Question 4

Explain how a normal, healthy adult regulates their body temperature (70% of marks).

Explain how paracetamol exerts an antipyretic effect in a febrile patient (30% of marks).

[Click here to toggle visibility of the answers]

College Answer

Most candidates mentioned sweating, shivering, vascular response, and behavioural response
to cold environment. Outlining the requirements of the temperature sensors, control
processing area, and the effectors is, however, essential in order to pass this question. Most
candidates did not mention where the temperature sensors are and the possible hormonal
response to changes in the temperature of the environment. The interaction between
interleukin-1 (and other pyrogens) and prostaglandin production in the hypothalamus was
also not discussed.
Syllabus section L1.
Reference: Guyton & Hall 11th Edition page 894-901.

Discussion

  • Thermoregulation is a sensor-integrator-effector system
  • Sensors: 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 
  • Integrator is the preoptic area of the hypothalamus
  • Effectors are skin, skeletal muscle, sweat glands, and brown adipose tissue  
    • Skin vasodilation and vasoconstriction can alter skin blood flow to increase or decrease convection between core and periphery
    • Piloerection is of minimal importance in humans, but in furred mammals increases the thickness of the insulating air layer  
    • 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 
    • Sweating - quantitatively the most important - usuing the latent heat of vaporisation of sweat (2.4 kJ per gram of sweat at 30°C)

Paracetamol:

  • is a non-selective COX inhibitor, like NSAIDs
  • Interferes with the synthesis of PGE2 by cyclooxygenase in the CNS.
  • This interrupts the normal pyrogenic stimulation of the hypothalamus, which restores the temperature setpoint to normal levels

References

Aronoff, David M., and Eric G. Neilson. "Antipyretics: mechanisms of action and clinical use in fever suppression." The American journal of medicine 111.4 (2001): 304-315.

Mirrasekhian, Elahe, et al. "The antipyretic effect of paracetamol occurs independent of transient receptor potential ankyrin 1‐mediated hypothermia and is associated with prostaglandin inhibition in the brain." The FASEB Journal 32.10 (2018): 5751-5759.