4.1 Upper & Lower GI Disorders & Inflammatory Bowel Disease

Upper & Lower GI Disorders & Inflammatory Bowel Disease

Esophageal & Upper Gastrointestinal Disorders

Esophageal pathology spans motor disorders and mucosal injury. Precise clinical evaluation requires combining endoscopy, barium swallow, and high-resolution manometry (HRM).

Esophageal Motility Disorders

Esophageal motility disorders present primarily with dysphagia, chest pain, and regurgitation. The Chicago Classification version 4.0 categorizes these based on high-resolution esophageal manometry (HRM):

• Achalasia: Characterized by incomplete relaxation of the lower esophageal sphincter (LES) and aperistalsis of the esophageal body. It results from degeneration of the myenteric plexus (Auerbach's plexus) post-ganglionic inhibitory neurons (which produce nitric oxide and vasoactive intestinal peptide).
  • Type I (Classic): 100% failed peristalsis with elevated mean Integrated Relaxation Pressure (IRP >15 mmHg).
  • Type II (with Esophageal Compression): Elevated IRP with pan-esophageal pressurization in ≥20% of swallows.
  • Type III (Spastic): Elevated IRP with spastic/premature contractions (Distal Latency <4.5 seconds) in ≥20% of swallows.
  • Diagnostic Evaluation: Barium swallow shows a dilated esophagus with smooth, symmetric tapering at the lower esophageal sphincter ("bird's-beak" sign). Endoscopy is essential to rule out pseudo-achalasia (e.g., adenocarcinoma of the gastroesophageal junction).
  • Management: Pneumatic balloon dilation or Peroral Endoscopic Myotomy (POEM). Surgical Heller myotomy with partial fundoplication (Dor or Toupet) is an alternative. Medical options (nifedipine, sublingual nitrates, botulinum toxin injection into the LES) are reserved for poor surgical candidates.
• Distal Esophageal Spasm (DES): Presents with chest pain and dysphagia. HRM shows normal IRP with premature contractions (DL <4.5 s) in ≥20% of swallows. Barium swallow shows a "corkscrew esophagus". Treated with calcium channel blockers, nitrates, or low-dose tricyclic antidepressants.
• Hypercontractile (Jackhammer) Esophagus: Defined by a Distal Contractile Integral (DCI) >8000 mmHg·s·cm in ≥20% of swallows with normal IRP.

Gastroesophageal Reflux Disease (GERD) & Barrett's Esophagus

GERD results from transient lower esophageal sphincter relaxations (TLESRs). Warning symptoms ("red flags") warranting urgent upper GI endoscopy within 2 weeks include progressive dysphagia, unexplained weight loss >5%, persistent vomiting, or anemia.

• Barrett's Esophagus: Metaplasia of the normal stratified squamous epithelium of the lower esophagus into specialized columnar epithelium with goblet cells, driven by chronic acid and bile exposure. It is a pre-malignant condition for esophageal adenocarcinoma (risk ~0.2–0.5% per year).
• Prague C & M Classification: Standardized endoscopic grading:
  • C value: Circumferential extent (in cm).
  • M value: Maximum extent including tongues of metaplasia (in cm).
• Surveillance Guidelines (BSG):
  • Short-segment (<3 cm): Endoscopy every 2–5 years.
  • Long-segment (≥3 cm): Endoscopy every 2–3 years.
  • Low-grade dysplasia: Radiofrequency ablation (RFA) or repeat endoscopy at 6 months.
  • High-grade dysplasia or intramucosal carcinoma: Endoscopic mucosal resection (EMR) for visible lesions combined with RFA.

Eosinophilic Esophagitis (EoE)

EoE is an immune-mediated chronic inflammatory disorder triggered by food allergens. Clinical features include dysphagia to solids and recurrent food bolus impaction in young adults with an atopic history (asthma, eczema, allergic rhinitis).

• Endoscopic Findings: Trachealization (concentric rings), linear furrows, feline esophagus, and mucosal fragility ("crepe-paper" mucosa).
• Diagnostic Criteria: Mucosal biopsies demonstrating ≥15 eosinophils per high-power field (HPF) in the esophagus after ruling out non-EoE causes of esophageal eosinophilia.
• Management: Topical swallowed corticosteroids (fluticasone propionate or oral viscous budesonide 1 mg BD), proton pump inhibitors (PPIs e.g., omeprazole 20–40 mg BD), or six-food elimination diet (dairy, wheat, egg, soy, nuts, seafood). Biologic therapy with dupilumab (anti-IL-4/IL-13) is approved for refractory cases.

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Peptic Ulcer Disease & Helicobacter pylori

Peptic Ulcer Disease (PUD) primarily arises from Helicobacter pylori infection or Non-Steroidal Anti-Inflammatory Drug (NSAID) use.

Helicobacter pylori Infection

H. pylori is a gram-negative, microaerophilic spiral bacterium residing in the gastric mucosa. It produces urease, converting urea to ammonia and carbon dioxide, buffering local gastric acid.

Eradication Regimens (BSG Guidelines)

Due to rising clarithromycin resistance (>15% in many European regions), first-line eradication strategies depend on local resistance profiles:

1. First-Line Triple Therapy (Low Clarithromycin Resistance Areas): PPI (e.g., Omeprazole 20 mg BD) + Amoxicillin 1 g BD + Clarithromycin 500 mg BD for 14 days.
2. Bismuth Quadruple Therapy (High Clarithromycin Resistance Areas or Previous Macrolide Exposure): PPI BD + Bismuth subsalicylate 524 mg QDS + Metronidazole 400 mg TDS + Tetracycline 500 mg QDS for 14 days.
3. Post-Eradication Testing: Mandatory in patients with gastric ulcer, MALT lymphoma, persistent dyspepsia, or post-resection for gastric cancer. Must be performed at least 4 weeks after completing antibiotics and 2 weeks off PPI therapy using UBT or Stool Antigen Test.

Zollinger-Ellison Syndrome (ZES)

ZES is caused by a gastrin-secreting neuroendocrine tumor (gastrinoma), located in 80% of cases within the "gastrinoma triangle" (bounded by the cystic/common bile duct junction, second/third portion of the duodenum, and neck/body junction of the pancreas). Approximately 25% occur as part of Multiple Endocrine Neoplasia Type 1 (MEN1).

• Clinical Presentation: Multiple refractory peptic ulcers, atypical ulcers (duodenal bulb/jejunum), severe GERD, and chronic diarrhea (due to acid inactivation of pancreatic lipase).
• Diagnosis: Fasting serum gastrin level >1000 pg/mL with gastric pH <2.0. If gastrin is elevated (100–1000 pg/mL) but inconclusive, a secretin stimulation test is performed (IV secretin 2 U/kg causes a paradoxical rise in gastrin >200 pg/mL in ZES).

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Inflammatory Bowel Disease: Crohn's Disease vs. Ulcerative Colitis

Inflammatory Bowel Disease (IBD) encompasses Crohn's Disease (CD) and Ulcerative Colitis (UC), complex idiopathic chronic inflammatory disorders of the gastrointestinal tract.

Comparative Features of CD vs. UC

Acute Severe Ulcerative Colitis (ASUC)

ASUC is a medical emergency requiring inpatient admission. It is defined using the Truelove and Witts Criteria.

Truelove and Witts Criteria for Severe UC

Requires ≥6 bloody stools per day PLUS at least one of the following signs of systemic toxicity:

1. Fever: Temperature >37.8°C (100.0°F)
2. Tachycardia: Heart rate >90 beats per minute
3. Anemia: Hemoglobin <105 g/L (10.5 g/dL)
4. Inflammatory Markers: ESR >30 mm/hr or CRP >30 mg/L

Clinical Management Pathway

• Day 0 to 3: Admission, stool microbiology (C. difficile PCR and parasite culture), IV Hydrocortisone 100 mg QDS (or Methylprednisolone 60 mg OD), subcutaneous low-molecular-weight heparin for VTE prophylaxis, and joint surgical-medical review.
• Day 3 Assessment (Travis / Oxford Criteria): Stool frequency >8/day OR stool frequency 3–8/day combined with CRP >45 mg/L predicts an 85% colectomy rate.
• Rescue Medical Therapy: Initiate IV Infliximab 5 mg/kg (or IV Ciclosporin 2 mg/kg/day) if no response by day 3.
• Day 7 Evaluation: If rescue therapy fails, proceed to urgent subtotal colectomy with end ileostomy.

Medical Maintenance Therapy in IBD

• 5-Aminosalicylates (5-ASA / Mesalazine): First-line for mild-to-moderate UC (oral + topical enema/suppository). Minimal role in Crohn's disease.
• Thiopurines (Azathioprine 2.0–2.5 mg/kg/day / Mercaptopurine 1.0–1.5 mg/kg/day): Steroid-sparing maintenance. Thiopurine S-methyltransferase (TPMT) activity or NUDT15 genotype must be tested prior to initiation to prevent life-threatening bone marrow aplasia in deficient individuals.
• Biologics & Targeted Small Molecules:
  • Anti-TNF Agents: Infliximab, Adalimumab, Golimumab. Pre-screening required for latent tuberculosis (IGRA/Chest X-ray) and Hepatitis B/C.
  • Anti-Integrin (α4β7): Vedolizumab (gut-selective inhibition of leukocyte trafficking).
  • Anti-IL-12/IL-23: Ustekinumab (p40 subunit inhibitor) and Risankizumab/Mirikizumab (p19 subunit inhibitors).
  • JAK Inhibitors: Tofacitinib, Upadacitinib, Filgotinib (oral small molecules for UC; evaluate cardiovascular risk, VTE history, and zoster vaccination status).
  • Sphingosine-1-Phosphate (S1P) Receptor Modulators: Ozanimod, Etrasimod.

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Microscopic Colitis & Lower GI Pathologies

Microscopic Colitis

Microscopic colitis causes chronic, watery, non-bloody diarrhea, typically in middle-aged or elderly women. Colonoscopy reveals macroscopically normal or near-normal mucosa; diagnosis rests entirely on histopathology from random mucosal biopsies.

• Triggers: NSAIDs, Proton Pump Inhibitors (lansoprazole, omeprazole), SSRIs, and statins.
• Subtypes:
  1. Collagenous Colitis: Subepithelial collagen band >10 µm in thickness (normal <7 µm) beneath the luminal epithelium.
  2. Lymphocytic Colitis: Intraepithelial lymphocytes (IELs) ≥20 per 100 enterocytes, accompanied by mucosal inflammation without collagen thickening.
• Treatment: First-line targeted therapy is oral Budesonide 9 mg daily for 8 weeks, which induces clinical and histological remission in >80% of patients. Symptomatic antidiarrheals (loperamide) are adjuncts.