Physiology: ADH & Homeostasis

Question 1

Why can ADH and oxytocin pass through the liver without being metabolized?

Answer 1

The amide tail and cyclic ring protects the amino and carboxy terminals

Question 2

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?

Answer 2

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.

Question 3

5 mechanisms for regulating plasma osmolarity and blood volume

Answer 3

1) ADH 2) Thirst 3) RAAS 4) Natriuretic factor 5) Sodium appetite

Question 4

How does ADH allow for reabsorption of water in the nephron?

Answer 4

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

Question 5

What things are required to maintain water homeostasis?

Answer 5

1) Proper ADH secretion 2) Nephron that is sensitive to ADH 3) Hyperosmolar renal medulla to draw water back in 4) Normal thirst mechanism

Question 6

What does ADH do in hemorrhage

Answer 6

Secretes at such high levels that it becomes vasoactive

Question 7

Location of osmoreceptors

Answer 7

Supraoptic and paraventricular nuclei of anterior hypothalamus

Question 8

Location of volume receptors

Answer 8

Left atrium and pulmonary veins

Question 9

How does your body respond to the loss of H2O while you sleep at night?

Answer 9

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.

Question 10

Follow ADH and oxytocin as they move from the supraoptic and paraventricular nuclei in the hypothalamus to the blood

Answer 10

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.

Question 11

What type of drugs might a patient be taking if they are having difficulty retaining water?

Answer 11

Drugs that stimulate noradrenergic neurons. These inhibit ADH release.

Question 12

What type of drugs might a patient be taking if they are retaining too much water?

Answer 12

Drugs that stimulate cholinergic neurons. These stimulate ADH release.

Question 13

What types of injuries to the pituitary can cause permanent diabetes insipidus?

Answer 13

Damage to the hypothalamus, median eminance or upper stalk.

Question 14

What signs lead you to thinking about decreased ADH secretion?

Answer 14

Hypovolemia, hypertonic serum and hypernatremia.

Question 15

How do you treat someone with absent ADH secretion?

Answer 15

DDAVP (desamino D argenine vasopressin)

Question 16

Pathognomonic finding in nephrogenic diabetes insipidus

Answer 16

Inability of the distal nephron to react to ADH

Question 17

What urine value would you expect to see in someone with psychogenic polydipsia and polyuria? How do you treat them?

Answer 17

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.

Question 18

Assessing your differential for polyuria

Answer 18

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.

Question 19

Treatment for nephrogenic diabetes insipidus

Answer 19

Thiazide “diuretics” have a paradoxical action and allow for sodium and water reabsorption.

Question 20

Schwarz-Bartter syndrome

Answer 20

SIADH: 1) Excessive H2O retention 2) Dilutional hyponatremia 3) Inappropriately concentrated urine.

Question 21

4 causes of SIADH

Answer 21

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)

Question 22

What three things ultimately result in hyponatremia in patients with SIADH?

Answer 22

1) Increased GFR 2) Decreased renin (decreased aldosterone = decreased sodium retention) 3) Increased natriuretic factor (increases sodium excretion and decreases aldosterone release)

Question 23

What would you expect clinical signs to be like in someone with SIADH?

Answer 23

Inappropriately concentrated urine for how much extra volume they are carrying. Detectable serum ADH. Serum hypoosmolality.

Question 24

Major symptoms associated with SIADH?

Answer 24

Headaches, drowsiness, weakness, stupor, come and seizure. It gets worse as hyponatremia progresses.

Question 25

When would ethanol be useful in diagnosing SIADH?

Answer 25

If the cause resides in the hypothalamus, ethanol will suppress ADH secretion.

Question 26

Treating SIADH

Answer 26

1) Remove cause 2) Curtain water intake 3) Suppress ADH (ethanol or dilantin) 4) Inhibit ADH at nephron (lithium)

Question 27

Clinical circumstances that may lead to SIADH?

Answer 27

Heart failure, liver cirrhosis, renal failure and adrenal failure

Question 28

Neuroendocrine reflexes caused by oxytocin

Answer 28

Lactation and parturition

Question 29

Most common cause of pituitary necrosis

Answer 29

Sheehan’s syndrome: circulatory collapse secondary to hemorrhage at parturition causes ischemia in the enlarge pituitary.

Question 30

Three types of pituitary tumors

Answer 30

Chromophobe (60-70%), acidophilic (30%) and basophilic (rare)

Question 31

MEN1

Answer 31

Multiple endocrine neoplasia: pituitary, parathyroid and pancreas

Question 32

MEN2

Answer 32

Multiple endocrine neoplasia: thyroid, parathyroid and adrenal

Question 33

Most frequent symptoms of pituitary adenomas

Answer 33

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

Question 34

How do we treat a prolactinoma?

Answer 34

Dopamine, it is the natural inhibitor of prolactin release.