Renal Plasma Clearance Flashcards
List the forces favouring filtration.
Glomerular capillary pressure - usually 60 mmHg
List the forces opposing filtration.
- Hydrostatic pressure in the Bowman’s space - usually 15 mmHg
- Osmotic force of plasma proteins - usually 29 mmHg
Why is the GFR important?
Rapid removal of waste products
How are GFR and plasma volume related?
- GFR is around 180 L/day
- Plasma volume is about 3 L
- Entire plasma can be filtered around 60 times a day
What factors determine GFR?
- Hydrostatic and oncotic pressures across the capillary membranes
- Permeability of the capillary filtration barrier
- Surface area available
Why is GFR important clinically?
Indicates renal failure if too low
How do we measure GFR?
- Using a substance that is freely filtered, but neither reabsorbed nor secreted
- Excretion rate is equal to the rate at which it is filtered
What is the inulin method?
- Inert polysaccharide
- Filters freely through the glomerular membrane.
- Not absorbed, secreted or metabolised.
Using the inulin method, what is the equation for measuring GFR?
GFR = (Uin x V*)/ Pin
GFR is in ml/min, Pin is plasma inulin concentration in mg/ml, Uin is urine inulin concentration in mg/ml and V* is urine flow rate in ml/min.
What is the definition of renal clearance?
Volume of plasma that is completely cleared of the substance by the kidney per unit of time
What is the renal clearance formula?
Cs = (Us x V*) / Ps
Cs is the clearance rate of a substance, Ps is the plasma concentration of the substance, Us is the urinary concentration of the substance and V* is the urinary flow rate.
List some drawbacks of the inulin method.
- Prolonged infusion
- Need repeated plasma samples
- Difficult routine clinical use
What is an alternative instead of inulin for GFR determination?
Creatinine
List some advantages of using the creatinine method for measuring GFR.
- an intrinsic inert substance
- no infusion needed
- freely filtered
- not reabsorbed in the tubule
List some disadvantages of using the creatinine method for measuring GFR.
- some is secreted into the tubule
- causes higher than expected GFR reading
Describe how trimethoprim affects creatinine serum levels.
- Competes with creatinine for the same transporters that secrete creatinine from the tubular blood into the urine. Greater affinity for trimethoprim
- Increases the serum levels of creatinine.
Does trimethoprim influence GFR?
No
Using the creatinine method, what is the equation for measuring GFR?
GFR ≈ Ccr = (Ucr x V*) / Pcr
Ccr ∝ 1/Pcr
How is GFR affected with age?
Declines with age
What factors need to be accounted for when determining GFR?
Age
Gender
Weight
What is eGFR?
estimated Glomerular Filtration Rate
Why is eGFR used?
Simple - only uses a single blood test
What are some problems faced when using eGFR?
- Only an estimate -significant error is possible.
- eGFR is most likely to be inaccurate in people at extremes of the body (eg. malnourished, amputees, etc.).
- Not valid for pregnant women, patients older than 70 years old or children.
Describe what happens when GFR = 90+, and the treatment.
- Normal kidney function
- Urine, findings, structural abnormalities or genetic traits point to kidney disease.
TREATMENT: observation, control of blood pressure.
Describe what happens when GFR = 60-89, and the treatment.
Mildly reduced kidney function; this and other findings point to kidney disease.
TREATMENT: observation, control of blood pressure and risk factors.
Describe what happens when GFR = 45-59/ GFR = 30-44 and the treatment.
Moderately reduced kidney function.
TREATMENT: observation, control of blood pressure and risk factors.
Describe what happens when GFR = 15-29 and the treatment.
Severely reduced kidney function.
TREATMENT: planning for end-stage renal failure.
Describe what happens when GFR<15/on dialysis, and the treatment.
Severe or end-stage kidney failure
TREATMENT: treatment choices.
Compare clearance to inulin.
By comparing the clearance of a substance to inulin (and in effect, GFR) tell a lot about the renal handling of that substance.
What is the identity of a substance with clearance=inulin?
Antibiotics e.g streptomycin
What happens to a substance with clearance < inulin?
Not filtered freely, or reabsorbed from the tubule
What happens to a substance with clearance > inulin?
Secreted into the tubule.
What does it tell you about a substance when the clearance < GFR? PART 1
Substance is not freely filtered:
- Albumin clearance is 0 ml/min. This is similar to drugs bound to albumins, such as digoxin and warfarin.
What does it tell you about a substance when the clearance < GFR? PART 2
Substance is reabsorbed.:
- Filters freely but usually absent from the urine as it is completely reabsorbed. For example, the glucose clearance is also 0 ml/min.
Describe the glucose handling of the kidney.
15 mM is the renal threshold.
- Above this threshold, glucose starts to appear in the urine, and then the reabsorption line falls short of the filtration line.
What occurs when reabsorption line plateaus?
- Plateaus at 22 mM.
- Transport Maximum (Tm) for glucose ie. the rate at which the carrier mechanism is fully saturated.
List some substances that are actively reabsorbed.
- amino acids
- Ca2+, Na+, PO4 2-, Mg2+
- water-soluble vitamins
List some substances that are passively reabsorbed.
Cl-
urea
some important drugs
What is the main difference between actively reabsorbed and passively reabsorbed substances?
Substances that are passively reabsorbed DON’T display Tm.
Why do passively reabsorbed substances not display Tm?
Rate of transport is determined by the other factors (eg. electrochemical gradient, permeability, etc.).
How does glomerular filtrate help form a concentration gradient for solutes?
- Glomerular filtrate flows down the tubule
- Water is reabsorbed
- Solutes are concentrated, providing a concentration gradient down which they diffuse.
What type of substances can diffuse across the tubule wall?
Lipid-soluble substances
What is the importance of only lipid-soluble substances being able to diffuse across the tubule wall?
- Lipophilic drugs tend to return to the bloodstream
- Hydrophilic drugs are lost in the urine.
What can we tell about a substance that has its clearance > GFR?
We can tell that it is a substance that is secreted.
- it filters freely
- it is secreted actively against the electrochemical gradient
Give example of endogenous substances.
- Weak organic acids and bases
- Adrenaline
- Dopamine
- Steroids
Give examples of exogenous substances.
- Penicillin
- Para-amino hippuric acid (PAH)
Describe RPF (renal plasma flow)
- Rate at which plasma flows through the kidney.
Describe RBF (renal blood flow)
Blood consists of about 55% plasma and about 45% cellular components (mostly RBCs).
What does an estimation of RPF allow?
Allows to estimate the rate of total blood flow through the kidneys.
Describe PAH (para-aminohippurate acid).
- Weak acid metabolite
- Filtered freely and enters the glomerular filtrate.
- Large amount in the plasma.
What makes PAH suitable to measure renal plasma flow?
Majority of it is secreted back into the proximal convoluted tubule and excreted into the urine.
With PAH secretion, describe the different transport mechanisms across the different membranes.
- Active transport occurs in the basolateral membrane.
- Passive transport occurs across the luminal membrane into the tubule.
With PAH, what is the equation for RPF?
Amount of PAH delivered to the kidneys in the blood is equal to the amount excreted in the urine. So:
RPF = (Upah x V*) / [PAH]
How do we calculate the renal filtration fraction?
Filtration Fraction = GFR/RPF
GFR is determined from inulin clearance, while RPF is determined from PAH clearance.
What happens if PAH is below the Tm?
→ It is cleared in a single pass
Why does the concentration of penicillin fall rapidly when injected and how is this counteracted?
→ Renal tubular cells actively secrete it into the urine
→ Given with probenecid which competes for the same transport mechanism
Why does the clearance rate of glucose never reach the rate of inulin?
→ the transporters are still working unless they are completely blocked
Why does glucose start appearing in the urine before 20mM?
→ Each nephron has a slightly different transport maximum
→ Some nephrons will start excreting glucose earlier than others
What happens to the glucose after > 20mM?
→ All the transporters are saturated
→ Glucose reabsorption plateaus
→ Glycosuria
What happens to the glucose < 20mM?
→ All the glucose that filters through is reabsorbed by the Na+/glucose co-transporter
What is the equation for calculating glucose reabsorption?
→ [(GFR x Pglucose) - ( U glucose x V)]
What is the equation for calculating glucose excretion?
→ Uglucose (urine glucose concentration) x V (urine flow rate)
What is the equation for calculating glucose filtration?
→ GFR x Plasma glucose
How is glucose handling by the kidney investigated?
→ infuse glucose and inulin together
→ calculate GFR using inulin
→ calculate the glucose filtration rate (GFR x plasma glucose concentration)
Why are there differences in GFR?
→ age
→ gender
→ muscle mass
How is creatine made?
→ Taken in the diet
→ found in the liver
What is creatine metabolized by?
Phosphocreatine
What can creatine and phosphocreatine be metabolized into?
Creatinine
What is the urinary excretion rate?
GFR - reabsorption rate + secretion rate
What is proteinuria a sign of?
Renal/ urinary tract disease
