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BS - GI CLINICAL > Inflammatory Bowel Disease > Flashcards

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
Q

What are the 5 symptoms of ulcerative colitis?

A
  1. diarrhoea with mucous + blood
  2. urgency
  3. weight loss
  4. abdominal pain/cramps
  5. nocturnal symptoms
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26
Q

What are the clinical signs of ulcerative colitis?

A
  1. tender abdomen
  2. tachycardia
  3. pyrexia (fever)
  4. extra-intestinal manifestations
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27
Q

How can an abnormal colon be seen on an X-ray?

What is the fear associated with this?

A

The colon is distended

Haustral folds are not visible - it looks smooth

When the colon is distended, there is fear of perforation

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28
Q

What types of features may be seen on a endoscopy for ulcerative colitis?

A
  1. granular mucosa
  2. spontaneous bleeding
  3. deep ulcers
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29
Q

Where is inflammation found in ulcerative colitis?

What may develop as a result of inflammation?

A

Inflammation is confined to the colon

Inflammation is continuous and affects only the mucosa and submucosa

Pseudo-polyps may develop

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30
Q

What may a barium enema show in an ulcerative colitis patient?

A
  1. mucosal thickening
  2. areas of mucosal loss
  3. visible ulcers

(particularly in the descending colon where they have a typical undercut edge)

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31
Q

What is seen in an endoscopy for Crohn’s disease?

A
  1. ileal ulcers
  2. erythema
  3. inflammation
32
Q

What is erythema?

What is is caused by?

A

Redness of the skin or mucous membranes

Caused by hyperaemia - increased blood flow - in superficial capillaries

33
Q

Which parts of the colon are affected by Crohn’s disease?

A

It can affect any part of the GI tract, but commonly the colon and ileum

34
Q

What are the typical features of Crohn’s disease?

A
  1. discontinuous inflammation
  2. transmural
  3. with granulomas
35
Q

Why does Crohn’s disease show “discontinuous inflammation”?

A

There are patches of normal bowel between the inflamed areas

36
Q

How are IBDs mediated?

A

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
Q

What is the initiating stimulus in IBD?

Why?

A

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
Q

What is the balance involved in tolerance?

A

Tolerance involves a balance between T helper cells (Th1, Th2, Th17) and T regulatory cells

39
Q

What happens if the balance between T-helper cells and T-regulatory cells is disrupted?

A

More T-regulatory leads to opportunistic infection

More T-helper leads to inflammation and tissue damage

40
Q

Why does having too many T-regulatory cells lead to opportunistic infection?

A

There is a risk of suppressing the immune system

41
Q

What are the main drugs used to treat IBD?

What are the problems with them?

A
  1. steroids - cannot be used long-term

2. mesalazines - better for treating UC

42
Q

What are the immunomodulator drugs used to treat IBD?

A
  1. azathioprine - used for Crohn’s and UC
  2. methotrexate - used for both but mainly UC
  3. ciclosporin - only used for severe UC
43
Q

What biologics are used to treat IBD?

A
  1. Anti-TNF is used for both, but is better for UC

2. Vedolizumab is used for both

44
Q

When are steroids used in IBD treatment and why?

A

They bring inflammation under control quickly and early-on

Their side effects mean they are not suitable for long-term use

45
Q

What are steroids then replaced by?

A

Mesalazines or immunomodulators

Mesalazines are only really used in UC

46
Q

What are biologics?

A

Drugs that target certain cytokines and elements of the inflammatory cascade to prevent inflammation

47
Q

What are the main complications of Crohn’s disease?

How are they treated?

A
  1. abscess
  2. fistula
  3. perforation
  4. stricture
  5. cancer

They cannot be treated through medical intervention, so must be treated surgically

48
Q

What can dampening down inflammation do in Crohn’s disease?

What happens if inflammation persists?

A

Dampening down inflammation tends to relieve strictures

If inflammation persists, scar tissue develops that must be removed surgically

49
Q

What are the steps involved in ‘step up’ treatment of Crohn’s disease?

A
  1. antibiotics - 5ASA
  2. systemic steroids - budesonide
  3. MTX - AZA/6MP
  4. TNF-antagonists
  5. surgery
50
Q

What is the ‘top down’ process of treating Crohn’s disease?

A
  1. combination therapy
  2. steroids

3 surgery

This is used when people have clinical features that suggest poor prognosis

51
Q

What is involved in combination therapy to treat Crohn’s disease?

A

Early introduction of thiopurines, methotrexate and anti-TNF

52
Q

What is sulphasalazine?

A

It consists of sulphapyridine diazo bonded to 5-ASA (mesalamine)

53
Q

What happens to sulphasalazine when it reaches the colon?

A

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
Q

What is sulphasalazine split into and which enzymes perform this?

A
  1. 5-ASA
  2. sulphapyridine

This is performed by azo reductases

55
Q

What is 5-ASA absorption like in the small bowel and colon?

A
  1. rapid absorption in the proximal small bowel

2. poor absorption in the colon (20%)

56
Q

How are 5-ASAs administered?

A

They can be given orally or through rectal preparations

These are foams, enemas and suppositories

57
Q

How must 5-ASAs be stored and why?

A

They must be stabilised with anti-oxidants and protected from sunlight

They are poorly soluble and unstable in suspensions

58
Q

What happens to azathioprine when it is ingested?

A

It is converted to 6-mercaptopurine

This is then converted to 6-thioguanine

59
Q

What happens to 6-thioguanine once it is formed?

A

It is broken down into thioinosinic acid and thioguanylic acid

These are then conjugated with ribose

60
Q

What happens once thioinosininc acid and thioguanylic acid are conjugated with ribose?

A

They are incorporated into DNA and halt replication

This inhibits purine biosynthesis

61
Q

What happens if thioinosininc acid and thioguanylic acid are phosphorylated to triphosphate forms?

A

They block Rac1

This increases apoptosis of mononuclear cells

62
Q

What is the overall action of azathioprine?

A

It increases apoptosis of inflammatory cells

This reduces cell turnover and reduces T-cell mediated inflammation

63
Q

What is the main role of methotrexate?

A

It inhibits folate metabolism

64
Q

How does methotrexate reduce the inflammatory response?

A

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
Q

How do biologics work?

A

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
Q

How do anti-TNF biologics work?

A

They bind to TNF-a

This prevents it from binding to TNFR1/TNFR2

67
Q

What are the main anti-TNF biologics?

A

Infliximab and adalimumab

These lead to rapid mucosal healing

68
Q

When are patients with IBD operated on in an emergency situation?

A
  1. bowel perforation
  2. bowel obstruction
  3. toxic dilatation
  4. severe bleeding
  5. abscess
69
Q

Why may a patient with IBD be operated on with an elective (planned) surgery?

A
  1. cancer or pre-cancerous changes
  2. failed medical treatments
  3. the patient’s choice
70
Q

What is involved in a proctocolectomy with ileostomy?

A

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
Q

What happens to the small bowel content after a procotocolectomy?

A

It passes into the stoma bag

It is very liquid as it has not passed through the colon

72
Q

What is involved in creating an ileal pouch following closure of loop ileostomy?

A
  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
Q

Why can an ileal pouch not be performed in Crohn’s disease?

A

Crohn’s may return and affect the pouch

74
Q

When is Ileocecal resection performed?

A

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
Q

What is involved in colectomy with ileo-rectal anastomosis?

A

The colon is removed and the small intestine is joined to the rectum

It is performed when Crohn’s disease affects the colon

76
Q

What are the benefits of laparoscopic (keyhole) operations?

A
  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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