The Pathology
of
Intestines I
Developmental anomalies
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Atresia (bowel): complete failure of
development of the intestinal lumen (imperforate
anus)
Stenosis (bowel): narrowing of the intestinal
lumen
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Duplication (small intestine): well-formed
saccular-tubular cystic spaces (may or may not
communicate with the lumen).
Omphalocele (small intestine): a membranous
sac; herniation.
Malrotation (bowel): malposition of the large
intestinal components (caecum in the left upper
quadrant).
Meckel diverticulum: (small intestine)
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Common; in ileum;
Failure of involution of the omphalomesenteric (vitelline)
duct which connects the lumen of the developing gut to
the yolk sac ;
Persistent blind-ended tubular protrusion (5-6 cm long);
Contains all three layers of the normal bowel wall:
mucosa, submucosa, and muscularis propria;
Asymptomatic
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Pernicious anemia-like syndromes (bacteria B12 depletion);
Acute appendicitis-like syndrome (heterotopic rests of gastric
mucosa Peptic ulcerationbleeding).
Hirschsprung’s Disease (Congenital Megacolon)
Pathogenesis:
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The enteric neuronal plexus develops from 
neural crest cells  which must migrate into the bowel wall during
development mostly in a cephalad-to-caudad direction.
Congenital megacolon, or Hirschsprung’s disease, results when the
migration of neural crest cells arrests at some point before reaching the
anus.
Hence a segment remains that lacks both Meissner’s submucosal and
Auerbach’s myenteric plexuses.
Loss of enteric neuronal coordination leads to


(1) functional obstruction
(2) colonic dilatation proximal to the affected segment.
Occurs in approximately 1 out of 5000 to 8000 live births
M/F : 4/1
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Hirschsprung’s disease is characterized by the absence of
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ganglion cells,
ganglia,
in the muscle wall and submucosa of the affected segment.
The rectum is always affected, (most cases involve the rectum
and sigmoid only),
Proximal to the aganglionic segment, the colon undergoes
progressive dilatation and hypertrophy.
With time, the colon may become massively distended,
sometimes achieving a diameter of 15 to 20 cm (megacolon)
The colonic wall becomes markedly thinned and may rupture,
usually near the caecum.
Mucosal inflammation or shallow stercoral ulcers produced by
impacted feces may appear.
Enterocolitis.
Acquired megacolon

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(1) Chagas’ disease (in which the trypanosomes directly
invade the bowel wall to destroy the enteric plexuses);
(2) obstruction of the bowel as by a neoplasm or
inflammatory stricture;
(3) toxic megacolon complicating ulcerative colitis or
Crohn’s disease
(4) a functional psychosomatic disorder.
Vascular disorders

Ischemic Bowel
Disease
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Arterial thrombosis
Arterial embolism
Venous thrombosis
Nonocclusive ischemia
Miscellaneous: radiation injury,
volvulus, stricture, and internal or
external herniation.

Angiodysplasia
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Hemorrhoids
Ischemic Bowel Disease
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Restricted to the small or large intestine or
may affect both,
Acute occlusion of one of the three major
supply trunks of the intestines (celiac and
superior and inferior mesenteric arteries)
infarction.
Lesions within the end-arteries, which
penetrate the gut wall, produce small, focal
ischemic lesions.

The severity of injury ranges from
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(1) transmural infarction of the gut,
involving all visceral layers (acute occlusion
of a major artery);
(2) mural infarction of the mucosa and
submucosa;
(3) mucosal infarction (erosions), if the
lesion extends no deeper than the
muscularis mucosa.

Arterial embolism:
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cardiac vegetations,
angiographic procedures,
aortic thromboembolism.
Arterial thrombosis:
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severe atherosclerosis (a.mesenterica),
systemic vasculitis (polyarteritis nodosa),
dissecting aneurysm,
angiographic procedures,
aortic reconstructive surgery,
surgical accidents,
hypercoagulable states,
oral contraceptives.
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Venous thrombosis:
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hypercoagulable states,
oral contraceptives,
antithrombin III deficiency,
intraperitoneal sepsis,
the postoperative state,
invasive neoplasms (particularly hepatocellular
carcinoma),
cirrhosis,
abdominal trauma.
Nonocclusive ischemia:
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Miscellaneous:
-Radiation
-Volvulus
-Stricture
-herniation
cardiac failure,
shock,
dehydration,
vasoconstrictive drugs (digitalis, vasopressin, cocaine,
heroin).
Morphology
Transmural Infarction:
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Sudden and total occlusion of mesenteric arterial blood
 intestinal infarction.
Arterial or venous occlusionhemorrhagic infarct,
ischemic injury  mucosal necrosis  18-24 h 
fibrinous exudate over the serosa
Margins of the infarct:
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in arterial occlusions : distinct (demarcation)
in venous occlusions : less distinct
Microscopy: edema, interstitial hemorrhage, necrosis
(24 h)gangreneperforationperitonitis !!!
Mural & Mucosal Infarction:
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In any level of the gut from the stomach to anus
lesions may be multifocal-scattered or
continuous-widely distributed (depends on the
level of the arterial narrowing),
does not affect the entire thickness (may not be
visible from the serosal surface),
on opening the bowel, there is hemorrhagic,
edematous thickening of the mucosa.
Superficial ulcerations with
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edema,
hemorrhage,
fibrinous inflammation (psedomembrane due to
superinfection).
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Chronic Ischemia:
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Chronic vascular insufficiency  mucosal
inflammation and ulceration
Submucosal chronic inflammation and fibrosis 
stricture.
Segmental and patchy.
Angiodysplasia
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Tortuous dilatations of submucosal and mucosal
blood vessels
most often in the cecum or right colon
after the sixth decade of life
intestinal bleeding:
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chronic and intermittent (anemia)
acute and massive.
Hemorrhoids
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Variceal dilatations of the anal and perianal
venous plexuses
Persitently elevated venous pressure within the
hemorrhoidal plexus
Predispositions:
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chronic constipation,
pregnancy.
Thin-walled, dilated vessels
Complications: Bleeding, prolapsing.
Diarrheal diseases
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Diarrhea is an increase in stool:
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Mass
Frequency
Fludity
Disentery is a kind of diarrhea with:
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Low-volume
Pain
Hemorrhage
Diarrhea
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1. Secretory diarrhea
2. Osmotic diarrhea
3. Exudative diarrhea
4. Malabsorption
5. Deranged motility
1. Secretory diarrhea
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Intestinal fluid secretion (catarrh)
Serous
Causes:
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Infection (bacteria, virus)
Neoplastic (secretion of peptides and serotonin)
Excessice laxative use
2. Osmotic diarrhea
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Excessive osmotic forces
Causes:
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Lactulose therapy (hepatic encephalopathy,
constipation)
Gut lavage
Antacids (magnesium salts)
3. Exudative diarrhea
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Purulent/bloody stool
Causes:

Infections
escherichia,
 campylobacter,
 shigella,
 salmonella,
 Entamoeba histolytica,
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Idiopathic inflammatory bowel disease
4. Malabsorption
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Voluminous, bulky stool
Causes:
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Defective intraluminal digestion
Defective mucosal cell absorption
Reduced small intestinal surface area
Lymphatic obstruction
Infection (Giardia)
5. Deranged motility
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Decreased intestinal retention time
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Surgical reduction of gut length
Neural dysfunction (irritable bowel syndrome)
Hyperthyroidism
Decreased motility
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Surgery
Bacterial overgrowth in the small intestine
Infectious enterocolitis
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Intestinal diseases of microbial origin
Diarrhea and sometimes ulceroinflammatory
changes
Most common offenders
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rotavirus
Norwalk virus
Enterotoxigenic Escherichia coli

Offenders vary with the
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age,
nutrition,
immune status of the host,
environment (living conditions, public health
measures),
Special predispositions:
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hospitalization,
wartime dislocation,
foreign travel.
Viral Gastroenterocolitis

The small intestinal mucosa usually exhibits
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shortened villi
infiltration of the lamina propria by lymphocytes
vacuolization and loss of the microvillus brush
border in surface epithelial cells
crypts appear hypertrophied
viral particles within surface epithelial cells by
electron microscopy and in stool.
Bacterial Gastroenterocolitis

Numerous bacteria and several pathogenic mechanisms:

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Ingestion of preformed toxin, present in contaminated food
(major offenders are Staphylococcus aureus, Vibrios, and
Clostridium perfringens)
Infection by toxigenic organisms (which proliferate within the
gut lumen and elaborate an enterotoxin)
Infection by enteroinvasive organisms (which proliferate,
invade, and destroy mucosal epithelial cells)

Most bacterial infections exhibit a general
nonspecific pattern:
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damage of the surface epithelium
decreased epithelial cell maturation
an increased mitotic rate (“regenerative change”)
hyperemia and edema of the lamina propria
variable neutrophilic infiltration into the lamina
propria and epithelial layer.

Salmonella (multiple species, including S.
typhimurium and S. paratyphi):
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primarily ileum and colon
blunted villi,
vascular congestion,
Peyer’s patch involvement with swelling,
congestion,
ulceration (linear ulcers)
Typhoid fever : may result in chronic infection of
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biliary tree,
joints,
bones,
meninges.
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Shigella
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primarily distal colon
acute mucosal inflammation and erosion
purulent exudate
Campylobacter
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small intestine, appendix, colon
villus blunting
multiple superficial ulcers
mucosal inflammation
purulent exudate
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Yersinia enterocolitica and Y. pseudotuberculosis:
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V. cholerae:
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ileum, appendix, and colon
mucosal hemorrhage and ulceration
bowel wall thickening
Peyer’s patch and mesenteric lymph node hypertrophy with
necrotizing granulomas
systemic spread (with peritonitis, pharyngitis, pericarditis 
3-Ps)
essentially intact small intestinal mucosa,
with mucus-depleted crypts
C. perfringens:
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similar to V. cholerae but with some epithelial damage;
some strains produce a severe necrotizing enterocolitis with
perforation.
Necrotizing Enterocolitis
Neonates (premature or of low birth weight)
 acute, necrotizing inflammation.
 A combination of
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ischemic injury,
colonization by pathogenic organisms,
excess protein substrate in the intestinal lumen,
functional immaturity of the neonatal gut.
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The disease may present as a mild gastrointestinal
disturbance or as a fulminant illness with
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intestinal gangrene,
perforation,
sepsis,
shock.
Terminal ileum and ascending colon,
 although in severe cases, the entire small and large
bowel may be involved.
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In early phases, the mucosa exhibits
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As the disease progresses, the full thickness of
the bowel wall becomes
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edema,
hemorrhage,
necrosis
hemorrhagic,
inflamed,
gangrenous
frank intraluminal hemorrhage
mural gas formation
Reparative changes
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epithelial regeneration
granulation tissue formation
fibrosis.
Antibiotic-Associated Colitis
(Pseudomembranous Colitis)
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C. difficile (a normal gut commensal)
acute colitis
plaque-like adhesion of fibrinopurulent-necrotic
debris and mucus to damaged colonic mucosa
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following a course of broad-spectrum
antibiotic therapy
also may occur following any severe mucosal
injury,
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ischemic colitis,
volvulus,
necrotizing infections (staphylococci, shigella,
candida, necrotizing enterocolitis)
Malabsorption Syndromes
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Malabsorption is characterized by suboptimal
absorption of fats, fat-soluble and other
vitamins, proteins, carbohydrates, electrolytes
and minerals, and water.
The consequences of malabsorption affect
many organ systems.
Etiology
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Mal-digestion:
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Exocrine pancreatic disease
Lack of bile salts
Disaccharidase (lactase, etc.)
deficiency
Problems with the small
bowel mucosa:
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Sprue
Crohn's disease
Whipple's disease
Acute infections
Parasites (Giardia)
Allergic gastroenteritis
Amyloidosis
Lymphomas
Radiation sickness / B12 /
folate deficiency
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Super-fast transit time:
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Laxatives
Cholera
Vasoactive intestinal
polypeptide-producing tumors
Mechanical problems:
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Blocked lymphatics (cancer,
TB)
After re-routing surgery
(gastrectomy, bypass)
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Clinicopathology
Alimentary tract:
 Skin:
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Hematopoietic system:
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diarrhea
abdominal pain
weight loss
vitamin deficiencies
anemia (iron, pyridoxine,
folate, or vitamin B12
deficiency)
bleeding (vitamin K
deficiency)
Nervous system:
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peripheral neuropathy
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Musculoskeletal system:
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purpura and petechiae
edema
dermatitis
hyperkeratosis
osteoporosis
tetany
Endocrine system:
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amenorrhea
impotence
infertility
hyperparathyroidism
Celiac sprue
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Small intestine
idiosyncratic reaction to gliadin, a protein in the
gluten of wheat, rye, and barley
an antibody against the transglutaminase
activated cytotoxic killer-T cells invade the
epithelium
Microscopy:
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villi disappear
crypts deepen
Whipple's disease
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Small intestine & systemic
lipid pools in the mucosa
Tropheryma whippelii
(~actinomyces)
bacilli-laden macrophages in:
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gut mucosa
lymph nodes,
joints,
endocardium
brain.
IDIOPATHIC INFLAMMATORY
BOWEL DISEASES
Crohn’s Disease
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Idiopathic
Western developed
populations
limited to the terminal
ileum (terminal ileitis)
segmental lesions with
intervening unaffected
(“skip”) areas (regional
enteritis)

any level of the
alimentary tract with
systemic manifestations
Crohn’s disease: Morphology

Early disease:
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focal mucosal ulcers

Progressive disease:
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mucosal ulcers
coalescelong, serpentine
“linear ulcers”
tend to be oriented along
the axis of the bowel
mucosa acquires a
coarsely textured,
“cobblestone” appearance

narrow fissures
penetrating deeply
through the bowel wall
perforation or localized
abscesses
Hallmark: sharp
demarcation of
diseased bowel
segments from
adjacent uninvolved
bowel.
Crohn’s disease: Morphology

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Serosa: granular and dull gray
Mesentery: thickened,
edematous, and sometimes
fibrotic
Intestinal wall: rubbery and
thick (edema, inflammation,
fibrosis, hypertrophy of the
muscularis)
Lumen: narrowed (x-ray film
of small intestine shows
“string sign” )
Segmental disease: sharp
demarcation of diseased bowel
segments from adjacent
uninvolved bowel.
Crohn’s disease: Morphology

Microscopic Characteristics:
Transmural involvement of the bowel by
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Fissuring and formation of fistulas
Crypt destruction
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inflammatory process
mucosal damage
noncaseating granulomas(50%)
lymphoid aggregates
fibrosisstrictures
progressive atrophy
Paneth cell metaplasia
Ulcerative colitis
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An ulceroinflammatory
disease
limited to the colon
affecting only the
mucosa and submucosa
extends in a continuous
fashion proximally from
the rectum (in contrast
to Crohn’s disease)
granulomas are absent

Systemic disorder
(similar to Crohn’s disease)
 migratory polyarthritis,
 sacroiliitis,
 ankylosing spondylitis,
 uveitis,
 hepatic involvement
(pericholangitis and
primary sclerosing
cholangitis),
 skin lesions.


Involves the rectum
and extends
proximally in a
retrograde fashion to
involve the entire
colon (“pancolitis”) in
the more severe
cases.
It is a disease of
continuity

“skip” lesions such as
occur in CD are not
found
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In 10% of patients
with severe pancolitis,
the distal ileum may
develop mild mucosal
inflammation
(“backwash ileitis”).
The appendix may be
involved with both CD
and UC.
The mucosa exhibits
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slight reddening
granularity
friability
easy bleeding

Fully developed
severe, active
inflammation:
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
extensive and broadbased ulceration of the
mucosa in the distal
colon or throughout its
length
Isolated islands of
regenerating mucosa
bulge upward to create
“pseudopolyps.”
Often the undermined
edges of adjacent
ulcers interconnect to
create tunnels covered
by tenuous mucosal
bridges.

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The ulcers are frequently
aligned along the axis of
the colon (as with CD)
In contrast to Crohn’s
disease:

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rarely do the linear
serpentine ulcers
mural thickening does not
occur
Progressive mucosal
atrophy in chronic cases
Microscopy:
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
diffuse mononuclear
inflammatory infiltrate in the
lamina propria, admixed with
neutrophils
occasional eosinophils and
mast cells.
Diffuse mononuclear cell infitration
Pseudopolyps (carpet-like mucosa)
pseudopolyp
ulcer
Crypt abscess
Crypt abscess
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Long-term complication
of UC : cancer.
Particular attention to:

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epithelial changes
signifying dysplasia and
the progression to frank
carcinoma
Underlying
inflammatory disease
may mask the
symptoms and signs of
carcinoma

The risk of cancer
is highest in patients
with pancolitis of 10
or more years’
duration, in whom it
exceeds by 20-fold
to 30-fold that in a
control population.
Malabsorption Syndromes
Celiac sprue
Gluten (gladin)
Whipple's disease Tropherhyma
whipplii
Small intestine
villi disappear
crypts deepen
Small intestine
bacilli-laden macrophages
(lymph nodes, joints,
endocardium and/or
brain)
Bacterial
Overgrowth
Syndrome
Aerobic and
anaerobic
organisms
Proximal small
Disaccharidase
deficiency
Less intestinal
lactase
Small intestine
Abetalipoproteinemia
Inability to
All
enterocytes loaded with
dietary fat
Terminal ileum
noncaseating granulomas
Crohn’s Disease
Ulcerative Colitis
bowel
immunedeficiencies
synthesize
Idiopathic
luminal stasis,
hypochlorhydria,
osmotic diarrhea
and ulcers with perforation
Idiopathic
Colon
Severe active inflammation,
ulcers & pseudopolyps

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


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Location
Bowel
Terminal ileum
Colon
Anal troubles
Oral lesions
Skip lesions
Layers
Ulcers
Pseudopolyps
Fibrosis
Fistulas
Granulomas
Bleeding
Carcinoma risk
Crohn's disease
Variable
Small
Favorite site
Right more than left
Common
Maybe
+
All three
Linear fissures
+++
+++
+
+
Subtle
+
Ulcerative colitis
Rectum and upwards
Large
"Backwash"
Left more than right
No; continuous
Mucosa only
Broad / irregular
++
Heavy-duty
+++
Colonic Diverticulosis


A diverticulum is a blind
pouch leading off the
alimentary tract, lined by
mucosa that
communicates with the
lumen of the gut
Acquired diverticula may
occur in the esophagus,
stomach, and duodenum;
duodenal diverticula occur
in more than 1% of adults


Congenital
diverticula (Meckel’s
diverticulum) have
all three layers of
the bowel wall;
all other diverticula
are acquired and
either lack or have
an attenuated
muscularis propria.


Histology:
 a thin wall composed
of a flattened or
atrophic mucosa,
 compressed
submucosa,
 attenuated or totally
 descending colon or
absent muscularis
entire colon, however,
propria
may be affected
 hypertrophy of the
Pathogenesis
circular layer of the
 (1) focal weakness in the
muscularis propria in
colonic wall
the affected bowel
 (2) increased intraluminal
segment is usually
pressure.
seen.
Most colonic diverticula
are small flask-like or
spherical outpouchings,
usually 0.5 to 1 cm in
diameter and located in
the sigmoid colon

Complications




Obstruction
Perforation
Marked fibrotic
thickening due to the
inflammation
Narrowing (resembles
colonic cancer)

Diverticular infection



pericolic abscesses
sinus tracts
pelvic or generalized
peritonitis.
Bowel Obstruction

Mechanical obstruction

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Adhesions (post-op, Crohn's)
Hernias
Volvulus
Intussusception
Tumors
Inflammatory strictures
Obstructive material (gallstone,
fecalith, foreign body)
Congenital



Atresia of the anus / imperforate
anus
Congenital atresia / strictures
Meconium ileus (cystic fibrosis)
Pseudo-obstruction



Paralytic ileus
Vascular bowel infarction
Myopathies & neuropathies
(Hirschsprung’s disease)
Bowel Obstruction : Hernias


A weakness or defect in the
wall of the peritoneal cavity
may permit protrusion of a
pouch-like, serosa-lined sac
of peritoneum, called a
hernial sac.
The usual sites:



anteriorly at the inguinal and
femoral canals,
umbilicus,
surgical scars.

Intruders :




small bowel loops,
omentum,
large bowel.
Pathology:




impair venous drainage
of the trapped viscus
stasis and edema
compromise of arterial
supply and venous
drainage (strangulation)
infarction of the trapped
segment.
Bowel Obstruction : Adhesions

Peritonitis:




surgical procedures,
infection,
endometriosis.
As the peritonitis heals:


adhesions (between bowel
segments or the abdominal
wall and operative site)
fibrous bridges  closed
loops  trapped intestine
(internal herniation).

The sequence of events
following herniation:


obstruction
strangulation.
Bowel Obstruction : Intussusception

Intussusception occurs
when one segment of
the small intestine,
constricted by a wave of
peristalsis, suddenly
becomes telescoped
into the immediately
distal segment of
bowel.

Once trapped, the
invaginated segment is
propelled by peristalsis
farther into the distal
segment, pulling its
mesentery along behind
it.

Clinical:


intraluminal mass or
tumor as the point of
traction.
Complications:


intestinal obstruction
infarction.
Bowel Obstruction : Volvulus


Complete twisting of a
loop of bowel about its
mesenteric base of
attachment
produces intestinal
obstruction and
infarction.





Sigmoid,
cecum,
small bowel (all or
portions),
stomach,
transverse colon (rarely).