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132 Cards in this Set
- Front
- Back
What is Pressure diuresis?
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The doubled increase in renal water output when arterial blood pressure rises only a few mm Hg.
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What is Pressure natriuresis?
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The doubled increase in renal SALT output when arterial blood pressure rises only a few mm Hg.
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What is meant by the infinite feedback gain principle for renal control of longterm bp?
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Whenever BP increases or decreases, the intake/output of water and salt will respond to return BP and levels to EXACTLY the equilibrium point.
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What is the equilibrium point on the Renal output curve?
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The point where normal sodium and water intake and output intersect and are equal.
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What is the MAP for normal renal intake/output (equilibrium point)?
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100 mm Hg.
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2 determinants of the longterm arterial pressure level:
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1. Degree of pressure shift of Renal Output curve for H2O/salt
2. Level of water/salt intake line. |
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What happens if either of the determinants of longterm MAP change?
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BP will be regulated at a new level - the new equilibrium point.
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What is MAP equal to?
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MAP = TPR x CO
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What happens when TPR increases normally?
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MAP increases, kidneys function normally, and MAP returns to normal within a few days.
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Why doesn't an increase in MAP (caused by increased TPR) cause the equilibrium point for longterm BP control to shift?
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B/c the resistance in the kidneys does not change even tho it does everywhere else; rather Pressure Diuresis/Natiuresis occurs.
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What provides short term control of arterial blood pressure?
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Sympathetic nervous system
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How does the SNS control BP?
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By effecting
-TPR and capacitance -Cardiac contractility |
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How does the body control arterial pressure in the longterm?
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By regulating body fluid volume
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What determines the body fluid volume?
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The balance between fluid intake and output
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What is the Renal-Body fluid system for arterial pressure control?
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Simple:
When the body has to much ECF the blood volume and arterial pressure rise. |
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How does rising arterial pressure affect the kidney?
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Causes it to excrete excess ECF to return pressure back to normal.
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Pressure Diuresis:
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Doubling of renal water output in response to increase in arterial pressure
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Pressure natriuresis:
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doubling of renal salt output in response to increase in arterial pressure
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How has the renal-body fluid arterial pressure control system been refined over time?
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By the addition of the renin-angiotensin mechanism
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Renal output in a human at arterial pressure of 50 mmHg:
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essentially zero
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Renal output at BP = 100
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normal
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Renal output at BP = 200
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6-8 x normal
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As urine output increases with increasing BP what else increases?
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Sodium output - almost equally
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3 variables that increase when you block the nervous pressure control mechanisms in dogs and then increase blood volume by infusing 400 mL blood:
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-Cardiac output increases by 2X
-Urinary output increases by 12X -MAP increases to 115mmHg above normal |
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What is the result of the increased urinary output after increasing a dog's blood volume?
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CO and MAP both return to normal within one hour
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What do we learn from the dog expirement?
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The renal system is very capable of controlling MAP by changing volume output
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How is renal regulation of MAP analysed?
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By looking at the Renal Output Curve
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What are the axes of the renal output curve?
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X = arterial pressure
Y = intake/output of salt and water times normal |
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What does the equilibrium point on the renal output curve represent?
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The MAP where salt/water output and intake are equal
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What happens at MAP above the equilibrium point?
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Water/salt output will increase to decrease MAP back to the equilibrium point
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What will happen below the equilibrium point?
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Water/salt will be retained until the MAP goes back up to equilibrium point.
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Where is the normal equilibrium point for the renal output curve?
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At 100 mm Hg - intake/output are 1
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What happens if MAP goes up to 150 mm Hg?
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Renal output increases to 3x normal until MAP goes back down
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What happens if MAP goes down to 50?
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Renal function is essentially zero
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2 ways MAP can be increased:
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1. Shift renal function curve to right toward a higher MAP level
2. Increase level of salt/water intake |
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What causes the renal output curve to shift to the right?
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Abnormal renal functioning
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We know that MAP = TPR x CO; doesn't that control MAP?
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No; not in the long term.
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What happens to MAP in the longterm if total body TPR is greatly elevated?
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It will change CARDIAC OUTPUT
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What happens to CO as TPR increases?
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CO decreases
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What controls the setpoint of MAP?
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Renal function
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Why doesn't increasing TPR increase MAP?
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It does; but if the kidneys are functioning normally, then MAP will go back down in the longterm.
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How is it that an increase in TPR and MAP doesn't increase the equilibrium setpoint for MAP on the renal function curve?
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MAP increases everywhere EXCEPT in the kidney - there, pressure diuresis and natiuresis occur to reduce blood vol and MAP back to normal.
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How does increasing ECF increase MAP directly?
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1. Increase ECF
2. Increase blood volume 3. Increase Psf 4. Increase VR to heart 5. Increase CO 6. Increase MAP |
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How does increasing ECF increase MAP indirectly?
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-Same steps to increase CO
-CO indirectly increases MAP by the autoregulation that responds to it to increase TPR; that then increases MAP. |
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so CO affects MAP in what two ways?
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1. Directly increases MAP
2. Indirectly increases TPR via autoregulation -> increases MAP |
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2 reasons for why ECF volume increases as salt accumulates in the body:
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1. Incr Salt -> incr fluid osmolality -> stim thirst center in brain -> drink more H2O -> ECF volume increases
2. Incr osmolality -> incr ADH release -> kidneys reabsorb more water/Na from renal tubules -> decr urine output, incr ECF volume |
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Where is ADH produced?
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Hypothalamic-posterior pituitary gland
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So what is the main determinant of ECF volume?
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The amount of salt that accumulates in the body.
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What 5 variables change in response to volume-loading hypertension?
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-ECF
-Blood volume -CO -TPR -MAP |
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What is the basic cause of hypertension when sodium and water intake are markedly increased on day 0?
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Increased cardiac output!
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How does TPR initially respond to volume loading at day 0? Why?
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It initially decreases -13% because of the baroreceptor acute response to decrease MAP.
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How does TPR change over the next 14 days?
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It increases secondarily as the autoregulation mechanism returns CO almost to normal.
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What are the longterm results at day 14 after volume-loading?
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-CO is almost back to normal (only increased by 5%)
-TPR is mrkdly increased by 33% -MAP is elevated by 40% |
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What is it that causes MAP to stay elevated after volume loading?
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Decreased renal functioning due to decreased renal mass; it changed the setpoint by shifting the renal function curve to the right.
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How is increased TPR related to hypertension?
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It does NOT cause it, but is a result of increased CO and the autoregulatory response trying to decrease it back to normal.
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What are the longterm effects of volume loading HTN on blood volume and ECF volume?
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Not that markedly elevated; thats because the MAP equilibrium point was increased by shifting the renal output curve to the right. That's the whole problem...
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What levels of systolic and diastolic bp define HTN?
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-Sys BP of >135
-Dia BP of >90 |
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What is the response of TPR to acute increase in blood flow and MAP?
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It increases so that bloodflow doesn't increase proportionately to the increase in MAP - to protect the vessels.
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How does TPR change in chronic hypertension?
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Even more to keep bloodflow lower as MAP keeps getting higher.
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How does TPR continue to increase with chronic HTN?
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By increasing the number of vessels (angiogenesis) and thickness of the vessel walls.
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What is the chronic renal function curve determined by?
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A balance of intrinsic and extrinsic factors
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What are the 5 intrinsic factors within the kidney that determine the chronic renal function curve?
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1. Physical factors (hydrostatic pressure)
2. Ang II 3. Prostaglandins 4. Kinins 5. NO from the renal medulla |
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What 5 extrinsic factors determine the chronic renal function curve?
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1. SNS
2. Ang II 3. Aldosterone 4. Vasopressin (ADH) 5. ANP |
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Which factor that controls the chronic renal function curve is most important? Why?
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Ang II by far - because it is the key controller of the body's adjustment to changes in water/salt intake and output.
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The kidney's 2 mechanisms for controlling MAP are:
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1. Changing ECF volume
2. RAS |
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What makes the RAS activate?
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Decreased MAP - thekidney dects falling arterial presure in its afferent arteriole, and releases RENIN.
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Where is Renin made and stored?
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In juxtaglomerular cells in the kidney.
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What are JG cells and where are they located?
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Modified smooth muslce cells in the walls of the afferent arterioles just proximal to the glomeruli.
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What happens to the renin released in response to decreased MAP?
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It enters the blood and circulates throughout the body; some remains locally to initiate intrarenal functions.
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What does renin do?
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Acts on Angiotensinogen to release 10 AA peptide called Ang I
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What does Ang I do?
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Mild vasoconstrictor but not much.
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How long does renin circulate?
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Persists in blood for 30 min to 1 hr to cause more Ang I formation
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What happens to Ang I? By what enzyme?
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It gets 2 AAs split from it to form Ang II - done by ACE.
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Where is ACE located?
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Lung vessel endothelium
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2 principal actions of Ang II:
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1. Vasoconstriction all over the body
2. REnal retntion of salt/water |
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How long does Ang II persist?
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only 1-2 min
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What inactivates Ang II?
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Angiotensinase
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Where does most of the vasoconstriction caused by Ang II occur?
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In arterioles (much less in the veins).
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Result of vasoconstricting arterioles:
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Increased TPR therefore increased MAP.
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What happens when you induce hemorrhage enough to acutely decrease MAP to 50 mm Hg normally?
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Pressure will rise back up to 83 mmHg when RAS is functional.
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What happens when you induce hemorrhage enough to acutely decrease MAP to 50 mm Hg when RAS is nonfunctional??
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Pressure will rise back up only to 60 mmHg
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How long does it take the RAS to become fully active in acute hemorrhagic conditions?
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About 20 min
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2 Ways that Ang II causes the kidneys to retain salt/water:
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1. Direct action on kidneys to cause salt/H2O retention
2. Causes adrenals to secrete ALDOSTERONE - which does same. |
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Function of Aldosterone:
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Increased water and salt reabsorption by kidney tubules
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How does the circulation of Ang II effect the renal function curve?
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It causes MAP control setpoint to be at a higher MAP than normal (shifts the curve to the right).
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How does Ang II directly cause water/salt retention in the kidney (4 ways)?
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1. Constricts renal arterioles -> reduced bloodflow
2. Reduces post-glom cap pressure -> incr tubular fluid reabsorption 3. Decreases GFR 4. Directly causes tubular epithelium to increase Na reabsorption |
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Ang II is a powerful stimulator of:
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Aldosterone secretion by adrenal glands
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Important effect of Aldosterone is:
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sodium reabsorption by the distal tubules
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Result of increased sodium reabsorption:
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Increased ECF volume, water retention, long term elevation of MAP.
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At what MAP is the renal function curve equilibrium point if Angiotensin II level is zero?
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75 mm Hg
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At what MAP is the renal function curve equilibrium point if Angiotensin II level is 2.5X the normal level?
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115 mm Hg
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What would cause the renal output curve to shift to the left and make MAP 75?
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Captopril - ACE inhibitors
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What would cause the renal output curve to shift to MAP setpoint of 115?
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-Direct effects of Ang II on the kidney
-Indirect effects acting through aldosterone |
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what is the RAS especially important in allowing us to do?
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Eat more or less salt without really altering MAP.
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How does the RAS let us eat more salt? (7 steps)
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1. Increased salt intake
2. Increased ECF vol 3. Increased MAP 4. Decreased Renin / Ang II 5. Decreased H2O/Salt retention 6. Return ECF vol to normal 7. Return MAP to normal |
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How much does MAP rise in response to a 50-fold increase in salt intake?
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No more than 4-6 mm Hg.
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How much does MAP rise in response to the same salt intake increase when RAS is blocked?
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MAP rises to 10X normal - like 50-60 mm Hg higher
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How do Ang II levels change with increasing salt intake?
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They decrease
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How does the equilibrium point of the renal function curve change with increases in salt intake?
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The curve does NOT shift to the right, but becomes steeper so that MAP is kept constant in spite of increased salt intake.
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How soon does the direct action of Ang II on total body vasoconstriction take to occur?
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Seconds
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How long does the indirect effect of Ang II to increase aldosterone take to occur?
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Period of days
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What is Goldblatt hypertension?
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Induced HTN caused by removing one kidney and clamping the other renal artery to vasoconstrict it.
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What is the kidney's response to a goldblatt clamp?
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It senses reduced pressure in the renal artery beyond the constrictor, so thinks it should increase RAS to increase MAP.
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How soon does Renin increase after putting the goldlbatt clamp on?
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Within seconds - minutes.
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What happens to MAP after placing the goldblatt clamp?
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Ang II increases MAP DRASTICly over the first hour, then it continues to increase gradually over the next several days.
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When does renin secretion peak and return to normal in Goldblatt hypertension?
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Peak - within first hour
Return to normal - in 5-7 days |
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What causes renin secretion to return to normal when the goldblatt clamp is still on the kidney?
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Ang II vasoconstriction and salt/water retention increased MAP, which increased renal arterial pressure, so Renin did not need to remain high.
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In order to get the renal artery pressure back up (beyond the clamp), what had to happen to the rest of body MAP?
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It increased to higher than normal levels - hypertension.
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Why does the kidney care so much about having high enough pressure in the renal artery?
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So that it can have adequete urine output - it doesn't care what MAP is, just its own.
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2 increases in MAP are seen in goldblatt htn; what are they?
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1. Direct effect of ANGII causing vasoconstriction
2. Indirect effect of Ang II and Aldosterone to incr Salt/H2O retention. |
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What happens to the renal output curve in Goldblatt hypertension?
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It shifts to the right
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Why does the RFC shift to the right in goldblatt HTN?
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Because this is salt-insensitive - salt intake levels have not changed, but renal arteriole pressure has.
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What happens to long term MAP:
-if you increase TPR -if you increase renal artery P |
TPR - will not increase MAP
Renal artery P - will increase MAP |
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How is mass balance of sodium and water achieved?
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By reflex and hormonal response that effect the kidney
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5 Reflex/hormonal responses to increased salt/water intake:
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1. SNS activity decreases
2. ADH secretion decreases 3. Renin/angiotens system decr. 4. Aldosterone decreases 5. ANP INCREASES |
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What type of feedback control is exhibited by the reflex and hormonal responses?
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Proportionate - finite; they adapt and are good only for acute short-term responses.
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What type of MAP controller is INFINITE feedback control?
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The Renal-Body fluid controller - that is just the way that the kidney increases output in response to increase MAP and vice versa.
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What is primary hypertension?
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Aka essential; the cause is unknown but there are strong hereditary factors and obesity associations.
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4 characteristics of primary HTN in obese patients:
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1. Increased CO
2. Increased SNS activity 3. Increased AngII/aldosterone levels 4. Impared natriuresis |
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Why is natriuresis impaired in obese HTN patients?
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Because the increased SNS activity causes increased renin release, increased AngII and Aldosterone, which PROMOTE salt/water RETENTION.
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What is the difference between salt-sensitive and non-salt-sensitive HTN?
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In a nonsalt-senstv HTN patient 3.5X normal salt intake will not change MAP; it will increase it in the salt-sensitive patient.
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Why are some primary HTN patients salt-sensitive and some are not?
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Due to functional differences in their kidneys - loss of nephrons or abnormal RAS functioning.
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2 general drug classes used for treating HTN:
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1. Vasodilators (to increase renal blood flow)
2. Natriuretic drugs to decrease tubular reabsorption of salt and water. |
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How is the difference between salt-sensitive and nonsalt-sens HTN exhibited on the renal function curve?
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Both curves are shifted to the right, but only the salt-sens curve will show an increased MAP when salt intake increases.
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What 3 mechanisms have the most acute response to changes in blood pressure?
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1. baroreceptors
2. Chemoreceptors 3. CNS ischemic response |
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3 actions of the acute pressure change responses:
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1. Vein constriction to incr VR
2. Incr HR and contractility 3. Periph arteriole constriction (incr TPR) to slow bloodflow and keep in capillaries longer |
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Within what timeframe do the acute response mechanisms operate?
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Seconds to minutes
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What 3 mechanisms have intermediate responses to changes in blood pressure?
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1. RAS
2. Capillary fluid shift 3. Stress relaxation |
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How does capillary fluid shift respond to increased MAP?
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More fluid shifts from CAPs -> tissues
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When are the intermediate mechanisms most active?
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Within 30 min to several hours
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What is the longterm responder to changes in MAP?
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The renal-blood volume pressure control response
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Which pressure controller mechanisms have the highest feedback gain?
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-Renal blood vol pressure control -> infinite
-Ischemic CNS response -Baroreceptors -Chemoreceptors |