Chapter 17: Infectious Enterocolitis Flashcards
What is the morphology of Vibrio cholerae?
Comma-shaped; gram (-) bacteria
What is the reservoir and mode of transmission for Vibrio cholerae?
Reservoir = shellfish
MOT = fecal-oral; water
Is Vibrio cholerae invasive and which components of the organism are related to its virulence?
- Non-invasive
- Cholera toxin
- Flagella for motility and attachment
- Hemagglutinin for detachment and shedding in stool
In severe cases of Cholera what are the signs and symptoms?
What are the characteristics of the diarrhea?
When is the onset?
- Abrupt onset of vomiting and watery diarrhea after 1-5 day period
- Voluminous stools resembling rice water and said to have fish odor
What is the rate of diarrhea in severe cases of cholera and what problems can this create?
When do most deaths occur?
Treatment?
- Up to 1L/hr
- Dehydration, hypotension, cramping, anuria, shock, and LOC
- Death usually within first 24 hours
- Timely fluid replacement can save more than 99% of pts
What is the morphology and mode of transmission for Campylobacter spp.?
- Comma-shaped; flagellated; gram (-) bacteria
- Poulty (undercooked), milk (unpasteurized), other foods
What is the most common bacterial enteric pathogen in developed countries and important cause of traveler’s diarrhea?
Campylobacter jejuni
What are the 4 major properties contributing to the virulence of Campylobacter jejuni?
- Motility - flagella
- Adherence
- Toxin production - cytotoxin + cholera toxin-like enterotoxin
- Invasion
What are some of the signs and symptoms of Campylobacter infection?
How can sx’s of a fever be produced?
- Watery diarrhea, either acute or following an influenza-like prodrome
- Dysentery (blood stool) in minority of patients
- Enteric fever if bacteria prolif. in lamina propria and mesenteric LNs
What is the association of Campylobacter infection and HLA-B27?
Can result in reactive arthritis
What are 2 possible complications of Campylobacter infection that are not HLA linked?
- Erythema nodosum
- Guillain-Barre syndrome
*NOT HLA linked, like reactive arthritis
How is the diagnosis of Campylobacter infection made?
Which immune cell infiltrates predominate and where are they found?
- Primarily by stool culture
- Intraepithelial neutrophilinfiltrates withinsuperficial mucosaandcrypts (cryptitis)
What is the affect of Campylobacter infection on crypt architecture?
- May see neutrophil infiltration of crypts (cryptitis) or crypt abscesses
- Architecture of cyrpts are PRESERVED (important)
What is the morphology of Shigella?
Mode of transmission?
Reservoir?
- Gram (-); Unencapsulated; Non-motile;Facultative anaerobes
- MOT = fecal-oral, food, water
- Reservoir = humans
Shigella is one of the most common causes of?
Dysentery (blood diarrhea)
Where are the most common sites for infection by Shigella and who is most at risk?
Most deaths occur in whom?
- In US and Europe, daycares, migrant workers, travelers, and those in nursing homes
- Most deaths occurs in children <5 yo
Why is such a low infective dose of Shigella required to cause symptoms?
- Acid-STABLE
- Able to resist the harsh acidic enviornment of the stomach
Once Shigella are in the intestine how are they taken up and what do they do?
- Taken up by Microfold (M cells)
- Proliferate intracellularly, escape into LP to be phagocytosed by MØ’s in which they induce apoptosis
- Inflammatory response damages surface epithelia and allows Shigella access to basolateral membrane for invasion
All Shigella spp. carry which virulence plasmids allowing for direct injeciton of bacterial proteins into host cytoplasm?
Type III secretion system
Shigella dysenteriae serotype 1 are able to release which special toxin and what does this cause?
- Shiga toxin Stx
- Inhibits eukaryotic protein synthesis –> host cell damage + death
Shigella most prominently infect which part of the GI, likely due to what?
What is the morphology of the mucosa?
- Left colon and Ileum –> M cells prominent in Peyers patches here
- Mucosa = ulcerated + hemorrhagic w/ pseudomembranes
What is the most common clinical presentation of a pt w/ Shigella infection?
- 1 week of diarrhea w/ fever and abdominal pain
- Initially watery diarrhea may progress to dysenteric phase w/ sx’s lasting up to a month
Complications of Shigella infection are related to which immune system component and presents as a triad of sx’s most commonly in which patient population?
- HLA-B27 in men ages 20-40 yo
1) Sterile reactive arthritis
2) Urethritis
3) Conjunctivitis
The Shigella dysenteriae serotype 1 that secretes shiga toxin is somtimes associated w/ what clinical complication?
Hemolytic-uremic syndrome (typically assoc. w/ EHEC)
Which treatment is indicated and which is contraindicated in patients w/ Shigella infection?
- Antibiotics may shorten clinical course
- Antidiarrheals = CONTRAINDICATED –> prolong sx’s and delay clearance
Salmonellosis is usually due to which type of Salmonella**?
Salmonella enteritidis
Salmonella infection is most commonly transmitted how?
Which age groups most affected?
Which time of year do infections peak?
- Meat, poultry, and eggs/milk
- Young children and Older adults
- Peak incidence in fall and summer
What are predispositions for the development of Salmonella infection?
- Atrophic gastritis or on acid-suppressive therapy (PPIs)
- Genetic defects in TH17 –> Disseminated salmonellosis
Which virulence factor allows for Salmonella invade and infect humans?
Explain the pathogenesis of invasion.
- Type III secretion system transfers bacterial proteins –> M cells and enterocytes
- Proteins activate host Rho GTPases –> actin rearrangement and bacterial endocytosis for growth in endosomes
What do the flagellin and LPS of Salmonella activate inside humans are what does this result in?
- Flagellin –> TLR5 –> Increased inflammtory response
- LPS –> TLR4
How do Salmonella indirectly cause increased neutrophils and potentiate mucosal damage?
Secrete molecule inducing epithelial cells to release eicosanoid hepoxilin A3
Which immune cells limit infection by Salmonella?
TH1 and TH17
What is essential for the diagnosis of Salmonella infection?
Stool culture (+)
Typhoid fever (enteric fever) is caused by which organism and its 2 subtypes?
Which subtype is associated with endemic countries and which with travelers?
- Salmonella enterica
- Subtypes:
- Typhi* (endemic countries)
- Paratyphi* (travelers)
What is the reservoir for Salmonella enterica?
Mode of transmission?
- Humans = reservoir
- MOT = fecal-oral and water
Typhoid fever (Salmonella enterica) is strongly associated with travel to which countries?
India, Mexico, Philippines, Pakistan, El Salvador, and Haiti
Gallbladder colonization by S. typhi or S. paratyphi is associated with?
- Gallstones
- Chronic carrier state
Explain the pathogeneis of S. typhi infection (i.e., how do they invade?)
- Survive in gastric acid–> small intestine –> taken up byM cells
- Bacteria engulfed by mononuclear cells in lymph tissue
- Can disseminate via lymph and blood causing reactive hyperplasia of phagocytes and lymph tissue throughout body
What is seen morphologically in the Peyer patches, Mesenteric LN’s, Spleen, and Liver of a person with S. typhi infection (typhoid fever)?
Where in the GI are the Peyer Patches affected?
- Peyer patches of terminal ileum –> enlarge, sharply delineated, plateau-like elevations
- Mesenteric LNs –> enlarged
- Spleen –> enlarged w/ uniform pale red pulp; prom. phagocyte hyperplasia
- Liver –> small, scattered foci of parenchymal necrosis in which hepatocytes are replaced by MØ aggregates –> typhoid nodules
What are the phases of Typhoid Fever and symptoms involved in each?
- Pts have anorexia, abd. pain, bloating, nausea, vomiting, and blood diarrhea
- Followed by short asymptomatic phase
- Gives way to bacteremia and fever w/ flu-like sx’s
Are antibiotics recommended for Typhoid Fever?
Yes, can prevent further disease progression
In patients with Typhoid Fever, not treated w/ antibiotics what additional signs and symptoms may develop?
- Sustained high fevers
- Abdominal tenderness which may mimic appendicits
- Rose spots = erythematous maculopapular lesions on chest and abd.
Systemic dissemination of S. typhi may lead to what complications?
- Encephalopathy
- Meningitis
- Seizures
- Endocarditis
- Myocarditis
- Pneumonia
- Cholecystitis
Which patient population is particularly susceptible to developing Salmonella osteomyelitis?
Sickle cell disease pts
Which 2 types of Yersiniai cause GI disease?
Which is more common?
1) Yersinia enterocolitica = more common
2) Yersinia pseudotuberculosis
Where are Yersinia infections most common?
Mode of transmission?
Time of year infections are most common?
- Europe
- Pork, milk, water
- More common in winter
Which cells does Yersinia invade and which virulence factors does it contain allowing for its pathogenicity?
Which system allows for enhanced virulence and systemic dissemination?
- Invades M cells and uses adhesins to bind host β1 integrins
- Iron uptake system to capture and mediate transport of iron; which enhances its virulence and stimulates systemic dissemination
Which predisposition by some patients increases the chance of developing sepsis and death when infected by Yersinia?
- Pts w/ increased non-heme iron
- Such as certain chronic anemias or hemochromatosis
Yersinia infections preferentially involve which parts of the GI?
Ileum, appendix, and right colon
What are some of the characteristic morpho, histo, and gross changes associated with Yersinia infection?
Predominant immune infiltrate?
- Regional LN and Peyer patch hyperplasia
- Bowel wall thickening
- Mucosa overlying lymph tissue –> hemorrhagic, apthous-like erosions, and ulcers
- Neutrophils and granulomas
Peyer patch invasion with subsequent involement of regional lymphatics by Yersinia can cause symptoms which are confused with what other pathology in teens and young adults?
Acute appendicits
What are common extraintestinal symptoms of Yersinia infection?
- Pharyngitis
- Arthralgia
- Erythema nodosum
What are some of the postinfectious complications associated withYersinia?
- Reactive arthritis, Urethritis, Conjunctivitis (like Shigella)
- Myocarditis
- Erythema nodosum (like Campylobacter)
- Kidney disease
Which subgroup of E. coli is the principal cause of traveler’s diarrhea and spreads via contaminated water/food?
Enterotoxigenic E. Coli (ETEC)
Which age group is particularly susceptible to infection by ETEC?
Children <2 yo in developing countries
What are the 2 main toxins of ETEC and what is the MOA of each?
Net effect of these toxins?
- Heat-labile toxin (LT) –> similar to cholera toxin (activates AC = incrased cAMP) –> Cl- secretion
- Heat-stabile toxin (ST) –> homology to guanylin = binds to GC = increased cGMP –> similar effects of LT
- Toxins cause Cl- + H2O secretion and inhibit fluid absorption
What is the clinical manifestations (signs/symptoms) of ETEC infection?
- Secretory, noninflammatory diarrhea –> dehydration
- Severe cases = shock
Which subtype of E. coli is an important cause of endemic diarrhea as well as diarrheal outbreaks in children <2 yo?
Enteropathogenic E. Coli (EPEC)
EPEC are characterized by their ability to produce what type of lesion?
Describe this lesion
- (A/E) lesions = attaching and effacing
- Attach tightly to enterocyte apical membranes
- Cause local loss –> effacement of the microvilli
The proteins necessary for creating the A/E lesions seen w/ EPEC infections are encoded by which pathogenicity island?
What are the proteins encoded?
- Locus of enterocyte effacement (LEE)
- Encodes: Tir –> inserted into intestinal epithelial cell PM and acts as receptor for bacterial outer membrane protein, intimin
- Encodes: type III secretion system (similar to Shigella)
Which bacterial protein encoded by the espE gene is used for molecular detection and diagnosis of EPEC infection?
Intimin
How is Enterohemorrhagic E. Coli (EHEC) categorized?
- O157:H7
- non-O157:H7
What is the reservoir for EHEC and is transmitted how?
- Cows = reservoir
- Transmitted via consumption of undercooked beef, also milk and vegetables
What is produced by O157:H7 and non-O157:H7 serotypes of EHEC that contributes to its pathogenecity?
Symptoms are similar to infection by what organism?
Which serotype is more likely to produce large outbreaks?
- Shiga-like toxin –> Sx’s similar to S. dysenteriae infection
- O157:H7 more likely to cause large outbreaks
What are the symptoms and complications of EHEC infection, especially by the O157:H7 serotype?
- Bloody diarrhea
- Hemolytic uremic syndrome (HUS)
- Ischemic colitis
Are antibiotics recommended for treatment of EHEC; why or why not?
- No!
- Cause increased release of Shiga toxin –> enhancing risk for HUS, especially in children
Which E. Coli subtype is bacteriologically similar to Shigella and is transmitted via food, water, or by person-to-person contact?
Enteroinvasive E. Coli (EIEC)
What toxins are produced by EIEC and what is the clinical course of infection?
- Do not produce toxins
- Invade epithelial cells and cause non-specific features of acute self-limited colitis
Enteroaggregative E. Coli (EAEC) were identified on the basis of their unique what?
Unique pattern of adherence to epithelial cells
How does EAEC uniquely attach to enterocytes, which virulence factors are used?
- Via adherence fimbriae and are aided by dispersin
- Dispersin is a surface protein which neutralizes the negative surface charge of LPS
Which toxins are produced by EAEC organisms?
- Enterotoxin related to Shigella enterotoxin
- ETEC ST toxin (heat-stable toxin)
What are the clinical manifestations of EAEC infection and which popluation most often affected?
- Non-bloody diarrhea (traveler’s)
- Children/adults in both developing + developed countries
- Diarrhea may be prolonged in immunodeficient pt
Which organism is responsible for Pseudomembranous Colitis?
C. difficile
Which factor most likely contributes to bacterial overgrowth by C. difficile?
Toxins released by this organism cause what?
- Disruption of normal colonic microbiota by antibiotics; immunodeficiency = pre-disposing factor
- Toxins cause ribosylation of small GTPases (i.e., Rho) –> disruption of the epithelial cytoskeleton, tight junction barrier loss, cytokine release, and apoptosis
Crypts w/ mucopurulent exudate of neutrophils that forms eruption reminiscent of a volcano is characteristic of what infection?
C. difficile —> pseudomembranous colitis
Diagnosis of C. difficile-associated colitis is usually accomplished how?
Detection of C. difficile toxin in stool and supported by histopathology
What is a major challenge in C. difficile-associated colitis and a complication which may arise?
- Recurrent infection is common
- Toxic megacolon may occur
Which rare disease, was first described as intestinal lipodystrophy?
Whipple Disease
How does lymphatic obstruction occur in Whipple Disease?
Leads to what?
- Organism-laden MØ’s accumulate within SI lamina propria and Mesenteric LN’s
- Malabsorptive diarrhea
Postmortem examination of someone with Whipple Disease will show what histological characteristics?
Gross characteristics?
- Foamy macrophages in lamina propria and large #s of agyrophilic rods in LN’s
- Villous expansion caused by dense MØ infiltrate imparting shaggy gross appearance to mucosal surface
Which stain is used the visualize macrophages in Whipple Disease?
How can it be differentiated from the similar looking intestinal tuberculosis?
- PAS
- Used acid-fast to differentiate because T. whippelii will not stain, while mycobacteria will stain (+)
In Whipple disease, bacteria-laden macrophages can accumulate where?
- Mesenteric LNs (malabsorption)
- Synovial membranes (arthritis)
- Cardiac valves
- Brain (CNS disease)
Whipple disease most commonly affects who?
Caucasian men, particularly farmers and those w/ occupational exposure to soil or animals
What is the clinial triad of sx’s associated w/ Whipple disease?
1) Diarrhea
2) Weight loss
3) Arthralgia
Which extraintestinal symptoms of Whipple disease may persist for months or years before malabsorption?
- Arthritis
- Arthralgia
- Fever
- LAD
- Neuro, Cardiac, or Pulmonary disease
Which icosahedral virus w/ a SS-RNA genome is a common cause of gastroenteritis worldwide and severe diarrhea in infants?
Norovirus (Caliciviridae family)
Local norovirus outbreaks are usually related to what?
Which form of transmission underlies most sporadic cases?
- Contaminated food or water
- Person-to-person transmission underlies most sporadic cases
Where is infectious spread of Norovirus commonly seen?
- Schools, hospitals, and nursing homes
- Common on cruise ships
Norovirus infection is a significant problem in which patient population?
Leads to what problems?
- Immunocompromised (i.e., transplants, tx for GVHD, or HSC transplants)
- Can have 9 months of persistent diarrhea –> malnutrition and dehydr.
- Increased morbidity of underlying conditions
What type of Virus is Rotavirus?
Encapsulated w/ segmented DS-RNA gnoma
Which patient population is most vulnerable to infection by Rotavirus?
Children between ages 6 -24 months
What type of vaccine exists for Rotavirus?
Who is it contraindicated in?
Has been associated w/ what adverse effect?
- Live-attenuated
- Containdicated in pts w/ immunodeficiency
- Vaccine has been associated with intussusception
Rotavirus selectively infects and destroys what?
Mediated by which viral factor?
- Mature enterocytes of the small intestine, villus surface is repopulated by immature secretory cells
- Mediated by NSP4, which can induce epithelial apoptosis
The epithelial damage caused by Rotavirus leads to a loss of which function?
Contributes to the symptoms of infection how?
- Loss of absorptive function
- Net secretion of H2O + electrolytes w/ osmotic diarrhea which is 2’ to malabsorption
Adenovirus is a common cause of which GI dysfunction and in which population?
Pediatric diarrhea
Small intestinal biopsies of Adenovirus infection show which intestinal changes?
Non-specific villous atrophy + compensatory crypt hyperplasia
What are 2 common nematodes (round worms) which cause parasitic enterocolitis?
1) Ascaris lumbricoids
2) Strongyloides
Upon Ascaris lumbricoides return to the small intestine to mature into adult worm, what reaction may induced?
May manifest clinically how?
- Eosinophilic reaction
- Physical obstruction of intestine or biliary tree
- Larvae can also form hepatic abscesses and causes Ascaris pneumonitis
How does Strongyloides cause infection?
Penetrates unbroken skin –> migrate thru lungs –> reside in small intestine where they mature
What is unique of Strongyloides life-cycle and because of this infection in which population may pose a serious problem?
- Do NOT require ova or larval stage outside human and the eggs can hatch within intestine
- Release larvae that penetrate mucosa and cause an autoinfection, hence, infection can persist for life
- Immunosuppressed can develop overwhelming autoinfection
Stronglyloides infection incites a strong ________ reaction and induces _________ eosinophilia
Stronglyloides infection incites a strong tissue reaction and induces peripheral eosinophilia
Necator duodenale and Ancylostoma duodenale are what type of parasite?
Hookworms
Necator duodenale and Ancylostoma duodenale get into the GI tract how?
Do what in the duodenum?
- Larva penetrate skin –> systemic cir. –> lungs –> coughed –> swallowed
- In duodenum worms attach to mucosa, suck blood, and reproduce
What do Necator duodenale and Ancylostoma duodenale in the duodenum cause?
Chronic infection can lead to what deficiency?
Diagnosed how?
- Multiple superficial erosions + Focal hemorrhage + Inflammatory infiltrates
- Iron deficiency anemia (chronic infection)
- Diagnosed via eggs in fecal smears
Enterobius vermicularis is what type of parasite?
Pinworm
How do the symptoms produced by Enterobius vermicularis lead to infection?
- Adult worms in intestine migrate to anus at night, deposit eggs on perirectal mucosa
- Eggs cause intense irritation/itching –> contamination of fingers –> human-to-human transmission via fecal-oral route
Diagnosis of Enterobius Vermicularis?
Scotch tape test
Schistosomiasis is a disease of the intestines most commonly taking what form?
Symptoms are caused by?
What are 2 possible symptoms?
- Most commonlytakes form ofadult wormsresiding inmesenteric vs.
- Sx’s: trapping of eggs in mucosa and submucosa –> granulomatous immune rxn –> bleeding and even obstruction
What are the 3 primary species of intestinal cestodes that infect humans?
Which tapeworm does each represent?
1) Diphyllobothrium latum –> fish tapeworm
2) Taenia solium –> pork tapeworm
3) Hymenolepis nana –> dwarf tapeworm
Which intestinal cestode can occasionally cause B12 deficiency and megaloblastic anemia due to it competing for host dietary B12?
Diphyllobothrium latum = fish tapeworm
What is the route of transmission for Entamoba histolytica and is most often seen in what countries?
- Fecal-oral
- Mexico, India, and Columbia
Once the cysts of E. histolytica are ingested what occurs in the body?
Chitin wall allows resistance to gastric acid –> colonize epi. surface of the colon and release trophozoites
Which parts of colon most often affected by E. histolytica?
- Cecum and ascending colon = most often
- Sigmoid, rectum, and appendix can also be affected
What does E. histolytica do in the colon?
Which characteristic ulcer may be seen?
Attach to colonic epithelium, induce apoptosis, invade crypts and burrow laterally into LP –> recruits neutrophils = tissue damage –> flask shaped ulcer
Somtimes E. histolytica may penetrate which vessles and embolize to which organ?
Causing what?
- Splanchnic vessels –> liver –> producing an abscess
- Abscess may exceed 10 cm in diameter w/ shaggy fibrin lining
Pts w/ E. histolytica infection present with what symptoms?
What are some complications which may occur in some?
- Abdominal pain, bloody diarrhea, and/or weight loss
- Acute necrotizing colitis and megacolon may occur
Where is Giardia lamblia infection endemic, due to cysts being resistant to what?
- Endemic in unfiltered public water supplies
- Cysts resistant to chlorine
Giardia lamblia cause what type of damage/problems in the GI tract?
- Decreased expression of brush-border enzymes (i.e., lactase)
- Microvillous damage and apoptosis of SI epithelial cells
- DO NOT invade
Which immune system components are important for the clearance of Giardia infection?
- Secretory IgA
- IL-6
Patients with what underlying disorders are often severely affected by Giardia lamblia?
- Immunosuppressed
- Agammaglobulinemia
- Malnourished
How is Giardia able to evade immune detection?
Continous mods of the major surface Ag -> Variant Surface Protein
Which characteristic features allow for identification of Giardia when looking at duodenal biopsies?
- Characteristic pear shape
- Presence of two equally sized nuclei
Infection by Giardia is usually detected with what method and samples from where?
Immunofluorescent detection of cysts in stool samples
Cryptosporidium are most commonly transmitted how?
Oocysts are resistant to?
- Contaminated drinking water
- Resistant to chlorine
Where in the world is Cryptosporidium found, what is the exception?
- Found worldwide
- Exception is Antartica, because oocysts are killed by freezing
Describe how ingested oocysts of Cryptosporidium are able to get into the small intestine?
- Oocyst releases sporozoites following activation of proteases by H+ (stomach)
- Sporozoites = motile –> special organelle for attaching to brush border and causes eneterocyte cytoskeleton changes
- Cause enterocyte to engulf the parasite; takes up residence in endocytic vacuole within microvilli
Presence of Cryptosporidium within an endocytic vacuole of microvilli leads to what?
Net effect?
- Sodium malabsorption + Chloride secretion
- Increased tight junction permeability
Net effect = non-bloody, water diarrhea
Although the sporozoite is intracellular, how does it appear using light microscopy?
Appears to sit on top of epithelial apical membrane
Where are the largest concentration of Cryptosporidium found in the GI?
Diagnosed how?
- Terminal ileum and Prox. Colon
- Diagnosed based on oocysts in stool!
How is the diganosis of the intestinal cestodes (tapeworms) made?
Proglottids and eggs in the stool
