5

5 CASE 5

A 65-year-old man comes to his primary care physician complaining of a decreasing ability to read that is more pronounced in the evening. The difficulty is due to a combination of diplopia and blurred vision.

The patient has a 15-year history of hypertension that is being managed with diuretics and a low salt diet. He began using bifocals for reading about 10 years ago, and his current eyeglass prescription allows him to see comfortably.

PHYSICAL EXAMINATION

VS: T 37°C, P 75/min, R 15/min, BP 130/90 mm Hg, BMI 28

PE: Neurologic examination indicated normal sensory responses. Deep tendon reflexes were normal, although a small amount of muscle weakness was present.

DIAGNOSIS

Myasthenia gravis

COURSE

Myasthenia gravis is an autoimmune disease in which antibodies attack the acetylcholine receptors on the motor end plate region of the muscle cell. The symptoms are due to both the inactivation of the acetylcholine receptors and to the disruption of the histology of the motor end plate region.

PATHOPHYSIOLOGY OF KEY SYMPTOMS

Neuromuscular transmission requires the release of an appropriate amount of acetylcholine into the synaptic cleft, the diffusion of the acetylcholine across the cleft, and the binding of the acetylcholine to the receptors on the motor end plate region of the skeletal muscle cell. Binding of acetylcholine to the receptors opens a cation channel that is equally selective for Na⁺ and K⁺, and there is a subsequent depolarization of the end plate region to −15 mV. The depolarization generates an action potential that spreads along the skeletal muscle cell, causing Ca⁺⁺ release from the sarcoplasmic reticulum and inducing a contraction.

Myasthenia gravis is a chronic autoimmune disease leading to destruction of the acetylcholine receptors on the motor end plate region of muscle cells. Acetylcholine release from the α-motor neuron synapse, however, remains normal.

Normally, the amount of acetylcholine released by an α-motor neuron action potential is in excess of the amount needed to generate a skeletal muscle action potential. The threshold for an action potential in skeletal muscle is about −40 mV, so there is a large safety factor in neuromuscular transmission. Consequently, a noticeable impairment of neuromuscular transmission does not occur until approximately 70% of the acetylcholine receptors have been damaged.

Although acetylcholine release is normal, the absence of functional receptors on the motor end plate region of the muscle cell means that the biologic response is diminished. Normally, acetylcholine is degraded in the synaptic cleft by the activity of the enzyme acetylcholinesterase. Drugs such as edrophonium inhibit acetylcholinesterase. Therefore, an improvement in function after edrophonium confirms a defect in acetylcholine/receptor interaction.

Sequential nerve stimulation results in a reduced amount of acetylcholine released from the nerve terminal. This is not normally evident because of the large safety factor for neuromuscular transmission. However, when the number of receptors on the muscle cell is diminished there is a reduction in the strength of contraction that is detected by the repetitive nerve stimulation test.

The diagnosis of myasthenia gravis is based on the presence of antibodies against the acetylcholine receptor. The disruption of the motor end plate region of the skeletal muscle cell can also be detected histologically from a biopsy.

Myasthenia gravis is often associated with a tumor of the thymus gland. For these patients, thymectomy can provide significant relief or complete remission of symptoms.

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Tags: Problem-Based Physiology

Jul 4, 2016 | Posted by admin in PHYSIOLOGY | Comments Off

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