Chapter17: INTESTINES:Infectious Enterocolitis Flashcards
Enterocolitis can present with a broad range of symptoms including what?
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.
TABLE 17-7 – Features of Bacterial Enterocolitides
Infection Type
- Cholera
- Campylobacter spp.
- Shigellosis
- Salmonellosis
- Enteric (typhoid) fever
- Yersinia spp.
- Escherichia coli
- Enterotoxigenic
(ETEC) - Enterohemorrhagic
(EHEC) - Enteroinvasive (EIEC)
- Enteroaggregative
(EAEC)
- Enterotoxigenic
- Pseudomembranous
colitis (C. difficile - Whipple disease
- Mycobacterial infection
TABLE 17-7 – Features of Bacterial Enterocolitides
Geograph
- 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
- Enterotoxigenic (ETEC)
- Pseudomembranous colitis (C. difficile: colitis (C. difficile): Developing countries
- Whipple disease: Rural > urban
- Mycobacterial infection: Worldwide
TABLE 17-7 – Features of Bacterial Enterocolitides
Reservoir
- 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
-
Enterotoxigenic (ETEC)
-
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
TABLE 17-7 – Features of Bacterial Enterocolitides
Transmission
- 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
-
Enterotoxigenic (ETEC)
-
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
TABLE 17-7 – Features of Bacterial Enterocolitides
Epidemiology
- 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
-
Enterotoxigenic (ETEC)
- Pseudomembranous colitis (C. difficile: colitis (C. difficile):Immunosuppressed, antibiotic-treated
- Whipple disease: Rare
- Mycobacterial infection:Immunosuppressed
TABLE 17-7 – Features of Bacterial Enterocolitides
Affected GI Sites
- 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
-
Enterotoxigenic (ETEC)
- Pseudomembranous colitis (C. difficile: colitis (C. difficile):Colon
- Whipple disease: Small intestine
- Mycobacterial infection:Small intestine
TABLE 17-7 – Features of Bacterial Enterocolitides
Symptoms
- 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
- Bloody
-
Enteroinvasive (EIEC)
- Bloody diarrhea
-
Enteroaggregative (EAEC)
- Nonbloody diarrhea,afebril
-
Enterotoxigenic (ETEC)
- Pseudomembranous colitis (C. difficile: colitis (C. difficile):Watery diarrhea, fever
- Whipple disease: Malabsorption
- Mycobacterial infection:Malabsorption
TABLE 17-7 – Features of Bacterial Enterocolitides
Complications
- 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
Describe the Vibrio cholerae.
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.
What is the MOT of V. cholerae?
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.
Why is there a marked seasonal variation of Vibrio cholerae?
There is a marked seasonal variation in most climates due to rapid growth of Vibrio bacteria at warm temperatures
What is the only reservoir of V. cholerae?
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
What is the pathogenesis of V.cholerae?
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.
What is the mechanism that induces diarrhea in Cholerae toxin?
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.
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
What are the clinical features of V.cholerae?
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
What is the treatment for V.cholerae?
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.
What is the most common bacterial enteric pathogen in developed countries and important cause of traveler’s diarrhea?
Campylobacter jejuni
Campylobacter jejuni is mostly associatd with ingestion of what?
Most infections are associated
with ingestion of improperly cooked chicken, but outbreaks can also be caused by unpasteurized milk or contaminated water.
What is the pathogenesis of Campylobacter infection?
remains poorly defined, but four major virulence
properties contribute:
- motility,
- adherence,
- toxin production, and
- invasion.
What is the function of Flagella in the pathogenesis of Campylobacter jejuni?
Flagella allow Campylobacter to be motile.
This facilitates adherance and colonization, which are necessary for mucosal invasion.
What causes the epithelial damage in the pathogenesis of C. jejuni?
Cytotoxins that cause epithelial damage and a cholera toxin–like enterotoxin are also released by some C. jejuni isolates.
What is the reason for the dysentery in Campylobacter jejuni?
Dysentery is generally associated with
invasion and only occurs with a small minority of Campylobacter strains.
What explalins the enteric fever in Campylobacter jejuni?
Enteric fever occurs
when bacteria proliferate within the lamina propria and mesenteric lymph nodes.
Campylobacter infection can result in what primarily in patients with HLA-B27?
reactive arthiritis
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]
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
What is the description of Campylobacter?
- comma-shaped,
- flagellated,
- Gram-negative organisms.
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]
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.
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.
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.
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.
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,
What is the MOT of Shigella?
Shigella are highly transmissible by the fecal-oral route or via contaminated water and food.
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.
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 theyinduce apoptosis.
The ensuing inflammatory process damages
surface epithelia and allows Shigellawithin 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
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
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 patches.
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.
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.
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.
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 ).
*
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 syndrome ( Chapter 20 ).
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.
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.
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
