Cholera Vignette Flashcards
Cholera symptoms
- Severe, watery diarrhea
- Low-grade fevers and drowsiness
- Fatigue
- Decreased urination and dehydration
- Skin tenting without lesions
- Tachycardia
- Muscle cramps
- Nausea, vomiting
- Hypovolemic shock
Treatment:
- Oral rehydration therapy. Notice can also use IV rehydration.
- Rehydrate, maintain hydration, feed early to make sure nutrition doesn’t get too poor.
- Notice can use antibiotics (azithromycin) to quicken this process.
Recall: the bacteria isn’t the problem, it’s the
toxin that the bacteria secrete.
A subunit:
active site
B subunit:
transport/bindng molecule
B subunit binds to the
GM1 ganglioside receptor on enterocyte surface
A subunit Binds to
cleaved off and endocytosed:
Gs proteins, inactivating their GTPase activity (thus always turned on) – stimulates production of cAMP.
cAMP activates
CFTR (cystic fibrosis transport regulator) chloride channel in apical membrane.
CFTR is in the ___ memebrane
apical
Notice that the Na-K pump on the
basolateral side may also be shut down.
Perpetual CFTR activation leads to
massive chloride efflux.
The ______ draws water with it, causing diarrhea.
efflux of chloride
Since the tight junctions in apical enteric cells are relatively loose, you can
lose a whole lot of water and sodium very quickly paracellularly as they follow the chloride.
Effectively ORS is just
water, sugar, and salt (plus potassium and citrate in WHO formula).
Homemade ORS:
8 teaspoons sugar, 1 teaspoon salt in one liter of water.
How ORS works:
Small amounts can be absorbed quickly; small sips can rehydrate patients even when emesis follows.
Glucose helps Na+ uptake (and therefore water retention) in enteric system, also provides nutrition
Notice can replace glucose with rice powder, which may reduce severity of diarrhea by adding amino acids to improve sodium uptake in enterocytes (counteract Cl- and water efflux).
Understand why someone with cystic fibrosis may be relatively protected from cholera symptoms.
Cystic fibrosis shuts down the CFTR receptors; heterozygotes for cystic fibrosis seem to be
partially protected from the effects of cholera toxin.
Two types of cholera that affect humans:
- Vibrio cholerae O1
2. Vibrio cholerae O139
Vibrio cholerae O1 of which there are two subtypes
(Classical and El Tor). There are 3 serotypes of O1: Inaba, Ogawa and Hikojima.
Vibrio cholerae O139 –
first described in Bangladesh in 1992, now considered endemic in the region.
Vibrio cholerae is spread by the
fecal-oral route.
________ is crucial to control cholera transmission..
Good sanitation
The second messengers______ lead to chloride secretion through the _______.
Ca2+ and cAMP
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
Zonulin occludens toxin (Zot) is located on the______ and binds to a ______, resulting in an ________
bacterial membrane
Zot receptor
alteration of intestinal permeability through a cascade of intracellular events that lead to subsequent tight junction disassembly.
Accessory cholera enterotoxin (Ace) affects the
potential differences across cells, contributing to the diarrhea, but the precise mechanism is still unknown.
Antibiotics will
shorten the duration of disease and reduce the risk of further infectivity by killing the organisms.
Anti-diarrheal medications are not indicated for cholera, as while it may slow down
intestinal motility, it will not affect the secretory component of the diarrhea (in fact, it may make you feel worse!)
Zot is believed to mimic
Zonulin, the naturally occurring endogenous modulator of tight junctions. This results in an increased efflux of salt and water.
Ctx binds to the
GM1 ganglioside receptor on surface of the enterocyte via the B subunit.
the A subunit binds to G protein intracellularly, and then stimulates
adenylate cyclase to produce cAMP
cAMP leads to the continuous activation of _____, resulting in a massive
CFTR
efflux of chloride ions, followed by water, resulting in massive watery diarrhea high in electrolyte content.
