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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 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 • Degenerative disorders • Iatrogenic • Idiopathic • Multifactorial • Various: radiation, nutritional deficiency, psychosomatic • Pre-neoplastic/ Neoplastic
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
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
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
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%
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
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
Gastro-Oesophageal Reflux Disease (GORD) • Hydrochloric acid and pepsin • -> H+ ions diffuse into cells • -> acidification of mucosa • -> inflammation, necrosis
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
Definition of GORD? Clinical Endoscopic Microscopic
Endoscopic appearance Normal Inflamed
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
Complications of GORD • Ulceration • Haemorrhage • Perforation • Fibrotic stricture • Aspiration • Barrett’s oesophagus • risk of dysplasia and malignancy
Complications of GORD Ulceration Stricture
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
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
Fungal infection • Usually Candida • Normal oral flora • Colonises, proliferates in oesophagus • Debilitated patients • Immunosuppressed (steroids, HIV, other) • Broad spectrum antibiotics • Inflammation, erosions, ulceration
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
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
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
Manometry in achalasia Normal Achalasia
Achalasia • Dysphagia, pain • Food bolus stuck • Aspiration • Mega-oesophagus • Risk of squamous cell carcinoma
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
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
Pill oesophagitis • Chemical injury • Pill temporarily held up in oesophagus • Contact time • Chemical nature of medication • Size, solubility, coating • Common with KCl, NSAIDs
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
Eosinophilic oesophagitis • Exposure to allergen -> allergic pattern inflammation (IgE, eosinophils) • Cow’s milk, soy, egg, often unknown • Associated with asthma • Children, young adults
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
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
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