Steps of neuromuscular transmission

Study 1
Derek Zoolander is a 32-year-old fashion model for a world famous modeling agency. Over the last 8 months, he experienced "strange" symptoms. He had severe eyestrain when he modeled for longer than 15 minutes. He became tired when he did common tasks, such as eating, and he had extreme fatigue on the job. Despite his strong work ethic, Derek had to excuse himself from several photo shoots because he simply could not pose. Derek is not a complainer, but he began to worry about these vague symptoms. His physician suspected myasthenia gravis. While awaiting the results of a serum antibody test, the physician initiated a trial of an acetylcholinesterase inhibitor. Derek immediately felt better while taking the drug; his strength returned and he could work normally. Meanwhile, the results of the antibody test were
positive, confirming the diagnosis of myasthenia gravis.

1. What are the steps of neuromuscular transmission?
2. What step of neuromuscular transmission is blocked by myasthenia gravis (review pages 86-87 in Guyton and Hall)?
3. Explain why muscle weakness occurs in myasthenia gravis.
4. How does curare compare to myasthenia gravis in action?

Study 2
Your patient is a 56-year-old office manager who is significantly overweight. His diet consists of fatty foods that included red meats and high-calorie desserts. He had occasional chest pains that were relieved by nitroglycerin.
One night, he went to bed early because he wasn't feeling well. He awakened at 4:00 A.M. with crushing pressure in his chest and pain radiating down his left arm that was not relieved by nitroglycerin. He was nauseated and sweating profusely. He also had dyspnea, especially when he was in the recumbent position. His wife stated his breathing was "noisy." He called 911. The paramedics arrived and transported him to the nearest hospital.
In the emergency department, his blood pressure was 105/80. Inspiratory rales were present, consistent with pulmonary edema, and his skin was cold and clammy. Successive electrocardiograms and lab results of cardiac enzymes (creatine phosphokinase and lactate dehydrogenase) suggested a left ventricular wall myocardial infarction. His heart rate was variable during the sequential ECGs. His heart rate was 116 bpm during the first recording and 80 during the last recording. During cardiac catheterization, pulmonary capillary wedge pressure was 32 mm Hg (normal, 5 mm Hg). His ejection fraction, measured was 0.35 (normal, 0.55). His stroke volume was measured at 38 mL (normal range is 50-80 mL).

5. Why did he suffer orthopnea (difficulty breathing while recumbent)? Why would pulmonary edema be worse while lying supine compared to sitting or standing?
6. Why did pulmonary edema develop? Elaborate on the major Starling forces involved after reviewing pages 181-186 of Guyton and Hall.
7. Which information in the case tells you that his stroke volume was decreased?
8. Assuming that the patients decreased stroke volume was consistent from the first ECG measurement until the cardiac catheterization, what were his cardiac output measurements during the ECG readings?
9. The normal range for cardiac output is between 4.0 – 8.0 L/min. Were his measurements within normal range? What is the result of a low cardiac output on circulation?
10. Using the blood pressure measured in the emergency department, what is his mean arterial pressure and pulse pressure.
11. Why is mean arterial pressure not the simple average of systolic and diastolic pressures?