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OS Renal > Renal Physiology II - Wall > Flashcards

Renal Physiology II - Wall Flashcards

1
Q

Normal GFR is about what?

A

120 mL/min

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2
Q

Normal RPF is about what?

A

600 mL/min

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3
Q

What is the filtration fraction?

A

Fraction of RPF that becomes GFR; normally about 20%

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4
Q

What is renal clearance formula?

A

C = (UV)/P where V=UFR

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5
Q

What are some ways the autoregulatory response can be disturbed?

A

ATII inhibition (ACE inhibitors)
NSAIDs that prevent vasodilatory prostaglandins
Inc CO2 leading to inc RPF and perfusion pressure

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6
Q

What does the kidney do during volume expansion?

A

Decrease in FF, shut off renin and AT II production, augmenting delivery to distal nephron

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7
Q

Where are Na/K ATPases found?

A

Basolateral side; never luminal side

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8
Q

Describe the capacity and resistance of the proximal convoluted tubule

A

High capacity and low resistance

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9
Q

Describe the capacity and resistance of the distal tubule

A

Low capacity and high resistance; built NOT for bulk reabsorption but maintenance of gradients

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10
Q

Which substances are reabsorbed via coupled symport?

A

Cl-, glucose, AA, lactate…phosphate

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11
Q

Where are aquaporins expressed in the tubule?

A

Proximal tubule and thin descending limb

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12
Q

What is the major difference between carriers and channels?

A

Channels are not saturable; carriers are

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13
Q

What protein makes up tight junctions?

A

Claudins

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14
Q

What is the biggest energy expenditure in the kidney?

A

Maintaining the Na/K ATPase

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15
Q

What mechanisms does the kidney have to save energy since it has to use so much ATP for the ATPase?

A

Couple transport to sodium

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16
Q

Where does the proximal convoluted tubule reside in the kidney?

A

Entirely in cortex

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17
Q

What is filtered load formula?

A

GFR x plasma concentration

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18
Q

What is reabsorbed in the proximal tubule up to the macula densa?

A

~50% of NaCL and H20
~90% of NaHCO3
100% of nutrients like glucose & AAs

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19
Q

Where are many drugs secreted into the nephron?

A

Proximal tubule

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20
Q

What is glomerulotubular balance (GTB)?

A

Matching how much of the solute is reabsorbed with how much is filtered

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21
Q

When the GFR increases, how does the proximal tubule compensate?

A

Reabsorbs higher amount of filtrate but same PERCENTAGE

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22
Q

What is the transport maximum

A

The maximum amount of a substance that can be reabsorbed or secreted

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23
Q

In which parts of the tubule is the Na-K ATPase found?

A

All parts; it is responsible for maintaining the negative cell interior and creating a sodium concentration gradient (electro and chemical gradient)

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24
Q

What happens to glucose filtration/excretion/reabsorption in the kidneys in diabetes?

A

Reabsorb glucose until the Na/glu transporter is saturated (Tm = maxed out reabsorption); if blood glucose goes up more, then it will start to be excreted into the urine and disrupts
tubule function along the way

threshold= glucose starts to be excreted

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25
Q

Describe how bicarbonate is reabsorbed in the proximal tubule

A

1) Na+/H+ antiporter spits out H+ which combines with bicarbonate
2) CA in microvilli converts into CO2 and H2O which moves through AQ-1 into cell
3) IC Ca converts them back to HCO3- and H+, which recycles
4) HCO3- leaves cell on basolateral side through specific Na/HCO3 cotransporter, which is electrogenic (3HCO3 out, 1Na+ in) and makes - charge on interstitium

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26
Q

What drives reabsorption of cations like Ca++ and Mg2+ in the proximal tubule?

A

HCO3-out/1Na+ in creates negative interstitium which attracts cations

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27
Q

What drug inhibits CA?

A

acetazolamide

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28
Q

Acetazolamide MOA

A

CA inhibitor that inhibits NaHCO3 reabsorption leading to inc excretion of NaHCO3 and water

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29
Q

What is reabsorbed in the thin descending limb?

A

Water and urea which follows it, and NO Na because no Na channels

30
Q

What is reabsorbed in the thin ascending limb?

A

Na+ reabsorbed passively, impermeable to water

31
Q

What is significant about the hairpin turn?

A

After the turn, the nephron is water impermeable (and also urea)

32
Q

Is sodium reabsorbed in the thick ascending limb?

A

Yes

33
Q

Is water reabsorbed in the thick ascending limb?

A

No

34
Q

What is the purpose of reabsorbing Na in the thick ascending limb and how is it done?

A

Active transport; critical for maintaining hypertonic medulla needed to concentrate urine

35
Q

What is the unique transporter in the thick ascending limb and what does it need to function?

A

Na/K/2Cl - needs all of that to work

on luminal side

36
Q

Explain potassium recycling in the thick ascending limb

A

Need Na/K/2Cl transporter to reabsorb ions but K is in low concentration at this point, so the cell has a potassium channel that leaks K out in order for it to come back in with Na and Cl

K recycling also gives lumen a positive charge which promotes paracellular Na,Ca,Mg reabsorption

37
Q

Explain the fate of the ions in the Na/K/2Cl transporter in the thick ascending limb

A

K is recycled; Na is pumped out into interstitium by ATPase; Cl exits cell via Cl channels

38
Q

Furosemide MOA

A

Loop diuretic that blocks Na/K/2CL transporter in thick ascending limb

By inhibiting this transporter it also inhibits Na,Ca,Mg paracellular reabsorption resulting in urinary excretion

39
Q

What is Bartter’s syndrome?

A

Mutation in Na/K/2Cl- transporter in thick ascending limb that causes diuretic effect similar to furosemide

40
Q

What is found at the end of the cortical thick ascending limb?

A

Macula densa

41
Q

How does the macula densa sense solute delivery?

A

[Cl-]

42
Q

What does the macula densa do when it senses too much delivery?

A

Constrict afferent vessel

43
Q

If renal perfusion pressure drops, how does the macula densa balance with the autoregulatory response?

A

MD causes vasodilation of afferent arteriole to increase GFR which was being maintained by autoregulatory response

44
Q

How can the afferent arteriole directly influence low flow?

A

Renin secretion

45
Q

Where is the distal convoluted tubule located?

A

Entirely in renal cortex

46
Q

What happens in the distal convoluted tubule?

A

Some NaCl reabsorption; no H20 or water resorbed; MAJOR Ca ReabsorptioN!

47
Q

What does PTH in the nephron?

A

Acts at distal convoluted tubule on the Ca2+-dependent protein on apical side to promote Ca2+ reabsorption

48
Q

What is the unique transporter in the distal convoluted tubule?

A

Electroneutral Na+/Cl- cotransporter on luminal side

49
Q

Are loop diuretics or thiazide diuretics more potent and why?

A

Loop diuretics; thiazide diuretics act at the DCT where minimal NaCl is absorbed, whereas loop diuretics act on the Na/K/2Cl- transporter in the loop where about 25% of sodium is reabsorbed

50
Q

What do thiazide diuretics do to calcium levels?

A

Decrease Ca excretion because Ca/Na transporter on basolateral side is more active at pumping in sodium when the Na/Cl transporter (which imports Na) is inhibited

51
Q

What is Gittleman’s syndrome?

A

Mutation in Na/Cl cotransporter in distal convoluted tubule

52
Q

Which diuretic would be best for someone with calcium-based kidney stones?

A

Thiazide diuretics which actually promote calcium reabsorption

53
Q

What are the two types of cells in the collecting duct and what are their functions

A

Principal cells - NaCl & H20 reabsorption, K secretion

Intercalated cells - acid-base maintenance

54
Q

Where in the nephron does aldosterone have its action?

A

Collecting duct, where it conserves salt and stimulate K secretion

55
Q

What do alpha intercalated cells do?

A

Secrete H+ via ATPase

56
Q

What do beta intercalated cells do?

A

Secrete HCO3- via Cl/HCO3 exchanger

57
Q

Where is potassium homeostasis primarily controlled?

A

Collecting duct

58
Q

Which part of the nephron is responsible for calcium regulation?

A

Distal convoluted tubule

59
Q

Explain Na and K movement in the collecting duct

A

Dilute tubular fluid doesn’t have much Na, but gradient still exists because of negative cell interior thanks to ATPase. So Na moves through CHANNEL into cell.

As a result, the fluid is now more negative, promoting K+ secretion.

60
Q

What does aldosterone do in the collecting duct?

A

Binds mineralocorticoid receptor to activate transcription of Na/K ATPase on basolateral and Na & K channels in luminal side

So, it augments sodium reabsorption and potassium secretion in the collecting duct

61
Q

How does the kidney conserve Na+ in low salt diets?

A

To conserve Na, aldosterone is released to act on CT; but it also enhances proximal reabsorption of Na so less gets to distal nephron. Less negative charge generated from Na reabsorption there, meaning drive for K secretion is lower.

62
Q

Explain the effect of high salt diet on the kidney

A

Aldosterone inactive due to volume expansion; less Na is reabsorbed due to less lumen negativity in CD. So fewer K+ channels are in the apical membrane in order to keep it from being wasted.

63
Q

In general, which diuretics will cause potassium wasting and sodium balance?

A

Those that act before the collecting duct, because they cause more Na+ to reach the CD resulting in more potential for K to leave

Loops
Thiazides
Osmotics
CA inhibitors

They lead to negative sodium balance which causes aldosterone activation and thus enhanced sodium reabsorption; then the more negative lumen keeps more K+

64
Q

Which diuretics do not cause potassium wasting and why?

A

Any diuretic that acts at the collecting duct because it does not cause increased Na reabsorption. Lead to decreased K secretion

Spironolactone
Amiloride
Triamterene

65
Q

How can the collecting duct conserve water?

A

AQP2 is waiting around in the cytoplasm and is vasopressin sensitive; when plasma osmolality due to water restriction goes up, vasopressin/ADH is released which binds basolateral V2 receptor. A GPCR/cAMP cascade inserts AQP2 into luminal membrane

66
Q

Which aquaporins are constitutively expressed in the CT and where/why?

A

3 and 4, in the basolateral membrane to return reabsorbed water into circulation

67
Q

How does the CD tubular fluid compare to the renal cortex interstitium in terms of osmolarity?

A

Tubular fluid much more dilute

68
Q

Is most water reabsorbed in the cortical or medullary collecting duct?

A

Cortical

69
Q

What does vasopressin do to alter urea movement in the nephron?

A

ADH inserts urea channels in inner medullary CD in order to pack more urea into interstitial fluid; water is conserved because it follows urea.

Water is reabsorbed from CD until the osmolarity of the tubular fluid equals the interstitium

70
Q

Name the major sites of Na reabsorption and the approximate amount reabsorbed there.

A

Proximal tubule ~50%
Loop of Henle ~40%
Distal tubule ~8%
Collecting tubule ~2%

OS Renal (25 decks)

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