MET 2 - A Gut Feeling

Question 1

What happens if you lose too much bicarbonate in the gut?

Answer 1

Metabolic acidosis

Question 2

What does ORT do for diarrhoea, why is it effective?

Answer 2

In diarrhoea you only need to replace fluid loss because it corrects itself

Sodium and glucose transporter is not affected by the cholera toxin

K+ is given to correct hypokalaemia

Question 3

What symptoms does low K+ cause?

Answer 3

Muscle cramping and weakness

Arrhythmias

Question 4

What are treatments of cholera except ORT?

Answer 4

Antimotility agents
Antibiotics
Treat underlying cause of diarrhoea
Oral vaccines

Question 5

Explain the absorption of water, ions and solutes in the small intestine

Answer 5

Basolateral Na+/K+ ATPase pumps Na+ out of the cell into the capillary (low intracellular Na+)

Na+/glucose (SGLT) in the apical membrane uses the downhill Na+ gradient and Na+ and glucose are cotransported into the cell

Glucose then leaves the cell through the GLUT2 transporter via facilitated diffusion

The Low Sodium Gradient = low osmotic gradient
Water diffused into the cell via transcellular pathways (across membrane) or paracellularly (between enterocytes)

Question 6

Define diarrhoea.

Answer 6

Frequent bowel evacuation with passage of abnormally soft or liquid faeces (1/2)

Daily passage of more than 250 grams faeces (1/2)

Question 7

Give four processes that require the presence of water in the lumen of the small intestine

Answer 7

1⁄2 for each:
 hydrolysis reactions of digestion
 facilitation of absorption (brings products of digestion into close proximity to
microvilli)
 facilitation of propulsion of gut contents
 combination with mucin granules to make mucus

Question 8

What is the ion channel indirectly activated by cholera toxin? Exactly where is this channel located?

2 marks

Answer 8

CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) OR Chloride channel (1⁄2).

Channel is located on the apical membrane of epithelial cells (enterocytes) lining the intestinal crypts (of Lieberkuhn) (1⁄2 for each).

Question 9

Detailing (i) the cellular mechanism and (ii) the underlying forces at play: Explain how activation of the CFTR channel causes secretory diarrhoea.

(3 marks)

Answer 9

Opening of CFTR Cl- channel allows chloride ions to pass from epithelial cell into ‘lumen’ (1).

Na+ follows passively by paracellular pathway to balance the electrical gradient (1).

Increased presence of NaCl in lumen creates osmotic gradient driving movement of water into gut lumen (1).

Question 10

Which route does sodium take when it enters the lumen? Using your knowledge of body fluid compartments explain why.

2 marks

Answer 10

Sodium travels via the paracellular pathway (1).

Sodium comes from the interstitial fluid

(Sodium does not come from whithin the enterocytes - body cells contains very little sodium).

Question 11

What is the mechanism of action of cholera?

Answer 11

Vibrio cholerae releases cholera toxin

Bacteria stays in the lumen and binds to the apical surface

The toxin penetrates into the enterocytes

The toxin locks a G protein in the cytosol that stimulates adenylyl cyclase to continually produced cAMP

Increased cAMP levels prolong opening of CFTR channels
Increased chloride is secreted into the lumen

Sodium follows paracellularly and water follows the osmotic gradient passively

= profuse watery diarrhoea

Question 12

What causes osmotic diarrhoea?

Answer 12

Laxatives
Malabsorption (e.g. coelic disease)
Food intolerance (e.g. lactose staying in the lumen because no lactase)

Question 13

What causes secretory diarrhoea?

Answer 13

Cholera infection
Enterotoxigenic E coli (traveller’s diarrhoea)
Bile acid malabsorption

Question 14

Define: diarrhoea

Answer 14

Frequent bowel evacuation of abnormally soft and liquid faeces
Daily passage of more than 250g
3x a day of loose stools

Question 15

What happens to the fluid that enters the Small Intestine?

Answer 15

80% of the liquid is absorbed by the time you get to the large intestine

Tight relationship between water and solute absorption

Question 16

What route does Na+ take when entering the lumen? Using your knowledge of body compartments to explain why?

Answer 16

Sodium travels paracellularly and comes from the interstitial fluid

Sodium does not come from the enterocytes because body cells contain very little sodium

Question 17

Define osmotic diarrhoea

Answer 17

When large amounts of osmotically active (non absorbed) solutes are retained in the lumen

Water stays in the lumen

Due to malabsorption or ingesting poorly absorbed substances

Question 18

Define: secretory diarrhoea

Answer 18

Excessive secretion of electrolyte and water into the lumen due to inhibition or overactivaion of the enzymes in the enterocytes

Question 19

What is inflammatory diarrhoea?

Answer 19

Inflammation leading to the destruction of enterocytes

Direct loss of fluid and blood and reduced absorption of water

Question 20

What causes inflammatory diarrhoea?

Answer 20

IBD (Crohns, ulcerative collitis)
Campylobacteriosis, salmovellosis
Viral gastroenteritis

Question 21

What type of bacteria causes chloera? What is its name?

Answer 21

Vibrio cholerae

Grame negative

Question 22

What four process require water in the lumen of the SI?

Answer 22

Hydrolysis reactions in digestion
Facilitation of absorption (brings stuff close to the microvilli)
Facilitation of propulsion of gut contents
Combination of mucin granules to make mucus

Question 23

What are the sources of fluid in the small intestine?

Answer 23

Saliva
Oral intake 2L
Bile - IL
Gastric juice
Pancreatic juice - 1.5L
Intestinal juice - 1.5L

Take in 2L
Receive 6-7L from other places

Question 24

When is diarrhoea considered acute?

Answer 24

Less than 14 days

Question 25

What ion channel directly links to the cholera toxin? Exactly where is it located?

Answer 25

CFTR (Cystic Fibrosis Conductance Regulator)

Apical membrane of epithelial cells (enterocytes) lining the intestinal crypts of Lieberkuhn

Question 26

How does CFTR cause secretory diarrhoea?

Answer 26

Opening of the chloride channel
Chloride enters the lumen
Sodium follows paracellularly to balance the electrical gradient
Increase Socium Chloride creates an osmotic gradient driving more water into the gut lumen

Question 27

How does osmotic diarrhoea stop?

Answer 27

If you remove the offending agent

i.e. poo it out