6. Gastrointestinal Tract

Question 1

Diseases of teeth and supporting structures

Answer 1

• Caries is the most common cause of tooth loss in individuals younger than 35 years of age. The primary cause is destruction of tooth structure by acid end products of sugar fermentation by bacteria.
• Gingivitis is a common and reversible inflammation of the mucosa surrounding the teeth. It is associated with buildup of dental plaque and calculus.
• Periodontitis is a chronic inflammatory condition that can lead to the destruction of the supporting structures of the teeth with eventual loss of dentition. It is associated with poor oral hygiene and altered oral microbiota.

Question 2

Oral inflammatory lesions

Answer 2

• Aphthous ulcers are painful superficial ulcers of unknown etiology that may in some cases be associated with systemic diseases.
• Herpes simplex virus causes a self-limited infection that presents with vesicles (cold sores, fever blisters) that rupture and heal, without scarring, and often leave latent virus in nerve ganglia. Reactivation can occur.
• Oral candidiasis may occur when the oral microbiota is altered (e.g., after antibiotic use). Invasive disease may occur in immunosuppressed individuals.

Question 3

Lesions of the oral cavity

Answer 3

• Fibromas and pyogenic granulomas are common reactive lesions of the oral mucosa.
• Leukoplakia and erythroplakia are mucosal plaques that may undergo malignant transformation.
• The risk of malignant transformation is greater in erythroplakia (relative to leukoplakia).
• A majority of oral cavity cancers are squamous cell carcinomas.
• Oral squamous cell carcinomas are classically linked to tobacco and alcohol use, but the incidence of HPV-associated lesions is rising.

Question 4

Diseases of salivary glands

Answer 4

• Sialadenitis (inflammation of the salivary glands) can be caused by trauma infection (such as mumps), or an autoimmune reaction.
• Pleomorphic adenoma is a slow-growing neoplasm composed of a heterogeneous mixture of epithelial and mesenchymal cells. It is typically benign.
• Mucoepidermoid carcinoma is a malignant neoplasm of variable biologic aggressiveness that is composed of a mixture of squamous and mucous cells.

Question 5

Odontogenic cysts and tumors

Answer 5

• The jaws are a common site of epithelium-lined cysts derived from odontogenic remnants.
• The odontogenic keratocyst is locally aggressive, with a high recurrence rate.
• The periapical cyst is a reactive, inflammatory lesion associated with caries or dental trauma.
• The most common odontogenic tumors are ameloblastoma and odontoma.

Question 6

Diseases of the esophagus

Answer 6

• Esophageal obstruction may occur as a result of mechanical or functional anomalies. Mechanical causes include developmental defects, fibrotic strictures, and tumors.
• Achalasia, characterized by incomplete LES relaxation, increased LES tone, and esophageal aperistalsis, is a common form of functional esophageal obstruction.
• Esophagitis can result from chemical or infectious mucosal injury. Infections are most frequent in immunocompromised individuals.
• The most common cause of esophagitis is gastroesophageal reflux disease (GERD), which must be differentiated from eosinophilic esophagitis.
• Barrett esophagus, which may develop in patients with chronic GERD, is associated with increased risk for development of esophageal adenocarcinoma.
• Esophageal squamous cell carcinoma is associated with alcohol and tobacco use, poverty, caustic esophageal injury, achalasia, tylosis, and Plummer-Vinson syndrome.

Question 7

Acute and chronic gastritis

Answer 7

• Gastritis is a mucosal inflammatory process. When inflammatory cells are absent or rare, the term gastropathy can be applied.
• The spectrum of acute gastritis ranges from asymptomatic diseases to mild epigastric pain, nausea, and vomiting. Causative factors include any agent or disease that interferes with gastric mucosal protection. Acute gastritis can progress to gastric ulceration.
• The most common cause of chronic gastritis is H. pylori infection; most remaining cases are caused by NSAID,s, alcohol, or autoimmune gastritis.
• H. pylori gastritis typically affects the antrum and is associated with increased gastric acid production.
• H. pylori gastritis induces mucosa-associated lymphoid tissue (MALT) that can give rise to B-cell lymphomas (MALTomas).
• Autoimmune gastritis causes atrophy of the gastric body oxyntic glands, which results in decreased gastric acid production, antral G-cell hyperplasia, achlorhydria, and vitamin B12 deficiency. Anti-parietal cell and anti-intrinsic factor antibodies are typically present.
• Intestinal metaplasia develops in both forms of chronic gastritis and is a risk factor for development of gastric dysplasia and adenocarcinoma.
• Peptic ulcer disease can be caused by H. pylori chronic gastritis and the resultant hyperchlorhydria or NSAID use. Ulcers can develop in the stomach or duodenum and usually heal after suppression of gastric acid production, discontinuation of NSAID use, or, if present, H. pylori eradication.

Question 8

Gastric polyps and tumors

Answer 8

• Inflammatory and hyperplastic gastric polyps are reactive lesions associated with chronic gastritis. Risk for development of dysplasia increases with polyp size.
• Gastric adenomas develop in a background of chronic gastritis and are particularly associated with intestinal metaplasia and mucosal (glandular) atrophy. Adenocarcinoma frequently arises in gastric adenomas, which therefore require complete excision and surveillance to detect recurrence.
• Gastric adenocarcinomas are classified according to location and gross histologic morphology. Those with an intestinal histologic pattern tend to form bulky tumors and may be ulcerated, whereas those composed of mucus-filled signet ring cells typically display a diffuse infiltrative growth pattern that may thicken the gastric wall (linitis plastica) without forming a discrete mass.
• H. pylori infection is the most common etiologic agent for gastric adenocarcinoma, but other associations, including chronic atrophic gastritis and EBV infection, suggest several possible pathways of neoplastic transformation.
• Primary gastric lymphomas most often are derived from the mucosa-associated lymphoid tissue whose development is induced by chronic gastritis.
• Low- or intermediate-grade neuroendocrine (carcinoid) tumors arise from the diffuse components of the endocrine system and are most common in the gastrointestinal tract, particularly the small intestine. Tumors of the small intestine tend to be most aggressive while those of the appendix are almost always benign.
• Gastrointestinal stromal tumor (GIST), the most common mesenchymal tumor of the abdomen, occurs most often in the stomach. GISTs arise from benign pacemaker cells, also known as the interstitial cells of Cajal. A majority of tumors have activating mutations in either the c-KIT or the PDGFRA tyrosine kinases and respond to kinase inhibitors.

Question 9

Intestinal obstruction

Answer 9

• Intussusception is the most common cause of the intestinal obstruction in children younger than 2 years of age and can usually be treated by barium enema or air enema.
• Hirschprung disease is the result of defective neural crest cell migration from cecum to rectum. It gives rise to functional obstruction.
• Abdominal herniation may occur through any weakness or defect in the wall of the peritoneal cavity, including inguinal and femoral canals, umbilicus, and sites of surgical scarring.

Question 10

Vascular disorders of bowel

Answer 10

• Intestinal ischemia can occur as a result of either arterial or venous obstruction.
• Ischemic bowel disease resulting from hypoperfusion is most common at the splenic flexure, sigmoid colon, and rectum; these are watershed zones where two arterial circulations terminate.
• Systemic vasculitides and infectious diseases (e.g., CMV infection) can cause vascular disease that is not confined to the gastrointestinal tract.
• Angiodysplasia is a common cause of lower gastrointestinal bleeding in older adults.
• Hemorrhoids are collateral vessels that form in response to venous hypertension.

Question 11

Malabsorptive diarrhea

Answer 11

• Diarrhea can be characterized as secretory osmotic malabsorptive, or exudative.
• The malabsorption associated with cystic fibrosis is the result of pancreatic insufficiency (i.e., inadequate pancreatic digestive enzymes) and deficient luminal breakdown of nutrients.
• Celiac disease is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains. The malabsorptive diarrhea in celiac disease is due to loss of brush border surface area and possibly, deficient enterocyte maturation.
• Lactase deficiency causes an osmotic diarrhea owing to the inability to break down or absorb lactose.
• Abetalipoproteinemia is characterized by an inability to secrete triglyceride-rich lipoproteins due to an inherited transepithelial transport defect.
• The two forms of microscopic colitis, collagenous colitis and lymphatic colitis, both cause chronic watery diarrhea. The intestines are grossly normal, and the diseases are identified by their histologic features.

Question 12

Infectious enterocolitis

Answer 12

• Vibrio cholerae secretes a preformed toxin that causes massive chloride secretion. Water follows the resulting osmotic gradient, leading to secretory diarrhea.
• Campylobacter jujuni is the most common bacterial enteric pathogen in developed countries and also causes traveler’s diarrhea. Most isolates are noninvasive. Salmonella and Shigella spp. are invasive and associated with exudative bloody diarrhea (dysentery). Salmonella infection is a common cause of food poisoning. S. typhi can cause systemic disease (typhoid fever).
• Pseudomembranous colitis is often triggered by antibiotic therapy that disrupts the normal microbiota and allows C. difficile to colonize and grow. The organism produces toxins that disrupt epithelial function. Fecal microbial transplantation is becoming more common as a therapeutic approach in individuals with recurrent disease.
• Rotavirus is the most common cause of severe childhood diarrhea and diarrheal mortality worldwide. The diarrhea is secondary to loss of mature enterocytes, resulting in malabsorption as well as secretion.
• Parasitic and protozoal infections affect over half of the world’s population on a chronic or recurrent basis.

Question 13

Inflammatory bowel disease

Answer 13

• Inflammatory bowel disease (IBD) is an umbrella term for Crohn disease and ulcerative colitis.
• Crohn disease most commonly affects the terminal ileum and cecum, but any site within the gastrointestinal tract can be involved; skip lesions and noncaseating granulomas are common.
• Ulcerative colitis is limited to the colon, is continuous from the rectum, and ranges in extent from only rectal disease to pancolitis; neither skip lesions nor granulomas are present.
• Both Crohn disease and ulcerative colitis can have extraintestinal manifestations.
• IBD is thought to arise from a combination of alterations in host interactions with intestinal microbiota, intestinal epithelial dysfunction, and aberrant mucosal immune response.
• The risk for development of colonic epithelial dysplasia and adenocarcinoma is increased in patients who have had colonic IBD for more than 8 to 10 years.

Question 14

Colonic polyps, adenomas, and adenocarcinomas

Answer 14

• Intestinal polyps can be classified as nonneoplastic or neoplastic. The nonneoplastic polyps can be further defined as inflammatory, hamartomatous, or hyperplastic.
• Inflammatory polyps form as a result of chronic cycles of injury and healing.
• Hamartomatous polyps occur sporadically or as a part of genetic diseases. In the latter case, they often are associated with increased risk for malignancy.
• Hyperplastic polyps are benign epithelial proliferations most commonly found in the left colon and rectum. They are not reactive in origin, in contrast with gastric hyperplastic polyps; have no malignant potential; and must be distinguished from sessile serrated adenomas or polyps.
• Benign epithelial neoplastic polyps of the colon are termed adenomas. The hallmark feature of these lesions, which are the precursors of colonic adenocarcinomas, is cytologic dysplasia.
• In contrast with traditional adenomas, sessile serrated adenomas, or polyps, lack cytologic dysplasia and share some morphologic features with hyperplastic polyps.
• Familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) are the most common forms of familial colon cancer. FAP is caused by APC mutations, and patients typically have over 100 adenomas and develop colon cancer before 30 years of age.
• HNPCC is caused by mutations in DNA mismatch repair genes. Patients with HNPCC have far fewer polyps and develop cancer at an older age than that typical for patients with FAP but at a younger age than in patients with sporadic colon cancer.
• The vast majority of colonic cancers are adenocarcinomas. they arise either by APC-B-catenin pathway or the microsatellite instability pathway. The tow most important prognostic factors are depth of invasion and the presence or absence of metastases to lymph nodes or distant organs.

Question 15

Appendix

Answer 15

• Acute appendicitis is most common in children and adolescents. It is thought to be initiated by increased intraluminal pressure consequent to obstruction of the appendiceal lumen, which compromises venous outflow.
• The most common tumor of the appendix, the carcinoid, or well-differentiated neuroendocrine tumor, is most often discovered incidentally and is almost always benign.
• The clinical presentation of appendiceal adenocarcinoma can be indistinguishable from that of acute appendicitis, although the former tends to present in older patients.