Environmental and Nutritional Disorders Flashcards
1
Q
Worldwide, dramatic increase in mortality due to ? and assoc infections
A
HIV/AIDS
2
Q
single leading global cause of health loss (morbidity & premature death)
A
Undernutrition
3
Q
leading cause of death in developed countries
A
Ischemic heart disease and cerebral vascular disease
4
Q
In developing countries, 5 of 10 leading causes of death (COD) are ?
A
Infectious disease
5
Q
In the postnatal period, ~50% of all deaths in kids <5yo attributed to 3 conditions which are all preventable
A
Pneumonia, diarrheal disease, malaria
6
Q
estimates the burden imposed by environmental dz, including those caused by communicable & nutritional dzs
A
Global disease burden
7
Q
sum of years of life LOST due to premature mortality & disability in a population
A
Disability adjusted life year (DALY)
8
Q
Trends of the changing burden of disease from 1990-2010:
- Cardiovascular disease = ?
- Neonatal conditions and diarrhea diseases = ?
- HIV/AIDS = ?
- Cancer = ?
A
- Cardiovascular disease = Going up
- Neonatal conditions and diarrhea diseases = Gone down
- HIV/AIDS = Going up a little
- Cancer = Going down
9
Q
Newly evolved strains or organisms
A
Multidrug resistant TB
10
Q
Pathogens endemic to other species that recently “jumped” to human population
A
HIV
11
Q
Pathogens that have been present in human population, but show recent increase in incidence
A
Dengue fever: due to warming, spread into Southern US
12
Q
Diseases worsened by heatwaves & air pollution
A
- Cardiovascular
- Cerebrovascular
- Respiratory diseases
13
Q
Diseases from contamination
from floods & disruption of clean water supplies
A
- Gastroenteritis
- Cholera
- Other foodborne and waterborne infectious diseases
14
Q
Vector-borne infectious dzs
- Increase temp, crop failures, and more extreme weather variations
A
- Malaria
- Dengue fever
15
Q
Disrupted crop production
A
Malnutrition
16
Q
Distribution, effects, and mechanisms of action of toxic agents
- Physical agents: radiation, heat
A
Toxicology
17
Q
Definition of a poison is strictly dependent on ?
A
Dosage
- All substances are poisons; the right dosage differentiates a poison from a remedy
18
Q
Exogenous chemicals in the environment (air, water, food, soil) that may be absorbed into the body (inhalation, ingestions, skin contact)
A
Xenobiotics
19
Q
Most solvents & drugs are ?, facilitating their transport & penetration through the basement membrane
A
lipophilic
20
Q
Most solvents, drugs & xenobiotics metabolized to a ? or activated to form ?
A
- inactive water-soluble product (detoxification)
- toxic metabolites
21
Q
? pounds of toxic chemicals, incl 72 million lbs of unrecognized carcinogens, released per year in the US
A
4 BILLION
22
Q
enzyme system (aka CYP) located primarily in endoplasmic reticulum of the liver is also present in skin, lungs, GI mucosa, & other organs
A
Cytochrome P-450
23
Q
Function of Cytochrome P-450:
• Catalyzes reactions (rxn) that either ?, or less commonly convert xenobiotics into ? that cause cellular injury
- Both types of rxn may prod ?as a byproduct which
can cause cellular damage - Carbon tetrachloride → ? in the liver
- Metabolism of ?
A
- Detoxify xenobiotics
- active compounds (cmpd)
- Both types of rxn may prod REACTIVE OXYGEN SPECIES (ROS) as a byproduct which
can cause cellular damage - Carbon tetrachloride → trichloromethyl free radical in the liver
- Metabolism of acetaminophen, barbiturates, warfarin, anticonvulsants, & EtOH
24
Q
Fasting and starvation can ? CYP (cytochrome P-450) activity
A
Decrease
25
Air pollution is especially hazardous to people with ?
Preexisting pulmonary or cardiac dz
26
Outdoor air pollution, EPA limits on ?
sulfur dioxide, carbon monoxide, ozone, nitrogen dioxide, lead & particulate matter
27
Countries with a lot of smog (smoke plus fog)
Beijing, Los Angeles, Houston, Cairo, New Delhi, Mexico City
| & Sãu Paulo
28
What populations are at risk for ozone pollutants?
- Healthy adults and children
| - Athletes, outdoor workers, and asthmatics
29
What are the effects of ozone pollutant for healthy adults and children?
- Decreased lung function
- Increased airway reactivity
- Lung inflammation
30
What are the effects of ozone pollutant for Athletes and outdoor workers?
Decreased exercise capacity
31
What are the effects of ozone pollutant for Asthmatics?
Increased hospitalizations
32
What populations are at risk for sulfur dioxide pollutant?
- Healthy adults
- Individuals with chronic lung disease
- Asthmatics
33
What are the effects of sulfur dioxide on healthy adults?
Increased respiratory symptoms
34
What are the effects of sulfur dioxide on individuals with chronic lung disease?
Increased mortality
35
What are the effects of sulfur dioxide on Asthmatics
- Increased hospitalization
| - Decreased lung function
36
What are some outdoor air pollutants?
- Ozone
- Sulfur dioxide
- Particulate matter (soot)
- Carbon monoxide
37
Ozone:
• Ground level Ozone toxicity is largely mediated free radicals, which injure ?, releasing inflammatory mediators → mild sx (decreased lung function & chest discomfort)
- Exposure more dangerous for people with ? or ?
• respiratory tract epithelial cells and type I alveolar cells
- Asthma or emphysema
38
Sulfur Dioxide:
• Combines with ? and ?
- Produced by ? burning fossil fuels, copper smelting, and byproduct of paper mills
- Sulfuric acid and sulfuric trioxide burning sensation nose & throat, ?, and ? in those susceptible
• Ozone and particulate matter
- power plants
- difficulty breathing
- asthma attacks
39
```
Particulate matter (soot):
• ? and ?
```
- fine or ultrafine particles less than ? µm in diameter are the most harmful; readily
inhaled into the alveoli, releasing a number of inflammatory mediators
- greater than ? µm in diameter removed in the nose, or trapped by the mucociliary
epithelium of the airways
• Pulmonary inflammation & secondary cardiovascular
effects
- 10
- 10
40
Carbon Monoxide
• nonirritating, colorless, tasteless, odorless gas produced when there is incomplete oxidation of ?
- ? : working in tunnels, underground garages, and in highway toll booths with high exposures to automobile fumes
- ? : In a small, closed garage, the average running car can produce sufficient CO
to induce coma or death within ? minutes, and CO concentrations can also rapidly rise to toxic levels with improper use of gasoline-powered generators (e.g., during power outages)
or following mine fires
• hydrocarbons
- Chronic poisoning
- Acute toxicity
- 5
41
• CO kills by inducing CNS depression; widespread ? changes
- What are areas of brain affected?
- If death occurs rapidly, NO morphologic changes; longer survival the brain may be slightly ?, with ? hemorrhages and ? neuronal changes
- If pt recovers, they still can have ?, ?, and ?
• ischemic
- Basal ganglia & lenticular nuclei
- edematous
- punctate
- hypoxia-induced
- impaired memory, vision, hearing and speech
42
Hemoglobin has ?-fold greater affinity for CO than for oxygen
200
43
Systemic hypoxia: Hb = ? to ? saturated with CO
20% to 30%
44
Unconsciousness and death ~60% to 70% saturation,
5
45
Hallmark of CO
generalized cherry-red color of the skin and mucous membranes
46
Pollutants associated with indoor air pollution
- Wood smoke
- Bioaerosols
- Radon
- Formaldehyde
- Sick building syndrome
47
Indoor Air Pollution:
| polycyclic hydrocarbons are carcinogens
Wood smoke
48
Indoor Air Pollution:
| Legionnaires Dz, viral pneumonia, pet dander, fungi, molds
Bioaerosols
49
Indoor Air Pollution:
radioactive gas derived from uranium; Increased lung
cancer risk
Radon
50
Indoor Air Pollution:
| Building materials, poorly ventilated trailers following disasters; carcinogen
Formaldehyde
51
Indoor Air Pollution:
Indoor pollutants, poor
ventilation
Sick building syndrome
52
Readily absorbed metal that binds to sulfhydryl groups in proteins and interferes with calcium metabolism, effects that lead to ?, ?, ?, ?, and ? toxicities
Lead
- hematologic, skeletal, neurologic, gastrointestinal, and renal toxicities
53
Lead:
- ? contamination for kids
- Occupational exposure: ?
- Most of the absorbed lead (80% - 85%) incorporated into ?, competes with calcium; t1/2 in bone = 20-30 years
- Flaking lead paint and soil
- battery manufacturing, pigments, car radiators, & tin cans
- bone and developing teeth *
54
Lead:
• Low level Pb: subtle deficits in intellect, behavioral problems, hyperactivity, poor organizational skills in ?; ? damage!!
- sensory, motor, intellectual, & psychologic impairments, including decreased IQ, learning disabilities, retarded
psychomotor development, blindness; in more severe cases, ?
- Pb toxicity in mother may impair ? development in prenatal infant
• kids ; brain
- psychoses, seizures, & coma
- brain
55
Lead:
• CNS disturbances: ? peripheral neuropathies
- ? muscles of the wrist and fingers often first (wrist-drop), followed by paralysis of the ? muscles (foot-drop)
• adults
- extensor
- peroneal
56
Lead:
Radiodense deposits in metaphyses (interferes with remodeling of cartilage); also in the gums
Lead lines
57
Lead:
- Pb --> heme def --> ?, ?, and ? (iron-laden mitochondria)
hypochromic microcytic anemia, basophilic stippling, and ring sideroblasts
58
Lead:
extremely severe , poorly localized abdominal pain
Lead "colic"
59
Lead:
- Renal: proximal tubule damage; chronic damage = ?
interstitial fibrosis & possible renal failure
60
Lead poisoning effects in bones of children?
Radiodense deposits in epiphyses
61
Nonoccupational ways to get lead poisoning?
- Water supply
- Paint dust and flakes
- Automotive exhaust
- Urban soil
62
Anemia: Microcytic, hypochromic
- MCV < ? fL
- MCH < ? pg
- What is in this category?
- 80
- 27
- Lead poisoning
63
Metals:
Binds to sulfhydryl groups, damage CNS (developing brain) & kidney
Mercury
64
Mercury:
- Main sources:
- ? disease: cerebral palsy, deafness, blindness, mental retardation, & major CNS defects in children exposed in utero
- contaminated fish (methyl mercury), mercury vapors from metallic mercury in
dental amalgams
- Minamata
65
Metal:
Interfere with cellular metabolism, --> toxicities most prominent in the GI
tract, nervous system, skin & heart (Borgia & Medici poisonings)
Arsenic
66
Arsenic:
- In soil & water naturally; wood preservatives, herbicides, herbal medicines, …
- Large quantities ingested --> ?, ? and ? toxicities
- 2-8 wks post exposure: ? neuropathy; ?, ?, ?
- Chronic skin changes: ? and ?
• Increased risk for cancers of lungs, bladder, and skin (multiple on ? and ?)
- GI, cardiovascular and CNS toxicities
- sensorimotor neuropathy; parathesias, numbness, pain
- hyperpigmentation and hyperkeratosis
- palms and soles
67
Metal:
preferentially toxic to kidneys and lungs, via uncertain mechanisms that may involve increase ROS; source: nickel-cadmium batteries, soil, plants = ?
Cadmium
- food
68
Cadmium
- Obstructive lung dz, ? damage, skeletal abn assoc with ?
- ?(ouch-ouch): Japan; osteoporosis & osteomalacia with renal dz
- Increased risk of ? cancer (living near zinc smelters)
- renal tubular
- calcium loss
- “Itai-Itai”
- lung
69
7 Occupational Health Risks
1. Organic solvents (chloroform and carbon tetrachloride)
2. Polycyclic Hydrocarbons
3. Organochlorides
4. Dioxins and PCBs
5. Mineral Dusts
6. Vinyl Chloride
7. Bisphenol A (BPA)
70
Organic Solvents: (chloroform and carbon tetrachloride in degreasing and dry cleaning agents and paint removers)
- Acute exposure to high levels of vapors leads to ? --> ?. Lower levels are toxic for ? and ?
- Occupational exposure of rubber workers to ? and ? --> risk of ?
- Dose-dependent ? and increased risk of ?
- Dizziness and confusion --> CNS depression and coma
- Lower levels are toxic for liver and kidneys
- BENZENE AND 1,3-BUTADIENE
- leukemia
- Dose-dependent MARROW APLASIA and increased risk of ACUTE MYELOID LEUKEMIA (AML)
71
Polycyclic hydrocarbons: combustion of fossil fuels; scrotal cancers in chimney sweeps
- Among the most potent carcinogens
- Which diseases associated ?
Lung and bladder cancer
72
Organochlorines: synthetic lipophilic products that resist degradation; Important
organochlorines used as pesticides include ?. Nonpesticide organochlorines include polychlorinated biphenyls (?) and ?
- Disrupt ? because of antiestrogenic or antiandrogenic activity
- DDT
- PCBs and dioxin
- Hormonal balance
73
Dioxins and PCBs: folliculitis and a dermatosis = ? characterized by acne, cyst formation, hyperpigmentation & hyperkeratosis, face & behind ears
- Abnormalities in the ? and ?
- Chloracne
| - Liver and CNS
74
Mineral dusts: coal dust, silica, asbestos, beryllium --> ?
- Asbestosis (workers and family members) --> ?
- ? : asbestos fibers coated in iron
- Pneumonconioses
- Mesothelioma; black lung
- Ferruginous bodies
75
Vinyl Chloride
- Leads to what disease ?
Angiosarcomas in liver
76
BPA: line almost all food bottles and cans
- potential ? disruptor (infants who drink from BPA-containing containers may be particularly susceptible to its effects)
- endocrine
77
90% of lung cancers are due to ?
Tobacco
78
Tobacco decreases overall survival through dose-dependent effects expressed as ? = average number of cigarette packs smoked/day X # years of smoking
pack-years
79
- Cessation of smoking greatly decreases, within 5 years, overall mortality and risk of death from ? diseases.
- Lung cancer mortality decreases 21% within 5 years, but the excess risk persists for ? years.
- cardiovascular
| - 30
80
An alkaloid present in tobacco leaves, is not a direct cause of tobacco-related diseases, but is strongly addictive
Nicotine
81
Adverse effects of smoking?
- Cancer of oral cavity
- Cancer of larynx
- Cancer of esophagus
- Cancer of lung
- Chronic bronchitis, emphysema
- Myocardial infarction
- Peptic ulcer
- Cancer of pancreas
- Systemic atherosclerosis
- Cancer of bladder
82
Effects of Tobacco Smoke Constituents:
- Tar = ?
- Polycyclic aromatic hydrocarbons = ?
- Nicotine = ?
- Phenol = ?
- Benzoapyrene = ?
- Carbon monoxide = ?
- Formaldehyde = ?
- Nitrogen oxides = ?
- Nitrosamine = ?
- Tar = Carcinogenesis
- Polycyclic aromatic hydrocarbons = Carcinogenesis
- Nicotine = Ganglionic stimulation and depression; tumor promotion
- Phenol = Tumor promotion; mucosal irritation
- Benzoapyrene = Carcinogenesis
- Carbon monoxide = Impaired oxygen transport and utilization
- Formaldehyde = Toxicity to cilia; mucosal irritation
- Nitrogen oxides = Toxicity to cilia; mucosal irritation
- Nitrosamine = Carcinogenesis
83
Tobacco:
• Agents in smoke have a direct irritant effect on the tracheobronchial
mucosa, --> ? and increased ? production (bronchitis)
- Inflammation
| - Mucus
84
Tobacco:
• Cigarette smoke causes the recruitment of leukocytes to the lung, with increased local elastase production & subsequent injury to lung tissue, leading to ?
emphysema
85
Tobacco:
• polycyclic hydrocarbons and nitrosamines, potent carcinogens directly involved in the development of ? cancer
- ten-fold higher incidence of lung carcinomas in ? workers and ? miners
- Multiplicative interaction: tobacco & alcohol --> ? and ?cancers
• lung cancer
- asbestos
- uranium
- laryngeal and oral cancer
86
Tobacco
- ? facilitate the excretion
carcinogens; however, some intermediates are electrophilic and form DNA adducts that can cause mutations in oncogenes & tumor suppressors
CYPs
87
• Cigarette smoking is associated with cancers of the ?
• Most common diseases caused by cigarette smoking involve the lung and
include ?
• esophagus, pancreas,
bladder, kidney, cervix & bone marrow
• emphysema, chronic bronchitis, and chronic obstructive pulmonary
disease (COPD)
88
• Cigarette smoking is also strongly linked to the development of ? and its major complication, ?
- Multiplicative effect on MIs when combine smoking with ? and ?
- 30,000 - 60,000 cardiac deaths in the US yearly assoc with ? smoke exposure
* atherosclerosis
* myocardial infarction
- HTN and hypercholesterolemia
- passive
89
Maternal smoking increases the risk of ?
spontaneous abortions, preterm
| births and intrauterine growth retardation (IUGR)
90
• Passive smoke inhalation = environmental tobacco smoke
- ? X increased risk of ? cancer in nonsmoker exposed vs unexposed nonsmoker
- Increased risk of coronary atherosclerosis (CAD) and fatal MI
- Increased risk of ? and other respiratory illness in ? exposed in the home
- 1.3 X
- lung cancer
- asthma
- children
91
The risk of lung cancer is determined by the number of ?
cigarettes smoked
92
Multiplicative increase in the risk of ? cancer from the interaction between CIGARETTE smoking and ALCOHOL consumption
- laryngeal
93
Measured at age 75, the difference in survival between smokers and nonsmokers is ? years
7.5 years
94
Which country is the world's largest producer and consumer of cigarettes?
China
95
* > 10 million chronic alcoholics in US; alcohol responsible > ? deaths annually
* > 50% of these deaths: ?, and alcohol-related ? and ?
- About 15,000 annual deaths due to ?
* 100,000
* > 50% of these deaths: DRUNKEN DRIVING, and alcohol-related HOMICIDES and SUICIDES
- cirrhosis of the liver
96
What is the legal definition of drunk driving in the US?
- In an average person, this amount can be reached after consumption of how many standard drinks?
80 mg/dL in the blood
- 3 standard drinks (3 beers, 15 oz of wine, or 4-5 oz of 80 proof distilled spirits)
97
What are the alcohol amounts in the blood for:
- Drowsiness = ?
- Stupor = ?
- Coma (possible respiratory arrest) = ?
- Drowsiness = 200 mg/dL
- Stupor = 300 mg/dL
- Coma (possible respiratory arrest) = >300 mg/dL
98
Most of the alcohol in the blood is oxidized to acetaldehyde in the
liver by ?
alcohol dehydrogenase (ADH)
99
Acetaldehyde produced by alcohol metabolism is converted
to acetate by ?, which is then utilized in the mitochondrial
respiratory chain
ADH
100
Induction of CYPs by alcohol explains the increased susceptibility of alcoholics to other compounds metabolized by the same enzyme
system, which include ?
drugs, anesthetics, carcinogens, and industrial
| solvents
101
EtOH in high concentration competes with other CYP2E1 substrates and delays drug catabolism, potentiating the ? effects of narcotic, sedative, and psychoactive drugs in the CNS
depressant
102
Metabolism of Ethanol:
- Oxidation of ETHANOL to ACETALDEHYDE by 3 different routes (?, ?, ?) and the generation of acetic acid
- Oxidation by ADH takes place in the ?
- The cytochrome P-450 system and its CYP2E1 isoform are located in the endoplasmic reticulum (?)
- Catalase is located in the ?
- Oxidation of acetylaldehyde by ALDH (aldehyde dehydrogenase) occurs in ?
- ? oxidation is the most important route
- Catalase is involved in only ?% of Ethanol metabolism
- Oxidation through CYPs may also generate ?
- Oxidation of ethanol to acetaldehyde by 3 different routes (MICROSOMES, CYTOSOL, PEROXISOMES) and the generation of acetic acid
- Cytosol
- microsomes
- Peroxisomes
- mitochondria
- ADH
- 5%
- reactive oxygen species
103
Metabolism of Ethanol:
High alcohol concentrations ? metabolisms of other compounds (ie drugs by CYP2E1)
inhibit
104
Metabolism of Ethanol:
Increased NADH associated with increased ? levels and ? (due to low NAD)
- lactic acid
| - steatosis
105
What are the effects of acute alcoholism?
mostly CNS effects (depressant), but also hepatic steatosis (fatty liver), acute gastritis and ulceration
- Reversible if EtOH consumption discontinued
106
Chronic alcoholism effects?
Shortened life span due to damage of the liver, GI tract, CNS, cardiovascular system, & pancreas
107
Organs and tissue involved in chronic alcoholism?
- Liver (main site of chronic injury)
- GI
- Thiamine (vit B1)
- Alcoholic cardiomyopathy
- Acute and chronic pancreatitis
- Fetal alcohol syndrome
- Incidence of cancer
- Malnutrition and nutritional deficit
108
Organs and tissue involved in chronic alcoholism and their effects:
1. Liver = ?
- Cirrhosis assoc with portal hypertension and increased risk for hepatocellular carcinoma
2. GI = ?
3. Thiamine (vit B1) = ?
4. Alcoholic cardiomyopathy = ?
- Heavy EtOH use assoc with liver injury --> decreased ? --> increased likelihood coronary heart dz
5. Acute and chronic pancreatitis
6. Fetal alcohol syndrome = ?
7. Incidence of cancer = ?
8. Malnutrition & nutritional def (esp ?)
1. Liver = steatosis, alcoholic hepatitis, & cirrhosis
- Cirrhosis assoc with PORTAL HYPERTENSION and increased risk for HEPATOCELLULAR CARCINOMA
2. GI = bleeding from gastritis, gastric ulcer, or esophageal varices (assoc with cirrhosis)
3. Thiamine (vit B1) = PERIPHERAL NEUROPATHIES and WERNICKE-KORSAKOFF SYNDROME; cerebral
atrophy, cerebellar degeneration, & optic neuropathy
4. Alcoholic cardiomyopathy = DILATED CONGESTIVE CARDIOMYOPATHY, hypertension
- Heavy EtOH use assoc with liver injury --> decreased HDL --> increased likelihood coronary heart dz
6. Fetal alcohol syndrome = MICROCEPHALY, GROWTH RETARDATION, and FACIAL ANOMALIES in newborn;
DECREASED MENTAL FUNCTIONS as child grows; first trimester most harmful
7. Incidence of cancer = oral cavity, esophagus, liver, +/- breast in women
8. Malnutrition & nutritional def (esp vit B)
109
How is alcohol linked to hypothermia?
- Can increase the chances of hypothermia (so be careful of drinking it in the cold!)
- Alcohol may make your body feel warm inside, but it causes your blood vessels to expand, resulting in more rapid heat loss from the surface of your skin. The body's natural shivering response is diminished in people who've been drinking alcohol
110
Moderate amounts of alcohol (20-30 gm/d) increase ?, inhibit ? aggregation, decrease ? levels possibly protecting against ?
- HDL
- platelet
- fibrinogen
- coronary heart disease
111
Common drug reactions and their agents:
Reaction for Bone Marrow and blood cells: (what are their offenders?)
1. Granulocytopenia, aplastic anemia, pancytopenia
2. Hemolytic anemia, thrombocytopenia
Offenders
1. ANTINEOPLASTIC AGENTS, immunosuppressives, chloramphenicol
2. Penicillin, heparin, methyldopa, quinidine
112
Therapeutic Drugs:
Untoward effects of drugs that are given in conventional therapeutic settings?
- Example?
Adverse drug reactions
- (ex. discoloration of the skin caused by antibiotic minocycline)
113
Drug-induced hypersensitivity
reactions most commonly present as?
(ex. ?)
Skin rashes
- Ex. drug metabolite/iron/melanin pigment particles
114
Therapeutic Drugs:
| Anticoagulants
• warfarin (vit K antagonist) and dabigatran (inhibits thrombin)
- Bleeding; thrombosis due to insufficient dosage (ie stroke)
115
Therapeutic Drugs:
| Menopausal hormone therapy (MHT)
Formerly hormone replacement
therapy (HRT): estrogens with progestogen (OK in early menopause, but not long term)
- Estrogen-progesterone increases the risk of breast cancer after about 5-6 years but estrogen alone in women with hysterectomy is associated with reduction in risk of breast cancer
- Can be protective against atherosclerosis and coronary disease in women younger than 60 but not in women who started at an older age
- Increases the risk of stroke and venous thromboembolism
116
Therapeutic Drugs:
Oral Contraceptives
- What condition is associated with it?
- Don't increase breast cancer risk
- Increase risk cervical cancer; esp +HPV, 3-6X increase risk venous thrombosis and PE
- Doesn't increase CAD in women <30yo, but 2X increase smokers >35yo
- HEPATIC ADENOMA – (rare and benign) can happen in older pt with prolong OC use
117
Therapeutic Drugs:
Anabolic Steroids
stunted growth, acne, gynecomastia, testicular atrophy; facial hair & menstrual changes in females; psychiatric issues
- Increased risk MI
118
Therapeutic Drugs:
Acetaminophen
- US 50% unintentional OD
- US 50% of acute liver failures
with 30% mortality
- CENTRILOBULAR NECROSIS
119
Therapeutic Drugs:
| Aspirin
- ACUTE salicylate poisoning effects the brain --> nausea --> coma
- CHRONIC (salicylism) HA, dizziness, tinnitus, bleeding, coma
- ANALGESIC NEPHROPATHY (caused by a mix of aspirin and acetaminophen when taken over many years can cause tubulointerstitial nephritis with renal papillary necrosis)
120
Acetaminophen Metabolism and Toxicity
- 95% of Acetaminophen goes down one route and 5% down another
- What happens down the 95% route ?
- What happens down the 5% route
95%
1. Detoxification by Phase II enzymes
2. Excretion in urine as glucuronate or sulfate conjugates
5%
1. CYP2E1 activity
2. NAPQ
- Normally conjugated with GSH and you get no toxicity
- BUT when acetaminophen is taken in large doses, unconjugated NAPQ accumulates and causes hepatocellular injury leading to centrilobular necrosis that can progress to liver failure:
1. Protein adducts; Lipid peroxidation
2. Hepatocyte necrosis; Liver failure
121
Chronic toxicity of large doses of aspirin can lead to ?
- gastric ulceration
| - bleeding
122
Drugs of Abuse and their Street Names
- Opiates
- Methamphetamine (aka speed, meth)
- MDMA (aka Ecstasy)
- Marijuana
- Huffing/glue sniffing
- Bath salts
123
Clinical Presentation of Drugs of Abuse:
Opiates
- Infections:
Profound respiratory depression, arrhythmia, cardiac arrest, and pulmonary edema; sudden death unrelated to OD
- Infections: 10% endocarditis right heart valves; subQ, liver, lungs
124
Clinical Presentation of Drugs of Abuse:
| Methamphetamine (aka speed, meth)
```
violent behavior, confusion,
psychotic sx (paranoia, hallucinations)
```
125
Clinical Presentation of Drugs of Abuse:
| MDMA
often spiked with other drugs which can enhance its effects on CNS
126
Clinical Presentation of Drugs of Abuse:
| Marijuana
Increased HR, +/- BP which may cause angina in pt with CAD
- cognitive and psychomotor impairment with continued use
- large # carcinogens in
smoke
127
Clinical Presentation of Drugs of Abuse:
| Huffing/glue sniffing
MRI-detectable brain damage that ranges from mild-
| severe dementia
128
Clinical Presentation of Drugs of Abuse:
| Bath salts
agitation, psychosis, MI, and suicide
129
Common Drugs of Abuse:
- Class: Sedative-hypnotics
- Molecular Target: ?
- Example: ?
- Molecular Target: GABAa receptor (agonist)
- Example:
1. Barbiturates
2. Ethanol
3. Methaqualone (Quaalude)
4. Glutethimide (Doriden)
5. Ethchlorvynol (Placidyl)
130
Common Drugs of Abuse:
- Class: Opioid Narcotics
- Molecular Target: ?
- Example: ?
- Molecular Target: Mu opioid receptor (agonist)
- Example:
1. Heroin, Hydromorphone (Dilaudid)
2. Oxycodone (OxyContin)
3. Methadone (Dolophine)
4. Meperidine (Demerol)
131
Common Drugs of Abuse:
- Class: Psychomotor Stimulants
- Molecular Target:
1.
2.
- Example: ?
- Molecular Target:
1. Dopamine transporter (antagonist)
- Example: Cocaine
2. Serotonin receptors (toxicity)
- Example:
~ Amphetamines
~3,4methylenedioxymethamphetamine (MDMA, ecstasy)
132
Common Drugs of Abuse:
- Class: Phencyclidine- like drugs
- Molecular Target: ?
- Example: ?
- Molecular Target: NMDA glutamate receptor channel (antagonist)
- Example:
1. Phencyclidine (PCP, angel dust)
2. Ketamine
133
Common Drugs of Abuse:
- Class: Cannabinoids
- Molecular Target: ?
- Example: ?
- Molecular Target: CBI cannabinoid receptors (agonist)
- Example:
1. Marijuana
2. Hashish
134
Common Drugs of Abuse:
- Class: Hallucinogens
- Molecular Target: ?
- Example: ?
- Molecular Target: Serotonin 5-HT 2 receptors (agonist)
- Example:
1. Lysergic acid diethylamide (LSD)
2. Mescaline
3. Psilocybin
135
Cocaine Effects on Neurotransmission:
• coronary artery vasoconstriction+ plt
aggregation + thrombus formation --> ?
* lethal arrhythmias (not dose related)
* Decreased Blood flow to placenta --> ? and ?
* Hyperpyrexia and seizures
TACHYCARDIA, HTN, AND PERIPHERAL VASOCONSTRICTION
- myocardial ischemia
- fetal hypoxia and spontaneous abortion
136
Clinical significance of burn injury depends on: ?
* Depth of burn
* % of body surface covered by burn
* Internal injuries: inhalation of toxic fumes and heat
* TX: fluid & electrolyte management, and infection control
137
Burn Classification
* 1st degree= superficial; epidermis only
* 2nd degree= partial thickness; epidermis and dermis
* 3rd degree= full thickness; extend into the subcutaneous tissue
138
Complication of burns involving >20% of body surface?
Rapid shift of body fluids into
interstitial compartment --> SHOCK
- Generalized edema, including pulmonary edema, can be severe
- Hypermetabolic state: excess heat loss and increased need for nutritional support
139
virtually all burns colonized: Pseudomonas aeruginosa, MRSA, Candida
Sepsis
140
Within 24-48 hrs, direct heat effects on upper airway (mouth, nose, trachea..), and inhalation of noxious gases (Cl, sulfur dioxide, ammonia….)
Respiratory insufficiency
141
original burn and site of donor graft; excessive collagen deposition
Hypertrophic scars
142
Hyperthermia: heat stroke = ?
- Malignant hyperthermia: “heat-stroke-like” rise in core body temp and muscle contractors in response to common ?; RYR1 gene
lack of sweating
- ANESTHETICS
143
Hypothermia: body temp <90F leads to ?
loss of consciousness, bradycardia, then atrial fibrillation
144
Electrical injury: two types of injuries
* Burns
* Ventricular fibrillation or cardiac-respiratory failure
* Lightening classic high-voltage electrical injury
145
Effects of ionizing radiation on DNA and its consequences:
3 Radiation units: ?
- Curie (Ci): radiation emitted
- Gray (Gy): energy absorbed
- Sievert (Sv): the equivalent dose (expressed in Sieverts ) corresponds to the absorbed dose (expressed in Grays) multiplied by the relative biologic effectiveness of the radiation
146
Effects of ionizing radiation on DNA and its consequences:
Determinants of effect: ?
1. Rate of delivery
2. Field size
3. Cell proliferation
4. O2 effects and hypoxia
5. Vascular damage
147
Morphology of ionizing radiation: ?
* endothelial cell proliferation, collagenous hyalinization and thickening of the intima are seen in irradiated vessels, --> marked ? or even ? of the vascular lumens
* Increased interstitial collagen in the irradiated field usually becomes evident, --> ? and ?
• Histologic constellation of cellular pleomorphism, giant-cell formation, conformational
changes in nuclei, and abnormal mitotic figures creates a more than passing similarity between ? and ?, a problem that plagues the pathologist when evaluating irradiated tissues for the possible persistence of tumor cells
Nuclear swelling, giant cells, pleomorphic nuclei, >1 nucleus,
cytoplasmic swelling, ...
- NARROWING or even OBLITERATION of the vascular lumens
- scarring and contractions
- radiation-injured cells and cancer cells
148
Cancer Risks:
- from radiation exposure: Increased incidence of ? and ? in several organs (e.g., thyroid, breast, and lungs) in survivors of the atomic bombings of Hiroshima and Nagasaki
- leukemias and solid tumors
149
Cancer Risks
- ? cancers in survivors of the Chernobyl accident
Thyroid cancers
150
Cancer Risks:
- ? tumors, and increased frequency of ? and ?, in inhabitants of the Marshall Islands exposed to nuclear fallout
- Thyroid tumors
| - Leukemias and birth defects
151
Cancer risks:
- The development of “second cancers”, such as ?, ?, and ? in individuals who received
radiation therapy for cancers such as Hodgkin lymphoma
acute myeloid leukemia, myelodysplastic syndrome, and solid tumors
152
Main Organs affected by Radiation and Major Morphological Changes
1. Lungs
- Edema
- ARDS
- Interstitial fibrosis (months to years) *
2. GI Tract
- Mucosal injury (early)
- Ulceration (early)
- Fibrosis of wall (late) *
```
3. Gonads
Early:
A. Testis (destruction)
- Spermatogonia
- Spermatids
- Sperm
B. Ovaries (destruction)
- Germ cells
- Granulosa cells
```
C. Atrophy and fibrosis of gonads (late) *
153
Doses for Acute Radiation Effects on Specific Organs:
Testes
- Health Effect: ?
- Dose: ?
- Health Effect: Temporary sterility
| - Dose: 0.15
154
Doses for Acute Radiation Effects on Specific Organs:
Bone Marrow
- Health Effect: ?
- Dose: ?
- Health Effect: Depression of hematopoiesis
| - Dose: 0.50
155
Doses for Acute Radiation Effects on Specific Organs:
Skin
- Health Effect: ?
- Dose: ?
- Health Effect: Reversible skin effects (e.g., erythema)
| - Dose: 1-2
156
Doses for Acute Radiation Effects on Specific Organs:
Ovaries
- Health Effect: ?
- Dose: ?
- Health Effect: Permanent sterility
| - Dose: 2.5-6
157
Doses for Acute Radiation Effects on Specific Organs:
Skin
- Health Effect: ?
- Dose: ?
- Health Effect: Temporary hair loss
| - Dose: 3-5
158
Doses for Acute Radiation Effects on Specific Organs:
Testis
- Health Effect: ?
- Dose: ?
- Health Effect: Permanent sterility
| - Dose: 3.5
159
Doses for Acute Radiation Effects on Specific Organs:
Lens of eye
- Health Effect: ?
- Dose: ?
- Health Effect: Cataract
| - Dose: 5
160
```
Effects of Total Body Ionizing Radiation:
Main Site of Injury
- 0-1 Sv = ?
- 1-2 Sv = ?
- 2-10 Sv = ?
- 10-20 Sv = ?
- >50 Sv = ?
```
- 0-1 Sv = None
- 1-2 Sv = Lymphocytes
- 2-10 Sv = Bone Marrow
- 10-20 Sv = Small bowel
- >50 Sv = BRAIN
161
```
Effects of Total Body Ionizing Radiation:
Main signs and symptoms
- 0-1 Sv = ?
- 1-2 Sv = ?
- 2-10 Sv = ?
- 10-20 Sv = ?
- >50 Sv = ?
```
- 0-1 Sv = None
- 1-2 Sv = Moderate granulocytopen ia Lymphopenia
- 2-10 Sv = Leukopenia, hemorrhage, hair loss, vomiting
- 10-20 Sv = Diarrhea, fever, electrolyte imbalance, vomiting
- >50 Sv = Ataxia, coma, convulsions, vomiting
162
```
Effects of Total Body Ionizing Radiation:
Time of development
- 0-1 Sv = ?
- 1-2 Sv = ?
- 2-10 Sv = ?
- 10-20 Sv = ?
- >50 Sv = ?
```
- 0-1 Sv = -
- 1-2 Sv = 1 day to 1 week
- 2-10 Sv = 2-6 weeks
- 10-20 Sv = 5-14 days
- >50 Sv = 1-4 hours
163
```
Effects of Total Body Ionizing Radiation:
Lethality
- 0-1 Sv = ?
- 1-2 Sv = ?
- 2-10 Sv = ?
- 10-20 Sv = ?
- >50 Sv = ?
```
- 0-1 Sv = None
- 1-2 Sv = None
- 2-10 Sv = Variable (0% to 80%)
- 10-20 Sv = 100%
- >50 Sv = 100%
164
Malnutrition:
- Leads to ?
- Obesity leads to ?
- loss of fat and muscle tissue, weight loss, lethargy, and generalized weakness
- Obesity = diabetes, atherosclerosis, and cancer
165
Dietary Insufficiency
- Primary = ?
- Secondary = ?
- Primary = missing from diet
| - Secondary = malabsorption, impaired utilization or storage, excess loss, or increased need
166
Causes of dietary insufficiency?
Poverty, infections, acute & chronic illnesses, chronic alcoholism, ignorance, self-imposed dietary restrictions, GI diseases and malabsorption syndromes
167
Causes 50% deaths in infancy and childhood in DEVELOPING countries; older & debilitated patients in nursing homes & hospitals?
Protein- energy malnutrition (PEM)
168
Protein- energy malnutrition:
- Estimated > ?% of older residents in ? in the US are malnourished. Weight loss of more than 5% associated with PEM increased mortality in nursing home patients ~5X
- 50%
| - nursing homes
169
Protein- energy malnutrition:
- Signs of secondary PEM include 3 things?
1. DEPLETION OF SUBCUTANEOUS FAT IN the arms, chest wall,
shoulders, or metacarpal regions
2. WASTING of the quadriceps and deltoid muscles
3. ankle or sacral EDEMA
170
Protein- energy malnutrition:
Bedridden or hospitalized malnourished patients increase risk of ?
infection, sepsis, impaired wound healing, & death after surgery
171
Malnutrition:
Which disease involves wt <60% NL for sex, ht and age; growth retardation & muscle loss?
- SERUM ALBUMIN NL; anemia; immune deficiency
- Muscle proteins and subQ fat used as fuel --> EMACIATED EXTREMITIES
- Bone marrow may be hypoplastic
Marasmus
172
Which disease involves decreased protein more severe > decrease in total calories?
• HYPOALBUMINEMIA --> generalized or dependent EDEMA; vit def, immune def &
secondary infections
* Depletion of visceral protein compartment; FATTY LIVER; sparing of subQ fat & muscle
* Weaned too early, & fed carbohydrate diet (Ghana & Southeast Asia)
• Chronic diarrhea, protein losing enteropathies, nephrotic syndrome, extensive
burns, fad diets or replacement of milk with rice-based beverages
* Small bowel shows a decrease in the crypts of the glands
* Bone marrow may be hypoplastic
Kwashiorkor
173
What condition causes PEM complication in AIDS or advanced cancers?
- 50% of cancer pts; GI, pancreatic and lung cancers
- Extreme wt loss, fatigue, muscle atrophy, anemia, anorexia, and edema
- Mortality from atrophy of the diaphragm and other respiratory muscles
Cachexia
174
Mechanism of Cancer Cachexia:
- Proteolysis- inducing factor (PIF) produced by tumors and TNF and other cytokines produced by host immune cells activate ? and initiate the transcription of the muscle specific ?
- These ligases in turn ubiquitinate structural components of myofibrils such as ?, leading to their degradation by the proteasome
- Results in loss of ?
- NF-kB
- ubiquitin ligases
- myosin heavy chain
- myofibrils and loss of muscle mass
175
Which disease involves self-induced starvation leading to marked wt loss?
- Highest death rate of any psychiatric DO
- Amenorrhea, decreased thyroid hormone, decreased bone density
Anorexia Nervosa
176
Which disease involves binge/purge
Bulimia (more common than anorexia and better prognosis)
177
Clinical affects of Bulimia?
* Electrolyte imbalance (hypokalemia) --> cardiac arrhythmia
* Pulmonary aspiration of gastric contents
* Esophageal & gastric rupture
178
Complication of BOTH bulimia and anorexia?
Susceptibility to cardiac arrhythmia and sudden
| death due to hypokalemia
179
Vitamin associated with maintenance of normal vision, regulation of cell growth and differentiation and regulation of lipid metabolism
Vitamin A (retinol)
180
Vitamin A:
Functions:
1.
2.
3.
Deficiency Syndromes:
1. ?
2. ?
3. ?
Functions:
1. Component of visual pigment
2. Maintenance of specialized epithelia
3. Maintenance of resistance to infection
Deficiency Syndromes:
1. Night blindness, xerophthalmia, blindness, BITOT SPOTS
2. Epithelial/Squamous metaplasia and keratinization
3. Vulnerability to infection, particularly measles
181
Vitamin A Metabolism
Source (meats, veggies) --> Intestinal cell --> Transport to Liver (Retinol in chylomicrons)
--> Liver storage (Retinyl esters) --> Transport to tissues (Retinol binding protein) --> Peripheral tissues (Retinol oxidized to Retinoic acid)
182
Function of Vitamin D?
Maintenance of adequate plasma levels of CALCIUM and PHOSPHORUS to support metabolic functions, bone mineralization and neuromuscular transmission
183
Vitamin D is required for the prevent of:
- ? IN KIDS
- ? IN ADULTS
- ?
- Rickets (in children whose
epiphyses have not already closed)
- Osteomalacia (in adults)
- Hypocalcemic tetany (a convulsive state caused by an insufficient extracellular concentration of ionized calcium, required for relaxation of muscles)
184
Vitamin D:
Signs of Rickets?
frontal bossing, squared head, rachitic rosary, pigeon breast deformity, lumbar lordosis, bowing of the legs
185
Vitamin D
Disease associated with inadequate mineralization of bone, weak and prone to fracture?
Osteomalacia
186
Immune response of Vitamin D?
Helps clear Mycobacterium tuberculosis infections
187
Vitamin D Metabolism:
The major source of vitamin D for humans is its ? from a precursor, 7-dehydrocholesterol, in a ? reaction that requires solar or artificial UV light in the range of 290 to 315 nm (UVB radiation).
- endogenous synthesis
| - photochemical
188
Vitamin D Metabolism:
- Vit D is produced from 7-dehydrocholesterol in the skin or is ingested in the diet
- It is converted in the ? into 25(OH) D, and in the ? into 1,25(OH)2D, the active form of the vitamin
- 1,25(OH)2D stimulates the expression of ?, an important regulator or osteoclast maturation and function, on osteoblasts, and enhances the intestinal absorption of calcium and phosphorus in the intestine
- Adequate calcium and phosphorus results in ?
- liver
- kidney
- RANKL
- bone mineralization, metabolic functions, and neuromuscular functions
(get issues if there is insufficient sunlight)
189
Secondary deficiency of Vitamin A with FAT MALABSORPTION is associated with ?
celiac dz, Crohn dz, colitis, Cystic fibrosis,
| bariatric surgery, mineral oil laxative
190
Functions of Vitamin C?
| Deficiency Syndrome?
- Serves in many oxidation-reduction (redox) reactions and hydroxylation of collagen
- Scurvy
191
Bone disease in growing children, HEMORRHAGES and HEALING DEFECTS in both children and adults
Scurvy
192
How to we get Vit C?
Dependent on DIET
| - Milk, some animal products (liver, fish), abundant in a variety of fruits and veggies
193
Secondary deficiency of Vit C: ?
| - Occasionally, scurvy occurs in patients undergoing ?
Older individuals who live alone and chronic alcoholics, have erratic and inadequate eating patterns
- peritoneal dialysis and hemodialysis, and among food faddists
194
Vit C deficiency causes impaired collagen formation which results in?
- Poor vessel support results in bleeding tendency (gums, skin, periosteum and joints)
- Other effects: inadequate synthesis of osteoid and impaired wound healing
195
Vitamin K
- Functions:
- Deficiency Syndromes:
- Functions: Cofactor in hepatic carboxylation of procoagulants—factors II (prothrombin), VII, IX, and X; and protein C and protein S
- Deficiency Syndromes: Bleeding diathesis
196
Vitamin B1 (thiamine)
- Functions:
- Deficiency Syndromes:
- Functions: As pyrophosphate, is coenzyme in decarboxylation reactions
- Deficiency Syndromes: Dry and wet beriberi, Wernicke syndrome, Korsakoff syndrome
197
Niacin
- Functions:
- Deficiency Syndromes:
- Functions: Incorporated into nicotinamide adenine dinucleotide (NAD) and NAD phosphate, involved in a variety of redox reactions
- Deficiency Syndromes: Pellagra—“three Ds”: dementia, dermatitis, diarrhea
198
Vitamin B6 (pyridoxine)
- Functions:
- Deficiency Syndromes:
- Functions: Derivatives serve as coenzymes in many intermediary reactions
- Deficiency Syndromes:
~ Cheilosis, glossitis, dermatitis, peripheral neuropathy
~ Maintenance of myelinization of spinal cord tracts
199
Zinc Clinical Features of Deficienc:
- Rash around eyes, mouth, nose, and anus called acrodermatitis enteropathica
- Anorexia and diarrhea
- Growth retardation in children
- Depressed mental function
- Depressed wound healing and immune response
- Impaired night vision
- Infertility
200
Iron Clinical Features of Deficiency:
Hypochromic microcytic anemia
201
Iodine Clinical Features of Deficiency:
Goiter and hypothyroidism
202
Copper Clinical Features of Deficiency:
- Muscle weakness
- Neurologic defects
- Abnormal collagen cross-linking
203
Fluoride Clinical Features of Deficiency:
Dental caries
204
Selenium Clinical Features of Deficiency:
- Myopathy
| - Cardiomyopathy (Keshan disease)
205
```
Obesity:
Excess adiposity (obesity) and excess body weight associated with ?
```
Increased incidence
| of type 2 diabetes, dyslipidemias, cardiovascular disease, HTN, & cancer
206
- Normal BMI =
- Overweight BMI =
- Obese BMI =
- Normal BMI = range is 18.5 to 25 kg/m 2
- Overweight BMI = between 25 kg/m 2 and 30 kg/m 2
- Obese BMI = greater than 30 kg/m 2
207
Fat accumulates in the trunk & abdominal cavity (mesentery & around viscera); assoc with very large increase risk for several diseases > excess accumulation of fat diffusely in subcutaneous tissue
Central, or visceral, obesity
208
Afferent System:
- Leptin comes from ?
- Function = ?
- Adipocytes
| - Function is to make you full (so if deficient in leptin = obese)
209
Afferent System:
- Insulin comes from ?
- Function = ?
- Pancreatic B cells
| - Function = Break down food (obesity = insulin resistance)
210
Afferent System:
- Ghrelin comes from?
- Function = ?
- Stomach
| - Tells you that your hungry. Feed me!! (obesity = suppression of ghrelin is reduced after meal)
211
Afferent System:
- PYY comes from ?
- Function = ?
- Intestines
| - Tells you I'm full (obese = have low PYY like in Prader Willi)
212
Role of adipocytes in chronic inflammatory states
- Adipose tissue increases the production of cytokines (TNF, IL-6, IL-1, IL-18) and chemokines in obese patients creates a chronic proinflammatory state marked by high levels of circulating C-reactive protein
- Through these mediators, adipose tissue participates in the control of energy balance and energy metabolism, functioning as a link between lipid metabolism, nutrition, and inflammatory responses
213
Consequences of Obesity:
- METABOLIC SYNDROME: ?
- Obese persons generally have hypertriglyceridemia and low HDL, both of which increase the risk of ?
- Obesity is associated with ?
- ? = 6X greater in obese than in lean subjects
- Obesity is associated with hypoventilation syndrome also called the ?
~ ?: both at night and during the day, often assoc with SLEEP APNEA, polycythemia, and eventual right-sided heart failure (COR PULMONALE)
- Marked adiposity predisposes to the development of degenerative joint disease (?)
- visceral or intra-abdominal adiposity, insulin resistance, hyperinsulinemia, glucose intolerance, HTN, hypertriglyceridemia and decreased HDL
- coronary artery disease
- nonalcoholic fatty liver disease
- Cholelithiasis (gallstones)
- pickwickian syndrome
~ Hypersomnolence
- osteoarthritis
214
Obesity and Cancer:
• Increased risk for cancers of ?
•Insulin resistance leads to ?, which has multiple effects that
may directly or indirectly contribute to cancer
- Hyperinsulinemia --> Increase in free insulin-like growth factor-1 (IGF-1); IGF-1 is a mitogen
* Obesity increases the synthesis of ?
* The ? state that is associated with obesity may itself be carcinogenic
* esophagus, pancreas, colon, rectum, breast, endometrium, kidney, thyroid and gallbladder
* hyperinsulinemia
* estrogen
* proinflammatory
215
Diet and Cancer:
Exogenous Carcinogen = AFLATOXIN which leads to what cancer ?
hepatocellular carcinoma
216
Diet and Cancer:
Endogenous Carcinogen from diet = Nitrosamines and nitrosamides which leads to what cancer?
gastric carcinomas
217
Diet and Cancer:
High animal fat and low fiber lead to what cancer?
Colon cancer
218
Total dietary fat positively correlates to which cancer?
Breast cancer
219
Vit C & E, β-carotenes and selenium seem to have ? effects due to antioxidant properties
anticarcinogenic
220
Recent studies have shown that omega-3 fatty acid supplements ? the risk of cardiovascular disease
Do NOT lower
