Cholera Vignette

Question 1

Cholera symptoms

Answer 1

1. Severe, watery diarrhea
2. Low-grade fevers and drowsiness
3. Fatigue
4. Decreased urination and dehydration
5. Skin tenting without lesions
6. Tachycardia
7. Muscle cramps
8. Nausea, vomiting
9. Hypovolemic shock

Question 2

Treatment:

Answer 2

1. Oral rehydration therapy. Notice can also use IV rehydration.
2. Rehydrate, maintain hydration, feed early to make sure nutrition doesn’t get too poor.
3. Notice can use antibiotics (azithromycin) to quicken this process.

Question 3

Recall: the bacteria isn’t the problem, it’s the

Answer 3

toxin that the bacteria secrete.

Question 4

A subunit:

Answer 4

active site

Question 5

B subunit:

Answer 5

transport/bindng molecule

Question 6

B subunit binds to the

Answer 6

GM1 ganglioside receptor on enterocyte surface

Question 7

A subunit Binds to

Answer 7

cleaved off and endocytosed:

Gs proteins, inactivating their GTPase activity (thus always turned on) – stimulates production of cAMP.

Question 8

cAMP activates

Answer 8

CFTR (cystic fibrosis transport regulator) chloride channel in apical membrane.

Question 9

CFTR is in the ___ memebrane

Answer 9

apical

Question 10

Notice that the Na-K pump on the

Answer 10

basolateral side may also be shut down.

Question 11

Perpetual CFTR activation leads to

Answer 11

massive chloride efflux.

Question 12

The ______ draws water with it, causing diarrhea.

Answer 12

efflux of chloride

Question 13

Since the tight junctions in apical enteric cells are relatively loose, you can

Answer 13

lose a whole lot of water and sodium very quickly paracellularly as they follow the chloride.

Question 14

Effectively ORS is just

Answer 14

water, sugar, and salt (plus potassium and citrate in WHO formula).

Question 15

Homemade ORS:

Answer 15

8 teaspoons sugar, 1 teaspoon salt in one liter of water.

Question 16

How ORS works:

Answer 16

Small amounts can be absorbed quickly; small sips can rehydrate patients even when emesis follows.

Glucose helps Na+ uptake (and therefore water retention) in enteric system, also provides nutrition

Notice can replace glucose with rice powder, which may reduce severity of diarrhea by adding amino acids to improve sodium uptake in enterocytes (counteract Cl- and water efflux).

Question 17

Understand why someone with cystic fibrosis may be relatively protected from cholera symptoms.

Answer 17

Cystic fibrosis shuts down the CFTR receptors; heterozygotes for cystic fibrosis seem to be
partially protected from the effects of cholera toxin.

Question 18

Two types of cholera that affect humans:

Answer 18

1. Vibrio cholerae O1

2. Vibrio cholerae O139

Question 19

Vibrio cholerae O1 of which there are two subtypes

Answer 19

(Classical and El Tor). There are 3 serotypes of O1: Inaba, Ogawa and Hikojima.

Question 20

Vibrio cholerae O139 –

Answer 20

first described in Bangladesh in 1992, now considered endemic in the region.

Question 21

Vibrio cholerae is spread by the

Answer 21

fecal-oral route.

Question 22

________ is crucial to control cholera transmission..

Answer 22

Good sanitation

Question 23

The second messengers______ lead to chloride secretion through the _______.

Answer 23

Ca2+ and cAMP

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)

Question 24

Zonulin occludens toxin (Zot) is located on the______ and binds to a ______, resulting in an ________

Answer 24

bacterial membrane

Zot receptor

alteration of intestinal permeability through a cascade of intracellular events that lead to subsequent tight junction disassembly.

Question 25

Accessory cholera enterotoxin (Ace) affects the

Answer 25

potential differences across cells, contributing to the diarrhea, but the precise mechanism is still unknown.

Question 26

Antibiotics will

Answer 26

shorten the duration of disease and reduce the risk of further infectivity by killing the organisms.

Question 27

Anti-diarrheal medications are not indicated for cholera, as while it may slow down

Answer 27

intestinal motility, it will not affect the secretory component of the diarrhea (in fact, it may make you feel worse!)

Question 28

Zot is believed to mimic

Answer 28

Zonulin, the naturally occurring endogenous modulator of tight junctions. This results in an increased efflux of salt and water.

Question 29

Ctx binds to the

Answer 29

GM1 ganglioside receptor on surface of the enterocyte via the B subunit.

Question 30

the A subunit binds to G protein intracellularly, and then stimulates

Answer 30

adenylate cyclase to produce cAMP

Question 31

cAMP leads to the continuous activation of _____, resulting in a massive

Answer 31

CFTR

efflux of chloride ions, followed by water, resulting in massive watery diarrhea high in electrolyte content.