Saturday, January 25, 2014

WILTIMS #100: Doctoring

Centennial post! Thank you to all of my readers. I love writing this blog (though I do forget this sometimes at 2am) and I'm constantly amazed that anyone would come back on a semi-regular basis to read my ramblings. This was the last day before a big week of tests, so I will probably not post anything for a little while. I have to stay in medical school to keep writing about it!

Today we had a midterm in Fundamentals of Clinical Medicine at 8am(!!!). How younger me ever managed to go to school at such an unsavory hour I do not know. We then continued into three straight hours of medical physiology, which was surprisingly intelligible for once. I then ditched the one hour of class in the afternoon - gasp! - to give a presentation at a local middle school about lung cancer and smoking.

Me getting a radiation treatment
As I mentioned in a post eons ago, I am on the executive board of the Cancer Awareness Education Program student club on campus. Our mission is to go to local middle and high schools and give presentations to kids about the dangers of lung cancer and smoking. At the same time, we are conducting research on the effectiveness of such presentations. Unlike D.A.R.E. programs which focus on peer pressure, "just say no!", and the like, our goal is to teach the science behind anti-smoking claims so that kids can decide for themselves not to smoke rather than just being told not to. Of course, we also add a solid dose of scare tactics, via gross pictures, to hammer the message home (my radiation mask and personal cancer stories do wonders too). Here are some of the highlights for your reference:
    My mask
  • Cancer is the second largest cause of death in the US and lung cancer is far and away the biggest killer of all cancers.
  • Even though slightly more people are diagnosed with prostate and breast cancer each year, lung cancer kills more people than prostate, breast, colon and pancreatic cancers combined.
  • Over 90% of these lung cancer deaths (and most oral and throat cancers too) are directly caused by smoking.
  • Lung cancer is an especially nasty cancer prone to metastasis and has awful, relatively ineffective treatments.
  • Smoking, even if it doesn't cause cancer in an individual, always reduces lung function. 
  • Whereas healthy lungs will last well over 100 years, a lifelong smoker will start to have difficulty breathing by their 50s and their lungs will start to fail by 75. 
  • But by stopping smoking, even after decades, the lungs will return to a normal rate of decay, prolonging the time that they'll work well.
  • So don't start, but if you do, it is never too late to quit!
I love doing outreach like this - sharing the wonders of science and medicine with the uninitiated public. I firmly believe that regardless of education or interests, everyone should have a healthily inquisitive mind. And one of the biggest mysteries that everyone confronts on a daily basis is how their own body works. Part of the reason I write this blog and why I wanted to go into medicine in the first place is to share the knowledge that am lucky enough to learn in medical school with my friends, family and someday my patients. It's your body and it's amazing and you should know that!

The word "doctor" is literally Latin for teacher

TIL: The diving reflex is a physiological response to submersion of the face in cold water causing the lowering of the heart rate and vasoconstriction of peripheral circulation. This reflex allows people, especially young children, to survive for an extended time underwater without breathing.

Thursday, January 23, 2014

WILTIMS #99: Do it in Latin

Today, on top of some surprisingly lucid lectures, we did something new! We had a physiology small group case study lesson which entails the following: we are given a write-up about a patient and asked to think of possible diagnoses; we decide on further tests we would like to order and justify the need for said tests; we are then given the results of the desired tests (see pic below) and are then asked to come up with a final explanation of what is going on with the patient.

It's almost like were doctors! Except that 80% of people got each question wrong the first time around... Hey, we're only 12.5% of the way through med school, so cut us a break!

Important medical gibberish gleamed from the fake tests we ordered on our fake patient

TIL: "Night repair" beauty products must be used at night because they contain vitamin A, which is extremely light sensitive. If applied during the day, the drug becomes intensely active and can cause chemical burns.

The oxidation of polyunsaturated fatty acids is the main cause of the smell associated with spoiled food.

One possible explanation for elderly people always feeling cold is the decreased sensitivity to sympathetic adrenergic neurotransmitters that control vasoconstriction in non-glabrous skin. Rather confusingly, glabrous skin is non-hairy skin and non-glabrous skin is hairy skin. 

Cor bovinum (literally "cow heart") is a term for the massive left ventricular hypertrophy - thickening of the walls of the left side of the heart. As my professor said today, "If you're going to insult your patient, do it in Latin."

WILTIMS #98: Snow day

So today we had a partial snow day that robbed me of most of my potential material...



Yesterday's post was good though! You should go read that one. Again. There'll be a quiz.

TIL: Female steroid hormones (like estrogen) have 18 carbons, male steroids (like testosterone) have 19, others (like progestins, glucocorticoids and mineralocorticoids) have 21.

Dehydroepiandrosterone (DHEA), a very popular anabolic steroid for doping athletes, is produced naturally by the body just prior to and after birth. It then peaks again in the mid-twenties and steadily declines from then on. DHEA is an androgen (sex hormone) precursor and has numerous beneficial side effects (hence the doping), particularly for the elderly who have severely diminished natural production.

Wednesday, January 22, 2014

WILTIMS #97: Über-eases and parentheses

Sorry for the long one today, but if you can navigate all the parentheses, I promise you'll learn a thing or two!

Is there such a thing as a good disease? Dis-ease literally means not-good, so it would appear not. But we don't seem to have a better word for an abnormal genetic variation that is actually beneficial. ApoA1 Milano is an aberrant version of apolipoprotein A1, a protein found in high density lipoproteins (HDL ("good" cholesterol)). The very few people that seem have this version of the protein are seemingly immune to atherosclerosis (the hardening of arterial walls, a main cause of coronary artery disease). These real-life X-men have extremely low amounts of HDL floating around their blood vessels and oodles (that's a scientific term) of triglycerides, but show none of the associated ill-effects. If drug companies can find a way to produce this protein cheaply or get the body to produce it through gene therapy, huge strides could be made in combating our #1 killer, heart disease.

TIL: A related protein to ApoA1, ApoB, is the best example of RNA editing. Both ApoB-100 and ApoB-48 are encoded by the same gene. While ApoB-100 is translated in its entirety in the liver, ApoB-48's RNA transcript is changed by one nucleic acid. This small but important edit changes a codon (nucleic acid triplet that codes for one amino acid of a protein) in the middle of the protoprotein to a stop codon, terminating the protein early, effectively creating a totally different protein from the same DNA code.

Xanthomas on the surface of knees
Familial hypercholesterolemia causes xanthomas, relatively benign collections of fat seen in connective tissue.

Statin drugs inhibit HMG reductase, the enzyme that allows your body to synthesize cholesterol. Don't we need some of that? you might ask. We consume more than enough cholesterol in our diets; statins just stop us from adding our own to the mix. But I suppose if you are starving in a desert somewhere you should probably discontinue your statin prescription.

The coronary circulation (blood vessels supplying nutrients to the muscle or the heart) perfuses the heart tissue very oddly. The epicardium (outer surface of the heart) perfuses during systole (during ventricular contraction (when blood is pushed out of the heart)) which makes sense in the rest of the body, but the endocardium (inner surface) perfuses during diastole (when the ventricles are being refilled but no blood is flowing out of the heart). Though this doesn't seem to make sense at first (How do you get more nutrients from blood that isn't flowing?), it should with a little more explanation.

Whereas the outer surface of heart muscle is essentially at ambient pressure in the chest cavity, the inner surface is put under high pressure (specifically the systolic pressure (~120 mmHg)) every time the heart beats. This high pressure is easily withstood by the sturdy coronary arteries, but the veins are weak and collapse, stopping flow through the whole endocardium. Flow is returned after the heart finishes its beat (during diastole), allowing the blood to drain and the tissue to be perfused.

Sunday, January 19, 2014

Subliminal semicolon

Looking back at my previous post, I discovered that using a semicolon in a sentence about vitamin D resulted in a subliminal message about biochem:

Friday, January 17, 2014

WILTIMS #96: Foundering in biochem

If you would like to keep my attention in class, never preface a statement with the phrase, "For those of you who are interested in the organic chemistry of this reaction..."

TIL: Tangier disease (also known as hypoalphalipoproteinemia) is an extremely rare autosomal recessive genetic disease caused by a defective ABCA transporter. ABCA normally transports cholesterol and phospholipids out of cells for incorporation into high density lipoproteins (HDL or "good cholesterol"). The lack of HDL in the bloodstream increases the risk for coronary artery disease meanwhile the buildup of cholesterol in tissues causes all sorts of problems depending on the tissue.

The disease gets its name (not the eleven syllable one) from Tangier Island in Chesapeake Bay, where the first few patients were discovered. This is an example of the genetics concept called the founder effect whereby an extremely rare trait from a large population is magnified once it is isolated, such as through the colonization of a previously uninhabited island. Tangier Island's first British colonists brought the diseased allele with them and when two of their great great great great great great great grandkids had children in the 1940s, the disease was finally able to rear its head.

Vascular beds can be either arborizing (tree-like) or anastomosing (interconnecting).

Cholesterol is not a precursor to vitamin D; actually they have the same precursor, but are not interconvertible.

WILTIMS #95: GAGs, gags, gags and gags about GAGs, gags and gags.

Today was a solidly good day. Class was marginally interesting and I found a new way to study for biochemistry (which I'll show you when it's further along). I successfully found money for the club for which I am treasurer. I had a blast playing kickball for an hour with the kids at the juvenile detention center down the road. And the tastiest part was that the interviewee that we hosted last night left us a box of chocolate truffles. On nom nom.

One of the topics in biochemistry today was a class of molecules called glycosaminoglycans or GAGs for short. This awkward acronym made it sound like we were constantly discussing bad science jokes ("The GAGs of physiological significance are...") or the specifics of retching ("Remember this is the only GAG that doesn’t have uronic acid.").

TIL: Hyaluronic acid is a GAG that can be administered by injection into joints as a lubricant.

I also learned that there are a bajillion diseases caused by defects in the glycolipid metabolism pathway:

Thursday, January 16, 2014

WILTIMS #94: CMP is dead, long live FCM!

Exhausting morning today. We had our final exam for Community and Preventative Medicine (CPM) at 8am and then three straight hours of very dry lecture.

CPM is a relatively new course at our school, carved out of the Fundamentals of Clinical Medicine (FCM) course a couple years ago to allow for greater emphasis. So now that CPM is done, any CPMish material will simply be covered in FCM as is was in prior years. It's important stuff but kind of obvious at times, so the class seems like busywork compared to the hard sciences that take up the bulk of our time and effort.

TIL: If phosphoethanolamine cytidylyltransferase is deficient, there will be a build up of diacylglycerol, a precursor of triglycerides which can in turn be converted to fatty acids. Can you find these reaction on my handy-dandy biochemical pathways map?

Here, I'll zoom you in a bit:

Tuesday, January 14, 2014

WILTIMS #93: Happily hairless

Today we had our blood pressure and EKG lab in physiology. I volunteered to be our first guinea pig and got the below 12-lead EKG for my trouble! Part of what's confusing about these is that you only use 10 physical leads to find the 12 signals - also called leads. Whereas six of the signal "leads" are straightforward and relate directly to physical leads (V1-V6), the other six (I, II, III, aVL, aVR, and aVF) are calculated from the remaining 4 physical leads. Simple! Also note that the genius who came up with this system used the numbers 1-3 and the roman numerals I-III in the same identifying system.

My EKG showed that my heart's mean electrical axis (MEA) is at 88° (a bit right of normal, but not pathological) and that my PR interval is a little long which is not normal, but again not pathological.

TIL: On average, women have less hypertension and subsequently less heart attacks than men until the onset of menopause, at which point the incidence increases to match that of men of the same age. This effect is due to the presence of estrogen (a vasodilator) in younger women. When estrogen levels decrease during menopause, its blood pressure reducing effects decrease as well.

Crucified people don't die from hunger, thirst, or even blood loss; they actually die of low blood pressure. The extended vertical position of the body eventually causes blood to pool in the legs, resulting in postural hypotension (low blood pressure from standing up) and eventually syncope (loss of consciousness) due to cerebral hypoxia (lack of oxygen in the brain).

70% of the circulating blood volume is contained in veins. About 5-10% is in arteries and another 5% in capillaries. Where the remaining 15-20% is? No idea. In the heart itself maybe? I think someone is supposed to tell us this in a couple days... I'll keep you posted!

WILTIMS #92: Side effects include...

TIL: Orlistat, an over the counter weight loss drug, has nasty side effects. The drug works by blocking an enzyme, pancreatic lipase, that normally breaks down triglycerides (which can't be absorbed by the gut) to individual fatty acids (which can). The problems with this are twofold: lipid soluble vitamins can't be absorbed, leading to deficiencies, and the unabsorbed lipids leave the body as fatty stool. Mmmm fatty stool! Diet and exercise are starting to sound more... palatable.

Though the drug acts through a different mechanism, it actually causes some of the same symptoms as cystic fibrosis. CF is caused by a defective cellular chloride transporter resulting in unusually thick bodily secretions. This seemingly small change leads to a number of problems, one of which being decreased or blocked pancreatic secretions, which include pancreatic lipase (the enzyme targeted by Orlistat).

Saturday, January 11, 2014

WILTIMS #91: Eureka!

Sometimes I think my consciousness is only a tiny sub-process that my brain employes to keep me occupied while it's working. Case and point: Today, we learned how to read electrocardiograms (EKGs*), which I have been taught at least two other times in my academic career, each time grasping just enough information to survive a test but never really understanding.
Ok, I see how the different waves, segments and intervals line up with the heart's contraction cycle... But why are some waves up and others down? Why do you need a dozen leads when one would seem to do the job?
Today, it just clicked. Made perfect sense. Not sure what I was missing before. I feel like my subconscious was just working away on this one, setting up some EKG-understanding brain pathways while I wasn't paying attention, just in case I should ever come across EKGs again. Well, thank you brain! If you wouldn't mind, could you move on to neurology before the spring block? I know you've also seen those topics a few times before, and hey, it's practically an autobiography for you, so it should be pretty easy.

TIL: Cardiac output is limited by venous pressure. In other words, the heart can only pump so much blood at a time. The maximum amount of blood the heart can pump is determined by a number of factors, like the heart rate, preload, etc. but the limiting factor is the pressure in the veins. Each time the heart pumps, it pulls blood out of the venous system and the veins happily empty, but if the heart is moving too much blood too fast, the veins will collapse. A collapsed vein can't provide any more blood for the heart to pump, so the cardiac output plateaus.

If a spinal cord tumor is located in the lower back just below the tail of the main spinal cord, you don't want to make your incision below the lesion because the cerebral spinal fluid (CSF) will drain and move the tumor caudally (toward the butt) by the change in pressure.  If the tumor is connected to the spinal cord proper, it will dangerously stretch the spinal cord, possibly causing damage.

*The "K" in EKG comes from the original Greek wherein "cardio" is spelled "kardio." Some people use the abbreviation ECG to match the modern spelling, but those people are stupid.

Friday, January 10, 2014

WILTIMS #90: The problem of evil

This evening the campus Oncology Interest Group had as a guest speaker our chancellor, an extremely distinguished and well-spoken pediatric radiation oncologist. I personally think he's just collecting titles ...and winning at it. When answering a rather routine question for this area of medicine, "How do you deal with the unavoidably tragic cases in a field with kids and cancer?," the chancellor waxed philosophic about the "problem of evil." This is the very old conundrum relates to the problem of having evil in the world with an all-good, all-knowing, all-powerful deity.

In medicine and especially oncology, we often (admittedly unfairly) justify some of the things that happen to our patients.
Well, the colon cancer patient had a horrible diet; the lung cancer was undoubtedly due to the 2 packs a day for 40 years; and the guy with the throat cancer drank and smoked!
But pediatric cancers are never the fault of the kid. What's more, the child hasn't lived a long life of fun and debauchery, and may never because of our diagnosis.

So how does one deal with this? The non-religious simply say that it's all random, so I might as well help. The fervently religious may claim that there is some grander plan that for some reason required innocent children to die painfully. But the bulk of physicians, like our chancellor, simply stop thinking so hard about it and help as best they can. Even if there is little we can do clinically, we can improve our patients' and their families' lives by being there for them in these difficult times.

Now for something completely different: I present to you: SuperMouse PEPCK-Cmus! This genetically engineered mouse line was created by up-regulating one enzyme, phosphoenolpyruvate carboxykinase, which is important in gluconeogenesis.

That mouse just ran a 5K race. Crazy.

TIL: Aortic stenosis causes heart sounds to change from "lub-dub" to"lub-shhh-dub".

Excessive fructose ingestion is bad because its metabolism is less regulated in the body compared to glucose. Fructose is quickly used to form fructose 6-phosphate, and it will do this without any negative feedback, consuming all of the body's stores of inorganic phosphate. And that has broad, if vague negative effects on energy metabolism.

Thursday, January 9, 2014

WILTIMS #89: Do as I say, not as I do

Man! When we get a good lecturer, it makes such a difference. After literally falling asleep in physiology, we were kept in rapt attention by our Foundations of Clinical Medicine course ...and FCM is rarely a crowd favorite. We had a talk about providing care to adolescents by a pediatrician who specializes in that prickly demographic. He was hilarious, honest and an absolutely captivating speaker.

One interesting point brought up today was how difficult it is to preach certain professional stances when we are inconsistent about them as a society. For example, recently every pediatric and parenting organisation officially condemned all forms of physical discipline - but the vast majority of us were spanked as kids and don't feel strongly on the issue ourselves. Another one that got some chuckles today was how to tell a teenager that smoking pot is bad when it's legal as of January 1st in Colorado (and again, a good slice of the class has partaken... some quite recently)*.

Hopefully, this same line of reasoning will force me to stay vaguely healthy throughout my life, purely out of fear of my own hypocrisy. No promises though.

TIL: If you're younger than 18, you become an emancipated minor if you are pregnant over the age of 13, a parent, married, enlisted in the armed services, or if appointed by court order (à la Macaulay Culkin of Home Alone fame).

HEADSSS is a dumb though important pneumonic for conducting a psychosocial history:
  • Home - Who do you live with? Where? How is you home life? Any big changes?
  • Education/employment - Are you going to school? How are you doing in school? What grade are you in (compared to age)? What do you what to do in life? Do you work? How much?
  • Activities: What do you do in your free time? Sports? Clubs? Scouts? Anything but solitary gaming etc...?
  • Drugs: Do you know anyone who has experience with drugs? Do you? Smoking? Prescriptions?
  • Sex: Have you ever _____? (Be as explicit as you need to be to ensure understanding) Protection? STDs? Do not assume heterosexuality - always use gender neutral terms.
  • Suicide/depression: How do you feel about yourself? Do you ever feel depressed? (If indicated:) Have you ever thought about killing yourself?
  • Safety, violence, abuse: Do you worry about your safety? Have you ever felt threatened at home? At school?
*Not me! The side-effects of one of my old chemotherapy drugs was permanent lung damage. I have been forbidden from smoking anything ever.

Wednesday, January 8, 2014

WILTIMS #88: Little bunny CO2

My biochemistry professor is an interesting guy. Turns out he worked under Krebs and Fisher - as in the Krebs Cycle, the elegant metabolic pathway that underpins all of aerobic respiration. That Krebs. Unrelatedly, this professor has a bunny funny way of denoting CO2 groups:

TIL: Vitamin B5 (Pantothenic acid) is a component of coenzyme A.

The pyruvate dehydrogenase enzyme complex is a beast of a molecular collection - over 60 total copies of 3-5 different enzymes each with its own prosthetic group. Vitamin B1 (thiamine) is a component of one of these prosthetic groups (thiamine pyrophosphate) and its deficiency, typically only in underdeveloped countries or ye olde sailors, causes the condition known as beri-beri.

If you'd like a good excuse not to exercise, McArdle disease might be for you! The disease is caused by a defective muscle enzyme (glycogen phosphorylase) which normally breaks down the energy storage molecule glycogen into usable energy in the form of glucose 6-phosphate. This energy is what your muscles use at the beginning of exercise. Without this energy, people with McArdle disease experience debilitatingly painful cramps when they start any exercise. The tiny silver lining is that they can actually push through the pain and continue exercising fine thanks to the lipid-based energy that kicks in as a "second wind."

Monday, January 6, 2014

WILTIMS #87: Hello again!

Happy New Year! 2013 was a great year for me (yay med school!), especially compared to 2012 (boo cancer!), so here's to 2014 upping the ante!

We hit the ground running (as usual) today and covered most of hemodynamics (the physics of blood circulation) in Physiology and ALL of glycolysis in Biochemistry. It's still amazing that something that took about a week to teach in undergrad was covered in an hour in medical school - and in greater detail.

Perhaps I'm overreacting though. After all, glycolysis consists of only 10 simple steps!

Glucose is phosphorylated by hexokinase to form glucose 6-phosphate (G6P) via the dephosphorylation of adenosine triphosphate (ATP) to adenosine diphosphate (ADP). G6P is then rearranged into fructose 6-phosphate (F6P) by phosphoglucose isomerase. F6P is irreversibly phosphorylated by phosphofructokinase to form fructose 1,6-bisphosphate (F1,6BP) after the consumption of an additional ATP molecule. F1,6BP is then split by aldolase into dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (GADP). DHAP and GADP are interconverted by triosephosphate isomerase, allowing for complete conversion to GADP, which is exclusively consumed in the next step.
-Halfway there!-
Everything in the second half is doubled thanks to the two molecules of GADP that we derived from glucose. Inorganic phosphate (Pi) is added to GADP by glyceraldehyde phosphate dehydrogenase which simultaneously reduces NAD+ to NADH and produces 1,3-bisphosphoglycerate (1,3BPG). Phosphoglycerate kinase transfers one of 1,3BPG's phosphate groups to ADP, producing ATP and 3-phosphoglycerate (3PG). The remaining phosphate is transferred from the C-3 carbon to C-2 by phosphoglycerate mutase, forming 2-phosphoglycerate (2PG). 2PG is dehydrated to phosphoenolpyruvate (PEP) by enolase. Lastly, pyruvate kinase removes the remaining phosphate, forming another molecule of ATP and our final product, pyruvate.

The net reaction for glycolysis is:
glucose + 2 NAD+ + 2 ADP + 2 Pi → 2 pyruvate + 2 NADH + 2 H+ + 2 ATP + 2 H2O

Appologies for taking this opportunity to study at you!

TIL: The body uses ~200 grams of glucose every day. 80% of this is consumed by the brain and blood cells.

Vasodilator medications reduce the pressure in the arterioles (small arteries) of the circulatory system but also result in increased pressure in capillaries and venules (small veins).