Na Balance

Early PCT

• basolateral side = primary active transport

  • ­3 Na⁺ out, 2 K⁺ in via ATPase

  • ­Forms osmotic gradient to pull water

  • ­Forms a Na⁺ gradient due to lack of apical channels in early nephron

  • this Na gradient drives secondary active transport

• Transcellular: secondary active, paired w other solutes

  • 100% of glucose, most of our bicarb and AA are reabsorbed here. Since Na+ reabsorption is coupled to these process, the bulk of our Na+ is also reabsorbed here. 

  • Na/H exchaner on apical side

Late PCT

• Paracellular transport across junctions in response to tubular fluid charge

• Now Na is co transported w Cl

• MAJOR CL REABSORPTION HERE

•  Chlorine reabsorbed paracellularly

  • when anions are secreted/exchanged for Cl^-

  • anions ­Binds H⁺ and neutralizes charge (Bicarb)

  • ­Lack of filtered bicarbonate = hyperchloremia

Thin descending limb

• permeable to water, impermeable to solutes

• hyperosmotic interstitium

  • ­water is pulled out of ultrafiltrate (reabsorbed) to dilute interstitium

  • decreases tubular fluid vol = increased osmolarity

  • solute amount stays same

Thin ascending limb

• Permiable to solutes, impermiable to water

  • NO VOL CHANGES

• Na and Cl passively reabsprbed due to concentration diff

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Thick ascending limb

• impermiable to water

• ­solutes are active, passive, paracellular and transcellular transported

• solute concentrations is lower in ultrafiltrate = solutes are activley transported and reabsorbed

• generate hyperosmotic tissue gradient

•  Paracellular transport in response to voltage difference

  • ­Reabsorption of most positively charged ions

•  Na-K-2Cl symporter

  • reabsorbes Na, K, and 2 Cl

  • Active transpoerter : NKCC

  • ­Activity dependent on tubular K⁺ levels

    • K⁺ enters cell but leaks back out to keep lumen positively charged

  • loop diaretics (lasix) block this and cause diuresis and loss of potassium, blocks 25% of Na reabsorption @ loop so its reabsorbed later in nephron

DCT

• Impermiable to water

• Active, passive, paracellular and transcellular transport

•  macula Densa and juxta-glomerular apparatuses

• Na-Cl symporter

  • active transporter : NCC

  • Thiazide block this, potent antihypertensive, block 5% of Na reabsorpsion @ DCT causes Na+ to be reabsorbed via CHANNEL = neg grad

  • Not responsive the tubular K⁺ levels

  • Major fine tune action on sodium reabsorption

Late DCT and Collecting ducts

• Variably permeable to water

• ­Responds to ADH

• ­Tubular fluid is negative

• Reabsorbs NaCl and water isosmotically

• Secretes K⁺ and acid or bicarbonate if needed

• Principle Cells

  • regulating NaCl, K+ and water transport

  • Lots of active transport

  • ­Na-K pump is VERY sensitive to Na⁺ levels

  • ­Apical Na⁺ (ENaC) and K⁺ channels are present

  • ­Cl^- follows Na⁺

• Aldosterone increases Na-K pump

  • ­opens apical Na⁺ channels

  • ­ROMK electroneutral converse to Enac

  • BK or Maxi-K affected by volume, cilia, kaluresis

  • Spironolactone blocks aldosterone from binding

  • Amiloride blocks ENaC

PCT reabsorption of Cl

• almost all transcellular transport

• Most Na⁺ is reabsorbed with Cl^- to balance charges.

• Tubular fluid is negatively charged and Na⁺ is being actively brought into the interstitial space

  • causes water to move in and Cl goes w it

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Water reabsorption

• Most water is reabsorbed passively and secondary to solutes Due to osmotic or pressure forces

• Starling Forces

  • ­Pressure drops from glomerulus to peritubular capillary

  • Peritubular oncotic pressure is high

  • Net filtration from tubule INTO peritubular capillary

• Osmosis

  • Transport of OTHER solutes from tubule into capillaries will osmotically pull water along with it

  • ‘Water follows salt’

Regulation of Sodium & Chloride Transport

• Glomerulo-tubular balance mechanism

  • increasing tubular Na increases reabsorption

• Effective Circulating Volume mechanisms

  • RAAS, ADH, SNS, ANP

• Humoral agents

  • dopamine, Ca and bradykinin

Glomerulo-tubular balance

• Increasing tubular sodium increases reabsorption ­Due to increased re-absorptive starling forces

•  Increasing filtration fraction by increasing GFR (same RBF)

  • ­Increases filtrate in tubule

  • ­Increases peritubular oncotic pressure

  • Reduces peritubular hydrostatic pressure

  • ­Increases reabsorption of water and solutes from tubule

•  Increased tubular flow bends cilia on tubular cells and increases Na⁺ reabsorption

Effective Circulating Volume

• Low ECV = SNS = activates RAAS = inc aldosterone

  • inc Na/K ATPase @ cortical collecting duct

  • inc ENaC = inc Na reabsorption = K secreted =neg electrochemical gradient = inc perfusion pressure

• low ECV inc ADH

  • ADH bind to V2 receptors @ collecting duct to increase free water and urea reabsorption

  • ADH binds to V1receptos to increase vasoconstriction

• High ECV = inc ANP

  • causes natriuresis = inc Na and water excretion

  • causes vasodilation