Pathology of IBD Flashcards
What is the aetiology of UC and CD?
Unknown
Which parts of the GI tract are affected by Crohn’s disease?
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.
Who presents with Crohn’s disease?
Young patients:
50% of patients are 20-30 years old at presentation
90% of patients are 10-40 years old at presentation
Is Crohn’s disease more common in males or females?
Males
What is the clinical presentation of Crohn’s disease?
Abdominal pain Small bowel obstruction Diarrhoea Bleeding PR Anaemia Weight loss
Describe the clinical course of Crohn’s disease
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
What investigations are required to diagnose Crohn’s disease?
Endoscopy and mucosal biopsy
Describe the macroscopic appearance of the bowel in Crohn’s disease.
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.
Describe the microscopic appearance of the colon in Crohn’s disease
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
What do the granulomas in Crohn’s disease consist of?
Epithelioid macrophages
Langhan’s type giant cells
Surrounded by a cuff of lymphocytes
What percentage of Crohn’s patients are found to have granulomas?
50-60%
What are complications of Crohn’s disease?
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
Which alleles are associated with Crohn’s disease?
HLA-DR1, HLA-DQw5
What are possible environmental triggers for Crohn’s disease?
Smoking increases the risk of Crohn’s disease
Infectious agents cause a similar pathology
Vasculitis could explain the segmental distribution
Sterile environment theory
Describe the aberrant immune response in Crohn’s disease?
Persistent activation of T-cells and macrophages (failure to switch off)
Excess proinflammatory cytokine production
Maybe alterable by changing intestinal microflora…”Probiotics”
What is likely to cause Crohn’s?
A genetic susceptibility to an environmental agent. The defect prevents a controlled and effective immune response to the trigger.
Which parts of the GI tracts are affected by Ulcerative Colitis?
It is confined to the rectum and the colon
What is UC characterised by?
Diffuse superficial inflammation of the mucosa and submucosa.
Remitting and relapsing
Associated with the passage of blood, mucus and pus
What is the commonest cause of diarrhoea with pus and mucus in temperate climates?
Ulcerative colitis
Which patients present with UC?
Mostly young patients- peaks in the thirties.
It can present in the elderly and can occur in children.
It is more common in males.
How does UC progress?
The disease usually begins distally involving the rectum (ulcerative proctitis) and extends in a continuous fashion proximally to varying extent.
Describe the clinical course of UC
Chronic
Exacerbation and remission
Continuous low grade activity
Acute fulminant colitis (toxic megacolon) can occur
How is UC diagnosed?
Endoscopy and mucosal biopsy
What does UC look like macroscopically?
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
Describe the microscopic appearance of UC.
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.
How can UC be diagnosed in a non-acute inflammatory phase?
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.
Are there granulomas in UC?
No
What are complications of UC?
Intractable disease Toxic megacolon Colorectal carcinoma- chronic inflammation leads to epithelial dysplasia then carcinoma Blood loss Electrolyte disturbance (hypokalaemia) Anal fissures (not common)
What are extra-GI manifestations of UC?
Eyes: Uveitis
Liver: Primary sclerosing cholangitis
Joints: Arthritis, ankylosing spondylitis
Skin: Pyoderma gangrenosum, erythema nodosum
Which allele is associated with UC?
Which gene are familial cases associated with?
HLA-DR2
NOD-2
Describe the aberrant immune response in UC.
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”
