Transcript L3- Renal clearance.ppt

RENAL CLEARANCE
Renal Clearance
Definition:
Is the volume of plasma completely cleared
of a substance by the kidneys per unit time.
The higher the renal clearance, the more
plasma that is cleared of the substance.
Unit: ml/min
Nephron Excretion & Clearance
Inulin
A plant product that
is filtered but not
reabsorbed or
secreted
Used to
determine
clearance rate
and therefore
nephron function
Nephron
Excretion & Clearance
The relationship between clearance and excretion using a few examples
Nephron
Excretion & Clearance
Equation for renal clearance
Cx = Ux x V
Px
Where x = substance
Cx = clearance of substance
Ux = urine concentration of substance
Px = plasma concentration of substance
V = urine flow rate (ml/min)
Amount of substance excreted = (filtered –
reabsorbed + secreted)
Ux V = GFR x Px ± Tx
Comparison of clearance of a substance
with clearance of inulin
1) = inulin clearance; only filtered not reabsorbed
or secreted
2) < inulin clearance; reabsorbed by nephron
tubules
3) > inulin clearance; secreted by nephron tubules
Examples: clearance of known substances
Glucose (0)
Urea (40 ml/min)
Inulin (125 ml/min)
PAH (585 ml/min)
100
200
300 400
500 600
Clearance (ml/min)
Application of renal clearance
in kidney function
 Inulin clearance can be used to estimate GFR
(by calculation)
 PAH clearance can be used to estimate renal
plasma flow
 Measurement of filtration fraction = GFR / RPF
 Measurement of creatinine clearance
Inulin clearance
If a substance is freely filtered and not
reabsorbed or secreted  rate of excretion in
urine is equal to rate of substance filtered by
kidney. Thus,
GFR x PS = US x V
GFR therefore, can be calculated as follows:
GFR = Us x V = Cs
Ps
Inulin, a polysaccharide molecule with MW of
5200, fits these criteria.
INULIN CLEARANCE
GFR = Cin = 125ml/min
CREATININE CLEARANCE
Ccr = Ucr x V
Pcr
Where Ccr = creatinine clearance
Ucr = urine concentration of creatinine
Pcr = plasma concentration of creatinine
V = urine flow rate (ml/min)
Creatinine clearance overestimate GFR by 10-20%
due to creatinine secretion in very small amounts.
Blood urea and creatinine will not be raised above
normal range until 60% of total kidney function is
lost.
Hence, the more accurate GFR or creatinine
clearance is measured whenever renal disease is
suspected or careful dosing of nephrotic drug is
required.
Plasma creatinine:
(Normal plasma creatinine in daults = 0.6 – 1.2 mg/dl)
Plasma creatinine (mg/dl)
16
Index of GFR
12
8
4
0
0
45
90
135
180
Glomerular filtration rate (L/day)
Relationship between serum creatinine
and renal function
Plasma creatinine (mg/dL)
2.3
4.5
6.8
9.0 11.3
120
13.6
Normal
GFR (mL/min)
100
Reduced reserve
80
Renal impairment
60
End-stage
renal disease
40
20
200
400 600
800 1000
Plasma creatinine (µmol/L)
1200
Para-aminohippuric acid (PAH) clearance
If a substance is completely cleared from
plasma  clearance rate is equal to total
renal plasma flow  amount delivered to
kidneys is equal to amount excreted. Thus,
RPF = UPAH x V = CPAH
PPAH
Renal Blood Flow
Resting condition (adult) receive
1.2 L/min (25% of CO)
Measurement of RBF
a) Electromagnetic flow meters
b) Fick’s principle
Fick Principle
• Amount taken up by an organ (kidney) per unit of
time divided by the arterio-venous difference of the
substance = plasma flow
• RPF = amount of substance excreted divided by the
renal arterio-venous difference.
RPF =
UPAH x V
RAPAH – RVPAH
RVPAH = 0,
RPF is described as effective renal plasma flow
(ERPF).
Effective RPF (ERPF)
Effective RPF = UPAH V
PPAH
Where:
Effective RPF = effective renal plasma flow (ml/min)
UPAH = urine concentration of PAH (mg/ml)
V = urine flow rate (ml/min)
PPAH = plasma concentration of PAH (mg/ml)
CPAH = clearance of PAH (ml/min)
Effective RPF = UPAH x V
PPAH
= 14 mg/ml x 0.9 ml/min
0.02 mg/ml
= 630 ml/min
Actual RPF =
ERPF
Extraction ratio
= 630 / 0.9 = 700 ml/min
The clearance of PAHA reflect only RPF to portions of the kidney
that deal with urine formation, and thus underestimate actual
RPF by about 10%.
The renal extraction ratio of PAH = 0.92
Measuring renal blood flow (RBF)
RBF is calculated from RPF and the
hematocrit (PCV). Formula is as follows:
RBF =
RPF
1 – Hct
RBF = 700
0.55
= 1273 ml/min
Hematocrit (PCV) = 0.45
Where:
RBF = renal blood flow (ml/min)
RPF = renal plasma flow (ml/min)
PCV = hematocrit
Glomerular
capillary
Substance
X
Substance
Y
Substance
Z
Bowman’s
space
Urine
Urine
Urine
Renal handling of hypothetical substance X, Y, Z.
X, filtered & secreted not reabsorbed
Y, filtered, fraction reabsorbed
Z, filtered, completely reabsorbed