The Renal System

Objectives To define clearance To describe how to measure GFR using the clearance of Inulin and Creatinine To describe how to measure renal blood flow using the clearance of Para-aminohippurate

Measurement of Glomerular Filtration Rate (GFR)

Clearance Cx = Ux X Vml/min px Cx = clearance of substance x Clearance is the volume of plasma from which a substance is completely cleared to be excreted in urine per unit time. Clearance of substance x is calculated as follows: Cx = Ux X Vml/min px Cx = clearance of substance x Ux = concentration of substance x in urine V = urine volume per unit time (urine flow rate) Px = concentration of substance x in plasma

Clearance Clearance is used to: Measure glomerular filtration rate (GFR) Measure Renal Plasma Flow (RPF) Assess tubular transport mechanism Assess GFR & RPF in patients

Characteristics of a substance suitable for measuring the GFR by determining its clearance: Freely filtered (i.e. not bound to protein in plasma). Not reabsorbed by tubules Not secreted by tubules Not metabolised Not stored Not toxic Has no effect on filtration rate Preferably easy to measure in plasma and urine

Inulin Clearance Amount filtered cortex medulla Inulin Clearance Amount filtered Amount filtered = GFR x Plasma concentration Amount filtered = GFR x Px Amount excreted = Urinary concentration x Urine volume Amount excreted Amount excreted = Ux x V

Measurement of GFR GFR x Pc = Uc x Vml/min GFR = Uc x V Pc amount filtered = amount excreted GFR x Pc = Uc x Vml/min GFR = Uc x V ml/ min Pc

Fructose polymer, molecular weight 5200. Measurement of GFR Substances used to measure GFR: Inulin: Fructose polymer, molecular weight 5200. Procedure: an intravenous load of inulin is administered followed by sustained infusion of inulin until plasma level is constant. urine is collected for a timed period to get urine flow rate and urinary concentration of inulin.

Measurement of GFR Creatinine product of metabolism of creatine phosphate in muscles. plasma concentration =< 1 mg/dL. Procedure: urine is collected for 24 hours. a sample of plasma to measure creatinine is obtained at mid-time collection of urine.

Renal Blood Flow Measurement (RBF) The substance used is Para amino hippurate (PAH). Characteristics: easily filtered not reabsorbed highly secreted not metabolized not synthesised not stored

Renal Blood Flow Measurement RBF Fick’s equation: RBF = Qx RAx-RVx Qx = rate at which substance x consumed RAx concentration of x in renal artery RVx = concentration of x in renal vein If we apply this equation to plasma then RPF = Qx PRAX -PRVX

Renal Blood Flow Measurement RBF If substance x is not metabolised or synthesised or stored, then rate of consumption by the kidney can be equated to the rate of its excretion. (Ux X V) If substance x is not metabolized by other tissues, then PRAx=Px If substance x is highly secreted, then PRVx =0

Renal Blood Flow Measurement RBF Then RPF = Ux X V Px Renal vein plasma concentration of PAH is not zero as 10-15% is not cleared PAH clearance=effective renal plasma flow ( ERPF) RPF = ERPF X 100 90 RBF = RPF X 100 (100-Hct) Hct = heamatocrit RPF = 625 ml/min

Objectives To describe the factors that modify GFR

Factors Affecting GFR 1. changes in renal blood flow

Factors Affecting GFR changes in systemic blood pressure 2. changes in glomerular capillary hydrostatic pressure changes in systemic blood pressure afferent or efferent arteriolar constriction

Factors Affecting GFR a. ureteric obstruction 3. changes in hydrostatic pressure in Bowman’s capsule a. ureteric obstruction b. Edema of kidney inside tight renal capsule

Factors Affecting GFR 4. Changes in capillaries oncotic pressure.

Factors Affecting GFR 5. increased permeability of glomerular filtration membrane: Various diseases

Factors Affecting GFR 6. decrease in total area of glomerular capillary bed a. Diseases that destroy glomeruli with or without destruction of tubules b. Partial nephrectomy.

Factors Affecting GFR Summary 1. changes in renal blood flow 2. changes in glomerular capillary hydrostatic pressure a. changes in systemic blood pressure b. afferent or efferent arteriolar constriction 3. changes in hydrostatic pressure in Bowman’s capsule ureteral obstruction Edema of kidney inside tight renal capsule

Factors Affecting GFR Summary 4. Changes In capillaries Oncotic pressure. 5. increased permeability of Glomerular. filtration membrane: various diseases. 6. decrease in total area of Glomerular capillary bed. a. Diseases that destroy Glomeruli with or without destruction of tubules b. Partial nephrectomy.