3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.4. Physiology
                  3.1.4.5. Renal physiology
 3.1.4.5.1. Renal clearance 

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