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MOD II > Chapter 9: Environmental and Nutritional Diseases > Flashcards

Chapter 9: Environmental and Nutritional Diseases Flashcards

1
Q

Sources of CO2 causing climate change

A

Burning of fossil fuels, ozone, methane–these gases along with water vapor produce the green house effect by absorbing/re-emitting infrared energy; also increased by deforestation, increase n surface heat absorption due to loss of ice, increase in water vapor due to greater evaporation, decreased sequestration of CO2 in oceans due to reduced organisms, increased heat energy in oceans and atmosphere

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2
Q

A quantatitative concept of a poison strictly depends on?

A

Dosage

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3
Q

Exogenous chemicals in the environment in air, water, food and soil that may be absorbed into the body through inhalation, ingestion and skin contact

A

Xenobiotics

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4
Q

Most solvents and drugs are ____philic which facilitates their transport in the blood by _____ and their penetration through the plasma membrane into cells

A

Lipo

Lipoproteins

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5
Q

_____ estimates the burden imposed by environmental disease, including communicable disease, and nutritional diseases by applying a metric called DALY (disability adjusted life year)–Sum of years of life lost due to premature mortality and years of life lost to disability in a population

A

GBD–Global Burden of Disease, a world health organization project

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6
Q

Most solvents and drugs absorbed by the body go one of either two paths. They can be detoxified by obtaining _____ properties or they can be activated to form toxic metabolites

A

Water soluble

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7
Q

Phases that occurs in metabolism

A

Phase I: chemicals undergo hydrolysis, oxidation or reduction
Phase II: products of phase I become conjugated onto something (this makes them water soluble–examples are glucoronidation, sulfation, methylation, and conjugation with glutathione

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8
Q

Most important catalyst of phase I reactions

A

CYP (cytochrome P 450 enzyme system)

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9
Q

Where is P-450 located?

A

Primarily in endoplasmic reticulum in liver but also present in skin, lungs, and GI mucosa and other organs

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10
Q

The P-450 system catalyzes reactions that either detoxify cenobitic so or less commonly covert xenobiotics into active compounds that cause cellular injury. Which one causes ROS?

A

Both may produce ROS as byproduct

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11
Q

In the United States, the environmental protection agency monitors and sets allowable upper limits for what six pollutants?

A 
Sulfur dioxide
Carbon monoxide
Ground level ozone
Nitrogen dioxide
Lead 
Particulate matter
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12
Q

Which ozone is the good one and which is the bad?

A

Good=O3

Bad=ground level ozone

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13
Q

What does O3 do? What does ground level ozone do?

A

Ozone (O3) is produced by interaction of UV radiation and oxygen in the stratosphere and protects life on earth by absorbing the most dangerous UV radiation emitted by the sun

It is a gas formed by the reaction of nitrogen and volatile organic compounds (industrial and motor vehicle exhaust) in the presence. It’s toxicity is mediated by the production of free radicals, which injure epithelial cells along the respiratory tract and type I alveolar cells

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14
Q

Conditions caused by exposure to chemical or physical agents in the ambient, workplace and personal environment including diseases of nutritional origin. Diseaase related to environmental exposures mostly comes to publics attention after dramatic events

A

Environmental disease

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15
Q

Single leading global cause of health loss

A

Undernutrition

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16
Q

Leading causes of death in developed nations

A

Undernutrition

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17
Q

Major risk factors of coronary and cerebrovascular diseases

A

Obesity, smoking and high cholesterol

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18
Q

5 of the top 10 causes of death in developing countries are what?

A

Infectious diseases–respiratory infection, HIV, diarrheal disease, TB, malaria

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19
Q

Malnutrition increases the risk of?

A

Infection

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20
Q

50% of all death in children younger than 5 are attributable to what 3 conditions (all preventable)

A

Pneumonia, diarrheal diseases, and malaria

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21
Q

Type of diseases constitute almost 1/3 of newly emerging infections and in many cases can be linked to environmental changes including global warming?

A

Vector borne diseases

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22
Q

How has worldwide mortality of under 5 yo children changed since 1980?

A

27% decline but does not meet UN goals yet. Under 5 year old mortality in central and west Africa has not declined

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23
Q

3 examples of emerging infectious diseases

A
  1. Newly evolved strains of organisms (MRSA, XDF TB, chloroquine-resistant malaria)
  2. Endemic in other species that have recently entered human population (HIV and SARS)
  3. Present in human populations but show a recent increase in incidence (dengue fever)
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24
Q

4 aspects of health and disease affected by global warming

A
  1. Increase in vector borne disease (dengue fever, west Nile, hanavirus pulmonary syndrome)
  2. Malnutrition: due to disrupted crops
  3. Gastroenteritis and infectious disease epidemics–due to contamination after natural disasters
  4. Cardiovascular, cerebrovascular, respiratory disease–heat waves and air pollution
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25
Q

Most solvents are drugs are of what chemical category?

A

Lipophilic, facilitating transport in blood by lipoproteins and penetration through PM into cells

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26
Q

2 phases of bio transformation of xenobiotics

A

Phase I–P450 (CYP family) catalyzes hydrolysis, oxidation or reduction. Concentrated in ER of liver cells. Can either detoxify or activate xenobiotics.

Phase 2: glucuronidation, sulfation, methylation and conjugation with glutathione

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27
Q

What can be produced in Phase I reactions that is harmful to cells?

A

ROS

Example: trichloromethyl free radical from CCl4, DNA binding metabolite from Benzo-a-pyrene in cigarette smoke

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28
Q

Inducers of CYP

A

Environmental chemicals, drugs, smoking a, EtOH and hormones

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29
Q

What decreases CYP activity?

A

Fasting or starvation

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30
Q

Mechanism of inducers of CYP

A
  1. Bind nuclear receptors
  2. Heterodimerize with retinoic X receptor
  3. Form transcriptional activation complex in 5’ flanking region of CYP genes
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31
Q

What nuclear receptors participate in CYP induction?

A

Rayo hydrocarbon receptor, peroxisome proliferator-activated receptors and two orphan nuclear receptors (androstane receptor and pregnant X receptor)

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32
Q

6 pollutants in outdoor air

A
  1. Ozone
  2. Sulfur dioxide
  3. Nitrogen dioxide
  4. Carbon monoxide
  5. Lead
  6. Particulate matter
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33
Q

Health effects of ozone exposure

A

Damage mediated by free radicals, injuring respiratory epithelial cells and type 1 alveolar cells with inflammatory mediator. Decreased lung function, chest discomfort, ozone-induced asthma (airway hyper-reactivity and neutrophilia)

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34
Q

Health effects of ozone exposure

A

Damage mediated by free radicals, injuring respiratory epithelial cells and type 1 alveolar cells with inflammatory mediator. Decreased lung function, chest discomfort, ozone induced asthma (airway hyper reactivity and neutrophilia)

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35
Q

Health effects of sulfur dioxide exposure

A

Converted into sulfuric acid and sulfuric trioxide burning sensation in nose and throat, dyspnea, asthma attacks

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36
Q

Health effects of particulate matter (aka soot)

A

Fine or ultra fine particles less than 10um in diameter are most harmful. Inhaled into alveoli leading to release of inflammatory mediators (macrophage inflammatory protein 1 alpha, and endothelin) irritation to eyes, throat, lungs, induce asthma attacks, promote myocardial ischemia

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37
Q

What gets damaged most markedly in chronic carbon monoxide poisoning?

A

Ischemia in CNS, especially basal ganglia and lenticular nuclei—leads to impaired memory, vision, hearing and speech

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38
Q

Symptoms of acute CO poisoning

A

Characteristic generalized cherry-red color of skin and MM brain edema, punctate hemorrhages, hypoxia–induced neuro changes

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39
Q

8 examples of indoor air pollutants

A
  1. Tobacco smoke
  2. CO
  3. NO2
  4. Asbestos
  5. Wood smoke
  6. Bio aerosols
  7. Radon
  8. Formaldehyde
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40
Q

Health effects of bioaerosol exposure

A

Microbes causing legionnaires disease, viral pneumonia, cold allergens from pet dander, dust mites, and fungi/molds–>rhinitis, eye irritation, and asthma

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41
Q

Health effects of radon exposure

A

Lung cancer

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42
Q

Health effects of formaldehyde

A

0.1 ppm or higher–>dyspnea, burning in eyes and throat, asthma; carcinogen

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43
Q

Four heavy metals most commonly associated with harmful effects in humans

A
  1. Lead
  2. Mercury
  3. Arsenic
  4. Cadmium
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44
Q

Health problems associated with sub clinical lead poisoning

A

Low intellectual capacity, behavior problems etc

45
Q

At about twice the max allowed level of lead, what health problems can develop?

A

Increased nerve conduction velocity, increased level of erythrocytes protoporphyrin, decreased vitamin D metabolism, and decreased calcium homeostasis

46
Q

At about 4x the max allowed level of lead, what problems occur?

A

Decreased hemoglobin synthesis

47
Q

At about 10x the max allowed level of lead, what health problems develop?

A

Encephalopathy, nephropathy, frank anemia, and colic?

48
Q

Where is most lead absorbed into?

A

Bone and developing teeth

49
Q

Why are children more susceptible to lead poisoning than adults?

A

Higher intestinal absorption (50% vs. less than 15) and more permeable blood brain barrier

50
Q

Bone consequences of lead poisoning in children

A

Interferes with normal remodeling of cartilage and primary bone Trabeculae in epiphysis, causing radio dense lead lines of increased bone density–also appears in gums

Inhibits healing of function by increasing chondrogenesis and delaying cartilage mineralization

51
Q

Hematopoietic consequences of lead poisoning in children

A

Inhibits delta aminoelvulinic acid dehydratase and ferrocene latest–>microcytic hypochromic anemia

52
Q

What is used to diagnose lead poisoning?

A

Detection of elevated blood levels of lead and free (or zinc bound) red cell protoporphyrin

53
Q

Morphological changes in lead poisoning

A
  1. Ringed sideroblasts (iron-laden mitochondria) in marrow
  2. Microcytic hypochromic anemia with mild hemolysis
  3. Punctate basophilic stippling of RBCs
54
Q

CNS and PNS changes in lead poisioning

A

CNS: brain edema, demyelination of cortical neurons, diffuse astrocytic proliferation

PNS: peripheral demyelinating neuropathy in motor nerves of most commonly used muscles–wrist drop and foot drop

55
Q

GI and renal changes in lead poisoning

A

GI: lead colic
Renal: proximal tubular damage, interstitial fibrosis, renal failure, saturnine gout

56
Q

Which organ is especially susceptible to methyl mercury?

A

Developing CNS due to lipid solubility. Binds with high affinity to thiol groups

57
Q

What is the main protective mechanism against Mercury-induced CNS and kidney damage?

A

Intracellular glutathione acting as a thiol donor

58
Q

Arsenic trioxide is used to treat what disease?

A

Relapsing acute promo elocution leukemia

59
Q

three most toxic forms of arsenic

A
  1. Arsenic trioxide
  2. Sodium arsenite
  3. Arsenic trichloride
60
Q

Mechanism of arsenic toxicity

A

Interference with mitochondrial ox phos, since trivalent arsenic can replace the phosphates in ATP

61
Q

Neurological effects of arsenic toxicity

A

2-8 weeks after exposure, sensorimotor neuropathy–paresthesias, numbness and pain

62
Q

Most serious consequence of chronic arsenic exposure

A

Development of cancer in almost all tissues, particularly lungs and skin

63
Q

Skin changes in arsenic exposure

A

Hyper pigmentation and hyperkeratosis–>basal and squamous cell carcinoma. Appears on palms and soles (unlike skin tumors induced by sunlight)

64
Q

Mechanism of cadmium toxicity

A
  1. Obstructive lung disease, due to necrosis of Alvolar macrophages
  2. Kidney damage, due to tubular damage progressing to ESRD
  3. Skeletal problems, due to calcium loss. (Osteoporosis and osteomalacia)
  4. Elevated risk of lung cancer due to ROS causing DNA damage
65
Q

Vinyl chloride associated disease

A

Liver angiosarcoma

66
Q

Poly chlorinated biphenyls, dioxins, and herbicides: associated diseases

A

Folliculitis and acneiform dermatosis

67
Q

Benzene and 1,3-butadiene: associated disease

A

Leukemia

68
Q

Chemicals associated with male infertility

A

Lead, phthalate plasticizers, and cadmium

69
Q

Chemicals associated with female infertility/stillbirths

A

Lead and Mercury

70
Q

Chemicals associated with teratogenesis

A

Mercury, polychlorinated biphenyls

71
Q

Chemicals associated with urinary system toxicity

A

Mercury, lead, glycol ethers, solvents

72
Q

Chemicals associated with bladder cancer

A

Napthylamines, 4-amino biphenyl, Benzedine, rubber products

73
Q

Chemicals associated with peripheral neuropathies

A

Solvents, acrylamide, methyl chloride, Mercury, lead, arsenic

74
Q

Chemical associated with ataxic gait

A

DDT

75
Q

Chemicals associated with CNS depression

A

Chlordane, toluene, acrylamide, Mercury

76
Q

Chemicals associated with cataracts

A

Alcohols, ketones, aldehydes, solvents, UV

77
Q

Chemicals associated with respiratory fibrosis

A

Silica, asbestos, cobalt

78
Q

Chemicals associated with respirator irritation

A

Ammonia, sulfur oxides, formaldehyde

79
Q

Chemicals associated with respiratory hypersensitivity

A

Beryllium, isocyanates

80
Q

Chemicals associated with COPD

A

Grain dust, coal dust, cadmium

81
Q

Chemicals associated with lung cancer

A

Radon, asbestos, silica, bis (chloromethyl) ether, nickel, arsenic, chromium, mustard gas, uranium

82
Q

chemicals associated with nasal cancer

A

Isopropyl EtOH, wood dust

83
Q

Chemicals associated with heart disease

A

CO, lead, solvents, cobalt, cadmium

84
Q

How is benzene metabolized?

A

Hepatic CYP2E1 to toxic metabolites that disrupt differentiation of hematopoietic cells in bone marrow–>aplasia and acute myeloid leukemia

85
Q

Polycyclic hydrocarbons: diseases associated

A

Lung and bladder cancer

86
Q

Examples of organochlorides

A
  1. Endocrinopathies, having anti-estrogen or anti androgen effects
  2. Folliculitis and chloracne dermatosis
  3. PCBs induce CYPs–>abnormal drug metabolism
87
Q

Inhalation of mineral dusts cause what disease

A

Pneumoconioses: chronic, non-neoplastic lung disease

88
Q

Toxins in tobacco smoke

A

Tar, polycyclic aromatic hydrocarbons, phenol, benzopyrene, nitrosamine (carcinogenesis and tumor promotion), CO, nicotine, formaldehyde and nitrogen oxides (toxic to cilia)

89
Q

What two drugs interact in forming laryngeal cancer

A

Tobacco and EtOH

90
Q

How is ethanol metabolized?

A

Biotransformed into acetaldehyde in liver by alcohol dehydrogenase (mainly), microsomal ethanol-oxidizing system and catalase
ADH in cytosol of hepatocytes. Then acetaldehyde is converted to acetate by acetaldehyde dehydrogenase (ALDH) MEOS involves CYPs (esp CYP2E1)

91
Q

What produces a majority of the toxic effects of alcohol consumption

A

Acetaldehyde–responsible for acute effects of EtOH and for developing oral Cancer

92
Q

Allelic variation of what enzyme affects 50% of Asians?

A

ALDH–very low ALDH activity due to base substitution (ALDH2x2) of one allele

93
Q

People who cannot oxidize acetaldehyde have what abnormal enzyme?

A

Homozygous for ALDH*2; nausea, flushing, tachycardia, and hyperventilation

94
Q

What causes hepatic steatosis and lactic acidosis in alcoholics

A

Increased NADH/NAD ratio

95
Q

How do gram negative bacteria in intestinal flora respond to alcohol?

A

Release of endotoxin (LPS) to stimulate TNF production and cytokines from macrophages and Kuppffer cells–>hepatic injury

96
Q

Gastric changes in acute alcholism

A

Gastritis and ulceration

97
Q

CNS changes in acute alcoholism

A

Depressant, first affecting su cortical structures (high brain stem reticular formation) modulating cerebral cortical activity. At higher levels, cortical neurons and then lower medullary centers are depressed

98
Q

What vitamin deficiency is common in alcoholics?

A

Thiamine (vitamin B1); causing peripheral neuropathies and Wernicke-Korsakoff syndrome

99
Q

CV effects of alcohol

A

Dilated congestive cardiomyopathy; heavy EtOH causes decreased levels of HDL and HTN

100
Q

EtOH is most harmful during which trimester of pregnancy?

A

First

101
Q

Mechanism of EtOH induced laryngeal and esophageal cancer?

A

Acetaldehyde-DNA adducts

102
Q

People with this allele who drink alcohol are at higher risk of developing esophageal cancer

A

One copy of ALDH2*2 allele

103
Q

What compound in red wine may have protective effects against CV disease?

A

Resveratrol activates protein deacetylases of the sir2 family, including histones deacetylases

104
Q

Estrogen therapy alone is only used in these pateints

A

Hysterectomized women increased risk of uterine cancer in other patients

105
Q

Findings by the WHI in 2002

A

Combined therapy caused a reduction in function but increased risk of breast cancer and thromboembolism; no effect in preventing CV disease in patients over 60. 10 million drop in therapy in 5 year

106
Q

HRT: Risk highest and latency times shorter for developing these cancers:

A

Lobular carcinomas and ductal-lobular carcinoma

107
Q

CV protective effect of HRT based on

A

Younger women: response of estrogen receptors regulating calcium homeostasis in blood vessels

108
Q

Four types of diseases associated with OCs

A
  1. Thromboembolism: due to generation of acute phase response with increase in CRP and coagulation factors and reduction in anticoagulants
  2. Reduce incidence of endometrial and ovarian cancer and small increase of breast cancer

MOD II (3 decks)

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