Friday, August 29, 2014

WILTIMS #175: "And the type of disease shall be one..." "Two, Sir!"

Another week down! Boy am I looking forward to catching up on some much needed sleep on this long weekend. It will help that we had another flag football game this afternoon, to ensure I sleep soundly tonight. I still love how into our intramural flag football league my school gets. Nothing releases all the frustration of lectures and studying like some good ol' semi-violent sport. 

TIL: There is no type I autoimmune diseases, only II, III and IV. Autoimmune diseases can be classified according to the corresponding type of hypersensitivity. Type I hypersensitivity is the kind experienced in allergic reactions and no autoimmune disease mimics that mechanism, hence no Type I disease category.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a ridiculously long-winded disease name. Broken down it means a disease caused by the body's own immune system (autoimmune) attacking multiple glands (polyendocrinopathy) which can lead to an infection by candida yeasts (candidiasis) and the wasting (dystrophy) of tissues derived from the outermost germ cell layer (ectodermal). Simple!

WILTIMS #174: ALL the factoids!

TIL: Allergic reactions happen in two discrete phases, one lasting minutes before quickly resolving and a second, delayed response that only begins hours after exposure to the allergen and lasts for additional hours.

Staying on the allergy theme: anyone who knows someone with a severe allergy has heard of an EpiPen, but do you know how they work? The active ingredient in an EpiPen is the eponymous epinephrine, also known as adrenaline*. Epinephrine activates a potent sympathetic response that does two main things to combat allergic anaphylaxis: -1- it restores blood pressure by decreasing vasodilation (widening of blood vessels) and vessel permeability, and -2- it relaxes the smooth muscle of the bronchioles (large airways of the lungs), thus alleviating bronchospasm (airway constriction), wheezing and dyspnea (shortness of breath).

Graft-vs-host disease is the lesser known type of organ transplant rejection where, instead of the host body attacking the foreign organ, the donated tissue, typically bone marrow, attacks the recipient.

Now for the rapid-fire round!

Earlier this week I learned: Trypanosoma brucei is a parasite usually transmitted by the bite of the tsetse fly and causes African trypanosomiasis, also called cyclic sleeping sickness. The infection can cause many symptoms, the most identifiable of which is the disruption of the sleep cycle, resulting in disjointed sleep at night and sudden sleep episodes during the day.

Herpes simplex virus, both HSV-1 which causes cold sores and HSV-2 that causes genital herpes, hides in nerve cell bodies, allowing it to hide from the immune system between flare-ups.

The rise in Cesarean section as opposed to vaginal birth has diminished the exposure of infants to commensal flora. This can allow more dangerous bugs to gain a foothold in environments from which they'd normally be outcompeted.

A liver can grow back from just a few cells so long as the liver's reticular scaffolding remains.

A beer belly results from liver damage resulting in hypoalbuminemia leading to edema.

Alpha-1 antitrypsin deficiency causes seemingly disparate effects in the liver and the lung by affecting the production of a small protein made in the liver and used in the lung, among other places. The protein's accumulation in the liver can cause liver failure, and its absence in the lung robs the respiratory epithelium of elasticity.

*Unlike most drugs that have two names, one proprietary and one generic, epinephrine and adrenaline are actually both generic. An ill-conceived patent attempt on the name "Adrenalin" led the US to adopt epinephrine as the official term for the compound, while British Commonwealth nations use adrenaline.

Wednesday, August 27, 2014

WILTIMS #173: Mulligan?

It was another long day today. Class, club management, errands, studying, and our first standardized patient encounter of the year. In case you don't remember from last year, a standardized patient is a paid actor and expert on being a patient. He or she can play any sort of patient with an amazingly detailed backstory, and then debrief the student (i.e. me) on what they can improve on from the patient's perspective. This includes both intangible things like showing empathy and having a proper presence in the room, to specific critiques like how to better phrase questions, to hands-on advice on how to better perform the physical exam. In later sessions we will also meet with specially trained standardized patients who specialize in teaching things like pelvic and breast exams (think: "Not quite... move your fingers slightly to the left... there's the cervix!").

It still absolutely amazes me how different the experience is from when I'm playing doctor and the standardized patient is playing the helpless ill person, to when the tables turn and the standardized patient becomes a confident instructor and I the hapless student. I need a lot of work on my physical exam and, for better or worse, I get to watch a video of my performance today and critique my methods going forward to prepare for the next encounter in about a month. I don't look forward to watching myself flail, but there's no better way to learn and grow.

I know I promised a plethora of facts today, but I am going to defer one more day, due to exhaustion. Apologies!

TIL: The cardinal signs of inflammation, unchanged for nearly a thousand years, are redness (rubor in Latin), heat (calor), swelling (tumor), and pain (dolor). Shortly thereafter, the great Greek physician Galen added the fifth and final sign, loss of function (functio laesa).

Tuesday, August 26, 2014

WILTIMS #172: A swell day

I learned a whole bunch of interesting things today, but am absolutely exhausted, so here's one to tide you over and hopefully I can make up for it tomorrow.

TIL: Swelling is always found near stressed tissues for a couple reasons: First, if there is physical damage to cells (like after a cut or splinter), the cellular contents spill into the extracellular space and trigger the innate immune system which makes the nearby blood vessels leaky so that white blood cells can get access to the area. The additional fluid flood the area, resulting in swelling of the tissue.

A second mechanism causes swelling of the cells themselves and is due to one of the first outwardly noticeable effects of cellular stress. Biochemical respiration is disrupted, leading to less energy in the form of ATP. The sodium-potassium pump (NaK pump) is one of the most energy-hungry enzymes in the cell and stops to function quickly without full ATP production. Without the pumps, the electrochemical balance of the cell gets wonky and salt builds up in the cells, pulling fluid across the cell membrane, causing the cells to swell.


Monday, August 25, 2014

WILTIMS #171: Trouble in immunologic Eden

TIL: The "original antigenic sin" is a phrase describing a fundamental flaw in the immune system's ability to adapt over time. When the immune system is first exposed to an antigen (bad thingy), it tailors the best possible adaptive response to that threat. The problem is that the threat (be it a bacterium, virus, etc) mutates significantly by the time the person is re-exposed to the same antigen. The immune response, though, doesn't change. It's like you finally learn that Achilles' weakness is his heel and you proceed to keep attacking the heel of every descendant of Achilles that you fight. 

We learned last year that the point of maximal impulse (PMI) is a physical exam finding of the location where you can best feel the beating of the heart through the chest wall. This location is usually at the counterintuitively named apex of the heart along the midclavicular line in the 5th intercostal space. Today we finally learned that the reason we care about this heart measurement is because different pathological processes affect this location differently. Whereas ventricular hypertrophy only changes the magnitude of the PMI, hypervolemic distention of the ventricles will also displace the PMI to the left.

Friday, August 22, 2014

WILTIMS #170: To clot or not to clot...

Ugh. That was fast! Today was our first assessment of the year in the form of an 8AM double-header quiz in pathology and immunology. Could have gone better. But studying yesterday, I realized that pathology is going to be much much better than several of the classes we took last year. It took a year but we're finally learning about disease, which is more readily applicable to patient care. Now maybe I'll be readier for the next quiz... 

TIL: To identify a clotting factors deficiency, you mix the patient's blood with normal blood. Normal blood contains all of the clotting factors so this "mixing study" will normalize the clotting time for the patient's blood. To figure out which precise factor is deficient requires a bit more work. Now, you mix the patient's blood with a samples each lacking one of the factors. Any combination that brought at least some of each clotting factors will also normalize, but when you find a combination where both parts of the mixture are deficient in the same factor, the clotting tune will remain abnormal, thus identifying the deficient clotting factor.

Disseminated intravascular coagulation (DIC) sucks. This is a condition brought about by a whole slew of etiologies and whatever you do to treat it will make it worse. DIC causes a widespread activation of the coagulation cascade, resulting in small blood clots blocking small arteries and capillaries throughout the body. The clot storm is so severe though that it uses up all of the clotting machinery resulting in widespread bleeding elsewhere in the body. If you treat the clotting with anticoagulant meds, the patient will bleed out; if you treat the bleeding with clotting factors they'll thrombose, likely leading to an embolism. Yay! The treatment is to try to fix the underlying condition but between 10 and 50% of patients with DIC will die from the condition.

Thursday, August 21, 2014

WILTIMS #169: Triadactyl

8AM quiz tomorrow, so today's post will be brief.

TIL: Virchow's triad is the collection of three general causes of thrombosis (blood clots in bad places). They are:

Stasis: the disruption or stoppage of blood flow
Endothelial injury: damage to the lining of blood vessels
Hypercoagulability: extra clot-y blood
Thrombosis is dangerous because the blood clots can break away from their site of formation and cause an embolism (blockage of a blood vessel). The most common place that the clot fragment will settle is in the lungs. This can be very dangerous. The only placebo controlled study ever performed on pulmonary embolisms (PEs) showed such a high fatality rate (26%) that any repeat study would be deemed unethical.

Wednesday, August 20, 2014

WILTIMS #168: Did you mean energy?

TIL: Anergy is a word. I swear I stared at that slide for five minutes trying to figure out if it was a super prominent typo or a word I had never seen. Turns out its the latter. Anergy is essentially the opposite of an allergy. Where an allergy is an overreaction by the immune system, anergy is the lack of an immune response. Anergy can be helpful in telling the body not to attack itself, but can also lead to an immunodeficient state if it is trained not to attack actual pathogens.

Secondly, Listeria is one frightenly persistent bug. Generally, when the body finds a bacterium swimming around in its fluids, it sends macrophages to go phagocytize (eat) and digest it. It then uses the fragments to train the adaptive immune system to hunt down and find any more of those bacteria that might be around. But Listeria has found an escape route. If a bacterium can escape the vesicles that the macrophages use to trap and digest them, they can live in the cytoplasm. Listeria can secrete an enzyme called hemolysin and dissolve the walls of its prison cell.

The body will (usually) still be able to overcome this tactic by recruiting other macrophages and immune cells to kill the infected macrophage, releasing the bacteria back into the body fluid to be again attacked and engulfed, hopefully with better results.

Lastly, the drug atropine is derived from the belladonna plant. Belladonna literally means "fair lady" and was named so because it (among other things) would dilate the eyes, which was a desirable trait in 18th century Italy.

WILTIMS #167: Nutmeg

TIL: I actually learned this one last week, but forgot to share. Luck would have it that it came up again today and I learned a bit more.

The image to the right shows a "nutmeg liver" next to a chunk of raw nutmeg. The problem with this attempt at descriptive naming is that, if you're like me (or anyone unfamiliar with spice preparation) you have no idea what unground nutmeg looks like. I only assume the nutmeg is in the upper left because, at this scale, if that were the liver then nutmeg is naturally the size of a small car.

Anyways, nutmeg liver is usually caused by chronic right ventricular heart failure. Left heart failure generally causes pulmonary edema (fluid in the lungs) because the heart is having a hard time pumping blood out to the body. When the right ventricle weakens, the heart is struggling to perfuse the lungs and blood piles up in the veins. Think of it like when the George Washington Bridge grinds to a halt: every town upstream of the affected side of the bridge gets traffic congestion, but the most affected region will be the closest town to the bridge. The liver is the Fort Lee of the venous system and when blood backs up it puts pressure on the tiny veins in the hepatic tissue. This slowly dilates the venules and small veins of the liver, creating the "nutmeg-esque" look.

If this process happened faster, the tissue would be likely to simply die, but the slow chronic build-up allows the liver to adapt. The process is theoretically reversible through the removal of the downstream blockage, but congestive heart failure isn't a simple problem to address, so this nutmeg-y omen is often a harbinger of bad things to come.

Tuesday, August 19, 2014

WILTIMS #166: Highlighter Syndrome

This is turning into a pet peeve of mine: our pharmacology course director has a habit of sequentially highlighting every. Single . WORD. Sure, he never forgets to mention anything, but I'm so distracted by the lack of logic in his color choices that I stop paying attention.


Moving on.

At some point in one of our pharm lectures today, the Janus kinase (or JAK) was used as an example. Intrigued by the apparent devine reference I Googled the enzyme to learn it's etymology. TIL, JAK was always this enzyme's acronym, but the very apt Janus moniker was an afterthought. Initially the members of this enzyme class were known as Just Another Kinase I and II or JAK I/II. Classic biologist naming eccentricities, but atypically, they quite elegantly renamed these kinases to after the two-faced Roman god.

Janus is one of the few unique gods of the generally Greek-derived Roman pantheon. He is the god of transitions and is often used to symbolize dichotomies due to his two-faced appearance. The Janus kinase takes this name because it contains two kinase domains: one readily phosphorylates substrates while the other turns off the first.

Next, it can be useful to have a really bad, poorly-binding agonist (enzyme promoter) to be used as a long term antagonist (enzyme demoter) because you avoid upregulation (creating more enzymes). Let's break this down a bit: If you want a drug that turns off a particular enzyme, you might try... well... turning off the enzyme. The problem is the body is too smart for that and will respond by producing more and more enzymes. Eventually you can't overcome the upregulation.

So instead, you can use a chemical that actually promotes the enzyme, but way less effectively than the body's natural promoters. This, in effect, slows down the enzyme. And if the chemical binds weakly enough, it won't actually trigger the production of more enzymes.

Lastly, there is hope of creating a cancer vaccine by selectively turning off part of the safety mechanism that the body uses to make sure that the T cells of the immune system don't target the body's own cells.

Saturday, August 16, 2014

WILTIMS #165: One week down?

That can't only have been a week. I am already mentally and even physically exhausted. Yay med school!

One of the more counterintuitive concepts we've learned so far in pharmacology is that the urine excretion percentage of an unaltered drug is actually proportional to the bioavailability of the drug. Put more simply, the more of a raw drug you pee out, the more of it you probably were able to use.

For example, if you give two drugs and find a ton of one in the person's urine, you would generally assume that that one was used less than the one that isn't showing up in the urine. But actually, if only a little of the drug comes out in someone's urine, then it was probably quickly and heavily metabolized (and inactivated). The inactive products of that metabolism would then be peed out on their own. The presence of lots of intact drug in the urine means the drug was probably available for use while in the circulation.

TIL: One of the reasons you shouldn't take Tylenol with alcohol is that alcohol activates a little-used metabolism pathway for Tylenol that produces a potent toxin.

Thursday, August 14, 2014

WILTIMS #164: My thumb hurts

The ever exciting med school flag football season has started up at my school, and after some crazy team-trading drama, we had our first game today. Predictably, I quickly hurt myself by jamming my thumb into someone's hip while reaching for a flag. Jamming is a technical term...

Later in the game as our artificially high score passed 100, I turned to a teammate and, while still rubbing my sore thumb, exclaimed, "Wow, I think we just broke three digits!"

I immediately knew I should have phrased that differently when he looked with a shocked expression down at my hand. Only at a med school flag football game, would he think I was casually commenting on breaking three fingers.

TIL: Red blood cells actually participate in the body's immune response via the complement system. Though they have no nucleus and are generally pretty useless, red blood cells express complement receptors which can bind to antigen fragments and bring them to the liver or spleen, where they are taken up by macrophages for incorporation into the adaptive immune response.

Of course, red blood cells also cause the immune system some problems too; they do not have the ability that most other cells do that tells the immune system they are infected. It's like a bank without a silent alarm and malaria is the crook that has cased the joint. Once inside, malaria is invisible to the immune police. The silent alarm in this case is major histocompatibility complex (MHC) class II, which displays pieces of an infectious agent, alerting the immune system to the infection (and begging for a mercy killing).

Also, it is loosely estimated that there is a 1% decrease in renal function per year after the age of 25. Woohoo, still 98% functioning!

WILTIMS #163: ♪♫♪ Always look on the bright side of death... ♫♪♫

Today was the fourth introductory class of the week with the inaugural microbiology/immunology lecture. The professor took an hour to go over all the ways that micro inserts itself into current events. By the end of that period, I was pretty convinced that we were all going to die tomorrow of excruciatingly painful infections transmitted by bugs, bats, people, poultry and everything I eat.

This afternoon there was an optional talk by our chancellor on the history of eugenics and the ethics of medicine performed during the holocaust. It was a wonderful, if depressing, presentation. The takeaway was not to write off these travesties because they, the Nazis, did it and we, wholesome Americans, would never do such things. Eugenics was born out of science and championed by the US and Britain. They sent delegations to copy our state laws on involuntary sterilization. Germany just took our ideas to one logical (though horrific) endpoint. 

And doctors were some of the worst offenders. German doctors were the first to fulfil Hitlers mandate to euthanize undesirables by starving children. When this bothered some of the doctors' sensibilities, they devised a system to trick patients into a large tile room with a fake showerhead that would release carbon monoxide for a faster, less painful mass-killing. When war broke out on the eastern front and Germany needed a way to kill of millions of people, they simply scaled up the design and borrowed the British concept of concentration camps to store the condemned. The lucky ones were kept alive for medical research purposes.

Like I said, not exactly an upbeat discussion, but a fascinating look at the skeletons in all of our closets. One unsettling thought with which I came away was that though we no longer accept eugenics as an acceptable practice, the basic idea behind the science is still sound. We do pay a price as a society for being compassionate toward the sick, elderly and incarcerated. We could make stronger, smarter, and more pleasant people. We are ok with that in every other species. Why do you think dogs love us and look so weird? Why are horses so good a running and bad at everything else? We did animal-eugenics on them.

But I'd argue that part of what defines our species (at least in this century) is our compassion for everyone, especially the icky parts of society. We could help evolution to advance our species but we choose not to. We'll take the slow path to perfection, if needed. 


TIL: Most people that die from the flu actually die more specifically from secondary pneumonia. The lungs normally are covered in ciliated epithelium that pushes bacteria-ridden mucous out of the respiratory tract and into the esophagus. The flu damages this tissue and allows infectious microbes to flourish in the normally sterile lungs.

Toll-like receptor 4 (TLR4), found on the surface of macrophages, reacts to lipopolysaccharides.

Tuesday, August 12, 2014

WILTIMS #162: Clicking justified

One of the major changes between first and second year at our school is a shift away from purely lecture guided learning (though there is certainly still plenty of that) and towards self-study. The idea being that our professors guide us through the big points but we learn how to best use our time for filling in the gaps. I sometimes feel like we should get some of our tuition back if we're teaching ourselves, but the general idea is sound. We are entering a profession that is constantly changing and we will need to teach ourselves for decades after we graduate.

An interesting change for me is that everything I wrote about last year on this blog I learned in lecture. The few members of my class that for whatever reason read my blog in the past almost always had heard the same anecdotes that day in class. This year, there will be things I find on my own, based on my own study schedule and resources. I'm sure when we start clerkships next year, the trend will only continue. In other words, I think I just justified the crazy trips I so often take down the Wikipedia rabbit hole.

TIL: Amyloidosis is diagnosed by applying a Congo red dye to a tissue biopsy of the affected organ (often the kidney) and looking for an apple-green birefringence under polarized light. Birefringence is a special property of a material whereby it can split a beam of light depending on its polarization and direction. Using a complicated polarisation technique on a pathology slide, substances with these properties will shine bright green while the rest of the field is black.

WILTIMS #161: Med School Strikes Back

If first year is the study of the normal body, second year is the study of everything that can go wrong and, if possible, how to treat it. We learn all of these topics first generally, and then organ system by organ system, as pathology/pathophysiology, microbiology/immunology, and pharmacology. ALL the -ologies!

It was surprisingly rough getting back into the swing of things today, even though we didn't learn much in the way of material yet. But as I dust of the mental cobwebs, I remember back to last year, and can barely believe how far I've come.

"Walk this way..."
Last week I helped out with the new first-years' orientation week. In between panels and walking lost students to their lockers, my classmates and I all agreed that it was so refreshing to see students before their spirits are broken by that first couple weeks of lecture - back when the biggest problems were deciding between buying or renting a microscope and finding the nearest grocery store. We quickly learned that these worries were easily drowned out by the flood of information we were being fed. And then we realized that that first test was a laugh compared to the second - and anatomy/histology was a cakewalk compared to even early physiology/biochemistry - and the cardio exam was at a whole 'nother level... and so on.

By the time summer rolled around we understood: med school never gets easier, it only changes form and/or gets harder. But every victory reassured us that we would survive the next challenge. Every "pass" on an exam showed that we had improved beyond our own wildest expectations from just a few months before.

So when today we heard that this would be the hardest semester yet (until the next, that is) and that all of this was a prelude to the ever looming USMLE Step 1 board exam at the end of the year, I could confidently shrug it off. Looking at the lost first-years in whose shoes we stood 12 months ago, I can't wait to see where we stand 10 months from now as we transition to clerkships. Bring it.

Today I Learned (TIL):
Stopping oral steroids cold turkey can be deadly due to adrenal insufficiency.

Hypertrophy is the abnormal growth of a tissue by increasing cell size, as compared to hyperplasia which is abnormal growth due to the production of additional cells. The term atrophy covers the opposite of both hypertrophy and hyperplasia. Metaplasia is the change from one cell type to another. When any sort of change leads to negative enough consequences, it can be called a dysplasia. Dysplasias are reversible, whereas carcinomas (cancers) are not.

Caseous necrosis is the type of cell death seen in tuberculosis. It is named for its morphologic similarity to cheese (latin: caseus = cheese).

Sunday, August 10, 2014

Last Last Summer Post

Phew! Summer just flew by and I have next to no blog posts to show for it. Apologies. The situation will correct itself come Monday when I start second year.

Interspersed with three weddings, a graduation, two trips to the west coast, and moving essentially twice to the Bronx, I have been taking part in a summer research program in the Pediatric Intensive Care Unit at our school's nearby teaching hospital. As I wrote in my previous post, the experience began abruptly and with little formal orientation. At the time it was absolutely terrifying and the trend of frantically scrambling through my ignorance to meet deadlines never abated. But this frenetic pace was great at pushing me to work and learn when all I really wanted to do was sleep, consume internet memes and allow my brain to regain its natural state of ooze.

Here are some broad takeaways from my dabbling in research:
  • Hospital bureaucracies are vast and vogonic: You not only need to turn in the right forms to the right people, but also with the right attitude and 25 paper copies to get anything done with research. I fully understand that review boards protect patients and subjects alike and are a valuable part of the research process. But it seems that, due to being continually force-fed research that has been spun by the writers to seemingly be the greatest achievements in medicine, some of the people we deal with are so jaded that they deliberately put up roadblocks to innocuous requests because of harmless missteps in protocol.
  • Resident physicians make surprisingly terrible subjects: Residents are newly graduated doctors, so they are necessarily smart, science savvy and knowledgeable about the benefits of research. However, they are also super-crazy busy and asking them to do even the most innocuous task might seemingly break their very tenuous hold on sanity. Our project required maybe 15 seconds of each resident once every few days. We went out of our way to position everything as conveniently as is humanly possible. Despite all of our conciliatory efforts, a month and a half into the study we only have about 50% participation, a number with which my adviser is actually really pleased.
  • Residents are amazing: I got to work with a couple of residents on my project and it was absolutely incredible that they could manage extracurricular research on top of the 16-hour shifts (which rarely ended on time). These are doctors but they barely know what they're doing and yet they are directly responsible for the lives of direly ill children (don't worry, they have lots of supervision). The couple times I attended morning rounds in the PICU, it was amazing watching the residents present their patients to the attending. They can typically hit 95% of the important facts but they are always learning to be better. And there is so much to learn.
  • Attendings are amazing, and I want to be one: And on the receiving end of rounds are the attendings, the real doctors. These are the board certified head honchos of the hospital world. They are responsible for everything the residents do and learn. And when things go wrong, not that the residents could have prevented the wrong-going, the residents and nurses call in the scrub-wearing cavalry. Seeing the attendings go to work is amazing, especially in the acute settings that the PICU provides, in part because of the calm way that they take charge of potentially chaotic situations. This is what entices me about critical care and has put this rather vague sub-specialty high on my list of potential careers.
Overall, I had a great time with this summer opportunity and though this is the end of my core involvement with the project, I will be doing small and eventually bigger things with this research in the coming years. If you are a frequent reader of this blog, expect periodic updates as the project progresses.

Now I'm off to enjoy the last stress-free night's sleep of summer! I'm looking forward to (and already planning out) my first post of the year for tomorrow night. See you then!*

*I will not see you and you will not see me, but you might read more words that I have haphazardly collected in blog form.