Renal physiology: counter current multiplier and exchanger, water balance

1. Renal physiology: counter current multiplier and exchanger,water balance Lecture 40 Thursday, April 5, 2007 Refs. Medical Physiology Chapters 32, 34, and 37, Ganong Chapter 38, Ross Chapter 20, and Wheater’s Functional Histology Chapter 16

2. The kidney can produce urine with a wide range of solute concentrations • Osmoles excreted per day • osmoles/day = Uosm x urine output • Dilute urine • 30 mOsm (about one tenth the plasma conc. of ~300 mOsm) • Positive free water clearance • At maximum dilution, volume can be 20 liters/day. • Isosmotic urine • The same tonicity as plasma. • Concentrated urine • 1200 mOsm • Minimum urine volume = 0.5 L/day • Negative free water clearance

3. Anatomy of the medulla MP 32-1C

4. Segmental differences in osmolality of renal tubular fluid • Ultrafiltrate (Bowman’s capsule): isosmotic • PCT: isosmotic • deep Henle’s loop: hypertonic • At cortical end of thick ALH: hypotonic • Final concentration is determined by collecting duct and depends on: • Osmotic gradient in medulla • Release of AVP or ADH from posterior pituitary

5. Changes in osmolality of filtrate MP 37-1

6. Gradient in medulla • Created by counter current multiplier effect of long loops of Henley (juxtamedullary glomeruli) • Thick ALH is relatively impermeable to water • Na+-K+-CL- cotransporter pumps ions into tubular cell • Countercurrent exchanger of vasa recta • Prevents washout of gradient

7. Model for generation of gradientFlow, Pump, EquilibrateGanong 38-17A,B

8. Step 2 Ganong 38-17C,D

9. Step 3 Ganong 38-17E,F

10. Step 4 Ganong 38-17G,H

11. Anatomy of the medulla MP 32-1C

12. A straight-tube vasculature would wash out the concentration gradient MP 37-7

13. Diagram of vasa rectaGanong 38-18

14. Antidiuretic hormone (ADH) determines final concentration of urine • ADH (aka AVP) is released from posterior pituitary when there is a need to conserve water. • ADH causes insertion of aquaporins into apical membrane of collecting tubule cells. • Aquaporins make collecting tubule epithelium permeable to water. • Water leaves collecting tubule due to hypertonicity medullary interstitium. • Urine becomes concentrated. • In absence of ADH, water does not move out of collecting duct and dilute urine is excreted.

15. Production of concentrated urine MP 37-2A

16. Production of dilute urine MP 37-2B

17. Diabetes insipidus • Clinical signs are polydipsia and polyuria; patient becomes dehydrated if deprived of water. • Renal form • ADH is present but the kidney does not respond to it. • Central form • ADH is not made by the hypothalamus OR • ADH is not released from posterior pituitary • Treatment with an analogue of ADH will allow urine concentration.

18. Relationship between urine concentration and urine flow in osmotic diuresis. In a patient with diabetes insipidus, an osmotic diuretic can increase urine flow. Even with maximum ADH, an osmotic diuretic will increase urine flow. Ganong 38-19

19. Mortality/Morbidity • Urinary tract disease is not a major cause of mortality • 35,000 deaths/year attributed to renal disease • 750,000 heart disease • 400,000 cancer • 200,000 stroke • Morbidity is high • Millions per year are affected • 20% women develop UTI • 1% suffer from renal stones • Several billion $ per year for dialysis and transplants

20. Overview of disorders of the urinary system • Kidney nephritis, glomerulonephritis • Ureter ureteritis • Bladder cystitis • Urethra urethritis • UTI urinary tract infection (often lower tract only) • Urolithiasis calculus (plural calculi) can be renal or cystic or both • Urinary tract obstruction

21. Clinical signs of urinary disease • Hematuria • Proteinuria • Azotemia • Pre renal, renal, post renal • Uremia • Volume of urine • Oliguria, anuria • Polyuria, polydipsia • Edema