Genelic/Autoimmue association With HLA-627 exact panto to know? Ufcerative Colitis Pathogenesis and Pathophysiology IT lymphyale TH2 Myraclive Plasma cells Teev stays colon originates from rectum-prochis neuhaphils have a prolien that looks like that of pathogen Anki-bodies Environment 1 dict antibiokico infectious direct damage No compelety 2 PROTECTIVE Haive Tcell affected mucin basrier & fce's of barrier boluen lumen ↑ ptimealbility of light Junctions between spr celli APC co-shirnulation epl sary bacdera translocation Bran lumen to gut wal Phagocytosis 12-1 naive B cells INF •cytokines 1-6 11-4 12-12 Coony in UC NOI CO destroy protions in kosues Antibodico CP-ANCA) Plasma Cells margination diapedia CAMS T expression of destroy ⇒HOLECULAR HINCKRY isflammati neutrophils frodearses ROS destroy issuro bind lea lammatio inkgrins. cell adhesion molecules bloedsheaney +12-5 112-13 hyperactive TH naive T cells a bit of TH some. naive T cell unknown alokines? mamine cal destory tells te GIT Cytoxic cells naive T cells Local Manifestations & Complications Strictures Start from flares, remissions Significant inability Spread ball to distal colitis Matter stuck Proctalgia Extended sigmoid Proctosigmoiditis Rectal pain Esp. in defecation Tenesmus Increased stool frequency Small dilation Continuous more more watery stools Hardening Blood loss in stools Bloody diarrhea Ulcerations Heal once via fibrosis When not healed via fibrosis Lumen narrowing Distal colitis Abdominal distension Nausea Vomiting Need repair ↑ risk of oncogenesis ↑ inflammation + ↑ risk of magnetic plexus ↓ SM relaxation Bowel dilation ↑ SM contraction Thin walls ↑ risk of perforation Thin walls with large lumen (>6 cm) Bacteria leak ↑ WBC Sepsis Hemodynamic instability Altered mental states ↑ HR Abbreviations: BO: Bowel obstruction G: Graded LLO: Left lower quadrant PCRC: Pouchitis Crohn's colitis SM: Smooth muscle SYSTEMIC MANIFESTATIONS & COMPLICATIONS Cytokine release → ↑ many ads IL-1, IL-4, TNF-α, IL-6, IL-8, IL-17, etc. ↑ acute phase reactants Hypothalamus pool → fever PGE → post-meal weakness ↑ IL-1 receptor antagonist ↓ IL-1 ↓ fever GI bleeding Mainly ulcerations May be chronic ↑ IP ↓ Hb Jaundice ↑ GGT, alkaline phosphatase ↑ bilirubin Joint pain Axial or peripheral Sacroiliitis Spondylitis Osteoarthritis Enthesitis Eye manifestations Iritis Episcleritis Scleritis Conjunctivitis Skin manifestations Erythema nodosum Pyoderma gangrenosum Psoriasis Atopic dermatitis Biliary ducts ↑ risk of sclerosing cholangitis Strictures of GIT wall Mucosa Submucosa Muscularis externa Serosa/Adventitia ↑ fibrosis Lumen narrowing Obstruction ↑ risk of perforation Encapsulated pocket of immune cells + dead tissue cells Crypt abscess Abbreviations: GIT: Gastrointestinal tract IL: Interleukin TNF-α: Tumor necrosis factor-alpha PGE: Prostaglandins IP: Iron profile GGT: Gamma-glutamyl transferase UC: Ulcerative colitis