Helicobacter Pylori Or Campylobacter Pyloridis

Blossom Sabi 10/3/2012 SYSU

Definition

Helicobacter pylori colonizes the stomach of 50% of the world's human population throughout their lifetimes. Colonization with this organism is the main risk factor for peptic ulceration as well as for gastric adenocarcinoma and gastric MALT lymphoma.

• It contains a hydrogenase which can be used to obtain energy by oxidizing molecular hydrogen (H2) produced by intestinal bacteria.It produces oxidase, catalase, and urease.

• H. pylori possesses five major outer membrane protein (OMP) families.

1. putative adhesins. 2. porins.3. iron transporters.4. flagellum-associated proteins 5. proteins of unknown function.

The genome of the strain "26695" consists of about 1.7 million base pairs, with some 1,550 genes.

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The cagA gene codes for one of the major H. pylori virulence proteins. Bacterial strains that have the cagA gene are associated with an ability to cause ulcers.

Winners of 2005 Nobel prize for physiology and medicine

Winners of 2005 Nobel prize for physiology and medicine

Etiologic Agent

H. pylori is a gram-negative bacillus that has naturally colonized humans for at least 50,000 years—and probably throughout human evolution.

It lives in gastric mucus, with a small proportion of the bacteria adherent to the mucosa and possibly a very small number of the organisms entering cells or penetrating the mucosa; its distribution is never systemic. Its spiral shape and flagella render H. pylori motile in the mucus environment.

The organism has several acid-resistance mechanisms, most notably a highly expressed urease that catalyzes urea hydrolysis to produce buffering ammonia. H. pylori is microaerophilic (requiring low levels of oxygen), is slow-growing, and requires complex growth media in vitro.

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Preval ence i ndevel oped countri es

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Prevalence of H.Pylori in developed AND developed countries

H.Pylori Infection Prevalence Varies with Age In Developed Country

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# Strains producing cag pathogenicity DNA island) are more likely to give rise to severe gastritis, peptic ulceration and gastric cancer than strains without it.

DNA island or cag pathogenicity island is a large region of DNA which has genes that control production of toxins.

Vacuolating toxin (VaC A)Cytotoxin ( cytotoxin associated gene Cag- A)

# Humans are the only important reservoir of H. pylori and acquisition in adulthood is uncommon.

# Whether transmission takes place more often by the fecal-oral or the oral-oral route is unknown, but H. pylori is easily cultured from vomitus and gastroesophageal refluxate and is less easily cultured from stool.

Diagrammatic representation of the oxyntic gastric gland

Gastric parietal cell undergoing transformation after secretagogue-mediated stimulation. cAMP, cyclic adenosine monophosphate.

GASTRODUODENAL MUCOSAL DEFENSE

Bacterial factors

H. pylori is able to facilitate gastric residence, induce mucosal injury, and avoid host defense.

A specific region of the bacterial genome, the pathogenicity island (cag-PAI), encodes the virulence factors Cag A and pic B.

Vac A targets human CD4 T cells, inhibiting their proliferation and in addition can disrupt normal function of B cells, CD8 T cells, macrophages and mast cells.

Multiple studies have demonstrated that H. pylori strains that are cag-PAI positive are associated with a higher risk of peptic ulcer disease, premalignant gastric lesions and gastric cancer than are strains that lack the cag-PAI.

Urease, which allows the bacteria to reside in the acidic stomach, generates NH3, which can damage epithelial cells.

Host factors

The inflammatory response to H. pylori includes recruitment of neutrophils, lymphocytes (T and B), macrophages, and plasma cells.

The pathogen leads to local injury by binding to class II major histocompatability complex (MHC) molecules expressed on gastric epithelial cells, leading to cell death (apoptosis).

Bacterial strains that encode cag-PAI can introduce Cag A into the host cells, leading to further cell injury and activation of cellular pathways involved in cytokine production.

Elevated concentrations of multiple cytokines are found in the gastric epithelium of H. pylori–infected individuals, including interleukin (IL) 1/, IL-2, IL-6, IL-8, tumor necrosis factor (TNF) , and interferon (IFN-).

Although lipopolysaccharide (LPS) of gram-negative bacteria often plays an important role in the infection, H. pylori LPS has low immunologic activity compared to that of other organisms. It may promote a smoldering chronic inflammation.

cause epithelial cell injury include (1) activated neutrophil-mediated production of reactive oxygen or nitrogen species and enhanced epithelial cell turnover and (2) apoptosis related to interaction with T cells (T helper 1, or TH1, cells) and IFN-.

Outline of the bacterial and host factors important in determining H. pylori–induced gastrointestinal disease. MALT, mucosal-associated lymphoid tissue.

Natural history of H. pylori-infection

Antral predominant

gastritis

•Duodenal ulcer

Corpus predominant

atropic gastritis

•Gastric ulcer •Gastric Adenocarcinoma

Non atropic pangastritis

•MALT Lymphoma

Differnece between Gastric Ulcer and Duodenal Ulcer

DUODENAL ULCER GASTRIC ULCER

Epidemiology:Worldwide, >80% are related to H. pylori colonization.

>60% of gastric ulcers are related to H. Pylori colonization.

Pathology:1st part of the duodenum (>95%), with ~90% located within 3 cm of the pylorus. They are usually 1 cm in diameter but can occasionally reach 3–6 cm (giant ulcer). Ulcers are sharply demarcated, with depth at times reaching the muscularis propria.

In contrast GUs can represent a malignancy and should be biopsied upon discovery. Benign GUs are most often found distal to the junction between the antrum and the acid secretory mucosa..

The base of the ulcer often consists of a zone of eosinophilic necrosis with surrounding fibrosis. Malignant DUs are extremely rare.

Benign GUs are quite rare in the gastric fundus and are histologically similar to DUs. Benign GUs associated with H. pylori are also associated with antral gastritis.

Pathophysiology:

H. pylori and NSAID-induced injury account for the majority of DUs.

GUs that occur in the prepyloric area or those in the body associated with a DU or a duodenal scar are similar in pathogenesis to DUs.

Of these, average basal and nocturnal gastric acid secretion appears to be increased in DU patients as compared to controls.

Gastric acid output (basal and stimulated) tends to be normal or decreased in GU patients.

Chronic duodenal ulcer usually occurs in the 1st part of the duodenum just distal to the junction of pyloric and duodenal mucosa; 50% are on the anterior wall.

The male to female ratio for duodenal ulcer varies from 5:1 to 2:1,

Blood group: O

Chronic gastric ulcer is usually single; 90% are situated on the lesser curve within the antrum or at the junction between body and antral mucosa.

gastric ulcer is 2:1 or less.

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Common feature Complication : Bleeding Posterior > Anterior Gastroduodenal artery ( UGIE+Cauterization)

Perforation: Anterior>Posterior Fluid in greater sac.Gastric outlet obstruction: metabilc alkalosis.Pain 2hour relieved by food epigastric painHunger pain causes obesity Rx: UGIE+CAUTERIZATION

Gastric and duodenal ulcers coexist in 10% of patients and more than one peptic ulcer is found in 10-15% of patients.

Bleeding : Gastric ArteryPenetration occur gradually slowly …Posterior : develop pseudopancreatic cyst, Pancreatits.Anterior : transverse colon causes fecal fistula. Laterally : liver cirrhosis.Perforation :Fluid in lesser sac.Malignancy : Gastric outlet obstructionmetabilc alkalosisPain <1/2 causes epigastric painRx: Fluid resusciation

A chronic ulcer extends to below the muscularis mucosae and the histology shows four layers: surface debris, an infiltrate of neutrophils, granulation tissue and collagen.

GASTRIC CARCINOMA

There is marked geographical variation in incidence. It is extremely common in China, Japan and parts of South America (mortality rate 30-40 per 100 000), less common in the UK (12-13 deaths per 100 000) and uncommon in the USA. Studies of Japanese migrants to the USA have revealed a much lower incidence in second-generation migrants, confirming the importance of environmental factors. Gastric cancer is more common in men and the incidence rises sharply after 50 years of age.

Aetiology of GC

H. pylori is associated with chronic atrophic gastritis and gastric cancer . H. pylori infection may be responsible for 60-70% of cases and acquisition of infection at an early age may be important.

Although the majority of H. pylori-infected individuals have normal or increased acid secretion, a few become hypo- or achlorhydric and these people are thought to be at greatest risk.

Chronic inflammation with generation of reactive oxygen species and depletion of the normally abundant antioxidant ascorbic acid are also important.

• Primary gastric lymphoma accounts for less than 5% of all gastric malignancies. The stomach is, however, the most common site for extranodal non-Hodgkin's lymphoma and 60% of all primary gastrointestinal lymphomas occur at this site.

• Lymphoid tissue is not found in the normal stomach but lymphoid aggregates develop in the presence of H. pylori infection. Indeed, H. pylori infection is closely associated with the development of a low-grade lymphoma ('MALToma').

Gastric lymphoma

Methods for the diagnosis of Helicobacter Pylori infection

Invasive

1. Endoscopy based Biopsy Urease testHere specimen from antral biopsy are tested for “urease”.It is most convenient endoscopy based test.It is quick and simple however it is neither fully sensitive nor fully specific.2. Histology :Here the biopsy specimen is subjected to histological examination,It is accurate, but time consuming.3. Culture:Here the biopsy specimen put in a culture medium.This is accurate and permits determination of antibiotic susceptiblities, but is also time consuming

Non Invasive

1. Urea Breath tests: Here patient drinks a labelled urea

solution and blows into a tube. If H.Pylori urease is present, the

urea is hydrolysed and labelled co2 is detected in breath samples.

It is thus a simple, safe test and cheaper than endoscopy.

2. Serological : Here specific IgG lelvels in serum

are assessed. Does not differentiate between

active and remote infection. Nevertheless it is particularly suited

as an epidemiological tool.3. Stool antigen test: New test appears less accurate than

urea breath test. Useful for follow up after treatment.

Diagnosis

Invasive tests:

Endoscopy often is not performed in the initial management of young dyspeptic patients without "alarm" symptoms but is commonly used to exclude malignancy in older patients.

If endoscopy is performed, the most convenient biopsy-based test is the biopsy urease test, in which one large or two small antral biopsy specimens are placed into a gel containing urea and an indicator. The presence of H. pylori urease leads to a pH alteration and therefore to a color change, which often occurs within minutes but can require up to 24 h.

Histologic examination of biopsy specimens for H. pylori also is accurate, provided that a special stain (e.g., a modified Giemsa or silver stain) permitting optimal visualization of the organism is used.

Noninvasive Tests:

H. pylori testing is the norm if gastric cancer does not need to be excluded by endoscopy. The most consistently accurate test is the urea breath test.

In this simple test, the patient drinks a solution of urea labeled with the nonradioactive isotope 13C and then blows into a tube. If H. pylori urease is present, the urea is hydrolyzed and labeled carbon dioxide is detected in breath samples.

The stool antigen test.

The simplest tests for ascertaining H. pylori status are serologic assays measuring specific IgG levels in serum by enzyme-linked immunosorbent assay or immunoblot.—do not perform well.

H&E ×25.

Hematoxylin and eosin; magnification, ×100.

Pathology of Gastritis and Peptic Ulceration

Indications of treatment :

H. Pylori related duodenal and gastric ulceration Low garde B cell MALT lymphoma

Resectable tumours

• Complete surgical removal of the tumor with resection of adjacent lymph nodes offers the only chance for cure. However, this is possible in less than a third of patients.

• A subtotal gastrectomy is the treatment of choice for patients with distal carcinomas. The inclusion of extended lymph node dissection in these procedures appears to confer an added risk for complications without enhancing survival.

Unresectable tumours

• The management of inoperable, locally advanced cancer is unsatisfactory. • Modest palliation of symptoms can be achieved in some patients with chemotherapy

using FAM (5-fluorouracil, doxorubicin and mitomycin C) or ECF (epirubicin, cisplatin and 5-fluorouracil).

• Endoscopic laser ablation of tumour tissue for control of dysphagia or recurrent bleeding benefits some patients.

TREATMENT FOR GASTRIC ADENOCARCINOMA

Treatment of Gastric Lymphoma

Superficial MALTomas may be cured by H. pylori eradication.

The clinical presentation is similar to that of gastric cancer and endoscopically the tumour appears as a polypoid or ulcerating mass.

While initial treatment of low-grade MALTomas consists of H. pylori eradication and close observation, high-grade B-cell lymphomas are treated by a combination of chemotherapy, surgery and radiotherapy.

Assessing success of treatment/eradication of H.pylori

Non invasive test are preferred UREA BREATH TEST:

Test of chioce for documenting

eradication. STOOL ANTIGEN TEST:

If UBT is not available a stool antigen test should be considered for documenting eradication.

SEROLOGICAL TESTING: Is not useful for purpose of documentation of eradication as antibody titres fall slowly and often do not become undetectable.

Invasive tests are not preferred

BIOPSY BASED TESTS

(Biopsy Urease Test,Histology/culture)

are invasive tests based on Endoscopic biosy.

These may be used to document eradication but are not preferred for this purpose.