Dr. Amal Mahmoud SaeedDept. Of Physiology, Faculty of MedicineUniversity of Khartoum Lecture 4

ObjectivesTo define clearance To describe how to measure GFR using the

clearance of Inulin and CreatinineTo describe how to measure renal blood flow

using the clearance of Para-aminohippurate

Dr. Amal Mahmoud SaeedDept. Of Physiology, Faculty of MedicineUniversity of Khartoum Lecture 4

ClearanceClearance 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 = 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

Cx = Ux X Vml/min

px

Clearance

Measure glomerular filtration rate (GFR)

Measure Renal Plasma Flow (RPF)

Assess tubular transport mechanism

Assess GFR & RPF in patients

Clearance is used to:

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 tubulesNot secreted by tubulesNot metabolised Not stored Not toxicHas no effect on filtration ratePreferably easy to measure in plasma and

urine

Inulin ClearanceAmount filtered Amount filtered

Amount excretedAmount excreted

cort

exco

rtex

med

ulla

med

ulla

Amount filtered = GFR x Plasma concentration

Amount excreted = Urinary concentration x Urine volume

Amount filtered = GFR x Px

Amount excreted = Ux x V

Measurement of GFR

amount filtered = amount excreted GFR x Pc = Uc x Vml/min

GFR = Uc x VPc

ml/ min

Measurement of GFR

• 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.

1.Inulin:Procedure:

Substances used to measure GFR:

Fructose polymer, molecular weight 5200.

Measurement of GFR product of metabolism of creatine

phosphate in muscles. plasma concentration =< 1 mg/dL.

2.Creatinine

urine is collected for 24 hours.

a sample of plasma to measure creatinine is obtained at mid-time collection of urine.

Procedure:

Renal Blood Flow Measurement(RBF)

The substance used is Para amino hippurate (PAH).

Characteristics: easily filtered not reabsorbed highly secretednot metabolizednot synthesisednot stored

Renal Blood Flow Measurement RBF

RPF = Qx

RBF = Qx

Fick’s equation:

RAx-RVxQx = rate at which substance x

consumedRAx concentration of x in renal arteryRVx = concentration of x in renal veinIf we apply this equation to plasma then

PRAX -PRVX

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

Renal Blood Flow Measurement RBF

(100-Hct)

RBF = RPF X 100

Then

Renal vein plasma concentration of PAH is not zero as 10-15% is not cleared

PAH clearance=effective renal plasma flow ( ERPF)

RPF = Ux X V

Px

RPF = ERPF X 100 90

Hct = heamatocrit

RPF = 625 ml/min

To describe the factors that modify GFR

Factors Affecting GFR1. changes in renal blood flow

Factors Affecting GFR2. changes in glomerular capillary

hydrostatic pressurea. changes in systemic blood pressureb. afferent or efferent arteriolar

constriction

Factors Affecting GFR3. changes in hydrostatic pressure in

Bowman’s capsule

a. ureteric obstructionb. Edema of kidney inside tight renal

capsule

Factors Affecting GFR4. Changes in capillaries oncotic

pressure.

Factors Affecting GFR5. increased permeability of

glomerular filtration membrane:

Various diseases

Factors Affecting GFR6. decrease in total area of glomerular

capillary bed

a. Diseases that destroy glomeruli with or without destruction of tubules

b. Partial nephrectomy.

Factors Affecting GFR1. changes in renal blood flow2. changes in glomerular capillary

hydrostatic pressurea. changes in systemic blood pressureb. afferent or efferent arteriolar constriction

3. changes in hydrostatic pressure in Bowman’s capsule

a. ureteral obstruction b. Edema of kidney inside tight renal capsule

Summary

Factors Affecting GFRSummary

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.

4. Changes In capillaries Oncotic pressure.