Urine concentration Flashcards

1
Q

What is the average daily water intake?

A

2500 ml/day

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2
Q

How much water is lost in sweat, faeces and in airways?

A

1000 ml/day

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3
Q

How much water is lost in urine per day?

A

~1500 ml/day

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4
Q

How does the body regulate water gain/loss?

A

Changes in water excretion at the kidneys

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5
Q

What urine is produced in default?

A

Dilute urine by default

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6
Q

Is water excretion regulated independently from solute excretion? Why?

A

Yes

Daily water intake may vary independently of solute intake

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7
Q

The longer the loop of henle …

A

The more concentrated the potential produced urine can be

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8
Q

Describe the amount and concentration of urine lost in diuresis

A

Up to 20l/day

50mosm/l

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9
Q

Describe the amount and concentration of urine lost in antidiuresis

A

~0.5l/day

1200mosm/l

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10
Q

What is plasma osmolarity?

A

300mosm/l

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11
Q

What stimulates the switch between diuresis and antidiuresis?

A

ADH

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12
Q

When is ADH released, what detects this?

A

When low plasma water potential, osmoreceptor cells in the hypothalamus

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13
Q

Where is ADH stored?

A

Stored in the nerve terminals in the neurohypophysis (posterior pituitary)

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14
Q

What four main actions does ADH have?

A

Insertion of AQP2 into apical membrane of principal cells

Stimulates the NKCC channel increasing its activity

Urea transporter is upregulated

Slows the blood flow in the vasa recta

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15
Q

What is the overall effect of ADH?

A

Increases water reabsorption along the nephron to increase the osmolarity of the urine

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16
Q

What effect does increases AQP2 in principle cells have on urine?

A

Increases water permeability at the CD, more water reabsorbed, more concentrated urine

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17
Q

What effect does upregulation of NKCC have on urine?

A

More absorption of Na+ from urine in thick ascending limb

Hypo-osmotic filtrate (Na+ moved out) and hyperosmotic medullar interstitium (Na+ moved in)

More water reabsorption in CD - increases multiplier effect.

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18
Q

What effect does upregulation UT have on urine?

A

Urea diffuses out to lower water potential in medulla

Maintains interstitial hyperosmolarity

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19
Q

What effect does slowing vasa recta blood flow have on urine?

A

Reduce depletion of medullary solutes by blood flow washing out hyperosmolarity.

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20
Q

Where is AQP1 expressed?

A

PCT and descending limb

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21
Q

Where is AQP2 expressed?

A

Apical membrane of principal cells (CD), regulated by ADH

22
Q

Where are AQP3/4 expressed?

A

Basolateral membranes of CD principal cells, allowing reabsorption

23
Q

How does ADH act to increase the number of AQP2 transporters in the membrane of principal cells?

A

ADH acts on V2 receptors on principle cells of collecting duct

Activate adenylate cyclase, upregulate cAMP and activate PKA.

PKA phosphorylates cytoskeletal elements

Causes the exocytosis of AQP2 vesicles and thus the merging of AQP2 with the apical membrane to

24
Q

What is a countercurrent system?

A

Hairpin system where the flow in one limb is opposite to the flow in the other limb.

25
Q

What makes the loop of henle a countercurrent multiplier?

A

Asymmetric permeability

The descending limb of the Loop of Henle is permeable to water but the ascending limb is not.

26
Q

What initially drives the coutercurrent multiplier system?

A

Active transport of Na+ ions from the thick ascending limb.

27
Q

What transporters underpin the active transport of Na+ ions from the TALH?

A

Driven by the Na-KATPase on the basolateral membrane - generates the concentration gradient for NKCC to move Na+ from tubule lumen into the cells of Loop.

28
Q

Does TALH NKCC undergo primary or secondary active transport?

A

Secondary

29
Q

How does ADH activate NKCC?

A

ADH binds to V1 receptors which activate PLC, leads to the phosphorylation of NKCC which activates it

Faster movement of Na+ out of tubule into medulla

30
Q

What does the outflow of Na+ cause at the descending limb and why?

A

Outflow of Na+ makes the medulla interstitium more hypertonic, thus water will move out of the descending limb via osmosis.

31
Q

What happens to the concentration of tubular contents as you descend down the descending limb and why?

A

Concentration of the contents of the descending limb increases

As water moves out into the interstitium

32
Q

At what place is the contents of the tubule the most concentrated and how concentrated?

A

At the bottom of the loop it is at its most concentrated (1200msom/l).

33
Q

Why can the bottom of the ascending limb not actively transport Na+?

A

There is insufficient ATP production deep in the medulla.

34
Q

In the thin ascending limb where does Na+ move and how? Why can this happen fine?

A

Moves out of tubule passively due to high concentration gradient generated though water loss in descending limb

35
Q

Every time fluid passes through the tubule, what happens to the interstitial [Na+]?

A

Increases

36
Q

Why does the interstitial [Na+] not increase infinitely?

A

As concentration increases the gradient for reabsorption by the vasa recta increases

37
Q

In presence of ADH what is created by the LOH? What does this allow?

A

An axial hypertonic gradient is created in the medulla.

Used to extract H2O from principle cells in collecting duct, producing concentrated urine.

38
Q

How much of the inner medullary interstitial osmolarity is provided by urea?

A

50%

39
Q

Why is urea necessary?

A

Deep in the medulla the interstitium is not as hyperosmotic as it could be, because cells are metabolically limited so Na+ only moves passively .

40
Q

Where does urea move from?

A

The bottom of the collecting duct to loop of henle deep in medulla

41
Q

How does urea move out of the collecting duct?

A

Through urea transporter

42
Q

What happens to the urea once in interstitium?

A

Passively moves back into nephron or interstitium, never returns to the blood.

43
Q

What is the role of medullary blood flow?

A

Delivers nutrients

Removes reabsorbed water

44
Q

Do solutes move into descending limb?

A

In humans descending limb is slightly permeable to ions

Some evidence NaCl moves back into the descending limb which contributes to the increasing osmolarity of the nephron contents.

45
Q

Does all lost Na+ move back to the blood?

A

Na+ is reabsorbed when is it not needed to produce the hyperosmotic environment for water reabsorption.

Vasa recta slows the flow in order to prevent rapid loss of the ions to the blood to maintain reabsorption of water.

When there is no ADH present more of the Na+ is washed away.

46
Q

Why do cells of the collecting duct not get osmotically damaged?

A

Contains inert osmolites such as taurine that holds water inside the cell.

47
Q

What is the volume and osmolarity of fluid leaving the proximal tubules each minute?

A

45ml 300mOsm (1/3 not absorbed can leave)

48
Q

What is the volume and osmolarity of fluid leaving the LOH each minute?

A

25ml, 100mOsm (lower osmolarity as most ions in interstitium, ~20ml absorbed)

49
Q

What is the volume and osmolarity of fluid leaving the CD each minute in diuresis?

A

20ml, 50mOsm

50
Q

What is the volume and osmolarity of fluid leaving the CD each minute in anti- diuresis?

A

0.5ml, 1200mOsm (much water reabsorbed)

51
Q

Where is the site of passive reabsorption of urea from the nephron?

A

Medullary collecting duct