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ENVIRONMENTAL

PATHOLOGY
Chemical and Physical Agents
Nutrition
dr. Al Munawir, M.Kes., Ph.D.
Laboratorium Patologi Anatomi
Fakultas Kedokteran
Universitas Jember

Environmental Pathology
Magnitude of the Problem in
US

600,000 cancer cases/year related to


chemical carcinogens (est)
400,000 deaths related to smoking
Reported Chemical Exposures
2.4 million reported chemical exp/yr
(2005)
80% accidental
Children <6 year old, account for 50%
1261 fatalities, 50% suicides

US Government Agencies
Regulate Environmental
Hazards

Environmental Protection Agency


Food and Drug Administration
Occupational Safety and Health
Administration
Consumer Products Safety
Commission

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

Mechanisms of Toxicity
Corrosive, tissue destruction (acids, alkali)
desiccation
protein destruction
denaturation
hydrolysis
fat saponification
Inhibition of enzyme activity
cyanide: cytochrome oxidase

Cyanide Poisoning

Mechanisms of Toxicity
Alternate metabolic pathways
ethanol: NAD/NADH

Disturbances of homeostasis
steroids: immune system
aspirin: acidosis

Mutagenesis
Carcinogenesis

Clinical Findings
Symptoms-patient complaints
Signs-what you observe
Clinicopathologic correlation
related to mechanism and tissue
localization

Acute vs chronic-the signs and


symptoms may differ

Lung Injury Related to Air


Pollution
Acute and chronic inflammation
direct cell injury

Emphysema-enhanced proteolysis
Asthma-allergic or irritant effect
Hypersensitivity pneumonitis
immunologic injury related to organic
dusts

Pneumoconiosis-cytokines
Neoplasia
mutagenic/promoting effects

Main Constituents of Smog


SO2
respiratory irritant (acid rain)
NO2*, NO
respiratory irritant (xs O2)
CO carboxyhemoglobin (
O 2)
O3* respiratory irritant
Pb binds sulfhydryl groups
*Oxidant pollutants
Mostly produced by combustion of fossil fuels

Inhalation Toxins Related to


Mining and Similar Occupations
Pneumoconiosis, characterized by
cytokine-mediated, progressive fibrotic
scarring
coal dust (anthracosis)
silica (silicosis)
asbestos (asbestosis), Ca/Mg silicate
pleural plaques, mesothelioma,
bronchogenic ca

beryllium (berylliosis)
Macrophages produce cytokines
Size matters-0.5 to 5

Normal Lung

Pulmonary Fibrosis

Inhalation Toxins Related to


Farming
Organic dusts (hypersensitivity
pneumonitis)
moldy hay (Farmers Lung)
bird droppings (bird breeders lung)
Pesticides
organophosphate (acetycholine
esterase inhibitors)
organochlorine (DDT, chlordane)
Herbicides (paraquat, diquat, dioxin)
Fertilizer (ammonia)

Tobacco Smoking
400,000 deaths/yr (21% of all deaths in
US)
50 Million smokers in US
Smoke composition
carcinogens (polycyclic HC, -naphthylamine,
nitrosamines)

Irritants and toxins


ammonia, formaldehyde, oxides of nitrogen

CO
Nicotine

Relative Disease Risks


Associated with Smoking
Male
Female
Lung Ca death
22
Mouth Ca 27
6
Larynx Ca
10
Esophogus Ca 8
10
CAD >35 yo
3
2
Cerebro VD >35 yo
COPD
10 10

12
18
4

Ill health effects of smoking partially reversible

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 g/dL

Arsenic
Iron

Lead Lines

Basophilic Stippling

Normal Kidney

Acute Tubular Necrosis

Organic Alcohols
Ethanol
1/3 of Americans characterized as
heavy drinkers
CNS depressant
legally intoxicated >100 mg/dL
Nearly 50% of fatal MVA

Methanol (toxic metabolites inhibit


hexokinase, may cause blindness)
Ethylene glycol (antifreeze, ATN)

Fatty Change in Liver

Normal Liver

Fatty Change in Liver

Alcoholic Hepatitis

Mallory
Body

Alcoholic Cirrhosis

Alcoholic Cirrhosis

Bands of
Fibrosis
Regenerating
Nodules

Adverse Drug Events


Adverse Drug
Reactions
+
Therapeutic
Misadventures

Adverse Drug Events


3-6% of all medical admissions
160,000 deaths/yr
Shapiro et al. JAMA 1971; 216: 467-472.

Most common adverse event in hosp


pts
Leape et al. NEJM 1991;324: 377-384.

6.5 ADE/100 admissions, 1% fatal


Bates et al. JAMA 1995; 274: 29-34.

Major Patterns of ADRs


Blood dyscrasias (Chloramphenicol)
dose related or idiosyncratic
pan or line specific

Skin eruptions (Penicillin)


Hepatic reactions

fatty change (Tetracycline)


cholestasis (Chlorpromazine)
hepatitis (INH)
massive hepatic necrosis (Halothane)

Major Patterns of ADRs


Renal reactions
predictable (aminoglycosides)
hypersensitivity (sulfa)

Lung reactions
congestion
edema
hemorrhage
interstitial fibrosis

Major Patterns of ADRs


Cardiac reactions
arrhythmias
cardiomyopathy

CNS reactions
respiratory depression

Systemic reactions
anaphylaxis
vasculitis
hormonal effects (HRT, OC)

Syndromes Related to
Drugs of Abuse
Pulmonary complications (edema,
septic emboli, absess, opportunistic
infections)
Granulomas (adulterants)
Infectious complications
Kidney disease
Often related to diluents, cutting
agents, and needle sharing

Outdoor Air Pollution


Sumber utama: Commbution of fosil
fuels, photochemical reactions,
waste incinerators, etc.
Pollutants: Ozone, Nitrogen dioxide,
Sulfur dioxide, Acid aerosols,
Particulates.
Target: Skin, eye, and airway
irritations to Respiratory infections.

Indoor Air Pollution


Sumber utama: Ventilasi jelek.
Pollutant: CO, Nitrogen dioxide, Wood
smoke, Formaldehide, Radon,
Asbestos, mineral fiber, Bioaerosols.
Target: Skin, eye, and airway
irritations to Respiratory infections.

Industrial Exposures

Volatile organic compounds.


Polycyclic aromatic hydrocarbons.
Plastics, Rubber, and Polymers.
Metals.

Agricultural Hazards.
Organochlorine.
Organophosphate.
Carbamate.

Natural Toxins

Potent toxins and carcinogens.


Animal toxins.
Poisonous plants.
Amanita phalloides mushrooms.

A Case Report on Garlic adverse effects

A 60-year-old woman was presented with severe and sustained ches


che
after eating sliced raw garlic 12 hours previously.

This is the first report of garlic impaction and garlic-induced esophageal injury

Pathology Laboratory

ig. 1-4. Morphological changes of INT-40


cells observed at 24 hr after exposure.

A and C no change
B elongation, rounded cell (light microscope); apoptotic-frag
multinuclei and cells with chromatin condensation.

Pathology Laboratory

ig. 1-5. Cycle cell analysis of Fresh Garli


Extract treated on INT-407 Intestinal
Epithelial Cells.

Pathology Laboratory

abel 1-1. Cycle cell analysis of Fresh Garl


Extract treated on INT-407 Intestinal
Epithelial Cells.

Exposure(20minute)

Cyclecell

Vehiclealone
(PBS)

FGE100
g/mL

FGE300
g/mL

BGE300
g/mL

Hypodiploid

21

143*

62*

21

G1

627

435*

223*

668

133

93

104

113

G2,M

234

345*

626*

214

Increasing percentage cell with hypodiploid----- Apoptosis


Decreasing G1 and increasing G2, M-------Cycle Arrest

Pathology Laboratory

Fig. 1-6. Pretreatment of NAC protects


INT-407 Intestinal Epithelial Cells
from cytotoxicity.

Cytotoxicity of FGE completely blocked by NAC/ scavenger ROS


Its mediated by ROS generation

Pathology Laboratory

Fig.1-1.Cytotoxicityofgarlicextracts
(freshorboiled)

Freshgarlicextracthascytotoxiceffect,notboiledgarlic
Pathology Laboratory

Physical Injuries
Mechanical force
abrasion
laceration
incision
contusion

Gunshot wounds
entry wound
exit wound

Contusion/22 hours

Laceration with Marginal


Abrasion

Incision

Stab Wound

GSW/Contact

GSW/Close
Range/Stippling

GSW/Distant and
Contact

THERMAL INJURY
Cutaneous burns.
Hyperthermia (heat cramps, heat
exhaustion, heat stroke).
Hypothermia.

Electrical Injuries
Resistence of tissue (dry or wet skin).
Intensity.

Injuries Related to Changes in


Atmospheric Pressure

Hight-altitude illness.
Blast injury.
Air or gas embolism.
Decompression disease.

Radiation Injury
Direct (target) effect-radiation acts
directly on target molecules, such as
DNA
Indirect effect-free radical intermediary
Cell death, mutations, developmental
abnormalities
Tissues have differential radiosensitivity
Oxygen effect
Whole body radiation

FIGURE 8-22. Radiation-induced cancers.

Radiation Injury

Radiation Sensitivity of
Biological Tissue

Lymphocytes
Thrombocytes
Granulocytes
GI lining
Endothelial
cells
Neural tissue

Sensitivity
Cell Division
Most Sensitive Fastest

Least Sensitive Slowest

NUTRITION AND DISEASE


Food Safety: Additives and
contaminants
Nutritional deficiencies (energy,
essential amino acids and fatty acids,
vitamins and minerals).
Obesity.
Diet and systemic disease
Chemoprevention and cancer

Nutritional deficiencies

Ignorance and poverty.


Chronic alcoholism.
Acute and chronic illness (burns).
Self-imposed dietary restriction
(Anorexia nervosa, bulimia).

Protein-Energy Malnutrition
Marasmus.
Kwashiorkor.

FIGURE 8-23. Complications of kwashiorkor.

Nutritional deficiencies
Vitamin deficiency
Mineral deficiency

Vitamin Deficiency
Vitamin Function
A

Vision
Immune
system
Epithelium

Deficiency State

Diet, malabsorption
Night blindness,
xerophthalmia,
keratomalacia,
immune deficiency
Blood calcium Diet, malabsorption,
and phosphate inadequate sun, liver
and renal disease
Rickets,
osteomalacia

Vitamin Deficiency
Vitamin

Function

Deficiency State

E
Antioxidant Diet, malabsorption
tocopherols Free radical Neuromuscular
scavenger
deficits
K
Clotting
Malabsorption, loss
factors
of gut flora,
II, VII, IX, Coumadin therapy
X
bleeding

Vitamin Deficiency
Vitamin
Thiamine
(B1)
TPP

Function

Enzyme cofactor,
nerve
conduction
Riboflavine Enzyme co(B2)
factor
FMN, FAD
Niacin
Enzyme coNAD,
factor
NADP

Deficiency State
Diet, EtOH
Polyneuropathy,
cardiomyopathy,
Wernicke-Korsakoff
Diet, EtOH
Cheilosis, glossitis,
dermatitis (atrophy)
Diet, EtOH
Pellagra, dermitis,
diarrhaea, dementia

Vitamin Deficiency
Vitamin

Function

Deficiency State

Pyridoxine Enzyme co- Drugs (INH), EtOH


(B6)
factor
Similar to riboflavin
and niacin deficiency
C
HydroxylDiet, EtOH
ation of
Scurvey, weak
proteins
connective tissue
Antioxidant Bleeding, fractures,
gingival swelling,
peridontal disease, poor
wound healing

Obesity

Diet and systemic disease

Atherogenesis.
Hypertension.
Diverticulosis.
Colon cancer.
Calorie restriction.

Chemoprevention and cancer


Consume large quantity of fruit and
vegetables.

Pathology Laboratory