Transport of Sodium and Chloride 1 and 2

Question 1

How much of the sodium and chloride of the glomerular filtrate is reabsorbed in the proximal tubule?

Answer 1

55-65%

Question 2

types of active transport in the neprhon

Answer 2

ATP-dependent

Co- and counter-transport

Question 3

types of passive transport in the nephron

Answer 3

facillitated diffusion

channel-mediated diffusion

Question 4

NA+/K+ ATPase

Answer 4

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

Question 5

co- and counter-transport

Answer 5

transporters that couple favorable movement of sodium and/or potassium to move other ions and solutes

Question 6

transcellular transport

Answer 6

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

Question 7

paracellular transport

Answer 7

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

Question 8

What is the advantafe of a large paracellular flux?

Answer 8

mitigates against the formation of large electrical and chemical gradients

Question 9

solvent drag

Answer 9

the process where bulk flow can carry ions and solutes against their graidents

occurs during massive water flux, particularly in the proximal tubule

Question 10

paracellin-1

Answer 10

an Mg2+ channel located between cells of the thick asending limb and distal tubule

Question 11

What are the reference points for membrane potentials?

Answer 11

outside the cell for transmembrane

interstitial for across lumen and interstitium

Question 12

membrane potential in the presence of leaky tight junctions

Answer 12

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

Question 13

membrane potential in the presence of tight tight junctions

Answer 13

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

Question 14

solute selectivity of the paracellular pathway

Answer 14

based on size

the cut-off can be in the 100s of mw

Question 15

ion selectivity of the paracellular pathway

Answer 15

based on charge

Question 16

resistance of the paracellular pathway

Answer 16

varies with the number of rows of junction proteins

increases along the tubule

Question 17

What is the NaCl concentration in glomerular filtrate?

Answer 17

142 mM NaCl

Question 18

What is the concentration of NaCl that the kidney excretes?

Answer 18

120 mM

Question 19

What is the consequence of having leaky paracellular contacts in the proximal tubule?

Answer 19

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

Question 20

proximal tubule sodium transcellular re-uptake mechanisms

Answer 20

apical cotransporters for glucose, amino acids, and other metabolites

apical Na+/H+ antiporter

basaolateral Na+/K+ ATPase

basolateral Na+/HCO3- transporter

Question 21

proximal tubule sodium paracellular re-uptake mechanisms

Answer 21

osmotic gradient created by Na+ and HCO3= draws water from the lumen, carrying Na+ via solvent drag

Question 22

proximal tubule transcellular Cl- re-uptake mechanisms

Answer 22

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

Question 23

What are the possible anions in the late proximal tubule for chloride cotransport?

Answer 23

formate, OH-, HCO3-, and oxalate

Question 24

proximal tubule paracellular Cl- re-uptake mechanisms

Answer 24

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

Question 25

active mechanisms for changing or regulating the amount of re-uptake in the proximal tubule

Answer 25

feedback from vascular or renal transmitters play a neglifible role

Question 26

passive mechanisms for changing the amount of re-uptake in the proximal tubule

Answer 26

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

Question 27

What happens to tight junctions starting with the tDLH?

Answer 27

they become tighter and reduces non-specific paracellular flow

Question 28

function of the thick ascending limb

Answer 28

creates a dilute or concentrated urine impermeable to water concentration depends on presence of water channels in the collecting ducts

Question 29

transcellular mechanisms of ion transport in the TAL

Answer 29

an apical Na+/K+/Cl- transporter an apical Na+/H+ antiporter basolateral Na+/K+ ATPase

Question 30

What drugs inhibit the Na+/K+/Cl- cotransporter and what is the effect?

Answer 30

bumetanide and furosemide (loop diuretics) dilutes medullary interstitium and increases amount of osmotically active Na+ in the collecting duct fluid

Question 31

paracellular mechanisms of ion transport in the TAL

Answer 31

50% of Na+ leaves due to the +15 mV transcellular potential no paracellular Cl- permeability

Question 32

How is the positive potential created in the TAL?

Answer 32

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

Question 33

function of the DCT

Answer 33

further reduces tubule Na+ and Cl- concentrations to a minimum of 40 mM

Question 34

mechanisms of ion transport in the DCT

Answer 34

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

Question 35

What drug inhibits the Na+/Cl- transporter in the DCT?

Answer 35

thiazide diuretics

Question 36

function of the CCT and MCD

Answer 36

receives remaining 3% of NaCl takes up Na+ to balance the sodium intake

Question 37

mechanisms of ion transport in the CCT and MCD

Answer 37

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

Question 38

regulation of sodium uptake in the CCT and MCD

Answer 38

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

Question 39

loop diuretics

Answer 39

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

Question 40

thiazide diuretics

Answer 40

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

Question 41

potassium-sparing diuretics

Answer 41

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