Chapter17: INTESTINES:Infectious Enterocolitis Flashcards

1
Q

Enterocolitis can present with a broad range of symptoms including what?

A

diarrhea, abdominal pain,
urgency, perianal discomfort, incontinence, and hemorrhage
( Table 17-7 ).

This global problem is responsible for more than 12,000 deaths per day among children in developing countries and half of all deaths before age 5 worldwide.

Bacterial infections, such as enterotoxigenic
Escherichia coli, are frequently responsible
, but the most common pathogensvary with age,
nutrition, and host immune status as well as environmental influences
( Table 17-7 ).

For example, epidemics of cholera are common in areas with poor sanitation, as a result of inadequate public health measures, or as a consequence of natural disasters or war.

Pediatric infectious diarrhea, which may result in severe dehydration and metabolic acidosis, is commonly caused by enteric viruses.

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2
Q

TABLE 17-7 – Features of Bacterial Enterocolitides

Infection Type

A
  • Cholera
  • Campylobacter spp.
  • Shigellosis
  • Salmonellosis
  • Enteric (typhoid) fever
  • Yersinia spp.
  • Escherichia coli
    • Enterotoxigenic
      (ETEC)
    • Enterohemorrhagic
      (EHEC)
    • Enteroinvasive (EIEC)
    • Enteroaggregative
      (EAEC)
  • Pseudomembranous
    colitis (C. difficile
  • Whipple disease
  • Mycobacterial infection
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3
Q

TABLE 17-7 – Features of Bacterial Enterocolitides

Geograph

A
  • Cholera: India, Africa
  • Campylobacter spp. :Developed countries
  • Shigellosis : Developing countries
  • Salmonellosis: Worldwide
  • Enteric (typhoid) fever: India, Mexico, Phillipines
  • Yersinia spp. : Northern and central Europe
  • Escherichia coli
    • Enterotoxigenic (ETEC)
      • Developing countries
    • Enterohemorrhagic (EHEC)
      • Worldwide
    • Enteroinvasive (EIEC)
      • Developing countries
    • Enteroaggregative (EAEC)
      • Worldwide
  • Pseudomembranous colitis (C. difficile: colitis (C. difficile): Developing countries
  • Whipple disease: Rural > urban
  • Mycobacterial infection: Worldwide
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4
Q

TABLE 17-7 – Features of Bacterial Enterocolitides

Reservoir

A
  • Cholera: Shellfish
  • Campylobacter spp. Chickens, sheep, pigs, cattle
  • Shigellosis :Humans
  • Salmonellosis: Poultry, farm animals, reptiles
  • Enteric (typhoid) fever: Humans
  • Yersinia spp. : Pigs
  • Escherichia coli
    • Enterotoxigenic (ETEC)
      • Unknown
  • Enterohemorrhagic (EHEC)
    • Widespread, includes cattle
  • Enteroinvasive (EIEC)
    • Unknown
  • Enteroaggregative (EAEC)
    • Unknown
  • Pseudomembranous colitis (C. difficile: colitis (C. difficile):Humans, hospitals
  • Whipple disease: Unknown
  • Mycobacterial infection: Unknown
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5
Q

TABLE 17-7 – Features of Bacterial Enterocolitides

Transmission

A
  • Cholera: Fecal-oral, water
  • Campylobacter spp.: Poultry, milk,
    other foods
  • Shigellosis :Fecal-oral, food, water
  • Salmonellosis: Meat, poultry, eggs, milk
  • Enteric (typhoid) fever: Fecal-oral,
    water
  • Yersinia spp. : Pork, milk, water
  • Escherichia coli
    • Enterotoxigenic (ETEC)
      • Food or fecaloral
    • Enterohemorrhagic (EHEC)
      • Beef, milk, produce
  • Enteroinvasive (EIEC)
    • Cheese, other foods, water
  • Enteroaggregative (EAEC)
    • Unknown
  • Pseudomembranous colitis (C. difficile: colitis (C. difficile):Antibiotics allow emergence
  • Whipple disease: Unknown
  • Mycobacterial infection: Unknown
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6
Q

TABLE 17-7 – Features of Bacterial Enterocolitides

Epidemiology

A
  • Cholera:Sporadic, endemic, epidemic
  • Campylobacter spp.: Sporadic; children, travelers
  • Shigellosis :Children
  • Salmonellosis: Children, elderly
  • Enteric (typhoid) fever: Children. adolescents, travelers
  • Yersinia spp. : Clustered cases
  • Escherichia coli
    • Enterotoxigenic (ETEC)
      • Infants, adolescents, travelers
    • Enterohemorrhagic (EHEC)
      • Sporadic and epidemic
    • Enteroinvasive (EIEC)
      • Young children
    • Enteroaggregative (EAEC)
      • Children, adults, travelers
  • Pseudomembranous colitis (C. difficile: colitis (C. difficile):Immunosuppressed, antibiotic-treated
  • Whipple disease: Rare
  • Mycobacterial infection:Immunosuppressed
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7
Q

TABLE 17-7 – Features of Bacterial Enterocolitides

Affected GI Sites

A
  • Cholera:Small intestine
  • Campylobacter spp.: Sporadic;
  • Shigellosis :Left colon, ileum
  • Salmonellosis: Colon and small intestine
  • Enteric (typhoid) fever: Small intestine
  • Yersinia spp. :Ileum, appendix, right colon
  • Escherichia coli
    • Enterotoxigenic (ETEC)
      • Small intestine
    • Enterohemorrhagic (EHEC)
      • Colon
    • Enteroinvasive (EIEC)
      • Colon
    • Enteroaggregative (EAEC)
      • Colon
  • Pseudomembranous colitis (C. difficile: colitis (C. difficile):Colon
  • Whipple disease: Small intestine
  • Mycobacterial infection:Small intestine
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8
Q

TABLE 17-7 – Features of Bacterial Enterocolitides

Symptoms

A
  • Cholera:Severe watery diarrhea
  • Campylobacter spp.: Watery or bloody diarrhea
  • Shigellosis : Bloody diarrhea
  • Salmonellosis: Watery or bloody diarrhea
  • Enteric (typhoid) fever: Bloody diarrhea, fever
  • Yersinia spp. :Abdominal pain, fever, diarrhea
  • Escherichia coli
    • Enterotoxigenic (ETEC)
      • Severe watery diarrhea
    • ​Enterohemorrhagic (EHEC)
      • Bloody
        diarrhea
    • Enteroinvasive (EIEC)
      • Bloody diarrhea
    • Enteroaggregative (EAEC)
      • Nonbloody diarrhea,afebril
  • Pseudomembranous colitis (C. difficile: colitis (C. difficile):Watery diarrhea, fever
  • Whipple disease: Malabsorption
  • Mycobacterial infection:Malabsorption
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9
Q

TABLE 17-7 – Features of Bacterial Enterocolitides

Complications

A
  • Cholera: Dehydration, electrolyte imbalances
  • Campylobacter spp.: Arthritis, Guillain-Barré syndrome
  • Shigellosis :Reiter syndrome, hemolyticuremic syndrome
  • Salmonellosis: Sepsis, abscess
  • Enteric (typhoid) fever: Chronic infection, carrier state, encephalopathy, myocarditis
  • Yersinia spp. :Autoimmune, e.g., Reiter syndrome
  • Escherichia coliEnterotoxigenic (ETEC)
    • Dehydration, electrolyte imbalances
  • ​Enterohemorrhagic (EHEC)
    • Hemolyticuremic syndrome
  • Enteroinvasive (EIEC)
    • Unknown
  • Enteroaggregative (EAEC)
    • Poorly defined
  • Pseudomembranous colitis (C. difficile: colitis (C. difficile):Relapse
  • Whipple disease: Arthritis, CNS disease
  • Mycobacterial infection:Pneumonia,
    infection at other sites
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10
Q

Describe the Vibrio cholerae.

A

Vibrio cholerae are comma-shaped, Gram-negative bacteria that cause cholera, a disease that
has been endemic in the Ganges Valley of India and Bangladesh for all of recorded history.

Since 1817, seven great pandemics have spread along trade routes to large parts of Europe, Australia, and the Americas, [56] but, for unknown reasons these pandemics resolved and cholera retreated back to the Ganges Valley.

Cholera also persists within the Gulf of Mexico.

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11
Q

What is the MOT of V. cholerae?

A

is primarily transmitted by contaminated drinking water.

However, it can also be present in food and causes sporadic cases of seafood-associated disease in North America.

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12
Q

Why is there a marked seasonal variation of Vibrio cholerae?

A

There is a marked seasonal variation in most climates due to rapid growth of Vibrio bacteria at warm temperatures

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13
Q

What is the only reservoir of V. cholerae?

A

the only animal reservoirs are shellfish and plankton.

Relatively few V. cholerae serotypes are pathogenic, but other species of Vibrio can also cause disease.

For example, V. parahaemolyticus is the most common cause of seafood-associated gastroenteritis
in North America

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14
Q

What is the pathogenesis of V.cholerae?

A

Despite the severe diarrhea, Vibrio organisms are non-invasive and remain within the intestinal
lumen.

A preformed enterotoxin, cholera toxin, encoded by a virulence phage and released by
the Vibrio organism, causes disease, but flagellar proteins, which are involved in motility and
attachment,
arenecessary for efficient bacterial colonization.

Hemagglutinin, a metalloproteinase, is important for bacterial detachment and shedding in the stool.

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15
Q

What is the mechanism that induces diarrhea in Cholerae toxin?

A

The mechanism by which cholera toxin induces diarrhea is well understood ( Fig. 17-27 ).

Cholera toxin is composed of five B subunits and a single A subunit.

The B subunit binds GM1 ganglioside on the surface of intestinal epithelial cells, and is carried by endocytosis to the endoplasmic reticulum, a process called retrograde transport. [58]

Here, the A subunit is reduced by protein disulfide isomerase, and a fragment of the A subunit is unfolded and released.

This peptide fragment is then transported into the cytosol using host cell machinery that moves misfolded proteins from the endoplasmic reticulum to the cytosol.

Such unfolded proteins are normally disposed of via the proteasome, but the A subunit refolds to avoid degradation.

The refolded A subunit peptide then interacts with cytosolic ADP ribosylation factors (ARFs) to ribosylate and activate the stimulatory G protein Gsα.

This stimulates adenylate cyclase and the resulting increases in intracellular cAMP open the cystic fibrosis transmembrane conductance regulator, CFTR, which releases chloride ions into the lumen.

This causes secretion of bicarbonate, sodium, and water, leading to massive diarrhea.

Chloride and sodium absorption are also inhibited by cAMP. Remarkably, mucosal biopsies show only
minimal alterations.

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16
Q
A

FIGURE 17-27 Mechanisms of cholera toxin transport and signaling. After retrograde toxin
transport to the endoplasmic reticulum (ER), the A subunit is released by the action of
protein disulfide isomerase (PDI) and is then able to access the epithelial cell cytoplasm. In
concert with an ADP-ribosylation factor (ARF), the A subunit then ADP-ribosylates Gsα, which
locks it in the active, GTP-bound state. This leads to adenylate cyclase (AC) activation, and
the cAMP produced opens CFTR to drive chloride secretion and diarrhea

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17
Q

What are the clinical features of V.cholerae?

A

Most exposed individuals are asymptomatic or develop only mild diarrhea.

In those with severe disease there is an abrupt onset of watery diarrhea and vomiting following an incubation period of 1 to 5 days.

The voluminous stools resemble rice water and are sometimes described as having a fishy odor.

The rate of diarrhea may reach 1 liter per hour, leading to dehydration, hypotension, muscular cramping, anuria, shock, loss of consciousness, and death.

Most deaths occur within the first 24 hours after presentation.

Although the mortality for severe cholera is
about 50% without treatment, timely fluid replacement can save more than 99% of patients. Oral

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18
Q

What is the treatment for V.cholerae?

A

Oral rehydration is often sufficient. [59]

Because of an improved understanding of the host and
Vibrio proteins involved, new therapies are being developed including CFTR inhibitors that
block chloride secretion and prevent diarrhea. [60] Prophylactic vaccination is a long-term goal.

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19
Q

What is the most common bacterial enteric pathogen in developed countries and important cause of traveler’s diarrhea?

A

Campylobacter jejuni

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20
Q

Campylobacter jejuni is mostly associatd with ingestion of what?

A

Most infections are associated
with ingestion of improperly cooked chicken, but outbreaks can also be caused by unpasteurized milk or contaminated water.

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21
Q

What is the pathogenesis of Campylobacter infection?

A

remains poorly defined, but four major virulence
properties contribute:

  1. motility,
  2. adherence,
  3. toxin production, and
  4. invasion.
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22
Q

What is the function of Flagella in the pathogenesis of Campylobacter jejuni?

A

Flagella allow Campylobacter to be motile.

This facilitates adherance and colonization, which are necessary for mucosal invasion.

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23
Q

What causes the epithelial damage in the pathogenesis of C. jejuni?

A

Cytotoxins that cause epithelial damage and a cholera toxin–like enterotoxin are also released by some C. jejuni isolates.

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24
Q

What is the reason for the dysentery in Campylobacter jejuni?

A

Dysentery is generally associated with
invasion and only occurs with a small minority of Campylobacter strains.

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25
What explalins the enteric fever in Campylobacter jejuni?
Enteric fever occurs **when bacteria proliferate within the lamina propria and mesenteric lymph nodes.**
26
Campylobacter infection can result in what primarily in patients with HLA-B27?
reactive arthiritis
27
What are the other exra-intestinal complications of Campylobacter jejuni?
Other extra-intestinal complications, including : * erythema nodosum and * Guillain-Barré syndrome, * a flaccid paralysis caused by autoimmune-induced inflammation of peripheral nerves, are not HLA-linked. [62]
28
What is the pathogenesis of Guillain-Barré syndrome as a result of Campylobacter jejuni?
**Molecular mimicry** has been implicated in the pathogenesis of Guillain-Barré syndrome, as **serum antibodies to C. jejuni lipopolysaccharide cross-react with peripheral and central nervous system gangliosides.** Moreover, 15% to 50% of individuals with Guillain-Barré syndrome have **positive stool cultures or circulating antibodies to Campylobacter**. [63] Fortunately, Guillain-Barré syndrome develops in **0.1% or less of those infected with Campylobacter**
29
What is the description of Campylobacter?
* **comma-shaped,** * **flagellated,** * **Gram-negative organisms.**
30
Why is stool diagnosis preffered over biopsy in Campylobacter jejuni?
Diagnosis is primarily by **stool culture**, since **biopsy findings are *_nonspecific, and reveal acute self-limited colitis with features common to many forms of infectious colitis_***. [64]
31
What is the microscopic morphology of Campylobacter jejuni?
Mucosal and intraepithelial neutrophil infiltrates are prominent, particularly within the superficial mucosa ( Fig. 17-28A ); **cryptitis** (neutrophil infiltration of the crypts) and **crypt abscesses** (crypts with accumulations of luminal neutrophils) may also be present. Importantly, crypt architecture is preserved ( Fig. 17-28D ), although this can be difficult to assess in cases with severe mucosal damage.
32
FIGURE 17-28 Bacterial enterocolitis. * A, Campylobacter jejuni infection produces **acute, self-limited colitis.** Neutrophils can be seen within surface and crypt epithelium and a crypt abscess is present at the lower right. * B, In Yersinia infection the surface epithelium can be eroded by neutrophils and the lamina propria is densely infiltrated by sheets of plasma cells admixed with lymphocytes and neutrophils. * C, Enterohemorrhagic E. coli O157:H7 results in an ischemia-like morphology with surface atrophy and erosion. * D, Enteroinvasive * E. coli infection is a similar to other acute, self-limited colitides. Note the maintenance of * normal crypt architecture and spacing, despite abundant intraepithelial neutrophils.
33
What are the clinical features of Campylobacter jejuni?
Ingestion of as few as **500** C. jejuni organisms can cause disease **after an incubation period of up to 8 days.** **Watery diarrhea, either acute or following an influenza-like prodrome, is the primary symptom, and dysentery develops in 15% of patients.** Patients may shed bacteria for 1 month or more after clinical resolution. Antibiotic therapy is generally not required.
34
What is Shigella?
Shigella are **Gram-negative bacilli** that were initially isolated during the Japanese red diarrhea epidemic of 1897. Four major strains are now recognized. Shigella are **unencapsulated,** **nonmotile**, **facultative anaerobes** that belong to the **Enterobacteriaceae** and are **closely related to enteroinvasive E. coli**.
35
What is the only reservoir of Shigella spp?
Although **humans are the only known reservoir,** Shigella spp. remain **one of the most common causes of bloody diarrhea.** It is estimated that 165 million cases occur worldwide each year. [65] Given the infective dose of fewer than several hundred organisms and the presence of as many as 10 9 organisms in each gram of stool during acute disease,
36
What is the MOT of Shigella?
Shigella are **highly transmissible by the fecal-oral route** or **via contaminated water and food.**
37
Which are most commonly affected by Shigella?
In the United States and Europe, children in daycare centers, migrant workers, travelers to developing countries, and those in nursing homes are most commonly affected. [66,] [67] Most Shigella infections and deaths occur in children under 5 years of age, and in countries where Shigella is endemic it is responsible for approximately 10% of all pediatric diarrheal disease and as many as 75% of diarrheal deaths.
38
What is the pathogenesis of Shigella?
Shigella are **resistant to the harsh acidic environment of the stomach**, which **translates into an extremely low infective dose**. Once in the intestine, **organisms are taken up by M, or microfold,** epithelial cells, which are specialized for sampling and presentation of luminal antigens. Shigella **proliferate intracellularly, escape into the lamina propria, and are phagocytosed by macrophages,**in which they**induce apoptosis**. The **ensuing inflammatory process** **damages surface epithelia and allows Shigella**within the intestinal lumen to gain access to the colonocyte basolateral membrane, which is the only surface through which infection can occur in epithelial cells **(other than M cells**). All Shigella spp. carry **virulence plasmids**, some of which encode a **type III secretion system** capable of directly injecting bacterial proteins into the host cytoplasm. **S. dysenteriae serotype 1** also release the **Shiga toxin Stx,** which **inhibits eukaryotic protein synthesis resulting in host cell damage and death**
39
What toxin released by Shigella causes host cell damage and death?
**S. dysenteriae serotype 1** also release the Shiga toxin **Stx,** which inhibits eukaryotic protein synthesis resulting in host cell damage and death
40
Shigella infections are most prominent where?
Shigella infections are **most prominent in the left colon**, but the **ileum may also be involved**, perhaps **reflecting the abundance of M cells in the dome epithelium over the Peyer's patche**s.
41
What are the morphologic changes contributed by Shigella infection?
The **mucosa is hemorrhagic and ulcerated**, and **pseudomembranes may be present.** The histology of early cases is similar to other acute self-limited colitides, such as Campylobacter colitis, but because of the **tropism for M cells, aphthous-appearing ulcers similar to those seen in Crohn disease may occur**. The potential for confusion with chronic inflammatory bowel disease is significant, particularly if there is distortion of crypt architecture.
42
What is the clinical course of Shigella?
* **incubation period of as long as 4 days**, Shigella * causes **self-limited disease** * characterized by about **6 days of diarrhea, fever, and abdominal pain.** * The initially watery diarrhea progresses to a dysenteric phase in approximately 50% of patients, and constitutional symptoms can persist for as long as 1 month. * The subacute presentation that develops in a minority of adults is characterized by several weeks of waxing and waning diarrhea that can mimic new-onset ulcerative colitis. [68] * While duration is typically shorter in children, severity is often much greater. Confirmation of Shigella infection requires stool culture.
43
What is potential for confusion with inflammatory bowel disease in Shigella?
The potential for confusion with chronic inflammatory bowel disease is significant, particularly **if there is distortion of crypt architecture.**
44
What are the complications of
Complications of Shigella infection are uncommon and include : * Reiter syndrome, * a triad of sterile **arthritis, urethritis, and conjunctivitis** that preferentially affects HLA-B27-positive men between 20 and 40 years of age. * Hemolytic-uremic syndrome, which is typically **associated with enterohemorrhagic E. coli (EHEC),** may also occur after infection with S. dysenteriae **serotype 1 that secrete Shiga toxin** [69] [70] [71] ; **only Shigella organisms that secrete the toxin are associated with hemolytic-uremic syndrome** ( Chapter 20 ). *
45
What is Hemolytic-uremic syndrome?
which is **typically associated with enterohemorrhagic E. coli (EHEC)**, ***_may also occur after infection with S. dysenteriae serotype 1 that secrete Shiga toxin_*** [69] [70] [71] ; ***_only Shigella organisms that secrete the toxin are associated with hemolytic-uremic syndrom_***e ( Chapter 20 ).
46
What is the treatment for Shigella?
Antibiotic treatment shortens the clinical course and reduces the duration over which organisms are shed in the stool, but **antidiarrheal medications are contraindicated because they can prolong symptoms and delay Shigella clearance.**
47
Describe Salmonella.
Salmonella, which are classified within the **Enterobacteriaceae** family of **Gram-negative bacilli,** are divided into **Salmonella typhi**, the causative agent of **typhoid fever (**discussed in the next section) and **nontyphoid Salmonella**. Nontyphoid Salmonella infection is usually due to S. enteritidis; more than 1 million cases occur each year in the United States, and the prevalence is even greater in other countries. Infection is **most common in young children** and the **elderly, with peak incidence** in summer and fall.
48
What is the MOT of Salmonella?
Transmission is usually through **contaminated food,** particularly **raw or undercooked meat, poultry, eggs, and milk.**
49
What is the pathogenesis of Salmonella?
**Very few viable Salmonella** are **necessary to cause infection**, and the **absence of gastric acid, as in individuals with atrophic gastritis**or those on**acid-suppressive therapy, further reduces the required inoculum.** Salmonella possess virulence genes that encode a type III secretion system capable of transferring bacterial proteins into M cells and enterocytes. The transferred proteins activate host cell Rho GTPases, thereby triggering actin rearrangement and bacterial uptake that allow bacterial growth within phagosomes. In addition, **flagellin,** the core protein of bacterial flagellae, activates TLR5 on host cells and increases the local inflammatory response. [72] Similarly, bacterial lipopolysaccharide activates TLR4, although some Salmonella strains express a virulence factor that prevents TLR4 activation from occurring. Salmonella also secrete a molecule that induces epithelial release of the eicosanoid hepoxilin A3, thereby drawing neutrophils into the intestinal lumen and potentiating mucosal damage. [73] Mucosal TH17 immune responses limit infection to the colon.
50
?What is the morphology of Salmonella enteritis?
Morphology. The gross and microscopic features of Salmonella enteritis are non-specific and are similar to the acute self-limited colitis of Campylobacter and Shigella. **Stool cultures are essential for diagnosis**
51
What are the clinical features of Salmonella?
Salmonella infections are **clinically indistinguishable** from those **caused by other enteric pathogens,** and symptoms range from **loose stools to cholera-like** profuse diarrhea to dysentery. Fever often **resolves within 2 days,** but diarrhea can persist for a week and organisms can be shed in the stool for several weeks after resolution.
52
Why is antibiotic therapy not recommended in most case in Salmonella?
Antibiotic therapy is not recommended in most cases, **because it can prolong the carrier state** or **even cause relapse and does not typically shorten the duration of diarrhea**. [74] Most Salmonella infections are selflimited, but deaths do occur. The risk of severe illness and complications is increased in patients with malignancies, immunosuppression, alcoholism, cardiovascular dysfunction, sickle cell disease, and hemolytic anemia
53
What is the cause of typhoid fever?
Typhoid fever, also referred to as enteric fever , is caused by **Salmonella typhi and Salmonella** **paratyphi**. It affects up to 30 million individuals worldwide each year. The majority of cases in endemic countries are due to S. typhi, while infection by **S. paratyphi is more common among travelers, [**75] perhaps**because travelers tend to be vaccinated against S. typhi** (there are no effective S. paratyphi vaccines).
54
What the reason why S.paratyphi is more common among traveler's?
The majority of cases in endemic countries are due to S. typhi, while infection by **S. paratyphi is more common among travelers,**[75] perhaps**because travelers tend to be vaccinated against S. typhi (there are no effective S. paratyphi vaccines).**
55
Which is mostly affected by Typhoid fever?
In endemic areas children and adolescents are **affected most often,** but there is **no age preference in developed countries.** Infection is **strongly associated with travel to India, Mexico, the Philippines, Pakistan, El Salvador, and Haiti. [76]**
56
What is the sole reservoir for S. typhi and S.paratyphi?
Like Shigell**a, humans are the sole reservoir for S. typhi** and S. paratyphi and transmission occurs from **person to person or via food or contaminated water**. Gallbladder colonization with S. typhi or S. paratyphi may be associated with gallstones and the chronic carrier state
57
What is the pathogenesis of S.typhi?
S. typhi are **able to survive in gastric acid** and, once in the small intestine, are **taken up by and invade M cells.** Organisms are then engulfed by mononuclear cells in the underlying lymphoid tissue. Unlike S. enteritidis, S. typhi can then disseminate via lymphatic and blood vessels. This causes reactive hyperplasia of phagocytes and lymphoid tissues throughout the body
58
What is the morphology of TYPHOID FEVER?
Infection causes Peyer's patches in the terminal ileum to enlarge into **sharply delineated, plateau-like** elevations up to 8 cm in diameter. Draining mesenteric lymph nodes are also enlarged. Neutrophils accumulate within the superficial lamina propria, and macrophages containing bacteria, red blood cells, and nuclear debris mix with lymphocytes and plasma cells in the lamina propria. Mucosal shedding creates **oval ulcers, oriented along the axis of the ileum, that may perforate.** The draining lymph nodes also harbor organisms and are enlarged due to phagocyte accumulation. The spleen is enlarged and soft, with uniformly pale red pulp, obliterated follicular markings, and prominent phagocyte hyperplasia. The **liver shows small, randomly scattered foci** of parenchymal necrosis in which hepatocytes are replaced by macrophage aggregates, called **typhoid nodules**, that may also develop in the bone marrow and lymph nodes
59
What is the clinical feature of Typhoid fever?
Patients experience anorexia, abdominal pain, bloating, nausea, vomiting, and bloody diarrhea followed by a short asymptomatic phase that gives way to bacteremia and fever with flu-like symptoms. [77] Blood cultures are positive in more than 90% of affected individuals during the febrile phase, which may prompt antibiotic treatment and prevent further disease progression. [76] In patients who do not receive treatment the febrile phase is followed by up to 2 weeks of sustained high fevers and abdominal tenderness that may mimic appendicitis. Rose spots, small erythematous maculopapular lesions, are seen on the chest and abdomen. [77] Symptoms abate after several weeks in those who survive, although relapse can occur. [77] Systemic dissemination may cause extra-intestinal complications including encephalopathy, meningitis, seizures, endocarditis, myocarditis, pneumonia, and cholecystitis. Patients with sickle cell disease are particularly susceptible to ***_Salmonella osteomyelitis_***
60
What are the three Yersinia species are human pathogens?
* **Y. enterocolitica and** * **Y. pseudotuberculosis** * **Y. pestis**, the agent of pulmonic and bubonic plague.
61
GI Yersinia are more common in what geographical area?
GI Yersinia infections are more common in Europe than North America and are most frequently linked to ingestion of pork, raw milk, and contaminated water.
62
Which is more common between Y. enterocolitica and Y. pseudotuberculosis?
**Y. enterocolitica** is far more common than Y. pseudotuberculosis, and infections tend to cluster in the winter, possibly related to inadequately cooked foods served at holiday gatherings.
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What is the pathogenesis of Yersinia?
Yersinia **invade M cells** and **use bacterial adhesion** proteins, adhesins, to **bind to host cell β1 integrins.** A pathogenicity island encodes an **iron uptake system that mediates iron capture and transport;**similar iron transport systems**are also present in E. coli, Klebsiella, Salmonella**, and **enterobacteria**. In **Yersinia, iron enhances virulence and stimulates** **systemic dissemination,** explaining **why individuals with hemolytic anemia or hemochromatosis are more likely to develop sepsis and are at greater risk of death.**
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Why are Yersinia infected individuals with hemolytic anemia or hemochromatosis are more likely to develop sepsis and are at greater risk of death?
In **Yersinia, iron enhances virulence and stimulates systemic dissemination,** explaining why individuals with hemolytic anemia or hemochromatosis are more likely to develop sepsis and are at greater risk of death.
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Yersinia infections preferentially involve what area?
**ileum, appendix, and right colon** ( Fig. 17-28B ).
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Where do Yersinia organisms multiply?
The organisms multiply **extracellularly in lymphoid tissue,** resulting in *_**regional lymph node and Peyer's patch hyperplasia**_* and bowel wall thickening. [79] The mucosa overlying lymphoid tissue may become hemorrhagic, and aphthous-appearing ulcers may develop, along with neutrophil infiltrates (see Fig. 17-28B ) and **granulomas**, **increasing the potential for diagnostic confusion with Crohn disease.**
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Why do Yersinia infections have increasing potential for diagnostic confusion with Crohn disease?
The mucosa overlying **lymphoid tissue may become hemorrhagic**, and **aphthous-appearing ulcer**s may develop, along with **neutrophil infiltrates** (see Fig. 17-28B ) and ***_granulomas,_*** increasing the potential for diagnostic confusion with Crohn disease.
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What is the presentation of Yersina infection?
Clinical Features. People infected with Yersinia **generally present with abdominal pain, but fever and diarrhea may also occur.** **Nausea, vomiting, and abdominal tenderness are commo**n, and *_**Peyer's patch invasion with subsequent involvement of regional lymphatics can mimic acute appendicitis**_*in ***_teenagers and young adults_***. **Enteritis and colitis predominate in younger children.** Extraintestinal symptoms of **pharyngitis, arthralgia, and erythema nodosum** occur frequently.
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What are the diagnostic tool for Yersinia infection?
Yersinia can be detected **in stool cultures** on Yersinia-selective agar or, in cases with **extraintestinal disease, cultures of lymph nodes or blood**. [80]
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What are Postinfectious complications of Yersinia?
* **sterile arthritis,** * **Reiter syndrome,** * **myocarditis,** * **glomerulonephritis, and** * **thyroiditis**,
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What is the biology of Escherichia coli?
* Gram-negative bacilli that * colonize the healthy GI tract; * most are nonpathogeneic, but a subset cause human disease
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The subset of E.coli that cause human disease are classified according to what?
* morphology, * mechanism of pathogenesis, and in * vitro behavior.
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What are the subgroups of E.coli with major clinical relevance ?
* enterotoxigenic E. coli (ETEC), * enterohemorrhagic E. coli (EHEC), * enteroinvasive E. coli (EIEC), and * enteroaggregative E. coli (EAEC).
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What is ETEC?
Enterotoxigenic E. Coli. ETEC organisms are the ***_principal cause of traveler's diarrhea_*** and **spread via contaminated food or water**
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ETEC is common in what regions?
Infection is common in **underdeveloped regions**, and **children younger than 2 years of age**are particularly susceptible.
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What are the virulence factor of ETEC?
* heat-labile toxin (LT) and * heat-stable toxin (ST) * LT toxin
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What does the heat-labile toxin (LT) and heat-stable toxin (ST) do?
both induce chloride and water secretion while inhibiting intestinal fluid absorption.
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What is the function of LT toxin in E.coli?
The LT toxin is similar to cholera toxin and **activates adenylate cyclase,** **resulting in increased intracellular cAMP**. This **stimulates chloride secretio**n and, **simultaneously, inhibits absorption.** **ST toxins**, which have homology to the mammalian regulatory protein guanylin**, bind to guanylate cyclase and increase intracellular cGMP** with resulting effects on transport that are similar to those produced by LT.
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What is the histopathology induced by ETEC?
Like cholera, the histopathology induced by ETEC infection is limited.
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Clinical symptoms of ETEC include what?
* secretory, * noninflammatory diarrhea, d * ehydration, and, in severe cases, shock.
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EHEC are categorized as what?
**Enterohemorrhagic E. Coli.** * E. coli O157:H7 and * non-O157:H7 serotypes.
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Large outbreaks of E. coli O157:H7 in developed countries have been associated with what?
consumption of inadequately cooked ground beef, sometimes from fast-food establishments. Contaminated milk and vegetables are also vehicles for infection.
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Both O157:H7 and non-O157:H7 serotypes produce what kind of toxins?
**Shiga-like toxins**, and the morphology (see Fig. 17-28C ) and clinical symptoms are thus similar to S. dysenteriae.
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Which of the strains of EHEC more likely to cause large outbreaks?
**O157:H7 strains of EHEC** are more likely than non-O157:H7 serotypes to cause large outbreaks, **bloody diarrhea, and hemolytic-uremic syndrome.**
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Why EHEC have similar morphology and cinical symptoms with S.dysenteriae?
Both O157:H7 and non-O157:H7 serotypes ***_produce Shiga-like toxins_***, and the morphology (see Fig. 17-28C ) and clinical symptoms are thus similar to S. dysenteriae.
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What is EIEC?
Enteroinvasive E. Coli. EIEC organisms are **bacteriologically similar to Shigella** and are **transmitted via food, water, or by person-to-person contact.** While EIEC **do not produce toxins**, ***_they invade epithelial cells and cause nonspecific features of acute self-limited colitis_*** (see Fig. 17-28D ). EIEC infections are **most common among young children** in developing countries and are occasionally associated with outbreaks in developed countries
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What is EAEC?
Enteroaggregative E. Coli. EAEC organisms were identified on the **basis of their unique pattern of adherence to epithelial** **cells.** These organisms are now recognized as a **cause of diarrhea in children and adults in developed as well as developing countries.** These **can also be a cause of traveler's** **diarrhea.** [81]
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What is the pathogenesis of EAEC?
EAEC **attach to enterocytes via adherence fimbriae** and **are aided by dispersin**, a bacterial surface protein that **neutralizes the negative surface charge of lipopolysaccharide.** While the bacteria **do produce enterotoxins related to Shigella enterotoxin and ETEC ST toxin,** **histologic damage is minimal** and the **characteristic adherence lesions are only visible by electron microscopy.** [82] EAEC organisms **cause nonbloody diarrhea** that may be prolonged in individuals **with the acquired immunodeficiency syndrome (AIDS).**
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Pseudomembranous colitis is generally caused by what?
Clostridium difficile, is also known as antibioticassociated colitis or antibiotic-associated diarrhea. The latter terms **apply to diarrhea developing during or after a course of antibiotic therapy and may be due to C. difficile** as well as ***_Salmonella, C. perfringens type A, or Staphylococcus aureus._*** The latter two organisms produce enterotoxins and are common agents of food poisoning.
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What is the pathogenesis of PSEUDOMEMBRANOUS COLITIS?
It is likely that **disruption of the normal colonic flora by antibiotics *_allows C. difficile overgrowth._*** Although **almost any antibiotic may be responsible, *_third-generation cephalosporins are implicated most frequently._*** **Immunosuppression is also a predisposing factor for C. difficile colitis.** Toxins released by C. difficile *_**cause the ribosylation of small GTPases, such as Rho, and lead to disruption of the epithelial cytoskeleton, tight junction barrier loss, cytokine release, and apoptosis.**_*[83] The mechanisms by which these processes lead to the characteristic morphology of pseudomembranous colitis are incompletely understood.
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What is the morphology of fully developed C.difficile?
Fully developed C. difficile–associated colitis is **accompanied by formation of pseudomembranes**( Fig. 17-29A , B), made up of an**adherent layer of inflammatory cells and debris at sites of colonic mucosal injury**. While **pseudomembranes are not specific** and **may occur in ischemia and necrotizing infections**, the **histopathology of C. difficile–associated colitis is striking.** The surface epithelium is denuded, and the superficial lamina propria contains a dense infiltrate of neutrophils and occasional fibrin thrombi within capillaries. **Superficially damaged crypts** are di***_stended by a mucopurulent exudate that forms an eruption reminiscent of a volcano_*** ( Fig. 17-29C ). These exudates coalesce to form the pseudomembranes.
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FIGURE 17-29 Clostridium difficile colitis. * A, The colon is coated by tan pseudomembranes composed of neutrophils, dead epithelial cells, and inflammatory debris (endoscopic view). * B, Pseudomembranes are easily appreciated on gross examination. * C, Typical pattern of neutrophils emanating from a crypt is reminiscent of a volcanic eruption.
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What are the risk factors of C.difficile?
Risk factors for C. difficile–associated colitis include: * advanced age, * hospitalization, and * antibiotic treatment. The organism is particularly prevalent in hospitals; as many as 30% of hospitalized adults are colonized with C. difficile (a rate tenfold greater than the general population), but most colonized patients are free of disease.
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What are the clinical presentation of individuals with C.difficile?
Individuals with C. difficile–associated **colitis present with fever**, **leukocytosis, abdominal pain, cramps, hypoalbuminemia, watery diarrhea, and dehydration.** Fecal leukocytes and occult blood may be present, but grossly bloody diarrhea is rare.
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What is the diagnosis of C.difficile?
Diagnosis of C. difficile–associated colitis is usually accomplished by **detection of C. difficile toxin**, rather than culture, and is supported by the characteristic histopathology. **Metronidazole or vancomycin** are generally effective therapies, but antibiotic-resistant and hypervirulent C. difficile strains as well as recurrent disease are increasingly common.
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What is Whipple disease?
Whipple disease is a rare, multivisceral chronic disease first described as intestinal lipodystrophy in 1907 by George Hoyt Whipple. A mere 27 years later the pathologist went on to win the Nobel Prize for his work on pernicious anemia. He was a contemporary, but not a relative, of Allen Oldfather Whipple, the surgeon who pioneered the pancreatoduodenectomy.
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What is the description of the Whipple's case?
Whipple's original case report described an individual with **malabsorption, lymphadenopathy, and arthritis of undefined origin.**
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What was demonstrated in postmortem examination of Whipple disease
Postmortem examination demonstrated the **presence of foamy macrophages and large numbers of argyrophilic rods in the lymph nodes, providing evidence that the disease was infectious**. [85]
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What are the etiologic agen responsible for Whipple disease?
The **Gram-positive actinomycete**, named *_**Tropheryma whippelii,**_* that is responsible for Whipple disease was identified by PCR in 1992 and finally cultured in 2000. [86]
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What pathogenesis of Whipple disease?
Clinical symptoms occur because **organism-laden macrophages accumulate within the small intestinal lamina propria** and **mesenteric lymph nodes,** causing **lymphatic obstruction.** Thus, the **malabsorptive diarrhea of Whipple disease is due to impaired lymphatic transport.**
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What is the morpholofic hallmark of Whipple disease?
The morphologic hallmark of Whipple disease is a *_**dense accumulation of distended,****foamy macrophages in the small intestinal lamina propria**_* ( Fig. 17-30A ). The macrophages contain **periodic acid–Schiff (PAS) positive**, diastase-resistant granules that represent lysosomes stuffed with partially digested bacteria ( Fig. 17-30B ).
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What is the appearance of Whipple disease in electron microscope?
Intact rodshaped bacilli can also be identified by electron microscopy ( Fig. 17-30C ). A similar infiltrate of foamy macrophages is present in intestinal tuberculosis ( Fig. 17-30D ), and in both diseases the organisms are PAS-positive. However, the acid-fast stain can be used to distinguish between these, since mycobacteria stain positively ( Fig. 17-30E ) **while T. whippelii do not.**
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What is the appearance of the villous in Whipple disease?
The villous expansion caused by the dense macrophage infiltrate **imparts a shaggy gross appearance to the mucosal surface**. Lymphatic dilatation and mucosal lipid deposition account for the common endoscopic detection of white to yellow mucosal plaques. In Whipple disease, **bacteria-laden macrophages can accumulate within mesenteric lymph** nodes, synovial membranes of affected joints, cardiac valves, the brain, and other sites.
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FIGURE 17-30 Whipple disease and mycobacterial infection. * A, H&E staining shows effacement of normal lamina propria by a sheet of swollen macrophages. * B, PAS stain highlights macrophage lysosomes full of bacilli. Note the positive staining of mucous vacuoles in the overlying goblet cells. * C, An electron micrograph of one lamina propria macrophage shows these bacilli within the cell (top) and at higher magnification (inset). * D, The morphology of mycobacterial infection can be similar to Whipple disease, particularly in the immunocompromised host. Compare with A. E, Mycobacteria are positive with stains for acid-fast bacteria.
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What is the clinical presentation of Whipple disease?
The clinical presentation of Whipple disease is usually a **triad of diarrhea, weight loss, and malabsorption**. Extraintestinal symptoms, which can exist for months or years before malabsorption, include arthritis, arthralgia, fever, lymphadenopathy, and neurologic, cardiac, or pulmonary disease.
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VIRAL GASTROENTERITIS Symptomatic human infection is caused by several distinct groups of viruses. The most common are discussed here.
* Norovirus * Rotavirus. * Adenovirus.
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What is Norovirus.?
This was previously known as norwalk-like virus and is **a common cause of nonbacterial infectious gastroenteritis**. [87] These are **small icosahedral viruses** with a **single-stranded RNA** genome that forms a genus within the Caliciviridae family. Norovirus causes approximately half of all gastroenteritis outbreaks worldwide and is a **common cause of sporadic gastroenteritis in developed countries.** Local outbreaks are usually related to contaminated food or water, but **person-to-person transmission** underlies **most sporadic cases**. Infections spread easily within schools, hospitals, nursing homes, and, most recently, cruise ships.
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What is the clinical course of Norovirus?
Following a **short incubation period,**affected individuals develop**nausea, vomiting, watery diarrhea, and abdominal pain**. Biopsy morphology is nonspecific. When detected, abnormalities are most evident in the **small intestine and include mild villous shortening, epithelial vacuolization, loss of the microvillus brush border, crypt hypertrophy, and lamina propria infiltration by lymphocytes**( Fig. 17-31A ). The **disease is self-limited**.
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FIGURE 17-31 Infectious enteritis. * A, Histologic features of viral enteritis include increased numbers of intraepithelial and lamina propria lymphocytes and crypt hypertrophy. * B, Diffuse eosinophilic infiltrates in parasitic infection. This case was caused by Ascaris (upper inset) , but a similar tissue reaction could be caused by Strongyloides (lower inset) . * C, Schistosomiasis can induce an inflammatory reaction to eggs trapped within the lamina propria. * D, Entamoeba histolytica in a colon biopsy specimen. Note some organisms ingesting red blood cells. * E, Giardia lamblia, which are present in the luminal space over nearly normal-appearing villi, are easily overlooked. * F, Cryptosporidia organisms are seen as small blue spheres that appear to lay on top of the brush border but are actually enveloped by a thin layer of host cell cytoplasm
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What is Rotavirus?
This **encapsulated** virus with a **segmented double-stranded RNA** genome infects 140 million people and causes **1 million deaths each year**, making ***_rotavirus the most common cause of severe childhood diarrhea and diarrheal mortality worldwide_***. Children between **6 and 24 months of age are most vulnerable**.
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Why are children between 6 and 24 months of age are most vulnerable for Rotavirus?
Protection in the **first 6 months of life is** probably **due to the presence of antibodies to rotavirus in breast milk,** while **protection beyond 2 years is due to immunity that develops following the first infectio**n. [88] Outbreaks in hospitals and daycare centers are common, and infection spreads easily; the estimated minimal infective inoculum is only 10 viral particles.
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What is the pathogenesis of Rotavirus?
Rotavirus **selectively infects and destroys mature enterocytes** in the small intestine, and the **villus surface is repopulated by immature secretory cells.** This results in loss of absorptive function and net secretion of water and electrolytes that is compounded by an osmotic diarrhea from incompletely absorbed nutrients. Like norovirus, rotavirus has a **short incubation period followed by several days of vomiting and watery diarrhea.** Vaccines are now available, and their use will probably change the epidemiology of rotavirus infection.
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What is Adenovirus?
Adenovirus. The **second most common cause of pediatric diarrhea** (after rotavirus), adenovirus also **affects immunocompromised patients**. [89] Small intestinal biopsy specimens can show epithelial degeneration but more often exhibit nonspecific villous atrophy and compensatory crypt hyperplasia. Viral nuclear inclusions are uncommon. Disease typically presents **after an incubation period of 1 week with nonspecific symptoms that include diarrhea, vomiting, and abdominal pain.** Fever and weight loss may also be present. Symptoms generally resolve within 10 days.
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