1. Inflammatory bowel disease

2. Inflammatory bowel disease
refers to two chronic diseases that cause inflammation of the intestines: ulcerative colitis and Crohn's disease.
Although the diseases have some features in common, there are some important differences.

3. Inflammatory bowel disease
Medical research hasn't determined yet what causes inflammatory bowel disease. But researchers believe that a number of factors may be involved, such as
environment
diet
possibly genetics

4. Inflammatory bowel disease
Current evidence suggests that there's likely a genetic defect that affects how our immune system works and how the inflammation is turned on and off in those people with inflammatory bowel disease, in response to an offending agent, like:
bacteria
a virus
or a protein in food

5. Epidemiology of IBD Ulcerative colitis Crohn’s disease 11/100 000
Incidence (US)
11/ 7/
Age of onset
15-30 & 60-80
Male:female ratio
1:1
1,1-1,8:1
Smoking
May prevent disease
May cause disease
Oral contraceptive
No increased risk
Relative risk 1,9
Appendectomy
Not protective
Protective
Monozygotic twins
8% concordance
67% concordance

6. Genetics
Studies suggested that 1st degree relatives of an affected patient have a risk of IBD that is 4-20 times higher than that of general population.
The best replicated linkage region, IBD1, on chromosome 16q contains the CD susceptibility gene, NOD2/CARD15.
Having one copy of the risk alleles confers a 2–4-fold risk for developing CD, whereas double-dose carriage increases the risk 20–40-fold.

7. Etiology
Mutations within the NOD2/ CARD15 gene contribute to CD susceptibility.
Functional studies suggest that inappropriate responses to bacterial components may alter signaling pathways of the innate immune system, leading to
the development and persistence of intestinal inflammation.
Initiating pathogen?
Infectious?
? Possibly non-pathogenic commensal enteric flora

8. Pathogenesis
The mucosa of CD patients is dominated by Th1 (T helper), which produce interferon-γ and IL-2.
In contrast, UC dominated by Th2 phenotype, which produce transforming growth factor (TGF-) and IL-5.
Activation of Th1 cells produce the down-regulatory cytokines IL-10 and TGF-.

9. Ulcerative colitis – microscopic features
Process is limited to the mucosa and submucosa with deeper layer unaffected
Two major histologic features:
- the crypt architecture of the colon is distorted
- some patients have basal plasma cells and multiple basal lymphoid aggregates

10. Ulcerative colitis
is an inflammatory disease of the large intestine, also called the colon. In ulcerative colitis, the inner lining - or mucosa - of the intestine becomes inflamed and develops ulcers
is often the most severe in the rectal area, which can cause frequent diarrhea.

11. Ulcerative colitis – macroscopic features
40-50% of patients have disease limited to the rectum and rectosigmoid
30-40% of patients have disease extending beyond the sigmoid
20% of patients have a total colitis
Proximal spread occurs in continuity without areas of uninvolved mucosa

12. Ulcerative colitis – macroscopic features
Mucosa is :
- erythematous, has a granular surface that looks like a sand paper
In more severe diseases:
- hemorrhagic, edematous and ulcerated
In fulminant disease a toxic colitis or a toxic megacolon may develop ( wall become very thin and mucosa is severly ulcerated)

13. Ulcerative colitis – clinical presentation
The major symptoms of UC are:
- diarrhea
- rectal bleeding
- tenesmus
- passage of mucus
- crampy abdominal pain

14. Ulcerative colitis – clinical presentation
Patients with proctitis usually pass fresh blood or blood-stained mucus either mixed with stool or streaked onto the surface of normal or hard stool
When the disease extends beyond the rectum, blood is usually mixed with stool or grossly bloody diarrhea may be noted
When the disease is severe, patients pass a liquid stool containing blood, pus, fecal matter
Other symptoms in moderate to severe disease include: anorexia, nausea, vomitting, fever, weight loss

15. Ulcerative colitis - complication
Hemorrhage
Perforation
Stricture
Toxic megacolon (transverse colon with a diameter of more than 5,0 cm to 6,0 cm with loss of haustration)

16. UC – disease presentation
MILD
MODERATE
SEVERE
BOWEL MOVEMENTS
< 4 per day
4-6 per day
>6 per day
BLOOD IN STOOL
small
moderate
Severe
FEVER
none
<37,5°C
> 37,5°C
TACHYCARDIA
<90 mean pulse
>90 mean pulse

17. UC – disease presentation
MILD
MODERATE
SEVERE
ANEMIA
mild
>75%
<75%
SEDIMENTATION RATE
<30mm
>30mm
ENDOSCOPIC APPEARANCE
Erythema, decreased vascular pattern, fine granularity
Marked erythema, coarse granularity, contact bleeding, no ulceration
Spontaneous bleeding, ulceration

18. Crohn’s disease
Crohn's disease differs from ulcerative colitis in the areas of the bowel it involves - it most commonly affects the last part of the small intestine and parts of the large intestine.
Crohn's disease isn't limited to these areas and can attack any part of the digestive tract
Crohn's disease generally tends to involve the entire bowel wall

19. Crohn’s disease – macroscopic features
Can affect any part of GI tract from the mouth to the anus
30-40% of patients have small bowel disease alone
40-55% of patients have both small and large intestines disease
15-25% of patients have colitis alone
In 75% of patients with small intestinal disease the terminal ileum in involved in 90%

20. Distribution of gastrointestinal Crohn's disease.
Based on data from American Gastroenterological Association.

21. Crohn’s disease – macroscopic features
CD is a transmural process
CD is segmental with skip areas in the midst of diseased intestine
In one –third of patients with CD perirectal fistulas, fissures, abscesses, anal stenosis are present

22. Crohn’s disease – macroscopic features
mild disease is characterized by:
aphtous or small superficial ulcerations
In more active disease:
stellate ulcerations fuse longitudinally and transversely to demarcate island of mucosa that are histologically normal
Cobblestone appearance is characteristic of CD (both endoscopically and by barium radiography)

23. Crohn’s disease – macroscopic features
Active CD is characterized by focal inflammation and formation of fistula tracts
The bowel wall thickens and becomes narrowed and fibrotic, leading to chronic, recurrent bowel obstruction

24. Crohn’s disease – macroscopic features
Aphtoid ulceration and focal crypt abscesses with loose aggregation of macrophages which form granulomas
Transmural inflammation that is accompanied by fissures that penetrate deeply into the bowel wall

25. Crohn’s disease – sign and symptoms
Ileocolitis
- right lower quadrant pain and diarhhea
- palpable mass, fever and leucocytosis
- pain is colickly and relieved by defecation
Jejunoileitis
- inflammatory disease is associated with loss of digestive and absorptive surface

26. Crohn’s disease – sign and symptoms
Colitis and perianal disease
- low grade fever, malaise, diarrhea, crampy abdominal pain, sometimes hematochezia
- pain is caused by passage of fecal material through narrowed and inflamed segments of large bowel
Gastroduodenal disease
- nusea, vomiting, epigastric pain
- second portion of duodenum is more commonly involved than the bulb

27. IBD is associated with variety of extraintestinal menifestation.
Almost one-third of the patients have at least one.

28. Extraintestinal manifestation
Dermatologic
1. Erythema nodosum occurs in up to 15% of CD patients and 10% of UC patients
The lesions of EN are hot, red, tender nodules measuring to 5cm in diameter and are found on the anterior surface of the legs, ankles, calves, thighs and arms
2. Pyoderma gangrenosum (PG) is seen in 1 to 12% of UC patients and is less common in CD colitis. PG may occur years before the onset of bowel symptoms.
Lesions are common on the dorsal surface of the feet and legs but may occur on the arms, chest and even face.

29. Extraintestinal manifestation
Rheumatologic
Peripherial arthritis developes in 15 to 20% of IBD patients, is more common in CD.
It is asymmetric, polyarticular and migratory.
Most often affects large joints of the upper and lower extremities
Ankylosing spondylosis (AS) occurs in 10% of IBD.
Sacroilitis is symetrical, occurs equally in UC and CD, often asymptomatic

30. Extraintestinal manifestation
Ocular
The incidence of ocular complications in IBM patients is 1 to 10%
The most common is conjunctivitis, anterior uveitis, episcleritis
Symptoms include: ocular pain, photophobia, blurred vision, headache

31. Extraintestinal manifestation
Urologic
The most frequent genitourinary complications are: calculi, ureteral obstruction, fistulas
The highest frequency of nephrolithiasis (10-20%) occurs in patients with CD.

32. Patients with IBD have an increased prevelance of osteoporosis secondary to vitamin D deficiency, calcium malabsorbtion, malnutrition, corticosteroid use
More common cardiopulmonary manifestations include endocarditis, myocarditis, pleuropericarditis and interstitial lung disease.

33. Different clinical featuresUC
Crohn’s disease
Blood in stool
Yes
Occasionally
Mucus
Systemic symptoms
Frequently
Pain
Abdominal mass
Rarely
Perineal disease No

34. Different clinical featuresUC
Crohn’s disease
Fistulas No
Yes
Small intestine obstruction
Frequently
Colonic obstruction
Rarely
Response to antibiotic
Recurrence after surgery

35. Different endoscopic featuresUC
Crohn’s disease
Rectal sparing
Rarely
Frequently
Continuous disease
Yes
Occasionally
„cobblestoning” No
Granuloma on biopsy