WILTIMS #68: Myasthenia gravis

Apologies for the brief post this evening; the SO is in town and takes precedent. I will give you this sunset picture I took yesterday as some little recompense.

TIL: Myasthenia gravis is a rare autoimmune disease whereby the body attacks a specific postsynaptic receptor at neuromuscular junctions. This means that the nerves send neurotransmitters to the muscles telling them to contract, but the muscles gradually lose their ability to recognize this signal. The result of this is the very slow cumulative debilitation of muscle strength. It is often first noticed as an eye condition, because the muscles of the eye are very fine tuned and are easily affected. Untreated, it can progress to near paralysis.

The most amazing thing about the disease is the treatment. An acetylcholinesterase inhibitor is administered which causes the neurotransmitters released by the nerve to stick around longer, amplifying the signal to the muscle and reversing the condition (at least for a while). This was seen as a miracle drug when it was first used for this disease because it is able to turn a bedridden patient into a normal healthy person within seconds.

WILTIMS #67: Ickle Sickle Pickle

In a refreshing reminder that we are adults (and occasionally treated accordingly), we had homework due today that we were simply trusted to have completed. We then had an intelligent student led discussion of the answers, with the people who researched the most complete responses to questions supplementing the answers of others. A smidge of my faith in my fellow classmates has been restored.

TIL: Sickle cell anemia is caused by the substitution of one amino acid (the building blocks of proteins) for another in the beta globin subunit of hemoglobin (the protein in red blood cells that carries oxygen from your lungs to your tissues). The mutant hemoglobin can bind with other hemoglobin proteins, resulting in polymerization. These aggregations of hemoglobin cause the red blood cells (RBCs) to become deformed (hence the sickle cell name) and get stuck in the narrow capillary blood vessels of the body. The tissues become deoxygenated due to the RBCs piling up causing damage and pain.

The body also quickly attacks these sickle cells in the spleen, the body's quality control center for blood cells resulting in anemia and the bone marrow can't replenish RBCs fast enough. The spleen often gets infected due to damage and overwork from this process.

The only cure is a bone marrow transplant, which replaces the stem cells that create the mutant RBCs. Other treatment options include blood transfusions (to swap out bad cells for good), antibiotics (to fight infection in the spleen), erythropoietin (to spur RBC production to combat the anemia), and the administration of the anti-tumor drug hydroxyurea which promotes the production of fetal hemoglobin (which cannot aggregate like the mutant adult hemoglobin).

WILTIMS #66: I'm ready. I'm ready. I'm ready. I'm ready.

The grades are in and I officially passed my first block! Huzzah!

We covered mostly review topics today with a heavy emphasis on thermodynamics (yuck!), so instead I'll share some insights from Sunday when I shadowed an OB/GYN resident at the medical center for the day.

When I arrived on the unit at 7 am, the resident that I was following had already been there since 10pm the previous night. By the time I left, exhausted even after doing very little, she was still writing up reports over 19 hours into her 16 hour shift. Oh yeah, and she was 7 months pregnant herself. Fun!

To borrow a saying, OB seems like hours of boredom punctuated by minutes of sheer terror.

How's room 3 coming along? 

-2 cm

How about now?

-3 cm 

 

Room 3?

-5 cm and in some discomfort

PUSH NOW!!!

My exciting experiences for the day included helping with a delivery (I held the mother's right leg) and watching a cervical cerclage procedure. I was complimented by the nurses for not passing out watching my first vaginal delivery. Woot!

A cerclage is the surgical suturing closed of the cervix. This procedure is done when an expecting woman has cervical incompetence, which can result in midterm miscarriages unless corrected. The suture is then taken out at about 8½ months, after the most dangerous period has passed.

WILTIMS #65: Grr. Argh.

Don't be a zombie! Eating brains is bad. We got to watch NOVA in class and it was as engaging as ever (albeit a bit dated in this case). The episode was on transmissible spongiform encephalopathies, such as scrapie (in sheep), mad cow disease (in... cattle) and Creutzfeldt–Jakob disease (in humans).

Normal prion protein on the left, mutant on the right.

These diseases are terrifying, as is their cause. Each disease is transmitted in one way: through the cannibalistic consumption of the brains of members of one's own species. The only exception is that certain forms of the disease can cross into other species, again, when brains are consumed. This was a major concern in Britain where the seemingly harmless sheep scrapie, which cannot transfer to humans, was introduced to cows, which were routinely fed protein supplement made from the ground remains of other cows and sheep. Once cows became infected, the toxin spread wildly through the same feed due to the cow component.

Creutzfeldt–Jakob disease (CJD) in humans was known to spontaneously arise very infrequently, causing the same symptoms seen in all other mammals. The patient rapidly loses motor coordination and then becomes progressively more demented, before dying within months. These spongiform encephalopathies are so named because the brain (encephalon) takes on a spongy appearance during autopsy do to the formation of many holes in the brain tissue. The disease progresses as more and more of the brain is consumed. There is no treatment. In the early nineties, people began coming down with a slightly different form of CJD, widely believed to have come from the the bovine disease that was transmitted through contaminated meat.

The biochemical cause of spongiform encephalopathy is very zombie-like. There is a normal version of a certain protein that is found in all healthy individuals. The disease is caused when a bad version of the protein is introduced that is able to bind with its healthy form in such a way so as to convert the normal form into the diseased form. It doesn't actually change the transcript of the protein. The order of the amino acids remains the same; the protein is merely folded differently. This causes a chain reaction that forms plaques of the aggregated diseased protein that build up and damage the surrounding tissue.

The protein can't be killed, because it's not alive and it is incredibly resistant to degradation, even when irradiated, burned and buried. Sleep well tonight!

TIL: There are protein motifs called "zinc fingers" formed by a zinc-stabilized hairpin turn. 

Epidermolysis bullosa is a disease resulting from the malformation of the keratin protein that results in incredibly fragile skin that blisters at even the softest touch.

Ehlers–Danlos syndrome is a collection of disorders caused by the mutation of genes involved in the organization of collagen. Collagen is the most abundant protein in the body and is generally found in connective tissue, providing a measure of flexible stability. Persons with this disease show many diverse symptoms, but a couple classic signs are of hyperflexible joints and stretchy skin that can be easily pulled away from the body.

WILTIMS #64: Curse your sudden but inevitable betrayal

View the reference here

Me: This block is going to get pretty interesting...

Mal: Define interesting.

Wash: [Deadpan] Oh god, oh god, we're all gonna die?

____________________________________________

I'll start this new block of medical school with a quote from our professor and course director for physiology: “Weekends are a concept, not a reality."

Having moved away from anatomy, we are no longer taught by MDs but rather PhDs. I sometimes wonder if these folks are gluttons for pain. During undergrad, I always felt bad for scientific researchers teaching premed classes because, not only are premeds inherently incredibly annoying students, but the professors always seemed disappointed that we weren't choosing to go into their field. But the professors that we met today, both in physiology and biochemistry, have truly embraced the medical field and found ways of finding clinical correlations for even the most basic (or acidic) material.(Thank you, thank you, I'm here every night)

TIL: There are 20 standard amino acids that make up nearly every piece of every protein in all of life. There are only two exceptions which take the form of "non-canonical" amino acids. One, pyrrolysine, is only found in certain single-celled organisms. The other, selenocysteine (pictured on the left), is used in only 25 of the 10⁵-10⁷ proteins that the human genome encodes.

Homeostatic variables are physiological features that our body is trying to keep within a narrow range, like temperature, pH and blood pressure. Heart rate is not a  homeostatic variable because the body wants the HR to change depending on the circumstances, usually to manage one of the other true homeostatic variables.

Whereas feedback regulation is the body's response to a perceived change, feedforward regulation is the preemptive response to a predicted stimulus. Metaphorically, feedforward regulation is looking up the weather forecast and deciding to bring an umbrella; feedback regulation is walking outside, noticing it's raining, and then going back to get the umbrella.

WILTIMS #63: End of Block 1

My official embroidered white coat finally arrived!

It's been a long blur, but the first block of medical school is over! I feel like I've learned so much; yet, it's amazing how much is left to tackle. But the most important thing that I've learned so far is that I really do belong here. It hasn't been easy (and according to the 2nd, 3rd and 4th years it will only get progressively worse), but I'm going to make it through. On to the next course!

TIL: The posterior cricoarytenoid muscles are the sole abductors of the vocal cords. These are the only muscles that open the vocal folds within the trachea, allowing for unimpeded airflow. All of the other intrinsic muscles of the larynx either bring the vocal cords together, allowing them to make sound, or change the length and thickness of the cords to change the pitch.

All but one of these muscles (the cricothyroid muscle) is innervated by the recurrent laryngeal nerve. If you've been following this blog closely from the get go, you may remember the recurrent laryngeal nerve as the branch of the vagus nerve that loops around the arch of the aorta for no apparent reason and then heads back up into the neck. Amazing how long it took for us to connect that nerve with its muscles!

WILTIMS #62: The ciliary muscle abides

Last histo lab today! Only one anatomy lab left tomorrow and I'll be officially 1/15th* done with med school!

TIL: [This may sound like medical babble, but I'll have a go at translating it in a sec.] The ciliary muscle of the eye is innervated by parasympathetic fibers of the oculomotor nerve (cranial nerve III). It is well known that the contraction of this muscle results in the accommodation of the eye through the counteraction of zonular fibers, whereby the lens becomes more spherical and decreases the focal length.

Put more simply: When you are relaxed, you brain contracts a muscle that changes the shape of the lens of the eye, causing your eyes to focus closer to your face.

The mechanism for this is not 100% understood, but the best guess is that it works like this: imagine you have a rubber dodgeball held in the center of a pillowcase. Normally, you have 4 super strong people pull on each of the corners of the pillowcase, flattening the pieces of cloth against each other and squishing the ball inside so that it's no longer round. All this tension makes you uneasy, so you send in a strong but relaxing guy (think The Dude from The Big Lebowski) and have him pull on one of the flat surfaces of the pillow case. This counteracts some of the tension from the folks pulling from the corners and allows the ball to get a little rounder again.

That's it! The ball is the lens of the eye, the pillowcase is zonular fibers, and The Dude is the ciliary muscle.

*This block is 3 months of the 4 years of medical school, or 1/4th of 1/4th of medical school. However, since we don't have class for the summer between 1st and 2nd year, we lose a block and are left with 15 3-month segments, of which we have completed one - thus 1/15th.