What are 5 mechanisms that regulate fluid and electrolyte balance in the body?
1. ADH - controls free H2O clearance
3. Renin-Angiotensin-Aldosterone System - Salt and volume
4. Atrial Natiuretic Hormone - salt and volume; responds to atrial stretch
5. Sodium appetite
Where does ADH come from?
1. It is made in the cell body of cells in the supraoptic nuclei of the hypothalmus
- Gene transcription --> mRNA
- Translation of mRNA on ribosomes
- Migration of protein formed to golgi, cleavage of signal piece
- Packaging into storage granules
2. Travels down the axon through the neurohypophyseal tract
- Post-translational processing of the precursor occurs
3. Stored and then released by terminal of cell in the posterior pituitary
- Depolaization, exocytosis occurs and both ADH and neurophysin are released in pars nervosa
Where are osmoreceptors found? Volume receptors?
Osmoreceptors: In the hypothalamus
Baroreceptors: Stretch receptors in major arteries (aorta, carotid, etc)
What controls the release of ADH?
Osmolality and volume
--> Osmolality trumps volume if there's a conflict
What neurotransmitters affect ADH release?
NE neurons are inhibitory to ADH release
Acetylcholine neurons are stimulatory to ADH release
What is the function and MOA of ADH?
As osmoreceptors signal increased osmolarity or volume receptors signal decreased volume, ADH is released by the pars nervosa
--> ADH acivates cell surface G-coupled proterin receptors on the distal tubule and collecting duct, activating adenylate cyclase and increasing the # of aquaporins present on the cell
--> this increases water reabsorption
What is Diabetes Insipidus?
Disorder in H2O metabolism due to relative or absolute loss of ADH or to an inability of ADH to exert its effects
What are the types of Diabetes Insipidus?
--> should not be confused with compulsive H2O drinking
What are treatment options for Diabetes Insipidus?
1. Neurohypophyseal, complete lack of ADH:
Treat with replacement ADH, DDAVP
2. Neurohypophyseal, partial lack of ADH:
Treat with agents that enhance ADH secretion and potentiate effects (i.e. Chlorpropamide)
What is SIADH?
1. Excessive H2O retention
2. Dilutional hyponatremia
3. Maximally and/or inappropriately concentrated urine
--> Depending on cause, ADH secretion may or may not vary in relation to plasma osmolarity and volume
What are the causes of SIADH?
- Change in the set point for ADH release (i.e. side effect of thoracotomy)
- Faulty stimuli from peripheral volume receptors (i.e Stroke)
- Ectopic ADH production (i.e. small cell carcinoma of lung - *most common*)
What are the three key symptoms of SIADH leading to diagnosis?
Inappropriately concentrated urine
Elevated levels of ADH
What are SIADH treatment options?
Remove cause if possible
Reduce H2O intake
Suppress ADH (dilantin)
Inhibit ADH action (receptor antagonists)
What are the treatment options for pituitary tumors?
1. Radiotherapy - focused proton beam
2. Surgery-transphenoidal hypophysectomy
3. Combined surgery and radiotherapy