Renal Aquaporins Flashcards
What are aquaporins?
Water channels found in membranes
Why is the maintenance of strict water balance essential?
Keeps serum sodium conc. stable & in turn produces a stable plasma osmolality
What are 2 diseases that are examples of disrupted water balance mechanisms?
SIADH
Diabetes insipidus
How many membrane spanning regions do AQPs have?
6 with intracellular NH2 & COOH termini & internal tandem repeats
What are proposed characteristics of the tandem repeat structures?
tight turn structures that interact in the membrane forming the pathway for water translocation
What is the structure of AQP1?
tetrameric assembly of 4 identical subunits with a large glycan attached to 1
Where is AQP1 expressed?
PT
thin descending limb
Where is AQP7 expressed?
PT apically in S3 region
Where is AQP2 expressed?
Apical surface on CD
Where are AQP3 and 4 expressed?
Basolateral on CD
What part of the kidney doesn’t absorb water?
DCT
What does the volume of water absorbed by CD depend on?
presence or absence of ADH/AVP
Where is AQP1 extremely abundant?
Apical plasma membrane of brush border in PT
What happens in AQP1-deficient mice?
They are polyuric and unable to concentrate urine to more than 700mosmol
Rapidly dehydrated
What does the lack of AQP1 undermine?
Counter-current multiplication process which depends on rapid water equilibration across descending thin limb
AQP1 forms concentrated urine
What is the main stimulus for AVP secretion?
High elevated plasma osmolality
Where are osmoreceptors?
Supraoptic neurons
Paraventricular neurons
When are osmoreceptors activated?
High plasma osmolality -> trigger AVP
What are the supraoptic and paraventricular neurons supplied b y?
internal carotid artery
What receptors does AVP bind to?
V2 receptor on basolateral membrane
Which two AQPs does AVP regulate?
AQP2
AQP3
What is water movement into the blood aided by?
Hyperosmolar gradient in medullary interstitum
What 2 conditions are associated with increased AQP levels?
SIADH
NSIAD
What is the major outcome on urine output of increased AQP levels?
Anti-diuresis
euvolmic/normovolemic hyponatremia
What happens to AVP levels in SIADH?
Elevated above expected
What are 3 common causes of SIADH?
neoplasia (small-cell lung carcinomas on head and neck tumors)
CNS disorders
Drug induced (anti-depressants)
What is hypnatremia intially mediated by?
ADH-induced water retention
What does ensuring volume expansion activate in SIADH?
secondary natriuretic mechanisms resulting in sodium and water loss
What are pathologic manifestations of SIADH?
Fixed volume of cranial vault resulting in elevated ICP
dizziness, faint
What are manifestations of NSIAD?
Normovolemic hyponatremia & lack of urinary dilution but low levels of AVP
What is NSIAD caused by?
Mutation in AVPR2 gene encoding the V2R
change in AA 137 from arginine into cysteine or leucine
What does the V2 mutation cause?
V2 = hyperactivated -> inappropriate anti-diuresis
What are conditions associated with decreased AQP?
Diabetes insipidus -> central or neurogenic and nephrogenic
What is the central DI caused by?
Defect in AVP production or release
either familial or acquired
What is nephrogenic DI caused by?
Inability of kidney to respond to AVP
Hereditary or acquired
What are the major presentations of DI?
hypernatremia
normal plasma osmolality
excessive urine production
What is the brattleboro rat disease model?
decreased expression of AQP2 in rodent models reversed by chronic AVP infusion
What are the 3 most common causes of CDI?
head trauma
infections
hypothalamus tumours
(may be inherited)
What is the kidney
excessive urine production and thirst
unable to do in NDI?
concentrate urine despite normal or elevated AVP concentrations
