environmental pathology Flashcards
the definition of “a poison” is a _____ concept dependent on ______
quantitative concept
dependent on dosage
most solvents and drugs are lipophilic, why?
to promote transport in and around body
phase 1 vs phase 2 drug metabolism
phase 1 = hydrolysis, reduction or oxidation using cytp450 = rns that convert parent drug to water soluble active metabolites by adding or unmasking a polar group
phase 2 = glucuronidation, sulfation, methylation, and conjugation w glutathione –> conjugation rxns that increase water solubility with a polar group to INACTIVATE it for renal excretion
nicotine and its mechanism
alkaloid
not direct cause of tobacco-related dz, but very addictive
a stimulant, agonist at nicotinic choliergic receptors
Quickly reaches brain via blood and activates nicotinic Ach receptors inducing release of many chemical messengers
= serotonin, Ach, norepi, epi, vasopressin, dopamine, B-endorphin
–> increased BP, vasoconstriction, and tachycardia
physical signs of tobacco use
teeth and finger staining
anthracosis of lungs
smokers cough
increased phlegm
disease caused by smoking
peptic ulcer CV disease antherosclerosis COPD (emphysema and chronic bronchitis) lung cancer
lead poisoning
sources and mechanism
sources: paint, batteries, ceramics
absorbed and binds to sulfhydryl groups in proteins to interfere with Ca metabolism
signs and symptoms of lead poisoning
o Most deposits into bone and interferes with cartilage remodeling –> radiopaque xray lines at epiphyses
o Leads to: demyelination and CNS defects –> developmental issues in kids, encephalopathy (edematos brain with compressed ventricles and flat gyri), peripheral neuropathy
- blue lines at gingival margins
- GI issues
*Anemia
Causes anemia by interfering with heme synthesis –> accumulation of protoporphyrins and basophilic stippling
Treat anemia with chelation
o Kidneys show proximal tubular damage with intranuclear inclusions
basophilic stippling, radiopaque lines, blue gingival line, anemia and CNS issues/neuropathy
lead poisoning
mercury poisoning
source
mech
and effect
source is fish
mechanims: binds to sulfhydryl groups in proteins
damages CNS and kidneys
fetal exposure to mercury causes what?
minamata disease
=cerebral palsy(weak/weird motions), deafness, and blindness
*developing brain is very sensitive to methyl mercury
minamata disease
fetal exposure to mercury that causes cerebral palsy, deafness and blindness
polycyclic hydrocarbons
source and effect
combustion of C containing fuels
potent carcinogen
vinyl chloride
source and effect
PVC and polyvinyl resins
hepatotoxicity, liver angiosarcoma
benzene
source and effect
rubber
causes leukemia
organochlorines
source and effect
pesticides (DDT)
endocrine dysfunction (antiestrogen and antiandrogen)
organophosphate pesticides
mechanism and effect
irreversible inhibitors of acetylcholinesterase by phosphorylating active site
–> results in abnormal nerve transmission, NTs aren’t broken down (neurotoxicity)
o Signs due to excessive cholinergic stimulation: pupil constriction, blurred vision, muscular paralysis, diarrhea, abdominal cramps, salivation, bronchoconstriction
In kids: lethargy, weakness, salivation, and seizures common (not common in adults)
o Histology –> demyelinated nerves, atrophic muscle fibers, and pale foci of demyelination/necrosis
dioxin, PCB
food contamination (rice oil)
causes chloracne and folliculitis
arsenic poisoning
sources, mech, and effects
wood preservatives, smelting industry and mines, groundwater in china
interferes with cellular oxidative phosphorylation
effects on SKIN, Gi, nervous system and heart
- -skin lesions + n/v/d
- -sensorimotor neuropathy in 2-8 weeks (demyelination)
- -chronic –> hair, nails and skin
- ——-mees lines in nails (white striae)
- ——-skin hyperpigmentation and hyperkeratosis (thick and scaly)
- ——bowens disease (early SCC Insitu; red scaly skin)
what is there an increased risk of with arsenic poisoning
cancer (squamous cell carcinoma)
bowens disease = early SCC in situ (red scaly skin)
mees lines and hyperkeratosis?
arsenic poisoning
cadmium poisoning
mining, electroplating, paint, and batteries
toxic to lungs and kidneys due to ROS
obstructive lung dz and renal tubular damage
sources of carbon monoxide poisoning?
autofumes, cigarettes, natural gas, unvented heaters = CO is made by incomplete combustion
classic case = dead guy with dead pet with unvented space heater
mechanism of CO poisoning
o 200x greater affinity for Hgb than O2;
Binds to Hgb, decreasing available sites for oxygen –> less oxygen and CO2 carried
effect and signs of CO poisoning
o Hypoxia leads to ischemic change in the CNS and basal ganglia
—-necrosis of globus pallidus
o cherry red color = livor mortis
headaches, dizzy, nausea, confusion
what two toxins cause livor mortis?
cherry red coloration
cyanide and CO
acetaminophen overdose
o 95% is Detoxed in liver by phase 2 enzymes and excreted as glucoronate
BAD PATH: 5% is processed by cyp2E1 which converts it to NAPQ –> protein adducts and lipid peroxidation –> liver injury
o High doses Can cause hepatocellular injury, centrilobular necrosis, and acute liver failure
o Treatment for overdose: N-acetylcysteine
treatment for acetominophen overdose?
n-acetylcysteine
aspirin overdose
Overdose causes alkalosis (stimulates resp. Centers) followed by metabolic acidosis
o Chronic toxicity = h/a, dizzy, tinnitus, confusion, n/v/d
o Commonly causes acute erosive gastritis and GI bleeding
cocaine
o Leaves of coca plant; snorted, injected or crystallized to crack (more potent)
o Very addictive; metabolite is benzoylecgonine (BE)
o CV effects =sympathomimetic, blocks uptake of dopamine –> tachycardia, HTN, vasoconstriction, platelet aggregation and lethal arrythmias
heroin
o Opioid from poppy plant; synthetic drug injected
o Causes euphoria, pulmonary edema, infections (skin popping)
–can cause sudden death
o Methadone used to treat addicts
thermal injuries
- 1st degree
- 2nd degree
- 3rd degree
- 4th degree
can cause?
- 1st degree = confined to epidermis
- 2nd degree = dermis/partial thickness
- Full thickness = 3rd degree to subcutaneous; 4th degree to muscle
- Internal injuries from inhalation
- Shock sepsis and respiratory effects
hyperthermia
cause of heat cramps?
of heat exhaustion?
of heat stroke?
2 serious conditions?
• Heat cramps – loss of electrolytes
• Heat exhaustion – sudden collapse, CV failure to compensate for hypovolemia
• Heat stroke – high temp, humidity, exertion
o rhabdomyolysis or inherited malignant hyperthermia
hypothermia
- body temp falls below 90 degrees
- directly causes high salt in cells due to crystallization of water
- indirectly causes circulatory changes –> vasoconstriction, increased blood viscosity, ischemic injury
electrical injury causes
burns and ventricular fibrillation
ionizing radiation
effects
energy traveling in waves or high speed particles and causes DNA damage
embryonic destruction of neurons/glial cells
adult brain is resistant
effects on skin, lungs, lymph nodes, GI, gonads, and blood/bone marrow
what doesnt count for cause of death?
o cardiac arrest o respiratory arrest o Cardiorespiratory arrest o Renal failure o Asystole
cause of death
the disease/injury that initiated the chain of events that brought about death
• initiating disease or condition; may precede death by seconds or years; Usually determined by autopsy
• may not be obvious if occurred in remote past
• many intermediate illnesses or conditions may connect the COD to fatal condition
–a proximate –> intermediate –> immediate
mechanism of death
the nonspecific final common pathway by which the cause of death exerts its lethal effect
• Cardiorespiratory arrest, exsanguination, hypoxia, etc
COD vs mechanism of death
- Cause of death = etiologically specific; can stand alone on death certificate
- Mechanism of death = broad differential; cannot stand alone on a certificate
manner of death
– how the cause of death came about or the circumstances under which the person died; determined by death investigation
• Natural
• Accident – neither he/she nor someone else brought it on and it was not reasonably foreseeable
• Suicide – “self murder”; victim knowingly engaged in an act that could reasonably end life
• Homicide – victim killed by another person
*undetermined
1 yr + 1 day rule does NOT apply gunshot to head 10 yrs prior that results in a lethal seizure 10 yrs later is a HOMICIDE!
smoke inhalation can cause..
.pulmonary edema
metabolizing a toxin MOST often is the enzyme
cytp450
ceramics, basophilic stippling, radiopaque lines –>
lead poisoning
necrosis of pallidus globus
kerosene heated, dead dog, dead man –>you see
CO poisoning
cherry red livor mortis….what kind of poisoning?
CO poisoning
red color from pooling of blood
WHAT Poisoning inhibits heme synthesis?
lead poisoning causes microcytic hypochromic anemia
treatment for lead poisoing?
chelating agent
dont eat what in preganncy?
fish - mercury can affect fetuses!!!
what substances are inhibitors of acetylcholinesteras?
organophsophates (insecticides)
antidote for organophosphate poisoning?
atropine for symptoms (
and treat w pralidoxime
neuromuscular weakness (flacidity) with salivation…what kind of poisoning
caused by organophosphate poisoning (pesticides like malathion/parathion)
what poisoning interferes with mitochondrial ATP formation/cell metabolism?
arsenic
hepatic lesions associated with arsenic
liver angiosarcoma
hepatic necrosis
cirrhotic portal htn
hepatitis
ingested arsenic causes…
mees lines on nails
neutrophil elastases breakdown lung tissue
effect on nicotine on this process?
inactivates the inhibitors of the elastases –> enhanced tissue destruction in lungs
mutations in progression to squamous cell carcinoma?
p16, p53, then cyclin D
