GASTROESOPHAGEAL

REFLUX DISEASE
• GERD can be defined as symptoms or complications resulting from refluxed
stomach contents into the esophagus or beyond, into the oral cavity
(including the larynx )or lung.
• Often chronic and relapsing
• Gastroesophageal reflux disease (GERD) occurs when refluxed stomach
contents lead to troublesome symptoms and/or complications.
• Gastroesophageal reflux disease can be further classified as either
symptom-based or tissue-injury based depending on how the patient
presents.
• The absence of tissue injury or erosions is commonly termed nonerosive
reflux disease(NERD).
• Symptom- based GERD may exist with or without esophageal injury and
most commonly presents as heartburn, regurgitation, or dysphagia.Less
commonly, odynophagia or hypersalivation may occur.

Tissue injury- based GERD may exist with or without symptoms.The
spectrum of injury includes esophagitis,Barett’s esophagus, strictures
and esophageal adenocarcinoma.

Complications of long term reflux may include the development of
strictures, Barrett’s esophagus, or possibly adenocarcinoma of the
esophagus.
 EPIDEMIOLOGY

• GERD occurs in people of all ages but most common in those older
than age 40 years.
• Except for NERD and pregnancy, no much difference in incidence
between men and women.
• GERD is an important factor in the development of Barrett's
esophagus and esophageal adenocarcinoma, which are both more
common in men.
• Adenocarcinoma of the esophagus is five-fold more common in those
with chronic GERD symptoms than those who do not have GERD.
 LOWER ESOPHAGEAL SPHINCTER

LES is a specialised thickening of the smooth muscle lining of the distal esophagus with an elevated basal
resting pressure.The sphincter is normally in a tonic contracted state.
• Ant reflux barriers prevent reflux of gastric contents into the esophagus, and
their dysfunction leads to gastroesophageal reflux disease and or dysphagia.

• The ant reflux barriers include two sphincters, namely, the lower esophageal
sphincter (LES) and the diaphragmatic sphincter, and the unique anatomic
configuration at the gastroesophageal junction.

• The two sphincters maintain tonic closure and augmented reflex closure of the
sphincter mechanism.

• They both relax upon swallowing but can also relax without a swallow, as a part
of the reflex called transient LES relaxation (TLESR).

• The LES is composed of smooth muscles, and it maintains tonic contraction

owing to myogenic as well as neurogenic factors. It relaxes due to vagally
mediated inhibition involving nitric oxide as a neurotransmitter.
• The diaphragmatic sphincter is composed of striated muscles that also
exhibit tone and contracts due to the excitatory nerves.

• It relaxes with swallowing and TLESR.

• The loss of inhibitory mechanisms leads to esophageal achalasia, and

increased frequency of TLESR is associated with gastroesophageal reflux
disease.
 PATHOPHYSIOLOGY
• The key factor in the development of GERD is the abdominal reflux
of gastric contents from the stomach into the esophagus, oral
cavity, and/or the lung.

• In some cases, gastroesophageal reflux is associated with

defective LES pressure or function.

• Problems with other normal mucosal defence mechanisms, such

as abnormal esophageal anatomy, improper esophageal clearance
of gastric fluids, reduced mucosal resistance to acid, delayed or
ineffective gastric emptying, inadequate production of epidermal
growth factor, and reduced salivary buffering of acid, may also
contribute to the development of GERD.
• Substances that may promote esophageal damage on reflux into
the esophagus include gastric acid, pepsin, bile acids and
pancreatic enzymes.

• Thus the composition and volume of the refluxate, as well as

duration of exposure, are important aggressive factors in
determining the consequences of gastroesophageal reflux.

• The acid pocket is thought to be an area of unbuffered acid in the

proximal stomach that accumulates after a meal and may contribute
to GERD symptoms post prandially.
 1)Decreased Lower esophageal sphincter
pressure
Primary barrier to gastro esophageal reflux is the Lower
esophageal sphincter.

LES normally works in conjunction with the diaphragm.

If barrier disrupted, acid goes from stomach to esophagus.

May be due to
Spontaneous transient LES relaxations
Transient increase in intra abdominal pressure
An atonic LES
2)Disruption of Anatomic factors

• Associated with hiatal hernia( when a portion of the stomach

protrudes through the diaphragm into the chest).

• The size of the hiatal hernia is proportional to the frequency of

LES relaxations.

• Hypotensive LES pressures and large hiatal hernias-more

chance of GERD following abrupt increase in intra abdominal
pressure.
3)Esophageal clearance
• The GI acid produced spends too much time in contact with the
esophageal mucosa.

• Contact time is dependent on the rate at which esphagus clears

the material as well as the frequency of reflux.

• Normally swallowing contributes to esophageal clearance by

increasing salivary flow.

• Saliva decreases with increasing age, so more often seen with

elderly.
 4)Mucosal resistance
• The mucus secreted by the mucus secreting glands involves in
the protection of esophagus.

• The bicarbonate moving from the blood to the lumen can

neutralize acidic refluxate in the esophagus.

• On repeated exposure to the refluxate or due to some defect in

normal mucosal defences hydrogen ions diffuse into the mucosa,
leading to cellular acidification and necrosis leading to
esophagitis..
 5) Delayed Gastric emptying/Increased Intra
•
abdominal pressure
Delayed gastric emptying can contribute to gastroesophageal
reflux.

• An increase in gastric volume may increase both the frequency

of reflux and the amount of gastric fluid available to be refluxed.

• Smoking and high fat meals increase gastric volume and

decrease gastric emptying.

• Obesity is considered an independent risk factor for GERD due

to increased intra-abdominal pressure.
 Pathogenesis
• Amount of esophageal damage is seen dependent on
- Composition of refluxed material
- pH and volume of refluxed material
- Length of contact time
- Natural sensitivity of esophageal mucosa
- Rate of gastric emptying

If the pH of the refluxate is less than 2,esophagitis may develop secondary
to protein denaturation.
In addition, pepsinogen is activated to pepsin at this pH and may also
cause esophagitis.
The combination of acid, pepsin and/or bile is a potent refluxate in
producing esophageal damage.
Complications Note:
The use of NSAIDs or aspirin is an
additional risk factor that may contribute
to development or worsening of GERD
complications.
• Esophagitis
• Esophageal strictures
• Barrett’s esophagus
• Esophageal adenocarcinoma
• Haemorrhage and anaemia
• Perforation
• Precipitation of Asthma attack
Erosive esophagitis

• Erosive esophagitis is a condition in which areas of the

esophageal lining are inflamed and ulcerated.The most
common cause of erosive esophagitis is chronic acid
reflux.
• Responsible for 40-60% of GERD symptoms
• Severity of symptoms often fail to match severity of
erosive esophagitis.
Esophageal stricture

• A benign esophageal stricture, or peptic stricture, is a

narrowing or tightening of the esophagus that causes
swallowing difficulties.
• May need dilation
• Common in the distal esphagus and are generally 1-2
cm in length.
Barrett’s esophagus

• Replacement of squamous epithelial lining of the esophagus by specialised

columnar type epithelium- Columnar metaplasia
• Associated with the development of Adenocarcinoma.
• Have a greater chance( 30%) of developing esophageal strictures.
• Acid damages lining of esophagus and causes chronic esophagitis.
• Damaged area heals in a metaplastic process( change in form) and
abnormal columnar cells replace squamous cells.
• This specialised intestinal metaplasia can progress to dysplasia( the
enlargement of an organ or tissue by the proliferation of cells of an
abnormal type, as an early stage in the development of cancer) and
adenocarcinoma
 Asthma
• GERD can lead to the reflux of fluid into the lungs;this can result
in choking, coughing or even pneumonia.In some patients reflux
may worsen asthma symptoms.Treating GERD may help
improve asthma symptoms in these people.GERD can be
worsened by asthma and by some of the medicines that are
used to treat asthma.
CLINICAL MANIFESTATION
• TYPICAL SYMPTOMS

Heartburn-retrosternal burning discomfort

Regurgitation-effortless return of gastric contents into the
pharynx without nausea, retching or abdominal
contractions.
Water brash-hyper salivation
Belching
ATYPICAL SYMPTOMS
In some cases, these extra esophageal symptoms may be the
only symptoms present, making it more difficult to recognise
GERD as the cause, especially when endoscopic studies are
normal.
Non allergic asthma
Hoarseness
Pharyngitis
Chest pain
Dental erosions
Cough
ALARM SIGNS & SYMPTOMS
• These symptoms may be indicative of complications of
GERD such as Barrett’s esophagus, esophageal
strictures, or esophageal cancer.
• Dysphagia(difficulty swallowing)
• Early satiety
• Odynophagia
• Vomiting
• Choking
• Continual pain
• GI bleeding and unexplained weight loss
Symptom-based GERD (with or without esophageal tissue injury)

• Typically presents with heartburn, usually described as a substernal

sensation of warmth or burning rising up from the abdomen that may
radiate to the neck.
• It may be waxing and waning in character and aggravated by activities
that worsen reflux (eg, recumbent position,bending-over, eating a high-
fat meal).
• Other symptoms are water brash (hypersalivation), belching, and
regurgitation.
• Alarm symptoms that may indicate complications include dysphagia,
odynophagia, bleeding, and weight loss.
Tissue injury–based GERD (with or without esophageal symptoms) may
present with esophagitis, esophageal strictures, Barrett esophagus, or
esophageal carcinoma.
• Alarm symptoms may also be present.
• Extra esophageal GERD symptoms may include chronic cough,
laryngitis, asthma, and dental enamel erosion.
 DIAGNOSIS
• Clinical history is sufficient to diagnose GERD in patients with typical
symptoms.
• Perform diagnostic tests in patients who do not respond to therapy or who
present with alarm symptoms. Endoscopy is preferred for assessing mucosal
injury and identifying Barrett esophagus and other complications.
• Ambulatory pH monitoring, esophageal manometry, combined impedance–pH
monitoring, high-resolution esophageal pressure topography (HREPT), and an
empiric trial of a proton pump inhibitor may be useful in some situations.
Antacids and Antacid-Alginic Acid
Products

• Antacids provide immediate symptomatic relief for mild GERD

and are often used concurrently with acid suppression therapies.
Patients who require frequent use for chronic symptoms should
receive prescription-strength acid suppression therapy instead.
• • An antacid with alginic acid (Gaviscon) is not a potent acid-
neutralizing agent and does not enhance LES pressure, but it
does form a viscous solution that floats on the surface of gastric
contents. This serves as a protective barrier for the esophagus
against reflux of gastric contents and reduces frequency of reflux
• Antacids have a short duration, which necessitates frequent
administration throughout the day to provide continuous acid
neutralization. Taking antacids after meals can increase duration
from approximately 1 to 3 hours; however, nighttime acid
suppression cannot be maintained with bedtime doses.
Proton Pump Inhibitors

• PPIs (dexlansoprazole, esomeprazole,

lansoprazole, omeprazole, pantoprazole,and
rabeprazole) block gastric acid secretion by
inhibiting hydrogen potassium adenosine
triphosphatase in gastric parietal cells, resulting in
profound and long-lasting antisecretory effects.
• Adverse effects include headache, dizziness,
somnolence, diarrhea, constipation, and nausea.
Potential long-term adverse effects include enteric
infections, vitamin B12 deficiency, hypomagnesemia,
and bone fractures. PPIs can decrease the
absorption of drugs such as ketoconazole and
itraconazole that require an acidic environment
for absorption. Inhibition of cytochrome P450 2C19
(CYP2C19) by PPIs (especially omeprazole) may
decrease effectiveness of clopidogrel. Other drug
interactions with PPIs also exist
• PPIs degrade in acidic environments and are therefore
formulated in delayed-release capsules or tablets.
Dexlansoprazole, esomeprazole, lansoprazole, and
omeprazole contain enteric-coated (pH-sensitive) granules in
capsules. For patients unable to
swallow the capsules, the contents can be mixed in applesauce
or orange juice. In patients with nasogastric tubes, the contents
can be mixed in 8.4% sodium bicarbonate solution.
Esomeprazole granules can be dispersed in water.
Esomeprazole,omeprazole, and pantoprazole are also available
in a delayed-release oral suspension
powder packet, and lansoprazole is available as a delayed-
release, orally-disintegrating tablet. Patients taking pantoprazole
delayed-release capsule, with the first release occurring 1 to
2 hours after the dose,and the second release occurring 4 to
5 hours after the dose.
• Lansoprazole, esomeprazole, and pantoprazole are
available in IV formulations for patients who cannot take oral
medications, but they are not more effective than oral
preparations and are significantly more expensive.
• Patients should take oral PPIs in the morning 15 to 30
minutes before breakfast or their largest meal of the day to
maximize efficacy, because these agents inhibit only actively
secreting proton pumps. Dexlansoprazole can be taken
without regard to meals. If dosed twice daily, the second
dose should be taken approximately 10 to12 hours after the
 Histamine 2–Receptor Antagonists
• The histamine 2–receptor antagonists (H2RAs) cimetidine,
ranitidine, famotidine,and nizatidine in divided doses are
effective for treating mild to moderate GERD.
• Low-dose nonprescription H2RAs or standard doses given
twice daily may be beneficialfor symptomatic relief of mild
GERD. Patients not responding to standard doses may be
hypersecretors of gastric acid and require higher doses.
• The efficacy of H2RAs for GERD treatment is highly
variable and frequently lower than desired. Prolonged
courses are frequently required.
The most common adverse effects include
headache, somnolence, fatigue, dizziness,and
either constipation or diarrhea. Cimetidine may
inhibit the metabolism of theophylline, warfarin,
phenytoin, nifedipine, and propranolol, among other
drugs.
• Because all H2RAs are equally efficacious,
 Promotility Agents

• Promotility agents may be useful adjuncts to acid

suppression therapy in patients with a known motility
defect (eg, LES incompetence, decreased esophageal
clearance,delayed gastric emptying). However, these
agents are not as effective as acid suppression therapy
and have undesirable side effects.
• Metoclopramide, a dopamine antagonist, increases LES
pressure in a dose-related manner and accelerates gastric
• Common adverse reactions include somnolence, nervousness,
fatigue, dizziness,weakness, depression, diarrhea, and rash.
• Bethanechol has limited value because of side effects (eg,
urinary retention, abdominal discomfort, nausea, flushing).
 Mucosal Protectants

• Sucralfate is a nonabsorbable aluminum salt of sucrose

octasulfate. It has limited value for treatment of GERD but may
be useful for management of radiation esophagitis and bile or
nonacid reflux GERD.
Maintenance Therapy
• Many patients with GERD relapse after medication is withdrawn, so
maintenance treatment may be required. Consider long-term
therapy to prevent complications and worsening of esophageal
function in patients who have symptomatic relapse after
discontinuation of therapy or dosage reduction, including patients
with Barrett esophagus, strictures, or esophagitis.
• Most patients require standard doses to prevent relapses. H2RAs
may be effective maintenance therapy in patients with mild disease.
PPIs are the drugs of choice for maintenance treatment of moderate
to severe esophagitis or symptoms. Usual once-daily doses are
omeprazole 20 mg, lansoprazole 30 mg, rabeprazole 20 mg, or
esomeprazole 20 mg. Low doses of a PPI or alternate-day regimens
 EVALUATION OF THERAPEUTIC
OUTCOMES

• Monitor frequency and severity of GERD symptoms, and

educate patients on symptoms that suggest presence of
complications requiring immediate medical
attention,such as dysphagia or odynophagia. Evaluate
patients with persistent symptoms for presence of
strictures or other complications.
• Monitor patients for adverse drug effects and the