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Renal Clearance
Clearance
20 20 20 20 20 20 20 20 20 20
4 4 4 4 4 4 4 4 4 4
40
1 2 3 4 5 6 7 8 9 10
20 20 20 20 20 20 20 20 2020
4 4 4 4 4 4 4 4 4 4
40
Was any of the carriages completely cleared? No
But can we say that it is as if some carriages were completely cleared?
Yes
If so, how many carriages were completely cleared? 2
20 20 20 20 20 20 20 20 20 20
4 4 4 4 4 4 4 4 4 4
40
Clearance of the train is 2 carriages / station
Remember –• It is not real (it is only as if)• It is related to the train (not the number of passengers)
20 20 20 20 20 20 20 20 20 20
4 4 4 4 4 4 4 4 4 4
40Clearance is -
• Number of carriages of the train cleared of passengers
• The minimum number of carriages needed to supply the number of passengers getting off at the station
OR
• The number of carriages that contained the number of passengers getting off the train
20 20 20 20 20 20 20 20 20 20
4 4 4 4 4 4 4 4 4 4
40
Calculation of clearance -
number of passengers going out of the station number of passengers in each carriage
Apply to plasma and kidney –
Kidney
Solute X excreted
Plasma comes into kidney withmore solute X
Plasma goes out of the kidney withless solute X
Apply to plasma and kidney –
Kidney
Excretion of the solute X
Plasma comes into kidney withmore solute X
Plasma goes out of the kidney withless solute X
Clearance of the solute X =Amount of solute X excreted
Concentration of solute X in plasma
Renal clearance is taken as PER MINUTE
Renal Clearance of a substance is -
• Volume of plasma cleared of the substance by the kidney in one minute
• The minimum volume of plasma needed to supply the amount of substance excreted by the kidney in one minute
OR
• The volume of plasma that contained the amount of substance excreted by the kidney in one minute
Renal clearance of a substance
Total substance excreted in 1 minuteConcentration of substance in plasma
Conc. of substance in urine x Vol. of urine excreted in 1 min
Concentration of substance in plasma
U x V
P
U – concentration of the substance in urine
V – volume of urine produced in 1 minute
P – concentration of the substance in plasma
Unit of renal clearance
U x V P
U – concentration of the substance in urine – mmol/ml
V – volume of urine produced in 1 minute – ml/min
P – concentration of the substance in plasma – mmol/ml
mmol/ml x ml/min mmol/min mmol/ml mmol/ml
Unit of renal clearance is ml/min
= ml/min=
Warning: when performing the calculation make sure that units of U, V and P are similar!
Renal Clearance of a substance - determination
U x V P
U – concentration of the substance in urine – collect urine and measure the concentration
V – volume of urine produced in 1 minute – collect urine for 24 hours and calculate urine output per minute; more accurate asthe output varies throughout the day
P – concentration of the substance in plasma – collect blood during those 24 hours and measure the concentration
Significance of clearance
Measurement of clearance can be used to
determine
1.Glomerular filtration rate – thereby assessing glomerular function
2.Renal plasma/blood flow – not routinely performed
Significance of clearance
1. Glomerular filtration rate – the clearance of a substance freely filtered at the glomerulus but not reabsorbed or secreted in the tubules is the value of GFR
2. Renal plasma/blood flow – the clearance of a substance filtered at the glomerulus and completely secreted by the tubules is the same as renal plasma flow
Significance of clearance
Consider a substance handled by the kidney in the following manner -
1. Freely filtered at glomerulus
2. Completely secreted by tubules
The amount of substanceexcreted comes from the entire plasma flowing through the kidney
Significance of clearance
1. Freely filtered at glomerulus
2. Completely secreted by tubules
The amount of substanceexcreted comes from the entire plasma flowing through the kidney
Calculate the clearance of the substanceU x V P= total plasma flow through the kidney
Significance of PAH clearance
Para amino hippuric acid (PAH) has these characteristics (at low concentrations)
Clearance of PAH = Renal plasma flow
Total plasma flow? No, some blood may bypass the nephrons
Clearance of PAH = Effective renal plasma flow
Total renal plasma flow is about 5 -10% more than effective renal plasma flow
Significance of PAH clearance
If plasma flow is known, blood flow can be calculatedFor this haematocrit needs to be known
clearance of PAH
= Effective Renal blood flow
For example: if PAH clearance is 600ml/min, and haematocrit 40%,
600 / (1 - 40%)Effective Renal blood flow = =600 x 100 60
1 - haematocrit
Significance of clearance
A substance handled by the kidney in the following manner-
1.Freely filtered at glomerulus
2.Not absorbed or secreted by tubules
The amount of substanceexcreted comes entirelyfrom the glomerular filtrate
The amount of substance excreted in 1 minute will come from the glomerular filtrate formed in 1 minute (GFR)
Significance of clearance
A substance handled by the kidney in the following manner-
Clearance of the substance when calculated will give the volume of plasma that contains the amount of substance excreted in 1 minute
Freely filtered at glomerulus
Not absorbed or secreted by tubules
The amount of substanceexcreted comes entirely from the glomerular filtrate
Significance of clearance
The substance excreted comes entirely from the glomerular filtrate
Comes from the glomerular filtrate in 1 minute (GFR)=
the amount of substance
excreted in 1 minute
comes from volume of plasma cleared of the substance in 1 minute (Renal clearance)
=
Clearance as a measure of GFR
The clearance of a substance freely filtered at the glomerulus and not reabsorbed or secreted will be the same as the GFR
Measurement of GFR
Properties of an ideal substance whose clearance mat be determined to measure GFR –
• Freely filtered at the glomerulus• Not reabsorbed by the tubules• Not secreted by the tubules• Not metabolised by the nephron• Not toxic to the body• Does not affect renal function, particularly
glomerular function• Easily measured in the plasma and urine• Found in the body
Clearance as a measure of GFR
The clearance of a substance freely filtered at the glomerulus and not reabsorbed or secreted will be the same as the GFR
The best example of such a substance is INULINInulin clearance, therefore, is the same value as GFR
Measurement of GFR
Inulin as an ideal substance for measuring GFR –
Freely filtered at the glomerulus Not reabsorbed by the tubules Not secreted by the tubules Not metabolised by the nephron Not toxic to the body Does not affect renal function, particularly
glomerular function Easily measured in the plasma and urine Found in the body
Measurement of GFR
Inulin as an ideal substance for measuring GFR –
Found in the body
As inulin is not found in the body it needs to be infused –Associated with risks and restrictions for the person
Alternate substances for measurement of GFR
Creatinine for measuring GFR –(source of creatinine : muscles)
Found in the body
Has a major advantage over inulin as no infusion is necessary
However –Creatinine is secreted in small amounts – tends to
overestimate GFRThe method of measuring serum creatinine gives a
falsely higher value (slight) – tends to underestimate GFR
Creatinine clearance
Commonly performed clearance estimationA good indicator of glomerular function
Parameters measured –• Serum creatinine concentration• 24-hour urine volume• Urine creatinine concentration
Clearance ratio
If the clearance of a substance is :
1. Less than creatinine clearanceReabsorption occurs? Secretion
2. More than creatinine clearanceSecretion occurs? Reabsorption
Serum creatinine
Could serum creatinine be a substitute for creatinine clearance?
Measuring serum creatinine is much easier than determining creatinine clearance
Reasoning may be –? if GFR decreases creatinine excretion decreases? then serum creatinine level increases? Increasing serum creatinine will indicate decreasing GFR
Is this really so?
GFR and plasma creatinine
When GFR falls, plasma creatinine increases but not proportionately – the relationship is not linear
When GFR falls from normal levels
• At lower levels of GFR even small decreases in GFR cause large increases in plasma creatinine
• The plasma creatinine increases
slowly initially
GFR and plasma creatinine
1. A high serum creatinine suggests a low GFR
2. A normal serum creatinine is not proof of normal GFR
Serum creatinine is also dependent on a persons muscle mass
A high serum creatinine suggests a low GFR because there are no other significant factors that change the serum creatinine
Renal Clearance
• Clearance is a concept – not a real value• It refers to plasma - unit : ml/min• It can be determined for any substance excreted
in the urine• Parameters needed for calculation are plasma
concentration, urine concentration and urine flow rate
• The clearance of certain substances are determined as indicators of renal function
• Blood levels of some substances excreted in urine are sometimes used as indicators of glomerular function
• But blood levels do not change proportionately with changes in GFR
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