Water Balance Flashcards
what receptor does ADH bind in the kidneys
what kind of R
where
V2
GPCR
collecting ducts and distal tubule
what are the ADH receptors and where are they
V1a - blood vessels: vasocronstriction
V2 - principle cells in renal collecting ducts: increased AQ2 on apical membrane
V3 (=V1b) - anterior pituitary: increases ACTH secretion
Regulatory of ADH secretion
Osmolality»_space;> Volume > Pressure
○ 1% increase in Osm = AVP release
○ 10-fold higher required for V/P
- Baroreceptors (carotid, aorta)
- atrial stretch receptors
- plasma tonicity
- Pain, nausea
○ Ex head injury
what inhibits ADH release
- GABA
- Dynorphin
- Somatostatin
effect of lithium on ADH?
inhibits action of AQ2 going on cell membrane after ADH binding to R
HyperCa effect on ADH?
inhibits action of AQ2 going on cell membrane after ADH binding to R
Plasma osmolality - what is it and how to calc
Plasma Osmolality = Osmotically active molecules in plasma
2 x [Na+] + 2 x [K+] + Glucose
SNS HypoNa
Seizures
Coma
Confusion/disorientation
Gait instability
Tremor
Asterixis
Myoclonus
Dysarthria
Muscle weakness
Cheyne-stokes respiration
HypoNa -first labs to rule out
HyperBG
HyperTG
Hyperproteinemia
HypoNa - volume status normal/high DDx
Urine Osm <200:
- Hypothyroidism
- GC def
- Nausea
- SIADH
- Carbamazepine, cyclophosphamide, vinblastine
Urine Osm >200:
- Psychogenic polydipsia
- Water intoxication
HypoNa - hypovolemic DDx
Urine Na >30
- Diuretic
- MC def
- Kidney disease (CKD, polycystic kidney)
- CSW
- Na administration
Urine <30
- non renal loss w XS water intake
- hypovolemic dehydration
- CHF
- Nephrotic syndrome
- Cirrhosis
- PPV
HypoNa - look at volume status and then what?
If hypovolemic -> look at urine SODIUM
– because it’s a water problem and that means you look at the Na
If eu-/hypervolemia -> look at urine OSM
what deficiencies decrease water excretion
Hypothyroidism and adrenal insufficiency
when present may mask diabetes insipidus
HyperNa - Ddx for hypovolemia
XS free water loss:
- Renal
– DI (C/N)
—osmotic diuresis w nonNa solute
— tubulopathy
- GI
—Diarrhea, emesis, stromal loss
- Derm
—burns
—sweating
- Premature neonates
- Pulmonary
—tachypnea
—mech vent
- AVP antagonist (captains)
Inadequate free water intake:
- inability to BF
- inadequate IVF in very sick kids
- neurologically impaired children w inability to communicate
- adipsia
HyperNa - Ddx for N/hi volume status
Na overload (usually w impaired/immature renal fn)
- Infants concentrated formula
- Infusion hypertonic saline
- Salt poisoning (munchausen by proxy)
Ddx polyuria
- Central DI
–congenital, LCH, germinoma, autoimmune hypophysitis - Congenital nephrogenic DI
- Pregnancy induced DI
- Hypercalcemia
- Diuretic use
- Glucocorticoid use
- Diabetes mellitus
- Primary polydipsia
- HyperCa
- HypoK
- Fluid overload (ex post op)
- Polyuric phase of renal failure or AKI/ATN
- Cerebral salt wasting
- UTI
- Mannitol
- Infiltrative renal diseases (e.g. histiocytosis)
- Low sodium intake (diminished tonicity of renal medullary interstitium and NDI)
- Decreased protein intake (diminished tonicity of renal medullary interstitium and NDI)
- Sickle cell nephropathy
- Lithium
what is nephrogenic SIADH
- what is it
- gene
- labs to differentiate from other SIADH
extremely rare mutation of the V2 receptor producing chronic activation
AVP2R gene
would have low AVP/copeptin level
Meds causing SIADH
- Desmopressin
- SSRI, TCA, MOA
- Chemo (cisplatin, cyclophosphamide, vincristine, vinblastine)
- Anti-epileptic (carbamazepine)
- Ecstasy
Diagnostic Criteria
- Hyponatremia <134
- Hypoosm <280
- Euvolemia
- High urine Na >40
- inappropriate conc urine for hypoNa >100
- Excluded AI
- Excluded hypothyroid
- Excluded diuretic use
Tx options for SIADH
- 3% saline if sx’atic
- fluid restrict
- Loop diuretics (furosemide) - preferentially excrete free water over sodium or potassium
- Sodium supplementation
- Vaptans -> ADH-R antagonist
DI Criteria
Pathlogic polyuria and polydipsia >2L/m2/day
AND
(EITHER Serum osm >300 and/or Na >145 with urine Osm <300
OR water dep w serum osm >300 and/or Na >145 with urine osm <600 and NOT rising despite plasma osm rising)
Causes of CDI
- surgery
- trauma
- cranio
- germinoma
- infiltration: LCH, sarcoid, mets
- autoimmune
- Idiopathic
- Drugs: Ethanol; Phenytoin; Opiate antagonists; Halothane; Alpha-adrenergic agents
- Congenital hypopituitarism
- Familial
— AD mutation in ADH: magnocellular cell death by the accumulation of misfolded AVP precursors within the endoplasmic reticulum (“toxic gain of function”)
— AR mutation in ADH: early onset polyuria and hypernatremia
—Wolfram syndrome (DIDMOAD: CDI, DM, optic atrophy, and deafness) AR with incomplete penetrance
Causes of NDI
Drugs
- Lithium
- Vaptans
- Orlistat
- Cisplatin
- tetracyclin Abx
Labs
- hyperCa
- HypoK
Sickle cell
Syndromes:
- Bartter
- Bardet Biedl
Genetics:
- AVPR2 mutation
- AQP2 mutation
Tests for DI
- Water dep
- Hypertonic Saline infusion
- Arginine copeptin stimulation test
Triple phase
- phases and duration, onset
DI (12h-few days)
onset day 1-2
- edema, cells “stunned”
- sometimes skip this phase
SIADH (up to 2 weeks)\
onset day 5-8
- ADH released as cells die
SI (indefinite)
onset variable, by day 14
how to test or DI in infants
○ No water deprivation
○ Administer DDAVP (1 µg SQ or IV over 20 min, max dose 0.4 µg/kg)
○ Measure urine osm at baseline and Q30min x2 hours
○ If urine osm doesn’t increase by >100 mosmol/kg over baseline, the diagnosis of nephrogenic DI is made and DNA should be obtained for mutation analysis
DI test: copeptin in water dep
- Ratio of stimulated copeptin (change in copeptin level over 8hrs during water dep) to plasma sodium (at the end of test)
≥0.02pmol/L = complete central DI
<0.02pmol/L = partial central DI
DI test: Plasma copeptin stimulated by hypertonic saline infusion
≤4.9 pmol/L = complete or partial central DI
>4.9 pmol/L = primary polydipsia
Advantages of using copeptin
- smaller sample volume
- copeptin assay does not require extraction step or other pre-analytical procedure
- copeptin is stable in plasma/serum ex vivo, handling is less complicated
how does hypertonic saline test work
administration of hypertonic saline to increase serum osmolality above 300 mOsm/kg, with subsequent measurement of serum vasopressin levels -> should see it rise
Copeptin helps differentiate what, how?
CDI:copeptin levels are low
primary polydipsia: intermediate
NDI: elevated
CDI tx
thirst intact
- DDAVP, titrate to effect
thirst not intact
- DDAVP
- fluid restrict to 1L/m2/d
Other than DDAVP, options to tx CDI
- High free water intake
- Low solute diet
- Thiazide diuretic
- Chlorpropamide
- Carbamazepine
- NSAID
Excess extracellular volume (edema, ascites) + urine w:
- low Na
- high Na
- low Na: hyperaldo
- high Na: SIADH
what is the post pit
not a gland but only the distal axon terminals of the hypothalamic magnocellular neurons that make up the neurohypophysis
what hormone problems decreased water excretion
Hypothyroidism and adrenal insufficiency
when present may mask diabetes insipidus
Atrial Natriuretic Peptide - what does it do
- where is it releases
- stimuli
Inhibits Aldosterone Secretion
Atria
increased volume,
increased Na,
neurologic inputs
where are the V2 receptors
collecting duct of kidneys
what will you see with DDAVP in water dec test with nephrogenic DI vs central DI
i. Nephrotic DI – urine osm <300 mOsm/kg and does not increase by >50% after DDAVP
ii. Complete central DI – urine osm increase by >50% after DDAVP
2 meds to tx NDI
HCTZ - causes natriuresis which produces some contraction of extracellular fluid volume, decrease GFR, decreased delivery of fluid to the collecting duct, and a decreased urine volume
ii. Indomethacin - has antidiuretic action that especially prolongs the action of vasopressin and administered DDAVP, it also decrease urine volume
