Renal Plasma Clearance Flashcards
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
Describe what type of substances have a clearance > GFR and give some examples
- Substances that are secreted
- Filter freely but also secreted against the electrochemical gradient
Endogenous - weak organic acids and bases, adrenaline, dopamine, steroids
Exogenous - penicillin, probenecid, para aminohippuric acid
Define renal plasma flow
The rate at which plasma flows through the kidney
What does estimating renal plasma flow allow us to estimate?
Allows us to estimate the rate of total blood flow through the kidneys as blood contains 55% plasma and 45% cellular components
Describe what paraaminohippuric acid is and why it can be used as a marker for renal plasma flow
- This is a weak metabolite of glycine originally found in horses urine
- Filtered freely and enters glomerular filtrate but there is a large amount still in the plasma (4/5ths)
- Majority is secreted back into proximal convoluted tubule - excreted in the urine
- Hence it is a suitable marker to measure renal plasma flow
How is PAH secreted
- Between the epithelial cells of the tubule and the blood capillary there is a Na+/K+ ATPase that pumps 3Na+ ions into the capillary and 2K+ ions into the epithelial cells
- This creates a Na+ gradient so Na+ enters epithelium via a cotransporter than also transports PAH into the epithelial cells
- PAH then passes into the lumen of the tubule via passive movement through a cotransporter that transporters anions into the epithelial cells
Describe PAHs renal plasma flow
- If plasma (PAH) is low enough it is virtually completely cleared in a single pass through the kidney
- Hence the rate at which PAH enters the kidney = the rate at which PAH leaves the kidney in the urine
- Rate of PAH entering kidney = RPF x [plasma PAH]
- Rate of PAH leaving kidney = [urine PAH] x urine flow rate
Hence = RPF = ( [urine PAH] x urine flow rate ) / [plasma PAH]
Describe what filtration fraction is and what is needed to calculate it
Renal filtration fraction -
- GFR and RPf can be used to calculate the filtration fraction
- I.e. the fraction of plasma that is filtered through the glomeruli
Filtration fraction = GFR (the rate at which it is filtered through the glomeruli) / RPF (rate at which all plasma is passing through the kidneys)
- GFR is determined from inulin clearance
- RPF is determined from PAH clearance
