Clearance: FeNa Flashcards
Equation to calculate renal elimination
Renal elimination = Filtered Load - Reabsorbed Load + Secreted Load
What is renal clearance?
The volume of plasma from which a specific compound is completely eliminated (cleared) per unit time
Thus, clearance is a flow rate
Input occurs via the renal artery. How is input calculated?
Input = (Pax) x (RPFa)
Where:
Pax = arterial concentration of X (mg/ml)
RPFa = renal arterial plasma flow (ml/min) aka rate of entry into kidney
Output occurs via the renal vein. How is the venous effluent calculated?
Venous effluent = (Pvx) x (RPFv)
Where:
Pvx = renal v. plasma concentration of x (mg/min)
RPFv = renal plasma flow
Output is via urine; how is urinary excretion rate calculated?
Urinary excretion rate = (Ux) x (V)
Where:
Ux = urine concentration of x (mg/ml)
V = urine flow rate (ml/min)
A clearance calculation provides the answer to, “From how many mLs of plasma entering the kidney per min was substance X removed?”. How is clearance calculated?
Cx = [(Ux) x (V)]/Px
Or:
Cx = (urinary excretion rate)/Px
When does the renal elimination rate (i.e., clearance) equal the GFR?
When a substance is freely filtered but neither reabsorbed nor secreted
Explicit requirements of a substance suitable for measurement of GFR
Freely filtered across glomerulus (i.e., not bound to plasma proteins)
Undergoes no tubular reabsorption or secretion
Is neither metabolized nor synthesized in the kidney
Does not alter GFR
What water-soluble substance is freely filtered but neither reabsorbed nor secreted, and thus its clearance can be used to measure GFR?
Inulin
What endogenous water-soluble substance is freely filtered but neither reabsorbed nor secreted and can be used to approximate the GFR based on its clearance?
Creatinine
What substance is completely eliminated (i.e., filtered and secreted but not reabsorbed) from the plasma during passage through the kidney, and what can it be used to measure?
Para-amino hippurate (PAH)
Its clearance = effective RPF (because ~10% of RPF does not enter peritubular capillaries), note that it works for low plasma concentrations only
How is RBF calculated?
RBF = RPF/(1-Hct)
Equation for filtered load
FL = GFR x Px
What is the meaning of a filtered load > excreted load and vice versa?
FL > EL means there is net reabsorption of the filtered solute
EL > FL means there is net secretion of the filtered solute
What is the range of values for clearance?
0-RPF
[you get 0 if substance is filtered but completely reabsorbed, like glucose, amino acids, often HCO3, etc]
______ is widely available since it is used in radiological procedures; it is also the current default means of measuring GFR in pts since it is freely filtered and not reabsorbed. There is error in this method because, unlike inulin, it undergoes some tubular secretion, but this can be blocked if desired with ______
125-I-iothalamate (GloFil); probenecid
___ is a 120 aa peptide that is freely filtered, then digested/reabsorbed by proximal tubules. With constant rate of synthesis, the plasma concentration should be a reflection of the GFR
Cystatin C
With normal sodium intake, what is considered a normal fractional excretion of sodium (FeNa)?
Typically near 1%
If GFR is low (i.e., serum creatinine is high), and FeNa is very low (e.g., 0.1%), what does that mean for the pts renal function?
Tubules are alive with massive reabsorption of a small amount of tubular fluid (acute kidney injury due to pre-renal ischemia, kidney can recover relatively quickly)
If GFR is low (i.e., serum creatinine is high), and FeNa high, what does that mean for the pts renal function?
Significant nephron death is occurring, causing disrupted reabsorption of filtrate (acute kidney injury due to acute tubular necrosis, slow to recover)
Equation used to calculate fractional excretion of sodium
FeNa = Na excreted/Na filtered = [U(Na) x V] / [P(Na) x GFR]
Note GFR = [U(Cr) x V]/P(Cr), so can be simplified to FeNa = C(Na)/C(Cr)
Spot urine protein allows a rough assessment of daily protein loss when there is protein in the urine. What does it mean if > 3-3.5 g is lost per day?
It is being lost faster than the liver can replace it
Spot urine protein equation
Protein excreted (g/day) = U(pro)/U(Cr)
Only a fraction of the plasma that enters the glomerulus is filtered. What must happen for the clearance of a solute to exceed the GFR?
Tubular secretion
Clearance of PAH is considered a measurement of effective Renal Plasma Flow (or eRPF), what is meant by “effective”?
Blood perfusing the renal pelvis and some juxtamedullary nephrons bypasses the proximal tubule basolateral membrane (roughly ~10% is not included in calculation)
PCr will increase until UCrV equals ____
mg creatinine produced per minute
As GFR falls, the fraction of the total mass of creatinine ending up in the urine that was contributed by the proximal tubule ______, also helped in part by the ______ PCr
[increase/decrease?]
Increases; increased
Cockcroft-Gault GFR calculation
[(140-age) x kg] / [ serum creatinine x 72]
Multiply by 0.85 for females
Assume that a pt was supposed to have a timed collection of urine and plasma to assess renal function. An IV infusion was set up for 0.5 ml/min infusion of normal saline containing inulin and PAH. The anticipated steady-state plasma levels for inulin and PAH were 1 mg/ml and 0.1 mg/ml, respectively. However, due to a math error during infusion solution preparation, the inulin concentration in the infusion solution was doubled.
As a result of this error, what changes take place in C(inulin), C(PAH), U(In)V, FE(inulin)
C(inulin) = unchanged
C(PAH) = unchanged
U(In)V = doubled
FE(inulin) = unchanged
Assume that a pt was supposed to have a timed collection of urine and plasma to assess renal function. An IV infusion was set up for 0.5 ml/min infusion of normal saline containing inulin and PAH. The anticipated steady-state plasma levels for inulin and PAH were 1 mg/ml and 0.1 mg/ml, respectively. However, due to a math error during infusion solution preparation, the inulin concentration in the infusion solution was doubled.
Had there not been this math error, but the steady-state plasma level for inulin for this pt was nevertheless 2 mg/ml, what change would you expect in the C(inulin)?
C(inulin) was halved
Assume a pt was supposed to have a timed collection of urine and plasma to assess renal function using a 0.5 ml/min infusion of inulin and PAH intended to generate plasma concentrations of 1 mg/ml and 0.1 mg/ml, respectively. The nurse accidentally dilutes the solutes to twice their intended volume of normal saline (i.e., concentrations are halved). In an attempt to hide this error, the nurse doubles the infusion rate to 1.0 ml/min.
What changes would you expect in C(inulin), C(PAH), U(In)V, and FE(inulin)?
All unchanged
Creatine phosphate serves as the storage form for ATP in muscle to be used during contraction. Without this ATP storage, muscles would consume all their ATP in a few seconds. In an attempt to increase the size of this rapidly-available energy resource, athletes began taking creatine as a nutritional supplement. This caused considerable alarm/confusion amongst healthcare providers because blood tests of the young athletes showed serum creatinine values indicative of severe renal failure.
If a 24 hr urine collection was examined, what changes would be expected in the C(Cr) and U(Cr)V?
C(Cr) would likely be unchanged because the U(Cr)V was increased
What must happen to obtain a value other than 0 for renal glucose clearance? what are the consequences of this?
Glucose transporters must be saturated
Consequences include osmotic retention of tubular fluid manifesting as polyuria offset by polydipsia
Why is the microalbuminuria test used in diabetic patients?
Provides a sensitive test for kidney damage; measures trace amounts of albumin below the detection limit of urine dipstick
