Dr. Rida Shabbir DPT IPMR KMU 1

Objectives Describe the concept of renal plasma clearance Use the formula for measuring renal clearance Use clearance principles for inulin, creatinine etc. for determination of GFR Use PAH clearance for measuring renal plasma flow Calculate Renal Blood Flow 2

RENAL PLASMA CLEARANCE It is the volume of plasma cleared of a substance per unit time Useful way of quantifying the excretory function of the kidneys the rate at which blood flows through the kidneys the basic functions of the kidneys: glomerular filtration, tubular reabsorption, and tubular secretion. Plasma clearance is calculated by the formula: C s = Us x V Ps C s = clearance of a substance U s = urine concentration of a substance V = volume of urine ml/min P s = plasma concentration of a substance 3

CLEARANCE Inulin clearance is used to measure GFR {Glomerular Filtration Rate}  WHY ? Because Inulin is filtered but not reabsorbed or secreted If a substance X [Inulin] is filtered from 125ml/min, then it is excreted but not reabsorbed, not secreted, therefore, 125ml of filtrate is cleared of substance X. 4

CLEARANCE Inulin is used to measure GFR Inulin is a carbohydrate, polysaccharide, not produced in the body but found in certain plants Inulin is infused I/V continuously to maintain a constant plasma level 5

CLEARANCE If U in = 30mg/ml of urine, V = 1.25ml/min, P in = 0.3mg/ml in plasma then C Inulin = (30 × 1.25)/ 0.3 GFR = 125ml/min 6 C inulin = P in U in x V GFR =

CREATININE CLEARANCE In clinical practice endogenous substance Creatinine is often used to find GFR Creatinine is end product of muscle metabolism Creatinine is filtered, not reabsorbed,but slightly secreted, therefore, creatinine clearance is not so accurate for measurement of GFR as Inulin But creatinine clearance provides close approximate value and easy to use as it does not require I/V injection 7

8 Steady-state relationship between GFR and serum creatinine concentration

PARA AMINO HIPPURIC ACID (PAH) PAH clearance is used to measure renal plasma flow WHY ? Because PAH is filtered, not reabsorbed but secreted from all the plasma that flows through the kidneys Renal plasma flow is 650ml/min 9

Theoretically, if a substance is completely cleared from the plasma, its clearance rate would equal renal plasma flow. Use of Clearance to Estimate Renal Plasma Flow Cx = renal plasma flow 10

PAH clearance example

PAH CLEARANCE PAH is 90% cleared from the plasma called extraction ratio Renal plasma flow (RPF) can be calculated by PAH CLEARNCE U = 5.85mg/ml V = 1 ml/min P = 0.01mg/ml Therefore, C = (5.85 × 1)/0.01 RPF = 585 ml/min 12 CPAH = U PAH x V P PAH

PAH CLEARANCE Actual Renal Plasma Flow can be calculated by dividing 585/0.9 = 650ml/min We are dividing by 0.9 because PAH removed from the plasma i.e extraction ratio is about 90% in normal kidneys 13

BLOOD FLOW THROUGH THE KIDNEYS We apply formula If renal plasma flow = 650ml/min HCT = 0.45 Therefore, 14 RBF = RPF 1 - Hct RBF = RBF = = 1182ml/min

REABSORBTION AND SECRETION OF SUBSTANCES If a substance has clearance rate equal to Inulin then substance is only filtered but not reabsorbed, not secreted If a substance clearance rate is less than Inulin clearance, then substance has been reabsorbed by nephron tubule E.g. Urea If clearance rate of a substance is greater than that of Inulin then substance must be secreted by nephron tubule e.g. creatinine 15

16 Plasma Clearance For substances handled in different ways by the kidney Inulin Urea Glucose PAH

CLEARANCE RATE Substance Glucose Na + K + Inulin Creatinine Urea PAH Clearance Rate (ml/min)

Clearance Discussion 18

Q1. What is Plasma Clearance? 19

Q2. Which substance is used to measure i) GFR ii). Renal Plasma Flow 20

Q3. What is the formula for the clearance? 21

Q4. If a substance is filtered, then some of it is reabsorbed, its clearance will be less or more than Inulin clearance? 22

Q5. If a substance is filtered, then secreted, its clearance will be less or more than Inulin clearance? 23

Q6. What is the plasma clearance of i). Glucose ii). Inulin iii). Creatinine iv). Urea v). PAH 24

Thank you 25