Inflammatory Bowel Disease Flashcards
Where does Crohn’s Disease affect, ,what causes it and how does it fluctuate?
- Anywhere on the GI tract
- Cause is unknown
- Exacerbations and remission
How does the inflammation in Crohn’s differ from UC and how is it caused?
- Crohn’s:
Transmural inflammation (throughout wall of GI tract)
Caused by dense infiltration of lymphocytes and macrophages - Ulcerative Colitis:
Inflammation of mucosal layer ONLY
Caused by an infiltration of inflammatory cells into mucosa
What are the differences in consequences of inflammation in Crohn’s vs. UC?
Crohn’s:
- Fissuring ulceration (eating away at wall of tract leads to fistulae)
- Submucosal fibrosis (scar tissue formation between epithelial + smooth muscle leading to strictures)
UC:
- Loss of goblet cells (inflammation affects mucosal layer)
- Presence of ulcerations
What are the symptoms of Crohn’s?
- Diarrhoea
- Pain
- Narrowing of the gut lumen leading to strictures (narrowed lumen) and bowel obstruction
- Abscess formation
- Fistulization to skin and internal organs
How do strictures form and how do they affect you?
- Inflammation (from infiltration of lymphocytes/macrophages) leads to scar tissue formation
- This leads to narrowing of the lumen and then obstruction
- Risk of rupture as pressure builds at narrow lumen/obstruction
- Resulting in pain/cramp/bloating
- Scar tissue = poor absorption of food/drug
How do fistulae form and where are they found?
- Via ulcers; inflammation leads to ulcers
- These develop into tunnelst = fistulae
- Go between areas of GIT, between organs (to bladder etc) or to skin (anal fistula)
What are the consequences of Crohn’s?
- Weight loss
- Macronutrient/micronutrient deficiency (when inflamed/exacerbated)
- Fatigue
What are the differences in how nutrition is affected between Crohn’s and UC?
Crohn’s:
- Protein-energy malnutrition in 20-80% of patients
- Weight loss from macro/micronutrient deficiency
UC:
- Less severe nutritional consequences (inflammation of the colon only : none observed aside from in severe diarrhoea with electrolyte/fluid loss, and GI pain can affect appetite)
What are the symptoms of ulcerative colitis?
- Severe diarrhoea (electrolyte/fluid loss)
- Blood loss (via ulcers; lowers blood pressure)
- Loss of peristaltic function leading to rigid colonic tube > potentially leading to toxic megacolon in severe cases
What is toxic megacolon?
Distension of the colon resulting in perforation and systemic toxicity in the form of sepsis; colonic bacteria enter bloodstream
How does taking loperamide affect UC?
Patients unwittingly take loperamide to stop severe diarrhoea but ends up contributing to the loss of peristaltic function (and potentially leading to toxic megacolon)
Where can extra-intestinal inflammation occur and for which IBD?
- In joints/eyes/skin/mouth/liver
- In Crohn’s and IBD
(systemic disease)
What is the mode of action of 5-aminosalicylate (mesalazine) and what does it treat?
- It inhibits leukotriene & prostanoid synthesis, scavenges free radicals and decreases neutrophil chemotaxis (movement/activity from chemical stimulus - changes in gene transcription of PPAR(gamma) receptor)
- Sulfasalazine is metabolised to mesalazine (requires colonic bacteria)
- Effects observed in UC/questionable use in Crohn’s
What issues with absorption could arise from sulfasalazine to treat UC?
Sulfasalazine is a pro-drug; required to be metabolised by colonic bacteria in to the active drug mesalazine; may have insufficient time for metabolism w/severe diarrhoea
How are steroids used in IBD?
For their anti-inflammatory and immunosuppressive effect:
- Corticosteroids
E.g. budesonide; poorly absorbed thus far fewer systemic side effects
-Used to induce remission (particularly in severe disease)
-Enemas used for more distal or rectal inflammation e.g. Predfoam
What immunosuppressants are used in IBD and how do they work?
Azathioprine (1st choice; converted to active mercaptopurine) and methotrexate; inhibit purine synthesis and thus DNA, reducing inflammatory cell proliferation.
Cyclosporine (used when no response to above/steroid-sparing); inhibiting IL-2 (interleukin 2) induced gene expression
What are the potential dangers with using azathioprine?
- Azathioprine converted to active form mercaptopurine which is then metabolised via multiple pathways incl. TPMT (thiopurine methyltransferase; inactivation) and HGPRT (therapeutic)
- Some patients have little to no TPMT activity; thus mercaptopurine all metabolised by HGPRT which normally gives rise to desired immunosuppression via cytotoxic nucleotide analogues
- But w/o TPMT to ‘deal’ with some mercaptopurine too there’s too much of the toxic analogue; bone marrow toxicity
DO TPMT TEST TO DETERMINE POSSIBLE TOXICITY
What is the mode of action for infliximab (infusion) and adlimumab (injection) and what do they treat?
- They neutralise the inflammatory cytokine TNF-a(lpha)
(however associated w/risk of TB) - Monocolonal antibodies for severe, active Crohn’s
How are elemental feeds beneficial for Crohn’s?
They can induce remission; ingesting basic amino acids/lipids (elements) that don’t have to be digested.
Why would small bowel removal occur in Crohn’s and what are the consequences?
- V shitty stricture-y/narrow/scarred part
- Resulting in a shortened bowel, meaning reduced absorption of food/drug
- Requiring nutritional support
- Parenteral nutrition may be required generally to prevent undernutrition
How are probiotics beneficial in UC?
UC potentially caused by pathogenic colonic bacteria; add ‘friendly bacteria’ such as Yakult
What is the treatment tree of Crohn’s for remission?
1.) Monotherapy - Conventional steroid (prednisolone etc)
[alternative = budesonide/5-ASA)
2.) Add-on therapy:
First line: Azathioprine or mercaptopurine
Second line: Methotrexate (if patient has low TPMP enzyme)
3.) Severe active Crohn’s:
Infliximab or adlimumabb.
What counselling points are there with oral steroids?
- Best taken as single dose in morning after food
- Avoid contact with people who have shingles/chickenpox/measles
- Carry steroid treatment card if taking oral corticosteroids for
