Posterior Pituitary, hypo and hyper-Na (DJ)

Question 1

Conditions assc with water retention are often accompanied by inc expression of

Answer 1

AQP2

Question 2

What does ADH do (biochem and effects) in the kidneys?

Answer 2

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)

Question 3

What ADH receptors mediate CV effects (smooth muscle contraction = vasoconstriction to ↑BP)

Answer 3

V(1A)

Question 4

What ADH receptors mediate renal effects

Answer 4

V(2)

Question 5

What ADH receptors mediate ACTH release

Answer 5

V(1B)

receptors found in ant pit and median eminence

Question 6

Time of day: Max ADH secretion _____ with min _____

Answer 6

Max ADH secretion late at night and early in morning

min in early afternoon

Question 7

ADH maintains Posm at

Answer 7

~280-296 mOsm/kg

Question 8

What are the mechs that control ADH release?

Answer 8

1. ↑ plasma omolarity
2. ↓ PV sensed by stretch receptors in LA and pulm veins
3. Activation of carotid and aortic baroreceptors in response to hypotension
4. Cholinergic/sympathetic and Beta-adrenergic stimulation causes ADH release
5. Secrete more ADH as we get older (Age)
6. Drugs
7. ↑ cortisol → Posm must get to a higher conc to get ADH release → inc water loss in urine

**SODAS BC

Question 9

This also stimulates thirst (via Ang II) → ADH release

Answer 9

↑ plasma omolarity

Question 10

sensed by stretch receptors in LA and pulm veins

Answer 10

↓ PV

Question 11

When >10% loss in fluid volume, ____ overcomes osmolarity regulation

Answer 11

↓ PV response (inducing release of ADH)

Question 12

Inability to concentrate urine due to inability to secrete ADH →

Answer 12

polyuria

Question 13

How do pts with ADH deficiency maintain H2O balance?

Answer 13

Rely on intact thirst mechanism to maintain water balance

Question 14

What are the acquired causes of ADH deficiency?

Answer 14

• Idiopathic (30% have AVP Abs)
• Tumors of brain
• Head trauma
• Granulomatous dz involving hypothalamic-pituitary area
• CNS infection
• Cerebral vascular dz

Question 15

Clinical presentation of ADH deficiency

Answer 15

Polyuria, excessive thirst (polydipsia), nocturia

Question 16

effect of anterior pituitary insufficiency on ADH

Answer 16

Adrenal insufficiency → ↓cortisol → ↑ADH release (lower threshold) → cannot dilute urine

Question 17

Insufficient ADH

Answer 17

Neurogenic DI

Question 18

complete or partial resistance to ADH

Answer 18

nephrogenic DI

Question 19

Habitual fluid drinking

Answer 19

Primary polydipsia

Question 20

abnormal thirst mech that causes habitual fluid drinking

Answer 20

dispogenic DI

Question 21

Causes of nephrogenic DI

Answer 21

idiopathic
familial X-linked dz
mutation in V2 receptor gene
injuries to kidney (toxic or metabolic)

Question 22

clinical defn of polyuria

Answer 22

urine volume > 2.5 liters/24 hrs

Question 23

How are the different types of DI distinguished?

Answer 23

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

Question 24

Conditions assc with excess ADH secretion

Answer 24

SIADH, CHF, cirrhosis

Question 25

Etiology of SIADH with example

Answer 25

Malignant tumors with autonomous AVP release (small cell carcinomas of the lung)

Non-malignant pulmonary diseases (TB and pneumonia)

CNS disorders (meningitis)

Drugs (narcotics)

Question 26

How does non-malignant pulm dz stimulate ADH release?

Answer 26

Autonomously secretes ADH or reduces LA filling pressure which stimulates ADH release

Question 27

Excessive ADH + normal water intake →

Answer 27

water retention, hyponatremia, extra and intracellular hypotonicity

Question 28

In SIADH, what causes Na loss

Answer 28

(1) inc glomerular filtration rate (2) dec aldosterone secretion (3) ANP released due to volume expansion

Question 29

Na loss in SIADH prevents…and causes…

Answer 29

development of edema and HTN

causes euvolemic hyonatremia

Question 30

Clinical presentation of SIADH

Answer 30

Confusion → convulsions → coma

Low Sr Na < 130 meq
Urine Na > 20 meq (=Na wasting)

Question 31

How is SIADH diagnosed?

Answer 31

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)

Question 32

aka sickle cell syndrome or essential hyponatremia

Answer 32

Malignancy or condition that causes the osmoreceptors to reset such that ADH is released at lower Posm

Question 33

How is SIADH managed/treated?

Answer 33

1. treat underlying disorder and if persists…
   - water restriction
   - meds that block ADH action of DCT
   - carefully correct hyponatremia
   - vaptans

Question 34

V2 receptor antagonists

Answer 34

vaptans

Question 35

selective V1a-receptor antagonist

Answer 35

Reclovaptan

Question 36

Meds that block effects of ADH on DCT

Answer 36

demeclocycline

lithium

Question 37

Sever water intoxication has been reported with high doses and simultaneous admin of hypotonic fluids

Answer 37

oxytocin

Question 38

oxytocin is may play a role in what dz/conditions

Answer 38

autism and schizophrenia

*Assc with learning, anxiety, social memory, attachment, sexual and maternal behavior, human bonding and trust