Smoking
Facts
tobacco accounts for 390K premature deaths per year and is the cause of 10 million chronic diseases
smoke contains 4000 chemicals; 60 ID’d as carcinogens; also formaldehyde, HCN, CO, metals
CO: binds to Hb with 200x affinity of oxygen; also binds to myoglobin and cytochrome oxidase
nicotine: stimulates nicotinic receptors in brain and elsewhere
chemicals can pass mucus membranes, alveoli, or be swallowed
there is a dose-response relationship
stopping first increases risk, then decreases
could be that patient stopped because sick; or stop
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cell repair
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high cell prolif
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mutations
30% of cancer deaths and 90% of lung cancer deaths may be caused by smoking
is multiplicative risk factor in MI, stroke (the pill), resp infections, pregnancy (fetal hypoxia), etc.
also synergy with many other chemicals
cigar and pipe smoke is alkaline, so nicotine deprotonated and can cross mucus membranes easily
cigarette smoke is acidic, so must inhale to get same amount of nicotine
Diseases Caused by Smoking
cancer of lung, mouth, pharynx, larynx, esophagus, kidney, bladder, pancreas
ischemic heart disease; MI; arteriosclerosis; COPD
50% survival rate for lung cancer = 6 months
Relative risks to smokers:
lung cancer – 22
lip, oropharynx, larynx – 27
COPD – 10
coronary artery disease – 3
Emphysema
: abnormal permanent enlargement of airspaces distal to terminal bronchioles and destruction
of walls without evidence of fibrosis (without destruction
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overinflation)
centriacinar
: proximal parts of acini (respiratory bronchioles) are affected; distal alveoli are spared
panacinar
: alveoli are uniformly enlarged from respiratory bronchioles to terminal alveoli
probably results from inbalance between elastase and anti elastase
elastase released by neutrophil and macrophage
smokers have more neutrophils and macrophages in the lung
nicotine stimulates elastase release from neutrophils
smoking enhances protease activity in macrophages
free radicals in smoke and neutrophils inhibit antielastase (
a
1
-TA)
Chronic Bronchitis
could cause COPD, cor pulmonale and heart failure, metaplasia and dysplasia or respiratory epithelium
persistant productive cough (hypersecretion of mucus)
two factors: (1) chronic irritation (smoke); (2) microbiologic infection (secondary, smoking
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risk)
hypersecretion of mucus in smaller airways can lead to COPD
histology: goblet cell metaplasia
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mucus plugging; increased dust cells; inflammation; fibrosis
Smoking and Cancer
statistical evidence
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risk depends on:
amount of daily smoking
tendency to inhale
duration of smoking habit
initiator: causes permanent injury to DNA
promoter: causes tumor growth after an initiator exposure does not cause tumor growth
smoke contains both initiators and promotors
squamous cell carcinomas
95% are in mouth
smoking and alcohol act synergistically
often caught late; 50% are fatal
Microsomal Mixed Function Oxygenase System (MFO)
cytochrome P450 dependant; can convert chemicals either to active or inactive form