Environmental pathology
Environmental pathology: smoking, alcohol, occupational dusts, toxins, radiation
Smoking, alcohol, air pollution, occupational lung disease, lead, arsenic, carbon monoxide, radiation and obesity for FCPS Part 1. Each exposure is linked to the mechanism and the disease pattern that examiners test.
Tobacco smoking
- Carcinogens: polycyclic aromatic hydrocarbons (benzo[a]pyrene) and nitrosamines; nicotine causes addiction; carbon monoxide causes hypoxia.
- Cancers: lung (squamous and small cell most strongly), mouth, larynx, oesophageal squamous (with alcohol), bladder, pancreas, kidney, cervix, stomach, AML.
- Non-cancer: centriacinar emphysema (destroys respiratory bronchioles in upper lobes, giving large overinflated lungs with lost elastic recoil; panacinar disease is alpha-1 antitrypsin deficiency), atherosclerosis, Buerger disease, peptic ulcer, osteoporosis, Crohn disease worse.
- Ulcerative colitis is less common in smokers and often appears or flares after stopping. Never advise smoking to control it.
- Smoker's polycythaemia: carboxyhaemoglobin reduces oxygen delivery and shifts the dissociation curve left, so the kidney makes more erythropoietin. SpO2 looks normal and JAK2 is negative; measure carboxyhaemoglobin.
- Smoking in pregnancy: carbon monoxide and nicotine-induced vasoconstriction reduce fetal oxygen delivery, giving growth restriction, a small placenta, preterm birth and abruption. Stopping at any stage helps.
- Varenicline is a partial agonist at alpha-4 beta-2 nicotinic receptors: it relieves craving and blocks the reward of a cigarette. Start 1–2 weeks before the quit date.
- Smokeless tobacco, betel quid, gutka and naswar cause oral submucous fibrosis and oral SCC.
Alcohol
- Metabolised by alcohol dehydrogenase and CYP2E1 (induced by chronic use) to acetaldehyde, then by aldehyde dehydrogenase (blocked by disulfiram) to acetate.
- The high NADH/NAD+ ratio explains fatty liver, hypoglycaemia (no gluconeogenesis) and lactic acidosis. Lactate competes with urate for renal tubular excretion, so a binge can trigger gout; purines in beer add to it.
- Alcohol inhibits ADH release from the posterior pituitary, so large volumes of dilute urine follow drinking. Beer drinkers eating little can get the opposite: hyponatraemia from water excess with low solute.
- Liver: steatosis (reversible; a chronic drinker with normal LFTs usually has fatty change), alcoholic hepatitis with ballooning, neutrophils and Mallory–Denk bodies (eosinophilic clumps of damaged keratin intermediate filaments), then micronodular cirrhosis. AST:ALT over 2.
- GGT is induced by regular alcohol (and by phenytoin and other inducers) and is used to monitor drinking, though a raised GGT alone is not proof.
- Other effects: pancreatitis, Mallory–Weiss tear, varices, Wernicke–Korsakoff (thiamine), dilated cardiomyopathy, macrocytosis, fetal alcohol syndrome.
- Methanol (illicit spirit) is converted by alcohol dehydrogenase to formaldehyde and formic acid, which damages the optic nerve and causes severe metabolic acidosis with an early osmolar gap. Treat with fomepizole or ethanol and dialysis.
Air pollution and carbon monoxide
- PM2.5 (fine particles under 2.5 micrometres) penetrate alveoli and enter the blood, causing systemic inflammation and thrombosis. During Lahore's winter smog, admissions for MI, stroke and COPD rise; most excess deaths are cardiovascular.
- Carbon monoxide (gas heaters in closed rooms): binds haemoglobin about 240 times more tightly than oxygen and shifts the curve left. Pulse oximetry reads carboxyhaemoglobin as oxyhaemoglobin, so SpO2 and PaO2 can be normal; measure COHb by co-oximetry and give 100% oxygen.
- Radon is the second commonest cause of lung cancer; indoor biomass smoke causes COPD in women.
Occupational lung disease
| Exposure | Disease | Key points |
|---|---|---|
| Urban soot, coal | Anthracosis | Black carbon in macrophages of lungs and hilar nodes, no fibrosis, harmless |
| Coal dust (heavy) | Coal workers' pneumoconiosis | Upper lobes; progressive massive fibrosis; Caplan syndrome with RA |
| Silica (stone cutting, sandblasting, quarrying) | Silicosis | Upper-zone nodules, eggshell calcification of hilar nodes; silica kills and impairs macrophages, so pulmonary TB risk rises sharply; lung cancer |
| Asbestos (insulation, shipbreaking, brake linings) | Asbestosis, pleural plaques, mesothelioma, lung cancer | Lower-lobe fibrosis; asbestos (ferruginous) bodies: golden-brown beaded dumbbell rods, iron-coated fibres staining with Prussian blue |
| Beryllium | Berylliosis | Non-caseating granulomas |
| Cotton dust | Byssinosis | Chest tightness on Monday |
| Mouldy hay; birds | Farmer's lung; bird fancier's lung | Hypersensitivity pneumonitis: fever, crackles, not wheeze |
| Flour (bakers), isocyanates (spray painters) | Occupational asthma | Wheeze worse in the working week, better at weekends and holidays; confirm with serial peak flow at work and at home; remove from exposure early |
- With asbestos, lung carcinoma is the commonest cancer and shows the greatest absolute increase in risk (multiplied by smoking); mesothelioma is the most specific. Pleural plaques show exposure, not disease.
Metals and other toxins
| Toxin | Mechanism | Features and treatment |
|---|---|---|
| Lead (old paint, batteries) | Inhibits ALA dehydratase and ferrochelatase (haem synthesis) and pyrimidine 5'-nucleotidase | Microcytic anaemia with basophilic stippling, colic, dense metaphyseal lines, gum lines, wrist drop, encephalopathy. Oral succimer (DMSA) for raised lead without encephalopathy; with encephalopathy give dimercaprol before EDTA |
| Arsenic (tube-well water) | Binds lipoic acid in pyruvate dehydrogenase (blocks energy production) and other thiol enzymes | Raindrop pigmentation, palmar keratoses, Mees lines, painful neuropathy; skin SCC and BCC, lung cancer, angiosarcoma |
| Mercury | Thiol binding | Tremor, erethism, gingivitis, nephrotic syndrome |
| Vinyl chloride | Carcinogen | Hepatic angiosarcoma |
| Benzene | Marrow toxin | AML, aplastic anaemia |
| Aromatic amines (dye, rubber) | Bladder carcinogens | Urothelial carcinoma, the classic occupational cancer |
| Aflatoxin B1 (groundnuts and maize stored damp) | *Aspergillus flavus* toxin; p53 codon 249 mutation | Hepatocellular carcinoma, synergy with hepatitis B |
| Nickel, chromium; wood dust | Carcinogens | Lung and nasal sinus cancer; nasal adenocarcinoma |
- Drug toxicity tied to genes or tissues: aminoglycoside deafness after a single course with normal levels in a family on the maternal side is due to the mitochondrial 12S rRNA variant (m.1555A>G), which makes mitochondrial ribosomes resemble bacterial ones. Long-term glucocorticoids cause osteoporosis mainly by suppressing osteoblast bone formation (and promoting osteoblast apoptosis); start bone protection early.
Radiation, heat and cold
- Ionising radiation damages DNA (double-strand breaks) and makes free radicals. Most sensitive: lymphocytes, marrow, gonads, gut epithelium, lens. Whole-body irradiation causes the greatest marrow suppression.
- Dose estimation: the absolute lymphocyte count falls fastest and in proportion to dose over the first 48 hours; time to vomiting also helps. Haemoglobin falls last.
- Late effects: fibrosis, endarteritis obliterans, cataract, cancers (leukaemia earliest, thyroid after childhood neck irradiation, breast after mantle radiotherapy).
- UVB forms thymine (pyrimidine) dimers, causing BCC, SCC and melanoma.
| Situation | Main route of heat loss |
|---|---|
| At rest in a normal room, unclothed | Radiation (about 60%) |
| Lying on a cold surface or ground | Conduction to that surface |
| Exercising, or hot environment | Evaporation of sweat; humid air blocks it, so athletes in humidity overheat |
- Hypothermia below 35 °C shows J (Osborn) waves. Raynaud phenomenon is digital artery vasospasm on cold or vibration exposure: white (ischaemia), blue (deoxygenation), red (reactive hyperaemia).
Nutrition and obesity
- Protein-energy malnutrition (marasmus, kwashiorkor), and deficiencies of iron, iodine, vitamin A and zinc remain major problems in Pakistan.
- Obesity for South Asian adults: action thresholds are lower because metabolic risk appears at lower weight: overweight from 23 kg/m2 and obesity-related action from 27.5 kg/m2, with lower waist cut-offs. Obesity causes type 2 diabetes, hypertension, NAFLD, sleep apnoea, gallstones and endometrial, breast, colon, kidney and oesophageal adenocarcinoma.
- Diet and cancer: nitrosamines in salted, smoked and pickled food (gastric, nasopharyngeal), red and processed meat (colorectal), aflatoxin (liver), areca nut (oral).
Remember With asbestos, mesothelioma is the most specific cancer but lung carcinoma is the most common.
Exam trap A normal pulse oximeter reading does not exclude carbon monoxide poisoning.
Exam trap Silica impairs macrophages: a silicotic with a new upper-lobe cavity has TB until proven otherwise.
How FCPS asks about this
- Black pigment in hilar nodes, no fibrosis: anthracosis.
- Stone cutter, eggshell nodes, new cavity: silicosis with TB, because silica impairs macrophages.
- Insulation worker with pleural plaques: lung carcinoma has the greatest absolute increase; asbestos bodies are iron-coated fibres.
- Lead poisoning: inhibits ALA dehydratase and ferrochelatase; oral succimer without encephalopathy.
- Arsenic toxicity mechanism: binds lipoic acid in pyruvate dehydrogenase; methanol blinds through formic acid.
- Mallory–Denk bodies: damaged keratin filaments; GGT monitors drinking; alcohol inhibits ADH and lactate raises urate.
- Radiation dose estimate: absolute lymphocyte count over 48 hours; aminoglycoside deafness runs in the maternal line (mitochondrial 12S rRNA).
Test yourself on this topic
5 of the 95 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
After a single short course of gentamicin for pyelonephritis, a 20-year-old woman becomes permanently deaf, although drug levels and kidney function stayed normal. Her mother and maternal aunt also became deaf after aminoglycosides. What explains her susceptibility?
Answer: Mitochondrial 12S rRNA variant
Aminoglycosides bind the bacterial 30S ribosome. Human mitochondrial ribosomes resemble bacterial ones, and the m.1555A>G variant in the mitochondrial 12S rRNA gene (MT-RNR1) makes them even more similar, so normal doses block mitochondrial protein synthesis in cochlear hair cells. Hearing loss can follow a single dose and is irreversible. Because mitochondria are inherited from the mother, the susceptibility runs through the maternal line, and testing before treatment is now advised where available.
Aminoglycoside deafness
- m.1555A>G in mitochondrial 12S rRNA
- Mito ribosome looks bacterial
- Deafness after one dose
- Runs in the maternal line
Remember Familial deafness after aminoglycosides: mitochondrial rRNA.
Exam trap Normal drug levels do not protect carriers of this variant.
Why the other options are wrong
- Autosomal recessive GJB2 mutation Causes congenital deafness, not drug-induced deafness.
- Slow acetylator status Affects isoniazid and hydralazine handling.
- G6PD deficiency Causes haemolysis with oxidant drugs.
- X-linked hearing loss gene Would not show transmission through the mother to daughters.
A stone cutter with 20 years of exposure has progressive breathlessness. Chest X-ray shows upper-zone nodules and eggshell calcification of hilar nodes. Which complication is he especially at risk of?
Answer: Pulmonary tuberculosis
Silicosis results from inhaled crystalline silica (quartz) in mining, quarrying, stone cutting, sandblasting and ceramics. Macrophages ingest silica particles, which damage phagolysosomes and kill the cells, releasing inflammatory and fibrogenic mediators (IL-1, TNF, TGF-beta) through the inflammasome; repeated cycles produce collagenous nodules, mainly in the upper zones, that may coalesce into progressive massive fibrosis. Eggshell calcification of hilar nodes is characteristic. Silica-damaged macrophages make patients more susceptible to tuberculosis (silicotuberculosis), so screening and prophylaxis are considered. Silica is also a probable lung carcinogen and is associated with autoimmune disease. Prevention: wet cutting, ventilation, respirators and medical surveillance.
Silicosis
- Crystalline silica: stone cutting, sandblasting, mining
- Macrophage death → fibrotic nodules (upper zones)
- Eggshell calcification of hilar nodes
- ↑ tuberculosis (silicotuberculosis)
- Prevent: wet cutting, ventilation, respirators
Remember Silica kills macrophages, opening the door to TB.
Why the other options are wrong
- Mesothelioma Asbestos.
- Hypersensitivity pneumonitis Organic antigens such as bird proteins.
- Lower-lobe bronchiectasis Not the typical risk.
- Pulmonary embolism Not the typical risk.
In June, a 22-year-old army recruit in Multan collapses during a long run in full kit. Rectal temperature is 41.8 °C, he is confused and his skin is hot. His airway is safe and IV access is in place. Which of the following lowers his core temperature fastest?
Answer: Cold-water immersion
In exertional heat stroke, organ damage depends on how high and how long the core temperature stays above about 40 °C, so rapid cooling is the priority. Water conducts heat about 25 times better than air, so immersion in cold or iced water removes heat fastest, cooling at roughly 0.15–0.35 °C per minute. Evaporative cooling with spraying and fanning is used when immersion is not possible. Antipyretics do not work because the hypothalamic set point is normal; heat is simply produced and gained faster than it is lost.
Cooling in heat stroke
- Core above 40 °C with CNS dysfunction
- Cool first: cold-water immersion
- Water conducts heat far better than air
- Set point normal: no antipyretics
Remember Exertional heat stroke: cool first, transport second.
Exam trap Do not wait for paracetamol to work; heat stroke is not fever.
Why the other options are wrong
- IV paracetamol Antipyretics lower the set point, which is normal in heat stroke.
- IV dantrolene Used for malignant hyperthermia; no proven benefit here.
- Fan at room temperature Too slow on its own; better with water spray.
- Ice packs to groin and axillae Helpful adjuncts but much slower than immersion.
A 55-year-old who worked for 25 years in a dye and rubber factory has painless visible haematuria. Which cancer is most likely?
Answer: Urothelial carcinoma of bladder
Painless haematuria in an older adult is bladder cancer until proved otherwise. Most bladder cancers are urothelial carcinomas. Risk factors are smoking (the main one) and occupational exposure to aromatic amines (aniline dyes, beta-naphthylamine, benzidine) in dye, rubber and leather industries, plus cyclophosphamide. Chronic irritation from schistosomiasis or long-term catheters causes squamous carcinoma.
Bladder cancer
- Painless haematuria
- Mostly urothelial
- Risks: smoking, aromatic amines
- Dyes, rubber, cyclophosphamide
- Schistosoma: squamous
Remember Dyes and smoking go to the bladder.
Exam trap Cystoscopy is needed for visible haematuria even if a UTI is found.
Why the other options are wrong
- Squamous carcinoma of bladder Linked to schistosomiasis and chronic irritation.
- Clear cell renal carcinoma Possible, but the exposure points to bladder.
- Prostatic adenocarcinoma Rarely presents with painless haematuria.
- Urachal adenocarcinoma Rare; arises at the bladder dome.
During the winter smog in Lahore, hospital admissions for myocardial infarction, stroke and COPD exacerbations rise. Which of the following pollutants is most responsible for this excess cardiorespiratory harm?
Answer: PM2.5 particles
Fine particulate matter under 2.5 µm (PM2.5) penetrates to the alveoli, and the smallest particles enter the blood. It triggers airway and systemic inflammation, oxidative stress, endothelial dysfunction and a prothrombotic state, which explains the rise in heart attacks, strokes and COPD and asthma exacerbations. It is the air pollutant most strongly linked to deaths worldwide. Ozone is a summer irritant, and the gases contribute less to the overall excess mortality.
PM2.5
- Particles under 2.5 µm
- Reach alveoli and blood
- Inflammation, thrombosis, endothelial injury
- Raises MI, stroke, COPD deaths
Remember Smog kills mainly through fine particles.
Exam trap Air pollution harms the heart, not just the lungs; most excess deaths are cardiovascular.
Why the other options are wrong
- Ground-level ozone An irritant gas mainly in sunny summer smog.
- Sulphur dioxide Irritates large airways; less important than fine particles.
- Carbon monoxide Dangerous indoors in closed rooms, not the main smog killer.
- Nitrogen dioxide Contributes to airway irritation but less than PM2.5.
Where this sits in the CPSP syllabus
- Paper 1: General pathology, Environmental and nutritional pathology
- Medicine & Allied, Paper 2: Neoplasia and genetics, Common environmental diseases: smoking, alcohol, pollution, occupational and drug injury
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