Renal Blood Flow & Renal Plasma Flow Lecture 2024 PDF

1502 Renal Blood Flow & Renal Plasma Flow Fall 2024 Lecture 24 Wednesday, Oct 16: 9am...

1502 Renal Blood Flow & Renal Plasma Flow Fall 2024 Lecture 24 Wednesday, Oct 16: 9am Dr. Layla Al-Nakkash [email protected] 1 © L. Al-Nakkash 2020  Learning Objectives 1. Identify the route of blood flow in the kidney. 2. Describe how renal blood flow (RBF) is regulated. 3. Describe the autoregulation of RBF. 4. Describe how PAH is used to estimate renal plasma flow (RPF). 5. Describe how the hematocrit and RPF is used to calculate RBF. © L. Al-Nakkash 2024 2  Renal Vasculature Blood enters the kidneys via the renal artery. The renal artery branches and the smallest arteries subdivide into the first set of arterioles (the afferent arterioles). These deliver blood to the first capillary network, the glomerular capillaries (where ultrafiltration occurs). Blood leaves the glomerulus via a second set of arterioles (the efferent arterioles). These deliver blood to the second capillary network, the peritubular capillaries (surrounding the nephrons, where solutes and water are reabsorbed). Blood from the peritubular capillaries flows into the small veins, then renal vein. 3 © L. Al-Nakkash 2024 1. Identify the route of blood flow in the kidney.  Renal Vasculature In the superficial cortical nephrons: peritubular capillaries branch off the efferent arterioles and deliver nutrients to the epithelial cells. – These serve as the blood supply for reabsorption and secretion. In the juxtamedullary nephrons: peritubular capillaries have a specialization – the vasa recta. – These are long hairpin shaped blood vessels that follow the loop of Henle. – These serve as osmotic exchangers for the production of concentrated urine. 4 © L. Al-Nakkash 2024 1. Identify the route of blood flow in the kidney.  Renal Blood Flow – The kidneys receive 25% of the cardiac output. Pretty high – If a person has a cardiac output of 5 L/min, what would the renal blood flow (RBF) be? 5L x 0.25 = 1.25 L/min 1.25 L/min x 60 min x 24 hr = 1800 L/day – This high RBF is important given the role the kidneys play in maintaining volume and composition of body fluids. It supports the filtration role 5 © L. Al-Nakkash 2024 2. Describe how renal blood flow (RBF) is regulated..  Regulation of Renal Blood Flow What is renal blood flow related to? Pressure gradient & Resistance Directly proportional to the pressure gradient across the renal artery and renal vein. Note: the kidney has 2 sets of arterioles: afferent and efferent Inversely proportional to the resistance of the renal vasculature. This is the major mechanism to change RBF Q=∆P R 6 © L. Al-Nakkash 2024 2. Describe how renal blood flow (RBF) is regulated..  Regulation of Renal Blood Flow 7 © L. Al-Nakkash 2024 2. Describe how renal blood flow (RBF) is regulated..  Regulation of Renal Blood Flow Sympathetic nervous system – Renal afferent and efferent arterioles have SNS innervation. – vasoconstriction When stimulated this produces ________________. – By activation of ɑ1 receptors. – There are a lot of these ɑ1 receptors on the afferent arteriole, thus, SNS activation results in vasoconstriction and decreased RBF (and ↓ GFR). Clinical example when this occurs: Hemorrhage Blood loss ↓ mean arterial pressure (↓ blood pressure) ↓ baroreceptor firing ↑ SNS activity ↑ SNS activity to the kidney to → 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑜𝑜𝑜𝑜 𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 Heart and blood vessels →↓ RBF and ↓ GFR To ↑ HR & contractility, constrict veins to ↑ VR To try and ↑ BP back to normal 8 © L. Al-Nakkash 2024 2. Describe how renal blood flow (RBF) is regulated..  Regulation of Renal Blood Flow Angiotensin II – Acts on renal afferent and efferent arterioles. Results in potent vasoconstriction ↓ – ________________. – Constriction of both sets of arterioles results in increased resistance and ____ RBF. – Efferent arterioles are MORE sensitive to angiotensin II than afferent arterioles. ↓ levels of angiotensin II ↑GFR By preferentially constricting efferent arterioles ↑ levels of angiotensin II ↓GFR By constricting BOTH efferent & afferent arterioles 9 © L. Al-Nakkash 2024 2. Describe how renal blood flow (RBF) is regulated.  Regulation of Renal Blood Flow Angiotensin II – Acts on renal afferent and efferent arterioles. – Results in potent vasoconstriction ________________. – ↓ RBF. Constriction of both sets of arterioles results in increased resistance and ____ – Efferent arterioles are MORE sensitive to angiotensin II than afferent arterioles. In Hemorrhage Blood loss ↓ MAP (blood pressure) Activates RAAS Renin-angiotensin- aldosterone system ↑ levels of angiotensin II Renin converts Angiotensinogen to Angiotensin I, + ↑ SNS activity then ACE converts Ang I to Ang II constriction of efferent & afferent arterioles ↓ RBF & GFR 10 © L. Al-Nakkash 2024 2. Describe how renal blood flow (RBF) is regulated.  Regulation of Renal Blood Flow Atrial Natriuretic Peptide (ANP) – Results in DILATION of renal afferent and constriction of efferent arterioles. – Dilatory effect (on afferents) is GREATER than the constrictor effect (on efferents). – Results in decreased resistance and ____ ↑ RBF. – ↑ GFR. Dilation of afferents and constriction of efferents results in ___ Prostaglandins Pg I2 and E2 – Results in DILATION of renal afferent and efferent arterioles. – In hemorrhage: activation of SNS and increase angiotensin II will also increase renal prostaglandin production. – Prostaglandin production serves to reduce the vasoconstriction induced from SNS and angiotensin II. Helps mitigate renal failure that can result from decreased RBF 11 © L. Al-Nakkash 2024 2. Describe how renal blood flow (RBF) is regulated.  12 © L. Al-Nakkash 2024 2. Describe how renal blood flow (RBF) is regulated.  13 © L. Al-Nakkash 2024 2. Describe how renal blood flow (RBF) is regulated.  Autoregulation of Renal Blood Flow RBF is autoregulated over a wide range of mean arterial pressure (Pa). RBF is constant between 80- RBF is constant 200 mmHg When Pa= 80-200 mmHg When Pa decreases below 80 mmHg then RBF decreases. Rennin-angiotensin- To maintain RBF while arterial aldosterone system pressure changes – we need resistance Q= ∆P/R to vary_________. Autoregulation is controlled at the level of the afferent arterioles. ANS is not involved in autoregulation How do we know this? A transplanted kidney autoregulates 14 © L. Al-Nakkash 2024 3. Describe the autoregulation of renal blood flow (RBF).  Autoregulation of Renal Blood Flow Myogenic hypothesis: ↑ Pa, stretches vessels, reflexly contracting smooth muscle in the walls of the vasculature & resulting in ↑ resistance to blood flow. Stretch-induced contraction – opens stretch-activated Ca2+ channels. i.e., More Ca2+ entering the SMC will create more contraction/tension Afferent arteriolar contraction ➞ ↑ afferent arteriolar resistance. This balances the ↑Pa and RBF stays constant. Tubuloglomerular feedback: When Pa and renal arterial P ↑ ➞ immediate ↑ in both RBF and GFR. ↑ GFR ➞ ↑ delivery of solutes & water to macula densa. – This senses the increased load & secretes adenosine to constrict afferent arterioles ➞ resulting in vasoconstriction of afferent arterioles. What will this do the RBF and GFR? Decrease them back to normal Reminder: The macula densa cells are part of the juxtaglomerular apparatus 15 © L. Al-Nakkash 2024 3. Describe the autoregulation of renal blood flow (RBF).  Autoregulation of Renal Blood Flow Tubuloglomerular feedback: ↑ GFR ➞ ↑ delivery of solutes & water to macula densa. ↑ Na and Cl delivered – Both are transported into the macula densa cells by Na/K/2Cl-co-transporter ↑ IC [Cl ] depolarizes the macula densa basolateral membrane and opens Ca channels ➞ ↑ IC [Ca2+]. ↑ IC [Ca2+] ➞ ↑ adenosine from macula densa cells. Adenosine (acts locally) ➞ vasoconstricts afferent arterioles ➞ ↓ RBF and GFR back to normal 16 © L. Al-Nakkash 2024 3. Describe the autoregulation of renal blood flow (RBF).  17 © L. Al-Nakkash 2024 3. Describe the autoregulation of renal blood flow (RBF).  Measurement of Renal Plasma Flow & Renal Blood Flow Renal plasma flow can be estimated from the clearance of para- aminohippuric acid (PAH) PAH is an organic acid Renal blood flow can be calculated from renal plasma flow and the hematocrit. Infusion with PAH, sample urine, sample blood from renal artery & renal vein. PAH can be used to measure RPF. Amount of PAH Amount of PAH Amount excreted entering the kidney = = leaving the kidney= + in urine [RA]PAH x RPF [RV]PAH x RPF [U]PAH x V 18 © L. Al-Nakkash 2024 4. Describe how PAH is used to estimate renal plasma flow (RPF).  Measurement of Renal Plasma Flow Why use PAH to measure RPF? Neither metabolized nor synthesized by the kidney. PAH does not alter RPF. Essentially all of PAH entering the kidney (via renal artery) is excreted in urine & little leaves via renal vein. Amount of PAH Amount of PAH Amount excreted entering the kidney = = leaving the kidney= + in urine [RA]PAH x RPF [RV]PAH x RPF [U]PAH x V 19 © L. Al-Nakkash 2024 4. Describe how PAH is used to estimate renal plasma flow (RPF).  Measurement of Effective Renal Plasma Flow- clearance of PAH – We assume [RV]PAH = 0 Most of PAH entering kidney via RA is excreted in the urine via filtration & secretion. – We assume [RA]PAH = [PAH] in any peripheral vein Which can readily be sampled Therefore, the equation for RPF is: RPF: Renal plasma flow Effective RPF = _[U]PAH x V_ = CPAH [U]PAH: [PAH] in urine V = Urine flow rate PPAH: [PAH] in plasma [P]PAH CPAH: clearance of PAH Effective RPF = clearance of PAH 20 © L. Al-Nakkash 2024 4. Describe how PAH is used to estimate renal plasma flow (RPF).  Measurement of Renal Blood Flow Renal blood flow is calculated by using renal plasma flow and hematocrit. Hematocrit is the fraction of blood volume that is occupied by red blood cells. Thus, 1-hematocrit is the fraction of blood volume occupied by plasma. RBF = _RPF_ 1-Hct RBF: Renal Blood flow RPF: renal plasma flow Hct: hematocrit 21 © L. Al-Nakkash 2024 5. Describe how the hematocrit and RPF is used to calculate RBF.  Measurement of RBF Sample problem: A patient has a urine flow of 1 ml/min, a plasma [PAH] of 1 mg% and a urine [PAH] of 600 mg%. The patient’s hematocrit is 0.45. What is the patient’s RBF? Effective RPF = _[U]PAH x V_ = CPAH [P]PAH Effective RPF = _600 mg/100ml x 1 ml/min_ = 600 ml/min 1 mg/100ml RBF = _600 ml/min_ = 600 ml/min RBF = _RPF_ 1 - 0.45 = 1091 ml/min 1-Hct 0.55 ANSWER: RBF = 1091 ml/min 22 © L. Al-Nakkash 2024 5. Describe how the hematocrit and RPF is used to calculate RBF.  Blood flow is directly related to the pressure gradient True / False Activation of SNS results in renal vasodilation True / False Angiotensin II is a potent renal vasoconstrictor True / False With  renal Pa there is an  GFR &  delivery of solutes to the macula densa True / False RBF is autoregulated over a narrow range of mean arterial pressures True / False RPF can be calculated using PAH-since it is not metabolized/synthesized by the kidneys True / false RBF = 1-Hct / RPF True / False © L. Al-Nakkash 2024 23  Blood flow is directly related to the pressure gradient True / False Q= change in P/ R Activation of SNS results in renal vasodilation True / False Vasoconstriction Angiotensin II is a potent renal vasoconstrictor True / False Acts on afferents & efferents With  renal Pa there is an  GFR &  delivery of solutes to the macula densa True / False Tubuloglomerular feedback  solutes   adenosine & vasoconstriction RBF is autoregulated over a narrow range of mean arterial pressures True / False A wide range, between 80-200 mmHg RPF can be calculated using PAH-since it is not metabolized/synthesized by the kidneys True / false RBF = 1-Hct / RPF True / False RBF = RPF / 1-Hct © L. Al-Nakkash 2024 24