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v. Micro: absence of ganglion cells in Auerbach and Meissner plexuses vi. Diagnosis: rectal biopsy vii. Treatment: resection of affected segment . Malabsorption syndromes a. Celiac sprue i. Synonyms: glu ten-sensitive enteropathy, nontropical sprue ii. Definition: hypersensitivity to gluten (and gliadin), resulting in loss of small bowel villi and malabsorption iii. Genetic predisposition: HLA-B8, DR3, and DQ

iv. Micro

■ Increased intraepithelial lymphocytes

• Increased plasma cells in the lamina propria v. Presentation

■ Usually presents in childhood with malabsorption

■ Abdominal distention, bloating, and flatulence

• Diarrhea, steatorrhea, and weight loss vi. Associated with dermatitis herpetiformis vii. Treatment: dietary restriction of gluten b. Tropical sprue i. Definition: ma]absorptive disease of unknown etiology (infection and/or nutritional deficiency) affecting travelers to tropical regions, such as the Caribbean and South America ii. Micro: similar to celiac sprue iii. Treatment: antibiotics, vitamin B12, and folate c. Whipple disease i. Definition: rare infectious disease involving many organs, including small intestines, joints, lung, heart, liver, spleen, and CNS

ii. Caucasian males; age 30-50 years iii. Organism: Trophermyma whippleii iv. Presentation: malabsorption, weight loss, and diarrhea v. Micro: small bowel lamina propria is filled with macrophages stuffed with PAS-positive, rod-shaped bacilli vi. Treatment: antibiotics Inflammatory bowel disease a. Three major categories i. Crohn disease (CD) (synonym: regional enteritis)

ii. Ulcerative colitis (UC)

iii. Colitis of indeterminate type b. Epidemiology i. Females > males ii. Caucasians > non-Caucasians iii. Age distribution

■ CD: bimodal with peaks at ages 10-30 and 50-70 years

■ UC: peaks at age 20-30 years iv. Increasing incidence v. Ulcerative colitis is more common than Crohn disease c. Presentation i. Episodes of bloody diarrhea or stools with mucns ii. Crampy lower abdominal pain iii. Fever iv. Perianal fistulas (CD)

v. Extraintestinal manifestations (UC > CD)

vi. CD of the small bowel may present with malabsorption vii. CD may mimic appendicitis d. Diagnosis i. Diagnosis of exclusion ii. Endoscopy and biopsy

Table 15-1. Crohn Disease Versus Ulcerative Colitis

I Crohn Disease

Ulcerative Colitis

Most common site

Terminal ileum

Rectum

Distribution

Mouth to anus

Rectum —» colon "back-wash" ileitis

Spread

D is con tin u o u s/"skip"

Continuous

Gross features

• Focal aphthous ulcers with intervening normal mucosa

• Linear fissures

• Cobblestone

• Thickened bowel wall ■ "Creeping fat"

Extensive ulceration Pseudopolyps

Micro

Noncaseating granulomas

Crypt abscesses

Inflammation

Transmural

Limited to mucosa and submucosa

• "String sign" on barium studies

■ Obstruction

• Sinus tracts

Toxic megacolon

Genetic association

HLA-E27

Extraintestinal manifestations

Uncommon

Common (e.g., arthritis, spondylitis, primary sclerosing cholangitis, erythema nodosum, pyoderma gangrenosum)

Cancer risk

Slight 1-3%

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Miscellaneous conditions a. Ischemic bowel disease i. Definition: decreased blood flow and ischemia of the bowel secondary to atherosclerosis with thrombosis, thromboembolism, or reduced cardiac output from shock ii. Most common in older individuals iii. Presentation: abdominal pain and bloody diarrhea iv. Distribution: tends to affect watershed areas (e.g., splenic flexure)

v. Gross: hemorrhagic infarction vi. Treatment: surgical resection vii. Prognosis: poor; over 50% mortality b. Hemorrhoids i. Definition: tortuous dilated submucosal veins caused by increased venous pressure ii. Risk factors

Constipation and prolonged straining during bowel movements

Cirrhosis iii. Complications

• Thrombosis (painful)

• Bleeding (streaks of bright red blood on hard stool)

c. Angio dysplasia i. Definition: arteriovenous malformations of the intestines ii. Common in individuals over age 55

iii. Occur in the cecum and right colon iv. Presentation: multiple episodes of rectal bleeding v. Associated with Osier-Weber-Rendu syndrome and the CREST syndrome vi. Treatment: surgical resection d. Melanosis coli i. Common with laxative abuse ii. Gross: black pigmentation of the colon iii. Can mimic colitis or malignancy e. Pseudomembranous colitis (antibiotic-associated colitis)

i. Definition: acute colitis characterized by the formation of inflammatory pseudomembranes in the intestines ii. Organism: Clostridium difficile iii. Often brought on by a course of broad-spectrum antibiotics (especially clindamycin and ampicillin)

iv. Presentation: diarrhea, fever, and abdominal cramps v. Gross: yellow-tan mucosal membranes vi. Micro:

• Superficial colonic necrosis with an overlying pseudomembrane

• Pseudomembranes are mushroom-shaped inflammatory exudates composed of neutrophils, mucin, fibrin, and necrotic cellular debris vii. Diagnosis: detection of C. difficile toxin in the stool viii. Treatment: vancomycin or metronidazole

5. Diverticula a. Meckel diverticulum i. Definition: congenital small bowel diverticulum ii. Remnant of the vitelline (omphalomesenteric) duct iii. "Rule of 2s"

• 2% of the normal population

■ 2 feet from the ileocecal valve

• 2 years old or younger at the time of diagnosis

■ 2% of carcinoid tumors occur in a Meckel diverticulum iv. Presentation

■ Most are asymptomatic

• May contain rests of ectopic gastric mucosa and present with intestinal bleeding b. Colonic diverticulosis i. Definition: acquired outpouching of the bowel wall, characterized by herniation of the mucosa and submucosa through the muscularis propria ii. Epidemiology

• Extremely common in the United States

• Incidence increases with age iii. Risk factor: low-fiber diet leads to increased intraluminal pressure iv. Location: most common in the sigmoid colon v. Presentation

• Often asymptomatic

• Constipation alternating with diarrhea

• Left lower quadrant abdominal cramping and discomfort

• Occult bleeding and an iron deficiency anemia

■ Lower GI hemorrhage vi. Complications

Diverticulitis

• Perforation and peritonitis

6. Neoplasia a. Adenomatous colonic polyps i. Definition: benign neoplasm of the colonic mucosa that has the potential to progress to colonic adenocarcinoma ii. Presentation

• Commonly asymptomatic

■ Occult bleeding and iron deficiency anemia iii. Prognostic features

■ Tubular versus villous histology

Note

Given that only two layers of the bowel wall are involved, these acquired outpouchings are technically pseudodiverticula.

Clinical Correlate

It is estimated to take roughly 10 years to progress from adenoma to carcinoma, which makes colonoscopy an effective tool for identifying and removing adenomas before they progress to an invasive malignancy.

KflPUN^.

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• Pedunculated versus sessile appearance

• Degree of dysplasia iv. Diagnosis

• Hemoccult positive stools

■ Endoscopy b. Familial adenomatous polyposis (FAP)

i. Synonym: adenomatous polyposis coli (APC)

ii. Genetics

■ Autosomal dominant

• APC gene on chromosome 5q21

iii. Develop thousands of colonic adenomatous polyps iv. Diagnosis: discovery of more than 100 adenomatous polyps on endoscopy v. Complication: by age 40, virtually 100% will develop an invasive adenocarcinoma.

c. Gardner syndrome i. Autosomal dominant ii. Variant of FAP characterized by

• Numerous colonic adenomatous polyps

• Multiple osteomas

• Fibromatosis

• Epidermal inclusion cysts d. Turcot syndrome i. Rare variant of FAP characterized by

• Numerous colonic adenomatous polyps

e. Hereditary nonpolyposis colorectal cancer (HNPCC)

i. Synonym: Lynch syndrome ii. Genetics

■ Autosomal dominant

• Mutation of DNA nucleotide mismatch repair gene iii. Colon cancer iv. Increased risk of endometrial and ovarian carcinoma f. Peutz-Jeghers syndrome i. Autosomal dominant ii. Multiple hamartomatous polyps (primarily in the small intestine)

iii. Melanin pigmentation of the oral mucosa iv. Increased risk of cancer of the lung, pancreas, breast, and uterus g. Colonic adenocarcinoma i. Third most common tumor in terms of incidence and mortality in the United States ii. Risk factors

■ Diet low in fruits and vegetables

■ High red meat and animal fat consumption *. Adenomatous polyps

• Hereditary polyposis syndromes

■ Lynch syndrome

■ Ulcerative colitis iii. Genetics

Multiple mutations are involved

Table 15-2. Right-Sided Cancer Versus Left-Sided Cancer

j

Right-Sided Cancer

Left-Sided Cancer

' Gross

Polypoid mass

Circumferential growth producing a "napkin-

ring" con figuration !

Barium studies

Polypoid mass

"Apple core" lesion

Presentation

Bleeding

Change in bowel habits

• Occult blood in stool ■ Iron deficiency anemia

• Constipation or diarrhea

• Reduced caliber stools ■ Obstruction

iv. Diagnosis

■ Hemoccult positive stool

• Endoscopy with biopsy v. Pattern of spread

• Lymphatic spread to mesenteric lymph nodes

• Distant spread to liver, lungs, and bone vi. Staging: modified Dukes' (Astler-Coller) staging system vii. Treatment

• Surgical resection

Chemotherapy for metastatic disease

• Monitor CEA levels

Table J 5-3. The Modified Dukes' Staging System

Stage

Extent of Disease

A

Limited to the mucosa and submucosa

B1

Invasion into but not through the muscularis propria

B2

Invasion through the muscularis propria

invasion into but not through die muscularis propria

invasion through the muscularis propria

D

Distant metastasis

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h. Carcinoid tumors i. Neuroendocrine tumor often producing serotonin ii. Locations: appendix (most common) and terminal ileum iii. Metastasis to the liver may result in carcinoid heart disease iv. Carcinoid syndrome

• Cutaneous flushing

• Broncho spasm and wheezing

■ Fibrosis v. Diagnosis: urinary 5-H1AA (5-hydroxyindoleacetic acid)

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