Chapter 1
Feedback Systems
The thermoregulatory system just described is an example of a
negative feedback
system, in which 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. Thus, in our example,
a decrease in body temperature led to responses that tended
to increase the body temperature—that is, move it toward its
original value.
Without negative feedback, oscillations like some of
those described in this chapter would be much greater, and
therefore the variability in a given system would increase.
Negative feedback also prevents the compensatory responses
to a loss of homeostasis from continuing unabated. Details
of the mechanisms and characteristics of negative feedback
within different systems will be addressed in later chapters.
For now, it is important to recognize that negative feedback
plays a vital part in the checks and balances on most physi-
ological variables.
Negative feedback may occur at the organ, cellular, or
molecular level. For instance, negative feedback regulates
many enzymatic processes, as shown in schematic form in
Figure 1–5
. An enzyme is a protein that catalyzes chemical
reactions (Chapter 3). In this example, the product formed
from a substrate by an enzyme negatively feeds back to inhibit
further action of the enzyme. This may occur by several pro-
cesses, such as chemical modifi
cation of the enzyme by the
product of the reaction. The production of energy within cells
is a good example of a chemical process regulated by feedback.
When a cell’s energy stores are depleted, glucose molecules are
enzymatically broken down to provide chemical energy that
is stored in adenosine triphosphate (ATP). As ATP accumu-
lates in the cell, it inhibits the activity of some of the enzymes
involved in the breakdown of glucose. Thus, as ATP levels
increase within a cell, further production of ATP slows down
due to negative feedback. Conversely, when ATP levels drop
within a cell, negative feedback is removed, and more glucose
is broken down so that more ATP can be produced.
As an aside, not all forms of feedback are negative. In
some cases,
positive feedback
accelerates a process, leading
to an “explosive” system. This is counter to the principle of
homeostasis, because positive feedback has no obvious means
of stopping. Not surprisingly, therefore, positive feedback is
less common in nature than negative feedback. Nonetheless,
there are examples in physiology where positive feedback is very
important. One well-described example, which you will learn
about in Chapter 17, is the process of parturition (birth). As
the uterine muscles contract and a baby is forced through the
birth canal during labor, signals are relayed via nerves to the
brain. This initiates the secretion into the blood of a molecule
called oxytocin, which is a potent stimulator of further uterine
contractions. As the uterus contracts ever harder in response to
oxytocin, more stretch occurs, and more signals are sent to the
brain, resulting in yet more oxytocin secretion. This self-per-
petuating cycle continues until fi nally the baby is born.
Resetting of Set Points
As we have seen, changes in the external environment can dis-
place a variable from its set point. In addition, the set points for
many regulated variables can be physiologically reset to a new
value. A common example is fever, the increase in body tem-
perature that occurs in response to infection and that is some-
what analogous to raising the setting of a home’s thermostat.
The homeostatic control systems regulating body temperature
are still functioning during a fever, but they maintain the tem-
perature at a higher value. This regulated rise in body tem-
perature is adaptive for fi ghting the infection, because elevated
temperature inhibits proliferation of some pathogens. In fact,
this is why a fever is often preceded by chills and shivering.
The set point for body temperature has been reset to a higher
value, and the body responds by shivering to generate heat.
The fact that set points can be reset adaptively, as in
the case of fever, raises important challenges for medicine,
as another example illustrates. Plasma iron concentration
decreases signifi cantly during many infections. Until recently,
it was assumed that this decrease was a symptom caused by
the infectious organism and that it should be treated with iron
supplements. In fact, just the opposite is true. The decrease
in iron is brought about by the body’s defense mechanisms
and serves to deprive the infectious organisms of the iron they
require to replicate. Several controlled studies have shown that
iron replacement can make the illness much worse. Clearly it is
crucial to distinguish between those deviations of homeostati-
cally controlled variables that are truly part of a disease and
those that, through resetting, are part of the body’s defenses
against the disease.
The examples of fever and plasma iron concentration
may have left the impression that set points are reset only in
response to external stimuli, such as the presence of bacteria,
but this is not the case. Indeed, the set points for many reg-
ulated variables change on a rhythmical basis every day. For
example, the set point for body temperature is higher during
the day than at night.
Inactive intermediate 2
Active product
Inactive intermediate 1
Enzyme A
Enzyme B
Enzyme C
Figure 1–5
Hypothetical example of negative feedback (as denoted by the
circled minus sign and dashed feedback line) occurring within a set
of sequential chemical reactions. By inhibiting the activity of the
fi rst enzyme involved in the formation of a product, the product can
regulate the rate of its own formation.
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