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RACP Written 2018 > Renal - Physiology > Flashcards

Renal - Physiology Flashcards

1
Q

What are the three ways the GFR autoregulates?

A

1) autonomic vasoreactive (myogenic) reflex in afferent arteriole

2) tubuloglomerular feedback:
- reflex vasoconstriction or dilation of AFFERENT arteriole
- mediated by macula densa in thick ascending loop of henle:
Increased GFR –> increased solute delivery to macula densa–> vasoconstriction of afferent arteriole –> decreased GFR

3) angiotensin II mediated vasoconstriction of efferent arteriole

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2
Q

Increased GFR results in increased solutes delivered to what?

(In the tubuloglomerular feedback mechanism)

A

To the macula densa

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3
Q

In the tubuloglomerular feedback model, when increased solutes are delivered to the MACULA DENSA what happens?

A

Vasoconstriction of the AFFERENT arteriole

–> decreased GFR

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4
Q

In autoregulation of GFR angiotensin II does what?

A

Angiotensin II mediated VASOCONSTRICTION of EFFERENT arteriole

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5
Q

When there is decreased GFR how does that increase angiotensin II

A

Decreased GFR results in Renin produced by granular cells in afferent arteriole at Juxtaglomerular apparatus

Renin then catalyses angiotensinogen to angiotensin I

Angiotensin I is converted to angiotensin II by ACE

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6
Q

Where is renin produced and in response to what?

A

Renin is produced by granular cells in AFFERENT arteriole in juxtaglomerular apparatus

In response to decreased Renal blood flow

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7
Q

What does renin do?

A

Catalyses conversion of angiotensinogen to angiotensin I

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8
Q

In the PROXIMAL TUBULE is NaCl reabsorbed?

A

60% of NaCl resorption is in PROXIMAL TUBULE

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9
Q

In PROXIMAL TUBULE

Where is water resabsorped?

A

Through tight junctions driven by oncotic pressures and hydrostatic pressure

Also ACTIVE CHANNELS aquaporin-1

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10
Q

In the PROXIMAL TUBULE

How is Na absorbed?

A

Basolateral 3Na/2K-ATPase keeps a gradient

On APICAL SIDE:
Na-H+ exchanger
Symporter with phosphate
Symporter with glucose
Symporter with amino acids
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11
Q

In the PROXIMAL TUBULE

How is Cl absorbed?

A

Early in the tubule it isn’t absorbed

Because when Cl is left in the lumen it then enables removal of HCO3- from the lumen early on (pushing it to be converted to H20 and CO2)

But later:
APICAL side:
Cl/formate exchanger

BASOLATERAL:
K/Cl symporter

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12
Q

In the PROXIMAL TUBULE what happens to the Formate that gets secreted in exchange for Cl absorption?

A

Formate binds to H+ and forms formic acid which is reabsorbed by passive diffusion

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13
Q

In the PROXIMAL TUBULE:

How is bicarbonate reabsorbed?

A

H+ is in the lumen from Secretion by the H+/Na+ exchanger

HCO3- then binds to H+to form carbonic acid H2CO3

Carbonic acid in the lumen is converted by CARBONIC ANHYDRASE to H20 and CO2. The CO2 then diffuses passively into the cell.

Inside the cell CARBONIC ANHYDRASE reforms H2CO3 which dissociates to H+ and HCO3-.

HCO3- then exits via APICAL Na/HCO3- symporter

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14
Q

Once Bicarbonate is absorbed into the cell in the PROXIMAL TUBULE how does it exit the cell?

A

Via the Na/HCO3- symporter

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15
Q

Where does acetazolamide act?

A

Inhibits carbonic ANHYDRASE at the proximal tubule

Therefore blocks bicarbonate reabsorption

Therefore acetazolamide alkanylises the urine

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16
Q

In the PROXIMAL TUBULE what happens to ammonia?

A

Secretion

glutamine breaks down to form NH3 which diffuses out of the cell and in the lumen combines with H+ to become NH4+

In the cell some NH3 combines with H+ to become NH4+ which gets EXCHANGED with Na to be secreted into the lumen

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17
Q

What is the effect of a high K+ on ammonia in the PROXIMAL TUBULE

A

Because in the cell there is high K+ there is reduced NH+ creations (high intracellular K+ such as in HYPERALDOSTERONISM reduces ammoniogenesis)

That is why hyperaldosteronism creates Renal Tubular Acidosis Type IV

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18
Q

In the PROXIMAL TUBULE what happens to phosphate?

A

Filtered phosphate ion (PO4-) in the lumen combines with H+ (secreted by Na/H+ exchanger) to form H2PO4

Phosphate also cotransports with with Na (and this cotransporter is regulated by PTH

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19
Q

How is glucose reabsorbed?

A

In the PROXIMAL TUBULE

Apical side has SGLT2 cotransporter that moves glucose with Na from lumen into the cell

Basal side has GLUT2 transporter to exit glucose from the cell into the blood

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20
Q

How are amino acids reabsorbed?

A

In the PROXIMAL TUBULE there are Multiple apical transporters specific for different amino groups, usually cotransporters with Na+

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21
Q

What happens if peptide hormones get filtered?

A

In the PROXIMAL TUBULE

Peptide hormones (ie insulin, growth hormone, beta2 microglobulin and albumin) absorbed by absorptive endocytosis then degraded by acidified endocytic lesions.

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22
Q

What happens to protein bound drugs not filtered but that need to be renally cleared?

A

In the PROXIMAL TUBULE protein bound drugs not filtered at glomerulus (ie penecillin / cephalosporins / salicylates / oseltamivir) are SECRETED

Probenecid inhibits this secretion so raises drug plasma concentration

23
Q

How does Probenacid lower urate levels?

A

In the PROXIMAL TUBULE the organic anion transporter (OAT) reabsorbs uric acid from the lumen

If probenecid (an organic acid) is present, the OAT binds preferentially to it (instead of to uric acid), preventing reabsorption of the uric acid.

Lumen then retains more uric acid, lowering uric acid concentration in the plasma

24
Q

Why does trimethoprim raise Cr?

A

In the PROXIMAL TUBULE there is cation secretion of organic cations including Creatinine, and amine neurotransmitters such as ACh, dopamine, adrenaline and noradrenaline

trimethoprim competes with these cation transporters and raise Cr levels but don’t impair GFR

25
Q

In the PROXIMAL TUBULE which drugs are secreted by the ATP dependent p glycoprotein?

A

cyclopsorin
digoxin
Tacrolimus

26
Q

What is the only thing that happens in the thin descending loop of henle?

A

highly water permeable via aquaporin-1

27
Q

In the THICK ascending LOH how much NaCl is absorbed?

A

15-20% of NaCl

28
Q

In the THICK ascending LOH how is Na absorbed?

A

via Apical Na/K/2Cl transporter

(This is where LOOP DIURETICS ACT)

  • K+ is rate limiting substrate, but K+ also gets recycled via K+ channel
  • Also can use NH4+ instead of K+

The Gradient for Na+ created by basolateral 3Na/2K exchange

29
Q

In the THICK limb of LOH what happens to Mg?

A

Reabsorption via interstitial pathway driven by K+ recycling creating positive charge in lumen relative to interstitium

30
Q

In the THICK ascending LOH what happens to calcium?

A

Calcium resorption via interstitial pathway driven by K+ recycling creating positive charge in lumen relative to interstitium

But also calcium-sensing G protein coupled receptor CaSR regulates the NaCl reabsorption (senses high calcium levels and inhibits reabsorption by stopping the recycling of K+)

31
Q

How much of NaCl is reabsorbed in distal convoluted tubule?

A

5% of NaCl

32
Q

How is water reabsorbed in DCT?

A

It isn’t. Impermeable to water

33
Q

In the DCT how is sodium reabsorbed?

A

Absorbed on apical side by Na/Cl cotransporter

Encoded by NKCC1

(thiazide sensitive**)

Down gradient created by 3Na/2K-ATPase on basal membrane

34
Q

In the DCT how is magnesium absorbed?

A

Reabsorption via channels (genes TRPM6 + TRPM7)

**tacrolimus inhibits TRPM

35
Q

In the DCT how is calcium absorbed?

A

Apical Ca channels (TRPV5)

Basal 3Na+/Ca++ exchange

36
Q

Which diuretics act in the DCT?

A

The thiazides, and thiazide-like diuretics (ie indapamide and metolazone)

They inhibit the apical Na/Cl transporter

Because of this they also increase the Ca reabsorption (because of more positive charge in lumen)
This results in hypocaciuria and so decreases calcium renal stones

37
Q

In the collecting duct where are the principle cells located?

A

Cortical

38
Q

How much NaCl is absorbed in the collecting duct and by which cell?

A

Cortical located Principal cells absorb 5% of NaCl

39
Q

In the Cortical Duct Principal Cell how is Na absorbed?

A

Apical entry via amiloride-sensitive channels driven by gradient from basolateral 3Na/2K channels

The apical channels are called epithelial Na channels (ENaC)

Increased ENaC with aldosterone

40
Q

In the collecting duct PRINCIPAL CELLS what happens to K+?

A

SECRETION!!

K+ secreted by apical K+ channel driven by K+ gradient from 3Na/2K-ATPase exchanger on basal surface

Also driven by negative energy of the lumen once Na been reabsorption

41
Q

In the cortical collecting duct PRINCIPAL cells what would cause a DECREASES K+ secretion:

A

1) if fast tubular flow (ie volume expansion)
2) luminal nonreabsorbed anions (ie bicarb or penicillin)
3) decreased ENaC (ie trimethoprim / pentamidine)

42
Q

Where does amiloride act?

A

Amiloride blocks sodium resorption by the ENaC channels on Principal Cells of Collecting Duct

43
Q

How does lithium get reabsorbed?

A

Also comes through the ENaC channels in the cortical collecting duct Principal Cells

44
Q

Will amiloride increase or decrease serum lithium levels?

A

Decrease because it blocks ENaC channels so lithium isn’t reabsorbed

45
Q

What does BNP do in the cortical collecting duct?

A

In the principle Cells BNP binds to the basolateral surface and results in DECREASED ENaC activity, so results in less Na absorption

46
Q

What happens in Type A Intercalated Cells of Collecting Duct?

A

acid secretion and bicarb reabsorption

On the APICAL side:
H+ gets SECRETED by a H+ pump
(** this is increased with aldosterone)

H+ also gets secreted in a H+/K+ exchanger

On the BASOLATERAL side:
Bicarbonate absorbs into blood via Cl/HCO3 exchanger

47
Q

What happens in Type B Intercalated Cells of Collecting Duct?

A

bicarb secretion and acid reabsorption

  • Type B: has the proton pump on basolateral side and exchanger on apical side
48
Q

What electrolytes are reabsorbed in MEDULLARY collecting duct?

A

Na and K via Na channels and K channels in the apical membrane

Basolateral 3Na/2K exchanger channels drive the Na gradient

49
Q

Where is urea reabsorbed?

A

Medullary collecting duct

50
Q

What does aldosterone do in the kidney?

A

In the cortical medullary cell it INCREASES apical ENaC sodium absorption

In the cortical Type A intercalated Cells it INCREASES apical H+ secretion

51
Q

What does atrial natriuretic peptide and renal natriuretic peptide (urodilatin) do?

A

Inhibits the apical Na channels in medullary collecting duct

52
Q

How does Vasopresson (ADH) act in the Collecting Duct?

A

In the collecting duct on the BASOLATERAL membrane there are V2 receptors.

ADH binds to V2 receptors and results in insertion of Aquaporin 2 (AQP2) channels on the apical side to allow water into the cell

Water then exits the cell on the basolateral side via Aquaporin channels 3 and 4 (AQP3 and AQP4)

53
Q

Where does ADH bind?

A

V2 receptors on he basolateral surface of Collecting Duct Cells

RACP Written 2018 (167 decks)

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