Non neoplastic lesions of intestine

SMALL & LARGE
INTESTINE
PATHOLOGY
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Part 1
Major Causes of Intestinal Obstruction
Mechanical Obstruction
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Adhesions
Hernias
Volvulus
Intussusception
Tumors
Inflammatory strictures
Obstructive gallstones, fecaliths, foreign bodies
Congenital strictures; atresias
Congenital bands
Parasites
Imperforate anus
Pseudo-obstruction
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Paralytic ileus (e.g., postoperative)
Vascular—bowel infarction
Myopathies and neuropathies (e.g., Hirschsprung)
Clinical features
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Abdominal pain
Distension
Vomiting
Constipation
Ischemic Bowel Disease
Acute occlusion of celiac, superior and inferior mesenteric arteries
Chronic hypoperfusion
Types
 Mucosal- acute or chronic hypoperfusion
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Mural- acute or chronic hypoperfusion
Transmural- acute vascular obstruction
Ischemic injury two phases
 Initial hypoxic injury
 Secondary reperfusion injury-generation of
oxygen free radicals, neutrophilic infiltration,
production of inflammatory mediators
Predisposing conditions for ischemia
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Arterial Thrombosis- atherosclerosis, vasculitis
Arterial Embolism-cardiac vegetations
Venous Thrombosis-Oral contraceptives,
postoperative state
Non occlusive ischemia- cardiac failure, shock,
dehydration
Miscellaneous-radiation injury, Diabetes mellitus
morphology
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Gross
Thick, rubbery, edematous wall, dusky to purple red
Mucosa ulcerated & haemmorhagic
Perforation may be present
Microscopic
Atrophic surface epithelium
Neutrophilic infiltration
Fibrous scarring of lamina properia in chronic ischemia
Clinical features
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Sudden severe abdominal
pain
Nausea, vomiting
Bloody diarrhoea,
melanotic stools
Peristaltic sounds
disappear
INFARCTION
INFARCTION
Normal Small Intestine
Malabsorption & Diarrhoea
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Diarrhoea; increase in stool mass, frequency or
fluidity , typically more than 200gm per day
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Secretory diarrhoea
Osmotic diarrhoea
Malabsorptive diarrhoea
Exudative diarrhoea
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CELIAC DISEASE
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Celiac disease (celiac sprue, gluten-sensitive enteropathy) is
an immune mediated enteropathy which improves on
withdrawal of gluten from diet
Celiac disease occurs largely in Caucasians
Pathogenesis
Sensitivity to gluten & alcohol-soluble gliadin (protein found in gluten fraction of wheat) and closely
related grains (oat, barley, and rye)
Interplay between genetic predisposing factors, host immune response, and
environmental factors is central to disease pathogenesis
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Exposure to gliadin results in T-cell mediated chronic inflammatory reaction with
accumulation of intraepithelial CD8+ T cells
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Epithelial cells are induced by gliadin peptides to secrete large amount of IL 15 that
activate CD8+ T cells (increases risk of T cell lymphoma)
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Family history important in celiac disease, almost all individuals with celiac disease
share major histocompatibility complex class II HLA-DQ2 or HLA-DQ8 haplotype
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Proposed that gliadin is deamidated by enzyme transglutaminase into peptides which
binds to DQ2 and DQ8, recognition of these peptides by CD4+ T cells leads `to
secretion of cytokines which damages intestinal epithelium
B cell activation leads to anti-gliadin, anti endomysium and antitransglutaminase Abs
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CELIAC DISEASE
Biopsy second part of duodenum, jejunum
Microscopy:
Villous atrophy
 Crypt elongation, hyperplasia
 Increase mitoses
 Increase in no of lymphocytes, plasma cells,
eosinophils, macrophages
 Intraepithelial leucocytes
 Vacuolar degeneration and loss of brush borders
of surface epithelium
Celiac Disease
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Enteropathy associated T-cell lymphoma
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Small intestine adenocarcinoma
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Dermatitis herpitiformis blistering skin lesion
Diagnosis of Celiac Disease
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Clinical malabsorption (Diarrhea ,flatulence, wt
loss, fatigue, failure to thrive in childern
Small bowel biopsy Villous atrophy
Responds to gluten with drawl
Antigliadin & antiendomysial antibodies
Antitransglutaminase IgA, IgG
Normal/Celiac
Celiac
TROPICAL SPRUE
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Definite geographic distribution
Bacterial etiology : Cyclospora, enterotoxigenic bacteria
Unaffected by gluten ingestion, responds to folic acid,
Vit B12, tetracycline.
Partial villous atrophy
Malabsorption Syndromes
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Autoimmune enteropathy; X linked,
autoantibodies to enterocytes and goblet cells
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Lactase deficiency; congenital or acquired
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Abetalipoproteinemia; chylomicrons are not
assembled, failure to absorb essential fatty acids,
deficiency of fat soluble vitamins
INFECTIOUS ENTEROCOLITIS
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CHOLERA
CAMPYLOBACTER
SHIGELLOSIS
SALMONELLOSIS
TYPHOID FEVER
YERSINIA
E.COLI
PSEUDOMEMBRANOUS ENTEROCOLITIS
VIRAL ENTEROCOLITIS
PARASITIC ENTEROCOLITIS
WHIPPLE’S DISEASE
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Foamy macrophages in lamina properia, villous
expansion, alternating with empty spaces.
Histiocytes cytoplasm contains diastase-resistant PAS
positive lysosomes & gram positive abundant bacilli
Tropheryma whippelii
Bacteria laden macrophages in mesenteric lymph nodes,
synovial membranes of joints, cardiac valves & brain
Diagnosis by PCR, immuno, electron microscopy
DIRRHOA, WEIGHT LOSS, MALABSORPTION
George Hoyt Whipple
noble prize on PA
WHIPPLE
AMOEBIC COLITIS
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Simulate ulcerative colitis or Crohn disease
Gross: ulceration covered by exudate, with normal
intervening mucosa
Site: cecum and ascending colon
L/M: nonspecific
Flask shaped ulcer, relative paucity of inflammatory
cells beneath ulcer
Trophozoites of E. histolytica
Erythrocytosis by trophozoites usually present
Can be detected by PAS stain
Stool R/E
Ameba
Ulcers of Intestine
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OvalSalmonella typhi along axes of ileum
Linear- Salmonella paratyphi
Flask shaped amebic
Irregular – Shigella
Multiple superficial ulcers-Campylobacter jejuni
Ulcer along transverse axes- Tuberculosis
Deep knife like-Crohn
Superficial broad based– Ulcerative colitis
Solitary Rectal Ulcer
Malignant ulcers
Granulomatous lesions of Intestine
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Tuberculosis caseating granulomas
Crohn disease non-caseating granulomas
Foreigen body granulomas
Necrotizing granulomas-Yersinia enterocolitica,
Y. pseudetuberculosis
Oleogranuloma-against fat
SOLITARY RECTAL ULCER
Solitary ulcerated lesion 4-18cm from anal margin
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Associated with rectal prolapse
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S/S: passage of blood and mucus , altered bowel habits
and pain
L/M: superficial and irregular mucosal ulceration
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Hyperplasia of crypts, villous configuration
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Obliteration of lamina propria by fibroblasts, elastin and
smooth muscles
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Thickened muscularis mucosae
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↓ lymphocytes and plasma cells
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Chronic form– similar to colitis cystica profunda
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PART 2
HIRSCHSPRUNG DISEASE
Absent parasympathetic ganglion cells in
intramural and submucosal plexus due to
failure of migration of neural crest cells or
premature death of ganglion cells
 Age: 1st yr life, males
 RET mutations
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P/C: abdominal distention, delayed passage
of meconium, tight anus
 Proximal bowel dilatation & hypertrophy of
muscle
 Complications: acute intestinal obstruction,
enterocolitis, megacolon, perforation, sepsis
HIRSCHSPRUNG’S DISEASE
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Suction biopsy
Intraoperative transmural biopsy
Acquired Megacolon
Chagas disease
Intestinal obstruction by inflammation or tumour
Toxic Megacolon
Normal / Inflamed Appendix
Pathogenesis Acute Appendicitis
Obstruction in 50% to 80% of cases, usually in the form
of a fecalith , less commonly, a gallstone, tumor, or ball
of worms (oxyuriasis vermicularis).
Continued secretion of mucinous fluid in the obstructed
viscus leads to a progressive increase in intraluminal
pressure & causes eventual collapse of the veins
Ischemic injury then favors bacterial proliferation
with additional inflammatory edema and exudation,
further embarrassing the blood supply.
significant minority of inflamed appendices have
no demonstrable luminal obstruction, and the
pathogenesis of the inflammation remains
unknown.
Acute Appendicitis
Morphology:
 Earliest stages, scant neutrophilic exudate in mucosa, submucosa, and
muscularis propria. Subserosal vessels congested, and often perivascular
neurophilic infiltrate. Normal glistening serosa changes into dull, granular,
erythematous surface
 Later stage, a prominent neutrophilic exudate generates a fibrinopurulent
reaction over the serosa , abscess formation within wall, along with ulcerations
and foci of suppurative necrosis in mucosa acute suppurative appendicitis.
 Large areas of hemorrhagic ulceration of mucosa and green-black gangrenous
necrosis of wall, extending to serosa, creating acute
gangrenous appendicitis, followed by rupture and suppurative peritonitis
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The histologic criterion for the diagnosis of acute appendicitis is neutrophilic
infiltration of the muscularis propria.
Acute Appendicitis
ACUTE APPENDICITIS
OBSTRUCTIVE
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fecolith
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foreign body
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calculus-gall stone
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Mucocoele
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Tumor: primary , secondary--- cecum
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Diffuse lymphoid hyperplasia (10 to 19 yrs)
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Oxyuris vermicularis
NON OBSTRUCTIVE
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Secondary to generalized infection (viral-Measles)
Acute Appendicitis
ACUTE APPENDICITIS
D/D
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Mesenteric lymphadenitis
Gynecologic lesions
Acute diverticulitis
Meckel’s diverticulitis
Infarction of greater omentum
Ureteric colic
Chemotherapy induced typhilitis
Tumors of Appendix
Non-neoplastic:
MUCOSAL HYPERPLASIA
Neoplastic:
MUCINOUS TUMORS
Mucinous cystadenomas
Mucinous cystadenocarcinoma
ADENOCARCINOMA
Primary
secondary
CARCINOID
CARCINOID
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Most common tumor of appendix
One in 300 appendicectomies
Peak incidence in 3rd and 4th decades of life
Mostly incidental
Mostly occur at the tip
2 to 3 cm in diameter
GROSS
Firm, grayish white
Fairly well circumscribed
Not encapsulated
Characteristic yellow coloration after
formalin fixation.
Histologic Pattern of Carcinoid
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Classic insular type
Carcinoids with glandular differentiation
Tubular type
Goblet cell carcinoid
IMMUNOHISTOCHEMISTRY
Tumor cells are positive for:
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argentaffin
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argyrophil
Ultrastructurally: filled with pleomorphic dense core
granules
Immunohistochemically reactive for:
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neuron-specific enolase,
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chromogranin
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5-HT
secretory
Diverticulosis
MECKEL’S DIVERTICULUM
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Part 3
Inflammatory Bowel Disease
Chronic condition resulting from inappropriate mucosal
immune activation
 Crohn disease
affect any part of GIT
 Ulcerative colitis
Chronic inflammatory disease limited to colon & rectum
Both exhibit extra-intestinal inflammatory manifestations
Etiology-Pathogenesis
Idiopathic- not an autoimmune
Defect in host interactions with;
Intestinal microbiota
Intestinal epithelial dysfunction
Abberant mucosal immune response
Pathogenesis of IBD
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CD monozygotic twins 50%
UC monozygotic twins 16%
Defective NOD2 signaling
NOD2
NOD2 protein
Binds to intracellular bacterial peptidoglycan & activates
NF-kB (nuclear factor kappa light chain enhancer of
activated B cells )
Defective NOD2 less effective in combating microbes
which enter lamina properia
Pathogenesis of IBD
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Two Crohn Disease related genes are
ATG16L1( autophagy related 16 like)
IGRM 9 ( immuniy related GTPase M )
Pathogenesis of IBD
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Mucosal immune response; role of T cells
Epithelial defects; defects in epithelial tight
junctions, defective transepithelial transport,
defect in mucin barrier, defective epithelial
antibacterial peptides called defensins
Microbiota
Diagnosis of IBD
Clinical history
 Radiographic- string sign in CD
 Lab Findings (serum antibodies):
 pANCA positive in75%of UC & 11%in CD
 ASCA Elevated in CD
 Tissue Diagnosis
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CROHN DISEASE
EPIDEMIOLOGY
 Both sexes female more than males
 All ages peak age 2nd &3rd decade
 Primarily disease of Western developed populations
 Annual incidence in USA 3per 100,000
Fully developed CD is pathologically characterized by;
1. Sharply delimited, transmural inflammatory process with
mucosal damage
2. Non-caseating granulomas
3. Fissures and fistulae
GROSS
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Skip lesions
Cobblestone appearance
Transmural involvement, Creeping fat
Early- aphthous ulcers
Late-Ulcer linear, serpentine
Healing→ scars
Pseudopolyps or mural bridging lesions
Stricture, fissure, fistulas
Mesenteric lymphadenopathy
Metastatic Crohn disease
Terminal ileum, ileocaecal valve, cecum
Crohn disease
Crohn- Cobble Stone &
Sharp Demarcation
CROHN DISEASE
CROHN FISSURE
C/F of CD
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Intermittent attacks of mild diarrhea, fever pain
Attacks precipitated by stress
Colonic involvement ,fecal blood loss, Fe def anemia
Sometime present as a case of acute appendicitis or acute
bowel perforation
Extensive involvement of ileum result in marked loss of
albumin- protein losing enteropathy
Malabsorption of Vit B12
Malabsorption of bile salts –steatorrhea
Fistulae and Fissures with urinarry bladder, vagina,
perianal skin
Extraintestinal manifesintations migratory polyarthritis,
sacroilitis, ankylosing spondylitis, erythema nodusum
clubbing of fingers, primary sclerosing cholangitis
ULCERATIVE COLITIS
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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
Backwash ileitis
ULCERATIVE COLITIS
Gross: varies with stage
 Acute: mucosal surface red and granular
 Petechial hemorrhages
 Broad based ulcers , Pseudopolyps
 Mucosal bridges
 Advanced:
 Mucosal atrophy
 Serosa normal, no stricture, no mural
thickening
 Quiescent: no ulceration, mucosa atrophic
ULCERATIVE COLITIS
ULCERATIVE COLITIS
L/M: mucosal and superficial submucosal disease
 Acute: ↑ inflammatory cells in lamina propria
 Inflammation remain above muscularis mucosae
 Crypt abscess, cyrptitis
 Marked ↓ cytoplasmic mucus, irregularly shaped glands,
paneth cell metaplasia
 Atrophic and regenerative changes in glands
 Nuclear enlargement, ↑ mitosis
 Dilated blood vessels, mucosal capillary thrombi
 Ulcers covered by granulation tissue
 Pseudopolyps= granulation tissue + inflammed mucosa
ULCERATIVE COLITIS
Quiescent stage:
Mucosal atrophy,submucosal fibrosis
Mucin content restored, irregularly branched
glands, paneth cells, neutrophils in lamina
propria
ULCERATIVE COLITIS
Extraintestinal manifestations:
Pericolangitis, Arthritis, Uvietis
Pyoderma gangreonosum
Complications:
perforation, peritonitis, abscess, toxic megacolon,
venous thrombosis
Increase risk of dysplasia/carcinoma
Clinical Manifestation Of UC
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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
Ulcerative Colitis
Dysplasia in Ulcerative colitis
Erythema nodosom
Feature
Macroscopic
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Bowel region
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Distribution
Stricture
Wall appearance
Crohn Disease-Colon
Ulcerative Colitis
Colon ± ileum
Skip lesions
yes
Thick
Colon only
Diffuse
rare
Thin
Microscopic
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Inflammation
Pseudopolyps
Transmural
moderate
Limited to mucosa
Marked
Ulcers
Lymphoid reaction
Fibrosis
Serositis
Granulomas
Fistulae/sinuses
Deep, linear
Marked
marked
marked
Yes (35%)
Yes
Superficial
moderate
Mild to none
Mild to none
No
No
Clinical
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Fat/vit malabsorp
Malignant potential
Recrrence after surgery
Yes, if ileum
+/common
No
Yes
no