Less than perfect: Harrison's Ch. 104 "Disorders of Hemoglobin"

Note: While I attempt to read the 397 chapters of Harrison's Principles of Internal Medicine, I am writing occasional reflections.

Paradoxically, some parts of our body work best when they fail under stress.
-----
An illustrative story from my freshman year of college:

I decided to buy a wheelie chair for my (miniscule) dorm room from a student who lived 1.5 miles away. How could I transport the chair across campus when I didn't have a car?

I didn't feel like wasting an hour walking there and then walking the chair back. Instead, I elected to waste three hours dreaming up and building an alternative. I decided I would tow the chair with my bicycle by running a rope between them. The only rope I could find, though, was an Ethernet cable that was too short. I improvised, tying the cable to my bike rack and then lengthening the contraption by adding some plastic hangers as a kind of towing hitch. A friend grabbed a chair and took it for a test ride (below).

After a few modifications, the setup worked surprisingly well. So long as I didn't decelerate or turn suddenly, the chair trailed the bike by a comfortable four feet.

I bought the wheelie chair and sped it through the streets and paths of campus, dodging parked cars and drawing whistles and shouts of approval from onlookers. Two-thirds of the way through my journey, though, things went wrong. I steered my bike to the left of a bollard, and the chair instead traveled to the bollard's right. I watched helplessly as the line went taut and then snapped, pulverizing the hangers into a shower of plastic shards.

While cleaning up the mess, I realized with a shudder that my originally-intended design (a simple rope connecting chair to bike) could have seriously injured me. The plastic hangers had dissipated the tremendous shock by shattering and by disconnecting my bike from the chair. Had nothing been there to absorb the shock, my bike would have been flipped backwards, throwing me onto the cement headfirst and onto my back. Oddly enough, my design flaw saved me.
-----
A similar phenomenon, of the "useful design flaw," underlies some of the disorders of hemoglobin. Hemoglobin is the critical enzyme in our red blood cells that carries oxygen to our tissues and carries carbon dioxide to our lungs. Hemoglobin disorders such as sickle-cell trait and thalassemia minor are particularly prevalent in areas endemic to malaria, and for good reason. Put simply, in these diseases hemoglobin is either mutated or unevenly manufactured, weakening the red blood cell. These weak blood cells are less hospitable to infection by the parasite (Plasmodium falciparum) that causes the most lethal form of malaria. And so, for those living in areas plagued by malaria, having weak blood cells is adaptive and life-prolonging.

Examples of other helpful design flaws abound in nature. Hepatitis C and HIV replicate their genomes with significantly lower fidelity than do humans. The numerous mutations generated by these replication errors help the viruses elude our immune systems and frustrate our attempts at making a vaccine.

My classmates and I are striving to become physicians who don't make mistakes. Nature, though, doesn't have to set so high of a bar for itself. Sometimes, less than perfect is just right.

Harrison's Ch. 27: "Sleep Disorders"

Note: While I attempt to read the 397 chapters of Harrison's Principles of Internal Medicine, I am writing occasional reflections.  

From Harrison's Ch. 27 ("Sleep Disorders"):

Driving is particularly hazardous for patients with increased sleepiness. Reaction time is equally impaired by 24 h of sleep loss as by a blood alcohol level of 0.10 g/dL. More than half of Americans admit to having fallen asleep while driving. An estimated 250,000 motor vehicle crashes per year are due to drowsy drivers, causing about 20% of all serious crash injuries and deaths....

Failure to recognize and treat [sleep apnea] appropriately may lead to impairment of daytime alertness, increased risk of sleep-related motor vehicle accidents, hypertension and other serious cardiovascular complications, and increased mortality. Sleep apnea is particularly prevalent in overweight men and in the elderly, yet it is estimated to remain undiagnosed in 80–90% of affected individuals. This is unfortunate since effective treatments are available.

Traditionally, doctors and patients haven't given terribly much thought to the health impact of the third or so of our lives we spend in bed. But as we become more overweight (causing sleep problems) and as we better understand the health burden of sleep problems, perhaps there will be a renewed focus on sleep.

When I was seeing patients in a primary-care clinic, I asked some of them whether they felt well-rested during the day. Most said they were sleepy all the time. When I then administered the Epworth Sleepiness Scale, a standard test to assess risk for sleep apnea, some of the results were startling. One patient scored a 21 out of a possible 24, with 9 being the cutoff for urgent referral to a sleep expert. Patients were falling asleep during business meetings and while driving. I dutifully referred them for a home sleep study. I regret not having asked more patients about their sleeping habits, because I'm sure that many of them had undiagnosed sleep apnea. I vividly recall years ago hearing a sleep expert call sleep apnea a "walking time bomb."

I also saw a handful of patients who had been diagnosed with sleep apnea and who were on treatment (typically CPAP, a mask worn at night that supplies air). They said they felt like new people.

---

I recently came across the excellent "Anonymous Doc" blog, written by a medical resident. He writes about a time he was very sleepy.

Harrison's discusses the phenomenon of tired medical residents in the chapter:

Resident physicians constitute another group of workers at risk for accidents and other adverse consequences of lack of sleep and misalignment of the circadian rhythm. Recurrent scheduling of resident physicians to work shifts of 24 h or more consecutive hours impairs psychomotor performance to a degree that is comparable to alcohol intoxication, doubles the risk of attentional failures among intensive care unit interns working at night, and significantly increases the risk of serious medical errors in intensive care units, including a fivefold increase in the risk of serious diagnostic mistakes. Some 20% of hospital interns report making a fatigue-related mistake that injured a patient, and 5% admit making a fatigue-related mistake that results in the death of a patient. Moreover, working for >24 h consecutively increases the risk of percutaneous injuries and more than doubles the risk of motor vehicle crashes on the commute home.

Uh-oh.

Rare

I saw a patient with Menkes Disease, a rare and serious disease in which the body cannot adequately absorb copper from the diet. Most doctors know this disease only as a paragraph in one of their textbooks, or as the subject of twenty seconds of one medical school lecture. Although it is tragic to see a patient with an incurable disease, encountering the flesh-and-blood embodiment of this rare entity felt something like a stroke of luck. I now am among the privileged few to have seen the real thing up close.

'Medicine in Translation: Journeys with My Patients', by Danielle Ofri

In "Medicine in Translation: Journeys with My Patients", Dr. Danielle Ofri retells the remarkable stories of about a dozen of her patients. Dr. Ofri is an attending physician at Bellevue Hospital in New York City, the nation's first public hospital. Dr. Ofri's stories are about moving to a new country: her patients are immigrants who are trying to maintain their identity in the American melting pot. One patient was left horribly disfigured by a politically-motivated attack in his home country. Another needs a heart transplant but cannot obtain one because of her undocumented status. They persevere in the face of tremendous obstacles.

Dr. Ofri tries to bridge the cultural and language barriers that separate her from her patients. She decides to become an immigrant of sorts: she relocates her family to Costa Rica for a year as a break from medicine and as a way of acquainting herself with the culture and language of some of her Hispanic patients.

It is a touching little book. Dr. Ofri cares for her patients and cares about them, too. Her writing captures how she learns from her patients and uses their example to better herself.

Happy anniversary!

From my first blog entry, on August 18, 2011:

Science only gets the doctor so far. We understand the biochemical mechanism of hypertension, we understand how deadly it is, we can easily diagnose it, and we know how to cheaply and effectively treat and even prevent it. Yet hypertension still afflicts a third of adults in the U.S. and kills a substantial fraction of them. We can't escape the fact that patients are people, with people's foibles, strengths, and shortcomings. This makes treating chronic illness frustrating and sometimes ineffectual. But that I am dealing not just with kidneys and arteries and hearts, but with people, is what also makes clinical medicine intensely rewarding.

115 entries and one year later, I mark the anniversary of this blog.

To my surprise, more and more people have been stopping by. Since November, readers from 70 countries have visited. Within the United States, visitors came from 47 states plus the District of Columbia. The blog comes up on the first page of search results when one types "reflex hammer" into Google. The American College of Physicians featured the blog on its website, as a "Notable Voice of Internal Medicine." It has been an electrifying feeling. When I started, I figured the only people who would read my writing would be my family and a few friends.

I'm grateful to readers like you for allowing me to share my story. Thanks very much!

Harrison's Ch. 392: "Alcohol and Alcoholism"

Note: While I attempt to read the 397 chapters of Harrison's Principles of Internal Medicine, I am writing occasional reflections. 

In Lysistrata, by the ancient Greek playwright Euripides, the wives of the warring Athenians and Spartans revolt. The women collectively agree to withhold sexual privileges from their husbands and lovers until the men of the two cities make peace. A peace conference quickly follows. A treaty is successfully negotiated, thanks in part to the hefty amount of alcohol consumed by the ambassadors on both sides:

1ST ATHENIAN
I've never known such a pleasant banquet before,
And what delightful fellows the Spartans are.
When we are warm with wine, how wise we grow.

2ND ATHENIAN
That's only fair, since sober we're such fools:
This is the advice I'd give the Athenians—
See our ambassadors are always drunk.
For when we visit Sparta sober, then
We're on the alert for trickery all the while
So that we miss half of the things they say,
And misinterpret things that were never said,
And then report the muddle back to Athens.
But now we're charmed with each other. They might cap
With the Telamon-catch instead of the Cleitagora,  
     ["they could perform Spartan poetry instead of Athenian poetry"]
And we'd applaud and praise them just the same;
We're not too scrupulous in weighing words.

From even before the time of the Greeks, alcohol consumption has been a part of our literature and a part of our lifestyle. 

---

The time I am spending on the hospital wards is showing me another side of alcohol: the terrible toll that it exacts from some of its consumers. One such patient who was in her twenties had suffered complete liver failure because of heavy alcohol consumption. As such, she was badly jaundiced. The whites of her eyes were now a dark yellow and her fair skin was now a dark green-brown. Her chances of being alive in 3 months' time were under 15%. Another patient had lost the ability to walk or sit up unassisted because of alcohol-induced degeneration of the part of his brain (the cerebellum) that regulates balance. According to Harrison's:

Because 80% of people in Western countries have consumed alcohol, and two-thirds have been drunk in the prior year, the lifetime risk for serious, repetitive alcohol problems is almost 20% for men and 10% for women, regardless of a person's education or income. While low doses of alcohol have some healthful benefits, the intake of more than three standard drinks per day on a regular basis enhances the risk for cancer and vascular disease, and alcohol use disorders decrease the life span by about 10 years.

As much as I enjoy having a beer, I've started to see alcohol as a poison above all else. Although you might think that doctors would know better, Harrison's also points out that "the lifetime risk for alcoholism among physicians is similar to that of the general population."

Alcohol consumption is increasing in the United Kingdom and Russia and is surging in new markets like India and China. As an increasing number of people worldwide try alcohol for the first time, more will abuse alcohol, with the concomitant problems that alcohol wreaks on the body and the mind.

Although treatment for alcohol addiction is in its infancy, doctors are getting a better sense of what interventions are effective. There even are a few medications, such as naltrexone, that seem to blunt cravings. The outsized public health impact of alcohol consumption also means that medical innovations in this field will have an outsized effect on people's well-being.

Going zebra-hunting

The aphorism handed down to medical students like myself goes: "When you hear hoofbeats behind you, don't expect to see a zebra." In medical parlance, "zebras" are rare diseases. Zebras are those obscure diseases that a doctor learns about in medical school and then never encounters again.

Recently I went zebra-hunting on the hospital wards. While the professor showing me around checked on an ill patient with a failing organ, I noticed at the patient's bedside table a large tub of fancy imported licorice. Some of the licorice had already been eaten. I asked the patient if she likes licorice. She responded that she loves the stuff, and eats a substantial amount every day.

What the patient didn't know was that a compound in licorice, glycyrrhizic acid, inhibits an important enzyme found in the adrenal glands. Consuming moderate-to-severe amounts of licorice can cause certain medical problems (like hypertension and fluid retention) that would have been particularly harmful for this patient. I brought this up to the medical team, and they told her to stop eating licorice.

Another patient had episodes of disabling, unremitting headaches that would last for weeks. I suspected hemicrania continua, a rare headache disorder that seemed to fit the case quite nicely.

I had read somewhere that those most likely to diagnose rare diseases are old doctors (because they've seen everything) and those still in training (because they spend a disproportionate amount of their time learning about rare diseases). I am still early in my training. It's not clear to me whether the reason I am finding zebras is because my eye is keen or because I don't know what I'm doing. I'm becoming increasingly confident that it is the former.

---

Housekeeping note: If you follow the blog, I recommend doing so via RSS feed. RSS allows you to follow your favorite blogs without having to visit the websites individually. A brief primer on RSS feeds is available here. 

Piano Sonata No. 16 in C Major, K. 545

In a secluded room on the top floor of our medical school is a piano by a window. I consider this spot my little birds' nest. Although I only remember how to play a handful of songs, every once in a while I dart upstairs and tap out a tune while overlooking the world below.

Recently, a surprise awaited me atop the piano. Someone had left a book of classical sheet music. I quickly set to work on a lovely Mozart piano sonata that I had always wanted to learn (performed by a professional musician in the video below).

 

Some academic pursuits directly involve the act of creation. Art students create sculptures, computer science students write programs, creative writing students compose stories, and doctoral students craft theses.

Medical school, by comparison, does not demand that we create. It demands that we accumulate and regurgitate knowledge, in the hope that it might help us someday assist patients. The fruits of our labors will come years down the line, in nebulous and intangible ways. I recently read an article about the ethics of harvesting the eggs from a brain-dead patient and then using them for in-vitro fertilization. Will it ever make a difference that I spent those 10 minutes reading that article instead of watching TV? It's hard to say. I doubt I'll ever know. When I go to lecture or read a textbook chapter, it's not immediately clear what I am accomplishing, if anything. Our quest for medical knowledge often lacks a human element. Our examinations are entirely multiple-choice. Selecting from one of five given answers precludes individuality, emotion, and expression.

And so, I find my respite in playing the piano. I hit a key, and instantly it sounds. Sometimes my fingers effortlessly flit across the keyboard: it's as though my hands already know how to play the tune, and my brain's job is simply to sit back and enjoy. There is the technical challenge of obeying the sheet music and getting my hands in position for the notes still to come. Then comes the artistic exercise of making the music have feeling. The payoff is gratifyingly fast. Each time I play the sonata, it sounds better. Not only am I creating, but I am creating something beautiful.

Among the less fortunate

I joined a professor as he rounded on patients in the adult hospital wards. As always, the patients we saw on the wards were quite sick, suffering from several chronic diseases with little chance of cure.

Although some patients were in a bad way of their own volition (alcoholism leading to liver failure, smoking leading to lung problems), some were there because of bad fortune. One patient's spine had been injured in a car crash when she was a teenager, paralyzing her legs, limiting movement in her arms, impairing her breathing, and leaving her incontinent of urine. Her impairments left her vulnerable to infection, and a particularly nasty one had landed her in the hospital. Just one car crash had altered her life's trajectory.

Another patient was a nurse with liver failure because of Hepatitis C infection. Although it wasn't clear how she contracted the virus, her exposure probably came from one of the patients she had cared for.

Why were myself and the physician the ones in the white coats and the patients the ones in the beds? In large part, because of chance. It boggles the mind.

Attraction

One evening years ago, I happened to be studying in the law library of one of the most prestigious law schools nationwide. I was dressed nicely. It was getting late, and the library was nearly empty.

Imagine my surprise, then, when an attractive sorority girl in heels and a rather short skirt plunked down next to me and struck up a conversation. She seemed keenly interested in anything I said. After flirting with me for a couple of minutes, she asked what I was reading.

"It's a textbook on evolutionary biology." I said. "It's fascinating stuff!"
"Huh," she replied. "Why is a law student reading about evolution?"
"Oh, I'm not a law student. I'm an undergrad."

Her disappointment was palpable. Moments later, she was gone.

Before plunging back into my textbook, I mused: what would have transpired just then had I actually been a law student?

Now, years later, I am a medical student. Although my status as a second-year medical student carries little cachet, occasionally it affects how a person interacts with me. A few months back, while traveling between clinics, I had to dart into a market while wearing my white coat. The girl working the checkout stand was my age and started chatting me up. She seemed to be taking a deliberately long time to ring up my order. Sometimes when I've rotated in clinics, members of the ancillary staff have pulled me aside. They have asked me a few times how old I am and even whether I'm single. Some mothers have tried to give me their daughters' cell phone numbers.

At some level, it is nice feeling wanted and appreciated. Yet it bothers me that what garners attention usually doesn't seem to be me or my personality, but simply my belonging to the medical profession. I feel like these interactions sometimes don't happen for the right reasons. It makes me more guarded and suspicious of people's intentions. Part of me prefers the anonymity of when I was nothing more than a wide-eyed undergrad.

Our professors warn us to be cognizant of romantic advances, especially in the clinical setting. An otolaryngologist (ear, nose, and throat doctor) recounted to me one of the first patients he saw as an attending physician. An attractive female patient had come in with an ear complaint. During his examination, she loosened her gown, exposing her breasts. He was dismayed and terrified. No chaperone was present and the patient's state of undress could have given the appearance of something unseemly. Interestingly, a psychiatrist advised us that certain personality disorders make patients particularly prone to pushing the boundary between doctor and patient.

I imagine that as I progress towards becoming an attending physician, the effect I've noticed will become more pronounced. Being a physician will make some people more inclined to befriend me, and others less inclined to befriend me. Regardless, it will become increasingly difficult to dissociate my personal identity and my interpersonal relationships from my professional calling. Is this a good thing?

Medical school is dramatically altering the way I think and the way I perceive people. Perhaps it's only fair that it will alter the way some people see me, for better or for worse.