INFLAMMATORY BOWEL DISEASE (Robbins pp 815)

Pathophysiology: Usually there are luminal factors that act as antigens therefore stimulating the intestines immune system. In this case, normal luminal factors stimulate inappropriate immune responses causing ongoing inflammation, because the integrity of intestinal epithelium is lost. So, the immune system inappropriately activates.

Genetic factors: Mainly, CD has greater genetic contribution than UC.

Cofactors and Environment: NALS ≫ N = NSAIDS can lead to disease flare ups ≫ A = appendicectomy associated with decreased incidence of UC ≫ L = luminal factors requisite for IBD ≫ S = smoking protects against UC but increases risk of CD.

IBD and immune response: The belief is that there is inappropriate activation of the mucosal immune system. Now does it activate because there is something inherently wrong with the mucosal immune system or does it activate because there is something inherently wrong with the mucosal barrier mechanisms? This question is not answered properly yet. Patients with CD have lots of CD4+ cells with Th1 phenotype that produce IF-g + IL-2. Patients with UC have lots of CD4+ cells with Th2 phenotype that products TGF-b + IL-5. Once the immune system is activated then it results in production of non-specific inflammatory mediators which cause non-specific tissue damage. These mediators further recruit other leukocytes from the vasculature so the inflammation is ongoing.

Category: Pathology Notes