Title: Peptic Ulcer Disease( PUD):
1Peptic Ulcer Disease( PUD)
2Introduction
- 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. -
3GASTRIC 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.
4Aetiology
- H Pylori.
- NSAIDs.
- Smoking.
- Genetics.
5Aetiology 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.
6H 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.
7H 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. -
8H 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.
9H 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.
10H 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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13Factors which influence the virulence of H.
pylori.
14HP Diagnosis
- Urea Breath tests are best because of their
accuracy, simplicity non-invasiveness.
15HP 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
16Smoking
- 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
17Acid-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.
18Gastroduodenal mucosal protection PG stimulate
HCO3 /mucus secretion increase mucosal blood
flow.
19Clinical 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.
20Diagnosis
- Endoscopy is the preferred investigation.
- Gastric ulcers may occasionally be malignant
therefore must always be biopsied followed up
to ensure healing
21Management
- 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.
22Management
- 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
23COMMON 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
24Other 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
25General 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.
26Group 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
27PGE2
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
28Surgery
- 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
29Complications
- Perforation
- Ggastric outlet obstruction
- Bleeding
30PEPTIC 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.