GI tract Flashcards
are there more aerobic or anaerobic bact in the GI tract?
anaerobic (10^11 vs 10^8) respectively
most common aerobe in the GI tract?
E. coli
normal intestinal flora serves to…
protect us from infection with intestinal pathogens
how many different species are present in each individual’s GI tract?
500-1000
host’s non specific defenses agst GI pathogens
stomach acid, intestinal motility, intestinal flora
disease in stomach/small intestine is generally accompanied with…
bloating, nausea, vomiting and/or indigestion
what tpe of diarrhea is associated with pathogen in small intestine?
large-volume watery diarrhea, since 90% of the intestine’s capacity to adsorb liquid = in small intestine
disease in the colon is generally associated with
cramps, tenesmus (fecal urgency) and diarrhea that consists of frequent small-volume loss stools
a pathogen that does not cause fever, elevated WBC or high PMNs in stool is generally located where and how does it cause disease?
these organisms usually cause disease by the elaboration of toxins that induce cellular secretion or disrupt ion exchange (cholera toxin, heat-labile toxin) generally cause these effects in the small intestine
fever, elevated WBC and PMN in the stool generally indicate what about the org?
that they’ve invaded the intestinal epithelium or elaborate cytotoxins (eg clostridial toxins A and B) therevy causing structural damage to intestinal cells
bacterial diarrhea in the small intestine usually resolves itself within how many days? what about diarrhea of the colon?
small intestine: 2-3 days, colon: 5-7 days
C. diff disease
colitis, charcterized with: abdo cramping, leukocytosis (lots of WBCs– more than 20k for c diff) and high fevers
C. diff
gram stain/shape:
oxgen status:
spore forming?
C. diff
gram stain/shape: gram positive bacillis
oxgen status: obligate anaerobes
spore forming? yes- spores = highly resistant dormant forms of bact. that return to being active growing bacterium when nutrients are avb
where are c diff spores found? how are they spread?
widely in envt, but particularly in hospital, nurseries, nursing homes, bathrooms
spread: fecal/oral
risk factors for c diff
abx elderly age debilitated state PPIs GI surgery
how is c diff usually detected?
a test is performed for the cytotoxicity rather than culturing the organism
pathogenesis
organisms colonize the colon and cause a colitis, this may involve the formation of pseudomenbrane (psudomembranous colitis)
mechanism of C diff toxin A and Toxin B (TcdA and TcdB)
bind cell surface receptors —> receptor mediated endocytosis —>uptake toxin into endocytic vacuoles –> acidic pH triggers translocation of toxin into the cytosol —> acts as glucosyltransferase on cellular Rho GTPases (which are responsible for mntnc/modulation of cell structure, shape and mvmt– regulate dynamics of cellular actin cytoskeleton)—> inactivating them
what two things have allowed for a more virulent strain of C diff
- deletion mutation of TcdC gene that encodesa negative regulator of TcdA and TcdB. So these strains express Toxin A and B at higher levels
- the production of a third toxin called Binary Toxin which is encoded by the genes TcdA and TcdB and ADP ribosylates actin leading to dell death
pseudomembranes– what are they? what do they represent
they are an accumulation of necrotic tissue caused by toxin-induced necrosis of mucosal cells, which may involve the entire thickness of the mucosa during c diff. “Pseudomembranous colitis” is caused by a severe form of the disease from C diff
txt of C diff
metronidazole (flagyl) which is active agst anaerobes or vancomycin (active agst GP orgs). Vancomycin = poorly absorbed—> high conc. in GI lumen
*relapses are common (10-25%)- retreatment with the same/alt therapy = gen successful
Enterohemmorrhagic E coli (EHEC) disease
hemorrhagic colitis: watery diarrhea with intense abdo pain followed by bloody diarrhea. Pts generally afebrile
Hemolyttic uremic syndrome
what is it associated with?
what is it?
EHEC (8-11% of EHEC cases get it, primarily children less than 5yo)
1) microangiopathic hemolytic anemia
2) thrombocytopenia
3) thrombosis of the glomerular capilaries leading to acute renal failure
H antigen is a component of the…
flagellum
the O antigen is a component of
bacterial LPS
Detection of EHEC
by culture of stool combined with specific enzymatic tests
- culture of sorbitol non-fermenting orgs is combined with an enz immunoassay for the production of Stx toxin
Pathogenesis of EHEC (2 main routes)
1) organism colonizes the distal ileum/lg intestine –> attach to intestinal cells —>T3 secretion system (injectosome) leads to a pedestal
2) EHEC releases Stx1/2 toxins which gets into the cytoplasm of intestinal cells and modifies rRNA/blocks prot synth.
Type 3 secretion organelles are present in which enteric pathogns (4)?
- salmonella
- shigella
- pathogenic Ecoli
- Yersinia
Stx 1/2 toxins from EHEC mediate what two thing
1) capillary thrombosis associated with inflammation of the colonic epithelium that leads to hemorrhagic clitis
2. renal endothelial damage that leads to renal failure
Cholera toxin organism: toxin type: subunit: molecular mechanism/effect:
Cholera toxin organism: Vibrio cholerae toxin type: ADP ribosylating toxin subunit: AB molecular mechanism/effect: ADP ribosylation of G\_\_ activates host cell adenylate cyclase, which Increases cAMP ---> efflux of fluid/ions
Heat-labile toxin organism: toxin type: subunit: molecular mechanism/effect:
heat labile toxin organism: Enterotoxigenic E.Coli (ETEC) toxin type: ADP ribosylating toxin subunit: AB molecular mechanism/effect: ADP ribosylation of G\_\_ activates host cell adenylate cyclase, which Increases cAMP ---> efflux of fluid/ions
Heat-stable toxin organism: toxin type: subunit: molecular mechanism/effect:
heat stable toxin
organism: Enterotoxigenic E.Coli (ETEC)
toxin type: Guanylate cyclase activating toxin
subunit: single protein
molecular mechanism/effect: activates membrane bound guanylate cyclase— > increases cGMP and cGMP fluid secretion
Stx (formerly shiga toxin) organism: toxin type: subunit: molecular mechanism/effect:
organism: shigella dysenteriae
toxin type: RNA glycosidase
subunit: AB
molecular mechanism/effect: single-site depurination of rRNA –> inhib prot synth/cell death
Stx (formerly shiga-like toxin) 1 and 2 organism: toxin type: subunit: molecular mechanism/effect:
organism: EHEC
toxin type: RNA glycosidase
subunit: AB
molecular mechanism/effect: single-site depurination of rRNA –> inhib prot synth/cell death
txt of EHEC
No abx–
abx stress the bacteria –> increased expression of phage genes (and Stx toxins are within the phage, so increased production of Stx also occurs)
Salmonella disease– 3 types
1) gastroenteritis, 2) typhoid (enteric fever) and 3) occasionally sepsis
gastroenteritis caused by: manifestations: where is it located: what is found in the stool: how long does it last:
caused by: s. typhi or S paratyphi
manifestations: fever, mucoidy and watery diarrhea, abdo cramping, tenesemus (rectal urgency)
located: localized to small intestine– preceded with nausea/vomiting
stool: contains PMNs and sometimes RBCs
Lasts: 5 days (self-limiting)
typhoid (enteric) fever
caused by:
manifestations:
where is it located:
typhoid (enteric) fever
caused by: salmonella
manifestations: severe, prolonged dusease with systemic manifestations (fever, headache, rash, constipation or diarrhea, wt loss, general malaise, seeding of joints (infectious arthritis), meningitis, gall bladder or liver abcess
where is it located: systemic bacteremia
Sepsis from salmonella
salmonell in the blood stream– leads to seeding of multiple sites within the body
what two serovars cause typhoid fever?
Salmonella Typhi and Salmonella Paratyphi
salmonella is spread by
contamination of food, often involving poorly refrigerated prepared foods
In the Us. S typhi is found only in…
travelers and immigrants – more prevalent world wide
salmonella gram stain/shape
gram neg rods, closely related to E coli and Shigella
detection of salmonella is based on:
isolation of salmonella from stool —>macconkey agar is lactose negative and a more selective media such as salmonella-shigella agar
pathogenesis of salmonella
like Tb, salmonellae enter into cells and remain IC throughout the disease process.
Unlike Tb– have T3 injectosome for inducing bact. uptake so they enter phagocytic and non-phagocytic cells
Treatment of Salmonella caused gastroenteritis
gastroenteritis is self limiting, so with uncomplicated ifx– No ABX
mnage with fluid/electrolyte replacement
Txt for Typhoid (enteric)fever, caused by S. typhi or S. paratyphi
Abx therapy
Helicobacter pylori disease
chronic gastritis/peptic ulcer disease with nausea, anorexia, vomiting, or epigastric pain, often relieved by eating
chronic gastritis is a precursor of gastric adenocarcinoma and probably gastric lymphoma
transmission of H. pylori
fecal-oral, mother-child, oral-oral
H. pylori gram stain/shape
small curved microeaerophilic gram negative rods
they are highly motile with a polar flagellum that causes a corkscrew motion
3 useful diagnostic tests for H. pylori
1) serology for IgG to H. pylori Ag
2) breath test detects high urease activity of the org
3) stool Ag test
4) culture from endoscopy biopsy
- Ab persists for at least 9 mo after successful txt/ serology isn’t useful to see if it was cured post txt
pathogenesis of H pylori
infects stomach/proximal intestine using T4 secretion sys (CagA injected —> induces imm sys) —> chronic superficial gastritis —> can cause atrophic gastritis, intestinal metaplasia, dysplasia and subsequently gastric adenocarcinoma
specialized secretion system of H. pylori
type 4 secretion sys– delivers effector prot CagA into cytosol of gastric and duodenal epithelial cells, which induces an imune response in the tissue (very sig since the stomach is normally devoid of imm cells)
how does H pylori survive the acidic stomach envt?
it produces urease which cleaves urea into ammonia —> alkaline micro envt
– w/ chronic superficial gastritis, gastric epithelium slowly stop being able to produce acid
Txt of h pylori
compo of PPI and two Abx
