In addition, the antibodies cross-link receptor molecules, increasing receptor internalization and degradation. Bound antibody also activates complement-mediated destruction of the postsynaptic region, resulting in simplification of the end plate, characterized by structural abnormalities such as sparse, shallow, and abnormally wide or absent synaptic clefts and a 70% to 90% decrease in the number of receptors per end plate in affected muscles. The number and size of the presynaptic vesicles are normal. Electrophysiologic studies show a decreased response to acetylcholine applied to the postsynaptic membrane. Acetylcholine released at the nerve ending by the nerve impulse normally binds with acetylcholine receptors. This evokes the action potential in the muscle. In myasthenia gravis, antiacetylcholine receptor antibody binds to the acetylcholine receptor and inhibits the action of acetylcholine. Bound antibody evokes immune-mediated destruction of the end plate. Treatment has reduced the mortality rate from approximately 30% to 5% in generalized myasthenia gravis. The two basic strategies for treatment that stem from knowledge of the pathogenesis are to increase the amount of acetylcholine at the neuromuscular junction and to inhibit immune-mediated destruction of acetylcholine receptors. By preventing metabolism of acetylcholine, cholinesterase inhibitors can compensate for the normal decline in released neurotransmitter during repeated stimulation. By increasing the duration of time acetylcholine remains in the synaptic cleft, acetylcholine can bind to the end-plate receptors for a longer time, which increases the magnitude of the end-plate potential and the probability of it generating an action potential. The greater the action potential force rate, the greater the force of muscle contraction. Increasing the amount of acetylcholine released by the α-motoneurons, increasing the affinity of the skeletal muscle receptors for acetylcholine, or increasing the discharge rate of α-motoneurons could cause a similar effect. However, none of these changes would affect heart rate. The cautious use of this test in patients with heart failure results from the possibility that the decreased breakdown of acetylcholine released by the vagus nerve could decrease heart rate to dangerously low levels. Decreasing extracellular Ca2+ will increase the excitability of skeletal muscle fibers but does not have a direct effect on contractile force.
146. The answer is c. (Longo, pp 3225, 3504-3506.) Periodic hyperkalemic paralysis is a disorder of muscle membrane excitability resulting from a sodium channel disorder. Inactivation of the sodium channels on the skeletal muscle membrane prevents action potentials from being produced, and therefore leads to muscle weakness or paralysis. Although the exact mechanism of periodic hyperkalemic paralysis is not known, it appears to be due to a mutation in the gene coding for the sodium inactivation gate.
147. The answer is d. (Barrett, pp 106-107.) Phosphorylcreatine is rapidly converted to ATP in muscle. When the metabolic demands exceed the rate at which ATP can be generated by aerobic metabolism or glycolysis, phosphocreatine can supply the necessary ATP for a brief period of time. An increase in the concentration of phosphorylcreatine in muscle may increase the amount of ATP that can be produced and therefore enhance performance.
148. The answer is d. (Barrett, pp 379-380. Le, pp 94, 294, 387, 575. Longo, pp 602, 3092-3095.) Vitamin D deficiency causes defective calcification of the bone matrix as a result of inadequate delivery of Ca2+ and PO43−