Pbl Exam 6 Case 2

Front 1

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

Back 1

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 2

2. What is Meckel diverticulum?

Back 2

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 3

3. What is the morphology of Meckel diverticulum?

Back 3

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 4

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

Back 4

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 5

5. What is the cause of Hirschsprung?

Back 5

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 6

6. What is the morphology of Hirschsprung disease?

1/2

Back 6

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 7

7. What is the morphology of Hirschsprung disease?

2/2

Back 7

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 8

8. What are the clinical features of Hirschsprung disease?

Back 8

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 9

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

Back 9

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 10

10. What is diarrhea?

What is dysentery?

Back 10

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 11

11. What are the different types of diarrhea?

Back 11

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 12

12. What is the prevalence of infectious enterocolitis?

Back 12

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 13

13. What is viral gastroenterocolitis?

Back 13

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

Front 14

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

Back 14

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

Front 15

15. What is the Rotavirus?

Back 15

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 16

16. What are adenoviruses?

Back 16

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 17

17. What are Caliciviruses?

Back 17

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 18

18. What are astroviruses?

Back 18

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 19

19. What is the morphology of viral gastroenterocolitis?

Back 19

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 20

20. What are the three different mechanisms of injury with bacterial enterocolitis?

Back 20

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 21

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

Back 21

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

Front 22

22. What is bacterial adhesion and replication?

Back 22

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 23

23. What can adherence result in?

Back 23

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

Front 24

24. What are bacterial enterotoxins?

Back 24

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 25

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

Back 25

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 26

26. What are cytotoxins?

Back 26

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 27

27. What are Staphylococcal enterotoxins?

Back 27

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 28

28. Describe bacterial invasion for EIEC, Shigella, and Salmonella

Back 28

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 29

29. How does Yersinia enterocolitica invade?

Back 29

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 30

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

Back 30

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 31

31. What is Shigella bacillary dysentery?

Back 31

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 32

32. What is the pathogenesis of Shigella bacillary dysentery?

Back 32

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 33

33. What is Reiter syndrome?

What genotype is it linked with?

Back 33

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 34

34. What is the morphology of Shigella bacillary dysentery?

Back 34

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 35

35. What is samonellosis and typhoid fever?

Back 35

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 36

36. What is typhoid fever?

Back 36

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 37

37. What is the pathogenesis of Salmonellosis?

Back 37

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 38

38. What is the morphology of Salmonellosis ?

Back 38

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 39

39. What is the morphology of Typhoid fever?

1/2

Back 39

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 40

40. What is the morphology of Typhoid fever?

2/2

Back 40

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 41

41. What is Campylobacter enterocolitis?

Back 41

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 42

42. What is the pathogenesis of Campylobacter enterocolitis?

Back 42

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 43

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

Back 43

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 44

44. What are the two postinfectious complications of Campylobacter infection?

Back 44

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 45

45. What is the morphology of Campylobacter infection?

Back 45

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 46

46. What is V. cholerae infection?

Back 46

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 47

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

Back 47

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 48

48. Binding of the subunit A into the cell does what six things?

Back 48

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 49

49. What are the clinical features of cholera?

What are the morphological findings?

Back 49

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 50

50. What is pseudomembranous colitis?

Back 50

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 51

51. What is the morphology of pseudomembranous colitis?

Back 51

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 52

52. What is enteropathogenic E. coli?

Back 52

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 53

53. What are the nematodes that cause parasitic enterocolitis?

Back 53

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

Front 54

54. Ascaris lumbricoides

Back 54

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 55

55. Strongyloides

Back 55

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 56

56. Hookworm (Necator duodenale and Ancylostoma duodenale)

Back 56

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 57

57. Pinworms (enterbius vermicularis)

Back 57

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 58

58. Whipworms (Trichuris trichiura)

Back 58

Infection primarily affects children.

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

Front 59

59. What are the three species of cestodes?

Back 59

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

Front 60

60. How do cestode infections occur?

Back 60

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 61

61. What is Entamoeba histolytica (ameba)?

Back 61

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 62

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

1/2

Back 62

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 63

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

2/2

Back 63

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 64

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

Back 64

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 65

65. What is the morphology of amebiasis?

Back 65

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 66

66. What is the morphology of amebic liver abscesses?

Back 66

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 67

67. What are the clinical features of amebiasis?

Back 67

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 68

68. What organism causes Giardiasis?

Back 68

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 69

69. What is the pathogenesis of Giardiasis?

Back 69

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 70

70. What causes the transition from trophozoites to cysts?

Back 70

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 71

71. Why is Giardia toxigenic?

Back 71

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 72

72. What mediates immunity in Giardia?

Back 72

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

Front 73

73. What is the morphology of Giardiasis?

Back 73

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 74

74. What are the clinical features of Giardiasis?

Back 74

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 75

75. What is necrotizing enterocolitis?

Back 75

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 76

76. What is collagenous colitis?

Back 76

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. Primarily affects middle aged and older women.

Front 77

77. What is lymphocytic colitis?

Back 77

Lymphocytic colitis is characterized by chronic watery diarrhea and a prominent intraepithelial infiltrate of lymphocytes. Affects males and females equally.

Front 78

78. What is AIDS enteropathy?

Back 78

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 79

79. Transplantations and GI issues...

Back 79

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 80

80. What is drug induced intestinal injury?

Back 80

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 81

81. What is radiation enterocolitis?

Back 81

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 82

82. What is neutropenic colitis (typhlitis)

Back 82

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 83

83. What is diversion colitis?

Back 83

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 84

84. What is solitary rectal ulcer syndrome?

Back 84

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 85

85. What are enteropathogenic E. coli (EPEC), and how are they active in infections?

Back 85

Enteropathogenic E. coli (EPEC) do not appear to make any toxins.

They do produce bundle forming pili (Bfp), intimin (an adhesin) and an associated protein (translocated intimin receptor, Tir).

These virulence factors allow bacterial attachment to epithelial cells of the small intestine, leading to disruption of the microvillus (an attaching-effacing) mechanism of action, leading to diarrhea.

Also, these strains belong to particular O serotypes.

Front 86

86. What are enterotoxigenic E. coli (ETEC), and how are they active in infections?

Back 86

Enterotoxigenic E. coli (ETEC) possess colonization factors (fimbrial adhesins).

These bind bacteria to specific receptors on the cell membrane of the small intestine. These organisms produce powerful plasmid-associated enterotoxins which are characterized as being either heat labile (LT) or heat stable (ST).

*Most important bacterial cause of diarrhea in children in resource poor countries. It is also the most common cause of traveler's diarrhea.

Front 87

87. What are enterohemorrhagic E. coli (EHEC), and how are they active in infections?

Back 87

Enterohemorrhagic E. coli (EHEC) isolates produce a verotoxin.

The verotoxin is essentially identical to Shiga toxin. The toxin has a direct effect on intestinal epithelium, resulting in diarrhea.

EHEC causes hemorrhagic colitis and hemolytic-uremic syndrome.

*Serotype O157:H7 is the most important in human infections.

Front 88

88. What are enteroinvasive E. coli (EIEC), and how are they active in infections?

Back 88

Enteroinvasive E. coli (EIEC) attach specifically to the mucosa of the large intestine.

They invade cells by endocytosis by using plasmid-associated genes. Inside the cell, they lyse the endocytic vacuole, multiply and spread to ajacent cells, causing tissue destruction, inflammation, necrosis, and ulceration, resulting in blood and mucus in the stools.

*It is an important cause of diarrhea in areas of poor hygiene.

Front 89

89. What are enteroaggregative E. coli (EAEC), and how are they active in infections?

Back 89

Enteroaggregative E. coli (EAEC) derive their name from their characteristic attachment pattern to tissue culture cells.

The pattern is an aggregative or 'stacked brick' formation. These organisms act in the small intestine to cause persistent diarrhea especially in children in resource poor countries.

*Their aggregative adherence ability is due to plasmid associated fimbriae. EAEC also produce heat-labile toxins.

Front 90

90. What are diffuse-aggregative E. coli (DAEC), and how are they active in infections?

Back 90

Diffuse-aggregative E. coli (DAEC) produce an alpha hemolysin and cytotoxic necrotizing factor 1.

They are also known as diffuse-adherent or cell-detaching E. coli.

Front 91

91. Which strains of E. coli are the most important contributor to global incidence of diarrhea?

Back 91

EPEC and ETEC are the most important contributors to global incidence of diarrhea.

EHEC O157:H7 is more important in resource-rich countries.

Front 92

92. What organism is the most common cause of food-associated diarrhea in many resource rich countries?

Back 92

Salmonella.

There is a large animal reservoir of infection, which is transmitted to humans via contaminated food, especially poultry and diary products. It is also transmitted from person-to-person via contaminated preparation of food.

Front 93

93. How is salmonella acquired?

Back 93

Via oral consumption food or drink that is contaminated.

Initial entry is probably thru uptake by M cells (the 'antigenic samplers' of the bowel) with subsequent spread to epithelial cells.

The bacteria migrate to the ileocecal region, where their multiplication stimulates an inflammatory response, which causes the release of prostaglandins. These in turn activate cAMP and fluid secretion, resulting in diarrhea.

Front 94

94. What species of salmonella may become invasive?

Back 94

S. enteritidis, S. choleraesuis may become invasive in patients w/particular predispositions.

The organisms are not contained w/in the GI tract, but invade the body to cause septicemia; consequently, many organs become seeded w/salmonellae, sometimes leading to osteomyelitis, pneumonia, or meningitis.

Front 95

95. What is campylobacteri?

Back 95

Campylobacter spp. are curved or S-shaped gram-negative rods that are among the commonest causes of diarrhea.

They require special culture media b/c they are microaerophilic and thermophilic.

There is a large animal reservoir in cattle, sheep, rodents, poultry, and wild birds. Infections are acquired by consumption of contaminated food, especially poultry, milk, or water. (Birds pecking at baby bottles)

Front 96

96. What treatment is used for severe Campylobacter diarrhea?

Back 96

Macrolide antibiotic such as erythromycin can be used in diarrheal disease that is severe enough to warrant treatment.

Invasive infections may require treatment w/an additional antibiotic such as quinolone or an aminoglycoside.

Front 97

97. What is cholera?

Back 97

Cholera is an acute infection of the GI tract caused by the comma-shaped rod Gram-negative bacterium V. cholerae.

Cholera flourishes in communities with inadequate clean drinking water and sewage disposal. It is a free-living inhabitant of fresh water, but causes infections only in humans. The disease is spread via contaminated food (i.e. shellfish).

Front 98

98. What are the V. cholerae serotypes based on?

What is the El tor biotype?

Back 98

V. cholerae serotypes are based on somatic O antigens.

Serotype O1 is the most important and is divided into two biotypes: classical and El tor.

The El tor biotype differs from classical V. cholera in several ways. In particular, it causes only a mild diarrhea and has a higher ratio of carriers to cases; carriage is also more prolonged, and the organisms survive better in the environment.

Front 99

99. What is the O139 strain?

Back 99

A new non-O1 strain (O139) appears to have originated from the El tor O1 biotype when the latter acquired a new O (capsular) antigen by horizontal gene transfer from a non-O1 strain.

This provided the recipient strain w/a selective advantage in a region where a large part of the population was immune to O1 strains.

Front 100

100. What causes the symptoms of cholera?

What are the 3 virulence factors?

Back 100

The enterotoxin produced by cholerae in the GI tract.

Virulence factors include:
1. Motility (polar flagella)
2. Production of mucinase
3. Attachment to specific receptors

Front 101

101. What is Shigellosis?

Back 101

AKA bacillary dysentery because in its more severe form it is characterized by an invasive infection of the mucosa of the large intestine causing inflammation and resulting in the presence of pus and blood in the diarrheal stool.

However, symptoms range from mild to severe depending upon the species of Shigella involved and on the underlying state of health of the host

Front 102

102. What are the four different types of Shigella species?

Which is the most serious?

Back 102

1. Shigella sonnei causes most infections at the mild end of the spectrum

2. Shigella flexneri and S. boydii usually produce more severe disease

3. Shigella dysenteriae is the most serious.

Front 103

103. How is Shigellosis acquired/spread?

Back 103

Shigellosis is primarily a pediatric disease. When associated with severe malnutrition it may precipitate complications such as the protein deficiency syndrome 'kwashiorkor'.

Like V. cholerae, shigellae are human pathogens without an animal reservoir, but unlike the vibrios, they are not found in the environment, being spread from person to person by the fecal-oral route and less frequently by contaminated food and water.

Shigellae appear to be able to initiate infection from a small infective dose (10-100 organisms) and therefore spread is easy in situations where sanitation or personal hygiene may be poor (e.g. refugee camps, nurseries, day-care centers and other residential institutions).

Front 104

104. How does Shigella cause infection?

Back 104

Shigella diarrhea is usually watery at first, but later contains mucus and blood Shigellae attach to, and invade, the mucosal epithelium of the distal ileum and colon, causing inflammation and ulceration. However, they rarely invade through the gut wall to the bloodstream.

S. dysenteriae produce a (Shiga) toxin similar to that associated with enterohemorrhagic E. coli (EHEC), which can cause damage to the intestinal epithelium and glomerular endothelial cells, the latter leading to kidney failure (hemolytic-uremic syndrome,

Front 105

105. What are the symptoms of Shigellosis?

Back 105

Diarrhea is usually watery initially, but later contains mucus and blood. Lower abdominal cramps can be severe. The disease is usually self-limiting, but dehydration can occur, especially in the young and elderly. Complications can be associated with malnutrition.

Front 106

106. How is Shigella diarrhea treated?

Back 106

Antiobiotics should only be given for severe diarrhea.

Rehydration may be indicated. Antibiotics, especially those that also decrease intestinal motility, should not be given except in severe cases. Plasmid-mediated resistance is common, and antibiotic susceptibility tests should be performed on shigella isolates if treatment is required.

Front 107

107. Summary of bacterial causes of diarrhea

Back 107

Salmonella and Campylobacter infections and some types of E. coli infections are most often food-associated, whereas cholera is more often water-borne, and shigellosis is usually spread by direct fecal-oral contact.

Front 108

108. What is V. parahaemolyticus?

Back 108

V. parahaemolyticus is a halophilic (salt-loving) vibrio that contaminates seafood and fish. If these foods are consumed uncooked, diarrheal disease can result.

The mechanism of pathogenesis is still unclear. Most strains associated with infection are hemolytic due to production of a heat-stable cytotoxin and have been shown to invade intestinal cells (in contrast to V. cholerae, which is non-invasive and cholera toxin, which is not cytotoxic).

Front 109

109. What is Yersinia enterocolitica?

Back 109

Yersinia enterocolitica is a member of the Enterobacteriaceae and is a cause of food-associated infection especially among infants and particularly in colder parts of the world. The reason for this geographic distribution is unknown, but it has been speculated that it is because the organism prefers to grow at temperatures of 22-25°C.

Front 110

110. Where is Y. enterocolitica found and how does it spread?

Back 110

Y. enterocolitica is found in a variety of animal hosts including rodents, rabbits, pigs, sheep, cattle, horses and domestic pets.

Transmission to humans from household dogs has been reported. The organism survives and multiplies, albeit more slowly, at refrigeration temperatures (48°C) and has been implicated in outbreaks of infection associated with contaminated milk as well as other foods.

Front 111

111. What are the symptoms of Y. enterocolitica infection?

Back 111

The mechanism of pathogenesis is unknown, but the clinical features of the disease result from invasion of the terminal ileum, necrosis in Peyer's patches and an associated inflammation of the mesenteric lymph nodes.

The presentation, with enterocolitis and often mesenteric adenitis, can easily be confused with acute appendicitis, particularly in children.

Front 112

112. What are two spore-forming gram-positive species that cause diarrhea?

Back 112

1. Clostridum perfringens
2. Bacillus cereus

Front 113

113. What is Clostridum perfringens?

Back 113

Cl. perfringens is associated with diarrheal diseases in different circumstances, common and rare

The common are the enterotoxin-producing type A strains; the rare are the β-toxin-producing strains.

Front 114

114. What are the β-toxin-producing strains ?

Back 114

•Much more rarely, β-toxin-producing strains produce an acute necrotizing disease of the small intestine, accompanied by abdominal pain and diarrhea. This form occurs after the consumption of contaminated meat by people who are unaccustomed to a high protein diet and do not have sufficient intestinal trypsin to destroy the toxin. It is traditionally associated with the orgiastic pig feasts enjoyed by the natives of New Guinea, but also occurred in people released from prisoner of war camps.

Enterotoxin production can be demonstrated by a latex agglutination method.

Front 115

115. What is bacillus cereus?

What are the two forms of infection?

Back 115

Bacillus cereus spores and vegetative cells contaminate many foods, and food-associated infection takes one of two forms:
1. diarrhea resulting from the production of enterotoxin in the gut
2. vomiting due to the ingestion of enterotoxin in food.

Two different toxins are involved, one in rice and pulses; the other in various foods.

Front 116

116. What is Clostridium difficile?

What causes it?

Back 116

Clostridium difficile infection is the most commonly diagnosed bacterial cause of hospital-acquired infectious diarrhea in resource-rich countries.

Clindamycin is not the cause of the condition; it merely inhibits the normal gut flora and allows Cl. difficile to multiply.

Front 117

117. What are the features of C. difficile?

Back 117

This organism is commonly found in the gut of children and to a lesser extent in adults, but can also be acquired from other patients in hospital by cross-infection.

Cl difficile is a spore former and survives in the environment as it is resistant to heat and acid, for example. The spores contaminate the environment and become vegetative bacteria that can be transmitted between patients on the wards.

In common with other clostridia, Cl. difficile produces exotoxins, two of which have been characterized: one is a cytotoxin and the other an enterotoxin, that cause hemostasis and tissue necrosis in the colon, resulting in diarrhea.

Front 118

118. What are the two toxins produced by C. difficile?

Back 118

Toxin A and toxin B are encoded within a short chromosomal segment carried by pathogenic strains of Cl. difficile, referred to as the pathogenicity locus, as is a regulatory gene tcdC. There is also a binary toxin encoded by two chromosomal genes separate from the chromosomal pathogenicity locus.

One gene mediates cell surface binding and intracellular translocation and the other causes cell death.

Front 119

119. What is the importance of C. difficile 027?

Back 119

An emergent epidemic Cl. difficile variant strain called Cl. difficile 027 has been shown to produce more toxin A and toxin B than most hospital strains. A study reported that the binary toxin genes were associated with partial deletions in the tcdC gene that downregulates the toxin A and B genes, and that severe Cl. difficile-associated diarrhea was significantly associated with them. Finally, Cl. difficile 027 was associated with much higher levels of toxins A and B than in other strains.

It has been associated with higher case fatality rates, with some infected individuals requiring a colectomy and intensive care unit support, and also shown to be more resistant to the fluoroquinolone antibiotics than other strains.

Front 120

120. What is the rotavirus?

Back 120

These are morphologically characteristic viruses. The replicating rotavirus causes diarrhea by damaging transport mechanisms in the gut.

Different rotaviruses infect the young of many mammals, including children, kittens, puppies, calves, foals and piglets, but it is thought that viruses from one host species occasionally cross-infect another.

Front 121

121. What are the features of rotavirus infection?

Back 121

The incubation period is 1-2 days. After virus replication in intestinal epithelial cells there is an acute onset of vomiting, which is sometimes projectile, and diarrhea which lasts from 4 to 7 days. The replicating virus damages transport mechanisms in the gut, and loss of water, salt and glucose causes diarrhea.

Infected cells in the intestine are destroyed, resulting in villous atrophy. The villi, long finger-like projections, become flattened resulting in the loss of both the surface area for absorption and the digestive enzymes, and raised osmotic pressure in the gut lumen causes diarrhea.

There is no inflammation or loss of blood. Exceedingly large numbers of virus particles, 10^10-10^11/g, appear in the feces. For unknown reasons, respiratory symptoms such as cough and coryza are quite common. The disease is more severe in infants in resource-poor countries.

Front 122

122. Who are most susceptible to rotavirus infection?

Back 122

Infection is commonest in children under 2 years of age, and has a seasonal pattern, being most frequent in the cooler months of the year in temperate climates.

IgA antibodies in colostrum give protection during the first 6 months of life. Outbreaks are sometimes seen in nurseries.

Older children are less susceptible to infection, nearly all of them having developed antibodies, but occasional infections occur in adults.

Front 123

123. What are calciviruses?

Back 123

Caliciviruses are 27nm diameter, single-stranded RNA viruses that may cause 'winter vomiting disease'. They include the noroviruses, previously known as the small round structured viruses (SRSV) or Norwalk-like viruses (NLV).

Infection is common in older children and adults. These viruses are highly infectious, spread rapidly and nosocomial infection is common. In up to 50% of cases there may be chills, headache, myalgia or fever as well as nausea, abdominal pain, vomiting and diarrhea, but recovery occurs within 24-48 h.

Front 124

124. How do noroviruses cause infection?

Back 124

Noroviruses bind to cell surface carbohydrates of the ABH histo-blood group antigens and some strains have different binding affinities for different patterns of these antigens. In addition, these antigens are expressed to varying degrees in different individuals, resulting in some people being resistant to infection with specific norovirus strains.

In particular, the noroviruses are a major cause of gastroenteritis in healthcare settings and many outbreaks have been reported in crowded environments such as cruise ships. Noroviruses show a high level of variability resulting in both limited cross protection between strains and reduced immunity in the population. In addition, due to this diversity diagnostic assays have to be modified in order to optimize detection, and vaccine design either has to involve a cross protective component or the development of a multivalent vaccine.

Front 125

125. What are astroviruses?

Back 125

Astroviruses are 28 nm single-stranded RNA viruses of which five serotypes are known and have characteristic five- or six-pointed star patterns. Most infections occur in childhood and are mild.

Front 126

126. What are adenoviruses?

Which two types cause gastroenteritis?

Back 126

Adenoviruses are unenveloped, 70-80 nm double-stranded DNA viruses of which types 40 and 41 are associated with gastroenteritis.

Types 40 and 41 can only be grown in specialized cell culture lines. They are second to rotaviruses as a cause of acute diarrhea in young children in temperate climates.

Front 127

127. How many enterotoxins are produced by Staph aureus?

Back 127

At least eight serologically distinct enterotoxins are produced by strains of Staph. aureus, the best understood of which are enterotoxins A-E.

All are heat stable and resistant to destruction by enzymes in the stomach and small intestine.

They generally behave as superantigens, binding to major histocompatibility complex (MHC) class II molecules, which results in T-cell stimulation.

Their effect on the central nervous system results in severe vomiting within 3-6 h of consumption. Diarrhea is not a feature, and recovery within 24 h is usual.

Front 128

128. How do Staph aureus strains cause infection and spread?

Back 128

Up to 50% of Staph. aureus strains produce enterotoxin, and food (especially processed meats) is contaminated by human carriers.

The bacteria grow at room temperature and release toxin. Subsequent heating may kill the organisms, but the toxin is stable.

Often there are no viable organisms detectable in the food consumed, but enterotoxin can be detected by a latex agglutination test.

Front 129

129. Which strain of Staph aureus is most common in food-associated disease?

Back 129

Enterotoxin A is by far the most common in food associated disease.

Front 130

130. What is Bl. botulinum?

Back 130

Exotoxins produced by Cl. botulinum cause botulism

The organism is widespread in the environment, and spores can be isolated readily from soil samples and from various animals including fish.

Seven serologically distinct toxins have been identified, but only four: A, B, E, and less frequently F, are associated with human disease.

While not destroyed by digestive enzymes, the toxins are inactivated after 30 min at 80°C. The toxins are ingested in food (often canned or reheated) or produced in the gut after ingestion of the organism; they are absorbed from the gut into the bloodstream and then reach their site of action, the peripheral nerve synapses. The action of the toxin is to block neurotransmission.

Front 131

131. What are the three forms of botulism?

Which is most common?

Back 131

1. food-borne botulism
2. infant botulism*
3. wound botulism

*most common

Front 132

132. What are the features of botulism?

Back 132

The clinical disease is the same in all three forms and is characterized by flaccid paralysis leading to progressive muscle weakness and respiratory arrest.

Intensive supportive treatment is urgently required, and complete recovery may take many months. Improvements in supportive care have reduced the mortality from around 70% to approximately 10%, but the disease, although rare, remains life-threatening.

Front 133

133. How is botulism detected?

Back 133

Laboratory diagnosis depends largely upon demonstrating the presence of toxin by injecting samples of feces and food (if available) into mice that have been protected with botulinum antitoxin or left unprotected.

Culture of feces or wound exudate for Cl. botulinum should also be performed.

Front 134

134. What is another supportive therapy for botulinum toxins?

Back 134

Polyvalent antitoxin is recommended as an adjunct to intensive supportive therapy for botulism.

Since botulinum toxins are antigenic, they can be inactivated and used to produce antitoxin in animals. When botulism is suspected, antitoxin should be promptly administered along with supportive care, which may include mechanical ventilation (due to difficulty in breathing) and intravenous and nasogastric nutritional support (due to difficulty in swallowing).

Front 135

135. Why is H. pylori important?

Back 135

The Gram-negative spiral bacterium H. pylori is associated with over 90% of duodenal ulcers and 70-80% of gastric ulcers.

Diagnosis is usually made on the basis of histologic examination of biopsy specimens, although the non-invasive urea breath test (H. pylori produces large amounts of urease) is the most rapid means of detecting the organism's presence. Fecal Helicobacter pylori antigen testing is another non-invasive test. H. pylori can be cultured in the laboratory, but is difficult to grow.

Front 136

136. What is the mechanism of action of H. pylori?

Back 136

The mechanism of pathogenicity is still being elucidated but involves a number of virulence factors, including a cytotoxin, acid-inhibiting protein, adhesins, urease (which aids survival in the acidic environment) and other factors which disrupt the gastric mucosa.

Front 137

137. How is H. pylori treated?

Back 137

Eradication of H. pylori to promote the remission and healing of ulcers requires combination therapy such as a proton pump inhibitor and two antibiotics such as clarithromycin and amoxicillin

Front 138

138. What are the differing features of parasitic infections?

Back 138

In general, the stages of protozoan parasites passed in feces are either already infective or become infective within a short time. These parasites are therefore usually acquired by swallowing infective stages in fecally contaminated food or water.

Worm parasites, with two major exceptions (pinworm and the dwarf tapeworm), produce eggs or larvae that require a period of development outside the host before they become infective.

Front 139

139. What are the three protazoan infective parasites?

Back 139

•Entamoeba histolytica
•Giardia lamblia
•Cryptosporidium parvum

All three can give rise to diarrheal illnesses, but the organisms have distinctive features that allow a differential diagnosis to be made quite easily. Other intestinal protozoa of concern, particularly in immunosuppressed patients, include Cyclospora cayetanensis, Isospora belli and the microsporidia.

Front 140

140. What is Entamoeba histolytica?

Back 140

Entamoeba histolytica infection is particularly common in subtropical and tropical countries.

The trophozoite stages of the amebae live in the large intestine on the mucosal surface. Reproduction of these stages is by simple binary fission, and there is periodic formation of resistant encysted forms, which pass out of the body. These cysts can survive in the external environment and act as the infective stages.

Front 141

141. How does E. histolytica infection occur and spread?

Back 141

Infection occurs when food or drink is contaminated either by infected food handlers or as a result of inadequate sanitation.

Transmission can also take place as a result of anal sexual activity. The cysts pass intact through the stomach when swallowed and excyst in the small intestine, each giving rise to eight progeny. These adhere to the epithelial cells and damage them by phagocytosis and cytolysis. They can invade the mucosa and feed on host tissues including red blood cells, giving rise to amebic colitis.

Front 142

142. What are the symptoms of E. histolytica?

Back 142

E. histolytica infection may cause mild diarrhea or severe dysentery.

Invasion of the mucosa by E. histolytica may produce small localized superficial ulcers or involve the entire colonic mucosa with the formation of deep confluent ulcers.

Complications include perforation of the intestine, leading to peritonitis, and extraintestinal invasion. Trophozoites can spread via the blood to the liver, with the formation of an abscess, and may secondarily extend to the lung and other organs. Rarely, abscesses spread directly and involve the overlying skin.

Front 143

143. How is E. histolytica infection diagnosed?

How is it treated?

Back 143

E. histolytica infection can be diagnosed in asymptomatic patients from the presence of characteristic four-nucleate cysts in the stool.

Acute E. histolytica infection can be treated with metronidazole.

Front 144

144. What is giardia lamblia?

Back 144

Giardia has a global distribution and is a frequent cause of traveler's diarrhea. Giardia is the most commonly diagnosed intestinal parasite in the USA, having been detected in both drinking and recreational water

Front 145

145. What is the life-cycle of giardia?

Back 145

The two life cycle stages are the flagellate (four pairs of flagella) binucleate trophozoite and the resistant four-nucleate cyst. The trophozoites live in the upper portion of the small intestine, adhering closely to the brush border of the epithelial cells by specialized attachment regions.

They divide by binary fission and can occur in such numbers that they cover large areas of the mucosal surface. Cyst formation occurs at regular intervals, each cyst being formed as one trophozoite rounds up and produces a resistant wall.

Cysts pass out in the stools and can survive for several weeks under optimum conditions. Infection occurs when the cysts are swallowed, usually as a result of drinking contaminated water. The minimum infective dose is very small: 10-25 cysts.

Front 146

146. How is giardia spread?

Back 146

Epidemics of giardiasis have occurred when public drinking supplies have become contaminated, but smaller outbreaks have been traced to drinking from rivers and streams that have been contaminated by wild animals.

Apart from water-borne transmission, Giardia can be passed from person to person, especially within families, with food-borne transmission being rare.

Giardia may also be transmitted sexually among homosexual men.

The genus Giardia is widely distributed in mammals, and there is suggestive evidence for cross-infection between certain animal hosts (e.g. beaver) and humans.

Front 147

147. What are the symptoms of giardia infection?

Back 147

The diarrhea may be:
•self-limiting, with 7-10 days being the usual course
•chronic, and develop into a serious condition, particularly in patients with deficient or compromised immunologic defenses.

It is thought to arise from inflammatory responses triggered by the damaged epithelial cells and from interference with normal absorptive processes.

Characteristically the stools are loose, foul-smelling and often fatty.

Front 148

148. How is giardia treated?

Back 148

Giardia infection can be treated with a variety of drugs. These include mepacrine hydrochloride, metronidazole and tinidazole, but none is completely successful.

Front 149

149. What is Cryptosporidium parvum?

Back 149

There are two major genotypes, one associated with human infection, one primarily with animals (including cattle), but cross-infection to humans does occur.

The parasite has a complex life cycle, going through both asexual and sexual phases of development in the same host.

Transmission requires ingestion of a minimum of 10 or so of the resistant oocyst stage (4-5 mm diameter) in fecally contaminated material. In the small intestine, the cyst releases infective sporozoites, which invade the epithelial cells, remaining closely associated with the apical plasma membrane. Here they form schizonts, which divide to release merozoites, and these then re-invade further epithelial cells.

Eventually a sexual phase occurs and oocysts are released. Transmission probably occurs most often via drinking water contaminated by oocysts, either from other humans or from animals.

Front 150

150. What are the symptoms of C. parvum?

Back 150

Symptoms of infection with C. parvum range from a moderate diarrhea to a more severe profuse diarrhea that is self-limiting in immunocompetent individuals (lasting 15-40 days), but can become chronic in immunocompromised patients.

Cryptosporidiosis is a common infection in people with AIDS. In individuals with CD4+ T-cell counts <100/mm^3 diarrhea is prolonged, may become irreversible, and can be life-threatening.

Front 151

151. What is the treatment for C. parvum?

Back 151

Routine fecal examinations are inadequate for diagnosing C. parvum diarrhea. Concentration techniques and special staining (e.g. modified Ziehl-Neelsen stain) are necessary to recover and identify the oocysts.

*Only immunocompromised patients need treatment for C. parvum diarrhea.

Highly active antiretroviral therapy (HAART) in individuals with AIDS infected with C. parvum has been reported to improve the diarrhea symptoms. This may be due to the protease inhibitors used in combination therapy interfering directly with the C. parvum proteases involved in the protozoal life cycle. In addition, HAART results in lowering the HIV load and immune reconstitution.

Front 152

152. What is cyclospora cayetanensis?

Back 152

Cyclospora cayetanensis, identified in 1994, is one of the causes of traveler's diarrhea.

It can also be acquired from contaminated imported food; for example, Guatemalan raspberries were thought to be the cause of an outbreak in the USA in 1997.

Diarrhea can be prolonged and is severe in immunosuppressed individuals. Trimethoprim-sulfamethoxazole (co-trimoxazole) treatment is effective.

Front 153

153. What is Isospora belli?

What other infections with microsporidia are a cause of diarrhea in AIDS and other immunosuppressed patients?

Back 153

AIDS patients infected with Isospora belli may show particularly severe symptoms, persistent diarrhea causing weight loss and even death.

Infections with microsporidia, an unusual group, have also become recognized as a cause of diarrhea in AIDS and other immunosuppressed patients. Enterozoon bieneusi is the commonest cause, although Encephalitozoon intestinalis also occurs. Transmission appears to be direct. Albendazole and metronidazole have been used successfully to treat infections.

Front 154

154. What are the most clinically important intestinal worms?

Back 154

The most important intestinal worms clinically are the nematodes known as 'soil-transmitted helminths'.

There are two groups:
•Ascaris lumbricoides (large roundworm) and Trichuris trichiura (whipworm), in which infection occurs by swallowing the infective eggs
•Ancylostoma duodenale and Necator americanus (hookworms) and Strongyloides stercoralis, which infect by active skin penetration by infective larvae, that then undertake a systemic migration through the lungs to the intestine.

Front 155

155. What is Enterobius vermicularis?

Back 155

The pinworm or threadworm Enterobius vermicularis is perhaps the commonest intestinal nematode in resource-rich countries and is the least pathogenic. The females of this species, which live in the large bowel, release infective eggs onto the perianal skin. This causes itching, and transmission usually occurs directly from contaminated fingers, but the eggs are also light enough to be carried in dust.

Front 156

156. Where do female Ascaris and Trichuris lay their eggs?

Back 156

Female Ascaris and Trichuris lay thick-shelled eggs in the intestine, which are expelled with feces and hatch after being swallowed by another host.

Front 157

157. Where do adult female hookworms lay their eggs?

Back 157

Adult female hookworms lay thin-shelled eggs that hatch in the feces shortly after leaving the host.

The larvae of these hookworms (A. duodenale and N. americanus) feed on bacteria until infective, and then migrate away from the fecal mass.

Infection takes place when larvae come into contact with unprotected skin (or additionally, in the case of Ancylostoma, are swallowed). They penetrate the skin, migrate via the blood to the lungs, climb the trachea and are swallowed. Adult worms attach by their enlarged mouths to the intestinal mucosa, ingest a plug of tissue, rupture capillaries and suck blood.

Front 158

158. What are the important features of the Strongyloides?

Back 158

The life cycle of Strongyloides is similar to that of hookworms, but shows some important differences. The adult worm exists as a parthenogenetic female that lays eggs into the mucosa. These eggs hatch in the intestine and the released larvae usually pass out in the feces.

Development outside the host can follow the hookworm pattern, with the direct production of skin-penetrating larvae, or may be diverted into the production of a complete free-living generation, which then produces infective larvae. Under certain conditions, and particularly when the host is immunocompromised, Strongyloides larvae can re-invade before they are voided in the feces. This process of autoinfection can give rise to the severe clinical condition known as disseminated strongyloidiasis. All soil-transmitted helminths are relatively long-lived (several months to years), but authenticated cases show that Strongyloides infections can persist for more than 30 years, presumably through continuous internal autoinfection.

Front 159

159. Large numbers of adult Ascaris worms can lead to...?

Back 159

Intestinal obstruction

Large numbers of adult worms can cause a physical blockage in the intestine, and this may also occur as worms die following chemotherapy. Intestinal worms tend to migrate out of the intestine, often up the bile duct, causing cholangitis. Perforation of the intestinal wall can also occur.

Front 160

160. Moderate to severe Trichuris infection can cause...

Back 160

Chronic diarrhea which can lead to impaired nutrition and retarded growth.

Occasionally, heavy infections lead to prolapse of the rectum.

Front 161

161. Hookworm disease can result in...?

Back 161

Iron-deficiency anemia.

The blood-feeding activities of the intestinal worms can lead to an iron-deficiency anemia if the diet is inadequate. Heavy infections cause a marked debility and growth retardation.

Front 162

162. What is the treatment for intestinal nematodes?

Back 162

A variety of anthelmintic drugs is available for treating intestinal nematodes. Piperazine has been used with great success against Ascaris, hookworms and pinworm, though other drugs such as albendazole, mebendazole, levamisole and pyrantel can also be used and are also effective against trichuriasis and strongyloidiasis (especially albendazole and levamisole).

At the community level, prevention can be achieved through improved hygiene and sanitation, making sure that fecal material is disposed of properly.

Front 163

163. What is Taenia saginata?

Back 163

The beef tapeworm Taenia saginata, transmitted through infected beef, is the most widely distributed. However, infection is usually asymptomatic, apart from the nausea felt on passing the large segments. Diagnosis involves finding these segments or the characteristic eggs in the stool.

Front 164

164. What is Diphyllobothrium latum?

Back 164

Diphyllobothrium latum, the broadfish tapeworm, is widely distributed geographically, but infection is restricted to individuals eating raw or undercooked fish carrying the infective larvae. The eggs of this species have a terminal 'lid' and are the diagnostic stage in the stool.

Front 165

165. What is Hymenolepsis nana?

Back 165

Hymenolepis nana, the dwarf tapeworm, occurs primarily in children, infection occurring directly by swallowing eggs.

This worm has the ability to undergo autoinfection within the host's intestine, so that a large number of worms can build up rapidly, leading to diarrhea and some abdominal discomfort.

Front 166

166. What is Listeria infection?

How does it present?

Back 166

Listeria infection is associated with pregnancy and reduced immunity.

Listeria monocytogenes is a Gram-positive coccobacillus that is widespread among animals and in the environment. It is a food-borne pathogen, associated particularly with uncooked foods such as paté, contaminated milk, soft cheeses and coleslaw.

*The disease usually presents as meningitis.

Front 167

167. HepA virus

Back 167

Hepatitis A (HAV)

Class: Hepatovirus
Type: ssRNA
Transmission: Fecal-oral
Incubation: 2-4 weeks
Notes: No carrier state. Clinically, hepatitis A is milder in young children than in older children and adults

Front 168

168. HepB virus

Back 168

Hepatitis B (HBV)

Class: Hepadnavirus
Type: dsDNA
Transmission: Blood-borne, sexual
Incubation: 6 weeks-6 months
Notes: Carriage associated with liver cancer; HB surface antigen can be found in blood and other body fluids; HBV is not directly cytopathic for liver cells, and the pathology is largely immune mediated; Certain groups of people are more likely to become carriers of hepatitis B (immunodeficient); Complications of hepatitis B are cirrhosis and hepatocellular carcinoma; Hepatitis B infection can be prevented by immunization.

Front 169

169. HepC virus

Back 169

Hepatitis C (HCV)

Class: Flavivirus
Type: ssRNA
Transmission: blood-borne
Incubation: 2 months
Notes: carriage associated w/liver CA; Hepatitis C virus is the commonest cause of transfusion-associated hepatitis; About 75-85% of HCV-infected individuals develop chronic HCV; Treatment with pegylated IFNα and ribavirin is the standard of care

Front 170

170. HepD virus

Back 170

Hepatitis D (HDV)

Class: Deltavirus
Type: ssRNA
Transmission: from blood
Incubation: 2-12 weeks
Notes: Needs concurrent HepB virus infection

Front 171

171. HepE virus

Back 171

Hepatitis E (HEV)

Class: Calcivirus
Type: ssRNA
Transmission: fecal-oral
Incubation: 6-8 weeks
Notes: Common in far East; no carrier state

Front 172

172. Yellow fever

Back 172

Yellow fever

Class: Flavivirus
Type: ssRNA
Transmission: Mosquito
Incubation: 3-6 days
Notes: no person-person spread; no carrier state.

Front 173

173. What does Schistosoma mansoni infection result in?

Back 173

Inflammatory responses to the eggs of Schistosoma mansoni result in severe liver damage.

Although the worms spend only a relatively short time in the liver before moving to the mesenteric vessels, eggs released by the females can be swept by the bloodstream into the hepatic circulation and be filtered out in the sinusoids. The inflammatory response to these trapped eggs is the primary cause of the complex changes that result in hepatomegaly, fibrosis and the formation of varices

Front 174

174. What is the liver fluke Clonorchis sinensis?

Back 174

In Asia, infections with the human liver fluke Clonorchis sinensis are acquired by eating fish infected with the metacercarial stage.

Juvenile flukes released in the intestine move up the bile duct and attach to the duct epithelium, feeding on the cells and blood and tissue fluids.

In heavy infections, there is a pronounced inflammatory response, and proliferation and hyperplasia of the biliary epithelium, cholangitis, jaundice and liver enlargement are possible consequences. There may be an association with cholangiocarcinoma, but there is little evidence for this in humans

Front 175

175. What is Echinococcus granulosus?

Back 175

The larval stages of the dog tapeworm Echinococcus granulosus can develop in humans when the eggs are swallowed. Larvae from the eggs move from the intestine into the body and frequently develop into large hydatid cysts in the liver. These can be diagnosed on scans as large cavities.

Apart from pressure damage to surrounding tissues, rupture of the cysts leads to secondary cysts and may cause anaphylaxis. Lesions caused by E. granulosus in hydatid disease can become secondarily infected with bacteria. The source of infection may be local to the lesion or another body site, but is usually undiagnosed.

Cysts can be removed surgically or treated with benzimidazole drugs.

Front 176

176. What is a feature of E. histolytica liver abscesses?

Back 176

Despite its name an amebic liver abscess does not consist of pus.

Front 177

177. What organisms cause spontaneous bacterial peritonitis (SBP)?

Back 177

Spontaneous bacterial peritonitis (SBP) is most commonly associated with cirrhosis of the liver. SBP is typically due to Gram-negative enteric bacteria, most commonly E. coli.

Front 178

178. What organisms cause secondary peritonitis?

Back 178

Secondary peritonitis and intra-abdominal abscesses more often involve a mixture of organisms, especially the Gram-negative anaerobe Bacteroides fragilis.

Mycobacterium tuberculosis and Actinomyces can also cause intraperitoneal infection.