Comprehensive Notes on Peptic Ulcer Disease (PUD), Gastritis, and Related Pathophysiology

Overview

• Peptic Ulcer Disease (PUD) involves disruption of the gastric or duodenal mucosal integrity due to damaging factors outpacing protective factors. Major causes: ext{H. pylori} infection and NSAID use; ischemia and Zollinger–Ellison syndrome are less common etiologies. PUD can present as gastric or duodenal ulcers with different location, pathophysiology, and clinical features.

Anatomy review (stomach) – key regions and layers

• Stomach cross-section anatomy: esophagus entry at the top; fundus (rounded top); body; pylorus (narrowing before the duodenum); antrum (lower stomach region); esophagogastric junction and pyloric sphincter control flow into the duodenum.
• Mucosal layers (from inside to outside): mucosa → submucosa → muscularis (smooth muscle layers) → serosa.
• Gastric mucosa surface features: gastric pits lined by mucus-secreting cells; goblet-like mucous cells form a protective barrier; rugae are the folds seen when the stomach is empty.
• Functional anatomy: parietal cells secrete hydrochloric acid (HCl) and intrinsic factor; G cells secrete gastrin (primarily in the antrum) to increase acid secretion; ECL cells release histamine to amplify acid secretion; chief cells secrete pepsinogen which converts to pepsin in the acidic environment.

Physiology of acid and mucosal protection

• Protective factors that maintain mucosal integrity:
  • Mucus layer forming a barrier between epithelium and acid.
  • Bicarbonate (HCO₃⁻) buffering in the mucosa.
  • Adequate blood flow to remove hydrogen and deliver nutrients for mucosal repair.
  • Epithelial cell integrity as a physical barrier.
  • Prostaglandins promote mucus and bicarbonate production and reduce acid secretion.
• Gastric acid biology: gastrin stimulates parietal cells; histamine from ECL cells further stimulates acid secretion; acetylcholine (ACh) also promotes acid secretion via neural input.
• Protective vs injurious factors balance is disrupted in PUD (erosion can progress to ulceration).

Major pathophysiology concepts for PUD

• H. pylori infection: gram-negative bacterium; releases toxins, triggers inflammation, and disrupts protective mechanisms; mechanism includes increased acid load in the antrum and altered gastric environment. Typical symptoms include burning sensation and dyspepsia; treated with antibiotics and acid suppression.
• NSAIDs: COX-1 inhibition → decreased prostaglandin synthesis → reduced mucosal protection (less mucus and bicarbonate) and increased acid exposure; direct mucosal toxicity also contributes.
• Ischemia: cellular hypoxia can contribute to mucosal injury; conditions include stress-related ulcers in ICU, curling ulcers after burns, and Cushing ulcers with brain injury.
• Other injurious/accelerating factors: alcohol, smoking, high caffeine/acidic beverages, and certain drugs can worsen mucosal injury.
• Zollinger–Ellison syndrome: gastrin-secreting tumor → markedly increased acid production; considered in refractory acid hypersecretion cases.
• Erosion vs ulcer: erosion is superficial; ulceration penetrates into deeper layers (mucosa, submucosa, possibly muscularis).

Clinical presentation and bleeding signs

• Common symptoms include epigastric pain, dyspepsia, nausea/vomiting, and sometimes GI bleeding.
• Bleeding manifestations: occult or overt GI bleeding; melena (black, tarry stools) indicates digested blood; hematemesis (vomiting blood); coffee-ground emesis indicates partially digested blood.
• Early sign of GI bleeding (circulation-focused nursing pearl): tachycardia is often the earliest sign of hemorrhage; hypotension may follow as bleeding progresses.
• Pain patterns help differentiate ulcers:
  • Duodenal ulcer: pain occurs 1.5–3 hours after meals or on an empty stomach and is relieved by food.
  • Gastric ulcer: pain 0.5–1 hour after meals and may worsen with meals; often worsened at night.
• Nutritional status: duodenal ulcers patients are often well-nourished because eating relieves pain; gastric ulcers may cause anorexia and potential malnutrition or weight loss.
• Recurrence: duodenal ulcers have a relatively high recurrence but different patterns from gastric ulcers (see below).

Duodenal vs Gastric ulcers – key comparison

• Location:
  • Duodenal: proximal duodenum (top of the duodenum).
  • Gastric: antrum of the stomach.
• Acidity and pH effects:
  • Duodenal ulcers: high gastric acid secretion; lower pH (acidic environment) promotes ulcer formation.
  • Gastric ulcers: normal to low acid secretion; pH may be less acidic in some cases.
• Incidence by age group:
  • Duodenal ulcers: 20-50 years.
  • Gastric ulcers: 50-70 years.
• Clinical manifestations: duodenal ulcers—pain after meals or during fasting relieved by eating; gastric ulcers—pain after meals or at night, worsened by meals.
• Recurrence rate: duodenal ulcers have a tendency to recur, with 60 ext{ extbf{%}} within one year and up to 90 ext{ extbf{%}} within two years.
• Blood test/bleeding pattern:
  • Duodenal: more commonly occult blood in stool (melena).
  • Gastric: more commonly hematemesis or coffee-ground emesis.
• Associated gastritis and nutritional status: less associated with gastritis in some gastric ulcers; duodenal ulcers often have preserved nutrition; gastric ulcers can be linked with gastritis and potential atrophic changes.
• Malignancy potential: duodenal ulcers have lower malignant potential; gastric ulcers have a malignancy risk of less than 10 ext{ extbf{%}}.

Diagnostic approach and labs/tests

• History and physical: dyspepsia, epigastric pain, GI bleeding signs; assess for alarm features and age thresholds.
• Laboratory tests:
  • CBC (complete blood count) to assess anemia and WBC if infection/inflammation suspected.
  • CMP (electrolytes, glucose, liver enzymes like AST/ALT, bilirubin, albumin) to assess nutrition and organ function. Albumin is a marker for nutritional status.
  • Other potential labs as indicated (e.g., coagulation studies, stool tests).
• H. pylori testing:
  • Urea breath test (breath test) – historically explained with a pudding ingestion protocol in teaching; detects active infection via urease activity.
  • Stool antigen test – described as the best and most accurate noninvasive test for active infection.
  • Serology is less preferred due to inability to distinguish past vs current infection.
• Endoscopy and biopsy: upper endoscopy with biopsy to assess for ulcers, infection, and malignancy; endoscopy is used for direct visualization and to obtain specimens.
• Additional imaging:
  • Barium swallow/esophagogram to visualize anatomy and functional transit when endoscopy is not feasible.
  • Upper GI series can help identify ulcers but endoscopy with biopsy remains the gold standard for diagnosis.
• pH monitoring (24-hour) and GERD considerations: used in differential diagnosis when reflux disease is suspected rather than classic PUD.

Pathway to management — initial approach

• First-line therapy for H. pylori-associated PUD (7–14 days):
  • Triple therapy (PPI + amoxicillin + clarithromycin) for 7-14 ext{ days} (adjust if penicillin allergy with alternative antibiotics such as metronidazole).
• Alternative first-line therapy (quadruple therapy):
  • PPI + bismuth subsalicylate + tetracycline + metronidazole for 10-14 ext{ days}.
• Sequential therapy (alternative approach):
  • Phase 1: PPI + amoxicillin for about 5 ext{ days};
  • Phase 2: PPI + clarithromycin + metronidazole for about 5 ext{ days}.
• Levofloxacin-based therapy (for penicillin-allergic or resistant cases):
  • PPI + amoxicillin + levofloxacin for 10-14 ext{ days}.
• Non–eradication management: continue PPI therapy to promote mucosal healing; assess and treat complications as they arise.
• Non-pharmacologic measures active in all cases:
  • Avoid NSAIDs (unless medically necessary and alternatives used with gastroprotection);
  • Alcohol abstinence; avoid smoking; limit caffeine and highly acidic beverages; avoid large meals before bed; consider smaller, more frequent meals; maintain hydration and balanced nutrition.
• Therapies for symptom control and healing:
  • Proton pump inhibitors (PPI) such as omeprazole to suppress acid production.
  • H2 receptor antagonists (e.g., ranitidine) as alternative or adjuncts.

Special clinical notes and patient education

• GERD and its relation to PUD: some overlap in mucosal injury mechanisms and diagnostic approaches (pH monitoring, endoscopy). In children, GERD can manifest as Sandifer syndrome (posturing with tilted head and arched back in infants).
• When to suspect malignancy or complex etiologies: Barrett’s esophagus risk and other conditions; more common in atypical presentations or non-healing ulcers; ensure biopsy when endoscopy is performed.
• Important nonpharmacologic patient education points:
  • Keep a food diary to identify trigger foods; eat smaller, more frequent meals; avoid meals near bedtime; rest upright after eating; manage stress; engage in regular exercise (e.g., yoga or meditation).
  • Smoking cessation and limiting alcohol intake; avoid NSAIDs or use gastroprotective strategies if NSAIDs are unavoidable.
  • For acetaminophen (Tylenol) users: monitor total daily dose due to hepatotoxicity risk, especially with alcohol use.
  • Educate on recognizing red-flag symptoms (progressive weakness, syncope, severe abdominal pain, vomiting blood, black stools) and seek urgent care if they occur.

Complications and emergency considerations

• Hemorrhage: most common ulcer complication; managed with endoscopic hemostasis if possible, and PPI therapy; tachycardia is an early sign of hemorrhage prior to hypotension.
• Perforation: an emergency with sudden severe abdominal pain and signs of peritonitis; requires urgent surgical evaluation.
• Gastric outlet obstruction: presents with early satiety, nausea, vomiting, bloating; may require imaging and endoscopy for evaluation.
• Ulcer-related cancer risk: gastric ulcers carry a small risk of malignancy; duodenal ulcers have a lower malignant potential.

Practical clinical pearls

• When evaluating suspected PUD, differentiate between gastric and duodenal ulcers using: location, pain pattern relative to meals, age, and bleeding presentation.
• The earliest systemic sign of GI bleeding is tachycardia, underscoring the need for rapid assessment and monitoring.
• H. pylori testing strategy: prefer noninvasive tests (urea breath test or stool antigen) to confirm active infection; endoscopy with biopsy if red flags or suspicion of complications.
• The breath test involves ingestion of a marker (e.g., labeled urea) and measuring exhaled CO₂; H. pylori activity produces detectable changes. Stool antigen testing is noted as highly accurate for active infection.
• If NSAID-induced ulcers are suspected, reassess pain management strategies and consider gastroprotective regimens (PPI or misoprostol) if NSAIDs must be used.
• Nutritional status monitoring: albumin level is a useful indicator of nutritional reserve; significant unintentional weight loss prompts assessment of nutrition and possible complications.

Quick reference: summary points to memorize

• PUD = disruption of gastric/duodenal mucosa due to injurious factors exceeding protective factors. Major causes: ext{H. pylori}, NSAIDs.
• Gastric ulcers vs duodenal ulcers: location, acid secretion, pH, age distribution, pain timing, bleeding patterns, recurrence, and cancer risk differ.
• H. pylori testing: stool antigen is highly accurate; urea breath test is commonly used; endoscopy with biopsy confirms ulcers and evaluates for cancer.
• First-line eradication regimens (typical framework):
  • Triple therapy: PPI + amoxicillin + clarithromycin for 7-14 ext{ days}; alternatives if penicillin allergy.
  • Quadruple therapy: PPI + bismuth + tetracycline + metronidazole for 10-14 ext{ days}.
  • Sequential therapy: phase-wise PPI + amoxicillin, then PPI + clarithromycin/metronidazole.
  • Levofloxacin-based therapy for selected cases: PPI + amoxicillin + levofloxacin for 10-14 ext{ days}.
• Early detection of complications (tachycardia, abdominal pain, vomiting blood, dark stools) guides urgent escalation of care.
• GERD/peptic disease care emphasizes lifestyle modification, appropriate pharmacotherapy, and selective use of procedures (endoscopy) based on symptoms and risk factors.

Connections to foundational principles

• The balance of protective versus injurious factors in mucosal biology underpins all ulcer pathology: acid secretion, mucus/bicarbonate, mucosal blood flow, and epithelial barrier integrity.
• Hormonal and neural regulation of acid production (gastrin, histamine, ACh) explains how dysregulation leads to ulcers and how acid-suppressive therapies promote healing.
• Understanding the natural history and recurrence risk informs both pharmacologic therapy and patient counseling on lifestyle changes.
• Diagnostic strategies integrate noninvasive testing, imaging, endoscopy, and histology to differentiate infection from NSAID damage and to exclude malignancy.