PATHOGENESIS

Tetanus occurs when spores of Clostridium tetani, an obligate anaerobe normally

present in the gut of mammals and widely found in soil, gains access to damaged
human tissue. After inoculation, C. tetani transforms into a vegetative rod-shaped
bacterium and produces the metalloprotease tetanus toxin (also known as
tetanospasmin).

After reaching the spinal cord and brainstem via retrograde axonal transport within the
motor neuron, tetanus toxin is secreted and enters adjacent inhibitory interneurons,
where it blocks neurotransmission by its cleaving action on the membrane proteins
involved in neuroexocytosis. The net effect is inactivation of inhibitory
neurotransmission that normally modulates anterior horn cells and muscle contraction.
This loss of inhibition (ie, disinhibition) of anterior horn cells and autonomic neurons
results in increased muscle tone, painful spasms, and widespread autonomic instability.

Muscular rigidity in tetanus occurs though a complex mechanism that involves an

increase in the resting firing rate of disinhibited motor neurons and lack of inhibition of
reflex motor responses to afferent sensory stimuli. Lack of neural control of adrenal
release of catecholamines induced by tetanus toxin produces a hypersympathetic state
that manifests as sweating, tachycardia, and hypertension.

Tetanus toxin-induced effects on anterior horns cells, the brainstem, and autonomic
neurons are long lasting because recovery requires the growth of new axonal nerve
terminals.

The mechanisms of binding to and inhibition of neural cells are related to specific
portions of the tetanus toxin molecule. Tetanus toxin is produced initially as an inactive
polypeptide chain by actively growing organisms. This synthesis is controlled by genes
located in an intracellular plasmid.

After the toxin is released, it is activated by bacterial or tissue proteases into its active
form, which contains a heavy chain necessary for binding and entry into neurons and a
light chain responsible for its toxic properties. Heavy chains are further cleaved by
pepsins into specific fragments, which individually mediate binding to specific types of
neural cells. Presynaptic inhibition of neurotransmitter release is mediated via light
chains.

Tetanolysin is another toxin produced by C. tetani during its early growth phase. It has
hemolytic properties and causes membrane damage in other cells, but its role in clinical
tetanus is uncertain.

Predisposing factors — Because C. tetani will not grow in healthy tissues, a

convergence of factors must be present in order for tetanus toxin to be elaborated in the
human host. This combination of factors usually includes absence of antibodies (ie,
from inadequate vaccination) plus two or more of the following:
 ●A penetrating injury resulting in the inoculation of C. tetani spores
●Coinfection with other bacteria
●Devitalized tissue
●A foreign body
●Localized ischemia

The above factors explain why tetanus-prone injuries include splinters and other
puncture wounds, gunshot wounds, compound fractures, burns, and unsterile
intramuscular or subcutaneous injections (that often occur in injection drug users).
These predisposing factors can also explain why tetanus can develop in unusual clinical
settings such as in:

●Neonates (due to infection of the umbilical stump)

●Obstetric patients (after septic abortions)
●Postsurgical patients (with necrotic infections involving bowel flora)
●Adolescents and adults undergoing male circumcision in sub-Saharan Africa
●Patients with dental infections
●Diabetic patients with infected extremity ulcers
●Patients who inject illicit and/or contaminated drugs

Tetanus in patients without an identifiable cause — An identifiable antecedent

cause for tetanus is obvious in most patients presenting with tetanus, but no cause can
be identified in up to a quarter of patients with classic signs and symptoms of tetanus.
Presumably, minor unnoticed abrasions or skin injuries are responsible for most or all of
these "cryptogenic" cases. Tetanus has occurred rarely in patients who have received a
timely and correct series of tetanus immunizations