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.
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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.
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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.

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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.

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. 

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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.

Harrison's Ch. 97: "Gynecologic Malignancies"

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

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Cervical cancer is not so scary to Americans anymore because of the Pap smear. Pap smears are good at detecting pre-cancerous cervical cells, and over the past 50 years its widespread adoption has dramatically reduced cervical cancer diagnoses and deaths in the developed world. Unlike most cancers, cervical cancer is usually caused by a viral infection. Certain strains of the human papilloma virus (HPV) predispose cervical cells they infect to malignancy. Now that vaccination against some of these HPV strains is available in the U.S., we can expect the cervical cancer rate to drop even further. It is a triumph of preventive medicine.

These triumphs have barely helped the developing world, though. One of the most preventable forms of cancer still kills surprisingly many.

A handful of researchers are trying to help. Doctors in the U.S. sometimes apply vinegar (acetic acid) to the cervix so that they can visualize cervical cancer cells with the naked eye. The acid turns the cancer cells white. It seems that vinegar could be similarly used in the developing world as a low-cost replacement for the Pap smear. If the health worker sees white lesions, he can freeze them off with a simple metal rod cooled by liquid carbon dioxide.

I think it's incumbent upon us to translate our high-tech scientific advances into low-tech tools that can benefit all.

Harrison's Ch. 148: "Pertussis and Other Bordetella Infections"

While I read the 397 chapters of Harrison's Principles of Internal Medicine, I am writing reflections.

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From Chapter 148:

Pertussis is an acute infection of the respiratory tract caused by Bordetella pertussis. The name pertussis means "violent cough," which aptly describes the most consistent and prominent feature of the illness. The inspiratory sound made at the end of an episode of paroxysmal coughing gives rise to the common name for the illness, "whooping cough."...The Chinese name for pertussis is "the 100-day cough," which accurately describes the clinical course of the illness.

In two weeks, I examined two patients who I was rather certain had pertussis. They had recently begun having coughing fits lasting several minutes. Their lungs sounded clear, and neither was feverish. The fits were so severe that it kept them up at night, and sometimes the force of the coughing fits made them vomit. This last feature, known as post-tussive emesis (literally, vomiting after coughing), is a trademark of pertussis. Whooping cough wasn't a perfect fit--both patients had been vaccinated against pertussis, and neither could recall being exposed to someone with the illness. But nothing else seemed to fit very well, either

We obtained a nasal swab from both patients and sent it to the lab. Both times, the test came back negative! This was quite aggravating. Did I go wrong somewhere?

It's important to note that no test is perfect. This particular test for pertussis has a 90% sensitivity, meaning that only 90% patients with pertussis would have a positive result. Still, this means that the likelihood of two patients having pertussis both getting negative test results is only 1%.

Maybe the specimens weren't collected properly? I reviewed the CDC's guidelines. I hadn't left the swab in one patient's nose for as long as recommended. The swabs weren't refrigerated during transport, which could have potentially caused problems. But even these potential missteps don't seem like they would change the tests' outcome by much.

So was it pertussis? Was it another disease that I didn't think of? Were my textbooks wrong?

These are not just philosophical questions. When a patient has pertussis, not only are they given heavy-duty antibiotics, but so is everyone living in their household. The antibiotics have side effects and can breed resistance. Proper treatment here requires knowing the probability that a patient has the disease.

Medicine is full of ambiguities. I don't know what my patients had, and therefore, I don't know whether the treatment helped them or made things worse. In most cases, I have to learn to be OK with that.

Harrison's Ch. 80: "Involuntary Weight Loss"

Perhaps you watched the film "Julie and Julia" a few years ago. It is partly about a blogger, Julie Powell, who spent a year making every recipe in Julia Child's best-known cookbook.

I am doing something similar (albeit less tasty and less likely to be made into a feature film starring Meryl Streep). I am in the process of reading Harrison's Principles of Internal Medicine in its entirety. Harrison's is a dense, 3,600-page, two-volume tome that is the closest thing to a bible in clinical medicine. I am reflecting upon some of its chapters during the year or so it takes me to finish. 

From Ch. 80 ("Involuntary Weight Loss"): 

Involuntary weight loss (IWL) is frequently insidious and can have important implications, often serving as a harbinger of serious underlying disease. Clinically important weight loss is defined as the loss of 10 pounds (4.5 kg) or >5% of one's body weight over a period of 6–12 months. IWL is encountered in up to 8% of all adult outpatients and 27% of frail persons age 65 years and older. There is no identifiable cause in up to one-quarter of patients despite extensive investigation....Weight loss in older persons is associated with a variety of deleterious effects, including hip fracture, pressure ulcers, impaired immune function, decreased functional status, and death. Not surprisingly, significant weight loss is associated with increased mortality, which can range from 9% to as high as 38% within 1 to 2.5 years in the absence of clinical awareness and attention.

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The patient seemed healthy enough. In her 60s, she had stopped smoking 10 years ago and loved doing aerobics. She was getting over a cold. Although she was being treated for hypertension, her blood pressure now was substantially below 120/80 (i.e. her blood pressure was not high).

The doctor asked her how she had managed to get her blood pressure so dramatically in check. "I've lost a lot of weight," she beamed. "I used to be overweight, but now I've really slimmed down."

"How did you manage that?"

"I dunno. Recently I haven't had much of an appetite." The doctor and I looked at the chart, and the woman had lost about 20% of her body weight over the past year. She had been slightly overweight before and her weight now was the low end of normal.

Upon seeing the numbers the doctor and I shuddered almost imperceptibly. While the patient thought her weight loss was good news, we felt the opposite. We now had to order a variety of lab tests and a chest X-ray, checking in particular for cancer. The doctor cautioned that if this initial battery of tests came back clean, he would have to order yet another panel of tests and imaging studies.

Lots of things can cause weight loss in the elderly, some of them deadly and some of them not. How hard should we be looking for the underlying cause? If we ordered every medical test known to man, we still might not have a clue of what was causing the weight loss.

Part of the art of medicine is deciding how far to pursue leads. How long should a doctor take the patient's history? How many tests should we order? How extensive should a surgery be? There are no clear answers, and part of the burden and challenge of being a medical provider is that it falls to them to make these impossible judgment calls.

Harrison's Ch. 251: "Approach to the Patient with Disease of the Respiratory System"

Perhaps you watched the film "Julie and Julia" a few years ago. It is partly about a blogger, Julie Powell, who spent a year making every recipe in Julia Child's best-known cookbook.

I am doing something similar (albeit less tasty and less likely to be made into a feature film starring Meryl Streep). I am in the process of reading Harrison's Principles of Internal Medicine in its entirety. Harrison's is a dense, 3,600-page, two-volume tome that is the closest thing to a bible in clinical medicine. I am reflecting upon some of its chapters during the year or so it takes me to finish. 

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Although I should have been asleep, last night I was determined to get through another chapter of Harrison's. On a whim, I read "Approach to the Patient with Disease of the Respiratory System." The chapter describes the mechanisms of certain respiratory illnesses and instructs the doctor in how to use physical examination techniques and diagnostic tests to inform his diagnosis.

In a stroke of good fortune, today I evaluated a patient with a nasty cough that began a week ago. It hurt when she breathed deeply. I suspected pneumonia and pleuritis (inflammation of the outer surface of the lung).

I took a lengthy history, and posed some questions that must the patient must have found strange. I asked for a domestic travel history, to rule out the endemic mycoses (three pneumonia-causing fungi found only in particular parts of the country). I asked for her history of international travel, to rule out tuberculosis. I asked if she had pets, to rule out psittacosis (a pneumonia-causing bacterium transmitted from birds).

Then I performed my physical examination, paying particular attention to the lungs. My leading diagnosis became even more specific: a bacterial pneumonia of the left lower lobe of the lung, with pleuritis. My calling which lobe of the lung was affected is a bit like a billiards player calling the pocket where he's going to send the 8-ball. My confidence stemmed partly from my having read the relevant section in Harrison's the night before.

We took a chest X-ray, and sure enough, my diagnosis was on the money.

It was a proud moment because it was a big milestone. I've seen many patients, and I've suggested many diagnoses, but never before have I been able to learn whether my diagnosis was ultimately correct. The number of diseases I'm familiar with grows by the day. My hunches are becoming more accurate, and I'm asking patients the right questions more often.

It's fun to compare how I feel about my skill level now to what I wrote just four months ago. Although I still am far from being a doctor, I'm definitely getting the hang of this.

Harrison's Ch. 1: "The Practice of Medicine"

Perhaps you watched the film "Julie and Julia" a few years ago. It is partly about a blogger, Julie Powell, who spent a year making every recipe in Julia Child's best-known cookbook.

I am doing something similar (albeit less tasty and less likely to be made into a feature film that stars Meryl Streep). I am in the process of reading Harrison's Principles of Internal Medicine in its entirety. Harrison's is a dense, 3,600-page, two-volume tome that is the closest thing to a bible in clinical medicine. I am reflecting upon some of its chapters during the year or so it takes me to finish. 

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From Ch. 1 ("The Practice of Medicine"): 

The Physician as Perpetual Student

It becomes all too apparent from the time doctors graduate from medical school that as physicians their lot is that of the "perpetual student" and the mosaic of their knowledge and experiences is eternally unfinished. This concept can be at the same time exhilarating and anxiety-provoking. It is exhilarating because doctors will continue to expand knowledge that can be applied to their patients; it is anxiety-provoking because doctors realize that they will never know as much as they want or need to know. At best, doctors will translate this latter feeling into energy to continue to improve themselves and realize their potential as physicians...

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I felt tremendously relieved when I recently finished my last exam of the first year of medical school. The relief was not just at being finished with exams, but at finally being able to study the parts of medicine that interest me without having to worry whether it is distracting me from my coursework. Even though I had just begun break, within a few hours of finishing my exams I was back in the library, reading textbooks. I'm not sure whether it's because I find my studies relaxing or whether I've simply forgotten how to relax.

In recent months I've solidified my foundational knowledge enough that I'm now able to learn about complex diseases. I understand the fundamentals of pharmacology, anatomy, biochemistry, histology, and physiology. I comprehend more of the medical terms I come across and can make some sense of blood tests and X-rays. Now that I have the tools, I now feel an unrelenting urge to tackle the massive compendium of knowledge I will need in order to recognize diseases and effectively treat them. In under a year I'll be on the wards seeing patients! I feel way behind, that there's no time to lose.

But of course, I can never be done. There is always more to learn. And we constantly have to refresh our knowledge: some things we learned in our classes just weeks ago have already gone out of date. Beyond that, physicians can always improve the way they interact with their colleagues and with patients.

Going into med school, I didn't expect learning about medicine to be quite this engrossing. I'm surprised at how willingly I've devoted my free time to improving my craft, to the exclusion of other pursuits. Being a "perpetual student" is an enormous obligation.

An ambitious attempt

No greater opportunity, responsibility, or obligation can fall to the lot of a human being than to become a physician. In the care of the suffering, [the physician] needs technical skill, scientific knowledge, and human understanding.... Tact, sympathy, and understanding are expected of the physician, for the patient is no mere collection of symptoms, signs, disordered functions, damaged organs, and disturbed emotions. [The patient] is human, fearful, and hopeful, seeking relief, help, and reassurance.

So begins Harrison's Principles of Internal Medicine, a dense, 3,600-page two-volume tome that is the nearest thing to a bible in clinical medicine. In its 397 chapters, leading physicians comprehensively explain the diseases of the adult human body and their treatments. My internal medicine professors consult Harrison's regularly. I shall come to know this text well.

I recently saw a documentary (which I recommend) called Jiro Dreams of Sushi. It profiles Jiro Ono, an 86-year-old chef in charge of what is widely considered to be the best sushi restaurant in Japan. Ono explains that he and his assistants make a point of eating the finest food, because how can a chef make excellent food unless he is surrounded by it?

Similarly, if I'm going to practice excellent medicine, I think I will need to surround myself with the finest learning materials. As I've discussed previously, I intend to do more than our curriculum demands. A classmate mentioned that a professor he admires had read Harrison's in its entirety during his training. I thought, why not me? And so, I've resolved to read the whole thing. I've dusted off five chapters in the last 24 hours, which means that only 392 remain. A spreadsheet logs my progress. I predict that I'll finish my undertaking in 12 months. I'm optimistic that it will be worth it. Knowing diseases in depth should help me make some difficult diagnoses and provide good care.