GIT REVISION

CONGENITAL AGANGLIONIC MEGACOLON

▪ Hirschsprung disease - congenital disorder –
aganglionosis of a portion of intestinal tract
▪ Intestinal segment lacks both MEISSNER
submucosal and AUERBACH myenteric plexus
▪ Loss of enteric neural coordination –
functional obstruction,
dilatation proximal to affected segment
▪ Clinical - newborn –
failure to pass meconium
Treatment – surgical resection of aganglionic segment
 distal intestinal segment
▪ Rectum and sigmoid colon usually involved
▪ Proximal to aganglionic segment – MEGACOLON
▪ Diagnosis - absence of ganglion cells (MEISSNER submucosal
and AUERBACH myenteric plexus) in muscle wall &
submucosa of non-distended bowel
Inadequate motility of part of the intestine,

Acquired CAUSES – MEGACOLON

▪Chagas disease – Trypanosoma cruzi destroys enteric
plexus
▪Organic bowel obstruction – neoplasm,
inflammatory stricture
▪Toxic megacolon – complicates ulcerative
colitis/Crohn disease
 SALMONELLA
▪ Typhoid fever
▪ Etiology – S. typhi, S. paratyphi
▪ Source – contaminated food, water
▪ Acute infection – abdominal pain, vomiting, bloody
diarrhea, fever
▪ Blood culture - positive
▪ Later - organism enters Peyer's patches (ileum)and RE
system – ulceration of Peyer patches – longitudinal, oval
ulcers - bleeding, perforation
SALMONELLOSIS

• Systemic dissemination – typhoid fever

– involvement of macrophages –
splenomegaly
▪ Gall bladder colonization –
chronic carrier state complications
• Children with sickle-cell anemia
susceptible to develop Salmonella
osteomyelitis.
 TUBERCULOSIS

▪ Predominantly involves small intestine

▪ Mycobacterium bovis – contaminated milk - now rare
▪ Secondary tuberculous enteritis – complication of
extensive pulmonary TB – swallowing infectious
sputum - caseous ulcers in ileum, ileocecal region –
transverse ulcers – healing by fibrosis – strictures
(‘napkin ring’ stricture)
 Pseudomembranous colitis
• Pseudomembranous colitis- antibiotic associated
colitis
– during or after course of antibiotic
– Caused by clostridium difficile as well
as salmonella
yellow-tan mucosal membranes
– Antibiotics causes disruption of normal colonicswelling or
microbial flora and allows overgrowth of C. inflammation of the
large intestine (colon)
difficile due to an overgrowth of
Clostridioides difficile
– Colitis is associated with formation of (C difficile) bacteria.
pseudomembranes made of inflammatory cells
and debris at sites of mucosal injury
 Parasitic enteritis
• Giardia lamblia - Flagellated protozoa
• Transmission by feco-oral route , ingestion of cysts
(resistant to chlorine)
• Causes microvillous damage and apoptosis of small
intestinal epithelial cells.
• They are noninvasive and are identified in duodenal
biopsy by their characteristic pear-shaped organism

Giardia lamblia attaches to small intestinal

mucosa do not invade
AMOEBIC DYSENTERY.
• Entamoeba histolytica.
• prevalent in the tropical countries
• Common in large intestine
• Infection occurs from ingestion of cyst
• The cyst wall is dissolved in the small intestine from
where the liberated amoebae pass into the large
intestine.
• They invade the epithelium of the mucosa-submucosa -
characteristic flask-shaped ulcers.
• The trophozoites of Entamoeba
are seen in the inflammatory exudate

• Intestinal amoebae characteristically have ingested

red cells in their cytoplasm.

Complications:
• amoebic liver abscess or amoebic hepatitis,
• perforation, hemorrhage
• amoeboma which is a tumor-like mass.
 MALABSORPTION
CLINICAL MANIFESTATION
▪ Chronic diarrhea, steatorrhea (excess fecal fat – greasy,
frothy, bulky stools)
- hallmark of malabsorption
▪ Weight loss
▪ Anemia (malabsorption of iron, folate, vitamin B12)
▪ Musculoskeletal – osteopenia - ↓ calcium, vitamin D,
proteins
▪ Endocrine – eg: secondary hyperparathyroidism due to
↓ calcium * villi atrophy
▪ Skin – purpura, petechiae crypt hyperplasia
increased intraepithelial lymphocytes*
▪ Nervous system involvement
mucosal inflammation
 CELIAC DISEASE
NONTROPICAL SPRUE
▪ Celiac sprue or gluten-sensitive enteropathy
▪ Non-infectious cause for malabsorption
▪ Caucasian disease, genetic factors+ (HLA-B8)
▪ Sensitivity to protein component of wheat -
gluten
autoimmune disorder
▪ T-cell mediated chronic inflammatory reaction -
? triggered by viral infection
• Endoscopy – proximal small
intestine(duodenum, proximal jejunum)
• – FLAT MUCOSA
• Clinical – infancy to mid-adulthood, diarrhea,
malnutrition
 TROPICAL SPRUE
(TROPICAL ENTEROPATHY)

▪ Celiac-like disease, occurs exclusively in people

living in / visiting the tropics
▪ Infectious cause for malabsorption – ? E.coli
▪ Injury at all levels of small intestine
▪ Mic – severe diffuse enteritis, villus flattening,
megaloblastic changes in epithelial cell nuclei (B12,
folate deficiency)
▪ Clinical – chronic diarrhea, weight loss, macrocytic
anemia
 IDIOPATHIC (CHRONIC) INFLAMMATORY
BOWEL DISEASE
▪ Abnormal immune response against normal gut flora &
self- antigens – T cells, TNF alpha

▪ GENETIC SUSCEPTIBILITY
▪ HLA associations – HLA –DR1 (CD), HLA-DR2 (UC)
▪ Crohn’s disease – mutations in NOD2 gene

Females > males, peak age – 20 – 25 years

 CROHN DISEASE
EPIDEMIOLOGY
▪ Primarily in Western developed countries
▪ Smoking – strong exogenous risk factor
▪ GIT manifestations (anywhere from mouth to anus –
especially terminal ileum, ileocecal valve, cecum) +
systemic manifestations
▪ Old term - “terminal ileitis” or “regional enteritis”
(abnormal bowel segments with normal “skip” areas)
CROHN DISEASE :GROSS
▪ CD – autoimmune, involves esophagus –
anus, more in distal small intestine &
colon
▪ Serosa – granular, dull gray
▪ Focal mucosal ulcers (aphthous ulcers) Mucosa – “Cobblestone”
appearance
– join to form linear serpentine ulcers,
▪ Fissures (deep, can perforate), fistulae,
sinuses
▪ “Skip lesions”
▪ “Creeping fat” around bowel
▪ Intestinal wall – rubbery, thick (edema ,
inflammation, fibrosis)
▪ X-ray – “string” sign appearance
 CROHN DISEASE
Crohn’s shows rectal sparing,
MICROSCOPY whereas Ulcerative Colitis
always involves the rectum.
▪ Mucosal ulcers, neutrophilic
infiltration
▪ Crypt abscesses (CA) affects all of the layers of
the bowel LA
▪ Transmural inflammation,
CA
lymphoid aggregates (LA) in
Only Crohn’s has
bowel wall muscularis and serosa
involvement.
▪ Noncaseating granulomas (GR)
▪ Chronic mucosal damage –
blunting of villi GR
do not have a central
region of necrosis and
occur more commonly.
 CD - COMPLICATIONS
INTESTINAL
Only GALS can be Crones (Crohn’s).

▪ Fibrosing strictures (terminal ileum - obstruction),

• Fistulae (to bowel, bladder, vagina), sinuses
▪ Generalized malabsorption
▪ Protein losing enteropathy
▪ Malabsorption of vit. B12 - pernicious anemia
▪ Steatorrhea – malabsorption of bile salts
 ULCERATIVE COLITIS
▪ UC – chronic inflammatory disease limited
to colon and rectum
GROSS
▪ Severe pancolitis, no “skip” lesions
▪ Distal ileum involved – “backwash ileitis”
▪ Disease limited to mucosa & submucosa
▪ Red, granular mucosa – later, ulceration
Pseudo polyps
▪ Very severe cases –toxic damage to nerve
plexus & muscularis propria, swelling,
gangrene of colon TOXIC MEGACOLON
▪ X-ray – rigid ahaustral appearance of colon –
lead pipe sign
 ULCERATIVE COLITIS
MICROSCOPY

▪ Collections of neutrophils in crypts

– crypt abscesses
▪ Later, ulceration of mucosa
▪ Healed disease – submucosal
fibrosis, atrophy of
colonic glands
▪ Epithelial changes – dysplasia – low
grade to high grade - carcinoma
Atrophic colonic glands
 ACUTE APPENDICITIS
Etiology:
▪ associated with obstruction in 50 – 80 % of cases fecoliths.
▪ Lymphoid hyperplasia (viral infections), tumor, worms
▪ Specific inflammations – typhoid, TB, ulcerative colitis, Crohn’s disease

▪ COMPLICATIONS
▪ Inflammation in all layers of appendix – serosal inflammation – suppurative
appendicitis
▪ Ischemia – gangrenous appendix
▪ Perforation of appendix – peritonitis
▪ Rare – bacteremia, liver abscess
 Intestinal Polyps non-neoplastic
Hyperplastic Polyp
▪ Asymptomatic
▪ Majority located in the rectosigmoid,
▪ Composed of well-formed glands and
crypts lined by differentiated goblet or
absorptive cells.
▪ Pure hyperplastic polyps have no
malignant potential.
 HAMARTOMATOUS

JUVENILE POLYPS (Retention polyps)

• Children < 5 years,
• predominantly rectum
• Gross: large (1-3 cm. diameter),
usually single, rounded, smooth,
pedunculated
• Mic: lamina propria with cystically
dilated glands filled with mucus
• Clinical: rectal bleeding, infarction
 HAMARTOMATOUS POLYPS
PEUTZ-JEGHERS POLYPS
▪ Rare, autosomal dominant syndrome
▪ Multiple hamartomatous polyps throughout GIT +
melanotic mucosal & cutaneous pigmentation – lips, oral
mucosa, genitalia, hands -Peri-oral pigmented spots

▪ Gross: large, pedunculated

▪ Mic: connective tissue
+ smooth muscle + glands
▪ Clinical: Obstruction, Intussusception.
 Inflammatory Polyps

▪ Occur in patients with longstanding IBD,

especially in chronic ulcerative colitis.
▪ Represent an exuberant reparative
response to longstanding mucosal injury
called pseudo polyps
▪ Mic- connective tissue core
+Inflammatory cells+ cystically dilated
glands covered by regenerating
epithelium
• Lymphoid polyps

• Solitary or multiple tiny

elevated lesions
• Common in rectum, also called
rectal tonsils
• Micro- lymphoid follicles with
germinal centers located in
mucosa and submucosa
Neoplastic Polyps
Tubular adenoma
precancerous polyps in
your colon
Size: small (sessile) ,
large(pedunculated)
Micro - Stalk has a central
core of fibro-vascular tissue,
covered with dysplastic
colonic mucosa.regular growth
pattern
Severe dysplasia and invasive All degree of dysplasia with frank
carcinoma in about 5%
adenoma
Villous Adenoma Tubulovillous
adenoma
Size: 1 to 10 cm in diameter. Degree of dysplasia
Most are broad, sessile, velvety and malignant
lesions projecting 1 to 3 cm. potential is
Micro- intermediate between
Frondlike papillary projections of tubular and villous
adenomatous epithelium with a adenomas.
delicate fibrovascular core.
invasive carcinoma in up to 40%.
 Neoplastic Polyps
Clinical features
• The smaller adenomas are usually asymptomatic,
occult bleeding.
can be seen
• Villous adenomas are much more frequently
symptomatic because of overt or occult rectal
bleeding or mucoid material rich in protein and
potassium to produce hypoproteinemia or
hypokalemia.
• Adenomas in the immediate vicinity of the
ampulla of vater may produce biliary obstruction.
located where your bile duct and pancreatic duct join and empty into your small intestine.
 Relationship of Neoplastic Polyps to Carcinoma

• Adenoma to carcinoma sequence is documented by

several observations and genetic alterations.

• The probability of carcinoma occurring in a neoplastic

polyp is related to:
1. The size of the polyp.
2. The relative proportion of its villous features.
3. The presence of significant cytological atypia
(dysplasia) in the neoplastic cells.
 Familial Polyposis Syndrome
▪ Patients have genetic tendencies to develop neoplastic polyps, most
often autosomal dominant.
▪ Familial polyposis coli (FPC) extra-clonic features not as common
▪ Genetic defect – APC gene mutation
▪ Innumerable neoplastic polyps in the colon (500 to 2500)
▪ Polyps are also found elsewhere in alimentary tract
▪ Most polyps are tubular adenomas
▪ The risk of colorectal cancer is 100% by midlife.
▪ Gardener’s syndrome
▪ Polyposis coli, multiple osteomas, epidermal cysts, and fibromatosis.
▪ Turcot syndrome
▪ Polyposis coli, glioma and fibromatosis
Colon cancer predisposition syndrome characterized by hundreds to
thousands of precancerous colon polyps.
Develop polyps at very young ages.
Caused by mutations in the APC gene.
Hundreds of polyps in colon Three tubular adenomas in a single
microscopic field
 Hereditary non-polyposis colonic
cancer(HNPCC)
▪ Lynch syndrome
▪ Autosomal dominant
▪ germ-line mutations of DNA mismatch repair
genes like MSH2 or MLH1.
▪ Occurs in younger age < 50 years
▪ Associated with other primary cancers like
endometrial ca , ovarian ca ,etc.
“Nonpolyposis” means that colorectal
cancer can occur when only a small
number of polyps are present
Dietary factors:
- Low content of unabsorbable vegetable fibre.
- High content of refined carbohydrates.
- High fat content.
- Increased intake of nitrites, nitrates
(nitrosamines).
- Reduced intake of vit A, C & E.
Adenoma – carcinoma sequence:
Increased risk of malignancy
a) Increased Number of adenomas- familial polyposis coli
b) Size- large size
c)Type of adenoma - villous component
 Colorectal carcinogenesis

• Two pathogenetically distinct pathways both result

from
accumulation of multiple mutations

– The APC/B-catenin pathway

– Microsatellite instability (MSI) Mechanism
Defective DNA mismatch repair (TGF-β receptor gene
and BAX gene )
 Colorectal Carcinoma
Morphology
▪ Proximal colon (ascending colon) –
polypoid, exophytic
mass lesions protruding into the lumen from the mucosal surface
▪ Distal colon (descending) –
annular encircling lesions –
napkin-ring constriction of bowel
 CA COLON
MICROSCOPY

▪ Well-differentiated to Undifferentiated adenocarcinoma

▪ Signet-ring appearance seen mucinous adenocarcinoma
▪ Carcinomas in anal zone – squamous cell carcinomas

Malignant glands

Muscle layer
 Colorectal Carcinoma

▪ Clinical features

Left-sided lesions
▪ -present earlier – obstruction and change in bowel
habits.
▪ Poorer prognosis- infiltrative growth pattern
Right-sided lesions
▪ present with weakness, malaise, weight loss,
unexplained anaemia (secondary to early bleeding).
 CA COLON - DIAGNOSIS
➢ Digital rectal testing proteins produced by some types of cancer.

➢ Fecal testing for occult blood loss

➢ Sigmoidoscopy, colonoscopy, Contrast CT
➢ Serum markers – carcinoembryonic antigen (CEA)
➢ - related to tumour size and extent of spread.
➢ - helpful in monitoring for recurrence of tumour
after resection.
➢ Pitfalls of CEA – not sensitive, not specific (may be +
in ca lung, breast, ovary, pancreatitis, ulcerative
colitis etc)
 TNM STAGING OF COLORECTAL CANCER – BASED ON DEPTH OF
INVASION

Tis – T1 – tumor
carcinoma invades
in situ submucosa

T2 – tumor
extends into T3 –
muscularis invasion
propria
of
subserosa

T4 – invasion into adjacent organs/peritoneum N0, N1, N2 – M0, M1