Control of Blood Volume Flashcards
What ion usually goes along with Na+ to maintain electroneutrality?
Cl-
Why not just add/remove water to or from the plasma to change its volume?
Because that would change the plasma osmolarity
Where in the nephron does the majority of sodium reabsorption occur?
Proximal tubule
Describe the fluid that leaves the proximal tubule in terms of its osmolarity
Isosmotic - because as ions are reabsorbed, water is also reabsorbed maintaining the osmolarity of the fluid in the PCT
Describe the permeability of the thin descending limb of the loop of henle
Very permeable to water, less to ions
What is proximal tubule Na+ reabsorption stimulated by?
RAAS
When renal artery BP increases, what causes reduction in sodium reabsoption in the proximal tubule?
Reduced number of Na-H antiporter and reduced Na-K-ATPase activity
Where is all the glucose and amino acids reabsorbed?
PCT
Where is the majority of sodium, chloride and potassium reabsorbed?
PCT
What are the two routes through which reabsorption can take place?
Transcellular - through a cell
Paracellular - via the intercellular space between cells
What is the main transporter in the PCT on the basolateral side of cells?
3Na-2K-ATPase
What does the basolateral side of cells face?
Faces the interstitium
What does the apical membrane face?
Lumen
Describe what the NaKATPase does in the tubule
Pumps out Na+ ions using active transport
This creates an electrochemical gradient which favours the movement of Na+ into the cell from the apical side
Where in the nephron are there NO aquaporins present?
Ascending limb of the loop of henle
Where are AQP1 channels present?
PCT and descending loop of henle
Where are AQP2, AQP3 and APQ4 channels present?
Collecting ducts
What channels are present in the proximal tubule that involve sodium?
1) Na-H antiporter
2) Na-Glucose symporter
3) Na-AA co-transporter
4) Na-Pi
What are the three regions of the proximal tubule and how are these divided?
S1, S2, S3
Pars convolute resides in cortex, divided into S1 and proximal part of S2
Pars recta resides in outer medulla - makes up distal part of S2 and S3
What is the S1 segment of the proximal tubule impermeable to and what is the significance of this?
Not permeable to urea and Cl-
Their concentration increases in S1 which creates a concentration gradient which is used in the S2 and S3 segments.
In S2 and S3, Cl- can be transported from the lumen of the tubule into the peritubular capillaries either paracellularly or transcellularly down their concentration gradient
How is glucose reabsorbed in the proximal tubule?
Transported across apical membrane against their concentration by co-transport - SGLUT transporters move glucose with 2 sodium ions. Then, glucose crosses the basolateral membrane via facilitated diffusion.
How are amino acids reabsorbed in the proximal tubule?
Na+/amino acid symporters are present on the apical side of cells in the S1 segment which reabsorbs all the amino acids
What does the Na+/H+ antiporter do in the PCT?
Moves Na+ ions in to the tubular cells and expels H+ into the tubule (maintains pH)
How is sodium reabsorbed in the S1 segment of the PCT?
1) Na-H exchange
2) Co-transport with glucose (SGLT2)
3) Co-transport with amino acids
4) Co-transport with phosphate
On which membrane is Na-K-ATPase located?
Basolateral
On which membrane is the SGLT transporter located?
Apical
Which is the primary site of sodium reabsorption in the loop of henle?
Thick ascending limb
How is sodium absorbed in the thick ascending limb?
Via NKCC2 on the apical membrane
How does the NKCC2 transporter work?
Moves one sodium ion, one potassium ion and two chloride ions across the apical membrane
How does the sodium potassium ATPase on the basolateral membrane establish an electrochemical gradient?
By pumping 3 sodium ions out of the cell and 2 potassium ions into the cell - creating a low intracellular concentration of sodium and also making the inside of the cell negatively charged (meaning sodium can move down its electrochemical gradient through transporters on the apical membrane)
In the thick ascending limb, how are potassium ions transported back into the tubule?
Via ROMK channels (prevents toxic build up of potassium within the cell)
In the thick ascending limb, how are chloride ions transported out of the cell into the tissue fluid?
Via CIC-KB channels
How does water reabsorption occur in the thin descending limb?
Passively, via AQP1 channels
No sodium reabsorption
What is Bartter syndrome?
Genetic condition caused by mutations in the genes that code for the NKCC2 transporter, apical potassium channel or basolateral chloride ion channel. This results in decreased NaCl reabsorption
Leads to hypokalaemia because more sodium being reabsorbed in the distal tubule leading to increased excretion of K+
Leads to hypovolaemia as decreased reabsorption of NaCl means less osmotic pressure
What can be used to treat hypertension by inhibiting the NKCC2 transporter in the thick ascending limb?
Loop diuretics
How do loop diuretics work?
Inhibit NKCC2 in the thick ascending limb
Increase excretion of NaCl in the urine
Reduces water absorption
Therefore reduces plasma volume
Describe the histology of PCT cells
- Brush border
- Large outside diameter
- Lots of mitochondria
Where does sodium reabsorption occur in the nephron?
PCT, ascending loop of henle, DCT and collecting duct
What happens when all the glucose transporters are saturated with glucose?
Glucose goes in the urine
When are glucose transporters fully saturated?
At 11 mmol/L
On which membrane is ROMK found in the thick ascending limb?
Apical membrane
On which membrane is NKCC2 found in the thick ascending limb?
Apical membrane
What drug inhibits the action of the Na-H exchanger in the PCT?
Amiloride
What transporter is regulated by parathyroid hormone?
Sodium dependent phosphate transporter in the proximal tubule
How is albumin reabsorbed in the proximal tubule?
Albumin taken in to tubular cells via receptor mediated endocytosis
Then lysosome breaks it down into its amino acids and the amino acids are transported into the capillary via passive amino acid transporters
What happens to the K+ and Cl- after they are taken into the cell with sodium via NKCC2 in the thick ascending limb?
K+ diffuse via ROMK back into lumen
Cl- ions move into interstitium
In the thick ascending limb, why is it vital that K+ diffuses back into the filtrate after entering tubular cells via NKCC2?
In order to maintain activity of NKCC2
Otherwise there would be a lower concentration of K+ in the lumen so K+ would want to move from the tubular cells into lumen rather than the other way around
Why is the ascending limb known as the diluting segment?
Because the ascending limb reabsorbs NaCl but not water
Descending limb reabsorbs water but not NaCl
Describe the osmolarity of the tubule fluid leaving the loop
Hypo-osmotic (more dilute) compared to plasma
What is the role of the early DCT?
Absorption of ions, including Na+ , Cl- and Ca2+
How does NaCl enter across the apical membrane in the early DCT?
Via electroneutral NCC transporter
What drug acts on the NCC transporter in the DCT?
Thiazides
What transporter does amiloride target?
ENaC in DCT
How does NaCl enter and leave the tubular cell in the late DCT?
Enters via NCC and ENaC on the apical membrane
Leaves via NaKATPase on the basolateral membrane
What diuretics is ENaC sensitive to?
Amiloride
Is movement through ENaC electroneutral?
No, difference drives paracellular Cl- ion reuptake
Describe the osmolarity of the fluid leaving the DCT
More hypo-osmotic - further dilution has occurred
Where is a major site of calcium reabsorption?
DCT
Describe calcium reabsorption in the DCT
There is apical calcium transport - then cytosolic calcium immediately binds to calbindin which shuttles calcium to the basolateral aspect of the DCT cell.
It is then transported out via NCX
What are the two main types of cell found in the collecting duct?
Principal cells and intercalated cells
How do principal cells of the CD reabsorb sodium?
Via ENaC
What do intercalated cells do?
Secrete either H+ or HCO3- to alter blood pH
What does spironolactone do?
Acts as an antagonist of aldosterone receptor in the collecting duct - reduces sodium reuptake
