Temperature regulation

The hypothalamic thermostat

• Anterior hypothalamus (preoptic area): heat-loss centre; senses warm blood; drives sweating and skin vasodilatation. Lesions cause hyperthermia.
• Posterior hypothalamus: heat-conservation and production centre; drives shivering, vasoconstriction and piloerection. Lesions cause poikilothermia (temperature drifts with the environment).
• Inputs: skin thermoreceptors (cold receptors outnumber warm ones) and central receptors sensing blood temperature in the hypothalamus, spinal cord and viscera.
• Core temperature is about 37 °C, with a circadian swing of about 0.5–1 °C: lowest in the early morning, highest in the late afternoon.
• After ovulation, luteal progesterone raises basal body temperature by about 0.3–0.5 °C (acting on the hypothalamus); the rise lasts until menstruation and is used to detect ovulation.
• Measuring core temperature: the most accurate continuous site under anaesthesia is the lower oesophagus (beside the heart and aorta); pulmonary artery blood is the reference standard; tympanic, nasopharyngeal and bladder sites are acceptable; rectal temperature lags behind rapid changes; oral and axillary readings are lower and less reliable.

Heat production

• Basal metabolism: the largest share at rest; raised by thyroid hormone and catecholamines.
• Muscle activity, especially shivering, which can raise heat production four- to five-fold but greatly increases oxygen consumption.
• Non-shivering thermogenesis in brown fat: uncoupling protein 1 (thermogenin) lets protons leak across the inner mitochondrial membrane so energy appears as heat instead of ATP. It is driven by sympathetic β3 stimulation and is vital in neonates, who cannot shiver effectively.
• Food: specific dynamic action, highest for protein.

Routes of heat loss

• Water conducts heat about 25 times faster than air and has a far higher heat capacity, so a person in water at 15 °C becomes hypothermic within an hour, whereas air at 15 °C is tolerated for many hours.
• Skin blood flow controls heat delivery to the surface. Skin of the hands, feet, ears and lips contains arteriovenous anastomoses under sympathetic adrenergic control. In heat they open, so skin flow can rise up to about 30% of cardiac output, far above metabolic need; this adds strain on a failing heart. In cold they close.
• Sweating is driven by sympathetic cholinergic fibres on muscarinic receptors, so anticholinergic drugs cause hot dry skin and hyperthermia. Sweat is hypotonic; a marathon runner who loses 2 L of sweat and replaces it with 2 L of plain water ends with a normal volume but low plasma sodium and osmolality.
• Alcohol dilates skin vessels: the drinker feels warm while losing heat rapidly, impairs shivering and judgement, and may cause hypoglycaemia, so drunk people exposed to cold become hypothermic.

Acclimatisation to heat

Over 1–2 weeks of exposure (for example, a soldier posted from a cool valley to Jacobabad in June):

• Sweating starts earlier and at a lower core temperature, and maximum sweat rate rises (up to about 2–3 L/h).
• Sweat sodium falls because aldosterone increases sodium reabsorption in the sweat duct, conserving salt.
• Plasma volume expands, and heart rate during work falls.
• These gains are lost within a few weeks of leaving the heat.

Fever (pyrexia)

• Exogenous pyrogens (lipopolysaccharide, other microbial products) or tissue injury activate macrophages.
• Endogenous pyrogens are released: IL-1, IL-6, TNF-α, interferons.
• These large proteins cannot cross the blood–brain barrier. They act at the organum vasculosum of the lamina terminalis (OVLT), a circumventricular organ with leaky capillaries, where endothelial COX-2 produces prostaglandin E2.
• PGE2 acts on preoptic neurons to raise the set point.
• Chill phase: body temperature is now below the set point, so the person feels cold, shivers (rigors) and has pale, vasoconstricted skin until core temperature reaches the new set point.
• Flush phase (crisis): when the stimulus settles, the set point falls; sweating and vasodilatation bring temperature down.
• Antipyretics (paracetamol, NSAIDs) inhibit COX and lower hypothalamic PGE2, resetting the set point. They do not work in heat stroke.
• Periodic fevers in malaria: fever coincides with synchronous rupture of red-cell schizonts, which releases parasite material and pyrogenic cytokines. *P. vivax* and *P. ovale* cause fever every 48 hours (tertian), *P. malariae* every 72 hours (quartan); *P. falciparum* is often irregular or continuous.

Postoperative fever

• Low rectal anastomoses carry the highest leak risk. Persistent or rising fever after 48 hours needs a search for infection.

Fever versus hyperthermia

Remember Fever is a thermostat turned up; heat stroke is a thermostat overwhelmed.

Heat illness and drug-induced hyperthermia

• Heat exhaustion: water and salt depletion; fatigue, headache, nausea, cramps; core temperature below about 40 °C; mental state normal.
• Heat stroke: core temperature above 40 °C with CNS dysfunction (confusion, seizures, coma). Classic (non-exertional) heat stroke in the elderly often has dry skin; exertional heat stroke in young people may still sweat. Complications: rhabdomyolysis, DIC, renal and liver failure. Rapid cooling by cold-water immersion or evaporative cooling.
• Malignant hyperthermia: autosomal dominant mutation of the ryanodine receptor (RYR1) of skeletal muscle sarcoplasmic reticulum. Volatile anaesthetics or suxamethonium cause uncontrolled calcium release, sustained contraction and hypermetabolism. Rising end-tidal CO₂, tachycardia and masseter rigidity come before the temperature rises. Treat with dantrolene, which blocks RYR1. Relatives need testing (muscle biopsy contracture test or genetics) and trigger-free anaesthesia.
• Neuroleptic malignant syndrome: antipsychotics (dopamine blockade); rigidity, high CK; dantrolene or bromocriptine.
• Serotonin syndrome: SSRIs with other serotonergic drugs; clonus, hyperreflexia; cyproheptadine.

Hypothermia

• Core temperature below 35 °C; mild 32–35, moderate 28–32, severe below 28 °C. Shivering stops below about 32 °C.
• ECG: bradycardia, J (Osborn) waves, prolonged intervals, atrial fibrillation, then VF or asystole.
• The cold myocardium is irritable: rough handling or sitting up can trigger VF, so move the patient gently and keep them horizontal. "Not dead until warm and dead": continue resuscitation while rewarming.
• Neonates and the elderly are at highest risk (large surface area relative to mass, reduced shivering).

Perioperative hypothermia

• First-hour fall (redistribution): anaesthesia abolishes tonic vasoconstriction, so heat moves from the warm core to the cooler periphery. This causes most of the early 1–1.5 °C fall even in a warm theatre; total heat content barely changes. Pre-warming the skin before induction reduces it.
• Later loss comes from radiation and convection, cold fluids and open body cavities.
• Why prevent it: postoperative shivering raises oxygen consumption (risky with coronary disease); cold impairs clotting enzymes and platelets, increasing bleeding; it also raises wound infection rates and slows drug metabolism.

Exam trap Hypothermia, acidosis and coagulopathy form the lethal triad in trauma; each worsens the others.

How FCPS asks about this

• Main route of heat loss at rest: radiation; only route in an environment hotter than skin: evaporation.
• Lying on the ground or immersed in water: conduction; water removes heat far faster than air.
• Endogenous pyrogens and their site of action: IL-1, IL-6, TNF act at the OVLT to make PGE2, which raises the set point.
• Change in sweat with acclimatisation: lower sodium (aldosterone), earlier and greater sweating.
• Rise in temperature after ovulation: progesterone, 0.3–0.5 °C.
• Malignant hyperthermia: autosomal dominant RYR1 defect; first sign rising end-tidal CO₂; treat with dantrolene.
• Early fall in core temperature after induction: redistribution of heat from core to periphery.

Exam trap Paracetamol does not help heat stroke, because the set point is normal.