Pathology of the Gastrointestinal Tract Part 1
Small and Large Intestines
Grace Guzman, [email protected]
The Department of PathologyUniversity of Illinois at Chicago
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
Persistence of omphalomesenteric duct (vitelline duct)
Disease of 2’s-2% of population (mostly
asymptomatic)-M:F 2:1-2” 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)
Meckel Diverticulum
Congenital Aganglionic Megacolon
“Hirschsprung Disease”
Absence of ganglia -submucosal (Meissner) -myenteric (Auerbach)
Alternating obstruction and diarrhea
Aganglionic segment causes functional obstruction with distention proximal to aganglionic segment
M:F 4:1 Down syndrome (10%)and (5%) serious neurologic abnormalities
1 in 5000 to 8000
Presents in neonatal period (failure to pass meconium; abdominal distention)
Risk of perforation, sepsis, enterocolitis, fluid disturbances
Acquired (Chagas disease)
Intestinal neuronal plexus develop from neural crest cellsmigrate to the bowel during development
SporadicFamilial
Gentic defects:Endothelin 3GCDGFReceptor tyrosine kinase
Enterocolitis
Infectious Necrotizing Pseudomembranous
Infectious-Viral (Rotavirus, Norwalk)-Bacterial E. coli; Shigella; V. Cholerae; C. difficile-Parasites and protozoa (nematodes; flatworms; protozoa -Giardia lambdia; E. histolytica)
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
Multifactorial - immaturity of the gut’s immune system
Release of cytokines and endotoxins damages mucosa and blood supply
Terminal ileum or ascending colon
Edema to necrosis to gangrenous bowel
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 Bbinds to enteric receptorsinactivates RhO cytoplasmic proteinscausing injury to actin filaments andcell retraction
Dx: C. difficile cytotoxin in stoolResponse to tx is usually prompt Relapse occurs in up to 25% of px
Malabsorption
Defect in the assimilation of food (digestion and absorption)
Intraluminal stagea. Secretory Phase (Chronic pancreatitis/insufficiency)b. Biliary Phase (Biliary obstruction due to calculus of
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
Gluten, gliadin protein in wheat, oat, barley, and rye
hypersensitivity (immunologic) reaction to gluten
90-95% - HLA DQ heterodimer in Ch 6
Whites - rare in native Africans, Japanese, Chinese
Gluten - malabsorption -gluten free - improvement
Long term risk of malignancy -lymphoma (2X normal)
Distinct from Tropical sprue
Celiac disease: loss of villiincreased crypts, inflammation,intraepithelial lymphocytes,loss of brush border, goblet cells
Whipple disease
Rare Gram positive rod
shaped actinomycete: Tropheryma whippleli
Engulfed by macrophages (PAS positive diastase resistant)
Electron microscopy M:F 10:1
Inflammation
1. Miscellaneous-graft vs. host-drug induced-radiation enterocolitis-neutropenic colitis-diversion colitis
2. Acute appendicitis-etiology: bacteria-fecalith impairing
circulation, causing ischemia, necrosis and bacterial contamination
-acute abdomen -RLQ pain-McBurney’s point
-fever and leukocytosis
Inflammation
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
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 Class II locus on Ch 6
b. Abnormal host immunoreactivity
Crohn disease: Regional enteritis
1. Chronic inflammation involving all layers (transmural) of the SI
may occur at any point along the GI tract
primarily involving SI and LI
2. Mucosa shows linear ulceration and fistula
3. Segmental involvement/sparing
Serosal creeping fat
Crohn disease: Regional enteritis Inflammation spread
through the bowel wall to adjacent mesenteric fat
-characteristic non-caseating granulomas
tends to occur in young adults
increased incidence of cancer of SI and colon
diarrhea, crampy abdominal pain, fever
complications: fistula, obstruction, occult blood loss, Fe++ def anemia
malabsorption, malnutrition, weight loss
Ulcerative colitis1. Inflammation primarily
involving the mucosa of the colon
2. Diffuse, continuous inflammation that begins in the rectum and progresses proximally
3. Pseudopolyp formation4. Bloody diarrhea, from
ruptured vessels in inflamed mucosa
Toxic megacolon - rare complication - prominent dilatation and septic shock
Ulcerative colitis
Early phase: neutrophils accumulate within the depths of the crypts of Leiberkuhn forming crypt abscesses
Later phase: mucosa ulcerates and pseudo-polyps form
Late phase: after many years, mucosa becomes dysplastic, increasing risk of colon carcinoma
Between Crohn and UC, this finding is more commonly seen in:
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 UC Crohn UC Crohn UC Crohn both but more in UC Crohn both but more in UC Crohn UC
Vascular diseases:a. Ischemic bowel diseaseb. Angiodysplasiac. Hemorrhoids
Ischemic bowel disease -blood clot in mesenteric
artery causing ischemia, transmural infarction, necrosis of bowel, peritonitis
a.embolus: superior mesenteric artery
-source: embolus of heart (mural thrombus, valvular vegetation)
b. thrombus (arterial; venous: ATIII def, cirrhosis, OC)
c. hypoperfusion (non-occlusive): shock, CHF
50-75% death rateolder px with cardiac, vasc diseaseD/Dx: IBD
Vascular diseases:a. Ischemic bowel diseaseb. Angiodysplasiac. Hemorrhoids
Angiodysplasia -ectasia of veins -prone to rupture -GI bleeding -Osler-Weber-Rendu
syndrome (hereditary hemorrhagic telangiectasia)
Hemorrhoids -dilated veins of
hemorrhoidal plexus -Internal -External -(BRBPR or streaks on
stool), thrombosis, pain
Prevalence:<1%20% of significant LGI bleed
5% of populationelevated venous pressureconstipationstraining venous stasis of pregnancycollateral channels in portal HTNrare under 30 except in pregnant women
Non-neoplastic bowel diseasesa. Diverticular diseaseb. Herniasc. Adhesionsd. Intussusceptione. Volvulus
Diverticular disease: Diverticulosis and
Diverticulitis Acquired herniation Most common in left
colon; particularly sigmoid colon
Acute or chronic inflammation may occur
Perforation, peritonitis, fistula
Acquiredrare under 30western pop over 60prevalence: 50%
Non-neoplastic bowel diseasesa. Diverticular diseaseb. Herniasc. Adhesionsd. Intussuceptione. Volvulus
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)
Non-neoplastic bowel diseasesa. Diverticular diseaseb. Herniasc. Adhesionsd. Intussuceptione. Volvulus
Adhesions -string-like or band-like portions of scar tissue that
form during healing after surgery or peritonitis -may result in obstruction (kinking, compression)
Non-neoplastic bowel diseasesa. Diverticular diseaseb. Herniasc. Adhesionsd. Intussusceptione. Volvulus
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