluation of esophageal
motility disorders. GI Motility online (2006)
doi:10.1038/gimo29
- Minjarez, RC and Jobe, BA. Surgical therapy for gastroesophageal
reflux disease. GI Motility online (2006)
doi:10.1038/gimo56
- Mittal RK, Goyal RK. Sphincter mechanisms at the lower end of the
esophagus. GI Motility online (2006) doi: 10,
1038/gimo 14
- Nurko, SM. and Furuta,GT. Eosinophilic esophagitis. GI
Motility online (2006) doi:10.1038/gimo49
- Orenstein, SR. Oral, pharyngeal, and esophageal motor disorders in
infants and children. GI Motility online (2006) doi:10.1038/gimo38
- Orlando, RC. Esophageal mucosal defense mechanisms. GI Motility
online (2006) doi:10.1038/gimo15
- Postma, GN, and Halum, SL. Laryngeal and pharyngeal complications
of gastroesophageal reflux disease. GI Motility online (2006)
doi:10.1038/gimo46
- Robbins J, Bridges, AD, and aylor. A. Oral, pharyngeal and
esophageal motor function in aging. GI Motility online (2006)
doi:10.1038/gimo39
- Sachin Wani, M.D. and Prateek Sharma. Barrett's adenocarcinoma. GI
Motility online (2006) doi:10.1038/gimo45
- Sengupta, JN. Esophageal sensory physiology. GI Motility online
(2006) doi:10.1038/gimo16
- Shaker R. Reflex interaction of pharynx, esophagus, and airways. GI Motility
online (2006) doi:10.1038/gimo11
- Sontag, SJ. and Harding, SM. Gastroesophageal reflux and asthma. GI
Motility online (2006) doi:10.1038/gimo47
- Spechler, SJ. Barrett's esophagus. GI Motility online (2006)
doi:10.1038/gimo44
- Tutuian, R, and Castell, DO. Gastroesophageal reflux monitoring: pH
and impedance. GI Motility online (2006)
doi:10.1038/gimo31