LECTURE 12: HOMEOSTASIS

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Psy 137 Behavioral Endocrinology Lecture 4-5
Homeostatic Neuroendocrine Systems
Website http//mentor.lscf.ucsb.edu/course/summer
/psyc137/
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Historical Antecedents

• Claude Bernard (1813-1878)
• ability to maintain a relatively constant
  internal environment
• Walter Cannon (1929)
• Homeostasis the process by which the body
  maintains relatively constant internal milieu

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Overview

• Defining homeostatic systems
• Temperature regulation
• Omotic regulation
• Fluid (water)
• Sodium
• Energy regulation (next day)

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HOMEOSTASIS

• From the Greek, Standing the Same
• Individuals are motivated to maintain specific
  endogenous levels (a balance) of water, sodium,
  and other nutrients.
• The process by which animals maintain a fairly
  stable internal environment is called
  homeostasis.
• Organisms have acquired the ability to maintain
  conditions within their body that differ
  drastically from their environment.

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The thermostat is a common homeostatic device.
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What properties are needed for homeostasis?

• Most homeostatic systems operate like a
  thermostatically controlled heating and cooling
  system.
• To maintain homeostasis, a system requires
• Detection mechanism to detect any deviation from
  a set point.
• Mobilization mechanism to make changes to return
  to the normal range.
• Recognition system to recognize when the desired
  change occurs and feed back to stop the
  mobilization process.

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Overview

• Defining homeostatic systems
• Temperature regulation
• Omotic regulation
• Sodium
• Fluid (water)
• Energy regulation (next day)

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Importance of thermoregulation

• Consequences of overheating
• 1. cramps- painful spasms. Usually in legs,
  sometimes in stomach and arms. Stop what you are
  doing, rest and drink.
• 2. heat fatigue - you feel faint, your skin is
  cool and moist, pulse weak.
• 3. heat syncope- you are dizzy, pale, sweaty.
  Heart rate may be rapid.
• 4. heat exhaustion- body temp normal, skin cold
  and clammy, un-coordinated, nauseated. You may
  have a headache and feel dizzy.
• 5. heat stroke- Body temperature is above 103
  degrees, skin dry and flushed, pulse strong and
  rapid, mental state impaired and you are on you
  way to a coma.
• 6. Death-

Consequences of freezing just begins here
(without the unpleasant effects) i.e. feel
cold-gt disorientation-gt coma-gtdeath
Key point too hot or too cold dead!
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Temperature Regulation

• Body temperature normally regulated close to
  37ºC
• if goes below 30 or above 40 -gt death.
• Detectors
• Central peripheral receptors
• Hot and cold receptors on surface of the skin
• Detectors in several brain regions with the most
  important lying within preoptic nucleus of the
  anterior hypothalamus (POA)
• POA region increases firing rate when heated
• Warming leads to panting, sweating
• Cooling leads to huddling, shivering
• Electrical stimulation of POA leads to same
  behavior as heating lesioning POA results in
  loss of thermoregulation (and possible death)
• Ice cube to roof of mouth cools POA -- reduces
  sweating but sharp rise in temperature

Horizontal sections through the rat diencephalon
showing 281 neurons tested for thermosensitivity.
While the majority of neurons are located in the
preoptic region (shaded with diagonal lines),
thermosensitive neurons can be found throughout
the rostral-caudal extent of the hypothalamus.
Open circles warm sensitive neurons Open
triangles cold sensitive neurons Closed
circles temperature insensitive neurons. 3v
third ventricle ac anterior commissure fx
fornix mt mammillothalamic tract oc optic
chiasm on optic nerve ot optic tract. (From
Dean and Boulant, Am J Physiol 257 R57-R64,
1989.)
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Temperature Regulation

• Metabolic Effectors
• Thyroid releasing hormone (TRH) from PVN -gt
  thyrotropic hormones (TSH) from ant. pit -gt
  thyroxine (T4) triidothyronine (T3) from
  thyroid.
• Epinephrine release from adrenal medulla (ANS)
  controlled by hypothalamus

• Increase global cellular metabolism (i.e. more
  biochemical reactions per unit time) a.k.a.
  basal metabolic rate (BMR) resulting in more heat
  production.
• Sort of like a light bulb where action results in
  heat creation as a byproduct.

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Temperature Regulation

• Behavioral Regulation
• Cold-blooded animals regulate temperature by
  changing positions (cold -gt curl up hot -gt flail
  out)
• Warm-blooded animals (when cool -- fluff out hair
  or feathers when hot -- sweat, pant, or lick
  body)
• Gross movement
• Rats will press bar to turn on heat in cold
  environment
• Rats will bar-press to take shower if hot

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Behavioral Thermoregulatory Pathways

• Shivering pathway starts in POA and involves many
  descending brain structures.
• Also input to medial forebrain bundle (MFB) sends
  signal that it is cold to forebrain including
  limbic and motor circuits which can lead to
  behavioral changes to adjust body temperature
  (e.g. move where the temperature is different).

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Behavioral Fever Regulation
Behavioral regulation of body temperature
Post-inj 0-24 hr
Post-i 24-48hr
Pre-i
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Overview

• Defining homeostatic systems
• Temperature regulation
• Omotic regulation
• Fluid (water)
• Sodium
• Energy regulation (next day)

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Importance of water regulation

• 70 of our body is water
• 75 of Americans are chronically dehydrated
• Lack of water, is the 1 trigger of daytime
  fatigue.
• In 37 of Americans, the thirst mechanism is so
  weak that it is mistaken for hunger.
• A mere 2 drop in body water can trigger fuzzy
  short-term memory, trouble with basic math, and
  difficulty focusing on the computer screen or on
  a ! printed page.
• Even MILD dehydration will slow down one's
  metabolism 3 one glass of water will shut
  down midnight hunger pangs for almost 100 of the
  dieters
• 8-10 glasses of water a day could significantly
  ease back and joint pain for up to 80 of
  sufferers.
• to conserve water -gt vasopressin antidiuretic
  hormone (ADH) -gt-gtraises blood pressure by
  constricting blood vessels.

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Water largest constituent of body 55-65 of
body weight

• Intracellular Fluid
• 66.6
• Within cells
• High potassium

• Extracellular Fluid
• 33
• Interstitial, space surrounding cells
• Intravascular 7-8 of total body water, 20-25
  of ECF
• High sodium

Osmotic pressure (concentrations of all solutes
in a fluid compartment) is equivalent between ECF
and ICF compartments
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Movement of water Osmosis
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Fluid Regulation

• General
• Water continually ingested, excreted and secreted
  to remove wastes and regulate temperature.
• Animals can maintain water balances within narrow
  limits (.22 of body if water available).
• Below 0.5, thirst results.

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Regulations of sodium and water intakes are linked
The kidneys use sodium to conserve water
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Two Kinds of Thirst
(cellular dehydration)
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OSMOTIC THIRST

• Movement of fluid out of cells causes cellular
  dehydration, a potent stimulus for osmotic
  thirst.
• Consumption of salty or sugary foods induces
  osmotic thirst.
• Cellular dehydration of osmoreceptors in the
  brain causes ADH secretion from the posterior
  pituitary, which promotes water conservation by
  the kidneys.
• Drinking water alleviates osmotic thirst.

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Osmoreceptors stimulate ADH secretion from PVN
and SON.
The vascular organ of the lamina terminalis
(OVLT) contains osmoreceptive neurons also the
subfornical organ (SFO) and the median preoptic
n. (MnPO)
These cells project to the PVN and SON to produce
AVP secretion
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Interfering with AVT balance can have
disastrous consequences

• AVT (amphibian equivalent of AVP/ADH)
• Affects kidneys to decrease water loss
• Promotes reabsorption from bladder
• Promotes water absorption across skin

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Osmotic homeostasis
The initial response to cellular dehydration is
release of arginine vasopressin (AVP) the
antidiuretic hormone AVP is synthesized in the
supraoptic n. and paraventricular n. of the
hypothalamus and transported along axons to the
posterior pituitary. AVP is stored in secretory
granules in posterior pituitary until an increase
in osmolality of body fluids initiates its
secretion into the blood AVP acts on V2 receptors
in the kidney to increase water permeability by
inserting aquaporin channels into cell
membranes Water moves out of the distal
convoluted tubule of the kidney by osmosis
through these channels decreasing
osmolality There is also an increased water
reabsorption by the kidney and decrease in
urine flow
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Osmotic homeostasis
Changes in the osmolality of plasma lead to AVP
secretion at a much lower threshold than they
lead to thirst Very small increases in AVP lead
to very large changes in urine volume Thus the
kidney is the first line of defense against
cellular dehydration Ongoing behavior is not
disrupted by thirst unless the buffering effects
of osmosis and antidiureses are insufficient
Buffer between water retention and water need for
intake. -reason why diuretics (alcohol caffeine)
are very bad for causing dehydration.
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Osmoreceptors Motivational responses

• OVLT projects
• to PVN to stimulate ADH secretion.
• to LH to stimulate motivational responses via
  limbic circuit.

LH
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VOLEMIC THIRST

• Caused by reduced blood volume (hypovolemia).
• Quenching volemic thirst requires ingestion of
  water, sodium, and other solutes.
• Hypovolemia stimulates the production of
  angiotensin II, a potent vasoconstrictor.
• Angiotensin II may also increase drinking
  behavior.
• Angiotensin II triggers the release of
  aldosterone from the adrenals aldosterone
  promotes sodium retention and subsequent water
  conservation by the kidneys.
• Aldosterone affects drinking behavior indirectly
  by its influence on osmotic thirst.

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Blood pressure maintained by two other mechanisms

• Capacitance or compliance of vascular system
• Arteries thick walled, veins thin walled
  distensible. Volume loss, veins collapse.
  Conversely, volume accumulates in veins when
  blood volume expanded
• Glomerular filtration rate by kidneys
• Drop in blood pressure reduces GFR decreases
  urine volume, whereas a rise in BP increases GFR
  and promotes urinary fluid loss. Kidneys so
  efficient that development of hypertension
  indicates renal dysfunction

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Volume homeostasis
Neural and endocrine signals of hypovolemia lead
to thirst and increased salt consumption
The renin-angiotensin system and AVP produce
antidiuresis and vasoconstriction Both
hypovolemia and hyperosmolality interact to
control AVP levels hypertension leads to
decreased AVP, whereas hypotension increases AVP
for a given plasma osmolality
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Volume homeostasis
Thirst is triggered by increased plasma
osmolality (OVLT receptors) , gastric salt load
(hepatic Na receptors), hypovolemia (angiotensin
II in SFO).
Thirst is inhibited by decreased plasma
osmolality (OVLT receptors) and by increased
blood pressure (hypervolemia)
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Volume homeostasis
Hypovolemia triggers not only thirst, but also
salt appetite Blood volume is corrected only by
replacing both water and salt Drinking water
alleviates thirst (by reducing plasma
osmolality), but triggers salt appetite, whereas
consuming salt triggers subsequent thirst (by
increasing plasma osmolality)
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Volume homeostasis
A loss of blood volume (hypovolemia) leads to
compensatory mechanisms, which include thirst and
increased salt consumption
Baroreceptors sense hypovolemia and cause kidney
to secret renin Renin interacts with
angiotensinogen to produce angiotensin I, which
is converted to angiotensin II (AII) AII is a
vasoconstrictor and promotes aldosterone
secretion from adrenal cortex and AVP secretion
by acting on the subfornical organ (SFO)
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Water will not quench volemic thirst
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Summary

• Body fluid homeostasis stability in the
  osmolality of body fluids volume of plasma.
• Mechanisms intrinsic to body fluids
  cardiovascular system
• Osmotic movement of water across cell membranes
  buffers ECF osmolality
• Osmotic movement of water across capillary
  membranes buffers acute changes in plasma volume
• Venous compliance
• Glomerular Filtration

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Overview

• Defining homeostatic systems
• Temperature regulation
• Omotic regulation
• Fluid (water)
• Sodium
• Energy regulation (next day)

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Sodium balance is mediated by physiology AND
behavior

• Rats that are sodium deficient from birth prefer
  sodium.
• Sodium preference appears to be hard wired
  (innate) (potassium also preferred).
• Post-ingestion consequences are important as
  well, but the animal makes a bee-line for sodium
  and this response is based on taste.

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Diet determines sodium appetite

• Herbivores
• Obtain sodium from plants (component of cells)
• But sodium content varies seasonally and from
  place to place.
• Carnivores
• The animals carnivores eat must maintain their
  own sodium balance. So the carnivores are not
  under the same salt pressures as herbivores.

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Behavioral Homeostasis

• Under normal conditions, physiological
  homeostasis maintains sodium balance (kidney,
  aldosteronesodium conservation).
• When physiological homeostasis fails, behavioral
  maintenance is often possible--appetite changes.
  
• (recall behavioral regulation of temperature in
  rat pups).
• Specific hungers

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Sodium Balance

• Sodium Intake
• Methodology
• Animal gets a choice between different tubes.
• In most preference tests there are just 2 tubes.
• In this case, the animal has a choice between
  water and normal saline (0.85).
• Fluid intake is measured daily and a preference
  is calculated.
• In this example, sodium is preferred over
  straight water by 67 (20/30).
• The preference threshold is the concentration at
  which preference over water exists. Detection
  threshold is the concentration at which the
  animal can tell the difference. These two
  parameters are not identical.

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Sodium Balance

• Preference threshold
• The concentration at which preference over water
  exists.
• Detection threshold
• The concentration at which the animal can tell
  the difference.
• These two parameters are not identical.

PT preference threshold AT aversion
threshold. Thus, the sodium deficient animal
drinks more sodium at low and at high
concentrations. The detection threshold is not
DIFFERENT for adrenalectomized (adx) and normal
animals. Both can detect the low salt
concentrations (Normals will discriminate to
avoid electric shocks).
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Behavioral Homeostasis is Fail-Safe Mechanism

• Adrenalectomized rats usually die within one
  week.
• If salt water or salt is offered to the animal,
  they survive as well as intact rats.
• Before adrenalectomy the animal drinks very
  little salt. Afterwards, salt intake increases
  dramatically.

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Blair-West et al., 1968 study

• Salt is frequently a defended resource among
  animals in the wild.
• B-W and colleagues studied bunnies (marsupials
  too) that ranged over several types of habitats.
  
• Snowy mountains (where the vegetation is
  naturally low in sodium)
• Desert (or seashore) (where the plants have high
  levels of salt).
• Observed morphological, physiological, and
  behavioral changes based on habitat

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Blair-West et al., 1968 study

• Snowy Mountain Rabbits
• Hypertrophied zona glomerulosa of the adrenal
  cortex.
• Aldosterone concentrations were high
• Aldosterone conserves salt.
• Urinary sodium content was very low (undetected)
• Voracious sodium appetite
• Desert Rabbits
• Narrow z. glomerulosa
• Low blood aldosterone
• High urinary concentrations of sodium
• No salt appetite.

When observed at low magnification (left) the
capsule (A), cortex (B), and medulla (C) are
visible. At higher magnifications (right) the
divisions of the cortex are visible Zona
glomerulosa - zg -with cells in small clusters
which secrete aldosterone, Zona fasciculata - zf
- with cells arranged in columns or strips which
secrete cortisol and Zona reticularis - zr -
with cells that are somewhat unorganized which
secretes sex steroids and may also secrete
cortisol. The medulla is the site of epinephrine
and norepinephrine production.
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Adaptation to specialized environments

• Rats (sodium chloride)
• Hamsters (saccharin)
• Kangaroo rats (efficiency in retaining water)
• Camels (pouch and metabolized water)

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Behavioral regulation of sodium balance

• Hamsters
• No matter what concentration of sodium is
  offered, hamsters never prefer saline over water.
  
• After adx, hamsters do not change preference and
  most die.
• If you put saccharine in with the salt they drink
  plenty of the saccharine NaCl and live.
• If given a choice NaCl or saccharine? Then,
  the hamster drinks saccharine and dies.
• Why?
• Hamsters evolved in the desert
• Finding sodium not a physiological problem
• No sodium appetite has evolved!

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Sodium Balance Generalities

• During pregnancy, more sodium is needed.
• Some environments have seasonal sodium
  availability.
• Several hormones react to sodium availability.