Transcript L3_Ulcerative coliti..

Inflammatory bowel
disease
Inflammatory bowel disease
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refers to two chronic diseases that cause
inflammation of the intestines: ulcerative
colitis and Crohn's disease.
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Although the diseases have some features in
common, there are some important differences.
Inflammatory bowel disease
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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
Inflammatory bowel disease
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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
Epidemiology of IBD
Incidence (US)
Age of onset
Male:female ratio
Smoking
Ulcerative colitis Crohn’s disease
11/100 000
7/100 000
15-30 & 60-80
15-30 & 60-80
1:1
1,1-1,8:1
May prevent
disease
May cause disease
Oral contraceptive No increased risk Relative risk 1,9
Appendectomy
Not protective
Monozygotic twins 8% concordance
Protective
67% concordance
Genetics
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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 20–40fold.
Etiology
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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
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the development and persistence of intestinal inflammation.
Initiating pathogen?
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Infectious?
? Possibly non-pathogenic commensal enteric flora
Pathogenesis
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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 downregulatory cytokines IL-10 and TGF-.
Ulcerative colitis – microscopic features
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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
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Ulcerative colitis
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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
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is often the most severe in the rectal area,
which can cause frequent diarrhea.
Ulcerative colitis – macroscopic features
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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
Ulcerative colitis – macroscopic features
Mucosa is :
- erythematous, has a granular surface that looks like a sand
paper
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In more severe diseases:
- hemorrhagic, edematous and ulcerated
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In fulminant disease a toxic colitis or a toxic megacolon may
develop ( wall become very thin and mucosa is severly
ulcerated)
Ulcerative colitis – clinical presentation
The major symptoms of UC are:
- diarrhea
- rectal bleeding
- tenesmus
- passage of mucus
- crampy abdominal pain
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Ulcerative colitis – clinical presentation
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Patients with proctitis usually pass fresh blood or bloodstained mucus either mixed with stool or streaked onto the
surface of normal or hard stool
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When the disease extends beyond the rectum, blood is usually
mixed with stool or grossly bloody diarrhea may be noted
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When the disease is severe, patients pass a liquid stool
containing blood, pus, fecal matter
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Other symptoms in moderate to severe disease include:
anorexia, nausea, vomitting, fever, weight loss
Ulcerative colitis - complication
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Hemorrhage
Perforation
Stricture
Toxic megacolon (transverse colon with a
diameter of more than 5,0 cm to 6,0 cm with
loss of haustration)
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
none
<90 mean
pulse
>90 mean
pulse
UC – disease presentation
MILD
MODERATE
SEVERE
ANEMIA
mild
>75%
<75%
SEDIMENTATION
RATE
<30mm
>30mm
>30mm
ENDOSCOPIC
APPEARANCE
Erythema,
decreased vascular
pattern, fine
granularity
Marked erythema,
Spontaneous
coarse granularity,
bleeding, ulceration
contact bleeding, no
ulceration
Crohn’s disease
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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.
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Crohn's disease isn't limited to these areas and can
attack any part of the digestive tract
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Crohn's disease generally tends to involve the entire
bowel wall
Crohn’s disease – macroscopic features
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Can affect any part of GI tract from the mouth to the anus
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30-40% of patients have small bowel disease alone
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40-55% of patients have both small and large intestines disease
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15-25% of patients have colitis alone
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In 75% of patients with small intestinal disease the terminal
ileum in involved in 90%
Distribution of gastrointestinal Crohn's disease.
Based on data from American Gastroenterological Association.
Crohn’s disease – macroscopic features
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CD is a transmural process
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CD is segmental with skip areas in the midst of
diseased intestine
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In one –third of patients with CD perirectal fistulas,
fissures, abscesses, anal stenosis are present
Crohn’s disease – macroscopic features
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mild disease is characterized by:
aphtous or small superficial ulcerations
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In more active disease:
stellate ulcerations fuse longitudinally and
transversely to demarcate island of mucosa that are
histologically normal
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Cobblestone appearance is characteristic of CD (both
endoscopically and by barium radiography)
Crohn’s disease – macroscopic features
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Active CD is characterized by focal
inflammation and formation of fistula tracts
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The bowel wall thickens and becomes
narrowed and fibrotic, leading to chronic,
recurrent bowel obstruction
Crohn’s disease – macroscopic features
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Aphtoid ulceration and focal crypt abscesses with
loose aggregation of macrophages which form
granulomas
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Transmural inflammation that is accompanied by
fissures that penetrate deeply into the bowel wall
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
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Jejunoileitis
- inflammatory disease is associated with loss of
digestive and absorptive surface
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Crohn’s disease – sign and symptoms
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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
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Gastroduodenal disease
- nusea, vomiting, epigastric pain
- second portion of duodenum is more commonly involved than
the bulb
IBD is associated with variety of
extraintestinal menifestation.
Almost one-third of the patients have at
least one.
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.
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
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
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.
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.
Different clinical features
UC
Crohn’s disease
Blood in stool
Yes
Occasionally
Mucus
Yes
Occasionally
Systemic
symptoms
Pain
Occasionally
Frequently
Occasionally
Frequently
Abdominal mass Rarely
Yes
Perineal disease
Frequently
No
Different clinical features
UC
Crohn’s disease
Fistulas
No
Yes
Small intestine
obstruction
Colonic
obstruction
Response to
antibiotic
Recurrence after
surgery
No
Frequently
Rarely
Frequently
No
Yes
No
Yes
Different endoscopic features
Rectal sparing
UC
Crohn’s disease
Rarely
Frequently
Continuous
Yes
disease
„cobblestoning” No
Occasionally
Granuloma on
biopsy
Occasionally
No
Yes