CONGENITAL ANOMALIES:

● Heterotopic pancreas
● Heterotopic gastric mucosa: present as discrete small nodules or sessile polyps in the
duodenum.
● Intestinal duplication: More commonly occur in the ileum.
● Intestinal atresia: Can involve any portion of the small bowel. Obliteration of bowel lumen
and its replacement by a fibrous cord.

MECKEL’S DIVERTICULUM
●
● 2% of the population.
● 80 cm proximal to ileocecal valve.
● Mucosa is predominantly of small intestinal type.
● However, gastric, duodenal and colonic mucosa may be found usually ​near the tip​.
● Perforation, hemorrhage, ulceration, intussusceptions, vesico-diverticular fistula,
intestinal obstruction may be present.

HIRSCHSPRUNG’S DISEASE
When involving the whole colon may extend to the small intestine.

Absence of ganglion cells in both plexuses of a segment of bowel [ a distal intestinal segment
that lacks both the Meissner submucosal and the Auerbach myenteric plexus (“aganglionosis”) ]

This is associated with hypertrophied, disorganized nerve fibers in the aganglionic segment.

Fibro-muscular dysplasia in the arteries located in the transitional zone between aganglionic
and dilated segment.

Hyperplasia of the lympho-glandular complex.

Intestinal obstruction of GIT can occur at any level but the small intestine in more frequently
involved.Hernias, intestinal adhesions, intussusceptions and volvulus accounts for 80% of
cases.Tumors, helminths and infarction 10% of cases.

Definitions:

❖ Intussusception​: When a segment of intestine telescope into the immediately distal

segment.
 ❖ Volvulus​: Complete twisting of a loop of bowel about its mesenteric base of attachment.
❖ Hernias​: A defect in the wall of the peritoneal cavity that permit protrusion of a serosa
lined pouch of peritoneum called hernia sac.

MALABSORPTION
▪ Malabsorption: is defective absorption of nutrients from GIT and
▪ presents most commonly as ​chronic diarrhea​.
▪ characterized by;
-Defective absorption of fats
-Fat soluble vitamins
-proteins
-Carbohydrate
-Electrolytes
-Minerals and water

Phases of absorption
1. Intraluminal digestion
2. Terminal digestion
3. Intraepithelial transport
4. Lymphatic transport of absorbed lipids.

Malabsorption results from disturbance in any of these phases.

DIARRHOEA​ ​is defined as

o Increase in stool mass
o Frequency
o Fluidity
o Typically greater than 200gm per day
o Diarrhea lasting for more than 4 weeks is called ​chronic diarrhea​.
o Painful, bloody, small volume diarrhea is called ​dysentery.

Diarrhea can be classified into 4 major categories​:

1) Secretory diarrhea​: is characterized by isotonic stool and persists during fasting.
2) Osmotic diarrhea​: Excessive osmotic force exerted by unabsorbed luminal solutes, eg-
lactase deficiency.
3) Malabsorption diarrhea​: failure of nutrient absorption and is associated with steatorrhea
and is relieved by fasting.
4) Exudative diarrhea​: is due to inflammatory disease and is characterized by purulent
bloody stool.
 Causes​:
I. Secretory diarrhea
Viral damage​ to mucosal epithelium
1.Rota virus
2.Calici virus
3.Enteric adenovirus
4.Astrovirus

II. Entero-toxin mediated

1.Vibrio cholerae
2.E.coli
3.Bacillus cereus

III. Osmotic Diarrhea

1.Lactase deficiency
2.Lactulose therapy
3.Primary bile acid malabsorption
4.Antacids (MgSO4)

IV. Exudative Disease

1.Shigella
2.Salmonella
3.Campylobacter
4.Entamoeba histolytica

V. Diarrhea due to deranged motility

1.Surgical reduction of gut
2.Irritable bowel syndrome
3.Diabetic Nephropathy
4.Carcinoid syndrome

VI. Malabsorptive Diarrhea

1.Defective intraluminal digestion
2.Primarily mucosal cell abnormality
3.Lymphatic obstruction
4.Giardia lamblia
List of disease-causing malabsorption and diarrhea:
i. Cystic fibrosis
ii. Celiac disease
iii. Tropical sprue
iv. Primary bile acid malabsorption
v. Disaccharidase deficiency
vi. Abeta-lipo-proteinemia
vii. Inflammatory bowel disease
viii. Autoimmune enteropathy
ix. Parasitic
x. Whipple's disease
xi. Carcinoid syndrome

CELIAC DISEASE
● It is an immune mediated enteropathy triggered by ​ingestion of gluten​ containing cereals
such as wheat, rye or barley in genetically predisposed individuals.
● Gluten is a major storage proteins of wheat and similar grains, ​the alcohol soluble
fraction of gluten is gliadin.

​PATHOGENESIS
● The intestinal epithelial cells express IL-15 to gliadin peptides in predisposed
individuals
● Activate CD8 T-lymphocyte
● The activated lymphocyte become cytotoxic and kill enterocyte
● There is loss of mucosal brush border surface that accounts for absorption.
● A screening serologic test and detection of disease associated antibody is available.

MORPHOLOGY:

The second portion of duodenum and proximal jejunum are affected-

i. Increased number of ​intraepithelial lymphocytes

ii. Cryptic show hyperplasia​ and crypt epithelium show increased mitotic activity
iii. Villous atrophy
iv. Increased number of plasma cells in the upper portion of lamina propria ​(mast cells,
eosinophil, and lymphocytes are also present.)

▪ Biopsy of ​small bowel​ showing coeliac disease manifested by

▪ Blunting of ​villi,
▪ Crypt hyperplasia and
▪ Lymphocyte​ infiltration of crypts
TROPICAL SPRUE
✔ A malabsorption syndrome
✔ That occur almost exclusively in people living in the tropics or
✔ In peoples visiting tropics
✔ No definite organisms have been identified but overgrowth of bacteria has been
documented.
✔ Cyclospora or enterotoxigenic E.coli bacteria has been suggested as an etiologic factor.
✔ Histologic changes are similar to celiac disease
✔ But total villous atrophy in uncommon

IRRITABLE BOWEL SYNDROME

Characterized by
1.Chronic ,relapsing abdominal pain
2.Bloating
3.Changes in the bowel habit
Despite real symptoms, the gross and microscopic evaluation is normal.
Pathogenesis of IBS is poorly defined.
There is clearly an interplay between
1.Psycologic stress
2.Diet and
3.Abnormal GI motility
There may be impairment of signaling in the brain gut axis.

DIAGNOSIS

IBS is presently diagnosed using 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. Other causes, such as enteric
infection or inflammatory bowel disease, must be excluded.

INFLAMMATORY BOWEL DISEASE

I​t is a chronic condition resulting from ​inappropriate mucosal immune activation
Two disorders that comprise IBD
Crohn’s disease
Ulcerative colitis

Epidemiology of inflammatory bowel disease:

 1) Both ulcerative colitis and Crohn’s disease are common in females and are frequently
present in early in early teens or early 20’s.
2) Geographical distribution most common in North America and Northern Europe.
3) The incidence worldwide is becoming common in Asia and other regions.

Ulcerative colitis is limited to the colon and rectum and extends only into the mucosa and
submucosa.

In contrast, Crohn disease, which has also been referred to as regional enteritis (because of
frequent ileal involvement) may involve any area of the GI tract and is typically transmural.

Pathogenesis for IBD

Most investigators believe that two diseases result from combinations of defects.

a) In host interaction with intestinal microbiota,

b) Intestinal epithelial dysfunction and
c) Aberrant mucosal immune response.

o Genetic predisposition
o NOD2 (nucleotide oligomerization binding domain-2) gene as a susceptibility to Crohn’s
disease.
o NOD2 gene products bind with intracellular peptidoglycans and activated NF-kB.
o The disease associated NOD2 variants less effective in recognizing and combating
luminal microbes.

CROHN’S DISEASE
o Crohn’s disease​: which has also been referred as a regional enteritis (because of
frequent ileal involvement),
may involve any area of GIT and is typically transmural involvement.

ETIOLOGY

1. Present at any age (peak in teens and early 20s)

2. Females predominate
3. Whites are affected more often than blacks
4. Regional involvement (skip lesions)
5. Sharply demarcated transmural inflammation
6. Non-caseating granulomas in 35% cases
 7. Systemic manifestation.

LOCATIONS

Crohn disease may occur in any area of the GI tract, but the most common sites involved at
presentation are the terminal ileum, ileocecal valve, and cecum.

o Involves small intestine alone in 40%

o Small intestine and colon 30%
o Colon alone 30%

GROSS FEATURES
1. The bowel wall is thick with edema, inflammation, fibrosis, hypertrophy of muscularis
mucosa leading to stricture (lumen is narrow)
2. Punched out mucosal ulcer and linear ulcers
3. Granular inflamed serosa and thick mesentery.
4. Mesenteric fat frequently extends around the serosal surface (creeping fat)
5. The patchy distribution of Crohn disease, results in a coarsely textured, cobblestone
appearance in which diseased tissue is depressed below the level of normal mucosa

MICROSCOPICALLY
I. Mucosal ulceration & inflammation
II. Intraepithelial neutrophils
III. Crypt abscess
IV. The lamina propria mononuclear infiltrate.
V. Chronic mucosal damage with villous blunting, atrophy, metaplasia and architectural
disarray.
VI. Noncaseating granulomas a hallmark of Crohn disease, are found in approximately 35%
of cases.

CLINICAL FEATURES
1. Intermittent attack of diarrhea,
2. Fever,
3. Abdominal pain,
4. Weight loss,
5. Intervening as asymptomatic periods
 6. What is a skip lesion​:
Skip lesions are multiple, separate, sharply, delineated areas of inflammation with
intervening healthy areas.

ULCERATIVE COLITIS​:
Ulcerative colitis​:
1.is a severe ulcerating inflammatory disease
2.that is limited to colon and rectum and
3.Extends only the mucosa and submucosa.

Is a severe ulcerating inflammatory disease that is limited to colon and rectum and extends only
the mucosa and submucosa.

1) Occurring in young to older adulthood (peak 20-25 years)

2) The lesion extends in a continuous fashion beginning in the rectum.
3) Granulomas are present.

MACROSCOPICALLY

- Mucosa may be reddened, granular or friable with inflammatory pseudopolyps

- Mucosa may show extensive ulcerations or may be atrophic of inflamed

MICROSCOPICALLY

1. Mucosal inflammation similar to crohn’s disease with crypt abscesses,

2. ulceration, chronic mucosal damage,
3. glandular architectural distortion
4. mucosal dysplasia

Differences between Ulcerative colitis and Crohn’s Disease

(Macroscopic)

CROHN’S DISEASE ULCERATIVE COLITIS

Bowel region: ileum & colon Colon only

Distribution of lesion: skip lesion Diffuse lesions

Strictures develops Stricture is rare

Wall appearance: the wall is thick The wall is thin

Rectal bleeding uncommon Rectal bleeding common

MICROSCOPIC

CROHN’S DISEASE ULCERATIVE COLITIS

Inflammation is transmural Inflammation is limited to mucosa

Pseudo-polyps moderate Pseudo-polyps are marked

Ulcers are deep and knife Ulcers are superficial and broad based

Lymphoid reaction is marked Lymphoid reaction is moderate

Fibrosis is marked Fibrosis is mild to none

Serositis is marked Seroisitis is mild to none

Granulomas are found in 35% of cases Granulomas are not formed

Fistula/sinuses may develop No fistulas or sinuses

Colon carcinoma rare Carcinoma 5-10%

CLINICAL DIFFERENCE

CROHN’S DISEASE ULCERATIVE COLITIS

Perianal fistula No perianal fistula

Fat/vitamin malabsorption No malabsorption

Recurrence after surgery Recurrences do not occur

Toxic megacolon may develop Toxic megacolon is not develop

(read tumors of intestine from guide pg 458)

TUMORS OF SMALL INTESTINE

The small intestine represents 75% of the length of GI tract yet contributes 3% to 6% of the
tumors

Malignant to Benign ratio= 1.5 : 1

Benign lesions are

a. leiomyoma
b. lipoma
c. neuroma
d. vascular malformations
e. hamartomatous lesions
f. adenomas

Adenoma frequently occur in the region of ampulla of vater.

# Benign adenoma

1. Tubular adenoma
2. Villous adenoma
3. Tubulo-villous adenoma
4. Serrated adenoma

#Malignant

1. Adenocarcinoma
2. Carcinoid tumors
3. Anal-zone carcinoma

Mesenchymal lesions

1. Gastro-intestinal stromal tumors (benign to malignant)

2. lipoma
3. Neuroma
4. Angioma
● Non-Hodgkin’s lymphoma

ADENOMA
These are benign epithelial neoplasm that forms glandular pattern or the tumors derived from
glands

Types- 1. Tubular 2. Villous

COLITIS
Inflammation of the lining of the colon

Types-

1. Collagenous
2. Lymphocyte
3. Ulcerative
4. Eosinophilic
5. Tuberculous
6. Ischemic
7. Obstructive

INTESTINAL POLYPS

Most polyps begins as small elevations of the mucosa.

Polyp refers to any nodule or mass that project above the level of surrounding mucosa.

Polyps are most common in the colon but they may occur in the esophagus, stomach and in
small intestine.

1. Polyp may be sessile polyps (without stalk) or

2. Pedunculated polyps ( polyps with stalk)

Non-neoplastic polyp

1. Hamartomatous polyp
2. Inflammatory polyp
3. Hyperplastic polyp

Neoplastic polyp

1. Most common neoplastic is adenoma.

Adenoma has potential to progress to cancer

INFLAMMATORY FIBROID POLYP

- centered in the submucosa

- vascular and fibroblastic proliferation
- Inflammatory response usually dominated by eosinophils.

INFLAMMATORY POLYP FORMS PART OF SOLITARY RECTAL ULCER SYNDROME:

● A triad = Rectal bleeding + mucus discharge + an inflammatory lesion in the anterior

rectal wall
 1. Superficial erosions/ulceration
2. Dilated glands/ hyperplasia of the crypts
3. obliteration of lamina propria by fibroblasts, elastin
4. and an inflammatory infiltrate.

HYPERPLASTIC POLYP

- sessile and small size > 5mm

- Elongated glands and intraluminal infoldings, resulting in a saw tooth configuration
- Epithelial cells have inconspicuous basal nucleus
- Basement membrane beneath the surface is thickened

HAMARTOMATOUS POLYP

1. JUVENILE POLYP
- most frequent colonic polyps in children
- less than 3 cm in diameter
- one third of cases occur in adults
- the surface is ulcerated
- contain cystically dilated glands filled with mucus
- Inflamed, edematous stroma composed of lamina propria
2. PEUTZ-JEGHERS POLYP
- Autosomal dominant
- polyps may occur in small intestine, stomach and colon
- polyps are pedunculated
- disorganized glands, lack of atypia
- the stroma contains smooth muscle bundles, connective tissue and lamina
propria

SESSILE SERRATED ADENOMAS

- Overlap with hyperplastic polyps

- common in the right colon
- serrate architecture throughout the full length of glands, including the crypt base
- associated with lateral growth and crypt dilation.

TYPES OF NEOPLASTIC POLYP

Benign tumor

● Adenomatous Polyp
- tubular adenoma
- Villous adenoma
 - Tubulo-villous adenoma

has potential to progress to cancer

● Malignant tumor
- Polypoid carcinoma

TUBULAR ADENOMA

- single or multiple
- pedunculated or sessile
- there is an increase in the number of glands per unit area
- Glands are surrounded by loose stroma and scattered bundles of muscularis mucosa
- the cells are crowded and contain enlarged hyperchromatic nuclei
- mild, moderate or severe atypia

VILLOUS ADENOMA

- Most are large 3-10 cm in diameter, broad or sessile

- it has papillary villous projections
- cytological hall-mark of epithelial dysplasia is nuclear hyperchomasia, elongation and
stratification

TUBULO-VILLOUS ADENOMA

- Usually sessile
- have a mixture of tubular and villous elements

FAMILIAL ADENOMATOUS POLYPOSIS

- autosomal dominant disorder
- patient develops numerous colorectal adenomas
- mutation of adenomatous polyposis coli (APC) gene

GARTNER SYNDROME
- Intestinal polyps + Osteoma of mandible, skull & long bones + Epidermal cysts + thyroid
tumor

TURCOT SYNDROME
 - Intestinal adenomas + CNS tumors

HEREDITARY NON-POLYPOSIS COLORECTAL CANCER (HNPCC)

- In HNPCC colon cancer occur at younger ages
- often located in the right colon
- also known as Lynch syndrome
- caused by inherited mutation in APC gene(70%) or
- Mutation in gene that is responsible for DNA repair (10%)

MALIGNANT TUMORS OF COLON

Epithelial

1. Adenocarcinoma
2. Carcinoid tumors
3. Anal zone carcinoma

Mesenchymal

1. Gastro-intestinal stromal tumors

Lymphoid tumors

1. Lymphoma

COLORECTAL ADENOCARCINOMA
- Adenocarcinoma of colon is the most common malignancy of gastrointestinal tract
- It is a major cause of morbidity and mortality worldwide
- In contrast to the small intestine which accounts for 75% of length of GIT is an
uncommon site for benign and malignant tumors
- Among the malignant small intestinal tumors; adenocarcinoma and
- Carcinoid have roughly equal incidence followed by lymphoma and malignant GISTs

Epidemiology of colo-rectal carcinoma

● Colo-rectal adenocarcinoma represents 15% of all cancer deaths

● Peak incidence is 60-70 years
● <20% cases occur before age 50 years
● Males are more slightly affected than females
● Most prevalent areas are USA, Canada, Australia, New Zealand, Denmark
● The incidence is 3 fold lower in India and South East Asia
● Dietary factors: Low intake of unabsorbed vegetable fiber
● High intake of refined carbohydrates and fat
● Reduced fiber content decreases stool bulk and alter the composition of intestinal
microbiota
 ● Alteration of intestinal mico-biota causes increased synthesis of toxic oxidative by
products of bacterial metabolism
● These free radicals expected to remain in contact with colonic mucosa for longer
periods of time as a result of reduced stool bulk.
● Deficiency of Vitamin A, C and E which act as a free radical scavenger and may
compound damage caused by free radicals
● High fat intake, increases hepatic synthesis of cholesterol and bile acids which
can be converted into carcinogen
● Aspirin and other NSAIDs has protective effects in colorectal carcinoma.
Because of inhibition of cyclo-oxygenase-2 which in highly expressed in colonic
carcinoma

PATHOGENESIS

● There are genetic and epigenetic abnormality

● Two genetic pathway have been described
1. APC/ B-catenin pathway

classic adenoma carcinoma syndrome

2. Microsatellite inhibitory pathway

(associated with defect in DNA mismatch repair)

MORPHOLOGY

- Distribution of adenocarcinoma is approximately equal over the entire length of colon

- caecum and ascending colon 38%, Transverse colon 18% , descending colon 8% ,
sigmoid colon 30%
- 99% of carcinoma occur slightly.

Macroscopically

- The tumors of the proximal colon often grow as polypoid exophytic masses that extend
along one wall of the larger caliber caecum and ascending colon
- Carcinoma of the distal colon tends to be annular lesions that produce napkin ring
constrictions and luminal narrowing
- Sometimes to the point that causes intestinal obstruction but obstruction is uncommon in
proximal colon tumors.
- The margin of napkin ring are classically heaped up & ulcerated

Microscopically

- The tumors are composed of all tall columnar cells; the cells show features of dysplastic
changes forming glands
 - Invasion of these tumors into sub-mucosa and muscle coat elicit a desmoplastic reaction
that responsible for firm consistency.
- Some poorly differentiated tumors form few glands. Some tumors are composed of
signet ring cells.
- Others produce abundant mucin that accumulate within intestinal wall

CLINICAL FEATURE

- Endoscopic examination provides a unique opportunity for cancer perversion’

- Caecal and right sided colon cancers most often called to clinical attention by
appearance of fatigue and weakness due to iron deficiency anemia
- Left sided adenocarcinoma may produce occult bleeding; changes in bowel habit or
cramping left lower quadrant discomfort

METASTASIS

The two most important prognostic factors are depth of invasion and the
presence of lymph node metastases. Invasion into the muscularis propria confers
significantly reduced survival that is decreased further by the presence of lymph node
metastases.

Metastases may involve regional lymph nodes, lungs and bones, but as a result
of portal drainage of the colon, the liver is the most common site of metastatic lesions.
The rectum does not drain via the portal circulation, hence carcinomas of the anal region
that metastasize often circumvent the liver.

MODIFIED ASTLER-COLLER SYSTEM

A Tumor invades submucosa

B1 Tumor invades into, but not through, muscularis propria

B2 Tumor invades through muscularis propria / Penetration into

visceral peritoneum

B3 Invasion into other organs or structures

C1, C2 , C3 Relevant B category with lymph node metastasis

D Distant metastasis

GASTROINTESTINAL LYMPHOMAS
 - About 40% non-hodgkin’s lymphoma occur in extranodal sites. The gut is the most
common site for extranodal NHLs
- They are usually sporadic neoplasm (1-4% of GI malignancy)
- Primary GI- lymphoma exhibit no evidence of liver, spleen or bone marrow involvement
at the time of diagnosis
- Any segment of gut may be affected in secondarily in systemic NHL

CAUSES of GI NHLs

1. Patients with H. pylori chronic gastritis

2. Natives of mediterranean region
3. Patients with congenital immune deficiency
4. Patients with HIV
5. Patients receiving immunosuppressive therapy
6. Young adults with long standing sprue

TYPES OF LYMPHOMA

1. Sporadic lymphoma originates more commonly from B-lymphocytes derived from

mucosa associated lymphoid tissue (MALT)
- arise from stomach, 55%-60%
- small intestine, 20-30%
- colon, 20-25%
2. Other lymphomas are mediterranean lymphoma
3. and Sprue related lymphoma

● A variety of spindle cell lesions from muscle wall of any segment of gut. GIST accounts
for 2% of gut malignancies. It arises from Cajal cell; intercalated with smooth muscle cell
and autonomic neural plexus
● It affects 50-80% years and have equal sex distribution
● The tumor is IHC positive for CD117 and CD34 in (70%-80%) of cases
● C-KIT mutation is seen in 85% of cases

Depending on the cell type

- Spindle cell GIST

- Epithelioid GIST

CLINICAL PICTURE

- vagues upper abdominal pain’

- peptic ulcer
- haemorrhage
- wt. loss
 - intestinal obstruction

Difference between benign, low malignant potential and malignant GIST

GIST BENIGN BORDER-LINE MALIGNANT

Size <5cm 6-10cm >10cm

Mitosis <5/40 HPF No more than 5/40 >5/40 HPF

HPF

Metastasis Absent 30% 60%