Peptic Ulcer Disease

Definitions

Ulcer:
A lesion on an epithelial surface (skin or mucous
membrane) caused by superficial loss of tissue

Erosion:
A lesion on an epithelial surface (skin or mucous
membrane) caused by superficial loss of tissue
which is limited to the mucosa.

Definitions

Peptic Ulcer
An ulcer of the alimentary tract mucosa,

?
e
r
he

Wstomach

duodenum
rarely in the lower esophagus

Structural Considerations

Mechanisms that maintain mucosal integrity

Gastric Mucosa & Secretions

The inside of the stomach is bathed in about two

liters of gastric juice every day.
Gastric juice is composed of digestive enzymes
and concentrated HCL , which can readily tear
apart the toughest food or microorganism.
The gastroduodenal mucosal integrity is
determined by protective (defensive) and
damaging (aggressive) factors.

Gastric Mucosa & Secretions

The defensive forces

Bicarbonate
Mucus layer
Mucosal blood flow
Prostaglandins
Growth factors

VS

The aggressive forces

Helicobacter pylori
HCl acid
Pepsins
NSAIDs
Bile acids
Ischemia and hypoxia.
Smoking and alcohol

Etiology

The two most common causes of PUD are:

Helicobacter pylori infection
Non-steroidal anti-inflammatory drugs (NSAIDS)

Other uncommon causes include:

Gastrinoma (Gastrin secreting tumor)

Stress ulceration (trauma, burns, critical illness)
Viral infections
Vascular insufficiency

Clinical Features
Gastric Ulcer
Duodenal Ulcer
Worse by/unrelated to 90 min 3 hr after
food
meal
Anorexia
>> Nocturnal
Weight Loss
Relieved by food
Food Aversion

1
2

Helicobacter pylori

Etiology Helicobacter pylori

Helicobacter pylori as a cause of PUD

The majority of PUD patients are H. pylori

infected.

Studies show that about 95% of patients with

DU and 85% with GU are infected with H.
pylori

Cure of H. pylori infection reduces ulcer

recurrence.

Etiology Helicobacter pylori

Helicobacter pylori as a cause of PUD

Over a 10 year period 1 out of 133 (0.75%)

individuals without H. pylori developed a peptic
ulcer, compared with 35 out of 321 (11%) with
H. pylori infection.

The incidence of peptic ulcers in H.pylori

infected people is about 1% per year.

1
6

Etiology NSAIDS

Etiology NSAIDs
Non-steroidal anti-inflammatory drugs
(NSAIDs)

Symptomatic GI ulceration occurs in 2% to 4%

of patients treated with NSAIDs for 1 year.

In view of the million of people who take NSAIDs

annually, these small percentages translate into
a large number of symptomatic ulcers.

The effects of aspirin and NSAIDs on the gastric

mucosa ranges from mucosal hemorrhages to
erosions and acute ulcers.

Etiology NSAIDS
Effect of NSAIDS

All NSAIDs reduce the mucosal production of

prostaglandins from precursor membrane fatty
acids.

The drugs also generate oxygen-free radicals and

products of the lipoxygenase pathway that may
contribute to ulceration.

Etiology NSAIDS

Users of NSAIDs are at approximately 3 times greater

relative risk of serious adverse gastrointestinal events
than nonusers.

Additional risk factors include:

Age greater than 60 years
Smoking
Previous history of GI events
Concomitant corticosteroid use. In terms of serious
complications, the combination of steroids and
NSAIDs leads to a 10-fold increase in GI bleeding
and a 20-fold increase in GI-related death.

Etiology NSAIDS
Type of NSAID and Risk of Ulcer
Risk Group Drug
Low Ibuprofen
Diclofenac 4.2

Relative Risk
2.0

Medium
Naproxen
Indomethacin
11.3
Piroxicam 13.7

9.1

High
Ketoprofen
Azapropazone
31.5

23.7

Etiology: NSAIDS + H. pylori

= ??

Are patients on NSAIDs who are also infected

with H. pylori more likely than those who are
not infected to have dyspepsia, mucosal
damage, or ulcers?

PUD Clinical Presentation

PUD Clinical Presentation

Symptoms of PUD

Pain
Epigastric pain
Hunger pain
Nocturnal pain

Other symptoms
Waterbrash
Heartburn
Vomiting

Asymptomatic
1% - 3% adults endoscopy volunteers
20% of complicated ulcers present without previous
symptoms

Peptic Ulcer Disease - Diagnosis

Diagnosis of ulcer
Diagnosis of H. pylori

Peptic Ulcer Disease - Diagnosis

Doudenal

Ulcer on Endoscopy

Normal doudenal
bulb

Doudenal Ulcer

Peptic Ulcer Disease - Diagnosis

Gastric

Ulcer on Endoscopy

Chronic Gastric Ulcers

Peptic Ulcer Disease - Diagnosis

Duodenal

Ulcer on Barium meal

Duodenal Ulcer

Peptic Ulcer Disease - Diagnosis

Gastric

Ulcer on Barium meal

Gastric Ulcer

Diagnosis of H. pylori
Tests for Helicobacter pylori
Non-invasive
C13 or C14 Urea Breath Test
Stool antigen test
H. pylori IgG titer (serology)
Invasive
Gastric mucosal biopsy
Rapid Urease test

Diagnosis of H. pylori
Tests for Helicobacter pylori
C13 or C14 Urea Breath Test

Diagnosis of H. pylori
Tests for Helicobacter pylori
Stool Antigen test

Diagnosis of H. pylori
Tests for Helicobacter pylori
Mucosal Biopsy

Diagnosis of H. pylori
Tests for Helicobacter pylori
Rapid Urease Test

This test is based on the

urease enzyme present in the
H. pylori

Urea is split into NH3 and CO2

The change in pH causes a

color change in the medium

PUD Complications

PUD Complications
Complications of PUD

Bleeding

Perforation

Gastric outlet or duodenal obstruction

Chronic anemia

Peptic Ulcer Disease Complications

Complications

of PUD on

Endoscopy

Bleeding DU
Duodenal stricture

Perforated GU

Peptic Ulcer Disease Treatment

Medical

Treatment
Endoscopic Treatment
Surgical Treatment

Peptic Ulcer Disease Treatment

Medical Treatment of Peptic Ulcer Disease

Pharmacologic intervention can speed healing of

peptic ulcers as well as delay and reduce the rate of
recurrent peptic ulceration.

The major aims of peptic ulcer therapy have been

expanded accordingly to include:
Rapid symptom resolution
Effective ulcer healing
H. pylori eradication
Prevention of ulcer relapse

Peptic Ulcer Disease Treatment

Medical Treatment of Peptic Ulcer Disease

The major agents in the current armamentarium

against peptic ulcer disease are
H2-receptor antagonists
H+,K+-ATPase (acid/proton pump) inhibitors
Sucralfate
Antacids
Bismuth compounds

Peptic Ulcer Disease Treatment

Sites of Drug Action in PUD

Peptic Ulcer Disease Treatment

The Mechanism and side effects of various acid suppressive medications
Drug

Mechanism

Antacids

Common side effect

neutralize acid

Mg - diarrhea

Al - constipation
Ca constipation
H2 receptor

block histamine receptor

cytochrome 450 altered

antagonists

metabolism of drugs

Prostaglandins

agonist diarrhea, cramps,

H+/K+ ATPase

block acid pump hypergastrinemia

inhibitors

enterochromaffin cell

(ECL) hyperplasia

Sucrafate

coat ulcerated mucosa

constipation

abortion

Peptic Ulcer Disease Treatment

Misoprostol

Synthetic prostaglandin E1 analog

Inhibits gastric acid secretion

Protects the gastric mucosa

Increases bicarbonate and mucous production
Decreases pepsin levels during basal conditions

Used in prevention of NSAIDS induced gastric ulcers

Does not prevent development of duodenal ulcers

May also stimulate uterine contractions that may endanger pregnancy

PUD H. pylori Treatment

Regimen

Omeprazole
Clarithromycin
Amoxicillin

Dosage

Duration

20 mg BID

7 10 days

500 mg BID

7 10 days

1000 mg BID

7 10 days

Ranitidine bismuth citrate (RBC)

400 mg BID

Clarithromycin

500 mg BID

7 10 days

Amoxicillin

1000 mg BID

7 10 days

Bismuth subsalicylate

525 mg QID

Metronidazole

500 mg BID

14 days

Tetracycline

500 mg QID

14 days

14 days

28 days

Gastritis
Gastritis
Inflammation of the gastric mucosa caused by any
of several conditions, including infection
(Helicobacter pylori), drugs (NSAIDs, alcohol), and
autoimmune phenomena (atrophic gastritis).

Many cases are asymptomatic, but dyspepsia and

GI bleeding sometimes occur.

Diagnosis is by endoscopy.

Treatment is directed at the underlying cause but

often includes acid suppression and, for H. pylori
infection, antibiotics.

Gastritis