I.M.
Harry Series
By DeeEtch2021
Chapter 15: Fever
Body temperature is controlled by:
2 sources of signals related to
temperature:
In the neutral temperature
environment, the human metabolic
rate produces MORE heat than
necessary
Excess heat production from:
1. Muscle (shivering)
2. Liver (nonshivering)
Mean oral temperature is:
The normal daily temperature
variation is:
During menstrual cycle
Rectal temperature are generally
higher than oral temp by:
This closely reflect core temperature:
Unadjusted-mode tympanic
membrane temperature (measures
radiant heat from ear canal) are
lower than rectal temperatures by:
Definition of Fever
For most fevers, body temperature
increases by
Behavioral adjustments help raise
body temperature by:
A fever of > 41.5*C is called
Hypothalamus
1. Peripheral nerves (warm and cold receptor in skin)
2. Blood bathing the neurons of hypothalamus
To maintain the core body temperature of:
36.5 – 37.5 *C
(97.7 – 99.5 *F)
Heat dissipation from:
1. Skin
2. Lungs
Heat conservation from:
Vasoconstriction (shunt blood away from periphery)
36.8*C +/- 0.4 *C
LOW levels at 6 AM (>37.2 would define a fever)
HIGH levels at 4-6 PM (>37.7 would define a fever)
Typically 0.5 *C
Called Circassian rhythm
Can be increased to as great as 1*C during recovery
from febrile illness
Fixed in early childhood.
Elderly has REDUCED ability to develop fever.
AM temperature generally lower during the 2 weeks
before ovulation
Rises by ~0.6*C with ovulation until menses
0.4 *C
Lower-esophageal temperature
0.8 * C
Elevation of body temperature that exceeds the normal
daily variation and occurs in conjunction with an
increase in the hypothalamus set point (thermostat)
1-2 *C
Decreasing heat loss
Eg. Putting more clothing
Hyperpyrexia
Hyperpyrexia MOST commonly
occurs in patient with:
Term used to describe elevated
temperature caused by abnormal
hypothalamic function
Characterized by an uncontrolled
increase in body temperature that
exceeds the body’s ability to lose
heat
2 mechanisms by which
hyperthermia can result
CNS hemorrhage
(Also seen in severe infection)
Hypothalamic fever
(However, most patients with hypothalamic damage
have SUBnormal, not supranormal, body temperature
Hyperthermia
(Heat stroke)
-this does not involve pyrogenic molecule (compared to
fever)
-exceeds thermostat
1. Exogenous heat exposure
2. Endogenous heat production

(Eg. Work or exercise in hot environment)

Hyperthermia is diagnosed on the The events immediately preceding the elevation of core
basis of temperature
Skin In heat stroke syndrome: Skin in fever:
Hot and dry Can be cold due to vasoconstriction
Antipyretic in hyperthermia: Antipyretic in fever:
Not effective Adequate doses of either aspirin or acetaminophen
result in some decrease in body temperature
Pathogenesis of fever
Any substance that causes fever Pyrogen
Exogenous pyrogens -microbial products
-microbial toxins
-whole microorganism

(Eg. In gram negative: Lipopolysaccharide (endotoxins),

enterotoxin of staph. Aureaus, superantigens on strep
A and B)
A dose of 2-3 mg/kg endotoxins -fever
produces -leukocytosis
-acute-phase reactants
-generalized symptom of malaise
Small protein that regulate immune, Cytokines
inflammatory, and hematopoietic
processes
Pyrogenic cytokines IL-1
(Prev. Endogenous pyrogens) IL-6
Tumor Necrosis Factor (TNF)
Ciliary neutropic factors
Fever is a prominent side effect of True
interferon alfa therapy
A dose of 1-10 ng/kg of IL-6 is True
required for fever production
During fever, levels of _____ are Prostaglandin E2
elevated in hypothalamic tissue and
third ventricle. (Concentration highest near circumventricular vascular
(Synthesis induced by cytokines) organs: organum vasculosum of lamina terminalis:
networks of enlarged capillaries surrounding
hypothalamic regulatory centers)
First step in raising set point to Interaction of exogenous pyrogens and pyrogenic
febrile levels/initiating fever cytokines with endothelium of the organum
vasculosum
See figure 15-1
Primary cell types that produce Myeloid and endothelial cells
pyrogenic cytokines
This accounts for the nonspecific Increase PGE2 in the periphery
myalgia and arthralgias that
accompany fever
There are 4 receptors for PGE2, but Third receptor (EP-3)
most essential for fever is:
Although PGE2 is essential fever, it is True
NOT a neurotransmitter
Release of PGE2 from brain side of hypothalamic endothelium -> trigger receptor on glial cells -
> rapid release of cAMP (a neurotransmitter) -> activates neuronal endings from
thermoregulatory center
Receptor for microbial products in Toll-like receptors
hypothalamic endothelium
(Similar to IL-1 receptor)
Cytokines produced in the brain may True
account for the hyperpyrexia of CNS
hemorrhage, trauma, or infection
Approach to Fever
Blunted febrile responses are seen Newborns, elderly, chronic hepatic or renal failure,
in: glucocorticoids treatment, anti cytokines treatment
Measurement of circulating True
cytokines in patient with fever is NOT
helpful
In patient with low-grade fever or CRP
suspected occult disease, the most ESR
valuable measurements are:
Patient receiving long-term Because of lowered host defenses
treatment with anti cytosine-based
regimen are at increased risk of (Eg. Chron’s disease, rheumatoid arthritis, psoriasis)
infection
Most Fever are associated with self- True
limited infections
Treatment of fever and it’s symptom True
with routine antipyretic does NO
harm and does NOT slow resolution
of common viral and bacterial
infections
In bacterial infections, withholding of In evaluating the effectiveness of particular antibiotics,
antipyretic therapy can be helpful: esp. in the absence of a positive culture
Temperature-pulse dissociation Relative Bradycardia

(Seen in typhoid fever, brucellosis, leptospirosis, drug-

induced fever, factitious fever)
Characteristic Fever pattern of
plasmodium Vivax
Characteristic Fever pattern of
plasmodium Malariae
Characteristic Fever pattern of
Borrelia infection
Pel-Einstein pattern
(Classic for Hodgkin disease and
other lymphoma)
Characteristic Fever pattern of cyclic
neutropenia
Recurrent fever is characteristic of
The reduction of Fever by lowering
of the elevated hypothalamic set
point is a direct function of:
Rate limiting step in the synthesis of
PGE2
The antipyretic potency of various
drugs is directly correlated with
Acetaminophen
Oral Aspirin and Acetaminophen are
equally effective in reducing fever in
humans
Chronic, high dose therapy with
antipyretic does NOT reduce normal
core temperature
Glucocorticoids acts at two level
NSAIDs that reduce IL-1-induced IL-6
production
Objectives of treating fever
Acetaminophen is preferred as
antipyretic
Fever increases demand for oxygen
In hyperpyrexia
Fever every third day
Fever every fourth day
Days of fever followed by several days of afebrile
period then relapse into additional days of fever
Fever lasting 3-10 days followed by 3-10 days afebrile
Fever occurs every 21 days
(Accompanies the neutropenia)
Auto inflammatory disease
(Eg. Adult and juvenile still’s disease, familial
Mediterranean fever, hyper-IgD syndrome, idiopathic
pericarditis, gouty arthritis)
(See table 15-1)
Note: also has neutrophilia and serosal inflammation
Note: Fever is reduced by blocking IL-1 activity with
Anakinra or canakinumab
Reduction of the PGE2 level in the thermoregulatory
center
Release of arachidonic acid from cell membrane
The inhibition of brain cyclooxygenase
Poor COX inhibitor in peripheral tissue
In the brain, it is oxidized by p450 cytochrome system,
and the oxidized form inhibit COX activity
Also inhibit COX-3 (which is found only in CNS)
TRUE
PGE2 plays NO role in normal thermoregulation
-inhibits phospholipids A2
-blocks transcription of the mRNA for pyrogenic
cytokines
Ibuprofen and Cox-2 inhibitors
-reduce the elevated hypothalamic set point
-facilitate heat loss
Because oral aspirin and NSAIDS (while equally
effective), adversely affects platelet and GI tract
For every increase of 1*C over 37 *C, there is 13%
increase in oxygen consumption
Use of cooling blankets ( on top of antipyretic)
In CNS bleeding/ trauma Reduced core temperature mitigates the detrimental
effects of high temperature on the brain