this unit talks about the different mechanisms used by the kidney to maintain blood pressure. in contrast to the short term regulation of blood pressure, which occurs in seconds or minutes when the baroreceptors in the aortic and carotid sinuses trigger a sympathetic pathway that increases cardiac output and decreases total peripherial resistance (recall from the vascular regulation lecture), the long term regulation of blood pressure occurs on the order of days to weeks and involves stimulation and inhibition of hormone systems which regulate fluid excretion in the kidney.
two conditions that are subject to regulation by the kidney are introduced: hypervolemia and hypovolemia. hypovolemia is the loss of body fluids via hemorrhage, dehydration, etc.; this is reflected in a decreased blood volume, which is sensed at both the cardiac baroreceptor level and also at the JGA apparatus. the sympathetic nervous response is to constrict the afferent and efferent arterioles (as well as ADH release in extreme cases), while JGA stimulates the renin-angiotensin system, the net effect being increased reabsorption. congestive heart failure or aortic stenosis can incorrectly stimulate a correction for hypovolemia: the decreased blood flow in these conditions will result in the JGA responding as if there is hypovolemia and cause excess reabsorption, leading to systemic edema. hypervolemia is the opposite condition in which there is excess fluid volume (due to fluid or salt intake). the body's response to this is to inhibit the renin-angiotensin system, and activate atrial natriuretic peptides, as well as pressure natriuresis. all three of these responses entail mechanisms that increase excretion and decrease reabsorption.
the next section talks about hypertension, which is essentially a chronically high blood pressure, and what it is caused by. "primary" hypertension seen in 90% of all cases of high blood pressure and usually involves the "blunted pressure natriuresis" phenomenon. pressure natriuresis is normally an increase in the excretion of water and solute in response to increased arterial pressure via a dilation of the vasa recta, which shifts the starling forces in a direction that inhibits reabsorption. excess angiotensin II and salt can oxidatively damage the vasa recta, not allowing it to vasodilate as easily; this means that the pressure natriuresis compensation begins at a higher pressure than usual (displayed a shifting right of the solute excreted vs. arterial pressure curve). secondary hypertension can be caused by a variety of conditions such as renovascular hypertension or renal parenchymal disease, the end result being salt retention and a rightward shifting of the pressure natriuresis curve. in salt-sensitive individuals with hypertension, increasing salt intake can further increase the pressure at which pressure natriuresis begins, due to the damage to the vasa recta and peripheral tissues that occurs in these individuals.
the progression of hypertension can be divided into three phases: phase I is characterized by a persistent excess of angiotensin II and sympathetic activity. phase II is characterized by the chronic vasoconstriction resulting from high angiotensin II, which begins to cause subtle renal injury and an increase in blood pressure/volume. phase III is when the pressure natriuresis occurs, lowering the blood pressure back down to normal, but resulting in a hypertensive kidney.
the next section looks at the regulation of the reabsorption of K+ in the kidney. control over K+ is important because most of the K+ in the body is intracellular, rather than in the extra cellular fluid- thus small changes in intake or excretion of potassium can have large effects. Most of the K+ reabsorption happens in the proximal tubules and is not controlled by hormone or ion levels. However, in the collecting duct, potassium reabsorption can depend on relative ion levels (the alpha-intercalated cells excrete H+ in exchange for K+ in response to a K+ deficiency) or hormone levels (the principal cells have sodium / potassium pumps that are upregulated by aldosterone)
the last section looks at diuretics, which are substances that increase urine output generally by blocking sodium reabsorption in different parts of the nephron, or by increasing the osmolality of the fluid in the lumen of the tubule (and therefore holding the water in the lumen to be excreted). osmotic diuretics such as glucose or sucrose increase osmotic retention in the proximal tubule, and also increase K+ secretion in the distal tubule due to the larger concentration gradient between the lumen and the interstitial space. loop diuretics block solute reabsorption in the thick ascending tubule and therefore osmotically pulls more water into the lumen to be excreted. thiazide is another diuretic that has the same effect on the distal convoluted tubule. caffiene is a diuretic that blocks reabsorption in both the proximal and distal tubule. all of these diuretics mentioned thus far have the potential to induce hypokalemia, a deficiency of potassium, because the hypovolemia that could develop might trigger aldosterone release, which would increase K+ excretion. a "potassium sparing" diuretic is an aldosterone inhibitor, which simply blocks the action of the sodium/potassium pump in the principal cells, leaving sodium in the lumen which increases osmolality and pulls water to be excreted.
questions
1. blood pressure is a measure of how effectively...
2. three factors that are needed to maintain adequate blood pressure...
3. blood volume is regulated by...
4. describe short term regulation of blood pressure.
5. describe long term regulation of blood pressure.
6. what is the timescale for the short term regulation of blood pressure?
7. what is the timescale for the long term regulation of blood pressure?
8. how is blood volume monitored?
9. what is the body's response to hypovolemia?
10. how can congestive heart failure or stenosis of the arteries lead to pulmonary edema?
11. what is the body's response to hypervolemia?
12. what is the difference between the response of the JGA and ANP/pressure natriuresis to hypervolemia?
13. describe what happens when pressure natriuresis is "blunted".
14. most cases of primary hypertension are due to...
15. most cases of secondary hypertension are due to...
16. what occurs in renovascular hypertension?
17. what occurs in salt-sensitive hypertension?
18. how does the pressure natriuresis curve shift in salt sensitive hypertension?
19. describe the two factors that affect the vascular tone of the vasa recta.
20. what effect do angiotensin II and salt have on the vasa recta?
21. what are the two ways in which damage to the vasa recta can augment vasoconstriction?
22. what are some other risk factors for hypertension?
23. what are the characteristics of phase 1 of primary hypertension?
24. what are the characteristics of phase 2 of primary hypertension?
25. what are the characteristics of phase 3 of primary hypertension?
26. what are hypo and hyperkalemia and how does the body respond to these conditions?
27. describe the reabsorption of potassium in the proximal tubules.
28. where is reabsorption of potassium hormonally regulated?
29. what are alpha-intercalated cells and what do they do?
30. what are principal cells and what role do they play in the regulation of reabsorption of potassium?
31. how does excess and deficient K+ affect the principal cells?
32. how do diuretics work?
33. how does heart failure lead to edema?
34. how do osmotic diuretics work?
35. most common treatment of hypertension is...
36. what does thiazide do?
37. describe the mechanism of the treatment of hypertension with thiazide and ACE inhibitor.
38. what do loop diuretics do and what are some examples of them?
39. caffeine causes diuresis by...
40. why is an aldosterone inhibiting diuretic called a potassium sparing diuretic?
answers
1. the vascular system perfuses organs with blood.
2. integrity/strength of vessels, compliance of blood vessels, and adequate blood volume (5L)
3. cardiac output, peripheral resistance,
4. baroreceptors sense changes in mean arterial pressure and adjust cardiac output and total peripheral resistance accordingly.
5. baroreceptors and salt detectors initiate neuroendocrine response that can adjust blood volume (and therefore blood pressure) by altering reabsorption of fluid in kidney.
6. response within seconds and can last for minutes.
7. days to weeks.
8. via baroreceptors in arteries, veins, as well as the juxtaglomerular apparatus.
9. baroreceptors and JGA cells trigger renin / angiotensin system which increases reabsorption, and in severe cases the CNS is triggered to release ADH which also increases reabsorption.
10. both of these conditions lead to a decrease in blood flow to the kidney, which triggers mechanisms that increase reabsorption, increasing fluid volume excessively and causing circulatory congestion and pulmonary edema.
11. inhibiting the RAAS system, production of atrial natriuretic peptides, and stimulating pressure natriuresis.
12. JGA involved mainly in suppressing renin-angiotensin system, which then decreases reabsorption. ANP/pressure natriuresis is more involved in increasing GFR (but still subject to glomerulotubular feedback)
13. blunted pressure natriuresis can be caused by damage to the vasa recta that reduces its ability to synthesize NO. this leads to higher blood pressures required to produce the same vasodilation, effectively reducing excretion and shifting the pressure natriuresis curve (sodium excretion vs. blood pressure) to the right.
14. high blood pressure, and blunted pressure natriuresis.
15. renal diseases that result in salt retention such as renal parenchymal disease, renovascular disease, pheochromocytoma, cushing syndrome.
16. hardening of the renal arteries decreases renal blood flow, eliciting the RAAS system and secretion of angiotensin II which constricts the arteries and shifts the pressure natriuresis curve to the right.
17. increased salt intake in salt-sensitive individuals causes short term increases in blood pressure.
18. the curve shifts to the right and the slope decreases.
19. angiotensin II released by local vessels and tubules cause pericytes around vasa recta to constrict by increasing intracellular levels of Ca2+. NO produced by thick ascending loop causes pericytes to relax.
20. creating reactive oxygen species that damage vasa recta via oxidative stress.
21. by exacerbating RAAS vasoconstriction and inhibiting vasodilation by NO, prostaglandins, dopamine.
22. genetics, age, obesity, insulin resistance
23. persistent excess angiotensin II and sympathetic nervous activity.
24. chronic vasoconstriction due to the angiotensin/NO balance lead to subtle renal injury which leads to sodium retention and increased blood volume/pressure.
25. pressure natriuresis curve shifts to the right; blood pressure rises and salt excretion increases.
26. hypokalemia is a deficiency of potassium which causes muscle weakness and twitches, and is compensated by increased K+ reabsorption. hyperkalemia is excess potassium which causes cardiac arrhythmias and excitability; compensated by increased K+ secretion.
27. 67% of potassium is reabsorbed in proximal tubules, 20% in thick ascending limbs. neither of these areas are regulated by hormone or ion levels.
28. in the distal tubule and collecting duct
29. cells in the collecting duct that actively reabsorb K+ via a K+/H+ ATPase pump.
30. principal cells make up 90% of the collecting duct epithelium and contain ATPase pumps that exchange K+ for Na+. aldosterone can upregulate these pumps, which increases Na+ and therefore water reabsorption, as well as increasing K+ excretion.
31. in K+ excess, ATPase pumps in principal cells are upregulated to increase excretion of K+. in K+ deficiency, aldosterone release is inhibited, causing more K+ to be retained within the body.
32. by inhibiting sodium reabsorptions at different points along the nephritic tubule.
33. heart failure causes a drop in arterial pressure which via the RAAS system induces higher fluid reabsorption in the kidney, causing a higher venous pressure. higher venous hydrostatic pressure causes fluid to leak out into the extracellular space, causing edema.
34. solutes such as glucose, sucrose, mannitol, corn silk, are filtered but not reabsorbed, leading to a higher solute concentration in the tubule and thus less reabsorption of water.
35. thiazide diuretics and ACE inhibitor
36. inhibits Na,Cl reabsorption in distal tubules leading to more water excretion
37. thiazide blocks the Na,Cl reabsorption in the distal tubules, leading to more water excretion. this could in theory produce a hypovolumic state, which would trigger aldosterone release and therefore K+ excretion. thus ACE inhibitors are used to block the formation of angiotensin II and counter K+ secretion.
38. loop diuretics block reabsorption of Na, Cl, K in the ascending loop of henle and thus increase water excretion. examples are: Lasix, ethacrynic acid, bumetanide.
39. inhibiting Na+ reabsorption from proximal and distal tubules.
40. it inhibits aldosterone release, which increases Na+ excretion in the water and retains more K+.
Showing posts with label aldosterone. Show all posts
Showing posts with label aldosterone. Show all posts
Sunday, February 1, 2009
Sunday, January 18, 2009
organ systems: renal system part 4- volume and pressure regulation
this is the 4th lecture in the series of the kidney and the second on the topic of osmoregulation. the last lecture basically looked at the mechanics behind osmoregulation: varying the the "motivation" (the osmotic difference between the tubules and the hypertonic interstitium) and the "permission" (the permeability of the tubules to solute and water). this section looked at the actual neuroendocrine feedback mechanisms in place which regulate fluid volume in response to changes in blood pressure or other signals. the first section introduced the importance of homeostatically maintaining the glomerular filtration rate (the rate at which blood is filtered from the glomerulus into the tubule) and renal plasma flow (the amount of blood that actually flows into the glomerulus). if the RPF and by extension GFR are too high, there is a danger that important nutrients will be simply excreted and not reabsorbed due to the fast perfusion rate through the nephritic tubules. in the reverse case, with a slow GFR / RPF, there is the danger that unwanted solutes will be reabsorbed.
GFR and RPF are thus maintained homeostatically by several different mechanisms against sharp increases or decreases in blood fluid volume and pressure. tubuloglomerular feedback is one such mechanism in which the afferent arteriole is stimulated to constrict in response to elevated blood pressure via a pathway that involves the macula densa sensing more solute particles-- causing the GFR and RPF to decrease back to normal levels. "myogenic" regulation is another, more reflexive feedback mechanism in which blood pressure changes stimulate baroreceptors in the afferent arteriole, which then constricts or dilates, depending if the blood pressure rises or falls, respectively.
we then look at the regulation of reabsorption, which occurs through multiple mechanisms. the first one mentioned is that of starling forces: the balance between hydrostatic and oncotic pressure in the capillaries. the efferent arteriole constricts and causes a pressure gradient such that while the pressure in the afferent arteriole and glomerulus is 60mmHg, the pressure in the efferent arteriole and the capillaries is 20mmHg. this pressure drop aids reabsorption in two ways: it lowers the hydrostatic pressure (less fluid coming into the capillaries), and raises the oncotic pressure (the pressure drop causes more fluid to be filtered, leaving more solutes in the plasma in the capillaries). both of these changes support reabsorption of solutes.
the next few mechanisms are all different molecules / hormones that counter blood pressure drops / increase reabsorption via different mechanisms. angiotensin II is one such molecule, and is created in response to renin release: renin cleaves angiotensin I from angiotensinogen in the kidney and liver, which is then converted to angiotensin II via angiotensin converting enzyme (ACE) in the lungs. angiotensin II has several effects on the kidney which all increase reabsorption. first, it works directly and quickly on the proximal tubules, constricting both the afferent and efferent arterioles.
second, it stimulates the release of aldosterone from the adrenal cortex, which increases the reabsorption in the distal tubules. it does so by upregulating the amount of Na/K pumps and sodium channels in the tubular membrane, thereby facilitating sodium (and thus water, which osmotically follows) reabsorption. aldosterone is also secreted in response to high potassium levels, since upregulating the Na/K pumps would increase potassium excretion.
third, it stimulates the release of ADH from the hypothalamus, which increases the collecting duct's permeability to water and thus aids reabsorption. ADH can also be released in response to blood pressure drops via the sympathetic nervous system, but generally only in response to large fluid drops such as in the case of hemorrage. (ADH is described in greater detail in lecture 3). finally, angiotensin II elicits the thirst impulse in the hypothalamus, causing an increase of fluid volume.
the next mechanism for increasing reabsorption is via the sympathetic nervous system. this pathway starts at the baroreceptors in the aortic and carotid arch, which can sense a drop in blood volume/pressure, stimulating the hypothalamus, which then triggers sympathetic activity from the medulla and spinal cord, which ultimately stimulate constriction of the afferent and efferent arteriole (recall that this increases reabsorption as in the case of angiotensin II above). this pathway can also be triggered by emotional cues such as fright and can produce a response within seconds, whereas the renin/angiotensin response is more on the order of minutes.
we then look at the factors that have the opposite effect: increasing excretion and decreasing reabsorption, generally in response to an increase in fluid volume (ingesting large amounts of liquid), increased Na+ concentration (which causes increased retention of fluid) or increased blood pressure. the first mechanism is via the atrial natriuretic peptide, which is released from the granules of the atrial baroreceptor cells in response to elevated blood pressure. in the kidney, ANP dilates the afferent arteriole, increasing GFR, and also inhibits the release of the molecules mentioned above: angiotensin II, ADH, and aldosterone. "pressure natriuresis" is the other mechanism by which excretion can be increased, and is the process in which increased blood pressure causes increased excretion of solute and water. this is accomplished via two mechanisms: first, the sodium channels and Na/K pumps are downregulated and endocytos-ed in the proximal tubule, decreasing its ability to reabsorb. second, nitric oxide is released from the endothelium of the vasa recta, which causes it to vasodilate- this increases the hydrostatic pressure and decreases the oncotic pressure, which via starling forces decreases the capillaries' absorptive capacity.
questions
1. volume of blood and extracellular fluid is regulated by...
2. sodium reabsorption is regulated by...
3. describe what happens when the GFR deviates too low or high from the homeostatic condition.
4. what regulates RBF (renal blood flow) and GFR?
5. what is the usual problem regarding regulation of renal filtration?
6. describe the tubuloglomerular feedback mechanism when body fluid volume is increased.
7. what does the macula densa release that constricts the afferent arteriole?
8. describe the myogenic mechanism for regulating renal blood flow.
9. what is the pressure drop between the afferent arterioles and the vasa recta and what is it caused by?
10. why is the pressure drop necessary?
11. what is the filtration fraction and how is it derived?
12. what are the two conditions in the capillaries necessary for reabsorption?
13. describe how the efferent arteriole influences reabsorption.
14. what is glomerulotubular balance?
15. where is fine regulation of Na+ levels and extracellular volume is carried out by?
16. what are the neuroendocrine factors that increase reabsorption and decrease excretion?
17. where and in response to what is renin released in the nephron?
18. describe the production of angiotensin II.
19. what does angiotensin II do in the kidneys?
20. describe the actions of angiotensin II on the proximal tubules of the nephron.
21. describe the actions of angiotensin II on the distal tubules of the nephron.
22. how does Captopril work?
23. describe the effect of aldosterone on the the distal tubules.
24. aldosterone is a ... secreted by the ...
25. aldosterone is released in response to...
26. sympathetic reflexes are triggered by...
27. describe how baroreceptor stimulation can lead to sympathetic stimulation of arteriole and tubular cells.
28. describe how sympathetic activity facilitates reabsorption.
29. describe the response time of sympathetic stimulation vs. that of the neuroendocrine stimulation.
30. describe ADH's role in blood volume/pressure regulation.
31. what are the two factors that decrease reabsorption / increase excretion?
32. where is atrial natruretic peptide released from?
33. how does ANP increase excretion?
34. what is pressure natriuresis?
35. what is the mechanism that it uses?
36. what role does nitric oxide play in pressure natriuresis?
37. what is the pressure natriuresis equilibrium point?
38. what are the two factors that counterbalance each other in the vasoconstriction / vasodilation of the vasa recta?
answers
1. the amount of sodium that is excreted
2. neuroendocrine factors.
3. when GFR is too low, unwanted waste products might be reabsorbed. if GRF is too high, nutrients might be excreted.
4. changes in the resistance of the afferent arteriole.
5. renal failure, where a drop of blood pressure causes too significant a drop in the renal filtration rate.
6. increased body fluid volume increases GFR and RBF, which increases solute concentration in the tubule. macula densa senses increased solute concentration and stimulates afferent arteriole to constrict, which decreases GFR and RBF to normal levels.
7. adenosine.
8. the afferent arterioles have barorecptors that are stretched when blood pressure rises, causing them to constrict reflexively, thus lowering the RBF to a normal rate.
9. 60mmHg in the afferent arterioles and 20mmHg in the vasa recta / peritubular capillaries, caused by efferent arteriole capillaries.
10. because higher pressure is necessary for filtration (hence the higher afferent arteriole pressure) and lower pressure is necessary in the capillaries for reabsorption.
11. the filtration fraction is generally 20% and is derived from the glomerular filtration rate / renal plasma flow.
12. capillary hydrostatic pressure is low, and oncotic pressure is high.
13. when the efferent arteriole constricts, the hydrostatic pressure in the capillaries drop and the oncotic pressure (because the filtration fraction increases, leaving more solute in the capillaries) increases. both of these conditions increase reabsorption.
14. a mechanism that ensures that 2/3 of the filtrate is reabsorbed in the proximal tubule despite changes in the GFR.
15. neuroendocrine control of reabsorption in the proximal and distal tubules.
16. angiotensin II, aldosterone, ADH, sympathetic nervous system.
17. in response to blood pressure drop (sensed by baroreceptors in afferent arteriole), or decreased solute concentration sensed by macula densa, renin is released by JGA cells.
18. in the liver and kidney, renin cleaves angiotensin I from angiotensinogen. angiotensin I is converted to angiotnesin II by angiotensin coverting enzyme (ACE) mostly in lungs, but also in heart and kidney.
19. releases aldosterone and promotes reabsorption of Na and water.
20. angiotensin II has a direct, fast effect on the proximal tubules: it constricts the afferent arteriole, the efferent arteriole, and stimulates the proximal tubule to reabsorb more Na+ and water.
21. angiotensin II has a slower more indirect effect on the distal tubules: it stimulates release of aldosterone from adrenal cortex, which increases Na+ and water reabsorption in distal tubules. it also stimulates the hypothalamus to secrete ADH as well as to provoke the thirst response, leading to fluid intake and increased blood pressure.
22. it is an angiotensin converting enzyme-inhibitor, which prevents ADH and aldosterone release, causing less reabsorption and thus lowering fluid volume and blood pressure.
23. increases Na+ reabsorption and K+ secretion. upregulates Na/K pump and Na channels in tubular membrane cells.
24. mineralocorticoid secreted by the adrenal cortex.
25. angiotensin II, high K+ levels in blood, ACTH released from anterior pituitary gland during stress response
26. emotional signals or drops in blood pressure.
27. aortic and carotid baroreceptors stimulate hypothalamus, which triggers sympathetic activity from medulla and spinal cord, activating the pre ganglionic neurons which innervate the prevertebral ganglia, and the post ganglionic neurons which innervate the tubular and arteriolar cells.
28. sympathetic activity stimulates constriction of afferent and efferent arterioles and stimulates renin release, thereby increasing reabsorption (see question 20)
29. sympathetic stimulation produces a response within seconds whereas the response of neuroendocrine stimulation occurs on the order of minutes.
30. baroreceptors can also stimulate ADH release in response to low blood pressure, which stimulates reabsorption in the collecting ducts and increases fluid volume and blood pressure.
31. atrial natriuretic peptide and pressure natriuresis.
32. released from granules in atrial baroreceptor cells.
33. increase GFR by dilating the afferent arteriole. decreases secretion of renin, ADH, and angiotensin II, inhibiting reabsorption of Na+ and water.
34. pressure natriuresis is the compensatory process in which increased blood pressure stimulates increased excretion of solute and water, thereby lowering blood pressure.
35. sodium channels and sodium / potassium pumps are downregulated and removed endocytically in proximal tubule cells, thereby decreasing reabsorption / increasing excretion.
36. nitric oxide is relased from the endothelium of the vasa recta in response to elevated blood pressures; this causes the hydrostatic pressure of the capillaries to go up and the oncotic pressure to go down, decreasing reabsorption and increasing excretion.
37. it is the point on the curve of salt excretion vs. blood pressure where the salt excretion (y axis) equals salt intake -- any deviation from this point will be eventually brought back by the homeostatic mechanisms discussed.
38. nitric oxide and angiotensin II.
GFR and RPF are thus maintained homeostatically by several different mechanisms against sharp increases or decreases in blood fluid volume and pressure. tubuloglomerular feedback is one such mechanism in which the afferent arteriole is stimulated to constrict in response to elevated blood pressure via a pathway that involves the macula densa sensing more solute particles-- causing the GFR and RPF to decrease back to normal levels. "myogenic" regulation is another, more reflexive feedback mechanism in which blood pressure changes stimulate baroreceptors in the afferent arteriole, which then constricts or dilates, depending if the blood pressure rises or falls, respectively.
we then look at the regulation of reabsorption, which occurs through multiple mechanisms. the first one mentioned is that of starling forces: the balance between hydrostatic and oncotic pressure in the capillaries. the efferent arteriole constricts and causes a pressure gradient such that while the pressure in the afferent arteriole and glomerulus is 60mmHg, the pressure in the efferent arteriole and the capillaries is 20mmHg. this pressure drop aids reabsorption in two ways: it lowers the hydrostatic pressure (less fluid coming into the capillaries), and raises the oncotic pressure (the pressure drop causes more fluid to be filtered, leaving more solutes in the plasma in the capillaries). both of these changes support reabsorption of solutes.
the next few mechanisms are all different molecules / hormones that counter blood pressure drops / increase reabsorption via different mechanisms. angiotensin II is one such molecule, and is created in response to renin release: renin cleaves angiotensin I from angiotensinogen in the kidney and liver, which is then converted to angiotensin II via angiotensin converting enzyme (ACE) in the lungs. angiotensin II has several effects on the kidney which all increase reabsorption. first, it works directly and quickly on the proximal tubules, constricting both the afferent and efferent arterioles.
second, it stimulates the release of aldosterone from the adrenal cortex, which increases the reabsorption in the distal tubules. it does so by upregulating the amount of Na/K pumps and sodium channels in the tubular membrane, thereby facilitating sodium (and thus water, which osmotically follows) reabsorption. aldosterone is also secreted in response to high potassium levels, since upregulating the Na/K pumps would increase potassium excretion.
third, it stimulates the release of ADH from the hypothalamus, which increases the collecting duct's permeability to water and thus aids reabsorption. ADH can also be released in response to blood pressure drops via the sympathetic nervous system, but generally only in response to large fluid drops such as in the case of hemorrage. (ADH is described in greater detail in lecture 3). finally, angiotensin II elicits the thirst impulse in the hypothalamus, causing an increase of fluid volume.
the next mechanism for increasing reabsorption is via the sympathetic nervous system. this pathway starts at the baroreceptors in the aortic and carotid arch, which can sense a drop in blood volume/pressure, stimulating the hypothalamus, which then triggers sympathetic activity from the medulla and spinal cord, which ultimately stimulate constriction of the afferent and efferent arteriole (recall that this increases reabsorption as in the case of angiotensin II above). this pathway can also be triggered by emotional cues such as fright and can produce a response within seconds, whereas the renin/angiotensin response is more on the order of minutes.
we then look at the factors that have the opposite effect: increasing excretion and decreasing reabsorption, generally in response to an increase in fluid volume (ingesting large amounts of liquid), increased Na+ concentration (which causes increased retention of fluid) or increased blood pressure. the first mechanism is via the atrial natriuretic peptide, which is released from the granules of the atrial baroreceptor cells in response to elevated blood pressure. in the kidney, ANP dilates the afferent arteriole, increasing GFR, and also inhibits the release of the molecules mentioned above: angiotensin II, ADH, and aldosterone. "pressure natriuresis" is the other mechanism by which excretion can be increased, and is the process in which increased blood pressure causes increased excretion of solute and water. this is accomplished via two mechanisms: first, the sodium channels and Na/K pumps are downregulated and endocytos-ed in the proximal tubule, decreasing its ability to reabsorb. second, nitric oxide is released from the endothelium of the vasa recta, which causes it to vasodilate- this increases the hydrostatic pressure and decreases the oncotic pressure, which via starling forces decreases the capillaries' absorptive capacity.
questions
1. volume of blood and extracellular fluid is regulated by...
2. sodium reabsorption is regulated by...
3. describe what happens when the GFR deviates too low or high from the homeostatic condition.
4. what regulates RBF (renal blood flow) and GFR?
5. what is the usual problem regarding regulation of renal filtration?
6. describe the tubuloglomerular feedback mechanism when body fluid volume is increased.
7. what does the macula densa release that constricts the afferent arteriole?
8. describe the myogenic mechanism for regulating renal blood flow.
9. what is the pressure drop between the afferent arterioles and the vasa recta and what is it caused by?
10. why is the pressure drop necessary?
11. what is the filtration fraction and how is it derived?
12. what are the two conditions in the capillaries necessary for reabsorption?
13. describe how the efferent arteriole influences reabsorption.
14. what is glomerulotubular balance?
15. where is fine regulation of Na+ levels and extracellular volume is carried out by?
16. what are the neuroendocrine factors that increase reabsorption and decrease excretion?
17. where and in response to what is renin released in the nephron?
18. describe the production of angiotensin II.
19. what does angiotensin II do in the kidneys?
20. describe the actions of angiotensin II on the proximal tubules of the nephron.
21. describe the actions of angiotensin II on the distal tubules of the nephron.
22. how does Captopril work?
23. describe the effect of aldosterone on the the distal tubules.
24. aldosterone is a ... secreted by the ...
25. aldosterone is released in response to...
26. sympathetic reflexes are triggered by...
27. describe how baroreceptor stimulation can lead to sympathetic stimulation of arteriole and tubular cells.
28. describe how sympathetic activity facilitates reabsorption.
29. describe the response time of sympathetic stimulation vs. that of the neuroendocrine stimulation.
30. describe ADH's role in blood volume/pressure regulation.
31. what are the two factors that decrease reabsorption / increase excretion?
32. where is atrial natruretic peptide released from?
33. how does ANP increase excretion?
34. what is pressure natriuresis?
35. what is the mechanism that it uses?
36. what role does nitric oxide play in pressure natriuresis?
37. what is the pressure natriuresis equilibrium point?
38. what are the two factors that counterbalance each other in the vasoconstriction / vasodilation of the vasa recta?
answers
1. the amount of sodium that is excreted
2. neuroendocrine factors.
3. when GFR is too low, unwanted waste products might be reabsorbed. if GRF is too high, nutrients might be excreted.
4. changes in the resistance of the afferent arteriole.
5. renal failure, where a drop of blood pressure causes too significant a drop in the renal filtration rate.
6. increased body fluid volume increases GFR and RBF, which increases solute concentration in the tubule. macula densa senses increased solute concentration and stimulates afferent arteriole to constrict, which decreases GFR and RBF to normal levels.
7. adenosine.
8. the afferent arterioles have barorecptors that are stretched when blood pressure rises, causing them to constrict reflexively, thus lowering the RBF to a normal rate.
9. 60mmHg in the afferent arterioles and 20mmHg in the vasa recta / peritubular capillaries, caused by efferent arteriole capillaries.
10. because higher pressure is necessary for filtration (hence the higher afferent arteriole pressure) and lower pressure is necessary in the capillaries for reabsorption.
11. the filtration fraction is generally 20% and is derived from the glomerular filtration rate / renal plasma flow.
12. capillary hydrostatic pressure is low, and oncotic pressure is high.
13. when the efferent arteriole constricts, the hydrostatic pressure in the capillaries drop and the oncotic pressure (because the filtration fraction increases, leaving more solute in the capillaries) increases. both of these conditions increase reabsorption.
14. a mechanism that ensures that 2/3 of the filtrate is reabsorbed in the proximal tubule despite changes in the GFR.
15. neuroendocrine control of reabsorption in the proximal and distal tubules.
16. angiotensin II, aldosterone, ADH, sympathetic nervous system.
17. in response to blood pressure drop (sensed by baroreceptors in afferent arteriole), or decreased solute concentration sensed by macula densa, renin is released by JGA cells.
18. in the liver and kidney, renin cleaves angiotensin I from angiotensinogen. angiotensin I is converted to angiotnesin II by angiotensin coverting enzyme (ACE) mostly in lungs, but also in heart and kidney.
19. releases aldosterone and promotes reabsorption of Na and water.
20. angiotensin II has a direct, fast effect on the proximal tubules: it constricts the afferent arteriole, the efferent arteriole, and stimulates the proximal tubule to reabsorb more Na+ and water.
21. angiotensin II has a slower more indirect effect on the distal tubules: it stimulates release of aldosterone from adrenal cortex, which increases Na+ and water reabsorption in distal tubules. it also stimulates the hypothalamus to secrete ADH as well as to provoke the thirst response, leading to fluid intake and increased blood pressure.
22. it is an angiotensin converting enzyme-inhibitor, which prevents ADH and aldosterone release, causing less reabsorption and thus lowering fluid volume and blood pressure.
23. increases Na+ reabsorption and K+ secretion. upregulates Na/K pump and Na channels in tubular membrane cells.
24. mineralocorticoid secreted by the adrenal cortex.
25. angiotensin II, high K+ levels in blood, ACTH released from anterior pituitary gland during stress response
26. emotional signals or drops in blood pressure.
27. aortic and carotid baroreceptors stimulate hypothalamus, which triggers sympathetic activity from medulla and spinal cord, activating the pre ganglionic neurons which innervate the prevertebral ganglia, and the post ganglionic neurons which innervate the tubular and arteriolar cells.
28. sympathetic activity stimulates constriction of afferent and efferent arterioles and stimulates renin release, thereby increasing reabsorption (see question 20)
29. sympathetic stimulation produces a response within seconds whereas the response of neuroendocrine stimulation occurs on the order of minutes.
30. baroreceptors can also stimulate ADH release in response to low blood pressure, which stimulates reabsorption in the collecting ducts and increases fluid volume and blood pressure.
31. atrial natriuretic peptide and pressure natriuresis.
32. released from granules in atrial baroreceptor cells.
33. increase GFR by dilating the afferent arteriole. decreases secretion of renin, ADH, and angiotensin II, inhibiting reabsorption of Na+ and water.
34. pressure natriuresis is the compensatory process in which increased blood pressure stimulates increased excretion of solute and water, thereby lowering blood pressure.
35. sodium channels and sodium / potassium pumps are downregulated and removed endocytically in proximal tubule cells, thereby decreasing reabsorption / increasing excretion.
36. nitric oxide is relased from the endothelium of the vasa recta in response to elevated blood pressures; this causes the hydrostatic pressure of the capillaries to go up and the oncotic pressure to go down, decreasing reabsorption and increasing excretion.
37. it is the point on the curve of salt excretion vs. blood pressure where the salt excretion (y axis) equals salt intake -- any deviation from this point will be eventually brought back by the homeostatic mechanisms discussed.
38. nitric oxide and angiotensin II.
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