2. INTRODUCTION
Group of inflammatory disorders thought to be
result of inappropriate activation of mucosal
immune system driven by the presence of normal
luminal flora.
Ulcerative Crohn‘s
Two disorders Colitis Disease
1. Crohn‘s disease
2. Ulcerative colitis
INDETERMINATE
COLITIS
3. EPIDEMIOLOGY
Common in Female
Age group – Teens and early 20s
Common in western world
Prevalence increasing in developing nations
4. EPIDEMIOLOGY
Improved food storage
Decreased food contamination
Hygiene Reduced frequency of enteric infection
Hypothes
is Inadequate development of mucosal immune
response regulatory process
Excessive response to self limited diseases
Chronic inflammatory disease
5. EPIDEMIOLOGY
Hygiene hypothesis supported by
Low incidence of IBD in the helminthes
infection prevalent areas
IBD may precedes by an episode of acute
infectious gastroenteritis
6. PATHOGENESIS
Idiopathic Intestinal
Epithelial
disorder Dysfuncti
on
Aberrant Defect in
Mucosal Host
Immune Interaction
Respons with
e Intestinal
Microbiota
10. PATHOGENESIS
NOD2 (Nucleotide oligomerization binding domain
2) Gene
Binds to intracellular bacterial peptidoglycans
Activates NF-kB
In NOD2 Mutation
Luminal microbes are less effectively
recognized
Microbes enter to lamina propria
Trigger inflammatory responses
11.
12. PATHOGENESIS
ATG16L1 (Autophagy-related 16-like) and IRGM
(Immunity-related GTPase M) Gene
Involved in autophagy and clearance of
intracellular bacteria
None of these genes are associated with ulcerative
colitis
18. PATHOGENESIS
Transepitheli
al flux of
luminal
bacterial
components
Activation
Increase
of innate
flux of
and
luminal
adaptive
material
immunity
Increase Secretion of TNF
tight and inflammatory
junction mediator (In
permeabilit genetically
y susceptible Host)
19. PATHOGENESIS
3. Epithelial defects – Critical component
Crohn's disease
Defects in intestinal epithelial tight junction barrier
function
Associated with NOD2 Mutation
Mutation of organic cation transporter SLC22A4
Defect in secreted mucin
21. PATHOGENESIS
4. Microbiota
Varies between individuals and modified by diet
Probiotic may combat disease
Metronidazole and other antibiotics are useful
23. PATHOGENESIS
6. Other Factors
An episode of appendicitis
– Reduce risk of ulcerative colitis
Smoking – Reduces risk of ulcerative colitis
- Increases risk of Crohn's's disease
24. CROHN'S DISEASE
In 850 AD King Alfred, "England's Darling” had a GI
illness that began at age 20 yr
At the time the illness was thought to
be due to punishment for the King's
infidelities. It is now thought to be
Crohn's disease
Louis XIII of France (1601-1643)
25. CROHN'S DISEASE
1913 Dr. Dalziel - Described transmural intestinal
inflammation in 13 autopsied patients.
First fully described and published by
– Crohn's, Ginzburg, Oppenheimer (1932)
Regional enteritis or Granulomatous colitis
26. CROHN'S DISEASE
Equal frequency in both sexes
Common in twenties to thirties
Can manifest in any age from childhood to old age
May occur in any area of GI tract
Most common sites – Terminal ileum
- Iliocecal valve
- Cecum
27. Crohn's’s Disease:
CROHN'S DISEASE
Anatomic Distribution
Small bowel
alone
(33%)
Ileocolic
(45%)
Colon alone
Freq of involvement (20%)
Most Least
28. CROHN'S DISEASE
Gross features
Earliest Crohn's disease lesion – Aphthoid ulcers
Pinpoint reddish
purple erosions
of mucosa
Progress to elongated
serpentine ulcers
29. CROHN'S DISEASE
Gross features
- Sharp demarcation between
normal and abnormal areas
30. CROHN'S DISEASE
Skip lesions – multiple, separate sharply delineated
areas of disease
31. CROHN'S DISEASE
Occasionally entire length of small bowel will be
evolved ( Diffuse jejunoileitis)
Soggy feeling of small bowel
Edema, fibrosis and loss of normal mucosal
architecture
Intramural abscess formation
37. CROHN'S DISEASE
Gross features
Creeping fat – In extensive
transmural disease
extension of mesenteric
fat around the serosal
surface
38. CROHN'S DISEASE
Gross features
Thickened and rubbery
intestinal wall
– Due to transmural edema,
inflammation, submucosal
fibrosis, hypertrophy of
muscularis propria
39. CROHN'S DISEASE
Strictures are common
– Marked narrowing of
lumen along with
dilatation and
hypertrophy of
proximal segment
40. CROHN'S DISEASE
Microscopic features
Submucosal lymphedema – Earliest change
Active disease – Marked infiltration of neutrophils
and destruction of crypt epithelium
Mucosal ulceration, necrosis and atrophy with loss
of crypts
41. CROHN'S DISEASE
Microscopic features
Distortion of mucosal
architecture
– By repeated cycles
of destruction and
regeneration
42. CROHN'S DISEASE
Microscopic features
Lymphoid hyperplasia – Lamina propria and
submucosa
Chronic inflammatory cell infiltrate
Edema, lymphatic dilation, hyperemia along with
hyperplasia of muscularis mucosa
45. CROHN'S DISEASE
Microscopic features
Noncaseating granulomas
Hallmark of Crohn's disease (60% cases)
Sarcoid – like – with in center of lymphoid follicle
Composed of epithelioid cells and multinucleated
giant cells with absent or minimal necrosis
47. CROHN'S DISEASE
Microscopic features
Noncaseating granulomas
– May present anywhere in the wall of bowel, lymph
node, blood vessels (Granulomatous vasculitis)
48. CROHN'S DISEASE
Microscopic features
Fissures – Slit like spaces with sharp edges and
narrow lumina, arranged perpendicularly to the
mucosa and extending
deeply into the
submucosa or even upto
the muscularis externa
49. CROHN'S DISEASE
Microscopic features
Obliterative muscularization
Increase in number of smooth muscle fibers in
submucosa
Stricture formation
Tenascin – Involved in morphogenesis of muscle
tissue and wound healing
Enteritis cystica profunda – Cystically dilated
50. CROHN'S DISEASE
Microscopic features
Disproportionate inflammation – Well defined focus
of inflammatory cells surrounded by noninflamed
and histologically normal mucosa
Mesenteric lymph nodes – May show granuloma
formation
Metastatic Crohn's disease – Formation of
cutaneous granuloma
51. CROHN'S DISEASE
Clinical features
Intermittent attacks of abdominal pain, fever and
mild bloody diarrhea
Mimic acute appendicitis or bowel perforation
Active disease period is interrupted by
asymptomatic periods for weeks to many months
Undulating yet progressive course
52.
53. CROHN'S DISEASE
Clinical features
Reactivation is associated with
– Emotional stress
- Specific dietary items
- Smoking
54.
55. CROHN'S DISEASE
Other associated clinical features
Small bowel disease – Malabsorption
- Sever protein loss
- Hypoalbuminemia
- Vit. B12 deficiency,
Colonic disease - Iron deficiency anemia
56. CROHN'S DISEASE
Clinical features
Extra intestinal manifestation (25%) –
Ocular manifestation – Uveitis
Musculoskeletal system - Migratory polyarthritis
- Osteoporosis
- Ankylosing spondylitis
Skin involvement - Hidradenitis suppurativa
- Clubbing of finger tips
58. CROHN'S DISEASE
Clinical features
Extra intestinal manifestation (25%) –
Hepatobiliary system – Pericolangitis
- Primary sclerosing cholangitis
59. CROHN'S DISEASE
Differential diagnosis
Tuberculosis – Multiple circumferential ulcers
- Caseous necrosis
Sarcidosis - Rarely involve small intestine
- Associated with other systemic features
60. CROHN'S DISEASE
Differential diagnosis
Yersiniosis – Colonies of gram negative bacteria
beneath the ulcers
- Identification of organism in
stool, lymph
node, blood and peritoneal fluid
Eosinophilic enteritis – Peripheral eosinophilia with
61. ULCERATIVE COLITIS
Greek physician Soranus - 130 AD
First officially described by Wilks and Moxon in
1875
Before this discovery, all diarrheal diseases were
believed to be caused by infectious agents and
bacteria
62. ULCERATIVE COLITIS
Severe ulcerating inflammatory disease limited to
colon and rectum
Involves only mucosa and submucosa
Common age group – 20 to 30 yr and 70 to 80 yr
63. ULCERATIVE COLITIS
Gross features
Always involves rectum
Extends proximally in continuous fashion to involve
colon
Limited disease – Ulcerative proctitis
- Ulcerative proctosigmoiditis
- Left sided colitis
- Pancolitis
64. ULCERATIVE COLITIS
Gross features
- Backwash ileitis – Involvement of distal ileum
73. ULCERATIVE COLITIS
Gross features
Mucosal bridges
– Fusion of tips of
Pseudopolyps
74. ULCERATIVE COLITIS
Gross features
Chronic disease – Mucosal atrophy (Flat and
smooth
75. ULCERATIVE COLITIS
Gross features
Submucosal fat deposition
Fibrotic, narrowed and shortened bowel
76. ULCERATIVE COLITIS
Gross features
Toxic megacolon – Due to destruction of muscularis
propria and disturbed
neuromuscular
function due to
inflammation and
inflammatory
mediators - Significant risk of perforation
77. ULCERATIVE COLITIS
Gross features
No stricture formation
No mural thickening
Normal serosal surface
82. ULCERATIVE COLITIS
Microscopic features
Atrophic and regenerative changes present
together
Stromal inflammatory cell infiltrate
83. ULCERATIVE COLITIS
Microscopic features
Pseudopolyps formation - Composed of granulation
tissue mixed with inflamed and hyperemic mucosa
Duplication of muscularis mucosa
Obliterative endarteritis with dilation and
thrombosis of blood vessels
Accumulation of mast cells at the line of
demarcation between normal and abnormal
84. ULCERATIVE COLITIS
Microscopic features
Pseudo pyloric metaplasia
- Presence of gastric antral
appearing glands
85. ULCERATIVE COLITIS
Clinical features
Relapsing and remitting course
Episode of Mucoid bloody diarrhea, lower
abdominal pain and cramp may last for days to
months
Relived by defecation
Triggering factors – Infectious enteritis,
87. ULCERATIVE COLITIS
Clinical features
Extra intestinal manifestations
– Hepatobiliary system - Fatty infiltration
- Liver abscess
- Cirrhosis
- Pericolangitis
- Primary sclerosing cholangitis
- Carcinoma of biliary tract
88. ULCERATIVE COLITIS
Differential diagnosis
Nonspecific bacterial colitis – Acute inflammation
out
of proportion of chronic inflammation
- Absence of crypt distortion
Allergic colitis and proctitis – Mucosal edema and
eosinophilic infiltration
- Common in infants and children
89. ULCERATIVE COLITIS
Differential diagnosis
Pseudomembranous colitis – Presence of yellow
white
mucosal plaques
- Focal explosive mucosal lesion
Cytomegalovirus colitis – inclusion bodies
- Common in immunocompromised patient
91. SEROLOGICAL STUDIES
Anti - neutrophil cytoplasmic antibodies
– Ulcerative colitis (75% cases)
- Crohn's disease (11% cases)
Anti Saccharomyces cerevisiae antibodies
- IgA and IgG against cell wall of Sac.
cerevisiae – Crohn's disease (60% cases)
92. SEROLOGICAL STUDIES
Anti-OmpC*
Anti-Cbir1
Anti-I2
Anti-Glycan Abs
Anti pancreatic Ab (PAB)
Anti-laminaribocide Ab (ALCA)
Anti-chitobioside (ACCA)
93. INDETERMINATE COLITIS
Definitive diagnosis is not possible in 10 % of cases
Pathological and clinical overlap between
Ulcerative colitis and Crohn's disease
Colonic disease in contentious pattern –
Suggestive of ulcerative colitis
Patchy histological disease, fissure, family history
of Crohn's disease, onset after initiating use of
cigarette – Against Ulcerative colitis
94. IBD ASSOCIATED NEOPLASM
Long term complication
Risk factors
Risk increase after 8 to 10 years of disease
initiation
Patient with Pancolitis are at greater risk
Greater frequency and severity of active
inflammation – increase risk (presence of
neutrophils)
95. IBD ASSOCIATED NEOPLASM
Begins with dysplasia and develop into invasive
carcinomas
Categories for dysplasia
1. Negative for dysplasia
2. Indefinite for dysplasia, probably negative
3. Indefinite for dysplasia, unknown
4. Indefinite for dysplasia, probably positive
100. IBD ASSOCIATED NEOPLASM
Adenocarcinoma
Carcinoid tumor
Anaplastic carcinomas
Carcinosarcomas
Malignant lymphomas
Colonic adenomas may also occur
Regular follow-up with mucosal biopsy
101. TREATMENT
Medical – Immunosuppression
- Elemental diet
- Total parenteral nutrition
Surgical management – Resection of involved
bowel segment
102. CROHN'S DISEASE V/S ULCERATIVE COLITIS
Features Crohn's disease Ulcerative colitis
Clinical
Rectal bleeding Inconspicuous Common
Perforation 4% 12%
Colon carcinomaVery rare 5%-10%
Anal 75 %; Fissure, Rare; Minor
complications Fistulas,
Ulceration
Abdominal mass 10%-15% Practically never
Abdominal pain Usually right- Usually left side
sided
103. CROHN'S DISEASE V/S ULCERATIVE COLITIS
Features Crohn's disease Ulcerative colitis
Radiographic
Sparing of 90 % Exceptional
rectum
Involvement of Common; Rare; Dilated
ileum Constricted (Backwash ileitis)
Strictures Often present Absent
Skip areas Common Absent
Internal fistulas May be present Absent
Longitudinal and Common Exceptional
transverse ulcer
104. CROHN'S DISEASE V/S ULCERATIVE COLITIS
Features Crohn's disease Ulcerative colitis
Morphologic
Distribution of Transmural Mucosal and
involvement submucosal
Mucosal atrophy Minimal Marked
and regeneration
Cytoplasmic Preserved Diminish
mucin
Lymphoid Common Rare
aggregates
Edema Marked Minimal
105. CROHN'S DISEASE V/S ULCERATIVE COLITIS
Features Crohn's disease Ulcerative colitis
Morphologic
Hyperemia Minimal May be extreme
Crypt abscesses Rare Common
Rectal 50 % Practically
involvement always
Granulomas Present in 60% Absent
Fissuring Present Absent
Lymph nodes May contain Reactive
granulomas hyperplasia
106. REFERENCES
Rosai and Ackerman’s; surgical pathology
Robbins and Cotran: pathological Basis of Disease
An atlas of gross pathology; C D M Fletcher & P H
McKee
New Concepts in the Pathophysiology of Inflammatory
Bowel Disease ; Annals of Internal Medicine
Harsh Mohan ; Textbook of Pathology
Various internet link
ASCA:Sacch=brewer’s yeastSimple ELISA, standardized, easy to runPoor correlation with mucosal S. cerevesiaeMallant-Hent RC, et al. World J Gastroenterol 2006;12:292 ANCA:ANCA IgG, pANCA IIF, DNASE senspANCA IIFResults variable based on assay, personnel experience. ELISA+IFE--?60%, IFE alone0-40%