• Gastroesophageal reflux (GER)
– physiologic process
– gastric contents move retrograde from stomach to
• GER Itself is not a disease and occurs multiple times
each day without producing symptoms or mucosal
• Montreal consensus defines GERD as “a condition
which develops when the reflux of stomach contents
causes troublesome symptoms and/or
An imbalance between
•Defensive factors protecting
A. Antireflux barriers,
B. Esophageal acid
C. Tissue resistance
• Aggressive factors
refluxing from the
acidity, volume, and
A. The antireflux mechanism
includes four important components:
1) lower esophageal sphincter (LES)
2) esophageal peristalsis;
3) crural diaphragm; and
4) stomach (the reservoir).
• Involves the distal 3 to 4 cm of the esophagus and at rest is
• Lies within the hiatus created by the right crus of the
diaphragm and is anchored by the phrenoesophageal
ligaments, which insert at the level of the squamocolumnar
• The proximal portion of the LES is normally 1.5 to 2 cm above
the squamocolumnar junction, whereas the distal part( 2 cm),
lies within the abdominal cavity
• Resting LES pressure ranges from 10 to 30 mm Hg,
• pressure of 5 to 10 mm Hg is necessary to prevent GER
A defective LES is identified by one or more of the following
1. average pressure of less than 6 mm Hg,
2. average overall length of 2 cm or less, and
3. average length exposed to the positive pressure
environment of the abdomen (intra-abdominal length) of 1
cm or less.
2. Esophageal peristalsis
• Clears physiologic reflux and thus reduces contact time
between the esophageal epithelium and gastric fluid.
• Ineffective esophageal motility can result in an abnormal
esophageal exposure to gastric juice even in individuals with a
mechanically effective LES and normal gastric function
3. Crural diaphragm
• Provides an extrinsic component to the gastro-esophageal
• It is particularly important as a protection mechanism against
reflux induced by sudden increases in intraabdominal
• This mechanism is disrupted
by the presence of a hiatal hernia where
the intrinsic LES has “migrated” proximal
to the diaphragmatic pinch.
Impaired function of the stomach such as abnormal gastric
emptying may contribute to GERD by increasing intragastric
pressure, distension, and LES unrolling.
This may occur in patients with a
• large hiatal hernia, in which the herniated stomach in the
chest does not empty appropriately,
• gastric outlet obstruction either from malignancy or peptic
• diabetic gastroparesis.
Mechanisms of Reflux
• Reflux usually occurs via 4 mechanisms:
– Low LES pressure,
– Swallow-associated LES relaxation
– Straining during periods of low LES pressure
1. Transient Lower Esophageal
• The most frequent mechanism for reflux in patients
with healthy sphincter pressures
– Independent of swallowing
– Not accompanied by esophageal peristalsis
– Persist longer (>10 seconds) than swallow-induced lesrs
– Accompanied by inhibition of the crural diaphragm
• tLESRs account for nearly all reflux episodes in healthy
subjects and 50% to 80% of episodes in GERD patients
2. Hypotensive LES Pressure
• by either strain-induced or free reflux.
• Strain-induced reflux occurs when a relatively hypotensive
LES is overcome by an abrupt increase in intra-abdominal
pressure from coughing, straining, or bending over.
• Free reflux is characterized by a fall in intraesophageal pH
without an identifiable change in intragastric pressure, usually
occurring when LES pressure is less than 5 mm Hg
• usually observed in patients with end-stage scleroderma or
after myotomy for achalasia
3. Swallow-Induced Lower Esophageal
• 5% to 10% of reflux episodes occur during swallow induced
• more common with a hiatal hernia.
• due to the lower compliance of the EGJ in hernia patients,
permitting it to open at pressures equal to or lower than
intragastric pressure, thereby allowing reflux
• The etiology of a hiatal hernia remains unclear.
• Familial clustering of GERD suggests the possibilities of an
inherited smooth muscle disorder.
• Animal studies propose that reflux itself causes esophageal
shortening, promoting the development of a hiatal hernia.
• Other studies find an association with obesity and heavy
lifting, raising the possibilities that over time, chronic intra-
abdominal stressors may weaken the esophageal hiatus,
causing the development of a hiatal hernia.
The Acid Pocket
• Gastric pH is usually
around 2 in the fasting state.
• During meals, and for approximately 90 minutes thereafter,
the pH reelevated owing to the buffering effects of the food.
• Herein lies a paradox because most episodes of acid reflux
occur immediately after a meal.
• This paradox is explained by the identification of a zone in the
gastric cardia that remains unbuffered, now referred to as the
• This pocket is postulated to be the source of acidic refluxate
and has a pH considerably lower than the distal esophagus
and remainder of the stomach after a meal.
• In GERD patients with hiatal hernia, the acid pocket is further
enlarged because of the proximal migration of the LES.
• when the acid pocket is located about the diaphragm,
especially in a hiatal hernia, more than 70% of the tLESRs
were accompanied by acid reflux.
• In contrast, less than 20% of tLESRs were accompanied by acid
reflux when the acid pocket was below the diaphragm
B. Esophageal Acid Clearance
• second tier of protection against reflux damage is esophageal
• This phenomenon involves 2 related but separate processes:
volume or bolus clearance, which is the actual removal of the
reflux material from the esophagus,
• acid clearance, which is the restoration of normal esophageal
pH following acid exposure through titration with base from
saliva and esophageal gland secretions.
• Gravity contributes to bolus clearance when reflux occurs in
the upright position. At night when supine, this mechanism is
not operative unless the head of the bed is elevated.
• This important lifestyle change markedly improves acid
clearance time and is most beneficial in patients with
aperistalsis (e.g., with scleroderma).
Salivary and Esophageal Gland
• Saliva is the second essential factor required for normal
esophageal acid clearance. The stimulus for salivation appears
to be the presence of acid in the proximal esophagus (20 cm
• Decreased salivation during sleep is the reason that nocturnal
reflux is associated with markedly prolonged acid clearance
• Xerostomia is associated with prolonged esophageal acid
exposure and esophagitis.
• Cigarette smoking promotes GER. Originally attributed to
nicotine’s effect on lowering LES pressure, cigarette smokers
also have hyposalivation, leading to prolonged esophageal
acid clearance time
• This is due to a third tier for esophageal defense.
• Conceptually, tissue resistance can be subdivided into
• pre-epithelial, poorly developed. There is neither a well-defined mucous
layer nor buffering capacity by the surface cells to secrete bicarbonate ions
into the unstirred water layer.
• Epithelial -consist of structural and functional components. Structural
components include the cell membranes and intercellular junctional
complexes of the esophageal mucosa. This structure is a 25- to 30-cell-
thick layer of nonkeratinized squamous epithelium.
• Postepithelial factors, provided by the esophageal blood supply.
Blood flow delivers oxygen, nutrients, and bicarbonate and removes H+
Medical Conditions Associated
withGastroesophageal Reflux Disease
The role of H. pylori infection in the
pathogenesis of GERD:
•There is evidence that H. pylori infection has pathogenic role in
•Virulent strain (Cag A positive) has inverse relationship.
•Depends on anatomical distribution of gastritis
– In Asia, corpus-predominant gastritis is common, and
eradication therapy in these patients may increase the risk
of developing GERD.
– Hp antrum-predominant gastritis has been shown to be
associated with hypergastrinemia and gastric
Typical GERD symptoms-
• Heartburn (ascending retrosternal burning)
• Dysphagia ( 30%)– It can be divided into an
oropharyngeal etiology, which is characterized by difficulty
transferring food out of the mouth into the esophagus,
esophageal etiology, which is characterized by the sensation
of food sticking in the lower chest.
• Water burshing
• precipitated by meals,
• occurring at night while supine,
• responsive to antacid medication,
• or accompanied by other symptoms such as dysphagia
and/or regurgitation - should trigger an evaluation for an
Nocturnal GERD can lead to interruptions in sleep, leading to
high rates of absenteeism from work and a reduced quality of
Laryngeal symptoms of reflux
• globus sensation,
• throat clearing,
• Postnasal drip
• Laryngeal and tracheal stenosis
-shortness of breath
-pulmonary disease like
Tests for Gastroesophageal Reflux
• GERD Questionnaires (RDQ, GERD Q)
• PPI test
• Barium swallow
• pH monitoring (catheter based or wireless)
• Intraluminal impedance-pH monitoring
• Early satiety
• GI bleeding
• Unexplained Weight
• Iron deficiency
Empirical Trial of Acid Suppression
• High PPI dose (e.g., omeprazole 40 to 80 mg/day), usually
given for at least 2 weeks, and a positive response was
defined as at least 50% improvement in heartburn.
• Using this approach, the PPI empirical trial has a sensitivity of
68% to 83% but poor specificity for determining the presence
• More than 50% of patients who have typical GERD symptoms
have normal endoscopic examinations.
• Endoscopy are considered to be performed in patients with
– Alarm symptoms (e.g. dysphagia, weight loss, bleeding,
abdominal mass, age >40 years)
– Diagnostic problems (e.g. atypical symptoms)
– No response to empirical treatment in patient with
• Mild changes of GERD that may be visible to the endoscopist
include mucosal erythema, edema, hyper- vascularity,
friability, and blurring of the SCJ.
• The best validated and most widely used classification system
for reflux esophagitis now is the Los Angeles classification.
• In this system, a mucosal break is defined as, “an area of
slough or erythema with a discrete line of demarcation from
the adjacent, more normal-looking mucosa”.
• Los Angeles classification.
• (a) Grade A is defined as mucosal breaks confined to the mucosal fold, each no longer than 5 mm.
• (b) Grade B corresponds to at least one mucosal break longer than 5 mm confined to the mucosal fold but
not continuous between two folds.
• (c) Grade C is characterized by mucosal breaks that are continuous between the tops of mucosal folds but
• (d) Finally, grade D is represented by extensive mucosal breaks engaging at least 75% of the esophageal
It is used to
• evaluate the entire anatomy of esophagus,
• document the presence and size of a hiatal hernia,
• stricture severity and location,
• diverticula, esophageal emptying, and
• the presence of gastroesophageal reflux, both spontaneously
and induced by provocative maneuvers
• Esophageal motility can be assessed - to some extent
• Most accurate method to assess the coordination and
pressure of the lower esophageal sphincter (LES) and the
Findings in GERD- a defective LES or impaired esophageal
• Important component in the preoperative workup of
Excludes achalasia that may be occasionally misdiagnosed as
• Characterizes the esophageal motility, and this information
will be used to determine the surgical approach (Nissen or
• Enables measurement of the precise location of the LES for
accurate pH probe placement.
Esophageal Reflux Testing
• Ambulatory intraesophageal pH monitoring is still
the standard for establishing pathologic acid reflux.
• Catheter based
The conventional catheter-based pH monitoring system
principally consists of a flexible catheter with one or more pH
sensors and a data logger.
• Catheter- free : wireless pH capsule
• Improved patient comfort
• less effect on reflux-provoking activities
• fixed placement of the pH electrode (5 cm above the SCJ),
• Patients are encouraged to eat normally and engage in regular
daily activities, with monitoring carried out for 18 to 24 hours.
• Reflux episodes are defined by a pH drop of less than 4
• The percentage of total time pH is less than 4 is the most
reproducible measurement for GERD ( Acid exposure time ),
with reported upper limits of normal ranging from 4% to
Tracings from 48-hour esophageal pH . It is a 48-hour pH capsule
study in a patient with GERD. Meals/drinksare shown by the
yellow lines, supine periods are shown in blue. The orange
bars represent symptoms that were associated with acid
MII-pH (MULTICHANNEL INTRALUMINAL
• Impedance testing measures the resistance (or impedance) to
flow of a tiny current across pairs of metal electrodes
implanted on a thin catheter placed transnasally in the
• Able to detect, localize, and classify reflux events as
• weakly acid, or
• The future standard for reflux detection and
monitoring, especially in patients with persistent
typical and/or atypical symptoms despite PPI
• Depends to a great extent on whether the patient has erosive
or nonerosive disease.
• Controversy as to whether GERD exists as a spectrum of
disease severity or
• as a categorical disease in 3 distinct groups: erosive,
nonerosive, and Barrett’s esophagus.
• in follow-ups ranging from 6 months to longer than 22 years,
less than 25% of patients with nonerosive disease evolved
over time to having erosive esophagitis,
• Endoscopy-negative GERD patients are more likely to be female,
younger, thin, and without hiatal hernia, and they have a higher
prevalence of functional GI disorders.
• First patients with excessive acid reflux , usually respond to PPI
• Second are the patients with normal acid reflux parameters but a
good correlation between their symptoms and acid reflux episodes.
This group represents 30% to 50% of nonerosive GERD patients
and, based on recent Rome IV criteria, is classified as “reflux
• The third group is characterized by normal acid exposure times and
poor symptom correlation. This group is classified as “functional
TREATMENT OF GERD
• MEDICAL – includes both lifestyle modifications and
• Foods –
• Acidic liquid such as cola, tea, citrus products such as
orange, grapefruit, and tomato juice are direct esophageal
irritants and will exacerbate symptoms in the GERD
• Coffee and chocolate can decrease LES pressure and may
• A high-fat meal will increase reflux frequency in both
normals and patients with GERD. Fat may increase the risk
of reflux by delaying gastric emptying.
• Eating slowly will reduce reflux as will meals with smaller
• male, older, and overweight and are more
likely to have hiatal hernias
• The clinical course of these patients is more
predictable and associated with complications
• High relapse after discontinuation of PPI
• Body weight:
• A BMI greater than 30 is associated with almost three
times higher risk of frequent reflux symptoms.
• Weight gain has been associated with an increased risk of
symptoms of GERD and weight loss associated with a
decrease in risk.
• Sleep and body position
• Patients with nighttime GERD should begin the sleeping
period with the left side down. - Decrease in transient
lower esophageal sphincter relaxations (TLESRs) on the left
side as compared to the right.
• Refrain from eating within 2 to 3 hours of going to sleep -
As reflux is more frequent in the first half of the sleep
• Alcohol is a smooth muscle relaxant and reduces lower
esophageal sphincter pressure (LESP). Should be used
• May increase esophageal sensitivity to acid by impairing
intracellular regulation of pH.
• Smoking cessation in individuals with GERD has been
shown to reduce the number of upright reflux episodes.
• Antisecretory therapy is still the choice for medical therapy
• Antacids are widely used as first-line treatment for the
heartburn symptoms of GERD
• mucosal protective agent
• Little or no place in normal modern therapy of GERD
H2 RECEPTOR ANTAGONISTS
• antisecretory capabilities are best at night, with duration of
acid inhibition longer when the drug is taken in the evening or
• patients, particularly those with infrequent or mild symptoms
can be managed long-term on as- needed or daily H2RAs.
• Esophagitis healing rates with H2RAs rarely exceeded 60%
after up to 12 weeks.
• grades I and II esophagitis heal in 60% to 90% of patients,
• grades III and IV heal in only 30% to 50% despite high-dose
Proton Pump Inhibitor
• Superior efficacy compared with H2ras on the basis of their
ability to maintain an intragastric Ph > 4 from 10 to 14 hours
daily compared with Approximately 6 to 8 hours daily with the
• Some patients need an increase in PPI dose because of
incomplete symptom relief, extraesophageal symptoms, or
• Healing of even severe ulcerative esophagitis after 8 weeks in
more than 80% of patients taking PPIs, compared with 51% on
H2RAs and 28% receiving placebo.
• Recent approaches to enhance acid suppression with PPIs
include immediate-release omeprazole and dexlansoprazole
• Dexlansoprazole MR is the R-enantiomer of lansoprazole, with
2 distinct drug release periods (90 minutes and 4 to 5 hours
• In a recent placebo-controlled study among 178 patients
receiving twice-daily PPIs, stepping down to once-daily
dexlansoprazole 30 mg, maintained excellent symptom relief
over 6 weeks in 88% of patients.
• Alginic acid derivatives, or alginates, treat GERD via a
unique mechanism by creating a mechanical barrier that
displaces the postprandial acid pocket.
• In the presence of gastric acid, they precipitate into a gel
and form a raft that localizes to the acid pocket in the
• showing fluorescein-labeled alginate on the luminal surface of the
biopsy mucosa after 1 hour of washing in a neutral solution
•Inhibition of pepsin and bile acids. Alginate can remove both
pepsin and bile acids from gastric refluxate.
•Alginates play a major role in the topical protection of the
vulnerable and sensitive esophageal mucosa, reducing the
risk of inflammation from gastric refluxate,
• Although prokinetics may theoretically alleviate the
pathophysiology of GERD by increasing gastric and esophageal
emptying, the evidence behind their clinical efficacy as add-
on therapy over PPI is lacking.
• Combination therapy did not have better efficacy than PPI
alone for symptom control or endoscopic response, and the
combination therapy was associated with worse adverse
• subset of patients with GERD who have delayed gastric
emptying may benefit from the addition of prokinetics
Transient Lower Esophageal Sphincter
• only medication available that decreases
• tLESRs is baclofen, a GABAB agonist used for many years to
• Baclofen (5 to 20 mg 3 times daily) significantly reduces
tLESRs, decreases both acid and duodenal reflux, and
improves symptoms in GERD patients treated for 4 weeks to
ANTI REFLUX SURGERY
Primary Indications for Antireflux Surgery
(1) healthy patients with typical or atypical GERD symptoms
well controlled on PPIs, desiring alternative therapy because
of drug expense, poor medication compliance, or fear of
possible long-term side effects;
(2) patients with volume regurgitation and aspiration symptoms
not controlled on PPIs
(3) GERD complications such as peptic stricture, Barrett
esophagus, or vocal cord injury
• Antireflux surgery reduces acid and nonacid GER by
– increasing basal LES pressure,
– decreasing tLESRs,
– inhibiting complete LES relaxation
Choice of surgery
Factors influencing : -
• degree of esophageal shortening
• disturbances of esophageal motility
• prior operations and
• local expertise with laparoscopic techniques
• Early uncomplicated disease :
– Trans-abdominal Nissen (laparoscopic)
fundoplication. superior operation with better
long-term durability, but it causes more
postoperative dysphagia and gas bloat symptoms.
• Decreased motility :
– Although surgery cannot directly influence esophageal
motility in patients with GERD, Nissen fundoplication can
lead to improvement in esophageal contraction amplitude.
• Normal length but decreased motility :
– Complete fundoplication is discouraged. Toupet or
Hill could be performed
• Shortened esophagus :
– Collis (esophageal lengthening) gastroplasty combined
with an intra-abdominal or intrathoracic fundoplication
• Gas bloat syndrome
• 5-10% failure
Novel Endoscopic/Surgical Therapies
• The newest approach is the transoral incisionless
fundoplication which recreates at 200- to 270-degree value
using polypropylene fasteners placed endoscopically.
• over time the fasteners tend to dislodge, with a systematic
review reporting GERD symptom recurrence in 60% of
patients with a similar rate back on PPIs.
• Magnetic sphincter, which is a necklace of titanium beads
with magnetic cores placed around the cardia, with minimal
dissection of the hiatus.
• Use of electrical stimulation to the LES to improve
LES pressure without interfering with LES relaxation
Complications of GERD
• The most common fatal causes are hemorrhagic esophagitis,
aspiration pneumonia, ulcer perforation, and rupture with
• Peptic Esophageal Strictures
– 7% to 23% of patients with untreated reflux esophagitis.
– Peptic strictures are smooth-walled, tapered, circumferential
narrowings in the lower esophagus, usually less than 1 cm long but
occasionally extend to 8 cm
– Dysphagia to solids , mild weight loss
• Barrett’s Esophagus