GI Pathology I

Question 1

intestinal obstruction

Answer 1

*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

Question 2

pathology of intestinal obstructions

Answer 2

*stasis and edema increase bulk of obstruction
*leads to arterial & venous compromise
*leads to tissue infarction

Question 3

ischemic bowel disease

Answer 3

*acute compromise of major vessel
*most common > 70 years of age
*small bowel highly susceptible to ischemic injury

Question 4

ischemic bowel disease - clinical manifestations

Answer 4

*sudden onset of cramping, LLQ abdominal pain
*decreased bowel sounds
*tenesmus
*bloody diarrhea
*severe cases may progress to shock/vascular collapse

Question 5

causes of ischemic bowel disease

Answer 5

VASCULAR OCCLUSION:
1. arterial mesenteric thrombosis due to severe atherosclerosis
2. embolism: aortic atheromas, cardiac mural thrombi
3. mesenteric venous thrombosis (hypercoagulable states)

Question 6

pathogenesis of ischemic bowel disease

Answer 6

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

Question 7

ischemic bowel disease - pathology

Answer 7

*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

Question 8

malabsorption syndromes - overview

Answer 8

*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

Question 9

celiac disease - overview

Answer 9

*immune-mediated enteropathy caused by reaction to gluten
*worldwide growing incidence
*genetic susceptibility:
-HLA-DQ2
-HLA-DQ8

Question 10

pathogenesis of celiac disease

Answer 10

1. gluten (wheat storage protein) contains GLIADIN; gliadin resistant to further enzymatic digestion
2. gliadin deaminated by tissue transglutaminase (tTG) and presented by APC to CD4+ T cells
3. T cell cytokines damaging epithelium
4. IgA antibody responses to tTG and gliadin (markers of disease activity; uncertain pathogenic significance)

Question 11

celiac disease - clinical features

Answer 11

*pediatric celiac: irritability, abdominal distension, diarrhea, failure to thrive, anorexia, weight loss, muscle wasting
*adults: most commonly between 30-60 yrs; bulky steatorrhea, abdominal bloating
*SYMPTOMS ABATE WITH DIETARY GLUTEN EXCLUSION

Question 12

celiac disease - diagnosis

Answer 12

*detection of antibodies to tTG and gliadin
*BIOPSY is beneficial for diagnosis
*symptoms abate with dietary gluten exclusion

Question 13

complications of celiac disease

Answer 13

*dermatitis herpetiformis (an autoimmune blistering disease of the skin)
*increased incidence of enteropathy-associated T-cell lymphoma

Question 14

celiac disease - gross morphology

Answer 14

*primarily affects distal duodenum and/or proximal jejunum
*rougher appearance
*more fissuring, large protrusions
*SCALLOPING ALONG THE FOLDS of the small bowel

Question 15

celiac disease - microscopic morphology

Answer 15

*flat mucosa marked with villus atrophy (decreased surface area of the mucosal brush border, accounting for malabsorption
*intraepithelial T lymphocytosis
*crypt hyperplasia

Question 16

pathogenesis of inflammatory bowel disease

Answer 16

*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

Question 17

Crohn disease - definition

Answer 17

*chronic inflammatory disease of the terminal ileum/proximal colon associated with transmural inflammation and skip lesions

Question 18

clinical features of Crohn disease

Answer 18

*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

Question 19

complications of Crohn disease

Answer 19

*increased risk of colonic adenocarcinoma in long-standing colonic disease
*fibrosing strictures and fistulas may develop, requiring surgical treatment

Question 20

Crohn disease - gross pathology

Answer 20

*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

Question 21

Crohn disease - microscopic pathology

Answer 21

*transmural edema, inflammation, fibrosis
*mucosal architecture distortion with branched glands
*lymphoid aggregates
*noncaseating GRANULOMAS

Question 22

ulcerative colitis - definition

Answer 22

*chronic inflammatory disease diffusely involving the mucosa of the colon and rectum

note - colectomy is curative

Question 23

clinical features of ulcerative colitis

Answer 23

*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

Question 24

complications of ulcerative colitis

Answer 24

increased risk of colonic adenocarcinoma in long-standing colonic disease

Question 25

ulcerative colitis - gross pathology

Answer 25

*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

Question 26

ulcerative colitis - microscopic pathology

Answer 26

*contiguous inflammation without skips
*limited to mucosa/submucosa
*CRYPT ABSCESSES (neutrophils within glands)
*mucosal architectural distortion
*possible glandular dysplasia

Question 27

pathogenesis of colorectal carcinoma

Answer 27

1. classic adenoma to carcinoma sequence:
   -APC/beta-catenin pathways
   -80% carcinomas
   -familial adenomatous polyposis
2. hereditary non-polyposis colorectal carcinoma
   -microsatellite instability (MSI) - DNA mismatch repair deficiency
   -mutations accumulate in microsatellite repeats
   -Lynch Syndrome

Question 28

colorectal carcinoma of cecum/ascending colon - gross pathology

Answer 28

-raised, exophytic polyps
-extend along one wall (rarely cause obstruction)
-MSI
-iron deficiency anemia

Question 29

colorectal carcinoma of rectosigmoid/left side - gross pathology

Answer 29

-annular “napkin ring”
-constrictive with luminal narrowing, causing obstruction
-APC pathway

Question 30

colorectal carcinoma - microscopic pathology

Answer 30

*epithelial dysplasia
*invasive glands (differentiation depends on glands +/- mucin formation)
*stromal desmoplasia/fibrosis

Question 31

colon polyps

Answer 31

*epithelial cell proliferation with protuberance into lumen
*very common
-growth pattern: pedunculated = stalk; or sessile = without stalk
-nonneoplastic = hyperplastic, inflammatory, hamartomatous
-neoplastic = adenoma

Question 32

hyperplastic colon polyps

Answer 32

*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)

Question 33

colon polyps - adenomas

Answer 33

*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