Cholera Vignette Flashcards
- Recognize key clinical features of cholera infection.
- Describe the role of cholera toxin A and B and the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in cholera infection.
- Describe the physiology behind oral rehydration solutions.
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What are the key clinical features of cholera infection?
- Voluminous (up 1 liter per hour) watery feces with bits of mucus - this is sometimes called ‘rice water’ stools since it looks like water in which rice has been washed
- Vomiting
- Severe and rapid dehydration
What are the three genes (toxins) encoded by V. cholerae (the so-called “virulence cassette”)
- ctx (cholera toxin)
- zot (zonulin occludens toxin)
- ace (accessory cholera enterotoxin)
Ctx consists of an ___ subunit and ___ subunit. The A subunit is _____ while the B subunit is the ____.
A; B; active; transport molecule
What secretory channel is targeted by ctx? Where is it located?
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), located on the apical (luminal) side of the cells.
How does Ctx gain access to the intestinal crypt cells (secretory cells) that it targets?
Ctx binds to the GM1 ganglioside receptor on surface of the enterocyte via the B subunit. At the cell surface, the A subunit is then cleaved off and endocytosed.
Once inside the cell, how does the A subunit of Ctx generate massive diarrhea?
The A subunit binds to G protein intracellularly, and stimulates adenylate cyclase to produce cAMP. cAMP leads to the continuous activation of CFTR, resulting in a massive efflux of chloride ions, followed by water, resulting in massive watery diarrhea high in electrolyte content.
What does the zot toxin do?
Zot makes the tight junctions leaky.
[Zonulin occludens toxin (Zot) is located on the bacterial membrane and binds to a Zot receptor, resulting in an alteration of intestinal permeability through a cascade of intracellular events that lead to subsequent tight junction disassembly. It is believed to mimic Zonulin, the naturally occurring endogenous modulator of tight junctions.]
What about ace?
Accessory cholera enterotoxin (Ace) affects the potential differences across cells, contributing to the diarrhea, but the precise mechanism is still unknown.
Infection with V. cholera is a classic example of ____ diarrhea. _____ is the more common type of diarrhea.
secretory; osmotic
Are anti-diarrheal medications indicated? What about antibiotics?
No, anti-diarrheal meds are not indicated; Antibiotics are used only in very severe cases.
[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]
What is the fundamental principle behind oral rehydration therapy?
The fundamental principle of oral rehydration solutions is to take advantage of the sodium transporters in the apical surface of the intestinal epithelial cell. This is done by coupling glucose or starch with sodium in the intestinal lumen, to promote sodium absorption and hence chloride and water flow away from the lumen.
What specific mechanism of the oral rehydration solution allows resorption of Cl-/H2O/Na in the gut to alleviate diarrhea?
The WHO formulas take advantage of the sodium cotransporters on the apical side of the enterocyte, which are not affected during a cholera infection. These are in the form of sodium-glucose transporters, or sodium coupled with other substrates such as amino acids, which help in sodium reabsorption. Again, when sodium reenters a cell, chloride and water will then follow.
What is the formula for a SSS homeade solution?
Sugar and Salt Solution (SSS) can be homemade with 8 level teaspoons of sugar, ½ level teaspoon of salt, and 1 liter of clean water.
What is the infectious dose for V. cholerae?
The infectious dose of V. cholera is stated to be 10^4 to 10^8 cfu. (Lots)
