INTRODUCTORY LECTURE:

Reflux esophagitis

Oleh:
PROF. DR Dr I DEWA NYOMAN WIBAWA SpPD-KGEH
Div.Gastroenterologi-hepatologi,
Bag.I.P.Dalam FK Unud/RS Sanglah.
Definitions

Heartburn:
– Burning retrosternal pain radiating upward due
to exposure of the oesophagus to acid
Oesophagitis:
– Endoscopically demonstrated damage to the
oesophageal mucosa
Gastro-oesophageal reflux disease (GORD):
– Pathological reflux ranges from simple to
erosive to Barrett’s
Non-erosive reflux disease (NERD):
– Reflux disease in which erosion does not occur

Talley et al., BMJ 2001; 323: 1294–7.

de Caestecker, BMJ 2001; 323: 736–9.
Nathoo, Int J Clin Pract 2001; 55: 465–9.
Quigley, Eur J Gastroenterol Hepatol 2001; 13(Suppl 1): S13–18.
Reflux esophagitis is defined as

 Symptoms or mucosal Damage (esophagitis)

 Due to exposure of distal esophagus to
reflux gastric content
THE MONTREAL DEFINITION &
CLASSIFICATION OF GERD
 The Spectrum of GER
Physiological Symptomatic Esophagitis Complicated
Reflux GERD Esophagitis

Typical Atypical
* Heartburn * Chest pain
* Regurgitation * Cough
* Water brash * Asthma
* Laryngitis
* Dysphagia
Range of presentations of GERD

Typical symptoms
(Heartburn/regurgitation)
Atypical symptoms Complications

With Chest pain Oesophageal

erosion (visceral erosions
hyperalgesia) and/or ulcers

Without erosion Hoarseness Stricture

(‘reflux
laryngitis’)
(NERD=Non Erosive
Reflux Diseases)
Asthma, Barrett’s
chronic cough, oesophagus
wheezing

Dental erosions Oesophageal

adenocarcinoma

Nathoo, Int J Clin Pract 2001; 55: 465–9.

3 Distinct groups of GERD diseases

1. Erosive esophagitis (EE) : leading to stricture,

ulcer and bleeding
2. Complicated GERD including Barrett's
esophagus: leading to adenocarcinoma of the
esophagus
3. Non-erosive reflux disease (NERD) : with
atypical or extra-esophageal Manifestations and
no esophageal mucosal injury

Fass, R.; USA

 Does GERD Progress ?

Symptomatic Esophagitis Barrett’s

GERD
PRGE - 3 Kelompok unik pasien

Non-Erosive Erosive Barrett’s

Reflux Disease Esophagitis Esophagus

Non-progressive Stricture Adenocarcinoma

Atypical Ulcer of the
manifestations GI bleeding esophagus
 Atypical reflux symptoms
An association with GERD may occur in:
 Non-cardiac chest pain. GERD symptoms are an
independent predictor of this condition
Talley et al 1999

 Chronic hoarseness and persistent cough. These

problems may be due to refluxed gastric acid, although
typical GERD symptoms may occur in only 20-40% of
cases
 Asthma. Typical GERD symptoms are not apparent in
one third of asthma patients with esophageal
dysfunction
Mujica & Rao 1999
Atypical respiratory
symptoms
GERD can be a trigger
for asthma

100
Asthma patients experiencing GORD

80 77
72
65
symptoms (%)

60

40

20

0
Perrin-Fayolle et al. O’Connell et al. Field et al.
(n=150) (n=189) (n=109)

Harding & Sontag, Am J Gastroenterol 2000; 95(Suppl): S23–32.

Mechanism of asthma symptoms on
exposure to oesophageal acid

Asthma symptoms
plus oesophageal
acid

Oesophageal acid-induced Increase:

bronchoconstriction:  minute ventilation
 vagally mediated oesophageal  respiratory rate
bronchial reflex
 heightened bronchial reactivity
 microaspiration

Evidence of airway inflammation:

 Substance P and tachykinin

release

Harding & Sontag, Am J Gastroenterol 2000; 95(Suppl): S23–32.

 Prevalence of GERD

 Community prevalence of reflux symptoms

(heartburn, regurgitation)
 Prevalence of endoscopic esophagitis among
patients undergoing upper-endoscopy (endos-
copic population)
 Community prevalence of heartburn
(%) in different populations
Author Country Sample Age group %
Size (years)
Western countries :
Drossman et al. (1993) USA 5430 > 18 32.6
Agreus et al. (1994) Sweden 1156 19-79 16.7
Kay et al. (1994) Denmark 3608 30-60 38
Locke et al. (1997) USA 1511 25-74 42.4
Deltenre et al. (1998) Belgium 3000 35 and above 28.1
Locke et al. (1999) USA 1524 25-74 41
Oriental countries :
Ho et al. (1998) Singapore 696 21-95 1.1
Wong et al. (2003) China 2209 > 18 8.9
Global prevalence of non-erosive reflux disease
and erosive esophagitis in gastroesophageal
reflux disease
 Prevalence GERD
 20% di United Kingdom pasien dyspepsia mengalami refluk Esofagitis
( Ricter 1991 )
 8% usia dewasa di Amerika mengalami heart burn atau regurgitasi dua
sampai lebih dalam satu minggu.

( Louis Harris &Associates 1997 )

 Data di RSCM Jakarta 22.8% pasien dengan keluhan dyspepsia
mengalami refluk Esofagitis ( Syafruddin,manan 1999)
 RS Sutomo Surabaya 16% pasien dyspepsia mengalami Refluk
Esofagitis ( Hernomo,2000 )
GASTRO-ESOPHAGEAL REFLUX DISEASES

Hernia- Refluks Eso- Esofag. Adeno-

hiatal patologis fagitis Barret carcin.

50% 10% 10% 10% 10%

50% 5% 0.5% 0.05% 0.005%

PATHOGENESIS &
PATHOPHYSIOLOGY
GASTRO-ESOPHAGEAL REFLUX DISEASES

Pathogenesis
• LES dysfunction.
• Abnormal esophageal clearance
• TRLES (Transient Relaxation of LES)
• Delayed gastric emptying
Heartburn: main symptom!
GERD is not an acid hypersecretion problem!
ESOPHAGEAL DEFENSES
1. First Line:
antireflux barriers
2. Second Line
luminal clearance
3. Third Line
epithelial resistance

OFFENSE
POTENCY OF REFLUXATE
a. Gastric secretion
b. Pyloric competence
HCI

Pepsin
ic
li e reat
B nc
es
Pa zym
en
(Orlando, 1995)
 Anti Reflux Mechanism
Saliva
&Esoph.motility

Diaphrag Mucosal
aposition LES tone
ma Cruz

Intra
Abd.press.
Angle
of His

Prompt Gastric
emptying
Pathophysiology of GORD

salivary HCO3
Impaired
mucosal oesophageal
defence clearance of acid
(lying flat, alcohol,
coffee)
Impaired LOS
(smoking, fat, alcohol) Hiatus hernia
– transient LOS
relaxations acid output
H+
(smoking, coffee)
– basal tone Bile and
Pepsin
pancreatic
enzymes
intragastric pressure
(obesity, lying flat)

bile reflux gastric emptying (fat)

de Caestecker, BMJ 2001; 323:736–9.

Johanson, Am J Med 2000; 108(Suppl 4A): S99–103.
Refluksat asam lambung dan pepsin,merusak
mukosa esophagus serta penyebab
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 pepsin”

Genval statement 4, accepted completely

Dent et al 1999
Diagnosis and
management
of GERD
Alarm features for GORD

Odynophagia

Dysphagia Bleeding

Alarm
features

Vomiting Weight loss

Nathoo, Int J Clin Pract 2001; 55: 465–9.

GERD: DIAGNOSIS
 SYMPTOMS
 PPI TEST
 ENDOSCOPIC DX
 OTHER DX TEST
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 Den

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 Den

 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 Den

 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 Den

Differential diagnosis of GORD

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

Nathoo, Int J Clin Pract 2001; 55: 465–9.

 PPI TEST
 STANDARD DOSE OR DOUBLE DOSE
 7-(14) DAYS
 POS RESPOND: SUGGESTIVE GERD
 NEG: EXCLUDE DX
GASTRO-ESOPHAGEAL REFLUX DISEASES

OTHER DX TEST

• Barium Swallow
• 24 HRS pH MONITORING
• Manometry
Penyakit
Penyakit Refluks
Refluks Gastroesofageal
Gastroesofageal (PRGE)
(PRGE)
 GASTRO-ESOPHAGEAL REFLUX DISEASES

American College of Gastroenterology Guidelines 1999

pH dan TES PROVOKASI

 Konfirmasi GE reflux, terbaik utk keluhan persistent

endoskopi negatip (NERD). non-cardiac
chest pain (NCCP), keluhan berhub. paru dan
laring.
 untuk monitor paparan asam pada esofagus
pada simptom refrakter.
 tes provokatif: manfaat terbatas
 GASTRO-ESOPHAGEAL REFLUX DISEASES

American College of Gastroenterology Guidelines 1999

Diagnosis: MANOMETRI ESOFAGUS

 facilitates placement of ambulatory pH probes

 valuable pre-op evaluation for indications

of anti-reflux surgery
GERD complication

Ulserasi
Striktura

Adeno karsinoma
Treatment options
in GERD
Available Therapeutic Options in GERD

Wide spectrum of non-invasive and less expensive options

and invasive and expensive options
 Lifestyle modifications
 Antacids
 Prokinetics
 H2RAs
 PPIs
 Endoscopic anti-reflux procedures
 Surgery (laparoscopic/open)
 Management of complications
GORD treatment options

Lifestyle Antacids
modifications

PPIs Approaches H2RAs

Prokinetic Surgery
motility agents

Hatlebakk & Berstad, Clin Pharmacokinet 1996; 31: 386–

406.
Lifestyle Modifications for Patients
With Reflux Esophagitis

 Elevate the head of the bed 6 inch

 Stop smoking
 Stop excessive alcohol consumption
 Reduce dietary fat
 Reduce meal site
 Avoid bedtime snacks
 Weight reduction (if patient is
overweight)

(From Orlando RC. Gastroesophageal reflux : medical treatment. In : Byless TM, ed.
Current therapy in gastroenterology and liver disease. 3rd end. Philadelphia BC Decker,
1989,7)
Lifestyle modifications for the
management of GORD

Reduce weight

Elevate head
Stop smoking
of bed

Modifications
Avoid reflux-promoting
agents (e.g. alcohol, Consider
coffee, some foods) alternatives to
(not evidence based) reflux-promoting drugs
(e.g. theophylline,
anticholinergics)
Eat small meals,
no late meals,
reduce fat
MEDICATION THERAPY
1. Acid suppressive drugs
H2-receptor antagonists



Proton pumps inhibitor

2. Prokinetics
3. Liquids antacids
4. Cytoprotective
Antacids
Increase the pH of gastric refluxate

Reduce the erosive effect and hence reduce symptoms
Suitable for quick relief of mild symptoms
Most antacids are not suitable therapies for established
GORD or oesophagitis

Less effective than H2RAs or PPIs for treatment of GORD
Adverse effects include:

Accumulation in patients with renal impairment

Milk-alkali syndrome with high doses

Constipation

Diarrhoea
Sonnenberg A, Pharmacoeconomics 2000; 17: 391–401.
de Caestecker, BMJ 2001; 323: 736–9.
Hatlebakk & Berstad, Clin Pharmacokinet 1996; 31: 386–406.
Scott & Gelhot, Am Fam Physic 1999; 59: 1161–9.
Prokinetic motility agents

Increase LOS pressure and enhance gastric

emptying
Relieve heartburn but do not heal oesophagitis
Cisapride was used in GORD treatment in
the past

Lansoprazole (PPI) has superior efficacy to
cisapride in GORD

The risk of cardiac side effects with cisapride
now excludes this agent from use in GORD

van Rensburg et al., Gastroenterology 2000; 118(Suppl 2): A1318.

de Caestecher, Eur J Gastroenterol Hepatol 2002; 14: 5–7.
de Caestecker, BMJ 2001; 323: 736–9.
Dent et al., BMJ 2001; 322: 344–7.
H2-receptor antagonists (H2RAs)

Inhibit histamine stimulation of gastric parietal

cell, resulting in reduced gastric acid secretion
Slower onset but longer duration of action
than antacids
Cimetidine is associated with more drug
interactions than other H2RAs, such as ranitidine
H2RAs are generally not as effective as PPIs for
symptom relief or healing

de Caestecker, BMJ 2001; 323: 736–9.

Sonnenberg, Pharmacoeconomics 2000; 17: 391–401.
Available PPIs

Omeprazole
Lansoprazole
Pantoprazole
Rabeprazole
Esomeprazole
GERD
GERD
American College of Gastroenterology Guidelines 1999

EMPIRIC ACID SUPPRESSION THERAPY

Uncomplicated GERD: empiric therapy,

include lifestyle changes
Unsuccessful Empiric Therapy
Symptoms of Complicated Disease: diagnostic testing

Prolonged Symptoms screening endoscopy

Requiring Continuous Therapy: for Barretts
Step up or Step down treatment for GERD
Manajemen PRGE jangka panjang

PRGE erosiv PRGE non-erosiv

 PPI dosis tinggi sampai  Fokus pada keluhan

sembuh sempurna (8  Step down terapi
minggu) jangka panjang
 Pertimbangkan  On demand terapi
pengobatan jangka cukup memadai
panjang untuk cegah
komplikasi
Maintenance Treatment
Strategy Options
0 26 weeks

Continuous
26 w
maintenance

8w 8w Intermittent

S S

“On Demand”
(Step in)
S S S S S S

s = symptom recurrence