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RENAL CLEARANCE

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

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  1. RENAL CLEARANCE

  2. 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

  3. Nephron Excretion & Clearance Inulin A plant product that is filtered but not reabsorbed or secreted Used to determine clearance rate and therefore nephron function

  4. NephronExcretion & Clearance The relationship between clearance and excretion using a few examples

  5. NephronExcretion & Clearance

  6. 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

  7. 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

  8. 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)

  9. 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

  10. 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.

  11. 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)

  12. 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.

  13. 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)

  14. 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)

  15. 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

  16. Renal Blood Flow • Resting condition (adult) receive • 1.2 L/min (25% of CO) • Measurement of RBF • Electromagnetic flow meters • Fick’s principle

  17. 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).

  18. 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)

  19. 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

  20. 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

  21. 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

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