1. INFLAMMATORY BOWEL DISEASE
Moderator – Dr. Poonam Nanwani
Speaker – Dr. Sourabh Mandwariya

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

7. PATHOGENESIS
1. Genetic factors
2. Mucosal immune responses
3. Epithelial defects
4. Microbiota

8. PATHOGENESIS
1. Genetic factors
 More dominant in Crohn‘s disease
 Concordance rate in monozygotic twins
 Crohn's disease – 50 % (Similar regions and with in 2 yr of each
other)
 Ulcerative colitis – 16 %
 Concordance rate in Dizygotic twins – 10 % (Both)
 HLA-DR associated familial predisposition
 HLA-DR2 – Ulcerative colitis

9. PATHOGENESIS
1. Genetic factors
 Crohn's disease
 NOD2 (Nucleotide oligomerization binding domain
2) Gene; Chromosome 16q12
 Regulate immune response – prevent
excessive activation by luminal microbes
 Four fold increase in Crohn's disease risk
 <10% individual with mutation develop disease

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

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

13. PATHOGENESIS
2. Mucosal immune responses
 Activation of mucosal immunity and suppression
of immunoregulation

17. PATHOGENESIS

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

20. PATHOGENESIS
3. Epithelial defects
 Ulcerative colitis
 ECM1 (Extracellular matrix protein 1)
polymorphism
 Inhibition of matrix metalloproteinase 9

21. PATHOGENESIS
4. Microbiota
 Varies between individuals and modified by diet
 Probiotic may combat disease
 Metronidazole and other antibiotics are useful

22. PATHOGENESIS
4. Microbiota
 Implicated causative agent
1. Mycobacterium (Particularly M.
Paratuberculosis)
2. E. Coli
3. Yersinia
4. Streptococcus
5. Viruses (Including measles)

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

32. CROHN'S DISEASE
 Transmural involvement

33. CROHN'S DISEASE
 Cobblestone appearance – Diseased tissue is
depressed below the level of normal mucosa

34. CROHN'S DISEASE
 Gross features
 Cobblestone appearance

35. CROHN'S DISEASE
 Gross features
 Fissures  Fistula tracts  Perforation

36. CROHN'S DISEASE
 Gross features
 Perforation

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

43. CROHN'S DISEASE
 Microscopic features
 Transmural involvement

44. CROHN'S DISEASE
 Microscopic features
 Transmural involvement

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

46. CROHN'S DISEASE
 Microscopic features

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

53. CROHN'S DISEASE
 Clinical features
 Reactivation is associated with
– Emotional stress
- Specific dietary items
- Smoking

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

57. CROHN'S DISEASE
 Clinical features
 Extra intestinal manifestation (25%) –
 Skin involvement - Erythema nodosum
- Perianal abscess and fistula
formation
- Erythema multiforme
- Aphthous ulcer
- Cutaneous vasculitis

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

65. Farmer RG, Easley KA, Ranking GB. Dig Dis
Sci 1993;38(6):1137-1146.
ULCERATIVE COLITIS
37%
46%
17%
Farmer RG, Easley KA, Ranking GB. Dig Dis Sci 1993;38(6):1137-1146

66. ULCERATIVE COLITIS
 Gross features
 Mucosa – Red and granular with petechial
hemorrhages

67. ULCERATIVE COLITIS
 Gross features
 Active disease (left)
atrophic changes(Right)

68. ULCERATIVE COLITIS
 Gross features
 Sharp demarcation between active ulcerative colitis
and normal area

69. ULCERATIVE COLITIS
 Gross features
 Broad based ulcer
with various size

70. ULCERATIVE COLITIS
 Gross features
 Pseudopolyps – Elevated small
multiple sessile reddish nodule
due to isolated islands of
mucosal ulceration

71. ULCERATIVE COLITIS
 Gross features
 Pseudopolyps

72. ULCERATIVE COLITIS
 Gross features
 Pseudopolyps and cobblestone appearance

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

78. ULCERATIVE COLITIS
 Microscopic features
 Mucosal and submucosal
involvement

79. ULCERATIVE COLITIS
 Microscopic features
 Acute phase – Inflammatory cell infiltrate in lamina
propria
 Progressive destruction of glands

80. ULCERATIVE COLITIS
 Microscopic features
 Crypt abscess – Collection of neutrophils in
glandular lumen

81. ULCERATIVE COLITIS
 Microscopic features - Crypt abscess

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,

86. ULCERATIVE COLITIS
 Clinical features
 Extra intestinal manifestations
– Ocular manifestation – Uveitis
- Musculoskeletal system - Migratory polyarthritis
- Ankylosing spondylitis
- Skin lesions - Pyoderma gangrenosus
- Perianal abscess

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

90. LABORATORY INVESTIGATIONS

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

96. IBD ASSOCIATED NEOPLASM
 Indefinite for dysplasia

97. IBD ASSOCIATED NEOPLASM
5. Positive for dysplasia, low grade

98. IBD ASSOCIATED NEOPLASM
6. Positive for dysplasia, high grade

99. IBD ASSOCIATED NEOPLASM

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

109. CROHN'S DISEASE
 Microscopic features
 Fissures

110. THANK YOU

111. THANKS