Renal Chapter 3: Clearance Flashcards
What is renal clearance?
How is rate expressed?
substance is removed from the blood and excreted in urine
volume of plasma per unit time from which all of a substance is removed
substance’s plasma half life (time it takes for plasma concentration to fall to half of its current value) =t1/2
How do you calculate amount cleared and amount in urine? What is the best formula to use?
amount cleared per unit time is the product of volume of plasma cleared per unit time (Cx) and the plasma concentration (Px)
so amount cleared= Cx x Px
(this is plasma before clearance)
amount appearing in urine is the product of urine flow rate (V) and the urine concentration of X (Ux)
amount in urine = V x Ux
(urine after clearance)
(the amount removed from plasma must equal amount appearing in urine)
so Cx x Px = V x Ux
Cx= (V x Ux)/Px
so clearance of substance X is excretion rate divided by plasma concentration
With a concentration of inulin in plasma of 4mg/L and volume of filtered fluid (GFR) =7.5 L/h
what is total inulin filtered?
7.5L/h x 4mg/L = 30mg/h
no reabsoprtion of inulin, no secretion of inulin - so volume of plasma cleared per unit time is the same as GFR
Why is all inulin filtered, excreted? Describe four properties.
filterability -moves into Bowman’s space in same proportion it was filtered
it cannot move in either direction by the paracellular route around the tubular epithelium- tight junctions are too restrictive to permit saccharides of any sort to move through them
no transport mechanisms on either apical or basolateral surface of tubular epithelium to take up inulin
no enzymes (amylases) present in tubular lumen to break down inulin
What substance has a clearance greater than GFR?
para-aminohippurate (PAH)
small (194 Da) water soluble organic anion that is freely filtered and also avidly secreted by the proximal tubule epithelium (via transcellular route) secretion rate is saturable… (so there is a max. rate of PAH secretion into tubule)
How can you measure effective renal plasma flow?
at low plasma concentrations, about 90% of PAH entering the kidney is removed from the plasma and excreted in urine so its clearance is nearly as great as renal plasma flow… so PAH clearance is used to measure renal plasma flow (ERPF) to indicate that its value is slightly less than true renal plasma flow.
How do you get a clearance rate of 0?
What does it mean if clearance is greater than GFR? Less than GFR? Equal to GFR?
all reabsorbed (glucose) or all degraded (insulin)
clearance greater than GFR- net secretion
clearance less than GFR- net re absorption
clearance = GFR, then no net re-absorption of clearance
What is the gold standard for measuring GFR? What are the downsides of using this method? What other methods are available?
gold standard- inulin, but cumbersome bc inulin must be infused, and must be infused at a rate sufficient to keep its plasma concentration constant during the period of urine formation and collection
(if GFR is normal, between 2.5% and 3.5% of plasma inulin is removed every minute and must be replaced by infusion if GFR is to be accurately determined
for routine assessment of GFR in hospitalized patients can use creatinine clearance
Describe creatinine clearance. What is creatinine/why is it used?
creatinine is end product of creatine metabolism and is exported into blood by skeletal muscle continuously
creatinine is freely filtered and not reabsorbed. small amount is secreted by proximal tubule.
(so creatinine in urine represents both a filtered component and secreted component)
Bc of secretion, creatinine clearance is slightly higher than GFR. Secreted fraction is usually 10-20% of what is excreted so measured creatinine clearance overestimates GFR by the same percentage.
How is creatinine clearance measured clinically? What are some errors?
patient’s urine collected for 24 hours.. blood sample is taken sometime during collection period
blood and urine are assayed for creatinine concentration and apply clearance formula to yield creatinine clearance.
additional errors: errors in assays for plasma and urine creatinine concentration or drug infused alteration of creatinine secretion)
If a patient had a very low GFR, how would their measured creatinine clearance be affected?
low GFR, then secreted component is relatively larger fraction of total amount excreted; so creatinine clearance more severely overestimates GFR in patients with a very low GFR than in those w normal GFR values.
Creatinine clearance is a valuable clinical measure of GFR but in practice it is more common to measure plasma creatinine alone and use this as an indicator of GFR. Why is this acceptable?
bc most excreted creatinine gains entry to the tubule by filtration, if we ignore the small amount secreted, there should be an excellent inverse correlation between plasma creatinine concentration and GFR
What would happen to creatinine concentration if an individual’s GFR suddenly decreases by 50% because of blood clot in the renal artery?
(Normal person’s plasma creatinine concentration is 1mg/dL)
person filters only 50% as much creatinine as normal so creatinine excretion is also reduced by 50%.
now in a positive creatinine balance and plasma creatinine rises.
But despite persistant 50% GFR reduction, plasma creatinine does not rise indefinitely; it stabilizes at 2mg/dL (after it has doubled)
Despite persistant 50% GFR reduction, plasma creatinine does not rise indefinitely; it stabilizes at 2mg/dL (after it has doubled). Why?
Give ex with original normal state: filtered creatinine is 1mg/dL x 1800dL/day =1800mg/day
50% reduction in GFR is offset by doubling of plasma creatinine concentration, restoring filtered load of creatinine to normal.
new steady-state
filtered creatinine =2mg/dL x 900dL/day =1800mg/day
person is in balance bc of doubleing of plasma creatinine concentration…creatinine excretion is below normal only transiently until plasma creatinine has increased as much proportionally as GFR has fallen
see graph, screen shot/p 53
What would happen to creatinine concentration in plasma and creatinine excretion if GFR fell to 300dL/day?
(What would new plasma creatinine be?)
creatinine retention would occur until new steady-state, until person filtering 1800mg/day
1800mg/day = Pcr x 300dL/day Pcr= 6mg/dL
(rise in plasma creatinine results directly from fall in GFR)
Rise in plasma creatinine results directly from a fall in GFR. So a single plasma creatinine measurement is a reasonable indicator of GFR.
Why is it not completely accurate?
some creatinine is secreted
no way of knowing exactly when person’s original creatinine was when GFR was normal
creatinine production may not remain completely unchanged
The hospital lab reports that your patient’s renal creatinine clearance is 120 g/day.
This value is
A. Normal
B. Significantly above normal
C. Not an interpretable number as presented
The answer is C. Clearance units are volume per time, not mass per
time.
A substance is known to be cleared from the body both by renal excretion and
by nonrenal mechanisms. Is the renal clearance higher, lower, or the same as the
metabolic clearance rate?
The answer is lower. Metabolic clearance rate includes all routes of elimination; its value is the renal clearance plus any others.
Inulin clearance is measured twice; the first time at a low inulin infusion rate, and
the second time at a higher infusion rate that results in a higher plasma inulin concentration
during the test. Assuming the kidneys behave the same in both cases,
which measurement will yield a higher inulin clearance?
A. The first
B. The second
C. Both measurements are the same.
The answer is C.
Cin = UinV/Pin. When Pin increases, there is no change
in Cin because Uin rises by an identical amount. In other words, the mass of inulin filtered and excreted increases, but the volume of plasma
supplying this inulin (ie, completely cleared of inulin) is unaltered.
The clearance of substance A is less than inulin clearance. Give 3 possible
explanations.
Substance A could be (1) poorly filtered at the glomerulus, (2) taken up and degraded by the tubular epithelium, or (3) reabsorbed and returned
to the blood.
