Transcript Gastroesophageal Reflux Disease ( GERD)

Gastroesophageal Reflux
Disease (GERD)
Dr. Kairu S. M.
GERD - Definitions
Gastro-oesophageal reflux disease (GORD):
Abnormal reflux of gastric juice (acid and bile) into the oesophagus
leading to symptoms
Pathological reflux ranges from simple to erosive to Barrett’s
Non-erosive reflux disease (NERD):
Reflux disease in which erosion does not occur
Heartburn:
Burning retrosternal pain radiating upward due to exposure
of the oesophagus to acid
Oesophagitis:
Endoscopically demonstrated damage to the oesophageal
mucosa
Prevalence.
 Increased
prevalence last 10 years.
 Accompanied
increase in
adenocarcinoma lower esophagus.
 Obesity
GERD.
associated with increased
Anti Reflux Mechanism(ARM)

This has both:(1) Anatomical.
(2) Functional.
Anatomical.
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The lower esophageal sphincter (LES) at the
OG junction consists of tonically contracted
smooth muscle at approx. 8-20 mmHg above
the gastric pressure.
The outside (extrinsic) compression at the OG
junction from the crural diaphragm.
Sharp angle- entry of esophagus into stomach
(angle of His).
TLESR
(Transient Lower Esophageal Sphincter Relaxations)

A normal phenomenon in healthy
individuals.
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Dominant mechanism of pathological
reflux.
–
–
Too frequent TLESRs.
Too prolonged TLESRs.
Functional.
Esophageal peristalsis that serves to clear
luminal contents into the stomach.
 Secretion and swallowing of saliva to
neutralize the acid and enhance clearance.
 Prompt Gastric emptying.

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
H+
Bile and
pancreatic
enzymes
Pepsin
acid output
(smoking, coffee)
intragastric pressure
(obesity, lying flat)
bile reflux
gastric emptying (fat)
Symptoms.
Heartburn and Regurgitation are the two cardinal
symptoms of GERD.
 Others:(1) Dysphagia-due to peptic stricture or
peristaltic dysfunction.
(2) Chest pain (NCCP).
(3) Water brash.
(4) Globus Sensation.
(5) Odynophagia.

Extra Esophageal Manifestations.
2.
Asthma.
1) Microaspiration.
2) Vagal reflex activation.
Laryngitis.

Complications of GERD.
a)
Bleeding.
Stricture.
Barrets esophagus adenocarcinoma
1.
b)
c)
Role of Endoscopy in GERD.
Confirm diagnosis of GERD erosions/ulcerations.
 Diagnose endoscopy-negative reflux.
 Exclude other causes of esophagitis/
odynophagia e.g.Candida, Herpes
Simplex.
 Diagnose complications of chronic
GERD e.g Barrets esophagus, stricture,
adenocarcinoma.

1.Savary-Miller classification.
1.
2.
3.
4.
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Solitary erythematous /erosions covering one
mucosal fold.
Solitary erythematous /erosion covering more
than one mucosal folds but not circumferential.
Circumferential erythematous / erosions.
Complications
Ulcers.
Strictures.
Barrett’s esophagus.
Grade I
Grade 1
Grade 2
Grade 2
Grade 2
Grade 3
Grade 4
Grade 4
Grade 4
Grade 4.
Modes of Treatment

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Proton Pump Inhibitors
– Longer acting PPI’s.
– Adverse events/effects of PPIs.
Potassium –competitive acid blockers (PCABs)
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Motility agents.
– GABA agonists
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Endoscopic therapy
– Full-thickness plication
The Step up Approach.
PPI

LOW DOSE PB.

H2RA +PROKINETIC.

H2RA

OTC ANTACIDS + LIFESTYLE ADVICE.
The Step Down Approach.

PPI

LOW DOSE PB.

H2RA +PROKINETIC.

H2RA+LIFESTYLE ADVICE.

OTC
ANTACIDS.
Long Term Therapy.
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Many patients, GERD a chronic relapsing
problem because the underlying motor
abnormalities persist.
PPI’s.
Majority of patients require PPI even in low
doses.
Occasional patients may require high doses
(double dose of PPI to control symptoms.)
Nocturnal acid breakthrough.
Surgery in GERD
Nissan Fundoplication

40-50% have required medical treatment after
surgery.
–
High failure rate.

Mortality – operator dependent.
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Morbidity / complications: ~ 10% dysphagia
requiring repeated esophageal dilatation.
Potential Risks of Chronic PPI
Therapy
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Hypergastrinemia, carcinoids
Gastritis, intestinal metaplasia, gastric cancer
Achlorhydria and loss of gastric sterility
•
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•
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Increased enteric infections, C, difficile.
N-nitrosamine and carcinogen risk
Community =acquired pneumonia
Safety during pregnancy /lactation
Drug interactions.
Potential Risks of Chronic PPI Therapy
Hypergastrinemia, carcinoids
RATS
HUMANS
•Elevated gastrin
•Elevated gastrin
•ECL cell hyperplasia
•ECL cell hyperplasia
•ECL cell carcinoid tumors
•NO CARCINOID TUMORS
Species specific problem (rat)
Up to 8 year continuous use in patients (as of 2000)
Potential Risks of Chronic PPI Therapy
Achlorhydria, N-nitrosamine generation
The RISK
• Achlorhydria permits
growth of bacteria that
can convert nitrates to
nitrites to N- nitrosamine
(carcinogen)
The REALITY
• Increased UGI bacteria has
been detected in PPI takers.
•N-nitrosamine formation is
also catalyzed by acid.
Data on PPI use and increased gastric N-nitrosamine remain
uncertain and the cancer risk is speculative
Potential Risks of Chronic PPI Therapy
Achlorhydria, enteric infection
The RISK
• Achlorhydria disables the
gastric barrier to ingested
pathogens
The REALITY
•Case-control study: Small increase in enteric infections with
PPIs for 2 months.
–Relative risk 1.6 (Cl 1.0-2.4)
•PPPI use is independent risk of C. difficile diarrhea in
antibiotic users.
–PPI use OR 2.1 (Cl 1.2-3.5)
–≥3 AB OR 2.1 (Cl 1.3-3.4)
–Medical ward OR 4.1 (Cl 2.3-7.3)
Only occasional cases of enteric infections in patients taking PPI’s have been
reported.
Garcia Rodriguez LA et al. Epidemiol 1997:8:571-4, Dial S et al CMAJ 2004: 171: 33-8
Potential Risks of Chronic PPI Therapy
Community –acquired pneumonia
The RISK
 Gastric colonization followed by
reflux and aspiration of gastric contents
results in pneumonia
The REALITY
 Case-control Dutch primary case
database 1/1/95-12/31/2002.
–364,683 Individuals
–5551 1st Pneumonias
–PPI user risk 0.60/100 pt yrs
Nested case control analysis to reduce
confounding effects of indication
–Non-PPI user risk 0.60/100 pt yrs
Adjusted OR all 1.27 (Cl 1.06-1.54)
–Adjusted OR PPI 1.73 (Cl 1.33-2.25)
Association does not prove causation
PPI takers are also more likely to smoke, drink, be obese, have GERD, and ??
(note how OR 4.08 dwindled to 1.73)
Laheji RJ et al. JAMA 2004: 292: 1955-60
Potential Risks of Chronic PPI Therapy
Safety during pregnancy/lactation
The RISK
Omeprazole crosses placenta,
category C; Other PPI’s
category B
A. controlled human studies no
risk.
B. animal studies or, adverse fetal.
C. no adequate studies or, adverse
fetal effects in animals at some
dose.
D. evidence of fetal risk: benefit >
risk
X. Evidence of fetal risk: benefit <
risk
The REALITY
1992-2001 prospective
controlled evaluation of PPI
gestational exposures
–Omeprazole: 247 births
3.6% major anomalies.
–Lansoprazole: 50 births,
3.9% MA
–Pantoprazole: 48 births,
2.1% MA
–Controls: 787 births,
3.8%MA
European Network of Teratology Information Services…the PPI’s do not
represent a major teratogenic risk in humans
Diav-Citrin O et al, Aliment Pharmacol Ther 2005: 21: 269-75
PPI’s: Adverse Events/Effects
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Clopidogrel
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Prospective studies of platelet aggregation.
Retrospepctive studies of clinical outcomes.
Randomized, double-blind trail of PPI vs
placebo among clopidogrel users.
•
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No difference in cardiac events, mortality
Significant reduction in GI events with PPI
GABA – β Agonist
Baclofen
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Baclofen 40mg
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Reduced TLESR’s in patients with GERD
Reduced esophageal acid exposure
Limitations
–
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CNS side-effects mainly drowsiness.
Short half-life.
Van Herwaarden et al. Aliment Phar,acol Ther 2002
New motility agent (GABA β Agonist)
Lesogaberan
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Lesogaberan – a peripheral acting GABA β
agonist.
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Study showed 35% ↓ in TLESR.

A potential agent for treatment of GERD as cotherapy.
Summary
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PPI’s remain the standard treatment for GERD.

Well established to be very safe.
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Prevalence of GERD increasing with increase in
lower esophageal adenocarcinoma.
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New motility drugs in development – Lesogaberan.
THE END