Dr. Radu Purtuc is a podiatrist practicing in Trenton, MI. Dr. Purtuc is a medical doctor specializing in the treatment of the foot , ankle and related parts of the leg. As a podiatrist, Dr. Purtuc diagnoses and treats conditions of the feet. The feet are key body parts that give a person stability, absorb shock, allow... more
Nicotine has intrigued me to the point where I decided to investigate it. I've come across many articles and references realizing how far we have come to understanding its intricate mechanisms on physiologic and cellular levels. This is only but a notably brief summary of my lengthy research on Nicotine smoking and its deleterious effects to human body.
A quick search leads to basic facts about Nicotine: first ever records point to French-Portugal trade in 1500's, when seeds of Nicotiana tabacum plant became a trading contributor. Since then, it has been used in recreation, medicine, and as insecticide. By 1900s lung cancer was linked to tobacco smoking. Then its side effects started to be taken seriously as they involved every single aspect of the body, including psychiatric, skin health, soft tissue, blood vessels, dentition, hair loss, and not to mention every single major organ of the body. Not soon enough, it was realized that Nicotine smoking was the most efficient drug delivery system.
Because Nicotine has a very short half-life in serum, meaning it lasts in its active form for few minutes while in the blood stream, the smoker continues to dose frequently, which is at the core of the addiction. And with frequency, comes desensitization, thus with time the smoker is seeking increased concentration of Nicotine to reach the same high.
I briefly mentioned Nicotine use as insecticide, which is formulated at very high concentrations. If ingested, however, this causes death within minutes secondary to asphyxiation due to respiratory failure (paralysis).
- Nicotine from inhaled tobacco reaches the brain between 5-10 seconds.
- Inhaled smoke gets you 90% of Nicotine in bloodstream.
- Only 20-50% of it gets in your blood from smoke taken into mouth and exhaled.
- Nicotine use remains the leading preventable cause of death in the world.
Chronic Nicotine exposure causes long-term homeostatic regulation of endogenous nicotinic acetylcholine receptors (short named nAChRs), which plays a key role in adaptive cellular processes, thus leading to addiction.
In another words, smoking causes a up-regulation of nicotinic acetylcholine receptors, especially of the specific heteromeric receptors non-Alpha7-nAChRs, which by exclusion factor is the Beta2-nAChRs.
You may ask, where are these receptors mainly located? Through tests and imaging studies, these up-regulation of receptors take place in lateral septum, caudate putamen, and nucleus accumbens, or in another words, somewhere inside the brain. Naturally, it is there that our Nicotine seeking takes place, however Nicotine receptors are found throughout our body in every tissue explaining why the effects are so wide spread. 
In another study, it was noted that smoking caused a sharp increase in blood pressure and heart rate. Despite this, there was no notable change in stroke and systemic vascular resistance. Interestingly, smoking caused increase in extremities blood flow, primarily in the muscle and a decrease in blood flow to the skin. This study also showed that in habitual smoker, an increase heart rate was observed.
Why is this important to know? Direct effect of smoking causes short term increase in arterial wall stiffness, which is harmful to artery itself, increasing the risk of plaque rupture. Acute cardiovascular events are mainly due to plaque rupture. This shows that smoking (each time you light up that cigarette) might heavily contribute to acute ischemic events. 
Yet another study talks about the increased aortic systolic blood pressure and increased arterial stiffness. They call to attention reduced pulse pressure amplification and increased arterial wave reflection, all due to adverse hemodynamic effects. All this means blood flow is adversely decreased in extremities primarily the skin. 
What is cotinine?
You may ask, how can a physician tests a patient if previous smoking occurred? It is done by measuring serum cotinine concentrations. A study reviewed serum cotinine acceptable levels, with low levels between 0.2-1.6ng/mL, and the high of above 1.7ng/mL. This procedure is useful when assessing tobacco exposure in children, known as second hand smoking effects. As explained in this study, children with medium to high levels of serum cotinine showed an increase in aortic Young’s elastic modulus and a decrease in aortic distensibility. This report shows a direct relationship between passive smoking and arterial elasticity in children. 
All these previous reviewed studies talk about macrovasculature, i.e. aortic and carotid vessels. Instead, let’s continue by looking at microvasculature, typically those seen in the heart coronary arterial tree, and peripheral microvasculature. The effects of one hour of exposure to tobacco smoke showed a significant decrease in late rise in skin blood flow in response to heating. One way to stimulate the skin’s microvasculature is by directly heating it, which normally should lead to localized vasodilatation and increased localized blood flow. However, this test showed a delayed response of skin to directly warming it, concluding microvasculature was, for lack of better words "in trouble". 
Thus far, we can partially conclude that tobacco smoking specifically increase the macrovasculature (aortic wave reflection) through Nicotine-dependent pathway, and impairs microvasculature function, even past the end of the exposure of Nicotine. In another words the afore mentioned nicotinic effects last for at least minutes to hours after you threw away that finished cigarette. Recalling a previously mentioned fact, while the Nicotine half-life is extremely short, its effects last for relatively long time.
But how is the microvasculature impaired? In a study, researchers concluded that Nicotine directly increases the Norepinephrine NE receptors in the skin capillaries, thus producing vasoconstriction. Do you recall the previously mentioned study where heating up the skin produce vasodilatation? Well, another means to produce similar effect is by use of Nitroglycerine NTG, which is a potent vasorelaxant.
In practice, patients requiring skin incisions, skin flap reconstruction, amputations, and other skin procedures, all will experience a tremendous delay in healing time including complications such as rejection of skin grafts secondary to local vascular spasm and subsequent localized ischemia. Poor vascular flow leads to delayed or blocked delivery of nutrients and removal of normal cellular waste, an important attribute to healing. 
I've always wondered what were the typical effects seen in pregnant women who smoke Nicotine. Several studies investigated such effect. One in particular has shown that smoking caused an acute decrease in intervillous placental blood flow, which had an apparent normalization within 15 minutes. What is expected with decrease blood flow to placenta, even if momentarily? Answer is, direct growth retardation of fetus and other complications of pregnancy including stillborns, premature infants, and low birth weight. 
Besides lung cancer, what ever happens with those smokers who have the typical chronic nagging cough? It turns out that these individuals have an increase lung tissue concentration of macrophages primarily, increased presence of endothelial adhesion molecules, and cytokines. All these inflammatory cellular conglomerate produce symptoms typically seen in non-smokers who are diagnosed with chronic bronchitis.
The bad news is, smokers who decide to quit are expected to continue experiencing these chronic bronchitis symptoms from weeks to months in a row. However, over time respiratory symptoms will decrease dramatically and so will the nagging bronchitis. The good news is overall lung respiratory capacity will improve with time, as seen in greater than 12 months Nicotine free individuals. 
Cause and effect
Risk factors are everywhere. Annals of Internal Medicine defines it in a 1961 article as "something that increases the chance of getting a disease or infection." This however does not take into consideration subclinical comorbidities and subclinical symptoms. A disease becomes apparent when it is symptomatic and negatively interferes with individual's daily life activities. 
In brief, Nicotine is known by many as a major risk factor for many disorders, including cancer, respiratory disease, heart disease, diabetes, stroke, and peripheral arterial or venous insufficiency. This research has in part shown me that the presence of other comorbidities significantly increase the complication rate and speed by which known diseases become symptomatic in nicotinic abusive population.
What does this mean for the patient and the medical team carrying for such patients? It significantly eliminate treatment options, increases the length of recovery, chance of infection, and life expectancy. This in turn makes living difficult for patient and those who care for them, making them harder to comply to medical regiment imposed by medical team. Expectantly, non-compliance is experienced by many patients caught in this tug war of delayed healing time, the outcome being more complications, more interventions, and the cycle repeats to no avail.
1. Long-term effects of chronic Nicotine exposure on brain nicotinic receptors, Morgane Besson, et al., PNAS 2007
2. Short and long-term effects of smoking on arterial wall properties in habitual smokers, Mirian J.F. Kool et al, JACC 1993
3. Effect of Smoking on Arterial Stiffness and Pulse Pressure Amplification, Azra Mahmud, et al, JAHA 2002
4. Decreased Aortic Elasticity in Healthy 11-Year-Old Children Exposed to Tobacco Smoke, Katariina Kallio, et al, JAAP 2008
5. Acute Effects of Passive Smoking on Peripheral Vascular Function, Jean-François Argacha, et al, JAHA 2007
6. The Acute Effects of Smoking on Intervillous Blood Flow of the Placenta, P. Lehtovirta, et al, BJOG 2005
7. Effect of smoking cessation on airway inflammation in chronic bronchitis, G Turato, et al. JRCCM 1995
8. Effect of Nicotine on vasoconstrictor and vasodilator responses in human skin vasculature, Claire E. Black, et al, JRICP 2001
9. The Framingham Offspring Study, H. J. C. Swan, et al, JACC 1999