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NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCEThe Mystery of theSeven Deaths:A Case Study inCellular RespirationbyMichaela A. GazdikBiology DepartmentFerrum College, Ferrum VAPart I â The SymptomsImagine that you work at the medical examinerâs office for a major metropolitan city. As Chief Medical Officer, youinvestigate suspicious deaths and provide toxicology services for the county. Unfortunately, itâs been a busy week. Inthe past five days, seven people have died, all with similar symptoms. It is your job to examine the data and determinethe cause of death for these victims.The first was a 12-year-old girl. Her parents said that she was awake in the middle of the night complaining of a stuffynose and sore throat. They gave her an extra strength Tylenol and sent her back to bed. At 7am the next morning,the parents discovered that the girl had collapsed on the bathroom floor. An ambulance rushed the girl to a nearbyhospital, where she was pronounced dead.That same day, paramedics found the second victim unconscious on his kitchen floor after what they thought was anapparent heart attack. Sadly, the victimâs brother and fiancée also collapsed later that night while the family gatheredto mourn his passing. Both had taken Tylenol to help them cope with their loss shortly before collapsing; neithersurvived.In the next four days, four other similar deaths were reported, all in the same neighborhood and all with similarsymptoms.Are these seven deaths related? What is causing these people to die? It is your job to answer these questions beforemore deaths are reported.Symptoms exhibited by most patients:⢠Dizziness⢠Confusion⢠Headache⢠Shortness of breath/rapid breathing⢠VomitingMost deaths were very rapid, occurring within a few hours of symptoms.Questions1. Are there any similarities or connections between these seven individuals? What questions would you want toask the families to answer these questions?2. In your opinion, are these seven deaths connected? Why or why not?âThe Mystery of the Seven Deathsâ by Michaela A. GazdikPage 1NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCEPart II â Autopsy Reportâ¢â¢â¢â¢Immediate cause of death was hypoxia (suffocation or lack of oxygen).Tissue sections from heart, lung, kidney, and liver all show massive cell death.Staining with specific dyes showed major mitochondrial damage within the affected tissues.Oxygen levels in the patientsâ blood were approximately 110 mm Hg (normal range is 75 â 100 mm Hg).Questions1. Recalling your knowledge of the function of organelles, what function of the cells was interrupted in thesepatients? Could this loss of function lead to the death of these individuals? Why or why not?2. Given the data in the autopsy, were there any reports that seemed inconsistent with the immediate cause ofdeath?âThe Mystery of the Seven Deathsâ by Michaela A. GazdikPage 2NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCEPart III â Subcellular Metabolite AnalysisDetailed analysis of the damaged cells showed that ATP levels in the mitochondria were very low. Levels of pyruvateand acetyl coenzyme A (CoA) were normal. You begin to suspect a malfunction of a specific cellular metabolicpathway and so you request a more detailed analysis of the sub-cellular components of the affected cells from theautopsy. The levels of key metabolites are reported below:Average Metabolite LevelsMetaboliteGlucosePyruvateNAD+NADHAverage Patient Levels99 μM27 μM10 μM400 μMNormal Levels100 μM25 μM75 μM50 μMQuestions1. For each metabolite listed in the table, describe its role in cellular respiration? Are they substrates or products?What is their main function?2. Are there any abnormalities in the levels of these metabolites in the victims? Develop a hypothesis about whichpathway may be affected based on these abnormalities.3. Explain your reasoning for your hypothesis.âThe Mystery of the Seven Deathsâ by Michaela A. GazdikPage 3NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCEPart IV â Role of CyanideYou are now convinced that you know the cause of death for these victims and quickly report it back to the policeas this is a very dangerous situation. After realizing that the electron transport chain was no longer functioning, youstarted to suspect poisoning and ran a blood test for various poisons that you knew affected the electron transportchain. The test of all seven patients came back positive for cyanide. Cyanide irreversibly binds to cytochrome c oxidase(CcOX) of the electron transport chain and prevents the transfer of electrons to oxygen, the final electron acceptor.Questions1. What affect would cyanide have on the electron transport chain and the production of ATP? Explain youranswer.2. Given what you now know about the action of cyanide on cellular respiration, explain why the patients died oflack of oxygen while their blood oxygen levels were normal?3. Would artificial respiration or oxygenation have saved these people? Why or why not?4. Looking back at the information you have about the people before they got sick, can you suggest a possiblesource of the cyanide poisoning? How should public health officials and police respond to this tragedy?ReferencesBaines, A.T., McVey, M., Rybarczyk, B., et al. 2004. Mystery of the toxic flea dip: An interactive approach toteaching aerobic cellular respiration. Cell Biol Edu 3: 62â68.Beck, M., Monroe, S., Prout, L. et al. October 11, 1982. The Tylenol Scare. Newsweek.Bell, R. The Tylenol Terrorist. Tru Crime Library, http://www.trutv.com/library/crime/terrorists_spies/terrorists/tylenol_murders/2.html. Last accessed: Sep 29 2010.Campbell, N.A., Reece, J.B., Taylor, M.R. et al. 2006. Biology Concepts and Connections, 5th edition. PearsonEducation Inc.Jones, M., Bickar, D., Wilson, M. T., Brunori, M., Colosimo, A., and Sarti, P. 1984. A re-examination of thereactions of cyanide with cytochrome c oxidase. Biochem. J. 220: 57â66.Leavesley, H.B., Krishnan, L.L., Prabhakaran, K. et al. 2008. Interaction of cycanide and nitric oxide withcytochrome c oxidase: Implications for acute cyanide toxicity. Toxicological Sciences 101(1): 101â111.Tifft, Susan. October 11, 1982. Poison Madness in the Midwest. Time.â¢Photo in title block © Frank Jr | Fotolia.com. Case copyright held by the National Center for Case Study Teaching in Science,University at Buffalo, State University of New York. Originally published October 13, 2010. Please see our usage guidelines,which outline our policy concerning permissible reproduction of this work.âThe Mystery of the Seven Deathsâ by Michaela A. Gazdik
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