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+.
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