SlideShare ist ein Scribd-Unternehmen logo
1 von 144
Downloaden Sie, um offline zu lesen
Johari M. Ancheta, MD, DPSP
Davao Medical School Foundation
1ST PART
• Environmental Effects on Global Disease Burden
• Health Effects of Climate Change
• Toxicity of Chemical and Physical Agents
• Environmental Pollution
• Occupational Health Risks
Environmental Diseases
• Many human diseases are caused or
influenced by environmental factors
• Environment = indoor, outdoor, and
occupational settings in w/c human beings
live and work
• Things which we are exposed to or consume
are major determinants of health in this
setting
• Individual personal behavior > ambient
environment
Environmental Diseases
• Refers to conditions caused by exposure to
chemical or physical agents in the ambient,
workplace, and personal environment,
including diseases of nutritional origin
• Examples:
Dramatic
• Dioxin exposure in Italy
• Methyl isocyanate gas leak
in Bhopal, India
• Fukushima nuclear
meltdown
Subtle
• Work related exposure or
accidents
• Nutritional deficiencies:50%
of childhood mortality
worldwide
Environmental Effects on
Global Disease Burden
On a worldwide basis:
• dramatic increases in mortality due to HIV/AIDS and
assoc. infxns
Undernutrition
• single leading global cause of health loss (defined as
morbidity and premature death)
Ischemic heart disease and CVD
• remain the leading causes of death in developed countries
In developing countries
• 5 of the 10 leading causes of death are infectious dses
Environmental Effects on
Global Disease Burden
• In the postnatal period, about 50% of all
deaths in children younger than 5 years
of age are attributed to only three
conditions, all preventable:
Pneumonia
Diarrheal diseases
Malaria
Environmental and nutritional diseases animated
Environmental Effects on
Global Disease Burden
Emerging infectious diseases
• Infectious disorders whose incidence has recently
increased or could reasonably be expected to increase in
the near future
• Change in envt’l and socioeconomic conditions
• Categories:
Diseases caused by
newly evolved strains or
organisms
Diseases caused by
pathogens endemic in
other species that
“jumped” to human
population
Diseases caused by
pathogens that have
been present in humans
but show a recent
increase in incidence
Health Effects of Climate
Change
Measurements show that earth has warmed at an
accelerating rate over the past 50 yrs
Since 1960, the global ave. temp. has increased by
≈ 0.6°C, with the greatest increases seen over land
areas bet. 40 degrees north and 70 degrees north
9 of the 10 hottest years in the meteorologic record
have occurred in the 21st century
Health Effects of Climate
Change
• glaciers may disappear by the year 2025
• arctic ocean will be completely ice-free in
summer by the year 2040
Rapid loss of
glacial and sea ice
leading to
predictions that:
• particularly carbon dioxide (CO2) released
through the burning of fossil fuels
• as well as ozone (an important air
pollutant, discussed later) and methane
Principal culprit is
the rising
atmospheric level
of greenhouse
gases
Health Effects of Climate
Change
• Greenhouse effect = absorption and re-emission
of infrared energy radiated from the earth’s
surface that otherwise would be lost into space
• Atmospheric CO2 in late 2012 (about 391 ppm)
was higher than at any point in ≈ 650,000 yrs
• Expected to increase to between 500 to
1200 ppm by the end of this century
• Increased CO2 production but also from
deforestation and the attendant decrease in
carbon fixation by plants
Health Effects of Climate
Change
• also projected to increase the variability
and severity of weather events, such as
floods, droughts, and storms
Increased heat
energy in the oceans
and atmosphere
• is increasing acidity of the oceans, which
may disrupt marine ecosystems and
fisheries
Increased
atmospheric
CO2 conc.
• will raise sea levels by at least 1 to 2 feet
by 2100
Combined w/
thermal expansion
of warming oceans
Health Effects of Climate
Change
• Its Extent and rapidity
• Nature and severity of ensuing consequences
• Humankind’s ability to mitigate the damage
Health impacts of
climate change will
depend on:
• Cardiovascular, cerebrovascular,
and respiratory dses
• Gastroenteritis, cholera, and other
foodborne and waterborne infectious dses
• Vector-borne infectious dses
(ex: malaria, dengue)
• Malnutrition
Climate change is
expected to have
serious impact on
health by increasing
incidence of dses
Health Effects of Climate
Change
• The resulting displacement of people will disrupt
lives and commerce, creating conditions ripe for
political unrest, war, and poverty, the “vectors” of
malnutrition, sickness, and death
• Both developed and developing countries will
suffer the consequences of climate change
• Burden will be greatest in developing countries
• The urgent challenge is to develop new
renewable energy resources that stem the
production of greenhouse gases
Toxicity of Chemical & Physical
Agents
• Distribution
• Effects
• Mechanisms of action of toxic agents
• Effects of physical agents such as radiation
and heat
Toxicology =
the science of poisons
Only a very small proportion has been tested experimentally for
health effects
• Interaction between various pollutants, and
the age, genetic predisposition ≈ tissue
sensitivities of exposed persons
• Variations in individual sensitivity to toxic
agents
Factors
Toxicity of Chemical & Physical
Agents
• basically a quantitative concept strictly
dependent on dosagePoisons
“All substances are poisons; the right dosage differentiates a poison from
a remedy”
– Paracelsus
• exogenous chemicals in the environment in air,
water, food, and soil that may be absorbed
into the body through inhalation, ingestion,
and skin contact
Xenobiotics
Xenobiotics
Toxicity of Chemical & Physical
Agents
Chemicals may
be
• excreted in urine
or feces
• eliminated in
expired air
• or may
accumulate in
bone, fat, brain,
or other tissues
Chemicals may
act
• at the site of
entry
• or at other sites
following
transport
through the
blood
Most solvents
and drugs are
lipophilic
• which facilitates
their transport in
the blood by
lipoproteins and
their penetration
through the
plasma
membrane into
cells
Most solvents,
drugs, and
xenobiotics are
• metabolized to
form inactive
water-soluble
products
(detoxification)
• activated to form
toxic metabolites
Toxicity of Chemical & Physical
Agents• Reactions that metabolize xenobiotics occur in 2 phases
• Form water-soluble compounds that are readily
excreted
• Drug-metabolizing enzymes = enzymes that catalyze
the biotransformation of xenobiotics and drugs
Phase I reactions
• chemicals undergo
hydrolysis, oxidation or
reduction
Phase II reactions
• include
glucuronidation,
sulfation, methylation,
and conjugation with
glutathione
Environmental and nutritional diseases animated
Toxicity of Chemical & Physical
Agents
• The cytochrome P-450 (CYP) system
catalyzes reactions that either
– detoxify xenobiotics
– or, less commonly, convert
xenobiotics into active compounds
that cause cellular injury
• Both types of reactions may produce,
as a byproduct, reactive oxygen
species (ROS), which can cause cellular
damage
Toxicity of Chemical & Physical
Agents
• Great variation in the activity of CYPs among
individuals
• Variation may be a consequence of genetic
polymorphisms in specific CYPs
• More commonly it is due to exposure to drugs
or chemicals that induce or diminish CYP
activity
CYP inducers:
environmental
chemicals, drugs,
smoking, alcohol, and
hormones
Fasting or starvation
can decrease CYP
activity
Toxicity of Chemical & Physical
Agents
• Inducers of CYP = binding to nuclear receptors, which then
heterodimerize with the retinoic X receptor (RXR)
• Form a transcriptional activation complex that associates
with promoter elements located in the 5′-flanking region of
CYP genes
• Nuclear receptors forCYP induction:
Aryl hydrocarbon
receptor
Peroxisome
proliferator-
activated
receptors (PPAR)
Nuclear receptors:
androstane receptor
(CAR), and pregnane
X receptor (PXR)
Environmental Pollution
• Air pollution
– Air is vital to life, but also contains many causes of disease
– Significant cause of morbidity and mortality worldwide,
particularly among at-risk individuals with preexisting
pulmonary or cardiac disease
Outdoor air pollution
• Ambient air in industrialized nations is contaminated
with mixture of gaseous and particulate pollutants
Indoor air pollution
• “Buttoned up” homes to exclude the environment
Environmental Pollution
• Outdoor Air Pollution
• “Smog” – concoction of six pollutants
• Affect mainly the lungs although other organ
systems are also affected
Sulfur dioxide
Carbon
monoxide
Ozone
Nitrogen
dioxide
Lead
Particulate
matter
Pollutant Populations at Risk Effects
Ozone
Healthy adults and children
Decreased lung function
Increased airway reactivity
Lung inflammation
Athletes, outdoor workers
Asthmatics
Decreased exercise capacity
Increased hospitalizations
Nitrogen dioxide
Healthy adults Increased airway reactivity
Asthmatics Decreased lung function
Children Increased respiratory infections
Sulfur dioxide
Healthy adults Increased respiratory symptoms
Individuals with chronic lung disease Increased mortality
Asthmatics
Increased hospitalization
Decreased lung function
Acid aerosols
Healthy adults Altered mucociliary clearance
Children Increased respiratory infections
Asthmatics
Decreased lung function
Increased hospitalizations
Particulates
Children Increased respiratory infections
Individuals with chronic lung or heart
disease
Decreased lung function
Asthmatics
Excess mortality
Increased attacks
Environmental Pollution
• Good ozone (Stratospheric O3)
– Produced by interaction of ultraviolet (UV)
radiation and oxygen (O2) in the stratosphere
– Protects life on earth by absorbing the most
dangerous UV radiation emitted by the sun
– Ozone layer decreased in both thickness and
extent due to the widespread use of
chlorofluorocarbon gases in air conditioners and
refrigerators and as aerosol propellants
Environmental Pollution
• Bad ozone (Ground-level O3)
– Formed by the reaction of nitrogen oxides and
volatile organic compounds in the presence of
sunlight
– Toxicity due to production of free radicals, which
injure epithelial cells along the respiratory tract &
type I alveolar cells
– Cause the release of inflammatory mediators
• Sulfur dioxide
– Produced by power plants burning coal and oil, from
copper smelting, and as a byproduct of paper mills
– Converted into sulfuric acid and sulfuric trioxide
Environmental Pollution
• Particulate matter (known as “soot”)
– Particulates are emitted by coal- and oil-fired power plants, by
industrial processes
– Fine or ultrafine particles less than 10 µm in diameter are the
most harmful
• Carbon monoxide
– Systemic asphyxiant that is an important cause of accidental
and suicidal death
– Nonirritating, colorless, tasteless, odorless gas that is produced
during any process that results in the incomplete oxidation of
hydrocarbons
– CO kills in part by inducing central nervous system (CNS)
depression, which appears so insidiously that victims are often
unaware of their plight
– Hemoglobin has 200-fold greater affinity for CO than for
oxygen
Environmental Pollution
Chronic CO poisoning
• Ischemic changes in the basal ganglia
and lenticular nuclei
• Residual permanent neurologic
sequelae
Acute CO poisoning
• Characteristic generalized cherry-red
color of the skin and mucous
membranes
• High levels of carboxyhemoglobin
Environmental Pollution
• Indoor air pollution
– Wood smoke
• Oxides of nitrogen and carbon particulates,
• Irritant that may predispose to lung infections
• Contain polycyclic hydrocarbons, important carcinogens
– Bioaerosols
• Microbiologic agents capable of causing infectious
diseases
• Pet dander, dust mites, and fungi and molds responsible
for rhinitis, eye irritation, and asthma.
Environmental Pollution
• Indoor air pollution
– Radon
• Radioactive gas derived from uranium widely present in soil
and in homes
• Cause lung cancer in uranium miners
– Formaldehyde
• Building materials (e.g., cabinetry, furniture, adhesives)
• Breathing difficulties and a burning sensation in the eyes
and throat
• Carcinogen for humans and animals
– Sick building syndrome
• May be a consequence of exposure to one or more indoor
pollutants, possibly due to poor ventilation
Environmental Pollutions:
METALS
Lead
Readily absorbed metal that binds to sulfhydryl groups in proteins
Interferes with calcium metabolism
Lead to hematologic, skeletal, neurologic, gastrointestinal, and renal
toxicities
House paints and gasoline
Low-level lead poisoning include subtle deficits in intellectual capacity,
behavioral problems such as hyperactivity, and poor organizational skills
Environmental and nutritional diseases animated
Environmental and nutritional diseases animated
Mercury
• Mercury binds to sulfhydryl groups in certain proteins with
high affinity, leading to damage in the CNS and the kidney
• 3 forms of mercury
• Main sources of exposure
Metallic mercury
• also known as
elemental mercury
Inorganic mercury
• mostly mercuric
chloride
Organic mercury
• mostly methyl
mercury
Contaminated fish (methyl mercury)
Mercury vapors released from metallic mercury in
dental amalgams & mercury used in gold mining
Mercury
• The developing brain is extremely sensitive to methyl
mercury
• Lipid solubility of methyl mercury and metallic mercury
facilitate their accumulation in the brain, disturbing
neuromotor, cognitive, and behavioral fxns
• There are serious concerns about the effects of chronic
low-level exposure to methyl mercury in food
exposure of the fetus
to high levels of
mercury in utero
Minamata disease
(cerebral palsy,
deafness, and
blindness)
Arsenic
• Interfere with several aspects of cellular metabolism,
leading to toxicities most prominent in GI tract,
nervous system, skin, and heart
• Sources:
– Naturally occurring in soils and water & is used in
products such as wood preservers, herbicides and
other agricultural products
– Mines and smelting industries
– Chinese and Indian herbal medicine
• Large concentrations of inorganic arsenic are
present in ground water in countries such as
Bangladesh, Chile, and China
“The poison of kings and the king of
poisons”
Arsenic
Most toxic forms of arsenic are the trivalent compounds:
arsenic trioxide, sodium arsenite, and arsenic trichloride
Causes acute GI, cardiovascular, and CNS toxicities that are often fatal
Interference with mitochondrial oxidative phosphorylation
Also has pleiotropic effects on the activity of a number of other enzymes
and ion channels, and these too may contribute to certain toxicities
Arsenic
• Usually occur 2 to 8 weeks after exposure
• Paresthesias, numbness, and pain
Neurologic effects
• Hyperpigmentation and hyperkeratosisSkin changes
• The most serious consequence of chronic
exposure
• Particularly of the lungs, bladder and skin
• Arsenic-induced skin tumors - often multiple
and usually appear on the palms and soles
Increased risk for
the development
of cancers
• Chronic exposure to arsenic in drinking water
Non-malignant
respiratory disease
Cadmium
• Preferentially toxic to kidneys and lungs through
increased production of reactive oxygen species
• Sources:
Pollutant generated by mining, electroplating,
and production of nickel-cadmium batteries
Can contaminate the soil and plants directly or
through fertilizers and irrigation water
Food is the most important source of cadmium
exposure for the general population
Cadmium
• Principal toxic effects of excess cadmium
• caused by necrosis of alveolar epithelial cells
Obstructive lung
disease
• may progress to end-stage renal disease
Renal tubular
damage
• associated with calcium loss
Skeletal
abnormalities
• combination of osteoporosis and osteomalacia
• associated with renal disease
“Itai-itai”
• associated with an elevated risk of lung cancerLung cancer
Occupational
Health Risks
Occupational Health Risks
• Consequence of work-related accidents
and illnesses
• Work-related accidents are the biggest
occupational health problem in developing
countries
• Work-related diseases are more frequent
in industrialized countries
Environmental and nutritional diseases animated
Occupational Health Risks
• Organic solvents
– Chloroform and carbon tetrachloride found in degreasing and dry
cleaning agents and paint removers
– Cause dizziness and confusion, leading to CNS depression and
even coma
– Lower levels are toxic for the liver and kidneys
– Exposure of rubber workers to benzene and 1,3-
butadiene increases the risk of leukemia
• Polycyclic hydrocarbons
– Released during the combustion of fossil fuels, particularly
when coal and gas are burned at high temperatures
– In tar and soot
– Among the most potent carcinogens, and industrial exposures
have been implicated in the dev’t of lung and bladder cancer
Occupational Health Risks
• Organochlorines
– Synthetic lipophilic products that resist degradation
– Pesticides include DDT
(dichlorodiphenyltrichloroethane), lindane, aldrin,
and dieldrin
– Nonpesticide organochlorines
include polychlorinated biphenyls (pcbs)
and dioxin (tcdd; 2,3,7,8-tetrachlorodibenzo-p-
dioxin)
– Organochlorines disrupt hormonal balance because
of antiestrogenic or antiandrogenic activity
– Dioxins and pcbs - folliculitis and chloracne (acne,
cyst formation, hyperpigmentation, and
hyperkeratosis)
Occupational Health Risks
• Mineral dusts
– Chronic, non-neoplastic lung disease = PNEUMOCONIOSIS
– Exposures to coal dust (e.G., Mining of hard coal), silica (e.G.,
Sandblasting, stone cutting), asbestos (e.G., Mining,
fabrication, insulation work), and beryllium (e.G, mining,
fabrication)
• Vinyl chloride
– Synthesis of polyvinyl resins leads to the development of
angiosarcoma of the liver
• Bisphenol A
– Synthesis of polycarbonate food and water containers and of
epoxy resins that line almost all food bottles and cans
– Long been known as a potential endocrine disruptor
TOBACCO
Effects of Tobacco
Most readily preventable cause of death in humans
Cigarette smoking, “snuff”, “2nd hand smoke”
30% of all smokers worldwide live in China,
10% live in India
Cause 90% of lung cancers
Tobacco contains between 2000 and 4000 substances, more
than 60 of which have been identified as carcinogens
Environmental and nutritional diseases animated
Environmental and nutritional diseases animated
Smoking and Lung Cancer
• Direct irritant effect on the tracheobronchial
mucosa
• Inflammation and increased mucus
production (bronchitis)
• Causes the recruitment of leukocytes to the
lung, with increased local elastase production
and subsequent injury to lung tissue, leading
to emphysema
• Polycyclic hydrocarbons and nitrosamines
• Risk of developing lung cancer is related to
the number of pack years or cigarettes
smoked per day
Environmental and nutritional diseases animated
Smoking is linked to
many other malignant
and nonmalignant
disorders that affect
numerous organ
systems
Maternal smoking
increases risk of
abortion,
premature birth,
and intrauterine
growth retardation
ALCOHOL
Effects of Alcohol
• Excessive amounts alcohol causes serious
physical and psychological damage
• Alcohol abuse is a far more widespread
hazard and claims many more lives
–Drunken driving and alcohol-related
homicides and suicides
–Consequence of cirrhosis of the liver
Alcohol Concentration in the Blood
• 80 mg/dl = legal definition of drunk driving
– After 3 standard drinks, about three (12 ounce)
bottles of beer, 15 ounces of wine, or 4 to 5
ounces of 80 proof distilled spirits
• 200 mg/dl = drowsiness occurs
• 300 mg/dl = stupor
• Higher levels = coma with possible respiratory arrest
• Rate of metabolism affects blood alcohol level
• Chronic alcoholics can tolerate levels of up to
700 mg/dl due to accelerated ethanol metabolism
Metabolism of Alcohol
• Absorbed unaltered
• Metabolized by 3 enzyme
systems:
– CYP2E1
– Alcohol Dehydrogenase
(ADH)
– Catalase
• Acetaldehyde – acted upon
by Aldehyde
Dehydrogenase to form
Acetic acid
Metabolites of Alcohol
• Acetaldehyde
– Responsible for some of the acute effects of alcohol and for
the development of oral cancers
– ALDH2*2 gene = low ALDH activity
• Cannot tolerate alcohol, experiencing nausea, flushing,
tachycardia, and hyperventilation
• NADH/NAD
– Increased NADH & decreased NAD = fatty liver & lactic
acidosis
• ROS
– Produced by CYP2E1
– Lipid peroxidation of plasma membrane
– Causes release of endotoxin from enteric bacteria =
TNF & other cytokines resulting to hepatic damage
Adverse Effects of Alcohol
Acute alcoholism
• Mainly on the CNS, but it may induce hepatic and
gastric changes that are reversible if alcohol
consumption is discontinued
• Fatty change or hepatic steatosis
• Acute gastritis and ulceration
• Disordered cortical, motor, intellectual behavior &
depressed, including those that regulate
respiration. Respiratory arrest
Adverse Effects of Alcohol
Chronic alcoholism
• Significant morbidity and have a shortened life span, related
principally to damage to the liver, gastrointestinal tract, CNS,
cardiovascular system, and pancreas
• Cirrhosis
• Thiamine (vitamin B1) deficiency = peripheral neuropathies &
Wernicke-Korsakoff Syndrome
• Alcoholic cardiomyopathy
• Acute and chronic pancreatitis
• Fetal alcohol syndrome
• Increased incidence of cancer of the oral cavity, esophagus, liver
Moderate consumption of
Alcohol
• 20-30 gm/day, corresponding to
approximately 250 ml of wine
• ↑ high-density lipoprotein (HDL) levels
• Inhibit platelet aggregation
• ↓ fibrinogen levels
• Light to moderate alcohol consumption =
↑ overall survival as compared to
teetotalers and heavy drinkers
END OF 1ST PART
2ND PART
• Injury byTherapeutic Drugs and
Drugs of Abuse
• Injury by Physical Agents
• Nutritional Diseases
INJURY BY THERAPEUTIC DRUGS
AND DRUGS OF ABUSE
Injury by Therapeutic Drugs
(Adverse Drug Reactions)
• Adverse drug reactions = untoward effects of
drugs that are given in conventional
therapeutic settings
• Due to direct actions of the drug or to
immunologically based hypersensitivity
reactions
Example of Adverse Drug
Reaction
Environmental and nutritional diseases animated
Anticoagulants
• Warfarin (Vitamin K antagonist) and
Dabigatran (direct thrombin inhibitor)
Menopausal Hormone Therapy
• Previously known as HRT (hormone replacement therapy)
• Administration of estrogens together with a progestogen
• Counteract symptoms of menopause, could prevent or
slow the progression of osteoporosis and reduce the
likelihood of myocardial infarction
Increased the risk of breast cancer, stroke, and
venous thromboembolism and had no effect
on the incidence of coronary heart disease
Should not be used long term for chronic
disease prevention
Oral Contraceptives
• OCs nearly always contain a synthetic estradiol and a
variable amount of a progestin, but some preparations
contain only progestins
• Inhibiting ovulation or preventing implantation
Increased risk of cervical cancer in HPV infected women
Threefold to sixfold increased risk of venous thrombosis and
pulmonary thromboembolism
Increase in cardiovascular diseases in women (>35 yo) who
smoke
Hepatic adenoma in older women with prolonged use
Anabolic Steroids
Synthetic versions of testosterone
Inhibits production and release of luteinizing hormone & follicle-
stimulating hormone by a feedback mechanism
Increases the amount of estrogens
Stunted growth in adolescents, acne, gynecomastia, and testicular atrophy
in males, and growth of facial hair and menstrual changes in women
Psychiatric disturbances
Increased risk of myocardial infarction. Hepatic cholestasis
Acetaminophen
• Most commonly used analgesic, toxicity is common
• Detoxification in the liver by phase II enzymes
• Is excreted in the urine as glucuronate or sulfate
conjugates
95% of
acetaminophen
undergoes
detoxification
• NAPQI (n-acetyl-p-benzoquinoneimine) is a
highly reactive metabolite
• When acetaminophen is taken in large doses,
unconjugated NAPQI accumulates and causes
hepatocellular injury
5% or less is
metabolized
through CYPs
(primarily CYP2E)
to NAPQI
Acetaminophen
• 50% of cases of acute liver failure, with 30% mortality
• NAPQI mechanism of injury:
• Nausea, vomiting, diarrhea, and sometimes shock,
followed in a few days by evidence of jaundice
• Centrilobular necrosis that may progress to liver failure
1. Covalent binding to
hepatic proteins, which
causes damage to cellular
membranes and
mitochondrial dysfunction
2. Depletion of GSH,
making hepatocytes more
susceptible to reactive
oxygen species-induced
injury
Environmental and nutritional diseases animated
Aspirin: Acetylsalicylic acid
• Acute salicylate overdose causes alkalosis
as a consequence of the stimulation of the
respiratory center in the medulla
• Followed by metabolic acidosis and
accumulation of pyruvate and lactate,
caused by uncoupling of oxidative
phosphorylation and inhibition of the
Krebs cycle
• Nausea to coma
Aspirin
• Chronic aspirin toxicity (Salicylism)
– Headaches, dizziness, ringing in the ears
(tinnitus), hearing impairment, mental
confusion, drowsiness, nausea, vomiting,
and diarrhea
– Acute erosive gastritis, gastric ulceration,
gastric bleeding
– Bleeding tendency
– Analgesic nephropathy = tubulointerstitial
nephritis with renal papillary necrosis
INJURY BY
NONTHERAPEUTIC
AGENTS
(DRUG ABUSE)
Injury by Nontherapeutic Agents
(Drug Abuse)
• Illicit substance
• Occasional users of illicit “recreational”
drugs suffer no apparent long-term health
effects
• Acute effects may take a significant toll in
the form of accidents, violence, or even fatal
drug-related complications
• Generally involves the repeated or chronic
use of mind-altering substances, beyond
therapeutic or social norms, and may lead
to drug addiction and overdose, both
serious public health problems
Environmental and nutritional diseases animated
Cocaine
• Extracted from the leaves of the coca plant, and is
usually prepared as a water-soluble powder,
cocaine hydrochloride
• Can be snorted or dissolved in water and injected
subcutaneously or intravenously
• “Crack” form is far more potent
• Intense euphoria and stimulation, making it one
of the most addictive drugs
– Physical dependence generally does not occur
– Psychologic withdrawal is profound
& extremely difficult to treat
Cocaine
• Acute and chronic effects
– Tachycardia, hypertension, and peripheral
vasoconstriction, may also induce myocardial
ischemia
– Precipitate lethal arrhythmias
– Hyperpyrexia (thought to be caused by
aberrations of the dopaminergic pathways
that control body temperature) and seizures
– Acute decreases in blood flow to the placenta,
resulting in fetal hypoxia and spontaneous
abortion
– Perforation of the nasal septum in snorters
– Decreased lung diffusing capacity in
those who inhale the smoke
– Dilated cardiomyopathy
Opiates
• Opiate drugs of abuse include synthetic
prescription opiates such as oxycodone
(oxycontin) and “street drugs,” most
notably heroin
• An addictive opioid derived from the
poppy plant that is closely related to
morphine
• Even more harmful than that of cocaine
• Effects on the CNS are varied and
include euphoria, hallucinations,
somnolence, and sedation
Heroin
• Adverse effects
• Profound respiratory depression, arrhythmia and cardiac
arrest, and severe pulmonary edemaSudden death
• Severe edema, septic embolism, granulomasPulmonary injury
• S. Aureus, but fungi and a multitude of other organisms
have also been implicatedInfections
• Abscesses, cellulitis, and ulcerations due to subcutaneous
injections, hyperpigmentation over commonly used veinsSkin
• Amyloidosis, focal and segmental glomerulosclerosis;
both induce proteinuria and the nephrotic syndromeKidneys
Amphetamines and Related
Drugs
Methamphetamine
• “speed” or “meth”
• stronger effects in the CNS
• inhibits presynaptic
neurotransmission at
corticostriatal synapses,
slowing glutamate release
• Long-term use leads to violent
behaviors, confusion, and
psychotic features that include
paranoia and hallucinations
MDMA
• 3,4 methylenedioxymethamphetamine =
“Ecstasy”
• taken orally
• effects, which include euphoria and
hallucinogen-like feelings that last 4 to 6
hours
• partly attributable to an increase in
serotonin release in the CNS
• reduces the number of serotonergic axon
terminals in the striatum and the cortex,
and it may increase the peripheral
effects of dopamine and adrenergic
agents
Marijuana
• Most widely used illicit drug globally
• “Pot”, “weed”
• Leaves of the cannabis sativa plant,
which contain the psychoactive
substance δ9-tetrahydrocannabinol
(THC)
• Untoward anecdotal effects allergic or
idiosyncratic reactions or possibly
related to contaminants in the
preparations rather than to the
pharmacologic effects of marijuana
Marijuana
• Beneficial effects of marijuana
– treat nausea secondary to cancer chemotherapy
and as an agent capable of decreasing pain in
some chronic conditions
• Distorts sensory perception and impairs motor
coordination
– acute effects clear in 4 to 5 hours
• With continued use cognitive and psychomotor
impairments occur a potential cause of
automobile accidents
• Increases the heart rate and blood pressure,
and it may cause angina in a person with
coronary artery disease
Marijuana
• Chronic marijuana smoking
– laryngitis, pharyngitis, bronchitis, cough
and hoarseness, and asthma-like
symptoms have all been described,
along with mild but significant airway
obstruction
• Large number of carcinogens that are also
present in tobacco
• Smoking a marijuana cigarette, compared
with a tobacco cigarette, is associated w/
threefold increase in amount of tar inhaled
Other Drugs
PCP (phencyclidine, an
anesthetic agent) = “OOBE”
Vicodin, and ketamine, an
anesthetic agent
Spray paints, paint thinners,
and some glues that contain
TOLUENE
• Mild to severe dementia
• Bizarre and often aggressive behavior
that leads to violence or depressed
mood and suicidal ideation
“Bath salts”
• Contain 4-methyl-meth-cathinone and
methylenedioxypyrovalerone
• Amphetamine-like effects when
snorted or eaten
• Agitation, psychosis, myocardial
infarction, and suicide
INJURY BY PHYSICAL AGENTS
Mechanical trauma
• Type of injury depends on the shape of the
colliding object, the amount of energy
discharged at impact, and the tissues or
organs that bear the impact
• Mechanical forces, and the patterns of
injury can be divided into abrasions,
contusions, lacerations, incised wounds,
and puncture wounds
• Forensic pathology
Thermal Injury
• Excessive heat and excessive cold are
important causes of injury
– Thermal burns
– Hyperthermia
– Hypothermia
Thermal Burns
• Caused by fire or by scalding
• Consequence of injuries caused by fire and smoke inhalation
• Clinical significance of a burn injury:
Depth of the burns
Percentage of body surface involved
Internal injuries caused by the inhalation of hot and toxic fumes
Promptness and efficacy of therapy, especially fluid and electrolyte
management and prevention or control of wound infections
Thermal Burns
• According to the depth of the injury
Superficial burns
• Formerly known as
first-degree burns
• Confined to the
epidermis
Partial thickness burns
• Formerly known as
second-degree
burns
• Involve injury to the
dermis
Full-thickness burns
• Formerly known as
third-degree burns:
extend to the
subcutaneous tissue
• Formerly known as
fourth-degree burns:
involve damage to
muscle tissue
underneath the
subcutaneous tissue
Thermal Burns
• Greatest threats to life
Shock,
sepsis, and respiratory
insufficiency
• Systemic inflammatory response syndrome = shock
• Hypermetabolic state = increased need for
nutritional support
Burns of more than 20% of
the body surface
• Pseudomonas aeruginosa
• Methicillin-resistant S. Aureus
• Candida species
Infection
• Early excision and grafting of the burn wound
Organ system failure
resulting from burn sepsis
• Inhalation of heated air and noxious gases in the
smoke
Injury to the airways and
lungs
Hyperthermia
• Prolonged exposure to elevated ambient
temperatures
• Heat cramps
– Loss of electrolytes via sweating
– Cramping of voluntary muscles, in association with
vigorous exercise, is the hallmark
– Heat-dissipating mechanisms are able to maintain
normal core body temperature
• Heat exhaustion
– Most common: hyperthermic syndrome
– Prostration and collapse, and it results from a failure
of the cardiovascular system to compensate for
hypovolemia caused by dehydration
– After a period of collapse, which is usually brief,
equilibrium is spontaneously re-established if the
victim is able to rehydrate
Hyperthermia
• Heat stroke
– Associated with high ambient temperatures,
high humidity, and exertion
– Thermoregulatory mechanisms fail, sweating
ceases, and the core body temperature rises
to more than 40°C, leading to multiorgan
dysfunction that can be rapidly fatal
– Generalized vasodilation, with peripheral
pooling of blood and a decreased effective
circulating blood volume
– Hyperkalemia, tachycardia, arrhythmias, and
other systemic effects
Hyperthermia
• Malignant hyperthermia
– Characterized by a “heat-stroke–like” rise in core
body temperature and muscle contractures
following exposure to common anesthetics due to
inherited mutations in RYR1
– Ryanodine receptor 1 (RYR1), which is located in
the sarcoplasmic reticulum of skeletal muscle
• RYR1 regulates the release of calcium from the
sarcoplasm
• Heat stroke deranges RYR1 function →calcium
to leak into the cytoplasm→muscle contraction
and heat production
Hypothermia
• Prolonged exposure to low ambient
temperature
• High humidity, wet clothing, and dilation
of superficial blood vessels resulting from
the ingestion of alcohol hasten the
lowering of body temperature
• Body temperature of about 90°F (32.2°C):
loss of consciousness occurs, followed by
bradycardia and atrial fibrillation at lower
core temperatures
Hypothermia
• Hypothermic injury:
• Slow chilling may induce vasoconstriction and
increase vascular permeability, leading to edema
and hypoxia = “trench foot”
• Sudden, persistent chilling, the vasoconstriction and
increased viscosity of the blood in the local area
may cause ischemic injury and degenerative
changes in peripheral nerves
Direct effects
• Mediated by physical disruptions
within cells by high salt
concentrations caused by the
crystallization of intra- and
extracellular water
Indirect effects
• Circulatory changes, which vary
depending on the rate and duration
of the temperature drop
Electrical Injury
• Contact with low-voltage currents (i.e., at home
and workplace) or high-voltage currents carried
by high-power lines or produced by lightning
• Two types of injuries:
1. Burns
2. Ventricular fibrillation OR cardiac &
respiratory center failure
• Depend on the strength (amperage), duration,
and path of the electric current within the
body
Electrical Injury
• Voltage in the household and workplace (120 or 220 V)
is high enough that with low resistance at the site of
contact , sufficient current can pass through the body
to cause serious injury, including ventricular fibrillation
• Alternating current (AC)
– Type supplied to most homes
– Induces tetanic muscle spasm, so that when a live
wire or switch is grasped, irreversible clutching is
likely to occur, prolonging the period of current flow
– Extensive electrical burns and spasm of the chest
wall muscles, producing death from asphyxia
Electrical Injury
Currents generated from high-voltage sources
• Cause similar damage
The large current flows generated are more likely to
produce paralysis of medullary centers and extensive burns
• Lightning
Magnetic fields and microwave radiation
• Produce burns, usually of the skin and subjacent
connective tissue when sufficiently intense
Ionizing Radiation Injury
• Energy that travels in the form of waves or high-speed
particlesRadiation
• Ex: UV and infrared light, microwave, and sound waves
• Can move atoms in a molecule or cause them to vibrate,
but is not sufficient to displace bound electrons from
atoms
Nonionizing
Radiation
• Has sufficient energy to remove tightly bound electrons
• X-rays and gamma rays, high-energy neutrons, alpha
particles and beta particles
Ionizing
Radiation
• Fibrosis, mutagenesis, carcinogenesis, and teratogenesisCauses:
Ionizing Radiation Injury
• Units of radiation
Curie (Ci)
an expression of
the amount of
radiation
emitted by a
source
Gray (Gy)
is a unit that
expresses the
energy
absorbed by the
target tissue per
unit mass
Sievert (Sv)
is a unit of
equivalent dose
that depends on
the biologic
rather than the
physical effects
of radiation
Ionizing Radiation Injury
• Biologic effects of Radiation determinants
• Cumulative effect = fractioned dosesRate of delivery
• Body area of exposure = higher doses tolerated if
limited area is exposedField size
• rapidly dividing cells are more vulnerable to injury
than are quiescent cellsCell proliferation
• production of reactive oxygen species
Oxygen effects and
hypoxia
• Damage to endothelial cells = narrowing or
occlusion of blood vesselsVascular damage
Environmental and nutritional diseases animated
Environmental and nutritional diseases animated
Environmental and nutritional diseases animated
Ionizing Radiation Injury
NUTRITIONAL DISEASES
Malnutrition
• Consequence of inadequate intake of
proteins and calories, or deficiencies in
the digestion or absorption of proteins
• Loss of fat and muscle tissue, weight
loss, lethargy, and generalized weakness
• Developing nations
– malnutrition, starvation, obesity
Dietary insufficiency
• Appropriate diet:
• Primary malnutrition – one or all of these
components are missing from the diet
• Secondary malnutrition – malnutrition results from
malabsorption, impaired utilization or storage, excess
loss, or increased need for nutrients
sufficient energy
amino acids and fatty acids
• to be used as building blocks
for synthesis of proteins and
lipids
vitamins and minerals
• function as coenzymes or
hormones in vital metabolic
pathways
• or, as in the case of calcium
and phosphate, as important
structural components
Conditions that lead to malnutrition
Poverty Infections
Acute and
chronic illnesses
Chronic
alcoholism
Ignorance and
failure of diet
supplementation
Self-imposed
dietary
restriction
Other causes
Protein Energy Malnutrition
(PEM)• Determined by body mass index
– Weight in kilograms divided by height in meters squared
– Normal range 18.5 to 25 kg/m2
• Thickness of skin folds – fat stores
• Circumference of mid-arm – muscle mass
• Serum proteins – visceral protein
• 2 spectrums of PEM syndromes:
Marasmus
• somatic compartment,
represented by proteins in
skeletal muscles
Kwashiorkor
• visceral compartment,
represented by protein stores in
the visceral organs, primarily
the liver
Marasmus
• Weight falls to 60% of normal for
sex, height, and age
• Growth retardation and loss of
muscle
• Visceral protein compartment
minimally depleted
• Serum albumin levels are either
normal or only slightly reduced
• Extremities are emaciated
• Anemia & immune deficiency
Kwashiorkor
• Protein deprivation is relatively more
severe than the deficit in total calories
• Severe depletion of the visceral
protein compartment
• Hypoalbuminemia =
generalized or dependent edema
• Skin lesions = flaky paint
• Hair changes = flag sign
• Fatty liver, apathy, listlessness, and
loss of appetite
• Defects in immunity and secondary
infections
Cachexia
• PEM in AIDS or advanced cancers
• Extreme weight loss, fatigue, muscle atrophy,
anemia, anorexia, and edema
• Mediators secreted by tumors and during
chronic inflammatory reactions
Proteolysis-
inducing factor
• glycosylated
polypeptide
Lipid-mobilizing
factor
• TNF and IL-6
Environmental and nutritional diseases animated
Anorexia Nervosa and Bulimia
Anorexia nervosa
• Highest death rate of any
psychiatric disorder
• Altered serotonin metabolism
• Similar to those in severe PEM
• Amenorrhea
• Decreased thyroid hormone
release
• Bone density is decreased
• Cardiac arrhythmia & sudden
death
Bulimia
• Large amounts of food,
principally carbohydrates, are
ingested, only to be followed by
induced vomiting
• Menstrual irregularities
• Frequent vomiting and the
chronic use of laxatives and
diuretics
• Electrolyte imbalances
• Pulmonary aspiration
• Esophageal and gastric
rupture
• Cardiac arrhythmia & sudden
death
Vitamin Deficiencies
• Thirteen vitamins are necessary for health
– Fat soluble and water soluble
• Vitamins A, D, E, and K are fat-soluble
• Fat-soluble vitamins are more readily stored
in the body
• Endogenous synthesis of vitamins: D, K &
niacin
• Deficiencies:
– Primary = dietary insufficiency
– Secondary = disturbances in absorption,
transport, storage or metabolism
Vitamin A
• Retinol (alcohol), retinal
(aldehyde), and retinoic acid (acid)
• Fat soluble
• Functions:
Maintenance
of normal
vision
Cell growth
and
differentiation
Host
resistance to
infections
Adipogenesis
and fatty acid
metabolism
Vitamin A
Deficiency
• Occurs due to:
undernutrition or
malabsorption of fats
• Night blindness
• Epithelial metaplasia and
keratinization
– Xerophthalmia
– Bitot’s spots
– Keratomalacia
– Squamous metaplasia
Toxicity
• Liver = polar bear,
whales, sharks and tuna
• Acute
– Headache, dizziness,
vomiting, stupor, and
blurred vision,
pseudotumor cerebri
• Increased osteoclast
activity
• Teratogenic effect of
retinoids
Vitamin D
• Endogenously synthesized
fat soluble vitamin; deep-sea
fish, plants, and grains are
dietary sources
• Cholecalciferol (vitamin D3)
• Maintenance plasma levels
of calcium and phosphorus
– Metabolic functions
– Bone mineralization
– Neuromuscular
transmission
Functions:
Stimulation of intestinal
calcium absorption
Stimulation of calcium
reabsorption in the kidney
Interaction with PTH in the
regulation of blood calcium
Mineralization of bone –
osteocalcin
Vitamin D
Deficiency – insufficient diet
and limited sun exposure
– Rickets
• Craniotabes
• Frontal bossing
• Rachitic rosary
• Pigeon breast deformity
• Bowing of the legs
– Osteomalacia
• Gross fractures or
microfractures
– Hypocalcemic tetany
– Osteoporosis (vitamin D
insufficiency)
Vit D supplements –
increased lymphocyte count,
enhanced clearance of MTB
in sputum
Toxicity
– Megadoses of oral vitamins
– Not from prolonged
exposure to sunlight
– Metastatic calcifications
– Bone pain
– Hypercalcemia
Vitamin C
• Water soluble vitamin
• Ascorbic acid
• Entirely dependent on
the diet for this nutrient
• Milk and some animal
products (liver, fish) and
is abundant in a variety
of fruits and vegetables
• Functions:
Activation of prolyl and lysyl
hydroxylases
Hydroxylation of procollagen
Promotes secretion of
procollagen
Antioxidant properties – direct
and indirect
Vitamin C
• Vitamin excess
– Mild antihistamine action =Tx for common colds
– Toxicities are rare
• Iron overload due to increased absorption
• Hemolytic anemia in G6PD deficiency patients
• Calcium oxalate stones
Trace Elements
Obesity
• An accumulation of adipose tissue that is of
sufficient magnitude to impair health
• ↑ Incidence type 2 diabetes, dyslipidemias,
cardiovascular disease, hypertension, and cancer
• BMI measurements
18.5 to 25 kg/m2
Normal BMI
range
25 to 30 kg/m2Overweight
> 30 kg/m2Obese
Obesity
• Distribution of the stored fat
– Central, or visceral, obesity
– Subcutaneous obesity
• Refined sugars, sweetened beverages, and
vegetable oils
• Disease of caloric imbalance
– Intake of calories ≥ calorie consumption
– Genetic influences play an important role
in weight control
– But the interaction between multiple
factors
Obesity
• Neurohumoral control of energy balance
– Peripheral or afferent system – generates signals
Leptin PeptideYY
Adiponectin Insulin
Ghrelin
– Arcuate nucleus in hypothalamus - processes and
integrates neurohumoral signals
• POMC (pro-opiomelanocortin) and CART (cocaine and
amphetamine-regulated transcripts) neurons
• NPY (neuropeptideY) and AgRP (Agouti-Related Peptide)
neurons
– Efferent system
• Anabolic – control food intake
• Catabolic – control energy expenditure
Environmental and nutritional diseases animated
Environmental and nutritional diseases animated
Components of the Afferent System
• Regulates appetite and satiety
• Leptin
– Product of the ob gene
– 16-kd hormone synthesized by fat cells
– Signal for energy sufficiency = leptin secretion is stimulated when
fat stores are abundant
– Stimulates POMC/CART neurons that produce anorexigenic
neuropeptides
– Stimulates physical activity, heat production, and energy
expenditure
• Adiponectin (guardian angel against obesity)
– Hormone is produced mainly by adipocytes
– Directs fatty acids to muscle for their oxidation
– Decreases the influx of fatty acids to the liver &
decreases glucose production
– Increase in insulin sensitivity
– Inactivates acetyl coa carboxylase
thru binding with adipor1 and R2
Components of the Afferent System
• Gut hormones
• Ghrelin
– Produced in the stomach and arcuate nucleus of the
hypothalamus
– The only known gut hormone that is orexigenic effect
– Likely to stimulate NPY/AgRP neurons
– Post-prandial level attenuation = overeating
• PYY
– Secreted by endocrine cells in the ileum & colon
– Reduces energy intake
– Stimulates POMC/CART neurons
• Amylin
– Peptide secreted with insulin by β cells
– Reduces food intake and weight gain
– Stimulates POMC/CART neurons
Consequences of Obesity
Consequences of Obesity
• Metabolic syndrome
– Visceral adiposity, insulin resistance, hyperinsulinemia, glucose
intolerance, hypertension, hypertriglyceridemia, and low HDL
cholesterol
• Insulin resistance and hyperinsulinemia
• ↑ Risk coronary artery disease
• Nonalcoholic fatty liver disease
• Cholelithiasis (gallstones)
• Hypoventilation syndrome (Pickwickian syndrome)
– Hypersomnolence
– Sleep apnea
– Cor pulmonale
• Osteoarthritis
Obesity and Cancer
• ↑ risk for cancers of the esophagus, pancreas,
colon and rectum, breast, endometrium,
kidney, thyroid, and gallbladder
• Possibly due to the following:
Elevated
insulin levels
Effects on
steroid
hormone
Low
adiponectin
levels
= Elevated
insulin
Pro-
inflammatory
state
Diet and Cancer
• Incidence of cancer varies
with geographic areas
• Environmental factors
clearly play a role including
diet
• There are few mechanisms
that link diets and specific
types of cancer
• Aspects of diet concerned
with Carcinogenesis
– Content of exogenous
carcinogens
– Endogenous synthesis of
carcinogens from dietary
components
– Lack of protective factors
• Exogenous carcinogens
– Aflatoxin = liver CA
– Food additives, pesticides,
artificial sweeteners
• Endogenous carcinogens
– Gastric CA
– Nitrosamines
– Nitrosamides
• High animal fat and low
fiber
– Colon CA
– Breast CA
• Low vitamins
– Vitamin C, β carotene,
selenium,Vitamin D
Diet and Atherosclerosis
• Association of dietary cholesterol and
saturated animal fats with development of
atherosclerosis
• Role that caloric restriction and special
diets may play in the control of body
weight and prevention of cardiovascular
disease
• Activation of sirtuins and on lowering of
insulin and IGF-1 levels
Diet and Atherosclerosis
• Focus on eating an enjoyable and
healthy diet
Rich in fish Vegetables Whole grains Fruits
Olive and
peanut oils
Complex
carbohydrates
Low salt
END

Weitere ähnliche Inhalte

Was ist angesagt?

Vibration Disease caused by Physical agents
Vibration Disease caused by Physical agentsVibration Disease caused by Physical agents
Vibration Disease caused by Physical agentsEneutron
 
Neoplasia Etiology and pathogenesis of cancer
Neoplasia Etiology and pathogenesis of cancerNeoplasia Etiology and pathogenesis of cancer
Neoplasia Etiology and pathogenesis of cancerSubramani Parasuraman
 
Disorders of minerals metabolism
Disorders of minerals metabolismDisorders of minerals metabolism
Disorders of minerals metabolismAbdul Wahab
 
Occupational and environmental causes of lung cancer
Occupational and environmental causes of lung cancerOccupational and environmental causes of lung cancer
Occupational and environmental causes of lung cancerBikash Singh
 
Silicosis
SilicosisSilicosis
SilicosisShahdYr
 
Cell injury : Intracellular accumulations
Cell injury : Intracellular accumulationsCell injury : Intracellular accumulations
Cell injury : Intracellular accumulationsVijay Shankar
 
Hyperemia and congestion edema
Hyperemia and congestion edema Hyperemia and congestion edema
Hyperemia and congestion edema pathologydept
 
Fa1zanS: Disorder of exchange of Chromoprotein (endogenous pigment). Disorder...
Fa1zanS: Disorder of exchange of Chromoprotein (endogenous pigment). Disorder...Fa1zanS: Disorder of exchange of Chromoprotein (endogenous pigment). Disorder...
Fa1zanS: Disorder of exchange of Chromoprotein (endogenous pigment). Disorder...Faizan Siddiqui
 
Respiratory diseases
Respiratory diseasesRespiratory diseases
Respiratory diseasesBhawna Rajput
 
Difference between reversible and irreversible cell injury,Mechanism of cell ...
Difference between reversible and irreversible cell injury,Mechanism of cell ...Difference between reversible and irreversible cell injury,Mechanism of cell ...
Difference between reversible and irreversible cell injury,Mechanism of cell ...Rukhshanda Ramzaan
 
Chronic Renal Failure (UG)
Chronic Renal Failure (UG)Chronic Renal Failure (UG)
Chronic Renal Failure (UG)Dr Ashutosh Ojha
 
Hygiene of soil
Hygiene of soilHygiene of soil
Hygiene of soilAlok Kumar
 
Asbestos&Berylliosis
Asbestos&BerylliosisAsbestos&Berylliosis
Asbestos&BerylliosisPrasad CSBR
 
Disorders of Renal Function by Dr Kemi Dele
Disorders of Renal Function by Dr Kemi DeleDisorders of Renal Function by Dr Kemi Dele
Disorders of Renal Function by Dr Kemi DeleKemi Dele-Ijagbulu
 

Was ist angesagt? (20)

Vibration Disease caused by Physical agents
Vibration Disease caused by Physical agentsVibration Disease caused by Physical agents
Vibration Disease caused by Physical agents
 
Neoplasia Etiology and pathogenesis of cancer
Neoplasia Etiology and pathogenesis of cancerNeoplasia Etiology and pathogenesis of cancer
Neoplasia Etiology and pathogenesis of cancer
 
Disorders of minerals metabolism
Disorders of minerals metabolismDisorders of minerals metabolism
Disorders of minerals metabolism
 
Occupational and environmental causes of lung cancer
Occupational and environmental causes of lung cancerOccupational and environmental causes of lung cancer
Occupational and environmental causes of lung cancer
 
Silicosis
SilicosisSilicosis
Silicosis
 
Cell injury : Intracellular accumulations
Cell injury : Intracellular accumulationsCell injury : Intracellular accumulations
Cell injury : Intracellular accumulations
 
Part i head and neck pathology
Part i  head and neck pathologyPart i  head and neck pathology
Part i head and neck pathology
 
Hyperemia and congestion edema
Hyperemia and congestion edema Hyperemia and congestion edema
Hyperemia and congestion edema
 
Fa1zanS: Disorder of exchange of Chromoprotein (endogenous pigment). Disorder...
Fa1zanS: Disorder of exchange of Chromoprotein (endogenous pigment). Disorder...Fa1zanS: Disorder of exchange of Chromoprotein (endogenous pigment). Disorder...
Fa1zanS: Disorder of exchange of Chromoprotein (endogenous pigment). Disorder...
 
Respiratory diseases
Respiratory diseasesRespiratory diseases
Respiratory diseases
 
Difference between reversible and irreversible cell injury,Mechanism of cell ...
Difference between reversible and irreversible cell injury,Mechanism of cell ...Difference between reversible and irreversible cell injury,Mechanism of cell ...
Difference between reversible and irreversible cell injury,Mechanism of cell ...
 
Neoplasia
NeoplasiaNeoplasia
Neoplasia
 
Chronic Renal Failure (UG)
Chronic Renal Failure (UG)Chronic Renal Failure (UG)
Chronic Renal Failure (UG)
 
7 shock
7 shock7 shock
7 shock
 
Blood disorders ppt
Blood disorders pptBlood disorders ppt
Blood disorders ppt
 
Hygiene of soil
Hygiene of soilHygiene of soil
Hygiene of soil
 
Haematological diseases
Haematological diseasesHaematological diseases
Haematological diseases
 
Asbestos&Berylliosis
Asbestos&BerylliosisAsbestos&Berylliosis
Asbestos&Berylliosis
 
Intracellular accumulations
Intracellular accumulations Intracellular accumulations
Intracellular accumulations
 
Disorders of Renal Function by Dr Kemi Dele
Disorders of Renal Function by Dr Kemi DeleDisorders of Renal Function by Dr Kemi Dele
Disorders of Renal Function by Dr Kemi Dele
 

Andere mochten auch

Environmental+sanitation
Environmental+sanitationEnvironmental+sanitation
Environmental+sanitationpramod kumar
 
Environmental diseases
Environmental diseasesEnvironmental diseases
Environmental diseasesNunkoo Raj
 
Environmental Diseases
Environmental DiseasesEnvironmental Diseases
Environmental DiseasesKarly Rose
 
Respiratory Diseases
Respiratory DiseasesRespiratory Diseases
Respiratory Diseasesshas595
 
Hygiene & Sanitation Presentation for Hotel & Restaurants by Ravi
Hygiene & Sanitation Presentation for Hotel & Restaurants  by RaviHygiene & Sanitation Presentation for Hotel & Restaurants  by Ravi
Hygiene & Sanitation Presentation for Hotel & Restaurants by RaviHM Rav
 
K TO 12 GRADE 7 LEARNING MODULE IN ARTS
K TO 12 GRADE 7 LEARNING MODULE IN ARTSK TO 12 GRADE 7 LEARNING MODULE IN ARTS
K TO 12 GRADE 7 LEARNING MODULE IN ARTSLiGhT ArOhL
 
K TO 12 GRADE 7 LEARNING MODULE IN HEALTH (Q3-Q4)
K TO 12 GRADE 7 LEARNING MODULE IN HEALTH (Q3-Q4)K TO 12 GRADE 7 LEARNING MODULE IN HEALTH (Q3-Q4)
K TO 12 GRADE 7 LEARNING MODULE IN HEALTH (Q3-Q4)LiGhT ArOhL
 
Disease health grade 7 third quarter
Disease health grade 7 third quarterDisease health grade 7 third quarter
Disease health grade 7 third quarterElmer Llames
 

Andere mochten auch (10)

Environmental+sanitation
Environmental+sanitationEnvironmental+sanitation
Environmental+sanitation
 
SANITATION
SANITATIONSANITATION
SANITATION
 
Environmental diseases
Environmental diseasesEnvironmental diseases
Environmental diseases
 
Environmental Diseases
Environmental DiseasesEnvironmental Diseases
Environmental Diseases
 
Respiratory Diseases
Respiratory DiseasesRespiratory Diseases
Respiratory Diseases
 
Hygiene & Sanitation Presentation for Hotel & Restaurants by Ravi
Hygiene & Sanitation Presentation for Hotel & Restaurants  by RaviHygiene & Sanitation Presentation for Hotel & Restaurants  by Ravi
Hygiene & Sanitation Presentation for Hotel & Restaurants by Ravi
 
Health and environment
Health and environmentHealth and environment
Health and environment
 
K TO 12 GRADE 7 LEARNING MODULE IN ARTS
K TO 12 GRADE 7 LEARNING MODULE IN ARTSK TO 12 GRADE 7 LEARNING MODULE IN ARTS
K TO 12 GRADE 7 LEARNING MODULE IN ARTS
 
K TO 12 GRADE 7 LEARNING MODULE IN HEALTH (Q3-Q4)
K TO 12 GRADE 7 LEARNING MODULE IN HEALTH (Q3-Q4)K TO 12 GRADE 7 LEARNING MODULE IN HEALTH (Q3-Q4)
K TO 12 GRADE 7 LEARNING MODULE IN HEALTH (Q3-Q4)
 
Disease health grade 7 third quarter
Disease health grade 7 third quarterDisease health grade 7 third quarter
Disease health grade 7 third quarter
 

Ähnlich wie Environmental and nutritional diseases animated

Contemporary issues and social engineering Module 1.pptx
Contemporary issues and social engineering Module 1.pptxContemporary issues and social engineering Module 1.pptx
Contemporary issues and social engineering Module 1.pptxaiswaryavvg
 
Impact of Human Activities
Impact of Human ActivitiesImpact of Human Activities
Impact of Human ActivitiesNoah Ark Angel
 
Dr Amit Purushottam (Climate Change and Ethics)
Dr Amit Purushottam (Climate Change and Ethics)Dr Amit Purushottam (Climate Change and Ethics)
Dr Amit Purushottam (Climate Change and Ethics)DrAmitPurushottam
 
Health impacts of environmental pollution
Health impacts of environmental pollutionHealth impacts of environmental pollution
Health impacts of environmental pollutionPECB
 
Environmental and nutritional diseases
Environmental and nutritional diseasesEnvironmental and nutritional diseases
Environmental and nutritional diseasesMaria Alonieh Sepe
 
03 pollutants harm effects
03 pollutants harm effects03 pollutants harm effects
03 pollutants harm effectsfathi neana
 
Effect of climate change on human health.pptx
Effect of climate change on human health.pptxEffect of climate change on human health.pptx
Effect of climate change on human health.pptxPradeep Pande
 
Basic concept of environmental pollution
Basic concept of environmental pollutionBasic concept of environmental pollution
Basic concept of environmental pollutionBipin Karki
 
06 pollutants harm effects
06  pollutants harm effects06  pollutants harm effects
06 pollutants harm effectsfathi neana
 
B sc micro, biotech, biochem i es u 3.1 ecosystem
B sc micro, biotech, biochem i es u 3.1 ecosystemB sc micro, biotech, biochem i es u 3.1 ecosystem
B sc micro, biotech, biochem i es u 3.1 ecosystemRai University
 
10Green House Effect & Global Warming.pdf
10Green House Effect & Global Warming.pdf10Green House Effect & Global Warming.pdf
10Green House Effect & Global Warming.pdfShubhamParmar75
 
04 pollutants harm effects
04  pollutants harm effects04  pollutants harm effects
04 pollutants harm effectsfathi neana
 
Effects of Climate Change on Chemicals
Effects of Climate Change on ChemicalsEffects of Climate Change on Chemicals
Effects of Climate Change on ChemicalsAyse Özcan
 
Chapter 4 (Climate Change and Human Health).pptx
Chapter 4 (Climate Change and Human Health).pptxChapter 4 (Climate Change and Human Health).pptx
Chapter 4 (Climate Change and Human Health).pptxhuseinmuzayen
 
insecticide pollution, persistance and problems associated with agriculture
insecticide pollution, persistance and problems associated with agricultureinsecticide pollution, persistance and problems associated with agriculture
insecticide pollution, persistance and problems associated with agricultureSafeena Majeed
 
Environmental Pollution & Health Issues
Environmental Pollution & Health Issues Environmental Pollution & Health Issues
Environmental Pollution & Health Issues Atosa Morshedi
 

Ähnlich wie Environmental and nutritional diseases animated (20)

Contemporary issues and social engineering Module 1.pptx
Contemporary issues and social engineering Module 1.pptxContemporary issues and social engineering Module 1.pptx
Contemporary issues and social engineering Module 1.pptx
 
Impact of Human Activities
Impact of Human ActivitiesImpact of Human Activities
Impact of Human Activities
 
Dr Amit Purushottam (Climate Change and Ethics)
Dr Amit Purushottam (Climate Change and Ethics)Dr Amit Purushottam (Climate Change and Ethics)
Dr Amit Purushottam (Climate Change and Ethics)
 
Health impacts of environmental pollution
Health impacts of environmental pollutionHealth impacts of environmental pollution
Health impacts of environmental pollution
 
Environmental and nutritional diseases
Environmental and nutritional diseasesEnvironmental and nutritional diseases
Environmental and nutritional diseases
 
03 pollutants harm effects
03 pollutants harm effects03 pollutants harm effects
03 pollutants harm effects
 
Effect of climate change on human health.pptx
Effect of climate change on human health.pptxEffect of climate change on human health.pptx
Effect of climate change on human health.pptx
 
Industrial pollution
Industrial pollutionIndustrial pollution
Industrial pollution
 
Basic concept of environmental pollution
Basic concept of environmental pollutionBasic concept of environmental pollution
Basic concept of environmental pollution
 
06 pollutants harm effects
06  pollutants harm effects06  pollutants harm effects
06 pollutants harm effects
 
Global environmental changes
Global environmental changesGlobal environmental changes
Global environmental changes
 
AIR POLLUTION.pptx
AIR POLLUTION.pptxAIR POLLUTION.pptx
AIR POLLUTION.pptx
 
B sc micro, biotech, biochem i es u 3.1 ecosystem
B sc micro, biotech, biochem i es u 3.1 ecosystemB sc micro, biotech, biochem i es u 3.1 ecosystem
B sc micro, biotech, biochem i es u 3.1 ecosystem
 
10Green House Effect & Global Warming.pdf
10Green House Effect & Global Warming.pdf10Green House Effect & Global Warming.pdf
10Green House Effect & Global Warming.pdf
 
505 chapte 4.pptx
505 chapte 4.pptx505 chapte 4.pptx
505 chapte 4.pptx
 
04 pollutants harm effects
04  pollutants harm effects04  pollutants harm effects
04 pollutants harm effects
 
Effects of Climate Change on Chemicals
Effects of Climate Change on ChemicalsEffects of Climate Change on Chemicals
Effects of Climate Change on Chemicals
 
Chapter 4 (Climate Change and Human Health).pptx
Chapter 4 (Climate Change and Human Health).pptxChapter 4 (Climate Change and Human Health).pptx
Chapter 4 (Climate Change and Human Health).pptx
 
insecticide pollution, persistance and problems associated with agriculture
insecticide pollution, persistance and problems associated with agricultureinsecticide pollution, persistance and problems associated with agriculture
insecticide pollution, persistance and problems associated with agriculture
 
Environmental Pollution & Health Issues
Environmental Pollution & Health Issues Environmental Pollution & Health Issues
Environmental Pollution & Health Issues
 

Kürzlich hochgeladen

Mental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil ThirusanguMental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil Thirusangu Medical University
 
Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024Peter Embi
 
Unit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptUnit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptPradnya Wadekar
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .Mohamed Rizk Khodair
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project reportNARMADAPETROLEUMGAS
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets barmohitRahangdale
 
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptxANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptxWINCY THIRUMURUGAN
 
BENIGN BREAST DISEASE
BENIGN BREAST DISEASE BENIGN BREAST DISEASE
BENIGN BREAST DISEASE Mamatha Lakka
 
Using Data Visualization in Public Health Communications
Using Data Visualization in Public Health CommunicationsUsing Data Visualization in Public Health Communications
Using Data Visualization in Public Health Communicationskatiequigley33
 
How to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyHow to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyZurück zum Ursprung
 
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxDNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxMAsifAhmad
 
CPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentCPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentsaileshpanda05
 
Male Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondMale Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondSujoy Dasgupta
 
historyofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusanguhistoryofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusangu Medical University
 
pA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacologypA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacologyDeepakDaniel9
 
Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Vaikunthan Rajaratnam
 

Kürzlich hochgeladen (20)

Mental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil ThirusanguMental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil Thirusangu
 
Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024
 
Unit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptUnit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.ppt
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project report
 
GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets bar
 
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptxANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
 
BENIGN BREAST DISEASE
BENIGN BREAST DISEASE BENIGN BREAST DISEASE
BENIGN BREAST DISEASE
 
How to master Steroid (glucocorticoids) prescription, different scenarios, ca...
How to master Steroid (glucocorticoids) prescription, different scenarios, ca...How to master Steroid (glucocorticoids) prescription, different scenarios, ca...
How to master Steroid (glucocorticoids) prescription, different scenarios, ca...
 
Using Data Visualization in Public Health Communications
Using Data Visualization in Public Health CommunicationsUsing Data Visualization in Public Health Communications
Using Data Visualization in Public Health Communications
 
American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...
 
How to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyHow to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturally
 
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxDNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
 
Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...
 
CPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentCPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing student
 
Male Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondMale Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and Beyond
 
historyofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusanguhistoryofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusangu
 
pA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacologypA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacology
 
Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.
 

Environmental and nutritional diseases animated

  • 1. Johari M. Ancheta, MD, DPSP Davao Medical School Foundation
  • 2. 1ST PART • Environmental Effects on Global Disease Burden • Health Effects of Climate Change • Toxicity of Chemical and Physical Agents • Environmental Pollution • Occupational Health Risks
  • 3. Environmental Diseases • Many human diseases are caused or influenced by environmental factors • Environment = indoor, outdoor, and occupational settings in w/c human beings live and work • Things which we are exposed to or consume are major determinants of health in this setting • Individual personal behavior > ambient environment
  • 4. Environmental Diseases • Refers to conditions caused by exposure to chemical or physical agents in the ambient, workplace, and personal environment, including diseases of nutritional origin • Examples: Dramatic • Dioxin exposure in Italy • Methyl isocyanate gas leak in Bhopal, India • Fukushima nuclear meltdown Subtle • Work related exposure or accidents • Nutritional deficiencies:50% of childhood mortality worldwide
  • 5. Environmental Effects on Global Disease Burden On a worldwide basis: • dramatic increases in mortality due to HIV/AIDS and assoc. infxns Undernutrition • single leading global cause of health loss (defined as morbidity and premature death) Ischemic heart disease and CVD • remain the leading causes of death in developed countries In developing countries • 5 of the 10 leading causes of death are infectious dses
  • 6. Environmental Effects on Global Disease Burden • In the postnatal period, about 50% of all deaths in children younger than 5 years of age are attributed to only three conditions, all preventable: Pneumonia Diarrheal diseases Malaria
  • 8. Environmental Effects on Global Disease Burden Emerging infectious diseases • Infectious disorders whose incidence has recently increased or could reasonably be expected to increase in the near future • Change in envt’l and socioeconomic conditions • Categories: Diseases caused by newly evolved strains or organisms Diseases caused by pathogens endemic in other species that “jumped” to human population Diseases caused by pathogens that have been present in humans but show a recent increase in incidence
  • 9. Health Effects of Climate Change Measurements show that earth has warmed at an accelerating rate over the past 50 yrs Since 1960, the global ave. temp. has increased by ≈ 0.6°C, with the greatest increases seen over land areas bet. 40 degrees north and 70 degrees north 9 of the 10 hottest years in the meteorologic record have occurred in the 21st century
  • 10. Health Effects of Climate Change • glaciers may disappear by the year 2025 • arctic ocean will be completely ice-free in summer by the year 2040 Rapid loss of glacial and sea ice leading to predictions that: • particularly carbon dioxide (CO2) released through the burning of fossil fuels • as well as ozone (an important air pollutant, discussed later) and methane Principal culprit is the rising atmospheric level of greenhouse gases
  • 11. Health Effects of Climate Change • Greenhouse effect = absorption and re-emission of infrared energy radiated from the earth’s surface that otherwise would be lost into space • Atmospheric CO2 in late 2012 (about 391 ppm) was higher than at any point in ≈ 650,000 yrs • Expected to increase to between 500 to 1200 ppm by the end of this century • Increased CO2 production but also from deforestation and the attendant decrease in carbon fixation by plants
  • 12. Health Effects of Climate Change • also projected to increase the variability and severity of weather events, such as floods, droughts, and storms Increased heat energy in the oceans and atmosphere • is increasing acidity of the oceans, which may disrupt marine ecosystems and fisheries Increased atmospheric CO2 conc. • will raise sea levels by at least 1 to 2 feet by 2100 Combined w/ thermal expansion of warming oceans
  • 13. Health Effects of Climate Change • Its Extent and rapidity • Nature and severity of ensuing consequences • Humankind’s ability to mitigate the damage Health impacts of climate change will depend on: • Cardiovascular, cerebrovascular, and respiratory dses • Gastroenteritis, cholera, and other foodborne and waterborne infectious dses • Vector-borne infectious dses (ex: malaria, dengue) • Malnutrition Climate change is expected to have serious impact on health by increasing incidence of dses
  • 14. Health Effects of Climate Change • The resulting displacement of people will disrupt lives and commerce, creating conditions ripe for political unrest, war, and poverty, the “vectors” of malnutrition, sickness, and death • Both developed and developing countries will suffer the consequences of climate change • Burden will be greatest in developing countries • The urgent challenge is to develop new renewable energy resources that stem the production of greenhouse gases
  • 15. Toxicity of Chemical & Physical Agents • Distribution • Effects • Mechanisms of action of toxic agents • Effects of physical agents such as radiation and heat Toxicology = the science of poisons Only a very small proportion has been tested experimentally for health effects • Interaction between various pollutants, and the age, genetic predisposition ≈ tissue sensitivities of exposed persons • Variations in individual sensitivity to toxic agents Factors
  • 16. Toxicity of Chemical & Physical Agents • basically a quantitative concept strictly dependent on dosagePoisons “All substances are poisons; the right dosage differentiates a poison from a remedy” – Paracelsus • exogenous chemicals in the environment in air, water, food, and soil that may be absorbed into the body through inhalation, ingestion, and skin contact Xenobiotics
  • 18. Toxicity of Chemical & Physical Agents Chemicals may be • excreted in urine or feces • eliminated in expired air • or may accumulate in bone, fat, brain, or other tissues Chemicals may act • at the site of entry • or at other sites following transport through the blood Most solvents and drugs are lipophilic • which facilitates their transport in the blood by lipoproteins and their penetration through the plasma membrane into cells Most solvents, drugs, and xenobiotics are • metabolized to form inactive water-soluble products (detoxification) • activated to form toxic metabolites
  • 19. Toxicity of Chemical & Physical Agents• Reactions that metabolize xenobiotics occur in 2 phases • Form water-soluble compounds that are readily excreted • Drug-metabolizing enzymes = enzymes that catalyze the biotransformation of xenobiotics and drugs Phase I reactions • chemicals undergo hydrolysis, oxidation or reduction Phase II reactions • include glucuronidation, sulfation, methylation, and conjugation with glutathione
  • 21. Toxicity of Chemical & Physical Agents • The cytochrome P-450 (CYP) system catalyzes reactions that either – detoxify xenobiotics – or, less commonly, convert xenobiotics into active compounds that cause cellular injury • Both types of reactions may produce, as a byproduct, reactive oxygen species (ROS), which can cause cellular damage
  • 22. Toxicity of Chemical & Physical Agents • Great variation in the activity of CYPs among individuals • Variation may be a consequence of genetic polymorphisms in specific CYPs • More commonly it is due to exposure to drugs or chemicals that induce or diminish CYP activity CYP inducers: environmental chemicals, drugs, smoking, alcohol, and hormones Fasting or starvation can decrease CYP activity
  • 23. Toxicity of Chemical & Physical Agents • Inducers of CYP = binding to nuclear receptors, which then heterodimerize with the retinoic X receptor (RXR) • Form a transcriptional activation complex that associates with promoter elements located in the 5′-flanking region of CYP genes • Nuclear receptors forCYP induction: Aryl hydrocarbon receptor Peroxisome proliferator- activated receptors (PPAR) Nuclear receptors: androstane receptor (CAR), and pregnane X receptor (PXR)
  • 24. Environmental Pollution • Air pollution – Air is vital to life, but also contains many causes of disease – Significant cause of morbidity and mortality worldwide, particularly among at-risk individuals with preexisting pulmonary or cardiac disease Outdoor air pollution • Ambient air in industrialized nations is contaminated with mixture of gaseous and particulate pollutants Indoor air pollution • “Buttoned up” homes to exclude the environment
  • 25. Environmental Pollution • Outdoor Air Pollution • “Smog” – concoction of six pollutants • Affect mainly the lungs although other organ systems are also affected Sulfur dioxide Carbon monoxide Ozone Nitrogen dioxide Lead Particulate matter
  • 26. Pollutant Populations at Risk Effects Ozone Healthy adults and children Decreased lung function Increased airway reactivity Lung inflammation Athletes, outdoor workers Asthmatics Decreased exercise capacity Increased hospitalizations Nitrogen dioxide Healthy adults Increased airway reactivity Asthmatics Decreased lung function Children Increased respiratory infections Sulfur dioxide Healthy adults Increased respiratory symptoms Individuals with chronic lung disease Increased mortality Asthmatics Increased hospitalization Decreased lung function Acid aerosols Healthy adults Altered mucociliary clearance Children Increased respiratory infections Asthmatics Decreased lung function Increased hospitalizations Particulates Children Increased respiratory infections Individuals with chronic lung or heart disease Decreased lung function Asthmatics Excess mortality Increased attacks
  • 27. Environmental Pollution • Good ozone (Stratospheric O3) – Produced by interaction of ultraviolet (UV) radiation and oxygen (O2) in the stratosphere – Protects life on earth by absorbing the most dangerous UV radiation emitted by the sun – Ozone layer decreased in both thickness and extent due to the widespread use of chlorofluorocarbon gases in air conditioners and refrigerators and as aerosol propellants
  • 28. Environmental Pollution • Bad ozone (Ground-level O3) – Formed by the reaction of nitrogen oxides and volatile organic compounds in the presence of sunlight – Toxicity due to production of free radicals, which injure epithelial cells along the respiratory tract & type I alveolar cells – Cause the release of inflammatory mediators • Sulfur dioxide – Produced by power plants burning coal and oil, from copper smelting, and as a byproduct of paper mills – Converted into sulfuric acid and sulfuric trioxide
  • 29. Environmental Pollution • Particulate matter (known as “soot”) – Particulates are emitted by coal- and oil-fired power plants, by industrial processes – Fine or ultrafine particles less than 10 µm in diameter are the most harmful • Carbon monoxide – Systemic asphyxiant that is an important cause of accidental and suicidal death – Nonirritating, colorless, tasteless, odorless gas that is produced during any process that results in the incomplete oxidation of hydrocarbons – CO kills in part by inducing central nervous system (CNS) depression, which appears so insidiously that victims are often unaware of their plight – Hemoglobin has 200-fold greater affinity for CO than for oxygen
  • 30. Environmental Pollution Chronic CO poisoning • Ischemic changes in the basal ganglia and lenticular nuclei • Residual permanent neurologic sequelae Acute CO poisoning • Characteristic generalized cherry-red color of the skin and mucous membranes • High levels of carboxyhemoglobin
  • 31. Environmental Pollution • Indoor air pollution – Wood smoke • Oxides of nitrogen and carbon particulates, • Irritant that may predispose to lung infections • Contain polycyclic hydrocarbons, important carcinogens – Bioaerosols • Microbiologic agents capable of causing infectious diseases • Pet dander, dust mites, and fungi and molds responsible for rhinitis, eye irritation, and asthma.
  • 32. Environmental Pollution • Indoor air pollution – Radon • Radioactive gas derived from uranium widely present in soil and in homes • Cause lung cancer in uranium miners – Formaldehyde • Building materials (e.g., cabinetry, furniture, adhesives) • Breathing difficulties and a burning sensation in the eyes and throat • Carcinogen for humans and animals – Sick building syndrome • May be a consequence of exposure to one or more indoor pollutants, possibly due to poor ventilation
  • 34. Lead Readily absorbed metal that binds to sulfhydryl groups in proteins Interferes with calcium metabolism Lead to hematologic, skeletal, neurologic, gastrointestinal, and renal toxicities House paints and gasoline Low-level lead poisoning include subtle deficits in intellectual capacity, behavioral problems such as hyperactivity, and poor organizational skills
  • 37. Mercury • Mercury binds to sulfhydryl groups in certain proteins with high affinity, leading to damage in the CNS and the kidney • 3 forms of mercury • Main sources of exposure Metallic mercury • also known as elemental mercury Inorganic mercury • mostly mercuric chloride Organic mercury • mostly methyl mercury Contaminated fish (methyl mercury) Mercury vapors released from metallic mercury in dental amalgams & mercury used in gold mining
  • 38. Mercury • The developing brain is extremely sensitive to methyl mercury • Lipid solubility of methyl mercury and metallic mercury facilitate their accumulation in the brain, disturbing neuromotor, cognitive, and behavioral fxns • There are serious concerns about the effects of chronic low-level exposure to methyl mercury in food exposure of the fetus to high levels of mercury in utero Minamata disease (cerebral palsy, deafness, and blindness)
  • 39. Arsenic • Interfere with several aspects of cellular metabolism, leading to toxicities most prominent in GI tract, nervous system, skin, and heart • Sources: – Naturally occurring in soils and water & is used in products such as wood preservers, herbicides and other agricultural products – Mines and smelting industries – Chinese and Indian herbal medicine • Large concentrations of inorganic arsenic are present in ground water in countries such as Bangladesh, Chile, and China “The poison of kings and the king of poisons”
  • 40. Arsenic Most toxic forms of arsenic are the trivalent compounds: arsenic trioxide, sodium arsenite, and arsenic trichloride Causes acute GI, cardiovascular, and CNS toxicities that are often fatal Interference with mitochondrial oxidative phosphorylation Also has pleiotropic effects on the activity of a number of other enzymes and ion channels, and these too may contribute to certain toxicities
  • 41. Arsenic • Usually occur 2 to 8 weeks after exposure • Paresthesias, numbness, and pain Neurologic effects • Hyperpigmentation and hyperkeratosisSkin changes • The most serious consequence of chronic exposure • Particularly of the lungs, bladder and skin • Arsenic-induced skin tumors - often multiple and usually appear on the palms and soles Increased risk for the development of cancers • Chronic exposure to arsenic in drinking water Non-malignant respiratory disease
  • 42. Cadmium • Preferentially toxic to kidneys and lungs through increased production of reactive oxygen species • Sources: Pollutant generated by mining, electroplating, and production of nickel-cadmium batteries Can contaminate the soil and plants directly or through fertilizers and irrigation water Food is the most important source of cadmium exposure for the general population
  • 43. Cadmium • Principal toxic effects of excess cadmium • caused by necrosis of alveolar epithelial cells Obstructive lung disease • may progress to end-stage renal disease Renal tubular damage • associated with calcium loss Skeletal abnormalities • combination of osteoporosis and osteomalacia • associated with renal disease “Itai-itai” • associated with an elevated risk of lung cancerLung cancer
  • 45. Occupational Health Risks • Consequence of work-related accidents and illnesses • Work-related accidents are the biggest occupational health problem in developing countries • Work-related diseases are more frequent in industrialized countries
  • 47. Occupational Health Risks • Organic solvents – Chloroform and carbon tetrachloride found in degreasing and dry cleaning agents and paint removers – Cause dizziness and confusion, leading to CNS depression and even coma – Lower levels are toxic for the liver and kidneys – Exposure of rubber workers to benzene and 1,3- butadiene increases the risk of leukemia • Polycyclic hydrocarbons – Released during the combustion of fossil fuels, particularly when coal and gas are burned at high temperatures – In tar and soot – Among the most potent carcinogens, and industrial exposures have been implicated in the dev’t of lung and bladder cancer
  • 48. Occupational Health Risks • Organochlorines – Synthetic lipophilic products that resist degradation – Pesticides include DDT (dichlorodiphenyltrichloroethane), lindane, aldrin, and dieldrin – Nonpesticide organochlorines include polychlorinated biphenyls (pcbs) and dioxin (tcdd; 2,3,7,8-tetrachlorodibenzo-p- dioxin) – Organochlorines disrupt hormonal balance because of antiestrogenic or antiandrogenic activity – Dioxins and pcbs - folliculitis and chloracne (acne, cyst formation, hyperpigmentation, and hyperkeratosis)
  • 49. Occupational Health Risks • Mineral dusts – Chronic, non-neoplastic lung disease = PNEUMOCONIOSIS – Exposures to coal dust (e.G., Mining of hard coal), silica (e.G., Sandblasting, stone cutting), asbestos (e.G., Mining, fabrication, insulation work), and beryllium (e.G, mining, fabrication) • Vinyl chloride – Synthesis of polyvinyl resins leads to the development of angiosarcoma of the liver • Bisphenol A – Synthesis of polycarbonate food and water containers and of epoxy resins that line almost all food bottles and cans – Long been known as a potential endocrine disruptor
  • 51. Effects of Tobacco Most readily preventable cause of death in humans Cigarette smoking, “snuff”, “2nd hand smoke” 30% of all smokers worldwide live in China, 10% live in India Cause 90% of lung cancers Tobacco contains between 2000 and 4000 substances, more than 60 of which have been identified as carcinogens
  • 54. Smoking and Lung Cancer • Direct irritant effect on the tracheobronchial mucosa • Inflammation and increased mucus production (bronchitis) • Causes the recruitment of leukocytes to the lung, with increased local elastase production and subsequent injury to lung tissue, leading to emphysema • Polycyclic hydrocarbons and nitrosamines • Risk of developing lung cancer is related to the number of pack years or cigarettes smoked per day
  • 56. Smoking is linked to many other malignant and nonmalignant disorders that affect numerous organ systems Maternal smoking increases risk of abortion, premature birth, and intrauterine growth retardation
  • 58. Effects of Alcohol • Excessive amounts alcohol causes serious physical and psychological damage • Alcohol abuse is a far more widespread hazard and claims many more lives –Drunken driving and alcohol-related homicides and suicides –Consequence of cirrhosis of the liver
  • 59. Alcohol Concentration in the Blood • 80 mg/dl = legal definition of drunk driving – After 3 standard drinks, about three (12 ounce) bottles of beer, 15 ounces of wine, or 4 to 5 ounces of 80 proof distilled spirits • 200 mg/dl = drowsiness occurs • 300 mg/dl = stupor • Higher levels = coma with possible respiratory arrest • Rate of metabolism affects blood alcohol level • Chronic alcoholics can tolerate levels of up to 700 mg/dl due to accelerated ethanol metabolism
  • 60. Metabolism of Alcohol • Absorbed unaltered • Metabolized by 3 enzyme systems: – CYP2E1 – Alcohol Dehydrogenase (ADH) – Catalase • Acetaldehyde – acted upon by Aldehyde Dehydrogenase to form Acetic acid
  • 61. Metabolites of Alcohol • Acetaldehyde – Responsible for some of the acute effects of alcohol and for the development of oral cancers – ALDH2*2 gene = low ALDH activity • Cannot tolerate alcohol, experiencing nausea, flushing, tachycardia, and hyperventilation • NADH/NAD – Increased NADH & decreased NAD = fatty liver & lactic acidosis • ROS – Produced by CYP2E1 – Lipid peroxidation of plasma membrane – Causes release of endotoxin from enteric bacteria = TNF & other cytokines resulting to hepatic damage
  • 62. Adverse Effects of Alcohol Acute alcoholism • Mainly on the CNS, but it may induce hepatic and gastric changes that are reversible if alcohol consumption is discontinued • Fatty change or hepatic steatosis • Acute gastritis and ulceration • Disordered cortical, motor, intellectual behavior & depressed, including those that regulate respiration. Respiratory arrest
  • 63. Adverse Effects of Alcohol Chronic alcoholism • Significant morbidity and have a shortened life span, related principally to damage to the liver, gastrointestinal tract, CNS, cardiovascular system, and pancreas • Cirrhosis • Thiamine (vitamin B1) deficiency = peripheral neuropathies & Wernicke-Korsakoff Syndrome • Alcoholic cardiomyopathy • Acute and chronic pancreatitis • Fetal alcohol syndrome • Increased incidence of cancer of the oral cavity, esophagus, liver
  • 64. Moderate consumption of Alcohol • 20-30 gm/day, corresponding to approximately 250 ml of wine • ↑ high-density lipoprotein (HDL) levels • Inhibit platelet aggregation • ↓ fibrinogen levels • Light to moderate alcohol consumption = ↑ overall survival as compared to teetotalers and heavy drinkers
  • 65. END OF 1ST PART
  • 66. 2ND PART • Injury byTherapeutic Drugs and Drugs of Abuse • Injury by Physical Agents • Nutritional Diseases
  • 67. INJURY BY THERAPEUTIC DRUGS AND DRUGS OF ABUSE
  • 68. Injury by Therapeutic Drugs (Adverse Drug Reactions) • Adverse drug reactions = untoward effects of drugs that are given in conventional therapeutic settings • Due to direct actions of the drug or to immunologically based hypersensitivity reactions
  • 69. Example of Adverse Drug Reaction
  • 71. Anticoagulants • Warfarin (Vitamin K antagonist) and Dabigatran (direct thrombin inhibitor)
  • 72. Menopausal Hormone Therapy • Previously known as HRT (hormone replacement therapy) • Administration of estrogens together with a progestogen • Counteract symptoms of menopause, could prevent or slow the progression of osteoporosis and reduce the likelihood of myocardial infarction Increased the risk of breast cancer, stroke, and venous thromboembolism and had no effect on the incidence of coronary heart disease Should not be used long term for chronic disease prevention
  • 73. Oral Contraceptives • OCs nearly always contain a synthetic estradiol and a variable amount of a progestin, but some preparations contain only progestins • Inhibiting ovulation or preventing implantation Increased risk of cervical cancer in HPV infected women Threefold to sixfold increased risk of venous thrombosis and pulmonary thromboembolism Increase in cardiovascular diseases in women (>35 yo) who smoke Hepatic adenoma in older women with prolonged use
  • 74. Anabolic Steroids Synthetic versions of testosterone Inhibits production and release of luteinizing hormone & follicle- stimulating hormone by a feedback mechanism Increases the amount of estrogens Stunted growth in adolescents, acne, gynecomastia, and testicular atrophy in males, and growth of facial hair and menstrual changes in women Psychiatric disturbances Increased risk of myocardial infarction. Hepatic cholestasis
  • 75. Acetaminophen • Most commonly used analgesic, toxicity is common • Detoxification in the liver by phase II enzymes • Is excreted in the urine as glucuronate or sulfate conjugates 95% of acetaminophen undergoes detoxification • NAPQI (n-acetyl-p-benzoquinoneimine) is a highly reactive metabolite • When acetaminophen is taken in large doses, unconjugated NAPQI accumulates and causes hepatocellular injury 5% or less is metabolized through CYPs (primarily CYP2E) to NAPQI
  • 76. Acetaminophen • 50% of cases of acute liver failure, with 30% mortality • NAPQI mechanism of injury: • Nausea, vomiting, diarrhea, and sometimes shock, followed in a few days by evidence of jaundice • Centrilobular necrosis that may progress to liver failure 1. Covalent binding to hepatic proteins, which causes damage to cellular membranes and mitochondrial dysfunction 2. Depletion of GSH, making hepatocytes more susceptible to reactive oxygen species-induced injury
  • 78. Aspirin: Acetylsalicylic acid • Acute salicylate overdose causes alkalosis as a consequence of the stimulation of the respiratory center in the medulla • Followed by metabolic acidosis and accumulation of pyruvate and lactate, caused by uncoupling of oxidative phosphorylation and inhibition of the Krebs cycle • Nausea to coma
  • 79. Aspirin • Chronic aspirin toxicity (Salicylism) – Headaches, dizziness, ringing in the ears (tinnitus), hearing impairment, mental confusion, drowsiness, nausea, vomiting, and diarrhea – Acute erosive gastritis, gastric ulceration, gastric bleeding – Bleeding tendency – Analgesic nephropathy = tubulointerstitial nephritis with renal papillary necrosis
  • 81. Injury by Nontherapeutic Agents (Drug Abuse) • Illicit substance • Occasional users of illicit “recreational” drugs suffer no apparent long-term health effects • Acute effects may take a significant toll in the form of accidents, violence, or even fatal drug-related complications • Generally involves the repeated or chronic use of mind-altering substances, beyond therapeutic or social norms, and may lead to drug addiction and overdose, both serious public health problems
  • 83. Cocaine • Extracted from the leaves of the coca plant, and is usually prepared as a water-soluble powder, cocaine hydrochloride • Can be snorted or dissolved in water and injected subcutaneously or intravenously • “Crack” form is far more potent • Intense euphoria and stimulation, making it one of the most addictive drugs – Physical dependence generally does not occur – Psychologic withdrawal is profound & extremely difficult to treat
  • 84. Cocaine • Acute and chronic effects – Tachycardia, hypertension, and peripheral vasoconstriction, may also induce myocardial ischemia – Precipitate lethal arrhythmias – Hyperpyrexia (thought to be caused by aberrations of the dopaminergic pathways that control body temperature) and seizures – Acute decreases in blood flow to the placenta, resulting in fetal hypoxia and spontaneous abortion – Perforation of the nasal septum in snorters – Decreased lung diffusing capacity in those who inhale the smoke – Dilated cardiomyopathy
  • 85. Opiates • Opiate drugs of abuse include synthetic prescription opiates such as oxycodone (oxycontin) and “street drugs,” most notably heroin • An addictive opioid derived from the poppy plant that is closely related to morphine • Even more harmful than that of cocaine • Effects on the CNS are varied and include euphoria, hallucinations, somnolence, and sedation
  • 86. Heroin • Adverse effects • Profound respiratory depression, arrhythmia and cardiac arrest, and severe pulmonary edemaSudden death • Severe edema, septic embolism, granulomasPulmonary injury • S. Aureus, but fungi and a multitude of other organisms have also been implicatedInfections • Abscesses, cellulitis, and ulcerations due to subcutaneous injections, hyperpigmentation over commonly used veinsSkin • Amyloidosis, focal and segmental glomerulosclerosis; both induce proteinuria and the nephrotic syndromeKidneys
  • 87. Amphetamines and Related Drugs Methamphetamine • “speed” or “meth” • stronger effects in the CNS • inhibits presynaptic neurotransmission at corticostriatal synapses, slowing glutamate release • Long-term use leads to violent behaviors, confusion, and psychotic features that include paranoia and hallucinations MDMA • 3,4 methylenedioxymethamphetamine = “Ecstasy” • taken orally • effects, which include euphoria and hallucinogen-like feelings that last 4 to 6 hours • partly attributable to an increase in serotonin release in the CNS • reduces the number of serotonergic axon terminals in the striatum and the cortex, and it may increase the peripheral effects of dopamine and adrenergic agents
  • 88. Marijuana • Most widely used illicit drug globally • “Pot”, “weed” • Leaves of the cannabis sativa plant, which contain the psychoactive substance δ9-tetrahydrocannabinol (THC) • Untoward anecdotal effects allergic or idiosyncratic reactions or possibly related to contaminants in the preparations rather than to the pharmacologic effects of marijuana
  • 89. Marijuana • Beneficial effects of marijuana – treat nausea secondary to cancer chemotherapy and as an agent capable of decreasing pain in some chronic conditions • Distorts sensory perception and impairs motor coordination – acute effects clear in 4 to 5 hours • With continued use cognitive and psychomotor impairments occur a potential cause of automobile accidents • Increases the heart rate and blood pressure, and it may cause angina in a person with coronary artery disease
  • 90. Marijuana • Chronic marijuana smoking – laryngitis, pharyngitis, bronchitis, cough and hoarseness, and asthma-like symptoms have all been described, along with mild but significant airway obstruction • Large number of carcinogens that are also present in tobacco • Smoking a marijuana cigarette, compared with a tobacco cigarette, is associated w/ threefold increase in amount of tar inhaled
  • 91. Other Drugs PCP (phencyclidine, an anesthetic agent) = “OOBE” Vicodin, and ketamine, an anesthetic agent Spray paints, paint thinners, and some glues that contain TOLUENE • Mild to severe dementia • Bizarre and often aggressive behavior that leads to violence or depressed mood and suicidal ideation “Bath salts” • Contain 4-methyl-meth-cathinone and methylenedioxypyrovalerone • Amphetamine-like effects when snorted or eaten • Agitation, psychosis, myocardial infarction, and suicide
  • 93. Mechanical trauma • Type of injury depends on the shape of the colliding object, the amount of energy discharged at impact, and the tissues or organs that bear the impact • Mechanical forces, and the patterns of injury can be divided into abrasions, contusions, lacerations, incised wounds, and puncture wounds • Forensic pathology
  • 94. Thermal Injury • Excessive heat and excessive cold are important causes of injury – Thermal burns – Hyperthermia – Hypothermia
  • 95. Thermal Burns • Caused by fire or by scalding • Consequence of injuries caused by fire and smoke inhalation • Clinical significance of a burn injury: Depth of the burns Percentage of body surface involved Internal injuries caused by the inhalation of hot and toxic fumes Promptness and efficacy of therapy, especially fluid and electrolyte management and prevention or control of wound infections
  • 96. Thermal Burns • According to the depth of the injury Superficial burns • Formerly known as first-degree burns • Confined to the epidermis Partial thickness burns • Formerly known as second-degree burns • Involve injury to the dermis Full-thickness burns • Formerly known as third-degree burns: extend to the subcutaneous tissue • Formerly known as fourth-degree burns: involve damage to muscle tissue underneath the subcutaneous tissue
  • 97. Thermal Burns • Greatest threats to life Shock, sepsis, and respiratory insufficiency • Systemic inflammatory response syndrome = shock • Hypermetabolic state = increased need for nutritional support Burns of more than 20% of the body surface • Pseudomonas aeruginosa • Methicillin-resistant S. Aureus • Candida species Infection • Early excision and grafting of the burn wound Organ system failure resulting from burn sepsis • Inhalation of heated air and noxious gases in the smoke Injury to the airways and lungs
  • 98. Hyperthermia • Prolonged exposure to elevated ambient temperatures • Heat cramps – Loss of electrolytes via sweating – Cramping of voluntary muscles, in association with vigorous exercise, is the hallmark – Heat-dissipating mechanisms are able to maintain normal core body temperature • Heat exhaustion – Most common: hyperthermic syndrome – Prostration and collapse, and it results from a failure of the cardiovascular system to compensate for hypovolemia caused by dehydration – After a period of collapse, which is usually brief, equilibrium is spontaneously re-established if the victim is able to rehydrate
  • 99. Hyperthermia • Heat stroke – Associated with high ambient temperatures, high humidity, and exertion – Thermoregulatory mechanisms fail, sweating ceases, and the core body temperature rises to more than 40°C, leading to multiorgan dysfunction that can be rapidly fatal – Generalized vasodilation, with peripheral pooling of blood and a decreased effective circulating blood volume – Hyperkalemia, tachycardia, arrhythmias, and other systemic effects
  • 100. Hyperthermia • Malignant hyperthermia – Characterized by a “heat-stroke–like” rise in core body temperature and muscle contractures following exposure to common anesthetics due to inherited mutations in RYR1 – Ryanodine receptor 1 (RYR1), which is located in the sarcoplasmic reticulum of skeletal muscle • RYR1 regulates the release of calcium from the sarcoplasm • Heat stroke deranges RYR1 function →calcium to leak into the cytoplasm→muscle contraction and heat production
  • 101. Hypothermia • Prolonged exposure to low ambient temperature • High humidity, wet clothing, and dilation of superficial blood vessels resulting from the ingestion of alcohol hasten the lowering of body temperature • Body temperature of about 90°F (32.2°C): loss of consciousness occurs, followed by bradycardia and atrial fibrillation at lower core temperatures
  • 102. Hypothermia • Hypothermic injury: • Slow chilling may induce vasoconstriction and increase vascular permeability, leading to edema and hypoxia = “trench foot” • Sudden, persistent chilling, the vasoconstriction and increased viscosity of the blood in the local area may cause ischemic injury and degenerative changes in peripheral nerves Direct effects • Mediated by physical disruptions within cells by high salt concentrations caused by the crystallization of intra- and extracellular water Indirect effects • Circulatory changes, which vary depending on the rate and duration of the temperature drop
  • 103. Electrical Injury • Contact with low-voltage currents (i.e., at home and workplace) or high-voltage currents carried by high-power lines or produced by lightning • Two types of injuries: 1. Burns 2. Ventricular fibrillation OR cardiac & respiratory center failure • Depend on the strength (amperage), duration, and path of the electric current within the body
  • 104. Electrical Injury • Voltage in the household and workplace (120 or 220 V) is high enough that with low resistance at the site of contact , sufficient current can pass through the body to cause serious injury, including ventricular fibrillation • Alternating current (AC) – Type supplied to most homes – Induces tetanic muscle spasm, so that when a live wire or switch is grasped, irreversible clutching is likely to occur, prolonging the period of current flow – Extensive electrical burns and spasm of the chest wall muscles, producing death from asphyxia
  • 105. Electrical Injury Currents generated from high-voltage sources • Cause similar damage The large current flows generated are more likely to produce paralysis of medullary centers and extensive burns • Lightning Magnetic fields and microwave radiation • Produce burns, usually of the skin and subjacent connective tissue when sufficiently intense
  • 106. Ionizing Radiation Injury • Energy that travels in the form of waves or high-speed particlesRadiation • Ex: UV and infrared light, microwave, and sound waves • Can move atoms in a molecule or cause them to vibrate, but is not sufficient to displace bound electrons from atoms Nonionizing Radiation • Has sufficient energy to remove tightly bound electrons • X-rays and gamma rays, high-energy neutrons, alpha particles and beta particles Ionizing Radiation • Fibrosis, mutagenesis, carcinogenesis, and teratogenesisCauses:
  • 107. Ionizing Radiation Injury • Units of radiation Curie (Ci) an expression of the amount of radiation emitted by a source Gray (Gy) is a unit that expresses the energy absorbed by the target tissue per unit mass Sievert (Sv) is a unit of equivalent dose that depends on the biologic rather than the physical effects of radiation
  • 108. Ionizing Radiation Injury • Biologic effects of Radiation determinants • Cumulative effect = fractioned dosesRate of delivery • Body area of exposure = higher doses tolerated if limited area is exposedField size • rapidly dividing cells are more vulnerable to injury than are quiescent cellsCell proliferation • production of reactive oxygen species Oxygen effects and hypoxia • Damage to endothelial cells = narrowing or occlusion of blood vesselsVascular damage
  • 114. Malnutrition • Consequence of inadequate intake of proteins and calories, or deficiencies in the digestion or absorption of proteins • Loss of fat and muscle tissue, weight loss, lethargy, and generalized weakness • Developing nations – malnutrition, starvation, obesity
  • 115. Dietary insufficiency • Appropriate diet: • Primary malnutrition – one or all of these components are missing from the diet • Secondary malnutrition – malnutrition results from malabsorption, impaired utilization or storage, excess loss, or increased need for nutrients sufficient energy amino acids and fatty acids • to be used as building blocks for synthesis of proteins and lipids vitamins and minerals • function as coenzymes or hormones in vital metabolic pathways • or, as in the case of calcium and phosphate, as important structural components
  • 116. Conditions that lead to malnutrition Poverty Infections Acute and chronic illnesses Chronic alcoholism Ignorance and failure of diet supplementation Self-imposed dietary restriction Other causes
  • 117. Protein Energy Malnutrition (PEM)• Determined by body mass index – Weight in kilograms divided by height in meters squared – Normal range 18.5 to 25 kg/m2 • Thickness of skin folds – fat stores • Circumference of mid-arm – muscle mass • Serum proteins – visceral protein • 2 spectrums of PEM syndromes: Marasmus • somatic compartment, represented by proteins in skeletal muscles Kwashiorkor • visceral compartment, represented by protein stores in the visceral organs, primarily the liver
  • 118. Marasmus • Weight falls to 60% of normal for sex, height, and age • Growth retardation and loss of muscle • Visceral protein compartment minimally depleted • Serum albumin levels are either normal or only slightly reduced • Extremities are emaciated • Anemia & immune deficiency
  • 119. Kwashiorkor • Protein deprivation is relatively more severe than the deficit in total calories • Severe depletion of the visceral protein compartment • Hypoalbuminemia = generalized or dependent edema • Skin lesions = flaky paint • Hair changes = flag sign • Fatty liver, apathy, listlessness, and loss of appetite • Defects in immunity and secondary infections
  • 120. Cachexia • PEM in AIDS or advanced cancers • Extreme weight loss, fatigue, muscle atrophy, anemia, anorexia, and edema • Mediators secreted by tumors and during chronic inflammatory reactions Proteolysis- inducing factor • glycosylated polypeptide Lipid-mobilizing factor • TNF and IL-6
  • 122. Anorexia Nervosa and Bulimia Anorexia nervosa • Highest death rate of any psychiatric disorder • Altered serotonin metabolism • Similar to those in severe PEM • Amenorrhea • Decreased thyroid hormone release • Bone density is decreased • Cardiac arrhythmia & sudden death Bulimia • Large amounts of food, principally carbohydrates, are ingested, only to be followed by induced vomiting • Menstrual irregularities • Frequent vomiting and the chronic use of laxatives and diuretics • Electrolyte imbalances • Pulmonary aspiration • Esophageal and gastric rupture • Cardiac arrhythmia & sudden death
  • 123. Vitamin Deficiencies • Thirteen vitamins are necessary for health – Fat soluble and water soluble • Vitamins A, D, E, and K are fat-soluble • Fat-soluble vitamins are more readily stored in the body • Endogenous synthesis of vitamins: D, K & niacin • Deficiencies: – Primary = dietary insufficiency – Secondary = disturbances in absorption, transport, storage or metabolism
  • 124. Vitamin A • Retinol (alcohol), retinal (aldehyde), and retinoic acid (acid) • Fat soluble • Functions: Maintenance of normal vision Cell growth and differentiation Host resistance to infections Adipogenesis and fatty acid metabolism
  • 125. Vitamin A Deficiency • Occurs due to: undernutrition or malabsorption of fats • Night blindness • Epithelial metaplasia and keratinization – Xerophthalmia – Bitot’s spots – Keratomalacia – Squamous metaplasia Toxicity • Liver = polar bear, whales, sharks and tuna • Acute – Headache, dizziness, vomiting, stupor, and blurred vision, pseudotumor cerebri • Increased osteoclast activity • Teratogenic effect of retinoids
  • 126. Vitamin D • Endogenously synthesized fat soluble vitamin; deep-sea fish, plants, and grains are dietary sources • Cholecalciferol (vitamin D3) • Maintenance plasma levels of calcium and phosphorus – Metabolic functions – Bone mineralization – Neuromuscular transmission Functions: Stimulation of intestinal calcium absorption Stimulation of calcium reabsorption in the kidney Interaction with PTH in the regulation of blood calcium Mineralization of bone – osteocalcin
  • 127. Vitamin D Deficiency – insufficient diet and limited sun exposure – Rickets • Craniotabes • Frontal bossing • Rachitic rosary • Pigeon breast deformity • Bowing of the legs – Osteomalacia • Gross fractures or microfractures – Hypocalcemic tetany – Osteoporosis (vitamin D insufficiency) Vit D supplements – increased lymphocyte count, enhanced clearance of MTB in sputum Toxicity – Megadoses of oral vitamins – Not from prolonged exposure to sunlight – Metastatic calcifications – Bone pain – Hypercalcemia
  • 128. Vitamin C • Water soluble vitamin • Ascorbic acid • Entirely dependent on the diet for this nutrient • Milk and some animal products (liver, fish) and is abundant in a variety of fruits and vegetables • Functions: Activation of prolyl and lysyl hydroxylases Hydroxylation of procollagen Promotes secretion of procollagen Antioxidant properties – direct and indirect
  • 129. Vitamin C • Vitamin excess – Mild antihistamine action =Tx for common colds – Toxicities are rare • Iron overload due to increased absorption • Hemolytic anemia in G6PD deficiency patients • Calcium oxalate stones
  • 131. Obesity • An accumulation of adipose tissue that is of sufficient magnitude to impair health • ↑ Incidence type 2 diabetes, dyslipidemias, cardiovascular disease, hypertension, and cancer • BMI measurements 18.5 to 25 kg/m2 Normal BMI range 25 to 30 kg/m2Overweight > 30 kg/m2Obese
  • 132. Obesity • Distribution of the stored fat – Central, or visceral, obesity – Subcutaneous obesity • Refined sugars, sweetened beverages, and vegetable oils • Disease of caloric imbalance – Intake of calories ≥ calorie consumption – Genetic influences play an important role in weight control – But the interaction between multiple factors
  • 133. Obesity • Neurohumoral control of energy balance – Peripheral or afferent system – generates signals Leptin PeptideYY Adiponectin Insulin Ghrelin – Arcuate nucleus in hypothalamus - processes and integrates neurohumoral signals • POMC (pro-opiomelanocortin) and CART (cocaine and amphetamine-regulated transcripts) neurons • NPY (neuropeptideY) and AgRP (Agouti-Related Peptide) neurons – Efferent system • Anabolic – control food intake • Catabolic – control energy expenditure
  • 136. Components of the Afferent System • Regulates appetite and satiety • Leptin – Product of the ob gene – 16-kd hormone synthesized by fat cells – Signal for energy sufficiency = leptin secretion is stimulated when fat stores are abundant – Stimulates POMC/CART neurons that produce anorexigenic neuropeptides – Stimulates physical activity, heat production, and energy expenditure • Adiponectin (guardian angel against obesity) – Hormone is produced mainly by adipocytes – Directs fatty acids to muscle for their oxidation – Decreases the influx of fatty acids to the liver & decreases glucose production – Increase in insulin sensitivity – Inactivates acetyl coa carboxylase thru binding with adipor1 and R2
  • 137. Components of the Afferent System • Gut hormones • Ghrelin – Produced in the stomach and arcuate nucleus of the hypothalamus – The only known gut hormone that is orexigenic effect – Likely to stimulate NPY/AgRP neurons – Post-prandial level attenuation = overeating • PYY – Secreted by endocrine cells in the ileum & colon – Reduces energy intake – Stimulates POMC/CART neurons • Amylin – Peptide secreted with insulin by β cells – Reduces food intake and weight gain – Stimulates POMC/CART neurons
  • 139. Consequences of Obesity • Metabolic syndrome – Visceral adiposity, insulin resistance, hyperinsulinemia, glucose intolerance, hypertension, hypertriglyceridemia, and low HDL cholesterol • Insulin resistance and hyperinsulinemia • ↑ Risk coronary artery disease • Nonalcoholic fatty liver disease • Cholelithiasis (gallstones) • Hypoventilation syndrome (Pickwickian syndrome) – Hypersomnolence – Sleep apnea – Cor pulmonale • Osteoarthritis
  • 140. Obesity and Cancer • ↑ risk for cancers of the esophagus, pancreas, colon and rectum, breast, endometrium, kidney, thyroid, and gallbladder • Possibly due to the following: Elevated insulin levels Effects on steroid hormone Low adiponectin levels = Elevated insulin Pro- inflammatory state
  • 141. Diet and Cancer • Incidence of cancer varies with geographic areas • Environmental factors clearly play a role including diet • There are few mechanisms that link diets and specific types of cancer • Aspects of diet concerned with Carcinogenesis – Content of exogenous carcinogens – Endogenous synthesis of carcinogens from dietary components – Lack of protective factors • Exogenous carcinogens – Aflatoxin = liver CA – Food additives, pesticides, artificial sweeteners • Endogenous carcinogens – Gastric CA – Nitrosamines – Nitrosamides • High animal fat and low fiber – Colon CA – Breast CA • Low vitamins – Vitamin C, β carotene, selenium,Vitamin D
  • 142. Diet and Atherosclerosis • Association of dietary cholesterol and saturated animal fats with development of atherosclerosis • Role that caloric restriction and special diets may play in the control of body weight and prevention of cardiovascular disease • Activation of sirtuins and on lowering of insulin and IGF-1 levels
  • 143. Diet and Atherosclerosis • Focus on eating an enjoyable and healthy diet Rich in fish Vegetables Whole grains Fruits Olive and peanut oils Complex carbohydrates Low salt
  • 144. END

Hinweis der Redaktion

  1. Limiting the value of establishing rigid “safe levels” for entire populations. Cut-offs are useful for comparative studies of the effects of harmful agents between specific populations, and for estimating risk of disease in heavily exposed individuals
  2. Xenobiotic metabolism. A, Xenobiotics can be metabolized to nontoxic metabolites and eliminated from the body (detoxification). B, Xenobiotic metabolism may also result in the formation of a reactive metabolite that is toxic to cellular components. If repair is not effective, short- and long-term effects develop.
  3. more heavily in cities and in proximity to heavy industry
  4. such as legionnaires disease, viral pneumonia, and the common cold
  5. Effects of lead poisoning in children related to blood levels.
  6. Pathologic features of lead poisoning in adults. microcytic hypochromic anemia stemming from the suppression of hemoglobin synthesis. δ-aminolevulinic acid dehydratase and ferrochelatase inhibition
  7. To protect against potential fetal brain damage, the CDC has recommended that pregnant women avoid consumption of fish known to contain high levels of mercury.
  8. The effects of smoking on survival. The study compared age-specific death rates for current cigarette smokers with that of individuals who never smoked regularly (British Doctors Study). Measured at age 75, the difference in survival between smokers and nonsmokers is 7.5 years.
  9. The risk of lung cancer is determined by the number of cigarettes smoked
  10. Summary of the adverse effects of smoking: those that are more common are in boldface.
  11. caused by a fivefold to 10-fold induction of liver CYPs (discussed later). The effects of alcohol also vary by age, sex, and body fat.
  12. providing a possible basis for protective effects against coronary heart disease
  13. Adverse drug reaction. Skin pigmentation caused by minocycline, a long-acting tetracycline derivative. A, Diffuse blue-gray pigmentation of the forearm; B, Deposition of drug metabolite/iron/melanin pigment particles in the dermis.
  14. may develop in persons who take 3 gm or more daily for long periods of time for treatment of chronic pain or inflammatory conditions
  15. Cracks = Crystallization of the pure alkaloid yields nuggets
  16. (1) the pharmacologic action of the agent, (2) reactions to the cutting agents or contaminants, (3) hypersensitivity reactions to the drug or its adulterants (quinine itself has neurologic, renal, and auditory toxicity), and (4) diseases contracted incident to the use of contaminated needles
  17. such as inability to judge time, speed, and distance,
  18. (as when the skin is wet)
  19. Collision of electrons with other molecules releases electrons in a reaction cascade, referred to as ionization
  20. Effects of ionizing radiation on DNA and its consequences. The effects on DNA can be direct, or most importantly, indirect, through free radical formation.
  21. Radiation-induced chronic vascular injury with subintimal fibrosis occluding the lumen.
  22. , in the form of carbohydrates, fats, and proteins, for the body’s daily metabolic needs;
  23. Homeless persons, aged individuals, and children of the poor often suffer from PEM as well as trace nutrient deficiencies. In poor countries, poverty, crop failures, livestock deaths, and drought, often in times of war and political upheaval, create the setting for the malnourishment of children and adults. PEM increases susceptibility to many common infectious diseases. Conversely, infections have a negative effect on nutrition, thus establishing a vicious cycle. The basal metabolic rate becomes accelerated in many illnesses resulting in increased daily requirements for all nutrients. Failure to recognize these nutritional needs may delay recovery. PEM is often present in patients with wasting diseases, such as advanced cancers and AIDS (discussed later). Alcoholic persons may sometimes suffer PEM but more frequently have deficiencies of vitamins, especially thiamine, pyridoxine, folate, and vitamin A, as a result of poor diet, defective gastrointestinal absorption, abnormal nutrient utilization and storage, increased metabolic needs, and an increased rate of loss. A failure to recognize the likelihood of thiamine deficiency in persons with chronic alcoholism may result in irreversible brain damage (e.g., Wernicke encephalopathy andKorsakoff psychosis, discussed in Chapter 28). Even the affluent may fail to recognize that infants, adolescents, and pregnant women have increased nutritional needs. Ignorance about the nutritional content of various foods is also a contributing factor. Some examples are: iron deficiency in infants fed exclusively artificial milk diets; polished rice used as the mainstay of a diet may lack adequate amounts of thiamine; lack of iodine from food and water in regions removed from the oceans, unless supplementation is provided. Anorexia nervosa, bulimia, and less overt eating disorders affect many individuals who are concerned about body image and are obsessed with body weight (anorexia and bulimia are discussed later). include gastrointestinal diseases and malabsorption syndromes, genetic diseases, specific drug therapies (which block uptake or utilization of particular nutrients), and inadequate total parenteral nutrition.
  24. high in impoverished countries of Southeast Asia protein-losing enteropathies, the nephrotic syndrome, or after extensive burns; fad diets or replacement of milk by rice-based beverages relative sparing of subcutaneous fat and muscle mass
  25. Hypokalemia
  26. Hypocalcemia stimulates secretion of parathyroid hormone (PTH) Hypophosphatemia directly activates 1α-hydroxylase
  27. Excess adiposity (obesity) and excess body weight in which fat accumulates in the trunk and in the abdominal cavity (in the mesentery and around viscera), is associated with a much higher risk for several diseases Diffuse distribution of fat
  28. Excess adiposity (obesity) and excess body weight in which fat accumulates in the trunk and in the abdominal cavity (in the mesentery and around viscera), is associated with a much higher risk for several diseases Diffuse distribution of fat
  29. Regulation of energy balance. Adipose tissues generate afferent signals that influence the activity of the hypothalamus, which is the central regulator of appetite and satiety. These signals decrease food intake by inhibiting anabolic circuits, and enhance energy expenditure through the activation of catabolic circuits. PYY, Peptide YY.
  30. Neurohumoral circuits in the hypothalamus that regulate energy balance. Shown are POMC/CART anorexigenic neurons and NPY/AgRP orexigenic neurons in the arcuate nucleus of the hypothalamus, and their pathways
  31. Obesity, metabolic syndrome, and cancer. Obesity and excessive weight are precursors of the metabolic syndrome, which is associated with insulin resistance, type 2 diabetes, and hormonal changes. Increases in insulin and IGF-1 (insulin-like growth factor-1) stimulate cell proliferation and inhibit apoptosis and may contribute to tumor development. IGF, Insulin-like growth factor; IGFBP, insulin-like growth factor-binding protein; SHBG, sex hormone-binding globulin.
  32. Calorie-restricted animals = less age-related decline in immunologic functions, less oxidative damage, & greater resistance to carcinogenesis