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Peptic ulcer disease

SYAHARA

Peptic ulcer disease


Pathophysiology

The normal stomach maintains a balance


between :
protective factors such as :
-mucus and bicarbonate secretion
aggressive factors such as :
-acid secretion and pepsin.
Gastric ulcers develop when aggressive
factors overcome protective mechanisms.

The two major etiological factors for PUD are :


1. Helicobacter pylori infection
2. Nonsteroidal anti-inflammatory drug (NSAID) consumption.
3. Helicobacter pylori infection
Currently, 70% of all gastric ulcers occurring in the United States can be
attributed to H pylori infection.
The bacterium's spiral shape and flagella facilitate its penetration into the
mucous layer and its attachment to the epithelial layer it releases :
-phospholipase and proteases, which cause further mucosal damage.
-A cytotoxin-associated gene (cag A) has been isolated in
approximately 65% of the bacteria. The products of this gene are
associated with more :
- severe gastritis,
- gastric ulcer
- gastric cancer, and lymphoma

2. Nonsteroidal anti-inflammatory drug (NSAID) consumption.


NSAID-induced ulcers account for approximately 26% of gastric ulcers, and
they are believed to be secondary to a decrease in prostaglandin production
resulting from the inhibition of cyclooxygenase.
The topical effects of NSAIDs are :
-superficial gastric erosions and petechial lesions.
However, the risk of gastroduodenal ulcer is not diminished with parental or
rectal use of NSAIDs indicating injury occurring from the systemic effect of
NSAIDs on the gastrointestinal mucosa.
Selective COX-2 (cyclooxygenase) inhibitors, like celecoxib (Celebrex),
In the Celecoxib Long-term Arthritis Safety Study (CLASS), they found a
significantly lower incidence of symptomatic ulcers in patients taking
celecoxib for the initial 6 months as compared to patients taking ibuprofen or
diclofenac.
Currently, the only US Food and Drug Administration (FDA)-approved COX-2
inhibitor available is celecoxib, as rofecoxib and valdecoxib were withdrawn
from the market by the FDA because of increased cardiovascular risk.

Cigarette smoking can affect gastric mucosal defense adversely.


People who smoke tend to develop more frequent and recurrent ulcers and
their ulcers are more resistant to therapy.
No evidence indicates that dietary habits or alcohol consumption predisposes
individuals to gastric ulcer.

HISTORY

In 1875, German scientists found spiral-shaped bacteria in the lining of


the human stomach. The bacteria could not be grown in culture and
the results were eventually forgotten.[2]
In 1892, the Italian researcher Giulio Bizzozero described spiralshaped bacteria living in the acidic environment of the stomach of
dogs.
The bacterium was rediscovered in 1979 by Australian
pathologist Robin Warren, who did further research on it with
Barry Marshall beginning in 1981; they isolated the organisms
from mucosal specimens from human stomachs and were the
first to successfully culture them.[4] In their original paper,[5]
Warren and Marshall contended that most stomach ulcers and
gastritis were caused by infection by this bacterium and not
by stress or spicy food as had been assumed before.[6]
In 2005, Warren and Marshall were awarded the
Nobel Prize in Medicine for their work on H. pylori.[10]

Helicobacter pylori is a
Gram-negative bacterium that infects the lining of the stomach and duodenum.
Many cases of peptic ulcers, gastritis, and duodenitis are caused by H. pylori
infection.
However, many who are infected do not show any symptoms of disease.
Helicobacter spp. are the only known microorganisms that can thrive in the
highly acidic environment of the stomach.
Its helical shape (from which its name is derived) is thought to have evolved to
penetrate and colonize the mucus lining.[1]

Structure
H. pylori is a spiral-shaped gram-negative bacterium, about
3 micrometres long with a diameter of about 0.5 micrometre. It has 46
flagella. It is microaerophilic, i.e. it requires oxygen but at lower levels
than those contained in the atmosphere. It contains a hydrogenase which
can be used to obtain energy by oxidizing molecular hydrogen (H2) that is

With its flagella, the bacterium moves through the stomach lumen and drills
into the mucus gel layer of the stomach.
It then finds ways to live in various areas of the stomach.
- inside the mucus gel layer
- above epithelial cells
- and inside vacuoles in epithelial cells.
It produces large amounts of urease enzymes which are localized inside and
outside of the bacterium.
Urease metabolizes urea (which is normally secreted into the stomach) to
ammonia and carbon dioxide which neutralizes stomach acid.
The survival of H. pylori in the acidic stomach is dependant on urease and
eventually dies without it.
The ammonia that is produced is toxic to the epithelial cells, and with other
products of H. pylori, including protease, catalase, and phospholipases,
causes damage to those cells.

Mucus cells.

Schematic of typical animal cell, showing subcellular


components. Organelles: (1) nucleolus (2) nucleus (3)
ribosome (4) vesicle (5) rough endoplasmic reticulum (ER)
(6) Golgi apparatus (7) Cytoskeleton (8) smooth ER (9)
mitochondria (10) vacuole (11) cytoplasm (12) lysosome
(13) centrioles

Diagnosis of infection is usually made by checking


for dyspepetic symptoms and then doing tests which
can suggest H. pylori infection.
One can test noninvasively for H. pylori infection
with a
- blood antibody test
-stool antigen test,
-carbon urea breath test (in which the patient drinks
14
C- or 13C-labelled urea, which the bacterium
metabolizes producing labelled carbon dioxide that
can be detected in the breath).
However, the most reliable method for detecting
H .pylori infection is a biopsy check during
endoscopy with a rapid urease test, histological

Immunohistochemical staining of H. pylori from a gastric biopsy.

Treatment of infection
In peptic ulcer patients where infection is detected, the normal procedure is
eradicating H. pylori to allow the ulcer to heal.
Today the standard triple therapy is ( 7- 14 days ):
Triple therapies are used. Worldwide, accepted treatment regimens are
-BMT,
-LAC,
-OAC.
BMT regimen is based on the administration of bismuth subsalicylate,
metronidazole, and tetracycline. Add an H2-receptor antagonist for an additional 4
wk.
LAC regimen is based on the administration of lansoprazole, amoxicillin, and
clarithromycin.
OAC regimen is based on the administration of omeprazole, amoxicillin, and
clarithromycin.

Gastric cancer association


Gastric cancer and gastric MALT lymphoma
(lymphoma of the
mucosa-associated lymphoid tissue) have been
associated with H. pylori, and the bacterium has
been categorized as a group I carcinogen by the
International Agency for Research on Cancer (IARC).

Photograph of H. pylori

G raham patch