Download Environment Pathology and Disease

Environment Pathology
and Disease
Bethy S Hernowo
Faculty Of Medicine Universitas
Padjadjaran
Environmental Disease
‫ ٭‬Diseases & lesions caused by
chemical or physical injuries
‫ ٭‬Environmental disease : common
‫ ٭‬ILO (International Labor
Organization) estimated : 1.1 million
people, work-relate
Sources of Exposure

Environmental
– Man-made
 Intentional (Hg, Minimata, Japan)
 Accidental
– methyl isocyanate, Bhopal, India
– radiation, Chernobyl
– Natural (H2S/CO/CO2, Cameroon)
Occupational (mining, dye,
chemical)
 Iatrogenic (drugs)
 Self-administered (substance
abuse, suicide)

Mechanisms of Toxicity
Corrosive, tissue destruction (acids, alkali)
– desiccation
– protein destruction
denaturation
hydrolysis
– fat saponification
 Inhibition of enzyme activity
cyanide: cytochrome oxidase

ABSORPTION and DISTRIBUTIONS of TOXICANTS
Environmental Pollution
Air pollution
1. Outdoor Air Pollution
1.1. Ozone
1.2. Nitrogen dioxide
1.3. Sulfur dioxide
1.4. Carbon monoxide
1.5. Lead
1.6 Particulates
Major Outdoor Air pollutants
Air
pollutants
Origin(s)
Ozone
Interactions of oxygen with
various pollutants such as
oxide of nitrogen, sulfur, &
hydrocarbons
Nitrogen
dioxide
Come, & wood
Sulfur
dioxide
Combustion of fossil fuel such
as coal, gasoline, & wood
Consequences
Is highly reactive & oxidizes
polyunsaturated lipids that
become irritants & induce
release of inflammatory
mediators affecting all airways
down to bronchoalveolar
junctions
Dissolves in secretions in
airways to form nitric & nitrous
acids, which irritate & damage
linings of airway
Yields sulfuric acid, bisulfites,
and sulfites, which irritate &
damage linings of airways;
together with nitric acid,
contributes to acid rain
Carbon
monoxide
Incomplete combustion of
gasoline, oil, wood, and
natural gas
Lead
Discussed in a subsequent
section
particulates
Great variety of finely
divided (and therefore
airborne) pollutants
ranging from relatively
innocuous plaster dust to
highly dangerous asbestos
dust
May include lead, ash,
hydrocarbon residues, and
other industrial and
nuclear wastes
Combines with
hemoglobin to displace
oxyhaemogloblin &
thus induce systemic
asphyxia
Major contributor to
smog & a major cause
of respiratory disease
Patterns Of Lung injury Related To Air
Pollution
Lung response
Pathogenic Mechanism(s)
Acute or chronic
inflammation (e.c. Chronic
bronchitis)
Emphysema
Asthma
Hypersensitivity pneumonia
Pneumoconiosis
Direct cell injury
Neoplasia
Enhanced proteolysis
Allergic or irritant effect
Immunologic injury
Fibrotic reactions caused by
cytokines released from
macrophages & other
recruited leucocytes
Mutagenic & promoting
effects
Air pollution
2. Indoor Air Pollution
2.1. Tobacco smoke
2.2. Carbon monoxide
2.3. Nitrogen dioxide
2.4. Wood Smoke
2.5. Formaldehyde
2.5. Radon
2.6. Asbestos fibers
2.7. Manufactured mineral fibers
2.8 Bioaerosol
Health Effects Of Indoor Air Pollutans
Toxic And carcinogenic Metals
Heavy Metal Toxic Agents
 Mercury
(HgCl2 , ATN; org Hg, CNS
function)
 Lead ( inhibits heme synthesis, CNS
function, kidneys, GI)
– 2-11% of children in US exceed 10
μg/dL
 Arsenic
 Iron
Industrial Exposures
Organ/System
Effect
Toxicant
Cadiovascular
Heart disease
Carbon,monoxide,lead,solvents,
cobalt,cadmium
Respiratory
Nasal cancer
Lung cancer
Isopropyl alcohol,wood dust
Radon,asbestos,silica,bis(Chloromethyl)ether,nickel,arsenic,
Chromium,mustard gas
Grain dust,coal dust,cadmium
Berylium,isocyanates
Silica,asbestos,cobalt
COPD
Hypersensitivity
Fibrosis
Nervous
Peripheral neuropathies
Ataxic gait
Central nervous depression
Cataracts
Solvents,acrylamide,methyl
Chloride,mercury,lead,arsenic,
DDT
Chlordane,toluen,acryllamide,
Mercury
Alcohols,ketones,aldehydes,
Solventsradiation
Ultraviolet
URINARY
Toxicity
REPRODUCTIVE
Male infertility
Female infertility
Teratogenesis
HEMATOPOIEIC
Leukemia
Mercury,lead,glycols ethers,
Solvents
Napthylamines,4aminobiphenyl,benzidine,
Rubber products
Lead,pthalate plasticizers
Cadmium,lead
Mercury,polychlorinated
Biphenyls
Benzene,radon,uranium
SKIN
Foloculitis and acneiform
Dermatosis
Cancer
Polychlorinated bipyhenyls,
Herbicides
Ultraviolet radiation
GASTROINTESTINAL
Liver angiosarcoma
Vinyl chloride
Bladder cancer
Pneumoconiosis
‫ ٭‬The non-neoplastic lung reaction to inhalation of
mineral dust
‫ ٭‬Agent : coal dust, silica, asbestos, beryllium
‫ ٭‬Coal Workers’ Pneumoconiosis (CWP)
Spectrum of lung finding in coal workers
1. Asymptomatic anthracosis
2. Simple Coal workers pneumoconiosis
3. Progressive massive fibrosis (PMF)
Mineral Dust –Induced Lung Disease
Pathogenesis of
Pneumoconiosis
Morphology
1.
2.
Pulmonary anthracosis
Inhaled carbon pigment is engulfed by alveolar
or interstitial macrophage, then accumulate in
connective tissue  linear streak & aggregates
pigment identify pulmonary lymphatic & mark
the pulmonary lymph node
Simple CWP
Characterized : coal macules & coal nodule.
coal macules consist : dust-laden macrophages.
The lesion scattered, but uppers lobes & upper
zones of the lower lobes more heavily involved
Morphology
3. Caplan syndrome
Coexistence of rheumatoid arthritis with
a pneumoconiosis  development
distinctive nodular develop fairly
rapidly
The nodular lesions  central necrosis
surrounded by palisading fibroblast,
palsma cells, macrophages containing
coal dust & collagen
The syndrome also occur in asbestosis &
silicosis
Clinical course CWP
1.
2.
3.
4.
CWP usually benign  produce little
decrement in lung function
Minority cases pulmonary
dysfunction, hypertension & cor
pulmonale
CWP  PMF (progressive massive
fibrosis) linked variety factors : coal
dust exposure level & total dust
burden
PMF  tendency to progress even
absence exposure
Silicosis
‫ ٭‬Caused by inhalation crystalline silica
‫ ٭‬Occupations associated development
silicosis : quarry mining, sandblasting,
drilling, tunneling, & stone cutting
‫ ٭‬Incidence : 1500 cases each year in US
‫ ٭‬Silica :
1. Crystalline : quartz, cristobalite,
tridymite ( most toxic and fibrogenic)
2. Amorphous forms (most commonly
implicated in silicosis)
Classification Silicosis
1.
2.
3.
4.
Acute silicosis : exposure very
high level of silica & develops
quickly
Chronic ( nodular ) silicosis:
exposure over prolonged periods 
Characteristic fibrotic nodules of
silicosis
Complicated ( conglomerate
silicosis)  result progression of
chronic silicosis
Other pulmonary disease : silicosis
Morphology
Gross : Characteristic nodule in early
stage: tiny, barely palpable, discrete,
pale-to-blackened, nodules in upper
zones
Microscopically : silicotics nodule
demonstrates concentrically
arranged hyalinized collagen fibers
surrounding an amorphous center.
Microscopically: Silicosis
Clinical course
≈ Chronic silicosis  detected routine
chest radiographs (asymptomatic)
≈ Radiographs : fine nodularity in the
upper zones  function : normal/
moderately affected
≈ Most patients do not develop
shortness of breath until late in the
course
≈ The disease  slow to kill
Asbestosis
» Asbestos  family of crystalline hydrated
silicates
» Occupotional exposure to asbestos, linked
to:
1. Parenchymal interstitial fibrosis
(asbestosis)
2. Bronchogenic carcinoma
3. Pleural effusions
4. Localized fibrous plaque, rarely diffuse
fibrous plaque
5. Malignant pleural & peritoneal
mesothelioma
6. Laryngeal carcinoma
Pathogenesis Asbestosis
‫ ٭‬Dictate : concentration, size, shape & solubility of
different forms asbestos
‫ ٭‬Two forms asbestos:
1. Serpentine (fiber is curly & flexible) : Chrysotile
2. Amphibole (fiber is straight, stiff,& brittle)  more
pathogenic
‫ ٭‬The greater pathogenicity amphiboles related:
1. Chrysotiles impacted respiratory  removed
mucociliary  trapped gradually leached from tissue
2.
Amphiboles  align themselvesairstream  deliver
deeper  penetrate epithelial cells  reach
interstitium
Morphology
Gross: diffuse pulmonary interstitial
fibrosis
Microscopically : Characteristic 
asbestos bodies : golden brown,
fusiform or beaded rods with a
translucent center. They consist of
asbestos fibers coated with an iron
containing proteinaceous material.
Pleural plaque : well-circumscribes
plaque of dense collagens
Asbestos Body
Clinical course
≈ Indistinguishable from other diffuse
interstitial lung disease
≈ Typically, progressively worsening
dyspnea appears 10-20 years after
exposure
≈ The disease may static or progress
to congestive heart failure, cor
pulmonale and death.
Tobacco Smoking
400,000 deaths/yr (21% of all deaths
in US)
 50 Million smokers in US
 Smoke composition

– carcinogens (polycyclic HC, bnaphthylamine, nitrosamines)

Irritants and toxins
– ammonia, formaldehyde, oxides of
nitrogen
CO
 Nicotine

Relative Disease Risks
Associated with Smoking
Lung Ca death
Mouth Ca
Larynx Ca
Esophogus Ca
CAD >35 yo
Cerebro VD >35 yo
COPD
Male
22
27
10
8
3
4
10
Female
12
6
18
10
2
5
10
Ill health effects of smoking partially
reversible
Tobacco smoke
Adverse
effects of
smoking
Injury By Chemical Agents
Mechanisms of chemical injury:
1. Dose
2. Requirement for metabolic conversion
3. Sites of absorption, accumulation, or
excretion
4. Individual variation
5. The capacity of the chemical to induce
an immune response
6. Unintentional transmission of infections
Injury by
Therapeutic
Agents
(adverse Drug
Reactions)
Exogenous Estrogens And Oral
Contraceptives
Exogenous Estrogens ( alone &
usually natural estrogen)
Adverse effects of estrogen therapy :
» Endometrial carcinoma
» Breat carcinoma
» Thromboembolism
» Cardiovascular disease
1.
2. Oral contraseptives
Adverse effects of oral contraseptives
( contain synthetic estrogens & always with
progestin)
1.Breast carcinoma 6.Hypertension
2.Endometrial cancer 7. Hepatic
adenoma
3.Cervical cancer
8. Gallbladder disease
4.Ovarian cancer
9. Cadiovascular
5.Thromboembolism
disease
Acetaminophen
≈ When taken very large doses 
hepatic necrosis
≈ The window therapeutic dose : 0,5
gr
≈ Toxic dose : 15-25 gr
≈ Toxicity begins : nausea, vomiting,
diarrhea, sometimes shock and
jaundice
≈ Serious overdose : liver failure,
renal and myocardial damage
Aspirin (Acetylsalicylic Acid)
≈ Overdose ( 2-4 gr) : accidental
ingestion of large number table 
young children
≈ Suicidal ( 10-30 gr)  adult
≈ Effects : at first : respiratory
alkalosis  metabolic acidosis
death
≈ Chronic : take > 3 gr daily 
headache, dizziness, tinnitus,
difficulty hearing, mental confusion,
nausea, vomiting and diarrhea
Injury by Non
therapeutic Toxic
Agents
1. Lead poisoning
2. Carbon monoxide
3. Alcohol and drug
abuse
Clinical And
Pathologic Features
Of Lead Poisoning
Lead Lines
Lead causes injury by its multiple
metabolic effects:
1.
2.
3.
4.
5.
High affinity for sulfhydryl groups &
interferes with enzymes
Competes with calcium
Interferes with membraneassociated enzymes
Interferes with nerve transmission
and brain
Membrane effects damage the
kidneys
Morphology
Major target of Lead toxicity : blood,
CNS, GIT and kidneys
1. Blood changes  characteristic 
result lead accumulation occur fairly
early.
2. Brain damage is prone to occur in
children
3. GIT : colic, extremely severe
4. Kidney : proximal tubular damage
with intranuclear lead inclusions.
Normal Kidney
Acute Tubular Necrosis
Carbon Monoxide
‫ ٭‬Nonirritating, colorless, tasteless, odorless 
imperfect oxidation of carboneceous materials 
continues to be cause accidental & suicidal death
‫ ٭‬CO kills by inducing CNS depression
‫ ٭‬CO act as a systemic asphyxiant 
carboxyhemoglobin incapable carrying oxygen
‫ ٭‬Acute Poisoning: generalized cherry-red color skin
& mucous membrane
‫ ٭‬chronic poisoning : evoke widespread ischemic
changes in the CNS
Classification Of Drugs Of Abuse
Class
Examples
Sedatives & hypnotics
CNS symphatomimetics or
stimulants
Alcohol, barbiturates
Cocaine, amphetamines
Ritalin, weight loss products
Opioids
Heroin, morphine, methadone
Cannabinoids
Marijuana, hashish
Hallucinogens or psychedelics
Lysergic acid diethylamide
(LSD),mescaline
Aerosol sprays,glues,toluene
Inhalants
Nonprescription drugs
Ingredients :Atrophine,
scopolamin, antihistamine, weak
analgesics
Alcohol And Drugs Of Abuse
1.
Ethanol
2.
Cocaine
3.
Heroin
4.
Marijuana
5.
Other Illicit drugs
Metabolism of Ethanol
Ethanol
Adverse effects of ethanol:
1. Acute alcoholism  effects mainly
CNS  induced hepatic & gastric
changes
2. Chronic alcoholism  morphologic
alterations  liver & stomach
Normal Liver
Fatty Change in Liver
Fatty Change in Liver
Cocaine
Manifestations of acute cocaine toxicity
1.
Sympathetic nervous system stimulation 
dilatated pupils, vasoconstriction
2.
Lethal arrhythmias & myocardial infarction
3.
Cerebral infarction & intracranial hemorrhage
4.
Rhabdomyolysis
5.
In pregnant women  spontaneous abortion
Manifestations of chronic toxicity
1.
Perforation nasal septum
2.
Decreased lung diffusing capacity
3.
Dilated cardiomyopathy
Effect of cocaine on
neurotransmitters
CNS Synapse
Sympathetic Neuron-target Cell
Interfere
Heroin
≈ Effects : euphoria, hallucinations, somnolence &
sedations
≈ Heroin  adversed physical effects, related to
1.
Pharmacologic action of the agent
2.
Reactions to the cutting agents/contaminations
3.
Hypersensitivity reactions
4.
Diseases contracted incident  use needle :
‫ ٭‬Sudden death
‫ ٭‬Pulmonary complication
‫ ٭‬Infectious complications
‫ ٭‬Cutaneous lesions
‫ ٭‬Kidney disease
Marijuana

1.
2.
3.
4.
Effects:
Distorts sensory perception &
impairs motor coordination
Lung  laryngitis, bronchitis,
cough, hoarseness  increased risk
for cancer
Increased heart rate and blood
pressure  angina
Induce chromosomal damage
Other Illicit Drugs
The variety of drug try by those
seeking  new experiences
 Range : various stimulants
(amphetamines) to depressants
(benzodiazepines) to hallucinogens
(ectasy)
 Dangerous combination : alcohol &
driving

Injury By physical Agents

1.
2.
3.
4.
5.
◊



Mechanical Trauma
Abrasion
Contusion
Laceration
Incised wound
Puncture wound
Thermal Injury
Thermal burns
Hyperthermia
Hypothermia
Injury By physical
Agents
Abrasion : A wound
produced by scraping or
rubbing
Contusion : A wound
produced by a blunt
object  damage
blood vessels &
extravasation
Injury By physical Agents
Laceration : A tear or disruptive stretching of
tissue  force by blunt object
Injury By physical Agents
Puncture wound : caused by a long narrow instrument 
Penetrating when the instruments pieces the tissue &
Perforating  when it traverses a tissue to also create an
exit wound
Thermal injury

Gross:
Full-thickness burn are white or
charred, dry and anesthetic, depending
on the depht, partial-thickness burns
are mottled with blisters & painful
◊ Microscopically:
Devitalized tissue  coagulative necrosis,
adjacent to vital tissue  accumulates
inflammatory cells & exudation
Hyperthermia
Heat cramps  loss of electrolytes
via sweating
 Heat exhaustion  onset sudden,
most common hyperthermic
syndrome  failure Cardiovascular
system to compensate for
hypovolemia
 Heat stroke  high ambient
temperatures & high humidity 
thermoregulatory mechanism fail

Hypothermia

1.
2.
Local reaction. Chilling or freezing
of cells & tissues causes injury in
two ways
Direct effects  mediated by
physical dislocations within cells,
high salt consentration
Indirect effects  exerted by
circulatory changed
Electrical Injury


1.
2.
Electrical injuries  death  arise
from low-voltage or high-power
lines or lighting
Two types of injuries
Burns
Ventricular fibrillation or cardiac &
respiratory center standstill
Injury
Produced
By
Ionizing
Radiation
Effects of ionizing radiation on DNA
Injury Produced
By Ionizing
Radiation
Overview of the major
morphologic consequences
of radiation injury