Posterior pituitary- hyper and hyponatremia Flashcards
Structure of OT and ADH
nonpeptide, ring structure with a disulfide bond
Where are OT and ADH synthesized?
SON and PVN of hypothalamus
Describe synthesis of OT and ADH
Macromolecular precursors that are cleaved to yield hormone, neurphysin, and other peptides
How are OT and ADH secreted?
stored in vesicles at terminals, secreted by Ca dependent exocytosis
3 receptor subtypes that mediate action of ADH
VA1, VA1, VB
What are the stimulatory solutes that play a role in osmotic regulation of ADH?
Sodium, mannitol, urea
Does glucose stimulate release of ADH
no
What does N/V, emotional stress, and pain do to ADH release?
Stimulate ADH release
What happens to ADH release with aging?
Increase
What does ethanol do to ADH release?
inhibits
How does cortisol act concerning ADH activity?
They have antagonist effect on each other. Cortisol elevates the osmotic threshold for AVP release and increase solute free water excretion
Can RAS stimulate ADH secretion?
yes
Cellular MOA of ADH on renal tubular cells
V2 receptors- activate adenylyl cyclase to increase cAMP and enhance water permeability
Cellular MOA of ADH on vascular smooth muscle
V1- stimulates influx of Ca ions and vasoconstriction
Describe the role AQP2 with ADH
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.
Lack of AQP2 causes what?
congenital or primary forms of diabetes insipidus
Over-expression of AQP2 causes what?
water retention and can be associated with SIADH, congestive heart failure, and pregnancy
Structure of AQP
6 transmembrane a-helices and N and C terminus on cytoplasm side. There are 5 inter-helical loop regions.
How does ADH acutely regulate permeability of distal collecting duct?
trafficking AQP2 from intracellular vesicles to apical membrane
_____ is a disorder defined by failure to concentrate urine as a result of decreased secretion of osmoregulated ADH.
Neurogenic/central DI
Clinical presentation of central DI
Polyuria day and night, thirst and polydipsia with preference for ice-cold water
Children: enuresis
Causes of central DI
Most are aqcuired: idiopathic, tumors, trauma, granulomatous disease, infection, cerebral vascular disorders
Can be familial
3 pathogenic mechanisms of polyuria
- Neurogenic DI
- Nephrogenic DI
- Primary polydipsia: psychogenic DI or dipsogenic DI
What will plasma and urine osmolarity look like with polyuria?
Neurogenic and nephrogenic DI- Plasma: high
Urine: low
Primary polydipsia: both will be low
How can you tell the difference between neurogenic, nephrogenic DI, and primary polydipsia?
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.
What clinical conditions are associated with elevated ADH?
CHF, cirrhosis, SIADH
What does SIADH do when there is normal water intake?
Cause hypo-osmolality and hyponatremia
Pathogenic mechanisms of SIADH
- Malignant tumors- lung carcinoma (80% due to SCC)
- nonmalignant pulm diseases. this type of hyponatremia is common in TB and pneumonia
- CNS disorders- release of ADH due to inflammation or lesion.
- Drugs
Why is there no edema in SIADH? (Euvolemic hyponatremia)
Na secretion is enhanced due to GFR and ANH. This prevents edema and HTN
Clinical and lab features of SIADH
Present with weight gain, weakness, lethargy, confusion–> convulsions and coma.
Labs: low levels of everything in serum
Urine: inappropriately concentrated with Na.
DDx with SIADH
- Hypovolemic hyponatremia: adrenal insufficiency, diarrhea, diuretic therapy, nephropathy
- Hypervolemic hyponatremia: edema
- Pseudohyponatremia: severe hyper-lipids, proteins, glucose.
- 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.
What is the consequence of biochemical similarity between ADH and OT?
OT as pharmacological doses can alter water regulation at kidney- water intoxication
What kind of behaviors has OT been associated with?
Non social: learning, anxiety, feeding, pain
Social: social memary, attachment, sexual behavior, bonding/trust, aggression
What social disorders has OT been associated with?
Autism and schizophrenia
Acute presentation of hyponatremia
Early: nausea, vomiting, headach
Late: seizure coma resp. arrest
Chronic presentation of hyponatremia
lethargy, confusion, cramps, neuro impairment
What does nicotine do to ADH secretion?
increase
Tx of SIADH
Remove underlying cause, fluid restriction, block renal tubular response, (hypertonic saline if you’re feeling on the edge)
What are vaptans?
ADH V2 antagonists
Why do you have to be careful in giving hypertonic saline to someone with SAIDH?
Risk of osmotic demyelination syndrome
