C h a p t e r 3
Inflammation, the Inflammatory Response, and Fever
63
for energy. The rise in fibrinogen causes red blood cells
to form stacks (rouleaux) that settle or sediment more
rapidly than individual erythrocytes. This is the basis
for the accelerated erythrocyte sedimentation rate (ESR)
that occurs in disease conditions characterized by the
systemic inflammatory response.
White Blood Cell Response
Leukocytosis
, or the increase in white blood cells, is a fre-
quent sign of an inflammatory response, especially those
caused by bacterial infection. In acute inflammatory condi-
tions, the white blood cell count commonly increases from
a normal value of 4000 to 10,000 cells/
μ
L to 15,000 to
20,000 cells/
μ
L. After being released from the bone mar-
row, circulating neutrophils have a life span of only about
10 hours and therefore must be constantly replaced if their
numbers are to be adequate. With excessive demand for
phagocytes, immature forms of neutrophils (bands) are
released from the bone marrow. The phrase “a shift to the
left” in a white blood cell differential count refers to the
increase in immature neutrophils seen in severe infections.
Bacterial infections produce a relatively selective
increase in neutrophils (neutrophilia), while parasitic
and allergic responses induce eosinophilia. Viral infec-
tions tend to produce a decrease in neutrophils (neutro-
penia) and an increase in lymphocytes (lymphocytosis).
3
A decrease in white blood cells (leukopenia) may also
occur in persons with overwhelming infections or
impaired ability to produce white blood cells.
Systemic Inflammatory Response
In severe bacterial infections (sepsis), the large quantities
of microorganisms in the blood result in an uncontrolled
inflammatory response with the production and release
of enormous quantities of inflammatory cytokines (most
notably IL-1 and TNF-
α
) and development of what is
referred to as the
systemic inflammatory response syn-
drome
(see Chapter 20).
30
A decrease in total white
blood cells (leukopenia) may occur in persons with
overwhelming infections or impaired ability to produce
white blood cells.
Fever
Fever (pyrexia) is an elevation in body temperature
caused by an upward displacement of the set point of
the thermoregulatory center in the hypothalamus.
31–33
It is one of the most prominent manifestations of the
acute-phase response.
1,2
BodyTemperature Regulation
The temperature in the deep tissues of the body (core
temperature) is normally maintained within a range
of 36.0°C to 37.5°C (97.0°F to 99.5°F).
31,32
Within
this range, there are individual differences and diurnal
variations; internal core temperatures reach their high-
est point in late afternoon and evening and their lowest
point in the early morning hours (Fig. 3-7). Virtually
all biochemical processes in the body are affected by
changes in temperature. Metabolic processes speed up
or slow down depending on whether body temperature
is rising or falling.
Body temperature, which reflects the difference
between heat production and heat loss, is regulated by
the
thermoregulatory center
in the hypothalamus. Body
heat is generated in the tissues of the body, transferred to
the skin surface by the blood, and then released into the
environment surrounding the body. The thermoregula-
tory center regulates the temperature of the deep body
tissues, or “core” of the body, rather than the surface
temperature. It does so by integrating input from cold
and warmth receptors located throughout the body and
participating in negative feedback mechanisms.
The
thermostatic set point
of the thermoregulatory
center is the level at which body temperature is regu-
lated so that core temperature is maintained within
the normal range. When body temperature begins to
rise above this set point, heat-dissipating behaviors are
initiated, and when the temperature falls below the set
point, heat production is increased. A core temperature
greater than 41°C (105.8°F) or less than 34°C (93.2°F)
usually indicates that the body’s thermoregulatory abil-
ity is impaired (Fig. 3-8). Body responses that produce,
conserve, and dissipate heat are described in Table 3-1.
Spinal cord injuries that transect the cord at T6 or above
can seriously impair temperature regulation because the
hypothalamus no longer can control skin blood flow or
sweating.
In addition to physiologic thermoregulatory mecha-
nisms, humans engage in voluntary behaviors to help
regulate body temperature. These behaviors include the
selection of proper clothing and regulation of environ-
mental temperature through heating systems and air
conditioning. Body positions that hold the extremities
close to the body (e.g., huddling) prevent heat loss and
are commonly assumed in cold weather.
Mechanisms of Heat Production.
Metabolism is the
body’s main source of heat production. The sympathetic
neurotransmitters epinephrine and norepinephrine,
which are released when an increase in body temperature
is needed, act at the cellular level to shift body metabo-
lism to heat production rather than energy generation.
This may be one of the reasons fever tends to produce
feelings of weakness and fatigue. Thyroid hormone
38
37
36
35
6
AM
Noon
6
PM
Midnight
6
AM
Time
Rectal temperature
°
C
FIGURE 3-7.
Normal diurnal variations in body temperature.
