LOH, Distal Tubule and Cortical Collecting Duct

Question 1

What are the two types of nephrons based on LOH size and location? Which do we care about?

Answer 1

justamedullary nephrons and cortical nephrons

we care about juxtamedullary nephrons because their loops dip deep into the medulla

Question 2

What happens to the extracellular fluid osmolarity as you do deeper into the medulla?

Answer 2

It increases in osmolarity drastically - from 300 mOsm at the corticomedullary junction to nearly 1400 mOsms at the lowest point

Question 3

How does this increase in osmolarity of the extracellular fluid mean for the function of the descending loop of henle?

Answer 3

It’s primary purpose is for H2O reabsorption - the high osmolarity sucks the water out thorugh aquaporins

Question 4

Is there also solute movement into the extracellular space from the descending loop of henle?

Answer 4

nope - just water

Question 5

If there is no solute movement form the descending loop of henle, what happens to the osmolarity inside the loop?

Answer 5

It also goes up drastically - reaching 1400 mOsms in balance at the base

Question 6

What is the function of the ascending loop in comparison to the descending loop.

Answer 6

In the ascending loop there are channels and pumps for solute movement, but no aquaporins. So here solutes are reabsorbed, but water isn’t

Question 7

What’s the new pump found on the luminal membrane of the ascending limb of the LOH?

Answer 7

the Na+/K/2Cl co-transporter

Question 8

What happens to the Na+ that’s pumped into the cell by the Na+/K/2Cl co-transporter?

Answer 8

It’s pumped out to the extracellular fluid via the Na/K atpase

Question 9

What happens to the K+ that’s pumped into the cell by the Na+/K/2Cl co-transporter

Answer 9

It builds up and then gets either pumped into the extracellular fluid with the K+Cl- symporter or some leaks back into the luminal fluid via a K channel

Question 10

What happens to the 2 Cl_ that are pumped into the cell by the Na+/K/2Cl co-transporter

Answer 10

Some of it goes into the extracellular fluid via the K+/Cl- symporter and some diffuses down its concentration gradient via Cl channels

Question 11

There is another way for Na+ to get to the extracellular fluid from the lumen in the ascending limb. How?

Answer 11

Goes through tight junctions (remember that the Na+, K+ and 2 Cl- balance the charge transport through the cotransporter, but some K+ leaks back into the lumen, making the lumen a bit too positively charged for Na+’s liking.)

Question 12

What percentage of NaCl filtered load is reabsorbed in the ascending limb?

Answer 12

about 20%

Question 13

What happens to the osmolarity of the extracellular fluid outside of the ascending loop?
What happens to the osmolarity of the filtrate inside the ascending loop?

Answer 13

the osmolarity increases in the extracellular fluid because there’s only solute reabsorption and no H2O reabsorbtion

the osmolarity of the filtrate goes down because of the same reason

Question 14

What is the osmolarity of the filtrate once you reach the top of the ascending loop?

Answer 14

only 100 mOsms

Question 15

Loss of function of any transport component in the ascending limb will result in what syndrome/

Answer 15

Bartter’s syndrome

Question 16

What happens in Bartter’s syndrome?

Answer 16

salt wasting - you don’t get salt reabsorbtion, so you excrete too much Na and Cl. Water follows solute so you also have diuresis and hypovolemia

Question 17

What drug will essentially cause a Bartter’s syndrome/

Answer 17

loop diuretics = furosemide or bumetanide

Question 18

What is the brand new transporter in the early distal convoluted tubule/

Answer 18

the luminal NaCl symporter

uses secondary active transport with Na moving down it’s concentration gradient and bringing Cl with it

Question 19

What blocks the luminal NaCl symporter in the early distal convoluted tubule?

Answer 19

thiazide diuretics

Question 20

Loss of function of the NaCl symporter causes what syndrome? Symptoms?

Answer 20

Gitelman’s syndrome?

salt wasting and hypovolemia - but not nearly as bad as Bartter’s syndrome because only 5% of NaCl is reabsorbed here instead of the 20% from the ascending limb

Question 21

Moving on to the late distal convoluted tubule and the cortical collecting duct….How much Na is reasbored there?

Answer 21

It’s variable! Ranges from 0 to 4.9%

Question 22

How is Na+ reabsorbtion in the cortical collecting duct regulated?

Answer 22

aldosterone-sensitive principal cells are located in this area

aldosterone promotes Na reabsorbtion

Question 23

If the range of Fractional Excretion of Na ranges from 0.1% to 5%), and a total filtered load of Na being 25,000 mM/day, what is the normal range of Na excreted in the urine?

Answer 23

25 mM/day to 1250 mM/day

used to keep us in Na balance. If we eat a lot of sodium, Aldosterone release goes down and we excrete more sodium

Question 24

About how much Na is reabsorbed from the medullray collecting duct?

Answer 24

about 5%

Question 25

Where is aldosterone secreted from?

Answer 25

the adrenal cortical cells = zona glomerulosa

Question 26

What are the triggers for aldosterone secretion?

Answer 26

low sodium or high potassium
also angiotensin II, which is increased when renin is released (triggered by low Na+, hypovolemia or increased sympathetic nervous system)

Question 27

How does aldosterone work?

Answer 27

it’s a steroid, so it binds to the receptor and the aldosterone receptor complex translocates to the nucleus and binds to steroid response elements on the DNA to increase transcription, translation and insertion of necessary channels and transporters

Question 28

What channels and transporters are increased with aldosterone?

Answer 28

1. luminal Na+ channels (ENaC)
2. luminal K channels
3. basolateral Na/K ATPases
4. basolateral K channels

Question 29

What is the name of the aldosterone-sensitive luminal K channels?

Answer 29

the renal outer medullary K channel = ROMK

Question 30

What happens in Type 1 pseudo-hypoaldosteronism?

Answer 30

it’s loss of function of the luminal ENaCs in the principal cells. This means you don’t get Na reabsorbion and you have salt wasting and hypovolemia

Question 31

What happens in Liddle’s syndrome?

Answer 31

An issue with transporter trafficking where the cell can put ENaCs up when aldosterone is high, but it can’t receycle them away frm the membrane when aldosterone is low, so you just constantly reabsorb salt

you get salt-sensitive hypertension, hypervolemia and edema

Question 32

What are the triggers for Renin release from the juxtamedullary cells of the afferent arteriole? There are 4…

Answer 32

1. low Na+ sensed at the juxtamedullary apparatus
2. hypovolemia sensed at the afferent arteriolar baroreceptors (the juxtamedullary cells again)
3. high symapthetic nerve activity (induced by other baroreceptors from hypovolemia)
4. low circulating angiotensin II

Question 33

What are the 5 things angiotensin II does?

Answer 33

1. stimulates aldosterone secretion
2. vasoconstrictor
3. proximal Na+/H+ exchange to reabsorb more Na+
4. Vasopressin release to increase H2O reabsorption
5. increases sympathetic nervous activity

ultimately, it wants to save salt, save water, save volume and save BP

Question 34

If angiotensin II is too high for the situation, what happens?

Answer 34

it starts to act like a growth factor, specifically, you get left ventricular hypertrophy and glomerular sclerosis

Question 35

What happens to GFR as salt intake increases?

Answer 35

it also increases - higher salt means high plasma volume, which means higher pressure in the glomerulus with higher GFR and higher creatinine clearance

Question 36

What happens to Na excretion with increased salt intake? How about serum sodium concentration?

Answer 36

excretion increases, but serum concentration actually doesn’t change that much = Na balance!

Question 37

What happens to body weight with increased slat intake?

Answer 37

increases - because extracellular fluid volume increases (edema)

Question 38

What happens to renin activity with increast salt intake?

Answer 38

decreased

Question 39

What happens to plasma aldosteron with increased salt intake?

Answer 39

decreased

Question 40

What happens to systolic and diastolic BP with increased salt intake?

Answer 40

nothing much at all - so sodium doesn’t have much effect on epople who don’t have HTN or salt-sensitivity

Question 41

Does intracellular fluid go up with increased NaCl intake?

Answer 41

nope - remember - Na/KATPase

Question 42

So…what are the four major renal mechanisms to stay in Na+ balance?

Answer 42

1. GFR and hence the filtered load of Na+ - will increase with increased salt intake
2. principal cells have aldosterone directed increases in Na+ reabsorption
3. Proximal Na/H antiporer activity increases in direct responseto renin-angiotensin system and sympathetic nerves or NE
4. ANP and BNP cause increased Na excretion (dilates afferent arteirole to increase GFR and filtered load of Na)