Homeostasis /
Allostasis
• Stability of systems that • Adaptation to changing
maintain life
external and internal
environment
– pH
– concentration of
different ions in the
extracellular fluid (Na+,
Ca2+)
– osmolality of
extracellular fluid
– glucose levels
– arterial oxygen tension
Constantly present
arterial blood pressure
heart rate
body core temperature
concentration of
circulating hormones
– sleep-wake cycle
– energy metabolism
–
–
–
–
Temporary process, e.g. under stress
Osmoregulation
Bourque, Nature Reviews, 2008, 9: 519-531
Osmoregulation
– Changes in ECF-osmolality cause H2O to flow
across cell membranes to equilibrate the
osmolality of the cytoplasm with that of the ECF
• Altering cell volume and ionic strength
– Danger for the brain, encased in the skull
– Osmoregulators: maintain ECF osmolality constant
around a set-point (300 mOsm / Kg)
osmoconformers
osmoregulators
osmoconformers
Osmoregulation
• Values measured in an individual varies around
the set point ± 3% range is normal
– Changes in water evaporation or diuresis
– Changes in salt excretion or intake
Diuresis
Natriuresis
• Receptors generate a basal signal and encodes
the polarity and the magnitude of a change
• Receptors found in the brain and gastrointestinal
tract
– GI-tract: anticipatory osmoregulation
• changes before plasma osmolality increase.
•
Information reach the brain through the vagus and
Nucleus tractus solitarius
Osmoregulation: hyper-, hypoosmolality
• ECF hyperosmolality
–
–
–
–
–
stimulates the sensation of thirst
activates the release of vasopressin
increases natriuresis
inhibits exercise-induced sweating
ev. inhibits salt appetite
• ECF hypoosmolality
– suppress basal vasopressin secretion
– Increased diuresis
– Inhibiting desire to drink
promotes water intake
enhances water readsorption
decreases Na excretion
decreases water loss
decreases Na absorption
Osmoregulation: brain
• The brain possess an intrinsic osmoreceptor
– OVLT
• Lesion experiments
• Direct injection of hypertonic solutions
• Electrophysiologic recording
• Modulates thirst and vasopressin secretion
• FMRI-studies show activation of the anterior
region of the 3d ventricle during the onset of
hypertonicity
Osmoregulation: receptors
• Osmoreceptors are specialized neurons with
intrinsic ability to transduce osmotic
perturbations into changes in the rate or
pattern of action potential discharge
– Detect differences between ECF-osmolality and a
pre-established set-point
– Encode this information in electrical signals
• OVLT, SFO and supraoptic nucleus
• Basal electrical activity encodes the osmotic set-point
excited by hypertonic ECF
inhibited by hypotonic ECF
Osmoreception: cellular mechanism
– Osmotic stimuli modulate nonselective stretch activated cation
channels
– Osmosensory transduction is a
mechanical process
• Increase in cation conductance caused
by hypertonicity leads to decrease in
cell volume
• Osmosensor display reversible changes
in volume that are inversely
proportional to ECF-osmolality
Osmoreception: cellular mechanism
• Stretch inactivated cationic channels
transduce osmoreception
Osmoregulation: the transducer
• C. elegans mutant for osm-9 lack avoidance to
strongly hyperosmolar solutions
• Member of the transient receptor potential (TRP)
vanilloid channels
– Knock-out mice for TRP1 and TRP4
Under hyperosmotic conditions:
• impairment in vasopressin secretion
• reduced drinking
• decreased cFos expression in the OVLT
• Actin network is required for osmosensory
transduction
• link to channels
• volume dependent strain
deformations of the membrane
Osmoregulation: CNS integration
• Integration with other visceral sensory modalities such
as blood volume, blood pressure, ECF Na+
concentration and body temperature
in thirst and diuresis
– Extracellular thirst: decrease of volume Changes
Changes in sodium appetite and natriuresis
– Intracellular thirst: increase of osmolite concentration
• Different types of osmotic perturbations require
different combinations of physiologic responses
– Hypovolemia activates the renin-angiotensin system and inhibit
natriuretic peptide. Thirst elicited by AII effect on the SFO which controls
the secretion of ADH from the posterior pituitary lobe. Decrease of fluid
output.
– Increased osmolite concentration activates OVLT and SFO and other
peripheral osmoreceptors. Integration in higher brain centers. Thirst.
Osmoregulation
Osmoregulation: thirst
• Water ingestion satiates sensation of thirst in
seconds, well before ECF osmolality is
corrected
Anterior cingulate cortex
motivate behavioural responses
demanded by particular homeostatic mechanisms
Insula
genesis of speecific homeostatic
sensations: pain, hunger and thirst
Osmoregulation: salt appetite
• Central pathways are not well known
Parabrachial nucleus and
Nucleus tractus solitarius
inhibit salt appetite
Osmoregulation: natriuresis
• Natriuresis controlled by various hormones
(aldosterone, AII, ANP) and the sympathetic
nervous system
Kidney innvervated polysynaptically from
the OVLT, MnPO, PVN, VLM, IML and sympathetic
neurons
Retrograde tracing with
pseurdorabies virus
Osmoregulation: work in progress
• Molecular structure of osmoreceptor (stretch
sensitive cation channel) is unknown
• Nature of cytoskeleton involvement remains
to be elucidated
• Acute versus chronic osmotic perturbation
• Neural mechanisms whereby thirst and salt
appetite become perceived at a conscious
level