Download NOTE: All IBD patients must be routinely monitored for

Lecturer: Ashlie L. Burkart
Lecture: 3
“Bread and Butter” Pathology of the Small Bowel
and Colon
SMALL INTESTINE
A. NORMAL HISTOLOGY OF THE SMALL INTESTINAL
* Mucosa = the epithelium, lamina propria and muscularis mucosae.
o Below the mucosa is the submucosa, muscularis propria, subserosal fat, the serosa or adventita depending on
where in the GI tract you are.
I. Major features
o Plicae circulares: wave like projections formed by
the mucosa and submucosa.
o Villi: smaller undulations formed by only the mucosa
o Crypts of lieberkuhn: crypt-like glands that extend
into the mucosa between the villi.
* Normal intestinal mucosa should have a villi
height : crypt depth of  3:1.
o A microvilli brush border along the epithelium.
o Dispersed goblet cells.
o Intraepithelial lymphocytes (EILs) dispersed
throughout the epithelium.
Normal = < 20 IEL / 100 enterocytes
Normal = decrescendo pattern such that the
IEL are less abundant near the tops of villi.
o Lamina propria should have a normal, mild, mix of
lymphocytes, plasma cells and some eosinophils.
o Brunner’s Glands: Specific to the duodenum!
Glands found below the muscularis mucosae.
Produce an alkaline substance to help neutralize
stomach acid.
o Peyer’s Patches: Specific to the terminal Ilieum.
Lymphoid aggregates that traverse the Muscularis
mucosae.
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Lecturer: Ashlie L. Burkart
Lecture: 3
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B. CELIAC DISEASE (CD)
I. General
o Immune disorder d/t “gluten” sensitivity, or sensitivity to other proteins that resemble gluten.
o Much like an allergic reaction in the intestine.
II. Pathogenesis
o Gluten and related proteins are digested in the small intestine
 gliadin peptide and a tissue transglutaminase (tTG)
modified gliadin protein are formed  reaction to these
proteins especially effects the proximal small intestine.
III. Gross
o Scalloping of mucosa w/ loss of plicae circularis.
IV. Histology
o Biopsy best preformed in duodenum/proximal ilieum where
concentration of gluten is highest.
o Increased IEL cells with loss of “decrescendo” pattern.
o Blunted villi w/ crypt elongation. Villi:Crypt ratio < 3:1
o Increased plasma cells and lymphocytes in lamina propria.
* NOTE: histology is not specific to CD, must be
corroborated with serology testing.
V. Serologic Tests
1. Anti-tTG IgA:
* Best screening test! Cheapest, least labor
intensive, sensitivity and specificity = 90%
2. Serum IgA levels:
o Must test serum IgA levels in general to ensure
there is no IgA deficiency which may give
false negative.
3. Other Serologic Testing:
 Anti-endomysial IgA:
o Just as good as the Anti-tTG IgA test except
more labor intensive.
 Anti-gliadin:
o NOT sensitive or specific but may be used to
follow up response to gluten free diet.
VI. HLA testing of DQ2 and DQ8
* Almost all pts with CD carry the MHC class II
HLA-DQ2 or HLA-DQ8 alleles!!
o Not a good screening test since 20% of the population carry these alleles. But may be useful in diagnosing
when other tests are not sufficient and you have a strong clinical suspicion.
VII. GOLD STANDARD DIAGNOSIS AND TREATMENT
* Gold standard Diagnosis: response to a gluten free diet.
* Treatment: lifelong gluten free diet.
VIII. Diseases that may mimic CD
* Remember the histologic findings are NOT specific to CD, other conditions may have similar features:
1. Common Variable immunodeficiency (CVID): “acquired hypogammaglobinemia”
o Result in villous blunting and increased IEL.
o HOWEVER, most patients have very few (if any) plasma cells in the mucosa whereas in CD there is an elevated
amount of plasma cells.
2. Infections
o H. pylori gastritis, tropical sprue, bacterial overgrowth, viral gastroenteritis, giardia, cryptosporidium, cyclospora.
3. NSAID injury
IX. Disease associated with CD
o Dermatitis herpetiforme: Chronic blistering skin disease associated with a gluten allergy and CD.
David Reilly
Lecturer: Ashlie L. Burkart
Lecture: 3
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o Enteropathy-associated T-Cell lymphoma
At much higher risk for this. Very aggressive.
o Adenocarcinoma of the small intestine.
COLON
A. NORMAL HISTOLOGY OF THE COLON
o Villi create a “test tubes in a rack” appearance where the bases of the intervening crypts touch the Muscularis
mucosae.
o Paneth cells are normally found in the RIGHT colon only!
o Haustrau folds are unique to the colon
o Other wise the histology is very similar to small intestine with lymphocytic presence in the mucosa, etc.
B. MICROSCOPIC COLITIS
I. General Features
* Incorporates lymphocytic and collagenous colitis
o Chronic watery (non-bloody) diarrhea with a normal
endoscopic evaluation.
o Cause usually unknown.
o Typically in middle age  elderly.
* Both have no changes in mucosal architecture!!
II. Lymphocytic Colitis
o Female:male ratio of 3:1
o Increased IEL presence.
o Increased presence of lymphocytes, plasma cells and
eosinophils in the lamina propria.
III. Collagenous colitis
o F:M ratio of 8:1
o Increased IEL presence.
o Increased presence of lymphocytes, plasma cells and
eosinophils in the lamina propria.
* Thickened subepithelial collagen band!!!
C. INFLAMMATORY BOWEL DISEASE (IBD)
 Consists of 3 main subtypes:
o Ulcerative Colitis (UC)
o Crohn’s Disease
o Indeterminate
I. General Features of IBD***
1. Chronicity (chronic changes)
o 1) Architectural distortion:
In Colon: crypts pull away from the MM, have unusual appearance- “pant leg” appearance.
In Small Intestine: villi shortening, crypt elongation.
o 2) Muscularis Hypertrophy and hyperplasia: Muscularis mucosa layer becomes hyperplastic and large.
o 3) Metaplasia of cells: Cell types change, usually in an attempt to adapt to the new environment.
Paneth cell metaplasia of the LEFT colon: Ulcerative Colitis!
Normally paneth cells (antimicrobial, eosinophilic cells with
granules that face TOWARD the lumen) are only found in the right
colon. If found in the Left colon this is metaplasia and is highly
suggestive of IBD.
Pyloric Metaplasia: Crohn’s Disease! generation of glands that
look similar to the pyloric glands of the stomach in the distal ileum.
2. Activity (acute inflammation)
o 1) Cryptitis: neutrophils in the epithelium of crypts
o 2) Crypt abscess: neutrophils accumulate in the lumen of crypts.
II. Changes Specific to Ulcerative Colitis (UC)
1. Gross findings
David Reilly
Lecturer: Ashlie L. Burkart
Lecture: 3
o Starts in the rectum and progresses continuously toward the right colon with NO breaks or patches!
o Inflammatory polyps are common
o Lead pipe colon: loss of haustral folds
o Toxic megacolon: in severe cases of UC neural control is lost and the colon dilates.
2. Microscopic findings
* Disease is LIMITED TO THE MUCOSA!!!!
* Findings of Chronicity and activity esp. those related to colonic location.
III. Changes Specific to Crohn Disease
1. Gross Findings
o Distribution is patchy, most commonly involving the terminal ileum, but also has
patchy distribution throughout the colon and even up to the stomach. Affects any
part of the columnar GI tract.
o Long Linear “Bear Claw like” ulcers
o Cobblestone mucosa: long linear ulcers cross-hatched by normal plicae circularis
* Strictures: d/t muscularis mucosae hypertrophy and hyperplasia.
NOTE: strictures in an IBD patient is Crohn’s until proven otherwise.
2. Microscopic findings
* Inflammatory changes involve THE ENTIRE WALL OF BOWEL!!
o Knife like fissures cut into the mucosa
o Granulomas are often found with multinucleated giant cells.
o Combing fat: serosal/adventitial fat forms comb like projections
into outer layers.
o Lymphoid aggregates are common throughout the width of the
entire wall.
NOTE: All IBD patients must be routinely monitored for
adenocarcinoma, dysplastic changes and malignancy. Risk is
greatly increased even if IBD has resolved.
IV. Algorithm for evaluating IBD
1. Look for features of “chronic” mucosal injury
o Architectural distortion
o Metaplasia: Pyloric metaplasia of terminal ileum or Paneth cell
metaplasia of the left colon.
o Hypertrophy/hyperplasia of MM.
2. Look for features of “activity”
o Neutrophils in crypts or in crypt epithelium
3. Describe the disease distribution
o Primarily involve the terminal ileum with patchy skip lesions:
Crohn’s
o Primarily involves the rectum and progresses proximal
continuously: UC
4. Are there strictures?
o Strictures in IBD are Crohn’s until proven otherwise. Strictures
are only seen in UC with malignancy.
5. Does the process involve the mucosal layer only or the entire wall thickness?
o Also identify classic histo. Features of the disease.
6. Follow up for dysplasia or signs of malignancy
D. ACUTE SELF LIMITING COLITIS
I. General
o Transient, colitis with diarrhea (often bloody)
o Common association: Bacterial enterocolitis
o Usually not biopsied since diagnosis can be made clinically based on stool tests, etc…
o If biopsy is taken, is used to rule out IBD:
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Lecturer: Ashlie L. Burkart
Lecture: 3
* Will have features of acute inflammation (“activity”) but no features of “chronicity”
E. C. DIFFICILE COLITIS
I. General
o Usually follows antibiotic exposure.
o “pseudomembranous colitis”: pseudomembrane of fibrin, mucin and neutrophils covering the mucosa.
Although it is classic of C. Difficile colitis it is NOT diagnostic (ischemia also has a pseudomembrane)
* Defining feature is the dissolution of epithelial cells into the lumen d/t toxin produced by C. dif causing
adhesion of cells to fail.
F. ISCHEMIC BOWEL DISEASE
I. Causes
o Arterial occlusion: usually results in transmural infarction involving entire width of intestinal wall.
o Occlusion of mesenteric veins: back up of deoxygenated blood ischemia
o Luminal insult: pressure in lumen can blanche the mucosa reducing blood flow.
o Non-occlusive ischemia: Hypoperfusion to bowel, possibly d/t shock  results in mucosal ischemia.
II. Pathogenesis
o The mucosa gets blood last and is thus must sensitive to any decrease in blood flow or reduction in
oxygenation.
o Severity of ischemia determines how much of the intestine will be effected.
III. Histology/types
o Mucosal Ischemia: Hyalinization of the lamina propria (looks extra pink), withered crypts, may have
pseudomembrane. Must distinguish from C. Dif colitis.
**epithelial cells will not be falling off into the lumen as in C. Difficile colitis.
o Mural infarct: damage to mucosa and submucosa
o Transmural infarct: damage to entire width of wall. Most often d/t atherogenic infarction.
o Chronic infarct: most often due to atherosclerosis  leads to fibrosis and stricture.
IV. ***Differential of bowel strictures:
1. Chronic ischemia from atherosclerosis  fibrosis
2. Crohn’s disease  hypertrophy and hyperplasia of MM
3. Tumor
4. Diverticulitis
G. COLONIC DIVERTICULOSIS (“TICKS”)
I. General
o Uncommon in pt <40y/o
o Caused by low fiber diet = much more common in western world
o ~90% in sigmoid colon
II. Characteristics
* These are acquired pseudodiverticulum!! True diverticulum (ex. meckels’s) is far more rare.
o Mucosa and submucosa herniate though the muscularis propria at a point of weakness (usually where a blood
vessel penetrates)
III. Complications and Associations
1. Complications
o Diverticulitis: inflammation of the diverticulum from impaction, bacterial overgrowth, etc…
o Perforation: leads to peritonitis, abscess formation and/or sepsis.
2. Associations
o 1. Polypoid prolapsing mucosal folds (PPMFs)- prolapse related polyps that develop around diverticula
o 2. Diverticular disease associated colitis- mimics IBD but has segmental distribution which is centered only
around diverticula.
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Lecturer: Ashlie L. Burkart
David Reilly
Lecture: 3
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Lecturer: Ashlie L. Burkart
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Lecture: 3
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