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Ulcerative Colitis. Which of the following would not be associated with UC . Toxic megacolon Granulomas Pseudopolyps Primary sclerosing cholangitis. Pathogenesis of IBD. Genetic susceptibility Failure of immune regulation Triggering by microbial flora.
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Which of the following would not be associated with UC • Toxic megacolon • Granulomas • Pseudopolyps • Primary sclerosing cholangitis
Pathogenesis of IBD • Genetic susceptibility • Failure of immune regulation • Triggering by microbial flora
Epidemiology of UC and Genetic Susceptibility • UC more common than Crohn’s • Peak incidence between 20-25 YO • Higher prevalence in western countries among white population • First degree relatives have 3 to 20x greater risk of developing IBD • 20% of UC patients have affected relatives
Pathogenesis of IBD • IBD is a Th cell mediated disease • Associated with abnormal MHC antigens. Specifically, UC is associated with HLA-DRB1 • Mouse studies have found a CD4+ variant secreting IL17 to be a culprit • Support for the hygiene hypothesis • Mice infected with Helminths are protected from IBD • Germ-free mice don’t develop IBD • Mice deficient in IL 2 and IL 10 (regulatory cytokines) develop IBD
What type of diarrhoea is present in IBD • Malabsorptive because of damage and eventual destruction of absorptive epithelium • Further loss of function occurs when ulcerations are filled with granulation tissue, fibrosis occurs within the submucosa and resulting disarray of the epithelium
Morphology • Continuous inflammation with no skip lesions of the rectum and sigmoid colon • May involve the entire colon • Pancolitis (proximal involvement) is rare but possible • Broad based pale ulcerations form and can coalesce • Islands of regenerating mucosa form pseudopolyps • Collections of neutrophils in the epithelium forms crypt abscesses which burst causing foreign body reaction within the exposed submucosa • Exposure of the neural plexus to faeces (toxins) results in shutdown of contraction. The colon distends and can rupture (toxic megacolon)