Peptic ulcer

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Peptic Ulcer Disease (PUD)

Definition

A peptic ulcer is an excoriated mucosal defect extending through the muscularis mucosae in any portion of the GI tract exposed to gastric acid and pepsin. Although the name implies pepsin, acid is the indispensable factor - peptic ulcers do not occur in its absence, and nearly all heal with proton pump inhibitors (PPIs). - Guyton & Hall Textbook of Medical Physiology; Bailey & Love's Short Practice of Surgery, 28e

Common Sites

Causes and most frequent locations of peptic ulcer, showing ulcer sites near the pylorus, lesser curve, and marginal ulcer site

Figure: Causes and common sites of peptic ulcer (Guyton & Hall)

Site	Notes
First part of duodenum	Most common overall
Gastric antrum / lesser curve (incisura angularis)	Classic gastric ulcer location
Prepyloric / pyloric channel	Behaves like duodenal ulcer; must biopsy
Oesophagus (lower)	Due to acid reflux
Meckel's diverticulum	Contains ectopic gastric mucosa
Stomal (marginal) ulcer	After gastroenterostomy or Billroth II

Bailey & Love's Short Practice of Surgery, 28e; Guyton & Hall

Epidemiology

Over 4 million individuals in the US are treated each year
Lifetime risk: ~10% in males, ~4% in females
Duodenal ulcers are ~4x more common than gastric ulcers
Incidence is declining in resource-rich countries (due to H. pylori eradication) but rising in resource-poor nations
Peak incidence has shifted to older age groups; gender gap is narrowing
Robbins & Kumar Basic Pathology; Bailey & Love, 28e

Pathophysiology - The Balance Concept

PUD results from an imbalance between damaging and protective forces:

Protective factors:

Mucus gel layer (secreted by mucous neck glands)
HCO₃⁻ secretion trapped within mucus (neutralizes any H⁺ that penetrates)
Prostaglandin E₂ (stimulates HCO₃⁻ secretion, maintains mucosal blood flow)
Mucosal blood flow and growth factors
Pancreatic bicarbonate (neutralizes acid in duodenum)
Brunner glands (alkaline mucus in proximal duodenum)

Damaging factors:

H⁺ and pepsin (always required)
Helicobacter pylori infection
NSAIDs (suppress prostaglandin synthesis, impair barrier)
Smoking (reduces mucosal blood flow, delays healing)
Alcohol, stress, corticosteroids
Costanzo Physiology, 7e; Robbins & Kumar Basic Pathology

Aetiology

1. Helicobacter pylori

Responsible for >70% of PUD cases overall; >90% of duodenal ulcers
Gram-negative bacterium that colonises gastric mucus (especially the antrum)
Survives in the acid environment via urease - converts urea to NH₃, alkalinising its local environment
Releases cytotoxins (e.g., CagA toxin) that disrupt the mucous barrier and damage epithelial cells
NH₄⁺ (in equilibrium with NH₃) is directly cytotoxic
Diagnostic basis of the ¹³C-urea breath test: patient drinks ¹³C-urea → converted to ¹³CO₂ by urease → detected in exhaled breath
Only 5-10% of infected individuals develop ulcers, so host factors and strain variation (CagA-positive strains are more virulent) also matter
Costanzo Physiology, 7e; Robbins & Kumar Basic Pathology

2. NSAIDs

Inhibit COX enzymes → suppress prostaglandin synthesis → loss of mucosal protection and HCO₃⁻ secretion
Now the most common cause of gastric ulcers in Western countries as H. pylori rates fall, while low-dose aspirin use in older adults increases
Robbins & Kumar Basic Pathology

3. Zollinger-Ellison Syndrome

Gastrin-secreting tumour (gastrinoma) → massive acid hypersecretion
Causes multiple ulcers in stomach, duodenum, and even jejunum
In this syndrome, acid is essentially the sole aetiological factor
Robbins & Kumar Basic Pathology; Bailey & Love, 28e

4. Other Risk Factors

Cigarette smoking (increased relapse rate)
Alcohol-related cirrhosis, COPD, chronic renal failure, hyperparathyroidism
Hypercalcaemia (stimulates gastrin → increases acid secretion)
High-dose corticosteroids

Morphology (Pathology)

Chronic ulcers penetrate the mucosa into the muscularis propria, leading to fibrosis
Gastric ulcers tend to be larger than duodenal ulcers
Gastric ulcers: most common on lesser curve at the incisura angularis (boundary between acid-secreting and non-acid-secreting epithelia)
Duodenal: most common in the first part; "kissing ulcers" = simultaneous anterior and posterior ulcers (anterior tend to perforate, posterior tend to bleed from the gastroduodenal artery)
Fibrosis from chronic ulcers can cause pyloric stenosis or "hourglass" deformity of the stomach
Chronic gastric ulcers may erode posteriorly into the pancreas or splenic artery
Bailey & Love, 28e

Clinical Features

Gastric and duodenal ulcers are clinically indistinguishable by symptoms alone.

Epigastric pain: gnawing or burning in character, sometimes radiating to the back
Pain may be relieved by eating (especially duodenal) or worsened by food (gastric)
Intermittent course with periods of remission - this periodicity reflects spontaneous healing cycles
Vomiting: not prominent unless gastric outlet obstruction occurs
Weight loss (gastric ulcers often present with weight loss)
Bleeding: chronic blood loss → microcytic anaemia; acute = haematemesis ± melaena
Examination: epigastric tenderness; succussion splash if gastric outlet obstruction
Bailey & Love, 28e

Investigations

Endoscopy (Gastroduodenoscopy) - Gold Standard

Endoscopic view of a duodenal ulcer showing a white-based lesion in the duodenum

Figure: Duodenal ulcer at gastroduodenoscopy (Bailey & Love, 28e)

Allows direct visualisation, biopsy, and therapeutic intervention
All gastric ulcers must be biopsied (multiple biopsies) to exclude malignancy, regardless of appearance
Antral biopsies + CLO (Campylobacter-like organism) test for H. pylori
Duodenal ulcers: biopsy not mandatory for malignancy (duodenal ulcer = almost never malignant), but H. pylori testing should be done

H. pylori Testing

Test	Type	Notes
¹³C-urea breath test	Non-invasive	High sensitivity/specificity; used for diagnosis + post-treatment
Stool antigen test	Non-invasive	Equally accurate
CLO (urease) test	Endoscopic	Rapid, done at endoscopy
Serology	Blood	Cannot confirm active infection or eradication
Histology	Endoscopic	Gold standard for tissue diagnosis

Barium Meal

Now largely replaced by endoscopy
Duodenal ulcer: "niche" sign; gastric ulcer: seen on lesser curve with radiating folds
Useful where endoscopy not available

Other Tests

FBC (anaemia), urea and electrolytes
Fasting gastrin level if Zollinger-Ellison suspected

Treatment

1. Acid Suppression

Proton pump inhibitors (PPIs): first-line for all peptic ulcers; render patients virtually achlorhydric; standard dose for 4-8 weeks
H₂ receptor antagonists: less potent than PPIs; used as adjuncts or alternatives
Antacids: symptom relief only

2. H. pylori Eradication

The cornerstone of treatment for H. pylori-positive ulcers. Standard regimens:

Triple therapy: PPI + clarithromycin + amoxicillin (or metronidazole) for 7-14 days
Quadruple therapy (bismuth-based): PPI + bismuth + tetracycline + metronidazole - used where clarithromycin resistance is high or after first-line failure
Rising antibiotic resistance (especially to clarithromycin and levofloxacin) has complicated eradication, per 2024 ACG guidelines

Recent evidence: A 2024 systematic review with meta-analysis (PMID 39294424) found that vonoprazan (a potassium-competitive acid blocker) is superior to PPIs for both treatment and prevention of gastric/duodenal ulcers, representing an emerging alternative to standard PPI-based regimens.

A 2025 Cochrane review (PMID 40337979) confirmed that PPIs effectively prevent NSAID-induced ulcers and dyspepsia.

3. NSAID-Induced Ulcers

Stop the NSAID if possible
PPI co-prescription if NSAID cannot be stopped
Switch to selective COX-2 inhibitor (lower ulcer risk, though not zero)

4. Lifestyle Measures

Stop smoking (reduces relapse rate)
Avoid alcohol excess
Avoid NSAIDs and aspirin where possible

5. Surgery

Surgery is now very rarely required for uncomplicated PUD. Indications:

Failure of medical therapy
Complications (perforation, uncontrolled bleeding, obstruction)
Suspected malignancy

Complications

Complication	Key Points
Bleeding	Most common complication; posterior duodenal ulcers erode the gastroduodenal artery; assessed by Rockall score; endoscopic therapy first-line
Perforation	Anterior duodenal ulcers most often perforate; presents with sudden-onset peritonitis; primarily surgical (laparoscopic Graham patch repair)
Gastric outlet obstruction	Fibrosis → pyloric stenosis; presents with vomiting, succussion splash; balloon dilation or surgery
Malignant transformation	Rare in gastric ulcers; virtually never in duodenal ulcers; always biopsy gastric ulcers
Penetration	Erosion into adjacent organs (pancreas, splenic artery, colon)

Gastric vs. Duodenal Ulcer - Comparison

Feature	Gastric Ulcer	Duodenal Ulcer
Relative frequency	Less common	More common (~4x)
Acid secretion	Normal or low	Often elevated
Pain and food	Pain may worsen with food	Food often relieves pain
Malignancy risk	Present - always biopsy	Virtually nil
H. pylori association	Common	Very common (>90%)
Typical site	Lesser curve, incisura angularis	First part of duodenum
Posterior erosion risk	Splenic artery, pancreas	Gastroduodenal artery (bleeding)
Anterior perforation	Less common	Common ("anterior perforate, posterior bleed")

Sources:

Robbins & Kumar Basic Pathology, p. 3901-3909
Guyton & Hall Textbook of Medical Physiology, p. 825
Bailey & Love's Short Practice of Surgery, 28e, p. 1178-1180
Costanzo Physiology, 7e, p. 370
Sleisenger & Fordtran's Gastrointestinal and Liver Disease
PMID 39294424 - Vonoprazan vs PPIs meta-analysis (2024)
PMID 40337979 - Cochrane review: PPIs for NSAID-induced ulcers (2025)

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