Environmental Path

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Environmental Path
2011-02-28 15:03:27
Pathology Tyler

Environmental Path - Tyler
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  1. What is the annual rate of occupational injuries in the US? Annual fatality rate? In what areas of work are the highest fatality rates seen?
    • 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
  2. Name some occupational regulatory agencies and what they do.
    • 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
  3. T/F: Use of tobacco products is associated w more mortality AND morbidity than any other personal, environmental, or occupational exposure.
  4. What 3 diseases account for most of the deaths related to smoking?
    • - 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
  5. How does "synergy" relate to tobacco use?
    • 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
  6. How many premature deaths per year in US due to smoking? How many cases of chronic disease? Annual economic loss from health-related costs?
    • 440,000 premature deaths
    • 10 million cases of chronic disease
    • Annual economic loss of $157 billion from health-related costs
  7. Of the 4000 constituents in cigarette smoke, how many are known chemical carcinogens? Examples? What are some cacinogenic metals? Irriatants and cilia toxins? Others?
    • 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
  8. Describe the biochemical effects of nicotine in the body.
    • 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
  9. Smoking is a multiplicative risk factor for many diseases, including Cardiovascular disease. What risk factors apply here? What two diseases does this contribute to the development of?
    • 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. What are some consequences of maternal smoking on the fetus?
    • 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)
  11. Name some non-neoplastic diseases associated w smoking
    • COPD
    • Cardiovascular disease
    • Cerebrovascular disease
  12. What are some factors determining lung injury?
    • Solubility in water
    • particle size and airway anatomy
    • concentration and chemical reactivity
    • host clearance mechanisms
  13. What is the #4 cause of morbidity and mortality in US? What 2 other diseases are associated w this disease?
    • COPD
    • - Emphysema & Chronic Bronchitis
  14. Describe the pathology of emphysema. Where is bullous emphysema usually found?
    • 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
  15. What are some neoplasias caused by smoking?
    • Lung
    • Larynx
    • Lip and oral cavity
    • Esophagus
    • Bladder
    • Cervical
    • Pancreas
    • Stomach
  16. What chemical has a 200x higher affinity for hemoglobin than oxygen? What does it impair? To what other molecules does it bind?
    • 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
  17. What is CO a byproduct of?
    CO is an odorless, colorless byproduct of incomplete combustion of hydrocarbons
  18. What are CO saturation % for non-smokers, smokers, toxic levels, and coma/death level?
    • Non-smoker: 0-2%
    • Smoker: 5-6%
    • Toxic: 15-40%: HA, dizzy, loss of motor control & lethargy
    • Coma/Death: >40-50%
  19. What are some symptoms of acute CO poisoning, as compared to chronic poisoning?
    • 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
  20. What is a pneumoconioses?
    Non-neoplastic lung reaction to inhalation of mineral dust (coal, silica, asbestos, beryllium), organic and inorganic particulates, chemical vapors and fumes
  21. What 4 conditions does the development of pneuconiosis depend?
    • 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)
  22. How does particulate size effect the resulting injuries of pneumoconiosis?
    • *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)
  23. What is the spectrum of lung findings in coal workers? Describe these stages.
    • 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).
  24. What is PMF?
    • 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)
  25. What is Caplan Syndrome?
    coexistence of rheumatoid arthritis with pneumoconiosis
  26. What is silicosis?
    • A lung disease caused by inhalation of crystalline silicon dioxide (silica)
    • presents after decades of exposure, as slowly progressing, nodular, fibrosing pneumoconiosis
  27. Silicosis can present in crystalline and amorphous forms. Describe these forms.
    • Crystalline form: quartz, crystobalite, and tridymite. Much more fibrogenic. Quartz is commonly implicated in silicosis.
    • Amorphous form: talc, vermiculate, mica
  28. What disease is silicosis associated with an increased susceptibility to? What other diseases is it generally associated with?
    • Increased susceptibility: Tuberculosis
    • Other diseases: increased risk of lung ca, mycobacterial infxn, autoimmune disorders, airflow obstruction, chronic bronchitis
  29. Describe the pathophysiology of silicosis
    • 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
  30. Describe the histological appearance of silicosis
    • 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
  31. What is asbestos? What are the 2 distinct geometric shapes?
    • 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
  32. To what diseases is asbestosis linked?
    • parenchymal interstitial fibrosis (asbestosis)
    • bronchogenic carcinoma
    • pleural effusion
    • localized fibrotic plaques
    • mesothelioma
    • laryngeal carcinoma
  33. Is asbestos a tumor initiator or a tumor promoter?
    • 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.
  34. Describe asbestosis morphology
    • 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
  35. Being an asbestos worker gives you 5x the risk of developing this disease? and 1000x risk of this disease? How are these 2 diseases affected by smoking?
    • 5x risk of bronchogenic carcinoma (increased more if a smoker)
    • 1000x risk of mesothelioma (not increased by smoking)
  36. How do asbestos bodies appear ?
    As golden brown, fusiform or beaded rods, with a translucent center and consist of asbestos fibers coated w an iron-containing proteinaceous material.
  37. Asbestosis is marked by what initially? What distinguishes it from diffuse interstitial fibrosis?
    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.
  38. What are the most common manifestation of asbestos exposure? Where do these develop?
    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.
  39. What industries use beryllium?
    • Used in industries like metal machining, ceramics, and nuclear weapons manufacturing
    • *nuclear and aerospace industry*
  40. What is berylliosis?
    Beryllium is an acute lung irritant and is associated w development of acute pneumonitis.
  41. Describe the features of chronic berylliosis.
    • 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
  42. When taken in large doses (5-25 gm), acetaminophen causes...
    • 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
  43. What dose of acetylsalicylic acid (aspirin) is fatal for children? Signs and symptoms?
    2-4 gm fatal in children: resp alkalosis followed by metabolic acidosis
  44. At what dosage could chronic toxicity form aspirin take place? Symptoms?
    • 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)
  45. How is ethanol metabolized in body?
    • 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
  46. Which ethnicities have reduced activity of alcohol dehydrogenase due to a point mutation?
    50% of Vietnamese, Chinese, and Japanese people
  47. Why can women handle less booze than men?
    Women have lower gastric levels of alcohol dehydrogenase activity.
  48. What are the organ effects of acute ethanol abuse?
    • 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
  49. Describe "acute alcoholic hepatitis" in the liver, due to acute alcoholism.
    • 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
  50. With chronic alcohol use, 10-15% of alcoholics develop irreversible liver damage, or alcoholic cirrhosis. What is this disease characterized by?
    Hard, shrunken liver with formation of micronodules of regenerating hepatocytes surrounded by dense bands of collagen.
  51. Describe the effects of chronic alcoholism on the nervous system.
    • 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
  52. Chronic alcoholism effects on reproductive system?
    • testicular atrophy
    • spontaneous abortions
    • FAS (growth restriction, mental retardation, birth defects, microcephaly, facial dysmorphology, malformations of CV system, GI system abnormalities)
  53. What is chronic alcoholism's relationship with cancer?
    • 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
  54. Describe the signs and symptoms of liver cirrhosis.
    • Initially a large, fatty liver (reversible)
    • In late stages, becomes small, non-fatty, and firm
    • End stage: nodular cirrhosis (irreversible)
  55. What's the "stigmata" associated with liver cirrhosis?
    • Portal hypertension: ascites, esophageal varices, splenomegaly, spider nevi, caput medusase
    • Hepatic failure: bleeding disorders, jaundice, edema, encephalopathy, and immune suppression
  56. Marijuana (aka: THC) is absorbed 50% by smoking and 5-10% by ingestion. What are some acute and chronic effects of this crowd pleaser?
    • 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
  57. How does cocaine work on the body?
    • 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
  58. What are some acute toxic effects of cocaine?
    • 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)
  59. What are some chronic effects of cocaine?
    • nasal septum perforation
    • decreased lung capacity
    • dilated cardiomyopathy
  60. From where does heroin come, how is it administered to the body, and what are some effects?
    • Poppy plant, closely related to morphine
    • often diluted with talc or quinine
    • IV or SQ injection
    • Effects: euphoria, hallucinations, somnolence
  61. What 4 sites are most commonly affected with heroin use?
    • skin and subcutaneous tissue
    • heart valves
    • liver
    • lungs
  62. What's the most serious infection with heroin use?
    • Endocarditis --> involves right sided heart valves, particularly the tricuspid
    • Most cases are caused by Staph aureus
  63. Name some complications from heroin.
    • 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
  64. The toxicity of lead is related to multiple biochemical factors. Name 4 of these.
    • High affinity for sulfhydryl groups
    • Competition with calcium ions
    • Inhibition of membrane-associated enzymes
    • Impaired production of 1,25-dihydroxyvitamin D
  65. What are some sources for lead (poisoning)?
    urban air, dirt, food, paint dust
  66. Is inorganic lead metabolized?
    • 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
  67. Describe accumulation of lead in the body.
    • 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
  68. What are some early and late symptoms of lead poisoning?
    • 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
  69. What is the mechanism of toxicity in lead poisoning?
    • 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
  70. What are some diagnostic tools useful for indicating lead poisoning?
    • 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
  71. What are some physical agents that could lead to environmental pathology?
    • Electrical
    • Ionizing radiation
    • Trauma
    • Thermal
  72. Electrical injury has causes from low voltage or high voltage. Describe these differences and the possible injuries that may occur.
    • 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
  73. What are some sources of ionizing radiation? What are the two different forms?
    • 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
  74. What are some effects of radiation on the body?
    • 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)
  75. What is an important delayed complication of ionizing radiation?
    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.
  76. What does "trauma" consist of?
    • 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
  77. What's the difference between abrasion, contusion, laceration, & incision?
    • 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
  78. In reference to trauma & sudden acceleration/deceleration, what's a coup or counter-coup brain injury?
    • 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
  79. Burns cause 5000 deaths/yr with hospitalization of more than 10x that many persons. What does the clinical significance of burns depend upon?
    • depth of burn
    • % of body surface involved
    • possible internal injuries from inhalation of hot and toxic fumes
    • promptness/efficacy of therapy
  80. Describe the various degrees of thermal burns
    • 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)
  81. Difference between "partial thickness burn" and "full thickness burn"?
    • 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)
  82. What are some secondary issues due to thermal injuries?
    • burns >50% of BSA potentially fatal
    • >20% of BSA hypovolemic shock
    • Secondary infection - Pseudomonas aeruginosa, staph, candida
    • sepsis --> MSOF --> death
    • treatment: debridement