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Helicobacter pylori and
Peptic Ulcers
Omkar Potnis
Medical Technology
Department of Biotechnical and Clinical Laboratory Sciences
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Learning Objectives
On completion of this seminar, students will be able to:
Recognize the typical clinical presentation and risk factorsfor peptic ulcer disease
Understand pathophysiology of PUD focusing onH. pylori
Describe an appropriate diagnostic plan based on
individual risk factors
Prescribe an appropriate therapy
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Case Presentation
Mr. Jones, a 45 year old male presents to yourhospital with epigastric abdominal pain x 2 weeks.
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Case Symptoms
He describes it as a burning pain which is non-radiating andis worse after he eats.
He has frequent belching with bloating sensation but deniesnausea, vomiting, diarrhea, constipation, or weight loss.
He has tried rolaids (antacids) which do help a little.
Which symptoms support the possible diagnosis of PUD?
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Signs and Symptoms of PUD
Epigastric pain is most common symptom
Pain described as gnawing or burning
May radiate to the back
Occurs 1-3 hours after meals or at night
Relieved by food, antacids or vomiting
Dyspepsia including belching/ bloating
Hematemesis or melena with GI bleeding
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Duodenal and Gastric Ulcers
http://www.medicinenet.com/peptic_ulcer/
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Aggressive Factors Acid/Pepsin
H. pyloriinfection
NSAIDs
Smoking
Defensive Factors Mucus-bicarbonate barrier
Barrier of apical membrane
Mucosal blood flow
Prostaglandins
Epithelial cell restitution
Defensive
Factors
Aggressive
Factors I II
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Risk Factors
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A silver stain ofH. pylori on gastric mucus-secreting
epithelial cells (x1000).
From Dr. Marshall's stomach biopsy taken 8 days
after he drank a culture of H. pylori (1985).
H.pylori
Robbins and Cotran PATHOLOGIC BASIS OF DISEASE, 7th Edi t ion
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Helicobacter Pylori
Most common cause of PUD
Gram negative
Spiral shaped
Microaerophilic
Corkscrew motility by 4-6polar flagella.
Unable to ferment or oxidizecarbohydrates
Slow-growing
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(Bulletin of the World Health Organization, 2001, 79: 455460)
Epidemiology
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Mode of transmission
Humans are principal reservoir
Possible environmental reservoirs include contaminatedwater sources.
Oral-oral- Saliva or vomit
Fecal-oral
- Water contaminated with human wastes- Factors linked to poor hygiene
Iatrogenic and Occupational- Contaminated endoscopes or pH probes
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Location of the H.pylori
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Virulence Factors
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Robbins and Cotran PATHOLOGIC BASIS OF DISEASE, 7th Edi t ion
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Disorders caused by H.pylori
H. pyloriis the cause of most cases of Peptic UlcerDisease (PUD) Increases risk of both duodenal and gastric ulcers
found in 90% of duodenal ulcers and 70% of gastriculcers
Lifetime risk of peptic ulcer in pt withH. pyloriis ~3%.
H. pyloriis a primary risk factor for gastric cancerand adenocarcinoma Categorized as a group I carcinogen
H. pyloriincreases risk of MALT lymphoma
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Typical endoscopic, endosonographic and histological pictures in
MALT-lymphomaRobbins and Cotran PATHOLOGIC BASIS OF DISEASE, 7th Edi t ion
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Epithelial cell proliferation is increased with gastricHelicobacter pylori infection
(a) an uninfected stomach tissue(b) thirty-six weeks post-infection withH. pylori
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Sequence of histological and endoscopic events inH. pylori infectedstomach
Transformation of chronic atrophic gastritis to chronic active gastritis
with polyp, intestinal metaplasia and dysplasia to cancer.
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Diagnosis
Invasive
tests
Non-invasive
tests
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Non-invasive
tests
Urea Breath test
C13 UBT
C14 UBTStool Tests
PCR
Detection of Ag
Detection ofAntibodies
Serum
Urine
Saliva
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Urea Breath Test
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Solution of labeled ureaingested by the patient
IfH. pylori is present inthe stomach
Solution is rapidly
hydrolyzed
Labeled CO2 is absorbedby the blood and exhaled
and detected in expired air.
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H. pyloristool antigen test (HpSA)
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Techniques :
Enzyme immunoassay
Immunochromatography
Detects active infection
Uses polyclonal anti-H.pyloriantibodies
Simple, inexpensive
HpSATM Immunocard kits.
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Serological Techniques Techniques :
Complement fixation test
Latex agglutination test
ELISA
Antigens used for diagnosis :
Urease and flagellar proteins
Several Virulence factors
Antibodies detected :
IgG is the predominant class even in children
IgM rarely observed
IgA elevated in majority of infected cases but not all
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Invasive
tests
Specimens
CultureUrease Molecular
Tests
Endoscopic biopsy
Gastric juice
Blood
Liver biopsy Rarely used
Microscopy
Bacteriology
Histopathology
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Endoscopy
Duodenal ulcer
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Molecular methods
PCR for detection ofH. pylori
PCR for detection of pathogenic factors
Genes involved in adherence
Genes involved in pathogenicity
Real Time PCR using SYBR green dye or
fluorescence resonance energy transfer (FRET)principle
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Histopathological diagnosis
Stains
Grams stain Giemsa stainWarthin silver starry stainHematoxylin & Eosin stain Acridine orange stain
Immunostaining (Dako,Denmark) Helicobacter py lor iobserved on a gastric biopsysmear after acridine orange staining.Magnification, x1,000
A silver stain (Warthin Starry) ofHelicobacterpylor i
on gastric mucus-secreting epithelial cells (x1000).
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3
2
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Growth on horse blood agar
E-test
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Urea in substrate pad reacts with urease
NH3
NH3 passes through the semi-porousmembrane
dark blue or purple color on the yellow pHpaper directly above anH. pylori-infected
biopsy
A piece of gastric mucosa is placed in a
small well.
The presence ofurease is an indicator ofthe presence ofH. pyloriand results in acolor change fromyellowtopink
Phenotypic Tests - Urease
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http://www.ganfyd.org/index.php?title=Ureasehttp://www.ganfyd.org/index.php?title=Urease -
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Mr. Jones Prior Ulcer History On further questioning, Mr. Jones states he had
similar abdominal pain three years ago and was
told by his physician at that time that it wasmost likely due to an ulcer.
He had no definitive diagnostic tests done at thattime.
What would you do at this time?
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Case Diagnosis Mr. Jones Upper GI series showed radiologic findings of
thickened fold within the stomach
Outpatient esophagogastroduodenoscopy (EGD)was performed
Biopsy of antral part of the stomach wasconsistent with moderate gastritis. No tumor was seen 3+ to 4+ of bacterial organism was found
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Case Study
Gastric biopsy photomicrograph from
J Natl Med Assoc. 2007 January; 99(1): 3134.
3
H. pylori
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Key Information Pointing to Diagnosis
Presence of bacterial organism
Evidence of moderate gastritis visualizedin biopsy
Past medical history of gastric ulcer
Symptoms of dyspepsia and abdominalpain
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Results Mr. Jones is suffering from Chronic gastritis
The causative organism isHelicobacter pylori
Confirmed by histopathologic examination ofbiopsy specimen
How do we treat the infection?
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PPI(H2blocker)
or
Bismuth
TwoAntibiotics+
ClarithromycinAmoxicillinTetracycline
MetronidazoleFurazolidone
Colloidal Bismuth
Subcitrate (CBS)
Treatment
Triple Therapy
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Future Development
Currently : Vaccine using urease and
HspB are on trial in animal models
Prevention Probiotics may prevent infection Reduction of risk factors such as poor
socioeconomic status Improving living conditions and hygiene
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Lets review.
Robbins and Cotran PATHOLOGIC BASIS OF DISEASE, 7th Edi t ion
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In Summary
H. pylori is the most common cause of PUD and is a risk factor forgastric cancer
Clean and hygienic living conditions help prevent infections
Transmission is via person to person
Threat is prevalent, about half of the worlds population is infected.
Severity of symptoms depend on region, age, and lifestyle.
Disease involves chronic gastritis, gastric and duodenal ulcers.
H. pyloriinfection increases risk of PUD, gastric CA, and MALTlymphoma
Typical symptoms are nausea, epigastric pain, vomiting, anorexia
Diagnostic tests include biopsy, urea breath test, histopathology etc.
Triple therapy for treatment
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ReferencesAlgood HMS, Cover TL.Helicobacter pylori persistence: an overview of interactions betweenH.
pylori and host immune defenses. Clin Microbiol Rev 2006;19:597-613.
Dunn BE, Cohen H, Blaser MJ.Helicobacter pylori. Clin Microbiol Rev 1997;10:720-41.
Kusters JG, van Vliet AHM, Kuipers EJ. Pathogenesis ofHelicobacter pylori infection. ClinMicrobiol Rev 2006;19:449-90.
Malfertheiner P, Megraud F, O'moraina C, Hungin APS, Jones R, Axon A et al. Current
concepts in the management ofHelicobacter pylori infection. The Maastricht 2-2000 ConsensusReport. Aliment Pharmacol Ther 2002;16:167-80.
Mgraud F, Lehours P.Helicobacter pylori detection and antimicrobial susceptibility testing.Clin Microbiol Rev 2007;20:280-322.
Polk DB, Peek RM Jr. Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer2010;10:40314.
Schmidt H, Hensel M. Pathogenicity islands in bacterial pathogenesis. Clin Microbiol Rev2004;17:14-56.
Singh V, Trikha B, Nain CK, Singh K, Vaiphei K. Epidemiology ofHelicobacter pylori and pepticulcer in India. J Gastroenterol Hepatol 2002;17:659-65.
Studies onHelicobacter pylori. National Institute of Cholera And Enteric Diseases (NICED)Annual Report 2004-2005.
Wroblewski LE, Peek RM Jr, Wilson KT.Helicobacter pylori and gastric cancer: factors thatmodulate disease risk. Clin Microbiol Rev 2010;23:713-39.
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Thank You !