Hyperthermia and malignant hyperthermia – etiology, pathogenesis, and clinical manifestations.
Hyperthermia
Hyperthermia is an uncontrolled increase in body temperature, without a change in hypothalamic set point.
- Unlike fever, it results from excessive heat production or impaired heat loss.
Etiology (Causes)
- 1 Excessive heat production
- Strenuous exercise (especially in hot environments).
- Seizures or severe muscle activity (e.g., status epilepticus).
- 2 Impaired heat loss
- High environmental temperatures and humidity (heat stroke).
- Dehydration → reduced sweating.
- Wearing heavy clothing.
- 3 Drug-induced
- Anticholinergic drugs (e.g., atropine) → inhibit sweating.
- Sympathomimetics (e.g., amphetamines) → increase metabolism.
Pathogenesis
- Excessive heat generation and/or reduced dissipation overwhelm thermoregulatory mechanisms.
- No adjustment of hypothalamic set point (contrast with fever).
- Core temperature can exceed 40°C, leading to cellular protein denaturation and enzyme dysfunction.
- Circulatory collapse may occur due to dehydration and vasodilation.
Clinical Manifestations
- Hot, dry skin (especially in classic heat stroke).
- Severe dehydration.
- Confusion, delirium, loss of consciousness.
- Tachycardia, hypotension.
- Multiorgan dysfunction (liver, kidneys, brain).
Malignant Hyperthermia
A genetic pharmacogenetic disorder, characterized by a rapid, life-threatening hypermetabolic state triggered by certain anesthetic agents.
Etiology (Causes)
- Triggered by volatile anesthetic gases (e.g., halothane, sevoflurane) or succinylcholine.
- Genetic predisposition: mutation in RYR1 gene encoding the ryanodine receptor in skeletal muscle.
Pathogenesis
- Mutated ryanodine receptor → excessive release of calcium from sarcoplasmic reticulum in skeletal muscle.
- Uncontrolled muscle contraction → massive increase in metabolic rate.
- Excessive ATP consumption, heat production, and lactic acidosis.
- Hyperkalemia from muscle breakdown (rhabdomyolysis).
Clinical Manifestations
- Rapid increase in body temperature (can exceed 41°C).
- Generalized muscle rigidity (especially masseter muscle).
- Tachycardia, arrhythmias (due to hyperkalemia).
- Metabolic acidosis.
- Myoglobinuria (brown urine due to muscle breakdown).
- Hypercapnia (high CO₂ levels).
Treatment (Key Points)
Hyperthermia
- Rapid cooling (cold IV fluids, ice packs).
- Rehydration and electrolyte correction.
Malignant Hyperthermia
- Immediate administration of dantrolene sodium (inhibits calcium release from sarcoplasmic reticulum).
- Cooling measures.
- Manage metabolic derangements (acidosis, hyperkalemia).