Posterior Pituitary, hypo and hyper-Na (DJ) Flashcards
Conditions assc with water retention are often accompanied by inc expression of
AQP2
What does ADH do (biochem and effects) in the kidneys?
upregulates translocation of AQP2 from intracellular vesicles to the apical PM of collecting duct
→↑permeability of H2O in the DCT and CD to increase H2O reabsorption)
What ADH receptors mediate CV effects (smooth muscle contraction = vasoconstriction to ↑BP)
V(1A)
What ADH receptors mediate renal effects
V(2)
What ADH receptors mediate ACTH release
V(1B)
receptors found in ant pit and median eminence
Time of day: Max ADH secretion _____ with min _____
Max ADH secretion late at night and early in morning
min in early afternoon
ADH maintains Posm at
~280-296 mOsm/kg
What are the mechs that control ADH release?
- ↑ plasma omolarity
- ↓ PV sensed by stretch receptors in LA and pulm veins
- Activation of carotid and aortic baroreceptors in response to hypotension
- Cholinergic/sympathetic and Beta-adrenergic stimulation causes ADH release
- Secrete more ADH as we get older (Age)
- Drugs
- ↑ cortisol → Posm must get to a higher conc to get ADH release → inc water loss in urine
**SODAS BC
This also stimulates thirst (via Ang II) → ADH release
↑ plasma omolarity
sensed by stretch receptors in LA and pulm veins
↓ PV
When >10% loss in fluid volume, ____ overcomes osmolarity regulation
↓ PV response (inducing release of ADH)
Inability to concentrate urine due to inability to secrete ADH →
polyuria
How do pts with ADH deficiency maintain H2O balance?
Rely on intact thirst mechanism to maintain water balance
What are the acquired causes of ADH deficiency?
- Idiopathic (30% have AVP Abs)
- Tumors of brain
- Head trauma
- Granulomatous dz involving hypothalamic-pituitary area
- CNS infection
- Cerebral vascular dz
Clinical presentation of ADH deficiency
Polyuria, excessive thirst (polydipsia), nocturia
effect of anterior pituitary insufficiency on ADH
Adrenal insufficiency → ↓cortisol → ↑ADH release (lower threshold) → cannot dilute urine
Insufficient ADH
Neurogenic DI
complete or partial resistance to ADH
nephrogenic DI
Habitual fluid drinking
Primary polydipsia
abnormal thirst mech that causes habitual fluid drinking
dispogenic DI
Causes of nephrogenic DI
idiopathic
familial X-linked dz
mutation in V2 receptor gene
injuries to kidney (toxic or metabolic)
clinical defn of polyuria
urine volume > 2.5 liters/24 hrs
How are the different types of DI distinguished?
After dehydration + exogenous ADH
- neurogenic: will respond and be able to conc urine
- nephrogenic: will not respond; urine will still be dilute
- primary polydipsia: dehydration alone will cause urine to conc (its just an intake problem); but note, it will not respond to ADH bc body would have already made and saturated ADH receptors during dehyration prd
Administer hypertonic saline:
neurogenic: no ↑ plasma ADH
nephrogenic: ↑plasma ADH
primary polydipsia: ↑plasma ADH
Conditions assc with excess ADH secretion
SIADH, CHF, cirrhosis
Etiology of SIADH with example
Malignant tumors with autonomous AVP release (small cell carcinomas of the lung)
Non-malignant pulmonary diseases (TB and pneumonia)
CNS disorders (meningitis)
Drugs (narcotics)
How does non-malignant pulm dz stimulate ADH release?
Autonomously secretes ADH or reduces LA filling pressure which stimulates ADH release
Excessive ADH + normal water intake →
water retention, hyponatremia, extra and intracellular hypotonicity
In SIADH, what causes Na loss
(1) inc glomerular filtration rate (2) dec aldosterone secretion (3) ANP released due to volume expansion
Na loss in SIADH prevents…and causes…
development of edema and HTN
causes euvolemic hyonatremia
Clinical presentation of SIADH
Confusion → convulsions → coma
Low Sr Na < 130 meq
Urine Na > 20 meq (=Na wasting)
How is SIADH diagnosed?
exclusion:
- volume status to determine if euvolemic
- pseudohyponatremia due to severe hyperlipidemia, hyperproteinuria, or hyperglycemia
- Malignancy or condition that causes the osmoreceptors to reset such that ADH is released at lower Posm (aka sickle cell syndrome or essential hyponatremia)
aka sickle cell syndrome or essential hyponatremia
Malignancy or condition that causes the osmoreceptors to reset such that ADH is released at lower Posm
How is SIADH managed/treated?
- treat underlying disorder and if persists…
- water restriction
- meds that block ADH action of DCT
- carefully correct hyponatremia
- vaptans
V2 receptor antagonists
vaptans
selective V1a-receptor antagonist
Reclovaptan
Meds that block effects of ADH on DCT
demeclocycline
lithium
Sever water intoxication has been reported with high doses and simultaneous admin of hypotonic fluids
oxytocin
oxytocin is may play a role in what dz/conditions
autism and schizophrenia
*Assc with learning, anxiety, social memory, attachment, sexual and maternal behavior, human bonding and trust
