Renal Blood Flow GFR. Glomerulus Fluid Flow and Forces. Renal Blood Flow (cont d)

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1 GFR Glomerular filtration rate: about 120 ml /minute (180 L a day) Decreases with age (about 10 ml/min for each decade over 40) GFR = Sum of the filtration of two million glomeruli Each glomerulus probably filters about 20 nl/min (ie total GFR divided by number of nephrons) Renal Blood Flow Blood flow to kidney about 1,100 ml/min (plasma 600ml/min) 20% of resting cardiac output is directed to the kidneys If GFR is 120ml/min and plasma flow is 600ml/min then 20% of every mm of plasma passing the glomeruli is diverted into the tubular system as filtrate Ratio of GFR to renal plasma flow is 0.2 and is called the filtration fraction Blood out Renal Blood Flow (cont d) Blood flow to kidneys is kept constant as it is not dependent on metabolic demands Regulation of RBF is designed to sustain high filtration rates not metabolic rates High RBF (low renal vasculature resistance) is due to low resting sympathetic nervous tone and high production of the vasodilator nitric oxide To venous system In pregnancy RBF and GFR are increased (30% - 50%). Due to elevated cardiac output and to enhanced renal nitric oxide production Glomerulus Fluid Flow and Forces Glomerulus capillary hydrostatic pressure is higher than pressure in other capillaries because of the presence of the efferent arteriole which exerts a post-capillary resistance Blood out To venous system

2 Regulation of GFR Changes in GFR can occur from Structural changes Changes in filtration pressure Structural changes Renal hypertrophy causes an increase in GFR When one kidney is removed, either due to disease or to donate, the other kidney undergoes a growth of both blood vessels and tubules (hypertrophy), ie nephrons grow Hypertrophy is usually complete in 4 weeks, and the GFR has returned to normal ie the remaining kidney has doubled its GFR without increasing the number of nephrons. Changes in afferent arteriole resistance is the most common physiological regulator of GFR Increase in afferent resistance (ie vasoconstriction) decreases GFR Less Less Filtrate Changes in afferent arteriole resistance is the most common physiological regulator of GFR Increase in afferent resistance (ie vasoconstriction) decreases GFR Decrease in afferent resistance (vasodilation) increases GFR

3 More Changes in afferent arteriole resistance is the most common physiological regulator of GFR Increase in afferent resistance (ie vasoconstriction) decreases GFR More Filtrate Decrease in afferent resistance (vasodilation) increases GFR Arteriole tone (ie contraction or dilation) can be due to presence of vasoactive agents, eg angiotensin, nitric oxide; or due to changes in sympathetic tone (epinephrine and norpeinephrine) Changes in efferent arteriole resistance Less blood out Vasoconstriction of the efferent arteriole increases the hydrostatic pressure in the capillaries of the glomerulus as it acts like a dam, and GFR increases More Filtrate Changes in efferent arteriole resistance More blood out Vasoconstriction of the efferent arteriole increases the hydrostatic pressure in the capillaries of the glomerulus as it acts like a dam, and GFR increases Less Filtrate Dilation of the efferent arteriole decreases glomerular capillary hydrostatic pressure, therefore GFR decreases

4 Renal obstructions Blood out These tend to decrease GFR, as a blockage in a renal tubule exerts a pressure back on the glomerulus that reduces filtration Obstruction can be due to cell necrosis, or lower urinary tract blockage e.g. kidney stone, which blocks urine flow Less Filtrate To venous system Autoregulation of GFR Afferent arteriole resistance when altered changes GFR. However, usually the changes in resistance are a compensation so that GFR remains constant Arterial Pressure Decreases in arterial pressure causes less blood flow to the renal artery, but GFR remains constant as the afferent arteriole compensates by vasodilating (resistance decreases) keeping blood flow to the gomerulus constant A change in arterial pressure is the most common perturbation associated with autoregulation of GFR Arterial Pressure Decreases in arterial pressure causes less blood flow to the renal artery, but GFR remains constant as the afferent arteriole compensates by vasodilating (resistance decreases) keeping blood flow to the gomerulus constant Conversely, if arterial pressure increases, the afferent arteriole constricts (resistance increases) so that the increase in arterial pressure is not transmitted to the glomerulus and GFR remains constant Range of autoregulation is an arterial pressure of between mm Hg

5 Mechanisms of Alterations in Afferent Arteriole Resistance Myogenic : smooth muscle changes in the arteriole, smooth muscle will contract when wall tension increases Tubuloglomerular feedback This is the term for a circuit designed to keep NaCl concentrations at the macula densa, and therefore, concentrations of Na that enter the collecting duct, constant. Tubuloglomerular feedback : signal comes from the renal tubule (nephron) Conservation of sodium by the different segments of the nephron Proximal tubule 67% 16,800 meq/day MACULA DENSA Distal tubule 5% 1260 meq/day Tubuloglomerular feedback This is the term for a circuit designed to keep NaCl concentrations at the macula densa, and therefore, concentrations of Na that enter the collecting duct, constant. Thick ascending limb 25% 6300 meq/day Collecting duct 3% 750 meq/day NaCl concentration at the macula densa can control the tone of the afferent arteriole, and therefore controls GFR. Tubuloglomerular feedback (cont d) Increased NaCl concentration at the macula densa causes afferent arteriole to constrict, which leads to less pressure for filtration, so GFR decreases This decline in GFR now limits how much Na reaches the macula densa, and how much is delivered to the distal nephron (equilibrium is maintained) Conservation of sodium by the different segments of the nephron Proximal tubule 67% 16,800 meq/day Thick ascending limb 25% 6300 meq/day MACULA DENSA Distal tubule 5% 1260 meq/day Collecting duct 3% 750 meq/day

6 Tubuloglomerular feedback (cont d) Increased NaCl concentration at the macula densa causes afferent arteriole to constrict, which leads to less pressure for filtration, so GFR decreases This decline in GFR now limits how much Na reaches the macula densa, and how much is delivered to the distal nephron (equilibrium is maintained) Decreased NaCl concentration at the macula densa causes afferent arteriole to relax (vasodilate) so more blood enters as less resistance, so pressure for filtration increases, and GFR increases Clinical Considerations Autoregulation response serves to protect the glomerulus from elevated blood pressure (arterial pressure) Constant high blood pressure is associated with the development of pathology in the glomerular structure and function, and autoregulation is lost Hypertension (sustained high blood pressure) has to caused by a defect in renal function (loss of autoregulation) and not due to changes in vasculature (eg cardiac output, peripheral resistance etc) Diabetes Diabetes in its early stage causes dilation of afferent arteriole (glucose is high in plasma) and results in an increase in the glomerular capillary pressure, which contributes to the glomerular damage in these patients