My father, a professor of undergraduate human anatomy and physiology, used to stump his class by asking them what the biggest organ of the body is.  The immediate answers—brain, liver, colon—would, of course, all be wrong.  The skin, he’d explain, with its epithelium, sweat and oil glands, hair follicles, and subcutaneous tissue, is the largest organ of the body.  He used this example to define for his class the term organ, then launched into further elaboration of nomenclature such as tissue and organ system.

The skin is the organ we are all most familiar with (we see it every day, after all—can’t exactly say that about the brain, eh?) and recognize this structure in all its variation.  We all know that the pads of our feet are very different from the thin membranes of our eyelids, and no one would confuse the hard, deadened keratin of our nails with the soft, sensitive skin of our lips. 

Diseases of the skin come in a dizzying array of shapes and colors.  An entire medical specialty (with 3 years of dermatology residency training) is predicated on the recognition and treatment of the myriad of moles, rashes, blisters, and lesions that can afflict our outer shell.  When a discoloration or bump pops up on our skin we may not know what it is, but we sure know it’s not supposed to be there. 

We’re also pretty clear about the nature and extent of our skin problems—we know that being cursed with one type of skin malady doesn’t necessarily mean that we’re destined to get them all.  If a doctor tells you that you’ve come down with a case of, say, acne, you wouldn’t immediately assume that your skin will break out in lichen planus, psoriasis, and eczema.  Even the least educated among us recognizes that there are lots of ways our skin can get sick.  In a way we’re all sort of skin experts (because it’s so visible) to a degree that we can’t claim about other organs.  There’s a reason we say “I know that like the back of my hand” and not “I know that like the back of my prostate.”

The heart is clearly a different story.  The public’s understanding of heart disease is pretty one-dimensional, despite the fact that there are dozens of completely unrelated ways in which the function of the heart can be impaired.  For many people, the diagnosis of any one type of heart disease is taken as a declaration that all other cardiac ailments must also be present.  I tell a patient he has a leaky valve and he assumes this means he’ll have a heart attack.  A patient diagnosed with atrial fibrillation (because this involves her heart) goes home and tells her family that she has heart failure and comes back the next week asking about defibrillators and heart surgery.

In order to better help us understand the independence of the various aspects of heart function I’ll use the example of the construction of a house to better explain (I can’t, by the way, can’t claim credit for this metaphor.  I’ve heard this from several other cardiologists and think it’s a pretty clever way to think about the heart).

Structural: The chambers and valves of the heart are the framework of this organ and, like the framework of a house, can have structural problems.  Congenital heart problems, such as septal defects and chamber rearrangements, are like design flaws that put doors and windows in all the wrong places and sticks a bathroom where the kitchen belongs—the early, developing cells of the heart did exactly what the DNA told them to; it’s just the blueprint that was faulty.  Older patients can develop structural problems in hearts that were normal earlier in life.  Examples would be leaky or narrowed valves that lead to inefficient movement of blood through the cardiac chambers.  Just as framework problems in a house are best addressed by carpentry, structural heart problems are often treated with surgery—replace the valve, patch the septal defect, etc.

Electrical: The electrical system of the heart is a separate system altogether and is, of course, akin to the wiring in a home.  Electrical problems come in two main varieties: too much electricity and too little.  More electrical signals lead to rapid rhythm abnormalities and can be treated with medication and ablation procedures.  A shortage of signals results in bradycardia, or slowing of the heart, that is easily fixed with the implantation of a pacemaker.  In the medical world—as in the world of home construction—certain practitioners specialize in problems of an electrical nature (electrophysiologists) and perform the procedures needed to correct both racing and sluggish heart rhythms.

Plumbing: Finally comes the plumbing.  The heart muscle receives its supply of oxygen and nutrients not from the gallons of blood it pumps every day, but rather through its own set of arteries that arise from the aorta just as the blood is pumped out of the ventricle.  Plug up just one of these miniature conduits and you suffer a heart attack.  The plumbers in our trade are the interventional cardiologists who specialize in putting very small stents in very small spaces.

While it’s true that there are certain areas of overlap in function, many of the cardiac disease processes tend to afflict the heart in isolation.  A patient with atrial fibrillation (electrical) doesn’t necessarily have any higher risk of heart attack (plumbing) than someone with normal rhythm.  Aortic valve stenosis (structural) has no immediate correlation with, say, supraventricular tachycardia (electrical) or coronary disease (plumbing).

Outside forces can affect all three subdivisions.  A good example is uncontrolled hypertension which will eventually lead to left ventricular hypertrophy (structural) and serves as a risk factor for heart attack and stroke (plumbing).  Atrial fibrillation (electrical) is more prevalent among patients with uncontrolled hypertension because the long-standing pressure exerted on the delicate left atrial chamber ultimately expands this chamber (structural) and makes the muscle more electrically irritable.

While the heart may not have as many unusual syndromes as the skin (or as many bizarre names, to wit “pityriasis lichenoides et varioliformis acuta”) it clearly has a variety of categories in which problems can arise, categories that often represent separate and unrelated issues.  To those of you with heart problems I encourage you to educate yourself on both what you have as well as what you don’t have.  Ask your doctor how your illness and your medications affect the other functions of the heart.  Find out what you need to know to be as educated about your heart as you are about your skin—get to know your heart as well as you know the back of your hand.

In one week (April 19th) my wife and I will be running the Boston Marathon.  Neither of us is hoping to post a record time.  Mainly, we’re looking to finish without collapsing and with as few blisters as possible.  People I’ve told of this tend to be congratulatory of our effort and remark how admirable it is that we’re able to do this.  In fairness, it is a bit of an accomplishment to be able to even enter the Boston Marathon since this famed race is open only to competitors who’ve already posted a reasonable time in a marathon within the previous year (3:20 for me).  Thus, in my view, the hardest thing about the Boston is that in order to run it you have to actually train for two marathons—the Boston Marathon itself, plus one prior marathon to qualify.

I love watching the elite marathoners as they glide by at their amazing pace.  They move like gazelles and make running look as effortless as an eagle soaring on a high thermal wind.  Whenever I see them I have to remind myself how fast they are actually moving.  The per-mile pace for the winners of the big marathons is somewhere around (or below) 5 minutes, a pace that most competitive high school runners have trouble with for a single mile.  The standing world record, set by Haile Gebrselassie at the 2008 Berlin Marathon, is 2 hours, 3 minutes, 59 seconds.  That translates to an average of under 4:45 per mile for the entire 26.2 mile course.  That, to me, is mind boggling.

But while I look in awe at these magnificent runners I can’t say that they are the ones I admire most.  Runners like Gebrselassie are typically about 5’9” and weigh around 135 pounds (this is really the ideal build for an accomplished long-distance runner) and have logged thousands and thousands of miles during their lifetime.  In one book I recently read the author mentioned that most elite African runners have already logged nearly 20,000 miles of running by the time they reach college age.

So for guys like this who are essentially born to run, how hard is it really to spend a couple hours out running in a race?  I don’t mean to diminish the accomplishment of running 26 miles in under two and a half hours (the typical men’s winning time for marathons), but I don’t really swoon in admiration for a 135 pound cheetah for whom running is as natural as using the restroom.

The people I really admire are far different.

The pain of the marathon is not the 26 miles you have to cover, but rather the time that you have to spend putting one foot in front of the other.  By that metric, the people who suffer most (and therefore have to overcome most) are those who spend the longest time on the course—the 4- and 5-hour marathoners.  Add to this the fact that most marathons start around 7 a.m. and are therefore blazing hot by the time 11 a.m. rolls around.  While the elite runners are rehydrating in the massage tent and dreaming of their next race, the bulk of the marathon population remains on the course, pounding and sweating away through the slowly advancing miles.

And these are not lithe, wispy 135-pound bodies out there.  Real humans, with aching knees and sagging midsections, make up the majority of marathoners.  These are people who do not look like nature has created them to coast through mile after mile of race course, yet they do.

One example is my friend Loren Gress.  He’s a former professional baseball player who’s built like a model first baseman, but at 6 foot 7 inches and 210 pounds he’s hardly the image of an accomplished marathoner.  Despite his less-than-optimal proportions he manages to get out for runs day after day and even in the most miserable weather conditions.  A couple of years ago he developed pain in the hip while running the Lincoln Marathon and was ultimately diagnosed with fracture of the labrum of his pelvis.  Surgery followed as did many weeks of no weight-bearing and he’s now back on the road tuning up for this year’s Lincoln.  By the time Loren crosses the finish line (with pelvis hopefully intact) the winner (probably a thin little guy from the NU cross-country team) will have already packed up his gear and headed home, but it’ll be Loren who gets my admiration.

The same is true for my brother-in-law, Mark Thurber, a 55-year-old corporate lawyer from Houston.  He took up distance running a couple of years ago and has already completed 4 marathons.  His first race lasted a painful 5 hours, 51 minutes, but he’s steadily improved his times to the point where he is consistently finishing at around 4 hours.  With his training he’s managed to trim himself from 200 pounds down to 170.  Mark’s goal is to qualify for the Boston Marathon and I’m pretty sure he’ll get there. 

My wife Cheryl is another story of triumph over adversity.  She had qualified for the Boston Marathon by running the local Omaha Marathon 18 months ago.  While training over the summer she developed incapacitating hip pain.  Thinking it was one of the numerous aches and pains that runners suffer, she simply rested a while and continued with her training.  Weeks later an MRI of her pelvis confirmed a severe fracture of the sacrum.  Like Loren, she spent weeks with crutches, hobbling around the house as the bones came together.  Over time she began walking, then running, and is now up to longer distances at a gentle pace.  Next week’s marathon will be the first race she’s done since her injury.  I will be at her side through the whole race making sure she takes it slowly enough (are you reading this, honey?).

You may not believe this, but there is a raging debate among the more high-brow marathoners about my slower colleagues.  Critics believe that allowing slower runners (or “run-walkers”) to enter and complete a marathon diminishes the hallowed tradition of marathoning for everyone else, as is illustrated by this piece in the New York Times:

Purists believe that running a marathon should be just that — running the entire course at a relatively fast clip. They point out that a six-hour marathoner is simply participating in the event, not racing in it. Slow runners have disrespected the distance, they say, and have ruined the marathon’s mystique.

“It’s a joke to run a marathon by walking every other mile or by finishing in six, seven, eight hours,” said Adrienne Wald, 54, the women’s cross-country coach at the College of New Rochelle, who ran her first marathon in 1984. “It used to be that running a marathon was worth something — there used to be a pride saying that you ran a marathon, but not anymore. Now it’s, ‘How low is the bar?’ ”

I find this absurd.  Anyone who spends 6 hours traveling 26 miles on hot pavement deserves as much (and, I think, more) praise as those of us who can cover the distance in 3 hours.  Keep in mind that most of these slower runners have actually overcome more to get where they are than the elite runners.

I’ll take my opinion one step further and challenge my readers to expand the ranks of slow marathoners.  For those of you who aren’t runners I challenge you to pick a race, pick a distance, and set the goal of entering one of these events.  Give yourself a half year to get your body in shape and keep your expectations realistic.  Then go finish a half- or full-marathon, even if it takes you half the day.  The sense of accomplishment will be immeasurable; the positive effect on your body will surprise you; and you’ll love the energy and the atmosphere of the race.

So thanks to all those who congratulate me on my upcoming marathon, but with my lean, tall frame and years of running it’s not real much of an accomplishment for me to finish another marathon.  The real heroes are those of you who take up the challenge of running and tackle something that only a small segment of the population can claim, even if it takes you longer than 2 hours and 3 minutes.

“The good news: It’s not your heart.  The bad news: I don’t have a clue what it is.”

The first half of this statement is heard every day in emergency rooms and doctors’ offices across the country.  The second half may involve a little more honesty than most doctors want to admit.

You come to the ER with chest pain (CP) worried that it might be your heart.  They hang on to you for a few hours, do several tests, and conclude that your worst fears—that you’re in the throes of a massive heart attack or something similar—are not founded. 

The job of the ER doctor in this scenario is really two-fold.  First, determine if you have a life-threatening emergency and, if so, initiate treatment.  Second, if your symptoms aren’t the harbinger of certain doom the ER doctor has to come up with a diagnosis to give you and to put on the chart.  The first part of this equation is actually pretty easy in most situations—we have well-established algorithms to guide the evaluation and exclusion of a relatively short list of dangerous things that can cause CP.

It’s the second part—if it’s not your heart, then what is it?—that is the real challenge.  Most doctors will offer a diagnosis but in many cases it’s their best effort at a blind guess.  You can’t really blame them for trying.  No doctor wants an unsatisfied patient and, of course, no patient wants to go home without a diagnosis, especially after seeing how much they owe in co-pay.  It’d be like taking your car to auto mechanic who charges you a thousand dollars only to tell you “Well, it ain’t your transmission.”

So, if the CP isn’t coming from a blocked artery, what exactly is it?  We first rule out other potentially life-threatening or immediately reversible ailments.  Most of these are fairly easy to detect with simple screening tests or discernible based on the patient’s account of their symptoms:

Aortic dissection.  A tearing or rupture of the aorta that comes spontaneously (most often in patients with a history of high blood pressure) and is lethal in about 50% of cases.

Pulmonary embolism.  A blood clot, generally arising in the veins of the legs, lodges in the arteries of the lungs.  CP, shortness of breath, and cough are clues to this problem.  It is fatal (if untreated) in about a quarter of patients.

Spontaneous pneumothorax.  This is a relatively rare problem where the lung deflates without apparent cause.  It is easily detected on chest x-ray and, while not as deadly as other problems, needs to be treated relatively quickly.

Pneumonia.  This one doesn’t really fall into the “urgent” category like the others, but it is serious and the diagnosis needs to be entertained in patients with CP.

After that, you’re left with a long list of benign problems that can lead to CP.  Here is a partial list of the more common causes of benign noncardiac CP and a brief descriptor of each:

Esophageal pain.  This is a broad category of painful problems relating to a structure that sits right behind the heart and is served by the same pain nerves as the cardiac muscle.  Esophageal reflux, spasm, hiatal hernia, achalasia, and functional dyspepsia can mimic with protean precision all the symptoms of a heart attack.  Spasm, in particular, can be challenging since it also responds quite quickly to administration of nitroglycerin (this is partially why a positive response to nitroglycerin is utterly useless in helping us isolate the cause of discomfort).  About 60% of patients with CP will have an esophageal problem as the source.

Costochondritis.  The costochondral junction is where the ribs attach to the sternum (breastbone) and can be afflicted with inflammation and joint aches just like the knee, hip, and any other skeletal junction of the body.  Pain can mimic angina, but can also be tender to touch and worse with movement or deep breathing.  Costochondritis is a somewhat unglamorous cause of pain and leads to no dangerous problems.  As you muse over health problems with acquaintances at cocktail parties you may wish to invoke the more exotic moniker of Tietze Syndrome when referring to your ills.  Your friends will be more impressed as they take a step back from you and wipe their hands on their pants.

Pleurisy.  Inflammation of the lining of the lung can lead to severe, stabbing pain anywhere in the chest, most often exacerbated by deep breaths and body movement.  There’s no test to pinpoint this (the diagnosis is made based on the description of pain and the absence of other problems) and treatment consists of antiinflammatory medications such as ibuprofen and indomethacin.  Pleurisy’s cousin is inflammation of the lining of the heart (pericarditis) and can present with similar symptoms.

Herpes zoster (shingles).  Early in the course of this demonic ailment a patient will have severe focal pain and tenderness days before the characteristic rash appears.  Successful treatment depends on early suspicion and administration of antiviral drugs. Clinicians need to keep this disease in mind when seeing older patients with CP limited to one side.

Fibromyalgia.  This is an entity nearly everyone has heard of but no one really understands.  Chronic CP is a common feature.

Radiculopathy.  Strain your cervical spine and you could pinch or compress one of the nerves that serve the chest wall, shoulders and neck.  The pain’s not terribly similar to pain from the heart, but since it frequently travels down the arm or into the jaw it can be confusing for patients and clinicians.

Muscle strain.  At some point in their lives virtually every person will pull a muscle and suffer pain for a few days or longer.  There are dozens of muscles that attach to the chest wall (including layers of muscles that bind the ribs together) and any one of them could serve as the source of significant discomfort.

Somatic causes.  Somatic is a polite, professional way of saying it’s all in your head.  It’s well known that depression, anxiety, and panic attacks can cause a patient to quite literally experience all the symptoms of a heart attack.  This was first described as a cause of CP among veterans of the American Civil War by a doctor named Jacob Mendes Da Costa who observed these symptoms in patients whose psyche had been ravaged by the stress of war (Da Costa syndrome is also termed “soldier’s heart”).  In my experience this sort of thing can affect even the most balanced, sane, calm individuals and is not limited to crazy people.  Personally, I resist the urge to make the diagnosis of “stress-related” pain since I don’t remotely consider myself an expert in psychiatry or stress disorders (despite my use of the highly technical term “crazy people”).

One thing that all these benign causes of CP have in common is that they are extremely difficult to diagnose with any degree of certainty.  Most often we arrive at these conclusions by excluding other, more easily diagnosed problems.  As I’ve stated in a previous post, modern medicine is very good at telling you what you don’t have and not so good at pinning down what you’ve got, especially if it doesn’t lead to death or permanent impairment.

So, breath easy (that is, if it doesn’t hurt to take a deep breath) if the doctor tells you it isn’t your heart—that is indeed good news.  Just be prepared for a little frustration if you want to find someone who can definitively tell you what it is rather than just what it isn’t.

While reading the New York Times last week I came across an article announcing the passing of Dr. James W. Black, a noted Scottish pharmacologist, and while I am reluctant to write two drug-related blog posts in a row I feel obliged to dedicate a few words to his accomplishments.

(Of note, those of you fond of the world of pharmacology history may enjoy previous posts on nitroglycerin, warfarin, digitalis, and aspirin.  For those of you who have no interest in this, count yourself lucky)

Back in the mid-1950s doctors were eager to have more choices available to treat cardiac angina.  Nitroglycerin had existed in one form or another for several decades but fell short of providing adequate relief for many with coronary stenosis.  Coronary artery bypass surgery (CABG) was yet to be developed and the advent of catheter-based coronary repair (angioplasty, stenting) was decades away.

While most researchers in the field were looking for ways to increase the amount of oxygen-rich blood available for starving heart muscle, Dr. Black sought a different approach.  He theorized that one could improve a patient’s chest pain by decreasing the metabolic demand of the heart and consequently allowing the muscle to function on less blood. 

Scientists had already worked out the concept of cardiac muscle protein receptors that bind adrenalin and noradrenalin (epinephrine and norepinephrine), but the clinical scientific community was not focusing in this direction.  Dr. Black expanded on the existing research and sought a chemical that would specifically target the beta-adrenergic receptor—the trigger of the so-called “fight or flight” response.

His initial attempt yielded pronethalol, a substance that quite nicely blocked the beta-receptor and relaxed the contractile work of the heart.  Unfortunately this chemical was also quite toxic.  In 1964 Dr. Black developed the first safe and effective beta-blocker, and nine years later propranolol (Inderal) entered the US market as the pilot drug in a class that has come to be a mainstay in the world of cardiology.

For his work Dr. Black (and two others) was honored with the Nobel Prize in Medicine in 1988, but he didn’t stop there.

After his success with propranolol in 1964 he immediately launched an effort at producing a chemical that would block the production of stomach acid.  The fruit of his efforts to block the H2-receptor in the lining of the stomach was the drug cimetidine (Tagamet).  Those of you old enough to remember the “plop plop fizz fizz” jingle will recall what a breakthrough this development represented in 1979.  Thousands of patients suffering from ulcers and intractable reflux were spared the surgeon’s blade by adopting the use of this class of drugs (called H2 blockers—Zantac, Pepcid, and the like).

Dr. Black was knighted in 1981 and, after creating the world’s first blockade of stress on the heart and on the stomach, he spent some time as a university chancellor and then transitioned into retirement. I can’t think of another researcher who nearly single-handedly came up with two seminal medical therapies in unrelated fields.  It would be like Guglielmo Marconi discovering the transistor radio and the iPod.  Or like the Wright brothers developing the airplane and in-flight movies.  Or like Thomas Edison inventing the light bulb and the phonograph.  Oh, wait.  I guess Tom Edison did do that.

If only Dr. Black had enjoyed his youthful scientific curiosity longer I’m sure he’d have come up with cures for cancer, the common cold, baldness, and the nerdy desire to post blog articles every week.

Now it’s time to segue into the clinical portion of my article and focus a little on beta-blockers.  While propranolol was first in its class it is no longer widely used because of its frequent side effects.  It’s still prescribed to migraine sufferers, people with benign hand tremors and those who suffer from excessive perspiration when engaging in public speaking (I’ve never tried it for this but people tell me it works wonders).

Cardiac angina is considerably less common these days because most people with lifestyle-limiting coronary disease can receive full resolution of their symptoms with stent placement or bypass surgery.  Hypertension remains a common indication for the more modern beta-blockers such as metoprolol (Lopressor) and atenolol (Tenormin).  These medications can also treat the palpitations associated with atrial rhythm abnormalities such as atrial fibrillation.

Of interest is the use of beta-blockers in congestive heart failure.  As recently as the early nineteen nineties, when I started my internship, these drugs were regarded as contraindicated in patients with weak hearts.  It stands to reason if you think about it: adrenalin increases the frequency and vigor of cardiac contraction, and blocking this effect will slow and weaken the resulting pulse.  In medical school we were taught to assiduously avoid beta-blockers in these individuals.

But it turns out that just the opposite is true.  Think of beta-adrenergic stimulation (with adrenalin and noradrenalin) as the big, burly guy who beats the drum on the old Roman slave ships.  Sure, his incessant percussion frightens the frail slaves into rowing faster for a while, but after a time it just leads to early fatigue and failure of the system.  Patients with heart failure actually have higher than normal levels of adrenalin in their system—their bodies sense the low blood flow and release the hormone hoping to squeeze out a little more cardiac output.  Over time, though, the constant whipping of the heart leads to deterioration of the muscle cells and worsening of heart failure.

Numerous studies have demonstrated the benefit that comes from giving the heart a reprieve by adding certain types of beta-blockers such as carvedilol (Coreg) and extended-release metoprolol (Toprol XL).  Weak hearts can actually heal over time (to some degree, anyway) if you remove the stress of adrenalin.  In the world of congestive heart failure, beta-blockers have now emerged as the cornerstone of therapy.

I’ve been unable to find any interviews with Sir James Black in the last years of his life and I’d be interested to hear what he thought of the durability of his discoveries.  Decades later, beta-blockers and H2-blockers remain incredibly common and useful.  Dr. Black should be proud of his accomplishments.