Renal Physiology - Lectures

Transcription

1 Renal Physiology - Lectures Physiology of Body Fluids PROBLEM SET, RESEARCH ARTICLE Structure & Function of the Kidneys Renal Clearance & Glomerular Filtration PROBLEM SET Regulation 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, EXAM REVIEW May 9, EXAM IV May 12, 2011 Renal Physiology Lecture 5 Transport of Sodium and Chloride Chapter 4 Koeppen & Stanton Renal Physiology 1. Balance 2. Transport Mechanisms 3. Cl - Transport Mechanisms 4. Glomerulotubular l l (G-T) Balance 5. Hormonal Control Medical Physiology 2011 Renal 5 1

2 ** Renal Failure Patient ** Patient Data Normal Plasma K+ P Urea BP P PO4- Hematocrit P HCO3- P ph P Ca2+ Filtration and Reabsorption ~ Table 4.1 Amount FILTER/d Amount EXCRETE/d % REABSORB Water (L) K + (meq) Ca 2+ (meq) HCO 3- (meq) 4, * Cl - (meq) 18, * (meq) 25, Glucose (mmol) Urea (mmol) 1, Medical Physiology 2011 Renal 5 2

3 Intake = 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 OUT Distribution & Balance of OUT OUT Must = IN Medical Physiology 2011 Renal 5 3

4 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 Excretion Amount excreted/min = Amount filtered/min amount reabsorbed/min. U Na x V = P Na x GFR Tubule Transport 140 mm (changes little) * REGULATED * Medical Physiology 2011 Renal 5 4

5 Renal Physiology Lecture 5 Balance Transport Mechanisms Cl - Transport Mechanisms Glomerulotubular l l (G-T) Balance Hormonal Control Reabsorption - Active Process ALL tubular segments EXCEPT descending limb LOH (impermeable to NaCl) Basolateral /K + - ATPase -unidirectional extrusion tubular epithelial cells peritubular interstitium ALL -reabsorbing nephron segments pumps & K + AGAINST concentration gradients Medical Physiology 2011 Renal 5 5

6 Coupling of H 2 O & Reabsorption 1. - downhill from tubular lumen, across epithelial cell, pumped into interstitial fluid 2. Tubular fluid Osm - interstitial fluid Osm 3. Net diffusion H 2O from lumen tubular cell plasma membranes and/or tight junctions interstitial fluid 4. H 2 O,, etc. move together bulk flow peritubular capillaries Route of Reabsorption ~ Fig 4-8 Paracellular Tubular Lumen to Cell moves DOWN electrical & chemical gradient Transcellular Pumped out cell UPHILL Medical Physiology 2011 Renal 5 6

7 Renal Handling of ~ Table 4-4 Filtered Load 25,500 mmol/d 1 100% remaining 17,000 mmol/d 67% of filtered load 33% remaining 1,300 mmol/d 5% of filtered load 3 8% remaining 3% remaining 2 6,400 mmol/d 25% of filtered load 700 mmol/d <3% of filtered load 4. V = 1.5 L/d U Na = 67 mmol/l Urinary excretion 100 mmol/d 0.4% of filtered load Which patients would benefit from drugs that t block transporters? Medical Physiology 2011 Renal 5 7

8 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 multiphoton t confocal fluorescence microsco py using photomultiplier detectors Peti-Peterdi 2006 Medical Physiology 2011 Renal 5 8

9 Lumen H Glucose Glucose Acetozolamide - diuretic Cotransport - Early Proximal Tubule Fig moves down gradient, HCO - 3 pulls glucose into cell against its gradient 2. -H + 3 antiporter (NHE3) 3. pumped out -K + - ATPase Cotransport Late Proximal Tubule Fig 4-4 Lumen Cl - 1 Na Cl - 1. High [Cl - ] lumen driving force passive diffusion of NaCl - paracellular 2. -H + antiporter 3. pumped out cell - K + -ATPase Medical Physiology 2011 Renal 5 9

10 Solute Composition Along the Proximal Tubule ~ Fig 4-3 Ratio increases if 1 NOT reabsorbed same as H 2 O, or secreted 3 1. High for Inulin 2. Low for Glucose, Amino acids, HCO Unchanged, isosmotic ~ 1 Transport - Thick Ascending Limb (TAL) Fig 4-8 Lumen 1 H + H 2 O Na + NKCC2 loop diuretics - Lasix 1. /K + /2Cl - (NKCC2) - move down conc gradient - electroneutral 2. -H + antiporter 3. pumped out -K + - ATPase 4. paracellular Medical Physiology 2011 Renal 5 10

11 Lumen Cl - H 2 O 3 Transport Early Distal Convoluted Tubule Fig Na + NCC thiazide diuretics 1. /Cl - cotransporter (NCC) moves down conc gradient - electroneutral 2. pumped out -K + -ATPase 3. H 2 O impermeable Lumen Transport Cortical Collecting Duct Principal Cell Fig Epithelial Channel (ENaC) 1 2 Na + ENaC Blocked by Amiloride voltage-gated channel 2. pumped out -K + - ATPase 3. H 2 O depends on AQP2 Medical Physiology 2011 Renal 5 11

12 Renal Physiology Lecture 5 1. Balance 2. Transport Mechanisms 3. Cl - Transport Mechanisms 4. Glomerulotubular (G-T) Balance 5. Hormonal Control Cl - Cotransport Late Proximal Tubule Fig 4-4 Lumen Cl High [Cl - ] lumen driving force chemical gradient passive diffusion of Cl - paracellular 2. Lumen-negative 2 Cl - Cl- b/c cotransporters - favorable electrical gradient for passive Cl - reabsorption Medical Physiology 2011 Renal 5 12

13 Cl - Transport - Thick Ascending Limb (TAL) Fig 4-8 Lumen 2Cl Cl - 1. /K + /2Cl - (NKCC2) Cl- moves down conc gradient electroneutral transcellular ONLY 2. Cl - channel BL Lumen Cl - Cl - Transport Early Distal Convoluted Tubule Fig Cl - 1. /Cl - cotransporter (NCC) Cl - moves down conc gradient - electroneutral 2. Cl - channel BL Medical Physiology 2011 Renal 5 13

14 Regulation of and Cl - Transport 1. Glomerulotubular Balance physical & luminal l factors 2. Aldosterone, SNS, AVP reabsorption 3. ANP, Prostaglandins, Bradykinin, Dopamine reabsorption Renal Physiology Lecture 5 1. Balance 2. Transport Mechanisms 3. Cl - Transport Mechanisms 4. Glomerulotubular (G-T) Balance 5. Hormonal Control Medical Physiology 2011 Renal 5 14

15 Glomerulotubular (G-T) Balance IS NOT Tubuloglomerular Feedback (TGF) Glomerulotubular G-T BALANCE Spontaneous Δ GFR = Δ filtered load Must rapidly alter transport so NO Δ excretion ** PT reabsorbs a CONSTANT FRACTION of filtered = 67% ** Starling forces = oncotic & hydrostatic pressure difference between PTC & interstitial space Medical Physiology 2011 Renal 5 15

16 Glomerulotubular G-T BALANCE Physical: GFR = PC reabsorption peritubular capillaries (Starling forces) Luminal: reabsorption as tubular flow processes NOT readily saturated Net effect: impact of filtered load on delivery to distal nephron Glomerular Tubular BALANCE Normal GFR P PC =20 PC =35 FF P PC =17 Site - PTC PC =40 ** Medical Physiology 2011 Renal 5 16

17 Renal Physiology Lecture 5 1. Balance 2. Transport Mechanisms 3. Cl - Transport Mechanisms 4. Glomerulotubular (G-T) Balance 5. Hormonal Control Aldosterone (AngII, SNS (NE), AVP, ANP, Prostaglandins, Bradykinin, Dopamine) Aldosterone Steroid hormone Promotes entry apical channels - ENaC Na-K-ATPase protein ENaC protein activity enzymes Krebs cycle ATP and energy Na-K- ATPase pump * Reabsorption * Medical Physiology 2011 Renal 5 17

18 Summary Hormonal Control Antinatriuretic Aldosterone AngII SNS AVP Natriuretic ANP Prostaglandins Bradykinin Dopamine Na+ Reabsorption Excretion Reabsorption Excretion * * MAJOR Apical Transport * * APICAL BASOLAT aa,gluc etc. Proximal tubule 3 K + 2Cl - H + Cl - H + ATP Thick ascending limb ADP Distal convoluted tubule Collecting duct (Principal cell) 2K + Peritub bular capillary/va asa recta Medical Physiology 2011 Renal 5 18

19 Summary 1. Hormonal regulation of transport to maintain ECFV & BP 2. reabsorption active H 2 O reabsorption - passive 3. GLOMERULAR TUBULAR (GT) BALANCE - stabilizes fractional reabsorption by PT as filtered load 4. Proximal Tubule Transport Model - Posted Medical Physiology 2011 Renal 5 19