Lec 6 - Control of plasma volume Flashcards

1
Q

Describe the solute composition in a 70 kg male?

A
  • 3L blood plasma.
  • 11L interstitial fluid.
  • 1L transcellular fluid
  • 28L intracellular fluid
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2
Q

Describe the important of sodium in the ECV (Effective circulating volume).

A
  • Na+ ion is the most osmotically effective solute in the ECF so water in the ECF compartment depends on the Na+ ion.
  • If sodium in the ECF changes then the volume of ECF changes.
  • A change in Na+ ion results in affect on ECV which effects BP
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3
Q

What happens if the amount of sodium ions in the ECF is allowed to change due to diet changes?

A
  • the amount of water in the ECF would change.
  • The ECV would then change, also changing the BP.
  • Therefore the kidney Na+ ion excretory rates must vary over a wide range depending on diet.
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4
Q

what stimulates the sodium reabsorption at the proximal tubule?

A

RAAS

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5
Q

What happens when renal artery BP increases?

A
  1. Renal BP increased due to the reduced number of Na-H anti porter and reduced Na-K ATPase activity in the proximal tubule.
  2. This causes a reduction in sodium reabsorption in the proximal tubule.
  3. As a result there is increased sodium excretion (e.g pressure natriuresis) and increased water excretion (e.g pressure diuresis).
  4. ECF volume decreases and initial BP rise is diminished.
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6
Q

Define reabsorption.

A

This is the movement of things in the filtrate being put back into the ECF.

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7
Q

Define secretion.

A

This is when things in the capillary are being removed.

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8
Q

What is the importance of tight junctions?

A

This is so the transporters on the basolateral face and the apical face aren’t able to interact and move.
—> The tight junction acts as a barrier.

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9
Q

Define paracellular reabsorption

A
  • This is reabsorption that goes parallel to the cell.
  • It doesn’t go via the tight junction but through loose junctions so can reabsorb water etc.
  • Overall it refers to the transfer of substances across an epithelium by passing through the intercellular space between the cells.
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10
Q

Define Transcellular reabsorption.

A
  • This is where the substances travel through the cell passing through both the apical membrane and basolateral membrane.
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11
Q

What structures are in the cortex?

A
  • PCT
  • glomerulus
  • DCT
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12
Q

What structures are in the medulla?

A
  • Loop of Henle

- The collecting duct runs through the medulla.

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13
Q

Why is there no movement of water in the DCT or ascending thin limb of the loop of henle?

A
  • doesn’t take water as there are no aquaporins.
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14
Q

What are the aquaporin channels in the Proximal tubule?

A
  • AQP 1
  • AQP 7
  • –> These are expressed all the time and keeps reabsorption isosmotic.
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15
Q

What are the aqauporin channels in the collecting duct?

A
  • AQP2
  • —-> These are constant all the way down the CD and can express one on the apical surface and one on the basolateral surface so you have a choice whether to remove one.
  • AQP3
  • AQP4
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16
Q

Describe the sodium transporters and channels that are used in the tubular reabsorption of sodium?

A
  1. Proximal tubule
    - Na-H antiporter
    - Na-glucose (symporter)
    - Na-AA co-transporter
    - Na-Pi
  2. Loop of Henle
    - NaKCC (symporter)
  3. Early Distal tubule
    - NaCl (symporter)
  4. Late Distal tubule and collecting duct
    - ENaC ( epithelial Na channels)
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17
Q

How many different regions are there in the Proximal convoluted tubule and why?

A

There are 3
- S1, S2, S3

  • This is because each region has different apical transporters or channels for transcellular Na+ reabsorption.
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18
Q

What happens in the S1 region of the PCT?

A
  • reabsorption of Glucose, amino acids and lactate is the quickest.
  • reabsorption of HCO3- also happens.
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19
Q

What channels and transporters are in the S1 region of the PCT?

A
  1. Basolateral 3Na-2K-ATPase
  2. NaHCO3- co transporter
  3. Apical transporters
    - –> Na H exchange
    - –> Co-transport with glucose
    - –> Co-transport with AA or carboxylic acids.
    - –> Co-transport with phosphate (NaPi channel sensitive to increases in the concentration of PTH)
  4. Aquaporins
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20
Q

Why would the concentration of glucose in the PCT go down during S1?

A
  • This is because glucose is being moved against its concentration gradient by using energy from 3Na 2K ATPase by movement of sodium.
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21
Q

What happens to the concentration of urea and chloride ions down S1?

A
  • They compensate for the loss of glucose.

- The chloride concentration is increased creating a concentration gradient for chloride reabsorption in S2 - S3.

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22
Q

What are the transporters/ channels in S2/3?

A
  1. Bilateral 3Na-2K-ATPase
  2. Apical Na+ reabsorbed into S2-S3 via Na-H exchange.
  3. Apical membrane has:
    - –> Na-H exchanger
    - –> Paracellular Cl-
    - –> Transcellular chloride
  4. 4mOsmol gradient favouring water uptake from lumen
  5. aquaporin
23
Q

What is reabsorption like In the plasma?

A

It is isosmotic.

24
Q

Describe the permeability of the PCT to water.

A

The proximal tubule is highly water permeable.

25
Q

What are the proportions of the substances the PCT reabsorbs?

A
  • 65% water
  • 100% glucose and amino acids.
  • 67% sodium ions.
26
Q

What is the driving force of reabsorption in the PCT?

A
  1. Osmotic gradient
    - –> This is established by solute absorption e.g. osmolarity in the interstitial spaces increases.
  2. Hydrostatic force in the interstitium increases.
  3. There is an increase in oncotic force in peritubular capillary due to loss of 20% filtrate at glomerulus but cells and proteins left in body.
27
Q

Describe the structure of the descending limb?

A
  • squamous (squashed and flat)
  • have aquaporins
  • very permeable to water.
28
Q

Describe the structure of the ascending limb?

A
  • wide lumen
  • cuboidal
  • no aquaporins so impermeable to water.
  • lots of mitochondria so are active.
29
Q

Why is the ascending limb incredibly concentrated?

A

This is because only salts are left behind as most water is being pulled out.

30
Q

Describe the transport of water from the descending limb into the peritubular capillaries.

A
  • water moves from the descending limb into peritubular capillaries as the water is drawn out by interstitial fluid.
31
Q

What happens in the descending limb?

A
  1. there is an increase in intracellular concentrations of sodium which allow paracellular reuptake of water from the descending limb.
  2. This concentrates the sodium and chloride ions in the lumen of the descending limb ready for active transport in the ascending limb.
32
Q

What happens in the thin ascending limb?

A
  1. sodium ion reabsorption is passive here.
  2. water reabsorption in the descending limb creates a gradient for passive sodium ion reabsorption in the thin ascending limb.
33
Q

What happens in the thin ascending limb?

A
  1. sodium ion reabsorption is passive here.
  2. water reabsorption in the descending limb creates a gradient for passive sodium ion reabsorption in the thin ascending limb.
  3. The epithelium in the thin ascending limb permits passive reabsorption by the paracellular route.
34
Q

What happens in the thick ascending limb?

A
  1. Na+, 2Cl- and K+ movement is from lumen to thick ascending limb cells via NKCC2 transporter.
  2. Na+ ions move into the interstitium due to action of 3Na-2K-ATPase.
  3. K+ ions diffuse via ROMK back into the lumen and Cl- ions move into the interstitium.
  4. At this point the filtrate has less K+ ions so in order to maintain the activity of the NKCC2 transporter its vital the K+ diffuses back into the filtrate.
35
Q

What does ROMK stand for?

A

Renal outer medullary potassium channel.

36
Q

What is the thick ascending limb most susceptible to?

A
  • Hypoxia , as this region uses the most energy than anywhere else in the nephron.
37
Q

Why is the ROMK channel so important?

A
  • The ROMK ensures that K+ is being secreted Inyo the filtrate as it leaves via the apical face.
  • Important as the NKCC2 transporter will not work if K+ is not secreted back into the tubule.
38
Q

What is reabsorbed in the descending limb?

A

water only

39
Q

What is reabsorbed in the ascending limb?

A

NaCl only

- as a result ascending limb is known as the diluting segment.

40
Q

Compare the tubule fluid leaving the loop of henle to the plasma?

A

Tubule fluid leaving the loop is hypo-osmotic (more dilute) compared to the plasma.

41
Q

What happens in the early stage of the DCT - DCT 1?

A
  1. Hypo-osmotic fluid enters.
  2. There is the active transport of approx 5-8% of Na+.
  3. water permeability is fairly low.
  4. NaCl enters across apical membrane via electro-neutral NCC (sodium chloride) transporter.
    - —> This leaves 3Na-2K-ATPase in the basolateral membrane.
  5. More hypo-osmotic fluid leaves, so there is further dilution.
42
Q

What is the NCC transporter sensitive to?

A

Thiazide diuretics.

43
Q

What happens in the late stage of the DCT - DCT 2 ?

A
  1. NaCl enters by NCC and ENaC leaves 3Na-2K-ATPase in the basolateral membrane.
  2. The movement through ENaC is not electroneutral and the difference drives paracellular Cl- ion reuptake.
  3. At the end of the DCT, the fluid is more hypo-osmotic e.g further dilution.
44
Q

What is the ENac transporter sensitive to?

A

Amiloride diuretics.

45
Q

Describe the apical calcium transport in the DCT.

A
  1. Cytosolic calcium is immediately bound by calbindin.
    - –> This shuttles calcium to the basolateral aspect of the DCT cell.
  2. Calcium is transported out by sodium calcium exchanger (NCX).
46
Q

What regulates the apical calcium transport in the DCT?

A

It is tightly regulated by hormones such as:

  • Parathyroid hormone
  • 1,25-dihydroxyvitamin D
47
Q

What regulates the movement of water in the collecting duct?

A

ADH

48
Q

What is the collecting duct divided into?

A
  • Cortical (CCD) regions

- Medullary (MCD) regions

49
Q

What are the two distinct cell types found in the Cortical (CCD) regions of the collecting duct?

A
  1. Principal cells - Make up about 70% of cells.

2. Intercalated cells

50
Q

What do the principal cells do?

A
  1. reabsorption of Na+ ions via ENaC on apical membrane.
  2. 3Na-2K-ATPase in basolateral - driving force..
  3. Active Na+ ion uptake happens through a channel and not a co-transporter which means that there is no accompanying anion.
    - —> This produces a lumen negative charge which provides the driving force for Cl- ion uptake via the paracellular route.
    - ———> This negative charge In the lumen has an important role in potassium secretion into the lumen.
  4. There is variable H20 uptake through AQP dependent on action of ADH.
51
Q

What are the types of Intercalated cells?

A
  • Type A intercalated cells (A-IC)

- Type B intercalated cells (B-IC)

52
Q

What do type A-IC do?

A
  • These are acid-secreting type.
  • In the cortical and outer medullary collecting duct, these express H+ - ATPase and the H+/K+ - ATPase at the apical/ luminal membrane.
  • They also express the `Cl-/ HCO3- exchanger at their basolateral membrane.
53
Q

What do type B-IC do?

A
  • These are bicarbonate secreting type.

- They also express the CL-/ HCO3- exchanger at their basolateral membrane.