lecture 17 (thrist) Flashcards
what are the types of thirst
2 types
osmometric thirst: hypertonic interstitial fluid (high salt meal)
volumetric thirst: low blood volume (hemorrhage)
what are the body fluid compartments
- intracellular compartments
- extracellular
- intravascular (in BV) /interstitial (not in vascular system)
describe what happens when you consume high salt meal (ie osmometric thirst)
- high salt meal > blood plasma = hypertonic > hypertonic intravascular fluid causes osmosis out of interstitial fluid to normalize > now interstitial fluid becomes hypertonic > water is pulled out of intracellular compartment > sensed by osmoreceptors in OVLT/PVN/SON (VP releasing areas)
describe how osmoreceptors work
osmoreceptors expresses stretch-inhibited ion ch (stretched > closing of ch)
- hypertonic condition cause shrinkage of osmosensitive cells > increases opening of ion ch > depolarization (increase firing rate)
- hypotonic > stretch of membrane > decrease opening ion ch > inhibit depol (less firing rate)
where are osmoreceptors located and why is this specialized?
Located in OVLT PVN SON
But is specialized cuz OVLT = circumventricular organ with fenestrated capillaries allow for detection of tonicity of the blood
what are magnocellular neurons
- cell bodies in hypothalamus PVN/SON
how does osmoreceptors correct hypertonic condition directly
- 2 mecs:
- increased release of VP (osmosensitive SON/OVLT neurons activated > project to SON/PVN to increase VP release)
- activation of neural circuits that mediate thirst (OVLT neurons also project through median preoptic nuc MPN - thirst center)
describe indirect mechanism for release of VP
- inhibitory interneurons monitor the size of OVLT osmoreceptors project to SON/PVN
- IN extend dendrites around osmoreceptors and acts as mechanoreceptors = IN decrease firing as os R shrink (due to hypertonicity of interstitial fl)
- with normal osmoreceptor cell volume (not shrink): interneuron inhibits VP release
describe “set point” for VP release? As a result…?
plasm os maintained within narrow limits > under a certain threshold, VP not released
- above the point VP is released in a linear fashion in relation of plasm os
- plasma [VP] increases before thirst is felt: meaning VP neurons more sensitive to os R output from OVLT than MPN
describe exception to the linearity VP release
- rapid changes of plasm os > exaggerated VP release higher than predicted by linear
- decrease VP while drinking (we can drink way faster than water can be absorbs into the system and signals to brain so decrease VP > prevent overdrinking )
- during gestation os threshold for VP release is lowered
what are the different inputs that elicits volumetric thirst
- baroreceptors in carotid sinus
- atrial baro R in heart and large BV
- JG cells in kidneys
how does baroreceptors in carotid sinus signal volumetric thirst
baro R decreases FR with decreased BV (decrease BP) > these receptors project to NTS > NTS sends projection to SON/PVN > increases release of VP > causing reabsorption water in kidneys
- ALSO NTS sends projections to MPN > elicits thirst
how does atrial baro R signal volumetric thirst
same way as carotid sinus baro R but less responsive > requires large change in pressure > induce large increase in VP + innervates large number of NTS > HUGE magnitude of response (experimentally confirmed in dogs)
how does JG cells signal volumetric thirst
- kidneys monitor blood flow (decrease BF indicates decrease BV) > decrease flow causes JG cells to release renin into BS ?????
- JG cells located near glomerulus and activates and release renin in response to drop in BP/decrease plasma sodium levels (direct)
- JG cells receive inputs from SNS
- expresses b adrenergic R (binding of NE > renin release) (indirect)
what does renin do
- renin is protease (enzyme) > cleaves angiotensinogen > angiotensin 1 (dont do much) > cleaved again > angiotensin 2 (active)
describe the angiotensinogen pathway
angiotensinogen is prohormone always found in blood > renin is released (rate limiting) > cleaves angiotensinogen and forms angiotensin 1 (not active) > in lungs angiotensin converting enzyme (ACE) chops 1 to form 2
what happens when theres conflicting input from os vs vol
conflicting input to neurons of SON and PVN (ie hyponatremia and low BV): osmotic control overrides volemic mechanisms (other mechanisms can support blood volume)
how does body choose baro vs osmo
while both baro R and os R both project to SON/PVN, different receptors form synapses on different part of the target neuron
- baro R input synapse on most distal dendrits
- os R input synapse near axon hillock = closer to axon hillock = greater effect on if an action potential will fire
(can inhibit any baroreceptor act. of VP release)
describe over night deprive water experiment
- people are deprived of water overnight = exhibit both osmotic + volemic thirst > in the morning either IV water or IV isotonic saline
- if IV injection water > osmosis out of vasculature and into dehydrated cells can take up the water > no osmotic thirst but volumetric thirst remains
- individuals in this group experience significantly less thirst than water deprived control (85% less water)
- if IV inject isotonic saline > replenishing the volume but not osmos into cells > still have osmos thirst but not vol thirst
- these individuals drank (25% less water than control)
- osmotic thirst more powerful
how do we know when we’re no longer thirsty?
- satiety mechanism for thirst is independent of detection of dehydration
- amount of water consumed depends on input from several peripheral sources ie oropharynx/digestive
- prevents overdrinking
describe the ang 2 receptors
GPCR
AT1 R (most effects on fluid balance are mediated by AT1 R) expressed in SFO/OVLT, pituitary, vascular SM. kidney
- couples to Gq > stim PLC
AT2 R important during development
ang 2 binds at AT1 R to mediate
Vasopressin release
Water drinking
Sodium retention
Sodium appetite
Vasoconstriction
ACTH release
what is ang 2 how does it signal to brain
- dipsogen (increase thirst measured by drinking behavior in animals)
- too large to cross BBB
- binds to R in SFO > SFO neurons projects (increase firing rate) to MPN and SON/PVN
how is ang 2 important to the homeostasis of Na
- volumetric thirst requires replenishment of water and sodium
- Volumetric thirst occurs with loss of blood volume without a change in the osmolarity of the blood
- if only water is replenished then the osmolarity of blood would decrease
- Angiotensin II causes retention of sodium as
well as water with volumetric thirst
