Transcript Enviromental pathology 2a. 2006

DRUG ABUSE
• Drug abuse has been defined as “the use of
any substance in a manner that deviates from
the accepted medical, social or legal patterns
within a given society:
* CNS depressants –alcohol, diazepines
* CNS stimulants – cocaine, amphetamine
* Narcotics – morphine
* Hallucinogens – marijuana, lysergic acid
diethylamide (LSD)
HOW DO SUBSTANCES OF ABUSE
CAUSE DISEASE?
• Direct effect. Sympathomimetic effects
and may cause severe hypertension.
• Side effects from contaminants.
• Long term effects:
– e.g. Marijuana irritate the bronchi and
cause chronic inflammation.
COMMON COMPLICATIONS OF
INTRAVENOUS DRUG ABUSE
• Local infections at the site of injection.
• Systemic infections such as endocarditis and
AIDS.
• Viral hepatitis.
• Glomerulopathy.
• Narcotic lung.
Cocaine
• An alkaloid extracted from the leaves of the
coca plant.
• Very addictive.
• Acute cocaine toxicity:
– Sympathetic nervous system stimulation,
resulting in dilated pupils, vasoconstriction,
increased arterial pressure, tachycardia, lethal
arrythmias and myocardial infarction.
– Central nervous system:Cerebral infarction and
intracranial hemorrhage, hyperpyrexia, seizures.
– Rhabdomyolysis, which may lead to renal
failure.
Effect of cocaine
Cocaine
• Chronic cocaine use may result in:
– Perforation of the nasal septum in cocaine snorters.
– Decreased lung diffusing capacity in those who
inhale the smoke of cocaine.
– Rarely, the development of dilated cardiomyopathy.
– Effects on pregnancy and fetus: abruptio placenta,
premature labor, intrauterine growth retardation.
CONSEQUENCES OF COCAINE
OVERDOSE
• Cocaine has sympathomimetic effects and may induce
tachycardia, hypertension, profound sweating, agitation,
dilated pupils and hallucinations.
• Severe intoxication is accompanied by seizure, cardiac,
arrhythmia and hypertension, or respiratory arrest.
• Cardiac arrhythmia may cause sudden death.
• Hypertension may be complicated by cerebral bleeding.
Heroin
• Closely related to morphine.
• Derived from the poppy plant.
• It is sold diluted with an agent (often talc
or quinine)  dose unknown.
• Is usually self-administered intravenously
or subcutaneously.
Heroin: Complications
• Sudden death
usually related to overdose, due to profound respiratory
depression, arrhythmia and cardiac arrest, and severe
pulmonary edema.
• Pulmonary complications:
edema, septic embolisms, lung abscess, opportunistic
infections, and foreign body granulomas.
• Infectious complications:
skin, heart (endocarditis), viral hepatitis, AIDS.
• Kidney disease:
amyloidosis, focal glomerulosclerosis
• Heroin overdose will cause hypothermia,
bradycardia, hypotension and coma
Marijuana:
Complications
• Functional and organic CNS consequences: cognitive
and psychomotor impairment inability to judge
time, speed, and distance  automobile accidents.
• Laryngitis, pharyngitis, bronchitis, asthma-like
symptoms, increased tar inhalation.
• Increases heart rate and sometime increases blood
pressure.
• Chromosomal damage.
HEAVY METALS
POTENTIALLY TOXIC IN THE HUMAN ENVIRONMENT
• Lead – found in old house paint used up to the
1940s, is a source of poisoning in children who
eat it. Industrial contamination of waters next to
foundries and smelters. Car batteries contain
lead.
• Mercury – an industrial contaminant.
Contamination of waters with mercury caused
Minimata disease in Japan.
• Aluminum.
WHAT ARE THE SIGNS OF
LEAD POISONING?
• Chronic accumulation of lead in the body has
many consequences:
* Lead lines on the gums.
* Lead lines in the epiphyses of long bones.
* Anemia develops due to the inhibition of
hematopoiesis (basophilic stippling).
* Renal toxicity. Lead damages proximal
renal tubules causing aminoaciduria and
glycosuria. Diagnostic intranuclear
inclusions are seen in proximal renal
tubules.
WHAT ARE THE SIGNS OF LEAD
POISONING?
• Gastrointestinal colics.
• Lead encephalopathy:
– CNS cell necrosis and demyelination with
astrocytosis.
– Peripheral nerve demyelination.
• In children, lead poisoning retards
mental development.
LEAD POISONING
Slide 10.15
Injury by physical agents
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•
•
•
Mechanical trauma.
Thermal injury.
Electrical injury.
Injury induced by
Ionizing radiation.
MECHANICAL INJURY
DETERMINANTS OF MECHANICAL INJURY
• The effects of mechanical trauma
depend on the :
* Force and rate at which it is
transmitted.
* Nature of the object used to inflict
the injury.
* Transfer area of impact.
* Part of the body injured.
Mechanical trauma.
Abrasion: produced by rubbing or scrapping,
resulting in removal of superficial layer (may be
epidermis only).
Contusion (bruise) : produced by a blunt object,
characterized by damage to blood vessels and
accompanied by bleeding, hematoma formation.
Laceration: a tear or disruption of skin and
underlying soft tissues, or internal organs
tissue caused by application of force by a
blunt object (have jagged, irregular edges)
due to excessive lateral displacement or stretching of
tissues.
Mechanical trauma
Incision : a defect skin and underlying soft tissues,
or internal organs inflicted by a sharp instrument.
Puncture wound: caused by a long narrow
instrument, either penetrating or perforating.
Bullet wound : a penetrating wound caused by a
fast speed projectile.
Thermal Injury
1. Thermal burns
2. Hyperthermia
3. Hypothermia
Thermal Injury
Thermal burns , depends on the :
• Depth of burn.
1st degree: epidermis only, increased vascular permeability and
edema, accompanied by acute hyperemia of the skin.
2nd degree: epidermis and superficial dermis, show necrosis of
the epidermis and the formation of subepidermal bullae. The
dermis is spared, and the epithelium regenerates from the hair
follicles
3rd degree: epidermis, dermis, and skin appendages which shows
massive necrosis and exudation of fibrin.
• Percentage of body surface involved
>50% is grave and potentially fatal, >20% rapid shift into
interstitiumshock
Thermal Injury
•Inhalation of hot and toxic fumes (Cl, SO2, NH3(
mouth, nose, URT inflammation& swelling;
NO & plastic fume lead to pneumonitis.
• Prompt therapy, which should include fluid and
electrolyte management, elevate room temperature,
appropriate nutrition, and prevention or control of
wound infections ( pseudomonas aerogenosa, s.
aureus, …).
(
Thermal Injury
Cause of death
• Shock is early (hours)
• pneumonitis: 24-48 hrs.
• Infections may be the leading cause
of death in burned patients.
Thermal injury:
2-Hyperthermia
CAUSES OF SYSTEMIC HYPERTHERMIA:
• Increased heat production (e.g.,
increased metabolic rate, exercise,
shivering).
• Decreased heat loss (e.g. peripheral
vasoconstriction).
• Extreme environmental temperature.
PATHOGENESIS OF HYPERTHERMIA
• Classified as pyrogen induced or
unrelated to pyrogens.
• Endogenous pyrogen-mediated
hyperthermia.
• Hyperthermia that is not mediated by
pyrogens may result from excessive
external heat or heat generated by
metabolic processes.
TYPICAL FINDINGS IN HEAT SHOCK
• Heat shock develops upon exposure to extremely
high temperatures.
• Affects the very old and the very young.
• The skin is very hot and the body temperature
reaches 42.5°C.
• Those who die have DIC and show wide- spread
mucosal and skin hemorrhages.
• Focal necrosis of myocardial and skeletal muscle
cells and tubular necrosis of the kidneys.
• Plasma potassium is elevated due to the release of
intracellular potassium from necrotic cells.
Thermal injury:
2-Hyperthermia
HEAT SHOCK (Stroke):
High temperature and high humidity, Thermoregulation
fail, sweating ceases, and core body temperature rises.
Marked generalized peripheral vasodilatation with
peripheral pooling of blood, necrosis of muscles,
arrhythmia, DIC, … .
Thermal injury:
2-Hyperthermia
Elevated temperature:
– Heat cramps: due to loss of electrolytes via sweating,
voluntary muscles, vigorous exercise.
– Heat exhaustion: The most common, sudden with
prostration and collapse (brief), result from failure of
cardiovascular system to compensate for hypovolemia,
secondary to water depletion.
Thermal Injury:
3-hypothermia
Prolonged exposure to low temperature:
Total body:
homeless peoples and alcoholics
Local reactions:
• Direct: related to physical dislocations within the the cells
and high salt concentration due to water crystallization.
• Indirect: related to circulatory changes, vasoconstriction,
increased vascular permeability, and increased viscosity of
the blood: ---> hypoxia and infarction of the affected
tissue (e.g. gangrene of toes or feet).
CONSEQUENCES OF ACUTE
HYPOTHERMIA
• Lowered body temperature and cooling of
blood.
• Peripheral constriction.
• Tachycardia.
• Muscle shivering.
• With progressive cooling, all body
functions slow down, slower respiration and
heart rate, hypotension and mental
confusion.
CONSEQUENCES OF PROLONGED
HYPOTHERMIA IN SNOW BOUND
MOUNTAIN CLIMBERS
• Peripheral blood vessel constriction, paleness of the
skin.
• Decreased stroke volume.
• Decreased diuresis.
• Mental changes. When the body temperature
decreases to 32C, the exposed person becomes
apathetic, lethargic and is less willing to “fight”.
When the body temperature drops to 28°C, the
respiratory and heart rate decrease and coma
develops.
Gangrenous necrosis of fingers secondary to freezing
Injury produced by Ionizing Radiation
• Ionizing radiation is an important tool for
clinical diagnosis and treatment of some
tumors
• At the same time , it is a potent mutagen and
destroyer of cells
Types of Ionizing Radiation
• 1- Electromagnetic:
– x-ray
– gamma ray
• 2- High energy neutrons, and
charged particles (alpha, beta,
protons)
Terms used to express radiation dose
• Roentgen (R): a unit of x- or gamma irradiation
defined by the quantity of induced ionization in air
(measure of exposure)
• Radiation absorbed dose (rad) and grays(Gy)
units : express the energy absorbed by target tissue from
the gamma and x-ray(1 rad= 1cGy= absorption of 100
ergs of energy per gram of tissue.
• Curie (Ci): disintegrations per second of a
spontaneously disintegrating radioisotope.
Terms used to express radiation dose
• Linear energy transfer (LET): energy loss per unit
of distance as electron volts per micrometer. LET is
very high for alpha , less for beta (penetrate short
distance and interact with many molecules) and even
less for gamma and x-ray (long distance, less
interaction).
• Relative biologic effectiveness (RBE):
LET of irradiation/ LET of cobalt gamma ray or (megavolt xray)
RADIATION MEASURED
• Gray (Gy) is the unit measuring the
absorption of ionizing radiation in
tissues. It corresponds to 100 rads or
100 ergs per gram of tissue.
Effects of ionizing radiation on cells and tissues
• The primary target is the DNA (mostly during mitosis)
• Tissue with high rate of cell turnover (like bone marrow and
GI tract mucosa) are extremely vulnerable to radiation.
• Presence of different types of cells within one organ
– (vascular injury in CNS).
• Other factors:
– rate of dose delivery (fractional doses )
– capacity of cells to repair themselves .
– the effect of O2.
IONIZING RADIATION
• Two ways:
* Direct high energy injury of macromolecules (DNA, RNA, proteins).
* Indirectly by causing electrolysis of
water, leading to the formation of
oxygen free radicals.
Effects of ionizing radiation
Ionizing Radiation: Morphology
• Nuclear Changes: swelling and condensation and
clumping of chromatin, nuclear membrane break.
Giant cells with pleomorphic nuclei or more than one
nucleus.
At very high dose: nuclear pyknosis, or lysis as a marker
of cell death.
• Cytoplasmic changes: swelling, mitochondrial
abnormalities, degeneration of endoplasmic reticulum.
• Vascular changes: dilation, degenerative changes
including endothelial cell swelling, vacuolation,
necrosis, thrombosis. Later: edothelial proliferation and
collagenous hyalinization with thickining of the media.
• Comment: some of the cellular changes may simulate cancer changes.
ARE ALL HUMAN TISSUES EQUALLY
SENSITIVE TO IRRADIATION?
• Highly radiosensitive tissues include :
– organs composed of labile cells, such as bone
marrow, intestines, skin, tests.
• Moderately radiosensitive tissues include :
– organs composed of stable cells, such as liver,
kidneys, endocrine organs.
• Radioresistant tissues are found in organs
composed of permanent cells such as:
– adult neurons.
EFFECTS OF TOTAL BODY IRRADIATION
• The outcome depends on the total dose administered:
*
*
Less than 0.5 Gy – no consequences.
0.5 –2Gy –acute radiation syndome marked by fatigue, nause
and vomiting.
*
2-6 Gy – hematopoietic radiation syndrome marked by
suppression of the bone marrow. Leukopena and thrombocytopenia develop approximately 2 weeks after radiation and
predispose the patient to opportunistic infections. It has a 2050% mortality.
*
6-10 Gy – gastrointestinal radiation syndrome.
Diarrhea and fluid and electrolyte loss. Mortality is in the
range of 50-100%.
*
Over 10 Gy –cerebral radiation syndrome. Convulsions,
delirium and coma may develop within hours and are
accompanied by 100% mortality.
LATE EFFECTS OF IRRADIATION
• Atrophy
• Vascular changs
• Fibrosis
• Carcinogenic effects
• Teratogenic effect on the fetus.
WHICH ORGANS SHOW LATE
EFFECTS OF IRRADIATION?
• Skin changes.
• Lungs – interstitial fibrosis.
• Bone marrow – hypoplasia of all blood cell
precursors.
• Salivary glands – atrophy and fibrosis.
• Testes – loss of germ cells, tubular hyalinization and infertility.
• Soft tissue in many parts show arterial
changes.
BEST EXAMPLES OF RADIATIONINDUCED CANCER IN MEN
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Skin cancer
Leukemia and lymphoma
Thyroid cancer
Osteosarcoma
Lung cancer
ADVERSE EFFECTS OF EXPOSURE
TO THE SUN
• Acute effects depend on the duration of exposure but are
predictable.
* Short-lived erythema, edema and blisters.
* Pigmentation.
• Chronic effects are also dose-dependent but not so
predictable.
* Accelerated aging of skin with solar elastosis.
* Actinic keratosis.
* Basal cell and squamous carcinoma.
* Melanoma.
Ionizing
Radiation:
Effects on
Organ
System
Syndromes Associated With Various
Levels of Total Body Irradiation
Syndrome
Dose (rad) Clinical manifestations
Hematopoietic
200-500
Gastrointestinal 500-1000
Cerebral
>5000
Nausea and vomiting,
lymphopenia,
thrombocytopenia, neutropenia,
later anemia.
Diarrhea, hemorrhage,
emaciation, death within days.
Listlessness and drowsiness,
convulsions, coma, death
within hours.