Gastroesophageal Gastroesophageal Reflux Disease Reflux Disease (GERD) (GERD) Dr. Kairu S. M. Dr. Kairu S. M.
Transcript
Slide 1
Slide 2
Gastroesophageal Reflux Disease (GERD) Dr. Kairu S. M.
Slide 3
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
Barretts 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 GERD - Definitions
Slide 4
Prevalence. Increased prevalence last 10 years. Increased
prevalence last 10 years. Accompanied increase in adenocarcinoma
lower esophagus. Accompanied increase in adenocarcinoma lower
esophagus. Obesity associated with increased GERD. Obesity
associated with increased GERD.
Slide 5
Anti Reflux Mechanism(ARM) This has both:- This has both:- (1)
Anatomical. (1) Anatomical. (2) Functional. (2) Functional.
Slide 6
Anatomical. 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 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. The outside (extrinsic) compression at the OG junction
from the crural diaphragm. Sharp angle- entry of esophagus into
stomach (angle of His). Sharp angle- entry of esophagus into
stomach (angle of His).
Slide 7
Slide 8
TLESR (Transient Lower Esophageal Sphincter Relaxations) A
normal phenomenon in healthy individuals. A normal phenomenon in
healthy individuals. Dominant mechanism of pathological reflux.
Dominant mechanism of pathological reflux. Too frequent TLESRs. Too
prolonged TLESRs.
Slide 9
Functional. Esophageal peristalsis that serves to clear luminal
contents into the stomach. Esophageal peristalsis that serves to
clear luminal contents into the stomach. Secretion and swallowing
of saliva to neutralize the acid and enhance clearance. Secretion
and swallowing of saliva to neutralize the acid and enhance
clearance. Prompt Gastric emptying. Prompt Gastric emptying.
Slide 10
Impaired mucosal defence salivary HCO 3 Hiatus hernia Impaired
LOS (smoking, fat, alcohol) transient LOS relaxations basal tone H
+ Pepsin Bile and pancreatic enzymes oesophageal clearance of acid
(lying flat, alcohol, coffee) acid output (smoking, coffee)
intragastric pressure (obesity, lying flat) bile reflux gastric
emptying (fat) Pathophysiology of GERD
Slide 11
Symptoms.
Slide 12
Heartburn and Regurgitation are the two cardinal symptoms of
GERD. Heartburn and Regurgitation are the two cardinal symptoms of
GERD. Others:- Others:- (1) Dysphagia-due to peptic stricture or
(1) Dysphagia-due to peptic stricture or peristaltic dysfunction.
peristaltic dysfunction. (2) Chest pain (NCCP). (2) Chest pain
(NCCP). (3) Water brash. (3) Water brash. (4) Globus Sensation. (4)
Globus Sensation. (5) Odynophagia. (5) Odynophagia.
Slide 13
Extra Esophageal Manifestations. 1. Asthma. 1) Microaspiration.
2) Vagal reflex activation. 2. Laryngitis. Complications of GERD.
Complications of GERD. a) Bleeding. b) Stricture. c) Barrets
esophagus adenocarcinoma
Slide 14
Role of Endoscopy in GERD. Confirm diagnosis of GERD -
erosions/ulcerations. Confirm diagnosis of GERD -
erosions/ulcerations. Diagnose endoscopy-negative reflux. Diagnose
endoscopy-negative reflux. Exclude other causes of esophagitis/
Exclude other causes of esophagitis/ odynophagia e.g.Candida,
Herpes Simplex. Diagnose complications of chronic GERD e.g Barrets
esophagus, stricture, adenocarcinoma. Diagnose complications of
chronic GERD e.g Barrets esophagus, stricture, adenocarcinoma.
Slide 15
1.Savary-Miller classification. 1. Solitary erythematous
/erosions covering one mucosal fold. 2. Solitary erythematous
/erosion covering more than one mucosal folds but not
circumferential. 3. Circumferential erythematous / erosions. 4.
Complications Ulcers. Ulcers. Strictures. Strictures. Barretts
esophagus. Barretts esophagus.
The Step up Approach. PPI PPI LOW DOSE PB. LOW DOSE PB. H2RA
+PROKINETIC. H2RA OTC ANTACIDS + LIFESTYLE ADVICE.
Slide 30
The Step Down Approach. PPI PPI LOW DOSE PB. LOW DOSE PB. H2RA
+PROKINETIC. H2RA +PROKINETIC. H2RA+LIFESTYLE ADVICE.
H2RA+LIFESTYLE ADVICE. OTC ANTACIDS. OTC ANTACIDS.
Slide 31
Long Term Therapy. Many patients, GERD a chronic relapsing
problem because the underlying motor abnormalities persist. Many
patients, GERD a chronic relapsing problem because the underlying
motor abnormalities persist. PPIs. PPIs. Majority of patients
require PPI even in low doses. Majority of patients require PPI
even in low doses. Occasional patients may require high doses
(double dose of PPI to control symptoms.) Occasional patients may
require high doses (double dose of PPI to control symptoms.)
Nocturnal acid breakthrough. Nocturnal acid breakthrough.
Slide 32
Surgery in GERD Nissan Fundoplication Surgery in GERD Nissan
Fundoplication 40-50% have required medical treatment after
surgery. 40-50% have required medical treatment after surgery. High
failure rate. Mortality operator dependent. Mortality operator
dependent. Morbidity / complications: ~ 10% dysphagia requiring
repeated esophageal dilatation. Morbidity / complications: ~ 10%
dysphagia requiring repeated esophageal dilatation.
Slide 33
Potential Risks of Chronic PPI Therapy Hypergastrinemia,
carcinoids Hypergastrinemia, carcinoids Gastritis, intestinal
metaplasia, gastric cancer Gastritis, intestinal metaplasia,
gastric cancer Achlorhydria and loss of gastric sterility
Achlorhydria and loss of gastric sterility Increased enteric
infections, C, difficile. Increased enteric infections, C,
difficile. N-nitrosamine and carcinogen risk N-nitrosamine and
carcinogen risk Community =acquired pneumonia Community =acquired
pneumonia Safety during pregnancy /lactation Safety during
pregnancy /lactation Drug interactions. Drug interactions.
Slide 34
Potential Risks of Chronic PPI Therapy Hypergastrinemia,
carcinoids RATS Elevated gastrin ECL cell hyperplasia ECL cell
carcinoid tumors HUMANS Elevated gastrin ECL cell hyperplasia NO
CARCINOID TUMORS Species specific problem (rat) Up to 8 year
continuous use in patients (as of 2000)
Slide 35
Potential Risks of Chronic PPI Therapy Achlorhydria,
N-nitrosamine generation The RISKThe REALITY Achlorhydria permits
growth of bacteria that can convert nitrates to nitrites to N-
nitrosamine (carcinogen) 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
Slide 36
Potential Risks of Chronic PPI Therapy Achlorhydria, enteric
infection The RISK The REALITY Achlorhydria disables the gastric
barrier to ingested pathogens 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 PPIs have been reported.
Garcia Rodriguez LA et al. Epidemiol 1997:8:571-4, Dial S et al
CMAJ 2004: 171: 33-8
Slide 37
Potential Risks of Chronic PPI Therapy Community acquired
pneumonia The RISKThe REALITY Gastric colonization followed by
reflux and aspiration of gastric contents results in pneumonia
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
Slide 38
Potential Risks of Chronic PPI Therapy Safety during
pregnancy/lactation The RISKThe REALITY Omeprazole crosses
placenta, category C; Other PPIs 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 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 Servicesthe PPIs do not represent a major
teratogenic risk in humans Diav-Citrin O et al, Aliment Pharmacol
Ther 2005: 21: 269-75
Slide 39
PPIs: Adverse Events/Effects Clopidogrel Clopidogrel
Prospective studies of platelet aggregation. Retrospepctive studies
of clinical outcomes. Randomized, double-blind trail of PPI vs
placebo among clopidogrel users. No difference in cardiac events,
mortality No difference in cardiac events, mortality Significant
reduction in GI events with PPI Significant reduction in GI events
with PPI
Slide 40
GABA Agonist Baclofen Baclofen 40mg Baclofen 40mg Reduced
TLESRs in patients with GERD Reduced esophageal acid exposure
Limitations Limitations CNS side-effects mainly drowsiness. Short
half-life. Van Herwaarden et al. Aliment Phar,acol Ther 2002
Slide 41
New motility agent (GABA Agonist) Lesogaberan Lesogaberan a
peripheral acting GABA agonist. Lesogaberan a peripheral acting
GABA agonist. Study showed 35% in TLESR. Study showed 35% in TLESR.
A potential agent for treatment of GERD as co- therapy. A potential
agent for treatment of GERD as co- therapy.
Slide 42
Summary PPIs remain the standard treatment for GERD. PPIs
remain the standard treatment for GERD. Well established to be very
safe. Well established to be very safe. Prevalence of GERD
increasing with increase in lower esophageal adenocarcinoma.
Prevalence of GERD increasing with increase in lower esophageal
adenocarcinoma. New motility drugs in development Lesogaberan. New
motility drugs in development Lesogaberan.