Transport of Sodium and Chloride 1 and 2 Flashcards
How much of the sodium and chloride of the glomerular filtrate is reabsorbed in the proximal tubule?
55-65%
types of active transport in the neprhon
ATP-dependent
Co- and counter-transport
types of passive transport in the nephron
facillitated diffusion
channel-mediated diffusion
NA+/K+ ATPase
uses ATP to transport 3 Na+ out and 2 K+ into the cell
always located in the basolateral membrane
allows sodium to be the major energy currency of tubule cell transport
co- and counter-transport
transporters that couple favorable movement of sodium and/or potassium to move other ions and solutes
transcellular transport
solutes are taken up at the apical surface of the cell and traverse the cytoplasm and are excreted at the basolateral surface into the bloodstream
paracellular transport
ions/solutes flow between tubule cells
the driving force for paracellular flux comes from the lumenal vs. basolateral electrochemical gradient
extent depends on number and orcanization of tight junctions
What is the advantafe of a large paracellular flux?
mitigates against the formation of large electrical and chemical gradients
solvent drag
the process where bulk flow can carry ions and solutes against their graidents
occurs during massive water flux, particularly in the proximal tubule
paracellin-1
an Mg2+ channel located between cells of the thick asending limb and distal tubule
What are the reference points for membrane potentials?
outside the cell for transmembrane
interstitial for across lumen and interstitium
membrane potential in the presence of leaky tight junctions
the tubule cell behaves like an isolated cell
the voltage across each piece of membrane, apical or basal, is the same
transepithelial voltage = 0 mV
membrane potential in the presence of tight tight junctions
ionic conductances in the apical and basal membranes sum separately
basal K+ channels set voltage to -70 mV and apical Na+ channels set transmembrane voltage to +70 mV
transepithelial voltage = -140 mV
solute selectivity of the paracellular pathway
based on size
the cut-off can be in the 100s of mw
ion selectivity of the paracellular pathway
based on charge
resistance of the paracellular pathway
varies with the number of rows of junction proteins
increases along the tubule
What is the NaCl concentration in glomerular filtrate?
142 mM NaCl
What is the concentration of NaCl that the kidney excretes?
120 mM
What is the consequence of having leaky paracellular contacts in the proximal tubule?
the uptake becomes iso-osmotic
the solution that leaves the tubule has a similar ionic concentration to that entering the tubule
as a result, there is much less solution leaving and thus less total NaCl
proximal tubule sodium transcellular re-uptake mechanisms
apical cotransporters for glucose, amino acids, and other metabolites
apical Na+/H+ antiporter
basaolateral Na+/K+ ATPase
basolateral Na+/HCO3- transporter
proximal tubule sodium paracellular re-uptake mechanisms
osmotic gradient created by Na+ and HCO3= draws water from the lumen, carrying Na+ via solvent drag
proximal tubule transcellular Cl- re-uptake mechanisms
little or none in the first part of the proximal tubule, where Cl- in the lumen is increased from 115 to 135 mM
in the late proximal tubule, Cl- is unfavorably taken up at the apical surface through an electroneutral Cl-/anion counter-transporter
basolateral transport passively via an ion channel
basolateral transport coupled to a favorable K+ efflux
What are the possible anions in the late proximal tubule for chloride cotransport?
formate, OH-, HCO3-, and oxalate
proximal tubule paracellular Cl- re-uptake mechanisms
small amount occurs in the early proximal tubule via solvent drage promoted by the -3mV gradient across the tubule cell tight junctions
significant uptake in the late proximal tubule favored by an increased lumen to blood Cl- gradient
active mechanisms for changing or regulating the amount of re-uptake in the proximal tubule
feedback from vascular or renal transmitters play a neglifible role
passive mechanisms for changing the amount of re-uptake in the proximal tubule
glomerulotubular balance is a passive mechanism that maintains a constant fraction of Na+ and water re-uptake regardless of overall flow
the total amount of Na+ changes with tubular flow by the end of the prixmal tubule, but not the concentration
What happens to tight junctions starting with the tDLH?
they become tighter and reduces non-specific paracellular flow
function of the thick ascending limb
creates a dilute or concentrated urine
impermeable to water
concentration depends on presence of water channels in the collecting ducts
transcellular mechanisms of ion transport in the TAL
an apical Na+/K+/Cl- transporter
an apical Na+/H+ antiporter
basolateral Na+/K+ ATPase
What drugs inhibit the Na+/K+/Cl- cotransporter and what is the effect?
bumetanide and furosemide (loop diuretics)
dilutes medullary interstitium and increases amount of osmotically active Na+ in the collecting duct fluid
paracellular mechanisms of ion transport in the TAL
50% of Na+ leaves due to the +15 mV transcellular potential
no paracellular Cl- permeability
How is the positive potential created in the TAL?
relative impermeability of the tight junctions
K+ channel creates a -70 lumen vs intracellular potential
K+ and Cl- channel creates a -55mV intracellular vs. interstitial potential
result is a positive trans-epithelial potential
function of the DCT
further reduces tubule Na+ and Cl- concentrations to a minimum of 40 mM
mechanisms of ion transport in the DCT
transcellular is the major mechanism
Na+ and Cl- taken up at the apical surface by a co-transporter
driving force is the Na+ chemical gradient established by the basolateral Na+/K+ ATPase
basolateral chloride channel leads to Cl- efflux due to the negative potential
What drug inhibits the Na+/Cl- transporter in the DCT?
thiazide diuretics
function of the CCT and MCD
receives remaining 3% of NaCl
takes up Na+ to balance the sodium intake
mechanisms of ion transport in the CCT and MCD
principal cells move move sodium into the interstitum through EnaC sodium channels (voltage dependent
K+ channels on both membranes to prodice a -70 mV potential across the basolateral membrane and -30 mV across the apical membrane
paracellular Cl- uptake and Cl-/HCO3- exchanger in beta-interacalated cells
regulation of sodium uptake in the CCT and MCD
decreased renal perfusion stimulates release of renin from juxtaglomerular cells
this leads to the renin-angiotensin-aldosterone cascade that produces aldosterone
alodsterone up-regulates Na+ and K+ channels and aslo the ATPase in principal cells, increasing Na+ reuptake
loop diuretics
blocks the Na/K/Cl transporter in the TAL
indirectly leads to hypokalemia
increased concentration of Na+ flows into the collecting tubule, leading to increased Na+ entry via Na+ channels, which is balanced by K+ efflux
thiazide diuretics
blocks the Na/Cl transporter in the DCT
wekaer than loop diuretics because only 3-5% of Na+ absorption occurs in the DCT
promote Na+ loss, water loss, and hypokalemia
potassium-sparing diuretics
directly blocking principal cell Na+ channel in the CCT (amiloride, triamterine)
antagonizing aldosterone (spironolactone) - channel removal
small effect on Na+ absorption, does not result in increased Na+ influx, so K+ release is not increased
