Pathophysiology of GERD

and its complication

 Introduction
• GERD is frequent and rising in Indonesia.
• GERD decreases the quality of life.
• Pathophysiology and risk factors  GERD
• Treatment depends on pathophysiology.
GASTROESOPHAGEAL REFLUX
DISEASE (GERD)
• The Incidence of GERD: USA 7-10%
French/Sweden 12-40% , Asia 1.5-2.7%
• GERD 45-89% in bronchial asthma, The
prevalence of GERD in patients with bronchial
asthma 2x in patients without bronchial asthma
• GERD relaps & disturbing
• Chronic GERD: 85-90% relaps 6 months after
PPI
• GERD complications: Stricture, Barrett’s
esophagus & Cancer
GERD FKUI/RSCM , JAKARTA

• Dyspeptic patient :
•Endoskopi , Esophagitis 22,8 %
• 90 % mild esophagitis
Lelosutan 1998
• Increased of prevalence of patients
dyspepsia ( n= 1718 )
• 1997 : 5,7%
• 2002 : 25,18 %
mean 13,13 %
Syam AF, 2003
 GERD— is not just “ heartburn”

Definition Montreal : GERD is a condition caused by the reflux of

gastric contents which causes symptoms and /or complication

Extraesophageal
Esophageal Syndrome
Syndrome

Symptoms Esophageal damage Clear correlation Unclear correlation

1. Reflux 1. Pharyngitis
1. Reflux cough 2. Sinusitis
esophagitis
1. Typical Reflux 2. Reflux Stricture 2. Reflux laryngitis 3. Idiopathic
2. Chest pain 3. Barrett’s 3. Reflux asthma Pulmonary
caused by reflux Esophagus 4. Reflux dental Fibrosis
4. Esophageal 4. Recurrens Otitis
erosion
Adenocarcinoma Media

Vakil N, et al. Am J Gastroenterol 2006;101:1900–1920

3 Unique Groups of GERD with longterm
consequences
 Range of presentations of GORD

Typical
symptoms Atypical
(Heartburn/regurg symptoms Complications
itation)

With Chest pain Oesophageal

oesophagitis (visceral erosions
and/or ulcers
hyperalgesia)
Without Hoarseness Stricture
oesophagitis (‘reflux
laryngitis’)

Asthma, Barrett’s
chronic oesophagus
cough,
wheezing
Nathoo, Int J Clin Pract Dental erosions Oesophageal
2001; 55: 465–9. adenocarcinoma
 Pathophysiology of GERD
• Abdominal transient lower esophageal
sphincter relaxation(TLESR) reaction.
• Hypersensitivity of the esophageal
mucosa to stimuli.
• Delayed gastric emptying.
• Decreased ability to clear the contents of
reflux.

Yoshida N et.al. Dig Dis Sci 2009

 Causes of increased exposure of
the esophagus to gastric refluxate

Defective esophageal
clearance

LES ‘dysfunction’
Hiatal hernia

Delayed gastric emptying

Increased intra-abdominal pressure

Katzka DA, DiMarino AJ. In: The esophagus, second edition, Castell DO (editor).
Little, Brown & Company, Boston, USA. 1995:443–53.
 Pathophysiology of GERD
• GERD results when there is imbalance between
aggressive and defensive mechanisms, favoring
aggressive factors.
• The aggressive factors are: gastroduodenal factors such
as acid and pepsin, duodenal contents: bile, trypsin,
Helicobacter pylori, & gastric emptying.
• The defensive factos are: esophageal factors and
gastroesophageal junction factors.
• The esophageal factors are: peristalsis, saliva, epithelial
defense and repair.
• The gastroesophageal junction are: transient LES
relaxations, hypotensive LES, & hiatal hernia.

Vela MF et.al. The Pathophysiology of GERD. In Hot Topics GERD/Dyspepsia.2004.

 Factors in the pathophysiology IN GERD
a. Incompetent LES: hiatal hernia, short LES, drugs
(anticholinergic, beta adrenergic agonist, theophylline,
benzodiazepine, calcium channel blocker, opiate),
hormones(pregnancy, increased progesterone,
cholecystokinine, secretine)
b. Transient LES relaxation(TLESR)
c. Decreased or delayed acid clearance from the
esophagus.
d. Gastric abnormality: gastric dilatation, pyloric
obstruction, delayed gastric emptying
e. Decreased mucosal epithelial resistency
f. The refluxate chemical composition, gastric acid,
pepsin or bile. Some food like citroen acid, tomato and
coffee increased GERD.
 Acid reflux parameters in relation to endoscopic
grading of mucosal breaks

Number % time Number of reflux

of pH < 4 episodes
patients

Normal grade 40 6.7(1.0) 59.5(12.8)

Grade A 50 9.3(1.3) 106.9(12.8)
Grade B 50 13,7(2.1) 138.3(20.0)
Grade C 9 11.7(3.0) 135.8(29.4)
Grade D 10 19.1(6.6) 163.0(41.7)
C+D 19 15.6(3.8) 150.1(25.5)

Results expressed as mean(SEM)

Normal versus A,B,C,D, p=0.007; Normal + grade A versus grade B,C,D, p=0.003;
normal + A,B versus grade C,D, p=0.001

Lundell LR et.al. Gut 1999

 Acid-peptic attack (1) weakens cell junctions (2) leading
to a widening of cell gaps and thus allowing increased
acid penetration (3)

1 2 3

Tight cell Acid Widened

junction Pepsin cell
Nerve ending
Bicarbonate junction
 Penetration of acid and pepsin allows contact of
acid with nerve endings (4) and disrupts intracellular
mechanisms leading to cell rupture and mucosal damage (5)

4 5

Acid
Pepsin
Bicarbonate

Nerve
ending
Pathophysiology of GERD
 Risk Factors for GERD

• Exogenous(environmenal) risk factor

• Endogenous risk factor: genetic, other
comorbid disease
Table 1. Environmental(Exogenous) Risk Factor for GERD
Risk Factor Mechanism of Risk
Smoking Weakened LES? (small risk)
Alcohol Mucosal damage? (small risk)
Medications Weakening of LES, mucosal damage
Meals and specific foods Gastric distension, weakening of LES irritation of esopageal
mucosa
Helicobacter pylori Beneficial influence as corpus gastritis reduces acid output
Naso-gastric tubes Conduct for acid reflux in supine patients
Abdominal trauma Disruption of diaphragm?

LES = lower esophageal sphincter

 Table 2. Medical conditions associated with
Gastroesohageal Reflux Disease
Associated Condition Mechanism of Risk
Obesity Increased intra-abdominal pressure
Diabetes Mellitus Delayed gastric emptying
Zollinger-Ellison syndrome Increased acid output
Pregnancy Increased intra-abdominal pressure, weakened LES
Myotomy in Achalasia Destroyed LES
CSRT syndrome Impaired peristalsis
Sicca syndrome Impaired esophageal clearance
Psychiatric disease Impaired esophageal motility
Mental retardation of childhood Impaired esohageal motility

LES = Lower esophageal sphincter

Vela MF et.al. The Pathophysiology of GERD. In Hot Topics GERD/Dyspepsia.2004.

Why GERD increases in Asia ?

• Ethnical factor;
Multi-race Malaysia : GERD India / china: risk 3,25
Melayu/china: risk 1,67
• BMI : > 25 OR 1,41
• Hiatus Hernia OR 4,21
• Alcohol OR 2,42
• Fatty food OR 6,56
• Over eating OR 1,99
 Complications
• Stricture
• Upper gi bleeding
• Perforation
• Esophageal cancer.
 Conclusion
• Pathophysiology of GERD is imbalance of
aggressive and defensive factors, favoring
the aggressive factor.
• There are risk factors for GERD:
endogenous and exogenous.
• The complications of GERD: stricture,
Upper gi bleeding, perforation, esophageal
cancer.