General Pathology 601 for Dental Students

Pathology of The Small and Large Intestines

Melissa J. Contos, MD
Surgical Pathology/Cytopathology
Gateway Bldg, 6th floor
Office: (804) 828-9739
mjcontos@vcu.edu

Objectives | Development Anomalies | Ischemic Bowel Disease | Diarrhea and Dysentery Malabsorption | Idiopathic Inflammatory Bowel Disease | Diverticulosis | Tumors 

Objectives
Upon completion of this lecture you will be able to:

1. Define Meckel's diverticulum and Hirschsprung's disease and identify their pathologic processes.
2. Correlate the different pathogenic mechanisms for the development of diarrhea with histologic/laboratory findings.
3. Recognize the importance of antibiotics in initiation of clostridium difficile colitis (pseudomembranous colitis).
4. Explain the pathogenesis of celiac sprue.
5. Differentiate Crohn's disease from ulcerative colitis.
6. Describe the precursor lesion in colonic carcinoma.
7. Name the cell of origin and the most common location of carcinoid tumors.

Development Anomalies

Meckel's Diverticulum

• Common (2% of population)

• Usually asymptomatic (95%)

• True (all layers present) diverticulum--derived from failure of involution of the omphalomesenteric duct

• Located around 2 feet from the ileocecal valve on the antimesenteric border

Hirschsprung's Disease

• Failure of caudal migration of neural crest cells results in a segment of aganglionic bowel beginning at the anus

• There is functional obstruction and progressive distention of the colon proximal to the affected segment

• Males predominate 4:1 and there is an association with other congenital anomalies

Diarrhea and Dysentery (low volume/blood/pain)

Types

1. Secretory--persists during fasting

2. Osmotic--abates with fasting

3. Dysenteric--mucosal damage resulting in purulent bloody stools

4. Malabsorption--bulky stools from unabsorbed nutrients and fat

Pathogenesis

1. Infectious (i.e., enterocolitis)--half of deaths worldwide in children under 5

2. Viral (i.e., rotavirus--osmotic and secretory)--destruction of absorptive cells with preservation of crypt secretory cells

3. Bacterial--

• Cholera (also some stains of E. coli)--toxigenic-elaborate an enterotoxin (secretory)

• Salmonella (invasive)--lymphoid inflammation

• Shigella (invasive)--predominantly left side colon (mimics Ulcerative colitis in its distribution)

• Clostridium difficile--cytotoxic strains emerge after antibiotic use. Develop pseudomembranes consisting of fibrinopurulent debris and mucus

• TB

Malabsorption

Celiac sprue (gluten sensitive enteropathy)--genetic predisposition:

• Sensitivity to gluten that contains gliadin

• B lymphocytes accumulate in small intestinal lamina propria

• T lymphocytes invade the surface epithelial cells after exposure to gluten resulting in destruction of the surface enterocyte

• The crypt epithelium attempts to restore the normal architecture, but, once the proliferative rate is exceeded, the surface becomes flat (300X less surface area)

• Increased risk of long term malignant disease especially T-cell lymphomas

• Increased risk of gastrointestinal and breast carcinoma

Idiopathic Inflammatory Bowel Disease

Ulcerative Colitis

• Begins in rectum and proceeds proximally in continuity

• Approximately half of the cases limited to the left colon

• Inflammation limited to the mucosa, pseudopolyps common

• Greater risk of dysplasia and adenocarcinoma than Crohn's

• Association with primary sclerosing cholangitis

Crohn's

• Involves any area of the gastrointestinal tract--terminal ileum most common

• Transmural inflammation with fissure and fistula formation

• Skip areas

• Granulomas

• Risk of carcinoma less than ulcerative colitis

Diverticulosis

• Acquired (false) diverticula most common in sigmoid colon (false - mucosa and submucosa compose diverticula)

• Occurs in 50% of Western population over age 60 years

• Low fiber diets with small bulk require increased luminal pressure for propulsion of stool

• The increased pressure forces mucosa through weak areas in the wall (where vessels perforate the muscle alongside the taeniae)

• Most cases are asymptomatic but cramping pain, bleeding, and perforation occur

Tumors

Polyps (epithelial)

Adenomas

• Dysplastic precursors to adenocarcinoma

• 40-50% prevalence after age 60

• Familial predisposition to sporadic adenomas

• Risk of carcinoma dependent mostly on size

• Familial Polyposis Syndromes

  • Familial adenomatous polyposis (FAP)-5q21--mutation of APC tumor suppressor gene which encodes a protein believed to be important in cell adhesion; autosomal dominant

  • Hereditary nonpolyposis colorectal cancer (HNPCC)--Inherited mutation to a DNA repair gene; i ncreased risk other cancer, endometrial

Carcinoma (figure 15-36 illustrates multi-hit concept of pathogenesis) 

• Right sided cancers tend to grow as exophytic masses, fatigue, weakness iron deficiency anemia, no obstruction

• Left sided cancers tend to be annular, napkin ring lesions, obstruction occurs as well as accult bleeding, change in bowel habit

• Most important prognostic feature is extent of tumor at the time of diagnosis!

• Staging system used here is TNM where:

  • T stands for depth of invasion of tumor into bowel wall

  • N is nodal metastasis

  • M is distant metastasis (most often liver followed by lungs)

• Often secrete carcinoembryonic antigen (CEA) which can be used to evaluate recurrence or metastatic disease.

Carcinoid

• Neuroendocrine, derived from epithelial stem cells, that produce bioactive compounds which play a role in coordinating gut function

• Most common site is appendix

• Carcinoid syndrome (described in table 15-13)--can only occur in GI carcinoids if the liver is bypassed, such as is present in hepatic metastasis

Digital Legends for Labs
Lab 1 | Lab 2 | Lab 3 | Lab 4 | Lab 5 | Lab 6 | Lab 6b | Lab 7 | Lab 8 | Lab 9 | Lab 9b | Lab10 | Lab 10b | Lab11 | Lab 12 |
Lab 13 | Lab 14 | Lab 15 | Lab 15b | Lab 16 | Lab 16b | Lab 17 | Lab 18

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Updated September 5, 2007