Minilectureenvironment Pathology and Disease

8/14/2019 Minilectureenvironment Pathology and Disease

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Environment Pathology

and Disease

Bethy S Hernowo

Faculty Of Medicine UniversitasPadjadjaran


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Environmental Disease

Diseases & lesions caused by

chemical or physical injuries

Environmental disease : common

ILO (International LaborOrganization) estimated : 1.1 millionpeople, work-relate


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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)


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Mechanisms of Toxicity

Corrosive, tissue destruction (acids, alkali)

desiccation

protein destruction

denaturation

hydrolysis

fat saponification

Inhibition of enzyme activity

cyanide: cytochrome oxidase


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ABSORPTION and DISTRIBUTIONS of TOXICANTS


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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


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Major Outdoor Air pollutants

Airpollutants

Origin(s) Consequences

Ozone

Nitrogendioxide

Sulfurdioxide

Interactions of oxygen withvarious pollutants such asoxide of nitrogen, sulfur, &hydrocarbons

Come, & wood

Combustion of fossil fuel suchas coal, gasoline, & wood

Is highly reactive & oxidizespolyunsaturated lipids thatbecome irritants & inducerelease of inflammatorymediators affecting all airways

down to bronchoalveolarjunctions

Dissolves in secretions inairways to form nitric & nitrousacids, which irritate & damagelinings of airway

Yields sulfuric acid, bisulfites,and sulfites, which irritate &damage linings of airways;together with nitric acid,

contributes to acid rain


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Carbonmonoxide

Lead

particulates

Incomplete combustion ofgasoline, oil, wood, andnatural gas

Discussed in a subsequentsection

Great variety of finelydivided (and thereforeairborne) pollutantsranging from relativelyinnocuous plaster dust tohighly dangerous asbestos

dustMay include lead, ash,hydrocarbon residues, andother industrial andnuclear wastes

Combines withhemoglobin to displaceoxyhaemogloblin &thus induce systemic

asphyxia

Major contributor tosmog & a major causeof respiratory disease


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Patterns Of Lung injury Related To Air

Pollution

Lung response Pathogenic Mechanism(s)

Acute or chronicinflammation (e.c. Chronicbronchitis)

EmphysemaAsthma

Hypersensitivity pneumonia

Pneumoconiosis

Neoplasia

Direct cell injury

Enhanced proteolysisAllergic or irritant effect

Immunologic injury

Fibrotic reactions caused by

cytokines released frommacrophages & otherrecruited leucocytes

Mutagenic & promoting

effects


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Air pollution2. Indoor Air Pollution

2.1. Tobacco smoke

2.2. Carbon monoxide

2.3. Nitrogen dioxide

2.4. Wood Smoke2.5. Formaldehyde

2.5. Radon

2.6. Asbestos fibers2.7. Manufactured mineral fibers

2.8 Bioaerosol


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Health Effects Of Indoor Air Pollutans


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Toxic And carcinogenic Metals


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Industrial ExposuresOrgan/System Effect Toxicant

Cadiovascular

Respiratory

Nervous

Heart disease

Nasal cancer

Lung cancer

COPDHypersensitivity

Fibrosis

Peripheral neuropathies

Ataxic gait

Central nervous depression

Cataracts

Carbon,monoxide,lead,solvents,

cobalt,cadmium

Isopropyl alcohol,wood dust

Radon,asbestos,silica,bis(Chloro-methyl)ether,nickel,arsenic,

Chromium,mustard gas

Grain dust,coal dust,cadmiumBerylium,isocyanates

Silica,asbestos,cobalt

Solvents,acrylamide,methyl

Chloride,mercury,lead,arsenic,

DDT

Chlordane,toluen,acryllamide,

Mercury

Alcohols,ketones,aldehydes,

Solventsradiation

Ultraviolet


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URINARY

REPRODUCTIVE

HEMATOPOIEIC

SKIN

GASTROINTESTINAL

Toxicity

Bladder cancer

Male infertility

Female infertility

Teratogenesis

Leukemia

Foloculitis and acneiform

Dermatosis

Cancer

Liver angiosarcoma

Mercury,lead,glycols ethers,

Solvents

Napthylamines,4-aminobiphenyl,benzidine,

Rubber productsLead,pthalate plasticizers

Cadmium,lead

Mercury,polychlorinated

Biphenyls

Benzene,radon,uranium

Polychlorinated bipyhenyls,

Herbicides

Ultraviolet radiation

Vinyl chloride


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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


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Mineral Dust

Induced Lung Disease

P th i f


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Pathogenesis of

Pneumoconiosis


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Morphology

3. Caplan syndromeCoexistence of rheumatoid arthritis witha pneumoconiosis developmentdistinctive nodulardevelop fairly

rapidly

The nodular lesions central necrosis

surrounded by palisading fibroblast,palsma cells, macrophages containingcoal dust & collagen

The syndrome also occur in asbestosis &

silicosis


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Clinical course CWP

1. CWP usually benign produce littledecrement in lung function

2. Minority cases pulmonary

dysfunction, hypertension & corpulmonale

3. CWP PMF (progressive massive

fibrosis) linked variety factors : coaldust exposure level & total dustburden

4. PMF tendency to progress even

absence exposure


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Silicosis

Caused by inhalation crystalline silicaOccupations associated developmentsilicosis : quarry mining, sandblasting,drilling, tunneling, & stone cutting

Incidence : 1500 cases each year in USSilica :

1. Crystalline: quartz, cristobalite,tridymite ( most toxic and fibrogenic)

2. Amorphous forms(most commonlyimplicated in silicosis)


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Classification Silicosis

1. Acute silicosis : exposure veryhigh level of silica & developsquickly

2.

Chronic ( nodular ) silicosis:exposure over prolonged periods Characteristic fibrotic nodules ofsilicosis

3. Complicated ( conglomeratesilicosis) result progression ofchronic silicosis

4. Other pulmonary disease : silicosis


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Morphology

Gross : Characteristic nodule in earlystage: tiny, barely palpable, discrete,pale-to-blackened, nodules in upper

zones

Microscopically : silicotics noduledemonstrates concentrically

arranged hyalinized collagen fiberssurrounding an amorphous center.


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Microscopically: Silicosis


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Clinical course

Chronic silicosis detected routine

chest radiographs (asymptomatic)

Radiographs : fine nodularity in theupper zones function : normal/

moderately affected

Most patients do not develop

shortness of breath until late in thecourse

The disease slow to kill


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Asbestosis

Asbestos family of crystalline hydratedsilicates

Occupotional exposure to asbestos, linkedto:

1. Parenchymal interstitial fibrosis

(asbestosis)2. Bronchogenic carcinoma3. Pleural effusions4. Localized fibrous plaque, rarely diffuse

fibrous plaque5. Malignant pleural & peritoneal

mesothelioma6. Laryngeal carcinoma


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Pathogenesis AsbestosisDictate : concentration, size, shape & solubility of

different forms asbestosTwo forms asbestos:

1. Serpentine (fiber is curly & flexible) : Chrysotile2. Amphibole (fiber is straight, stiff,& brittle) more

pathogenicThe greater pathogenicity amphiboles related:

1. Chrysotiles impacted respiratory removedmucociliary trapped gradually leached from tissue

2. Amphiboles align themselvesairstream deliverdeeper penetrate epithelial cells reach

interstitium


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Morphology

Gross: diffuse pulmonary interstitialfibrosis

Microscopically : Characteristic

asbestos bodies : golden brown,fusiform or beaded rods with atranslucent center. They consist ofasbestos fibers coated with an ironcontaining proteinaceous material.

Pleural plaque : well-circumscribesplaque of dense collagens


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Asbestos Body


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Clinical course

Indistinguishable from other diffuseinterstitial lung disease

Typically, progressively worseningdyspnea appears 10-20 years afterexposure

The disease may static or progress

to congestive heart failure, corpulmonale and death.


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Tobacco Smoking

400,000 deaths/yr (21% of all deathsin US)

50 Million smokers in US

Smoke composition carcinogens (polycyclic HC, b-

naphthylamine, nitrosamines)

Irritants and toxins ammonia, formaldehyde, oxides ofnitrogen

CO

Nicotine

Relative Disease Risks


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Relative Disease Risks

Associated with Smoking

Male FemaleLung Ca death 22 12

Mouth Ca 27 6

Larynx Ca 10 18Esophogus Ca 8 10

CAD >35 yo 3 2

Cerebro VD >35 yo 4 5

COPD 10 10

Ill health effects of smoking partially

reversible


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Tobacco smoke

Adverse


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Adverse

effects of

smoking


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Injury By Chemical Agents

Mechanisms of chemical injury:

1. Dose

2. Requirement for metabolic conversion

3. Sites of absorption, accumulation, orexcretion

4. Individual variation

5. The capacity of the chemical to inducean immune response

6. Unintentional transmission of infections

Injury by


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Injury by

Therapeutic

Agents

(adverse Drug

Reactions)


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Exogenous Estrogens And Oral

Contraceptives

1. Exogenous Estrogens ( alone &usually natural estrogen)

Adverse effects of estrogen therapy :

Endometrial carcinoma

Breat carcinoma

Thromboembolism Cardiovascular disease


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2. Oral contraseptives

Adverse effects of oral contraseptives

( contain synthetic estrogens & always withprogestin)

1.Breast carcinoma 6.Hypertension2.Endometrial cancer 7. Hepatic

adenoma

3.Cervical cancer 8. Gallbladder disease4.Ovarian cancer 9. Cadiovascular

5.Thromboembolism disease


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Acetaminophen

When taken very large doses

hepatic necrosis

The window therapeutic dose : 0,5gr

Toxic dose : 15-25 gr

Toxicity begins : nausea, vomiting,diarrhea, sometimes shock andjaundice

Serious overdose : liver failure,renal and m ocardial dama e


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Aspirin (Acetylsalicylic Acid)

Overdose ( 2-4 gr) : accidentalingestion 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


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Injury by Non

therapeutic Toxic

Agents

1. Lead poisoning

2. Carbon monoxide

3. Alcohol and drug

abuse

Cli i l A d


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Clinical And

Pathologic Features

Of Lead Poisoning


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Lead causes injury by its multiple

metabolic effects:

1. High affinity for sulfhydryl groups &interferes with enzymes

2. Competes with calcium

3. Interferes with membrane-associated enzymes

4. Interferes with nerve transmissionand brain

5. Membrane effects damage thekidneys


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Normal Kidney


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Acute Tubular Necrosis


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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 asphyxiantcarboxyhemoglobin 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


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Classification Of Drugs Of Abuse

Class Examples

Sedatives & hypnotics

CNS symphatomimetics orstimulants

Opioids

Cannabinoids

Hallucinogens or psychedelics

Inhalants

Nonprescription drugs

Alcohol, barbiturates

Cocaine, amphetamines

Ritalin, weight loss products

Heroin, morphine, methadone

Marijuana, hashish

Lysergic acid diethylamide(LSD),mescaline

Aerosol sprays,glues,toluene

Ingredients :Atrophine,scopolamin, antihistamine, weakanalgesics


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Alcohol And Drugs Of Abuse

1. Ethanol

2. Cocaine

3. Heroin

4. Marijuana

5. Other Illicit drugs


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Ethanol

Adverse effects of ethanol:

1. Acute alcoholism effects mainlyCNS induced hepatic & gastric

changes

2. Chronic alcoholism morphologicalterations liver & stomach


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Normal Liver


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Fatty Change in Liver

F Ch i Li


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Fatty Change in Liver

C i


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CocaineManifestations of acute cocaine toxicity

1. Sympathetic nervous system stimulation dilatated pupils, vasoconstriction

2. Lethal arrhythmias & myocardial infarction

3. Cerebral infarction & intracranial hemorrhage

4. Rhabdomyolysis5. In pregnant women spontaneous abortion

Manifestations of chronic toxicity

1. Perforation nasal septum

2. Decreased lung diffusing capacity3. Dilated cardiomyopathy

Effect of cocaine on


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Effect of cocaine on

neurotransmitters

CNS SynapseSympathetic Neuron-target Cell

Interfere

Heroin


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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


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Marijuana

Effects:

1. Distorts sensory perception &impairs motor coordination

2. Lung laryngitis, bronchitis,cough, hoarseness increased risk

for cancer

3. Increased heart rate and bloodpressure angina

4. Induce chromosomal damage


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Other Illicit Drugs

The variety of drug try by thoseseeking new experiences

Range : various stimulants

(amphetamines) to depressants(benzodiazepines) to hallucinogens(ectasy)

Dangerous combination : alcohol &driving


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Injury By physical Agents

Mechanical Trauma1. Abrasion2. Contusion3. Laceration4. Incised wound5. Puncture wound Thermal Injury

Thermal burns Hyperthermia Hypothermia

Injury By physical


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Injury By physical

Agents

Abrasion: A wound

produced by scraping or

rubbing

Contusion: A wound

produced by a blunt

objectdamage

blood vessels &

extravasation


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Injury By physical Agents

Puncture wound : caused by a long narrow instrument

Penetratingwhen the instruments pieces the tissue &

Perforatingwhen it traverses a tissue to also create an

exit wound


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Thermal injury

Gross:Full-thickness burn are white orcharred, dry and anesthetic, dependingon the depht, partial-thickness burnsare mottled with blisters & painful

Microscopically:

Devitalized tissue coagulative necrosis,adjacent to vital tissue accumulatesinflammatory cells & exudation


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Hyperthermia

Heat cramps loss of electrolytesvia sweating

Heat exhaustion onset sudden,

most common hyperthermicsyndrome failure Cardiovascularsystem to compensate forhypovolemia

Heat stroke high ambienttemperatures & high humidity thermoregulatory mechanism fail


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Hypothermia

Local reaction. Chilling or freezingof cells & tissues causes injury intwo ways

1. Direct effects mediated byphysical dislocations within cells,high salt consentration

2. Indirect effects exerted bycirculatory changed


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Electrical Injury

Electrical injuries death arisefrom low-voltage or high-powerlines or lighting

Two types of injuries

1. Burns

2. Ventricular fibrillation or cardiac &respiratory center standstill

Injury


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Injury

Produced

ByIonizing

Radiation

Effects of ionizing radiation on DNA

Injury Produced


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j yBy Ionizing

Radiation

Overview of the majormorphologic consequences

of radiation injury


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