Salt Balance

Question 1

Name the solutes freely filtered

Answer 1

Na+

Cl-

H2O

• Most is reabsorbed
• These are NOT normally secreted

Question 2

Describe the first mechanism by which water and some solutes can travel from nephron lumen to blood capillaries

Answer 2

PARACELLULAR

• Generally passive and is the movement between cell spaces
• Driven by conc gradient and/or charge differences

Question 3

Describe the 2nd mechanism by which water and some solutes can travel from nephron lumen to blood capillaries

Answer 3

TRANSCELLULAR

• Specific transport protein on the apical membrane (luminal surface of cells lining nephrons)
• Transport moves the solute into the cell and from there another transporter moves the molecule across the basolateral surface out of the cell from where it is picked up by the blood
• On the luminal membrane filtered glucose and sodium are co-transported into the cell
• Glucose is moved out of the cell by facilitated diffusion across basolateral membrane while the sodium is pumped out by the sodium/potassium pump
• This figure also illustrates that the transport of many solutes including glucose is dependent on the transport of sodium
• No Na+ movement, no glucose movement

Question 4

What is linked to sodium transport

Answer 4

Chloride is also moved

Question 5

What happens to water when salt is moved from tubular lumen to blood side

Answer 5

Water follows by osmosis primarily by a paracellular route

Question 6

Process of Na+ reabsorption

Answer 6

Active, via a transcellular route and is powered by the basolateral Na+/K+ ATPase

Question 7

Process of Cl- reabsorption

Answer 7

• Paracellular (passive)
• transcellular (active)

Question 8

General principle of sodium balance

Answer 8

Increase [Na+] => increase in ECF vol

Decrease in [Na+] => decrease in ECF vol

Question 9

How do we measure salt levels

Answer 9

Indirectly through vol and pressure of ECF

• If salt level goes up, ECF goes up, BP goes up
• Increasing P means we have too much salt and should activate mechanisms to excrete salt
• Conversely decreasing P means we have too little salt and we should activate mechanisms to save/retain salt

Question 10

P_Na+

Answer 10

Plasma Na+ conc is normally constant due to ADH and thirst mechanisms

(however level can be increased - we still have excess salt in our system)

Question 11

When managing ECF vol what else do we need to manage

Answer 11

Total sodium level

Question 12

What do kidneys try to match

Answer 12

Input to output

Question 13

How much salt is ingested per day

Answer 13

8-15 g of NaCl/day

150-250 mEq/day

Question 14

What would happen if we retained salt intake for 1 day

Answer 14

Would require retention of 1L of water to maintain tonicity

Leading to an increase in BW of 1 kg

Question 15

How is Na+ excreted

Answer 15

Kidneys mainly

Skin - sweat

GIT - ver small amts in faeces

Question 16

What has a potent effect on Na+

Answer 16

Diuretic - must watch for hypotension

Question 17

Renal Na+ handling values

1. Intake
2. FIltered
3. Excreted

Answer 17

1. 150-250 mEq/day
2. 25000 mEq/day
3. 150 mEq/day

(excretion < 1% of filtered load)

Question 18

At the PCT, how much of filtered salt is reabsorbed and how

Answer 18

PCT - 65% of filtered salt is reabsorbed by BULK FLOW

Question 19

At the thick ascending limb of LOH how much of filtered salt is reabsorbed through specific transporters and how

Answer 19

25% of filtered salt is reabsorbed through specific transporters (targets of loop diuretics)

Question 20

Where is the remaining 10% of salt (in renal Na+ handling) managed

What is its reabsorption controlled by

Answer 20

in the distal nephron

Reabsorption is controlled by local and systemic actors working at the level of the distal nephron

Question 21

REGIONAL HANDLING OF Na+ Cl- AND H2O

Proximal tubule

Answer 21

Iso-osmotic reabsorption

Question 22

REGIONAL HANDLING OF Na+ Cl- AND H2O

Loop of Henle

Answer 22

Separation of salt and H2O (salt moves but water is prevented from following)

Question 23

REGIONAL HANDLING OF Na+ Cl- AND H2O

Distal tubule and collecting duct

Answer 23

Reabsorption is regulated by hormones

Question 24

Iso-osmotic reabsorption from proximal tubule

Where is the PT

Difference between interstitium of cortex and plasma

Answer 24

PT is in the cortex

Interstitium of cortex is iso-osmotic to plasma

sodium plays a key role in the movement of many other molecules

Question 25

How is Na+ balance maintained (GFR)

Answer 25

Small changes in GFR are normal and used as a way to increase the flow (reducing time for absorption) or decrease the flow (increase time for absorption) of fluid through the nephron - increase GFR =\> promote excretion of salt - decrease GFR =\> promote retention of salt

Question 26

How is RBF reduced in response to ECF vol changes

Answer 26

By sympathetic nerves, catecholamine and Ang II

Question 27

Glomerular Tubular Balance

Answer 27

Protective mechanism Ensures we always reabsorb a min essential amt of salt to maintain fluid volumes and pressures When GFR changes, the PCT reabsorbs a constant fraction of the filtered load =\> GFR increases, PCT reabsorption increases (PCT absorbs 65% of filtered salt - GTB maintains this balance even if GFR increases and filtered load increases)

Question 28

Effect of changes in GFR on PCT

Answer 28

PCT reabsorbs more than normal - 65% of a FIXED FRACTION As a result of the increased GFR we deliver 900 mEq more sodium to the LOH each day

Question 29

Effect of changes in GFR on the LOH

Answer 29

In the LOH, there is limited spare capacity We save more than normal (300 mEq more Na+) But we end up delivering approx 600 mEq more Na+ to the DCT and thus up to 600 mEq more sodium is excreted from the body due to a 10% increase in GFR Therefore changing GFR is a way to get rid of salt from the body

Question 30

Renin-Angiotensin System

Answer 30

* Multi-step pathway for maintaining ECF vol and BP * RENIN converts angiotensinogen -\> Ang I * ANGIOTENSIN CONVERTING ENZYME (ACE) converts Ang I -\> Ang II - found in endothelial cells of all BVs * Ang II (a potent vasoconstrictor that increases BP to maintain GFR in the face of a P drop) stimulates aldosterone release

Question 31

What does aldosterone do to Na+ reabsorption

Answer 31

An increase in aldosterone increases Na+ reabsorption

Question 32

Where does aldosterone come from

Answer 32

Adrenal cortex (zona glomerulosa)

Question 33

Target of aldosterone

Answer 33

Distal nephron (P cells)

Question 34

What does aldosterone affect

Answer 34

The final 5-10% of Na+ remaining in the nephron (filtrate)

Question 35

Aldosterone is secreted in response to

Answer 35

Increase in [K+] and decrease in osmolarity at adrenal cortex Indirectly via Ang II

Question 36

Mechanism of action of Aldosterone

Answer 36

Activate gene transcription of sodium channels called ENaCs and promote the insertion of these channels into the luminal membrane In this way it promotes salt conservation and retention in the body

Question 37

Major mechanisms for promoting renin release

Answer 37

All link back to a salt deficit and the need to promote salt retention

Question 38

What is responsible for promoting salt loss

Answer 38

Natiuretic hormones

Question 39

ANP - Atrial Natiuretic Peptide 1. Plasma level 2. Where is it stored 3. How is it released 4. MOA

Answer 39

1. 3-5 pM 2. Stored in granules in the myocytes of atria 3. If we have too high a salt load, the ECF vol increases and the vol of blood returning to the heart increases - super-distension of the atrial walls in response to this cuases the release of ANP 4. Works by promoting a slight increase in GFR - receptors in the brain via neural arcs appear to inhibit renin release - net effect is to promote Na+ excretion

Question 40

Hypovolemia

Answer 40

Question 41

Hypervolemia

Answer 41