Harrison-Bernard, Lisa
Renal Physiology - Lectures Physiology of Body Fluids – PROBLEM SET, RESEARCH ARTICLE Structure & Function of the Kidneys Renal Clearance & Glomerular Filtration– PROBLEM SET RltifRlBldFlRegulation of Renal Blood Flow - REVIEW ARTICLE 5. Transport of Sodium & Chloride– TUTORIAL A & B 6. Transport of Urea, Glucose, Phosphate, Calcium & Organic Solutes 7. Regulation of Potassium Balance 8. Regulation of Water Balance 9. Transport of Acids & Bases 10. Integration of Salt & Water Balance 11. Clinical Correlation – Dr. Credo 12. PROBLEM SET REVIEW – May 9, 2011 13. EXAM REVIEW – May 9, 2011 14. EXAM IV – May 12, 2011
Renal Physiology Lecture 5 Transport of Sodium and Chloride Chapter 4 Koeppen & Stanton Renal Physiology 1. Na+ BlBalance 2. Na+ Transport Mechanisms 3. Cl- Transport Mechanisms 4. Glomeru lo tu bu lar (G-T) Balance 5. Hormonal Control
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** Renal Failure Patient ** Patient Data Normal
PlasmaK+
PUrea BP
PPO4- Hematocrit
PHCO3-
PpH
PCa2+
Filtration and Reabsorption ~ Table 4.1 Amount Amount % FILTER/d EXCRETE/d REABSORB
√ Water (L) 180 1.8 99.0 K+ (mEq) 720 100 86. 1
Ca2+ (mEq) 540 10 98.2
- HCO3 (mEq) 4,320 2 99.9+
* Cl- ((q)mEq) 18,000 150 99.2 * Na+ (mEq) 25,500 150 99.5
Glucose (mmol) 800 0 100
Urea (mmol) 1,125 450 60
Medical Physiology 2011 Renal 5 2 Harrison-Bernard, Lisa
Na+ Intake = Na+ Loss Intake Per Day Food 2.8 g Output Sweat ~ 0.3 g Feces ~ 0.1 g Urine 2.4 g 2.8 g
IN OUT Distribution & Balance of Na+ OUT
OUT OUT Must = IN
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TIME FOR SHOW & TELL Amount of NaCl: • Filtered Load . 1,500 g/d • Contained in ECF • 140 g • Excreted in Urine • 6 g
Determinants of Na+ Excretion Amount excreted/min = Amount filtered/min – amount reabsorbed/min . UNa x V = PNa x GFR – Tubule Transport
140 mM * REGULATED * (changes little)
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Renal Physiology Lecture 5
• Na+ BlBalance • Na+ Transport Mechanisms • Cl- Transport Mechanisms • Glomerul ot ub ul ar (G -T) Balance • Hormonal Control
Na+ Reabsorption - Active Process • ALL tubular segments EXCEPT descending limb LOH (impermeable to NaCl) • Basolateral Na+/K+- ATPase -unidirectional Na+ extrusion tubular epithelial cells → peritubular interstitium • ALL Na+-reabsorbing nephron segments pumps Na+ & K+ AGAINST concentration gradients
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Coupling of H2O & Na+ Reabsorption
1. Na+ - downhill from tubular lumen , across epithelial cell, pumped into interstitial fluid 2. Tubular fluid Osm - interstitial fluid Osm
3. Net diffusion H2O from lumen tubular cell plasma membranes and/or tight junctions interstitial fluid + 4. H2O, Na , etc. move together bulk flow peritubular capillaries
Route of Na+ Reabsorption ~ Fig 4-8 Paracellular Tubular Lumen to Cell Na+ moves DOWN electrical & chemical gradient
Transcellular
Pumped out cell UPHILL
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Renal Handling of Na+ ~ Table 4-4 Filtered Load Na+ 25,500 mmol/d
1,300 mmol/d 3 100% 5% of filtered load remaining 8% 17,000 mmol/d 1 remaining 67% of filtered load 33% 3% remaining remaining
2 6,400 mmol/d 25% of filtered load 700 mmol/d 4 <3% of filtered load
. V = 1.5 L/d Urinary Na+ excretion 100 mmol/d U = 67 mmol/L Na 0.4% of filtered load
Which patients would benefit from drugs tha t bl oc k Na+ transporters?
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Patients with:
• Hypertension • Heart failure • Edema • Kidney disorders • Cirrhosis of liver
Glomerular Filtration And Tubular Transit • Munich-Wistar rat • Lucifer yellow iv bolus
• Glomerulus • Bowman’s Capsule • Proximal Tubule • Distal Tubule
• Images are optical sections acquired with multip ho ton confoca l fluorescence microsco py using photomultiplier detectors • Peti-Peterdi 2006
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Lumen Na+ Cotransport - Early Proximal Tubule Fig 4-2 2 3 + Na+ Na 1. Na+ moves H+ down gradient, - HCO3 pulls glucose into cell against its gradient 2. Na+-H+ 1 3 antiporter Na+ Na+ (NHE3) Glucose 3. Na+ pumped Glucose out Na+-K+- Acetozolamide - diuretic ATPase
Na+ Cotransport – Late Proximal Tubule Fig 4-4 Lumen - - 1. High [Cl ] Cl 1 lumen driving Na+ 3 force – passive + + diffusion of Na 2 Na NaCl - paracellular Cl- 2. Na+-H+ antiporter 3. Na+ pumped out cell Na+- K+-ATPase
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Solute Composition Along the Proximal Tubule ~ Fig 4-3 Ratio increases if 1 NOT reabsorbed
same as H2OorO, or secreted 3 1. High for Inulin 2. Low for Glucose, AiAmino ac ids, - HCO3 2 3. Unchanged Na+, isosmotic ~ 1
Na+ Transport - Thick Ascending Limb (TAL) Fig 4-8 Lumen Na+ 1 1. Na+/K+/2Cl- 3 (NKCC2) - Na+ Na+ move down Na+ conc gradient - + electroneutral H 2 2. Na+-H+ Na+ 4 antiporter 3. Na+ pumped out Na+-K+- H2O ATPase + NKCC2 – loop diuretics - Lasix4. Na paracellular
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Na+ Transport – Early Distal Convoluted Tubule Fig 4-9
Lumen 1. Na+/Cl- cotransporter (NCC) + 1 2 + Na Na+ Na moves down conc Cl- gradient - H2O electroneutral 3 2. Na+ pumped out Na+-K+-ATPase
NCC – thiazide diuretics 3. H2O impermeable
Na+ Transport – Cortical Collecting Duct – Principal Cell Fig 4-10 Lumen 1. Epithelial Na+ Na+ Channel (ENaC) – 1 2 voltage-gated Na+ Na+ channel 2. Na+ pumped out Na +-K+- ATPase ENaC Blocked by Amiloride 3. H2O depends on AQP2
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Renal Physiology Lecture 5
1. Na+ Balance 2. Na+ Transport Mechanisms 3. Cl- Transport Mechanisms 4. Glomerulotubular (G-T) Balance 5. Hormonal Control
Cl- Cotransport – Late Proximal Tubule Fig 4-4
Lumen 1. High [Cl-] lumen Cl- 1 driving force – chemical gradient passive diffusion of Cl- paracellular 2. Lumen-negative + 2 Cl- Cl- b/c Na cotransporters - favorable electrical gradient for passive Cl- reabsorption
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Cl- Transport - Thick Ascending Limb (TAL) Fig 4-8 1. Na+/K+/2Cl- Lumen (NKCC2) Cl- moves 1 2 down conc Cl- 2Cl- gradient electroneutral transcellular ONLY 2. Cl- channel BL
Cl- Transport – Early Distal Convoluted Tubule Fig 4-9 Lumen 1. Na+/Cl- cotransporter 1 (NCC) Cl- moves - Cl down conc gradient - 2 Cl- electroneutral 2. Cl- channel BL
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Regulation of Na+ and Cl- Transport 1. Glomerulotubular Balance – physical & lilluminal ftfactors 2. Aldosterone, SNS, AVP • Na+ reabsorption 3. ANP, P rost agl andi ns, Bradykinin, Dopamine • Na+ reabsorption
Renal Physiology Lecture 5
1. Na+ Balance 2. Na+ Transport Mechanisms 3. Cl- Transport Mechanisms 4. Glomerulotubular (G-T) Balance 5. Hormonal Control
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Glomerulotubular (G-T) Balance IS NOT Tubuloglomerular Feedback (TGF)
Glomerulotubular G-T BALANCE • Spontaneous Δ GFR = Δ filtered load Na+ • Must rapidly alter Na+ transport so… NO Δ Na+ excretion • ** PT reabsorbs a CONSTANT FRACTION of filtered Na + =67%**= 67% ** • Starling forces = oncotic & hydrostatic pressure difference between PTC & interstitial space
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Glomerulotubular G-T BALANCE
• Physical: GFR = PC – reabsorption peritubular capillaries (Starling forces) • Luminal: Na+ reabsorption as tubular flow – processes NOT readily saturated Net effect: impact of filtered load on delivery to distal nephron
Glomerular Tubular BALANCE
Normal GFR PPC =20
PC =35 FF
PPC =17
Site - PTC
PC =40 **
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Renal Physiology Lecture 5
1. Na+ Balance 2. Na+ Transport Mechanisms 3. Cl- Transport Mechanisms 4. Glomerulotubular (G-T) Balance 5. HlCtlHormonal Control – Aldos terone (AngII, SNS (NE), AVP, ANP, Prostaglandins, Bradykinin, Dopamine)
Aldosterone • Steroid hormone • Promotes Na+ entry apical Na+ channels - ENaC Na-K-ATPase protein ENaC protein activity enzymes Krebs cycle ATP and energy Na-K- ATPase pump * Na+ Reabsorption *
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Summary Hormonal Control Na+ Antinatriuretic Na+ Reabsorption Na+ Excretion Aldosterone AngII SNS AVP Natriuretic Na+ Reabsorption Na+ Excretion ANP Prostaglandins Bradykinin Dopamine
* * MAJOR Apical Na+ Transport * * APICAL BASOLAT
+ Peritu Na ATP aa,gluc etc. 3Na+
Proximal tubule b
Na+ ular capillary/v 2K+ H+ ADP Na+ K+ 2Cl- Thick ascending limb Na+ H+ a
Na+ sa recta Distal convoluted tubule Cl- Collecting duct Na+ (Principal cell)
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Summary 1. Hormonal regulation of Na+ transport to maintain ECFV & BP + 2. Na reabsorption – active H2O reabsorption - passive 3. GLOMERULAR TUBULAR (GT) BALANCE - stabilizes fractional Na+ reabsorption by PT as ∆ filtered load Na+ 4. Proximal Tubule Transport Model - Posted
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