Tetanus pathophysiology: Difference between revisions
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*The toxin uses retrograde transport along the axon to reach the spinal cord and the brainstem. | *The toxin uses retrograde transport along the axon to reach the spinal cord and the brainstem. | ||
*The toxins binds irreversibly with the receptors. | *The toxins binds irreversibly with the receptors. | ||
*The tetanus toxin cleaves the membrane proteins that are responsible for expulsion of substances at the neuron synapses. | *The tetanus toxin cleaves the membrane proteins ([[SNARE]] proteins) that are responsible for expulsion of substances at the neuron synapses. | ||
*This results in the alteration in the release of various [[neurotransmitters]] that cause inhibition. Leading to disinhibition. | *This results in the alteration in the release of various [[neurotransmitters]] that cause inhibition. Leading to disinhibition. | ||
*The disinhibition effects the neurons responsible for carrying motor cortex excitatory impulses effecting the autonomic neurons and the anterior horn cells. | *The disinhibition effects the neurons responsible for carrying motor cortex excitatory impulses effecting the autonomic neurons and the anterior horn cells. | ||
*The disinhibition involving anterior horn cells leads to an unopposed contraction of the muscles, leading to excessive tone and muscular spasm which can be painful. | *The disinhibition involving anterior horn cells leads to an unopposed contraction of the muscles, leading to excessive tone and muscular spasm which can be painful. | ||
*The autonomic nervous system when disinhibited can lead to a seizure. | *The autonomic nervous system when disinhibited can lead to a seizure. | ||
===Genetics=== | |||
The role of genetics in the development of tetanus has not been well established. | |||
*It is however believed that the formation of tetanus toxin is induced by the depletion of amino acids.<ref name="pmid27492724">{{cite journal| author=Licona-Cassani C, Steen JA, Zaragoza NE, Moonen G, Moutafis G, Hodson MP et al.| title=Tetanus toxin production is triggered by the transition from amino acid consumption to peptides. | journal=Anaerobe | year= 2016 | volume= 41 | issue= | pages= 113-124 | pmid=27492724 | doi=10.1016/j.anaerobe.2016.07.006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27492724 }} </ref> | |||
===Microscopic Pathology=== | ===Microscopic Pathology=== | ||
Revision as of 09:57, 24 May 2017
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
The bacteria that causes tetanus, Clostridium tetani is introduced into the human body usually by a wound. The toxins produced by the bacterium, utilize the blood and/or lymphatics to gain access to target tissues. The toxins can act at various places in the central nervous system, including the spinal cord, peripheral motor end plates, and the brain. They can also act on the sympathetic nervous system.[1][2]
Pathophysiology
Tetanus is caused by an exotoxin from Clostridium tetani that leads to acute, often fatal illness. Generalized, widespread rigidity and skeletal muscle spasms are common presentations of tetanus. The muscle stiffness begins from the jaw (lockjaw) progressing to the neck and then becoming generalized. C. tetani is a terminal spore forming bacteria. The spores is very resistant to extremes of temperature and to the normally used antiseptics. The spores can be found in the soil as well as in the intestines and feces of cattle, dogs, sheep, horses, cats, guinea pigs, rats, and chickens. The soil that has been treated with manure may contain huge amount of spores. Human adults related to agricultural work may also harbor the pathogen.
Pathogenesis
The pathogenesis of tetanus is as follows:[1][2][3][4][5]
- C. tetani gains access to the human body through a wound.
- The spores germinate, because of their anaerobic character.
- Toxins are produced and spread through the blood and lymphatics.
- C. tetani produces two exotoxins
- Tetanolysin, whose function is not well understood and
- Tetanospasmin, a metalloprotease, which is a neurotoxin responsible for the clinical picture of tetanus. Tetanospasmin is among the most potent toxins with respect to weight.
- The minimum lethal dose of tetanospasmin for humans, according to an estimate, is around 2.5 nanograms per kg of body weight or 175 nanograms for an individual who weighs 70-kg (154lb).
- The toxin uses retrograde transport along the axon to reach the spinal cord and the brainstem.
- The toxins binds irreversibly with the receptors.
- The tetanus toxin cleaves the membrane proteins (SNARE proteins) that are responsible for expulsion of substances at the neuron synapses.
- This results in the alteration in the release of various neurotransmitters that cause inhibition. Leading to disinhibition.
- The disinhibition effects the neurons responsible for carrying motor cortex excitatory impulses effecting the autonomic neurons and the anterior horn cells.
- The disinhibition involving anterior horn cells leads to an unopposed contraction of the muscles, leading to excessive tone and muscular spasm which can be painful.
- The autonomic nervous system when disinhibited can lead to a seizure.
Genetics
The role of genetics in the development of tetanus has not been well established.
- It is however believed that the formation of tetanus toxin is induced by the depletion of amino acids.[6]
Microscopic Pathology
References
- ↑ 1.0 1.1 Farrar JJ, Yen LM, Cook T, Fairweather N, Binh N, Parry J; et al. (2000). "Tetanus". J Neurol Neurosurg Psychiatry. 69 (3): 292–301. PMC 1737078. PMID 10945801.
- ↑ 2.0 2.1 Lalli G, Gschmeissner S, Schiavo G (2003). "Myosin Va and microtubule-based motors are required for fast axonal retrograde transport of tetanus toxin in motor neurons". J Cell Sci. 116 (Pt 22): 4639–50. doi:10.1242/jcs.00727. PMID 14576357.
- ↑ Rummel A, Bade S, Alves J, Bigalke H, Binz T (2003). "Two carbohydrate binding sites in the H(CC)-domain of tetanus neurotoxin are required for toxicity". J Mol Biol. 326 (3): 835–47. PMID 12581644.
- ↑ Schiavo G, Benfenati F, Poulain B, Rossetto O, Polverino de Laureto P, DasGupta BR; et al. (1992). "Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin". Nature. 359 (6398): 832–5. doi:10.1038/359832a0. PMID 1331807.
- ↑ Caccin P, Rossetto O, Rigoni M, Johnson E, Schiavo G, Montecucco C (2003). "VAMP/synaptobrevin cleavage by tetanus and botulinum neurotoxins is strongly enhanced by acidic liposomes". FEBS Lett. 542 (1–3): 132–6. PMID 12729912.
- ↑ Licona-Cassani C, Steen JA, Zaragoza NE, Moonen G, Moutafis G, Hodson MP; et al. (2016). "Tetanus toxin production is triggered by the transition from amino acid consumption to peptides". Anaerobe. 41: 113–124. doi:10.1016/j.anaerobe.2016.07.006. PMID 27492724.