Renal plasma clearance Flashcards
Explain the inulin method
-inulin (not insulin)
-an inert polysaccharide
-filters freely through the glomerular membrane
-not absorbed, secreted or metabolised
Explain the relationship between the rate of filtration through glomerular membrane and rate of entry into bladder
Rate of filtration through the glomerular membrane = rate of entry into bladder
What is the equation for rate of inulin filtration
rate of inulin filtration= [Pin] x GFR
What is the equation of Pin x GFR
Pin x GFR = Uin x urine flow rate
What is the rate of entry into bladder
rate of entry into bladder= [Uin] x urine flow rate
What is the equation for GFR
GFR= Urine insulation concentration x urine flow rate x plasma inulin concentration
What is the definition of renal clearance
Renal clearance of a substance is the volume of plasma that is completely cleared (excreted into urine) of the substance by the kidney per unit of time (ml/min)
What are drawbacks of inulin method
- Drawbacks inulin method:
- prolonged infusion
- repeated plasma samples
- difficult routine clinical use
- Use creatinine for clinical GFR measurement
What are advantages and disadvantages for measuring GFR (creatinine)
Advantages:
-an intrinsic inert substance
-released at steady level in plasma from skeletal muscle
-no infusion needed
-freely filtered
-not reabsorbed in the tubule
Disadvantages:
-some secreted into the tubule
-GFR < Ccr = Ucr x V*
Explain the mechanism of creatinine
Trimethoprim competes with Crn for same transporters that secrete Crn from tubular blood into urine —-> increase in serum levels of Crn
What is the equation for GFR
GFR/CCr= UCr x V* PCr
Explain EGFR
eGFR is estimated Glomerular Filtration Rate:
- An equation using blood tests, age, sex, and other information to estimate GFR
- Current equation = CKD-EPI Adults (Chronic Kidney Disease Epidemiology
Collaboration)
A New Equation to Estimate Glomerular Filtration Rate. Ann Intern Med. 2009; 150:604-612. - This isn’t as good as measuring it (i.e. 24h urine collection), but is much
simpler as it requires just one blood test. - Can spot kidney disease earlier than would be possible using just
creatinine measurements
What are the 5 stages of CKD stages
1) GFR* 90+
-normal kidney function but urine findings or structural abnormalities or genetic trait point to kidney disease
-treatment: observation, control of blood pressure
2) GFR* 60-89
-mildly reduced kidney function point to kidney disease
-treatment; observation, control of blood pressure and risk factors
3A/3B) GFR* 45-59 OR 30-44
-severely reduced kidney function
-planning for end stage renal failure
4) GFR* 15-29
-severely reduced kidney function
-planning for end stage renal failure
5) GFR* <15 or on
-very severe, or end stage kidney failure
-treatment choices
What are final notes on EGFR
-it is only an estimate (significant error is possible)
-eGFR is most likely to be inaccurate in people at extremes of body type
-it is not valid on pregnant women or children or patients over the age of 70
Explain the clearance of different substances
1) Substances with clearance= (inulin = GFR):
-approx 125ml/min in adult male and 10% less in females
-e.g. antibiotics ((streptomycin)
2) substances with clearance < inulin (<GFR):
-either not filtered freely
-or reabsorbed from tubule
3) substances with clearance > inulin (>GFR):
-secreted into tubule
Explain what happens when GFR > clearance
1) not freely filtered:
-albumin clearance
-similarly for drugs bound to albumin
2) substances that are reabsorbed:
-filters freely but is usually absent from urine—> completely reabsorbed
Explain what happens when GFR > clearance in other substances
Actively reabsorbed:
-all amino acids
-clearance= 0ml.min-1 unless excess filtered
-pathological conditions
-production of Bence-Jones protein in plasma
-Ca2+, Na+, PO42-, Mg2+
-water soluble vitamins
-passively reabsorbed
Explain what happens when clearance ? GFR and examples
-substances that are secreted:
-filters freely
-secreted actively against electrochemical gradient
Examples:
-endogenous
-weak organic acids and bases, adrenaline, dopamine, steroids
-exogenous :
-penicillin, probenecid, para-aminohippuric acid
Explain renal plasma flow (RPF) and renal blood flow (RBF)
-RPF is the rate at which plasma flows through the kidney
-estimating the RPF through the kidneys allows us to estimate the rate of total blood (RBF) through the kidneys
-blood consists of about 55% plasma and about 45% cellular components
Explain para-aminohippuric acid
-PAH is a weak acidic metabolite of glycine (originally found in horse urine)
-filtered freely and enters glomerular filtrate but large amount still in plasma
-majority is secreted back into proximal convoluted tubule —> excreted into urine
-suitable as a marker to measure renal plasma flow
Explain how PAH secretion happens simply
-active transport occurs in basolateral membrane
-passive transport across luminal membrane into tubule
What happens if PAH is low enough
if plasma (PAH) is low enough- it is virtually completely cleared in a single pass through the kidney
Explain renal filtration fraction
-GFR and RPF can be used to calculate the filtration fraction
-filtration fraction= GFR
GFR is determined from inulin clearance
RPF determined from PAH clearance
What are normal clearance values
1) Glucose:
-0ml/min-1
-completely reabsorbed
2) Inulin:
-125ml/min-1
-not reabsorbed and not secreted
3) PAH:
-625ml/min
-completely secreted
