Enforce of pfysical, chemical and biological factors in pathogenesis of diseases 1.
Pathogenesis of Diseases of the Oesophagus
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Transcript of 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• 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
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
Manometry: normal oesophagus
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
Clinical Endoscopic
Microscopic
Definition of GORD?
Endoscopic appearance
Normal Inflamed
Hiatal Hernia
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
Stricture Ulceration
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
Candida oesophagitis
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
Herpes simplex oesophagitis
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
Mega-oesophagus
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
Eosinophilic oesophagitis
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
Oesophageal varices
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