Clearance

Question 1

How is renal function quantified?

Answer 1

Clearance

GFR

RPF

Fractional excretion

Question 2

What is renal clearance used to measure?

Answer 2

GFR, RPF and determine renal handling of different substances

Question 3

What is renal clearance?

Answer 3

The volume of plasma cleared of a substance is by kidneys per unit time

Question 4

How much urea is excreted per min?

Answer 4

Urea excretion= 6 mg/ml x 2ml/min=12 mg/min

Question 5

What is the clearance of urea?

Answer 5

Urea clearance= 12mg/min/0.2nmg/ml= 60 ml/min

Question 6

For which substances can renal clearance be measured?

Answer 6

Anything and everything that gets fired!
The value obtained will depend on how the substance is handled by kidneys:
-If the substance is not excreted in the urine, it’s clearance = zero -Ex. (Glucose)

• If the substance is filtered and not reabsorbed or secreted in the urine, it’s clearance= GFR
• If the substance undergoes net Reabsorption, it’s clearance will be less than that of Inulin- Ex. (Na+, urea, CL-)
• If the substance undergoes net secretion, it’s clearance will be greater than that if Inulin
• If the substance undergoes net secretion, it’s clearance will be greater than that of inulin-Ex. PAH

Question 7

What is the filtered load?

Answer 7

Excreted amount (Inulin )/(mannitol)

Question 8

How do we know if it’s net secretion or net Reabsorption?

Answer 8

There is net Reabsorption of a substance if excretion is < filtered load

There is net secretion of substance if excretion > filtered load

Question 9

How can we use clearance to measure GFR?

Answer 9

Need a substance(a) with special properties

1. Freely filtered (concentration in Bowman’s space= concentration in plasma)
2. Not reabsorbed
3. Not secreted

Amount 9f a excreted per minute= amount of a filtered per minute

C1 x V1= C2 x V2

Urine concentration of (a) x urine flow rate= Glomerular filtrate concentration of ( a) x GFR

GFa= Pa

GFR= Ua x V/GFa

Question 10

What is Inulin?

Answer 10

• polysaccharide of fructose
• molecular weight about 5000 daltons
• molecular diameter about 3nm

Question 11

What is the clearance of Inulin?

Answer 11

Inulin clearance= GFR
Typical value for GFR is about 120 ml/min
-freely filtered
-not reabsorbed
-not secreted

Inulin is cleared from plasma by filtration alone

Since none of filtered Inulin returns to the plasma, volume of plasma cleared of Inulin per min must equal the volume of plasma filtered per min(=GFR)

About 180 liters/day

Question 12

What are the problems with measuring Cinulin clinically?

Answer 12

• Must be infused intravaneously
• Continual blood sampling required
• Chemical analysis cumbersome

Question 13

What is a useful alternative to Inulin measure clearance clinically?

Answer 13

Creatinine (not creatine)

• Endogenous (by-product of muscle metabolism)
• Released into blood at relatively constant rate (plasma concentration is fairly stable; therefore only need one blood sample)
• Freely filtered
• Not reabsorbed
• Is secreted in small amounts

True Ccr overestimates GFR by 10%-20%

Question 14

What is the use of creatinine?

Answer 14

Plasma & urine creatinine concentration

Ccr= Ucr x V/Pcr

Question 15

What are the 2 drawbacks of creatinine?

Answer 15

• It is also secreted & this increases urinary excretion by 20% , in the numerator of the clearance formula
• The concentration method measures other substances such as glucose leading to increase 20% in the denominator in the clearance formula

Both the numerator & the denominator cancel each other so creatinine clearance is a fairly good approximation 9f GFR

Question 16

What is the formula for creatinine clearance?

Answer 16

Ccr= Ucr x V/(PCR)

BUN normally between 10-20mg/dL

low GFR means renal insufficiency

Question 17

What is renal blood flow?

Answer 17

The volume of blood delivered to the kidney per unit of time

Renal blood flow about 1200 ml/min

Question 18

What is renal plasma flow?

Answer 18

This is a measure of plasma that flows through the kidney per unit of time

Question 19

What is effective renal plasma flow?

Answer 19

About 650 ml/min

Question 20

What is filtration fraction?

Answer 20

Is the fraction filtered & has range of 15%-25%

GFR/RPF= filtration fraction

Question 21

How is RBF & RPF measured?

Answer 21

Clearance of para-amino hippurate= renal plasma flow (RPF)

Para-amino hippurate(PAH)
-organic anion

• freely filtered
• avidly secreted by peritubular capillaries into proximal tubule
• At low plasma concentrations,the combination of filtration and secretion means that all PAH arriving in the renal plasma is excreted in the urine

RBF= RPF/1-hematocrit

Question 22

What substances have important clearance?

Answer 22

Clearance of Inulin=GFR

Clearance of creatinine= about GFR

Clearance of PAH= RPF

Question 23

How are PAH. handling by the kidney?

Answer 23

At low plasma concentrations

Volume of plasma cleared of PAH (CPAH)

= volume of plasma entering kidneys

=renal plasma flow

Question 24

What is the mass balance equation?

Answer 24

Urine flow rate= 1 ml/min

UPAH= 65 mg/ml

PPAH= 0.1 mg/ml

RPF= CPAH= 65mg/ml/0.1mg/ ml x1 ml/min= 650 ml/min

Question 25

How can we quantify tubular function?

Answer 25

Filtered load= GFR x Pz

Reabsorp^n= (GFR x Pz)-(Uz x V)

Secret^n= (Uz x V)-(GFR x Pz)

Excretion = Uz x V

Excretion= filtration- Reabsorption+ secretion

Question 26

What is fractional excretion?

Answer 26

Proportion of the filtered load was excreted= fractional excretion

Fractional excretion of Z (FEz)= rate of excretion of Z/ rate off filtration of Z

Question 27

What is the fractional excretion of Na used to indicate?

Answer 27

FeNa below 1% suggests prerenal-cause of acute renal failure

FeNa above 2% acute tubular necrosis

Fractional excretion of Na is used to assess if the acute renal failure is due to pre-renal or renal. Causes

Question 28

What formulas you need to know?

Answer 28

GFR= Urineinulin x V/Pinulin

RPF= UPAH x V/ PPAH

Filtration fraction= GFR/RPF

RBF= RPF/1-hematocrit