Download Delayed Radiation Injury

2015/11/11
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‫امراض‬
ENVIRONMENTAL PATHOLOGY
environment includes;
-outdoor
-indoor
-occupational
-personal, (tobacco, alcohol, drugs, diet).
environmental pathology deals with diagnosis, treatment, and prevention
of injuries and illnesses resulting from exposure to exogenous chemical
or physical agents, such exposure may occur in
-working place
-people may voluntarily expose themselves to these hazards
TOBACCO USE
Use of tobacco products, (cigarettes, cigars, pipes, and snuff) is
associated with more mortality and morbidity than any other personal,
environmental, or occupational exposure mainstream cigarette smoke
consists of:
-particulate phase
-gas phase
Contains more than 4000 constituents, including =====-43 carcinogens,
(Polycyclic aromatic hydrocarbons, polonium 210, 4-minobiphenyle,
2-naphthylamine, arsenic, nickel, N-Nitrosonornicotine cadmium,
chromium)
===-potential promoters (acetaldehyde and phenol)
===-irritants (NO2, CO)
Nicotine is an alkaloid that crosses the blood-brain barrier and
stimulates nicotine receptors in the brain
-responsible for acute pharmacologic effects, most likely mediated by
catecholamines
-responsible for tobacco addiction
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The inhaled agents in cigarette smoke
-may act directly on mucous membrane
-may be swallowed in saliva
-may be absorbed into blood stream
Most of the deaths attributable to cigarette smoking are due to
-lung cancer
-ischemic heart disease
-chronic obstructive lung disease
These dangers are dose related to cessation of smoking reduces the risks
of these disorders
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Smoking may contribute to cardiac arrest by:
-increasing platelets adhesion and aggregation
-triggering arrhythmia
-causing an imbalance between demand for O2 and supply to the
myocardium
The fetus is especially vulnerable to the consequences of maternal
smoking
-fetal hypoxia>low birth weight, prematurity
-increased incidence of spontaneous abortion
complications at the time of delivery
-premature rupture of membranes
-placenta previa
-abruptio placentae
Hazard of cigarette smoking at work place
-smokers have higher rates of accidental injuries
-smoke may act as a vector to transport other hazardous agents into the
lungs, such as radon gas in miners cigarette smoke is synergistic with
radon decay products in causing lung cancer
Tobacco exacerbates
-bronchitis
-asthma
-pneumoconiosis associated with exposure to silica, coal dust, cotton
dust, and welding fumes
-tobacco use also increases prevalence of peptic ulcers
Hazards associated with exposure to side-stream smoke (passive smoking,
or environmental tobacco smoke, ETS)
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-increase incidence of lung cancer and ischemic heart disease
-hazardous for infants and children
-maternal smoking increases the incidence of sudden infant death
syndrome
-young children suffer from increased incidence of respiratory and ear
infections and exacerbation of asthma
ALCOHOL ABUSE
Blood concentration of 80-100 mg/dl is the legal definition for driving
under the influence of alcohol in occasional drinkers, a blood alcohol
level of 200 mg/dl produces inebriation; with coma and death, and
respiratory arrest at 300-400 mg/dl habitual drinkers can tolerate blood
alcohol levels up to 700 mg/dl
chronic use results in psychological and physical dependence, genetic
factors may be involved
Metabolism of ethanol is directly responsible for most of its toxic effects
Effects of ethanol on various organs could also be attributed to specific
vitamin deficiency
Effects of ethanol on various organs
-nervous system
acute depression, and addiction
degeneration of > thiamine deficiency > chronic alcoholism
nerve cells, reactive gliosis,
and atrophy of the cerebellum and peripheral nerves (Wernicke syndrome
and Korsakoff psychosis)
-cardiovascular system
-cardiomyopathy
- hypertension
-acute gastritis--------gastrointestinal tract
-chronic users are vulnerable to acute and chronic pancreatitis
.liver
-fatty change
-acute alcoholic hepatitis
-cirrhosis
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skeletal muscles
-injure muscles
reproductive system, chronic effects -testicular atrophy and hypo-fertility
both in men and women
effect on pregnancy ----- spontaneous abortion
fetal alcohol syndrome
-growth defects
-developmental defects
ethanol and cancer
-association with cancers of, (oral cavity, pharynx, liver, esophagus,
possibly breast)
-acetaldehyde may act as a tumor promoter
-ethanol inhibits detoxification of chemical carcinogens
THERAPEUTIC DRUGS
adverse drug reaction is defined as a
toxic or undesired response to
a drug used at therapeutic doses to prevent, diagnose, or treat disease
predictive reactions are based on the known toxicity or mechanism of
action of a drug (dose related)
idiosyncratic reactions are rare and unpredictable, consequences may be
severe or even fatal
Oral Contraceptives
● their use is not associated with an increased risk of breast cancer.
● they decrease the risk of endometrial and ovarian cancers
● their use by HIV-infected women, increased risk of cervical cancer
● uncommon adverse effects, (venous thrombosis, cardiovascular disease
liver adenoma)
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Anabolic Steroids
● synthetic versions of testosterone used by athletes to improve
performance
● adverse effects, (dose 10-100 times of therapeutic dose)
-in adolescents, (stunted growth)
-in males, (acne, gynecomastia, testicular atrophy)
-in females, (growth of facial hair, menstrual disturbance)
-psychiatric problems
-premature heart attack
Hormone Replacement Therapy
estrogen therapy
risks include:
-increased risk of breast cancer if used for at least 5 years
-venous thrombosis
-cholecystitis
Aspirin
●overdose is accidental in children, and suicidal in adults
respiratory alkalosis>metabolic acidosis
●chronic aspirin toxicity in persons who take 3gm or more daily for years
●acute erosive gastritis>ulceration
●aspirin mixed with other analgesics > analgesic nephropathy
Outdoor Air Pollution
major sources
-combustion of fossil fuels
-mobile sources (motor vehicles)
-stationary sources (power plants factories, barbecues and fireplaces)
-photochemical reactions
-oxides of nitrogen and volatile hydrocarbons interact in the atmosphere
to produce ozone (O3) as a secondary pollutant
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-power plants, (sulfur oxide, particulates), aerosolized acid sulfates
contribute to acid rains
-waste incinerators, industry and smelters, (acid aerosols metals,
mercury vapors, organic compounds)
-lungs are the major targets of outdoor air pollution, especially vulnerable
are:
-Children
-asthmatics
-people with chronic lung or heart disease
major air pollutants
Ozone
major component of smog that accompanies summer heat waves .it
oxidizes polyunsaturated lipids to hydrogen peroxide and lipid aldehydes,
(irritants to mucus membranes)
Nitrogen Dioxide----dissolves in water in the respiratory airways
passages > nitric and nitrous acids > damage epithelium
Sulfur Dioxide
soluble in water> resp.airways irritation
Acid Aerosols
in the atmosphere sulfur and nitrogen dioxides are oxidized to sulfuric
and nitric acids respectively, which are dissolved in water droplets or
adsorbed to particulates, (both are irritants to the airways epithelium and
alter mucocilliary clearance)
Particulates
deposition and clearance of particulates inhaled into the lungs depend on
their size, (less than 0.1 micron in diameter, are more hazardous) adverse
effects are due to:
-systemic cytokine release
-increased blood viscosity
-autonomic changes associated with variable heart rates and arrhythmias
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Indoor Air Pollution
Carbon Monoxide
By product of burning of gasoline, oil, wood, and natural gas, and
tobacco
effects of CO indoor pollution:
-reduces exercise capacity
-aggravate myocardial ischemia
-causes headache, dizziness, loss of motor control, and coma
Nitrogen Dioxide
produced by gas stoves and kerosene space heaters
impairs lung defenses > infection
Wood smoke
complex mixture of nitrogen oxides, particulates, and polycyclic aromatic
hydrocarbons
respiratory infections in children
Formaldehyde
highly soluble, volatile chemical used in the manufacture of textiles,
pressed wood, furniture, and insulation causes acute irritation of the eyes
and upper respiratory tract and exacerbation of asthma
Radon a decay product of uranium, widely distributed in the soil causes
lung cancer in miners
Asbestos Fibers
non-friable and un-disturbed fibers have low indoor levels
Bioaerosols
Legionella pneumonia > pneumonia
allergens associated with pets, dust mites, cockroaches, fungi, and molds
can cause allergic rhinitis ,asthma
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RADIATION INJURY
forms of radiation
waves
1--long wavelengths, low frequency
2--short wave lengths, high frequency
particles
approximately 80% of radiation is derived from natural sources
-cosmic radiation
-ultraviolet light
-natural radioisotopes (radon gas)
remaining 20% is derived from manufactured sources
-instruments used in medicine
-consumer products that emit radio waves or microwaves
-nuclear power plants
non-ionizing radiations
have long wave lengths and low frequencies, (electric power, radio
waves, microwaves, infra- red and ultraviolet lights), cause vibration and
rotation of atoms in biological molecules
ionizing radiations
have short wave lengths and high frequency, (X-rays, gamma rays,
cosmic rays), can ionize biologic molecule and eject electrons
particulate radiation include, (electrons , protons , nutrons, mesons,
deuterons)
Ionizing Radiation
The dose is measured in several units,(roentgen, rad ,gray , rem , Sievert)
These measurements do not directly quantify energy transferred per unit
of tissue and therefore do not predict the biologic effects of radiation
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Factors influence the biologic effects of ionizing radiation
● physical properties and dose of radiation
● rate of radiation
● rapidly dividing Versus quiescent cells
● single dose V regional doses
● cells in G2 and M phases are most sensitive
● type of cell involved
● enhancement of damage by O2
cellular changes of radiation injury
1- Acute changes
-necrosis
-damage to DNA, if DNA damage is severe or cannot be repaired > cell
cycle arrest > apoptosis
2- Chronic changes
-fibrosis
-mutation > cancer after 10-20 years
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Clinical Manifestations Of Exposure To Ionizing Radiation depend on
-dose
-duration
-mode of exposure
Acute Whole-Body Exposure
4 syndromes are recognized
1-sub-clinical or prodromal syndrome (less than 200 rem) mild
nausea and vomiting ,lymphocytes less than 1500/ml survival is 100%
2-hematopoietic syndrome (200-600 rem)
intermittent nausea and vomiting, petechiae and hemorrhage , maximum
neutrophil and platelet depression in 2 weeks , lymphocytes less than
1000/ml .infections, patient may require bone marrow transplantation
3-gastro-Intestinal syndrome
(600- 1000 rem)
-nausea, vomiting, diarrhea ,hemorrhage
-infection
-severe neutrophil and platelet depression
-lymphocytes less than 500/ml
-death in 10-14 days
4-central nervous system syndrome (more than 1000rem)
-Intractable nausea and vomiting ,confusion, convulsions, coma in 15
min-3hrs
-lymphocytes absent
-death in 14-36hrs
Effects Of Radiation Therapy
external radiation is delivered to cancers at fractionated doses with
shielding of adjacent tissues , radiation when delivered to the chest or
abdomen > acute radiation sickness
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Patients treated with radiation may have:
-sterility
-secondary cancer
-delayed radiation injury
Delayed Radiation Injury
● arteries, fibrosis of wall>narrowing of lumen
● capillaries , thrombosis or ectatic
● heart, restrictive pericarditis, myocardial ischemia > fibrosis
● skin
-epidermis (desquamation>atrophy)
-dermis (dilated vessels, fibrosis)
-radiation dermatitis (impaired healing, increased susceptibility to
infection, ulceration)
-skin cancer, as long as 20 years later
● brain (focal necrosis and demyelination of the white matter)
● spinal cord, (transverse myelitis)
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● lungs
-acute lung injury
-delayed radiation pneumonia
-cancer as late complication
● breast
-diagnostic radiation during adolescence increases the incidence of
breast cancer after 15-20 years
Ovaries>follicles degenerate acutely.
● Urinary tract
-kidneys (hypertension, atrophy)
-urinary bladder (epithelial necrosis> submucosal fibrosis)
-tumors of kidneys and urinary bladder
● gastro-Intestinal tract
-esophagitis, gastritis, and entero-colitis
-delayed injuries, (ischemic necrosis, fibrosis, strictures)
●testes, (infertility)
●eyes, (cataract)
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Ultraviolet Radiation
● Divided into A, B, and C
Ozone in the atmosphere is protective agent against ultraviolet radiation
● Chlorofluorocarbons interacts with and depletes ozone (increases
incidence of skin cancer)
● some protection from the effects of UV light is afforded by window
glasses
● sun-blocks and sunscreens offer greater protection
effects of UV radiation
-premature aging of the skin
-skin cancer
● acute effects of UVA and UVB are short-lived and reversible,
(erythema, pigmentation)
● Tanning is due to
-increase in number of melanocytes
-elongation and extension of dendritic processes
-transfer of melanin to keratinocytes
Electromagnetic Fields
● increased incidence of childhood leukemia at very high exposure
● Occupational exposures at higher levels have not been associated with
an increased risk of cancer or neuro-degenerative disease
OBESITY
is a disease of caloric imbalance resulting from excess intake of calories
above their consumption by the body that lead to accumulation of adipose
tissue of sufficient magnitude to impair health
assessment of obesity
-body mass index (BMI)
obese if BMI is above 30kg/sq. m
overweight if BMI is in the range of 25-30
-body weight
-triceps skin-fold thickness
-mid-arm circumference
-ratio between waist hip circumferences
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types of obesity
-central (visceral), fat accumulation in trunk and abdominal cavity
-peripheral, diffuse fat accumulation in subcutaneous tissue
associated diseases with obesity
-type 2 diabetes
-dyslipidemias
-cardiovascular disease
-hypertension
-cancer
pathogenesis of obesity
-peripheral (afferent system), generate signals from various sites
□ fat cells (leptin, adiponectin)
□ stomach, ilium, colon (ghrelin, peptide)
□ pancreas (insulin)
-hypothalamic arcuate nucleus generates efferent signals
-efferent system, carries hypothalamic signals to control food intake and
energy expenditure
Leptin
synthesized by fat cells’ ,.stimulated when fat store is abundant,.
It regulates
-food intake
-energy expenditure
-pro-inflammatory cytokine
-hematopoiesis and lymphopoisis
leptin resistance rather than deficiency may be prevalent in obesity
Adiponectin called “fat burning molecule”
“guardian angel against obesity”
produced mainly by adipocytes ,directs fatty acids to muscle for their
oxidation
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General Consequences Of Obesity
obesity is the main driver for metabolic syndrome (visceral adiposity,
insulin resistant hypertriglyceridemia, low HDL cholesterol), syndromeassociated diseases include:
-type 2 diabetes
-coronary artery disease
-fatty liver disease
-cholelithiasis
-Pickwickian syndrome
-osteoarthritis
Obesity And cancer
about 4% of cancers in men and 7% in women are associated with
obesity, the risk of cancer is related to
-hyperinsulinemia
-insulin resistance
obesity and hyperinsulinemia have an effect on steroids that regulate cell
growth and differentiation in different tissues
in men BMI is more than 25 kg/sq.m is strongly correlated with
-adenocarcinoma of esophagus
-thyroid cancer
-colonic cancer
-renal cancer
.in women BMI of more than 25 kg/sq. m is strongly correlated with
-adenocarcinoma of esophagus
-endometrial cancer
-gall bladder cancer
-renal cancer
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DIET AND CANCER
● factors related to carcinogenesis content of exogenous carcinogens
(aflatoxin-hepatocellular carcinoma)
● endogenous synthesis of carcinogens from dietary components
(nitrosamines and nitrosamides-gastric carcinoma)
● lack of protective factors (vitamins C and E, β-carotenes, fibers, and
selenium)
End
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