Flashcards in Ch 9 Deck (49)
What is GBD?
global disease burden: estimates burden imposed by environmental disease, including those caused by communicable and nutritional disease
what is the leading cause of health loss globally?
what is the leading cause of death in developed countries?
ischemic heart disease and cerebral vascular disease
what are the three conditions that 50% of childhood deaths are linked to?
pneumonia, diarrheal disease, malaria
what are the changing trends in disease from 1990-2010?
1. cardiovascular and circulatory disease
3. diarrhea, lower respiratory infection, other common infections
4. HIV/AIDS, tuberculosis
5. neonatal conditions
what stands to become the preeminent global cause of environmental disease in the 21st century?
what are the possible negative impacts?
increased incidence of:
-CV, cerebrovascular and respiratory diseases
- gastroenteritis, cholera, other foodborn/waterborn illnesses
- vector-born infectious diseases
what are xenobiotics?
exogenous chemicals in environment that may be absorbed into the body through the basement membrane
note: most solvents/drugs/xenobiotics are metabolized to inactive water-soluble product (detoxification) or activated to form toxic metabolites
where is cytochrome P-450 located?
what does it do?
primarily in ER or liver, also present in lungs, GI mucosa, other organs
is catalyzed rxns that either detoxify xenobiotics, or less commonly converts xenobiotics into active compounds that cause cellular injury
note: both rxns may produce ROS as byproduct, which cause cellular damage
what effect can fasting and starvation have on CYP activity?
they can both decrease activity
air pollution is especially hazardous to whom?
people with preexisting pulmonary or cardiac disease
what are the populations at risk? and the effects?
healthy adults and children: decreased lung function, increased airway reactivity, lung inflammation
athletes, outdoor workers, asthmatics: decreased exercise capacity increased hospitalizations
what are the populations at risk? and the effects?
healthy adults: increased respiratory symptoms
individuals with chronic lung disease: increased mortality
asthmatics: increased hospitalizations, decreased lung function
what effect does ozone have on the body?
free radicals injure the respiratory tract epithelial cells and type I alveolar cells, by releasing inflammatory mediators
mild symptoms: decreased lung function and chest discomfort
what effect does sulfur dioxide have on the body?
- combines with ozone and particulate matter -> witches brew
- is produced by power plants burning fossil fuels, copper smelting, byproduct of paper mills
- sulfuric acid and sulfuric trioxide: burning sensation in nose and throat, difficulty breathing, asthma attacks in those susceptible
what effect does particulate matter (soot) have on the body?
- soot causes pulmonary inflammation and secondary CV effects
- fine or ultrafine particles less than 10um in diameter are the most harmful! they are readily inhaled into the alveoli, releasing a number of inflammatory mediators
how is ozone produced?
interaction of UV radiations and O2 in the stratosphere, naturally accumulates in the ozone layer
how do acute and chronic CO poisoning occur?
chronic poisoning: working in tunnels, underground garages, highway toll booths with high exposure to automobile fumes
acute toxicity: small, closed garages, average car can produce sufficient CO to induce coma or death in 5 minutes
note: HB has 200-fold higher affinity for CO than oxygen
what effect does carbon monoxide have on the body?
CO kills by inducing CNS depression, widespread ischemic changes
- basal ganglia and lenticular nuclei
- if pt recovers, impaired memory, vision, hearing and speech
- generalized cherry-red color of the skin and mucous membranes***
signs of first few hours of CO poisoning vs 24-48 hours
first few hours brain is swollen, congested and cherry red
after 24-48 hours of survival, scattered petechial hemorrhages may be see in white matter with larger hemorrhages in the pellucidum
what are the most common causes of indoor air pollution?
wood smoke (polycyclic hydrocarbons=carcinogens), bioaerosis (Legionnaires disease, viral pnu, pet dander, fungal molds), radon (lung cancer), formaldehyde (building materials, poor ventilation)
what is the danger of lead?
it is readily absorbed, and binds to sulfhydryl groups in proteins and interferes with calcium metabolism
leads to hematologic, skeletal neurologic, GI and renal toxicity
where is most of the absorbed lead incorporated in the body?
bone and developing teeth, competes with calcium, half life in bone is 20-30 years!
what are the effects of lead poisoning in children?
- sensory, motor, intellectual and psychologic impairments including decreased IQ, retarded psychomotor dvlpment, blindness, radiodense deposits in epiphyses
- severe cases: psychoses, seizures, coma
note: lead toxicity in mother may impair brain development in prenatal infant
what are the effects of lead poisoning in adults?
- peripheral neuropathies: extensor muscles of the wrist and fingers often first (wrist-drop), followed by paralysis of peroneal muscles (foot-drop)
- headache, memory loss, anemia, red cell basophilic stipping
- lead lines: radiodense deposits in metaphyses, also in the gums
- lead colic: extremely severe, poorly localized abdominal pain
what are the effects of low-level lead toxicity?
subtle defects in intellect, behavioral problems, hyperactivity, poor organizational skills
what is the effect of mercury toxicity?
- mercury binds sulfhydryl groups, damages CNS and kidney
- main sources: contaminated fish, mercury vapors from metallic mercury in dental fillings
note: developing brain is extremely sensitive to methyl mercury
what are symptoms of Minamata disease?
cerebral palsy, deafness, blindness, mental retardation, major CNS defects in children exposed in utero
disasters caused by release of contaminated fish from industrial sources in Minamata bay in Japan
what does arsenic toxicity do?
interferes with cellular metabolism -> toxicities most prominent in GI tract, nervous system, skin and heart
large quantities: GI, CV, CNS
chronic skin changes: hyperpigmentation, hyperkeratosis
what symptoms present 2-8 weeks post arsenic exposure?
sensorimotor neuropathy, paresthesias, numbness, pain
what does cadmium toxicity lead to?
preferentially toxic to kidneys and lungs (uncertain mechanisms, may involve increased ROS)
- obstructive lung disease, renal tubular damage, skeletal abnormalities assoc with calcium loss
- "itai-itai" (ouch-ouch in Japanese): osteoporosis and osteomalacia with renal disease
list the toxins that cause lung cancer (7)
radon, asbestos, silica, arsenic, chromium, mustard gas, uranium
list the toxins that cause fibrosis (3)
silica, asbestos, cobalt
list the toxins that cause infertility
male: lead, phthiate plasticizers, cadmium
female: lead, mercury
what are the organic solvents that pose occupational health risks?
chloroform and carbon tetrachloride, pain removers, dry cleaning agents
acute exposure to high levels organic solvents
dizziness, confusion -> CNS depression and coma
exposure to lower levels organic solvents
toxic for liver and kidneys
occupational exposure to benzene and 1,3-butadiene
increased risk of leukemia, dose dependent marrow aplasia and increased risk acute myeloid leukemia (AML)
polycyclic hydrocarbons: source and effect
combustion of fossil fuels -> scrotal cancers in chimney sweeps
note: among most potent carcinogens, industrial exposure implicated in lung and bladder cancer
organochlorines: source and effect
used as pesticides (DDT), polychlorinated biphenyls (PCBs) and dioxin (TCDD)
they disrupt hormonal balance of antiestrogenic or antiandrogenic activity
dioxins and PCBs
folliculitis and a dermatosis = chloracne, characterized by acne, cyst formation, hyperpigmentation and hyper keratosis on the face and behind ears
coal dust, silica, asbestos, beryllium: pneumonconioses
asbestos -> mesothelioma, black lung
ferruginous bodies: asbestos fibers coated in iron
angiosarcomas in liver
lines food bottles and cans -> potential endocrine disruptor
why is nicotine highly addictive?
it binds to nicotinic ACh receptors in brain, stimulates release of catecholamines from sympathetic neurons -> increase in HR/BP/CO
what are the adverse effects of smoking? (8)
esophageal cancer, lung cancer, chronic bronchitis/emphysema, MI, peptic ulcer, pancreatic cancer, systemic atherosclerosis, bladder cancer***
what are the carcinogens in cigarettes?
tar, polycyclic aromatic hydrocarbons, benzopyrene, nitrosamine
what does cigarette smoke cause on the cellular level?
inflammation and increase musuc production (bronchitis) -> recruitment of leukocytes to the lung, with increase in local elastase production -> emphysema
ten-fold higher incidence of lung carcinomas for who?
asbestos workers and uranium miners who smoke