Question

After the high school group finishes their tour, Dr. Wayne sees two patients. Jeff Slater is a biochemist working for a biowarefare lab at the CDC. He is currently working on a project to develop a new neurotoxin and is using sarin as a model substance. Suddenly while working the lab alarms go off and Jeff accidentally knocks a vial of sarin over and a bit of the liquid splashes onto his arm between his gloves and lab coat. He suddenly starts to feel dizzy, his heart starts pounding harder than ever, and he has shortness of breath. He feels incredibly sluggish and tries to get to the exit. As he approaches the lab door, his muscles cramp up and he falls down and hits his head, knocking him unconscious. His colleague from across the hall happens to see him fall and calls for help. Jeff is given oxygen and taken to the nearby hospital, which happens to have a neuromuscular specialist. The sounding of the alarm turns out to have been just routine testing of a new system.

1. Dr. Wayne looks over the results and finds that the acetylcholinesterase activity is lower than normal. The normal range is 100% and Jeff's range is 44%. Dr. Wayne knows from Jeff ’s colleague that he is a bioweapons biochemist. Dr. Wayne figures out that Jeff has been working on synthesizing a new sarin-like biochemical weapon and suspects Jeff has a type of poisoning that is similar to that of sarin. What is the mechanism of action of sarin or a sarin-like chemical? How would exposure to a sarin-like poison affect the amount of sodium going into the muscle cell? What needs to happen to Jeff's post-synaptic membrane to remedy his paralysis. Physiologically what do we need more of and where?

Answer 1

In a normal cell, Acetylcholinesterase found in the synapse between nerve cells and muscle cells. breaks down the acetylcholine into its two component parts, acetic acid and choline. This effectively stops the signal, allowing the pieces to be recycled and rebuilt into new neurotransmitters for the next message, so this low concentration of acetylcholine at the synapse must be maintained for another impulse to occur.

Sarin is a potent organophosphorus nerve agent that inhibits acetylcholinesterase (AChE) irreversibl, this results in the accumulation of acetylcholine in the synapse,this inhibition of acetylcholinesterase, means the neurotransmitter continues to act on the muscle fibre, so that any nerve impulses are effectively continually transmitted, this results in symptoms of sweating, bronchial constriction, convulsions, paralysis, and possibly death can occur at higher doses.

If acetylcholinesterase activity is inhibited, the synaptic concentration of acetylcholine will remain higher than normal.this means acetylcholine receptors at the post synaptic cell are not activated, this will cause depolarization not to occur, that means sodium ions cannot move into the cell. ( for a depolarization to occur sodium ion must move into the cell and potassium ion moves out of the cell)

Atropine, an antagonist to acetylcholine receptors, is given to treat the physiological symptoms of poisoning as in this case. Some drugs like pralidoxime can be given, which acts by regenerating cholinesterase, assuming if given in first few hours after exposure to the nerve gas.