Cholera Vignette

Question 1

Clinical Features

Answer 1

Severe acute watery diarrhea, V, AbP, Dehydration, Renal Failure, Low K and Ca, muscle pain/spasms, hypoglycemia, low bicarbonate, acidosis, coma

Question 2

Cholera Toxin A and B

Answer 2

Toxin A and B associate 1:5 A:B
B binds GM1 ganglioside R on apical membrane of mucosal cells and causes endocytosis of entire toxin complex.
A is activated following disuphide bond cleavage, stimulates Gx protein, activates AC, cAMP produced which turns on Cl transporter CFTR. Chloride exits into lumen, Na follows through shunt and draws water with it.

Question 3

Cystic Fibrosis Transmembrane Conductance Receptor

Answer 3

Activated by cAMP produced via cholera toxin A binding Gx protein and stimulating AC.
Possible heterozygote advantage with CFTR mutation would explain high CF carrier rate.

Question 4

Oral Re-hydration solution physiology

Answer 4

Oral re-hydration solutions contain glucose, carbohydrates, and salts. Glucose uptake by epithelia utilizes sodium co-transport secondary active transport which drives chloride and water reabsorption through leaky junction shunt.