Peptic Ulcer Disease( PUD):

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Peptic Ulcer Disease( PUD)

• .

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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.

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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 51-21, for GU is 21 or
  less.

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Aetiology

• H Pylori.
• NSAIDs.
• Smoking.
• Genetics.

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Aetiology H pylori

• The most important cause.
• HP prevalence rises with age, 50 gt 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.

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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.

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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.

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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.

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H pylori Pathophysio

• Host factors
• Genetic polymorphisms for example, greater
  levels of expression of the proinflammatory
  cytokine interleukin-1ß (IL-1ß) 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-a) may also be important.

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H pylori Pathophysio

• 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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Factors which influence the virulence of H.
pylori.
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HP Diagnosis

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

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HP Diagnosis Others
Test Advantages Disadvantages
NON-INVASIVE NON-INVASIVE 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 14C uses radioactivity
    13C requires expensive mass spectrometer
Faecal antigen test Cheap, accurate Acceptability
INVASIVE (ANTRAL BIOPSY) INVASIVE (ANTRAL BIOPSY) INVASIVE (ANTRAL BIOPSY)
Histology Sensitivity and specificity False negatives occur
    Takes several days to process
Rapid urease tests, e.g. CLO, Pyloritek Cheap, quickSpecificity Lack sensitivity
Microbiological culture 'Gold standard' Slow / laborious
  Defines antibiotic sensitivity Lacks sensitivity
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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

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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
  compleximpaired mucosal defence resulting from a
  combination of HP, NSAIDssmoking have a more
  important role.

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

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Diagnosis

• Endoscopy is the preferred investigation.
• Gastric ulcers may occasionally be malignant
  therefore must always be biopsied followed up
  to ensure healing

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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 gt 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.

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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

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COMMON SIDE-EFFECTS OF HP ERADICATION

• Diarrhoea
• 30-50 usually mild but Clostridium
  difficile-associated colitis can occur.
• Flushing vomiting when taken with alcohol
  (metronizadole)
• Nausea, vomiting
• Abdominal cramp
• Headache
• Rash

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Other indications OF HP ERADICATION

• 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

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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.

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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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PGE2
Gastrin
Histamine
Proglumide
ACh
H2
M3
Adenyl cyclase
Gastrin receptor
PGE receptor
ATP
cAMP
Ca
Ca
Protein Kinase (Activated)
K
H
K
Parietal cell
Proton pump
Lumen of stomach
Gastric acid
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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

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Complications

• Perforation
• Ggastric outlet obstruction
• Bleeding

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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.