Lecture 14: Water and salt balance Part 1 Flashcards
Describe the negative feedback loop of ADH:
Water deficit -> Increased ECF osmolarity -> Osmoreceptors -> Increased ADH secretion -> Increased plasma ADH -> Increased water permeability DT and CD -> Increased water reabsorption and decreased water excretion (-ive feedback to water deficit)
Describe where ADH comes from:
ADH synthesised as part of precursor protein in hypothalamus, travels down axons to post. pituitary, wehere it is stored in granules in the nerve terminals. ADH is a nonapeptide
What determines ADH release?
Control of ADH release by osmolality and ‘volume’ of ECF
Where are osmoreceptors located?
Osmoreceptors in supraoptic and paraventricular nuclei sense high osmolality and result in stimulation of ADH release
What other regions of the brain contribute to ADH release? and how do they work?
Inputs to hypothalamus from the medullary vasomotor center increase ADH release in response to decreased circulating volume
Both initiate mechanisms that influence supraoptic and paraventricular ADH secreting neurons
What is the greater stimulus for ADH?
ADH is released in response to either increased osmolality (less than 1% chain) or decreased volume (greater than 10% change) of the ECF
Secretion of ADH in response to increased osmolality has a lower threshold and higher sensitivity (slope) than the response to decreased ECF.
What are the non-physiological stimuli for ADH secretion?
- Pain and stress
- Drugs: narcotics, nicotine
- Carcinomas
- Pulmonary disorders
- CNS disorders
- Alcohol (inhibits ADH secretion)
Describe the molecular mechanism of ADH:
ADH binds V2 receptor, increased cAMP -> PKA -> Phosphorylation and AQ2 insertion into apical membrane
What can develop if ADH is low?
Central and nephrogenic diabetes insipidus can develop if there is difficulty producing ADH or its action occuring.
What is central diabetes insipidus?
- AKA neurogenic DI or pituitary DI
- (Inadequate ADH secretion)
- Problem with hypothalamus or post. pituitary
- i.e due to brain injury, tumor or infection
- Rarely hereditary
- Treated with ADH analogues
What is nephrogenic DI?
- CT unresponsive to ADH
- Concentrated urine cannot be produced
- Can be caused by certain drugs, commonly Li
- Less commonly hereditary
- > Congenital defect in V2 receptor
- > Inherited defect in AQ2
- Not currently treatable
Whats the difference b/w diabetes insipitus and diabetes mellitus?
DM = glucose in urine DI = No glucose in urine
What is syndrome of inappropriate ADH secretion?
A defect in inappropriate ADH action
- High plasma ADH for osmolarity / volume
= Patients retain water inappropriately
= Patients have to be restrict water intake
What can cause SIADH?
- Brain injury
- Cancer
- Anti-cancer drugs
- Lung cancer
What does a decreased in BP stimulated?
Renin!
