Katz: Loop of Henle, Distal Tubule and Cortical Collecting Duct

Question 1

What are juxtamedullary nephrons?

Answer 1

Nephrons that send their loops into the medulla and consist of the descending limb and the thin and THICK ascending limb

Question 2

What is the difference between the descending limb of the loop of Henle and the ascending limb?

Answer 2

Descending limb- NO net solute transport, just WATER

Ascending limb- no permeability to water, just SOLUTE

Question 3

What happens to the concentration of solute as it passes through the loop of henle?

Answer 3

Enters from the proximal tubule at 300 mOsms.

At the lowest point it reaches 1400 mOsms.

Enters DCT at 100 mOsms.

Question 4

What type of cell if found in the TAL?

Answer 4

Big cuboidal epithelial cell

Question 5

What is the primary transporter in the TAL?

Answer 5

Na/K/2CL co transporter

Moves Na DOWN its gradient while moving K and 2Cl UP the gradient.

Question 6

Why is the osmolality of the luminal fluid in the TAL only 100 mOsms?

Answer 6

TAL has NO permeability to water. Solutes are transported out while water stays in the tube resulting in a hypo-osmolar solution.

Question 7

Describe how Na,Cl and K are ultimately reabsorbed in the peritubular capillaries from the TAL?

Answer 7

1. Na/K/2Cl co transporter brings them from the lumen into the cuboidal cell of the TAL.
2. Na/K ATPase antiporter allows Na to be reabsorbed.
3. Cl diffuses through a channel and is reabsorbed.
4. K/Cl symporter allows K and Cl to be reabsorbed.

Question 8

What percent of Na/Cl are reabsorbed in the peritubular capillaries?

Answer 8

20% of the filtered load

Question 9

What does the export of K into the lumen in the TAL do?

Answer 9

Generates a + lumen that pushes ions like Na, Ca and Mg through tight junctions.

Question 10

What is Bartter’s syndrome? What does it cause?

Answer 10

Loss of fxn of any of the transport components in the TAL

Salt wasting–> HYPOVOLEMIA
Na/K/2Cl transporters don’t work, leading to the excretion of NaCl and water. This causes the pt to pee a lot, get thirsty and become HYPOvolemic.

Question 11

What does a loop diuretic do?

Answer 11

Blocks the Na/K/2Cl co transporter in the TAL

Question 12

What are examples of loop diuretics and what are the good at treating?

Answer 12

Furosemide (lasix)

EDEMA

Most powerful!

Question 13

Where does luminal fluid move after the loop of Henle? Is it permeable to water?

Answer 13

Early distal tubule

IMPERMEABLE to water

Question 14

What is the key element in the early distal tubule?

Answer 14

NaCl symporter

Moves Na down it’s gradent while moving Cl up it’s gradient.

Question 15

What percent of filtered NaCl is reabsorbed here?

Answer 15

5%

Question 16

What is Gitelman’s syndrome?

Answer 16

Loss of function of the NaCl symporter that leads to SALT wasting.

Question 17

What drug blocks the NaCl symporter in the early distal tubule?

Answer 17

Thiazide diuretics (HCTZ)

Increase Na, Cl and Water excretion

Question 18

Thiazide diuretics are useful in treating what conditions? How do they compare to loop diuretics?

Answer 18

HTN- decrease fluid volume> decrease in BP

Only lose 5% vs. 20% so they are MILDER

Question 19

Where is Na reabsorbed in the nephron?

Answer 19

1. PCT- 65%
2. TAL- 20%
3. DCT- 5%
4. CCD- 0-4.9%
5. MCD- 5%

Question 20

What causes variable reabsorption of Na in the CCD?

Answer 20

ALDOSTERONE sensitive PRINCIPLE CELLS in the DCT and CCD

Question 21

What is the FENa when 4.9% of the filtered lad is reabsorbed in the CCD?

Answer 21

It’s possible to reabsorb 99.9% of total filtered Na so FENa is .1% and Na excretion is only 25 mM/day.

Question 22

What is the FENa when 0% of the filtered load is reabsorbed in the CCD?

Answer 22

You only reabsorb 95% of the total filtered Na so FENa is 5% and Na excretion is 1250 mM/d.

Question 23

What does the variable abosrption rate allow for in the CCD?

Answer 23

It allows for Na BALANCE across a wide range of intakes (25- 1,250 mM/d)

Question 24

What is FENa?

Answer 24

Fraction Excreted Na

Question 25

What causes a small Na?

Answer 25

Hemorrhage--> lose Na

Question 26

What is aldosterone and what effects does it have on the late distal tubule and CCD?

Answer 26

A steroid hormone that causes increased TRXN of genes leading to INCREASED expression of luminal Na and K channels as well as basolateral channels and the Na/K pump that leads to INCREASED saving of NaCl.

Question 27

What happens when aldosterone targets it's receptor?

Answer 27

``` Aldosterone enters cytosol> Aldosterone receptor complex translocates to the nucleus> binds specific SREs (steroid response elements)> Increased trxn, trln and INSERTION of: 1.luminal Na (ENaC) 2. K channels 3. Basolateral Na/K pumps > Reabosrb MORE Na ```

Question 28

What happens to FENa when more Na is absorbed?

Answer 28

FENa moves towards .1%

Question 29

What stimulates aldosterone secretion? Where is it secreted from?

Answer 29

LOW Na or HIGH K> | increased aldosterone secretion from adrenal cortical cells (zona glomerulosa)

Question 30

What leads to an increase in renin?

Answer 30

Low Na diet hypovolemia (low NaCl/H20) Low BP> BR reflex> Increased SNS activity

Question 31

How does low Na lead to an increase in aldosterone?

Answer 31

``` Low Na> increases renin> Coverts Ang to ANG I> ACE converts Ang I to Ang II> Aldosterone ```

Question 32

What is the primary secretion stimulus for aldosterone?

Answer 32

Ang II

Question 33

What are secondary aldosterone stimuli?

Answer 33

Decrease in plasma Na Increase in plasma K Increase in ACTH

Question 34

What are aldosterones actions?

Answer 34

Increased trxn, trln, insertion of the following channels in PRINCIPLE CELLS: 1. Epithelial Na channels (ENaC) and K channels (ROMK) 2. Basolateral Na/K pumps and K channels

Question 35

What are ROMK channels?

Answer 35

Aldosterone sensitive renal outer medullary K channel

Question 36

How does aldosterone cause Na to be reabsorbed? What happens to K?

Answer 36

Aldosterone> increased ENaC/K channels> brings Na into cell> Na/K ATPase allows Na to move into the ISF> reabsorbed into the peritubular capillaries K is secreted into the lumen and the ISF.

Question 37

What is Type I pseudo-hypoaldosteronism?

Answer 37

Loss of function of luminal epithelial Na channels (ENac) in principle cells or collecting duct cells. This leads to SALT WASTING.

Question 38

What is Liddle's syndrome?

Answer 38

Gain in fuctionof the ENaC d/t inefficient removal from cell surface (can't get rid of ENaC)> always reabsorb Na> HTN, Edema, hypevolemia

Question 39

What is salt sensitive HTN?

Answer 39

Liddle syndroome Can't get rid of ENaC channels so you over reabsorb water/Na.

Question 40

What does Amiloride do?

Answer 40

Blocks ENaC channels.

Question 41

What leads to an increase in renin?

Answer 41

1. Low Na diet/low body NaCL> sensed at JGA via load or delivery signal mediated by macula densa cells 2. Hypovolemia> aff arteriolar baroreceptor 3. Increased SNS activity 4. Low circulating Ang II

Question 42

What secretes renin?

Answer 42

Granular cells located in the JGA located in the aff arterioles

Question 43

What are the many actions of Ang II?

Answer 43

1. Aldosterone secretion 2. VASOCONSTRCITOR 3. Na/H exchange to reabsorb more Na 4. Vasopressin> reabsorb more water 5. Increases SNS activity by Ang II binding to cicumventricular organs

Question 44

What happens when ang II is too high for a situation?

Answer 44

GROWTH: LV hypertrophy Glomerular sclerosis (collapse of glomerular capillaries> decreased GFR)

Question 45

What are the three mechanisms used to maintain Na balance?

Answer 45

1. GFR 2. Principal cells and aldosterone 3. Proximal Na/H antiporter activity

Question 46

How does GFR respond to high Na?

Answer 46

Hi Na intake> GFR/filtered load of Na increase> Increase Na EXCRETION.

Question 47

How does aldosterone respond to high Na?

Answer 47

Hi Na intake> aldosterone levels fall> Na reabsorption falls> Na EXCRETION increases

Question 48

How does the proximal Na/H antiporter activity respond to high Na intake?

Answer 48

``` Hi Na intake> renin, angII, NE fall> proximal Na/H antiport activity decreases> Na reabsorption falls> Na excretion increases ```

Question 49

How do ANP and BNP help to maintain Na balance?

Answer 49

Both cause increased Na excretion ``` High salt intake> distension of atria/increased EDV> ANP/BNP secretion increase> aff arteriole dilation/inhibition of renin secretion/direct tubular actions> GFR/filtered load of Na increase> Na reabsorption falls> Na excretion increases ```

Question 50

Where do ANP and BNP come from?

Answer 50

ANP- atria BNP- ventricles

Question 51

How do you calculate RPF?

Answer 51

Flow in Aff arteriole x plasma Na

Question 52

How do you calculate the filtered load of Na?

Answer 52

GFR x plasma Na

Question 53

How do you calculate the concentration of Na in the eff plasma flow?

Answer 53

Eff flow x conc of Na

Question 54

How do you calculate the Na reabsorptive rate?

Answer 54

Filtered load of Na- Na excretion rate

Question 55

How do you calculate the Na excretion rate?

Answer 55

Urine flow x urine Na concentration

Question 56

How do you calculate FENa?

Answer 56

Na excreted/ Total filtered load of Na

Question 57

How do you calculate Na clearance?

Answer 57

Excretion rate/ concentration of Na in the plasma