Control of Blood Volume

Question 1

What ion usually goes along with Na+ to maintain electroneutrality?

Answer 1

Cl-

Question 2

Why not just add/remove water to or from the plasma to change its volume?

Answer 2

Because that would change the plasma osmolarity

Question 3

Where in the nephron does the majority of sodium reabsorption occur?

Answer 3

Proximal tubule

Question 4

Describe the fluid that leaves the proximal tubule in terms of its osmolarity

Answer 4

Isosmotic - because as ions are reabsorbed, water is also reabsorbed maintaining the osmolarity of the fluid in the PCT

Question 5

Describe the permeability of the thin descending limb of the loop of henle

Answer 5

Very permeable to water, less to ions

Question 6

What is proximal tubule Na+ reabsorption stimulated by?

Answer 6

RAAS

Question 7

When renal artery BP increases, what causes reduction in sodium reabsoption in the proximal tubule?

Answer 7

Reduced number of Na-H antiporter and reduced Na-K-ATPase activity

Question 8

Where is all the glucose and amino acids reabsorbed?

Answer 8

PCT

Question 9

Where is the majority of sodium, chloride and potassium reabsorbed?

Answer 9

PCT

Question 10

What are the two routes through which reabsorption can take place?

Answer 10

Transcellular - through a cell

Paracellular - via the intercellular space between cells

Question 11

What is the main transporter in the PCT on the basolateral side of cells?

Answer 11

3Na-2K-ATPase

Question 12

What does the basolateral side of cells face?

Answer 12

Faces the interstitium

Question 13

What does the apical membrane face?

Answer 13

Lumen

Question 14

Describe what the NaKATPase does in the tubule

Answer 14

Pumps out Na+ ions using active transport

This creates an electrochemical gradient which favours the movement of Na+ into the cell from the apical side

Question 15

Where in the nephron are there NO aquaporins present?

Answer 15

Ascending limb of the loop of henle

Question 16

Where are AQP1 channels present?

Answer 16

PCT and descending loop of henle

Question 17

Where are AQP2, AQP3 and APQ4 channels present?

Answer 17

Collecting ducts

Question 18

What channels are present in the proximal tubule that involve sodium?

Answer 18

1) Na-H antiporter
2) Na-Glucose symporter
3) Na-AA co-transporter
4) Na-Pi

Question 19

What are the three regions of the proximal tubule and how are these divided?

Answer 19

S1, S2, S3

Pars convolute resides in cortex, divided into S1 and proximal part of S2

Pars recta resides in outer medulla - makes up distal part of S2 and S3

Question 20

What is the S1 segment of the proximal tubule impermeable to and what is the significance of this?

Answer 20

Not permeable to urea and Cl-

Their concentration increases in S1 which creates a concentration gradient which is used in the S2 and S3 segments.

In S2 and S3, Cl- can be transported from the lumen of the tubule into the peritubular capillaries either paracellularly or transcellularly down their concentration gradient

Question 21

How is glucose reabsorbed in the proximal tubule?

Answer 21

Transported across apical membrane against their concentration by co-transport - SGLUT transporters move glucose with 2 sodium ions. Then, glucose crosses the basolateral membrane via facilitated diffusion.

Question 22

How are amino acids reabsorbed in the proximal tubule?

Answer 22

Na+/amino acid symporters are present on the apical side of cells in the S1 segment which reabsorbs all the amino acids

Question 23

What does the Na+/H+ antiporter do in the PCT?

Answer 23

Moves Na+ ions in to the tubular cells and expels H+ into the tubule (maintains pH)

Question 24

How is sodium reabsorbed in the S1 segment of the PCT?

Answer 24

1) Na-H exchange
2) Co-transport with glucose (SGLT2)
3) Co-transport with amino acids
4) Co-transport with phosphate

Question 25

On which membrane is Na-K-ATPase located?

Answer 25

Basolateral

Question 26

On which membrane is the SGLT transporter located?

Answer 26

Apical

Question 27

Which is the primary site of sodium reabsorption in the loop of henle?

Answer 27

Thick ascending limb

Question 28

How is sodium absorbed in the thick ascending limb?

Answer 28

Via NKCC2 on the apical membrane

Question 29

How does the NKCC2 transporter work?

Answer 29

Moves one sodium ion, one potassium ion and two chloride ions across the apical membrane

Question 30

How does the sodium potassium ATPase on the basolateral membrane establish an electrochemical gradient?

Answer 30

By pumping 3 sodium ions out of the cell and 2 potassium ions into the cell - creating a low intracellular concentration of sodium and also making the inside of the cell negatively charged (meaning sodium can move down its electrochemical gradient through transporters on the apical membrane)

Question 31

In the thick ascending limb, how are potassium ions transported back into the tubule?

Answer 31

Via ROMK channels (prevents toxic build up of potassium within the cell)

Question 32

In the thick ascending limb, how are chloride ions transported out of the cell into the tissue fluid?

Answer 32

Via CIC-KB channels

Question 33

How does water reabsorption occur in the thin descending limb?

Answer 33

Passively, via AQP1 channels | No sodium reabsorption

Question 34

What is Bartter syndrome?

Answer 34

Genetic condition caused by mutations in the genes that code for the NKCC2 transporter, apical potassium channel or basolateral chloride ion channel. This results in decreased NaCl reabsorption Leads to hypokalaemia because more sodium being reabsorbed in the distal tubule leading to increased excretion of K+ Leads to hypovolaemia as decreased reabsorption of NaCl means less osmotic pressure

Question 35

What can be used to treat hypertension by inhibiting the NKCC2 transporter in the thick ascending limb?

Answer 35

Loop diuretics

Question 36

How do loop diuretics work?

Answer 36

Inhibit NKCC2 in the thick ascending limb Increase excretion of NaCl in the urine Reduces water absorption Therefore reduces plasma volume

Question 37

Describe the histology of PCT cells

Answer 37

- Brush border - Large outside diameter - Lots of mitochondria

Question 38

Where does sodium reabsorption occur in the nephron?

Answer 38

PCT, ascending loop of henle, DCT and collecting duct

Question 39

What happens when all the glucose transporters are saturated with glucose?

Answer 39

Glucose goes in the urine

Question 40

When are glucose transporters fully saturated?

Answer 40

At 11 mmol/L

Question 41

On which membrane is ROMK found in the thick ascending limb?

Answer 41

Apical membrane

Question 42

On which membrane is NKCC2 found in the thick ascending limb?

Answer 42

Apical membrane

Question 43

What drug inhibits the action of the Na-H exchanger in the PCT?

Answer 43

Amiloride

Question 44

What transporter is regulated by parathyroid hormone?

Answer 44

Sodium dependent phosphate transporter in the proximal tubule

Question 45

How is albumin reabsorbed in the proximal tubule?

Answer 45

Albumin taken in to tubular cells via receptor mediated endocytosis Then lysosome breaks it down into its amino acids and the amino acids are transported into the capillary via passive amino acid transporters

Question 46

What happens to the K+ and Cl- after they are taken into the cell with sodium via NKCC2 in the thick ascending limb?

Answer 46

K+ diffuse via ROMK back into lumen | Cl- ions move into interstitium

Question 47

In the thick ascending limb, why is it vital that K+ diffuses back into the filtrate after entering tubular cells via NKCC2?

Answer 47

In order to maintain activity of NKCC2 Otherwise there would be a lower concentration of K+ in the lumen so K+ would want to move from the tubular cells into lumen rather than the other way around

Question 48

Why is the ascending limb known as the diluting segment?

Answer 48

Because the ascending limb reabsorbs NaCl but not water Descending limb reabsorbs water but not NaCl

Question 49

Describe the osmolarity of the tubule fluid leaving the loop

Answer 49

Hypo-osmotic (more dilute) compared to plasma

Question 50

What is the role of the early DCT?

Answer 50

Absorption of ions, including Na+ , Cl- and Ca2+

Question 51

How does NaCl enter across the apical membrane in the early DCT?

Answer 51

Via electroneutral NCC transporter

Question 52

What drug acts on the NCC transporter in the DCT?

Answer 52

Thiazides

Question 53

What transporter does amiloride target?

Answer 53

ENaC in DCT

Question 54

How does NaCl enter and leave the tubular cell in the late DCT?

Answer 54

Enters via NCC and ENaC on the apical membrane | Leaves via NaKATPase on the basolateral membrane

Question 55

What diuretics is ENaC sensitive to?

Answer 55

Amiloride

Question 56

Is movement through ENaC electroneutral?

Answer 56

No, difference drives paracellular Cl- ion reuptake

Question 57

Describe the osmolarity of the fluid leaving the DCT

Answer 57

More hypo-osmotic - further dilution has occurred

Question 58

Where is a major site of calcium reabsorption?

Answer 58

DCT

Question 59

Describe calcium reabsorption in the DCT

Answer 59

There is apical calcium transport - then cytosolic calcium immediately binds to calbindin which shuttles calcium to the basolateral aspect of the DCT cell. It is then transported out via NCX

Question 60

What are the two main types of cell found in the collecting duct?

Answer 60

Principal cells and intercalated cells

Question 61

How do principal cells of the CD reabsorb sodium?

Answer 61

Via ENaC

Question 62

What do intercalated cells do?

Answer 62

Secrete either H+ or HCO3- to alter blood pH

Question 63

What does spironolactone do?

Answer 63

Acts as an antagonist of aldosterone receptor in the collecting duct - reduces sodium reuptake