Peptic Ulcer Disease

Norman Jay T. Almeana

Outline
I. Gastric Anatomy and Physiology
A. Anatomy of the Stomach and Duodenum as
compromised by Peptic Ulcer
B. Tissue Layers and Histologic Anatomy of the
Stomach and Duodenum
C. Mucosal Defense Mechanism
II. Incidence of Peptic Disease
III. Etiology
A. Genetic Factors
B. Environmental Factors
IV. Pathogenesis
A. Helicobacter pylori B. NSAIDs
V. Pathophysiology of PUD

Outline
VI. Clinical Manifestation
A. Neonatal
B. Infants and Young Children
C. In older Children and Adolescents
VII. Gastric Ulcer
VIII. Duodenal Ulcer
IX. Diagnostic Modalities Used in PUD
XI. Principles of Management
X. Complications of PUD
XI. Surgery

Tissue Layers and Histologic Anatomy

of the Stomach and Duodenum
a. Mucosa
- Epithelium
- Lamina propria
- Muscularis mucosa
b. Submucosa
c. Muscularis externa

- Inner circular muscle layer

- Outer longitudinal

Mucosal Defense Mechanism

Incidence of PUD
Occur at any group
More common between ages 1218 years
Gastric Ulcer
Commonly encountered in
children 6 years
and below
Duodenal Ulcer /Gastric Ulcer
5x more than in older children and
adolescents

Etiology
I. Genetic Factors
- 3x more common in 1st degree relatives
- Genes responsible for ulcer predisposition
unknown
- Family clustering due to high rate of H.
pylori infection
- Previously thought genetic factors like
elevated serum Pepsinogen I and blood group
O may in fact confer susceptibility to H. pylori
infection leading to peptic ulcer disease.

Etiology
I.
.

Environmental Factors
Cigarette smoking
Leads to decreased prostaglandin concentration in gastric and duodenal
mucosa.
Inhibits duodenal mucosal bicarbonate secretion.
Increases gastric acidity and H. pylori proliferation
H. pylori produces urease so it can live in pH 1-2 and damage cells
Adversely affects healing
Alcohol intake
Few published data support the notion that alcohol ingestion is a strong
risk factor for PUD.
Wine and beer may be potent gastric acid secretagogues but their role in
PUD pathogenesis is dubious.
Alcohol has been shown to cause only superficial mucosal injury.
Mucosta new drug from Japan inspired by fish mucus, acts like a mucus to
protect GIT
Stress
Emotional stress alone does not appear to be sufficient to cause ulcers
although recent studies still suggest that it can exacerbate ulcer activity
Stress related mucosal erosive lesions may develop in setting of sepsis,
burns and ischemia secondary to hypoperfusion.

Etiology
I.
.

Environmental Factors
Cigarette smoking
Leads to decreased prostaglandin concentration in gastric and duodenal
mucosa.
Inhibits duodenal mucosal bicarbonate secretion.
Increases gastric acidity and H. pylori proliferation
H. pylori produces urease so it can live in pH 1-2 and damage cells
Adversely affects healing
Alcohol intake
Few published data support the notion that alcohol ingestion is a strong
risk factor for PUD.
Wine and beer may be potent gastric acid secretagogues but their role in
PUD pathogenesis is dubious.
Alcohol has been shown to cause only superficial mucosal injury.
Mucosta new drug from Japan inspired by fish mucus, acts like a mucus to
protect GIT
Stress
Emotional stress alone does not appear to be sufficient to cause ulcers
although recent studies still suggest that it can exacerbate ulcer activity
Stress related mucosal erosive lesions may develop in setting of sepsis,
burns and ischemia secondary to hypoperfusion.

Pathogenesis
Helicobacter pylori
3 forms: coccoid, tubular or flagellated;
coccoid and tubular are non-migratory.
Coccoid is more resistant to
medications.

Pathogenesis
Role of Helicobacter Pylori in PUD
A spiral shaped gram negative bacterium that resides within or beneath the gastric mucus layer, somewhat
protected from stomach acid.
Its potent urease activity hydrolyzes urea to ammonia and bicarbonate which makes it resistance to the
stomachs low pH environment.
95% of patients with DUs 60-90% of GUs are infected
Mechanisms of Pathogenecity
-Damage epithelial cell membranes due to:
Direct adherence of organisms to epithelial cells
(coagulase +s higher affinity for adherence)
Ammonia produced by the urease enzyme
Bacterial cytotoxins
Bacterial enzymes disrupt the protective mucus
barrier, rendering underlying mucosa
susceptible to acid injury
Damage resulting from local and systemic inflammatory response to infection.
- Development of active chronic gastritis
Infection causes increase gastric acid production by increase serum gastrin levelsexcessive acid damages
duodenal mucosaleading to duodenal gastric metaplasiawhich becomes infected with H. pylori leading
to duodenitis and eventual duodenal ulcer.
H. pylori is considered as type I carcinogen, gastric metaplasia mimic gastric malignancy, some develop
gastrocarcinoma

Pathogenesis
NSAIDS
Epithelial effects (due to prostaglandin depletion)
by inhibiting cyclooxygenase pathway
Increased HCI secretion
o Increased mucin secretion
o Decreased HCO3 secretion
o Decreased surface active phospholipid secretion
o Decreased epithelial cell proliferation
Direct toxicity on mucosa of the stomach and
duodenum

CLINICAL MANIFESTATION
Most Common Symptoms
Vague upper abdominal discomfort and
little of the pain food- relief pattern
GIT bleeding
Vomiting
Primary Ulcers 6x more frequent than
secondary ulcers
Duodenal Ulcers > gastric ulcer

Pathophysiological Abnormalities in Gastric Ulcer

Patients
- Decreased acid secretion and increased H back
diffusion.
- Chronic superficial and atrophic gastritis.
- Increased concentration of a bile acids and
pancreatic juice
in stomach (duodenogastric reflux)
- Delayed gastric emptying distention of antrum
gastrin
stimulation, drug of choice: domperidone
- Inappropriately decreased pyloric sphincter
pressure under basal conditions and response to
stimuli.
+

Pathophysiological Abnormalities in Duodenal Ulcer

Patients

- Increased parietal cell mass (H production)

- Increased sensitivity of parietal cells to
secretagogues
- Increased parietal cell stimulation by increased
gastrin
released
- Increased numbers of antral G cells
- Decreased sensitivity of parietal cells to
inhibitory factors
- Increased drive to secrete acid and pepsin
- Increased gastric emptying
+

Pathophysiological Abnormalities in Duodenal Ulcer

Patients

- Decreased pancreatic bicarbonate secretion

- Increased duodenal acid load
- Impaired duodenal mucosal synthesis of
prostaglandin
- Abnormalities in the following mucosal
defensive factors promote peptic ulceration.
Decreased
Decreased
Decreased
Decreased
Decreased

gastric mucus
bicarbonate ions
gastric epithelial cell layer
mucosal blood flow
prostaglandins

Reparative Process in Ulcer Healing

Ulcers heal by reepithelialization,
usually 4-8 weeks of therapy although
60% and 80-90% can heal
spontaneously in 1 and 2 years,
respectively.
An ulcer scar that is unstable can lead to
recurrence of the ulcer in the same site.

Typical Symptoms (Differentiating Between Duodenal

and Gastric Ulcers

Duodenal Ulcers
Sharp, burning, gnawing pain
May be ill-defined, boring, aching or
hunger-like Located in the epigastric area
- Rhythmic pain regularly relieved by
food, milk or antacids but returns 1.5 4
hours after eating
Awakens patient from sleep between
1:00 & 3:00 am (when peak of acid
secretion occur)

Gastric Ulcers
Classical pain is also rhythmic and periodic
Pain pattern is different from DU in rhythmicity Pain is
least or absent during fasting but occurs shortly after
eating (5-15 minutes) and remains until the stomach
empties, either naturally or by vomiting
Nocturnal occurrence of pain is less common Pain may
radiate posteriorly and to the L upper quadrant
Associated weight loss may be due to food avoidance
or reduction in dietary intake (to escape from pain)
Relieving effects of food intake may be due to
buffering effect of food

H. pylori Confirmation
a. Via endoscopy
Biopsy specimens are taken from the stomach (esp. from the
gastric antrum) and processed for:
Direct culture for H. pylori
Histologic staining
Urease Activity a biopsy specimen is placed on a
template containing urea and pH indicatorif H. pylori is
present, their urease hydrolyzes urea to bicarbonate and
ammonia, raising the pH and changing color of the pH
indicator: (>95% sensitivity & specificity)
note: Stomach antrum-no rugal fold when seen in
the endoscope

H. pylori Confirmation
b. Non-endoscopic Confirmation
1. Serology detects antibodies against H.pylori
- may remain elevated up to 3 years even after treatment,
therefore is not a good test to confirm eradication (>90%
sensitivity & specificity)
2. Urea Breath Test patient ingest a small amount of radiolabelled
urea.
- H. pyloris urease hydrolyzes the urea and liberates labeled CO
which is absorbed and exhaled in the breath; then collected and
quantified.
- positive only in active infection, therefore ideally suited to monitor
treatment response and assess reinfection. (>95% sensitivity and
specificity) -usually for follow-up so no need for repeat endoscopy

Principles of Management
Heal the ulcer primary aim
Relieve the pain
Prevent complications and
recurrence

DRUGS USED
Histamine H2 Receptor Antagonists (H2
RAs)
Inhibit acid secretion by blocking H2 receptors
on the gastric parietal cell
Cimetidine 400 mg BID or 800 mg at hs up to
1.2 g/day
Ranitidine 150 mg BID or 300 mg at hs
Famotidine 20 mg BID or 40 mg at hs
Nizatidine 150 mg BID or 300 mg at hs

DRUGS USED
Proton Pump inhibitors (PPIs)
Concentrated in the parietal cells where they bind with
the enzyme H+/K+ -ATPase, the final common
pathway of acid secretion
Induce profound long lasting inhibition of acid
secretion
Current PPIs
Omeprazole
Lansoprazole
Rabeprazole
Pantoprazole
Esomeprazole- most potent

DRUGS USED
Surface Coating Agents
Sucralfate
A complex metal salt of sulfated sucrose
Adheres to ulcer craters and forms a protective barrier
that may prevent further acid-peptic attack
Also enhances defensive factors of stomach
Bismuth
Forms complexes with mucus that appears to coat ulcer
craters, affording protection from acid-peptic attack