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RENAL CLEARANCE. Renal Clearance. Definition: Is the volume of plasma completely cleared of a substance by the kidneys per unit time . The higher the renal clearance, the more plasma that is cleared of the substance. Unit: ml/min. Nephron Excretion & Clearance. Inulin
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Renal Clearance Definition: Is the volume of plasma completely cleared of a substance by the kidneys per unit time. The higher the renal clearance, the more plasma that is cleared of the substance. Unit: ml/min
Nephron Excretion & Clearance Inulin A plant product that is filtered but not reabsorbed or secreted Used to determine clearance rate and therefore nephron function
NephronExcretion & Clearance The relationship between clearance and excretion using a few examples
Equation for renal clearance Cx = Ux x V Px Wherex = substance Cx = clearance of substance Ux = urine concentration of substance Px = plasma concentration of substance V = urine flow rate (ml/min) Amount of substance excreted = (filtered – reabsorbed + secreted) Ux V = GFR x Px ± Tx
Comparison of clearance of a substance with clearance of inulin 1) = inulin clearance; only filtered not reabsorbed or secreted 2) < inulin clearance; reabsorbed by nephron tubules 3) > inulin clearance; secreted by nephron tubules
Examples: clearance of known substances Glucose (0) Urea (40 ml/min) Inulin (125 ml/min) PAH(585 ml/min) 100 200 300 400 500 600 Clearance (ml/min)
Application of renal clearance in kidney function • Inulin clearance can be used to estimate GFR (by calculation) • PAH clearance can be used to estimate renal plasma flow • Measurement of filtration fraction = GFR / RPF • Measurement of creatinine clearance
Inulin clearance If a substance is freely filtered and not reabsorbed or secreted rate of excretion in urine is equal to rate of substance filtered by kidney. Thus, GFR x PS = US x V GFR = Us x V = Cs Ps GFR therefore, can be calculated as follows: Inulin, a polysaccharide molecule with MW of 5200, fits these criteria.
INULIN CLEARANCE GFR = Cin = 125ml/min CREATININE CLEARANCE Ccr = Ucr x V Pcr Where Ccr = creatinine clearance Ucr = urine concentration of creatinine Pcr = plasma concentration of creatinine V = urine flow rate (ml/min)
Creatinine clearance overestimate GFR by 10-20% due to creatinine secretion in very small amounts. Blood urea and creatinine will not be raised above normal range until 60% of total kidney function is lost. Hence, the more accurate GFR or creatinine clearance is measured whenever renal disease is suspected or careful dosing of nephrotic drug is required.
Plasma creatinine: (Normal plasma creatinine in daults = 0.6 – 1.2 mg/dl) 16 12 8 4 0 Index of GFR Plasma creatinine (mg/dl) 0 45 90 135 180 Glomerular filtration rate (L/day)
Relationship between serum creatinine and renal function Plasma creatinine (mg/dL) 2.3 4.5 6.8 9.0 11.3 13.6 120 100 80 60 40 20 Normal Reduced reserve GFR (mL/min) Renal impairment End-stage renal disease 200 400 600 800 1000 1200 Plasma creatinine (µmol/L)
Para-aminohippuric acid (PAH) clearance If a substance is completely cleared from plasma clearance rate is equal to total renal plasma flow amount delivered to kidneys is equal to amount excreted. Thus, RPF = UPAH x V = CPAH PPAH
Renal Blood Flow • Resting condition (adult) receive • 1.2 L/min (25% of CO) • Measurement of RBF • Electromagnetic flow meters • Fick’s principle
Fick Principle • Amount taken up by an organ (kidney) per unit of time divided by the arterio-venous difference of the substance = plasma flow • RPF = amount of substance excreted divided by the renal arterio-venous difference. RPF = UPAH x V RAPAH – RVPAH RVPAH = 0, RPF is described as effective renal plasma flow (ERPF).
Effective RPF (ERPF) Effective RPF = UPAH V PPAH Where: Effective RPF = effective renal plasma flow (ml/min) UPAH = urine concentration of PAH (mg/ml) V = urine flow rate (ml/min) PPAH = plasma concentration of PAH (mg/ml) CPAH = clearance of PAH (ml/min)
Effective RPF = UPAH x V PPAH = 14 mg/ml x 0.9 ml/min 0.02 mg/ml = 630 ml/min Actual RPF = ERPF Extraction ratio = 630 / 0.9 = 700 ml/min The clearance of PAHA reflect only RPF to portions of the kidney that deal with urine formation, and thus underestimate actual RPF by about 10%. The renal extraction ratio of PAH = 0.92
Measuring renal blood flow (RBF) RBF is calculated from RPF and the hematocrit (PCV). Formula is as follows: RBF = RPF RBF = 700 1 – Hct 0.55 = 1273 ml/min Hematocrit (PCV) = 0.45 Where: RBF = renal blood flow (ml/min) RPF = renal plasma flow (ml/min) PCV = hematocrit
Glomerular capillary Substance X Substance Y Substance Z Bowman’s space Urine Urine Urine Renal handling of hypothetical substance X, Y, Z. X, filtered & secreted not reabsorbed Y, filtered, fraction reabsorbed Z, filtered, completely reabsorbed