PEPTIC ULCER

Dr Peltec Angela
DEFINITION
DEFINITION

 Peptic ulcers are defects in the gastric or

duodenal mucosa that extend through the
muscularis mucosa
 Peptic ulcers occur in those portions of the GI
tract that could be exposed to gastric secretions
containing pepsin
 That is a disease that have possibility to
recurrence
EPIDEMIOLOGY
EPIDEMIOLOGY
 The incidence of duodenal ulcers has been
decreasing over the past 3-4 decades
 Although the rate of simple gastric ulcer is in
decline, the incidence of complicated gastric
ulcer and hospitalization has remained
stable, partly due to the concomitant use of
aspirin in an aging population
 The prevalence of PUD has shifted from
predominance in males to similar occurrences in
males and females
 Age trends for ulcer occurrence reveal declining
rates in younger men, particularly for duodenal
ulcer, and increasing rates in older women
EPIDEMIOLOGY
 The frequency of PUD in other countries is variable and
is determined primarily by association with the major
causes of PUD: H pylori and NSAIDs
Epidemiologic studies reflect the
widespread incidence of Hp positive gastritis
ETIOLOGY
ETIOLOGY
Peptic ulcer disease (PUD) may be due to any of the
following:
 H pylori infection

 Drugs

 Lifestyle factors

 Severe physiologic stress

 Hypersecretory states (uncommon)

 Genetic factors
ETIOLOGY
H pylori infection
 H pylori infection and NSAID use account for
most cases of PUD
 90% of duodenal ulcers and 63% of gastric ulcers
were positive for H pylori
Drugs
 As many as 30% of adults taking NSAIDs have
GI adverse effects
 NSAI drugs disrupt the mucosal permeability
barrier and rendering the mucosa vulnerable to
injury
ETIOLOGY
LIFESTYLE FACTORS
 Smoking in the setting of H pylori infection may
increase the risk of relapse of PUD (smoking
may accelerate gastric emptying and decrease
pancreatic bicarbonate production)
 H pylori infiltration is denser in the gastric
antrum of smokers
 Ethanol is known to cause gastric mucosal
irritation and nonspecific gastritis
 Little evidence suggests that caffeine intake is
associated with an increased risk of duodenal
ulcers
ETIOLOGY
SEVERE PHYSIOLOGIC STRESS

Stressful conditions that may cause

PUD include:
burns
CNS trauma
surgery
severe medical illness (sepsis, hypotension,
respiratory failure, multiple traumatic injuries)
ETIOLOGY
HYPERSECRETORY STATES (UNCOMMON)

The following condition may, uncommonly, cause

PUD:
 Gastrinoma (Zollinger-Ellison syndrome) or
multiple endocrine neoplasia type I (MEN-I)
 Antral G cell hyperplasia

 Systemic mastocytosis

 Basophilic leukemias

 Cystic fibrosis

 Short bowel syndrome

 Hyperparathyroidism
ETIOLOGY
PHYSIOLOGIC FACTORS
 In up to one third of patients with duodenal
ulcers, basal acid output (BAO) and maximal
acid output (MAO) are increased
 The increased BAO may reflect the fact that in a
significant proportion of patients with
duodenal ulcers, the parietal cell mass is
increased to nearly twice that of the reference
range
 Acidification of the duodenum leads to gastric
metaplasia, which indicates replacement of
duodenal villous cells with gastric epithelium
 Gastric metaplasia may create an environment that
is well suited to colonization by H pylori
ETIOLOGY
GENETICS
 More than 20% of patients have a family history
of duodenal ulcers, compared with only 5-10% in
the control groups
 In addition, weak associations have been
observed between duodenal ulcers and blood type
O (do not secrete ABO antigens in their saliva)
 A rare genetic association exists between
familial hyperpepsinogenemia type I (a
genetic phenotype leading to enhanced secretion
of pepsin) and duodenal ulcers
PATHOPHYSIOLOGY
 PATHOPHYSIOLOGY

(A) HEALTHY GASTRIC MUCOSA: BALANCE (B) GASTRIC ULCER FORMATION:

BETWEEN MUCOSAL AGGRESSIVE AND IMBALANCE BETWEEN
PROTECTIVE FACTORS MUCOSAL AGGRESSIVE AND
PROTECTIVE FACTORS.
PATHOPHYSIOLOGY
PROTECTIVE FACTORS

The defensive mechanisms include

 mucus

 tight intercellular junctions

 cellular restitution

 epithelial renewal

 mucosal blood flow

PATHOPHYSIOLOGY
PROTECTIVE FACTORS
PREEPITHELIAL
 Mucus secreted by the epithelial cells of the
stomach and duodenum in response to irritation of
the epithelial lining and as a result of cholinergic
stimulation
 The superficial portion of the gastric and duodenal
mucosa exists in the form of a gel layer, which is
impermeable to acid and pepsin
 Other gastric and duodenal cells secrete
bicarbonate, which aids in buffering acid that lies
near the mucosa
 Prostaglandins of the E type (PGE) have an
important protective role, because PGE increases the
production of both bicarbonate and the mucous layer
PATHOPHYSIOLOGY
PROTECTIVE FACTORS
EPITHELIAL AND SUBEPITHELIAL

 Ion pumps in the basolateral

epithelial cell membrane help to
regulate intracellular pH by removing
excess hydrogen ions
 Through the process of restitution,
healthy cells migrate to the site of injury
 Mucosal blood flow removes acid that
diffuses through the injured mucosa and
provides bicarbonate to the surface
epithelial cells
PATHOPHYSIOLOGY
AGGRESSIVE FACTORS
 NSAIDs
 H pylori infection

 Alcohol

 bile salts

 Acid

 Pepsin

can alter the mucosal defense by allowing back

diffusion of hydrogen ions and subsequent
epithelial cell injury
PATHOPHYSIOLOGY
H PYLORI
 The gram-negative spirochete H pylori was
first linked to gastritis in 1983
 H pylori (Hp), acid and pepsin - contributes to
primary peptic ulcer disease
 Microbiologic characteristics of Hp is urease
production, allows it to alkalinize its
microenvironment and survive for years in the
hostile acidic environment of the stomach
 Hp has passed through the mucous layer, and
has become established at the luminal surface of
the stomach, an intense inflammatory response
of the underlying tissue develops
 PATHOPHYSIOLOGY
H. PYLORI
 The interaction of H
pylori with the surface
mucosa results in the
release of
proinflammatory
cytokine interleukin
(IL)-8, which leads to
recruitment of
polymorphonuclear cells
and may begin the entire
inflammatory process
 PATHOPHYSIOLOGY
H. PYLORI
 Antral inflammation alters the interplay between
gastrin and somatostatin secretion

 Infection with H. pylori may stimulate gastric acid

secretion by inhibiting the D-cell (somatostatin-
secreting cells) activity or inhibits this secretion by
direct impairment of the parietal cells

 Gastrin secretion (by G cells) is abnormal in

individuals who are infected with H pylori, with an
exaggerated meal-stimulated release of gastrin
being the most prominent abnormality
PATHOPHYSIOLOGY
H. PYLORI

inhibiting the D-cell

(somatostatin-
secreting cells)
activity
CLINICAL PRESENTATION
COMPLAINS
PAIN SYNDROME
Epigastric pain is the most common symptom of
both gastric and duodenal ulcers
It is characterized by
 Localization – epigastric area

 a gnawing or burning sensation

 occurs shortly after meals with gastric ulcer

and
 2-3 hours after meal with duodenal ulcer

 food or antacids relieve the pain of duodenal

ulcers, but provide minimal relief of gastric ulcer
pain
COMPLAINS

 Duodenal ulcer pain often awakens the

patient at night
 Pain with radiation to the back is suggestive
of a posterior penetrating gastric ulcer
complicated by pancreatitis
 Patients who develop gastric outlet
obstruction as a result of a chronic, untreated
duodenal ulcer usually report a history of
fullness and bloating associated with nausea
and emesis that occurs several hours after food
intake
COMPLAINS
Other possible manifestations include the
following:
 Dyspepsia

 Heartburn

 Chest discomfort

 Hematemesis or melena resulting from

gastrointestinal bleeding
ALARM SIMPTOMS

Alarm features that warrant prompt

gastroenterology referral include the following:
 Bleeding or anemia

 Early satiety

 Unexplained weight loss

 Progressive dysphagia or odynophagia

 Recurrent vomiting

 Family history of GI cancer

PHYSICAL EXAMINATION
In uncomplicated PUD, the clinical findings are few
and nonspecific and include the following:
 Epigastric tenderness (usually mild)

 Right upper quadrant tenderness may

suggest a biliary etiology or, less frequently, PUD
 Guaiac-positive stool resulting from occult
blood loss
 Melena resulting from acute or subacute
gastrointestinal bleeding
 Succussion splash resulting from partial or
complete gastric outlet obstruction
WORKUP
APPROACH CONSIDERATIONS
If the diagnosis of PUD is suspected, obtaining
 CBC count

 liver function tests (LFTs)

 Amylase

 lipase may be useful

 CBC count and iron studies can help detect

anemia, which is an alarm signal that mandates
early endoscopy to rule out other sources of
chronic GI blood loss
RADIOGRAPHY
 In patients presenting acutely, a chest
radiograph may be useful to detect free
abdominal air when perforation is suspected
 On upper GI contrast study with water-soluble
contrast, the extravasation of contrast indicates
gastric perforation
 Double-contrast radiography performed by an
experienced radiologist may approach the
diagnostic accuracy of upper GI endoscopy
 An upper GI series is not as sensitive as
endoscopy for establishing a diagnosis of small
ulcers (< 0.5 cm)
ENDOSCOPY
 Upper GI endoscopy is the preferred diagnostic
test in the evaluation of patients with suspected
PUD
 It is highly sensitive for the diagnosis of gastric
and duodenal ulcers, allows for biopsies and
cytologic brushings in the setting of a gastric
ulcer to differentiate a benign ulcer from a
malignant lesion, and allows for the detection
of H pylori infection with antral biopsies for a
rapid urease test and/or histopathology in
patients with PUD
 ENDOSCOPY
Gastric ulcer with punched-out Gastric ulcer (lesser curvature) with
ulcer base with whitish fibrinoid punched-out ulcer base with whitish
exudates exudate
BIOPSY
 A single biopsy offers 70% accuracy in diagnosing
gastric cancer, but 7 biopsy samples obtained
from the base and ulcer margins increase the
sensitivity to 99%
 Brush cytology has been shown to increase the
biopsy yield, and this method may be useful
particularly when bleeding is a concern in a
patient with coagulopathy
H PYLORI TESTING

Endoscopic or invasive
tests for H pylori include
a rapid urease test
histopathology
culture
 H PYLORI TESTING
Rapid urease tests are considered
the endoscopic diagnostic test of
choice

 The presence of H pylori in gastric

mucosal biopsy specimens is
detected by testing for the bacterial
product urease
 Three kits (ie, CLOtest, Hp-fast,
Pyloritek) are commercially
available for H pylori testing, and
each contains a combination of a
urea substrate and a pH sensitive
indicator
 One or more gastric biopsy
specimens are placed in the rapid
urease test kit
 If H pylori is present, bacterial
urease converts urea to ammonia,
which changes the pH, resulting in
a color change
H PYLORI TESTING
Obtain histopathology,
often considered the
criterion standard to
establish a diagnosis
of H pylori infection , if
the rapid urease test
result is negative and a
high suspicion for H
pylori persists (presence
of a duodenal ulcer)
H PYLORI TESTING

Noninvasive tests for H

pylori include
Urea breath tests
Antibodies (immunoglobulin
G [IgG]) to H pylori
Fecal antigen testing
H PYLORI TESTING
Urea breath tests detect
active H pylori infection by
testing for the enzymatic
activity of bacterial urease.
 In the presence of urease
produced by H
pylori, labeled carbon
dioxide (heavy isotope,
carbon-13, or radioactive
isotope, carbon-14) is
produced in the stomach,
absorbed into the
bloodstream, diffused into
the lungs, and exhaled
H PYLORI TESTING
Antibodies
(immunoglobulin G
[IgG]) to H pylori can
be measured in
 Serum
 Plasma
 whole blood

Results with whole

blood tests obtained
from finger sticks are
less reliable
H PYLORI TESTING
Fecal antigen testing
identifies active H
pylori infection by
detecting the presence
of H pylori antigens in
stools
This test is more
accurate than antibody
testing and is less
expensive than urea
breath tests
CLASIFICATION
 TYPE OF GASTRIC/DUODENAL ULCERS
A. GU-I
Characteristics, In body of stomach, especially the inner
curvature.
 Chief problem - inadequate protective ability
 Acid hyposecretion: parietal cell mass
 Gastrin secretion: normal or increased
 Age: onset at 60-70 years
 Exogenous aggressive factors: aspirin, NSAIDS (PG
synthesis and mucosal permeability)
 Duodeno-gastric reflux: low pyloric sphincter pressure; low
pyloric contractile response to acid in duodenum; disruption
of gastric mucosal barrier
 Genetic factors
 Helicobacter pylori and NH3 production
 TYPE OF GASTRIC/DUODENAL ULCERS
B. GU-II/DU
Characteristics, In pyloric gland region of
stomach/duodenum
 Chief problem - excess acid and pepsin
 Acid hypersecretion: parietal cell mass; parietal cell
sensitivity to secretagogues
 Nocturnal acid hypersecretion
 Gastrin hypersecretion with meals
 Accelerated gastric emptying
 Impaired inhibition of acid secretion
 Impaired bicarbonate secretion
 Impaired duodenal mucosal defense
 Helicobacter pylori and NH3 production
 STAGE CLASSIFICATION OF GASTRIC
ULCER BY SAKITA-MIWA
The gastric ulcer are staged, by using of the endoscopic staging system of
Sakita, into 3 stages (active, healing, scarring) as follows.
Stages Manifestation
Active stage

The surrounding mucosa is edematously swollen and no

A1
regenerating epithelium is
seen endoscopically

The surrounding edema has decreased, the ulcer margin

is clear, and a slight amount of regenerating epithelium is
A2 seen in the ulcer margin. A red halo in the marginal zone
and a white slough circle in the ulcer margin are frequently
seen. Usually, converging mucosal folds can be followed
right up to the ulcer margin
 STAGE CLASSIFICATION OF GASTRIC
ULCER BY SAKITA-MIWA
Stages Manifestation
Healing stage

The white coating is becoming thin and the regenerating

epithelium is extending into the ulcer base. The gradient
between the ulcer margin and the ulcer floor is becoming
H1
flat. The ulcer crater is still evident and the margin of the
ulcer is sharp. The diameter of the mucosal defect is about
one-half to twothirds that of A1

The defect is smaller than in H1 and the regenerating

H2 epithelium covers most of the ulcer floor. The area of white
coating is about a quarter to one-third that of A1
 STAGE CLASSIFICATION OF GASTRIC
ULCER BY SAKITA-MIWA
Stages Manifestation
Scarring stage

The regenerating epithelium completely covers the floor of

ulcer. The white coating has disappeared. Initially, the
S1
regenerating region is markedly red. Upon close
observation, many capillaries can be seen. This is called
‘‘red scar’’

In several months to a few years, the redness is reduced to

S2
the color of the surrounding mucosa. This is called ‘‘white
scar’’
References:
Kaneko E, Hoshihara Y, Sakaki N, Harasawa S, Ashida K, Asaka M, Asaki S, Nakamura T, Kobayashi K, Kajiyama G, Ogawa N, Yao T, Muto Y, Nakazawa
S, Takemoto T. Peptic ulcer recurrence during maintenance therapy with H2-receptor antagonist following first-line therapy with proton pump inhibitor. J
Gastroenterol. 2000;35(11):824-31. [Medline]
Matsumoto S, Tsuji K, Shirahama S. Rebamipide enema therapy for left-sided ischemic colitis patients accompanied by ulcers: open label study. World J
Gastroenterol. 2008 Jul 7;14(25):4059-64. [Medline]
PROGNOSIS
 Most patients are treated successfully with
eradication of H pylori infection, avoidance of
NSAIDs, and the appropriate use of antisecretory
therapy
 Eradication of H pylori infection changes the
natural history of the disease, with a decrease
in the ulcer recurrence rate from 60-90% to
approximately 10-20%