Lecture 15 - Ulcerative Colitis & Crohn's Disease Flashcards
1
Q
What are the various categories of ulcer-inflammatory conditions of the bowel?
A
- Infective
• viral
• bacterial
• parasitic - Non-infective
• IBD (inflammatory bowel disease)
• Enterocolitis
2
Q
What are some viral causes of ulcer-inflammatory conditions of the bowel?
A
Rotavirus
Norovirus
3
Q
What are some bacterial causes of ulcer-inflammatory conditions of the bowel?
A
- E. coli
* Clostridium difficile
4
Q
What are some parasitic causes of ulcer-inflammatory conditions of the bowel?
A
- Giardia lamblia
* Schistosomiasis
5
Q
What are the two major forms of IBD?
A
(Inflammatory bowel disease)
• Ulcerative colitis
• Crohn’s disease
6
Q
Characterise IBD
A
- Chronic inflammatory
* Ulcerative
7
Q
What is the underlying cause of IBD?
A
Dysregulated & over-active immune response to microflora in the bowel
8
Q
What are the clinical symptoms of IBD?
A
- Rectal bleeding (in UC)
- Diarrhoea
- Abdominal pain
- Fever
9
Q
What is the defining feature of ulcerative colitis?
A
Involvement of the rectal mucosa
10
Q
What are the systemic effects of UC?
A
- Fever
- Arthralgia
- Inflammation of the eye
11
Q
Describe the macroscopic changes to the rectal mucosa in UC
A
- Shallow ulceration
- Hyperaemic
- Loss of haustra
- Pseudopolyps
- Narrowing of lumen
- Shortening of colon
- Granular mucosa
- Diffusely inflamed
12
Q
What is granular mucosa?
A
- Roughened (not smooth) or sometimes reddish macroscopic appearance of the mucosa
- Due to the inflammation
13
Q
What does hyperaemic mean?
A
Increased blood flow
14
Q
Explain Pseudopolyps
A
- Mucosal bridges form initially
- Later re-epithelialise as healing occurs
- Resembles polyps
15
Q
What are the microscopic changes in UC?
A
- Goblet cell loss
- Hyperplasia of epithelium
- Neutrophil infiltration of crypts
- Chronic inflammatory cells in lamina propria
- Vascular congestion
- Loss of epithelium; ulceration
- Luminal pus
- Distorted tubular architecture
16
Q
Describe normal tubular architecture
A
- Tubules extend completely across mucosa down to the muscularis mucosae
- Parallel tubules
- Uniformly spaced
- Goblet cells present
- Low levels of chronic inflammatory cells in lamina propria
17
Q
What is the effect of loss of goblet cells?
A
Loss of mucin
18
Q
Describe tubular architecture in UC
A
- Distorted tubular architecture
- Crypt abscesses
- Inflamed tubules
- Dense inflammatory infiltrate in LP
- Eroded surface epithelium
19
Q
Describe microscopic tissue features of UC remission
A
- Tubular branching
- Shortened tubules
- Paneth cell metaplasia
- Thickened muscularis mucosae
- Epithelial dysplasia
20
Q
Describe dysplasia in IBD
Describe the histological features
A
- Abnormal cellular and architectural alterations
- Confined to the mucosa by basement membrane
Cells show: • Loss of mucin • Nuclear enlargement • Nuclear pleomorphism • Loss of polarity; nucleus not in a defined position • Pseudostratification • Abnormal mitoses
21
Q
What is pleomorphism?
A
Nuclear shape and size variation
22
Q
What are the risk factors for developing malignancies in UC?
A
- UC onset in childhood
- Disease longer than 10 years in duration
- Extent of pancolitis
23
Q
What is pancolitis?
A
Extensive spread of UC throughout the large intestine to the ileocloacal junction
24
Q
Describe the surveillance for malignancy in people with UC.
What happens if there is high grade dysplasia identified?
A
Annual colonoscopy w/ biopsy after 7 years with the disease
Colectomy if there is high grade dysplasia / carcinoma identified
25
What are the complications of UC?
```
Local complications
• Bleeding
• Malignancy
• Perferations (if deep ulceration)
• Toxic megacolon
```
* Damage to bile ducts
* Arthritis
26
Characterise Crohn's disease very generally
Chronic inflammatory condition of the alimentary tract
27
Which regions can be affected in Crohn's disease?
Potentially any part of the alimentary canal, but mostly:
Ileocolic: 45%
• distal small intestine
• proximal large intestine
Small bowel alone 33%
Colon alone 20%
28
What are the clinical features of CD?
* Fever, abdominal pain, diarrhoea
* Fistula formation
* Strictures
29
What is a fistula?
Abnormal passage between two hollow organs
30
What are strictures?
Abnormal narrowing of a passage
31
What are the macroscopic features of CD?
* Fistula formation
* Aphthoid ulcers (small, discrete ulcers)
* Strictured segments
* Fat wrapping
* Thickened, indurated wall of the intestine
* Fissures (cleft ulcers)
* Oedema → cobbled appearance
* Enlarged LNs
* 'Skip lesions'
* Serositis
32
Describe fat wrapping
Extension of mesenteric fat around the intestine
| 'creeps over the wall' of the intestine
33
What is ileitis?
Inflammation of the ileum
34
What are some microscopic features of CD?
* Ileitis (transmural inflammation)
* Oedema
* Granulomas; multinucleate giant cells
* Pyloric gland metaplasia
35
```
Compare the macroscopic features of UC and CD:
• Areas affected
• Ileum
• Ulceration
• Fissuring
• Serosa
• Fat wrapping
• Wall thickness
• Shortening
• Strictures
• Fistulae
• Pseudopolypsis
• Anal lesions
• Malignancy
• Systemic complications
```
Areas affected: UC: continuous, CD: skip lesions
Ileum: UC: not involved, CD: commonly involved
Ulceration: present in both, UC: CD: cobble stone appearance
Fissuring: UC: - , CD: +
Serositis: UC: - , CD: +
Fat wrapping: UC: - , CD: +
Wall thickness: UC: normal, CD: oedematous, thick
Shortening: UC: due to muscle hypertrophy, CD: due to fibrosis
Strictures: UC: - , CD: +
Fistulae: UC: - , CD: +
Pseudopolypsis: UC: + , CD: -
Anal lesions: UC: - , CD: +
Malignancy: seen in both, but increased risk with UC
Systemic complications: similar in both: liver, eyes, skin, joints
36
Describe 'skip lesions'
Segmental lesions
| • seen in CD: some areas are affected, with intervening normal regions
37
What happens to the muscularis mucosae in UC?
Hypertrophy → shortening of colon
38
Is malignancy common in UC and CD?
UC: 30-fold increased risk compared to general population
CD: 6-fold increased risk
39
In what organs are systemic complications seen in UC and CD?
* Joints
* Eyes
* Skin
* Liver
40
```
Compare the macroscopic features of UC and CD:
• Paneth cell metaplasia
• Pyloric metaplasia
• Granulomas
• Fissures
• Epithelial dysplasia
• Anal lesions
```
Paneth cell metaplasia: UC: + , CD: -
Pyloric metaplasia: UC: - , CD: +
Granulomas: UC: - , CD: +
Fissures: UC: - , CD: +
Epithelial dysplasia: UC: in non-inflamed mucosa, CD: -
Anal lesions: CD: granulomas present
41
What are the three things that can lead to IBD?
* Presence of Luminal antigens
* Genetic susceptibility
* Environmental triggers
42
What is the genetic basis of IBD?
Genetic inheritance is more common in CD
| Less common in UC
43
```
What are the effects of the following on UC and CD in terms of risk?
• Smoking
• Appendectomy
• High sanitation in childhood
• High intake of refined carbohydrates
• Perinatal infection
• Breast feeding
• Oral contraceptive use
```
Smoking: UC: decreases, CD: increases
Appendectomy : UC: decreases, CD: 0
High sanitation in childhood : UC: 0, CD: increases
High intake of refined carbohydrates : UC: 0, CD: increases
Perinatal infection: UC: ? , CD: increases
Breast feeding: UC: decreases ? , CD: ?
Oral contraceptive use: UC: increases ? , CD: ?
44
What are the different types of Th cell that can be stimulated?
How are the different types stimulated?
What are the various types associated with?
Different combination of cytokine release from APCs dictates the type of Th cell
Th1: cell mediated granulomas, CD
Th2: hypersensitivity, UC
Treg: tolerance
45
How much bacteria are there in our gut?
2 kgs
| Bacteria make up 50% of the dry weight of faeces
46
Describe the muscle in the large intestine
The bands of longitudinal muscle
This allows some redundancy; if need be the large intestine can be lengthened
When tho muscle is contracted, haustra are formed.
47
Why are pseudopolyps important?
They can lead to malignancies
48
Describe wall thickness in UC and CD
UC: Normal thickness
CD: thickened
49
At a tissue level, what is affected in UC?
| Compare this with CD
UC: restricted to the mucosa.
Muscular propria and submucosa unaffected
CD: not restricted to the mucosa. All of the layers will be inflamed
50
Compare intestinal narrowing in UC and CD
UC: due to muscularis mucosae hypertrophy
CD: due to fibrosis of the wall
51
What is the significance of the nodules in the large bowel in UC?
This is the initial stage of dysplasia, and leads to malignancy
52
What happens after 10 years of UC disease?
Rapidly increasing risk of malignancy
53
What is toxic megacolon?
Dilation of the colon
| due to inflammation of muscle layer
54
Describe fissures
Complete thickness of tissue inflamed, spreading through to adjacent structures
55
Describe fissuring ulcers
Very sharp, looks like a thorn that goes right through the wall.
Fibrin forms on outer surface, causing the neighbouring organs to stick to the inflamed organ
Inflammation spreads to this neighbouring tissue
56
What is meant by transmural inflammation?
| In which disorders is it seen?
Seen in CD, not UC
The entire extent of the wall thickness is inflamed
57
What causes megacolon?
| In which disorders is it seen?
Entire muscle axis inflamed
Seen in UC, not CD
58
Which diseases exhibits 'skip' lesions?
CD
59
What is the effect of serositis?
The inflamed organs sticks to neighbouring (healthy) organs
60
What causes cobble stone areas?
| Which disease is it seen in?
Lymphoedema
There is blockage of lymphatics, so that the tissue can no longer drain lymph
Seen in CD
61
Which cytokine released by APCs leads to UC?
IL-4
| Stimulates Th2
62
Describe the response to gut microflora in normal cases.
| Describe how this can be changed, leading to disease
Normal:
• peptidoglycan of bacteria stimulates TLR2
• NOD2 inhibits the intracellular transduction cascade
• No expression of IL-12
• No inflammation
```
Crohn's disease
• Peptidoglycan stimulates TLR
• Intracellular transduction cascade
• Expression of IL-12
• Chronic inflammation
• Crohn's disease
```
63
What is the role of M cells?
| Where are they found?
They are found in Peyer's patches, interspersed between the epithelial cells
Role:
• Translocate bacterial peptides from the luminal contents for exposure to APCs in the sub-epithelial dome
64
What sort of response does one get when APCs release mainly IL-12?
Th1
65
What sort of response does one get when APCs release mainly IL-10?
Treg
66
What sort of response does one get when APCs release mainly IL-4?
Th2
67
Describe how tolerance can break down in the gut mucosa
* Excess secretion of IL-12
* Increased Th1 response, decreased Treg
* Pro-inflammatory; lymphoid & macrophage proliferation
* Inhibition of apoptosis of lymphocytes
* Crohn's disease
