1. Introduction of Inflammatory bowel disease-Crohn’s disease
Dr Mamlook Elmagraby

2. Objectives of the lecture:
Upon completion of this lecture, students should be able to:
Know the two forms of idiopathic inflammatory bowel disease (IBD)
Describe Crohn disease with respect to: clinical features and extra-intestinal manifestations, pathogenesis, pathology (gross and microscopic features), complications (especially adenocarcinoma preceded by dysplasia)

3. Idiopathic inflammatory bowel diseases
Idiopathic inflammatory bowel diseases include chronic crypt destructive diseases (chronic ulcerative colitis, and Crohn’s disease)
They are chronic relapsing inflammatory disorders of unknown origin which share many common features
Ulcerative colitis and Crohn’s disease differ in:
Natural history
Clinical and pathologic associations
Response to treatment
Relapse (of someone suffering from a disease) suffer deterioration after a period of improvement

4. Idiopathic inflammatory bowel diseases
Pathogenesis:
IBD is characterized by an exaggerated and destructive mucosal immune response
Inflammation is the final common pathway for the pathogenesis of IBD
Both the clinical manifestations and the morphologic changes of IBD are the result of activation of inflammatory cells:
Initially, neutrophils
later in the course, mononuclear cells

5. Idiopathic inflammatory bowel diseases
The products of these inflammatory cells cause nonspecific tissue injury
Inflammation causes:
Impaired integrity of the mucosal epithelial barrier
Loss of surface epithelial cell absorptive function
These events give rise to intermittent bloody diarrhea

6. Idiopathic inflammatory bowel diseases
Etiology:
Genetic susceptibility
Failure of immune regulation
Triggering by microbial flora
Genetic Predisposition
NOD2 has been identified as a susceptibility gene in Crohn disease
Some polymorphisms of the IL-23 receptor gene are protective in both Crohn disease and ulcerative colitis

7. Idiopathic inflammatory bowel diseases
Immunologic Factors
It is not known whether the immune responses in IBD are directed against self-antigens or to bacterial antigens
The primary damaging agents appear to be CD4+ cells
The tissue inflammation may be the result of secretion of the cytokine IL-17 by the "TH17" subset
The inflammatory cytokine TNF may play an important role in Crohn disease

8. Idiopathic inflammatory bowel diseases
Microbial Factors
The sites affected by IBD are flooded with bacteria
It is likely that microbes provide the antigenic trigger to dysregulated immune system

9. One model of IBD pathogenesis
One model of IBD pathogenesis. Aspects of both Crohn disease and ulcerative colitis are shown

10. EXTRAINTESTINAL MANIFESTATIONS OF INFLAMMATORY BOWEL DISEASE

11. Idiopathic inflammatory bowel diseases
Prognosis
The prognosis in a patient with IBD is determined by:
The relapse rate
The rate of surgery
The incidence of colon cancer
About 20% to 30% of patients with pan-UC will require colectomy within their lifetime
More than 60% of Crohn’s patients require surgery

12. Idiopathic inflammatory bowel diseases
The risk for colon cancer is increased in patients with UC In colonic Crohn’s disease, the risk of colorectal cancer is equivalent to that in patients with UC of similar extent and duration The rates of small bowel carcinoma and lymphoma are increased in patients with Crohn’s disease

13. Crohn Disease

14. Crohn Disease
This disease may affect any level of the alimentary tract
It most commonly located at the terminal ileum
Crohn disease must be viewed as a systemic inflammatory disease with predominant gastrointestinal involvement
It occurs at any age but the peak age of detection is the second and third decades of life
Crohn disease occurs three to five times more often among Jews than among non-Jews

15. Crohn Disease Morphology
There is involvement of the small intestine alone in 30% of cases, of small intestine and colon in 40%, and of the colon alone in 30%
The disease is characterized by:
Sharply defined transmural involvement of the bowel by an inflammatory process with mucosal damage
The presence of noncaseating granulomas
Fissuring with formation of fistulae

16. Crohn Disease
Gross:
The sharp demarcation of diseased bowel segments from adjacent uninvolved bowel and skip lesions are characteristic
The serosa becomes granular and dull gray
The mesenteric fat wraps around the bowel surface
The intestinal wall is rubbery and thick
The lumen is narrowed

17. Crohn Disease Early disease shows focal mucosal ulcers, edema
With progressive disease, ulcers join together into long, linear ulcers
Narrow fissures develop between the folds of the mucosa
Further extension of fissures leads to fistula formation

18. Small and large intestines, Crohn disease, mucosal surface
The specimen is a section of normal ileum, thickened ileum, and right colon.
The intestinal wall is thick, the result of edema, inflammation, fibrosis, and hypertrophy of the muscularis propria.
Unlike ulcerative colitis, the diseased areas are sharply demarcated from adjacent uninvolved bowel. Note the area of normal colonic mucosa on the left and area of normal small bowel on the right.
In diseased bowel segments, the serosa is thickened and fibrotic, and often the mesenteric fat wraps around the bowel surface

19. Crohn’s enterocolitis.
Longitudinal ulcers (train track) with intervening normal-appearing mucosa

20. Crohn’s enterocolitis.
Resection specimen with longitudinal ulcers (train track) and intervening normal mucosa

21. Crohn Disease Microscopical features:
The mucosa shows: inflammation, ulceration, chronic mucosal damage
Granulomas may be present
Fibrosis affects all tissue layers
Lymphoid aggregates can be seen
The muscularis mucosae and muscularis propria are thickened

22. Bowel, Crohn disease
focal areas of ulceration,
submucosal edema, and
transmural inflammation with lymphoid nodules
Fissures are narrow microscopic clefts that penetrate from the ulcer surface into muscle and are lined by granulation tissue.
When the entire bowel wall is traversed, a sinus tract is formed that may open to the skin or adhere to an adjacent viscus

23. Bowel, Crohn disease, noncaseating granulomas
Noncaseating granulomas are present in the lamina propria of an uninvolved region of colonic mucosa.
Noncaseating granulomas are present in about half of Crohn disease cases in all tissue layers, both within areas of active disease and in uninvolved regions of the bowel.

24. Crohn Disease Clinical Features
After an initial attack, the manifestations remit either spontaneously or with therapy, but they are followed by relapses
The clinical presentation of Crohn’s disease depends on the section of gastrointestinal tract involved
Symptoms in Crohn’s disease often include:
Right lower quadrant abdominal pain
Fever
Weight loss
Diarrhea
Sometimes a palpable inflammatory mass
Remission diminution of the symptoms of a disease

25. Crohn Disease Hematochezia is less common than in UC
The transmural inflammation in Crohn’s disease can result in the formation of fistulous tracts
Fistulas may form between different segments of bowel or between bowel and skin, bowel and bladder, or rectum and vagina
30% to 40% of patients develop disabling perianal involvement with fissures, fistulas, and abscesses
Chronic inflammation can cause fibrosis and stricture formation, which may result in partial or complete intestinal obstruction

26. Crohn Disease
Strictures can also lead to stasis with subsequent small intestinal bacterial overgrowth Extensive ileal mucosal disease may lead to malabsorption of vitamin B12 and bile salts Weight loss may result from generalized malabsorption caused by loss of absorptive surfaces