Exam 2 Flashcards
What are the four routes of exposure?
- Ingestion
- Inhalation
- dermal
- Injection
What are the steps of exposure?
Step 0-Exposure: Step 1- Delivery Step 2- Reaction Step 3- Dysfunction Step 4- Repair or failure to Repair
What is the first pass elimination?
Its the hiesman move of the cellular level. I redirects chemicals away from the target organs and prevents toxicity
What factors influence whether or not a chemical/toxicant is absorbed?
its solubility
What is the most important chemical property influencing absorption?
Concentration, Surface area of exposure.
What are the Characteristics of epithelial layer
lipid soluble, nonpolar, hydrophobic
What are the properties of a hydrophilic molecules?
water soluble
Charged ( Polar)
like mixes with like( Polar with polar)
Water mixes with polar molecules
water is a what type molecule?
Polar
What are properties of a hydrophobic molecule?
Not water soluble
Oils( Lipids) are examples of nonpolar molecules
Ex: Oil and water do not mix by themselves
Whats an example of a mix of Polar and Nonpolar?
Soap micelle
What are the Properties of Soap Micelle?
Polar on outside
Nonpolar on the inside
What is Passive Transport?
diffusion from high to low concentration
where No energy required
No ATP necessary
What is Facilitated Diffusion?
Channels through membrane that allow diffusion down the gradient from high to low concentration ( no ATP recessary
What is Active Transport?
ATP is required
It transports up the gradient from low to high concentration
Most toxicants cross the membranes by _______
Simple Diffusion
Rate of diffusion depends upon what three things?
- Lipid Solubility
- Molecular Size
- pKa
PC of 10 is very______
Lipophilic
PC of 0.1 is _______?
hydrophilic
What is PC?
Partition Coefficient
What is PC?
is a measure of the substance in a lipid over an aqueos solution
Describe pKa
toxins is 50% charged and 50% uncharged
Scale of 0-14
What are examples of specialized barriers
- Blood Brain Barrier
- Placental
- Blood-testis
- Oocyte
what are the leaky capillaries?
Liver & Kidneys
What chemicals are most likely to be absorbed?
Lipid Solubile
What is A-D-M-E
Absorption- Site of entry
Distribution- Travels through the bloodstream
Metabolism- Transformation of chemical
Excretion- Removal from the body
What are the factors for absorption?
Lipid Solubility
Molecular Size
Site
Stability at stomach
Reabsorption like absorption is most dependent upon what property of the toxicant or metabolite?
Lipophilic
Lipid Soluble
Hydrophobic
What is Biotransformation?
Biochemical process that converts lipophilic compounds usually though enzymatic action in hydrophilic metabolites
What Organs have biotransformation
Liver-High
Kidneys-Medium
Skin,testes- Low
Cellular Sites: Microsomes, mitochondria, Cytosol,, Nucleus
Absorption by skin is_______
Passive diffusion
Absorption by skin does?
Lipid soluble substances will penetrate the dermal barrier
Biotransformation does what?
Chemical mechanism for eliminating a toxicant
Does biotransformation require energy?
Yes, it requires energy or energy equivalents
What are factors affecting biotransformation>
Inhibition and induction Age Sex Hormones Pregnancy Diet Disease Genetics Circadian rhythms
Most organs including the blood have what?
Biotransformation capacity
What is Phase 1
Phase 1 converts lipophilic compounds into hydrophilic compounds
- Increases water solubility
- Decrease the renal tublar and intestinal reabsorption of the products
What are some Phase 1 Reactions?
the are catabolic or breakdown reactions ( Oxidation, reduction and hydrolysis)
May occasionally prodcuse metabolites that are somewhat more water-soluble than the parent
What is Phase 2?
Conjugation of chemical into a new chemical
Requires energy and cofactor
Makes hydrophilic compunds
What class/family of enzymes is most responsible for most toxication and detoxication of metabolites and toxicants?
Cytochrome p450
Cytochrome p450 attempts to decrease the toxicity of compounds by adding endogenous acids to make the compounds of interest more or less hydrophilic?
More Hyrophilic
Chemical compounds that can be dissolved in plasma water are the chemicals most easily excreted via aqueous urine. What is the most important chemical property of these chemicals that are most freely soluble in aqueous urine.
Hydrophilic
Highly Lipophilic compounds are not efficiently removed, but some may be eliminated from the body via the________?
mammary gland in milk lipids
What is the process of self-programmed cell death?
Apoptosis
What is the process of uncontrolled cell swelling until cell lysis?
Necrosis
______a sufficient amount of the____molecule, the cell will not be able to power the pumps required for pumping out calcium and ensuring a proper concentration gradient for removing harmful chemicals? The consequence of this build-up of harmful materials inside the cell results in
Without
ATP
Cell Necrosis
What are the mechanisms of Toxic Cell Death?
Primary metabolic disorders jeopardizing cell survival
- ATP depletion
- Ca2+ Accumulation
- ROS ( reactive oxygen species) and RNS( reactive nitrogen species) generation
When cells die-off by either apoptosis or necrosis, the body has a mechanism of cell replenishment by cell division/replication. This process is called…
Mitosis
A life-time of lung or liver damage can lead to tremendous scarring/connective tissue in these organs… we call this process what?
Fibrosis
What are the Non-stochastic effects are threshold type effects
effects which increase in severity with increasing dose
Stochastic effects are non-threshold effects
effects which increase in severity with increasing dose)
That is, the severity of stochastic effects do not depend on the dose
Who is Ramizzini
Father of occupational medicine
Wrote Diseases of Workers
Breast Cancer in Nuns associated with celibacy
Who Percival Pott?
Scrotal cancer in chimney sweeps
What was the cancer causing agent Percival pott discovered?
PAH ( Polcyclic aromatic hydrocarbons)
Who was Rehn
discovered Aniline ( textile dye) associated with bladder cancer
Who was Layne Claypon?
He had a role of reproductive experience in the etiology of breast cancer
Lowen, Goldstiend & Gernhardt discovered what?
Cigarette smoking and lung cancer
Who was Richard Doll?
World’s leading cancer is epidemiologist
20,000 male physicians studied since the 1950’s to assess health effects of cigarette smoking and other exposures.
Grilled meats were associated with what?
Colon cancer due to partial burn products ( ROS/RNS)
What were the changes over time in the US population causes of death?
1900’s- tuberculosis, pneumonia/ influenza
2010- cancer and heart disease
Cancer may remain dormant for years after the causal event:_____
Remission
Cancer is a what?
Neoplasm( New Growth)
Process in which cells undergo some change that renders them abnormal causing uncontrolled growth that causes them to spread
Cancerous tissue may invade and destroy normal tissues but ___________
Lack inhhibition
How long (duration/time) are carcinogenicity assays?
Limited in vivo bioassays
a. Designed to evaluate carcinogenic potential within a relatively short period of time (40 weeks or less)
In vivo stands for?
In a living organism
In vitro stands for?
simulated in a lab container like a test tube
A1 is what type of cancer?
Confirmed human carcinogens
A2 is what type of cancer?
Suspected human carcinogens
A3 is what type of cancer?
Confirmed animal carcinogens with unknown relevance to humans
A4 is what type of cancer?
Not classified as a human carcinogen
Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of lack of data.
A5 is what type of cancer?
Not suspected as a human carcinogen based on properly conducted human epidemiologic studies
What is the differentiate in malignant and benign?
Critical difference is the ability o metastasize
What are the three steps required in carcinogenesis?
Initiation
Promotion
Progression
What is Initation-
Results from a simple mutation in one or more cellular genes controlling key regulatory pathways of the cell
What is Promotion
Results from the selective functional enhancement of signal transduction pathways induced in the initiated cell and its progeny by the continuous exposure to a promoting agent
What is Progression
Results from the continuing evolution of a basically unstable karyotype
what is Aplasia?
A developmental defect in which there is a complete or almost complete failure of a tissue or organ to develop
What is hypoplasia
A developmental defect in which there is a complete or almost complete failure of a tissue or organ to develop to full size
what is Atrophy?
A decrease in tissue or organ size that may result from a decrease in cell size, cell number or both
what are the three terms related to changes in tissues and organs smaller then normal?
Aplasia
Hypoplasia
Atrophy
What are the terms related to changes in tissues or organs larger than normal?
Hypertrohpy
Hyperplasia
what is Hypertrophy?
INcrease organ size by increase cell size
What is Hyperplasia?
Increased organ or tissue size due to increase in cell number
Define carcinogen
Any chemical capable of producing an increased number of tumors in some test species
What Cancer comes from PAH?
Skin and lung cancer
What is a Co-carcinogen?
A chemical that increases the carcinogenic activity of another carcinogen when co-administered
What cancer causing agent is related to Co-carcinogen?
Asbestos & Cigarette smoke
What is an Initiator?
A chemical that induces the cainogenic process in a cell or tissue
An agent that causes cells to mutate( Ex: Asbestos)
What is Promoter
A chemical that can increase the incidence of response to a carcinogen preiosly administered
An agent which stimulates cancer cells to grow faster (Example DDT pesticide)
c. Example: 2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD) aka dioxins
What is a Progressor?
A chemical capable of converting an initiated cell or a cell ion he stage of promotion potentially malignant cell
What is a Complete carcinogen?
A chemical possessing the capability of inducing cancer from normal cells
Asbestos and mesothelioma type cancer
What are two dunfamental defense mechanisms against a carcinogen?
DNA repair of mutations/damage during initiation phase
Apoptosis of cell in the event of DNA repair is unsuccessful
Replacement o cells lost by mitosis of stem cells
How do they monitor/prevent radiation exposure in workplace environments… like hosptials?
a. Personally Worn Radiation Dose Badges
Common radiation hazard from inhalation in Kentucky
Radon
What is Radon
Comes from naturally occurring uranium that radioactively decays in bedrock to radon gas that enters through the slab imperfections in basements.
Safe/Acceptable risk level for this hazard in homes?
According to Environmental Protection Agency: Less than 4 picoCuries/Liter of air
Pressurization or depressurization is important for reducing the concentration of this agent in the home?
Sub-slab depressurization is done using a hole like those used for sump pumps with a tube and air fan that exhausts radon out the roof.
List four carcinogens that can be inhaled?
(Wood dust, silica dust, PAHs, Asbestos fibers, Coal tar pitch derivatives
What are common Carcinogens?
a. Benzene: causes Leukemia
b. Chloroform: Liver cancer
