3.1 Peptic Ulcer Disease & Upper GI Bleeding

Peptic Ulcer Disease & Upper GI Bleeding

Peptic ulcer disease (PUD) represents a mucosal break of $\ge 5\text{ mm}$ in diameter in the stomach or duodenum that penetrates through the muscularis mucosae. In UPSC Combined Medical Services (CMS) examinations, high-yield questions focus on distinguishing gastric from duodenal ulcers, understanding Helicobacter pylori diagnostic nuances, mastering the Forrest classification, and implementing acute resuscitation protocols for upper gastrointestinal bleeding (UGIB).

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Etiopathogenesis of Peptic Ulcer Disease

Gastric mucosal integrity depends on a balance between aggressive factors (acid, pepsin, H. pylori, NSAIDs, bile salts) and protective defenses (mucus-bicarbonate barrier, mucosal blood flow, epithelial renewal, prostaglandin $\text{E}_2$ and $\text{I}_2$).

1. Helicobacter pylori Infection

• Microbiology: Gram-negative, microaerophilic, flagellated curved bacillus residing in the non-acid-secreting gastric mucus layer.
• Pathogenic Virulence Factors:
  • Urease enzyme: Hydrolyzes urea into ammonia and $\text{CO}_2$, neutralizing gastric acid locally to create a protective microenvironment.
  • CagA (Cytotoxin-associated gene A): Translocated into epithelial cells via a Type IV secretion system, inducing interleukin-8 (IL-8) secretion, neutrophil infiltration, and oncogenic signaling.
  • VacA (Vacuolating cytotoxin A): Forms pores in epithelial cell membranes, inducing cell vacuolation and apoptosis.
• Pattern of Gastritis & Ulcer Disease:
  • Antral-predominant gastritis: Increases gastrin secretion (via destruction of somatostatin-producing D cells in the antrum), leading to hypergastrinemia, increased parietal cell mass, elevated basal acid output, and duodenal ulceration.
  • Pangastritis / Corpus-predominant gastritis: Causes parietal cell atrophy and hypochlorhydria, predisposing to gastric ulceration and gastric adenocarcinoma.

2. NSAID-Induced Ulceration

• Mechanism: Systemic inhibition of Cyclooxygenase-1 (COX-1) blocks the synthesis of mucosal protective prostaglandins ($\text{PGE}_2$ and $\text{PGI}_2$). This reduces gastric mucus and bicarbonate secretion, decreases mucosal blood flow, and impairs platelet aggregation.
• Risk Factors: Age $>65$ years, prior PUD/bleeding, high-dose NSAIDs, concomitant systemic corticosteroids, anticoagulants, or antiplatelet agents (e.g., aspirin, clopidogrel).

3. Zollinger-Ellison Syndrome (ZES / Gastrinoma)

• Severe PUD caused by a gastrin-secreting neuroendocrine tumor located in the Gastrinoma Triangle (Passaro Triangle): bounded by the junction of the cystic and common bile ducts superiorly, second/third portion of the duodenum inferiorly, and neck/body of the pancreas medially.
• Manifests with multiple refractory ulcers (often involving the distal duodenum or jejunum), severe diarrhea, and hypertrophic gastric folds.

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Clinical Distinctions: Duodenal vs. Gastric Ulcers

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Diagnostic Workup for H. pylori

Non-Invasive Diagnostic Tests

1. $\text{}^{13}\text{C}$ or $\text{}^{14}\text{C}$ Urea Breath Test (UBT): Gold-standard non-invasive test. Patient ingests labeled urea; bacterial urease cleaves it into labeled $\text{CO}_2$, measured in exhaled breath. Sensitivity and specificity $>95%$.
2. Stool Antigen Test (SAT): Enzyme immunoassay detecting H. pylori antigen in stool. Excellent for primary diagnosis and confirming post-treatment eradication (at least 4 weeks post-therapy).
3. Serology (IgG antibodies): Cannot distinguish active from past resolved infection (remains positive for years). Not recommended for confirming eradication.

Critical Clinical Rule for UPSC CMS: Proton pump inhibitors (PPIs) must be discontinued for at least 14 days, and antibiotics/bismuth compounds for at least 28 days prior to performing a UBT, Stool Antigen Test, or Rapid Urease Test. Failure to withhold these medications leads to false-negative results due to temporary suppression of bacterial load.

Invasive Tests (Endoscopy-Based)

1. Rapid Urease Test (RUT / CLOtest): Gastric antral biopsy placed in a urea-rich gel containing phenol red pH indicator. Bacterial urease converts urea to ammonia $\rightarrow$ raising pH $\rightarrow$ color change from yellow to magenta.
2. Histology: Modified Giemsa or Warthin-Starry silver stain permits direct visualization of bacilli and assessment of mucosal inflammation.

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Eradication Regimens for H. pylori

• Standard Bismuth Quadruple Therapy (First-line where clarithromycin resistance $>15%$):
  • PPI (Standard dose BID) + Bismuth subsalicylate (524 mg QID) + Metronidazole (500 mg TID-QID) + Tetracycline (500 mg QID) for 14 days.
• Concomitant Non-Bismuth Quadruple Therapy:
  • PPI (BID) + Amoxicillin (1000 mg BID) + Clarithromycin (500 mg BID) + Metronidazole (500 mg BID) for 14 days.

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Acute Upper Gastrointestinal Bleeding (UGIB)

UGIB is defined as intraluminal bleeding originating proximal to the ligament of Treitz (duodenojejunal flexure). PUD accounts for $\approx 50%$ of non-variceal UGIB cases.

Hemodynamic Resuscitation & Triage

• Airway & Access: Protect airway in altered sensorium; establish two large-bore peripheral IV lines (16G or 14G).
• Fluid Resuscitation: Crystalloids (Normal Saline or Ringer's Lactate) to maintain mean arterial pressure (MAP) $\ge 65\text{ mmHg}$.
• Restrictive Blood Transfusion Strategy: Transfuse Packed Red Blood Cells (PRBCs) at a hemoglobin threshold of $<7\text{ g/dL}$, targeting a post-transfusion Hb level of $7-9\text{ g/dL}$. (A higher threshold of $<8\text{ g/dL}$ applies to patients with active ischemic cardiovascular disease).
• Risk Stratification Scores:
  • Glasgow-Blatchford Score (GBS): Pre-endoscopic score utilizing blood urea, hemoglobin, systolic BP, pulse, melena, syncope, hepatic disease, and cardiac failure. A score of 0–1 identifies low-risk patients suitable for outpatient management without urgent EGD.
  • Rockall Score: Incorporates age, shock, comorbidities, endoscopic findings, and stigmata of recent hemorrhage to predict rebleeding risk and mortality.

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Endoscopic Stigmata: Forrest Classification

During esophagogastroduodenoscopy (EGD), ulcer bases are classified according to the Forrest criteria, which directly determine the need for endoscopic hemostatic therapy and predict rebleeding rates.

Endoscopic Hemostasis Techniques

• Dual therapy is superior to monotherapy: Submucosal Epinephrine injection (1:10,000 dilution; provides initial mechanical tamponade and vasoconstriction) PLUS a second mechanical or thermal modality (e.g., Hemoclips, Bipolar electrocautery, Argon Plasma Coagulation).
• Pharmacotherapy: High-dose IV PPI (e.g., Omeprazole 80 mg IV bolus followed by 8 mg/hour continuous IV infusion for 72 hours) stabilizes the fibrin clot by maintaining intragastric $\text{pH} > 6.0$.