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

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Presentation on theme: "Renal regulation of sodium balance Stephen P. DiBartola, DVM Department of Veterinary Clinical Sciences College of Veterinary Medicine Ohio State University."— Presentation transcript:

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 tubulesSodium 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 cellsEnergy 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 membranesNa + -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 tubules67% of filtered load reabsorbed in proximal tubules 25% of filtered load reabsorbed in loop of Henle25% of filtered load reabsorbed in loop of Henle 5% of filtered load reabsorbed in distal convoluted tubule and connecting segment5% of filtered load reabsorbed in distal convoluted tubule and connecting segment 3% of filtered load reabsorbed in collecting duct3% 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 entryLuminal entry Co-transport with glucose, amino acids, P iCo-transport with glucose, amino acids, P i Na + -H + antiporterNa + -H + antiporter Basolateral exitBasolateral exit Na + -K + ATPaseNa + -K + ATPase Tubular fluid Cl - concentration increasesTubular 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 lumenThin descending limb: Passive NaCl entry into tubular lumen Thin ascending limb: Passive NaCl reabsorptionThin ascending limb: Passive NaCl reabsorption

8 Sodium reabsorption: Thick ascending limb of Henle’s loop Luminal entryLuminal entry Na + -H + antiporterNa + -H + antiporter Na + -K + -2Cl - cotransporter (site of action of furosemide and bumetanide)Na + -K + -2Cl - cotransporter (site of action of furosemide and bumetanide) Basolateral exitBasolateral exit Na + -K + ATPaseNa + -K + ATPase Tubular lumen strongly positive relative to peritubular interstitiumTubular 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 entryLuminal entry Passively via Na + channel (site of action of amiloride and triamterene)Passively via Na + channel (site of action of amiloride and triamterene) Basolateral exitBasolateral exit Na + -K + ATPaseNa + -K + ATPase Lumen-negative TEPD generated by Na + movement facilitates Cl - reabsorptionLumen-negative TEPD generated by Na + movement facilitates Cl - reabsorption

11 Renal regulation of sodium balance Extracellular fluid volume is directly dependent on body sodium contentExtracellular 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”)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)Low pressure mechanoreceptors (“volume” receptors) AtriaAtria Pulmonary vesselsPulmonary vessels High pressure baroreceptors (“pressure” receptors)High pressure baroreceptors (“pressure” receptors) Aortic archAortic arch Carotid sinusCarotid sinus Afferent arterioles of glomeruliAfferent arterioles of glomeruli

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

14 Control of renal sodium reabsorption Glomerulotubular balanceGlomerulotubular balance AldosteroneAldosterone Peritubular capillary factors (Starling forces)Peritubular capillary factors (Starling forces) OtherOther CatecholaminesCatecholamines Angiotensin IIAngiotensin II Atrial natriuretic peptideAtrial natriuretic peptide “Pressure” natriuresis“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)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 ingestionThis 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, bicarbonateSpontaneous 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 facilitatedSpontaneous 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 AldosteroneAldosterone Alters renal Na + reabsorption in response to dietary fluctuationsAlters renal Na + reabsorption in response to dietary fluctuations Main stimuli for release: Angiotensin II, hyperkalemia, ACTHMain 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 ductsMain 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) Increased Na + intake: ECF expansionIncreased Na + intake: ECF expansion GFR & RPF increase proportionately (FF unchanged)GFR & RPF increase proportionately (FF unchanged) Decreased Na + intake: ECF contractionDecreased Na + intake: ECF contraction RPF decreases more than GFR (FF increased)RPF decreases more than GFR (FF increased) Think of the effects on P and 

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

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

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

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

23 “Pressure” natriuresis Renal Na + and water excretion are increased when renal arterial pressure increases without change in GFRRenal 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 inputMechanism 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 balanceOsmolality of ECF and serum sodium concentration are regulated by adjusting water balance Water output: Anti-diuretic hormone (vasopressin)Water output: Anti-diuretic hormone (vasopressin) Water intake: ThirstWater intake: Thirst

25 Regulation of water balance SensorsSensors Osmoreceptors in hypothalamusOsmoreceptors in hypothalamus EffectorsEffectors Anti-diuretic hormone (vasopressin)Anti-diuretic hormone (vasopressin) Increases permeability of cortical and medullary collecting ducts to water and medullary collectiong ducts to ureaIncreases 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)Plasma hypertonicity (1 to 2% increase leads to maximal ADH release) Volume depletion (5 to 10% decrease facilitates ADH release)Volume depletion (5 to 10% decrease facilitates ADH release) OtherOther NauseaNausea PainPain AnxietyAnxiety DrugsDrugs

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


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