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Physiology of Disease > Renal Aquaporins > Flashcards

Renal Aquaporins Flashcards

1
Q

What are aquaporins?

A

Water channels found in membranes

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2
Q

Why is the maintenance of strict water balance essential?

A

Keeps serum sodium conc. stable & in turn produces a stable plasma osmolality

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3
Q

What are 2 diseases that are examples of disrupted water balance mechanisms?

A

SIADH
Diabetes insipidus

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4
Q

How many membrane spanning regions do AQPs have?

A

6 with intracellular NH2 & COOH termini & internal tandem repeats

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5
Q

What are proposed characteristics of the tandem repeat structures?

A

tight turn structures that interact in the membrane forming the pathway for water translocation

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6
Q

What is the structure of AQP1?

A

tetrameric assembly of 4 identical subunits with a large glycan attached to 1

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7
Q

Where is AQP1 expressed?

A

PT
thin descending limb

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8
Q

Where is AQP7 expressed?

A

PT apically in S3 region

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9
Q

Where is AQP2 expressed?

A

Apical surface on CD

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10
Q

Where are AQP3 and 4 expressed?

A

Basolateral on CD

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11
Q

What part of the kidney doesn’t absorb water?

A

DCT

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12
Q

What does the volume of water absorbed by CD depend on?

A

presence or absence of ADH/AVP

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13
Q

Where is AQP1 extremely abundant?

A

Apical plasma membrane of brush border in PT

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14
Q

What happens in AQP1-deficient mice?

A

They are polyuric and unable to concentrate urine to more than 700mosmol
Rapidly dehydrated

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15
Q

What does the lack of AQP1 undermine?

A

Counter-current multiplication process which depends on rapid water equilibration across descending thin limb
AQP1 forms concentrated urine

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16
Q

What is the main stimulus for AVP secretion?

A

High elevated plasma osmolality

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17
Q

Where are osmoreceptors?

A

Supraoptic neurons
Paraventricular neurons

18
Q

When are osmoreceptors activated?

A

High plasma osmolality -> trigger AVP

19
Q

What are the supraoptic and paraventricular neurons supplied b y?

A

internal carotid artery

20
Q

What receptors does AVP bind to?

A

V2 receptor on basolateral membrane

21
Q

Which two AQPs does AVP regulate?

A

AQP2
AQP3

22
Q

What is water movement into the blood aided by?

A

Hyperosmolar gradient in medullary interstitum

23
Q

What 2 conditions are associated with increased AQP levels?

A

SIADH
NSIAD

24
Q

What is the major outcome on urine output of increased AQP levels?

A

Anti-diuresis
euvolmic/normovolemic hyponatremia

25
Q

What happens to AVP levels in SIADH?

A

Elevated above expected

26
Q

What are 3 common causes of SIADH?

A

neoplasia (small-cell lung carcinomas on head and neck tumors)
CNS disorders
Drug induced (anti-depressants)

27
Q

What is hypnatremia intially mediated by?

A

ADH-induced water retention

28
Q

What does ensuring volume expansion activate in SIADH?

A

secondary natriuretic mechanisms resulting in sodium and water loss

29
Q

What are pathologic manifestations of SIADH?

A

Fixed volume of cranial vault resulting in elevated ICP
dizziness, faint

30
Q

What are manifestations of NSIAD?

A

Normovolemic hyponatremia & lack of urinary dilution but low levels of AVP

31
Q

What is NSIAD caused by?

A

Mutation in AVPR2 gene encoding the V2R
change in AA 137 from arginine into cysteine or leucine

32
Q

What does the V2 mutation cause?

A

V2 = hyperactivated -> inappropriate anti-diuresis

33
Q

What are conditions associated with decreased AQP?

A

Diabetes insipidus -> central or neurogenic and nephrogenic

34
Q

What is the central DI caused by?

A

Defect in AVP production or release
either familial or acquired

35
Q

What is nephrogenic DI caused by?

A

Inability of kidney to respond to AVP
Hereditary or acquired

36
Q

What are the major presentations of DI?

A

hypernatremia
normal plasma osmolality
excessive urine production

37
Q

What is the brattleboro rat disease model?

A

decreased expression of AQP2 in rodent models reversed by chronic AVP infusion

38
Q

What are the 3 most common causes of CDI?

A

head trauma
infections
hypothalamus tumours
(may be inherited)

39
Q

What is the kidney
excessive urine production and thirst
unable to do in NDI?

A

concentrate urine despite normal or elevated AVP concentrations

40
Q
A

Physiology of Disease (15 decks)

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