lecture 13 gregg
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| situations in the US where ppl still get tetanus | 70% following injury, elderly women with waning immunity or inadequate adult immunizations, "skin-popping" black tar heroin users, body piercings
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| progenitor tetanus neurotoxin | light chain - toxic moiety (strongly homologous with botulinum toxin) binds peripheral nerves and travels retrograde to GABA and glycinergic interneuron terminals // heavy chain is cleaved from light chain - cell receptor specificity @ neuron target
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| tetanus neurotoxin | Zn-dependent endopeptidase cleaves synaptobrevin to prevent NT release by descending inhibitory neurons = continuous contraction of antagonist muscles = muscular rigidity and hypersympathetic state
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| signs and sx of generalized tetanus aka spastic paralysis | afebrile, trismus, risus sardonicus, abd rigidity, opisthotonus, resp compromise, severe pain all while being completely mentally alert
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| cephalic tetanus | from head or neck wound, involves the CN musculature predominantly. facial paralysis can lead to generalized tetanus
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| accidental umbilical stump inoculation leads to: | generalized tetanus in neonates, esp. whose mother's weren't adequately immunized. high mortality rate from sepsis
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| DDx for trismus or tetanus-like rigidity | electromyography and spatula test to confirm true tetanus. o/w: metoclopramide or phenothiazine-induced dystonia or dental abscess
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| tx for tetanus | maintain airway & feeding tube for hypernutrition, keep room quiet and dark, benzodiazepines IV or intrathecal baclofen, NMJ blockers, passive and active immunization to tetanus, metronidazole and wound debridement, labetalol IV or morphine & heparin
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| populations that require Tdap booster | preg women, those in close contact with neonates and infants, adults > 65 y/o
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| cases in which one receives human tetanus Ig via IM route and tetanus toxoid booster via another IM site | if fresh contaminated wound in pt with inadequate immunization hx OR pts who clinically have tetanus
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| unique feature about C. botulinum in cx | grows on egg yolk agar and is lipase (+) so it leaves a clear halo around the colonies
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| primary mechanism for botulism in US | ingestion of spores in home-canned foods or fruits or fish products with pH > 4.6 or eating meat/blubber in Alaska
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| specific cases where wound botulism risk goes way up | "skin popping" black tar heroin use, intranasal cocaine use, dental abscesses, major traumas
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| botulinum toxin | resembles tetanospasmin, is the single most poisonous substance known on earth. forms A, B, E & F are most often seen in foods and cause human infections.
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| subtypes of botulinum toxin seen in drug users | A and B - they will only have wound botulism and no GI sx
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| infant botulism | the most frequently encountered form in the US. due to colonization of the gut by the clostridia and then production of the toxin in vivo.
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| pathogenesis of botulinum toxin | attaches to cholinergic ganglionic and parasympathetic synapses and NMJs via the heavy chain // light chain separates and is a Zn-containing enzyme that, depending on serotoxiciity cleaves 1 of 3 enzymes
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| 3 enzymes affected by botulinum toxin | SNAP-25, syntaxin or VAMP/synaptobrevin - causes irreversible release of ACh from NMJ, which results in flaccid paralysis
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| clinical manifestations of botulism | 4-36 hrs after exposure - n/d, dry mouth, slurred speech, blurred vision, difficulty chewing and swallowing, ophthalmoplegia then descending symmetrical weakness of CNs, BUE, trunk and BLE. autonomic dysfunction
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| unique feature of botulism seen only in infants | constipation instead of diarrhea (other nl signs/sx: weak cry, lethargy, poor feeding, hypotonia, drooling and resp failure)
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| DDx for botulism | MG, Guillain-Barre syndrome, Eaton-Lambert syndrome, acute intermittent porphyria, tick paralysis, paralytic shellfish poisoning, puffer fish ingestion, organophosphates, nerve gas or atropine poisoining
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| dx of botulism | may send off a toxin assay to CDC or do cx, but you need to take charge as soon as its suspected b/c of the corresponding clinical picture
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| tx of botulism | botulinum antitoxin neutralizes circulating toxin that hasn't bound to neurons yet (not for infants). ONLY works to prevent further paralysis. // supportive tx and purgatives to expel any remaining food in stomach
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| tx of botulism for infants | baby BIG IV (botulism immune globulin)
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| abx of choice to treat wound botulism | debride and give PCN or metronidazole. DON'T GIVE clindamycin or aminoglycosides - may make things worse
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