Git pathology lecture

 CONGENITAL ANOMALIES
 ESOPHAGUS
 STOMACH
 SMALL INTESTINE
 COLON
 PERITONEUM

 ATRESIA
 FISTULA
 DUPLICATIONS
 DIAPHRAGMATIC HERNIA
 ECTOPIA
 MECKEL’S DIVERTICULA
 PYLORIC STENOSIS
 HIRSCHSPRUNG DISEASE

 DIFFERENCE BETWEEN AGENESIS(NOT
FORMED) AND ATRESIA (INCOMPLETE
DEVELOPMENT)
 ATRESIA OFTEN ASSOCIATED WITH FISTULA
EX-ESOPHAGEAL ATRESIA WITH
TRACHEOESOPHAGEAL FISTULA/DUODENAL
ATRESIA/IMPERFORATE ANUS
 STENOSIS-LUMEN REDUCED PARTIAL OR
COMPLETE

 OMPHALOCOELE-CLOSURE OF ABDOMINAL
MUSCULATURE INCOMPLETE
 GASTROSCHISIS-INVOLVES ALL LAYERS OF
ABDOMINAL WALL FROM PERITONEUM TO SKIN

 ECTOPIC GASTRIC MUCOSA –INLET PATCH
 ECTOPIC PANCREATIC MUCOSA
 GASTRIC HETEROTOPIA

 Congenital abnormality of small intestine
resulting from persistence of
omphalomesenteric duct (vitelline duct)
 It is true diverticulum ( containing al three
layers of bowel wall )

 Vitelline duct or omphalomesenteric duct
anomalies are secondary to the persistence
of the embryonic vitelline duct, which
normally obliterates by weeks 5–9 of
intrauterine life
 Meckel’s diverticulum is the most common
vitelline duct anomaly

During week 3 of gestation, the mid gut is open
into the yolk sac, which does not grow as
rapidly as the rest of the embryo.
Subsequently, by week 5, the connection
with the yolk sac becomes narrowed and is
then termed a yolk stalk, vitelline duct, or
omphalomesenteric duct. Normally, the
vitelline duct disappears by gestational week
9, just before the mid gut returns to the
abdomen

 Meckel diverticulum ( rule of two)
 Occur in 2% of population
 2 inch long
 2 feet from ileocecal valve
 In child younger than age2
 2 type of tissue ( ectopic stomach or
pancreas )
 not attached to the abdominal wall

but it is one of the most unlikely to cause
symptoms. About 4% of children with a
Meckel’s diverticulum develop symptoms,
and more than 60% of those who develop
symptoms are younger than 2 years of age.2–
5 The male-to-female complication rate ratio
is about 3:1

 Most complications of these abnormalities
are related to ectopic tissue (gastric,
pancreatic, colonic, endometriosis, or
hepatobiliary) . Ectopic gastric tissue usually
causes bleeding from ulceration of the
adjacent ileal mucosa. The ileal mucosa is
not equipped to buffer the acid produced by
the ectopic gastric mucosa and thus is prone
to ulceration. ulceration. The site of the
ulceration is most often at the junction of
the
normal ileal mucosa and the ectopic gastric
mucosa

 Intestinal obstruction may be caused by a
Meckel’s diverticulum attached to the
umbilicus by a fibrous cord or by a fibrous
cord between the ileum and the umbilicus
and can also occur by intussusception with
the diverticulum

 Ulceration
 Hemorrhage
 Small bowel obstruction
 Diverticulitis
 Perforation

 The classic presentation is an older infant or
young child with painless rectal bleeding
(This usually consists of a large volume of
bright red bleeding but can occasionally also
present as dark, tarry stools)
 Malena may be episodic and usually ceases
without treatment; sometimes the malena is
insidious and not appreciated by the family.
In a young child with haemoglobin positive
stools and a chronic iron deficiency anemia,
the diagnosis of Meckel’s diverticulum
should be considered

 Intestinal obstruction, usually due to
intussusception, is the most typical
presentation in newborns and infants. The
symptoms include crampy abdominal pain,
bilious vomiting, currant-jelly stools, and
abdominal distention

 intestinal ischemia, such as acidosis,
peritonitis, and shock, may occur first, and
can be fatal in infants.

 Patients with Meckel’s diverticulitis often
have symptoms that resemble appendicitis.
They are usually older children. Peri-
umbilical pain is the first symptom. They
usually do not have the same amount or
intensity of vomiting and nausea

 Diagnosis of a symptomatic vitelline duct
malformation is dependent on the anatomic
configuration and its presentation, signs, and
symptoms. History and physical examination
are important for the diagnosis
 A complete description of the quality and
frequency of the bloody stools is necessary in
patients with rectal bleeding. Rectal
examination and lower endoscopy is useful to
identify other causes of lower bleeding

 The test of choice for a bleeding Meckel’s
diverticulum is a (Meckel’s scan), which
concentrates the isotope in ectopic gastric
mucosa

 If obstruction from either intussusception or
volvulus is suspected, plain x-rays may reveal
dilated bowel loops and multiple air-fluid
levels.

 Symptomatic children with
omphalomesenteric duct remnants should
be resuscitated before intervention. Those
with significant hemorrhage should be
transfused
 The incision chosen varies with the symptoms
and the age of the patient

o Children with Meckel’s diverticulitis or a
bleeding Meckel’s diverticulum are operated
on by using a transverse appendectomy
incision with medial extension if necessary.
Patients with suspected intestinal
obstruction should be explored through a
generous laparotomy incision.

 Hallmark is non-bilious vomiting
 Other signs include abdominal distention and
bleeding from secondary inflammation
 Most common cause of non-bilious vomiting
is infantile hypertrophic pyloric stenosis

 First described by Hirschsprung in 1888
 Ramstedt described an operative procedure
to alleviate the condition in 1907 – the
procedure used to this day to treat pyloric
stenosis

 3/1000 live births – frequency may be
increasing
 Most common in whites of Northern
European ancestry, less common in
African Americans and rare in Asians
 Four times more common in males –
especially firstborn
 Increased in infants with type B or O
blood groups
 Associated with other congenital defects
incl TEF

 Cause is unknown, but abnormal muscle
innervation, breast feeding and maternal
stress in the 3rd trimester have been
implicated
 Elevated serum PG’s, reduced levels of
pyloric nitric oxide synthase and infant
hypergastrinemia have been found

 Non-bilious vomiting is the initial symptom
 May or may not be projectile initially
 Usually progressive, occurs immediately after
a feeding
 Vomiting usually starts after 3 wks of age,
but may develop as early as 1st week and as
late as the 5th month

 After vomiting, infant is hungry and wants to
feed again
 Progressive loss of fluid, hydrogen ion and
chloride leads to a hypochloremic metabolic
alkalosis.
 Serum K levels are maintained
 Greater awareness has led to earlier
diagnosis

 Jaundice occurs in 5% of infants with pyloric
stenosis – associated with a decreased level
of glucuronyl transferase

 Diagnosis traditionally made by palpation
of mass
 Firm, movable, approx 2 cm in length,
olive shaped and best palpated from the
left
 Mass located above and to the right of the
umbilicus in the midepigastrum beneath
the liver edge
 Peristaltic wave may be present prior to
emesis

 Straightforward if olive is present
 Difficult to distinguish from GERD esp in
early stages
 UGI or US can be used – but US has
become the standard at most centers
 Ultrasound – Sensitivity of 90%
 Criteria for diagnosis – pyloric muscle
thickness greater than 4 mm and an
overall pyloric muscle length greater than
14mm

 US pitfalls – pylorospasm may mimic those
of PS, potential false-pos and false-
negative readings
 UGI – classic signs are elongated pyloric
canal, the “double tract” sign (parallel
streaks of barium in the narrowed
channel, and the “shoulder sign”(bulge of
pyloric muscle into the antrum).
 Main pitfall of UGI is radiation exposure

 Infants who are reactive to external
stimulation, those fed by inexperienced
caretakers, or those for whom adequate
maternal-infant bonding has not been
established may vomit frequently in the early
weeks of life.
 GERD with or without a hiatal hernia may be
confused with PS esp in the early stages

 Inborn errors of metabolism may produce
recurrent emesis with alkalosis or acidosis
and lethargy, coma or seizures.
 Salt-losing CAH presents with prominent
vomiting shortly after birth. Females will be
virilized, but the genitals appear normal in
males. Acidosis and hyperkalemia usually
present.

 Vomiting with diarrhea suggests
gastroenteritis.
 Always have to think of increased ICP,
subdural hematoma
 Systemic infections can also cause persistent
vomiting.

 Preoperative treatment is directed toward
correcting the fluid/acid-base and
electrolyte imbalances.
 Correction of the alkalosis is essential to
prevent postoperative apnea
 Surgery is the treatment of choice –
Ramstedt pyloromyotomy

 Ramstedt pyloromyotomy – performed
through a short transverse incision or
laparoscopically
 Underlying pyloric mass is split without
cutting the mucosa and the incision is
closed
 Post-op vomiting occurs in ½ the patients
and thought to be due to edema of the
pylorus
 Feedings can usually be initiated within
12-24 hours

 Persistent vomiting suggests an incomplete
pyloromyotomy, gastritis, GERD.
 Surgical treatment is curative with a low
mortality rate

• Hirschsprung’s disease is the most common cause of
lower intestinal obstruction in neonates.
• Hirschsprung’s disease (aganglionic megacolon) is
a congenital anomaly caused by migratory
failure of neural crest cells leading to abnormal
innervations of the bowel.
• The defect begins in the internal anal sphincter
and extends proximally for a variable length of
gut

 INCIDENCE: 15000 live birth newborn
 70-80% is boys. (M / F. 4: 1 )
 Less common in blacks.

 The fundamental pathology in HD is the absence of
ganglion cells in the submucosal and intermuscular
nerve plexuses and is associated with an increase in
the nerve fibers in the affected segment .
 That aganglionic segment usually involves the
terminal intestine, i.e. the rectum or recto sigmoid.
The aganglionic segment may, however, include the
entire large bowel and even small bowel..

 The colon proximal to the aganglionic
segment, in an effort to overcome the partial
obstruction, becomes distended and its wall
markedly thickened because of muscle
hypertrophy
 The degree of hypertrophy and dilatation
depends upon the duration and degree of
obstruction and thus, indirectly to the age of
the patient.

1. Congenital : This type is the commonest one .
 Etiology of the disease is still unknown .but Genetic
factors are now identified.
 10% of cases have familial history, especially those with
long segment disease.
2. Acquired :
Degeneration of the ganglions may occur due to:
-Vascular causes like after pull through procedure
due to ischemia & tension.
- Non vascular causes like
Trypanosoma (chaga's disease).
Vitamin B1 def.
Chronic infection ( TB.).

 HD is usually a solitary anomaly in a full term,
otherwise healthy infant
 Associated anomalies do occur in nearly 20% of cases
 urogenital system (11%)
 cardiovascular system (6%)
 gastrointestinal system (6%),
 with 8% having various other malformations
 Prematurity is reported in as many as 10% of those
children with HD
 Trisomy 21 occurs in approximately 5% of cases

1. Failure to pass meconium in the
1st 24h of life
98% of neonates pass meconium in the first 24 hours
of age.. Any newborn who fails to pass meconium in
the first 24-48 hours of life should be evaluated for
possible Hirschsprung's disease.
2. Neonatal Intestinal obstruction
symptoms include bilious vomiting, abdominal
distension and refusal to feed.
3. Recurrent Enterocolitis
mainly in the 1st three months of life.

4. TOXIC MEGACOLON :
Fever.
Abdominal distension.
Bile stained vomitus.
Explosive diarrhea.
Dehydration.
Shock.
5. Spontaneous perforation occurs in
3%,specially if long segment aganglionosis.
6. Chronic constipation patients may have
chronic constipation in response to changes
in feeding. And may have Growth
retardation. Multiple fecal masses on
abdominal examination.

History
failure to pass meconium,
painless abdominal distension &
constipation)
Physical examinations
Distended abdomen with
Multiple fecal masses on
abdominal examination
on DRE characteristically there is
 Anal sphincter is hypertonic
 Rectum is typically empty.
 Hard fecal mass.

Radiology
1. Plain x-rays of the abdomen :Erect & supine
2. Contrast Enema.
Shows narrow distal segment, funnel-shaped
dilatation at level of transition zone with
marked dilatation of the proximal colon.
24-hrs delayed films is important in diagnosis; it
shows poor emptying with barium throughout
the colon, as opposed to the child with
psychogenic stool holding in whom the barium
generally collects in the distal recto sigmoid.

Rectal biopsy :
 Rectal biopsy is the definitive
diagnostic test and demonstrates
absence of ganglion cells, nerve
hypertrophy and stains indicating
increased acetyl cholinesterase
activity.
 suction mucosal biopsy (at
different levels ). Can be done
without anesthesia
 full thickness biopsy is done under
general anesthesia.

Electromanometry :
 not useful in neonate
 excellent screening tool in infant &
children .
 The classic finding is the absence of
the recto anal inhibitory reflex
when the rectum is distended.
 A balloon is inflated in the rectum to
measure pressure in the area
UltraSonography: for associated anomalies

Treatment:
 Decompression: introduce a rectal tube and
irrigation
 Colostomy
 Definitive procedures
 Closing of the stoma

 Chronic constipation :
 laxative
 saline enema.
 Work up to establish the diagnosis
 then the definitive treatment will be planned
Open surgery :
There are many surgical options for Pull-through
operation. All aiming at resection of aganglionic
segment and anastomosing the two normal ganglionic
ends. They give excellent result in 90%.
a.swenson.
b.soave.
c.Rehbein.
d. Duhamel.
e. Boley's

Treatment
Transanal Endorectal Pull-Trough
 It can be performed safely in infant as well
 Generally one-stage surgery
 No abdominal phase
 The anastomosis is happening in a „safe”
place at the pectinate line

1. anastomotic leak.
2. stricture .
3. retraction of the colon.
4. fecal incontinence (soiling or encopresis ).
5. persistent constipation

Hirschsprung’s DiseaseFunctionalConstipationFeature
At birth2-3 yearsOnset
CommonRareDelayed passage of meconium
CommonRareObstructive symptoms
RareCommonWithholding behavior
RareCommonFear of defecation
RareCommonFear of incontinence
Small, ribbon-likeVery largeStool size
CommonRarePoor growth
PossibleNeverEnterocolitis
NarrowedEnlargedRectal ampulla
RareCommonStool in ampulla
Transitional zone, delayed
emptying
Lg amount of stools,
no transitional zone
Barium enema
Absent rectosphincteric refl exNormalAnorectal manometry
No ganglion cells, nerve hypertrophy
and increase acetylcholinesterase
activity
NormalRectal biopsy

 It is a hollow, highly distensible muscular
tube that extends from the epiglottis to the
gastroesophageal junction, located just
above the diaphragm.

 OBSTRUCTIVE AND VASCULAR DISEASES
 ESOPHAGITIS
 ESOPHAGEAL TUMORS

 MECHANICAL-STENOSIS/ AGENESIS/
ESPHAGEAL WEB/LYE STRICTURES
 FUNCTIONAL-NUT CRACKER
ESOPHAGUS/DIFFUSE ESOPHAGEAL
SPASM/ACHALASIA CARDIA

 ESOPHAGEAL VARICES- dilated splanchno
systemic junctional veins in esophagus

 PATHOGENESIS One of the few sites where the
splanchnic and systemic venous circulations can
communicate is the esophagus.
 Thus, portal hypertension induces development
of collateral channels that allow portal blood to
shunt into the caval system.
 However, these collateral veins enlarge the
subepithelial and submucosal venous plexi within
the distal esophagus.
 These vessels, termed varices, develop in 90%
of cirrhotic patients, most commonly in
association with alcoholic liver disease.
 Worldwide, hepatic schistosomiasis is the second
most common cause of varices

 MORPHOLOGY Varices can be detected by
angiography and appear as tortuous dilated
veins lying primarily within the submucosa of
the distal esophagus and proximal stomach.
 Varices may not be obvious on gross
inspection of surgical or postmortem
specimens, because they collapse in the
absence of blood flow .
 The overlying mucosa can be intact but is
ulcerated and necrotic if rupture has
occurred.

 Clinical Features Varices often are
asymptomatic, but their rupture can lead to
massive hematemesis and death.
 Variceal rupture therefore constitutes a
medical emergency.

 Lacerations- Mallory Weiss tear/ boerhaave
syndrome
 Chemical and Infectious Esophagitis
 Reflux esophagitis
 Eosinophilic esophagitis
 Barrett’s esophagus

 Often associated with severe retching or vomiting, as
may occur with acute alcohol intoxication.
 Normally, a reflex relaxation of the gastroesophageal
musculature precedes the antiperistaltic contractile
wave associated with vomiting.
 This relaxation is thought to fail during prolonged
vomiting, with the result that refluxing gastric
contents overwhelm the gastric inlet and cause the
esophageal wall to stretch and tear.
 Patients often present with hematemesis.
 The roughly linear lacerations of Mallory-Weiss
syndrome are longitudinally oriented, range in length
from millimetres to several centimeters, and usually
cross the gastroesophageal junction.
 These tears are superficial and do not generally
require surgical intervention

 Boerhaave syndrome, characterized by
transmural esophageal tears and
mediastinitis, occurs rarely and is a
catastrophic event.

 The stratified squamous mucosa of the
esophagus may be damaged by a variety of
irritants including alcohol, corrosive acids or
alkalis, excessively hot fluids, and heavy
smoking.
 Infectious esophagitis may occur in otherwise
healthy persons but is most frequent in those
who are debilitated or immunosuppressed

 The stratified squamous epithelium of the
esophagus is resistant to abrasion from foods but
is sensitive to acid.
 The submucosal glands of the proximal and
distal esophagus contribute to mucosal
protection by secreting mucin and bicarbonate.
 More important, constant LES tone prevents
reflux of acidic gastric contents, which are under
positive pressure.
 Reflux of gastric contents into the lower
esophagus is the most frequent cause of
esophagitis . The associated clinical condition is
termed gastroesophageal reflux disease (GERD.

 MORPHOLOGY --- Simple hyperemia, may be
the only alteration. In mild GERD the
mucosal histology is often unremarkable.
 With more significant disease, eosinophils
are recruited into the squamous mucosa,
followed by neutrophils, which usually are
associated with more severe injury .
 Basal zone hyperplasia exceeding 20% of
the total epithelial thickness and elongation
of lamina propria papillae, such that they
extend into the upper third of the
epithelium, also may be present.

 The most frequently reported symptoms are
heartburn, dysphagia, and, less often,
noticeable regurgitation of sour-tasting
gastric contents.
 Rarely, chronic GERD is punctuated by
attacks of severe chest pain that may be
mistaken for heart disease.

 Food impaction and dysphagia in adults and
feeding intolerance or GERD-like symptoms
in children.
 The cardinal histologic feature is epithelial
infiltration by large numbers of eosinophils,
particularly superficially and at sites far
from the gastroesophageal junction.
 Treatments include dietary restrictions to
prevent exposure to food allergens, such as
cow milk and soy products, and topical or
systemic corticosteroids.

 Barrett esophagus is a complication of
chronic GERD that is characterized by
intestinal metaplasia within the esophageal
squamous mucosa.
 Males are affected most often and typically
present between 40 and 60 years of age.
 The greatest concern in Barrett esophagus is
that it confers an increased risk of
esophageal adenocarcinoma.

 Barrett esophagus is recognized endoscopically
as tongues or patches of red, velvety mucosa
extending upward from the gastroesophageal
junction.
 This metaplastic mucosa alternates with residual
smooth, pale squamous (esophageal) mucosa
proximally and interfaces with light-brown
columnar (gastric) mucosa distally .
 Goblet cells, which have distinct mucous
vacuoles that stain pale blue by H&E and impart
the shape of a wine goblet to the remaining
cytoplasm, define intestinal metaplasia and are
a feature of Barrett esophagus

 Adenocarcinoma
 Squamous cell carcinoma

 Esophageal adenocarcinoma typically arises
in a background of Barrett esophagus and
long-standing GERD.
 Risk of adenocarcinoma is greater in patients
with documented dysplasia and is further
increased by tobacco use, obesity, and
previous radiation therapy.
 Esophageal adenocarcinoma occurs most
frequently in whites and shows a strong
gender bias, being seven times more
common in men than in women

 PATHOGENESIS Molecular studies suggest that the
progression of Barrett esophagus to adenocarcinoma
occurs over an extended period through the stepwise
acquisition of genetic and epigenetic
 changes.
 This model is supported by the observation that
epithelial clones identified in non dysplastic Barrett
metaplasia persist and accumulate mutations during
progression to dysplasia and invasive carcinoma.
 Chromosomal abnormalities and TP53 mutation are
often present at early stages of esophageal
adenocarcinoma.
 Additional genetic changes and inflammation also
are thought to contribute to neoplastic progression.

 MORPHOLOGY
 Esophageal adenocarcinoma usually occurs in the
distal third of the esophagus and may invade the
adjacent gastric cardia .
 While early lesions may appear as flat or raised
patches in otherwise intact mucosa, tumors may
form large exophytic masses, infiltrate diffusely,
or ulcerate and invade deeply.
 On microscopic examination, Barrett esophagus
frequently is present adjacent to the tumor.
Tumors typically produce mucin and form glands

 CLINICAL FEATURES pain or difficulty in
swallowing, progressive weight loss, chest
pain, or vomiting.
 As a result of the advanced stage at
diagnosis, the overall 5-year survival rate is
less than 25%.

 esophageal squamous cell carcinoma
typically occurs in adults older than 45 years
of age and affects males four times more
frequently than females.
 Risk factors include alcohol and tobacco
use, poverty, caustic esophageal injury,
achalasia, Plummer-Vinson syndrome,
frequent consumption of very hot beverages,
and previous radiation therapy to the
mediastinum.

 PATHOGENESIS
 A majority of esophageal squamous cell
carcinomas are at least partially attributable to
the use of alcohol and tobacco, the effects of
which synergize to increase risk.
 Nutritional deficiencies, as well as polycyclic
hydrocarbons, nitrosamines, and other
mutagenic compounds, such as those found in
fungus-contaminated foods, have been
considered as possible risk factors.
 HPV infection also has been implicated in
esophageal squamous cell carcinoma.
 The molecular pathogenesis of esophageal
squamous cell carcinoma remains incompletely
defined.

 In contrast to the distal location of most
adenocarcinomas,half of squamous cell
carcinomas occur in the middle third of the
esophagus .
 Squamous cell carcinoma begins as an in situ
lesion in the form of squamous dysplasia.
 Early lesions appear as small, gray-white
plaquelike thickenings.
 Over months to years they grow into tumor
masses that may be polypoid and protrude into
and obstruct the lumen.
 Other tumors are either ulcerated or diffusely
infiltrative lesions that spread within the
esophageal wall, where they cause thickening,
rigidity, and luminal narrowing.

 Clinical manifestations of squamous cell
carcinoma of the esophagus begin insidiously
and include dysphagia, odynophagia (pain on
swallowing), and obstruction.
 As with other forms of esophageal
obstruction, patients may unwittingly adjust
to the progressively increasing obstruction by
altering their diet from solid to liquid foods.
 Extreme weight loss and debilitation result
from both impaired nutrition and effects of
the tumor itself. Haemorrhage and sepsis
may accompany tumor ulceration

 INFLAMMATORY DISEASE OF THE STOMACH
 NEOPLASTIC DISEASE OF THE STOMACH

 The stomach is divided into four major anatomic
regions: the cardia, fundus, body, and antrum.
 The cardia is lined mainly by mucin-secreting
foveolar cells that form shallow glands.
 The antral glands are similar but also contain
endocrine cells, such as G cells, that release
gastrin to stimulate luminal acid secretion by
parietal cells within the gastric fundus and body.
 The well-developed glands of the body and
fundus also contain chief cells that produce and
secrete digestive enzymes such as pepsin.

 ACUTE GASTRITIS
 ACUTE PEPTIC ULCER
 CHRONIC GASTRITIS
 PEPTIC ULCER DISEASE

 Transient mucosal inflammatory process that
may be asymptomatic or cause variable
degrees of epigastric pain, nausea, and
vomiting.
 In more severe cases there may be mucosal
erosion, ulceration,
hemorrhage,hematemesis, melena, or, rarely,
massive blood loss

Damaging Forces:
1.Gastric acidity &
2. Peptic enzymes
Defensive Forces:
1.Surface mucus secretion
2.Bicarbonate secretion into mucus
3.Mucosal blood flow
4.Apical surface membrane transport
5.Epithelial regenerative capacity
6.Elaboration of prostaglandins

 H. pylori infection
 NSAID
 Aspirin
 Cigarettes
 Alcohol
 Gastric hyperacidity
 Duodenal-gastric reflux
 Ischemia
 Shock
 Delayed gastric
 emptying
 Host factors

 The lamina propria shows only moderate edema
and slight vascular congestion.
 The surface epithelium is intact, although
scattered neutrophils may be present.
 With more severe mucosal damage, erosion, or
loss of the superficial epithelium, may occur,
leading to formation of mucosal neutrophilic
infiltrates and purulent exudates.
 Hemorrhage also may occur, manifesting as dark
puncta in an otherwise hyperemic mucosa.
 Concurrent presence of erosion and hemorrhage
is termed acute erosive hemorrhagic gastritis

 Stress ulcers, most commonly affecting
critically ill patients with shock, sepsis, or
severe trauma
 Curling ulcers, occurring in the proximal
duodenum and associated with severe burns
or trauma
 Cushing ulcers, arising in the stomach,
duodenum, or esophagus of persons with
intracranial disease, have a high incidence of
perforation

 Acute ulcers are rounded and typically are less than
1 cm in diameter.
 The ulcer base frequently is stained brown to black
by acid digested extravasated red cells, in some
cases associated with transmural inflammation and
local serositis.
 Lesions may occur singly, more often multiple ulcers
are present within the stomach and duodenum.
 Acute stress ulcers are sharply demarcated, with
essentially normal adjacent mucosa, although there
may be suffusion of blood into the mucosa and
submucosa and some inflammatory reaction.
 Healing with complete re-epithelialization occurs
days or weeks after the injurious factors are
removed.

 Symptoms of gastric ulcers include nausea,
vomiting, and coffee-ground hematemesis.

 The symptoms and signs associated with chronic
gastritis typically are less severe but more
persistent than those of acute gastritis
 hematemesis is uncommon.
 The most common cause of chronic gastritis is
infection with the bacillus Helicobacter pylori.
 Autoimmune gastritis, the most common cause
of atrophic gastritis, represents less than 10% of
cases of chronic gastritis and is the most
common form of chronic gastritis in patients
without H. pylori infection.
 Less common causes include radiation injury and
chronic bile reflux.

 These spiral-shaped or curved bacilli are
present in gastric biopsy specimens from
almost all patients with duodenal ulcers and
a majority of those with gastric ulcers or
chronic gastritis.
 The increased acid secretion that occurs in
H. pylori gastritis may result in peptic ulcer
disease of the stomach or duodenum; H.
pylori infection also confers increased risk of
gastric cancer

 The incidence of H. pylori infection
correlates most closely with sanitation and
hygiene during an individual’s childhood
 H. pylori infection most often manifests as a
predominantly antral gastritis with high
acid production, despite hypogastrinemia
 Adhesins, which enhance bacterial
adherence to surface foveolar cells
 Toxins, such as that encoded by cytotoxin-
associated gene A (CagA), that may be
involved in ulcer or cancer development by
poorly defined mechanisms

 Four features are linked to H. pylori
virulence:
 Flagella, which allow the bacteria to be
motile in viscous mucus
 Urease, which generates ammonia from
endogenous urea, thereby elevating local
gastric pH around the organisms and
protecting the bacteria from the acidic pH of
the stomach.

 Gastric biopsy specimens generally
demonstrate H. Pylori in infected persons
 The organism is concentrated within the
superficial mucus overlying epithelial cells in
the surface and neck regions.
 Lymphoid aggregates, some with germinal
centres, frequently are present and
represent an induced form of mucosa-
associated lymphoid tissue (MALT) that has
the potential to transform into lymphoma

 Intestinal metaplasia, characterized by the
presence of goblet cells and columnar
absorptive cells, also may be present and is
associated with increased risk of gastric
adenocarcinoma.
 H. pylori shows tropism for gastric foveolar
epithelium and generally is not found in
areas of intestinal metaplasia, acid-
producing mucosa of the gastric body, or
duodenal epithelium
 An antral biopsy is preferred for evaluation
of H. pylori gastritis.

 Less than 10% of cases of chronic gastritis
 Typically spares the antrum and induces
hypergastrinemia
 Antibodies to parietal cells and intrinsic
factor that can be detected.
 Reduced serum pepsinogen I levels
 Antral endocrine cell hyperplasia
 Vitamin B12 deficiency
 Defective gastric acid secretion
(achlorhydria)

 Autoimmune gastritis is associated with loss
of parietal cells, which secrete acid and
intrinsic factor.
 Deficient acid production stimulates gastrin
release, resulting in hypergastrinemia and
hyperplasia of antral gastrin-producing G
cells.
 Lack of intrinsic factor disables ileal vitamin
B12 absorption, leading to B12 deficiency
and megaloblastic anemia (pernicious
anemia); reduced serum concentration of
pepsinogen I reflects chief cell loss.

 Autoimmune gastritis is characterized by diffuse
damage of the oxyntic (acid-producing) mucosa
within the body and fundus.
 Damage to the antrum and cardia typically is
absent or mild.
 With diffuse atrophy, the oxyntic mucosa of
the body and fundus appears markedly thinned,
and rugal folds are lost.
 Neutrophils may be present, but the
inflammatory infiltrate more commonly is
composed of lymphocytes, macrophages, and
plasma cells

 Antibodies to parietal cells and intrinsic
factor are present early in disease, but
pernicious anemia develops in only a
minority of patients.
 The median age at diagnosis is 60 years, and
there is a slight female predominance.
 Autoimmune gastritis often is associated
with other autoimmune diseases

 Peptic ulcer disease (PUD) most often is
associated with H. pylori infection or NSAID
use.
 In the US, the latter is becoming the most
common cause of gastric ulcers as H. Pylori
infection rates fall and low-dose aspirin use
in the aging population increases.
 PUD may occur in any portion of the
gastrointestinal tract exposed to acidic
gastric juices but is most common in the
gastric antrum and first portion of the
duodenum.

 Peptic ulcers are solitary in more than 80% of
patients.
 Lesions less than 0.3 cm in diameter tend to be
shallow, whereas those over 0.6 cm are likely to be
deeper.
 The classic peptic ulcer is a round to oval, sharply
punched-out defect .
 The base of peptic ulcers is smooth and clean as a
result of peptic digestion of exudate and on histologic
examination is composed of richly vascular
granulation tissue .
 Ongoing bleeding within the ulcer base may cause
life-threatening hemorrhage.
 Perforation is a complication that demands emergent
surgical intervention.

 Peptic ulcers are chronic, recurring lesions that
occur most often in middle-aged to older adults
without obvious precipitating conditions, other
than chronic gastritis.
 A majority of peptic ulcers come to clinical
attention after patient complaints of epigastric
burning or aching pain, although a significant
fraction manifest with complications such as iron
deficiency anemia, frank hemorrhage, or
perforation.
 The pain tends to occur 1 to 3 hours after meals
during the day, is worse at night, and is relieved
by alkali or food

A. Gastric Polyps-
1. Inflammatory and Hyperplastic Polyps
2. Fundic Gland Polyps
3. Gastric Adenoma
B. Gastric Adenocarcinoma.
C. Lymphoma
D. Carcinoid Tumor
E. Gastrointestinal Stromal Tumor

 Polyps, nodules or masses that project above
the level of the surrounding mucosa, are
identified in up to 5% of upper
gastrointestinal tract endoscopies

 The polyps frequently are multiple and
characteristically are ovoid in shape, less than 1 cm
in diameter, and covered by a smooth surface.
 On microscopic examination, polyps have irregular,
cystically dilated, and elongated foveolar glands.
 The lamina propria typically is edematous with
variable degrees of acute and chronic inflammation,
and surface erosions may be present.
 The frequency with which dysplasia, a precancerous
in situ lesion, develops in inflammatory or
hyperplastic polyps correlates with size; there is a
significant increase in risk in polyps larger than 1.5
cm.

 Fundic gland polyps occur sporadically and in
persons with familial adenomatous polyposis
(FAP) but do not have neoplastic potential.
 Their incidence has increased markedly as a
result of the use of proton pump inhibitors.
 This likely results from increased gastrin
secretion, in response to reduced acidity, and
glandular hyperplasia driven by gastrin.
 Fundic gland polyps may be asymptomatic or
associated with nausea, vomiting, or epigastric
pain.
 These well-circumscribed polyps occur in the
gastric body and fundus, often are multiple, and
are composed of cystically dilated, irregular
glands lined by flattened parietal and chief cells.

 10% of all gastric polyps
 Patients usually are between 50 and 60 years
of age
 Males are affected three times more often
than females
 Adenomas almost always occur on a
background of chronic gastritis with atrophy
and intestinal metaplasia
 The risk For development of adenocarcinoma
in gastric adenomas is related to the size of
the lesion and is particularly elevated with
lesions greater than 2 cm in diameter.

 Gastric adenomas are most commonly
located in the antrum and typically are
composed of intestinal-type columnar
epithelium ‘
 All gastrointestinal adenomas exhibit
epithelial dysplasia, which can be classified
as low- or high grade

 The most common malignancy of the
stomach
 More than 90% of all gastric cancer
 Early symptoms resemble those of chronic
gastritis, including dyspepsia, dysphagia, and
nausea
 Gastric cancer rates vary markedly with
geography
 Gastric cancer is more common in lower
socioeconomic groups and in persons with
multifocal mucosal atrophy and intestinal
metaplasia

 Gastric cancers are genetically heterogeneous
but certain molecular alterations are common.
 Mutations Germline mutations in CDH1, which
encodes E-cadherin, a protein that contributes
to epithelial intercellular adhesion, are
associated with familial gastric cancers, usually
of the diffuse type.
 patients with familial adenomatous polyposis
(FAP) who have germline mutations
adenomatous polyposis coli (APC) genes have
an increased risk of intestinal-type gastric
cancer.

 Sporadic intestinal-type gastric cancer is
associated with several genetic abnormalities
including acquired mutations of β-catenin, a
protein that binds to both E-cadherin and
APC protein; microsatellite instability; and
hypermethylation of genes including TGF
βRII, BAX, IGFRII, and p16/INK4a.
 TP53 mutations are present in a majority of
sporadic gastric cancers of both histologic
types.

 H. pylori: Chronic gastritis,
 H. pylori infection, promotes the
development and progression of cancers that
may be induced by diverse genetic
alterations in forms of chronic inflammation.
 H. pylori–induced chronic gastritis is
associated with increased production of pro
inflammatory proteins, such as interleukin-1β
(IL-1β) and tumor necrosis factor (TNF)

 EBV: Approximately 10% of gastric
adenocarcinoma are associated with Epstein-
Barr virus (EBV) infection.
 Morphologically, EBV-positive tumours tend
to occur in the proximal stomach and most
commonly have a diffuse morphology with
marked lymphocytic infiltration

 Gastric adenocarcinoma are classified according to
their location in the stomach as well as gross and
histologic morphology.
 The Lauren classification that separates gastric
cancers into intestinal and diffuse types correlates
with distinct patterns of molecular alterations, as
discussed above.
 Intestinal-type cancers tend to be bulky and are
composed of glandular structures similar to
esophageal and colonic adenocarcinoma.
 Intestinal-type adenocarcinoma typically grow along
broad cohesive fronts to form either an exophytic
mass or an ulcerated tumor.
 The neoplastic cells often contain apical mucin
vacuoles, and abundant mucin may be present in
gland lamina

 Diffuse gastric cancers display an infiltrative
growth pattern and are composed of discohesive
cells with large mucin vacuoles that expand the
cytoplasm and push the nucleus to the periphery,
creating a signet ring cell morphology
 These cells permeate the mucosa and stomach
wall individually or in small clusters.
 A mass may be difficult to appreciate in diffuse
gastric cancer, but these infiltrative tumours
often evoke a desmoplastic reaction that
stiffens the gastric wall and may cause diffuse
rugal flattening and a rigid, thickened wall that
imparts a “leather bottle” appearance termed
linitis plastica.

 Intestinal-type gastric cancer predominates
in high-risk areas and develops from
precursor lesions including flat dysplasia and
adenomas
 the incidence of diffuse gastric cancer is
relatively uniform across countries, there are
no identified precursor lesions, and the
disease occurs at similar frequencies in males
and females

 The depth of invasion and the extent of
nodal and distant metastasis at the time of
diagnosis remain the most powerful
prognostic indicators for gastric cancer.
 After surgical resection, the 5-year survival
rate for early gastric cancer can exceed 90%,
even if lymph node metastases are present

 Extranodal lymphomas can arise in virtually any
tissue, they do so most commonly in the
gastrointestinal tract, particularly the stomach
 In allogeneic hematopoietic stem cell and organ
transplant recipients,
 The bowel also is the most frequent site for
Epstein-Barr virus–positive B cell
lymphoproliferations.
 Nearly 5% of all gastric malignancies are primary
lymphomas, the most common of which are
indolent extra nodal marginal zone B cell
lymphomas.
 In the gut, these tumors often are referred to as
lymphomas of mucosa-associated lymphoid
tissue (MALT), or MALTomas.

 Carcinoid tumors arise from neuroendocrine
organs (e.g., the endocrine pancreas) and
neuroendocrine-differentiated
gastrointestinal epithelia (e.g., G-cells)

 Gastric carcinoids may be associated with
endocrine cell hyperplasia, chronic atrophic
gastritis, and Zollinger-Ellison syndrome

 These tumors were called “carcinoid”
because they are slower growing than
carcinomas.
 WHO classification describes these as low- or
intermediate grade neuroendocrine tumors.
 The grade is based on mitotic activity and
the fraction of cells immunohistochemcially
positive for Ki67, a mitotic marker.
 High-grade neuroendocrine tumors, termed
neuroendocrine carcinoma, frequently
display necrosis and, in the GI tract, are
most common in the jejunum

 Carcinoid tumors are intramural or
submucosal masses that create small
polypoid lesions .
 The tumors are yellow or tan in appearance
and elicit an intense desmoplastic reaction
that may cause kinking of the bowel and
obstruction.
 On histologic examination, carcinoid tumors
are composed of islands, trabeculae, strands,
glands, or sheets of uniform cells with scant,
pink granular cytoplasm and a round to oval
stippled nucleus

 The peak incidence of carcinoid tumors is in
the sixth decade, but they may appear at
any age.
 Symptoms are determined by the hormones
produced.
 carcinoid syndrome is caused by vasoactive
substances secreted by the tumor that cause
cutaneous flushing, sweating, bronchospasm,
colicky abdominal pain, diarrhea, and right-
sided cardiac valvular fibrosis.

 carcinoid syndrome occurs in less than 10% of
patients and is strongly associated with
metastatic disease due to first pass effect of
liver.

 The most important prognostic factor for
gastrointestinal carcinoid tumors is location:

 Foregut carcinoid tumors, those found
within the stomach, duodenum proximal to
the ligament of Treitz, and esophagus, rarely
metastasize and generally are cured by
resection.
 Rare, duodenal gastrin-producing carcinoid
tumors, gastrinomas, have been associated
with proton pump inhibitor therapy

 Midgut carcinoid tumors that arise in the
jejunum and ileum often are multiple and
tend to be aggressive.
 In these tumors, greater depth of local
invasion, increased size, and presence of
necrosis and mitosis are associated with poor
outcome.

 Hindgut carcinoids arising in the appendix
and colorectum typically are discovered
incidentally.
 Those in the appendix occur at any age and
are almost uniformly benign.
 Rectal carcinoid tumors tend to produce
polypeptide hormones and may manifest with
abdominal pain and weight loss; they only
occasionally metastasize.

 Gastrointestinal stromal tumor (GIST) is the
most common mesenchymal tumor of the
abdomen, and more than half of these
tumors occur in the stomach

 Overall, GISTs are slightly more common in
males. The peak incidence of gastric GIST is
around 60 years of age, with less than 10%
occurring in persons younger than 40 years of
age

 75% to 80% of all GISTs have oncogenic,
gain-of-function mutations of the gene
encoding the tyrosine kinase c-KIT, which
is the receptor for stem cell factor.
 Another 8% of GISTs have mutations that
activate a related tyrosine kinase, platelet-
derived growth factor receptor A (PDGFRA)

 GISTs appear to arise from, or share a
common stem cell with, the interstitial cells
of Cajal, which express c-KIT, are located in
the muscularis propria, and serve as
pacemaker cells for gut peristalsis

 Primary gastric GISTs usually form a solitary,
well circumscribed, fleshy, submucosal mass.
 Metastases may form multiple small serosal
nodules or fewer large nodules in the liver;
spread outside of the abdomen is uncommon.
 GISTs can be composed of thin, elongated
spindle cells or plumper epithelioid cells.
 The most useful diagnostic marker is c-KIT,
consistent with the relationship between
GISTs and interstitial cells of Cajal, which is
immunohistochemically detectable in 95% of
these tumors

 Symptoms of GISTs at presentation may be
related to mass effects or mucosal
ulceration.
 Complete surgical resection is the primary
treatment for localized gastric GIST.
 The prognosis correlates with tumor size,
mitotic index, and location, with gastric
GISTs being somewhat less aggressive than
those arising in the small intestine.
 Recurrence or metastasis is rare for gastric
GISTs less than 5 cm across but common for
mitotically active tumors larger than 10 cm

 Most of the length of the gastrointestinal
tract
 Affect nutrient and water transport
 Site where the immune system interfaces
with a diverse array of antigens present in
food and gut microbes.
 Most common site of gastrointestinal
neoplasia

 Hernias, intestinal adhesions,
intussusception, and volvulus account for
80% of mechanical obstructions , while
tumors and infarction account for most of
the remainder

 Hirschsprung Disease
 Abdominal Hernia

 Weakness or defect in the wall of the
peritoneal cavity
 Serosa-lined pouch of peritoneum called a
hernia sac.
 Pressure at the neck of the pouch may impair
venous drainage, leading to stasis and
edema.
 Permanent entrapment, or incarceration,
and over time, arterial and venous
compromise, or strangulation, can result in
infarction

 Gastrointestinal tract is supplied by the
celiac, superior mesenteric, and inferior
mesenteric arteries.
 As they approach the intestinal wall, the
superior and inferior mesenteric arteries fan
out to form the mesenteric arcades

 Small intestine and colon to tolerate slowly
progressive loss of the blood supply from one
artery

 Ischemic Bowel Disease
 Hemorrhoids

 Ischemic damage to the bowel wall
 Mucosal infarction, extending no deeper
than the muscularis mucosa;
 Transmural infarction involving all three
layers of the wall

 Mucosal or mural infarctions often are
secondary to acute or chronic hypoperfusion
 Transmural infarction is generally caused by
acute vascular obstruction.

 Important causes- severe atherosclerosis
(which is often prominent at the origin of
mesenteric vessels), aortic aneurysm,
hypercoagulable states, oral contraceptive
use, and embolization of cardiac vegetations
or aortic atheromas
 Intestinal hypoperfusion associated with
cardiac failure, shock, dehydration, or
vasoconstrictive drugs.

 Systemic vasculitides mesenteric venous
thrombosis can also lead to ischemic disease,
but is uncommon.
 Other causes include invasive neoplasms,
cirrhosis, portal hypertension, trauma, or
abdominal masses that compress the portal
drainage.

 PATHOGENESIS ‘
 ischemia occur in two phases
 Initial hypoxic injury occurs at the onset of
vascular compromise and, although some
damage occurs, intestinal epithelial cells are
relatively resistant to transient hypoxia
 Second phase, reperfusion injury, is
initiated by restoration of the blood supply
and associated with the greatest damage

 The severity of vascular compromise,
 Time frame during which it develops, and
 Vessels affected are the major variables
that determine severity of ischemic bowel
disease

 Intestinal segments at the end of their
respective arterial supplies are particularly
susceptible to ischemia
 watershed zones include the splenic
flexure, where the superior and inferior
mesenteric arterial circulations terminate,
and, to a lesser extent, the sigmoid colon
and rectum where inferior mesenteric,
pudendal, and iliac arterial circulations end

 Intestinal capillaries run alongside the
glands, from crypt to surface, before making
a hairpin turn at the surface to empty into
the postcapillary venules.
 This anatomy protects the crypts, which
contain the epithelial stem cells that are
necessary to repopulate the surface

 Mucosal and mural infarction may involve
any level of the gut from stomach to anus
 Segmental and patchy in distribution
 Mucosa is hemorrhagic and often ulcerated
 Bowel wall is thickened by edema
 With severe disease, extensive mucosal and
submucosal hemorrhage and necrosis, but
serosal hemorrhage and serositis generally
are absent

 Blood-tinged mucus or blood accumulates
within the lumen.
 Coagulative necrosis of the muscularis
propria occurs within 1 to 4 days and may be
associated with purulent serositis and
perforation

 In mesenteric venous thrombosis, arterial
blood continues to flow for a time, resulting
in a less abrupt transition from affected to
normal bowel.
 Propagation of the thrombus may lead to
secondary involvement of the splanchnic bed
and hence acute arterial obstruction.

 Microscopic examination
 Atrophy or sloughing of surface epithelium
 Crypts may be hyperproliferative.
 Neutrophils are recruited within hours of
reperfusion
 Chronic ischemia is accompanied by fibrous
scarring of the lamina propria
 Bacterial superinfection and enterotoxin
release may induce pseudomembrane

 Clinical Features
 Older persons with coexisting cardiac or
vascular disease.
 Sudden, severe abdominal pain and
tenderness, sometimes accompanied by
nausea, vomiting, bloody diarrhea, or grossly
melanotic stool
 Shock and vascular collapse within hours as a
result of blood loss.

 Peristaltic sounds diminish or disappear,
 Muscular spasm creates boardlike rigidity of
the abdominal wall
 The diagnosis of intestinal infarction may be
delayed or missed, with disastrous
consequences.
 Mucosal barrier breaks down, bacteria enter
the circulation and sepsis can develop;

 The overall progression of ischemic enteritis
depends on the underlying cause and severity
of injury
 Mucosal and mural infarctions may progress
to more extensive transmural infarction if
the vascular supply is not restored by
correction of the insult.
 Chronic ischemia may masquerade as
inflammatory bowel disease

 CMV infection can be a complication of
immunosuppressive therapy
 Radiation enterocolitis occurs when the
gastrointestinal tract is irradiated.
 In addition to epithelial damage, radiation-
induced vascular injury may be significant
and produce changes that are similar to
ischemic disease.
 In addition to clinical history, the presence of
bizarre “radiation fibroblasts” within the
stroma may provide an important clue to the
etiology

 Necrotizing enterocolitis is an acute disorder
of the small and large intestines that can
result in transmural necrosis
 Most common acquired gastrointestinal
emergency of neonates, particularly those
who are premature or of low birth weight,
and occurs most often when oral feeding is
initiated

 Angiodysplasia is characterized by
malformed submucosal and mucosal blood
vessels. It occurs most often in the cecum or
right colon, and usually presents after the
sixth decade of life .

 5% of the general population
 Dilated anal and perianal collateral vessels
that connect the portal and caval venous
systems to relieve elevated venous pressure
within the hemorrhoid plexus.

 Factors that predispose to hemorrhoids are
constipation and associated straining, which
increase intra-abdominal and venous
pressures, venous stasis of pregnancy, and
portal hypertension.

 External hemorrhoids Collateral vessels
within the inferior hemorrhoidal plexus are
located below the anorectal line
 Internal hemorrhoids dilation of the
superior hemorrhoidal plexus within the
distal rectum

 On histologic examination, hemorrhoids
consist of thin-walled, dilated submucosal
vessels that protrude beneath the anal or
rectal mucosa.

 Clinical Features
 Hemorrhoids often manifest with pain and
rectal bleeding, particularly bright red blood
seen on toilet tissue.
 Except in pregnant women, hemorrhoids are
rarely encountered in persons younger than
30 years

 Malabsorptive Diarrhea
 Infectious Enterocolitis

 Cystic Fibrosis
 Celiac Disease
 Environmental (Tropical) Enteropathy
 Lactase (Disaccharidase) Deficiency
 Abetalipoproteinemia
 Irritable Bowel Syndrome
 Microscopic Colitis
 Graft-Versus-Host Disease

 Defective absorption of fats, fat- and water-
soluble vitamins, proteins, carbohydrates,
electrolytes and minerals, and water.
 Chronic malabsorption causes weight loss,
anorexia, abdominal distention, borborygmi,
and muscle wasting.
 Hallmark of malabsorption is steatorrhea,
characterized by excessive fecal fat and
bulky, frothy, greasy, yellow or clay-colored
stools

 Diarrhea is defined as an increase in stool
mass, frequency, or fluidity, typically to
volumes greater than 200 mL per day
 Painful, bloody, small-volume diarrhea is
known as dysentery
 Secretory diarrhea is characterized by
isotonic stool and persists during fasting.
 Osmotic diarrhea, is due to osmotic forces
exerted by unabsorbed luminal solutes

 Malabsorptive diarrhea caused by
inadequate nutrient absorption is associated
with steatorrhea and is relieved by fasting
 Exudative diarrhea is due to inflammatory
disease and characterized by purulent,
bloody stools that continue during fasting

 Disturbance in at least one of the four phases
of nutrient absorption:
 Intraluminal digestion,
 Terminal digestion
 Transepithelial transport
 Lymphatic transport

 Diarrhea, abdominal pain, urgency, perianal
discomfort, incontinence, and hemorrhage.

 Comma-shaped, gram negative bacteria that
cause cholera
 Endemic in the Ganges Valley of India and
Bangladesh
 Marked seasonal variation in most climates
due to rapid growth of Vibrio bacteria at
warm temperatures
 Only animal reservoirs are shellfish and
plankton
 Few V. cholerae serotypes are pathogenic,

 Noninvasive and remain within the intestinal
lumen
 Flagellar proteins, which are involved in
motility and attachment, are necessary for
efficient bacterial colonization,
 and a secreted metalloproteinase that also
has hemagglutinin activity is important for
bacterial detachment and shedding in the
stool.

 the preformed enterotoxin, cholera toxin,
which causes disease
 There are five B subunits that direct
endocytosis and a single active A subunit
 A subunit is transported from the
endoplasmic reticulum lumen into the
cytosol, where it interacts with cytosolic ADP
ribosylation factors to ribosylate and activate
the G protein Gsα

 This stimulates adenylate cyclase and the
resulting increases in intracellular cyclic
adenosine monophosphate (cAMP) open the
cystic fibrosis transmembrane conductance
regulator (CFTR), which releases chloride ions
into the lumen.
 Sodium and bicarbonate absorption are also
reduced.
 Accumulation of these ions creates an osmotic
gradient that draws water into the lumen,
leading to massive secretory diarrhea.
 Remarkably, mucosal biopsy specimens show
only minimal morphologic alterations

 Campylobacter jejuni is the most common
bacterial enteric pathogen in developed
countries and is an important cause of
traveler’s diarrhea
 Ingestion of improperly cooked chicken, but
outbreaks also can be caused by
unpasteurized milk or contaminated water.

 Flagella allow Campylobacter to be motile.
 This facilitates adherence and colonization,
which are also necessary for mucosal
invasion.
 Cytotoxins that cause epithelial damage and
a cholera toxin–like enterotoxin are also
released by some C. Jejuni isolates.
 Campylobacter infection can result in
reactive arthritis, primarily in patients with
HLA-B27.

 Specific diagnosis is primarily by stool
culture

 Watery diarrhea, either acute or with onset
after an influenza-like prodrome, is the
primary manifestation, and dysentery
develops in 15% to 50% of patients.

 gram-negative bacilli that are
unencapsulated, non-motile, facultative
anaerobes.

 Shigella organisms are resistant to the harsh acidic
environment of the stomach.
 Once in the intestine, organisms are taken up by M
epithelial cells, which are specialized for sampling
and uptake of luminal antigens.
 After intracellular proliferation, the bacteria escape
into the lamina propria.
 These bacteria then infect small intestinal and
colonic epithelial cells through the basolateral
membranes, which express bacterial receptors.
 Alternatively, luminal shigellae can directly modulate
epithelial tight junctions to expose basolateral
bacterial receptors. Some Shigella dysenteriae
serotypes also release the Shiga toxin Stx, which
inhibits eukaryotic protein synthesis and causes host
cell death.

 Shigella infections are most prominent in
the left colon, but the ileum may also be
involved, perhaps reflecting the abundance
of M cells in the epithelium overlying the
Peyer’s patches.


 The histologic appearance in early cases is
similar to that in other acute self-limited
colitides

 Complications of Shigella infection are
uncommon and include reactive arthritis, a
triad of sterile arthritis, urethritis, and
conjunctivitis that preferentially affects HLA-
B27– positive men between 20 and 40 years
of age.
 Hemolytic uremic syndrome, which typically
is associated with enterohemorrhagic
Escherichia coli (EHEC), also may occur after
infection with shigellae that secrete Shiga
toxin.

 Escherichia coli are gram-negative bacilli
that colonize the healthy GI tract; most are
non-pathogenic, but a subset cause human
disease.

 Enterohemorrhagic E. coli (EHEC)
organisms are categorized as O157:H7 and
non-O157:H7 serotypes.
 Outbreaks of E. coli O157:H7 in developed
countries have been associated with the
consumption of inadequately cooked ground
beef, milk, and vegetables.
 Both O157:H7 and non-O157:H7 serotypes
produce Shiga-like toxins and can cause
dysentery.
 They can also give rise to hemolytic-uremic
syndrome

 Enterotoxigenic E. coli (ETEC) organisms
are the principal cause of traveller's
diarrhea, and are spread by the faecal-oral
route.

 They express a heat labile toxin (LT) that is
similar to cholera toxin and a heat-stable
toxin (ST) that increases intracellular cGMP
with effects similar to the cAMP elevations
caused by LT

 Enteroinvasive E. coli (EIEC) organisms
resemble Shigella bacteriologically but do
not produce toxins.
 They invade the gut epithelial cells and
produce a bloody diarrhea.

 Enteroaggregative E. coli (EAEC) organisms
attach to enterocytes by adherence
fimbriae.


 Although they produce LT and Shiga-like
toxins, histologic damage is minimal

 members of the Enterobacteriaceae family of
gram-negative bacilli
 Salmonella typhi, the causative agent of
typhoid fever and nontyphoid Salmonella
strains that cause gastroenteritis.
 Nontyphoid Salmonella infection usually is
due to Salmonella enteritidis
 Infection is most common in young children
and elderly persons, with peak incidence in
summer and fall

 virulence genes encode a type III secretion
system capable of transferring bacterial
proteins into M cells and enterocytes----
activate host cell Rho GTP ases------
triggering actin rearrangement and bacterial
uptake into phagosomes where the bacteria
can grow.
 A molecule that induces epithelial release of
a chemo attractant eicosanoid that draws
neutrophils into the lumen and potentiates
mucosal damage

 Like S. enteritidis, S. typhi and S. Para typhi
are taken up by M cells and then engulfed by
mononuclear cells in the underlying lymphoid
tissue.
 Thus, infection causes Peyer’s patches in the
terminal ileum to enlarge into plateau-like
elevations up to 8 cm in diameter.
 Mucosal shedding creates oval ulcers
oriented along the long axis of the ileum.
 However, unlike S. enteritidis, S. typhi and
S. paratyphi can disseminate via lymphatic
and blood vessels

 Randomly scattered small foci of
parenchymal necrosis with macrophage
aggregates, termed typhoid nodules, are also
present in the liver, bone marrow, and lymph
nodes

 Campylobacter, Shigella, Salmonella, and many
other bacterial infections, including Yersinia and E.
coli, all induce a similar histopathology, termed
acute self-limited colitis, and these pathogens
cannot be reliably distinguished by tissue biopsy.
 Thus, specific diagnosis is primarily by stool culture.
 The histology of acute self-limited colitis includes
prominent lamina propria and intraepithelial
neutrophil infiltrates cryptitis (neutrophil
infiltration of the crypts) and crypt abscesses
(crypts with accumulations of luminal neutrophils)
also may be present.
 The preservation of crypt architecture in most cases
of acute self-limited colitis is helpful in distinguishing
these infections from inflammatory bowel disease

 Caused by Clostridium difficile, is also
known as antibiotic-associated colitis or
antibiotic-associated diarrhea.
 Disruption of the normal colonic microbiota
by antibiotics allows C. difficile overgrowth.
 Toxins released by C. difficile cause the
ribosylation of small GTPases, such as Rho,
and lead to disruption of the epithelial
cytoskeleton, tight junction barrier loss,
cytokine release, and apoptosis.

 Norovirus Norovirus, previously known as
Norwalk-like virus
 Rotavirus--Children between 6 and 24months
-- selectively infects and destroys mature
(absorptive) enterocytes in the small
intestine, and the villus surface is
repopulated by immature secretory cells.
This change in functional capacity results in
loss of absorptive function and net secretion
of water and electrolytes that is
compounded by an osmotic diarrhea from
incompletely absorbed nutrients.

Parasitic Disease---
 Ascaris lumbricoides,-traverses lung
 Strongyloides(autoinfection) –travesrses lung
 Necator americanus-- traverses lung
 Ancylostoma duodenale -- traverses lung
 Giardia lamblia(lactase deficiency)

 Multivisceral chronic disease
 Malabsorption
diarrhoea,lymphadenopathy,arthritis of
undefined origin
 Foamy macrophage having argyrophilic rods
 Gram positive actinomycetes..Tropheryma
whippelli
ACCUMULATE IN LAMINA PROPRIA AND
MESENTRIC LYMPHNODES CAUSING
LYMPHATIC OBSTRUCTION
 PAS POSITIVE DIASTASE RESISTANT GRANULES
IN LYSOSOMES

 Chronic relapsing abdominal pain,bloating
and changes in bowel habits
 Syndrome with multiple illnesses
 Rome criteria
 Pathogenesis unknown
 Psychosocial,diet,gut factors
 Constipation predominant,diarrhoea
predominant
 Bile acid malabsorption
 20 to 40years age/female
 3days per month for over 3 months

 acquired pseudodiverticular outpouchings of
the colonic mucosa and submucosa.
 rare in persons younger than 30 years of age,
but the prevalence approaches 50% in
Western adult populations beyond the age of
60
 under conditions of elevated intraluminal
pressure in the sigmoid colon

 the unique structure of the colonic
muscularis propria, where nerves, arterial
vasa recta, and their connective tissue
sheaths penetrate the inner circular muscle
coat to create discontinuities in the muscle
wall
 in the colon, external longitudinal muscle
layer is discontinuous, being gathered into
the three bands termed taeniae coli.

 small, flask-like outpouchings, usually 0.5 to
1 cm in diameter, that occur in a regular
distribution in between the taeniae coli
 Obstruction of diverticula leads to
inflammatory changes, producing
diverticulitis and peridiverticulitis.

 Most persons asymptomatic
 intermittent cramping, continuous lower
abdominal discomfort, constipation, and
diarrhea.
 most often resolves spontaneously or after
antibiotic treatment

 chronic condition resulting from
inappropriate mucosal immune activation.
 two major entities, Crohn disease and
ulcerative colitis

CROHN’S ULCERATIVE COLITIS
Ileum ± colon Colon only
Skip lesions Diffuse
Transmural inflammation Limited to mucosa and
submucosa
Toxic megacolon + Toxic megacolon -
Ulcers Deep, knifelike Superficial, broad-based
Stricture Yes Stricture rare

 more common in females and frequently
present during adolescence or in young
adults.

 The cause(s) of IBD remains uncertain
 a combination of errant host interactions
with intestinal microbiota, intestinal
epithelial dysfunction, and aberrant
mucosal immune responses.
 Genetics
 Mucosal immune responses
 Epithelial defects
 Microbiota

 Molecular linkage analyses of affected
families have identified NOD2 (nucleotide
oligomerization binding domain 2) ATG16L1,
and IRGM, as a susceptibility gene in Crohn
disease

 it is likely that some combination of
derangements that activate mucosal
immunity and suppress immunoregulation
contribute to the development of both
ulcerative colitis and Crohn disease
 TH17 T cells With polymorphisms of the IL-23
receptor confer protection from Crohn
disease and ulcerative colitis (IL-23 is
involved in the development and
maintenance of TH17 cells).

 in ulcerative colitis includes a significant TH2
component.
 However, the pathogenic role of TH2 cells in
IBD pathogenesis remains controversial.

 defects in intestinal epithelial tight junction
barrier function are present in patients with
Crohn disease and a subset of their healthy
first-degree relatives.

 Despite a growing body of data that suggest
that intestinal microbiota contribute to IBD
pathogenesis, their precise role remains to
be defined.
 In keeping with this, some antibiotics, such
as metronidazole, can be helpful in
maintenance of remission in Crohn disease

 terminal ileum, ileocecal valve, and
cecum.
 Disease is limited to the small intestine
alone in about 40% of cases; the small
intestine and the colon both are involved in
30% of patients; and the remainder of cases
are characterized by colonic involvement
only.
 The presence of multiple, separate, sharply
delineated areas of disease, resulting in skip
lesions, is characteristic of Crohn disease
 Strictures are common

 The microscopic features of active Crohn
disease include abundant neutrophils that
infiltrate and damage crypt epithelium.
 Clusters of neutrophils within a crypt are
referred to as a crypt abscess and often are
associated with crypt destruction.
 Ulceration is common in Crohn disease, and
there may be an abrupt transition between
ulcerated and normal mucosa.
 Repeated cycles of crypt destruction and
regeneration lead to distortion of mucosal
architecture.

 In most patients, disease begins with
intermittent attacks of relatively mild
diarrhea, fever, and abdominal pain.
 Right lower quadrant pain, fever, and bloody
diarrhea that may mimic acute appendicitis
or bowel perforation.
 Periods of active disease typically are
interrupted by asymptomatic intervals that
last for weeks to many months

 Extraintestinal manifestations of Crohn
disease include uveitis, migratory
polyarthritis, sacroiliitis, ankylosing
spondylitis, erythema nodosum, and clubbing
of the fingertips, any of which may develop
before intestinal disease is recognized

 involved colonic mucosa may be slightly red and
granular-appearing or exhibit extensive broad-
based ulcers.
 The transition between diseased and
uninvolved colon can be abrupt.
 Ulcers are aligned along the long axis of the
colon but typically do not replicate the
serpentine ulcers of Crohn disease.
 Isolated islands of regenerating mucosa often
bulge into the lumen to create small elevations,
termed pseudopolyps.
 Chronic disease may lead to mucosal atrophy
and a flat, smooth mucosal surface lacking
normal folds.

 mural thickening is absent, the serosal
surface is normal, and strictures do not
occur.
 Inflammation and inflammatory mediators
can damage the muscularis propria and
disturb neuromuscular function leading
tocolonic dilation and toxic megacolon,
which carries a significant risk of
perforation.

 Histologic features of mucosal disease in
ulcerative colitis are similar to those in
colonic Crohn disease and include
inflammatory infiltrates, crypt abscesses,
crypt distortion, and epithelial metaplasia.
However, skip lesions are absent and
inflammation generally is limited to the
mucosa and superficial submucosa

 Ulcerative colitis is a relapsing disorder
characterized by attacks of bloody diarrhea
with expulsion of stringy, mucoid material
and lower abdominal pain and cramps that
are temporarily relieved by defecation.

 One of the most feared long-term
complications of ulcerative colitis and
colonic Crohn disease is the development of
neoplasia.
 This process begins as dysplasia, which, just
as in Barrett esophagus and chronic gastritis,
is a step along the road to full-blown
carcinoma.
 Risk increases sharply 8 to 10 years after
disease initiation.
 Patients with pancolitis are at greater risk
than those with only left-sided disease.

 common in the colon but may occur in the
esophagus, stomach, or small intestine
 Without stalks are referred to as sessile.
 stalks are termed pedunculated
 classified as nonneoplastic or neoplastic.

 inflammatory,
 hamartomatous, or
 hyperplastic.

 clinical triad of rectal bleeding,
 mucus discharge, and
 an inflammatory lesion of the anterior rectal
wall.
 cause is impaired relaxation of the anorectal
sphincter, creating a sharp angle at the
anterior rectal shelf
 recurrent abrasion and ulceration of the
overlying rectal mucosa

 sporadically and
 as components of various genetically
determined or acquired syndromes
 disorganized, tumor-like growths composed
of mature cell types normally present at the
site at which the polyp develops
 Juvenile Polyps
 Peutz-Jeghers Syndrome

 the most common type of hamartomatous
polyp
 sporadic or syndromic
 children younger than 5 years of age.
 located in the rectum,
 Sporadic juvenile polyps are usually solitary
but in persons with the autosomal dominant
syndrome of juvenile polyposis the number
varies from 3 to as many as 100
 juvenile polyposis syndrome is associated
with increased risk for the development of
colonic adenocarcinoma.

 pedunculated, smooth surfaced, reddish
lesions that are less than 3 cm in diameter
and display characteristic cystic spaces on
cut sections.
 Microscopic examination shows the spaces to
be dilated glands filled with mucin and
inflammatory debris

 rare autosomal dominant disorder
 multiple gastrointestinal hamartomatous polyps
and mucocutaneous hyperpigmentation that
carries an increased risk of several malignancies,
including cancers of the colon, pancreas,
breast,lung, ovaries, uterus, and testes, as well
as other unusual neoplasms
 Histologic examination demonstrates a
characteristic arborizing network of connective
tissue,smooth muscle, lamina propria, and
glands lined by normal-appearing intestinal
epithelium

 epithelial proliferations that typically are
discovered in the sixth and seventh decades
of life.
 decreased epithelial cell turnover and
delayed shedding of surface epithelial cells
 Left colon and typically are less than 5 mm
in diameter.
 singly but more frequently are multiple,
 hyperplastic polyps are composed of mature
goblet and absorptive cells.

 Adenomas
 Familial syndromes ---FAP(Familial
Adenomatous Polyposis) /HNPCC
 Adenocarcinoma

 colonic adenomas,benign polyps that give
rise to a majority of colorectal
adenocarcinomas.
 Colorectal adenomas are characterized by
the presence of epithelial dysplasia
 adenomas range from 0.3 to 10 cm in
diameter and can be pedunculated or
sessile,
 the cytologic hallmark of epithelial dysplasia
is nuclear hyperchromasia, elongation, and
stratification .

 the epithelium fails to mature as cells
migrate out of the crypt
 classified as tubular, tubulovillous, or
villous on the basis of their architecture
 The histologic features of sessile serrated
adenomas overlap with those of hyperplastic
polyps and the typical cytologic features of
dysplasia are lacking

 Size is the most important characteristic
that correlates with risk of malignancy. ,
 In addition to size, high-grade dysplasia is a
risk factor for cancer in an individual polyp

 Familial Adenomatous Polyps-an autosomal
dominant disorder marked by the appearance
of numerous colorectal adenomas by the
teenage years. It is caused by mutations of
the adenomatous polyposis coli gene (APC).A
count of at least 100 polyps is necessary for
a diagnosis of classic FAP, and as many as
several thousand may be present. Colorectal
adenocarcinoma develops in 100% of patients
with untreated FAP, often before age 30.

 Specific APC mutations are also associated
with the development of other
manifestations of FAP and explain variants
such as Gardner syndrome(with
osteomas,desmoid,thyroid and dental
tumors) Turcot syndrome(CNS tumors,
medulloblastoma 67%,glioblastoma 33%).

 Hereditary Nonpolyposis Colorectal Cancer-
Lynch syndrome, originally was described as
familial clustering of cancers at several sites
including the colorectum, endometrium,
stomach, ovary, ureters, brain, small bowel,
hepatobiliary tract, and skin. HNPCC is
caused by inherited germline mutations in
genes that encode proteins responsible for
the detection, excision, and repair of errors
that occur during DNA replication. At least
five such mismatch repair genes have been
recognized, but a majority of HNPCC cases
involve either MSH2 or MLH1.

 the most common malignancy of the
gastrointestinal tract
 Colorectal cancer incidence peaks at 60 to 70
years of age, and less than 20% of cases
occur before age 50. Males are affected
slightly more often than females
 The combination of molecular events that
lead to colonic adenocarcinoma is
heterogeneous and includes genetic and
epigenetic abnormalities. At least two
distinct genetic pathways APC/β-catenin
pathway, have been described.

 APC is a key negative regulator of β-
catenin, a component of the WNT signaling
pathway. The APC protein normally binds to
and promotes degradation of β-catenin. With
loss of APC function, β-catenin accumulates
and translocates to the nucleus, where it
activates the transcription of genes, such as
those encoding MYC and cyclin D1, which
promote proliferation

 Both copies of the APC gene must be
functionally inactivated, either by mutation
or epigenetic events, for adenomas to
develop

 Tumors in the proximal colon often grow as
polypoid, exophytic masses that extend
along one wall of the large-calibercecum
and ascending colon; these tumors rarely
causeobstruction. By contrast, carcinomas in
the distal colontend to be annular lesions
that produce “napkin ring” constrictions
and luminal narrowing

 composed of tall columnar cells that resemble
dysplastic epithelium found in adenomas. The
invasive component of these tumors elicits a
strong stromal desmoplastic response, which is
responsible for their characteristic firm
consistency.
 Some poorly differentiated tumors form few
glands.
 Others may produce abundant mucin that
accumulates within the intestinal wall, and
these carry a poor prognosis.
 Tumors also may be composed of signet ring cells
that are similar to those in gastric cancer

 Symptoms -fatigue and weakness due to iron
deficiency anemia. Left-sided colorectal
adenocarcinomas may produce occult
bleeding, changes in bowel habits, or
cramping left lower quadrant discomfort.
 Staging -TNM
 Prognosis-the two most important prognostic
factors are depth of invasion and the
presence or absence of lymph node
metastases.

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