FEVER

Body temperature is controlled by the thermoregulatory center of the

hypothalamus
Hypothalamus receive two kinds of signals: one from peripheral nerves that
transmit information from warmth/cold receptors in the skin and the other
from the temperature of the blood bathing the region.
In a neutral temperature environment, the human metabolic rate produces
more heat than is necessary to maintain the core body temperature in the
range of 36.537.5C (97.799.5F).
A normal body temperature is maintained despite environmental variations
because the hypothalamic thermoregulatory center balances the excess heat
production derived from metabolic activity in muscle and the liver with heat
dissipation from the skin and lungs.
The maximal normal oral temperature is 37.2C (98.9F) at 6 a.m. and 37.7C
(99.9F) at 4 p.m an a.m. temperature of >37.2C (>98.9F) or a p.m.
temperature of >37.7C (>99.9F) would define a fever. The normal daily
temperature variation is typically 0.5C (0.9F).
Rectal temperatures are generally 0.4C (0.7F) higher than oral readings
The lower oral readings are probably attributable to mouth breathing, which is
a factor in patients with respiratory infections and rapid breathing.
Lower-esophageal temperatures closely reflect core temperature.
Fever is an elevation of body temperature that exceeds the normal daily
variation and occurs in conjunction with an increase in the hypothalamic set
point (e.g., from 37C to 39C)
PATHOGENESIS OF FEVER

PYROGENS
pyrogen : any substance that causes fever.
Exogenous pyrogens : derived from outside the patient; most are microbial
products, microbial toxins, or whole microorganisms (including viruses). Ex
: lipopolysaccharide (endotoxin) produced by all gram-negative bacteria,
pyrogenic products of gram-positive organisms include the enterotoxins of
Staphylococcus aureus and the groups A and B streptococcal toxins.
Endogenous pyrogens (pyrogenic cytokines) : small proteins that regulate
immune, inflammatory, and hematopoietic processes. Ex : IL-1, IL-6, tumor
necrosis factor (TNF), ciliary neurotropic factor(a member of the IL-6
family), and Interferons (IFNs) particularly IFN-.
A wide spectrum of bacterial and fungal products induce the synthesis
and release of pyrogenic cytokines trigger the hypothalamus to raise
the set point to febrile levels.
ELEVATION OF THE HYPOTHALAMIC SET POINT BY CYTOKINES
Myeloid and endothelial cells are the primary cell types that produce
pyrogenic cytokines.
Pyrogenic cytokines such as IL-1, IL-6, and TNF are released from these cells
and enter the systemic circulation.
Circulating cytokines lead to fever by inducing the synthesis of PGE2, some
systemic PGE2 escapes destruction by the lung and gains access to the
hypothalamus via the internal carotid. Elevation of PGE2 in the brain starts the
process of raising the hypothalamic set point for core temperature.
During fever, levels of prostaglandin E2 (PGE2) are elevated in hypothalamic
tissue and the third cerebral ventricle. The concentrations of PGE2 are highest

near the circumventricular vascular organs (organum vasculosum of lamina

terminalis)networks of enlarged capillaries surrounding the hypothalamic
regulatory centers.
The release of PGE2 from the brain side of the hypothalamic endothelium
triggers the PGE2 receptor on glial cells release of cyclic adenosine 5monophosphate (cAMP) activates neuronal endings from the
thermoregulatory center changes in the hypothalamic set point.
Cytokines also induce PGE2 in peripheral tissues. The increase in PGE2 in the
periphery accounts for the nonspecific myalgias and arthralgias that often
accompany fever.
Distinct receptors for microbial products are located on the hypothalamic
endothelium. These receptors are called Toll-like receptors and are similar in
many ways to IL-1 receptors. IL-1 receptors and Toll-like receptors share the
same signal transducing mechanism. Thus, the direct activation of Toll-like
receptors or IL-1 receptors results in PGE2 production and fever.

Fever Pattern

Intermitten fever : one in which temperature rises and fall, returns to

normal at least once every 24hours. usually normal or low in the morning
and peaking between 4:00 and 8:00 P.M.This group includes fever due to
localized pyogenic infections and bacterial endocarditis; chills and
leukocytosis are usually present. Malaria (commonly with leukopenia) may
present as quotidian (daily spike),tertian (spike every third day), or
quartan (spike every fourthday) types.
Remitten fever : the temperature does not return to normal and varies a
few degrees in either direction, the fluctuation is more than 1C.
Associated with viral upper respiratory tract, Legionella, and mycoplasma
infection.
Sustained or continous fever : the temperature is elevated all the time but
the difference between the maximum and minimum does not exceed 1C.
Within this group fall fevers due to lobar and gram-negative pneumonia,
the rickettsioses, typhoid fever, CNS disorders, tularemia, and falciparum
(malignant tertian) malaria

Recurrent or relapsing fever : one or more episodes of fever, each as long

as several days, with one or more days of normal temperature between
episodes.
Saddle-back (biphasic) fever: several days of fever, a distinct reduction in
febrile levels for1 day, and then several additional days of higher
fever.This type of fever pattern is typical of dengue and yellow fever,
Colorado tick fever, relapsing fever, Rift Valley fever, influenza, and other
viral infections such as poliomyelitis and lymphocytic choriomeningitis.