What hormones are STORED and RELEASED by the Posterior Pituitary (2 total)
Vasopressin (Arginine vasopressin = AVP = ADH)
Oxytocin
Where in the Hypothalamus are Oxytocin and ADH produced?
Supra-Optic nuclei (oxytocin)
Paraventricular nuclei (ADH)
Function of Oxytocin
Uterine contraction
Milk letdown (Contraction of mammary smooth muscles)
Function of ADH (Vasopressin)
- Antidiuretic FX
- H2O retention by stimulating H2O movement across renal tubular cell membranes
- V2 - Vasopressor FX
- Increase ACTH by augmenting ACTH response to CRH
- V1 & V3
The (V1/V2/V3) ADH receptor stimulates vasoconstriction and vWF release
V1
The (V1/V2/V3) ADH receptor has antidiuretic activity
V2
The (V1/V2/V3) ADH receptor stimulates ACTH secretion from the pituitary
V3
Oxytocin and ADH act via what kind of receptor
G-protein coupled receptors
What are some triggers for ADH release
Dehydration
Blood loss
Nausea
(Hypertension/Hypotension) triggers ADH release
Hypotension (need to reabsorb water to improve blood pressure)
(Osmo/baro)receptors are much more sensitive for the release of ADH
Osmoreceptors (osmolality is most effective regulator of plasma AVP)
Excess urinary loss of water due to deficiency or insensitivity to ADH (vasopressin)
Diabetes Insipidus (DI)
- Central
- Nephrogenic
Possible causes of Polyuria (at least 3 liters of urine per day)
- Primary polydipsia (excessive water intake with normal pit. fx)
- Central DI
- Nephrogenic DI
How to help diagnose Diabetes Insipidus
Water Deprivation test
- Administer desmopressin (DDAVP) and withhold water intake
- Assess urine osmolality
Treatment for Central Diabetes Insipidus
Desmopressin (DDAVP)
Synthetic AVP
Chlorpropamide
Why might Desmopressin be the best tx for those with Central DI + CAD
Selective for V2 (so no effect on V1 or vascular smooth muscle)
An inappropriate retention of water due to excess ADH; characterized by hyponatremia, high urine osmolality (urine Na+ >20), euvolemia (normal BP), and urine osmolality > plasma osmolality
SIADH (Syndrome of Inappropriate ADH)
*hypotonic hyponatremia
4 main causes of SIADH
- CNS disease/neoplasm (meningitis, abscess)
- Pulmonary disease (TB, pneumonia)
- Pulmonary neoplasm (small cell carcinoma, squamous cell carcinoma)
- Drugs (chlorpropamide, narcotics)
Treatment for SIADH
Asymptomatic: fluid RESTRICTION (cheap and safest)
Symptomatic: HYPERTONIC SALINE
Examples of Vasopressin antagonists (expensive and only used short term to treat SIADH)
Conivaptan
Tolvaptan
*-vaptan ending
The pathway from the hypothalamus to the posterior pituitary is called
hypothalamic-neurohypophyseal system
The pathway from the hypothalamus to the anterior pituitary is called
hypothalamic-hypophyseal system
Precursor of vasopressin
propressophysin
Precursor of oxytocin
Prooxyphysin
propressophysin must be cleaved to form vasopressin + _________, which is noncovalently bonded to vasopressin.
neurophysin (different from oxytocin’s)
Prooxyphysin must be cleaved to form oxytocin + _________, which is noncovalently bonded to vasopressin.
neurophysin (different from vasopressin’s)
What are some triggers for oxytocin release
- Uterine/vaginal distention
2. Tactile stimulation from nipple suckling
Patients with polydipsia (excessive thirst), polyuria, and nocturia indicate
AVP deficiency, insufficiency, or insensitivity
- diabetes insipidus
What can cause primary polydipsia?
- drugs that cause dry mouth
- Psychiatric illness
- Hypothalami damage in the thirst center
What electrolyte conditions can cause nephrogenic DI?
Hypercalcemia
Hypokalemia
What drugs can cause nephrogenic DI?
lithium
amphotericin B
gentamicin
cisplatin
Describe urine volume, urine osmolality, and serum Na+/osmolality of central DI
Urine volume: inc.
Urine osmolality: dec.
Serum Na+/Osmolality: inc.
Describe urine volume, urine osmolality, and serum Na+/osmolality of Nephrogenic DI
Urine volume: inc.
Urine osmolality: dec.
Serum Na+/Osmolality: inc.
Describe urine volume, urine osmolality, and serum Na+/osmolality of Primary polydipsia
Urine volume: inc.
Urine osmolality: dec.
Serum Na+/Osmolality: normal or dec.
Urine osmolality will _____ in CDI after water deprivation and DDAVP administration
increase
Low plasma osmolality with appropriately low plasma AVP describes what condition?
Primary polydipsia
Abnormally high AVP regardless of serum osmolality
Nephrogenic DI
Abnormally low AVP even with high serum osmolality
Central DI
What tx might be the best option for partial vasopressin deficiency?
Chlorpropamide
*b/c it potentiates the effects of endogenous vasopressin
Treatment for Nephrogenic Diabetes Insipidus
HCTZ
Amiloride
What is the antidote for lithium-induced nephrogenic DI b/c of it blunts lithium uptake in the DCT and CD.
Amiloride
Formula to figure out how much water needs to be replaced as an ACUTE DI tx
Water Deficit = 0.6 x weight (in kg) x [(serum Na+/140)-1]
Symptoms of SIAD/SIADH
HA, confusion, nausea, personality changes
What must NOT be given to treat SIADH
ISOTONIC SALINE
Swelling of myelin sheaths around CNS nerves that can lead to necrosis and irreversible neurologic damage; occurs when hyponatremia is corrected too quickly via hypertonic saline (> 12 mEq/L in 24 hous); symptoms include LETHARGY, ATAIXA, and MUTISM (unable to speak); can lead to COMA and DEATH!!
Osmotic Demyelination Syndrome (ODS)
AKA. Central Pontine Myelinolysis