Chapter 19 Circulation PDF

Chapter 19: Dominant role of kidney in long term regulation of arterial pressure and in hypertension: the integrated system for pressure control. Short mainly term control, as discussed in Chapter 18, is accomplished by nervous system influence on resistance, capacitance and cardiac pumping acti...

Chapter 19: Dominant role of kidney in long term regulation of arterial pressure and in hypertension: the integrated system for pressure control. Short mainly term control, as discussed in Chapter 18, is accomplished by nervous system influence on resistance, capacitance and cardiac pumping action. The long term control of pressure is controlled by the kidney through a balance in body fluid volume (intake and output). Slide 104 Renal body fluid system for arterial pressure control 1.↑blood volume → ↑BP 2. ↑BP → ↑ urinary output 3. BP returns to normal Pressure diuresis: Increase in output of volume as pressure rises. Too much fluid, blood volume and pressure rise; kidneys excrete excess fluid and return pressure to normal. Pressure NAtriuresis: Figure 19-1 Renal Output Curve “Pressure Diuresis”/ “Pressure Natriuresis” Slide 105 Increase in sodium output as pressure rises. Renal body fluid system for arterial pressure control At 200 mmHg 6-8Xs Normal Renal Function Curve At 100 mmHg = Normal BP at 50 mmHg, urine output = 0 Figure 19-1 Renal Output Curve “Pressure Diuresis”/ “Pressure Natriuresis” Slide 106 At 50 mm Hg, there is no urine output. As AP increases, so does urinary volume output, and sodium output. Note: Infinite Gain Returns to starting point Demonstration of Renal Body Fluid Mechanism in Arterial Pressure Control Sudden increase in blood volume 2X 1500 ml/min to 3500 ml/min 2 ml/min to 24 ml/min Increase cardiac output 12X 100 mmHg to 200 mmHg Figure 19-2 NOTE: In presence of SNS blockade Slide 107 Increase blood volume 2X Increase arterial pressure Increased urine output Instantaneous infusion of 400 ml blood increases cardiac output 2X, AP 2X but increases urine output 12X. Eventually, water loss by increased urine output returns AP, cardiac output and urine output to normal Pressure control by renal-body fluid mechanism ­BP leads to ­output: Restore BP Arterial pressure determined by Intersection of two curves: 1) Renal water and salt output. (same as shown previously, or renal function curve) 2) Net water and salt intake. Equilibrium Point: Intersection of 2 lines (or where output equals input) Figure 19-3 Renal Output Curve “Input = Outtake” (over long periods of time) Infinite Gain: Will always readjust to set point. Slide 108 Two ways to raise arterial pressure and change the equilibrium point 1. Rightward shift of renal output curve - due to kidney abnormality. Also results in a rightward shift of the equilibrium point Increase pressure needed to excrete salt and water. Due to renal abnormality. If shift renal output curve to new level, AP will shift to this new level. Figure 19-4 Slide 109 Two ways to raise arterial pressure 2. The level of water/sodium intake. Increase Intake Note: This diagram assumes no adaptive changes to increased water/sodium Figure 19-4 intake. Slide 110 Two ways to raise arterial pressure It is impossible to change the long-term mean arterial pressure level to a new level without changing (1) the renal output curve (degree of shift of the curve) and/or (2) the level of water/salt intake. But if either changes, BP can be regulated at a new pressure level -or AP level where 2 new curves intersect. Figure 19-4 Slide 111 Acute and Chronic Renal Output Curves When kidneys are functioning normally, the chronic renal output curve is much steeper than the acute curve. How? Figure 19-4 Neural mechanisms Hormonal Mechanisms Slide 112 An increase in resistance doesn’t necessarily mean an increase in AP. P = F x R; AP = Q X TPR AP - arterial pressure Tissue Level Q - cardiac output TPR - total peripheral resistance Instantaneously, an increase in total peripheral resistance does increase AP. But, it does not remain increased. Slide 113 Why? An increase in resistance doesn’t necessarily mean an increase in AP P = F x R; AP = Q X TPR AP - arterial pressure Q - cardiac output TPR - total peripheral resistance Instantaneously, an increase in resistance does increase AP. But, AP does not remain increased. Why? An increase in TPR (outside the kidneys) will not change “equilibrium point” of renal output curve and water/salt intake. Increases in AP will drive water and sodium excretion and return AP to normal within a day. Slide 114 Figure 19-3 An increase in resistance doesn’t necessarily mean an increase in AP Increase TPR Infinite Gain Increase AP Increase water/sodium output “pressure diuresis/natriuresis” Water/salt loss Kidneys, if normal, will respond to high pressure causing diuresis and natriuresis. Slide 115 - An increase in resistance doesn’t necessarily mean an increase in AP: Proof of Principle. AP = Q X TPR AP - arterial pressure Q - cardiac output TPR - total peripheral resistance Clinical conditions where long term TPR is varied. Note: AP is normal. CO or TPR may vary, BUT, kidney excretion of salt and water is normal. Long term TPR or CO is <or > than Normal Figure 19-6 Slide 116 Remember: AP will not change unless the renal output curve is altered. When TPR, everywhere but the kidney, increases, AP will return to the equilibrium point. However, when intrarenal vascular resistance changes at the same time, this shifts the renal output curve to a higher pressure level (a new equilibrium point) and cause hypertension. An increase in renal resistance is the problem, not the increase in total peripheral resistance. Slide 117 Two ways to raise arterial pressure (1) the renal output curve (degree of shift of the curve) (2) the level of water/salt intake. Figure 19-4 Slide 118 How does an increase in fluid volume raise arterial pressure? Local tissue autoregulation: Chptr 17 ­ flow Direct Indirect ­ Nutrient delivery * vasoconstriction Metabolic theory Figure 19-7 Slide 119 Importance of salt in renal body fluid schema for AP regulation. Salt intake is more likely to raise AP than water intake. A. Increased salt intake increases extracellular fluid osmolality which stimulates thirst center in brain to increase water intake. B. Increased osmolality stimulates release of antidiuretic hormone which increases water reabsorption along the nephron. ADH = Vasopressin Both processes increase extracellular fluid volume. * Amount of salt the main determinant Slide 120 of extracellular fluid volume Û Salt intake Û osmolality ÛThirst Û ADH release ÛWater intake Û salt/water retention (Ü salt/water excretion) Volume Loading Hypertension More rapid and greater increase in MAP. Learned to Tolerate salt water. SALT Removal of 70% renal mass. SALT Tap water, BP returns to normal. Figure 19-8 This is an example of how increasing the extracellular fluid volume can produce hypertension. Slide 121 Salt solution fails to quench the thirst. Drink more. BP increases. Volume Loading Hypertension SALT Figure 19-8 Slide 122 Removal of 1/3 of left kidney followed by removal of right kidney elicits small increase in AP. Removing renal mass decreases the number of functional nephrons (functional unit of kidney) and thus compromises kidney’s ability to unload salt and water. Volume Loading Hypertension SALT Figure 19-8 Slide 123 Û salt/water intake When given a salt solution to drink instead of water, the animals drink 2-4x as much because the salt water does not satisfy thirst. Animals develop volume-loading hypertension. Volume Loading Hypertension Figure 19-8 Slide 124 AP increased because the reduced renal mass blunted the ability of the kidney to excrete sodium and water. Thus water and sodium accumulated and caused hypertension Volume Loading Hypertension 1. Shifted pressure natriuresis curve Both determinants of Long-term BP regulation were increased. Slide 125 2. Increased salt and water input Changes in circulatory function during progressive development of volume loading hypertension Conditions: • Reduced renal mass. • Salt loading-sustained. How is this different from the previous slide? 1) Sustained increase in salt loading. 2) Figure 19-9 A closer look at the circulatory events leading to volume-loading hypertension (EFV, BV, TPR) Slide 126 Changes in circulatory function during progressive development of volume loading hypertension INITIAL Acute Response Increase extracellular fluid volume Increase blood volume Increase cardiac output Autoregulatory increase in TPR Increase AP Baroreceptor activation Figure 19-9 Slide 127 Initiate Salt Loading Decrease SNA/Increase PNA Changes in circulatory function during progressive development of volume loading hypertension INITIAL Acute Response Increase extracellular fluid volume Increase blood volume Increase cardiac output ↑ Flow Autoregulatory increase in TPR ↑ TPR Increase AP Vessel compensation Baroreceptor activation Figure 19-9 Slide 128 Initiate Salt Loading Decrease SNA/Increase PNA Changes in circulatory function during progressive development of volume loading hypertension Acute Response Increase extracellular fluid volume Increase blood volume Increase cardiac output Autoregulatory increase in TPR BUT…Initial ↓ in TPR Increase AP to prevent ↑ BP Baroreceptor activation Figure 19-9 Slide 129 Initiate Salt Loading What accounts for small drop in TPR? Resets in 2 to 4 days Decrease SNA/Increase PNA Changes in circulatory function during progressive development of volume loading hypertension Myogenic Metabolic Chronic Response Secondary Baroreceptors reset -- Progressive increase in TPR due to autoregulatory changes (vasoconstriction). ↓ECFV and BV Decrease in cardiac output Increase arteriolar resistance Decreased capillary hydrostatic P Figure 19-9 Slide 130 Initiate Salt Loading Increase AP Increase renal salt and water excretion Decrease extracellular fluid and blood volume Changes in circulatory function during progressive development of volume loading hypertension Myogenic Chronic Response Metabolic Final Baroreceptors reset -- Progressive increase in TPR due to autoregulatory changes (vasoconstriction). ↓ECFV and BV Decrease in cardiac output Increase arteriolar resistance Decreased capillary hydrostatic P 1. Shifted pressure natriuresis curve Figure 19-8 Slide 131 Initiate Salt Loading 2. Increased salt and water input Increase AP Increase renal salt and water excretion Decrease extracellular fluid and blood volume Importance of the renin-angiotensin system (RAS): Role in pressure control and hypertension Renin-Angiotensin System Figure 19-7 (JG cells in kidney) Renin - Angiotensin system activated by a fall in pressure. is Renin is an enzyme released by kidney. Volume-loading based hypertension Ang II stimulates water and sodium reabsorption in the kidney. ↑ECFV Slide 132 ↑TPR Importance of renin-angiotensin system: Hemorrhage. Severe hemorrhage can lower arterial pressure to 50 mm Hg. If the RAS is blocked, AP doesn’t increase much further. When the RAS is intact, it is able to buffer the drop in AP. Increase vasoconstriction. Figure 19-11 Normal role of RAS is to protect against falls in pressure Slide 133 Importance of renin-angiotensin system: Effect of angiotensin II (Ang II) in the kidney How does AII affect the kidney? Ang II is the main effector in the Renin Angiotensin System 1. Effect on salt and water transport (vasoconstriction) a) Constriction of the renal arterioles decreases BF through the kidney so less blood is filtered. b) Direct effect on tubular reabsorption. Slows flow so more fluid can be reabsorbed and direct effect on tubular cells themselves. 2. Stimulates aldosterone release which increases salt and water reabsorption in the kidney. Aldosterone increases sodium and water reabsorption in tubules. Thus, less excreted. Slide 134 Importance of renin-angiotensin system: Effect of angiotensin on renal output curve (1) (2) Shift renal output curve + captopril: blocks formation of ANG II to equal zero level of Ang II in blood Normal + ANG II infusion to equal 2.5X above normal level in blood NORMAL Conditions Shift in renal output curve Absorb moreExcrete less. Figure 19-13 Figure 19-12 (1) Angiotensin II influences position of renal output curve. (2) Ang II helps control BP in response to changes in salt intake. Slide 135 Importance of renin-angiotensin system: Effect of angiotensin on renal output curve Endogenous Ang II blocked Ang II infusion 1.0 Elevated Ang II causes rightward shift. Direct and indirect actions Decreased AII leftward shift. causes High AII--kidney excretes less sodium and water (reabsorbs more) at a given AP. Figure 19-12 Slide 136 Importance of renin-angiotensin system: Effect of angiotensin on renal output curve Lets assume subject starts at AP = 115 1.0 NORMAL Conditions New salt/water intake curve Adaptive responses have not yet taken place. Rightward shift of renal output curve Slide 137 Changes in arterial pressure during chronic changes in sodium intake – Importance of the renin angiotensin system. Slide 138 Chronic Hypertension Slide 139 Chronic Hypertension What is hypertension? Slide 140 Chronic Hypertension Damaging effects of hypertension…. cardiac high AP = high afterload vascular injury in brain stroke vascular injury in kidney renal injury Slide 141 Primary essential hypertension Essential” – means is of unknown origin Most common form -- 90-95% Usually accompanied weight gain, sedentary lifestyle Characteristics: increased cardiac output (to feed extra adipose) increased sympathetic nerve activity elevated Ang II and aldosterone renal-pressure natriuresis mechanism impaired (i.e. kidneys don’t excrete sodium/water adequately) Obesity thought to be main mediator [ ­CO, ­SNS, ­Angiotensin II] Slide 142 Primary essential hypertension Characteristics: Increase in CO Increased SNS activation (obesity) Increased ANG II and aldosterone Impaired Pressure/Natriuresis mechanism. Common treatment for hypertension: 1. Vasodilator therapy---increase renal blood flow (Block SNS, Block RAS, relax VSMC) 2. Diuretic therapy--increase renal salt and water excretion (decrease reabsorption) Slide 143 Hypertension Volume loading and vasoconstriction: Coarctation of the aorta = upper blockage of the aorta. Leads to an increase in AP in upper body that is 40 to 50% > than that in lower body. Preeclampsia Acute Neurogenic hypertension Genetic Slide 144 Clinical Correlation Why knowing your patients blood pressure is so important. Patients cardiovascular health can be an issue during treatment. • Patients with hypertension are at increased risk of developing adverse effects in a dental office. • Know your patients cardiovascular history. Keep it upto-date. • Measure BP for every new patient, and for each visit. Dentistry Local anesthesia can affect blood pressure. • Local anesthesia is an important part of dental work but many anesthetics include epinephrine, which helps prolong the numbing effect but also is a vasoconstrictor which can elevate blood pressure. • In patients with chronic systemic diseases, BP measurement should be carried out during more complicated dental interventions as oral surgery, restorative treatment complicated with longer sessions, placing dental implants, and periodontal surgery. Measuring your patients blood pressure could save their life. • The symptoms for hypertension are subtle and often go unnoticed. A blood pressure screening check is often the first indication of a problem and that is why blood pressure screening in a variety of healthcare settings including the dental office is so important. Clinical Correlation Primary essential hypertension “Sodium-loading renal function curve” The basic cause of essential hypertension is the inability of the kidneys to excrete an adequate volume of urine at normal arterial pressure. LONG TERM: Rightward shift: Hypertension due to renal abnormality Salt sensitive: High salt intake exacerbates the hypertension. = Change in slope. Figure 19-15 Slide 145 Difference due to structural or functional? Primary essential hypertension “Sodium-loading renal function curve” The basic cause of essential hypertension is the inability of the kidneys to excrete an adequate volume of urine at normal arterial pressure. Therefore, fluid accumulates in the body until the pressure rises high enough to balance fluid output with fluid intake. This fluid balancing act is an infinite gain feedback system for controlling arterial pressure to a very precise level determined by the kidneys. Infinite gain allows the kidney mechanism to dominate the other pressure control mechanisms for long-term pressure control. Figure 19-15 Slide 146 Û Salt intake Slide 147 This system is very sensitive. Small changes in volume and pressure cause big changes in renal output. Û Plasma osmolality ÛThirst Û Water intake **magnitude of change is so small, this may not be detected clinically** Û Cardiac Output** Û Vascular resistance** Û ADH release ÛWater retention (Ü water excretion) ÛExtracellular fluid volume** ÛBlood volume** - Û Arterial Pressure** Inhibit Ang II release ÛDiuresis/Natriuresis (remove excess volume) Leftward shift of renal output curve (kidney less effective at retaining Na+/water for any given pressure) Integrated arterial pressure regulation Arterial pressure is regulated by several interrelated systems. Figure 19-16 Slide 148 Integrated arterial pressure regulation Arterial pressure is regulated by several interrelated systems. Early Onset- Neural baroreceptors chemoreceptors CNS ischemic (drop in AP below 60 mmHg) Figure Figure19-16 19-16 Slide 149 Integrated arterial pressure regulation Arterial pressure is regulated by several interrelated systems. Intermediate Onsetrenin angiotensin stress relaxation (Distensibility) capillary fluid shift: ↓Cap Fluid Press ↑ reabsorption of fluid from tissues through the capillary membranes and into the circulation Figure 19-16 Figure 19-16 Blood Volume Slide 150 Integrated arterial pressure regulation Arterial pressure is regulated by several interrelated systems. Late Onsetrenal-blood volume pressure control (↑ output as pressure rises) Figure 19-16 Figure 19-16 Slide 151