PEPTIC ULCER DISEASE

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1. INTRODUCTION
Dyspepsia means acute or chronic pain or discomfort felt
in the upper abdomen. Dyspepsia is a common medical
complaint and peptic ulcer disease is a common cause of
dyspepsia (McPhee et al, 2008).
2. DEFINITION OF PEPTIC ULCER DISEASE
The word peptic relates to pepsin (or acid); thus, peptic
ulcer disease points to gastric and-or duodenal ulcer or
erosion (Shashidhar et al, 2009). Calam (2005, p. 3896)
suggested a peptic ulcer is a breach in the epithelium that
penetrates the muscularis mucosa layer, which if not
breached and then it is an erosion.
3. AETIOLOGY OF PEPTIC ULCER DISEASE
Eenvironmental and hereditary factors influence
common medical diseases including peptic ulcer
although Helicobacter pylori and non-steroidal anti-
inflammatory drugs’ (NSAID) use are main aetiological
factors for peptic ulcer (liu et al, 2009.
3.1 Helicobacter pylori
It is a helical (spiral) shaped microaerophilic gram-
negative bacillus. It has four to six sheathed flagella. The
organism is slowly growing in vitro and grows on blood
agar and selective blood agar medium (Skirrow’s)
(Malaty, 2007). The organism produces urease and
mucolytic proteases that are important for its survival
and pathogenic effect. The organism’s virulence factors
needed for colonization includes motility, adhesins,
proteases, phospholipases, cytokines, cytotoxins and
urease. Urease most likely protects the organism from the
acidic environment (Sedlack and Viggiano, 2008).
3.2 NSAID (Non-steroidal anti-inflammatory drugs)
NSAID use is a common cause of peptic ulcer disease.
Within 14 days after the start of such treatment, about
5% of patients develop gastric mucosal erosions or
ulcers. If usage continues for 4 weeks or longer, this
proportion increases to 10%. The risk of developing ulcer
with NASID use is higher in older patients, patients with
a previous history of ulcer and in patients who use
corticosteroids (Kuipers and Blaser, 2007).
3.3 Environmental factors (smoking, stress and diet)
Duggan and Duggan (2006) suggested a link between
smoking and peptic ulcer disease. About diet, they
perceived little evidence in the literature correlating
alcohol, caffeine and fibre intake to peptic ulcer disease.
They suggested high sugar intake correlates to duodenal
ulcer, while high salt intake links to increased gastric
ulcer risk. Stress influences duodenal ulcers more than
gastric ulcer (Szabo et al, 2007).
3.4 Genetic considerations
Duggan and Duggan (2007) suggested that 39% to 62%
of susceptibility to peptic ulcer disease is explainable on
hereditary basis. They suggested heredity is determining
to the acquisition of Helicobacter pylori, with no link
between genetic factors responsible for developing peptic
ulcer and those responsible for Helicobacter acquisition.
4. PATHOGENESIS OF PEPTIC ULCER DISEASE
Gastric HCl production is stimulated by gastrin secreted
by G cells in the antrum, acetylcholine released by the
vagus nerve and histamine released by enterochromaffin-
like (ECL) cells, all of which stimulate receptors on acid-
producing parietal cells. Duodenal ulcers are rare in
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people who do not produce gastric acid and gastric acid
production is usually low in people with gastric ulcers
(Keshav, 2004).
Helicobacter pylori infection of the gastric antrum
stimulates gastrin production, causing greater
hyperacidity and duodenal ulceration. While infection of
the gastric corpus, where most parietal cells are present,
reduces stomach acid production and is associated with
gastric ulcer. Strains of H. pylori vary in pathogenicity
and virulence, determined by various bacterial gene
clusters. Peptic ulceration results from an imbalance
between gastro-protective factors and disease
aggravating factors, such as stomach acid and the effects
of smoking, alcohol and NSAIDs (Logan et al, 2002).
5. DIAGNOSIS OF PEPTIC ULCER DISEASE
5.1 History and physical examination
Severity of symptoms relates to the presence of multiple
duodenal ulcers, ulcers distal to the duodenal bulb, a
strong family history, ulcers that are refractory to medical
therapy and ulcers that recur after surgery. Peptic ulcers
in subjects who are H pylori-negative and negative for
NSAIDs may point to Zollinger–Ellison syndrome.
Complications relate to NSAID use or chronic peptic
ulcers, the development of ulcer symptoms or a change
in symptoms pattern precede the onset of complications.
However, complications are the presenting symptom of a
peptic ulcer disease in clinically silent cases. Penetrating
ulcers usually present with a change of the character of
pain from the vague visceral discomfort to a localized
and intense pain radiating to the back; besides, the
expected relief of food or antacids diminishes. Vomiting
is a key feature in cases of pyloric outlet obstruction and
bleeding peptic ulcer may be preceded by nausea and is
in the form of haematemesis or melena (Soll and
Graham, 2008), (table 1).
Table (1) Symptoms of gastric ulcer, duodenal ulcer and
non-ulcer dyspepsia
(Adapted from Soll and Graham, 2008)
5.2 Diagnostic work up
Upper GIT endoscopy is a key to diagnosis of peptic
ulcer disease, complication and for differential diagnosis
from other causes of dyspepsia. In addition, endoscopic
healing is the gold standard in treatment evaluation.
Upper GIT double-contrast radiography may be of equal
diagnostic accuracy. However, radiological studies are
not as sensitive as endoscopy especially for the diagnosis
of small ulcers (less than 0.5 cm). Further, radiological
studies do not allow biopsy needed for differential
diagnosis, ruling out malignancy or access to H pylori
infection diagnosis. The main indication for CT scan is
when considering other associated condition and chest x-
ray is useful to detect free abdominal air in case
perforation is a possibility (Calam, 2005).
Diagnosis of H pylori infection by non-invasive methods
as serological tests depends on identification of the
organism’s specific IgG antibodies. Breath test where the
patient drinks C13 or C14 labeled urea, since H pylori
rapidly metabolizes urea, C13 or C14 is absorbed and is
expired as CO2 and can be used as an indication of
infection. Invasive (endoscopy dependent) methods
include the biopsy urease test, which depends on the
organism’s ability to produce urease. Histological
identification of the organism and finally, culture of the
biopsy specimen is useful for antibiotic susceptibility
testing (Chey et al, 2007), (table 2).
Table 2: Comparative accuracy, availability and costs of
H pylori diagnostic tests
(Adapted from Logan et al, 2002, page 18)
6- COMPLICATIONS OF PEPTIC ULCER DISEASE
Upper gastrointestinal bleeding (haematemesis) occurs in
nearly 15 to 20% of patients with peptic ulcer disease. It
is the commonest indication for surgery. Perforation of a
peptic ulcer, in duodenal ulcer, the risk of perforation is
nearly 60% and is less in antral or lesser curvature ulcers.
Perforation of a peptic ulcer leads to chemical and or
bacterial peritonitis, which is a surgical emergency.
Peptic ulcer disease causes gastric outlet obstruction in
nearly 5 to 8% of cases; which develops as a result of
inflammation, spasm, oedema, or scarring and fibrosis of
the ulcer area. It is suspected with the onset of recurrent
episodes of vomiting of large amounts containing
undigested food. In long standing cases, hypochloraemic,
hypoalkalaemic alkalosis occur with weight loss and
dehydration (Ramakrishnan, 2007).
7- TREATMENT OF PEPTIC ULCER DISEASE
7.1 Anti-secretory drugs
Histamine H2-receptor antagonists (H2RAs) are
competitive reversible inhibitors of histamine binding at
H2-receptors on parietal cells. They are effective and
safe but differ in potency with cimetidine is the least
potent of the H2RAs and has the highest incidence of
side effects and drug–drug interactions. Proton pump
inhibitors (PPIs), act by blocking acid secretion at the
hydrogen–potassium adenosine triphosphatase (H+, K+-
ATPase) pump cited on the luminal border of the gastric
parietal cell. Normally, this pump exchanges hydrogen
for potassium across the parietal cell microvillus
membrane; secreting hydrogen ions into the gastric
lumen, thus, creating the low pH environment
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characteristic of gastric secretions. Proton pump
inhibitors bind to and irreversibly inhibit the adenosine
triphosphatase and are the most effective anti secretory
agents and achieving better pH control. Gastric HCl
affects PPIs and they become inactivated if permitted to
dissolve in acidic gastric juice. The third group is
prostaglandins; misoprostol (Cytotec) is a 15-deoxy-15-
hydroxy-16-methyl analogue of prostaglandin E1. It has
the same properties as other E-type prostaglandins,
displaying moderate inhibition of basal and food-
stimulated acid secretion in humans. Their main side
effects are cramp-like abdominal pain and diarrhea,
which are dose-dependent effects (soll and Graham,
2008).
7.2 Eradication of H pylori infection
The combination of a proton pump inhibitor,
clarithromycin and amoxicillin or metronidazole seems
successful especially if treatment extends for more than
seven days (triple therapy). A sequential treatment
regimen developed because of increased bacterial
resistance, it consists of a proton pump inhibitor and
amoxicillin for five days; followed by five additional
days of a PPI, clarithromycin and tinidazole
(Malfertheiner et al, 2007).
7.3 Recurring or a refractory peptic ulcer
A refractory ulcer is usually more than 0.5 cm, resistant
to PPI treatment for 6-8 weeks or H2RAs treatment or 8-
10 weeks. In these cases a careful search for H pylori is
highly recommended (Yuan et al, 2006). Hermansson et
al (2009, page 25) inferred that since the introduction of
PPI drugs, the incidence of peptic ulcer disease
complication has significantly decreased. On the other
hand, Gisbert et al (2006) inferred that eradication H.
pylori infection is more efficient than anti secretory non-
eradicating therapy in preventing recurrent bleeding from
peptic ulcer (figure 1).
Figure 1:Treatment Algorithm of peptic ulcer disease.
(EGD= Oesphagogastroduodenoscop.( Adapted from
Ramakrishnan, 2007 p. 1009)
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