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BIOM*3200 – Mammalian Physiology
UNIT 1 – Homeostasis and Neurophysiology
Pp. 4 - 8, 146 - 150, 160 – 180
Development of Pharmaceutical Drugs
•Biomedical research is often aided by animal models of particular diseases.
•These are strains of laboratory rats and mice that are genetically susceptible to particular
diseases that resemble human diseases.
•In phase I clinical trials, the drug is tested on healthy human volunteers.
•This is done to test its toxicity in humans and to study how the drug is “handled” by the body:
how it is metabolized, how rapidly it is removed from the blood by the liver and kidneys, how it
can be most effectively administered, and so on.
•If significant toxic effects are not observed, the drug can proceed to the next stage.
•In phase II clinical trials, the drug is tested on the target human population (for example, those
•Only in those exceptional cases where the drug seems to be effective but has minimal toxicity
does testing move to the next phase.
•Phase III trials occur in many research centers across the country to maximize the number of
•At this point, the test population must include a sufficient number of subjects of both sexes, as
well as people of different ethnic groups.
•If the drug passes phase III trials, it goes to the Food and Drug Administration (FDA) for
•Phase IV trials test other potential uses of the drug.
Homeostasis and Feedback Control
•A state of relative constancy of the internal environment is known as homeostasis
History of Physiology
•The American physiologist Walter Cannon (1871–1945) coined the term homeostasis to describe this
•Cannon further suggested that the many mechanisms of physiological regulation have but one purpose—
the maintenance of internal constancy.
Negative Feedback Loops
•When a particular measurement of the internal environment, such as a blood measurement, deviates
significantly from the normal range of values, it can be concluded that homeostasis is not being
maintained and that the person is sick.
•In order for internal constancy to be maintained, changes in the body must stimulate sensors that can
send information to an integrating center.
•This allows the integrating center to detect changes from a set point.
•In a similar manner, there is a set point for body temperature, blood glucose concentration, the tension
on a tendon, and so on.
•The integrating center is often a particular region of the brain or spinal cord, but it can also be a group of
cells in an endocrine gland.
•A number of different sensors may send information to a particular integrating center, which can then
integrate this information and direct the responses of effectors—generally, muscles or glands.
•The integrating center may cause increases or decreases in effector action to counter the deviations from
the set point and defend homeostasis.
•The thermostat of a house can serve as a simple example. Suppose you set the thermostat at a set point
of 70° F.
•If the temperature in the house rises sufficiently above the set point, a sensor connected to an integrating
center within the thermostat will detect that deviation and turn on the air conditioner (the effector in this
•The air conditioner will turn off when the room temperature falls and the thermostat no longer detects a
deviation from the set-point temperature.
•The effectors in the body are generally increased or decreased in activity, not just turned on or off.
•Because of this, negative feedback control in the body works far more efficiently than does a house
•For another example, if the blood glucose con- centration falls below normal, the effectors act to
increase the blood glucose.
•One can think of the effectors as “defending” the set points against deviations. Because the activity of
the effectors is influenced by the effects they produce, and because this regulation is in a negative, or
reverse, direction, this type of control system is known as a negative feedback loop
•After the air conditioner has been on for some time, the room temperature may fall significantly below
the set point of the thermostat.
•It is important to realize that these negative feedback loops are continuous, ongoing processes.
•Thus, a particular nerve fiber that is part of an effector mechanism may always display some activity,
and a particular hormone that is part of another effector mechanism may always be present in the blood.
•Changes from the normal range in either direction are thus compensated for by reverse changes in
•Homeostasis is best conceived as a state of dynamic constancy in which conditions are stabilized above
and below the set point.
•Control by antagonistic effectors is sometimes described as “push-pull,” where the increasing activity of
one effector is accompanied by decreasing activity of an antagonistic effector. This affords a finer degree
of control than could be achieved by simply switching one effector on and off.
•Normal body temperature is maintained about a set point of 37° C by the antagonistic effects of
sweating, shivering, and other mechanisms.
•Positive feedback—in this case, the action of effectors amplifies those changes that stimulated the
effectors. A thermostat that works by positive feedback, for example, would increase heat production in
response to a rise in temperature.
•It is clear that homeostasis must ultimately be maintained by negative rather than by positive feedback
•The effectiveness of some negative feedback loops, however, is increased by positive feedback
mechanisms that amplify the actions of a negative feedback response.
Neural and Endocrine Regulation
•Intrinsic, or “built into” the organs being regulated (such as molecules produced in the walls
of blood vessels that cause vessel dilation or constriction); and (2) those that are extrinsic, as in
regulation of an organ by the nervous and endocrine systems.
•Regulation by the endocrine system is achieved by the secretion of chemical regulators called hormones
into the blood, which carries the hormones to all organs in the body.
•Only specific organs can respond to a particular hormone, however; these are known as the target
organs of that hormone.
Feedback Control and Hormone Secretion
•Insulin, as previously described, produces a lowering of blood glucose.
•Because a rise in blood glucose stimulates insulin secretion, a lowering of blood glucose caused by
insulin’s action inhibits further insulin secretion.
•This closed-loop control system is called negative feedback inhibition
•The brain uses blood glucose as its primary source of energy—to entrust to the regulation of only one
Pp. 146 – 150
The Membrane Potential
•As a result of the permeability properties of the plasma membrane, the presence of non-diffusible