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137 Cards in this Set
- Front
- Back
Incidence of Occupational Injury in US
|
7,400/100,000 (4.8/100,000 fatal)
{130 million US workers at risk) |
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Highest Risk occupations
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Mining > Transportation > Agriculture > construction > public utilities#
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# of Chemical agents used in US
# pesticides # food additives # tested (% carcinogenic) |
80,000 chems in use
1500 pesticides 5500 food additives 600 tested (10% carcinogenic) |
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Types of chemical exposure
who gets ppm? who gets ppb or ppt? |
workers- ppm
general population- ppb or ppt |
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phases of toxin metabolism
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Phase I reactions- generate primary metabolites and toxic byproducts (eg benzopyrene metabolism)
Phase II reactions- involve conjucation of primary metabolite with endogenous substrate for excretion (eg methylation of mercury and bioaccumulation) |
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variation in effects of a toxin, depends on
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-Genetic variation in enzyme activity (eg glutathione in various cancers)
-Predominant metabolic pathway -Nutritional/hormonal status -Presence of other exogenous substances -Adequancy of repair pathways |
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Dose Response Curve shows:
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Response v. Dose
Threshold dose: -measureable response -permissible exposure Ceiling effect |
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Nicotine's Mechanism
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-crosses BBB
-stimulates Nicotine receptors, leading to release of Catecholamines |
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Nicotine
-crosses BBB -stimulates Nicotine receptors, leading to release of catecholamines What are the consequences? |
Increase:
HR BP CBF CO FFA mobilization ADDICTION |
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Tobacco related diseases
|
lung cancer
ischemic heart disease acute respiratory tract infections cold fetal abnormalities PUD |
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Tobacco can have synergistic effects on what other types of hazards?
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workplace hazards:
-lung cancer -bronchitis -asthma -pneumoconiosis |
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passive exposure to tobacco is associated with:
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lung cancer
ischemic heart disease AMI SIDS respiratory tract infections asthma |
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most widely used/abused drug
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ETHANOL
15-20 million alcoholics in US 100,000 deaths/ year in US |
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Acute, Chronic effects of Alcohol
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Acute = CNS depressent
Chronic = systemic, vitamin deficiencies |
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elimination of alcohol, by fraction?
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90% metabolized to acetaldehyde
rest unchanged in urine, breath, sweat |
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basis of alcohol tolerance
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induction of cytochrom p450 CYP2E1 enzyme
|
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basis for asian flush
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reduced ALDEHYDE DH in Asian population
|
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basis for lower alcohol tolerance in women
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reduced levels of alcohol DH in women
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Chronic Effects of Alcohol
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FATTY LIVER (assymptomatic acute reversible)
ACUTE ALC HEPATITIS (symptomatic reversible) LIVER CIRRHOSIS (10-15% of alcoholics) WERNICKE-KORSAKOFF SYNDROME (thyamine deficiency) DILATED CARDIOMYOPATHY ELEVATED HDL (protective) FETAL ALCOHOL SYNDROME (most common preventable cause of MR) |
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primary sites of alcohol absorption
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stomach and small intestine
|
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Main enzymes of ethanol metabolism
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ADH
ALDH CYP2E1 CATALASE |
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Fatty (alcoholic) liver
characteristics mechanism |
Asymptomatic, acute, reversible
Increased catabolism of peripheral fat Increased NADH for lipid synthesis Decreased FA oxidation in mito Decreased transport of lipoproteins from liver (microtubule dysfunction) |
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Acute (alcoholic) Hepatitis
characteristics pathology mechanism |
Symptomatic, reversible (fever, tender, jaundice)
Pathology: Necrosis, PMNs, Mallory's hyaline Mechanism = direct toxicity -Glutathione depletion -Mito injury -Altered methionine metabolism -cytokine release from Kupffer cells--> activation of more inflammatory cells -Hypoxia |
|
Liver cirrhosis
-prevalence -characteristics -symptoms -mechanism |
10-15% of alcoholics
hard, shrunken, micronodules of hepatocytes surrounded by collagen bands (laid down by ITO cells) weak, wasted, ascities, GI bleed, coma mech = DIRECT TOXIC EFFECT or CYTOKINE mediated |
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Effects of ethanol on nervous system
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Acute CNS depression
Addiciton Wernicke's snydrome (via thiamine deficiency) = ataxia, cognitive problems, opthalmoplegia, nystagmus Korsakoff syndrome = toxicity and thyamine deficiency -memory loss |
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effects of ethanol on the CV system
|
hypertension (via catecholamine release)
dilated cardiomyopathy protective effects (increased HDL, decreased platelet aggregation) |
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most common preventable cause of mental retardation
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1200/ year
FETAL ALCOHOL SYNDROME due to maternal alcohol consumption growth retardation, microcephaly, short palpebral fissures, maxillary hypoplasia, ASD ?via acetaldehyde toxicity to fetal brain? |
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Prevalence of Drug abuse in the US
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7.5 % US residents aged 15-54
|
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Risk factors for drug abuse
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family Hx
male pschiatric disorders ethanol abuse access peer pressure |
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drug associated with highest number of drug deaths in NH
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METHADONE
|
|
examples of sedative hypnotics
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ETHANOL
BARBITURATES (associated with tolerance, enzyme induction) BENZODIAZEPINES (safer) |
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Stimulants of Abuse
|
Amphetamines
Cocaine |
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Amphetamine
-Acute intoxication long term problems |
sweating, tremors, restlessness, confusion, delerium, convulsions, arrhythmias, coma, death
Fetal malformations and withdrawal MDMA toxic to serotonin neurons (depression, anxiety, panic disorder) Tolerance and withdrawal |
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Cocaine
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alkaloid extracted from Erythroxylon coca
crack = freebase cocaine Acute toxicity: rapid high of short duration chronic abuse: insomnia, anxiety, paranoia, hallucinations overdose: seizures, cardiac arrhythmias, respiratory arrest mechanism: blocks reuptake of dopamine, serotonin, catecholamines in presynaptic terminals |
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mechanism of cocaine's actions
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blocks reuptake of dopamine, serotonin, catecholamines in presynaptic terminal
|
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CV effects of cocaine
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increased BP
increased HR coronoary spasm accelearted atherosclerosis -enhanced platelet activation/aggregations -increased PAI -increased endothelial permeability |
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Opioid Narcotics
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heroin, codeine, morphine
|
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acute effects of opiod narcotics
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anxiolytic, sedation, mood changes, nausea, respiratory depression
|
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overdose of opiod narcotics
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convulsions, cardiorespiratory arrest, death
|
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problems associated with opioid narcotic abuse
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Infection (IVDA)
ski, subcutaneous, R. sided heart valves (S. aureaus tricuspid) Liver (viral hepatitis) lungs |
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Natural hallucinogens
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Mescaline (peyote)
Psilocybin (morning glory flower) Teonanacatl mushrooms Marijuana (hemp plant Cannabis sativa) |
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Chemical hallucinogens
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PCP
LSD |
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active ingredient in Marijunana
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THC
|
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effects of marijuana use
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induces relaxation, heightened sensation, impaired cognitive, motor functions
chronic use may induce lung damage (not carcinogenic) |
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what consitutes and ADVERSE DRUG REACTION
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undesired response at "therapeutic" doses
|
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frequency of Adverse Drug Reactions
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2 million hospitalized patients and 106,000 deaths/ year in the US
unpredictable, related to invidual variations in drug metabolizing enzymes |
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OC use is associated with increased risk of:
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STROKE
MI THROMOSIS/PE HPV? |
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Hormone replacement Tx is associated with increased risk of:
|
STROKE
MI THROMOSIS/PE BREAST CANCER GALLBLADDER CANCER |
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Acetominophin therapeutic dose
|
0.5gm
|
|
toxic dose of acetominophen
-symptoms |
15-25 gm (hepatic, centrilobular necrosis)
early symptoms: N/V/D/ ... shock late: jaundice, liver failure, necrosis |
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ASPIRIN
acute toxicity -dose -Cx presentation |
2-4 gm kids
10-30 gm adults Cx: respiratory alkalosis, follwed by metabolic acidosis |
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ASPIRIN
chronic toxicity -dose -Cx presentation -Pathology |
dose: 3+ gm/day
Cx: HA, dizzy, tinnitus, N/V/D, confusion, drowsy, convulsions, coma Path morphology: acute erosive gastritis due to ulcertaion, petechiae (COX inhibition), renal papillary necrosis |
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Six Major outdoor air pollutants
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OZONE
Nitrogen oxides sulfur dioxide particulates CO lead |
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Who is at highest risk for outdoor air pollutants?
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kids
asthmatics chronic heart/lung Dx patients |
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effect of most outdoor air pollutants
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Respiratory tract irritants
|
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sources of lead poisoning
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contaiminates air, soil, house dust, ceramics, food and drink
|
|
lead absorption is enhanced by:
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CA/Fe/Zn deficiencies
greater in kids (80-85% in bone/teeth, 5-10% in blood, rest in soft tissue) |
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Lead toxicity
organ/system involved (effect) |
1) BLOOD (hypochromic anemia via inhibition of iron incorporation into heme)
2) CNS (inverse correlation betwen IQ and blood lead level) 3) Bone, nervous system (competes w/ Ca) 4) GI tract (lead colic) 5) Kidneys (renal failure) |
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Agricultural hazards
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INSECTICIDES (organochorines like DDT, organophosphates, carbamates)
HERBICIDES (dioxins, eg: agent orange) NATURAL TOXINS (mycotoxins, eg aflatoxin B1, phytotoxins, animal toxins like saxitoxin) |
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Carbon Monoxide
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colorless, odorless gas byproduct of gasoline, oil, coal, wood, natural gas and cigarette smoke
200x affinifity for Hb as O2 and impairs release of O2 from Hb HA, dizzy, loss motor fxn, coma 900 deaths/ year in US |
|
Radon:
-source? -effect? -incidence of toxicity? |
radioactive gas decay product of uranium
decay products emit alpha radiation associated with lung cancer in miners 10,000 lung cancer cases per year in US |
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Industrial sources of lead
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beatteries
alloys exterior lead paint ammunition mining smelting spray painting recycling radiator repairs |
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Environmental sources of lead
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air (leaded gasoline)
soil (exterior lead paint) water (lead plumbing) house dust (interior lead paint) ceramics (lead glaze) food/ soft drinks (lead solder) moonshine |
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insecticides
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ORGANOCHLORINES: ddt bioaccumultaes, chlordane and lymphomas?
ORGANOPHOSPHAGES (neurotoxins) irreversibly inhibit cholinesterases (40% of farm workers) CARBAMATES (reversibly inhibit cholinesterase) |
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Agent Orange is a:
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DIOXIN (an Herbicide)
-increased incidence of leukemia, lymphoma, sarcoma -immunosuppresive, teratogenic and carcinogenic in lab animals |
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Natural Toxins
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mycotoxins (aflatoxin B1 and liver cancer)
Phytotoxins (cycasin and ALS) animal toxins (saxitoxin and paralytic shellfish poisoning) |
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ETOH is involved in what % of traffic deaths?
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40%
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Types of Physical hazards
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Mechanical
Thermal Electical Pressure |
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Types of Thermal injuries
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Burns
Hypothermia Hyperthermia |
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Thermal injury- burns:
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5000 deaths/yr in US
vary in severity (partial/ full thickness) shock at 20% BSA >50% BSA = FATAL Shock, inhalation injury, secondary infection, hypermetabolic state |
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Rule of 9
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used to guage % BSA involved in burn
Head = 9% (18% in infants) neck = 1% arm = 9% each trunk = 18% each side leg = 18% (13.5% infant) each total = 100% BSA |
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Partial thickness burns
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1st degree (epidermis only)
2nd degree |
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Full thickness burns
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3rd and 4th degree
-dry, white or charred -total destruction of epidermis, dermis |
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mechanism of Shock due to Thermal burn
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@ 20% BSA burned
increased local interstitial osmotic pressure and increased vascular permeability |
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mechanims/ Cx features of inhalation injury due to thermal injury
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direct head and gas toxins
may be delayed 24-48 hours |
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Complications of Thermal burns
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Shock
inhalation injury Secondary infection hypermetabolic state (40% BSA doubles metabolic rate) |
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Manifestations of Hyperthermia
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Head cramps
Heat exhaustion Heat stroke |
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most common manifestation of hyperthermia
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HEAT CRAMPS
voluntary muscle cramps d/t electrolyte imbalance d/t exertional sweating normal core temp |
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characteristics of HEAT EXHAUSTION
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prostration and collapse d/t hypovolumia, d/t water depletion, d/t sweating with inadequate fluid replacement
Normal core temp heat stroke |
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characteristics of HEAT STROKE
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failure of thermoregulation at high ambient temperature and humidity
-elderly, militar recruits, athletes at risk -loss of sweating results in ELEVATED CORE TEMP, vasodilation and reduced circulating blood volume -myonecrosis, arrythmia, DIC -50% mortality if T > 106 F |
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Hypothermia
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loss of thermoregulation aggravated by humity and ethanol (cutaneous vasodilation)
|
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systemic effects of hypothermia
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at T < 90F there is LOC, bradycardia, AFib
|
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local effects of hypothermia
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direct: crystallization of water with increased salt
indirect: vasoconstriction and permeability (edema, ischemia) |
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Electrical injuries
low vs high voltage |
low voltage - cause vFib
high voltage- cause paralysis of medullary centers, asystole |
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Result of electrical injuries
|
no effect, sudden death, thermal burns
|
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type of electrical current that causes tetany
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AC (vs. DC)
|
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Effects of high altitude (4000m +)
|
Pulmonary Edema (HAPE)
Cerebral EDEMA (HACE) |
|
Examples of Barotrauma/decompression sickness
|
Rapid decompression
CAGE bends, chokes, staggers Caissons disease of bone |
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Primary causes of malnutrition
|
Ignorance
Poverty Self-imposed |
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Secondary causes of malnutrition
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Malabsorption
Impaired utilization/storage Excess losses Increased BMR |
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Protein Energy Malnutrition
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inadequate intake of protein and calories
25% of kids in dvpg world -SOMATIC (skeletal muscle) depleted in MARASMUS) -VISCERAL (organs, eg liver) depleted in KWASHIORKOR |
|
Dx of Protein energy malnutrition
|
body wt for height
fat stores (skin fold thickness) muscle mass (midarm circum) serum proteins (reflect visceral stores) |
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MARASMUS
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severe reduction in cals
<60% normal body weight growth retardation, muscle loss, fat loss (wasted extremities, large head) -preserved albumin -anemia, immune deficiencies (infection) |
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KWASHIORKOR
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protein deprivation (CHO diet)
60-80% normal body weight severe loss visceral stores (LOW ALBUMIN) leads to edema relative sparing of fat and muscle stores skin changes (flaky paint), hair changes, fatty liver, loss of appetite, apathy, listlessness, immune deficiency (infections) |
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Secondary cuases of Protein Energy malnutrition
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cancer, AIDS, chronic GI disease, bedridden patients
signs: depletion of subcutaneous fat, muscle wasting, sacral/pedal edema |
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Anorexia nervosa
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amenorrhea, reduced bone density, anemia, hypoalbuminemia at risk SCD
|
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Bulimia
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less amenorrhea, at risk for aspiration, esophageal/gastric rupture, SCD
|
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obesity (BMI > 30)
related diseases: |
diabetes, hypertension, CAD, osteoarthritis, hypoventilation, pancreatitis, NASH, ischemic stroke, venous thrombosis)
|
|
% of adults in US-
OVERWEIGHT: OBESE: |
35 % overweight
30% obese |
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Dx obesity:
|
BMI:
normal: 18.5-24.9 kg/m^2 overweight = 25-29.9 kg/m^2 obese: >30kg/m^2 skin fold measurements body circumferences (waist to hip ratio) |
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SYNDROME X
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abdominal obesity
insulin resistance increased TAG decreased HDL hypertension coronary artery disease |
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etiology of syndrome X
|
disorder of energy balance
genetic environmental and psychological factors neurohumoral mechanism -afferent system (humoral signals from fat, pancreas, stomach) -CPU (hypothalamus) -effector system (feeding behavior and energy expenditures) |
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Leptin
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cytokine secreted by adipocytes
crosses BBB and binds leptin receptors inhibits anabolic circuits and triggers catabolic circuits reduces food intake and promotes energy expenditure Leptin deficient mice are morbidly obese elevated blood levels (low CSF levels) in most obses persons |
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6 known genetic causes of obesity
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Leptin receptor, POMC and PC1 (4)
-autosomal recessive, rare -hyperphagia, childhood onset massive obesity Melanocortin receptor (1) -common (5-8% obese persons) -inability to stimulate energy consumption SIM1 transcription factor (1) -essential factor for formation of second order Leptin enurons |
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these reduce risk of fatal MI and sudden cardiac death
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Omega-3 Fatty acids
|
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restricting sodium has beneficial effect on what?
|
BP
|
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dietary fiber prevents what disease?
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diverticulosis
|
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fruits and veggies with limited meat and processed foods lowers risk of?
|
MI
|
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calorie restriction, increases what?
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lifespan
|
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fruits and vegetables lower risk of cancer via???
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anticarcinogenic effect of carotenoids (vit A)?
|
|
High animal fat and low fiber diets are associated with what type of cancer?
-supposed mechanism? |
COLON CANCER
-increased bile acids alter intestinal flora -intestinal floral alter bile acids -altered bile acids carcinogenic or promotor |
|
why might a high fiber diet be protective against colon cancer?
|
decreased transit time
certain fibers bind carcinogens |
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Pneumoconioses
|
non-neoplastic LUNG RXN to inhalation of mineral dusts in workplace
now includes rxns to organic and inorganic particulates, fumes and vapors |
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Pathogenesis of Pneumoconioses
|
-amt of dust retained (concentration, duration of exposure, clearance mechanisms)
-size/shape of particles (1-5micrometers most dangerous) -particle solubility and reactivity (inflamm/immun response) -other irritants (cig. smoke) |
|
Coal Workers' Penumoconisosis
|
decreased incidence with dust reduction
<10% develop PMF (pulmonary hypertension and cor pulmonale) NO increased TB susceptibility NO predisposition to lung cancer (unless smokers) INCREASED INCIDENCE chronic bronchitis, emphysema |
|
morphology of CWP
asymptomatic anthracosis: |
asymptomatic anthracosis:
inhaled carbon engulfed by M0s in CT and lymphoid tissue) |
|
morphology of simple CWP
|
coal macules and nodules
upper lobes most, upper lower lopes at respiratory bronchioles |
|
morphology of complicated CWP (PMF)
|
multiple massive (up to 10 cm blackened scars)
|
|
most prevalent chronic occupational disease in the world
|
SILICOSIS
|
|
SILICOSIS results from:
|
inhalation of crystalline silicon dioxide (silica)
most prevalent chronic occupational disease in the world (sandblasters, mine workers) |
|
characteristics of Silicosis
|
slowly progressive, nodular, fibrosing (over decades)
less commonly, acute accumulation of lipoproteinaceous material in alveoli (mos to yrs) |
|
Pathogenesis of Silicosis
|
crystalline (more fibrogenic) or amorphous silica
-engulfed by M0s -release of mediators (eg TNF) -amplification of inflammatory response |
|
early stages of Silicosis
|
nodules in upper lung zones containing BIREFRINGENT silica
|
|
later stages of silicosis
|
-coalesced hard collagenous scars
-cavitation -eggshell calcification -PMF |
|
clinical course of silicosis
|
-fine nodularity in upper lung zones on chest xray
-shortness of breath (PMF) -increased TB susceptibility -carcinogenic? |
|
Asbestos related diseases
(involve chrystalline hydrated silicates that form fibers) |
Occupation:
-fibrous pleural plaques -pleural effusions -interstitial fibrosis (asbestosis) -lung cancer -mesotheliomas -extrapulmonary neoplasms Increased incidence of asbestos related cancer in family members |
|
Pathogenesis of Asbestos related diseases determined by:
|
concentration, side, shape and solubility of fibers
longer fibers more pathogenic SERPENTINE (most common, less pathogenic, soluble) AMPHIBOLE (more pathogenic, deeper penetration, only exposure correlated with meothelioma) |
|
Oncogenicity of Aspestos
|
initiator and promoter activity
reactive free radicals adsorbed toxic chemicals (synergy w/ tobacco smoke ~5x to 55x risk) |
|
Morphology of asbestosis
|
-lower lobes, subpleural around bronchioles, ducts
-diffuse interstitial fibrosis with honeycombing (pulmonary hypertension, core pulmonale) -asbestos bodies (golden brown beaded rods) |
|
Morphology of Pleural plaques (most common asbestos disease)
|
well circumcribed collagen plaques with Ca
no asbestos bodies |
|
Lung cancer (risk increase associated with smoking)
|
5x risk increased with smoking
|
|
Meothelioma (risk increase with smoking?
|
1000x risk
|
|
clinical course of Asbestosis
|
-delayed 10 or 20 yrs after exposure
(dyspnea on exertion to rest, cough with sputum production) -CXR irregular linear densities lower lung lobes, plaques -may progress to respiratory failure, cor pulmonale, death |
|
hypersensitivity pneumonitis
|
hypersensitivity of alveoli to inhaled organic dusts (allergic alveolitis)
-thermophilic bacteria (actinomycetes, Farmer's lung) -true fungi -animal proteins (pigeon breeder's lung/bird fancier's disease) -bacterial products |
|
immune-mediated pathogenesis in hypersensitivity pneumonitis
|
-increased chemokines in BAL specimins
-increased T cells in BAL speciments -specific Abs in serum -complement and immunoglobulins in vessel walls -noncaseating granulomas in most |
|
morphology of HP (hypersensitivity pneumonitis)
|
interstitial pneumonitis (lymphocytes, plasma cells M0s)
-noncaseating granulomas -interstitial fibrosis and obliterative bronchiolitis -intra-alveolar infiltrate |
|
Cx features of HP (hypersensitivity pneumonitis)
|
-acute attacks of fever, dyspnea, cough, leukocytosis, 4 to 6 hours after exposure
-diffuse and nodular infiltrates on chest radiograph -acute restrictive disorder on PFTs -progression with protracted exposure to respiratory failure, dyspnea, cyanosis, decreased TLC and compliance |