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PBL: Path Ch. 9a Environmental
Terms in this set (171)
What are "Environmental Diseases"?
Conditions caused by exposure to chemical or physical agents in the ambient, workplace, or personal environment (e.g. diet, drugs, alcohol, and tobacco, including diseases of nutritional origin (over- or undernutrition).
What is the single leading global cause of health loss?
What are the leading causes of death in developed countries?
coronary and cerebrovascular diseases
(Thought it was coronary-->cancer-->cerebrovascular dz???)
What are the major risk factors of coronary and cerebrovascular diseases?
obesity, smoking, and high cholesterol
5 of the top 10 causes of death in developing countries are what?
Malnutrition increases the risk of?
During the post-natal period about 50% of all deaths in children younger than 5 are associated with what three conditions?
2. Diarrheal dzs
What strains of pathogens are the most important clinically?
drug resistant strains
What type of diseases constitute almost a 1/3 of newly emerging infections, and in many cases can be linked to environmental changes, including global warming?
How will global warming effect health? (4 points)
cardiovascular and respiratory disease will amplify
gastroenteritis and infection epidemics
increase in vector borne infectious diseases
malnutrition will increase
What is toxicology?
The study of distribution, effects and mechanisms of action of toxic agents.
T/F Toxicity of a poision is based upon the dosage
What are xenobiotics?
Exogenous agents in the environment that may be inhaled, ingested, or directly absorbed.
Lipophilic compounds, such as most solvents and drugs, have ____ blood transport and will cross plasma membranes more readily
Processes that occur in phase I vs. phase II metabolism
Phase I: Reduction, oxidation, hydrolysis with cytochrome P-450
Phase II: Conjugation via
ulfation to water-soluble compounds by combination with glutathione so they can be easily excreted
Drug-metabolizing enzymes are divided into two general groups. What are they?
What is the most important Phase I drug metabolizing enzyme?
(Hint: Mostly located in the ER of liver, but can also be found in skin, lungs, GI, and other organs)
Most important enzyme: cytochrome P450
What is the negative side-effect of Phase I rxns?
(Hint: They can go on an cause cellular damage)
releases oxygen derived free radicals
CYPs are the pro- duction of the toxic trichloromethyl free radical from carbon tetrachloride in the liver, and the generation of a DNA-binding metabolite from benzo[a]pyrene, a car- cinogen present in cigarette smoke
do the following increase or decrease CYP activity:
Smoking, alcohol, and hormones
(Hint: They bind to nuclear receptors which then heterodimerize the retinioc X receptor which then associated with the 5' promoter region)
does the following increase or decrease CYP activity:
Decreased, thus allowing other drug levels in the body to rise.
What is the major organ effected by outdoor air pollution?
lungs (can also go on to effect other organs of the body)
What are the common effects of outdoor air pollution?
Decreased pulmonary function, lung inflammation, increased airway reactivity, diminished mucocilliary clearance, and increased infections.
How does ozone form? How is it good?
Forms from the interaction of oxygen and ultraviolet radiation. Stratospheric ozone is critical in absorbing solar UV radiation.
What depletes ozone?
Ozone depletion is associated with increases in cancer in this organ?
It increases skin cancer risk. Less Ozone to block UV radiation
Ozone in the lower stratosphere is a major component of what?
Ozone toxicity is due to the production of what?
free radicals, thus causing injury to the alveolar epithelium (type I alveolar cells) causing the release of inflammatory mediators and symptoms of upper respiratory inflammation
How is sulfer dioxide produced?
the combustion of coal and oil, copper smelting and paper manufacturing
What is suffer dioxide converted into?
what are the effects?
sulfuric acid and suffer trioxide;
burning, dyspnea, airway hyperactivity
What is particulate matter also known as?
Particulates smaller than ____are the most deleterious due to being phagocytosed by macrophages and neutrophils causing the release of inflammatory mediators
What is a colorless, odorless, tasteless, non-irritating gas produced by incomplete oxidation of carbonaceous materials?
Acute lethality of CO occurs through (big picture)?
CNS depression and systemic hypoxia
Acute CO poisoning is characterized by a cherry-red coloring of the victim due to high levels of this in the blood?
What is the value of Hb saturation at which systemic hypoxia develops w/ CO?
What parts of the brain are most effected by the ischemic effects of the stable carboxyhemoglobin?
Basal ganglia and lenticular nuclei
What is the value of Hb saturation at which unconsciousness and death develops w/CO?
60 to 70% saturation
What are some of the major indoor air pollutants?
wood smoke (May predispose to lung infection, and can contain polycyclic hydrocarbons)
bioaerosols (distressing allergens + microbial agents capable of causing infectious dz)
radon (derived from uranium): lung cancer in uranium miners
formaldehyde: used in the manufacture of buildings, and can cause breathing difficulties, trigger asthma attacks, and cause a burning sensation in the eyes and throat in poorly ventilated homes. Carcinogen for animals and humans.
Lead, frequently found in old house paints and in manufacturing of batteries/pigments/car radiators/tin cans, competes with what ion in the body?
(Hint: Can lead to hematolgic, skeletal, neurologic, GI, and renal toxicities)
85% of the lead accumulates in what organs to compete for calcium
bones and teeth
Who is at more risk for lead poisoning: kids or adults?
Children bc they absorb more than 50% of ingested lead (compared with ≤15% in adults); the higher intestinal absorption and the more permeable blood-brain barrier of children create a high susceptibility to brain damage. Can present as sensory, motor, intellectual and psychologic impairments.
How is lead toxic to neurons?
Neurotoxicity - altered calcium homeostasis and neurotransmitter release
T/F CNS disturbances due to lead toxicity are seen in both kids and adults, but peripheral demylinating neuropathies of the motor nerves predominate in adults
What muscles of the wrist and fingers are most often first affected by lead posioning?
(Hint: Presents as wrist drop)
Extensor muscles of the wrist
(Followed by paralysis of the peroneal muscles presenting as foot drop)
How is lead toxic to blood?
inhibition of enzymes involved in heme synthesis and iron incorporation
How is lead toxic to bones and cartilage?
altered cartilage remodeling in epiphyses and inhibition of bone healing by increasing chrongenesis and delaying cartilage mineralization
Can result in increase bone density detected as radiodense "lead lines"
What two enzymes involved in heme synthesis are inhibited by lead?
1. δ-aminolevulinic acid dehydratase
2. ferrochelatase: catalyzes the incorporation of iron into protoporphyrin, and its inhibition causes a rise in protoporphyrin levels.
What type of RBCs can be seen due to inhibition of ferrochelatase by iron?
Ringed-sideroblasts: Iron-laden mitochondria, which can be detected by Prussian blue stain
Punctate basophilic stippling of the red cells.
What type of anemia is caused by heme deficiency?
(Hint: hemoglobin synthesis is inhibited)
microcytic hypochromic anemia
How is lead toxic to GI system?
abdominal pain and anorexia (lead colic)
What part of the kidney is typically affected due to lead poisoning?
(Hint: Intra-nuclear inclusions consisting of protein aggregates will be present, potentially leading to interstitial fibrosis of the kidney and decreased uric acid excretion which may precipiate gout)
Proximal convoluted tubule
T/F Both mercury and lead can lead to damage of the CNS and kidney
Is mercury water soluble? How does its solubility enhance toxicity?
No, it is lipid soluble. This allows it to accumulate in the CNS.
What are the (3) major means of exposure to mercury?
Major cause: methyl mercury contaminated fish (Swordfish, shark, bluefish)
dental amalgams vapors
gold mining; water run off
Methyl mercury-induced toxcitity seen in utero resulting cerebral palsy, deafness, blindness, mental retardation, and major CNS defects.
Developing brain is extremely sensitive to methyl mercury
Mercury toxicity is related to high binding affinity for cellular ___ groups.
What is the body's main protective mechanism agaisnt mercury-induced CNS and kidney damage?
(Hint: Donates a sulfhydryl group)
What systems of the body is arsenic most toxic to?
What forms of arsenic are most toxic?
trivalent; arsenic trioxide and sodium arsenite
Where is arsenic naturally found?
FF: Also used as a wood preserver and herbicides in agriculture
soil and water
Which form of arsenic is a fronline treatment for acute promyleocytic leukemia?
Cadmium is generated by what?
mining, electroplating, and the production and improper disposal of nickel cadmium batteries.
Arsenic inhibits what ATP generating pathway?
mitochondrial oxidative phosphorylation by replaces the phopsphates in ATP
Chronic exposure to arsenic increases the risk of what three types of cancer (general)?
Lungs, bladder, and skin.
T/F The arsenic-induced skin tumors differ from those induced by sun bc they are often multiple and usually appear on the palms and soles
What mechanism of DNA repair is thought to be affected by arsenic in the lungs ?
Nucleotide excision repair
What two parts of the body are particularly susceptible to cadmium due to the formation of ROS?
What is the most common route of cadmium exposure?
ingestion of contaminated food
What is the transporter cadmium used to to be taken up into cells?
(Hint: Normally a transporter for zinc)
More than ___ injuries and ____ deaths annually in the US are due to work related illness or accident.
10 million and 100,000
Cadmium toxicity leads to what in the lungs?
alveolar macrophage necrosis, causing
obstructive lung disease
and renal tubular damage that may progress to end-stage renal dz
Can increase the risk for lung CA
Which of the following is associated with leukemia due to chronic exposure? Select all that apply.
E. 1-3 butadiene
Hint: Commonly seen in rubber workers
E. 1-3 butadiene
What CYP in the liver metabolizes benzene causing a dysfxn of differentation of hematopiotic cells in the bone marrow, thus increasing the risk for acute myeloid leukemia?
Polycyclic hydrocarbons are potent carcinogens associated with tar+soot, and the combustion of fossil fuels, and are associated with increased risk of ____ and ____ cancers.
lung and bladder
What type of CA is commonly associated with tar and soot?
(Hint: Chimney sweeps)
Most organochlorines have what effects?
endocrine disrupters, alter drug metabolism
What are some examples of organochlorines, halogenated organic compounds that resist degradation?
dichlorodiphenyltrichloroethane (DDT) (a pesticide)
polychlorinated biphenyls (PCBs)
Inhalation of ___________ can cause chronic, non-neoplastic but diffusely fibrosing pneumoconioses
(Hint: Examples are coal, silica, asbestos, and asbestosis)
Vinyl chloride monomers used to produce polyvinyl chloride resins are associated with _____ of the liver, which is a very very uncommon tumor of the liver
What is used plasticizer in flexible plastic products and epoxy resins that can potentially cause endocrine disruption and testicular dysgenesis?
(Hint: Infants are more suseceptible)
What is the most readily preventable cause of death in humans?
(HInt: responsible for more than 400,000 deaths annually in the US and 5 million deaths worldwide commonly due to cardiovascular dz)
What type of cancer can smokeless tobacco cause?
What is the most common cause of human malignancy, responsible for over 90% of lung cancers
What 3 diseases account for for the vast majority of mortality associated with smoking?
chronic pulmonary disease
T/F Smoking cessation can reduce the risk of overall mortality within 5 years of stop
Lung CA mortality decreased by 21%
What are 3 of the potent carcinogens in cigarette smoke?
What does nicotine do to the body?
binds to CNS nicotinic Ach receptors for catecholamines that increase heart rate, blood pressure, and cardiac contractility
What are the 2 carcinogens mostly responsible for the development of lung CA?
(Hint: Can form DNA adducts that persist and cause mutations in oncogenes and tumor suppressors)
smoke and smokeless tobacco both interact with alcohol in potentiating what cancer?
Besides, the lung cigarette smoking contributes to cancer development in which areas?
Cigarette smoking is strongly linked to development of what cardiovascular disease which in turn increases the risk of this major life threatening event ?
(Hint: Increased platelet aggregation, decreases the myocardial oxygen supply, increases the oxygen demand, and decreases the threshold for V-fib)
atherosclerosis and myocardial infarction
Smoking increases the amount _______________________ in the lung, the cells causing responsible for elastase production increasing the risk for emphysema
Lung cancer due to second hand smoke is ___ times greater than in individuals not exposed to environmental smoke.
How does maternal smoking effect the fetus?
Causes fetal hypoxia increasing the risk of intrauterine growth retardation
increased risk of spontaneous abortion and preterm birth
How many alcoholic are there in the US?
What is measured in the blood to asses passive smoke inhalation of non-smokers?
(Hint: metabolite of nicotine)
How many deaths each year are attributable to alcohol abuse?
15% of alcohol related deaths are due to what disease process?
The blood alcohol concentration of ____ is the legal definition for drunk driving in most states
What levels of alcohol are associated with stupor and coma?
Alcohol leads to what accumulating in the liver?
liver fat accumulation
What metabolite is directly responsible for most of the toxic and chronic effects of ethanol?
(Hint: Associated with oral cancers due to the formation of DNA adducts)
Alcohol is absorbed where in the GI tract?
stomach and small bowel; unaltered
What are the symptoms of acute alcohol injury?
hepatic steatosis (fatty change)
gastritis and ulceration
depression of CNS activity
Chronic alcoholism effects which organs, with substantial morbidity and mortality?
all of them
How does alcohol effect the GI tract?
acute gastritis and ulceration may cause massive bleeding or it may be a result of portal hypertension and esophageal varicies
What is the main site of injury in alcohol injury mostly due to acetaldehyde?
what does it result in?
alcoholic hepatitis and cirrhosis
What is the CYP involved in the microsomal oxidation system of alcohol?
(Hint: Located in smooth ER)
What does the production of ROS by CYPE21 cause to the hepatocyte?
lipid peroxidation of hepatocyte cell membranes.
T/F Alcohol causes the release of endotoxin (lipopolysaccharide) from gram negative bacteria in the intestinal flora, which stimulates the production of TNF from the macrophages and Kuppfer cells leading to hepatic injury
How does alcohol potentiate the effects of CYP2E1 substrates?
Delays drug catabolism; thereby, potentiating the depressive effects of narcotic, sedative, and pyshoactive drugs
CYP inhibition vs. induction:
• If inhibited--> drug levels rise
• If induced-->drug levels fall
I don't understand this then:
alcohol induces CYP2E in the liver, toxicity can occur at lower doses in chronic alcoholics.
What is the allelic variation of ALD that leads individuals unable to oxidize acetaldehyde presenting with symptoms of nausea, flushing, tachycardia, and hyperventilation of alcohol consumption?
Alcohol abuse can lead to a deficiency in what, which can lead to what syndrome?
thiamine (poor nutrition)
During what trimester of pregnancy is alcohol consumption most likely to result in fetal alcohol syndrome?
Hormonal replacement therapy increases the risk of what two disease processes?
breast cancer and thromboembolism
How is moderate alcohol consumption thought to be protective against coronary artery dz?
Increase high-density lipoprotein (HDL) levels
inhibit platelet aggregation
Lower fibrinogen levels,
What effect does the tetracylcine derivate have on the skin?
XS skin pigmentation
What does warfarin vs. dabigatran inhibit?
Warfarin is an antagonist of vitamin K
Dabigatran is a direct inhibitor of thrombin that can be used to thrombotic stroke in those with A-fib
T/F HRT in females is associated with a decreased risk of osteoporosis
T/F Combination estrogen-progestin increases the risk of breast cancer while estrogen alone in women with hysterectomy is associated with a borderline reduction in risk of breast cancer.
T/F MHT may have a protective effect on the development of atherosclerosis and coronary disease in women younger than age 60 years, but there is no protection in women who started MHT at an older age.
Oral contraceptives are associated with increased:
(venous thrombosis and pulmonary embolism) bc of the increased synthesis of coag factors
cardiovascular disease in those women older than 35 who smoke
cancer (cervical in those with HPV)
Large and solitary tumor with a well-encpasulated mass
T/F OCPs use is not associated with increased risk for breast CA, endometrial CA, or ovarian CA
(Idk how bc i thought estrogen exposure increased risk for them)
In which subset of population do OCPs increase the risk of cervical carcinoma?
Those with HPV
High doses of anabolic steroids in males, inhibits LH and FSH production and lead to ______, which leads to increased estrogens and _____.
T/F Hepatic cholestasis may develop in those taking oral anabolic steroids
Decrease in bile flow due to impaired secretion by hepatocytes or to obstruction of bile flow through intra-or extrahepatic bile ducts.
What is responsible for more than 50% of acute liver failure cases in the US, with 30% mortality.
What is the most commonly used analgesic in the US?
(Hint: Overdoses of it can lead to centrilobular necrosis)
At therapeutic doses more than 95% of acetaminophen is metabolized by what what phase of hepatic enzymes?
What is acetylsalicylic acid?
Long term ingestion (years) of analgesic mixtures of aspirin and phenacetin is associated with what kidney problems?
renal papillary necrosis
Is there physical dependence with cocaine?
Cocaine is extracted from this leaf.
Heroine is an alkaloid from this plant.
Is heroine physically addictive?
Name two amphetamines
MDMA - 3,4 methylenedioxymethamphetamine (ecstasy)
Marijuana is isolated from this hemp plant
What is the major psychoactive substance found in marajuana?
Delta 9 -tetrahydrocannibinol (THC)
This drug (______) binds to _____receptors that modulate the hypothalamic-pituitary-adrenal axis and regulates appetite, food intake, energy balance, fertility, and sexual behavior.
What is an abrasion?
a superficial wound produced by rubbing or scraping
What is a contusion?
a blunt force trauma that injures small blood vessels and causes interstitial bleeding, usually without disruption of the continuity of the tissue (bruise)
What is an incision?
inflicted by a sharp instrument that cuts vessels and leaves relatively smooth edges
What is a laceration?
a tear or disruptive stretching caused by blunt trauma; as opposed to an incision, lacerations typically have intact bridging blood vessels and jagged irregular edges
What is a puncture?
trauma caused by a long, narrow instrument or gunshot
What is penetrating puncture?
when tissue is only pierced
What is a perforating puncture?
when the tissue is traversed to create an exit wound
The clinical significance of burns depends on what 4 factors?
Depth of the burn
Percentage of body surface involved
Internal injuries from inhalation of hot and toxic fumes
Promptness and efficacy of post burn therapy
What is hyperthermia?
prolonged exposure to elevated ambient temperatures
Hyperthermia can lead to (3 things)?
What is the most common heat syndrome?
Explain what happens in heat exhaustion.
failure of the cardiovascular system to compensate for hypovolemia, second to water depletion.
Mutations in what receptor can cause malignant hyperthermia?
ryanodine receptor type I - responsible for regulating skeletal muscle sarcoplasmic reticulum calcium release
What is hypothermia?
prolonged exposure to low ambient temperature
At what core body temperature does an individual lose consciousness, followed by bradycardia, and atrial fibrillation?
90 degrees F
What are 3 variables are associated with electrical injury?
What type of current induces titanic muscle spasm and can prolong the duration of exposure to electrical injury by causing involuntary clutching?
The greater the tissue resistance, the greater the heat generated. Tissue resistance to electrical injury varies inversely with water content. Is dry or wet skin more resistant to electrical current?
dry skin is resistant, wet skin has greatly decreased resistance
What is radiation?
energy traveling in the form of waves or high-speed particles; spans the electromagnetic spectrum
What are the two types of radiation?
What are examples of non-ionizing radiation?
UV, infrared light, radio waves, microwaves and sound waves
What are the characteristics of non-ionizing radiation?
Relatively longer wavelengths
Can produce vibrations and rotation of atoms but have insufficient energy to displace bound electrons
What are examples of ionizing radiation?
High energy neutrons
Alpha particles (two neutrons and two protons)
Beta particles (essentially electrons)
What are the characteristics of ionizing radiation?
Sufficient energy to remove electrons from biologic molecules
What are the main determinants of the biological effects of ionizing radiation?
Rate of delivery
Field of size
Cell proliferation - rapidly dividing cells are more susceptible than quiescent cells
Oxygen effects and hypoxia - water ionization creates reactive oxygen species
Vascular damage - endothelial cells are moderately sensitive to radiation injury
Whole body exposure to 1 Sv of radiation produces little effect. True of false.
True. Greater exposures can lead to acute radiation syndromes and higher doses can lead to peripheral lymphopenia with spleen and lymph node atrophy.
Very high doses of radiation can cause permanent aplastic anemia. true or false.
True.very high doses of radiation can kill hematopoietic stem cells.
What is a common response to radiation therapy in the radiation field, weeks to months following treatment.
Fibrosis, as a consequence of replacing dead tissue with scar.
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