Fever and Hyperthermia

Thermoregulation Basics - Heat In, Heat Out

• Heat Gain (Thermogenesis):
  • Basal metabolic rate (BMR)
  • Muscular activity (exercise, shivering)
  • Hormonal: Thyroxine, catecholamines
  • Non-shivering thermogenesis (brown adipose tissue)
  • Specific Dynamic Action (SDA) of food
• Heat Loss (Thermolysis):
  • Radiation (~60% at rest)
  • Evaporation (sweat, insensible; ~22%)
  • Convection (~15%)
  • Conduction (~3%)
• Control: Hypothalamus (preoptic area) maintains core temp ~37°C.

⭐ Radiation is the major mechanism of heat loss from the body at rest in a thermoneutral environment, accounting for about 60% of total heat loss to surroundings cooler than the body.

Fever Pathophysiology - The Body's Hot Alarm

• Exogenous pyrogens (e.g., bacterial LPS, viruses) activate immune cells (macrophages, monocytes).
• Release endogenous pyrogens: cytokines like IL-1, IL-6, TNF-α.
• Cytokines act on hypothalamic OVLT (Organum Vasculosum Lamina Terminalis).
• Induce COX-2 enzyme → ↑ Prostaglandin E2 ($PGE_2$) synthesis.
• $PGE_2$ elevates hypothalamic thermoregulatory set-point.
• Body activates heat conservation (vasoconstriction) & production (shivering).
• Result: Core body temperature rises, causing fever.

⭐ Prostaglandin E2 is the principal mediator elevating the hypothalamic set-point in fever, acting on EP3 receptors.

Fever: Clinical & Management - Chill Pill Time

• Phases: Prodrome (malaise), Chill (shivering, vasoconstriction), Flush (sweating, vasodilation).
• Signs: Tachycardia (↑10 bpm/1°C rise), tachypnea, anorexia, delirium.
• Management:
  • Antipyretics: Paracetamol (DOC), NSAIDs (Ibuprofen). Mechanism: Inhibit COX → ↓$PGE_2$.
    • Aspirin: Avoid in children (Reye's syndrome).
  • Tepid sponging (avoid shivering).
  • Hydration & treat underlying cause.

⭐ Pulse-temperature dissociation (Faget's sign: fever with relative bradycardia) seen in Typhoid, Brucellosis, Yellow fever, Legionella, Mycoplasma.

Hyperthermia Explained - Not Just a Fever!

• Hyperthermia: Uncontrolled body temperature (BT) ↑, often >40°C (104°F).
  • Crucially, hypothalamic set point remains NORMAL.
• Contrast Fever: Set point is ELEVATED by pyrogens.
• Causes:
  • Environmental: Heat stroke (exertional/non-exertional).
  • Drugs: MDMA, Neuroleptic Malignant Syndrome (NMS), Malignant Hyperthermia (MH).
  • Endocrine: Thyrotoxicosis.
• Key: Antipyretics (e.g., paracetamol) are INEFFECTIVE as set point isn't raised.
• Management: Focus on rapid physical cooling.

⭐ Malignant Hyperthermia (MH) is a life-threatening hypermetabolic state triggered by specific anesthetics (e.g., halothane, succinylcholine); treat urgently with dantrolene.

Hyperthermic Syndromes - Crisis Control

• Heat Stroke: Rapid cooling (evaporative/ice packs), IV fluids. Target core temp <39°C.
• Malignant Hyperthermia (MH): Anesthetic trigger (e.g., halothane, succinylcholine).
  • Rx: Dantrolene (2.5 mg/kg IV), stop trigger, active cooling.
• Neuroleptic Malignant Syndrome (NMS): Antipsychotic trigger. 📌 Mnemonic: FEVER.
  • Rx: Stop agent, dantrolene, bromocriptine, cooling.
• Serotonin Syndrome: Serotonergic agent trigger (e.g., SSRIs, MAOIs).
  • Rx: Stop agent, cyproheptadine, supportive care, cooling.

⭐ Dantrolene for Malignant Hyperthermia: 2.5 mg/kg IV. It is life-saving by inhibiting calcium release from muscle stores (sarcoplasmic reticulum).

High‑Yield Points - ⚡ Biggest Takeaways

• Fever: Cytokines (IL-1, TNF-α) ↑ PGE₂ in hypothalamus, raising set point.
• Hyperthermia: Set point normal; heat dissipation fails.
• Aspirin: ↓ PGE₂ by COX inhibition, reducing fever.
• Malignant Hyperthermia: RYR1 mutation; triggered by halothane, succinylcholine; treat with dantrolene.
• Heat Stroke: Core temp > 40°C, CNS dysfunction, often anhidrosis.
• NMS: Antipsychotics; rigidity, fever; treat with dantrolene, bromocriptine.
• FUO: Temp > 38.3°C > 3 weeks, undiagnosed after 1 week investigation.