Thermoregulation and Pathogenesis of Fever

Heat production

BMR from vital organs (liver, brain, heart, kidneys, skeletal muscle)

Heat production voluntary

exercise increases metabolic activity

Heat production involuntary

shivering increases muscle metabolism

Heat production hormones

catecholamines and thyroxin stimulate metabolism

Heat loss radiation

~60% of heat loss at rest in neutral environment

Heat loss conduction

heat transfer by direct contact with cooler surfaces

Heat loss convection

heat transfer enhanced by wind or water movement across skin

Heat loss evaporation

sweating via eccrine glands provides vaporative cooling

Skin vasodilation

increases cutaneous blood flow enhancing heat loss

Skin vasoconstriction

reduces cutaneous blood flow conserving heat

Sympathetic adrenergic control

regulates vasodilation and vasoconstriction

Thermoregulation definition

body’s ability to maintain core temperature despite environment

Normal core temperature

36.5–37.5°C

Thermoregulatory control centre

hypothalamus maintains set point ~37°C

Anterior hypothalamus

mediates heat loss responses

Posterior hypothalamus

mediates heat gain responses

Central thermoreceptors

located in hypothalamus monitoring blood temperature

Peripheral thermoreceptors

located in skin detecting environmental changes

Negative feedback loop stimulus

thermal change activates receptors

Negative feedback loop integration

hypothalamus processes afferent signals

Negative feedback loop efferent

sweating and vasodilation initiated

Negative feedback loop outcome

return to set point temperature

Sweat gland types

eccrine for thermoregulation, apocrine for scent

Sweating neural control

cholinergic sympathetic pathways stimulate eccrine glands

Autonomic nervous system role

sympathetic efferents regulate vessels and sweat glands

Parasympathetic role

minimal in thermoregulation

Desert environment challenge

extreme heat and dehydration risk

Desert response

increased sweating, vasodilation, behavioral shade seeking

Desert risk

heat stroke due to impaired cooling

Snow skiing challenge

cold exposure risk of hypothermia and frostbite

Snow skiing response

vasoconstriction, shivering, layered clothing insulation

Snow skiing risk

hypothermia and frostbite injury

Immersion in ice water challenge

cold shock response with rapid conduction heat loss

Immersion in ice water response

vasoconstriction, cardiovascular strain

Immersion in ice water risk

rapid hypothermia and arrhythmias

Snorkeling in warm water challenge

neutral environment but prolonged immersion stress

Snorkeling in warm water response

mild heat loss, dehydration risk

Snorkeling in warm water risk

overheating with activity and muscle fatigue

Fever definition

regulated increase in body temperature due to raised hypothalamic set point

Hyperthermia definition

unregulated rise due to failure of heat loss mechanisms without set point change

Exogenous pyrogens

bacterial toxins stimulate leukocytes

Cytokines in fever

IL-1 and TNF-α released by leukocytes

Cytokines action

stimulate hypothalamus to increase PGE2

PGE2 role

raises hypothalamic set point temperature

Chill phase of fever

vasoconstriction and shivering raise body temperature

Plateau phase of fever

temperature stabilizes at new set point

Defervescence phase of fever

vasodilation and sweating reduce temperature when set point normalizes

Antipyretics mechanism

NSAIDs inhibit COX reducing PGE2 synthesis

Antipyretics effect

lower hypothalamic set point triggering vasodilation and sweating

Heat stroke

clinical thermoregulatory failure with impaired sweating and CNS dysfunction

Malignant hyperthermia

uncontrolled skeletal muscle metabolism causing hyperthermia

Hypothermia

clinical failure to generate or conserve heat

Thermoregulation in elderly

impaired vasomotor responses and reduced sweat gland activity

Thermoregulation in infants

high surface area to volume ratio and limited non-shivering thermogenesis

Infant risk

increased susceptibility to temperature extremes

Elderly risk

increased susceptibility to heat and cold stress

Clinical scenario fever in child

set point raised, shivering during chill, vasodilation and sweating during defervescence

Basal metabolic rate definition

energy expended at rest to maintain vital functions

Vital functions of BMR

circulation, respiration, cellular metabolism

Exercise effect on heat

voluntary increase in metabolic heat production

Shivering effect on heat

involuntary rhythmic muscle contractions increase heat

Catecholamines effect

increase metabolic rate and heat production

Thyroxin effect

long-term increase in basal metabolic rate

Cold shock response

immersion in ice water triggers hyperventilation and cardiovascular strain

Frostbite mechanism

freezing of skin and underlying tissues during extreme cold

Dehydration risk

common in desert and warm water immersion due to sweating

Muscle fatigue risk

seen in prolonged warm water immersion with activity

Clinical implication of fever

diagnostic marker of infection and inflammation

NSAIDs role

block COX enzyme reducing prostaglandin synthesis

Prostaglandin E2 role

mediates hypothalamic set point elevation in fever

Thermoregulatory failure consequences

heat stroke, hypothermia, malignant hyperthermia