Pathological Anatomy and Physiology

Week 6

Environmental and Nutritional Diseases

The environmental factors that influence our health pertain to individual behavior (“personal environment”) and include tobacco use, alcohol ingestion,
recreational drug consumption, diet, and the like, or the external (ambient and workplace) environment. In general, in developed countries personal
behavior has a larger effect on health than the ambient environment.

Environmental Effects on Global Disease Burden

A comparison of causes of morbidity and mortality from 1990 to 2010 generated by the GBD project has revealed the following trends:
• On a worldwide basis, there were dramatic increases in mortality due to HIV/AIDS and associated infections, which peaked in 2006.

• Undernutrition is the single leading global cause of health loss (defined as morbidity and premature death).
•
• Ischemic heart disease and cerebrovascular disease remain the leading causes of death in developed countries.

• In developing countries, five of the 10 leading causes of death are infectious diseases: respiratory infections, human immunodeficiency virus/acquired
immunodeficiency syndrome (HIV/AIDS), diarrheal diseases, tuberculosis, and malaria
• .
• In the postnatal period, about 50% of all deaths in children younger than 5 years of age are attributed to only three conditions, all preventable:
pneumonia, diarrheal diseases, and malaria.
•
 Health Effects of Climate Change
Without immediate action, climate change stands to become the preeminent global cause of environmental disease in the twenty-first century and beyond.
The health impacts of climate change will depend on its extent and rapidity, the nature and severity of the ensuing consequences, and humankind’s
ability to mitigate the damage. Even in the best case scenario, however, climate change is expected to have a serious negative impact on human health by
increasing the incidence of a number of diseases, including the following:
• Cardiovascular, cerebrovascular, and respiratory diseases,all of which will be worsened by heat waves and airpollution

• Gastroenteritis, cholera, and other foodborne and waterborne infectious diseases, caused by contamination as a consequence of floods and disruption
of clean water supplies and sewage treatment, after heavy rains and other environmental disasters

• Vector-borne infectious diseases, such as malaria and dengue fever, due to changes in vector number and geographic distribution related to increased
temperatures, crop failures, and more extreme weather variation.

• Malnutrition, caused by changes in local climate that disrupt crop production. Such changes are anticipated to be most severe in tropical locations, in
which average temperatures may already be near or above crop tolerance levels;
 Toxicity of Chemical and Physical Agents
Toxicology is defined as the science of poisons. It studies the distribution, effects, and
mechanisms of action of toxic agents.

Environmental Pollution
Air Pollution
Air pollution is a significant cause of morbidity and mortality worldwide, particularly among at-risk
individuals with preexisting pulmonary or cardiac disease. Air is precious to life, but can also carry many
potential causes of disease. Airborne microorganisms have long been major causes of morbidity and
mortality, especially in developing countries. More widespread are airborne chemical and particulate
pollutants, especially in industrialized nations.

Outdoor Air Pollution

The ambient air in industrialized nations is contaminated with an unsavory mixture of gaseous and
particulate pollutants, more heavily in cities and in proximity to heavy industry. In the United States, the
Environmental Protection Agency monitors and sets allowable upper limits for six pollutants: sulfur
dioxide, carbon monoxide, ozone, nitrogen dioxide, lead, and particulate matter. Collectively, these agents
produce the well-known smog (smoke and fog) that sometimes stifles large cities such as Beijing, Los
Angeles, Houston, Cairo, New Delhi, Mexico City, and São
Paulo. It may seem that air pollution is a modern phenomenon, but this is hardly the case.

Indoor Air Pollution

The most common pollutant is tobacco smoke. Volatile substances containing polycyclic aromatic
hydrocarbons generated by cooking oils and coal burning are important indoor pollutants in ome regions
of China.
• Wood smoke
• Bioaerosols range from microbiologic agents capable of causing infectious diseases such as egionnaires
disease, viral pneumonia, and the common cold.
• Radon, a radioactive gas derived from uranium widely present in soil and in homes, can cause lung
cancer in uranium miners.
 Effects of Tobacco
Smoking is the most readily preventable cause of death in humans.
The main culprit is cigarette smoking, but smokeless tobacco (e.g., snuff,
chewing tobacco) is also harmful to health and an important cause of oral
cancer. The use of tobacco products not only creates personal risks, but passive
tobacco inhalation from the environment (“second-hand smoke”) can cause
lung cancer in nonsmokers.
Indeed, tobacco is the leading exogenous cause of human cancers, including
90% of lung cancers.
The only good news is that cessation of smoking greatly reduces, within 5
years, overall mortality and the risk of death from cardiovascular diseases. Lung
cancer mortality decreases by 21% within 5 years, but the excess risk persists
for 30 years.

Smoking and Lung Cancer.

Agents in smoke have a direct irritant effect on the tracheobronchial mucosa,
producing inflammation and increased mucus production (bronchitis).
Cigarette smoke also causes 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 polycyclic
hydrocarbons and nitrosamines (Table 9-4), are potent carcinogens in animals
and are directly involved in the development of lung cancer in humans.
• Cigarette smoking is associated with cancers of the esophagus, pancreas,
bladder, kidney, cervix, and bone marrow.
• Cigarette smoking is also strongly linked to the development of
atherosclerosis and its major complication, myocardial infarction.
• In addition to having deleterious effects on the smoker, smoking also harms
the developing fetus. Maternal smoking by delivering vaporized nicotine
and flavorings, which are rising in popularity.
 Effects of Alcohol
Ethanol consumption in moderate amounts is generally not injurious (and may
even protect against some disorders), but in excessive amounts alcohol causes
serious
physical and psychological damage.
Despite all the attention given to illicit drugs such as cocaine and heroin, alcohol
abuse is a far more widespread hazard and claims many more lives. Fifty percent
of adults in the Western world drink alcohol, and about 5% to 10% have
chronic alcoholism.
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 used by law enforcement agencies.
Most of the alcohol in the blood is oxidized to acetaldehyde in the liver by three
enzyme systems consisting of alcohol dehydrogenase, the microsomal ethanol-
oxidizing system, and catalase.
The main enzyme system involved in alcohol metabolism is alcohol
dehydrogenase,
located in the cytosol of hepatocytes.
The adverse effects of ethanol can be classified as acute or chronic.
Acute alcoholism exerts its effects mainly on the CNS, but it may induce hepatic
and gastric changes that are reversible if alcohol consumption is discontinued.
Even with moderate intake of alcohol, multiple fat droplets accumulate in the
cytoplasm of hepatocytes (fatty change or hepatic steatosis).
The gastric changes are acute gastritis and ulceration. In the CNS, 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.
Chronic alcoholism affects not only the liver and stomach, but virtually all
other organs and tissues as well. Chronic alcoholics suffer significant morbidity
and have a shortened life span, related principally to damage to the liver,
gastrointestinal tract, CNS, cardiovascular system, and pancreas.
• The liver is the main site of chronic injury. In addition to fatty change
mentioned above, chronic alcoholism causes alcoholic hepatitis and
cirrhosis.
• In the gastrointestinal tract, chronic alcoholism can cause
massive bleeding from gastritis, gastric ulcer, or esophageal varices
(associated with cirrhosis), which may be fatal
• Thiamine (vitamin B1) deficiency is common in chronic alcoholics. The
principal lesions resulting from this deficiency are peripheral neuropathies
and the Wernicke Korsakoff syndrome.
• Alcohol has diverse effects on the cardiovascular system.
Injury to the myocardium may produce dilated congestive cardiomyopathy
(alcoholic cardiomyopathy,)
• Excessive alcohol intake increases the risk of acute and chronic
pancreatitis.
• The use of ethanol during pregnancy can cause fetal alcohol syndrome,
which is marked by microcephaly, growth retardation, and facial
abnormalities in the newborn, and reduction in mental functions as the
child grows older. It is difficult to establish the minimal amount of alcohol
consumption that can cause fetal alcohol syndrome, but consumption
during the first trimester of pregnancy is particularly harmful.
• chronic alcohol consumption is associated with an increased incidence of
cancer of the oral cavity, esophagus, liver, and, in women, possibly the
breast. Acetaldehyde is considered to be the main agent associated with
alcohol-induced laryngeal and esophageal cancer, in that acetaldehyde-
DNA adducts have been detected in some tumors from these tissues.
 Injury by Therapeutic Drugs and Drugs of Abuse

Adverse drug reactions refer to untoward effects of drugs that are given in conventional therapeutic settings.
• Anticoagulants: The principal complications associated with both of these medications are bleeding, which can be fatal, and thrombotic complications
such as embolic stroke stemming from undertreatment.
• Menopausal Hormone Therapy (MHT)
• Oral Contraceptives (OCs)
• Anabolic Steroids: Anabolic steroids are synthetic versions of testosterone, and for performance enhancement they are used at doses that are about 10
to 100 times higher than therapeutic indications.
• Aspirin (Acetylsalicylic Acid)

Cocaine
Cocaine is extracted from the leaves of the coca plant, and is usually prepared as a water-soluble powder, cocaine hydrochloride.
The acute and chronic effects of cocaine on various organ systems
are as follows:
• Cardiovascular effects. The most serious physical effects of cocaine
relate to its acute action on the cardiovascular system, where it behaves
as a sympathomimetic. (tachycardia, hypertension, and peripheral
vasoconstriction. )Cocaine may also induce myocardial ischemia by
causing
• coronary artery vasoconstriction and by enhancing platelet aggregation
and thrombus formation.
• CNS. The most common acute effects on the CNS are hyperpyrexia
(thought to be caused by aberrations of the dopaminergic pathways
that control body temperature) and seizures.
• Effects on pregnancy. In pregnant women, cocaine may cause acute
decreases in blood flow to the placenta, resulting in fetal hypoxia and
spontaneous abortion. Neurologic development may be impaired in the
fetus of pregnant women who are chronic drug users.
• Other effects. Chronic cocaine use may cause
(1) perforation of the nasal septum in snorters,
(2) decreased lung diffusing capacity in those who inhale the smoke, and
(3) development of dilated cardiomyopathy.
Opiate drugs of abuse include synthetic prescription opiates such as
oxycodone (OxyContin) and “street drugs,” most notably heroin. Heroin is an
addictive opioid derived from the poppy plant that is closely related to
morphine. Its use is even more harmful than that of cocaine. 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. Heroin, along with any contaminating
substances, is usually self-administered intravenously or subcutaneously. The
effects on the CNS are varied and include euphoria, hallucinations,
somnolence, and sedation.
• Sudden death. Sudden death, usually related to overdose, is an ever-
present risk, because drug purity is generally unknown (ranging from 2%
to 90%).
• Pulmonary injury. Pulmonary complications include moderate to severe
edema, septic embolism from endocarditis, lung abscess, opportunistic
infections, and foreign-body granulomas from talc and other adulterants.
• Infections. Infectious complications are common. The
four sites most commonly affected are the skin and subcutaneous tissue,
heart valves, liver, and lungs.
• Skin. Cutaneous lesions are probably the most frequent telltale sign of
heroin addiction. Acute changes include abscesses, cellulitis, and
ulcerations due to subcutaneous injections. Scarring at injection sites,
hyperpigmentation over commonly used veins, and thrombosed veins are
the usual sequelae of repeated intravenous inoculations.
• Kidneys. Kidney disease is a relatively common hazard. The two forms
most frequently encountered are amyloidosis (generally secondary to skin
infections) and focal and segmental glomerulosclerosis; both induce
proteinuria and the nephrotic syndrome.
 Marijuana
Marijuana is made from the leaves of the Cannabis sativa plant, which
contain the psychoactive substance Δ9- tetrahydrocannabinol (THC).
About 5% to 10% of THC is absorbed when it is smoked in a hand-
rolled cigarette
(“joint”). Despite numerous studies, the central question of whether the
drug has persistent adverse physical and functional effects remains
unresolved.
With continued use these changes may progress to cognitive and
psychomotor impairments, such as inability to judge time, speed, and
distance, a potential cause of automobile accidents. Marijuana increases
the heart rate and sometimes blood pressure, and it may cause angina in
a person with coronary artery disease.
• The respiratory system is also affected by chronic marijuana
smoking; laryngitis, pharyngitis, bronchitis, cough and hoarseness,
and asthma-like symptoms have all been described, along with mild
but significant airway obstruction. Marijuana cigarettes contain a
large number of carcinogens that are also present in tobacco.
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 because of the larger puff
volume, deeper inhalation, and longer breath holding
 Nutritional Diseases
Dietary Insufficiency

There are several conditions that may lead to primary or secondary malnutrition.
• Poverty. Homeless persons, aged individuals, and children of the poor often suffer from
PEM as well as trace nutrient deficiencies. In poor countries, poverty, crop failures,
livestock deaths, and drought, often in times of war and political upheaval, create the
setting for the malnourishment of children and adults.
• Infections. PEM increases susceptibility to many common infectious diseases.
Conversely, infections have a negative effect on nutrition, thus establishing a vicious
cycle.
• Acute and chronic illnesses. The basal metabolic rate becomes accelerated in many
illnesses resulting in increased daily requirements for all nutrients. Failure to recognize
these nutritional needs may delay recovery.
PEM is often present in patients with wasting diseases, such as advanced cancers and
AIDS (discussed later).
• Chronic alcoholism.
• Ignorance and failure of diet supplementation. Even the affluent may fail to recognize
that infants, adolescents, and pregnant women have increased nutritional needs.
Ignorance about the nutritional content of various foods is also a contributing factor.
• Self-imposed dietary restriction. Anorexia nervosa, bulimia, and less overt eating
disorders affect many individuals who are concerned about body image and are obsessed
with body weight.
Vitamin A Deficiency. Vitamin A deficiency occurs worldwide either as a consequence of general undernutrition or as a secondary deficiency in individuals
with conditions that cause malabsorption of fats. In children, stores of vitamin A are depleted by infections, and the absorption of the vitamin is poor in newborn
infants. Adult patients with malabsorption syndromes, such as celiac disease, Crohn disease, and colitis, may develop vitamin A deficiency, in conjunction with
depletion of other fat-soluble vitamins. Bariatric surgery and, in older persons, continuous use of mineral oil as a laxative may lead to deficiency.
As already discussed, vitamin A is a component of rhodopsin and other visual pigments. Not surprisingly, one of the earliest manifestations of vitamin A
deficiency is impaired vision, particularly in reduced light (night blindness). Other effects of deficiency are related to the role of vitamin A in maintaining the
differentiation of epithelial cells. Persistent deficiency gives rise to epithelial metaplasia and keratinization. The most devastating changes occur in the eyes and
are referred to as xerophthalmia (dry eye). First, there is dryness of the conjunctiva (xerosis conjunctivae) as the normal lacrimal and mucus-secreting epithelium
is replaced by keratinized epithelium. This is followed by a buildup of keratin debris in small opaque plaques (Bitot spots) that progresses to erosion of the
roughened corneal surface, softening and destruction of the cornea (keratomalacia), and blindness.
 Obesity
Excess adiposity (obesity) and excess body weight are associated with increased incidence of several of the most important diseases of humans, including type 2
diabetes, dyslipidemias, cardiovascular disease, hypertension, and cancer. Obesity is defined as an accumulation of adipose tissue that is of sufficient magnitude to
impair health. As with weight loss, excess weight is best assessed by the body mass index, or BMI. For practical reasons, body weight, which
generally correlates well with BMI, is often used as a surrogate for BMI measurements. The normal BMI range is 18.5 to 25 kg/m2, although the range may differ
for different countries. Individuals with BMI greater than 30 kg/m2
are classified as obese;
Obesity is a major public health problem in developed countries and an emerging health problem in developing nations, such as India.
At its simplest level, obesity is a disease of caloric imbalance that results from an excess intake of calories that exceeds their consumption by the body. However,
the pathogenesis of obesity is complex and incompletely understood. Ongoing research has identified intricate humoral and neural mechanisms that control
appetite and satiety. These neurohumoral mechanisms respond to
genetic, nutritional, environmental, and psychologic signals, and trigger a metabolic response through the stimulation of centers located in the hypothalamus.
There is little doubt that genetic influences play an important role in weight control, but obesity is a disease that depends on the interaction between multiple
factors. After all, regardless of genetic makeup, obesity would not occur without intake of food.