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:
Exertional hyperthermia Heat stroke (exertional)* Malignant hyperthermia of anesthesia Neuroleptic malignant syndrome* Lethal catatonia Thyrotoxicosis Pheochromocytoma Salicylate intoxication Drug abuse (cocaine, amphetamine)

Diminished heat dissipation:

Heat stroke (classic)* Extensive use of occlusive dressings Dehydration Autonomic dysfunction Anticholinergic agents Neuroleptic malignant syndrome* Disorders of hypothalamic function: Neuroleptic malignant syndrome* Cerebrovascular accidents

Delirium tremens
Status epilepticus Generalized tetanus

Encephalitis
Sarcoidosis & granulomatous infections Trauma

* 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: > 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: - Burns - Exfoliative dermatitis - Severe psoriasis Drug induced: - Ethanol - Phenothiazines Metabolic: - Hypoadrenalism - Hyperadrenalism - Hypothyroidism Neurologic: - Acute spinal cord transection - Head trauma

- Sedative-hypnotics
Environmental:
-

- Stroke
- Tumor - Wernickes disease Neuromuscular inefficiency: - Age extreme - Impaired shivering - Lack of acclimatization Sepsis

Immersion Nonimmersion

Iatrogenic: - Aggressive fluid resuscitation - Heat stroke treatment

Stages of Hypothermia and Clinical Features: Mild

Hypothermia Body Zone Temperature Mild Clinical Features

32.2C - 35C Initial excitation phase to combat cold: Hypertension Shivering Tachycardia Tachypnea

Vasoconstriction
With time and onset of fatigue: Apathy Ataxia Cold diuresis kidneys lose concentrating ability Hypovolemia Impaired judgment

Stages of Hypothermia and Clinical Features: Moderate

Hypothermia Body Zone Temperature Clinical Features

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

Hypothermia Body Zone Temperature Severe < 28C Clinical Features Apnea 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?

No
Core body temperature > 32C? Intact energy stores? Intact thermoregulatory mechanisms? No Yes

Yes
Secure airway Defibrillate ventricular fibrillation only Initiate CPR Bedside glucose, thiamine Warmed IV fluids Heated humidified O2 Treat underlying etiology Antibiotics and/or steroids as appropriate Is extracorporeal rewarming available? No Active core rewarming Rewarm to > 30C - 32C Yes

Passive external rewarming

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

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