Clearance

[AV6:Chp3]

Clearance

... is the volume of plasma per unit time from which all of a substance is removed

 

Calculation of clearance

Clearance
= (Urine rate x urine conc.) / plasma conc

i.e. Clearance = rate of excretion / plasma conc

 

Factors influencing clearance

• Filterability
• Net reabsorption/secretion
• Metabolism/breakdown in tubular lumen

Examples

Inulin

• Polysaccharide
• Freely filtered
  * Concentration in Bowman's capsule is the same as plasma concentration
• Neither reabsorbed or secreted
• No metabolism in the tubular lumen

 

Thus,

Clearance of inulin
= GFR

Para-aminohippurate (PAH)

• Small water-soluble organic anion
• Freely filtered
• Secreted by proximal tubule
  * Transcellular route
  * Secretion rate saturable

At low plasma concentration

90% of PAH entering kidney is removed from plasma.

 

Thus,

Clearance of PAH
= Effective renal plasma flow
* Slightly less than RPF

 

Creatinine

• Freely filtered
• Not reabsorbed
• Small secretion by proximal tubule

 

Thus,

Clearance of creatinine
= 10-20% higher than GFR

At low GFR

--> The secreted portion of creatinine becomes relatively larger.

Thus,

When GFR is low,

Creatinine clearance more severely overestimates GFR

 

NB:

• Creatinine is an end product of creatine metabolism
• Rate of production is proportional to skeletal muscle mass
• GFR and plasma creatinine level (in steady-state) are inversely related

 

Glucose

• Freely filtered
• Reabsorbed in promixal tubules
  * By saturable secondary active transport system
  * Normally completely reabsorbed.

Thus,

Glucose excretion is normally zero.

 

NB:

• Theoretical transport maximum (Tm) is about 375mg/min in men and 300mg/min in women
• Should correspond to plasma level of 300mg/dL
  * 375/300 x 100
• But actual renal threshold is about 200mg/dL of arterial blood or 180mg/dL of venous blood
  * Due to splay