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inflammatory bowel disease

الكلية كلية طب حمورابي     القسم الكلية ذات القسم الواحد     المرحلة 4
أستاذ المادة هديل عبد الاله رزوقي كربل       23/10/2016 19:55:04
Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is a chronic condition resulting from inappropriate mucosal immune activation. IBD encompasses two major entities, Crohn disease and ulcerative colitis.
Ulcerative colitis is limited to the colon and rectum and extends only into the mucosa and submucosa.
By contrast, Crohn disease, which also has been referred to as regional enteritis (because of frequent ileal involvement), may involve any area of the gastrointestinal tract and frequently is transmural.

Epidemiology
Both Crohn disease and ulcerative colitis are more common in females and frequently present during adolescence or in young adults.
The geographic distribution of IBD is highly variable, but it is most prevalent in North America, northern Europe, and Australia. IBD incidence worldwide is on the rise and is becoming more common in regions in which the prevalence was historically low. The hygiene hypothesis suggests that these changes in incidence are related to improved food storage conditions and decreased food contamination. Specifically, it proposes that a reduced frequency of enteric infections due to improved hygiene has resulted in inadequate development of regulatory processes that limit mucosal immune responses early in life. As a result, exposure of susceptible individuals to normally innocuous microbes later in life triggers inappropriate immune responses that may be self-sustaining due to loss of intestinal epithelial barrier function.

PATHOGENESIS
Most investigators believe that IBD results from a combination of errant host interactions with intestinal microbiota, intestinal epithelial dysfunction, and aberrant mucosal immune responses.
Genetics. Risk of disease is increased when there is an affected family member, Molecular linkage analyses of affected families have identified NOD2 (nucleotide oligomerization binding domain 2) as a susceptibility gene in Crohn disease. NOD2 encodes a protein that binds to intracellular bacterial peptidoglycans and subsequently activates NF-?B. It has been postulated that disease-associated NOD2 variants are less effective at recognizing and combating luminal microbes, which are then able to enter the lamina propria and trigger inflammatory reactions.

Mucosal immune responses. Although the mechanisms by which mucosal immunity contributes to the pathogenesis of ulcerative colitis and Crohn disease are still being deciphered, immunosuppressive and immunomodulatory agents remain mainstays of IBD therapy.
Overall, it is likely that some combination of derangements that activate mucosal immunity and suppress immunoregulation contribute to the development of both ulcerative colitis and Crohn disease.

Epithelial defects A variety of epithelial defects have been described in Crohn disease, ulcerative colitis, or both. For example, defects in intestinal epithelial tight junction barrier function are present in patients with Crohn disease and a subset of their healthy first-degree relatives. This barrier dysfunction cosegregates with specific disease associated NOD2 polymorphisms.

Microbiota. Despite a growing body of data that suggest that intestinal microbiota contribute to IBD pathogenesis, their precise role remains to be defined. In keeping with this, some antibiotics, such as metronidazole, can be helpful in maintenance of remission in Crohn disease. Ongoing studies suggest that ill-defined mixtures containing probiotic, or beneficial, bacteria also may combat disease in experimental models, as well as in some patients with IBD, although the mechanisms responsible are not well understood.
One model that unifies the roles of intestinal microbiota, epithelial function, and mucosal immunity suggests a cycle by which transepithelial flux of luminal bacterial components activates innate and adaptive immune responses. In a genetically susceptible host, the subsequent release of TNF and other immune-mediated signals direct epithelia to increase tight junction permeability, which further increases the flux of luminal material. These events may establish a self-amplifying cycle in which a stimulus at any site may be sufficient to initiate IBD.



Crohn Disease
MORPHOLOGY
The most common sites involved by Crohn disease at presentation are the terminal ileum, ileocecal valve, and cecum.
The presence of multiple, separate, sharply delineated areas of disease, resulting in skip lesions, is characteristic of Crohn disease and may help in differentiation from ulcerative colitis. Strictures are common.
The earliest lesion, the aphthous ulcer serpentine ulcers oriented along the axis of the bowel.
Sparing of interspersed mucosa results in a coarsely textured, cobblestone appearance in which diseased tissue is depressed below the level of normal mucosa .
Fissures frequently develop between mucosal folds and may extend deeply to become sites of perforation or fistula tracts. The intestinal wall is thickened as a consequence of transmural edema, inflammation, submucosal fibrosis, and hypertrophy of the muscularis propria,
Mesenteric fat frequently extends around the serosal surface (creeping fat).
The microscopic features of active Crohn disease include:
--abundant neutrophils that infiltrate and damage crypt epithelium. Clusters of neutrophils within a crypt are referred to as a crypt abscess and often are associated with crypt destruction.
--Repeated cycles of crypt destruction and regeneration lead to distortion of mucosal architecture
--Noncaseating granulomas a hallmark of Crohn disease, are found in approximately 35% of cases and may arise in areas of active disease or uninvolved regions in any layer of the intestinal wall Granulomas also may be found in mesenteric lymph nodes.
The absence of granulomas does not preclude a diagnosis of Crohn disease.

Clinical Features
In most patients, disease begins with intermittent attacks of relatively mild diarrhea, fever, and abdominal pain. Approximately 20% of patients present acutely with right lower quadrant pain, fever, and bloody diarrhea that may mimic acute appendicitis or bowel perforation. Periods of active disease typically are interrupted by asymptomatic intervals that last for weeks to many months.
Iron deficiency anemia may develop in persons with colonic disease, while extensive small bowel disease may result in serum protein loss and hypoalbuminemia, generalized nutrient malabsorption, or malabsorption of vitamin B12 and bile salts. Fibrosing strictures, particularly of the terminal ileum, are common and require surgical resection.
Extraintestinal manifestations of Crohn disease include uveitis, migratory polyarthritis, sacroiliitis, ankylosing spondylitis, erythema nodosum, and clubbing of the fingertips, any of which may develop before intestinal disease is recognized. Pericholangitis and primary sclerosing cholangitis also occur in Crohn disease but are more common in ulcerative colitis.

Ulcerative Colitis
MORPHOLOGY
Ulcerative colitis always involves the rectum and extends proximally in a continuous fashion to involve part or all of the colon. Skip lesions are not seen.
On gross evaluation, involved colonic mucosa may be slightly red and granular-appearing or exhibit extensive broad-based ulcers. Ulcers are aligned along the long axis of the colon but typically do not replicate the serpentine ulcers of Crohn disease
Isolated islands of regenerating mucosa often bulge into the lumen to create small elevations, termed pseudopolyps.
Unlike in Crohn disease, mural thickening is absent, the serosal surface is normal, and strictures do not occur.
However, inflammation and inflammatory mediators can damage the muscularis propria and disturb neuromuscular function leading toc olonic dilation and toxic megacolon, which carries a significant risk of perforation.
Histologic features of mucosal disease in ulcerative colitis are similar to those in colonic Crohn disease and include inflammatory infiltrates, crypt abscesses, crypt distortion, and epithelial metaplasia. However, skip lesions are absent and inflammation generally is limited to the mucosa and superficial submucosa. Granulomas are not present.

Clinical Features
Ulcerative colitis is a relapsing disorder characterized by attacks of bloody diarrhea with expulsion of stringy, mucoid material and lower abdominal pain and cramps that are temporarily relieved by defecation. These symptoms may persist for days, weeks, or months before they subside, and occasionally the initial attack may be severe enough to constitute a medical or surgical emergency.

Features That Differ between Crohn Disease and Ulcerative Colitis
MACROSCOPIC
Bowel region Ileum ± colon Colon only
Distribution Skip lesions Diffuse
Stricture Yes Rare
Wall appearance Thick Thin
MICROSCOPIC
Inflammation Transmural Limited to mucosa
Pseudopolyps Moderate Marked
Ulcers Deep, knife-like Superficial, broad-based
Lymphoid reaction Marked Moderate
Fibrosis Marked Mild to none
Serositis Marked Mild to none
Granulomas Yes (?35%) No
Fistulae/sinuses Yes No
CLINICAL
Perianal fistula Yes (in colonic disease) No
Fat/vitamin malabsorption Yes No
Malignant potential With colonic involvement Yes
Recurrence after surgery Common No
Toxic megacolon No Yes


المادة المعروضة اعلاه هي مدخل الى المحاضرة المرفوعة بواسطة استاذ(ة) المادة . وقد تبدو لك غير متكاملة . حيث يضع استاذ المادة في بعض الاحيان فقط الجزء الاول من المحاضرة من اجل الاطلاع على ما ستقوم بتحميله لاحقا . في نظام التعليم الالكتروني نوفر هذه الخدمة لكي نبقيك على اطلاع حول محتوى الملف الذي ستقوم بتحميله .