MPBP 301

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MPBP 301
Homeostasis
Bob Low Given D-207 656-4338 (W) 434-3132
(H) Bob.low_at_uvm.edu
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HOMEOSTASIS
Claude Bernard 1813-1878
"It is the fixity of the milieu interieur which
is the condition of free and independent life"
Unicellular vs Multicellular organisms
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HOMEOSTASIS
Walter Cannon(1871-1945)
"The highly developed living being is an open
system having many Relations to its surroundings.
. . changes in the surroundings excite Reactions
in this system, or affect it directly, so that
internal disturbances are produced. . . the
coordinated physiological reactions which
maintain most of the steady states in the body
are so complex, and so peculiar to the living
organism, that it is suggested that a specific
designation for these states be employed ---
homeostasis" -W.B. Cannon, 1929
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EQUILIBRIA THINK SWIMMING POOLS
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A USEFUL SELF-LEARNING MODULE

• http//physioweb.med.uvm.edu/homeostasis/

Design Patterns of Life Pools Balance Equilibria S
imple Feedback Complex Feedback
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DEFINITIONS

• Homeostasis
• Maintenance of a constant internal milieu in the
  face of environmental provocations and
  fluctuations
• Steady State
• Output rate (amount per time) Input rate
  (amount per time)
• Excretion Rate (mg/min) Production Rate
  (mg/min)
• Examples Most everything

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STEADY STATE

• Excretion Rate Production Rate

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CONTROL OF BLOOD SUGAR
The Glucose Tolerance Test
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CONTROL OF BLOOD SUGAR
The Glucose Tolerance Test Insulin Response
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Insulin Controls Plasma GlucosePathophysiology
of Diabetes mellitus

• NORMAL
• Eat sugar ? ?Plasma glucose ? ?Insulin
  secretion by pancreatic ? cells ??glucose uptake
  into cells ? ?Plasma glucose ? ?Insulin
  secretion
• DIABETES
• Lose ? cells ? Insulin deficiency ? Type 1
  Diabetes Mellitus
• ?Sensitivity to insulin ? Type 2 Diabetes
  Mellitus

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EQUILIBRIUM BALANCING INPUT AND OUTPUT
On average, skin renews itself every 28
days Muscle Half-life is about a week Bone
calcium is exchanged in days Regulatory enzymes
have half-lives of hours
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STEADY STATE IS AN EQUILIBRIUM
BUT
EQUILIBRIUM IS NOT ALWAYS HOMEOSTASIS
http//physioweb.med.uvm.edu/homeostasis/
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EQUILIBRIUM IS NOT ALWAYS WHAT WE WANT
WRONG LEVEL
http//physioweb.med.uvm.edu/homeostasis/
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Steady State pCO2 is Regulated By the Lungs

• CO2 Excretion Rate CO2 Production Rate ? pCO2
  40 mmHg (Normal Steady State)
• Exercise??CO2 Production ? pCO2 gt 40 mmHg ?
  ?Ventilation ??CO2 Excretion? pCO2 ? 40 mmHg
  (Normal Steady State)
• Smoking ? Lung Disease ? ?Functional ventilation
  ? ?Excretion rate? ?pCO2 gt 40 mmHg? Abnormal
  Steady State pCO2 50 mmHg (Abnormal Steady
  State)

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KEY CONCEPTS
NEGATIVE FEEDBACK Mechanism that
RESTORES abnormal values to normal
Reverses a change
POSITIVE FEEDBACK Mechanism that MAKES abnormal
values MORE ABNORMAL Strengthens or
reinforces a change
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NEGATIVE FEEDBACK Mechanism that RESTORES
abnormal values to normal
Reverses a change
THINK THERMOSTATS
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Negative Feedback Control System
Thermostat
Desired Temperature
Heater/Cooler Heat if ? gt 0 Cool if ? lt 0
Temperature of Room
Actual Temperature
Actual Temperature
Thermostat
Integration center or comparator is hard-wired
with the set point or the target value for an
environmental condition and can compare input
from the sensor to the set point value. When the
input deviates from set point (error detector)
then the integration center initiates a response.
Sensor element (e.g., thermostat) measures and
monitors the actual value of some aspect of the
internal environment. For example, the
physiological thermostat measures the temperature
of the blood as it flows through the
hypothalamus.
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KEY CONCEPTS
POSITIVE FEEDBACK Mechanism that MAKES abnormal
values MORE ABNORMAL Strengthens or reinforces
a change
Angiotensin and salt / water balance Ovulation Dig
estion of food (Blood Clotting)
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Positive Feedback in Physiology

• Rare because it is intrinsically unstable
• Must be either carefully controlled, short-lived,
  and/or have a braking system
• Most common examples
• Yawning, Laughing, Sneezing
• Vomiting, Bowel Movement
• Pariturition
• Ends abruptly
• Physiological Example Sneeze
• Pathological Example Anaphylaxis
• Female Menstrual Cycle
• Positive feedback of estrogen on itself
• LH surge

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NORMAL STEADY STATE IS NOT ALWAYS WHAT WE WANT
Some times the RIGHT level should change
Thyroid Hormone / Fasting Cortisol / Stress
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KEY CONCEPT SETPOINTS
IF FEEDBACK SYSTMS ARE WORKING WELL, THE HORMONE
/ FUNCTION BEING REGULATED CANT CHANGE. BUT
WHAT IF IT SHOULD HAVE TO CHANGE TO MAINTAIN
HOMEOSTASIS?
SETPOINT
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FEEDBACK MAKING MAPLE SYRUP
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CONTROL SYSTEMSBang-Bang Control
Bang-Bang Control in a Public Bathroom Sink Try
to get Warm water by rapidly alternating your
hands between Freezing Cold faucet and Scalding
Hot faucet
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CONTROL SYSTEMSBang-Bang Control

• Goal Keep a bowling ball in the middle of the
  alley
• Bang-Bang Control
• Smack ball back and forth from gutter to gutter
• The average position of the ball is in the
  middle, but
• The ball spends almost no time actually in the
  middle
• Negative feedback using a control system that
  detects and corrects for a small error is better

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KEY CONCEPT FEEDBACK SYSTEMS MUST BE RAPID
RESPONSE
Good signal mechanisms must be Turned on AND OFF
rapidly.
The rate at which the level of a
substance Changes is determined by its rate
of degradation
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A SOLUTION
FEEDBACK LOOPS EMBEDDED WITHIN FEEDBACK
LOOPS Concept as soon as a response is set In
motion, steps are taken to immediately start
turning it off
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HOMOLOGOUS RECEPTOR REGULATION RECEPTOR
MODIFICATION
PHOSPHORYLATION CAUSES UNCOUPLING /
DESENSITIZATION RAPID SECONDS / MINUTES
More to follow later
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Why?
GOOD SIGNAL MECHANISMS MUST BE TURNED ON AND OFF
RAPIDLY REDUCING THE ERROR SIGNAL
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HOMOLOGOUS RECEPTOR REGULATION A KEY STRATEGY

• Examples
• Desensitization in neurotransmission
• Chronically elevated levels of insulin
• Lead to loss of insulin receptors

More to follow
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THE PHYSIOLOGY OF SURFACE RECEPTOR REGULATION
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RECEPTOR NUMBER
RECEPTOR NUMBER
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A USEFUL SELF-LEARNING MODULE

• http//physioweb.med.uvm.edu/homeostasis/