THERMOREGULATION

Ginus Partadiredja
The Department of Physiology
UGM, Yogyakarta

Normal Body Temperature

Skin temperature rise and falls surroundings
Core temperature constant (36C 37.5C)
Body Temperature = Heat Production >< Heat Loss

Heat Production
Metabolic rate of the body:
Basal rate of metabolism of cells
Muscle activity
Thyroxine
Epinephrine, norepinephrine, sympathetic stimulation
Chemical activity in cells
Extra metabolism for digestion, absorption, storage of
food

Heat Loss
Heat is mostly produced in the liver, brain, heart, exercised
skeletal muscle
The rate of heat lost:
Conduction from the body core to the skin
The degree of vasoconstriction (sympathetic nerves)
Transfer from the skin to the surroundings
Insulator system (skin, subcutaneous tissue, fat)
Fat transfer 1/3 heat
Women = better insulation
Clothing; wet clothing

Heat Loss
Radiation infrared heat rays (60% total heat loss)
Conduction to solid objects (3%)
to air (15%) to water 30x of air
Convection conduction to the air first convection (air
currents) heat loss wind speed
heat conductivity in water >> than in air
Evaporation insensible evaporation (lungs + skin) = 600
700 ml/ day cannot be controlled
sweating evaporation can be controlled
the only means to get rid of heat in high
temperature environment

 Respiration evaporation (water droplets evaporated)

contribute to hypothermia in cool, windy, and dry
environments

Sweating

Stimulation of the anterior hypothalamus-preoptic area

sympathetic nerves cholinergic sweat glands

 Sweat secretion
coiled/ glandular portion primary secretion plasma
(except protein); Na = 142 mEq/L, Cl = 104 mEq/L
duct portion
slight stimulation low level salt
strong stimulation high level salt (50 60 mEq/L)
Aldosterone 15 30 g/day salt excreted (unacclimatized)
3 5 g/day salt

Role of the Hypothalamus

Anterior hypothalamic-preoptic area heat-sensitive
neurons & 1/3 cold-sensitive neurons (temperature
sensors)
Skin receptors: 10x cold receptors > warmth receptors
preventing hypothermia
Chilled body causes:
1. shivering
2. sweating inhibition
3. skin vasoconstriction
Deep tissue receptors (spinal cord, abdominal viscera,
great veins around upper abdomen & thorax)
Posterior hypothalamus combine & integrate
temperature sensory signals

Temperature Decreasing Mechanisms:

1. Vasodilation of skin blood vessels
Inhibition of the sympathetic center (posterior
hypothalamus)
2. Sweating
3. Decrease in heat production

Temperature Increasing Mechanisms:

1. Skin vasoconstriction
Stimulation of sympathetic centers (posterior
hypothalamus)
2. Piloerection
Entrapping insulator air
3. Increase in thermogenesis
Shivering
Sympathetic excitation
Thyroxine

Shivering
Heat center (anterior hypothalamic-preoptic area)
inhibition
Primary motor center for shivering (dorsomedial portion of
posterior hypothalamus)
stimulation
Cold signals (skin & spinal cord)
brain stem
facilitating the activity of anterior motor neuron
increasing tone

Sympathetic excitation of heat production

Sympathetic stimulation the rate of cellular metabolism
increase (chemical thermogenesis; excess foodstuff
oxidized)
Brown fat (animals, not adult humans) large number of
special mitochondria
Infants brown fat in interscapular space the rate of
heat production increase 100%

Thyroxine
Cooling anterior hypothalamic-preoptic area
Thyrotropin-releasing hormone (hypothalamus)
Thyroid stimulating hormone (anterior pituitary)
Thyroxine
Increase the rate of cellular metabolism (several weeks)

Behavioral Control of Body Temperature

Feeling hot or cold due to the changes of internal body
temperature moving into heated room or wearing wellinsulated clothing
Local Skin Temperature Reflexes
Local vasodilatation or sweating

Set Point for Temperature Control

37.1C set point of the temperature control mechanism
The set point the degree of activity of the heat
temperature receptors in the anterior hypothalamic-preoptic
area
Skin & deep body tissues (spinal cord & abdominal viscera)
also affect body temperature regulation change of
hypothalamic set point
Set point increase as skin temperature decrease (sweating
at high skin temperature & low hypothalamic temperature)

Abnormalities of Body Temperature Regulation

Fever
Abnormalities in the brain (brain tumor) increase
body temperature
Toxic substances on temperature-regulating centers
(pyrogens) rising the set-point
Pyrogens: proteins, breakdown products of proteins,
lipopolysaccharide toxins of bacteria or degenerating body
tissues
The increase of set-point heat conservation & heat
production increase

 Bacterial pyrogens (endotoxins of gram-negative bacteria)

several hours
Bacteria
Leukocytes, macrophages, large granular killer lymphocytes
Interleukin 1 (leukocyte pyrogen/ endogenous pyrogen)
E.g. Arachidonic acid Prostaglandins (E2) hypothalamus
Aspirin

Characteristics of Febrile Conditions

The set-point increase & blood temperature < set-point
Chills & cold feeling
cold skin (vasoconstriction),
shivering, piloerection, epinephrine secretion
Body temperature reaches the high temperature
hypothalamic set-point
Neither feel cold or hot

The factor (e.g. pyrogens) removed

The set-point reduced to a lower value
Hypothalamus attempt to reduce body temperature
Intense sweating, hot skin (vasodilatation) = flush/crisis

Hyperthermia
Hyperthermia:
-Thermoregulatory failure (excessive heat production,
excessive environmental heat, impaired heat dissipation)
-Hypothalamic set-point is normal
-Peripheral mechanisms unable to match the set point
Fever:
- Intact homeostasis responses
- Hypothalamic set-point increases due to pyrogenic cytokines
- Peripheral mechanisms are competent conserve heat

Causes of Hyperthermia
Excessive heat production:

Diminished heat dissipation:

Exertional hyperthermia

Heat stroke (classic)*

Heat stroke (exertional)*

Extensive use of occlusive

dressings

Malignant hyperthermia of
anesthesia

Dehydration

Neuroleptic malignant
syndrome*

Autonomic dysfunction

Lethal catatonia

Anticholinergic agents

Thyrotoxicosis

Neuroleptic malignant
syndrome*

Pheochromocytoma

Disorders of hypothalamic
function:

Salicylate intoxication

Neuroleptic malignant
syndrome*

Drug abuse (cocaine,

amphetamine)
* Mixed pathogenesis

Cerebrovascular accidents

Exertional Hyperthermia
Acclimatized athletes 2 L sweat/ hour evaporation of
900 kcal/ hour
Heat dissipation skin vasodilatation & sweating limited
by volume depletion, ambient temperature & humidity
Intense, prolonged exercise in humid weather
hyperthermia
Exertional hyperthermia usually self-limited & asymptomatic
Adverse effects: muscle cramps, heat exhaustion,
heatstroke
Prevention: Acclimatization (athlete), light clothing, avoid
direct sunlight, hydration
Treatment: Rest, oral rehydration, IV fluids, evacuation to
cool environment

Heatstroke
One can withstand several hours 130F in dry air (convection)
One can only tolerate up to 94F in 100% humidified air
Heatstroke if body temperature > 105F - 108F

Heatstroke
Heatstroke: - Exertional heat stroke (athletes & military)
- Classic heat stroke (sedentary, elderly)
Exertional heat stroke: Lack of acclimatization, lack of
cardiovascular conditioning, dehydration, heavy clothing,
excessive exertion
Classic heat stroke: Impaired heat dissipation (anhidrosis),
cardiovascular diseases, neurologic disorders, impaired
consciousness, obesity, anticholinergic or diuretic agents,
dehydration, very old/ young
Prevention: Hydration, minimizing anticholinergic or diuretic
agents, cool environments

 Symptoms & signs: Dizziness, abdominal distress,

vomiting, delirium/ stupor/ coma, hypotension, tachycardia,
hyperventilation, hemorrhages, degeneration, in brain, liver,
kidneys
Laboratory findings: Hemoconcentration, proteinuria,
microscopic hematuria, abnormal liver function, elevated
muscle enzymes levels, rhabdomyolysis (exertional),
disseminated intravascular coagulation (exertional),
hypoglycemia (exertional), electrolyte & acid-base
disturbance; respiratory alkalosis & hypokalemia (early
phase) lactic acidosis & hyperkalemia (later phase)

 Mortality: shock, arrhythmias, myocardial ischemia, renal

failure, neurologic dysfunction
Treatment:
- Removal of clothing
- Sponge/ spray cooling/ cold water bath/ ice body surface
- Oral hydration
- Intravenous hydration with room temperature fluids
- Correction of electrolyte/ acid-base disturbance
- Cardiovascular monitoring & support

Malignant Hyperthermia of Anesthesia

Excessive release of calcium from the sarcoplasmic reticulum
(in response to anesthetic drugs) severe muscle
hypermetabolism
Hereditary, autosomal dominant
Most anesthetic drugs, especially halogenated inhalation &
depolarizing muscle relaxants
Symptoms & signs: > 41C, severe muscle rigidity,
hypotension, hyperpnea, tachycardia, arrhythmias, hypoxia,
hypercapnia, lactic acidosis, hyperkalemia, rhabdomyolysis,
disseminated intravascular coagulation
Treatment: Dantrolene sodium IV (inhibit the release of
calcium), interruption of anesthesia, correction of hypoxia &
metabolic disturbance, cardiovascular support, physical cooling

Neuroleptic Malignant Syndrome

Neuroleptic agents: phenotiazines, butyrophenones,
thioxanthenes, haloperidol (most often)
Blockade of dopaminergic receptors in the corpus striatum
Symptoms & signs: > 41C, skeletal muscle rigidity
excessive heat impairs hypothalamic thermoregulation,
extrapyramidal abnormalities, altered consciousness,
autonomic dysfunction (labile blood pressure,
tachyarrhythmias, incontinence) impairs heat dissipation
Laboratory findings: Hemoconcentration, leukocytosis,
hypernatremia, acidosis, electrolyte disturbances,
rhabdomyolysis, abnormal renal & hepatic functions
Treatment: Neuroleptic withdrawal, metabolic &
cardiovascular support, dantrolene sodium, bromocriptine
mesylate (dopamine agonist)

Hormonal Hyperthermia
Thyrotoxicosis (most common)
Pheochromocytoma crisis: High level of norepinephrine
skin vasoconstriction & hypermetabolism
Adrenal insufficiency
Hypoglycemia
Hyperparathyroidism

Miscellaneous Causes of Hyperthermia

Simple dehydration volume depletion vasoconstrition
& decreased sweating impair heat dissipation
Extensive occlusive dressings
Infections
Anticholinergic drugs
Cocaine
Amphetamine
Alcohol abuse & withdrawal
Salicylate intoxication
Therapeutic Hyperthermia
Nasal hyperthermia for viral nasopharyngitis
Adjunctive therapy for cancers

The Consequences of Hyperthermia

Extreme hyperthermia: Confusion, delirium, stupor, coma
Metabolic abnormalities: Hypoxia, respiratory alkalosis,
metabolic acidosis, hypokalemia, hyperkalemia,
hypernatremia, hypophosphatemia, hypomagnesemia,
hypoglycemia
Hematologic abnormalities: Hemoconcentration,
leukocytosis, thrombocytosis, disseminated intravascular
coagulation
Azotemia, elevated serum levels of liver and muscle
enzymes

Management of Hyperthermia
1. Diagnose & treat underlying disoder
2. Cardiovascular & metabolic support
3. Antipyretic therapy (39C, young, elderly, underlying
diseases) mandatory in heat stroke, malignant
hyperthermia; indicated in neuroleptic malignat syndrome,
thyrotoxic crisis
4. Pharmacologic agents to lower hypothalamic set-point (in
fever) acetaminophen, aspirin
5. Physical cooling (in hyperthermia) removing
bedclothes, bedside fans, sponging with tepid water/
alcohol, hypothermic mattresses, ice packs, ice water
immersion (most effective)
6. IP cool fluid, gastric lavage or ice water enema,
extracorporeal circulation

Exposure of the Body to Extreme Cold

Frostbite

Temperature regulation greatly impaired < 94F; lost < 85F

due to the depression of the rate of chemical heat production,
sleepiness (depresses the activity of CNS)
Exposure to ice water 20 death caused by heart
standstill/ fibrillation

Hypothermia Common causes of hypothermia:

Dermal diseases:

Metabolic:

- Burns

- Hypoadrenalism

- Exfoliative dermatitis

- Hyperadrenalism

- Severe psoriasis

- Hypothyroidism

Drug induced:

Neurologic:

- Ethanol

- Acute spinal cord transection

- Phenothiazines

- Head trauma

- Sedative-hypnotics

- Stroke

Environmental:

- Tumor

Immersion

- Wernickes disease

Nonimmersion

Neuromuscular inefficiency:

Iatrogenic:

- Age extreme

- Aggressive fluid resuscitation

- Impaired shivering

- Heat stroke treatment

- Lack of acclimatization
Sepsis

Stages of Hypothermia and Clinical Features: Mild

Hypothermi Body
a Zone
Temperatur
e

Clinical Features

Mild

Initial excitation phase to combat

cold:

32.2C 35C

Hypertension
Shivering
Tachycardia
Tachypnea
Vasoconstriction
With time and onset of fatigue:
Apathy
Ataxia
Cold diuresis kidneys lose
concentrating ability
Hypovolemia

Stages of Hypothermia and Clinical Features:

Moderate
Hypothermi Body
Clinical Features
a Zone
Temperature
Moderate

28C
32.2C

Atrial dysrhythmias
Decreased heart rate
Decreased level of consciousness
Decreased respiratory rate
Dilated pupils
Diminished gag reflex
Extinction on shivering
Hyporeflexia
Hypotension
J wave (electrocardiogram)

Stages of Hypothermia and Clinical Features: Severe

Hypothermi Body
a Zone
Temperatur
e

Clinical Features

Severe

Apnea

< 28C

Coma
Decreased or no activity on
electroencephalography
Nonreactive pupils
Oliguria
Pulmonary edema
Ventricular dysrhythmias/ asystole

Laboratory Findings in Hypothermia

1. Renal failure (secondary to rhabdomyolysis/ acute tubular
necrosis
2. Rapid changes of electrolyte levels (potassium, due to
rewarming)
3. Coagulopathies self limited
4. Inaccurate leukocytes count antibiotics in neonates,
elderly, immunocompromised patients

Management of Hypothermia
1. Glucose (most patients depleted glycogen stores)
2. Thiamine (a possibility of alcohol abuse)
3. Remove wet clothing, replaced with blankets
4. Avoid excessive movement and nasogastric tube
5. Aggressive resuscitation with warm fluid
6. Restricted steroids for adrenal insufficiency & failure of
temperature normalization
7. Defibrillation for ventricular fibrillation (many
electrocardiographic changes: tachycardia, bradycardia,
atrial fibrillation, ventricular fibrillation, asystole,
prolongation of PR, QRS, and QT intervals, J waves)

Rewarming
1. Mild hypothermia, intact thermoregulatory mechanisms,
normal endocrine function, adequate energy stores
passive rewarming (insulation, moving patient to warm, dry
environment)
2. Intact circulation active external rewarming (hot water
bottles, heating pads, forced-air warming system,
immersion of hands or feet in 45C water, negative
pressure to forearm inserted in device containing heated
air in a vacuum of -40 mmHg)
Complications: core temperature afterdrop, rewarming
acidosis (lactic acid from the periphery central
circulation, rewarming shock (peripheral vasodilatation)

3. Active core rewarming moderate & severe hypothermia:

a. Airway rewarming with humidified oxygen at 40C
(increases core temperature by 1C- 2.5C/ hour)
b. Intravenous fluids (5% dextrose and normal saline) heated
to 40C - 45C
c. Extracorporeal blood rewarming most effective
(cardiopulmonary bypass, arteriovenous rewarming,
venovenous rewarming, hemodialysis) increases core
temperature by 1C - 2C/ 3-5 minutes
d. Warm lavage (gastric, colonic, bladder lavage, peritoneal
dialysis). Peritoneal dialysis normal saline, lactated
ringers, dialysate solution heated 40C - 45C, 6 10 L/
hour combined with O2 increases body temperature 1C
- 3C/ hour

Active core rewarming:

Closed thoracic lavage: thoracostomy tube mediastinal
irrigation increases core body temperature by 8C/ hour
Disposition:
Lowest temperature survived: 14.2C (child) & 13.7C (adult)
Resuscitation SHOULD NOT BE DISCONTINUED (even if
appears to be dead) until the core temperature > 30C-32C
and no signs of life

Summary of Management of Hypothermia

1. Passive external warming (removal of cold, wet clothing;
movement to a warm environment)
2. Active external rewarming (insulation with warm blankets)
3. Active core rewarming (warmed intravenous fluid infusions,
heated humidified oxygen, body cavity lavage,
extracorporeal blood warming)

Hypothermia

Cardiopulmonary arrest?
Yes

No

Secure airway
Core body temperature > 32C?
Defibrillate ventricular fibrillation
Intact energy stores?
Intact thermoregulatory mechanisms? only
Initiate CPR
Bedside glucose, thiamine
No
Yes
Warmed IV fluids
Heated humidified O2
Treat underlying etiology
Antibiotics and/or steroids as
Passive
appropriate
external
Is extracorporeal rewarming
rewarming
available?
Unsuccessful?
Minimally invasive core
rewarming
(e.g. warmed IV fluids)
truncal active external
rewarming

N
o

Yes

Active core
rewarming
Rewarm to > 30C - 32C

Antidysrythmics and/or defibrillation as appropr

References
1. Guyton AC & Hall JE (2006). Textbook of Medical
Physiology, 11th ed. Chapter 73, Pages: 889 901
2. McCullough L & Arora S (2004). Diagnosis and
Treatment of Hypothermia. American Family Physician
70(12): 2325 2332
3. Simon HB (1993). Hyperthermia. The New England
Journal of Medicine 329: 483 - 487