Organophosphate Poisoning

00:01 In this lecture, we're going to talk about other types of neuromuscular Junction disorders.

00:06 We've talked about myasthenia gravis, botulism and Lambert-Eaton myasthenic syndrome in other lectures and those are the three most commonly encountered or tested conditions.

00:17 This will be a group of disorders that it is important to know of but not know all the details about What are the categories of other neuromuscular junction conditions? Well toxic and metabolic nutritional disorders can affect the neuromuscular junction and the condition we're going to learn about is organophosphate poisoning.

00:37 There are also inherited and congenital conditions that affect the neuromuscular junction and we're going to talk briefly about neonatal myasthenia and congenital myasthenia.

00:48 Let's start first with organophosphate poisoning.

00:51 Organophosphate are irreversible acetylcholinesterase Inhibitors.

00:56 Remember that that acetylcholinesterase enzyme lives in the synaptic cleft breaks down acetylcholine and recycles the neuromuscula junction to allow a new transmission to occur.

01:08 Organophosphate poisoning results from irreversible depolarization of the neuromuscular junction.

01:14 As a result of inhibit inhibition of this acetylcholinesterase enzyme, there is continuous depolarization of the neuromuscular Junction.

01:24 What's the path of physiology? Well initial depolarization of the neuromuscular junction results in muscle activation, but long term depolarization, desensitizes the muscle and patients present with weakness.

01:39 Muscles are no longer able to activate or respond appropriately to continued acetylcholine release.

01:47 This condition also affects other postganglionic parasympathetic and some sympathetic fibers.

01:54 And so the mnemonic that we think about for the associated symptoms that present with organophosphate poisoning is sludge.

02:02 And I like this mnemonic because it reminds us of things to think about in patients who may have ingested organophosphates.

02:07 We think about salivation, lacrimation, urination, diarrhea, GI dysmotility and emesis and those are things that we should evaluate and look for and hear about and should tip us off to considering organophosphate poisoning.

02:24 In a patient who presents with possible ingestion.

02:26 We also need to think about the potential cardiac complications patients can develop bradycardia and hypotension as well as hemodynamic compromise as a result of increased parasympathetic tone on the heart.

02:39 All of these symptoms result from increased parasympathetic tone and increased activation of those postganglionic parasympathetic fibers.

02:50 So what's going on with organophosphate poisoning? Well, normally acetylcholine signaling at the synapse occurs as you see on the far left.

02:59 The pre synaptic vesicles bind to the synaptic membrane acetylcholine is released.

03:03 It activates the acetylcholine receptor and we get muscle contraction.

03:08 Acetylcholinesterase stops this signaling and so normally the acetylcholinesterase enzyme lives in the synaptic cleft.

03:15 It binds up the acetylcholine breaks it down and recycles the neuromuscular Junction.

03:22 In the settings of organophosphate poisoning, there is irreversible inhibition of the acetylcholinesterase enzymes.

03:30 And so we see continuous activation of those junctions.

03:33 We see more acetylcholine in the synaptic cleft, more firing at the postsynaptic membrane and this drives patient symptoms.

03:41 This leads to the sludge.

03:43 As a result of activation the postsynaptic, postganglionic fibers, we see salivation lacrimation and urination and diarrhea and defecation, GI dysmotility, as well as convulsions and he's an even tremors.

03:54 And at the level of the muscle continuous depolarization of the muscle membrane down regulates and results in muscle de-sensitivity.