43. diseases of neuromuscular junction. toxicosis, tetanus, botulism Flashcards
NMJ disorders fifferentiation
presynaptic: decreased release of acetylcholine
postsynaptic: Ach receptor related
enymatic: Ach esterase inhibitors
list presynaptic diseases
LMN type deficits (hypotonia, hyporeflexia)
botulism
list postsynaptic diseases
exercise induced weakness
myasthenia gravis
list toxic diseases
tetanus strychinine poisoning ivermectin poisoning lead toxicosis methaldehyde toxicosis pyrethrins ethylene glycol
what is presynaptic disease?
inability to release Ach from presynaptic channels
botulism
tick paralysis
botulism etiology
neurotoxin from C. botulinum
ingestion of preformed neurotoxin
botulinum toxin irreversibly cleaves a protein that docks Ach vesicles at presynaptic membrane
botulism clinical signs
acute paresis starting in hindlimbs
facial nerves can be involved - facial paralysis, dysphonia
autonomic signs: ileus, tachycardia, urinary retention, Megaoesophagus
botulism diagnosis
history, clinical signs, toxin analysis
botulism treatment
supportive: fluid, bladder expression, feeding tube
AB NOT indicated - toxin not bacteria
antitoxin - don’t work for toxin already in nerves, only circulating toxins
prognosis good, recovery after 2-4 weeks
postsynaptic disease
inability of postsynaptic membrane to react to Ach
congenital myasthenia gravis
aquired myasthenia gravis
organophosphate, carbamate toxicosis
myasthenia gravis acquired vs congenital
congenital: deficiency or abnormality of Ach receptors
aquired: antibodies produced against Ach receptors -> low number of functioning receptors
three forms of myasthenia gravis
fulminant
focal
generalized
generalized myasthenia gravis
normal at rest
exercise induced - get more and more tired, rest and get better
unknown background
can have concurrent autoimmune or endocrine disorder: hypo, hyperthyroidism
focal myasthenia gravis
weakness of one muscle group
laryngeal paralysis
megaesophagus
fulminant myasthenia gravis
no improvement at rest
generalized weakness
myasthenia gravis diagnosis
tensilon test (anticholinesterase)-> weakness disapear for a moment determination of Ach receptor antibodies
myasthenia gravis treatment
Ach esterase inhibitor: pyridostigmine bromide
sometimes immunosuppression
exercise induced collapse of lab retrievers
similar to myasthenia gravis
exercise - overheat- fatigue, flaccid paralysis
genetic disorder
genetic test available
organophosphate, carbamate toxication
insecticides, flea collars
inactivate Ach esterase - increased Ach - increased stimulation (tonic-clonic seizure, facial twitch)
vegetative overstimulation (muscarinic Ach receptors -> salivation, lacrimation
pralidoxime: resolution of nicotinic effect of Ach on skeletal muscle
Atropine: resolution of muscarinic signs
tetanus etiology
cl. retain into anaerobic wound - neurotoxin production
toxin (tetanospasmin) enter blood stream, - > neuron->inhibitory interneurons => inhibit glycine and GABA release
LOSS of inhibition of motor neurons -> rigid paralysis
tetanus - forms, incubation
local tetanus
general tetanus
incubation 1-2 weeks
progression until day 4-7
tetanus signs
extensor rigidity - saw horse
ricis sardinosus - special grin expression (facial muscle spasm)
difficulty swallowing - salivation
stimuli further increase symptoms
tetanus treatment
debridement of wound if found
AB: penicillin, metronidazole, tetracycline
antitoxin - can cause allergic reaction
muscle relaxants - acepromazine, diazepam
supportive care: feeding tube, empty bladder, turning
quiet environment
strychinine poisoning
alkaloid from strychnine tree
glycin antagonist (glycin is inhibitory signal)
(in small dose it increase salivation and appetite-appetite stimulant)
rigid paralysis - saw horse
retraction of mouth, ears pulled back
hypersensitive to stimulation
ivermectin poisoning
anti parasitic drug, MDR1 gene mutation dogs sensitive
GABA antagonist, bind to gaba receptor
salivation, vomiting ataxia, tremors
supportive treatment
lead toxicosis etiology, clinical signs
ingesting lead
lead inhibit sulfhydryl groups of important metabolic enzymes
Gi signs, hematology change(microcytic, hypo chromic anemia)
lethargy, ataxia, seizure, blindness, anorexia
lead toxicosis diagnosis, treatment
determination of lead levels in blood, urine, liver, kidney
1: remove lead source
2: calcium EDTA IV
3: sedative, anticonvulsant
4: diuretics
5: short acting GCC
methaldehyde toxicosis
slug drug ;) decomposed to acetaldehyde in stomach
acetaldehyde and methaldehyde rapidly absorbed-> Elin signs appear fast
decrease conc of GABA, and serotonin
panting, salivation, trembling, seizures
methaldehyde toxicosis therapy
no specific therapy
diazepam, methocarbamol for seizures, trembling
pyrethrin toxicosis
aldehyde of chrysanthemum plant
used as insecticide
inhibit Ca/Mg-ATP-ase in nervous tissue (atpase helps muscle relaxation)
pyrethrin toxicosis - who is sensitive
cats are sensitive low hepatic glucuronidase activity, slow metabolism -> toxicosis seizure, tremor supportive therapy good prognosis
ethylene glycol toxicosis mechanism, clinical signs
ethylene glycol degraded to toxic metabolites
- glycolaldehide, glyoxylic acid, oxalic acid, glycolic acid
1. apathy, salivation, ataxia (like drunk)
2. AKI
ethylene glycol toxicosis, diagnosis treatment
US: halo sign on kidney due to oxalate crystals
urine: ca oxalate crystals
IV ethyl alcohol
