What are substances found in food, give an example of each.
nutrient substances (natural compounds proteins, fats, carbohydrates)
non-nutrient substances (food additives, plant hormones, pesticides)
is a complex mixture of compounds that can be all natural, processed or both
food
examples of nutrient substances
carbohydrates
proteins
fats
vitamins/minerals
examples of non nutrient substances
pesticides
food additives (color, flavor)
plant hormones
two major ways food causes toxicity
adverse and allergic reactions to food
ingestion of food containing toxic substances
what are the 5 types of adverse/allergy reactions
food hypersensitivity
food idiosyncrasies
anaphylactoid reactions
pharmacological food reactions
metabolic food reaction
characteristics of food hypersensitivity
immediate immune response with cutaneous reaction or anaphylaxis
example of food hypersensitivity
allergic response to proteins in milk, egg whites, egg yolk, or peanuts
characteristics of food idiosyncrasies
abnormal response to food additive or food substance similar to food hypersensitivity but DO NOT involve the immune system
examples of food idiosyncrasies
smelly urine caused by asparagus (inability to metabolize methanthiol)
abdominal pain with milk (lactase deficiency)
migraine with chocolate
characteristics of anaphylactoid reactions
mimic anaphylaxis but occurs through the DIRECT application of histamine
examples of anaphylactoid reactions
fish spiked with histamines cause headaches or histamine poisoning
sulfate sensitivity causes asthma
cheese
characteristics of pharmacological food reactions
exaggerated responses to pharmacological agents in food
might be due to receptor sensitization
characteristics of metabolic food reactions
characterized by toxic effects of food eaten in excess or foods not processed correctly
what is the most common symptom for food hypersensitivity
cutaneous reactions or anaphylaxis
what is the difference between food hypersensitivity and food idiosyncrasy
food hypersensitivity is through an immune response
what is an example of food idiosyncrasy
smelly urine from asparagus via the inability to metabolize methanthiol
lactase deficiency causing abdominal pain with milk
how does an anaphylactoid work and what are examples
anaphylactoids directly apply histamines to produce anaphylaxis-like reactions
fish- histamine poisoning and headaches
sulfate sensitivity-deficiency to metabolize sulfate
cheese-histamine poisoning
what are three fish toxins
domoic acid
tetrodoxin
brevetoxin
toxic mechanism of domoic acid
analog to glutamine that causes the uncontrolled release of GABA causing an inhibitory response with hippocampal damage
found in shellfish
toxic mechanism of tetrodoxin
present in pufferfish
blocks cation movement causing cellular arrest and paralysis
toxic mechanism of brevetoxin
found in filter feeders
binds to voltage-dependent sodium channels causing tingling and loss of motor control
example of microbial toxin
botulism
toxic mechanism of botulism
produced from bacteria in improperly canned foods
dysregulates acetylcholine function at peripheral nerve endings primarily targeting respiratory system = respiratory failure
describe mad cow disease
transmitted by prions that function as neurotoxins causing neurological deterioration resulting in death
what are the three major classes of outdoor pollutants
classic reducing type
particulate matter
photochemicals
what are classic reducing type outdoor pollutants characterized by
sulfur dioxide and smoke exposure
what are particulate matters characterized
their composition of solid/liquid organic and inorganic compounds
what are photochemicals characterized by
their arise from series of reactions in the troposhere activated by UV spectrum of sunlight
how does sulfur dioxide react in the body once inhaled?
it stimulates mucus secretion and bronchoconstriction by dissolving in the surface lining fluid of lungs and turned into sulfite/bisulfite and is readily distributed
how are particulate matters primarily released
through emissions
what do particulate matters involve
conversion of gas to particles
what substances are included in particulate matters and give an example
metals- zinc, nickel, iron,
carbon particles- diesel particles
how do ozone and nitrogen differ? which is more reactive and where are they found?
ozone is highly reactive and more toxic and is found at Earth's surface and smog
nitrogen is heaver and is found at levels near the ground; causes pulmonary edema and puts farmers that ferment silage at risk
who is at most risk for nitrogen dioxide toxicity
farmers who ferment silage
what pathologies are associated with nitrogen dioxide
pulmonary edema
list the clinical stages for poisoning treatment in order
stabilize the patient
perform a complete clinical evaluation
prevent further absorption in the body
enhance toxic agent elimination process
administer antidote (if available)
care and follow up
when stabilizing a patient what three assessments need to be performed
assess airway, respiration, and circulation
list the 4 different clinical evaluations conducted
medical history
physical exam
laboratory evaluation
radiographic evaluation
what is the goal in determining medical history
determine the toxic agent
identify exposure route and duration
when unknown, the highest dose is assumed
what is the goal in a physical examination
determine patient's mental status, condition,
possible trauma, or identify any identifiable toxicological signs of a specific agent (i.e. arsenic accumulation in nails)
what is the goal of a laboratory exam
determine the concentration of a toxic agent in the blood
what is the goal of a radiographic evaluation
visualize ingestoin
can detect ferrous and potassium salts, lead, and halogenated compounds
CTs of head and chest/abdomen x-ray
CT for carbon monoxide to determine severity of poisoning via brain lesions
what is the goal in the prevention of poison absorption
prevent as much poison from being absorbed into the circulatory system
what are the 3 different types of exposures in clinical toxicology
inhalation
topical
oral
how is inhalation exposure prevented
removing patient from area of exposure
set in a well ventilated area
oxygenation of patient
how is topical exposure prevented
removal of clothes that were exposed and full wash of exposed skin with mild soap
how is oral exposure prevented
activated charcoal
bowel irrigation gastric lavage
what is the key/ direct association with successful prevention of inhalation of toxic agent
pulmonary first pass elimination
describe the use of activated charcoal in oral exposure prevention
it is the first immediate treatment used as it readily absorbs toxins in the body
describe the use of bowel irrigation in oral exposure prevention
it is performed when toxins are still present in the bowels
describe the use of a gastric lavage in oral exposure prevention
orogastric tube is inserted into the stomach to flush the system with water while aspirating the fluid out until the toxic agent is removed
what is the goal of enhancement of poison elimination
eliminate the poison once it has reached the circulatory system
what are ways to enhance poison elimination
alkalization
dialysis
hemoperfusion
hemofiltration
plasma/blood transfusion
activated charcoal
describe alkalization
ion trapping; pH of urinary filtrate is increased so that weak acids are prevented from being reabsorbed
describe dialysis
used to eliminate methanol, ethanol, isopropanol, and ethylene glycol
describe hemoperfusion
blood is pumped through a perfusion cartridge where it interacts with activated charcoals to absorb toxins from the blood
describe hemofiltration
blood plasma is filtered and removed from blood using hydrostatic pressure to help remove toxins
describe plasma/blood transfusions
used to remove plasma protein-bound toxins and high molecular weight toxins
describe activated charcoal use
allows for the systemic clearance of toxins as it readily absorbs toxins from the body
3 main goals for making/ using antidotes
agents that specifically bind to toxic agents
agent that antagonize the effects of toxic agents
agent that chemically interacts with toxins to increase the detox process
what is an example of antidotes that specifically bind to toxic agents
chelating agents bind to metals and ions so that they are no longer harmful in the body
what is an example of antidotes that antagonize the effects of toxic agents
atropine is used for exposure to organophosphate poisoning prevents accumulation of acetylcholine in muscarinic and acetylcholingeric receptors
what is an example of antidotes that chemically interacts with toxic agents to increase the detoxification process
sodium nitrite used for cyanide poisoning; it increases the formation of methemoglobins that serve as an alternative binding site for cyanide
still requires secondary treatment
why is it important to do care and follow up after treatment?
some poisons have delayed toxicity
toxins can have multi-phase toxicities
psychiatric changes can result from exposure to toxic agents or patient needs to be monitored for self-harm
sources of developmental toxicants in infants
radiation
infections
maternal trauma and metabolic imbalances
drugs and chemicals
types of adverse outcomes during pregnancies
post-implantation pregnancy loss (31%)
neurologic dysfunction (17%)
minor birth defects (14%)
low birth weight (7%)
major birth defects at birth (3%) 7% at 1 year
infant death (1.4%)
how many pregnancies end in normal, healthy births
less than 50%
what are the 4 manifestations of abnormal development
death
malformation
growth retardation
functional deficits
what are the six principles of developmental toxicity
susceptibility on teratogenesis is dependent on genotype and environmental factors
varies with developmental stage and which exposed to
agents follow a specific mechanism to cause developmental issues
agent accessibility is dependent on the route of expos
what is the difference between low dose and high dose embryonic exposure
low doses cause growth retardation and high doses cause embryo lethality
what are the major effects of prenatal exposure to toxins
embryo lethality
malformations
growth retardation
what do all developmental toxicities result in
insults to the embryo at the cellular level either directly, indirectly through the mother or placenta or a combination
ways in which developmental toxicities affect the embryo at the cellular level
directly, indirectly through the mother or placenta or a combination
maternal factors that affect development
genetics
disease
nutrition
stress
placental toxicity
maternal toxicity
how can maternal genetics affect development
the genetic make up of the mother is a risk factor
how can maternal disease affect development
uncontrolled diabetes/ hypertension or infections can affect it
how can maternal nutrition affect development
dietary insufficiencies can produce defects
how can maternal stress affect development
physical stress can cause low birth weight and congenital malformations
how can placental toxicity affect development
smoke, arsenic, and alcohols can affect placental attachment, nutrition, and gas exchange
how can maternal toxicity affect development
can cause intrauterine death, low birth weight, abnormal rib or pelvic formations
what can alterations to the placenta result in
altered:
metabolism
distribution
uptake
elimination processes
how does the placenta influence embryonic exposure to toxins
regulation of blood flow
acts as a transport barrier
metabolizes chemicals
acts as a lipid membrane for bidirectional transfer of substances
factors that affect the transfer of substances from placenta to fetus include
lipid solubility and blood flow
molecular weight
protein binding
type of diffusion/transport
ionization
metabolism
critical periods of developmental toxicity susceptibility
gametogenesis/fertilization
pre-implantation of zygote
gastrulation
organogenesis
fetal period
what developmental toxicities occur during gametogenesis/fertilization
the early stages of genome formation and stabilization can result in changes of DNA methylation resulting in dysfunction of stability and chromatin confirmation affecting stability and structure
what developmental toxicities occur during pre-implantatoin
before the zygote implants on the wall of the uterus; toxicities can cause death of zygote and if death does not occur no anomalies are developed due to period of rapid cell growth
what developmental toxicities occur during gastrulation
period of formation of the three germ layers can result in eye, brain, and face malformations
what developmental toxicities occur during organogenesis
occurs from weeks 3-8 in gestation, toxicities in arise in whatever bodily structures are being formed
what developmental toxicities occur during the fetal period
all organs are developed and are maturing, toxicities result in anomalies of the CNS (cognitive behavior and motor deficits) and of reproductive organs and decreased fertility
criteria used for classifying agents as teratogens
agent produces adverse developmental effects
all 4 manifestations are of concern for developing: death, structural abnormalities, growth alterations, and functional abnormalities
if applicable there is a known dose-response toxicity that results in develo
examples of developmental toxicities
thalidomide
diethylstilbestrol
ethanol
tobacco smoke
cocaine
retinoids
anti-epileptics
ACE inhibitors
Describe fetal toxicities associated with tobacco smoke
toxicity occurs through smoke or second hand smoke resulting in miscarriage, sudden infant death syndrome and altered physiological function of lungs
Describe fetal toxicities associated with cocaine
acts as a local anesthetic and vasoconstrictor resulting in placental ruptures, premature labor/delivery, and CNS issues
Describe fetal toxicities associated with retinoids
occurs with high vitamin A exposure and results in miscarriage and mental retardation
Describe fetal toxicities associated with anti-epileptic drugs
prevent seizures and result in fetal brain defects, cognitive impairment and fetal death
Describe fetal toxicities associated with ACE inhibitors
cause bone issues and malformations and lower amniotic fluid volume resulting in renal failure and death
Describe fetal toxicities associated with thalidomide
used as a sleep aid to improve systems of nausea and vomiting; resulting in newborns missing limbs or reduction of long bones, malformation of eyes, intestines and kidneys
Describe fetal toxicities associated with diethylstilbestrol (DES)
used as a miscarriage preventative, synthetic nonsteroidal estrogen resulting in vaginal clear adenocarcinoma
Describe fetal toxicities associated with ethanol
fetal alcohol syndrome causing growth retardation and craniofacial malformations
refers to cellular-level events that initiate the process leading to abnormal development
mechanisms
list examples of mechanistic events of toxicity
genetic mutations
chromosome breaks
altered mitosis
altered nucleic acid function
what do mechanistic events of developmental toxicity result in
altered cell-cell interactions
differentiation
morphogenesis
energy metabolism
comprises the cell, tissue and organ-level sequelae that ultimately manifest in abnormality
pathogenesis
factors that play a role in biological thresholds that toxicity in embryo depend on
maternal metabolic defenses
cell homeostasis mechanisms
restorative growth potential
what are the two thresholds that toxicity in the embryo is based on and what are the adverse effects that can happen as well as the factors that play a role
two thresholds: mother and fetus, both have biological thresholds that are dependent on repair and defense systems being able to combat exposure separately
adverse effects include: post-implantation pregnancy loss, neurological deficits, low birth weight,
theory that suggests that developmental environment influences metabolic parameters of offspring that persist throughout their lives and may result in increased risk of developing diseases
developmental programming
theory that links maternal nutrition to the deterioration of offspring organs and body postnatal
fetal programming