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 UlcerAn ulcer of the alimentary tract mucosa,

stomach duodenumrarely in the lower esophagus

Where ?

Structural Considerations

Mechanisms that maintain mucosal integrity

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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

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The defensive forces– Bicarbonate– Mucus layer– Mucosal blood flow– Prostaglandins– Growth factors

Gastric Mucosa & Secretions

The aggressive forces– Helicobacter pylori– HCl acid– Pepsins– NSAIDs– Bile acids– Ischemia and hypoxia. – Smoking and alcohol

VS

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

Etiology

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Clinical Features

Gastric Ulcer• Worse by/unrelated to

food• Anorexia• Weight Loss• Food Aversion

Duodenal Ulcer• 90 min – 3 hr after

meal• >> Nocturnal• Relieved by food

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.

Etiology – Helicobacter pylori

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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

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 Relative Risk

Low Ibuprofen 2.0Diclofenac 4.2

Medium Naproxen 9.1Indomethacin 11.3Piroxicam 13.7

High Ketoprofen 23.7Azapropazone 31.5

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

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

PUD – Clinical Presentation

Peptic Ulcer Disease - Diagnosis

Diagnosis of ulcer Diagnosis of H. pylori

Doudenal Ulcer on Endoscopy

Normal doudenal bulb

Doudenal Ulcer

Peptic Ulcer Disease - Diagnosis

Gastric Ulcer on Endoscopy

Peptic Ulcer Disease - Diagnosis

Chronic Gastric Ulcers

Duodenal Ulcer on Barium meal

Peptic Ulcer Disease - Diagnosis

Duodenal Ulcer

Gastric Ulcer on Barium meal

Peptic Ulcer Disease - Diagnosis

Gastric Ulcer

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

Diagnosis of H. pylori

PUD – Complications

Complications of PUD

Bleeding

Perforation

Gastric outlet or duodenal obstruction

Chronic anemia

PUD – Complications

Complications of PUD on Endoscopy

Peptic Ulcer Disease - Complications

Bleeding DU Perforated GU Duodenal stricture

Peptic Ulcer Disease - Treatment

Medical Treatment Endoscopic Treatment Surgical 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

Peptic Ulcer Disease - Treatment

Sites of Drug Action in PUD

The Mechanism and side effects of various acid suppressive medications

Drug Mechanism Common side effect

Antacids neutralize acid Mg - diarrhea

Al - constipation

Ca – constipation

H2 receptor block histamine receptor cytochrome 450 altered

antagonists metabolism of drugs

Prostaglandins agonist diarrhea, cramps, abortion

H+/K+ ATPase block acid pump hypergastrinemia

inhibitors enterochromaffin cell (ECL) hyperplasia

Sucrafate coat ulcerated mucosa constipation

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

Peptic Ulcer Disease - Treatment

Regimen Dosage Duration

Omeprazole 20 mg BID 7 – 10 days

Clarithromycin 500 mg BID 7 – 10 days

Amoxicillin 1000 mg BID 7 – 10 days

Ranitidine bismuth citrate (RBC) 400 mg BID 28 days

Clarithromycin 500 mg BID 7 – 10 days

Amoxicillin 1000 mg BID 7 – 10 days

Bismuth subsalicylate 525 mg QID 14 days

Metronidazole 500 mg BID 14 days

Tetracycline 500 mg QID 14 days

PUD – H. pylori Treatment

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