Chapter 17 part 7--small intestine organisms Flashcards
Yersenia
- Yersinia enterocolitica and Yersenia pseudo tuberculosis
- occurs through contaminated pork, milk, or water
- Yersinia pestis–bubonic plague
Pathogenesis of Yersinia
- invades M cells using bacterial adhesions to bind to host cell B1 integrins
- Bacterial iron uptake system increases Yersinia virulence and systemic dissemination
- Patients with hemolytic anemia or hemochromatosis are likely to become septic and die
Morphology of Yersenia
-preferentially invades the ileum, appendix, and right colon; organisms proliferate in lymph nodes resulting in regional nodal hyperplasia and overlying mucosa can become hemorrhagic and ulcerated
Clinical features of Yersenia
-Abdominal pain, fever, and diarrhea can occur (mimicking appendicitis)
Extra intestinal manifestations of Yersinia
- common
- pharyngitis, arthralgia and erythema nodosum
Post-infectious complications of Yersenia
- sterile arthritis
- Reiter syndrome
- myocarditis
- glomerulonephritis and thyroiditis
Escherichia coli
- gram-negative bacilli that colonize the normal GI tract
- most are nonpathogenic but a subset (classified by morphology, in vitro characteristics and pathogenesis) cause disease:
- ETEC, EPEC, EHEC, EIEC, EAEC
Enterotoxigenic E. coli (ETEC)
- spread in contaminated food or water and are the chief cause of traveler’s diarrhea
- produce heat-stable toxin that increases intracellular cyclic guanosine monophosphate (cGMP) or a heat-labile choleralike toxin that increases intracellular cAMP
- both cause chloride and water secretion and inhibit epithelial fluid absorption leading to a noninflammatory watery diarrhea
Enterohemoryhagic E. coli (EHEC)
- spread in contaminated meat, milk, and veggies and produce a shiva-like toxin
- clinical symptoms and morphology resemble infections with Shigella dysenteriae
- 2 major serotypes: O157:H7 and non-O157:H7
- O157:H7 is more likely to cause large outbreaks, dysentery and HUS
Enteroinvasive E Coli (EIEC)
- bacteriologically akin to Shigella
- Although not toxin producing, they invade epithelial cells and cause an acute, self-limited colitis
Enteroaggregative E. Coli (EAEC)
- attach to epithelium by adherence fimbriae aided by a bacterial dispersion that neutralizes the negative surface charge of lipopolysaccharide
- produce a shigalike toxin but typically cause only a non bloody diarrhea
Pseudomembranous colitis
- formation of adherent inflammatory pseudomembranes overlying sites of mucosal injury
- classically caused by overgrowth-and-toxin production by Clostridium Difficile after competing bowel organisms have been eliminated by antibiotics
Other organisms that cause PMC
-Salmonella, Clostridium perfringes, Staph aureus
Morphology of pseudomembranous colitis
- epithelial denudation with plaque like adhesion of fibrinopurulent-necrotic, gray-yellow debris and mucus
- Pseudomembrane is not specific and can form with any severe mucosal injury (e.g., ischemia or necrotizing infections)
Clinical features of pseudomembranous colitis
- C. difficile is prevalent in hospitals
- 30% of hospitalized patients can be colonized (vs. 3% of general population)
PMC presentation, Dx and Tx
- fever, leukocytosis, crampy abdominal pain and watery diarrhea
- toxin detection in stool yields definitive diagnosis
- Tx= metronidazole or vancomycin
- 40% incidence of recurrent infection after treatment
Whipple Disease
-rare, systemic condition caused by gram-positive actinomycete Tropheryma whipplei
Whipple Disease presentation
- diarrhea, weight loss, malabsorption
- Extraintestinal manifestations (due to bacterial spread) include arthritis, fever, lymphadenopathy, and neurologic, cardiac, or pulmonary disease
Gross morphology of Whipple Disease
-marked villous expansion in small bowel, imparting a shaggy appearance to mucosal surface
Microscopic morphology of Whipple Disease
- dense accumulation of distended foamy macrophages in small intestine lamina propria–these ells are stuffed with PAS-positive bacteria within lysosomes
- Laden macrophages present in lymphatics, lymph nodes, joints and brain
- Active inflammation is absent
Recap–Causes of infectious enterocolitis
- Cholera
- Campylobacter
- Shigella
- Salmonella
- Typhoid fever
- Yersenia
- E. Coli
- PMC
- Whipple Disease
- Viral Gastroenteritis
- Parasitic Enterocolitis
Re-cap–causes of malabsorption and Diarrhea
- CF
- Celiac Disease
- Environmental Enteropathy
- Autoimmune Enteropathy
- Lactase Deficiency
- Abetalipoproteinemia
Causes of Viral Gastroenteritis
- Norovirus
- Rotavirus
- Adenovirus
Norovirus
- Norwalklike virus
- single stranded RNA virus
- accounts for half of all gastroenteritis outbreaks in world
- Local outbreaks due to contaminated food or water but person-person transmission underlies most sporadic cases
Symptoms of Norovirus
- Immunocompetent patients=self-limited watery diarrhea, often with abdominal pain, nausea and vomiting
- Biopsy morphology non-specific
Rotavirus
- Encapsulated segmented double stranded RNA virus
- most common cause of severe childhood diarrhea
- readily spread bw people
- minimal infective inoculum is 10 particles
Rotavirus infects what cells?
- selectively infects and destroys mature small intestine enterocytes and epithelium is repopulated with immature secretory cells
- net secretion of water and electrolytes is compounded by malabsorption and osmotic diarrhea
Adenovirus
- second most common cause of pediatric diarrhea
- present with self-limited diarrhea, vomiting and abdominal pain
- histo=non-specific
Parasitic Enterocolitis
- common organisms:
- Ascaris lumbricoides
- Strogyloides
- Necator duodenal and Ancylostoma duodenale
- Enterobious vermicularis (pinworms)
- Trichuris trichina (whipworms)
- Schistosoma
- Intestinal cestodes (tapeworms)
- Diphyllobothrium datum
- Entamoeba histolytica
- Giardia lambda
- Cryptosporidium
Ascaris lumbricoides
- infects over billion ppl worldwide
- fecal-oral transmission followed by intestine-liver-lung-intestine life cycle
- Systemically disseminated larvae can cause hepatic abscesses or pneumonitis
- adult from masses induce an eosinophil-rich inflammation that can physically obstruct the intestine or biliary tract
- Dx by detecting eggs in stool
Stronyloides
- larvae in focally contaminated soil penetrate unbroken skin, migrate to lungs (where they cause inflammation) and then mature into adult worms in GI tract
- Eggs hatch in intestine and luminal larvae can penetrate mucosa causing auto infection
- induces strong eosinophil responses!
Nectar duodenale and Ancylostoma duodenale (hookworms)
- billions of ppl infected
- life-cycle begins with larval penetration through skin and subsequent maturation in lung
- after migration to trachea, they are swallowed
- worms then attach to duodenal mucosa and extract blood causing mucosal damage and iron-deficiency anemia
Enterobius vermicularis (pinworms)
- fecal-oral transmission
- do not invade host tissue and entire life cycle transpires in intestinal lumen, they rarely cause serious illness
- Adult worms migrate at night to anal orifice where eggs are deposited causing intense irritation and pruritis
Trichuris triciuria (whipworms)
- primarily infect children
- no tissue invasion but heavy manifestations can cause bloody diarrhea and rectal prolapse
Schistosoma
- adult worms reside within mesenteric veins
- trapped eggs in mucosa and submucosa induce a granulomatous response with bleeding and obstruction
Intestinal cestodes (tapeworms)
- infections occur by ingesting raw or undercooked fish, pork, or other contaminated meats
- Parasites reside within lumen without tissue invasion
- a codex attaches to mucosa, and proglottids contain eggs that shed in feces
D. latum
- fish tapeworm
- compete for host dietary vitamin B12 and cause B12 deficiency with megaloblastic anemia
Entamoeba histolytica
- fecal-oral transmission
- Infection occurs by ingesting acid-resistant cysts
- released trophozoites colonize colonic epithelium and reproduce under anaerobic conditions
- Dysentery results when amoebae induce colonic epithelial apoptosis, invade into lamina propria, and attract neutrophils
- Subsequent damage yields classic flask-shaped ulcer with narrow neck and broad base
Entamoeba histolytica–amoeba can also embolize to? Tx?
- liver–producing abscesses in over 40% of infected individuals
- Metronidazole targets organism-specific enzyme pyruvate oxidoreductase
Giardia Lamblia
- Flagellated protozoan and most common pathogenic parasitic infection in humans
- cysts are ingested from focally contaminated water or food
- duodenal trophozoites exhibit characteristic morphology (pear-shaped and binucleate!!!)
Giardia invasion? How does it cause damage?
- does not invade tissue but secrete products that damage the microvillus brush border and cause malabsorption
- Secretory IgA and mucosal IL-6 needed for clearance so immunocompromised severely affected
How do Giardia persist for prolonged duration in Immunocompromised hosts?
-through continuous modification of their major surface Ag
Cryptosporidium
- cause self-limited diarrhea in immunocompetent hosts but can cause chronic diarrhea in IC
- contaminated drinking water=transmission
- as few as 10 oocytes can cause Dz
- Stomach acid activates proteases that release motile sporozoites which are subsequently internalized by absorptive enterocytes
What causes the watery diarrhea seen in cryptosporidium infection
-Sodium malabsorption, chloride secretion and increased epithelial permeability responsible for ensuing watery diarrhea
Irritable Bowel Syndrome
- chronic, relapsing abdominal pain, bloating, and changes in stool frequency or form
- most common in females aged 20-40
- results from interplay of psychologic stressors, diet, and abnormal GI motility, perhaps via disruption of signaling in brain-gut axis
Inflammatory Bowel Disease
- results from inappropriate mucosal immune responses to normal gut flora; comprises two disorders:
- Ulcerative colitis
- CD (regional enteritis)
Ulcerative colitis
- severe ulcerating inflammation extend into mucosa and submucosa
- limited to colon and rectum
CD (also called regional enteritis)
-typically transmural inflammation, occurring anywhere in GI tract
Epidemiology of IBD
- more common in women–in teens/20s
- more common in developed countries leading to hygiene hypothesis
Hygiene hypothesis
-reduced frequency of enteric infections results in inadequate development of mucosal immune regulation
Pathogenesis of IBD
-results from combo of defects in host interactions with GI flora, intestinal epithelial dysfunction and aberrant mucosal immunity!!
Current model of pathogenesis of IBD
- transepithelial flux of microbes activates innate and adaptive immune responses
- In susceptible host, subsequent TNF release and other inflammatory signals increase tight junction permeability
- establish a self-amplyfing cycle of microbial influx and host immune responses that ultimately culminate in IBD
Genetics of IBD
- most genes are shared bw UC and CD
- familial clustering and concordance of monozygotic twins is 50% for CD and 50% for UC
What gene polymorphisms is associated with CD? What does it encode?
- NOD2 (nucleotide oligomerization binding domain 2)
- encodes a protein that binds to intracellular bacterial peptidoglycan and subsequently activates NF-kB
- Disease associated NOD2 variants are less effective are recognizing and combating microbes which enter lamina propria and trigger greater inflammatory responses
- Other genes also related to microbial recognition and regulate immune responses
Mucosal immune responses
- In CD, helper T cells are polarized to produce TH1 cytokines
- TH17 cells may also be contributory and polymorphisms in the IL-23 receptor (regulating TH17 cell development) may be protective
What cytokines are associated with IBD pathogenesis
-TNF, IFN-y, and IL-13 and immunoregulatoriy molecules like IL-10 and TGF-B also contribute to IBD pathogenesis
Mutations in what are linked to severe, early onset IBD?
-Autosomal recessive mutations of IL-10 and IL-10 receptor
Epithelial cell defects in IBD
-Barrier dysfunction, including defects in epithelial tight junctions, transporter genes, and polymorphisms in extracellular matrix proteins or metalloproteinases are associated with IBD
Microbiota
-Composition of the GI flora, and in particular those organisms that populate the intestinal mucus layer may influence pathogenesis by affecting innate and adaptive immune responses
Treatment of IBD
-Antibiotics can be helpful in managing IBD
