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Inflammatory Bowel Disease Flashcards

1
Q

What are inflammatory bowel diseases?

What are the 2 types?

A

Chronic relapsing and remitting inflammatory disorders of unknown aetiology

  1. Crohn’s disease
  2. Ulcerative colitis
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2
Q

What age group tends to be affected by IBD?

What is the cure?

A

Tends to affect people aged 15-40

There is no cure for Crohn’s disease but ulcerative colitis can be cured by surgical removal of the colon

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3
Q

What parts of the body are affected by ulcerative colitis?

A

It is restricted to the colon and the rectum

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4
Q

What parts of the body are affected by Crohn’s disease?

A

It can affect anywhere from the mouth to anus

The majority of cases start in the terminal ileum

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5
Q

What are the 2 main complications of Crohn’s disease that are difficult to treat?

A
  1. perianal disease

2. fistulation

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6
Q

What is meant by oral tolerance?

A

This is the suppression of immune responses to antigens that have previously been administered via the oral route

e.g. harmless antigens in food

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7
Q

How does IBD occur?

A

If there is an immune response to a harmless antigen, this can lead to chronic activation of the immune system

This leads to chronic inflammation

There is a failure to maintain oral tolerance

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8
Q

What is increased susceptibility to Crohn’s disease associated with?

A

Mutations in the NOD2 gene

This is involved in intracellular processing of bacterial antigens

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9
Q

What is increased susceptibility to BOTH ulcerative colitis and Crohn’s disease associated with?

A

Polymorphisms in IL-23

This is involved in regulation of Th-1 and Th-17 cell differentitation

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10
Q

What are the exogenous triggers of IBD?

A

Environmental factors, such as commensal bacteria and their products

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11
Q

What is the largest independent risk factor for IBD?

A

A positive family history

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12
Q

Why can fistulae only happen in Crohn’s disease?

A

The inflammation is transmural

This means that is passes through all 3 layers of bowel lining

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13
Q

In ulcerative colitis, what is:

i. histology
ii. smoking
iii. surgery
iv. recurrence after surgery

A

i. confined to the mucosa/sub-mucosa
ii. improves condition
iii. pan-proctocolectomy +/- pouch
iv. no

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14
Q

IN Crohn’s disease, what is:

i. histology
ii. smoking
iii. surgery
iv. recurrence after surgery

A

i. transmural
ii. worsens condition
iii. depends on distribution
iv. common

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15
Q

What is the most common extraintestinal manifestation of IBD?

A

Stricturing (often of the bile ducts)

This involves narrowing of the GI tract due to development of scar tissue

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16
Q

What are the musculoskeletal EIMs of IBD?

A
  1. peripheral arthritis
  2. sacroilitis
  3. ankylosing spondylitis
  4. osteoporosis
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17
Q

What are the dermatological EIMs of IBD?

A
  1. erythema nodosum
  2. pyoderma gangrenosum
  3. aphthous stomatitis
  4. sweet syndrome
  5. cutaneous Crohn’s
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18
Q

What are the 6 steps involved in diagnosing IBD?

A
  1. taking a history
  2. physical examination (tender abdomen)
  3. basic tests for anaemia and markers of inflammation
  4. endoscopic tests
  5. radiological tests
  6. confirming the pathology using biopsies
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19
Q

What test is used to look for markers of inflammation?

A

The main marker of inflammation is C-reactive protein (CRP)

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20
Q

What other test is performed to look for markers of inflammation in IBD?

A

Stool tests for calprotectin

This is released from the cytoplasm of neutrophils and is elevated in inflammation

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21
Q

What types of endoscopic tests are performed when diagnosing IBD?

A
  1. sigmoidoscopy
  2. colonoscopy
  3. gastroscopy

This involves taking biopsies

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22
Q

What is a capsule endoscopy?

A

The patient swallows a capsule which takes a continuous video as it passes through the GI tract

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23
Q

What radiological tests are used in diagnosing IBD?

A
  1. barium studies
  2. CT
  3. MRI
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24
Q

What are the 3 types of ulcerative colitis and what parts of the colon do they affect?

A
  1. proctitis - only affects the rectum
  2. left-sided colitis - affects the rectum and descending colon
  3. pan-colitis - affects the entire colon
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25
What are the 5 symptoms of ulcerative colitis?
1. diarrhoea with mucous + blood 2. urgency 3. weight loss 4. abdominal pain/cramps 5. nocturnal symptoms
26
What are the clinical signs of ulcerative colitis?
1. tender abdomen 2. tachycardia 3. pyrexia (fever) 4. extra-intestinal manifestations
27
How can an abnormal colon be seen on an X-ray? What is the fear associated with this?
The colon is distended Haustral folds are not visible - it looks smooth When the colon is distended, there is fear of perforation
28
What types of features may be seen on a endoscopy for ulcerative colitis?
1. granular mucosa 2. spontaneous bleeding 3. deep ulcers
29
Where is inflammation found in ulcerative colitis? What may develop as a result of inflammation?
Inflammation is confined to the colon Inflammation is continuous and affects only the mucosa and submucosa Pseudo-polyps may develop
30
What may a barium enema show in an ulcerative colitis patient?
1. mucosal thickening 2. areas of mucosal loss 3. visible ulcers (particularly in the descending colon where they have a typical undercut edge)
31
What is seen in an endoscopy for Crohn's disease?
1. ileal ulcers 2. erythema 3. inflammation
32
What is erythema? What is is caused by?
Redness of the skin or mucous membranes Caused by hyperaemia - increased blood flow - in superficial capillaries
33
Which parts of the colon are affected by Crohn's disease?
It can affect any part of the GI tract, but commonly the colon and ileum
34
What are the typical features of Crohn's disease?
1. discontinuous inflammation 2. transmural 3. with granulomas
35
Why does Crohn's disease show "discontinuous inflammation"?
There are patches of normal bowel between the inflamed areas
36
How are IBDs mediated?
They are autoimmune and CD4+ helper T-cell mediated Crohn's is associated with a Th1 response UC is associated with a Th2 response
37
What is the initiating stimulus in IBD? Why?
It results from a lack of oral tolerance to commensal bacterial antigens in the gut It is the commensal gut flora that are the initiating stimulus
38
What is the balance involved in tolerance?
Tolerance involves a balance between T helper cells (Th1, Th2, Th17) and T regulatory cells
39
What happens if the balance between T-helper cells and T-regulatory cells is disrupted?
More T-regulatory leads to opportunistic infection More T-helper leads to inflammation and tissue damage
40
Why does having too many T-regulatory cells lead to opportunistic infection?
There is a risk of suppressing the immune system
41
What are the main drugs used to treat IBD? What are the problems with them?
1. steroids - cannot be used long-term | 2. mesalazines - better for treating UC
42
What are the immunomodulator drugs used to treat IBD?
1. azathioprine - used for Crohn's and UC 2. methotrexate - used for both but mainly UC 3. ciclosporin - only used for severe UC
43
What biologics are used to treat IBD?
1. Anti-TNF is used for both, but is better for UC | 2. Vedolizumab is used for both
44
When are steroids used in IBD treatment and why?
They bring inflammation under control quickly and early-on Their side effects mean they are not suitable for long-term use
45
What are steroids then replaced by?
Mesalazines or immunomodulators Mesalazines are only really used in UC
46
What are biologics?
Drugs that target certain cytokines and elements of the inflammatory cascade to prevent inflammation
47
What are the main complications of Crohn's disease? How are they treated?
1. abscess 2. fistula 3. perforation 4. stricture 5. cancer They cannot be treated through medical intervention, so must be treated surgically
48
What can dampening down inflammation do in Crohn's disease? What happens if inflammation persists?
Dampening down inflammation tends to relieve strictures If inflammation persists, scar tissue develops that must be removed surgically
49
What are the steps involved in 'step up' treatment of Crohn's disease?
1. antibiotics - 5ASA 2. systemic steroids - budesonide 3. MTX - AZA/6MP 4. TNF-antagonists 5. surgery
50
What is the 'top down' process of treating Crohn's disease?
1. combination therapy 2. steroids 3 surgery This is used when people have clinical features that suggest poor prognosis
51
What is involved in combination therapy to treat Crohn's disease?
Early introduction of thiopurines, methotrexate and anti-TNF
52
What is sulphasalazine?
It consists of sulphapyridine diazo bonded to 5-ASA (mesalamine)
53
What happens to sulphasalazine when it reaches the colon?
90% reaches the colon unchanged as the azo bond prevents proximal absorption Colonic bacteria split the molecule into 2 parts - allowing it to be active
54
What is sulphasalazine split into and which enzymes perform this?
1. 5-ASA 2. sulphapyridine This is performed by azo reductases
55
What is 5-ASA absorption like in the small bowel and colon?
1. rapid absorption in the proximal small bowel | 2. poor absorption in the colon (20%)
56
How are 5-ASAs administered?
They can be given orally or through rectal preparations These are foams, enemas and suppositories
57
How must 5-ASAs be stored and why?
They must be stabilised with anti-oxidants and protected from sunlight They are poorly soluble and unstable in suspensions
58
What happens to azathioprine when it is ingested?
It is converted to 6-mercaptopurine This is then converted to 6-thioguanine
59
What happens to 6-thioguanine once it is formed?
It is broken down into thioinosinic acid and thioguanylic acid These are then conjugated with ribose
60
What happens once thioinosininc acid and thioguanylic acid are conjugated with ribose?
They are incorporated into DNA and halt replication This inhibits purine biosynthesis
61
What happens if thioinosininc acid and thioguanylic acid are phosphorylated to triphosphate forms?
They block Rac1 This increases apoptosis of mononuclear cells
62
What is the overall action of azathioprine?
It increases apoptosis of inflammatory cells This reduces cell turnover and reduces T-cell mediated inflammation
63
What is the main role of methotrexate?
It inhibits folate metabolism
64
How does methotrexate reduce the inflammatory response?
It leads to changes in interleukins, which reduce the inflammatory response 1. IL-1 receptor blockade 2. Increased IL-2 production 3. Decreased IL-6 and IL-8 production 4. Impaired neutrophil chemotaxis
65
How do biologics work?
They are monoclonal antibodies that have a high affinity for certain molecules within the inflammatory cascade They bind to them and make them inactive
66
How do anti-TNF biologics work?
They bind to TNF-a This prevents it from binding to TNFR1/TNFR2
67
What are the main anti-TNF biologics?
Infliximab and adalimumab These lead to rapid mucosal healing
68
When are patients with IBD operated on in an emergency situation?
1. bowel perforation 2. bowel obstruction 3. toxic dilatation 4. severe bleeding 5. abscess
69
Why may a patient with IBD be operated on with an elective (planned) surgery?
1. cancer or pre-cancerous changes 2. failed medical treatments 3. the patient's choice
70
What is involved in a proctocolectomy with ileostomy?
Removal of the colon, rectum and anus The end of the small bowel is brought out to the surface of the abdomen as a stoma
71
What happens to the small bowel content after a procotocolectomy?
It passes into the stoma bag It is very liquid as it has not passed through the colon
72
What is involved in creating an ileal pouch following closure of loop ileostomy?
1. a neorectum is created using the small bowel 2. small bowel brought into the pelvis, folded back on itself and sutured into the anus 3. the anal sphincters are still present
73
Why can an ileal pouch not be performed in Crohn's disease?
Crohn's may return and affect the pouch
74
When is Ileocecal resection performed?
When Crohn's disease affects the terminal ileum The terminal ileum and the caecum are removed and the SI is joined to the colon
75
What is involved in colectomy with ileo-rectal anastomosis?
The colon is removed and the small intestine is joined to the rectum It is performed when Crohn's disease affects the colon
76
What are the benefits of laparoscopic (keyhole) operations?
1. less pain after operation 2. smaller scars 3. faster recovery 4. reduced risk of wound infection/hernia 5. shorter stay in hospital

BS - GI CLINICAL (4 decks)

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