Diseases of lower GI: Pathology

Question 1

Small Bowel Celiac Disease

Answer 1

exposure to alpha-gliadin peptide results in autoantibody formation

Question 2

Diagnosis of celiac (and path findings)

Answer 2

Serology: IgA Ab to tissue transglutaminase, anti-endomysial Ab

Endoscopy: “scalloped” mucosa of duodenum

Tissue biopsy: Villous blunting, increased intraepithelial lymphocytes, lymphoplasmacytosis of laminal propria

Question 3

Extra-intestinal complaints with celiac disease

Answer 3

Fatigue

 - Iron deficiency anemia
 - Pubertal delay, short stature
 - Aphthous stomatitis     

Associated with dermatitis herpetiformis blistering skin disease!!!!!!!!!!!!!!!!

Increased incidence of lymphocytic gastritis, lymphocytic colitis

Celiac-disease associated malignancies include enteropathy-associated T-cell lymphoma (EAT Lymphoma), and small intestinal adenocarcinoma

Question 4

Small Bowel Whipple Disease

Answer 4

Pathogenesis:

Caused by gram-positive bacilli Tropheryma whippelii

Bacilli absorbed by lamina propria macrophages

Organism-laden macrophages accumulate within the small intestinal lamina propria and mesenteric lymph nodes → lymphatic obstruction

Impaired lymphatic transport causes malabsorptive diarrhea

Clinical Features:
Triad of diarrhea, weight loss, malabsorption
Other common symptoms: arthritis, lymphadenopathy, neurologic disease
Typically presents in middle-aged or elderly white males

Diagnosis:
Tissue biopsy demonstrates the presence of the organisms

Question 5

Whipple Disease: Microscopic Findings

Answer 5

Villi distended by swollen macrophages

Macrophages filled with Whipple bacilli (PAS stain)

Question 6

Small bowel- infectious enterocolitis giardiasis

Answer 6

Giardia lamblia: parasitic enterocolitis

Protozoan parasite causing sporadic or epidemic diarrhea, waterborne and foodborne: In US, water is a major source of transmission (camping)

Cysts are resistant to chlorine –> filter necessary

7-14 day incubation period

Chronic diarrhea, malabsorption, flatulence, weight loss, may cause intermittent symptoms

Question 7

Microscopic findings of giardia

Answer 7

“schools of fish” of protozoans

Question 8

Large bowel infectious colitis

Answer 8

Infectious causes of colitis:
Bacterial enterocolitis
Pseudomembranous colitis
Viral gastroenteritis
Parasitic enterocolitis

Question 9

Bacterial infectious colitis

Answer 9

Mostly related to ingestion of contaminated water, food, or foreign travel

These infections typically create an acute self-limited colitis
Patients typically present several weeks after onset of symptoms, therefore tissue biopsy rarely shows classic acute infectious findings

Cholera
Campylobacter spp.
Shigellosis
Salmonellosis
Enteric (typhoid) fever
Yersinia spp.
Escherichia coli
Mycobacterial infection

Question 10

Campylobacter

Answer 10

Gram negative

Major cause of diarrhea worldwide

Produces a watery diarrhea +/- blood

Found in contaminated meat (poultry), water and unpasteurized dairy

C. jejuni commonly associated with food-borne gastroenteritis

C. fetus more often seen in immunosuppressed patients

Question 11

Salmonella

Answer 11

Gram-negative bacilli transmitted through food and water

Important cause of food poisoning and traveler’s diarrhea

Typhoid (enteric) Fever (S. typhimurium):

Abdominal pain, headache, fever; Abdominal rash and leukopenia; Diarrhea (not until 2nd week of infection) initially watery then bloody; Characteristic pathology most commonly seen in the ileum, colon, appendix and Peyer’s patches; Perforation and toxic megacolon possible

Non-Typhoid Salmonella species:

Mild self-limited gastroenteritis; Endoscopy: mucosal redness, ulceration and exudates

Question 12

E. coli

Answer 12

Enterohemorrhagic E. coli (O157:H7 is the most common strain)

Non-invasive, toxin-producing, contaminated hamburgers

Bloody diarrhea, severe cramps, mild or no fever, sometimes renal failure (HUS)

On endoscopy: edema, erosions, ulcers, hemorrhage (right colon mostly)

Deadly outbreaks

Question 13

Pseudomembranous Colitis

Answer 13

Most often caused by Clostridium difficile

Colitis often occurs after course of antibiotic therapy (“antibiotic-associated colitis”)

Most frequently implicated antibiotics are third-generation cephalosporins

Common in hospitalized patients (up to 30%)

Presents with fever, leukocytosis, abdominal pain, cramps, watery diarrhea

Toxins released cause disruption of epithelial cytoskeleton, tight junction barrier loss, cytokine release and apoptosis

Question 14

Histological findings in pseudomembranous colitis

Answer 14

Pseudomembranes: Adherent layer of inflammatory cells and mucinous debris at sites of colonic mucosal injury (A “volcano-like” eruption of neutrophils and mucinous debris attached to the surface epithelium)

Surface epithelium denuded, mucopurulent exudates

Question 15

Infectious enterocolitis- viral

Answer 15

Most cases of acute diarrhea are actually viral

Cytomegalovirus (mouth – anus)

Herpesvirus (esophagus and anorectum)

Enteric Viruses

Rotavirus:
Most common cause of severe childhood diarrhea and diarrheal mortality worldwide
Children btwn 6-24 months are most vulnerable
Dehydration
Vaccines now available

Question 16

Parasitic infections of colon

Answer 16

Common in other countries

Protozoal infections:
Prevalent pathogens in tropic and subtropical countries
Diagnosis is primarily by examination of stool samples

Entamoeba histolytica:
10% of world’s population is infected with E. histolytica parasite
Associated with a severe dysentery-like, fulminant colitis
Can disseminate to other sites (liver)
Cecum most commonly affected; “flask-shaped” ulcers in mucosa

Question 17

Histo findings with Entamoeba histolytica:

Answer 17

Flask-shaped ulcers with organisms in the mucous/fecal material

Question 18

Helminthic Infections

Answer 18

Worms

Most common method of diagnosing is by examination of stool for ova and parasites

Worldwide distribution, many people multiply infected

Cause of serious disease in nations with deficient sanitation systems, poor socioeconomic status and hot, humid climates

Seen in immigrants, patients who travel to endemic areas

Nutritional problems can be severe or life-threatening, especially in children

Question 19

Ascaris lumbricoides

Answer 19

(roundworm) a kind of helminth

One of most common parasites in humans

Most common in tropics

Ingested from soil contaminated with feces

Obstruction, perforation, growth retardation

Giant worms (up to 20cm) can be identified

Question 20

Ischemic colitis (clinical features, presentation, and histologic findings)

Answer 20

Clinical Features:
Older individuals with co-existing cardiac or vascular disease
Young patients: long-distance runners, women on oral contraceptives
Mechanical Obstruction: hernias, volvulus

Clinical presentation:
Acute transmural infarction: severe abdominal pain, tenderness, nausea and vomiting, bloody diarrhea and blood in stool
Peristaltic sounds disappear, rigid abdomen, shock, sepsis

Histologic Findings
Varies from focal acute mucosal necrosis to full-thickness necrosis

Question 21

Two most likely places for ischemic colitis

Answer 21

Watershed areas:

Splenic flecture

Rectosigmoid flecture

Question 22

Microscopic colitis

Answer 22

Chronic non-bloody watery diarrhea without weight loss
*Endoscopically normal *

Mucosal inflammation on biopsy

Middle aged women

NSAIDs implicated

2 types: Lymphocytic (Increased intraepithelial lymphocytes)
 and collagenous (Thickened subepithelial collagen layer)

Question 23

Biopsy findings for microscopic colitis

Answer 23

Tissue biopsy shows characteristic lymphocytic inflammation +/- a thickened subepithelial collagen layer

Question 24

Inflammatory bowel disease

Answer 24

IBD encompasses 2 distinct disorders
Crohn(‘s) disease (CD)
Ulcerative colitis (UC)

CD and UC have distinct gross (macroscopic), microscopic and clinical features

Similar epidemiology:
F>M
Most common among Caucasians
incidence of IBD 2-9x higher among Ashkenazi Jews
North America, Northern Europe, Australia
World-wide incidence rising

Question 25

Pathogenesis of IBD

Answer 25

Colitis results from a combination of defects:
Host interactions with intestinal microbiota
Intestinal epithelial dysfunction
Aberrant mucosal immune responses

Question 26

Crohn’s disease (clinical features and disease characteristics)

Answer 26

Clinical Features:
Variable

Intermittent attacks of relatively mild diarrhea, fever, abdominal pain

Diarrhea tends to not be bloody (as opposed to ulcerative colitis)

Relapsing and remitting disease

Extraintestinal manifestations (Uveitis, migratory polyarthritis, sacroiliitis, ankylosing spondylitis, erythema nodosum) all these an happen with UC too

Increased risk of colonic adenocarcinoma

Disease characteristics:
Skip lesions

Ileal involvement (“regional enteritis”)

Transmural chronic inflammation

Inflammatory strictures

Fissuring ulcers, sinus tracts, fistulae

Question 27

Ulcerative colitis (clinical features and disease characteristics)

Answer 27

ALWAYS RECTAL INVOLVEMENT

Clinical Features:

Bloody diarrhea or loose stools with lower abdominal pain, cramps

Symptoms relieved by defecation

Extraintestinal manifestations (Primary sclerosing cholangitis)

Increased risk of colonic adenocarcinoma

Disease characteristics:

Rectal involvement with retrograde continuous diffuse disease

No ileal involvement (except “backwash ileitis”)

Disease worse distally

Mucosal inflammation only – no transmural disease
No fissures, sinuses, fistula tracts

Question 28

Thickness of walls in Crohn’s and UC

Answer 28

Thickened in Crohn’s

Thinned in UC

Question 29

Microscopic findings in Crohn’s disease (Inflammation, pseudopolyps, uclers, lymphoid rxn, fibrosis, serositis, fistulae/sinus tracts)

Answer 29

Transmural inflammation
Moderate pseudopolyps
Deep, knife-like ulcers
Marked lymphoid rxn
Marked fibrosis
Marked serositis 
35% granulomas
Fistulae/sinus tracts

Question 30

Microscopic findings in UC (Inflammation, pseudopolyps, uclers, lymphoid rxn, fibrosis, serositis, fistulae/sinus tracts)

Answer 30

Inflammation limited to mucosa 
Marked pseudopolyps
Superficial, broad-based ulcers
Moderate lymphoid rxn
Mild to no fibrosis
Mild to no serositis 
No granulomas
No fistulae/sinus tracts

Question 31

Diverticular disease

Answer 31

Pathogenesis:
Results from decreased dietary fiber → decreased stool bulk → elevated intraluminal pressure → mucosal herniation through focal defects in the bowel wall

Clinical Features:
Most common in sigmoid colon
Prevalence approaches 60% in Western adult populations over age 60
Asymptomatic or intermittent cramping, lower abdominal discomfort

Question 32

Diverticulosis

Answer 32

presence of diverticula

Question 33

Diverticulitis

Answer 33

inflammation of the diverticula, usually secondary to obstruction

Question 34

Microscopic findings in diverticulosis

Answer 34

Diverticular outpouching lined by mucosa, submucosa, and variable amounts of muscularis propria

Question 35

Microscopic findings in diverticulitis

Answer 35

diverticulum becomes infiltrated with acute, then chronic inflammatory cells, and as the inflammation extends, the mucosa ulcerates and pericolonic abscesses, or sometimes fistula form

Question 36

Appendicitis

Answer 36

Clinical Features:
Most common in adolescents and young adults
Lifetime risk for appendicitis is 7%
M>F
Classic finding is McBurney’s sign, tenderness located 2/3 of the distance from the umbilicus to the right anterior superior iliac spine
Often presents as an acute abdomen
Appendectomy is treatment of choice; often laparoscopic

Pathogenesis:
Luminal obstruction by stone-like mass of stool “fecalith”→ ischemic injury and stasis of luminal contents → inflammatory response

Question 37

Microscopic findings in appendicitis

Answer 37

Mucosal ulceration

Transmural acute and chronic inflammation

Extension of inflammation into the mesoappendix

Question 38

Crypt architectural distortion

Answer 38

Path findings in both UC and Crohn’s

Chronic