Inflammatory Bowel Disease Midterm Notes PDF

5 1 GASTROINTESTINAL – Inflammatory Bowel Disease Inflammatory Bowel Disease (IBD) is a chronic, relapsing, and remi2ng inflammatory disorder of the gastrointes7nal (GI) tract. The two main forms of IBD are:...

5 1 GASTROINTESTINAL – Inflammatory Bowel Disease Inflammatory Bowel Disease (IBD) is a chronic, relapsing, and remi2ng inflammatory disorder of the gastrointes7nal (GI) tract. The two main forms of IBD are: 1. Crohn’s Disease (CD) 2. Ulcera9ve Coli9s (UC) 1. Most Likely Cause Cause: o Unknown e9ology. IBD is thought to be caused by an aberrant immune response to intes9nal microbiota in a gene7cally suscep7ble individual. o Gene9c Component: § NOD2/CARD15 gene muta9on: Muta7ons in this gene, located on chromosome 16, are linked to Crohn’s disease (CD). § Gene7c predisposi7on is supported by twin studies, where monozygo7c twins have a higher concordance rate (42%-58%) than dizygo7c twins (0%-5%). o Microbial Dysbiosis: Imbalance of gut microbiota is thought to play a role in immune system ac7va7on. o Environmental Triggers: Smoking is a risk factor for Crohn's disease but may be protec7ve for ulcera7ve coli7s. 2. Pathophysiology The pathophysiology of IBD differs between Crohn’s Disease and Ulcera9ve Coli9s, but both are driven by immune dysregula7on. Crohn’s Disease (CD) Loca9on: Can affect any part of the GI tract from mouth to anus, but is most common in the terminal ileum and proximal colon. Nature of Inflamma9on: o Transmural Inflamma9on: Involves the full thickness of the GI wall. o Skip Lesions: Areas of normal 7ssue between inflamed regions. Immune Response: o Predominantly mediated by Th1 T helper cells, which release TNF-α and recruit inflammatory macrophages. o Th17 T cells also contribute to the inflammatory process. Tissue Changes: o Development of fistulas, perfora9ons, and abscesses due to transmural inflamma7on. o Fibrosis and scar 7ssue forma7on cause strictures and bowel obstruc9on. Ulcera9ve Coli9s (UC) Loca9on: Begins in the rectum and extends proximally in a con9nuous paZern throughout the colon. Nature of Inflamma9on: o Involves only the mucosa and submucosa (not transmural).  2 o Con9nuous Inflamma9on without "skip lesions". Immune Response: o Predominantly mediated by Th2 T helper cells, leading to B-cell ac9va9on and produc7on of an7bodies. o Th17 T cells are also implicated in the inflammatory process. Tissue Changes: o Forma7on of pseudopolyps (inflammatory polyps). o Crypt distor9on and crypt abscesses due to neutrophilic infiltra7on. o Loss of goblet cells results in reduced mucus produc7on. 3. Disease Transmission Transmission: o Not transmissible. IBD is a non-communicable disease. o The role of microbiota suggests that gut flora imbalances may be involved, but these are not transmi[ed from person to person. 4. Risk Factors The risk factors for IBD include gene9c, environmental, and lifestyle factors. Gene9c Risk Factors Gene9c Suscep9bility: Concordance in monozygo7c twins is higher (42-58%) than in dizygo7c twins (0-5%), highligh7ng a gene7c component. NOD2/CARD15 Muta9ons: These muta7ons increase the risk of Crohn’s disease by affec7ng the recogni7on of bacterial components. Other Gene Muta9ons: Other chromosomal loci have been linked to IBD, indica7ng a polygenic inheritance paZern. Environmental Risk Factors Smoking: o Increases risk for Crohn’s disease. o Paradoxically, smoking may be protec9ve against ulcera9ve coli9s. Diet: o Diets high in sugar and refined carbohydrates are associated with increased IBD risk. Microbial Dysbiosis: o Disrup7on of gut flora may promote immune dysregula7on and trigger IBD. o An7bio7c use has been associated with changes in gut microbiota, possibly contribu7ng to IBD development. Lifestyle and Socioeconomic Risk Factors Geographical Loca9on: o Higher prevalence of IBD in developed countries. Race/Ethnicity: o Higher prevalence of IBD among Ashkenazi Jews and white popula9ons. Hygiene Hypothesis: o Improved sanita7on may reduce exposure to infec7ous agents, leading to an overac7ve immune system and higher IBD risk.  3 Summary Table Criteria Crohn’s Disease (CD) Ulcera9ve Coli9s (UC) Gene9c predisposi9on Gene9c predisposi9on (polygenic), Cause (NOD2/CARD15), environmental microbial dysbiosis. factors, microbial dysbiosis. Transmural inflamma9on, skip Mucosal inflamma9on, con7nuous lesions, driven by Th1 T cells, lesions from rectum upward, driven by Pathophysiology forma7on of fistulas, abscesses, and Th2 T cells, forma7on of pseudopolyps strictures. and crypt abscesses. Transmission Not transmissible. Not transmissible. Smoking, gene7c suscep7bility Non-smokers at higher risk, gene7c Risk Factors (NOD2), microbial dysbiosis. suscep7bility, microbial dysbiosis. Clinical Manifesta9ons Crohn's Disease Abdominal pain: Usually in the right lower quadrant. Diarrhea: Oden non-bloody. Fistulas, abscesses, and strictures can develop. Weight loss and nutri9onal deficiencies due to malabsorp7on. Ulcera9ve Coli9s Diarrhea: Oden accompanied by bloody, purulent mucus. Cramping pain: Usually in the lower led quadrant. Bowel urgency and tenesmus (feeling of incomplete defeca7on). Fever, anemia, and weight loss in severe cases.