4. GERD and PUD

 

 

1. Gastroesophageal Reflux Disease (GERD)

Pathophysiology

  • GERD occurs due to dysfunction of the lower esophageal sphincter (LES), resulting in retrograde flow of stomach contents into the esophagus.
  • Key contributing factors:
    • Transient LES relaxations.
    • Hiatal hernia.
    • Impaired esophageal motility.
    • Delayed gastric emptying.

Clinical Features

  • Typical Symptoms:
    • Heartburn (burning retrosternal discomfort).
    • Acid regurgitation.
  • Atypical/Extra-esophageal Symptoms:
    • Chronic cough, asthma, laryngitis, non-cardiac chest pain.
  • Alarm Symptoms:
    • Dysphagia, odynophagia, weight loss, GI bleeding (indicative of malignancy or complications).
    • Note: Reflux itself does not typically cause odynophagia—investigate for infections such as HSV, CMV, or candidiasis.

Diagnostic Approach

  • Clinical Diagnosis: Typical symptoms with response to PPI trial.
  • Endoscopy:
    • Indicated in patients with alarm symptoms or PPI-refractory GERD.
    • Assess for erosive esophagitis, Barrett’s esophagus.
    • Los Angeles (LA) Classification for Erosive Esophagitis:

Grade

Endoscopic Findings

A

Mucosal break ≤ 5 mm that does not extend between folds

B

Mucosal break > 5 mm but does not extend between folds

C

Mucosal break continuous between folds, < 75% of circumference

D

Mucosal break involving ≥ 75% of the esophageal circumference
    • Surveillance Recommendation:
      • Recommended only for patients with grades C or D esophagitis after 6–8 weeks of PPI therapy.
      • Routine surveillance not recommended for LA grades A or B.
  • Esophageal pH Monitoring (± Impedance):
    • Confirms GERD in endoscopy-negative cases.
    • Useful in atypical symptoms or prior to surgical interventions.
    • Demeester Score Components:
      • Supine reflux episodes.
      • Upright reflux episodes.
      • Total reflux duration.
      • Number of reflux episodes.
      • Episodes > 5 minutes.
      • Longest reflux episode.
    • Interpretation: A Demeester score > 14.72 indicates pathological acid reflux.
  • High-Resolution Manometry (HRM):

Management

  • Lifestyle Modifications:
    • Weight loss, head-of-bed elevation, avoidance of late meals, trigger foods.
  • Pharmacological Treatment:
    • First-line: Proton pump inhibitors (PPIs) (e.g., omeprazole) for 8 weeks.
    • Second-line: H2 receptor antagonists or PPI dose adjustment.
  • Surgical Intervention:
    • NICE Recommendations: Consider laparoscopic fundoplication for patients with:
      • Confirmed acid reflux and adequate symptom control with PPIs but preference for surgical management.
      • Confirmed acid reflux with PPI-responsive symptoms but intolerance to long-term acid suppression therapy.

2. Peptic Ulcer Disease (PUD)

Pathophysiology

  • Definition: Mucosal defect in the stomach or duodenum due to an imbalance between protective factors (mucus, bicarbonate, prostaglandins) and harmful factors (acid, pepsin).
  • Aetiology:
    • Helicobacter pylori infection.
    • NSAID use (inhibits prostaglandin synthesis).
    • Zollinger-Ellison syndrome (gastrin-secreting tumor).

Clinical Features

  • Gastric Ulcer:
    • Epigastric pain worsens with food.
    • Associated with nausea, early satiety.
  • Duodenal Ulcer:
    • Epigastric pain relieved by food or antacids.
    • Pain recurs 2-3 hours postprandially or at night.
  • Complications:
    • GI bleeding (melena, hematemesis).
    • Perforation (acute severe abdominal pain).
    • Gastric outlet obstruction.

Diagnostic Approach

  • Endoscopy:
    • Gold standard for visualizing ulcers.
    • Biopsy indicated to rule out malignancy (especially for gastric ulcers).
  • H. pylori Testing:
    • Culture of Gastric Biopsy: Sensitivity ~72%.
    • Rapid Urease Test: 80-95% sensitivity, 95-100% specificity.
    • Histology: 80-90% sensitivity, 95% specificity.
    • Urea Breath Test: 95% sensitivity, 98-100% specificity.
    • Serology (IgG antibodies): Indicates past infection—potentially useful when PPIs cannot be stopped.
    • Note: Gastric biopsy results can be false negative following PPI treatment.
    • Post-treatment eradication confirmation: Urea breath test or stool antigen test (both indicate active infection).

Impact of Eradication Therapy

  • Duodenal Ulcers:
    • Slightly increases healing (5.4% additional benefit over acid suppression alone).
    • Significantly decreases recurrence (52% more patients ulcer-free at 12 months).
  • Gastric Ulcers:
    • No significant effect on healing.
    • Reduces recurrence (32% more patients ulcer-free at 12 months).
  • NSAID-induced Ulcers:
    • No significant effect on healing when NSAIDs are continued.
    • Continued NSAID use markedly reduces the benefit of eradication therapy on recurrence.

Zollinger-Ellison Syndrome (Gastrinoma)

  • Presentation: Multiple duodenal ulcers, refractory to PPI treatment, and possible diarrhea.
  • Diagnostic Steps:
    1. Endoscopy (OGD): Identifies multiple or PPI-resistant duodenal ulcers, possibly enlarged gastric folds.
    2. Low Gastric pH (<2) despite PPI use.
    3. Fasting Gastrin > 1000 pg/mL (10x upper limit of normal).
    4. If gastrin < 1000 pg/mL: Perform a Secretin Stimulation Test (off PPI if possible, except in severe cases).
    5. Imaging for Localization:
      • CT, MRI, or radio-labeled somatostatin scintigraphy.
      • Endoscopic ultrasound (EUS) for detecting small tumors.
    6. Chromogranin A: Less sensitive than gastrin and can be falsely elevated with PPI use.
  • Differential Diagnosis: Antral G-cell hyperplasia (poor response to secretin test, no tumor on imaging).
  • Association: Look for MEN1 syndrome (parathyroid, pancreatic, and pituitary tumors).
  • Treatment:
    1. PPI Therapy: High-dose to control acid secretion.
    2. Octreotide: Consider if PPI therapy is inadequate.
    3. Localized Tumor: Surgical resection (especially in MEN1 with multifocal tumors).
    4. Metastatic Disease: Liver resection or embolization; consider octreotide.

Management

  • Lifestyle Changes:
    • Avoid NSAIDs, smoking, alcohol, and stress.
  • Pharmacological Therapy:
    • First-Line H. pylori Eradication (7-Day BID Therapy):

Scenario

Regimen

First-Line

PPI + Amoxicillin + Clarithromycin

Alternative First-Line

PPI + Amoxicillin + Metronidazole

Penicillin Allergy

PPI + Clarithromycin + Metronidazole

Pen Allergy, Prior Clari

PPI + Bismuth + Metronidazole + Tetracycline
    • Second-Line Therapy:
      • No penicillin allergy: PPI + amoxicillin + clarithromycin/metronidazole (whichever was not used first-line).
      • Previous exposure to clarithromycin and metronidazole: PPI + tetracycline (or levofloxacin if tetracycline cannot be used).
      • Penicillin Allergy:
        • No prior quinolone exposure: PPI + metronidazole + levofloxacin.
        • Prior quinolone exposure: PPI + bismuth + metronidazole + tetracycline.
  • NSAID-induced ulcers:
    • Discontinue NSAIDs and initiate PPIs for 8-12 weeks.
    • Consider prophylaxis with PPIs for high-risk NSAID users.
  • Surgical Intervention:
    • Reserved for complications such as perforation or refractory bleeding.

References

  1. NICE CG184 – GERD and Dyspepsia Guidelines.
  2. Lyon Consensus. Modern Diagnosis of GERD Accessed online.
  3. ESGE Guidelines for PUD Management ESGE 2019.

 

Images:


Figure 1: Reflux oesophagitis.