Part I – The Symptoms
Imagine that you work at the medical examiner’s officer for a major metropolitan city. As Chief Medical Officer, you investigate suspicious deaths and provide toxicology services for the county. Unfortunately, it’s been a busy week. In the past five days, seven people have died, all with similar symptoms. It is your job to examine the data and determine the 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 sttufy nose and sore throat. they gave her an extra strength Tylenol and sent her back to bed. At 7 am the next morning, the parents discovered that the girl had collapsed on the bathroom floor. An ambulance rushed the girl to a nearby hospital, where she was pronounced dead.
That same day, paramedics found the second victim unconscious on his kitchen floor after what they thought was an apparent heart attack. Sadly, the victim’s brother and fiancée also collapsed later that night while the family gathered to mourn his passing. Both had taken Tylenol to help them cope with their loss shortly before collapsing; neither survived.
In the next four days, four other similar deaths were reported, all in the same neighborhood and all with similar symptoms. Are these seven deaths related? What is causing these people to die? It is your job to answer these questions before more deaths are reported.
Symptoms exhibited by most patients:
Most deaths were very rapid, occurring within a few hours of symptoms.
Questions
Part II – Autopsy Report
Questions
Part III – Subcellular Metabolite Analysis
Detailed analysis of the damaged cells showed that ATP levels in the mitochondria were very low. Levels of pyruvate and acetyl coenzyme A (CoA) were normal. You begin to suspect a malfunction of a specific cellular metabolic pathway and so you request a more detailed analysis of the sub-cellular components of the affected cells from the autopsy. the levels of key metabolites are reported below:
Metabolite |
Average Patient Levels |
Normal Levels |
Glucose |
99 μM |
100 µM |
Pyruvate |
27 µM |
25 µM |
NAD+ |
10 µM |
75 µM |
NADH |
400 µM |
50 µM |
Questions
Part IV – Role of Cyanide
You are now convinced that you know the cause of death for these victims and quickly report it back to the police as this is a very dangerous situation. After realizing that the electron transport chain was no longer functioning, you started to suspect poisoning and ran a blood test for various poisons that you knew a~ ected the electron transport
chain. 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 ~nal electron acceptor.
Questions