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Peptic Ulcer Disease (PUD) – Dr. Taha

• 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.

• Etiology: H Pylori, NSAIDs, Smoking, Genetics

Etiology: 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: Pathophysiology

• 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.

• 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.

• Bacterial factors:

� H. pylori strains expressing cagA (cagA+) are more often associated with disease than cagA- strains.

� Most strains secrete a large pore-forming protein called vacA causes large vacuoles to form in cells in vitro.

• 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.

• In most people H. pylori causes antral gastritis associated 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

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HP: Diagnosis

Urea Breath tests are best because of their accuracy, simplicity & non-invasiveness.

Test Advantages Disadvantages

NON-INVASIVE

Serology Rapid office kits available Lacks sensitivity and specificity

Good for population studies Cannot differentiate current from past

infection

Urea breath tests High sensitivity and specificity 14

C uses radioactivity

13

C requires expensive mass

spectrometer

Faecal antigen test Cheap, accurate Acceptability

INVASIVE (ANTRAL BIOPSY)

Histology Sensitivity and specificity False negatives occur

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.

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Gastroduodenal mucosal protection; PG stimulate HCO3 /mucus secretion& increase mucosal blood flow.

Clinical Features

• Chronic with spontaneous relapse /remission lasting for 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 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.

• 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

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COMMON SIDE-EFFECTS OF HP ERADICATION

• Diarrhoea

o 30-50%; usually mild but Clostridium

difficile-associated colitis can occur.

• Flushing & vomiting when taken with alcohol

(metronizadole)

• Nausea, vomiting

• Abdominal cramp

• Headache

• Rash

Other indications OF HP ERADICATION

• Definite

o Peptic ulcer

o MALToma

o H. pylori-positive dyspepsia

• Not indicated

o Asymptomatic

o Gastro-oesophageal reflux disease

• Uncertain

o Family history of gastric cancer

o Non-ulcer dyspepsia

o Low risk Long-term NSAID users

General Measures

• 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

dicitratobismuthate

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

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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.