Therm – Regulation

Master answer

Definitions

• Temperature – average kinetic energy of the atoms and molecules that make up a substance
• Temperature setpoint is the level at which the body attempts to maintain its temperature.
• Core body temperature:
  • Refers to deep body temperature of main internal organs (in head, trunk, abdomen) →
    sites where metabolic activity occur (Ie. heat production)
  • Kept constant at 37 +/- 0.4 °C (“Normothermia”) → displays normal variations:
    • Diurnal variation – ↑ in evening (37.3 °C) and ↓ in early morning (35.8 °C)
    • Menstrual variation – ↑ 0.5 °C in latter half of cycle
• Variations in core body temperature:
  • Normothermia → core body temperature 37 +/- 0.4 °C
  • Hypothermia → core body temperature < 36 °C
  • Hyperthermia → core body temperature > 37.5 °C
• Peripheral body temperature:
  • Refers to body temperature peripherally (Ie. skin, arms, legs, superficial tissues of core
    sites) → sites where heat loss occur
  • Temperature varies widely → always LESS than core body temperature
• Regulation of body temperature is done by balancing heat loss and heat production, predominantly through behavioural mechanisms and skin

Regulation of Body Temperature

Temperature sensors are central and peripheral, whilst regulation occurs centrally, and has multiple
effectors

Sensors:

• Central
  • Deep tissues/viscera (Eg. in intestinal wall)
  • Brain (anterior hypothalamus and extra-hypothalamic areas)
  • Spinal cord
• Peripheral
  • Dermis (main)
  • Corneas

Central Controller:

Hypothalamus is the main body temperature regulatory centre

• Posterior hypothalamus responds to cold
  • inputs from peripheral afferents
  • responsible for the temperature set point
  • ACh is the major neurotransmitter here.
• Anterior hypothalamus responds to heat
  • both peripheral input and change in blood temperature
  • Major neurotransmitters are Nad, 5HT, dopamine and prostaglandins.

Effector Mechanisms:

1. Skin
   • Sweating (evaporation)
     • Secrete plasma-like fluid Na142, Cl- 104 (urea/K, etc v low amounts) osmolality controlled by rate of secretion and aldosterone
     • loss via evaporation (latent heat of vapourisation of water)
     • 1-2L in extreme exercise up to 10 L max per 25 hours.
     • 0.54 kcal/gram of H2O evaporated
     • Degree of evaporation determined by ambient temperature and relative humidity
   • Blood Flow (radiation)
     • 8 (300 mL/min) – 30% CO skin
     • Vasodilation up to 30 fold increase
     • Vasoconstriction up to 10 fold decrease
     • vasoconstriction/dilation controlled by SNS (α1-mediated) vascular SM contraction and hypothalamic feedback
   • Fat/Clothing
     • Fat conducts heat 1/3 as readily as other tissues (decreased radiation)
     • Clothes reduce conductive heat loss via private zone of air adjacent to skin and decreased convection air currents -50% and more if specialised
2. Non-Skin
   • Non-shivering thermogenesis
     • Predominantly in brown fat
     • Uncoupling of oxadative phosphorylation
     • Increased heat gain without oxygen consumption/ATP production
   • Shivering
     • Increased heat gain by metabolism
   • Behaviour
     • For gain (exercise) or loss (submerging in water)
     • Voluntary muscle contraction (Ie. ↑ activity with cold stress; ↓ with hot stress) – Affects heat production
     • Body posturing (Ie. ↓ BSA with cold stress;↑ with hot stress) – Affects heat loss
     • Clothing (Ie. ↑ clothing with cold stress; ↓ with hot stress) – Affects heat loss
   • Appetite
     • Cold stress stimulates food-induced thermogenesis → ↑ metabolic rate and heat production
   • Thyroid hormone secretion
     • Cold stress stimulates thyroid hormone secretion → long-term ↑ metabolic rate and heat production

Gladwin / JC 2019

Paracetamol antipyresis

• Class: It is an acetanilide derivative used as Analgesic/Antipyretic
• MOA is poorly understood

• Likely via prostaglandin synthesis inhibition, serotonergic and cannabinoid pathways.
• Inhibits COX isoenzymes (COX-1 and COX-2) in areas of low inflammation.
• Inflammation → IL1, IL6, TNF, prostaglandin formation → fever
• Antipyretic Effect
  • CNS PG-E synthesis inhibition in anterior hypothalamus

Gladwin / JC 2019

Answer by Gladwin, JC