A 46-year-old man comes to the emergency department due to worsening blurry vision, difficulty swallowing, and dry mouth for the past hour. He has also been having nausea and abdominal discomfort but has no headache or fever. The patient has no prior medical conditions and takes no medications. He smokes a pack of cigarettes daily but does not use alcohol or illicit drugs. The patient has not traveled recently but attended a community potluck event yesterday where he sampled home-canned foods. Physical examination shows bilateral ptosis and sluggish pupillary response. Which of the following steps in neuromuscular transmission is most likely affected in this patient?

Question

A 46-year-old man comes to the emergency department due to worsening blurry vision, difficulty swallowing, and dry mouth for the past hour.  He has also been having nausea and abdominal discomfort but has no headache or fever.  The patient has no prior medical conditions and takes no medications.  He smokes a pack of cigarettes daily but does not use alcohol or illicit drugs.  The patient has not traveled recently but attended a community potluck event yesterday where he sampled home-canned foods.  Physical examination shows bilateral ptosis and sluggish pupillary response.  Which of the following steps in neuromuscular transmission is most likely affected in this patient?

Quizplus · Accepted Answer

11ec160b_387b_ee8a_9249_41ca05d3185a_MD0001_00 This patient with gastrointestinal discomfort has manifestations of both nicotinic blockade (eg, dysphagia, ptosis) and muscarinic blockade (eg, dry mouth) that developed after eating home-canned food. This is strongly suggestive of food poisoning with Clostridium botulinum toxin, a preformed neurotoxin. Botulism characteristically presents as a symmetric, descending paralysis that first manifests with cranial nerve abnormalities (diplopia, dysphagia, dysphonia ["3Ds"]). Nausea, vomiting, and abdominal pain may also occur in foodborne botulism, which classically occurs 12-36 hours after consumption of contaminated, home-canned foods. Botulinum toxin causes disease by inhibiting cholinergic nerves, including nicotinic and muscarinic motor neurons. It enters the nerve terminals through endocytosis, where it prevents binding and fusion of acetylcholine (ACh)-containing synaptic vesicles with the plasma membrane through the destruction of SNARE proteins. This effectively blocks ACh release into the neuromuscular synapse. Botulinum toxin is highly potent; a very small quantity can be lethal without ventilatory support. The toxin is heat-labile, so disease can be prevented by thoroughly heating food prior to consumption. (Choice A) Hemicholinium blocks choline uptake by the presynaptic neuron, preventing ACh synthesis through depletion of intracellular choline. (Choice B) Bromoacetylcholine inhibits choline acetyltransferase, blocking the synthesis of ACh from acetate and choline. (Choice C) Vesamicol noncompetitively blocks the vesicular ACh transporter, preventing ACh from entering secretory vesicles in the presynaptic nerve terminal. (Choice E) Acetylcholinesterase inhibitors such as organophosphates (commonly used as insecticides) prevent ACh breakdown. Manifestations of organophosphate poisoning reflect depolarizing blockade (eg, muscle weakness, fasciculations, paralysis), central nervous system effects (eg, lethargy, seizures), and muscarinic overstimulation (eg, miosis, bradycardia, increased lacrimation and salivation). (Choice F) Anticholinergic poisoning due to competitive antagonists of muscarinic ACh receptors (eg, atropine, scopolamine) is relatively common and can manifest as cutaneous vasodilation, anhidrosis, hyperthermia, mydriasis, and delirium. However, these agents have no effect on the nicotinic ACh receptors controlling voluntary muscles. Poisoning due to nicotinic receptor antagonists (eg, pancuronium, tubocurarine) is uncommon as these agents have poor oral absorption. Educational objective: Botulinum toxin blocks the presynaptic exocytosis of ACh vesicles, causing impaired muscarinic and nicotinic neurotransmission; it characteristically presents as a symmetric, descending paralysis that first manifests with cranial nerve abnormalities, often following consumption of home-canned foods. __________ References: Large outbreak of botulism associated with a church potluck meal-Ohio, 2015. (http://www.ncbi.nlm.nih.gov/pubmed/26225479)

A 46-Year-Old Man Comes to the Emergency Department Due to Worsening