Week 12: Renal Physio 2 (Ben)

Question 1

What drug can block bicarbonate/Na⁺ reabsorption in the proximal tubule?

Answer 1

Acetazolamide

• inhibits carboanhydrase

Question 2

What two mechanisms of action cause blocking of water reabsorption in the proximal tubule?

Answer 2

1. Aquaporin Inhibition - via mercury-containing compounds
2. Non-Reabsorbed Osmolites
   
   • mannitol
   • inulin
   • excessive glucose
   • ketone bodies

Question 3

What kind of transport takes place in the thin segment of the loop of Henle?

Answer 3

passive transport only

Question 4

What transport process takes place in the thin descending limb of the loop of Henle?

What is the consequence of this for the tubular fluid?

Answer 4

Water Reabsorption

• the tubular fluid osmolarity equilibrates with that of the (hyperosmotic) interstitial fluid

Question 5

What are two important differences of the thin ascending limb from the thin descending limb?

Answer 5

The thin ascending limb is…

1. Impermeable to water
2. Permeable to urea (leading to excretion into the tubule from the interstitium)

Question 6

What happens to sodium in the thick ascending limb?

How?

Answer 6

Na+ is reabsorbed in the TAL

• coupled with K+ and Cl- on the luminal side
  
  • K+ leaks back out to lumen + interstitium
  • Cl- leaks into interstitium
• Na+/K+ ATPase on interstitial side

Question 7

What common diuretic affects TAL processes and how?

Answer 7

Furosemide

• inhibits the Na+/K+/2 Cl- transporter on the luminal side of TAL cells

Question 8

What important part of TAL Na+ reabsorption can be inhibited by acidosis?

Answer 8

K⁺ channel

• on the luminal side
• stops K+ from re-entering lumen to be transported with the re-absorbed sodium

Question 9

What happens to Na+ in the DCT?

Answer 9

Na+ Reabsorption

• 5-7% occurs in DCT

Question 10

What drug class affects the DCT’s action on sodium?

How?

Answer 10

Thiazide Diuretics

• inhibit the luminal Na+/Cl- channel

Question 11

What happens to Na+ in the connecting duct and collecting duct?

Via what type of channels?

Answer 11

Na+ Reabsorption

• via ENaC

Question 12

What two hormones affect sodium transport in the connecting/collecting ducts?

How?

Answer 12

1. Aldosterone - stimulates ENaC synthesis + transport to membrane
2. ANP - inhibits ENaC function (thus inducing “natriuresis”)

Question 13

What happens to the tubular potential in the connecting/collecting ducts?

Why?

Answer 13

Tubular potential becomes negative (-20 to -50 mV)

• large amts of Na⁺ are re-absorbed, removing + charges from the tubular fluid

Question 14

Movements of what two ions are influenced by the negative connecting/collecting duct tubular potential?

How do these ions move?

Answer 14

Chloride - reabsorbed paracellularly via tight junctions

Potassium - excreted into the lumen via K⁺ channels

Question 15

What drug effects ion reabsorption in the connecting/collecting ducts and how?

Answer 15

Amiloride

• inhibits ENaC channel
• Na+ stays in lumen, keeping water with it, thus this is a K+-sparing diuretic

Question 16

How does water reabsorption occur in the connecting/collecting ducts?

(Where there is no constitutive expression of aquaporins on the luminal membrane.)

Answer 16

1. ADH/Vasopressin binds to V2 receptor on interstitial side of cell
2. Intracellular cAMP increase activates PKA, leading to…
3. Release of Aquaporin 2 from vesicles + their movement to luminal membrane

Question 17

How is urea reabsorption regulated in the inner medullary collecting duct?

Answer 17

1. ADH/Vasopressin binds to V2 receptor on interstitial side of cell
2. cAMP —> PKA —> Phosphorylation
3. UT-A1 urea transporters release from vesicles and are expressed on luminal membrane

Question 18

How is K+ handled in the proximal tubule?

What is the driving force?

Answer 18

• Paracellular reabsorption
• Coupled with Na+
• Driving Force: electric gradient
  
  • via Cl^- movement

Question 19

How is K+ transport handled in the thick ascending limb?

What conditions affect/regulate this?

Answer 19

• Transcellular Reabsorption
• Na+/K+/2 Cl- Cotransporter
• ​Acidosis
  
  • inhibits ROMK1 channel, blocking re-excretion of absorbed K⁺
  • ​thus increases reabsorption

Question 20

How is K+ handled in the connecting/cortical collecting ducts?

What increases this?

What inhibits it?

Answer 20

• Secretion
• Coupled with Na⁺ Reabsorption (ENaC)
• Increased by aldosterone
• Inhibited by acidosis (via ROMK1 inhibition)
  
  • thus increases reabsorption + hyperkalemia risk