06 ibd mbbs

Inflammatory Bowel Disease • Chronic inflammatory condition due to inappropriate mucosal immune activation • Females > males • Present in teens and early 20s IBD

Pathogenesis • Both genetic and environmental factors play important roles • Currently accepted hypothesis- IBD result from combination of – a.Defects in host interactions with intestinal microbiota b.Intestinal epithelial dysfunction c.Aberrant mucosal immune responses

Genetics • Risk increased in family member • Concordance rate of crohn disease for monozygotic twins is approximately 50% and of ulcerative colitis -16%

• NOD2 (nucleotide oligomerization binding domain 2) gene polymorphisms - identified as susceptibility gene in Crohn disease • NOD2 - encodes protein that binds to intracellular bacterial peptidoglycans and activates NF-κB

• NOD2 variants - less effective at recognizing and combating luminal microbes • Microbes enter lamina propria and trigger inflammatory reactions

• In Crohn disease–ATG16L1 (autophagy-related 16-like) and IRGM (immunity-related GTPase M) are important • IRGM - involve in autophagy and clearance of intracellular bacteria

Mucosal immune responses • TH1 and TH17 helper T cells responsible in Crohn disease • Certain polymorphisms of IL-23 receptor confer protection from Crohn disease and ulcerative colitis • IL-23 is involved in development and maintenance of TH17 cells

• Ulcerative colitis - Th2-mediated disease • Increased mucosal IL-13, observed in ulcerative colitis patients.

• Polymorphisms near il-10 gene linked to ulcerative colitis, but not crohn disease,

Crohn disease • • •

•

Morphology Any area of GI tract Most common sites - terminal ileum, ileocecal valve, and cecum Limited to small intestine alone in about 40%, small intestine and colon both involved in 30% and remainder have only colonic involvement Skip lesions - characteristic of Crohn disease

• Earliest lesion - aphthous ulcer, may progress, multiple lesions may coalesce into elongated, serpentine ulcers oriented along axis of bowel

• Edema and loss of normal mucosal texture • Patchy distribution of ulcer results in coarsely textured, cobblestone appearance

• Fissures - between mucosal folds • May extend deeply to become fistula tracts or sites of perforation • Intestinal wall - thickened and rubbery due to transmural edema, inflammation, submucosal fibrosis, and hypertrophy of muscularis propria

• Stricture formation • Extensive transmural diseasemesenteric fat extends around the serosal surface (creeping fat)

Microscopic features • Active lesion - neutrophilic infiltration damage crypt epithelium • Crypt abscesses • Ulceration • Abrupt transition between ulcerated and adjacent normal mucosa

• Epithelial metaplasia - gastric antral-appearing glandspseudopyloric metaplasia • Paneth cell metaplasia may also occur in left colon

• Noncaseating granulomasin approx. 35% • May be present in mesenteric lymph nodes

Clinical Features • Intermittent attacks of mild diarrhea, fever, and abdominal pain • May mimic acute appendicitis or bowel perforation • Active disease followed by asymptomatic periods, lasting for weeks to many months

• Strictures  common in terminal ileum • Fistulae develop between loops of bowel, may also involve urinary bladder, vagina, and abdominal or perianal skin • Perforations and peritoneal abscesses are common

Extra-intestinal manifestations • • • • • • •

Uveitis migratory polyarthritis Sacroiliitis ankylosing spondylitis erythema nodosum, and clubbing of the fingertips pericholangitis and primary sclerosing cholangitis occur in Crohn disease but are more common in ulcerative colitis

Ulcerative colitis • ulcerating inflammatory disease, limited to colon and rectum • extra-intestinal manifestations: 1. migratory polyarthritis 2.Sacroiliitis 3.ankylosing spondylitis 4.Uveitis 5.skin lesions 6.Pericholangitis 7.primary sclerosing cholangitis

Morphology Grossly • involves rectum, extends proximally in continuous fashion • Skip lesions - not seen • small intestine - normal

• Mild mucosal inflammation of distal ileum, backwash ileitis, may be present in severe cases • Colonic mucosa - slightly red and granular or have extensive, broadbased ulcers

• Abrupt transition between diseased and uninvolved colon • Aligned along long axis of colon • Regenerating mucosa bulge into lumen – pseudopolyps • serosal surface - normal

• No strictures • Inflammatory mediators can damage muscularis propria and disturb neuromuscular function leading to colonic dilation and toxic megacolon – increased risk of perforation

Histologic features • crypt abscesses, crypt distortion, and epithelial metaplasia • Inflammation - diffuse and limited to mucosa and submucosa • submucosal fibrosis, mucosal atrophy, and distorted mucosal architecture -residua of healed disease

Clinical Features • Bloody diarrhea with stringy, mucoid material, lower abdominal pain, and cramps – • Temporarily relieved by defecation • May persist for days, weeks, or months • Smoking may partially relieve symptoms.

Differences between UC & CD Feature

CD

UC

MACROSCOPIC Bowel region

Ileum ± colon

Distribution

Skip lesions

Diffuse

Stricture

Yes

Rare

Wall appearance Thick

Colon only

Thin

MICROSCOPIC Inflammation

Transmural

Pseudopolyps

Moderate

Limited to mucosa Marked

Ulcers

Deep, knife-like

Superficial, broad-based Moderate Mild to none Mild to none No No

Lymphoid reaction Marked Fibrosis Marked Serositis Marked Granulomas Yes (âˆź35%) Fistulae/sinuses Yes CLINICAL Perianal fistula Yes (in colonic disease) No Fat/vitamin malabsorption Malignant potential

Yes

No

With colonic involvement Recurrence after surgery Common

Yes

Toxic megacolon

Yes

No

No