Salt Balance Flashcards
Name the solutes freely filtered
Na+
Cl-
H2O
- Most is reabsorbed
- These are NOT normally secreted
Describe the first mechanism by which water and some solutes can travel from nephron lumen to blood capillaries
PARACELLULAR
- Generally passive and is the movement between cell spaces
- Driven by conc gradient and/or charge differences
Describe the 2nd mechanism by which water and some solutes can travel from nephron lumen to blood capillaries
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
What is linked to sodium transport
Chloride is also moved
What happens to water when salt is moved from tubular lumen to blood side
Water follows by osmosis primarily by a paracellular route
Process of Na+ reabsorption
Active, via a transcellular route and is powered by the basolateral Na+/K+ ATPase
Process of Cl- reabsorption
- Paracellular (passive)
- transcellular (active)
General principle of sodium balance
Increase [Na+] => increase in ECF vol
Decrease in [Na+] => decrease in ECF vol
How do we measure salt levels
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
PNa+
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)
When managing ECF vol what else do we need to manage
Total sodium level
What do kidneys try to match
Input to output
How much salt is ingested per day
8-15 g of NaCl/day
150-250 mEq/day
What would happen if we retained salt intake for 1 day
Would require retention of 1L of water to maintain tonicity
Leading to an increase in BW of 1 kg
How is Na+ excreted
Kidneys mainly
Skin - sweat
GIT - ver small amts in faeces
What has a potent effect on Na+
Diuretic - must watch for hypotension
Renal Na+ handling values
- Intake
- FIltered
- Excreted
- 150-250 mEq/day
- 25000 mEq/day
- 150 mEq/day
(excretion < 1% of filtered load)
At the PCT, how much of filtered salt is reabsorbed and how
PCT - 65% of filtered salt is reabsorbed by BULK FLOW
At the thick ascending limb of LOH how much of filtered salt is reabsorbed through specific transporters and how
25% of filtered salt is reabsorbed through specific transporters (targets of loop diuretics)
Where is the remaining 10% of salt (in renal Na+ handling) managed
What is its reabsorption controlled by
in the distal nephron
Reabsorption is controlled by local and systemic actors working at the level of the distal nephron
REGIONAL HANDLING OF Na+ Cl- AND H2O
Proximal tubule
Iso-osmotic reabsorption
REGIONAL HANDLING OF Na+ Cl- AND H2O
Loop of Henle
Separation of salt and H2O (salt moves but water is prevented from following)
REGIONAL HANDLING OF Na+ Cl- AND H2O
Distal tubule and collecting duct
Reabsorption is regulated by hormones
Iso-osmotic reabsorption from proximal tubule
Where is the PT
Difference between interstitium of cortex and plasma
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
How is Na+ balance maintained (GFR)
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
How is RBF reduced in response to ECF vol changes
By sympathetic nerves, catecholamine and Ang II
Glomerular Tubular Balance
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)
Effect of changes in GFR on PCT
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
Effect of changes in GFR on the LOH
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
Renin-Angiotensin System
- 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
What does aldosterone do to Na+ reabsorption
An increase in aldosterone increases Na+ reabsorption
Where does aldosterone come from
Adrenal cortex (zona glomerulosa)
Target of aldosterone
Distal nephron (P cells)
What does aldosterone affect
The final 5-10% of Na+ remaining in the nephron (filtrate)
Aldosterone is secreted in response to
Increase in [K+] and decrease in osmolarity at adrenal cortex
Indirectly via Ang II
Mechanism of action of Aldosterone
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
Major mechanisms for promoting renin release
All link back to a salt deficit and the need to promote salt retention
What is responsible for promoting salt loss
Natiuretic hormones
ANP - Atrial Natiuretic Peptide
- Plasma level
- Where is it stored
- How is it released
- MOA
- 3-5 pM
- Stored in granules in the myocytes of atria
- 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
- 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
Hypovolemia
Hypervolemia
