Gastrointestinal Disease

Inflammatory bowel disease and Appendicitis

Recommended reading – Robbins Basic Pathology

10TH Edition – pp 621-626

Dr Rajani R
Learning objectives

SLO# 1 : Describe the etiopathogenesis, clinical manifestation and method of

diagnosis of Inflammatory bowel diseases

SLO# 2 : Differentiate gross and microscopic findings between Crohn’s

disease and ulcerative colitis

SLO# 3 : list the causes of appendicitis

SLO#4 :Describe the pathogenesis and morphology of acute appendicitis

SLO# 4:List the complications appendicitis

 IDIOPATHIC (CHRONIC) INFLAMMATORY
BOWEL DISEASE

▪Crohn’s disease (CD),

▪Ulcerative colitis (UC)
▪Chronic relapsing inflammatory conditions due to
inappropriate and persistent activation of the
mucosal immune system
▪Developed countries > developing countries
 IDIOPATHIC INFLAMMATORY BOWEL
DISEASE

▪CD – autoimmune, involves esophagus – anus,

more in distal small intestine & colon
▪UC – chronic inflammatory disease limited to colon
and rectum
▪CD and UC – both show extra-intestinal inflammatory
manifestations
 IBD - PATHOGENESIS

Loubna Abdel Hadi, Clara Di Vito, Laura Riboni, "Fostering Inflammatory Bowel Disease: Sphingolipid Strategies to Join Forces", Mediators of Inflammation,
vol. 2016, Article ID 3827684, 13 pages, 2016. https://doi.org/10.1155/2016/3827684
 IBD - PATHOGENESIS

▪Normal GIT – mucosal immune system unresponsive to

normal intestinal microflora but responds against foreign
pathogens
▪In IBD – above homeostasis is disrupted
➢ Abnormal immune response against normal gut flora &
self-antigens – T cells, TNF alpha
(treatment – immunosuppressive, TNF antagonists
➢ Defects in epithelial barrier function
➢ Genetically susceptible people
 PATHOGENESIS
GENETIC SUSCEPTIBILITY
▪ 15% of IBD patients – affected first degree relatives
▪ High incidence in monozygotic twins
▪ HLA associations – HLA –DR1 (CD), HLA-DR2 (UC)
▪ Crohn’s disease - mutations in NOD2 gene (normal NOD2 gene
encodes protein that binds to
bacteria)

↓ activity of the protein

persistence of intracellular microbes

uncontrolled immune responses

 IBD - DIAGNOSIS

❖Clinical

malabsorption
❖Laboratory
diagnosis

❖Radiological

❖Histopathological
diagnosis By anita Afzali – Harborview medical centre
 CROHN DISEASE
EPIDEMIOLOGY
▪Primarily in Western developed countries
▪3-5/100,000 population, peak age – 2nd & 3rd decades
▪F>M
▪Smoking – strong exogenous risk factor
▪GIT manifestations (anywhere from mouth to anus –
especially terminal ileum, ileocecal valve, cecum) +
systemic manifestations
▪Old term - “terminal ileitis” or “regional enteritis”
(abnormal bowel segments with normal “skip” areas)
 Clinical Manifestation
▪ Extremely variable
▪ Some patients it begins with intermittent attacks of
mild diarrhea, fever and abdominal pain.
▪ 20% Acute pain in right lower quadrant pain and fever
– mimic- acute appendicitis / bowel perforation
▪ Colonic involvement – bloody diarrhea
• D/D – Enterocolitis
▪ Waxing and waning – triggered by physical and
emotional stress, specific dietary items, NSAIDS and
smoking.
 CD – COMPLICATIONS
EXTRAINTESTINAL
▪Migratory polyarthritis
▪Ankylosing spondylitis
▪Uveitis
▪Hepatic pericholangitis
▪Increased incidence of cancer of GIT – 5 – 6 X normal
population
▪Cancers with Crohn’s disease are less common than
cancers associated with ulcerative colitis
 CROHN DISEASE
GROSS
▪Small intestine – 40% of
cases,
small intestine + colon –
30%
▪Serosa – granular, dull gray
▪Focal mucosal ulcers
Mucosa – “Cobblestone”appearance
(aphthous ulcers) – join to
form linear serpentine
ulcers, fissures(deep, can
perforate) fistulae, sinuses
▪“Skip lesions”

Linear aphthous ulcers

 CROHN DISEASE
GROSS

▪“Creeping fat” around bowel

▪Intestinal wall – rubbery,
thick (edema, inflammation,
fibrosis)

▪X-ray – “string” sign

appearance
 CROHN DISEASE
MICROSCOPY
▪Mucosal ulcers, neutrophilic
infiltration
▪Crypt abscesses (CA)
LA
▪Transmural inflammation,
CA
lymphoid aggregates (LA) in
bowel wall
▪Noncaseating granulomas (GR)
▪Chronic mucosal damage –
blunting of villi
GR
 CD - COMPLICATIONS
INTESTINAL

▪Fibrosing strictures (terminal ileum - obstruction),

• Fistulae (to bowel, bladder, vagina), sinuses
▪Generalized malabsorption
▪Protein losing enteropathy
▪Malabsorption of vit. B12 - pernicious anemia
▪Steatorrhea – malabsorption of bile salts
 ULCERATIVE COLITIS
EPIDEMIOLOGY

▪Global distribution, more common than Crohn’s

▪Whites > blacks, familial association +
▪Females > males, peak age – 20 – 25 years
▪Extends continuously proximally from rectum,
involves entire colon
▪GIT manifestations + systemic manifestations
 ULCERATIVE COLITIS

Clinical Features

• Relapses and remissions

• Characterized by attacks of bloody diarrhea with
expulsion of stringy, mucoid material and lower
abdominal pain and cramps that are temporarily
relieved by defecation.

• Often, serious bleeding – fluid & electrolyte

imbalances – medical emergency
 ULCERATIVE COLITIS
GROSS

▪Severe pancolitis, no “skip”

lesions
▪Distal ileum involved –
“backwash ileitis”
▪Disease limited to mucosa
& submucosa
▪Red, granular mucosa – later,
ulceration
uninterrupted mucosal inflammation and superficial ulceration
extending from the rectum to the ascending colon.
ULCERATIVE COLITIS
GROSS

▪Islands of regenerating mucosa

pseudo polyps
▪Very severe cases – toxic damage to
nerve plexus & muscularis propria,
swelling, gangrene of colon –
TOXIC MEGACOLON

X-ray – rigid ahaustral

appearance of colon –
lead pipe sign
 ULCERATIVE COLITIS
MICROSCOPY

▪Collections of neutrophils in crypts –

crypt abscesses
▪Later, ulceration of mucosa
▪Healed disease – submucosal
fibrosis, atrophy of
colonic glands
▪Epithelial changes – dysplasia – low
grade to high grade - carcinoma
Atrophic colonic glands
 ULCERATIVE COLITIS
COMPLICATIONS
INTESTINAL
Dysplasia's – infiltrating adeno -
carcinomas in patients with pancolitis
of more than 10 years
EXTRA INTESTINAL MANIFESTATIONS
▪migratory polyarthritis, ankylosing
spondylitis, uveitis, pericholangitis
▪UC + ankylosing spondylitis –
HLA B27
 Comparison of Crohn disease
and ulcerative colitis

CD –involves esophagus – anus,

ilium
more in distal small intestine, colon
UC – chronic inflammatory disease
usually limited to colon and rectum
CD and UC – both show
extra intestinal inflammatory
manifestations
THE APPENDIX
 ACUTE APPENDICITIS

Common cause of acute abdomen

Etiology:
▪Associated with obstruction in 50 – 80 % of cases
fecoliths (hard fecal pellets due to dehydration)
lymphoid hyperplasia (viral infections), tumor,
worms
▪specific inflammations – typhoid, TB, ulcerative
colitis, Crohn’s disease
ACUTE APPENDICITIS
MORPHOLOGY

Gross:
▪Normal glistening serosa – yellow,
hyperemia+ 1
▪later fibrinopurulent reaction over
mucosa
Microscopy:
▪Ulcerated mucosa 2
▪neutrophilic infiltration in
muscularis propria 3
 ACUTE APPENDICITIS
COMPLICATIONS

▪ Inflammation in all layers of appendix – serosal

inflammation – suppurative appendicitis
Edema and exudates in wall of
appendix toxic damage to blood vessels
increased pressure & thrombosis
common complecation

ischemia – gangrenous appendix

– perforation of appendix - peritonitis

▪ Rare – bacteremia, liver abscess