Thermoregulation,
Fever,
Hyperthermia,
Hypothermia
Dariusz Nowak

Body temperature

Normal oral temperature 37°C (98.6 ºF)
Healthy individuals (18-40 yrs) – 36.8±0.4ºC (98.2±0.7°F)
Nadir at 6a.m. , zenith at 4 to 6 p.m. ,Δ 0.5- 1ºC
Oral temperature max 37.2º C at 6 a.m. , max 37.7º C at 4

p.m.

Fever definition ; > 37.2 ºC , 37.7 ºC

Rectal temperature – higher by 0.6 ºC
esophageal (lower part) temperature,
Temperature of freshly passed urine specimen

Thermoregulation and

body temperature

Fever – elevation of body temperature above the circadian

range as the result of change of the thermoregulatory

center (anterior hypothalamus)

Hyperthermia – increase in the body temperature above the

hypothalamic set point due to insufficient heat

dissipation

Hypothermia – core body temperature < 35 °C

Mild 35 – 32 °C
Moderate 32-28 °C
Severe <28 °C

Body temperature

24 hr circadian temperature rhythm
Healthy subjects – yes
Febrile diseases – yes
Hyperthermia – no

Menstruating women: a.m. temperature ↑ by

0.6°C with ovulation

Factors affecting body temperature;
age, pregnancy, endocrine alterations, exercise

Thermoregulation

Signals integrated by the thermoregulatory center
- peripheral receptors of warmth and cold
- temperature of blood bathing the region of

hypothalamus

Neutral environment
Metabolic rate of human body produces more

energy than is required to maintain the
temperature 37° C

Consequence : hypothalamus controls

temperature by mechanism of heat loss.

Body temperature

Heat generation - muscles , liver
Heat lost ; radiation 55%
evaporation 25% (airways 5%, skin 20%)
conduction 15%
convection 5%

Fever

Pyrogens – substances that induce fever

Exogenous – mostly products or toxins from microorganisms

, lipopolysaccharide (LPS) from gram-negative bacteria.

Endogenous – produced by host during systemic or local

inflammatory response, e.g by stimulated monocytes or
macrophages.

LPS itself induces fever but also stimulates macrophages to

release endogenous pyrogens !

exogenous

endogenous

Microorganisms and
their products ,toxins,
gram-negative, gram-

positive bacteria

Antigen-antibody
complexes with
complement

,

LPS –

lipopolysaccharide
1ng/kg

Complement cleavage

products

Peptidoglycans

Bile acids,

Lipoteichoic acid

Steroid hormone
metabolities
Some cytokines: Il-1α,
Il1β
TNFα, IFNα, Il-6

pyrogens

• IL-1α , Il-1β – most pyrogenic
• Intravenous administration (1 to 10 ng/kg)

causes chills, fever - 39°C within 1 hr

• Other pyrogenic cytokines act at many-times

higher doses

Fever

Infectious agents, endotoxins, inflammation
↓
Monocytes , macrophages, endothelial cells
↓
Pyrogenic cytokines
↓
Anterior hypothalamus
↓ ← antipyretics
Arachidonic acid conversion into PGE

2

↓
Elevated thermoregulation set point
↓
Elevated heat conservation and production
↓
fever

Fever

More PGE

2

in anterior hypothalamus

Rise in thermoregulatory set point
• - signals to efferent nerves
Sympathetic nerves – vasoconstriction of peripheral blood

vessels

• Signals to cortex
Initiation of behavioral changes – seeking a warm

environment, putting on more clothes, special posturing

Result – rise in body temperature by 2 to 3°C
If not enough ?
shivering

Antipyretics

Endogenous antipyretic substances:

Vasopressin, adrenocorticotropin, corticotropin releasing

hormone, α-melanocyte-stimulating hormone

(they alter ability of endogenous pyrogens to stimulate

prostaglandin production)

Il-1 receptor antagonist (Il-1 Ra)
Soluble TNFα receptor fragments
Il-4 , Il-10, TGFβ
Cyclooxygenase inhibitors (aspirin, ibuprofen)
Vasodilatation
Sweating
Behavioral changes

Accompaniments of fever

Back pain
Generalized myalgias
Arthralgias all can be reproduced by

infusions of

Anorexia puriefied cytokines
Somnolence

Chills – sensation of cold
Rigor – profound chill with piloerection (goose flesh) +

chattering of the teeth and severe shivering

Accompaniments of fever

Alterations of mental status
Convulsions
Sweats – caused by activation of heat-loss mechanisms

(treatment with antipyretics) or elimination of febrile
status

Patterns of fever

Widespread use of antipyretics, glucocorticoids

and antibiotics can alter the course of fever so
that „classic” fever patterns are not seen

Temperature-pulse dissociation
Is seen in typhoid fever

Why humans develop

fever ?

• Fever increases chances of survival during

bacterial infection

• Decreases growth and virulence of several

bacterial species

e.g in past induced-fever was used for

neurosyphilis treatment

Type III pneumococci may autolyze at 41°C
• Stimulates phagocytic and bactericidal activity

of neutrophils

• Stimulates cytotoxic activity of lymphocytes

Costs of fever

Discomfort
Decreased quality of life
Reduced mental acuity
Sometimes delirium or stupor induction
Increased O

2

consumption : 13% per 1°C

Increased caloric and fluid requirements
Acceleration of muscle catabolism (Il-1 , TNFα)
Loss of body weight
Negative nitrogen balance
Single episode of temperature > 37.8 °C in the

first trimester of pregnancy increases the risk
of some defects in fetus.

Causes of hyperthermia

• Heat stroke
Exertional – exercise in higher than normal heat

and/or humidity

Nonexertional : anticholinergics, diuretics

• Drug-induced : amphetamine, cocaine, LSD,

antidepressants

• Endocrinopathy : thyrotoxicosis,

pheochromocytoma

Hypothermia and endocrine system

Increased secretion of
ACTH
TSH
Increase in plasma levels of
Cortisol
Catecholamines
Slight increase in thyroid hormones

Hypothermia and nervous system

• Decline in neuronal metabolism
• Decrease in nerve conduction velocity
• Delayed reflexes
• Dysarthria, ataxia, amnesia, confusion
• „paradoxical undressing”
Coma with isoelectric EEG in the case of severe

hypothermia

This is not brain death, this is reversible !

Hyporthermia and respiratory system

Exposure to cold causes
• Bronchorrhea
• Bronchospasm
• Tachypnea
• Hypoventilation (in more severe

hypothermia

• Increase in hemoglobin affinity to O

2

-

impaired O

2

delivery to hypothermic tissues

Hypothermia risk factors

• Elderly
• Homelessness
• Ethanol use
• Malnutrition
• Poverty
• Mental illness
• Use of neuroleptic medication
• Hypothyroidism
• Adrenal insufficiency
• Hypoglycemia
• Spinal cord injury – T1 or above

Hypothermia

Acute exposure to cold
Activation of cutaneous cold receptors
Posterior hypothalamus
Activation of sympathetic nervous system
Increase in muscle tone , shivering and peripheral

vasoconstriction

• Shivering increases metabolic rae from 40-60 kcal/h to

300 kcal/h

• When temperature drops below 30°C metabolic

processes slow and shivering stops – further
acceleration of hypothermia development

Hypothermia and ethanol

Ethanol
• Inhibits shivering
• Impairs hepatic gluconeogenesis
• Causes peripheral vasodilatation –

increase in heat loss

Hypothermia and heart function

Acute exposure to cold:
• Tachycardia
• Increased cardiac output
• Peripheral vasoconstriction
• Increased peripheral vascular resistance
Temperature < 32° C
• Impairement of cardiac conduction
• Decrease in heart rate and cardiac output
• Atriall fibrillation
Temperature < 28° C
• Ventricular fibrillation