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Helicobacter pylori and Peptic Ulcers


Omkar Potnis Medical Technology Department of Biotechnical and Clinical Laboratory Sciences

Learning Objectives
On completion of this seminar, students will be able to: Recognize the typical clinical presentation and risk factors for peptic ulcer disease

Understand pathophysiology of PUD focusing on H. pylori


Describe an appropriate diagnostic plan based on individual risk factors Prescribe an appropriate therapy

Case Presentation
Mr. Jones, a 45 year old male presents to your hospital with epigastric abdominal pain x 2 weeks.

Case Symptoms
He describes it as a burning pain which is non-radiating and is worse after he eats. He has frequent belching with bloating sensation but denies nausea, vomiting, diarrhea, constipation, or weight loss. He has tried rolaids (antacids) which do help a little.

Which symptoms support the possible diagnosis of PUD?

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

Duodenal and Gastric Ulcers

http://www.medicinenet.com/peptic_ulcer/

Risk Factors
Aggressive Factors
Acid/Pepsin H. pylori infection NSAIDs Smoking
I

Defensive Factors
Mucus-bicarbonate barrier Barrier of apical membrane Mucosal blood flow Prostaglandins Epithelial cell restitution

Aggressive Factors

Defensive Factors

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A silver stain of H. 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 Edition

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Helicobacter Pylori

Most common cause of PUD Gram negative Spiral shaped Microaerophilic Corkscrew motility by 4-6 polar flagella. Unable to ferment or oxidize carbohydrates Slow-growing

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Epidemiology

Areas with H. pylori

(Bulletin of the World Health Organization, 2001, 79: 455460)

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Mode of transmission
Humans are principal reservoir Possible environmental reservoirs include contaminated water 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 Edition

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Disorders caused by H.pylori


H. pylori is the cause of most cases of Peptic Ulcer Disease (PUD)
Increases risk of both duodenal and gastric ulcers found in 90% of duodenal ulcers and 70% of gastric ulcers Lifetime risk of peptic ulcer in pt with H. pylori is ~3%.

H. pylori is a primary risk factor for gastric cancer and adenocarcinoma


Categorized as a group I carcinogen

H. pylori increases risk of MALT lymphoma

Typical endoscopic, endosonographic and histological pictures in MALT-lymphoma


Robbins and Cotran PATHOLOGIC BASIS OF DISEASE, 7th Edition

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Epithelial cell proliferation is increased with gastric Helicobacter pylori infection

(a) an uninfected stomach tissue

(b) thirty-six weeks postinfection with H. pylori

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Sequence of histological and endoscopic events in H. pylori infected stomach 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 UBT

Stool Tests PCR Detection of Ag

Detection of Antibodies Serum Urine Saliva

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Urea Breath Test


Solution of labeled urea ingested by the patient

If H. pylori is present in the stomach


Solution is rapidly hydrolyzed Labeled CO2 is absorbed by the blood and exhaled and detected in expired air.

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H. pylori stool antigen test (HpSA)


Techniques : Enzyme immunoassay Immunochromatography Detects active infection Uses polyclonal pylori antibodies Simple, inexpensive
HpSATM Immunocard kits.

anti-H.

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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 Endoscopic biopsy Gastric juice Blood Rarely used Liver biopsy

Microscopy Bacteriology Histopathology

Culture

Urease

Molecular Tests

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Endoscopy

Duodenal ulcer

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Molecular methods
PCR for detection of H. 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 stain Warthin silver starry stain Hematoxylin & Eosin stain Acridine orange stain Immunostaining (Dako,Denmark)

Helicobacter pylori observed on a gastric biopsy smear after acridine orange staining. Magnification, x1,000

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A silver stain (Warthin Starry) of Helicobacter pylori on gastric mucus-secreting epithelial cells (x1000).

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E-test

Growth on horse blood agar

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Phenotypic Tests - Urease


A piece of gastric mucosa is placed in a small well.

The presence of urease is an indicator of the presence of H. pylori and results in a color change from yellow to pink Urea in substrate pad reacts with urease
NH3 NH3 passes through the semi-porous membrane dark blue or purple color on the yellow pH paper directly above an H. pylori-infected biopsy

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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 was most likely due to an ulcer. He had no definitive diagnostic tests done at that time. 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 was consistent with moderate gastritis.
No tumor was seen 3+ to 4+ of bacterial organism was found

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Case Study
H. pylori

Gastric biopsy photomicrograph from J Natl Med Assoc. 2007 January; 99(1): 3134.

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Key Information Pointing to Diagnosis


Presence of bacterial organism Evidence of moderate gastritis visualized in biopsy Past medical history of gastric ulcer Symptoms of dyspepsia and abdominal pain

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Results
Mr. Jones is suffering from Chronic gastritis The causative organism is Helicobacter pylori Confirmed by histopathologic examination of biopsy specimen

How do we treat the infection?

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Treatment
PPI (H2 blocker) or Bismuth
Colloidal Bismuth Subcitrate (CBS)

Two Antibiotics
Clarithromycin Amoxicillin Tetracycline Metronidazole Furazolidone

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 Edition

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In Summary
H. pylori is the most common cause of PUD and is a risk factor for gastric 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. pylori infection increases risk of PUD, gastric CA, and MALT lymphoma 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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References
Algood HMS, Cover TL. Helicobacter pylori persistence: an overview of interactions between H. 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 of Helicobacter pylori infection. Clin Microbiol 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 of Helicobacter pylori infection. The Maastricht 2-2000 Consensus Report. 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 Cancer 2010;10:40314. Schmidt H, Hensel M. Pathogenicity islands in bacterial pathogenesis. Clin Microbiol Rev 2004;17:14-56. Singh V, Trikha B, Nain CK, Singh K, Vaiphei K. Epidemiology of Helicobacter pylori and peptic ulcer in India. J Gastroenterol Hepatol 2002;17:659-65. Studies on Helicobacter 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 that modulate disease risk. Clin Microbiol Rev 2010;23:713-39.

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Thank You !

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