PATH2220 Study Guide - Final Guide: Thorotrast, Lipoprotein, Hyperthermia
Environment and Disease
The Environment as a Cause for Disease:
• Environmental causes of disease
o Chemical
▪ Ambient exposures
▪ Occupational therapy
o Drugs
▪ Tobacco, ETOH, therapeutic drugs
o Physical agents
▪ Trauma, thermal injuries, temperature
▪ Radiation
o Nutritional deficiencies
• Bradford-Hill Consideration
o Strength of association
o Consistency of observation → reproducibility
o Specificity of key event to the disease
o Temporality → cause before disease
o Gradient → dose-response
o Plausability → biology
o Coherence → with natural history of disease
o Experimentation
o Analogy → similar known causes
• Asbestos
o Pathogenesis
▪ Reactive oxygen species catalyzed by surface iron
▪ Direct interaction → surface charge absorb proteins, DNA,
RNA
▪ Chronic inflammation
o Silicate fibrous mineral producing ferrunginous bodies
o Asbestos related disorder
▪ Pleural plaque → benign
▪ Asbestosis (fibrosis) → long term/high intensity exposure
▪ Mesothelioma → high rates in Australia
▪ Adenocarcinoma → large risk increase with addition of
smoking
• Lead
o Historical sources → paint and fuel
o Absorbed by ingestion or inhalation
o Incorporates into bone/teeth → majority of lead burden
o Children incorporate more than adults → higher intestinal
absorption and lower CNS blood-brain barrier
o Pathogenesis
▪ Disruption of heme synthesis due to affinity for sulfydril
group
▪ Competition with Ca2+ mediated messaging
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▪ Cell membrane transport interference
▪ Generation of hydrogen peroxide in endothelium
o Acute toxicity → neurotoxic
▪ GIT pain → colic
▪ Demyelination neuropathy → weakness
o Chronic toxicity
▪ Renal dysfunction
▪ Anaemia
▪ Hypertension
▪ Cognitive decline → adult
▪ Decreased IQ → children
• Other occupational chemical agents
o Cobalt, beryllium, cadmium, mercury
o Radon, uranium
o Solvents, plastics
o Herbicides
o Silica, wood dust, coal dust
• Air pollution
o Dust → large particles
o Soot/smoke → solid particles
o Fumes → suspended solids released from chemical processes
o Irritation/inflammation → asthma/COPD
o Gaseous substances
▪ Ozone
▪ Sulfur dioxide
▪ Nitrogen dioxide
▪ Production of free radicals
▪ Airway reactivity
▪ Lung inflammation → correlation vs. cause unclear
o Carbon monoxide
▪ Colourless, odorless, non-irritating
▪ From incomplete combustion of carbon sources
▪ Mechanism
• Forms carboxyhaemaglobin → no oxygen carried
• Alters conformation, dissociation curve moves to left
• Affects soft tissues
• Ultraviolet radiation
o 10% of sunlight energy
o 97% absorbed by ozone layer
o Non-ionizing
o Oxygen radicals cause direct DNA damage
o Sunburn → cell death due to induction of apoptosis
o Long-term collagen damage
• Thermal agents
o Hyperthermia
▪ Core over 41/42 degrees
▪ Causes CNS, cardiac and hepatic dysfunction →
denaturation of proteins
find more resources at oneclass.com
find more resources at oneclass.com
