Gastroesophageal reflux disease

(GERD)

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Raika Jamali M.D.

Gastroenterologist and hepatologist

Sina Hospital

Tehran University of Medical Sciences

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Definition of GERD according to �Geneva Workshop

• The term GERD should be used for individuals exposed to the risk of physical complications of reflux, or in whom reflux causes significant impairment of health related well-being or QoL, after adequate reassurance of the benign nature of their symptoms

Pathogenic Factors in GERD

• Esophageal
• Heartburn and Regurgitation
• Dysphagia and Odynophagia (stricture and severe esophagitis)
• Barrett’s esophagus
• Esophageal adenocarcinoma
• Noncardiac chest pain
• E.N.T Complications
• Sore Throat
• Hoarseness/Laryngitis
• Globus sensation
• Throat Clearing
• Chronic Otitis media and Sinusitis
• Dental erosions
• Laryngeal cancer
• Pulmonary complicationc
• Asthma
• Chronic dry cough
• Aspiration Pneumonia
• Bronchiectasis
• Pulmonary Fibrosis
•   Miscellaneous
• Dyspepsia (nausea, vomiting, abdominal Pain)
• Anorexia, Wt. Loss
• Anemia, Fatigue
• Hiccups
• Burning Mouth
• Sleep disturbances

Clinical Manifestations of GERD

Indications for diagnostic testing in suspected GERD

• Uncertain diagnosis
• Atypical symptoms ( chest pain, ENT, Pulmonary)
• Symptoms associated with complications (dysphagia, odynophagia, unexplained weight loss, bleeding, anemia)
• Inadequate response to therapy
• Recurrent symptoms
• Prior to anti-reflux surgery

Diagnostic studies in GERD

• Diagnosis and Evaluation of GERD is based on Clinical Presentation and Diagnostic tests.There is no real gold standard, each test answers a part of the question:

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• Barium swallow: test of choice for evaluating DYSPHAGIA
• EGD: If there is any DAMAGE or COMPLICATION
• pH monitoring : if there is pathologic ACID REFLUX
• Manometry: If there is any FUCTIONAL MOTILITY ABNORMALITY predisposing to reflux, and before surgery
• Empiric trial of acid suppression a PRACTICAL approach

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• Intra luminal Electrical Impedance: if there is ANY REFLUX AND SYMPTOM CORRELATION

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NORMAL LES

GRADE I

GRADE III

INCOMPETENT LES

HIATUS HERNIA

GRADE II

GRADE IV

BARRETT’S

Endoscopy Findings in GERD

Gastroentrology; 98: A100, 1990

LOS ANGELES CLASSIFICATION OF MUCOSAL DAMAGE

• A- one or more mucosal break <5mm
• B- one or more mucosal break >5mm
• C- mucosal break contiguous between tops of 2 or more folds but involving <75% of esophageal circumference
• D- same as C but >75% of circumference

The goal of GERD management

• Symptom control

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• Improve patients’ health-related quality of life

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• Promote mucosal healing (pH>4>12-15 hrs/24h)

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• Prevent complications and symptom relapse

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Medical therapy for GERD

• Life style modification
• Antacids
• Antisecretory therapy
• -H2 Blockers
• -PPIs
• Promotility therapy

H₂-RA (standard dose)

H₂-RA (anti-reflux dose)

PPI

PPI

H₂-RA (anti-reflux dose)

H₂-RA (standard dose)

Step up

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Step down

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PPI Pharmacology and Optimal Dosing

• Short half life 0.5-2hr
• Incompletely absorbed, needs acidic environment
• Accumulate at the cannalicular surface of parietal cell
• Bound irreversibly to activated proton pumps
• Inhibits 70% of the active proton pumps

Pharmacodynamic effects of PPIs

• PPIs inhibit meal stimulated, night and day acid secretion
• Use before breakfast, if 2nd dose needed before dinner
• Takes several days to reach steady state, sooner with bid1st week
• Faster steady state in pts with corpus predominant HP gastritis

Johnson et al. Am J Gastroenterol 2000

Maintenance of Healing of Erosive Esophagitis� (n = 318)

esomeprazole 40 mg

placebo

esomeprazole 20 mg^†

esomeprazole 10 mg

*P < 0.001 vs placebo

% patients in remission

0

20

40

60

100

0

1

3

6

80

93*

29

Duration of treatment (months)

94*

57*

Hierarchy of PPI use

• PPI once daily, may substitute ppi,
• 40% failure
• PPI plus H2 RA at bed time
• PPIs bid or double the dose
• PPI bid plus H2RA at bed time
• PPI+ Prokinetics,diabetics or narcotic user
• PPI + TLESR reducer, Baclofen, DGER
• PPI+ pain modulators,Tricyclics, SSRIs, Trazadone, NCCP

TREATMENT GUIDELINES BASED ON EGD FINDINGS

• NERD treat with ppi till better, then use on demand or intermittent (except elderly)
• Erosive Esophagitis Rx till heals, and continue Rx
• Barrett’s esophagus Rx for good
• Peptic stricture dilate and Rx
• Extra-esophageal manifestations

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Side effects of PPIs

• Headache, nausea, abdominal pain, diarrhea
• Fundic gland polyps
• ? B12 and Iron malabsorption, concern, not proven
• Increased risk of gram negative pneumonia in ICU, odd ratio 1.8,
• Two fold increase in C-Difficile colitis ( hospitalized, children, on antibiotics, immune suppressed )
• Increased salmonella and campylobacter gastroenteritis
• Increased risk of bacterial infection (reduced PMN activity)
• Increased risk of hip fracture , odd ratio 2.0 (calcium malabsorption)
• PPIs induced interstitial nephritis
• Reduced thyroxine absorption

GERD in Elderly Patients

• GI tract changes with age:
• -Decrease normal peristalsis and increased nontransmitted and simultaneous contractions
• - Decrease saliva
• - increase prevalence of HH
• - Increase swallowing time due to decrease muscle mass
• - Multiple medications that lowers LESP
• - Use of NSAIDs
• Decline of severe heartburn in spite of severe GERD

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• Elderly pts >65 may present with anorexia, wt. loss , anemia, dysphagia,respiratory symptoms and chest pain.
• Incresed incidence of:
• - Erosive Esophagitis (37% in >70 vs 17% in <21)
• - Barrett’s Esophagus
• - Esophageal Adenocarcinoma
• EGD is indicated in all elderly pts with GERD symptoms

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• Long term PPI if heartburn, HH, and EE originally

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Omeprazole requirement in �GERD

• 65% omeprazole 20mg/d

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• 20% omeprazole 20mg bid

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• 21% Omeprazole 40mg bid

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Some reasons why PPIs may fail to control gastric acidity

• Compliance
• Improper dosing time, see if taken with food or antacid
• Weakly acidic reflux
• Bile reflux
• Nocturnal reflux
• Significant intersubject variability in bioavailability of PPIs which may be even further when taken with food
• Acid reducing effect of PPIs is reduced in Helicobacter pylori negative patients
• Acid Hypersecretors (rare)
• Rapid metabolizers of PPIs by cytochrome P-450 cyp 2c isoenzyme

Some reasons why PPIs may fail to control gastric acidity

• Incorrect diagnosis
• Eosinophilic esophagitis
• Visceral hypersensitivity
• Psychological comorbidity
• Drugs such as aspirin, NSAIDs and other drugs known to cause direct topical injury
• Factors including gastric stasis, ineffective peristalsis.
• Patients with GERD often have symptoms including bloating, distention,nausea which may be unmasked by PPI even though the classic reflux symptoms have improved

Impedance Technology Fundamentals

The Impedance Scale

Refluxate

Esophageal Lining

Food

Saliva

Air

Low Conductivity = High impedance

High Conductivity = Low impedance

Impedance

MultiChannel Intraluminal Impedance

(MII)

Impedance Technology Fundamentals

Swallow

Reflux

Impedance Technology Fundamentals

Impedance pH and Manometry

• Impedance determines refluxate presence, distribution, clearing time, liquid, gas or mixed

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• MII pH shows GER contents
• Acid reflux (pH<4.0)
• Non-acid reflux (pH>4.0 and up to 1 pH point drop)
• Minor acid reflux (pH>4.0 but 2 pH point drop)
• Acid re-reflux (pH <4.0 and may not change)

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• MII Manometry determines bolus transfer of liquids and solids

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Clinical indications of combined MII-pH testing

• Patients with persistent symptoms on bid, PPI therapy (refractory GERD, reason for GI referral)

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• Patients with ? GERD related ENT and Pulmonary symptoms

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• Patients with reflux symptoms and achlorhydria (I.e. atrophic
• gastritis)

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• Patients with reflux symptoms after surgical gastrectomy

Persistent heartburn on PPI

• In patients with persistent symptoms when on bid PPI Impedance pH studies reveals
• 20% have Acid reflux = drop in pH to < 4.0

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• 40% Non-Acid reflux = pH stays above 4.0
• and does not drop more than1 pH unit

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• 40% No Reflux preceding symptoms

Symptoms Not Correlated with Reflux

New formulation of PPI

• IR-OME, naked omeprazole+Na bicarb, eliminates meal timing, no need for food, good for on demand rx
• Kapidex 60mg, dual delayed release Lansoprazole
• Tenatoprazole 40 mg, half-life 9.3 hrs, like40 mg bid esomeprazole
• S-Tenatoprazole-Na (STU-Na) 60mg effect on nocturnal heartburn present 5 days after D/C in it
• AGN201,9047 600mg acid stable product of omeprazole producing continuous metered absorption
• K competetive acid blocker, AZD0865 rapid onset, bid
• GABA-B agonist Baclofen, reduces TLESR, reduces all refluxes, specially nonacid reflux
• XP19986 prodrug of R-Baclofen 40 mg dose
• 5-HT4receptor agonist Tegaserod, prokinetic and sensitivity modulator, 6mg bid

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Night time GERD

• Day and night GERD 65%, day only GERD 20% and night only GERD 13%
• Asthma, morning cough and phlegm is 2 to 3 times more common with nighttime GERD
• Predictors of nighttime gerd:
• Obesity (increased intragastric pressure, increase HH, dietary factors, ? Humoral factors), HTN (? Meds), Benzodiazepines ( lowers LESP), Carbonated beverages, Insomnia, Snoring, and sleeping during the day

GERD and Asthma

• Up to 70% of asthmatics complain of heartburn

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• Prevalence of GERD in asthmatics is 30% to 80%.
• GERD produces or exacerbate asthma by reflex and reflux
• Asthma conversely produces or aggravate GERD by :
• Flattening diaphragm
• Relaxing LES (Flattening diaphragm and albuterol inhalers dose dependant decrease in LESP and peristalsis amplitude, anticholinergics)
• Increasing acid exposure of distal and proximal esophagus high dose steroids for more than 7 days)
• HH, supine position and dietary factors more frequent in asthmatics

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• Pts with asthma>60 yo have 13x more chance of having GERD than healthy pts < 20 yo.
• EGD is normal in >60% of asthmatics

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