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):

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


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



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

• E. coli
• Clostridium difficile


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

• Giardia lamblia
• Schistosomiasis


What are the two major forms of IBD?

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


Characterise IBD

• Chronic inflammatory
• Ulcerative


What is the underlying cause of IBD?

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


What are the clinical symptoms of IBD?

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


What is the defining feature of ulcerative colitis?

Involvement of the rectal mucosa


What are the systemic effects of UC?

• Fever
• Arthralgia
• Inflammation of the eye


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


What is granular mucosa?

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


What does hyperaemic mean?

Increased blood flow


Explain Pseudopolyps

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


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


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


What is the effect of loss of goblet cells?

Loss of mucin


Describe tubular architecture in UC

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


Describe microscopic tissue features of UC remission

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


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


What is pleomorphism?

Nuclear shape and size variation


What are the risk factors for developing malignancies in UC?

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


What is pancolitis?

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


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


What are the complications of UC?

Local complications
• Bleeding
• Malignancy
• Perferations (if deep ulceration)
• Toxic megacolon

• Damage to bile ducts
• Arthritis


Characterise Crohn's disease very generally

Chronic inflammatory condition of the alimentary tract


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%


What are the clinical features of CD?

• Fever, abdominal pain, diarrhoea
• Fistula formation
• Strictures


What is a fistula?

Abnormal passage between two hollow organs


What are strictures?

Abnormal narrowing of a passage


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


Describe fat wrapping

Extension of mesenteric fat around the intestine
'creeps over the wall' of the intestine


What is ileitis?

Inflammation of the ileum


What are some microscopic features of CD?

• Ileitis (transmural inflammation)
• Oedema
• Granulomas; multinucleate giant cells
• Pyloric gland metaplasia


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


Describe 'skip lesions'

Segmental lesions
• seen in CD: some areas are affected, with intervening normal regions


What happens to the muscularis mucosae in UC?

Hypertrophy → shortening of colon


Is malignancy common in UC and CD?

UC: 30-fold increased risk compared to general population
CD: 6-fold increased risk


In what organs are systemic complications seen in UC and CD?

• Joints
• Eyes
• Skin
• Liver


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


What are the three things that can lead to IBD?

• Presence of Luminal antigens
• Genetic susceptibility
• Environmental triggers


What is the genetic basis of IBD?

Genetic inheritance is more common in CD
Less common in UC


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: ?


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


How much bacteria are there in our gut?

2 kgs
Bacteria make up 50% of the dry weight of faeces


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.


Why are pseudopolyps important?

They can lead to malignancies


Describe wall thickness in UC and CD

UC: Normal thickness

CD: thickened


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


Compare intestinal narrowing in UC and CD

UC: due to muscularis mucosae hypertrophy
CD: due to fibrosis of the wall


What is the significance of the nodules in the large bowel in UC?

This is the initial stage of dysplasia, and leads to malignancy


What happens after 10 years of UC disease?

Rapidly increasing risk of malignancy


What is toxic megacolon?

Dilation of the colon
(due to inflammation of muscle layer)


Describe fissures

Complete thickness of tissue inflamed, spreading through to adjacent structures


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


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


What causes megacolon?
In which disorders is it seen?

Entire muscle axis inflamed

Seen in UC, not CD


Which diseases exhibits 'skip' lesions?



What is the effect of serositis?

The inflamed organs sticks to neighbouring (healthy) organs


What causes cobble stone areas?
Which disease is it seen in?

There is blockage of lymphatics, so that the tissue can no longer drain lymph

Seen in CD


Which cytokine released by APCs leads to UC?

Stimulates Th2


Describe the response to gut microflora in normal cases.
Describe how this can be changed, leading to disease

• 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


What is the role of M cells?
Where are they found?

They are found in Peyer's patches, interspersed between the epithelial cells

• Translocate bacterial peptides from the luminal contents for exposure to APCs in the sub-epithelial dome


What sort of response does one get when APCs release mainly IL-12?



What sort of response does one get when APCs release mainly IL-10?



What sort of response does one get when APCs release mainly IL-4?



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