DISEAESES OF BOWEL

Diseases of bowel
Malabsorption syndrome.
Inflammatory bowel diseases.
Malabsorption Syndromes
Characterized by defective absorption of fats, fat-soluble and other
vitamins, proteins, carbohydrates, electrolytes and minerals, and
water.
Clinical Features:
1. steatorrhea (excessive fat content of the feces).The passage of
abnormally bulky, frothy, greasy, yellow or gray stools.
2. weight loss.
3. Anorexia.
4. Abdominal distention.
5. Muscle wasting.
Celiac disease
An auto-immune disorder.
Strongly associated with HLADQ2, HLADQ8, HLA-B8 & prior
infection with adenovirus type 12.
Variable presentation from minor nutritional deficiencies to
more severe steatorrhea, malnutrition, and weight loss.
Increased incidence of malignancy (small intestinal T-cell
lymphoma and adenocarcinoma)
Celiac disease
Pathology & Pathogenesis:
Intestinal epithelial injury caused by dietary wheat gluten (and
particularly, its alcohol-soluble fraction, gliadin).
Circulating antigliadin, antiendomysial, and tissue transglutaminase
antibodies + in > 90% of the untreated patients.
Celiac disease
Macroscopic
Most severe in the proximal jejunum and duodenum
Ileum is usually spared or minimally affected
Loss of valvulae resulting in a smooth, tubular appearance of
the small intestine
 Celiac disease
Microscopic:
Increased intraepithelial T
lymphocytes
Villous blunting from mild to totally
flat mucosa
Increased crypt epithelial mitosis
Dense lymphoplasmacytic infiltrate
in lamina properia.
Celiac disease
Celiac disease
Diagnosis depends on clinicopathological findings, including
typical symptoms, positive celiac disease autoantibodies and
supportive histopathology.
Whipple Disease
Rare.
A systemic infectious disease often diagnosed through duodenal
biopsies
Caused by Tropheryma whippelii.

C.F:
Fever, weight loss, polyarthralgias and diarrhea.
Whipple Disease
Macroscopic:
Primarily involves the jejunum
Microscopic
Marked villous atrophy.
Foamy macrophages in lamina properia.
Rod-like intracellular organisms strongly + on periodic acid-Schiff
(PAS) with diastase stain.
Polymerase chain reaction (PCR) specifically identifies the bacterial
genome
Whipple Disease
Inflammatory bowel disease (IBD)
Is an immune-mediated chronic intestinal inflammatory conditions.
It results from inappropriate mucosal immune activation in
genetically susceptible persons.
Major types of IBD:
1) Ulcerative colitis (UC) and
2) Crohn disease (CD ).
Etiology and Pathogenesis
IBD are an idiopathic disorders. The exact trigger for inflammatory
bowel disease is not known.
Present evidences suggest that IBD represents the outcome of three
main interactive factors:
genetic, environmental and host factors.
Hypothesis for Pathogenesis of IBD
IBD results from the combined effects of alterations in host interactions
with intestinal microbiota, intestinal epithelial dysfunction, abnormal
mucosal immune responses, and altered composition of the gut
microbiome.
 CROHN DISEASE
A chronic granulomatous disease which can affect any part of the
gut from the esophagus to the large intestine but the most
commonly affected part is small intestine particularly the ileum.

It is associated with HLADR1/ DQw5 and NOD2 genes and an

abnormal T-cell response particularly, CD4+ T cells (TH1 cells Q).
Morphological Features: Gross
The earliest morphological changes called aphthous ulcer.
The involved bowel segment shows full thickness
involvement.
This causes thickened wall and stricture or
weakness in the wall leading to fissure and fistula (Perianal
fistula is the most common fistula seen).
Intestinal stricture
Morphological Features: Gross
There is patchy involvement of the intestine which is known

The intervening area between two affected portions is

normal.
So, the mucosa appears to be irregular which is known as
Morphological features: microscopy
There is trans-mural inflammation.
Focally intense cryptitis, crypt abscess
There is a presence of non-caseating granulomas.
Clinical features
There are intermittent attacks of abdominal pain, blood in stools, and
fever.
there may be steatorrhea and megaloblastic anemia because there is
impairment in the absorption of bile acids and vitamin B12
respectively from the ileum).
Extraintestinal manifestations affecting the skin, eyes, and joints
Complications of disease
I. Acute complications Perforation, haemorrhage,
II. Malabsorption syndrome: Often iatrogenic ( short bowel
syndrome )
III. Fistula formation.
IV. Anal lesions Skin tags, fissures, fistulae
V. Malignancy Increased risk adenocarcinoma
VI. Systemic amyloidosis
Ulcerative colitis
Chronic relapsing inflammatory disorder, but it may have an acute
fulminating presentation.
Associated with the passage of blood, mucus and pus.
It usually start in distal colon, involving the rectum (ulcerative proctitis)
and extend proximally in variable length.
it may affect the whole length of the large intestine (pancolitis) and
involvement of the terminal ileum in a so-
the appendix are occasionally seen.
Ulcerative colitis
Macroscopic
Mucosa appears hyperemic and granular, with multiple ulcers
microscopic
The inflammation is diffuse and limited to the mucosa.
cryptitis and crypt abscesses.
The presence of numerous plasma cells at the base of the
mucosa (basal plasmacytosis) is a key finding of ulcerative
colitis.
Crypt atrophy and distortion.
Complications of ulcerative colitis
Blood loss: May be acute (hemorrhage) or chronic, leading to
anaemia
Electrolyte disturbances: Due to severe diarrhoea in acute
phase
Toxic dilatation: May develop insidiously
Colorectal cancer Overall incidence 2%
Complications of ulcerative colitis
Skin involvement: erythema nodosum, pyoderma
gangrenosum
Liver involvement: Fatty change, chronic pericholangitis,
sclerosing cholangitis, cirrhosis, hepatitis
Eye involvement: Iritis, uveitis, episcleritis
Joint involvement: Ankylosing spondylitis, arthritis
 Vs ulcerative colitis
Feature Ulcerative colitis

Distribution Commonly terminal ileum, but may occur anywhere Colon and rectum
from mouth to anus
Skip lesions Common -

Affected bowel Thickened wall and narrowed lumen Mucosal ulceration and
dilated lumen
Extent of inflammation Transmural Mainly mucosal

Granulomas Often present (c. 60%) -

Fissures and Common Rare

fistulae
 Intestinal polyp
A colorectal polyp is a mass that protrudes into the lumen of the gut.
They are heterogeneous with variability in:
Size.
Morphology.
Molecular genetics. &
Cellular origin.
Classification of gastrointestinal polyps

According to macroscopic
appearance
Sessile Polyps no stalk

Pedunculated Polyps have

a stalk
 Classification of intestinal polyp
According to histology:
Non-neoplastic:
1. Inflammatory.
2. Hamartomatous.
3. Hyperplastic.
Neoplastic:
1. Benign epithelial polyps: Adenoma (Tubular, tubulovillous and villous)
2. Benign mesenchymal polyps: lipomas.
3. Malignant epithelial and lymphomatous polyps.
 Neoplastic polyp
Architecture: by microscopy
1. Tubular.
2. Tubulovillous.
3. Villous.
Macroscopy of adenomas
 Familial Adenomatous Polyposis
FAP is an autosomal dominant syndrome characterized by
hundreds of adenomas throughout the colorectum as well as a
numerous extra colonic manifestations.

Minimum of 100 polyps are necessary for a diagnosis of FAP.

Precancerous condition: all untreated FAP patients develop

colorectal adenocarcinoma.
FAP
Genetic features
Caused by germline inactivation mutations of the adenomatous
polyposis coli (APC) gene.
APC is a tumor suppressor gene, that modulate a specific signaling
cascade (WNT signaling) that regulates cell proliferation.
Every cell of FAP patient has one inactive APC allele and
inactivation of second allele initiate the early phase of neoplastic
change.
 Familial polyposis syndromes

Attenuated FAP:

Gardner syndrome: Intestinal polyp + osteomas of mandible, skull,

and long bones, epidermal cysts, desmoid tumors in the abdominal
wall, thyroid tumors, etc.

Turcot syndrome: Colonic adenomas + tumors of the central nervous

system (medulloblastomas).
Hereditary Non-polyposis Colorectal Cancer (HNPCC)
Also known as Lynch Syndrome
Autosomal dominant condition.
Characterized by increased risk of
1. Colorectal cancer;
Often found in the right proximal colon.
It is usually of mucinous type.
2. Extra-colonic cancers: including cancers of the
endometrium, ovary, stomach and urinary bladder.
 Genetics of HNPCC
Caused by germline mutations in DNA mismatch repair (MMR)
genes.

These are tumor suppressor genes encode proteins involved in

repairing small sequence errors that occur during DNA replication.

HNPCC patients inherit one defective copy of an MMR gene, and the
second one is lost later (somatic lesion.)
 Bowel tumors
Most of bowel tumors are adenocarcinomas, and most of them arise
in the colon Colorectal cancer.

Tumors of the small intestine are rare.

Etiology
a. Environmental causes:

Dietary Factors

Low intake of dietary fiber.

High intake of refined carbohydrates and fat.

Diets rich in vegetables and vitamin A is protective.

Deficiencies of vitamins A, C, and E, which act as antioxidants

b. Genetic factors
Adenoma-carcinoma Sequence:
The colonic adenocarcinoma may develop from the pre-
existing adenomas.
Hereditary Non-polyposis Colorectal Cancer (HNPCC).
Pathogenesis
Genetic Pathways:
Two genetic pathways have been described:
A) Classic adenoma-carcinoma sequence.
B) Microsatellite instability pathway.
 macroscopy

Location: Colonic adenocarcinomas can be found in any location of the

colon.

1. Exophytic polypoid mass in the right-side of colon.

2. Annular and constricting tumors in the left-side of colon, apple core .

3. Diffuse/tubular tumors similar to linitis plastica of the stomach.

Macroscopy
Macroscopy
microscopy
Clinical Features
Rectal bleeding.
Fatigability Iron deficiency anemia.
Altered bowel habits
Abdominal pain.
Abdominal mass.
Intestinal obstruction.
Colo-rectal cancer spread

Direct spread.

Lymphatic spread: into the regional lymph nodes.

Blood spread: liver (through portal vein) or lungs and bones.

Transcoelomic spread:
Complications of colo-rectal cancer
local Colitis.
Ulceration: Iron deficiency anemia.
Perforation.
Intestinal obstruction.
Malabsorption.
Metastasis.
 Diagnosis
A. Laboratory diagnosis:
1. Fecal Occult blood.
2. Tumor markers: carcinoembryonic antigen (CEA) and CA 19-9.
3. final diagnosis is by biopsy and histopathology.

B.- Sigmoidoscopy and Colonoscopy direct visualization of cancer and

used to take a biopsy:
Endoscopy
Nodular elevated
lesion
adenocarcinoma.
 Diagnosis
C. Radiology: localization and staging.
1. Barium enema:
2. Ultrasonography: liver metastases
3. Spiral CT:
 Radiology: barium enama

Filling defect: core apple

appearance.
 Staging and Prognosis
The most important prognostic factors are: depth of invasion
and the presence or absence of lymph node metastases
i.e.:
Staging:
Dukes staging.
TNM (tumor-nodes-metastasis) classification and staging
system from the American Joint Committee on Cancer.
TNM STAGING
 CARCINOID TUMOR
Carcinoid tumor arises from the endocrine cells called as
argentaffin tissue.
The clinical features are due to release of peptide and non-
peptide
hormones from these cells.
 CARCINOID TUMOR
The gastrointestinal carcinoid tumors can be of the following
types:
1. Foregut carcinoid tumors: Arise from the esophagus,
stomach and the duodenum these are usually have indolent
course.
2. Midgut carcinoid tumors: Arise from the jejunum and ileum;
these are aggressive and metastasize frequently. liver
3. Hindgut carcinoid tumors: Arise from the appendix, colon
and rectum; usually have indolent course.
Morphology
Macroscopy:
On section, the tumors show a characteristic solid, yellow
appearance
Microscopy:
They stain positively with chromogranin A, neuron-specific
enolase and synaptophysin on immunocytochemistry.
 Carcinoid tumors
Carcinoid tumors may be associated with increase level of:
5-HT and its degradation product, 5-Hydroxy-indole acetic acid
(5-HIAA) Histamine, Kallikrein and Bradykinin
5-HT is:
Potent vasodilator .
smooth muscle stimulant.
Midgut carcinoids produce large quantities of 5-HT and 5-
HIAA High frequency of carcinoid syndrome in them.
 Carcinoid syndrome
Present in 1% patients of carcinoid tumor and it is due to
excessive release of serotonin (5-HT).
It is strongly associated with metastatic disease.
Component of carcinoid syndrome:
1. Intermittent attacks of flushing of the skin of face.
2. Episodes of watery diarrhea.
3. Abdominal pain.
4. Attacks of dyspnoea bronchospasm
Carcinoid syndrome
2. Cardiac lesions:
Present in 50% of the patients with the carcinoid syndrome.
Located mainly in the right ventricle, tricuspid and pulmonic valves,
or major blood vessels.
The commonest cardiac manifestation is the tricuspid regurgitation
followed by pulmonary regurgitation.
 Anal tumors
Epithelial tumors of the anal canal are uncommon and may
be combination of several histological types.
Benign tumors of the anal canal, includes:
Multiple viral warts called condyloma acuminate and it is
associated with viral infection with human papilloma virus.
 Malignant tumors of anal canal
It includes the following:
1. Squamous cell carcinoma.
2. Basaloid carcinoma
3. Adenocarcinoma (rectal, of anal glands)
4. Undifferentiated carcinoma
5. Malignant melanoma.
These tumors resemble in morphology with similar lesion elsewhere in
the body.
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