What is the mechanism behind weakness in myasthenia gravis?

What is the mechanism behind weakness in myasthenia gravis?

• A. Destruction of dopaminergic neurons
• B. Demyelination of CNS axons
• C. Autoimmune destruction of acetylcholine production
• D. Circulating antibodies block acetylcholine receptors

Answer: (D)

Autoimmune disruption at the neuromuscular junction. In myasthenia gravis, circulating autoantibodies target the postsynaptic nicotinic acetylcholine receptors at the motor end plate. These antibodies cause receptor blockade and loss of receptors through internalization, and they activate complement to damage the postsynaptic membrane. With fewer functional receptors, the end-plate potential generated by each nerve impulse may not reach the threshold to trigger a muscle contraction. As activity continues, more receptors are occupied or destroyed, so strength diminishes with use—producing the characteristic fatigable weakness. The production of acetylcholine itself is not impaired, and this is not a central (CNS) demyelinating or dopaminergic process.

Autoimmune disruption at the neuromuscular junction. In myasthenia gravis, circulating autoantibodies target the postsynaptic nicotinic acetylcholine receptors at the motor end plate. These antibodies cause receptor blockade and loss of receptors through internalization, and they activate complement to damage the postsynaptic membrane. With fewer functional receptors, the end-plate potential generated by each nerve impulse may not reach the threshold to trigger a muscle contraction. As activity continues, more receptors are occupied or destroyed, so strength diminishes with use—producing the characteristic fatigable weakness. The production of acetylcholine itself is not impaired, and this is not a central (CNS) demyelinating or dopaminergic process.