Inflammatory bowel disease “IBD” : A chronic relapsing idiopathic inflammatory disorders of GIT likely resulting from unregulated and exaggerated local immune response to normal gut flora and self antigen in susceptible individuals. * a group of chronic intestinal diseases characterized by inflammation of the bowel The most common types : Ulcerative collitis & crohn disease The most common types : Ulcerative collitis & crohn disease
IBD pathogenesis Normally there is balance B/w : 1- factors increasing immune system. 2- host defense that down-regulate inflammation & maintain the integrity of mucosa. Pathogenesis involves tissue injury by these factors: 1- genetic : -first-degree relatives are 3 to 20 times more likely to develop diseas - HLA-DRB1 with U.C., HLA-DR7 and DQ4 with C.D.. - NOD2 is mutated in as many as 25% of C.D.. The NOD2 protin is a component of the cell walls of many bacteria and its expressed in paneth cells. The disease associated mutant form may be defective in responding to bacteria then allowing chronic infection to be established in the intestine and promoting inflammatory reactions by NOD2 –independent pathways Mutation in IL-23 receptor gene stimulation of IL-17 inflammatory reaction(C.D. and U.C.).
2- immunologic :- CD4+ is a primary damaging agent. IL17 from TH17. Effectiveness of TNF antagonists indicate involvement of TNF in C.D. 3- microbial :- ileum and colon are filled with bacteria more likely to provide antigenic trigger to a fundamentally dysregulated immune system.
IBD pathogenesis “cont” : Inflammation is the final pathway of pathogenesis. Inflammation causes : 1- impaired integrity of mucosal epithelial barrier. 2- loss of surface epithelial cell absorptive function. Collectively these give rise to intermittent bloody diarrhea
Crohn’s disease: It is characterized by : Sharply limited transmural involvement of the bowel by an inflammatory process with mucosal damage. 1 Noncaseating granuloma. 2 2 Fistula formation. 3 It may affect any level of GIT, but mostly at the terminal ileum.
Morphology : Macroscopic 1-sharply delimited and typically transmural involvement of the bowel by an inflammatory process with mucosal damage 2-noncaseating granulomas 40%-60% 3- fissuring with formation of fistulae 4- in diseased segments the serosa becomes granular and dull gray and often the mesenteric fat wraps around the bowel surface(creeping fat) 5- the intestinal wall is rubbery and thick the result of edema,inflammation,fibrosis and hypertrophy of muscularis propria
Microscopic: abundant neutrophils that infiltrate and damage crypt epithelium transmural inflamation -crypt abscesses -ulceration is common -and adjacent normal mucosa -lesions are patchy Noncaseeating granulomas -granulomas may in mesenteric lymph nodes -fibrosing st rictures later on
12 ♥ Recurrent episodes of diarrhea ♥ Crampy abdominal pain ♥ constipation ♥ Fever for days to weeks ♥ Melena 50% in colon involvement Clinical features ♥ Malabsorption syndrome ♥ Fistula formartion ♥ Anal lesions ♥ Extra intestinal: uveitis, migratory polyarthritis, erythema nodosum, ♥ bile duct inflammatory disorders, and obstructive uropathy with attendant nephrolithiasis. ♥ Abdominal abscess and peritonitis ♥ Intestinal stricture or obstruction ♥ Massive bleeding “rare” ♥ Toxic dilation of colon “rare “ ♥ Carcinoma 5-6 times “less than U.C.” Complications :
Ulcerative colitis: Ulceroinflammatory disease affecting Only the colon “it begins in rectum and extend proximally and may involve the entire colon”. It is limited to mucosa and submucosa except in most sever cases.
Morphology : Macroscopic ♥ It is continuous starting from colon “no skip lesion”. ♥ Destruction of mucosa, hyperemia, edema, granularity with friability and easy bleeding. ♥ Broad-base ulceration of mucosa. ♥ Regenerating mucosa bulge upward to create pseudopolyps. ♥ Interconnection of edges of adjacent ulcers create tunnels covered by tenuous mucosal bridges. ♥ Ulcers are aligned along the axis of the colon. ♥ Rarely, perforation and pericolonic abscess formation. ♥ exposure of muscularis propria and neural plexus to fecal material may lead to complete shutdown of neuromuscular function. ♥ Colon swell and become gangrenous (toxic megacolon). ♥ Progressive mucosal atrophy leads to flattened and attenuated mucosal surface.
Microscopic: ♥ ● Mononucleare inflammatory cells in lamina propria. ♥ ● Crypt abscess “neutrophils in epithelial layer. ♥ ● There is no granuloma, although rupture of crypt abscess may incite a foreign body reaction. ♥ ● With remission,granulation tissue fills in the ulcer craters then mucosal epithelium regeneration. ♥ ● Submucosal fibrosis and mucosal architectural disarray and atrophy remain as residua of healed disease.
1 2 Clinical features:- Complications: ♥ Bloody mucoid diarrhea ♥ Cramps, lower abdominal wall “relieved with defecation” ♥ Fever &weight loss ♥ Bloody stool is more in UC than CD ♥ Cancer is times increase risk “higher than CD” ♥ Blood loss anemia ♥ Diarrhea electrolytes disturbance ♥ Extra intestinal :migratory polyarthritis “more than CD”, sacroiliitis, ankylosing spondylitis, uveitis, erythema nodosum. ♥ severe colonic dilation (toxic megacolon) with potential rupture, and perforation with peritonitis
Differences Between Crohn’s Disease And Ulcerative Colitis Both are disease which are diagnosed by excluding other common disorders e.g. infectious enterocolitis (Shigella, Salmonella), Ischemic bowel disease and appendicitis. -They are two diseases which have some similarities and some differences. Crohn disease : Granulomatous IBD affecting any portion of gut, specially ileum and sometime colon Ulcerative colitis: IBD without granuloma formation affecting only the colon
Ulcerative colitisCrohn disease (small intestine) Crohn disease (colon) Feature(gross) Colon onlyIleum 30% with colon 40% Colon 30%Bowel region DiffuseSkip lesion Distribution Late/ rareearlyVariableStricture thinthickenedvariableWall appearance yesnoyesDilation
General differences between crohn’s disease and ulcerative colitis Ulcerative colittisCrohns diseaseFactor Intermittent attacks of bloody mucoid,diarrhea, abdominal pain, Exteraintestinal manifestation include migority polyarthritis and sarcolitis Intermittent attacks of diarrhea,fever, abdominal pain,anorexia, weight loss, Intervening asymptomatic periods Exteraintestinal manifestation include migority polyarthritis and sarcolitis Clinical appearance YesMuch less than UCMalignant potential NoYesFat/vitamin malabsorption goodpoorResponse to surgery
Describe non-pharmacological measures used in treatment of IBD and mention the goals of treatment Goals of treatment: - Induce and maintain remission. - Limit drug toxicity. - Modify the pattern of disease. - Avoid complications. - Diagnose malignancy early. Non-pharmacological measures: 1- Nutrition support. 2- Surgery. Non-pharmacological measures: 1- Nutrition support. 2- Surgery.
1- Nutritional support : A. Low lactose diet: to avoid problems of malabsorption. B. Low fiber diet: to reduce symptoms of intestinal obstruction in crohn’s disease. C. Replacement therapy: with iron, protein, water and fat-soluble vitamins, trace elements and electrolytes. D. Total parenteral nutrition if there is : - loss of appetite. - severe illness. - extensive bowel resection - preparation for surgery. - children or adolescent with growth retardation because of crohn’s disease.
2-Surgery % of patients with UC and % of patients with Crohn’s disease require surgical intervention at some point in their life. ♥ Indication of surgery in crohn disease is for complications like: ♥ - Bowel obstruction. ♥ - Abscess or fissures in the anal area. ♥ - Perforations in the large intestine. ♥ - Cancer or precancerous tissue. ♥ - Severe disease that does not respond to other treatment. ♥ - Severe bleeding that requires ongoing blood transfusions. ♥ Indications of surgery in ulcerative colitis : ♥ 1 Uncontrolled disease after maximal medical therapy. ♥ 2 Severe complications of the disease such as : ♥ Colonic perforation. ♥ Toxic dilation of the colon(megacolon) ♥ Uncontrolled colonic hemorrhage ♥ Colonic stricture ♥ Long-standing disease (>8y) ♥ High risk of cancer development (prophylaxis).
List drugs used in treatment of IBD: 1 Aminosalicylates Mesalazine Olsazine Corticosteroids prednisolone hydrocotizone 2 3 Immunosuppressants: Thiopurin Methotrexate Cyclosporin
Crohn’s diseaseUlcerative colitisFeature Whole GITColon and rectumInvolvement PresentAbsentSkip lesions Whole intestinal wall Mucosa and submucosa Transmural infection +++++Crypt abscesses +++++Deep fissures Pseudopolyps ++(50%)NoGranuloma formation ++++Broad ulcers ++++early+lateTransmural fibrosis ++++premalignant poorgoodresponse to surgery