7.2 Inflammatory bowel disease Flashcards
What defines IBD
A group of related conditions characterized by idiopathic inflammation of GIT
Conditions that cause macroscopic inflammation.
What are the 2 main non-specific IBDs?
What part of the GIT do they normally affect?
1) Ulcerative Colitis: only large bowel
2) Crohns Disease: small and or large bowel
Give 4 other causes of Colitis
- Drugs esp NSAIDs
- Ischaemic colitis
- Radiation colitis
- Diverticular colitis
- Microscopic colitis
- Collagenous colitis
- Infectious colitis
What are the 3 mains causes of IBD
1) Genetic susceptibility
2) Immune dysregulation
3) Environmental trigger
Give 4 triggers of IBD
Antibiotics Diet Acute Infections NSAIDs Smoking Stress
What is Crohn’s disease?
Chronic relapsing and remitting inflammatory disease of the digestive tract
What are the characteristics of Crohn’s disease
- Asymmetric
- Transmural involvement of the bowel wall
- Chronic Inflammatory process with non-caseating granulomas
Where are granulomatous infections seen in Crohn’s most commonly located
Frequently affects terminal ileum (but can affect any part of the GI tract)
What are the 2 main histological features of Crohn’s
1) Large epitheloid granulomas
2) Multinucleated giant cells
Compare the association with autoimmune disease in Crohn’s vs UC
UC: strong association with autoimmune disease eg hashimoto’s thyroiditis, SLE
Crohns: weak association with autoimmune disease
Compare the association with autoantibody production in Crohn’s vs UC
(Humoral component)
UC: common associated with autoantibody production eg anticolon antibody, perinuclear antineutrophil cytoplasmic antibody (pANCA)
Crohn’s: rare association with autoantibody production
Compare the Mucosal infiltration in Crohn’s vs UC
cell-mediated component
UC: Non granulomatous and neutrophil prominent
Crohn’s: Granulomatous and T cells prominent
Compare the T-cell reactivity in Crohn’s vs UC
cell-mediated component
UC: Normal or decreased
Crohn’s: Increased
List the clinical features of Crohn’s
- Diarrohea (chronic or nocturnal)
- Abdominal pain
- Weight loss
- Fatigue
- Anorexia or fever
- Abdominal mass or tenderness
- Intestinal obstruction
- May present with acute onset abdominal pain
- May mimic appendicitis
What is Ulcerative colitis
Chronic inflammation of part or the whole of the mucosa of the large bowel, diffusely inflamed and may ulcerate
What are the characteristics of UC
- only effects the colon (usually starts in rectum and extends proximally)
- continuous inflammation– no skip lesions (symmetrical)
- Circumferential
- Uninterrupted pattern
What parts of the GI tract does UC affect
The colon, Inflammation effects only the mucosa and submucosa
What are the 3 types of pattern of distributions seen in UC
1) Proctitis (rectum)
2) Left sided colitis (extends from the rectum up the colon and stops at the splenic flexure)
3) Pancolitis (entire large intestine)
What is the aetiology is UC/ what is a potential theory?
aetiology is unclear
theory: autoimmune disease caused by an inflammatory response to normal colonic microflora
What are the 3 main histological features of UC
1) Intense inflammatory cell infiltrate of the lamina propria
2) Goblet cell depletion
3) Crypt abcesses
List 4 other types Inflammatory Bowel diseases?
1) Microscopic colitis
2) Diversion colitis
3) Diverticular colitis
4) Pouchitis
what is the link between non-smokers and UC?
What is another thing that reduces risk of UC?
x3 more common in NON smokers
Appendecctomy before age 20
List 4 clinical features of UC?
- Bloody diarrohea
- Urgency
- Tensemus
- Nocturnal defecation
- Crampy abdominal pain or ache in left iliac fossa
- Pre-defactation pain relieved by passing stools
Tensemus is a clinical feature of UC, what does this mean?
a continual or recurrent inclination to evacuate the bowels, caused by disorder of the rectum or other illness
List 4 UC clinical SIGNS?
- Pallor
- Dehydration
- Mouth ulcers
- Abdominal tenderness
List 4 conditions associated with UC?
- Erythema Nodosum
- Pyoderma gangrenosum
- Uveitis
- Arthritis
In brief sentences how would you compare Crohn’s vs UC
Crohns Disease (CD) is a condition of chronic inflammation potentially involving any location of the GIT from mouth to anus in a discontinuous manner.
Ulcerative Colitis (UC) is an inflammatory disorder that affects the rectum (in 90% pts) & extends proximally in continuity to affect a variable extent of the colon.
What are the 2 main early findings of Crohn’s disease
1) Aphthous ulcer
2) The presence of granulomas
What are 4 main late findings of Crohn’s disease
1) Linear ulcers
2) The classic cobble stoned appearance may arise
3) Transmural inflammation
4) Sinus tracts, and strictures
5) Fibrosis.
UC can be classified as specific and non-specific, what do these mean?
Non-specific -> seen with any acute inflammation
Specific -> suggest chronicity
Describe 3 things that would be seen in non-specific UC
1) The lamina propria becomes oedematous.
2) Inflammatory infiltrate of neutrophils
3) Neutrophils invade crypts, causing cryptitis & ultimately crypt abscesses.
Describe 3 things that would be seen in specific UC
1) Distorted crypt architecture
2) crypt atrophy
3) a chronic inflammatory infiltrate
What is Toxic megacolon?
List a complication of Toxic Megacolon and its prognosis?
TM is a serious side effect of IBD: transverse colon becomes extremely dilated (above 6cm) resulting in ineffective function and serious infection.
Complication: perforation and rupture which can lead to peritonitis (in the presence of steroids physical signs may be absent)
Prognosis: four to five percent mortality without perforation and about 20% with perforation
List in order the treatment plan for IBD patients
1) 5-ASAs eg. Mesalazine
2) Steroids (short term) and Azathioprine (long term)
3) Clylosporine/ Infliximab
4) Surgery
(then Probiotics, alternative therapies, antibiotics)
What is thumb printing and what does it indicate?
Radiological sign: thickening at regular intervals throughout lumen which appear like thumb prints
TMC Indicative of Crohn’s
What is the Fat Halo sign and what does it indicate?
CT scan: infiltration of the mucosal layer of the fat causing a halo around it
Indicative of Crohn’s
What is Mesalazine (also known as mesalamine) and what is its mode of action
- also known as 5-aminosalicylic acid (5-ASA) it is a derivative of salicylic acid
- more effective in UC than Crohns
- used for IBD maintenance
Mode of Action: mesalazine is thought to be an antioxidant that traps free radicals
List 4 side effects of Mesalazine
- renal impairment
- diarrhoea
- allergy
- hepatitis
- myopericarditis
What is the mode of action of steroids in use of IBD treatment?
What is its route of administration?
- Potent anti inflammatory actions via multiple inflammatory pathways
- used to obtain control in active disease (more effective than 5 ASA)
Route of administration: Oral / Topical / IV
List 4 side effects of Thiopurines
- Allergic ( fever, arthralgia, rash)
- Hepatoxic,
- Bone marrow toxicity
- long term …. malignancy
Need regular monitoring of bloods FBC / LFT
List 4 side effects of Thiopurines
- Allergy
- Hepatoxic
- Bone marrow toxicity
- long term …. malignancy
Need regular monitoring of bloods FBC / LFT
What is the mode of action of Methotrexate in use of IBD treatment?
When would you use it and at what dose?
Mode of action: inhibits dihydrofolate reductase hence cytotoxic BUT its anti inflammatory action is by inhibiting cytokine and eicosanoid synthesis.
Use: second line drug of azothioprine failes or is not tolerated.
Dose: Once weekly with folic acid
List 4 side effects of Methotrexate
Short term: nausea, diarrhoea
Long term : hepatoxicity, pneumonitis
Note: Very Teratogenic
What is the Mode of action of calcineurin inhibitors?
Give an example of one
How is it administered?
eg. Ciclosporin and Tacrolimus
Mode of action : inhibition of calcineurin which inhibits clonal expansion of T cell subsets
Administration : IV or oral
Only beneficial As a rescue therapy in severe UC (no effect in Crohn’s)
Give 4 side effects of calcineurin inhibitors
minor tremor paraesthesia hirutism major seizures if low cholesterol or magnesium renal
List 2 Biological Therapies that can be used in treatment of IBDs
1) Infliximab and Adalimumab
2) Etanercept
What is TNF-α
TNF-α is a chemical messenger (cytokine) and a key player in the inflammatory process involved in IBD.
What is the mode of action of Infliximab and Adalimumab?
Infliximab and Adalimumab are monoclonal antibodys targeting tumour necrosis factor α (TNF-α).
Infliximab works by binding to TNF-α and preventing it from binding to receptors involved in the inflammatory process
What is the mode of action Etanercept?
Etanercept is a recombinant human TNF receptor fusion protein
It inhibits the binding of TNF to its cell surface receptor
