GI Pathology I Flashcards
intestinal obstruction
*may occur at any level (small intestine most often)
*clinical manifestations - abdominal pain, distension, vomiting, constipation; surgical intervention usually required
*causes: hernias, intestinal adhesions, intussusception, volvulus
pathology of intestinal obstructions
*stasis and edema increase bulk of obstruction
*leads to arterial & venous compromise
*leads to tissue infarction
ischemic bowel disease
*acute compromise of major vessel
*most common > 70 years of age
*small bowel highly susceptible to ischemic injury
ischemic bowel disease - clinical manifestations
*sudden onset of cramping, LLQ abdominal pain
*decreased bowel sounds
*tenesmus
*bloody diarrhea
*severe cases may progress to shock/vascular collapse
causes of ischemic bowel disease
VASCULAR OCCLUSION:
1. arterial mesenteric thrombosis due to severe atherosclerosis
2. embolism: aortic atheromas, cardiac mural thrombi
3. mesenteric venous thrombosis (hypercoagulable states)
pathogenesis of ischemic bowel disease
2 phases:
1. initial hypoxic injury (at onset of vascular compromise)
2. reperfusion injury (at restoration of blood supply)
-leakage of gut lumen bacterial products into systemic circulation
-free radical production
-neutrophilic infiltration/inflammatory mediators
ischemic bowel disease - pathology
*damage can involve any or all bowel wall layers (mucosal layer is most susceptible)
*sharply defined demarcation: infarcted bowel intensely congested and dusky purple/red
*necrosis: early on, just the mucosa, but progresses to include more layers over time
malabsorption syndromes - overview
*defective absorption of fats, fat- and water-soluble vitamins, proteins, carbs, electrolytes and minerals, and water
*STEATORRHEA is hallmark
*examples:
-pancreatic insufficiency (cystic fibrosis)
-celiac disease
-Crohn disease
celiac disease - overview
*immune-mediated enteropathy caused by reaction to gluten
*worldwide growing incidence
*genetic susceptibility:
-HLA-DQ2
-HLA-DQ8
pathogenesis of celiac disease
- gluten (wheat storage protein) contains GLIADIN; gliadin resistant to further enzymatic digestion
- gliadin deaminated by tissue transglutaminase (tTG) and presented by APC to CD4+ T cells
- T cell cytokines damaging epithelium
4.** IgA antibody responses to tTG and gliadin** (markers of disease activity; uncertain pathogenic significance)
celiac disease - clinical features
1. pediatric celiac: irritability, abdominal distension, diarrhea, failure to thrive, anorexia, weight loss, muscle wasting
2. adults: most commonly between 30-60 yrs; bulky steatorrhea, abdominal bloating
*SYMPTOMS ABATE WITH DIETARY GLUTEN EXCLUSION
celiac disease - diagnosis
*detection of antibodies (IgA, or IgG if IgA deficient) to tTG and gliadin
*BIOPSY is beneficial for diagnosis
*symptoms abate with dietary gluten exclusion
complications of celiac disease
*dermatitis herpetiformis (an autoimmune blistering disease of the skin)
*increased incidence of enteropathy-associated T-cell lymphoma
celiac disease - gross morphology
*primarily affects distal duodenum and/or proximal jejunum
*rougher appearance
*more fissuring, large protrusions
*SCALLOPING ALONG THE FOLDS of the small bowel
celiac disease - microscopic morphology
*flat mucosa marked with villus atrophy (decreased surface area of the mucosal brush border, accounting for malabsorption
*intraepithelial T lymphocytosis
*crypt hyperplasia
pathogenesis of inflammatory bowel disease
*etiology unknown
1. mucosal immunity disruption (inadequate wound repair & epithelial barrier dysfunction; inadequate regulation of T cell responses)
2. host-microbial interactions (changes in gut microbiome contribute to inflammation)
3. defective autophagy contribute to dysregulated immune response
Crohn disease - definition
*chronic inflammatory disease of the terminal ileum/proximal colon associated with transmural inflammation and skip lesions
clinical features of Crohn disease
*diagnosis of exclusion
*relapsing diarrhea, RLQ pain, fever
*asymptomatic remission lasts weeks/months
*extra-intestinal involvement: uveitis, migratory polyarthritis, sacro-ileitis, ankylosing spondylitis, erythema nodosum, cutaneous granulomas
complications of Crohn disease
*increased risk of colonic adenocarcinoma in long-standing colonic disease
*fibrosing strictures and fistulas may develop, requiring surgical treatment
Crohn disease - gross pathology
*involves terminal ileum, ileocecal valve, cecum
*gross features:
-skip lesions (sharply delineated diseased areas separated by uninvolved gut)
*thickened intestinal wall: COBBLESTONE MUCOSA, strictures, CREEPING FAT
*fissures & fistulas
Crohn disease - microscopic pathology
*transmural edema, inflammation, fibrosis
*mucosal architecture distortion with branched glands
*lymphoid aggregates
*noncaseating GRANULOMAS
ulcerative colitis - definition
*chronic inflammatory disease diffusely involving the mucosa of the colon and rectum
note - colectomy is curative
clinical features of ulcerative colitis
*diagnosis of exclusion
*relapsing BLOODY diarrhea, LLQ pain, fever
*asymptomatic remission lasts weeks/months
*extra-intestinal involvement: primary sclerosing cholangitis, migratory polyarthritis, sacro-ileitis, ankylosing spondylitis, uveitis
complications of ulcerative colitis
increased risk of colonic adenocarcinoma in long-standing colonic disease
ulcerative colitis - gross pathology
*always involves rectum with CONTIGUOUS spread (small bowel not affected)
*gross features:
-granular mucosal surface with ulcerations
-pseudopolyps (protruding islands of regenerative epithelium)
-no transmural thickening
ulcerative colitis - microscopic pathology
*contiguous inflammation without skips
*limited to mucosa/submucosa
*CRYPT ABSCESSES (neutrophils within glands)
*mucosal architectural distortion
*possible glandular dysplasia
pathogenesis of colorectal carcinoma
- classic adenoma to carcinoma sequence:
-APC/beta-catenin pathways
-80% carcinomas
-familial adenomatous polyposis - hereditary non-polyposis colorectal carcinoma (Lynch syndrome):
-microsatellite instability (MSI) - DNA mismatch repair deficiency
-mutations accumulate in microsatellite repeats
-increased risk of endometrial carcinoma too
colorectal carcinoma of cecum/ascending colon - gross pathology
-raised, exophytic polyps
-extend along one wall (rarely cause obstruction)
-MSI
-iron deficiency anemia
colorectal carcinoma of rectosigmoid/left side - gross pathology
-annular “napkin ring”
-constrictive with luminal narrowing, causing obstruction
-APC pathway
colorectal carcinoma - microscopic pathology
*epithelial dysplasia
*invasive glands (differentiation depends on glands +/- mucin formation)
*stromal desmoplasia/fibrosis
colon polyps
*epithelial cell proliferation with protuberance into lumen
*very common
-growth pattern: pedunculated = stalk; or sessile = without stalk
-nonneoplastic = hyperplastic, inflammatory, hamartomatous
-neoplastic = adenoma
hyperplastic colon polyps
*non-neoplastic = no malignant potential (difficult to distinguish from sessile serrated adenomas, thus frequently biopsied)
-common in elderly, discovered during routine colonoscopy
*increased goblet cells with IRREGULAR GLANDS (hyperplasia of goblet cells)
colon polyps - adenomas
*neoplastic = POTENTIAL for malignant transformation
*present in 50% of adults > 50 years
*may be pedunculated or sessile
*epithelial dysplasia = nuclear atypia, stratification
-loss of goblet cells
-may be tubular, villous, serrated
