Crohn's Disease

Question 1

What is Crohns disease?

Answer 1

A chronic inflammatory bowel disease that affects the gastrointestinal tract. It can cause inflammation throughout the digestive system, but most often affects the large intestine or the final section of the small intestine.

Question 2

Pathophysiology of Crohn’s

Answer 2

1. Initial trigger caused by enviromental, genetic, dietery factors, or imparied barrier function
2. Activates the release of macrophages and T-cells
3. Release of Cytokines: TNFa , Interferon-Gamma, IL-1, IL-6
4. This results in further immune activation and increased tissue damage
5. This all leads to chronic intestinal inflammation (IBD).
6. Build up of macrophages causes granulomas to form (inflamation)

Question 3

disease characteristics of Crohn’s

Answer 3

1. Can affect any part of GI tract (Mouth->Rectum)
2. Skip lesions
3. Most common location: ileocaecal area or small intestine
4. Transmural inflamation: inflammation of all layers of the bowel wall.
5. Can result in fissures, cobble stone effect, thickened wall, fat wrapping

Question 4

Disease characteristics of Ulcerative Colitis

Answer 4

1. Affects Colon only
2. Continuous Lesions
3. always starts at the rectum>bloody stool - LLQ pain
4. superficial inflamation - only inflammation of mucousa
5. incomplete evacuation or tenesmus

Question 5

Signs and symptoms of Chrons and Ulcerative Colitis

Answer 5

See table

Question 6

Causes of Crohn’s disease

Answer 6

1. Gentic
   * Family history
   * gene mutation
2. Enviromental
   * northern european/american
   * smoking

Question 7

Pathophysiology of Ulcerative Colitis

Answer 7

1. T-cells release TNFa propegating inflamation. IL4,IL5 released propegating inflamation
   2.

Question 8

Causes of Ulcerative Colitis

Answer 8

1. Gentic
   * Family history
   * gene mutation
2. Enviromental
   * northern european/american
   * non-smoking/ex-smokers

Question 9

Complications with Crohn’s:
Malabsorption

Answer 9

1. Malabsorption - Ileum primary point of absoprtion of fat, therefore if effected decreased absorption of fat soluble vitamins: ADEK,B12
   * weight loss
   * macrocitic anaemia

Question 10

Complications with Crohn’s:
Fistulas, abscess

Answer 10

1. Erosion of the bowel wall can create pathways into other organs allowing entry of bacteria, faeces, air
   * increased infections (UTI)
2. Peri-anal abscess

Question 11

Complications with Crohn’s:
Strictures

Answer 11

1. Inflamation narrows the Gi tract and can cause obstruction into intestinal material moving through
   * cramps, abdominal pain

Question 12

Complications with Ulcerative Colitis:
Colitis/Megacolon

Answer 12

1. increased:
   * pain
   * fever
   * WCC
2. Reduced absorption
3. increased bloody stool
4. increased risk of bowel perforation
5. toxic megacolon

Question 13

Complications with Ulcerative Colitis: Cancer

Answer 13

1. Increased risk of colorectal cancer due to chronic inflamation

Question 14

Aminosalicylates in IBD

Answer 14

Mesalazine (5-ASA)
* First line for mild-moderate UC
* Maintenance of remission UC
* Topical anti-inflamatory effect on colonic epeithelial cells (bowel mucousa)
* Oral must be GR othwerwise absorbed before site of action
* Rectal (suppository, foam, enema)
* Renal excretion (potential dehydration, nephrotoxic)
* Oral preperations are not interchangable due to formulated release. ie; pH, time
Side effects: Diarrhoea, nausea, headache, arthralgia (joint pain)
Blood disorders: Arganulocytosis, thrombocytopeina

Question 15

Corticosteroids in IBD

Answer 15

Budesonide, Prednisolone, Methylprednisolone
* Induces remission in both Crohn’s and UC
* Not used for maintenance
* Potent anti-inflamatory which inhibits several anti-inflamatory pathways: interlukin transcription, reduction of pro-inflamatory mediators: histamine, prostaglandins
* Budesonide is less effective, but less side effects
* Oral, rectal, IV
* Must be tapered off

• short term side effects: moon facies (puffy face), sleep/mood disturbance, dyspepsia, weight gain, increased blood gluclose, increased blood pressure
• Long term side effects: osteoporosis, myopathy, infections, risk of T2DM
• Abrupt withdrawl of long-term treatment: accute adrenal insufficiency, disease flare

Question 16

Thiopurines in IBD

Answer 16

Mercatopurine, Azathioprine
* Pro-drugs of 6-MP)
* incorporated into replicating DNA and RNA - blocking the synthesis of puriness and blocking growth of fast growing cells, including immunce cells, immunosuppressant
* Takes 2-6months to take effect
* Maintenance of Crohn’s
* Step up therapy of UC
*

• Side effects: flu-like symptoms, nausea, hepatotoxicity, pancreatitis, bone marrow supression
• Frequent FBC and LFT required
• Increased risk of skin cancers
• TPMT activity level must be assesed prior to starting therapy

Question 16

Biologics in IBD

Answer 16

TNFa inhibtors:
* Infliximab, Adalimumab, Golimumab
* Bind to TNFa and prevent further immune action

Integrin blocker:
* Vedolizumab
* Prevents entry of certain WBC into bowel mucosa

IL-12 IL-23 blocker:
* Ustekienemab
* Prevents action of cytokines IL-12, IL-23 on immunce cells
* Requires 1st dose in hospital

Adverse effects: risk of hypersensitivty, risk of infection, flu symptoms, nausea, diarrhoea

Question 16

Mehthotrexate in IBD

Answer 16

Methotrexate
* Inhibits dihydrofolate reductase, preventing DNA/RNA/Protein synthesis and growth of fast growing cells. Accumulation of some purine precursors also has anti-inflammatory effect
* Induces remission and prevents relapse in Crohn’s where Azathioprine is innefective/not tolerated.
* No proven beneift in UC
* GI side effects limited with folic acid 5mg
* ONCE weekly.

Side effects: nausea, fatigue, vomitting, diarrhoea, stomatitis, Hepatotoxicity, Penuemonia, bone marrow supression
Renal excretion: avoid nephrotoxins if possible
avoid other medications involved in bone marrow supression
frequent FBC and LFTs required

Question 17

Treatment approach order IBD

Answer 17

See table.