Lecture 24: Environmental Pathology Flashcards
Toxicology
Study of poisons; distribution, effects, mechanism of action
2 main paths of xenobiotic metabolism
- ROS byproduct generation by cytochrome p-450 enzymes (CYP)
- Conversion of nontoxic to reactive forms leading to cell repair and toxic effects
Smog
Smoke + fog; gaseous components from fossil fuel combustion
- O3 (ozone): reactive oxidant
- CO: competitive Hb binding
- Fine/ultrafine particulars: inflam. via alveolar macrophages
Indoor air pollutants
- Formaldehyde: asthma, irritation
- Radon gas: uranium derived, radioactive
- Asbestos fibers: mesothelioma*, lung cancer
Heavy metal toxins
- Lead: hematologic, skeletal, neurologic effects; binds sulfhydryl groups
- Mercury: tremors, confusion, retardation; binds sulfhydryl groups
- Arsenic: acute GI, CV, CNS dmg; replaces ATP Pi groups
- Cadmium: increases ROS production
Burtonium lead lines
Lead lines in bones, gums due to lead sulfide
Organic chemical toxins
Heavily used in manufacturing; issues mainly in disposal
1. Volatile compounds e.g. chloroform, benzene
2. Manufactured compounds:
- PCBs, dioxins, DDTs (chloracne, cancer, liver dmg)
- VCMs (PVC products; liver angiosarcoma)
- Phthalate esters (plastics; reproductive toxin)
- BPAs (bottles/cans; estrogen mimic agonist -> proliferative effects)
- PFAs (also a forever chemical; widely used/persistent)
Micro/nanoplastics
Ingested and inhaled, ubiquitous, long lasting. Effects still being understood
Tobacco use
- Toxic FX from cigarettes -> emphysema (elastin loss) -> COPD
- Mediated by neutrophils + macrophages producing excess proteases, ROS, inflam., MMPs
- Alpha-1-anti-trypsin deficit can be congenital or acquired
- Leukoplakia from smokeless tobacco; preneoplastic lesion
Oral cavity/tongue cancer
Mainly SCC
Risks: leukoplakia, tobacco/alc., HPV
- Lower lip, mouth floor, lateral tongue
EVALI
E-cigarette/vaping associated lung injury; acute lung injury driven by diffuse alveolar dmg w/ ATII pneumocyte hyperplasia
- Mediated by additives being heated and inhaled
Alcohol
- Toxicity acetaldehyde gen. via alc. DH; decreases NAD too
- NAD depletion -> hepatic FA accumul.
- Tolerance depends on enzyme variants (fast ADH, slow ALDH -> less tolerance)
Alcoholism
Acute: CNS depression, impairment
Chronic: liver, GI, CV injury e.g. fatty liver -> fibrosis -> cirrhosis
Mechanical injury
- Abrasions, contusions
- Lacerations: intact bridging tissue, blunt object
- Incisions: severed bridging tissue, sharp object
- Penetrating/perforating trauma
Thermal injuries
- Burns
- Hyper/hypothermia
Burns
Severity depends on depth, %BSA, internal dmg
- Superficial, partial, full thickness depending on epidermal/dermal involvement
Hyperthermia
Heat cramps -> exhaustion -> stroke
- High core temp. -> vasodilation -> reduced blood flow to brain/heart
Hypothermia
Major risk assoc. w/ homelessness
Systemic: core temp drop
Local: frostbite, trench foot, ischemia, crystallization
Electrical injuries
- Burns, V-fib, cardiac/respir. center failure
- Severity depends on current type/intensity, path, tissue resistance, duration
e.g. Ferning burns from lightning strike (Lichtenberg figure)
Radiation injury
2 mechanisms:
1. Direct DNA dmg
2. Indirect DNA dmg by free radical formation
- Highest sensitivity in most proliferative cells (HSCs, GI epithelium, germ cells)
- Vasc. dmg, inflam., fibrosis (lung radiopneumonitis)
UV radiation
- Acute injury
- Long term elastin/collagen degen., cataracts, melanoma
