Botulism pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Michael Maddaleni, B.S.
Overview
Botulism is most commonly caused by neurotoxins produced by C. botulinum. but C. baratii produces similar neurotoxins (5, 6). The neurotoxins which cause botulism are the most potent toxins currently known and cause paralysis through the inhibition of acetlylcholine release in human nerve endings. Clostridium botulinum is an obligate anaerobe that forms spores.
Pathophysiology
Botulism is most commonly caused by neurotoxins produced by C. botulinum, but C. baratii produces similar neurotoxins (5, 6). These toxins have been designated by letters, and human botulism has been caused by toxins A, B, E, and F.
The neurotoxins which cause botulism are the most potent toxins currently known and cause paralysis through the inhibition of acetlylcholine release in human nerve endings
Symptoms may begin as a headache and vomiting and progress to proximal and then distal paralysis (6). Eventually respiratory failure may occur due to paralysis and the morality rate for botulism is currently only 3 to 5 percent, in part due to mechanical respiration technology
The video presented here is of Botulinum toxin B and provides a general overview of the cause of Botulism. It describes the mechanism of action that the toxin takes within the nerve cells.
Clostridium botulinum is an obligate anaerobe that forms spores. The natural habitat for the Clostridium botulinum spores is the soil. The species of Clostridium botulinum is made up of 4 genetically diverse groups that do not have much in common other than the fact that they all produce the botulinum toxin.[1] The botulinum toxin itself exists as 7 different antigenic types and these 7 antigenic types have been assigned a series of letters: A, B, C, D, E, F, G.[1] These toxins have a specific definition, and they are defined by their inability to cross neutralize the other types. For example, Anti-A toxin can not neutralize any of the other toxin types (B-G). It should be noted that Clostridium baratii and Clostridium butyricum can also produce the botulinum toxin.[1]
The botulinum molecule itself is composed of a heavy chain as well as a light chain polypeptide. It is referred to as a dichain polypeptide. The light chain of the toxin contains an endopeptidase that blocks acetylcholine-containing vesicles from being able to fuse with the membrane at the end of the motor neuron. If acetycholine is not present, it will result in flaccid muscle paralysis.[1]
Many people may not realize it, but the commercial therapeutic procedure termed "Botox" actually contains the botulinum toxin. However, there is a very small amount of it present, otherwise it would present an extensive danger. A vial of type A preparation, which is currently licensed in the US, contains only about 0.005% of the lethal oral dose and 0.3% of the lethal inhalation dose.[1]
Clostridium botulinum is divided into 4 groups:
- Group I - can produce toxins specifically A, B, or F proteolytic
- Group II - can produce toxins specifically B, E, or F, nonproteolytic
- Group III - can produce toxins C or D
- Group IV - can produce toxin G but toxin G has not been shown to cause neuroparalytic illness.
Honey, corn syrup, and other sweeteners are potentially dangerous for infants. This is partly because the digestive juices of an infant are less acidic than older children and adults, and may be less likely to destroy ingested spores. In addition, young infants do not yet have sufficient numbers of resident microbiota in their intestines to competitively exclude C. botulinum. Unopposed in the small intestine, the warm body temperature combined with an anaerobic environment creates a medium for botulinum spores to germinate, divide and produce toxin. Thus, C. botulinum is able to colonize the gut of an infant with relative ease, whereas older children and adults are not typically susceptible to ingested spores. C. botulinum spores are widely present in the environment, including honey. For this reason, it is advised that neither honey, nor any other sweetener, be given to children until after 12 months. Nevertheless, the majority of infants with botulism have no history of ingestion of honey, and the exact source of the offending spores is unclear about 85% of the time. Spores present in the soil are a leading candidate for most cases, and often a history of construction near the home of an affected infant may be obtained.
Gross Pathology
Shown below is an image of contaminated Jalapeño peppers involved in an outbreak of botulism in Pontiac, Michigan, April, 1977. Ingestion of botulinal toxin results in an illness of variable severity. Common symptoms are diplopia, blurred vision, and bulbar weakness. Symmetric paralysis may progress rapidly. This is a close up of contaminated Jalapeño peppers involved in an outbreak of botulism in Pontiac, Michigan, April, 1977. Ingestion of botulinal toxin results in an illness of variable severity. Common symptoms are diplopia, blurred vision, and bulbar weakness. Symmetric paralysis may progress rapidly.
Shown below is an image of Clostridium botulinum Type E colonies displaying an opaque zone grown on a 48hr egg yolk agar plate; Mag. 1.9 C. botulinum Type E is an indigenous organism in the aquatic environment, and is the type mainly associated with botulism from seafood products. It is a Gram-positive, anaerobic, -forming food borne pathogen.
Shown below is an image of this is a Clostridium botulinum type A colony grown on a 72 hour blood agar plate; Magnification 5X. The bacterium C. botulinum produces a nerve toxin, which causes the rare, but serious paralytic illness Botulism. There are seven types of botulism toxin designated by the letters A through G; only types A, B, E and F cause illness in humans.
Shown below is an image of Clostridium botulinum type A colonies, Strain 2, grown on a 48hr blood agar plate. The bacterium C. botulinum produces a nerve toxin, which causes the rare, but serious paralytic illness Botulism. There are seven types of botulism toxin designated by the letters A through G; only types A, B, E and F cause illness in humans.
Shown below is an image of wound botulism involvement of compound fracture of right arm. 14-year-old boy fractured his right ulna and radius and subsequently developed wound botulism.
Shown below is an image of six week old infant with botulism, which is evident as a marked loss of muscle tone, especially in the region of the head and neck.
Microscopic Pathology
Shown below is an image of gram-stained micrograph of Clostridium botulinum Type-A in thioglycollate broth was incubated for 48hrs at 35°C. C. botulinum is the bacterium responsible for the condition known as botulism, producing a neurotoxin the effects of which may be neutralized by various therapeutic agents.
Shown below is an image of Clostridium botulinum spores stained with Malachite Green Stain. The endospores of C. botulinum when stained using the Malachite Green staining method will appear as green spheres, while the bacilli themselves will turn purple in color.
References
- ↑ 1.0 1.1 1.2 1.3 1.4 Arnon SS, Schechter R, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Fine AD, Hauer J, Layton M, Lillibridge S, Osterholm MT, O'Toole T, Parker G, Perl TM, Russell PK, Swerdlow DL, Tonat K (2001). "Botulinum toxin as a biological weapon: medical and public health management". JAMA : the Journal of the American Medical Association. 285 (8): 1059–70. PMID 11209178. Retrieved 2012-02-16. Unknown parameter
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