Part I – A Very Bad Day

“Doctor, come quickly. We’re losing the patient!” “Losing the patient? How can we be losing the patient? I’m still scrubbing!” Dr. Lopez walked into the operating room. “John, what’s going on?”

“Glad you’re here, Adriana. We could use a hand. Tis patient is not happy with the anesthetic.” John Wilson, the anesthesiologist, was hovering over the patient’s head and giving orders to nurses nearby. Adriana Lopez, an orthopedic surgeon, surveyed the scene. Tis patient was here for minor surgery. He had been

complaining of knee pain. As a seasoned athlete herself, Dr. Lopez had agreed to “clean up” some loose connective

tissue in the patient’s knee – the result of an old injury. Dr. Lopez couldn’t believe what she was seeing. Te patient was rigid and his skin looked patchy; in some places it was almost blue. “How are his vitals?”

“Breathing is rapid, heart rate at 120, pressure is 60/56 and his temperature is 106.”

Adriana quickly made her way to the head of the table. “How can I help?” Te doctors consulted and a furry of activity flled the room. In the corner of the room, a small 18-year-old girl stood staring at the scene. She was pale as a ghost. Softly, two

questions drifted from her corner to the doctors. “What’s wrong with that man? Is he going to die?”

Assignment 1

1. Fill in the chart below. Use “+” if the patient’s vital sign is higher than normal, “−” if the sign is lower than normal, or “x” if the sign is normal. If you need to, use your text or another resource to determine normal values.
2. you were the doctors on the scene, what diagnosis would you give this patient? (You may use the internet to help diagnose the patient.)
3. Jot down some notes about your diagnosis, and bring these to class with you for discussion.

Part II – A Veritable Metabolic Storm

Both doctors turned to the corner to see Emily, Dr. Wilson’s niece. She was visiting the hospital as an assignment for her high school biology class. She was supposed to be shadowing a doctor for the day, and would need to report back to her class with what she saw and did.

“Emily, why don’t you come over here and I will explain what is going on.”

Emily gave her uncle a tentative look and crossed the room. She stood several feet away from the table, not wanting to look at the patient. After several minutes, which seemed to last for hours, the activity in the room slowed down and the doctors gave the nurses a few simple instructions. Te man would survive.

John, Emily’s uncle, spoke frst. “Tis patient just had a bad reaction to the anesthetic. His temperature rose very

rapidly, which can be dangerous to your organs. Te same sort of thing can happen when you have a bad fever.

We just removed the anesthetic and are bringing his temperature back down. Tis condition is called malignant

hyperthermia, and, yes, people can and have died from it. Fortunately, today we caught the problem in time and I

think we moved quickly enough to prevent any permanent problems. We won’t be doing this surgery today.”

Emily looked at her uncle in disbelief. Malignant hyperthermia? Tis man could have died? She never thought

shadowing an anesthesiologist would be so…exciting? terrifying? She wasn’t sure what exactly, but she was sure her

class would love the story.

She looked at the doctors. “What causes malignant hyperthermia?”

Te doctors looked at each other. “John, I think this question is for you. If you don’t need me, I think I will go question the family for a bit more of their medical history and to warn them that genetics are a factor here—they may want to report this to their general practitioners in the future.” With a wink and a wave to Emily, Dr. Lopez left the operating room. Behind her, the nurses began wheeling the patient out of the operating room and into the recovery room.

Emily looked at her uncle, “Well?’

“Malignant hyperthermia is a genetic condition,” he began, “which causes the patient’s temperature to rise to a

dangerously high level when they are exposed to certain anesthetics. Patients with MH also get muscle rigidity,

which is why that poor gentleman looked so stif after I started administering anesthetic. Tey also have changes in

breathing, heart rate, and blood pressure. All of these can be dangerous, but the changes that are seen in muscle are

at the heart of the problem. As the muscles get tense, they also become damaged, which releases chemicals into a

person’s blood stream. As my professor in med. school put it, ‘MH causes a veritable metabolic storm.’”

“A veritable storm?” began Emily. “I’m not sure I get it. Do you have anything I can read that explains the disease in English?” She smiled at her uncle, hoping he got the joke.

“You know what,” her uncle smiled back. “I think I might have some information that will help.”

Clearly, he wasn’t of ended.

Assignment 2

1. groups, review your notes on MH from Assignment 1.
2. Read the following sections of Making Anesthesia Safer: Unraveling the Malignant Hyperthermia Puzzle (available at http://sciencecases.lib.buf alo.edu/cs/admin/Supplemental/UploadFolder/Making_anesthesia_safer.pdf):
• Anesthesia triggers multiple-familial deaths
• e f rst signs
• Serendipitous discovery of an experimental model
2. the above article, what is the “veritable metabolic storm” that the author refers to? What molecular changes are reported in pig muscles during a MH state?
3. Review muscle contraction. Send one person in your group to collect the “Steps of Muscle Contraction” cards from your instructor. In your group, arrange these cards in correct order to represent what happens during muscle contraction.
5. When you have placed all the cards in correct order, prepare a list (below) of the steps that require ATP or Ca2+.
• Steps that require ATP:
• Steps that require Ca2+:

Part III – Am I Susceptible?

After a long shift in the operating room, John was catching a few winks on a bed in the hospital. He was just drifting of when his cell phone rang loudly in his pocket.

“Hi Uncle John,” Emily said cheerily. “Do you have a second?’

“For you, anything,” John replied, sitting up.

Emily began, “I was telling a friend about my time at the hospital and she asked me a question I didn’t know the answer to. I read the information you gave me and the answer wasn’t there either. We were wondering, how do you know if you have malignant hyperthermia? You don’t fnd out the frst time you have surgery, do you?”

John smiled. His niece surely was inquisitive and her questions were spot on—he’d swear someday she would be a doctor.

“Well,” he started, “you know the reading I gave you also had information about pigs. In pigs, you can simply give them a little anesthetic and see if their muscles go rigid. Most of the time, when you remove the anesthetic the pig will go on to live a normal life. In humans, though, that technique would be too risky—and that kind of testing in humans is unethical. Instead scientists have come up with a way to test muscle biopsies. Do you know what a biopsy is?”

“Tat’s when a doctor takes a small sample from your body,” Emily said. “Right?”

“Yep,” her uncle replied through a yawn, “Well, there are centers across the U.S. where people who think they may be susceptible can meet with scientists and run some tests. Te scientists take some muscle biopsies, and then put them in a bath with chemicals that are similar to blood. Tey then expose the biopsies to anesthetics and test which muscles contract the most forcibly. From what you know about MH, can you guess which contracts with the most force, healthy muscle or muscle susceptible to MH? You know what, I will mail you some more information on this topic.”

Assignment 3

1. Predict if healthy muscle or muscle with MH will contract with the most force.
2. check you answer to the frst question, read the following sections of Making Anesthesia Safer: Unraveling the Malignant Hyperthermia Puzzle (available athttp://sciencecases.lib.buf alo.edu/cs/admin/Supplemental/ UploadFolder/Making_anesthesia_safer.pdf):
• Working together to discover the triggers
• Predicting susceptibility in humans
• Developing a grading scale
2. Even though screening tests exist, most people aren’t checked for the disease. Why not? What types of people (or what populations) would be most likely to be screened before they had their f rst surgery?

Part IV – Show and Tell

A couple days later, as Emily was preparing for her class presentation, a package arrived in the mail for her. She tore the package open to fnd more information from her uncle, and a short note:

I know your presentation is coming up soon. I thought this would help. Let me know if you have more questions. It was a treat to have you visit me at work. You are welcome to come back and watch anytime. I get the feeling after this visit that we might soon have another doctor in the family.

Love, Uncle John

“Just in time!” Emily cried.

After reading the information, she sat at her desk trying to develop an outline for the presentation. After a few minutes, she realized that what had driven her learning about the disease were the questions she had asked. She decided that questions could guide her presentation, and she settled on an outline for her presentation that focused around the questions listed below.