Cholera Vignette

Question 1

Cholera symptoms

Answer 1

Voluminous stools (rice water) (1L/hour)
Vomiting
Severe and rapid dehydration (can die w/in hours w/o treatment)
Skin turgor (pinch and stays)

Question 2

Cholera toxin

Answer 2

A (active site) and B subunit (trasnport molecule, binds to GM1 receptor). Crypt cells.

Question 3

Mechanism

Answer 3

Toxin –> secondary messengers (Ca and Camp), Cl secretion via CFTR (into luminal side of cells). Cl should normally be driven by na/k/2cl cotransporter.
B subunit binds GM1. A is cleaved off and endocytosed. Binds G and stimulates cAMP production.
Get continuous CFTR activation. water follows chloride. Na follows.

Also ZOT toxin loosens tight J, more leaky gut.

Question 4

Osmotic vs. secretory diarrhea

Answer 4

Osmotic: mlc pulls H20 into intestine (lactose, drug, celiac). Remove the mlc- it’s better.
Secretory: Intestine activity secreting fluid/electrolytes, no improvement w/ removing mlc. This is cholera.

Question 5

Villi and crypt

Answer 5

Villi absorb and crypt cells secrete. Normally absorb > secretion, cholera it is not. Get net fluid/electrolyte secretion.

Question 6

ORT

Answer 6

Take advantage of Na transporters on apical side of intestine (they put Na into the cells)
Couple glucose/startch with Na to promote Na absorption and get Na/Cl to flow out of the lumen back into the cells.

Question 7

Lower osmolarity formula?

Answer 7

Want na: glucose 1:1… otherwise could cause pt to develop osmotic diarrhea.

Question 8

ORT and cotransporters

Answer 8

It uses Na/glucose or Na/AA transporters.
Solute coupled Na transporters.
Rely on Na/K pump on basolateral mem to create gradient that favors Na entry.
If you bring Na into the cell Cl- and thus H20 follow.