Case Study: Muscle
Problem Introduction: 1 of 3 Muscle Weakness/ Myasthenia Gravis
The motor pathway consists of a large number of elements organized in a functional sequence. A motor action involves these elements, one after the other, to bring about the shortening and force generation by skeletal muscle. Malfunction of any one of these elements can affect muscle strength and coordination.
A patient came to his physician complaining of muscle weakness.
- List the loci along the complete motor pathway where some defect could result in muscle weakness.
- Upon testing the patient, the following observations were made:
- Repetitive voluntary activity was associated with normal action potential activity in the motor nerve, although the patient’s muscles rapidy fatigue and muscle force declined.
- Repetitive direct electrical stimulation of muscle resulted in normally sustained force without evidence of fatigue.
Assuming that a single site of pathology is present, where along the motor pathway is the patient’s problem? Explain your reasoning. Create a concept map begining with Myasthenia gravis and terminating with muscle weakness and fatigue.
- What might be done to help such patients?
Problem Introduction: 2 of 3 Excitation/Contraction Coupling
Neural activation of skeletal muscle involves a sequence of steps. Understanding the steps in this sequence helps to determine the locus of disturbances that affect muscle activation.
You are given an isolated muscle with its motor nerve intact. This preparation is arranged so that you can make electrophysiological measurements from the nerve and the musle as well as mechanical measurements of the muscle contraction. You observe that caffeine is added to the fluid bathing the preparation, the peak tension developed in the muscle twitch produced by stimulating the motor nerve is increased.
- List the possible loci at which caffeine may be exerting its effect.
- Caffeine is known to alter transmembrane movement of Ca2+ . What is (are) the possible site(s) at which caffeine is acting?
- High concentration of caffeine causes an isolated muscle to contract in the abscence of any activity in the motor nerve. This contraction is not blocked by nicotine blocking agents like curare. Where do you think caffeine acts?
Problem Introduction: 3 of 3 Malignant Hyperthermia
Activation of skeletal muscle occurs through a complex sequence of events, leading to contraction (shortening) or force generation. Abnormal responses at any of these steps will alter muscle function and possibly whole body homeostasis.
An essential step leading from excitation of skeletal muscle to contraction is the liberation of stored biochemical energy (from the high-energy phosphate of ATP) by the myosis ATPase (located on the crossbridge). It then follows that the muscle must have a store of ATP and the ability to generate new, replacement ATP (whether by the normal process of oxidative phosphorylation or by anaerobic pathways).
Most of the energyliberated from ATP, hoowever, appears as heat and is not converted into mechanical energy. Skeletal muscle therefore plays an important role in temperature homeostasis. For example, muscle is used to increase heat production by shivering when body temperature must be maintained in a cold environment. On the other hand, in a 70 kg individual, skeletal muscle accounts for approximately 30 kg of body weight, and the heat generated by active skeletal muscle represents a major part of the heat load that must be dissapated by the body.
Malignant hyperthermia is a relatively rare response to certain forms of anethesia. It is caused by an unknown mechanism that gives rise to an increase release in Ca 2+ release from the sarcoplasmic reticulum, producing skeletal muscle contractures ( continuous, sustained contractiuons resulting in muscle rigidity) accompanied by hypermetabolic state: muscle tissue oxygen use is increased and thus carbon dioxide production is increased; there is acidosis and hyperpnea (from elevated carbon dioxide). Most importantly, there is a very rapid rise in heat production and body temperature, which can be life threatening.
This condition appears to involve an inheritable fdefect in muscle metabolism that may be activated by halothane anesthesia; Ca2+ stored in the sarcoplasmic reticulum is released into the muscle cytoplasm where it causes sustained muscle contraction. This reaction does not necessarily occur on the first exposure to this anesthetic agent, and its occurance is not easily predicted.
Treatment for this response calls for immediate cessation of anesthesia, cooling the body with ice packs, and the use of dantrolene, a drug that specifically reduces the release of Ca 2+ from the SR.
Muscle is a biochemical machine that converts chemical bond energy into mechanical force or shortening.
Diagram the sequence of steps from the motor nerve to the contraction of the skeletal muscle cell that occurs.
- Biochemical processes give rise to a waste products that in many cases pose a homeostatic challenge for the organism. What are the inevitable by-products of muscle contraction with which the body must coap?
A 25-year-old man was brought to the emergency room with a broken leg. His medical history was unremarkable, although he reveals that his mother had died of some �complication� following a hysterectomy.
The patient was taken to surgery for repair of his fractured left distal tibia. He was premedicated with, among other drugs, succinylcholine (a muscle relaxant) and was placed on a ventilator. It was noted that vigorous muscle fasciculation began almost immediately. Nevertheless, general anesthesia was begun with halothane.
- Succinylcholine binds to Ach receptors at the motor end plate. Explain the mechanism by which it could produce muscle relaxation.
- Explain the mechanism by which fasciculation could occur following administration of succinylcholine.
There was an immediate tachycardia, and it was noted by the surgeon that the patient had become �as stiff as a board�. The anesthetist noted that the patient’s core body temperature was 39.6o C and seemed to be rising rapidly.
- What caused the patient to become �stiff as a board�?
- What could account for the patient’s rapid rise in temperature?
The halothane anesthesia was terminated, and the patient was cooled.
- Dantrolene inhibits the release of calcium from the sarcoplasmic reticulum. Explain how this would reverse the patient’s hyperthermia.
Laboratory results indicated the presence of respiratory and metabolic acidosis, hyperkalemia, and the elevation of blood lactate and pyruvate.
- Explain these laboratory results