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What are the regulatory agencies?
- Environmental Protection Agency - regulates exposure to pesticides, toxic chemicals, water and air pollutants, and hazardous wastes
- Food and Drug Administration - drugs, medical devices, food additives, cosmetics
- Occupational Safety and Health Administration - safe environment for workers
- Consumer Product Safety Commision - regulates all other products sold
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Tobacco use is a risk factor for what?
- cardiovascular disease
- neoplasia
- chronic respiratory disease, peptic ulcers, osteoporosis, early menopause
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What is tobacco use in synergy with?
smoking interacts with other enviornmental and occupational exposures in an additive or synergist fashion
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What is the charac of carbon monoxide?
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How is carbon monoxide made?
incomplete combustion of hydrocarbons
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What makes carbon monoxide so dangerous?
- it has 200-fold higher affinity for hemoglobin than oxygen
- less oxygen delivered to tissue
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What are the % saturation by CO for non-smoker, smoker, toxic, coma/death?
- non smoker - 0-2%
- smoker - 5-6%
- toxic - 15-40%
- coma,death - more than 40-50%
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Describe the symptoms of acute carbon monoxide poisoning.
- cherry-red coloring of skin and mucus membranes caused by carboxy-hemoglobin
- they are incapable of carrying oxygen
- interferes with release of oxygen from oxyhemoglobin
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Describe the symptoms for chronic poinsoning.
persistent low levels of CO cause chronic hypoxia resulting in irreversible CNS changes
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What is pneumoconioses?
non-neoplastic lung rxn to inhalation of mineral dust, organic, and inorganic particulates, chemical vapors and fumes
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Development of a pneumoconiosis depends on what 4 things?
- 1. the maount of dust retained in the lung and airways
- 2. the size, shape, and therefore buoyancy of particles
- 3. particle solubility and physiochemical reactivity
- 4. the possible additional effects of other irritants
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What is the most dangerous size of particles and why?
- most dangerous particles = 1-5 micrometer in diameter
- because they may reach the terminal small airways and air sacs and settle in their linings
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Which type of particles is more likely to appear in pulmonary fluids and reach toxic levels rapidly?
smaller particles
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What does smaller particles cause?
tend to cause acute lung inury
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What does larger particles tend to cause and why?
- resist dissolution and so may persist w/in the lung parenchym for years
- leads to fibrosing collagenous penumoconioses (charac of silicosis)
- larger particles -> fibrosis/collagenous
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what are some examples of mineral dusts?
- coal -> focal dust emphysema
- silica -> silicotic nodule
- asbestos -> abestosis
- beryllium
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what is anthracosis?
- most innocuous coalinduced pulmonary lesion in cola miners
- can be seen in all urban dwellers and tobacco smokers
- inahled carbon pigment is enfulfed by alveolar or interstitial macrophages, which then accumulate in the CT along lymphatics, including the pleural lymphatics, or in organized lymphoid tissue along the bronchi or in lung hilus
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What are the four types of Coal Worker's pneumonconiosis?
- 1. asymptomatic anthracosis
- 2. Simple coal worker's pneumoconiosis (CWP)
- 3. Complicated CWP or Progressive Massive Fibrosis(PMF)
- 4. Caplan's Syndrome
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Describe the Coal Worker's Pneumoconiosis (CWP).
- benign disease that causes little decrement in lung function
- in mild forms of complicated CWP fail to show abnormalities of lung function
- minority of cases, PMF (progressive massive fibrosis) develops, leading to increasing pulmonary dysufnction, pulmonary hypertension, and cor pulmonale (right sided heart failure)
- once PMF develops, can be progressie even if further exposure to dust is prevented
- some evidence show that exposure to coal dust increases the incidence of chronic bronchitis and emphysema
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What is the characterisit of simple CWP? What is it made out of? Where in the lungs would it mostly be affected?
- charac - coal macules (1-2 millimeter in diameter)
- macules consists of carbon-laden macrophages and small network of collagen fibers
- mostly involve the upper lobes and upper zones of lower lobes
- located pirmarily adjacent to respiratory bronchioles, site of initial dust accumulation
- -> dilation of adjacent alveoli = centrilobular emphysema
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What is complicated CWP (PMF)? How does it develop? Characterization? Composition of lesion?
- many years to develop from CWP
- charac - intensely blackened scars larger than 2cm-10cm, multiple
- composition of lesion - desnse collagen and pigment, center is necrotic
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What is Caplan's syndrome?
- unique form
- characterized by coexistence of rheumatoid arthritis with pneumoconiosis
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What is silicosis?
- lung disease caused by inhalation of crystalline silicon dioxide (silica)
- is the nost prevalent chronic occupational disease in the world
- presents after decades of exposure as a slowly progressing, nodular, fibrosing pneumoconiosis
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What are the 2 forms that silica come in? which one is more fibrogenic?
- crystalline form - quartz, crystobalite = most active form and most fibrogenic
- amorphous form - talc, vermiculate, mica
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What is the detection method of silicosis and what is seen?
- Detected when routine chest radiography
- show fine nodularity in upper zones of the lung with normal pulmonary functions
- slow to kill
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Silicosis is aossicated with an increased susceptibility to _____.
tuberculosis
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Characterization of silicosis.
- tiny, barely palpable, discrete pale to blakened nodules in the upper zones of the lungs
- nodules may coalesce into hard, ollagenous scars
- some undergo central softening and cavitation
- calcification occur in lymph nodes seen radiographically as eggshell calcification
- histologicaly, nodular lesions consist of concentric layers of hyalinized collagen surrounded by a dense capsule of more condensed collagen
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what is the pathophysiology of disease for silicosis?
- silica particles causes activation and release of mediators by macrophages
- fibrogenic effect
- presents after edecades of exposure
- upper zones of lungs
- early -> tiny pale/blackened nodules
- progression -> hard, collagenous scars -> progressive massive fibrosis
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Advanced silicosis has what charac?
- hard collagenous scars starting in upper lobes
- fibrotic hilar lymph nodes w/ "egg-shell calcifications"
- birefringent silica particles
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What is asbestos?
crystalline hydrated silicates that form fibers
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what dictate where asbestos cause disease?
- concentration
- size
- shape
- solubility of different forms
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what are the 2 distinct geometric forms of asbestos?
- serpentine (curly and flexible fibers) - ex. chrysotile = most of asbestos used in industry
- amphibole (straight, stiff, and brittle fibers) - more pathogenic even though less prevalent
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how does the chrysotiles form of asbestos can cause disease?
- more flexible, curled structure are likely to become impacted in upper respiratory passages and removed by mucociliary elevator
- once trapped in lungs, chrysotiels are gradually leached from the tissues since they are more soluble
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how does the amphiboles form of asbestos cause disease?
- straight, stiff amphiboles may align hemselves in airstream and thus be delivered deeper into the lungs
- then they can penetrate epithelial cells and reach the interstitium
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what makes asbestos different than other inorganic dusts?
- asbestos can act as a tumor initiator and a tumor promoter
- 5-fold increase of lung carcinoma for asbestos along
- 55-fold increase - asbestos and smoking
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What is the progresion of asbestosis?
- starts in lower lobe and progresses to middle and upper lobes
- pleural thickening
- scarring may result in pulmonary hypertension
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What is the first manifestation of asbestosis? what happens after that?
- first is dyspnea (with sputum at later stage)
- shows rarely after 10 years, more common after 20 yrs
- may remain static or progress to respiratory failure, cor pulmonale, and death
- chest films show irrregular linear densities,
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Asbestos is marked by diffuse pulmonary intersitital fibrosis, which is indistinguishable from diffuse intersitital fibrosis, except for the presence of what?
- Presence of asbestos bodies.
- asbestos bodies appear as golden brown, fusiform or beaded rods with a translucent center and consist of asbestos fibers coated with an iron-containing proteinaceous material
- arise when marcrophages attempto to phagocytize asbestos fibers; the iron is dertived from phagocyte ferritin
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Asbestosis begins as fibrosis around where?
- around respiratory bronchioles and alveolar ducts
- extends to adjacent alveolar sac and alveoli
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Fibrous tissue distorts the native architecture through doing what?
creating enlarged airspaces enclosed w/in thick fibrous walls -> honeycombed
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For asbestosis, there is how many times risk of bronchogenic carcinoma?
- 5x risk
- increased more if a smoker
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for asbestosis, how much risk is of mesothelioma?
- 1000x
- not increased by smoking
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What are the types of beryllium?
- metallic beryllium
- its oxides, alloys or salts
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How is beryllium used in industry?
- metal machining
- ceramics
- nuclear weapons manufacturing
- estimated number of 134,000-800,000 current and former worker in US
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For berylliosis, you have a normal chest x-ray. What are the type of berylliosis?
- acute pneumonitis
- chronic berylliosis
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Describe chronic berylliosis. Found in who? How is it found in organs?
- who - genetically susceptible individuals (delayed sensitivity)
- how - non-caseating granulomas in lungs, liver, kidneys, adrenals and lymph nodes
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What are the therapeutic drugs that can be toxic?
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Large dose (how much?) can cause what? end in what?
- dose - 5-25 gm
- cause hepatic necrosis
- occasionally causes renal and myocardial damage
- may end in liver failure requiring transplantation
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how much aspirin is fatal in children?
2-4gm: respiratory alkalosis followed by metabolic acidosis
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Chronic toxicity of aspirin is how much? Can cause what?
- dose - more than 3 gm per day
- headache, tinnitus, vomitting, diarrhea, mental confusion, erosive gastritis, renal papillary necrosis
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What is the conversion of alcohol?
- ethanol ----->acetaldehyde by alcohol dehydrogenase
- acetaldehyde --------> acetic acid by aldehyde dehydrogenase
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Who has lower gastric levels of alcohol dehyrogenase?
women
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What are the symptoms of acute alcoholism?
- ataxia
- stupor = near unconscious
- coma
- respiratory arrest
- death
- for stomach - acute gastritis
- for liver - acute alcoholic hepatitis, malaise, anorexia, tender hepatomegaly, 10-20% risk of death
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what is histology for acute alcoholism in liver?
hepatocyte swelling and necrosis, mallory bodies, neutrophils, steatosis, fibrosis
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For chronic alcoholism, what syndrome or disorder can be seen?
- Wernicke syndrome
- Korsakoff syndrome
- Cerebellar degeneration
- peripheral neuropathy
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What is the symptoms seen with Wernicke syndrome?
- ataxia
- disturbed cognition
- opthalmoplegia
- nystagmus - rapid involuntary movement of eyes
- REVERSIBLE
- caused by thiamine deficiency
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What are the symptoms for Korsakoff syndrome? Reversible? Caused by?
- severe memory loss
- IRREVERSIBLE
- toxicity and thiamine deficiency
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ethanol is metabolized by alcohol dehydrogenase and by what else?
cytochrome P-450 and catalase in liver
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Who has reduced activity of alcohol dehydrogenase due to a point mutation?
50% of Chinese, Vietnamese, and Japanese
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In liver, what can ethanol cause?
ethanol can cause fatty change, acute alcoholic hepatitis, and cirrhosis
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With chronic ethanol use, irreversible liver damage is produced called alcoholic cirrhosis. what is the characteristics?
- hard, shrunken liver
- micronodules of regenerating haptocytes surrounded by dense bands of collagens
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Chronic alcoholism affects the nervous system and causes 2 syndromes. what are the characteristics?
- chronic thiamine deficiency -> Wernicke syndrome - ataxia, disturbed cognition and is REVERSIBLE
- Korsakoff syndrome - severe memory loss and IRREVERSIBLE
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Chronic alcoholism can affect GI tract and Reproductive system how?
- GI tract - gastritis
- repoductive system - testicle atrophy and spontaneous abortion
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What is the characteristics of fetal alcohol syndrome?
- microcephaly
- facial dysmorphology
- malformations of brain, cardiovascular system and genitourinary system
- infants show - growth retardation, microcephaly, atrial septal defect, short palpebral fissures, maxillary hypoplasia
- {growth retardation, mental retardation, birth defects}
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Relationship between ethanol and cancer?
- heavy alcohol use synergizes with chronic Hep B and Hep C infeciton in predisposing to the development of hepatocellular carcinoma
- acetaldehyde may act as a tumor promoter
- inhibits detoxification of chemical carcinogens
- increase incidence of carcinoma - liver, oral cavity, esophagus, pharynx
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