1. This document summarizes key information about inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. It discusses their epidemiology, pathogenesis, morphology, and complications. 2. Crohn's disease can involve any part of the gastrointestinal tract and is characterized by transmural inflammation. Ulcerative colitis is limited to the colon and rectum. Both result from an abnormal immune response to intestinal bacteria in a genetically susceptible host. 3. The document also summarizes acute appendicitis, including its causes, pathogenesis, morphology, and complications like perforation. It identifies common tumors of the appendix such as carcinoid tumors and mucinous cystadenocarcinoma.

1. SMALL & LARGE INTESTINE
PATHOLOGY

2. Objectives
• Describe Crohns disease: - epidemiology,
marphology, complications and systemic effect.
• Identify Ulcerative colitis , epidemiology,
morphology, complications and its relation to
cancer.
• Look into the causes and pathogenesis of acute
appendicitis
• Identify common appendicial tumors.

3. Inflammatory Bowel Disease (IBD)
Chronic relapsing inflammatory disorder comprising of
two major entities:
1- Crohn Disease (CD) or Regional Enteritis
Involves any part of GIT
2- Ulcerative Colitis (UC)
Limited to colon and rectum

4. Epidemiology of IBD
• Common in females, frequent in adolescence or in
young adults
• Worldwide IBD incidence rising, due to improved
hygiene and food storage conditions, resulted in
decreased frequency of enteric infections and
inadequate development of regulatory processes that
limit mucosal immune responses early in life (Hygiene
hypothesis )
• Such individuals when exposed to harmless microbes
later in their life triggers inappropriate self-sustaining
immune responses, that increases the risk of
developing IBD

5. PATHOGENESIS of IBD
Epidemiologic, genetic, and clinical studies support
that IBD results from a combination of abnormal host
interactions with intestinal microbiota, intestinal
epithelial dysfunction and aberrant mucosal immune
responses
1. Genetics:
Genes involved in immune responses to intracellular
bacterial products are;NOD2, ATG16 and IRGM, their
mutation plays role only in the pathogenesis of CD

6. PATHOGENESIS of IBD
2. Mucosal immune responses
TH1 and TH17, T cells contribute to
pathogenesis of CD. (IL-23 is
involved in the development
and maintenance of TH17 cells)
In UC the pathogenic immune
response includes increased
mucosal IL-13 production, and
to a lesser degree in CD
Polymorphisms of the IL-10 gene
and its receptor gene, have
been linked to UC but not to
CD, emphasizing importance of
immuno-regulatory signals in
IBD pathogenesis

7. PATHOGENESIS of IBD
3. Epithelial defects
• In a genetically susceptible host, release of TNF and
other immune-mediated signals increases tight junction
permeability, thus increasing transepithelial flux of luminal
bacterial components to mucosal lymphoid tissue –
triggering immune response sufficient to initiate IBD
• Abnormal T-Cell response results in too much T-cell
activation and/or too little control by regulatory T-
lymphocytes results in mucosal damage
• Paneth cell granules, that can affect composition of the
luminal microbiota, are abnormal in patients with CD,
carrying ATG16L1 mutations

8. PATHOGENESIS of IBD
4. Microbiota
• Enormous microbial flora in GIT lumen can be modified
by diet, antibiotics and disease, this can be helpful in
maintenance of remission in CD
• Metronidazole and mixtures containing probiotic, or
beneficial bacteria may combat IBD in some cases
• Other factors associated with IBD for unknown reasons
includes; a single episode of appendicitis reduces risk of
developing UC, smoking increases CD, whereas it
reduces risk of UC

9. Crohn Disease
Gross morphology:
• Mucosa shows skip lesions
• Cobblestone appearance
• Transmural involvement
• Serosal surface Creeping fat
• Early- aphthous ulcers
• Late- linear serpentine ulcer
• Healing→ long rail-track
scars
• Pseudopolyps or mural
bridging lesions
• Stricture, fissure, fistulae
formation
• Mesenteric lymphadenopathy

10. Crohn Disease
MICROSCOPY
• Sharply delimited transmural
chronic inflammation with
lymphoid follicles
• Mucosal ulceration, crypitis,
and crypt abscesses
• Non caseating granulomas in
40-60% of cases
COMPLICATIONS
• Intramural abscess/perforation
• Fistulae and Fissures with
urinary bladder, vagina and
perianal tissue
• Stricture formation

11. Clinical Manifestations
• Intermittent attacks of mild diarrhea, fever and abdominal pain
spaced by asymptomatic periods lasting for weeks to months
• Colonic involvement, results in fecal blood loss
• Extensive involvement of ileum result in marked loss of
albumin- protein losing enteropathy
• Malabsorption of vit B12- Pernicious anemia
• Malabsorption of bile salts –steatorrhea
• Extraintestinal manifesintations includes: migratory
polyarthritis, sacroilitis, ankylosing spondylitis, erythema
nodusum, clubbing of fingers, hepatic primary sclerosing
cholangitis

12. Crohn Disease
Diagnosis of IBD
• Clinical history
• Radiographic- string sign in CD
• Lab Findings (serum antibodies):
- pANCA positive in75%of UC and 11% in CD
- ASCA elevated in CD
• Biopsy

13. Ulcerative Colitis
• Age: 20-30yrs Sex: ♂=♀
• Etiology: unknown
• S/S: prolonged duration, many remissions and exacerbations
• Site: left sided colon, begins in rectosigmoid
• Ulcerative proctitis—disease localized to rectum
• Pancolitis—involve entire colon
• Typhlitis – involve caecum

14. Ulcerative Colitis Morphology
Acute stage:
Mucosa wet and glare
Petechial hemorrhages
Ulcers undermining mucosa,
mucosal bridges
Pseudopolyps
Back wash ileitis
Advanced stage:
Bowel—fibrotic, narrowed
and shortened
Atrophy of wall
Quiescent stage:
No ulceration, mucosa
atrophic

15. Ulcerative Colitis
Microscopy:
Acute (active) stage:
Crypt abscess, cyrptitis, crypt
destruction
Decreased cytoplasmic mucus
Paneth cell metaplasia
Atrophic and regenerative changes in
glands
Ulcers covered by granulation tissue
Pseudopolyps (granulation tissue +
inflamed mucosa)
Quiescent (inactive)stage:
Mucosa grossly normal, mucin restored
Irregularly branched glands,
Scanty Paneth cells and neutrophils

16. Clinical Manifestation of UC
• Relapsing disorder, asymptomatic interval of months
to years
• Attacks of bloody mucoid diarrhea persist for days,
weeks to months
• Initial attack may lead to serious bleeding with fluid
and electrolyte imbalance
• Toxic megacolon may lead to perforation
• Indeterminate colitis; when there is histopathologic
and clinical overlap between UD and CD
• Extraintestinal manifestations: Liver disease,
Arthritis, Uvietis, Pyoderma gangreonosum

17. Colitis-Associated Neoplasia
Long-term complications of UC
and colonic CD is the
development of low to high-
grade dysplasia which is
related to several factors:
•Risk increases sharply 8 to 10
years after disease initiation
•Greater risk in pancolitis
•Greater frequency and severity
of active inflammation may
increase the risk

18. Comparison between UC and CD

19. Acute Appendicitis
Causes of acute appendicitis
Obstructive:
• Fecolith
• Foreign body
• Calculus-gall stone
• Mucocoele
• Tumor: primary secondary--- cecum
• Diffuse lymphoid hyperplasia (10 to 19 yrs)
• Oxyuris vermicularis
Non-obstructive:
• Secondary to generalized infection (e.g TB, Measles)
• Crohn disease

20. Pathogenesis
Associated with obstruction in 50% to 80%
• Continued mucin secretion
• Increase intraluminal pressure
• Compromise venous out flow
• Ischemic injury
• Bacterial proliferation
• Additional inflammatory edema and exudation,
further embarrassing blood supply
In non-obstructive cases pathogenesis is unknown

21. Morphology Acute Appendicitis
Early stage
• Scanty transmural neutrophilic
infiltrate
• Subserosal vessels; congested
• Serosa; dull, granular and
reddish in color
Later stage
• Rich neutrophilic exudate and
fibrinopurulent deposits over
serosa
• Abscess formation, ulcerations
and foci of suppurative necrosis
Histologic criterion for diagnosis
of acute appendicitis is
neutrophlic infiltrate in the
muscularis propria

22. Acute Appendicitis
Complications:
1. Perforation, peritonitis
/appendicular mass
formation
2. Pyelophlebitis
3. Portal vein thrombosis
4. Liver abscess
5. Bacteremia
Differential Diagnosis:
1.Mesenteric lymphadenitis
2.Pelvic bleed in ovulation
3.Acute diverticulitis
4.Meckel’s diverticulitis
5.Ureteric colic
6.Acute Salpingitis

23. Tumors of Appendix
Non-neoplastic:
MUCOSAL HYPERPLASIA
Neoplastic:
MUCINOUS TUMORS
Mucinous cystadenomas
Mucinous cystadenocarcinoma
ADENOCARCINOMA
Primary or secondary
CARCINOID
(Occurs at any age, Incidental finding, Location tip of appendix,
Rarely more than 2cm in diameter, almost uniformly benign)

24. Home Assignment
Q.1. Compare the gross morphological features
of Crohn disease and Ulcerative colitis in a
tabulated form.
Q.2. Enlist morphological types of common
intestinal ulcers.
Note the assignment sholud be hand wrriten

25. Learning outcomes
• Describe Crohn disease, its epidemiology,
aetiology, pathogenesis and morphology
• Define ulcerative colitis and describe its
aetiology, pathogenesis and morphology
• Mention the differences between gross and
microscopic appearance of Crohn disease and
ulcerative colitis
• Learn about acute appendicitis and common
appendicial tumours

26. Reference
• Robbins Basic Pathology9th
Edition by Kumar,
Abbas and Aster
• www.studentconsult.com
• www.webPath.com.