f--- medicine

from today's exam, a surprise question on SIADH--syndrome of inappropriate anti-diuretic hormone. at first glance i did not recognize SIADH, so i turned to my rational, sensible powers of deduction to analyze the syndrome's name. clearly, i thought, SIADH has something to do with abnormal levels of ADH. whether SIADH causes inappropriately high ADH secretion or inappropriately low ADH secretion, however-- well, that's anyone's guess, seeing as "inappropriate" is a SUPREMELY USELESS DESCRIPTION.

as it turns out, SIADH results in excess ADH and hyperconcentrated urine, which in retrospect is mildly suggested by the adjective "inappropriate." but why the medical bigwigs can't just rename it the syndrome of excess anti-diuretic hormone, i haven't a clue. instead, i had to agonize for 5 precious minutes over an ultimately random guess, using approximately zero brain cells in the process. so much for assessing my medical knowledge, my critical thinking skills, my academic aptitude, whatever...

*sigh*

mr. october

"the straw that stirs the drink." reggie jackson, the former yankee slugger, is known for his postseason heroics, in particular his 3-homers-on-3-pitches world series game (i forget which year). he was the prototypical playoff catalyst, and it is in his honor that i write this last-minute entry on key biochemical enzymes.

in glycolysis, there are four irreversible regulated steps:

D-glucose --> glucose-6-phosphate
- glucokinase in liver, hexokinase everywhere else

fructose-6-phosphate --> fructose-1,6-bisphosphate
- phosphofructokinase (rate-limiting step)
- inhibited by ATP, citrate
- stimulated by AMP, fructose-2,6-bisphosphate

phosphoenolpyruvate --> pyruvate
- pyruvate kinase
- inhibited by ATP, alanine
- stimulated by fructose-1,6-bisphosphate

pyruvate --> acetyl-CoA
- pyruvate dehydrogenase complex
- inhibited by ATP, NADH, acetyl-CoA

the common theme regarding glycolytic enzyme regulation is that high energy molecules or molecules produced by high energy processes inhibit glycolysis, i.e. telling the glycolytic pathway that it no longer needs to metabolize glucose to make energy.

in the citric acid cycle, here are the key regulated enzymes:

citrate synthase
- inhibited by ATP

isocitrate dehydrogenase
- rate-limiting step
- inhibited by ATP, NADH
- promoted by ADP

alpha-ketoglutarate dehydrogenase
- inhibited by succinyl-CoA, ATP, NADH

like glycolysis, the TCA cycle is slowed by those molecules signalling adequate energetic fuel.

bah. i'm pretty sure a lot of what i just wrote is incorrect. sleepy time.

final countdown (1:48)

pretend you're barry bonds. in addition to the lingering destructive effects of all the 'roids you may or may not have been taking, when you press your hands against a wall to do a basic calf stretch, you notice that your left shoulder blade is sticking out unusually far. you notice it because it's stretching out the under armour heatgear workout shirt you're wearing, and you also feel moderate pain in your left shoulder. as a result, you have to do extra rehab for your injured shoulder, and in doing so you erase any chance of albert's fantasy baseball team making a late summer comeback.

this is injury is known as a winged scapula. it's typically the result of damage to the long thoracic nerve, which ennervates the serratus anterior muscle, which attaches to the scapula (shoulder blade). the resulting paralysis limits the motion of the scapula, causing it to bulge out the back.

---

tomorrow, it's go time.
 

the bane, part two

i know i promised to write something more metaphor-friendly this time around, but i lied. immunology continues to run circles around me, and i need to fight back. what i will do, though, is (try to) place this otherwise intrinsically meaningless discussion of lymphocytes in the context of HIV/AIDS. even if the letters and numbers are still greek to me, at least they'll seem at least collectively more significant in the setting of a truly frightening disease. on that cheery note, here's my basic understanding of lymphocytes, aka T cells and B cells:

in high school health class, you probably learned something about how HIV and AIDS work. the virus kills "helper" T cells, which are part of the body's natural defense system, and the debilitated victim eventually dies from an infection. along with B cells (bone marrow-derived), T cells (thymus-derived) are lymphocytes, specialized cells that are responsible for adaptive immunity--the body's specific response to (presumably) foreign invaders. although functionally distinct, B cells and T cells communicate extensively, signalling one another with dozens of molecules in countless scenarios.

"helper" T cells are called helpers because they don't do any killing--they just signal. appropriately, cytotoxic "killer" T cells do a fair share of the killing. in other words, helper T cells are pussies, albeit clever, essential ones. moreover, helper T cells are further classified into two groups: Th1 and Th2. respectively, two signaling molecules induce the development of a baby (naive) helper T cell into these two distinct types: interleukin-12 (IL-12) and IL-4. the best way for me to remember that IL-12 induces Th1 development is that both IL-12 and Th1 have the number "1" in their names. incidentally, this is one of the prime examples of why immunology makes me want to light myself on fire.

but i digress. Th1 is a key player in cell-mediated immunity, the principle mechanism through which the body defends against viruses and certain bacteria. IL-12 essentially gives helper T cells a heads up that a virus or bacterium is wreaking havoc somewhere, and in turn the activated Th1 cell releases two signaling molecules--IFN-gamma and IL-2--to activate and direct killer cells. IFN-gamma activates macrophages, and IL-2 activates killer T cells. as far as i can tell, the "cell" in "cell-mediated" refers to these killer cells. maybe i'm wrong. boo freaking hoo if i am.

on the other hand, Th2 cells, via IL-4 activation, anchor the antibody-mediated immune process. you can't spell antibody without the letter "b," and so it follows that B cells produce antibodies and are the targets of Th2 signals. again, this is why i hate immunology. most of my classmates, if they see "antibody," they automatically think "B cell." for me, when i see "antibody," i think, "shouldn't it be written 'anti-body'? and why didn't they call it "contra-body" instead? that way, a molecule called ABAB would carry some intrinsic value." it's all i can do not to write "anti-body" in my notes. but again i digress. Th2 cells produce and send out IL-4 and IL-5 molecules to help B cells make antibodies, which then control particular extracellular pathogens.

this brings us back to HIV. HIV does in fact destroy helper T cells, but which ones: Th1 or Th2? i had to google this question for an answer, and even then i couldn't find anything definitive. it appears HIV preferentially invades Th1 cells, but Th1 cells are better at controlling the internalized virus, whereas Th2 cells are less often infected but are weaker upon infection. a third possibility is that HIV infects naive T cells (Th0), but i recently read an abstract arguing against this idea. still, between the two of them, Th1 and Th2 cover the body's chief defense mechanisms against infection, which is why HIV's destruction of both helper T cell-types is so devastating.

deez nutz

one of my glaring weaknesses as a medical student (and as a person, really) is my pride. there are certain student-ish things i have historically refused to do--reread my notes, use a highlighter, write flash cards, etc. in the course of the past year, however, i've humbly had to break every one of these personal rules in order to manage the sheer bulk of material we have to learn. every rule, that is, except one: the no flash cards rule.

i should qualify this statement first and admit that i have cut 200 blank cards and have even written up two cards--one for choleragen and one for hereditary angioneurotic edema. to this day, those two cards remain unflipped, and therefore i don't count them as flash cards, i.e. they haven't been flashed.

still, as a result, i have abstained from flash card usage all year, often to my detriment. and in no instance was this detriment more obvious than when i was studying immunology. immunology became the bane of my existence because of its insistence on using nonsensical letters and numbers to describe everything that happens within it. the classic, most glaring example of this is the collection of cell surface molecules called CD molecules. even the deceptively simple "CD" name already presents a baffling challenge. call up a med student friend and ask her or him what "CD" stands for, and i bet you my tuition that your friend won't know (answer: clusters of differentiation, which, of course, is no more helpful than CD).

moreover, there are well over 200 of these CD molecules, approximately 1/6 of which we're expected to know, and none of which have useful, descriptive names, unless you naturally think "CD16" screams "phagocytosis." any normal student faced with the task of memorizing 40 CD molecules and their respective functions would head straight to a pile of blank flash cards or think of yet another corny mnemonic to sort everything out. unfortunately, i have neither the discipline nor the cleverness to do either, and so i'm simply going to list the relevant CD molecules below. next entry i promise to use more metaphors.

T-cell markers (CD2-8):

CD2
CD3 - part of the signal transducing complex that associates with the alpha/beta T-cell receptor (TCR, which cannot signal on its own)
CD4 - the receptor for class II major histocompatibility complexes (MHC). CD4 possesses no signal transducing function.
CD5
CD7
CD8 - the receptor for class I MHC. CD8 also does not possess any signal transducing function.

CD28 - provides a critical second signal for activation of T-cells. if the antigen presenting cells do not express the appropriate counter-ligand (CD80 or CD86), T-cells may be anergized (rendered "blind").

myeloid lineage markers (CD11-18):

CD11b
CD13 ]
CD15 ]--- elevated levels of these indicate myeloid leukemia
CD33 ]

B-cell markers (CD19-low 20's):

CD19 - deficiency in CD19 indicates agammaglobulinemia (e.g. low IgG)
CD20
CD21 - also found on follicular dendritic cells
CD22
CD23

CD10 - aka CALLA (common acute lymphoblastic leukemia antigen), CD10 is found on pre B-cells and hence indicates acute B-cell leukemia when detected in high levels. functionally, CD10 is a protease that helps immature B-cells navigate through the extracellular matrix.
CD40 - provides a critical second signal for activation of B-cells, in particular for immunoglobulin class-switching (IgM --> IgE) and for affinity maturation.

natural killer-cell markers:

CD2
CD7
CD8 - expressed at much lower levels than in cytotoxic T-cells
CD16
CD56

monocyte markers:

CD4
CD13
CD14

miscellaneous CDs:

CD32 - neutrophils, monocytes/macrophages, B-cells
CD34 - blasts
CD45 - all white blood cells
(CD45RO - memOry cells)
(CD45RA - nAive cells)
CD64 - monocytes/macrophages

breathe, stretch, shake

the reason we inhale is to acquire oxygen to fuel our cells, and the reason we exhale is to expel the carbon dioxide that our cells have byproduced. in particular, carbon dioxide (CO2) is a curious gas--found in trace amounts in the air, it's often maligned as a greenhouse gas but is otherwise fairly harmless. dissolved in water, however, CO2 becomes an acid, which is why plain seltzer water tastes mildly sour. this is partially why CO2 must constantly be pumped out of our cells and our blood, so that our bodies' systemic pH does not get so low as to become harmful to normal cellular function.

let's say that, for some unfortunate reason, your lung function has suddenly diminished, and you can't breathe as quickly or as strongly as you normally should. this is hypoventilation. as a result, carbon dioxide is backing up in your blood, and this is lowering your blood's pH (i.e. making it more acidic). how does your body compensate for low blood pH? it has two options: 1) eliminate the CO2 via the lungs, which it currently can't, or 2) neutralize the acid. option two is where your kidneys come in (and where a few of my comp exam questions are sure to attack).

in the event of respiratory acidosis--like the case just described--the kidneys provide a buffer to ameliorate the downward swing in pH: bicarbonate. bicarb is the same compound found in baking soda and antacids, and its action in all uses is similar--to neutralize acid. the kidneys know to produce bicarb because they can sense both the increase in dissolved arterial CO2 and the lowered pH of arterial blood (the kidneys also pump out and excrete acidic hydrogen ions). dissolved bicarbonate equilibrates with the hydrogen ions in solution freed by CO2, and normal pH is restored.

now, let's say that your lungs are working fine again, but for an unrelated yet still unfortunate reason, you decide to shoot vinegar into one of your veins. as this example shows, not all acidoses are caused by pulmonary insufficiency. lung function--and corresponding amount of dissolved CO2--may be perfectly normal when another type of acidosis sets in. this is termed metabolic acidosis, and the body's compensatory response in this situation is slightly different.

in metabolic acidosis, the kidneys still secrete extra bicarbonate to neutralize acidic blood. however, the amount of arterial CO2 in metabolic acidotic patients is below normal. this seems counterintuitive because raised--not lowered--arterial CO2 levels stimuate the kidney cells to excrete hydrogen ions, as described in the respiratory acidosis case. however, because the lungs are functional in this case, they attempt to correct the acidosis by hyperventilating (i know the causation here is muddled but just bear with me), resulting in the decreased dissolved CO2. this, in turn, means that less bicarb is ultimately needed to neutralize blood acid.

all this serves to answer the following prototypical "renal regulation of hydrogen ion balance" test question:

if a patient presents with an extracellular pH of 7.32, an arterial CO2 pressure of 60 mmHg, and an arterial bicarbonate concentration of 30 mEq/L, what type of acid-base disorder does he have?

answer: respiratory acidosis

likewise, if a patient presents with an extracellular pH of 7.21, a pCO2 of 25 mmHg, and a bicarb of 10 mEq/L, what type of acid-base disorder does he have?

answer: metabolic acidosis

(normal values approximately are: pH=7.4, pCO2=40, [HCO3-]=24)

c is for cookie

in 9th grade, my math teacher wrote on the blackboard one of those cute classroom proverbs that makes teachers seem so wise. this one was a list--maybe 10 items long, i don't remember--of increasingly effective ways of learning. the least effective was reading from a book. the most effective was teaching another person. i grew to despise that math teacher, whom to this day i believe had it out for me and deliberately issued me a poor grade on my final exam, refusing to allow me--or my parents--to see the test. it was my first and last B in high school. needless to say, i'm over it.

but as for her top ten list of best learning methods, i think she was right. it's five days before my end-of-year comprehensive exam, i.e. five days before my first year of medical school is over. i don't necessarily have to pass in order to move on to next year, but i'd like to finish the year on a respectable note. for the past couple days i've sifted through my review books, highlighter in hand, carefully reading every previously-marked page. at this point though, the diminishing marginal utility of every page i read is depressing, and so in these increasingly desperate times i'm looking for a quick, high-yield method of retaining what i'm reading.

enter this shiny new blog. seeing as my primary blog continues to hum along nicely, and as it remains one of the best ways to keep in touch with many of my best friends, i've had trouble justifying this blog's existence. but i think i have a solution (albeit a dry, selfish, nerdy one). every day, starting today, i will post something i have learned in school. it might be a factoid presented to us in class, a summary of a journal article i skimmed in the afternoon, or a difficult concept i can't seem to untangle. whatever it is, i'm fairly sure i'll understand it better just by trying to write it clearly and palatably. and for you, well, maybe you'll find these daily doses of my medical education interesting. if not, i can hardly blame you.

so here's my contribution for the day:

do you remember the sesame street skits with cookie monster and the x-ray machine? cookie monster would step behind the x-ray screen, eat his cookie (100% of which would spray out of his mouth, but that's beside the point), and everyone would watch his cookie bolus make its way down his digestive tract. it was my introduction to gastrointestinal physiology, and i loved it.

so let's say you eat a cookie. after you've chewed it thoroughly and swallowed, the erstwhile cookie slithers down your esophagus, passes through the digestive pearly gates--the lower esophageal sphincter--and settles onto the hot, acid inner surface of your stomach. incidentally, your stomach knew the cookie was coming and made the appropriate preparations to receive it. it's in a relaxed state, thanks to the vasovagal reflex, and therefore ready to be filled. vagal nerve fibers released vasoactive intestinal peptide (VIP) onto myenteric motoneurons to reduce the resting tone of the stomach smooth muscle. also, before you even bit into the cookie, the G cells of your lower stomach (the antrum) released the digestive hormone gastrin into your bloodstream, thereby stimulating the secretion of hydrochloric acid by parietal cells and priming your stomach milieu for the now-famous cookie.

i mentioned the antrum portion of the stomach. the stomach is divided into roughly three sections--the fundus (top), the corpus (middle), and the antrum (bottom). gastric contractions, signaled by gastrin, start in the mid-corpus and increase in force towards the antrum. this asymmetric distribution of motor force results in the characteristic churning motion of the stomach, termed retropulsion. retropulsion pushes antral contents back towards the fundus, where the soupy stomach mixture hits the upper stomach wall and slides down towards the antrum, only to get pushed up again in the next contractile wave. these waves are slow, at roughly 3 per minute, which is why you don't feel your stomach pulsing after you eat. this continues until your cookie resembles putrid orange juice, and this is also where our story ends for today.

p.s. if you spot any mistakes--and there will be plenty i'm sure--please let me know, thanks.

hello

google changed my life, and so i feel i owe it to them to jump ship from xanga one of these days. this blog will be my life preserver.