Lecture 15 - Ulcerative Colitis & Crohn's Disease Flashcards Preview

PATH30001 - Mechanisms of Disease > Lecture 15 - Ulcerative Colitis & Crohn's Disease > Flashcards

Flashcards in Lecture 15 - Ulcerative Colitis & Crohn's Disease Deck (67):
1

What are the various categories of ulcer-inflammatory conditions of the bowel?

1. Infective
• viral
• bacterial
• parasitic

2. Non-infective
• IBD (inflammatory bowel disease)
• Enterocolitis

2

What are some viral causes of ulcer-inflammatory conditions of the bowel?

Rotavirus
Norovirus

3

What are some bacterial causes of ulcer-inflammatory conditions of the bowel?

• E. coli
• Clostridium difficile

4

What are some parasitic causes of ulcer-inflammatory conditions of the bowel?

• Giardia lamblia
• Schistosomiasis

5

What are the two major forms of IBD?

(Inflammatory bowel disease)
• Ulcerative colitis
• Crohn's disease

6

Characterise IBD

• Chronic inflammatory
• Ulcerative

7

What is the underlying cause of IBD?

Dysregulated & over-active immune response to microflora in the bowel

8

What are the clinical symptoms of IBD?

• Rectal bleeding (in UC)
• Diarrhoea
• Abdominal pain
• Fever

9

What is the defining feature of ulcerative colitis?

Involvement of the rectal mucosa

10

What are the systemic effects of UC?

• Fever
• Arthralgia
• Inflammation of the eye

11

Describe the macroscopic changes to the rectal mucosa in UC

• Shallow ulceration
• Hyperaemic
• Loss of haustra
• Pseudopolyps
• Narrowing of lumen
• Shortening of colon
• Granular mucosa
• Diffusely inflamed

12

What is granular mucosa?

• Roughened (not smooth) or sometimes reddish macroscopic appearance of the mucosa
• Due to the inflammation

13

What does hyperaemic mean?

Increased blood flow

14

Explain Pseudopolyps

• Mucosal bridges form initially
• Later re-epithelialise as healing occurs
• Resembles polyps

15

What are the microscopic changes in UC?

• 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

Describe normal tubular architecture

• 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

What is the effect of loss of goblet cells?

Loss of mucin

18

Describe tubular architecture in UC

• Distorted tubular architecture
• Crypt abscesses
• Inflamed tubules
• Dense inflammatory infiltrate in LP
• Eroded surface epithelium

19

Describe microscopic tissue features of UC remission

• Tubular branching
• Shortened tubules
• Paneth cell metaplasia
• Thickened muscularis mucosae
• Epithelial dysplasia

20

Describe dysplasia in IBD
Describe the histological features

• 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

What is pleomorphism?

Nuclear shape and size variation

22

What are the risk factors for developing malignancies in UC?

• UC onset in childhood
• Disease longer than 10 years in duration
• Extent of pancolitis

23

What is pancolitis?

Extensive spread of UC throughout the large intestine to the ileocloacal junction

24

Describe the surveillance for malignancy in people with UC.
What happens if there is high grade dysplasia identified?

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