Renal 4

Question 1

Where is 98% of our body’s potassium found?

Answer 1

In cells

Question 2

What happens if potassium homeostasis gets screwed up?

Answer 2

Nerve misfiring, cardiac arrhythmias

Question 3

In the depleted state, what portions of the nephron reabsorb potassium?

Answer 3

67% is reabsorbed in the PCT, 20% in the thick ascending loop of Henle, and 12% in the distal tubule and CD.

Question 4

Potassium reabsorption in the PCT is done completely via __________ transport.

Answer 4

paracellular

Question 5

How do thick ascending Henle cells reabsorb potassium? How does the potassium get into the interstitium? Does solvent drag happen here?

Answer 5

Into cells:

1. Paracellular transport
2. Na+/2Cl-/K+ cotransporter

Basolateral exit via diffusion

No solvent drag!

Question 6

____% of the reabsorbed potassium happens in the late distal tubule and collecting duct using the…? In which cell type does this occur?

Answer 6

12% - using the H+/K+ ATPase (2K+ are brought into the cell, 2H+ are pumped into the tubule lumen).

Intercalated cells do this.

Question 7

How do the kidneys change how much K+ they reabsorb?

Answer 7

By altering secretion in the late distal tubule and CD; K+ is always reabsorbed in the PCT and TAL (not regulated)

Question 8

What are the three mechanisms by which late distal tubule and CD cells increase K+ secretion?

Answer 8

1. Increase the activity of the apical K+ channel - allows more facilitated diffusion of K+ from the cell into the tubule lumen.
2. Increase the activity of the apical Na+ channel - allows more Na+ to be reabsorbed from the tubule lumen into the cell, pushing K+ out of the cell (both are pos. charged).
3. Increase Na+/K+ ATPase (basolateral) - gets more K+ into the cell so it can diffuse out through the apical K+ channel.

Question 9

Which cell type is responsible for K+ secretion in the late DCT and CD?

Answer 9

Principal cells

Question 10

Name the five main factors that affect K+ secretion by principal cells in the late DCT and CD.

Answer 10

1. [K+]plasma
2. Aldosterone
3. K+ channel activity
4. Na+ channel activity
5. Na+ delivery to principal cells (reabsorption)

Question 11

Some duretics decrease sodium ________ upstream of DCT and CD principal cells, which ________ (increases or decreases) potassium secretion.

Answer 11

Some diuretics decrease sodium reabsorption upstream, making the lumen in the DCT and CD less negatively charged, increasing potassium secretion.

Question 12

How does furosemide affect potassium reabsorption and secretion? Explain the two ways these are affected.

Answer 12

Furosemide inhibits potassium reabsorption via (1) inhibiting the Na+/2Cl-/K+ cotransporter in the thick ascending loop of Henle and (2) that inhibition puts more Na+ in the lumen so DCT and CD principal cells have more Na+ reabsorption –> more K+ secretion.

Therefore, Furosemide is a K+ wasting diuretic

Question 13

How does Bartter’s syndrome affect potassium reabsorption and secretion in the kidneys?

Answer 13

For the same reasons furosemide wastes K+: inhibition of potassium reabsorption via (1) inhibiting the Na+/2Cl-/K+ cotransporter in the thick ascending loop of Henle and (2) that inhibition puts more Na+ in the lumen so DCT and CD principal cells have more Na+ reabsorption –> more K+ secretion.

Question 14

How do Thiazide diuretics affect K+ secretion?

Answer 14

Thiazide diuretics inhibit the Na+/Cl- cotransporter in the early DCT (which normally reabsorb both ions). This makes the lumen have more Na+ –> more K+ secretion by DCT and CD principal cells. It is therefore a K+ wasting diuretic.

Question 15

How does Gitelman’s syndrome affect K+ secretion?

Answer 15

The same way Thiazide diuretics do: inhibition of the Na+/Cl- cotransporter in the early DCT (which normally reabsorb both ions). This makes the lumen have more Na+ –> more K+ secretion by DCT and CD principal cells.

Question 16

What are the two clinical features of Gitelman’s syndrome?

Answer 16

1. Hypotension

2. Hypokalemia

Question 17

What does Amiloride do? Does it waste K+?

Answer 17

It decreases the activity of the Na+ channel in late DCT and CD cells. This spares K+

Question 18

How does Liddle’s syndrome affect K+ reabsorption/secretion?

Answer 18

Liddle’s increases the activity of the apical Na+ channel in late DCT and CD cells –> increased Na+ reabsorption –> increased K+ secretion –> hypokalemia

Question 19

Where is most of a person’s calcium?

Answer 19

In bones

Question 20

Where does calcium reabsorption happen in a nephron?

Answer 20

70% in the PCT, 20% in the thick ascending loop of Henle, 7% in the DCT

Question 21

What are the two mechanisms of Ca2+ reabsorption in the PCT and what are their relative proportions? How is calcium transported in the thick ascending loop of Henle? What about in the DCT and CD?

Answer 21

Of the 70% of the Ca2+ reabsorption by the PCT, 80% of that occurs via paracellular transport, and 20% occurs transcellularly through apical Ca2+ channels.

Mechanisms are the same in the TAL except there is no solvent drag.

DCT and CD - transcellular transport only via Ca2+ channels.

Question 22

How do PCT cells get rid of Ca2+ on the basolateral side?

Answer 22

1. Ca2+ ATPase - it burns ATP to move the calcium across

2. Na+/Ca2+ antiporter - exchanges 3Na+ for one Ca2+

Question 23

What two hormones are released in the setting of hypocalcemia and how do they affect the kidneys?

Answer 23

Calcitriol –> increased calcium reabsorption in the DCT

PTH –> increased calcium reabsorption in the loop of Henle and in the DCT

Question 24

What does calcitonin do?

Answer 24

Released in response to hypercalcemia, it increases bone formation.

Question 25

Where is most of a person’s phosphate found?

Answer 25

86% in bones, 14% is intracellular, a tiny bit is extracellular

Question 26

How much phosphate is protein-bound (and not filtered by the kidneys)?

Answer 26

10%

Question 27

Where along the nephron is phosphate reabsorbed?

Answer 27

80% in the PCT, 10% in the DCT, 10% is excreted

Question 28

How is phosphate reabsorbed in the PCT? How does it exit cells on the other side?

Answer 28

Entry via 2Na+/PO43- cotransporter, exits via PO43-/anion antiporter

Question 29

What effect does calcitriol have on phosphate reabsorption? What about calcitonin?

Answer 29

Calcitriol increases reabsorption in the PCT.

Calcitonin decreases phosphate reabsorption in the PCT.

Question 30

What effect does PTH have on phosphate homeostasis?

Answer 30

PTH increases osteoclast activity - phosphate is released from bones, BUT this is canceled out because there is a decrease in phosphate reabsorption in the PCT. The net result is a loss of phosphate.

Question 31

Where in the nephron are organic anions and cations secreted? Are there a bunch of different transporters?

Answer 31

In the PCT. All anions compete for the same transporter, and all cations compete for the same transporter.

Question 32

How are anions secreted in the PCT?

Answer 32

They are brought into the cell with the anion/a-KG antiporter. They are secreted into the lumen with a Cl-/anion exchanger

Question 33

How does PAH increase the effectiveness of penicillin?

Answer 33

It competes for the same anion transporters in PCT cells so the penicillin isn’t cleared as quickly

Question 34

How are organic cations secreted in the PCT?

Answer 34

They enter cells via a passive transporter, and exit into the tubule in two ways:

1. cation/H+ antiporter
2. MDR-related transporter

Question 35

MDR-related transporters belong to the _____ family of transporters and these are responsible for multidrug resistance of _______ cells.

Answer 35

ABC family

cancer cells

Question 36

How are peptides and small proteins reabsorbed?

Answer 36

In the PCT via endocytosis with megalin and cubulin receptors, which is then delivered to lysosomes for degradation to AAs.

Question 37

What is Fanconi’s syndrome?

Answer 37

Defect in the megalin or cubulin receptors (for endocytosing peptides and small proteins in the PCT) or in the V-ATPase –> proteinuria.