Peptic Ulcer Disease (PUD)

Definition of Peptic Ulcer Disease (PUD)

• PUD is chronic mucosal ulceration, primarily affecting the stomach and proximal duodenum.
• It develops from the action of gastric secretions on the GIT.
• Lesions are often solitary.

Locations of PUD

• Order of decreasing frequency: Duodenum (1st portion), stomach (usually antrum), GE junction (reflux/Barret esophagus), margins of gastrojejunostomy, within or adjacent to Meckel diverticulum with gastric heterotopic in the setting of ZE syndrome.

Common locations

• Distal stomach and proximal duodenum.

Risk Factors

• H. pylori infection
• NSAIDs
• Cigarette smoking
• Chronic obstructive pulmonary disease.
• Corticosteroids.
• Alcoholic cirrhosis.
• Psychological stress
• Cocaine use which reduces mucosal blood flow
• Endocrine cell hyperplasia
• Zollinger-Ellison syndrome
• Viral infections such as CMV.

Epidemiology

• The lifetime risk of developing PUD is approximately 10%.
• The incidence of PUD in adults is 0.2%.
• Postmortem series show a prevalence rate of 8.1% to 10.8%.

Age and Sex Distribution

• Peak incidence of duodenal ulcers occurs between 30 and 60 years but can occur in infants
• Gastric ulcers are more common in middle-aged and elderly individuals compare to young patients.
• Duodenal ulcers exhibit a shift from female to male predominance since the 19th century.
• The incidence of gastric ulcers is similar in men and women (1.5:2.1).

Racial Differences

• Duodenal ulcers are rare among blacks in Africa.
• The incidence is equal in blacks and whites in the U.S.

Etiopathogenesis: Environmental Factors

• Spicy food and caffeine do not significantly contribute to peptic ulcer development or persistence.
• Coffee and alcohol also do not significantly contribute.

Influence of Drugs and Smoking

• Aspirin, NSAIDs, and analgesics are contributing factors, especially for gastric ulcers.
• Prolonged corticosteroid treatment slightly increases the risk of ulcers.
• Cigarette smoking serves as a risk factor, notably for gastric ulcers

Genetic Predisposition

• First-degree relatives of patients with duodenal ulcers have a 3-fold increased risk.
• A similar increase does not translate to gastric ulcers.
• PUD incidence higher in monozygotic than dizygotic twins.
• Individuals with type O blood have a 30% higher duodenal ulcer risk.
• Gastric ulcer patients do not have a greater frequency of blood group O.

Pepsinogen I levels

• High circulating levels of pepsinogen I is a measure of parietal cell mass and increases duodenal ulcer risk by 5 times.

Hydrochloric Acid

• Gastric acid secretion is required for peptic ulcer formation.

Physiological Factors in Duodenal Ulcers

• Parietal cell mass and maximal acid secretion increased up to twofold in patients with duodenal ulcers.
• Accelerated gastric emptying causes excessive acidification of the duodenum.
• Acidic pH in the duodenal bulb is required for duodenal ulcer production.

Gastric Ulcers

• Gastric ulcers are associated with H. pylori or chemical gastritis.
• Most patients secrete less acid than normal individuals.

Factors implicated

• Back diffusion of acid into the mucosa
• Decreased parietal cell mass
• Abnormalities of parietal cells.

H. pylori's Role

• Isolated from the gastric antrum of nearly all duodenal ulcer patients.
• Duodenal ulcer disease is found among only a small minority of persons infected with H. pylori
• H. pylori is a condition is necessary, but not sufficient, for PUD development in the duodenum.

H.pylori and PUD

• Intense inflammatory and immune responses with increased products of pro-inflammatory cytokines e.g. IL-1, IL-6, IL-8, and TNF.
• It secretes urease to break down urea into toxic compounds like NH4Cl and monochloramine
• Elaborates phospholipases and proteases that break down glyprotein lipid complexes in the gastric mucus
• Enhances gastric acid secretion and impairs duodenal bicarbonate production, reducing pH

Bacterial Platelet Activating Factor

• Thrombotic occlusion of surface capillaries is promoted
• H. pylori colonization evoked with prodution of activated T cells and B-cells.

Cytotoxin-associated antigen (CagA)

• Over 80% of duodenal ulcer patients are infected by CagA positive strains.
• Infection with CagA positive strains results in more organisms in tissues
• Causes severe epithelial damage
• Leads to greater acute and chronic inflammation
• Results in higher peptic ulceration likelihood
• Has an increased risk for gastric cancer

Vacuolating toxin (VacA)

• VacA is a virulence factor of HP involved in the pathogenesis of ulcer.
• This toxin causes cell injury and gastric tissue damage
• It acts as passive urea transporter thereby increasing the permeability of the epithelium to urea
• Approximately 75% of gastric ulcer patients harbor H. pylori, while the remaining 25% are associated with chronic gastritis.

Diseases Associated with Peptic Ulcers

• Cirrhosis increases duodenal ulcer risk by 10 times.
• End-stage kidney disease with hemodialysis heightens peptic ulceration risk.
• Renal transplantation also contributes to this risk and complications.
• Alpha 1 antitrypsin deficiency: - About 1/3 of patients with disease have peptic ulcer
• Chronic pulmonary disease: - About ¼ of patients with long standing pulmonary disease have peptic ulcer disease - Chronic lung disease also increases 2-3 folds in persons with PUD

Morphology of Peptic Ulcers

• Most common in the proximal duodenum and lesser curvature of the stomach, antral and prepyloric region.

Gross Characteristics - Gastric Ulcers

• Usually single and less than 2cm in diameter.
• Lesser curvature ulcers commonly linked to chronic gastritis
• Greater curvature ulcers often linked to with NSAIDs
• Round to oval shaped sharply punched out defects
• Overhanging margins, unlike the heaped-up margins characteristic of cancer
• Deep ulcers make serosal exudate for stomach
• Scarring of ulcers is severe enough to produce pyloric stenosis
• On examination, difficult to distinguish from an ulcerated gastric carcinoma.

Characteristics - Duodenal Ulcers

• Located on the anterior and posterior wall of the first part of the duodenum, within a short distance of the pylorus
• Usually solitary, but can be paired ulcers on both walls (kissing ulcers).

Microscopic Characteristics in Both Type of Ulcers:

• From the lumen outward:
• Zone of fibrinopurulent exudates
• Necrotic tissue
• Granulation tissue
• Fibrotic tissue at the base

Other information:

• Ulceration penetrates the muscle layers, causing them to become interrupted by scar tissue
• Mucosa at the margins of the ulcer tends to be hyperplastic and with healing
• Epithelium single layer above ulcerated area
• Duodenal ulcers come with Brunner gland hyperplasia and gastric mucin cell metaplasia

Complications of PUD

• Hemorrhage in 20% of cases.
• Most common complication,
• Iron deficiency anemia manifestation
• Accounts for 25% of deaths. Bleeding might be the first sign of PUD.
• Perforation in 5% of cases and accounts for two thirds of ulcer deaths and the
• Pyloric Obstruction in 2% of chronic ulcer
• Malignant transformation of a benign gastric ulcer is a risk.
• Cancers from benign peptic ulcers account for fewer than 1% of all malignant tumors in the stomach.