How does the body maintain a constant internal temperature

The thermoregulatory system uses both feedback and feedforward controls to

maintain a constant body core temperature of 37oC by matching body heat loss and heat
production. However, there are slight changes in body core temperature depending on
time of day and the stage of menstrual cycle in women. Circadian body temperature
rhythm of the autonomous nervous system means that body core temperature is lowest
between 3-6 am and highest between 3-6 pm. In women, the body core temperature
increases about 0.5 oC during the post-ovulatory phase. Ambient temperature changes are
sensed by cutaneous thermoreceptors which control the feedforward control mechanism
of the thermoregulatory system. When the body core temperature does change, this is
sensed by thermoreceptors in the preoptic anterior hypothalamus which act as sensors in
the negative feedback control. Heat can be lost by radiation, conduction, convection and
evaporation. Heat loss by evaporation occurs on the surface of skin and respiratory tract,
and the evaporative rate is dependent on the water vapour pressure gradient. Cutaneous
vasodilation and sweating increase heat dissipation by convection and evaporation so the
physiological control of cutaneous blood flow and eccrine sweat glands are important
effectors of the thermoregulatory system. The importance of body core temperature
homeostasis is illustrated by failures in the thermoregulatory system causing hypo- and
hyperthermia (body core temperature below or above the thermoregulatory set-point)
leading to severe clinical consequences such as heat stroke and death if untreated. Fever
differs from hyperthermia because the rise in body core temperature is due to an increase
in the hypothalamic body core temperature set-point caused by pyrogens. Malignant
hyperthermia can be induced in genetically susceptible individuals with mutations in the
RYR gene by depolarising muscle blockers such as suxamethonium and halogenated
volatile anaesthetics and require dantrolene treatment.

Fig 58-4 p.1237 from Boron

Thermoreceptors are free nerve endings and can be either warmth or cold
receptors. Warmth receptors firing rate increases between 30oC and 45oC, and cold
receptors discharge rate increases between 40oC and 25oC but temperature below 25oC
decreases firing of cold receptors. Cutaneous thermoreceptors detect ambient
temperature and thermoreceptors in the preoptic anterior hypothalamus detect body core
temperature. The hypothalamic thermoregulatory centre integrates information about
body core temperature and ambient temperature and directs appropriate changes in
cutaneous blood flow, sweat glands and skeletal muscle shivering to keep a constant
internal temperature. When body core temperature rises above 37oC, this is detected by
thermoreceptors in the preoptic anterior hypothalamus which leads to an increase in heat
loss by inducing cutaneous vasodilation and increasing sweating by eccrine sweat glands.
Conversely, a drop in body core temperature below 37oC causes shivering of skeletal
muscles which increases heat production, and a reduction in heat loss by inducing
cutaneous vasoconstriction and inhibition of sweating by eccrine sweat glands.
 When the thermoregulatory system is overwhelmed by excessive metabolic
production of heat, excessive environmental heat or impaired heat dissipation, rate of heat
production surpass rate of heat dissipation resulting in hyperthermia. During prolonged
heavy exercise, heat loss mechanisms are activated and heat dissipation slowly increases
which eventually matches heat production. However, exertional hyperthermia persists
during exercise because a rising body core temperature is needed to provide the error
signal to the hypothalamic thermoregulatory centre to activate heat loss mechanisms.
Moreover, dehydration during prolonged exercise reduces heat loss by evaporation as
sweating becomes limited. The risk of hyperthermia is increased by warm weather and
high ambient humidity as heat loss by radiation, convection and evaporation falls.
Excessive hyperthermia (>41oC) cause heat stroke which is characterized by delirium,
stupor, hypotension, tachycardia and hyperventilation. Altered sensorium occurs because
cutaneous vasodilation in response to a raised body core temperature reduces arterial
pressure which decreases brain perfusion. The high body core temperature causes
fibrinolysis and activation of clotting factors leading to disseminated intravascular
coagulation (DIC) which result in systemic vascular thrombosis and haemorrhage.
Furthermore, excessively high temperature damages cell membranes of skeletal and
myocardial muscles causing rhabdomyolysis (release of intracellular contents including
myoglobin from damaged muscle cells) and myocardial necrosis. Treatments for heat
stroke include removal of clothing, physical cooling by immersion in ice water and oral
hydration.

The most common cause of hypothermia is prolonged immersion in cold water

because the convective heat-transfer coefficient of water is approximately 100-fold
greater than air. The drop in body core temperature is detected by hypothalamic
thermoreceptors and leads to cutaneous vasoconstriction and shivering but heat loss
continues resulting in progressive hypothermia. Treatments for hypothermia include
warming with blankets and injection of warm intravenous fluid to restore normal body
core temperature.

Excessively high body core temperature can also occur when the
thermoregulatory system is intact such as during fever where pyrogens raise the
hypothalamic set point for body core temperature. Infection by Gram-negative bacteria
stimulates macrophages to release cytokines including pyrogens such as IL-1 and TNF-α.
These pyrogens stimulate release of PGE2 by endothelial cells in the organum
vasculosum laminae terminalis (OVLT) which lies in the wall of the third ventricle. PGE2
elevates the body core temperature set point in the hypothalamus and thermoregulatory
system respond by increasing shivering, inducing cutaneous vasoconstriction and
reducing sweating to increase body core temperature to the new set-point. It is believed
that hyperthermia during fever increases immune response against infection.

An interesting type of hyperthermia is a rare autosomal dominant disorder called

malignant hyperthermia (MH) which is induced by depolarising muscle blocking agents
such as suxamethonium in genetically susceptible individuals. Susceptibility to MH can
be screened for using the “caffeine-halothane contracture test”. MH is associated with
mutations in the RYR gene (human chromosome 19q13.1) encoding ryanodine channels,
such as a Val-2168-Met mutation, causing sustained Ca2+ release from the SR when
suxamethonium is administered resulting in severe muscle hypermetabolism,
hyperthermia and muscle rigidity. MH is treated by intravenous administration of
dantrolene, a ryanodine receptor blocker.

In conclusion, body core temperature homeostasis is important to prevent

disruption of physiological processes as the structure of proteins such as enzymes are
altered by temperature changes which leads to impaired function. Changes in the ambient
temperature and body core temperature are detected by thermoreceptors and information
about temperature is integrated in the hypothalamic thermoregulatory center which
compares body core temperature with the thermoregulatory set point. Deviations from the
set value leads to appropriate changes in cutaneous vasomotor tone, sweat gland secretion
and levels of shivering which restore normal body core temperature.
 How does the body maintain a constant internal temperature

SYLLABUS
Body temperature regulation
Normal body temperature and its circadian and menstrual rhythms
Concept of ‘core temperature’ and the importance of its maintenance
Definition of hyperthermia and hypothermia
Contributions of convection, evaporation, conduction and radiation to heat loss
Thermoneutral zone and its relation to clothing
Temperature control in the thermoneutral zone of core temperatures by skin bloow flow
and piloerection; outside this zone, shivering as an anti-drop response, sweating as an
anti-rise response
Cutaneous blood supply in apical and non-apical areas
Innervation of sweat glands
Peripheral temperature receptors
Temperature pathways in the spinothalamic tract. Responses to low and high ambient
temperature
Central core temperature / pyrogen receptors in anterior hypothalamus

EXTENSION
Relation between metabolic rate and body mass in mammals
Brown fat as a thermogenic organ in babies
Heat acclimatization of sweating
Peripheral cold injuries
Peripheral heat injury
Fast and slow temperature fibres
Torpor and hibernation
Causes and features of hypothermia, including therapeutic uses.
Pyrexia. Causes and features of hyperthermia, including heat stroke.
Malignant hyperthermia.

http://content.nejm.org/cgi/content/full/329/7/483

June 2003: What physiological mechanisms are involved in the detection and regulation
of the body core temperature?

March 2005: Describe the control systems that tend to hold human core temperature
constant when ambient temperature changes.
September 2005: How is body temperature held relatively constant in the face of abrupt
changes of environmental temperature? How do cutaneous and core mechanisms
contribute to this relative constancy?

March 2006: Describe the short and long term changes that occur in the body when
ambient temperature rises.

9. Describe the control systems that tend to hold human core temperature constant
when ambient temperature changes.
65 answers, average 4.8. The examiners were disappointed that a question that
specifically asked the candidates to describe a control system should produce few
essays that so much as mentioned the words feedback, feedforward, setpoint or
gain. The few who did were appropriately rewarded. The most common error
was to have arteriovenous anastomoses opening up in the cold (to shunt blood
flow away from the more superficial capillaries) and the most common omission
was to ignore the direct, local effects of temperature on cutaneous blood vessels.
One candidate reduced his basal metabolic rate by keeping still. A few candidates
though sweat is hypertonic or isotonic to plasma and one, having stated this, said
that raised ADH secretion occurs to counter it. Another drew our attention to
his/her shortcomings by apologising profusely for them.