Cholera

Question 1

What is the clinical presentation of cholera?

Answer 1

• Diarrhea - rice water stools with up to 5+ bm/hr
• Dehydration
• Skin turgor (tenting)
• Vomiting
• Low grade fever
• Fatigue
• Low/no urine output

Question 2

What are the subunits of the Cholera Toxin (CT)? and what are their functions?

Answer 2

A & B subunits
A: active site
B: transport molecule

Question 3

How does CT enter the cell?

Answer 3

CT binds to GM1 ganglioside receptor on surface of enterocyte (with B subunit)
A subunits is cleaved and endocytosed

Question 4

What occurs once CT has entered the cells?

Answer 4

A subunit binds G protein-> stimulates adenylate cyclase to produce cAMP
cAMP-> activates CFTR (continuously)
when CFTR is activated=> continuous efflux of Cl- ions (followed by water)
DIARRHEA (with dangerously high electrolyte content)

Question 5

What type of diarrhea does Cholera cause?

Answer 5

Secretory diarrhea

Question 6

What is the other type of diarrhea?

Answer 6

osmotic diarrhea

Question 7

What causes osmotic diarrhea? How does it present?

Answer 7

Caused by osmotically active agent in intestinal lumen pulling water into the intestine
(i.e. lactose intolerance)
Also occurs in setting of malabsorptive conditions (i.e. celiac disease, gastroenteritis)
Last cause can be medications (i.e. polyethylene glycol used to treat consitpation)

Stool osmotic gap >100mOsm/kg

Improves with removal of osmotic source

Question 8

What caused secretory diarrhea? How does it present?

Answer 8

Watery stools continue even if patient is fasting

Caused by INTESTINE actively secreting fluids and electrolytes into lumen
i.e. cholera

Stool osmotic gapt < 50mOsm/kg

Question 9

What is the treatment of cholera?

Answer 9

Rehydration 
with a focus on volume repletion and electrolyte replacement
IV (if available)
ORT (pre-packaged or homemade)
(usually no antibiotics)

Question 10

Why are anti-diarrheal medications not good for Cholera?

Answer 10

They slow intestinal motility, without affecting secretory pathway => may worsen!

Question 11

How does ORT work?

Answer 11

By taking advantage of Na+ transporters on apical surface of intestinal epithelial cells:

• couple Na with glucose/ starch-> promote absorption
• Can reduce volume of diarrhea

Question 12

What does pre-packaged ORT contain?

Answer 12

NaCl - sodium chloride: 2.6g
Bicarb - trisodium citrate dehydrate: 2.9g
KCl - potassium chloride: 1.5g
sugar - anhydrous glucose: 13.5g
with 1L of CLEAN water

Question 13

What is the alternative, homemade preparation?

Answer 13

8t sugar
1/2t salt
1L clean water

Question 14

What is the benefit of a rice or cereal based ORT?

Answer 14

add substrate to the gut without increasing osmolality
=> provide additional glucose molecules for
glucose mediated absorption

+ amino acids may provide substrates for cotransport mechanisms within colon