lec 28 - sodium and water

important places for sodium reabsorption

PCT (66%) - SGLT (glucose), Na+/H+ exchanger (NHE), trans and paracellular

TAL (25%) - Na+/K+/2Cl- co-transporter (NKCC2), trans and paracellular

DCT (5%) - Na+/Cl- cotransporter, transcellular only

CCT (3%) - ENaC, transcellular only, hormonal control - aldosterone 

sodium re-absorption - PCT

66%

leaky epithelium - tight junction permeable to Na+ and water

trans- and para- cellular re-absorption of Na+

isotonic reabsorption (equal amounts of sodium and water)

note that chloride will follow the sodium

sodium reabsorption in the TAL

25%

semi-tight epithelium - only permeable to Na+/not permeable to water

trans and para cellular reabsorption 

loop diuretics (furosemide) inhibit NKCC2, increase diuresis 

note there is also potassium channels at apical surface to make sure there is enough potassium for the transporter 

sodium reabsorption in the DCT 

5% 

tight epithelium 

transcellular re-absorption of Na+ (no paracellular transport) 

diuretics (thiazides) inhibit NCC = mild diuresis 

filtered sodium reabsorption in the CCD

3%

tight epithelium 

transcellular reabsorption of Na+ (no paracellular transport)

regulated by aldosterone - increases ENaC expression and insertion into membrane 

upregulates Na/K ATPase 

diuretics (amiloride) inhibit ENaC, very mild diuresis 

aldosterone

from the zona glomerulosa of the adrenal gland

binds to minerocorticoid receptor

alters gene expression

upregulation of ENaC and Na+/K+ATPase

de nvo synthesis of ENaC, Na+/K+ATPase and other proteins (genomic effects)

how does aldosterone get turned off

high plasma volume results in the release of ANP from cardiac atria

high plasma ANP levels reduce plasma aldoterone, increase GFR, reduce Na+ reabsorption, increase Na+ excretion

important places where water is reabsorbed

PCT - 66%

loop of henle - 25%

CD - ~2-8% 

aquaporins throughout the nephron

AQP1 in PCT and descending thin limb - both apical and basolateral

CCD - AQP2 in the principal cells of collecting duct - apical membrane, AQP3 in the prinicpal cells basolateral membrane

AQP4 - inner medullary collecting duct, basolateral membrane

water reabsorption - PCT

66% of filtered load

driven by Na+ reabsorption - isotonic

transcellular via AQP1, paracellular via leaky tight junctions

water reabsorption in th thin descending loop of Henle

transcellular re-absorption of H2O

high levels of AQP1 

secondary bulk reabsorption, more regulated, AQP1, transcellular not paracellular 

water reabsorption - collecting duct

tight epithelium - no paracellular transport, no unregulated transport

water reabsorption in the prinicipal cell of the CCT is regulated by ADH (vasopressin) 

hormonal control of water reabsorption in the CCT

ADH released in response to low BP (baroreceptors), high blood osmolarity (osmoreceptors), increased ATII

circulating ADH binds to V2 receptor on basolateral membrane of CD cells 

activated adenylyl cyclase, increased cAMP, activates PKA, phophorylation leads to sub-apical AQP2 vesicles moving to membrane via exocytosis 

increased apical membrane water permeability 

water homeostasis

we have a fast and slow system to regulate water homeostasis

fast: reacts to changes in osmolarity

slow: reacts to changes in volume

overall water and Na+ reabsorption diagram

water reabsorption and vasopressin diagram

renal sodium regulation summary

high plasma volume results in the release of ANP from cardiac atria

high plasma ANP levels reduce plasma aldosterone, increase GFR, reduce Na+ reabsorption, increase Na+ excretion