H. Pylori “for and against”

in etiology of peptic

ulcer.

BY GBAJIE NNAMDI PETER.

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

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.

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.

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.

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.

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.

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.

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.

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.

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

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

H. Pylori serology test kit

InstaTest for H. pylori serological test

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.

Urea breath test

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.

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.

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%.

Endoscopic biopsy

Rapid urease test

Histology of biopsy showing H. pylori

Bacteriological culture of H. pylori

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.

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.

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

in > 95% of cases. This regimen has excellent tolerability.

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.

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