Tuesday, April 29, 2008

Final 4

No, it's not the last four teams in the NCAA basketball championship. It's the last 4 weeks of school! I had a pharm exam on friday and a path exam on saturday. Both went well, the grades are already back, surprisingly. I did quite well on path which was a pleasant surprise since I had studied pharm far more. I'm going to have to bust my butt on the next exam to do as well as I'd like to in pharm. So far, I think that I can say that medical school isn't too bad. I study a lot, last week put in about 60 hours before the exam, but overall, it's not bad. I can't believe that in a few weeks I can consider myself an MSII. I don't have much else to write. Mindy and I are finding out in two weeks if we're going to have a Dayshawn or a LaFonda.

Tuesday, April 15, 2008

To potentiate or to antagonize, that is the question

A few things are new: first, we are getting a new bed. The current bed has gotten so bad that I spent last night on the floor in a sleeping bag. I would liken it to sleeping in a ladle. Your spine is bent laterally along its longitudinal axis, and also the anterior/posterior axis. If you lie on your back, your sacrum slowly drifts down so you have a nice anteriorly rotated pelvis. This, combined with my year old running shoes means that I live with constant back pain. Having slept a grand total of 5 (ish) hours Sunday evening, I said enough's enough, and moved to the floor where I slept soundly all last night.

To rectify this crappiness, Mindy and I bought a new mattress today. Hopefully this one will last through residency. I have been sleeping like the happy fellow above, and I'm tired of it.

On a more medical note, path and pharm are a lethal combination. There's just so much testable material! We're covering ANS (autonomic nervous system) agents right now, which will be useful if I go into anesthesia. This week we covered muscarinic agonists, antagonists, and acetylcholinesterase inhibitors. We're also covering the α and β agonists, antagonists, and re-uptake inhibitors. Perhaps a brief exposition will clarify and edify:

The ANS is divided into two main branches that govern all of our subconcious bodily functions, including sweating, heart rate, vascular tone, digestive secretions, eye focusing, dilating and contraction, and to some extent the reproductive organs, as well as many others. These two branches are respectively, the sympathetic, and the parasympathetic. These are mainly anatomical terms, referring primarily to the site of origin for the respective nerves. The parasympathetic nervous system is mostly in charge of the "rest and digest" functions, e.g. secreting gastric juices, slowing heart rate, contracting the pupil, constricting bronchiolar smooth muscle (sound familiar all you asthmatics?). The sympathetic nervous system, on the other hand, is in charge of the "fight or flight" response that you associate with fright or stress. This means it increases heart rate, dilates the pupil, dilates the bronchioles, constricts the peripheral vasculature to raise blood pressure, reduces gastric motility, reduces gastric secretions, etc. Still with me? Good.

The two systems also differ in the neurotransmitter secreted at the synapse or junction. The sympathetics release norepinephrine (mostly) and the parasympathetics release acetylcholine. What about adrenaline (which is epinephrine in the US)? It is mainly released by sympathetic stimulation of the adrenal medulla, a wee gland perched on your kidney. These chemicals elicit the effects described previously.

Once the transmitter has been released, it acts on a receptor, which is a molecule that protrudes from the cell membrane. When the transmitter binds the receptor, the receptor modifies other molecules inside the cell and elicits the appropriate response (e.g. secretion or contraction of muscle). Sympathetic drugs stimulate α and β receptors, while parasympathetic drugs stimulate muscarinic and nicotinic receptors (it's a little more complex, but this will suffice).

The real fun begins when you consider the multiple ways to antagonize or potentiate the effects of endogenous neurotransmitters. You can irreversibly inhibit a receptor which means you chemically modify it so it no longer recognizes acetylcholine or norepi. You can competitively inhibit it which means that Ach (acetylcholine) or NE (norepi) have to fight for a spot to bind with the drug. These facts are pretty straight forward though, in comparison with the real meat of the course

When it gets really interesting is when you start considering multiple drugs. What happens to heart rate and blood pressure if you agonize muscarinic receptors, while simultaneously blocking alpha receptors? What's going to happen in the GI if you do this? is the patient going to crap themselves because you overstimulated the parasympathetics?

Ahh fun.

Answer: (as I can figure it out): muscaranic agonization: slow HR due to Ach on M receptor. Increased GI motility. Alpha block prevents baroreflex from stimulating α1 vasoconstriction, so BP stays lower than normal. Also decreases sympathetic tone in GI, allowing paras to dominate. Not sure when you would want the patient hypotensive and bradycardic, but there you have it. Wow. look ma! I larned something!

Sunday, April 06, 2008

Slogging along a Path(ology)

(left: Arachidonic acid molecule)

The title is something of a misnomer. Pathology is actually a great class. It uses thing from pharm, micro, and cell bio. This means that I have to dredge up memories from cell bio of things I haven't seen in maybe 6 months. Path is, to use the current pedagogical buzzword, "integrative." We have lecture only once a week, and then gross lab for 90 minutes once a week, and another small group activity for another 90 minutes. This small group activity is far superior to the organized dawdling that was genetics PBL. First, these groups are self-selected, so I only work with people I know work hard. Second, there is not moderator to dampen any collaboration. The moderators in genetics, just by being present and having control of our grades were likely, even without any effort or outward expression, to quell a lot of the error prone dialogue which makes this kind of exercise educational. The absence of a moderator permits us to explore freely and make mistakes, but also to learn faster because we can be wrong and learn from it. The book is a ponderous compendium, but nevertheless a great resource.

In other news, it looks like my summer research project is going to be funded. Do I fully know what I'm going to be doing? hmmm not really. At least they'll pay me to do it though. This week I learned how (sort of) to do a protein assay. The project I'm currently working on is comparing the lipid content of mouse livers from a high fructose corn syrup (HFCS) and trans fat (TF) diet, vs. control of normal chow. In quantifying the lipids, we quantify them relative to themselves, i.e. what percentage of the fatty acids are arachidonic acid for instance. We also quantify them absolutely by comparing them to the protein content of the liver. Since fatty livers have varying amounts of water, using a dry weight/ wet weight comparison is not as accurate as simply using the absolute amount of protein present which is more or less invariate.

To do this, we extract the protein from the protein layer of a liver homogenate. The liver homogenate is basically ground up liver in a solvent, which is then centrifuged. Different cellular components sediment to different layers, which we can remove by pipette. The protein layer is removed and put into an aliquot. We put a known amount of protein into de-ionized water and run it on a spectroscope. The spectroscope bounces light off the protein, and quantifies the amount reflected. This number then is to give an amount of protein present in the sample that can then be compared with the lipid content. Still with me? basically, the process I just described is what I learned to do last week. I don't know that I could do it again by myself, but I would make a valiant stab at it.