Inflammatory bowel disease Flashcards
What are the two diagnoses that fall under the inflammatory bowel disease label?
Ulcerative colitis and Crohn’s disease.
What is the age range for IBD?
15-40
Describe the process of early gut inflammation.
Antigenic activation of innate immune cells (NK cells, mast cells neutrophils, macrophages, and dendritic cells).
Describe the processes behind the maintenance of the inflammatory response in the gut.
Maintained by the adaptive immune response. Abnormally activated CD4+ cells release pro-inflammatory mediators leading to chronic tissue damage.
What is the cause of inflammatory bowel disease?
Failure to maintain oral tolerance.
What are the genetic factors associated with IBD?
NOD2 (Crohn’s) - involved in intracellular processing of bacterial antigens.
IL-23R (Crohn’s and UC) - involved in regulation of Th-1 and Th-17 cell differentiation.
What is the largest independent risk factor for IBD.
Positive family history.
How does the distribution of UC differ from Crohn’s?
UC- Rectum and colon only
Crohn’s - GI tract, mouth and anus
How does the histology of UC differ from Crohn’s?
UC - mucosa/submucosa
Crohn’s - transmural
What impact does smoking have upon UC and Crohn’s?
UC - seems to improve?
Crohn’s - worsens
What surgical interventions may be used in UC and Crohn’s?
UC - pan-protocolectomy +/- pouch
Crohn’s - depends on distribution
What features present in Crohn’s are not present in UC?
Reccurance after surgery, peri-anal diseas, fistulae and abcesses.
What are the possible extraintestinal manifestations of IBD?
Arthritis, sacroiliitis, ankylosing spondylitis, osteoporosis
Various dermatologic.
Thrombotic events, vasculitis.
Uveitis, scleritis, episcleritis.
Various renal, pancreatic and hepatobiliary.
What blood tests might you do for inflammatory bowel disease?
CRP, calprotectin and other markers of inflammation.
What radiology investigations might you do for IBD?
Barium series, CT, MRI.
What are the different types of ulcerative colitis?
Proctitis, left-sided colitis and pan-colitis.
What are the possible symptoms of UC?
Diarrhoea with blood and mucous, urgency, weight loss, abdo pain, cramps and nocturnal symptoms.
What are the possible signs of UC?
Tender abdomen, tachycardia, pyrexial and extra-intestinal manifestitions.
What is the initiating stimulus in IBD?
Commensal gut flora - patient studies demonstrate hypersensitivity to own gut bacterial antigens.
Which immunomodulatory drug would be used to treat UC but not Crohn’s.
Ciclosporin
What other immunomodulatory drugs may be used in IBD?
Methotrexate and azathioprine.
For which condition are the mesalazines better?
UC
What biologics may be used in the treatment of IBD?
Anti-TNF and vedolizumab.
What is the mechanism of action for methotrexate?
Inhibits folate metabolism. Cytotoxic effects via DHFR inhibition. Also anti-inflammatory effect. Leads to IL-1 receptor blockade, increase IL-2, decrease IL-6 and 8 and impaired neutrophil chemotaxis.
Under what circumstances would you perform emergency surgery for IBD?
Bowel perforation, bowel obstruction, toxic dilatation, severe bleeding and abcess.
Under what circumstances would you perform elective surgery for IBD?
Cancer (pre-cancer), failed medical treatment and choice.
What is a proctocolectomy with ileostomy?
Removal of rectum, colon and anus with ileostomy.
How might a loop ileostomy be closed?
Creation of an ileal J-pouch and anal anastamosis.
What is an ileocaecal resection?
Part of the bowel is removed and the healthy parts anastamosed together.
What is a colectomy with ileorectal anastamosis?
Removal of the colon, anastamosis of ileum to rectum.
What are other potential forms of therapy for IBD.
Inhibitors of inductive cytokines, cytokines to induce Tregs, vectors, attenuated helminths, faecal transplantation.
What genetically modified probiotic organism may be used in the treament of IBD and what are its limitations?
Lactococcus lactis secreting IL-10. IL-10 production cannot be regulated and L.lactis is non-colonising.
How does worm therapy work?
Trichuris suis can colonise people but not replicate. May work by stimulation of Tregs. 80% response and 72% remission.
