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I've got kidney disease > Lecture 19 > Flashcards

Lecture 19 Flashcards

1
Q

What is the risk associated with high Na+ in the diet?

A

This can lead to high blood pressure which can lead to cardiovascular disease

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2
Q

What is normal blood pressure?
What is high blood pressure?
What is low pressure?

A

120/80 mmHg
180/110 mmHg
90/50 mmHg

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3
Q

What is the daily source of Na+? How much is this?

A

This comes from dietary intake

100 to 300 mmol/day

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4
Q

What are the daily losses of Na+?

How much are each of these?

A

sweat: 20 to 50 mmol/day
shit: 5 to 10 mmol/day
urine: few to 500mmol/day

vomit, diarrhoea, menstruation

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5
Q

What is the normal ECF and ICF concentrations of Na+?

A

ECF: 150 mM
ICF: 10 mM

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6
Q

Daily Na+ gain equals what? What does this means in terms of the net loss and gain?
What maintains this homeostasis?

A

Daily Na+ gain = daily Na+ loss
net loss and gain = 0
the nephrons maintain this

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7
Q

What is the daily filtered load of Na+?

A

filtered load = GFR x [Na+]plasma
180 L/day x 150mmol/L
27,000 mmol Na+/day

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8
Q

Which parts of the nephron are permeable to Na+?

A
  • Proximal tubule (both the convolutes and straight)
  • thin and thick ascending loop of Henle
  • distal tubule (early and late)
  • collecting duct
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9
Q

Which parts of the nephrons are impermeable to Na+?

A

the thin descending loop of Henle

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10
Q

Which of the following statements is TRUE?
A. The extracelular fluid Na+ concentration is 170
mM.
B. Normal blood pressure is 150/90 mm of Hg.
C. If you have a high NaCl diet you will excrete more
Na+ than normal.
D. All segments of the Nephron can reabsorb Na+.

A

C. If you have a high NaCl diet you will excrete more

Na+ than normal.

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11
Q

How do the nephrons handle the filtered load of Na+?

A

they due this through transporters in the apical and basolateral membrane

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12
Q

How much of the 27,000 mmol of Na+ than enter the proximal tubule is reabsorbed here?

A

18,000 mmol

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13
Q

After some Na+ is reabsorbed in the proximal tubule, how much enters the thin and thick ascending loop of Henle?

A

9000 mmol

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14
Q

How much of the 9000 mmol of Na+ that enters the thin and thick ascending loop of Henle is reabsorbed?

A

7000 mmol

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15
Q

After some Na+ is reabsorbed in the proximal tubule and thin and thick ascending loop of Henle, how much enters the distal tubule?

A

2000 mmol

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16
Q

How much of the 2000 mmol of Na+ that enters the distal tubule is reabsorbed here (total early and late)?

A

1200 mmol

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17
Q

After some Na+ is reabsorbed in the proximal tubule, thin and thick ascending loop of Henle and the distal tubule, how much enters the convoluted tubule?

A

800 mmol

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18
Q

How much of the 800 mmol of Na+ that enters the convoluted tubule is reabsorbed here? How much is excreted (not reabsorbed)?

A

600 mmol reabsorbed

200 mmol reabsorbed

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19
Q

What percentage of the filtered load of Na+ is reabsorbed in the proximal tubule?

A

67%

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20
Q

What percentage of the filtered load of Na+ is reabsorbed in the thin and thick ascending loop of Henle?

A

25%

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21
Q

What percentage of the filtered load of Na+ is reabsorbed in the distal tubule?

A

5%

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22
Q

What percentage of the filtered load of Na+ is reabsorbed in the convoluted tubule?

A

3%

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23
Q

What percentage of the filtered load is excreted?

A

1%

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24
Q

Which part of the nephron is known as the powerhouse?

A

proximal tubule

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25
Q

What sort of epithelium do the proximal tubule have? What does this mean in terms of the resistance and methods of transport?

A
  • leaky absorptive epithelium

this means that they have low resistance and paracellular and transcellular transport

26
Q

What are three examples of Na+ coupled apical transporters in the leaky absorptive epithelium in the proximal tubules? These are all examples of what type of transport?

A
  • Na+/glucose cotransport
  • Na+/H+ exchangers
  • Na+/amino acid cotransporters

these are all examples of secondary active transport

27
Q

Describe how the Na+/glucose transporter works in the proximal convoluted tubule

A

SGLT2 sits in the apical membrane and uses the downhill gradient of Na+ into the cell to also bring glucose into the cell. Glucose crosses the basolateral membrane via the GLUT2 transporter. Na+ is exchanged for K+ at the basolateral membrane by Na+/K+ ATPase. K+ is now in the cell but it leaves the basolateral membrane via a K+ channel

28
Q

How many subunits do both SGLT1 and SGLT2 have?

A

4

29
Q

Describe SGLT2

  • where is it?
  • what does it do?
  • affinity and capacity?
  • ratio of Na+ to glucose? What does this mean?
  • inhibited by what?
A
  • in the proximal convoluted tubule
  • bulk of the glucose reabsorption (90%)
  • low affinity for glucose, high capacity
  • 1:1 Na+ to glucose stoichiometry so electrogenic
  • inhibited by phloridzin
30
Q

What is the difference between affinity and capacity?

A

affinity refers to how easily glucose binds to the receptor and capacity refers to the transport rates

31
Q

Describe SGLT1

  • where is it?
  • what does it do?
  • affinity and capacity?
  • ratio of Na+ to glucose? What does this mean?
  • inhibited by what?
A
  • in the proximal straight tubule
  • fine tuning of the glucose reabsorption (10%)
  • high affinity for glucose in low conc, low capacity
  • 2:1 Na+ to glucose stoichiometry so electrogenic
  • inhibited by phloridzin
32
Q

Describe how the Na+/H+ exchanger works in the proximal tubule

A

NHE (such as NHE3) is in the apical membrane and exchanges one Na+ (into the cell) for one H+ (out of the cell)
The H+ comes from carbonic anhydrase converting CO2 and H2O into H+ and HCO3-.
HCO3- and Na+ leave together through the basolateral membrane via the NBC1 channel.
There is a Na+/K+ ATPase on the basolateral membrane which allows Na+ out and K+ in and then K+ exits the basolateral membrane via a leak channel

33
Q

Which isoform of the Na+/H+ exchanger NHE is the dominant apical membrane isoform?

A

NHE3

34
Q

What are the isoforms of NHE that are in the kindey?

A

NHE1, NHE2, NHE4

35
Q

What is the purpose of NHE3?

A

It moves Na+ down its concentration gradient for exchange of H+ up its concentration gradient. It is used in pH balance

36
Q

Which of the following statements is FALSE?
A. The Proximal tubule is the ‘powerhouse’ of the Nephron.
B. 100% of filtered glucose is reabsorbed by the SGLT2 and SGLT1 of the Proximal tubule cells.
C. If you have a high NaCl diet you will excrete more Na+ than a person who has a NaCl normal.
D. SGLT2 has a higher affinity for glucose than SGLT1

A

D. SGLT2 has a higher affinity for glucose than SGLT1

37
Q

What is the cotransporter in the thin and thick ascending loops of Henle?

A

Na+/K+/2Cl- cotransporter (NKCC2)

38
Q

Describe the absorption of Na+ in the thick ascending loop of Henle

A

NKCC2 brings in 2Cl- ions, an Na+ ion and a K+ ion into the cell. K+ leaves the apical membrane via the ROMK channel. Na+ is brought into the cell in exchange for H+ via the NHE3 at the apical membrane. The H+ comes from carbonic anhydrase converting CO2 and H2O into H+ and HCO3-.
Na+ is pumped out of the cell in exchange for K+ be Na+/K+ ATPase in the basolateral membrane. Cl- leaves the cell through Cl- leak channel on the basolateral membrane. It also leaves cotransported with K+ at the basolateral membrane. HCO3- is pumped out of the cell in exchange for Cl- coming into the cell by AE2 at the basolateral membrane

39
Q

How many different types of Barter syndrome are there?

A

3

40
Q

What causes the three different types of Barter syndrome?

A
  1. when the NKCC is malfunctioning which leads to the loss of Na+
  2. mutation of the ROMK K+ channel
  3. mutation of the Cl- channel in the basolateral membrane
41
Q

NKCC2 does what to Na+, Cl- and K+?

A

It moves Na+ and Cl- move down its concentration gradient and K+ against its concentration gradient

42
Q

What is NKCC2 selectively inhibited by?

A

it is selectively inhibited by “loop diuretics” bumetanide and frusemide

43
Q

How many mmol of Na+ is received by the distal tubules each day?

A

2150 mmol

44
Q

The early distal tubule has transport function similar to the what?

A

thick ascending loop of the loop of Henle

45
Q

The late distal tubule has transport function similar to what?

A

the collecting duct

46
Q

How many mmol of Na+ do the distal tubules reabsorb? What percent of the daily filtered Na+ load is this?

A

1350 mmol

5%

47
Q

Which transporters are in the distal tubule?

A
  • Na+/Cl- cotransporter (NCCT) is in the early distal tubule

- Na+ channels (ENaC) is in the late distal tubule (and collecting duct)

48
Q

Describe the absorption of Na+ in the early distal tubule

A

Na+ and Cl- are cotransported across the apical membrane into the cell via NKCC. K+ and Cl- are cotransported out of the cell via the lateral membrane. Cl- and K+ also flow out of the basolateral membrane via their respective leak channels. Na+/K+ ATPase is also working in the basolateral membrane

49
Q

NCC have what percentage similarity to NKCC1?

A

60%

50
Q

What is NCC inhibited by?

A

thiazide diuretics

51
Q

Which of the following statements is TRUE?
A. Cells of the Thin and Thick Ascending Loops of Henle
reabsorb 30% of the filtered Na+.
B. The Na+-Cl- cotransporter is the main transport protein that secretes NaCl by the Thin/Thick Ascending Limbs.
C. The Na+-K+-2Cl- cotransporter is inhibited by thiazide diuretics.
D. The cells of the Distal Tubule reabsorb 5% of the filtered Na+

A

D. The cells of the Distal Tubule reabsorb 5% of the filtered Na+

52
Q

What type of epithelium does the collecting duct have? What does this mean for the resistance and movement?

A

tight absorptive

this means that there is high resistance and transcellular movement

53
Q

What channel does the collecting duct have?

What is this blocked by?

A

apical ENaC channel blocked by amiloride

54
Q

How many subunits does ENaC have? What are these called?

A

3

and α, β, γ

55
Q

How many transmembrane domains does each subunit of ENaC have?

A

2

56
Q

What does each subunit of ENaC have?

A

a large extracellular loop

57
Q

What motif does ENaC have? Where is it? What does this consist of?
What is this important for?

A

On the carboxy terminus, there is the PY motif (PPPXY) consisting of proline (P) and tyrosine (Y)
it is important in protein-protein interactions

58
Q

What are the two types of cells does the collecting duct have?

A

principle cells for Na+ and K+ balance

intercalated cells

59
Q

What is ENaC regulated by?

A

aldosterone

60
Q

What are two molecule defects/ diseases that come from ENaC?

A

Liddle’s syndrome

Pseudohypoaldosteronism Type I

61
Q

Explain Liddle’s syndrom

A

This is a gain of function mutation due to mutations of the COOH termini of β and γ subunits. There are too man channels and therefore too much Na+ is reabsorbed.

62
Q

Explain Pseudohypoaldosteronism Type I

A

This is a loss of function due to a mutation of the NH2 terminus of the α subunit. There are too few channels and therefore not enough Na+ is reabsorbed.

I've got kidney disease (43 decks)

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