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CHAPTER 2
ENVIRONMENTAL FACTORS
1. Environmental pathology and classification of environmental
factors
Environmental pathology encompasses а group of disease states that result from any of а variety of
environrnental factors.
Classification of environmental injury factors:
- physical factors
- chemical factors
- biological factors
- psychological factors
Factors of environment can lead to damages at various levels: submolecular, molecular, subcellular, cellular,
tissue, organ, organismic.
Physical injury factors. Physical injuries can produce systemic and local tissue lesions. In addition to injuries
produced by mechanical force, cell injuries from physical agents include thermal, electrical, and radiation
injuries.
Chemical injury factors. Exogenous toxins include alcohol, lead, carbon monoxide, and drugs. Examples of
such drugs are chemotherapeutic agents used for cancer and immunosuppressants used to prevent rejection in
organ transplant recipients. Some authors designate special group deficit injury. Deficit injury is state when a
deficit of water, oxygen, or nutrients occurs.
Physical or chemical agents and other mechanisms that are not recognized by the immune system induce
primarily a basic microcirculatory and phagocytic response (inflammation).
Biological injury factors:
- Infection: viruses, fungi, protozoa, and bacteria can cause injury or death.
- Helminths and the parasitic
- Arthropods and insects: spiders, scorpions, ticks
- Biological drugs: antitoxic serum, vaccines, blood for transfusion
Agents that are recognized by the immune system (eg, most infectious agents) induce a dual response
consisting of nonspecific inflammation as well as a specific immune response that enhances the effectiveness of
the basic inflammatory reaction.
Social factors are contacts of people, wars, dwelling, industrial premises, etc.
Environrnental factors is some degree of potential control by the individual or society.
2.
Physical injury
Mechanical Trauma
Cause of mechanical injury is mechanical force including surgery, trauma from motor vehicle accidents and
etc.
Mechanical forces may inflict a variety of forms of damage. The type of injury depends on the shape of the
colliding object, the amount of energy discharged at impact, and the tissues or organs that bear the impact.
The mechanical factor causes direct destruction of a cell membrane and endocellular organelle or/and
increase of permeability of cell membranes and endocellular organelle. After mechanical injury at site of
damage the inflammation develops.
The most frequent types of mechanical trauma are skin and soft tissues injuries. Soft-tissue injuries can
be superficial, involving mainly the skin, or deep, associated with visceral damage.
Fracture denotes a break or rupture of bone in which normal continuity is lost.
The injuries with visceral damage
Head injury may result in brain damage, with possible intracranial haemorrhage and skull fracture.
Abdominal injury may result in the following conditions: contusion, rupture of the spleen or liver,
sometimes with severe hemorrhage, rupture of the intestine, which саn result in peritonitis.
Thorax injury may result in the following conditions: rib fracture, possibly with penetration into palmonary
purenchyma or thoractc wall vessels; hemothorax; pneumothorax.
Causes of death at mechanical trauma may be hemorrhage into body cavities, fat embolism from bone
fractures, ruptured viscera, secondary infection, renal shutdown caused by acute tubular necrosis.
Thermal Injury
Both excess heat (at local action burn occeres, at sistemic one hyperthermia develops) and excess cold
(likewise, local action is frostbite and sistemic action is hypothermia) are important causes of injury.
Heat-Induced Injuries
Burns
Definition: Injury due to acute local hight temperature.
Pathogenesis: Cell injury occurs at exposure to temperatures exceeding 65°C (149° F), at which temperature
protein denaturation occurs. This causes coagulative necrosis, resulting in formation of toxic proteins (“burn
toxins”) that damage capillary structures and generate inflammation mediators. Local effects of this include an
exudative inflammatory reaction; systemic effects include burn shock with gastroduodenal stress ulcer
(generally a peptic stomach ulcer) and kidney failure.
Cutaneous burns are the most common form of localized hyperthermia.
The clinical significance of burns depends on the following important factors:

Depth of the burn

Percentage of body surface involved

Possible presence of internal injuries from inhalation of hot and toxic fumes

Promptness and efficacy of therapy, especially fluid and electrolyte management and prevention or
control of wound infections
A skin burn can be present in the following degrees of severity.
—First-degree burns (thermal erythema). The most minor burn causes erythema and edema in the epidermis,
with focal necrosis of epidermal cells. Ones are recognized by congestion and pain. Mild endothelial injury
produces vasodilation, increased vascular permeability, and slight edema. The injury heals completely.
—Second-degree burns (blistering) involve the full thickness of the epidermis and part of the dermis but
spare the adnexa of the skin (hair follicles, etc). Second-degree burn exhibits thermally induced disruption of
microcirculation with increased permeability. This leads to exudation of blood serum in an inflammatory
reaction, resulting in epithelial separation in the form of blisters (subepidermal blistering). Destruction of the
epithelial blisters leads to ulceration in which the dermis is intact. The injury can heal completely.
— In a third-degree burn, both the epidermis and dermis are necrotic. Third-degree burn (scabbing) exhibits
dark brown necrosis that can vary in depth and may be accompanied by areas of less severe injury. The dead
tissue is sloughed off, often leaving behind areas of ulceration. As the injury heals, it scars and contracts
severely, resulting in keloid formation and contracture
— Fourth-degree burns extend through muscle, bone, and internal tissues. Fourth-degree burn (charred
tissue) results from extremely high heat that chars tissue. The injury heals like a third-degree burn.
A more contemporary classification refers to full-thickness (third-degree) and partial thickness (first- and
second-degree) burns.
Healing of cutaneous burns is related to the extent of tissue destruction. First-degree burns, by definition,
have little if any cell loss, and healing requires only repair or replacement of injured endothelial cells. Seconddegree burns also heal without a scar because epidermal basal cells remain, and are a source of regenerating
cells for the epithelium. Third-degree burns, in which the entire thickness of the epidermis is destroyed, pose a
separate set of problems. If the skin appendages are spared, reepithelialization can arise from them. Initially,
islands of proliferation at the orifices of these glands grow and coalesce to cover the surface. Deeper burns that
destroy the skin appendages require new epidermis to be grafted. Burned skin that is not replaced by a graft
heals with dense scarring. Since this scar tissue lacks the elasticity of normal skin, contractures that limit
motion may eventually result. In severe burns, epithelial layers have been produced in vitro from cultured
keratinocytes derived from the patient's own surviving skin. This approach has permitted some severely injured
patients to survive, who previously would surely have died.
The surface area involved in a burn is a more important prognostic criterion than the degree of the burn.
Surface area is determined by the rule of nines. To determine the extent of a burn, the percentage of the total
body surface area (TBSA) affected is estimated. Despite continuous improvement in therapy, any burn
exceeding 50% of the total body surface, whether superficial or deep, is grave and potentially fatal.
Burns may be classified as major or minor, according to extent and depth. First-degree burns, although
painful, are classed as minor and have little systemic impact.
Major Burn. The immediate systemic consequence of a second-degree burn to more than 20% of the
body is extravasation of fluid, including high protein exudate, from the burn site.
Effects of a Major Burn, burn illness
Significant system disorders are called burn illness.
A major burn affects the metabolism and function of every cell in the body. All systems are compromised,
especially the cardiovascular system. Given the dependence of every organ on adequate blood flow, alteration
in cardiovascular function has wide-ranging implications for survival and recovery. Cellular changes also
occur.
The following stages in clinical current of burn illnesses are distinguished: burn shock, burn toxemia, burn
infection, burn exhaustion and outcome.
Burn shock. In the development of burn shock the important role belongs to the painful factor and excessive
nervous impulses order to the central nervous system.
Besides, immediately following a severe burn edema of the burned tissue and directly surrounding areas
occurs. Edema of the burned tissue results from a breakdown of the capillaries and from plasma fluid and
protein leaking into the interstitial space. The edema leads to increased tissue pressure, exacerbation of tissue
hypoxia, and worsening damage. Cytokines, prostaglandins, leukotrienes, and histamine all are released and
further increase capillary permeability. White blood cells are attracted to the area, especially neutrophils, which
produce free oxygen radicals and contribute to reperfusion injury.
After several more hours, edema spreads beyond the burned tissue, as the ability of distant capillaries to act
as barriers to diffusion is lost as well. This later edema of non-burned tissue appears to result from a transient
increase in capillary permeability to water and protein. The loss of capillary integrity is described as a loss of
capillary seal. The accumulation of fluid in the interstitial space throughout the body results in a significant
decrease in circulating blood volume, causing a fall in stroke volume and blood pressure. Pulse rate increases in
compensation. Irreversible shock may develop.
During the period of capillary leakage, blood viscosity increases and blood flow is sluggish. Individuals are
at increased risk of clot formation. With a weakly beating heart, blood accumulates in the lungs, causing
pulmonary congestion and increasing the risk of embolus formation. Decreased blood flow to the kidneys
causes renal hypoxia and a significant decrease in urine output. The renin-angiotensin system is stimulated,
resulting in increased salt and water retention. Because the capillaries do not contain the increased volume,
additional edema develops, further increasing the risk of pulmonary congestion and pneumonia. Hypoxia of the
gut causes injury to the mucus-producing cells, leading to gastric and duodenal ulcers. Within approximately 24
to 48 hours after a burn, the capillaries reseal and fluid is slowly reabsorbed back into the circulation. However,
the effects of the loss of seal remain, and the risk of morbidity and mortality continues to be high.
Burn toxemia. The disorder of nervous activity and hemodynamics are also promoted by intoxication due to
“burn toxins” (denatured protein and products of its hydrolysis), arriving from damaged tissues.
Burn infection. Severely burned patients who survive longer are at great risk of lethal surface infections and
sepsis. Even normal skin saprophytes may cause infection of charred tissue and pose another difficulty for
healing. Decreased immune function appears to result from the release of hormones, including but not limited
to cortisol. Cortisol is released with stress and is immunosuppressant at high concentrations. Immune function
is inhibited by a major burn. Loss of immune function, combined with loss of the barrier function of the skin,
puts an individual at high risk for infection.
Burn exhaustion Metabolic rate is significantly increased with a major burn. Hypermetabolism may result
from activation of the sympathetic nervous system and the stress response, as well as from attempts to balance
the heat loss that occurs when the insulatory function of the skin is lost. Healing of the burn also requires huge
amounts of energy. The temperature control center in the hypothalamus is affected by the response to a major
burn, leading to an increase in hypothalamic set-point. This increase may result from cytokines and other
peptides released during the widespread inflammatory response. The hypermetabolism, as well as the increase
in cortisol and epinephrine (hormones of the post-absorptive state) and changes in insulin sensitivity, leads to
tissue breakdown and protein and fat wasting. Protein breakdown contributes to severe muscle wasting.
Cellular Response to a Burn
In response to a major burn, cells outside the burned area may become permeable to electrolytes, causing
sodium and calcium to accumulate intracellularly, and magnesium and phosphate to leak out from cells. Water
diffuses into the cell and the cell swells. Injured cells burst, releasing potassium into the extracellular fluid.
These changes affect the membrane potential of all cells and can lead to cardiac dysrhythmias and alterations in
central nervous system function.
Inhalation Burns
Another important consideration in patients with burns is the degree of injury to the airways and lungs.
Inhalation injury is frequent in persons trapped in burning buildings and may result from the direct effect of
heat on the mouth, nose, and upper airways or from the inhalation of heated air and gases in the smoke. Watersoluble gases, such as chlorine, sulfur oxides, and ammonia, may react with water to form acids or alkalis,
particularly in the upper airways, and so produce inflammation and swelling, which may lead to partial or
complete airway obstruction. Lipid-soluble gases, such as nitrous oxide and products of burning plastics, are
more likely to reach deeper airways, producing pneumonitis. Unlike shock, which develops within hours,
pulmonary manifestations may not develop for 24 to 48 hours. If a patient survives the acute episode, acute
respiratory distress syndrome (ARDS), which itself may be fatal, may develop.
Complications

Any burn may become infected, causing further disability or death. Infections are the leading cause of
morbidity and mortality in patients who initially survive a major burn.

Sluggish blood flow may lead to the development of a blood clot, causing a cerebral vascular accident, a
myocardial infarct, or a pulmonary embolus.

Lung damage may occur from smoke inhalation or embolus formation. Pulmonary congestion may
result from left-heart failure or a myocardial infarct. Adult respiratory distress syndrome may develop. The
combination of smoke inhalation and a severe body burn increases mortality.

Burn shock may irreversibly damage the kidneys, leading to renal failure within the first week or two
after the burn. Renal failure also may develop as a result of renal hypoxia or rhabdomyolysis (myoglobin
obstruction of the kidney tubules secondary to widespread muscle necrosis).

Decreased blood flow to the gut may result in hypoxia of the mucus-producing cells, leading to peptic
ulcer.

Disseminated intravascular coagulation (DIC) may occur with widespread tissue destruction.

With a major or disfiguring burn, psychologic trauma may lead to depression, family breakup, and
thoughts of suicide. Psychological symptoms may occur any time after a burn. Symptoms may come and go
repeatedly over a lifetime as patients grieve and re-grieve over the losses encountered from the burn injuries.
Note: Death in the early phase after a burn injury results from hypovolemic shock and burn shock; death in the
late phase (after one week) results from uremia due to kidney damage.
Hyperthermia, Heat Injuries, Heat Stroke
Definition of hyperthermia: mismatch between heat production and heat loss resulting in a rising in body
temperature. Hyperthermia of an organism can lead to thermal injury (Heat Stroke)
Etiology. Elevated ambient temperature in combination with high humidity and/or inability to dissipate heat
as a result of muscular exertion (such as extreme sports), unsuitable clothing or obesity, or deficient physical
adaptability.
Pathogenesis.
The stages of the hyperthermia:
1. The stage of compensation, when the body temperature is within the normal.
2. The stage of decompensation, when the body temperature increases.
At the first stage compensatory - adaptive reactions act, in the second stage reserves of an organism are
exhausted.
Compensatory - adaptive reactions
Compensatory - adaptive reactions at hyperthermia order to mobilization of all ways of elimination of heat
from an organism:
1. Behavioural reactions (undressing, search of the shaded place and so on)
2. Increase sweating
3. Dilatation of vessels of skin
4. Increase of pulse and respiration rate
The thermoregulatory mechanisms of the organism are overtasked, especially when there is a lack of water
and at high ambient humidity. The body’s core temperature can no longer be kept at the (unchanged) set level
of 37° C.
The stage of decompensation develops, when physiologic cooling processes are overwhelmed and become
inactive;
On standing upright, heat-induced vasodilation causes some of the blood to pool in the legs, and the
extracellular volume is reduced by sweating. As a result, cardiac output put (CO) and blood pressure fall,
particularly because vasodilation in the skin reduces peripheral vascular resistance. Even at a core temperature
below 39 °C, weakness, dizziness, nausea, and loss of consciousness may occur as a consequence of reduced
blood pressure (heat collapse). Blood pressure will again rise on lying down and after taking fluids.
A much greater danger arises when the core temperature reaches 40.5° C, because the brain cannot tolerate
such temperatures. To protect itself against heat stroke the brain can temporarily be kept cooler than the rest
of the body because a rising core temperature causes profuse sweating of the head (even with dehydration),
especially the face. Blood that has been cooled in this way reaches the endocranial venous system and the sinus
cavernosus, where it lowers the temperature of the neighboring arteries. This would seem to be the only
explanation for the fact that a marathon runner in whom a transient rise in core temperature to 41.9 °C had been
measured did not suffer from heat stroke. If there is a prolonged rise in core temperature to between 40.5 and 43
°C, the thermoregulatory center in the midbrain fails and sweating ceases. Disorientation, apathy, and loss of
consciousness result (heat stroke). Cerebral edema with accompanying damage to the central nervous system
will, without rapid help, lead to death; children are especially at risk because their surface area to body mass
ratio is larger than adults’, and they produce less sweat. Treatment of heat stroke consist of bringing the person
into a cooler environment and/or submerging them into cool water. However, the body surface must not be
allowed to get too cold, because the resulting vasoconstriction would delay the reduction in core temperature.
Even successfully treated heat stroke may leave lasting damage in the thermoregulatory centers. This restricts
future tolerance to extreme temperatures.
Heat cramps occur with strenuous physical work in high ambient temperature (e.g., at a furnace) if only the
loss of water, but not of salt, is replaced.
Sun stroke must be distinguished from hyperthermia. It is caused by direct sun radiation head and neck and
causes nausea, dizziness, severe headache, cerebral hyperemia, and serous meningitis and may end fatally.
Contact or radiant heat may cause first degree, second degree, or third degree burns (reddening, blisters, or
necroses, respectively) to the skin. Frequent and intense exposure to the sun also increases the risk of
melanoma.
Cold-Induced Injuries
Hypothermia can result in systemic or focal injury.
Localized Cold Injury
Etiology: Local exposure of low temperature. The severity of local injury due to cold depends on the temperature, the
rate of chilling, and the duration of exposure. Two distinct conditions are recognized:
Immersion Foot (Trench Foot)
In localized hypothermia of these types, actual tissue freezing does not occur. Trench foot was recognized as a
common complication of trench warfare during World War I. Trench foot is the result of long, continued exposure of an
extremity to mud or water at cold but nonfreezing temperatures. Similar changes occur in any exposed part of the body.
The initial response of tissue to cold water is vasoconstriction, which if prolonged causes ischemic damage to muscle
and nerve. After several hours of continued immersion, vasomotor paralysis occurs, leading to fixed vasodilation and
damage to the microcirculation. The involved area becomes swollen and blue and is often extensively blistered.
Thrombosis ultimately occurs, often after several days' exposure, leading to gangrene.
Frostbite
Frostbite occurs more rapidly than trench foot and develops when a part of the body is exposed to freezing
temperatures. Where temperature continues to fall below freezing, water crystallizes out of tissue fluids. This increases
the pressure of the remaining tissue fluid, causing the cell to burst. Frostbite is not uncommon in temperate zones during
the winter months, when individuals are caught unprepared in snowstorms or snow-related accidents. Vasoconstriction,
dilation, and occlusion of vessels by agglutinated cells and thrombi occur, causing ischemic necrosis of the exposed area,
often within a few hours.
Generalized Hypothermia
Definition: mismatch between heat production and heat loss resulting in a drop in body temperature.
Etiology: generalized exposure of low temperature. While anyone may develop hypothermia when subjected
to prolonged outdoor exposure to cold weather, inside houses without adequate heating.
Immersion in water at 5–10°C can lead to hypothermia after only 10 minutes (depending on the amount of
“padding”). Wearing wet clothing in a strong wind and in an ambient temperature of 0°C can bring about
hypothermia in less than one hour.
Both the elderly (restricted thermoregulatory range) and infants (especially newborns), who have a relatively
high body surface area to mass ratio, low resting heat production, and a thin subcutaneous fat layer are
particularly at risk.
Heat production can be disrupted by lack of physical activity or by previous disorders that have decreased
the body’s defenses against cold.
Pathogenesis: Similarly to hyperthermia two stages are designeted in development of hypothermia: the
stages of compensation, when the temperature of a body is the normal, and the stage of decompensation, when
the temperature of a body decreases.
The stages of compensation
If there is a danger of the core temperature dropping, regulatory mechanism of heat maintenance results.
In the first stage compensatory - adaptive reactions act at two partway: in order to decreasing of heat losses
and to increasing of heat production
Reactions directed to decreasing of heat losses
1. Behavioural reactions. Its narrow limits are usually not overstepped, because the risk of cooling triggers
behavioral changes, depending on the underlying cause(s) (protection against wind, added clothing, leaving
swimming pool, etc.).
2. Reduction sweating.
3. Constriction of vessels of skin
Reactions directed to increasing of heat production are movement and shivering (muscle tremor). They
increase formation of primary heat due to dissociation of internic respiration and oxidive phosphorylation
reactions.
If those reaction don’t occur— either because it is not possible to escape the situation for physical reasons,
the danger is not realized, or there are metabolic, hormonal, or neurological abnormalities the decompensation
stage develops, i.e., the core temperature drops.
The stage of decompensation
Mild hypothermia (stage of excitement - 32 –35°C): maximal muscle tremor, resulting in a marked increase
in resting metabolic rate, all sources of glucose are utilized (hyperglycemia), and O 2 consumption is increased
up to sixfold. Tachycardia and vasoconstriction cause a rise in blood pressure; vasoconstriction causes pain.
The person is at first fully awake, later confused and even apathetic, and ultimately judgment becomes
impaired.
The moderate hypothermia (the stage of exhaustion, 32 –28°C): the sources of glucose become exhausted
(hypoglycemia); bradycardia, arrhythmia, and depressed breathing occur and the person begins to hallucinate
and to be behave perplexingly, soon losing consciousness and no longer feeling pain.
The severe hypothermia (the stage of paralysis < ca. 28°C): all biological processes slow down. This delays
the dissociation of oxygen from hemoglobin and increases the solubility of CO2 in plasma. The reduced
consumption of glucose in tissue leads to loss of consciousness and cardiac arrest. A drop in body temperature
below 25°C (77°F) causes heart and circulatory system failure with vascular thrombosis. This leads to organ
infarction and/or failure of the respiratory center.
The lower the temperature until cerebral blood flow ceases, the longer the brain will tolerate ate circulatory
arrest (30°C: 10–15 min; 18°C: 60 –90 min). This is why some persons have survived extreme hypothermia (<
20°C). The long time of circulatory arrest tolerated at low temperature is also of use in induced therapeutic
hypothermia (during open-heart surgery and preservation of organs for transplantation).
Long-term of successfully treated hypothermia includes heart failure, liver and kidney failure, abnormal
erythropoiesis, myocardial infarction, pancreatitis, and neurological disorders.
Electrical injury
Causes and conditions.
Electric current can only flow in a closed circuit that is characterized by a difference in potential or voltage
between two points in the circuit. Injury occurs when the human body becomes a part of this circuit. In most
cases, one part of the body is in contact with a live wire and another part with the ground.
The outcome of an electrical injury depends on

amperage and voltage,

the type of current (alternating or direct),

state of the tissue, the path within the body and the duration of contact.
Current flow (amperes) equals voltage (volts) divided by resistance (ohms). The severity of electrical injury
is directly related to the amount of current that flows through the body, which in turn is related directly to the
voltage difference and inversely to the electrical resistance. Severe electrical injuries are therefore more
common in countries that use a 220- to 240-volt domestic supply than those that use a 110-volt supply.
Electrical injuries caused by lightning and contact with high-voltage wires, which carry several thousand volts,
are very severe. Note that current flow also depends on the electrical resistance at the points of entry and exit—
eg, wet skin, which has a much lower resistance than dry skin, predisposes to more severe electrical injury.
Alternating current (AC) is more dangerous than direct current (DC) because it causes tetanic contraction of
muscles that may prevent the victim from letting go of the contact source.
The severity of tissue damage is dependent on the following factors: (1) The electrical resistance of the tissue. This is
inversely related to water content. Dry skin and bone have high resistance, whereas blood, nerve, and muscle are good
conductors. (2) The exact path taken by the current through the body and the organs in the pathway. For example, if earth
is the exit point, a current that enters the body in the leg and leaves through the foot will be much less harmful than one
which enters the hand because in the latter instance cardiac arrhythmias may develop as the current passes across the
heart. The duration of contact with the source of current.
Pathogenesis.
Basis of injuring action of current is disorder of movement of electrons in atoms (electrochemical action).
The passage of current also generates heat, the amount depending on the strength of the current, the electrical
resistance, and the duration of contact.
Injuries are of two types: sistemic and local action.
The current interferes with the function of tissues that depend on the generation of electrical action
potentials, eg, the respiratory and cardiac centers in the brain stem. Electrical current, especially alternating
current, disrupts nerve conduction and electrical impulses, particularly in heart and brain. Thus, this can lead to
severe cardiac arrhythmias, especially ventricular fibrillation, cardiorespiratory arrest, and violent muscle
spasms all may occur. These are immediate effects.
An important characteristic of alternating current, the type available in most homes, is that it induces tetanic
muscle spasm, so that when a live wire or switch is grasped, irreversible clutching is likely to occur, prolonging
the period of current flow. This results in a greater likelihood of developing extensive electrical burns and, in
some cases, spasm of the chest wall muscles, producing death from asphyxia. Currents generated from highvoltage sources cause similar damage; however, because of the large current flows generated, these are more
likely to produce paralysis of medullary centers and extensive burns. Lightning is a classic cause of highvoltage electrical injury.
Local reactions of the organism appear as result of transformation of electric energy in thermal and chemical
ones. The amount of tissue injury from standard current is generally not great, and there may be just a small
thermal injury. The skin has high electrical resistance and commonly shows thermal burns at the entry and exit
points of the current (lightning marks;). Current of very high voltage (eg, lightning) may produce enough heat
in skin to cause charring (flash burns) and to convert water into steam, causing soft tissues to explode and bones
to fracture. If current flow continues long enough, it generates enough heat at the site of entry and exit as well
as in internal organs. In bones as result of thermal fusion of the tissue and loss of calcium phosphate emptiness
are formed («a pearl beads») and fracture of the bones will be possible.
Radiation injury
Radiation is the transmission of energy through the emission of rays or waves. Radiation energy may be in
the visible range of light, or it may be higher or lower energy than visible light. High-energy radiation is called
ionizing radiation because it has the capability of knocking electrons off atoms or molecules, thereby ionizing
them. Low-energy radiation is called non-ionizing radiation because it cannot displace electrons off atoms or
molecules.
Sources of radiation.
A person can be exposed to ionizing radiation from a number of sources.
Daily low-level radiation from the sun is ever-present and (combined with ultraviolet rays) may be a factor
in the development of skin cancers and melanoma in individuals with prolonged exposure.
Direct environmental exposure to large doses (e.g., Hiroshima and Chernobyl) is associated with severe
effects on multiple organ systems.
Diagnostic and therapetic procedures expose a person to additional irradiation.
Mechanisms of injury
The following theories are proposed:
Direct Action
High-energy radiation directly alters or inactivates vital molecules in the cell, eg, deoxyribonucleic acid (DNA),
ribonucleic acid (RNA), and proteins.
Indirect Action radiation
Radiation causes ionization of intracellular water, producing high-energy particles, eg, H2O+ and H2O–. These
immediately dissociate and interact to form toxic free radicals such as H, OH, and H2O, which are highly unstable
particles that rapidly dissipate their energy by reacting with other molecules such as DNA, RNA, and proteins to cause
cell injury. The intermediate interactions between radiation and water occur in a few microseconds
Effects of Radiation Injury
DNA represents the main target of action of radiation. After high doses of radiation, extensive DNA injury leads to
cellular necrosis. With smaller doses, less severe abnormalities result that cause varying structural and functional
abnormalities of DNA—eg, the cell's ability to undergo normal mitosis may be affected. These DNA changes are
permanent and may be associated with the later development of cancer in radiation cells; leukemia (cancer of white blood
cells) developed in many Hiroshima survivors several years after the dropping of the atomic bomb
Variables influencing to the degree of injury:
1. Type of radiation
2. Quantity of radiation
3. Duration (Time frame)
4. Tissue properties
5. Cell type
Type of radiation
Electromagnetic waves, in the form of x-rays, for example, are far less destructive than the same dose in the
form of particles. Particles of higher mass, such as alpha particles, are more damaging than beta particles. Xrays, when uniformly distributed in а tissue field, may affect а11 cells but none seriously. Alpha particles,
which are heavier, would hit the tissues randomly but would be lethal to the subpopulation of cells that were
hit.
Quantity (dose) of radiation
The following terms are used to express radiation dose:

Roentgen (R) is a unit of x- or gamma radiation that ionizes a specific volume of air. Thus, it is a
measure of exposure.

Radiation absorbed dose (rad) and grays (Gy) are units that express the energy absorbed by target tissue
from gamma rays and x-rays. A rad or its equivalent, the centigray (cGy), is the dose that results in absorption
of 100 erg of energy per gram of tissue.

Rem is the dose of radiation that produces the biologic effect equivalent to 1 rad of x-rays or gamma
rays.

Curie (Ci) defines the disintegrations per second of a spontaneously disintegrating radionuclide
(radioisotope). One Ci is equal to 3.7 ×1010 disintegrations per second.
At total-body radiation the lethal range for humans begins at about 300 rads. Limited fields (e.g., those
treated in cancer therapy) are often given а high dose (еxceeding 4000 rads) without significant systemic effect.
Time frame. Not only the total dose of radiation absorbed, but also the dose rate influence the effects of
radiation.
A large dose of radiation received all at once has a far greater effect, particularly on normal tissues, than the
same total dose given as fractional doses over several incidents.
Therapeutic radiation is always split into fractions [commonly 200 rads (2 Gy) each] given over weeks to
months until the selected total dose is reached.
Cell type and tissue properties
Cells are affected in direct proportion to their normal rate of mitotic activity and reproduction and in inverse
proportion to their level of specialization.
High radiosensitivity. Rapid cell turnover is characteristic of the hair follicles, gastrointestinal tract, bone
marrow, lymphoid system, and germ cells.
Low radiosensitivity. The cells of certain organs (e.g., kidney, liver, pancreas) and tissues (e.g., mature
cartilage, muscle) rarely divide and are, thus, relatively less affected by radiation. Gradual loss of function may
result when such organs are within а therapeutic radiation field.
Intermediate radiosensitivity. Most other body tissues (e.g., connective tissue, vessels, urothelium) lie
between the two extremes just described.
Some tissues (e.g., subcutaneous adipose tissue and certain organs) offer far less resistance to radiation than
does the outer cutaneous shell.
Acute Radiation Syndrome
Total-Body Irradiation As little as 100 to 300 rad of radiant energy in total-body exposure delivered in one
dose may induce an "acute radiation syndrome." At 700 rad, death is certain without medical intervention.
Three often fatal acute radiation syndromes have been identified: (1) hematopoietic, (2) gastrointestinal, and (3)
cerebral-defined briefly in table1.
Tabl. 1. Clinical Features of the Acute Radiation Syndrome
Category Whole-Body
Symptoms
Prognosis
Dose (rem)
Subclini •<200
Mild nausea and vomiting; 100% survival
cal
Lymphocytes <1500/μL
Hematop 200–600
Intermittent nausea and Infections; May
oietic
vomiting;
Petechiae, require
bone
hemorrhage;
Maximum marrow
neutrophil
and platelet transplant
depression
in
2wk;
Lymphocytes <1000/ μL
Gastroin 600–1000
Nausea, vomiting, diarrhea; Shock and death
testinal
Hemorrhage and infection in 10–14 days
in
1–3
wk;
Severe even
with
neutrophil
and platelet replacement
depression;
Lymphocytes therapy
<500/μL
Central
••>1000
Intractable
nausea
and Death in 14–36
nervous
vomiting;
Confusion, hr
system
somnolence,
convulsion;
Coma in 15 min–3 hr
Lymphocytes absent
The acute symptoms are manifestations of the high sensitivity of rapidly proliferating tissues, such as the
lymphohematopoietic cells and gastrointestinal epithelium, to acute radiation-induced death of cell. Acute
radiation syndrome, thus, results in hair loss, nausea, vomiting, diarrhea, and susceptibility to bleeding and
infection. If the patient survives the acute radiation syndrome, sublethally injured cells may repair the radiation
damage, and the necrotic or apoptotic cells may be replaced by the progeny of more radioresistant stem cells.
The typical form of acute radiation syndrome has four phases:
I - primary general reaction,
II - visible clinical well-being (latent),
III - the expressed clinical phenomena (the height of illness),
IV - restoration
The phase of primary general reaction lasts 1-3 days and it is characterized by prevalence of nervous and
dispeptic disorders. The amount of neutrophilic leukocyte is increased because of redistribution of blood. The
amount of lymphocytes decreases (destruction of cells in interphase).
The phase of visible clinical well-being. Duration this phase is doze dependent and lasts from 10-15 days (at
major doze) to 4-5 weeks (at minor doze). It is characterized by gradual increasing of disorders in the most
radiosensitive bodies and tissues. State of patients is satisfactory. There is a gradual devastation of a bone
morrow and, hence, gradual reduction of amount of all uniform elements of blood
Phase of the expressed clinical phenomena. Clinical Features of acute radiation syndrome according to the
received doze are presented in the table. The picture of blood is characterized by a low level of blood cells of all
stream: leukocytes, erythrocytes, thrombocytes (cytopenia). The level and time of decrease of the blood cell to
minimum is doze depending. Young forms of cells are not present in blood.
Phase of restoration. The general state of patients improves. The amount of thrombocytes and leukocytes
increases up to a normal level. During rise of the level of leukocytes plenty of young forms is observed.
However the amount of erythrocytes continues to decrease and reaches a minimum level after 1 - 1,5 months.
The period of restoration lasts 3-6 months (sometimes 1-2 years).
Long-term effects of radiation.
Survivors of radiation exposure—even those who have been exposed to low levels—may demonstrate effects years
later. Detailed study of survivors of Hiroshima and Nagasaki has shown an increased incidence of cancer (particularly
leukemia), cataracts, infertility, and bone marrow aplasia. Exposure to radiation causes an increased number of genetic
abnormalities (mutations) that may be passed to subsequent generations. These changes appeared long after exposure, and
even the offspring of exposed individuals appear to be at increased risk for development of abnormalities.
Altitude-related Illnesses
High-altitude illness is rare, in large part because mountain climbers tend to acclimate before extreme
altitudes are achieved. However, there is an altitude limit beyond which human life cannot be sustained for
prolonged periods. Communities in the Andes succeed at 4000 to 4300 meters (13,124 to 14,108 ft). Inhabitants
adapt to the decreased pressure and availability of oxygen by developing elevated hematocrits and large
“barrel” chests with increased lung volume. Even those who live in this zone do not survive at elevations above
5500 to 6000 meters (18,045 to 19,686 ft). Prolonged stays at this altitude result in weight loss, difficulty in
sleeping, and lethargy, perhaps because of the redirection of cellular energy simply for survival. For example,
75% to 90% of the oxygen available at 6000 meters is used simply for the effort of inspiration.
The modifications induced by high altitude are related to decreased atmospheric pressure and consequent
decreased oxygen availability. Unlike sea level, where activity does not change oxygen saturation, physical
activity at these elevations leads to decreased partial pressure of arterial oxygen. At sea level, cardiac output
limits exercise; at high altitudes, the diffusing capacity of the lung for oxygen seems to be the determinant.
Acclimation to chronic hypoxia at high altitudes results in a reduced ventilatory drive. Acclimated persons
exhibit increases in: (1) capillaries per unit volume of brain, muscle, and myocardium; (2) myoglobin within
tissues; (3) mitochondria per cell; and (4) hematocrit. An increase in erythrocyte levels of 2,3-
diphosphoglycerate, which enhances oxygen delivery to tissues, occurs within hours, but polycythemia takes
months.
Some of the minor effects of high altitude are systemic edema, retinal hemorrhages, and flatulence. The
more serious nonfatal diseases are acute and chronic mountain sickness and high-altitude deterioration. Fatal
high-altitude pulmonary edema and high-altitude encephalopathy may ensue.

High-altitude systemic edema: This condition results from asymptomatic increases in vascular
permeability, particularly in hands, face, and feet, and most often at elevations over 3000 meters. It is reflected
only in weight gain; on return to lower altitude, diuresis causes the edema to disappear. This disorder may in
part reflect endothelial cell responses to hypoxia and is twice as common in women as in men.

High-altitude retinal hemorrhage: A critical analysis by funduscopic examination revealed that 30% to
60% of those sleeping above 5000 meters had retinal hemorrhages. The initial effect includes retinal vascular
engorgement and tortuousness. Optic disc hyperemia is also noted, and multiple flame-shaped hemorrhages
subsequently occur. These changes are reversible.

High-altitude flatus: Changes in external pressure and production of intestinal gas provide for expansion
of intestinal luminal contents and lead to increased flatus at altitudes above 3500 meters. No medical disease
attends these changes, but social problems have been encountered.

Acute mountain sickness: This condition is rare below 2500 meters but occurs to some degree in nearly
everyone at 3000 to 3600 meters. Initial presentation includes headache, lassitude, anorexia, weakness, and
difficulty sleeping. The underlying pathophysiology is in part related to hypoxia and shifts in plasma fluid to
the interstitial space. Adaptation through increased respiratory rate causes some improvement. Descent to lower
altitudes is certainly indicated. Chronic or subacute exacerbation of this disease also occurs, frequently at lower
altitudes, and the symptoms may be severe.

High-altitude deterioration: Generally occurring at very high elevations (5500 meters or more), highaltitude deterioration presents as a decrease in physical and mental performance. The combination of chronic
hypoxia, inadequate fluid intake, inadequate nutrition, decreased plasma volume, and hemoconcentration are
aggravating factors.

High-altitude pulmonary edema and cerebral edema: Serious high-altitude problems, including
pulmonary edema and cerebral edema, can occur with a rapid ascent to heights over 2500 meters, particularly in
susceptible persons who have difficulty sleeping at higher altitudes. Tachycardia, right ventricular overload,
and marked reduction in arterial oxygen pressure occur, without changes in pH or carbon dioxide retention.
Pulmonary hypertension is common in patients with high-altitude pulmonary edema. Hypoxic vasoconstriction
and intravascular thrombosis have been proposed as causes of pulmonary hypertension. Eventually, cardiac
output is decreased and systemic blood pressure falls. The precapillary arterioles become dilated, increasing
capillary bed pressure and inducing interstitial and alveolar edema.

High-altitude encephalopathy is characterized by confusion, stupor, and coma. A proposed mechanism
is severe cerebral hypoxia, with inhibition of the sodium pump and resultant intracellular edema.
3. Injury by chemical agents
With heightened awareness of the fact that chemical agents may mediate tissue changes. There is a nearly endless list
of chemical agents that can be injurious when inhaled, ingested, injected, or absorbed through the skin. The great majority
had either minor or no toxic effects. In this chapter we concentrate on diseases caused by exposure to toxic agents.
Classification of Chemicals Causing Injury
Several groups of chemicals have been implicated as causes of disease.
Chemicals of Abuse
Ethyl alcohol, tobacco, and psychotropic drugs such as narcotics, cocaine, amphetamines, sedatives, marijuana, and so
forth are common drugs of abuse. Drug abuse is an age-old problem. The list of drugs of abuse grows as so-called
designer drugs are developed in an attempt to increase the range of psychotropic effects provided by other licit and illicit
drugs.
Therapeutic Drugs
Prescribed drugs may also cause injury through adverse side effects or drug interactions, overdosage, improper use,
etc.
Industrial and Agricultural Chemicals
Metals, insecticides, herbicides, and many chemicals produced as by-products of industrial processes and disposed of
at toxic waste sites constitute a major public health hazard. Toxic waste has contaminated groundwater supplies and fauna
in some areas. Various toxic chemicals are also present as constituents of common household products such as
insecticides, cleaners, and detergents.
Mechanisms of Human Exposure
Voluntary Abuse
Addicts voluntarily use habituating substances because of physiologic or psychologic dependence. Psychotropic drugs
are also used sporadically by nonaddicts as a means of either escaping reality or experiencing unusual sensory
phenomena.
Suicide or Homicide
Drugs may be taken or surreptitiously administered with suicidal or homicidal intent. The types of drugs used for these
purposes vary with locale as well as with time—eg, arsenic was commonly used for murder and suicide in Roman times,
whereas insecticides, cyanide, carbon monoxide, sedatives, and acet-aminophen are more commonly used today.
Accidental Ingestion
Toxic chemicals, particularly household products, may be accidentally ingested by young children, and such incidents
are an important cause of death in this age group. Accidental ingestion may occur in any age group if containers of toxic
substances or the substances themselves are inadvertently switched or mislabeled.
Occupational Exposure
Exposure to toxic chemicals is common in agricultural and industrial workers. Although various safety guidelines have
been developed to protect workers, some exposure is inevitable. Pathologists, for example, handle specimens that have
been fixed with formalin; the formaldehyde vapors emanating from such specimens have been shown to be toxic. Lowlevel exposure to formaldehyde is therefore an occupational hazard for pathologists.
Incidental, Unrecognized Inadvertent Exposure
Exposure to trace levels of toxic chemicals in food (eg, nitrites used as preservatives in meats), drinking water (toxic
pollutants in ground water supplies), and air (ozone, oxides of nitrogen in smog, and passive smoking) is a major potential
cause of disease. Further studies are needed to define the extent of this threat.
The following principles are important in understanding the mechanisms of chemical injury:

Dose. In general, the higher the dose, the greater the toxicity, although small doses may cause serious
sequelae, particularly over a protracted period. An example is impairment of mental development in children
chronically exposed to low levels of lead.

Requirement for metabolic conversion. Some agents (e.g., certain alkaline cleaning materials) are
directly toxic to cells and hence injure the mucosa of the oral cavity, esophagus, and stomach when swallowed.
In contrast, many drugs, including alcohol, are converted in the liver to compounds that are more toxic than the
parent compound. Thus, there may be little or no injury to the site of entry, and the liver may bear the brunt of
injury.

Sites of absorption, accumulation, or excretion. These may be the targets of maximal injury. For
chemicals that are direct cell toxins, the site of entry is obviously important in determining the type of injury.
The site of accumulation is also important. The aminoglycoside antibiotics, for instance, are particularly prone
to accumulate in the endolymph and perilymph of the ear and in the renal cortex, thus explaining the propensity
of these drugs (e.g., tetracycline) to cause ototoxicity and nephrotoxicity.

Individual variation. An important determinant of the rate of drug metabolism is inherited
polymorphisms in the enzymes that metabolize the drugs. For example, acetylation of the antihypertensive drug
hydralazine is genetically determined. Individuals who are slow acetylators are more likely to develop druginduced lupus.

The capacity of the chemical to induce an immune response. Many chemicals are not directly toxic but
inflict injury by inducing an immune response. For example, penicillin may induce an immunoglobulin E (IgE)mediated anaphylactic response or an IgG-mediated hemolytic anemia in those who are genetically prone to
develop type I or type II hypersensitivity reactions to this drug.
Tobacco smoke
Tobacco smoking is a self-inflicted major health hazard worldwide. Although all forms of tobacco are
implicated-cigars, pipes, snuff-the principal offender is cigarettes. The World Health Organization reported that
in 1998 there were about 1235 billion adult smokers in a world population of 5926 billion and that the number
of smokers can be expected to increase to 1671 billion in 2020. The following discussion summarizes (1) the
detrimental effects of cigarette smoking, (2) the reversal of these effects with cessation of smoking, and (3) the
evidence that passive smoke inhalation is also injurious to health.
The number of potentially noxious chemicals in tobacco smoke is extraordinary. The table rovides only a
partial list and includes the likely mechanism by which each of these agents produces injury. This injury
translates into a number of important diseases. The major diseases responsible for excess mortality reported in
cigarette smokers are, in order of frequency, coronary heart disease, lung cancer, and chronic obstructive
pulmonary disease. Cancers of the oral cavity, larynx, esophagus, pancreas, bladder, kidney, colon, and cervix
are all more common in smokers than in nonsmokers. Also, smokers show excess mortality from
atherosclerotic aortic aneurysms and peptic ulcer disease.
Tabl 2 Effects of selected tobacco smoke constituents.
Substance
Effect
Tar
Carcinogenesis
Polycyclic aromatic hydrocarbons Carcinogenesis
Nicotine
Ganglionic stimulation and depression, tumor promotion
Phenol
Tumor promotion and irritation
Benzopyrene
Carcinogenesis
Carbon monoxide
Impaired oxygen transport and utilization
Formaldehyde
Toxicity to cilia and irritation
Oxides of nitrogen
Toxicity to cilia and irritation
Nitrosamine
Carcinogenesis
We should point out here some of the mechanisms for these diseases. Agents in smoke have a direct irritant
effect on the tracheobronchial mucosa, producing inflammation and increased mucus production (bronchitis).
Cigarette smoke also results in the recruitment of leukocytes to the lung, with increased local elastase
production and subsequent injury to lung tissue, leading to emphysema. Components of cigarette smoke,
particularly tars with their polycyclic hydrocarbons, are potent experimental carcinogens and cancer promoters
and are likely involved in the origins of cancers in the lung arising from the bronchial epithelium (bronchogenic
carcinoma). The risk of development of these diseases is related to the intensity of exposure, frequently
expressed in terms of "pack years" (e.g., one pack daily for 20 years equals 20 pack years). Moreover, smoking
multiplies the risk of other carcinogenic influences; witness the 10-fold increased incidence of bronchogenic
carcinoma in asbestos workers who smoke over those who do not smoke.
In addition to lung disease, atherosclerosis and its major complication, myocardial infarction, have also been
strongly linked to cigarette smoking; causal mechanisms likely relate to several factors, including increased
platelet aggregation, decreased myocardial oxygen supply (because of significant lung disease coupled with the
hypoxia related to the carbon monoxide content of cigarette smoke) accompanied by an increased oxygen
demand, and a decreased threshold for ventricular fibrillation. Almost one third of all heart attacks are
attributed to cigarette smoking. Smoking has a multiplicative effect when combined with hypertension and
hypercholesterolemia.
As might be expected, cessation of smoking leads to substantial benefits. The overall risk of dying in
individuals of all ages is increased if the individuals smoke but is reduced somewhat within a year after
quitting. The risk of lung cancer continues to decrease for at least 15 years but does not disappear.
Maternal smoking increases the risk of spontaneous abortions and preterm births and results in intrauterine
growth retardation; birth weights of infants born to mothers who stopped smoking before pregnancy are normal.
Breathing sidestream smoke (passive smoke inhalation) is also associated with some of the same detrimental
effects that result from active smoking. It is estimated that the relative risk of lung cancer in nonsmokers
exposed to environmental smoke is about 1.3 times that of nonsmokers who are not exposed to smoke. Even
more striking is the increased risk of coronary atherosclerosis and fatal myocardial infarction. Children living in
a household with an adult who smokes have an increased incidence of respiratory illnesses and asthma. It is
clear that the transient pleasure a puff may give comes with a heavy long-term price.
Alcohol and drags of abuse
Drug abuse may be defined as the use of mind-altering substances in a way that differs from generally
approved medical or social practices. Ethanol is imbibed, at least partly, for its mood-altering properties but
when used in moderation is socially acceptable and not injurious. When excessive amounts are used, alcohol
can cause marked physical and psychologic damage. Table provides a classification of drugs that are abused,
with examples of each. Our purpose here is to describe the lesions directly associated with the abuse of alcohol
and with illicit drug use.
Table 3. Classification of drugs of abuse
Class
Examples
Sedatives and hypnotics
Alcohol, barbiturates, benzodiazepines
CNS
sympathomimetics
or Cocaine, amphetamines, methylphenidate (Ritalin), weight loss products
stimulants
Opioids
Heroin, morphine, methadone, and almost all prescription analgesics
Cannabinols
Marijuana, hashish
Hallucinogens or psychedelics
Lysergic acid diethylamide (LSD), mescaline, psilocybin, phencyclidine
(PCP)
Inhalants
Aerosol sprays, glues, toluene, gasoline, paint thinner, amyl nitrite, nitrous
oxide
Nonprescription drugs
Ingredients: Atropine, scopolamine, weak stimulants, antihistamines,
weak analgesics
Ethanol
Despite all the attention given to cocaine and heroin addiction, alcohol use and abuse are a more widespread
hazard and claim many more lives. Fifty percent of adults in the Western world drink alcohol, and about 5% to
10% have chronic alcoholism. It is broadly estimated that alcohol is responsible for 100,000 deaths annually in
the United States, most often caused by cirrhosis of the liver, which is the fourth most frequent cause of death
among people 25 to 64 years of age.
After consumption, ethanol is absorbed unaltered in the stomach and small intestine. It is then distributed to
all the tissues and fluids of the body in direct proportion to the blood level. Less than 10% is excreted
unchanged in the urine, sweat, and breath. The amount exhaled is proportional to the blood level and forms the
basis of the breath test employed by law enforcement agencies.Most of the alcohol in the blood is
biotransformed to acetaldehyde by alcohol dehydrogenase in the cytosol of cells in the liver and gastric mucosa
and with rising blood levels also by cytochrome P-450 (CYP2E1) and catalase in the liver. In the course of
these reactions, nicotinamide adenine dinucleotide (NAD) is reduced to NADH. The acetaldehyde is then
converted to acetic acid. A number of metabolic consequences follow from the biotransformations:The ethanol
is a substantial source of energy (empty calories), and this leads to malnutrition and deficiencies, particularly of
the B vitamins. Vitamin deficiency is common in chronic alcoholics and includes deficiencies of vitamin A
(tobacco-alcohol amblyopia [visual loss]), thiamin (Wernicke's encephalopathy, Korsakoff's psychosis),
folic acid (megaloblastic anemia), and pyridoxine (sidero-blastic anemia).

Excess NADH contributes to acidosis, reduces excretion of uric acid, opposes gluconeogenesis, and
inhibits fatty acid oxidation, having secondary effects on the liver.

Acetaldehyde has many adverse effects and may in fact be responsible for the damage wreaked on many
organs (especially the liver and brain) by chronic alcoholism.The blood alcohol level is determined by the
amount and rate of ethanol consumed and the rate of metabolism. Drowsiness occurs at 200 mg/dL, stupor at
300 mg/dL, and coma, with possible respiratory arrest, at higher levels. The rate of metabolism obviously
affects the blood alcohol level. Persons with chronic alcoholism can tolerate levels of up to 700 mg/dL,
partially explained by a five- to tenfold increased induction of the cytochrome P-450 enzyme system in the
liver. The elevated enzyme levels increase the metabolism of other drugs as well, such as cocaine and
acetaminophen. Conversely, there are genetic polymorphisms involving these enzymes that lower their
metabolic rate of function (e.g., women have lower levels of gastric alcohol dehydrogenase than men,
accounting for the fact that they tend to get "drunk" more readily).
The adverse effects of ethanol must be divided into its acute actions and the consequences of chronic
alcoholism.
Acute alcoholism exerts its effects mainly on the central nervous system, but it may induce hepatic and
gastric changes that are reversible in the absence of continued alcohol consumption. The gastric changes
constitute acute gastritis and ulceration. In the central nervous system, alcohol is a depressant, first affecting
subcortical structures (probably the high brain stem reticular formation) that modulate cerebral cortical activity.
Consequently, there is stimulation and disordered cortical, motor, and intellectual behavior. At progressively
higher blood levels, cortical neurons and then lower medullary centers are depressed, including those that
regulate respiration. Respiratory arrest may follow.
Whatever the basis, people with chronic alcoholism suffer significant morbidity and a shortened life span,
related principally to damage to the liver, gastrointestinal tract, central nervous system, cardiovascular system,
and pancreas.

Liver. Alcohol, the most common cause of hepatic injury, may lead to cirrhosis.

Gastrointestinal tract. Massive bleeding from gastritis, gastric ulcer, or esophageal varices (associated
with cirrhosis) may prove fatal.

Central nervous system. A deficiency of thiamine is common in chronic alcoholic patients; the principal
lesions of this deficiency are peripheral neuropathies and the Wernicke-Korsakoff psychosis. (characterized by
retrograde amnesia and confabulatory symptoms). Cerebral atrophy, cerebellar degeneration, and optic
neuropathy may also occur, possibly directly related to alcohol or its products.

Cardiovascular system. Alcohol has diverse effects on the heart. Direct injury to the myocardium may
produce dilated congestive cardiomyopathy. On the other hand, moderate amounts of alcohol (one drink/day)
have been observed to increase levels of HDL and inhibit platelet aggregation, lowering the incidence of
coronary heart disease. But heavy consumption, with attendant liver injury, results in decreased levels of HDL,
increasing the likelihood of coronary heart disease. Chronic alcoholism is also associated with an increased
incidence of hypertension.Pancreas. Excess alcohol intake increases the risk of acute and chronic pancreatitis.

Other effects. The use of ethanol during pregnancy-as little as one drink per day-can cause fetal alcohol
syndrome (i.e., growth retardation and some reduction in mental functions in the newborn). Chronic alcohol
consumption is associated, on epidemiologic grounds, with an increased incidence of cancer of the oral cavity,
esophagus, liver, and, possibly, breast in females. How it acts is uncertain, but it is believed that ethanol itself,
or the metabolite acetaldehyde, acts as a tumor promoter rather than a direct carcinogen.It is evident that
alcohol has wide-ranging unpleasant consequences.Cocaine
There has been a major escalation in the use of cocaine, along with its derivative "crack"; The
pharmacologic actions of cocaine and crack are identical, but crack is far more potent. Both forms of the drug
are absorbed from all sites and so can be snorted, smoked after mixing with tobacco, ingested, or injected
subcutaneously or intravenously.Cocaine produces an intense euphoria with so-called reinforcing qualities,
making it one of the most addictive of all drugs. In the cocaine abuser, although physical dependence appears
not to occur, the psychologic withdrawal is profound and can be extremely difficult to treat. The most serious
physical effects of cocaine relate to its acute action on the cardiovascular system, where it behaves as a
sympathomimetic. It facilitates neurotransmission both in the central nervous system, where it blocks the
reuptake of dopamine, and at adrenergic nerve endings, where it blocks the reuptake of both epinephrine and
norepinephrine while stimulating the presynaptic release of norepinephrine. The net effect is the accumulation
of these two neurotransmitters in synapses, resulting in excess stimulation, manifested by tachycardia and
hypertension. Cocaine also induces myocardial ischemia, the basis for which is multifactorial. It causes
coronary artery vasoconstriction, promotes thrombus formation by facilitating platelet aggregation, and induces
premature atherosclerosis in long-term users. Cocaine-induced coronary vasospasm is potentiated by cigarette
smoking. Thus, on the one hand, cocaine induces increased myocardial oxygen demand by its
sympathomimetic action; on the other hand, it reduces coronary blood flow, thus setting the stage for
myocardial ischemia that may lead to myocardial infarction. In addition to its detrimental effects on myocardial
oxygenation, cocaine can also precipitate lethal arrhythmias by enhanced sympathetic activity as well as by
disrupting normal ion (K+, Ca++, Na+) transport in the myocardium. These toxic effects are not necessarily doserelated, and a fatal event may occur in a first-time abuser with what is a typical mood-altering dose. The
following are some manifestations of acute cocaine toxicityCerebral infarction and intracranial hemorrhage
may develop the latter in persons who have preexisting vascular malformations and probably related to the
sudden acute elevations in blood pressure. The most common central nervous system findings are hyperpyrexia
(thought to be caused by aberrations of the dopaminergic pathways that control body temperature) and
seizures.Rhabdomyolysis, sometimes accompanied by renal failure may be observed. The mechanism is not
understood but may relate to intense vasoconstriction together with a direct effect of the drug on muscle.In
pregnant women, decreased blood flow to the placenta may be causing fetal hypoxia and spontaneous abortion.
In chronic users of the drug, fetal neurologic development may be impaired.In contrast to acute toxicity,
chronic cocaine use may result in (1) perforation of the nasal septum in cocaine snorters, (2) decreased lung
diffusing capacity in those who inhale the smoke from cocaine, and (3) rarely, the development of dilated
cardiomyopathy.Heroin
Heroin is even more hazardous than cocaine. Heroin is an addictive opioid derived from the poppy plant and
closely related to morphine. As sold on the street, it is cut (diluted) with an agent (often talc or quinine); thus,
the size of the dose is not only variable but also usually unknown to the buyer. The heroin, along with any
contaminating substances, is usually self-administered intravenously or subcutaneously. Effects are varied and
include euphoria, hallucinations, somnolence, and sedation. Heroin has a wide range of adverse physical effects
related to (1) the pharmacologic action of the agent, (2) reactions to the cutting agents or contaminants, (3)
hypersensitivity reactions to the drug or its adulterants (quinine itself has neurologic, renal, and auditory
toxicity), and (4) diseases contracted incident to the use of the needle.

Sudden death, usually related to overdose, is an ever-present risk because drug purity is generally
unknown. Sudden death can also occur if tolerance for the drug, built up over time, is lost (as during a period of
incarceration). The mechanisms of death include profound respiratory depression, arrhythmia and cardiac
arrest, and severe pulmonary edema.

Pulmonary complications include moderate to severe edema, septic embolism, lung abscess,
opportunistic infections, and foreign body granulomas from talc and other adulterants. Although granulomas
occur principally in the lung, they are sometimes found in the mononuclear phagocyte system, particularly in
the spleen, liver, and lymph nodes that drain the upper extremities. Examination under polarized light often
highlights trapped talc crystals, sometimes enclosed within foreign body giant cells.

Infectious complications are common. The four sites most commonly affected are the skin and its
subcutaneous tissue, heart valves, liver, and lungs.

Cutaneous lesions are probably the most frequent telltale sign of heroin addiction. Acute changes
include abscesses, cellulitis, and ulcerations owing to subcutaneous injections. Scarring at injection sites,
hyperpigmentation over commonly used veins, and thrombosed veins are the usual sequelae of repeated
intravenous inoculations.

Kidney disease is a relatively common hazard. The two forms most frequently encountered are
amyloidosis and focal glomerulosclerosis; both induce heavy proteinuria and the nephrotic syndrome.
Amyloidosis is secondary to chronic skin infections.
Marijuana
Marijuana, or "pot," is the most widely used illegal drug. It is made from the leaves of the Cannabis sativa
plant, which contain the psychoactive substance tetrahydrocannabinol (THC). When it is smoked, about 5% to
10% is absorbed. Despite numerous studies, the central question of whether the drug has persistent adverse
physical and functional effects remains unresolved. Some of the untoward anecdotal effects may be allergic or
idiosyncratic reactions or may possibly be related to contaminants in the preparations rather than to marijuana's
pharmacologic effects. On the other hand, two beneficial effects of THC are its capacity to decrease intraocular
pressure in glaucoma and to combat intractable nausea secondary to cancer chemotherapy.

The functional and organic central nervous system consequences of marijuana have received greatest
scrutiny. Clearly, the use of pot distorts sensory perception and impairs motor coordination, but these acute
effects generally clear in 4 to 5 hours. With continued use, these changes may progress to cognitive and
psychomotor impairments, such as inability to judge time, speed, and distance. Among adolescents, such
changes often lead to automobile accidents.

Not unexpectedly, the lungs are affected by chronic pot smoking; laryngitis, pharyngitis, bronchitis,
cough and hoarseness, and asthma-like symptoms have all been described, along with mild but significant
airway obstruction. Smoking a marijuana cigarette, compared with a tobacco cigarette, is associated with a
threefold increase in the amount of tar inhaled and retained in the lungs. Presumably, the larger puff volume,
deeper inhalation, and longer breath holding are responsible. Long-term smokers of marijuana may also be at
increased risk for lung cancer.
Marijuana increases the heart rate and sometimes blood pressure and in a person with a fixed coronary artery
narrowing may cause angina.
Marijuana may induce chromosomal damage in somatic and germ cells, but the evidence is not
incontrovertible. A large study involving many thousands of female marijuana users revealed lower infant birth
weights, shorter gestational periods, and an increased number of malformations among the offspring. Because
the peak use of marijuana is among teenagers and young adults, these provocative findings require further
study.
Other Illicit Drugs
The variety of drugs that have been tried by those seeking "new experiences" defies belief. They range from
various stimulants (e.g., amphetamines) to depressants (e.g., benzodiazepines) to hallucinogens (e.g.,
phenylcyclohexyl piperidine [PCP], "ecstasy"). Because they are used haphazardly and in various
combinations, little is known of their long-time deleterious effects, but this much is clear-they are a dangerous
combination with alcohol and driving!
Iatrogenic Drug Injury
Iatrogenic drug injury refers to the unintended side effects of therapeutic or diagnostic drugs prescribed by
physicians. Adverse reactions to pharmaceuticals are surprisingly common. They are seen in 2% to 5% of
patients hospitalized on medical services; of these reactions, 2% to 12% are fatal. The typical hospitalized
patient is given about 10 different medications, and some receive five times as many. The risk of an adverse
reaction increases proportionately with the number of different drugs; Untoward effects of drugs result from (1)
overdose, (2) exaggerated physiological responses, (3) a genetic predisposition, (4) hypersensitivity, (5)
interactions with other drugs, and (6) other unknown factors.
4. Injury Caused by biological factors
Infectioun of humans may be caused by bacteria, viruses, mycoplasmas, rickettsiae, chlamydiae, fungi, and
protozoa. Some of these organisms infect humans through direct access, such as inhalation, whereas others
infect through transmission by an intermediate vector, such as from an insect bite.
Cells of the body may be destroyed directly by these agents or by a toxin released from the microorganism,
or may be indirectly injured as a result of the immune and inflammatory reactions stimulated in response to the
microorganism. In addition, infection of a cell by a microorganism may so destabilize the cell that it undergoes
apoptosis.
Bacteria
Bacteria are free-living, one-celled organisms that reproduce on their own, but use animal hosts for nutrient
access. Bacteria stimulate the inflammatory and immune response and often release toxins specifically
damaging to the host.
Studies have shown that human susceptibility to some bacterial infections is genetically controlled. Other
superimposing variables that influence bacterial infectivity include host nutritional status, co-infections,
exposure to environmental microbes, and previous vaccinations.
Viruses
Viruses, unlike bacteria, require a host to reproduce. A virus consists of a single strand of DNA or RNA that
is contained within a protein coat called a capsid. Viruses must bind to the host cell membrane, enter the cell,
and then move into the host cell nucleus to reproduce. Once inside the nucleus, viral DNA can become
incorporated into the host cell DNA, thus ensuring that viral genes will be passed to each daughter cell during
mitosis. Once in the DNA, the virus begins to take over the functions of the cell. RNA viruses also begin to
control cell function after their translation into proteins.
Certain types of viruses can enter the host DNA and remain latent for years, producing infections
occasionally or not at all. Viruses that remain latent include all those of the herpes family, including the herpes
viruses responsible for varicella (chickenpox), zoster (shingles), cytomegalovirus, mononucleosis, and the
herpes simplex viruses. A unique type of virus is the retrovirus. These viruses are RNA viruses that can
incorporate into the host DNA as a result of the action of the enzyme reverse transcriptase that changes the viral
RNA into DNA. Retroviruses carry reverse transcriptase as part of their structure. Examples of human disease
caused by retroviruses include acquired immunodeficiency syndrome (AIDS), caused by the human
immunodeficiency virus (HIV), and a form of leukemia, HTLV-I. Retroviruses also may remain dormant for
long periods of time.
Mycoplasmas
Mycoplasmas are unicellular microorganisms similar in action to bacteria except much smaller and without
the peptidoglycan cell wall. Because many antibiotics (e.g., the penicillins) act by destroying the peptidoglycan
cell wall, mycoplasmas are insensitive to these antibiotics.
Examples of human disease caused by mycoplasmas include mycoplasma pneumonia, upper respiratory tract
infections, and some genital infections.
Rickettsiae
Rickettsiae require a host to asexually reproduce. They contain RNA and DNA inside a rigid peptidoglycan
cell wall. Rickettsiae are transmitted to humans through the bite of the flea, tick, or louse. Examples of human
disease caused by rickettsiae include typhus and Rocky Mountain spotted fever.
Chlamydiae
Chlamydiae are unicellular organisms that reproduce asexually inside a host cell. They transmit directly to
humans and undergo cycles of replication. Human diseases caused by chlamydiae include a sexually
transmitted urogenital infection and pneumonia.
Fungi
Fungi include yeast and molds. Fungi contain a nucleus and are surrounded by a rigid cell wall. Fungi
usually do not cause disease in healthy humans, and some fungi are considered normal human flora. Most
fungal infections are superficial, but some may be deep, causing infection of vital organs and tissues.
Parasites
The term parasite refers to protozoa, helminths, and arthropods.
Protozoans are unicellular organisms capable of causing infections. Infection is passed directly between
individuals through contaminated food or water, or through an insect vector. Examples of human disease
caused by protozoans include malaria and the intestinal disease giardiasis.
Helminths are worms that require a host to sexually reproduce. Transmission to humans occurs through
ingestion or penetration of the skin. Examples of human disease caused by helminths include roundworm
(nematodes) and tapeworm (cestodes). Helminths are a significant problem in developing countries.
Arthropods are ticks and mosquitoes that act as vectors to carry diseases to humans. Examples of human
disease carried by arthropods include bubonic plague (caused by a bacillus) and typhus (caused by a rickettsia).
Other arthropods infect and damage body surfaces by their bite or burrowing. Arthropods that infect body
surfaces include lice, scabies, chiggers, and fleas.
Results of Infection
The entry and multiplication of an infectious agent in a host represents an infection. In a subclinical infection, there is
no clinically apparent disease but the body shows evidence of an immune response against the agent, usually by the
development of antibodies. In such cases, the host response probably controls the infection rapidly. A clinical infectious
disease results when tissue damage occurs. Many infectious diseases are acute, with a rapid outcome ending either in
complete recovery or death; some progress to chronic disease. The aim of physicians is to influence the natural history of
an infectious disease in favor of recovery; this requires accurate diagnosis of the agent that is causing the disease and
appropriate treatment when such is available.
When infection occurs, the expression of the disease in a given patient can also vary greatly, depending on host
factors. In the majority of infectious diseases, infection is localized to the portal of entry of the agent, eg, streptococcal
pharyngitis. In a few cases, organisms enter the lymphatics or the bloodstream and disseminate in the body. The
frequency and ease with which a given organism causes disseminated infection is a function of the virulence of the
organism and the immune status of the host.
In most infectious diseases, the host develops an immune response. This involves both humoral and cellular
immunity and is usually beneficial to the host in providing immunity against future infection with the same
agent. Immunity against many viruses is lifelong, while that due to bacteria and fungi is more transient. In some
cases, the immune response itself results in disease even after the infection has been controlled. The best
example of this is streptococcal infection, where the immune response may cause injury to the heart (acute
rheumatic fever) and glomeruli (acute poststreptococcal glomerulonephritis). These pathologic events occur
without entry of streptococci into the bloodstream or infection of these tissues by streptococci.
Poststreptococcal glomerulonephritis is caused by deposition in the glomeruli of soluble immune complexes
formed in the blood between streptococcal antigens and antibodies.