SMALL AND LARGE INTESTINES

1
2
3
4
 SMALL AND LARGE INTESTINES

• INTESTINAL OBSTRUCTION
• VASCULAR DISORDERS OF BOWEL
• MALABSORPTION AND DIARRHEA
• INFLAMMATORY INTESTINAL DISEASE
• COLONIC POLYPS AND NEOPLASTIC DISEASE

5
 SMALL INTESTINE AND COLON
• Intestinal Obstruction
– Hernias
– Adhesions
– Volvulus
– Intussusception
• Vascular Disorders of Bowel
– Ischemic Bowel Disease
– Angiodysplasia
• Malabsorption and Diarrhea
– Cystic Fibrosis
– Celiac Disease
– Environmental Enteric Dysfunction
– Autoimmune Enteropathy
– Lactase (Disaccharidase) Deficiency
– Microvillus Inclusion Disease
– Abetalipoproteinemia
• Infectious Enterocolitis
– Cholera
– Campylobacter Enterocolitis
– Shigellosis
– Salmonella
– Typhoid Fever
– Yersinia
– Escherichia coli
– Pseudomembranous Colitis
– Whipple Disease
– Viral Gastroenteritis
– Parasitic Enterocolitis
• Irritable Bowel Syndrome
• Inflammatory Bowel Disease (IBD)
– Crohn Disease
– Ulcerative Colitis
– Indeterminate Colitis
– Colitis-Associated Neoplasia
• Other Causes of Chronic Colitis
– Diversion Colitis
– Microscopic Colitis
• Graft-Versus-Host Disease
• Sigmoid Diverticular Disease
• Polyps
– Hyperplastic Polyps
– Inflammatory Polyps
– Hamartomatous Polyps
• Juvenile Polyps
• Peutz-Jeghers Syndrome
– Neoplastic Polyps
– Familial Adenomatous Polyposis
• Hereditary Non-Polyposis Colorectal Cancer
(HNPCC)
• Adenocarcinoma
• Anal Canal disorders
– Tumors of the Anal Canal
– Hemorrhoids
• Appendix
– Acute Appendicitis
6
– Tumors of the Appendix
 INTESTINAL OBSTRUCTION

• Hernias
• Intestinal adhesions Account for 80% of mechanical
• Intussusception obstructions
• Volvulus
• Stasis - edema - permanent entrapment (incarceration) - arterial and venous
compromise (strangulation) - infarction
• Tumors and infarction account for most of the remainder.
• The clinical manifestations; abdominal pain and distention, vomiting, and
constipation.
• Surgical intervention usually is required

7
Intestinal obstruction: Dusky areas of serosa and associated hemorrhage indicate
ischemic damage. 8
 SMALL AND LARGE INTESTINES

• INTESTINAL OBSTRUCTION
• VASCULAR DISORDERS OF BOWEL
• MALABSORPTION AND DIARRHEA
• INFLAMMATORY INTESTINAL DISEASE
• COLONIC POLYPS AND NEOPLASTIC DISEASE

9
 Ischemic Bowel Disease
• Supplied by the celiac, superior mesenteric, and inferior mesenteric arteries.
• Mucosal infarction: no deeper than the muscularis mucosa
• Mural infarction: mucosa and submucosa
• Transmural infarction: all three layers of the wall
• Intestinal vascular anatomy and distribution of ischemic damage:
– Intestinal segments at the end arterial supplies are susceptible to ischemia
(watershed zones)
– The arrangement of capillaries makes the surface epithelium vulnerable to
ischemic injury
• Mucosal or mural infarctions are secondary to acute or chronic hypoperfusion
• Transmural infarction is caused by acute vascular obstruction
– Acute obstruction due to thrombosis or embolism; severe atherosclerosis (the
most important risk factor)
– Systemic vasculitides
– Obstructive emboli from aortic atheromas or cardiac mural thrombi.
– Mesenteric venous thrombosis; inherited or acquired hypercoagulable states,
invasive neoplasms, cirrhosis, trauma, abdominal masses that compress the portal
drainage.
– Intestinal hypoperfusion in the setting of cardiac failure, shock, dehydration, or
use of vasoconstrictive drugs.
10
 Ischemic Bowel Disease
MORPHOLOGY
• Segmental and patchy in distribution
• The mucosa is hemorrhagic and often ulcerated
• Wall is thickened by edema
• With severe disease, extensive mucosal and
submucosal hemorrhage and necrosis
• Blood-tinged mucus or blood accumulates within the
lumen.
• Coagulative necrosis of the muscularis propria
• In mesenteric venous thrombosis, arterial blood
continues to flow: bleeding
• Microscopic examination; atrophy or sloughing of
surface epithelium
– Crypts may be hyperproliferative.
– Inflammatory infiltrates: neutrophils
– Chronic ischemia: fibrous scarring of l. propria 11
 Other vascular Disorders
• Radiation enterocolitis ; epithelial and vascular injury
• The presence of bizarre “radiation fibroblasts”
• Acute radiation enteritis: anorexia, abdominal
cramps, and a malabsorptive diarrhea.
• Chronic radiation enteritis or colitis often is more
indolent and may present as an inflammatory colitis.
• Necrotizing enterocolitis: an acute disorder , result in
transmural necrosis.
– most common acquired gastrointestinal emergency
of neonates: premature or low birth weight
• Angiodysplasia : malformed submucosal and mucosal
blood vessels.
– the cecum or right colon, after the sixth decade of
life
– Major episodes of lower intestinal bleeding; chronic
and intermittent or acute and massive.
12
 SMALL AND LARGE INTESTINES
• INTESTINAL OBSTRUCTION
• VASCULAR DISORDERS OF BOWEL
• DIARRHEAL DISEASE
– Malabsorptive Diarrhea
– Infectious Enterocolitis
• INFLAMMATORY INTESTINAL DISEASE
• COLONIC POLYPS AND NEOPLASTIC DISEASE

13
 Diarrhea
• Diarrhea : an increase in stool mass, frequency, or fluidity, typically to
volumes greater than 200 mL per day.
• Painful, bloody, small-volume diarrhea is known as dysentery.
• Diarrhea can be classified into four major categories:
– Secretory diarrhea is characterized by isotonic stool and persists
during fasting.
– Osmotic diarrhea; due to osmotic forces of unabsorbed luminal
solutes, such as lactase deficiency.
• The diarrheal fluid is more concentrated than plasma, and the
condition abates with fasting.
– Malabsorptive diarrhea caused by inadequate nutrient absorption is
associated with steatorrhea and is relieved by fasting.
– Exudative diarrhea is due to inflammatory disease and
characterized by purulent, bloody stools that continue during
fasting.

14
 Malabsorptive Diarrhea
• Malabsorption; chronic diarrhea
– Defective absorption of fats, fat- and water-soluble vitamins,
proteins, carbohydrates, electrolytes and minerals, and water.
• A hallmark of malabsorption is steatorrhea
– Excessive fecal fat and bulky, frothy, greasy, yellow or
clay-colored stools.
• The chronic malabsorptive disorders;
– Pancreatic insufficiency
– Celiac disease
– Crohn disease.
– Intestinal graft-versus-host disease
– Environmental enteropathy (previously known as tropical sprue)

15
 Malabsorptive Diarrhea
• Disturbance in at least one of the four phases of nutrient absorption:
• (1) intraluminal digestion: proteins, carbohydrates, and fats are broken down into
forms suitable for absorption
• (2) terminal digestion: the hydrolysis of carbohydrates and peptides
– by disaccharidases and peptidases in the brush border of the small intestinal
mucosa
• (3) transepithelial transport; nutrients, fluid, and electrolytes are transported across
and processed within the small intestinal epithelium
• (4) lymphatic transport of absorbed lipids
• Symptoms and signs : diarrhea, flatus, abdominal pain, and weight loss.
• Inadequate absorption of vitamins and minerals ;
– anemia and mucositis due to pyridoxine, folate, or vitamin B12 deficiency
– bleeding due to vitamin K deficiency
– osteopenia and tetany due to calcium, magnesium, or vitamin D deficiency
– neuropathy due to vitamin A or B12 deficiency
– A variety of endocrine and skin disturbances also may occur. 16
17
 Cystic Fibrosis
• The absence of the epithelial cystic fibrosis transmembrane conductance
regulator (CFTR)
• Defects in intestinal and pancreatic ductal chloride ion secretion
– Interference with bicarbonate, sodium, and water secretion, ultimately
resulting in defective luminal hydration.
– Failure of hydration; meconium ileus, which is present in up to 10% of
newborns with cystic fibrosis.
– Obstruction, chronic autodigestion of the pancreas, and eventual
exocrine pancreatic insufficiency in more than 80% of patients.

• Failure of the intraluminal phase of nutrient absorption: treated with oral

enzyme supplementation.

18
 Celiac Disease
• Celiac disease; celiac sprue or
gluten-sensitive enteropathy

• An immune-mediated enteropathy

• Triggered by the ingestion of

gluten-containing cereals (wheat, rye, or
barley)

• Genetically predisposed persons.

• The primary treatment for celiac disease is a

gluten free diet.

• Adhering to such a diet, result in

symptomatic improvement for most
patients.

19
 Celiac Disease - PATHOGENESIS
• An intestinal immune reaction to gluten
• Gluten is digested by luminal and brush border enzymes
• A 33–amino acid gliadin peptide reveal
• Antigen-presenting cells present to CD4+ T cells.
– T cells produce cytokines: the tissue damage
– B cell response : anti-tissue transglutaminase, anti-deamidated
gliadin, anti-endomysial antibodies
– İntraepithelial CD8+ cells: tissue damage
• Host factors determine whether disease develops
– HLA proteins : class II HLA-DQ2 or HLA-DQ8 alleles.

20
Left panel, The morphologic alterations that may be present in celiac disease, including villous atrophy,
increased numbers of intraepithelial lymphocytes (IELs), and epithelial proliferation with crypt elongation.
Right panel, A model for the pathogenesis of celiac disease.
21
 Celiac Disease - MORPHOLOGY
• Biopsy specimens from the second
portion of the duodenum or
proximal jejunum
• Intraepithelial CD8+ T lymphocytes
(intraepithelial lymphocytosis),
crypt hyperplasia, and villous
atrophy (Marsh-Oberhuber
classification)
• Increased numbers of plasma cells,
mast cells, and eosinophils,
especially within the upper part of
the lamina propria.
• The combination of histologic and
serologic findings is most specific
for diagnosis of celiac disease.
22
 Pathologica, v.112(3); 2020 Sep

(A-B): normal duodenal mucosa; villous/crypt ratio over 3:1; number of T lymphocytes < 25 x 100 epithelial
cells.
(C-D): Type 1 - Grade A lesion; normal villi but with pathological increase of T lymhocytes > 25 x 100
epithelail cells.
(E-F): mild to moderate villous atrophy Type 3A-3B - Grade B1 with pathological increase of T
lymphocytes.
(G-H): severe villous atrophy Type 3C - Grade B2 with pathological increase of T lymphocytes. 23
 Celiac Disease - Clinical Features
• Adult: Between the ages of 30 and 60
• May be silent (latent) or symptomatic
• Anemia (due to iron deficiency and, less commonly, B12 and folate deficiency),
diarrhea, bloating, and fatigue.
• Pediatric celiac disease:
• Classic symptoms: between the ages of 6 and 24 months
• Abdominal distention, anorexia, diarrhea, failure to thrive, weight loss, or muscle
wasting.
• Nonclassic symptoms: older ages with complaints of abdominal pain, nausea,
vomiting, bloating, or constipation.
• Dermatitis herpetiformis (a characteristic pruritic, blistering skin lesion): 10% of
patients
• Serologic tests: IgA antibodies to tissue transglutaminase , IgA or IgG antibodies to
deamidated gliadin, antiendomysial antibodies
• Enteropathy-associated T cell lymphoma, an aggressive tumor of intraepithelial T
lymphocytes and small intestinal adenocarcinoma is more frequent.
24
 Environmental Enteric Dysfunction
(Environmental (Tropical) Enteropathy)
• Environmental enteropathy (tropical sprue); a syndrome of stunted
growth and impaired intestinal function
• Common in developing countries
• Affect over 150 million children worldwide
• Neither supplementary feeding nor vitamin and mineral
supplementation are able to fully reverse the syndrome.
• Repeated bouts of diarrhea suffered within the first 2 or 3 years of life
• No single infectious agent has been linked
• Histologic features are similar to those of severe celiac disease
• Recurrent diarrhea establishes a cycle of mucosal injury, malnutrition,
infection, and inflammation.

25
 Autoimmune Enteropathy
• An X-linked disorder characterized by
severe persistent diarrhea and
autoimmune disease that occurs most
often in young children.
• IPEX; immune dysregulation,
polyendocrinopathy, enteropathy, and
X-linkage
– Germline loss of function
mutations in the FOXP3 gene on
the X chromosome.
– Defective development and
function of CD4+ cells
• Autoantibodies to enterocytes and
goblet cells
• Intraepithelial lymphocytes may be
increased, also neutrophils.

26
 Lactase (disaccharidase) Deficiency
• Congenital lactase deficiency;
– Autosomal recessive disorder caused by a mutation in the gene encoding
lactase.
• Manifests as explosive diarrhea with watery, frothy stools and abdominal
distention after milk ingestion.
• Symptoms abate when exposure to milk and milk products is terminated
• Acquired lactase deficiency;
• Downregulation of lactase gene expression
• Common among Native Americans, African Americans, and Chinese
populations.
• Onset of acquired lactase deficiency is sometimes associated with enteric viral
or bacterial infections.

27
 Microvillus Inclusion Disease
• Sometimes referred to as Davidson disease
• An autosomal recessive disorder of vesicular transport that leads to
deficient brush-border assembly
• Mutations in the MYO5B gene; encodes a motor protein that is required
– For delivery and retrieval of plasma membrane components
– For normal nutrient, ion, and water transport.
• The disease occurs most commonly in European, Middle Eastern, and
Navajo Native American populations.
• Severe, intractable diarrhea develops before 3 months of age (often in the
first few days of life)
– A result of defective terminal digestion and transepithelial transport
functions.
• The accumulation of abnormal apical vesicles containing microvilli and
various membrane components.
– Identified by electron microscopy
– IHC; immunostaining for the brush border protein villin and CD10
• Treatments: Total parenteral nutrition and small bowel transplantation
28
Microvillus Inclusion Disease

29
 Abetalipoproteinemia
• An autosomal recessive disease
• An inability to assemble triglyceride-rich
lipoproteins.
• A transepithelial transport defect: mutation
in the microsomal triglyceride transfer
protein
– Monoglycerides and triglycerides
accumulate within the epithelial cells.
• Lipid vacuoles in small intestinal epithelial
cells
– special stains, such as oil red O
– particularly after a fatty meal.
• Failure to thrive, diarrhea, and steatorrhea.
• Deficiencies of fat-soluble vitamins
• Lipid defects in plasma membranes often
produce acanthocytic red cells (spur cells) in
peripheral blood smears.

30
31
 Infectious Enterocolitis
• Responsible for more than 12,000 deaths per day among children in
developing countries
• Half of all deaths before age 5 worldwide
• Bacterial infections, such as enterotoxigenic Escherichia coli, frequently
are responsible, but the most common pathogens vary with age,
nutrition, and host immune status, as well as environmental influences
• Epidemics of cholera are common in areas with poor sanitation
• Pediatric infectious diarrhea, which may result in severe dehydration
and metabolic acidosis, commonly is caused by enteric viruses.

32
 INFECTIOUS ENTEROCOLITIS
• Bacterial infections
– Cholera
– Campylobacter Enterocolitis
– Shigellosis
– Salmonella
– Typhoid Fever
– Yersinia
– Escherichia coli
– Pseudomembranous Colitis
– Whipple Disease
• Viral Gastroenteritis
– Norovirus
– Rotavirus
– Adenovirus
• Parasitic Enterocolitis
– Ascaris lumbricoides
– Strongyloides
– Necator duodenale and
Ancylostoma duodenale
– Trichuris trichiura
– Enterobius vermicularis and
Enterobius gregorii
– Schistosomiasis
– Intestinal Cestodes
– Entamoeba histolytica
– Giardia lamblia
– Cryptosporidium
33
34
35
 Whipple Disease
• Described an individual with malabsorption, lymphadenopathy, and arthritis of
undefined origin.
• The presence of foamy macrophages and large numbers of argyrophilic rods in
the lymph nodes, suggesting that the disease was caused by a microbe.
• The gram-positive actinomycete, named Tropheryma whippelii; responsible for
Whipple disease.
• Clinical symptoms due to organism-laden macrophages accumulating within the
small intestinal lamina propria and mesenteric lymph nodes, causing lymphatic
obstruction.
– The malabsorptive diarrhea due to impaired lymphatic transport.
• The morphologic hallmark of Whipple disease; a dense accumulation of
distended, foamy macrophages in the small intestinal lamina propria
– The macrophages contain periodic acid–Schiff (PAS)-positive,
diastase-resistant granules
– Lysosomes stuffed with partially digested bacteria
– Intact rod-shaped bacilli, by EM
36
Whipple disease
A, HE staining;
effacement of normal
lamina propria by a sheet
of swollen macrophages.
B, PAS stain;
macrophage lysosomes
full of bacilli
C,EM; bacilli within the
cell (top arrow); also
seen at higher
magnification (inset).

37
Mycobacterial infection;
D, The morphology of mycobacterial infection can be similar to
Whipple disease
E, Mycobacteria are positive with stains for acid-fast bacteria.
38
 INFECTIOUS ENTEROCOLITIS
• Bacterial infections
– Cholera
– Campylobacter Enterocolitis
– Shigellosis
– Salmonella
– Typhoid Fever
– Yersinia
– Escherichia coli
– Pseudomembranous Colitis
– Whipple Disease
• Viral Gastroenteritis
– Norovirus
– Rotavirus
– Adenovirus
• Parasitic Enterocolitis
– Ascaris lumbricoides
– Strongyloides
– Necator duodenale and
Ancylostoma duodenale
– Trichuris trichiura
– Enterobius vermicularis and
Enterobius gregorii
– Schistosomiasis
– Intestinal Cestodes
– Entamoeba histolytica
– Giardia lamblia
– Cryptosporidium
39
 INFECTIOUS ENTEROCOLITIS
Viral Gastroenteritis
• Norovirus; Norwalk-like virus, with a single-stranded RNA genome
– Approximately half of all gastroenteritis outbreaks worldwide
– Fecal-oral transmission
– Vomiting, cramping abdominal pain, watery diarrhea, and nonspecific
symptoms including headache, chills, and myalgias
– The malnutrition and dehydration
– Resistance to norovirus due to FUT2 mutations (%20)
• Rotavirus; double-stranded RNA genome
– Significant cause of diarrheal deaths worldwide
– Children between 6 and 24 months of age are most vulnerable
– Vaccines are widely used
– Infects and destroys mature enterocytes in the small intestine, the loss
of absorptive function
• Adenovirus
– A common cause of pediatric diarrhea, also affects
immunocompromised patients
– Epithelial degeneration, villous atrophy, crypt hyperplasia.
40
 INFECTIOUS ENTEROCOLITIS
Parasitic Enterocolitis
• Ascaris lumbricoides; an eosinophil-rich inflammatory reaction, physical obstruction
of the intestine or biliary tree, hepatic abscesses and pneumonitis.
• Strongyloides; penetrate unbroken skin, migrate through the lungs, reside in the
intestine, cause autoinfection, can persist for life, incite a strong tissue reaction and
peripheral eosinophilia.
• Necator duodenale and Ancylostoma duodenale: larval penetration through the
skin, development in the lungs, swallowed to attach to the duodenal mucosa, suck
blood, and reproduce. Causes superficial erosions, focal hemorrhage, inflammatory
infiltrates, and, in chronic infection, iron deficiency anemia.
• Trichuris trichiura; may cause bloody diarrhea and rectal prolapse.
• Enterobius vermicularis and Enterobius gregorii; irritation and rectal and perineal
pruritus
• Schistosomiasis; granulomatous infl., bleeding, obstruction
• Intestinal Cestodes (tapeworms); abdominal pain, diarrhea, nausea, B12 def
• Entamoeba histolytica; Dysentery, a flask-shaped ulcer, similar to macrophages
• Giardia lamblia; decreased expression of brush-border enzymes, microvillous
damage, and apoptosis of small intestinal epithelial cells, diarrhea, malabsorption,
and weight loss
• Cryptosporidium; causes changes in the enterocyte cytoskeleton, Sodium
malabsorption, chloride secretion, watery diarrhea. Villous atrophy, crypt
hyperplasia 41
Viral enteritis with increased
numbers of intraepithelial
lymphocytes
Diffuse eosinophilic infiltrates in
parasitic infection
42
Schistosomiasis eggs trapped Entamoeba histolytica ingesting red
within the lamina propria. blood cells

43
Giardia lamblia Cryptosporidium enveloped by a
thin layer of host cell cytoplasm

44
 SMALL AND LARGE INTESTINES
• INTESTINAL OBSTRUCTION
• VASCULAR DISORDERS OF BOWEL
• DIARRHEAL DISEASE
• INFLAMMATORY INTESTINAL DISEASE
– Sigmoid Diverticulitis
– Inflammatory Bowel Disease
• COLONIC POLYPS AND NEOPLASTIC DISEASE

45
 Sigmoid Diverticulitis
• Acquired pseudodiverticular
outpouchings of the colonic mucosa and
submucosa.
• Rare in persons younger than 30 years
of age, 50% of Western adult
populations older than age 60.
• Diverticula generally are multiple, and
the condition is referred to as
diverticulosis.
• Much less common in Japan and
nonindustrialized countries, because of
dietary differences.

46
 Sigmoid Diverticulitis - PATHOGENESIS
• Develop under conditions of
elevated intraluminal pressure in
the sigmoid colon.
• Nerves, arterial vasa recta, and
their connective tissue sheaths
penetrate the inner circular
muscle coat to create
discontinuities in the muscle
wall.
• High luminal pressures may be
generated by exaggerated
peristaltic contractions

47
 Sigmoid Diverticulitis - MORPHOLOGY
• Small, flask-like outpouchings, usually
0.5 to 1 cm in diameter
• In a regular distribution in between the
taenia coli
• Most common in the sigmoid colon
• Compressible, easily emptied of fecal
contents, often surrounded by the
fat-containing epiploic appendices
– They may be missed on casual
inspection.
• Have a thin wall composed of a flattened
or atrophic mucosa, compressed
submucosa Sigmoid diverticular disease.
– Can lead to perforation. A, Stool-filled diverticula are regularly
• Recurrent diverticulitis: segmental colitis, arranged.

fibrotic thickening in and around the B, Cross-section showing the outpouching of

colonic wall, or stricture formation.
• Perforation: pericolonic abscesses,
development of sinus tracts, peritonitis.
mucosa beneath the muscularis propria.
C, Low-power photomicrograph of a sigmoid
diverticulum showing protrusion of the mucosa
and submucosa through the muscularis 48
propria.
 Inflammatory Bowel Disease
• Inflammatory bowel disease (IBD) is a chronic condition resulting
from inappropriate mucosal immune activation.
• Two major entities;
– Crohn disease
– Ulcerative colitis
• The distinction is based on the distribution of affected sites and the
morphologic expression of disease at those sites
• Ulcerative colitis is limited to the colon and rectum and extends only
into the mucosa and submucosa.
• Crohn disease, which also has been referred to as regional enteritis
(because of frequent ileal involvement), may involve any area of the
gastrointestinal tract and frequently is transmural.

49
50
51
 IBD - Epidemiology
• More common in females
• Frequently present during adolescence or in young adults
• The geographic distribution highly variable: most prevalent in North America,
northern Europe, and Australia.
• The hygiene hypothesis: related to improved food storage conditions and
decreased food contamination.
– A reduced frequency of enteric infections
– Normally innocuous microbes later in life triggers inappropriate immune
responses

52
 IBD - PATHOGENESIS

• IBD results from a

combination of
abnormalities in immune
regulation, host-microbe
interactions, and
epithelial barrier
functions in genetically
susceptible individuals
• Genetic predisposition
(Polymorphisms of
NOD2) + environmental
factors

53
 IBD - PATHOGENESIS
• Genetics; NOD2 (nucleotide oligomerization binding domain 2) as a
susceptibility gene in Crohn disease.
– Other genes: ATG16L1 (autophagy-related 16– like-1), IRGM
(immunity-related GTPase M)
• Mucosal immune responses.
– Polarization of helper T cells to the TH1 type
– TH17 T cells also contribute to disease pathogenesis
– Certain polymorphisms of the IL-23 receptor confer protection from
Crohn disease and ulcerative colitis
• Autophagy and cellular stress responses: ATG16L1 and IRGM genes
mutations limiting autophagosome formation (a means of clearing sources
ROS and micobes)
• Epithelial defects: defects in intestinal epithelial tight junction barrier function
– Activate innate and adaptive mucosal immunity and sensitize subjects to
disease.
• Microbiota. The quantity of microbial organisms in the gastrointestinal lumen
– Transepithelial flux of luminal bacterial components activates innate and
adaptive immune responses.

54
 Crohn Disease - MORPHOLOGY I
• Known as regional enteritis
• May occur in any area of the
gastrointestinal tract.
• Presentation: terminal ileum, ileocecal
valve, and cecum.
• Limited to the small intestine: 40% of
cases
• Small intestine and the colon: 30% of
patients
• the remainder: colonic involvement
only
• Multiple, separate, sharply delineated
areas of disease
• Skip lesions: characteristic of Crohn
disease
• Strictures are common

55
 Crohn Disease - MORPHOLOGY II
• The earliest lesion: aphthous ulcer
• May progress, and multiple lesions often coalesce
• Edema and loss of normal mucosal folds
• Sparing of interspersed mucosa: cobblestone appearance
• Fissures frequently develop
• The intestinal wall is thickened: transmural edema, inflammation,
submucosal fibrosis, and hypertrophy of the muscularis propria
• In cases with extensive transmural disease, mesenteric fat frequently
extends around the serosal surface (creeping fat)
• Crypt abscesses, distortion and disorganization of mucosal glands
• Epithelial metaplasia; pseudopyloric metaplasia, Paneth cell metaplasia
• Noncaseating granulomas; a hallmark, in approximately 35% of cases
– Granulomas may also be present in draining mesenteric lymph nodes
– Cutaneous granulomas form nodules that are referred to (misleadingly)
as metastatic Crohn disease. 56
Small intestinal Linear mucosal ulcers and Creeping fat
stricture. thickened intestinal wall.

57
Microscopic pathology of
Crohn disease.
A, Haphazard crypt
organization results from
repeated injury and
regeneration.
B, Noncaseating granuloma.
C, Transmural Crohn disease
with submucosal and serosal
granulomas (arrows).

crypt abscess
58
59
 Ulcerative colitis
• Ulcerative colitis is closely related to Crohn disease.
• However, ulcerative colitis is limited to the colon and rectum.
• Some extraintestinal manifestations of ulcerative colitis overlap with
those of Crohn disease, including
– migratory polyarthritis,
– sacroiliitis,
– ankylosing spondylitis,
– uveitis,
– skin lesions,
– pericholangitis, and

– primary sclerosing cholangitis.

60
 Ulcerative colitis - MORPHOLOGY I
• Always involves the rectum, extends proximally in a continuous fashion to
involve part or all of the colon, skip lesions are not seen
• May cause pancolitis
• Disease limited to the rectum or rectosigmoid; ulcerative proctitis or
ulcerative proctosigmoiditis.
• The small intestine; usually normal, mild mucosal inflammation of the distal
ileum, backwash ileitis in severe cases of pancolitis.
• On gross evaluation, involved colonic mucosa may be slightly red and
granular-appearing or exhibit extensive broad-based ulcers.
• The transition between diseased and uninvolved colon can be abrupt
• Pseudopolyps; Small elevations of regenerating mucosa bulging into the
lumen
– The tips of these polyps may fuse to create mucosal bridges
– Chronic disease may lead to mucosal atrophy and a flat, smooth mucosal
surface lacking normal folds.
61
 Ulcerative colitis - MORPHOLOGY II
• Mural thickening is absent, the serosal surface is normal, and strictures do
not occur.
• Inflammation and inflammatory mediators can damage the muscularis
propria
• Disturbed neuromuscular function; colonic dilatation and toxic megacolon
– A significant risk of perforation.
• Histologic features of mucosal disease; similar to colonic Crohn disease
– Inflammatory infiltrates, crypt abscesses, crypt distortion, and epithelial
metaplasia.
– Skip lesions are absent and inflammation generally is limited to the
mucosa and superficial submucosa
• In severe cases, mucosal damage may be accompanied by ulcers that extend
more deeply into the submucosa, but the muscularis propria is rarely
involved.
• Submucosal fibrosis, mucosal atrophy, and distorted mucosal architecture
remain as residua of healed disease
– The histologic pattern also may revert to near normal after prolonged
remission.
• No granulomas 62
Pathology of ulcerative colitis.
A, Total colectomy with pancolitis showing active disease, with red, granular mucosa in the
cecum (left) and smooth, atrophic mucosa distally (right).
B, Sharp demarcation between active ulcerative colitis (bottom) and normal (top).
C, This full-thickness histologic section shows that disease is limited to the mucosa.

63
64
 Crypt abscess

Pseudopyloric metaplasia 65
66
 Indeterminate Colitis
• Histopathologic and clinical overlap between ulcerative colitis
and Crohn disease is common
– Not possible to make a distinction in up to 10% of patients
with IBD.
– The small bowel is not involved, and the continuous pattern
of colonic disease (indicate ulcerative colitis)
– Patchy disease, fissures, a family history of Crohn disease,
perianal lesions, onset after initiation of cigarette smoking
• Extensive overlap in medical management of ulcerative colitis
and Crohn disease

67
 Colitis-Associated Neoplasia
• One of the most feared long-term complications of ulcerative colitis and
colonic Crohn disease is the development of neoplasia.
• Begins as dysplasia
• The risk of dysplasia is related to several factors:
– Duration of the disease; Risk increases sharply 8 to 10 years after disease
initiation.
– Extent of the disease; Patients with pancolitis are at greater risk than
those with only left-sided disease.
– Nature of the inflammatory response; Greater frequency and severity of
active inflammation (characterized by the presence of neutrophils) may
increase risk.
• To facilitate early detection of neoplasia, patients are typically enrolled in
surveillance programs
• Patients with primary sclerosing cholangitis, enrolled for surveillance at the
time of diagnosis.
• Surveillance requires regular and extensive mucosal biopsy
• IBD-associated dysplasia; low-grade or high-grade.

68
Colitis-associated dysplasia;
(A) Dysplasia with extensive
nuclear stratification and
marked nuclear
hyperchromasia.
(B) Cribriform glandular
arrangement in high-grade
dysplasia.
(C)High-grade dysplasia on the
surface and underlying invasive
adenocarcinoma.
A large cysticinvasive
adenocarcinoma (arrow)
Small invasive glands
(arrowhead).

69
 SMALL INTESTINE AND COLON
• Intestinal Obstruction
– Hernias
– Adhesions
– Volvulus
– Intussusception
• Vascular Disorders of Bowel
– Ischemic Bowel Disease
– Angiodysplasia
• Malabsorption and Diarrhea
– Cystic Fibrosis
– Celiac Disease
– Environmental Enteric Dysfunction
– Autoimmune Enteropathy
– Lactase (Disaccharidase) Deficiency
– Microvillus Inclusion Disease
– Abetalipoproteinemia
• Infectious Enterocolitis
– Cholera
– Campylobacter Enterocolitis
– Shigellosis
– Salmonella
– Typhoid Fever
– Yersinia
– Escherichia coli
– Pseudomembranous Colitis
– Whipple Disease
– Viral Gastroenteritis
– Parasitic Enterocolitis
• Irritable Bowel Syndrome
• Inflammatory Bowel Disease (IBD)
– Crohn Disease
– Ulcerative Colitis
– Indeterminate Colitis
– Colitis-Associated Neoplasia
• Other Causes of Chronic Colitis
– Diversion Colitis
– Microscopic Colitis
• Graft-Versus-Host Disease
• Sigmoid Diverticular Disease
• Polyps
– Hyperplastic Polyps
– Inflammatory Polyps
– Hamartomatous Polyps
• Juvenile Polyps
• Peutz-Jeghers Syndrome
– Neoplastic Polyps
– Familial Adenomatous Polyposis
• Hereditary Non-Polyposis Colorectal Cancer
(HNPCC)
• Adenocarcinoma
• Anal Canal disorders
– Tumors of the Anal Canal
– Hemorrhoids
• Appendix
– Acute Appendicitis
70
– Tumors of the Appendix
 Diversion Colitis
• After surgical treatment of ulcerative colitis, Hirschsprung disease,
colon cancer, and other intestinal disorders
– A temporary or permanent ostomy, resulting in a blind distal
segment of colon from which the normal fecal flow is diverted.
• Diversion colitis can develop within the diverted segment.
– Development of numerous mucosal lymphoid follicles
– Increased numbers of lamina propria lymphocytes, monocytes,
macrophages, and plasma cells
– May resemble IBD; crypt abscesses, mucosal architectural
distortion, or, rarely, granulomas.
• Changes in the luminal microbiota and diversion of the fecal stream
that provides nutrients to colonic epithelial cells have been proposed.
• Diversion colitis resolves after anastomosis and restoration of fecal
flow.
71
 Microscopic Colitis
• Microscopic colitis encompasses two entities
– Collagenous colitis
– Lymphocytic colitis
• Chronic nonbloody, watery diarrhea without weight
loss.
• Findings on radiologic and endoscopic studies
typically are normal.
• Collagenous colitis: Middle-aged and older women
– The presence of a dense subepithelial collagen
layer
– Increased numbers of intraepithelial
lymphocytes
– A mixed inflammatory infiltrate within the
lamina propria
• Lymphocytic colitis: the subepithelial collagen layer is
of normal thickness
– the increase in intraepithelial lymphocytes
– associated with celiac and autoimmune diseases,
including thyroiditis, arthritis, and autoimmune
or lymphocytic gastritis.

72
Uncommon causes of colitis.
(A) Diversion colitis; large
lymphoid follicles with
germinal centers.
(B) Collagenous colitis with a
dense subepithelial collagen
band.
(C) Lymphocytic colitis.
Intraepithelial lymphocytes
can be recognized by their
densely stained, small nuclei.

73
 Irritable bowel syndrome (IBS)
• Chronic and relapsing abdominal pain, bloating, and changes in bowel habits
including diarrhea and constipation.
• IBS is currently divided into
– diarrhea-predominant,
– constipation-predominant, and
– mixed subtypes
• Pathogenesis; psychological stressors, diet, perturbation of the gut microbiome,
increased enteric sensory responses to GI stimuli, and abnormal GI motility.
• Diagnose; clinical criteria that require the occurrence of abdominal pain or
discomfort at least 3 days per month over 3 months with improvement following
defecation and a change in stool frequency or form
• No gross or microscopic abnormalities are found
• Between 20 and 40 years of age, a significant female predominance.
• The prognosis for IBS is most closely related to symptom duration, with longer
duration correlating with reduced likelihood of improvement.

74
 SMALL AND LARGE INTESTINES
• INTESTINAL OBSTRUCTION
• VASCULAR DISORDERS OF BOWEL
• DIARRHEAL DISEASE
• INFLAMMATORY INTESTINAL DISEASE
• COLONIC POLYPS AND NEOPLASTIC DISEASE
– Inflammatory Polyps
– Hamartomatous Polyps
– Hyperplastic Polyps
– Adenomas
– Familial Syndromes
– Adenocarcinoma

75
 COLONIC POLYPS AND NEOPLASTIC DISEASE
• Polyps are most common in the colon
but may occur in the esophagus,
stomach, or small intestine.
• Those without stalks are referred to as
sessile.
• Polyps with stalks are termed
pedunculated.
• Classified as nonneoplastic or
neoplastic.
– Neoplastic polyp; the adenoma,
has the potential to progress to
cancer.

– Non-neoplastic colonic polyps:

inflammatory, hamartomatous,
hyperplastic.
76
 Inflammatory Polyps
• The polyp that forms as part of the solitary
rectal ulcer syndrome
– The clinical triad of rectal bleeding,
mucus discharge, and an inflammatory
lesion of the anterior rectal wall.
• The underlying cause is impaired
relaxation of the anorectal sphincter,
creating a sharp angle at the anterior
rectal shelf.
– Recurrent abrasion and ulceration of
the overlying rectal mucosa.
• Chronic cycles of injury and healing
produce a polypoid mass made up of
inflamed and reactive mucosal tissue.

77
Solitary rectal ulcer syndrome
A, The dilated glands, proliferative epithelium, superficial erosions, and
inflammatory infiltrate are typical of an inflammatory polyp.
B, Epithelial hyperplasia.
C, Granulation tissue-like capillary proliferation within the lamina propria
caused by repeated erosion.

78
 Hamartomatous Polyps
• Hamartomatous polyps occur
– sporadically
– components of various genetically determined or acquired
syndromes
– Juvenile Polyps, Peutz-Jeghers syndrome
• Hamartomas; disorganized, tumor-like growths composed of mature cell
types normally present at the site at which the polyp develops.

• Hamartomatous polyposis syndromes are rare

– Associated intestinal and extraintestinal manifestations

– Screening of family members.

79
Gastrointestinal Polyposis Syndromes

80
 Juvenile Polyps

• The most common type of hamartomatous

polyp
• Sporadic or syndromic
• the sporadic form sometimes is also referred
to as an inflammatory polyp
• In children younger than 5 years of age
• Characteristically are located in the rectum
– Rectal bleeding
– Prolapse: protrudes through the anal
sphincter.
• Usually solitary
• The autosomal dominant syndrome of
juvenile polyposis; the number varies from 3
to as many as 100.
• Dysplasia occurs in a small proportion 81
 Juvenile Polyps - MORPHOLOGY

• Pedunculated, smooth surfaced, reddish

lesions
• Less than 3 cm in diameter
• Display characteristic cystic spaces on cut
sections.
• Microscopic examination; dilated glands
filled with mucin and inflammatory debris

82
 Peutz-Jeghers syndrome
• A rare autosomal dominant disorder
• Multiple gastrointestinal hamartomatous polyps
• Mucocutaneous hyperpigmentation
• An increased risk of several malignancies
– cancers of the colon, pancreas, breast, lung,
ovaries, uterus, and testes, as well as other unusual
neoplasms.
• Intestinal polyps are most common in the small
intestine
• May also occur in the stomach and colon and, rarely, in
the bladder and lungs.
• On gross evaluation, the polyps are large and
pedunculated with a lobulated contour.
• Histologic examination; arborizing network of
connective tissue, smooth muscle, lamina propria, and
glands
– Lined by normal-appearing intestinal epithelium.
83
 Hyperplastic Polyps

• Common epithelial proliferations

• In the sixth and seventh decades of life
• Result from decreased epithelial cell
turnover and delayed shedding of
surface epithelial cells, leading to a
“pileup” of goblet cells.
• No malignant potential
• Must be distinguished from sessile
serrated adenomas
– Histologically similar lesions that
have malignant potential

84
 Hyperplastic polyps - MORPHOLOGY
• Most commonly found in the left
colon
• Less than 5 mm in diameter
• Smooth, nodular protrusions of the
mucosa
• Often on the crests of mucosal folds
• Frequently multiple, particularly in
the sigmoid colon and rectum
• Histologically, hyperplastic polyps
are composed of mature goblet and
absorptive cells
– The delayed shedding, crowding
– The morphologic hallmark; the
serrated surface architecture
85
 Adenomas (Adenomatous Polyps)
• Neoplastic mass lesion
• Produce a mucosal protrusion, or polyp.
• The most common and clinically important neoplastic polyps are colonic adenomas
– Benign polyps that give rise to a majority of colorectal adenocarcinomas.
– Most adenomas do not progress to adenocarcinoma.
• Colorectal adenomas are characterized by the presence of epithelial dysplasia.
• Range from small, often pedunculated polyps to large sessile lesions.
• Present in nearly 50% of adults living in the Western world beginning age 50.
• Precursors to colorectal cancer,
– All adults undergo surveillance colonoscopy starting at age 50.
• Persons with a family history are at risk for developing colon cancer earlier in life
– Screened at least 10 years before the youngest age at which a relative was
diagnosed.
• Their frequency has risen as Western diets and lifestyles become more common.
86
 Adenomas (Adenomatous Polyps) - MORPHOLOGY
• Range from 0.3 to 10 cm in diameter and can be
pedunculated or sessile
• A texture resembling velvet or a raspberry, due to the
abnormal epithelial growth pattern
• Histologically, the cytologic hallmark of epithelial dysplasia
• Nuclear hyperchromasia, elongation, and stratification
• Most easily appreciated at the surface of the adenoma
• Pedunculated adenomas have slender fibromuscular stalks
containing prominent blood vessels derived from the
submucosa.
• The stalk usually is covered by non-neoplastic epithelium,
but dysplastic epithelium is sometimes present.

87
 Adenomas (Adenomatous Polyps) - MORPHOLOGY

• Adenomas can be classified as tubular,

tubulovillous, or villous on the basis of
their architecture.
• Tubular adenomas tend to be small,
pedunculated polyps composed of
small, rounded or tubular glands
• Villous adenomas, which often are
larger and sessile, are covered by
slender villi
• Tubulovillous adenomas have a
mixture of tubular and villous
elements
• Foci of invasion are more frequent in
villous adenomas than in tubular
adenomas 88
89
 Adenomas (Adenomatous Polyps) - MORPHOLOGY
• Sessile serrated adenomas overlap with
those of hyperplastic polyps and the typical
cytologic features of dysplasia are lacking
– Most common in the right colon, have a
malignant potential similar to that of
traditional adenomas.
• The most useful histologic feature is the
presence of serrated architecture
• Although most colorectal adenomas are
benign lesions, a small proportion may
harbor invasive cancer at the time of
detection.
• Size is the most important characteristic
that correlates with risk of malignancy.
90
91
 Familial Syndromes

• Several syndromes associated with colonic polyps

– Increased rates of colon cancer
• The genetic basis
• Familial adenomatous polyposis (FAP) and many others

92
Gastrointestinal Polyposis Syndromes

93
 Familial adenomatous polyposis (FAP)
• An autosomal dominant disorder marked by the appearance of numerous colorectal
adenomas by the teenage years
• Mutations of the adenomatous polyposis coli gene (APC)
• A count of at least 100 polyps is necessary for a diagnosis of classic FAP, and as many as
several thousand may be present
• Morphologically indistinguishable from sporadic adenomas.
• Colorectal adenocarcinoma develops in 100% of patients with untreated FAP, often
before age 30
• Prophylactic colectomy is standard therapy for persons carrying APC mutations.
• Patients remain at risk for extraintestinal manifestations
• Gardner syndrome; intestinal polyps, osteomas of mandible, skull, and long bones;
epidermal cysts; desmoid and thyroid tumors; and dental abnormalities, including
unerupted and supernumerary teeth.
• Turcot syndrome; intestinal adenomas and tumors of the central nervous system

94
Familial adenomatous polyposis.

Hundreds of small polyps are present throughout the colon

Three tubular adenomas in a microscopic field. 95

 Hereditary nonpolyposis colorectal cancer (HNPCC)
• Also known as Lynch syndrome
• Familial clustering of cancers at several sites; the colorectum,
endometrium, stomach, ovary, ureters, brain, small bowel, hepatobiliary
tract, and skin.
• Colon cancers occur at younger ages, located in the right colon
• Inherited germline mutations in genes that encode proteins responsible
for the detection, excision, and repair of errors that occur during DNA
replication
• At least five such mismatch repair genes
• Majority involve either MSH2 or MLH1.
• Characterized by microsatellite instability (MSI)

96
 Adenocarcinoma
• Adenocarcinoma of the colon is the most common malignancy of the
gastrointestinal tract
• A major contributor to morbidity and mortality worldwide.
• By contrast, the small intestine, which accounts for 75% of the overall
length of the gastrointestinal tract, is an uncommon site for benign and
malignant tumors.
– Among malignant small intestinal tumors, adenocarcinomas and
carcinoid tumors have roughly equal rates of occurrence, followed
by lymphomas and sarcomas.

97
 Adenocarcinoma - Epidemiology
• This represents nearly 15% of all cancer-related deaths, second only to
lung cancer.
• Colorectal cancer incidence peaks at 60 to 70 years of age, and less than
20% of cases occur before age 50.
• Males are affected slightly more often than females.
• Colorectal carcinoma is most prevalent in the United States, Canada,
Australia, New Zealand, Denmark, Sweden, and other developed
countries.
• The dietary factors associated with increased colorectal cancer rates; low
intake of unabsorbable vegetable fiber and high intake of refined
carbohydrates and fat.
• In addition to dietary modification, pharmacologic chemoprevention has
become an area of great interest.
• Several epidemiologic studies suggest that aspirin or other NSAIDs
have a protective effect. 98
 Adenocarcinoma - PATHOGENESIS
• Genetic and epigenetic
abnormalities
• At least two distinct genetic
pathways
• APC/β-catenin pathway
• The microsatellite instability
pathway, which is associated
with defects in DNA mismatch
repair
• Epigenetic events;
methylation-induced gene silencing
• APC is a key negative regulator of
β-catenin, a component of the
WNT signaling pathway
99
100
101
 Adenocarcinoma - Morphology
• Equally over the entire length of the colon
• In the proximal colon often grow as polypoid, exophytic masses
• In the distal colon tend to be annular lesions that produce “napkin-ring”
constrictions and luminal narrowing
• Both forms grow into the bowel wall over time.
• The general microscopic characteristics of right- and left-sided colonic
adenocarcinomas are similar.
– Mostly, well differentiated glands composed of tall columnar cells, that
resemble dysplastic epithelium. The invasive component elicits a strong
stromal desmoplastic response, their characteristic firm consistency.
– May be poorly differentiated tumors form few glands
– May, also, produce abundant mucin that accumulates within the intestinal
wall, with poor prognosis.
– May,also, be composed of signet-ring cells
– May display features of neuroendocrine differentiation.
102
103
104
Histologic appearance of colorectal carcinoma.
A, Well-differentiated adenocarcinoma. Note the elongated,
hyperchromatic nuclei. Necrotic debris, present in the gland lumen, is
typical.
B, Poorly differentiated adenocarcinoma forms a few glands but is
largely composed of infiltrating nests of tumor cells.
C, Mucinous adenocarcinoma with signet-ring cells and extracellular
mucin pools.

105
 Adenocarcinoma - Clinical Features
• Develop insidiously and may go undetected for long periods.
• Cecal and other right-sided colon cancers ; fatigue and weakness due to iron
deficiency anemia.
• Left-sided colorectal adenocarcinomas; occult bleeding, changes in bowel
habits, or cramping left lower quadrant discomfort
• The two most important prognostic factors; depth of invasion, the presence or
absence of lymph node metastases
• Staging; Originally recognized by Dukes and Kirklin
– Form the TNM (tumor-node-metastasis) classification
– Also, staging system from the American Joint Committee on Cancer.
• Metastases may involve regional lymph nodes, lungs and bones
– Because of the portal drainage, the liver is the most common site of
metastatic lesions
• The rectum does not drain by way of the portal circulation, and metastases from
carcinomas of the anal region often circumvent the liver.
106
Metastatic colorectal
carcinoma.
A, Lymph node metastasis.
Note the glandular structures
within the subcapsular sinus.
B, Solitary subpleural nodule
of colorectal carcinoma
metastatic to the lung.
C, Liver containing two large
and many smaller
metastases. Note the central
necrosis within metastases.

107
 SUMMARY-Colonic Polyps, Adenomas, and Adenocarcinomas
• Intestinal polyps; non-neoplastic or neoplastic.
– The non-neoplastic polyps; inflammatory, hamartomatous, or hyperplastic.
• Inflammatory polyps; a result of chronic cycles of injury and healing.
• Hamartomatous polyps; sporadically or as a part of genetic diseases
– Associated with increased risk of malignancy.
• Hyperplastic polyps; Benign epithelial proliferations, most commonly in the left colon and
rectum.
– No malignant potential
– Must be distinguished from sessile serrated adenomas.
• Adenomas; Benign epithelial neoplastic polyps
– The hallmark feature; cytologic dysplasia
– The precursors of colonic adenocarcinomas
• Sessile serrated adenomas; lack cytologic dysplasia, share morphologic features with hyperplastic
polyps.
• Familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC)
– the most common forms of familial colon cancer.
– FAP is caused by APC mutations, and patients typically have over 100 adenomas and
develop colon cancer before the age of 30.
– HNPCC; mutations in DNA mismatch repair genes. Fewer polyps, cancer at an older age
than FAP
– FAP and HNPCC are examples of two distinct pathways
• The two most important prognostic factors
– Depth of invasion
– The presence or absence of lymph node metastases. 108
 SMALL INTESTINE AND COLON
• Irritable Bowel Syndrome
• Intestinal Obstruction
– Hernias • Inflammatory Bowel Disease (IBD)
– Adhesions – Crohn Disease
– Volvulus – Ulcerative Colitis
– Intussusception – Indeterminate Colitis
– Colitis-Associated Neoplasia
• Vascular Disorders of Bowel • Other Causes of Chronic Colitis
– Ischemic Bowel Disease – Diversion Colitis
– Angiodysplasia – Microscopic Colitis
• Malabsorption and Diarrhea • Graft-Versus-Host Disease
– Cystic Fibrosis • Sigmoid Diverticular Disease
– Celiac Disease • Polyps
– Environmental Enteric Dysfunction – Hyperplastic Polyps
– Autoimmune Enteropathy – Inflammatory Polyps
– Lactase (Disaccharidase) Deficiency – Hamartomatous Polyps
– Microvillus Inclusion Disease • Juvenile Polyps
– Abetalipoproteinemia • Peutz-Jeghers Syndrome
• Infectious Enterocolitis – Neoplastic Polyps
– Cholera • Familial Adenomatous Polyposis
– Campylobacter Enterocolitis • Hereditary Non-Polyposis
– Shigellosis • Colorectal Cancer (HNPCC)
– Salmonella
– Typhoid Fever • Adenocarcinoma
– Yersinia • Anal Canal disorders
– Escherichia coli – Tumors of the Anal Canal
– Pseudomembranous Colitis – Hemorrhoids
– Whipple Disease
– Viral Gastroenteritis • Appendix
– Parasitic Enterocolitis – Acute Appendicitis
– Tumors of the Appendix 109
 THE ANAL CANAL
• The upper zone is lined by
columnar rectal epithelium;
• The middle third by
transitional epithelium;
• The lower third by stratified
squamous epithelium.

110
TUMORS OF THE ANAL CANAL
• Glandular or squamous patterns of
differentiation SCC

• Basaloid SCC; An additional

differentiation pattern of squamous cell
carcinomas
– Tumors populated by immature cells Anal SCC
derived from the basal layer of with
transitional epithelium basaloid
features
– Archaic term cloacogenic carcinoma
– Basaloid differentiation may be
mixed with mucinous differentiation
– With infection by high-risk strains of Condyloma
human papilloma virus (HPV) acuminatum
with
verrucous
architecture
111
 Hemorrhoids

• Hemorrhoids affect about 5% of the

general population.
• Dilated anal and perianal collateral
vessels
• More common and less serious than
esophageal varices
• Common factors that predispose
• Constipation
• Increased intra-abdominal and
venous pressures: venous stasis of
pregnancy
• Portal hypertension.

112
 Hemorrhoids - MORPHOLOGY
• Below the anorectal line and are
termed external hemorrhoids
• Within the distal rectum are referred
to as internal hemorrhoids
• On histologic examination:
thin-walled, dilated, submucosal
vessels
• Subject to trauma and tend to become
inflamed, thrombosed, and, in the
course of time, recanalized.
• Superficial ulceration may occur

113
 APPENDIX
• ACUTE APPENDICITIS
• TUMORS OF THE APPENDIX

114
 APPENDIX
• The appendix is a normal true
diverticulum of the cecum.

• Prone to acute and chronic

inflammation

• Acute appendicitis is a relatively

common entity.

• Other lesions, including tumors, can

also occur in the appendix but are far
less common.

115
 ACUTE APPENDICITIS
• Initiated by intraluminal pressure that compromises venous outflow.
• Associated with overt luminal obstruction; fecalith, gallstone, tumor, mass of
worms
• The condition may be confused with
– mesenteric lymphadenitis (often secondary to unrecognized Yersinia
infection or viral enterocolitis)
– acute salpingitis
– ectopic pregnancy,
– mittelschmerz (pain associated with ovulation)
– Meckel diverticulitis
• In early acute appendicitis, subserosal vessels are congested, and a modest
perivascular neutrophilic infiltrate is present within all layers of the wall.
• Diagnosis of acute appendicitis requires neutrophilic infiltration of the
muscularis propria.
• In more severe cases, focal abscesses may form within the wall (acute
suppurative appendicitis)
• May even progress to large areas of hemorrhagic ulceration and gangrenous
necrosis that extend to the serosa, creating acute gangrenous appendicitis,
which often is followed by rupture and suppurative peritonitis
116
117
 ACUTE APPENDICITIS - Clinical Features
• Typically, early acute appendicitis produces periumbilical pain
• Ultimately localizes to the right lower quadrant, followed by
nausea, vomiting, low-grade fever, and a mildly elevated peripheral
white cell count.
• A classic physical finding is McBurney’s sign; deep tenderness
noted at a location two thirds of the distance from the umbilicus to
the right anterior superior iliac spine (McBurney’s point).

• These signs and symptoms often are absent, creating difficulty in

clinical diagnosis.

118
 TUMORS OF THE APPENDIX
• The most common tumor of the appendix is the carcinoid
• Discovered incidentally at the time of surgery or on examination of a
resected appendix.
– The distal tip of the appendix
– It produces a solid bulbous swelling up to 2 to 3 cm in diameter.
• Conventional adenomas or non–mucin-producing adenocarcinomas also
occur in the appendix
• Mucocele, a dilated appendix filled with mucin, may simply stem from an
obstructed appendix containing mucin
– May be a consequence of mucinous cystadenoma or mucinous
cystadenocarcinoma.
– Invasion through the appendiceal wall can lead to intraperitoneal
seeding and spread.
– In women, the resulting peritoneal implants may be mistaken for
mucinous ovarian tumors.
– In the most advanced cases, the abdomen fills with mucin, a condition
called pseudomyxoma peritonei
119
 Peritoneal Cavity
• Houses the abdominal viscera
• Lined by a single layer of mesothelial
cells
– Cover the visceral and parietal
surfaces, supported by a thin
layer of connective tissue to
form the peritoneum
• Diseases included in the peritoneal
cavity and retroperitoneal space
may be
– Inflammatory
– Infectious
– Neoplastic disorders
120
 INFLAMMATORY DISEASE
• Peritonitis may result from bacterial invasion or chemical irritation and is
most often due to:
– Leakage of bile or pancreatic enzymes, which produces sterile
peritonitis.
– Perforation or rupture of the biliary system that evokes a highly irritating
peritonitis, usually complicated by bacterial superinfection
– Acute hemorrhagic pancreatitis, which is associated with leakage of
pancreatic enzymes and fat necrosis. Damage to the bowel wall may
allow bacteria to spread to the peritoneal cavity.
– Foreign material, including that introduced surgically (e.g., talc and
sutures), may induce foreign body–type granulomas and fibrous scarring.
– Endometriosis, which causes hemorrhage into the peritoneal cavity, that
acts as an irritant.
– Ruptured dermoid cysts, which release keratins and induce an intense
granulomatous reaction.
– Perforation of abdominal viscera, which results in leakage of luminal
materials that can lead to infection and immune activation.
121
 Peritoneal Infection
• Bacterial peritonitis; bacteria from the GI lumen, most commonly intestinal
perforation.
– E. coli, streptococci, S. aureus, enterococci, and C. perfringens; most often.
• Spontaneous bacterial peritonitis develops in the absence of an obvious source of
contamination.
– In patients with cirrhosis and ascites
– Less frequently in children with nephrotic syndrome
• Diagnosis; the presence of neutrophils in ascitic fluid and positive bacterial cultures
– E. coli, streptococci, and Klebsiella species are the most frequently involved
organisms.
• The cellular inflammatory response;
– Dense collections of neutrophils, fibrinopurulent debris
– Subhepatic and subdiaphragmatic abscesses may be formed.
• With the exception of tuberculous peritonitis, the reaction usually remains
superficial.
122
 Sclerosing Retroperitonitis
• Sclerosing retroperitonitis; idiopathic retroperitoneal fibrosis or Ormond
disease
– Characterized by dense fibrosis that may extend to involve the
mesentery
• The cause of sclerosing retroperitonitis is unknown
• Some are defined as IgG4-related sclerosing disease
– An immunoinflammatory disorder that can lead to fibrosis in a wide
variety of tissues.
• The process frequently compresses the ureters

123
 TUMORS OF PERITONEAL CAVITY
• Mesothelioma; Primary malignant tumors arising from the peritoneal
lining
– Similar to tumors of the pleura and pericardium.
– Almost always associated with high levels of asbestos exposure.
• Rarely, primary benign and malignant soft tissue tumors
• Desmoplastic small round cell tumor
– An aggressive tumor in children and young adults.
– A strong morphological resemblance to Ewing sarcoma
– Characterized by a reciprocal translocation, t(11;22) (p13;q12), that
produces a EWS and WT1 fusion gene.
• Secondary tumors: direct spread or metastatic seeding,
– Peritoneal carcinomatosis (peritonitis carcinomatosa)
– Pseudomyxoma peritonei; caused by mucinous carcinomas,
particularly those of the appendix. 124