Flashcards in Ch10: Environmental Pathology Deck (252):
What are three major determinants of our health?
1. Air we breath
2. Food and water we consume
3. Exposure to toxic agents
What is an environmental disease?
Condition caused by exposure to chemical or physical agents in a person's environment
What is overall fatality rate of occupational injuries?
4.8 per 100,000 workers
Who set the standard for reporting health information?
Global Burden of Disease
What is the GBD statistic for assessing premature mortality and disease morbidity?
DALY (Disability adjusted life year)
What is the DALY statistic?
adds the years of life lost to premature mortality with the years lived with illness and disability.
What is said to increase due to human activity in regards to climate change?
Causes of increased CO2? (2)
1. Combustion of hydrocarbons in automobiles and energy plants
Problems with human health in regard to climate change? (4)
1. CV, Cerebrovascular, Respiratory disease
2. Gastroenteritis and infectious disease
3. Vector-borne infectious diseases
What is the definition of poison?
A dose that causes harmful effects instead of helpful
How many pounds of carinogenic toxic chemicals are released per year in the US?
4 billion pounds
What 4 agencies determine exposure limits?
The EPA regulates what?
Exposure to peticides, toxic chemicals, water and air pollutants
The FDA regulates what?
drugs, medical devices, food additives, and
What does OSHA mandate?
employers provide safe working conditions for
What does CPSC regulate?
other products sold for use in homes, schools, or
What are xenobiotics?
Exogenous chemicals in the air, water, food
and soil that may be absorbed into the body
through inhalation, ingestion, and skin contact
Where do xenobiotics act? (2)
Site of entry
Transported to distant tissues by BV's
What xenobiotics are metabolized to form inactive water-soluble products or activated to form toxic metabolites? 2
Most important catalyst of phase I reactions is what?
Cytochrome p450 system
Carbon tetrachloride is metabolized to what in the liver?
Toxic trichloromethyl free radical
Benzo-alpha-prene is metabolized to what?
DNA-binding metabolite carcinogen
Xenobiotics are typically eliminated how?
Phase I reaction
Phase II reaction to soluble metabolite
Eliminated from body
What does Radon cause?
Lung disease and cancer
EPA has limits for what 6 pollutants?
2. Nitrogen oxides
3. Sulfur dioxide
Smog is what?
Smoke and fog
What leads to formation of ozone layer?
Interaction of UV radiation and oxygen in the stratosphere
Why is the ozone layer good?
Absorbs the most dangerous UV from sun
What causes ozone layer loss?
Halocarbons like CFP's
Toxicity of ozone is due to what?
Production of free radicals that injury lung epithelial cells and Type I alveolar cells
How does ozone cause release of inflammatory mediators?
Oxidizes lipids to H2O2 which acts as irritant
Overall effect of ozone on lungs? (3)
1. Increase epithelial permeability
2. Increased reactivity of airways
3. Decreased ciliary clearance
Nitrogen dioxide does what in the airway?
Dissolves in water to form nitric acid which damages airway epithelium
Sulfur dioxide is produced by who? 2
Power plants burning coal and oil
Byproduct of mills
SO2 is absorbed in airways where it releases what? (3)
Effect of this?
H+, HSO- (bisulfite), SO3 (sulfite)
Particulate matter like soot is most hazardous at what size?
Ultrafine (<10 um)
What is effect of ultrafine soot in lungs?
Phagocytosed by macrophages which causes release of inflammatory mediators that damage lungs
What is anthracosis?
Black pigment in lungs
3 main effects of soot in lungs?
1. Cytokine release systemically
2. Increased blood viscosity
3. Autonomic changes affecting the heart
Carbon monoxide has what four characteristics?
What produces CO?
Incomplete oxidation of carbon materials
Greatest danger of CO toxicity is when?
Working in confined environments with high exposure (in a garage will kill in 5 minutes)
Carbon monoxide effects? 2
1. CNS depressant
2. Binds to hemoglobin causing loss of oxygen
Severe hypoxia occurs when with CO?
Death and loss of consciousness occur when with CO?
60-70 percent saturation
Indoor air pollution includes? (4)
1. tobacco smoke
4. Wood smoke (NO's, soot, hydrocarbons)
Formaldehyde is found in what especially?
Radon is a decay product of what?
Uranium and is found in soil
Asbestos fibers are found where?
Houses built before 1970
Bioareosols are used for what?
Aerosolization of bacteria
What is the famous bioaerosol exposure?
Lead exposure occurs through what? 3
Air, food and water
Most absorbed lead goes where?
What does it compete with?
How is it seen radiographically?
Bone and teeth
Lead lines along growth plates
Is acute poisoning of lead common?
Acute Lead poisoning is seen with what main symptoms? 2
Why are children affected more than adults by lead?
1. Absorb 50% of ingested lead compared to adults' 15%
2. More permeable blood brain barrier
Which nervous system is affected more in children?
More in adults?
Children = CNS
Adults = PNS
How does lead present in terms of blood?
Microcytic anemia with coarse basophilic stippling
When will you see the microcytic anemia with coarse basophilic stippling in lead toxic patients?
At 40 ug/ml
Arsenic intereferes with what?
Cellular longevity by interfering with oxidative phosphorylation
Signs and symptoms of acute arsenic poisoning?
Long term exposure to arsenic leads to what?
Night blindness due to Vitamin A deficiency
3 cancers caused by long term arsenic exposure?
1. Cutaneous basal cells
2. Squamous cell
3. Lung carcinomas
Cadmium is generated where? 2
Cadmium nickel batteries
Toxicities of cadmium include what? 4
1. Obstructive Lung disease
2. End stage renal disease
3. Skeletal problems
4. Lung carcinomas
Three main forms of mercurcy?
2. Inorganic: Mercury chloride
3. Organic: Methyl mercury
Modern sources of mercury? (4)
1. Contaminated sea food
3. Gold mining
Clinical manifestation of mercury? 4
1. Nervous system: CNS malfunction and peripheral neuropathies
2. Kidney injury
3. Tremors/bizarre behavior
What is methyl mercury particularly toxic to?
Chronic exposure of mining and industrial chromium and nickel has what effect?
Increased nasal and lung carcinomas
Cause of heart disease? (4)
Cause of nasal cancer? 2
1. Isopropyl alcohol
2. Wood dust
Cause of lung cancer? 7
6. Mustard gas
Cause of COPD? 2
Cause of respiratory irritation? 3
2. sulfur oxide
Cause of fibrosis in respiratory?
Organic solvents are readily obsorbed where? 2
Organic solvent acute exposure can lead to what?
Huffing involves inhalation of what?
Benzene is metabolized by what?
What do its metabolites cause? (3)
1. Bone marrow toxicity
3. Aplastic anemia
Polycyclic aromatic hydrocarbons are composed of what?
Aromatic rings in a flat plane
PAH's are found in what? 4
What are PAH's considered?
Most potent chemical carcinogens
PAH's are so potent why?
Very common and highly carcinogenic
Industrial exposure to PAH's is linked to what? 2
1. Bladder carcinoma
2. Lung carcinoma
Organochlorines are lipophilic products that can resist what?
Organochlorines have what type of activity?
Anti-estrogenic and Anti-Androgenic leading to decreased fertility rates
What are most organochlorines used for?
Non-pesticide organochlorines are known to cause what? 4
2. CNS probs
3. Hepatic probs
4. Induce cytochromes
What is chloracne?
Hyperpigmentation and hyperkeratosis of face and ear
Vinyl chloride is used to produce what?
Polymer polyvinyl chloride (PVC)
What will vinylchloride cause?
Anglosarcoma of liver
Mineral dust inhalation causes what?
Chronic, non-neoplastic lung disease "Pneumoconioses"
1. Black lung
What is the most preventable cause of human death?
How many people die due to tobacco smoke in US a year?
What are the causes of death in smokers? (10)
1. Lung cancer
2. Esophageal cancer
3. Bladder cancer
4. Oral cavity/URT cancer
5. Pancreatic cancer
10. Respiratory infections
What is the number 1 cancer killer of men and women?
What % of lung cancers is tobacco responsible for?
Where does lung cancer rate in terms of cancer incidence in men and women?
What are two ways to reduce your cigarette cancer risk?
1. Delay onset of smoking habits
Is nicotine carcinogenic?
No, just a physical addiction
What does nicotine do?
Binds to receptors in brain causing release of ACh that increases HR and BP, and contractility and output
How are the inhaled agents of cigarette smoke harmful? (3)
1. Act on mucus membranes
2. Swallowed in saliva
3. Absorbed in blood stream to act on distant organs
How many components of tobacco are carcinogens?
Tobacco smoke increases risk of atherosclerosis how?
1. In addition to HT and hypercholesterolemia
2. Increases platelet adhesion and aggregation --> Vascular thromboses --> MI's and CVA's
3. Increase hypoxia --> increase arrhthmias and MI's
Effect of tobacco on respiratory? 2
1. Allows for RT infections by destroying cilia
2. Irritation of respiratory epithelium leading to COPD
Effect of tobacco on GI?
Peptic ulcer disease
Effects of tobacco on fetus?
1. Fetal hypoxia
2. Low birth weight
4. increased spontaneous abortion
5. Complications at delivery mainly with placenta
Effect of smoking on kids? (3)
Differences between tobacco chewing and smoking? 4
1. Lungs spared
2. Oral cavity irritation
3. Increased caries, gingivitis, loss of feeth
4. stains tooth enamel
What are the numbers used to compare wine, beer, and liquor alcohol contents?
5 ounces of 24 proof wine
12 ounces of 10 proof beer
1.5 ounces of 80 proof liquor
Can one die from acute alcohol intake?
How is ethanol absorbed in GI?
Oxidation of ethanol in metabolism produces what?
Toxic agents like acetaldehyde
How is ethanol oxidized to acetaldehyde? 3
1. In peroxisome by catalase
2. In cytosol by ADH
3. In microsomes by CYP2E1
How is acealdehyde converted to acetic acid?
ALDH in mitochondria
What is the genetic polymorphism in alcohol dehydrogenase?
50% of Asians have increased activity due to point mutation so that they convert more than normal ethanol to acealdehyde leading to flushing, nausea, and tachycardia
Who has higher levels of gastric alcohol dehydrogenase activity?
What does this mean?
Women develop higher blood alcohol levels than men after same amount of ethanol
Acute ethanol toxicity includes? (4)
1. CNS depressant
4. Acetaldehyde effects --> Esophageal and oral cancers
Chronic ethanol toxicity includes?
1. Liver (steatosis, hepatitis, cirrhosis, liver carcinoma)
2. Nervous system: Wernicke-Korsakoff, PN's
3. GI tract: Ulcers, esophageal varices, malnutrition
4. Pancreas: Pancreatitis
5. Cardiac: cardiomyopathy, HT
6. Cancers: Oral, esophageal, liver
7. Pregnancy/Fetus: FAS
What is most common cause of preventable congenital retardation in US?
Rate of it?
FAS (1-5 per 1000 births)
Ethylene glycol is metabolized by what?
To produce what?
Glycolic acid and oxalate
Glycolic acid is responsible for what? 92)
1. CNS probs
2. Anion gap acidosis
Oxalate does what?
Binds calcium to form calcium oxalate that deposits in kidneys.
Methanol is metabolized by what?
To form what?
Formaldehyde and Formic acid
Methanol metabolites cause what? (4)
1. Ocular toxicity (blurred vision and blindness)
4. Elevated anion gap acidosis
What do you give to patients with ethylene glycol and methanol overdose? 2
Ethanol or fomepizole to compete for ADH enzyme spots.
Elevated anion gap acidosis is do to what? 9
How many women use hormonal contraception?
What % of reproductive women use reversible methods?
greater than 100 million
What population uses oral birth control pills the most?
Teenagers and Twentys
Adverse effects of OBC's include?
2. CV disease
3. Liver tumors
OBC's thromboembolism increases DVT risk how much?
What factors increase risk? (5)
Factor V mutation
Older than 35
Combined estrogen/progestin OBC's
Increased thrombotic risk in OBC's seems due to what?
Acute phase response that increases CRP and coagulation factors (7, 9, 10, 12, 13) and a reduction in anticoagulants (protein S and anti-thrombin III)
Explain OBC and CV risk? 2
Being older than 35
Smoker of all ages
What type of liver tumors with OBC's?
Benign hepatic adenoma
HRT has what risks? 3
1. Endometrial hyperplasia/carcinoma
2. Increased breast carcinoma risk
3. Venous thrombosis and PE (Especially first 2 years of use and if you have other risk factors)
Anabolic steroids can have what effects? 7
1. Stunted growth
2. Acne, gynecomastia, and testicular atrophy in males
3. Acne, hirsutism, and menstrual changes in females
6. Hepatic cholestasis
7. Increased prostate carcinoma
What is the most commonly used analgesic in the US?
What percentage of acute liver failure disease is acetaminophen caused?
At therapeutic doses what happens in metabolism of acetaminophen?
1. 95% phase II detox in liver and excreted in urine
2. 5% cytochromes convert it to NAPQI which is a reactive metabolite that will harm the liver.
What is the therapeutic window?
The window where the therapeutic dose doesn't become toxic
Acetaminophen has a small or large therapeutic window?
Overdoses of acetaminophen cause what?
GI problems and liver problems
What type of therapy is used to reverse acetaminophen toxicity?
What location in the liver has the lowest O2 concentration?
Around central vein
Where does acetaminophen cause damage in the liver?
Around central vein
Aspirin has what three effects?
1. Irreversibly inhibits COX-1
2. Modifies activity of COX-2
3. Blocks production of thromboxane A2
Acute overdose consequences of aspirin are morphologic or metabolic?
What happens in an acute aspirin overdose?
1. Respiratory alkalosis
2. Metabolic acidosis
Acidosis in aspirin overdose allows what?
Formation of non-ionized salicylates which go to brain and cause nausea/coma
Chronic toxicity of aspirin (salicylism) involves what dose?
3+ grams daily for long periods
Symptoms of aspirin chronic toxcitiy?
1. Headaches and tinnitis
2. GI problems
4. Abnormal bleeding.
Aspirin and tylenol together is hard on what?
Crystallization of pure cocaine yields what?
What does cocaine produce?
Euphoria and stimulation
Does cocaine have physical dependence?
No, but severe psychological
Cocaine blocks reuptake of what? (3)
Cocaine also prolongs what?
And blocks what other reuptake?
Dopaminergic effects in brain pleasure areas
Epinephrine and norepinephrine
Clinical clues for possible cocaine abuse?
3. Nasal septum problem
4. needle tracts
What is heroin?
Opioid narcotic from opium or synthesized from morphine
What is used in treatment of heroine addiction?
Has what problem?
Killing people in overdose
IV heroin and other opiates cause what?
1. CNS depression: hypoventilation (respiratory acidosis), GI issues, seizures
2. Pulmonary injury: Edema, emboli, granulomas
3. Infections: Skin, heart valves, liver, and lungs
What are two main infections due to heroin?
1. Staph aureus on tricuspid valve
2. Viral hepatitis
Evidence of heroin addiction? (4)
1. Narcotic abstinence syndrome
3. Renal disease: Focal segmental glomerulosclerosis
4. Cutaneous scars, hyperpigmentation of skin over veins and thrombosed veins.
Two types of amphetamines?
Methamphetamine acts how?
Releases dopamine --> Inhibits presynaptic neurotransmission at corticostriatal synapses, slowing glutamate release --> Euphoria with a crash
How does MDMA/ecstasy work?
Euphoria and hallucinations due to altered serotonin levels in CNS
Marijuana is from what?
Cannabis sativa plant with high levels of THC
Marijuana has what effects?
1. Distorts sensory and motor
2. Euphoria, paranoia, bad judgment
3. Increased appetite and dry mouth
4. Irritant and carcinogen
Cycad flour contains what?
How do you avoid the toxins in cycad flour?
Cut seeds and soak them to get the toxin out.
Cycasin poison has what effect?
Degenerative neurologic disorder
Aflatoxins are natural toxins produced by what?
Where is aspergillus found?
In stored grains
Aflatoxin effect on humans?
1. Toxic to liver
2. Carcinogenic to liver
Unintentional injuries/trauma rank where in deaths of adolescents and adults under 44 y/old?
What percentage of unintentional injuries involve ethanol?
Motor vehicle accidents caused by what?
1. Impact of vehicle on person
2. Ejection from vehicle
3. Trapped in vehicle
4. Alcohol use
What is an abrasion?
superficial epidermis is torn off by friction or
Is there scarring in abrasion healing?
No, but risk of infection
What is a laceration?
irregular tear in the skin produced by tissue
stretching due to blunt force
Lacerations are typically seen how? 2
1. bridging strands of fibrous tissue or
blood vessels across the wound
2. immediate margins are frequently hemorrhagic
Incisions are usually made by what?
Sharp cutting object
Describe margins and bridging in incisions?
Margins = clean
What is a stab wound?
depth of wound greater than length of
What is puncture wound?
deep penetrating wounds made by a
long thing object such as a nail or ice pick
What is penetration wound?
open wound that enters and
exists the body
What is a gun shot wound?
caused by bullets or pellets fired from a gun, can be penetrating if the bullet or pellets exit the body
What is a contusion?
blunt force that damages small vessels and causes extravasation of blood into tissues
What is a superficial burn?
(1st degree): Confined to
What is a partial thickness burn?
(2nd degree): Injury to the
dermis (at least the deeper portions of the dermal
appendages are spared to regenerate epithelium)
What is a full thickness burn?
Extends to subcutaneous
tissue (3rd degree) and may involve muscle (4th
What is destroyed in full thickness?
the epidermis and dermis
and anesthesia due to nerve ending destruction
What will cause a burn to be fatal?
Any burn exceeding 50% of total BSA
What happens if burn is above 20% BSA?
Fluid shifts to interstitial compartments --> Hypovolemic shock
What causes the hypovolemic shock in a burn? 2
1. Increase in interstitial osmotic pressure
2. Neurogenic and mediator induced vascular permeability
Injury to airways and lungs in thermal injury may result from what? 2
1. Direct effect of heat
2. Inhalation of smoke
What is teh most common seconday infection in thermal injury?
What other two?
Candida and s. aureus
What causes heat cramps?
What is the hallmark
What is the mechanism?
Loss of electrolytes through sweating
Cramping of voluntary muscles during exercise is
Heat dissipating mechanisms able to maintain
normal core temp
What is the onset of heat exhaustion?
Why does it occur?
failure of the cardiovascular system to
compensate for hypovolemia, secondary to water
What is heat stroke associated with? (2)
High ambient temperature
What fails in heat stroke?
Thermoregulatory mechanisms fail, sweating
ceases, and core body temp rises – multi-organ
dysfunction - death
What is the sign of heat stroke?
Rectal temp above 106 F
What is the mechanism of heat stroke?
Mechanism is peripheral vasodilation with marked
pooling of blood and a decreased effective
» Necrosis of skeletal and cardiac muscle -
Lowering of body temperature in systemic hypothermia is exacerbated by what? 3
1. high humidity
2. cold wet clothing
When body gets to 90 degrees F, what happens? (3)
1. loss of consciousness
3. atrial fib
What do hypothermic patients do that seems strange?
Want to take clothes off despite freezing
What is frostnip?
cooling, usually of apical structures such as
nose, cheeks and ears, from cold air exposure
What is chilblain?
exposure to damp, non-freezing
temperatures that causes a vasculitis with red, raised
What is immersion foot?
to wet, cool conditions
What is frostbite?
Freezing of tissue
Which is the most severe form of peripheral cold injuries?
Frostbite can lead to ischemia, gangrene and amputation
Direct effects of hypothermia are mediated by what? 2
1. Physical disruption of organelles within the cells
2. High salt concentrations incident to the crystallization of the intra and extracellular water
Indirect effects of hypothermia result from what?
What do they depend on? 2
1. Rate of temp drop
2. Duration of temp drop
Slow chilling induces what? (2)
Leading to what?
2. increased permeability
Rapid chilling induces what? (2)
What happens upon temperature rising?
2. Ischemic injury
Increased permeability with exudation
Electrical injury in the house can be serious when?
If there is low resistance like wet skin, can cause serious injury like ventricular fib
Current from high voltage sources are more likely to produce what? (2)
1. Paralysis of medullary centers
2. Extensive burns
What are two most important variables in electrical injury?
1. Resistance of tissue
2. Intensity of current
Tissue resistance to flow varies how with water content?
Dry skin has greater resistance than wet
Thermal effects of electrical injury depends on what?
intensity of current
What is radiation?
energy that travels in the form of
waves or high-speed particles
Two types of radiation?
Non-ionizing radiation is characterized by what? 3
longer wavelengths, lower
frequencies and lower energy
Ionizing radiaiton can cause what?
typical sources of non-ionizing radiation? 2
Ionizing radiation is characterized by what?
Ionizing radiation will disrupt what?
Examples of ionizing radiation? (5)
1. X rays
2. gamma rays
3. high energy neutrons
4. Alpha particles
5. beta particles
Alpha particles induce what type of damage?
What do they do poorly?
Heavy damage in a certain area
Penetrate poorly due to size
3 ways to measure ionizing radiation units?
1. Amount emitted by source
2. Amount absorbed
3. Effect of radiation
What is a Curie?
It is an expression of what?
Amount of disintegration per second of a radionuclide.
Amount of radiation emitted
What is a Gray?
The energy absorbed by the target tissue per unit mass
What is a Sievert?
Unit of doses that depends on biologic effects of radiation
What areas of the body are most affected by ionizing radiation? 2
Bone marrow and GI
What are the main determinants of biological effect of ionizing radiation?
1. Rate of delivery
2. Field size
3. Cell proliferation
4. Oxygen effects and hypoxia
5. Vascular damage
explain how rate of delivery impacts ionizing radiation effect?
Divided doses allow cells to repair some damage during exposures.
Which recover faster to radiation, normal cells or tumor cells?
Explain how size of field can have effect on ionizing radiation damage?
High doses at small shielded fields = okay
Smaller doses to larger fields = bad
Explain how proliferation can have effect on ionizing radiation damage?
Damages DNA so rapidly dividing cells are vulnerable: Gonads, BM, lymph, mucosa of GI
Cells in what cell cycle stages are most susceptible to ionizing radiation damage?
G2 and M
What is the most important mechanism of radiation damage?
Production of ROS
Which is more sensitive to radiation injury, well vascularized or poorly vascularized tissues?
Well Vascularized (more O2)
Effect of radiation on BV's?
Sclerosis which impairs function
BV change to radiation?
Subintimal fibrosis with narrowing of lumen
Skin changes to radiation?
1. Atrophy of epidermis
2. Hyperkeratosis and hyper/hypopigmentation
How long can squamous and basal cell carcinomas occur after radiation exposure?
Heart changes due to radiation?
Lung changes due to radiation?
Kidney changes due to radiation? 2
2. Hyalinizatin of glomeruli
GI, breast changes due to radiation?