L8 - Renal Clearance Concepts Flashcards
What is the average renal blood flow?
1.1L/min = 1100mL/min
How would you describe the flow of blood supply?
Renal artery –> interlobular arteries –> arcuate –> interlobular arterioles that perfuse the individual nephrons.
What is the functional subunit of the kidney, and what are the different components in the nephron?
nephron.
glomerulus, proximal renal tubule, loop of Henle, distal tubule, and collecting tubule.
Describe the filtration and urine flow processes.
- 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.
What are the three processes that govern urine formation and renal clearance, and in what order do they present?
glomerular filtration –> tubular secretion –> tubular absorption
Describe the extent of efficiency of glomerular filtration
low efficiency (only 11% of renal blood flow is filtered).
(T/F): only unbound drug in plasma water is filtered.
true. protein-bound drugs are too large to get filtered through the fenestration of the glomerulus.
How do you calculate rate of filtration, and what are the units that it is expressed in?
rate of filtration = fu x GFR x C
expressed in mg/min.
(similar to the rate of elimination)
How do you calculate rate of filtration if drug is only filtered?
rate of excretion = rate of filtration = CLr = CLf = fu x GFR
When will Clr = Clf?
when drug is only filtered.
renal clearance = filtration clearance
rate of excretion = rate of filtration
How to calculate renal clearance?
renal clearance = (1-Fr)(CLf + CLs)
Rate of excretion = rate of clearance (T/F)?
False. rate of excretion = rate of clearance x concentration
rate of excretion = (1-Fr) (rate of filtration + rate of secretion)
Why is GFR such a good estimate of renal performance?
GFR is relatively stable and insensitive to changes in renal blood flow for healthy individuals.
Why is glomerular filtration of low efficiency?
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
Where does active tubular secretion occur?
At the apical and basolateral membranes of the proximal renal tubule.
When does renal clearance decrease?
when 2 drugs are competing to bind to the same transporter.
When is active secretion inferred?
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
When is tubular reabsorption inferred?
when CLr < fu x GFR (CLr < CLf)
renal clearance < filtration clearance
What is the influence on protein binding for drugs with low Er?
- 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
What is the influence on protein binding for drugs with high Er?
- CLs is less dependent on fu and relatively dependent on perfusion.
Why can renal blood clearance of PAH (para-aminohippuric acid) be used as a diagnostic test for renal blood flow?
- CLb, r = Qr x Er
- Since Er of PAH is close to 1, renal blood clearance is almost equivalent and limited by Qr.
Note that drugs are rarely “highly extracted” in kidneys. Why?
Drugs are usually hydrophobic and become good substances for the kidneys to metabolise.
How are endogeneous compounds and exogeneous compounds reabsorbed?
endogeneous compounds - active reabsorption
exogeneous compounds - passive diffusion
What does the degree of passive absorption depend on?
- size
- lipophilicity (logP)
- urine flow
- urine pH
- state of ionisation of drugs
Urine flow always has a substantial effect on renal clearance (T/F)?
False. It only has a substantial effect when most of the drug is reabsorbed.
What is the relationship between urine flow and renal clearance?
as urine flow increases, renal clearance increases as well
What is urine pH affected by?
diet, drugs and clinical state of patients
What is the effect of urine pH on the renal clearance of bases?
- 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
What is the effect of urine pH on renal clearance of acids?
- 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
What are the effects of both urine pH and flow on drugs?
- 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.
