1. Helicobacter Pylori
Or
Campylobacter Pyloridis
Blossom Sabi
10/3/2012 SYSU

2. 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.

3. • 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.

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

5. Winners of 2005 Nobel prize
for physiology and medicine

6. Winners of 2005 Nobel prize
for physiology and medicine

7. 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.

8. Prevalence of H.Pylori in developed AND developed countries
80%
70%
60%
Pr eval ence i n
50% devel oped count r i es
40%
Pr eval ence i n
30% devel opi ng
count i r es
20%
10%
0%

9. H.Pylori Infection Prevalence Varies with Age In Developed Country
50%
45%
40%
35% 60- year - ol d per son
30%
30- year - ol d per son
25%
20% 3- 20 year ol d
15% per son
10%
5%
0%

10. # 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.

11. Diagrammatic representation of the oxyntic gastric gland

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

13. GASTRODUODENAL MUCOSAL DEFENSE

14. Bacterial factors Host factors
 H. pylori is able to facilitate gastric  The inflammatory response to H. pylori
residence, induce mucosal injury, and includes recruitment of neutrophils,
avoid host defense.
lymphocytes (T and B), macrophages,
 A specific region of the bacterial and plasma cells.
genome, the pathogenicity island (cag-  The pathogen leads to local injury by
PAI), encodes the virulence factors binding to class II major
Cag A and pic B. histocompatability complex (MHC)
molecules expressed on gastric
 Vac A targets human CD4 T cells, epithelial cells, leading to cell death
inhibiting their proliferation and in
addition can disrupt normal function of (apoptosis).
B cells, CD8 T cells, macrophages and  Bacterial strains that encode cag-
mast cells. PAI can introduce Cag A into the
host cells, leading to further cell injury
 Multiple studies have demonstrated and activation of cellular pathways
that H. pylori strains that are cag-PAI
positive are associated with a higher involved in cytokine production.
risk of peptic ulcer disease,  Elevated concentrations of multiple
premalignant gastric lesions and cytokines are found in the gastric
gastric cancer than are strains that
lack the cag-PAI. epithelium of H. pylori–infected
individuals, including interleukin (IL)
 Urease, which allows the bacteria to 1/, IL-2, IL-6, IL-8, tumor necrosis
reside in the acidic stomach, factor (TNF) , and interferon (IFN-).
generates NH3, which can damage
epithelial cells.

15.  Although lipopolysaccharide (LPS) cause epithelial cell injury include (1)
of gram-negative bacteria often activated neutrophil-mediated
plays an important role in the production of reactive oxygen or
infection, H. pylori LPS has low nitrogen species and enhanced
immunologic activity compared to epithelial cell turnover and (2)
that of other organisms. It may apoptosis related to interaction with T
promote a smoldering chronic cells (T helper 1, or TH1, cells) and
inflammation. IFN-.

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

18. Natural history of H. pylori-infection

19. Antral Corpus
Non atropic
predominant predominant
pangastritis
gastritis atropic gastritis
• Duodenal ulcer • Gastric ulcer • MALT
• Gastric Lymphoma
Adenocarcinoma

22. Differnece between Gastric Ulcer and Duodenal Ulcer
DUODENAL ULCER GASTRIC ULCER
Epidemiology:
Worldwide, >80% are related to H. >60% of gastric ulcers are related to
pylori colonization. H. Pylori colonization.
Pathology:
1st part of the duodenum (>95%), with In contrast GUs can represent a
~90% located within 3 cm of the malignancy and should be biopsied
pylorus. They are usually 1 cm in upon discovery. Benign GUs are most
diameter but can occasionally reach often found distal to the junction
3–6 cm (giant ulcer). Ulcers are between the antrum and the acid
sharply demarcated, with depth at secretory mucosa..
times reaching the muscularis propria.
The base of the ulcer often consists of Benign GUs are quite rare in the
a zone of eosinophilic necrosis with gastric fundus and are histologically
surrounding fibrosis. Malignant DUs similar to DUs. Benign GUs
are extremely rare. associated with H. pylori are also
associated with antral gastritis.

23. Pathophysiology:
GUs that occur in the prepyloric area or
H. pylori and NSAID-induced injury those in the body associated with a DU or
account for the majority of DUs. a duodenal scar are similar in
pathogenesis to DUs.
Of these, average basal and nocturnal Gastric acid output (basal and stimulated)
gastric acid secretion appears to be tends to be normal or decreased in GU
increased in DU patients as compared to patients.
controls.
Chronic duodenal ulcer usually occurs in Chronic gastric ulcer is usually single; 90%
the 1st part of the duodenum just distal to are situated on the lesser curve within the
the junction of pyloric and duodenal antrum or at the junction between body
mucosa; 50% are on the anterior wall. and antral mucosa.
The male to female ratio for duodenal ulcer gastric ulcer is 2:1 or less.
varies from 5:1 to 2:1,
Blood group: O A

24. Common feature Bleeding : Gastric Artery
Complication : Penetration occur gradually slowly …
Bleeding Posterior : develop pseudopancreatic
Posterior > Anterior cyst, Pancreatits.
Gastroduodenal artery
( UGIE+Cauterization) Anterior : transverse colon causes fecal
fistula.
Perforation: Anterior>Posterior Laterally : liver cirrhosis.
 Fluid in greater sac. Perforation :
Gastric outlet obstruction: Fluid in lesser sac.
 metabilc alkalosis. Malignancy :
Pain 2hour relieved by food Gastric outlet obstruction
epigastric pain metabilc alkalosis
Hunger pain causes obesity Pain <1/2 causes epigastric pain
Rx: UGIE+CAUTERIZATION Rx: Fluid resusciation
A chronic ulcer extends to below the
Gastric and duodenal ulcers coexist in muscularis mucosae and the histology
10% of patients and more than one shows four layers: surface debris, an
peptic ulcer is found in 10-15% of infiltrate of neutrophils, granulation tissue
patients. and collagen.

26. 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.

27. 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.

29. Gastric lymphoma
• 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').

30. Methods for the diagnosis of Helicobacter Pylori infection
Invasive Non Invasive
1. Endoscopy based Biopsy 1. Urea Breath tests:
Urease test  Here patient drinks a labelled urea
Here specimen from antral biopsy are solution and blows into a tube.
tested for ―urease‖.  If H.Pylori urease is present, the
It is most convenient endoscopy urea is hydrolysed and labelled co2
based test. is detected in breath samples.
 It is thus a simple, safe test and
It is quick and simple however it is cheaper than endoscopy.
neither fully sensitive nor fully specific. 2. Serological :
2. Histology :  Here specific IgG lelvels in serum
Here the biopsy specimen is are assessed.
subjected to histological examination,  Does not differentiate between
It is accurate, but time consuming. active and remote infection.
3. Culture:  Nevertheless it is particularly suited
as an epidemiological tool.
Here the biopsy specimen put in a 3. Stool antigen test:
culture medium.
 New test appears less accurate than
This is accurate and permits urea breath test.
determination of antibiotic  Useful for follow up after treatment.
susceptiblities, but is also time
consuming

31. 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.

32. 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.

33. Pathology of Gastritis and Peptic Ulceration
Hematoxylin and eosin; magnification, ×100.
H&E ×25.

35. Indications of treatment :
H. Pylori related duodenal and gastric ulceration Low garde B cell
MALT lymphoma

36. TREATMENT FOR GASTRIC ADENOCARCINOMA
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.

37. 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.

38. Assessing success of treatment/eradication of H.pylori
Non invasive test are Invasive tests are not
preferred preferred
 UREA BREATH TEST:  BIOPSY BASED TESTS
Test of chioce for documenting (Biopsy Urease
eradication. Test,Histology/culture)
 STOOL ANTIGEN TEST: are invasive tests based on
If UBT is not available a stool Endoscopic biosy.
antigen test should be
considered for documenting
eradication.
 SEROLOGICAL TESTING: Is These may be used to document
not useful for purpose of eradication but are not
documentation of eradication preferred for this purpose.
as antibody titres fall slowly
and often do not become
undetectable.