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: Complication

s• 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 METALSPOTENTIALLY 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.

Slide 10.15

LEAD POISONING

Injury by physical agents

• Mechanical trauma.

• Thermal injury.

• Electrical injury.

• Injury induced by Ionizing radiation.

MECHANICAL INJURYDETERMINANTS 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.

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.

Mechanical trauma

Thermal Injury

1. Thermal burns

2. Hyperthermia

3. Hypothermia

Thermal InjuryThermal 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

interstitiumshock

•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

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.

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

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.

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).

Thermal Injury: 3-hypothermia

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 32C, 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 x-

ray)

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 macro-

molecules (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 thrombocy- topenia develop approximately 2 weeks after radiation and predispose the patient to opportunistic infections. It has a 20- 50% 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 hyalini-

zation and infertility.• Soft tissue in many parts show arterial

changes.

BEST EXAMPLES OF RADIATION-INDUCED CANCER IN MEN

• 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 Nausea and vomiting, lymphopenia, thrombocytopenia, neutropenia, later anemia.

Gastrointestinal 500-1000 Diarrhea, hemorrhage, emaciation, death within days.

Cerebral >5000 Listlessness and drowsiness, convulsions, coma, death within hours.