Presentation on peptic ulcer disease in detail

1. AETIOPATHOPHYSIOLOGY
OF PEPTIC ULCER DIESEASE
PRESENTER- DR.PRINCE LATHIYA(2ND YEAR PGT)
MODERATOR- DR.S.B.CHOUDHURY(ASST PROF )

2. Introduction
•Peptic ulcers are defined as erosions in the gastric or
duodenal mucosa that extend through the muscularis
mucosa.
•PUD is most common GI disorder.
•Caused by imbalance b/w defensive and damaging
factors.
•Common site – first part of duodenum and lesser
curvature of stomach.
•Prevalance of PUD has decresed over past 30 yrs due
to use of eradication therapy.
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4. Etiology
1. H. pylori infection
2. NSAIDs
3. Stress
4. Smoking
5. Diet
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5. Gastric physiology
•Gastro duodenal Mucosal Defense:
The mucosal defense system can be divided as a three level barrier
1. Preepithelial
2. Epithelial
3. Subepithelial
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7. Pathophysiology
•Most of the gastric and peptic ulcers are caused by H.pylori infection and NSAIDs use.
•H.pylori predisposes to ulceration, both by acid hypersecretion and by compromise of mucosal
defence mechanism
•NSAID use causes ulcers predominantly by compromise of mucosal defence
•A variety of other diseases are known to cause peptic ulcer
1. ZES
2. Antral G cell hyperplasia
3. Systemic mastocytosis
4. Trauma
5. Burns and major physiologic stress
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9. Pathogenesis
•Imbalance b/w damaging factors and defensive factors
•Defensive factors- 1. mucosal bicarbonate secretion
2.mucus production
3.blood flow
4.growth factors
5.cell renewal
6.endogenous prostaglandins
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10. •Damaging factors -1.HCL secretion
2.pepsins
3.alcohol
4.smoking
5.duodenal reflux of bile
6.ischemia
7.NSAIDs
8.hypoxia
9.H.pylori infection
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11. Pathophysiology
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12. H.PYLORI INFECTION
•First elucidated by Marshall and warren in Australia 1984 .
•80-95% of duodenal ulcers and approx. 75% of gastric ulcers are
due to h.pylori infection
•Spiral or helical gram negative rod with four to six flagella- its
shape and flagella helps for movements through mucus layer
•Resides in gastric type epithelium within or beneath the mucosal
layer
•It produces urease , that splits urea into ammonia and
bicarbonate , creates alkaline microenvironment
•Can also be found in proximal oesophagus, in gastric metaplasia
in the duodenum, within a meckel’s diverticulum and ectopic
gastric mucosa
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13. •Mutant strain that lack flagella are unable to navigate through the unstirred mucus layer to get
to the apical membrane of SEC for the attachment and are non pathogenic.
•H.pylori can induce gastroduodenal mucosal injury include the
1. Production of toxins(vacA and cagA),
2. Local elaboration of cytokines,
3. Recruitment of inflammatory cells and release of inflammatory mediators,
4. Recruitment and activation of local immune factors
5. Increased apoptosis.
•Patients with H.pylori infection and antral gastritis are three and half times more likely to
develop PUD than patients without infection.
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14. Cytotoxins
•VacA :- it increases cell permeability,
efflux of micronutrients from epithelium,
induction of apoptosis,
suppression of local immune cell activity
•CagA : it interacts with numerous cell signaling pathways
involved in cell replication and causes apopotsis
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17. Mechanisms resposinble for H.pylori
induced GI injury
1. Production of toxic products that cause local tissue injury
breakdown products from urease activity, cytotoxins, mucinase that degrades mucus and
glycoprotein, phospholipase that damage epithelial cells and mucus cells and platelet
activating factors cause mucosal injury and thrombosis In the microcirculation
2. Induction of a local mucosal immune response
it can cause local inflammatory reaction in the gastric mucosa attracting neutrophils and
monocytes
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18. 3. Increased gastrin levels with a resultant increase in acid secretions
Basal and stimulated gastrin levels increase due to reduction in antral D cells bcz of infection
with H.pylori .
Decrease in serum levels of somatostatin as a result of H.pylori infection which increase
gastrin and acid secretion
4. Gastric metaplasia occurring in the duodenum
Metaplastic replacement of areas of a duodenal mucosa with gastric epithelium due to
protactive response to decrease duodenal PH, allows H.pylori to colonize in the duodenum
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19. • 95% pts infected with H.pylori have histologic evidence of antral gastritis
•H.pylori infection usually occurs in childhood, spontaneous remission is rare
•Inverse relationship b/w infection and socioeconomic status
•Higher rate of infection in developing countries may be due to sanitary condition, familial
clustering and crowding.
•H.pylori infection is almost always present in the setting of active chronic gastritis
•Most patients with gastric cancer have current or past H.pylori infection
•Strong association b/w mucosa-associated lymphoid tissue(MALT) lymphoma and H.pylori
infection
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20. Multiple factors(smoking,age)
Incresed acid secretion
Gastric metaplasia in
duodenum
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Acquisition of
H.pylori
Chronic H.pylori
infection
Somatostatin/gastrin
dysregulation
H.Pylori colonization in duodenum
Inflammation(Duodenitis)Duodenum bicarbonate secretion
Duodenum ulceration

21. Acid secretion and Peptic ulcer
•Many duodenal ulcer patients as a group have a higher mean BAO compared to normal control,
many duodenal ulcer patients have basal and peak acid output in the normal range . So no
correlation b/w acid secretion and severity of the ulcer disease.
•Duodenal ulcer pts produce more acid than normal control in response to any known acid
secretory stimulus
•DU patients often produce more gastric acid at any given doses of gastrin than control, although
they have normal fasting serum gastrin levels.
•Some pts with DU shows increased rate of gastric emptying
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22. Classification of gastric ulcer
•Type 1-most common, located near incisura
angularis
•Type 2-gastric ulcer associated with active or
quiescent duodenal ulcer
•Type 3-prepyloric ulcer
•Type 4-gastric ulcer near GE junction
•Type 5-NSAIDs induced
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23. •Type 1 gastric ulcer usually have normal or decreased acid secretion
•Type 2 and Type 3 gastric ulcers are associated with normal or increased gastric acid secretion
•Type 4 gastric ulcers have normal or below normal acid secretion
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24. NSAIDs
• 2nd most common cause of PUD
•Increases risk of peptic ulcer disease about 5 fold and upper GI bleeding about 4 fold
•Risk is proportional to the daily dosage of NSAIDs
•The overall risk of significant serious adverse GI events in pts taking NSAIDs is more than 3 times that
of controls and it increase 5 times in pts >60 yrs old.
•Absorbed through stomach and small intestine and function as systemic inhibitors of the
cyclooxygenase enzyme, which is rate limiting step of prostaglandine synthesis
•Prostaglandine promote gastric and duodenal mucosal protection by increasing mucin and
bicarbonate secretion and increasing blood flow to the mucosal epithelium
•Three patterns of mucosal damages are caused by NSAIDS.
They are superficial erosions, haemorrhages and silent ulcers.
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25. Smoking
•Smoking increase risk of gastric ulcer and duodenal ulcer by 2 fold
• Once the ulcer has formed, it is more likely to cause complications and less likely to heal if the
patient continues to smoke
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26. Features Duodenal ulcres Gastric ulcers
1. Incidence
2.Etiology
i. Four times more common than gastric
ulcers ii. Usual age 25 – 50 years
iii. More common in males than
females(4:1)
Most commonly as a result of H.pylori
infection other factors like Hyper secretion
of acid and pepsin, association with
alcoholic cirrhosis, tobacco, chronic
pancreatitis
Less common than
duodenal ulcers
Usually beyond the 6 th
decade More common in
males than females
Gastric colonisation with
H.pylori asymptomatic but
higher chances of
development of duodenal
ulcer. Distruption of mucus
barrier most important factor
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27. Features Duodenal ulcers Gastric ulcers
3. Pathogenesis i. Mucosal digestion from
hyper acidity most
significant factor.
ii. ii. Protective gastric
mucus barrier may be
damage
Association with gastritis, bile
reflux, drugs, alcohol. tobacco.
i. Usually normal to low acid
levels; hyper acidity if
present is due to high
serum gastrin.
ii. ii. Damage to mucus
barrier is a significant
factor
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28. Features Duodenal ulcers Gastric ulcers
4. Pathological changes
5. Complication
i. Most common in the first
part of duodenum.
ii. Often solitary, 1-2.5 cm in
size, round to oval, punched
out.
iii. Histologically, composed of
4 layers necrotic, exudative,
granulation tissue and
cicatrisation
a. Haemorrhage,
b. Perforation,
a. Obstruction.
Most common along
the lesser curvature and
pyloric antrum.
ii. Grossly similar to duodenal
ulcers
iii. Histologically
indistinguishable from
duodenal ulcers
a. Haemorrhage,
b. Perforation,
c. Malignant transformation
in less than one % cases
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29. Features Duodenal ulcers Gastric ulcers
6. Clinical features a. Pain food relief pattern
b. Night pain common
c. No vomiting
d. Melaena more common
than haematemesis
e. No loss of weight
f. No particular choice of diet
fried foods, curries etc.
g. Marked seasonal variation
h. Occurs more commonly in
people at greater stress
a. Food pain pattern
b. No night pain
c. Vomiting common
d. Haematemesis more
common
e. Significant loss of weight
f. Deep tenderness in the mid
line of epigastrium
g. No seasonal variation
h. More often in labouring
groups
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