Reference no: EM133457186
Assignment:
Explain how the frequency of delivery of the vesicles and Ach on the "normal motor neuron and muscle association" section (3rd paragraph) can influence the depolarization at the motor end plate of the skeletal muscle and how it affects muscle contraction?
Nervous System Case Study
A 54-year-old woman returns to her oncologist for continuing treatment of recurring ovarian cancer. It has been 2 days since the last treatment, and she is now complaining of paresthesia of the hands and feet and difficulty in fastening buttons due to muscle weakness in the hands.
The woman began treatment for the ovarian cancer 2 months ago. The treatment regimen includes paclitaxel (Taxol), 150 mg/m2; gemcitabine, 800 mg/m2; and cisplatin, 75 mg/m2, three times a week for 6 cycles. She was diagnosed with diabetes mellitus type 2 at age 35 and has successfully manage it with insulin glargine, 0.2 units/kg; glipizide, 1-5 mg tablet twice a day; and metformin, 1-500 mg tablet twice a day . The patient has lost body hair due to the chemotherapy, her appetite remains good, and nausea is being managed.
Physical Examination (PE) and Vital Signs (VS)
VS: T 37 oC; P 75/min; R 18/min; BP 128/84 mm Hg; BMI 34
PE: sensory neuropathy (tingling) present in the hands. Deep tendon reflexes were diminished bilaterally.
Laboratory Studies
NONE
Diagnosis
Taxol-induced peripheral neuropathy
Course of action
The sensory and motor neuropathies resolved over the next 5 days.
Pathophysiology of key symptoms
During the last visit with her doctor, the patient was informed that 2 of the medications that were prescribed, Cisplatin and Paclitaxel (Taxol), disrupt the microtubule function by polymerizing the tubules, and block cell mitosis. The effect of the medication in general is that the cells that are in the process of dividing are targeted and killed.
Case study continues.
The doctor further explained to the patient that the reason she was having problems with fastening the buttons and muscle weakness was because of the disruption of the microtubules. The doctor further explained that the issue is associated with a neuromuscular junction.
Normal motor neuron and muscle association.
Normal neuromuscular transmission requires the release of Acetylcholine (ACh) from the synaptic vesicles in the motor neuron of the presynaptic terminal (axon terminal). Diffusion across the synaptic cleft, and binding to the receptors at the motor end plate region of the skeletal muscle cell.
The ACh is degraded by the enzyme acetylcholinesterase into acetate and choline. The choline is transported back into the pre-synaptic terminal and returned to the recycled portion of the vesicle. Ach is resynthesized, and the vesicle is ready for reuse.
Skeletal muscle electrical activity consists of miniature end plate potentials. The miniature end plate potentials result from the release of the Ach, usually a 0.4 mV depolarization in the muscle cell. The magnitude of the miniature end plate potentials will not be altered normally because each vesicle contains a normal amount of ACh, but their frequency can be diminished. A normal motor neuron action potential causes the release of about 125 vesicles. That quantity of ACh released into the synaptic cleft causes a -40 mV depolarization at the motor end plate, which is sufficient to elicit an action potential, and cause a contraction of the skeletal muscle (more on this on the muscle physiology lecture). Because of effect on Paclitaxel, the difference in the quantity of ACh released by a motor neuron does not result in a skeletal muscle contraction, muscle weakness develops, which is what the patient is experiencing.
One side effect of Paclitaxel is also damage to Schwann cells, leading to diminished nerve conduction velocity in both motor and sensory neurons, thus nerves as well, particularly large, myelinated nerves.
One other aspect of the treatment that is important to understand is that muscles that are distal have the longest distance for vesicle transport, and consequently, are more sensitive to microtubule disruption.