CONTROL OF BODY TEMPERATURE

& DISORDERS OF TEMPERATURE

REGULATION
Dr G.Gireesh,
PG Resident,
Dept .of Gen.Medicine
Sincere thanks Dr sujit,Dramit,Dr
salaah.
Normal Body Temperatures

Core Temperature
• The temperature of the deep tissues of the
body
• remains constant all the time, within ±1°F(±0.6°C)
• Altered when a person develops a febrile illness

.
Skin Temperature.
• The skin temperature, rises and falls with the
temperature of the surroundings.

Normal Core Temperature.

• The average normal core temperature is
generally considered to be between 98.0° and
98.6°F when measured orally and about 1°F
higher when measured rectally.
• During strenuous exercise, the temperature can
rise temporarily to as high as 101° to 104°F.

• When the body is exposed to extreme cold, the

temperature can often fall to values below 96°F.
• Normal mean oral temperature is 36.8° ± 0.4°C
(98.2° ± 0.7°F)
With low levels at 6 A.M. & higher levels at 4–6
P.M.
The maximum normal oral temperature is 37.2°C
(98.9°F) at 6 A.M. and 37.7°C (99.9°F) at 4 P.M.
• 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 37°C to 39°C).
• Fever : temperature of >37.2°C (>98.9°F) am or a
temperature of >37.7°C (>99.9°F) pm
 Heat Production
(1) Basal rate of metabolism of all the cells of the
body
(2) Extra rate of metabolism caused by muscle
activity
(3) Extra metabolism caused by the effect of
thyroxine and, to a less extent, other hormones,
such as growth hormone and testosterone on the
cells
(4) Extra metabolism caused by the effect of
epinephrine, nor-epinephrine, and sympathetic
stimulation on the cells
(5) Extra metabolism caused by increased chemical
activity in cells
(6) Thermogenic effect of food.
Heat Loss
 Sweating and its regulation
• Stimulation of the anterior hypothalamus-preoptic
area in the brain either electrically or by excess
heat causes sweating.
• Ant. hypothalamus Spinal cord
aut.path symp.fl

Skin
Mechanism of sweating and the role of aldosterone..
Rate of flow of sweat and
its concentration depend
on the amount of
stimulation of the sweat
gland.

Unacclimatised persons
tend to lose more salts
in their sweat.

Later the action of the

aldosterone decreases
the amount of the salt.
Regulation of Body Temperature—Role of the
Hypothalamus
• It occurs by nervous feedback mechanisms
• These operate through temperature-regulating
centers located in the hypothalamus.
• Temperature detectors play a major role
• Preoptic and anterior hypothalamic nuclei of the
hypothalamus are the centres for this action
• The anterior hypothalamic-preoptic area

Heat sensitive neurons Cold sensitive neurons

Fire when temp ses Fire when temp ses

Posterior Hypothalamus Integrates the Central
and Peripheral Temperature Sensory Signals

Body response to cold

• 1. Skin vasoconstriction throughout the body.
• 2. Piloerection.
• 3. Increase in thermogenesis (heat production).

Dorsomedial portion of the posterior hypothalamus

near the wall of the third ventricle is an area called
the primary motor center for shivering.
During maximum shivering, body heat production
can rise to four to five times normal.
Concept of a “Set-Point” for Temperature
Control

Critical body core temperature of about 37.1°C (98.8 0F),

This crucial temperature level is called the “set-point” of
the temperature control mechanism.
That is, all the temperature control mechanisms
continually attempt to bring the body temperature
back to this set-point level.
Skin Temperature can slightly alter the Set-Point for
Core Temperature Control
FACTORS PREDISPOSING TO COLD INJURY
INDIVIDUAL FACTORS
Inadequate clothing and shelter
Lean and low body fat
Low physical fitness
Advanced age
Young children
Black men and women
MEDICATIONS
Alcohol
Anesthetics
Antidepressants
Antithyroid agents
Sedatives and narcotics
• HEALTH CONDITIONS

Burns
Diabetes
Hypoglycemia
Neurologic lesions
Dementia
Hypoadrenalism,
Hypopituitarism,
Hypothyroidism
Raynaud's phenomenon
Sickle cell trait
Trauma
Spinal cord injury
 ENVIRONMENTAL FACTORS

• Cold temperatures
• High air motion
• Rain and immersion
• Skin contact with metal and fuels
• Repeated cold exposure
• Physical fatigue
• Immobility
• High-altitude and low–oxygen tension environments
HYPOTHERMIA: STAGES AND ASSOCIATED
CLINICAL MANIFESTATIONS
FROST BITE
Peripheral cold injuries include both freezing and
nonfreezing injuries to tissue.
PREDISPOSING FACTORS
metal or volatile solutions.
constrictive clothing or boots,
immobility,
vasoconstrictive medications.
Frostbite occurs when the tissue temperature drops
below 0°C. Ice crystal formation subsequently
distorts and destroys the cellular architecture. Once
the vascular endothelium is damaged, stasis
progresses rapidly to microvascular thrombosis.
After the tissue thaws, there is progressive dermal
ischemia.
Finally, thrombosis, ischemia, and superficial necrosis
appear.
The development of mummification and demarcation
may take weeks to months.

CLINICAL PRESENTATION
The initial presentation can be deceptively benign.
The symptoms include a sensory deficiency affecting
light touch, pain, and temperature perception.
The acral areas and distal extremities are the most
common insensate areas.
• Deep frostbitten tissue appears waxy, mottled, yellow,
or violaceous-white.
• Presenting signs include warmth or sensation with
normal color.
• Injury is superficial if the subcutaneous tissue is pliable
or dermis can be rolled over boney prominences.
• Can be classified as superficial or deep. Superficial
does not entail tissue loss, retrospectively graded like
a burn.
• First-degree frostbite causes only anesthesia and
erythema.
• Second degree: superficial vesiculation surrounded by
edema and erythema
• Third-degree:hemorrhagic vesicles reflect a serious
injury to the microvasculature and indicate.
• Fourth-degree injuries damage subcuticular, muscular,
and osseous tissues.
 FEVER AND HYPERTHERMIA
• Elevation of the Hypothalamic Set Point by Cytokines
• During fever, 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.

• Pyrogenic cytokines such as IL-1, IL-6, and TNF are

released from the cells and enter the systemic circulation.
Although the systemic effects of these circulating cytokines
lead to fever by inducing the synthesis of PGE2, they also
induce PGE2 in peripheral tissues.causing the nonspecific
myalgias and arthralgias that often accompany fever

• it is the elevation of PGE2 in the brain that starts the

process of raising the hypothalamic set point for core
temperature.
• As hypothalamic set point ,neurons in the
vasomotor center are activated and
vasoconstriction commences, due to which the
individual first notices vasoconstriction in the hands
and feet.
• Shunting of blood away from the periphery to the
internal organs essentially decreases heat loss from
the skin, and the person feels cold. For most fevers,
body temperature increases by 1°–2°C.
• Shivering, which increases heat production from the
muscles, may begin at this time,but shivering is not
required if heat conservation mechanisms raise
blood temperature sufficiently. Nonshivering heat
production from the liver also contributes to
increasing core temperature
• The mechanisms for heat conservation continue
until the temperature of the blood bathing the
hypothalamic neurons matches the new
thermostat setting. Once that point is reached,
the hypothalamus maintains the temperature at
the febrile level by the same mechanisms of heat
balance that function in the afebrile state.
• When the hypothalamic set point is again reset
downward (in response to either a reduction in
the concentration of pyrogens or the use of
antipyretics), the processes of heat loss through
vasodilation and sweating are initiated. Loss of
heat by sweating and vasodilation continues until
the blood temperature at the hypothalamic level
matches the lower setting
• Hyperpyrexia-A fever of >41.5°C (>106.7°F)
extraordinarily high fever
Develops in patients with severe infections,
commonly occurs in patients with CNS hemorrhages
• Hypothalamic fever - elevated temperature caused
by abnormal hypothalamic function due to local
trauma, hemorrhage, tumor, or intrinsic
hypothalamic malfunction.
• Hyperthermia is characterized by an uncontrolled
increase in body temperature that exceeds the
body's ability to lose heat.
Results from1.Exogenous heat exposure
2.Endogenous heat
production
• Dangerous as compensatory mechanisms can’t
cope up.
 CAUSES OF HYPERTHERMIA SYNDROMES
• Heat Stroke :
Exertional: Exercise in higher than normal in heat and/or
humidity Nonexertional: Anticholinergics, including antihistamines;
antiparkinsonian drugs; diuretics; phenothiazines
• Drug-Induced Hyperthermia Amphetamines, cocaine,
phencyclidine (PCP), methylenedioxymethamphetamine (MDMA),
salicylates, lithium, anticholinergics, sympathomimetics
• Neuroleptic Malignant Syndrome Phenothiazines;
butyrophenones, including haloperidol, bromperidol; fluoxetine;
loxapine; metoclopramide;
• Serotonin Syndrome Selective serotonin reuptake inhibitors
(SSRIs), monoamine oxidase inhibitors (MAOIs), tricyclic
antidepressants
• Malignant Hyperthermia Inhalational anesthetics,
succinylcholine
• Endocrinopathy Thyrotoxicosis, pheochromocytoma
• Central Nervous System Damage Cerebral hemorrhage, status
epilepticus, hypothalamic injury
• Heat stroke can be1.exertional 2.nonexertional.
• Exertional heat stroke typically occurs in
individuals exercising at elevated ambient
temperatures and/or humidities. In a dry
environment and at maximal efficiency, sweating
can dissipate ~600 kcal/h, requiring the
production of >1 L of sweat in healthy individuals,
dehydration or the use of medications (e.g., over-
the-counter antihistamines with anticholinergic
side effects) may precipitate exertional heat
stroke.
• Non-exertional heat stroke typically occurs in
either very young or elderly individuals,
particularly during heat waves
• Drug-induced hyperthermiacommon with the
increased use of prescription psychotropic drugs
and illicit drugs. Drug-induced hyperthermia may
be caused by (MAOIs),TCA’S, amphetamines,
phencyclidine (PCP), LSD,
methylenedioxymethamphetamine
• Malignant hyperthermia
Fatal Condn.,occurs in individuals with an
inherited abnormality of skeletal-muscle
sarcoplasmic reticulum that causes a rapid
increase in intracellular calcium levels in
response to halothane and other inhalational
anesthetics or to succinylcholine. Elevated
temperature, increased muscle metabolism,
muscle rigidity, rhabdomyolysis, acidosis, and
cardiovascular instability develop within minutes..
• The neuroleptic malignant syndrome
Caused by the inhibition of central dopamine
receptors in the hypothalamus,
Seen as increased heat generation and
decreased heat dissipation and is characterized by
"lead-pipe" muscle rigidity, extrapyramidal side
effects, autonomic dysregulation, and hyperthermia.
occurs in the setting of neuroleptic agent use
(antipsychotic phenothiazines, haloperidol,
prochlorperazine, metoclopramide) or the withdrawal
of dopaminergic drugs
• The serotonin syndrome, seen with (SSRIs), MAOIs,
and other serotonergic medications, has many
overlapping features, including hyperthermia, but
distinguished by the presence of diarrhea, tremor,
and myoclonus and absence of the lead-pipe rigidity
 Pathogenesis of Fever
• Pyrogen is a any substance that causes fever.
• Exogenous pyrogens are derived from outside
the patient; most are microbial products, microbial
toxins, or whole microorganisms. E.g-
lipopolysaccharide (endotoxin) produced by all
gram-negative bacteria.
• Pyrogenic products of gram-positive organisms
include the enterotoxins of Staphylococcus
aureus and the group A and B streptococcal
toxins, also called superantigens. One
staphylococcal toxin of clinical importance is of S.
aureus from patients with toxic shock syndrome.
• Pyrogenic Cytokines
• Cytokines are small proteins (molecular mass,
10,000–20,000 Da) that regulate immune,
inflammatory, and hematopoietic processes
• Each cytokine is encoded by a separate gene,
and each pyrogenic cytokine has been shown to
cause fever in laboratory animals and in humans
• The pyrogenic cytokines include IL-1, IL-6, tumor
necrosis factor (TNF), ciliary neurotropic factor
(CNTF), and interferon (IFN)
• There are four receptors for PGE2, and each signals the
cell in different ways. Of the four receptors, the third
(EP-3) is essential for fever
• Release of PGE2 from the brain side of the hypothalamic
endothelium triggers the PGE2 receptor on glial cells,
and this stimulation results in the rapid release of cyclic
adenosine 5'-monophosphate (cyclic AMP), which is a
neurotransmitter, the release of cyclic AMP from the glial
cells activates neuronal endings from the
thermoregulatory center that extend into the area. The
elevation of cyclic AMP is thought to account for
changes in the hypothalamic set point either directly or
indirectly (by inducing the release of neurotransmitters).
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. The direct activation of Toll-like receptors also
results in PGE2 production and fever.
Approach to Fever
 MECHANISMS OF ANTIPYRETIC AGENTS
• THE REDUCTION OF FEVER BY lowering of the elevated
hypothalamic set point is a direct function of reducing the level
of PGE2 in the thermoregulatory center.
• The synthesis of PGE2 depends on the constitutively
expressed enzyme cyclooxygenase. The substrate for
cyclooxygenase is arachidonic acid released from the cell
membrane, and this release is the rate-limiting step in the
synthesis of PGE2. Therefore, inhibitors of cyclooxygenase
are potent antipyretics. The antipyretic potency of various
drugs is directly correlated with the inhibition of brain
cyclooxygenase. Acetaminophen is a poor cyclooxygenase
inhibitor in peripheral tissue and lacks anti-inflammatory
activity; in the brain
• acetaminophen is oxidized by the p450 cytochrome system,
and the oxidized form inhibits cyclooxygenase activity.
• Oral aspirin and acetaminophen are equally
effective in reducing fever. Nonsteroidal anti-
inflammatory drugs (NSAIDs) such as ibuprofen
and COX-2 inhibitors are also excellent
antipyretics.
• Glucocorticoids :act at two levels. First, similar to
the cyclooxygenase inhibitors, glucocorticoids
reduce PGE2 synthesis by inhibiting the activity of
phospholipase A2, which is needed to release
arachidonic acid from the cell membrane.
Second, glucocorticoids block the transcription of
the mRNA for the pyrogenic cytokines.
 TREATMENT OF FEVER
• The objectives in treating fever are first to reduce
the elevated hypothalamic set point and second
to facilitate heat loss. Reducing fever with
antipyretics also reduces systemic symptoms of
headache, myalgias, and arthralgias.
• Oral aspirin and NSAIDs effectively reduce fever
but can adversely affect platelets and the
gastrointestinal tract. so acetaminophen is
preferred . In children, acetaminophen must be
used because aspirin increases the risk of Reye's
syndrome. If the patient cannot take oral
antipyretics, parenteral preparations of
NSAIDs,rectal suppository preparations of can be
used.
• In hyperpyrexia, the use of cooling blankets facilitates the
reduction of temperature; however, cooling blankets should
not be used without oral antipyretics
• Hyperthermia

• A high core temperature in a patient with an appropriate

history (e.g., environmental heat exposure or treatment with
anticholinergic or neuroleptic drugs, tricyclic, succinylcholine,
or halothane) along with appropriate clinical findings (dry skin,
hallucinations, delirium, pupil dilation, muscle rigidity, and/or
elevated levels of creatine phosphokinase) suggests
hyperthermia

• Physical cooling with sponging, fans, cooling blankets, and ice

baths should be initiated immediately in conjunction with IV
fluids and appropriate pharmacologic agents. If insufficient
cooling is achieved by external means, internal cooling can be
achieved by gastric or peritoneal lavage with iced saline
• In extreme circumstances, hemodialysis or even
cardiopulmonary bypass with cooling of blood performed.

• Malignant hyperthermia : treated with cessation of

anesthesia and IV administration of dantrolene sodium (1–2.5
mg/kg 6 h) for at least 24–48 h—until oral dantrolene can be
administered .
• Procainamide should also be administered to patients with
malignant hyperthermia because of the likelihood of
ventricular fibrillation in this syndrome.

• Neuroleptic malignant syndrome : RX with Dantrolene

• The neuroleptic malignant syndrome may also be treated with
bromocriptine, levodopa, amantadine, or nifedipine or by
induction of muscle paralysis with curare and pancuronium.
• drug-induced hyperthermia &hyperthermia of the serotonin
syndrome – both treated with dantrolene