Diseases of Lower GI Tract Flashcards
Celiac Disease
-Gluten (wheat, barley, rye) digested by luminal and brush-border enzymes –>exposure to α-gliadin peptide results in autoantibody formation–>inflammation–>villous atrophy–>tissue damage–loss of mucosal and brush border surface area –>malabsorption, diarrhea
Host Factors:
Class II HLA DQ2 or DQ8
Assoc w/ Type 1 DM, thyroiditis, Sjögren syndrome
Clinical features:
Pediatric vs Adult
CLASSICAL: Bulky fatty diarrhea, flatulence, weight loss, anemia, nutritional deficiencies, growth failure in children
ATYPICAL: Minor gastrointestinal complaints but other stuff: anemia, dental enamel defects, infertility, arthritis
Dx of Celiac Disease
Endoscopy: loss of surface villi; “scalloped mucosa in duodenum”
Serology (1st): IgA antibodies to tissue transglutaminase Anti-endomysial antibodies
- **Tissue (biopsy):
- villous blunting
- increased intraepithelial lymphocytes
- lymphoplasmacytosis of the lamina propria
Histologic severity doesn’t always correlate with symptoms
Extraintestinal complains of Celiac disease
- Fatigue
- Iron deficiency anemia
- Pubertal delay, short stature
- Aphthous stomatitis
- **Associated with dermatitis herpetiformis blistering skin disease
- lymphocytic gastritis and lymphocitic colitis
- enteropathy-associated T cell lymphoma (EAT Lymphoma) and small intestinal adenocarcinoma
Whipple Disease
Small bowel
Pathogenesis:
-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
Dx: biopsy shows organisms
PAS stain.
Giardia lamblia
-Parasitic enterocolitis
-Protozoan parasite causing sporadic or epidemic diarrhea, waterborne and foodborne–> In US, *water.
Cysts are resistant to chlorine –> filter necessary
7-14 day incubation period
Chronic diarrhea, malabsorption, flatulence, weight loss, may cause intermittent symptoms
-Most often in duodenum
“schools of fish”
Infectious enterocolitis (bacterial infectious)
- ingestion of contaminated food, water, foreign travel
- acute self ltd colitis
Cholera Campylobacter spp. Shigellosis Salmonellosis Enteric (typhoid) fever Yersinia spp. Escherichia coli Mycobacterial infection
Mostly viral
Campylobacter spp
Infectious enterocolitis
Gram-negative bacteria; major cause of diarrhea worldwide
A leading cause of bacterial foodborne illness in US
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
Infectious EnterocolitisSalmonella
Gram-negative bacilli transmitted through food and water
-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
Infectious Enterocolitis Escherichia coli
*Enterohemorrhagic E coli
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
Infectious Enterocolitis Pseudomembranous Colitis
Clinical Features:
Most often caused by Clostridium difficile
Colitis often occurs after course of antibiotic therapy (“antibiotic-associated colitis”)
Most frequently are third-generation cephalosporins
Common in hospitalized patients (up to 30%)
—>fever, leukocytosis, abdominal pain, cramps, watery diarrhea
–found on fomites
Pathogenesis
Disruption of normal colonic flora by antibiotic allows C. difficile overgrowth → toxins released cause disruption of epithelial cytoskeleton, tight junction barrier loss, cytokine release and apoptosis
Histologic Findings
Pseudomembranes
-Adherent layer of inflammatory cells and mucinous debris at sites of colonic mucosal injury
-Surface epithelium denuded, mucopurulent exudates
Pseudomembrane
A “volcano-like” eruption of neutrophils and mucinous debris attached to the surface epithelium
Infectious Enterocolitis Viral Infections
Cytomegalovirus (mouth – anus)
Herpesvirus (esophagus and anorectum)
Enteric Viruses:
-***Rotavirus
Most common cause of severe childhood diarrhea and diarrheal mortality worldwide
Children between 6 – 24 months are most vulnerable
-infects and destroys mature enterocytes → villus surface repopulated by immature secretory cells → loss of absorptive function → net secretion of water and electolytes → osmotic diarrhea –>DEHYDRATION
Two vaccines now available; previous had risk of intussusception
Protozoal infections (parasitic)
Prevalent pathogens in tropic and subtropical countries
Diagnosis is primarily by examination of stool samples
Entamoeba histolytica
-parasitic infections (infectious enterocolitis)
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
Helminthic infections
- Dx by examinaing stool for ova, parasites
- worldwide distrib
- serious disease in areas with deficient sanitiation systems, poor SES, hot humid climates
- immigrants
- can be severe/life threatening esp in kids
Ascaris lumbricoides (roundworm)
- helminth
- common, esp in tropics
- soil contaminated w/ feces
- Obstruction, perforation, growth retardation
- Giant worms (up to 20cm)
Ischemic Colitis
Clinical Features
Older individuals with co-existing cardiac or vascular disease
Young patients: long-distance runners, women on oral contraceptives
Mechanical Obstruction: hernias, volvulus
Pathogenesis
Lack of blood flow due to:
Low cardiac output
Occlusive disease of vascular supply to bowel
Diagnosis
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
Most vulnerable: splenic flexure and rectosigmoid area
regeneration: lamina propria fibrosis, withered atrophic crypts
Two most at risk areas for ischemic colitis
Most vulnerable: splenic flexure and rectosigmoid area
Two types of microscopic collitis
collagenous colitis
lymphocytic colitis
Microscopic colitis
Clinical Features
Chronic watery diarrhea
Presents primarily in middle-aged and older women
NSAIDs implicated
Diagnosis
Endoscopy: Normal
Tissue biopsy shows characteristic lymphocytic inflammation +/- a thickened subepithelial collagen layer
Clinical Notes
Lymphocytic colitis shows a strong association with celiac disease, lymphocytic gastritis and other autoimmune diseases such as thyroiditis
collagenous colitis findings on histology
thickened subepithelial collagen layer
- brittle
- results in sloughing of epithelium
lymphocytic colitis histology findings
increased intraepithelial lymphocytes
Inflammatory Bowel Disease: 2 disorders
Crohns disease
Ulcerative colitis
Similarities
F>M
Most common among Caucasians”
- incidence of IBD 2-9x higher among Ashkenazi Jews
-North America, Northern Europe, Australia
-World-wide incidence rising
IBD Pathogenesis
-not truly autoimmune disease but can be considered in that way
-Colitis results from a combination of defects:
Host interactions with intestinal microbiota
Intestinal epithelial dysfunction
Aberrant mucosal immune responses
Crohns Disease
Variable
Intermittent attacks of relatively mild diarrhea, fever, abdominal pain
Diarrhea tends to no be bloody (as opposed to ulcerative colitis)
Relapsing and remitting disease
Extraintestinal manifestations:
Uveitis, migratory polyarthritis, sacroiliitis, ankylosing spondylitis, erythema nodosum
Increased risk of colonic adenocarcinoma
Skip lesions Ileal involvement (“regional enteritis”) Transmural chronic inflammation Inflammatory strictures Fissuring ulcers, sinus tracts, fistulae -mouth to anus could be affected (whole GI tract)****
Ulcerative Colitis
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
**always rectal involvement (spared often in Crohns)
IBD and cancer risk
risk of adenocarcinoma similar in colonic disease and UC (~10% risk) related to:
Duration of disease
Extent of disease (pancolitis vs localized involvement)
Family history
Extra-intestinal manifestations (i.e. primary sclerosing cholangitis)
Endoscopic surveillance includes assessment of disease activity and dysplasia, the precursor to adenocarcinoma
Distribution, bowel involvement, strictures, wall appearance for crohns vs UC
Crohns: skip lesions ileum +/- colon strictures yes wall thickened
UC diffuse distrib colon only rare strictures thinned wall
Pseudopolyps
marked in UC, moderate in Crohns
Granulomas
35% in Crohns
Not in UC
IBD Microscopic findings
Inflammation: transmural in Crohns, ltd to mucosa in UC
pseudopolyps: moderate in crohns, marked in UC
ulcers: deep knife like in Crohns, superficial broad based in uc
lymphoid rxn: marked in crohns, moderate in uc
fibrosis: marked in crohns, mild to none in UC
serositis: marked in crohns, uc mild to none
granulomas: yes (35%) crohns, none ?UC
Fistulae/sinus tracts: yes crohns, no UC
Diverticular Disease
A diverticulum is an outpouching/herniation of the mucosa and submucosa
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
diverticulosis
presence of diverticula
diverticulitis
inflammation of diverticula
-often due to stool
Diverticular disease microscopic findings
Diverticular outpouching lined by mucosa, submucosa, and variable amounts of muscularis propria = diverticulosis
Mucosa is compressed/flattened
In diverticulitis the diverticulum becomes infiltrated with acute, then chronic inflammatory cells, and as the inflammation extends, the mucosa ulcerates and pericolonic abscesses, or sometimes fistula form.
complications of diverticulitis
complications include:
- obstruction
- perforation
- abscess formation
- bleeding
Tx: usually surgical
Appendix
part of large bowel
Appendicitis
Most common in adolescents and young adults
Lifetime risk 7%
M>F
Classic finding is McBurney’s sign
Often presents as an acute abdomen
Appendectomy is treatment of choice; often laparoscopic
Pathogenesis
Luminal obstruction “fecalith”→ ischemic injury and stasis of luminal contents → inflammatory response
Appendicitis microscopic findings
Mucosal ulceration
Transmural acute and chronic inflammation
Extension of inflammation into the mesoappendix
