Path Book: Chapter 7 Environmental and Nutritional Diseases pg. 268-287

Question 1

What is an environmental disease?

Answer 1

disorders caused by exposure to chemical or physical agents in the ambient, workplace, and personal environments, including diseases of nutritional origin.

Question 2

Climate change is expected to have a serious negative impact on human health by increasing the incidence of a number of diseases, including:

Answer 2

• Cardiovascular, cerebrovascular, and respiratory diseases, all of which will be exacerbated by heat waves and air pollution.
• Gastroenteritis, cholera, and other food- and water- borne 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 tempera- tures, crop failures and more extreme weather variation (e.g., more frequent and severe El Niño events)
• 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; it is estimated that by 2080, agricultural productivity may decline by 10% to 25% in some developing countries as a consequence of climate change.

Question 3

What is Toxicology?

Answer 3

the science of poisons. It studies the distribution, effects, and mechanisms of action of toxic agents. More broadly, it also includes the study of the effects of physical agents such as radiation and heat.

Question 4

What are Xenobiotics?

Answer 4

exogenous chemicals in the environment that may be absorbed by the body through inhalation, ingestion, or skin contact

Question 5

Most solvents and drugs are _____.

Answer 5

lipophilic, which facilitates their transport in the blood by lipoproteins and penetration through lipid components of cell membranes.

Question 6

What are the phases of xenobiotic metabolism?

Answer 6

In phase I reactions, chemicals can undergo hydrolysis, oxidation, or reduction. Products of phase I reactions often are metabolized into water-soluble compounds through phase II reactions of glucuronidation, sulfation, methylation, and conjugation with glutathione (GSH). Water-soluble compounds are readily excreted.

Question 7

The most important cellular enzyme system involved in phase I reactions is the _____.

Answer 7

cytochrome P-450 system

Question 8

Where is the cytochrome P450 system located?

Answer 8

primarily in the endoplasmic reticulum (ER) of the liver but also present in skin, lungs, and gastrointestinal (GI) mucosa and in practically every organ.

Question 9

What is a possible byproduct of metabolism?

Answer 9

production of reactive oxygen species (ROS), which can cause cellular damage

Question 10

What are some things that impact P450 efficacy?

Answer 10

1) Genetic polymorphisms
2) Dietary practices (fasting, etc.)
3) Smoking or alcohol

Question 11

In the United States, the Environmental Protection Agency (EPA) monitors and sets allowable upper limits for what six pollutants?

Answer 11

sulfur dioxide, CO, ozone, nitrogen dioxide, lead, and particulate matter.

Question 12

How does ozone exposure damage the body?

Answer 12

major impact on the lungs. it participates in chemical reactions that generate free radicals, which injure the lining cells of the respiratory tract and the alveoli.

Question 13

T or F. Low levels of ozone don’t impact people

Answer 13

Low levels of ozone may be tolerated by healthy persons but are detrimental to lung function, especially in those with asthma or emphysema, and when present along with particulate pollution

Question 14

Sulfur dioxide, particles, and acid aerosols are emitted mainly by what processes?

Answer 14

coal- and oil-fired power plants and industrial processes burning these fuels.

Question 15

Of these, particles appear to be the main cause of morbidity and death. Particles less than 10 μm in diameter are particularly harmful. Why?

Answer 15

since when inhaled they are carried by the airstream all the way to the alveoli before there is any mechanism to contain/eliminate them

By contrast, larger particles are removed in the nose or are trapped by the mucociliary “escalator” and as a result are less dangerous.

Question 16

What happens when small particulate matter reaches the alveoli?

Answer 16

They are phagocytosed by macrophages and neutrophils, causing the release of mediators and inciting an inflammatory reaction.

Question 17

How does CO cause toxicity?

Answer 17

CO is a systemic asphyxiant that kills by binding to hemoglobin and preventing oxygen transport. Hemo- globin has a 200-fold greater affinity for CO than for O2.

Question 18

What does CO interaction with hemoglobin result in?

Answer 18

Carboxyhemoglobin that is incapable of carrying oxygen.

Question 19

Systemic hypoxia appears when the hemoglobin is ___ to ___ saturated with CO, and unconsciousness and death are probable with 60% to 70% saturation.

Answer 19

20% to 30%

Question 20

Can Chronic (low level inhalation over a long time) poisoning by CO kill you? As opposed to rapid influx of CO as in most accidental death and suicides (aka acute poisoning)?

Answer 20

Yes, CO toxicity develops because carboxyhemoglobin, once formed, is very stable. As a result, with low-level persistent exposure to CO, carboxyhemoglobin may accumulate to a life-threatening concentration in the blood. The slowly developing hypoxia can insidiously evoke widespread ischemic changes in the brain

Question 21

Can people chronically exposed to CO recover once the source is eliminated?

Answer 21

With cessation of exposure to CO, the patient usually recov- ers, but there may be permanent neurologic damage.

sometimes impairments of memory, vision, hearing, and speech may remain.

Question 22

How is CO poisoning diagnosed?

Answer 22

The diagnosis of CO poisoning is based on detection of high levels of carboxyhemoglobin in the blood.

Question 23

How would ‘acute’ CO poisoning appear in light skin people?

Answer 23

In light-skinned people, it is marked by a characteristic generalized cherry- red color of the skin and mucous membranes, a color imparted by carboxyhemoglobin.

Question 24

What are some common indoor pollutants?

Answer 24

1) Cigarette and wood smoke
2) Radon
3) Bioaerosols

Question 25

What are some common heavy metal toxins?

Answer 25

lead, mercury, arsenic, and cadmium

Question 26

How does lead exposure occur?

Answer 26

through contaminated air and food. For most of the 20th century the major sources of lead in the environment were house paints and gasoline.

burned batteries, paint, etc.

Question 27

What is the difference between lead absorption in children and adults?

Answer 27

Children absorb more than 50% of lead from food, while adults absorb approximately 15%. A more permeable blood–brain barrier in children creates a high susceptibility to brain damage.

Question 28

What are the main clinical features of lead poisoning?

Answer 28

brain: headache and memory loss in adults and mental deterioration in children. Peripheral neuropathies predominate in adults, while central effects are more common in children (low IQ).
gingiva: lead line
blood: anemia

peripheral nerves: demyelination in adults

GI pain, radiodense deposits in epiphyses in children

Question 29

Most of absorbed lead (80% to 85%) is taken up and stored where?

Answer 29

bone and developing teeth; lead competes with calcium, binds phosphates, and has a half-life in bone of 20 to 30 years.

About 5% to 10% of the absorbed lead remains in the blood, and the remainder is distributed throughout soft tissues.

Question 30

T or F. The effects of lead exposure are reversible in adults and children

Answer 30

F. Lead-induced peripheral neuropathies in adults generally remit with elimination of expo- sure, but both peripheral and CNS abnormalities in children usually are irreversible.

Question 31

What are ‘lead lines’ in the gums?

Answer 31

excess lead stimulates hyperpigmentation

Question 32

How is lead excreted?

Answer 32

kidneys. Acute exposures may cause damage to proximal tubules.

Question 33

Why does lead exposure lead to anemia? 2 ways

Answer 33

Lead has a high affinity for sulfhydryl groups and interferes with two enzymes involved in heme synthesis, aminolevulinic acid dehydratase and delta ferrochelatase. Iron incorporation into heme is impaired, leading to anemia

Lead also inhibits sodium- and potassium-dependent ATPases in cell membranes, an effect that may increase the fragility of red cells, causing hemolysis.

Question 34

How is lead poisoning diagnosed?

Answer 34

Elevated blood lead and red cell free protoporphyrin (formed instead of heme) levels (greater than 50 μg/dL) or, alternatively, zinc-protoporphyrin levels (formed instead of heme), are required

Question 35

The anemia associated from lead poisoning is accompanied by what?

Answer 35

basophilic stippling of red cells

Question 36

What are the main sources of mercury?

Answer 36

contaminated fish and dental amalgams, which release mercury vapors.

Question 37

What are some common symptoms of mercury poisoning?

Answer 37

tremor, gingivitis, and bizarre behavior

Question 38

What is mercury especially dangerous to? What can it lead to?

Answer 38

The developing brain is very sensitive to methyl mercury; pregnant women should avoid the consumption of fish known to contain mercury.

can lead to Minamata disease, characterized by cerebral palsy, deafness, and blindness.

Question 39

Ingestion of arsenic impacts what biological processes?

Answer 39

mitochondrial oxidative phosphorylation.

Question 40

Common symptoms of arsenic poisoning?

Answer 40

If ingested in large quantities, arsenic causes acute toxicity manifesting as severe gastrointestinal, cardiovascular, and central nervous system disturbances, often progressing to death.

Chronic exposure to arsenic causes hyperpigmentation and hyperkeratosis of the skin, which may be followed by the development of basal and squa- mous cell carcinomas (but not melanomas).

Question 41

Where are arsenic induced skin tumors commonly found?

Answer 41

Arsenic-induced skin tumors differ from those induced by sunlight by appearing on palms and soles, and by occurring as multiple lesions

Question 42

What is a common source of cadmium?

Answer 42

It is used mainly in nickel- cadmium batteries, which generally are disposed of as household waste. It can contaminate soil and plants directly or through fertilizers and irrigation water.

Question 43

What are the main symptoms of excessive cadmium exposure?

Answer 43

obstructive lung disease and renal toxicity, initially as tubular damage that may progress to end-stage renal disease.

Also, skeletal abnormalities associated with calcium loss.

Cam SNL

Question 44

What effect does excessive acute exposure to organic solvents such as chloroform and carbon tetrachloride have on the body?

Answer 44

Acute exposure to high levels of vapors from these agents can cause dizziness and confusion, leading to CNS depression and even coma.

Lower levels have toxicity for the liver and kidneys.

Question 45

Occupational exposure of rubber workers to benzene and 1,3-butadiene increases the risk of _____.

Answer 45

leukemia.

Question 46

How does benzene exposure increase risk of leukemia?

Answer 46

Benzene is oxidized to an epoxide through hepatic CYP2E1. The epoxide and other metabolites disrupt progenitor cell differentiation in the bone marrow, causing marrow aplasia and acute myeloid leukemia.

Question 47

Exposure to Polycyclic hydrocarbons (found in cigarettes, among other things) may cause:

Answer 47

scrotal, lung, and bladder cancer.

Question 48

Exposure to vinyl chloride, used in the synthesis of poly- vinyl resins, was found to cause:

Answer 48

angiosarcoma of the liver, a rare type of liver tumor.

Question 49

What is the age-survival profile of smokers vs. non-smokers?

Answer 49

While 80% of nonsmokers are alive at age 70, only about 50% of smokers survive to this age

Cessation of smoking greatly reduces the risk of death from lung cancer, and it even has an effect, albeit reduced, on people who stop smoking at age 60.

Question 50

Does nicotine cause smoking related disease?

Answer 50

Nicotine, an alkaloid present in tobacco leaves, is not a direct cause of tobacco-related diseases, but it is highly addictive.

Question 51

How does nicotine work?

Answer 51

Nicotine binds to receptors in the brain and, through the release of catecholamines, is responsible for the acute effects of smoking, such as increased heart rate and blood pressure, and increased cardiac contractility and output.

Question 52

What are the most common disease associated with smoking?

Answer 52

The most common diseases caused by cigarette smoking involve the lung and include emphysema, chronic bronchitis, and lung cancer

Question 53

What is a pack-year?

Answer 53

Eg. one pack daily for 20 years equals 20 pack years

Question 54

Atherosclerosis and its major complication, myocardial infarction, are strongly linked to cigarette smoking. How?

Answer 54

factors including increased platelet aggregation, decreased myocardial oxygen supply (because of lung disease coupled with hypoxia related to CO in cigarette smoke) accompanied by increased oxygen demand, and a decreased threshold for ventricular fibrillation.

Question 55

Where else besides the lungs are susceptible to cancers in smokers?

Answer 55

tobacco smoke contributes to the development of cancers of the oral cavity, esophagus, pancreas, and bladder.

Question 56

What can exacerbate the potential for oral, esophageal, or bladder cancer in smokers?

Answer 56

chronic alcohol consumption

Question 57

How is passive smoke inhalation in non- smokers estimated?

Answer 57

by measuring the blood levels of cotinine, a metabolite of nicotine.

Question 58

What happens in the body when alcohol (ethanol) is ingested?

Answer 58

After consumption, ethanol is absorbed unaltered in the stomach and small intestine and then distributes to all of the tissues and fluids of the body in direct proportion to the blood level.

Question 59

What is the level of BAC that is legal in the US?

Answer 59

A concentration of 80 mg/dL in the blood constitutes the legal definition of drunk driving in most states.

For an average individual, this alcohol concentration may be reached after consump- tion of about eight bottles of beer (6 to 16 g of alcohol per bottle), 12 ounces of wine (9 to 18 g of alcohol per glass), or 6 ounces of whiskey

Question 60

How does chronic alcoholism affect metabolism?

Answer 60

Persons with chronic alcoholism can tolerate levels as high as 700 mg/dL, due in part to accelerated ethanol metabo- lism caused by a 5- to 10-fold increase in induction of the hepatic cytochrome P-450 system

Question 61

Most of the alcohol in the blood is metabolized to acetaldehyde in the liver by three enzyme systems:

Answer 61

alcohol dehydrogenase, cytochrome P-450 isoenzymes, and catalase

Of these, the main enzyme involved in alcohol metabolism is alcohol dehydrogenase, located in the cytosol of hepatocytes.

Question 62

At high blood alcohol levels, however, P450s (located in the ER) are very important. Why?

Answer 62

When alcohol is present in the blood at high concentrations, it competes with other CYP2E1 substrates and may delay the catabolism of other drugs (like cocaine, etc.), thereby potentiating their effects.

Question 63

What then happens to acetaldehyde produced from ethanol metabolism?

Answer 63

Acetaldehyde is converted by acetaldehyde dehydrogenase to acetate, which is utilized in the mitochondrial respiratory chain.

Question 64

Several toxic effects result from ethanol metabolism. Name one.

Answer 64

Alcohol oxidation by alcohol dehydrogenase causes a decrease in nicotinamide adenine dinucleotide (NAD+) and an increase in NADH

Question 65

Why is the conversion of NAD+ to NADH in alcohol metabolism bad?

Answer 65

NAD+ is required for fatty acid oxidation in the liver. Its deficiency is a main cause of fat accumulation in the liver of alcoholics. The increase in the NADH/NAD+ ratio in alcoholics also causes lactic acidosis.

Question 66

Why are Asians more susceptible to the effects of alcohol commonly?

Answer 66

About 50% of Asians express a defective form of acetaldehyde dehydroge- nase. After ingesting alcohol, such persons experience flushing, tachycardia, and hyperventilation owing to the accumulation of acetaldehyde.

Question 67

What is another toxic effect of alcohol metabolism?

Answer 67

Metabolism of ethanol in the liver by CYP2E1 produces reactive oxygen species and causes lipid peroxidation of cell membranes.

Question 68

The adverse effects of ethanol abuse can be categorized as acute or chronic. What are the effects of Acute alcoholism?

Answer 68

cute alcoholism exerts its effects mainly on the CNS but also may induce reversible hepatic and gastric injuries. With moderate intake, multiple fat droplets accumulate in the cytoplasm of hepatocytes (fatty change or hepatic steatosis).

Question 69

What are the effects of chronic alcoholism?

Answer 69

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, GI tract, CNS, cardiovascular system, and pancreas.

Question 70

The ___ is the main site of chronic injury with alcohol. What happens?

Answer 70

liver. Chronic alcoholism causes alcoholic hepatitis and cirrhosis

Question 71

What is hormone replacement therapy (HRT) used for?

Answer 71

Estrogen therapy, once used pri- marily for distressing menopausal symptoms (e.g., hot flashes), has been widely used in postmenopausal women, with or without added progestins, to prevent or slow the progression of osteoporosis and to reduce the likelihood of myocardial infarction.

Question 72

What is the controversy involved with HRT?

Answer 72

Recent data have confirmed the adverse effects of HRT on endometrial and breast cancers but do not support the view that HRT offers protection against ischemic heart disease (it actually increased HDL levels).

Question 73

T or F. HRT with estrogen alone increases the risk of endometrial cancer.

Answer 73

T. Unopposed estrogen therapy increases the risk of endo- metrial carcinoma 3- to 6-fold after 5 years of use and more than 10-fold after 10 years, but the risk is drastically reduced or eliminated when progestins are added to the therapeutic regimen.

HRT with estrogen, with or without progestins, also increases the risk of thromboembolism

Question 74

On the other hand, long- term HRT with estrogens AND progestins is associated with an increased risk of ____.

Answer 74

breast cancer.

Question 75

Do oral contraceptives increase risk of breast carcinoma? Endometrial cancer and ovarian cancer?

Answer 75

breast- no

endometrial and ovarian- they actually protect against these tumors

Question 76

Do oral contraceptives increase risk of cervical cancer?

Answer 76

They can if concurrently infected with HPV

Question 77

Do oral contraceptives increase risk of thromboembolism? Why or why not?

Answer 77

Most studies indicate that OCs, including the newer low-dose (less than 50 μg of estrogen) preparations, are associated with a three- to six-fold increased risk of venous thrombosis and pulmonary thromboembolism resulting from increased hepatic syn- thesis of coagulation factors.

however, the risk of thrombo- embolism associated with OC use is two to six times lower than the risk of thromboembolism associated with pregnancy.

Question 78

Do oral contraceptives increase risk of cardiovascular disease? Why or why not?

Answer 78

It seems that OCs do not increase the risk of coronary artery disease in women younger than 30 years or in older women who are nonsmokers, but the risk does approximately double in women older than 35 years who smoke.

Question 79

Other risk with OCs?

Answer 79

Hepatic adenoma: There is a well-defined association between the use of OCs and this rare benign hepatic tumor, especially in older women who have used OCs for prolonged periods. The tumor appears as a large, solitary, and well-encapsulated mass.

Question 80

How is most acetaminophen (Tylenol) metabolized?

Answer 80

It is mostly conjugated in the liver with glucuronide or sulfate. About 5% or less is metabolized to NAPQI through the hepatic P-450 system.

Question 81

What happens with very large doses of acetaminophen (Tylenol)?

Answer 81

With very large doses, however, NAPQI accumulates, leading to centrilobular hepatic necrosis.

Question 82

The mechanisms of injury produced by NAPQI include:

Answer 82

(1) covalent binding to hepatic proteins and
(2) depletion of reduced glutathione (GSH), resulting in hepatocytes being more susceptible to cell death caused by reactive oxygen species

Question 83

What are the symptoms of acetaminophen (Tylenol) toxicity?

Answer 83

Toxicity begins with nausea, vomiting, diarrhea, and sometimes shock, followed in a few days by appearance of jaundice, dark urine, and clay-colored stools

With serious overdoses, liver failure ensues, and centrilobular necrosis may extend to involve entire lobules; patients often require liver transplantation for survival

Question 84

Treatment for overdose of acetaminophen (Tylenol)?

Answer 84

Overdoses of acetaminophen can be treated in early stages by administration of N-acetylcysteine, which restores GSH.

Question 85

What are the symptoms of aspirin overdose?

Answer 85

At first, respiratory alkalosis develops, followed by a metabolic acidosis that often proves fatal.

Question 86

T or F. In cocaine users, although physical dependence seems not to occur, the psychologic dependence is profound.

Answer 86

T. Intense cravings are particularly severe in the first several months after abstinence and can recur for years.

Question 87

What are the main symptoms associated with cocaine overdose?

Answer 87

seizures, cardiac arrhythmias, and respiratory arrest

Question 88

How does cocaine affect the CV system?

Answer 88

The most serious physical effects of cocaine relate to its acute action on the cardiovascular system.

Cocaine is a sympathomimetic agent, both in the CNS, where it blocks the reuptake of dopamine, and at adrenergic nerve endings, where it blocks the reuptake of both epinephrine and norepi- nephrine while stimulating the presynaptic release of norepinephrine. The net effect is the accumulation of these neurotransmitters in synapses and excessive stimulation, manifested by tachycardia, hypertension, and peripheral vasoconstriction

Question 89

Does cocaine use promote thrombosis?

Answer 89

yes, It causes coronary artery vasoconstriction and promotes thrombus formation by facilitating platelet aggregation.

Question 90

How can cocaine cause myocardial infarction and lethal arrhythmias?

Answer 90

Cocaine also can precipitate lethal arrhythmias by enhanced sympathetic activity as well as by disrupting normal ion (K+, Ca2+, Na+) transport in the myocardium.

These toxic effects are not necessarily dose-related, and a fatal event may occur in a first-time user with what is a typical mood-altering dose.

Question 91

What are the major CNS effects of cocaine?

Answer 91

The most common CNS findings are hyper- pyrexia (thought to be caused by aberrations of the dopaminergic pathways that control body temperature) and seizures.

Question 92

What effect does cocaine use have on a fetus?

Answer 92

In pregnant women, cocaine may cause decreased blood flow to the placenta, resulting in fetal hypoxia and spontaneous abortion. Neurologic development may be impaired in the fetuses of pregnant women who are chronic drug users.

Question 93

Some of the most important adverse effects of heroin are the following:

Answer 93

1) Sudden death owing to differing drug potencies unknown to the buyer

2) Pulmonary disease
3) Infections
4) Skin lesions
5) Renal problems

Question 94

What are some of the beneficial effects of THC?

Answer 94

include its capacity to decrease intraocular pressure in glaucoma and to combat intractable nausea secondary to cancer chemotherapy.

Question 95

What are some adverse effects of THC?

Answer 95

1) Mental distortion
2) increased heart rate and sometimes blood pressure, occasionally leading to angina in a person with coronary artery disease
3) Laryngitis, pharyngitis, bronchitis, cough, hoarseness, and asthma-like symptoms all have been described, along with mild but significant airway obstruction.

Question 96

T or F. Smoking a marijuana cigarette, compared with a tobacco cigarette, is associated with an increase in the amount of tar inhaled and retained in the lungs

Answer 96

T. Up to 3 times, as a consequence of deeper inhalation and longer breath holding.