General pathology · Environmental pathology
Tobacco: how smoking injures tissue !
- Mechanism
Tobacco smoke carries thousands of chemicals that inflame the airways, damage blood vessels and mutate DNA in many organs.
Updated 2026-11-01
What it is
Smoking is the largest preventable cause of cancer and of premature death worldwide. Smoke delivers carcinogens, oxidants and irritant particles to the airway, and absorbed chemicals reach the blood, the vessels and the urine. The result is a pattern of chronic inflammation, metaplasia, atherosclerosis and cancer that spans the lung, mouth, larynx, oesophagus, pancreas, kidney and bladder.
Key facts
- Nicotine causes the addiction; the cancers come mostly from tar carcinogens, not from nicotine itself.
- Lung cancer risk grows with the number of pack-years and falls slowly after quitting.
- Smoking and alcohol multiply each other's effect on head and neck and oesophageal cancer.
- Smoking worsens Crohn disease, while ulcerative colitis is less common in smokers.
- Smoke from wood and other biomass fuels used for indoor cooking also causes COPD, an important cause in rural Latin American women.
Step by step
- Smoke reaches the airway: tar particles, oxidants, polycyclic aromatic hydrocarbons and nitrosamines.
- Cilia slow down, goblet cells multiply and the ciliated epithelium changes to squamous epithelium (metaplasia).
- Oxidants and recruited neutrophils and macrophages release elastase, which overwhelms α1-antitrypsin.
- Alveolar walls break down from the centre of the acinus: centriacinar emphysema and COPD.
- Liver and lung enzymes activate the carcinogens; their DNA adducts cause mutations such as TP53 and KRAS.
- Mutations pile up in the metaplastic epithelium: dysplasia, carcinoma in situ and then invasive cancer.
- Absorbed chemicals injure endothelium, oxidise LDL and favour thrombosis: atherosclerosis and infarction.
- Carcinogens concentrated in urine act on the urothelium for hours: bladder cancer.
Where smoking does its damage
| Organ | Lesion | Main mechanism |
|---|---|---|
| Lung | COPD, squamous and small cell carcinoma | Elastase–antielastase imbalance; carcinogen adducts |
| Mouth, larynx, oesophagus | Squamous cell carcinoma | Direct contact with carcinogens (synergy with alcohol) |
| Arteries | Atherosclerosis, aneurysm, thromboangiitis obliterans | Endothelial injury, oxidised LDL, hypercoagulability |
| Bladder and kidney | Urothelial carcinoma, renal cell carcinoma | Aromatic amines excreted in urine |
| Pancreas | Pancreatic adenocarcinoma | Circulating carcinogens |
| Pregnancy | Low birth weight, placental problems | Nicotine vasoconstriction and carbon monoxide |
Test yourself
Think of the answer, then tap the question to see it.
Which type of emphysema is typical of smokers?
Centriacinar emphysema, worse in the upper lobes, from elastase released by neutrophils and macrophages outweighing α1-antitrypsin.
Why does smoking cause bladder cancer if smoke never touches the bladder?
Absorbed carcinogens such as aromatic amines are excreted in urine and stay in contact with the urothelium.
What change does the bronchial epithelium of a smoker undergo before dysplasia?
Squamous metaplasia: the ciliated columnar epithelium is replaced by tougher squamous epithelium without mucociliary defence.
Which disease of the small arteries of the limbs is almost exclusive to smokers?
Thromboangiitis obliterans (Buerger disease), with segmental inflammation and thrombosis of small and medium arteries.
Related
- Chemical carcinogens: initiation, promotion and the table to know
- Metaplasia
- Oxidative stress and free-radical injury
- Air pollution and occupational exposures
- Multistep carcinogenesis: the adenoma–carcinoma sequence
- Dysplasia and carcinoma in situ
Related conditions
- Chronic obstructive pulmonary disease (COPD)
- Lung cancer
- Laryngeal cancer
- Bladder cancer
- Atherosclerosis and dyslipidaemia
- Tobacco use disorder
- Head and neck squamous cell carcinoma (oral cavity and oropharynx, HPV)
- Oesophageal cancer
- Pancreatic cancer
- Thromboangiitis obliterans (Buerger disease)
- Abdominal aortic aneurysm
- Peripheral artery disease
- Myocardial Infarction (Heart Attack)
- Crohn disease
Elsewhere in DurgiPedia
- Ionizing radiation, tobacco and cocaine
- Reactive oxygen species and antioxidants
- α1-antitrypsin
- Airway defenses, cough and mucociliary clearance
- The airway: from nose to bronchioles
- Oncogenes and tumour suppressor genes
In Pharmacology
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Tobacco and nicotine (World Health Organization, 2026); Risk Factors: Tobacco - NCI (National Cancer Institute, 2026).
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Representative model, for educational purposes only.