Ulcerative Colitis : Pathogenesis-I
Image Description
The etiology of both ulcerative colitis (UC) and Crohn disease is unknown; however, there appears to be a complex interplay of genetic susceptibility, host immunity, and environmental factors. Several pathways are involved, including: 1) altered host interaction with intestinal microbiota; 2) intestinal epithelial dysfunction; 3) inappropriate activation of mucosal immune responses; and 4) altered composition of gut microbiome in a susceptible host.
Role of Genetics: Genetics factors contribute to the risk of inflammatory bowel disease (IBD). The influence of genetic factors is much greater in Crohn disease as compared to UC. The concordance rates for monozygotic twins for developing Crohn disease and UC are 50% and 15% respectively. For dizygotic twins, the concordance rate for both forms of IBD is less than 10%.
More than 160 genes associated with IBD have been identified. Any single gene confers only a small risk of developing the disease. Many of these genes are common to other immune-mediated disorders. Amongst the genes strongly associated with Crohn disease are NOD2 (nucleotide oligomerization binding domain 2), ATG16L1 (autophagy-related 16-like), and IRGM (immunity-related GTPase M). All three genes encode proteins that are components of autophagy pathways and are involved in recognition of and response to intracellular bacteria.
This colectomy specimen with ulcerative colitis shows numerous pseudopolyps in the affected segment. For detailed gross pathologic features of UC, go to slides 6-15.
Role of Genetics: Genetics factors contribute to the risk of inflammatory bowel disease (IBD). The influence of genetic factors is much greater in Crohn disease as compared to UC. The concordance rates for monozygotic twins for developing Crohn disease and UC are 50% and 15% respectively. For dizygotic twins, the concordance rate for both forms of IBD is less than 10%.
More than 160 genes associated with IBD have been identified. Any single gene confers only a small risk of developing the disease. Many of these genes are common to other immune-mediated disorders. Amongst the genes strongly associated with Crohn disease are NOD2 (nucleotide oligomerization binding domain 2), ATG16L1 (autophagy-related 16-like), and IRGM (immunity-related GTPase M). All three genes encode proteins that are components of autophagy pathways and are involved in recognition of and response to intracellular bacteria.
This colectomy specimen with ulcerative colitis shows numerous pseudopolyps in the affected segment. For detailed gross pathologic features of UC, go to slides 6-15.