Gastro Block 7: Malabsorption and Oral Rehydration

List the 4 types of diarrhea:

1. hypermotility

2. osmotic

3. defective transport

4. secretory

What is Hypermotility Diarrhoea?

• the transport of water in the gut is too fast for absorption

What 2 things can cause hypermotility diarrhoea?

1. caused by a high fibre diet

2. caused by diabetes - adrenergic (high levels of glucose)

What is Osmotic diarrhoea?

• non-solute absorption (enzyme deficiency/villous atrophy)

What are the 2 causes of osmotic diarrhoea?

• lactase deficiency

• coeliac disease

What is defective transport diarrhoea?

• Na+ or Cl- transporters are absent

What causes defective transport diarrhoea?

• sodium/chloride diarrhoea is caused by rare congenital defects

What is secretory diarrhoea?

• net secretion from epithelium is more than net absorption

Give 4 causes of secretory diarrhoea:

1. inflammatory cytokines, blood hormones = pancreatic tumours secrete VIP or thyroid tumours secrete calcitonin

2. enterotoxins

3. viruses

4. parasites

What is travellers’ diarrhoea?

• diarrhoea caused by consuming food or water contaminated with bacteria, viruses or parasites while visiting new areas

• 80-90% of cases are bacterial (most commonly E.coli)

Give a bacterial, viral and parasitical cause of travellers’ diarrhoea:

1. vibrio cholerae

2. rotavirus

3. giardia intestinalis

How many deaths are there per year attributed to diarrhoeal disease globally:

1.17 million deaths

How much fluid to people with cholera lose per day and what is the mortality rate?

• 10 to 20 L per day

• 20-80% mortality if there is no treatment

Where is cholera endemic too and how does it infect people?

• cholera is endemic to asian waters

• cholera is comma shaped, flagellated so swims through the mucus barrier coming close to the intestinal epithelium lining

• secretes a toxin

List the 2 types of cholera:

1. Vibrio cholerae El Tor

2. Vibrio cholerae classical

What is special about vibrio cholerae El Tor?

• higher and more rapid transmission rates

• increased environmental persistance

• greater survivability within the host

Explain how the cholera bacteria attach to the mucosa

1. cholera use flagella to propel themselves through thick mucus layer of mucosa

2. bacteria use toxin coregulated pili to stick to surface of intestinal epithelial cells

Once attached to the mucosa what do the cholera bacteria do?

• the bacteria secrete AB toxin

• the ‘B’ sub-units bind to specific GM1 receptors on the surface of intestinal cells

• this triggers the cell to pull the toxin inside via endocytosis

• toxin travels through golgi apparatus → ER

Once the cholera bacteria is inside the epithelial cell what happens?

• the active ‘A’ subunit leaves ER via a translocon and goes to cytoplasm

• A sub unit tethers to Adenylyl cyclase which becomes permanently activated → dramatic rise in cAMP

• cAMP opens CFTR channels and Cl- ions leave out into intestinal lumen, sodium follows

• water follows in order to maintain osmotic balance

List forms of oral rehydration therapy:

• sodium chloride

• potassium chloride

• trisodium citrate

• dihydrate (converted to bicarb in liver)

• glucose

• sterilised water

Describe the self-limiting nature of cholera infection:

Vibrio cholerae is not an invasive bacterium; it doesn't enter the bloodstream (which would cause sepsis). It stays in the "lumen" (the hollow part) of the intestine.

Do you need to give antibiotics for patients with cholera?

• no - could be viral or parasitical infection

• Once the "poisoned" cells are replaced (the 5-day cycle), and the source of the bacteria is flushed out, the body recovers on its own.