Physiology: ADH & Homeostasis Flashcards
Why can ADH and oxytocin pass through the liver without being metabolized?
The amide tail and cyclic ring protects the amino and carboxy terminals
A patient comes to the ED after suffering severe trauma in a car accident. MRI shows a severed infundibulum. How would you expect this patient’s fluid homeostasis to change?
Loss of infundibulum = loss of release of ADH. Loss of ADH = decreased fluid retention. The patient will go from losing about 1L of water in the urine per day to 15-20L per day if not treated.
5 mechanisms for regulating plasma osmolarity and blood volume
1) ADH 2) Thirst 3) RAAS 4) Natriuretic factor 5) Sodium appetite
How does ADH allow for reabsorption of water in the nephron?
ADH binds to cell surface receptors in the distal tubule and collecting duct. This activates adenylate cyclase, increases levels of cAMP and the nephron’s permeability to water increases
What things are required to maintain water homeostasis?
1) Proper ADH secretion 2) Nephron that is sensitive to ADH 3) Hyperosmolar renal medulla to draw water back in 4) Normal thirst mechanism
What does ADH do in hemorrhage
Secretes at such high levels that it becomes vasoactive
Location of osmoreceptors
Supraoptic and paraventricular nuclei of anterior hypothalamus
Location of volume receptors
Left atrium and pulmonary veins
How does your body respond to the loss of H2O while you sleep at night?
Osmoreceptors sense increases serum tonicity and volume receptors sense decreased volume. This stimulates increased ADH release and H2O reabsorption. Thirst is also stimulated when you wake up and increases H2O intake. This dilutes the blood and increases blood volume resulting in a decrease in ADH and thirst.
Follow ADH and oxytocin as they move from the supraoptic and paraventricular nuclei in the hypothalamus to the blood
They are cleaved in and transported down the axons and stored in the pars nervosa as Herring bodies. On depolarization they are released as hormone and neurophysin. Enzymes in the blood, liver and kidney degrade ADH in about 15 minutes and it is excreted through the urine.
What type of drugs might a patient be taking if they are having difficulty retaining water?
Drugs that stimulate noradrenergic neurons. These inhibit ADH release.
What type of drugs might a patient be taking if they are retaining too much water?
Drugs that stimulate cholinergic neurons. These stimulate ADH release.
What types of injuries to the pituitary can cause permanent diabetes insipidus?
Damage to the hypothalamus, median eminance or upper stalk.
What signs lead you to thinking about decreased ADH secretion?
Hypovolemia, hypertonic serum and hypernatremia.
How do you treat someone with absent ADH secretion?
DDAVP (desamino D argenine vasopressin)
Pathognomonic finding in nephrogenic diabetes insipidus
Inability of the distal nephron to react to ADH
What urine value would you expect to see in someone with psychogenic polydipsia and polyuria? How do you treat them?
Increased fluid uptake causes hypoosmotic serum. This suppresses ADH and urine will be hypoosmotic. Water restriction will allow release of the excess water, serum osmolality increases and ADH secretion resumes.
Assessing your differential for polyuria
1) Water restriction: if they respond then it’s psychogenic. 2) DDAVP: if they respond then its neurohypophyseal 3) If they don’t respond it’s nephrogenic.
Treatment for nephrogenic diabetes insipidus
Thiazide “diuretics” have a paradoxical action and allow for sodium and water reabsorption.
Schwarz-Bartter syndrome
SIADH: 1) Excessive H2O retention 2) Dilutional hyponatremia 3) Inappropriately concentrated urine.
4 causes of SIADH
1) Change in hypothalamic set point 2) Faulty stimuli (right-sided heart failure or liver cirrhosis give trick atrial volume receptors) 3) Ectopic ADH secretion (brochogenic carcinoma or Tb) 4) Drugs (chemotherapy enhances ADH effect at nephron)
What three things ultimately result in hyponatremia in patients with SIADH?
1) Increased GFR 2) Decreased renin (decreased aldosterone = decreased sodium retention) 3) Increased natriuretic factor (increases sodium excretion and decreases aldosterone release)
What would you expect clinical signs to be like in someone with SIADH?
Inappropriately concentrated urine for how much extra volume they are carrying. Detectable serum ADH. Serum hypoosmolality.
Major symptoms associated with SIADH?
Headaches, drowsiness, weakness, stupor, come and seizure. It gets worse as hyponatremia progresses.
When would ethanol be useful in diagnosing SIADH?
If the cause resides in the hypothalamus, ethanol will suppress ADH secretion.
Treating SIADH
1) Remove cause 2) Curtain water intake 3) Suppress ADH (ethanol or dilantin) 4) Inhibit ADH at nephron (lithium)
Clinical circumstances that may lead to SIADH?
Heart failure, liver cirrhosis, renal failure and adrenal failure
Neuroendocrine reflexes caused by oxytocin
Lactation and parturition
Most common cause of pituitary necrosis
Sheehan’s syndrome: circulatory collapse secondary to hemorrhage at parturition causes ischemia in the enlarge pituitary.
Three types of pituitary tumors
Chromophobe (60-70%), acidophilic (30%) and basophilic (rare)
MEN1
Multiple endocrine neoplasia: pituitary, parathyroid and pancreas
MEN2
Multiple endocrine neoplasia: thyroid, parathyroid and adrenal
Most frequent symptoms of pituitary adenomas
1) Loss of vision 2) Headache 3) Abnormal hormone secretion (GH w/ acromegaly and gigantism and PRL w/ galactorrhea and amenorrhea most common, sometimes ACTH w/ Cushing’s) 4) Loss of pituitary function
How do we treat a prolactinoma?
Dopamine, it is the natural inhibitor of prolactin release.
