Pathology of Lower GI Tract Flashcards
Celiac disease (“Gluten-Sensitive Enteropathy”) pathogenesis
- Gluten (wheat, barley, rye) digested by luminal and brush-border enzymes ==> α-gliadin peptide complexes with tissue transglutaminase (tTG)
- cross-linked molecules ==> autoantibody formation
- → inflammation ( ↑ T-lymphocytes) → villous atrophy → tissue damage → loss of mucosal and brush-border surface area → malabsorption, diarrhea
Common associations/genetics of Celiac Disease
- Genetic associations: Class II HLA-DQ2 or HLA-DQ8 allele
- Association with other autoimmune diseases:
- Type 1 DM
- thyroiditis
- Sjögren syndrom
Diagnostic histologic features of Celiac disease
- villous blunting
- increased intraepithelial lymphocytes
- lymphoplasmacytosis of the lamina propria
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Pathogenesis of Whipple Disease
- 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 presenation/dx of Whipple disease
- Sx:
- Triad of diarrhea, weight loss, malabsorption
- Other common symptoms: arthritis, lymphadenopathy, neurologic disease
- Typically presents in middle-aged or elderly white males
- Dx
- tissue biopsy demonstrates presence of T. whippelii
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Infectious vs. Non-infectious causes of colitis
- Infectious causes of colitis
- Bacterial enterocolitis
- Pseudomembranous colitis
- Viral gastroenteritis
- Parasitic enterocolitis
- Non-infectious causes of colitis
- Ischemic colitis
- Microscopic colitis
Major causes of bacterial infectious enterocolitis
- Campylovacter spp.
- Shigellosis
- Salmonellosis
- Escherichia coli
Characteristics of Campylobacter spp. infection
- major cause of diarrhea worldwide
- gram-neg.
- ===> watery diarrhea +/- blood
- found in contaminated poultry, water, unpasteurized dairy
Characteristics of Shigella infection
- major cause of infectious diarrhea
- virulent, invasive gram-negative bacilli
- ==> severe watery or bloody diarrhea
- transmitted by water contaminated w/feces
Characteristics of Salmonella infection
- prevalent where sanitation is poor
- **important cause of food poisoning/traveller’s diarrhea
- gram-negative bacilli
- transmitted trhough food, water
Characteristics of E. Coli infections
- Enterotoxigenic E. Coli
- non-invasive ==> non-bloody diarrhea
- Enteroinvasive E. coli
- invasive (similar to Shigella)
- ==> non-bloody diarrhe, dysentery-like illness
- contaminated cheese, water, person-to-person
- Enterohemorrhagic E. coli
- contaminated hamburgers
- ==> bloody diarrhea, severe cramps
- Enteroadherent E. coli
- non-invasive ==> non-bloody diarrhea
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Characteristics of pseudomembranous colitis
- clinical
- usually C. diff
- commonly following course of antibiotics
- e.g. 3rd gen cephalosporings
- hospitalized pts
- fever, leukocytosis, abd. pain, cramps, watery diarrhea
- histo findings
- Pseudomembranes
- Adherent layer of inflammatory cells and mucinous debris at sites of colonic mucosal injury
- Surface epithelium denuded, mucopurulent exudates
- Pseudomembranes
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Viral causes of infectious enterocolitis
- cytomegalovirus
- herpresvirus
- enteric viruses
- rotavirus
- adenovirus
- norovirus
Dx?
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Pseudomembranous colitis
Parasitic causes of infectious enterocolitis
- prevalent pathogens in tropic and subtropical countries
- entamoeba histolytica
- giardia lamblia
- cryptosporidium parvum
- helminthic infections
- ascaris lumbricoides (roundworm)
- strongylides stercoralis (nematode)
- schistosomiasis (trematode)
Clinical features and presentation of ischemic colitis
- Older individuals with co-existing cardiac or vascular disease
- Young patients: long-distance runners, women on oral contraceptives
- Mechanical Obstruction: hernias, volvulus
- Presentation:
- Acute transmural infarction: severe abdominal pain, tenderness, nausea and vomiting, bloody diarrhea and blood in stool
- Peristaltic sounds disappear, rigid abdomen, shock, sepsis
Pathogenesis & Histologic findings in ischemic colitis
- Pathogenesis:
- decreased blood flow due to:
- low CO
- occlusive dz of bowel vascular supply
- decreased blood flow due to:
- Histologic findings
- acute mucosal necrosis vs. full-thickness necrosis
Common locations of ischemic colitis
- @ splenic flexure = superior & inferior mesenteric artery watershed
- @ sigmoid colon = inferior and hypogastric artery watershed
Dx?
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- mucosal necrosis in context of ischemic colitis
Dx?:
- chronic, non-bloody watery diarrhea
- no weight loss
- normal endoscopic exam
- mucosal inflammation on biopsy
- microscopic colitis
- collagenous colitis
- lymphocytic colitis
Characteristics of microscopic colitis
- •Clinical Features
- •Presents primarily in middle-aged and older women
- •NSAIDs implicated
- •Diagnosis
- •Endoscopy: Normal
- •Tissue biopsy shows characteristic lymphocytic inflammation +/- a thickened subepithelial collagen layer
- Major types=
- collagenous colitis
- lymphocytic
- strong association with celiac disease, lymphocytic gastritis and other autoimmune diseases such as thyroiditis
*
- strong association with celiac disease, lymphocytic gastritis and other autoimmune diseases such as thyroiditis
Histologic characteristics of collagenous colitis
- thickened supepithelial collagen band +
- lymphocytic inflammation
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Dx?
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- microscopic collagenous colitis
Dx?
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- microscopic lymphocytic colitis
- feature = increased intraepithelial lymphocytes
Histologic features of lymphocytic colitis
- increased intraepithelial lymphocytes
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Clinical features of Crohn’s disease
- •Variable
- •Intermittent attacks of relatively mild diarrhea, fever, abdominal pain
- •Bloody diarrhea
- •Relapsing and remitting disease
- •Extraintestinal manifestations
- •Uveitis, migratory polyarthritis, sacroiliitis, ankylosing spondylitis, erthyema nodosum
- •Increased risk of colonic adenocarcinoma
Disease characteristics of Crohn’s disease
- Skip lesions
- Ileal involvement (“regional enteritis”)
- Transmural chronic inflammation
- Inflammatory strictures
- Fissuring ulcers, sinus tracts, fistulae
Clinical features of ulcerative colitis
- Bloody diarrhea with stringy, mucoid material, lower abdominal pain, cramps
- Symptoms relieved by defecation
- Extraintestinal manifestations
- Primary sclerosing cholangitis
- Increased risk of colonic adenocarcinoma
Disease characteristics of ulcerative colitis
- 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
Macroscopic findings: Crohn’s vs. Ulcerative Colitis
- Distribution of disease
- Crohn’s: Skip lesions
- UC: Diffuse
- Bowel involved
- Crohn’s: Ileum +/- colon
- UC: Colon only
- Strictures
- Crohn’s: Yes
- UC: Rare
- Wall appearance
- Crohn’s: Thickened
- UC: Thinned
Microscopic findings: Crohn’s vs. Ulcerative Colitis
- Inflammation
- Crohn’s: Transmural
- UC: Limited to the mucosa
- Pseudopolyps
- Crohn’s: Moderate
- UC: Marked
- Ulcers
- Crohn’s: Deep, knife-like
- UC: Superficial, broad-based
- Lymphoid reaction
- Crohn’s: Marked
- UC: Moderate
- Fibrosis
- Crohn’s: Marked
- UC: Mild to none
- Serositis
- Crohn’s: Marked
- UC: Mild to none
- Granulomas
- Crohn’s: Yes (35%)
- UC: No
- Fistulae/sinus tracts
- Crohn’s: Yes
- UC: No
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Dx?
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Crohn’s disease
Dx?
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Ulcerative colitis
Dx?
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- feature = inflammatory “pseudo” polyp
- dx = ulcerative colitis
Dx?
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- feature = fissuring ulcers
- dx = crohn’s disease
Dx?
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- feature = granuloma
- dx = crohn’s disease
Pathogenesis of diverticular disease
- Results from decreased dietary fiber → decreased stool bulk → elevated intraluminal pressure → mucosal herniation through focal defects in the bowel wall
- Defects or gaps in the bowel wall are created where nerves, arterial vasa recta and their connnective tissue sheaths penetrate the inner circular muscle coat
- These gaps are reinforced by the external longitudinal layer of the muscualris propria, which in the colon is gathered into 3 bands, the taeniae coli
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Clinical features of diverticular disease
- 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
Clinical features of appendicitis
- 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
Microscopic/histologic findings in appendicitis
- Mucosal ulceration
- Transmural acute and chronic inflammation
- Extension of inflammation into the mesoappendix
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Dx?
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