THERMOREGULATIONTHERMOREGULATIONGinus PartadiredjaGinus Partadiredja

The Department of PhysiologyThe Department of Physiology

UGM, YogyakartaUGM, 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 well-

insulated clothing

Local Skin Temperature Reflexes

• Local vasodilatation or sweating

Set Point for Temperature Control

• 37.1°C 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

Excessive heat production:Excessive heat production: Diminished heat dissipation:Diminished heat dissipation:

Exertional hyperthermiaExertional hyperthermia Heat stroke (classic)*Heat stroke (classic)*

Heat stroke (exertional)*Heat stroke (exertional)* Extensive use of occlusive Extensive use of occlusive dressingsdressings

Malignant hyperthermia of Malignant hyperthermia of anesthesiaanesthesia

DehydrationDehydration

Neuroleptic malignant Neuroleptic malignant syndrome*syndrome*

Autonomic dysfunctionAutonomic dysfunction

Lethal catatoniaLethal catatonia Anticholinergic agentsAnticholinergic agents

ThyrotoxicosisThyrotoxicosis Neuroleptic malignant Neuroleptic malignant syndrome*syndrome*

PheochromocytomaPheochromocytoma Disorders of hypothalamic Disorders of hypothalamic function:function:

Salicylate intoxicationSalicylate intoxication Neuroleptic malignant Neuroleptic malignant syndrome*syndrome*

Drug abuse (cocaine, Drug abuse (cocaine, amphetamine)amphetamine)

Cerebrovascular accidentsCerebrovascular accidents

Delirium tremensDelirium tremens EncephalitisEncephalitis

Status epilepticusStatus epilepticus Sarcoidosis & granulomatous Sarcoidosis & granulomatous infectionsinfections

Generalized tetanusGeneralized tetanus TraumaTrauma

Causes of Hyperthermia

* Mixed pathogenesis

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: > 41°C, 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: > 41°C, 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

• 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

Frostbite

Hypothermia Common causes of hypothermia:

Dermal diseases:Dermal diseases: Metabolic:Metabolic:

- Burns- Burns - Hypoadrenalism- Hypoadrenalism

- Exfoliative dermatitis- Exfoliative dermatitis - Hyperadrenalism- Hyperadrenalism

- Severe psoriasis- Severe psoriasis - Hypothyroidism- Hypothyroidism

Drug induced:Drug induced: Neurologic:Neurologic:

- Ethanol- Ethanol - Acute spinal cord transection- Acute spinal cord transection

- Phenothiazines- Phenothiazines - Head trauma- Head trauma

- Sedative-hypnotics- Sedative-hypnotics - Stroke- Stroke

Environmental:Environmental: - Tumor- Tumor- ImmersionImmersion - Wernicke’s disease- Wernicke’s disease- NonimmersionNonimmersion Neuromuscular inefficiency:Neuromuscular inefficiency:

Iatrogenic:Iatrogenic: - Age extreme- Age extreme

- Aggressive fluid resuscitation- Aggressive fluid resuscitation - Impaired shivering- Impaired shivering

- Heat stroke treatment- Heat stroke treatment - Lack of acclimatization- Lack of acclimatization

SepsisSepsis

Stages of Hypothermia and Clinical Features: Mild

HypothermHypothermia Zoneia Zone

Body Body TemperaturTemperaturee

Clinical FeaturesClinical Features

MildMild 32.2°C - 32.2°C - 35°C35°C

Initial excitation phase to combat Initial excitation phase to combat cold:cold:

HypertensionHypertension

ShiveringShivering

TachycardiaTachycardia

TachypneaTachypnea

VasoconstrictionVasoconstriction

With time and onset of fatigue:With time and onset of fatigue:

ApathyApathy

AtaxiaAtaxia

Cold diuresis – kidneys lose Cold diuresis – kidneys lose concentrating abilityconcentrating ability

HypovolemiaHypovolemia

Impaired judgmentImpaired judgment

Stages of Hypothermia and Clinical Features: Moderate

HypothermHypothermia Zoneia Zone

Body Body TemperaturTemperaturee

Clinical FeaturesClinical Features

ModerateModerate 28°C – 28°C – 32.2°C32.2°C

Atrial dysrhythmiasAtrial dysrhythmias

Decreased heart rateDecreased heart rate

Decreased level of consciousnessDecreased level of consciousness

Decreased respiratory rateDecreased respiratory rate

Dilated pupilsDilated pupils

Diminished gag reflexDiminished gag reflex

Extinction on shiveringExtinction on shivering

HyporeflexiaHyporeflexia

HypotensionHypotension

J wave (electrocardiogram)J wave (electrocardiogram)

Stages of Hypothermia and Clinical Features: Severe

HypothermHypothermia Zoneia Zone

Body Body TemperaturTemperaturee

Clinical FeaturesClinical Features

SevereSevere < 28°C< 28°C ApneaApnea

ComaComa

Decreased or no activity on Decreased or no activity on electroencephalographyelectroencephalography

Nonreactive pupilsNonreactive pupils

OliguriaOliguria

Pulmonary edemaPulmonary edema

Ventricular dysrhythmias/ asystoleVentricular 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 45°C 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 40°C

(increases core temperature by 1°C- 2.5°C/ hour)

b. Intravenous fluids (5% dextrose and normal saline) heated

to 40°C - 45°C

c. Extracorporeal blood rewarming most effective

(cardiopulmonary bypass, arteriovenous rewarming,

venovenous rewarming, hemodialysis) increases core

temperature by 1°C - 2°C/ 3-5 minutes

d. Warm lavage (gastric, colonic, bladder lavage, peritoneal

dialysis). Peritoneal dialysis normal saline, lactated

ringers, dialysate solution heated 40°C - 45°C, 6 – 10 L/

hour combined with O2 increases body temperature 1°C

- 3°C/ hour

Active core rewarming:

• Closed thoracic lavage: thoracostomy tube mediastinal

irrigation increases core body temperature by 8°C/ hour

Disposition:

• Lowest temperature survived: 14.2°C (child) & 13.7°C (adult)

• Resuscitation SHOULD NOT BE DISCONTINUED (even if

appears to be dead) until the core temperature > 30°C-32°C

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)

Cardiopulmonary arrest?

NoYes

Core body temperature > 32°C?Intact energy stores?Intact thermoregulatory mechanisms?

No

No

Yes

Yes

Passive external rewarming

Unsuccessful?

Minimally invasive core rewarming(e.g. warmed IV fluids) truncal active external rewarming

Secure airwayDefibrillate ventricular fibrillation onlyInitiate CPRBedside glucose, thiamineWarmed IV fluidsHeated humidified O2

Treat underlying etiologyAntibiotics and/or steroids as appropriate

Hypothermia

Is extracorporeal rewarming available?

Active core rewarming

Rewarm to > 30°C - 32°C

Antidysrythmics and/or defibrillation as appropriate

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