Peptic Ulcer Disease

Peptic Ulcer Disease (PUD) – High‑Yield Study Guide for Medical Students

Definition

Peptic ulcer disease (PUD) is defined as a break in the gastric or duodenal mucosa that extends through the muscularis mucosae, typically occurring in areas exposed to acid and pepsin. It most commonly affects the duodenal bulb and the lesser curvature of the stomach. PUD results from an imbalance between mucosal defensive factors (mucus, bicarbonate, prostaglandins, mucosal blood flow) and injurious factors (gastric acid, pepsin, Helicobacter pylori, NSAIDs).^[1]

Epidemiology

PUD remains a common cause of upper gastrointestinal morbidity worldwide, though incidence has decreased in many regions with declining H. pylori prevalence and better NSAID awareness.^[2]

• Prevalence: Approximately 5–10% lifetime risk globally, varying by region and risk factor burden.
• Geographic variation: High burden in regions with prevalent H. pylori infection (e.g., parts of Asia, including China) and high NSAID use.^[2]
• Age: Duodenal ulcers more common in younger to middle-aged adults; gastric ulcers more common in older adults.
• Sex: Historically more common in males, but sex gap is narrowing with increased NSAID use in both sexes.
• Trends: Decline in classic H. pylori-related ulcers but persistent burden of NSAID-associated and complicated ulcers (bleeding, perforation).^[2]

Etiology and Risk Factors

PUD is multifactorial, with two dominant etiologies: H. pylori infection and NSAID use. Additional factors increase susceptibility and severity.

• H. pylori infection
  • Major cause of duodenal and many gastric ulcers.
  • Promotes chronic active gastritis and mucosal damage.
  • Associated with higher risk of recurrent ulcers and gastric malignancy if untreated.^[2]
• NSAIDs and aspirin
  • Inhibit cyclooxygenase (COX-1 & COX-2), reducing prostaglandin synthesis.
  • Decrease mucosal blood flow, mucus and bicarbonate secretion, weakening mucosal defense.
  • Risk increases with dose, duration, age >65, concurrent steroids, anticoagulants, or antiplatelets.^[1]
• Physiologic stress
  • Critical illness, severe burns, trauma, sepsis, mechanical ventilation predispose to stress-related mucosal disease and stress ulcers, especially in ICU settings.^[3]
• Other contributing factors
  • Smoking, heavy alcohol use, corticosteroids (especially with NSAIDs), anticoagulants.
  • Hypersecretory states (e.g., Zollinger–Ellison syndrome).
  • Comorbidities like cirrhosis and CKD may increase complication risk.
  • Low vitamin D status has been associated with greater susceptibility to H. pylori-related gastric pathology, though causality is still being clarified.^[4]

Pathophysiology

PUD arises when gastric acid–pepsin activity overwhelms mucosal defenses in the stomach or duodenum.

• Normal defenses
  • Mucus–bicarbonate layer that neutralizes acid at the epithelial surface.
  • Prostaglandin-mediated mucosal blood flow and epithelial restitution.
  • Tight junctions and rapid epithelial cell turnover.
• H. pylori-mediated injury
  • H. pylori colonizes gastric mucosa, particularly the antrum, using urease to buffer acid and flagella to penetrate mucus.
  • It induces chronic active gastritis with inflammatory cytokine release and epithelial damage.
  • In antral-predominant infection, there is decreased somatostatin and increased gastrin, leading to increased acid secretion and duodenal ulceration.
  • In corpus-predominant infection, hypochlorhydria and atrophic gastritis can develop, associated more with gastric cancer risk.
• NSAID-induced injury
  • Systemic inhibition of COX-1 reduces protective prostaglandins, decreasing mucus and bicarbonate and impairing mucosal blood flow.
  • Topical irritant effect as weak acids that diffuse into epithelial cells and cause direct injury.
• Acid hypersecretion
  • In Zollinger–Ellison syndrome (gastrinoma), markedly elevated gastrin levels cause massive acid secretion, multiple refractory ulcers, and diarrhea.
  • Smoking and stress may modestly increase acid secretion and impair healing.
• Stress-related mucosal disease
  • In critically ill patients, splanchnic hypoperfusion and impaired mucosal defense lead to diffuse superficial erosions and ulcers, often in the fundus or body.^[3]

Clinical Presentation

Symptoms vary from classic epigastric pain to silent disease presenting only with complications such as bleeding or perforation.

• Typical symptoms
  • Epigastric pain (burning, gnawing, or aching) is the hallmark symptom.
  • Temporal relationship to meals:
    • Duodenal ulcer: Pain often occurs 2–3 hours after meals, may awaken patients at night, and is frequently relieved by food or antacids.
    • Gastric ulcer: Pain may be worsened by food and leads to fear of eating and weight loss.
  • Nausea, early satiety, bloating, or belching.
• Alarm features / red flags
  • Unintentional weight loss.
  • Recurrent or persistent vomiting.
  • Evidence of GI bleeding: hematemesis, melena, or iron deficiency anemia.
  • Dysphagia or odynophagia.
  • Family history of gastric cancer.
• Complicated presentations
  • Bleeding: Hematemesis, coffee-ground emesis, melena; may present with anemia, tachycardia, or hemodynamic instability.
  • Perforation: Sudden onset severe abdominal pain, rigid abdomen, signs of peritonitis; free air under diaphragm on imaging.^[5]
  • Penetration: Pain radiating to back, often from posterior duodenal or gastric ulcers eroding into adjacent organs.
  • Gastric outlet obstruction: Early satiety, postprandial vomiting, weight loss, succussion splash on exam.

Diagnostic Evaluation

The goal is to confirm the presence of an ulcer, identify the cause (H. pylori, NSAIDs, malignancy), and assess for complications.

Initial Assessment

• History: Character of pain, relation to meals, duration, NSAID/aspirin use, anticoagulants, steroids, smoking, alcohol, prior ulcers, family history.
• Physical exam: Epigastric tenderness, signs of anemia or hemodynamic compromise, peritonitis if perforated.

Role of Endoscopy

• Esophagogastroduodenoscopy (EGD) is the gold standard for diagnosing PUD.^[1]
• Allows direct visualization, documentation of ulcer characteristics (size, location, depth), targeted biopsies, and endoscopic therapy for bleeding.
• Indications for early endoscopy typically include:
  • Alarm features (weight loss, anemia, dysphagia, bleeding).
  • Age ≥ a region-specific threshold (often ≥60 years) with new dyspepsia.
  • Refractory or recurrent symptoms despite appropriate therapy.
  • Suspected complications (bleeding, perforation, obstruction).
• Gastric ulcers require biopsy to exclude malignancy and follow-up endoscopy to confirm healing.

Testing for H. pylori

All patients with documented PUD without clear NSAID-only etiology should be evaluated for H. pylori infection.^[1]

• Noninvasive tests
  • Urea breath test: Highly sensitive and specific; requires withholding PPIs (usually 2 weeks) and antibiotics (4 weeks) beforehand.
  • Stool antigen test: Also highly sensitive and specific; good for diagnosis and test-of-cure.
  • Serology: Detects antibodies; less favored due to inability to distinguish active from past infection.
• Invasive tests (via EGD)
  • Rapid urease test on gastric mucosal biopsies.
  • Histology with special stains.
  • Culture rarely used clinically but helpful for resistance testing in refractory cases.

Laboratory and Imaging

• Laboratory tests:
  • CBC for anemia or leukocytosis.
  • Basic metabolic panel to assess volume status and renal function.
  • Liver tests and coagulation profile in bleeding or cirrhosis.
  • Serum gastrin levels when suspecting Zollinger–Ellison syndrome (off PPIs).
• Imaging:
  • Upright chest or abdominal X-ray for free air if perforation suspected.
  • CT abdomen with contrast for complicated ulcers (perforation, abscess, penetration, peritonitis).^[5]

Management

Management has three core pillars: acid suppression, eradication of H. pylori when present, and elimination of exacerbating factors (especially NSAIDs). Treatment strategies should be individualized based on etiology, severity, and presence of complications.^[1]

General Principles

• Remove or reduce injurious agents (stop NSAIDs if possible, avoid smoking and heavy alcohol intake).
• Use adequate-dose proton pump inhibitors (PPIs) to suppress acid and promote healing.
• Treat H. pylori infection comprehensively and confirm eradication.
• Manage complications (bleeding, perforation, obstruction) promptly with endoscopic, medical, and sometimes surgical interventions.

Pharmacologic Therapy

• Proton pump inhibitors (PPIs)
  • First-line for ulcer healing: e.g., omeprazole, pantoprazole, esomeprazole, rabeprazole, lansoprazole.
  • Typical regimen: standard-dose PPI (e.g., omeprazole 20 mg PO BID) for 4–8 weeks; 8 weeks often used for gastric ulcers.
  • Superior to H2-receptor antagonists for acid suppression and healing rates.
• H2-receptor antagonists
  • Examples: ranitidine (where available), famotidine, nizatidine.
  • Less potent than PPIs but can be used in mild disease or when PPIs are contraindicated.
• Antacids and mucosal protectants
  • Antacids (aluminum/magnesium hydroxide) provide short-term symptomatic relief.
  • Sucralfate forms a protective barrier over ulcer bases and may be used particularly in stress-related mucosal disease.
  • Bismuth compounds provide mucosal protection and have anti-H. pylori activity and are integral to some eradication regimens.
• Prostaglandin analogs
  • Misoprostol (PGE1 analog) can reduce NSAID-induced gastric ulcers but is limited by diarrhea and cramping.
  • Useful in patients who must remain on NSAIDs and are at high GI risk, though PPIs are often preferred due to better tolerability.

H. pylori Eradication

Eradicating H. pylori is crucial to prevent recurrence, complications, and long-term gastric cancer risk.^[1]

• Principles
  • Use optimized multi-drug regimens based on local resistance patterns (many regions now favor bismuth-based quadruple therapy as first-line).
  • Typical duration: 10–14 days.
  • Avoid antibiotics to which local resistance is high (e.g., clarithromycin- or levofloxacin-based therapy only in appropriate settings).
• Example regimens (conceptual)
  • Bismuth quadruple therapy: PPI + bismuth + tetracycline + metronidazole.
  • Concomitant therapy: PPI + clarithromycin + amoxicillin + metronidazole.
• Test-of-cure
  • Required in all patients with ulcers to ensure eradication.
  • Use urea breath test or stool antigen test ≥4 weeks after completion of therapy and ≥2 weeks off PPIs.

Management of NSAID-Associated Ulcers

• Stop NSAIDs if at all possible; switch to alternative analgesics (e.g., acetaminophen, non-NSAID options).
• If NSAIDs must be continued:
  • Use the lowest effective dose and consider a COX-2 selective agent in selected patients.
  • Co-prescribe a daily PPI for gastroprotection.
  • Consider misoprostol in selected high-risk cases if tolerated.
• Always evaluate for coexisting H. pylori infection and eradicate if present.

Stress Ulcer Prophylaxis in Critically Ill Patients

Stress-related mucosal disease (SRMD) can cause clinically significant GI bleeding in high-risk ICU patients; targeted prophylaxis is recommended.^[3]

• Candidates for prophylaxis typically include:
  • Mechanical ventilation >48 hours.
  • Coagulopathy, severe burns, TBI, spinal cord injury, shock, or multiorgan failure.
• Agents
  • PPIs (e.g., IV pantoprazole) or H2 blockers (e.g., IV famotidine) are commonly used.
  • Sucralfate is an alternative when acid suppression is undesirable.
• Prophylaxis should be reassessed regularly and discontinued once risk resolves to minimize infection risks (e.g., pneumonia, C. difficile).

Management of Complications

Upper GI Bleeding

• Initial stabilization with IV fluids, blood transfusions as indicated, and correction of coagulopathy.
• High-dose IV PPI (e.g., bolus followed by continuous infusion) before and after endoscopy to stabilize clots.
• Urgent EGD for diagnosis and endoscopic hemostasis (injection therapy, thermal coagulation, hemoclips).
• Risk stratification using endoscopic stigmata (Forrest classification) and clinical scores guides post-endoscopic management.
• Recurrent or refractory bleeding may require repeat endoscopy, transcatheter arterial embolization, or surgery.^[1]

Perforation and Peritonitis

• Patients present with acute abdomen and generalized peritonitis; CT usually confirms perforation.^[5]
• Management
  • Hemodynamic resuscitation, broad-spectrum IV antibiotics.
  • Surgical repair (e.g., omental patch) is standard for most free perforations.
  • Laparoscopic vs open approaches chosen based on patient stability and local expertise.
  • In perforated peptic ulcer with peritonitis, fungal co-infection is not rare; empiric antifungal therapy remains controversial and is generally reserved for selected high-risk patients (e.g., immunocompromised, high-risk peritonitis).^[6]

Gastric Outlet Obstruction

• Often due to chronic scarring and edema from pyloric channel ulcers.
• Management includes nasogastric decompression, high-dose PPI, and endoscopic evaluation.
• Endoscopic balloon dilation may relieve benign obstruction; refractory cases may require surgery.

Prevention and Long-Term Management

• Eradicate H. pylori in all infected ulcer patients and confirm eradication.
• Minimize NSAID exposure:
  • Use lowest effective dose and shortest duration.
  • Co-prescribe PPIs in high-risk patients (prior ulcer, age >65, concomitant antiplatelets/anticoagulants).
• Lifestyle: Smoking cessation and moderation of alcohol use.
• Maintenance therapy:
  • Some high-risk patients (e.g., those with recurrent ulcers, ongoing NSAID/aspirin that cannot be stopped, or Zollinger–Ellison syndrome) may need long-term or intermittent PPI therapy.
• Follow-up endoscopy:
  • Recommended for gastric ulcers to confirm healing and exclude malignancy.
  • Not routinely required for uncomplicated duodenal ulcers if symptoms resolve.

Emerging and Complementary Therapies (Conceptual Overview)

There is growing interest in adjunctive and alternative therapies for PUD, particularly where conventional therapy is limited by resistance, adverse effects, or access.

• Complementary approaches
  • Studies have explored combinations such as acupuncture plus herbal medicine for gastric ulcers, showing potential benefit in symptom relief and healing rates, though data quality is variable and these are not standard first-line therapies.^[7]
  • A broad range of plant extracts and phytochemicals with antioxidant, anti-inflammatory, and mucosal-protective properties are under investigation for anti-ulcer effects, but robust clinical evidence is still limited.^[8]
• For examination purposes, emphasize standard evidence-based therapies (PPIs, H. pylori eradication, NSAID modification). Complementary modalities remain adjunctive and experimental.

Key Clinical Pearls for Exams and Practice

• Duodenal vs gastric ulcer
  • Duodenal: pain relieved by food, more common with H. pylori-induced acid hypersecretion, typically benign.
  • Gastric: pain worsened by food, more often linked to NSAIDs and must be biopsied to exclude malignancy.
• Every ulcer patient should be assessed for H. pylori and NSAID exposure.
• Bleeding posterior duodenal ulcers can erode the gastroduodenal artery and cause massive hemorrhage.
• Perforated ulcers classically present with sudden, severe epigastric pain, rigid abdomen, and free air under the diaphragm.
• Stopping PPIs too early or failing to eradicate H. pylori predisposes to recurrence.
• Stress ulcer prophylaxis is indicated in high-risk ICU patients but should not be indiscriminately used in all hospital admissions.^[3]
• Alarm features in dyspepsia warrant prompt endoscopic evaluation rather than empirical therapy alone.
• Gastric ulcers require follow-up EGD after treatment to document healing and exclude malignancy.
• In complicated PUD (perforation, peritonitis), prompt recognition and multidisciplinary management (surgical, endoscopic, and critical care) are essential to reduce morbidity and mortality.^{[5], [6]}

Summary

Peptic ulcer disease is a common and clinically important condition driven primarily by H. pylori infection, NSAID use, and impaired mucosal defenses. Modern management focuses on accurate diagnosis via endoscopy, appropriate testing and eradication of H. pylori, robust acid suppression with PPIs, and careful modification of ulcerogenic medications. Recognizing complications such as bleeding, perforation, and gastric outlet obstruction is vital for timely, often life-saving intervention. An understanding of the underlying pathophysiology helps integrate risk stratification, prophylaxis in high-risk settings, and long-term prevention strategies in both exam and clinical practice.^{[1], [2]}