GASTRO-ESOPHAGEAL

REFLUX DISEASES
(G E R D)
By:

PROF. DR Dr I DEWA NYOMAN WIBAWA SpPD-KGEH

Gastroenterology-hepatology Div.,
Dept.of Internal Med./Sanglah Hospital.

Definitions
Gastro-esophageal reflux disease (GERD):
Pathological reflux ranges from simple to
erosive to Barretts

Non-erosive reflux disease (NERD):

Reflux disease in which erosion does not
occur

Reflux Esophagitis:
- Symptoms or mucosal damage
(esophagitis)
due to exposure of
distal esophagus to reflux
gastric
content
Talley et al., BMJ 2001; 323: 12947.
de Caestecker, BMJ 2001; 323: 7369.
Nathoo, Int J Clin Pract 2001; 55: 4659.
Quigley, Eur J Gastroenterol Hepatol 2001; 13(Suppl 1): S1318.

THE MONTREAL DEFINITION &

CLASSIFICATION OF GERD
GERD is a condition which develops when the reflux
of gastric content causes troublesome symptoms
or complications
Esophageal
Syndromes

Symptomatic
Syndromes
Typical Reflux
Syndrome
Reflux Chest
Pain Syndrome

Syndromes
with Esophageal
Injury
Reflux Esophagitis
Reflux Stricture
Barretts Esophagus
Adenocarcinoma

Extra-esophageal
Syndromes

Established
Associations
Reflux Cough Syndr
Reflux Laryngitis
Reflux Asthma
Reflux Dental Eros.

Proposed
Associations
Pharyngitis
Sinusitis
Idiopathic
Pulmonary Fibrosis
Recurrent Otitis
Media

Vakil N et al. Am J Gastroenterol 2006

GastroEsophageal Reflux
Disease
GERD is a condition which develops when the reflux
of gastric content causes troublesome symptoms
or complications
Nonerosive GERD
(EGD negative)

Esophagitis

Stricture
Impairs Quality
of Life

Extraesophageal
GERD
ENT

Bleeding

Barretts Metaplasia
and
Adenocarcinoma

Asthma
Dental

EGD = esophagogastroduodenoscopy; ENT = ear, nose, and throat.

Range of presentations of GERD

Typical symptoms

Atypical symptoms

(Heartburn/regurgitation)

With
oesophagitis

Chest pain
(visceral
hyperalgesia)
Without
oesophagitis

(NERD=Non Erosive
Reflux Diseases)

Complications

Oesophageal
erosions
and/or ulcers
Stricture

Hoarseness
(reflux
laryngitis)

Asthma,
chronic cough,
wheezing
Dental erosions

Barretts
oesophagus

Oesophageal
adenocarcinoma
Nathoo, Int J Clin Pract 2001; 55: 4659.

PATHOGENESIS &
PATHOPHYSIOLOGY

GATRO-ESOPHAGEAL
GATRO-ESOPHAGEAL REFLUX
REFLUX DISEASES
DISEASES

Pathogenesis

Disturbance in esophageal clearance

TRLES (Transient Relaxation of LES)
LES dysfunction
Delayed gastric emptiying
Heartburn main symptom!
GERD is not an acid hypersecretion problem!

Pathophysiology of GERD
salivary HCO3
Impaired
mucosal
defence

oesophageal
clearance of acid
(lying flat, alcohol,
coffee)

Impaired LOS
(smoking, fat, alcohol)

Hiatus hernia

transient LOS
relaxations
basal tone

bile reflux

Bile and
pancreatic
enzymes

H+
Pepsin

acid output
(smoking, coffee)
intragastric pressure
(obesity, lying flat)
gastric emptying (fat)

de Caestecker, BMJ 2001; 323:7369.

Johanson, Am J Med 2000; 108(Suppl 4A): S99103.

Gastric acid refluxate and pepsin

destroy esophageal mucosa and
produces symptoms.
The dominant mechanism of symptom
production in reflux disease is by contact of
the esophageal mucosa with acid and pepsin
Genval statement 3, accepted completely

In the majority of people with reflux

disease there is abnormally prolonged
exposure of the distal esophagus to
acid and pepsinGenval statement 4, accepted completely
Dent et al 1999

Symptoms
Symptom

Predominance (%)

Heartburn

80

Regurgitation

54

Abdominal Pain

29

Cough

27

Dysphagia for solids

23

Hoarseness

21

Belching

15

Aspiration

14

Wheezing

Globus

Diagnosis of GERD
1. Based on typical GERD symptoms
- useful in primary health care / to all practitioners
- Use GERD questioner : all patients can be diagnosed

2. Therapeutic trial (PPI test=Empiric treatment)

- helpful for confirmed Diagnosis of GERD and NCCP

3. Gastroscopy
- patient with warning signs: vomiting, dysphagia,
odynophagia, GI bleeding, weight loss, Fe def anemia
- to diagnose of GERD complication

4. Other testings (reflux monitoring, manometry)

- to confirm diagnosis, prior to anti-reflux surgery

EGD

Allows examination of the esophageal

mucosa
Identifies presence of esophagitis and
grading of severity
Can identify other pathology, such as
diverticula, hiatal hernia, webs, rings, or
strictures
Tissue biopsies to screen for Barretts
esophagus

Alarm features for GERD

Odynophagia

Dysphagia

Bleeding
Alarm
features

Vomiting

Weight loss

Nathoo, Int J Clin Pract 2001; 55: 4659.

Following a symptom-based diagnosis, almost

all patients can be managed in primary care
Symptom-based
diagnosis
Alarm
symptoms

Risk
assessment

~60%Non-erosive
reflux disease

Endoscopy

~95% of
patients
in
primary
care1

Empirical
therapy
1

~35%

Reflux
esophagitis

~5% Complicated
reflux disease

Treatment
failure

DeVault KR, Castell DO. Am J Gastroenterol 2005;100:190200;

Rao G. J Fam Pract 2005;54 (12 Suppl):38.

Adapted from Labenz J et al.

World J Gastroenterol

The LA Classification system for the

endoscopic assessment of reflux esophagitis

Grade A:

One or more mucosal breaks no longer than 5

mm,
none of which extends between the tops of the
mucosal folds

Published with permission from Professor G Tytgat and Professor J Dent

The LA Classification system for the

endoscopic assessment of reflux esophagitis

Grade B: One or more mucosal breaks more than 5 mm

long, none of which extends between the tops of

two mucosal folds

Published with permission from Professor G Tytgat and Professor J Dent

The LA Classification system for the

endoscopic assessment of reflux esophagitis

Grade C: Mucosal breaks that are continuous between the

tops of two or more mucosal folds, but which
involve less than 75% of the esophageal
circumference

Published with permission from Professor G Tytgat and Professor J Dent

The LA Classification system for the

endoscopic assessment of reflux esophagitis

Grade D: Mucosal breaks which involve at least 75% of the

esophageal circumference

Published with permission from Professor G Tytgat and Professor J Dent

24-hour pH test

Gold Standard for

presence of
pathologic reflux
Parameters
measured include:
Total of reflux episodes,
duration of longest
reflux episode,
percentage of time pH
is less than 4

Ambulatory pH testing
Recent Advances

Combined
impedance and
acid testing
Allows for the
measurement of
both acid and
nonacid (volume)
reflux.
Important in pt with
persistent
symptoms despite
an adequate
medical trial

Ambulatory pH testing
Recent Advances

Tubeless method
Bravo System
Allows a radiotelemetry
capsule to be attached
to the esophageal
mucosa
Decreases patient
discomfort, allows for
longer (48h) monitoring,
and may improve
accuracy by allowing the
patient to carry out their
usual activities

Esophageal Manometry

Lower Esophageal
Sphincter (LES)
Mean resting pressure
Total length

Esophageal Body
To determine
effectiveness of
peristalsis
Amplitude of
esophageal wave

Esophagram

Useful when
operation is planned
shows anatomy of
esophagus and
proximal stomach
Demonstrates
presence and size of
hiatal hernia if
present

PPI test

PPI test for symptomatic GERD:1.

PPI high dose 2 x/ day, 7-14 days

Specificity 75-85%, sensitivity 55-73%

Positive response
GERD
PPI test for NCCP (Meta-analysis):2.

Sensitivity 80%, specificity 74%, compared with

placebo 19%

Indicative NCCP due to GERD: a

reduction > 50% of chest pain during
PPI therapy
1. Bautista J, et al. Aliment Pharmacol Ther, 2004;19:1123-30
2. Wang, WH et al. Arch Intern Med 2005;165:12228.

Differential diagnosis of GERD

Hiatus hernia
Oesophageal stricture
Oesophageal cancer
Chest pain of cardiac origin
Functional dyspepsia

Nathoo, Int J Clin Pract 2001; 55: 4659.

Treatment options
in GERD

Goals of Treatment

relief of pain and symptoms

decrease frequency and duration of reflux
promote healing
avoid complications (Barret's esophagus,
cancer)
prevent recurrence

GERD treatment options

Lifestyle
modifications
Tx of complication

Pharmacologic
tx:PPIs, H2RAs,

Approaches

Antacids,
Prokinetic
motility agents

Endoscopic
antirefluxproced
ure

Surgery

Hatlebakk & Berstad, Clin Pharmacokinet 1996; 31: 386

406.

Treatment of GERD
1. Lifestyle modification
- Almost always Recommended
(although mostly weak of evidence)

2. Pharmacologic treatment
- Step-down strategy is better than Step-up strategy
- Effective drugs: H2RA, Prokinetic, and PPI

2.A. Empirical / Initial therapy

2.B. Maintenance therapy
- On-demand vs Continuous vs intermitten

3. Anti-reflux surgery
- very selective cases only

INITIAL THERAPY

Mainstream options for therapy of

GERD
Highest efficacy

? x2 daily PPI + H2RA

x2 daily PPI

Recommended

x1 daily PPI

Current
guidelines

x1 daily PPI
Prokinetic + H2RA

Prokinetic*

Should be
abandoned

OR

H2RA*

Antacids + lifestyle
Antacids

Lowest efficacy
*no clear dose-response established

Lifestyle
after Dent et al 2002

I. Lifestyle modifications
1. Avoidance of foods that may precipitate reflux.
- e.g. coffee, alcohol, chocolate, fatty foods

2. Avoidance of acidic foods that may precipitate

heartburn. e.g. citrus, carbonated drinks, spicy foods
3. Adoption of behaviors that may reduce esophageal
acid exposure. e.g. reduced body weight, stop smoking,
- raising the head of the bed,
- avoiding recumbency less than 3 hours after meals

4. Good Practice: advice should be tailored to the

specific-related symptom of patient
AGA Institute. Gastroenterology 2008;135:13921413

Drug therapy

Symptomatic relief of GERD by: 1.

Placebo 27%, H2RA 60%, and PPI 83%

Esophagitis healed by: 1.

Placebo 24%, H2RA 50%, and PPI 78%

Relative Risk (RR) relief from heartburn increased

with greater degrees of acid suppression: 2.

Prokinetic :
H2RA
:
PPI
:

RR
RR
RR

0.86 (95% CI 0.73-1.01)

0.77 (95% CI 0.60-0.99)
0.37 (95% CI 0.32-0.44)

1. De Vault & Castell, Am J Gastroenterol 2005;100:190-200

2. Van Pinxteren et al. Cochrane Database Syst Rev 2004;(4):CD002095

Effectiveness of Medical Therapies for

GERD
Treatment

Response

Lifestyle modifications/antacids

20 %

H2-receptor antagonists

50 %

Single-dose PPI

80 %

Increased-dose PPI

up to 100 %

Step up or Step down treatment for

GERD

Long-term
treatment of
GERD

GERD is a Chronic Relapsing Condition

Esophagitis relapses quickly after

cessation of therapy
> 50 % relapse within 2 months
> 80 % relapse within 6 months

Effective maintenance therapy is

imperative

Treatment Modifications for Persistent

Symptoms

Improve compliance

Optimize pharmacokinetics
Adjust timing of medication to 15 30
minutes before meals (as opposed to
bedtime)
Allows for high blood level to interact with
parietal cell proton pump activated by the
meal

Consider switching to a different PPI

Maintenance Therapy in
GERD

On-demand PPI vs Continuous

PPIs are effective and safe
PPI
for short-term/ initial

therapy (8-12 weeks) and long-term therapy of GERD

patients (erosive esophagitis/ EE and non-erosive /
NERD).
Subset of GERD patients may still need maintenance
therapy to control the disease.
Two strategies of maintenance therapy: continuous
PPI or on-demand PPI

Trials result showed that on-demand therapy

are as effective as continuous therapy
Pace F, Porro GB Current Treat. Opt. in Gastroenterology 2008, 11:3542

Maintenance Treatment
Strategy Options
0

26 weeks

Continuous
maintenance

26 w
8w

8w

Intermittent

On Demand
(Step in)
S S

s = symptom recurrence