Renal Aquaporins

Question 1

What are aquaporins?

Answer 1

Water channels found in membranes

Question 2

Why is the maintenance of strict water balance essential?

Answer 2

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

Question 3

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

Answer 3

SIADH
Diabetes insipidus

Question 4

How many membrane spanning regions do AQPs have?

Answer 4

6 with intracellular NH2 & COOH termini & internal tandem repeats

Question 5

What are proposed characteristics of the tandem repeat structures?

Answer 5

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

Question 6

What is the structure of AQP1?

Answer 6

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

Question 7

Where is AQP1 expressed?

Answer 7

PT
thin descending limb

Question 8

Where is AQP7 expressed?

Answer 8

PT apically in S3 region

Question 9

Where is AQP2 expressed?

Answer 9

Apical surface on CD

Question 10

Where are AQP3 and 4 expressed?

Answer 10

Basolateral on CD

Question 11

What part of the kidney doesn’t absorb water?

Answer 11

DCT

Question 12

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

Answer 12

presence or absence of ADH/AVP

Question 13

Where is AQP1 extremely abundant?

Answer 13

Apical plasma membrane of brush border in PT

Question 14

What happens in AQP1-deficient mice?

Answer 14

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

Question 15

What does the lack of AQP1 undermine?

Answer 15

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

Question 16

What is the main stimulus for AVP secretion?

Answer 16

High elevated plasma osmolality

Question 17

Where are osmoreceptors?

Answer 17

Supraoptic neurons
Paraventricular neurons

Question 18

When are osmoreceptors activated?

Answer 18

High plasma osmolality -> trigger AVP

Question 19

What are the supraoptic and paraventricular neurons supplied b y?

Answer 19

internal carotid artery

Question 20

What receptors does AVP bind to?

Answer 20

V2 receptor on basolateral membrane

Question 21

Which two AQPs does AVP regulate?

Answer 21

AQP2
AQP3

Question 22

What is water movement into the blood aided by?

Answer 22

Hyperosmolar gradient in medullary interstitum

Question 23

What 2 conditions are associated with increased AQP levels?

Answer 23

SIADH
NSIAD

Question 24

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

Answer 24

Anti-diuresis
euvolmic/normovolemic hyponatremia

Question 25

What happens to AVP levels in SIADH?

Answer 25

Elevated above expected

Question 26

What are 3 common causes of SIADH?

Answer 26

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

Question 27

What is hypnatremia intially mediated by?

Answer 27

ADH-induced water retention

Question 28

What does ensuring volume expansion activate in SIADH?

Answer 28

secondary natriuretic mechanisms resulting in sodium and water loss

Question 29

What are pathologic manifestations of SIADH?

Answer 29

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

Question 30

What are manifestations of NSIAD?

Answer 30

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

Question 31

What is NSIAD caused by?

Answer 31

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

Question 32

What does the V2 mutation cause?

Answer 32

V2 = hyperactivated -> inappropriate anti-diuresis

Question 33

What are conditions associated with decreased AQP?

Answer 33

Diabetes insipidus -> central or neurogenic and nephrogenic

Question 34

What is the central DI caused by?

Answer 34

Defect in AVP production or release either familial or acquired

Question 35

What is nephrogenic DI caused by?

Answer 35

Inability of kidney to respond to AVP Hereditary or acquired

Question 36

What are the major presentations of DI?

Answer 36

hypernatremia normal plasma osmolality excessive urine production

Question 37

What is the brattleboro rat disease model?

Answer 37

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

Question 38

What are the 3 most common causes of CDI?

Answer 38

head trauma infections hypothalamus tumours (may be inherited)

Question 39

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

Answer 39

concentrate urine despite normal or elevated AVP concentrations