What is the pathophysiology of tetanus?

Pathophysiology of Tetanus

Tetanus results from tetanospasmin, a potent neurotoxin produced by Clostridium tetani, which binds irreversibly to neural tissue and blocks the release of inhibitory neurotransmitters, causing uncontrolled muscle spasms and rigidity. 1

Causative Organism and Entry

• Clostridium tetani is a ubiquitous, spore-forming, motile Gram-positive anaerobic bacillus found in high concentrations in soil and animal excrement 1
• The spores enter the body through breaches in the skin or mucous membranes 1
• Germination of spores occurs only under anaerobic conditions, such as in necrotic tissue resulting from deep puncture wounds or blunt trauma 1
• Direct person-to-person transmission does not occur 1

Toxin Production and Mechanism

• Once germinated, C. tetani bacilli vegetate and produce tetanospasmin, a powerful exotoxin 1
• Tetanospasmin binds irreversibly with neural tissue 1
• The toxin prevents the release of inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the spinal cord, brainstem motor nuclei, and the brain 2
• This blockade of inhibitory neurotransmission produces muscle rigidity and tonic spasms of skeletal muscles 1, 2

Clinical Manifestations Based on Pathophysiology

Neuromuscular Effects

• Trismus (lockjaw) is typically the initial presentation, occurring in 75% of patients 3
• Dysphagia and laryngeal spasms result from involvement of cranial nerve nuclei 2
• Rigidity of limbs and paraspinal muscles with opisthotonic posture develops 2
• Reflex spasms occur in 70% of patients and characterize disease severity 3
• Frequent severe spasms can be triggered by touch, pain, bright light, or sounds, potentially producing apnea and rhabdomyolysis 2

Autonomic Dysfunction

• In severe tetanus, autonomic overactivity occurs, causing labile hypertension, tachycardia, increased secretions, sweating, and urinary retention 2
• Dysautonomia is difficult to manage and represents a common cause of mortality 2

Temporal Progression

• The incubation period from injury to symptom onset varies from 3 to 21 days (median: 7 days), with extremes of 1 day to several months 1, 4
• Shorter incubation periods are associated with more severe disease and poorer prognosis 1, 4
• Longer incubation periods are associated with injuries furthest from the central nervous system 1, 4
• The disease course is usually intense for ≥4 weeks before subsiding 1, 4

Critical Pathophysiologic Pitfall

The irreversible binding of tetanospasmin to neural tissue is the key pathophysiologic feature that explains why treatment focuses on neutralizing circulating toxin before it binds, rather than reversing already-bound toxin 1, 5. Once the toxin binds to neuronal cell membranes, recovery depends on regeneration of new nerve terminals, which explains the protracted convalescent period and potential for long-term neurologic sequelae 1, 4.

Mortality and Morbidity

• The case-fatality ratio can be as high as 100% without high-quality medical care, but remains approximately 10-20% even in modern healthcare facilities 1, 4
• The case-fatality ratio is highest in infants and the elderly 1, 4
• Long-term neurologic sequelae and intellectual and behavioral abnormalities may follow recovery 1, 4