Function of Epithelia Flashcards
What is tight control of the airway surface liquid essential for?
Pathogen defence
Mucus clearance by cilia
Paracrine Hormone Signalling
O2 uptake and CO2 exchange
What is the genetic defect in CF?
loss of phenylalanine at 508 causes defect in CFTR Cl channel
What does the CFTR mutation cause?
mucus accumulation and bacterial colonisation in the lung
digestive and reproductive problems due to defective Cl transport
How are electrolytes balanced in the kidney?
nutrient reabsorption from filtrate
fluid reabsorption from filtrate
electrolyte balance
What is PHA caused by?
loss of function mutations on ENaC subunits
What is PHA?
heriditary disease associated with resistance to aldosterone leading to increase Na excretion in urine, dehydration, hypotension, hyperkalaemia and metabolic acidosis
What is aldosterone?
adrenal mineralocorticoid hormones which regulates renal Na retention and K secretion
Where is PHA most evident?
kidney, sweat gland, pancreatic and salivary gland function and can be lethal due to excessive hypotension and circulatory collapse
What is the most lethal form of PHA?
loss of function mutations in the a,b and y ENaC which are distribute throughout the length of the protein
How much fluid is secreted and reabsorbed in the gut daily?
9L input into the system - saliva, gastric juice etc
8.9l reabsorbed through sm.intestine and large intestine
What signalling pathway does cholera toxin stimulate?
stimulates overproduction of cAMP from AC-> PKA
What is the result of PKA overactivation in cholera?
PKA stimulates NKCC channel and CFTR channel
Cl brought from blood to cell by NKCC
Cl removed to gut lumen by CFTR
Cl pulls water into the lumen and causes diarhhoea and dehydration
What are the typical IC and EC ion concentrations of K+?
IC 155
ECF 5
What are the typical IC and EC ion concentrations of Na+?
ICF - 12
ECF 145
What are the typical IC and EC ion concentrations of Mg?
ICF - 15
ECF -2
What are the typical IC and EC ion concentrations of Ca?
ICF -2
ECF-2
What are the typical IC and EC ion concentrations of Cl?
ICF - 4
ECF - 110
What is the Fick principle and what does it describe?
J = P.deltaC
describes the ionic flux outside the cell
How is flux over the cell membrane described?
J = G.E
When is the net flux of K over the membrane 0?
when Gk.Ek=Pk.Ck
Give the Nernst Equation
Em = RT/zF . ln [Kout]/[Kin]
What is the membrane potential where there will be no net movement of K+ at 37C?
-40mV
What are the Em for Na, K, and Cl?
K = -40mV Na = +66.5mV Cl = -88.4mV
Why is Na+ maintained so low inside the cell?
Na-pump maintains iso-osmotic conditions as water will follow Na into the cell
How does the b-adrenoceptor cause water movement across the paracellular membrane?
activated by epinephrine -> AC-> cAMP-> PKA-> NKCC -> IC cl- increase-> cell hyperpolarises -> Cl channel opens -> Cl out to lumen -> water pulled across
How can you increase ENaC expression?
glucocorticoids, mineralocorticoids, O2
What factors increase voltage in the ussing chamber?
increased abundance of channels or pump activity
What factors increase current in the ussing chamber?
channels and tight junctions opening
What factors increase resistance in the ussing chamber?
channel/tight junction closure, small cell, low abundance of channels/transporters
What does an Ussing chamber allow?
Analysis of apical and basolateral membrane currents by use of agonists, use of channel or pump blockers, gene KO and ionic species permeability
