Cholinergic receptors - myasthenia gravis Flashcards
What is myasthenia gravis?
Autoimmune attack on skeletal muscle - leads to muscle weakness and fatigue
MG is more common in women than men, like all autoimmune diseases. True or false?
True
Causes of MG are unknown, but removal of thymus gland have proven to be beneficial for women that suffer. True or false?
True
Which receptors are the target of the autoimmune attack?
Nicotinic receptors on the muscle membrane
Most antibodies in MG target the same part of the nAChR, which region and where in particular is it?
Main immunogenic region
extracellular part of the alpha subunits, specifically amino acids 67-76
On binding of antibodies to the alpha subunits on nAChRs, what are the 3 pathological processes that take place?
1- receptors are internalised -
antibody binds to receptor, the cell to which receptor belongs to recognises that something is wrong and receptor is endocytosed.
Inside cell, it is broken down into amino acids and new proteins are formed.
Lack of nAChR on cell membrane leads to muscle contraction being compromised
2- destruction and simplification of end plate
when antibodies bind to receptor immune system recognises that it needs to attack and so there is a change in the structure of the end plate - it becomes simplified and the folds are lost. There is also a reduction in nAChRs and the synapse widens
3- antibodies binding to ACh sites on nAChRs act as competitive antagonists
Destruction and simplification of end plate in MG can be seen under a microscope. True or false?
True
Where are the first muscles usually affected by MG found?
Muscles in the face - drooping eyelids, difficulty smiling
How does testing a patient’s serum help in the diagnosis of MG?
Reveals the amount of antibodies against nAChRs. However, some patients have low antibody count, especially those whose symptoms are predominantly in the eyes
What is electromyography and how is it used to diagnose MG?
procedure where the electrical activity of skeletal muscle is measured. Can be done using surface electrodes or inserting needle electrodes into muscle.
Muscle is then stimulated and the resulting APs are recorded
Patients with MG show a decline in the size of AP on repeated stimulation
Patients administered with a short acting AChE inhibitor called ________. If the drug shows improvement in their symptoms, it provides evidence for a diagnosis of MG.
Edrophonium (Tensilon)
MG does not have a cure. True or false?
True
How can MG be treated?
AChE inhibitors - pyridostigmine, neostigmine
Immunosuppressants - azathioprine
Plasma therapy
Removal of thymus gland
