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S2B5 Physiology > Renal Handling of Sodium > Flashcards

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”
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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.

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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
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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
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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
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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)
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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:
              1. reabsorption of HCO3-
                * heavily reabsorbed in early PT
                * relies on carbonic anhydrase
              1. reabsorption of Cl
                * via “parallel operation” of Na/H antiport with Cl-/OH and Cl-/formate exchangers
        • various symports:
          • Na+/phophate –> phosphate reabsorbed
            • heavily reabsorbed in proximal tubule
          • Na+/glucose –> glucose reabsorbed
          • Na+/amino acids –> amino acids reabsorbed
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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)
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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

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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
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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”
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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)
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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

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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
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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
    • back leak of K+ creates a positive lumen potential that encourages reabsorption of cations Na+, Ca++, and Mg via the paracellular route
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16
Q

overall, what solutes are reabsorbed at the TAL?

A
  • Na+, Cl-, Ca++, Mg++
17
Q

how does the tonicity of the tubular fluid change throughout the ascending limb?

A

it becomes more dilute

18
Q

what are the means by which Na+ is reabsorbed in the TAL?

A
  • NCCK
  • Paracellular diffusion
  • Na+/H+ antiporter
19
Q

discuss the endogenous regulators of NKCC pump and their role

A
  • ADH
  • aldosterone

both ADH/aldosterone stimulate NKCC pumps: promote reabsorption of Na+ to increase the medullary interstitial osmolarity so that water in LATER nephron segments - i.e the the collecting ducts is reabsorbed

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
22
Q

what segments of the nephron dilute the nephron

23
Q

what are the pharmacuetical regulators of the NCC channel?

A

thiazide diuretics

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)

overall: NaCl reabsorbed, H+ and K+ secreted

25
Q

discuss the endogenous regulation at the cortical collecting tubule

A
  • aldosterone:
    • increases NaK ATPase activity at principle cells
    • increases synthesis/insertion of Na+ channels
      • thus, it increases all movements dependent on Na+: Na+, Cl reabsorption, and K+/H+ secretion
  • ADH
    • increases permeability to water so that it can follow Na+ into tubule
26
Q

discuss permeability & solute movement that medullary collecting ducts:

A
  • solute movement parallels that of the cortical collecting tubules
    • NaCl reabsorbtion/K + secretion in principle cells
      • water follows Na+ (isotonic)
    • H+ secetion from intercalated cells
27
Q

endogenous regulation of medullary collecting tubules

A

hypovolemic state (aldosterone, ADH release), hypervolemic state (ANP, BNP released)

  • aldosterone - increases Na+/Cl- reabsoption, K+/H+ secretion
  • ADH - enhances isotonic water reabsorption
  • ANP, BNP & urodilatin:
    • INHIBITS Na+ reabsorption and thus water reabsorption
28
Q

on what parts the nephron does aldosterone act?

A
  • increases Na+ and Cl- (and water) reabsorption & K+ and H+ secretion in the cortical & medullary collecting ducts,
    • is the primary determinent of K+ excretion
      • ​excess aldosterone secretion can thus lead to hypokalemia
    • increases the isoosmotic reabsorption of water
29
Q

on what part of the nephron ADH (vasopressin) act and what does it do?

A
  • stimulates NKCC pump in thick ascending limb promoting Na+, Cl, Ca++, Mg++ reabsorption
  • increases permeability of cortical and medullary to water
    • also increases permeability of medullary collecting tubule to urea

S2B5 Physiology (10 decks)

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