Lecture 15: renal diluting systems & collecting systems

Question 1

what parts of the nephron are permeable vs imperable to water?

Answer 1

* water permeable: proximal tubule and descending loop of henle
* water impermeable: ascending thin loop of henle, thick ascending loop of henle & early part of distal tubule

Question 2

In which part of the nephron does the permeability to water depend on circulating levels of ADH?

Answer 2

the late part of the distal tubule and collecting tubule

Question 3

what** proteins** are expressed along the PCT and descending loop of henle to allow for water reabsorption?

Answer 3

APQ1 expressed on apical and basolateral membrane of both
* APQ7 also expressed on apical membrane of straight PT

Question 4

what are the names of the** constitutive aquaporins** that are present in the CD?

Answer 4

• AQP3 and AQP4 are present on the basolateral membrane of principal cells

Question 5

What is the name of the facultative (only expressed when needed) aquaporin in the CD?

Answer 5

• Facultative ACP2

Question 6

How does water move out of the tubules back into the blood (reabsorption) in the late distal tubule and collecting tubules?

Answer 6

• under hormonal control ONLY
• Antidiuretic hormone - released if you are dehydrated to reabsorb water in body and maintain it

Question 7

what is the mechanism of ADH on the collecting tubules?

describe the steps

Answer 7

• when a person is dehydrated, ADH is released
• ADH binds to the V2 receptor on the basolateral membrane of collecting duct cells
• receptor activates cAMP messanger system
  cAMP activates protein kinase A
• this leads to an increased expression of AQP2 channels (aquaporin 2 channels) that are inserted into the apical membrane
• H20 reabsorbed through these channels back into blood
• when ADH is removed, APQ2 channels are internalised into the cell and the apical membrane is impermable to h20

Question 8

Describe how the tubular fluid becomes hypotonic (in relation to the plasma) in the late distal tubule

Answer 8

• tubular fluid starts off as isosmotic
• As the PCT and loop of henle are permeable to water, water is reabsorbed here and there is a higher concentration of Nacl in tubular fluid relative to plasma
• after the think and thick ascending loops - lots of NaCl is reabsorbed and the tubular fluid contains less Nacl relative to plasma and therefore is hypo-osmotic

Question 9

Describe the process of Na+ reabsorption in the thick ascending limb of the loop of henle

Answer 9

• the basolateral Na+K+ATPase pump provides the driving force for transcellular transport in the TAL - ie maintains a low intracellular [Na+]
• movement of Na+ across the apical membrane is mediated by the** NKCC2 symporter **
• there** must be a presence of K+ channels** on the apical membrane to allow the NKCC2 to function
• movement of Na+ across the apical membrane is also mediated by Na+-H+ antiporter (Na+ in and H+ out)
• there is reabsorption of K+, Cl- and HCO3 across basolateral membrane via seperate pathways

Question 10

How much (%) of the Na+ reabsorption is paracellular?

Answer 10

50%

Question 11

why does 50% of the reabsorption of Na+ take place via paracellular route?

Answer 11

• as there is a dominance of K+ channels in the apical membrane of TAL, it results in a lumen positive voltage charge
• the positive voltage charge drives the paracellular reabsorption of several cations including Na+,K+,Mg2+ and Ca2+

Question 12

why is the TAL also called the diluting segment?

Answer 12

as the TAL is impermeable to water and does not reabsorb it, the tubular fluid is** diluted.. the osmolality of the fluid may be reduced as low as 100mOsm**

Question 13

what transporter do loop diuretics block?

Answer 13

NKCC2 co transporter is inhibited by loop diuretics

Question 14

What does the distal nephron consist of?

Answer 14

• the early distal tubule
• the late distal tubule
• the connecting tubule
• the collecting duct

Question 15

Describe the Na+ reabsorption process in the early DCT

Answer 15

• the **basolateral Na+/K+/ATPase pump **maintains a low intracellular [Na+] in the early distal convoluted tubule
• entry of Nacl across apical membrane is** mediated by NCC (Na+/Cl-) symporter**
• Cl- leaves the cell via diffusion through Cl- channels
• the early DCT is** impermeable to water** thus **dilution of tubular fluid continues ** (as more Na+ leaves)

Question 16

Describe Na+ reabsoroption in the late DCT and collecting ducts

Answer 16

*2 types of cell in the collecting tubule and late DCT - principal cells (Na+) and intercalated cells (for acid-base physiology)

Na+/K+/ATPase pump is present on the** basolateral side of the principal cell** & maintains a low [Na+]
* this sets up a gradient for Na+ to enter the cell through** ENaC channels** (epithelial Na+ channels) on the apical surface of the principal cells
* Na+ leaves the cell through Na+/K+/ATPase pump

Question 17

what hormone is the ENaC channel regulated by?

Answer 17

aldosterone