homeostasis

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.

Fluid compartments of the body

• 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.

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.

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.

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.

• Physiology:When homeostasis is maintained

• Pathophysiology: homeostasis is not maintained.

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 person’s body temperature.

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.

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.

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

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

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

negative feedback example

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

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 baby’s head presses against the uterus stimulating the release of oxytocin

• Oxytocin causes uterine contractions, pushing the baby’s head against the uterine wall releasing more oxytocin.

Feedforward regulation

• While your body can respond to changes in external temperatures AFTER the body’s 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

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

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

Reflex for minimizing decrease in body temperature

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.

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

Categories of chemical messengers

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. (?)

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.

Processes related to homeostasis

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

Adaptation/ acclimatization

• Adaptation is a characteristic that favors survival in specific environments. – Your ability to respond to a specific

environmental stress isn’t 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.

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

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)

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.

Body rhythms are internally driven

• Environmental factors don’t 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.

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

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

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

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

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)

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)

How does it occur?

• Controlled autodigestion of cell organelles.– Enzymes breakdown the nucleus and then other

organelles• The cell membrane isn’t 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)

How is it kept off?

• Virtually all cells have the apoptosis enzymes.– Why aren’t 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

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

Balance in the homeostasis of chemicals

• Most homeostatic systems control the balance of specific chemicals.

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

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.

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.