Session 4: Control of Volume Flashcards

1
Q

Why does Na+ excretory rates vary?

A

Because our diet changes from day to day

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2
Q

Why would you not simply add or remove water to or from the plasma to increase ECF volumes?

A

Because that would change the plasma osmolarity and not necessarily the volume. I.e. concentration would go down and that means that water would move from the ECF to another more concentrated medium via osmosis.

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3
Q

What kind of fluid can you add to ECF to increase volume?

A

Isosmotic solution that mimics the solutes of the plasma.

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4
Q

What two modes of transport are the prominent ones in kidney reabsorption and secretion?

A

Paracellular reabsorption/secretion and transcellular reabsorption/secretion.

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5
Q

What are the two membranes concerned with kidney reabsorption and secretion?

A

Luminal/apical membrane (lumen to tubular cells) Basal/basolateral membrane (tubular cells to lateral intercellular space)

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6
Q

Main sodium transporters in the proximal convoluted tubule. Where can they be found?

A

Na-H antiporter Na-Glucose symporter Na-AA co-transporter Na-Pi Found on the apical membrane

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7
Q

What other important sodium transporter can be found in the PCT?

A

3Na/2K-ATPase NaHCO3- Both can be found on the basolateral side

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8
Q

Main sodium transporters in the loop of Henle.

A

NaKCC symporter

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9
Q

Main sodium transporters in the early distal convoluted tubule.

A

NaCl symporter

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10
Q

Main sodium transporters in the late DCT and collecting duct.

A

ENaC

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11
Q

Explain what happens in S1 of PCT.

A

The Na-glucose cotransporter move 3Na+ as well as glucose from the lumen to the tubular cells. As the glucose lvls decrease in the lumen it will have to be actively transported via this transporter. Na/K-ATPase moves 3Na+ into capillary and 2K+ is transported into tubular cells. Glucose moves into capillaries. Almost 100% of the glucose is reabsorbed here as well as the amino acids and carboxylic acids. There is also co-transport with phosphate through NaPi channels which are sensitive to PTH. Aquaporin allows movement of water.

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12
Q

What increases in concentrations in S1 of PCT?

A

Urea and Cl- concentrations. This is to compensate for the losses of glucose. The increase in Cl- concentrations create a concentration gradient for chloride reabsorption in S2-S3 of PCT.

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13
Q

Explain what transport maximum is.

A

The glucose transporters are only so many and can only work at a certain rate. If the glucose concentrations exceed this level then the reabsorption will not be able to keep up with the filtration and there will be glucose excreted. As plasma glucose increases filtration will increase linearly. But reabsorption won’t be able to keep up and excretion will happen.

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14
Q

Give examples of drugs that can act on S1 of PCT.

A

Amiloride

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15
Q

Explain how amiloride acts on S1 of PCT.

A

Amiloride is a diuretic and blocks the Na+/H+ antiporter in PCT. It also inhibits AgII on the secretion of H+ in PCT.

Amiloride has other functions in the kidneys as well.

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16
Q

Explain what happens in S2 and S3 of PCT.

A

Apical Na+ is reabsorbed via Na-H exchange.

Also Cl- begins to be transported out of the lumen via a chloride-anion antiporter.

Also chloride ions and sodium ions are transported paracellularly out of the lumen as well. This is due to a positive transepithelial charge due to the movement of Cl- transcellularly.

Water also moves out of the lumen via aquaporin.

Amino acids are also reabsorbed via sodium dependent amino acid transporters.

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17
Q

Give a summary of what is being reabsorbed in the PCT and how much.

A

65% water

100% glucose and AA

67% Na+

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18
Q

Give forces that cause reabsorption of water in the PCT.

A

Osmotic force due to sodium and glucose.

Hydrostatic force in interstitium

Oncotic force in peritubular capillary since it lost 20% of its filtrate at the glomerulus but the proteins are still left in the blood (higher conc.)

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19
Q

What happens to transporters when renal artery BP increases?

A

Reduced number of Na-H antiporters and reduced activity of Na-K/ATPase

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20
Q

What is pressure natriuresis?

A

Increased sodium excretion

21
Q

What is pressure diuresis?

A

Increased water excretion

(The two go hand in hand)

22
Q

Explain what happens in the descending limb.

A

There is an increasing concentration gradient in the kidney from cortex to papilla.

This conc. gradient allows passive paracellular reuptake of water from descending limb through loose junctions.

This causes an increase in concentration of sodium and chloride ions in the lumen of the descending limb.

23
Q

Explain what happens in the thin ascending limb.

A

The water reabsorption in the descending limb creates a gradient for passive Na+ ion reabsorption in the thin ascending limb.

The thin (squamous epithelium) allows passive reabsorption by paracellular route.

24
Q

Explain what happens in the thick ascending limb.

A

NKCC2 is a co-transporter that allows K+, Na+ and 2Cl- to exit the lumen and enter the tubular cells.

ROMK (Renal outer medullary potassium channel) is a fundamental transporter in order for NKCC2 to work. It transports K+ back into the lumen of the thick ascending limb in order for that K+ to be fed back into NKCC2 transporter.

The Na/K-ATPase is still working here.

KCl co-transporter allows K+ and Cl- to be transported into capillary and so is Cl- via another channel called ClC-Kb

25
Q

Give examples of drugs which act on the thick ascending limb.

A

Furosemide

26
Q

Explain furosemide.

A

It’s a loop diuretic which blocks the action of NKCC2. This will cause a drop in BP.

27
Q

What will happen to the NKCC2 in the macula densa cells if you give furosemide?

A

It will also block the channel here.

This causes an increased release in renin.

28
Q

Side effects of furosemide.

A

Since NKCC2 stops working there is nothing that pumps K+ back into the tubular cells so ROMK works without an opposing force.

This can lead to the patient becoming hypokalaemic.

29
Q

Summary of loop reabsorption.

A

Reabsorption of solute and water is separated.

Descending limb reabsorbs water but not NaCl

Ascending limb reabsorbs NaCl but not water.

30
Q

What can the tubule fluid leaving the loop be described as?

A

Hypo-osmotic (more dilute) compared to plasma.

31
Q

Explain the water permeability of early DCT.

A

Fairly low

32
Q

What does water permeability depend on beyond the loop of henle?

A

ADH

33
Q

Explain what happens in the early distal convoluted tubule.

A

Hypo-osmotic fluid enters.

There is active transport of Na+ (5-8%) by NCCT and then leaves via Na/K-ATPase to capillary.

The water permeability is fairly low.

34
Q

Give an example of a drug acting on the early DCT.

A

Thiazides.

35
Q

Explain the action of thiazides.

A

Blocks the NCCT.

36
Q

Why are thiazides not as effective as the other diuretics?

A

Because there is less water permeability here.

37
Q

Explain what happens in late DCT.

A

NaCl enters by NCCT and ENaC. Leaves by Na/K-ATPase.

The movement through ENaC is not electroneutral and difference drives paracellular Cl- ion reuptake.

At the end of DCT fluid is more hypo-osmotic (more diluted).

38
Q

Give examples of drugs acting on the late DCT.

A

Thiazides (NCCT)

Amiloride acting on ENaC

39
Q

What else acts on ENaC?

A

Aldosterone.

Higher levels of aldosterone will upregulate ENaC channels to increase sodium reabsorption.

40
Q

Explain the calcium reabsorption in the DCT.

A

Apical calcium transport where cytosolic calcium is bound to calbinin and shuttled to the basal membrane.

It is then transported out by NCX.

41
Q

What is the calcium reabsorption regulated by?

A

PTH and 1,25-dihydroxyvitamin D

42
Q

What can the collecting duct be divided into?

A

Cortical(CCD)

Medullary (MCD)

43
Q

There are two distinct cell types found in CCD. Which?

A

Principal cells

Intercalated cells

44
Q

Explain the function of the principal cells.

A

Active reabsorption of Na+ via ENaC on apical membrane and then let into capillary via Na/K-ATPase.

The active tranport means that no accompanying ion is needed.

This leads to a negative charge of the lumen so Cl- is taken up paracellularly.

The negative charge also causes ROMK to transport K+ out into the lumen.

45
Q

What types of intercalated cells are there?

A

A-IC (Type A) and B-IC (Type B)

46
Q

Function of A-IC

A

Secrete H+ ions

47
Q

Function of B-IC.

A

Secretion of HCO3-

48
Q
A

Ascending and Descending limbs are for some reason reversed. But numbers are in the right box.