Posterior Pituitary

Question 1

Explain the mechanism of ADH:

Answer 1

ADH binds to G-protein coupled receptor on the cell surface of the collecting tubule

Leads to Activation of adenylate cyclase → ↑ cAMP → PKA

PKA phosphorylates aquaporin 2 (water channel) → ↑ membrane permeability to water and decreased excretion of free water

Question 2

Where are osmoreceptors located and what activates it?

Answer 2

Anterior hypothalamus

increase of only 2-3 mOsm/kg

Question 3

What are causes of nephrogenic DI>

Answer 3

Congenital (mutation of vasopressin receptor (V2) or mutation of the aquaporin gene) (very rare)

Chronic kidney diseases, urinary tract obstruction

Drugs: Lithium (reduced aquaporin channel, inhibits cAMP formation in collecting tubule), anti-viral, anti-neoplastic

Electrolyte disturbance: Hypercalcemia (downregulation of water channel in the medulla, tubulointerstitial damage from calcium deposit), chronic hypokalemia

Question 4

What are classic signs of DI?

Answer 4

Elevated serum sodium and serum osmolality with low urine osmolality (dilute urine)

Question 5

How do you differentiate DI vs primary polydipsia?

Answer 5

Water Deprivation Test:
Patients come in Water deprived for 4-8 hours
and urine osmolarity measured hourly; ADH administered later on

Central DI
Uosm remains low after 8h but ↑ with vasopressin (DDAVP)

Nephrogenic DI
Uosm remains low after 8h and no increase with DDAVP

Primary polydipsia
Uosm ↑ after 8 h of dehydration (>800 mOsm/l, urine output < 30 cc/hour)

Question 6

SIADH stands for?

Answer 6

Syndrome of Innaporpriate ADH

Question 7

What is the diagnostic criteria for SIADH?

Answer 7

• Euvolemic hyponatremia with low serum osmolality
• Inappropriately high urine osmolality (if serum osmolality is low, the body should be trying to excrete free water )
• Normal adrenal, thyroid and renal function
  Both cortisol and thyroid hormone are required to excrete free water and in chronic kidney disease, kidney loses the ability to concentrate urine
• Absence of interfering medications (eg. diuretics)

Question 8

What are causes of SIADH?

Answer 8

CNS Disease
- Stroke, hemorrhage, infection, trauma, neoplasm
Pulmonary disease
- Infection: Pneumonia, TB, lung abscess
- Neoplasm
Surgery, including anesthesia
Cancer (ectopic production of ADH)
- Lung (small cell), pancreas, brain, small intestine
Pain
Drugs: Opioids, anti-convulsants (carbamazepine, valproic acid), cyclophosphamide, old oral hypoglycemics, TCAs (amitriptyline), some chemotherapy (vincristine)
Post-pituitary surgery: Transient release of uncontrolled ADH

Question 9

List the treatment for SIADH:

Answer 9

Hypertonic saline (3%) 
- Have to give a fluid that is more concentrated than their urine, otherwise will worsen hyponatremia

Demeclocycline or lithium in chronic cases
- Both cause nephrogenic DI (ie. impair responsiveness of the kidneys to the ADH)

Vasopressin antagonist

Question 10

List the actions of oxytocin in various groups:

Answer 10

Uterine Myometrium
- Parturition
Clamping ruptured blood vessels to prevent excessive bleeding
Restoration of uterine size via uterine contraction

• Mammary myometrium
  Milk let-down, promoting movement of milk into the breast
• Men
  Role in sperm motility

- Social Behavior
Mother-infant bonding
Trust
Anxiety
Sexual arousal