lecture 25 - chloride secretion Flashcards
NaK2Cl symporter transports? (where is it found)
1 Na+, 1 K+ and 2 Cl- into the cell from the basolateral membrane.
once they have entered into the cell, through the NaK2Cl symporter, what is the fate of the Na+, K+ and Cl- ?
- Na+ pumped out via basolateral Na pump - K+ exits via channel in the basolateral membrane - Cl- leaves via passive diffusion through CFTR ion channel
transcellular transport of Cl- across the epithelium induces?
Na+ and water fluxes
in chloride secretion, how does the permeability of tight junctions differ to that of glucose absorption?
in chloride secretion they are more permeable to Na+, whereas they are more permeable to Cl- in glucose absorption.
what is the rate limiting step of Cl- secretion
Cl- leaving the cell through CFTR ion channel. Cl- is accumulated well above its electrochemical gradient but opening of this channel is strictly regulated and Cl- can’t leave any other way.
chemical that initiates Cl- secretion
secretogogues
CFTR stands for… does everyone have it or nah?
Cystic Fibrosis transmembrane conductance regulator. Cl- ion channel. yeah g, everyone has it
CFTR overstimulation leads to
diarrhoea
CFTR dysfunction =
cystic fibrosis
secretory diarrhoea is associated with secretory cells in the _____ of the ____ ______ and ______.
secretory diarrhoea is associated with secretory cells in the _crypts_ of the _small_ _intestine_ and _colon_.
secretory diarrhoea less common cause =
higher than normal concentrations of endogenous secretogogues produced by tumours or inflammation
More common cause of secretory diarrhoea =
ENTEROTOXINS secreted by CHOLERA and other bacteria cause an overstimulation of CFTR
_______ (ligand) binds and activates the _ ______ which moves along the ________ membrane to activate the ______ ______. This enzyme can then convert ATP to ____, which goes on to activate _____ _____ _, in turn phosphorylating _____ (found in the _____ membrane) - the channel is now open. Once the ligand unbinds the gate _____.
_secretogogues_ (ligand) bind and activate the _G_ _protein_ which moves along the _basolateral_ membrane to activate the _adenylate_ _cyclase_. This enzyme can then convert ATP to _cAMP_, which goes on to activate _protein_ _kinase_ _A_, in turn phosphorylating _CFTR_ (found in the _apical_ membrane) - the channel is now open. Once the ligand unbinds the gate _closes_.
how does Cholera affect the control over opening/closing of CFTR gate?
IRREVERSIBLY activates adenylate cyclase which will keep CFTR open.
how will Cholera kill you?
Cl- continuously accumulates in the lumen, therefore there is extreme water loss - up to 20Kg
treatment for over-secretion
“oral rehydration therapy” - counter-acted glucose/Na stimulated water flux.
How do you cop Cystic fibrosis?
inherited from two heterozygous parents
cystic fibrosis most prevalent in?
Northern Europe. Children and young adults are most affected.
mean survival with cystic fibrosis?
38 years
which tissues does cystic fibrosis largely affect
epithelial
CF symptoms in liver
function disrupted and plugs bile ducts
CF symptoms in pancreas
ducts block, so digestive enzymes cannot be delivered
CF symptoms in small intestine
thick stool - constipation
CF symptoms reproductive tract
infertile males - sperm production, but not enough ejaculate. Mucus in females may block sperm from egg.
treatment of CF
- chest percussion - antibiotics for infection - Pancreatic enzyme replacement - attention to nutritional status
Healthy sweat production
- primary secretion of isotonic fluid by acinar cells 2. secondary reabsorption of NaCl, producing a hypotonic solution
sweat production in cystic fibrosis patients
initial isotonic secretion by acinar cells, however, epithelial cells in sweat glands fail to reabsorb NaCl = salty sweat.
is CFTR an ion channel or a pump?
ion channel i.e. water filled pore
movement of Cl- through pore is regulated by which 3 cytoplasmic domains?
2 Nucleotide binding domains and 1 regulatory domain
what must occur before the channel can open. How does it close again
- The regulatory (R) domain must first be phosphorylated (regulated by protein kinase A) 2. ATP binds to each nucleotide binding domain = gate OPEN 3. gate closes when ATP is hydrolysed
in a healthy brother, how is the lung surface kept moist
balance between Cl- secretion and Na+ absorption
lung surface in CF patient
- dry (no isotonic secretion) - thick and sticky mucus secreted - cilia can’t sweep - WBCs build up in mucus - break down lung tissue = less surface area for gas exchange. - most deaths in CF result from this
