1. Renal regulation of sodium balance
Stephen P. DiBartola, DVM
Department of Veterinary Clinical Sciences
College of Veterinary Medicine
Ohio State University
Columbus OH 43210

2. Renal handling of sodium
Sodium is filtered by the glomeruli and reabsorbed by the tubules
Energy for sodium transport in the kidney is required for the Na+-K+ ATPase located in the basolateral membranes of the tubular cells
Na+-K+ ATPase maintains the low intracellular sodium concentration that facilitates sodium entry at the luminal membranes

3. Renal handling of sodium
67% of filtered load reabsorbed in proximal tubules
25% of filtered load reabsorbed in loop of Henle
5% of filtered load reabsorbed in distal convoluted tubule and connecting segment
3% of filtered load reabsorbed in collecting duct

4. Mechanisms for sodium reabsorption differ in different parts of the nephron

5. Sodium reabsorption: Early proximal tubule
Luminal entry
Co-transport with glucose, amino acids, Pi
Na+-H+ antiporter
Basolateral exit
Na+-K+ ATPase
Tubular fluid Cl- concentration increases

6. Sodium reabsorption: Late proximal tubule
Luminal entry
Na+-H+ antiporter in parallel with Cl--Anion- antiporter (H+-Anion- recycled)
Basolateral exit
Na+ actively via Na+-K+ ATPase
Cl- passively via Cl- channel

7. Sodium reabsorption: Thin limb of Henle’s loop
Thin descending limb: Passive NaCl entry into tubular lumen
Thin ascending limb: Passive NaCl reabsorption

8. Sodium reabsorption: Thick ascending limb of Henle’s loop
Luminal entry
Na+-H+ antiporter
Na+-K+-2Cl- cotransporter (site of action of furosemide and bumetanide)
Basolateral exit
Na+-K+ ATPase
Tubular lumen strongly positive relative to peritubular interstitium

9. Sodium reabsorption: Distal convoluted tubule
Luminal entry
Na+-Cl- cotransporter (site of action of thiazide diuretics)
Basolateral exit
Na+ via Na+-K+ ATPase
Cl- via Cl- channel

10. Sodium reabsorption: Connecting segment and collecting duct
Luminal entry
Passively via Na+ channel (site of action of amiloride and triamterene)
Basolateral exit
Na+-K+ ATPase
Lumen-negative TEPD generated by Na+ movement facilitates Cl- reabsorption

11. Renal regulation of sodium balance
Extracellular fluid volume is directly dependent on body sodium content
Adequacy of body sodium content is perceived as the fullness of the circulating blood volume (“effective circulating volume”)

12. Sensors for control of sodium balance
Low pressure mechanoreceptors (“volume” receptors)
Atria
Pulmonary vessels
High pressure baroreceptors (“pressure” receptors)
Aortic arch
Carotid sinus
Afferent arterioles of glomeruli

13. Effectors for control of sodium balance: the KIDNEY
Filtration?
NO: Autoregulation of GFR, tightly regulated serum Na+ concentration
Reabsorption?
YES: Several overlapping mechanisms insure control of Na+ balance

14. Control of renal sodium reabsorption
Glomerulotubular balance
Aldosterone
Peritubular capillary factors (Starling forces)
Other
Catecholamines
Angiotensin II
Atrial natriuretic peptide
“Pressure” natriuresis

15. Glomerulotubular balance
As spontaneous (primary) fluctuations in GFR occur, absolute tubular reabsorption of filtered solutes changes in a similar direction (i.e. the fraction of the filtered load that is reabsorbed remains constant)
This effect does NOT occur when a compensatory (secondary) fluctuation in GFR occurs in response to changes in sodium and water ingestion

16. Glomerulotubular balance: Mechanisms
Spontaneous increase in GFR would increase filtered load of glucose, amino acids, and phosphate, bicarbonate
Spontaneous increase in GFR would increase filtration fraction and alter peritubular Starling forces such that water and solute reabsorption in the proximal tubules would be facilitated

17. Aldosterone
Alters renal Na+ reabsorption in response to dietary fluctuations
Main stimuli for release: Angiotensin II, hyperkalemia, ACTH
Main effect: Increases number of open luminal Na+ channels and activity and number of basolateral Na+-K+ ATPase pumps in principal cells of collecting ducts

18. Peritubular capillary factors (Starling forces)
Think of the effects on P and 
Increased Na+ intake: ECF expansion
GFR & RPF increase proportionately (FF unchanged)
Decreased Na+ intake: ECF contraction
RPF decreases more than GFR (FF increased)

19. Peritubular capillary factors (Starling forces)
Think of the effects on P &  when FF increases
Increased Na+ intake: ECF expansion
GFR & RPF increase proportionately (FF unchanged)
Decreased Na+ intake: ECF contraction
RPF decreases more than GFR (FF increased)

20. Catecholamines
Efferent > afferent arteriolar constriction (increased FF) results in changes in peritubular Starling forces that facilitate Na+ reabsorption
Direct stimulation of proximal tubular Na+ reabsorption
Stimulation of renin release

21. Angiotensin II
Efferent > afferent arteriolar constriction (increased FF) results in changes in peritubular Starling forces that facilitate Na+ reabsorption
Direct stimulation of Na+-H+ antiporter in proximal tubules
Stimulates aldosterone secretion from adrenal glands

22. Atrial natriuretic peptide
Stimulus for release is atrial distension caused by volume expansion
Inhibits Na+ reabsorption in some parts of the collecting duct
Directly increases GFR
Inhibits renin and aldosterone secretion

23. “Pressure” natriuresis
Renal Na+ and water excretion are increased when renal arterial pressure increases without change in GFR
Mechanism is intra-renal and does not require neural or endocrine input

24. Regulation of water balance
Osmolality of ECF and serum sodium concentration are regulated by adjusting water balance
Water output: Anti-diuretic hormone (vasopressin)
Water intake: Thirst

25. Regulation of water balance
Sensors
Osmoreceptors in hypothalamus
Effectors
Anti-diuretic hormone (vasopressin)
Increases permeability of cortical and medullary collecting ducts to water and medullary collectiong ducts to urea

26. Stimuli for ADH release
Plasma hypertonicity (1 to 2% increase leads to maximal ADH release)
Volume depletion (5 to 10% decrease facilitates ADH release)
Other
Nausea
Pain
Anxiety
Drugs

27. Review of renin-angiotensin system (RAS)
Synthesized by granular cells of JGA
Release stimulated by decreased renal perfusion pressure, increased sympathetic tone, decreased delivery of Cl- to macula densa
Release inhibited by angiotensin II
Converts angiotensinogen to angiotensin I (A-I)
Angiotensin II
Prodcued by action of converting enzyme on A-I
Arteriolar vasoconstriction throughout body
Enhances renal excretion of Na+ and water