Alimentary School

So, in med school we've been studying the gastrointestinal tract for the past two weeks. As it turns out, that path ultimately leads to one thing: poop. Here are some fun facts about feces:

- Poo is brown because it contains stercobilin, a breakdown product of bilirubin, which is itself a breakdown product of hemoglobin. Hemoglobin is the substance that makes blood red, and bilirubin is the substance that makes people with jaundice turn yellow. The chemical structures of all these molecules contain series of alternating double bonded carbons called conjugated systems, which absorb specific light wavelengths well and thus cause pigmentation. Bilirubin enters the digestive tract through bile, but if the bile duct is obstructed, poo will be white or gray.

- Poo smells bad because of compounds containing sulfur. These are created by bacterial breakdown of proteins containing cysteine and methionine. This is also the reason farts smell bad. The gaseous volume of farts is mostly nitrogen, carbon dioxide, and hydrogen -- nitrogen from swallowed air, and carbon dioxide and hydrogen from bacterial breakdown of carbohydrates. Gut bacteria will only digest carbohydrates that you can't digest yourself, so foods that contain lots of protein and indigestible carbohydrates, e.g. beans, will cause smelly flatulence. The sound of gas moving through your digestive tract, a.k.a. stomach growling, is medically called "borborygmus". High altitude climbers experience copious flatulence, as gas occupies more volume in a low pressure atmosphere.

- The urge to poo comes from distension of the rectum wall. This causes a reflex relaxation of the internal anal sphincter, a muscle you can not consciously control. You keep poo in by flexing your external anal sphincter. If you don't act on the urge to poo, the rectum will eventually contract and push the feces back into the colon.

- The cholera bacteria is deadly because it produces cholera toxin. This toxin begins a reaction cascade that ultimately opens a channel on the surface of intestinal cells, which allows chloride ions and water to flow into the digestive tract. This causes massive amounts of watery diarrhea, which dehydrates the unfortunate host. This channel is mutated in cystic fibrosis, and it is hypothesized that people who are heterozygous for this mutation have some resistance to cholera toxin, explaining the high frequency of this mutation.

Well, that's it. Medicine is alternately the science of the mundane and the disgusting, but I suppose that's why I'm all the more amazed when I find fascination in the humblest things. Back to the books.

The Future of Medicine?

Sorry it's been a while -- but with the musculoskeletal final safely behind me I can turn to RMV again...

One question that occasionally passes through my mind is "What is medicine going to look like 30 years from now?" In my 50's, I'll probably be at about the highest arc of my career, but will that career be recognizable? After all, scientific progress proceeds exponentially -- in the 2040's, the present era will probably seem just as quaint as the 1890's do now. Many older physicians tell me that a great deal of what they learned in medical school is obsolete, a trend that has no sign of fading.

What brought this to mind was an article in Wired magazine (sorry, not online yet) about the Archimedes organization, whose goal is to produce a computer program that can quantitatively model the human body, completely. Quite an ambitious project, considering the untold intricacies of human physiology -- here is a chart that shows JUST the metabolic reactions! If successful, this would be a holy grail for medicine. Every drug's effect could be simulated before touching a human. Combined with genetic information, treatment algorithms could be personalized for each individual. Already, the designers have used their system to predict the outcomes of major randomized drug trials, successfully.

I personally think this was a great thing, but the article was not as positive. Will a computer take over the role of a physician? I doubt it. Physicians have always use tools, tests, and rubrics; this will just be a very powerful one. A human being is still the most adaptable and easily programmable computer we have, and physicians will always be needed to interpret for patients the results their science gives them. The doctor of the future will probably need to know much more about statistics then they are currently asked to -- the spheres of epidemiology, computer science, and individual medicine are rapidly colliding.

Cool Stuff on Them Interwebs

OK, this is a lazy post.

Popular Science's Most Amazing Medical Images.
Some of these are cheesy, others touching, and others very, very cool.

This is pretty cool just from an experimental setup standpoint. I briefly worked in a neuroscience lab where we had mastered how to image clusters of neurons in genetically engineered mice -- every time the neuron was activated, it fluoresced, and we could see local-scale firing patterns. The problem was being able to do this while the mice ran in mazes, etc. We used fiber optics, but they would often either pull the tube out of their heads or push it further in and kill themselves. This solution reminds me of the "locomotion compensator," invented by Ernst Kramer and Peter Heinecke in the 70's to track insect movement. (Can't find the original article but here are articles that cite it.) Insert joke here about "reinventing the sphere."

Politely Stabbing Grandpa

My inner boy scout came out today as I voluntarily gave flu shots at the university's geriatric center. When the organizers were asking around a couple weeks ago, I said yes right away -- because the idea scared me. I've been cutting and chiseling a cadaver for weeks now, but sticking a needle into a live person? Now that's bizarre. Yet by noon today, I had already given about two dozen flu shots.

The shot itself was easy. Sure, I had to be careful not to go too far into the muscle, a little tricky on some the frailer patients. But the needles were so small and sharp, and automatically retractable, that technically there was almost no problem at all. Talking with the elderly, however, was much harder. Some of them were a little grumpy and just wanted to get out of there. Some were happy to be there, but very hard of hearing. More subtly, though, were the little differences in customs and mannerisms. How do the elderly want health providers to dress? What greeting and level of conversation do they expect? What makes them comfortable? I also noticed that some made strange (yet well-meaning) comments about my female and minority colleagues (for example, asking the Chinese student from Detroit if "you're doing this because your culture values your elders.") You could almost compare our interactions to time-travel; I get to navigate the social terrain of 50-odd years ago.

It was a good experience, perhaps because it made me feel more like someone training to be a doctor and less like a molecule memorization machine. Also, it was good as a quick trainer for personal skills. The instructors here constantly emphasize how important they are. As a doctor, someone you have never met before will walk into your room, and within one minute has to feel comfortable getting a needle, or talking about drug use, or showing you their genitals. Failure to build that trust can lead to real medical problems, if people feel too hesitant to share some vital piece of information with you. I've got a lot to learn...

Screened

Like millions of other students around the country, I was required to get a screening test for tuberculosis before starting school this month. I went to the corner family health clinic, got my injection, and came back a couple of days later. Unlike many other students, my test was positive. I couldn’t believe it—my hand was visibly shaking as we discussed the results. Would I be allowed in the school? Would I even be allowed near the other students? The nurse reading the test just laughed and told me not to worry; most medical students have been exposed to TB by their first year in the clinic, so I’ll just have a head start on the class. Just to be sure I didn’t have an active infection, however, she signed me up for a chest X-ray.

You’ve probably had one of these skin tests before. Often called a PPD test for purified protein derivative, the provider injects a droplet of fluid containing tuberculin bacteria proteins between the layers of your skin. When you return two days later, the clinic checks to see the degree of immune response your body has mounted against the foreign material. Usually, the spot is red for a few hours and then fades away: your body does not consider the proteins threatening. But if the spot remains raised, it means your immune system has responded more aggressively and in all likelihood has seen live tuberculosis bacilli before.

The chest X-ray showed no visible lesions in my lungs. For now, the best interpretation was that I had only a latent infection and was not contagious. Still, my lifetime risk of developing active TB was 10% unless I took a long course of anti-tuberculosis medications. “When could this have happened?” I wondered. A moment’s reflection provided some answers: I had spent all of last year working in a large hospital, and I had recently traveled in South East Asia, including some very rural areas. I could have easily been exposed in either of those places without realizing it, carrying a small colony of tuberculosis bacteria in my body unawares.

As a health minded medical student, I decided I must absolutely begin the anti-TB drug Isoniazid as soon as possible. It looked promising—finishing the course would reduce my lifetime risk of active TB from 10% to less than 1%. But the drug was not easy. I would have to take a pill every day for the next nine months. I would have some risk of neuropathy and anemia, but most certainly of liver damage, requiring a long hiatus from my enjoyment of craft beers (unthinkable!).

Still, it was necessary. Before starting the drug, however, they wanted to do one more test to make sure I really had TB, a test with much higher specificity. The “QuantiFERON-TB Gold” test required a small amount of my blood, which they mixed with TB proteins (similar to the ones injected into me earlier). If my white blood cells released lots of interferon (an immune attack signal) in response to the proteins, then I had indeed been exposed to TB.

Fortunately, they didn’t. A single phone call from the clinic made my year—I didn’t have TB! After I finished dancing in my living room, I was left with a list of questions: How could the two tests be different? What if I had taken the drug and had liver damage? Why even give PPD tests at all?

I had my brush with a false-positive, one of the reasons we don’t screen everyone for everything. Something non-intuitive and often surprising is that the accuracy of a test depends just as much on the population it is given to as on the characteristics of the test itself. For example, suppose a test with 99% sensitivity (ability to catch disease carriers) and 99% specificity (ability to identify people without the disease) is given to a population of 10,000 where 100 people have the disease (1% prevalence). Even with such an amazingly good test, only half of the people with a positive result would actually have the disease! This problem will always happen when a screening test is given to a population with a low prevalence. Test results don’t define your chance of having a disease, they adjust your risk based on the chances you came in with. This was very poorly understood by Illinois’ Gov. James Thompson in 1987, who enacted a law requiring HIV testing of all couples applying for a marriage license. Since heterosexual, monogamous couples were probably the lowest risk group besides cloistered clergy, even with a near perfect test there would still be an egregiously high number of false-positives. Indeed, there were, and most couples went out of state to marry until the law was repealed in 1989.

Even when good tests are available, expense is also a consideration. The PPD test is the mass screening test not because it is the most accurate, but because it is the cheapest. Since the main risk in the beginning is missing people who actually have the disease, the guidelines are set up so that nearly everyone who has the disease will have a positive test, plus a few people that don’t have the disease as well (a sensitive test). Only after the initial screening do we use the more expensive and more specific interferon test to knock out those false-positives who definitely don’t have the disease. Interestingly, it’s hard to tell what the actually accuracy of the different TB tests are, since there is no gold-standard (a supposed perfect test) with which to compare them to. A study used cross comparison statistics to try to find an answer, and you’ll see it’s nowhere close to our hypothetical example.

So, should we even continue giving TB screening tests to students, given that they are such a low-risk population in general? Once all the bad results are sorted out, the bottom line is that the TB test is useful because we can do something about the results—effective treatments are available. The clinical utility of a test is even more important than the accuracy when deciding on a screening program. There is a near perfect test available for Huntington’s disease, but 95% of at-risk people choose not to get it, since there is no treatment for the fatal illness. In the middle of all these questions is the debate over prostate cancer screening by PSA, in gray areas both for accuracy and clinical utility. 23andMe will scan my genome for markers associated with heart disease and diabetes, but could I really use the information that my lifetime risk is 9% instead of 7%?