Diseases of lower GI: Pathology Flashcards
Small Bowel Celiac Disease
exposure to alpha-gliadin peptide results in autoantibody formation
Diagnosis of celiac (and path findings)
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
Extra-intestinal complaints with celiac disease
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
Small Bowel Whipple Disease
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
Whipple Disease: Microscopic Findings
Villi distended by swollen macrophages
Macrophages filled with Whipple bacilli (PAS stain)
Small bowel- infectious enterocolitis giardiasis
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
Microscopic findings of giardia
“schools of fish” of protozoans
Large bowel infectious colitis
Infectious causes of colitis: Bacterial enterocolitis Pseudomembranous colitis Viral gastroenteritis Parasitic enterocolitis
Bacterial infectious colitis
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
Campylobacter
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
Salmonella
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
E. coli
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
Pseudomembranous Colitis
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
Histological findings in pseudomembranous colitis
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
Infectious enterocolitis- viral
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
Parasitic infections of colon
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
Histo findings with Entamoeba histolytica:
Flask-shaped ulcers with organisms in the mucous/fecal material
Helminthic Infections
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
Ascaris lumbricoides
(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
Ischemic colitis (clinical features, presentation, and histologic findings)
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
Two most likely places for ischemic colitis
Watershed areas:
Splenic flecture
Rectosigmoid flecture
Microscopic colitis
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)
Biopsy findings for microscopic colitis
Tissue biopsy shows characteristic lymphocytic inflammation +/- a thickened subepithelial collagen layer
Inflammatory bowel disease
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
Pathogenesis of IBD
Colitis results from a combination of defects:
Host interactions with intestinal microbiota
Intestinal epithelial dysfunction
Aberrant mucosal immune responses
Crohn’s disease (clinical features and disease characteristics)
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
Ulcerative colitis (clinical features and disease characteristics)
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
Thickness of walls in Crohn’s and UC
Thickened in Crohn’s
Thinned in UC
Microscopic findings in Crohn’s disease (Inflammation, pseudopolyps, uclers, lymphoid rxn, fibrosis, serositis, fistulae/sinus tracts)
Transmural inflammation Moderate pseudopolyps Deep, knife-like ulcers Marked lymphoid rxn Marked fibrosis Marked serositis 35% granulomas Fistulae/sinus tracts
Microscopic findings in UC (Inflammation, pseudopolyps, uclers, lymphoid rxn, fibrosis, serositis, fistulae/sinus tracts)
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
Diverticular disease
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
Diverticulosis
presence of diverticula
Diverticulitis
inflammation of the diverticula, usually secondary to obstruction
Microscopic findings in diverticulosis
Diverticular outpouching lined by mucosa, submucosa, and variable amounts of muscularis propria
Microscopic findings in diverticulitis
diverticulum becomes infiltrated with acute, then chronic inflammatory cells, and as the inflammation extends, the mucosa ulcerates and pericolonic abscesses, or sometimes fistula form
Appendicitis
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
Microscopic findings in appendicitis
Mucosal ulceration
Transmural acute and chronic inflammation
Extension of inflammation into the mesoappendix
Crypt architectural distortion
Path findings in both UC and Crohn’s
Chronic
