Renal Physiology - Renal clearance Flashcards
what is renal clearance?
it is the removal of a given substance from the plasma by the kidney
what is renal clearance a function of?
of: filtration (GFR)
Tubular reabsorption
tubular secretion
what does the collective work of filtration (GFR)
Tubular reabsorption and tubular secretion lead to?
urine formation and determines the amount of a specific substance in the urine
what are clearance values?
these provide numerical expressions of how efficient the kidneys excrete various substances
what is the renal clearance rate?
it is defined as the volume of plasma containing being completely cleared of and excreted in the urine per minute
what needs to be done in order to calculate renal clearance rate?
collect urine for known period of time
measure conc of substance(s) in urine + calculate its excretion in the urine per minute
what is the ‘clearance of the substance’?
i.e. the volume of plasma that would have to be cleared completely of the substance to result in the measured urinary excretion can then be calculated
calculating the renal clearance of a filtered only substance gives us?
gives us GFR and an indication of renal health
what criteria do the substances have to meet - the clearance of a substance which meet the criteria will give a measure of GFR?
it is freely filtered at glomerulus
it is not reabsorbed from the filtrate
it is not secreted into the filtrate
it is not metabolised by the tubular cells
it does not interfere w/ kidney function - not toxic
easily measured
IN OTHER WORDS - what criteria do the substances have to meet - the clearance of a substance which meet the criteria will give a measure of GFR?
such a substance enters the tubular filtrate via filtration only and then flows through the tubules and exits in the urine - there should not be any reabsorption or secretion
what is inulin?
a polymer of fructose w/ molecular weight 5.2kDa
NOT produced in body
how can you use inulin?
give to animals - measure what is in urine which is an indicator of what has been filtered so can get measure of GFR
does inulin meet the criteria?
YES
rate filtered (of inulin) =
rate excreted
how must inulin be administered?
intravenously (as continuous rate infusion)
inulin isn’t very clinically useful - what substance is?
creatinine
what is creatinine?
it is the degradation product of creatine phosphate in muscles
what part of the criteria does creatinine not meet?
it doesn’t meet the ‘it is not secreted into the filtrate’ part of the criteria
slight secretion of creatinine means what?
that creatinine enters the filtrate - not only by filtration but also by secretion
meaning that the ‘U’ in the equation is erroneously high
Why is the ‘P’ in the equation also erroneously high?
because the method used for estimation of plasma creatinine conc also detects another compound
two errors in calculation for creatinine?
the two errors (w/ P and U value) cancel each other out so creatinine clearance is commonly used to measure GFR
how else can you measure substances that are normally excreted by the kidneys?
in plasma
what substances can you measure that are normally excreted by the kidneys in plasma (or serum)?
urea (blood urea nitrogen, BUN)
Creatinine
SDMA
what does SDMA stand for?
symmetric dimethylarginine
where is urea reabsorbed?
in PCT and CD
where is urea secreted?
in descending loop of Henle for hyperosmotic gradient
what does the variable concentration of urea depend on?
depends on diet and hydration
how bad does the damage have to be in order to recognise kidney damage with the use of plasma concentrations of urea?
requires significant kidney damage before noticeable effect in plasma concentration
where is creatinine get reabsorbed?
it doesn’t
where is creatinine get secreted?
only small amount secreted into renal tubules
what is the production/degradation ratio for creatinine?
it is stable
when is kidney damage raised relying on the plasma conc of creatinine?
when up to 75% reduction in GFR
SDMA is a … and is produced alongside?
it is a methylated amino acid produced alongside asymmetric dimethylarginine (ADMA)
what is SDMA (alongside ADMA) produced as a biproduct of?
of intranuclear methylation of regulatory proteins and subsequent proteolysis
SDMA is biologically… and excreted by?
Biologically inactive and excreted by the kidneys
what happens to ADMA?
it is metabolised
when is the rise in SDMA detected?
when 25-40% reduction in GFR
how are plasma concentrations of substances used to indicate GFR?
combination of serum creatinine and SDMA used to help stage chronic renal failure
used in conjunction with clinical signs
what other tests are used to detect kidney damage?
urine protein: creatinine (UPC)
what is UPC used to detect?
used to detect protein loss in urine e.g. if glomerular disease is causing destruction of the filtration barrier
what is UPC needed to first rule out?
urinary tract infection
inflammation
haematuria (blood in urine)
not always high in renal disease