7-8 git pdf - dr nadia

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

Congenital anomalies
1- Atresia and stenosis

 Congenital intestinal obstruction

-Complete: Atresia

-Incomplete: Stenosis

 Duodenal: most common

-Jejunum and ileum: equal

-Rectum: rare

 Developmental failure

 intrauterine vascular accidents, or

intussuception

 Imperforate anus

2- Meckel’s Diverticulum

 Persistence of omphalomesenteric duct (vitelline duct) (on anti-

mesenteric side)

 True : all layers.

 Disease of 2’s

-2% of population (mostly asymptomatic)

- 2:1, M:F

-2 inch in length

-2 ft of ileocecal valve

-2 types of ectopic tissue in 1/2 of cases (gastric and pancreatic)

-2 major complications (pain with inflammation; hemorrhage with ulcer)

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

3- Congenital Aganglionic Megacolon “Hirschsprung Disease”

 Absence of ganglia (failure of migration of the neural crest cells and

arrest at some points before reaching the anus).

 Loss of both submucosal (Meissner) and myenteric (Auerbach) in a

segment and loss of neural coordination and functional obstruction.

 M:F 4:1. and can be in sporadic or familial cases.

 1 in 5000 to 8000.

 Down syndrome (10% of HD) and (5%) serious neurologic abnormalities.

 Genetic defects:

 Endothelin 3

 GCDGF

 Receptor tyrosine kinase.

 Acquired in Chagas disease (typanosomiasis), neoplastic obstruction,

toxic megacolon, and functional.

Clinical features

 Presents in neonatal period (failure to pass meconium; abdominal

distention)

 Risk of perforation, sepsis, enterocolitis, fluid disturbances and rupture

in advanced cases.

 Alternating obstruction and diarrhea

 The rectum is always affected, with variable involvement of proximal

segments,

 Aganglionic segment causes functional obstruction with distention

proximal to aganglionic segment, which may be massive reach to 15-20
cm in diameter.

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

Vascular diseases:
a. Ischemic bowel disease
b. Angiodysplasia
c. Hemorrhoids

a. Ischemic bowel disease:

 Acute obstruction of one artery may lead to infarction of mm. 50-75%

death rate.

 Old individuals, pain and tenderness, bloody diarrhea, rigid abdomen

and paralytic ileus.

 Insidious loss has no effect (anastomosis), and present with chronic

ischemic colitis, with episodes of bloody diarrhea.

 Transmural infarction result from mechanical obstruction of major

artery.

 Mucosal or mural infarction more often results from hypoperfusion

(acute or chronic).

The predisposing conditions of ischemia are:

 1- arterial thrombosis: in severe atherosclerosis, at origin of aa. Or

arteritis, surgical accidents, dissecting aneurysm, hypercoagulable
state.

 2- arterial embolism.

 3- venous thrombosis.

 4- Non occlusive ischemia HF, shock, dehydration, drugs.

 5- Miscellaneous as radiation, volvulus, stricture or hernia.

 Embolus: superior mesenteric artery branches, source: embolus of

heart (mural thrombus, valvular vegetation)

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

b. Angiodysplasia

 -tortuous dilatation of the veins in the submucosal and mucosal blood

vessels with ectasia of veins.

 Prone to rupture, and presents with massive GIT-bleeding (20% of

significant massive lower GIT bleeding),

 Prevalence:<1%

 Sixth decade, pathogenesis, mechanical, with vascular degenerative

changes in aging.

 Osler-Weber-Rendu syndrome (hereditary hemorrhagic telangiectasia)

Hemorrhoids

 dilated veins of hemorrhoidal plexus

 -Internal
 -External
 -(BPR or streaks on stool), thrombosis, pain

 5% of population
 elevated venous pressure

 constipation
 straining venous stasis of pregnancy

 collateral channels in portal HTN
 rare under 30 except in pregnant women

Enterocolitis

 Infectious

 Necrotizing

 Pseudomembranous

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

 Infectious

 -Viral (Rotavirus)

 -Bacterial

 E. coli; Shigella; V. Cholerae; C. difficile

 -Parasites and protozoa (nematodes; flatworms; protozoa -Giardia

lambdia; E. histolytica)

Diarrhea

Secretory Diarrhea

more than 500 ml per day fluid which is isotonic with

plasma and persist in fasting.

Osmotic diarrhea

output more than 500 ml per day osmotic forces by

luminal solutes that abate on fasting.

Exudative diarrhea

(WBC & RBC in stool) that persist in fasting.

Malabsorptive:
long term weight loss, voluminous bulky stools with increased osmolarity of
it due to unabsorbed nutrients, and excess fat.

Salmonella enteritidis:

Milk, beef, eggs, poultry ,Self limiting diarrhea, dysentery pain, bacteremia.

Shigella:

Person-to-person. Milk, poultry,Produce mucosal ulcer ,Fever, pain, Exudative
diarrhea ,dysentery, epidemic spread

Vibrio cholera:

Water borne,Watery diarrhea, cholera, pandemic spread

Giardiasis

Morphology, clinical features: malabsorptive diarrhea.

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

Staphylococcus aureus:

Milk product and fatty food.

Acute explosive Exudative diarrhea.

Clostridium difficile :

Following antibiotic use, nosocomial acquisition Fever,

pain,

bloody

diarrhea,

Campylobacter :

Milk, poultry, animal (dog) contact.

Fever, pain, Secretory Diarrhea, dysentery

Clostridium perfringens: Produce gas gangrene

Others

 Necrotizing enterocolitis

 Acute, necrotizing inflammation of small and/or large intestines

 Most common acquired GI emergency in premature or low birth weight

neonate

 Mild GI symptoms or fulminant illness

Tuberculous
infection→

Transverse ulcer and Caseating granuloma

Pseudomembranous
colitis→

C. difficile.,
Gross and Micro: pseudomemnrane

Amebiasis→
Bloody

exudative

diarrhea

Flask shaped ulcer, complications: liver
abscess

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

 Multifactorial - immaturity of the gut’s immune system

 Release of cytokines and endotoxins damages mucosa and blood supply

 Edema to necrosis to gangrenous bowel



Terminal ileum or ascending colon

Morphology

NEC  typically  involve  the  terminal  ileum,
cecum,  &  right  colon.  The  involved
segment  is  .Distended,  friable,  and
congested,  or  it  can  be  gangrenous.
Peroration with peritonitis is May be seen.

Necrotizing enterocolitis, mucosal surface (and
comparison  with  normal)  .The  bowel  is
distended,  congested,  and  often  frankly
necrotic.  (Compare  the  involved  segment  of
ntestine  below  with  the  more  normal  segment
above.)

Compared to normal bowel at the left,
bowel involved by NEC at the right shows
hemorrhagic

coagulative

necrosis,

beginning in the mucosa and extending to
involve the muscular wall, with the potential
for perforation.

Pneumatosis

intestinalis,

necrotizing

enterocolitis .Pneumatosis intestinalis, which
is present in many but not all cases, is
represented by submucosal or subserosal
gas-filled cysts.

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

 Transmural necrosis: when severe, the

necrosis may progressively involve all
layers of the bowel through to the serosa
(transmural).

 This type of involvement, which begins at

the luminal aspect of the bowel, is typical
of ischemic injury.

 The necrosis is accompanied by variable

amounts

inflammation

and

hemorrhage.

 Pseudomembranous colitis

(antibiotic associated)

 Yellow green false membrane (mixture of mucous and neutrophils)

 Toxin produced by Clostridium difficile (acquired nasocomially in 20% of

pxs in long term hospitalization)

 Antibiotics allow overgrowth of C. difficile

 Sudden onset of fever and diarrhea in a patient who is seriously ill or

post operative who is receiving antibiotics

 diarrhea, dehydration, shock death

 Exotoxin A and B

 binds to enteric receptors causing injury to actin filaments and

 cell retraction

Malabsorption

 Defect in the assimilation of food (digestion and absorption)

 Intraluminal stage

a. Secretory Phase (Chronic pancreatitis/insufficiency)

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

b. Biliary Phase (Biliary obstruction due to calculus or tumor)

 Intestinal Stage (terminal digestion)

a. Surface Phase (Celiac disease; bowel resection)

b. Cellular Phase (Disaccharidase deficiency)

 Removal Stage (transepithelial transport)

a. Delivery Phase (Whipple diease)

Celiac sprue

Etiology and pathogenesis:

 Gluten, gliadin protein in wheat, oat, barley, and rye

 hypersensitivity (immunologic) reaction to gluten

 90-95% - HLA DQ 2 or 8.

 Whites - rare in native Africans, Japanese, Chinese

 Gluten - malabsorption -gluten free - improvement

 Long term risk of malignancy -lymphoma (2X normal)

 Distinct from Tropical sprue

Infant

 Failure to thrive
 Apathy
 Pallor
 Anorexia
 Abdominal distention/pain
 Developmental Delay
 Muscle wasting
 Hypotonia
 Stools soft, bulky, malodorous, clay-colored

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

Child

 Anemia

 Rickets

 Low weight

 Small stature

 Irritability

Adult

 Diarrhea/ steatorrhea

 Weight loss

 Cheilosis / glossitis / Apthous ulcers

 Anemia

 Anorexia/nausea/vomiting

 Flatulence

 Lactose/sucrose intolerance

morphology

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

pathology

 Excess lymphocytes

 Hyperplastic crypts

 Flattened villi

 Hypoplasia

Blood tests

 Antigliadin IgG and IgA

 Endomysium IgA

 Tissue transglutaminase IgA by ELISA

 Total IgA

Tropical sprue

 Occur in people living or visiting the tropics. (Caribbean, central and

south Africa, India, south east Asia, central and south America).

 No specific cause.

 Characterized by bacterial overgrowth by enterotoxigenic organisms,

e.g. E.coli, Hemophilus.

 Morphology: variable, injury in cells, with increase in size of cells.

 Malabsorption after the infection.

 Treated by broad spectrum antibiotics.

Whipple disease

 Rare systemic disease, affecting intestine, CNS and joints.

 Gram positive rod shaped actinomycete: Tropheryma whippleli

 Engulfed by macrophages (PAS positive diastase resistant)

 Electron microscopy

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

 Seen in intestinal mucosa, mesenteric lymph nodes, joints and other

systemic areas.

 M:F 10:1, in fourth to fifth decade.

 Mala, polyathritis, obscure CNS complaints.

 Treated by antibiotics.

Bacterial overgrowth

 The proximal small bowel is inhabitated by bacteria as in colon (aerobic

and anaerobic).

 The small bowel is not sterile but the peristalsis prevents overgrowth,

which occur in:

 1- Luminal stasis: stricture, fistula, diverticula, blind loop or pouch,

reduplication, motility disorders, post-surgical.

 2- Hypochrlohydria or achlorhydria, by gastric mucosal atrophy or anti-

acid ingestion.

 3- Immune deficiency.

The etiology of malabsorption will be multi-factorial:

 1- bacterial deconjugation and dehydroxylation of luminal bile salts.

 2- mucosal damage by bacterial enzymes.

 3- bacterial inactivation of luminal lipase.

 4- competition of nutrients.

 Treated by appropriate antibiotics.

Disaccharidase deficiency

 congenital = rare.

 Acquired = common, by osmotic diarrhea.

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

 Bacterial fermentation of unabsorbed sugar will cause hydrogen

production = pH of stool will be decreased.

Abetalipoproteinemia:

Autosomal recessive disease= no lipoprotein B accumulation of triglyceride in
mucosal cells.

Idiopathic Inflammatory Bowel disease

 Inflammatory bowel disease (IBD) - single term to collectively refer to

either Crohn disease or ulcerative colitis

 Etiology unknown

 a. Genetic predisposition: HLA B27

 b. Abnormal host immunoreactivity

 C. infectious causes.

 d. structural changes.

 e. inflammation.

Inflammatory Bowel Disease

 Consists of two inflammatory disorders - Crohn’s disease (CD) and

ulcerative colitis (UC)

 Both are chronic, relapsing conditions of uncertain etiology

 Both have systemic, extraintestinal inflammatory manifestations

Crohn disease: Regional enteritis GROSS EXAMINATION

1. Chronic inflammation involving all layers (transmural) of the SI

 may occur at any point along the GI tract

 primarily involving SI and LI.

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

 40% SI Alone, 30% SI&LI, 30%colon alone. (may involve, duodenum,

stomach, esophagus and even mouth.

2. Mucosa shows linear ulceration and fistula

3. Segmental involvement/sparing

 Serosal creeping fat

 terminal ileitis as it was 1st described in 1930’s, regional ileitis,

granulomatous colitis.

4. Serosa is granular, dull and gray.

5. Wall is thick and rubbery.

6. Lumen is narrowed.

7.  Sharp  demarcation  of  diseased  bowel
segment  from  adjacent  un-involved
bowel  wall.  (when  multiple  segments
involved = skip lesions).

8. Cobble stone appearance.

9. Narrow fissures develop, penetrate
deeply cause bowel adhesion with fistula
formation, or sinus tract formation.

10. free perforation or localized abscess.

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

Crohn disease: microscopy:

 Inflammation (transmural) spread through the bowel wall to adjacent

mesenteric fat.

 Mucosal inflammation : neutrophils, and crypt abscess.

 Ulceration in severe active disease.

 Chronic mucosal damage (crypt distortion) with villous blunting in SI,

atrophic changes, and metapalsia.

 -characteristic non-caseating granulomas ( seen in half of cases, in all

tissue layers, and involved and un involved areas).

CLINCAL FEATURES:

 tends to occur in young

adults

 diarrhea, crampy abdominal

pain, fever

 complications:

1-fistula,

obstruction. 2- occult blood
loss,  Fe++  def  anemia.  3-
malabsorption,
malnutrition, weight loss. 4-
fistula  and  stricture.  5-  extra  intestinal  manifestations:  polyarthritis,
sacro ileitis, ankylosing  spondilitis, erythematic nodosum,  clubbing of
fingers, uveitis, amyloidosis, and increased incidence of cancer of SI and
colon in 5-6 fold increase in risk.

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

Ulcerative colitis

1. Inflammation primarily involving the mucosa of the colon.

2. Diffuse, continuous inflammation that begins in the rectum and progresses
proximally. Pancolitis in 20%, 10% of these have backwash ileitis, remaining
40-50% rectosigmoid.

3. Pseudopolyp formation.

4. With chronic disease, there is atrophy.

5. Serosa normal.

6. Bloody diarrhea, from ruptured vessels in inflamed mucosa

 Toxic megacolon - rare complication - prominent dilatation and septic

shock.

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

MICROSCOPY:

 Early phase: neutrophils accumulate within the depths of the crypts of

Leiberkuhn forming crypt abscesses.

 Fibrosis cause crypt distortion. Mucous cell depletion.

 Later phase: mucosa ulcerates and pseudo-polyps form

 Late phase: after many years, mucosa becomes dysplastic, increasing

risk of colon carcinoma

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

Clinical features:

 ATTACKS

BLOODY

DIARRHEA.

 days, weeks, months and then

subside.

 Recur after months, and then

subside.

 Could be only single attack.

 PROGNOSIS:

 60% mild disease.

 97% relapse within 10 years.

 30 % colectomy in first 3 years (uncontrollable disease).

 Rarely fulminant = fatal.

 RISK OF CANCER: dysplasia in multiple sites.

 High in patients with pancolitis for 10 years or more, (20-30 fold increase

risk).

 If 35 years, there is 30% cancer development.

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

Between Crohn and UC, this finding is more commonly seen in:

Non-neoplastic bowel diseases

a. Diverticular disease
b. Hernias
c. Adhesions
d. Intussusception
e. Volvulus

a-Diverticular disease:

 Diverticulosis and Diverticulitis

 Acquired herniation

 Most common in left colon; particularly sigmoid colon

 Acute or chronic inflammation may occur

 Perforation, peritonitis, fistula

 Acquired

 rare under 30

 western pop over 60 prevalence: 50%

 Transmural inflammation--
 Pseudopolyp---------------
 Granuloma-----------------
 Diffuse---------------------
 skip lesions----------------
 toxic Megacolon-----------
 creeping fat----------------

 Primary Sclerosing Cholangitis--

 fissures and fistulas-------
 Cancer----------------------
 at any point in GI tract---
 Rectum---------------------



Crohn



Crohn



Crohn



Crohn



both but more in UC



Crohn



both but more in UC



Crohn



Crohn



Crohn



Crohn



Crohn



both but more in UC



Crohn



both but more in UC



Crohn



GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

b- Hernias

 -Serosal lined out-pouching of peritoneum
 -Loop of intestines becomes trapped (incarcerated) within the hernia sac
 -Bowel compressed, twisted at the mouth of hernia, compromising

blood supply - infarction (strangulation)

c- Adhesions

 -string-like or band-like portions of scar tissue that form during healing

after surgery or peritonitis

 -may result in obstruction (kinking, compression)

d- Intussusception

 -caused by an in-folding or telescoping of one segment of bowel into the

adjacent distal segment

 Infants and children: spontaneous and reversible

 Adults: tumor is usually a lead point

e- Volvulus

 -obstruction due to rotation or twisting of a loop of bowel around its

mesenteric base of attachment

 Sigmoid - most common site (cecum next)

Inflammation

 1. Miscellaneous

-graft vs. host

-drug induced

-radiation enterocolitis

-neutropenic colitis

-diversion colitis

GASTROINTESTINAL TRACT lecture 7-8 . Pathology Small and Large Intestines (1)

 2. Acute appendicitis

-etiology: bacteria

-fecolith impairing circulation, causing ischemia, necrosis and bacterial
contamination

-acute abdomen -RLQ pain- McBurney’s point

-fever and leukocytosis

 3. Collagenous and lymphocytic colitis

 Etiology: unknown

 possibly auto-immune

 chronic watery diarrhea in middle aged and older women

 spectrum of disease ranging from increased intraepithelial lymphocytes to

the presence of collagen band under the surface epithelium.