Sodium Control

Question 1

Of the 42L of fluid in the body where is it distributed?

Answer 1

3L in Blood plasma
11L in interstitial fluid
28L in intracellular fluid

Question 2

Why must we reabsorb both sodium and water in the kidney?

Answer 2

So that the change in volume maintains the Osmolarity of the plasma.

Question 3

What is the major osmotically effective solute in the ECF? What does it effect when it changes?

Answer 3

Na+ and it effects the circulatng volume and so blood pressure

Question 4

What must we remember about Na+ movement

Answer 4

If Na+ moves, Cl- moves as well in its own transporters.

Question 5

How is Na+ lost from the body?

Answer 5

Na+ is lost in sweat (small amount), in faeces and in urine. Sweat is hypoosmotic.

Question 6

Where is the most variable Na+ reabsorption?

Answer 6

The most variable Na+ reabsorption takes place in the distal tubule.

Question 7

How does osmotic and hydrostatic pressure of the peritubular capillaries effect sodium excretion?

Answer 7

If reduced they promote Na+ reabsorption and hence water. If they increase they inhibit Na+ reabsorption and hence water

Question 8

What are the two main effectors of Na+ reabsorption?

Answer 8

Proximal tubule Na+ reabsorption is stimulated by the RAAS

Principle cells of the DCT + CD are targets for the hormone aldosterone

Question 9

What does natriuresis and diuresis mean?

Answer 9

Pressure natriuresis - Na excretion and pressure diuresis - increased water excretion

Question 10

What is pressure natriuresis and diuresis

Answer 10

When renal BP increases, this reduces the of number of Na-H antiporters and the activity of the Na-K ATPase in the proximal tubule. Thus, there is a reduction in sodium reabsorption in PCT and a reduction in water reabsorption in PCT. This means we increase sodium excretion

Question 11

How much filtered sodium and water are reabsorbed in each of the tubules of the nephron?

Answer 11

PCT - 67% Na and 65% water.

Descending limb of LoH - 0% Na and 10-15% water

Ascending limbs of LoH - 25% Na and 0% water

DCT - about 5% Na and 0% water

Collecting duct - 3% Na and 5-24% water depending on dehydration.

Question 12

Why must Cl- also be absorbed when Na+ is absorbed?

Answer 12

Important to remember electro-neutrality. Must take with us to prevent change in charge across the membrane. Na reabsorption is an active process and as a result, indirectly so is chloride. Don’t forget that HCO3- is also reabsorbed so must balance this and Cl- with Na+ reabsorption.

Question 13

Why does the osmolarity of some ions in the filtrate increase?

Answer 13

In the PCT isosmotic solution is reabsorbed. As we take osmotically active molecules out, the ones that are left now have a high proportion in the filtrate and so a higher Osmolarity.

Question 14

Describe the absorption of Na in the S1 segment of the PCT.

Answer 14

Basolateral - 3Na-2K ATPase.

Apical – Na H exchanger, Na+ co transported with glucose, amino acids or carboxylic acids and Phosphate (NaPi transport is sensitive to PTH hormone). Aquaporin channels.

Note because of all this reabsorption we have a relative increase in concentration of urea and Cl- as we move down S1 this create a good concentration gradient for chloride reabsorption.

Question 15

Describe the absorption of Na in the S2 and S3 segment of the PCT.

Answer 15

Basolateral - 3Na-2K ATPase

Apical membrane Na-H exchanger, transcellular and paracellular chloride reabsorption (which is mostly passive process due to gradient) and aquaporin.

Question 16

Describe generally the re absorption in the PCT?

Answer 16

PCT reabsorption is isosmotic with plasma and reabsorbs approximately 65% water, 100% glucose and AA and 67% Na+. The driving force is the osmotic gradient established primarily by the NaK-ATPase, hydrostatic force in the interstitium and the oncotic force from peritubular capillaries.

Question 17

What is Glomerular tubular balance?

Answer 17

Protects the action of the PCT to always try and take that 67%. If the GFR were to increase, then there would be more left over for the rest of the nephrons and this could be damaging. So rather than take a set amount out of the filtrate the PCT takes a proportion. This occurs because there are spare transporters that aren’t always used and can be called upon if there is a change in GFR despite the normal autoregulation.

Question 18

Describe the microscopic structure of the thin and thick descending limb?

Answer 18

Thin and thick Descending limp – cells are thin, have little mitochondria and no brush border. Not involved in active transport. They are there to allow water to move with as little resistance as possible.

Question 19

What is driving the movement of water out of the descending tubules?

Answer 19

Concentration gradient moving from outer cortex to medulla driving the movement of water in the descending limb of the loop of Henle.

Question 20

After the descending limb is the filtrate still isosmotic?

Answer 20

No longer isosmotic – filtrate is now hypertonic compared to plasma.

Question 21

Which molecules diffuse in which direction in the thin ascending limb of the LoH

Answer 21

Thin ascending limb cells use that hypercontracted salt solution in the filtrate to drive passive reabsorption. This is permitted by the epithelium via the paracellular route.

Question 22

Describe and explain the transporters located in the think ascending limb of the LoH

Answer 22

This part reabsorbs actively and now has transporters. Still have the NaK-ATPase but also our primary transporter on the apical side is the NKCC2 transporter.

ROMK renal outer medullary Potassium channels are there to prevent us from running out of potassium which would cause the NKCC2 cannel would stop working.

On the basolateral side we have Cl- tranporter and then a Cl/K symporter and standard K+ channels. Finally Ca++ and Mg++ move into the interstitium paracellularly.

Question 23

What is the thick ascending limb of the LoH also known as and why is it very susceptible to hypoxia?

Answer 23

This part of the tubule is very sensitive to hypoxia as it is the must energy dependant part. Known as the diluting segment as filtrate is now hypoosmotic (more dilute than plasma)

Question 24

Describe the general re absorption tendencies of Na and water in the DCT?

Answer 24

Early DCT isn’t that permeable to water. Active Na+ reabsorption results in dilution. Late DCT and collecting duct has variable water permeability depending on ADH. This produces an even more hypoosmotic solution.

Question 25

Describe the difference between the two cells that do the reabsorption in the DCT?

Answer 25

2 sections to the tubule with two different cell types DCT1 and DCT2. They are very similar the only difference is the ENaC channel that is present on the apical membrane in DCT2.

Question 26

What transporters are present in the two cells in the DCT?

Answer 26

On the basolateral side we have Cl- tranporter and then a Cl/K symporter and standard K+ channels.

On the apical side they both have the NCC channels but only the DCT2 cell has the ENaC channel.

Note the potassium leak is now happening in the basolateral membrane and that some slight Cl- paracellular reabsorption occurs which uses the slight electro gradient created by the constant movement of Na+ reabsorption (about +30mV by the end of the DCT2.

Question 27

How is calcium reabsorbed in the DCT?

Answer 27

Calcium reabsorption (only unbound calcium is excreted) take place in the DCT. This is done by Ca++ channels on the apical membrane driven by the gradient created by a Ca++ ATPase and a Ca++Na antiporter. This is controlled by the parathyroid hormone.

Question 28

Is there a sudden change from Distal tubule to collecting duct?

Answer 28

At distal portion of distal tubule, the collecting duct and DCT look very similar and are hard to discern between. Eventually collecting duct takes on its own personality.

Question 29

Describe the 3 cell types of the collecting ducts?

Answer 29

Principle cell type 70%
ENaC and ROMK apically and the 3Na2K ATPase on the basolateral.

A-IC/B-IC type A(acid) and B(base or bicarbonate) intercalated cells.

More detail on acid/base lecture

Question 30

How is the polarity of the tubular cells maintained?

Answer 30

Note in all tubular cells there are tight gap junctions that prevent the movement of transporters, channel and pump proteins between the apical and basolateral membrane. This allows the polarity of the cell to be maintained.