L8 - Renal Clearance Concepts

Question 1

What is the average renal blood flow?

Answer 1

1.1L/min = 1100mL/min

Question 2

How would you describe the flow of blood supply?

Answer 2

Renal artery –> interlobular arteries –> arcuate –> interlobular arterioles that perfuse the individual nephrons.

Question 3

What is the functional subunit of the kidney, and what are the different components in the nephron?

Answer 3

nephron.

glomerulus, proximal renal tubule, loop of Henle, distal tubule, and collecting tubule.

Question 4

Describe the filtration and urine flow processes.

Answer 4

• Glomerulus filters 120mL of plasma water per minute.
• Blood perfuses proximal and distal tubules through a series of interconnecting channels.
• More of the water is reabsorbed, resulting in a urine flow of 1-2L/min.

Question 5

What are the three processes that govern urine formation and renal clearance, and in what order do they present?

Answer 5

glomerular filtration –> tubular secretion –> tubular absorption

Question 6

Describe the extent of efficiency of glomerular filtration

Answer 6

low efficiency (only 11% of renal blood flow is filtered).

Question 7

(T/F): only unbound drug in plasma water is filtered.

Answer 7

true. protein-bound drugs are too large to get filtered through the fenestration of the glomerulus.

Question 8

How do you calculate rate of filtration, and what are the units that it is expressed in?

Answer 8

rate of filtration = fu x GFR x C
expressed in mg/min.
(similar to the rate of elimination)

Question 9

How do you calculate rate of filtration if drug is only filtered?

Answer 9

rate of excretion = rate of filtration = CLr = CLf = fu x GFR

Question 10

When will Clr = Clf?

Answer 10

when drug is only filtered.
renal clearance = filtration clearance
rate of excretion = rate of filtration

Question 11

How to calculate renal clearance?

Answer 11

renal clearance = (1-Fr)(CLf + CLs)

Question 12

Rate of excretion = rate of clearance (T/F)?

Answer 12

False. rate of excretion = rate of clearance x concentration
rate of excretion = (1-Fr) (rate of filtration + rate of secretion)

Question 13

Why is GFR such a good estimate of renal performance?

Answer 13

GFR is relatively stable and insensitive to changes in renal blood flow for healthy individuals.

Question 14

Why is glomerular filtration of low efficiency?

Answer 14

renal extraction is low (assuming that Cu,b = Cb).
E = GFR / Qr
= 120 / 1100 < 0.1
especially for a drug that is highly bound to plasma

Question 15

Where does active tubular secretion occur?

Answer 15

At the apical and basolateral membranes of the proximal renal tubule.

Question 16

When does renal clearance decrease?

Answer 16

when 2 drugs are competing to bind to the same transporter.

Question 17

When is active secretion inferred?

Answer 17

when CLr > fu x GFR (CLr > CLf)
renal clearance > filtration clearance
as a result of net tubular secretion, some drugs will have high extraction ratio

Question 18

When is tubular reabsorption inferred?

Answer 18

when CLr < fu x GFR (CLr < CLf)

renal clearance < filtration clearance

Question 19

What is the influence on protein binding for drugs with low Er?

Answer 19

• influence of protein binding depends on EFFICIENCY OF TRANSPORT-MEDIATED PROCESS and CONTACT TIME AT SECRETORY SITES ALONG THE TUBULE.
• CLs is dependent on fu, relatively independent on perfusion.
• CLf is also dependent on fu, since CLf = fu x GFR

Question 20

What is the influence on protein binding for drugs with high Er?

Answer 20

• CLs is less dependent on fu and relatively dependent on perfusion.

Question 21

Why can renal blood clearance of PAH (para-aminohippuric acid) be used as a diagnostic test for renal blood flow?

Answer 21

• CLb, r = Qr x Er

- Since Er of PAH is close to 1, renal blood clearance is almost equivalent and limited by Qr.

Question 22

Note that drugs are rarely “highly extracted” in kidneys. Why?

Answer 22

Drugs are usually hydrophobic and become good substances for the kidneys to metabolise.

Question 23

How are endogeneous compounds and exogeneous compounds reabsorbed?

Answer 23

endogeneous compounds - active reabsorption

exogeneous compounds - passive diffusion

Question 24

What does the degree of passive absorption depend on?

Answer 24

• size
• lipophilicity (logP)
• urine flow
• urine pH
• state of ionisation of drugs

Question 25

Urine flow always has a substantial effect on renal clearance (T/F)?

Answer 25

False. It only has a substantial effect when most of the drug is reabsorbed.

Question 26

What is the relationship between urine flow and renal clearance?

Answer 26

as urine flow increases, renal clearance increases as well

Question 27

What is urine pH affected by?

Answer 27

diet, drugs and clinical state of patients

Question 28

What is the effect of urine pH on the renal clearance of bases?

Answer 28

• polar basic drugs that are unionised – renal clearance is independent of pH
• very weakly nonpolar basic drugs with low pKa - renal clearance is low.
• nonpolar basic drugs with moderate to high pKa - renal clearance is dependent on pH

Question 29

What is the effect of urine pH on renal clearance of acids?

Answer 29

• polar acidic drugs in its unionised form – renal clearance is independent on urine pH
• very weak nonpolar acids with low pKa - renal clearance is low.
• nonpolar acidic drugs with moderate to low pKa – sensitive to urine pH

Question 30

What are the effects of both urine pH and flow on drugs?

Answer 30

• acids and bases that show pH-sensitive absorption generally show flow rate dependence.
• extent to which renal clearance is affected by flow depends on its rate of reabsorption.