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