Water Balance in the GI Tract Flashcards
What does faeces normally contain?
100ml of water along with 50ml cellulose, bilirubin and bacteria.
What is intestinal fluid movement always coupled to?
Solute movement.
What 2 routes may water move through?
Transcellular or paracellular routes.
Name the 5 principle mechanisms of sodium transport.
- Na+/glucose co-transport.
- Na+/amino acid co-transport.
- Na+/H+ exchange.
- Parallel Na+/H+ and Cl-/HCO3- exchange.
- Epithelial Na+ channels (ENaC).
What is the most important sodium transport in the post-prandial phase?
Na+/glucose co-transport and Na+/amino acid co-transport.
Where does sodium/glucose/amino acid co-transport occur?
Throughout the small intestine.
Where does Na+/H+ exchange occur?
In the duodenum and jejunum.
What is Na+/H+ exchange stimulated by?
Luminal bicarbonate.
What pumps sodium from the enterocyte into the interstitial fluid?
Na+/K+ATPase.
Where does parallel Na+/H+ and Cl-/HCO3- exchange occur?
In the ileum and colon.
When is parallel Na+/H+ and Cl-/HCO3- exchange most important?
In the interdigestive period.
Where are epithelial Na+ channels and what are they regulated by?
The colon (particularly distal), regulated by aldosterone.
What type of transport is Na+/glucose and Na+/amino acid co-transport?
Secondary active transport.
What does it mean when it is said that Na+/glucose and Na+/amino acid co-transport and the Na+/K+ATPase are electrogenic?
It creates an electrical gradient.
What does the electrical gradient produced by Na+/glucose and Na+/amino acid co-transport and the Na+/K+ATPase cause?
The lumen to be negative which drives the parallel absorption of Cl-.
Is Na+/glucose and Na+/amino acid co-transport regulated?
No.
What transporters are at the apical and basolateral membranes of enterocytes in Na+/H+ exchange?
Basolateral - NHE1. Apical - NHE2, NHE3.
What is the function of the NHE1 transporter?
It regulates cytoplasmic pH (is present in most cells).
What stimulates Na+/H+ exchange at the apical membrane in the jejunum?
The alkaline environment of the lumen due to presence of bicarbonate from the pancreas.
Is Na+/H+ exchange electroneutral?
Yes.
In Na+/H+ and CI-/HCO3- exchange in parallel, what is pumped into and out of the cell?
In: sodium and chloride.
Out: hydrogen and bicarbonate.
Is Na+/H+ and CI-/HCO3- exchange in parallel electroneutral?
Yes.
What regulates Is Na+/H+ and CI-/HCO3- exchange in parallel and how?
Intracellular cAMP, cGMP and calcium - all reduce NaCl absorption.
How does E.coli cause diarrhoea?
It releases a heat stable enterotoxin which activates adenylyl cyclase and increases intracellular cAMP.
What are epithelial sodium channels mediated by?
Increased by aldosterone, not regulated by cAMP or cGMP.
What are the functions aldosterone has involving ENaC?
- Opens ENaC (seconds).
- Inserts more ENaC into membrane from intracellular vesicle pool (minutes).
- Increases synthesis of ENaC and sodium potassium pump (hours).
Is ENaC electroneutral?
No, electrogenic.
What are the 2 routes that chloride can be absorbed in?
Transcellular or paracellular.
In the small intestine what provides the driving force of chloride absorption?
Electrogenic transport of Na+ through Na+/glucose and Na+/amino acid co-transport.
In the large intestine what provides the driving force of chloride absorption?
Electrogenic movement of Na+ through ENaC.
What are the other mechanisms of absorption of chloride?
Cl-/HCO3- exchange (ileum, proximal and distal colon), parallel Na+/H+ and Cl-/HCO3- exchange (ileum and proximal colon).
What usually occurs more, chloride absorption of chloride secretion?
Absorption.
What type of cells is chloride secreted from?
Crypt cells.
What 3 processes involved on the basolateral membrane cause an increase in intracellular chloride?
Na+/K+ATPase, Na+/K+/2Cl- co-transporter, K+ channels (IK1 and BK).
What drives the Na+/K+/2Cl- transporter?
Low intracellular sodium (produced by Na+/K+ATPase).
How does K+ then leave the cell?
Through K+ channels.
What causes Chloride to move across the apical membrane and through which transporter?
Increased concentration of intracellular chloride (produced an electrochemical gradient). CFTR.
How does sodium then get secreted into the lumen?
Lumen negative potential develops, so sodium is secreted through paracellular pathway.
What causes stimulation of the CFTR channel?
Calcium and cAMP.
Why is there normally little or no secretion of chloride?
Apical CFTR is either closer or not present.
What causes secretion of chloride to occur?
Bacterial endotoxins (cholera toxin, heat stable enterotoxin, c.diff), hormones and neurotransmitters (e.g. VIP, guanylin, ACh, bradykinin, 5-HT), immune cell products (prostaglandins, histamine), some laxatives e.g. bile acids.
How does activation of CFTR occur?
Indirectly as a result of generation of second messengers e.g. cAMP (cholera, VIP, histamine), cGMP (heat stable enterotoxin, guanylin), Ca2+ (ACh, bradykinin, 5-HT).
What 2 mechanisms allow increased conductance of chloride?
Opening of CFTR, insertion of CFTR from intracellular vesicles into the membrane.
What type of diarrhoea is produced from increased chloride secretion?
Secretory diarrhoea.
What are the possible complications of diarrhoea?
Dehydration, metabolic acidosis and hypokalaemia.
What are the 4 main mechanisms of diarrhoea?
Impaired absorption of NaCl, excessive secretion, non-absorbable/poorly absorbable solutes in intestinal lumen (e.g. lactase deficiency), hypermotility.
What transport mechanism does rehydration therapy exploit?
SGLT1 (contains glucose so allows more absorption of sodium).
What are the actions of opioids on the alimentary tract?
Inhibition of enteric neurones, decreased peristalsis, increased segmentation, increased fluid absorption, constriction of pyloric and ileocaecal and anal sphincters, increased tone of large intestine.
What are the major opioid agonists used in diarrhoea?
Codeine (only really used if analgesic action needed as well), diphenoxylate and loperamide (last 2 have low CNS peneration and low solubility in water.
What anti-diarrhoeal inhibits enkephalinase to raise endogenous enkephalin levels?
Racecadotril (prodrug of thiorphan), not licensed in Scotland.
