environmental pathology

Question 1

the definition of “a poison” is a _____ concept dependent on ______

Answer 1

quantitative concept

dependent on dosage

Question 2

most solvents and drugs are lipophilic, why?

Answer 2

to promote transport in and around body

Question 3

phase 1 vs phase 2 drug metabolism

Answer 3

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

Question 4

nicotine and its mechanism

Answer 4

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

Question 5

physical signs of tobacco use

Answer 5

teeth and finger staining
anthracosis of lungs
smokers cough
increased phlegm

Question 6

disease caused by smoking

Answer 6

peptic ulcer
CV disease
antherosclerosis
COPD (emphysema and chronic bronchitis)
lung cancer

Question 7

lead poisoning

sources and mechanism

Answer 7

sources: paint, batteries, ceramics

absorbed and binds to sulfhydryl groups in proteins to interfere with Ca metabolism

Question 8

signs and symptoms of lead poisoning

Answer 8

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

Question 9

basophilic stippling, radiopaque lines, blue gingival line, anemia and CNS issues/neuropathy

Answer 9

lead poisoning

Question 10

mercury poisoning
source
mech
and effect

Answer 10

source is fish
mechanims: binds to sulfhydryl groups in proteins
damages CNS and kidneys

Question 11

fetal exposure to mercury causes what?

Answer 11

minamata disease
=cerebral palsy(weak/weird motions), deafness, and blindness

*developing brain is very sensitive to methyl mercury

Question 12

minamata disease

Answer 12

fetal exposure to mercury that causes cerebral palsy, deafness and blindness

Question 13

polycyclic hydrocarbons

source and effect

Answer 13

combustion of C containing fuels

potent carcinogen

Question 14

vinyl chloride

source and effect

Answer 14

PVC and polyvinyl resins

hepatotoxicity, liver angiosarcoma

Question 15

benzene

source and effect

Answer 15

rubber

causes leukemia

Question 16

organochlorines

source and effect

Answer 16

pesticides (DDT)

endocrine dysfunction (antiestrogen and antiandrogen)

Question 17

organophosphate pesticides

mechanism and effect

Answer 17

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

Question 18

dioxin, PCB

Answer 18

food contamination (rice oil)

causes chloracne and folliculitis

Question 19

arsenic poisoning

sources, mech, and effects

Answer 19

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)

Question 20

what is there an increased risk of with arsenic poisoning

Answer 20

cancer (squamous cell carcinoma)

bowens disease = early SCC in situ (red scaly skin)

Question 21

mees lines and hyperkeratosis?

Answer 21

arsenic poisoning

Question 22

cadmium poisoning

Answer 22

mining, electroplating, paint, and batteries

toxic to lungs and kidneys due to ROS
obstructive lung dz and renal tubular damage

Question 23

sources of carbon monoxide poisoning?

Answer 23

autofumes, cigarettes, natural gas, unvented heaters = CO is made by incomplete combustion

classic case = dead guy with dead pet with unvented space heater

Question 24

mechanism of CO poisoning

Answer 24

o 200x greater affinity for Hgb than O2;

Binds to Hgb, decreasing available sites for oxygen –> less oxygen and CO2 carried

Question 25

effect and signs of CO poisoning

Answer 25

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

Question 26

what two toxins cause livor mortis?

Answer 26

cherry red coloration cyanide and CO

Question 27

acetaminophen overdose

Answer 27

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

Question 28

treatment for acetominophen overdose?

Answer 28

n-acetylcysteine

Question 29

aspirin overdose

Answer 29

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

Question 30

cocaine

Answer 30

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

Question 31

heroin

Answer 31

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

Question 32

thermal injuries - 1st degree - 2nd degree - 3rd degree - 4th degree can cause?

Answer 32

* 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

Question 33

hyperthermia cause of heat cramps? of heat exhaustion? of heat stroke? 2 serious conditions?

Answer 33

• 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

Question 34

hypothermia

Answer 34

* 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

Question 35

electrical injury causes

Answer 35

burns and ventricular fibrillation

Question 36

ionizing radiation | effects

Answer 36

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

Question 37

what doesnt count for cause of death?

Answer 37

``` o cardiac arrest o respiratory arrest o Cardiorespiratory arrest o Renal failure o Asystole ```

Question 38

cause of death

Answer 38

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

Question 39

mechanism of death

Answer 39

the nonspecific final common pathway by which the cause of death exerts its lethal effect • Cardiorespiratory arrest, exsanguination, hypoxia, etc

Question 40

COD vs mechanism of death

Answer 40

* Cause of death = etiologically specific; can stand alone on death certificate * Mechanism of death = broad differential; cannot stand alone on a certificate

Question 41

manner of death

Answer 41

– 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!

Question 42

smoke inhalation can cause..

Answer 42

.pulmonary edema

Question 43

metabolizing a toxin MOST often is the enzyme

Answer 43

cytp450

Question 44

ceramics, basophilic stippling, radiopaque lines -->

Answer 44

lead poisoning

Question 45

necrosis of pallidus globus

Answer 45

kerosene heated, dead dog, dead man -->you see | CO poisoning

Question 46

cherry red livor mortis....what kind of poisoning?

Answer 46

CO poisoning | red color from pooling of blood

Question 47

WHAT Poisoning inhibits heme synthesis?

Answer 47

lead poisoning causes microcytic hypochromic anemia

Question 48

treatment for lead poisoing?

Answer 48

chelating agent

Question 49

dont eat what in preganncy?

Answer 49

fish - mercury can affect fetuses!!!

Question 50

what substances are inhibitors of acetylcholinesteras?

Answer 50

organophsophates (insecticides)

Question 51

antidote for organophosphate poisoning?

Answer 51

atropine for symptoms ( and treat w pralidoxime

Question 52

neuromuscular weakness (flacidity) with salivation...what kind of poisoning

Answer 52

caused by organophosphate poisoning (pesticides like malathion/parathion)

Question 53

what poisoning interferes with mitochondrial ATP formation/cell metabolism?

Answer 53

arsenic

Question 54

hepatic lesions associated with arsenic

Answer 54

liver angiosarcoma hepatic necrosis cirrhotic portal htn hepatitis

Question 55

ingested arsenic causes...

Answer 55

mees lines on nails

Question 56

neutrophil elastases breakdown lung tissue effect on nicotine on this process?

Answer 56

inactivates the inhibitors of the elastases --> enhanced tissue destruction in lungs

Question 57

mutations in progression to squamous cell carcinoma?

Answer 57

p16, p53, then cyclin D