Renal Plasma Clearance Flashcards
(31 cards)
What substance is goof to use for GFR?
A substance that is only filtered and is not partially or almost completely reabsorbed - all of what is put in will be filtered out
Describe why inulin can be used to find GFR including what is it and how it passes through the kidney
- An inert polysaccharide that has a molecular weight of 5000
- Filters freely through the glomerular membrane
- Not absorbed - secreted or metabolised
- When inulin is added there will be a [plasma inulin]
- Some of this will continue in the bloodstream but some will pass through the glomerulus and into the tubule
- It is not reabsorbed or secreted so there will be a [urine inulin]
- Hence the rate of filtration through the glomerular membrane = the rate of entry into the bladder
State how to find the rate of inulin filtration and the units for the components of the equation
The rate of inulin filtration = [plasma inulin] x GFR
- [plasma inulin] has the units mg/ml
- GFR has units mg/min
- Hence rate of inulin filtration has the units mg/min
State how to find the rate of entry into the bladder
The rate of entry into the bladder = [urine inulin] x urine flow rate (the urine volume collected/time)
[plasma inulin] x GFR is equal to?
= [urine inulin] x urine flow rate
How do you calculate GFR
GFR (ml/min) = [urine inulin (mg/ml)] x urine flow rate (ml/min) / [plasma inulin (mg/ml)]
What is 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)
Describe how we would calculate the renal clearance of insulin
- The plasma enters the afferent arteriole at a rate of 625 ml/min
- As the rate of flow through the glomerulus is 1/5th the rate it flows through the glomerulus at 125 ml/min
- Inulin is not reabsorbed or secreted so all filtered inulin ends up in the urine
- The clearance is the volume of plasma cleared of the substance in one minute which would be 125ml/min = GFR
How do you find the clearance rate of substance S
(urinary concentration of s x urine flow rate) / plasma concentration of S
What are the drawbacks of using insulin
- Requires prolonged infusion
- Needs to have repeated plasma samples
- It is difficult to use as a routine clinical procedure
What are the advantages and disadvantages of using creatinine
- Advantages of using creatinine -
- It is an intrinsic inert substance
- Released at a steady level in the plasma from skeletal muscle
- No infusion is needed
- Freely filtered
- Not reabsorbed in the tubule
- Disadvantages of using creatinine -
- Some is secreted into the tubule
- GFR is less than the renal clearance rate - has a typical rate of 150ml/min rather than 125ml/min
Describe where creatinine is formed
- Comes from the diet or the liver where it enters the muscles
- It is then metabolised in the muscle into phosphocreatine by creatine kinase and creatine and phosphocreatine then form creatinine
- Creatinine is a waste product that is then excreted in the urine
Why do antibiotics create higher creatinine levels?
- When creatinine is secreted it is by an active mechanism that is by the same transporter than is inhibited by an antibiotic called trimethoprim
- Those on trimethoprim have higher plasma creatinine levels
Relate GFR to renal clearance rate via an equation
GFR = renal clearance rate = [urine creatinine] x urine flow rate / [plasma creatinine]
Show that there is an inverse relationship between plasma clearance rate and plasma creatinine
Plasma clearance rate is proportional to 1/ [plasma creatinine]
Describe what [creatinine] and 1/[creatinine] look like on a graph against GFR
- When [creatinine] is high the % of normal GFR is low (curve downwards)
- When 1/[creatinine] is low the % of normal GFR is low and increases as 1/[creatinine] increases (straight line )
- GFR does decrease naturally with age so this fact must be considered
Describe how GFR can be estimated eGFR, its advantages and disadvantages
- Uses an equation using blood tests, age, sex and other information as an estimation
- Current equation is CKD-EPI adults
It isn’t as good as urine urine samples but is simpler as it needs just 1 blood test - You can spot kidney disease earlier than would be possible only using creatinine to measure
- K= 0.7 for female and 0.9 for male, alpha = -0.329 for females and -0.411 for males
- Weight is not needed as results are normalised to 1.73m squared body surface area
- The test is such that any value above 60ml/min is stated as such and is not given a particular value - the test acknowledges that it is not good above this value
Describe the stages of kidney disease (what the GFR is, the function of the kidney and the treatment)
- 90+ - normal kidney function but urine findings or structural abnormalities or genetic traits point to kidney disease - mildly reduced kidney function and other findings point to kidney disease - treatment with observation, control of blood pressure
- 60-89 - mildly reduced kidney function and other findings point to kidney disease - treatment is observation and control of blood pressure and risk factors
- A (45-59) B (30-44) - moderately reduced kidney function - treatment is observation, control of blood pressure and risk factors
- 15-29 - severely reduced kidney function - planning for end stage renal failure
Less than 15 or on dialysis- very severe or end stage kidney failure - treatment choices
Why is there a significant error in the GFR measurement?
significant error is possible- likely to be inaccurate in people with extreme body types e.g. malnourished, amputees etc and isn’t valid in pregnant women, children or impatiens older than 70 years
State the 3 relationships between clearance and GFR and how the kidney processes these
- Substances with clearance = inulin = GFR - 125ml/min in adult males and 10% less in females- e.g. antibiotics
- Substances with clearance < inulin (<GFR) - either not filtered freely or reabsorbed from tubule
- Substances with clearance > inulin (>GFR) - secreted into tubule
State the 2 types of substances that have a clearance > GFR
- Not freely filtered e.g. albumin clearance = 0ml/min - similarly are drugs bound to albumin e.g. digoxin and warfarin
- Substances that are reabsorbed - filters freely but is usually absent from urine - completely reabsorbed - e.g. glucose clearance = 0ml/min
How is glucose handled by the kidney? - talk about filtration, excretion and reabsorption
- As [plasma glucose] increases the glucose filtration rate increases (GFR x [plasma glucose])
- As [plasma glucose] increases the rate of excretion increases ([urine glucose] x urine flow rate) - does not start from 0 starts from the renal threshold of around 10mM
- As [plasma glucose] increases the reabsorption rate stays constant { (GFR x [plasma glucose]) - ([urine glucose] x urine flow rate) }- this increases till it reaches the transport maximum at which point it will stay constant
Describe glucose clearance on a graph
- On a graph of [plasma] (x axis) against clearance (y axis) glucose starts to increase at the glucose renal threshold and then plateaus
- It plateaus at the point at which GFR - transport maximum (the maximum it could be without reabsorption - the reabsorption)
What are some other substances where clearance < GFR?
- Actively reabsorbed -
- All amino acids - clearance is 0 ml/min unless excess is filtered - pathological conditions e.g. myeloma
- Ca2+, Na+, PO4 2- and Mg2+
- Water soluble vitamins
- Passively reabsorbed -
- Cl-
- Urea
- Some drugs