Posterior pituitary- hyper and hyponatremia

Question 1

Structure of OT and ADH

Answer 1

nonpeptide, ring structure with a disulfide bond

Question 2

Where are OT and ADH synthesized?

Answer 2

SON and PVN of hypothalamus

Question 3

Describe synthesis of OT and ADH

Answer 3

Macromolecular precursors that are cleaved to yield hormone, neurphysin, and other peptides

Question 4

How are OT and ADH secreted?

Answer 4

stored in vesicles at terminals, secreted by Ca dependent exocytosis

Question 5

3 receptor subtypes that mediate action of ADH

Answer 5

VA1, VA1, VB

Question 6

What are the stimulatory solutes that play a role in osmotic regulation of ADH?

Answer 6

Sodium, mannitol, urea

Question 7

Does glucose stimulate release of ADH

Answer 7

no

Question 8

What does N/V, emotional stress, and pain do to ADH release?

Answer 8

Stimulate ADH release

Question 9

What happens to ADH release with aging?

Answer 9

Increase

Question 10

What does ethanol do to ADH release?

Answer 10

inhibits

Question 11

How does cortisol act concerning ADH activity?

Answer 11

They have antagonist effect on each other. Cortisol elevates the osmotic threshold for AVP release and increase solute free water excretion

Question 12

Can RAS stimulate ADH secretion?

Answer 12

yes

Question 13

Cellular MOA of ADH on renal tubular cells

Answer 13

V2 receptors- activate adenylyl cyclase to increase cAMP and enhance water permeability

Question 14

Cellular MOA of ADH on vascular smooth muscle

Answer 14

V1- stimulates influx of Ca ions and vasoconstriction

Question 15

Describe the role AQP2 with ADH

Answer 15

AQP2 is localized to the principal cells of the connecting tubule and collecting duct and is the major mediator of ADH activity in the kidney. It is the predominant ADH regulated water channel.

Question 16

Lack of AQP2 causes what?

Answer 16

congenital or primary forms of diabetes insipidus

Question 17

Over-expression of AQP2 causes what?

Answer 17

water retention and can be associated with SIADH, congestive heart failure, and pregnancy

Question 18

Structure of AQP

Answer 18

6 transmembrane a-helices and N and C terminus on cytoplasm side. There are 5 inter-helical loop regions.

Question 19

How does ADH acutely regulate permeability of distal collecting duct?

Answer 19

trafficking AQP2 from intracellular vesicles to apical membrane

Question 20

_____ is a disorder defined by failure to concentrate urine as a result of decreased secretion of osmoregulated ADH.

Answer 20

Neurogenic/central DI

Question 21

Clinical presentation of central DI

Answer 21

Polyuria day and night, thirst and polydipsia with preference for ice-cold water
Children: enuresis

Question 22

Causes of central DI

Answer 22

Most are aqcuired: idiopathic, tumors, trauma, granulomatous disease, infection, cerebral vascular disorders
Can be familial

Question 23

3 pathogenic mechanisms of polyuria

Answer 23

1. Neurogenic DI
2. Nephrogenic DI
3. Primary polydipsia: psychogenic DI or dipsogenic DI

Question 24

What will plasma and urine osmolarity look like with polyuria?

Answer 24

Neurogenic and nephrogenic DI- Plasma: high
Urine: low
Primary polydipsia: both will be low

Question 25

How can you tell the difference between neurogenic, nephrogenic DI, and primary polydipsia?

Answer 25

ADH:Neuro will respond to ADH. Nephro will not. Primary polydipsia will respond.
Water deprivation: Neuro: plasma osmolality goes up, urine remains dilute (should be concentrating!) Nephro: Fail to respond. Primary: respond.

Question 26

What clinical conditions are associated with elevated ADH?

Answer 26

CHF, cirrhosis, SIADH

Question 27

What does SIADH do when there is normal water intake?

Answer 27

Cause hypo-osmolality and hyponatremia

Question 28

Pathogenic mechanisms of SIADH

Answer 28

1. Malignant tumors- lung carcinoma (80% due to SCC)
2. nonmalignant pulm diseases. this type of hyponatremia is common in TB and pneumonia
3. CNS disorders- release of ADH due to inflammation or lesion.
4. Drugs

Question 29

Why is there no edema in SIADH? (Euvolemic hyponatremia)

Answer 29

Na secretion is enhanced due to GFR and ANH. This prevents edema and HTN

Question 30

Clinical and lab features of SIADH

Answer 30

Present with weight gain, weakness, lethargy, confusion–> convulsions and coma.
Labs: low levels of everything in serum
Urine: inappropriately concentrated with Na.

Question 31

DDx with SIADH

Answer 31

1. Hypovolemic hyponatremia: adrenal insufficiency, diarrhea, diuretic therapy, nephropathy
2. Hypervolemic hyponatremia: edema
3. Pseudohyponatremia: severe hyper-lipids, proteins, glucose.
4. Sickle cell syndrome or essential hyponatremia: chronic bad disease resets osmorereceptors to a low level- ADH is secreted at lower osmolarity than it should be.

Question 32

What is the consequence of biochemical similarity between ADH and OT?

Answer 32

OT as pharmacological doses can alter water regulation at kidney- water intoxication

Question 33

What kind of behaviors has OT been associated with?

Answer 33

Non social: learning, anxiety, feeding, pain

Social: social memary, attachment, sexual behavior, bonding/trust, aggression

Question 34

What social disorders has OT been associated with?

Answer 34

Autism and schizophrenia

Question 35

Acute presentation of hyponatremia

Answer 35

Early: nausea, vomiting, headach
Late: seizure coma resp. arrest

Question 36

Chronic presentation of hyponatremia

Answer 36

lethargy, confusion, cramps, neuro impairment

Question 37

What does nicotine do to ADH secretion?

Answer 37

increase

Question 38

Tx of SIADH

Answer 38

Remove underlying cause, fluid restriction, block renal tubular response, (hypertonic saline if you’re feeling on the edge)

Question 39

What are vaptans?

Answer 39

ADH V2 antagonists

Question 40

Why do you have to be careful in giving hypertonic saline to someone with SAIDH?

Answer 40

Risk of osmotic demyelination syndrome