Renal Plasma Clearance Flashcards
1st step in urine formation begins with glomerular filtration -> what is glomerular filtrate?
what is in it? what is not in it?
what is routinely tested on wards? what is this a sign of?
• Glomerular filtrate = same composition as plasma except:
o Devoid of cellular elements like RBC
o Essentially protein-free
o Hence, urine is routinely tested on wards for protein (proteinuria).
o Proteinuria is a sign of renal/urinary tract disease (>0.5g/day OR ≥250mg/L on test-strip)
Glomerular Filtration Rate (GFR)
what is it and what is it not?
Glomerular Filtration Rate (GFR) is how much filtrate is removed from blood each minute NOT how much blood passes through glomerulus each minute
Control of GFR
driving force?
opposing forces?
net effect?
what determines the filtration across the capillaries?
Favouring filtration:
Glomerular capillary pressure (PGC) = 60mmHg
Opposing filtration:
Hydrostatic pressure in Bowman’s space (PBS) = 15mmHg
Osmotic force of plasma proteins (ΠGC) = 29mmHg
PGC – PBS – ΠGC = 16mmHg (net filtration pressure)
Filtration across the capillaries is determined by opposing forces.
Rate of Urine Formation
how much is filtered through?
what determines the rate at which different substances excreted into urine?
how much is filtered through if 625ml goes to kidney?
if a substance s is filtered in kidney and is not secreted or reabsorved, how much is cleared per min?
20% is filtered through and then the remaining substance is excreted. Of that 20% it may be secreted or reabsorbed.
The rate at which different substances excreted into urine is the sum of 3 renal processes:
-> The rate at which it is filtered - it’s reabsorption rate + the rate at which it is secreted from the peritubular capillary blood into the tubule
therefore urinary excretion rate = GFR - reabsorption rate + secretion rate
Only 20% of plasma flowing through kidneys is filtered through glomerular capillaries. Hence every minute ~625ml of plasma goes to the kidney.
This is renal plasma flow, of the 625ml/min of plasma that goes to the glomerulus, 125ml/min are filtered.
Of this almost all water is reabsorbed and put back into blood. So, for a substance (S) that is in plasma and freely filtered in Bowman’s capsule and is not reabsorbed/secreted, all the (S) that is in filtered plasma will be cleared i.e. 125ml in 1min, but the other 500ml which is NOT filtered keeps it’s (S) as it cannot get into urine.
Why is GFR important?
if GFR is 180/L and plasma vol is 3L, hiow many times filtered?
What determines GFR? (2)
what is a clincial indicator of unctioning of nephrons (renal function)?
how may these processes chnage if there is excess Na in the body?
- GFR contributes to rapid removal of waste products
- GFR is ~ 180L/day & plasma volume ~ 3L -> Entire plasma can be filtered ~ 60x/day
• GFR determined by combination of factors:
o Hydrostatic* and oncotic pressures across capillary membranes
o Permeability of capillary filtration barrier & surface area available
Change in any of these factors will change GFR. Hence GFR important clinical indicator of functioning of nephrons (renal function)
Each of the processes i.e. GFR, tubular reabsorption and tubular secretion are regulated according to needs of the body.
• E.g. if there’s excess Na in body then the rate at which Na filtered increased and the rate at which it is reabsorbed is decreased resulting in increased urinary excretion of Na
- High GFR allows kidneys to rapidly remove waste products that depend primarily on glomerular filtration for their excretion
- Kidney can precisely & rapidly control volume and composition of body fluids
Measuring GFR
how is it measured?
what are the conditions when measuring this?
GFR is not measured directly but by measurement of the excretion of a marker substance. Which of these substances do you think could be used to measure GFR?
- Substance A: freely filtered but neither reabsorbed or secreted. Hence, it’s excretion rate is equal to the rate at which filtered (e.g. creatinine)
- Substance B: freely filtered but partly reabsorbed from tubules back into blood. Hence rate of urinary excretion is less than rate of filtration at glomerular capillaries (e.g. Many electrolytes in body) -> Less than actual GFR
- Substance C: freely filtered but NOT excreted into urine because all filtered substance reabsorbed from tubule back into blood (e.g. glucose and amino acids) -> 0
- Substance D: freely filtered but NOT reabsorbed and additional quantities secreted from peritubular capillaries into renal tubules (e.g. organic acids & bases) -> More than actual GFR
- Substance A is perfect since it is freely filtered and secreted as well as other additional quantities not being secreted.
Inulin Method
why is this the gold standard?
- An inert polysaccharide, MW ~5,000
- Filters freely through the glomerular membrane
- Not absorbed, secreted or metabolised
- Gold standard for measuring GFR but NOT used clinically
Inulin & GFR
How do we get inulin in the body?
How does the plasma inulin become stable?
What do we do once inulin levels become stable?
Concentration of inulin in plasma vs urine
How do you calculate the urine flow rate?
rate of filtration vs rate of entering bladder
Since we do not make inulin we have to infuse it in steady iv till its plasma level (Pin) becomes stable. Whilst this continues then timed urine sample is collected, analysis of this gives Uin and V
The plasma inulin concentration becomes stable when the inulin infusion rate equals the inulin excretion rate.
When plasma inulin concentration has become stable urine is collected over timed intervals and a blood sample is obtained at the mid-point of each urine collection period. The plasma and urine inulin concentrations and the urine volume collected for each period is measured.
Inulin has same concentration in glomerular filtrate as in plasma and because it’s NOT reabsorbed/secreted it has the same concentration in urine.
V* = volume/collection time.
The urine flow rate, V, is calculated by dividing the urine volume collected by the duration in minutes of the collection period.
So, the load of inulin filtering from the plasma into Bowman’s Capsule is over 1min is Pin x GFR
As the filtrate advances from the Bowman’s Capsule to the tubule neither reabsorbs nor secretes inulin, hence the rate at which the inulin arrives at the bladder is identical with the rate at which it filters through the glomerular membrane.
So, the rate at which inulin enters the bladder is Uin x urine flow(V)
Since the rate at which it filters through the membrane is identical to the rate at which it enters into bladder we can write the equation as such.
Pin x GFR = Uin x V*
GFR = Uin x V* / Pin
Where:
GFR = glomerular filtration rate; ml.min-1
Pin = plasma inulin concentration; mg.ml-1
Uin = urine inulin concentration; mg.ml-1
V* = urine flow rate; ml.min-1
COMES UP IN EXAMS LEARN!!!
Renal Clearance - definition
Renal clearance of a substance is the volume of plasma that is completely cleared of the substance by the kidney per unit of time, (in other words excreted in urine each minute) (expressed in ml/min)
Renal Clearance - in relation to inulin
what is special about inulin? what does this mean and how does it help us work out GFR?
use the 625ml example to explain this
what will clincians measure?
Inulin is freely filtered by the glomerulus and is neither reabsorbed or secreted.
Therefore, all the I that is filtered will end up in the urine, no more (as I is not secreted), no less (as I is not reabsorbed).
Thus, all the plasma that gets filtered is cleared of I (that is, all the I in the filtrate gets excreted) while none of the I that that is not filtered (and thus remains in the plasma) is excreted.
Since clearance is defined as the volume of plasma ‘cleared’ of a substance in 1 min, the clearance for I is 125 ml/min. This means that of the 625 ml of plasma that come to the kidney in one minute, 125 ml (the fraction that is filtered) has all of the I removed from it in that minute, the other 500 ml (the fraction that is not filtered) keeps its I as there is no way for the I get into the urine as it is not secreted.
Clinicians and medical doctors will measure the clearance of inulin to determine whether the kidneys of their patients are filtering properly.
Drawbacks inulin method: (3)
o Prolonged infusion
o Repeated plasma samples
o Difficult routine clinical use
The Creatine Method
what do we test clinically?
how is this measured? over how long is it measured?
is the filtration equal to urine excretion? what 2 values will cancel out?
- Clinically use creatinine for GFR measurement
- Blood samples are collected for measurement of plasma creatinine concentration and the patient is provided with an appropriate container and preservative and instructed to collect all urine excreted over the next 24 hours. The urine volume and creatinine concentration is measured and the clearance is calculated.
- It is NOT reabsorbed but a small amount is secreted so really the amount excreted slightly exceeds the amount filtered, but because there’s usually slight error in estimation of plasma [creatinine] these 2 errors cancel each other out and creatinine clearance provides a reasonable estimate of GFR.
The Creatine Method
advantages and disadvantages
5 adv
1 disadv
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
Trimethoprim
what does it do? and what may it cause?
particularly in which patients?
(antibiotic) competitively inhibits renal tubular creatinine secretion and may cause an artificial increase in serum creatinine, particularly in patients with a pre-existing renal insufficiency
Creatine in the body
where is most of creatinine found? why must Cr be taken up from the blood? how?
how is the daily demand for Cr met? (2)
how is muscular cr converted and what rate?
The most part (up to 94%) of Cr is found in muscular tissues. Because muscle has virtually no Cr-synthesising capacity, Cr has to be taken up from the blood against a large concentration gradient by a saturable, Na+- and Cl−-dependent Cr transporter that spans the plasma membrane.
The daily demand for Cr is met either by intestinal absorption of dietary Cr or by de novo Cr biosynthesis. The muscular Cr and PCr are non-enzymatically converted at an almost steady rate (∼2% of total Cr per day) to creatinine (Crn), which diffuses out of the cells and is excreted by the kidneys into the urine.
Creatine supplements - what do they do
3 ways it improves muscle performance?
Even though Cr supplementation is commonly regarded as safe, no proper clinical study has been conducted yet to evaluate the compound’s safety profile in humans. Cr supplementation may improve muscle performance in three different ways:
- By increasing the muscle stores of PCr which is the most important energy source for immediate regeneration of ATP in the first few seconds of intense exercise
- By accelerating PCr resynthesises during recovery periods
- Depressing the degradation of adenine nucleotides and possibly also the accumulation of lactate during exercise.
