Myasthenia Gravis - Anatomy & Physiology

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  • Dr. Swathi can i have a request, i want your help and study your notes for my MedSurge subjct, i find your notes better that our clinical instructors teachings. yours is more accurate and much better to read. thanks , just email me in my acount loybiloy@gmail.com and add me in facebook, buloyagonz agetro, thanks :D
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Myasthenia Gravis - Anatomy & Physiology

  1. 1. By: Dr. Swathi Prof Dr A.Gowrishankar’s unit
  2. 2. <ul><li>Each muscle fibre is connected to a nerve fibre branch coming from a motor neuron </li></ul><ul><li>Stimulation from motor neurons initiates the contraction process. </li></ul><ul><li>The motor neuron and all the muscle fibres it innervates are called a motor unit . </li></ul><ul><li>The site at which motor neuron attaches on the muscle cell is known as the neuromuscular junction </li></ul>
  3. 3. <ul><li>Details of these junctions vary in different skeletal muscle fibres as follows: </li></ul><ul><li>1) Motor end plates </li></ul><ul><li>2) En grappe endings </li></ul><ul><li>intrafusal fibres </li></ul><ul><li>3) Trail endings </li></ul>
  4. 5. <ul><li>Sole plate( it’s a specialized area of the muscle </li></ul><ul><li>fibre) + axon terminal motor end plate </li></ul><ul><li>MOTOR END PLATE COMPRISES OF: </li></ul><ul><li>Pre synaptic membrane(axolemma) </li></ul><ul><li>Synaptic cleft primary cleft (40nm) </li></ul><ul><li>secondary(subneural) </li></ul><ul><li>cleft </li></ul><ul><li>Post synaptic membrane </li></ul>S A R C O L E M M A
  5. 6. <ul><li>Axon terminals contain synaptic vesicles & are rich in mitochondria </li></ul><ul><li>Pre synaptic terminal contains voltage gated Ca 2+ channels </li></ul><ul><li>In the region of the sole plate sarcoplasm is rich in mitochondria, ER & golgi complexes </li></ul><ul><li>Post synaptic membrane contains Ach receptors & voltage gated Na 2+ channels </li></ul>
  6. 9. <ul><li>An AP propagates down the axon </li></ul><ul><li>invades and depolarizes the presynaptic </li></ul><ul><li>terminal region </li></ul><ul><li>Ca2+ flows into the boutons through voltage-activated Ca2+ channels </li></ul><ul><li>Fusion of synaptic vesicles with pre-synaptic membrane & the release of &quot;packets&quot; or quanta of transmitter into the cleft. </li></ul>
  7. 11. <ul><li>In the case of the neuromuscular junction, the transmitter released is acetylcholine(ACh). </li></ul><ul><li>It is important to note that the amount of transmitter released is directly related to the amount of Ca2+ that enters the bouton, which is directly related to the number, amplitude and duration of the invading action potentials. </li></ul>
  8. 12. <ul><li>The Ca2+ channels involved are not located along the axon, only at the terminal ‘boutons’. </li></ul><ul><li>The vesicles fuse to the terminal membrane via specialized docking proteins. </li></ul><ul><li>Vesicle membrane is recycled, but that system can be overwhelmed </li></ul>
  9. 13. <ul><li>ACh diffuses across the cleft. This takes time (up to several hundred microsec). </li></ul><ul><li>ACh binds to Nicotinic ACh receptors in the post-synaptic membrane, opening monovalent cation channels </li></ul><ul><li>Channel opening depolarizes the post-synaptic membrane, creating an endplate potential (EPP). </li></ul><ul><li>If EPPs exceeds a threshold value </li></ul>
  10. 14. <ul><li>Voltage-activated Na+ channels open giving rise to a muscle AP. </li></ul><ul><li>Termination of the transmission process occurs via hydrolysis of ACh by acetylcholinesterase present in the junction. </li></ul>
  11. 17. <ul><li>Three possible immunological mechanisms— </li></ul><ul><li>1)Actual degradation the receptor site by complement activation by IgG </li></ul><ul><li>2)Accelerating the degradation of anticholinesterase receptor through the cross-linking phenomenon. </li></ul><ul><li>3)Directly blocking the receptor site. </li></ul>
  12. 18. <ul><li>The no of AChRs at the neuromuscular junction are reduced to approx 20% of normal levels </li></ul><ul><li>EPP is reduced in amplitude & fails to reach the threshold </li></ul><ul><li>EPP becomes smaller during repeated efforts </li></ul>
  13. 21. T H A N K U

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