Lecture 24: Osmolarity and Blood Volume Flashcards
what is normal osmolarity
appx 280 mOsm
explain how hypertonic ECF causes release of ADH
- aquaporin channels in hypothalamic neurons (osmoreceptors) allow water to exit cells by osmosis
- osmoreceptors shrink
- stretch sensitive channels open allowing entry of Ca and Na –> causes depolarisation and AP generated
- AP passed to SONs and PVNs which then release ADH into post. pit.
explain the MoA of ADH
- ^ water reabsorption at DCT and CD
- by ^ the aquaporins present in walls of CD and DCT
describe the effect a hypotonic ECF has on ADH release
- aquaporins in hypothalamic neurons (osmoreceptors) allow water to enter cells by osmosis
- osmoreceptors expand
- stretch channels inactivate
- decrease in Ca and Na entry therefore no AP
- SONs and PVNs not activated
- decrease in ADH release
- less water reabsorption at CD
- ^ ECF osmolarity
explain how normal blood pressure inhibits ADH release
- baroreceptors in carotid sinus and aortic arch sense stretch of BV wall
- baroreceptors activate w/ each heart beat allowing Ca and Na to enter and depolarise nerve cell
- AP transmitted to hypothalamus
- Normal BP inhibits SON and PVN dependent release of ADH
outline how reduced BP causes release of ADH and the effect ADH has on BP
- reduced BP means reduced AP firing rate
- SON and PVN not inhibited
- ^ ADH release
- ^ water reabsorption
- ^ BP
what type of hormone is aldosterone and where is it released from
mineralocorticoid released from Zona Glomerulosa of adrenal cortex
what causes release of aldosterone
- ^ plasma K+
- ^ ACTH
- ^ ang2 (renin)
- dec. plasma pH
- dec. atrial stretch
- dec. BP
what does release of aldosterone cause
- ^ Na+ and H2O reabsorption
- ^ K+ secretion
(via ^ Na/K ATPase expression)
describe action of aldosterone in response to hyperkalaemia
- ^ expression of Na/K ATPase pump in DCT and CD
- drives a net secretion
- therefore more K+ excreted
what is Conn’s disease
primary hyperaldosteronism
what can cause Conn’s disease
adrenal adenoma
what is secondary hyperaldosteronism
over activity of RAAS
name a result of both primary and secondary hyperaldosteronism
arterial hypertension assc w/ hypokalaemia
name some causes of primary hypoaldosteronism
- primary adrenal insufficiency
- congenital adrenal hyperplasia
- side effects of meds e.g. ACE inhibitors or some diuretics
describe some results of hypoaldosteronism
- hyperkalaemia
severe: - palpitations
- muscle weakness
- numbness
- abnormal heart rhythms
- cardiac arrest
- death
name types of hypo aldosteronism
- primary
- secondary
- isolated
what is isolated hypoaldosteronism
reduced aldosterone w/o corresponding changes in cortisol
describe some cause of secondary hypoaldosteronism
- disease of pituitary or hypothalamus (dec. ACTH)
- dec. ang2 prod.
- renal diseases e.g. diabetic nephropathy
- drugs e.g. NSAIDs, cyclosporine
how do you differentiate the cause of hypoaldosteronism
- ACTH stimulation test for aldosterone
- -> low aldosterone response = primary
- -> normal/large response = secondary
outline how dec. ECF osmolarity activates the RAAS
- dec. ECF osmolarity = dec. plasma Na+
- dec. plasma reabsorption
- detected by kidneys which release renin
- angiotensinogen converted to ang1
- ACE in lungs conerts ang1 to ang2
- ang 2 acts on adrenal cortex causing release of aldosterone
- aldosterone ^ Na/K ATPase pump expression in DCT and CT
- ^ Na+ reabsorption
outline how ^ SNS activity activates RAAS
- ^ SNS
- renin released
- angiotensinogen –> ang1
- ang1 –> ACE (lungs) –> ang2
- ang2 –> adrenal cortex
- aldosterone release
- pump expression ^
- ^ Na+ reabsorption (and H2O)
- ^ blood volume, BP and CO
what can negatively feedback to ^ ECF osmolarity after activation of RAAS and how is it caused
^ blood volume
- ang2 acts on brain to release ADH which ^ H2O reabsorption causing ^ blood volume
what can activate RAAS
- dec. ECF osmolarity
- ^ SNS activity
how is the negative feedback of ^ blood volume for dec. ECF osmolarity overcome
hypothalamus overrides effects of ang2 thus causing a dec. in ADH release therefore dec. H20 reabsorption
explain regarding juxtaglomerular cells how low Na+, BP AND/OR SNS activity affects release of renin
low Na+
- low Na+ in filtrate
- low Na+ reabsorption into macula densa
- sensed –> prod of PGE2
- goes to juxtag. cell
- renin prod by these cells and released into blood
SNS
- SNS release noradrenaline onto B1 receptors on juxg. cell
- prod of cAMP
- prod renin
BP
- ^ BP
- stretch sensitive channels in juxg. cells
- cause down regulation of cAMP
- inhibits renin release
- BP dec.
how does ^ BP affect Na+ reabsorption
reduces reabsorption
outline the effect of ^ ANP on renin release and blood volume
- ^ ANP from atrial myocytes due to atrial distension
- ANP inhibits renin release
- -> dec. circulating ang2 and aldosterone (natriuresis and diuresis - K+ sparing as K reabsorption maintained)
- ANP ^ GFR (diuresis)
- ANP dec. Na transporter activity in loop (non K+ sparing natr/diuresis)
- systemic vasodilation (directly and indirectly)
- dec. blood volume, BP and CO
name a natural counter regulatory system for RAAS
natriuretic peptides
why is this mechanism useful in treatment of hypertension and CHF
doesn’t affect K+ levels in rest of body
when is thirst activated
when blood osmolarity ^^
when is thirst activated
- when blood osmolarity ^^
- inputs from blain (anticipation of food)
- inputs from body (sensing salt in mouth, hypovolaemia)
how does the kidney know what and how much to eliminate
- imbalance of homeostasis (stimulus)
- detected by sensor
- info sent to control centre
- effect produced
- response
which of these treatments for hypertension are working through RAAS and/or kidneys
- diuretics
- CCBs
- ACEi
- ang2 rec. antagonists
- B-adrenergic rec. antagonists
- vasodilators
- renin inhibitors
- aldosterone rec. antagonists
- A2 adrenergic rec. agonists
1, 3, 4, 5, 7, 8
2, 6 and 9 affect b.v.
