1. Errata Lecture 10 Slide 18 Rational because However

2. RENAL CLEARANCE Lecture #11

3. Excretion 80% Urine (Kidneys) 20% Bile

4. Renal Blood Flow (Q R ) Kidney Aorta Vena Cava Renal Artery Renal Vein Heart Ureter Bladder Excreted

5. Kidneys Kidney Ureter Bladder Liver Aorta Vena Cava

6. Nephron Renal Vein Renal Artery Kidney Ureter Renal Artery Renal Vein Bowman’s capsule

7. Glomerulus (Filtration) pored glomerular cells basal lamina (X larger proteins) filtration slit pedicel filtration slit podocyte

8. Tubules (Secretion and Reabsorption) Urine Nephron Side View Cross-Section Kidney Blood Plasma Urine

9. Renal Artery Renal Vein Ureter Filtration Secretion Reabsorption Excretion (Urine) Factors that Influence Renal Clearance

10. Rate of Excretion

11. Renal Clearance (CL R ) Clearance by Filtration (called the glomerular filtration rate) Clearance by Secretion Confusing Book Point: GFR is equivalent to CL f

12. Glomerular Filtration Rate [Drug] plasma fraction unbound

13. Flow Rate Approximations

14. Urinary Flow Rate is Highly Variable Urine Flow Rate (UFR) Average = 68 ml/hr Our approximation UFR = 1 ml/hr/kg or 70 ml/hr

15. Renal Extraction Ratio (E R ) Confusing Book Point: They use extraction rate and excretion rate the same.

16. Renal Extraction Ratios (E R )

17. Contributions of filtration and secretion

18. Urine, CL R and E R Reabsorption Filtration Secretion Concentration of Drug in the Urine Urine Flow Rate

19. Factors that Influence (CL R ) pH Altered Secretion Renal Impairment Protein Binding

20. Factors that Influence Passive Diffusion: pH partition hypothesis

21. pH and CL R unionized Membrane Urine Blood Unionized Ionized (Reabsorption Blocked)

23. plant hormone/antipyretic pKa=2.97

24. Urine Acidification and Alkalinization in the Treatment of Drug Overdose Drug is a weak acid – Urine alkalinization (Increase pH) IV sodium bicarbonate – Phenobarbital, Aspirin or Salicylates – Herbicide 2,4-dichlorophenoxyacetic acid poisoning Drug is a weak base – Urine acidification (Decrease pH) IV ammonium chloride – Amphetamines (metabolic acidosis)

25. Altered Active Tubular Secretion Inhibit Tubular Secretion CL R =24 L/hr to 14 L/hr

26. Low E R (Renal Impairment) Anti-seizure

27. Altered Protein Binding *Clofibric acid is a metabolite of the cholesterol-lowering pharmaceutical drug clofibrate.

28. Renal Metabolism (Minor) kidney Pharmacological Reviews March 1, 1998 vol. 50 no. 1 107-142 UDP-glucuronosyltransferase (UDPG) Activity