Pathophysiology of Tetanus

       How can Clostridium Tetani attack human body? let's discuss pathophysiology of tetanus. Clostridium tetani enter the human body through wounds usually in the form of spores. This Disease appears when spores grow into vegetative forms that produce tetanospasmin on the state of low oxygen tension, tissue necrosis or oxygen reduction potential.

Toxin released by Clostridium tetani spread in various ways, as the following:

1. Entry into the muscle
Toxin into the muscles that lie beneath or around the wound, and then to the surrounding muscles and so on in ascending through the synapse into the central nervous system.

2. Spread through the lymphatic system
Toxins which are in the tissue will be quickly entered into the node lymph, then through the lymphatic system into the systemic blood circulation.

3. Spread into the blood vessels.
Toxin into the blood vessels mainly through the lymphatic system, but can also through the capillary system around the wound. Spread through the blood vessels is an important way not even determine the severity of the disease. In humans most of the toxin is absorbed into the blood vessels, making it possible to be neutralized or arrested by administration of the optimal dose of antitoxin given intravenously. Toxin does not enter the central nervous system via the blood circulation because it is difficult to penetrate the brain barrier. Something that is very important is the toxin can spread to other muscles even to other organs through the bloodstream, thus indirectly increasing toxin transport to the central nervous system.

4. Toxin entry into the central nervous system (CNS)
Toxin entry into the CNS by spreading through nerve fibers. In retrograde, the toxin reaches the CNS through the nervous system motor, sensory and autonomic. Toxins that reach the anterior horn spinal cord or brainstem motor nuclei then joined the presynaptic receptors and neural inhibitors.

Relationships between clinical manifestations with the spread of the toxin

• Local  Tetanus
In this form, patients usually have antibodies to the tetanus toxin into the blood, but not enough to neutralize the toxins that are in around the wound.

• Cephalic Tetanus
Local tetanus is a form that follows trauma to the head. Affected muscles are the muscles that are innervated by the motor nuclei of the brain stem and cervical spinal cord.

•  Ascending Tetanus
A form of tetanus disease that usually begins in the form of the local limb and then spread throughout the body. After the local tetanus, toxin around the entry wound is pretty much the way ascending into the CNS.

•  General Tetanus
In this situation toxins through the blood circulation into the various muscles and then enter into the CNS. The disease is usually preceded trismus later muscles on the face, neck, body and extremities final. This is due to the long neural system every place is different, which is the shortest care of the jaw muscles, then sequentially on other areas in accordance long sequence of nerve.


1. toxin type
Clostridium tetani produces tetanolisin and tetanospasmin. Tetanolisin have hemolisin and protease effect, at high doses raises cardiotoxic and neurotoxic effects. Until now tetanolisin role in human tetanus is not known for sure. Tetanospasmin have neurotoxic effects, research on the pathogenesis of tetanus toxin is particularly connected with.

2. Tetanus toxin and receptors on neural networks
Tetanus toxin associated with the tip ganglioside presynaptic membranes, both at neuromuscular junction, or in the central nervous system. This bond is important for the transport of toxins through nerve fibers, but the relationship between binding and toxicity is not known clearly. Lazarovisi et al (1984) could identify two forms of tetanus toxin A toxin are less have the ability to binds to nerve cells but still has antigenicity and biotoxicity effects, and a powerful toxin B binds to nerve cells.

3. Tetanus toxin on neurotransmitters work
The main workplace toxins are at the synapse inhibition of central nervous system, ie the way to prevent the release of neurotransmitters inhibition, such as; glycine, Gamma Amino Butyric Acid (GABA), dopamine and noradrenaline. GABA is neuroinhibitor most major central nervous system, which works to prevent the release of nerve impulses excessif. Tetanus toxin does not prevent the synthesis or storage of glycine or GABA, but specifically inhibited the release of both neurotransmitters in the synapse region dangan way influence the sensitivity of calcium and exocytosis process.


1. Central nervous system
       Inhibitory effects on the state of the outbreak raises presinap electricity constantly referred to as generators of pathological Enhance excitation. This situation raises the flow of impulses with a high frequency of CNS to the peripheral, causing muscle stiffness and spasms. The more neural inhibition
exposed to increasingly severe seizures that occur. Stimuli such as sound, emotion, and light touch can trigger seizures because motorneuron in the spinal cord associated with neural networks such as reticulospinal. Sometimes found when seizure free (interval), it is probably because not all affected nerve toxin inhibition, there are some that are resistant to the toxin.
• Pain
The pain arises from muscle stiffness and spasms. Sometimes found severe neurotic pain in local tetanus even in the absence of seizures. The pain is presumably because the effect of toxins on the posterior ganglion nerve cells, the cells in the posterior horn and interneurons.
• Function Sublime
Awareness of patients in general good. On those who are not aware of is usually related to how big the effect of toxins on the brain, how much effect hypoxia, metabolic disorders and given sedatives or anticonvulsants.

2. Peripheral neuromuscular activity
        Tetanus toxin causes a decrease in acetylcholine release that has neuroparalisis effect, but this effect is masked by the inhibitory effects on the central nervous system. Neuroparalytic can happen when the effects of the toxin to the CNS does not happen, but this is difficult because the toxin quickly spread to the CNS. Neuroparalytic effects sometimes seen in cephalic tetanus, which is paralysis of the facial nerve, it may n.fascialis more sensitive to the effects of a paralytic toxin or because axonopathi.
Another effect of tetanus toxin on peripheral neuromuscular activity in the form of:
• Peripheral neuropathy
• miostatic contracture can be muscle stiffness, muscle movement
limited and the pain, which may occur several weeks to several months
after recovery.
• Partial denervation of specific muscles.

3. Changes in the autonomic nervous system
        On tetanus fluctuations of sympathetic system activity, and the parasympathetic, this may occur due to an imbalance of the two systems. The mechanism of autonomic system dysfunction due to the effects of toxins from muscles (retrograde) and results dissemination intraspinalis (from anterior horn, to the lateral horn of the spinal cord thoraxal). Autonomic system disorders can occur in general on various organs such as the cardiovascular, gastrointestinal, bladder, temperature control function and bronchial muscle control, but it may be only on one particular organ.

4. Respiratory System Disorders
        Respiratory system disorders can be caused by:
a. Stiffness and hipertonus of the intercostal muscles, body and abdomen; muscle of diaphragm is exposed to the end. Thorax wall stiffness, especially when seizures are happen very often result in limited movement of the chest cavity that disturb the ventilation. Tetanus often lead to severe respiratory failure characterized by hypoxia and hypercapnia. However tachypnea may occur due to excessive activity of nerves in the central neural effects that are not affected by the toxin.
b. Inability to remove secretions trachea and bronchi due to pharyngeal muscle spasm and stiffness and an inability to cough and swallow properly. So there is a high risk for the occurrence of which can lead to aspiration pneumonia, bronchopneumonia, and atelectasis.
c. Pulmonary microcirculation disorders
Abnormalities in the lung can be determined even in the incubation period. Abnormalities that can occur in the form of pulmonary vascular congestion, hemorrhagic pulmonary edema and ARDS. ARDS may also occur because of the iatrogenic or systemic infections such as sepsis following tetanus.

d. Central respiratory disorders
      Patients with decreased resistance to asphyxia. Clinical observation indicate suspicion of involvement in patients with tetanus respiratory center are:
- The episode of respiratory distress due to severe difficulty in breathing without reveal any pulmonary complications, bronchospasm and increased secretions in the airway. The episodes vary in a few minutes to ½ -1 hour.
- The apnoeic spells, these signs usually progress to prolonged respiratory arrest (stopping breathing prolonged) and eventually died.
- Stop breathing acute and sudden death.
Notwithstanding the foregoing, the central respiratory disorders caused by hypoxia secondary causes such as recurrent / persistent, long or asphyxia due to laryngospasm seizures, respiratory distress hypocapnia after the attack, and the result of acid-base balance disorders.

5. Hemodynamic disturbances
Cardiovascular system instability found in patients with tetanus with autonomic nervous system disorders are severe.

6. Metabolic disorders
      Metabolic rate in tetanus were significantly increased due to seizures, increased muscle tone, excessive activity of the sympathetic nervous system and hormonal changes. Oxygen consumption increased, in some cases it can be reduced by giving relaxans muscle. Various experiments showed an increase in urea excretion nitogen, plasma and urinary catecholamines, and decreased serum albumin protein fractions especially.
      Increased catecholamines increase metabolic rate, oxygen intake when can not meet these needs, such as problems with the respiratory system to hypoxia, there will be consequences. Severe protein catabolism, protein insufficiency and hypoxia will lead to anaerobic metabolism and reduce the formation of ATP, the state will reduce the ability of the immune system to recognize antigens causing toxin as insufficient antibody formed. This phenomenon may explain why the tetanus patients who had recovered, no / less immunity to the toxin found.

7. Hormonal Disorders
       Disruption to the hypothalamus or brainstem-hypothalamic pathway is suspected in patients with severe tetanus on the basis of the discovery of episodes of acute hyperthermia and fever without reveal any secondary infection. Increased alertness and awareness raises allegations of brainstem reticular activity is excessive. Of the hypothalamic-pituitary axis, containing specific nerve fibers that stimulate hormone secretion. Secretory activity of the nerve fibers is modulated by monoamine neurons locally. A decrease in levels of prolactin, TSH, LH and FSH were suspected because of the constraints of the feedback mechanism pituitary-endocrine gland.

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