Met 2: Nephro; Lec. 1 Renal Handling Of Na, K And H20

Front 1

Via what two routes can sodium be reabsorbed across the nephron?

Back 1

1) Paracellular reabsorption (passive) - between tight junctions, driven by concentration and voltage gradients. Bulk of NA moved here

2) Transcellular reabsorption (active) - two step process in which the sodium moves through the interstital space. Entry step is a passive process, but leaving the cell is an active process (ATP driven)

Front 2

What are the four sections of the nephron that reabsorb sodium and where is most of the sodium absorbed?

Back 2

1) Proximal tubule (66%)
2) Loop of Henle
3) Distal nephron
4) Collecting duct

Front 3

What are the major transport systems that handle sodium in the early proximal tubule?

Back 3

Input
1) Na+/H+ exchanger - linked to bicarbonate
2) Na+/solute cotransporter - linked to things like glucose, amino acids, lactate, phosphates

Output
1) Na+/K+/ATP pump

Front 4

What are the major transport systems that handle sodium in the late proximal tubule?

Back 4

Input
1) Na+/H+ Cl-/Base paralell exchangers - sodium is linked to chloride

Output
2) Na+/K+/ATP pump

Front 5

What are the major transport systems that handle sodium in the loop of Henle?

Back 5

Input
1) Na-K-2Cl triporter - sodium is coupled to both potassium and chloride

Output
Na+/K+/ATP pump

Front 6

What are the major transport systems that handle sodium in the early distal tubule?

Back 6

Input
1) NaCl cotransporter - no exchangers, an actual cotransporter. Every cell will have this transporter in the early distal tubule.

Output
Na+/K+/ATP pump

Front 7

What are principal cells and where are they located?

Back 7

Principal cells are the only cells in the late collecting tubule and collecting duct that reabsorb sodium.

But principle cells are found in every part of the nephron

Front 8

What are the major transport systems that handle sodium in the late distal tubule and collecting duct?

Back 8

Input
Epithelial sodium channel - allows sodium to enter via a channel.

Output
Na+/K+/ATP pump

Front 9

What increases sodium reabsorption at the proximal tubule and what do they target?

Back 9

1) Norepinephrine (NE) - targets Na+/H+ exchange and Na+/K+/ATP pump to increase reabsorption

2)Angiotensin II - targets Na+/H+ exchange

Front 10

What increases sodium reabsorption at the late distal tubule and collecting duct and what does it target?

Back 10

Aldosterone - enters nucleus, promoting the synthesis of aldosterone induced proteins, which induces the production of three things:

1) The number of sodium channels (increase input)
2) The number of Na+/K+/ATP pumps (increase output)
3) Increases mitochondrial activity, resulting in more ATP (increase output)

Front 11

What decreases sodium reabsorption at the late distal tubule and collecting duct and what does it target?

Back 11

ANP (Atrial Natriuretic Factor) - targets principal cells, increasing cyclic GMP inside the cell, binding to the sodium channel and reducing its function.

Front 12

What are the three sites in which diuretics are most effective?

Back 12

) Loop of Henle - loop diuretics (replace Cl on binding site of transporter)
2) Early distal tubule - thiazide diuretics (bind to NaCl transporter)
3) Principal cells - potassium sparing diuretics (target sodium channel, reducing activity)

Front 13

Where is the bulk of K located? Na?

Back 13

K is intracellular
Na is extracellular

Front 14

What two important hormones regulate potassium homeostasis? How do they work?

Back 14

1) Insulin - released by pancreas

2) Epinephrine - released by adrenal glands

They both work by stimulating the shift of potassium from the extracellular compartment into the intracellular compartment via the Na+/K+/ATP pump.

The serum potassium levels stabilize, followed by a gradual leakage of potassium out of the cell (via leak channels) to be removed by the kidneys.

Front 15

How is K transport different from Na?

Back 15

with Na you can only adjust the amount that is reabsorbed.

K transport you can adjust the amount that is reabsorbed AND secreted

Front 16

Where in the nephron is potassium reabsorbed and secreted?

Back 16

Reabsorbtion
1) Proximal tubule (80%)
2) Loop of Henle
3) Intercalated cells

solvent drag and paracellular diffusion
Secretion
1) Principal cells

Front 17

How is potassium excreted by the principal cells?

Back 17

1) It moves from the blood, into the principal cell via the Na+/K+/ATP pump.

2) Apical potassium channels allow potassium to leave the cell into the urine via a steep concentration gradient.

Front 18

What happens to urine potassium concentrations when you increase tubular flow? Why?

Back 18

Urine potassium levels would rise.

Increasing the tubular flow results in a higher potassium gradient for excretion. In addition, more sodium is brought into the cell, increasing the activity of the Na+/K+/ATP pump, resulting in further potassium excretion.

Plasma K concentration drives the Na/K pump. Higher the K the more active the pump

Front 19

What portions of the nephron are NATURALLY permeable to water?

Back 19

"1) Proximal tubule
2) Descending limb of the loop of Henle

They naturally contain water channels."

Front 20

What is the driving factor for water reabsorption?

Back 20

Sodium reabsorption, causing osmotic gradients.

Front 21

What drives water reabsorption by the thin descending limb of the loop of Henle if there is no sodium reabsorption in the thin descending limb?

Back 21

The sodium reabsorbed by the ascending limb is dumped into the interstitial environment, generating an osmotic gradient for water reabsorption.

Front 22

Why do potassium sparing diuretics spare potassium?

Back 22

The block the sodium channels from allowing sodium into the principal cells. This results in lower activity of the Na/K/ATP pump, causing less potassium to leave the bloodstream.

Front 23

How does the hormone ADH (vasopressin) play a role in water reabsorption along the nephron?

Back 23

It inserts water channels within the cells of the late distal tubule and collecting duct.

Front 24

What portions of the nephron will never reabsorb water, regardless if there is ADH present?

Back 24

"1) The ascending limb of the loop of Henle
2) The early distal tubule"

Front 25

Via what mechanism does ADH increase the number of water receptors in the late distal tubule and collecting duct?

Back 25

These cells have ADH receptors, leads to water channels being brought to the lumenal surface. The basolateral surface always has water channels. The half life is 15 minutes.