IBD Inflammatory Bowel Disease(IBD) is

currently presumed to result from the aggregate effect of inherited variants of

genes conferring risk of disease and environmental factors affecting the

immune system, which combined lead to an aberrant inflammatory response.

THE INFLAMMATORY CASCADE IN IBD

Inflammatory response is perpetuated by T-cell activation Inflammatory cytokines, such as L-1, IL-6, and TNF, have diverse effects on tissues.

They promote fibrogenesis, collagen production, activation of tissue metalloproteinases, and the production of other inflammatory mediators; they also activate the coagulation cascade in local blood vessels.

IBD Locus a Chromosome Gene b PhenotypeIBD1 16q CARD15 CD

IBD2 12p --- DC,UC

IBD3 6p MHC? CD

IBD4 14q --- CD

IBD5 5q OCTN? CD

IBD6 19p --- CD,UC

REPLICATED GENETIC LOCI IN IBD

CROHN’S DISEASE ULCERATIVE COLITIS

It is associated with HLA,DR1/DQw5 and NOD2 genes and an abnormal T-cell response particularly,CD4+T cell (TH1 cells).

It is chronic granulomatous disease which can be affect any part of the gut

Associate with HLA-DR2 polymorphism in IL-10 gene and an abnormal T-cell response particularly of CD4+ T cells ( TH2cells).

Defective immune regulation in IBD

Clinical Ulcerative Colitis Crohn’s Disease

Gross blood in stool Yes Occasionally

Mucus Yes Occasionally

Systemic symptoms Occasionally Frequently

Pain Occasionally Frequently

Abdominal mass Rarely Yes

Significant perineal disease No Frequently

Fistulas No Yes

Small-intestinal obstruction No Frequently

Colonic obstruction Rarely Frequently

Response to antibiotics No Yes

Recurrence after surgery No Yes

ANCA-positive Frequently Rarely

ASCA-positive Rarely Frequently

DIFFERENT CLINICAL, ENDOSCOPIC, ANDRADIOGRAPHIC FEATURES

Endoscopic Ulcerative Colitis Crohn’s Disease

Rectal sparing Rarely Frequently

Continuous disease Yes Occasionally

“Cobblestoning” No Yes

Granuloma on biopsy No Occasionally

Radiographic Ulcerative Colitis Crohn’s Disease

Small bowel significantly abnormal

No Yes

Abnormal terminal ileum Occasionally Yes

Segmental colitis No Yes

Asymmetric colitis No Yes

Stricture Occasionally Frequently

Colonoscopy is the procedure of choice

Sigmoidoscopy examines the colon up to the splenic flexure and is currently used to exclude distal colonic inflammation or obstruction in young patients not at significant risk for colon

cancer. For elusive capsule endoscopy, or the novel technique of double-balloon enteroscopy.

MORPHOLOGY

CD• The earliest lesion in crohn’s is the

aphthous ulcer. Many such ulcers may fuse together to form serpentine ulcer arranged longitudinally.

• Grossly, involved bowel segment typically has a rigid, strictured or thickened wall with creeping fat.

• Full thickness of the intestine is affected in the disease i.e there is transmural inflammation. This causes weakness in the wall there by leading to fissure and fistula formation in Crohn’s disease. Fibrosis is also commoner in this type IBD. Perianal fistula is the most common fistula seen .

UC The disease involves the entire colon

(pancolitis )starting from the rectum (retrograde involvement). There is presence of regenrating mucosa which projects in the lumen and is called “pseudopolyps”.

• In extreme cases, there is involvement of the nerve plexus in the muscularis layer resulting in decrese in the motility of the colon and increase in its size over a period of time giving rise to “toxic megacolon”

• The characteristic feature of the disease is mucosal damage continuously from the rectum and extended proximally. This may also lead to “backwash ileitis”. This type of IBD is more commonly associated with progression of the development of cancer.

• There is patchy involvement of the intestine which is known as presence of “skip lesion”. The intervening area between two affected portions is absolutely normal. So, the mucosa appears to be irregular which is unknown as “cobblestone mucosa.”

• There is a presence of non-caseating granulomas.

• Clinical features are intermittent attacks of abdominal pain, blood in stools, fever steatorrhoea and megaloblastic anemia (the last two features result because there is impairment in the absorption of bile acids and vitamin B12 respectively from the ileum).

Screeing test is presence of ASCA . ABformation is common against cell wallof yeast , sacchromyces cerevisae inpatients with crohn’s disease.

• There is absence of granulomas.

Clinical features are : intermittentattacks of abdominal pain, bloodymucoid stools and fever.

There is presence of p-ANCA.

Medical management of IBD.

Medical management of IBD.

Indication for surgery

Ulcerative Colitis• Intractable disease• Fulminant disease• Toxic megacolon• Colonic perforation• Massive colonic hemorrhage• Extracolonic disease Abscess• Colonic obstruction• Colon cancer prophylaxis• Colon dysplasia or cancer

Crohn’s Disease• Small Intestine• Stricture and obstruction unresponsive

to medical therapy.• Massive hemorrhage• Refractory fistula• Colon and Rectum• Intractable disease• Fulminant disease• Perianal disease unresponsive to• medical therapy• Refractory fistula• Colonic obstruction• Cancer prophylaxis• Colon dysplasia or cancer

Novel agents currently under investigation for treating inflammatory bowel disease

Kings college of London (NHS)

Kings college of London (NHS

Kings college of London (NHS

Waiting for your answer !

Blossom Sabi :)