Lecture 8 - Nephron Sites of Renal Sodium Reabsorption

Question 1

What determines the size of the extracellular volume?

Answer 1

Amount of sodium excreted

Question 2

Average daily sodium intake?

Answer 2

50-300 mEq/day (usually 150 mEq/day)

Question 3

Average daily sodium excretion?

Answer 3

50-300 mEq/day (usually 150 mEq/day)

Question 4

How is sodium excreted?

Answer 4

1. MAINLY urine
2. Small amount in sweat
3. Small amount in feces

Question 5

Normal daily filtration rate of Na+?

Answer 5

F = 100 mL/min x 0.140 mEq/mL = 14 mEq/min = over 20,000 mEq/day

Question 6

Normal excretion fraction for Na+?

Answer 6

0.7%

Question 7

Where is Na+ reabsorbed in the nephron? Provide %.

Answer 7

1. Proximal tubule (60%)
2. Thin ascending limb of the loop of Henle + thick ascending limb of the loop of Henle (25%)
3. Distal convoluted tubule (5-7%)
4. Collecting duct (3-5%)

Question 8

How is Na+ reabsorbed in S1?

Answer 8

1. SGLT2 with glucose
2. AA cotransporter
3. Lactate and H2PO4– cotransporters
4. Na+/H+ lumenal exchanger

=> all secondary active transport mechanisms because all driven by the Na+/K+-ATPase on the basolateral membrane

Question 9

How is Na+ reabsorption in S2 different than in S1?

Answer 9

Same as in S1, but upstream Na+ reabsorption has caused increased Cl- concentration in lumen => now there is also paracellular Cl- reabsorption which drives passive Na+ transport paracellularly

Question 10

Concentration of Cl- in S2?

Answer 10

30% higher than what it is in plasma

Question 11

Lumenal potential in S1? Explain why.

Answer 11

Slightly negative due to Na+ movement

Question 12

Lumenal potential in S2? Explain why.

Answer 12

Slightly positive due to Cl- movement

Question 13

How is Na+ reabsorbed in S3?

Answer 13

Same as in S2

Question 14

Lumenal potential in S3? Explain why.

Answer 14

Slightly positive due to Cl- movement

Question 15

How does the tubular concentration of Na+ over the plasma Na+ change throughout the proximal tubule?

Answer 15

It does NOT, because H2O moves with it at exactly the same rate

Question 16

What solutes have a tubular concentration over plasma concentration that decreases throughout the proximal tubule? What does this mean?

Answer 16

1. HCO3- (higher ratio than 2 others: reabsorbed at a lower rate)
2. AAs
3. Glucose

=> means they are being reabsorbed at a faster rate than Na+/H2O and so their lumenal concentration is plummeting

Question 17

What solutes have a tubular concentration over plasma concentration that increases throughout the proximal tubule? What does this mean?

Answer 17

1. Inulin => not reabsorbed at all

2. Cl- => not reabsorbed in S1, so lumenal concentration increases and then is reabsorbed at same rate than Na+/H2O

Question 18

What is lumenal inulin concentration indicative of? Explain why.

Answer 18

Rate of water reabsorption since it is not reabsorbed

Question 19

How is Na+ reabsorbed in the thin descending limb of the loop of Henle? Purpose?

Answer 19

NOT PERMABLE! Water moves out, Na+ lumenal concentration rises, which sets up a potential concentration gradient for the next step IF enough urea is in the interstitium

Question 20

How is Na+ reabsorbed in the thin ascending limb of the loop of Henle?

Answer 20

Simple diffusion due to the fact that the total interstitial osmolarity is the same, BUT the urea osmolarity is much higher than the NaCl, so NaCl is reabsorbed

Question 21

How is Na+ reabsorbed in the thick ascending limb of the loop of Henle? Effect on tubular fluid? Type of transport?

Answer 21

1. Basolateral Na+/K+-ATPase pumps Na+ into the peritubular capillary
2. Very unique carrier (does not utilize energy) on the lumenal surface: 1Na+/1K+/2Cl- all pumped in due to drive of sodium gradient => secondary active transport
3. Na+ pumped out via basolateral ATPase and Cl-/K+ get pumped out together by transporter or simple diffusion

=> dilution of tubular fluid because water cannot follow (TIGHT segment)

PLUS:
- Na+/H+ exchanger

Question 22

Can the unique lumenal transporter (1Na+/1K+/2Cl-) of the distal tubule be inhibited?

Answer 22

YUP - some powerful diuretics do this directly (e.g. lasix) and other block simple diffusion lumenal K+ channels, which indirectly inhibits the carrier as well

Question 23

Lumenal potential in thick ascending limb of the loop of Henle? Explain why.

Answer 23

Slight positive potential due to the fact that the pump runs out of K+ (concentration in plasma and tubular fluid much lower) so high K+ inside the cell needs to diffuse out

Question 24

How is Na+ reabsorbed in the distal convoluted tubule? What is important to note?

Answer 24

1. Basolateral Na+/K+-ATPase pumps Na+ into the peritubular capillary
2. Unique Na+/Cl- carrier (no energy required) that is sensitive to thiazide diuretics (different from those used in thick ascending limb of the loop of Henle)

Question 25

Lumenal potential in distal convoluted tubule?

Answer 25

Very negative due to Ca++ transport

Question 26

How is Na+ reabsorbed in the cortical collecting duct? How is this regulated?

Answer 26

In principal cells Na+ can enter through lumenal channels due to concentration gradient set up by the Na+/K+-ATPase on basolateral membrane

Aldosterone can regulate this channel

Question 27

Main roles of cells in cortical collecting duct?

Answer 27

1. Principal cells: NaCl reabsorption

2. Intercalated cells: acid-base balance

Question 28

Is the tubular fluid hyper or hypotonic when it passes the macula densa cells?

Answer 28

Hypotonic

Question 29

Quantitatively, how do most Na+ gain entrance into the PT cells?

Answer 29

Na+/H+ exchanger

Question 30

How is NaCl reabsorbed in the thin ascending limb?

Answer 30

Cl- transcellularly via passive diffusion and Na+ follows paracellularly