Pathology of IBD

Question 1

What is the aetiology of UC and CD?

Answer 1

Unknown

Question 2

Which parts of the GI tract are affected by Crohn’s disease?

Answer 2

Anywhere from the mouth to the anus can be affected by Crohn’s.
The most commonly affected sites are the terminal ilium and the colon.

Question 3

Who presents with Crohn’s disease?

Answer 3

Young patients:
50% of patients are 20-30 years old at presentation
90% of patients are 10-40 years old at presentation

Question 4

Is Crohn’s disease more common in males or females?

Answer 4

Males

Question 5

What is the clinical presentation of Crohn’s disease?

Answer 5

Abdominal pain
Small bowel obstruction
Diarrhoea
Bleeding PR
Anaemia
Weight loss

Question 6

Describe the clinical course of Crohn’s disease

Answer 6

It is a chronic disease
There are relapses and remissions
There is an unpredictable response to therapy
There is a subgroup of patients who go into lasting remission within 3 years of diagnosis

Question 7

What investigations are required to diagnose Crohn’s disease?

Answer 7

Endoscopy and mucosal biopsy

Question 8

Describe the macroscopic appearance of the bowel in Crohn’s disease.

Answer 8

Patchy, segmental disease with skip lesions.
The inflammation is transmural and granulomatous.
There are interconnecting deep fissuring ulcers.
The bowel wall is significantly thickened due to oedema and fibrosis, often leading to partial obstruction (this produces a characteristic radiological sign where only a trickle of contrast medium passes through the affected segment.

Question 9

Describe the microscopic appearance of the colon in Crohn’s disease

Answer 9

The inflammation is focal and patchy
It usually involves all layers of the bowel wall
There are lymphoid aggregates and non-caseating (sarcoid-like) granulomas.
Deep Fissuring ulcers that are knife like in appearance
Mesenteric lymph nodes are enlarged and may also contain granulomas
Cryptitis and crypt abscesses

Question 10

What do the granulomas in Crohn’s disease consist of?

Answer 10

Epithelioid macrophages
Langhan’s type giant cells
Surrounded by a cuff of lymphocytes

Question 11

What percentage of Crohn’s patients are found to have granulomas?

Answer 11

50-60%

Question 12

What are complications of Crohn’s disease?

Answer 12

Malabsorption
Iatrogenic short bowel syndrome due to repeated resections and recurrences
Hypoproteinaemia, Vitamin deficiency, Anaemia of all types
Gallstones due to interrupted enterohepatic circulation
Fistulas
Anal disease
Intractable diseas
Bowel obstruction
Perforation
Malignancy
Amyloidosis
Rarely toxic megacolon

Question 13

Which alleles are associated with Crohn’s disease?

Answer 13

HLA-DR1, HLA-DQw5

Question 14

What are possible environmental triggers for Crohn’s disease?

Answer 14

Smoking increases the risk of Crohn’s disease
Infectious agents cause a similar pathology
Vasculitis could explain the segmental distribution
Sterile environment theory

Question 15

Describe the aberrant immune response in Crohn’s disease?

Answer 15

Persistent activation of T-cells and macrophages (failure to switch off)

Excess proinflammatory cytokine production

Maybe alterable by changing intestinal microflora…”Probiotics”

Question 16

What is likely to cause Crohn’s?

Answer 16

A genetic susceptibility to an environmental agent. The defect prevents a controlled and effective immune response to the trigger.

Question 17

Which parts of the GI tracts are affected by Ulcerative Colitis?

Answer 17

It is confined to the rectum and the colon

Question 18

What is UC characterised by?

Answer 18

Diffuse superficial inflammation of the mucosa and submucosa.
Remitting and relapsing
Associated with the passage of blood, mucus and pus

Question 19

What is the commonest cause of diarrhoea with pus and mucus in temperate climates?

Answer 19

Ulcerative colitis

Question 20

Which patients present with UC?

Answer 20

Mostly young patients- peaks in the thirties.
It can present in the elderly and can occur in children.
It is more common in males.

Question 21

How does UC progress?

Answer 21

The disease usually begins distally involving the rectum (ulcerative proctitis) and extends in a continuous fashion proximally to varying extent.

Question 22

Describe the clinical course of UC

Answer 22

Chronic
Exacerbation and remission
Continuous low grade activity
Acute fulminant colitis (toxic megacolon) can occur

Question 23

How is UC diagnosed?

Answer 23

Endoscopy and mucosal biopsy

Question 24

What does UC look like macroscopically?

Answer 24

The ulcers are shallow and irregular in outline
They become confluent and extent horizontally to undermine adjacent, less involved mucosa.
The ulceration usually only involves the mucosa and the submucosa.
In severe cases, there is extension into the main muscle coats and perforation may occur.
There is intense hyperaemia of the intact mucosa and haemorrhage from the ulcers.
Pseudopolyps may be seen

Question 25

Describe the microscopic appearance of UC.

Answer 25

The inflammation is diffuse and limited to the mucosa.
Polymorphs are seen in the lamina propria, in the crypt epithelium and as aggregates within distended crypts (crypt abscesses).
There are numerous plasma cells at the base of the mucosa- basal plasmacytosis- this is a key finding of UC.
Crypts are often destroyed during the acute phase and are often regenerated by branching or dilatation and may no longer reach up to the muscularis mucosae.

Question 26

How can UC be diagnosed in a non-acute inflammatory phase?

Answer 26

By the distortion of the architecture.
Colorectal biopsy will reveal crypt atrophy with distortion, replacement fibrosis and metaplastic features such as the presence of Paneth cells.

Question 27

Are there granulomas in UC?

Answer 27

No

Question 28

What are complications of UC?

Answer 28

Intractable disease
Toxic megacolon 
Colorectal carcinoma- chronic inflammation leads to epithelial dysplasia then carcinoma
Blood loss
Electrolyte disturbance (hypokalaemia)
Anal fissures (not common)

Question 29

What are extra-GI manifestations of UC?

Answer 29

Eyes: Uveitis
Liver: Primary sclerosing cholangitis
Joints: Arthritis, ankylosing spondylitis
Skin: Pyoderma gangrenosum, erythema nodosum

Question 30

Which allele is associated with UC?

Which gene are familial cases associated with?

Answer 30

HLA-DR2

NOD-2

Question 31

Describe the aberrant immune response in UC.

Answer 31

Persistent activation of T-cells and macrophages
Autoantibodies eg ANCA present
Excess proinflammatory cytokine production and bystander damage due to neutrophillic inflammation
Maybe alterable by changing intestinal microflora…”Probiotics”