What should be mentioned?
Clearance = volume (of plasma) from which all test substances are removed/min (cleared) (ml/min).
It is a measure of the ability of the kidney to remove a substance from the blood plasma and to forward it to the urine (to put it in another way: clearance is the efficiency with which the plasma is cleared of a given substance).
Importance of application of clearance method:
-independent of the actual plasma concentration
-excretion of any substances can be expressed in same unit(ml/min)
- functional standards of the kidney can be determined by the clearance of certain substances:
• Inulin = GFR
• PAH = RPF
-Certain functional disorderes can be quantitatively characterised by clearance.
GFR - RPF
-All filtered substances have a clearance value. Certain selected substances are exclusively filtered (they are neither rebsorbed, nor secreted - e.g. inulin), their clearance is equal to the rate of glomerular filtration rate (GFR).
-Some other substances are entirely secreted (like para-amino-hyppuric acid), the clearance of these gives the renal plasma flow (RPF)
-When comparing the clearance of a substance with the inulin clearance one can tell the way at which the substance is excreted. If its clearance is higher than that of the inulin, then it is secreted, if smaller, then it is reabsorbed. The clearance of glucose is 0, because it is totally reabsorbed. The clearance of urea is smaller than that of inulin: since it is partly reabsorbed but excreted as well.
Clearance of para-amino-hippuricacid
The clearance of para-amino-hippuricacid, PAH is constant at low plasma concentrations.
At higher concentrations, however, the secretory capacity of the tubules decreases, some tubular become unable to secrete more PAH (active transport!): so its clearance decreases.
At a certain plasma concentration all the tubular cells reach the maximum of their transport capacity (maximum PAH secretion - transport maximum, Tm): from this point on the excretion does not grow with secretion, and the clearance becomes constant at a low value.
Clearance of inulin
The inulin is typically such a substance that is only filtered: it is neither reabsorbed nor secreted. According to this its concentration in the plasma does not influence its clearance even under extremely high values.
Urea is freely filtered, and then passively moves among those parts of each tubule sections, which are permeable for urea. A portion of the filtered amount of this substance always remains in the interstitium, but the capacity of filtration is unlimited for this substance as well: therefore the clearance is obligatorily smaller than that of inulin, but does not depend on plasma concentration. In case of tubular cell diseases the urea recirculation gets damaged: the urea content of the blood then increases, uraemia forms.
Glucose is filtered freely, but under normal proximal tubular activity glucose does not get into the descendent limb of the Henle-loop: it is entirely reabsorbed in the proximal tubule. Therefore under normal glucose plasma concentrations the clearance of glucose = 0. In diabetes the glucose level of the plasma increases so much, that the tubular cells become unable to reabsorb it (active transport!), so the transfer maximum or reabsorption maximum (TmGlucose) is reached: therefore, glucose appears in the urine.
The extraction characterizes the ability of the kidney to eliminate a subtance from the organism.
In the renal artery a certain amount of substance in a certain concentration arrives at the kidney, and the same or reduced amount leaves through the vein.
The extraction can refer to the whole kidney or to one glomerulus.
In the case of one given substance the measured extraction can be maximal at the glomerular level, however some nephrons in the kidney are not functioning. Therefore the extraction of the given substance at the level of the whole kidney will be less.
3. Renal plasma flow
According to Flick-principle: the amount of substance entering the kidney on the arterial side per unit time (mg/min), must be equal to the sum of the amounts of the substance leaving the kidney with the renal vein and with the urine.
4. Renal blood flow (RBF)
RBF = RPF/ 1 – Htc
Distribution of blood flow in tissue layers of kidney
90 % cortical
8 -9 % outer medullary
1 -2 % inner medullary zone (exclusively v. recta!)
5. Glomerular filtration rate (GFR)
-GFR, the glomerular filtration rate is the amount of filtrate produced per unit time by all of the nephrones of the two kidneys.
It is one of the most important parameters of renal function.
-The GFR can be measured by inulin and creatinine. The creatinine is the physiological muscle metabolit.
-Filtered load (FL, mg/min) of a given substance is the amount of it that is ultrafiltered per unit time [mg substance/min] (its other name is: filtration capacity).
Factors in association with GFR
Substantial changes of RBF do not substantially influence GFR (autoregulation).
Changes of glomerular pressure results in similar changes of GFR (however
autoreg. reduces that change).
Extreme increase in capsular pressure reduces the GFR (i.e. ureter obstruction).
Increase of GCP (Glom.Colloid Osmotic Press.) decreases GFR (1 Hgmm increase = 5 – 10% GFR decrease).
Glomerular membrane permeability (pathogenic) decreases GFR.
Reduced total filtration surface (nephrectomy): decreases GFR.