Peptic Ulcer Disease( PUD):
.
Introduction:
 Discontinuation of the mucous membrane of the GIT.
 Acute or chronic; both penetrate the muscularis mucosae
but in acute ulcer no evidence of fibrosis.
 Erosions do not penetrate the muscularis mucosae.
 Locations: duodenum, stomach, lower oesophagus, or in
the jejunum after Gastrojejunostomy or, rarely, in the
ileum adjacent to a Meckel's diverticulum.

GASTRIC & DUODENAL ULCER :
 The prevalence is decreasing in Western communities as a
result of widespread H. pylori eradication, but high in
developing countries.
 Male/female for DU 5:1-2:1, for GU is 2:1 or less.
Aetiology:
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H Pylori.
NSAIDs.
Smoking.
Genetics.
Aetiology: H pylori
 The most important cause.
 HP prevalence rises with age, 50% > 50 years are infected.
 In developing world HP is much more common, usually
acquired in childhood & up to 90% of the adults are
infected.
 The vast majority of colonised people remain healthy/
asymptomatic& only a minority develop clinical disease.
 90% DU, 70% GU are infected with H. pylori; the
remaining 30% GU are due to NSAIDs.
H pylori: Pathophysio
 H. pylori is Gram-negative, spiral with multiple flagella at
one end which make it motile, allowing it to burrow& live
deep beneath the mucus layer closely adherent to the
epithelial surface.
 It uses an adhesin molecule (BabA) to bind to the Lewis b
antigen on epithelial cells,where the surface pH is close to
neutral & any acidity is buffered by the organism's
production of the enzyme urease.produces ammonia from
urea, raises the pH around the bacterium & between its
two cell membrane layers.
 The bacteria spread by person-to-person contact via
gastric refluxate or vomitus.
 H. pylori exclusively colonises gastric-type epithelium&
found in the duodenum only in association if there are
patches of gastric metaplasia.
H pylori: Pathophysio
 Causes chronic gastritis by provoking a local
inflammatory response in the underlying epithelium,
depends on numerous factors; bacterial factors as
expresion of cagA / vacA genes & host factors.

H pylori: Pathophysio
 Bacterial factots:
 H. pylori strains expressing cagA (cagA+) are more often
associated with disease than cagA- strains.
 Most strains also secrete a large pore-forming protein
called vacA causes large vacuoles to form in cells in vitro.
H pylori: Pathophysio
 Host factors:
 Genetic polymorphisms; for example, greater levels of
expression of the proinflammatory cytokine interleukin-1β
(IL-1β) are associated with greater risk of gastric atrophy
& subsequent carcinoma &polymorphisms in other genes
involved in the host inflammatory response to infection
(e.g. IL-10 / TNF-α) may also be important.
H pylori: Pathophysio
 In most people H. pylori causes antral gastritis associated
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with depletion of somatostatin (from D cells)& gastrin
release from G cells unchecked by somatostatin.
The subsequent hypergastrinaemia stimulates acid
production by parietal cells, but in the majority of cases
this has no clinical consequences.
In a minority of patients (perhaps smokers) this effect is
exaggerated, leading to duodenal ulceration
The role of H. pylori in the pathogenesis of gastric ulcer is
less clear but probably acts by reducing gastric mucosal
resistance to attack from acid/pepsin.
In 1% of infected people, H. pylori causes a pangastritis
leading to gastric atrophy/ hypochlorhydria,allows
bacteria to proliferate within the stomach; these may
produce mutagenic nitrites from dietary nitrates,
predisposing to the development of gastric cancer
Factors which influence the virulence of H. pylori.
HP Diagnosis:
 Urea Breath tests are best because of their accuracy,
simplicity & non-invasiveness.
HP Diagnosis: Others
Test
Advantages
Disadvantages
Rapid office kits available
Lacks sensitivity and specificity
Good for population studies
Cannot differentiate current from past infection
High sensitivity and specificity
14C
uses radioactivity
13C
requires expensive mass spectrometer
NON-INVASIVE
Serology
Urea breath tests
Faecal antigen test
Cheap, accurate
Acceptability
Sensitivity and specificity
False negatives occur
INVASIVE (ANTRAL BIOPSY)
Histology
Takes several days to process
Rapid urease tests, e.g. CLO, Pyloritek
Cheap, quick
Specificity
Lack sensitivity
Microbiological culture
'Gold standard'
Slow / laborious
Defines antibiotic sensitivity
Lacks sensitivity
Smoking:
 Smoking confers an increased risk of gastric ulcer & to a
lesser extent, duodenal ulcer.
 Once the ulcer has formed, it is more likely to cause
complications& less likely to heal if the patient continues
to smoke.
 NSAIDs
Acid-pepsin vs mucosal resistance:
 Ulcer forms when there is imbalance between aggressive
factors, i.e. acid /pepsin & defensive factors, i.e. gastric
/duodenal mucosa, bicarbonte, mucosal blood flow* PGs.
 Ulcers occur only in the presence of acid /pepsin; never
found in achlorhydric as pernicious anaemia& severe
intractable PU nearly always occurs in ZES, characterised
by very high acid secretion.
 Most DU have markedly exaggerated acid secretion in
response to stimulation by gastrin& H. pylori leads to
hypergastrinaemia.
 In GU the effects of H. pylori are more
complex&impaired mucosal defence resulting from a
combination of HP, NSAIDs&smoking have a more
important role.
Gastroduodenal mucosal protection; PG stimulate HCO3
/mucus secretion& increase mucosal blood flow.
Clinical features:
 Chronic with spontaneous relapse /remission lasting for
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decades, if not for life.
DU/GU share common symptoms.
Recurrent abd pain with 3 notable characteristics:
epigastric , episodic & relationship to food .
Occasional vomiting occurs in 40%; persistent daily
vomiting suggests GOO.
In 1/3 history is less characteristic, esp in elderly on
NSAIDs, pain may be absent or slight epigastric unease.
Occasionally, only anorexia / nausea, or a sense of undue
repletion after meals.
In some completely 'silent', presenting for the first time
with anaemia, abrupt haematemesis or as acute
perforation; recurrent acute bleeding.
The diagnostic value of individual symptoms is poor.
Diagnosis:
 Endoscopy is the preferred investigation.
 Gastric ulcers may occasionally be malignant& therefore
must always be biopsied & followed up to ensure healing
Management:
 Aims: relieve symptoms, induce healing ,prevent recurrence.
 H. pylori eradication is the cornerstone of therapy, as this
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will successfully prevent relapse& eliminate the need for
long-term therapy in the majority.
H. pylori eradication All patients with proven acute or
chronic DU &GU who are H. pylori-positive should be
offered eradication as primary therapy.
Treatment is PPI simultaneously with two antibiotics (from
amoxicillin, clarithromycin , metronidazole) for 7 days.
Success is > 90%, although compliance, side-effects&
metronidazole resistance influence the success of therapy.
Second-line therapy should be offered to those patients who
remain infected after initial therapy,choice lies between a
third attempt with quadruple therapy (bismuth, PPI+ 2
antibiotics) or long-term maintenance therapy with PPI.
Management:
 H. pylori / NSAIDs are independent risk factors for ulcer
 High risk patients requiring long-term NSAIDs should
first undergo eradication therapy to reduce ulcer risk.
 This may not be necessary in young, fit patients with no
history of ulcer disease or dyspepsia but a 'test & treat'
strategy for older patients with major comorbidity or a
previous ulcer history is recommended.
 Subsequent co-prescription of PPI+ NSAID is advised but
is not always necessary for patients being given low-dose
aspirin in whom the risk of ulcer complications is lower
COMMON SIDE-EFFECTS OF HP ERADICATION:
 Diarrhoea
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– 30-50%; usually mild but Clostridium difficileassociated colitis can occur.
Flushing & vomiting when taken with alcohol
(metronizadole)
Nausea, vomiting
Abdominal cramp
Headache
Rash
Other indications OF HP ERADICATION:
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Definite
Peptic ulcer
MALToma
H. pylori-positive dyspepsia
Not indicated
Asymptomatic
Gastro-oesophageal reflux disease
Uncertain
Family history of gastric cancer
Non-ulcer dyspepsia
Low risk Long-term NSAID users
General measures:
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Cigarette smoking, aspirin/ NSAIDs should be avoided.
Alcohol in moderation is not harmful.
No special dietary advice is required.
Short-term management: many different drugs are
available for of acid peptic symptoms.
 Maintenance treatment: Continuous maintenance
treatment should not be necessary after successful H.
pylori eradication.
 For the minority who do require it, the lowest effective
dose should be used.
Group
Examples
Mechanism
Comments
antacid
Aluminium
hydroxide,
magnesium
trisilicate,
alginic acid
Antacids; alginates form protective mucosal
'raft'
Aluminium salts block digoxin absorption and are
constipating while magnesium salts can cause
diarrhoea; some have high sodium content and
can exacerbate cardiac failure
H2-Bs
Ranitidine,
cimetidine,
famotidine,
nizatidine
Competitive inhibitors of H2-receptors on
parietal and ECL cells
Less potent than PPIs; good safety profile- some
available without prescription; cimetidine may
interfere with warfarin and phenytoin metabolism
via cytochrome P450
PPI
Omeprazole,
esomeprazole,
lansoprazole,
pantoprazole,
rabeprazole
Irreversible inhibitors of H+/K+ ATPase on
parietal cell surface
Potent acid suppression and rapid ulcer healing; used in
H. pylori therapy; superior to H2 antagonists for
healing ulcers and oesophagitis
Chelat
Tripotassium
dicitratobism
uthate
Ammoniacal suspension of complex bismuth
salt; anti-H. pylori activity and
enhances mucosal protection
May darken tongue and stools
C,Salts
Sucralfate
Aluminium salt of sucrose octasulphate;
little effect on acid -may protect ulcer
base from peptic activity and enhance
epithelial cell turnover
Caution in renal impairment; reports of bezoar
formation
PGs
Misoprostol
Enhance mucosal blood flow, stimulate
mucus and bicarbonate secretion;
stimulate epithelial proliferation
Diarrhoea; abortifacient-contraindicated in women of
child-bearing age
PGE2
_
+
Histamine
+
ACh
M3
Ranitidine
Gastrin
_
Proglumide
_
Misoprostol
PGE
receptor
Ca++
Adenyl
cyclase
ATP
+
+
H2
+
cAMP
+
Gastrin
receptor
Ca++
+
Protein Kinase
(Activated)
K+ + H+
K
_
Omeprazole
Proton pump
Gastric acid
Parietal cell
Lumen of stomach
_
Antacid
Surgery:
 The cure of most peptic ulcers by H. pylori eradication &
availability of safe, potent acid-suppressing drugs have
made elective surgery for PUD a rare event
Complications:
 Perforation
 Ggastric outlet obstruction
 Bleeding
PEPTIC ULCER DISEASE IN OLD AGE:
 Gastroduodenal ulcers: have a greater incidence,
admission rate & mortality.
 Causes: high prevalence of H. pylori & NSAID use&
impaired defence mechanisms.
 Atypical presentations: pain &dyspepsia are frequently
absent or atypical so older people develop complications
such as bleeding or perforation more frequently.
 Bleeding: older patients require more intensive
management (including central venous pressure
measurement) than younger patients because they tolerate
hypovolaemic shock poorly.