Environmental and Nutritional Disorders Flashcards
Worldwide, dramatic increase in mortality due to ? and assoc infections
HIV/AIDS
single leading global cause of health loss (morbidity & premature death)
Undernutrition
leading cause of death in developed countries
Ischemic heart disease and cerebral vascular disease
In developing countries, 5 of 10 leading causes of death (COD) are ?
Infectious disease
In the postnatal period, ~50% of all deaths in kids <5yo attributed to 3 conditions which are all preventable
Pneumonia, diarrheal disease, malaria
estimates the burden imposed by environmental dz, including those caused by communicable & nutritional dzs
Global disease burden
sum of years of life LOST due to premature mortality & disability in a population
Disability adjusted life year (DALY)
Trends of the changing burden of disease from 1990-2010:
- Cardiovascular disease = ?
- Neonatal conditions and diarrhea diseases = ?
- HIV/AIDS = ?
- Cancer = ?
- Cardiovascular disease = Going up
- Neonatal conditions and diarrhea diseases = Gone down
- HIV/AIDS = Going up a little
- Cancer = Going down
Newly evolved strains or organisms
Multidrug resistant TB
Pathogens endemic to other species that recently “jumped” to human population
HIV
Pathogens that have been present in human population, but show recent increase in incidence
Dengue fever: due to warming, spread into Southern US
Diseases worsened by heatwaves & air pollution
- Cardiovascular
- Cerebrovascular
- Respiratory diseases
Diseases from contamination
from floods & disruption of clean water supplies
- Gastroenteritis
- Cholera
- Other foodborne and waterborne infectious diseases
Vector-borne infectious dzs
- Increase temp, crop failures, and more extreme weather variations
- Malaria
- Dengue fever
Disrupted crop production
Malnutrition
Distribution, effects, and mechanisms of action of toxic agents
- Physical agents: radiation, heat
Toxicology
Definition of a poison is strictly dependent on ?
Dosage
- All substances are poisons; the right dosage differentiates a poison from a remedy
Exogenous chemicals in the environment (air, water, food, soil) that may be absorbed into the body (inhalation, ingestions, skin contact)
Xenobiotics
Most solvents & drugs are ?, facilitating their transport & penetration through the basement membrane
lipophilic
Most solvents, drugs & xenobiotics metabolized to a ? or activated to form ?
- inactive water-soluble product (detoxification)
- toxic metabolites
? pounds of toxic chemicals, incl 72 million lbs of unrecognized carcinogens, released per year in the US
4 BILLION
enzyme system (aka CYP) located primarily in endoplasmic reticulum of the liver is also present in skin, lungs, GI mucosa, & other organs
Cytochrome P-450
Function of Cytochrome P-450:
• Catalyzes reactions (rxn) that either ?, or less commonly convert xenobiotics into ? that cause cellular injury
- Both types of rxn may prod ?as a byproduct which
can cause cellular damage - Carbon tetrachloride → ? in the liver
- Metabolism of ?
- Detoxify xenobiotics
- active compounds (cmpd)
- Both types of rxn may prod REACTIVE OXYGEN SPECIES (ROS) as a byproduct which
can cause cellular damage - Carbon tetrachloride → trichloromethyl free radical in the liver
- Metabolism of acetaminophen, barbiturates, warfarin, anticonvulsants, & EtOH
Fasting and starvation can ? CYP (cytochrome P-450) activity
Decrease
Air pollution is especially hazardous to people with ?
Preexisting pulmonary or cardiac dz
Outdoor air pollution, EPA limits on ?
sulfur dioxide, carbon monoxide, ozone, nitrogen dioxide, lead & particulate matter
Countries with a lot of smog (smoke plus fog)
Beijing, Los Angeles, Houston, Cairo, New Delhi, Mexico City
& Sãu Paulo
What populations are at risk for ozone pollutants?
- Healthy adults and children
- Athletes, outdoor workers, and asthmatics
What are the effects of ozone pollutant for healthy adults and children?
- Decreased lung function
- Increased airway reactivity
- Lung inflammation
What are the effects of ozone pollutant for Athletes and outdoor workers?
Decreased exercise capacity
What are the effects of ozone pollutant for Asthmatics?
Increased hospitalizations
What populations are at risk for sulfur dioxide pollutant?
- Healthy adults
- Individuals with chronic lung disease
- Asthmatics
What are the effects of sulfur dioxide on healthy adults?
Increased respiratory symptoms
What are the effects of sulfur dioxide on individuals with chronic lung disease?
Increased mortality
What are the effects of sulfur dioxide on Asthmatics
- Increased hospitalization
- Decreased lung function
What are some outdoor air pollutants?
- Ozone
- Sulfur dioxide
- Particulate matter (soot)
- Carbon monoxide
Ozone:
• Ground level Ozone toxicity is largely mediated free radicals, which injure ?, releasing inflammatory mediators → mild sx (decreased lung function & chest discomfort)
- Exposure more dangerous for people with ? or ?
• respiratory tract epithelial cells and type I alveolar cells
- Asthma or emphysema
Sulfur Dioxide:
• Combines with ? and ?
- Produced by ? burning fossil fuels, copper smelting, and byproduct of paper mills
- Sulfuric acid and sulfuric trioxide burning sensation nose & throat, ?, and ? in those susceptible
• Ozone and particulate matter
- power plants
- difficulty breathing
- asthma attacks
Particulate matter (soot): • ? and ?
- fine or ultrafine particles less than ? µm in diameter are the most harmful; readily
inhaled into the alveoli, releasing a number of inflammatory mediators - greater than ? µm in diameter removed in the nose, or trapped by the mucociliary
epithelium of the airways
• Pulmonary inflammation & secondary cardiovascular
effects
- 10
- 10
Carbon Monoxide
• nonirritating, colorless, tasteless, odorless gas produced when there is incomplete oxidation of ?
- ? : working in tunnels, underground garages, and in highway toll booths with high exposures to automobile fumes
- ? : In a small, closed garage, the average running car can produce sufficient CO
to induce coma or death within ? minutes, and CO concentrations can also rapidly rise to toxic levels with improper use of gasoline-powered generators (e.g., during power outages)
or following mine fires
• hydrocarbons
- Chronic poisoning
- Acute toxicity
- 5
• CO kills by inducing CNS depression; widespread ? changes
- What are areas of brain affected?
- If death occurs rapidly, NO morphologic changes; longer survival the brain may be slightly ?, with ? hemorrhages and ? neuronal changes
- If pt recovers, they still can have ?, ?, and ?
• ischemic
- Basal ganglia & lenticular nuclei
- edematous
- punctate
- hypoxia-induced
- impaired memory, vision, hearing and speech
Hemoglobin has ?-fold greater affinity for CO than for oxygen
200
Systemic hypoxia: Hb = ? to ? saturated with CO
20% to 30%
Unconsciousness and death ~60% to 70% saturation,
5
Hallmark of CO
generalized cherry-red color of the skin and mucous membranes
Pollutants associated with indoor air pollution
- Wood smoke
- Bioaerosols
- Radon
- Formaldehyde
- Sick building syndrome
Indoor Air Pollution:
polycyclic hydrocarbons are carcinogens
Wood smoke
Indoor Air Pollution:
Legionnaires Dz, viral pneumonia, pet dander, fungi, molds
Bioaerosols
Indoor Air Pollution:
radioactive gas derived from uranium; Increased lung
cancer risk
Radon
Indoor Air Pollution:
Building materials, poorly ventilated trailers following disasters; carcinogen
Formaldehyde
Indoor Air Pollution:
Indoor pollutants, poor
ventilation
Sick building syndrome
Readily absorbed metal that binds to sulfhydryl groups in proteins and interferes with calcium metabolism, effects that lead to ?, ?, ?, ?, and ? toxicities
Lead
- hematologic, skeletal, neurologic, gastrointestinal, and renal toxicities
Lead:
- ? contamination for kids
- Occupational exposure: ?
- Most of the absorbed lead (80% - 85%) incorporated into ?, competes with calcium; t1/2 in bone = 20-30 years
- Flaking lead paint and soil
- battery manufacturing, pigments, car radiators, & tin cans
- bone and developing teeth *
Lead:
• Low level Pb: subtle deficits in intellect, behavioral problems, hyperactivity, poor organizational skills in ?; ? damage!!
- sensory, motor, intellectual, & psychologic impairments, including decreased IQ, learning disabilities, retarded
psychomotor development, blindness; in more severe cases, ? - Pb toxicity in mother may impair ? development in prenatal infant
• kids ; brain
- psychoses, seizures, & coma
- brain
Lead:
• CNS disturbances: ? peripheral neuropathies
- ? muscles of the wrist and fingers often first (wrist-drop), followed by paralysis of the ? muscles (foot-drop)
• adults
- extensor
- peroneal
Lead:
Radiodense deposits in metaphyses (interferes with remodeling of cartilage); also in the gums
Lead lines
Lead:
- Pb –> heme def –> ?, ?, and ? (iron-laden mitochondria)
hypochromic microcytic anemia, basophilic stippling, and ring sideroblasts
Lead:
extremely severe , poorly localized abdominal pain
Lead “colic”
Lead:
- Renal: proximal tubule damage; chronic damage = ?
interstitial fibrosis & possible renal failure
Lead poisoning effects in bones of children?
Radiodense deposits in epiphyses
Nonoccupational ways to get lead poisoning?
- Water supply
- Paint dust and flakes
- Automotive exhaust
- Urban soil
Anemia: Microcytic, hypochromic
- MCV < ? fL
- MCH < ? pg
- What is in this category?
- 80
- 27
- Lead poisoning
Metals:
Binds to sulfhydryl groups, damage CNS (developing brain) & kidney
Mercury
Mercury:
- Main sources:
- ? disease: cerebral palsy, deafness, blindness, mental retardation, & major CNS defects in children exposed in utero
- contaminated fish (methyl mercury), mercury vapors from metallic mercury in
dental amalgams - Minamata
Metal:
Interfere with cellular metabolism, –> toxicities most prominent in the GI
tract, nervous system, skin & heart (Borgia & Medici poisonings)
Arsenic
Arsenic:
- In soil & water naturally; wood preservatives, herbicides, herbal medicines, …
- Large quantities ingested –> ?, ? and ? toxicities
- 2-8 wks post exposure: ? neuropathy; ?, ?, ?
- Chronic skin changes: ? and ?
• Increased risk for cancers of lungs, bladder, and skin (multiple on ? and ?)
- GI, cardiovascular and CNS toxicities
- sensorimotor neuropathy; parathesias, numbness, pain
- hyperpigmentation and hyperkeratosis
- palms and soles
Metal:
preferentially toxic to kidneys and lungs, via uncertain mechanisms that may involve increase ROS; source: nickel-cadmium batteries, soil, plants = ?
Cadmium
- food
Cadmium
- Obstructive lung dz, ? damage, skeletal abn assoc with ?
- ?(ouch-ouch): Japan; osteoporosis & osteomalacia with renal dz
- Increased risk of ? cancer (living near zinc smelters)
- renal tubular
- calcium loss
- “Itai-Itai”
- lung
7 Occupational Health Risks
- Organic solvents (chloroform and carbon tetrachloride)
- Polycyclic Hydrocarbons
- Organochlorides
- Dioxins and PCBs
- Mineral Dusts
- Vinyl Chloride
- Bisphenol A (BPA)
Organic Solvents: (chloroform and carbon tetrachloride in degreasing and dry cleaning agents and paint removers)
- Acute exposure to high levels of vapors leads to ? –> ?. Lower levels are toxic for ? and ?
- Occupational exposure of rubber workers to ? and ? –> risk of ?
- Dose-dependent ? and increased risk of ?
- Dizziness and confusion –> CNS depression and coma
- Lower levels are toxic for liver and kidneys
- BENZENE AND 1,3-BUTADIENE
- leukemia
- Dose-dependent MARROW APLASIA and increased risk of ACUTE MYELOID LEUKEMIA (AML)
Polycyclic hydrocarbons: combustion of fossil fuels; scrotal cancers in chimney sweeps
- Among the most potent carcinogens
- Which diseases associated ?
Lung and bladder cancer
Organochlorines: synthetic lipophilic products that resist degradation; Important
organochlorines used as pesticides include ?. Nonpesticide organochlorines include polychlorinated biphenyls (?) and ?
- Disrupt ? because of antiestrogenic or antiandrogenic activity
- DDT
- PCBs and dioxin
- Hormonal balance
Dioxins and PCBs: folliculitis and a dermatosis = ? characterized by acne, cyst formation, hyperpigmentation & hyperkeratosis, face & behind ears
- Abnormalities in the ? and ?
- Chloracne
- Liver and CNS
Mineral dusts: coal dust, silica, asbestos, beryllium –> ?
- Asbestosis (workers and family members) –> ?
- ? : asbestos fibers coated in iron
- Pneumonconioses
- Mesothelioma; black lung
- Ferruginous bodies
Vinyl Chloride
- Leads to what disease ?
Angiosarcomas in liver
BPA: line almost all food bottles and cans
- potential ? disruptor (infants who drink from BPA-containing containers may be particularly susceptible to its effects)
- endocrine
90% of lung cancers are due to ?
Tobacco
Tobacco decreases overall survival through dose-dependent effects expressed as ? = average number of cigarette packs smoked/day X # years of smoking
pack-years
- Cessation of smoking greatly decreases, within 5 years, overall mortality and risk of death from ? diseases.
- Lung cancer mortality decreases 21% within 5 years, but the excess risk persists for ? years.
- cardiovascular
- 30
An alkaloid present in tobacco leaves, is not a direct cause of tobacco-related diseases, but is strongly addictive
Nicotine
Adverse effects of smoking?
- Cancer of oral cavity
- Cancer of larynx
- Cancer of esophagus
- Cancer of lung
- Chronic bronchitis, emphysema
- Myocardial infarction
- Peptic ulcer
- Cancer of pancreas
- Systemic atherosclerosis
- Cancer of bladder
Effects of Tobacco Smoke Constituents:
- Tar = ?
- Polycyclic aromatic hydrocarbons = ?
- Nicotine = ?
- Phenol = ?
- Benzoapyrene = ?
- Carbon monoxide = ?
- Formaldehyde = ?
- Nitrogen oxides = ?
- Nitrosamine = ?
- Tar = Carcinogenesis
- Polycyclic aromatic hydrocarbons = Carcinogenesis
- Nicotine = Ganglionic stimulation and depression; tumor promotion
- Phenol = Tumor promotion; mucosal irritation
- Benzoapyrene = Carcinogenesis
- Carbon monoxide = Impaired oxygen transport and utilization
- Formaldehyde = Toxicity to cilia; mucosal irritation
- Nitrogen oxides = Toxicity to cilia; mucosal irritation
- Nitrosamine = Carcinogenesis
Tobacco:
• Agents in smoke have a direct irritant effect on the tracheobronchial
mucosa, –> ? and increased ? production (bronchitis)
- Inflammation
- Mucus
Tobacco:
• Cigarette smoke causes the recruitment of leukocytes to the lung, with increased local elastase production & subsequent injury to lung tissue, leading to ?
emphysema
Tobacco:
• polycyclic hydrocarbons and nitrosamines, potent carcinogens directly involved in the development of ? cancer
- ten-fold higher incidence of lung carcinomas in ? workers and ? miners
- Multiplicative interaction: tobacco & alcohol –> ? and ?cancers
• lung cancer
- asbestos
- uranium
- laryngeal and oral cancer
Tobacco
- ? facilitate the excretion
carcinogens; however, some intermediates are electrophilic and form DNA adducts that can cause mutations in oncogenes & tumor suppressors
CYPs
• Cigarette smoking is associated with cancers of the ?
• Most common diseases caused by cigarette smoking involve the lung and
include ?
• esophagus, pancreas,
bladder, kidney, cervix & bone marrow
• emphysema, chronic bronchitis, and chronic obstructive pulmonary
disease (COPD)
• Cigarette smoking is also strongly linked to the development of ? and its major complication, ?
- Multiplicative effect on MIs when combine smoking with ? and ?
- 30,000 - 60,000 cardiac deaths in the US yearly assoc with ? smoke exposure
- atherosclerosis
- myocardial infarction
- HTN and hypercholesterolemia
- passive