C. difficile: apoptosis or necrosis?

[stronghold]

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What is the mechanism of toxin B (cytotoxin) of C. difficle? I have a note from UW that it's necrosis, while I have just got it wrong in Rx because they say it's apoptosis!!

 

[Phloston]

I had been annoyed by this when I was studying for Step1, but I currently teach my students necrosis.

The couple things I mention (apart from the obvious ones):

AB toxin test in stool is Dx, not stool culture.
C. difficile-mediated necrosis is through disruption of cytoskeleton via actin depolymerization.

You haven't taken the Step yet, so you're going crazy over small details, which is fine, but after you take the darn thing, you'll realize the most they'd ever ask you is, "which drug did this patient take?"

Btw, when is your exam?

 

[Transposony]

Apoptosis likely accounts for the mechanism of death in cells exposed to TcdA and TcdB.

Glucosylation of Rho GTPases by toxins A and B locks these proteins into an inactive conformation, thereby blocking all downstream signaling pathways in the cell. The result is disruption of the actin cytoskeleton, cell rounding and eventually apoptosis and death of the intoxicated cell.

 

[Transposony]

Robbins Basic Pathology 9th Ed, Page 584:

Toxins released by C. difficile cause the ribosylation of small GTPases, such as Rho, and lead to disruption of the epithelial cytoskeleton, tight junction barrier loss, cytokine release, and apoptosis.

So, C. difficile toxin directly causes apoptosis and indirectly causes (secondary) necrosis & inflammation via cytokine release.

 

[Phloston]

Glad you posted Robbin's here for comparison.

Stanford University School of Medicine is teaching its students necrosis (http://surgpathcriteria.stanford.edu/gi/pseudomembranous-colitis/printable.html).

I'd say Transposony's statement about the toxin directly causing apoptosis is accurate, as per Robbin's, but if you look at the colon itself and ask for what is responsible for most of the visible cell death, it's necrosis.

For the USMLE, I'd say necrosis (if they'd ever ask it).

 

[stronghold]

Thank you guys! Phloston check your messages