Effects of Tobacco

Slide 1 · Effects of Tobacco

Environmental injury, carcinogenesis, and multisystem pathology

Pathology of toxic exposure and systemic disease

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Teaching objectives

Identify the principal forms of tobacco exposure and the major affected organs.

Explain chemical, nicotinic, hypoxic, inflammatory, and genotoxic mechanisms.

Interpret dose, cumulative exposure, second-hand exposure, and cessation.

Connect mechanisms to malignancy, lung disease, cardiovascular injury, and fetal effects.

Slide 3 · Tobacco injury is a multisystem process

Exposure

Active smoke, smokeless tobacco, or passive inhalation

Toxic mechanisms

Carcinogens, irritants, nicotine, carbon monoxide

Tissue injury

DNA damage, airway inflammation, vascular stress

Disease

Cancer, COPD, vascular disease, fetal injury

Conceptual pathway · editable schematic

Slide 4 · Why tobacco matters in pathology

Smoking as the most readily preventable cause of death.

Disease arises in smokers and in nonsmokers exposed to environmental tobacco smoke.

The same exposure produces malignant and nonmalignant pathologies.

Risk is shaped by dose, duration, route of exposure, and cessation.

Slide 5 · Three clinically important exposure routes

Inhaled cigarette smoke

Direct respiratory mucosal injury

Systemic exposure to smoke constituents

Smokeless tobacco

Oral and mucosal contact with tobacco products

Important association with oral cancer

Second-hand smoke

Inhalation of smoke in a shared environment

Lung, vascular, and childhood respiratory risks

Slide 6 · Cigarette smoking is the dominant exposure

Active inhalation delivers a complex chemical mixture to the airways.

Absorbed constituents also produce systemic effects beyond the lung.

Cigarette smoking as the main contributor to tobacco mortality.

Smoke exposure has both acute physiologic and delayed pathologic effects.

Slide 7 · Smokeless tobacco is not harmless

Products

Snuff and chewing tobacco

Pathologic implication

Direct mucosal exposure and increased risk of oral cancer

Absence of smoke inhalation does not imply absence of carcinogenic harm.

Slide 8 · Second-hand smoke extends risk to nonsmokers

Smoking source

Tobacco combusted in an occupied environment

Passive inhalation

Smoke constituents enter another person’s airways

Biologic effects

Carcinogenic and cardiovascular exposure

Health outcomes

Lung cancer, heart disease, childhood airway illness

Conceptual pathway · editable schematic

Slide 9 · Global tobacco use: 2023 textbook estimate

≈1.3 billion

Smokers worldwide

≈5 trillion

Cigarette-equivalents consumed

2/3

Of smokers in 10 countries

Source estimates · interpretation requires the population and period specified in the lecture notes

Slide 10 · Tobacco consumption is geographically concentrated

China leads the list of high-smoking-burden countries in the source.

India follows, with Indonesia and the United States also listed.

Russia, Bangladesh, Japan, Turkey, Vietnam, and the Philippines complete the group.

This concentration focuses the potential impact of population-level prevention.

Slide 11 · Smoking prevalence has declined globally

Relative decrease in smoking prevalence, 1990–2020

Males

28%

Females

38%

Scale: 0–40% decrease

Slide 12 · Marked declines occurred in several countries

Reported decrease in smoking prevalence, 1990–2020

Brazil

73%

Norway

54%

Senegal

51%

Scale: 0–80% decrease

Slide 13 · Tobacco control is linked to prevalence reduction

Large declines partly to tobacco-control policies.

The WHO Framework Convention on Tobacco Control provides a multinational policy framework.

Prevalence trends vary between countries; Falling prevalence is not universal.

Population exposure and disease burden can remain high despite improvements.

Slide 14 · Global mortality burden

>8 million

Tobacco-attributable deaths per year

≈7 million

Direct tobacco exposure

≈1.3 million

Second-hand smoke exposure

Source estimates · interpretation requires the population and period specified in the lecture notes

Slide 15 · Smoking produces preventable premature mortality

More than 20 million US smoking-related deaths since the 1964 Surgeon General report.

It attributes almost 2.5 million of those deaths to second-hand smoke.

Leading causes of tobacco-related deaths include cardiovascular disease, cancer, and chronic respiratory disease.

These are historical estimates provided by the textbook, not an up-to-date mortality dashboard.

Slide 16 · Tobacco harm increases with cumulative exposure

Dose

Average smoking intensity

Duration

Years of habitual smoking

Cumulative exposure

Pack-years

Risk

Greater cumulative harm with larger exposure

Conceptual pathway · editable schematic

Slide 17 · Pack-years quantify cumulative cigarette exposure

Pack-years = packs per day × years smoked

The source defines this as a cumulative exposure measure.

A pack-year is not a direct biochemical dose of every toxin.

Always collect both intensity and duration in the smoking history.

Slide 18 · Worked clinical exposure example

1.5 packs/day × 20 years = 30 pack-years

The same pack-year figure can arise from different smoking patterns.

It summarizes cumulative history; It does not determine individual risk by itself.

Include ongoing smoking or cessation status in the clinical history.

Slide 19 · Long-term survival differs in smokers

~75%

Of nonsmokers reach 70 years

~50%

Of smokers reach 70 years

Source estimates · interpretation requires the population and period specified in the lecture notes

Slide 20 · Why cumulative exposure is biologically important

Repeated inhalation

Chronic delivery of toxic constituents

Tissue response

Ongoing inflammation and carcinogen exposure

Accumulated injury

Structural and molecular consequences

Clinical disease

Cancer, COPD, and vascular events

Conceptual pathway · editable schematic

Slide 21 · Cessation improves health and lifespan

The source states that stopping smoking improves overall health and longevity.

Cardiovascular mortality declines substantially after quitting.

Lung cancer mortality also falls, but prior exposure creates a prolonged residual excess risk.

Prevention and cessation therefore complement, rather than replace, clinical surveillance.

Slide 22 · Cardiac benefits appear after cessation

During smoking

Higher cardiovascular hazard

After quitting

Exposure and acute physiologic stress diminish

Within 5 years

Heart-disease mortality drops dramatically (Robbins)

Conceptual time course · durations are not drawn to scale

Slide 23 · Lung cancer risk persists after quitting

During smoking

Repeated exposure to carcinogens

After cessation

Further tobacco-smoke exposure stops

Years to decades

Lung cancer excess risk gradually falls; It persists for decades

Conceptual time course · durations are not drawn to scale

Slide 24 · Cessation has different organ-system time courses

Cardiovascular

Marked mortality improvement within the first 5 years after stopping

Lung cancer

Mortality falls after stopping, but excess risk persists for decades

Pregnancy

Normal infant birth weights when smoking stops before pregnancy

Slide 25 · Tobacco smoke is a heterogeneous chemical mixture

≈7,000

Chemicals in tobacco smoke

>60

Identified carcinogens

Source estimates · interpretation requires the population and period specified in the lecture notes

Slide 26 · Different constituents injure tissues differently

Constituent

Major effect in Robbins

Tar

Carcinogenesis

Polycyclic aromatic hydrocarbons

Carcinogenesis

Nicotine

Autonomic effects; tumor promotion

Phenol

Tumor promotion; mucosal irritation

Carbon monoxide

Impaired oxygen transport and utilization

Slide 27 · Airway irritants and carcinogens are distinct

Constituent

Major effect in Robbins

Formaldehyde

Ciliary toxicity; mucosal irritation

Nitrogen oxides

Ciliary toxicity; mucosal irritation

Benzo[a]pyrene

Carcinogenesis

Nitrosamines

Carcinogenesis

Slide 28 · Nicotine is the major addictive tobacco alkaloid

Nicotine is present in tobacco leaves and is strongly addictive.

It binds nicotinic acetylcholine receptors in the brain.

Its autonomic activity provides a mechanism for acute hemodynamic effects.

Carcinogenic risk from smoke also depends on other constituents.

Slide 29 · Nicotinic receptor activation drives acute responses

Nicotine

Tobacco-derived alkaloid

Receptor binding

Nicotinic acetylcholine receptors

Neural signaling

Catecholamine release

Hemodynamic response

Faster heart rate; Higher blood pressure

Conceptual pathway · editable schematic

Slide 30 · Nicotine raises myocardial workload

Nicotine exposure

Autonomic stimulation

Catecholamines

Sympathetic neuronal response

Cardiac effects

Rate, contractility, and output increase

Hemodynamic result

Increased blood pressure and cardiac demand

Conceptual pathway · editable schematic

Slide 31 · Nicotine also creates fetal risk

Nicotine exposure during pregnancy may harm fetal brain development.

The source links prenatal nicotine exposure to increased risk of preterm birth and stillbirth.

These outcomes are not explained solely by adult respiratory disease.

Fetal exposure is an additional reason tobacco injury is multisystem.

Slide 32 · Carbon monoxide compromises oxygen availability

Tobacco smoke

Carbon monoxide exposure

Oxygen transport

Transport and utilization impaired

Myocardial delivery

Less effective oxygen supply

Clinical consequence

Contribution to ischemic stress during smoking

Conceptual pathway · editable schematic

Slide 33 · Ciliary toxicants disrupt airway defense

Smoke constituents

Formaldehyde and nitrogen oxides

Airway surface

Ciliary toxicity and mucosal irritation

Functional effect

Impaired airway clearance and irritation

Disease association

Contribution to smoke-related respiratory pathology

Conceptual pathway · editable schematic

Slide 34 · Tobacco smoke is a leading exogenous carcinogen

Tobacco as the leading exogenous cause of human cancers.

Smoking accounts for a large fraction of lung carcinomas account.

Carcinogenic constituents act through exposure, metabolic activation, and DNA injury.

Organ susceptibility varies with site of contact and distribution of carcinogens.

Slide 35 · Tobacco carcinogens require metabolic interpretation

Inhaled procarcinogens

Tobacco-smoke chemicals

Metabolism

Cytochrome P450 and phase II enzymes

Two consequences

Excretion of some metabolites; Reactive intermediates from others

DNA injury

Electrophiles form DNA adducts

Conceptual pathway · editable schematic

Slide 36 · DNA adducts create a route to oncogenic mutation

Reactive metabolite

Electrophilic carcinogenic intermediate

DNA adduct

Covalent DNA alteration

Error-prone repair

Inaccurate restoration of sequence

Mutation

Potential oncogenic genetic change

Conceptual pathway · editable schematic

Slide 37 · Smoking-related lung cancers show mutational burden

The neighboring Robbins section describes thousands of mutations in sequenced lung cancers from smokers.

Mutational patterns resemble those generated experimentally by tobacco-smoke carcinogens.

This supports a mechanistic link between chemical exposure and cancer genomes.

Tumor genome alterations are evidence of prior injury, not a measure of pack-years by themselves.

Slide 38 · Polycyclic aromatic hydrocarbons are carcinogenic

Chemical group

Polycyclic aromatic hydrocarbons; Benzo[a]pyrene is an example

Pathologic action

Metabolism can produce DNA-damaging intermediates and mutagenic lesions

Airway exposure and systemic distribution help explain cancer at multiple sites.

Slide 39 · Tobacco-specific nitrosamines are organ-relevant

Organ or site

Carcinogens listed in Robbins

Lung and larynx

Polycyclic aromatic hydrocarbons; NNK; polonium-210

Esophagus

NNN

Pancreas

NNK

Oral cavity

NNK; NNN; additional agents depending on exposure

Slide 40 · Bladder cancer illustrates exposure beyond the lung

Tobacco exposure

Systemic intake of carcinogens

Organ-specific susceptibility

Bladder carcinogens listed in source

Examples

4-aminobiphenyl; 2-naphthylamine

Health consequence

Association with urothelial malignancy

Conceptual pathway · editable schematic

Slide 41 · Tobacco-linked cancers involve multiple organs

Site category

Examples listed by Robbins

Respiratory and upper aerodigestive

Lung, larynx, oral cavity, esophagus

Digestive and hepatopancreatic

Pancreas, liver, colon

Genitourinary / reproductive

Bladder, kidney, cervix

Hematopoietic

Hematopoietic malignancies

Slide 42 · Tobacco interacts with additional carcinogens

Asbestos / uranium exposure

Smoking greatly increases lung carcinoma incidence in exposed workers

Alcohol consumption

Combined tobacco and alcohol exposure influences oral and laryngeal cancers

Slide 43 · Cancer risk rises with cigarette exposure

Robbins relates lung cancer risk strongly to the amount smoked and cumulative pack-years.

The source figure illustrates increasing relative risk as cigarettes smoked per day increase.

Avoid converting the figure into an invented smooth curve or extrapolated numerical estimates.

Clinical exposure histories should capture dose, duration, and cessation.

Slide 44 · Smoke directly irritates the tracheobronchial mucosa

Inhaled smoke

Direct mucosal irritants

Airway response

Increased mucus production

Clinical pattern

Bronchitic symptoms and airway dysfunction

Conceptual pathway · editable schematic

Slide 45 · Smoke-related bronchitis involves mucus and injury

Airway response

Mucosal irritation with increased mucus secretion

Functional impact

Symptomatic airway obstruction and impaired clearance

Mucus production is a tissue response; It does not itself establish a cancer diagnosis.

Slide 46 · Inflammatory proteases contribute to COPD

Tobacco-smoke agents

Recruit leukocytes into lung

Inflammatory response

Increase local elastase

Parenchymal injury

Protease-associated tissue damage

COPD phenotype

Emphysema and chronic bronchitis

Conceptual pathway · editable schematic

Slide 47 · Emphysema and chronic bronchitis are distinct

Emphysema

Smoke-induced inflammation and protease-associated injury

Destruction component of COPD

Chronic bronchitis

Airway irritation and increased mucus production

Airway-predominant component of COPD

Slide 48 · Tobacco exacerbates other pulmonary conditions

Smoking exacerbates asthma in the Robbins source.

It is associated with increased risk for pulmonary tuberculosis.

These harms occur in addition to chronic bronchitis, emphysema, and cancer.

A respiratory differential should consider multiple smoking-associated diagnoses.

Slide 49 · Cardiovascular toxicity has multiple pathways

Nicotine

Tachycardia and increased contractility

Carbon monoxide

Reduced effective oxygen supply

Platelets / vascular state

Increased platelet aggregation

Outcomes

Atherosclerosis, myocardial infarction, stroke

Conceptual pathway · editable schematic

Slide 50 · Smoking worsens the oxygen supply–demand balance

Oxygen supply falls

Carbon monoxide-related hypoxia; Coexisting lung disease

Oxygen demand rises

Nicotine-associated increased rate, contractility, and output

Slide 51 · Smoking modifies acute coronary risk

Increased platelet aggregation contributes to cardiovascular disease.

Oxygen supply–demand mismatch compounds ischemic risk.

Robbins also cites a decreased threshold for ventricular fibrillation.

Atherosclerotic complications include myocardial infarction and stroke.

Slide 52 · Other vascular risk factors amplify smoking harm

Smoking

Prothrombotic and hemodynamic stress

Hypertension

Coexisting vascular stress

Hypercholesterolemia

Coexisting atherosclerotic risk

Clinical endpoint

Multiplicative myocardial infarction association

Conceptual pathway · editable schematic

Slide 53 · Maternal smoking has multiple fetal consequences

Pregnancy outcome

Association reported in Robbins

Pregnancy loss

Increased spontaneous abortion risk

Gestational timing

Increased preterm birth risk

Fetal growth

Intrauterine growth restriction

Additional hazard

Stillbirth and possible fetal brain developmental injury

Slide 54 · Preconception cessation matters for fetal growth

Maternal smoking

Increased fetal growth risk

Smoking stopped before pregnancy

Avoidance of continued maternal smoke exposure

Birthweight outcome

Source reports normal infant birth weights in this group

Conceptual time course · durations are not drawn to scale

Slide 55 · Environmental smoke reproduces major disease risks

Passive tobacco inhalation causes lung cancer in nonsmokers.

Exposure is also associated with coronary atherosclerosis and fatal myocardial infarction.

Second-hand smoke is therefore not merely an odor or nuisance.

Smoke-free shared environments address disease risk among nonsmokers.

Slide 56 · Lung cancer and passive exposure: Relative risk

≈1.3×

Relative risk in exposed nonsmokers versus unexposed nonsmokers

Source estimates · interpretation requires the population and period specified in the lecture notes

Slide 57 · Children are particularly affected by home exposure

Adult smoking at home

Shared enclosed-air exposure

Child passive inhalation

Environmental tobacco smoke

Respiratory consequences

More frequent illness, including asthma

Conceptual pathway · editable schematic

Slide 58 · Cotinine indicates absorbed nicotine exposure

Nicotine exposure

Active or environmental tobacco source

Metabolism

Formation of cotinine

Biologic measurement

Blood cotinine concentration

Interpretation

Indicator of tobacco-smoke exposure in nonsmokers

Conceptual pathway · editable schematic

Slide 59 · Smoke-free policies affect biologic exposure

Median cotinine levels in US nonsmokers fell by more than 70% since about 2000.

The text attributes this decline in part to nonsmoking policies in public places.

Household exposure remains an important concern, especially for children.

Population biomarker trends complement self-reported exposure histories.

Slide 60 · Tobacco affects disorders beyond lung and heart

Disorder category

Associations listed in Robbins

Metabolic

Type 2 diabetes

Inflammatory

Rheumatoid arthritis

Ophthalmic

Age-related macular degeneration

Reproductive / sexual

Ectopic pregnancy; erectile dysfunction

Slide 61 · Link each agent to a distinct injury mechanism

Agent / mixture

Predominant injury

Clinical connection

Nicotine

Nicotinic receptor/autonomic effects

Hemodynamic stress; dependence

CO

Impaired oxygen transport / utilization

Myocardial supply limitation

Irritant gases

Ciliary and mucosal toxicity

Bronchitic injury

Carcinogens

Reactive metabolites and DNA damage

Tobacco-associated cancers

Slide 62 · Link major pathology to mechanism

Disease

Relevant pathogenic thread

Lung carcinoma

Carcinogen metabolism → DNA adducts → mutations

COPD

Airway irritation + leukocyte recruitment + proteases

Myocardial infarction

Platelets, oxygen mismatch, and vascular risk factors

Fetal growth restriction

Maternal tobacco exposure during pregnancy

Slide 63 · Case: Interpreting a smoking history

A patient has smoked 1 pack daily for 25 years and now reports a persistent cough.

What exposure measure should be recorded, and what pathologic processes should be considered?

25 pack-years of cumulative exposure.

Airway mucosal irritation with increased mucus; Possible chronic lung disease.

The history is also relevant to lung cancer and cardiovascular risk.

Slide 64 · Case: Smokeless tobacco and an oral lesion

A patient who has never smoked cigarettes regularly uses chewing tobacco and develops a persistent oral mucosal lesion.

Why is the absence of cigarette smoking not reassuring?

Smokeless tobacco is independently harmful.

It as an important cause of oral cancer.

Clinical evaluation of the lesion should not be dismissed based on smoking status.

Slide 65 · Case: Myocardial ischemia in a smoker

A patient who smokes has hypertension and hypercholesterolemia and presents with ischemic chest discomfort.

Which tobacco-related mechanisms may act together?

Nicotine-associated increased myocardial demand.

Carbon monoxide-related oxygen supply limitation.

Increased platelet aggregation and multiplicative risk-factor interaction.

Slide 66 · Case: A nonsmoker with household exposure

A nonsmoker shares a home with a regular smoker. A child in the household has recurrent asthma symptoms.

Which risks and exposure assessment are relevant?

Second-hand smoke carries lung cancer, cardiovascular, and childhood respiratory risks.

Blood cotinine can serve as a marker of absorbed nicotine exposure.

Reducing home smoke exposure addresses a preventable environmental hazard.

Slide 67 · Interpreting textbook risk estimates carefully

The population figures and relative risks are reported estimates 11th edition.

Mechanistic diagrams show causal concepts; They are not experimental plots.

A reported association is not automatically an individual diagnostic criterion.

Population-level associations are not individual deterministic forecasts.

Slide 68 · Three mechanism families explain most damage

Genotoxic

Carcinogens → DNA adducts → mutation

Inflammatory / structural

Airway irritants → leukocytes and elastase → chronic lung disease

Physiologic / vascular

Nicotine + CO + platelet changes → cardiovascular stress

Conceptual pathway · editable schematic

Slide 69 · Clinical synthesis: Tobacco is not a single-organ risk

Assess route, dose, duration, and cessation status.

Consider cancer, obstructive lung disease, vascular events, and reproductive effects.

Remember indirect harm to nonsmokers, especially children and household contacts.

Cessation lowers risk, but long-term malignancy risk does not disappear immediately.

Slide 70 · References and provenance

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th edition (2026).

Chapter 9: Environmental and Nutritional Diseases.

Sections: Effects of Tobacco; Smoking and Lung Cancer; Smoking and Other Diseases.