Role of ADH & Disorders of ADH Secretion Flashcards
What are the functions of ADH, both at normal and high concentrations
At rest, ADH acts on receptors on the distal convoluted tubule and collecting duct and increases water reabsorption. At higher concentrations is causes vasoconstriction (hence the name vasopressin)
How is ADH secretion regulated
- Osmoreceptors located in the supraoptic and paraventricular nuclei of the anterior hypothalamus (sensitive to osmolarity of ECF)
- Volume receptors located in the left atrium and pulmonary veins
Name the 5 ways we regulate plasma osmolarity and blood volume
- ADH (controls free H2O clearance by the kidney)
- Thirst
- Renin-Angiotensin-Aldosterone System (principal salt regulating system)
- Natriuretic Factor (promotes saline diruresis, i.e., NaCl excretion)
- Central Sodium Appetite
Describe how ADH goes from precursor protein to real life ADH
- Precursor protein is made in the supraoptic or paraventricular nucleus of the anterior hypothalamus. The proteins travel down the axon in Golgi secretory granules.
- During their travels, the protein gets chopped up, making ADH (or oxytocin) and a 10000Da protein called neurophysin
- ADH stored in nerve terminal (aka Herring body)
- Both the hormone and neurophysin are released upon depolarization of neuron
What is the fate of circulating ADH
- Continues to circulate (15 min half life)
- Inactivated by proteolytic enzymes
- Peed out
What does oxytocin do?
- Promote uterine myometrium contractions when baby’s coming out
- Stimulate contractions of myoepithelial cells in breast, releasing milk to baby
Neurohypophyseal Diabetes Insipidus (DI)
No ADH secretion, leading to incredible amounts of pee (and hypovolemia, hyponatremia, hyperosmolality). Compensation with lots of H2O drinking can help but treat extreme cases with Desmopressin (DDVAP), a super active ADH analog
Nephrogenic Diabetes Insipidus
Kidney can not respond to ADH signal. Can be congenital problem with receptor or some other part of second messenger pathway OR from hypercalcemia, hypokalemia, obstructive uropathy, sickle cell disease, chronic lithium administration. This presents as Neurohypophyseal DI, but is not corrected with DDVAP
Psychogenic polydipsia: “compulsive water drinking”
Can’t quench dat thirst cause you crazy. Serum hypoosmolality suppresses ADH secretion. Without ADH, renal water conservation doesn’t occur and large but appropriate quantities of pee bring serum osmolality back towards normal. Big note here is that you CAN produce ADH, but its production is suppressed by hypoosmolality of ECF.
Ddx of Neurohypophyseal DI, nephrogenic DI and psychogenic polydipsia. How will you tell them apart!
- Restrict water. Should increase ADH release. If response is increased urine concentration and decreased urine volume, then ADH response is normal and Dx is psychogenic polydipsia.
- If #1 is abnormal, give ADH analog. If get normal urine response, problem is neurohypophyseal DI.
- If #2 is abnormal, its nephrogenic DI.
4 Causes of “Inappropriate Release of ADH”
- Disruption of hypothalamus causing change in ADH set point. ADH released in face of inhibitory stimuli.
- Faulty volume receptor. For example in right sided heart failure, less volume detected by left atrium despite no true hypovolemia.
- ADH secreted by tissue other than posterior pituitary (tumor)
- Certain drugs enhance ADH action on nephron (some chemo drugs)
Hallmark of the “Inappropriate ADH syndrome”
Serum hypoosmolality
Soooo what happens when we have a shit load of ADH like in “Inappropriate ADH syndrome?
- Hyperosmolar urine despite hypoosmolality of serum because you got so much ADH thats pulling in water from the nephron.
- Increased glomerular filtration rate
- Decreased renin–>decreased aldosterone–>decreased salt (and thus water) reabsorption into the nephron
- Stretched atrium from increased blood volume causes release of atrial natriuretic hormone, which further inhibits aldosterone release from adrenal cortex and decrease salt reabsorption in nephron.
- End result: increased salt (and H2O) wasting in light of dilutional hyponatremia
What’s a common condition that leads to pituitary infarction (think pregger lady)
Sheehan’s syndrome: results from hemorrhage secondary to parturition (having a baby). While preggers, the mom’s pituitary undergoes hyperplasia (remember what hormone is responsible for that?..estrogen) and can outgrow its blood supply. Excessive bleeding during birth can shunt away blood from the pituitary causing infarction (mostly to the anterior lobe)
What’s another vascular disease that can upset the pituitary (guess my thought…sorry)
Carotid artery aneurysms , or those arising from the suprasellar area from the circle of Willis, can compress the axis, or enlarge and grow into the sella turcica.
