Water and balance in the GI tract Flashcards
How is water absorbed in the GI tract?
It is a passive process driven by the transport of solutes (particularly Na+) from the lumen of the intestine to the bloodstrea
How many water enters and is absorbed by the GI tract every day?
9.3 liters enter the tract
8.3 litres are absorbed by the small intestie
1 litre enters large intestine of which 90% is absrobed
What makes up faeces?
100ml water
50ml cellulose, billirubin and bacteria
What is diarrhoea defined as?
Loss of lfuid and solutes from the GI tract in excess of 500ml per day
What transporters are present throughout the small intestine?
Na+/glucose co-transport
Na+/ amino acid co-transport
What transporters are presentin the duodenum and jejunum?
Na+/ H+ exchange
Stimulated by luminal HCO3-
What transporters are present in the ileum and colon?
Parallel Na+/H+ and Cl-/HCO3- exchange
What transporters are present in the colon?
Epithelial Na+ channels
Regualted by aldosterone
What are the major mechanisms of postprandial Na+ in the jejunum?
Na+/glucose
Na+/ amino acid cotransporter
What type of transport are the major co-transporters of postprandial Na+ absorption?
Seconadry active transport and are electrogenic, as is the Na+/K+ ATPase, the overall tranport of Na+ geneerates a transepithelial potential in which the lumen in negative - driving parallel absorption of Cl-
What stimulates echange at the apical membrane of the jejunum (Na+/H+ exchnage) ?
Stimualted by the alkaline environemnt of the lumen (high pH = low proton conc) ue to the presence of bicarbonate from the pancreas
What is the priamry mechanism of Na+ absorption in the interdigestie period?
Na+/H+ and Cl-/HCPO3- parallel exchange
How are the Na+/H+ and Cl-/HCO3- exchangers regulated?
Intraellular cAMP, cGMP and Ca2+ all reducing NaCl absorption
What does a reduction in NaCl absorption cause?
Diarrhoea (secretory diarrhoea due to infection with E.coli - heat stable enterotoxin from which activated adenylate cyclase and increases intracellular cAMP)
What do epithelial Na+ channels mediate?
Electogenic Na+ absorption in the distal colon, highly efficient and important in Na+ conservation
Increased by aldosterone
What are the actions of aldosterone?
Opens ENaC
Inserts more ENaC into membrane from intracellular vesicle pool
Increases synthesis of ENaC and Na+/K+ ATPase
What are the cellular mechanisms of Cl- absorption?
Can occur passively via transcellular or paracellular routes
Driving force in the small intestine is provided by lumen negative potential due to electrogenic transport of Na+
Large intestine driving forve provided by negative potential due to electrogeenic movement of Na+ thorugh ENaC
Where is Cl- secreted from?
Crypt cells rather than villus cells, important in many diarrhoeas
When is the CFTR activated?
Bacterial entereotoxins (cholera toxin, enterotoxin, c diff toxin)
Hormones and neurotransmitters (VIP, guanylin, ACh, bradykinin, 5-HT)
Immune cells products (prostaglandins, histamine)
Laxatives (bile acids)
What secondary messengers can activated CFTR?
cAMP (cholera toxin, VIP, histamine)
cGMP (enterotoxin, guanlylin)
Ca2+ (ACh, bradykinin, 5-HT)
What does Cl- conductance mediated by CFTR result in?
Opening of channels at the apical membrane
Insertion of channels from intracellular vesicale sinto the membrane
Secretory diarrhoea
What can cause diarrhoea?
Infectious agents - viruses, bacteria Chronic disease Toxins Drugs Psychological factors
What can diarrhoea result in?
Can involve small or large intestine
Result in dehydration (Na+ and h2o loss), metabolic acidosis, hypolakaemia
How can severe diarrhoea be treated?
Maintenance of fluid and electrolye balance
Use of anti-infective agents
Use of non-antimicrobial antidiarrhoeal agents
How does cholera cause diarrhoea?
Cholera toxin enters enterocyte Enxymatically inhibits GTPase Increases activity of adenylate cyclase Increases the conc of caMP caMP stimualtes CFR Hypersectrion of Cl- with Na+ and water following
What congenitcal defects can lead to diarrhoea?
Congenital chloridorrhoea - absence of Cl=/HCO3- exchanger)
How does rehydration therapy work?
2Na+ bind
Affinity for glucose increases, glucose binds
Na+ and gluocse translocate from extracellular to intracellular
2 Na+ dissociate, affinity for glucose falls
Glucose dissociates
Cycle is repeated
What do oral rehydration salts contain?
Gluocse NaCl Sodium bicarbonate Potassium chloride Absoprtion of sodium and glucose by SGLT1 causes the accompanying absorpton of water
What are the actions of opioids on the alimentary tract?
Inhibition of enteric neurones (hyperpolarization via activation of opioid receptors)
Decreased peristalsis , increased segmentation
Increased fluid absorption
Constriction of pyloric, ileocaecal and anal sphincters
Increased tone of large intestine
What are major opioid agonists used in diarrhoea?
Coedine
Diphenoxylate
Loperamide
