Environmentalpathology PDF

05/03/2019
ENVIRONMENTAL PATHOLOGY
Peran biologi dlm model ekologi kesehatan berbasis populasi
Muhammad Farid Dimjati Lusno

Departemen Kesehatan Lingkungan Fakultas Kesehatan Masyarakat
Universitas Airlangga - 2019
Global Climate Change
• Human activity a major contributor
• Increases of carbon dioxide, methane, and

ozone  main ingredients of the
greenhouse effect  along with water
vapor acts like a blanket  absorb energy
radiated from the earth’s surface
• Recent increases due to combustion of

hydrocarbons in automobiles and energy
plants
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• Present concentration of atmospheric

CO2 = 370 ppm
 Expected to increase to 500 – 1200

ppm at the end of the century
 Large scale deforestation a major

contributor  decreased carbon
sequestration by trees
• Effects of global warming:
• Loss of reflective snow and ice  increased

heat absorption
• Greater evaporation from bodies of water and
transpiration from trees  increased water
vapor in the atmosphere
• Thawing of arctic tundra  large releases of
stored CO2 and methane
• Diminished growth of diatoms  decreased
sequestration of CO2
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Global Climate Change: Health Impacts
Global Climate Change: Health Impacts
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Toxicity of Chemicals & Physical Agents
Toxicology
• Science of poisons
• Studies the distribution, effects, and

mechanisms of action of toxic agents
• Includes the study of the effects of

physical agents such as radiation and
heat
Basic Principles:
1. The definition of poison is not

straightforward. It is a quantitative
concept strictly dependent on dosage.
2. Xenobiotics are exogenous chemicals in the

environment (air, water, food, and soil)
that may be absorbed into the body.
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Xenobiotic
Metabolism
Basic Principles:
1. Chemicals may be excreted in urine,

feces, or eliminated in expired air, or
may accumulate in tissues (e.g. Bone,
fat, brain).
2. Chemicals may act at the site of entry

or at other sites following transport
through blood.
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Basic Principles:
 Most solvents and drugs are lipophilic

 facilitate transport through blood
by lipoproteins and entry into cells.
 The most important catalyst in the

metabolism of xenobiotics is the
cytochrome P450 enzyme system.
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Cytochrome P450 enzyme system
• Primarily in endoplasmic reticulum

of liver but also present in skin, lungs,
GIT, and other organs
• Catalyze reactions that either:

• Detoxify xenobiotics
• Activate xenobiotics into active
compounds  cause cellular injury
• Production of reactive oxygen species

common to both reactions  cellular
damage
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• Great variation in activity of CYPs

among individuals due to:
1. Genetic polymorphism in specific
CYPs
2. Exposure to drugs or chemicals
that induce or diminish activity
 Inducers: environmental
chemicals, drugs, smoking,
alcohol, hormones
 Decrease activity: fasting or
starvation
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Environmental Pollution: Air Pollution
Outdoor Air Pollution
• Six major pollutants: sulfur dioxide,

carbon monoxide, ozone, nitrogen
dioxide, lead, and particulate matter 
collectively produce SMOG (smoke and
fog)
• Lungs bear the brunt of adverse effects

but other organs may be affected.
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Outdoor Air Pollution – Ozone
• UV radiation + O2 in stratosphere =
ozone (O3)
• Two types:
1. Stratospheric ozone (ozone layer)
 “good ozone”  absorbs the most
dangerous UV radiation from sun
 Decreased during last 30 years due
to use of aerosols
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• Two types:
2. Groundlevel ozone
 Ozone that accumulates in the lower
atmosphere
 Formed by reaction of nitrogen oxides
and volatile organic compounds in the
presence of sunlight
 Due to industrial emissions and motor
vehicle exhaust
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• Toxicity due to production of free radicals

 injure epithelial cells  release of
inflammatory mediators
• Other agents (e.g. Sulfur dioxide from

power plants, copper smelters, paper
mills)  released into the air  combine
with ozone to produce sulfuric acid
 Acid rain
 Burning sensation in nose and throat;
respiratory symptoms
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Outdoor Air Pollution – Particulate Matter
• Known as soot
• Emitted by:
1. coal and oilfired power plants
2. Industrial processed burning fuels
3. Diesel exhaust
• Fine or ultrafine particles < 10 um in
diameter the most harmful  inhaled 
phagocytosed by macrophages &
neutrophils  release inflammatory
mediators (e.g. Macrophage inflammatory
protein 1α and endothelins)
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who.int/gho/phe/outdoor_air_pollution/en/
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Outdoor Air Pollution – Carbon Monoxide

• Nonirritating, colorless, tasteless, odorless
gas
• Produced by incomplete oxidation of
carbonaceous materials
• Low levels found in ambient air  contribute
to impaired respiratory function but not life-
threatening
• Important cause of accidental and suicidal
death
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• Small, closed garage  lethal coma within

5 minutes
• If hemoglobin 20% - 30% saturated with
CO  systemic hypoxia
• If 60% - 70% saturated  unconsciousness
and death
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• Acute poisoning:
 Due to accidental exposure or suicide

attempt
 Characteristic cherryred color of skin
and mucus membranes in lightskinned
individuals  due to high levels of
carboxyhemoglobin
 Morphologic changes due to systemic
hypoxia; nonspecific
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• Chronic poisoning:
 Slowly developing hypoxia  ischemic changes in

the CNS (especially basal ganglia and lenticular
nuclei)
 Cessation of exposure  recovery but with

permanent neurologic sequelae (impairment of
memory, vision, hearing, and speech)
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Indoor Air Pollution
• Common pollutants:
1. Tobacco smoke – most common
2. Carbon monoxide
3. Nitrogen dioxide
4. Asbestos
5. Volatile substances containing poly
cyclic aromatic hydrocarbons from
cooking oils and coal burning
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Environmental Pollution: Metals
Lead
• Exposure occurs through contaminated

air, food, and water
• Major sources in the environment: house
paints, gasoline, mining, foundries,
batteries
• Other sources: toys
• Subclinical poisoning may occur in
children exposed to levels < 10 ug/dL
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Lead
• Majority of absorbed lead (80% 85%)

incorporated into bone and developing
teeth  competes with calcium
• High levels  CNS disturbances in adults

(peripheral neuropathies) and children
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Lead – Effects:
• Inhibition of neurotransmitters due to

disruption of calcium homeostasis
• Interference with normal

remodelling of cartilage and
primary bone trabeculae in
epiphyses of children.
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Lead – Effects:
Blood and bone marrow

• Inhibition of δaminolevulinic acid
dehydratase & ferrochelatase  inhibit
heme synthesis  microcytic,
hypochromic anemia with mild
hemolysis
• Characteristic; occurs early 
appearance of ringed sideroblasts
Basophilic stippling of red cells
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RBC with
basophilic
stipplings (arrow)
indicating
clustering of
ribosomes.
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Lead – Effects:
Brain
• Brain damage prone to occur in

children  sensory, motor, intellectual,
and psychologic impairments
• Adults  peripheral demyelinating
neuropathy involving motor nerves of
the most commonly used muscles
 Extensor muscles of wrist & fingers
(wristdrop)  peroneal muscles
(footdrop)
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Lead – Effects:
Gastrointestinal Tract
• Extremely severe, poorly localized

abdominal pain
Kidneys
• Proximal tubular damage

• Chronic  interstitial fibrosis  renal
failure
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Mercury
• Three forms of mercury:

1. Metallic mercury (elemental mercury)
2. Inorganic mercury compounds
(mercuric chloride)
3. Organic mercury (methyl mercury)
• Main sources at present:

1. Contaminated fish (methyl mercury)
2. Mercury vapors released from dental
amalgams
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Mercury
• Minamata disease
 Cerebral palsy, deafness, blindness,
mental retardation in children exposed
in utero
 Methyl mercury metallic mercury
lipid soluble  facilitate brain
accumulation  impaired cognitive,
neuromotor, and behavioral
function
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Arsenic
• “poison of kings and the king of poisons”

• Found naturally in soils and water
• Used in products such as wood preservers,
herbicides, and other agricultural
products
• Present in Chinese and Indian herbal
medicine
• Arsenic trioxide – used in the treatment of
acute promyelocytic leukemia
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Arsenic Toxic Effects
• Acute toxic effects due to interference with

mitochondrial oxidative phosphorylation
 Severe disturbances of GIT, cardio
vascular system, and CNS
• Most serious consequence of chronic

exposure is increased risk for development
of cancers (e.g. Basal and squamous cell Ca
of skin)
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Cadmium
• Relatively a modern problem
• Can contaminate the soil and plants

directly or through fertilizers and
irrigation water
• Most important source for the general

population is food
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Occupational Health Risks
Organic solvents
• Sources:
• Degreasing & dry cleaning agents,
and paint removers  chloroform and
carbon tetrachloride
 Acute exposure: dizziness and
confusion  CNS depression 
coma
 Low levels toxic to liver and
kidneys
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Organic solvents
• Sources:
• Rubber workers  benzene and 1,3
butadiene
 Increased risk of leukemia
 Benzene oxidized by hepatic CYP2E1
 disrupt differentiation of
hematopoietic cells in bone marrow
 marrow aplasia (dosedependent)
 increased risk of acute myeloid
leukemia
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Polycyclic hydrocarbons
• Released during combustion of fossil

fuels, especially when coal and gas are
burned at high temperatures (steel
foundries); also present in tar and soot
• Among the most potent carcinogens
• Lung, bladder, and scrotal cancer
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Organochlorines
• Synthetic lipophilic substances that resist

degradation
• Sources:
1. Pesticides – DDT
2. Nonpesticides – polychlorinated
biphenyls (PCBs) and dioxin
• Endocrine disruptors  antiestrogen or

antiandrogen activity
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Organochlorines
• Dioxins and PCBs

 Folliculitis
 Chloracne – dermatosis; acne, cyst
formation, hyperpigmentation, and
hyperkeratosis around face and
behind ears
 Liver and CNS abnormalities
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Multiple cysts were

present:
(A) on the face and (B) in
the auricular areas, which
normally are not affected
in patients with common
acne. Only a few cysts
were present on the
patient's back in summer
1998 (C), whereas 1 year
later (D) the patient's back
was covered with many
severely inflamed cysts.
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Mineral Dusts
• Cause chronic nonneoplastic lung

diseases called pneumoconioses
• Sources:
• Mining of hard coal  coal dust
• Sandblasting, stone cutting, etc. 
silica
• Mining, fabrication, insulation work
 asbestos, beryllium
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Coal Worker’s
Pneumoconiosis
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Tobacco
• Most common exogenous cause of human

cancer
 Cigarette smoking – main culprit
 Smokeless tobacco (snuff, chewing
tobacco, etc.)  oral cancer
 Secondhand smoke  lung cancer
in nonsmokers
• Most preventable cause of human death.
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Tobacco
• Cessation of smoking –
 Significantly reduces within 5 years

the overall mortality and the risk of
death from CV diseases
 Decreases lung cancer mortality by

21% within 5 years
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Tobacco
• Most common diseases caused by cigarette smoking

involve the lungs and include:
1. Emphysema
2. Chronic bronchitis
3. Chronic obstructive pulmonary disease
• 4. Lung cancer
Cigarette smoking increases risk for: atherosclerosis,

MI, cancers (lips, mouth, pharynx, esophagus,
pancreas, bladder, kidney, and cervix)
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Polycyclic
SMOKING Cigarette smoke hydrocarbons
& nitrosamines
Direct irritant Recruitment Increase

CYPs water
effect of leukocytes
solubility of
to lungs carcinogens
Electrophilic
Increased intermediates
of CYPs Excretion
local elastase
Tracheo
production
bronchial
mucosa
Form DNA
Injury to lung adducts
tissue
Mutations in
Bronchitis Emphysema
Kras and p53
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SMOKING
Decreased
Increased threshold for
platelet ventricular
aggregation fibrillation
Increased Decreased
oxygen demand myocardial
oxygen supply
Significant lung disease

Hypoxia due to CO
content of cigarette
smoke
Atherosclerosis and M.I.
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Maternal smoking
increases the risk of:
•Spontaneous abortions
•Preterm births
•IUGR
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Passive smoke inhalation
• Relative risk of lung cancer ~ 1.3x higher

than those not exposed
• Increased risk of coronary AS and fatal M.I.
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ALCOHOL
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Alcohol
• Consumption in moderate amounts

generally not injurious
• Ethanol absorbed unaltered in the stomach

and small intestines  distributed to all
tissues and fluids of the body in direct
proportion to the blood level
 < 10% excreted unchanged in urine,
sweat, and breath  amount exhaled is
proportional to blood level
 80 mg/dL in blood – legal definition of
DUI in the U.S.
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Alcohol
• Most of the alcohol in the blood is bio

transformed to acetaldehyde in the liver by
three enzyme systems:
1. Alcohol dehydrogenase (ADH) – main;

cytosol of hepatocytes
2. Microsomal ethanoloxidizing system
(MEOS) – participates if blood alcohol
levels high
3. Catalase – use H2O2 as substrate
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Alcohol
• Acetaldehyde  many toxic effects  responsible

for some of the acute effects of alcohol and for
the development of oral cancers.
• Alcohol oxidation by ADH  reduction of NAD to

NADH  accumulation of fat in the liver and
lactic acidosis
• Metabolism of ethanol in the liver by CYP2E1 

reactive oxygen species  lipid peroxidation of
cell membranes
• Release of endotoxin by intestinal flora  release

of TNF & cytokines from Kupffer cells  hepatic
injury
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Alcohol
Acute Alcoholism
• Affects mainly CNS  depressant (first

affecting high brainstem reticular
formation)  stimulation and disordered
cortical, motor, and intellectual behavior
• Moderate intake  fatty change or

hepatic steatosis
• Gastric changes: acute gastritis and

ulceration
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Alcohol
Chronic Alcoholism
• Affects not only liver and stomach,

but virtually all other organs and
tissues as well
• Significant morbidity with shortened

life span
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Areas of
brain that
can be
damaged
in utero by
maternal
alcohol
consumpti
on
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Features of Fetal Alcohol Syndrome
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Babies diagnosed with Fetal Alcohol

Syndrome may have some but not all
of the following physiological
characteristics:
• Small birth weight

• Small head circumference
• Small, widely spaced eyes
• Flat midface
• Short, upturned nose
• Smooth, wide philtrum
• Thin upper lip
Note: Facial characteristics may not be

as apparent immediately after birth or
during adolescence or adulthood as
they are between the ages of two and
ten. Facial characteristics may not be
present at all if the mother did not
drink during the brief period that the
midface was forming around the 20th
day of pregnancy.
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Injury by Therapeutic Agents
Hormonal Replacement Therapy
• Most common type: estrogen +

progesterone
 Estrogen therapy alone used in
hysterectomized patients due to risk
of uterine cancer
• Used in postmenopausal women to
prevent or slow the progression of
osteoporosis and reduce likelihood of
M.I.
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• Increased risk of breast cancer (lobular

and ductallobular carcinomas) after
median time of 5 to 8 years
• Protective effect on development of AS

and coronary disease in women < 60 
depends on response of estrogen
receptors that regulate calcium
homeostasis in blood vessels
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• Increased risk of venous thrombo

embolism including deep vein
thrombosis, pulmonary embolism, and
stroke
 More pronounced during first two
years of treatment and in women
with risk factors (immobilization,
hypercoagulable states)
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Oral Contraceptives
• Synthetic estradiol and variable

amount of progestins  inhibit
ovulation or prevent implantation
• Present formulations with smaller

amounts of estrogen (~20 ug of ethinyl
estradiol)  fewer side effects
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Oral Contraceptives
• Threefold increased risk of venous

thrombosis and pulmonary thrombo
embolism  due to acute phase
response [inc. Creactive protein and
coagulation factors; decreased anti
coagulants (protein S and anti
thrombin III)]
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Oral Contraceptives
• Increased risk of myocardial infarction

in smoking women of all ages and in
nonsmoking women > 35 y/o
• Reduced incidence of endometrial and

ovarian cancers
• Increased risk of developing hepatic

adenoma
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Anabolic steroids
• Synthetic versions of testosterone
• 10 – 100 times higher than therapeutic

indications  inhibit production and
release of LH and FSH, and increases
amount of estrogens
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Acetaminophen
• Most commonly used analgesic in U.S.

 Cause of about 50% of cases of
acute liver failure
• Intentional overdosage (suicide) the

most common cause of toxicity
• 5% metabolized through activity of

CYP2E to NAPQ1
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Aspirin (Acetylsalicylic Acid)

• In adults, overdose is usually suicidal
• Source of salicylate poisoning is excessive use of

ointments containing oil of wintergreen (methyl
salicylate)
• Ingestion of 2 – 4 gm by children or 10 – 30 gm by
adults may be fatal
• Chronic toxicity: intake of 3 gm or more/day 

salicylism
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Drug Abuse
Cocaine (Crack)
• Extracted from leaves of coca plant 

prepared as watersoluble powder
(cocaine HCl)
• Snorted or dissolved in water and

injected SC or IV
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Cocaine HCl is the Crack cocaine is made in

final product exported the U.S. from several basic
from South America household products and
cocaine HCl.
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Drug Abuse
Cocaine (Crack)
Cardiovascular Effects:
• Most serious physical effect due to
acute action on CVS: tachycardia,
HPN, peripheral vasoconstriction
• Sympathomimetic effect  block re

uptake of epinephrine and NE while
stimulating presynaptic release of NE
 accumulation of epinephrine & NE
in synapses  excess stimulation
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Drug Abuse
Cocaine (Crack)
Cardiovascular Effects:
• Coronary artery vasoconstriction 

myocardial ischemia  M.I.
• Enhanced platelet aggregation and

thrombus formation
• Impaired ion transport in myocardium

 lethal arrhythmia
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Drug Abuse
Cocaine (Crack)
CNS Effects:
• Aberration of dopaminergic pathways

 hyperpyrexia
• Seizures
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Drug Abuse
Cocaine (Crack)
Effects on pregnancy
• Decreased blood flow to placenta 

fetal hypoxia and spontaneous
abortion
• Impaired fetal neurologic
development
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Drug Abuse
Heroin
• Opioid derived from poppy plant

• Closely related to morphine
• More harmful than cocaine
• Physical effects related to:
1. Pharmacologic action of the agent
2. Reactions to the cutting agents or
contaminants
3. Hypersensitivity reactions to the drug
or its adulterants
4. Diseases contracted due to use of
infected needles
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Drug Abuse
Heroin
Sudden death
• Related to overdose
• Death due to:
1. Respiratory depression
2. Arrhythmia and cardiac arrest
3. Severe pulmonary edema
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Drug Abuse
Heroin
Pulmonary injury
• Moderate to severe edema

• Septic embolism from endocarditis
• Lung abscess
• Opportunistic infections
• Foreign body granuloma from
adulterants
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Drug Abuse
Heroin
Infections
• Four sites most commonly

infected: skin and SC tissue, heart
valves, liver, and lungs
• S. aureus, viral hepatitis, fungi,
HIV
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Drug Abuse
Heroin
Skin
• Most frequent telltale sign of

addiction
• Acute changes: abscesses, cellulitis,
ulceration
• Chronic use: hyperpigmentation
over used veins, venous thrombosis
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Drug Abuse
Heroin
Kidneys
• Two forms most frequently

encountered:
1. Amyloidosis secondary to skin
infections
2. Focal glomerulosclerosis
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Drug Abuse
Amphetamines – Metamphetamine
• “speed” or “meth”
• Closely related to amphetamine but
with stronger CNS effects
• Acts by releasing dopamine in the brain
 inhibit presynaptic
neurotransmission at corticostriatal
synapses  slow down glutamate
release
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Drug Abuse
Amphetamines – MDMA
• “ecstasy”
• 3,4 methylenedioxymethamphetamine
• Increase serotonin release in the CNS +
impaired serotonin synthesis
• Decrease number of serotonergic axon
terminals in the striatum and the cortex
• Increase peripheral effects of dopamine
and adrenergic agents
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Drug Abuse
Marijuana (“pot”)
• Made from the leaves of Cannabis sativa

 tetrahydrocannabinol (THC)
• Potential use to treat nausea secondary
to cancer chemotherapy & pain
reduction in cases of chronic pain
• Endogenous cannabinoid system –
cannabinoid receptors CB1 and CB2
(endocannabinoids)  participate in
regulation of hypothalamicpituitary
adrenal axis  modulate control of appetite,
food intake, and energy balance, including
fertility and sexual behavior
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Thermal Injury
Thermal Burns
• Clinical significance of burn injury

depends on the following factors:
1. Depth of the burns
2. Percentage of body surface involved
3. Internal injuries due to inhalation of
hot and toxic fumes
4. Promptness and efficacy of treatment
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Thermal Injury
Superficial Burns
• Firstdegree
burns; confined
to epidermis
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Thermal Injury
Partialthickness
Burns
• Seconddegree
burns; includes
dermis
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Thermal Injury
Fullthickness Burns
• Thirddegree
burns; extend to
SC tissue and
may involve
muscle tissue
underneath
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Thermal Injury
Thermal Burns: Complications
3. Shock, sepsis, and respiratory insufficiency
• Greatest threats; burns > 20% of body

surface  rapid shift of body fluids into
interstitial compartments 
hypovolemic shock
• Development of hypermetabolic state

associated with excess heat loss and
increased need for nutritional support
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Thermal Injury
3. Shock, sepsis, and respiratory insufficiency
• Burn site ideal for growth of organisms

 P. aeruginosa (most common), S.
aureus, fungi, Candida
• Most common serious sequelae:

pneumonia or septic shock with renal
failure and/or ARDS
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Thermal Injury
3. Injury to airways and lungs
• Develop within 24 to 48 hours after the

burn
• May be the result of:

• Direct effect of heat on mouth, nose, and
upper airways
• Inhalation of heated air and noxious
gases in the smoke inflammation and
swelling  partial or complete airway
obstruction
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Thermal Injury
3. Development of hypertrophic scars
• Both at site of original burn and at

donor graft sites
• Injured nerve endings  release of

substance P  excess neuropeptides 
continuous angiogenesis  scar
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Thermal Injury
Hyperthermia – Heat cramps
• Results from loss of electrolytes via

sweating
• Cramping of voluntary muscles in

association with vigorous exercise 
HALLMARK
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Thermal Injury
Hyperthermia – Heat exhaustion
• Most common hyperthermic

syndrome
• Sudden onset with prostration and
collapse  due to failure of CVS to
compensate for hypovolemia
• Collapse brief and equilibrium
spontaneously reestablished
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Thermal Injury
Hyperthermia – Heat stroke
• Associated with high ambient temp.,

high humidity, and exertion
• Failure of thermoregulatory
mechanisms  no sweating, core
body temp. > 400C  multiorgan
dysfunction  rapidly fatal
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Thermal Injury
Hypothermia
• Prolonged exposure to low ambient

temperatures
• Body temperature of 900F  loss of

consciousness followed by
bradycardia and atrial fibrillation at
lower core temperatures
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Thermal Injury
Hypothermia Mechanisms
1. Direct effects
• Crystallization of intra and extra
cellular water  high salt
concentrations  physical
disruptions within cells
2. Indirect effects
• Result of circulatory changes
175
Thermal Injury
Hypothermia – Mechanisms
• Slowly developing chilling 

vasoconstriction and increased vascular
permeability  edema and hypoxia 
gangrene of extremities (e.g. “trench
foot”)
• Sudden, persistent chilling  vaso
constriction and increased blood
viscosity  ischemic injury and
degenerative changes of peripheral
nerves
176
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177
Radiation Injury
178
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NonIonizing Radiation Injury
Nonionizing radiation
• UV and infrared light, microwave

and sound waves
• Cause atoms in a molecule to move

or vibrate  not sufficient to
displace bound electrons from
atoms
179
NonIonizing Radiation Injury
• UV rays derived from sun 

increased incidence of SCCA, basal
cell carcinoma, and skin melanoma
• Degree of risk depends on:

• Type of UV ray
• Intensity of exposure
• Quantity of lightabsorbing
protective coat of melanin
180
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181
UVB sunlight is directly absorbed

by DNA resulting in single
strand breaks and the formation
182
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Ionizing Radiation Injury
Ionizing radiation
• Main sources:
1. Xrays
2. Gamma rays – electromagnetic
waves of very high frequency
3. Highenergy neutrons
4. Alpha particles (2 protons and 2
neutrons)
5. Beta particles – electrons
183
184
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Ionizing radiation
• Alpha particles  induce heavy

damage in a restricted area X-
• rays and gamma particles
 longer, deeper course with less
damage per unit of tissue
• With sufficient energy to remove
tightly bound electrons
 Cause collision of electrons with
other molecules  ionization
185
Major Determinant of Biologic Effects
Rate of delivery
• Divided doses  allow cells to repair
damage between exposures
Field size
• Small doses delivered to large fields
 lethal
• High doses delivered to small,
shielded fields  tolerable
186
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Cell proliferation
• Rapidly dividing cells (gonads, bone
marrow, lymphoid tissue, mucosa of
GIT) more vulnerable due to DNA
damage  mutations and
chromosomal abnormalities
• DNA damage in quiescent cells
compatible with survival if dose not
very high
187
Oxygen effects and hypoxia

• Production of reactive oxygen
species from radiolysis of water 
main mechanism of DNA damage
• Poorly vascularized tissues with low

oxygenation  less sensitive to
radiation therapy than nonhypoxic
tissues
188
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Vascular damage
• Damage to endothelial cells 

narrowing and occlusion of blood
vessel  impaired healing, fibrosis,
chronic ischemic atrophy
189
190
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191
Injury to arm of patient. Patient was

draped for procedure and physicians did
not realize that she had moved her arm so
that it was resting on the port of the Xray
tube during the procedure.
192
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193
194
97

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05/03/2019

Muhammad Farid Dimjati Lusno

Global Climate Change

• Human activity a major contributor

• Increases of carbon dioxide, methane, and

• Recent increases due to combustion of

Global Climate Change

• Present concentration of atmospheric

 Expected to increase to 500 – 1200

 Large scale deforestation a major

Global Climate Change

• Effects of global warming:

• Loss of reflective snow and ice  increased

Global Climate Change: Health Impacts

Global Climate Change: Health Impacts

Toxicity of Chemicals & Physical Agents

• Studies the distribution, effects, and

• Includes the study of the effects of

Toxicity of Chemicals & Physical Agents

1. The definition of poison is not

2. Xenobiotics are exogenous chemicals in the

Toxicity of Chemicals & Physical Agents

1. Chemicals may be excreted in urine,

2. Chemicals may act at the site of entry

Toxicity of Chemicals & Physical Agents

 Most solvents and drugs are lipophilic

 The most important catalyst in the

Cytochrome P450 enzyme system

• Primarily in endoplasmic reticulum

• Catalyze reactions that either:

• Production of reactive oxygen species

Cytochrome P450 enzyme system

• Great variation in activity of CYPs

Cytochrome P450 enzyme system

Environmental Pollution: Air Pollution

Outdoor Air Pollution

• Six major pollutants: sulfur dioxide,

• Lungs bear the brunt of adverse effects

Environmental Pollution: Air Pollution

Outdoor Air Pollution – Ozone

Environmental Pollution: Air Pollution

Outdoor Air Pollution – Ozone

Environmental Pollution: Air Pollution

Outdoor Air Pollution – Ozone

• Toxicity due to production of free radicals

• Other agents (e.g. Sulfur dioxide from

Environmental Pollution: Air Pollution

Outdoor Air Pollution – Particulate Matter

Environmental Pollution: Air Pollution

Outdoor Air Pollution – Carbon Monoxide

Environmental Pollution: Air Pollution

Outdoor Air Pollution – Carbon Monoxide

• Small, closed garage  lethal coma within

Environmental Pollution: Air Pollution

Outdoor Air Pollution – Carbon Monoxide

 Due to accidental exposure or suicide

Environmental Pollution: Air Pollution

Outdoor Air Pollution – Carbon Monoxide

 Slowly developing hypoxia  ischemic changes in

 Cessation of exposure  recovery but with

Environmental Pollution: Air Pollution

Indoor Air Pollution

Environmental Pollution: Metals