When Pathology and Chemistry combine, and not always for the better….

[Letonna]

My next series of lectures will be 5 lectures on some odd, bizarre, and rare diseases relating to chemicals and elements. Some genetic, some environmental, and some just human stupidity. All ones I find very interesting from a chemical standpoint.

The golden ring in the eye, a classic symptom of Wilson's

Our first one will be looking as is a disease known as Wilson’s disease, or hepatolenticular degeneration. Known systematically as copper toxicity. It’s a genetic(usually) condition in which the body accumulates a lot of copper. It’s easily diagnosed by taking a bright light and looking into the eye. In someone well into the disease, a bright copper/gold ring will be seen around or in the eye.It's caused by accumulated copper particles that have collected there.

Just about all cases are genetic, and for good reason. Wilson's disease is described as a genetic failure, residing on chromosome 13, that is a multi enzyme failure that results in the failure to metabolize and remove copper. The body keeps absorbing more and more until it reaches dangerous and damaging levels(often by the time the patient is a child, teen or young adult). The most damage is done in the liver and brain.

In the liver, the excess copper act as, what chemist call, a Fenton Reagent. Meaning it turns dioxides(peroxides) into free radicals(which is very very bad). The free radicals destroy everything. DNA, protein, enzymes, membranes. In the brain, the same action happens, but instead accumulates in the very core of the brain, parts needed for learning and cognitive development.

Penicillamine, also known as Cuprimine, a chelation agent

Copper is necessary in a healthy diet. In fact most over the counter multivitamin/multi-mineral tablets have copper in them. It’s necessary for your body to make energy. It’s extremely rare for you to give yourself copper poisoning. Many women even have copper implants to prevent contraception, and people consume large amounts based on the foods they eat.

The basics of the Fenton Reaction

The disease is not a death sentence however. Upon discovery, the patient may undergo what called a chelation therapy. The patient is given intravenous mercaptans(small carbon thiols for those of you who care) like Cuprimine. Avoiding foods like shellfish and mushrooms. In more advanced therapies, using Zinc salts to stimulate different metabolic pathways in the body to rid of heavy metals. In very advanced and severe cases, all the above with possible organ transplant and physical and occupational therapy, as well as psychological treatment for any mental damage.

[Letonna]

Let's talk about Tylenol...

Acetaminophen, also known as MAPAP, APAP, Tylenol, and paracetamol, is an over the counter anti inflammatory and anti fever drug developed in the 1940’s and released in over the counter form in the 1950’s. It came into the market well received, toting the attractive features like: “Well,it’s not aspirin!”, children can take it and have less of a chance of dying(see reye’s syndrome), and you can take a lot of it, all day long forever(we’ll come back to this part in a bit). 

Acetaminophen is so ingrained into modern medicine, it almost seems painful to say to ourselves “You know, maybe this isn’t such a great drug…” Not only is acetaminophen available widely in over the counter items like cough syrup, migraine pills, PMS aids, and nighttime sleep aids. It’s in dozens of prescription pills as well. Vicodin, Midrin, Percocet, Fioricet, Ascomp. It’s everywhere!

The FDA has had solid proof of its toxicity since the 1970’s, but only began tighter regulation in 2009(and again in 2011). Before, the standard max dosage for an adult or adolescent over the age of 12 was 4 grams a day(4000 milligrams). That's 8 extra strength tablets a day. We’ve known for a while that acetaminophen toxicity is the leading cause of liver failure in the USA. Period. Higher than drinking! It's now encouraged not to consume more than 2-3 grams daily by the way.

"Only use as directed" in not big enough quotation marks

Now I’m not going to tell you to not take anything or take anything. I love a Tylenol when I have a headache. The problem truly lies with pain management in America. Everyone knows of the opiate epidemic claiming tons of lives everyday. Most prescription pain killers are opiates, and even more are in formulations that contain Tylenol. Physicians prescribe drugs that are meant to be taken after surgery or during cancer or aids treatments. These drugs not designed to be life long medications. They have the opiate pain killer, but the acetaminophen helps reduce inflammation from a wound or progressive illness. Using these drugs in pain management, when the pain is often neurological, or hard to define, is really pointless.

A liver ravaged by excessive acetaminophen abuse

I know first hand people don’t follow the “one to two every 8 hour rule”. Opiate resistance begins after 3 weeks of regular consumption. Consider someone on pain therapy for a decade. I see people like this on 15-20 of these tablets a day. Now, I’m also not going to say that the problem is doctors, or it’s lazy medicine, or it’s insistence on keeping that yelp review good. I’ll let you decide. I’m just writing these to kill time.

(But the answer is yes.)

What's so baffling to me is what people have said about the dangers over the years. Tylenol first came out as a prescription around the end of WWII. Under pressure of lobbyist, it was released as an over the counter to compete with Bayer and it's pain killer Aspirin. It's believed by many today that if Tylenol were released on a modern market, it would never be available without prescription. It's just been grandfathered(and lobbied) into the peculiar spot it's found itself in now.

[Letonna]

It’s all about those 5 chambered sacs of love! Don’t breath this!

Bronchiolitis obliterans

Diacetyl

Bronchiolitis obliterans, also known more recently as “Popcorn Lung” is a degenerative lung disease caused most often by extreme exposure to compounds called diacetyls. The most simple of the diacetyls is, well,diacetyl(butane 2,3-dione) pictured above. Bronchiolitis obliterans can be caused by other caustic chemicals like amonia and chlorine, but it's most recent cases have involved food additives.

First named in the mid 2000’s due to a rapid rise in lung scarring by workers in the snack food industry. It was later discovered that artificial flavorings and scents of the diacetyl family caused severe and rapid onset of lung degeneration. The FDA, with the knowledge of these issues, and with advice of leading pulmonologists, allowed diacetyl to continue to be used in food additives, although noted it was open to new research.

However, the U.S. OSHA, later in 2010, under pressure from leading doctors, scientists and world health advocates, formally recommended employers to protect workers and consumers from dangerous concentrations of diacetyl.

The disease has reared it’s head in recent years however. It was later found by independent teams of researchers that e-juice (nicotine solution for inhalation) in e-cigarette liquids often contain diacetyl and similar compounds to give the vapor a buttery sweet taste. Many pulmonologists worry that with the vast unregulated manufacturing of nicotine vapor liquids, many more harmful ingredients that could also exacerbate popcorn lung may come up.

There have also been concerns from coffee manufacturers that the processing and manufacture of coffee and coffee flavorings, specifically artificial coffee flavors may lead to degenerative lung conditions. Chemicals like acetaldehyde, acetylpropionyl, acetoin, and furfural.

Beryllosis

What’s with the work related diseases in this lecture. Good thing OSHA and the FDA got our back!

Berylliosis is a rare lung disorder that occurs when beryllium (element number 4, right above magnesium) is inhaled into the lungs. Beryllium is very useful in certain applications, typically in alloys. It’s often seen in aircraft parts because it’s strong and light, and has the tendency to reduce cracks in metal crystals. However, pure beryllium is never used anymore.

Beryllium being such a light element (9 grams per mol for those of you who care), it has the tendency to shed atoms into the air. Keep in mind most of the air you breath is composed of much heavier particles, so beryllium tends to just float around. A cautious observer and A+ student of high school chemistry will be quick to point out beryllium is a metal, not a gas. To which I say: when talking about the obscure elements on the periodic table, ‘metal’ is nothing more than a point of view.

Beryllium is fragile. If you were, say, deep underground. And say, you worked in an era where OSHA didn’t exist, and air circulation was too expensive. You would have a very very good chance of digging into minerals and rocks where beryllium may reside. Such were the fate of many miners, refinery workers, fluorescent lamp manufacturers, and nuclear energy and weapon engineers before the 1990’s.

Because beryllium is so close to calcium, and because it tends to not only have a similar charge (+2), it can ‘gunk’ up spots where magnesium would normally be (in enzymes, DNA, protein). It also has the nasty tendency to not alert your immune system until a lot of damage has been done. Once you body starts to fight it, you quickly amass a large fighting force of T-cells in areas most sensitive to it (your lungs). Cancer is a common end stage of the disease, if pneumonia hasn’t gotten you first.