Tetanus: Blocking the Release of Glycine and GABA
The correct pathophysiological mechanism is blocking the release of the neurotransmitters glycine and γ-aminobutyric acid (GABA). This patient's presentation—painful muscle spasms, facial sneer (risus sardonicus), stiff back (opisthotonus), clamped palms, and trismus (stiff jaw) following a penetrating nail injury one week prior—is classic for tetanus caused by Clostridium tetani infection 1, 2.
Pathophysiological Mechanism
Tetanus toxin (tetanospasmin) specifically blocks the release of inhibitory neurotransmitters glycine and GABA from presynaptic terminals in the central nervous system 2, 3. This mechanism occurs through the following sequence:
- The toxin undergoes retrograde intra-axonal transport from the wound site to the CNS 2
- The light chain of tetanus toxin functions as a zinc-dependent metalloprotease that cleaves synaptobrevin (VAMP), a vesicle-associated membrane protein essential for neurotransmitter release 2, 3
- By cleaving synaptobrevin, the toxin prevents vesicular fusion and blocks the release of glycine and GABA specifically 3
- This disinhibitory action creates unopposed excitatory neurotransmission, resulting in the characteristic muscle rigidity and reflex spasms 2
Clinical Correlation
The patient's symptoms directly reflect this pathophysiology 1, 4:
- Trismus (lockjaw) is the presenting symptom in 75% of tetanus cases 1
- Reflex spasms occur in 70% of patients and characterize disease severity 1
- Risus sardonicus (facial sneer), opisthotonus (stiff back), and generalized rigidity result from sustained muscle contraction without inhibitory control 4
- The typical 3-day to 3-week incubation period matches this patient's one-week timeline from injury to symptom onset 1
Why Other Options Are Incorrect
- ADP-ribosylation of elongation factor: This describes diphtheria toxin mechanism, not tetanus 2
- Blocking acetylcholine release: This is the mechanism of botulinum toxin, which causes flaccid paralysis, not the spastic paralysis seen here 3
- Pore-forming toxin: While some bacterial toxins work this way, tetanus toxin acts via metalloprotease activity on synaptic proteins 3
- Stimulation of adenylate cyclase: This describes cholera toxin mechanism, unrelated to neuromuscular symptoms 2
Critical Management Implications
This diagnosis requires immediate intervention 1, 4:
- Wound debridement to remove the anaerobic bacterial source 1
- Tetanus immunoglobulin to neutralize circulating toxin 5, 4
- Antibiotics (typically metronidazole or penicillin) 5
- Benzodiazepines (diazepam) to control muscle spasms by enhancing GABA activity 1, 5
- Airway management as laryngeal spasm can cause respiratory arrest 4
- ICU monitoring for autonomic instability and respiratory complications 1, 4
The high mortality risk (historically 76%, now 10-15% with proper treatment) emphasizes the importance of recognizing this clinical presentation early 1.