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Pathogenesis of Diseases of the Oesophagus

Pathogenesis of Diseases of the Oesophagus. Dr Paul L. Crotty Departement of Pathology AMNCH, Tallaght October 2008. Classification of Disease by Aetiology. Congenital Acquired Infection Physical/Trauma Chemical/Toxic Circulatory disturbances Immunological disturbance

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Pathogenesis of Diseases of the Oesophagus

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  1. Pathogenesis of Diseases of the Oesophagus Dr Paul L. Crotty Departement of Pathology AMNCH, Tallaght October 2008

  2. Classification of Disease by Aetiology • Congenital • Acquired • Infection • Physical/Trauma • Chemical/Toxic • Circulatory disturbances • Immunological disturbance • Degenerative disorders • Iatrogenic • Idiopathic • Multifactorial • Various: radiation, nutritional deficiency, psychosomatic • Pre-neoplastic/ Neoplastic

  3. Classification of Disease by Aetiology • Congenital • Acquired • Infection Disease A • Physical/Trauma • Chemical/Toxic • Circulatory disturbances • Immunological disturbance Pathogenetic process • Degenerative disorders • Iatrogenic • Idiopathic Disease B • Multifactorial • Various: radiation, nutritional deficiency, psychosomatic • Pre-neoplastic/ Neoplastic

  4. Oesophagus: classification by aetiology • Congenital: atresia, stenosis, fistulas, webs • Acquired • Infection:fungal infection, viral infection, Chagas’ disease • Physical/Trauma: lacerations • Chemical/Toxic: gastro-oesophageal reflux disease (GORD) • Circulatory disturbances: oeophageal varices • Immunological disturbance:eosinophilic oesophagitis • Degenerative disorders • Iatrogenic:pill oesophagitis • Idiopathic:achalasia • Multifactorial • Various: radiation, nutritional deficiency, psychosomatic • Pre-neoplastic/ Neoplastic:Barrett’s oesophagus -> adenocarcinoma squamous cell carcinoma

  5. Normal Oesophagus

  6. Normal Oesophagus • Functions • Tube to conduct food into stomach • Prevent reflux of gastric contents • Prevent passive diffusion of food, bacteria • To achieve these functions • peristalsis, coordinated with swallowing • sphincter at lower oesophagus: tonic, relax for swallow • lined by stratified squamous mucosa

  7. Manometry: normal oesophagus

  8. Gastro-Oesophageal Reflux Disease (GORD) • Abnormal retrograde movement of stomach contents to oesophagus • Hydrochloric acid, pepsin • Very common • ~ 1 in 12 people heartburn daily • ~ 1 in 6 heartburn weekly • Oesophagitis in ~5%

  9. Gastro-Oesophageal Reflux Disease (GORD) • Normally, reflux prevented by: • Lower oesophageal sphincter • Anatomic structure (acute angle with stomach, crus of diaphragm) • Oesophageal peristaltic clearance • Swallowed saliva • Gravity

  10. Gastro-Oesophageal Reflux Disease (GORD) • Reflux more likely to occur when: • Decreased tone of sphincter • Sliding hiatal hernia • Decreased oesophageal clearance • Decreased saliva production • When lying down

  11. Gastro-Oesophageal Reflux Disease (GORD) • Hydrochloric acid and pepsin • -> H+ ions diffuse into cells • -> acidification of mucosa • -> inflammation, necrosis

  12. Gastro-Oesophageal Reflux Disease (GORD) • Clinical: symptoms of heartburn • Endoscopic: red/congested mucosa • Manometric: decreased sphincter pressure • pH: number, duration of dips: pH<4 • Pathological: microscopic evidence of oesophagitis

  13. Definition of GORD? Clinical Endoscopic Microscopic

  14. Endoscopic appearance Normal Inflamed

  15. Hiatal Hernia

  16. Hiatal hernia • Sliding type in 95% (5% para-oesophageal) • Common anatomic abnormality • Up to 20% of adults • Associated with GORD • Loss of acute angle with stomach • Right crus of diaphragm contributes to functional level of sphincter pressure

  17. Complications of GORD • Ulceration • Haemorrhage • Perforation • Fibrotic stricture • Aspiration • Barrett’s oesophagus • risk of dysplasia and malignancy

  18. Complications of GORD Ulceration Stricture

  19. Barrett’s oesophagus • As a long term complication of reflux, the normal squamous mucosa of the oesophagus becomes replaced by glandular mucosa: ?stem cell differentiation • Clinical importance is when it is replaced by intestinal-type cells, esp goblet cells: intestinal metaplasia • Risk of progression to dysplasia and adenocarcinoma

  20. Barrett’s oesophagus • Long segment (>3cm) • Short segment (<3cm) • Risk of adenocarcinoma in long segment disease is ~30-40X the general population risk • Risk is proportional to length of disease • Surveillance programmes

  21. Fungal infection • Usually Candida • Normal oral flora • Colonises, proliferates in oesophagus • Debilitated patients • Immunosuppressed (steroids, HIV, other) • Broad spectrum antibiotics • Inflammation, erosions, ulceration

  22. Candida oesophagitis

  23. Viral infection • Usually Herpes simplex virus (HSV) • Usually re-activation • Virus infects squamous cells -> cell death • Vesicles, erosions, ulceration • Clinical setting • Debilitated patients • Immunosuppressed (steroids, HIV, other) • Can occur in immunocompetent patients

  24. Herpes simplex oesophagitis

  25. Oesophagus: classification by aetiology • Congenital: atresia, stenosis, fistulas, webs • Acquired • Infection:fungal infection, viral infection, Chagas’ disease • Physical/Trauma: lacerations • Chemical/Toxic: gastro-oesophageal reflux disease (GORD) • Circulatory disturbances: oeophageal varices • Immunological disturbance:eosinophilic oesophagitis • Degenerative disorders • Iatrogenic:pill oesophagitis • Idiopathic:achalasia • Multifactorial • Various: radiation, nutritional deficiency, psychosomatic • Pre-neoplastic/ Neoplastic:Barrett’s oesophagus -> adenocarcinoma squamous cell carcinoma

  26. Achalasia • “failure to relax” • idiopathic disorder of muscle of oesophagus • loss of peristalsis • increased resting tone of lower sphincter • loss of normal relaxation with swallowing • muscular spasm

  27. Manometry in achalasia Normal Achalasia

  28. Achalasia • Dysphagia, pain • Food bolus stuck • Aspiration • Mega-oesophagus • Risk of squamous cell carcinoma

  29. Chagas’s disease • Infection with Trypanosoma cruzi • Mexico, Central and South America • Destruction of nerve plexuses in oesophagus • Also rest of GI tract, ureter • Functional impairment similar to achalasia

  30. Mega-oesophagus

  31. Oesophagus: classification by aetiology • Congenital: atresia, stenosis, fistulas, webs • Acquired • Infection:fungal infection, viral infection, Chagas’ disease • Physical/Trauma: lacerations • Chemical/Toxic: gastro-oesophageal reflux disease (GORD) • Circulatory disturbances: oeophageal varices • Immunological disturbance:eosinophilic oesophagitis • Degenerative disorders • Iatrogenic:pill oesophagitis • Idiopathic:achalasia • Multifactorial • Various: radiation, nutritional deficiency, psychosomatic • Pre-neoplastic/ Neoplastic:Barrett’s oesophagus -> adenocarcinoma squamous cell carcinoma

  32. Pill oesophagitis • Chemical injury • Pill temporarily held up in oesophagus • Contact time • Chemical nature of medication • Size, solubility, coating • Common with KCl, NSAIDs

  33. Oesophagus: classification by aetiology • Congenital: atresia, stenosis, fistulas, webs • Acquired • Infection:fungal infection, viral infection, Chagas’ disease • Physical/Trauma: lacerations • Chemical/Toxic: gastro-oesophageal reflux disease (GORD) • Circulatory disturbances: oeophageal varices • Immunological disturbance:eosinophilic oesophagitis • Degenerative disorders • Iatrogenic:pill oesophagitis • Idiopathic:achalasia • Multifactorial • Various: radiation, nutritional deficiency, psychosomatic • Pre-neoplastic/ Neoplastic:Barrett’s oesophagus -> adenocarcinoma squamous cell carcinoma

  34. Eosinophilic oesophagitis • Exposure to allergen -> allergic pattern inflammation (IgE, eosinophils) • Cow’s milk, soy, egg, often unknown • Associated with asthma • Children, young adults

  35. Eosinophilic oesophagitis

  36. Oesophagus: classification by aetiology • Congenital: atresia, stenosis, fistulas, webs • Acquired • Infection:fungal infection, viral infection, Chagas’ disease • Physical/Trauma: lacerations • Chemical/Toxic: gastro-oesophageal reflux disease (GORD) • Circulatory disturbances: oesophageal varices • Immunological disturbance:eosinophilic oesophagitis • Degenerative disorders • Iatrogenic:pill oesophagitis • Idiopathic:achalasia • Multifactorial • Various: radiation, nutritional deficiency, psychosomatic • Pre-neoplastic/ Neoplastic:Barrett’s oesophagus -> adenocarcinoma squamous cell carcinoma

  37. Oesophageal varices • Oesophageal submucosal veins connect portal and systemic venous systems • Normal low pressure gradient between two venous systems (~5mmHg) • If portal venous pressure increases (portal hypertension), gradient increases (>10mmHg) • Increased flow in submucosal veins in oesophagus: Can bleed massively

  38. Oesophageal varices

  39. Oesophagus: classification by aetiology • Congenital: atresia, stenosis, fistulas, webs • Acquired • Infection:fungal infection, viral infection, Chagas’ disease • Physical/Trauma: lacerations • Chemical/Toxic: gastro-oesophageal reflux disease (GORD) • Circulatory disturbances: oeophageal varices • Immunological disturbance:eosinophilic oesophagitis • Degenerative disorders • Iatrogenic:pill oesophagitis • Idiopathic:achalasia • Multifactorial • Various: radiation, nutritional deficiency, psychosomatic • Pre-neoplastic/ Neoplastic:Barrett’s oesophagus -> adenocarcinoma squamous cell carcinoma

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