Prepared by

PEPTIC ULCER DISEASE Darien Liew Daojuin

24 May 2017
OVERVIEW
The term peptic ulcer refers to an ulcer in the lower oesophagus,
stomach or duodenum, in the jejunum after surgical anastomosis to the
stomach or, rarely, in the ileum adjacent to a Meckels diverticulum.
Ulcers in the stomach or duodenum may be acute or chronic; both
penetrate the muscularis mucosae but the acute ulcer shows no
evidence of fibrosis.
Erosions do not penetrate the muscularis mucosae.
AETIOLOGY
Two most important
aetiology in PUD are H.
Pylori and NSAIDs.
PATHOGENESIS
PATHOGENESIS
GASTRIC VS. DUODENAL ULCER
Gastric ulcers mostly occur along the lesser curvature of the stomach,
in particular, at the transition from corpus to antrum mucosa.
Duodenal ulcers usually occur in the duodenal bulb, which is the area
most exposed to gastric acid.
PATHOGENESIS
H. PYLORI INFECTION

Around 90% of duodenal ulcer patients and 70% of gastric ulcer

patients are infected with H. pylori. The remaining 30% of gastric
ulcers are caused by NSAIDs and this proportion is increasing in
Western countries as a result of H. pylori eradication strategies.
PATHOGENESIS
H. PYLORI INFECTION
H. pylori is Gram-negative and spiral, and has multiple flagella at
one end, which make it motile, allowing it to burrow and live beneath
the mucus layer adherent to the epithelial surface.
It uses an adhesin molecule (BabA) to bind to the Lewis b antigen on
epithelial cells. Here the surface pH is close to neutral and any acidity
is buffered by the organisms production of the enzyme urease. This
produces ammonia from urea and raises the pH around the bacterium
and between its two cell membrane layers.
H. pylori exclusively colonises gastric-type epithelium and is only found
in the duodenum in association with patches of gastric metaplasia. It
causes chronic gastritis by provoking a local inflammatory response in
the underlying epithelium. This depends on numerous factors, notably
expression of bacterial cagA and vacA genes.
PATHOGENESIS
H. PYLORI INFECTION
The cagA gene product is injected
into epithelial cells, interacting with
numerous cell-signalling pathways
involved in cell replication and
apoptosis. 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,
which causes increased cell
permeability, efflux of micronutrients
from the epithelium, induction of
apoptosis and suppression of local
immune cell activity. Several forms of
vacA exist and pathology is most
strongly associated with the s1/ml
form of the toxin.
PATHOGENESIS
H. PYLORI INFECTION
In most people, H. pylori causes localised
antral gastritis
associated with depletion of somatostatin
(from D cells)
increased gastrin release from G cells
hypergastrinaemia stimulates increased acid
production by parietal cells but, in the
majority of cases, this has no clinical
consequences.

In 1% of infected people, H. pylori causes

a pangastritis, leading to gastric atrophy
and hypochlorhydria. This allows other
bacteria to proliferate within the stomach;
these produce mutagenic nitrites from
dietary nitrates, predisposing to the
development of gastric cancer
PATHOGENESIS
H. PYLORI INFECTION
 PATHOGENESIS
SEQUELAE OF H. PYLORI INFECTION
Although colonization with H. pylori is almost invariably associated with the
presence of gastritis, and gastritis is mostly due to H. pylori colonization, other
causes of gastritis include infections such as CMV, chronic idiopathic inflammatory
and autoimmune disorders such as Crohn's disease and pernicious anemia, and
chemical damage due to alcohol abuse or NSAIDs.

1 to 2% risk of
developing distal gastric
cancer

10%-20% lifetime risk of

developing ulcers
PATHOGENESIS OF GASTRODUODENAL TOXICITY

The pathogenesis of symptomatic peptic ulcer disease caused by repeated

exposure to NSAIDs is mainly a consequence of systemic (post-absorptive)
inhibition of gastrointestinal mucosal cyclo-oxygenase (COX) activity.

Aspirin and many other NSAIDs (e.g, ibuprofen, naproxen, indomethacin, and
ketorolac) are carboxylic acids. Their pKa values range from 3.50 (aspirin) to
4.85 (ibuprofen).
Not ionized at the acidic pH found in the gastric lumen and thus can be absorbed across the
gastric mucosa.
Once these drugs move forward into the pHneutral mucosa, the drugs ionize and are trapped
temporarily in epithelial cells where it may damage these cells.
PATHOGENESIS OF GASTRODUODENAL TOXICITY
ARACHIDONIC ACID PATHWAY
PATHOGENESIS OF GASTRODUODENAL TOXICITY
CENTRAL PROTECTIVE ROLE OF COX & PG

The healthy gastric and duodenal mucosa constitutively use COX-1 to

produce its mucosal-protective PGs.
Many NSAIDs are non-selective and block COX-1 and COX-2
impairing gastric PG production at low concentrations.
Examples include celecoxib, meloxicam, nabumetone and etodolac.

Selective inhibitors of COX-2 may preserve PG-mediated gastrointestinal mucosal

protection. However, COX-2 selective inhibitors may still block COX-1 in the stomach
and duodenum at clinically recommended doses and thus have the potential to cause
damage. Examples include celecoxib and etodolac.
CLINICAL PRESENTATION
Dyspepsia Upper abdominal pain or discomfort.
The "classic" pain of duodenal ulcers occurs two to five hours after a
meal when acid is secreted in the absence of a food buffer and at
night (between about 11 PM and 2 AM) when the circadian
stimulation of acid secretion is maximal.
Patients with peptic ulcers, and particularly pyloric channel ulcers, may
have food-provoked symptoms due to visceral sensitization and
gastroduodenal dysmotility. These symptoms include epigastric pain
that worsens with eating, postprandial belching and epigastric fullness,
early satiety, fatty food intolerance, nausea, and occasional vomiting
CLINICAL PRESENTATION
ULCER COMPLICATIONS
1. Bleeding Nausea, hematemesis
(either red blood or coffee-ground
emesis), or melena (black, tarry
stool). In rare cases, patients have
massive bleeding and present with
hematochezia (red or maroon blood
in the stool) and orthostatic
hypotension
2. Gastric outlet obstruction In cases
where ulcers are found in the
pyloric channel or duodenum.
Symptoms of gastric retention
include early satiety, bloating,
indigestion, anorexia, nausea,
vomiting, epigastric pain shortly
after eating, and weight loss
CLINICAL PRESENTATION
ULCER COMPLICATIONS
3. Penetration and fistulization Patients with penetrating ulcers
often present with a change in symptoms (gradual or sudden) due
to symptomatic involvement of adjacent structures. The pain
typically becomes more intense, of longer duration, and is
frequently referred to the lower thoracic or upper lumbar spine
region. Penetrating posterior ulcers classically present with a shift
from the typical vague visceral discomfort to a more localized and
intense pain that is felt in the back and is not relieved by food or
antacids. E.g. gastrocolic, duodenocolic fistulas.
4. Perforation Suspected in patients who suddenly develop severe,
diffuse abdominal pain.
APPROACH TO PATIENTS WITH DYSPEPSIA
According to the Rome IV criteria,
dyspepsia is defined as one or more of
the following symptoms:
Postprandial fullness (classified as
postprandial distress syndrome)
Early satiation (inability to finish a normal
sized meal, also classified as postprandial
distress syndrome)
Epigastric pain or burning (classified as
epigastric pain syndrome)
DIAGNOSIS
MALIGNANT SUSPICION
Some endoscopic features that suggest that an ulcer may be
malignant include:
An ulcerated mass protruding into the lumen (heaped up appearance)
Folds surrounding the ulcer crater are nodular, clubbed, fused, or stop short of the
ulcer margin
Overhanging, irregular, or thickened ulcer margins.

Biopsy is indicated when

There is an ulcers with malignant features
There is duodenal involvement due to Crohn disease.
Management Algorithm
PPI, clarithromycin
and Amoxicillin
should be given
twice daily.
Metronidazole 3
times daily.
Triple therapy is
given for 14
days.
REFERENCE
UpToDate
https://www-uptodate-com.ezproxy.lib.monash.edu.au/contents/approach-to-the-
adult-with-dyspepsia?source=related_link#H75708801
https://www-uptodate-com.ezproxy.lib.monash.edu.au/contents/unusual-causes-of-
peptic-ulcer-disease?source=see_link#H11
https://www-uptodate-com.ezproxy.lib.monash.edu.au/contents/nsaids-including-
aspirin-pathogenesis-of-gastroduodenal-toxicity?source=see_link
https://www-uptodate-com.ezproxy.lib.monash.edu.au/contents/overview-of-the-
complications-of-peptic-ulcer-disease?source=see_link#H56805165
https://www-uptodate-com.ezproxy.lib.monash.edu.au/contents/indications-and-
diagnostic-tests-for-helicobacter-pylori-infection?source=related_link
https://www-uptodate-com.ezproxy.lib.monash.edu.au/contents/treatment-regimens-
for-helicobacter-pylori?source=see_link
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