Control Of Volume

Question 1

What does water in the ecf depend on

Answer 1

• Major osmotically effective solute in the ECF is Na+ ion
• Thus water in the ECF compartment DEPENDS on the Na+ ion content
• If sodium in ECF changes then volume of ECF changes
• Change the Na+ ion results in affect on Effective circulating volume (ECV)
• Effect BP

Question 2

How does kidney function depend on ingested sodium m

Answer 2

• Na+ ions, Cl- ions and H20 freely filtered and up to ~99% reabsorption in kidney (Energy consumption is high)
– Ingestion of sodium can vary
• E.g. low salt diet of 0.5 g/d to 20-25 g/d)
• If amount of Na+ ions in ECF were allowed to change due to diet
changes
– then amount of water in the ECF would change – thus ECV would change hence BP would change
• Therefore Kidney Na+ ion excretory rates must vary over wide range
depending on diet • The Kidney needs to match excretion of sodium to ingestion to
remain sodium balance • Urinary water excretion can be varied physiologically

Question 3

Where is sodium excreted

Answer 3

See slide

Question 4

How is water moved

Answer 4

• To change plasma volume (ECF)
– Q. Why not just add or remove water to or from the plasma
– A. because that would change the plasma osmolarity
• So ….add isosmotic solution to increase volume or remove and isosmotic solution to reduce volume without changing osmolarity
• How do we add or remove an isosmotic solution?
– No active water pumps, need to make water want to move
– The answer is therefore to move osmoles and water will follow

Question 5

Where in the nephron is sodium reabsorbed

Answer 5

PCT 67%
Ascending LOH - 255
DCT
DCT can excerpt influence on whether of not we continue to reabsorption sodium. Do I ded more sodium? Yes - reabsorption, more will follow
5% see table

Question 6

What are the effects of change in renal sodium excretion

Answer 6

• Changes in osmotic pressure and hydrostatic pressure alter the proximal tubule Na+ reabsorption (and hence water). Pressure can affect them amount of Na2+ that can be absorbed
• Proximal tubule Na+ reabsorption is stimulated by RAAS (next lecture)
• Principle cells of DCT + CD targets for the hormone aldosterone (more in next lecture)

Question 7

What is pressure naturesis and diuresus

Answer 7

• When renal artery BP INCREASES
– Reduced number of Na-H antiporter and reduced Na-K ATPase activity • Causes reduction in sodium resorption in proximal tubule • And reduction in water resorption in proximal tubule • Thus,
– Increased sodium excretion
in proximal tubule
* i.e. Pressure natriuresis – Increased water excretion
* i.e. Pressure diuresis
• ECF volume decreased and Initial BP rise diminished • NB: Pressure natriuresis and diuresis occur together – Not able to control sodium and water independently

Question 8

What is the difference between reabsorption and secretion

Answer 8

See slide

Question 9

What er the types of aquaporin

Answer 9

Hole in channel through which water can move
Aquaporin 1 - expressed all the time, water can move - water moves down conc graft - PCT and descending limb
Ascending limb - no aquaporins
DCT - no aquaporin
CD - has aquaporin 2 3 and 4. 2 is constant down the length of CD. Can be expressed on apical and basolateral surface.can withdraw them so the hole isnt all the way though - to prevent water movement - ADH regulates this.. can decide whether or not to reabsorption here

Question 10

Is sodium reabsorption activ

Answer 10

Sodium reabsorption is mainly active
• Transcellular process, driven by 3Na-2K-ATPase pumps on
basolateral membrane
• Chloride reabsorption into cell is by transcellular (active) and some
paracellular (passive). Coupled to 3Na-2K-ATPase pumps
• Na+ ion reabsorption (chloride ion is implied)

Question 11

What are different sodium transporters

Answer 11

See slide

Question 12

Describe teh different PCT segments

Answer 12

rces
Different
nephron
segments use
different apical
transporters or
channels for
transcellular
Na+
reabsorption

Question 13

In which portions of the PCT are different ions removed

Answer 13

Reabsorbing isoocmotic solution - osmolarity will not change. But composition will change - ions and water will move, but osmolarity will not change.
S1 - glucose, AA, lactate, out quickly. Then HCO3- early on
Phosphate evenkly spread all through 3 segments
Chloride lags behind everything else - in latter potions. Predominant movement is via paracellular.
Proportion of chloride gets more and more as you go on die to other ions moving out. Leaving strong chloride solution. Chloride is now higher conc in lumen than there would normally be in transcellular fluid or capillaries. Gradient of Cl- set up. This means it can be paracellular lh moved down gradient from cells into interstitium, then moved into capilalries. This creates osmotic pressure in interstitium, water follows.
By letting chloride lag behind, it doesnt require ATP

Question 14

Describe the channels in S1

Answer 14

• Basolateral 3Na-2K-ATPase • Also NaHCO3- co transporter (acids
and bases) 
• Apical
– Na H exchange 
– Co-transport with glucose 
– Co-transport with AA or carboxylic acids 
– Co-transport with phosphate (NaPi
channel sensitive to [↑PTH])
• Aquaporin 
• ** [Urea and Cl-] down S1
compensating for loss of Glucose
Increasing Cl- concentration creates
a conc. gradient for chloride
reabsorption in S2-3
Na2+ moves down conc gradt due to NaK pump. On basolateral memb Moves in on apical membrane, glucose is co transported.. secondary active a
Moving glucose against congresc gradt - due to nak pump energy - sodium gradient.

Question 15

Describe teh gradients in s2-3

Answer 15

• Basolateral 3Na-2K-ATPase 
• Apical Na+ reabsorbed in S2-S3 via Na-H exchange 
• Apical membrane has
– Na-H exchanger – Paracellular  Cl- 
– + Trans cellular chloride
• ~4mOsmol gradient favouring
water uptake from lumen 
• Aquaporin

Question 16

Compare the cells of ascending and descending limb

Answer 16

Squamous.- very permeable to water so that water can move through. - descending - assively - cells very thin
Ascending - a lot more mitochondria - indicates very active - no aquaporins

Question 17

Describe the concentrations in the descending limb

Answer 17

There is a conc grads from cortex to medulla. At cortex - isoosmoti to plasma. At medulla, very concentrated
LOH dips into concentrated medulla. So water moves from descending limb into capillaries. Drawn out by interstitial con grad- very strong in the deepest parts o f the medulla. So that fluid that enters to of DL - isosmotic - by the time it reaches bottom of descending limb - it will be very concentrated bc so much of the water has been pulled out leaving a lot of salts behind. 67% was taken out at s1. 33% still remaining. First, 10-15% of water moved out in DL - conc id very high at bottom of LOH.
• Increase in intercellular concentrations of sodium allow paracellular
reuptake of water from descending limb • This concentrates the sodium and chloride ions in the lumen of the
descending limb ready for active transport in the ascending

Question 18

Descrbe the thin ascending limb

Answer 18

• Sodium ion reabsorption passive in Thin ascending limb • Water reabsorption in descending limb creates a gradient for passive
Na+ ion reabsorption in thin ascending limb • Epithelium in thin ascending limb permits passive reabsorption by
paracellular route

Question 19

Decsribe the thick ascending limb

Answer 19

Thick ascending limb is completely impermeable to water, but has a lot of transporters. In this portion, a lot of ions. Outer medulla
• From lumen to cells via NKCC2 transporter
• Na+ ions move into interstitium due to action of 3Na-2K-ATPase
• K+ ions diffuse via ROMK back into lumen and Cl- ions move into interstitium
• In the filtrate at this point there is less K+ ions so in order to maintain activity of the NKCC2 transporter its vital the K+ diffuses back into the
filtrate
• This region uses more energy than
any other in the nephron and is
particularly sensitive to hypoxia

Question 20

Describe the gradients in the thick ascending limb

Answer 20

• From lumen to cells via NKCC2
transporter
• Na+ ions move into interstitium due
to action of 3Na-2K-ATPase
• K+ ions diffuse via ROMK back into
lumen and Cl- ions move into
interstitium
• In the filtrate at this point there is
less K+ ions so in order to maintain
activity of the NKCC2 transporter its
vital the K+ diffuses back into the
filtrate
• This region uses more energy than
any other in the nephron and is
particularly sensitive to hypoxia
NKClCl transporter on the apical membrane. 
K+ can normally diffuse bac out through the basolateral membrane. In this segment. ROMK on apical face - so potassium leaves across apical membrane so goes back into filtrate.  Potassium scarce here. So NKCC2 wont work i

Question 21

Describe loop reabsopbtion

Answer 21

• In the loop the reabsorption of solute and water is separated. • Descending limb reabsorbs water but not NaCl • Ascending limb reabsorbs NaCl but not water • For this reason ascending limb is known as the diluting segment. • Tubule fluid leaving loop is ∴ hypo-osmotic ( more dilute) compared
to plasma

Question 22

What happens beyond the loop

Answer 22

• Water permeability of early DCT is fairly low • Active Na+ ion reabsorption results in dilution • Late DCT and Collecting duct… • Water permeability is variable depending on ADH
Back in cortex Similar osmolarity similar to plasma

Question 23

What are the transporters/channels in the DCT

Answer 23

• Hypo osmotic fluid enters
• Active transport of ~5-8% of Na+
• Water permeability is fairly low
• DCV has two regions DCT 1 (early) and DCT2 ( late)
• In DCT 1 NaCl enters across apical membrane via electro- neutral NCC transporter leaves 3Na-2K-ATPase in basolateral membrane
• NB NCC transporter sensitive to Thiazide diuretics
• More hypo-osmotic fluid leaves. Further dilution

Question 24

What happens in late DCT

Answer 24

• In Late DCT 2 • NaCl enters by NCC and ENaC
leaves 3Na-2K-ATPase in
basolateral membrane • NB ENaC sensitive to Amiloride
diuretics • Movement through ENaC not
electroneutral and difference drives
paracellular Cl- ion reuptake • At the end of the DCT fluid is more
hypo-osmotic i.e. Further dilution

Question 25

What channels are acted on by diuretics

Answer 25

See slide

Question 26

What happens to calcium in the dct

Answer 26

• Apical calcium transport. • Cytosolic calcium is immediately
bound by calbindin, which shuttles
calcium to the basolateral aspect of
the DCT cell, • transported out by sodium calcium
exchanger (NCX) • Tightly regulated by hormones, such
as parathyroid hormone and 1,25-
dihydroxyvitamin D

Question 27

What are 2 cell types in the CD

Answer 27

• After DCT2 the connecting tubule CNT and early part of the collecting duct share many
similarities. Difficult to draw a line through
• Collecting Duct divided into Cortical (CCD) and medullary (MCD) regions
• Two distinct cell types Principal cells and intercalated cells found in CCD
• Division of labour amongst two cell types.
– 1) Principle cells (70% of the cells are
principal)
• Reabsorption of Na+ ions via ENaC
(same as DCT2)
– 2) A-IC and B-IC or Type B intercalated cells
• Active reabsorption of Chloride
• Intercalated cells (secrete H+ ions (A1C)
or HCO3- ions (BIC) more in acids and bases

Question 28

Decsribe the principal cells

Answer 28

• Reabsorption of Na+ ions via ENaC on apical membran
• 3Na-2K-ATPase in basolateral –driving force
• Active Na+ ion uptake through a channel and not a cotransporter means there is no accompanying anion
• produces a lumen (–) charge providing a driving force for Cl- ion uptake via paracellular route.
• This (- charge) in the lumen has an
important role in potassium secretion into
the lumen ( More later)
• Variable H20 uptake through AQP
dependent on action of ADH (more later)

Question 29

Describe the IC cells

Answer 29

• Type A intercalated cells (A-IC)
and type B intercalated cells (B-
IC). • Acid-secreting type A-IC; • Bicarbonate secreting type B-IC, • In the cortical and outer
medullary collecting duct, type
A-ICs express H+-ATPase and the
H+/K+-ATPase at the
apical/luminal membrane, • express the Cl−/HCO3−
exchanger at their basolateral
membrane.