Environmental Path

• Annual rate of occupational injuries: 7,400/100,000 workers.
• Annual fatality rate: 4.8/100,000 workers
• Highest rate areas: mining, agriculture, construction, transportation, and public utility industries

• EPA - regulates exposure to pesticides, toxic chemicals, water & air pollutants, and hazardous waste
• FDA - regulates drugs, med devices, food additives, and cosmetics
• OSHA - mandates that employers provide safe working conditions for employees
• Consumer Product Safety Commission - regulates all other products sold for use in homes, schools, or recreation

True.

• - CV disease
• - chronic resp disease
• - neoplasia (lung ca is the most common cause of cancer death in the US and throughout the world)

*note: tobacco use is risk factor also for: peptic ulcers, osteoporosis, and early menopause

• Synergy: smoking interacts w other environmental and occupational exposures in an additive or synergistic fashion
• ex: the increase in risk of lung ca in cigarette smokers exposed to asbestos

• 440,000 premature deaths
• 10 million cases of chronic disease
• Annual economic loss of $157 billion from health-related costs

• 43 known chemical carcinogens: NNK, NNN, polonium 210
• Carcinogenic metals: arsenic, cadmium, nickel, chromium
• Potential promoters: acetylaldehyde and phenol
• Irritants: nitrogen dioxide and formaldehyde
• Cilia toxins: hydrogen cyanide
• Others: CO and nicotine

• Nicotine is an alkaloid that readily crosses the blood-brain barrier and stimulates nicotine receptors in the brain
• Responsible for acute pharmacologic effects associated w tobacco use that are most likely mediated by catecholamines
• Increases HR, BP, coronary artery blood flow, contractility, CO, & mobilization of free fatty acids
• responsible for tobacco addiction

• Hypertension and hypercholesterolemia
• (Acute myocardial infarction & stroke: in women who take oral contraceptives)
• Contribute to cardiac arrest: increases platelet adhesion and aggregation, triggers arrhythmia, and causes an imbalance between demand for oxygen and supply to myocardium.
• Increased morbidity: acute resp infxns (influenza, acute & chronic sinusitis)

• 10 cigs a day can cause fetal hypoxia, as fetal carboxyhemoglobin levels are higher than maternal levels
• consequences: low birth weight, prematurity, increased incidence of spontaneous abortion, complications at delivery (premature rupture of membranes, placenta previa, and abruptio placentae)

• COPD
• Cardiovascular disease
• Cerebrovascular disease

• Solubility in water
• particle size and airway anatomy
• concentration and chemical reactivity
• host clearance mechanisms

• COPD
• - Emphysema & Chronic Bronchitis

• Reactive oxygen species "free radicals" from cigarette --> inactivation of antiproteases ("functiona;" alpha1AT deficiency) --> increase of neutrophil elastase. Elastase breaks down walls of alveoli, so you end up with lots of tissue damage (weakened and collapsed air sacs with excess mucus)
• - also contributing is alveolar macrophages, whose macrophase elastase and metalloproteinases increase as well
• - bullous emphysema usually found in upper lobes, with large subpleural bullae

• Lung
• Larynx
• Lip and oral cavity
• Esophagus
• Bladder
• Cervical
• Pancreas
• Stomach

• Carbon Monoxide
• It impairs release of oxygen from hemoglobin, so it decreases the delivery of oxygen to peripheral tissues
• CO also binds to other heme-containing proteins such as myoglobin and cytochrome oxidase

CO is an odorless, colorless byproduct of incomplete combustion of hydrocarbons

• Non-smoker: 0-2%
• Smoker: 5-6%
• Toxic: 15-40%: HA, dizzy, loss of motor control & lethargy
• Coma/Death: >40-50%

• Acute poisoning: cherry-red coloring of skin and mucus membranes caused by carboxyhemoglobin (incapable of carry O2, interferes w release of O2 from hemoglobin)
• Chronic poisoning: persistent low levels of CO cause chronic hypoxia, resulting in irreversible CNS changes

Non-neoplastic lung reaction to inhalation of mineral dust (coal, silica, asbestos, beryllium), organic and inorganic particulates, chemical vapors and fumes

• 1) amount of dust retained in the lung and airways
• 2) size, shape, and therefore bouyancy of the particles
• 3) particle solubility and physiochemical reactivity
• 4) possible additional effects of other irritants (eg, concomitant tobacco smoking)

• *the most dangerous particles range from 1-5 micrometers b/c they may reach the terminal small airways and air sacs and settling in the lining
• - smaller particles tend to cause acute lung injury
• - larger particles resist dissolution and so may persist within the lung parenchyma for years (tend to evoke fibrosing collagenous pneumoconioses, such as is characteristic of silicosis)

• 1) asymptomatic anthracosis: most innocuous coal-induced pulmonary lesion in coal miners and seen in all urban dwellers and tobacco smokers. Inhaled carbon pigment is engulfed by alveolar or interstitial machrophages, which then accumulate in the CT along the lymphatics (including pleural lymphatics), or in organized lymphoid tissue along the bronchi or in the lung hilus.
• 2) simple CWP: characterized by coal macules (1-2 mm in diameter) and then somewhat larger coal nodules. Coal macule consists of carbon-laden macrophages; nodule has collagen fibers. Upper lobes and upper zones of lower lobes are heavily involved. They're located next to resp bronchioles, the site of initital dust accumulation. Centrilobular emphysema: dilation of adjacent alveoli to affected resp broncioles
• 3) Complicated CWP (PMF): occurs on background of simple CWP and requires years to develop. Characterized by intensely blackened scars larger than 2cm, sometimes up to 10 cm in diameter. Usually multiple. Lesions consist of dense collagen and pigment, center is often necrotic (resulting from local ischemia).

• Progressive Massive Fibrosis
• a generic term that applies to a confluent, fibrosing reaction in the lung that could be a complication of any pneumoconiosis, although more common in CWP and silicosis
• leads to increasing pulmonary dysfunction, pulmonary hypertensio, and cor pulmonale (rt-sided heart failure)

coexistence of rheumatoid arthritis with pneumoconiosis

• A lung disease caused by inhalation of crystalline silicon dioxide (silica)
• Currently it's THE MOST PREVALENT CHRONIC OCCUPATIONAL DISEASE in the world
• presents after decades of exposure, as slowly progressing, nodular, fibrosing pneumoconiosis

• Crystalline form: quartz, crystobalite, and tridymite. Much more fibrogenic. Quartz is commonly implicated in silicosis.
• Amorphous form: talc, vermiculate, mica

• Increased susceptibility: Tuberculosis
• Other diseases: increased risk of lung ca, mycobacterial infxn, autoimmune disorders, airflow obstruction, chronic bronchitis

• silica particles cause activation & release of mediators by macrophages --> fibrogenic effect
• Acute silicosis: Characterized early on by tiny, barely palpable, discrete pale to blackened (if coal dust is present) nodules in upper zones of lungs.
• Advanced silicosis: As disease progresses, 1)nodules coalesce into hard, collagenous scars in upper lobes (some undergo central softening and cavitation due to superimposed TB or ischemia)--> progressive MASSIVE FIBROSIS
• 2) thin sheets of calcification occur in hilar LNs and seen radiographically as eggshell calcification
• 3) birefringent silica particles

• histologically: nodular lesions consist of concentric layers of hyalinized collagen surrounded by dense capsule of more condensed collagen
• peripheral zone is whorled and becomes less organized toward edges
• Outer zone contains macrophages, lymphocytes, and loosely formed collagen --> site of active enlargement and ongoing inflammation

• a family of crystalline hydrated silicates that form fibers
• serpentine: chrysotile (used in industry); curly & flexible fibers. Likely to become impacted in upper resp. passages and removed by mucociliary elevator. Once trapped in lungs, gradually leached from tissues b/c more soluble than amphiboles.
• amphibole: straight, stiff, brittle fibers; more pathogenic (able to reach deeper into lungs), particularly with respect to induction of malignant pleural tumors (mesotheliomas). Align themselves in airstream and thus are delievered deeper into lung, where they penetrate epithelial cells and reach the interstitium

• parenchymal interstitial fibrosis (asbestosis)
• bronchogenic carcinoma
• pleural effusion
• localized fibrotic plaques
• mesothelioma
• laryngeal carcinoma

• BOTH! Asbestos can act as a tumor initiator and a tumor promoter.
• One study of asbestos workers found fivefold increase of lung carcinoma for asbestos exposure alone, while asbestos exposure and smoking together led to a 55-fold increase in risk of lung ca.

• Starts in lower lobe (in contrast to CWP and silicosis), and progresses to middle and upper lobes
• pleural thickening
• scarring may result in pulmonary hypertension

• 5x risk of bronchogenic carcinoma (increased more if a smoker)
• 1000x risk of mesothelioma (not increased by smoking)

As golden brown, fusiform or beaded rods, with a translucent center and consist of asbestos fibers coated w an iron-containing proteinaceous material.

Asbestosis is marked by diffuse pulmonary interstitial fibrosis, which is indistinguishable from diffuse interstitial fibrosis resulting from other causes, except for the presence of asbestos bodies. The bodies arise when macrophages attempt to phagocytose asbestos fibers; the iron is presumably derived from phagocyte ferritin.

Pleural plaques; well-circumscribed plaques of dense collagen, often containing calcium. They develop most frequently on the anterior and posterolateral aspects of the parietal pleura and over the domes of the diaphragm.

• Used in industries like metal machining, ceramics, and nuclear weapons manufacturing
• *nuclear and aerospace industry*

Beryllium is an acute lung irritant and is associated w development of acute pneumonitis.

• Chronic exposure to beryllium can cause the development of hypersensitivity pneumonitis (in genetically sensitive ppl)
• Also is associated w development of Non-caseating granulomas in lungs, liver, kidneys, adrenal glands, and LNs

• hepatic necrosis
• - toxicity begins w nausea, vomitting, diarrhea, shock
• - w serious overdosage, liver failure ensues, with centrilobular necrosis
• - *some pts show renal and myocardial damage

2-4 gm fatal in children: resp alkalosis followed by metabolic acidosis

• 3 gm or more daily (the dose required to treat chronic inflammatory conditions)
• HA, dizzy, tinnitus, hearing difficulty, mental confusion, drowsiness, nausea, vomiting, and diarrhea
• CNS changes may progress to convulsions and coma
• can have gastric ulceration (GI bleeding too --> aspirin acetylates platelet COX and blocks ability to make thromboxane A2, an activator of platelet aggregation)

• Ethanol is metabolized to acetaldehyde by alcohol dehydrogenase in gastric mucosa and liver.
• Women have lower gastric levels of alcohol dehydrogenase. Also an ethnic variability
• Acetaldehyde is converted to acetic acid by aldehyde dehydrogenase.
• - oxidation by ADH (alcohol denhydrogenase) takes place in cytosol & catalase (hydrogen peroxide to water) is located in peroxisomes
• - oxidation of acetaldehyde by aldehyde dehydrogenase occurs in mitochondria

50% of Vietnamese, Chinese, and Japanese people

Women have lower gastric levels of alcohol dehydrogenase activity.

• CNS: ataxia, stupor, coma, resp arrest and death
• Stomach: acute gastritis
• Liver: acute alcoholic hepatitis, from minimal disease to fulminant hepatic failure, fatty change, and cirrhosis

• reversible manifestation
• can produce fever, liver tenderness, and jaundice
• ethanol is toxic to hepatocytes
• malaise, anorexia, tender hepatomegaly, 10-20% risk of death
• histology: hepatocyte swelling and necrosis, Mallory bodies, neutrophils, fibrosis, steatosis

Hard, shrunken liver with formation of micronodules of regenerating hepatocytes surrounded by dense bands of collagen.

• Wernicke syndrome: caused by thiamine deficiency; ataxia, disturbed cognition, opthalmoplegia, and nystagmus. REVERSIBLE
• Korsakoff syndrome: toxicity and thiamine deficiency; severe memory loss. IRREVERSIBLE
• Cerebellar degeneration: nutritional deficiency
• Peripheral neuropathy: thiamine deficiency

• testicular atrophy
• spontaneous abortions
• FAS (growth restriction, mental retardation, birth defects, microcephaly, facial dysmorphology, malformations of CV system, GI system abnormalities)

• Metabolite, acetaldehyde, may act as tumor promoter
• inhibits detox of chemical carcinogens
• Synergy w Hep B & C to develop hepatocellular carcinoma
• Increased incidence of carcinoma in oral cavity, pharynx, esophagus, and liver

• Initially a large, fatty liver (reversible)
• In late stages, becomes small, non-fatty, and firm
• End stage: nodular cirrhosis (irreversible)

• Portal hypertension: ascites, esophageal varices, splenomegaly, spider nevi, caput medusase
• Hepatic failure: bleeding disorders, jaundice, edema, encephalopathy, and immune suppression

• Actue effects: disordered sensory perception, impaired motor coordination, increased heart rate and BP for 4-5 hrs
• Chronic effects: similar to smoking tobacco, but 3x more tar
• Beneficial effects: decreased intraocular pressure, antiemetic

• comes from a coca plant
• inhibits reuptake of NT dopamine and norepi by presynaptic neurons, resulting in excessive stimulation of post-synaptic cells
• disrupts normal ion transport in myocardium
• toxic effects are NOT dose-related

• HTN
• tachycardia
• arrhythmia
• myocardial infarction (promotes vasoconstriction) or acquired long QT interval
• cerebral infarction (due to cardiac arrhythmias and ischemia)
• rhabdomyolysis
• placental abruption (decreased blood flow to fetus causes fetal hypoxia)

• nasal septum perforation
• decreased lung capacity
• dilated cardiomyopathy

• Poppy plant, closely related to morphine
• often diluted with talc or quinine
• IV or SQ injection
• Effects: euphoria, hallucinations, somnolence

• skin and subcutaneous tissue
• heart valves
• liver
• lungs

• Endocarditis --> involves right sided heart valves, particularly the tricuspid
• Most cases are caused by Staph aureus

• sudden death (resp depression or arrhythmias)
• pulmonary edema, embolism, granulomas, and abscesses
• infectious complications: endocarditis, hepatitis, HIV
• cutaneous lesions: thrombosed veins and scars
• renal diseases: amyloidosis, focal glomerulosclerosis

• High affinity for sulfhydryl groups
• Competition with calcium ions
• Inhibition of membrane-associated enzymes
• Impaired production of 1,25-dihydroxyvitamin D

urban air, dirt, food, paint dust

• No, it's directly absorbed, distributed, and excreted
• - absorption depends upon the route of exposure and the age and nutritional status of the exposed person
• lead inhaled into lower resp tract is absorbed completely
• children absorb a greater proportion of lead from the GI tract than do adults
• fasting, iron deficiency, zinc deficiency, and calcium deficiency may increase GI absorption of lead

• 85% in bone and teeth (30 yr half life)
• 10% in blood, anemia (clears rapidly, so detection indicates only recent exposure)
• brain, peripheral nerves, gingival, kidney, GI tract

• Early sx: fatigue, HA, irritability, metallic taste, uneasy stomach, poor appetite, weight loss, reproductive problem
• Late sx: memory problems, nausea, kidney problems, weight loss, constipation, weak wrists & ankles

• Lead interferes w heme biosynthesis (high affinity for sulfhydryl group), so it causes a microcytic hypochromatic anemia --> punctate basophilic stippling of erythocytes is characteristic
• Competition w Ca2+ --> interferes w nerve transmission and brain development
• Inhibition of membrane-associated enzymes --> decreased survival of RBCs (hemolysis), renal damage, and HTN
• Impairs production of 1,25-dihydroxyvitamin D

• Lead poisoning is diagnosed when BLL is greater than 10 mcg/dl on a venous blood sample (indicates RECENT exposure only)
• Chronic exposure can be elevated by testing for elevated blood erythrocyte protoporphyrin (EP) or zinc protoporphyrin (ZPP) concentrations (greater than 35 mcg/dL)
• Detection of gamma-aminolevulinic acid levels in urine

• Electrical
• Ionizing radiation
• Trauma
• Thermal

• Low voltage: 120v or 240v in home wiring
• High voltage: lightning, high-power lines
• Injuries:
• Burns (at site of entry/exit and internal organs)
• V-fib, electrical/mechanical dissociation
• *severity related to amount of current

• Natural: cosmic radiation, radon gas
• Artificial sources: x-rays and radiotherapy
• Two forms: 1) electromagnetic (x-rays and gamma rays), 2) high-energy particles (alpha, beta, and proton)
• - damages DNA either directly or indirectly through generation of free-radicals

• Tissues w high turnover and extremely vulnerable (bone marrow, GI tract, germ cells, squamous epithelium, endothelial cells, lymphocytes)
• Tissues w slow turnover are slowly depopulated
• Factors related to damage:
• - rate of dose delivery
• - cellular repair mechanisms
• - oxygen (oxygen amplifies radiation damage through generation of free-radicals)

Fibrosis. At low doses used for cancer, replacement of normal parenchymal tissue by fibrosis, resulting in scarring and loss of function. May be secondary to ischemic injury caused by vascular damage, death of parenchymal cells, or deletion of stem cells.

• unintentional injuries, including MVAs
• homicide
• suicide
• leading cause of death for adolescents and adults up to age 44 in US
• - Mechanical force: may inflict soft-tissue, bone, and head injuries

• abrasion: removal of surface layers by friction
• contusion: rupture of small blood vessels with extravasation of blood into tissues
• laceration: ragged tear in tissue
• incision: sharp penetrating object

• coup = injury to the brain occurring directly beneath the area of impact
• counter-coup = injury to opposite side of brain; occurs when force impacting the head causes the brain to slam to the opposite side of the skull, shearing brain cells
• often seen in MVAs

• depth of burn
• % of body surface involved
• possible internal injuries from inhalation of hot and toxic fumes
• promptness/efficacy of therapy

• 1st degree: focal necrosis of epidermis (epithelial involvement only)
• 2nd degree: necrosis extending to upper dermis, skin appendages spared (both dermis and superficial dermis)
• 3rd degree: necrosis extending into deep dermis (full thickness), skin appendages destroyed, loss of sensation due to nerve damage (sub-cutaneous may be involved)

• Partial thickness burn: at least the deeper portions of dermal appendages are spared; 1st and 2nd degree. Appear pink or mottled with blisters and are painful.
• Full thickness burn: total destruction of the epidermis and dermis, with loss of the dermal appendages (provide cells for epithelial regeneration); 3rd degree. Appear white or charred, dry, and anesthetic (due to nerve ending destruction)

• burns >50% of BSA potentially fatal
• >20% of BSA hypovolemic shock
• Secondary infection - Pseudomonas aeruginosa, staph, candida
• sepsis --> MSOF --> death
• treatment: debridement