The Eventual Doc

Today is day four of my new life as a non-smoker, and with Chantix’s help, it looks as though I’ll be successful. I had, once upon a time, quit for six months (again with Chantix), but turned once again to the Dark Side upon my move to Boston for school. So far, all I’ve noticed is a little bit of grumpiness around mid-afternoon, and I tend to feel lonely for some reason, but otherwise, I’m doing pretty okay on the Chantix.

Everyone (at least, everyone who’s ever smoked) has seen the list of changes over time that occur once a smoker quits, I’m sure. It’s certainly an encouraging list, but it has little in the way of impact for me, as these changes aren’t something you can see, and aren’t really especially detectable in practice. Partially as an exercise for me, but also because I actually enjoy histology and pharmacology, I’ll do my best to contextualize them.

• After two hours nicotine begins to leave your system.

This one’s easy. Nicotine is a plant alkaloid, most commonly derived from the tobacco plant, but also found in certain members of the nightshade family (eggplant, tomatoes, &c.). It is a nicotinic acetylcholine receptor agonist (in contrast to one of its fellow nightshade derivatives, atropine, which is a muscarinic acetylcholine receptor antagonist).

Of course, the quote above is a little silly. Nicotine doesn’t start to get eliminated from the body after two hours. Nicotine clearance begins immediately after exposure. In fact, by two hours post-quitting, roughly half of the nicotine in the bloodstream is eliminated. Nicotine is metabolized in the liver by cytochrome P450 enzymes, embedded in the membrane of the smooth endoplasmic reticulum of hepatocytes.

This metabolism proceeds via first-order kinetics, which means that the relative rate of metabolism remains constant, regardless of concentration. If you were to measure the concentration of nicotine in a smoker’s blood over time after a cigarette, what you would find is that the concentration would drop logarithmically, meaning that the decline would be initially steep, but would eventually level out asymptotically. Plotting the natural logarithm of the concentration as a function of time would yield a straight line with negative slope, and that slope would be equal to the rate constant.

Taking the natural logarithm of two and dividing it by the rate constant yields the half-life, which is the time required to metabolize half a given concentration of the nicotine.

For nicotine, this is equal to roughly two hours. So after about two hours, or one half life, the concentration of nicotine in the smoker’s blood would be one half of the original concentration. After four hours, 1/4. Six hours, 1/8, and so on.

It happens this way because in a first-order reaction, the rate depends upon the concentration of only one reactant, in this case, nicotine. If you imagine the CYP450 enzymes to work so quickly that they can handle an infinite amount of nicotine without getting backed up (they can’t, but that’s a post for another time), then the only thing that would limit the rate at which they could break down the nicotine (barring any allosteric regulation by metabolites or garbage like that) would be the rate at which nicotine finds its way to the hepatocytes. Obviously, the higher the concentration of nicotine, the more will be available to the CYP450 enzymes, the more nicotine per unit time metabolized, and therefore the higher the rate of nicotine metabolism.

What this means, therefore, is that, very roughly speaking, no matter how much a person smoked before they quit, no matter how high their mean level of nicotine, after about two hours, half of it has been metabolized. I say roughly, because this assumes that any upregulation of CYP450 enzymes as a result of chronic nicotine exposure is negligible, and that he or she doesn’t smoke menthol cigarettes, as menthol is a known inhibitor of CYP450 enzymes.

• After 12 hours, carbon monoxide disappears from the body and the blood is able to effectively carry more oxygen to the tissues.

Carbon monoxide is an unfortunate by-product of the incomplete combustion of tobacco. When a smoker breathes it in, he has unwittingly invited into his body a molecule for which hemoglobin, the protein responsible for transporting and distributing oxygen throughout the body, has 250 times the affinity of oxygen. This means that hemoglobin holds onto CO much more readily than it does O₂. This might not ordinarily be a huge problem, except that CO eliminates one of the really neat things about hemoglobin that makes it so good at its job: cooperativity.

Hemoglobin (Hb) is composed of four subunits, two α and two β. Each of these subunits contains a heme group, which is what allows hemoglobin to bind to and carry oxygen. This means that each Hb molecule can carry up to four molecules of O₂. Of course, in order to be a really effective oxygen transporter, Hb needs to be able to respond to different conditions in the body with some degree of sensitivity, grabbing oxygen efficiently when it’s present, but also giving it up easily wherever it’s needed. In order to solve this problem, the subunits of Hb exhibit cooperativity with one another. When one molecule of O₂ binds to a subunit of Hb, it “tugs” on the other subunits, increasing their affinity for O₂, and making it more likely that they’ll hold onto it when it binds. So in areas of high oxygen concentration, Hb will readily and quickly pick up oxygen and hold onto it for transport to other areas of the body.

But the opposite is also true! When Hb reaches an area of the body that needs oxygen, it can readily give it up, and each molecule of O₂ that leaves “relaxes” the other subunits, so that they’re much more willing to give up their oxygen, too. There’s other stuff at play here, like pH and CO₂ concentration, but for our purposes, the cooperativity is what’s important.

Here’s where CO comes in. When CO binds to Hb, Hb tends to hold onto it very tightly. This wouldn’t be too big a deal, except that just like oxygen, CO also tugs on the other subunits, increasing their affinity for oxygen. Not a big deal in areas of high oxygen concentration, but when it reaches areas of low concentration, it’s not as willing to give up its oxygen, because the CO stays bound and keeps tugging on the other subunits, making them a stingier. This is why CO is so dangerous at even relatively low concentrations: You could have plenty of oxygen and still your tissues would be starving for it, as Hb would no longer be very effective at distributing it where it’s needed most!

The only way to get rid of CO is to provide lots of oxygen, and wait for it to leave the body, which it does, albeit slowly.

• Within one week your senses of taste and smell sharpen.

The senses are truly amazing, and I am a little in awe of the ability of evolutionary processes to develop some rather complex functions. In this case, both taste and smell are picked up by cilia on specialized epithelial cells that are connected to the nervous system. It’s not hard to see the advantage bestowed to an organism by the ability of the cells lining its surface to give it information regarding its environment, but it is a little breathtaking to see the elegance with which these cells have adapted to do so.

Below is a picture of a taste bud, and while it’s really beyond the scope of this post to identify which cells are directly involved in taste sensation and which are merely support cells or stem cells, the take-home message is that business end is on the side of the taste pore, the part that projects out into the oral cavity.

The oral cavity would be to the left of this picture, and the tongue, obviously, to the left. In the middle of this picture, you can see a taste bud embedded in the tongue epithelium, with cilia projecting outward through the taste pore.

Cigarette smoke damages these sensory cells, however, which is why taste is typically blunted in smokers. Thankfully, this damage isn’t permanent, and shortly after smoking cessation, taste is largely restored.

There is a similar set-up in the olfactory epithelium, the specialized lining in the nasal cavity that senses smells. It, too, may be damaged by cigarette smoke, making the sense of smell less acute in smokers. A picture of the olfactory epithelium is shown below.

The white space traversing the upper portion of the picture is the nasal cavity, and the strip of epithelium shown traversing from the upper left of the picture to the lower right is the olfactory epithelium. As with the taste bud, there are sensory cells, support cells, and basal cells that act as stem cells, replenishing the epithelium as needed. The cells responsible for sensing taste have cilia-like appendages that project into the nasal cavity, and respond whenever they come in contact with particles of smelly substances by transmitting information to the nerve cells with which they are in contact.

So that’s where I am so far! My nicotine levels have dropped effectively to zero (three full days = 72 hours = 36 half-lives, meaning the concentration of nicotine in my bloodstream is less than 1/2³⁶. This may seem like a gussied-up Xeno’s Paradox type of situation, but trust me, eventually the concentration of nicotine is, in fact, zero), carbon monoxide is back to normal levels (it’s a by-product of a normal process in your body, meaning there’s always some floating around), and my taste and smell epithelia are regenerating.

Additionally, my blood pressure has returned to baseline levels (nicotine is, after all, a stimulant). There are other benefits, but in the interest of readability, I’ll stop here, and save them for an upcoming blog post (with pictures!) about alveoli and respiratory epithelia.

Source: Komaroff, A. L. (1999). The Harvard Medical School Family Health Guide. Cambridge: Simon & Schuster.