Small & large intestine

Small & large intestine

Diseases of intestine-
• Developmental anomalies
• Inflammatory bowel disease
• Benign tumors
• Malignant tumors
• Malabsorption syndrome
• Infectious enterocolitis
 Developmental anomalies
• Developmental anomalies are uncommon but
sometimes result in serious disease.
they are
1)Meckel diverticulum
2)Hirschsprung’s disease
 Developmental anomalies
• 1)Meckel diverticulum is a vestigial remnant of
the omphalomesenteric duct (also called the vitelline
duct ), and is the most frequent malformation of
the gastrointestinal tract.
• In the human embryo, the vitelline duct, also known
as the omphalomesenteric duct, is a long narrow
tube that joins the yolk-sac to the midgut lumen of
the developing fetus
• Meckel's diverticulum is located in the distal ileum,
usually within about 60-100 cm of the ileocecal valve
 Meckel diverticulum
•  Rule of 2's: 2% (of the population) - 2 feet
(from the ileocecal valve) - 2 inches (in length)
- 2% are symptomatic, there are 2 types of
common ectopic tissue (gastric and
pancreatic), the most common age at clinical
presentation is 2, and males are 2 times as
likely to be affected. However, the exact value
for the above criteria range from 0.2-5 (for
example, prevalence is probably 0.2-4%)
Meckel diverticulum
 Meckel diverticulum
• They are composed of all layers of the normal
small intestine.
• Sometimes heterotopic islands of gastric
mucosa are there.
• Peptic ulceration can occurs in the adjacent
mucosa.
 Meckel diverticulum
• The majority of people afflicted with Meckel's
diverticulum are asymptomatic. If symptoms do
occur, they typically appear before the age of two.

• The most common presenting symptom is

painless rectal bleeding, followed by intestinal
obstruction, volvulus and intussusception.
Occasionally, Meckel's diverticulitis may present with
all the features of acute appendicitis
 A volvulus is a bowel
obstruction in which a loop
of bowel has abnormally
twisted on itself

An intussusception is
condition in which a part of
the intestine
has invaginated into another
section of intestine
 Hirschsprung’s disease
• Hirschsprung’s disease is a congenital disorder of the colon in
which ganglion cells are absent in the small segment of large
intestine, causing chronic constipation, an  enlargement of
the colon, caused by bowel obstruction.
• An aganglionic segment is formed that lacks both the
Meissner submucosal & myentric plexuses.
• This causes functional obstruction & progressive distention of
the colon proximal to the affected segment.
• Colon becomes massively distended , some times achieving a
diameter of 15 to 20 cm.
Hirschsprung’s disease
 Hirschsprung disease
Massively distended colon

Clinical feature
1) Delayed passage of
 meconium.
2) Abdominal distension.
3) Constipation
 Hirschsprung disease
• Treatment of Hirschsprung's disease consists
of surgical removal (resection) of the
abnormal section of the colon, followed by
reanastomosis.
 Inflammatory bowel disease (IBD)
• Inflammatory bowel disease (IBD) is a group
of inflammatory conditions of the colon and small intestine
• The main forms of IBD are Crohn's disease and ulcerative
colitis (UC).
other forms of IBD:
• Collagenous colitis
• Lymphocytic colitis
• Ischaemic colitis
• Diversion colitis
• Behçet's syndrome
• Indeterminate colitis
 IBD
• The main difference between Crohn's disease and UC is the
location and nature of the inflammatory changes.

• Crohn's disease can affect any part of the gastrointestinal

tract, from mouth to anus (skip lesions), although a majority
of the cases start in the terminal ileum. Ulcerative colitis, in
contrast, is restricted to the colon and the rectum.

• Microscopically, ulcerative colitis is restricted to the mucosa ,

while Crohn's disease affects the whole bowel wall
 IBD
• Pathogenesis of IBD- It involves
• 1) Genetic predisposition
• 2)Immunologic factors
• 3) Microbial factors
• 1) Genetic predisposition:
• First –degree relatives are 3 to 20% times more likely to
develop the disease.
• Ulcerative colitis has been associated with HLA-DRB1 gene
• HLA-DR7 & DQ4 alleles are associated with Crohn disease.
• Non HLA gene NOD2 is mutated in 25% of Crohn disease Pt.
• Mutant form of the IL-23 receptor (IL23R) gene has been
recently found in both the diseases .
• IL-23 is a cytokine that promotes the production of IL-17 by T-
cells.
• It is not known how mutant genes influence immunologic
response,
 IBD
• 2) Immunologic factors-
• Tissue inflammation may be the result of secretion of
cytokine IL-17 by CD4T cells.
• TNF may play important pathogenic role in Crohn
disease because the effectiveness of treatment with
TNF antagonist in this disorder.
• Perinuclear antineutrophil cytoplasmic antibodies
are present in 75% of persons with ulcerative colitis
& only 11% of Pt with Crohn disease.
 IBD
• 3) Microbial factors:
• There is no evidence that these diseases are caused
or trigger by microbes
• Microbes may provide the antigenic trigger to
deregulated immune system.
• Inflammation is the final common pathway for the
pathogenesis of IBD.
•
 Crohn disease
• Crohn disease must be viewed as a systemic
inflammatory disease with predominant
gastrointestinal involvement.
• Extra –intestinal complicaton are of immune
origin such as uveitis, sacroilitis, migratory
polyartheritis, erythema nodosum, bile duct
inflammatory disorders & obstructive
uropathy with stone formation etc.
 Crohn disease
Epidemiology
- Much more prevalent in USA ,Great Britain &
Scandinavia.
- Peak incidence is between the second & third
decades of life.
- Females are slightly more affected
- Whites are more affected then nonwhites
- 3 to 5 times more often in jews.
 Crohn disease
• Morphology –When fully developed , Corhn disease
is characterized by-
• 1) Trans mural inflammatory process of bowel with
mucosal damage.
• 2) Presence of noninflammatory granuloma
• 3) Fistula formation.
• Small intestine alone involves in 30%
• Small + Large intestine- 40%
• Colon alone in 30%
 Crohn disease
• Sharp demarcation of diseased bowel
segment form adjacent uninvolved bowel
(skip lesion).
- The intestinal wall is rubbery & thick-edema,
inflammation, fibrosis, hypertrophy of
muscularis propria.
-long serpentine ulcers & narrow fissures
developed in affected bowel segment
Gross - ileum:  The fibrous reparative reaction in Crohn
disease causes marked thickening of the bowel wall and
stenosis of the lumen (Rubber hose or lead pipe bowel)
 IBD
• Crohn disease—biopsy from
a terminal ileum with active
disease. The figure illustrates
a discrete granuloma
composed of compact
macrophages, and
epithelioid cells, but there is
no necrosis.
Crohn’s disease- fissure
Crohn’s disease

Multiple Non-caseating
granulomas in the colon
 Crohn disease

This upper GI series

reveals a proximal
and a distal
segmental area of
stricture in the
terminal ileum,
consistent with
Crohn's disease
Pyoderma gangrenosum on the Erythema nodosum on the back
leg of a person with Crohn's of a person with Crohn's
disease disease
 Crohn disease
• Extension of fissures leads to fistula or sinus
tract formation, to adherent viscera, to
outside skin,or into a blind cavity to form a
localized abscess.
 Crohn disease
Microscopic appearance-
• Inflammation ,with netrophilic infiltration &
formation of crypt abscesses.
• Ulceration
• Mucosal atrophy & metaplasia
• Noncaseating granuloma present
• Lymphocytic aggregates.
• Five to six fold increased risk of carcinoma
,particularly of the colon.
 Crohn disease
Clinical features-
• The dominant manifestations are diarrhea, abdominal pain &
fever.
• Melena is present in about 50% of cases with colon
involvement.
Complications-
• Fistula formation-other loop of bowel, urinary bladder,
vagina, perianal skin .
• Rare complications-massive bleeding, toxic dilatation of colon
or small intestine & carcinoma
 Treatment
• Currently there is no cure for Crohn's disease
and remission may not be possible or prolonged if achieved
• Acute condition- medications to treat any infection and to
reduce inflammation (normally aminosalicylate anti-
inflammatory drugs and corticosteroids).
• Low doses of the opiate receptor antagonist -Naltrexone have
been found to be effective in inducing remission in 67% of
patients with Crohn's disease - in a small study conducted at
Pennsylvania State University
 Ulcerative colitis
• UC is an ulceroinflammatory disease affecting
the colon.
• It is limited to the mucosa & submucosa
except in the most severe case.
• It begins in the rectum & extends proximally
in a continuous fashion.
• It is a systemic disorder in some Pt.
 Ulcerative colitis
• There are several important differences
between ulcerative colitis& crohn diseases-
• Granulomas are absent
• No skip lesion
• Mucosal ulcer rarely extend below the
submucosa.
• Mural thickening ,fibrosis are absent
• High risk of developing carcinoma.
 IBD

Ulcerative colitis—colonic
mucosal biopsy taken from
a patient with active
disease. The crypt abscess
is composed of
transmigrated neutrophils
and the surrounding
epithelium exhibits features
of acute mucosal injury.
 Ulcerative colitis
Epidemiology –
• More common then Crohn disease.
• More common in white people
• Peak incidence is between 20 to 25 years.
• Increase frequency of ankylosing spondilitis in
individual with HLA-b27 allele & UC.
 Ulcerative colitis
• Morphology
Colonic involvement is continuous from the distal
colon from rectum to sigmoid & may involve the
entire colon.
• Skip lesion are absent
• With severe disease , there is broad based
ulceretion ,hyperemia, edema present.
• Isolated islands of regenerating mucosa bulge
upward to create pseudopolyps.
• In rare cases pericolonic abscess are formed.
 Ulcerative colitis
• Some times complete shutdown of
neuromuscular function with toxic megacolon.
Ulcerative colits- Pseudopolyps.

The photo above shows

a inflammatory
pseudopolyps.
This does look a case of
familial adenomatous
polyposis, but
microscopically there
was no adenomatous or
otherwise dysplastic
change anywhere in the
whole colon
 Ulcerative Colitis
• Ulcerative Colitis: is an
inflammatory bowel disease
similar to Crohn’s disease.

• It virtually always involves the

rectum and presents with small
ulcerations and a tubular
appearance to the colon
 Ulcerative colitis
Microscopic appearance-
• Mononuclear inflammatory infiltrate in the lamina
propria is present.
• Mucosal & submucosal ulcer & Crypt abscess.
• With remission granulation tissue fills in the ulcer
craters, followed by regeneration of mucosal
epithelium.
• Submucosal fibrosis,mucosal atrophy remain as
residua of healed disease.
 Ulcerative colitis
Complication:
-Development of colon carcinoma
Two factor govern the risk-
1) Duration of disease
2) Anatomical extension of lesion.
- Overall , the annual incidence of colon cancer in person with
UC of more then 10 years duration is 0.8 to 1%.
- Pt may have DNA repair defect in mucosal cells throughout
the intestine.
 Ulcerative colitis
Clinical features-
It is chronic relapsing disorder marked by
1)Mucoid, bloody diarrhea
2) Cramps, tenesmus & lower abdominal pain that is relieved by
defecation
3) In some Pt. fever & weight loss.
4) Symptoms may persist for days,weeks or months & then
subsides.Disease recure after interval of months to year or
even decades.
5) Extra-intestinal manifestations are more common in UC then
crohn disease.
 Extraintestinal features of UC

• As ulcerative colitis is believed to have

a systemic (i.e., autoimmune) origin, patients may
present with symptoms and complications outside
the colon. These include the following:
• aphthous ulcers of the mouth
• Ophthalmic-
– Iritis or uveitis
– Episcleritis
 Extraintestinal features of UC

• Musculoskeletal:Seronegative arthritis, which can be a large-

joint oligoarthritis or may affect many small joints of the
hands and feet
• Ankylosing spondylitis, arthritis of the spine
• Sacroiliitis, arthritis of the lower spine
• Cutaneous : Erythema nodosum, which is a panniculitis, or
inflammation of subcutaneous tissue involving the lower
extremities
• Pyoderma gangrenosum, which is a painful ulcerating lesion
involving the skin
 Extraintestinal features of UC
• Deep venous thrombosis and pulmonary
embolism
• Autoimmune hemolytic anemia
• clubbing, a deformity of the ends of the
fingers
 Treatment
• Medications treating ulcerative colitis include
1) Anti-inflammatory agents such as 5-ASA
(5-aminosalicylic acid) compounds, systemic
corticosteroids, topical corticosteroids.
• 2) Immunosuppressants 
•  azathioprine,  methotrexate , cyclosporine 
 Surgery
• Surgery for ulcerative colitis & Crohn disease
usually involves removing diseased intestine
or the entire colon and the rectum.
• Removal of the colon and rectum is the only
permanent cure for ulcerative colitis. This
procedure also eliminates the risk of
developing colon cancer.
 Tumor of the small & large
intestine
• Classification-
1) Non-neoplastic polyp-
• Hyperplastic polyp
• Hamartomatous polyp
• Peutz-Jeghers polyp
• Inflammatory polyp
• Lymphoid polyp
 Tumors of Intestine
2) Neoplastic Epithelial lesions
• Benign polyps
Adenoma
• Malignant lesion
Adenocarcinoma
Squmous cell carcinoma of the anus.
3) Other tumors-
Stromal tumor
Carcinoid tumor
Lymphoma.
 Tumors of intestine
• Polyp is mass that protrudes into the lumen of the
gut.
• Non-neoplastic polyps-Arise as a result of abnormal
mucosal maturation or inflammation & do not have
malignant potential.
• Adenomatous polyps-arise as the result of epithelial
proliferation & dysplasia. They are precursors of
carcinoma.
 Non-neoplastic polyp
• Non neoplastic polyps represent about 90% of all epithelial
polyp in large intestine.
• Age- More common after 60 year.
• More common in the rectosigmoid region
Inflammatory polyp-
• These are polyps which are associated with inflammatory
conditions such as Ulcerative Colitis and Crohns disease
 Polyps of Intestine
Hamartomatous polyp-
They are growths, like tumours found in organs
as a result of faulty development.
They are normally made up of a mixture of
tissues. They grow at the normal rate of the
host tissue and rarely cause problems such as
compression.
 Peutz–Jeghers syndrome
Peutz–Jeghers syndrome,
also known as hereditary
intestinal polyposis syndrome,
is an autosomal
dominant genetic disease
characterized by the
development of benign
hamartomatous polyps in the
gastrointestinal tract and
hyperpigmented macules on
the lips and oral mucosa
Peutz–Jeghers
syndrome

Mucocutaneous
melanotic lesions
 Adenoma
• Adenoma-all adenomatous lesions arise as the
result of epithelial proliferation & dysplasia.
• Incidence of adenoma in the small intestine is
very low.
• Prevalence of colonic adenoma is 20% to 30%
before age 40.
• 40% to 50% after age of 60.
 Adenoma
• On the basis of the epithelial architecture four
subtypes are observed-
• 1) Tubular adenoma
• 2) Villlous adenoma
• 3) Tubulovillous adenoma
• 4) Sessile serrated adenoma
 Tubular adenoma
• 1) Tubular adenoma -
• An adenoma whose cells are arranged in
tubules.
• Most common polyp & cancer is rare in this
type of adenoma.
• Reach up to the 2.5 cm in diameter
• Most often found in rectosigmoidal region.
 Tubular adenoma

 The image shows a

pedunculated tubular
adenoma with glands lined
by tall, crowded,
hyperchromatic epithelial
cells
 Villous adenoma
Villous adenomas-
•  The villous pattern presents villi - finger-like
projections lined by dysplastic epithelium and
with thin fibro-vascular core.
• They are larger & sessile.
• Invasive carcinoma is found in as many as 40%
of this lesion.
• They reach up to 10 cm in diameter
 villous adenoma

The gross appearance of

a villous adenoma is
shown above the surface
at the left, and in cross
section at the right. Note
that this type of adenoma
is sessile, rather than
pedunculated, and larger
than a tubular adenoma.
 Villous adenoma

Histology of villous
adenoma. Fingerlike
projections stretching
from the surface of a
polyp downward with
minimal branching.
 3)Tubulovillous adenoma
They are composed of a
broad mix of tubular &
villous areas

•A partly sessile polyp is

present in the cecum
adjacent to the Ileolcecal
Valve. 
 Sessile serrated adenomas-
• Sessile serrated adenomas- They are
characterized by serrated epithelium lining in
the crypts.
• They are hyperplastic polyps , may have
malignant potential
 Sessile serrated adenomas (SSA)
Microscopy
SSAs are characterized
by:
-basal dilation of the
crypts,
-basal crypt serration,
-crypts that run
horizontal to the
-basement membrane
(horizontal crypts), and
crypt branching
 Polyps
Clinical features:
• Smaller adenomas are usually asymptomatic.
• Villous adenomas – cause rectal bleeding
- Secrete sufficient amount of mucoid material
rich in protein & potassium to produce
hypoproteinemia or hypokalemia.
- All adenomas are to be considered potentially
malignant .
- Prompt & adequate excision is mandated.
 Colorectal carcinoma
• About 5% of Americans will develop colorectal
carcinoma.
• Nearly 15% of all cancer-related deaths accounts for
this disease.
• About 134,000 new cases diagnosed & 55000 deaths
occur in USA per year.
• The small intestine is an uncommon site for benign
or malignant tumors.
• They almost always arise in adenomatous polyps that
are curable by resection.
 Colorectal carcinoma
Epidemiology-
• Peak incidence for carcinoma is 60 to 70 year of age.
• Adenomas are the precursor lesion for most of the
tumor.
• Male are 20% more often affected.
• Highest incidence rate in the USA, Canada, Australia
New Zealand & other developed countries.
 Colorectal carcinoma
• Dietary factors that leads to develop CA are-
• Low unabosorbable vegetable fibers
• High content of refined carbohydrate & meat fat
• High fat intake enhances the synthesis of cholesterol and bile
acids by the liver, which in turn may be converted into
potential carcinogens by intestinal bacteria.
• Refined diets also contain less of vitamins A, C, and E, they
are
protective microneutrient
 Colorectal carcinoma
• Low dietary fibers leads to decreased stool
bulk & increased fecal retention in the bowel
& altered bacterial flora.
• Toxic oxidative byproduct(Carcinogens)
produced by bacteria from Refined
carbohydrate .
 Colorectal carcinoma
• NSAID & Aspirin exerts a protective effect
against carcinoma via inhibition of
cyclooxygenase 2(COX-2).Enzyme
overexpressed in 90% of colorectal carcinoma.
• The risk of cancer is directly related to the
number & size of adenomas.
 Colorectal carcinoma
Carcinogenesis-
• There are two pathways for development of
colon cancer.
• 1)APC/Beta catenin pathway
• 2) The mismatch repair pathway
(Microsatellite instability)
 Beta catenin
• Beta-catenin is a protein that in humans is
encoded by the CTNNB1 gene.
• β-catenin is part of a complex of proteins that
constitute adherens junctions (AJs).
• AJs are necessary for the creation and
maintenance of epithelial cell layers by
regulating cell growth and adhesion between
cells
 Adenomatous polyposis coli gene
(APC gene)
• 1) APC/ beta catenin pathway-
• APC gene produces the APC Protein
• APC protein is responsible for destruction of Beta-catenin.
• With loss of APC gene ,Beta catenin is not destroyed & it
translocates to the nucleus.
• In the nucleus it activate the transcription of several genes
such as MYC & cyclin D1.
• Gene promote cell proliferation, adenoma & cancer
formation.
• This adenoma carcinoma sequence, account for about 80% of
sporadic colon carcinoma.
 Colorectal carcinoma
Mismatch repair path way-
• This pathway is involved in 10% to 15% of sporadic
case of cancer.
• There are five DNA repair genes-
MSH2,MSH6,MLH1,PMS1 & PMS2
• Inherited mutations in one of the five genes give rise
to the hereditary nonpolyposis colon carcinoma.
• MLH1 & MSH2 are the most commonly involved in
mutation.
 Colorectal carcinoma
Mismatch repair path way(Continue)-
Loss of these genes lead to unstable DNA
replication sequence – called microsatellite
instability (MSI).
This pathway is often referred to as the MSI
pathway.
 Colorectal carcinoma
Morphology-
• 25% Of CA are in cecum & ascending colon
• 25% in rectum & distal sigmoid.
• 25% in descending colon & proximal sigmoid.
• Remainder are scattered else ware.
• Lesion may be solitary or multiple.
• Tumor in the proximal colon tend to grow as polypoid,
exophytic mass-obstruction is uncommon.
• Carcinoma in the distal colon tend to be annular-encircling
lesions-obstruction is common.
 Colorectal carcinoma

This cancer is more exophytic in its growth

pattern.
 Colorectal carcinoma
• An encircling
adenocarcinoma of the
rectosigmoid region is
seen here. This produces
the occult bleeding.

• The tumor encircles the

colon and infiltrates into
the wall.
• The barium enema Colorectal carcinoma
technique instills the
radiopaque barium sulfate
into the colon, producing a
contrast with the wall of the
colon that highlights any
masses present.

• In this case, the classic

"apple core" (arrow)lesion
is present, representing an
encircling adenocarcinoma
that constricts the lumen.
 CT Colonography with Intravenous Contrast Material

Axial 2D images show a

circumferential mass of
the transverse colon
(arrows) with an
enlarged, necrotic
pericolonic lymph node
 Colorectal carcinoma
• Microscopic appearance of both the
carcinoma are similar.
• Changes range from well-defferentiated to
undifferentiated adenocarcinoma.
• Many tumor produce mucin.
 Adenocarcinoma of colon

The edge of the carcinoma

arising in the adenoma is
seen here.

The neoplastic glands are

long and frond-like, similar
to those seen in a villous
adenoma.

The growth is primarily

exophytic and invasion is
not seen at this point.
 Adenocarcinoma of colon

Microscopically, a
moderately differentiated
adenocarcinoma of colon
is seen here. There is still
a glandular configuration,
but the glands are
irregular and very
crowded. Many of them
have lumens containing
bluish mucin.
 Colorectal carcinoma
Clinical features-
• Right sided lesions produce fatigue, weakness & iron
deficiency anemia.
• Left sided tumor may produce occult bleeding,
changes in bowel habit & abdominal discomfort.
• Iron deficiency anemia in an older man means G.I.
tract cancer until proved otherwise.
 Colorectal carcinoma
• Spread : Directly extension into adjacent
structure.
• Metastatics - in the lymph nodes, serosa,
peritoneal cavity, liver, lung & bones.
•
 Colorectal carcinoma
Diagnosis-
• Occult blood test.
• Sigmoidoscopy, colonoscopy with biopsy,
• Tumor marker like CEA are of little diagnostic value.
• APC mutation occur early in most CA.
• Detection of mutant APC in epithelial cells isolated
from stools ,is evaluated as diagnostic test.
 Colorectal carcinoma
Treatment-
• Surgery & chemotherapy.
• When cancer is caught at early stage, it can be
curable.
• With distant metastasis it is less likely to be
curable.
 Neoplasm of small intestine
• Small intestine accounts for Only 3% to 6% of
GI tract tumors.The most frequent benign tumors in the small
intestine are stromal tumors.Small intestine adenocarcinoma
& carcinoid have a equal incidence.
Small intestine tumors-
1) Stromal tumors-Leiomyoma, lipoma, neurogenic & vascular
tumors .
2) Epithelial tumors- Adenoma & adinocarcinoma
3) Carcinoid.
 Neoplasm of small intestine
• Adenocarcinoma of small intestine:
• These tumors grow in a manner similar to
colonic cancer.
• Most small bowel carcinoma arise in the
duodenum.
• Adenoma in the vicinity of the ampulla of
vater may produce biliary obstruction &
obstructive jaundice.
 Other tumors of G.I. tract
• They are
• 1)Gastrointestinal stromal tumors
• 2)Gastrointestinal lymphoma
• 3) Carcinoids
 Gastrointestinal stromal tumors
(GISTs)-
• Gastrointestinal stromal tumors (GISTs)- They
are benign leiomyoma or malignant
leiomyosarcoma.
• Most GISTs occurs in adults.
• Malignant tumor metastasized in liver,
peritoneum & lungs.
• Common site- stomach , but can be present in
small & large intestine.
 Gastrointestinal lymphoma

• G.I. tract lymphoma can be 1) Primary or

2)secondary
1) Primary G.I. tract lymphoma reveal no evidence of
liver, spleen or bone marrow involvement at the
time of diagnosis.
2) Any segment of G.I. tract may involved secondarily
by systemic non-Hodgkin lymphomas.
• G.I.tract is the most common extra nodal location.
• 1 to 4% of all G.I. tract malignancy are lymphoma.
 Gastrointestinal lymphoma

Most common form in western countries is Mucosa associated

lymphoid tissue(MALT) lymphoma.
• Site- Stomach 55% to 60%
Small intestine 25 % to 30%
Colon 10 to 15 %.
- Gastric MALT lymphomas arise as a result of Helicobactor
associated chronic gastritis.
50% of gastric lymphoma can regress with antibiotic treatment
for H.pylori.
-Celiac disease is associated with a higher than normal risk of
intestinal T-cell lymphomas.
 Non-Hodgkin's lymphoma- gross

Non-Hodgkin's lymphomas of the bowel do occur uncommonly.

The multifocal irregular tan-to-brown masses seen here on the
mucosal surface are in a patient with AIDS..
Non-Hodgkin's lymphoma

The large blue non-Hodgkin's lymphoma Malignant lymphoid tumor of the

cells can be seen infiltrating through the stomach composed of large lymphoid
mucosa cells, mainly of B-cell type
 Gastrointestinal lymphoma
• Primary G.I. Tract lymphoma generally have a
better prognosis then do those arising in other
sites.
• Gastric lymphoma those that do not regress
with antibiotic treatment usually contain the
t(11:18) translocation or other genetic
abnormalities.
 Neuroendocrine cells of stomach 

• Neuroendocrine
cells (neurosecretory
cells)are cells that
receive neuronal input
(neurotransmitters
released by nerve cells)
and, as a consequence of
this input, release
hormones to the blood.
Neuroendocrine cells
help control the release
of digestive juices
 Carcinoids
• Carcinoid is the term used to describe a well to
moderately differentiated neuroendocrine tumor in
the stomach, intestine, appendix, rectum, and lung
- Carcinoid tumors start from cells of neuroendocrine
system.
• This system consists of cells that are like nerve cells
in certain ways and like hormone-making endocrine
cells in other ways.
• They are scattered throughout other organs like the
pancreas, and lungs.
• Carcinoid tumors most often start in the digestive
system.
 Carcinoids
• The appendix is the most common site of gut
carcinoid tumor followed by the small intestine,
rectum, stomach & colon.
• They appear as intramural or sumucosal mass rarely
larger then 3 cm. in diameter.
• Tumor in the Stomach & ileum are frequently
multicentric, remainder tend to be solitary.
• Tumor is a yellow-tan appearance on transection &
firm because of desmoplasia.
 Carcinoids
• Rectal & appendiceal carcinoids almost never
metastasize.
• Histologically ,the neoplastic cells may form island,
trabeculae ,glands or undifferentiated sheets.
• Tumor cells are uniform, having a scant,pink
granular cytoplasm & round- to –oval stippled
nucleus.
• Specific hormonal peptides may be identified by
immunocytochemical techniques.
 Carcinoids

• A part of the small

intestine with a
round mass in it –
this is the carcinoid
tumor
 Carcinoid tumour

• The tumor cells

show
monotonous
morphology with
a delicate
fibrovascular
stroma.
Carcinoid tumour

At high magnification, the

nests of carcinoid tumor
have a typical endocrine
appearance with small
round cells having small
round nuclei and pink to
pale blue cytoplasm
 Carcinoid tumour
Clinical features:
Carcinoids tumors are characterized by production
of serotonin (5-hydroxytryptamine; 5-HT)
• The carcinoid syndrome occurs in approximately 10% of
carcinoid tumors and becomes manifest when
vasoactive substances from the tumors enter the
systemic circulation escaping hepatic degradation.
• Carcinoid syndrome will only occur once it
metastasized to the liver
 Carcinoid tumour
• The most important clinical finding is flushing of the skin,
usually of the head and the upper part of thorax.
•  Secretory diarrhea and abdominal cramps are also
characteristic features of the syndrome. When the diarrhea is
intensive it may lead to electrolyte disturbance and
dehydration.
• Other associated symptoms are nausea, and vomiting. 
• Bronchoconstriction affects a smaller number of patients.
 Carcinoid tumour
• About 50% of patients have cardiac abonormalities,
caused by serotonin-induced fibrosis of
the tricuspid and pulmonary valves
• "TIPS" is an acronym
for Tricuspid Insufficiency, Pulmonary Stenosis
• Diagnosis-measuring the 24 hour urine levels of 5-
HIAA (5-hydroxyindoleacetic acid), a breakdown
product of serotonin.
• Patients with carcinoid syndrome usually excrete
>25 mg of 5-HIAA per day
 Carcinoid tumour
Treatment
• For symptomatic relief of carcinoid sydrome:
octreotide (a somatostatin analogue that neutralizes
serotonin and decreases urinary 5-HIAA)

•  An antihistamine drugs

• Surgical resection of tumor and chemotherapy (5-FU

and doxorubicin)
 Malabsorption syndrome
• Malabsorption is the failure of the body to properly
absorb vitamins, minerals, and other nutrients from
food. Even though his or her diet is adequate, an
individual with malabsorption develops various
nutritional deficiencies.
• Most common presentation are chronic diarrhea &
steatorrhea(excessive fat content of the feces).
• Most common malabsorptions syndrome encounter
in USA are pancreatic insufficiency, celic disease, &
Crohn disease
 Malabsorption syndrome
• Malabsorption is the result of disturbance of at least one of
normal digestive functions-
• 1) Intraluminal digestion: In which proteins,carbohydrates &
fat are enzymatically broken down.
• 2) Mucosal absorption: In which water,electrolytes &
nutrients are absorbed & transport into the cell.
• 3) Nutrient delivery: Which involving the delivery of nutrients
from the intestinal cells into the lymphatics.
 Malabsorption syndrome
• 1) Defect of intraluminal digestion-
• Pancreatic insufficiencies:
– cystic fibrosis
– chronic pancreatitis
– Zollinger-Ellison syndrome
– terminal ileal disease
– obstructive jaundice
– bacterial overgrowth
 Intraluminal digestion-
Clinical features-
• Osmotic diarrhea & steatorrhea from
undigested nutrients.
• Most common cause is pancreatic
insufficiency associated with chronic
alcoholism , & Crohn disease.
• Other causes bacterial overgrowth, extensive
ileal resection.
 Defect of mucosal absorption
• 2)Defect of mucosal absorption:
A)Defective terminal digestion
Disaccharidese deficiency(Lactose intolerance)
Abetalipoproteinemia
B) Reduced surface area
Coeliac disease
Crohn disease.
C)Infection- Bacterial & parasitic infection
Tropical sprue
Whipple disease
 Lactose intolerance
• 1) Lactose intolerance is the inability to digest lactose, a sugar
found in milk and milk product
• Lactose intolerance is caused by a deficiency of the enzyme
lactase, which is produced by the cells lining the small
intestine.
• Lactase breaks down lactose into two simpler forms of sugar
called glucose and galactose, which are then absorbed into
the bloodstream.
 Lactose intolerance
• Primary lactase deficiency develops over time and begins
after about age 2 when the body begins to produce less
lactase
• Most children who have lactase deficiency do not experience
symptoms of lactose intolerance until late adolescence or
adulthood
• Secondary lactase deficiency results from injury to the small
intestine that occurs with severe diarrheal illness, celiac
disease, Crohn’s disease, or chemotherapy.
• This type of lactase deficiency can occur at any age but is
more common in infancy
 Lactose intolerance
• Sequence of events
• lactose present in ingested dairy products remains uncleaved
and passes intact into the colon.
• The  enteric bacteria quickly switch over to lactose
metabolism, and the resulting in-vivo fermentation produces
copious amounts of gas (a mixture of hydrogen, carbon
dioxide, and methane).
• Diagnosis is made by measurement of breath hydrogen level.
 Lactose intolerance
• People with lactose intolerance may feel uncomfortable 30
minutes to 2 hours after consuming milk and milk products.
Symptoms range from mild to severe.
Common symptoms include
• abdominal pain
• abdominal bloating
• gas
• diarrhea
• nausea
 Apolipoprotein -B
• Apolipoproteins are carrier proteins that combine
with lipids to form lipoprotein particle
• It is incorporated into intestinally synthesized
cholymicrons and transports dietary triglycerides and
cholesterol
• IT is required for assembly of dietary lipids into
chylomicrons, which are then secreted into intestinal
lymphatic.
 Deficiency of apolipoprotein
• 2) Deficiency of apolipoprotein -B
• Make the mucosal epithelial cell unable to export
lipid.
• Mucosal cells are normal except contain vacuolated
lipid inclusions.
• RBC- acanthocytosis
• Deficiency causes , diarrhea, steatorrhea & failure to
thrive.
Acanthocytes

Red cells with multiple thorn-

like spicules -Found in
association with
hereditary abetalipoprotenemia
 but also seen in severe liver
disease, hepatorenal failure,
anorexia nervosa and in
chronic starvation. -A small
number of acanthocytes may
be found in forms of hemolytic
anemia (especially
post splenectomy)
 Defect of mucosal absorption
B) Reduced surface area
Celiac disease
Crohn disease.
 Celiac disease
• Celiac disease, also known as gluten-sensitive
enteropathy, is the prototype of a noninfectious
cause of malabsorption resulting from a reduction in
small intestinal absorptive surface area.
• Celiac disease is believed to be quite common,
affecting 1 in 300 persons both in Europe and in the
United States, and many patients have subclinical
disease.
• Symptoms include chronic diarrhoea, failure to
thrive (in children), and fatigue, but these may be
absent.
 Celiac disease 
• Celiac disease is an autoimmune disorder of the small
intestine that occurs in genetically predisposed people of all
ages from middle infancy onward.
• Celiac disease is caused by a reaction to gliadin,
(gluten protein) found in wheat, and similar proteins found in
the other crops such as barley and rye.
• Upon exposure to gliadin, the enzyme,  tissue
transglutaminase modifies the protein, and the immune
system cross-reacts with the small-bowel tissue, causing
an inflammatory reaction.
• That leads intestinal villous atrophy. This interferes with the
absorption of nutrients.
• The only known effective treatment is a lifelong gluten-free
diet.
 Celiac disease 
• Biopsy of small
bowel showing
coeliac disease
manifested by
blunting of villi, crypt
hyperplasia,
and lymphocyte 
infiltration
 Celiac disease before Therapy

• Note the total absence of villi.

• Increased inflammatory cells in the surface epithelium.
127
12 Months After GFD
(Normal Again)

128
 Whipple disease
C)Infection- Bacterial
Tropical sprue
Whipple disease
Tropical sprue and Whipple disease are two
disorders that exemplify malabsorption
syndromes arising from intestinal infection.
 Whipple's disease 
• Whipple's disease is a rare, systemic infectious disease
caused by the bacterium Tropheryma whipplei
• Commonly considered a gastrointestinal disorder, Whipple's
disease primarily causes malabsorption but may affect any
part of the body including the heart, lungs, brain, joints, and
eyes.
•  Weight loss, diarrhea, joint pain, and arthritis are common
presenting symptom.
• Approximately 15% of patients do not have these classic signs
and symptoms.
• More common in men, with 87% of patients being male.
 Whipple's disease
• Not much is known about the bacterium. Although it seems
readily present in the environment, scientists don't really
know where it comes from or how it's transmitted to
humans. 
• Not everyone who carries the bacterium develops the
disease.
• Some researchers believe that people with the disease may
have a genetic defect in their immune system response that
makes them more susceptible to becoming ill when exposed
to the bacterium
 Whipple's disease 
• The hallmark is a dense mucosal infiltration by
macrophages with foamy cytoplasm.
• These macrophages have several large lysosomes
which store numerous intact or degraded bacteria.
• Due to the glycoprotein content of the whipple-
bacterial cell wall, lysosomes filled with bacteria
appear as PAS-positive granular particles by means
of light microscopy
 Whipple's disease 
Clinical features:
• Malabsorption
• Intestinal lipodystrophy (accumulation of fatty
deposits in lymph nodes of the intestine)
• Lymphadenopathy
• Abdominal pain
• Diarrhoea
• Fever
 Whipple's disease
• Clinical features(Continue)
• Approximately 90% of patients with Whipple disease
present with weight loss, and 70% of patients with
Whipple disease complain of either diarrhea or
arthralgia.
• Arthralgias or a migratory, non-
deforming Arthritis occurs in 80%.
 Whipple's disease 
• Diagnosis is made by intestinal biopsy, which reveals presence
of the organism as PAS positive  macrophage inclusions.
•  Immunohistochemical staining for antibodies against T.
whipplei has been used to detect the organism in a variety of
tissues
• Confirmatory PCR-based assay is also available.
(The polymerase chain reaction (PCR) is
a technique  to amplify a single or few copies of a piece
of DNA -generating thousands to millions of copies of a
particular DNA sequence)
 Whipple's disease 

Light microscopy of small
intestine;
Whipples Disease: an
infiltrate of
foamy macrophages is
present in the lamina propria
 Whipple's disease 

Picture: intestinal
biopsy and PAS stain.
A.    PAS (periodic
acid Schiff):
glycoprotein in the cell
wall of Tropheryma
whippelii---  magenta
color.
 Whipple's disease
• Treatment is
with penicillin, ampicillin, tetracycline or co-
trimoxazole for one to two years.
•  Any treatment lasting less than a year has an
approximate relapse rate of 40%.
 Tropical sprue
• Tropical sprue is a malabsorption disease commonly
found in the tropical regions, marked with abnormal
flattening of the villi and inflammation of the lining of
the small intestine.
• Tropical sprue is largely limited to within about 30
degrees north and south of the equator.
• Therefore, if one resides outside of that geographical
region, recent travel to the region is a key factor in
diagnosing this disease
 Tropical sprue
• Tropical sprue occurs chiefly in the Caribbean,
southern India, and Southeast Asia.
• Both natives and visitors may be affected, but
children are rarely affected.
• The cause of tropical sprue is not known. It has been
suggested that it is caused by bacterial, viral,
amoebal, or parasitic infection.
• Folic acid deficiency and rancid fat have also been
suggested as possible causes
 Tropical sprue
• Diagnosis of tropical sprue can be complicated
because many diseases have similar symptoms. The
following investigation results are suggestive:
• Abnormal flattening of villi and inflammation of the
lining of the small intestine, observed during
an endoscopic procedure.
• Presence of inflammatory cells in the biopsy of small
intestine tissue.
• Excess fat in the feces (steatorrhoea).
• Thickened small bowel folds seen on barium swallow
 Tropical sprue
• The illness usually starts with an attack of acute diarrhoea,
fever and malaise following which, after a variable period, the
patient settles into the chronic phase of diarrhoea,
steatorrhoea, weight loss, anorexia, malaise and nutritional
deficiencies. The symptoms of tropical sprue are:
• Diarrhea
• Steatorrhea or foul-smelling feces
• Indigestion
• Cramps
• Weight loss and malnutrition
• Fatigue
 Tropical sprue
Treatment
• Once diagnosed, tropical sprue can be treated by a course of
the antibiotic tetracycline(Doxycycline) or
Sulfamethoxazole/Trimethoprim(Co-trimoxazole) and
vitamins B12 and folic acid for at least 6 months.

• Preventive measures include drinking only bottled water,

washing food, avoiding fruits washed with tap water (or
consuming only peeled fruits, such as bananas and oranges)
 Malabsorption
• 3) Defective Nutrient delivery-
• Defect involving the delivery of nutrients from
the intestinal cells into the lymphatics.
• Disturbance may be caused by tuberculosis or
retroperitoneal fibrosis.
 Malabsorption
General Clinical features of malabsorption-
• Syndromes resemble each other like –The passage of
abnormally
bulky ,frothy, greasy, yellow or gray stools.
- Weight loss, anorexia & muscle wasting.
- Hematopoietic system: anemia from iron & vitamin
deficiency.
- Musculoskeletal system: Osteopenia & tetany from
defective calcium,vitamin D & protein absorption.
 Malabsorption
• Endocrine system: Amenorrhea,impotence &
infertility.
• Skin: Purpura & petechiae from vitamin K
deficiency.
• Nervous system : Peripheral neuropathy from
vitamin A & B12 deficiencies.
 Enterocolotis (Diarrheal diseases)
Define as a increase in stool mass, stool frequency or stool
fluidity.
• Law- volume ,painful, bloody diarrhea is known as dysentery.
• Major types-
• 1) Secretary diarrhea
• 2) Osmotic diarrhea
• 3) Exudative diarrhea
• 4)Malabsorption diarrhea
• 5) Derange motility diarrhea
 Enterocolotis
• 1) Secretory diarrhea-
• Stool consist of net intestinal fluid secretion, that isotonic
with plasma & persist during fasting.
Causes-
• Viral infection-Rota virus,norwalk virus
• Bacteria –enterotixin mediated- V. cholera,E.coli,Bacillus
cereus.
• Neoplasm- tumor elaboration of serotonin.
 Enterocolotis
• 2)Osmotic diarrhea-
• Excessive osmatic forces exerted by luminal solutes.
• Abate with fasting
Causes-
• Lactulose therapy for hepatic encephalopathy Or
constipation
• Antacids like Mgso4
 Enterocolotis
• 3) Exudative diarrehea-
• Purulent,bloody stool, persist on fasting.
Causes-Infection with
• Shigella
• Salmonella.
• Campylobactor
• Entamoeba histolytica.
 Enterocolotis
• 4) Malabsorption diarrhea-
• Bulky stool, excess fat & increase osmolarity
resulting from unabsorbed nutrients.
 Enterocolotis
• 5) Deranged motility diarrhea-In order for nutrients and
water to be efficiently absorbed, the intestinal contents must
be adequately exposed to the mucosal epithelium and
retained long enough to allow absorption. Disorders in
motility than accelerate transit time could decrease
absorption, resulting in diarrhea even if the absorptive
process per se was proceeding properly
- Decreased intestinal retention time
• Surgical resection of gut length
• Irritable bowel syndrome
• Hyperthyroidism
 Infectious entrocolitis
• Intestinal diseases of microbial origin are marked by-
• Diarrhea
• Some times by ulceroinflammatory changes.
• 3 million deaths occur annually/world wide.
• 500 infants & young children die in USA/annually.
• Most common organisms are-
rotavirus ,calcivirus & enterotoxigenic E.coli
In 40% to 50% of cases, the specific agent cannot be
isolated.
 Infectious entrocolitis
Viral Gastroenteritis-
• Superficial epithelial cells infected &
destroyed by viruses.
• Repopulated enterocytes & crypts cell secrete
water & electrolytes.
• Incompletely absorbed nutrient cause osmotic
diarrhea.
 Infectious entrocolitis
• 1) Rotavirus are accounting for approximately 60%
of childhood diarrhea
• Age – 6 to 24 months.
• Spread is by fecal-oral contamination.
• Disease last for 3 to 5 days.
• 2) Calcivirus (Norwalk virus)- responsible for most
cases of food born epidemic gastroenteritis in older
children & adults.
• Other viruses are adenovirus-AD-40 & AD-41
 Infectious entrocolitis
Bacterial enterocolitis-
• Mechanisms-
• 1)To produce disease ,organism must adhere to
mucosa. Adherence is often mediated by plasmid
coded adhesin-protein expressed on the surface of
the organism.
2) Toxin present in contaminated food e.g. Staph.
auras, Vibrio & Clostridium perfringens.
 Infectious entrocolitis
• 3) Infection by toxigenic organism- Enterotoxigenic organism
produce polypeptides that activate secretion without
inducing cell damage
• Organism proliferate within gut lumen & elaborate an
enterotoxin. e.g. E. coli, V. cholerea, Clostridium perfringen.
• 4) Infection by invasive organism- Organism invade &
destroyed epithelial cells e.g. salmonells , shigella,
M. tuberculosis.
 Infectious entrocolitis
Morphology:
• 1) E.coli- enterotoxigenic stain (ETEC) & V.cholerae – mucosa
remain intect
• The shiga- toxin producing strain (STEC) –Severe disease in
the right colon with hemorrhage & ulceration.
• 2) Shigella produces acute mucosal inflammation & erosion
• 3) C.pefringens- Features are similar to V.cholerae with some
epithelial damage.Some strain produce severe necrotizing
enterocolitis.
 Infectious entrocolitis
Protozoal infection:
• 1) E. histolytica- Create flash like ulcer in the colon with very
little inflammatory infiltration.
• Parasites may penetrate portal vessels & produce multiple
liver abscess.
• 2) G.lambilia- They attach with mucosa of small intestine but
do not invade.
• Intestine shows blunting of the villi with mixed inflammatory
infiltrate in the lumina propria
• Malabsorptive diarrhea is a clinical presentation.
 Infectious entrocolitis
Clinical presentation of infectious enterocolitis-
• Preformed bacterial toxins –symptoms developed within a
matter of hours.
• Bacteria producing secretory enterotoxin cause watery
diarrhea & dehydration.
• Those producing cytotoxin cause-dysentry.
• Yersinia & mycobacterium infection present as subacute
diarrheal illness mimicking Crohn disease.
• In general, bacterial enterocolitis is a more severe illness than
viral diseases.
 Protozoal causes for
diarrhea
• Giardia lamblia
– A cause of Traveler’s
diarrhea
– Caused by ingestion of
cysts in fecally
contaminated food or
water streams
– Malabsorption syndrome;
diarrhea, abdominal pain
Diagnosis: Cysts and
trophozoites in feces
• Giardiais affects small intestine
161
 Amoebiasis
• Produces a range of infection from
asymptomatic-acute amebic
dysentery-chronic intestinal
infection with granuloma formation;
Most patients present with diarrhea
with mucus and blood and colicky
bowel movements
• “Flask-shaped ulcer” in cecum or
ascending colon (narrow neck and a
broad base)
• Biopsy- Erythrophagocytosis by
trophozoite is diagnostic
• Erythrophagocytosis
• cysts or trophozoites in stool
of a trophozoite
• See a single nucleus and it takes up
RBC’s.
162
 Entamoeba
histolytica trophozoit

Entamoeba
histolytica mature cyst
Amoebic ulcer colon
Narrow neck
and broad
base

164