3.5 Pathogenesis of infective diarrhoea

Question 1

define intoxication

Answer 1

when a person ingests a toxin that has been produced outside of the body

Question 2

define infection

Answer 2

results when a pathogen inhabits the body and subsequently causes disease (only occurs when bacteria replicates in the body)

Question 3

What causes diarrhoea

Answer 3

either an altered movement in ions and water that follows an osmotic gradient

Question 4

What are the 6 mechanisms causing diarrhoea?

Answer 4

1. Increased Cl secretion (CFTR and CLCA)
2. Reduced Na absorption (NHE3)
3. Increased paracellular permeability
4. Reduced Cl absorption (DRA)
5. Reduced H2O absorption (aquaporins)
6. Reduced Na and glucose absorption (SGLT-1)

Question 5

What type of pathogen is vibrio cholera?

Answer 5

Gram negative, facultative anerobe, highly motile rod with a single polar flagella

Question 6

How does vibrio cholera infect people?

Answer 6

infect via the consumption of contaminated water/food

Question 7

What are the symptoms of vibrio cholera?

Answer 7

Acute watery diarrhoea with severe dehydration

Question 8

What is the treatment of vibrio cholera?

Answer 8

80% with oral rehydration salts, some may need IV fluids if severely dehydrated

May require antibiotics do diminish duration, reduce volume of rehydration

Question 9

What factors of vibrio cholera are essential for colonisation?

Answer 9

Pilus TCP (for adhesion) and GbpA

Question 10

What is the structure of vibrio cholera?

Answer 10

A subunit bound to a pentameric ring of B subunits

Question 11

What is the role of the B subunits in vibrio cholera?

Answer 11

deliver the A subunit into the cell to cause diarrhoea

Question 12

What is the function of the cholera toxin?

Answer 12

The A subunit of the cholera toxin causes increased Cl secretion and decreased Na absorption leading to an increase in NaCl levels in the lumen

Question 13

How does the cholera toxin A sub unit cause diarrhoea?

Answer 13

Activates adenylate cyclase which catalyses the conversion of ATP to cAMP increasing the activity of the chloride transporter and decreasing the activity of Na transporters

Question 14

What type of pathogen is Enterotoxigentic E.Coli?

Answer 14

Gram negative, facultative anaerobe, motile rod with many flagella

Question 15

How does Enterotoxigentic E.Coli cause infection?

Answer 15

Causes increased Cl secretion and decreased Na absorption by the heat stable toxin binding to guanylyl cyclase on small intestine epithelium catalysing GTP to cGMP increasing the activity of chloride (CFTR) and decreasing Na (NHE3) transporter

Question 16

What type of pathogen is Enterohaemorrhagic E.Coli?

Answer 16

Gram negative, facultative anaerobic rod

Question 17

What are the main sources of EHEC?

Answer 17

raw or undercooked ground meat products, raw milk and fecal contamination of vegetables

Question 18

What are the symptoms of EHEC?

Answer 18

Diarrhoea or bloody diarrhoea (haemorrhagic colitis/haemorrhagic uraemic syndrome)
Fever

Question 19

Do you use antibiotics for EHEC?

Answer 19

Not antibiotics because it will increase the risk of haemorrhagic uraemic syndrome

Question 20

What are the colonisation factors of EHEC?

Answer 20

Intimin and Tir

Question 21

How does EHEC cause infection?

Answer 21

the Tir receptor on the Intimin binds causing decreased surface area for nutrient absorption, causing increased osmolarity of the intestinal contents and malabsoprtion

Question 22

How do shiga toxins cause diarrhoea?

Answer 22

toxin A subunit inactivates ribosomes by inhibiting protein synthesis and causes apoptosis. toxin 1 and 2 inhibit absorption of water causing luminal fluid accumulation in the intestine

Question 23

What kind of pathogen is C. Difficile

Answer 23

Gram positive, spore forming rod

Question 24

What are the colonisation factors of C.Difficile?

Answer 24

S layer proteins
Cell wall protein
Fbp68
FliC-FliD components of flagella

Question 25

What are the toxins of C.difficile?

Answer 25

Toxin A: binds to apical side of host cell receptor causing direct alterations in barrier function and ion transport

Toxin B: gains access to the basolateral side of the cell after tight junction disruption

Binary toxin: destabalize cytoskeleton and potentiated toxicity of A and B increasing severity of infection

Question 26

How do toxin A and B of C.difficile cause infection?

Answer 26

glycosylate small GTPase Rho which leads to disruption of cytoskeletal integrity and cytotoxic effects. This initiates an inflammatory cascade that causes increased damage resulting in fluid release. The ENS nerves and toxin A will be activated and enhance production or release of neuropeptides which elicit chloride secretion in intestinal epithelial cells