Print

Myasthenia gravis

(from the Greek and Latin = severe muscle weakness) is a disease in which result in weakness and fatigue of striated muscles.

How does neuromuscular transmission?

Muscles are normally activated after receiving the signal, nerve impulse, from the central nervous system (see figure at the end of this page). At the ending of the peripheral nerve there are vesicles with acetylcholine (ACh), that acts as a chemical messenger. Vesicles are accumulated near the membrane nerve terminal. After arriving in the nervous excitement of the nervous endings, is released ACh quantum (the contents of vesicles) in the so-called neuromuscular crevices occupy binding sites on acetylcholine receptor (AChR), which towers on the surface of muscle cells. In these places the muscle cell membrane called distorted junkčními folds. Receptor consists of 5 subunits (2 alpha, the beta and delta epsilon) for ACh binding site is located on the alpha subunit. Then the penetration of sodium and potassium through receptor and muscle fiber can be downloaded. In order to operate normally neuromuscular transmission, ACh must be inactivated, then split into 2 components ineffective (acetyl and choline). This is an enzyme, acetylcholinesterase. This whole complex consists of neuromuscular plate.



information about neuromuscular transmission

animation  quiz

neuromuscular junction




 

 

The video shows the mechanisms associated with the transition of the nervous impulse to muscle



Disorders of immunity in myasthenia gravis

In myasthenia is a neuromuscular disorder that leads to formation of antibodies against acetylcholine receptor, which block its function, and even with the so-called complement receptor destroyed. It was recently discovered another type of antibody against the acetylcholine receptor that enables the "nestle" in the postsynaptic membrane (for a muscle-specific receptor tyrosine kinase - MuSK). Antibodies are created so-calle
d plasma cells that arise from white blood cells - B lymphocytes. B lymphocytes are "rogue" that are constantly flogging the activity, such as substance BAFF (activating factor for B cells), or APRIL (proliferating factor). These cells also receive bad information from another type of cells called T lymphocytes. It is particularly impaired function of regulatory T cells to maintain a balance between  various ells and their products. All these cells communicate via chemicals - cytokines and chemokines, receive information on their surface, which protrude special receptors.



Myasthenia is a typical autoimmune disease  

1/ The disease can be modeled on an experimental animal. Applications purificated AChR with the animal muscle weakness occurs. This model is called autoimmune experimental myasthenia gravis (EAMG).

2 / EAMG serum can be transferred to another animal, which will  also become ill.

3 /
Creation of antibodies against AChR is typical for myasthenia


4 / plasma exchange  and removal of the thymus in younger patients, in humans the symptoms temporarily improved.

Myasthenia is the first disease for which the proof that it is an auto-immune diseases.


Autoimmunity: link to Wikipedia

 


 

What are the necessary conditions for the myasthenia was?

1/ Genetic (congenital disposition). Myasthenia is not a typical hereditary disease, it is a polygenic disease, meaning that it must be exceptional circumstances - failure (mutation) of several tens of different genes.

2 / Malfunction of the immune system (over-stimulation of B cells, impaired function of regulatory T lymphocytes and many other abormit).

3 / The immune system is very sensitive and prone to damage from external environmental influences.

4 / Malfunction of the immune system can cause various infectious factors (the so-called suspected herpes viruses, chlamydia and others).



Everything you can imagine is like a puzzle, where everything must fit together so that we could see the final image - in our case the disease.


 

On the electron microscope images can be seen that the normal state in the nerve endings of axon (AX) and acetylcholine vesicles with the postsynaptic junction is distorted (SC), while in myasthenia is balanced and destroyed along with the disappearance of receptors.

 


Important role played by the thymus of myasthenia (thymus). It is located in the mediastinum between the lung lobes of the breastbone. Younger pacents (up to approximately 50 years) with myasthenia occurs in the inflammation. This is due to the fact that the thymus has muscles like cells (myoid cells), whose components (antigenic epitopes) are recognized as a foreign to the body. Bearings inflammation (germinal center) are visible as an accumulation of white blood cells called autoreactive B and T lymphocytes, which are entering the blood circulation and stimulate the destruction of the receptors. In elderly patients with impaired immune function of the whole organism. 


Histology of thymus

normal thymus thymus in myasthenia gravis


Myasthenia is sometimes found together in other autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, psoriasis, autoimmune thyroid disease, type 1 diabetes, inflammatory muscle diseases, multiple sclerosis, etc.), that were slowly but surely increasing. Some of them can be found in the section links. Currently (2009) estimated the number patients in CR tis o about 2 400 and the number of newly diagnosed patients per year to 220 More often ill younger women and older men (probably as the influence of sex hormones).

 

Clinical syptoms - symptoms of disease

The main symptoms include fluctuating muscle weakness and fatigue, which occurs, or worse after the exertion. Typically, highlighting difficulties in the afternoon and evening hours (exceptionally well in the morning after waking up). Symptoms may worsen after infection, increased body temperature, mental stress, improper administration of drugs, etc. The most commonly affected extraocular muscles (eyelids falling and / or double vision - it is the most common first symptoms of the disease). In about 20% of cases occur so-called ocular myasthenia, during disease, no other affected muscles - generalization. They may also be affected facial muscles. May be apparent mimicry of failure - is "hard" facial expression, smile, imperfect, or the "half-mouth". Weaknes eyelids causes such as postnasal shampoo in the eye. Biting the food diminishes, especially for stiffer food, food processing still remains between the gums and mucous membranes allowed, so it is sometimes necessary to help yourself fingers. Swallowing is slow, the fluid may even leak into the nose, it is difficult even tougher swallowing food, for example chewed up bread sticks to the palate, minor bites stay in the nasopharynx (rice and suchlike)The specech during articulation the speech becomes unclear, lisping, mumbling and at the end it almost non-understandable.
At a weakening of neck muscles gradual drop, even falling of the head occurs. Weakness of girdle muscles shows as fatigue and gradually growing weakness at an activity arms upwards (hanging out the washing, shaving, brushing teeth and suchlike.), falls and difficult climbing the stairs. Myasthenic crisis is urgent and very malicious condition which becomes apparent weakening of breathing muscles, beginning with the crisis is reflected in dyspnoea, worse for a reclining load, significant anxiety and unrest, and eventually stop breathing.

Education program .




In the picture is apparent path of nervous excitement - from the nerve cells to neuromuscular junction