Environment and Lifestyle Related Pathology

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A. O ccup ation-Associated Pneum oconiosis

1. Pneumoconioses a. Definition: fibrosing pulmonary diseases caused by inhalation of an aerosol (mineral dusts, particles, vapors, or fumes)

b. Key factors i. Type of aerosol and its ability to stimulate fibrosis ii. Dose and duration of exposure iii. Size of the particle

2. Coal-worker's pneumoconiosis a. Occupation: coal mining b. Anthracosis i. Carbon pigment (anthracotic pigment) accumulates in macrophages along the pleural lymphatics ii. Asymptomatic c. Simple coal worker's pneumoconiosis i. Synonym: black lung disease ii. Coal-dust macules and nodules in the upper lobes iii. Little pulmonary dysfunction d. Complicated coal worker's pneumoconiosis i. Progressive massive fibrosis ii. Increasing respiratory distress iii. Pulmonary hypertension and cor pulmonale e. Caplan syndrome: pneumonconiosis plus rheumatoid arthritis

3. Asbestosis a. Family of crystalline silicates i. Serpentine

■ Curved, flexible fibers

• Most common type: chrysotile ii. Amphibole

■ Straight, brittle fibers

• Types: crocidolite, tremolite, and amosite

• More pathogenic and highly associated with mesotheliomas b. Occupations: shipyard workers, insulation and construction industries, brake-lining meclical 83

c. Lung pathology i. Diffuse interstitial fibrosis, which is most severe in the lower lobes ii. Asbestos bodies that may become coated with iron (ferruginous bodies)

iii. Slowly progressive dyspnea iv. Pulmonary hypertension and cor pulmonale d. Fibrous pleural adhesions e. Pleural plaques f. Bronchogenic carcinoma i. Most common tumor in asbestos-exposed individuals ii. Synergistic effect of smoking and asbestos exposure g. Malignant mesotheliomas i. Rare highly malignant neoplasm ii. Occupation exposure to asbestos in 90% of cases iii. Presents with recurrent pleural effusions, dyspnea, chest pain iv. Gross: encases and compresses the lung v. Micro: carcinomatous and sarcomatous elements (biphasic pattern)

vi. EM: long, thin microvilli vii. Poor prognosis h. Increased risk of laryngeal, stomach, and colon cancers i. Family members also have increased risk of cancer Caplan syndrome

. Silicosis a. Occupations: sandblasters, metal grinders, miners b. Exposure to silicon dioxide (silica)

c. Pathology i. Dense nodular fibrosis of the upper lobes ii. Birefringent silica particles can be seen with polarized light iii. May develop progressive massive fibrosis d. Clinical course i. X-ray: fibrotic nodules in the upper zones ii. Insidious onset of dyspnea iii. Slowly progressive despite cessation of exposure e. Increased risk of tuberculosis f. Caplan syndrome Berylliosis a. Occupation: aerospace industry and nuclear reactors b. Etiology i. Beryllium exposure ii. Genetic susceptibility iii. Type IV hypersensitivity reaction, resulting in granuloma formation c. Acute exposure: acute pneumonitis d. Chronic exposure i. Pulmonary noncaseating granulomas and fibrosis ii. Hilar lymph node granulomas iii. Systemic granulomas

Table 10-1. Industrial Toxins

Industrial Toxin

Occupation

Pathology

Soot (polycyclic aromatic hydrocarbons)

English chimney sweeps

Scrotal cancer

Vinyl chloride

Plastic industry

Angiosarcoma of the liver

Uranium and radon gas

Miners

Lung cancer

(3 - Na p hthylami n e

Dye makers and rubber workers

Bladder cancer

Benzo[a]pyrene

Steel mills and cigarette smoke

Lung and bladder cancer

Carbon tetrachloride

Dry cleaners

Liver and kidney toxicity

Organophosphates

Farmers

Irreversible cholinesterase inhibitors

B. Adverse Drug Reactions

1. Aspirin a. Pathology of acute toxicity i. Common cause of overdose Ln children (accidental) and adults (suicide)

ii. Headache, tinnitus, vomiting, tachypnea, and confusion iii. Respiratory alkalosis and metabolic acidosis iv. Seizures, coma, and death b. Pathology of chronic toxicity i. Acute erosive gastritis and upper GI bleeding ii. Bleeding tendency due to reduced platelet aggregation

2. Estrogens a. Hormone replacement therapy (HRT)

i. Benefits of HRT

■ Decreased osteoporosis • Decreased ischemic heart disease ii. Unopposed estrogens have an increased risk of endometrial and breast carcinoma b. Oral contraceptives i. Increased risk of DVT and thromboembolism in smokers ii. Oral contraceptives have a decreased risk of ovarian and endometrial cancer iii. Slight increase in risk of breast and cervical cancer

C Poisoning

1. Carbon monoxide a. Sources: auto emissions, home heaters, byproduct of fires, cigarette smoking b. Pathogenesis i. Odorless, colorless gas ii. High affinity for hemoglobin iii. Forms carboxyhemoglobin, which shifts the oxygen dissociation curve iv. Causes systemic hypoxia c. Symptoms depend on the concentration i. 10% —> asymptomadc ii. 30% —» headache and shortness of breath on exertion iii. 50% —»loss of consciousness, convulsions, and coma iv. 60% death d. Bright "cherry-red" color of the skin, mucosal membranes, and die blood e. Treatment: oxygen

2. Mushroom poisoning a. Amanita muscaria—recovery with supportive therapy; rarely lethal b. Amanita phalloides i. Toxin (amanitin) inhibits RNA polymerase ii. Abdominal pain, vomiting, and diarrhea iii. Fulminant hepatitis with extensive liver necrosis iv. Coma and death

3. Arsenic poisoning a. Can be detected in hair and nails long after exposure b. Acute poisoning i. Hemorrhagic gastroenteritis ii. CNS toxicity —» coma and seizures iii. "Garlic-seen ted" breath c. Chronic poisoning i. Malaise and abdominal pain ii. Peripheral neuropathy and muscular weakness iii. Skin changes (hyperpigmentation and dermatitis)

iv. Mees lines: transverse bands on the fingernads d. Complications: squamous cell carcinoma of the skin and lung

4. Lead poisoning (plumbism)

a. Epidemiology i. Most common type of chronic metal poisoning in the United States ii. Primarily affects children in poor urban areas b. Sources: lead paint, lead plumbing, and leaded gasoline c. CNS toxicity i. Lethargy and somnolence ii. Cognitive impairment and behavioral problems iii. Mental retardation iv. Cerebral edema —> encephalopathy d. Wrist and foot drop occur in adults due to peripheral motor nerve demyelination e. Abdominal pain (lead colic)

f. Renal tubular acidosis and renal failure g. Microcytic anemia with basophilic stippling h. Deposition of lead at the gingivodental line ("lead line")

i. X-ray: long bones have lead lines (increased bone density) at the epiphyseal growth plates j. Diagnosis i. Blood lead levels ii. Increased free erythrocyte protoporphyrin k. Treatment: chelating drugs

5. Mercury poisoning a. Neurotoxicity i. Intention tremors ii. Dementia and delirium ("mad as a hatter")

b. Nephrotoxicity (acute tubular necrosis)

6. Cyanide poisoning a. Clinical finding: "bitter almond" scented breath b. Mechanism: blocks cellular respiration by binding to mitochondrial cytochrome oxidase c. Systemic asphyxiant D. Lifestyle Choices

1. Smoking a. Epidemiology i. Number one cause of preventable premature death in the United States ii. Percentage of the U.S. population that smokes: ~25%

iii. Males > females iv. There is a high rate of smoking in female teenagers b. Types of smoke i. Mainstream smoke (smoke inhaled by the smoker)

ii. Sidestream smoke (passive smoke inhalation)

c. Smoke contains over 4,000 components and over 40 known carcinogens i. Carbon monoxide ii. Arsenic iii. Formaldehyde iv. Hydrogen cyanide v. Nicotine (addictive component)

d. Cancers i. Lung (#1 cause of cancer death in the United States)

ii. Oral cavity, pharynx, and larynx iii. Esophagus and stomach

Note

Top 3 Causes of Death in Smokers

• Heart disease

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