Inflammatory bowel disease (IBD)
• Chronic condition resulting from inappropriate mucosal immune activation. • Two types: • Ulcerative colitis • Crohn disease
• Ulcerative colitis limited to colon and rectum and extends only into mucosa and submucosa • Crohn disease involve any area of GI tract and is transmural • Both present in teens and early 20s • UC slightly more common in females
Ulcerative colitis
Crohn disease
Pathogenesis • Results from combined effects of: • Alterations in host interactions with intestinal microbiota • Intestinal epithelial dysfunction • Aberrant mucosal immune responses • Altered composition of gut microbiome
Genetics • Genetic factors also contribute • Increased risk of disease in family member • Gene most strongly associated with Crohn disease NOD2 (nucleotide oligomerization binding domain 2)
• ATG16L1 (autophagyrelated 16-like), and IRGM (immunity-related GTPase M) • All three involved in recognition and response to intracellular pathogens • Supports hypothesisinappropriate immune reactions to luminal bacteria are important component
Mucosal immune responses • T helper cellsactivated in Crohn disease and response is TH1 type • Certain polymorphisms of IL-23 receptor (involved in development and maintenance of TH17 cells ) confer marked reductions in risk of both Crohn disease and UC
• Pro-inflammatory cytokines TNF, interferon-γ and IL-13, immunoregulatory molecules IL10 and TGF-β, may play role in pathogenesis of IBD.
Epithelial defects • Defects in intestinal epithelial tight junction barrier function Crohn disease • Barrier dysfunction associated with NOD2 polymorphisms
Microbiota • Linkage to NOD2involvement of microbes in Crohn disease • Presence of antibodies against bacterial protein flagellin common in Crohn disease and associated with stricture formation, perforation, and small-bowel involvement • Anti-flagellin antibodies uncommon in ulcerative colitis
Morphology Crohn disease • Occur in any area of GI tract • Most common sites are terminal ileum, ileocecal valve, and cecum • Limited to small intestine (40% of cases), small intestine and colon are both involved in 30%
• Multiple, separate, sharply delineated areas of disease, resulting in skip lesions • Strictures common in Crohn disease • Earliest lesion aphthous ulcer, may progress, and multiple lesions coalesce into serpentine ulcers oriented along axis of bowel
• Patchy distribution results in cobblestone appearance • Fissures may develop between mucosal folds and may extend deeply to become fistula or may perforation
• Intestinal wall thickened and rubbery due to transmural edema, inflammation, submucosal fibrosis, and hypertrophy of muscularis propria stricture formation • Mesenteric fat may extends around serosal surface creeping fat
Microscopic • Clusters of neutrophils within crypt crypt abscesses, crypt destruction • Abrupt transition between ulcerated and adjacent normal mucosa • Repeated cycles of crypt destruction and regeneration lead to distortion of mucosal architecture
• Epithelial metaplasia pseudopyloric or paneth cell metaplasia • Later mucosal atrophy,loss of crypts • Noncaseating granulomas in Crohn disease • Granulomas may also be present in mesenteric lymph nodes
Clinical presentation • Intermittent attacks of mild diarrhea, fever, and abdominal pain. • May present acutely with right lower quadrant pain, fever, and bloody diarrhea mimicing acute appendicitis or bowel perforation
• Asymptomatic periods that last for weeks to months • Re-activation by external triggers physical or emotional stress, specific dietary items, and cigarette smoking
Complications • • • • •
Iron-deficiency anemia Hypoalbuminemia, malabsorption Fibrosing strictures of terminal ileum Fistulae between loops of bowel Perforations and peritoneal abscesses
Extraintestinal manifestations • Uveitis, migratory polyarthritis, sacroiliitis, ankylosing spondylitis, erythema nodosum, and clubbing of fingertips • Pericholangitis and primary sclerosing cholangitis
Ulcerative Colitis • Limited to colon and rectum • Extraintestinal manifestations overlap with those of Crohn disease
Morphology Grossly • Always involves rectum, extends proximally in continuous fashion to involve part or all of colon (pancolitis) • Small intestine normal, mild mucosal inflammation of distal ileum (backwash ileitis) in severe cases of pancolitis
• Involved mucosa slightly red and granular or have extensive broadbased ulcers • regenerating mucosa bulge into lumen pseudopolyps • Fusion of tips of polyps create mucosal bridges
• Chronic disease mucosal atrophy • Mural thickening is not present • Inflammatory mediators can damage muscularis propria disturb neuromuscular function leading to colonic dilation and toxic megacolon risk of perforation
• Histologic features similar to Crohn disease but diffuse and limited to mucosa and superficial submucosa • No granulomas
Clinical Features • Attacks of bloody diarrhea with stringy, mucoid material, lower abdominal pain, and cramps • Temporarily relieved by defecation • Symptoms persist for days, weeks, or months • Smoking may partially relieve symptoms
Differences between CD & UC Features Macroscopic Bowel region Distribution Stricture Wall appearance
CD Ileum +/_colon Skip lesions Yes Thick
UC Colon only Diffuse Rare Thin
Features Microscopic Inflammation Pseudopolyps Ulcers
CD Transmural
Moderate Deep, knifelike Lymphoid rxn Marked Fibrosis Marked Serositis Marked Granulomas Yes (~35%) Fistula/sinuses Yes
UC Limited to mucosa Marked Superficial Moderate Mild to none Mild to none No No
Features Clinical Perianal fistula Fat/vitamin malabsorption Malignant potential Recurrence after surgery Toxic megacolon
CD
UC
Yes (in colonic No disease) Yes No With colonic involvement Common
Yes
No
Yes
No