Peptic ulcer disease(PUD) is one of the most common gastroenterological diseases warranting GP consultation. This presentation takes a deep look at H. Pylori; The structure of this bacterium and it's patho-physiology in Peptic ulcer disease(causes about 80-85%).

1. H. Pylori “for and against”
in etiology of peptic
ulcer.
BY GBAJIE NNAMDI PETER.

2. H. Pylori and Peptic ulcer disease
 Peptic ulcer disease refers to painful sores or ulcers in the lining of the stomach or first
part of the small intestine, called the duodenum. These sores/ulcers produce many
constitutional symptoms that make the patient seek medical help. Such symptoms as;
• A gnawing or burning pain in the middle or upper stomach between meals or at night
• Bloating
• Heartburn
• Nausea or vomiting
 In severe cases, symptoms can include:
• Dark or black stool (due to bleeding)
• Vomiting blood (that can look like "coffee-grounds")
• Weight loss
• Severe pain in the mid to upper abdomen

3. H. Pylori as major cause of PUD
 It is believed that H. pylori causes about 90% of duodenal ulcers and about
80-85% of gastric ulcers. With this, it’s clear that majority of ulcers are caused
by this bacterium and the study of it’s pathogenesis/pathophysiology and
method of elimination would bring an end to disease progression and relief
to PUD patients. Other minor causes of PUD include;
 NSAIDs
 Smoking and stress
 Heredity
 As complication of other diseases.
 Since scientists and Gastroenterologists world wide are in agreement
about H. pylori being the major cause(ave 85-90%) of PUD, there is no much
argument abt this FACT so, let’s proceed to know about this bacterium and
it’s pathogenesis in PUD.

4. H. Pylori- Pathogenesis in PUD.
 Helicobacter pylori is a Gram-negative, helix-shaped bacterium that is about 3 micrometers
long with a diameter of 0.5 micrometers. H. pylori is a microaerophilic bacterium which
means that it requires oxygen to function. However, H. pylori requires much lower
concentrations of oxygen than those found in our atmosphere. This bacterium contains a
hydrogenase which it can use to obtain energy by oxidizing molecular hydrogen (in the form
of H2) produced by intestinal bacteria. H. pylori also produces oxidase, catalase, and
urease.

5. H. Pylori contd
 It has an outer-membrane consisting of phospholipids and
lipopolysaccharide which are characteristic of typical Gram-negative
bacteria. H. pylori bacteria are known to inhabit
various areas of the stomach and duodenum. Infections
caused by this bacteria lead to chronic inflammation in the
stomach lining (Gastritis). H. pylori infections are also
strongly associated to the development of gastric ulcers and
even stomach cancer. Although H. pylori is known to cause
several problems, over 80% of individuals infected with this
bacterium show no symptoms. Over half of all people in the
world are thought to harbor this bacterium in their upper
gastrointestinal tract.

6. Pathogenesis
 There is no single pathway of transmission for Helicobacter pylori that has been
clearly identified. Scientists have had difficulty locating the bacterium anywhere
outside of gastric tissue. Because of this, it has been difficult for scientists to
locate the portal by which the bacterium is spread. However, scientists do believe
the bacterium is passed from person to person and most transmissions occur
during early life. It has been suggested that transmission may occur in faecal-oral
and oral-oral pathways. Other pathways have not been ruled out. However the
bacterium enters the body it eventually makes its way to the gastrointestinal
tract. H. pylori makes its way into the stomach to begin colonization. In order to
colonize the stomach H. pylori must survive the acidic pH of its environment. It
burrows into the mucous lining that coats the stomach. An H. pylori bacterium has
flagella and uses them to move through the stomach lumen and drill into the
mucous lining of the stomach.

7. Pathogenesis
 H. pylori produces adhesins that bind to membrane-associated lipids and
carbohydrates which helps it to adhere to the epithelial cells. The bacterium
also produces great quantities of urease, and enzyme located inside and
outside of the cell. This enzyme is capable of breaking down urea that is
secreted into the stomach. It breaks down the urea into carbon dioxide and
ammonia. The ammonia is converted into an ammonium ion by accepting a
hydrogen ion from self-ionized water. The left-over hydroxyl ions then react
with the carbon dioxide to produce bicarbonate which neutralizes gastric acid.
Therefore, H. pylori is dependent upon urease for its survival in the acidic
environment found in the stomach. Without the urease enzyme the bacterium
would almost inevitably die. The ammonia that is a byproduct of the urease
reaction is toxic to epithelial cells of the stomach. H. pylori also produces
protease (an enzyme that breaks down proteins), vacuolating cytotoxin A
(VacA), and phospholipases (enzymes that hydrolyze phospholipids into fatty
acids and other lipophilic substances). All of these products are damaging to
the epithelial cells of the stomach.

8. Pathogenesis
 When H. pylori colonizes the stomach it often results in chronic gastritis, an
inflammation of the stomach lining. Stomach and duodenal ulcers occur
when the inflammation allows the acid and pepsin in the stomach lumen to
overpower the mechanisms that protect the stomach and duodenal mucosa
from these substances. The location of the chronic gastritis (which occurs at
the site of H. pylori colonization) dictates the type of ulcer that subsequently
develops. The amount of acid within the stomach lumen has an effect on the
colonization patterns of the bacteriumH. pylori. It will therefore, in the end,
establish the location at which the gastric or duodenal ulcer will form. For
example, in people that produce large amounts of acid, H. pylori will
colonize the pyloric antrum of the stomach to avoid the parietal cells in the
corpus of the stomach that secrete acid.

9.  The inflammatory response to the bacteria induces G cells in the antrum
to secrete the hormone gastrin. Gastrin travels through the bloodstream to
the corpus of the stomach.[8] Gastrin excites the parietal cells in the
corpus to release even more acid into the stomach lumen. Persistently
increased gastrin levels eventually cause the number of parietal cells to
also increase, further increasing the amount of acid secreted.[9] The
increased amount of acid damages the duodenum and may consequently
result in the formation of duodenal ulcers. Gastric ulcers on the other
hand are often linked with reduced or normal levels of acid production.
This suggests that the mechanisms that protect the gastric mucosa are
faulty in that individual.[9] H. pylori capitalizes on this defect and begins to
colonize the corpus of the stomach where the parietal cells are located.
The chronic inflammation caused by the colonization of this bacterium
causes further reduction in the stomach’s acid production, causing
atrophy of the stomach lining. The deterioration of the stomach’s lining
may lead to future gastric ulceration and even an increased risk for
stomach cancer.

10. Diagnosis and Identification of H. pylori
in PUD.
 Once a patient presents with symptoms of Peptic ulcer
disease(Epigastric pain relating to food in take or hunger,
heartburn, nausea or vomiting, stomach bloating,
meteorism, tarry stool, abdominal discomfort after in take
of spicy foods etc) , doctor normally prescribe H. pylori
test as one of the major and most important tests in
management and follow up. This is simple, elimination of
the causative agent plays a great role in complete
treatment of any condition. H. pylori being a major cause
of peptic ulcer disease(85-90%), needs to be checked to
rule out H. pylori +ve PUD or rule in.

11. Invasive and non-invasive method of
H. pylori testing.
 NON-INVASIVE TESTS
 Blood antibody test
 Urea breath test
 Stool antigen test
 INVASIVE TESTS
 Endoscopic Biopsy providing samples
for;
 1) histology
 2)cytology
 3)Rapid urease test
 4) Bacterial culture

12. Non-Invasive method of H. pylori test
 Blood antibody test/Serological test: This is done using
the patient’s blood to test for H. pylori antibodies.
Laboratory and office-based serologic assays for antibodies
to H. pylori have sensitivity and specificity of > 85% and are
considered the noninvasive tests of choice for initial
documentation of H. pylori infection. However, because
qualitative assays remain positive for up to 3 yr after
successful treatment and because quantitative antibody
levels do not decline significantly for 6 to 12 months after
treatment, serologic assays are not usually used to assess
cure

13. H. Pylori serology test kit

14. InstaTest for H. pylori serological test

15. NONIVASIVE TEST contd
 Urea Breath test:
 Urea breath tests use an oral dose of 13C- or 14C-labeled urea. In an
infected patient, the organism metabolizes the urea and liberates labeled
CO2, which is exhaled and can be quantified in breath samples taken 20
to 30 min after ingestion of the urea. Sensitivity and specificity
are > 90%. Urea breath tests are well suited for confirming eradication of
the organism after therapy. False-negative results are possible with
recent antibiotic use or concomitant proton pump inhibitor therapy;
therefore, follow-up testing should be delayed ≥ 4 wk after antibiotic
therapy and 1 wk after proton pump inhibitor therapy. H2 blockers do not
affect the test.


16. Urea breath test

18. NON-INVASIVE TESTS contd
 Stool antigen test: Stool antigen assays
seem to have a sensitivity and specificity near
that of urea breath tests, particularly for initial
diagnosis; an office-based stool test is under
development.

19. INVASIVE TEST
 In other to perform any of the previously listed invasive
methods, Endoscopy is used to obtain mucosal biopsy
samples for a rapid urease test (RUT) or histologic staining.
Bacterial culture is of limited use because of the fastidious
nature of the organism. Endoscopy is not recommended
solely for diagnosis of H. pylori; noninvasive tests are
preferred unless endoscopy is indicated for other reasons.

20. INVASIVE TEST
 The RUT, in which presence of bacterial urease in the biopsy
sample causes a color change on a special medium, is the
diagnostic method of choice on tissue samples. Histologic
staining of biopsy samples should be done for patients with
negative RUT results but suspicious clinical findings, recent
antibiotic use, or treatment with proton pump inhibitors. RUT
and histologic staining each have a sensitivity and specificity
of > 90%.


21. Endoscopic biopsy

22. Rapid urease test

23. Histology of biopsy showing H. pylori

24. Bacteriological culture of H. pylori

25. The case for or against H. pylori in PUD
 It’s been proved through various studies that H. pylori is the key
etiological factor in PUD based on prevalence and incidence. It is
worth elaborating also that, some other etiological or better still, risk
factors like heredity, long term use of NSAIDs, smoking, stress and
association of other diseases play little roles as etiological factors. In
some cases, there might be multiple factors like; combination of H.
pylori and NSAIDs or Heredity and NSAIDs.
 It is known that NSAIDs when used for a long period( aspirin,
ibuprofen (Advil, Motrin IB, others), naproxen (Aleve, Anaprox, others),
ketoprofen and others) damage gastric mucosal barrier and are
important etiologic factor in abt 30% cases.

26.  Heredity: Peptic ulcer tends to run in families and 2 specific factors
identified are;
 1) Larger parietal cell mass with increased gastric acid output in patients
with duodenal ulcer perhaps represents an inborn characteristic of the
individual.
 2) Blood group and Blood group antigen; Those with blood group O and
those unable to secrete their blood group antigen into the saliva and
gastric juice are more predisposed to peptic ulcer.
 The hereditary component analyzed above contribute about 5-10% as an
etiological factor and can’t be compared to the whooping 80-90% case in
H. pylori incidence.

27. Summary
 Due to the overwhelming believe that H. pylori is the
major cause of peptic ulcer(though other factors like
listed earlier are also acknowledged but, their roles re so
little), the H. pylori eradication therapy has been included
in guidelines for treatment of patients with PUD and
chronic gastritis or gastroduodenitis.
 The H. pylori therapy is divided into two: triple and
quadruple therapy.
 Triple therapy is recommended. Oral omeprazole 20 mg bid
or lansoprazole30 mg bid, plus clarithromycin 500 mg bid,
plus amoxicillin1 g bid (or, for penicillin-allergic patients,
metronidazole 500 mg bid) for 14 days, cures infection

28. Summary
 Quadruple therapy with a proton pump inhibitor bid, tetracycline 500 mg and
bismuth subsalicylate or subcitrate 525 mg qid, and metronidazole 500 mg tid
is also effective but more cumbersome.
 Infected patients with duodenal or gastric ulcer require continuation of the
acid suppression for at least 4 wk.
 Treatment is repeated if H. pylori is not eradicated. If two courses are
unsuccessful, some authorities recommend endoscopy to obtain cultures for
sensitivity testing.
 Lastly, it is worth pointing out that, although H. pylori dominates as the
etiological factor in PUD, the roles of stress, heredity, long-term use of
NSAIDs, smoking and association of other diseases should not be neglected.
 THANK YOU