L19 Gastrointestinal Disease

• Principles of Pathology
• Gastrointestinal Disease
• Dr Braeden Donaldson
• Lecture Objectives
• By the end of this lecture, you should be able to:

  1. Describe the aetiology and pathogenesis of reflux oesophagitis, and discuss how this can lead to Barrett oesophagus, oesophageal dysplasia, and oesophageal cancer

  2. Explain how chronic gastritis induced by H. pylori can lead to peptic ulcer disease, and discuss the pathogenesis and complications of peptic ulcer disease

  3. Compare and contrast the gross and histological features of Crohn disease and ulcerative colitis are two manifestations of inflammatory bowel disease
• Lecture Outline
• Lecture Outline


  • Oesophagus
  • Stomach
  • Large Intestine
  • Mouth-to-Anus
• Reflux oesophagitis


  Inflammation of the lower oesophagus caused by reflux of gastric contents, clinically presents as gastro-oesophageal reflux disease (GORD or GERD)

  
• Oesophageal epithelium


  • Stratified squamous mucosa for protection against abrasion and friction

  
• Gastric epithelium


  • Simple columnar mucosa for protection against gastric secretions

  
• Reflux of gastric secretions into the oesophagus causes a chemical injury, inducing inflammation of the oesophagus experienced as heart burn
• Aetiology of reflux oesophagitis

  • Relaxation of the lower oesophagus induced by vagal pathway in response to gastric distention
  • Abrupt changes in abdominal pressure (e.g. coughing, straining)
  • Alcohol, smoking, obesity, pregnancy, delayed gastric emptying, CNS depressants

  
• Reflux oesophagitis


  • Scattered intraepithelial eosinophils and mild basal zone expansion
  • Multiple erosions within the squamous oesophageal epithelium, and metaplastic mucosa (Barrett oesophagus)

  
• Barrett oesophagus


  Columnar (intestinal) metaplasia of the oesophagus, with stratified squamous mucosa replaced with simple columnar mucosa
• Barrett oesophagus can occur as a complication of chronic GORD
• Barrett oesophagus occurs in ~10% of patients with symptomatic GORD, and ~2% of the general population
• Barrett oesophagus is considered a precancerous or premalignant lesion, with mutations found in Barrett oesophagus also found in oesophageal adenocarcinoma

  
• Although Barrett oesophagus increases risk of oesophageal adenocarcinoma, not all patients with Barrett oesophagus will develop cancer

  
• Barrett oesophagus


  • Small islands of residual pale squamous mucosa
  • Low grade dysplasia
  • High grade dysplasia
• Majority of oesophageal cancers are either adenocarcinoma or squamous cell carcinoma (SCC), with SCC the most common worldwide

  
• Oesophageal adenocarcinoma is rising in developed countries, possibly due to increased incidence of obesity-related GORD and Barrett oesophagus
• Peptic ulcer disease (PUD)

  Ulceration of the mucosa lining the stomach (gastric ulcer), or small intestine (duodenal ulcer)

  
• Aetiology of peptic ulcer disease

  Imbalance between damaging and protective factors at mucosal surface

  
• Aetiological factors of peptic ulcer disease

  • H. pylori infection
  • Gastric hyperacidity
  • Oral NSAIDs
  • Alcohol/smoking
  • Duodenal-gastric reflux
• PUD most commonly occurs secondary to chronic gastritis induced by H. pylori, in combination with an increase in gastric acidity
• Symptoms of peptic ulcer disease

  • Epigastric pain, especially after meals, relieved by antacids
  • Nausea and vomiting
  • Bleeding and anaemia

  
• Most commonly affects the lesser curvature of the antrum in the stomach, or the first portion of the duodenum
• Helicobacter pylori


  Gram-negative spiral (helical) shaped curved rod bacteria which induces acute and chronic inflammation of the gastric mucosa (gastritis)
• Dr Barry J. Marshall won the Nobel prize for discovering the link between H. pylori and peptic ulcer disease, by experimenting on himself!
• Adaptations of H. pylori


  • Flagella – Used to burrow through the gastric mucus to reach the mucosal surface
  • Adhesins – Adheres to epithelial cell membranes
  • Urease – Produces ammonia from urea, neutralizing acid around the bacterium
• Most patients with gastric H. pylori have asymptomatic gastritis, but only 10-20% of patients with chronic gastritis develop peptic ulcer disease
• Treatment of H. pylori-induced peptic ulcer disease

  • Omeprazole (proton-pump inhibitor) to reduce gastric acidity
  • Clarithromycin and amoxicillin to treat the H. pylori infection
• Other than peptic ulcer disease, H. pylori induced gastritis increases the risk of gastric adenocarcinoma and lymphoma

  
• Gross peptic ulcer


  • H. Pylori-induced antral gastritis
  • Gastric ulcer with punched out straight edges, and base haemorrhage
  • Flattened rugae from remodelled fibrotic tissue

  
• Peptic ulcer histology


  • Muscularis, Necrotic Debris/Slough, Inflammation, Vascular Granulation Tissue, Fibrosis/Scar

  
• Healing of a peptic ulcer involves a combination of mucosal regeneration and fibrosis within the submucosa and deeper tissue layers

  
• Chronic bleeding occurs in 15-20% of patients, may present as anaemia and/or hematemesis (vomiting blood), and accounts for 25% of deaths
• Perforation of the gastric wall occurs in ~5% of patients, can penetrate into adjacent organs, and accounts for 2/3 of deaths
• Although there is an increased risk of gastric adenocarcinoma in patients with peptic ulcer disease, this is associated with the H. pylori-induced chronic gastritis rather than the actual peptic ulceration

  
• Inflammatory bowel disease (IBD)


  Chronic inflammatory condition affecting the bowel with two distinct presentations; ulcerative colitis or Crohn disease