Mechanisms by which normal body temperature is maintained and regulated

This chapter grapples with the scale of  Section R1(ii) of the 2023 CICM Primary Syllabus, which expects the trainees to "explain the mechanisms by which normal body temperature is maintained and regulated".  From the exam point of view, this topic enjoys an inflated importance, having appeared in the past papers numerous times:

Those past SAQs have sown confusion into the minds of the candidates by sampling all across the CICM exam vocabulary, variably asking the trainees to outline explain or list those mechanisms, and by changing expectations over time, such that to define the thermoneutral zone and inter-threshold range was expected in 2014, but attracted no marks in 2021. Still, the examiner's comments have been highly informative, as they reveal what was a part of the marking rubrics and give some idea to the trainee as to what they should prepare in their own notes. For example, normal values and the concept of peripheral and core body temperature seem to have been essential to the answers, and at one stage the examiners referred favourably to the "sensor, integrator, effector" method of discussing temperature regulation.  A mention of the normal physiological diurnal and menstrual variations was apparently a feature of the best answers. In summary, with such clear instructions to guide the author, it is nothing short of remarkable that the resulting chapters became so completely unhinged; but some remorseless emperor commanded him to take a winding path through detours into Gibbs free energy , evolution of vertebrates, and the thermodynamic characteristics of seal blubber. To rescue the reader from having to scroll through such an overgrowth of tangential material, this chapter is an attempt to identify and distill whatever scarce droplets that might have relevance for the CICM exams.

  • Mechanisms of heat production are metabolic chemical reactions that yield heat.
    • Breaking of high energy binds, eg. hydrolysis of ATP into ADP and Pi, yields chemical energy which is used to drive endothermic chemical reactions, but it is not utilised with 100% efficiency, and the residual energy is dissipated as heat.
  • Cellular reactions which produce heat, that are quantitatively important, are mostly localised to the mitochondria, and include:
    • Oxidation of NADH
    • ATP synthesis and the activity of the electron transport chain
    • Proton leak through mitochondrial inner membrane
    • Na+/K+ ATPase activity
    • Actin/myosin cross bridge cycling
  • Sites of thermogenesis are: 
    • Organs and tissues with a high baseline metabolic rate
      • Brain (60 kJ/hr)
      • Liver (60 kJ/hr)
      • Intestine (170 kJ/hr)
      • Heart (50 kJ/hr at rest) 
    • Organs and tissues with uncoupled mitochondria or scalable metabolic activity, which can increase their metabolic rate on demand:
      • Muscle (80 kJ/hr at rest, but up to five times more with shivering, and up to twenty times more with strenuous exercise) 
      • Brown adipose tissue (from 9 to 60 kJ/100g/hr)
    • Heat which is produced by these sites is homogenised across the total body mass mostly by convection via the blood (the thermal conductivity of tissues is otherwise too low for conductive heat transfer)
  • Core thermal compartment is the well-perfused body mass (~8% of total) which contains these highly metabolically active organs where most of the heat is generated.
  • Core temperature is a highly conserved stable temperature of the core compartment, which is carefully regulated by the hypothalamus
  • Peripheral temperature of the outer layers of tissue is lower and more variable
  • Thermoregulation is required to maintain temperature within a narrow range:
    • Normal body temperature is 37 °C for core temperature. 
      • Core temperature is a highly conserved stable temperature of the central compartment which contains highly metabolically active organs (brain, heart, liver, intestine) where most of the heat is generated.
      • Peripheral temperature of the outer layers of tissue is lower and more variable
    • Physiological variations in normal temperature follow predictable cycles:
      • Circadian:  core temperature varies by 1.0 °C during the day; maximum at 16:00-21:00 and minimum between 03:00 and 06:00.
      • Monthly ovulatory cycles: core body temperature is 0.3 °C to 0.7 °C higher in the post-ovulatory luteal phase
      • Ultradian fluctuations which appear to have a period of about 1 hour and a low amplitude of about 0.1 °C
      • Infradian fluctuations which are seasonal, with the core colder in winter by about 0.2 °C
    • Thermoneutral zone is the range of ambient temperatures where the body can maintain its core temperature solely through regulating dry heat loss by skin blood flow; 28-32 °C for a nude human and 14.8 °C - 24.5 °C for lightly clothed.
    • Lower critical temperature is the lower bound of the thermoneutral zone, below which facultative heat production is increased to maintain thermal balance.
    • Upper critical temperature is the upper bound of the thermoneutral zone, above which the thermal balance is maintained by sweating.
    • Core interthreshold zone: the range between core temperature at the onset of shivering and that at the onset of sweating, usually between 36.5 ºC and 37.5 ºC.
  • Temperature sensors can be divided into peripheral and central
    • Peripheral sensors are nociceptive neurons that express temperature-activated transient receptor potential (TTRP) cation channels; report to the hypothalamus via the lateral spinothalamic tract
    • Central sensors are temperature-sensitive neurons in the preoptic area of the hypothalamus, which sense core temperature 
  • The hypothalamus is the integrator for temperature sensation
    • Specifically the preoptic area of the hypothalamus
  • Thermoeffectors  are skin, skeletal muscle, sweat glands, and brown adipose tissue  
    • Non-shivering thermogenesis by muscle and brown adipose tissue mostly due to futile proton leak through the inner mitochondrial membrane which uncouples oxidative phosphorylation from ATP synthesis 
    • Shivering, involuntary muscle contractions which produce heat through the hydrolysis of ATP
    • Hypeventilation (and panting in animals), to increase evaporative heat loss via the upper respiratory tract 
    • Behavioural changes, eg. shelter or warmth-seeking, exercise 
    • Thermoeffector functions of the skin are the quantitatively important:
      • Cutaneous vasodilation and vasoconstriction is ​​​​​​​the mechanism for regulating the convective heat exchange between the core and the periphery.
      • This is mediated by: 
        • Centrally driven α1-mediated noradrenergic vasoconstriction
        • Translocation of  α2c adrenoceptors to the smooth muscle surface membrane, which is a local temperature-mediated  effect
        • Locally driven α1-mediated noradrenergic vasoconstriction (nerves talking to nerves, bypassing the central nervous system - this is a form of reflex neurogenic vasoconstriction)
        • Nitric oxide synthase inhibition, which occurs largely due to the effects of decreased temperature on that enzyme
      • By vasodilating, skin can increase to 50-70% of total cardiac output, increasing the convective heat exchange
      • This increases the efficiency of heat loss by convection, radiation, and evaporation of sweat.
      • Sweating  is quantitatively the most important - using the latent heat of vaporisation of sweat (2.4 kJ per gram of sweat at 30°C)
        • At maximum sweat production (~2000ml/hr), up to 1700W of heat can be dissipated under ideal conditions
      • Piloerection is of minimal importance in humans, but in furred mammals increases the thickness of the insulating air layer  

References