Helicobacter PyloriRelated gastroenterology
Prepared & Presented By:
Dr.Usman ul Haq
BEMS,RMP,UOP,
,
HELICOBACTER PYLORI
Background
Human stomach long considered inhospitable for bacteria.
Spiral shaped organisms occasionally visualized in
gastric mucous layer, but no evidence of disease association.
Organism classified first as Campylobacter pylori And
Now Helicobacter pylori. Other species of Helicobacter isolated from stomach,
intestine of other animals. Marshall and Warren culture organism from human
gastric mucosa and show association with gastric inflammation.
Helicobacter pylori
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).
MORPHOLOGY
Gram negativeSpiral rod FlagellatedMicroaerophilic
H. Pylori BacteriaUrease positive*Present in gastric
antrumProliferates in
mucus overlying gastric type mucosa
Not cleared by host immune response
*Scanning microscopic view of H. pylori
TRANSMISSION Humans are major - if not only - reservoir Transmission believed to be by fecal-oral
route. Organism can be cultured from feces. Family members often carry same strain Prevalence of infection likely related to
inferior hygienic conditions and poor sanitation.
Infection from environment or from animals cannot be totally excluded.
EPIDEMIOLOGY 1. Gastric colonization rate in developing countries is
about 80%
2. Gastric colonization rate in US and other developed
countries is about 30%
3. Prevalence of infection increases with age Age 10 = ~5% Age 30 = ~ 25% Age 60 = ~ 50% 4. In US, prevalence rates are higher in African-
Americans and Hispanics Age and low income = main risk factors for H. pylori infection
H. pylori Infection Risk Factors
Low socioeconomic status Crowded or unsanitary living conditions Born in a developing country Exposure to gastric contents
– Nurses
– Endoscopists
PATHOGENESIS
Colonization
Most bacteria killed in hostile environment of gastric lumen.
H. pylori proliferates in mucus layer over epithelium and is not cleared by host immune response.
H. pylori survives and grows there because of a variety of virulence factors that contribute to gastric inflammation, alter gastric acid production, and cause tissue destruction.
VIRULENCE FACTORS Initial colonization facilitated by:
Acid inhibitory protein - blocks acid secretion from parietal cells during acute infection
Urease - neutralizes gastric acids due to ammonia production. [also stimulates monocytes and neutrophils chemotaxis; stimulates production of inflammatory cytokines]
Heat shock protein: Enhances urease expression; co-expressed with urease on bacterial surface
Flagella - allows penetration into gastric mucous layer and help in movement.
Adhesins - mediate binding to host cells
Localized tissue damage mediated by:
Mucinases and phospholipases - disrupt gastric mucus
Vacuolating cytotoxin - induces vacuolation in epithelial cells that results in epithelial cell damage
All these factors plus LPS stimulate inflammatory response
Catalase - prevent from phagocytosis and intracellular killing
Plus other poorly defined factors that stimulate
IL-8 secretion by epithelial cells, that induce nitric oxide synthase which mediates tissue injury, and that induce programmed death of gastric epithelial cells.
Cag pathogenicity island - includes genes that confer enhanced pathogenicity, in part by inducing epithelial cells to produce inflammatory cytokines.
Pathogenesis of H. pylori infection The Flagellae make
it motile, allowing it
to live deep beneath
the mucosal layer.
It uses an adhesin
molecule(BabA) to
bind to epithelial
cells Where the pH
there is close to
neutral
Any acidity is buffered Any acidity is buffered by the organism's by the organism's production of the production of the enzyme urease, enzyme urease, which catalyzes the which catalyzes the production of production of ammonia (NH3) from ammonia (NH3) from urea & raises the pH urea & raises the pH there.there.
The bacterium The bacterium stimulates chronic stimulates chronic gastritis by provoking gastritis by provoking a local a local proinflammatory proinflammatory response.response.
In the cellular level: H. pylori express
cagA & vacA genes cagA gene
signals to the epithelial cells involving: - Cell replication, - Apoptosis, & - Morphological changes.
In the cellular level:In the cellular level: vacAvacA gene gene
producing a producing a pore-forming protein, pore-forming protein, which has many which has many destructing effect to destructing effect to the epithelium like: the epithelium like: --↑Cell ↑Cell permeability & efflux permeability & efflux of micronutrients, of micronutrients, -- Induction of Induction of apoptosis, & apoptosis, & - - Suppression of local Suppression of local cell immunitycell immunity
H.pylori as a cause of PUD
DU
GU
Studies show that about 95% of patients with DU
& 85% with GU are infected with H. pylori
95%85%
Evidence supporting H. pylori as major cause of peptic ulcer disease
H. pylori is found in almost all cases of PUD, (80%)while the use of NSAIDs (20%) .
When H. pylori is treated and eradicated, the rate
of ulcer recurrence is dramatically reduced.
H. pylori induced changes in acid secretion and mucosal resistance provide a plausible path physiologic explanation.
Pathogenesis of H. pylori infection
- ↓ Somatostatin production from antral D-cells due to antral gastritis- Low somatostatin will ↑Gastrin release from G-cell hypergastrinemia- This will stimulate acid production by the parietal cells leading to further duodenal ulceration.
Effects of H. pylori on gastric Hormones
This effect is exaggerated among smokers!
H Pylori Disease Associations other than GIT Migraine Headache Glaucoma Stroke Morning Sickness
Outcomes of H.Pylori Infection
Nearly all H. pylori colonized persons have gastric inflammation - but this - by itself is asymptomatic.
Symptoms are due to illness - such as peptic ulceration or gastric malignancy.
Develop in <10% individuals colonized with H. pylori.
Outcomes of H. pylori Infection
Often asymptomatic (latent), but not benign, with progressive gastric damage1
Dyspepsia Gastritis
Gastric tumors
PUD2: duodenal and gastric ulcers (17%)– Life-threatening complications occur in 1%-2% of
patients with peptic ulcer disease per year Gastric cancer3
Mucosa-associated lymphoid tissue (MALT)/primary gastric B-cell lymphoma3
Outcomes of H. pylori Infection
Latest research suggests ~45% of babies with Colic have H.
pylori. Eradication of H. pylori in Glaucoma
improved eyesight significantly. H. pylori is involved in some cardiac
conditions.
Natural History of Helicobacter pylori Infection
H. pylori Infection
The bad news High morbidity
– Chronic and acute gastritis– Peptic ulcers– Gastric cancer
Classified by WHO as a Class I carcinogen
H. pylori Infection
The best news is: It is curable
Indications for H. pylori testing
Dyspepsia in primary care setting. Documented gastric and duodenal ulcer. History of peptic ulcer. Gastric Mucosa-Associated Lymphoma. After resection of early gastric
adenocarcinoma. First-degree relative of a patient with gastric
cancer.
Problems with CurrentManagement of Dyspepsia
Many patients with dyspepsia are infected with H. pylori .
PPIs mask the symptoms of H. pylori ; they do not cure the underlying disease.
Cure reduces healthcare costs by avoiding further morbidity and mortality.
– 90% of patients with PUD do not experience a recurrence after H. pylori eradication
Current Trends in Management of Dyspepsia
Undifferentiated dyspepsia
Empiric trial of H2 blocker or
Proton Pump Inhibitor (PPI)
Symptoms persist?Yes
Test for H. pyloriPositive
Eradicationtherapy
Negative
GI referralor long-termPPI therapy
Recommended Management of Dyspepsia
Undifferentiated dyspepsia
Empiric trial of H2 blocker or
Proton Pump Inhibitor (PPI)
Symptoms persist?
Yes
Test for H. pyloriPositive
Eradicationtherapy
Negative
GI referralor long-termPPI therapy
No Routine follow-up
Diagnosis of H. pylori
Non-invasive C13 or C14 Urea Breath Test Stool antigen test H. pylori IgG titer (serology)
Invasive Gastric mucosal biopsy Rapid Urease test
Indications for Noninvasive Testing for H. pylori *
Strongly Recommended– Dyspepsia– History of/active peptic ulcer disease– Gastric MALT lymphoma– Following gastric cancer resection– Following peptic ulcer surgery– First-degree relative with gastric cancer– Long-term Non-steroidal anti-inflamatory
drugs (NSAID) therapy
Indications Noninvasive Testing for H. pylori *(cont.)
Advisable– Family history of duodenal ulcer
– Family members with H. pylori infection
– GERD requiring long-term PPI therapy
Diagnosis of H. pylori
Non-invasive 1. C13 or C14 Urea Breath Test
The best test for the detection
of an active infection
Diagnosis of H. pylori
Invasive Upper GI endoscopy
– Highly sensitive test– Patient needs sedation– Has both diagnostic & therapeutic role
Diagnosis of H. pylori
Invasive (endoscopy)– Diagnostic:
– Detect the site and the size of the ulcer, even small and superficial ulcer can be detected
– Detect source of bleeding– Biopsies can be taken for rapid urease test,
histopathology & culture
Diagnosis of H. pylori
Invasive (endoscopy) Rapid urease test ( RUT)
o Considered the endoscopic diagnostic test of choice
o Gastric biopsy specimens are placed in the rapid urease test kit. If H pylori are present, bacterial urease converts urea to ammonia, which changes pH and produces a CCOOLLOORR change
Diagnosis of H. pylori
Invasive (endoscopy)* Histopathology
o Done if the rapid urease test result is negative
* Cultureo Used in research studies and is not available
routinely for clinical use
H. Pylori: Gastric biopsy
H & E stain H. pylori immunostain
Diagnostic Tests for Helicobacter pyloriInvasive
Test Sensitivity (%)
Specificity (%)
Usefulness
Endoscopy with biopsy
Diagnostic strategy of choice in children with persistent or severe upper abdominal symptoms
Histology > 95 100 Sensitivity reduced by PPIs, antibiotics, & bismuth-containing compounds
Urease activity 93 to 97 > 95 Sensitivity reduced by PPIs, antibiotics, bismuth-containing compounds, & active bleeding
Culture 70 to 80 100 Technically demanding
Diagnostic Tests for Helicobacter pylori Noninvasive
Test Sensitivity (%)
Specificity (%)
Usefulness
Serology for IgG 85 79 Sensitivity & specificity vary widely; positive result may persist for months after eradication.
Reliability in children not adequately validated; not recommended
Diagnostic Tests for Helicobacter pylori Noninvasive
Test Sensitivity (%)
Specificity (%)
Usefulness
Urea breath test 95 to 100 91 to 98 Requires separate appointments; sensitivity reduced by PPIs, antibiotics, & bismuth-containing compounds; reliable test for cure.
Best available noninvasive test in children but higher false +ve rates in infants & children younger than six years compared with school-age children & adolescents
Diagnostic Tests for Helicobacter pylori Noninvasive
Test Sensitivity (%)
Specificity (%)
Usefulness
H. pylori stool antigen
91 to 98 94 to 99 Test for cure 7 days after therapy is accurate; sensitivity reduced by PPIs, antibiotics, & bismuth-containing compounds.
Easy to perform independent of age; possible alternative to urea test; monoclonal antibody-based test most reliable
Why Test Patients with GERD?
Reflux symptoms have been shown to improve when H. pylori is eradicated.
Patients with GERD and H. pylori infection experience decreased frequency of hospital visits and use of antiacid medications when H. pylori is eradicated-
Suggested Guidelines forTreatment of Patients with GI or Ulcer Disease
History & Physical Exam
Peptic ulcerdisease
Undifferentiateddyspepsia
Symptomsof GERD
Use of NSAIDsor aspirin
Positive
Eradicationtherapy
Confirmation of cure
Test for H. pylori
Suggested Guidelines forTreatment of Patients with GI or Ulcer Disease
History & Physical Exam
Peptic ulcerdisease
Undifferentiateddyspepsia
Symptomsof GERD
Use of NSAIDsor aspirin
Positive
Eradicationtherapy
Confirmation of cure
Negative
Treat for PUD,Initiate PPI therapy,
or discontinue NSAIDs
Test for H. pylori
.
Confirmation of Cure ofH. pylori Infection
Active tests must be used
–Cannot use serology Risks of not testing
–Recurrent ulcer
–Ulcer complications, gastric cancer
–Transmission to others
Conclusions
H. pylori is a transmissible, infectious disease with potentially serious outcomes.
H. pylori infection may be asymptomatic or cause dyspepsia.
Eradication therapy can cure H. pylori infection and prevent morbidity and downstream events such as PUD and gastric cancer.
Patients with symptoms of upper-GI disease, and who use aspirin or NSAIDs should be tested for H. pylori infection.
Conclusions (cont.)
Several noninvasive tests to detect H. pylori infection are available.– Categorized as detecting active infection or
identifying the presence of antibodies against H. pylori
Active tests of infection are required for post-treatment confirmation of cure of H. pylori infection
H. pyloriH. pylori
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