Renal Handling of Sodium Flashcards
1
Q
what is glomerulartubular balance?
A
- glomerulotubular balance refers to constant fractional reabsorption of Na+ in the proximal tubule
- the PT consistently reabsorbs 65% of the Na+ that is filtered in bowman’s capsules
- even if GFR increases, which will increase the filtered load (filtered load = GFRxPna), the portion of Na+ reasorbed from that filtered load stays constant
- = “load dependence”
- even if GFR increases, which will increase the filtered load (filtered load = GFRxPna), the portion of Na+ reasorbed from that filtered load stays constant
- the PT consistently reabsorbs 65% of the Na+ that is filtered in bowman’s capsules
2
Q
other than the proximal tubule, where is Na+ reabsorbed?
how much Na+ is reabsorbed at this segments?
what factors regulate Na+ reabsorption at these segments?
A
these reabsorption fractions are highly variable and all dependent on volume status and intrarenal flow
-
loop of henle: reabsorbs 20% of filtered load of Na+. depends on
- volume status & flow
-
distal tubule: reabsorbs 5-10% o the filtered load of Na+. depdends on
- volume status & flow
-
collecting tubules: reabsorb about 5% of the filtered load of Na+. dependent on
- volume status & flow
- in addition Na+ reabsorption tightly controlled by aldosterone
these reabsorption fractions are highly variable are the dependent on volume status.
3
Q
- what is the normal f_ractional excretion_ and fractional reabsorption and Na?
- how are these values related to dietary intake?
A
- across the nephron, we reabsorb 99.4% of filtered sodium (GFR x Pna)
- so, FA = 99.4%
- and FE = 0.6%
- based on our filtered load, this is about 150 mEq of sodium excreted per day.
- at steady state, our urinary excretion = urinary intake
- we excrete the amount of Na+ we consumed our diet that day
4
Q
what is the importance of Na+ presence in the filtrate?
what transporter facilitates its role?
A
- Na is the most abundant solute in the filtrate
- its reabsorption is coupled to reabsorption of almost all other solutes
- thus, a reducation in Na+ raebsorption decreases reabsorption of almost all other solutes
- reabsoprtion of Na+ occurs down a Na+ concentration gradient established by the Na/K ATPase
- about 90% of total renal enegy is dedicated to operatio fo the Na/K ATPase
5
Q
describe the ratio of Na:K in the proximal tubular lumen, cell, and ajacent peritubular capillary.
- why is this?
- what does it drive?
A
- the Na:K ratio in the tubular lumen and peritubular capillary is nearly the same ([145]/[4]) in each compartment
- this is because of the leaky tight junctions (paracellular junctions) that allows passive Na+ diffusion from tubular lumen into peritubular capillary until equilibration
- the Na/K ATPase on the basolateral membrane actively pumps Na+ out of PT cell and K+ into the cell.
- this creates a low N:K+ ratio in the cell such that Na+ wants to diffuse both from the tubule into the cell
6
Q
- discuss the prevalence of Cl- in the solute
- discuss the movement of Cl- throughout the proximal tubule
A
- Cl- is tee most abundant anion in the glomerular filtrate
- overall, it is the major anion that follows Na+ to maintain electric neutrality
- in the proximal tubule:
-
early proximal tubule: preferential reabsorption of HCO3, HCPO4- (coupled to Na+ reabsoprtion) limits the reabsorption of Cl- due to the negative intracellular charge they create
- Cl- reabsoprtion doesn’t keep up with Na+/water reabsorption, so the concentration of [Cl-] in the tubule actually increases
- late distal tubule: [Cl-] in the tubule has increased to the point where Cl- reabsorption is favorable. Cl-, electrochemically acompanied by Na+ diffuses into the cell (Cl- driven Na+ reabsorption)
-
early proximal tubule: preferential reabsorption of HCO3, HCPO4- (coupled to Na+ reabsoprtion) limits the reabsorption of Cl- due to the negative intracellular charge they create
7
Q
outline overall reabsorption in the proximal tubule (ions, channels, ect)
A
- Na/K ATPase on basolateral membrane actively extrudes Na+ into the lumen cell
- this creates an Na+ gradient into the cell, which:
- sets up the following secondary active transport:
-
Na+/H+ antiport
- H+ secreted in exchange for Na+
- this secreted H+ facilitates:
- reabsorption of HCO3-
* heavily reabsorbed in early PT
* relies on carbonic anhydrase
- reabsorption of HCO3-
- reabsorption of Cl
* via “parallel operation” of Na/H antiport with Cl-/OH and Cl-/formate exchangers
- reabsorption of Cl
-
various symports:
- Na+/phophate –> phosphate reabsorbed
- heavily reabsorbed in proximal tubule
- Na+/glucose –> glucose reabsorbed
- Na+/amino acids –> amino acids reabsorbed
- Na+/phophate –> phosphate reabsorbed
-
Na+/H+ antiport
- sets up the following secondary active transport:
- this creates an Na+ gradient into the cell, which:
8
Q
dsicuss the role of Na/H antiporter in the proximal tubule
A
roles:
I. Na/H antiporter secretes H+ against its gradient:
- pH of tubular filtrate is acidic
- H+ in tubule is accepted by proton acceptors (bases) - HCO3, HPO4, facilitating their reabsorption
II. Na/H antiporter operates “parallel” to Cl-/base exchangers, coupling Cl- reabsorption to Na+ reabsorption”
- Cl-OH- exchanger:
- H+ secretion induces secretion of OH- (a base)
- OH- secretion promotes Cl- reabsorption (charge neutralization)
- Cl-formate exchanter
- H+ secetion induces secretion of formate (a base)
- formate secretion promtoes Cl- reabsorption (charge neutraliation)
9
Q
discuss the activity of the Na/H+ antiporter in a hypovolemic state
A
Na/H+ antiporter activity increased by sympathetics and angiotensin II in a hyopvolemic state
this encourages Na+ reabsorption
10
Q
describe the role of Cl- driven Na+ absorption in the proximal tubule and how it occurs
A
- permitted by preferential co-transport of other anions (HCO3-, HPO4-) with Na+ in the early tubule
- the increased [Cl-] in the late tubular lumen permits electrogenic Na+-Cl-, which accounts for 30% of total Na+ reabsorption seen in this segment of the PT
11
Q
discuss the tubular:plasma ratios ratio of key solutes throughout the proximal tubules
A
- Na+ reabsorption is isotonic, so its concentration remains even throughout PT
- HCO3/HPO4, amino acids and glucose heavily reabsorbed in the early PT
- urea and Cl- concentrations throughout PT then increased due to isotonic Na+ movement then are ultimately reabsorbed “generation of favorable gradients”
12
Q
thin desending loop of henle
- discuss its permeability
- discuss solute/water movement
A
- permeability:
- impermeable to solute
- permeable to water
- due to high presence of aquaporins
- here
- water reabsorbed from tubule as it moves through increasing interstitial osmolarities in the hypertonic medulla
- solutes in tubule (mainly Na and Cl) are significantly concentrated (4-5)
13
Q
what is the max concentration filtrate in thin ascending limb can reach?
A
tubular filtrate can get concentrated up to 1200 in inner medulla
14
Q
thin ascending loop of henle
- dicuss permeability of this segment
- discuss solute/fluid movement across this segment
A
- permeability
- impemeable to water
- permeable to solutes
- Na, Cl- (freely diffuse) and urea (utilized a transporter)
- thin ascending limb moves up through a progressively hypotonic interstitium
- NaCl reabsorbed: the Na+ and Cl- rapidly move of the concentrated filtrate, and the filtrate becomes progressively more dilute
-
urea seceted:
- though the filtrate is hypertonic, that hypertonicity is almost due to remaining Na & Cl- (most solutes were entirely reabsorbed in the PCT)
- as Na & and Cl- move down their concentration gradients into the blood, the filtrate becomes dilute (because water cant follow) , and the tubular [urea} drops
- this favors urea secretion
15
Q
thick ascending loop of henle (TAL)
- discuss permeability in this segment
- discuss solute movement & important channels
A
- permeability
- impermeable to water (like thin ascending limb)
- permeable to solutes
- filtrate in TAL still hypertonic to interstitium as it moves through outer medulla
- Na/K ATPase on basolateral membrane sets up Na+ gradient into cell
-
NKCC2 channel on tubular membrane:
-
brings of Na, K, 2 C into from tubule into cell
- (K+ and Cl- moving against their concentration gradient)
- K+ then leaks back into filtrate
-
brings of Na, K, 2 C into from tubule into cell
- back leak of K+ creates a positive lumen potential that encourages reabsorption of cations Na+, Ca++, and Mg via the paracellular route
18
Q
what are the means by which Na+ is reabsorbed in the TAL?
A
- NCCK
- Paracellular diffusion
- Na+/H+ antiporter
20
Q
summary of ion/fluid movement in the loop of henle
A
- thin descending: water reabsorbed
- thin ascending: NaCl reabsorbed, urea secreted
- thick ascending: Na, Cl, Mg, Ca+ reabsorbed
21
Q
distal tubule
- discuss permeability in this segment
- discuss solute/fluid movement in this segment
A
- permeability: like the thin/thick ascending limb, the distal tubule is
- impermeable to water
- permeable to solutes
- solutes:
-
NCC:
- Na+ and Cl- reabsorption
- this dilutes tubular fluid
- Ca++ reabsorption
-
NCC:
24
Q
cortical collecting tubule
- discuss permeability, solute movement, and transporters in this segment
A
-
principle cells: almost all solute movement occurs through the principle cells of the collecting ducts
- Na/K ATPase sets up Na+ gradient
- ENaC channels: permit Na+ reabsorption and K+ secretion
- water follows Na+ (isotonic Na= reabsorption)
-
rapid entry of Na+ into cell along gradient produces a negative lumen potential that:
- pulls Cl- into cell
- drives K+ out of cell
-
intercalated cells:
-
__secrete H+ in response to - lumen potential generated by adjacent priniciple cells
- H+ secreted in the form of ammonium (NH4)
-
__secrete H+ in response to - lumen potential generated by adjacent priniciple cells
overall: NaCl reabsorbed, H+ and K+ secreted
