MET 2 - A Gut Feeling Flashcards
What happens if you lose too much bicarbonate in the gut?
Metabolic acidosis
What does ORT do for diarrhoea, why is it effective?
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
What symptoms does low K+ cause?
Muscle cramping and weakness
Arrhythmias
What are treatments of cholera except ORT?
Antimotility agents
Antibiotics
Treat underlying cause of diarrhoea
Oral vaccines
Explain the absorption of water, ions and solutes in the small intestine
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)
Define diarrhoea.
Frequent bowel evacuation with passage of abnormally soft or liquid faeces (1/2)
Daily passage of more than 250 grams faeces (1/2)
Give four processes that require the presence of water in the lumen of the small intestine
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
What is the ion channel indirectly activated by cholera toxin? Exactly where is this channel located?
2 marks
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).
Detailing (i) the cellular mechanism and (ii) the underlying forces at play: Explain how activation of the CFTR channel causes secretory diarrhoea.
(3 marks)
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).
Which route does sodium take when it enters the lumen? Using your knowledge of body fluid compartments explain why.
2 marks
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).
What is the mechanism of action of cholera?
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
What causes osmotic diarrhoea?
Laxatives
Malabsorption (e.g. coelic disease)
Food intolerance (e.g. lactose staying in the lumen because no lactase)
What causes secretory diarrhoea?
Cholera infection
Enterotoxigenic E coli (traveller’s diarrhoea)
Bile acid malabsorption
Define: diarrhoea
Frequent bowel evacuation of abnormally soft and liquid faeces
Daily passage of more than 250g
3x a day of loose stools
What happens to the fluid that enters the Small Intestine?
80% of the liquid is absorbed by the time you get to the large intestine
Tight relationship between water and solute absorption
What route does Na+ take when entering the lumen? Using your knowledge of body compartments to explain why?
Sodium travels paracellularly and comes from the interstitial fluid
Sodium does not come from the enterocytes because body cells contain very little sodium
Define osmotic diarrhoea
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
Define: secretory diarrhoea
Excessive secretion of electrolyte and water into the lumen due to inhibition or overactivaion of the enzymes in the enterocytes
What is inflammatory diarrhoea?
Inflammation leading to the destruction of enterocytes
Direct loss of fluid and blood and reduced absorption of water
What causes inflammatory diarrhoea?
IBD (Crohns, ulcerative collitis)
Campylobacteriosis, salmovellosis
Viral gastroenteritis
What type of bacteria causes chloera? What is its name?
Vibrio cholerae
Grame negative
What four process require water in the lumen of the SI?
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
What are the sources of fluid in the small intestine?
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
When is diarrhoea considered acute?
Less than 14 days
What ion channel directly links to the cholera toxin? Exactly where is it located?
CFTR (Cystic Fibrosis Conductance Regulator)
Apical membrane of epithelial cells (enterocytes) lining the intestinal crypts of Lieberkuhn
How does CFTR cause secretory diarrhoea?
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
How does osmotic diarrhoea stop?
If you remove the offending agent
i.e. poo it out
