Errata

Lecture 10Slide 18

Rational

because

However

RENAL CLEARANCELecture #11

Excretion• 80% Urine (Kidneys)• 20% Bile

Renal Blood Flow (QR)

Kidney

AortaVena Cava

RenalArtery

RenalVein

Heart

Ureter

Bladder

Excreted

Kidneys

KidneyKidney

UreterUreter

Bladder

LiverAo

rta

Vena

Cav

a

Nephron

Renal Vein

Renal Artery

Kidney

Ureter

Ureter

RenalArtery

RenalVein

Bowman’s capsule

Glomerulus (Filtration)

pored glomerular cells

basallamina (X larger proteins)

filtration slit

pedicelfiltration slit

podocyte

Tubules (Secretion and Reabsorption)

Urine

Urine

Nephron Side View

Cross-Section

Kidney

BloodPlasma

Urine

RenalArtery

RenalVein

Ureter

Filtration

Secretion

Reabsorption

Excretion (Urine)

Factors that Influence Renal Clearance

Rate of Excretion

Renal Clearance (CLR)

Clearance by Filtration(called the glomerular filtration rate)

Clearance by Secretion

Confusing Book Point: GFR is equivalent to CLf

Glomerular Filtration Rate

[Drug]plasmafraction unbound

Flow Rate Approximations

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

Renal Extraction Ratio (ER)

Confusing Book Point: They use extraction rate and excretion rate the same.

Renal Extraction Ratios (ER)

Contributions of filtration and secretion

Urine, CLR and ER

Reabsorption Filtration Secretion

Concentration of Drug in the Urine

Urine Flow Rate

Factors that Influence (CLR)

• pH• Altered Secretion• Renal Impairment• Protein Binding

Factors that Influence Passive Diffusion: pH partition hypothesis

pH and CLR

unionized

Membrane

UrineBlood

Unionized Unionized

Ionized (Reabsorption Blocked)

plant hormone/antipyretic

pKa=2.97

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)

Altered Active Tubular Secretion

Inhibit Tubular Secretion

CLR =24 L/hr to 14 L/hr

Low ER (Renal Impairment)

Anti-seizure

Altered Protein Binding

*Clofibric acid is a metabolite of the cholesterol-lowering pharmaceutical drug clofibrate.

Renal Metabolism (Minor)kidney

Pharmacological Reviews March 1, 1998 vol. 50 no. 1 107-142

UDP-glucuronosyltransferase (UDPG) Activity