7.2: IBD

Question 1

What are the two main types of IBD? Which is more common?

Name four other types of IBD with other causes

Answer 1

1. Ulcerative colitis - slightly more common
2. Crohn’s disease
   But there are other causes of colitis such as drugs, ischemic colitis, radiation colitis (side effect from radiotherapy), infectious colitis (e.g; Shigella, etc)

Question 2

Describe any significant epidemiology findings that put certain individuals at risk for IBD in the following categories; race, age, geography, smoking and genetics

Answer 2

1. Race; 3X more likely if your white in the US
2. Age; peaks between 20-30 and 50-60
3. Geography; common in developed countries
4. Smoking; 4X more likely for crohn’s
5. Genetics; HLA B27 is the antigen associated with ulcerative colitis

Question 3

What is one unique unexplainable thing that lessens your chances of getting IBD? Interestingly, what condition might crohn’s mimic?

Answer 3

No appendix! But the clinical presentation of crohn’s may mimic appendicitis

Question 4

What are the three main causes of IBD?

Answer 4

1. Environmental triggers
2. Genetic susceptibility
3. Immune dysregulation

Question 5

Name 5 triggers for IBD

Answer 5

1. Stress; causes an altered autoimmune response
2. Smoking
3. Diet
4. Drugs; Antibiotics and NSAIDs
5. Acute infections

Question 6

Define Crohn’s Disease

Answer 6

Chronic relapsing and remitting inflammatory disease of the digestive tract

Question 7

Name (and describe if necessary) 4 characteristics of Crohn’s

Answer 7

1. Focal; targeted area of the bowel
2. Asymmetrical; no pattern, sporadic throughout the bowel
3. Transmural involvement of the bowel wall
4. Chronic inflammatory process with non-caseating granulomas (no necrotic material)

Question 8

Which part of the GI tract is usually affected by granulomatous inflammation in Crohn’s?

Answer 8

Frequently affects the terminal ileum but can affect any part of the GI tract

Question 9

Which absorption process will be hindered in a patient with classic crohn’s?

Answer 9

Vit B12 absorption, as granulomatous inflammation in crohn’s commonly affects the terminal ileum

Question 10

Name four things you might see macroscopically in the GI tract in Crohn’s disease

Answer 10

1. Cobblestoning
2. Bleeding
3. Fistulas (links between bowel and outside world), and can cause abscesses and infection
4. Ulceration

Question 11

Name two major histological changes would you notice in Crohn’s disease

Answer 11

1. Large epitheloid granulomas

2. Multinucleated giant cells

Question 12

Describe the association with autoimmune disease and autoantibody production for Crohn’s and Ulcerative colitis

Answer 12

Crohn’s; weak association with autoimmune diseases and rarely associated with autoantibody production (like an anti colon antibody, etc)

Ulcerative colitis: strong association with autoimmune diseases and commonly associated with autoantibody production

Question 13

Describe the T cell reactivity, type of granuloma (if there is one) and prominent cell type in Ulcerative colitis and Çrohn’s

Answer 13

Crohn’s is granulomatous T cell prominent with increased T cell reactivity

Ulcerative colitis is non granulomatous and is neutrophil prominent, with normal or decreased levels of T cell reactivity

Question 14

Name 6 possible clinical features of Crohn’s disease

Answer 14

1. Diarrhea - chronic or nocturnal
2. Abdominal pain (may also present with acute onset abdominal pain), may be around L or R iliac fossa
3. Weight loss
4. Fatigue; could be caused by anorexia (B12 deficient) or fever
5. Abdominal mass or tenderness
6. Intestinal obstruction

Question 15

Define ulcerative colitis

Answer 15

Part or the whole of the mucosa of the large bowel is inflamed and may be ulcerated

Question 16

Which parts of the bowel tend to be affected in ulcerative colitis and what is the common spreading pattern? Name 4 other characteristics of ulcerative colitis.

Answer 16

May affect parts of the colon or its entire mucosal surface
Usually starts in rectum and extends proximally
1. Symmetrical; both sides of the bowel
2. Circumferential; goes around the bowel
3. Uninterrupted pattern; No skip lesions (no cobblestone appearance)
4. Inflammation effects only the mucosa and submucosa

Question 17

Name the three patterns of distribution for ulcerative colitis

Answer 17

1. Proctitis; affects the rectum/last part
2. L sided colitis; L sided iliac fossa pain, affects up the descending colon
3. Pancolitis; affects the whole colon

Question 18

What is the cause of ulcerative colitis? Is there genetic influence in comparison to crohn’s?

Answer 18

Unknown cause, but a theory is that its an autoimmune disease caused by an inflammatory response to normal colonic microflora. There is genetic influence but less strong than crohn’s

Question 19

Describe three major histological changes you might notice in Ulcerative colitis

Answer 19

1. Intense inflammatory cell infiltrate of lamina propria
2. Goblet cell depletion
3. Crypt abscesses; dead necrotic material in the middle that may cause infection

Question 20

What are pseudopolyps and why are they associated with ulcers?

Answer 20

Pseudopolyps are projecting masses of scar tissue that develop from granulation tissue, the breakdown of layers causes ulceration

Question 21

Is ulcerative colitis more common in smokers?

Answer 21

NO it’s 3X more common in non smokers

Question 22

Name 6 potential clinical features of ulcerative colitis

*Hint; characteristics of stools and pain

Answer 22

Depends on the severity and extent of the condition

1. Bloody diarrhea; due to mucosal breakdown
2. Urgency
3. Tensemus; recurrent inclination to evacuate bowels
4. Nocturnal defecation
5. Crampy abdominal pain or ache in L iliac fossa (not acute like crohn’s can be)
6. Pre-defecation pain relieved by passing stools

Question 23

Name four other associated conditions with UC

Answer 23

1. Erythema Nodosum
2. Pyoderma gangrenosum
3. Uveitis; inflammation of eye
4. Arthritis

Question 24

Name 5 clinical signs of UC

Answer 24

1. Pallor
2. Dehydration; not resorting water in the large bowel properly
3. Mouth ulcers; diff pathology to crohn’s
4. Abdominal tenderness
5. Constipation; common in proctitis

Question 25

Name two ‘early findings’ and five ‘late findings’ for CD

Answer 25

Early findings: 1. Aphthous ulcer; ulcer that forms on the mucous membrane 2. Presence of granulomas Late findings: 1. Linear ulcers 2. Cobble stone appearance 3. Transmural inflammation 4. Fistulas and strictures 5. Fibrosis

Question 26

What might you see in ‘non specific’ (meaning these things may be found with any acute inflammation) and ‘specific’ (suggesting chronicity) UC?

Answer 26

Non specific; lamina propria becomes oedematous, neutrophils infiltrate invading crypts; causing cryptitis and crypt abscesses Specific; distorted crypt structure, crypt atrophy and chronic inflammatory infiltrate

Question 27

Which IBD would you suspect if there was gross bright red bleeding?

Answer 27

UC, especially if it’s bright red which indicates the blood hasn’t been digested and the problem is distal

Question 28

What is Toxic Megacolon and how can it be seen?

Answer 28

Serious side effect of IBD, the colon (typically transverse colon) becomes dilated to >6cm. Within is a collection of infection and it may rupture which causes more infection and peritonitis. Can be seen on an abdominal X ray and a perforation can be seen easily on a CT scan

Question 29

How does perforation of a toxic megacolon influence prognosis? When would you see absent physical signs?

Answer 29

Mortality changes from 4-5% (without perforation) to 20% with perforation. Physical signs may be absent in the presence of steroids

Question 30

What might you notice on an X ray and a CT scan with CD?

Answer 30

X ray: Thumb printing; illustrates the skip lesions CT: Fat halo sign; infiltration of fat into the mucosal layer that causes a ‘halo’ around it

Question 31

What drugs might you offer as part of IBD treatment?

Answer 31

Mesalazine, steroids, thiopurines like azothioprine (neurodrugs), methotrexate, calcineurin inhibitors

Question 32

Describe the mode of action for mesalazine, how is it used and which major IBD is it more effective on?

Answer 32

Thought to be an antioxidant that traps free radicals (byproducts of damage to the mucosal cells) and is used for maintenance - though high doses may help achieve control More effective for UC>CD

Question 33

Name four severe side effects of Mesalazine

Answer 33

1. Renal impairment 2. Diarrhea 3. Hepatitis 3. Myopericarditis

Question 34

Describe the mode of action for steroids in IBD. Name three potential routes of administration and six severe side effects

Answer 34

Steroids have potent anti inflammatory actions and are used to obtain control over the active disease, they are not used for maintenance. They can be administered orally, topically or IV Severe side effects include; weight gain, hypertension, glucose impairment, osteoporosis, adrenal suppression and mood disturbance

Question 35

Describe the mode of action for thiopurines, what are they used with and how is the dose determined? What must be monitored alongside a prescription and why?

Answer 35

They induce T cell apoptosis (can be useful in CD) alongside steroids, the dose is weight dependent. They also require regular monitoring of FBC and LVT as long term use is associated with bone marrow toxicity, hepatoxicity and malignancies.

Question 36

Describe the mode of action for methotrexate, when is it used and what is the dose? Name two short-term and two long-term side effects and a side effect important in expecting mothers.

Answer 36

It has anti-inflammatory action by inhibiting cytokines and eicosanoid synthesis (also inhibits dihydrofolate reductase and is cytotoxic). It’s used as a second line drug after azothioprine if it fails and it’s dose is once a week with folic acid Short term side effects: nausea, diarrhea Long term side effects: hepatoxicity, pneumonitis Very teratogenic

Question 37

How do calcineurin inhibitors work?

Answer 37

They inhibit calcineurin which inhibits clonal expansion of T cell subsets

Question 38

Name three biological therapies for IBD and briefly describe how they work

Answer 38

Since TNF-a is a cytokines and key player in the inflammatory process involved in IBD... 1. Infliximab and adalimumab are antibodies that target TNF-a 2. Etanercept is a recombinant human TNF receptor fusion protein which inhibits the binding of TNF to its cell surface receptor

Question 39

What is the last resort medical treatment for IBD? Name four signs that this intervention is needed

Answer 39

Surgery, if the patient is defecating >8 times a day despite medication, have worsening temperatures, toxic megacolon beginning, low albumin and Hb

Question 40

Name two common surgical interventions for UC

Answer 40

1. Colectomy | 2. Ileostomy

Question 41

What is the danger of surgical intervention in Crohn’s disease patients?

Answer 41

Since the inflammation is discontinuous there is risk of the disease reappearing in another part of the GI tract and the fistulas may return

Question 42

What is one intervention that can be done for fistulas?

Answer 42

Seton stitch: guided through the fistula tract and tied exteriorly, it compresses and maintains the suture placement in the tract