What is the pathophysiology of tetanus?

Pathophysiology of Tetanus

Tetanus results from tetanospasmin, a powerful neurotoxin produced by Clostridium tetani that irreversibly binds to neural tissue and blocks the release of inhibitory neurotransmitters (GABA and glycine), causing uncontrolled muscle rigidity and spasms. 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. 2, 1
• Spores enter the body through breaches in the skin or mucous membranes, including puncture wounds, lacerations, burns, surgical sites, and umbilical stumps in neonates. 2, 1
• The disease is noncommunicable—direct person-to-person transmission does not occur. 2

Germination and Toxin Production

• Germination of spores occurs only under anaerobic conditions, such as in necrotic tissue resulting from deep puncture wounds or blunt trauma. 2, 1
• Once germinated, the vegetative bacilli multiply and produce tetanospasmin, a potent exotoxin. 2, 1
• Tetanospasmin is one of the most powerful biological toxins known. 3, 4

Toxin Mechanism and Neural Effects

• Tetanospasmin binds irreversibly to neural tissue, which is the critical pathophysiologic feature explaining why treatment focuses on neutralizing circulating toxin before binding rather than reversing already-bound toxin. 1
• The toxin enters the general circulation, binds to peripheral motor neurons and sensory neurons, and is transported retroaxonally to the spinal cord. 5
• Once in the central nervous system, tetanospasmin enters inhibitory interneurons and prevents the release of inhibitory neurotransmitters (GABA and glycine) in the spinal cord, brainstem motor nuclei, and brain. 1, 5
• This blockade of inhibitory neurotransmission produces unopposed excitatory signals, resulting in muscle rigidity and tonic spasms of skeletal muscles. 1, 3

Clinical Progression and Temporal Factors

• The incubation period varies from 3 to 21 days (median: 7 days), with extremes of 1 day to several months depending on wound severity and distance from the central nervous system. 2, 1, 6
• Shorter incubation periods are associated with more severe disease and poorer prognosis, as injuries closer to the central nervous system allow faster toxin transport. 2, 6
• Generalized tetanus typically presents with trismus (lockjaw), followed by generalized rigidity caused by painful contractions of skeletal muscles that can impair respiratory function. 2

Life-Threatening Complications

• Glottic spasm, respiratory failure, and autonomic instability (dysautonomia) can result in death. 2
• The syndrome of sympathetic nervous system overactivity is a serious late complication. 3
• 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. 2, 1, 6
• Mortality is highest in infants and the elderly. 2, 6

Important Clinical Pitfall

• Tetanus infection does not confer natural immunity because the amount of toxin required to cause disease is insufficient to stimulate an immune response, so patients must complete a full primary immunization series after recovery. 6, 7