Cholera

Question 1

Clinical features of cholera infection

Answer 1

1. Voluminous (up to 1L/Hr) of watery feces with bits of mucus
2. Vomiting
3. Severe and rapid dehydration

Question 2

Role of cholera toxin A

Answer 2

one of two subunits (A and B)

• A subunit = active site
• gets cleaved off and endocytosed, binds to G protein, stimulates adenylate cyclase to produce cAMP

Question 3

Role of cholera toxin B

Answer 3

one of two subunits (A and B)

• B subunit = transport molecule
• binds to GM1 ganglioside receptor on surface of enterocyte

Question 4

Role of Cystic fibrosis Transmembrane Conductance Regulator (CFTR) in cholera infection - and describe Ctx action

Answer 4

cholera may select for those with only one good CFTR

-located on apical (luminal) side of membrane

1. Ctx bings to GM1 ganglioside receptor on enterocyte surface via B subunit
2. A subunit cleaved off and binds to G protein, which stimulates cAMP.
3. CFTR is activated by cAMP

–> overactivation of CFTR due to Ctx = massive efflux of Cl- ions (followed by water!)

Question 5

Describe physiology behind oral rehydration

Answer 5

OR takes advantage of Na transporters in the apical surface of the intestinal epithelia cell

1. couple glucose, or starch with Na -> drink -> ends up in the intestinal lumen.
2. promotes Na absorption thru apical membrane, which makes Cl- and water flow away from the lumen! (ie. GI tract)

Question 6

What are the two types of cholera that affects humans?

Answer 6

1. Vibrio Cholerae O1

2. Vibrio Cholerae O139

Question 7

We are currently in the ____ (number) cholera pandemic caused by _______ (type)

Answer 7

7th, V. cholerae O1

Question 8

How is Vibrio cholerae spread?

Answer 8

Fecal oral route

naw mean??

Question 9

What are the 3 toxins from V. cholerae that result in diarrhea?

Answer 9

1. ctx (cholera toxin) - primary player
2. zot (zonulin occludens toxin)
3. ace (accessory cholera enterotoxin)

Question 10

1. Cl- efflux is primarily thru what? 2. Located on which side?
2. Driven by what?

Answer 10

1. CFTR
2. on apical side
3. Driven by gradient produced by Na/K/Cl- cotransporter on basolateral side

Question 11

For funsies, what two flavors does diarrhea come in? And which one is Cholera?

Answer 11

1. osmotic
2. secretory - cholera type
   
   • intestines actively secreting fluids and electrolytes into lumen

Question 12

Functions of villi

Answer 12

fingerlike proj. in mucosa that increase absorptive capacity of intestine

Question 13

Functions of crypts

Answer 13

located at base of villi: secrete fluids and electrolytes

Question 14

zot (zonulin occludens toxin) function

Answer 14

an enterotoxin by Vibrio cholerae

ZOT activates a complex intracellular cascade of events – loosens the tight junctions

= “leaky” gut