1. The Renal System

2. Objectives To define clearance
To describe how to measure GFR using the clearance of Inulin and Creatinine
To describe how to measure renal blood flow using the clearance of Para-aminohippurate

3. Measurement of Glomerular Filtration Rate (GFR)

4. Clearance Cx = Ux X Vml/min px Cx = clearance of substance x
Clearance is the volume of plasma from which a substance is completely cleared to be excreted in urine per unit time.
Clearance of substance x is calculated as follows:
Cx = Ux X Vml/min px
Cx = clearance of substance x
Ux = concentration of substance x in urine
V = urine volume per unit time (urine flow rate)
Px = concentration of substance x in plasma

5. Clearance Clearance is used to:
Measure glomerular filtration rate (GFR)
Measure Renal Plasma Flow (RPF)
Assess tubular transport mechanism
Assess GFR & RPF in patients

6. Characteristics of a substance suitable for measuring the GFR by determining its clearance:
Freely filtered (i.e. not bound to protein in plasma).
Not reabsorbed by tubules
Not secreted by tubules
Not metabolised
Not stored
Not toxic
Has no effect on filtration rate
Preferably easy to measure in plasma and urine

7. Inulin Clearance Amount filtered cortex
medulla
Inulin Clearance
Amount filtered
Amount filtered = GFR x Plasma concentration
Amount filtered = GFR x Px
Amount excreted = Urinary concentration x Urine volume
Amount excreted
Amount excreted = Ux x V

8. Measurement of GFR GFR x Pc = Uc x Vml/min GFR = Uc x V Pc
amount filtered = amount excreted
GFR x Pc = Uc x Vml/min
GFR = Uc x V
ml/ min Pc

9. Fructose polymer, molecular weight 5200.
Measurement of GFR
Substances used to measure GFR:
Inulin:
Fructose polymer, molecular weight 5200.
Procedure:
an intravenous load of inulin is administered followed by sustained infusion of inulin until plasma level is constant.
urine is collected for a timed period to get urine flow rate and urinary concentration of inulin.

10. Measurement of GFR Creatinine
product of metabolism of creatine phosphate in muscles.
plasma concentration =< 1 mg/dL.
Procedure:
urine is collected for 24 hours.
a sample of plasma to measure creatinine is obtained at mid-time collection of urine.

11. Renal Blood Flow Measurement (RBF)
The substance used is Para amino hippurate (PAH).
Characteristics:
easily filtered
not reabsorbed
highly secreted
not metabolized
not synthesised
not stored

14. Renal Blood Flow Measurement RBF
Fick’s equation:
RBF = Qx
RAx-RVx
Qx = rate at which substance x consumed
RAx concentration of x in renal artery
RVx = concentration of x in renal vein
If we apply this equation to plasma then
RPF = Qx
PRAX -PRVX

15. Renal Blood Flow Measurement RBF
If substance x is not metabolised or synthesised or stored, then rate of consumption by the kidney can be equated to the rate of its excretion.
(Ux X V)
If substance x is not metabolized by other tissues, then
PRAx=Px
If substance x is highly secreted, then
PRVx =0

16. Renal Blood Flow Measurement RBF
Then
RPF = Ux X V Px
Renal vein plasma concentration of PAH is not zero as 10-15% is not cleared
PAH clearance=effective renal plasma flow ( ERPF)
RPF = ERPF X 100 90
RBF = RPF X
(100-Hct)
Hct = heamatocrit
RPF = 625 ml/min

18. Objectives
To describe the factors that modify GFR

19. Factors Affecting GFR
1. changes in renal blood flow

20. Factors Affecting GFR changes in systemic blood pressure
2. changes in glomerular capillary hydrostatic pressure
changes in systemic blood pressure
afferent or efferent arteriolar constriction

21. Factors Affecting GFR a. ureteric obstruction
3. changes in hydrostatic pressure in Bowman’s capsule
a. ureteric obstruction
b. Edema of kidney inside tight renal capsule

22. Factors Affecting GFR
4. Changes in capillaries oncotic pressure.

23. Factors Affecting GFR
5. increased permeability of glomerular filtration membrane:
Various diseases

24. Factors Affecting GFR
6. decrease in total area of glomerular capillary bed
a. Diseases that destroy glomeruli with or without destruction of tubules
b. Partial nephrectomy.

25. Factors Affecting GFR Summary 1. changes in renal blood flow
2. changes in glomerular capillary hydrostatic pressure
a. changes in systemic blood pressure
b. afferent or efferent arteriolar constriction
3. changes in hydrostatic pressure in Bowman’s capsule
ureteral obstruction
Edema of kidney inside tight renal capsule

26. Factors Affecting GFR Summary
4. Changes In capillaries Oncotic pressure.
5. increased permeability of Glomerular. filtration membrane: various diseases.
6. decrease in total area of Glomerular capillary bed.
a. Diseases that destroy Glomeruli with or without destruction of tubules
b. Partial nephrectomy.