homeostasis

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homeostasis
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Physiology

• In the distant past, humans thought that good
  health was somehow associated with a "balance"
  among the multiple life-giving forces ("humours")
  in the body
• Today we know that living tissue is composed of
  trillions of small cells, all are packaged to
  permit movement of certain substances, but not
  others, across the cell membrane.
• also we know that cells are in contact with the
  interstitial fluid.
• The interstitial fluid is in a state of flux,
  with chemicals, gases, and water moving it in two
  directions between the cell interiors and the
  blood.

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Fluid compartments of the body
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• most of the common physiological variables found
  in normal, healthy organisms are maintained at
  relatively steady states.
• i.e. blood pressure, body temperature, blood
  oxygen, and sodium.
• This is true despite external conditions that are
  not constant.

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Homeostasis defined

• homeostasis is simply defined as a state of
  reasonably stable balance between the
  physiological variables
• NO variable is constant over time.
• Blood glucose can have dramatic swings.
• Homeostasis is in DYNAMIC balance, not static.
• It is relatively stable, if disturbed mechanisms
  can restore it to normal values.

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What does it mean to be relatively constant?

• It depends on what is being monitored.
• Arterial oxygen must be tightly controlled
• Blood glucose can vary wildly
• A person can be in homeostasis for one variable
  but not for another.
• You could be in sodium homeostasis but have
  abnormally high levels of CO2.
• This is a life threatening condition.
• Just one variable out of homeostasis can have
  life-threatening consequences.

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Physiology vs. Pathophysiology

• If all your major organ systems are in
  homeostasis, then you are in good health.
• diseases take one or more systems out of
  homeostasis.
• PhysiologyWhen homeostasis is maintained
• Pathophysiology homeostasis is not maintained.

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How do you know if a variable is in homeostasis?

• You have to observe a person over time to find
  out what is normal.
• Not usually possible because you only go to a
  doctor when you are sick (out of homeostasis).
• Usually, doctors rely on normal values for large
  populations of people.
• Body temperature
• Normal values are useful, but not if a person has
  been exercising.
• There are rhythms to a persons body temperature.

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Many variables are cyclical

• Examples
• Body temperature,
• sleep/wake,
• levels of certain hormones
• If you took one measurement, they may be normal,
  but might not detect when they are abnormally
  high or low.
• Measure over 24 hour period to get a better
  picture of homeostasis.

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Characteristics of homeostatic control systems

• cells, tissue and organ activity must be
  integrated so that changes in the ECF initiate a
  reaction to correct the change.
• Homeostasis, then, denotes the relatively stable
  conditions of the internal environment
• These conditions result from compensating
  regulatory responses controlled by homeostatic
  control systems.

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Regulation of body temperature

• Man w/ body temp. of 370 C is in room at 200 C
• He is losing heat to the environment
• Chemical reactions in his cells are releasing
  heat at a rate to loss
• Body is in a steady state but state is maintained
  by input of energy
• Steady state is not equilibrium
• Steady state temperature is the set-point

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Lower room temp to 50 C

• This increases loss of heat from skin and body
  temp starts to fall
• What responses will occur?
• Blood vessels to skin constrict
• Person curls to reduce skin surface area
• Shivering occurs producing large amounts of heat

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Negative Feedback

• Defined
• an increase or decrease in the variable being
  regulated brings about responses that tend to
  move the variable in the direction opposite
  ("negative" to) the direction of the original
  change
• It can occur at the organ, cellular, or molecular
  level

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negative feedback example
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Negative feedback in an enzyme pathway

• When energy is needed by a cell,
• glucose is converted into ATP.
• The ATP that accumulates in the cell inhibits the
  activity of some of the enzymes involved in the
  conversion of glucose to ATP
• As ATP levels increase within a cell, production
  of ATP is slowed down

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Not all feedback is negative

• Positive feedback is less common but does occur
• In nerve cells, when a stimulus is received,
  pore-like channels open letting Na in
• In childbirth
• The babys head presses against the uterus
  stimulating the release of oxytocin
• Oxytocin causes uterine contractions, pushing the
  babys head against the uterine wall releasing
  more oxytocin.

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Feedforward regulation

• While your body can respond to changes in
  external temperatures AFTER the bodys internal
  temperature changes, it can also respond to
  changes BEFORE your body temp. starts to fall.
• Nerve cells in the skin detect changes and send
  information to the brain.
• Often this response is a result of LEARNING

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Parts of homeostatic control systems- Reflexes

• reflex is a specific involuntary,unlearned
  "built in" response to a particular stimulus
• The stimulus is a detectable change in the
  internal or external environment.
• Detected by a nerve receptor
• The stimulus causes the receptor to send a signal
  to the integrating center (afferent)

Reflex Arc
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Reflex part 2

• Integrating center receives signals from many
  receptors
• Receptors may be for different kinds of stimuli
• Output from center (efferent) goes to effector to
  alter its activity

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Reflex for minimizing decrease in body temperature
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Reflexes are not just part of the nervous system

• We usually think of reflexes are part of the
  nervous system (hand on a hot stove), but now we
  include many other systems as part of reflexes.
• Hormone-secreting glands serve as integrating
  centers
• Chemical messengers travel through the blood.

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Intercellular chemical messengers

• reflexes and other responses depend on the
  ability of cells to communicate w/ each other.
• Most often occurs with chemical messengers.
• Hormones- allow hormone secreting cell to
  communicate with target cells.
• Blood delivers the hormone to the cell.
• Neurotransmitters- allow nerve cells to
  communicate with each other
• One nerve cell can alter the activity of another
  cell.
• Neurotransmitters released into the area around
  effector cells can alter their activity.
• Paracrine agents- chemical messengers in local
  responses

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Categories of chemical messengers
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Paracrine/autocrine agents

• Paracrine agents are made by cells (given a
  stimulus) and released into the ECF.
• Agents diffuse to neighboring cells which are
  their target cells.
• Autocrine agents are made by a cell, released and
  the target cell is the one that released it. (?)

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Why do you care about these agents?

• We are finding many different paracrine/autocrine
  agents that have many diverse effects.
• They are not just proteins.
• Secreted by many cell types in many kinds of
  tissues
• So many that they can be organized into families
• i.e. Growth factor family has 50 distinct
  molecules that can cause cells to
  divide/differentiate.

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Processes related to homeostasis

• Some seemingly unrelated processes have
  implications for homeostasis
• Adaptation and acclimatization
• Biological rhythms
• Apoptosis

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Adaptation/ acclimatization

• Adaptation is a characteristic that favors
  survival in specific environments.
• Your ability to respond to a specific
  environmental stress isnt fixed, but it can be
  enhanced by prolonged exposure to the stress.
• Acclimatization A specific type of adaptation-
  the improved functioning of an existing
  homeostatic system.

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Acclimatization is reversible (usually)

• If daily exposure to the stress is eliminated,
  then acclimatization is reversible
• Some acclimatizations that happen early in life
  may become permanent.
• Natives of the Andes Mountains
• Low oxygen levels cause increased chest sizes,
  wide nostrils, broad dental arches

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Biological rhythms

• Many body functions are rhythmic
• Occur in 24 hour (circadian rhythm) cycles
• Sleep/wake, body temp., hormone levels, etc
• Are anticipatory (kind of like feedforward
  systems without detectors)

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Rhythms allow responses to occur automatically

• Remember that most homeostatic responses are
  corrective, they occur after homeostasis is
  perturbed
• Rhythms cause responses to occur when a challenge
  is likely but before it actually does.
• Urinary excretion of potassium is high during the
  day and low at night.

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Body rhythms are internally driven

• Environmental factors dont drive the rhythms,
  but provide timing cues.
• Sleeping experiment (no light cues)
• Sleep/wake cycle is a free-running rhythm
• Sleep/wake cycles can vary between 23-27 hours
  but not more or less than that.

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Other environmental cues

• Light/dark cycle is very important, but not the
  only one.
• External environmental temperature
• Meal timing
• Social cues
• Sleep experiment people are separated, their
  cycles are each different.
• Put them together and their cycles synchronize

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Jet Lag

• Environmental time cues can phase-shift rhythms.
• Going from LA to Atlanta and staying for a week.
• Circadian rhythm will adjust, but it takes time
• In the meantime, you suffer jet lag
• Sleep disruption, gastrointestinal trouble,
  decreased vigilance and attention span, general
  malaise

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Neural basis of body rhythms

• In the hypothalamus
• A group of nerve cells (suprachiasmatic nucleus)
• Acts as the pacemaker for rhythms
• Pacemaker receives input from the eyes and other
  senses.
• Then it sends signals to other parts of the brain
  that control other systems, activating some and
  inhibiting others.
• Not well understood

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Sleep and the Pineal gland

• Pacemaker sends signal to pineal gland
• Gland releases melatonin
• Pineal secretes during darkness, not daylight
• Melatonin influences other organs
• Makes you sleepy

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Apoptosis

• Defined-
• The ability to self-destruct by activation of an
  intrinsic program within the cell
• Important for
• sculpting a developing organism or
• Eliminating undesirable cells (cancerous)

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Importance of Apoptosis

• Crucial for regulating the number of cells in a
  tissue or organ.
• Control of cell number is determined by a balance
  between cell proliferation (addition of new cells
  by mitosis) and cell death (apoptosis)
• Neutrophils (cells alive)

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How does it occur?

• Controlled autodigestion of cell organelles.
• Enzymes breakdown the nucleus and then other
  organelles
• The cell membrane isnt digested.
• The cell sends out chemical signals that recruit
  phagocytic cells (cells that eat other cells).
• This is different than what happens when a cell
  is injured (necrosis)

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How is it kept off?

• Virtually all cells have the apoptosis enzymes.
• Why arent they turned on?
• A large number of molecules called survivor
  signals keep the cell from activating the
  enzymes.
• So most cells are programmed to commit suicide
  UNLESS they receive a signal to stay alive.
• Prostate gland cells will die if testosterone is
  not present

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What about cancer? Degenerative diseases?

• Cancer cells undergo uncontrolled cell
  proliferation.
• So the apoptosis enzymes are always turned off.
• In degenerative diseases (osteoporosis)
• The rate of cell death is higher than that of
  cell proliferation.
• Drugs that reduce rate of apoptosis

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Balance in the homeostasis of chemicals

• Most homeostatic systems control the balance of
  specific chemicals.

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3 states of total body balance

• Negative balance
• Loss exceeds gain, total amount of substance in
  body is decreasing.
• Positive balance
• Gain exceeds loss
• Stable balance
• Gain equals loss

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Water, sodium balance

• Water
• Stable balance is upset with excessive sweating.
• Restored by?
• Sodium (Na)
• Kidneys excrete Na into urine in approx.
  amounts of ingested daily.
• If intake were to increase dramatically, kidneys
  will excrete more in urine, but only so much can
  be excreted.
• If the increase is continued, it can have effects
  on other systems
• A small change in blood sodium has been linked to
  hypertension.

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A quick summary

• Homeostasis is a complex, dynamic process.
• It regulates the adaptive responses of the body
  to changes in external and internal environments.
  
• homeostatic systems require a sensor to detect
  changes and a means to produce a response.
• Responses can include muscle activity, synthesis
  of chemical messengers (hormones) and behavioral
  changes.
• All responses require energy.
• You get energy to respond from the food you eat.