HOMEOSTASIS
"It is the fixity of the milieu interieurwhich is the condition of free and independent life"
Claude Bernard1813-1878
Unicellular vs Multicellular organisms
HOMEOSTASIS
"The highly developed living being is an open system having manyRelations to its surroundings. . . changes in the surroundings exciteReactions in this system, or affect it directly, so that internal disturbancesare produced. . . the coordinated physiological reactions which maintainmost of the steady states in the body are so complex, and so peculiarto the living organism, that it is suggested that a specific designationfor these states be employed --- homeostasis"
-W.B. Cannon, 1929
Walter Cannon(1871-1945)
EQUILIBRIA: THINK SWIMMING POOLS
http://physioweb.med.uvm.edu/homeostasis/
A USEFUL SELF-LEARNING MODULE
Design Patterns of LifePoolsBalanceEquilibriaSimple FeedbackComplex Feedback
– 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
DEFINITIONS
STEADY STATE
Excretion Rate = Production Rate
CONTROL OF BLOOD SUGAR
The Glucose Tolerance Test
GLUCOSE
CONTROL OF BLOOD SUGARThe Glucose Tolerance Test: Insulin Response
GLUCOSE
INSULIN
Insulin Controls Plasma [Glucose]Pathophysiology 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
EQUILIBRIUMBALANCING 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
EQUILIBRIUM IS NOT ALWAYSHOMEOSTASIS
STEADY STATE IS ANEQUILIBRIUM
BUT
http://physioweb.med.uvm.edu/homeostasis/
WRONG LEVEL
EQUILIBRIUM IS NOT ALWAYSWHAT WE WANT
http://physioweb.med.uvm.edu/homeostasis/
Steady State pCO2 is Regulated By the Lungs
• CO2 Excretion Rate = CO2 Production Rate pCO2 = 40 mmHg (Normal Steady State)
• ExerciseCO2 Production pCO2 > 40 mmHg Ventilation CO2 Excretion pCO2 40 mmHg (Normal Steady State)
• Smoking Lung Disease Functional ventilation Excretion rate pCO2 > 40 mmHg Abnormal Steady State pCO2 = 50 mmHg (Abnormal Steady State)
NEGATIVE FEEDBACK:Mechanism that RESTORESabnormal values to normal
Reverses a change
POSITIVE FEEDBACK:Mechanism that MAKES abnormal values MORE ABNORMAL
Strengthens or reinforces a change
KEY CONCEPTS
NEGATIVE FEEDBACK:Mechanism that RESTORES abnormalvalues to normal
Reverses a change
THINK THERMOSTATS
Negative Feedback Control System
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.
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.
Heater/CoolerHeat if > 0Cool if < 0
Temperatureof Room
DesiredTemperature
ActualTemperature
Thermostat
Thermostat
ActualTemperature
POSITIVE FEEDBACK:Mechanism that MAKES abnormal valuesMORE ABNORMAL
Strengthens or reinforces a change
KEY CONCEPTS
Angiotensin and salt / water balanceOvulationDigestion of food(Blood Clotting)
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
Some times the “RIGHT” level should change
“NORMAL” STEADY STATE IS NOT ALWAYSWHAT WE WANT
Thyroid Hormone / Fasting; Cortisol / Stress
KEY CONCEPT: SETPOINTSIF FEEDBACK SYSTMS ARE WORKING WELL,THE HORMONE / FUNCTION BEING REGULATED“CAN’T” CHANGE.
BUT WHAT IF IT SHOULD HAVE TO CHANGETO MAINTAIN HOMEOSTASIS?
SETPOINT
FEEDBACK: MAKING MAPLE SYRUP
CONTROL SYSTEMSBang-Bang Control
Bang-Bang Control in a Public Bathroom SinkBang-Bang Control in a Public Bathroom Sink::Try to get Warm water by rapidly alternating your Try to get Warm water by rapidly alternating your
hands between Freezing Cold faucet and hands between Freezing Cold faucet and Scalding Hot faucetScalding Hot faucet
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
The rate at which the level of a substanceChanges is determined by its rate ofdegradation
Good signal mechanisms must beTurned on AND OFF rapidly.
KEY CONCEPTFEEDBACK SYSTEMS
MUST BERAPID RESPONSE
A SOLUTION
FEEDBACK LOOPS EMBEDDEDWITHIN FEEDBACK LOOPS
Concept: as soon as a response is setIn motion, steps are taken to immediatelystart turning it off
HOMOLOGOUS RECEPTOR REGULATIONRECEPTOR MODIFICATION
PHOSPHORYLATION CAUSESUNCOUPLING / DESENSITIZATION
RAPID: SECONDS / MINUTES
More to followlater
Why?GOOD SIGNAL MECHANISMS MUSTBE TURNED ON AND OFF RAPIDLY
REDUCING THE ERROR SIGNALWITHOUT“INTERNAL”FEEDBACK
WITH“INTERNAL”FEEDBACK
HOMOLOGOUS RECEPTORREGULATION: A KEY STRATEGY
Examples:
Desensitization in neurotransmission Chronically elevated levels of insulin Lead to loss of insulin receptors
More to follow
H + R HR
THE PHYSIOLOGY OF SURFACE RECEPTOR REGULATION
RECEPTORNUMBER
RECEPTORNUMBER
H + R HR
http://physioweb.med.uvm.edu/homeostasis/
A USEFUL SELF-LEARNING MODULE