Pathogenesis of Diseases of the Oesophagus

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Pathogenesis of Diseases of the Oesophagus

• Dr Paul L. Crotty
• Departement of Pathology
• AMNCH, Tallaght
• October 2008

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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

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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

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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 Barretts oesophagus
  -gt adenocarcinoma squamous cell carcinoma

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Normal Oesophagus
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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

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Manometry normal oesophagus
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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

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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

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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

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Gastro-Oesophageal Reflux Disease (GORD)

• Hydrochloric acid and pepsin
• -gt H ions diffuse into cells
• -gt acidification of mucosa
• -gt inflammation, necrosis

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Gastro-Oesophageal Reflux Disease (GORD)

• Clinical symptoms of heartburn
• Endoscopic red/congested mucosa
• Manometric decreased sphincter pressure
• pH number, duration of dips pHlt4
• Pathological microscopic evidence of oesophagitis

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Definition of GORD?
Clinical
Endoscopic
Microscopic
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Endoscopic appearance
Normal
Inflamed
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Hiatal Hernia
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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

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Complications of GORD

• Ulceration
• Haemorrhage
• Perforation
• Fibrotic stricture
• Aspiration
• Barretts oesophagus
• risk of dysplasia and malignancy

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Complications of GORD
Ulceration
Stricture
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Barretts 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

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Barretts oesophagus

• Long segment (gt3cm)
• Short segment (lt3cm)
• Risk of adenocarcinoma in long segment disease is
  30-40X the general population risk
• Risk is proportional to length of disease
• Surveillance programmes

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Fungal infection

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

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Candida oesophagitis
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Viral infection

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

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Herpes simplex oesophagitis
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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 Barretts oesophagus
  -gt adenocarcinoma squamous cell carcinoma

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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

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Manometry in achalasia
Normal
Achalasia
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Achalasia

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

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Chagass 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

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Mega-oesophagus
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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 Barretts oesophagus
  -gt adenocarcinoma squamous cell carcinoma

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Pill oesophagitis

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

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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 Barretts oesophagus
  -gt adenocarcinoma squamous cell carcinoma

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Eosinophilic oesophagitis

• Exposure to allergen -gt allergic pattern
  inflammation (IgE, eosinophils)
• Cows milk, soy, egg, often unknown
• Associated with asthma
• Children, young adults

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Eosinophilic oesophagitis
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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 Barretts oesophagus
  -gt adenocarcinoma squamous cell carcinoma

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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 (gt10mmHg)
• Increased flow in submucosal veins in oesophagus
  Can bleed massively

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Oesophageal varices
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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 Barretts oesophagus
  -gt adenocarcinoma squamous cell carcinoma