Path Notes: Idiopathic Bowel Disease***

Question 1

What are the idiopathic bowel diseases? What are they both, in general?

Answer 1

Ulcerative Colitis and Crohn’s DIsease

Both are chronic, relapsing conditions of the bowel

Resulting from inappropriate and persistent activation of the mucosal immune system, for unknown reasons

Question 2

Describe the pathological spread of UC and Crohn’s. What are a couple of features they have in common?

Answer 2

Crohn’s:

• May affect any portion of the GIT from oesophagus to anus
• Most often involves distal SI and colon
• Typically transmural

UC:

• Limited to colon and rectum
• Typically extends only into mucosa and submucosa

Both have extra-intestinal inflammatory manifestations

Both are more common in females, and they frequently present in the teens/early 20s

Question 3

List the aeitiology/pathogenesis of both Crohn’s and UC:

Answer 3

1. Hygeine hypothesis
2. Defects in host interactions with intestinal microbiota
3. Intestinal epithelial dysfunction
4. Abherrent intestinal mucosal immune response

Question 4

Describe the hygeine hypothesis for inflammatory bowel disease

Answer 4

1. Reduced frequency of intestinal infections results in inadequate development of regulators of mucosal immune responses
2. This enables pathogens, that should only trigger self-limiting reactions, to trigger strong immune responses and inflammatory bowel disease in susceptible people

Question 5

Describe Defects in host interactions with intestinal microbiota

Answer 5

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Question 6

Describe Intestinal epithelial dysfunction and how it causes IBS

Answer 6

1. Dysfunction of intestinal tight barrier
2. Defective transepithelial transport
3. Defective extracellular mucin barrier
4. Paneth cell granule abnormalities

Question 7

Describe ‘Abherrent mucosal immune response’ with regard to IBS

Answer 7

1. High levels of T-cell activation
2. Lack of regulatory T-cell action
3. UC and CD thought to involve different specific T-cells*

Question 8

What are the hereditary factors regarding IBS?

Answer 8

1. 15% of IBS sufferers have 1st degree relatives who are affected
2. Monozygotic twins have 30-50% concordance rate in CD, and 15% concordance in UC
3. HLA associations
4. NOD-2 gene associated with CD

Question 9

Explain what NOD-2 has to do with CD?

Answer 9

1. NOD-2 encodes for a protein that binds bacterial peptidoglycans
2. Some variants of the gene may lead to inaffective / less-effective binding, enabling bacteria to get into lamina propria more easily, and incite an inflammatory response
3. NOD-2 variants are perhaps involved in regulating host immune response to intestinal microbia to prevent excessive immune activation
4. More genes are being recognised*

Question 10

What is the basis for diagnosis of IBS?

Answer 10

1. History
2. Examination
3. Lab findings
4. Bowel biopsy