Pbl Exam 9 Case 2-2

Front 1

1. What is pancreatic heterotopia?

Back 1

With pancreatic heterotopia, nodules of essentially normal pancreatic tissue up to 1 cm in diameter may be present in the gastric submucosa, muscle wall, or at a subserosal location.

When in the pylorus, localized inflammation may lead to pyloric obstruction.

Front 2

2. What is gastric heterotopia?

Back 2

With gastric heterotopia, small patches of ectopic gastric mucosa in the duodenum or in more distal sites may present as perplexing sources of bleeding, due to peptic ulceration of adjacent mucosa.

Front 3

3. What is a diaphragmatic hernia?

Back 3

Defective closure of the diaphragm leads to weakness or partial to total absence of a region of the diaphragm, usually on the left. Resultant herniation of abdominal contents into the thorax in utero produces a diaphragmatic hernia.

Usually, the stomach or a portion of it insinuates into the pouch, but occasionally small bowel and even a portion of the liver accompany it. The herniation may be asymptomatic or may engender potentially lethal respiratory problems in the newborn.

Front 4

4. What is congenital hypertrophic pyloric stenosis?

Back 4

This is encountered in infants as a disorder that affects males 3-4x more than females. Pyloric stenosis may also occur in association with Turner syndrome, trisomy 18, and esophageal atresia.

Regurgitation and persistent, projectile, nonbilious vomiting usually appear in the second or third week of life.

Physical exam reveals visible peristalsis and a firm, ovoid palpable mass in the region of the pylorus or distal stomach, the result of hypertrophy and possibly hyperplasia of the muscularis propria of the pylorus. Edema and inflammatory changes in the mucosa and submucosa may aggravate the narrowing. Surgical muscle splitting is curative.

Front 5

5. What is acquired pyloric stenosis?

Back 5

This occurs in adults and is one of the long term risks of gastritis or peptic ulcers close to the pylorus.

Carcinomas of the pyloric region, lymphomas, or adjacent carcinomas of the pancreas are more ominous causes.

In these cases, inflammatory fibrosis or malignant infiltration narrow the pyloric channel, producing pyloric outlet obstruction. In rare instances, hypertrophic pyloric stenosis is the result of prolonged pyloric spasm.

Front 6

6. What does gastritis mean?

Back 6

Gastritis is simply defined as inflammation of the gastric mucosa. It is a histologic diagnosis.

Inflammation may be predominantly acute, w/neutrophilic infiltration; or it can be chronic, w/lymphocytes and/or plasma cells predominating and associated intestinal metaplasia and atrophy.

Front 7

7. What is acute gastritis?

Back 7

Acute gastritis is an acute mucosal inflammatory process, usually of transient nature.

The inflammation may be accompanied by hemorrhage into the mucosa and, in more severe circumstances, by sloughing of the superficial mucosa (mucosal erosion). This severe erosive form of the disease is an important cause of acute GI bleeding.

Front 8

8. Acute gastritis is usually associated with what 12 things...?

Back 8

1. Heavy use of NSAIDs
2. Excessive EtOH consumption
3. Heavy smoking
4. Treatment w/chemo
5. Uremia
6. Systemic bacterial or viral infections
7. Severe stress
8. Ischemia and shock
9. Suicidal attempts, as w/acids and alkali
10. Gastric irradiation or freezing
11. Mechanical trauma (e.g. nasogastric tubing)
12. Distal gastrectomy

Front 9

9. What is the pathogenesis of acute gastritis?

Back 9

One more of the following influences are thought to be operative in these varied settings:
1. Increased acid secretion w/back diffusion
2. Decreased production of bicarb buffer
3. Reduced blood flow
4. Disruption of the adherent mucus layer
5. Direct damage to the epithleium

*Mucosal insults can act synergistically.

Front 10

10. What is the morphology of acute gastritis?

1/2

Back 10

In the mildest form, the lamina propria exhibts only moderate edema and slight vascular congestion. The presence of neutrophils above the basement membrane (w/in the epithelial space) is abnormal and signifies active inflammation ("activity").

With more severe mucosal damage, erosion and hemorrhage develop.

Front 11

11. What is the morphology of acute gastritis?

2/2

Back 11

Erosion denotes loss of the superficial epithelium, generating a defect in the mucosa that does not cross the muscularis mucosa. It is accompanied by a robust acute inflammatory infiltrate and extrusion of a fibrin containing purulent exudate into the lumen.

Hemorrhage may occur independently, generating punctate dark spots in an otherwise hyperemic mucosa or in association w/erosion.

Concurrent erosion and hemorrhage is termed *acute erosive hemorrhagic gastritis. Large areas of the gastric mucosa may be denuded, but the involvement is superficial and rarely affects the entire depth of the mucosa.

Front 12

12. What are the clinical features of acute gastritis?

Back 12

Depending on the severity, it may be entirely asymptomatic, or it may cause variable epigastric pain, nausea, and vomiting; or it may present w/overt hemorrhage, massive hematemesis, melena, and potentially fatal blood loss.

Overall, it is one of the major causes of massive hematemesis, as in alcoholics. In particular settings, the condition is quite common. As many as 25% of persons who take daily aspirin develop acute gastritis, many with bleeding.

Front 13

13. What is chronic gastritis?

Back 13

Chronic gastritis is defined as the presence of chronic mucosal inflammatory changes leading eventually to mucosal atrophy and intestinal metaplasia, usually in the absence of erosions.

The epithelial changes may become dysplastic and constitute a background for the development of carcinoma.

Front 14

14. What are the major etiologic assocations of chronic gastritis?

8 of them...

Back 14

1. Chronic infection by H. pylori
2. Immunologic (autoimmune) in association w/pernicious anemia
3. Toxic, as with alcohol and cigarette smoking
4. Postsurgical, esp following antrectomy w/gastroenterostomy w/reflux of bilious duodenal secretions
5. Motor and mechanical, including obstruction, bezoars (luminal concretions), and gastric atony
6. Radiation
7. Granulomatous conditions (Crohns disease)
8. Misc - amyloidosis, graft-vs-host disease, uremia

Front 15

15. How is H. pylori associated w/chronic gastritis?

How is it Dx?

Back 15

H. pylori colonizes more than 50% of Americans over age 50. It is an S-shaped gram-negative rod present in 90% of patients w/chronic antral gastritis.

H. pylori can be Dx by antibody serologic test, breath test, bacterial culture, direct bacterial visualization in gastric biopsy, ulcer disease, gastric adenocarcinoma, and gastric lymphoma.

Front 16

16. What are the four traits of H. pylori that allow it to flourish in the stomach?

Back 16

1. Motility (via flagella), allowing it to swim through viscous mucus
2. Elaboration of a urease, which produces ammonia and carbon dioxide from endogenous urea, thereby buffering gastric acid in the immediate vicinity of the organism
3. Expression of bacterial adhesins, such as BabA, which binds to the fucosylated Lewis B blood-group antigens, enhances binding to blood group O antigen bearing cells
4. Expression of bacterial toxins, such as cytotoxin associated gene A (CagA) and vacuolating cytotoxin gene A (VacA).

Front 17

17. What is autoimmune gastritis?

Back 17

This accounts for less than 10% of cases of chronic gastritis. It results from the presence of autoantibodies to components of gastric gland parietal cells, including antibodies against the acid producing enzyme H⁺K⁺-ATPase, gastrin receptor, and intrinsic factor.

Gland destruction and mucsal atrophy lead to loss of acid production. In the most severe cases, production of intrinsic factor is lost, leading to pernicious anemia.

This uncommon form of gastritis is seen in association w/other autoimmune disorders such as Hashimotos, Addison's, and DM type I. Patients w/autoimmune gastritis have a significant risk for developing gastric carcinoma and endocrine tumors (carcinoid tumors).

Front 18

18. What is the morphology of chronic gastritis?

Back 18

Grossly, chronic gastritis exhibits a reddened, boggy, coarse textured mucosa. The distribution depends on the etiology (autoimmune or H. pylori).

Histologically, an inflammatory infiltrate with lymphocytes and plasma cells is present in the lamina propria. Active inflammation is signified by the presence of neutrophils within the glandular and surface epithelial layer. Lymphoid aggregate, some with germinal centers, are frequently observed within the mucosa.

Front 19

19. What is the morphology of autoimmune gastritis?

Back 19

Autoimmune gastritis is characterized by diffuse mucosal damage of the body-fundic mucosa, with less intense to absent antral damage, probably due to the autoantibodies against parietal cells.

Front 20

20. What is the morphology of gastritis due to H. pylori?

Back 20

Infections with H. pylori tend to affect the antral mucosa or both antral and body-fundic mucosa. The mucosa is usually reddened and has a courser texture than normal.

The inflammatory infiltrate may create a mucosa with thickened rugal folds, mimicking early infiltrative lesions.

Front 21

21. What are the four additional histologic features characteristic of chronic gastritis?

Back 21

1. Regenerative change of surface columnar cells

2. Metaplasia of surface columnar epithelium to intestinal-type epithelium

3. Atrophy is evident by marked loss in glandular structures; atrophy is quite freq associated w/autoimmune gastritis and pangastritis caused by H. pylori

4. Dysplasia in some cases of long-standing chronic gastritis

Front 22

22. Where are the H. pylori organisms found in those infected?

Back 22

The organism lies in the superficial mucus layer and among the microvilli of epithelial cells. The distribution of organisms can be very patchy and irregular, with areas of heavy colonization adjacent to those with no organisms. In extreme cases, the organisms carpet the luminal surfaces of surface epithelial cells lining the gastric pits; they do not invade the mucosa.

Even in heavily colonized stomachs, the organisms are absent from areas with intestinal metaplasia. Conversely, organisms may be present in foci of pyloric metaplasia in an inflamed duodenum and in the gastric-type mucosa of Barrett esophagus.

Front 23

23. What are the clinical features of chronic gastritis?

Back 23

Chronic gastritis is usually asymptomatic, although nausea, vomiting, or upper abdominal discomfort can occur.

Individuals with advanced gastritis from H. pylori or other environmental causes are often hypochlorhydric, owing to parietal cell damage and atrophy of body and fundic mucosa. However, since parietal cells are never completely destroyed, these patients do not develop achlorhydria or pernicious anemia.

Serum gastrin levels are usually within the normal range or only modestly elevated.

Front 24

24. What happens with severe parietal cell loss in autoimmune gastritis?

Back 24

Hypochlorhydria or achlorhydria and hypergastrinemia are characteristically present.

Circulating autoantibodies to a diverse array of parietal cell antigens may be detected.

A small subset of these patients (10%) may develop overt pernicious anemia after a period of years.

Front 25

25. What is the relationship of chronic gastritis to the development of peptic ulcer disease and gastric carcinoma?

Back 25

Most patients with a peptic ulcer, whether duodenal or gastric, have H. pylori infection.

H. pylori is though to contribute to the pathogenesis of both gastric carcinoma and lymphoma.

The long term risk of gastric cancer in patients with autoimmune gastritis is 2-4% which is considerably greater than that of the normal population.

Front 26

26 What is esosinophilic gastritis?

Back 26

Eosinophilic gastritis is an idiopathic condition that features a prominent eosinophilic infiltrate of the mucosa, muscle wall, or all layers of the stomach, usually in the antral or pyloric region.

This disorder typically affects middle aged women, and the primary symptom is abdominal pain, although swelling of the pylorus may produce gastric outlet obstruction.

It may occur in association with eosinophilic enteritis and is often accompanied by a peripheral eosinophilia. Steroid therapy is usually effective.

Front 27

27. What is allergic gastroenteropathy?

Back 27

Allergic gastroenteropathy is a disorder of children that may produce symptoms of diarrhea, vomiting, and growth failure.

An infiltrate of eosinophils limited to the mucosa can usually be demonstrated in antral biopsies.

Front 28

28. What is lymphocytic gastritis?

Back 28

Lymphocytic gastritis is a condition in which lymphocytes densely populate the epithelial layer of the mucosal surface and gastric pits and suffuse the lamina propria. The intraepithelial lymphocytes are exclusively T lymphocytes, mostly CD8+ cells.

The gastritis is generally restricted to the body of the stomach. This condition produces indistinct symptoms such as abdominal pain, anorexia, nausea, and vomiting. Although idiopathic in nature, 45-60% of cases are associated w/celiac disease. Therefore, an immune-mediated pathogenesis is most likely.

Front 29

29. What is granulomatous gastritis?

Back 29

The presence of intramucosal epithelioid granulomas can usually be attributed to Crohns disease, sarcoidosis, infection (tuberculosis, histoplasmosis, anisakiasis), a systemic vasculitis, or as a reaction to foreign materials.

Granulomatous gastritis is the term reserved for patients w/o these concurrent conditions. This idiopathic disorder is clinically benign. The predominant pathologic finding is narrowing and rigidity of the gastric antrum due to transmural granulomatous inflammmation.

Front 30

30. What is graft-vs-host disease and how does it relate to gastritis?

Back 30

Gastritis associated w/ GVHD can be encountered in the setting of bone marrow transplantation.

Histologically, there is a relatively mild lymphocytic infiltrate in the lamina propria and apoptosis of glandular epithelial cells, in particular the mucous neck cells.

Front 31

31. What is reactive gastropathy?

Back 31

Reactive gastropathy is a group of disorders that exhibit characteristic mucosal histologic changes that may include: foveolar hyperplasia with loss of mucin and glandular regenerative changes, mucosal edema and dilation of mucosal capillaries, and smooth muscle fibers extending into the lamina propria between the glands.

*The key to the definition is the absence of active (neutrophilic) inflammation of the epithelium.

Histologically, the antral mucosa exhibits reactive gastropathy and dilated capillaries containing fibrin thrombi.

Front 32

32. What causes reactive gastropathy?

Back 32

Reactive gastropathy is fairly common. The etiology is related to chemical injury from COX inhibitors or bile reflex, and from mucosal trauma resulting from prolapse.

In particular, gastric antral trauma or prolapse induce a characteristic lesion referred to as gastric antral vascular ectasia.

Endoscopy shows longitudinal stripes of edematous erythematous mucosa alternating with less severely injured mucosa (water-melon stomach).

Front 33

33. What are ulcers?

Back 33

Ulcers are defined histologically as a breach in the mucosa of the alimentary tract that extends thru the muscularis mucosa into the submucosa or deeper.

Although they may occur anywhere in the GI tract, none are as prevalent as the peptic ulcers that occur in the duodenum and stomach.

Front 34

34. How are ulcers distinguished from erosions?

Back 34

Ulcers are to be distinguished from erosion, in which there is epithelial disruption within the mucosa BUT NO BREACH of the muscularis mucosa.

Front 35

35. What are peptic ulcers?

What is the prevalence?

Back 35

Peptic ulcers are chronic, most often solitary, lesions that occur in any portion of the GI tract exposed to the aggressive actions of acid/peptic juice.

Peptic ulcers are usually solitary lesions less than 4cm in diameter.

The lifetime incidence is 10% for men and 4% for women in the US, typically middle-aged and older.

Even with healing, however, the tendency to develop peptic ulcers remain, b/c of recurrent infections w/H. pylori.

Front 36

36. Where are peptic ulcers usually located?

Back 36

In order of decreasing frequency:

1. Duodenum, first portion
2. Stomach, usually antrum
3. At the gastroesophageal junction, in the setting of GERD or Barretts
4. W/in the margins of a gastrojejunostomy
5. In the duodenum, stomach, and/or jejunum of patients w/Zollinger-Ellison syndrome
6. W/in or adjacent to an ileal Meckel diverticulum that contains ectopic gastric mucosa

Front 37

37. What is the pathogenesis of peptic ulcers?

Back 37

Peptic ulcers are produced by an imbalance between gasttroduodenal mucosal defense mechanisms and the damaging forces, particularly gastric acid and pepsin.

Hyperacidity is not a prerequisite, however; rather, gastric ulceration occurs when mucosal defenses fail, as when mucosal blood supply drops, gastric emptying is delayed, or epithelial restitution is impaired.

Most peptic ulcers are associated w/H. pylori infections; it is present in 70% of gastric ulcers, and virtually all patients w/duodenal ulcers.

Front 38

38. What are the normal gastric defenses?

(four of them)

Back 38

1. Surface mucus and bicarb secretion
2. Apical epithelial cell transport systems
3. Mucosal blood flow sustaining mucosal integrity and epithelial regeneration
4. Prostaglandins

Front 39

39. How does H. pylori cause injury?

7 main reasons:

Back 39

1. Although H. pylori doesn't invade the tissues, it induces an intense inflammatory and immune response via increased IL-1, IL-6, TNF, and most notably, IL-8 (activates neutrophils).
2. Several bacterial gene products are involved in caused cell injury and induction of inflammation (H. pylori secretes urease that breaks down urea to form toxic compounds).
3. H. pylori enhances gastric acid secretion and impairs duodenal bicarb production (favors gastric metaplasia which is suitable for colonization).
4. Several H. pylori proteins are immunogenic, and they evoke a strong T and B cell response
5. Bacterial platelet-activating factor promotes capillary thrombosis and occlusion.
6. Other antigens including LPS's recruit inflammatory cells to the mucosa.
7. Mucosal damage permits nutrient leakage onto the surface environment, thus sustaining the bacillus in the mucus layer.

Front 40

40. What strain of H. pylori is most common?

Back 40

Over 80% of patients w/duodenal ulcers are infected by strains that are cytotoxin-associated antigen (CagA) positive.

This antigen is a marker for the Cag pathogenicity island, which encodes genes involved in the pro-inflammatory and tissue damaging effects of H. pylori.

Front 41

41. What is one of the more important genes that are regulated by CagA?

Back 41

The vacuolating toxin (VacA); the CagA gene is essential for the expression of this toxin.

This toxin causes cell injury (via vacuole formation).

It also behaves as a passive urea transporter thereby increasing the permeability of the epithelium to urea. Urea is then broken down into toxic intermediates by bacterial urease.

Front 42

42. What are some other promoters of gastric mucosal ulceration?

Back 42

1. Gastric hyperacidity: increased parietal cell mass from excess gastrin production (e.g. a gastrinoma), causing multiple peptic ulcerations (Zollinger-Ellison syndrome).
2. Chronic NSAID use, suppressing mucosal prostaglandin synthesis.
3. Cigarette smoking, alcoholic cirrhosis, corticosteroids, and hypercalcemia (e.g., chronic renal failure or hyperparathyroidism.
4. In some patients w/duodenal ulcers, there is too rapid gastric emptying, exposing the duodenal mucosa to an excessive acid load.
5. Personality and psychological stress can contribute.

Front 43

43. Where are peptic ulcers usually located?

Back 43

98% are located in the first portion of the duodenum or in the stomach.

Most duodenal ulcers are within a few cm's of the pyloric ring. The anterior wall of the duodenum is affected more often than the posterior wall.

Gastric ulcers are located along the lesser curvature, in or around the border zone between the oxyntic mucosa and the antral mucosa. Less commonly, gastric ulcers may occur on the anterior or posterior walls, or along the greater curvature.

About 10-20% of patients may have both a duodenal and a gastric ulceration.

Front 44

44. What is the morphology of peptic ulcers?

Back 44

Small lesions (<0.3cm) are most likely to be shallow erosions; those over 0.6cm are likely to be ulcers.

The classic peptic ulcer is a round to oval, sharply punched-out defect w/relatively straight walls. The mucosal margin may overhang the base slightly, particularly on the upstream portion of the circumference. The margins are usually level w/the surrounding mucosa or only slightly elevated. Heaping-up of these margins is rare in the benign ulcer, but is characteristic of the malignant lesions.

Microscopically, there are thin superficial layers of necrotic debris with underlying inflammation merging into granulation tissue and deep scarring. The scarring may involve the entire thickness of the stomach, puckering of the surrounding mucosa creates mucosal folds that radiate from the crater in a spoke-like fashion. The surrounding mucosa usually exhibits chronic gastritis.

Front 45

45. What are the four zones in active ulcers w/ongoing necrosis?

Back 45

1. The base and margins have a superficial thin layer of necrotic fibrinoid debris not visible to the naked eye.
2. Beneath this layer is a zone of nonspecific inflammatory infiltrate w/neutrophils predominating.
3. In the deeper layers, esp in the base of the ulcer, there is active granulation tissue infiltrated w/mononuclear leukocytes.
4. The granulation tissue rests on a more solid fibrous or collagenous scar. Vessel walls within the scarred area are typically thickened by the surrounding inflammation and are occasionally thrombosed.

Front 46

46. How are peptic ulcers distinguished from acute erosive gastritis or stress ulcers?

Back 46

Gastritis remains after the ulcer has healed in those w/peptic ulcers.

Recurrence of the ulcer does not appear to be related to progression of the gastritis. This feature is helpful in distinguishing peptic ulcers from acute erosive gastritis or stress ulcers, since the adjacent mucosa is generally normal in the latter two conditions.

Front 47

47. What are the clinical features of peptic ulcer disease?

Back 47

Epigastric gnawing, burning, or aching pain, worse at night and 1-3 hours after meals.

Nausea, vomiting, bloating, belching, and weight loss occur.

Complications include anemia, hemorrhage, perforation, and obstruction. Malignant transformation is rare and related to underlying gastritis.

Front 48

48. Where is the referred pain in peptic ulcers?

Back 48

With penetrating ulcers, the pain is occasionally referred to the back, the left upper quadrant, or chest.

This type of pain may be misinterpreted as being of cardiac origin.

Front 49

49. What is acute gastric ulceration?

Back 49

Acute gastric ulceration refers to focal, acute mucosal defects in the setting of severe stress (stress ulcer).

Stress erosions and ulcers are most commonly encountered in patients w/shock, extensive burns, sepsis, or severe trauma; in any intracranial injury that raises ICP; and following intracranial surgery.

Front 50

50. What are Curling ulcers?

Back 50

Acute gastric ulcerations occurring in the proximal duodenum and associated w/severe burns or trauma are called Curling ulcers.

Front 51

51. What are Cushing ulcers?

Back 51

Gastric, duodenal, and esophageal ulcers arising in patients w/intracranial injury, operations, or tumors are designated Cushing ulcers and carry a high incidence of perforation.

Front 52

52. What is the pathogenesis of acute gastric ulceration?

Back 52

NSAIDs may cause acute ulceration due to the decreased prostaglandin production from the inhibition of COX.

The pathogenesis is unclear, but may be related to impaired oxygenation, vagal stimulation, or systemic acidosis.

Front 53

53. Why would lesions associated with intracranial injury cause acute gastric ulceration?

Back 53

The direct stimulation of vagal nuclei by increased ICP leads to hypersecretion of gastric acid.

Front 54

54. What is the morphology of acute gastric ulcerations?

Back 54

Acute stress ulcers are usually less than 1cm and are circular and small. The ulcer base is freq stained a dark brown by the acid digestion of extruded blood.

The gastric rugal pattern is essentially normal and the margins and base of the ulcers are not indurated.

Microscopically, acute stress ulcers are abrupt lesions, with essentially unremarkable adjacent mucosa.

Front 55

55. What are the clinical features of acute gastric ulcerations?

Back 55

Acute gastric erosions or ulcers occur in 5-10% of ICU patients.

*The single most important determinant of clinical outcome is the ability to correct the underlying condition(s).

The gastric mucosa can recover completely if the patients do not succumb to their primary disease.

Front 56

56. What is gastric dilation?

Back 56

Gastric dilation can arise from gastric outlet obstruction (e.g. pyloric stenosis) or from the functional atony of the stomach and intestines (paralytic ileus) that may develop in patients with generalized peritonitis.

The stomach may contain as much as 10-15 L of fluid; it can rupture, causing shock followed by death if not treated immediately.

Front 57

57. What are phytobezoars?

Trichobezoars?

Back 57

Phytobezoars are derived from plant material, including fibers, leaves, roots, and skins of almost any plant matter.

Tichobezoars, AKA hairballs, consist of ingested hair w/in a mucoid coat containing decaying food-stuff.

The dysmotility following partial gastrectomy or partial gastric outlet obstruction is conducive to bezoar formation from more conventional ingested food.

Front 58

58. What is hypertrophic gastropathy?

Back 58

Hypertrophic gastropathy is a group of uncommon conditions, all characterized by giant cerebriform enlargement of the rugal folds of the gastric mucosa.

The rugal enlargement is caused by hyperplasia of the mucosal epithelial cells, without inflammation.

Front 59

59. What are the three variants of hypertrophic gastropathy?

Back 59

1. Ménétrier disease, resulting from profound hyperplasia of the surface mucous cells w/accompanying glandular atrophy.
2. Hypertrophic-hypersecretory gastropathy, associated w/hyperplasia of the parietal and chief cells within gastric glands.
3. Gastric gland hyperplasia secondary to excessive gastrin secretion, in the setting of gastrinom (Zollinger-Ellison syndrome).

Front 60

60. Why are the three conditions of hypertrophic gastropathy important?

Two reasons...

Back 60

1. They may mimic infiltrative carcinoma or lymphoma of the stomach on endoscopic and radiographic exams.

2. The enormous increase in acid secretions in hypertrophic-hypersecretory gastropathy and Zollinger-Ellison syndrome places patients at risk for peptic ulceration.

Front 61

61. What is the pathogenesis of Ménétrier disease?

Back 61

Ménétrier disease is most often encountered in the 4th-6th decade but is occasionally seen in children.

A role has been suggested for growth factor overexpression in superficial gastric epithelium. Transgenic mice w/transforming growth factor-α (TGF-α) expressed in the stomach exhibit a disorder similar to to human Ménétrier disease.

Although the disorder may be asymptomatic, it often produces epigastric discomfort, diarrhea, weight loss, and sometimes bleeding related to superficial rugal erosions.

Front 62

62. What is the morphology of Ménétrier disease?

Back 62

The hypertrophic change may predominantly involve the body-fundus or antrum or may affect the entire stomach. The gastric secretions contain excessive mucus and little to no HCl due to glandular atrophy.

In some patients, there may be sufficient protein loss in the gastric secretions to produce hypoalbuminemia and peripheral edema, thus constituting a from of protein-losing gastroenterpathy.

Infrequently, the mucosal hyperplasia becomes metplastic, providing a soil for the development of gastric carcinoma.

Front 63

63. What are gastric varices?

Back 63

Gastric varices develop in the setting of portal hypertension but less often than esophageal varices.

Most lie within 2-3 cm of the gastroesophageal junction, arising from longitudinally placed submucosal veins.

They appear as masslike nodular and tortuous winding elevations of the mucosa in the cardia or fundus. Due to their deep submucosal or subserosal location and the normal color of the overlying mucosa, it may be difficult to distinguish varices from enlarged rugae or even malignancy.

Front 64

64. What does the term "polyp" mean?

Back 64

In the GI tract, the term polyp is applied to any nodule or mass that projects above the level of the surrounding mucosa.

The mucsal polyps are classified as non-neoplastic or neoplastic. Gastric polyps are uncommon.

Front 65

65. What is the morphology of gastric polyps?

Back 65

Most gastric polyps (90%) are non-neoplastic and appear to be of a hyperplastic nature. They are composed of a variable mixture of hyperplastic surface epithelium (foveolar epithelium) and cystically dilated glandular tissue with a lamina propria containing increased inflammatory cells and smooth muscle.

Most hyperplastic polyps are small and sessile (w/o a stalk) and are commonly located in the antrum. They have epithelial tubules and cysts interspersed with an inflamed stroma. They are common in chronic gastritis, frequently multiple, and have no malignant potential per se.

Front 66

66. What is a gastric adenoma?

Back 66

The adenoma of the stomach constitutes 5-10% of the polypoid lesions in the stomach.

By definition, an adenoma contains proliferative dysplastic epithelium and thereby has malignant potential.
Adenomatous polyps are much more common in the colon.

Front 67

67. What is the morphology of a gastric adenoma?

Back 67

Gastric adenomas may be sessile (without a stalk) or pedunculated (stalked).

The most common location is the antrum; these lesions are usually single, and may grow up to 3-4 cm in size.

In contrast to the colon, adenomatous change in the stomach may cover a large regions of flat gastric mucosa without forming a mass lesion.

Front 68

68. What are fundic gland polyps?

What gene mutations are associated w/these polyps?

Back 68

The fundic gland polyp is an innocuous cystic dilation of glands in the oxyntic mucosa. These polyps usually occur sporadically, but they can occur in the syndrome of familial adenomatous polyposis.

Sporadic fundic gland polyps also exhibit mutations in β-catenin with high frequency.

Front 69

69. What are hamartomatous polyps?

Back 69

The hamartomatous polyps may occur in isolation, but gastric Puetz-Jeghers polyps are most commonly seen as part of the Peutz-Jeghers syndrome, and gastric juvenile polyps as part of the juvenile polyposis syndrome.

Front 70

70. What is an inflammatory fibroid polyp (eosinophilic granuloma)?

Back 70

The inflammatory fibroid polyp is a strikin lesion that is a bulky submucusal growth composed of inflamed vascularized fibromuscular tissue w/a prominent eosinophilic infiltrate and a tenuous mucosa stretched over the surface.

These polyps may occur anywhere in the GI tract but are found most freq in the distal stomach. As they protrude into the lumen, they may occlude the pyloric channel and present abruptly as acute gastric outlet obstruction. Their origin is unknown.

Front 71

71. What are the clinical features of hyperplastic polyps and gastric adenomas?

Back 71

Hyperplastic polyps are seen most freq in the setting of chronic gastritis. They are regarded as having no malignant potential but are nevertheless found in about 20% of stomachs resected for carcinoma.

The incidence of gastric adenomas increases with age. Up to 40% of gastric adenomas contain a focus of carcinoma at the time of Dx. Unlike colonic adenomas which usually arise from apparently normal mucosa, the usual substratum for gastric adenomas is chronic gastritis with intestinal metaplasia. Autoimmune gastritis can also lead to gastric adenoma formation.

Front 72

72. What is prevalence of gastric carcinoma?

Back 72

Of gastric malignancies, 90-95% are carcinoma (v.s lymphomas, carcinoids, or spindle cell tumors). Gastric carcinoma is the second most common tumor in the world.

Worldwide distribution is widely variable; US incidence has decreased 4x over the last 60 years.

Prognosis is dismal, with 5-year survival rates of 20%. It represents 2.5% of US cancer deaths.

Front 73

73. What are the two Laurén classifications of gastric carcinomas?

Back 73

1. Those exhibiting an intestinal morphology with the formation of bulky tumors composed of glandular structures. This type predominates in high risk areas, and develops from precursor lesions. It has a mean age of incidence of 55 years and a M:F ratio of 2:1.

2. Those with diffuse, infiltrative growth of poorly differentiated discohesive malignant cells. This type is relatively constant, and the tumors have no identifiable precursor lesions. Diffuse gastric cancer occurs in slightly younger patients, with an approx equal M:F ratio.

Front 74

74. What is the pathogenesis of gastric carcinomas?

Back 74

Environment

Diet: lack of regrigeration, use of preservatives, lack of fresh fruit and veggies

Cigarette smoking increases risk 1.5-3x

Host: infection by H. pylori with chronic gastritis; autoimmune gastritis; partial gastrectomy permitting gastroduodenal reflux.

Front 75

75. What genetic factors play a role in gastric carcinoma?

Back 75

Gastric mucosa dysplasia is a common result with genetic instability in DNA repair genes, telomerase expression, and c-met, K-sam and c-ERB-B2 abnormalities (growth factor receptor pathways).

Also, allelic losses in various chromosomal loci, and microsatellite instability in several genes including TFGβRII, BAX, and IGFRII.

Moreover, p53 mutations are present in a majority of tumors, and abnormalities in E-cadherin expression are quite frequent.

Front 76

76. What is the common location for gastric carcinomas?

Back 76

The location within the stomach is as follows: pylorus and antrum (50-60%); cardia (25%); with the remainder in the body and fundus.

The lesser curvature is involved in about 40% and the greater curvature in 12%.

Thus, a favored location is the lesser curvature of the antropyloric region.

Front 77

77. What is the morphological feature that has the greatest impact on clinical outcome?

Back 77

The depth of invasion.

Early gastric carcinoma is defined as a lesion confined to the mucosa and submucosa, regardless of the presence or absence of perigastric lymph node metastases.

Advanced gastric carcinoma is a neoplasm that has extended below the submucosa into the muscular wall.

Front 78

78. What are the three macroscopic growth patterns of gastric carcinoma?

Back 78

1. Exophytic, with protrusion of a tumor mass into the lumen

2. Flat or depressed, in which there is no obvious tumor mass within the mucosa

3. Excavated, whereby a shallow or deeply erosive crater is present in the wall of the stomach.

Front 79

79. How can erosive growth patterns of gastric carcinoma be distinguished from peptic ulcers?

Back 79

In advanced cases, cancerous craters can be identified by their heaped-up, beaded margins and shaggy necrotic bases, as well as by the overt neoplastic tissue extending into the surrounding mucosa and wall.

Uncommonly, a broad region of the gastric wall or the entire stomach is extensively infiltrated by malignancy, creating a rigid, thickened "leather bottle", termed linitis plastica.

Front 80

80. What is the morphology of the intestinal type (Laurén classification)?

Back 80

Gland forming columnar epithelium resembling colonic adenocarcinoma; usually mucin producing; usually polypoid expansile growth pattern.

Almost always associated with mucosal intestinal metaplasia.

Front 81

81. What is the morphology of the diffuse variant type (Laurén classification)?

Back 81

Poorly differentiated. This type is composed of gastric-type mucous cells, which generally do not form glands, but rather permeate the mucosa and wall as scattered individual cells or small clusters in an "infiltrative" growth pattern.

These cells appear to arise from the middle layer of the mucosa, and the presence of intestinal metaplasia is not a prerequisite.

Mucin formation expands the malignant cells and pushes the nucleus to the periphery, creating a "signet-ring" conformation. If the signet ring cells are more than 50% of the tumor, it is classified as a signet-ring carcinoma.

Front 82

82. Where do gastric carcinomas spread?

Back 82

All gastric carcinomas eventually penetrate the wall to involve the serosa and spread to regional and more distant lymph nodes.

For obscure reasons, gastric carcinomas freq metastasize to the supraclavicular sentinel (Virchow) node as the first clinical manifestation of an occult neoplasm.

Local invasion of gastric carcinoma into the duodenum, pancreas, and retroperitoneum is also characteristic.

Front 83

83. What is a Sister Mary Joseph nodule?

Back 83

The tumor can also metastasize to the periumbilical region to form a subcutaneous nodule.

This is a marker of metastatic carcinoma.

Front 84

84. What is a Krukenberg tumor?

Back 84

A notable site of visceral metastasis is to one or both ovaries.

Although uncommon, metastatic adenocarcinoma to the ovaries (from stomach, breast, pancreas and even gallbladder) is so distinctive as to be called Krukenberg tumor.

Front 85

85. What are the clinical features of gastric carcinomas?

Back 85

Gastric carcinoma is an insidious disease, initially asymptomatic, although patients exhibit weight loss, abdominal pain, anorexia, vomiting, altered bowel habits, dysphagia, anemia, and hemorrhage.

Prognosis after resection depends on depth of invasion and extend of nodal and distant metastases at time of Dx.

Front 86

86. What is a gastric lymphoma?

Back 86

AKA MALT lymphoma (mucosa associated lymphoid tissue) represents 5% of gastric malignancies.

They are associated w/H. pylori infection; antibiotic Tx can induce tumor regression.

Antibiotic-resistant tumors often harbor a t(11:18) translocation and Trisomy 3.

Front 87

87. Why is the t(11:18) translocation significant in antibiotic resistance?

Back 87

This translocation brings together the API2 (apoptosis inhibitor 2) gene on chromosome 11 w/ the MLT (mutated in MALT lymphoma) gene on chromosome 18.

The protein encoded by the fused genes is though to inhibit apoptosis.

Front 88

88. What is the morphology of gastric lymphomas?

Back 88

Commonly occurs in the mucosa or superficial submucosa.

In the MALT lymphoma, a monomorphic lymphocytic infiltrate of the lamina propria surrounds gastric glands massively infiltrated with atypical lymphocytes and undergoing destruction (the "lymphoid epitheliod" lesion)

These gut type lymphomas are usually CD5, CD10,a nd CD23 negative.

Rarely, Burkitt lymphoma, AIDS-associated lymphoma, and Hodgkin lymphoma may occur in the stomach.

Front 89

89. What are gastrointesitnal stromal tumors?

Back 89

It is though that GISTs originate from the interstitial cells of Cajal, which control gastrointestinal peristalsis.

These tumors have a special phenomenon in that 95% of them stain with antibodies against c-KIT, and approx 70% stain for CD34.

Front 90

90. What is the morphology of GIST?

Back 90

GISTs can be solitary or multiple. The tumor can protrude into the lumen with an overlying attenuated mucosa or extrude on the serosal side of the gastric wall.

The cut surface of the tumor is tan and usually lacks the whiling smooth muscle pattern of leiomyomas or leiomyosarcomas.

It varies from slightly firm to soft, and hemorrhagic changes are often seen. Necrosis or cystic changes can be seen in a large tumor.

Microscopically, the tumor can exhibit spindle cells, plump "epitheliod" cells, or a mixture of both.

Front 91

91. What is the pathogenesis of GIST?

Back 91

It is known that 85% of GISTs have c-KIT mutations, and 35% of GISTs w/normal c-KIT contain PDGFRA mutations.

Both c-KIT and PDGFRA have cytoplasmic tyrosine kinases that activate similar intracellular pathways. The mutations lead to constitutive activation of the tyrosine kinase signaling pathway, promoting cell proliferation and inhibiting apoptosis.

c-KIT mutations and PDGFRA mutations appear to be mutually exclusive.

Front 92

92. What are gastric neuroendocrine cell (carcinoid) tumors?

Back 92

Most gastric carcinoid tumors originate from the ECL cells in the oxytinc musosa. It can arise in the setting of chronic atrophic gastritis or MEN type I and Zollinger-Ellison syndrome.

The underlying pathogenesis is related to the hypergastrinemic state, resulting in ECL cell hyperplasia, a presumed pretumorous condition.

Front 93

93. What are lipomas?

Back 93

Lipomas are a benign neoplasm of adipose tissue, usually present in the submucosa.

Front 94

94. Metastatic involvement of the stomach

Back 94

Rare; the most common sources of gastric metastases are systemic lymphomas.

Metastases of malignant melanoma and carcinomas tend to be multiple and may develop central ulceration. Breast and lung CA may mimic diffuse carcinoma by diffusely infiltrating the gastric wall to generate linitis plastica.

Front 95

95. What are the four rare anomalies of gut formation?

Back 95

1. Duplication of the small intestine or colon, usually in the form of saccular to long, cystic structures.
2. Malrotation in the entire bowel, resulting form improper embryologic rotation of the gut.
3. Omphalocele, in which the abdominal musculature fails to form, leading to birth of an infant w/herniation of abdominal contents into a ventral membranous sac.
4. Gastroschisis, in which a portion of the abdominal wall fails to form altogether, causing extrusion of the intestines.

Front 96

96. What is Meckel diverticulum?

Back 96

Failure of involution of the vitelline duct, which connects the lumen of the developing gut to the yolk sac, produces a Meckel diverticulum.

This solitary diverticulum lies on teh antimesenteric side of the bowel, usually w/in 2 ft of the ileocecal valve.

It is a true diverticulum in that it contains all three layers of the normal bowel wall; mucosa, submucosa, and muscularis propria.

These diverticula are present in about 2% of the population.

Front 97

97. What is the morphology of Meckel diverticulum?

Back 97

Meckel diverticula may take the form of only a small pouch, or of a blind segment having a lumen greater in diameter than that of the ileum and a length of up to 6 cm.

Although the mucosal lining may be that of normal small intestine, heterotopic rests of gastric mucosa or pancreatic tissue are found in about 1/2 of these anomalies.

When peptic ulceration occurs in the small intestinal mucosa, intestinal bleeding or symptoms resembling those of an acute appendicitis may result.

Front 98

98. What is congenital aganglionic megacolon - aka Hirschsprung disease?

Back 98

Hirschsprung disease is a congenital disorder characterized by aganglionosis of a portion of the intestinal tract. The enteric neuronal plexus develops from neural crest cells, which migrate into the bowel wall during development, mostly in a cephalad to caudad direction.

This disease results when the migration of neural crest cells arrests at some point before reaching the anus or when the ganglion cells undergo inappropriate premature death.

Front 99

99. What is the cause of Hirschsprung?

Back 99

At least eight susceptibility genes have been identified. Mutations in these genes are associated w/varying degrees of intestinal aganglionosis and other congenital anomalies.

About 50% of familial cases and approx 15% of sporadic cases are a consequences of mutations in the RET gene that inactivate the kinase activity of this receptor. A much smaller proportion of cases (3-5%) may be caused by mutations in the endothelin/endothelin-receptor system.

*RET and its ligands promote survival and growth of neurites, and provide direction to migrating neural crest cells.

The endothelin system participates in the regulation of morphogenesis during embryonic development.

Front 100

100. What is the morphology of Hirschsprung disease?

1/2

Back 100

Hirschsprung disease is characterized by the absence of ganglion cells and ganglia in the muscle wall and submucosa of the affected segment. The rectum is always affected, w/involvement of more proximal colon to variable extent.

Most cases involve the rectum and sigmoid only (short-segment disease), with long segments in a fifth of cases, and rarely the entire colon (long-segment disease).

Absence of mural ganglion cells is sometimes accompanied by thickening and hypertrophy of nonmyelinated nerve fibers, representing ramifications of the lumbosacral preganglionic fibers.

Front 101

101. What is the morphology of Hirschsprung disease?

2/2

Back 101

Proximal to the aganglionic segment, the colon undergoes progressive dilation and hypertrophy, beginning with the descending colon. With time, the proximal innervated colon may become massively distended, sometimes achieving a diameter of 15-20 cm (megacolon).

When distention outruns the hypertrophy, the colonic wall becomes markedly thinned and may rupture usually near the cecum.

Mucosal inflammation or shallow, so called stercoral ulcers may appear.

Front 102

102. What are the clinical features of Hirschsprung disease?

Back 102

Occurs in 1:5000 to 1:8000 live births; M:F ratio is 4:1.

There is an association with Down syndrome and neurologic abnormalities. Hirschsprung disease presents w/neonatal failure to pass meconium or abdominal distention; patients risk perforation, sepsis, or enterocolitis with fluid and electrolyte derangement.

Front 103

103. What is acquired megacolon, and what four things can cause it?

Back 103

Acquired megacolon is a condition that may occur at any age and may result from:
1. Chagas disease, in which the trypanosomes directly invade the bowel wall to destroy the enteric plexuses
2. Organic obstruction of the bowel, by a neoplasm or inflammatory stricture
3. Toxic megacolon complicating UC or CD
4. A functional psychosomatic disorder

Front 104

104. What is diarrhea?

What is dysentery?

Back 104

Diarrhea is roughly defined as greater than 250 gm daily stool production, containing 70-95% water. Patients perceive it as increased stool volume, fluidity, or frequency.

Low volume, painful diarrhea is called dysentery.

Front 105

105. What are the different types of diarrhea?

Back 105

Secretory: net intestinal fluid secretion leads to the output of more than 500 mL of fluid stool per day, which is isotonic with plasma and persists during fasting

Osmotic: excessive osmotic forces exerted by luminal solutes leads to output of more than 500 mL of stool per day, which abates upon fasting

Exudative diseases: mucosal destruction leads to output of purulent, bloody stools that persist on fasting; stools are freq but may be small or large volume

Deranged motility; malabsorption

Front 106

106. What is the prevalence of infectious enterocolitis?

Back 106

This is a serious problem; half of all deaths before age 5 worldwide are due to infectious enterocolitis; it causes more than 12,000 deaths per day in children in developing countries.

In industrialized nations, individuals experience on average 1 or 2 episodes of vomiting or diarrhea per year.

Parasitic and protozoal disease affects more than 50% of the world's population on a chronic or recurrent basis.

Front 107

107. What is viral gastroenterocolitis?

Back 107

Incubation periods range from hours to days; acute illness lasts from 1-7 or more days. Besides diarrhea, anorexia, headache, and fever can develop.

Front 108

108. What are the four major causes of viral gastroenterocolitis?

Back 108

1. Rotavirus (group A)
2. Caliciviruses (Norwalk)
3. Enteric adenoviruses
4. Astroviruses

Front 109

109. What is the Rotavirus?

Back 109

Rotavirus (group A) is a 70-nm dsRNA virus. Person to person transmission via food and water; mainly affects infants 6-24 mos old.

Virus selectively infects and destroys mature small intesinal enterocytes; it accounts for 25-65% of severe childhood diarrhea (worldwide, 140 million cases and 1 million deaths annually)

Minimal infective inoculum is 10 particles, and infected hosts she 10^12 particles /mL of stool. Consequently, outbreaks are characteristic. Also, antirotavirus antibodies are present in mother's milk, so rotavirus infection is most freq at time of weaning.

Front 110

110. What are adenoviruses?

Back 110

Among the numerous types of adenoviruses, the subtypes (enteric serotypes) Ad40, 41, and 31 appear to be responsible for enteric infections and are a common cause of diarrhea among infants.

They can be distinguished from adenoviruses that cause respiratory disease by their failure to grow easily in culture.

Adenoviruses cause a moderate gastroenteritis w/diarrhea and vomiting, lasting for a week to 10 days after an incubation period of 1 week.

In the small intestine, adenoviral infection causes atrophy of the villi and compensatory hyperplasia of the crypts similar to rotavirus, resulting in malabsorption and fluid loss. The virus can also cause colitis.

Front 111

111. What are Caliciviruses?

Back 111

These include two major groups: Sapporo-like viruses, and the Norwalk-like viruses.

Sapporo-like infection is rare, while Norwalk virus is responsible for the majority of cases of nonbacterial food-borne epidemic gastroenteritis in all age groups.

Norwalk viruses are small icosahedral viruses containing single stranded RNA genome. They cause epidemic gastroenteritis w/diarrhea, nausea, and vomiting among children.

The clinical syndrome has an incubation period of 1-2 days, which is followed by 12-60 hours of nausea, vomiting, watery diarrhea, and abdominal pain.

Front 112

112. What are astroviruses?

Back 112

Astrovirus is named after its starlike appearance. It primarily affects children, and has a worldwide distro.

Those infected develop anorexia, headache, and fever. Other viruses such as the enterotrophic coronaviruses and toroviruses are occasionally implicated in human diarrheal disease.

Front 113

113. What is the morphology of viral gastroenterocolitis?

Back 113

Although the enteric viruses are genetically or morphologically different from each other, the lesions they cause in the intestinal tract are similar.

The small intestinal mucosa usually exhibits modestly shortened villi and infiltration of the lamina propria by lymphocytes. Vacuolization and loos of the microvillus brush border in surface epithelial cells may be evident, and the crypts become hypertrophied. Viral particles may be visualized by electron microscopy within surface epithelial cells.

In infants, rotavirus can produce a flat mucosa resembling celiac sprue.

Front 114

114. What are the mechanisms of injury with bacterial enterocolitis?

Back 114

1. Ingestion of preformed toxin in contaminated food (food poisoning), for example, Staph aureus, Vibrio species, Clostridium perfringens. Botulinum toxin is neurotoxic, not diarrheogenic.

2. Infection by toxigenic organisms (Vibrio cholerae, toxigenic E. coli), which proliferate in the gut lumen and elaborate toxins.

3. Infection by enteroinvasive organisms (Shigella, Salmonella, Yersinia, Campylobacter, enteroinvasive E. coli) that proliferate, invade and destroy mucosal epithelial cells.

Front 115

115. What are the three main properties of bacteria that contribute to the pathogenesis of enterocolitis?

Back 115

1. The ability to adhere to the mucosal epithelial cells and replicate
2. The ability to elaborate enterotoxins
3. The capacity to invade

Front 116

116. What is bacterial adhesion and replication?

Back 116

In order to produce disease, ingested organisms must adhere to the mucosa; otherwise they will be swept away by the fluid stream.

Adherence of enterotoxigenic organisms such as E. coli and Vibrio cholerae is mediated by plasmid-encoded adhesins. These proteins are expressed on the surface of the organism, sometimes int he form of fimbriae or pili, which are rigid or wiry surface projections.

Adherence of enteropathogenic and enterohemorrhagic organisms, including E. coli and Shigella, is also dependent on plasmid-encoded proteins.

Front 117

117. What can adherence result in?

Back 117

Adherence causes effacement of the apical enterocyte membrane, w/destruction of the microvillus brush border and changes in the underlying cell cytoplasm.

Front 118

118. What are bacterial enterotoxins?

Back 118

Bacterial enterotoxins are polypeptides that cause diarrhea.

Two mechanisms are involved (E. coli can produce both toxin forms):
1. Secretagogues (e.g. cholera toxin from Vibrio cholerae) stimulate fluid secretion by activating endogenous secretion pathways
2. Cytotoxins (e.g. Shiga toxin) cause direct tissue damage via epithelial cell necrosis.

Front 119

119. What is the major cause of traveler's diarrhea?

Back 119

Strains of E. coli (enterotoxigenic E. coli) that produce heat-labile (LT) and heat-stable (ST) secretagogue toxins are the major cause of traveler's diarrhea.

The LT toxin is similar to cholera toxins, and the ST toxin induces cGMP, resulting in increased fluid excretion.

Leukocytes are absent from the stool of patients w/travelers diarrhea.

Front 120

120. What are cytotoxins?

Back 120

A second group of enterotoxins are cytotoxins, exemplified by Shiga toxin produced by Shigella dysenteriae and Shiga-like toxins produced by enterohemorrhagic E. coli (e.g. E. coli O157:H7)

These toxins cause direct tissue damage through epithelial cell necrosis.

Front 121

121. What are Staphylococcal enterotoxins?

Back 121

Staphylococcal enterotoxins, which are major causes of food poisoning, represent yet another group of enterotoxins; they are presents that bind to the antigen receptors of large numbers of T cells and activate the lymphocytes to secrete cytokines.

The cytokines then stimulate intestinal motility and fluid secretion.

Front 122

122. Define bacterial invasion

Back 122

Both enteroinvasive E. coli and Shigella possess a large virulence plasmid that confers the capacity for epithelial cell invasion, apparently by microbe-stimulated endocytosis. This is followed by intracellular proliferation, cell lysis and cell-to-cell spread.

Salmonella quickly pass through intestinal epithelial cells via transcytosis w/minimal epithelial damage; entry into the lamina propria leads to a 5-10% incidence of bacteremia, which can sometimes cause typhoid fever, meningitis, endocarditis, and osteomyelitis.

Front 123

123. How does Yersinia enterocolitica invade?

Back 123

Yersinia enterocolitica penetrates the ileal mucosa and multiplies within Peyer patches and regional lymph nodes.

Bactermeia is rare and usually occurs in the setting of iron-overload disease, since iron is a growth factor for Yersinia.

Front 124

124. How do bacterial cytotoxins and invasion give rise to bacillary dysentery?

Back 124

This causes abdominal cramping and tenesmus w/loose stools containing blood, pus, and mucus.

Bacillary dysentery, which results in as many as 500,000 deaths/year is caused by Shigella dysenteriae, Shigella felxneri, Shigella boydii, and Shigella sonnei as well as certain O type enterotoxic E. coli.

Front 125

125. What is Shigella bacillary dysentery?

Back 125

Shigella species are gram negative facultative anaerobes that infect only humans.

S. flexneri is the major cause of endemic bacillary dysentery in locations of poor hygiene, including large regions of the developing owrld and institutions in the developed world.

Epidemic shigellosis can occur when individuals consume uncooked food at picnics or other events.

Front 126

126. What is the pathogenesis of Shigella bacillary dysentery?

Back 126

Transmission is fecal-oral and is remarkable for a small amt of ingested organisms (10 ingested cause illness in 10%)

Shigella bacteria invade the intestinal mucosal cells but do not usually go beyond the lamina propria. Dysentery is caused when the bacteria escape the epithelial cell phagolysosome, multiply within the cytoplasms, and destroy host cells.

Shiga toxin causes hemorrhagic colitis and HUS syndrome by damaging endothelial cells in the microvasculature of the colon and glomeruli.

Front 127

127. What is Reiter syndrome?

Back 127

In addition, chronic arthritis secondary to S. flexneri infection, called Reiter syndrome, may be caused by a bacterial antigen; the occurrence of this syndrome is strongly linked to HLA-B27 genotype.

Front 128

128. What is the morphology of Shigella bacillary dysentery?

Back 128

Shigella primarily affects the distal colon, first w/hypemeia and edema and enlargement of mucosal lymphoid nodules, creating small projecting nodules.

Within 24 hours, the acute mucosal inflammation and erosion generate a patchy and then confluent purulent exudate.

The mucosa then becomes soft and friable, and irregular ulcerations appear; severe infection generates large denuded tracts of mucosa. The recovery phase is marked by formation of mucosal granulation tissue and eventual regeneration of the mucosal epithelium.

Front 129

129. What is samonellosis and typhoid fever?

Back 129

Salmonellae are flagellated, gram negative bacteria that cause a self limited food-borne and water-borne gastroenteritis or a life threatening systemic illness, typhoid fever, marked by fever and systemic symptoms (S. typhi).

The major sources of Salmonella in the US are feces contaminated beef and chicken that are insufficiently washed and cooked.

In contrast, humans are the only host of S. typhi, which is shed in the feces, urine, vomitus, and oral secretion by acutely ill persons and in the feces by chronic carriers w/o overt disease.

Front 130

130. What is typhoid fever?

Back 130

Typhoid fever from S. typhi is a disease largely of developing countries, where sanitary conditions are insufficient.

Typhoid fever is a protracted disease that is associated w/bacteremia, fever, and chills during the first week; widespread mononuclear phagocyte involvement w/rash, abdominal pain, and prostration in the second week; and ulceration of Peyer patches with intestinal bleeding and shock during the third week.

Front 131

131. What is the pathogenesis of Salmonellosis?

Back 131

Salmonella invades intestinal epithelial cells as well as tissue macrophages.

Invasion is controlled by invasion genes that are induced by the low oxygen tension found in the gut. These genes encode proteins involved in adhesion and in recruitment of host cytoskeletal proteins that internalize the bacterium.

Similarly, intramacrophage growth is important in pathogenicity, and this seems to be mediated by bacterial genes that are induced by the acid pH within the macrophage phagolysosome.

Front 132

132. What is the morphology of Salmonellosis ?

Back 132

Salmonella primarily affects the ileum and colon, generating blunted villi, vascular congestion, and mononuclear inflammation.

Peyer patch involvement produces swelling, congestion, and eventual ulceration with linear ulcers.

Front 133

133. What is the morphology of Typhoid fever?

1/2

Back 133

With S. typhi, bacteremia and systemic dissemination cause proliferation of phagocytes w/enlargement of reticuloendothelial and lymphoid tissues throughout the body.

Peyer patches become sharply delineated, plateau like elevation of up to 8 cm in diameter, w/enlargement of draining mesenteric lymph nodes.

Shedding of the mucosa and swollen lymphoid tissue creates oval ulcers with their long axes along the axis of the ileum.

Front 134

134. What is the morphology of Typhoid fever?

2/2

Back 134

Microscopic exam reveals macrophages containing bacteria, RBCs, and nuclear debris. Intermingled w/the phagocytes are lymphocytes and plasma cells, whereas neutrophils are present near the ulcerated surface.

The spleen is enlarged, soft and bulging with uniformly pale red pulp, obliterated follicular markings, and prominent sinus histiocytosis and reticuloendothelial proliferation.

*The liver shows small, randomly scatter foci of parenchymal necrosis in which the hepatocytes are replaced by a phagocytic mononuclear aggregate, called a typhoid nodule. These distinctive nodules also occur in the bone marrow and lymph nodes.

Front 135

135. What is Campylobacter enterocolitis?

Back 135

This comma shaped, flagellated, gram negative organism is an important cause of enterocolitis.

Most infections are sporadic and are assoc with ingestion of improperly cooked chicken, which may be contaminated with Campylobacter and/or Salmonella.

Sporadic infections may also be assoc with contact with infected dogs. Outbreaks are usually assoc with unpasteurized milk or contaminated water.

Front 136

136. What is the pathogenesis of Campylobacter enterocolitis?

Back 136

Invasiveness is strain dependent.

Flagella, which give the organism its comma shape and motility, are necessary for the bacterium to penetrate mucus covering epithelial surfaces.

Front 137

137. What are the three clinical outcomes of Campylobacter infection?

Back 137

1. Diarrhea, which is independent of bacterial invasion
2. Dysentery w/blood and mucus in the stool
3. Enteric fever when bacteria proliferate within the lamina propria and mesenteric lymph nodes

Front 138

138. What are the postinfectious complications of Campylobacter infection?

Back 138

1. Reactive arthritis in HLA-B27 carriers (as with Shigella infection)
2. Guillain-Barre syndrome, a demyelinating disease of peripheral nerves due to autoantibodies against gangliosides.

Front 139

139. What is the morphology of Campylobacter infection?

Back 139

C. jejuni and other species may involve the entire intestine from the jejunum to the anus.

The small intestine exhibits a decrease in the villus to crypt ratio. In invasive colonic infection, the colonic mucosa appears friable and superficially eroded.

Histology reveals multiple superficial ulcers, mucosal inflammation and a purulent exudate. The formation of colonic crypt abscesses and mucosal ulceration may be confused with those of UC.

Front 140

140. What is V. cholerae infection?

Back 140

Vibrio choleae are comma shaped, gram negative bacteria that have been the cause of seven epidemics.

The vibrios never invade the epithelium but instead remain within the lumen and secrete and enterotoxin, which is encoded by a virulence phage. Flagellar proteins involved in motility and attachment are necessary for efficient bacterial colonization.

The Vibrio hemagglutinin, which is a metalloprotease, is important for the detachment of Vibrio from epithelial cells.

Front 141

141. What is the pathogenesis of V. cholerae infection?

Back 141

The secretory diarrhea characteristic of the disease is caused by release of cholera toxin. Cholera toxin is composed of five binding peptides B and a catalytic peptide A.

The B peptides serve as landing pads that bind to carbs on gangliosides on the surface of epithelial cells of the small intestine, enabling endosomal entry of toxin subunit A into the cell.

Front 142

142. Binding of the subunit A into the cell does what?

Back 142

1. Peptide A1 is generated
2. A1 interacts w/cytosolic proteins caused ADP ribosylation factors (ARF)
3. The ARF-A1 complex catalyzes ADP ribosylation of a G-protein
4. Binding of NAD and GTP generates and activated G protein which binds to and stimulates adenylate cyclase; this causes persistent activation
5. The activated adenylate cyclase generates high levels of intracellular cAMP from ATP
6. cAMP stimulates secretion of chloride and bicarb, with associated sodium and water secretion. Chloride and sodium resorption are also inhibited.

Front 143

143. What are the clinical features of cholera?

What are the morphological findings?

Back 143

The resorptive function of the colon is overwhelmed, and liters of dilute "rice water" diarrhea containing flecks of mucus causes dehydration and electrolyte imbalances.

It principally affects the small intestine, esp the more proximal segment. The mucosa remains intact, with mucus depleted crypts.

Front 144

144. What is pseudomembranous colitis?

Back 144

This entity is characterized by formation of an adherent layer of inflammatory cells and debris overlying sites of mucosal injury, a so-called pseudomembrane.

It is usually caused by Clostridium difficile, a normal gut commensal.

The disease occurs most often in patients following a course of broad spectrum antibiotics. It occurs primarily in adults as an acute or chronic diarrheal illness.

Front 145

145. What is the morphology of pseudomembranous colitis?

Back 145

C. difficile induced pseudomembranous colitis derives its names from the plaque like adhesion of fibrinopurulent-necrotic debris and mucus to damaged colonic mucosa. Psueodomembrane formation is not restricted to C. difficile; it may also occur following any severe mucosal injury, as in ischemic colitis, volvulus, and with necrotizing infections.

The surface epithelium is denuded, and the superficial lamina propria contains a dense infiltrate of neutrophils and occasionall capillary fibrin thrombi.

Superficially damaged crypts are distended by mucopurulent exudate, which erupts out of the crypt to form a mushrooming cloud that adheres to the damaged surface - the coalescence of this "cloud" forms the psuedomembrane.

Front 146

146. What is enteropathogenic E. coli?

Back 146

At least four different types of pathogenic E. coli are known to cause significant diseases ; the enterotoxigenic (ETEC), enterhemorrhagic (EHEC), enteroinvasive (EIEC), and enteradherent (mainly, enteropathogenic (EPEC).

In the US, the most important one is the EHEC serotype E. coli O157:H7. EHEC are intestinal commensals in many animals. Humans are usually infect by contaminated meat. These bacteria produce Shiga-like toxins, which damage enterocytes and vascular endothelial cells. In addition to abdominal pain and diarrhea, some patients may develop life threatening HUS syndrome.

Front 147

147. What are the nematodes that cause parasitic enterocolitis?

Back 147

1. Asaris
2. Strongyloides
3. Hookworms
4. Pinworms (enterbius vermicularis)
5. Whipworms (Trichuris trichiura)

Front 148

148. Ascaris lumbricoides

Back 148

Most common nematode. Fecal oral transmission occurs with intestine-liver-lung-intestine life cycle.

They can cause physical obstruction of intestine or biliary tract, hepatic abscesses, or Ascaris pneumonitis.

Front 149

149. Strongyloides

Back 149

Life cycle begins with penetration of skin or intestinal mucosa progressing sequentially to lung and intestine.

They typically incite strong tissue eosinophil reactions. Autoinfections (intestinal luminal larvae penetrate the mucosa and directly invade into the body) can be fatal in immunocompromised individuals.

Front 150

150. Hookworm (Necator duodenale and Ancylostoma duodenale)

Back 150

Life cycle begins with larvae pentration through skin-lung-duodenum.

Worms attach to mucosa and extract blood, causing mucosal damage and iron deficiency anemia.

Front 151

151. Pinworms (enterbius vermicularis)

Back 151

Transmission is fecal-oral; entire life cycle occurs in the intestinal lumen.

No direct tissue invasion occurs; adult worms migrate to anal orifice where eggs are deposited, causing irritation and pruritus.

Front 152

152. Whipworms (Trichuris trichiura)

Back 152

Infection primarily affects children.

No direct tissue invasion occurs; heavy infections cause bloody diarrhea and rectal prolapse.

Front 153

153. What are the three species of cestodes?

Back 153

1. Diphyllobothrium latum (fish tapeworm)
2. Hymenolepsis nana (dwarf tapeworm)
3. Taenia solium (pork tapeworm)

Front 154

154. How do cestode infections occur?

Back 154

Infection occurs by ingestion of raw or undercooked meat that contains encysted larvae.

Release of the larvae enables attachment to the intestinal mucosa through its head, or scolex.

Parasites remain within the lumen without tissue invasion; proglottids contain eggs.

Front 155

155. What is Entamoeba histolytica (ameba)?

Back 155

Entamoeba histolytica (ameba) is a dysentry causing protozoan parasite spread by fecal-oral transmission.

This protozoan infects approx 500 million persons in developing countries such as India, Mexico, and Colombia, resulting in approx 40 million cases of dysentery and liver abscess.

Front 156

156. What is the pathogenesis of E. histolytica cysts?

1/2

Back 156

E. histolytica cysts, which have a chitin wall and 4 nuclei, are the infectious form b/c they are resistant to gastric acid. Ingested quadrinucleate cysts colonize the surface of colonic mucin epithelial cells. Cysts release trophozoites, the ameboid forms, which reproduce under anaerobic conditions w/o harming the host.

B/c the parasites lack mitochondria or Krebs cycle enzymes, amebae are obligate fermenters of glucose to ethanol.

Metronidazole is used to fight infection b/c it targets ferridoxin-dependent pyruvate oxidoreductase, an enzyme critical in fermentation.

Front 157

157. What is the pathogenesis of E. histolytica cysts?

2/2

Back 157

Amebae cause dysentery when they attach to the colonic epithelium, as they cause epithelial cell apoptosis, invade the crypts of colonic glands,and burrow into the lamina propria.

The organisms then burrow laterally to create with inflammation and tissue necrosis, a "flask shaped" ulcer with a narrow neck and broad base.

Front 158

158. What three amebic proteins are involved in tissue invasion?

Back 158

1. Cysteine proteinases, which are able to break down proteins of the extracellular nature
2. A lectin on the parasite surface that binds to carbs on the surface of colonic epithelial cells and RBCs
3. A channel forming protein called the amebapore, which makes holes in the plasma membrane of host cells and lyses them.

The presence in stool of trophozoites containing ingested RBCs is indicative of tissue invasion by virulent organisms.

Front 159

159. What is the morphology of amebiasis?

Back 159

Human infection is caused by ingesting cysts; Amebiasis most frequently involves the cecum and ascending colon.

Amebae can mimic the appearance of macrophages, however, the parasites have a smaller nucleus, which contains a large karyosome. Amoebae cause epithelial damage with gland invasion and formation of flask-shaped ulcers (narrow neck and broad base).

The maturing ulcers contain few host inflammator cells and exhibit extensive liquefactive necrosis.

Amebae can also cause liver abscess, but rarely systemic infection.

Front 160

160. What is the morphology of amebic liver abscesses?

Back 160

Amebic liver abscesses have a scant inflammatory reaction at their margins and a shaggy fibrin lining. B/c of hemorrhage into the cavities, the abscesses are sometimes filled with a chocolate colored, odorless, pasty material.

Secondary bacterial infection may make these abscesses purulent.

Front 161

161. What are the clinical features of amebiasis?

Back 161

Clinically, the patient may present with abdominal pain, bloody diarrhea, or weight loss. Occasionally, acute necrotizing colitis and megacolon can occur, which carry significant mortality.

Rarely, amebic abscesses reach the lung and the heart by direct extension from the liver or spread from the liver through the blood into the kidneys and brain. Such abscesses remain long after the acute intestinal illness has passed.

Front 162

162. What organism causes Giardiasis?

Back 162

Giardia lamblia is the most common pathogenic parasitic infection in humans. It is an intestinal protozoan spread by fecally contaminated water or food. Infection may be subclinical or may cause acute or chronic diarrhea, steatorrhea, or constipation.

Front 163

163. What is the pathogenesis of Giardiasis?

Back 163

Giardia ferments glucose, lacks mitochondria, and exists in two forms: (1) a dormant but infectious cyst spread by the fecal-oral route from person to person; and (2) trophozoites that multiply in the intestinal lumen

Front 164

164. What causes the transition from trophozoites to cysts?

Back 164

The transition is induced by decreases in availability of cholesterol as Giardia moves from duodenum to jejunum.

Giardia trophozoites have two nuclei rather than one, are flagellated, reside in the duodenum, adhere to but do not invade the intestinal epithelial cells, and so cause diarrhea rather than dysentery.

Front 165

165. Why is Giardia toxigenic?

Back 165

With as few as 10 cysts, tight contact between the parasite and the epithelial cell in the duodenum is made by a sucker-like disc.

Although Giardia does not secrete toxin, it contains a cysteine rich surface protein that resembles diarrhea-causing toxins secreted by certain snakes.

Front 166

166. What mediates immunity in Giardia?

Back 166

Immunity mediated by antibodies, including secretory IgA, is important in resistance to Giardia, b/c agammaglobulinemic individuals are severely affected by the parasite.

Front 167

167. What is the morphology of Giardiasis?

Back 167

In stool smears, G. lamblia trophozoites are pear shaped and binucleate.

Duodenal biopsy specimens are often teeming w/sickle-shaped trophozoites, which are tightly bound by the concave attachment disc.

Small intestinal morphology may be normal, however; many patients exhibit marked blunting of the small intestinal villi.

Sort of looks like the atrophy stage of celiac disease.

Front 168

168. What are the clinical features of Giardiasis?

Back 168

Infected patients exhibit a malabsorptive diarrhea, owing to mucosal epithelial cell injury.

Functional lactase deficiency also occurs in 20-40% of chronically infected patients by mechanisms that are not understood.

While giardiasis is responsive to oral antimicrobial therapy, recurrence is common following cessation of treatment.

Front 169

169. What is necrotizing enterocolitis?

Back 169

NEC is an acute, necrotizing inflammation of the small and large intestines with the severe consequence of transmural necrosis of intestinal segments.

It is the most common acquired GI emergency of neonates, particularly those who are premature or of low birth weight.

Front 170

170. What is collagenous colitis?

Back 170

Collagenous colitis is a disorder of the colon characterized by chronic watery diarrhea and patches of "bandlike" collagen deposits directly under the surface epithelium.

This disease shows a strong association with autoimmune diseases.

Front 171

171. What is lymphocytic colitis?

Back 171

lymphocytic colitis is characterized by chronic watery diarrhea and a prominent intraepithelial infiltrate of lymphocytes.

Front 172

172. What is AIDS enteropathy?

Back 172

Diarrheal illnesses occurs in AIDS patients. Some exhibit a malabsorptive syndrome w/small intestinal villus atrophy or a colitic syndrome resembling ulcerative colitis. in the absence of demonstrable pathogens.

Besides other known infectious organisms, HIV is though to directly affect mucosal epithelium.

Front 173

173. Transplantation issues

Back 173

Transplantation (bone marrow especially) can result in graft-vs.-host disease involving the gut mucosa; it can be fatal.

Characteristic histologic findings include a mild lymphocytic infiltrate and associated crypt epithelial cell apoptosis.

Front 174

174. What is drug induced intestinal injury?

Back 174

Drug induced intestinal injury most commonly occur when a pill adheres to the mucosa and releases all of its contents locally.

It manifests as focal ulceration or mucosal inflammation from NSAID use.

Front 175

175. What is radiation enterocolitis?

Back 175

Acute radiation enteritis manifests as anorexia, abdominal cramps, and malabsorptive diarrhea, attributable to acute mucosal injury.

Chronic radiation may exhibit more indolent symptoms than the acute form or may present as an inflammatory colitis.

Front 176

176. What is neutropenic colitis (typhlitis)

Back 176

Neutropenic colitis is a life-threatening acute inflammatory destruction of the cecal region occurring in neutropenic patients (i.e. after bone marrow transplant).

It is attributed to impaired mucosal immunity in conjunction with compromised blood flow.

Front 177

177. What is diversion colitis?

Back 177

Diversion colitis is an iatrogenic inflammatory colitis occurring after surgical diversion of the fecal stream (as with an enterostomy).

It is proposed that the lack of short-chain fatty acid delivery to the mucosa (i.e adequate nutrition) is responsible for this disorder.

Microscopically, there is a chronic lymphooplasmacytic inflammation, and a characteristic lymphoplasmacytic inflammation, and a characteristic lymphoid follicular hyperplasia.

Front 178

178. What is solitary rectal ulcer syndrome?

Back 178

Solitary rectal ulcer syndrome is attributed to dysregulation of the anorectal sphincter, causing acute angulation of the anterior rectal shelf and overlying mechanical abrasion.

Patients present with rectal bleeding and mucus discharge. Microscopically, there is distorted, cystically dilated glands surrounded by proliferating smooth muscle cells.

Front 179

179. What malabsorptive disorders are most commonly encountered in the US?

Back 179

Celiac disease, pancreatic insufficiency, and Crohn disease

Pancreatic insufficiency, primarily from chronic pancreatitis or CF, is a major cause of defective intraluminal digestion.

Front 180

180. What is celiac disease?

Back 180

Celiac disease (AKA sprue) is a chronic disease, in which there is a characteristic mucosal lesion of the small intestine and impaired nutrient absorption, which improves on withdrawal of wheat gliadins and related grain proteins from the diet.

It occurs largely in whites and occurs in the range of 1/100 to 1/200.

Front 181

181. What is the pathogenesis of celiac disease?

What is the hallmark of this disease?

Back 181

The fundamental disorder is a sensitivity to gluten, which is the alcohol soluble, water insoluble protein component (gliadin) of wheat and closely related gains (oat, barley, and rye).

The hallmark of this disease is a T-cell mediated chronic inflammatory reaction w/an autoimmune component, which most likely develops as a consequence of a loss of tolerance to gluten.

The small intestinal mucosa, when exposed to gluten, accumulates intraepithelial CD8+ T cells and large numbers of lamina propria CD4+ T cells, which are sensitized to gliadin.

Front 182

182. What genetic factors are associated w/celiac disease?

Back 182

Almost all individuals w/celiac share the MHC complex class II HLA-DQ2 or HLA-DQ8 haplotype.

It has been suggested that gliadin is deamidated by the enzyme transglutaminase and that deaminadated gliadin peptides bind to DQ2 and DQ8.

Recognition of these peptides by CD4+ T cells leads to secretion of interferon γ, which damages the intestinal wall.

Front 183

183. Why is celiac disease associated w/lymphoma?

Back 183

The epithelial cells secrete large amts of IL-15 that activates CD8+ T cells and increases the risk of lymphoma development.

Front 184

184. What is the morphology of celiac disease?

1/2

Back 184

By endoscopy, the small intestinal mucosa appears flat or scalloped, or may be visually normal. Biopsies demonstrate diffuse enteritis, with marked atrophy or total loss of villi.

The surface epithelium shows vacuolar degeneration, loss of the microvillus brush border, and an increased number of intraepithelial lymphocytes.

The crypts, on the other hand, exhibit increased mitotic activity and are elongated, hyperplastic and tortuous, so that the overall mucosal thickness remains the same.

Front 185

185. What is the morphology of celiac disease?

2/2

Back 185

The lamina propria has an overall increase in plasma cells, lymphocytes, macrophages, eosinophils, and mast cells. All these changes are usually more marked in the proximal small intestine than in the distal, since it is the duodenum and proximal jejunum that are exposed to the highest concentration of dietary gluten.

Although these changes are characteristic of celiac disease, they can be mimicked by other diseases, most notably tropical sprue.

Mucosal histology usually reverts to normal or near-normal following a period of gluten exclusion from the diet.

Front 186

186. What are the clinical features of celiac disease?

Back 186

The symptoms vary from patient to patient. Symptomatic diarrhea and failure to thrive may be evident during infancy, yet adults may seek attention much later in life.

The classic presentation includes diarrhea, flatulence, weight loss, and fatigue. However, extraintestinal manifestations of malabsorption may overshadow the intestinal symptoms.

A characteristic skin blistering lesion, dermatitis herpetiformis, can occur in patients w/celiac disease.

Neurologic disorders are occasionally seen.

Front 187

187. Dx of celiac disease?

Definitive Dx depends on what 3 things?

Back 187

Detection of circulating anti-gliadin or "anti-endomysial" antibodies strongly favors the Dx; antibodies against tissue transglutaminase also may be detected, as this is the autoantigen recognized by anti-endomysial antibody.

Definitive Dx rests on:
1. Clinical documentation of malabsorption
2. Demonstration of the intestinal lesion by small bowel biopsy
3. Unequivocal improvement in both symptoms and mucosal histology on gluten withdrawal from the diet

Front 188

188. What is the prognosis of those w/celiac disease?

Back 188

Most patients w/celiac disease who adhere to a gluten free diet remain well indefinitely and ultimately die of unrelated causes.

However, there is a long term risk of malignant disease, which includes non-Hodgkin lymphoma, small intestinal adenocarcinoma, and esophageal squamous cell carcinoma.

Front 189

189. What is tropical sprue?

Back 189

This condition is a celiac like disease that occurs almost exclusively in people living in or visiting the tropics.

No specific causal agent has been clearly associated w/tropical sprue, but bacterial overgrowth by enterotoxigenic organisms (E. coli and Hemophilus) has been implicated.

Malabsorption usually becomes apparent w/in days or a few weeks of an acute diarrheal enteric infection in visitors to endemic locales and may persist if untreated. The mainstay of treatment is broad spectrum antibiotics.

Front 190

190. What is the morphology of tropical sprue?

Back 190

Intestinal changes are extremely variable, ranging from near normal to severe diffuse enteritis. Unlike celiac sprue, injury is seen at all levels of the small intestine.

Patients freq have folate and or vitamin B12 deficiency, leading to markedly atypical enlargement of the nuclei of epithelial cells (megaloblastic change), reminiscent of the changes seen in pernicious anemia.

Front 191

191. What is whipple disease?

Back 191

Whipple disease is a rare disease caused by the bacterium Tropheryma whippelii. It is a systemic condition that may involve any organ of the body, but principally affects the intestine, CNS, and joints.

The causal organism T. whippelii is a gram positive actinomycete, named on the basis of molecular phylogenetic analysis. The bacteria proliferate preferentially within macrophages and invoke no significant host immune reaction.

Front 192

192. What is the morphology of whipple disease?

What is the hallmark?

Back 192

The hallmark is a small intestinal mucosa laden with distended macrophages in the lamina propria. The macrophages contain PAS positive, diastase-resistant granules (which are lysosomes stuffed w/partially digested microorganisms) and rod-shaped bacilli on electron microscopy.

In untreated cases, the bacilli can be seen as well in neutrophils, the extracellular space of the lamina propria, and even in epithelial cells. Expansion of the villi by the dense infiltrate of macrophages imparts a shaggy gross appearance the the intestinal mucosal surface; edema of the mucosa thickens the intestinal wall. Accompanying these changes is involvement of the mesenteric lymph nodes by the same process and lymphatic dilation, suggesting lymphatic obstruction. The lymphatic blockade is believed to be responsible for lipid desposition in the villi, thus the origianl impression of intestinal lipodystrophy.

Bacilli-laden macrophages also can be found in the synovial membranes of affected joints, the brain, cardiac valves, and elsewhere. At each of these sites, inflammation is essentially absent. Functional impairment can be considerable at each affected site.

Front 193

193. What are the clinical features of Whipple disease?

Back 193

Whipple disease is principally encountered in whites in the fourth to fifth decade of life, with a strong male predominance of 10:1. Many cases come from rural regions, suggesting an environmental influence.

It usually present as a form of malabsorption with diarrhea and weight loss, sometimes of years' duration.

Arthropathy is often the inital presentation. Atypical presentations, with polyarthritis, obscure psychiatric complaints, cardiac abnormalities, and other symptom complexes are common. Lymphadenopathy and hyperpigmentation are present in over half the cases.

Currently the Dx rests on demonstration of small intestinal PAS-positive macrophages that contain rod-shaped organisms.

Response to antibiotic therapy is usually prompt, although some patients have a protracted, refractory course.

Front 194

194. What is abetalipoproteinemia?

Back 194

Inability to synthesize apolipoprotein B is a rare inborn error of metabolism transmitted by autosomal recessive inheritance.

It is characterized by a defect in the synthesis and export of lipoproteins from intestinal mucosal cells. Free fatty acids and monoglycerides that are produced by hydrolysis of dietary fat enter the absorptive epithelial cells and are re-esterified in the normal fashion but cannot be assembled into chylomicrons.

As a consequence, triglycerides are stored within the cells, creating lipid vacuolation that is readily evident under the light microscope, particularly with special fat stains. Concomitantly, there is complete absence in plasma of all lipoproteins containing apolipoprotein B (chylomicrons, very-low-density lipoproteins, and low-density lipoproteins).

The failure to absorb certain essential fatty acids leads to lipid membrane defects, readily evident in the characteristic acanthocytic erythrocytes (burr cells). The disease becomes manifest in infancy and is dominated by failure to thrive, diarrhea, and steatorrhea.