this pharm lecture focused on the conventional medications designed to control blood pressure, of which there are many. the first category is diuretic medications, controlling blood pressure by modifying the kidney's filtration functioning. thiazide diuretics such as hydrodiuril act on the thick ascending loop and early distal tubule to inhibit sodium and chloride reabsorption, thereby increasing water excretion and lowering blood pressure. they also increase calcium and uric acid levels by acting on the proximal tubule. thus, the side effect of thiazide diuretics are hypokalemia, hyponatremia, and hypercalcemia / hyperuricemia. they are commonly used in conjunction with ACE inhibitors and beta blockers.
loop diuretics such as lasix are the most potent of all the types of diuretics and work by blocking the Na/K/Cl cotransporter system in the loop of Henle. they have similar side effects to thiazide diuretics; hypokalemia, hyponatremia, etc. in terms of potency, they are stronger than thiazide diuretics and thus the preferred diuretic in renal disease or hypertensive emergencies.
potassium sparing diuretics such as aldactone inhibit sodium / chloride reabsorption but also promote potassium reabsorption and therefore are sometimes used in conjunction with potassium wasting diuretics such as loop diuretics. it is a direct antagonist to aldosterone. because of the potential for hyperkalemia these medications should be avoided in patients who are taking potassium supplements, or other medications that raise potassium levels such as ACE inhibitors or ARB's.
these diuretics all work by promoting the excretion of fluid from the kidneys, thereby reducing the body's total fluid volume and thus lowering blood pressure. another mechanism that is used to lower blood pressure is via blocking the beta-2 receptors in the heart, which ultimately lowers cardiac output and therefore lowers blood pressure. "beta blockers" such as propanolol are non-specific, meaning they will also affect the beta receptors on peripheral vasculature, causing dilation, as well as the beta receptors on bronchial smooth muscle (the same ones that asthma medications seek to stimulate), causing bronchoconstriction. thus these medications must be used cautiously with patients who have respiratory issues. even the never, "cardio-selective" atenolol which preferentially seeks the beta-2 receptors in the heart also cause non-selective effects at higher doses. all beta blockers can cause CNS depression, sexual dysfunction, and bradycardia-- if acute episodes occur, this can be treated with glucagon, which antagonizes beta blockers' effects between the SA and AV node.
another class of drugs, alpha-1 adrenergic antagonists, block the alpha-1 receptors on peripheral vasculature smooth muscle to cause dilation, which causes a decrease in total peripheral resistance, thus lowering blood pressure. BPH patients might also be benefitted by the relaxation of the bladder neck / prostate. prazosin / minipress is an example, as well as reserpine (which is derived from the alkaloids of rauwolfia).
calcium blockers work by blocking the influx of calcium into smooth muscle cells of the peripheral vasculature as well as cardiac muscle cells, promoting relaxation and dilation, thereby lowering peripheral resistance. they might also have a "negative inotropic effect", which can diminish cardiac output - thus care is needed when administering to patients with CHF or bradycardia. verapamil / isopten is one example, and is indicated for hypertension, CHF, and angina-- in particular, atypical angina due to vasospasm. calcium blockers can be sometimes be used in combination with beta blockers in order to wean a patient off of beta blockers, which have much more severe withdrawal symptoms in the form of rebound hypertension, etc.
there are a couple classes of drugs that work on the renin / angiotensin system- first is the ACE inhibitors (angiotensin converting enzyme inhibitors). as the name suggests, these drugs block the conversion of angiotensin I to angiotensin II, a hormone that facilitates water retention on a large scale in the body. they are particularly effective for diabetics with hypertension due to their actions to counteract diabetic nephropathy by reducing glomerular capillary pressure. ACE inhibitors tend to raise K+ levels, thus one must not use a potassium sparing diuretic in combination, although other diuretics seem to potentiate their actions. the other mechanism that ACE inhibitors have is to prevent the degradation of bradykinins, which leads to a common side effect of a dry cough, since bradykinins stimulate the medullary cough reflex.
other drugs that works with the renin / angiotensin system are angiotensin II receptor blockers such as losartan / cozaar. although the mechanism is different (blocking the receptors as opposed to blocking the conversion of angiotensin II, and no bradykinin involvement) the profile is similar to ACE inhibitors in that they are good for diabetic patients with hypertension, can cause hyperkalemia, and are contraindicated in pregnancy.
questions
introduction...
1. how does "hypertension beget hypertension"?
2. mechanism of thiazide diuretics?
3. indication of thiazide diuretic?
4. thiazide diuretics often used in conjunction with...
5. what occurs at the proximal tubule with thiazide diuretics?
6. thiazide side effects?
7. examples of thiazide diuretics?
8. what supplement in recommended with thiazide diuretics?
loop diuretics...
9. example of loop diuretic?
10. physiological mechanism?
11. side effects of loop diuretics?
12. loop diuretics are the preferred form of diuretics for...
13. loop diuretics can be used to treat what other condition?
14. how do loop diuretics compare in strength to other diuretics?
15. lasix should be avoided in patients with what allergy?
potassium sparing diuretics...
16. example of a PSD?
17. mechanism of action?
18. direct antagonist to...
19. avoid use with patients who are on...
beta blockers...
20. general mechanism of action?
21. if the beta blocker is non selective, what other effects might it have?
22. which beta blockers are selective and which are not?
23. disadvantages to beta blockers?
24. why is abrupt discontinuation not recommended?
25. besides hypertension / cardiac symptoms, what else is propranolol used for?
26. what can be administered to counter the effects of a beta blocker induced acute bradycardia?
alpha-1 adrenergic antagonists...
27. example of an alpha antagonist?
28. mechanism of action?
29. how can these medications additionally benefit patients with BPH?
30. what is an herb that has alpha-1 adrenergic effects?
calcium channel blockers...
31. mechanism of action?
32. what is the "negative inotropic effect"?
33. what is an example?
34. what are the specific indications for [33]?
35. side effects?
36. how do rebound effects compare for calcium vs. beta blockers?
ACE inhibitors...
37. two mechanisms for ACE inhibitors?
38. ACE inhibitors often the drug of choice in treating...
39. least likely of the anti-hypertensives to cause...
40. effect on electrolytes?
41. ACE inhibitors work well in combination with...
42. number one side effect? why?
43. other side effect?
44. pregnancy?
angiotensin II blockers...
45. how does the mechanism differ from ACE inhibitors?
46. example of an AII blocker?
direct vasodilators...
47. mechanism of action?
48. examples of direct vasodilators?
49. side effects for the first example in [48]?
50. side effects for the second example in [48]?
answers
1. prolonged hypertension results in smooth muscle hypertrophy and proliferation in arterioles, which increases total peripheral resistance, thereby raising blood pressure.
2. inhibit sodium and chloride reabsorption in the thick ascending loop and early distal tubule, thereby increasing sodium and water excretion in the urine.
3. mild hypertension with chronic edema.
4. beta blockers and ACE inhibitors.
5. holding back of calcium and uric acid.
6. decreased Na, K, Mg. increased Mg, Ca.
7. hydrochlorthiazide / hydrodiuril.
8. potassium.
9. furosemide / lasix.
10. block the Na/K/Cl cotransporter system in ascending loop of henle.
11. hyponatremia, hypokalemia, hypocalcemia, hypomagnesemia, hyperglycemia, hyperuricemia.
12. patients with renal disease and hypertensive emergencies.
13. hypocalcemia.
14. generally stronger.
15. sulfonamide allergies.
16. spironolactone / aldactone.
17. inhibits Na/Cl reabsorption while promoting potassium reabsorption.
18. aldosterone.
19. ACE inhibitors, potassium supplements, ARB's.
20. reduce beta-1 receptors in the heart, causing decreased cardiac output.
21. if it affects beta-2 receptors, peripheral vasculature will be dilated and bronchial smooth muscle will constrict.
22. propanolol is non-selective, atenolol is.
23. CNS effects, sexual dysfunction, bradycardia.
24. because of rebound tachycardia / hypertension due to upregulation of beta receptors during the period of medication.
25. stage fright and migraine headache prophylaxis.
26. glucagon-- blocks the beta blocker action between the SA and AV node.
27. prazosin / minipress
28. blockage of alpha-adrenergic sites in peripheral vasculature causes dilation.
29. relaxation of smooth muscle around bladder neck and prostate, allowing urine to pass more easily.
30. rauwolfia alkaloids have peripheral adrenergic blocking effects.
31. blockage of influx of calcium into smooth muscle cells around peripheral vasculature as well as cardiac cells causes dilation, thereby lowering peripheral resistance.
32. a side effect of calcium channel blockers-- decreased cardiac output. thus these medications might be contraindicated for patients with CHF or bradycardia.
33. verapamil / isopten
34. hypertension, angina (especially atypical), CHF
35. flushing, headache, hypotension.
36. calcium blocker rebound effects are much less.
37. 1) block conversion of angiotensin I to angiotensin II. 2) prevent degradation of bradykinins, reducing peripheral vascular resistance.
38. diabetic patients with hypertension.
39. sexual dysfunction in males.
40. tends to increase potassium levels.
41. diuretics.
42. dry irritating cough, due to bradykinin stimulation of the medullary cough reflex.
43. angioedema, especially of tongue and oropharyngeal area.
44. never-- category X.
45. block the angiotensin II receptors, and no involvement of bradykinins.
46. lozartan / cozaar.
47. opening potassium channels in vascular smooth muscle.
48. minoxidil, hydralazine.
49. hirusitism.
50. drug induced lupus syndrome.
Showing posts with label diuretics. Show all posts
Showing posts with label diuretics. Show all posts
Monday, October 4, 2010
Sunday, February 1, 2009
organ systems: blood pressure regulation, potassium, diuretics
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+.
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+.
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